Synthetic phospholipid used in liposomes and lipid bilayers to study biological membranes. It is also a major constituent of PULMONARY SURFACTANTS.
A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES
An ANGIOTENSIN II analog which acts as a highly specific inhibitor of ANGIOTENSIN TYPE 1 RECEPTOR.
A synthetic prostaglandin E analog that protects the gastric mucosa, prevents ulceration, and promotes the healing of peptic ulcers. The protective effect is independent of acid inhibition. It is also a potent inhibitor of pancreatic function and growth of experimental tumors.
11 beta,18,21-Trihydroxypregn-4-ene-3,20-dione.
An analog of desoxycorticosterone which is substituted by a hydroxyl group at the C-18 position.
The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.
A purine that is an isomer of ADENINE (6-aminopurine).
2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system.
Simple amine found in the brain. It may be modulator of sympathetic functions. Its derivatives are adrenergic agonists and antagonists. It is also used in chemical industry.
A sulfhydryl compound that is used to reduce the incidence of hemorrhagic cystitis associated with certain chemotherapeutic agents. Mesna is converted to a free thiol compound in the kidney, where it binds to and inactivates acrolein and other urotoxic metabolites of ifosfamide and cyclophosphamide, thereby reducing their toxic effects on the urinary tract during urinary excretion. (NCI04)
A synthetic precursor of norepinephrine that is used in the treatment of PARKINSONIAN DISORDERS and ORTHOSTATIC HYPOTENSION.
An amino acid formed in vivo by the degradation of dihydrouracil and carnosine. Since neuronal uptake and neuronal receptor sensitivity to beta-alanine have been demonstrated, the compound may be a false transmitter replacing GAMMA-AMINOBUTYRIC ACID. A rare genetic disorder, hyper-beta-alaninemia, has been reported.
A synthetic analogue of nucleoside uridine lacking a ring nitrogen in the 3-position. 3-deazauridine inhibits cytidine synthase, thereby reducing intracellular levels of cytidine and deoxycytidine and disrupting DNA and RNA synthesis. This agent may trigger apoptosis and enhance differentiation of neoplastic cells.(NCI04)
An antilipemic agent which lowers cholesterol, triglycerides, serum beta-lipoproteins and phospholipids. It acts by interfering with the enzymatic steps involved in the conversion of acetate to hydroxymethylglutaryl coenzyme A as well as inhibiting the activity of HYDROXYMETHYLGLUTARYL COA REDUCTASES which is the rate limiting enzyme in the biosynthesis of cholesterol.
An inhibitor of glutamate decarboxylase. It decreases the GAMMA-AMINOBUTYRIC ACID concentration in the brain, thereby causing convulsions.
An aminobenzoic acid isomer that combines with pteridine and GLUTAMIC ACID to form FOLIC ACID. The fact that 4-aminobenzoic acid absorbs light throughout the UVB range has also resulted in its use as an ingredient in SUNSCREENS.
One of the POTASSIUM CHANNEL BLOCKERS with secondary effect on calcium currents which is used mainly as a research tool and to characterize channel subtypes.
One of the FURANS with a carbonyl thereby forming a cyclic lactone. It is an endogenous compound made from gamma-aminobutyrate and is the precursor of gamma-hydroxybutyrate. It is also used as a pharmacological agent and solvent.
hydroxy derivative of butyric acid substituted at the gamma, or 4 position; intermediate in the metabolism of gamma-aminobutyric acid (GABA).
Substances found in many plants, containing the 4-hydroxycoumarin radical. They interfere with vitamin K and the blood clotting mechanism, are tightly protein-bound, inhibit mitochondrial and microsomal enzymes, and are used as oral anticoagulants.
Tryptamine substituted with two hydroxyl groups in positions 5 and 6. It is a neurotoxic serotonin analog that destroys serotonergic neurons preferentially and is used in neuropharmacologic research.
Tryptamine substituted with two hydroxyl groups in positions 5 and 7. It is a neurotoxic serotonin analog that destroys serotonergic neurons preferentially and is used in neuropharmacology as a tool.
A polyunsaturated long-chain fatty acid with a 20-carbon backbone and 5 double bonds, originating from the 3rd, 6th, 9th, 12th and 15th positions from the methyl end.
A 20-carbon unsaturated fatty acid containing 4 alkyne bonds. It inhibits the enzymatic conversion of arachidonic acid to prostaglandins E(2) and F(2a).
An aromatic amino acid with antidepressant activity. In vivo, oxitriptan (or 5-hydroxytryptophan) is converted into 5-hydroxytryptamine (5-HT or serotonin) as well as other neurotransmitters. Oxitriptan may exert its antidepressant activity via conversion to serotonin or directly by binding to serotonin (5-HT) receptors within the central nervous system (CNS). Endogenous oxitriptan is produced from the essential amino acid L-tryptophan. The exogenous therapeutic form is isolated from the seeds of the African plant Griffonia simplicifolia.
Serotonin derivative proposed as potentiator for hypnotics and sedatives.
The hydrochloride salt form of ticlopidine, a thienopyridine derivative with anticoagulant property. Ticlopidine hydrochloride irreversibly inhibits adenosine-diphosphate (ADP)-induced platelet-fibrinogen binding by binding to the glycoprotein (GP) IIb/IIIA complex, one of the two purinergic receptors activated by ADP. Inhibition of the receptor activation causes the inhibition of adenylyl cyclase, results in decreased levels of cyclic adenosine monophosphate and thereby interferes with platelet membrane function and subsequent, platelet-platelet interaction, release of platelet granule constituents and prolongation of bleeding time.
A synthetic lysine derivative with antifibrinolytic activity. Aminocaproic acid competitively inhibits activation of plasminogen, thereby reducing conversion of plasminogen to plasmin (fibrinolysin), an enzyme that degrades fibrin clots as well as fibrinogen and other plasma proteins including the procoagulant factors V and VIII. Aminocaproic acid competitively reduces the conversion of plasminogen to plasmin by plasminogen activators. It directly inhibits proteolytic activity of plasmin, but higher doses are required than are needed to reduce plasmin formation. Aminocaproic acid is used in the treatment of hemorrhage and prophylactically against hemorrhage, including hyperfibrinolysis-induced hemorrhage and postsurgical hemorrhage.
A synthetic analogue and nicotinamide antagonist with cytotoxic properties, 6-Aminonicotinamide forms an abnormal NAD (ubiquitous metabolic pathway coenzyme) analog that inhibits NAD-dependent enzyme activity associated with ATP production. 6-Aminonicotinamide impairs cartilage formation, may have teratogenic effects, and enhances the effect of radiation and cisplatin treatment (formation of platinum-DNA complexes). (NCI04)
A thiopurine-derivative antimetabolite with antineoplastic and immunosuppressive activities. Produced through the metabolism of mercaptopurine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT), mercaptopurine metabolites 6-thioguanosine-5'-phosphate (6-thioGMP) and 6-thioinosine monophosphate (T-IMP) inhibit nucleotide interconversions and de novo purine synthesis, thereby blocking the formation of purine nucleotides and inhibiting DNA synthesis. This agent is also incorporated into DNA in the form of deoxythioguanosine, which results in the disruption of DNA replication. In addition, mercaptopurine is converted to 6-methylmercaptopurine ribonucleoside (MMPR) by 6-thiopurine methyltransferase; MMPRs are also potent inhibitors of de novo purine synthesis. (NCI04)
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
An antiseptic with mild fungistatic, bacteriostatic, anthelmintic, and amebicidal action. It is also used as a reagent and metal chelator, as a carrier for radio-indium for diagnostic purposes, and its halogenated derivatives are used in addition as topical anti-infective agents and oral antiamebics.
A clinical syndrome with acute abdominal pain that is severe, localized, and rapid in onset. Acute abdomen may be caused by a variety of disorders, injuries, or diseases.
An involuntary muscular contraction involving a muscle of the abdomen or of a hollow organ within the abdomen.
An abnormal enlargement or swelling in the abdomen.
New abnormal growth of tissue in the ABDOMEN.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Abetalipoproteinemia typically presents in infancy with failure to thrive, diarrhea, vomiting, and malabsorption of fat. Hematologic manifestations may include acanthocytosis (irregularly spiculated erythrocytes), anemia, reticulocytosis, and hemolysis with resultant hyperbilirubinemia. Malabsorption of fat-soluble vitamins (A, D, E, and K) can result in an increased international normalized ratio (INR). Untreated individuals may develop atypical pigmentation of the retina that may present with progressive loss of night vision and/or color vision in adulthood. Neuromuscular findings in untreated individuals including progressive loss of deep tendon reflexes, vibratory sense, and proprioception; muscle weakness; dysarthria; and ataxia typically manifest in the first or second decades of life.
Any abnormality, anatomical or biochemical, evident at birth or during the neonatal period.
Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.
Congenital abnormalities that affect more than one organ or body structure.
Chemical substances that interrupt pregnancy after implantation.
Non-steroidal chemical compounds with abortifacient activity.
Steroidal compounds with abortifacient activity.
A pregnancy that ends at a stage in which the fetus is incapable of surviving on its own, defined as the spontaneous loss of a fetus before the 20th week of pregnancy.
Three or more consecutive spontaneous abortions.
Premature loss of PREGNANCY in which not all the products of CONCEPTION have been expelled.
Any type of abortion, induced or spontaneous, that is associated with infection of the UTERUS and its appendages. It is characterized by FEVER, uterine tenderness, and foul discharge.
UTERINE BLEEDING from a GESTATION of less than 20 weeks without any CERVICAL DILATATION. It is characterized by vaginal bleeding, lower back discomfort, or midline pelvic cramping and a risk factor for MISCARRIAGE.
Premature expulsion of the FETUS in animals.
Placental separation from the uterus with bleeding (concealed or vaginal) before fetal birth, with or without maternal/fetal compromise. (reVITALize)
Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection.
A congenital abnormality resulting in the absence of an anatomical structure.
Infection of the cornea by an ameboid protozoan which may cause corneal ulceration leading to blindness.
Atrophy of the stratum spinosum layer of the epidermis due to disruption of the intercellular attachments between keratinocytes.
A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder.
A cardioselective beta-1 adrenergic antagonist with little effect on the bronchial receptors. The drug has stabilizing and quinidine-like effects on cardiac rhythm, as well as weak inherent sympathomimetic action.
Acetylated sulfone that is slowly metabolized to give long-term, low blood levels of DAPSONE. It has antimicrobial and antimalarial action, but is mainly used as a depot leprostatic agent.
A 4-hydroxycoumarin derivative with anticoagulant activity. As a vitamin K antagonist, acenocoumarol inhibits vitamin K epoxide reductase, thereby inhibiting the reduction of vitamin K and the availability of vitamin KH2. This prevents gamma carboxylation of glutamic acid residues near the N-terminals of the vitamin K-dependent clotting factors, including factor II, VII, IX, and X and anticoagulant proteins C and S. This prevents their activity and thus thrombin formation. Compared to other coumarin derivatives, acenocoumarol has a short half-life.
A phenothiazine derivative with depressant effect on the central nervous system. Acepromazine acts as a dopamine receptor antagonist in the CNS, thereby causing sedation, muscular relaxation and a reduction in spontaneous activity. Its fast-acting neuroleptic effect with low toxicity is of particular value in veterinary medicine.
The maleate salt of acepromazine, a phenothiazine derivative with depressant effect on the central nervous system. Acepromazine acts as a dopamine receptor antagonist in the CNS, thereby causing sedation, muscular relaxation and a reduction in spontaneous activity. Its fast-acting neuroleptic effect with low toxicity is of particular value in veterinary medicine.
A p-aminophenol derivative with analgesic and antipyretic activities. Although the exact mechanism through which acetaminophen exert its effects has yet to be fully determined, acetaminophen may inhibit the nitric oxide (NO) pathway mediated by a variety of neurotransmitter receptors including N-methyl-D-aspartate (NMDA) and substance P, resulting in elevation of the pain threshold. The antipyretic activity may result from inhibition of prostaglandin synthesis and release in the central nervous system (CNS) and prostaglandin-mediated effects on the heat-regulating center in the anterior hypothalamus.
Salt or ester form of acetic acid. Acetate is the most common building block for biosynthesis, such as fatty acids.
Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.
A sulfonamide derivative with diuretic, antiglaucoma, and anticonvulsant properties. Acetazolamide is a non-competitive inhibitor of carbonic anhydrase, an enzyme found in cells in the proximal tube of the kidney, the eye, and glial cells. Inhibition of this enzyme in the kidney prevents excretion of hydrogen, leading to increased bicarbonate and cation excretion and increased urinary volume, which results in an alkaline diuresis. Acetazolamide reduces the concentration of bicarbonate, resulting in a decreased synthesis of aqueous humor in the eye, thereby lowering intraocular pressure. Although its mechanism of action is unknown, acetazolamide has anti-convulsant properties resulting from indirect effects secondary to metabolic acidosis or direct effects on neuronal transmission. Acetazolamide also produces respiratory stimulant effects in response to changes to both carbon dioxide and oxygen tension levels within the lungs.
A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1-hydrohexamide.
A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis.
Acetylation involves the covalent linkage of an acetyl group into an organic molecule.
An acetic acid ester of CARNITINE that facilitates movement of ACETYL COA into the matrices of mammalian MITOCHONDRIA during the oxidation of FATTY ACIDS.
A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.
Any substance that inhibits acetylcholinesterase (AchE), an enzyme that breaks down acetylcholine (Ach) in the synaptic cleft. Inhibition of acetylcholinesterase results in an increase in the level and duration of action of acetylcholine.
A synthetic N-acetyl derivative of the endogenous amino acid L-cysteine, a precursor of the antioxidant enzyme glutathione. Acetylcysteine regenerates liver stores of glutathione. This agent also reduces disulfide bonds in mucoproteins, resulting in liquification of mucus. Some evidence suggests that acetylcysteine may exert an anti-apoptotic effect due to its antioxidant activity, possibly preventing cancer cell development or growth. In addition, acetylcysteine has inhibited viral stimulation by reactive oxygen intermediates, thereby producing antiviral activity in HIV patients. (NCI04)
Cardioactive derivatives of lanatoside A or of DIGITOXIN. They are used for fast digitalization in congestive heart failure.
Alpha- or beta-acetyl derivatives of DIGOXIN or lanatoside C from Digitalis lanata. They are better absorbed and longer acting than digoxin and are used in congestive heart failure.
A naturally occurring component of bacterial cell walls that has the capacity to activate macrophages.
A major metabolite of PROCAINAMIDE. Its anti-arrhythmic action may cause cardiac toxicity in kidney failure.
An agent used as a substrate in assays for cholinesterases, especially to discriminate among enzyme types.
A lack of HYDROCHLORIC ACID in GASTRIC JUICE despite stimulation of gastric secretion.
A rare group of disorders characterized by defective development of bones and cartilage.
Achondroplasia is the most common cause of disproportionate short stature. Affected individuals have rhizomelic shortening of the limbs, macrocephaly, and characteristic facial features with frontal bossing and midface retrusion. In infancy, hypotonia is typical, and acquisition of developmental motor milestones is often both aberrant in pattern and delayed. Intelligence and life span are usually near normal, although craniocervical junction compression increases the risk of death in infancy. Additional complications include obstructive sleep apnea, middle ear dysfunction, kyphosis, and spinal stenosis.
An abnormality of the balance or maintenance of the balance of acids and bases in bodily fluids, resulting in an abnormal pH.
A pathologic condition of acid accumulation or depletion of base in the body. The two main types are RESPIRATORY ACIDOSIS and metabolic acidosis, due to metabolic acid build up.
Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as DIABETES MELLITUS; LEUKEMIA; or LIVER FAILURE.
A group of genetic disorders of the KIDNEY TUBULES characterized by the accumulation of metabolically produced acids with elevated plasma chloride, hyperchloremic metabolic ACIDOSIS. Defective renal acidification of URINE (proximal tubules) or low renal acid excretion (distal tubules) can lead to complications such as HYPOKALEMIA, hypercalcinuria with NEPHROLITHIASIS and NEPHROCALCINOSIS, and RICKETS.
A condition in which the blood pH is less than normal, secondary to impaired gas exchange.
A sodium fluoride solution, paste or powder, which has been acidulated to pH 3 to 4 and buffered with a phosphate. It is used in the prevention of dental caries.
Infections with bacteria of the genus ACINETOBACTER.
A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors.
A chronic eruption of fibrous papules that develop and fuse to form a thick sclerotic, hypertrophic band at a site of deep folliculitis, usually along the posterior hairline of the scalp. It is most commonly seen in men of African descent.
A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM plants. It activates VOLTAGE-GATED SODIUM CHANNELS. It has been used to induce ARRHYTHMIAS in experimental animals and it has antiinflammatory and antineuralgic properties.
A non-neoplastic or neoplastic disorder affecting the acoustic nerve.
Deficiency of a coagulation factor that is not caused by genetic alterations. Causes include vitamin K deficiency, amyloidosis, and severe liver disease.
A syndrome resulting from the acquired deficiency of cellular immunity caused by the human immunodeficiency virus (HIV). It is characterized by the reduction of the Helper T-lymphocytes in the peripheral blood and the lymph nodes. Symptoms include generalized lymphadenopathy, fever, weight loss, and chronic diarrhea. Patients with AIDS are especially susceptible to opportunistic infections (usually pneumocystis carinii pneumonia, cytomegalovirus (CMV) infections, tuberculosis, candida infections, and cryptococcosis), and the development of malignant neoplasms (usually non-Hodgkin lymphoma and Kaposi sarcoma). The human immunodeficiency virus is transmitted through sexual contact, sharing of contaminated needles, or transfusion of contaminated blood.
3,6-Diamino-10-methylacridinium chloride mixt. with 3,6-acridinediamine. Fluorescent dye used as a local antiseptic and also as a biological stain. It intercalates into nucleic acids thereby inhibiting bacterial and viral replication.
The eight disorders comprising the FGFR-related craniosynostosis spectrum are Pfeiffer syndrome, Apert syndrome, Crouzon syndrome, Beare-Stevenson syndrome, FGFR2-related isolated coronal synostosis, Jackson-Weiss syndrome, Crouzon syndrome with acanthosis nigricans (AN), and Muenke syndrome (isolated coronal synostosis caused by the p.Pro250Arg pathogenic variant in FGFR3). Muenke syndrome and FGFR2-related isolated coronal synostosis are characterized only by uni- or bicoronal craniosynostosis; the remainder are characterized by bicoronal craniosynostosis or cloverleaf skull, distinctive facial features, and variable hand and foot findings.
An inflammatory skin condition affecting children. It is often associated with Epstein-Barr virus infection, hepatitis B infection or cytomegalovirus infection. It is characterized by the presence of cutaneous rashes and patches on the palms and soles. The trunk is not affected.
Overgrowth of the stratum corneum characterized by flesh-coloured or slightly pigmented smooth or warty papules on the upper surface of hands and feet.
Acromegaly is a condition resulting from overproduction of growth hormone by the pituitary gland in persons with closed epiphyses, and consists chiefly in the enlargement of the distal parts of the body. The circumference of the skull increases, the nose becomes broad, the tongue becomes enlarged, the facial features become coarsened, the mandible grows excessively, and the teeth become separated. The fingers and toes grow chiefly in thickness.
A natural alkaloid with an acridine structure isolated from the bark of the plant Acronychia baueri (Australian scrub ash) with antineoplastic properties. Acronycine appears to alkylate DNA and interfere with DNA replication. (NCI04)
A syndrome characterized by abnormal secretion of adrenocorticotrophic hormone in conjunction with neoplastic growth occurring anywhere in the body. The most common associations are tumors of the bronchus (oat cell or carcinoid), thymic tumors (epithelial or carcinoid), and pancreatic endocrine tumor. (DeVita et al. Cancer, p 1364. 4th edition. Lippincott)
An extract from calf blood containing inorganic salts, amino acids, polypeptides and purines, but no proteins nor antigenic substances or blood group characteristics. Its exact composition is unknown. It has been proposed as a radiation-protective agent.
A disease characterized by suppurative and granulomatous lesions in the respiratory tract, upper alimentary tract, skin, kidneys, joints, and other tissues. Actinobacillus lignieresii infects cattle and sheep while A. equuli infects horses and pigs.
Infections with bacteria of the genus ACTINOBACILLUS.
An infectious process caused by actinomycetales which is an order of Actinobacteria.
An infectious process caused by bacteria of the Actinomyces species. It is characterized by the formation of purulent and painful abscesses in the mouth, lungs and gastrointestinal tract.
A form of ACTINOMYCOSIS characterized by slow-growing inflammatory lesions of the lymph nodes that drain the mouth (lumpy jaw), reddening of the overlying skin, and intraperitoneal abscesses.
Carbon that has been treated to create small, low-volume pores that increase the surface area available for adsorption.
Acute hepatitis resulting from ingestion of alcohol.
Atopic conjunctivitis that is of relatively short duration and that has a rapid onset.
Acute inflammation of the bronchioles usually caused by the respiratory syncytial virus.
Any disease of sudden onset AND/OR short duration
An acute inflammatory process affecting the larynx. It is caused by bacteria, viruses, or vocal strain. Signs and symptoms include sore throat, cough, swallowing difficulties, and hoarseness.
An acute inflammatory process that affects the tissues that surround and support the teeth.
An acute and painful inflammatory process that affects the pharynx. It is usually caused by viruses and less often bacteria. Signs and symptoms include discomfort on swallowing, low-grade fever, headache, and earache.
An early local inflammatory reaction to insult or injury that consists of fever, an increase in inflammatory humoral factors, and an increased synthesis by hepatocytes of a number of proteins or glycoproteins usually found in the plasma.
An acute inflammation of the tonsils caused by viruses or bacteria. Signs and symptoms include fever, enlargement of the tonsils, difficulty swallowing, and enlargement of the regional lymph nodes.
Ischemia of the intestine that is rapid in onset.
Extensive and rapid death of parenchymal cells in the LIVER, often due to exposure to toxic materials. It is characterized by a soft, flabby, yellow-brown wrinkled, and shrunken liver. It was called ""acute yellow atrophy"".
A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.
A condition of fainting spells caused by heart block, often an atrioventricular block, that leads to BRADYCARDIA and drop in CARDIAC OUTPUT. When the cardiac output becomes too low, the patient faints (SYNCOPE). In some cases, the syncope attacks are transient and in others cases repetitive and persistent.
A long-standing and persistent diminished production of adrenocortical hormones due to a disorder originating within the adrenal glands.
condensation product of adenosine and phosphoric acid; a nucleotide found among the hydrolysis products of all nucleic acids.
A common cancer characterized by the presence of malignant glandular cells. Morphologically, adenocarcinomas are classified according to the growth pattern (e.g., papillary, alveolar) or according to the secreting product (e.g., mucinous, serous). Representative examples of adenocarcinoma are ductal and lobular breast carcinoma, lung adenocarcinoma, renal cell carcinoma, hepatocellular carcinoma (hepatoma), colon adenocarcinoma, and prostate adenocarcinoma.
A morphologic variant of adenocarcinoma. It is characterized by the presence of a papillary growth pattern. Representative examples include thyroid gland papillary carcinoma, invasive papillary breast carcinoma, and ovarian serous surface papillary adenocarcinoma.
A benign neoplasm composed of glandular and fibrous tissues, with a relatively large proportion of glands. (Stedman, 25th ed)
An adenoma characterized by an oncocytic, often papillary, epithelial component, dense lymphoid stroma, and cystic spaces. It occurs primarily in the parotid gland, and is the second most common benign parotid salivary gland tumor. A strong association with smoking has been reported. It typically presents as a painless swelling in the lower portion of the parotid gland.
A neoplasm arising from the epithelium. It may be encapsulated or non-encapsulated but non-invasive. The neoplastic epithelial cells may or may not display cellular atypia or dysplasia. In the gastrointestinal tract, when dysplasia becomes severe it is sometimes called carcinoma in situ. Representative examples are pituitary gland adenoma, follicular adenoma of the thyroid gland, and adenomas (or adenomatous polyps) of the gastrointestinal tract.
An epithelial neoplasm of the anterior pituitary gland in which the neoplastic cells stain positive with basic dyes.
An epithelial neoplasm of the anterior pituitary gland in which the neoplastic cells do not stain with acidic or basic dyes.
An epithelial neoplasm of the anterior pituitary gland in which the neoplastic cells stain positive with acidic dyes.
A low grade malignant neoplasm characterized by the presence of a benign epithelial component (tubular and cleft-like glands) and a low grade sarcomatous component that contains varying amounts of fibrous and smooth muscle tissues. In a minority of cases, the sarcomatous component contains heterologous elements including striated muscle, cartilage, and fat. It occurs in the uterine corpus, ovary, fallopian tube, cervix, and vagina. It may recur and in a minority of cases may metastasize to distant anatomic sites.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
A second messenger molecule comprised of an adenine ribonucleotide bearing a phosphate group bound to the oxygen molecules at the 3' and 5' positions of the sugar moiety. Cyclic AMP, which is synthesized from ATP by the intracellular enzyme adenylate cyclase, modulates the activity of several hormone-dependent signal transduction pathways.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
An adenine nucleotide comprised of three phosphate groups esterified to the sugar moiety, found in all living cells. Adenosine triphosphate is involved in energy production for metabolic processes and RNA synthesis. In addition, this substance acts as a neurotransmitter. In cancer studies, adenosine triphosphate is synthesized to examine its use to decrease weight loss and improve muscle strength.
An infectious process caused by adenovirus. The virus may cause respiratory illness, conjunctivitis, gastroenteritis, and cystitis.
Respiratory and conjunctival infections caused by 33 identified serotypes of human adenoviruses.
5'-Adenylic acid, monoanhydride with imidodiphosphoric acid. An analog of ATP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It is a potent competitive inhibitor of soluble and membrane-bound mitochondrial ATPase and also inhibits ATP-dependent reactions of oxidative phosphorylation.
A fibrous band of tissue that connects normally separate body regions.
A rare syndrome characterized by an abnormally dilated pupil, hypoflexia, and diaphoresis. The syndrome is usually caused by a viral or bacterial infection. The abnormally dilated pupil is caused by damage to postganglionic parasympathetic fibers innervating the eye.
Adiposis dolorosa, also known as Dercum disease, is characterized by generalized obesity and pronounced, disabling, and chronic pain in the adipose tissue of the proximal extremities, trunk, pelvic area, and buttocks; the face and hands are usually spared. There are a number of associated symptoms, including multiple lipomas, generalized weakness, fatigue, sleep disturbances, constipation, and psychiatric abnormalities. It is 5 to 30 times more common in women than men, and usually presents between 35 and 50 years of age (summary by Campen et al., 2001; review by Hansson et al., 2012). Based on a review of the literature and studies of 111 patients, Hansson et al. (2012) proposed a classification of Dercum disease into 4 types: (I) generalized diffuse form without clear lipomas, (II) generalized nodular form with multiple lipomas, (III) localized nodular form, and (IV) juxtaarticular form with solitary fatty deposits near joints.
A category of psychiatric disorders which are characterized by emotional or behavioral symptoms that develop within 3 months of a stressor and do not persist for more than an additional 6 months after the stressor is no longer present.
Temporary maladaptive depressive signs and symptoms associated with a life event.
Adjuvants are mostly pharmacological agents of drug or biological origin used to modify the antigenicity of immunization components, i.e., to stimulate, potentiate, or depress the immune response or to inhibit or enhance specific subclasses of immunocytes. Adjuvants augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. Classical agents (Freund's adjuvant, BCG, Corynebacterium parvum) contain bacterial antigens. Some adjuvants are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a variety of antigens, or antigen-specific, affecting a restricted type of immune response to a narrow group of antigens. Since adjuvants enhance the body's immune response, they can be considered a type of immune modulator.
Diseases of the uterine appendages (ADNEXA UTERI) including diseases involving the OVARY, the FALLOPIAN TUBES, and ligaments of the uterus (BROAD LIGAMENT; ROUND LIGAMENT).
Inflammation of the appendages of the uterus.
Pathological processes of the ADRENAL CORTEX.
Hormones synthesized in the cortex of the adrenal gland and consist of two subclasses, glucocorticoids (carbohydrate regulation) and mineralocorticoids (electrolyte regulation).
A benign or malignant (primary or metastatic) neoplasm affecting the adrenal cortex. (NCI05)
Abnormality of the adrenal glands, i.e., of the endocrine glands located at the top of the kindneys.
Abnormally high level of cortisol in the blood.
Conditions in which the production of adrenal CORTICOSTEROIDS falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the ADRENAL GLANDS, the PITUITARY GLAND, or the HYPOTHALAMUS.
A benign or malignant (primary or metastatic) neoplasm affecting the adrenal glands.
A genetic disorder characterized by defects in the synthesis of cortisol and/or aldosterone, resulting in hyperplasia of the adrenal cortical cells.
A benign, testicular or ovarian tumor, derived from adrenal embryonic rest cells. It is composed of hyperplastic adrenal cortical tissue, and it is associated with congenital adrenal hyperplasia.
The hydrochloride salt of the naturally occurring sympathomimetic amine with vasoconstricting, intraocular pressure-reducing, and bronchodilating activities. By stimulating vascular alpha-adrenergic receptors, epinephrine causes vasoconstriction, thereby increasing vascular resistance and blood pressure. When administered in the conjunctiva, this agent binds to alpha-adrenergic receptors in the iris sphincter muscle, resulting in vasoconstriction, a decrease in the production of aqueous humor, and a lowering of intraocular pressure. Through its beta1 receptor-stimulating actions, epinephrine increases the force and rate of myocardial contraction and relaxes bronchial smooth muscle, resulting in bronchodilation.
Refer to a class of agents that acts upon adrenergic receptors associated with activities of Sympathetic Nerve System. The adrenergic receptors (adrenoceptors) belongs to the family of seven membrane spanning domain receptors that require G protein signaling pathway. (NCI04)
Drugs that selectively bind to and activate alpha adrenergic receptors.
Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.
Drugs that selectively bind to and activate beta-adrenergic receptors.
Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.
Any agent that binds to and activates any of the adrenergic receptors.
An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).
Disorders in which the essential feature is a severe disturbance in mood (depression, anxiety, elation, and excitement) accompanied by psychotic symptoms such as delusions, hallucinations, gross impairment in reality testing, etc.
Mood or emotional responses dissonant with or inappropriate to the behavior and/or stimulus.
A complication of gastrojejunostomy (BILLROTH II PROCEDURE), a reconstructive GASTROENTEROSTOMY. It is caused by acute (complete) or chronic (intermittent) obstruction of the afferent jejunal loop due to HERNIA, intussusception, kinking, VOLVULUS, etc. It is characterized by PAIN and VOMITING of BILE-stained fluid.
A blood coagulation disorder characterized by the complete absence of fibrinogen in the blood, resulting in bleeding.
An insect-borne reovirus infection of horses, mules and donkeys in Africa and the Middle East; characterized by pulmonary edema, cardiac involvement, and edema of the head and neck.
A sometimes fatal ASFIVIRUS infection of pigs, characterized by fever, cough, diarrhea, hemorrhagic lymph nodes, and edema of the gallbladder. It is transmitted between domestic swine by direct contact, ingestion of infected meat, or fomites, or mechanically by biting flies or soft ticks (genus Ornithodoros).
Absence of the gamma fraction of serum globulin
A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis.
The clumping together of suspended material resulting from the action of AGGLUTININS.
Primary myelofibrosis is a condition characterized by the buildup of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. Because of the fibrosis, the bone marrow is unable to make enough normal blood cells. The shortage of blood cells causes many of the signs and symptoms of primary myelofibrosis.Initially, most people with primary myelofibrosis have no signs or symptoms. Eventually, fibrosis can lead to a reduction in the number of red blood cells, white blood cells, and platelets. A shortage of red blood cells (anemia) often causes extreme tiredness (fatigue) or shortness of breath. A loss of white blood cells can lead to an increased number of infections, and a reduction of platelets can cause easy bleeding or bruising.Because blood cell formation (hematopoiesis) in the bone marrow is disrupted, other organs such as the spleen or liver may begin to produce blood cells. This process, called extramedullary hematopoiesis, often leads to an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly). People with splenomegaly may feel pain or fullness in the abdomen, especially below the ribs on the left side. Other common signs and symptoms of primary myelofibrosis include fever, night sweats, and bone pain.Primary myelofibrosis is most commonly diagnosed in people aged 50 to 80 but can occur at any age.
A rare disorder characterized by the lack of ability to recognize individuals, objects, shapes, sounds, or smells. There is no loss of memory. It is caused by neurological damage in the brain, specifically in the occipital or parietal lobes.
A type of anxiety disorder characterized by avoidance of public places, especially where crowds gather.
An anxiety disorder characterized by agoraphobia in the absence of a history of panic attacks; the individual fears incapacitation or humiliation in open, public places or situations due to panic-like symptoms rather than a full-blown panic attack.
A decrease in the number of GRANULOCYTES; (BASOPHILS; EOSINOPHILS; and NEUTROPHILS).
Loss or impairment of the ability to write (letters, syllables, words, or phrases) due to an injury to a specific cerebral area or occasionally due to emotional factors. This condition rarely occurs in isolation, and often accompanies APHASIA. (From Adams et al., Principles of Neurology, 6th ed, p485; APA, Thesaurus of Psychological Index Terms, 1994)
Diseases in persons engaged in cultivating and tilling soil, growing plants, harvesting crops, raising livestock, or otherwise engaged in husbandry and farming. The diseases are not restricted to farmers in the sense of those who perform conventional farm chores: the heading applies also to those engaged in the individual activities named above, as in those only gathering harvest or in those only dusting crops.
A neurologic condition associated with the ACQUIRED IMMUNODEFICIENCY SYNDROME and characterized by impaired concentration and memory, slowness of hand movements, ATAXIA, incontinence, apathy, and gait difficulties associated with HIV-1 viral infection of the central nervous system. Pathologic examination of the brain reveals white matter rarefaction, perivascular infiltrates of lymphocytes, foamy macrophages, and multinucleated giant cells. (From Adams et al., Principles of Neurology, 6th ed, pp760-1; N Engl J Med, 1995 Apr 6;332(14):934-40)
A prodromal phase of infection with the human immunodeficiency virus (HIV). Laboratory criteria separating AIDS-related complex (ARC) from AIDS include elevated or hyperactive B-cell humoral immune responses, compared to depressed or normal antibody reactivity in AIDS; follicular or mixed hyperplasia in ARC lymph nodes, leading to lymphocyte degeneration and depletion more typical of AIDS; evolving succession of histopathological lesions such as localization of Kaposi's sarcoma, signaling the transition to the full-blown AIDS.
Development of a fibrotic constriction ring involving the base of one or more toes, conditioning eversion and absorption of distal structures, possibly progressing to spontaneous amputation.
A sensation of discomfort associated with air travel that may include nausea, vomiting, dizziness, or sweating.
Any hindrance to the passage of air into and out of the lungs.
An alkaloid found in the root of RAUWOLFIA SERPENTINA, among other plant sources. It is a class Ia antiarrhythmic agent that apparently acts by changing the shape and threshold of cardiac action potentials.
A syndrome characterized by a silent and inert state without voluntary motor activity despite preserved sensorimotor pathways and vigilance. Bilateral FRONTAL LOBE dysfunction involving the anterior cingulate gyrus and related brain injuries are associated with this condition. This may result in impaired abilities to communicate and initiate motor activities. (From Adams et al., Principles of Neurology, 6th ed, p348; Fortschr Neurol Psychiatr 1995 Feb;63(2):59-67)
A orthopoxvirus that causes a milder clinical syndrome than smallpox.
A benzimidazole broad-spectrum anthelmintic structurally related to MEBENDAZOLE that is effective against many diseases. (From Martindale, The Extra Pharmacopoeia, 30th ed, p38)
A congenital disorder characterized by partial or complete absence of melanin pigment in the eyes, hair and skin.
Increased concentration of albumin in the urine.
A racemic mixture of the r-isomer levalbuterol and s-albuterol, a short-acting sympathomimetic agent with bronchodilator activity. Albuterol stimulates beta-2 adrenergic receptors in the lungs, thereby activating the enzyme adenylate cyclase that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP concentrations relax bronchial smooth muscle, relieve bronchospasms, and reduce inflammatory cell mediator release, especially from mast cells. Albuterol although to a lesser extent, also stimulates beta-1 adrenergic receptors, thereby increasing the force and rate of myocardial contraction.
A mental disorder associated with chronic ethanol abuse (ALCOHOLISM) and nutritional deficiencies characterized by short term memory loss, confabulations, and disturbances of attention. (Adams et al., Principles of Neurology, 6th ed, p1139)
Substances interfering with the metabolism of ethyl alcohol, causing unpleasant side effects thought to discourage the drinking of alcoholic beverages. Alcohol deterrents are used in the treatment of alcoholism.
An acute organic mental disorder induced by cessation or reduction in chronic alcohol consumption. Clinical characteristics include CONFUSION; DELUSIONS; vivid HALLUCINATIONS; TREMOR; agitation; insomnia; and signs of autonomic hyperactivity (e.g., elevated blood pressure and heart rate, dilated pupils, and diaphoresis). This condition may occasionally be fatal. It was formerly called delirium tremens. (From Adams et al., Principles of Neurology, 6th ed, p1175)
A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.
A colorless liquid made by oxidation of aliphatic hydrocarbons that is used as a solvent and chemical intermediate.
An acute brain syndrome which results from the excessive ingestion of ETHANOL or ALCOHOLIC BEVERAGES.
Alcohol use disorder is a diagnosis made when an individual has severe problems related to drinking alcohol. Alcohol use disorder can cause major health, social, and economic problems, and can endanger affected individuals and others through behaviors prompted by impaired decision-making and lowered inhibitions, such as aggression, unprotected sex, or driving while intoxicated.Alcohol use disorder is a broad diagnosis that encompasses several commonly used terms describing problems with drinking. It includes alcoholism, also called alcohol addiction, which is a long-lasting (chronic) condition characterized by a powerful, compulsive urge to drink alcohol and the inability to stop drinking after starting. In addition to alcoholism, alcohol use disorder includes alcohol abuse, which involves problem drinking without addiction.Habitual excessive use of alcohol changes the chemistry of the brain and leads to tolerance, which means that over time the amount of alcohol ingested needs to be increased to achieve the same effect. Long-term excessive use of alcohol may also produce dependence, which means that when people stop drinking, they have physical and psychological symptoms of withdrawal, such as sleep problems, irritability, jumpiness, shakiness, restlessness, headache, nausea, sweating, anxiety, and depression. In severe cases, agitation, fever, seizures, and hallucinations can occur; this pattern of severe withdrawal symptoms is called delirium tremens.The heavy drinking that often occurs in alcohol use disorder, and can also occur in short-term episodes called binge drinking, can lead to a life-threatening overdose known as alcohol poisoning. Alcohol poisoning occurs when a large quantity of alcohol consumed over a short time causes problems with breathing, heart rate, body temperature, and the gag reflex. Signs and symptoms can include vomiting, choking, confusion, slow or irregular breathing, pale or blue-tinged skin, seizures, a low body temperature, a toxic buildup of substances called ketones in the blood (alcoholic ketoacidosis), and passing out (unconsciousness). Coma, brain damage, and death can occur if alcohol poisoning is not treated immediately.Chronic heavy alcohol use can also cause long-term problems affecting many organs and systems of the body. These health problems include irreversible liver disease (cirrhosis), inflammation of the pancreas (pancreatitis), brain dysfunction (encephalopathy), nerve damage (neuropathy), high blood pressure (hypertension), stroke, weakening of the heart muscle (cardiomyopathy), irregular heartbeats (arrhythmia), and immune system problems. Long-term overuse of alcohol also increases the risk of certain cancers, including cancers of the mouth, throat, esophagus, liver, and breast. Alcohol use in pregnant women can cause birth defects and fetal alcohol syndrome, which can lead to lifelong physical and behavioral problems in the affected child.
A class of compounds where a hydroxyl (OH) group is attached to single bonded hydrocarbons. Alcohols are classified according to the position of the carbon atom with the attached hydroxyl group (i.e. primary alcohols are alcohols with the OH group attached to the primary carbon atom, C1). Uses include solvents, astringents, and anti-infective activity.
A non-depolarizing skeletal muscle relaxant similar to TUBOCURARINE. It is used as an anesthesia adjuvant.
A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium.
agent that counteracts or opposes the action of aldosterone.
A slow progressive disease of mink caused by the ALEUTIAN MINK DISEASE VIRUS. It is characterized by poor reproduction, weight loss, autoimmunity, hypergammaglobulinemia, increased susceptibility to bacterial infections, and death from renal failure. The disease occurs in all color types, but mink which are homozygous recessive for the Aleutian gene for light coat color are particularly susceptible.
An acquired type of sensory aphasia where damage to the brain leads to the loss of the ability to read.
A deficit in emotional awareness characterized by difficulties in recognizing and expressing feelings and emotions manifested as a limited ability to respond to facial clues or other signs of emotions in others often accompanied by detached connections to others.
A short-acting opioid anesthetic and analgesic derivative of FENTANYL. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients.
A progesterone that has been used in ESTRUS SYNCHRONIZATION and has been evaluated as an injectable contraceptive in combination with estradiol enanthate. It is also used therapeutically as a topical anti-inflammatory and is applied topically in the treatment of ACNE.
A family or group of nitrogen-containing base compounds primarily derived from plant and animal sources. Many alkaloids are used medicinally, including cancer therapy.
A pathological condition that removes acid or adds base to the body fluids.
A condition in which the blood pH is greater than normal, secondary to impaired gas exchange.
Alkaptonuria is caused by deficiency of homogentisate 1,2-dioxygenase, an enzyme that converts homogentisic acid (HGA) to maleylacetoacetic acid in the tyrosine degradation pathway. The three major features of alkaptonuria are the presence of HGA in the urine, ochronosis (bluish-black pigmentation in connective tissue), and arthritis of the spine and larger joints. Oxidation of the HGA excreted in the urine produces a melanin-like product and causes the urine to turn dark on standing. Ochronosis occurs only after age 30 years; arthritis often begins in the third decade. Other manifestations include pigment deposition, aortic or mitral valve calcification or regurgitation and occasionally aortic dilatation, renal stones, and prostate stones.
Agents that replace hydrogen atom(s) in biologically active molecules with alky radical(s), hindering proper function. Alkylating agents exhibit cytotoxic effects through the alkylation of DNA, resulting in strand cross-linking, ultimately inhibiting DNA replication and cell growth.
A urea hydantoin that is found in URINE and PLANTS and is used in dermatological preparations.
Allergic rhinitis with a positive skin prick test (SPT equal or greater than 3 mm) to any allergen.
A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.
The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.
Possesses an unusual and selective cytotoxicity for VASCULAR SMOOTH MUSCLE cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation.
A synthetic steroid with progestational activity.
An inhibitor of glutamate decarboxylase and an antagonist of GAMMA-AMINOBUTYRIC ACID. It is used to induce convulsions in experimental animals.
A respiratory stimulant that enhances respiration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. The drug increases arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease. It may also prove useful in the treatment of nocturnal oxygen desaturation without impairing the quality of sleep.
Absence of hair from areas where it is normally present.
Alopecia areata is a common disorder that causes hair loss. ""Alopecia"" is a Latin term that means baldness, and ""areata"" refers to the patchy nature of the hair loss that is typically seen with this condition.In most people with alopecia areata, hair falls out in small, round patches, leaving coin-sized areas of bare skin. This patchy hair loss occurs most often on the scalp but can affect other parts of the body as well. Uncommonly, the hair loss involves the entire scalp (in which case the condition is known as alopecia totalis) or the whole body (alopecia universalis). Other rare forms of alopecia areata, which have different patterns of hair loss, have also been reported.Alopecia areata affects people of all ages, although it most commonly appears in adolescence or early adulthood. Hair loss occurs over a period of weeks. The hair usually grows back after several months, although it may fall out again. In some cases, unpredictable cycles of hair loss followed by regrowth can last for years. In addition to hair loss, some affected individuals have fingernail and toenail abnormalities, such as pits on the surface of the nails.The hair loss associated with alopecia areata is not painful or disabling. However, it causes changes in a person's appearance that can profoundly affect quality of life and self-esteem. In some people, the condition can lead to depression, anxiety, and other emotional or psychological issues.
A disease of the pilosebaceous unit, presenting clinically as grouped follicular papules or plaques with associated hair loss. It is caused by mucinous infiltration of tissues, and usually involving the scalp, face, and neck. It may be primary (idiopathic) or secondary to mycosis fungoides or reticulosis.
Alpha-1-antitrypsin (418 aa, ~47 kDa) is encoded by the human SERPINA1 gene. This protein plays a role in regulation of proteolysis.
One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.
A family of hydrolases that cleaves alpha-linkages in polysaccharides, such as starch and glycogen, and yield glucose and maltose. This family includes the amylase forms that are produced by mammals. In humans, alpha-amylase is produced by salivary glands and the pancreas.
A chlorinated PROPANEDIOL with antifertility activity in males used as a chemosterilant in rodents.
A difluoromethylated ornithine compound with antineoplastic activity. Eflornithine irreversibly inhibits ornithine decarboxylase, an enzyme required for polyamine biosynthesis, thereby inhibiting the formation and proliferation of tumor cells. Polyamines are involved in nucleosome oligomerization and DNA conformation, creating a chromatin environment that stimulates neoplastic transformation of cells. This agent has been shown to induce apoptosis in leiomyoma cells. (NCI04)
An enzyme that catalyzes the hydrolysis of terminal, non-reducing alpha-D-galactose residues in alpha-galactosides including galactose oligosaccharides, galactomannans, and galactolipids.
Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.
Alpha-thalassemia (a-thalassemia) has two clinically significant forms: hemoglobin Bart hydrops fetalis (Hb Bart) syndrome, caused by deletion of all four a-globin genes; and hemoglobin H (HbH) disease, most frequently caused by deletion of three a-globin genes. Hb Bart syndrome, the more severe form, is characterized by fetal onset of generalized edema, pleural and pericardial effusions, and severe hypochromic anemia, in the absence of ABO or Rh blood group incompatibility. Additional clinical features include marked hepatosplenomegaly, extramedullary erythropoiesis, hydrocephalus, and cardiac and urogenital defects. Death usually occurs in the neonatal period. HbH disease is characterized by microcytic hypochromic hemolytic anemia, splenomegaly, mild jaundice, and sometimes thalassemia-like bone changes. Individuals with HbH disease may develop gallstones and experience acute episodes of hemolysis in response to oxidant drugs and infections.
An opioid analgesic chemically related to and with an action resembling that of MEPERIDINE, but more rapid in onset and of shorter duration. It has been used in obstetrics, as pre-operative medication, for minor surgical procedures, and for dental procedures. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1067)
A synthetic progestational dihydroxy derivative of PROGESTERONE. Its acetonide possesses anti-inflammatory properties.
A triazolobenzodiazepine agent with anxiolytic, sedative-hypnotic and anticonvulsant activities. Alprazolam binds to a specific site distinct from the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) binding site on the benzodiazepine-GABA-A-chloride ionophore receptor complex located in the limbic, thalamic and hypothalamic regions of the central nervous system (CNS). This binding causes an allosteric modification of the receptor and enhances the affinity of GABA to the receptor leading to an increase in the frequency of chloride-channel opening events. This leads to an increase in chloride ion conductance, neuronal hyperpolarization, inhibition of the action potential and leads to a decrease in neuronal excitability.
One of the ADRENERGIC BETA-ANTAGONISTS used as an antihypertensive, anti-anginal, and anti-arrhythmic agent.
A potent vasodilator agent that increases peripheral blood flow.
Multiple symptoms associated with reduced oxygen at high ALTITUDE.
Aluminum metal sulfate compounds used medically as astringents and for many industrial purposes. They are used in veterinary medicine for the treatment of ulcerative stomatitis, leukorrhea, conjunctivitis, pharyngitis, metritis, and minor wounds.
A metallic element in the boron group with atomic symbol Al, atomic number 13, and atomic weight 27.
A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an adjuvant in bacterins and vaccines, in water purification, etc.
Resorption or wasting of the tooth-supporting bone (ALVEOLAR PROCESS) in the MAXILLA or MANDIBLE.
A common interstitial lung disease caused by hypersensitivity reactions of PULMONARY ALVEOLI after inhalation of and sensitization to environmental antigens of microbial, animal, or chemical sources. The disease is characterized by lymphocytic alveolitis and granulomatous pneumonitis.
Alzheimer disease is the most common form of progressive dementia in the elderly. It is a neurodegenerative disorder characterized by the neuropathologic findings of intracellular neurofibrillary tangles (NFT) and extracellular amyloid plaques that accumulate in vulnerable brain regions (Sennvik et al., 2000). Terry and Davies (1980) pointed out that the 'presenile' form, with onset before age 65, is identical to the most common form of late-onset or 'senile' dementia, and suggested the term 'senile dementia of the Alzheimer type' (SDAT). Haines (1991) reviewed the genetics of AD. Selkoe (1996) reviewed the pathophysiology, chromosomal loci, and pathogenetic mechanisms of Alzheimer disease. Theuns and Van Broeckhoven (2000) reviewed the transcriptional regulation of the genes involved in Alzheimer disease. Genetic Heterogeneity of Alzheimer Disease Alzheimer disease is a genetically heterogeneous disorder. See also AD2 (104310), associated with the APOE*4 allele (107741) on chromosome 19; AD3 (607822), caused by mutation in the presenilin-1 gene (PSEN1; 104311) on 14q; and AD4 (606889), caused by mutation in the PSEN2 gene (600759) on 1q31. There is evidence for additional AD loci on other chromosomes; see AD5 (602096) on 12p11, AD6 (605526) on 10q24, AD7 (606187) on 10p13, AD8 (607116) on 20p, AD9 (608907), associated with variation in the ABCA7 gene (605414) on 19p13, AD10 (609636) on 7q36, AD11 (609790) on 9q22, AD12 (611073) on 8p12-q22, AD13 (611152) on 1q21, AD14 (611154) on 1q25, AD15 (611155) on 3q22-q24, AD16 (300756) on Xq21.3, AD17 (615080) on 6p21.2, and AD18 (615590), associated with variation in the ADAM10 gene (602192) on 15q21. Evidence also suggests that mitochondrial DNA polymorphisms may be risk factors in Alzheimer disease (502500). Finally, there have been associations between AD and various polymorphisms in other genes, including alpha-2-macroglobulin (A2M; 103950.0005), low density lipoprotein-related protein-1 (LRP1; 107770), the transferrin gene (TF; 190000), the hemochromatosis gene (HFE; 613609), the NOS3 gene (163729), the vascular endothelial growth factor gene (VEGF; 192240), the ABCA2 gene (600047), and the TNF gene (191160) (see MOLECULAR GENETICS).
A synthetic tricyclic amine with antiviral, antiparkinsonian, and antihyperalgesic activities. Amantadine appears to exert its antiviral effect against the influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the release of infectious viral nucleic acids into host cells. Furthermore, this agent prevents virus assembly during virus replication. Amantadine exerts its antiparkinsonian effects by stimulating the release of dopamine from striatal dopaminergic nerve terminals and inhibiting its pre-synaptic reuptake. This agent may also exert some anticholinergic effect through inhibition of N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine, resulting in antihyperalgesia.
The sulfate salt of amantadine, a synthetic tricyclic amine with antiviral, antiparkinsonian, and antihyperalgesic activities. Amantadine appears to exert its antiviral effect against the influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the release of infectious viral nucleic acids into host cells; furthermore, this agent prevents virus assembly during virus replication. Amantadine exerts its antiparkinsonian effects by stimulating the release of dopamine from striatal dopaminergic nerve terminals and inhibiting its pre-synaptic reuptake. This agent may also exert some anticholinergic effect through inhibition of N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine, resulting in antihyperalgesia.
A bisquaternary ammonium alcohol with parasympathomimetic activity. The positive charge of ambenonium allows it to act as an acetylcholinesterase inhibitor by binding to the anionic site at the reactive center of acetylcholinesterase, preventing the breakdown of acetylcholine and producing an indirect cholinomimetic effect at both nicotinic and muscarinic receptors. Ambenonium also has direct agonist activity at nicotinic receptors, potentiating the cholinomimetic effect at the neuromuscular junction.
A quaternary ammonium compound that is an inhibitor of cholinesterase activity with actions similar to those of NEOSTIGMINE, but of longer duration. Ambenonium is given by mouth in the treatment of myasthenia gravis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1112)
A nonspecific term referring to impaired vision. Major subcategories include stimulus deprivation-induced amblyopia and toxic amblyopia. Stimulus deprivation-induced amblyopia is a developmental disorder of the visual cortex. A discrepancy between visual information received by the visual cortex from each eye results in abnormal cortical development. STRABISMUS and REFRACTIVE ERRORS may cause this condition. Toxic amblyopia is a disorder of the OPTIC NERVE which is associated with ALCOHOLISM, tobacco SMOKING, and other toxins and as an adverse effect of the use of some medications.
A metabolite of BROMHEXINE that stimulates mucociliary action and clears the air passages in the respiratory tract. It is usually administered as the hydrochloride.
A parasitic infectious disorder caused by amoebas. The parasite may cause colitis which is manifested with bloody diarrhea, abdominal pain, nausea and fever. In rare cases it may spread to the liver, brain and lungs.
Agents which are destructive to amebae, especially the parasitic species causing AMEBIASIS in man and animal.
A congenital malformation characterized by the complete absence of all limbs.
The most common odontogenic tumor, arising from the epithelial component of the embryonic tooth and usually affecting the molar-ramus region of the mandible or maxilla. Although most ameloblastomas are morphologically and clinically benign, they may cause extensive local destruction, recur, or metastasize.
A clinically and genetically heterogeneous group of hereditary conditions characterized by malformed DENTAL ENAMEL, usually involving DENTAL ENAMEL HYPOPLASIA and/or TOOTH HYPOMINERALIZATION.
Absence of menses for an interval of time equivalent to a total of more than (or equal to) 3 previous cycles or 6 months. [pmid:22594864]
A completely man-made radioactive actinide with atomic symbol Am, and atomic number 95. Its valence can range from +3 to +6. Because of its nonmagnetic ground state, it is an excellent superconductor. It is also used in bone mineral analysis and as a radiation source for radiotherapy.
A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705)
A highly fluorescent anti-infective dye used clinically as a topical antiseptic and experimentally as a mutagen, due to its interaction with DNA. It is also used as an intracellular pH indicator.
A reaction that produces an ""activated"" amino acid derivative, such as amino acyl adenylate, or amino acylphosphorylate and provides energy for the amino acid to be incorporated into a peptide, protein, or other macromolecule.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
An inherited disorder that affects the metabolism of the amino acids. Representative examples include alkaptonuria, homocystinuria, tyrosinemia, and phenylketonuria.
Any organic compounds containing amino (-NH2) and carboxyl (-COOH) groups. In biochemistry, used to refer to the twenty-plus L-alpha-amino acids found in proteins.
Amino acids that are not synthesized by the human body in amounts sufficient to carry out physiological functions. They are obtained from dietary foodstuffs.
Compounds possessing both a hydroxyl (-OH) and an amino group (-NH2).
A group of inherited kidney disorders characterized by the abnormally elevated levels of AMINO ACIDS in URINE. Genetic mutations of transport proteins result in the defective reabsorption of free amino acids at the PROXIMAL RENAL TUBULES. Renal aminoaciduria are classified by the specific amino acid or acids involved.
Acridines which are substituted in any position by one or more amino groups or substituted amino groups.
A synthetic derivative of the sedative and anticonvulsant glutethimide with anti-steroid properties. Originally used as an anticonvulsant, aminoglutethimide also blocks adrenal steroidogenesis by inhibiting the enzymatic conversion of cholesterol to pregnenolone. In addition, this agent blocks the peripheral aromatization of androgenic precursors to estrogens. Aminoglutethimide does not suppress ovarian estrogen production.
Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.
An imidazole derivative which is a metabolite of the antineoplastic agents BIC and DIC. By itself, or as the ribonucleotide, it is used as a condensation agent in the preparation of nucleosides and nucleotides. Compounded with orotic acid, it is used to treat liver diseases.
A compound produced from succinyl-CoA and GLYCINE as an intermediate in heme synthesis. It is used as a PHOTOCHEMOTHERAPY for actinic KERATOSIS.
A compound that inhibits aminobutyrate aminotransferase activity in vivo, thereby raising the level of gamma-aminobutyric acid in tissues.
A drug combination that contains THEOPHYLLINE and ethylenediamine. It is more soluble in water than theophylline but has similar pharmacologic actions. It's most common use is in bronchial asthma, but it has been investigated for several other applications.
A pyrazolone with analgesic, anti-inflammatory, and antipyretic properties but has risk of AGRANULOCYTOSIS. A breath test with 13C-labeled aminopyrine has been used as a non-invasive measure of CYTOCHROME P-450 metabolic activity in LIVER FUNCTION TESTS.
An amphetamine-like anorectic agent. It may cause pulmonary hypertension.
A group of 2-hydroxybenzoic acids that can be substituted by amino groups at any of the 3-, 4-, 5-, or 6-positions.
An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.
A derivative of dibenzocycloheptadiene and a tricyclic antidepressant. Amitriptyline inhibits the re-uptake of norepinephrine and serotonin by the presynaptic neuronal membrane in the central nervous system (CNS), thereby increasing the synaptic concentration of norepinephrine and serotonin. Due to constant stimulation to these receptors, amitriptyline may produce a downregulation of adrenergic and serotonin receptors, which may contribute to the antidepressant activity.
A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.
A systemic and urinary acidifying salt. Ammonium chloride helps maintain pH and exerts a mild diuretic effect. This acid forming salt also exerts an expectorant effect by irritating the mucous membranes and is used for alleviation of cough.
Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)
Loss of the ability to recall information that had been previously encoded in memory prior to a specified or approximate point in time. This process may be organic or psychogenic in origin. Organic forms may be associated with CRANIOCEREBRAL TRAUMA; CEREBROVASCULAR ACCIDENTS; SEIZURES; DEMENTIA; and a wide variety of other conditions that impair cerebral function. (From Adams et al., Principles of Neurology, 6th ed, pp426-9)
A rare congenital disorder which is caused by entrapment of anatomic parts of the fetus in fibrous amniotic bands during pregnancy. It may result in the formation of constriction rings around the digits and upper and lower extremities, swelling of the extremities and congenital amputations.
A barbiturate with hypnotic and sedative properties (but not antianxiety). Adverse effects are mainly a consequence of dose-related CNS depression and the risk of dependence with continued use is high. (From Martindale, The Extra Pharmacopoeia, 30th ed, p565)
A 4-aminoquinoline compound with anti-inflammatory properties.
A tricyclic antidepressant of the dibenzoxazepine class. Amoxapine exerts its antidepressant effect by inhibiting the re-uptake of norepinephrine and, to a lesser degree, of serotonin, at adrenergic nerve endings and blocks the response of dopamine receptors to dopamine. This drug is used to treat symptoms of depression and may cause tardive dyskinesia. Amoxapine also binds to alpha-adrenergic, histaminergic, and cholinergic receptors which accounts for many of the side effects seen with this agent.
Chemical racemic free base or equal parts of enantiomers levoamphetamine and dextroamphetamine in their pure amine or salt forms.
Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.
A veterinary coccidiostat that interferes with THIAMINE metabolism.
A metabolite of AMINOPYRINE with analgesic and anti-inflammatory properties. It is used as a reagent for biochemical reactions producing peroxides or phenols. Ampyrone stimulates LIVER MICROSOMES and is also used to measure extracellular water.
A positive inotropic cardiotonic (CARDIOTONIC AGENTS) with vasodilator properties, phosphodiesterase 3 inhibitory activity, and the ability to stimulate calcium ion influx into the cardiac cell.
An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.
A cyanogenic glucoside isolated from almonds and seeds of other plants of the family Rosaceae. Amygdalin is converted by plant emulsin (a combination of a glucosidase and a nitrilase) or hydrochloric acid into benzaldehyde, D-glucose, and hydrocyanic acid. (NCI04)
A vasodilator that is administered by inhalation. It is also used recreationally due to its supposed ability to induce euphoria and act as an aphrodisiac.
A group of amylolytic enzymes that cleave starch, glycogen, and related alpha-1,4-glucans. (Stedman, 25th ed) EC 3.2.1.-.
A disorder characterized by the localized or diffuse accumulation of amyloid protein in various anatomic sites. It may be primary, due to clonal plasma cell proliferations; secondary, due to long standing infections, chronic inflammatory disorders, or malignancies; or familial. It may affect the nerves, skin, tongue, joints, heart, liver, spleen, kidneys and adrenal glands.
congenital atonic pseudoparalysis observed especially in infants and characterized by absence of muscular tone only in muscles innervated by the spinal nerves; also known as Oppenheim's disease or syndrome or congenital atonic pseudoparalysis.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper motor neurons (UMN) and lower motor neurons (LMN). UMN signs include hyperreflexia, extensor plantar response, increased muscle tone, and weakness in a topographic representation. LMN signs include weakness, muscle wasting, hyporeflexia, muscle cramps, and fasciculations. Initial presentation varies. Affected individuals typically present with either asymmetric focal weakness of the extremities (stumbling or poor handgrip) or bulbar findings (dysarthria, dysphagia). Other findings may include muscle fasciculations, muscle cramps, and labile affect, but not necessarily mood. Regardless of initial symptoms, atrophy and weakness eventually affect other muscles. The mean age of onset is 56 years in individuals with no known family history and 46 years in individuals with more than one affected family member (familial ALS or FALS). Average disease duration is about three years, but it can vary significantly. Death usually results from compromise of the respiratory muscles.
A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.
A syndrome characterized by indifference to PAIN despite the ability to distinguish noxious from non-noxious stimuli. Absent corneal reflexes and INTELLECTUAL DISABILITY may be associated. Familial forms with autosomal recessive and autosomal dominant patterns of inheritance have been described. (Adams et al., Principles of Neurology, 6th ed, p1343)
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.
An acute hypersensitivity reaction due to exposure to a previously encountered antigen.
A morphologic finding indicating the presence of a malignant cellular infiltrate characterized by the presence of large pleomorphic cells, necrosis, and high mitotic activity in a tissue sample.
Infections with bacteria of the family ANAPLASMATACEAE.
A disease usually in cattle caused by parasitization of the red blood cells by bacteria of the genus ANAPLASMA.
A proteolytic enzyme and defibrinogenating agent derived from the venom of the Malayan pit viper, with profibrinolytic and anticoagulant activities. Upon administration, ancrod cleaves fibrinogen and releases A-fibrinopeptides. This inactivates fibrinogen and leads to a reduction in blood viscosity, increases blood flow and perfusion of the microcirculation.
Infection by hookworms of the genus Ancylostoma.
Compounds which inhibit or antagonize the biosynthesis or actions of androgens.
A synthetic or animal-derived hormone that is chemically or functionally similar or identical to endogenous androgen with potential use in therapeutic applications.
Synthetic derivatives of the male hormone, androgen, that promote tissue growth by increasing the metabolic processes involved with protein synthesis and are used to promote weight gain in wasting diseases. They are used by bodybuilders and athletes to increase muscle mass, strength, and stamina.
A delta-4 C19 steroid that is produced not only in the TESTIS, but also in the OVARY and the ADRENAL CORTEX. Depending on the tissue type, androstenedione can serve as a precursor to TESTOSTERONE as well as ESTRONE and ESTRADIOL.
A reduction in erythrocytes volume or hemoglobin concentration. [HPO:probinson]
Anemia due to a disorder that is persistent or long-standing in nature.
Aplastic anemia is a serious disorder of the bone marrow that affects between 2 and 5 persons per million per year. About 75% of these cases are classified as idiopathic (Young, 2000). In about 15% of cases a drug or infection can be identified that precipitates the aplasia, although why only some individuals are susceptible is unclear. In about 5 to 10% of patients, the aplastic anemia is constitutional--i.e., is familial or presents with one or more associated somatic abnormalities (summary by Vulliamy et al., 2002).
The most severe form of beta thalassemia that is characterized by the lack of functional beta-globin chain production resulting in the absence of hemoglobin A.
Congenital dyserythropoietic anemia (CDA) is an inherited blood disorder that affects the development of red blood cells. This disorder is one of many types of anemia, which is a condition characterized by a shortage of red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues. The resulting symptoms can include tiredness (fatigue), weakness, pale skin, and other complications.Researchers have identified three major types of CDA: type I, type II, and type III. The types have different genetic causes and different but overlapping patterns of signs and symptoms.CDA type I is characterized by moderate to severe anemia. It is usually diagnosed in childhood or adolescence, although in some cases, the condition can be detected before birth. Many affected individuals have yellowing of the skin and eyes (jaundice) and an enlarged liver and spleen (hepatosplenomegaly). This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis). Rarely, people with CDA type I are born with skeletal abnormalities, most often involving the fingers and/or toes.The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.The signs and symptoms of CDA type III tend to be milder than those of the other types. Most affected individuals do not have hepatosplenomegaly, and iron does not build up in tissues and organs. In adulthood, abnormalities of a specialized tissue at the back of the eye (the retina) can cause vision impairment. Some people with CDA type III also have a blood disorder known as monoclonal gammopathy, which can lead to a cancer of white blood cells (multiple myeloma).Several other variants of CDA have been described, although they appear to be rare and not much is known about them. Once researchers discover the genetic causes of these variants, some of them may be grouped with the three major types of CDA.
A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).
Hemolytic anemia, the cause of which is not present at birth.
Acquired hemolytic anemia due to the presence of AUTOANTIBODIES which agglutinate or lyse the patient's own RED BLOOD CELLS.
A congenital hemolytic anemia caused by defects of the erythrocyte membrane, enzyme deficiencies, or hemoglobinopathies.
Any one of a group of congenital hemolytic anemias in which there is no abnormal hemoglobin or spherocytosis and in which there is a defect of glycolysis in the erythrocyte. Common causes include deficiencies in GLUCOSE-6-PHOSPHATE ISOMERASE; PYRUVATE KINASE; and GLUCOSE-6-PHOSPHATE DEHYDROGENASE.
A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes.
A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
A disorder characterized by the presence of ANEMIA, abnormally large red blood cells (megalocytes or macrocytes), and MEGALOBLASTS.
Anemia characterized by appearance of immature myeloid and nucleated erythrocytes in the peripheral blood, resulting from infiltration of the bone marrow by foreign or abnormal tissue.
The mildest form of erythroblastosis fetalis in which anemia is the chief manifestation.
A megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B 12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor. (Dorland, 27th ed)
A myelodysplastic syndrome characterized mainly by dysplasia of the erythroid series. Refractory anemia is uncommon. It is primarily a disease of older adults. The median survival exceeds 5 years. (WHO, 2001)
A myelodysplastic syndrome characterized by the presence of 5-19% myeloblasts in the bone marrow or 2-19% blasts in the peripheral blood. It includes two categories: myelodysplastic syndrome with excess blasts-1 and myelodysplastic syndrome with excess blasts-2.
Sickle cell disease (SCD) is characterized by intermittent vaso-occlusive events and chronic hemolytic anemia. Vaso-occlusive events result in tissue ischemia leading to acute and chronic pain as well as organ damage that can affect any organ system, including the bones, spleen, liver, brain, lungs, kidneys, and joints. Dactylitis (pain and/or swelling of the hands or feet) is often the earliest manifestation of SCD. In children, the spleen can become engorged with blood cells in a ""splenic sequestration."" The spleen is particularly vulnerable to infarction and the majority of individuals with SCD who are not on hydroxyurea or transfusion therapy become functionally asplenic in early childhood, increasing their risk for certain types of bacterial infections. Acute chest syndrome is a major cause of mortality in SCD. Chronic hemolysis can result in varying degrees of anemia, jaundice, cholelithiasis, and delayed growth and sexual maturation. Individuals with the highest rates of hemolysis are predisposed to pulmonary artery hypertension, priapism, and leg ulcers but may be relatively protected from vaso-occlusive pain.
A type of sideroblastic anemia that is not responsive to treatment.
Anemia resulting from an abnormality of glutathione deficiency.
Anencephaly is characterized by the absence of cranial vault and brain tissues in the fetus. It is considered an extreme form of neural tube defect (182940) (summary by Singh et al., 2017).
Agents that are administered in association with anesthetics to increase effectiveness, improve delivery, or decrease required dosage.
A pharmacological agent that acts in a reversible fashion and can be applied either locally or systemically to cause a partial or total loss of sensation and pain or to induce unconsciousness.
Intravenous anesthetics that induce a state of sedation, immobility, amnesia, and marked analgesia. Subjects may experience a strong feeling of dissociation from the environment. The condition produced is similar to NEUROLEPTANALGESIA, but is brought about by the administration of a single drug. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed)
Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.
A substituted dithiolthione and analog of chemopreventive agent oltipraz. Anethole trithione is a bile secretion-stimulating drug that restores salivation and relieves the discomfort of dry mouth in chemotherapy-induced xerostomia. In addition, this agent has exhibited chemopreventive properties. The mechanism of action for the chemopreventive and xerostomia properties have not been fully elucidated.
A chromosomal abnormality in which there is an addition or loss of chromosomes within a set (e.g., 23 + 22 or 23 + 24).
Abnormal outpouching or sac-like dilatation in the wall of an atery, vein or the heart.
A separation (dissection) of the layers of an artery.
Aneurysm due to growth of microorganisms in the arterial wall, or infection arising within preexisting arteriosclerotic aneurysms.
Paroxysmal chest pain that occurs with exertion or stress and is related to myocardial ischemia.
A clinical syndrome characterized by the development of CHEST PAIN at rest with concomitant transient ST segment elevation in the ELECTROCARDIOGRAM, but with preserved exercise capacity.
Angina pectoris (or equivalent type of ischemic discomfort) which has recently changed in frequency, duration, intensity, or occurs at rest.
Irregular lines in the deep retina that are typically configured in a radiating fashion and emanate from the optic disc. Angioid streaks are crack-like dehiscences in abnormally thickened and calcified Bruch's membrane, resulting in atrophy of the overlying retinal pigment epithelium. They may be associated with a number of endocrine, metabolic, and connective tissue abnormalities but are frequently idiopathic.
A vascular lesion defined histologically as one or more dilated blood vessels lying directly subepidermal and showing an epidermal proliferative reaction. Clinically, angiokeratoma presents as a small, raised, dark-red spot.
Fabry disease results from deficient activity of the enzyme alpha-galactosidase A (a-Gal A) and progressive lysosomal deposition of globotriaosylceramide (GL-3) in cells throughout the body. The classic form, occurring in males with less than 1% a-Gal A enzyme activity, usually has its onset in childhood or adolescence with periodic crises of severe pain in the extremities (acroparesthesia), the appearance of vascular cutaneous lesions (angiokeratomas), sweating abnormalities (anhidrosis, hypohidrosis, and rarely hyperhidrosis), characteristic corneal and lenticular opacities, and proteinuria. Gradual deterioration of renal function to end-stage renal disease (ESRD) usually occurs in men in the third to fifth decade. In middle age, most males successfully treated for ESRD develop cardiac and/or cerebrovascular disease, a major cause of morbidity and mortality. Heterozygous females typically have milder symptoms at a later age of onset than males. Rarely, they may be relatively asymptomatic throughout a normal life span or may have symptoms as severe as those observed in males with the classic phenotype. In contrast, males with greater than 1% a-Gal A activity may have: (1) a cardiac variant phenotype that usually presents in the sixth to eighth decade with left ventricular hypertrophy, cardiomyopathy and arrhythmia, and proteinuria, but without ESRD; or (2) a renal variant phenotype, associated with ESRD but without the skin lesions or pain; or (3) cerebrovascular disease presenting as stroke or transient ischemic attack.
A hemangioma arising from the skin. It is characterized by the presence of epithelioid endothelial cells.
A solitary, slowly growing, nodular mass, most often affecting the extremities. It is composed of fibrous and histiocytic cells which infiltrate the dermis and occasionally the underlying subcutaneous tissue. Usually local excision is curative. Recurrences are reported only in a small minority of cases.
A benign diffuse vascular proliferation usually occurring in young adults. It is characterized by the formation of capillary-sized and cavernous vascular spaces. Patients present with diffuse persistent swelling.
Rapid swelling (edema) of the dermis, subcutaneous tissue, mucosa and submucosal tissues of the skin of the face, normally around the mouth, and the mucosa of the mouth and/or throat, as well as the tongue during a period of minutes to several hours. The swelling can also occur elsewhere, typically in the hands. Angioedema is similar to urticaria, but the swelling is subcutaneous rather than on the epidermis.
The octapeptide amide of bovine angiotensin II used to increase blood pressure by vasoconstriction.
An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.
A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.
Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.
Dye and chemical solution stains for medical purposes are mixtures of synthetic or natural dyes or nondye chemicals in solutions used in staining cells and tissues for diagnostic histopathology, cytopathology, or hematology.
An alkylating mustard with antineoplastic activity. Aniline mustard forms covalent linkages with nucleophilic centers, resulting in depurination, base miscoding and strand scission, and crosslinking of DNA strands, all of which contribute to its cytotoxicity. (NCI04)
Diseases that occur in VERTEBRATE animals.
Aniridia is an eye disorder characterized by a complete or partial absence of the colored part of the eye (the iris). These iris abnormalities may cause the pupils to be abnormal or misshapen. Aniridia can cause reduction in the sharpness of vision (visual acuity) and increased sensitivity to light (photophobia).People with aniridia can also have other eye problems. Increased pressure in the eye (glaucoma) typically appears in late childhood or early adolescence. Clouding of the lens of the eye (cataracts), occur in 50 percent to 85 percent of people with aniridia. In about 10 percent of affected people, the structures that carry information from the eyes to the brain (optic nerves) are underdeveloped. Individuals with aniridia may also have involuntary eye movements (nystagmus) or underdevelopment of the region at the back of the eye responsible for sharp central vision (foveal hypoplasia). Many of these eye problems contribute to progressive vision loss in affected individuals. The severity of symptoms is typically the same in both eyes.Rarely, people with aniridia have behavioral problems, developmental delay, and problems detecting odors.
A condition in which the ocular image of an object as seen by one eye differs in size and shape from that seen by the other.
Anisocoria, or unequal pupil size, may represent a benign physiologic variant or a manifestation of disease.
A condition of an inequality of refractive power of the two eyes.
A reduction of joint mobility resulting from changes involving the articular surfaces.
A language dysfunction characterized by the inability to name people and objects that are correctly perceived. The individual is able to describe the object in question, but cannot provide the name. This condition is associated with lesions of the dominant hemisphere involving the language areas, in particular the TEMPORAL LOBE. (From Adams et al., Principles of Neurology, 6th ed, p484)
A rare congenital abnormality characterized by the complete absence of ocular tissue in the orbit.
A lack or loss of appetite for food (as a medical condition).
A disorder most often seen in adolescent females characterized by a refusal to maintain a minimally normal body weight, an intense fear of gaining weight, a disturbance in body image, and, in postmenarcheal females, the development of amenorrhea.
Absence of the sense of smell. (Dorland, 27th ed)
Suspension or cessation of OVULATION in animals or humans with follicle-containing ovaries (OVARIAN FOLLICLE). Depending on the etiology, OVULATION may be induced with appropriate therapy.
Absence or reduction of oxygen in body tissue.
Natural or synthetic compounds or mixtures, Antiacid Preparations such as sodium bicarbonate, sodium citrate, and phosphate salts act as proton acceptors, neutralizing the acidity of a biologic environment (skin, gastric content, urine, etc.) and raising the pH. These agents are used topically or systemically for management of metabolic acidosis, improved muscle contraction, and hyper-acidic conditions (preventing, counteracting, or neutralizing stomach acidity). (NCI04)
An antagonist of histamine H1 receptors.
The phosphate salt of antazoline, an ethylenediamine derivative with histamine H1 antagonistic and sedative properties. Antazoline antagonizes histamine H1 receptor and prevents the typical allergic symptoms caused by histamine activities on capillaries, skin, mucous membranes, gastrointestinal and bronchial smooth muscles. These histamine activities include vasodilation, bronchoconstriction, increased vascular permeability, pain, itching, and spasmodic contractions of gastrointestinal smooth muscles. Antazoline is used to provide symptomatic relieve of allergic symptoms.
Rapid swelling, increased tension, pain, and ischemic necrosis of the muscles of the anterior tibial compartment of the leg, often following excessive PHYSICAL EXERTION.
A pharmacological agent that can kill or prevent the reproduction of parasitic helminths, including nematodes, flukes and tapeworms.
A form of pneumoconiosis caused by inhalation of dust that contains both CARBON and crystalline SILICON DIOXIDE. These foreign matters induce fibrous nodule formation in the lung.
A chronic lung disorder characterized by deposition of coal dust in the lung parenchyma leading to the formation of black nodules and emphysema. It occurs in coal miners.
A natural anthraquinone derivative, anti-psoriatic and anti-inflammatory Anthralin (dithranol) controls skin growth by reducing DNA synthesis and mitotic activity in the hyperplastic epidermis, restoring a normal rate of cell proliferation and keratinization. Used topically in the treatment of psoriasis, dermatoses, and alopecia areata, it is also used in biomedical research due to its effect on EGFR autophosphorylation. (NCI04)
A substance that is based on the structure of anthraquinone and inhibits topoisomerase-II by intercalating into the DNA double strand.
An acute infection caused by the spore-forming bacteria BACILLUS ANTHRACIS. It commonly affects hoofed animals such as sheep and goats. Infection in humans often involves the skin (cutaneous anthrax), the lungs (inhalation anthrax), or the gastrointestinal tract. Anthrax is not contagious and can be treated with antibiotics.
Drugs that are used to treat RHEUMATOID ARTHRITIS.
Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.
A pharmacological agent that can kill or prevent the reproduction of infectious organisms.
Substances used on humans and other animals that destroy harmful microorganisms or inhibit their activity. They are distinguished from DISINFECTANTS, which are used on inanimate objects.
A pharmacological agent that can kill or prevent the reproduction of organisms that cause urinary tract infections (UTIs).
Substances that reduce or suppress INFLAMMATION.
A pharmacological agent that is not a steroid and has potential anti-inflammatory, analgesic, antipyretic and anti-platelet activities. Most nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting the conversion of arachidonic acid to the precursors of prostaglandin and thromboxane by cyclooxygenase enzymes.
Natural or synthetic Anti-ulcer Agents relieve and reduce the symptoms of ulcers in the stomach and upper small intestine, systemically and locally, by reducing gastric secretion (proton pump inhibitors), neutralizing hyperacidity (alkalinizing agents), or improving healing and protecting the mucosa (sucralfate). Recurrent gastric and duodenal ulcers caused by Helicobacter pylori infections are treated with antibiotic therapy.
A type of protein made by B lymphocytes in response to a foreign substance (antigen). Each antibody only binds to a specific antigen, helping to destroy the antigen directly or by assisting white blood cells to destroy the antigen.
Immunoglobulins induced by antigens specific for tumors other than the normally occurring HISTOCOMPATIBILITY ANTIGENS.
A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of ""avidity,"" which refers to the strength of the antigen-antibody bond after formation of reversible complexes.
The phenomenon of immense variability characteristic of ANTIBODIES. It enables the IMMUNE SYSTEM to react specifically against the essentially unlimited kinds of ANTIGENS it encounters. Antibody diversity is accounted for by three main theories: (1) the Germ Line Theory, which holds that each antibody-producing cell has genes coding for all possible antibody specificities, but expresses only the one stimulated by antigen; (2) the Somatic Mutation Theory, which holds that antibody-producing cells contain only a few genes, which produce antibody diversity by mutation; and (3) the Gene Rearrangement Theory, which holds that antibody diversity is generated by the rearrangement of IMMUNOGLOBULIN VARIABLE REGION gene segments during the differentiation of the ANTIBODY-PRODUCING CELLS.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Agents used to treat tapeworm infestations in man or animals.
Substances used to lower plasma CHOLESTEROL levels.
Drugs used to prevent SEIZURES or reduce their severity.
A pharmacological agent that acts on neurotransmitter signaling pathways to alleviate the symptoms of depression.
Mood-stimulating agents which contain a tricyclic structure and are used primarily in the treatment of affective disorders and related conditions. This group of agents appear to act through brain catecholamine systems.
A pharmacological agent that may ameliorate the symptoms of diarrhetic illnesses.
Agents counteracting or neutralizing the action of POISONS.
A pharmacological agent that prevents nausea and/or vomiting.
Agents that prevent fibrinolysis or lysis of a blood clot or thrombus. Several endogenous antiplasmins are known. The drugs are used to control massive hemorrhage and in other coagulation disorders.
Natural or synthetic compounds usually administered orally, Antiflatulent Agents relieve or prevent flatulence, excess gas in the stomach and intestines, by adsorbing the gas, stimulating intestinal elimination of gas, or preventing gas formation. Alpha-galactosidase and activated charcoal are used against flatulence. (NCI04)
Agents used to prevent the formation of foam or to treat flatulence or bloat.
Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
Change in the surface ANTIGEN of a microorganism. There are two different types. One is a phenomenon, especially associated with INFLUENZA VIRUSES, where they undergo spontaneous variation both as slow antigenic drift and sudden emergence of new strains (antigenic shift). The second type is when certain PARASITES, especially trypanosomes, PLASMODIUM, and BORRELIA, survive the immune response of the host by changing the surface coat (antigen switching). (From Herbert et al., The Dictionary of Immunology, 4th ed)
Any substance used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Antihypertensive agents include diuretics, alpha-adrenergic and beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents.
Immunoglobulins raised xenogeneically against lymphocyte populations. It is used both as a test for histocompatibility and in conjunction with other immunosuppressive agents to suppress rejection of grafts or organ transplants.
Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)
An antineoplastic agent with a structural similarity to a natural substance that can replace that substance in a normal biochemical pathway and interfere with the normal metabolic processes of cells.
Antimetabolites that are useful in cancer chemotherapy.
Agents that arrest cells in MITOSIS, most notably TUBULIN MODULATORS.
A schistosomicide possibly useful against other parasites. It has irritant emetic properties and may cause lethal cardiac toxicity among other adverse effects.
Antimony complex where the metal may exist in either the pentavalent or trivalent states. The pentavalent gluconate is used in leishmaniasis. The trivalent gluconate is most frequently used in schistosomiasis.
Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.
Substances used in the treatment or control of nematode infestations. They are used also in veterinary practice.
A substance that inhibits the maturation, growth or spread of tumor cells.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
A group of organic or inorganic substances capable of preventing the genotoxic and carcinogenic effects of free-radical compounds. Antioxidants bind to and neutralize ('scavenge') free radicals, thereby transforming them into non-toxic compounds and blocking their genotoxic and carcinogenic effects. This class of agents includes the vitamins C and E, the carotenoids, and selenium. Organic antioxidants are found in high concentrations in fruits, seeds and vegetables. (NCI04)
An oligopeptide produced by various bacteria which acts as a protease inhibitor.
Any agent that is effective against infections caused by parasitic organisms and is able to inhibit their growth or kill them. This class consists of anthelmintics and antiprotozoals.
Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists.
A member of the serpin superfamily found in plasma that inhibits the lysis of fibrin clots which are induced by plasminogen activator. It is a glycoprotein, molecular weight approximately 70,000 that migrates in the alpha 2 region in immunoelectrophoresis. It is the principal plasmin inactivator in blood, rapidly forming a very stable complex with plasmin.
Agents used to treat cestode, trematode, or other flatworm infestations in man or animals.
A pharmacological agent that can kill or prevent the reproduction of parasitic protozoans.
Agents, usually topical, that relieve itching (pruritus).
Drugs that are used to reduce body temperature in fever.
An analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29)
Agents used to prevent or reverse the pathological events leading to sickling of erythrocytes in sickle cell conditions.
A disorder characterized by a pervasive pattern of disregard for and violation of the rights of others that is manifested in childhood or early adolescence. (adapted from DSM-IV)
Agents, either mechanical or chemical, which destroy spermatozoa in the male genitalia and block spermatogenesis.
A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.
Endogenous factors and drugs that directly inhibit the action of THROMBIN, usually by blocking its enzymatic activity. They are distinguished from INDIRECT THROMBIN INHIBITORS, such as HEPARIN, which act by enhancing the inhibitory effects of antithrombins.
A purified gamma immunoglobulin (IgG) with immunosuppressive activity. Obtained from animals that have been immunized with human thymocytes, antithymocyte globulin (ATG) specifically recognizes and destroys T lymphocytes. Although not completely understood, the mechanism of action appears to involve T lymphocyte clearance from the circulation and modulation of T lymphocyte activity. Administering ATG with chemotherapy prior to stem cell transplantation may reduce the risk of graft-versus-host (GVH) disease.
Antisera from immunized animals that is purified and used as a passive immunizing agent against specific BACTERIAL TOXINS.
Agents used to treat infections with bacteria of the genus TREPONEMA. This includes SYPHILIS & YAWS.
Agents used to treat trichomonas infections.
Any agent that is active against Mycobacterium tuberculosis and can be used in the treatment of or in the prevention of tuberculosis.
Agents that suppress cough. They act centrally on the medullary cough center. EXPECTORANTS, also used in the treatment of cough, act locally.
Antisera used to counteract poisoning by animal VENOMS, especially SNAKE VENOMS.
Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.
Absence of urine formation. It is usually associated with complete bilateral ureteral (URETER) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present.
A non-neoplastic or neoplastic disorder that affects the anal canal or anal margin. Representative examples of non-neoplastic disorders include hemorrhoids and anal ulcer. Representative examples of neoplastic disorders include carcinoma, lymphoma, and melanoma.
A benign or malignant neoplasm that affects the anal canal or anal margin. Representative examples of benign neoplasms include squamous papilloma and papillary hidradenoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and melanoma.
A congenital abnormality characterized by the persistence of the anal membrane, resulting in a thin membrane covering the normal ANAL CANAL. Imperforation is not always complete and is treated by surgery in infancy. This defect is often associated with NEURAL TUBE DEFECTS; MENTAL RETARDATION; and DOWN SYNDROME.
Apprehension of danger and dread accompanied by restlessness, tension, tachycardia, and dyspnea unattached to a clearly identifiable stimulus.
A category of psychiatric disorders which are characterized by anxious feelings or fear often accompanied by physical symptoms associated with anxiety.
Anxiety due to fantasized injuries to or loss of the genitals.
An anxiety disorder characterized by recurrent excessive distress due to fear of separation from the home or from major attachment figures; the distress is developmentally inappropriate and causes impairment in social, academic, or other areas of functioning.
A sac formation resulting from the localized dilatation of the wall of the aorta.
A syndrome resulting from structural defects of the arteries that arise from the aortic arch. Signs and symptoms include weakness, dizziness, arm numbness, blurred vision and transient ischemic attacks.
A birth defect characterized by the narrowing of the AORTA that can be of varying degree and at any point from the transverse arch to the iliac bifurcation. Aortic coarctation causes arterial HYPERTENSION before the point of narrowing and arterial HYPOTENSION beyond the narrowed portion.
Pathological processes involving any part of the AORTA.
Tearing of the aortic wall generally associated with profuse internal bleeding. []
Supravalvular aortic stenosis (SVAS) is a heart defect that develops before birth. This defect is a narrowing (stenosis) of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). The condition is described as supravalvular because the section of the aorta that is narrowed is located just above the valve that connects the aorta with the heart (the aortic valve). Some people with SVAS also have defects in other blood vessels, most commonly stenosis of the artery from the heart to the lungs (the pulmonary artery). An abnormal heart sound during a heartbeat (heart murmur) can often be heard during a chest exam. If SVAS is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and ultimately heart failure.The severity of SVAS varies considerably, even among family members. Some affected individuals die in infancy, while others never experience symptoms of the disorder.
An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.
Aortic valve prolapse can be diagnosed when either or both of the right or non-coronary aortic valve cusps (seen in the cross sectional echocardiographic long axis view) show backward bowing towards the left ventricle beyond a line joining the points of attachment of the aortic valve leaflets to the annulus. [PMID:4015927]
A pathological constriction that can occur above (supravalvular stenosis), below (subvalvular stenosis), or at the AORTIC VALVE. It is characterized by restricted outflow from the LEFT VENTRICLE into the AORTA.
Inflammation of the aorta. Causes include trauma, infectious disorders, and connective tissue disorders.
A congenital anomaly with an abnormal connection between the aorta and the main pulmonary artery resulting in an aortopulmonary shunt.
An anti-inflammatory agent used in the treatment of rheumatoid arthritis. It also has uricosuric properties and has been used to treat gout.
Absence of the crystalline lens of the eye as a result of a developmental defect. [HPO:probinson]
A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia.
An aphasia characterized by impairment of expressive LANGUAGE (speech, writing, signs) and relative preservation of receptive language abilities (i.e., comprehension). This condition is caused by lesions of the motor association cortex in the FRONTAL LOBE (BROCA AREA and adjacent cortical and white matter regions).
A term referring to the inability to speak. It may result from injuries to the vocal cords or may be functional (psychogenic).
A transient absence of spontaneous respiration.
A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.
A benign or malignant neoplasm involving the appendix.
Acute inflammation of the APPENDIX. Acute appendicitis is classified as simple, gangrenous, or perforated.
Agents that are used to suppress appetite.
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
A class Ib anti-arrhythmia agent used to manage ventricular and supraventricular arrhythmias.
A single chain polypeptide isolated from bovine lung with antifibrinolytic and anti-inflammatory activities. As a broad-spectrum serine protease inhibitor, aprotinin bovine competitively and reversibly inhibits the activity of a number of different esterases and proteases, including trypsin, chymotrypsin, kallikrein, plasmin, tissue plasminogen activator, and tissue and leukocytic proteinases, resulting in attenuation of the systemic inflammatory response (SIR), fibrinolysis, and thrombin generation. This agent also inhibits pro-inflammatory cytokine release and maintains glycoprotein homeostasis.
A general term collectively applied to tumors associated with the APUD CELLS series, irrespective of their specific identification.
A phosphate salt form of vidarabine, a nucleoside analog with activity against herpes simplex virus and varicella zoster virus. Vidarabine is converted to a monophosphate by viral thymidine kinase and is further modified to a triphosphate form by host enzymes. Vidarabine triphosphate directly inhibits DNA polymerase and also acts as a chain terminator in DNA replication.
A triphosphate nucleotide analog that is the metabolized, biologically active form of cytarabine. This metabolite is a competitive inhibitor of DNA synthesis.
Abnormally long and slender fingers (""spider fingers"").
Acute or chronic inflammation of the arachnoid membrane of the meninges most often involving the spinal cord or base of the brain. This term generally refers to a persistent inflammatory process characterized by thickening of the ARACHNOID membrane and dural adhesions. Associated conditions include prior surgery, infections, trauma, SUBARACHNOID HEMORRHAGE, and chemical irritation. Clinical features vary with the site of inflammation, but include cranial neuropathies, radiculopathies, and myelopathies. (From Joynt, Clinical Neurology, 1997, Ch48, p25)
A synthetic prostaglandin E analog that protects the gastric mucosa, prevents ulceration, and promotes healing of peptic ulcers. The protective effect is independent of acid inhibition. It is also a potent inhibitor of pancreatic function and can inhibit the growth of experimental tumors.
A group of viral illnesses that are vectored by arthropods, and that are characterized by increased susceptibility to bleeding diatheses.
A viral infection that is transmitted by an arthropod.
A corneal disease in which there is a deposition of phospholipid and cholesterol in the corneal stroma and anterior sclera.
An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetylcholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands.
Virus diseases caused by the ARENAVIRIDAE.
An essential amino acid in juvenile humans, Arginine is a complex amino acid, often found at active site in proteins and enzymes due to its amine-containing side chain. Arginine may prevent or treat heart and circulatory diseases, combat fatigue, and stimulate the immune system. It also boosts production of nitric oxide, relaxing blood vessels, and treating angina and other cardiovascular problems. Arginine is also an important intermediate in the urea cycle and in detoxification of nitrogenous wastes. (NCI04)
The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.
A reversible organophosphorus cholinesterase inhibitor. It also affects the presynaptic membrane and inhibits membrane postsynaptic cholinergic receptors. The compound had former use as a miotic.
A group of congenital malformations involving the brainstem, cerebellum, upper spinal cord, and surrounding bony structures. Type II is the most common, and features compression of the medulla and cerebellar tonsils into the upper cervical spinal canal and an associated MENINGOMYELOCELE. Type I features similar, but less severe malformations and is without an associated meningomyelocele. Type III has the features of type II with an additional herniation of the entire cerebellum through the bony defect involving the foramen magnum, forming an ENCEPHALOCELE. Type IV is a form a cerebellar hypoplasia. Clinical manifestations of types I-III include TORTICOLLIS; opisthotonus; HEADACHE; VERTIGO; VOCAL CORD PARALYSIS; APNEA; NYSTAGMUS, CONGENITAL; swallowing difficulties; and ATAXIA. (From Menkes, Textbook of Child Neurology, 5th ed, p261; Davis, Textbook of Neuropathology, 2nd ed, pp236-46)
A benign or malignant sex cord-stromal tumor arising from the ovary. It is characterized by the presence of neoplastic Leydig cells. Signs and symptoms include hirsutism, menorrhagia and metrorrhagia. It may be associated with trisomy 8.
A disorder in which there is abnormal electrical activity in the heart.
An electrocardiographic finding in which the sinus rate fluctuates with the respiratory cycle. (CDISC)
An arsenical which has been used as a feed additive for enteric conditions in pigs and poultry. It causes blindness and is ototoxic and nephrotoxic in animals.
Proposed chemotherapeutic agent against filaria and trichomonas.
A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed)
An organoarsenic compound that was commonly used for treating SYPHILIS and other diseases.
The hydrochloride salt form of trihexyphenidyl, a synthetic, substituted piperidine with parasympatholytic activity used mostly in Parkinson's disease. Trihexyphenidyl hydrochloride antagonizes activities of acetylcholine via muscarinic receptors. This balances the cholinergic and dopaminergic activity in the basal ganglia leading to an improvement of classic Parkinson symptoms such as rigidity and tremor. In addition, trihexyphenidyl hydrochloride exerts a direct antispasmodic effect on smooth muscle.
A condition in which there is inadequate blood flow through an artery.
Pathological processes which result in the partial or complete obstruction of ARTERIES. They are characterized by greatly reduced or absence of blood flow through these vessels. They are also known as arterial insufficiency.
Abnormal communication between two ARTERIES that may result from injury or occur as a congenital abnormality.
A vascular disorder characterized by thickening and hardening of the walls of the arteries.
Common occlusive arterial disease which is caused by ATHEROSCLEROSIS. It is characterized by lesions in the innermost layer (ARTERIAL INTIMA) of arteries including the AORTA and its branches to the extremities. Risk factors include smoking, HYPERLIPIDEMIA, and HYPERTENSION.
An abnormal connection between an artery and vein.
Abnormal formation of blood vessels that shunt arterial blood directly into veins without passing through the CAPILLARIES. They usually are crooked, dilated, and with thick vessel walls. A common type is the congenital arteriovenous fistula. The lack of blood flow and oxygen in the capillaries can lead to tissue damage in the affected areas.
An inflammatory process affecting an artery.
Acute or chronic inflammation of JOINTS.
Arthritis, especially of the great toe, as a result of gout. Acute gouty arthritis often is precipitated by trauma, infection, surgery, etc. The initial attacks are usually monoarticular but later attacks are often polyarticular. Acute and chronic gouty arthritis are associated with accumulation of MONOSODIUM URATE in and around affected joints.
Arthritis caused by BACTERIA; RICKETTSIA; MYCOPLASMA; VIRUSES; FUNGI; or PARASITES.
A type of inflammatory arthritis associated with PSORIASIS, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of HLA-B27-associated SPONDYLARTHROPATHY, and the absence of rheumatoid factor.
Rheumatoid arthritis is an inflammatory disease, primarily of the joints, with autoimmune features and a complex genetic component.
A non-progressive finding characterized by multiple joint contractures found throughout the body at birth.
Chronic progressive degeneration of the stress-bearing portion of a joint, with bizarre hypertrophic changes at the periphery. It is probably a complication of a variety of neurologic disorders, particularly TABES DORSALIS, involving loss of sensation, which leads to relaxation of supporting structures and chronic instability of the joint. (Dorland, 27th ed)
A dermal inflammatory reaction produced under conditions of antibody excess, when a second injection of antigen produces intravascular antigen-antibody complexes which bind complement, causing cell clumping, endothelial damage, and vascular necrosis.
Disorders of the quality of speech characterized by the substitution, omission, distortion, and addition of phonemes.
A form of pneumoconiosis caused by inhalation of asbestos fibers which elicit potent inflammatory responses in the parenchyma of the lung. The disease is characterized by interstitial fibrosis of the lung, varying from scattered sites to extensive scarring of the alveolar interstitium.
An infection that is caused by the roundworm Ascaris lumbricoides, many cases of which remain asymptomatic. During the transient larval migratory phase, shortness of breath, fever, and eosinophilia can occur. Depending on the intestinal worm burden, a spectrum of gastrointestinal tract symptoms can occur.
Infection with nematodes of the genus ASCARIDIA. This condition usually occurs in fowl, often manifesting diarrhea.
Accumulation of fluid in the peritoneal cavity.
A natural water-soluble vitamin (Vitamin C). Ascorbic acid is a potent reducing and antioxidant agent that functions in fighting bacterial infections, in detoxifying reactions, and in the formation of collagen in fibrous tissue, teeth, bones, connective tissue, skin, and capillaries. Found in citrus and other fruits, and in vegetables, vitamin C cannot be produced or stored by humans and must be obtained in the diet. (NCI04)
A condition due to a dietary deficiency of ascorbic acid (vitamin C), characterized by malaise, lethargy, and weakness. As the disease progresses, joints, muscles, and subcutaneous tissues may become the sites of hemorrhage. Ascorbic acid deficiency frequently develops into SCURVY in young children fed unsupplemented cow's milk exclusively during their first year. It develops also commonly in chronic alcoholism. (Cecil Textbook of Medicine, 19th ed, p1177)
Aseptic necrosis involving the head and neck of the femur.
A hydrolase enzyme that converts L-asparagine and water to L-aspartate and NH3. EC 3.5.1.1.
Flavoring agent sweeter than sugar, metabolized as PHENYLALANINE and ASPARTIC ACID.
An infection that is caused by Aspergillus.
An immune reaction to aspergillus in patients usually suffering from asthma or cystic fibrosis.
A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life.
An orally administered non-steroidal antiinflammatory agent. Acetylsalicylic acid binds to and acetylates serine residues in cyclooxygenases, resulting in decreased synthesis of prostaglandin, platelet aggregation, and inflammation. This agent exhibits analgesic, antipyretic, and anticoagulant properties.
Astatine. A radioactive halogen with the atomic symbol At, and atomic number 85. Its isotopes range in mass number from 200 to 219 and all have an extremely short half-life. Astatine may be of use in the treatment of hyperthyroidism because it emits ALPHA PARTICLES.
A sign or symptom of weakness and diminished or absent energy and strength.
Eye strain, i.e., a feeling of fatigue or discomfort of the eyes related to 'overuse' of the eyes in activities such as reading or working at the computer and often accompanied by lacrimation or headache. []
A chronic respiratory disease manifested as difficulty breathing due to the narrowing of bronchial passageways.
Asthma attacks following a period of exercise. Usually the induced attack is short-lived and regresses spontaneously. The magnitude of postexertional airway obstruction is strongly influenced by the environment in which exercise is performed (i.e. inhalation of cold air during physical exertion markedly augments the severity of the airway obstruction; conversely, warm humid air blunts or abolishes it).
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions.
A glial tumor of the brain or spinal cord showing astrocytic differentiation. It includes the following clinicopathological entities: pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, and glioblastoma.
A type of ataxia characterized by the impairment of the ability to smoothly perform the elements of a voluntary movement in the appropriate order and speed. With dyssynergia, a voluntary movement appears broken down into its component parts.
Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Chromosomal breakage is a feature. AT cells are abnormally sensitive to killing by ionizing radiation (IR), and abnormally resistant to inhibition of DNA synthesis by ionizing radiation. The latter trait has been used to identify complementation groups for the classic form of the disease (Jaspers et al., 1988). At least 4 of these (A, C, D, and E) map to chromosome 11q23 (Sanal et al., 1990) and are associated with mutations in the ATM gene.
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosome locus) in which pathogenic variants occur.
Absence of air in the entire or part of a lung, such as an incompletely inflated neonate lung or a collapsed adult lung. Pulmonary atelectasis can be caused by airway obstruction, lung compression, fibrotic contraction, or other factors.
A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to PROPRANOLOL, but without a negative inotropic effect.
A condition characterized by patchy atheromas or atherosclerotic plaques which develop in the walls of medium-sized and large arteries and can lead to arterial stenosis with reduced or blocked blood flow.
A dyskinesia characterized by an inability to maintain the fingers, toes, tongue, or other body parts in a stable position, resulting in continuous slow, sinusoidal, and flowing involuntary movements. This condition is frequently accompanied by CHOREA, where it is referred to as choreoathetosis. Athetosis may occur as a manifestation of BASAL GANGLIA DISEASES or DRUG TOXICITY. (From Adams et al., Principles of Neurology, 6th ed, p76)
A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents.
A synthetic dibenzensulfonate derivative muscle relaxant, Atracurium Besylate acts as a non-depolarizing neuromuscular blocking agent, with short to intermediary duration of action and no significant cardiovascular effects. Not dependent on kidney function for elimination, it provides clinical advantages over other non-depolarizing, neuromuscular blocking agents. (NCI04)
A disorder characterized by an electrocardiographic finding of a supraventricular arrhythmia characterized by the replacement of consistent P waves by rapid oscillations or fibrillatory waves that vary in size, shape and timing and are accompanied by an irregular ventricular response. (CDISC)
A disorder characterized by an electrocardiographic finding of an organized, regular atrial rhythm with atrial rate of 240-340 beats per minute. Multiple P waves typically appear in the inferior leads in a saw tooth-like pattern between the QRS complexes. (CDISC)
An electrocardiographic finding of delayed or blocked cardiac electrical impulse conduction from the atria to the ventricles at the level of the atrioventricular node.
A synthetically-derived form of the endogenous alkaloid isolated from the plant Atropa belladonna. Atropine functions as a sympathetic, competitive antagonist of muscarinic cholinergic receptors, thereby abolishing the effects of parasympathetic stimulation. This agent may induce tachycardia, inhibit secretions, and relax smooth muscles. (NCI04)
The sulfate salt of a belladonna alkaloid derivative and the levorotatory form of racemic atropine isolated from the plants Hyoscyamus niger or Atropa belladonna, which exhibits anticholinergic activity. Hyoscyamine functions as a non-selective, competitive antagonist of muscarinic receptors, thereby inhibiting the parasympathetic activities of acetylcholine on the salivary, bronchial, and sweat glands, as well as the eye, heart, bladder, and gastrointestinal tract. These inhibitory effects cause a decrease in saliva, bronchial mucus, gastric juices, and sweat. Furthermore, its inhibitory action on smooth muscle prevents bladder contraction and decreases gastrointestinal motility.
Disorders of hearing or auditory perception due to pathological processes of the AUDITORY PATHWAYS in the CENTRAL NERVOUS SYSTEM. These include CENTRAL HEARING LOSS and AUDITORY PERCEPTUAL DISORDERS.
A disorder characterized by the inability of the brain to properly interpret or process the auditory signals it receives from the anatomic structures of the ear.
An oral chrysotherapeutic agent for the treatment of rheumatoid arthritis. Its exact mechanism of action is unknown, but it is believed to act via immunological mechanisms and alteration of lysosomal enzyme activity. Its efficacy is slightly less than that of injected gold salts, but it is better tolerated, and side effects which occur are potentially less serious.
An electrocardiographic finding in which the electrical activity of the atria and ventricles are independent of one another. (CDISC)
A dye which inhibits protein biosynthesis at the initial stages. The ammonium salt (aluminon) is a reagent for the colorimetric estimation of aluminum in water, foods, and tissues.
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; and AUTS19, associated with mutation in the EIF4E gene (133440) on chromosome 4q23. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.
A disorder resulting from loss of function or tissue destruction of an organ or multiple organs, arising from humoral or cellular immune responses of the individual to his own tissue constituents. It may be systemic (e.g., systemic lupus erythematosus), or organ specific, (e.g., thyroiditis).
Autoimmune Status; the state of a person's health in regard to autoimmune disease or antibody presence.
The destruction of organism cells or tissues by the organism's own enzymes or processes.
Automatic, mechanical, and apparently undirected behavior which is outside of conscious control.
Agents affecting the function of, or mimicking the actions of, the autonomic nervous system and thereby having an effect on such processes as respiration, circulation, digestion, body temperature regulation, certain endocrine gland secretions, etc.
A group of transmissible viral diseases of chickens and turkeys. Liver tumors are found in most forms, but tumors can be found elsewhere.
Connective tissue tumors, affecting primarily fowl, that are usually caused by avian sarcoma viruses.
A disorder characterized by an enduring pattern of avoidance of social situations and interpersonal contact due to overwhelming feelings of social inadequacy and a hypersensitivity to negative evaluation or rejection.
A sterol derivative of cholesterol with two nitrogen atoms replacing two carbon atoms that acts as a hypocholesteremic agent by blocking delta-24-reductase. Azacosterol has the unintended side effect of causing myotonia.
A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
A purine analogue with potential antineoplastic activity. 8-Azaguanine interferes with the modification of transfer ribonucleic acid (tRNA) by competing with guanine for incorporation into tRNA catalyzed by the enzyme tRNA-guanine ribosyltransferase (tRNA-guanine transglycosylase). Altered guanine modification of tRNA has been implicated in cellular differentiation and neoplastic transformation. 8-Azaguanine also inhibits the formation of 43S and 80S initiation complexes, thereby interfering with initiation of translation and inhibiting protein synthesis. This agent inhibits tumor cell growth and stimulates cell differentiation. (NCI04)
A butyrophenone used in the treatment of PSYCHOSES.
A naturally occurring serine derivative diazo compound with antineoplastic properties, Azaserine functions as a purine antagonist and glutamine analogue (glutamine amidotransferase inhibitor) that competitively inhibits pathways in which glutamine is metabolized. An antibiotic and antitumor agent, Azaserine is used in clinical studies as a potential antineoplastic agent. (NCI04)
A purine analogue with cytotoxic and immunosuppressive activity. Azathioprine is a prodrug that is converted by hepatic xanthine oxidase to its active metabolite 6-mercaptopurine (6-MP). 6-MP is further metabolized by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) into 6-thioguanosine-5'-phosphate (6-thio-GMP) and 6-thioinosine monophosphate (6-thio-IMP), both inhibit nucleotide conversions and de novo purine synthesis. This leads to inhibition of DNA, RNA, and protein synthesis. As a result, cell proliferation may be inhibited, particularly in lymphocytes and leukocytes.
A synthetic triazine analogue of uridine with antimetabolite activity. 6-azauridine inhibits de novo pyrimidine synthesis and DNA synthesis and is converted intracellularly into mono, di, and triphosphate derivatives, which incorporate into RNA and inhibit protein synthesis.
A condition of having no sperm present in the ejaculate (SEMEN).
A group of tick-borne diseases of mammals including ZOONOSES in humans. They are caused by protozoa of the genus BABESIA, which parasitize erythrocytes, producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by the deer tick IXODES SCAPULARIS.
Acute or chronic pain located in the posterior regions of the THORAX; LUMBOSACRAL REGION; or the adjacent regions.
An early stage of diabetic retinopathy that is characterized by retinal hemorrhage and exudate, but without proliferation of the blood vessels.
A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.
Presence of viable bacteria in the blood. []
Infections caused by bacteria and fungi, general, specified, or unspecified.
An acute infectious disorder that is caused by gram positive or gram negative bacteria; representative examples include pneumococcal, streptococcal, salmonella, and meningeal infections.
Acute infection of the lung parenchyma caused by bacteria (e.g., Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila). Signs and symptoms include productive cough, fever, chills, shortness of breath, and chest pain.
A vaccine derived from bacteria whether killed, attenuated or live that is used for prophylaxis or treatment against infection.
The presence of bacteria in the urine which is normally bacteria-free. These bacteria are from the URINARY TRACT and are not contaminants of the surrounding tissues. Bacteriuria can be symptomatic or asymptomatic. Significant bacteriuria is an indicator of urinary tract infection.
Infections with bacteria of the genus BACTEROIDES.
A diffuse parenchymal lung disease caused by inhaled dust from processing SUGARCANE (bagasse), usually in the manufacturing of wallboard.
An infectious or non-infectious inflammatory process that affects the glans penis. Symptoms include redness and pain of the glans penis and foreskin and discharge.
A parasitic protozoal infection caused by Balantidium coli that involves the large intestinal mucosa. Signs and symptoms include nausea, vomiting, diarrhea, abdominal pain, fever, headache and weight loss.
A form of chronic interstitial nephritis that is endemic to limited areas of BULGARIA, the former YUGOSLAVIA, and ROMANIA. It is characterized by a progressive shrinking of the KIDNEYS that is often associated with uroepithelial tumors.
A long-acting barbiturate that depresses most metabolic processes at high doses. It is used as a hypnotic and sedative and may induce dependence. Barbital is also used in veterinary practice for central nervous system depression.
A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are GABA MODULATORS used as HYPNOTICS AND SEDATIVES, as ANESTHETICS, or as ANTICONVULSANTS.
Barrett esophagus, or Barrett metaplasia, describes the phenotypic change of normal esophageal squamous epithelium to a columnar and intestinal-type epithelium. This metaplastic change is important because patients with Barrett esophagus have an increased risk of esophageal adenocarcinoma. The main cause of Barrett metaplasia is gastroesophageal reflux (GER; 109350). The retrograde movement of acid and bile salts from the stomach into the esophagus in this disease causes prolonged injury to the esophageal epithelium and induces chronic esophagitis, which in turn is believed to trigger the pathologic changes (summary by Wong et al., 2005).
Distension of the Bartholin gland duct caused by an accumulation of mucus in the duct, usually as a result of obstruction of the gland duct orifice.
A gram-negative bacterial infection caused by Bartonella bacilliformis. It is transmitted by ticks, flies and mosquitoes. Signs and symptoms include fever, headache, muscle pain, enlargement of the lymph nodes and anemia.
Infections with bacteria of the family BARTONELLACEAE.
Bartter syndrome is a group of very similar kidney disorders that cause an imbalance of potassium, sodium, chloride, and related molecules in the body.In some cases, Bartter syndrome becomes apparent before birth. The disorder can cause polyhydramnios, which is an increased volume of fluid surrounding the fetus (amniotic fluid). Polyhydramnios increases the risk of premature birth.Beginning in infancy, affected individuals often fail to grow and gain weight at the expected rate (failure to thrive). They lose excess amounts of salt (sodium chloride) in their urine, which leads to dehydration, constipation, and increased urine production (polyuria). In addition, large amounts of calcium are lost through the urine (hypercalciuria), which can cause weakening of the bones (osteopenia). Some of the calcium is deposited in the kidneys as they are concentrating urine, leading to hardening of the kidney tissue (nephrocalcinosis). Bartter syndrome is also characterized by low levels of potassium in the blood (hypokalemia), which can result in muscle weakness, cramping, and fatigue. Rarely, affected children develop hearing loss caused by abnormalities in the inner ear (sensorineural deafness).Two major forms of Bartter syndrome are distinguished by their age of onset and severity. One form begins before birth (antenatal) and is often life-threatening. The other form, often called the classical form, begins in early childhood and tends to be less severe. Once the genetic causes of Bartter syndrome were identified, researchers also split the disorder into different types based on the genes involved. Types I, II, and IV have the features of antenatal Bartter syndrome. Because type IV is also associated with hearing loss, it is sometimes called antenatal Bartter syndrome with sensorineural deafness. Type III usually has the features of classical Bartter syndrome.
Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple jaw keratocysts, frequently beginning in the second decade of life, and/or basal cell carcinomas (BCCs) usually from the third decade onward. Approximately 60% of individuals have a recognizable appearance with macrocephaly, frontal bossing, coarse facial features, and facial milia. Most individuals have skeletal anomalies (e.g., bifid ribs, wedge-shaped vertebrae). Ectopic calcification, particularly in the falx, is present in more than 90% of affected individuals by age 20 years. Cardiac and ovarian fibromas occur in approximately 2% and 20% of individuals respectively. Approximately 5% of all children with NBCCS develop medulloblastoma (primitive neuroectodermal tumor), generally the desmoplastic subtype. The risk of developing medulloblastoma is substantially higher in individuals with an SUFU pathogenic variant (33%) than in those with a PTCH1 pathogenic variant (<2%). Peak incidence is at age one to two years. Life expectancy in NBCCS is not significantly different from average.
A syndrome which occurs as a result of the occlusion of the basilar artery. It may be caused by atherosclerosis, embolism or hemorrhage. Clinical signs include dizziness, headache, vomiting, hemiparesis or hemiplegia, dysarthria, dysphagia, blurred vision and loss of consciousness. The clinical course is variable and is dependent upon the extent of the occlusion and the location of the clot along the basilar artery which determines the resultant neurologic impairment. Prognosis is dismal in cases where a complete occlusion occurs with rapid deterioration of neurological function.
A clinical condition resulting from repeated physical and psychological injuries inflicted on a child by the parents or caregivers.
A vaccine containing bacillus Calmette-Guerin (BCG), an attenuated strain of Mycobacterium bovis, with non-specific immunoadjuvant and immunotherapeutic activities. Although the mechanism of its anti-tumor activity is unclear, immunization with BCG vaccine likely activates a Th1 cytokine response that includes the induction of interferon. Vaccination with BCG vaccine may be immunoprotective against infection with Mycobacterium tuberculosis.
Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues.
A synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. After cell surface receptor attachment and cell entry, beclomethasone enters the nucleus where it binds to and activates specific nuclear receptors, resulting in an altered gene expression and inhibition of proinflammatory cytokine production.
The dipropionate ester of a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. After cell surface receptor attachment and cell entry, beclomethasone enters the nucleus where it binds to and activates specific nuclear receptors, resulting in an altered gene expression and inhibition of proinflammatory cytokine production.
A specific behavioral problem that occurs in persistent patterns and characteristic clusters and that causes clinically significant impairment.
A disorder characterized by behavioral and/or psychological abnormalities, often accompanied by physical symptoms. The symptoms may cause clinically significant distress or impairment in social and occupational areas of functioning. Representative examples include anxiety disorders, cognitive disorders, mood disorders and schizophrenia.
Observable manifestations of impaired psychological functioning.
Behçet disease is an inflammatory condition that affects many parts of the body. The health problems associated with Behçet disease result from widespread inflammation of blood vessels (vasculitis). This inflammation most commonly affects small blood vessels in the mouth, genitals, skin, and eyes.Painful mouth sores called aphthous ulcers are usually the first sign of Behçet disease. These sores can occur on the lips, tongue, inside the cheeks, the roof of the mouth, the throat, and the tonsils. The ulcers look like common canker sores, and they typically heal within one to two weeks. About 75 percent of all people with Behçet disease develop similar ulcers on the genitals. These ulcers occur most frequently on the scrotum in men and on the labia in women.Behçet disease can also cause painful bumps and sores on the skin. Most affected individuals develop pus-filled bumps that resemble acne. These bumps can occur anywhere on the body. Some affected people also have red, tender nodules called erythema nodosum. These nodules usually develop on the legs but can also occur on the arms, face, and neck.An inflammation of the eye called uveitis is found in more than half of people with Behçet disease. Eye problems are more common in younger people with the disease and affect men more often than women. Uveitis can result in blurry vision and an extreme sensitivity to light (photophobia). Rarely, inflammation can also cause eye pain and redness. If untreated, the eye problems associated with Behçet disease can lead to blindness.Joint involvement is also common in Behçet disease. Often this affects one joint at a time, with each affected joint becoming swollen and painful and then getting better.Less commonly, Behçet disease can affect the brain and spinal cord (central nervous system), gastrointestinal tract, large blood vessels, heart, lungs, and kidneys. Central nervous system abnormalities can lead to headaches, confusion, personality changes, memory loss, impaired speech, and problems with balance and movement. Involvement of the gastrointestinal tract can lead to a hole in the wall of the intestine (intestinal perforation), which can cause serious infection and may be life-threatening.The signs and symptoms of Behçet disease usually begin in a person's twenties or thirties, although they can appear at any age. Some affected people have relatively mild symptoms that are limited to sores in the mouth and on the genitals. Others have more severe symptoms affecting various parts of the body, including the eyes and the vital organs. The features of Behçet disease typically come and go over a period of months or years. In most affected individuals, the health problems associated with this disorder improve with age.
Alkaloids obtained from various plants, especially the deadly nightshade (Atropa belladonna), variety acuminata; atropine, hyoscyamine and scopolamine are classical, specific antimuscarinic agents with many pharmacologic actions; used mainly as antispasmodics.
A CNS stimulant that is used to induce convulsions in experimental animals. It has also been used as a respiratory stimulant and in the treatment of barbiturate overdose.
A centrally acting muscarinic antagonist. Benactyzine has been used in the treatment of depression and is used in research to investigate the role of cholinergic systems on behavior.
The hydrochloride salt form of diphenhydramine, an ethanolamine and first-generation histamine antagonist with anti-allergic activity. Diphenhydramine hydrochloride competitively blocks H1receptors, thereby preventing the actions of histamine on bronchial smooth muscle, capillaries, and gastrointestinal (GI) smooth muscle. This prevents histamine-induced bronchoconstriction, vasodilation, increased capillary permeability, and GI smooth muscle spasms.
The presence of free monoclonal immunoglobulin light chains in the urine.
A vasodilator agent found to be effective in a variety of peripheral circulation disorders. It has various other potentially useful pharmacological effects. Its mechanism may involve block of calcium channels.
A long-acting agent, also known as bendrofluazide, belonging to the class of thiazide diuretics with antihypertensive activity.
A non-metastasizing neoplasm arising from the wall of the colon.
A non-metastasizing neoplasm that arises from the lower jaw bone.
A non-metastasizing neoplasm that arises from the ovary. Representative examples include serous cystadenoma, mucinous cystadenoma, clear cell adenofibroma, benign Brenner tumor, thecoma, and fibroma.
Abnormal growth of the cells that comprise the tissues of the skin, without any evidence of malignancy.
The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine out of the body. As men age, their prostate grows bigger. If it gets too large, it can cause problems. An enlarged prostate is also called benign prostatic hyperplasia (BPH). Most men will get BPH as they get older. Symptoms often start after age 50. BPH is not cancer, and it does not seem to increase your chance of getting prostate cancer. But the early symptoms are the same. Check with your doctor if you have. -A frequent and urgent need to urinate, especially at night. -Trouble starting a urine stream or making more than a dribble. -A urine stream that is weak, slow, or stops and starts several times. -The feeling that you still have to go, even just after urinating. -Small amounts of blood in your urine. Severe BPH can cause serious problems over time, such as urinary tract infections, and bladder or kidney damage. If it is found early, you are less likely to develop these problems. Tests for BPH include a digital rectal exam, blood and imaging tests, a urine flow study, and examination with a scope called a cystoscope. Treatments include watchful waiting, medicines, nonsurgical procedures, and surgery. NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
A butyrophenone with general properties similar to those of HALOPERIDOL. It has been used in the treatment of aberrant sexual behavior. (From Martindale, The Extra Pharmacopoeia, 30th ed, p567)
An inhibitor of DOPA DECARBOXYLASE that does not enter the central nervous system. It is often given with LEVODOPA in the treatment of parkinsonism to prevent the conversion of levodopa to dopamine in the periphery, thereby increasing the amount that reaches the central nervous system and reducing the required dose. It has no antiparkinson actions when given alone.
A colloidal, hydrated aluminum silicate that swells 12 times its dry size when added to water.
A mixture of alkylbenzyldimethylammonium compounds. It is a bactericidal quaternary ammonium detergent used topically in medicaments, deodorants, mouthwashes, as a surgical antiseptic, and as a as preservative and emulsifier in drugs and cosmetics.
Compounds with BENZENE fused to AZEPINES.
Uricosuric that acts by increasing uric acid clearance. It is used in the treatment of gout.
An organochlorine insecticide made up of greater than 99% gamma-Hexachlorocyclohexane. It has been used as a pediculicide and scabicide, and shown to cause cancer.
Bactericidal cationic quaternary ammonium surfactant used as a topical anti-infective agent. It is an ingredient in medicaments, deodorants, mouthwashes, etc., and is used to disinfect apparatus, etc., in the food processing and pharmaceutical industries, in surgery, and also as a preservative. The compound is toxic orally as a result of neuromuscular blockade.
A surface anesthetic that acts by preventing transmission of impulses along NERVE FIBERS and at NERVE ENDINGS.
Drugs from this chemical class are used for their central nervous system depressant properties including sedation, facilitation of sleep, seizure control, general anesthesia, anxiolytic, amnestic, and for detoxification from similar (cross tolerant) drugs
Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered.
A white crystalline compound prepared by condensation of benzaldehyde in potassium cyanide and used in organic syntheses. This should not be confused with benzoin gum from STYRAX.
Selective renal carbonic anhydrase inhibitor. It may also be of use in certain cases of respiratory failure.
An aniline dye used as a disinfectant and an antiseptic agent. It is weakly fluorescing and binds specifically to certain proteins.
A peroxide derivative that has been used topically for BURNS and as a dermatologic agent in the treatment of ACNE and POISON IVY DERMATITIS. It is used also as a bleach in the food industry.
A sympathomimetic agent with properties similar to DEXTROAMPHETAMINE. It is used in the treatment of obesity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1222)
A centrally active muscarinic antagonist that has been used in the symptomatic treatment of PARKINSON DISEASE. Benztropine also inhibits the uptake of dopamine.
A benzyl-indazole having analgesic, antipyretic, and anti-inflammatory effects. It is used to reduce post-surgical and post-traumatic pain and edema and to promote healing. It is also used topically in treatment of RHEUMATIC DISEASES and INFLAMMATION of the mouth and throat.
A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with LIDOCAINE injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring.
A long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist.
An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal.
A disease caused by a deficiency of thiamine (vitamin B1) and characterized by polyneuritis, cardiac pathology, and edema. The epidemic form is found primarily in areas in which white (polished) rice is the staple food, as in Japan, China, the Philippines, India, and other countries of southeast Asia. (Dorland, 27th ed)
Bernard-Soulier syndrome is an autosomal recessive bleeding disorder caused by a defect in or deficiency of the platelet membrane von Willebrand factor (VWF; 613160) receptor complex, glycoprotein Ib (GP Ib). GP Ib is composed of 4 subunits encoded by 4 separate genes: GP1BA, GP1BB, GP9, and GP5 (173511). Genetic Heterogeneity of Platelet-Type Bleeding Disorders Inherited platelet disorders are a heterogeneous group of bleeding disorders affecting platelet number, function, or both. Functional defects can involve platelet receptors, signaling pathways, cytoskeletal proteins, granule contents, activation, or aggregation (review by Cox et al., 2011 and Nurden and Nurden, 2011). Platelet-type bleeding disorders include Bernard-Soulier syndrome (BDPLT1); Glanzmann thrombasthenia (BDPLT2; 273800), caused by mutation in the ITGA2B (607759) or ITGB3 (173470) gene; pseudo-von Willebrand disease (BDPLT3; 177820), caused by mutation in the GP1BA gene (606672); gray platelet syndrome (BDPLT4; 139090), caused by mutation in the NBEAL2 gene (614169); Quebec platelet disorder (BDPLT5; 601709), caused by tandem duplication of the PLAU gene (191840); May-Hegglin anomaly (BDPLT6; 155100), caused by mutation in the MYH9 gene (160775); Scott syndrome (BDPLT7; 262890), caused by mutation in the TMEM16F gene (608663); BDPLT8 (609821), caused by mutation in the P2RY12 gene (600515); BDPLT9 (614200), associated with deficiency of the glycoprotein Ia/IIa receptor (see ITGA2; 192974); glycoprotein IV deficiency (BDPLT10; 608404), caused by mutation in the CD36 gene (173510); BDPLT11 (614201), caused by mutation in the GP6 gene (605546); BDPLT12 (605735), associated with a deficiency of platelet COX1 (176805); susceptibility to BDPLT13 (614009), caused by mutation in the TBXA2R gene (188070); BDPLT14 (614158), associated with deficiency of thromboxane synthetase (TBXAS1; 274180); BDPLT15 (615193), caused by mutation in the ACTN1 gene (102575); BDPLT16 (187800), caused by mutation in the ITGA2B (607759) or ITGB3 (173470) gene; BDPLT17 (187900), caused by mutation in the GFI1B gene (604383); BDPLT18 (615888), caused by mutation in the RASGRP2 gene (605577); BDPLT19 (616176), caused by mutation in the PRKACG gene (176893); BDPLT20 (616913), caused by mutation in the SLFN14 gene (614958); and BDPLT21 (617443), caused by mutation in the FLI1 gene (193067). See reviews by Rao (2003), Cox et al. (2011), and Nurden and Nurden (2011). For a discussion of the genetic heterogeneity of hereditary thrombocytopenia, see THC1 (313900).
A small cerebral artery aneurysm, characterized by a saccular appearance, that typically forms at the junction of vessels in the circle of Willis.
A group of enzymes that catalyzes the hydrolysis of terminal, non-reducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause GANGLIOSIDOSIS, GM1.
Beta-thalassemia (ß-thalassemia) is characterized by reduced synthesis of the hemoglobin subunit beta (hemoglobin beta chain) that results in microcytic hypochromic anemia, an abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of hemoglobin A (HbA) on hemoglobin analysis. Individuals with thalassemia major have severe anemia and hepatosplenomegaly; they usually come to medical attention within the first two years of life. Without treatment, affected children have severe failure to thrive and shortened life expectancy. Treatment with a regular transfusion program and chelation therapy, aimed at reducing transfusion iron overload, allows for normal growth and development and may improve the overall prognosis. Individuals with thalassemia intermedia present later and have milder anemia that does not require regular treatment with blood transfusion. These individuals are at risk for iron overload secondary to increased intestinal absorption of iron as a result of ineffective erythropoiesis.
A natural tocopherol with less antioxidant activity than alpha-tocopherol. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. As in GAMMA-TOCOPHEROL, it also has three methyl groups on the 6-chromanol nucleus but at different sites.
A histamine analog and H1 receptor agonist that serves as a vasodilator. It is used in MENIERE DISEASE and in vascular headaches but may exacerbate bronchial asthma and peptic ulcers.
A naturally occurring compound that has been of interest for its role in osmoregulation. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1341)
A glucocorticoid given orally, parenterally, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Its lack of mineralocorticoid properties makes betamethasone particularly suitable for treating cerebral edema and congenital adrenal hyperplasia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p724)
A cardioselective beta-1-adrenergic antagonist with no partial agonist activity.
A histamine H2 agonist used clinically to test gastric secretory function.
Quaternary ammonium compounds that include BETHANECHOL.
A guanidinium antihypertensive agent that acts by blocking adrenergic transmission. The precise mode of action is not clear.
An agonist of peroxisome proliferator-activated receptor alpha (PPARalpha) with antilipidemic activity. Bezafibrate decreases triglyceride levels, increases high density lipoprotein (HDL) cholesterol levels, and decreases total and low density lipoprotein (LDL) cholesterol levels.
Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.
An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.
Derivatives of biguanide (the structure formula HN(C(NH)NH2)2) that are primarily used as oral HYPOGLYCEMIC AGENTS for the treatment of DIABETES MELLITUS, TYPE 2 and PREDIABETES.
A non-neoplastic or neoplastic disorder that affects the intrahepatic or extrahepatic bile ducts. Representative examples of non-neoplastic disorders include cholangitis and biliary atresia. Representative examples of neoplastic disorders include extrahepatic bile duct adenoma and cholangiocarcinoma.
A benign or malignant neoplasm that affects the intrahepatic or extrahepatic bile ducts. Representative examples of benign neoplasms include bile duct adenoma and extrahepatic bile duct lipoma. Representative examples of malignant neoplasms include intrahepatic and extrahepatic cholangiocarcinoma.
Impairment of bile flow due to obstruction in large bile ducts outside the liver.
Retrograde bile flow. Reflux of bile can be from the duodenum to the stomach (DUODENOGASTRIC REFLUX); to the esophagus (GASTROESOPHAGEAL REFLUX); or to the PANCREAS.
A congenital disorder characterized by blockage or absence of the intrahepatic or extrahepatic bile ducts.
A motility disorder characterized by biliary COLIC, absence of GALLSTONES, and an abnormal GALLBLADDER ejection fraction. It is caused by gallbladder dyskinesia and/or SPHINCTER OF ODDI DYSFUNCTION.
Abnormal passage in any organ of the biliary tract or between biliary organs and other organs.
A tumor (abnormal growth of tissue) of the biliary system. [HPO:probinson]
Presence of conjugated bilirubin in the urine. [OHSU:jpgourdine]
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Any inability to efficiently utilize and/or sustain binocular vision.
Naturally occurring flavone or coumarin derivatives having the activity of the so-called vitamin P, notably rutin and esculin.
A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology.
Complex pharmaceutical substances, preparations, or matter derived from organisms usually obtained by biological methods or assay.
Any substance that induces, enhances, restores or suppresses the host's immune system, or an agent that utilizes or is derived from a component of the immune system.
A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.
A muscarinic antagonist that has effects in both the central and peripheral nervous systems. It has been used in the treatment of arteriosclerotic, idiopathic, and postencephalitic parkinsonism. It has also been used to alleviate extrapyramidal symptoms induced by phenothiazine derivatives and reserpine.
A disorder of the brain that causes unusual shifts in mood, energy, activity levels and the ability to carry out day-to-day tasks. Often these moods range and shift from periods of elation and energized behavior to those of hopelessness and depression.
The depressive stage of bipolar disorder.
Diseases of birds not considered poultry, therefore usually found in zoos, parks, and the wild. The concept is differentiated from POULTRY DISEASES which is for birds raised as a source of meat or eggs for human consumption, and usually found in barnyards, hatcheries, etc.
A form of alveolitis or pneumonitis due to an acquired hypersensitivity to inhaled avian antigens, usually proteins in the dust of bird feathers and droppings.
Indicates the sequence of a biologic entity's birth in the family group.
A diphenylmethane stimulant laxative used for the treatment of CONSTIPATION and for bowel evacuation. (From Martindale, The Extra Pharmacopoeia, 30th ed, p871)
A hydroxycoumarin originally isolated from molding sweet-clover hay, with anticoagulant and vitamin K depletion activities. Dicumarol is a competitive inhibitor of vitamin K epoxide reductase; thus, it inhibits vitamin K recycling and causes depletion of active vitamin K in blood. This prevents the formation of the active form of prothrombin and several other coagulant enzymes, and inhibits blood clotting.
A metallic element that has the atomic symbol Bi, and atomic number 83. Its principal isotope is Bismuth 209.
A complication of MALARIA, FALCIPARUM characterized by the passage of dark red to black urine.
Buildups of minerals that form in the urinary bladder.
Bladder cancer is a disease in which certain cells in the bladder become abnormal and multiply without control or order. The bladder is a hollow, muscular organ in the lower abdomen that stores urine until it is ready to be excreted from the body. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called transitional cell carcinoma (TCC).Bladder cancer may cause blood in the urine, pain during urination, frequent urination, or the feeling that one needs to urinate without results. These signs and symptoms are not specific to bladder cancer, however. They also can be caused by noncancerous conditions such as infections.
A non-neoplastic or neoplastic disorder affecting the urinary bladder. A representative example of non-neoplastic bladder disorder is bacterial bladder infection. A representative example of neoplastic bladder disorder is bladder carcinoma.
A birth defect in which the URINARY BLADDER is malformed and exposed, inside out, and protruded through the ABDOMINAL WALL. It is caused by closure defects involving the top front surface of the bladder, as well as the lower abdominal wall; SKIN; MUSCLES; and the pubic bone.
An abnormal communication between the urinary bladder and another organ or anatomic site.
Blockage of the opening between the bladder and the urethra resulting in the reduction or prevention of the urine flow from the bladder into the urethra.
A benign or malignant, primary or metastatic neoplasm of the bladder. - 2003
An inability to completely empty the urinary bladder during the process of urination owing to a neurological condition.
An advanced phase of chronic myelogenous leukemia. It is characterized by: 1. the presence of blasts in the peripheral blood or bone marrow that are at least 20% of the peripheral blood white cells or of the nucleated cells in the bone marrow respectively, or 2. an extramedullary proliferation of blasts, and/or 3. when there are large aggregates and clusters of blasts in the bone marrow biopsy specimen (adapted from WHO, 2001).
A fungal infection caused by inhalation of spores of Blastomyces dermatitidis. It presents with flu-like symptoms including fever, chills, cough, pleuritic chest pain and myalgias. It may lead to a chronic granulomatous pulmonary infection and disseminate to other anatomic sites including skin, nervous system and bones.
A pulmonary disease resulting from infection with Blastomyces dermatitidis, which is prevalent in North America.
Inflammation of the eyelids near the eyelashes.
Blepharochalasis is characterized by recurrent, non-painful, nonerythematous episodes of eyelid edema. It has been divided into hypertrophic and atrophic forms. In the hypertrophic form recurrent edema results in orbital fat herniation through a weakened orbital septum. Most patients who have blepharochalasis present in an atrophic condition with atrophy of redundant eyelid skin and superior nasal fat pads.
Inflammation of both the eyelids and the conjunctiva.
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Drooping of the upper lid due to deficient development or paralysis of the levator palpebrae muscle.
A focal dystonia that affects the muscles of the eyelids and brow, associated with involuntary recurrent spasm of both eyelids.
A disorder affecting the small intestine. It is caused by the stasis of food and subsequent overgrowth of bacteria in a portion of the small intestine that is unintentionally bypassed as a complication of abdominal surgery or as a sequela of gastrointestinal disorders which impede effective motility. Clinical signs include bloating, abdominal pain, diarrhea and weight loss. If untreated, the clinical course progresses to malabsorption of fats, vitamin B12 and calcium, the latter which predisposes to nephrolithiasis and osteoporosis.
A fluid-filled, raised, often translucent lesion, greater than 1 cm in diameter
A condition in which there is a deviation from or interruption of the normal coagulation properties of the blood.
Endogenous substances, usually proteins, that are involved in the blood coagulation process.
An antigenic mismatch between donor and recipient blood. Antibodies present in the recipient's serum may be directed against antigens in the donor product. Such a mismatch may result in a transfusion reaction in which, for example, donor blood is hemolyzed. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984).
Disorders caused by abnormalities in platelet count or function.
Hematologic diseases caused by structural or functional defects of BLOOD PROTEINS.
Any agent that is able to increase blood volume and/or increase the oxygen transport in the blood.
Bloom syndrome (BSyn) is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an early age. Despite their very small head circumference, most affected individuals have normal intellectual ability. Women may be fertile but often have early menopause, and men tend to be infertile, with only one confirmed case of paternity. Serious medical complications that are more common than in the general population and that also appear at unusually early ages include chronic obstructive pulmonary disease, diabetes mellitus as a result of insulin resistance, and cancer of a wide variety of types and anatomic sites.
A reovirus infection, chiefly of sheep, characterized by a swollen blue tongue, catarrhal inflammation of upper respiratory and gastrointestinal tracts, and often by inflammation of sensitive laminae of the feet and coronet.
Involuntary reddening, especially of the face, associated with feelings of embarrassment, confusion or shame.
Preoccupations with appearance or self-image causing significant distress or impairment in important areas of functioning.
An abnormality of temperature homeostasis.
A clinical manifestation consisting of alterations in an individual's weight from his or her norm.
A benign fluid filled simple cyst of bone filled with serous fluid.
Any disorder of development of the bone.
Diseases of the bones related to hyperfunction or hypofunction of the endocrine glands.
Bone diseases caused by pathogenic microorganisms.
A group of disorders that affect the bones secondary to increased levels of minerals or deficient levels of minerals such as calcium, magnesium, phosphorus, and vitamin D. Representative examples are osteomalacia, osteoporosis, and Paget disease.
Increase in the number of hematopoietic cells in the bone marrow. It may involve all or individual hematopoietic cell lines.
A benign, intermediate, or malignant neoplasm involving the bone or articular cartilage.
An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.
Congenital disorder of lambs caused by a virus closely related to or identical with certain strains of bovine viral diarrhea virus.
Borderline intellectual disability is defined as an intelligence quotient (IQ) in the range of 70-85.
A disorder characterized by an enduring pattern of unstable self-image and mood together with volatile interpersonal relationships, self-damaging impulsivity, recurrent suicidal threats or gestures and/or self-mutilating behavior.
Infections with bacteria of the genus BORDETELLA.
A weakly acidic hydrate of boric oxide with mild antiseptic, antifungal, and antiviral properties. The exact mechanism of action of boric acid is unknown; generally cytotoxic to all cells. It is used in the treatment of yeast infections and cold sores.
An encephalomyelitis of horses, sheep and cattle caused by BORNA DISEASE VIRUS.
Infections with bacteria of the genus BORRELIA.
Antiserum given therapeutically in BOTULISM.
A serotype of botulinum toxins that has specificity for cleavage of SYNAPTOSOMAL-ASSOCIATED PROTEIN 25.
Toxic proteins produced from the species CLOSTRIDIUM BOTULINUM. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon ENDOCYTOSIS into PRESYNAPTIC NERVE ENDINGS. Once inside the cell the botulinum toxin light chain cleaves specific SNARE proteins which are essential for secretion of ACETYLCHOLINE by SYNAPTIC VESICLES. This inhibition of acetylcholine release results in muscular PARALYSIS.
A febrile disease of the Mediterranean area, the Crimea, Africa, and India, caused by infection with RICKETTSIA CONORII.
Acute disease of cattle caused by the bovine viral diarrhea viruses (DIARRHEA VIRUSES, BOVINE VIRAL). Often mouth ulcerations are the only sign but fever, diarrhea, drop in milk yield, and loss of appetite are also seen. Severity of clinical disease varies and is strain dependent. Outbreaks are characterized by low morbidity and high mortality.
A form of squamous cell carcinoma in situ. It is a distinct clinicopathological entity and arises from the skin or the mucocutaneous junction. It affects predominantly white males in their 6-8th decades of life. Exposed and non-exposed skin sites are equally affected. UV damage and ingestion of inorganic arsenic may play a role in the development of the disease. On the skin surface, it presents as a single or multiple erythematous, scaly, keratotic patches or plaques. The clinical entity of erythroplasia of Queyrat is regarded as Bowen disease of the penis and it presents as an asymptomatic, red, circumscribed plaque. Morphologically, Bowen disease is characterized by the presence of hyperkeratosis, parakeratosis, dyskeratosis, and acanthosis. The keratotic squamous cells are atypical and display hyperchromatism and abnormal mitotic figures. The dermoepidermal basement membrane is intact. Complete surgical removal of the lesion may be curative.
A circumscribed collection of purulent exudate in the brain, due to bacterial and other infections. The majority are caused by spread of infected material from a focus of suppuration elsewhere in the body, notably the PARANASAL SINUSES, middle ear (see EAR, MIDDLE); HEART (see also ENDOCARDITIS, BACTERIAL), and LUNG. Penetrating CRANIOCEREBRAL TRAUMA and NEUROSURGICAL PROCEDURES may also be associated with this condition. Clinical manifestations include HEADACHE; SEIZURES; focal neurologic deficits; and alterations of consciousness. (Adams et al., Principles of Neurology, 6th ed, pp712-6)
A condition characterized by long-standing brain dysfunction or damage, usually of three months duration or longer. Potential etiologies include BRAIN INFARCTION; certain NEURODEGENERATIVE DISORDERS; CRANIOCEREBRAL TRAUMA; ANOXIA, BRAIN; ENCEPHALITIS; certain NEUROTOXICITY SYNDROMES; metabolic disorders (see BRAIN DISEASES, METABOLIC); and other conditions.
Irreversible absence of cortical and brain stem functioning.
A non-neoplastic or neoplastic disorder that affects the brain.
Acquired or inborn metabolic diseases that produce brain dysfunction or damage. These include primary (i.e., disorders intrinsic to the brain) and secondary (i.e., extracranial) metabolic conditions that adversely affect cerebral function.
Abnormal accumulation of fluid in the brain.
A benign or malignant neoplasm that arises from or metastasizes to the brain.
An occlusion of a branch of the retinal artery.
A branchial cyst is a remnant of embryonic development resulting from a failure of obliteration of a branchial cleft and consists of a subcutaneous cystic mass. Cysts are located anterior or posterior to the ear or in the submandibular region.
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndrome (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (includes fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The exact cancer risks differ slightly depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant.
A non-neoplastic or neoplastic disorder that affects the breast. Representative examples of non-neoplastic disorders include fibrocystic disease, gynecomastia, and mastitis. Representative examples of neoplastic disorders include fibroadenoma, lobular neoplasia, carcinoma, lymphoma, and sarcoma.
Enlargement of the breast due to increased fluid volume.
A fetal presentation in which the baby descends into the birth canal with hips, buttocks or its foot first during delivery.
A benign, borderline, or malignant transitional cell neoplasm arising from the ovary. It constitutes between 1% and 2% of all ovarian neoplasms. The average age at presentation is about 50 years. Grossly it is usually unilateral, firm and white or yellowish. Microscopically it consists of solid and cystic nests of epithelial cells resembling transitional epithelium surrounded by an abundant stromal component of dense, fibroblastic nature.
An agent that blocks the release of adrenergic transmitters and may have other actions. It was formerly used as an antihypertensive agent, but is now proposed as an anti-arrhythmic.
A fibrinolytic and thrombolytic enzyme from Aspergillus oryzae. EC 3.4.99.-.
One of the BENZODIAZEPINES that is used in the treatment of ANXIETY DISORDERS.
A proteolytic enzyme obtained from the pineapple plant that cleaves sulfhydryl groups. The enzyme is adsorbed intact through the gastrointestinal tract and has demonstrated therapeutic benefit. Bromelain has the ability to modulate cytokines, and has also demonstrated anti-inflammatory activity, immune response activity, and fibrinolytic activity.
A mucolytic agent used in the treatment of respiratory disorders associated with viscid or excessive mucus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p744)
A sedative and mild hypnotic with potentially toxic effects.
A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.
A halogenated thymidine analogue with potential antineoplastic and radiosensitizing activities. Bromodeoxyuridine competes with thymidine for incorporation into DNA, resulting in DNA mutation and the inhibition of cell proliferation. As a radiosensitizer, this agent is associated with the inhibition of repair of radiation-induced DNA double-strand breaks.
Histamine H1 antagonist used in treatment of allergies, rhinitis, and urticaria.
An abnormal communication between the bronchus and another organ or anatomic site.
A spasm (sudden, involuntary constriction) of the bronchioles.
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Inflammation and fibrosis of the bronchioles leading to partial or complete obstruction of these airways.
An acute inflammatory disease of the lower RESPIRATORY TRACT, caused by paramyxoviruses, occurring primarily in infants and young children; the viruses most commonly implicated are PARAINFLUENZA VIRUS TYPE 3; RESPIRATORY SYNCYTIAL VIRUS, HUMAN; and METAPNEUMOVIRUS.
An acute or chronic inflammatory process affecting the bronchi.
Agents that cause an increase in the expansion of a bronchus or bronchial tubes.
A rare congenital cystic lesion of the lungs in the mediastinum.
Acute inflammation of the walls of the terminal bronchioles that spreads into the peribronchial alveoli and alveolar ducts. It results in the creation of foci of consolidation, which are surrounded by normal parenchyma. It affects one or more lobes, and is frequently bilateral and basal. It is usually caused by bacteria (e.g., Staphylococcus, Streptococcus, Haemophilus influenzae). Signs and symptoms include fever, cough with production of brown-red sputum, dyspnea, and chest pain.
A chronic lung disease developed after OXYGEN INHALATION THERAPY or mechanical ventilation (VENTILATION, MECHANICAL) usually occurring in certain premature infants (INFANT, PREMATURE) or newborn infants with respiratory distress syndrome (RESPIRATORY DISTRESS SYNDROME, NEWBORN). Histologically, it is characterized by the unusual abnormalities of the bronchioles, such as METAPLASIA, decrease in alveolar number, and formation of CYSTS.
A developmental anomaly in which a mass of nonfunctioning lung tissue lacks normal connection with the tracheobroncheal tree and receives an anomalous blood supply originating from the descending thoracic or abdominal aorta. The mass may be extralobar, i.e., completely separated from normally connected lung, or intralobar, i.e., partly surrounded by normal lung.
A bacterial vaccine for the prevention of brucellosis in man and animal. Brucella abortus vaccine is used for the immunization of cattle, sheep, and goats.
A gram negative bacterial infection caused by bacteria of the genus Brucella. Humans are infected by ingesting unpasteurized milk or meat from infected animals. Signs and symptoms include fevers, sweating, weakness, headache, muscle pain, arthritis and anemia.
A disorder characterized by grinding and clenching of the teeth.
A benzeneacetamide with anti-inflammatory, analgesic, and antipyretic action. It is administered topically, orally, or rectally.
An ionic compound that resists changes in its pH.
An agent belonging to the biguanide class of antidiabetics with antihyperglycemic activity. Buformin is not metabolized and is excreted in the urine. This agent has been withdrawn from the market due to its elevated risk of lactic acidosis.
A form of anomalous eating behavior characterized by binge eating is followed by self-induced vomiting or other compensatory behavior intended to prevent weight gain (purging, fasting or exercising or a combination of these).
A potent sulfamoylanthranilic acid derivative belonging to the class of loop diuretics. In the brain, bumetanide may prevent seizures in neonates by blocking the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC1), thereby inhibiting chloride uptake thus, decreasing the internal chloride concentration in neurons and may block the excitatory effect of GABA in neonates.
N-Butyl-N-(2-(diethylamino)ethyl)-1-naphthamide. A proposed antiarrhythmic that prolongs myocardial refractory period and stabilizes cell membranes.
A form of heart block in which the electrical stimulation of HEART VENTRICLES is interrupted at either one of the branches of BUNDLE OF HIS thus preventing the simultaneous depolarization of the two ventricles.
A naphthalenone and non-cardioselective adrenergic beta-receptor antagonist with anti-glaucoma activity. Upon administration in the eye, levobunolol blocks beta-adrenergic receptors, thereby causing vasoconstriction. Levobunolol also decreases ciliary's body production of aqueous humor, leading to a decrease in aqueous humor.
Virus diseases caused by the BUNYAVIRIDAE.
An adrenergic-beta-2 antagonist that has been used for cardiac arrhythmia, angina pectoris, hypertension, glaucoma, and as an antithrombotic.
A derivative of the opioid alkaloid THEBAINE that is a more potent and longer lasting analgesic than MORPHINE. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use.
An antagonist of histamine that appears to block both H2 and H3 histamine receptors. It has been used in the treatment of ulcers.
Burkitt lymphoma is a rare, aggressive B-cell lymphoma that accounts for 30 to 50% of lymphomas in children but only 1 to 2% of lymphomas in adults (Harris and Horning, 2006). It results from chromosomal translocations that involve the MYC gene (190080) and either the lambda or the kappa light chain immunoglobulin genes (147220, 147200). Burkitt lymphoma is causally related to the Epstein-Barr virus (EBV), although the pathogenetic mechanisms are not clear.
A condition characterized by a burning or tingling sensation on the lips, tongue, or entire mouth.
An excessive stress reaction to one's occupational or professional environment. It may be characterized by feelings of emotional and physical exhaustion, coupled with a sense of frustration and failure.
A potent synthetic analog of GONADOTROPIN-RELEASING HORMONE with D-serine substitution at residue 6, glycine10 deletion, and other modifications.
An anxiolytic agent and serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the BENZODIAZAPINES, but it has an efficacy comparable to DIAZEPAM.
A synthetic derivative of dimethane-sulfonate with antineoplastic and cytotoxic properties. Although its mechanism of action is not fully understood, busulfan appears to act through the alkylation of DNA. Following systemic absorption of busulfan, carbonium ions are formed, resulting in DNA alkylation and DNA breaks and inhibition of DNA replication and RNA transcription. (NCI04)
A benzocycloheptapyridoisoquinolinol that has been used as an antipsychotic, especially in schizophrenia.
A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain.
A beta-2 selective adrenergic antagonist. It is used primarily in animal and tissue experiments to characterize BETA-2 ANDRENERGIC RECEPTORS.
A white, waxy solid mixture of 2- and 3-Tert-butyl-4-hydroxyanisole with a faint aromatic odor. Butylated Hydroxyanisole is a widely used synthetic antioxidant in foods, cosmetics and pharmaceuticals mainly to preserve fats and oils. Butylated Hydroxyanisole is reasonably anticipated to be a human carcinogen. (NCI05)
A di-tert-butyl PHENOL with antioxidant properties.
An orally available bromide salt form of butylscopolamine, a quaternary ammonium derivative of the alkaloid scopolamine, with anticholinergic property. Upon oral administration, hyoscine butylbromide binds to and blocks muscarinic receptors located on postganglionic parasympathetic nerve endings and on smooth muscle cells. This blocks the activity of acetylcholine (Ach) and causes its antispasmodic effect in the gastrointestinal (GI), urinary, uterine, and biliary tracts. This agent may also facilitate radiologic visualization of the GI tract.
A condition of BRONCHOCONSTRICTION resulting from hypersensitive reaction to inhaled dust during the initial processing of cotton, flax, or hemp in the textile industry. Symptoms include wheezing and tightness in the chest.
A loss of body mass, fatigue, and weakness; it is often associated with chronic disease.
A specific decapeptide obtained from the skin of Hila caerulea, an Australian amphibian. Caerulein is similar in action and composition to CHOLECYSTOKININ. It stimulates gastric, biliary, and pancreatic secretion; and certain smooth muscle. It is used in paralytic ileus and as diagnostic aid in pancreatic malfunction.
A methylxanthine alkaloid found in the seeds, nuts, or leaves of a number of plants native to South America and East Asia that is structurally related to adenosine and acts primarily as an adenosine receptor antagonist with psychotropic and anti-inflammatory activities. Upon ingestion, caffeine binds to adenosine receptors in the central nervous system (CNS), which inhibits adenosine binding. This inhibits the adenosine-mediated downregulation of CNS activity; thus, stimulating the activity of the medullary, vagal, vasomotor, and respiratory centers in the brain. This agent also promotes neurotransmitter release that further stimulates the CNS. The anti-inflammatory effects of caffeine are due the nonselective competitive inhibition of phosphodiesterases (PDEs). Inhibition of PDEs raises the intracellular concentration of cyclic AMP (cAMP), activates protein kinase A, and inhibits leukotriene synthesis, which leads to reduced inflammation and innate immunity.
The major circulating metabolite of VITAMIN D3. It is produced in the LIVER and is the best indicator of the body's vitamin D stores. It is effective in the treatment of RICKETS and OSTEOMALACIA, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing properties.
Deposition of calcium in the tissues. It may be the result of a metabolic disorder or long-standing infection, or it may be associated with the presence of cancer.
A rare syndrome characterized by vascular calcification and skin necrosis. It seen in patients with end stage renal disease.
A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults.
A synthetic physiologically-active analog of vitamin D, specifically the vitamin D3 form. Calcitriol regulates calcium in vivo by promoting absorption in the intestine, reabsorption in the kidneys, and, along with parathyroid hormone, regulation of bone growth. A calcitriol receptor-binding protein appears to exist in the mucosa of human intestine. Calcitriol also induces cell cycle arrest at G0/G1 phase of the cell cycle, cell differentiation, and apoptosis, resulting in inhibition of proliferation of some tumor cell types. This agent may be chemopreventive for colon and prostate cancers. (NCI04)
A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
A class of drugs that act by selective inhibition of calcium influx through cellular membranes.
A crystalline, white substance, soluble in water, Calcium Chloride is the chloride salt of calcium, a bivalent metallic element with many crucial biological roles. Calcium is a major constituent of the skeleton but plays many roles as an intracellular and plasma ion as well. In medicine, calcium chloride is also used as a 10% solution in injection, for calcium replenishment. (NCI04)
Contracted name for a salt of ethylenediaminetetraacetate, an agent used as a chelator of lead and some other heavy metals. C10H12CaN2Na2O8.
A drug used to reduce hemorrhage in diabetic retinopathy.
Calcium fluoride. Occurring in nature as the mineral fluorite or fluorspar. It is the primary source of fluorine and its compounds. Pure calcium fluoride is used as a catalyst in dehydration and dehydrogenation and is used to fluoridate drinking water. (From Merck Index, 11th ed)
The calcium salt form of glucaric acid, a natural substance found in many fruits and vegetables, with potential anti-cancer property. One of the key processes in which the human body eliminates toxic chemicals as well as hormones (such as estrogen) is by attaching glucuronic acid to them in the liver and then excreting the complex in the bile. When beta-glucuronidase breaks the bond, it prolongs the stay of the hormone or toxic chemical in the body. Elevated beta-glucuronidase activity has been implicated to be associated with an increased risk for hormone-dependent cancers like breast, prostate, and colon cancers. Therefore, supplementing calcium glucarate may suppress the developments of hormone-dependent cancers.
The calcium salt of gluconic acid. The compound has a variety of uses, including its use as a calcium replenisher in hypocalcemic states.
A white powder prepared from lime that has many medical and industrial uses. It is in many dental formulations, especially for root canal filling.
Disorders in the processing of calcium in the body: its absorption, transport, storage, and utilization.
The calcium salt of the water-soluble vitamin B5, ubiquitously found in plants and animal tissues with antioxidant property. Pentothenate is a component of coenzyme A (CoA) and a part of the vitamin B2 complex. Vitamin B5 is a growth factor and is essential for various metabolic functions, including the metabolism of carbohydrates, proteins, and fatty acids. This vitamin is also involved in the synthesis of cholesterol, lipids, neurotransmitters, steroid hormones, and hemoglobin.
The calcium salt of phosphoric acid with widely used applications. This agent can be used as a countermeasure for exposure to strontium and radium radionuclides. Upon oral uptake, calcium phosphate competes for and blocks the absorption of radium (Ra-226) and strontium (Sr-90) in the gastrointestinal (GI) tract.
Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements.
An inorganic pyrophosphate which affects calcium metabolism in mammals. Abnormalities in its metabolism occur in some human diseases, notably HYPOPHOSPHATASIA and pseudogout (CHONDROCALCINOSIS).
A calcium salt that is used for a variety of purposes including: building materials, as a desiccant, in dentistry as an impression material, cast, or die, and in medicine for immobilizing casts and as a tablet excipient. It exists in various forms and states of hydration. Plaster of Paris is a mixture of powdered and heat-treated gypsum.
A man-made radioactive actinide with atomic symbol Cf, atomic number 98, and atomic weight 251. Its valence can be +2 or +3. Californium has medical use as a radiation source for radiotherapy.
A 17-alkylated orally active androgenic steroid. Calusterone may alter the metabolism of estradiol and reduce estrogen production. (NCI04)
A nematocide effective against a variety of gastrointestinal parasites in cattle, sheep, and horses.
A bicyclic monoterpene ketone found widely in plants, especially CINNAMOMUM CAMPHORA. It is used topically as a skin antipruritic and as an anti-infective agent.
An alkaloid isolated from the Chinese tree Camptotheca acuminata, with antineoplastic activity. During the S phase of the cell cycle, camptothecin selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. (NCI)
Infections with bacteria of the genus CAMPYLOBACTER.
A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas (adenocarcinomas or squamous cell carcinomas), Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.
Infection with a fungus of the genus CANDIDA. It is usually a superficial infection of the moist areas of the body and is generally caused by CANDIDA ALBICANS. (Dorland, 27th ed)
A clinical syndrome characterized by development, usually in infancy or childhood, of a chronic, often widespread candidiasis of skin, nails, and mucous membranes. It may be secondary to one of the immunodeficiency syndromes, inherited as an autosomal recessive trait, or associated with defects in cell-mediated immunity, endocrine disorders, dental stomatitis, or malignancy.
Candidiasis of the skin manifested as eczema-like lesions of the interdigital spaces, perleche, or chronic paronychia. (Dorland, 27th ed)
A fungal infection of the skin, nails, oral and vaginal mucosal sites caused by species of the genus Candida. It manifests with white discoloration of the tongue and swelling, redness, and tenderness of the nails.
Infection of the mucosal lining of the mouth with the fungus Candida albicans.
A phytocannabinoid derived from Cannabis species, which is devoid of psychoactive activity, with analgesic, anti-inflammatory, antineoplastic and chemopreventive activities. Upon administration, cannabidiol (CBD) exerts its anti-proliferative, anti-angiogenic and pro-apoptotic activity through various mechanisms, which likely do not involve signaling by cannabinoid receptor 1 (CB1), CB2, or vanilloid receptor 1. CBD stimulates endoplasmic reticulum (ER) stress and inhibits AKT/mTOR signaling, thereby activating autophagy and promoting apoptosis. In addition, CBD enhances the generation of reactive oxygen species (ROS), which further enhances apoptosis. This agent also upregulates the expression of intercellular adhesion molecule 1 (ICAM-1) and tissue inhibitor of matrix metalloproteinases-1 (TIMP1) and decreases the expression of inhibitor of DNA binding 1 (ID-1). This inhibits cancer cell invasiveness and metastasis. CBD may also activate the transient receptor potential vanilloid type 2 (TRPV2), which may increase the uptake of various cytotoxic agents in cancer cells. The analgesic effect of CBD is mediated through the binding of this agent to and activation of CB1.
Any compound capable of activating the cannabinoid receptor CB1 and/or CB2. Cannabinoids include phytocannabinoids, endocannabinoids and (semi-)synthetic cannabinoids. They exert a wide variety of biological activities including anti-inflammatory, anti-emetic, anticonvulsant, antiglaucoma, analgesic and neuroprotective effects; while some exert psychoactive effects, including euphoria.
A cannabinoid isolated from the plant Cannabis that is a metabolite of tetrahydrocannabinol (THC), with potential immunosuppressive and anti-inflammatory activities. Cannabinol preferentially binds to the cannabinoid G-protein coupled receptor CB2, which is mainly expressed on a variety of immune cells, such as T-cells, B-cells, macrophages and dendritic cells. Stimulation of CB2 receptors by cannabinol may both trigger apoptosis in these cells and inhibit the production of a variety of cytokines. Cannabinol exerts minimal affinity for CB1 and has a weak effect on the central nervous system.
Physical and psychological dependence on the drug cannabis.
A synthetic pregnadiene compound with anti-aldosterone activity.
A toxic compound, isolated from the Spanish fly or blistering beetle (Lytta (Cantharis) vesicatoria) and other insects. It is a potent and specific inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A). This compound can produce severe skin inflammation, and is extremely toxic if ingested orally.
A psychotic disorder characterized by the patient's belief that acquaintances or closely related persons have been replaced by doubles or imposters.
Reduced resistance to rupture of capikllary blood vessels. Capillary fragility may manifest as a bleeding diathesis with spontaneous ecchymoses (bruises).
A condition characterized by the presence of RHEUMATOID ARTHRITIS associated with a specific form of pneumoconiosis, often in coal miners and asbestos workers.
A chili pepper extract with analgesic properties. Capsaicin is a neuropeptide releasing agent selective for primary sensory peripheral neurons. Used topically, capsaicin aids in controlling peripheral nerve pain. This agent has been used experimentally to manipulate substance P and other tachykinins. In addition, capsaicin may be useful in controlling chemotherapy- and radiotherapy-induced mucositis.
A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.
A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.
A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties.
An aziridinylbenzoquinone-based alkylating agent with potential antineoplastic activity. The alkylating group in carboquone becomes activated upon reduction of quinone to the hydroquinone form. This eventually results in the alkylation and crosslinking of DNA, thereby inhibiting DNA replication followed by an induction of apoptosis. In addition, reactive oxygen species may form during redox cycling which may contribute to this agent's cytotoxic activity.
An agent derived from licorice root. It is used for the treatment of digestive tract ulcers, especially in the stomach. Antidiuretic side effects are frequent, but otherwise the drug is low in toxicity.
A hydrazine derivative of dopa. Carbidopa is a peripheral dopa decarboxylase inhibitor that is used as an adjunct to levodopa administration to prevent peripheral biosynthesis of levodopa to dopamine, thereby reducing peripheral side effects. Carbidopa does not penetrate the blood brain barrier so that levodopa, after it reaches the brain, can be metabolized to dopamine by dopa decarboxylase where it exerts its effect on dopamine receptors.
An imidazole antithyroid agent. Carbimazole is metabolized to METHIMAZOLE, which is responsible for the antithyroid activity.
A compound formed when iodoacetic acid reacts with sulfhydryl groups in proteins. It has been used as an anti-infective nasal spray with mucolytic and expectorant action.
Dysfunctions of CARBOHYDRATE METABOLISM resulting from inborn genetic mutations that are inherited or acquired in utero.
A nonmetalic tetravalent element with symbol C, atomic number 6, and atomic weight 12.
Salts or ions of the theoretical carbonic acid, containing the radical CO2(3-). Carbonates are readily decomposed by acids. The carbonates of the alkali metals are water-soluble; all others are insoluble. (From Grant & Hackh's Chemical Dictionary, 5th ed)
A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES.
A proton ionophore that is commonly used as an uncoupling agent in biochemical studies.
A nonsteroidal abortifacient agent that is effective in both the first and second trimesters of PREGNANCY.
A zinc-dependent enzyme isolated from a strain of the bacterium Pseudomonas. Because glucarpidase rapidly hydrolyzes methotrexate into inactive metabolites, it may be useful as a rescue agent for methotrexate-induced nephrotoxicity. In antibody-directed enzyme prodrug therapy (ADEPT), this agent is conjugated with an antibody that binds to a specific tumor cell type, allowing for glucarpidase-catalyzed activation of a co-administered prodrug at the site of the tumor.
An infection of cutaneous and subcutaneous tissue that consists of a cluster of boils. Commonly, the causative agent is STAPHYLOCOCCUS AUREUS. Carbuncles produce fever, leukocytosis, extreme pain, and prostration.
A first-generation sulfonylurea with hypoglycemic activity. Carbutamide was one of the first sulfonylurea compounds used but was withdrawn from the market due to toxic effects on bone marrow. This agent has a long half-life.
Cardiac manifestation of gastrointestinal CARCINOID TUMOR that metastasizes to the liver. Substances secreted by the tumor cells, including SEROTONIN, promote fibrous plaque formation in ENDOCARDIUM and its underlying layers. These deposits cause distortion of the TRICUSPID VALVE and the PULMONARY VALVE eventually leading to STENOSIS and valve regurgitation.
A slow growing neuroendocrine tumor, composed of uniform, round, or polygonal cells having monotonous, centrally located nuclei and small nucleoli, infrequent mitoses, and no necrosis. The tumor may show a variety of patterns, such as solid, trabecular, and acinar. Electron microscopy shows small secretory granules. Immunohistochemical studies reveal NSE, as well as chromogranin immunoreactivity. Malignant histology (cellular pleomorphism, hyperchromatic nuclei, prominent nucleoli, necrosis, and mitoses) can occasionally be seen. Such cases may have an aggressive clinical course. Gastrointestinal tract and lung are common sites of involvement.
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for ""cancer.""
A transplantable carcinoma of the rat that originally appeared spontaneously in the mammary gland of a pregnant albino rat, and which now resembles a carcinoma in young transplants and a sarcoma in older transplants. (Stedman, 25th ed)
A malignant epithelial neoplasm which is confined to the epithelial layer without evidence of further tissue invasion.
A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.
Primary or metastatic malignant neoplasm involving the endometrium (mucous membrane that lines the endometrial cavity).
A carcinoma that arises from the breast in females. It is the most common malignant tumor that affects females.
A primary or metastatic malignant neoplasm involving the larynx. The majority are carcinomas.
An adenocarcinoma arising from the prostate gland. It is one of the most common malignant tumors afflicting men. The majority of adenocarcinomas arise in the peripheral zone and a minority occurs in the central or the transitional zone of the prostate gland. Grading of prostatic adenocarcinoma predicts disease progression and correlates with survival. Several grading systems have been proposed, of which the Gleason system is the most commonly used. Gleason sums of 2 to 4 represent well-differentiated disease, 5 to 7 moderately differentiated disease and 8 to 10 poorly differentiated disease. Prostatic-specific antigen (PSA) serum test is widely used as a screening test for the early detection of prostatic adenocarcinoma. Treatment options include radical prostatectomy, radiation therapy, androgen ablation and cryotherapy. Watchful waiting or surveillance alone is an option for older patients with low-grade or low-stage disease.
A malignant epithelial neoplasm that arises from the rectum and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas.
A tumor (abnormal growth of tissue) of the skin.
A primary or metastatic malignant neoplasm affecting the thyroid gland.
A malignant skin neoplasm that seldom metastasizes but has potentialities for local invasion and destruction. Clinically it is divided into types: nodular, cicatricial, morphaic, and erythematoid (pagetoid). They develop on hair-bearing skin, most commonly on sun-exposed areas. Approximately 85% are found on the head and neck area and the remaining 15% on the trunk and limbs. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1471)
A basal cell carcinoma which displays squamous differentiation. The neoplastic cells have more abundant cytoplasm with more marked keratinization than typical basal cell carcinomas. It usually has a more aggressive clinical course compared to typical basal cell carcinoma, and it may produce regional or widespread metastases.
A carcinoma derived from epithelium of terminal bronchioles, in which the neoplastic tissue extends along the alveolar walls and grows in small masses within the alveoli. Involvement may be uniformly diffuse and massive, or nodular, or lobular. The neoplastic cells are cuboidal or columnar and form papillary structures. Mucin may be demonstrated in some of the cells and in the material in the alveoli, which also includes denuded cells. Metastases in regional lymph nodes, and in even more distant sites, are known to occur, but are infrequent. (From Stedman, 25th ed)
A lung carcinoma arising from the bronchial epithelium.
A transplantable EPITHELIAL CELL neoplasm of rabbits.
A carcinoma entirely confined to the mammary ducts. It is also known as DCIS. There is no evidence of invasion of the basement membrane. Currently, it is classified into three categories: High-grade DCIS, intermediate-grade DCIS and low-grade DCIS. In this classification the DCIS grade is defined by a combination of nuclear grade, architectural growth pattern and presence of necrosis. The size of the lesion as well as the grade and the clearance margins play a major role in dictating the most appropriate therapy for DCIS.
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.
A carcinoma arising from MERKEL CELLS located in the basal layer of the epidermis and occurring most commonly as a primary neuroendocrine carcinoma of the skin. Merkel cells are tactile cells of neuroectodermal origin and histologically show neurosecretory granules. The skin of the head and neck are a common site of Merkel cell carcinoma, occurring generally in elderly patients. (Holland et al., Cancer Medicine, 3d ed, p1245)
An invasive adenocarcinoma composed of malignant glandular cells which contain intracytoplasmic mucin. Often, the infiltrating glandular structures are associated with mucoid stromal formation. It may arise from the large and small intestine, appendix, stomach, lung, ovary, breast, corpus uteri, cervix, vagina, and salivary gland.
Lung cancer is a disease in which certain cells in the lungs become abnormal and multiply uncontrollably to form a tumor. Lung cancer may not cause signs or symptoms in its early stages. Some people with lung cancer have chest pain, frequent coughing, blood in the mucus, breathing problems, trouble swallowing or speaking, loss of appetite and weight loss, fatigue, or swelling in the face or neck. Additional symptoms can develop if the cancer spreads (metastasizes) into other tissues. Lung cancer occurs most often in adults in their sixties or seventies. Most people who develop lung cancer have a history of long-term tobacco smoking; however, the condition can occur in people who have never smoked.Lung cancer is generally divided into two types, small cell lung cancer and non-small cell lung cancer, based on the size of the affected cells when viewed under a microscope. Non-small cell lung cancer accounts for 85 percent of lung cancer, while small cell lung cancer accounts for the remaining 15 percent.Small cell lung cancer grows quickly and in more than half of cases the cancer has spread beyond the lung by the time the condition is diagnosed. Small cell lung cancer often metastasizes, most commonly to the liver, brain, bones, and adrenal glands (small hormone-producing glands located on top of each kidney). After diagnosis, most people with small cell lung cancer survive for about 1 year; less than seven percent survive 5 years.Non-small cell lung cancer is divided into three main subtypes: adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Adenocarcinoma arises from the cells that line the small air sacs (alveoli) located throughout the lungs. Squamous cell carcinoma arises from squamous cells that line the passages leading from the windpipe (trachea) to the lungs (bronchi). Large cell carcinoma arises from epithelial cells that line the lungs. Large cell carcinoma encompasses non-small cell lung cancers that do not appear to be adenocarcinomas or squamous cell carcinomas. The 5-year survival rate for people with non-small cell lung cancer is usually between 11 and 17 percent; it can be lower or higher depending on the subtype and stage of the cancer.
A malignant epithelial neoplasm characterized by a papillary growth pattern. A papillary carcinoma may be composed of glandular cells (papillary adenocarcinoma), squamous cells (papillary squamous cell carcinoma), or transitional cells (papillary transitional cell carcinoma). Bladder carcinoma is a representative example of papillary transitional cell carcinoma.
Hereditary papillary renal cell carcinoma is characterized by the development of multiple, bilateral papillary renal tumors (Zbar et al., 1995). The transmission pattern is consistent with autosomal dominant inheritance with incomplete penetrance. Papillary renal cell carcinoma is histologically and genetically distinct from 2 other forms of inherited renal carcinoma, von Hippel Lindau disease (193300), caused by mutation in the VHL gene (608537) on chromosome 3, and a form associated with the chromosome translocation t(3;8), as described by Cohen et al. (1979). Bodmer et al. (2002) reviewed the molecular genetics of familial and nonfamilial cases of renal cell carcinoma, including the roles of VHL, MET, and translocations involving chromosomes 1, 3, and X. For background information and a discussion of genetic heterogeneity of nonpapillary renal cell carcinoma, see RCC (144700). See also a hereditary syndrome of predisposition to uterine leiomyomas and papillary renal cell carcinoma (HLRCC; 150800) caused by germline mutation in the FH gene (136850).
An infiltrating adenocarcinoma characterized by the presence of desmoplastic stromal reaction.
A carcinoma arising from squamous epithelial cells. Morphologically, it is characterized by the proliferation of atypical, often pleomorphic squamous cells. Squamous cell carcinomas are graded by the degree of cellular differentiation as well, moderately, or poorly differentiated. Well differentiated carcinomas are usually associated with keratin production and the presence of intercellular bridges between adjacent cells. Representative examples are lung squamous cell carcinoma, skin squamous cell carcinoma, and cervical squamous cell carcinoma.
A malignant neoplasm arising from the transitional epithelium, usually affecting the urinary bladder, ureter, or renal pelvis. It may or may not have a papillary configuration. It is graded 1 to 3 or 4 according to the degree of cellular differentiation and architectural patterns. Grade 1 transitional cell carcinoma is histologically benign but it may recur. Transitional cell carcinomas may also affect the upper respiratory tract and the ovaries.
A malignant tumor composed of a mixture of carcinomatous and sarcomatous elements.
Any compound in which a sugar group is covalently bonded through its anomeric carbon to another group via an O-glycosidic bond or an S-glycosidic bond; glycosides involving the latter are also called thioglycosides. However, substances containing N-glycosidic bonds, where the anomeric carbon is bound to some other group via a nitrogen atom, are called glycosylamines; the term ""N-glycoside"" is considered a misnomer by IUPAC and is discouraged. Furthermore, the sugar group needs to be bonded to a non-sugar for the molecule to qualify as a glycoside, thus excluding the polysaccharides. The sugar group in glycosides is known as the glycone, which can be a single sugar group (monosaccharide) or several sugar groups (oligosaccharide); the non-sugar group is known as the aglycone or genin.
A below normal volume of blood pumped from the right or left ventricle of the heart per unit time.
Acute compression of the heart caused by increased intrapericardial pressure due to the collection of blood or fluid in the pericardium from rupture of the heart, penetrating trauma, or progressive effusion.
A dilated cardiomyopathy which is associated with consumption of large amounts of alcohol over a period of years.
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.It usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.
A form of CARDIAC MUSCLE disease in which the ventricular walls are excessively rigid, impeding ventricular filling. It is marked by reduced diastolic volume of either or both ventricles but normal or nearly normal systolic function. It may be idiopathic or associated with other diseases (ENDOMYOCARDIAL FIBROSIS or AMYLOIDOSIS) causing interstitial fibrosis.
Solutions which, upon administration, will temporarily arrest cardiac activity. They are used in the performance of heart surgery.
An agent that prevents damage to the heart, thereby protecting myocardial function.
Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.
A non-neoplastic or neoplastic disorder affecting the heart or the vessels (arteries, veins and lymph vessels). Representative examples of non-neoplastic cardiovascular disorders are endocarditis and hypertension. Representative examples of neoplastic cardiovascular disorders are endocardial myxoma and angiosarcoma.
Substances that inhibit or arrest DENTAL CARIES formation. (Boucher's Clinical Dental Terminology, 4th ed)
A centrally acting skeletal muscle relaxant whose mechanism of action is not completely understood but may be related to its sedative actions. It is used as an adjunct in the symptomatic treatment of musculoskeletal conditions associated with painful muscle spasm. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1202)
A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
A constituent of STRIATED MUSCLE and LIVER. It is an amino acid derivative and an essential cofactor for fatty acid metabolism.
A dipeptide comprised of a beta-alanine and a 3-methyl-L-histidine, which is found in dietary red meat, with potential antioxidant, metal-chelating and anti-glycation activities. Carnosine scavenges both reactive oxygen species (ROS) and unsaturated aldehydes produced by cell membrane lipid peroxidation. Additionally, this dipeptide may reduce the rate of formation of advanced glycation end-products (AGE). Altogether, this may protect cells against oxidative damage. In addition, carnosine is able to chelate toxic metals.
A class of hydrocarbons (carotenes) and their oxygenated derivatives which exhibit chemopreventive properties. Carotenoids are pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall.
A non-neoplastic or neoplastic disorder affecting the carotid artery.
Blood clot formation in any part of the CAROTID ARTERIES. This may produce CAROTID STENOSIS or occlusion of the vessel, leading to TRANSIENT ISCHEMIC ATTACK; CEREBRAL INFARCTION; or AMAUROSIS FUGAX.
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia adjacent to or in the bifurcation of the common carotid artery. Most patients present with a slow growing, painless mass in the neck.
A narrowing of the carotid artery lumen. It is usually caused by the formation of an atherosclerotic plaque. Symptoms are usually present when there is severe narrowing or obstruction of the arterial lumen and manifest as ischemic cerebrovascular accidents.
Carpal tunnel syndrome is a disorder caused by disturbances in nerve function (neuropathy), leading to pain and numbness or tingling (paresthesia) primarily in the wrist and hand. While carpal tunnel syndrome can occur at any age, it most often affects people between the ages of 40 and 60. In more than half of cases, both hands are affected; however, the severity may vary between hands. When only one hand is affected, it is most often the hand used for writing (the dominant hand).In carpal tunnel syndrome, the pain or paresthesia is usually felt in the wrist, the palm, and the first four fingers of the hand. These signs and symptoms often develop during sleep and are noticeable upon waking. Affected individuals typically shake their hand to get rid of the pain and numbness, a characteristic move known as the flick sign. As the condition advances, the signs and symptoms begin to occur during the day as well. Affected individuals may have difficulty performing manual tasks such as turning doorknobs, fastening buttons, or opening jars. The symptoms of carpal tunnel syndrome may be triggered by certain activities that flex or extend the wrist, such as driving, typing, or holding a telephone.Over time, people with carpal tunnel syndrome can have muscle and nerve wasting (atrophy) in the affected hand and a reduced ability to detect sensations, which can be mistaken for an improvement of symptoms.
A water-soluble extractive mixture of sulfated polysaccharides from RED ALGAE. Chief sources are the Irish moss CHONDRUS CRISPUS (Carrageen), and Gigartina stellata. It is used as a stabilizer, for suspending COCOA in chocolate manufacture, and to clarify BEVERAGES.
An individual who carries an inheritable genetic mutation without manifestation of the associated condition.
A sensation of discomfort associated with ground travel; symptoms may include nausea, vomiting, dizziness or sweating.
A beta-adrenergic antagonist used as an anti-arrhythmia agent, an anti-angina agent, an antihypertensive agent, and an antiglaucoma agent.
The hydrochloride salt form of articaine, an amide-type local anesthetic. Articaine hydrochloride reversibly blocks nerve impulse conduction by binding to specific membrane sodium ion channels thereby interfering with the electrical excitation in the nerve, slowing the propagation of the nerve impulse and reducing the rate of rise of the action potential. This results in a loss of sensation at the injection site. Articaine hydrochloride is used for relief of pain in minor operations, usually in combination with the vasoconstrictor epinephrine.
Pathological processes involving the chondral tissue (CARTILAGE).
A mixture of related phosphoproteins occurring in milk and cheese. The group is characterized as one of the most nutritive milk proteins, containing all of the common amino acids and rich in the essential ones.
A vegetable oil pressed from the seeds of the castor bean, Ricinus communis. Castor oil has many industrial applications and is used medicinally as a laxative and as an excipient.
Diseases of the domestic cat (Felis catus or F. domesticus). This term does not include diseases of the so-called big cats such as CHEETAHS; LIONS; tigers, cougars, panthers, leopards, and other Felidae for which the heading CARNIVORA is used.
A bacterial infection caused by Bartonella henselae. It is transmitted to humans from a scratch, bite, or lick from a cat. A blister or a bump appears on the skin following the scratch or bite. Subsequently, there is lymph node enlargement around the scratch or bite site. The lymph node enlargement most often occurs under the arm or the neck. Some patients experience fever, fatigue, headaches or sore throat as well.
A nervous system disorder characterized by diminished responsiveness and consciousness, and rigidity of the body.
A condition characterized by transient weakness or paralysis of somatic musculature triggered by an emotional stimulus or physical exertion. Cataplexy is frequently associated with NARCOLEPSY. During a cataplectic attack, there is a marked reduction in muscle tone similar to the normal physiologic hypotonia that accompanies rapid eye movement sleep (SLEEP, REM). (From Adams et al., Principles of Neurology, 6th ed, p396)
An acute or prolonged illness usually considered to be life-threatening or with the threat of serious residual disability. Treatment may be radical and is frequently costly.
A neuropsychiatric disorder characterized by one or more of the following essential features: immobility, mutism, negativism (active or passive refusal to follow commands), mannerisms, stereotypies, posturing, grimacing, excitement, echolalia, echopraxia, muscular rigidity, and stupor; sometimes punctuated by sudden violent outbursts, panic, or hallucinations. This condition may be associated with psychiatric illnesses (e.g., SCHIZOPHRENIA; MOOD DISORDERS) or organic disorders (NEUROLEPTIC MALIGNANT SYNDROME; ENCEPHALITIS, etc.). (From DSM-IV, 4th ed, 1994; APA, Thesaurus of Psychological Index Terms, 1994)
An antioxidant flavonoid, occurring especially in woody plants as both (+)-catechin and (-)-epicatechin (cis) forms.
A general class of ortho-dihydroxyphenylalkylamines derived from TYROSINE.
Agents that are used to stimulate evacuation of the bowels.
Diseases of domestic cattle of the genus Bos. It includes diseases of cows, yaks, and zebus.
A rare neurologic disorder caused by impingement of the nerve roots of the cauda equina secondary to disc herniation, spinal stenosis, vertebral fracture, neoplasm or infection. Clinical signs may include bladder or bowel dysfunction, paresthesia and weakness of the lower extremities. The development of neurogenic bladder implies that surgical decompression was either ineffective, delayed or not attempted.
A complex regional pain syndrome characterized by burning pain and marked sensitivity to touch (HYPERESTHESIA) in the distribution of an injured peripheral nerve. Autonomic dysfunction in the form of sudomotor (i.e., sympathetic innervation to sweat glands), vasomotor, and trophic skin changes may also occur. (Adams et al., Principles of Neurology, 6th ed, p1359)
Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint.
A benign or malignant neoplasm that affects the cecum. Representative examples of benign neoplasms include lipoma and leiomyoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma. Cecal adenomas always exhibit epithelial dysplasia and are considered premalignant neoplasms.
Celiac disease is a systemic autoimmune disease that can be associated with gastrointestinal findings (diarrhea, malabsorption, abdominal pain and distension, bloating, vomiting, and weight loss) and/or highly variable non-gastrointestinal findings (dermatitis herpetiformis, chronic fatigue, joint pain/inflammation, iron deficiency anemia, migraines, depression, attention-deficit disorder, epilepsy, osteoporosis/osteopenia, infertility and/or recurrent fetal loss, vitamin deficiencies, short stature, failure to thrive, delayed puberty, dental enamel defects, and autoimmune disorders). Classic celiac disease, characterized by mild to severe gastrointestinal symptoms, is less common than non-classic celiac disease, characterized by absence of gastrointestinal symptoms.
A pathologic process that involves the transformation of normal cells to a neoplastic state and resulting in polyclonal or monoclonal neoplastic cell proliferation.
An endocellulase with specificity for the hydrolysis of 1,4-beta-glucosidic linkages in CELLULOSE, lichenin, and cereal beta-glucans.
A bacterial infection and inflammation of the skin und subcutaneous tissues. []
A rare benign bone-forming neoplasm usually arising from the jaw. It is a well-circumscribed lytic tumor that varies in size. The cell of origin is the cementoblast.
A non-steroidal anti-fertility agent with anti-hormonal properties.
A class of drugs producing both physiological and psychological effects through a variety of mechanisms. They can be divided into ""specific"" agents, e.g., affecting an identifiable molecular mechanism unique to target cells bearing receptors for that agent, and ""nonspecific"" agents, those producing effects on different target cells and acting by diverse molecular mechanisms. Those with nonspecific mechanisms are generally further classed according to whether they produce behavioral depression or stimulation. Those with specific mechanisms are classed by locus of action or specific therapeutic use. (From Gilman AG, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p252)
A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents).
A structural abnormality of the central nervous system.
An infectious process that affects the brain and/or spinal cord. Representative examples include encephalitis, poliomyelitis, arachnoiditis, and meningitis.
Clouding of the middle area of the cornea, usually as a result of scarring due to Infection, injury, or inflammation.
Blockage of blood flow in the central retinal artery.
An ester of DIMETHYLAMINOETHANOL and para-chlorophenoxyacetic acid.
A subperiosteal hemorrhage limited to the surface of one cranial bone, a usually benign condition seen in the newborn as a result of bone trauma.
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, GAIT ATAXIA, and MUSCLE HYPOTONIA.
A condition marked by progressive CEREBELLAR ATAXIA combined with MYOCLONUS usually presenting in the third decade of life or later. Additional clinical features may include generalized and focal SEIZURES, spasticity, and DYSKINESIAS. Autosomal recessive and autosomal dominant patterns of inheritance have been reported. Pathologically, the dentate nucleus and brachium conjunctivum of the CEREBELLUM are atrophic, with variable involvement of the spinal cord, cerebellar cortex, and basal ganglia. (From Joynt, Clinical Neurology, 1991, Ch37, pp60-1)
A benign or malignant (primary or metastatic) tumor involving the cerebellum. -- 2003
A congenital or acquired aneurysm within the cranium.
Vascular diseases characterized by thickening and hardening of the walls of ARTERIES inside the SKULL. There are three subtypes: (1) atherosclerosis with fatty deposits in the ARTERIAL INTIMA; (2) Monckeberg's sclerosis with calcium deposits in the media and (3) arteriolosclerosis involving the small caliber arteries. Clinical signs include HEADACHE; CONFUSION; transient blindness (AMAUROSIS FUGAX); speech impairment; and HEMIPARESIS.
Cerebral arteriovenous malformation (AVM) is a congenital malformative communication between the veins and the arteries in the brain in the form of a nidus, an anatomical structure composed of dilated and tangled supplying arterioles and drainage veins with no intervening capillary bed, that can be asymptomatic or cause, depending on the location and the size of the AVM, headaches of varying severity, generalized or focal seizures, focalneurological defects (weakness, numbness, speech difficulties, vision loss) or potentially fatal intracranial hemorrhage in case the AVM ruptures.
Pathological conditions of intracranial ARTERIES supplying the CEREBRUM. These diseases often are due to abnormalities or pathological processes in the ANTERIOR CEREBRAL ARTERY; MIDDLE CEREBRAL ARTERY; and POSTERIOR CEREBRAL ARTERY.
Atherosclerosis of the cerebral vasculature.
Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures.
An ischemic condition of the brain, producing a persistent focal neurological deficit in the area of distribution of the cerebral arteries.
Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.
A brief attack (from a few minutes to an hour) of cerebral dysfunction of vascular origin, with no persistent neurological deficit.
A group of disorders affecting the development of movement and posture, often accompanied by disturbances of sensation, perception, cognition, and behavior. It results from damage to the fetal or infant brain.
A rare central nervous system demyelinating condition affecting children and young adults. Pathologic findings include a large, sharply defined, asymmetric focus of myelin destruction that may involve an entire lobe or cerebral hemisphere. The clinical course tends to be progressive and includes dementia, cortical blindness, cortical deafness, spastic hemiplegia, and pseudobulbar palsy. Concentric sclerosis of Balo is differentiated from diffuse cerebral sclerosis of Schilder by the pathologic finding of alternating bands of destruction and preservation of myelin in concentric rings. Alpers' Syndrome refers to a heterogeneous group of diseases that feature progressive cerebral deterioration and liver disease. (From Adams et al., Principles of Neurology, 6th ed, p914; Dev Neurosci 1991;13(4-5):267-73)
A neoplasm that involves a brain ventricle. It may be a primary neoplasm arising from a brain ventricle, a metastasis from a distant anatomic site, or an extension of an invasive neoplasm from an adjacent brain structure.
Neutral glycosphingolipids that contain a monosaccharide, normally glucose or galactose, in 1-ortho-beta-glycosidic linkage with the primary alcohol of an N-acyl sphingoid (ceramide). In plants the monosaccharide is normally glucose and the sphingoid usually phytosphingosine. In animals, the monosaccharide is usually galactose, though this may vary with the tissue and the sphingoid is usually sphingosine or dihydrosphingosine. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1st ed)
Discharge of cerebrospinal fluid through the ear structures.
Discharge of cerebrospinal fluid through the nose.
A disorder resulting from inadequate blood flow in the vessels that supply the brain. Representative examples include cerebrovascular ischemia, cerebral embolism, and cerebral infarction.
An element of the rare earth family of metals. It has the atomic symbol Ce, atomic number 58, and atomic weight 140.12. Cerium is a malleable metal used in industrial applications.
An epoxydodecadienamide isolated from several species, including ACREMONIUM, Acrocylindrum, and Helicoceras. It inhibits the biosynthesis of several lipids by interfering with enzyme function.
A primary or metastatic malignant neoplasm involving the cervix.
Abnormal growth of tissue projecting from a mucous membrane of the endocervix.
Thoracic outlet syndrome, either nerve or vessel compression, due to a cervical rib
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the neck.
An acute or chronic inflammatory process that affects the cervix. Causes include sexually transmitted diseases and bacterial infections. Clinical manifestations include abnormal vaginal bleeding and vaginal discharge.
A distinct type of headache characterized by piercing, throbbing, or electric-shock-like chronic pain in the upper neck, back of the head, and behind the ears, usually on one side.
A non-neoplastic or neoplastic disorder that affects the cervix. Representative examples include cervicitis, endocervical polyp, and carcinoma.
Abnormal development of immature squamous EPITHELIAL CELLS of the UTERINE CERVIX, a term used to describe premalignant cytological changes in the cervical EPITHELIUM. These atypical cells do not penetrate the epithelial BASEMENT MEMBRANE.
Eversion of the endocervix with protrusion of the central (endocervical) columnar epithelium through the external os of the cervis into the vaginal milieu.
A cervix that shows a painless dilation and shortening during the second trimester of pregnancy with resultant recurrent pregnancy loss or delivery is considered incompetent
A benign or malignant neoplasm that affects the cervix. Representative examples include endocervical polyp, rhabdomyoma, carcinoma, and melanoma.
Infections with true tapeworms of the helminth subclass CESTODA.
Non-ionic surfactant of the polyethylene glycol family. It is used as a solubilizer and emulsifying agent in foods, cosmetics, and pharmaceuticals, often as an ointment base, and also as a research tool.
Cetyltrimethylammonium compounds that have cationic detergent, antiseptic, and disinfectant activities. They are used in pharmaceuticals, foods, and cosmetics as preservatives; on skin, mucous membranes, etc., as antiseptics or cleansers, and also as emulsifiers. These compounds are toxic when used orally due to neuromuscular blockade.
Cationic bactericidal surfactant used as a topical antiseptic for skin, wounds, mucous membranes, instruments, etc.; and also as a component in mouthwash and lozenges.
A dilated cardiomyopathy caused by the protozoan Trypanosoma cruzi. Patients may present with heart block, congestive heart failure, or anginal symptoms.
A chronic epithelioid cell granulomatous inflammation of the meibomian gland caused by inflammation of a blocked meibomian gland. A chalazion or meibomian cyst appears as a painless tuberous swelling in the upper lid without loss of eyelashes.
The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection.
Acute, localized autoinoculable infectious disease usually acquired through sexual contact. Caused by HAEMOPHILUS DUCREYI, it occurs endemically almost worldwide, especially in tropical and subtropical countries and more commonly in seaports and urban areas than in rural areas.
An amorphous form of carbon prepared from the incomplete combustion of animal or vegetable matter, e.g., wood. The activated form of charcoal is used in the treatment of poisoning. (Grant & Hackh's Chemical Dictionary, 5th ed)
Charcot-Marie-Tooth disease encompasses a group of disorders called hereditary sensory and motor neuropathies that damage the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves that worsens over time can result in alteration or loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity and age of onset even among members of the same family. Some people never realize they have the disorder because their symptoms are so mild, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in very rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy.Typically, the earliest symptoms of Charcot-Marie-Tooth disease result from muscle atrophy in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (steppage gait) and increase the risk of ankle injuries and tripping. As the disease worsens, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair.Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with Charcot-Marie-Tooth disease typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In rare cases, affected individuals have loss of vision or gradual hearing loss that sometimes leads to deafness.There are several types of Charcot-Marie-Tooth disease, which are differentiated by their effects on nerve cells and patterns of inheritance. Type 1 (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to transmit nerve impulses. These abnormalities slow the transmission of nerve impulses and can affect the health of the nerve fiber. Type 2 (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body to muscles or to sense organs. These abnormalities reduce the strength of the nerve impulse. In forms of Charcot-Marie-Tooth disease classified as intermediate type, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both myelin and axons. Type 4 (CMT4) is distinguished from the other types by its pattern of inheritance; it can affect either the axons or the myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in genes on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) indicate different genetic causes.Sometimes other, historical names are used to refer to particular forms of Charcot-Marie-Tooth disease. For example, Roussy-Levy syndrome is a form of CMT11 with the additional feature of rhythmic shaking (tremors). Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called type 3 (CMT3). Depending on the specific gene that is altered, this severe, early-onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome.
Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism, immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, or hemophagocytic lymphohistiocytosis, a life-threatening, hyperinflammatory condition. All affected individuals including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) develop neurologic findings during early adulthood.
An inflammatory process affecting the lip.
Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.
Used for biological phenomena, diseases, syndromes, congenital abnormalities, or symptoms caused by endogenous or exogenous substances.
A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.
Cherubism is a childhood-onset, autoinflammatory bone disease characterized by bilateral and symmetric proliferative fibroosseous lesions limited to the mandible and maxilla. The enlargement is usually symmetric in nature. The phenotype ranges from no clinical manifestations to severe mandibular and maxillary overgrowth with respiratory, vision, speech, and swallowing problems. In most affected persons, teeth are displaced, unerupted, unformed, or absent, or may appear to be floating in cystlike spaces; malocclusion, premature exfoliation of deciduous teeth, and root resorption have also been reported. The course and duration of the active process of bone destruction varies between affected individuals; the onset is usually in early childhood, and typically new lesions can occur until puberty. Regression of the lesions occurs as they become filled with bone and remodel during the second and third decade of life. By age 30 years, the facial abnormalities associated with cherubism are not usually recognizable and residual deformity of the jaws is rare. Typically, cherubism is an isolated benign condition; the affected person has normal intellectual skills and is without other physical anomalies.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the chest.
Painful sensation in the chest wall region.
An abnormal pattern of breathing characterized by alternating periods of apnea and deep, rapid breathing. The cycle begins with slow, shallow breaths that gradually increase in depth and rate and is then followed by a period of apnea. The period of apnea can last 5 to 30 seconds, then the cycle repeats every 45 seconds to 3 minutes.
A POSTPARTUM condition consists of persistent lactation (GALACTORRHEA) and AMENORRHEA in patients not BREAST FEEDING.
A contagious childhood disorder caused by the varicella zoster virus. It is transmitted via respiratory secretions and contact with chickenpox blister contents. It presents with a vesicular skin rash, usually associated with fever, headache, and myalgias. The pruritic fluid-filled vesicles occur 10-21 days after exposure and last for 3-4 days. An additional 3-4 days of malaise follows before the affected individual feels better. An individual is contagious 1-2 days prior to the appearance of the blisters until all blisters are crusted over. Generally, healthy individuals recover without complications.
An acute infection caused by a mosquito-borne alphavirus CHIKUNGUNYA VIRUS characterized by RASH; FEVER; JOINT PAINS; CONJUNCTIVITIS; MENINGOENCEPHALITIS; LYMPHOPENIA; and THROMBOCYTOPENIA.
A rare condition characterized by skin inflammation, blister formation, swelling and ulcerations in the extremities. It occurs in persons exposed to cold temperatures.
Abuse of children in a family, institutional, or other setting. (APA, Thesaurus of Psychological Index Terms, 1994)
Sexual maltreatment of the child or minor.
Disturbances considered to be pathological based on age and stage appropriateness, e.g., conduct disturbances and anaclitic depression. This concept does not include psychoneuroses, psychoses, or personality disorders with fixed patterns.
A disorder diagnosed in childhood that is marked by either physical or mental impairment or both, which in turn affects the child from achieving age related developmental milestones.
Severe distortions in the development of many basic psychological functions that are not normal for any stage in development. These distortions are manifested in sustained social impairment, speech abnormalities, and peculiar motor movements.
Disorders caused by nutritional imbalance, either overnutrition or undernutrition, occurring in children ages 2 to 12 years.
Reactions to an event or set of events which are considered to be of pathological degree, that have not developed into a neurosis, psychosis, or personality disorder with fixed patterns.
An infection that is caused by Chlamydia trachomatis.
Infections with bacteria of the family CHLAMYDIACEAE.
A hypnotic and sedative used in the treatment of INSOMNIA.
A derivative of CHLORAL HYDRATE that was used as a sedative but has been replaced by safer and more effective drugs. Its most common use is as a general anesthetic in animal experiments.
A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed)
A long-acting benzodiazepine with anxiolytic, sedative and hypnotic activity. Chlordiazepoxide exerts its effect by binding to the benzodiazepine site at the gamma-aminobutyric acid (GABA) receptor-chloride ionophore complex in the central nervous system (CNS). This leads to an increase in the opening of chloride channels, membrane hyperpolarization and increases the inhibitory effect of GABA on the CNS.
A biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, chlorhexidine penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram positive bacteria are more negatively charged, they are more sensitive to this agent.
A nicotinic antagonist used primarily as a ganglionic blocker in animal research. It has been used as an antihypertensive agent but has been supplanted by more specific drugs in most clinical applications.
An orally active synthetic progestational hormone used often in combinations as an oral contraceptive.
A mercurial compound that has been used as a diuretic but is now superseded by more potent and less toxic drugs. The radiolabeled form has been used as a diagnostic and research tool.
A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors.
A non-benzodiazepine that is used in the management of anxiety. It has been suggested for use in the treatment of muscle spasm.
A colorless to white crystalline compound with a camphoraceous odor and taste. It is a widely used preservative in various pharmaceutical solutions, especially injectables. Also, it is an active ingredient in certain oral sedatives and topical anesthetics.
A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.
A cytotoxic sulfhydryl reagent that inhibits several subcellular metabolic systems and is used as a tool in cellular physiology.
A 4-aminoquinoline with antimalarial, anti-inflammatory, and potential chemosensitization and radiosensitization activities. Although the mechanism is not well understood, chloroquine is shown to inhibit the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. This agent may also interfere with the biosynthesis of nucleic acids. Chloroquine's potential chemosensitizing and radiosensitizing activities in cancer may be related to its inhibition of autophagy, a cellular mechanism involving lysosomal degradation that minimizes the production of reactive oxygen species (ROS) related to tumor reoxygenation and tumor exposure to chemotherapeutic agents and radiation.
8-Hydroxyquinolinols chlorinated on the number 5 and/or 7 carbon atom(s). They are antibacterial, antiprotozoal, and antidiarrheal, especially in amebiasis, and have also been used as antiseborrheics. The compounds are mostly used topically, but have been used also as animal feed additives. They may cause optic and other neuropathies and are most frequently administered in combination with other agents.
A short-acting, benzothiadiazinesulfonamide derivative and prototypical thiazide diuretic. Chlorothiazide is excreted unchanged by the kidneys.
A powerful synthetic, non-steroidal estrogen.
A centrally acting muscle relaxant. Its mode of action is unknown. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1203)
A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than PROMETHAZINE.
A chlorinated analogue of phentermine, a sympathomimetic amine with central nervous system (CNS) stimulating and anorexic activity. Chlorphentermine acts by facilitating the release of catecholamines, especially noradrenaline and dopamine, from nerve terminals in the brain and also inhibits their uptake. The increase in synaptic concentrations of these catecholamines causes behavioral changes including an increase in motor activity, mental alertness and excitement, causes euphoria, and suppresses appetite.
A phenothiazine and traditional antipsychotic agent with anti-emetic activity. Chlorpromazine exerts its antipsychotic effect by blocking postsynaptic dopamine receptors in cortical and limbic areas of the brain, thereby preventing the excess of dopamine in the brain. This leads to a reduction in psychotic symptoms, such as hallucinations and delusions. Chlorpromazine appears to exert its anti-emetic activity by blocking the dopamine receptors in the chemical trigger zone (CTZ) in the brain, thereby relieving nausea and vomiting.
A long-acting, first-generation sulfonylurea with hypoglycemic activity. Compared to other sulfonylureas, chlorpropamide has an increased risk of prolonged hypoglycemia because of its long half-life.
A thioxanthine with effects similar to the phenothiazine antipsychotics.
Local anti-infective agent used for skin, gastrointestinal, and vaginal infections with fungi, protozoa, and certain bacteria. In animals, it causes central nervous system damage and is not administered parenterally. It is also used as antiseptic, fungistat, or deodorant.
A benzenesulfonamide-phthalimidine that tautomerizes to a BENZOPHENONES form. It is considered a thiazide-like diuretic.
A benzoxazolone derivative with mild sedative and centrally-acting muscle relaxant activities. Although its exact mechanism of action is unknown, chlorzoxazone (CZ) appears to act at the spinal cord and subcortical levels of the brain to inhibit multisynaptic reflex arcs involved in producing and maintaining muscle spasms. This agent is extensively hydroxylated by cytochrome P450 2E1 (CYP2E1) to 6-hydroxychlorzoxazone (HCZ),11,12 which is subsequently glucuronidated and eliminated renally. Highly selective for CYP2E1, CZ may be used as a selective probe for phenotyping CYP2E1 in humans; the ratio of HCZ-to-CZ plasma concentrations obtained 2 to 4 hours after oral administration of CZ may be used as a phenotypic measure of CYP2E1 enzymatic activity.
A congenital abnormality that is characterized by a blocked CHOANAE, the opening between the nose and the NASOPHARYNX. Blockage can be unilateral or bilateral; bony or membranous.
A benign exophytic growth that arises from the nasopharynx.
Interference with respiration by compression or obstruction of the larynx or trachea.
Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic).
A benign, well-demarcated polypoid neoplasm arising from the bile duct epithelium. According to the growth pattern, it is classified as tubular, papillary, or tubulopapillary. Adenomas arising from the extrahepatic bile ducts usually produce symptoms related to biliary obstruction.
An acute or chronic inflammatory process affecting the biliary tract.
An autoimmune inflammatory disorder characterized by destruction of the small intrahepatic bile ducts. It affects predominantly females and it may lead to cirrhosis and liver failure. Patients have antimitochondrial and antinuclear antibodies in the peripheral blood.
Cholangitis associated with evident ductal fibrosis that develops as a consequence of long-standing bile duct inflammatory, obstruction, or ischemic injury; it can be obliterative or nonobliterative.
A steroid hormone produced in the skin when exposed to ultraviolet light or obtained from dietary sources. The active form of cholecalciferol, 1,25-dihydroxycholecalciferol (calcitriol) plays an important role in maintaining blood calcium and phosphorus levels and mineralization of bone. The activated form of cholecalciferol binds to vitamin D receptors and modulates gene expression. This leads to an increase in serum calcium concentrations by increasing intestinal absorption of phosphorus and calcium, promoting distal renal tubular reabsorption of calcium and increasing osteoclastic resorption.
The presence of inflammatory changes in the gallbladder. [HPO:probinson]
A peptide, of about 33 amino acids, secreted by the upper INTESTINAL MUCOSA and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety.
A congenital anatomic malformation of a bile duct, including cystic dilatation of the extrahepatic bile duct or the large intrahepatic bile duct. Classification is based on the site and type of dilatation. Type I is most common.
Hard, pebble-like deposits that form within the gallbladder.
An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is VIBRIO CHOLERAE. This condition can lead to severe dehydration in a matter of hours unless quickly treated.
Vaccines or candidate vaccines used to prevent infection with VIBRIO CHOLERAE. The original cholera vaccine consisted of killed bacteria, but other kinds of vaccines now exist.
gastrointestinal agent that stimulates the flow of bile into the duodenum or stimulates the production of bile by the liver.
Impairment of bile flow due to obstruction in bile ducts.
Impairment of bile flow due to injury to the HEPATOCYTES; BILE CANALICULI; or the intrahepatic bile ducts (BILE DUCTS, INTRAHEPATIC).
A non-neoplastic mass of keratin-producing squamous EPITHELIUM, frequently occurring in the MENINGES; bones of the skull, and most commonly in the MIDDLE EAR and MASTOID region. Cholesteatoma can be congenital or acquired. Cholesteatoma is not a tumor nor is it associated with high CHOLESTEROL.
An autosomal recessive disorder caused by mutations in the gene for acid lipase (STEROL ESTERASE). It is characterized by the accumulation of neutral lipids, particularly CHOLESTEROL ESTERS in leukocytes, fibroblasts, and hepatocytes.
A strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium Cl(-) anion.
The 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholanic acid family of bile acids in man, usually conjugated with glycine or taurine. They act as detergents to solubilize fats for intestinal absorption, are reabsorbed by the small intestine, and are used as cholagogues and choleretics.
A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.
A condition produced by a deficiency of CHOLINE in animals. Choline is known as a lipotropic agent because it has been shown to promote the transport of excess fat from the liver under certain conditions in laboratory animals. Combined deficiency of choline (included in the B vitamin complex) and all other methyl group donors causes liver cirrhosis in some animals. Unlike compounds normally considered as vitamins, choline does not serve as a cofactor in enzymatic reactions. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984)
Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.
Drugs used to reverse the inactivation of cholinesterase caused by organophosphates or sulfonates. They are an important component of therapy in agricultural, industrial, and military poisonings by organophosphates and sulfonates.
A benign, chondroid-producing, well-circumscribed, lytic neoplasm usually arising from the epiphysis of long bones. It is characterized by the presence of chondroblasts, osteoclast-like giant cells, chondroid formation, calcification, and mitotic activity. In aggressive cases, there is rearrangement of the 8q21 chromosome band. It occurs most frequently in children and young adults and rarely metastasizes.
A heterogeneous group of bone dysplasias, the common character of which is stippling of the epiphyses in infancy. The group includes a severe autosomal recessive form (CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC), an autosomal dominant form (Conradi-Hunermann syndrome), and a milder X-linked form. Metabolic defects associated with impaired peroxisomes are present only in the rhizomelic form.
Any dysfunction in the growth of cartilage.
A mucopolysaccharide constituent of chondrin. (Grant & Hackh's Chemical Dictionary, 5th ed)
Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.
A degeneration of the ARTICULAR CARTILAGE of the PATELLA, caused by a decrease in sulfated MUCOPOLYSACCHARIDES in the ground substance. When accompanied by pain, it is sometimes considered part of or confused with PATELLOFEMORAL PAIN SYNDROME.
An uncommon, benign cartilaginous neoplasm usually occurring in adults. The nodular tumor arises from the synovial membranes of joints. It is characterized by the presence of chondrocytes, nuclear pleomorphism, and hyaline cartilage differentiation. Clinical presentation may include joint pain, swelling, and limited range of motion.
A malignant cartilaginous matrix-producing mesenchymal neoplasm arising from the bone and soft tissue. It usually affects middle-aged to elderly adults. The pelvic bones, ribs, shoulder girdle, and long bones are the most common sites of involvement. Most chondrosarcomas arise de novo, but some may develop in a preexisting benign cartilaginous lesion.
Chordomas are rare, clinically malignant tumors derived from notochordal remnants. They occur along the length of the spinal axis, predominantly in the sphenooccipital, vertebral, and sacrococcygeal regions. They are characterized by slow growth, local destruction of bone, extension into adjacent soft tissues, and, rarely, distant metastatic spread (Stepanek et al., 1998). The incidence of chordoma is age-dependent, with fewer than 5% occurring in children and adolescents (summary by McMaster et al., 2011).
A neurological condition affecting the involuntary movements. It is characterized by brief, non-repetitive irregular muscle contractions. It is seen in patients with Huntington's disease.
A complete hydatidiform mole or very rarely a partial mole that invades the myometrium.
A morphologic finding indicating inflammation of the fetal sac membranes. It is characterized by neutrophilic infiltration of the amnion and chorion.
A malignant metastatic form of trophoblastic tumors. Unlike the HYDATIDIFORM MOLE, choriocarcinoma contains no CHORIONIC VILLI but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (TROPHOBLASTS). It is characterized by the large amounts of CHORIONIC GONADOTROPIN produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin (CHORIOCARCINOMA, NON-GESTATIONAL).
Fibrous connective tissue resulting from incomplete healing of a wound (i.e., a scar) located in the choroid and retina or the eye.
An inflammation of the choroid and retina.
A mass of histologically normal tissue present in an abnormal location.
Any structural abnormality of the choroid.
Hemorrhage from the vessels of the choroid.
A benign or malignant neoplasm that affects the choroid.
Choroideremia (CHM) is characterized by progressive chorioretinal degeneration in affected males and milder signs in carrier females. Typically, symptoms in affected males evolve from night blindness to peripheral visual field loss, with central vision preserved until late in life. Although carrier females are generally asymptomatic, signs of chorioretinal degeneration can be observed with careful fundus examination. These signs become more readily apparent after the second decade.
Hemophilia B is characterized by deficiency in factor IX clotting activity that results in prolonged oozing after injuries, tooth extractions, or surgery, and delayed or recurrent bleeding prior to complete wound healing. The age of diagnosis and frequency of bleeding episodes are related to the level of factor IX clotting activity. In individuals with severe hemophilia B, spontaneous joint or deep-muscle bleeding is the most frequent sign. Individuals with severe hemophilia B are usually diagnosed during the first two years of life; without prophylactic treatment, they may average up to two to five spontaneous bleeding episodes each month. Individuals with moderate hemophilia B seldom have spontaneous bleeding; however, they do have prolonged or delayed oozing after relatively minor trauma and are usually diagnosed before age five to six years; the frequency of bleeding episodes varies from once a month to once a year. Individuals with mild hemophilia B do not have spontaneous bleeding episodes; however, without pre- and postoperative treatment, abnormal bleeding occurs with surgery or tooth extractions; the frequency of bleeding may vary from once a year to once every ten years. Individuals with mild hemophilia B are often not diagnosed until later in life. In any individual with hemophilia B, bleeding episodes may be more frequent in childhood and adolescence than in adulthood. Approximately 30% of heterozygous females have factor IX clotting activity lower than 40% and are at risk for bleeding (even if the affected family member has mild hemophilia B), although symptoms are usually mild. After major trauma or invasive procedures, prolonged or excessive bleeding usually occurs, regardless of severity.
Scaly papule or warty growth, caused by five fungi, that spreads as a result of satellite lesions affecting the foot or leg. The extremity may become swollen and, at its distal portion, covered with various nodular, tumorous, verrucous lesions that resemble cauliflower. In rare instances, the disease may begin on the hand or wrist and involve the entire upper extremity. (Arnold, Odom, and James, Andrew's Diseases of the Skin, 8th ed, p362)
A glycosidic antineoplastic antibiotic isolated from the bacterium Streptomyces griseus. Chromomycin antibiotics bind to the minor groove of DNA, specifically to guanine/cytosine base pairs, and inhibit RNA synthesis.
An irregularity in the number or structure of chromosomes, usually in the form of a gain (duplication), loss (deletion), exchange (translocation), or alteration in sequence (inversion) of genetic material.
A disorder that results from a chromosomal abnormality.
Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.
A subcategory of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis.
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)
Chronic inflammatory disorder of the lungs characterized by the presence of eosinophils in the interalveolar septa and alveolar spaces and peripheral blood eosinophilia. Chest x-rays reveal peripheral infiltrates. Approximately half of the patients have history of asthma or atopic disease. Signs and symptoms include fever, dyspnea, cough, and weight loss. Following treatment with corticosteroids, the eosinophilic infiltrates in the lungs disappear, resulting in dramatic clinical improvement.
Inflammation of the ethmoid sinus that typically lasts beyond eight weeks. It is caused by infections, allergies, and the presence of sinus polyps or a deviated septum. Signs and symptoms include headache, nasal discharge, swelling in the face, dizziness, and breathing difficulties.
Inflammation of the frontal sinus that typically lasts beyond eight weeks. It is caused by infections, allergies, and the presence of sinus polyps or a deviated septum. Signs and symptoms include headache, nasal discharge, swelling in the face, dizziness, and breathing difficulties.
Chronic painless inflammation of the gums. It is characterized by erythema and edema of the gums and bleeding while brushing the teeth.
A slowly progressive inflammation of the glomeruli characterized by immune complex deposits on the epithelial side of the glomerular basement membrane.
Inflammation of the maxillary sinus that typically lasts beyond eight weeks. It is caused by infections, allergies, and the presence of sinus polyps or a deviated septum. Signs and symptoms include headache, nasal discharge, swelling in the face, dizziness, and breathing difficulties.
A neurological disorder presenting in childhood that is characterized by either motor or phonic tics, but not both, that occur daily or nearly daily for at least a year and are not attributed to an identifiable cause.
Chronic inflammation of the nasal cavity mucosa. It may lead to post-nasal drip resulting in chronic sore throat and chronic cough.
Inflammation of the sphenoid sinus that typically lasts beyond eight weeks. It is caused by infections, allergies, and the presence of sinus polyps or a deviated septum. Signs and symptoms include headache, nasal discharge, swelling in the face, dizziness, and breathing difficulties.
An extract of Goa powder; a complex mixture of reduction products of chrysophanic acid, emodin, and emodin monomethyl ether; used locally in ringworm, psoriasis, and eczema.
An autoimmune necrotizing vasculitis with the formation of granulomas. It is a pulmonary and systemic vasculitis associated with eosinophilia.
Accumulation of chyle (milky fluid) in the peritoneal cavity. It results from the disruption of the lymphatic vessels in the abdominal cavity.
A milky pleural effusion resulting from accumulation of lymph fluid in the pleural cavity. Causes include malignancies (usually lymphoma), trauma to the thoracic duct, tuberculosis, sarcoidosis, and congenital causes.
A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6.
A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.
The formation of fibrous tissue in the place of normal tissue during the process of WOUND HEALING. It includes scar tissue formation occurring in healing internal organs as well as in the skin after surface injuries.
A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, IMIPENEM, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukotriene E4.
Primary ciliary dyskinesia (PCD) is associated with situs abnormalities, abnormal sperm motility, and abnormal ciliary structure and function that result in retention of mucus and bacteria in the respiratory tract leading to chronic otosinopulmonary disease. More than 75% of full-term neonates with PCD have ""neonatal respiratory distress"" requiring supplemental oxygen for days to weeks. Chronic airway infection, apparent in early childhood, results in bronchiectasis that is almost uniformly present in adulthood. Nasal congestion and sinus infections, apparent in early childhood, persist through adulthood. Chronic/recurrent ear infection, apparent in most young children, can be associated with transient or later irreversible hearing loss. Situs inversus totalis (mirror-image reversal of all visceral organs with no apparent physiologic consequences) is present in 40%-50% of individuals with PCD; heterotaxy (discordance of right and left patterns of ordinarily asymmetric structures that can be associated with significant malformations) is present in approximately 12%. Virtually all males with PCD are infertile as a result of abnormal sperm motility.
A histamine H(2)-receptor antagonist. Enhancing anti-tumor cell-mediated responses, cimetidine blocks histamine's ability to stimulate suppressor T lymphocyte activity and to inhibit natural killer (NK) cell activity and interleukin-2 production. Cimetidine also may inhibit tumor growth by suppressing histamine's growth-factor activity and blocking histamine-induced stimulation of vascular endothelial growth factor (VEGF), a pro-angiogenic growth factor. (NCI04)
A serotonin antagonist with limited antihistaminic, anticholinergic, and immunosuppressive activity.
Alkaloids extracted from various species of Cinchona.
Derivatives of cinnamic acid (the structural formula: phenyl-HC=CH-COO-), including its salts and esters.
A piperazine derivative having histamine H1-receptor and calcium-channel blocking activity with vasodilating and antiemetic properties but it induces PARKINSONIAN DISORDERS.
Synthetic antimicrobial related to OXOLINIC ACID and NALIDIXIC ACID and used in URINARY TRACT INFECTIONS.
A broad-spectrum antimicrobial carboxyfluoroquinoline.
An alkylating-like inorganic platinum agent (cis-diamminedichloroplatinum) with antineoplastic activity. Cisplatin forms highly reactive, charged, platinum complexes which bind to nucleophilic groups such as GC-rich sites in DNA inducing intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links. These cross-links result in apoptosis and cell growth inhibition.
A bicyclic phthalene derivative and selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activities. Citalopram selectively inhibits the neuronal reuptake of the neurotransmitter serotonin (5-HT) in presynaptic cells in the central nervous system, thereby increasing levels of 5-HT within the synaptic cleft and enhancing the actions of serotonin on its receptors. Increased serotonergic neurotransmission results in antidepressive and anxiolytic effects.
The hydrochloride salt form of prilocaine, an intermediate-acting local anesthetic of the amide type chemically related to lidocaine. Prilocaine hydrochloride binds to voltage-gated sodium ion channels in the neuronal membrane, thereby preventing the permeability of sodium ions. This leads to a stabilization of the neuronal membrane and inhibits depolarization and results in a reversible blockage of nerve impulse generation and propagation along nerve fibres and subsequent reversible loss of sensation.
A series of oxidative reactions in the breakdown of acetyl units derived from GLUCOSE; FATTY ACIDS; or AMINO ACIDS by means of tricarboxylic acid intermediates. The end products are CARBON DIOXIDE, water, and energy in the form of phosphate bonds.
A non-essential amino acid. In hepatocytes, L-citrulline is synthesized in the urea cycle by the addition of carbon dioxide and ammonia to ornithine. L-citrulline is converted into L-arginine by the enzymes argininosuccinate synthetase and argininosuccinate lyase in the presence of L-aspartate and ATP. Subsequently, L-arginine is converted to nitric oxide by nitric oxide synthase and L-citrulline is regenerated as a by-product.
An abnormal fear of being in a closed or narrow space with no escape.
A gap in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
A congenital abnormality consisting of a fissure in the midline of the hard and/or soft palate; it is the result of the failure of the two sides of the palate to fuse during embryonic development.
Cleidocranial dysplasia (CCD) spectrum disorder is a skeletal dysplasia that represents a clinical continuum ranging from classic CCD (triad of delayed closure of the cranial sutures, hypoplastic or aplastic clavicles, and dental abnormalities) to mild CCD to isolated dental anomalies without the skeletal features. Most individuals come to diagnosis because they have classic features. At birth, affected individuals typically have abnormally large, wide-open fontanels that may remain open throughout life. Clavicular hypoplasia can result in narrow, sloping shoulders that can be opposed at the midline. Moderate short stature may be observed, with most affected individuals being shorter than their unaffected sibs. Dental anomalies may include supernumerary teeth, eruption failure of the permanent teeth, and presence of the second permanent molar with the primary dentition. Individuals with CCD spectrum disorder are at increased risk of developing recurrent sinus infections, recurrent ear infections leading to conductive hearing loss, and upper-airway obstruction. Intelligence is typically normal.
A histamine H1 antagonist used as the hydrogen fumarate in hay fever, rhinitis, allergic skin conditions, and pruritus. It causes drowsiness.
A substituted phenylaminoethanol and a long-acting beta-2 adrenergic agonist with sympathomimetic activity. Clenbuterol selectively binds to and activates beta-2 adrenergic receptors in bronchiolar smooth muscle, thereby causing stimulation of adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased intracellular cAMP levels cause relaxation of smooth muscle. In addition, clenbuterol also stimulates central nervous system (CNS), and causes an increase in blood pressure and heart rate due to both beta-2 and beta-1 adrenergic activities. This agent may also exert an anabolic or anti-catabolic effect due to as of yet unidentified mechanisms.
A derivative of PREDNISOLONE with high glucocorticoid activity and low mineralocorticoid activity. Absorbed through the skin faster than FLUOCINONIDE, it is used topically in treatment of PSORIASIS but may cause marked adrenocortical suppression.
The disodium salt of a nitrogen-free bisphosphonate analog of naturally occurring pyrophosphate. Clodronate binds to calcium and inhibits osteoclastic bone resorption and hydroxyapatite crystal formation and dissolution, resulting in a reduction of bone turnover. This agent may control malignancy-associated hypercalcemia, inhibit osteolytic bone metastasis and decrease pain.
A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619)
An oral hypolipemic agent primarily used in DOGS and RATS.
A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)
An antilipemic agent that is the biologically active metabolite of CLOFIBRATE.
A triphenyl ethylene stilbene derivative which is an estrogen agonist or antagonist depending on the target tissue. Note that ENCLOMIPHENE and ZUCLOMIPHENE are the (E) and (Z) isomers of Clomiphene respectively.
A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.
A synthetic benzodiazepine derivative used for myotonic or atonic seizures, absence seizures, and photosensitive epilepsy, anticonvulsant Clonazepam appears to enhance gamma-aminobutyric acid receptor responses, although its mechanism of action is not clearly understood. It is seldom effective in generalized tonic-clonic or partial seizures. (NCI04)
An imidazoline derivate and centrally-acting alpha-adrenergic agonist, with antihypertensive activity. Clonidine binds to and stimulates central alpha-2 adrenergic receptors, thereby reducing the amount of norepinephrine (NE) release and thus decreasing sympathetic outflow to the heart, kidneys, and peripheral vasculature. The reduction in sympathetic outflow leads to decreased peripheral vascular resistance, decreased blood pressure, and decreased heart rate. In addition, clonidine binds to imidazoline receptor subtype 1 (I1), which may also contribute to a reduction in blood pressure.
Infection of the biliary passages with CLONORCHIS SINENSIS, also called Opisthorchis sinensis. It may lead to inflammation of the biliary tract, proliferation of biliary epithelium, progressive portal fibrosis, and sometimes bile duct carcinoma. Extension to the liver may lead to fatty changes and cirrhosis. (From Dorland, 27th ed)
A form of involuntary muscular movement characterized by alternating contractions and relaxation in rapid succession. In the context of reflex testing, the ability to elicit clonus indicates injury to the nerve tracts above the point at which the reflex was initiated.
A piperidine and sulfamoylbenzamide-based diuretic with thiazide-like diuretic activity. Clopamide appears to work in a similar manner as the thiazide diuretics and has a similar potency as chlorothiazide and hydrochlorothiazide.
A thioxanthene with therapeutic actions similar to the phenothiazine antipsychotics. It is an antagonist at D1 and D2 dopamine receptors.
A very effective anticoccidial agent used in poultry.
A synthetic prostaglandin F2alpha analog. The compound has luteolytic effects and is used for the synchronization of estrus in cattle.
A benzodiazepine with anxiolytic, sedative, hypnotic, and anticonvulsant properties. Clorazepate dipotassium exerts its effect by de-activating the nervous system through potentiation of the inhibitory effect of gamma-aminobutyric acid (GABA) on the GABA-A receptors by binding to a site that is distinct from the GABA binding site. Its inhibitory effect is caused by an increase in GABA-mediated chloride channel opening events, leading to hyperpolarization and synaptic inhibition.
An antidepressive agent and monoamine oxidase inhibitor related to PARGYLINE.
A metalloproteinase which degrades helical regions of native collagen to small fragments. Preferred cleavage is -Gly in the sequence -Pro-Xaa-Gly-Pro-. Six forms (or 2 classes) have been isolated from Clostridium histolyticum that are immunologically cross-reactive but possess different sequences and different specificities. Other variants have been isolated from Bacillus cereus, Empedobacter collagenolyticum, Pseudomonas marinoglutinosa, and species of Vibrio and Streptomyces. EC 3.4.24.3.
Infections with bacteria of the genus CLOSTRIDIUM.
A synthetic, imidazole derivate with broad-spectrum, antifungal activity. Clotrimazole inhibits biosynthesis of sterols, particularly ergosterol, an essential component of the fungal cell membrane, thereby damaging and affecting the permeability of the cell membrane. This results in leakage and loss of essential intracellular compounds, and eventually causes cell lysis.
A transplantable melanoma that arose spontaneously in a mouse of DBA strain, and which grows and metastasizes in mice of related strains. (dictionarybarn.com)
A synthetic dibenzo-diazepine derivative, atypical antipsychotic Clozapine blocks several neurotransmitter receptors in the brain (dopamine type 4, serotonin type 2, norepinephrine, acetylcholine, and histamine receptors). Unlike traditional antipsychotic agents, it weakly blocks dopamine type 2 receptors. It relieves schizophrenic symptoms (hallucinations, delusions, dementia). (NCI04)
An abnormal enlargement of the terminal phalanges accompanied by increased length-wise curvature of the nails, giving the digits a club-like appearance. Clubbing has been noted with a wide variety of conditions, including pulmonary and cardiac diseases, liver disorders, and disorders of the gastrointestinal tract.
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
A headache disorder that is characterized by periodic severe, unilateral orbital, supraorbital, and/or temporal pain, and is associated with ipsilateral cranial autonomic symptoms.
A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) (Merck Index, 11th ed).
biologically active form of vitamin B12, in which the cyanide counterion has been replaced by an adenine nucleoside.
The combination of two or more different factors in the production of cancer.
A fungal infection caused by Coccidioides immitis. Affected individuals usually have mild flu-like symptoms. However, pneumonia and systemic involvement with the formation of abscesses may develop as complications of the disease.
A parasitic infection caused by Coccidia. It affects livestock, birds and humans. In humans the parasite infests the intestinal tract and may cause watery diarrhea, abdominal pain, fever, nausea and vomiting.
Agents useful in the treatment or prevention of COCCIDIOSIS in man or animals.
Pathological processes of the snail-like structure (COCHLEA) of the inner ear (LABYRINTH) which can involve its nervous tissue, blood vessels, or fluid (ENDOLYMPH).
Cockayne syndrome (referred to as CS in this GeneReview) spans a phenotypic spectrum that includes: CS type I, the ""classic"" or ""moderate"" form; CS type II, a more severe form with symptoms present at birth; this form overlaps with cerebrooculofacioskeletal syndrome (COFS) or Pena-Shokeir syndrome type II; CS type III, a milder form; Xeroderma pigmentosum-Cockayne syndrome (XP-CS). CS type I (moderate CS) is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade. CS type II (severe CS or early-onset CS) is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age seven years. CS type III (mild CS or late-onset CS) is characterized by essentially normal growth and cognitive development or by late onset. Xeroderma pigmentosum-Cockayne syndrome (XP-CS) includes facial freckling and early skin cancers typical of XP and some features typical of CS, including intellectual disability, spasticity, short stature, and hypogonadism. XP-CS does not include skeletal involvement, the facial phenotype of CS, or CNS dysmyelination and calcifications.
Oil obtained from fresh livers of the cod family, Gadidae. It is a source of VITAMIN A and VITAMIN D.
A naturally occurring phenanthrene alkaloid and opioid agonist with analgesic, antidiarrheal and antitussive activities. Codeine mimics the actions of endogenous opioids by binding to the opioid receptors at many sites within the central nervous system (CNS). Stimulation of mu-subtype opioid receptors results in a decrease in the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline; in addition, the codeine metabolite morphine induces opening of G-protein-coupled inwardly rectifying potassium (GIRK) channels and blocks the opening of N-type voltage-gated calcium channels, resulting in hyperpolarization and reduced neuronal excitability. Stimulation of gut mu-subtype opioid receptors results in a reduction in intestinal motility and delayed intestinal transit times. Antitussive activity is mediated through codeine's action on the cough center in the medulla.
The phosphate salt of codeine, a naturally occurring phenanthrene alkaloid and opioid agonist with analgesic, antidiarrheal and antitussive activities. Codeine mimics the actions of endogenous opioids by binding to the opioid receptors at many sites within the central nervous system (CNS). Stimulation of mu-subtype opioid receptors results in a decrease in the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline; in addition, the codeine metabolite morphine induces opening of G-protein-coupled inwardly rectifying potassium (GIRK) channels and blocks the opening of N-type voltage-gated calcium channels, resulting in hyperpolarization and reduced neuronal excitability. Stimulation of gut mu-subtype opioid receptors results in a reduction in intestinal motility and delayed intestinal transit times. Antitussive activity is mediated through codeine's action on the cough center in the medulla.
a rare infection caused by larvae of the dog tapeworm
A ribonucleoside antibiotic synergist and adenosine deaminase inhibitor isolated from Nocardia interforma and Streptomyces kaniharaensis. It is proposed as an antineoplastic synergist and immunosuppressant.
A category of psychiatric disorders which are characterized by a deficit in cognition or memory.
A lung lesion that appears as a round coin-shaped shadow in the chest radiographs.
A birth control method adopted during sexual intercourse by withdrawing the penis from the vagina before ejaculation.
A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE).
A positively charged, non-digestible, triamine and epoxypropane copolymer anion-exchange resin that binds to bile acids in the intestine to form an insoluble complex, which is excreted in the feces.
Colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine (colon, cecum and rectum). Colitides may be acute and self-limited or chronic, and broadly fit into the category of digestive diseases.
A chronic inflammatory bowel disease that includes characteristic ulcers, or open sores, in the colon. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset and intermittent periods of exacerbated symptoms contrasting with periods that are relatively symptom-free. In contrast to Crohn's disease this special form of colitis begins in the distal parts of the rectum, spreads continually upwards and affects only mucose and submucose tissue of the colon.
A family of large fibrous proteins that are the main components of connective tissue and are responsible for maintaining tissue structure.
Historically, a heterogeneous group of acute and chronic diseases, including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, dermatomyositis, etc. This classification was based on the notion that ""collagen"" was equivalent to ""connective tissue"", but with the present recognition of the different types of collagen and the aggregates derived from them as distinct entities, the term ""collagen diseases"" now pertains exclusively to those inherited conditions in which the primary defect is at the gene level and affects collagen biosynthesis, post-translational modification, or extracellular processing directly. (From Cecil Textbook of Medicine, 19th ed, p1494)
A liquid dose form consisting of active substance(s) in a mixture of ether and ethanol.
A suspension of metallic gold particles.
Coloboma is an ocular birth defect resulting from abnormal development of the eye during embryogenesis. It is defined as a congenital defect in any ocular tissue, typically presenting as absent tissue or a gap, at a site consistent with aberrant closure of the optic fissure. Failure of fusion can lead to coloboma of one or multiple regions of the inferior portion of the eye affecting any part of the globe traversed by the fissure, from the iris to the optic nerve, including the ciliary body, retina, and choroid. Coloboma is also frequently associated with small (microphthalmic) or absent (anophthalmic) eyes as part of an interrelated spectrum of developmental eye anomalies, and can affect either one or both eyes (summary by Kelberman et al., 2014). Genetic Heterogeneity of Ocular Coloboma A recessive form of ocular coloboma (216820) is caused by mutation in the SALL2 gene (602219) on chromosome 14q11.
Pathological processes in the COLON region of the large intestine (INTESTINE, LARGE).
Chronic or recurrent colonic disorders without an identifiable structural or biochemical explanation. The widely recognized IRRITABLE BOWEL SYNDROME falls into this category.
A benign or malignant neoplasm that affects the colon. Representative examples of benign neoplasms include lipoma and leiomyoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma. Colonic adenomas always exhibit epithelial dysplasia and are considered premalignant neoplasms.
A polypoid lesion that arises from the colon and protrudes into the lumen. This group includes adenomatous polyps, serrated polyps, and hamartomatous polyps.
Functional obstruction of the COLON leading to MEGACOLON in the absence of obvious COLONIC DISEASES or mechanical obstruction. When this condition is acquired, acute, and coexisting with another medical condition (trauma, surgery, serious injuries or illness, or medication), it is called Ogilvie's syndrome.
An anomaly in the ability to discriminate between or recognize colors.
A febrile illness characterized by chills, aches, vomiting, leukopenia, and sometimes encephalitis. It is caused by the COLORADO TICK FEVER VIRUS, a reovirus transmitted by the tick Dermacentor andersoni.
A malignant epithelial neoplasm that arises from the colon or rectum and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas.
A benign or malignant neoplasm that affects the colon or rectum. Representative examples of benign neoplasms include lipoma and leiomyoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma. Colorectal adenomas always exhibit epithelial dysplasia and are considered premalignant neoplasms.
A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.
A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.
Neurotic reactions to unusual, severe, or overwhelming military stress.
Characterized by the fusiform or saccular dilatation of the COMMON BILE DUCT.
Diseases of the COMMON BILE DUCT including the AMPULLA OF VATER and the SPHINCTER OF ODDI.
Tumor or cancer of the COMMON BILE DUCT including the AMPULLA OF VATER and the SPHINCTER OF ODDI.
A catarrhal disorder of the upper respiratory tract, which may be viral or a mixed infection. It generally involves a runny nose, nasal congestion, and sneezing.
Heterogeneous group of immunodeficiency syndromes characterized by hypogammaglobulinemia of most isotypes, variable B-cell defects, and the presence of recurrent bacterial infections.
A disorder resulting from the presence and activity of a microbial, viral, fungal, or parasitic agent. It can be transmitted by direct or indirect contact.
A form of hydrocephalus in which there is no visible obstruction to the flow of the cerebrospinal fluid between the ventricles and subarachnoid space.
A disorder characterized by an individual's inability to comprehend or share ideas or feelings because of an impairment in language, speech, or hearing.
The coexistence of two or more disease processes.
Conditions in which increased pressure within a limited space compromises the BLOOD CIRCULATION and function of tissue within that space. Some of the causes of increased pressure are TRAUMA, tight dressings, HEMORRHAGE, and exercise. Sequelae include nerve compression (NERVE COMPRESSION SYNDROMES); PARALYSIS; and ISCHEMIC CONTRACTURE.
Serum proteins that inhibit, antagonize, or inactivate COMPLEMENT C1 or its subunits.
Any physiologic process in which a protease directs the cleavage of complement components C4, C2, or factor B which then form the C3 and C5 convertases for the classical and lectin pathways, respectively. This process is involved in direct lysis of target cells, immune adherence and phagocytosis of pathogens, and recruitment and activation of immunocompetent cells.
Complement activation initiated by the interaction of microbial ANTIGENS with COMPLEMENT C3B. When COMPLEMENT FACTOR B binds to the membrane-bound C3b, COMPLEMENT FACTOR D cleaves it to form alternative C3 CONVERTASE (C3BBB) which, stabilized by COMPLEMENT FACTOR P, is able to cleave multiple COMPLEMENT C3 to form alternative C5 CONVERTASE (C3BBB3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Complement activation initiated by the binding of COMPLEMENT C1 to ANTIGEN-ANTIBODY COMPLEXES at the COMPLEMENT C1Q subunit. This leads to the sequential activation of COMPLEMENT C1R and COMPLEMENT C1S subunits. Activated C1s cleaves COMPLEMENT C4 and COMPLEMENT C2 forming the membrane-bound classical C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and the assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Any disease or disorder that occurs during the course of, or because of, another disease, treatment, or procedure.
A disease or disorder that is associated with a transplanted organ.
A disorder characterized by an enduring pattern of inflexibility, extreme orderliness, and perfectionism which interfere with efficiency and which may manifest in many different contexts, including work and leisure activities, financial matters, and issues of morality or ethics.
A sexually transmitted papillary growth caused by the human papillomavirus. It usually arises in the skin and mucous membranes of the perianal region and external genitalia.
A mental state characterized by a lack of clear and orderly thought and behavior.
A congenital abnormality in which the meninges protrude through a defect in the cranium.
Congenital hepatic fibrosis (CHF) is a developmental disorder of the portobiliary system characterized histologically by defective remodeling of the ductal plate (ductal plate malformation; DPM), abnormal branching of the intrahepatic portal veins, and progressive fibrosis of the portal tracts. CHF may or may not be associated with macroscopic cystic dilatation of the intrahepatic bile ducts. Clinical findings include enlarged, abnormally shaped liver, relatively well-preserved hepatocellular function, and portal hypertension (PH) resulting in splenomegaly, hypersplenism, and gastroesophageal varices. Pulmonary hypertension (portopulmonary hypertension) and vascular shunts in the pulmonary parenchyma (hepatopulmonary syndrome), complications of PH, can also be seen rarely. Most frequently CHF is associated with ciliopathies (disorders of the primary cilia) that have associated renal disease, the so-called hepatorenal fibrocystic diseases (FCDs). Although the hepatorenal FCDs are currently classified by phenotype, it is likely that gene-based classification will be quite different in the future because of the tremendous genetic and phenotypic overlap between these disorders.
A congenital abnormality in which the meninges protrude through a defect in the spinal column.
A hemorrhage occurring in the conjunctiva of the eye.
A benign or malignant neoplasm that affects the conjunctiva. Representative examples include papilloma, squamous cell carcinoma, and melanoma.
A highly contagious disease characterized by subconjunctival hemorrhage, sudden swelling of the eyelids and congestion, redness, and pain in the eye. Epidemic conjunctivitis caused by Enterovirus 70 (EV-70) was first described in Africa in 1969. It is caused also by Coxsackievirus A24 variant (CA24v). Epidemics by this organism have appeared most frequently in Asia.
Inflammation of the conjunctiva caused by a variety of bacterial agents.
Conjunctivitis that is associated with contact lens wear, and which is characterized by giant papillae in the tarsal conjunctiva.
An infection of the eyes characterized by the presence in conjunctival epithelial cells of inclusion bodies indistinguishable from those of trachoma. It is acquired by infants during birth and by adults from swimming pools. The etiological agent is CHLAMYDIA TRACHOMATIS whose natural habitat appears to be the genito-urinary tract. Inclusion conjunctivitis is a less severe disease than trachoma and usually clears up spontaneously.
Inflammation of the cornea that is seasonal in nature.
Conjunctivitis resulting from viral infection.
A type of primary hyperaldosteronism resulting from a benign neoplasm of the adrenal gland. The adrenal neoplasm increases production of aldosterone. Excess aldosterone causes the kidneys to retain more salt than usual resulting in increases in body fluid levels and blood pressure. The disease is caused by mutations in one of several genes. The most commonly mutated gene is KCNJ5, accounting for an estimated 40 percent of the neoplasms, followed by the CACNA1D and ATP1A1 genes. Changes in other genes cause a small percentage of cases with additional unidentified genes involved in the condition. The disease is generally not inherited but may arise from a mutation occurring after conception.
A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.
Organic mental disorders in which there is impairment of the ability to maintain awareness of self and environment and to respond to environmental stimuli. Dysfunction of the cerebral hemispheres or brain stem RETICULAR FORMATION may result in this condition.
Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.
A group of symptoms that affect an individual's general well being. Representative examples include fever, chills, fatigue, weakness, and weight loss.
Chemical substances that prevent or reduce the probability of CONCEPTION.
Chemical substances or agents with contraceptive activity in females. Use for female contraceptive agents in general or for which there is no specific heading.
Chemical substances or agents with contraceptive activity in males. Use for male contraceptive agents in general or for which there is no specific heading.
An agent taken orally to prevent conception.
Orally administered synthetic sex hormones with contraceptive activity. The oral contraceptive preparation contains a combination of an estrogen, such as ethinyl estradiol, and a progestagen, such as levonorgestrel or norethidrone. The oral contraceptive prevents pregnancy by preventing ovulation and by inducing endometrial and cervical changes undesirable for fertilization and implantation.
Oral contraceptives which owe their effectiveness to hormonal preparations.
Drugs administered orally and sequentially for contraceptive purposes.
Oral contraceptives which owe their effectiveness to synthetic preparations.
Contraceptive substances to be used after COITUS. These agents include high doses of estrogenic drugs; progesterone-receptor blockers; ANTIMETABOLITES; ALKALOIDS, and PROSTAGLANDINS.
Postcoital contraceptives which owe their effectiveness to hormonal preparations.
Postcoital contraceptives which owe their effectiveness to synthetic preparations.
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Permanent shortening of a joint, usually resulting from prolonged spasticity in a muscle area.
The period of recovery following an illness.
A disorder whose predominant feature is a loss or alteration in physical functioning that suggests a physical disorder but that is actually a direct expression of a psychological conflict or need.
A seizure occurring in infants and young children that occurs in the setting of fever.
A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.
The orally bioavailable copper salt of D-gluconic acid. In addition to its roles as an enzyme cofactor for cytochrome C oxidase and superoxide dismutase, copper forms complexes with the thiocarbamate disulfiram (DSF) forming DSF-copper complexes, which enhances the DSF-mediated inhibition of the 26S proteasome; proteasome inhibition may result in inhibition of cellular protein degradation, cessation of cell cycle progression, inhibition of cellular proliferation, and the induction of apoptosis in susceptible tumor cell populations.
A malformation of the heart in which the embryonic common PULMONARY VEIN was not incorporated into the LEFT ATRIUM leaving behind a perforated fibromuscular membrane bisecting the left atrium, a three-atrium heart. The opening between the two left atrium sections determines the degree of obstruction to pulmonary venous return, pulmonary venous and pulmonary arterial hypertension.
Toxic glycolipids composed of trehalose dimycolate derivatives. They are produced by MYCOBACTERIUM TUBERCULOSIS and other species of MYCOBACTERIUM. They induce cellular dysfunction in animals.
A non-neoplastic or neoplastic disorder that affects the cornea. Representative examples include keratitis, bullous keratopathy, and squamous cell carcinoma.
A family of inherited disorders characterized by the gradual, progressive accumulation of extraneous material on one or both corneas, which, without proper treatment, can impair vision.
An abnormality of the cornea that is characterized by opacity of one or parts of the cornea.
An excessive amount of fluid in the cornea due to damage of the epithelium or endothelium causing decreased visual acuity.
Area of epithelial tissue loss from corneal surface; associated with inflammatory cells in the cornea and anterior chamber.
Abnormal balloon- or sac-like dilatation in the wall of CORONARY VESSELS. Most coronary aneurysms are due to CORONARY ATHEROSCLEROSIS, and the rest are due to inflammatory diseases, such as KAWASAKI DISEASE.
Atherosclerosis of the coronary vasculature.
An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels.
Coagulation of blood in any of the CORONARY VESSELS. The presence of a blood clot (THROMBUS) often leads to MYOCARDIAL INFARCTION.
A brief and sudden narrowing of a coronary artery.
Malformations of CORONARY VESSELS, either arteries or veins. Included are anomalous origins of coronary arteries; ARTERIOVENOUS FISTULA; CORONARY ANEURYSM; MYOCARDIAL BRIDGING; and others.
A benign ovarian cyst that develops when fluid accumulates in a corpus luteum that failed to regress.
A corticosteroid intermediate in the steroidogenic pathway that converts pregnenolone to aldosterone. In humans, corticosterone has limited glucocorticoid or mineralocorticoid activity.
A peptide of about 41 amino acids that stimulates the release of ADRENOCORTICOTROPIC HORMONE. CRH is synthesized by neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, CRH stimulates the release of ACTH from the PITUITARY GLAND. CRH can also be synthesized in other tissues, such as PLACENTA; ADRENAL MEDULLA; and TESTIS.
A corticosteroid with potent glucocorticoid activity. Therapeutic cortisone is the inactive precursor molecule of the active hormone cortisol, which is the hydroxylation product of cortisone by 11-beta-steroid dehydrogenase. Cortisol increases blood pressure and blood sugar levels, and suppresses the immune system, therefore cortisone is used to treat allergies or inflammation.
Infections with bacteria of the genus CORYNEBACTERIUM.
The N-glucuronide conjugate of cotinine is a major urinary metabolite of NICOTINE. It thus serves as a biomarker of exposure to tobacco SMOKING. It has CNS stimulating properties.
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
A organothiophosphorus cholinesterase inhibitor that is used as an anthelmintic, insecticide, and as a nematocide.
O hydroxycinnamic acid. Pleasant smelling compound found in many plants and released on wilting. Has anticoagulant activity by competing with Vitamin K.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
A daidzein derivative occurring naturally in forage crops which has some estrogenic activity.
A mild, eruptive skin disease of milk cows caused by COWPOX VIRUS, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal.
A heterogeneous group of infections produced by coxsackieviruses, including HERPANGINA, aseptic meningitis (MENINGITIS, ASEPTIC), a common-cold-like syndrome, a non-paralytic poliomyelitis-like syndrome, epidemic pleurodynia (PLEURODYNIA, EPIDEMIC) and a serious MYOCARDITIS.
Incomplete fracture of any part of a tooth, characterized by pain during mastication and sensitivity to heat, cold, sweet or sour tastes, and alcohol; it is often undiagnosed because the tooth is usually X-ray negative and normal to pulp vitality tests.
An involuntary contraction of a muscle in an extremity.
A neoplastic or non-neoplastic disorder that affects one of the cranial nerves.
Abnormal growth of the cells that comprise the cranial nerves.
Crouzon syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.Many features of Crouzon syndrome result from the premature fusion of the skull bones. Abnormal growth of these bones leads to wide-set, bulging eyes and vision problems caused by shallow eye sockets; eyes that do not point in the same direction (strabismus); a beaked nose; and an underdeveloped upper jaw. In addition, people with Crouzon syndrome may have dental problems and hearing loss, which is sometimes accompanied by narrow ear canals. A few people with Crouzon syndrome have an opening in the lip and the roof of the mouth (cleft lip and palate). The severity of these signs and symptoms varies among affected people. People with Crouzon syndrome are usually of normal intelligence.
A benign pituitary-region neoplasm that originates from Rathke's pouch. Craniopharyngiomas are benign slow growing tumours that are located within the sellar and para sellar region of the central nervous system.
A congenital disorder characterized by earlier than normal closure of some or all sutures of the infant skull.
Congenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital). The thyroid gland is a butterfly-shaped tissue in the lower neck. It makes iodine-containing hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). People with congenital hypothyroidism have lower-than-normal levels of these important hormones.Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80 to 85 percent of cases, the thyroid gland is absent, severely reduced in size (hypoplastic), or abnormally located. These cases are classified as thyroid dysgenesis. In the remainder of cases, a normal-sized or enlarged thyroid gland (goiter) is present, but production of thyroid hormones is decreased or absent. Most of these cases occur when one of several steps in the hormone synthesis process is impaired; these cases are classified as thyroid dyshormonogenesis. Less commonly, reduction or absence of thyroid hormone production is caused by impaired stimulation of the production process (which is normally done by a structure at the base of the brain called the pituitary gland), even though the process itself is unimpaired. These cases are classified as central (or pituitary) hypothyroidism.Signs and symptoms of congenital hypothyroidism result from the shortage of thyroid hormones. Affected babies may show no features of the condition, although some babies with congenital hypothyroidism are less active and sleep more than normal. They may have difficulty feeding and experience constipation. If untreated, congenital hypothyroidism can lead to intellectual disability and slow growth. In the United States and many other countries, all hospitals test newborns for congenital hypothyroidism. If treatment begins in the first two weeks after birth, infants usually develop normally.Congenital hypothyroidism can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic. Some common forms of syndromic hypothyroidism include Pendred syndrome, Bamforth-Lazarus syndrome, and brain-lung-thyroid syndrome.
Cri-du-chat syndrome was first described by Lejeune et al. (1963) as a hereditary congenital syndrome associated with deletion of part of the short arm of chromosome 5. The deletions can vary in size from extremely small and involving only band 5p15.2 to the entire short arm. Although the majority of deletions arise as new mutations, approximately 12% result from unbalanced segregation of translocations or recombination involving a pericentric inversion in one of the parents.
Crigler-Najjar syndrome is a severe condition characterized by high levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (called unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Crigler-Najjar syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia).Bilirubin has an orange-yellow tint, and hyperbilirubinemia causes yellowing of the skin and whites of the eyes (jaundice). In Crigler-Najjar syndrome, jaundice is apparent at birth or in infancy. Severe unconjugated hyperbilirubinemia can lead to a condition called kernicterus, which is a form of brain damage caused by the accumulation of unconjugated bilirubin in the brain and nerve tissues. Babies with kernicterus are often extremely tired (lethargic) and may have weak muscle tone (hypotonia). These babies may experience episodes of increased muscle tone (hypertonia) and arching of their backs. Kernicterus can lead to other neurological problems, including involuntary writhing movements of the body (choreoathetosis), hearing problems, or intellectual disability.Crigler-Najjar syndrome is divided into two types. Type 1 (CN1) is very severe, and affected individuals can die in childhood due to kernicterus, although with proper treatment, they may survive longer. Type 2 (CN2) is less severe. People with CN2 are less likely to develop kernicterus, and most affected individuals survive into adulthood.
A developmental malformation of the heart characterized by a twisted but not defective atrioventicular connection. The abnormal rotation of the ventricular mass around its long axis results in the crossing of the inflow streams of the two ventricles. Other features include hypoplasia of the TRICUSPID VALVE and RIGHT VENTRICLE.
A disease or state in which death is possible or imminent.
A chronic granulomatous inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea which may be bloody, vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration. Crohn's disease is thought to be an autoimmune disease, in which the body's immune system attacks the gastrointestinal tract, causing inflammation.
A synthetic fluorinated steroid that is used as a progestational hormone.
Infection associated with hospitalisation, not present or incubating prior to admission, but generally occurring more than 72 hours after admission.
A molecular interaction between a ligand molecule and a receptor molecule, where the ligand and receptor are not conventional partners. This interaction can occur because the ligand molecule shares structural features with the archetypal ligand.
Acute upper respiratory airways infection that results in the swelling of the larynx. It is usually caused by parainfluenza viruses. Signs include a characteristic barking cough and stridor.
Severe systemic manifestation of trauma and ischemia involving soft tissues, principally skeletal muscle, due to prolonged severe crushing. It leads to increased permeability of the cell membrane and to the release of potassium, enzymes, and myoglobin from within cells. Ischemic renal dysfunction secondary to hypotension and diminished renal perfusion results in acute tubular necrosis and uremia.
Liver cirrhosis with intrahepatic portal obstruction, HYPERTENSION, and patent UMBILICAL VEINS.
A condition characterized by the presence of abnormal quantities of CRYOGLOBULINS in the blood. Upon cold exposure, these abnormal proteins precipitate into the microvasculature leading to restricted blood flow in the exposed areas.
A substance that is used to protect from the effects of freezing, largely by preventing large ice crystals from forming.
An acute or chronic, localized or disseminated infection by Cryptococcus neoformans. Sites of involvement include the lungs, central nervous system and meninges, skin, and visceral organs.--2004
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
An infection that is caused by Cryptosporidium parvum or hominis, which is acquired by inhalation or ingestion of infectious spores, and which typically manifests as acute enteritis.
Plant extracts from several species, including genera STRYCHNOS and Chondodendron, which contain TETRAHYDROISOQUINOLINES that produce PARALYSIS of skeletal muscle. These extracts are toxic and must be used with the administration of artificial respiration.
Drugs that interrupt transmission at the skeletal neuromuscular junction without causing depolarization of the motor end plate. They prevent acetylcholine from triggering muscle contraction and are used as muscle relaxants during electroshock treatments, in convulsive states, and as anesthesia adjuvants.
A phytopolylphenol pigment isolated from the plant Curcuma longa, commonly known as turmeric, with a variety of pharmacologic properties. Curcumin blocks the formation of reactive-oxygen species, possesses anti-inflammatory properties as a result of inhibition of cyclooxygenases (COX) and other enzymes involved in inflammation; and disrupts cell signal transduction by various mechanisms including inhibition of protein kinase C. These effects may play a role in the agent's observed antineoplastic properties, which include inhibition of tumor cell proliferation and suppression of chemically induced carcinogenesis and tumor growth in animal models of cancer. (NCI04)
Acute stress DUODENAL ULCER, usually observed in patients with extensive third-degree burns.
A condition caused by prolonged exposure to excess levels of cortisol (HYDROCORTISONE) or other GLUCOCORTICOIDS from endogenous or exogenous sources. It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of ADRENOCORTICOTROPIN and those that are ACTH-independent.
A congenital or acquired disorder affecting the elastic fibers of the skin. It is characterized by loss of elasticity resulting in loosening and folding of the skin.
A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule.
A direct-acting SMOOTH MUSCLE relaxant used to dilate BLOOD VESSELS.
An analgesic with mixed narcotic agonist-antagonist properties.
A histamine H1 antagonist given by mouth or parenterally for the control of postoperative and drug-induced vomiting and in motion sickness. (From Martindale, The Extra Pharmacopoeia, 30th ed, p935)
A cytarabine congener prodrug with antineoplastic activity. Upon administration, ancitabine is slowly hydrolyzed into cytarabine, which is converted to the active triphosphate form and competes with deoxycytidine triphosphate for incorporation into DNA. Because the arabinose sugar sterically hinders the rotation of the molecule within DNA, DNA replication ceases, specifically during the S phase of the cell cycle. This agent also inhibits DNA and RNA polymerases, resulting in a decrease in cell growth. Compared to cytarabine, a more prolonged, consistent cytarabine-mediated therapeutic effect may be achieved with ancitabine because of the slow hydrolytic conversion of ancitabine to cytarabine.
A gonadal stimulant and inducer of ovulation. It is used in the treatment of infertility and amenorrhea, but is thought to be less effective than CLOMIPHENE.
A non-metabolizable synthetic amino acid, formed through the cyclization of the amino acid leucine, with immunosuppressive, antineoplastic, and cytostatic activities. Cycloleucine competitively inhibits the enzyme methionine adenosyltransferase, resulting in the inhibition of S-adenosylmethionine (SAM) synthesis from methionine and ATP, and subsequent nucleic acid methylation and polyamine production; RNA, and perhaps to a lesser extent, DNA biosyntheses and cell cycle progression are finally disrupted. This agent is also a competitive inhibitor at the glycine modulatory site of the N-methyl-D-aspartate (NMDA) receptor.
A benzothiadiazine sulfonamide derivative belonging to the class of the thiazide diuretics.
A parasympatholytic anticholinergic used solely to obtain mydriasis or cycloplegia.
A synthetic alkylating agent chemically related to the nitrogen mustards with antineoplastic and immunosuppressive activities. In the liver, cyclophosphamide is converted to the active metabolites aldophosphamide and phosphoramide mustard, which bind to DNA, thereby inhibiting DNA replication and initiating cell death.
C3H6; a flammable moderately toxic narcotic colorless gas used in organic synthesis and as an anesthetic.
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).
A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection.
An affective disorder characterized by periods of depression and hypomania. These may be separated by periods of normal mood.
A malignant tumor arising from the epithelial cells. Microscopically, the neoplastic epithelial cells form cylindrical spatial configurations (cribriform or classic type of adenoid cystic carcinoma), cordlike structures (tubular type of adenoid cystic carcinoma), or solid structures (basaloid variant of adenoid cystic carcinoma). Adenoid cystic carcinomas mostly occur in the salivary glands. Other primary sites of involvement include the lacrimal gland, the larynx, and the lungs. Adenoid cystic carcinomas spread along nerve sheaths, resulting in severe pain, and they tend to recur. Lymph node metastases are unusual; hematogenous tumor spread is characteristic.
A cardiotonic cardiac glycoside found in STROPHANTHUS. The aglycone is STROPHANTHIN.
A serotonin antagonist and a histamine H1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc.
A synthetic steroidal anti-androgen with antineoplastic activity. Cyproterone, in its acetate form, binds the androgen receptor (AR), thereby preventing androgen-induced receptor activation and inhibiting the growth of testosterone-sensitive tumor cells. This agent also exerts progesterogenic activity, resulting in a reduction in testicular androgen secretion and total androgen blockade. (NCI04)
A malignant cystic epithelial neoplasm arising from the glandular epithelium. The malignant epithelial cells invade the stroma. The cystic spaces contain serous or mucinous fluid. Representative examples include ovarian and pancreatic cystadenocarcinomas.
A benign or borderline cystic epithelial neoplasm arising from the glandular epithelium. The epithelial cells line the cystic spaces which contain serous or mucinous fluid. Representative examples include ovarian and pancreatic cystadenomas.
A benign or low malignant potential cystic epithelial neoplasm composed of cells which contain intracytoplasmic mucin. It may arise from the ovary, pancreas, appendix, and lung.
A serous or mucinous benign or low malignant potential cystic epithelial neoplasm. It is characterized by the presence of glandular epithelial cells forming papillary structures.
A radiation-protective agent that interferes with sulfhydryl enzymes. It may also protect against carbon tetrachloride liver damage.
Proposed as an adjuvant to cancer chemotherapy; may have radiation protective properties.
A cytastin subtype found at high levels in the SKIN and in BLOOD CELLS. Cystatin A incorporates into the cornified cell envelope of stratified squamous epithelial cells and may play a role in bacteriostatic properties of skin.
A homologous group of endogenous CYSTEINE PROTEINASE INHIBITORS. The cystatins inhibit most CYSTEINE ENDOPEPTIDASES such as PAPAIN, and other peptidases which have a sulfhydryl group at the active site.
A mercaptoethylamine compound that is endogenously derived from the COENZYME A degradative pathway. The fact that cysteamine is readily transported into LYSOSOMES where it reacts with CYSTINE to form cysteine-cysteamine disulfide and CYSTEINE has led to its use in CYSTINE DEPLETING AGENTS for the treatment of CYSTINOSIS.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
A congenital malformation that is present in the lungs of the newborn. It is characterized by a spectrum of lesions that range from single or multiple cysts to bulky overgrowth of bronchiole-like structures. Signs and symptoms include respiratory distress, recurrent pulmonary infections, dyspnea, and failure to thrive.
Benign endometrial hyperplasia characterized by the presence of cystically dilated glands.
Cystic fibrosis (CF) is a multisystem disease affecting epithelia of the respiratory tract, exocrine pancreas, intestine, hepatobiliary system, and exocrine sweat glands. Morbidities include progressive obstructive lung disease with bronchiectasis, frequent hospitalizations for pulmonary disease, pancreatic insufficiency and malnutrition, recurrent sinusitis and bronchitis, and male infertility. Pulmonary disease is the major cause of morbidity and mortality in CF. Meconium ileus occurs at birth in 15%-20% of newborns with CF. More than 95% of males with CF are infertile. Congenital absence of the vas deferens (CAVD) is generally identified during evaluation of infertility or as an incidental finding at the time of a surgical procedure. Hypoplasia or aplasia of the vas deferens and seminal vesicles may occur either bilaterally or unilaterally. Testicular development and function and spermatogenesis are usually normal.
A parasitic infection caused by the larval form of Taenia solium. It is a disseminated infection affecting the central nervous system, subcutaneous tissues, lungs, heart and liver. The most serious complications result from infection of the brain parenchyma. Patients may develop seizures, hydrocephalus, encephalopathy and meningoencephalitis.
A covalently linked dimeric nonessential amino acid formed by the oxidation of CYSTEINE. Two molecules of cysteine are joined together by a disulfide bridge to form cystine.
Cystinuria is an autosomal disorder characterized by impaired epithelial cell transport of cystine and dibasic amino acids (lysine, ornithine, and arginine) in the proximal renal tubule and gastrointestinal tract. The impaired renal reabsorption of cystine and its low solubility causes the formation of calculi in the urinary tract, resulting in obstructive uropathy, pyelonephritis, and, rarely, renal failure (summary by Barbosa et al., 2012).
A HERNIA-like condition in which the weakened pelvic muscles cause the URINARY BLADDER to drop from its normal position. Fallen urinary bladder is more common in females with the bladder dropping into the VAGINA and less common in males with the bladder dropping into the SCROTUM.
A benign, borderline, or malignant fibroepithelial neoplasm arising from the breast and rarely the prostate gland. It may recur following resection. The recurrence rates are higher for borderline and malignant phyllodes tumors. In borderline and malignant phyllodes tumors metastases to distant anatomic sites can occur. The incidence of metastases is higher in malignant phyllodes tumors.
A sac-like closed membranous structure that may be empty or contain fluid or amorphous material.
A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)
A nutritional supplement and source of choline and cytidine with potential neuroprotective and nootropic activity. Citicoline, also known as cytidine-5-diphosphocholine or CDP-choline, is hydrolyzed into cytidine and choline in the intestine. Following absorption, both cytidine and choline are dispersed, utilized in various biosynthesis pathways, and cross the blood-brain barrier for resynthesis into citicoline in the brain, which is the rate-limiting product in the synthesis of phosphatidylcholine. This agent also increases acetylcholine (Ach), norepinephrine (NE) and dopamine levels in the central nervous system (CNS). In addition, citicoline is involved in the preservation of sphingomyelin and cardiolipin and the restoration of Na+/K+-ATPase activity. Citicoline also increases glutathione synthesis and glutathione reductase activity, and exerts antiapoptotic effects.
A cytotoxic member of the CYTOCHALASINS.
11- to 14-membered macrocyclic lactones with a fused isoindolone. Members with INDOLES attached at the C10 position are called chaetoglobosins. They are produced by various fungi. Some members interact with ACTIN and inhibit CYTOKINESIS.
A herpesvirus infection caused by Cytomegalovirus. Healthy individuals generally do not produce symptoms. However, the infection may be life-threatening in affected immunocompromised patients. The virus may cause retinitis, esophagitis, gastritis, and colitis. Morphologically, it is characterized by the presence of intranuclear inclusion bodies.
Structural changes in host cells that are caused by viral invasion.
A laboratory test result indicating an abnormally low quantity of circulating blood cells.
Compounds that inhibit or prevent the proliferation of CELLS.
A triazene derivative with antineoplastic activity. Dacarbazine alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis. (NCI04)
A synthetic androgen derived from ethinyl testosterone. Danazol indirectly reduces estrogen production by decreasing pituitary secretion of follicle-stimulating hormone and luteinizing hormone, and binds to sex hormone receptors in target tissues, thereby exhibiting antiestrogenic, anabolic and weakly androgenic effects. (NCI04)
Dandy-Walker malformation is defined by hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of the fourth ventricle. Affected individuals often have motor deficits such as delayed motor development, hypotonia, and ataxia; about half have mental retardation and some have hydrocephalus. DWM is a heterogeneous disorder. The low empiric recurrence risk of approximately 1 to 2% for nonsyndromic DWM suggests that mendelian inheritance is unlikely (summary by Murray et al., 1985).
A hydantoin derivative and direct-acting skeletal muscle relaxant. Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor 1, and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction.
The sodium salt form of dantrolene, a hydantoin derivative and direct-acting skeletal muscle relaxant. Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor 1, and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction.
A sulfone active against a wide range of bacteria but mainly employed for its actions against MYCOBACTERIUM LEPRAE. Its mechanism of action is probably similar to that of the SULFONAMIDES which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with PYRIMETHAMINE in the treatment of malaria. (From Martindale, The Extra Pharmacopoeia, 30th ed, p157-8)
A general term for the complete loss of the ability to hear from both ears.
Sensorineural hearing loss which develops suddenly over a period of hours or a few days. It varies in severity from mild to total deafness. Sudden deafness can be due to head trauma, vascular diseases, infections, or can appear without obvious cause or warning.
An antidepressive agent that has also been used in the treatment of movement disorders. The mechanism of action is not well understood.
An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.
The loss of calcium salts from bones and teeth. Bacteria may be responsible for this occurrence in teeth. Old age may be a factor contributing to calcium loss, as is the presence of diseases such as rheumatoid arthritis.
A condition characterized by abnormal posturing of the limbs that is associated with injury to the brainstem. This may occur as a clinical manifestation or induced experimentally in animals. The extensor reflexes are exaggerated leading to rigid extension of the limbs accompanied by hyperreflexia and opisthotonus. This condition is usually caused by lesions which occur in the region of the brainstem that lies between the red nuclei and the vestibular nuclei. In contrast, decorticate rigidity is characterized by flexion of the elbows and wrists with extension of the legs and feet. The causative lesion for this condition is located above the red nuclei and usually consists of diffuse cerebral damage. (From Adams et al., Principles of Neurology, 6th ed, p358)
A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death.
A type of ulcer that is caused when an area of skin is subject to pressure over a prolonged period of time, ranging in range in severity from patches of discolored skin to open wounds that expose the underlying bone or muscle. The most common sites are the sacrum, coccyx, heels and the hips.
A compound used as a topical insect repellent that may cause irritation to eyes and mucous membranes, but not to the skin.
The mesylate salt of an iron-chelating agent that binds free iron in a stable complex, preventing it from engaging in chemical reactions. Deferoxamine chelates iron from intra-lysosomal ferritin and ferrioxamine, a water-soluble complex excreted by the kidneys and in the feces via the bile. This agent does not readily chelate iron bound to transferrin, hemoglobin, myoglobin or cytochrome.
A condition produced by dietary or metabolic deficiency. The term includes all diseases caused by an insufficient supply of essential nutrients, i.e., protein (or amino acids), vitamins, and minerals. It also includes an inadequacy of calories. (From Dorland, 27th ed; Stedman, 25th ed)
Disturbance of cell integrity and deterioration of normal tissue, cells or organs.
A symptom referring to difficulty in swallowing. It may be observed in patients with stroke, motor neuron disorders, cancer of the throat or mouth, head and neck injuries, Parkinson disease, and multiple sclerosis.
A condition resulting from the excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
The reversibly oxidized form of ascorbic acid. It is the lactone of 2,3-DIKETOGULONIC ACID and has antiscorbutic activity in man on oral ingestion.
A semisynthetic bile acid made from cholic acid. It is used as a cholagogue, hydrocholeretic, diuretic, and as a diagnostic aid.
A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.
Dejerine-Sottas neuropathy is a demyelinating peripheral neuropathy with onset in infancy. It can show autosomal dominant or recessive inheritance. Affected individuals have delayed motor development due to severe distal motor and sensory impairment, resulting in difficulties in gait. Some patients have generalized hypotonia in infancy. Other features may include pes cavus, scoliosis, and sensory ataxia. Nerve conduction velocities are severely decreased (sometimes less than 10 m/s), and sural nerve biopsy shows severe loss of myelinated fibers (summary by Baets et al., 2011).
Dosage forms of a drug that act over a period of time by controlled-release processes or technology.
A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2)
INFLAMMATION of the LIVER in humans caused by HEPATITIS DELTA VIRUS, a defective RNA virus that can only infect HEPATITIS B patients. For its viral coating, hepatitis delta virus requires the HEPATITIS B SURFACE ANTIGENS produced by these patients. Hepatitis D can occur either concomitantly with (coinfection) or subsequent to (superinfection) hepatitis B infection. Similar to hepatitis B, it is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.
A disorder characterized by the presence of one or more nonbizarre delusions that persist for at least 1 month; the delusion(s) are not due to schizophrenia or a mood disorder, and do not impair psychosocial functioning apart from the ramifications of the delusion(s).
A belief that is pathological and is held despite evidence to the contrary.
A colchicine analog with potential antimitotic and antineoplastic activities. Demecolcine acid binds to the colchicine-binding site of tubulin, inhibiting its polymerization into microtubules, causing cell cycle arrest at metaphase and preventing cell division.
A common form of dementia caused by multiple cortical or subcortical cerebral infarctions.
The presence of dementia in an individual younger than age sixty five.
Loss of intellectual abilities in an elderly person, interfering with this person's activities.
A degenerative vascular disorder affecting the brain. It is caused by the blockage of the blood supply to the brain. It is manifested with decline of memory and cognitive functions.
An intermediate in the metabolism of DIAZEPAM to OXAZEPAM. It may have actions similar to those of diazepam.
Any condition in which there is degeneration of the myelin sheath that covers the nerves of the central nervous system.
A broad group of disorders that affect the myelin sheaths that cover the neurons. Myelin sheathes cover neuronal axons in the central and peripheral nervous system and function to increase travelling impulse speeds. Disruption of this sheath impairs neuronal transmission and can result in disorders such as multiple sclerosis and Guillain-Barre syndrome, among others.
Breakdown, or abnormal development, of a nerve fiber myelin sheath.
An acute febrile disease transmitted by the bite of AEDES mosquitoes infected with DENGUE VIRUS. It is self-limiting and characterized by fever, myalgia, headache, and rash. SEVERE DENGUE is a more virulent form of dengue.
An abnormality of the incisor characterized by invagination of the enamel, giving a radiographic appearance that suggests a tooth within a tooth.
Abnormal concretion or calcified deposit that forms around the teeth or dental prostheses.
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Accumulations of microflora that lead to pathological plaque and calculus which cause PERIODONTAL DISEASES. It can be considered a type of BIOFILMS. It is subtly distinguished from the protective DENTAL PELLICLE.
A form of amelogenesis imperfecta characterized by incomplete formation of the dental enamel and transmitted as an X-linked or autosomal dominant trait.
An abnormal passage in the oral cavity on the gingiva.
The seepage of fluids, debris, and micro-organisms between the walls of a prepared dental cavity and the restoration.
Dental occlusion in which the occlusal contact of the teeth on the working side of the jaw is accompanied by the harmonious contact of the teeth on the opposite (balancing) side. (From Jablonski, Dictionary of Dentistry, 1992, p556)
A biofilm that contains numerous microorganisms that adheres to the teeth.
CALCINOSIS of the DENTAL PULP or ROOT CANAL.
A disorder that affects the dental pulp tissue. Examples include inflammation, calcification, and dental pulp exposure.
The result of pathological changes in the hard tissue of a tooth caused by carious lesions, mechanical factors, or trauma, which render the pulp susceptible to bacterial invasion from the external environment.
Death of pulp tissue with or without bacterial invasion. When the necrosis is due to ischemia with superimposed bacterial infection, it is referred to as pulp gangrene. When the necrosis is non-bacterial in origin, it is called pulp mummification.
Most common follicular odontogenic cyst. Occurs in relation to a partially erupted or unerupted tooth with at least the crown of the tooth to which the cyst is attached protruding into the cystic cavity. May give rise to an ameloblastoma and, in rare instances, undergo malignant transformation.
Developmental dysplasia of dentin affecting only the primary dentition.
Pain associated with exposed DENTIN surfaces of the teeth.
Dentin formed by normal pulp after completion of root end formation.
A congenital tooth development disorder caused by mutations in the DSPP gene. The teeth are weak, discolored, and translucent.
Substances used to clean dentures; they are usually alkaline peroxides or hypochlorites, may contain enzymes and release oxygen. Use also for sonic action cleaners.
A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent.
A non-metabolizable glucose analog in which the hydroxyl group at position 2 of glucose is replaced by hydrogen, with potential glycolysis inhibiting and antineoplastic activities. Although the exact mechanism of action has yet to be fully elucidated, upon administration of 2-deoxy-D-glucose (2-DG), this agent competes with glucose for uptake by proliferating cells, such as tumor cells. 2-DG inhibits the first step of glycolysis and therefore prevents cellular energy production, which may result in decreased tumor cell proliferation.
Enzymes that catalyze the hydrolytic cleavage of phosphodiester bond linkages in the DNA backbone. Deoxyribonucleases belong to a larger family of nucleases, which cleave DNA bases at various positions in the DNA backbone.
A disorder characterized by an enduring pattern of an extreme need to be taken care of together with fear of separation that lead the individual to urgently seek out and submit to another person and allow that person to make decisions that impact all areas of the individual's life.
State in which an individual perceives or experiences a sensation of unreality concerning the self or the environment; it is seen in disorders such as schizophrenia, affection disorders, organic mental disorders, and personality disorders. (APA, Thesaurus of Psychological Index Terms, 8th ed.)
Depression (also known as major depression or major depressive disorder) is a psychiatric disorder that affects mood, behavior, and overall health. It causes prolonged feelings of sadness, emptiness, or hopelessness, and a loss of interest in activities that were once enjoyed. People with depression may also have changes in appetite (leading to overeating or not eating enough), changes in sleeping patterns (sleeping too much or not being able to sleep), loss of energy, and difficulty concentrating. Although depression is considered primarily a mental health disorder, it can also have physical features including headaches, other unexplained aches and pains, unusually slow or fast movements, and digestive problems. To be diagnosed with depression, an individual must have signs and symptoms nearly every day for at least 2 weeks. However, the features of this condition vary widely.Depression most commonly begins in late adolescence or early adulthood, although it can appear at any age. If untreated, episodes of depression can last for weeks, months, or years, and can go away and come back (recur). Affected individuals may have difficulty functioning in their daily lives, including at school or work. People with depression have a higher risk of substance abuse problems and dying by suicide than the general population.Several health conditions are closely related to depression or have depression as a characteristic feature. These include dysthymia (which has long-lasting signs and symptoms that are similar to, but not as severe as, those of depression), perinatal or postpartum depression (which occurs around or following the birth of a child), seasonal affective disorder (which is triggered by the changing of the seasons), bipolar disorder (which can include both ""highs,"" or manic episodes, and depressive episodes), and generalized anxiety disorder. In people with schizoaffective disorder, depression or another mood disorder occurs together with features of schizophrenia (a brain disorder that affects a person's thinking, sense of self, and perceptions).
The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.
Depression which is considered strictly biological.
Form of depression in those MIDDLE AGE with feelings of ANXIETY.
Depression precipitated by events in a person's life.
An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.
A topical bacteriostat that is available as various salts. It is used in wound dressings and mouth infections and may also have antifungal action, but may cause skin ulceration.
The presence of inflammation of the skin. That is, an abnormality of the skin resulting from the local accumulation of fluid, plasma proteins, and leukocytes.
A generalized inflammatory cutaneous disorder characterized by erythema and desquamation.
A chronic autoimmune skin disorder characterized by the development of pruritic papulovesicular and bullous lesions in the elbows, knees, buttocks, and back. It is associated with an increased expression of HLA-A1, HLA-B8, and HLA-DR3 antibodies.
Adverse cutaneous reactions caused by ingestion, parenteral use, or local application of a drug. These may assume various morphologic patterns and produce various types of lesions.
Atopic dermatitis (ATOD), also known as eczema, is a common chronic pruritic inflammatory skin disease with a strong genetic component. Onset typically occurs during the first 2 years of life (review by Soderhall et al., 2007). Genetic Heterogeneity of Atopic Dermatitis Many inflammatory diseases, such as atopic eczema, are genetically complex, with multiple alleles at several loci thought to be involved in their pathogenesis. Several susceptibility loci for atopic dermatitis have been identified: ATOD1 on chromosome 3q21, ATOD2 (605803) on chromosome 1q21, ATOD3 (605804) on chromosome 20p, ATOD4 (605805) on chromosome 17q25.3, ATOD5 (603165) on chromosome 13q12-q14, ATOD6 (605845) on chromosome 5q31-q33, ATOD7 (613064) on chromosome 11q13.5, ATOD8 (613518) on chromosome 4q22.1, and ATOD9 (613519) on chromosome 3p24.
A polymorphic pattern of inflammatory reaction of the skin in response to contact with external irritants or allergens.
Drugs used to treat or prevent skin disorders or for the routine care of skin.
Superficial infections of the skin or its appendages by any of various fungi.
A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. (From Adams et al., Principles of Neurology, 6th ed, pp1405-6)
Dermatophytosis involving the stratum corneum of the skin of the groin and perianal area.
Dermatophytosis involving the stratum corneum of the skin of the scalp and beard area.
A chronic autoimmune phenomenon characterized by fibrosis (or hardening) and vascular alterations of the skin. [HPO:sdoelken]
A benign skin condition commonly seen in dark-skinned individuals that is characterized by multiple small hyperpigmented papular lesions resembling seborrheic keratosis on the face and upper body.
A congenital subcutaneous cyst that arises from entrapment of skin along the lines of embryonic fusion. In contrast to epidermal cysts, dermoid cysts tend to contain various adnexal structures such as hair, sebaceous, eccrine or apocrine glands. Dermoid cysts are present at birth, and are indolent, firm, deep, subcutaneous nodules. They are often located on the head and neck, and rarely in the anogenital area. Dermoid cysts are\nslowly progressive and can grow to a size of 1 to 4 cm.
A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.
Deacetyllanatoside C. A cardiotonic glycoside from the leaves of Digitalis lanata.
A synthetic analog of the pituitary hormone, ARGININE VASOPRESSIN. Its action is mediated by the VASOPRESSIN receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating FACTOR VIII and VON WILLEBRAND FACTOR.
A nonfluorinated corticosteroid anti-inflammatory agent used topically for DERMATOSES.
A synthetic glucocorticoid receptor agonist with metabolic, anti-inflammatory and immunosuppressive activity. Desoximetasone activates specific intracellular receptors, which bind to distinct sites on DNA to modify gene transcription. This results in an induction of the synthesis of anti-inflammatory proteins and suppression of the synthesis of inflammatory mediators. This leads to an overall reduction in chronic inflammation and autoimmune reactions. Desoximetasone is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses.
A C-21 steroid hormone synthesized by the adrenal gland that is a precursor for cortisol and aldosterone and has potential mineralocorticoid activity.
A disorder characterized by an impairment in the development of an individual's motor coordination skills; this impairment in motor development is not due to a medical condition.
A synthetic adrenal corticosteroid with potent anti-inflammatory properties. In addition to binding to specific nuclear steroid receptors, dexamethasone also interferes with NF-kB activation and apoptotic pathways. This agent lacks the salt-retaining properties of other related adrenal hormones. (NCI04)
An anti-inflammatory, anti-allergic glucocorticoid that can be administered orally, by inhalation, locally, and parenterally. It may cause water and salt retention.
The hydrochloride salt form of phenylpropanolamine, an alpha- and beta-adrenergic receptor agonist with sympathomimetic activity. Phenylpropanolamine binds to and activates alpha- and beta-adrenergic receptors in the mucosa of the respiratory tract resulting in vasoconstriction and reduction in swelling of nasal mucous membranes and reduction in tissue hyperemia, edema, and nasal congestion. This agent also stimulates the release of norepinephrine from its storage sites resulting in the effects already described. Finally, phenylpropanolamine indirectly stimulates beta-receptors producing tachycardia and a positive inotropic effect.
A muscarinic antagonist that has been used to treat neuroleptic-induced parkinsonism. Benzetimide is the (-)-enantimorph of dexetimide.
The S-isomer of FENFLURAMINE. It is a serotonin agonist and is used as an anorectic. Unlike fenfluramine, it does not possess any catecholamine agonist activity.
A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes.
The salt of the dextro-isomer of amphetamine and sympathomimetic amine with CNS stimulating properties. Dextroamphetamine sulphate acts by facilitating the release of catecholamines, particularly noradrenaline and dopamine, from nerve terminals in the brain and inhibits their uptake. This leads to an increase in motor activity, causes euphoria, mental alertness and excitement and suppresses appetite. This drug causes dependence and may cause an increase in heart rate and blood pressure. It is used in the treatment of narcolepsy and attention deficit hyperactivity disorder.
A synthetic substance related to natural sympathomimetic amines and the synthetic agent amphetamine. In the central nervous system (CNS), dextroamphetamine induces the release of dopamine within the mesocorticolimbic system, a major component of the brain reward system, resulting in measurable behavioral changes such as euphoria. As a CNS stimulant, this agent may increase blood pressure and reduce appetite. Similar to other amphetamines, dextroamphetamine has a high potential for abuse, dependence, and addiction if used in large doses over extended periods of time. (NCI04)
A congenital defect in which the heart is located on the right side of the THORAX instead of on the left side (levocardia, the normal position). When dextrocardia is accompanied with inverted HEART ATRIA, a right-sided STOMACH, and a left-sided LIVER, the combination is called dextrocardia with SITUS INVERSUS. Dextrocardia may adversely affect other thoracic organs.
A synthetic, methylated dextrorotary analogue of levorphanol, a substance related to codeine and a non-opioid derivate of morphine. Dextromethorphan exhibits antitussive activity and is devoid of analgesic or addictive property. This agent crosses the blood-brain-barrier and activates sigma opioid receptors on the cough center in the central nervous system, thereby suppressing the cough reflex.
An opioid analgesic structurally related to METHADONE and used in the treatment of severe pain. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1070)
An overriding aorta is a congenital heart defect where the aorta is positioned directly over a ventricular septal defect, instead of over the left ventricle. The result is that the aorta receives some blood from the right ventricle, which reduces the amount of oxygen in the blood. It is one of the four conditions of the Tetralogy of Fallot. The aortic root can be displaced toward the front (anteriorly) or directly above the septal defect, but it is always abnormally located to the right of the root of the pulmonary artery. The degree of override is quite variable, with 5-95% of the valve being connected to the right ventricle.
Dextro form of levorphanol. It acts as a noncompetitive NMDA receptor antagonist, among other effects, and has been proposed as a neuroprotective agent. It is also a metabolite of DEXTROMETHORPHAN.
The dextrorotary isomer of the synthetic THYROXINE.
A state of excessive water intake and hypotonic (dilute) polyuria. Diabetes insipidus may be due to failure of vasopressin (AVP) release (central or neurogenic diabetes insipidus) or to a failure of the kidney to respond to AVP (nephrogenic diabetes insipidus).
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
The type of diabetes mellitus called IDDM is a disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. It is a genetically heterogeneous autoimmune disease affecting about 0.3% of Caucasian populations (Todd, 1990). Genetic studies of IDDM have focused on the identification of loci associated with increased susceptibility to this multifactorial phenotype. The classical phenotype of diabetes mellitus is polydipsia, polyphagia, and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
A rare syndrome characterized by almost complete absence of body fat, accentuated muscularity, insulin-resistant diabetes, hyperlipidemia, hepatomegaly, and hypermetabolism.
Type 2 diabetes is a disorder characterized by abnormally high blood sugar levels. In this form of diabetes, the body stops using and making insulin properly. Insulin is a hormone produced in the pancreas that helps regulate blood sugar levels. Specifically, insulin controls how much glucose (a type of sugar) is passed from the blood into cells, where it is used as an energy source. When blood sugar levels are high (such as after a meal), the pancreas releases insulin to move the excess glucose into cells, which reduces the amount of glucose in the blood.Most people who develop type 2 diabetes first have insulin resistance, a condition in which the body's cells use insulin less efficiently than normal. As insulin resistance develops, more and more insulin is needed to keep blood sugar levels in the normal range. To keep up with the increasing need, insulin-producing cells in the pancreas (called beta cells) make larger amounts of insulin. Over time, the beta cells become less able to respond to blood sugar changes, leading to an insulin shortage that prevents the body from reducing blood sugar levels effectively. Most people have some insulin resistance as they age, but inadequate exercise and excessive weight gain make it worse, greatly increasing the likelihood of developing type 2 diabetes.Type 2 diabetes can occur at any age, but it most commonly begins in middle age or later. Signs and symptoms develop slowly over years. They include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet (diabetic neuropathy), sores that do not heal well, and weight loss. If blood sugar levels are not controlled through medication or diet, type 2 diabetes can cause long-lasting (chronic) health problems including heart disease and stroke; nerve damage; and damage to the kidneys, eyes, and other parts of the body.
Vascular disorders resulting from diabetes mellitus.
rare, usually bilateral, opacity shaped like a snowflake, affecting the anterior and posterior cortices of young diabetics; sometimes it can be reversed when the blood glucose is brought under control, but in most cases it progresses rapidly to a mature cataract.
A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by KETOSIS; DEHYDRATION; and depressed consciousness leading to COMA.
KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.
A chronic, pathological complication associated with diabetes mellitus, where nerve damages are incurred due to diabetic microvascular injury involving small blood vessels that supply these nerves, resulting in peripheral and/or autonomic nerve dysfunction.
A chronic, pathological complication associated with diabetes mellitus, where retinal damages are incurred due to microaneurysms in the vasculature of the retina, progressively leading to abnormal blood vessel growth, and swelling and leaking of fluid from blood vessels, resulting in vision loss or blindness.
A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed)
Solutions prepared for exchange across a semipermeable membrane of solutes below a molecular size determined by the cutoff threshold of the membrane material.
Anthelmintic. It has been shown to be useful in fasciola infections in sheep.
A sulfhydryl reagent which oxidizes sulfhydryl groups to the disulfide form. It is a radiation-sensitizing agent of anoxic bacterial and mammalian cells.
A bifunctional hexitol derivative with potential antineoplastic activity. Dianhydrogalactitol alkylates and cross-links DNA via an epoxide group during all phases of the cell cycle, resulting in disruption of DNA function and cell cycle arrest. (NCI04)
A type of irritant dermatitis localized to the area in contact with a diaper and occurring most often as a reaction to prolonged contact with urine, feces, or retained soap or detergent.
A congenital abnormality characterized by the elevation of the DIAPHRAGM dome. It is the result of a thinned diaphragmatic muscle and injured PHRENIC NERVE, allowing the intra-abdominal viscera to push the diaphragm upward against the LUNG.
Camurati-Engelmann disease (CED) is characterized by hyperostosis of the long bones and the skull, proximal muscle weakness, limb pain, a wide-based, waddling gait, and joint contractures. Facial features such as macrocephaly, frontal bossing, enlargement of the mandible, proptosis, and cranial nerve impingement resulting in facial palsy are seen in severely affected individuals later in life.
Abnormally increased frequency of loose or watery bowel movements.
DIARRHEA occurring in infants from newborn to 24-months old.
An often clinically aggressive neuroendocrine tumor located in the pancreas or small intestine. It is composed of cells containing vasoactive intestinal peptide. It may cause intractable diarrhea and metabolic disturbances.
An abnormal opening or fissure between two adjacent teeth.
A rare congenital abnormality in which the spinal cord is split in half by fibrous or bony tissue. It may present as an isolated phenomenon or in association with spina bifida.
A benzodiazepine derivative with anti-anxiety, sedative, hypnotic and anticonvulsant properties. Diazepam potentiates the inhibitory activities of gamma-aminobutyric acid (GABA) by binding to the GABA receptor, located in the limbic system and the hypothalamus. This increases the frequency of chloride channel opening, allowing the flow of chloride ions into the neuron and ultimately leading to membrane hyperpolarization and a decrease in neuronal excitability.
An L-glutamine diazo analogue amino acid antibiotic isolated from a species of the bacterial genus Streptomyces with potential antineoplastic activity. Diazooxonorleucine inhibits several glutamine-dependent biosynthetic pathways involved in the syntheses of D-glucosamine phosphate, purines and pyrimidines. This agent inhibits phosphate-activated glutaminase, a key enzyme for the synthesis of releasable glutamine, depleting cells of this essential amino acid and reducing their capacity to proliferate.
A benzothiadiazine derivate with antihypertensive and hyperglycemic activities. Diazoxide increases membrane permeability to potassium ions in vascular smooth muscle, thereby stabilizing the membrane action potential and preventing vascular smooth muscle contraction; this results in peripheral vasodilatation and decreases in peripheral vascular resistance. This agent also inhibits insulin release by interacting with ATP-sensitive potassium channels of pancreatic islet beta-cells.
A family of tricyclic hydrocarbons whose members include many of the commonly used tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC).
At low concentrations, this compound inhibits reduction of conventional hydrophilic electron acceptors, probably acting as a plastoquinone antagonist. At higher concentrations, it acts as an electron acceptor, intercepting electrons either before or at the site of its inhibitory activity.
A local anesthetic of the amide type now generally used for surface anesthesia. It is one of the most potent and toxic of the long-acting local anesthetics and its parenteral use is restricted to spinal anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1006)
A plasticizer used in most plastics and found in water, air, soil, plants and animals. It may have some adverse effects with long-term exposure.
A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)
A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.
A nontoxic laxative vermicide of chlorinated phenol compound. Dichlorophen is used as a veterinary fungicide, anthelmintic, and anti-protozoan, as well as an ingredient in antimicrobial soaps and shampoos. This agent probably acts by increasing the clearing of intestinal contents, thereby eradicating tapeworm infections from the intestines.
An RNA polymerase II transcriptional inhibitor. This compound terminates transcription prematurely by selective inhibition of RNA synthesis. It is used in research to study underlying mechanisms of cellular regulation.
A carbonic anhydrase inhibitor that is used in the treatment of glaucoma.
A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.
Infection with flukes of the genus Dicrocoelium.
Infection with nematodes of the genus DICTYOCAULUS. In deer, cattle, sheep, and horses the bronchi are the site of infestation.
A carboxylic acid derivative and a selective anticholinergic with antispasmodic activity. Dicyclomine blocks acetylcholine from binding to muscarinic receptors on smooth muscle. This agent has a direct relaxing effect on smooth muscle and therefore prevents spasms in the muscles of the gastrointestinal tract, inhibits gastrointestinal propulsive motility, decreases gastric acid secretion and controls excessive pharyngeal, tracheal and bronchial secretion.
A prodrug form of didanosine, a nucleoside reverse transcriptase inhibitor analog of adenosine.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.
A synthetic, non-steroidal estrogen structurally related to stilbestrol. It is used, usually as the cream, in the treatment of menopausal and postmenopausal symptoms.
Gastrointestinal infection with organisms of the genus DIENTAMOEBA.
A phase of the ESTROUS CYCLES that follows METESTRUS. Diestrus is a period of sexual quiescence separating phases of ESTRUS in polyestrous animals.
Diets which become fashionable, but which are not necessarily nutritious.(Lehninger 1982, page 484)
An approach to nutrition based on whole cereal grains, beans, cooked vegetables and the Chinese YIN-YANG principle. It advocates a diet consisting of organic and locally grown foods, seasonal vegetables, complex carbohydrates, and fewer fats, sugars, and chemically processed foods.
Preservative for wines, soft drinks, and fruit juices and a gentle esterifying agent.
An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa.
A sulfhydryl-containing carbamate that is the primary in vivo metabolite of disulfiram. Diethyldithiocarbamate chelates zinc, thereby inhibiting metalloproteinases, thereby preventing the degradation of the extracellular matrix and inhibiting an initial step in cancer metastasis and angiogenesis. A known inhibitor of superoxide dismutase, this agent can either potentiate or protect against cell oxidative damage caused by ionizing radiation, depending on the time of administration. (NCI04)
A appetite depressant considered to produce less central nervous system disturbance than most drugs in this therapeutic category. It is also considered to be among the safest for patients with hypertension. (From AMA Drug Evaluations Annual, 1994, p2290)
A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)
A topical glucocorticoid used in various DERMATOSES. It is absorbed through the skin, bound to plasma albumin, and may cause adrenal suppression. It is also administered as the valerate.
A difluorophenyl derivate of salicylic acid and a nonsteroidal anti-inflammatory drug (NSAID) with antipyretic, analgesic and anti-inflammatory properties. Diflunisal competitively inhibits both cyclooxygenase (COX) -1 and -2, with higher affinity for COX-1, and subsequently blocks the conversion of arachidonic acid to prostaglandin precursors. This leads to an inhibition of the formation of prostaglandins that are involved in pain, inflammation and fever. Diflunisal differs from other salicylates, in that it is not metabolized to salicylic acid, hence it has a longer half-life.
Individuals with 22q11.2 deletion syndrome (22q11.2DS) have a range of findings including the following: Congenital heart disease (74% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus). Palatal abnormalities (69%), particularly velopharyngeal incompetence, submucosal cleft palate, bifid uvula, and cleft palate. Characteristic facial features (present in the majority of individuals of northern European heritage). Learning difficulties (70%-90%). An immune deficiency (regardless of the clinical presentation) (77%). Additional findings include the following: Hypocalcemia (50%). Significant feeding and swallowing problems; constipation with or without structural gastrointestinal anomalies (intestinal malrotation, imperforate anus, and Hirschsprung disease). Renal anomalies (31%). Hearing loss (both conductive and sensorineural). Laryngotracheoesophageal anomalies. Growth hormone deficiency. Autoimmune disorders. Seizures (idiopathic or associated with hypocalcemia). CNS anomalies including tethered cord. Skeletal abnormalities (scoliosis with or without vertebral anomalies, clubbed feet, polydactyly, and craniosynostosis). Ophthalmologic abnormalities (strabismus, posterior embryotoxon, tortuous retinal vessels, scleracornea, and anophthalmia). Enamel hypoplasia. Malignancies (rare). Developmental delay (in particular delays in emergence of language), intellectual disability, and learning differences (non-verbal learning disability where the verbal IQ is significantly greater than the performance IQ) are common. Autism or autistic spectrum disorder is found in approximately 20% of children and psychiatric illness (specifically schizophrenia) is present in 25% of adults; however, attention deficit disorder, anxiety, perseveration, and difficulty with social interactions are also common.
An agent that favors or assists the process of digestion.
An abnormality of the gastrointestinal tract.
Tumors or cancer of the DIGESTIVE SYSTEM.
Glycosides from plants of the genus DIGITALIS. Some of these are useful as cardiotonic and anti-arrhythmia agents. Included also are semi-synthetic derivatives of the naturally occurring glycosides. The term has sometimes been used more broadly to include all CARDIAC GLYCOSIDES, but here is restricted to those related to Digitalis.
3 beta,14-Dihydroxy-5 beta-card-20(22)enolide. A cardenolide which is the aglycon of digitoxin. Synonyms: Cerberigenin; Echujetin; Evonogenin; Thevetigenin.
A cardiac glycoside sometimes used in place of DIGOXIN. It has a longer half-life than digoxin; toxic effects, which are similar to those of digoxin, are longer lasting. (From Martindale, The Extra Pharmacopoeia, 30th ed, p665)
3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh.
A cardiac glycoside. Digoxin inhibits the sodium potassium adenosine triphosphatase (ATPase) pump, thereby increasing intracellular calcium and enhancing cardiac contractility. This agent also acts directly on the atrioventricular node to suppress conduction, thereby slowing conduction velocity. Apparently due to its effects on intracellular calcium concentrations, digoxin induces apoptosis of tumor cells via a pathway involving mitochondrial cytochrome c and caspases 8 and 3. (NCI04)
1,4-Dihydrazinophthalazine. An antihypertensive agent with actions and uses similar to those of HYDRALAZINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p354)
Dihydro analog of beta-erythroidine, which is isolated from the seeds and other plant parts of Erythrina sp. Leguminosae. It is an alkaloid with curarimimetic properties.
Hydrogenated alprenolol derivative where the extra hydrogens are often tritiated. This radiolabeled form of ALPRENOLOL, a beta-adrenergic blocker, is used to label the beta-adrenergic receptor for isolation and study.
A 9,10alpha-dihydro derivative of ERGOTAMINE that contains isopropyl sidechains at the 2' and 5' positions of the molecule.
A 9,10alpha-dihydro derivative of ERGOTAMINE that contains an isopropyl sidechain at the 2' position of the molecule.
A 9,10alpha-dihydro derivative of ERGOTAMINE that contains an isopropyl sidechain at the 2' position and an alpha-isobutyl sidechain at 5'alpha position of the molecule.
A 9,10alpha-dihydro derivative of ERGOTAMINE. It is used as a vasoconstrictor, specifically for the therapy of MIGRAINE DISORDERS.
A mixture of three different hydrogenated derivatives of ERGOTAMINE: DIHYDROERGOCORNINE; DIHYDROERGOCRISTINE; and DIHYDROERGOCRYPTINE. Dihydroergotoxine has been proposed to be a neuroprotective agent and a nootropic agent. The mechanism of its therapeutic actions is not clear, but it can act as an alpha-adrenergic antagonist and a dopamine agonist. The methanesulfonate salts of this mixture of alkaloids are called ERGOLOID MESYLATES.
A semisynthetic analgesic used in the study of narcotic receptors.
An opioid analgesic made from MORPHINE and used mainly as an analgesic. It has a shorter duration of action than morphine.
Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.
A VITAMIN D that can be regarded as a reduction product of vitamin D2.
A ketotriose compound. Its addition to blood preservation solutions results in better maintenance of 2,3-diphosphoglycerate levels during storage. It is readily phosphorylated to dihydroxyacetone phosphate by triokinase in erythrocytes. In combination with naphthoquinones it acts as a sunscreening agent.
Cholecalciferols substituted with two hydroxy groups in any position.
Tryptamine substituted with two hydroxyl groups in any position. Some are cytotoxic serotonin analogs that are preferentially taken up by serotonergic neurons and then destroy those neurons.
One of the halogenated 8-quinolinols widely used as an intestinal antiseptic, especially as an antiamebic agent. It is also used topically in other infections and may cause CNS and eye damage. It is known by very many similar trade names world-wide.
A pathophysiological process characterized by the dilatation or expansion of a hollow, tubular tissue or organ.
Coronary vasodilator with some antiarrhythmic activity.
A benzothiazepine derivative with anti-hypertensive, antiarrhythmic properties. Diltiazem blocks voltage-sensitive calcium channels in the blood vessels, by inhibiting the ion-control gating mechanisms, thereby preventing calcium levels increase by other revenues. Alternatively, it has been suggested that this agent also interferes with the release of calcium from the sarcoplasmic reticulum and inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The overall low calcium levels leads to dilatation of the main coronary and systemic arteries and decreasing myocardial contractility, decreased peripheral arterial resistance, improved oxygen delivery to the myocardial tissue, and decreased cardiac output.
A drug combination that contains diphenhydramine and theophylline. It is used for treating VERTIGO, MOTION SICKNESS, and NAUSEA associated with PREGNANCY.
A metal chelating agent that is used as an antidote in arsenic, gold, lead, mercury and other heavy metal poisoning. Metals form ligands in the body with the sulfhydryl groups of the pyruvate-oxidase enzyme system. This leads to an inhibition of the normal functioning of these enzymes that are dependent on free sulfhydryl groups for their activity. Dimercaprol reverses the enzyme inhibition by chelating the metal and regenerates free sulfhydryl groups, thereby preventing and reversing the metals toxic effects.
A mercaptodicarboxylic acid used as an antidote to heavy metal poisoning because it forms strong chelates with them.
An anticonvulsant that is the active metabolite of TRIMETHADIONE.
A histamine H1 antagonist. It is used in hypersensitivity reactions, in rhinitis, for pruritus, and in some common cold remedies.
A synthetic progestational hormone without significant estrogenic or androgenic properties. It was formerly used as the progestational component in oral sequential contraceptives.
A highly polar organic liquid that is used widely as a chemical solvent and a free radical scavenger. It shows a range of pharmacological activity including analgesia and anti-inflammation. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect cells and tissue during cryopreservation and has been used to treat extravasation damage caused by anthracycline-based chemotherapy.
A chemical that acts as a dopamine beta-hydroxylase inhibitor. Its salts are agricultural fungicides. It is inferior to diethyldithiocarbamate as a chelating agent.
A compound used to treat histomoniasis in poultry.
An insect growth regulator which interferes with the formation of the insect cuticle. It is effective in the control of mosquitoes and flies.
A myristoylated phosphatidylcholine, and a synthetic phospholipid used in liposomes and lipid bilayers with drug delivery property.
A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.
A synthetic prostaglandin E2 (PGE2) analogue with smooth muscle contraction inducing property. It has been suggested that PGE2 regulates the intracellular levels of cyclic 3, 5-adenosine monophosphate (cAMP) by activating adenylate cyclase and thereby increases cellular membrane calcium ion transport. By acting directly on the myometrium, dinoprostone induces uterine and gastrointestinal smooth muscle contractions.
All-purpose surfactant, wetting agent, and solubilizer used in the drug, cosmetics, and food industries. It has also been used in laxatives and as cerumenolytics. It is usually administered as either the calcium, potassium, or sodium salt.
A bioflavonoid that strengthens vascular walls.
A parasitic infection caused by genus of filarial worms called Dipetalonema. It produces microfilariae in the blood and body fluids.
A first generation antihistamine and ethanolamine with sedative and anti-allergic properties. Diphenhydramine competitively inhibits the histamine-1 (H1) receptor, thereby alleviating the symptoms caused by endogenous histamine on bronchial, capillary and gastrointestinal smooth muscles. This prevents histamine-induced bronchoconstriction, vasodilation, increased capillary permeability, and GI smooth muscle spasms.
A MEPERIDINE congener used as an antidiarrheal, usually in combination with ATROPINE. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity.
In humans it may be irritating to mucous membranes. Methemoglobinemia has been produced experimentally. In veterinary use, it is one of active ingredients in topical agents for prevention and treatment of screwworm infestation. An indicator in tests for nitrate poisoning.
Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.
A Gram-positive bacterial infection caused by Corynebacterium diphtheriae. It usually involves the oral cavity, pharynx, and nasal cavity. Patients develop pseudomembranes in the affected areas and manifest signs and symptoms of an upper respiratory infection. The diphtheria toxin may cause myocarditis, polyneuritis, and other systemic effects.
An antitoxin produced against the toxin of CORYNEBACTERIUM DIPHTHERIAE that is used for the treatment of DIPHTHERIA.
The formaldehyde-inactivated toxin of Corynebacterium diphtheriae. It is generally used in mixtures with TETANUS TOXOID and PERTUSSIS VACCINE; (DTP); or with tetanus toxoid alone (DT for pediatric use and Td, which contains 5- to 10-fold less diphtheria toxoid, for other use). Diphtheria toxoid is used for the prevention of diphtheria; DIPHTHERIA ANTITOXIN is for treatment.
Infection of the anterior nasal structures by Corynebacterium diphtheriae.
Pseudomembranous colitis resulting from infection by Corynebacterium diphtheriae.
A usually mild form of diphtheria characterized by infection of the skin by corynebacterium diphtheria and the resulting formation of a chronic, shallow ulcer that is sometimes bordered or followed by a bulla.
Infection of the fauces by Corynebacterium diphtheriae.
Infection of the larynx by Corynebacterium diphtheriae.
Infection of the nasopharynx by Corynebacterium diphtheriae.
An infection that is caused by the tapeworm Diphyllobothrium latum and related species; it is transmitted via consumption of raw or undercooked fish, and symptoms include abdominal discomfort, diarrhea, vomiting, fatigue, weight loss, and vitamin B12 deficiency.
A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include REFRACTIVE ERRORS; STRABISMUS; OCULOMOTOR NERVE DISEASES; TROCHLEAR NERVE DISEASES; ABDUCENS NERVE DISEASES; and diseases of the BRAIN STEM and OCCIPITAL LOBE.
A narcotic antagonist similar in action to NALOXONE. It is used to remobilize animals after ETORPHINE neuroleptanalgesia and is considered a specific antagonist to etorphine.
A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)
A drug that has analgesic, anti-inflammatory, and antipyretic properties. It is the sodium sulfonate of AMINOPYRINE.
Infection with nematodes of the genus DIROFILARIA, usually in animals, especially dogs, but occasionally in man.
Inflammation of an INTERVERTEBRAL DISC or disk space which may lead to disk erosion. Until recently, discitis has been defined as a nonbacterial inflammation and has been attributed to aseptic processes (e.g., chemical reaction to an injected substance). However, recent studies provide evidence that infection may be the initial cause, but perhaps not the promoter, of most cases of discitis. Discitis has been diagnosed in patients following discography, myelography, lumbar puncture, paravertebral injection, and obstetrical epidural anesthesia. Discitis following chemonucleolysis (especially with chymopapain) is attributed to chemical reaction by some and to introduction of microorganisms by others.
A type of constriction that is caused by the presence of a fibrous ring (discrete type) below the AORTIC VALVE, anywhere between the aortic valve and the MITRAL VALVE. It is characterized by restricted outflow from the LEFT VENTRICLE into the AORTA.
A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.
Disorders affecting TWINS, one or both, at any age.
A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.
The disodium salt form of edetate, a heavy metal chelating agent with anti-hypercalcemic and anti-arrhythmic properties. Edetate, a heavy metal antagonist, chelates divalent and trivalent metals, forming soluble stable complexes which are readily excreted by the kidneys, thereby can be used to lower serum calcium concentrations. In addition, this agent exerts a negative inotropic effect on the heart through a transiently induced hypocalcemic state, thereby antagonizing the inotropic and chronotropic effects of digitalis glycosides on the ventricles of the heart. Upon ocular administration, edetate exerts its ophthalmic effect by chelating calcium to form soluble complexes, thereby removing corneal calcium deposits.
A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.
Disorders in the processing of iron in the body: its absorption, transport, storage, and utilization. (From Mosby's Medical, Nursing, & Allied Health Dictionary, 4th ed)
A classification of disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM) that are usually diagnosed in infancy, childhood or adolescence and are characterized by an individual's inability to behave in a cooperative manner.
A dissecting aneurysm formed between the intimal and medial layers of the aortic wall due to a tear in the tunica intima.
A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.
A category of psychiatric disorders which are characterized by a disruption in the usually integrated functions of consciousness, memory, identity, and/or perception of the environment.
A name for several highly contagious viral diseases of animals, especially canine distemper. In dogs, it is caused by the canine distemper virus (DISTEMPER VIRUS, CANINE). It is characterized by a diphasic fever, leukopenia, gastrointestinal and respiratory inflammation and sometimes, neurologic complications. In cats it is known as FELINE PANLEUKOPENIA.
Disruption of the normal functioning of the sensory nerves in the skin.
A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.
3-Ethyl-2-(5-(3-ethyl-2-benzothiazolinylidene)-1,3- pentadienyl)benzothiazolium. A benzothiazole that was formerly used as an antinematodal agent and is currently used as a fluorescent dye.
A reagent commonly used in biochemical studies as a protective agent to prevent the oxidation of SH (thiol) groups and for reducing disulphides to dithiols.
Chelating agent used for heavy metal poisoning and assay. It causes diabetes.
The chloride salt form of succinylcholine, a quaternary ammonium compound and depolarizing agent with short-term muscle relaxant properties. Succinylcholine chloride binds to nicotinic receptors at the neuromuscular junction and opening the ligand-gated channels in the same way as acetylcholine, resulting in depolarization and inhibition of neuromuscular transmission. Depolarization may be prolonged due to succinylcholine's resistance to acetylcholinesterases thereby leading to disorganized muscle contraction followed by skeletal muscle relaxation and flaccid paralysis.
A class of agents that increases the production of urine by the kidney. Via various mechanism of actions, diuretics retain water in urine, thus provides a means of forced diuresis.
Compounds that increase urine volume by increasing the amount of osmotically active solute in the urine. Osmotic diuretics also increase the osmolarity of plasma.
Any benzothiadiazide derivative or other thiazide-like agent with diuretic and anti-hypertensive activity. Thiazide diuretics inhibit the sodium-chloride transporter in the distal tubule in the kidneys, thereby suppressing sodium and chloride reabsorption from the distal convoluted tubules (DCT) and increasing the excretion of sodium, chloride, potassium and water. In addition, thiazide diuretics decrease excretion of calcium and uric acid. These agents cause vasodilation possibly by activating calcium-activated potassium channels in vascular smooth muscle and inhibiting various carbonic anhydrases in vascular tissue.
The presence of multiple diverticula of the colon.
An infection that develops in the diverticula of the intestinal tract. Signs and symptoms include abdominal pain, fever, and leukocytosis.
Inflammation of the COLONIC DIVERTICULA, generally with abscess formation and subsequent perforation.
A pouch formed at a weakened area of wall in a hollow organ structure.
A pathological condition characterized by the presence of a number of COLONIC DIVERTICULA in the COLON. Its pathogenesis is multifactorial, including colon aging, motor dysfunction, increases in intraluminal pressure, and lack of dietary fibers.
A sensation of lightheadedness, unsteadiness, turning, spinning or rocking.
A selective nicotinic cholinergic agonist used as a research tool. DMPP activates nicotinic receptors in autonomic ganglia but has little effect at the neuromuscular junction.
Drug-, radiation-induced, or spontaneous injuries to DNA that introduce deviations from its normal double-helical conformation. These changes include structural distortions that interfere with replication and transcription, as well as point mutations that disrupt base pairs and exert damaging effects on future generations through changes in DNA sequence. If the damage is minor, it can often be repaired (DNA repair); extensive damage can induce apoptosis.
A catecholamine derivative with specificity for BETA-1 ADRENERGIC RECEPTORS. It is commonly used as a cardiotonic agent after CARDIAC SURGERY and during DOBUTAMINE STRESS ECHOCARDIOGRAPHY.
C22-unsaturated fatty acids found predominantly in FISH OILS.
Diseases of the domestic dog (Canis familiaris). This term does not include diseases of wild dogs, WOLVES; FOXES; and other Canidae for which the heading CARNIVORA is used.
A peripheral-specific antagonist of the dopamine receptor D2 (D2R), with antiemetic, gastrokinetic and galactagogue activities. Following administration, domperidone binds to D2R expressed by peripheral neurons; this inhibits dopamine binding and D2R-mediated signaling. Inhibition of peripheral D2R signaling prevents or relieves various gastrointestinal (GI) symptoms, such as nausea and vomiting, and may help relief reflux and symptoms of a variety of other upper GI disorders.
A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.
A monoamine compound with positive inotropic activity. Dopamine is a naturally occurring catecholamine formed by decarboxylation of dehydroxyphenylalanine and a precursor of norepinephrine and epinephrine. Dopamine binds to alpha-1 and beta-1 adrenergic receptors. Mediated through myocardial beta-1 adrenergic receptors, dopamine increase heart rate and force, thereby increasing cardiac output. Alpha-1 adrenergic receptor stimulation on vascular smooth muscle, leads to vasoconstriction and results in an increase in systemic vascular resistance. Stimulation of dopaminergic receptors in renal vasculature, leads to renal blood vessel dilation, and an increase in glomerular filtration rate, renal blood flow, sodium excretion, and urine output.
Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.
A tricyclic antidepressant with some tranquilizing action.
A rare congenital cardiovascular abnormality in which both the aorta and the pulmonary artery arise from the right ventricle.
A disease of horses and donkeys caused by Trypanosoma equiperdum. The disease occurs in Africa, the Americas, and Asia.
Down syndrome, the most frequent form of mental retardation caused by a microscopically demonstrable chromosomal aberration, is characterized by well-defined and distinctive phenotypic features and natural history. It is caused by triplicate state (trisomy) of all or a critical portion of chromosome 21.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A central respiratory stimulant with a brief duration of action. (From Martindale, The Extra Pharmocopoeia, 30th ed, p1225)
A dibenzoxepin derivative and tricyclic antidepressant (TCA) with antipruritic, antidepressive and anxiolytic activities. Doxepin blocks the reuptake of norepinephrine and serotonin (5-HT) into presynaptic terminals thereby prolonging the availability of the monoaminergic neurotransmitters within the synaptic cleft and enhancing their neurotransmission. Doxepin also has antagonistic effects on histamine H1, 5-HT2, alpha-1 adrenergic, and muscarinic receptors. The antipruritic effect of this agent is mediated through inhibition of histamine receptors.
A first generation ethanolamine with antiinflammatory, sedative and antihistamine properties. Doxylamine competitively inhibits the histamine 1 (H1) receptor, thereby preventing the action of endogenous histamine as well as the subsequent release of pro-inflammatory mediators from basophils and mast cells. This agent acts as an inverse agonist that combines with, and stabilizes the inactive form of the H1-receptor, shifting the H1 receptor equilibrium toward the inactive state. This results in downregulation of nuclear factor-kappaB (NF-kappaB) and NF-kappaB dependent antigen presentation, chemotaxis, as well as expression of cell-adhesion molecules and pro-inflammatory cytokines.
A parasitic infection caused by Dracunculus medinensis. It is caused by drinking water contaminated with water fleas. The larvae enter the body through the intestine. Signs and symptoms include pain, edema, blisters, and ulcers.
Habitual flow of saliva out of the mouth.
A butyrophenone with anti-emetic, sedative and anti-anxiety properties. Although the exact mechanism through which droperidol exerts its effects is unknown, droperidol may block dopamine receptors in the chemoreceptor trigger zone (CTZ), which may lead to its anti-emetic effect. This agent may also bind to postsynaptic gamma-aminobutyric acid (GABA) receptors in the central nervous system (CNS), which increases the inhibitory effect of GABA and leads to sedative and anti-anxiety activities.
The use of a drug for a reason other than which it was intended or in a manner or in quantities other than directed.
Phenomena and pharmaceutics of compounds that inhibit the function of agonists (DRUG AGONISM) and inverse agonists (DRUG INVERSE AGONISM) for a specific receptor. On their own, antagonists produce no effect by themselves to a receptor, and are said to have neither intrinsic activity nor efficacy.
Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture.
process whereby an individual's response to a drug lessens with repeated use.
Immunologically mediated adverse reactions to medicinal substances used legally or illegally.
The action of a drug in promoting or enhancing the effectiveness of another drug.
A reduction in the sensitivity to a drug following its repeated administration, in which increased doses are required to produce the same magnitude of effect previously produced by a smaller dose. This increase in dose may be necessitated by changes in the metabolism of the drug, or a cellular, physiological or behavioral adaptation to the effects of the drug.
A drug product that contains one or more active and/or inactive ingredients; it is intended to treat, prevent or alleviate the symptoms of disease. This term does not refer to the individual ingredients that make up the product.
Chinese herbal or plant extracts which are used as drugs to treat diseases or promote general well-being. The concept does not include synthesized compounds manufactured in China.
A new drug or biological drug that is used in a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes.
A medicine or device that can be bought without a doctor's order or prescription.
A compound or product that demonstrates promise for the diagnosis and/or treatment of rare diseases and conditions that affect fewer than 200,000 people. The U.S. Orphan Drug Act (1983) encourages development of these therapeutics by tax breaks and a seven-year monopoly on drug sales. These incentives promote the development and manufacturing of such therapeutics, which otherwise might not be profitable because of the small potential market.
A syndrome characterized by dryness of the cornea and conjunctiva. It is usually caused by a deficiency in tear production. Symptoms include a feeling of burning eyes and a possible foreign body presence in the eye.
A condition sometimes occurring after tooth extraction, particularly after traumatic extraction, resulting in a dry appearance of the exposed bone in the socket, due to disintegration or loss of the blood clot. It is basically a focal osteomyelitis without suppuration and is accompanied by severe pain (alveolalgia) and foul odor. (Dorland, 28th ed)
An edetate and a chelating agent used in preparing radiopharmaceuticals. Pentetic acid (DTPA) has strong affinity for iron but also shows affinities for other heavy metals, thereby is used in the treatment of iron-storage disease and poisoning from heavy and radioactive metals. DTPA may chelate metallic moieties of unbound, extracellular radioimmunotherapeutics, thereby aggregating radioimmunotherapeutics locally to higher concentrations, and improving tumor cell radiocytotoxicity, while sparing normal tissues from the radiocytotoxic effects. In addition, DTPA is used in radioimaing procedures when complexes with radioisotopes, ex., Tc 99m or In 111.
Duane syndrome is a strabismus syndrome characterized by congenital non-progressive horizontal ophthalmoplegia (inability to move the eyes) primarily affecting the abducens nucleus and nerve and its innervated extraocular muscle, the lateral rectus muscle. At birth, affected infants have restricted ability to move the affected eye(s) outward (abduction) and/or inward (adduction). In addition, the globe retracts into the orbit with attempted adduction, accompanied by narrowing of the palpebral fissure. Most individuals with Duane syndrome have strabismus in primary gaze but can use a compensatory head position to align the eyes, and thus can preserve single binocular vision and avoid diplopia. Individuals with Duane syndrome who lack binocular vision are at risk for amblyopia. Approximately 70% of individuals with Duane syndrome have isolated Duane syndrome (i.e., they do not have other detected congenital anomalies).
The dystrophinopathies cover a spectrum of X-linked muscle disease ranging from mild to severe that includes Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy (DCM). The mild end of the spectrum includes the phenotypes of asymptomatic increase in serum concentration of creatine phosphokinase (CK) and muscle cramps with myoglobinuria. The severe end of the spectrum includes progressive muscle diseases that are classified as Duchenne/Becker muscular dystrophy when skeletal muscle is primarily affected and as DMD-associated dilated cardiomyopathy (DCM) when the heart is primarily affected. Duchenne muscular dystrophy (DMD) usually presents in early childhood with delayed motor milestones including delays in walking independently and standing up from a supine position. Proximal weakness causes a waddling gait and difficulty climbing stairs, running, jumping, and standing up from a squatting position. DMD is rapidly progressive, with affected children being wheelchair dependent by age 12 years. Cardiomyopathy occurs in almost all individuals with DMD after age 18 years. Few survive beyond the third decade, with respiratory complications and progressive cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness. With improved diagnostic techniques, it has been recognized that the mild end of the spectrum includes men with onset of symptoms after age 30 years who remain ambulatory even into their 60s. Despite the milder skeletal muscle involvement, heart failure from DCM is a common cause of morbidity and the most common cause of death in BMD. Mean age of death is in the mid-40s. DMD-associated DCM is characterized by left ventricular dilation and congestive heart failure. Females heterozygous for a DMD pathogenic variant are at increased risk for DCM.
A congenital defect characterized by the failure of the ductus arteriosus to close soon after birth. As a consequence, blood from the aorta mixes with blood from the pulmonary artery. If untreated, it may lead to congestive heart failure.
A disorder of the gastrointestinal tract. It is typically caused by the rapid emptying of undigested food from the stomach to the small intestine following gastroesophageal surgery but may be seen secondary to diabetes or the use of certain medications. Clinical signs may be seen 30-60 minutes after eating (early dumping): cramping, nausea, vomiting and diarrhea or they may be seen 1-3 hours later as a result of hyperinsulinemic hypoglycemia (late dumping): sweating, dizziness, confusion and heart palpitations. Untreated, the clinical course progresses to malnutrition and weight loss.
Pathological conditions in the DUODENUM region of the small intestine (INTESTINE, SMALL).
A benign or malignant neoplasm that affects the wall of the duodenum. Representative examples include adenoma, carcinoma, and lymphoma.
Blockage of the normal flow of stomach contents through the duodenum.
Acute or chronic inflammation of the duodenum. Causes include bacterial and viral infections and gastroesophageal reflux disease. Symptoms include vomiting and abdominal pain.
Retrograde flow of duodenal contents (BILE ACIDS; PANCREATIC JUICE) into the STOMACH.
Dupuytren contracture is the most common heritable disorder of connective tissue. It is a disease of the soft tissues of the palm and fingers characterized by a progressive thickening and shortening of the fascial structures that normally provide support to the glabrous skin of the palm. Although it can also be a sporadic disorder, the inherited form is most frequently observed among people of Nordic descent. There is a male: female ratio of greater than 3:1 (Hu et al., 2005). Dupuytren contracture has been associated with multiple fibroproliferative conditions, including Peyronie disease (171000), knuckle pads (149100), congenital generalized fibromatosis (228550), juvenile fibromatosis (228600), and frozen shoulder, suggesting a common underlying defect in wound repair (Hu et al., 2005).
A genetic or pathological condition that is characterized by short stature and undersize. Abnormal skeletal growth usually results in an adult who is significantly below the average height.
A form of dwarfism caused by complete or partial GROWTH HORMONE deficiency, resulting from either the lack of GROWTH HORMONE-RELEASING FACTOR from the HYPOTHALAMUS or from the mutations in the growth hormone gene (GH1) in the PITUITARY GLAND. It is also known as Type I pituitary dwarfism. Human hypophysial dwarf is caused by a deficiency of HUMAN GROWTH HORMONE during development.
A synthetic progestational hormone with no androgenic or estrogenic properties. Unlike many other progestational compounds, dydrogesterone produces no increase in temperature and does not inhibit OVULATION.
A THEOPHYLLINE derivative with broncho- and vasodilator properties. It is used in the treatment of asthma, cardiac dyspnea, and bronchitis.
Disorders of speech articulation caused by imperfect coordination of pharynx, larynx, tongue, or face muscles. This may result from CRANIAL NERVE DISEASES; NEUROMUSCULAR DISEASES; CEREBELLAR DISEASES; BASAL GANGLIA DISEASES; BRAIN STEM diseases; or diseases of the corticobulbar tracts (see PYRAMIDAL TRACTS). The cortical language centers are intact in this condition. (From Adams et al., Principles of Neurology, 6th ed, p489)
An acute or chronic disorder, affecting the sympathetic or parasympathetic nervous system. It can be primary, the result of central nervous system degeneration, or secondary due to diabetes or alcoholism. Patients with the chronic form of this disorder usually have a progressive clinical course and a poor prognosis.
Familial dysautonomia (FD) affects the development and survival of sensory, sympathetic, and parasympathetic neurons. It is a debilitating disease present from birth. Neuronal degeneration progresses throughout life. Affected individuals have gastrointestinal dysfunction, vomiting crises, recurrent pneumonia, altered sensitivity to pain and temperature perception, and cardiovascular instability. About 40% of individuals have autonomic crises. Hypotonia contributes to delay in acquisition of motor milestones. Older individuals often have a broad-based and ataxic gait that deteriorates over time. Life expectancy is decreased.
Acute inflammation of the intestine associated with infectious DIARRHEA of various etiologies, generally acquired by eating contaminated food containing TOXINS, BIOLOGICAL derived from BACTERIA or other microorganisms. Dysentery is characterized initially by watery FECES then by bloody mucoid stools. It is often associated with ABDOMINAL PAIN; FEVER; and DEHYDRATION.
Colitis resulting from amebic infection.
An immunologic deficiency state characterized by selective deficiencies of one or more, but not all, classes of immunoglobulins.
A malignant germ cell tumor characterized by the presence of a monotonous primitive germ cell population. The neoplastic cells form aggregates and have an abundant pale cytoplasm and uniform nuclei. The aggregates of the germ cells are separated by fibrous septa which contain inflammatory cells, mostly T-lymphocytes. It arises primarily in the ovaries, but can occur both primarily and secondarily at other sites, particularly the central nervous system. It responds to chemotherapy and radiotherapy. Its prognosis is related to the tumor stage.
A condition characterized by alterations of the sense of taste which may range from mild to severe, including gross distortions of taste quality.
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Abnormal movements, including HYPERKINESIS; HYPOKINESIA; TREMOR; and DYSTONIA, associated with the use of certain medications or drugs. Muscles of the face, trunk, neck, and extremities are most commonly affected. Tardive dyskinesia refers to abnormal hyperkinetic movements of the muscles of the face, tongue, and neck associated with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS). (Adams et al., Principles of Neurology, 6th ed, p1199)
A receptive visual aphasia characterized by the loss of a previously possessed ability to comprehend the meaning or significance of handwritten words, despite intact vision. This condition may be associated with posterior cerebral artery infarction (INFARCTION, POSTERIOR CEREBRAL ARTERY) and other BRAIN DISEASES.
Abnormally painful abdominal cramps during menstruation.
An uncomfortable, often painful feeling in the stomach, resulting from impaired digestion. Symptoms include burning stomach pain, bloating, heartburn, nausea, and vomiting. Causes include gastritis, gastric ulcer, gastroesophageal reflux disease, pancreatic disease, and gallbladder disease.
An autosomal dominant disorder defined by the presence of multiple dysplastic nevi and a history of melanoma in two family members. Patients are at an increased risk for the development of melanoma.
A disorder characterized by sudden attacks of respiratory distress in at rest patients with HEART FAILURE and PULMONARY EDEMA. It usually occurs at night after several hours of sleep in a reclining position. Patients awaken with a feeling of suffocation, coughing, a cold sweat, and TACHYCARDIA. When there is significant WHEEZING, it is called cardiac asthma.
A chronic mood disorder in which the symptoms are similar to, though milder than, those diagnosed in depression.
Slow or difficult OBSTETRIC LABOR or CHILDBIRTH.
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
A condition characterized by focal DYSTONIA that progresses to involuntary spasmodic contractions of the muscles of the legs, trunk, arms, and face. The hands are often spared, however, sustained axial and limb contractions may lead to a state where the body is grossly contorted. Onset is usually in the first or second decade. Familial patterns of inheritance, primarily autosomal dominant with incomplete penetrance, have been identified. (Adams et al., Principles of Neurology, 6th ed, p1078)
A non-neoplastic lesion that affects the vulva and is characterized by thinning or thickening of the skin and dryness.
A non-neoplastic or neoplastic disorder that affects the ear. Representative examples include infections, hearing disorders, benign neoplasms, and carcinomas.
A benign or malignant neoplasm that affects the external, middle, or internal ear. Representative examples include ceruminous adenoma, polyp, and carcinoma.
Pain in the ear can be a consequence of otologic disease (primary or otogenic otalgia), or can arise from pathologic processes and structures other than the ear (secondary or referred otalgia).
A broad group of psychological disorders with abnormal eating behaviors leading to physiological effects from overeating or insufficient food intake.
Ebstein anomaly is characterized by downward displacement of variable severity of the tricuspid valve into the right ventricle. The valve leaflets may be dysplastic, and a variable portion of the proximal part of the right ventricle is in continuity with the right atrium ('atrialized'), because of the abnormally positioned tricuspid valve. The severity of this defect includes a spectrum ranging from severe disturbance in fetal and neonatal life to virtually asymptomatic survival to adult life. Associated extracardiac anomalies in the setting of chromosomal or mendelian disorders occur in about 20% of patients with Ebstein anomaly. Nonsyndromic Ebstein anomaly can occur as a sporadic or a familial defect (summary by Digilio et al., 2011).
A flat discoloration of the skin or a mucous membrane, larger in area than a petechia, caused by the extravasation of blood.
A parasitic infection caused by tapeworm larvae of Echinococcus. It affects livestock and humans. It is characterized by the formation of hydatid cysts mainly in the liver, lungs, spleen, and kidneys. Rupture of the cysts may lead to shock.
Liver disease caused by infections with parasitic tapeworms of the genus ECHINOCOCCUS, such as Echinococcus granulosus or Echinococcus multilocularis. Ingested Echinococcus ova burrow into the intestinal mucosa. The larval migration to the liver via the PORTAL VEIN leads to watery vesicles (HYDATID CYST).
Helminth infection of the lung caused by Echinococcus granulosus or Echinococcus multilocularis.
Infection by flukes of the genus Echinostoma.
A symptom of neurologic or psychiatric dysfunction in which the individual involuntarily and meaninglessly repeats a recently heard word, series of words, or a song.
A potent, long-acting cholinesterase inhibitor used as a miotic in the treatment of glaucoma.
Infectious disease processes, including meningitis, diarrhea, and respiratory disorders, caused by echoviruses.
A potentially life-threatening pregnancy-related disorder characterized by tonic-clonic seizures in association with hypertension after the twentieth week of gestation and up to six weeks postpartum and in the absence of other potential causes of seizures.
An imidazole derivative that is commonly used as a topical antifungal agent.
An ulcerative pyoderma usually caused by group A beta-hemolytic streptococcal infection at the site of minor trauma. (Dorland, 27th ed)
An infectious dermatitis of sheep and goats, affecting primarily the muzzle and lips. It is caused by a poxvirus and may be transmitted to man.
A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, FOCAL DERMAL HYPOPLASIA, and aplasia cutis congenita.
Infestations by PARASITES which live on, or burrow into, the surface of their host's EPIDERMIS. Most ectoparasites are ARTHROPODS.
A rare congenital anomaly where the heart is formed outside of the thoracic cavity. It is associated with intracardiac lesions and other structural malformations.
Congenital displacement of the lens resulting from defective zonule formation.
A congenital defect characterized by the absence or hypoplasia of one or more extremities.
A viral infection of mice, causing edema and necrosis followed by limb loss.
An outward turning (eversion) or rotation of the eyelid margin.
A form of dermatitis characterized by red, itchy, scaly, or crusty patches that can be chronic or intermittent.
Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.
An acute disease of young pigs that is usually associated with weaning. It is characterized clinically by paresis and subcutaneous edema.
Abnormal fluid retention by the body due to impaired cardiac function or heart failure. It is usually characterized by increase in venous and capillary pressure, and swollen legs when standing. It is different from the generalized edema caused by renal dysfunction (NEPHROTIC SYNDROME).
Swelling due to an excessive accumulation of fluid at a specific anatomic site.
A rapid-onset, short-acting cholinesterase inhibitor used in cardiac arrhythmias and in the diagnosis of myasthenia gravis. It has also been used as an antidote to curare principles.
The chloride salt form of edrophonium, a short and rapid-acting cholinesterase inhibitor with parasympathomimetic activity. Echothiophate chloride potentiates the action of endogenous acetylcholine by inhibiting acetylcholinesterase that hydrolyzes acetylcholine. When applied topically to the eye, this agent prolongs stimulation of the parasympathetic receptors at the neuromuscular junctions of the longitudinal muscle of the ciliary body. Contraction of longitudinal muscle pulls on the scleral spur, and opens the trabecular meshwork, thereby increases aqueous humor outflow from the eye and reduces intraocular pressure.
A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.
An indication of the years of schooling completed in graded public, private, or parochial schools, and in colleges, universities, or professional schools.
A collection of fluid in a body cavity, which may be the result of a non-neoplastic disorder (e.g. heart failure) or a tumor (e.g. carcinoma of the lung).
Ehlers-Danlos syndrome is a group of disorders that affect connective tissues supporting the skin, bones, blood vessels, and many other organs and tissues. Defects in connective tissues cause the signs and symptoms of these conditions, which range from mildly loose joints to life-threatening complications.The various forms of Ehlers-Danlos syndrome have been classified in several different ways. Originally, 11 forms of Ehlers-Danlos syndrome were named using Roman numerals to indicate the types (type I, type II, and so on). In 1997, researchers proposed a simpler classification (the Villefranche nomenclature) that reduced the number of types to six and gave them descriptive names based on their major features. In 2017, the classification was updated to include rare forms of Ehlers-Danlos syndrome that were discovered more recently. The 2017 classification describes 13 types of Ehlers-Danlos syndrome.An unusually large range of joint movement (hypermobility) occurs in most forms of Ehlers-Danlos syndrome, and it is a hallmark feature of the hypermobile type. Infants and children with hypermobility often have weak muscle tone (hypotonia), which can delay the development of motor skills such as sitting, standing, and walking. The loose joints are unstable and prone to dislocation and chronic pain. In the arthrochalasia type of Ehlers-Danlos syndrome, infants have hypermobility and dislocations of both hips at birth.Many people with the Ehlers-Danlos syndromes have soft, velvety skin that is highly stretchy (elastic) and fragile. Affected individuals tend to bruise easily, and some types of the condition also cause abnormal scarring. People with the classical form of Ehlers-Danlos syndrome experience wounds that split open with little bleeding and leave scars that widen over time to create characteristic ""cigarette paper"" scars. The dermatosparaxis type of the disorder is characterized by loose skin that sags and wrinkles, and extra (redundant) folds of skin may be present.Some forms of Ehlers-Danlos syndrome, notably the vascular type and to a lesser extent the kyphoscoliotic, classical, and classical-like types, can cause unpredictable tearing (rupture) of blood vessels, leading to internal bleeding and other potentially life-threatening complications. The vascular type of Ehlers-Danlos syndrome is also associated with an increased risk of organ rupture, including tearing of the intestine and rupture of the uterus during pregnancy.Other types of Ehlers-Danlos syndrome have additional signs and symptoms. The cardiac-valvular type causes severe problems with the valves that control the movement of blood through the heart. People with the kyphoscoliotic type experience severe curvature of the spine that worsens over time and can interfere with breathing by restricting lung expansion. A type of Ehlers-Danlos syndrome called brittle cornea syndrome is characterized by thinness of the clear covering of the eye (the cornea) and other eye abnormalities. The spondylodysplastic type features short stature and skeletal abnormalities such as abnormally curved (bowed) limbs. Abnormalities of muscles, including hypotonia and permanently bent joints (contractures), are among the characteristic signs of the musculocontractural and myopathic forms of Ehlers-Danlos syndrome. The periodontal type causes abnormalities of the teeth and gums.
A condition associated with VENTRICULAR SEPTAL DEFECT and other congenital heart defects that allow the mixing of pulmonary and systemic circulation, increase blood flow into the lung, and subsequent responses to low oxygen in blood. This complex is characterized by progressive PULMONARY HYPERTENSION; HYPERTROPHY of the RIGHT VENTRICLE; CYANOSIS; and ERYTHROCYTOSIS.
Emotional, nutritional, financial, or physical maltreatment, exploitation, or abandonment of the older person generally by family members or by institutional personnel.
Substances that dissociate into two or more ions, to some extent, in water. Solutions of electrolytes thus conduct an electric current and can be decomposed by it (ELECTROLYSIS). (Grant & Hackh's Chemical Dictionary, 5th ed)
The process by which ELECTRONS are transported from a reduced substrate to molecular OXYGEN. (From Bennington, Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology, 1984, p270)
Enlargement of an area of the body due to obstruction within the lymphatic system and the resulting accumulation of lymph.
A clinical disorder that is caused by obstruction of the lymphatic system years after filarial infection. It is characterized by painful and profound lymphedema, resulting in significant swelling (elephantiasis) of extremities and genitals.
Excretory-related psychiatric disorders usually diagnosed in infancy or childhood.
A fused four ring compound occurring free or combined in galls. Isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye.
Pyrido-CARBAZOLES originally discovered in the bark of OCHROSIA ELLIPTICA. They inhibit DNA and RNA synthesis and have immunosuppressive properties.
An inherited blood disorder in which a large number of red blood cells have an elliptical morphology.
Ellis-van Creveld syndrome is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly, and dysplastic nails and teeth. Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals (summary by Ruiz-Perez et al., 2000). The clinical features of the Ellis-van Creveld syndrome appear to be identical regardless of whether the disorder is caused by mutation in the EVC gene (604831) or in the EVC2 gene (607261) (Ruiz-Perez et al., 2003, Galdzicka et al., 2002).
An extreme loss of muscle and subcutaneous fat that is caused by malnutrition, and which results in a severely thin (emaciated) appearance.
Blocking of a blood vessel by an embolus which can be a blood clot or other undissolved material in the blood stream.
Blocking of a blood vessel by air bubbles that enter the circulatory system, usually after TRAUMA; surgical procedures, or changes in atmospheric pressure.
Acute hypotension or cardiac arrest, acute hypoxia or coagulopathy in the absence of any other potential explanation related to the presence of amniotic fluid or the fetal debris within the maternal vascular system during the antepartum or intrapartum period.
Blocking of a blood vessel by fat deposits in the circulation. It is often seen after fractures of large bones or after administration of CORTICOSTEROIDS.
A tumor embolism involves sudden blockage of an artery by a clot or by other material from tumor fragments transported by the blood stream.
A muscarinic antagonist used mainly in the treatment of urinary syndromes. It is incompletely absorbed from the gastrointestinal tract and does not cross the blood-brain barrier.
Agents that cause vomiting. They may act directly on the gastrointestinal tract, bringing about emesis through local irritant effects, or indirectly, through their effects on the chemoreceptor trigger zone in the postremal area near the medulla.
The principal alkaloid of ipecac, from the ground roots of Uragoga (or Cephaelis) ipecacuanha or U. acuminata, of the Rubiaceae. It is used as an amebicide in many different preparations and may cause serious cardiac, hepatic, or renal damage and violent diarrhea and vomiting. Emetine inhibits protein synthesis in EUKARYOTIC CELLS but not PROKARYOTIC CELLS.
Purgative anthraquinone found in several plants, especially Rhamnus frangula. It was formerly used as a laxative, but is now used mainly as tool in toxicity studies.
A pathological accumulation of air in tissues or organs.
A condition when the SELLA TURCICA is not filled with pituitary tissue. The pituitary gland is either compressed, atrophied, or removed. There are two types: (1) primary empty sella is due a defect in the sella diaphragm leading to arachnoid herniation into the sellar space; (2) secondary empty sella is associated with the removal or treatment of PITUITARY NEOPLASMS.
An accumulation of pus in a body cavity, usually the pleural space.
Accumulation of pus in the pleural cavity.
An empyema resulting from infection by Mycobacterium tuberculosis.
A dicarbocyl-containing peptide and angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, enalapril is converted by de-esterification into its active form enalaprilat. Enalaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Enalapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
The active metabolite of ENALAPRIL and one of the potent, intravenously administered, ANGIOTENSIN-CONVERTING ENZYME INHIBITORS. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.
A sudden eruptiion (rash) of the surface of a mucous membrane of the mouth or pharynx.
An inflammatory process affecting the brain parenchyma. Causes include viral infections and less frequently bacterial infections, toxins, and immune-mediated processes.
A form of encephalitis, the etiology of which is uncertain, that is characterized by lethargy and headache.
A viral infection of the brain caused by serotypes of California encephalitis virus (ENCEPHALITIS VIRUS, CALIFORNIA) transmitted to humans by the mosquito AEDES triseriatus. The majority of cases are caused by the LA CROSSE VIRUS. This condition is endemic to the midwestern United States and primarily affects children between 5-10 years of age. Clinical manifestations include FEVER; VOMITING; HEADACHE; and abdominal pain followed by SEIZURES, altered mentation, and focal neurologic deficits. (From Joynt, Clinical Neurology, 1996, Ch26, p13)
A term that may be used to describe encephalitis characterized by sleepiness, which is likely due to a viral cause.
A mosquito-borne encephalitis caused by the Japanese B encephalitis virus (ENCEPHALITIS VIRUS, JAPANESE) occurring throughout Eastern Asia and Australia. The majority of infections occur in children and are subclinical or have features limited to transient fever and gastrointestinal symptoms. Inflammation of the brain, spinal cord, and meninges may occur and lead to transient or permanent neurologic deficits (including a POLIOMYELITIS-like presentation); SEIZURES; COMA; and death. (From Adams et al., Principles of Neurology, 6th ed, p751; Lancet 1998 Apr 11;351(9109):1094-7)
An acute or subacute inflammatory process of the CENTRAL NERVOUS SYSTEM characterized histologically by multiple foci of perivascular demyelination. Symptom onset usually occurs several days after an acute viral infection or immunization, but it may coincide with the onset of infection or rarely no antecedent event can be identified. Clinical manifestations include CONFUSION, somnolence, FEVER, nuchal rigidity, and involuntary movements. The illness may progress to COMA and eventually be fatal. (Adams et al., Principles of Neurology, 6th ed, p921)
A viral encephalitis caused by the St. Louis encephalitis virus (ENCEPHALITIS VIRUS, ST. LOUIS), a FLAVIVIRUS. It is transmitted to humans and other vertebrates primarily by mosquitoes of the genus CULEX. The primary animal vectors are wild birds and the disorder is endemic to the midwestern and southeastern United States. Infections may be limited to an influenza-like illness or present as an ASEPTIC MENINGITIS or ENCEPHALITIS. Clinical manifestations of the encephalitic presentation may include SEIZURES, lethargy, MYOCLONUS, focal neurologic signs, COMA, and DEATH. (From Adams et al., Principles of Neurology, 6th ed, p750)
Encephalitis caused by neurotropic viruses that are transmitted via the bite of TICKS. In Europe, the diseases are caused by ENCEPHALITIS VIRUSES, TICK-BORNE, which give rise to Russian spring-summer encephalitis, central European encephalitis, louping ill encephalitis, and related disorders. Powassan encephalitis occurs in North America and Russia and is caused by the Powassan virus. ASEPTIC MENINGITIS and rarely encephalitis may complicate COLORADO TICK FEVER which is endemic to mountainous regions of the western United States. (From Joynt, Clinical Neurology, 1996, Ch26, pp14-5)
A congenital defect in the skull, whereby there is a protrusion of part of the cranial contents through a congenital defect in the cranium, usually covered with skin or mucous membrane. The term encephalocele refers to a subclass of these lesions in which brain tissue protrudes through the defect.
A type of encephalocele (that is, a a protrusion of part of the cranial contents including brain tissue through a congenital opening in the cranium, typically covered with skin or mucous membrane) in the occipital region of the skull. Occipital encephalocele presents as a midline swelling over the occipital bone. It is usually covered with normal full-thickness scalp.
Encephalomalacia is the softening or loss of brain tissue after cerebral infarction, cerebral ischemia, infection, craniocerebral trauma, or other injury.
A disorder characterized by inflammation of both the brain and the spinal cord.
A picornavirus infection producing symptoms similar to poliomyelitis in pigs.
A group of ALPHAVIRUS INFECTIONS which affect horses and man, transmitted via the bites of mosquitoes. Disorders in this category are endemic to regions of South America and North America. In humans, clinical manifestations vary with the type of infection, and range from a mild influenza-like syndrome to a fulminant encephalitis. (From Joynt, Clinical Neurology, 1996, Ch26, pp8-10)
A degenerative brain disorder presenting with acute neurological manifestations. It usually associated with an acute infection or vaccination. It is characterized by brain hemorrhage, vascular necrosis and demyelination. Signs and symptoms include fever, headache, vomiting, convulsions and loss of consciousness.
A condition caused by infection by the Venezuelan equine encephalitis virus, which is characterized by headache, fever, myalgia, nausea, and vomiting.
Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis. When hemangiomata are associated, the condition is known as Maffucci syndrome (614569). Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to osteosarcoma (Schwartz et al., 1987). Classification of the Enchondromatoses In their classification of the enchondromatoses, Spranger et al. (1978) called Ollier disease and Maffucci syndrome types I and II enchondromatosis, respectively; metachondromatosis (156250), type III; spondyloenchondrodysplasia (607944), type IV; enchondromatosis with irregular vertebral lesions, type V; and generalized enchondromatosis, type VI. Halal and Azouz (1991) added 3 tentative categories to the 6 in the classification of Spranger et al. (1978). Pansuriya et al. (2010) suggested a new classification of enchondromatosis (multiple enchondromas).
An elimination disorder characterized by fecal incontinence, whether involuntary or intentional, which is not due to a medical condition and which occurs in someone who is toilet trained.
A spectrum of septal defects involving the ATRIAL SEPTUM; VENTRICULAR SEPTUM; and the atrioventricular valves (TRICUSPID VALVE; BICUSPID VALVE). These defects are due to incomplete growth and fusion of the ENDOCARDIAL CUSHIONS which are important in the formation of two atrioventricular canals, site of future atrioventricular valves.
A condition characterized by the thickening of ENDOCARDIUM due to proliferation of fibrous and elastic tissue, usually in the left ventricle leading to impaired cardiac function (CARDIOMYOPATHY, RESTRICTIVE). It is most commonly seen in young children and rarely in adults. It is often associated with congenital heart anomalies (HEART DEFECTS CONGENITAL;) INFECTION; or gene mutation. Defects in the tafazzin protein, encoded by TAZ gene, result in a form of autosomal dominant familial endocardial fibroelastosis.
An inflammation of the endocardium, the inner layer of the heart, which usually involves the heart valves.
A bacterial infection of the endocardium, the inner layer of the heart, which usually involves the heart valves.
ENDOCARDIUM infection that is usually caused by STREPTOCOCCUS. Subacute infective endocarditis evolves over weeks and months with modest toxicity and rare metastatic infection.
A polyp that arises from the endocervix. It is characterized by the presence of endocervical glands and a fibrovascular stroma.
A non-neoplastic or neoplastic disorder that affects the endocrine system. Representative examples of non-neoplastic disorders include diabetes mellitus, hyperthyroidism, and adrenal gland insufficiency. Representative examples of neoplastic disorders include carcinoid tumor, neuroendocrine carcinoma, and pheochromocytoma.
A benign or malignant neoplasm arising from the epithelial cells of an endocrine organ. Representative examples include pituitary gland adenoma, pituitary gland carcinoma, thyroid gland carcinoma, carcinoid tumor, and neuroendocrine carcinoma.
A non-seminomatous malignant germ cell tumor composed of primitive germ cells. It is the most common malignant germ cell tumor in the pediatric population. It occurs in the infant testis, ovary, sacrococcygeal region, vagina, uterus, prostate, abdomen, liver, retroperitoneum, thorax, and pineal/third ventricle. The tumor mimics the yolk sac of the embryo and produces alpha-fetoprotein (AFP). Treatment includes: surgical resection, radiation, and chemotherapy. This tumor is very responsive to chemotherapy regimens that include cisplatinum.
A benign, borderline, or malignant neoplasm that affects the endometrium.
A proliferation of the endometrial cells resulting in glandular enlargement and budding. The proliferation may or may not be associated with atypia of the endometrial cells. When the hyperplastic changes are excessive, there is formation of complex epithelial structures (complex endometrial hyperplasia).
A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum.
Endometriosis that affects the fallopian tube. Symptoms include infertility, pelvic pain, painful menstruation, and painful intercourse.
An acute or chronic, usually bacterial infectious process affecting the endometrium. It may extend to the myometrium and parametrial tissues. Symptoms include lower abdominal pain, vaginal discharge, and vaginal bleeding.
An infectious process affecting the internal structures of the eye.
Infection of the epicondyles by a parasite.
The transfer of energy of a given form among different scales of motion. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed). It includes the transfer of kinetic energy and the transfer of chemical energy. The transfer of chemical energy from one molecule to another depends on proximity of molecules so it is often used as in techniques to measure distance such as the use of FORSTER RESONANCE ENERGY TRANSFER.
A fluorinated ether and very potent and stable general anaesthetic agent. The mechanism through which enflurane exerts its effect is not clear, it probably acts on nerve cell membranes to disrupt neuronal transmission in the brain, probably via an action at the lipid matrix of the neuronal membrane. Enflurane may also enhance the activity of the inhibitory neurotransmitter gamma-aminobutyric acid on synaptic transmission. Enflurane may also inhibit glutamatergic excitatory transmission.
An eye that is more deeply recessed into the plane of the face than is typical.
A broad-spectrum 6-fluoronaphthyridinone antibacterial agent that is structurally related to NALIDIXIC ACID.
Infection with amoebae of the genus ENTAMOEBA. Infection with E. histolytica causes DYSENTERY, AMEBIC and LIVER ABSCESS, AMEBIC.
Inflammation of any segment of the SMALL INTESTINE.
An acute, highly contagious virus disease of turkeys characterized by chilling, anorexia, decreased water intake, diarrhea, dehydration and weight loss. The infectious agent is a CORONAVIRUS.
Infections with bacteria of the family ENTEROBACTERIACEAE.
An inflammation of the colon and small intestine. However, most conditions are either categorized as Enteritis (inflammation of the small intestine) or Colitis (inflammation of the large intestine).
An acute inflammation of the INTESTINAL MUCOSA that is characterized by the presence of pseudomembranes or plaques in the SMALL INTESTINE (pseudomembranous enteritis) and the LARGE INTESTINE (pseudomembranous colitis). It is commonly associated with antibiotic therapy and CLOSTRIDIUM DIFFICILE colonization.
Disease caused by the liberation of exotoxins of CLOSTRIDIUM PERFRINGENS in the intestines of sheep, goats, cattle, foals, and piglets. Type B enterotoxemia in lambs is lamb dysentery; type C enterotoxemia in mature sheep produces ""struck"", and in calves, lambs and piglets it produces hemorrhagic enterotoxemia; type D enterotoxemia in sheep and goats is pulpy-kidney disease or overeating disease.
An abnormal inversion (turning inward) of the eyelid (usually the lower) towards the globe. Entropion is usually acquired as a result of involutional or cicatricial processes but may occasionally be congenital.
An elimination disorder characterized by urinary incontinence, whether involuntary or intentional, which is not due to a medical condition and which occurs at or beyond an age at which continence is expected (usually 5 years).
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Compounds which restore enzymatic activity by removing an inhibitory group bound to the reactive site of the enzyme.
The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.
Abnormal increase of EOSINOPHILS in the blood, tissues or organs.
A clinical variant of Langerhans cell histiocytosis characterized by unifocal involvement of a bone (most often), skin, or lung. Patients are usually older children or adults usually presenting with a lytic bone lesion. The etiology is unknown. Morphologically, eosinophilic granuloma is characterized by the presence of Langerhans cells in a characteristic milieu which includes histiocytes, eosinophils, neutrophils, and small, mature lymphocytes.
Ependymomas are rare glial tumors of the brain and spinal cord (Yokota et al., 2003).
A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.
An Ephemerovirus infection of cattle caused by bovine ephemeral fever virus (EPHEMERAL FEVER VIRUS, BOVINE). It is characterized by respiratory symptoms, increased oropharyngeal secretions and lacrimation, joint pains, tremor, and stiffness.
A dehydroepiandrosterone metabolite and a precursor of testosterone and estradiol with hypolipidemic and anabolic property. Epiandrosterone, a potential neurosteroid, appears to bind to the gamma-aminobutyric acid (GABA)/benzodiazepine-receptor complex (GABA-RC), acting as a negative non-competitive modulator of GABA-RC as well as signal through the N-methyl-D-aspartate receptor. In addition this agent inhibits the pentose phosphate pathway (PPP) thereby dilating blood vessels pre-contracted by partial depolarization. Also, epiandrosterone inhibits the synthesis of thromboxane A2 in activated platelets, reduces plasma plasminogen activator inhibitor type 1 and tissue plasminogen activator antigen, increases serum levels of insulin-like growth factor 1 and increases cyclic guanosine monophosphate and nitric oxide synthesis. These effects may improve circulation in the microvasculature.
Keratoconjunctivitis resulting from infection by adenoviruses.
A benign cyst located in the dermis layer of skin that is lined by stratified squamous epithelium, and which contains laminated layers of keratin and keratin breakdown products.
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a severe skin reaction most often triggered by particular medications. Although Stevens-Johnson syndrome and toxic epidermal necrolysis were once thought to be separate conditions, they are now considered part of a continuum. Stevens-Johnson syndrome represents the less severe end of the disease spectrum, and toxic epidermal necrolysis represents the more severe end.SJS/TEN often begins with a fever and flu-like symptoms. Within a few days, the skin begins to blister and peel, forming very painful raw areas called erosions that resemble a severe hot-water burn. The skin erosions usually start on the face and chest before spreading to other parts of the body. In most affected individuals, the condition also damages the mucous membranes, including the lining of the mouth and the airways, which can cause trouble with swallowing and breathing. The painful blistering can also affect the urinary tract and genitals. SJS/TEN often affects the eyes as well, causing irritation and redness of the conjunctiva, which are the mucous membranes that protect the white part of the eye and line the eyelids, and damage to the clear front covering of the eye (the cornea).Severe damage to the skin and mucous membranes makes SJS/TEN a life-threatening disease. Because the skin normally acts as a protective barrier, extensive skin damage can lead to a dangerous loss of fluids and allow infections to develop. Serious complications can include pneumonia, overwhelming bacterial infections (sepsis), shock, multiple organ failure, and death. About 10 percent of people with Stevens-Johnson syndrome die from the disease, while the condition is fatal in up to 50 percent of those with toxic epidermal necrolysis.Among people who survive, long-term effects of SJS/TEN can include changes in skin coloring (pigmentation), dryness of the skin and mucous membranes (xerosis), excess sweating (hyperhidrosis), hair loss (alopecia), and abnormal growth or loss of the fingernails and toenails. Other long-term problems can include impaired taste, difficulty urinating, and genital abnormalities. A small percentage of affected individuals develop chronic dryness or inflammation of the eyes, which can lead to increased sensitivity to light (photophobia) and vision impairment.
An acute generalized dermatitis of pigs which occurs from 5 to 35 days of age, characterized by sudden onset, with morbidity of 10 to 90% and mortality of 5 to 90%. The lesions are caused by Staphylococcus hyos but the bacterial agent is unable to penetrate the intact skin. Abrasions on the feet and legs or lacerations on the body frequently precede infection. In acute cases, a vesicular-type virus may be the predisposing factor. The causative organism is inhibited by most antibiotics. (Merck Veterinary Manual, 5th ed)
Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000). Genetic Heterogeneity of Susceptibility to Epidermodysplasia Verruciformis Susceptibility to EV2 (618231) is conferred by mutation in the TMC8 gene (605829) on chromosome 17q25; EV3 (618267) by mutation in the CIB1 gene (602293) on chromosome 15q26; EV4 (618307) by mutation in the RHOH gene (602037) on chromosome 4p13; and EV5 (618309) by mutation in the IL7 gene (146660) on chromosome 8q12.
An autosomal recessive inherited skin disorder caused by mutations in the genes encoding keratins 5 and 14, collagen VII or laminin 5. It is characterized by skin fragility and the formation of blisters. The blisters may become large and ulcerated, resulting in skin infections and loss of body fluids.
Inflammation of the EPIDIDYMIS. Its clinical features include enlarged epididymis, a swollen SCROTUM; PAIN; PYURIA; and FEVER. It is usually related to infections in the URINARY TRACT, which likely spread to the EPIDIDYMIS through either the VAS DEFERENS or the lymphatics of the SPERMATIC CORD.
A primary or metastatic neoplasm that involves the space between the vertebral periosteum and dura mater that surrounds the spinal cord.
A brain disorder characterized by episodes of abnormally increased neuronal discharge resulting in transient episodes of sensory or motor neurological dysfunction, or psychic dysfunction. These episodes may or may not be associated with loss of consciousness or convulsions.
A seizure caused by a localized disorder.
A chronic condition characterised by recurrent generalised seizures.
A generalized seizure disorder characterized by recurrent major motor seizures. The initial brief tonic phase is marked by trunk flexion followed by diffuse extension of the trunk and extremities. The clonic phase features rhythmic flexor contractions of the trunk and limbs, pupillary dilation, elevations of blood pressure and pulse, urinary incontinence, and tongue biting. This is followed by a profound state of depressed consciousness (post-ictal state) which gradually improves over minutes to hours. The disorder may be cryptogenic, familial, or symptomatic (caused by an identified disease process). (From Adams et al., Principles of Neurology, 6th ed, p329)
A clinically diverse group of epilepsy syndromes characterized either by myoclonic seizures or by myoclonus in association with other seizure types. Myoclonic epilepsy syndromes are divided into three subtypes based on etiology: familial, cryptogenic, and symptomatic.
Recurrent absence seizures are generalized seizures and are characterized by a loss of consciousness, thus, are a form of dialeptic seizures.
A localization-related (focal) form of epilepsy characterized by recurrent seizures that arise from foci within the TEMPORAL LOBE, most commonly from its mesial aspect. A wide variety of psychic phenomena may be associated, including illusions, hallucinations, dyscognitive states, and affective experiences. The majority of complex partial seizures (see EPILEPSY, COMPLEX PARTIAL) originate from the temporal lobes. Temporal lobe seizures may be classified by etiology as cryptogenic, familial, or symptomatic. (From Adams et al., Principles of Neurology, 6th ed, p321).
A synthetic steroid with estrogenic activity.
The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
Abnormal separation of an epiphysis from the shaft of a bone.
4-Methoxy-2-(5-methoxy-3-methylpyrazol-1-yl)-6-methylpyrimidine. A pyrimidinyl pyrazole with antipyretic, analgesic, and anti-inflammatory activity.
A 4'-epi-isomer of the anthracycline antineoplastic antibiotic doxorubicin. Epirubicin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis. This agent also produces toxic free-radical intermediates and interacts with cell membrane lipids causing lipid peroxidation.
Inflammation of the episclera, a thin layer of tissue covering the white part (sclera) of the eye.
A birth defect due to malformation of the URETHRA in which the urethral opening is above its normal location. In the male, the malformed urethra generally opens on the top or the side of the PENIS, but the urethra can also be open the entire length of the penis. In the female, the malformed urethral opening is often between the CLITORIS and the labia, or in the ABDOMEN.
An estrogenic steroid produced by HORSES. It has a total of five double bonds in the A- and B-ring. High concentration of equilenin is found in the URINE of pregnant mares.
A naturally occurring steroid with estrogenic activity obtained from the urine of pregnant mares.
A horse disease caused by a retrovirus which is transmitted by biting flies. The acute phase symptoms include high fever, anemia, weakness, and swelling of the legs. The subacute phase symptoms include splenomegaly, anemia, and weight loss. The chronic phase symptoms include recurrent fevers and anemia.
Vitamin D2, a fat-soluble vitamin important for many biochemical processes including the absorption and metabolism of calcium and phosphorus. In vivo, ergocalciferol is formed after sun (ultraviolet) irradiation of plant-derived ergosterol, another form of vitamin D. Ergocalciferol is the form of vitamin D usually found in vitamin supplements. (NCI04)
An ergot alkaloid (ERGOT ALKALOIDS) with uterine and VASCULAR SMOOTH MUSCLE contractile properties.
A steroid occurring in FUNGI. Irradiation with ULTRAVIOLET RAYS results in formation of ERGOCALCIFEROL (vitamin D2).
Alkaloids originally isolated from the ergot fungus Claviceps purpurea (Hypocreaceae). They include compounds that are structurally related to ergoline (ERGOLINES) and ergotamine (ERGOTAMINES). Many of the ergot alkaloids act as alpha-adrenergic antagonists.
A mixture of the mesylates (methane sulfonates) of DIHYDROERGOCORNINE; DIHYDROERGOCRISTINE; and the alpha- and beta-isomers of DIHYDROERGOCRYPTINE. The substance produces a generalized peripheral vasodilation and a fall in arterial pressure and has been used to treat symptoms of mild to moderate impairment of mental function in the elderly.
A naturally occurring ergot alkaloid with vasoconstrictor and analgesic property. Ergotamine selectively binds and activates serotonin (5-HT) 1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, thereby resulting in vasoconstriction and reducing the blood flow in cerebral arteries that may lead to relieve of vascular headaches. This agent also selectively binds to alpha-adrenergic receptors, thereby stimulating vascular smooth muscle and causing vasoconstriction in both arteries and veins, which also contributes to the relief of headaches. Furthermore, the activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
A monounsaturated very long-chain fatty acid with a 22-carbon backbone and a single double bond originating from either the 3rd, 7th, 9th, 11th or 17th positions from the methyl end.
The ejection of gas or air through the mouth from the stomach.
Increased susceptibility to erysipelas, as manifested by a medical history of repeated episodes of erysipelas, which is a superficial infection of the skin, typically involving the lymphatic system. [HPO:probinson]
Infections with bacteria of the genus ERYSIPELOTHRIX.
A cutaneous eruption that consists of multiple (at least two) concentric erythematous rings.
A type of panniculitis characterized histologically by the presence of granulomas, vasculitis, and necrosis. It is traditionally considered to be the tuberculous counterpart of nodular vasculitis, but is now known to occur without tuberculous precedent. It is seen most commonly in adolescent and menopausal women, is initiated or exacerbated by cold weather, and typically presents as one or more recurrent erythrocyanotic nodules or plaques on the calves. The nodules may progress to form indurations, ulcerations, and scars.
A hypersensitivity reaction characterized by the sudden appearance of symmetrical cutaneous and mucocutaneous macular or papular lesions which evolve into lesions with bright red borders (target lesions). The lesions usually appear in the hands, feet, extremities, and face. Symptoms include fever, malaise, sore throat, cough, vomiting, diarrhea, arthralgia, and myalgia. Causes include infections (most commonly herpes simplex virus), drugs (e.g., sulfonamides, anticonvulsants, and antibiotics), malignancies, and collagen vascular disorders.
An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral.
A skin condition that primarily affects the scalp and face and presents as scaly inflammation. Examples include itchy, dry skin and dandruff.
A chronic bacterial infection of major folds of the skin, caused by Corynebacterium minutissimum.
A four-carbon sugar that is found in algae, fungi, and lichens. It is twice as sweet as sucrose and can be used as a coronary vasodilator.
A vasodilator with general properties similar to NITROGLYCERIN. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1020)
A condition characterized by the abnormal presence of ERYTHROBLASTS in the circulation of the FETUS or NEWBORNS. It is a disorder due to BLOOD GROUP INCOMPATIBILITY, such as the maternal alloimmunization by fetal antigen RH FACTORS leading to HEMOLYSIS of ERYTHROCYTES, hemolytic anemia (ANEMIA, HEMOLYTIC), general edema (HYDROPS FETALIS), and SEVERE JAUNDICE IN NEWBORN.
A laboratory test result indicating an abnormally high quantity of immature red blood cells.
A peripheral arterial disease that is characterized by the triad of ERYTHEMA, burning PAIN, and increased SKIN TEMPERATURE of the extremities (or red, painful extremities). Erythromelalgia may be classified as primary or idiopathic, familial or non-familial. Secondary erythromelalgia is associated with other diseases, the most common being MYELOPROLIFERATIVE DISORDERS.
SCN9A-related inherited erythromelalgia (SCN9A-related IEM) is characterized by recurrent attacks of bilateral and symmetric intense pain, redness, warmth, and swelling involving the feet and, less frequently, the hands. SCN9A-related IEM is not associated with an organic disease. Manifestations may vary within a family. Onset is usually in childhood or adolescence but has been recognized in infants and adults. At onset, episodes are triggered by warmth; other precipitating factors include: exercise, tight shoes, wearing socks, alcohol, spicy foods, and other vasodilating agents. In advanced disease, symptoms may occur many times a day or become constant. Some individuals have allodynia (pain evoked by a normally innocuous stimulus) and hyperalgesia (increased sensitivity to a painful stimulus). Episodes may be disabling, interfere with sleep, and severely limit normal activities such as walking, participation in sports, wearing socks and shoes, and attending school or going to work.
A clinical term that refers to the presence of a red flat and well defined lesion on the oral mucosa that is not caused by trauma, vascular, or inflammatory processes. It is a precancerous condition and is seen more commonly in middle aged or older males. It is associated with tobacco and alcohol consumption. Microscopic examination reveals severe epithelial dysplasia, carcinoma in situ, or invasive squamous cell carcinoma.
Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.
Increased susceptibility to infections with Escherichia coli, as manifested by recurrent episodes of infection with this agent.
Pentacyclic triterpene saponins, biosynthesized from protoaescigenin and barringtogenol, occurring in the seeds of AESCULUS. It inhibits edema formation and decreases vascular fragility.
A derivative of COUMARIN with molecular formula C15H16O9.
A disorder of esophageal motility characterized by the inability of the lower esophageal sphincter to relax during swallowing and by inadequate or lacking peristalsis in the lower half of the body of the esophagus.
A congenital abnormality of the esophagus in which the upper esophagus ends as a blind pouch and does not connect with the lower esophagus; it is often accompanied by a tracheoesophageal fistula. Signs and symptoms in a newborn with this abnormality include excessive salivation, choking, coughing, and the development of cyanosis and respiratory distress when fed.
Any fluid-filled closed cavity or sac (CYSTS) that is lined by an EPITHELIUM and found in the ESOPHAGUS region.
A non-neoplastic or neoplastic disorder that affects the esophagus. Representative examples of non-neoplastic disorders include esophagitis and esophageal ulcer. Representative examples of neoplastic disorders include carcinomas, lymphomas, and melanomas.
Saccular protrusion beyond the wall of the ESOPHAGUS.
Abnormal passage communicating with the ESOPHAGUS. The most common type is TRACHEOESOPHAGEAL FISTULA between the esophagus and the TRACHEA.
Disorders affecting the motor function of the UPPER ESOPHAGEAL SPHINCTER; LOWER ESOPHAGEAL SPHINCTER; the ESOPHAGUS body, or a combination of these parts. The failure of the sphincters to maintain a tonic pressure may result in gastric reflux of food and acid into the esophagus (GASTROESOPHAGEAL REFLUX). Other disorders include hypermotility (spastic disorders) and markedly increased amplitude in contraction (nutcracker esophagus).
A benign or malignant neoplasm involving the esophagus.
An opening or hole in the ESOPHAGUS that is caused by TRAUMA, injury, or pathological process.
A hypermotility disorder of the ESOPHAGUS that is characterized by spastic non-peristaltic responses to SWALLOWING; CHEST PAIN; and DYSPHAGIA.
A pathological narrowing of the esophagus that is caused by the development of a ring of scar tissue that constricts the esophageal lumen.
Abnormally dilated veins of the esophagus.
An acute or chronic inflammatory process affecting the esophageal wall.
INFLAMMATION of the ESOPHAGUS that is caused by the reflux of GASTRIC JUICE with contents of the STOMACH and DUODENUM.
A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a ""cross-eye"" appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze.
A benzodiazepine with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than DIAZEPAM or NITRAZEPAM.
A steroid sex hormone vital to the maintenance of fertility and secondary sexual characteristics in females. Typically esterified, estradiol derivatives are formulated for oral or parenteral administration. As the primary, most potent estrogen hormone produced by the ovaries, estradiol binds to and activates specific nuclear receptors. Estradiol exhibits mild anabolic and metabolic properties, and increases blood coagulability.
Compounds which inhibit or antagonize the biosynthesis or action of estradiol.
A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties.
The orally available disodium salt, monohydrate, of estramustine phosphate, a synthetic molecule that combines estradiol and nornitrogen mustard through a carbamate link. Estramustine and its major metabolite estramustine bind to microtubule-associated proteins (MAPs) and tubulin, thereby inhibiting microtubule dynamics and leading to anaphase arrest in a dose-dependent fashion. This agent also exhibits anti-androgenic effects.
A hydroxylated metabolite of ESTRADIOL or ESTRONE that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During PREGNANCY, a large amount of estriol is produced by the PLACENTA. Isomers with inversion of the hydroxyl group or groups are called epiestriol.
Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.
A pharmaceutical preparation containing a mixture of water-soluble, conjugated estrogens derived wholly or in part from URINE of pregnant mares or synthetically from ESTRONE and EQUILIN. It contains a sodium-salt mixture of estrone sulfate (52-62%) and equilin sulfate (22-30%) with a total of the two between 80-88%. Other concomitant conjugates include 17-alpha-dihydroequilin, 17-alpha-estradiol, and 17-beta-dihydroequilin. The potency of the preparation is expressed in terms of an equivalent quantity of sodium estrone sulfate.
A class of natural or synthetic hormones that binds to a cytoplasmic receptor and initiates translocation of the hormone-receptor complex to the nucleus of target cells of tissues rich in estrogen receptors, including the endometrium, myometrium, oviduct, vagina, fallopian tube, cervix, brain, liver, placenta, ovarian cells, Leydigs cells, kidney, prostate, pancreas, heart, and skin. (NCI)
Estrogens that are not steroids, but have a structural configuration resembling steroids and may mimic steroidal estrogen effect or bind to estrogen receptors.
Compounds obtained by chemical synthesis which possess estrogenic activity, but differ in structure from naturally occurring estrogens.
An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from ANDROSTENEDIONE directly, or from TESTOSTERONE via ESTRADIOL. In humans, it is produced primarily by the cyclic ovaries, PLACENTA, and the ADIPOSE TISSUE of men and postmenopausal women.
A potent phosphodiesterase inhibitor proposed as an antipsychotic agent.
A topically applied anti-infective agent.
The sodium salt form of ethacrynic acid, an unsaturated ketone derivative of aryloxyacetic acid without a sulfonamide substituent belonging to the class of loop diuretics. Ethacrynic acid is extensively bound to plasma proteins; both ethacrynic acid in its unchanged form as well as its metabolites are excreted in bile and urine.
A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.
An antibiotic with bacteriostatic, antimicrobial and antitubercular properties. Ethambutol interferes with the biosynthesis of arabinogalactan, a major polysaccharide of the mycobacterial cell wall. It inhibits the polymerization of cell wall arabinan of arabinogalactan and lipoarabinomannan by blocking arabinosyl transferases and induces the accumulation of D-arabinofuranosyl-P-decaprenol, an intermediate in arabinan biosynthesis. This results in halting bacterial growth.
Benzenesulfonate derivative used as a systemic hemostatic.
A member of the class of tertiary carbinols with sedative and hypnotic properties. Ethchlorvynol appears to depress the central nervous system by binding at a benzodiazepine-GABA-A-chloride ionophore receptor complex, located in the limbic, thalamic and hypothalamic regions of the central nervous system (CNS). This increases the frequency of chloride channel opening, allowing the flow of chloride ions into the neuron and ultimately leading to membrane hyperpolarization and a decrease in neuronal excitability.
A mobile, very volatile, highly flammable liquid used as an inhalation anesthetic and as a solvent for waxes, fats, oils, perfumes, alkaloids, and gums. It is mildly irritating to skin and mucous membranes.
An organic compound in which two carbon atoms are linked through an oxygen atom (C-O-C). An ether may be a product of the condensation of alcohols. Ether also refers loosely to diethyl-ether, a colorless, volatile, highly inflammable liquid used in industry and biomedical research, and historically important as an anesthetic agent. In vivo, ether acts similarly to alcohol and chloroform, but its stimulant action on the heart is much more marked. Ether is a rapidly diffusible stimulant. (NCI04)
A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide.
A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.
A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.
A nicotinamide derivative, with antibacterial activity, used to treat tuberculosis. Although the exact mechanism of action of ethionamide is unknown, it may inhibit the synthesis of mycolic acid, a saturated fatty acid found in the bacterial cell wall, thereby inhibiting bacterial cell wall synthesis. This eventually leads to bacterial cell wall disruption and cell lysis. Ethionamide may be bacteriostatic or bactericidal in action, depending on the concentration of the drug at the site of infection and the susceptibility of the organism involved.
17 alpha-Hydroxypregn-4-en-20-yn-3-one. A synthetic steroid hormone with progestational effects.
An acute or chronic inflammatory process affecting the mucous membrane of the ethmoid sinus.
Alkylating antineoplastic agent used especially in bladder neoplasms. It is toxic to hair follicles, gastro-intestinal tract, and vasculature.
An inhibitor of folate metabolism. It is used as a coccidiostat in poultry.
A succinimide with anticonvulsant activity. The exact mechanism of action is not entirely understood, but most likely ethosuximide exerts its effects by partial antagonism of T-type calcium channels of the thalamic neurons. This leads to a decrease in burst firing of thalamocortical neurons, which stabilizes the nerve activity in the brain and prevents seizures.
A hydantoin anticonvulsant with anti-epileptic activity. The mechanism of action is not completely known, but is thought to be fairly similar to phenytoin. Ethotoin influences synaptic transmission by altering sodium and calcium ion influx across neuronal membranes in the repolarization, depolarization, and membrane stability phase and interferes with the calcium uptake in presynaptic terminals. This inhibits neuronal firing and results in the stabilization of neuronal membranes, thereby preventing the spread of seizure activity at the motor cortex.
Antioxidant; also a post-harvest dip to prevent scald on apples and pears.
A carbonic anhydrase inhibitor used as diuretic and in glaucoma. It may cause hypokalemia.
A coumarin that is used as an anticoagulant. It has actions similar to those of WARFARIN. (From Martindale, The Extra Pharmacopoeia, 30th ed, p226)
A gas that condenses under slight pressure. Because of its low boiling point ethyl chloride sprayed on skin produces an intense cold by evaporation. Cold blocks nerve conduction. Ethyl chloride has been used in surgery but is primarily used to relieve local pain in sports medicine.
A sulfonoxyalkane with carcinogenic and teratogenic properties. Ethyl methanesulfonate ethylates DNA, thereby damaging DNA and leading to genetic mutations, single-stranded breaks in DNA, and chromosomal aberrations. Ethyl methanesulfonate may be used experimentally in biomedical research. (NCI04)
An anabolic steroid with some progestational activity and little androgenic effect.
A narcotic analgesic and antitussive. It is metabolized in the liver by ETHYLMORPHINE-N-DEMETHYLASE and used as an indicator of liver function.
A phenylephrine-related beta-1 adrenergic and alpha adrenergic agonist used as a cardiotonic and antihypotensive agent.
A synthetic progestational hormone used alone or in combination with estrogens as an oral contraceptive.
A local anesthetic with rapid onset and long action, similar to BUPIVACAINE.
A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.
A xanthine-related, putative nootropic drug.
An imidazole derivative with short-acting sedative, hypnotic, and general anesthetic properties. Etomidate appears to have gamma-aminobutyric acid (GABA) like effects, mediated through GABA-A receptor. The action enhances the inhibitory effect of GABA on the central nervous system by causing chloride channel opening events which leads to membrane hyperpolarization.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
A narcotic analgesic morphinan used as a sedative in veterinary practice.
A synthetic oral retinoid that is a prodrug of acitretin. Etretinate activates retinoid receptors, causing an induction of cell differentiation, inhibition of cell proliferation, and inhibition of tissue infiltration by inflammatory cells. Etretinate is no longer commercially available in the U.S. due to the extended potential for teratogenic effects related to its long half-life. (NCI04)
A cinnamate derivative of the shikamate pathway found in CLOVE OIL and other PLANTS.
Abnormal thyroid function tests, low triiodothyronine with elevated reverse triiodothyronine, in the setting of non-thyroidal illness.
An acute, short-lived, viral disease of infants and young children characterized by a high fever at onset that drops to normal after 3-4 days and the concomitant appearance of a macular or maculopapular rash that appears first on the trunk and then spreads to other areas. It is the sixth of the classical exanthematous diseases and is caused by HHV-6; (HERPESVIRUS 6, HUMAN). (From Dorland, 27th ed)
Sudden contraction of the smooth muscles of the bronchial wall that occurs during or following exercise.
A disorder characterized by recurrent sexual urges, fantasies, or behaviors involving the exposure of one's genitals to an unsuspecting stranger.
Abnormal protrusion of both eyes; may be caused by endocrine gland malfunction, malignancy, injury, or paralysis of the extrinsic muscles of the eye.
The disorder hereditary multiple osteochondromas (HMO), previously called hereditary multiple exostoses (HME), is characterized by growths of multiple osteochondromas (benign cartilage-capped bone tumors that grow outward from the metaphyses of long bones). Osteochondromas can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature, premature osteoarthrosis, and compression of peripheral nerves. The median age of diagnosis is three years; nearly all affected individuals are diagnosed by age 12 years. The risk for malignant degeneration to osteochondrosarcoma increases with age, although the lifetime risk of malignant degeneration is low (~1%).
A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction.
Agents that increase mucous excretion. Mucolytic agents, that is drugs that liquefy mucous secretions, are also included here.
The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV.
Eversion of a hollow organ and exposure, inside out, and protruded through the abdominal wall.
A movement disorder caused by defects in the basal ganglia. The clinical manifestations include changes in the muscle tone, dyskinesia, and akinesia. Causes include vascular disorders, degenerative disorders, and antipsychotic drugs.
The leakage of body fluid or cells from the vascular system to the surrounding tissues. This process occurs either by force or as a result of a pathologic reaction (e.g., inflammation). This process may sometimes allow cancer cells to migrate from capillaries to adjacent tissues, initiating micro-metastases.
A disorder of the eye that is present at birth. Representative examples include congenital cataract, congenital glaucoma, and astigmatism.
A non-neoplastic or neoplastic disorder that affects the eye. Representative examples include conjunctivitis, glaucoma, cataract, conjunctival squamous cell carcinoma, uveal melanoma, and retinoblastoma.
Transmission of gene defects or chromosomal aberrations/abnormalities which are expressed in extreme variation in the structure or function of the eye. These may be evident at birth, but may be manifested later with progression of the disorder.
Bleeding from vessels of the various tissues of the eye.
An infectious process affecting any part of the eye. Causes include viruses and bacteria. Symptoms include itching and discomfort in the eye, watery eyes, eye pain and discharge, and blurring vision. Representative examples include pink eye, blepharitis, and trachoma.
Infections in the inner or external eye caused by microorganisms belonging to several families of bacteria. Some of the more common genera found are Haemophilus, Neisseria, Staphylococcus, Streptococcus, and Chlamydia.
Infection by a variety of fungi, usually through four possible mechanisms: superficial infection producing conjunctivitis, keratitis, or lacrimal obstruction; extension of infection from neighboring structures - skin, paranasal sinuses, nasopharynx; direct introduction during surgery or accidental penetrating trauma; or via the blood or lymphatic routes in patients with underlying mycoses.
Mild to severe infections of the eye and its adjacent structures (adnexa) by adult or larval protozoan or metazoan parasites.
Infections of the eye caused by minute intracellular agents. These infections may lead to severe inflammation in various parts of the eye - conjunctiva, iris, eyelids, etc. Several viruses have been identified as the causative agents. Among these are Herpesvirus, Adenovirus, Poxvirus, and Myxovirus.
Ocular disorders attendant upon non-ocular disease or injury.
A benign or malignant neoplasm affecting the structures of the eye.
A benign or malignant neoplasm that affects the eyelid. Representative examples include hemangioma, nevus, and carcinoma.
Observable changes of expression in the face in response to emotional stimuli.
A rare acquired disorder with characteristics of unilateral slowly progressive atrophy of the skin and soft tissues of half of the face leading to a sunken appearance. Muscles, cartilage and the underlying bony structures may also be involved. Usually presents during the first 20 years of life and may start with alopecia, hair hypopigmentation, and atrophy. May extend to the upper lip and or one side of the tongue and the masticatory muscles, resulting in deviation of the nose and or mouth toward the affected side. Rarely both sides of the face and the skin on the arms/trunk/leg or the entire body may be involved. Autoimmunity may be a cause along with facial or head trauma, meningoencephalitis, abnormal development or hyperactivity of the sympathetic nervous system, neuro-vasculitis, angiogenesis anomalies, and slow viral infections. Sporadic but rare familial cases have been reported.
A tumor (abnormal growth of tissue) of the face.
A non-neoplastic or neoplastic disorder affecting the facial nerve (seventh cranial nerve).
Neuralgic syndromes which feature chronic or recurrent FACIAL PAIN as the primary manifestation of disease. Disorders of the trigeminal and facial nerves are frequently associated with these conditions.
Pain in the facial region including orofacial pain and craniofacial pain. Associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves. Conditions which feature recurrent or persistent facial pain as the primary manifestation of disease are referred to as FACIAL PAIN SYNDROMES.
Complete loss of ability to move facial muscles innervated by the facial nerve (i.e., the seventh cranial nerve).
A category of psychiatric disorders which are characterized by physical or psychological symptoms that are intentionally produced in order to assume the sick role; there is no external incentive for the behavior, such as economic gain or avoiding legal responsibility, and the person is unaware of any self-motivating factors.
Storage-stable blood coagulation factor acting in the intrinsic pathway of blood coagulation. Its activated form, IXa, forms a complex with factor VIII and calcium on platelet factor 3 to activate factor X to Xa. Deficiency of factor IX results in HEMOPHILIA B (Christmas Disease).
Factor V Leiden thrombophilia is characterized by a poor anticoagulant response to activated protein C (APC) and an increased risk for venous thromboembolism (VTE). Deep vein thrombosis (DVT) is the most common VTE, with the legs being the most common site. Thrombosis in unusual locations is less common. Evidence suggests that heterozygosity for the Leiden variant has at most a modest effect on risk for recurrent thrombosis after initial treatment of a first VTE. It is unlikely that factor V Leiden thrombophilia (i.e., heterozygosity or homozygosity for the Leiden variant) is a major factor contributing to pregnancy loss and other adverse pregnancy outcomes (preeclampsia, fetal growth restriction, and placental abruption). The clinical expression of factor V Leiden thrombophilia is influenced by the following: The number of Leiden variants (heterozygotes have a slightly increased risk for venous thrombosis; homozygotes have a much greater thrombotic risk). Coexisting genetic thrombophilic disorders, which have a supra-additive effect on overall thrombotic risk. Acquired thrombophilic disorders: antiphospholipid antibody (APLA) syndrome, paroxysmal nocturnal hemoglobinuria, myeloproliferative disorders, and increased levels of clotting factors. Circumstantial risk factors including but not limited to pregnancy, central venous catheters, travel, combined oral contraceptive (COC) use and other combined contraceptives, oral hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), obesity, leg injury, and advancing age.
Coagulation factor VII (466 aa, ~52 kDa) is encoded by the human F7 gene. This protein is involved in both binding to tissue factor and the initiation of blood coagulation.
Factor VII deficiency is an autosomal recessive bleeding disorder showing variable severity (summary by Millar et al., 2000). Perry (2002) provided a comprehensive review of factor VII deficiency with a description of F7 polymorphisms, gene structure, and a summary of 120 mutations.
Activated form of factor VII. Factor VIIa activates factor X in the extrinsic pathway of blood coagulation.
Factor VIII of blood coagulation. Antihemophilic factor that is part of the factor VIII/von Willebrand factor complex. Factor VIII is produced in the liver and acts in the intrinsic pathway of blood coagulation. It serves as a cofactor in factor X activation and this action is markedly enhanced by small amounts of thrombin.
Factor X deficiency is a rare autosomal recessive bleeding disorder showing variable phenotypic severity. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. The disorder can be caused either by reduced levels of the factor X protein or by synthesis of a dysfunctional factor X protein (summary by Millar et al., 2000).
Factor XI deficiency is an autosomal bleeding disorder characterized by reduced levels of factor XI in plasma (less than 15 IU/dL). Bleeding occurs mainly after trauma or surgery. On the basis of the concordance or discordance of F11 antigen and activity, the disorder is classified into the more frequent cross-reactive negative (CRM-) and the rarer CRM positive (CRM+) (summary by Duga and Salomon, 2009).
A coagulation disorder characterized by the partial or complete absence of factor XII activity in the blood. It is not associated with increased bleeding risk.
A fibrin-stabilizing plasma enzyme (TRANSGLUTAMINASES) that is activated by THROMBIN and CALCIUM to form FACTOR XIIIA. It is important for stabilizing the formation of the fibrin polymer (clot) which culminates the coagulation cascade.
A deficiency of blood coagulation FACTOR XIII or fibrin stabilizing factor (FSF) that prevents blood clot formation and results in a clinical hemorrhagic diathesis.
A clinical finding indicating less than normal growth in an infant or child, or a state of global decline in an adult.
A non-neoplastic or neoplastic disorder that affects the fallopian tube. Representative examples of non-neoplastic disorders include salpingitis and endometriosis. Representative examples of neoplastic disorders include papilloma, adenofibroma, carcinoma, leiomyosarcoma, and carcinosarcoma.
A benign or malignant neoplasm affecting the fallopian tube. Representative examples of benign neoplasms include papilloma, adenofibroma, and leiomyoma. Representative examples of malignant neoplasms include carcinoma, carcinosarcoma, and adenosarcoma.
A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion.
A genetic or acquired disorder characterized by impairment of the function of the proximal tubules of the kidney. It results in decreased reabsorption of electrolytes, glucose, amino acids, and other nutrients.
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, gastrointestinal tract, and genitourinary tract – are more common in individuals with FA.
A form of alveolitis or pneumonitis due to an acquired hypersensitivity to inhaled antigens associated with farm environment. Antigens in the farm dust are commonly from bacteria actinomycetes (SACCHAROPOLYSPORA and THERMOACTINOMYCES), fungi, and animal proteins in the soil, straw, crops, pelts, serum, and excreta.
A colorless liquid extracted from oils of plants such as citronella, neroli, cyclamen, and tuberose. It is an intermediate step in the biological synthesis of cholesterol from mevalonic acid in vertebrates. It has a delicate odor and is used in perfumery. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.
Inflammation of fascia, the tissue under the skin and over the muscle.
A parasitic infection that is caused by liver flukes, usually Fasciola hepatica, of sheep, goats, and cattle. Humans become infected by eating uncooked, infested aquatic vegetation (classically watercress). Adult flukes inhabit the bile ducts, gallbladder, and occasionally ectopic sites. Symptoms arise secondary to inflammatory response or obstruction.
Infection of cattle and other herbivores with the giant liver fluke Fascioloides magna. It is characterized by extensive destruction of the liver parenchyma.
A small bowel infection that is caused by Fasciolopsis buski, which is endemic in the Far East and Southeast Asia, and which is transmitted via the consumption of raw or undercooked aquatic plants. The spectrum of manifestations range from asymptomatic to intestinal symptoms from local invasion or allergic response.
Emulsions of fats or lipids used primarily in parenteral feeding.
A condition in which the death of adipose tissue results in neutral fats being split into fatty acids and glycerol.
A subjective feeling of tiredness characterized by a lack of energy and motivation.
A syndrome characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration or longer. Symptoms are not caused by ongoing exertion; are not relieved by rest; and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Minor alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome. There is also considerable overlap between this condition and FIBROMYALGIA. (From Semin Neurol 1998;18(2):237-42; Ann Intern Med 1994 Dec 15;121(12): 953-9)
The glyceryl esters of a fatty acid, or of a mixture of fatty acids. They are generally odorless, colorless, and tasteless if pure, but they may be flavored according to origin. Fats are insoluble in water, soluble in most organic solvents. They occur in animal and vegetable tissue and are generally obtained by boiling or by extraction under pressure. They are important in the diet (DIETARY FATS) as a source of energy. (Grant & Hackh's Chemical Dictionary, 5th ed)
A group of unsaturated fatty acids occurring mainly in fish oils, with three double bonds at particular positions in the hydrocarbon chain.
Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.
Lipid infiltration of the hepatic parenchymal cells that is due to ALCOHOL ABUSE. The fatty changes in the alcoholic fatty liver may be reversible, depending on the amounts of TRIGLYCERIDES accumulated.
A condition associated with glucose-6-phosphate dehydrogenase deficiency, which is characterized by hemolysis.
Fazio-Londe disease is a progressive bulbar palsy with onset in childhood that presents with hypotonia and respiratory insufficiency (summary by Bosch et al., 2011).
Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus.
Formation of a firm impassable mass of stool in the RECTUM or distal COLON.
A highly contagious DNA virus infection of the cat family, characterized by fever, enteritis and bone marrow changes. It is also called feline ataxia, feline agranulocytosis, feline infectious enteritis, cat fever, cat plague, and show fever. It is caused by FELINE PANLEUKOPENIA VIRUS or the closely related MINK ENTERITIS VIRUS or CANINE PARVOVIRUS.
A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels.
A rare complication of rheumatoid arthritis with autoimmune NEUTROPENIA; and SPLENOMEGALY.
A synthetic analog of LYPRESSIN with a PHENYLALANINE substitution at residue 2. Felypressin is a vasoconstrictor with reduced antidiuretic activity.
A disorder characterized by a recurrent or persistent inability to attain or maintain until completion of sexual activity an adequate physical response of sexual excitement, consisting of vasocongestion in the pelvis, vaginal lubrication and expansion, and swelling of the external genitalia.
Development of female secondary SEX CHARACTERISTICS in the MALE. It is due to the effects of estrogenic metabolites of precursors from endogenous or exogenous sources, such as ADRENAL GLANDS or therapeutic drugs.
New abnormal growth of tissue in the FEMUR.
Aseptic or avascular necrosis of the femoral head. The major types are idiopathic (primary), as a complication of fractures or dislocations, and LEGG-CALVE-PERTHES DISEASE.
The hydrochloride salt form of nefopam, a centrally-acting, non-opioid benzoxazocine with analgesic activity. The mechanism of action through which nefopam exerts its analgesic effects is, as of yet, largely unknown but may involve inhibition of serotonin, dopamine and noradrenaline reuptake.
Antinematodal benzimidazole used in veterinary medicine.
Coronary vasodilator; inhibits calcium function in muscle cells in excitation-contraction coupling; proposed as antiarrhythmic and antianginal agents.
A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release.
A propionic acid derivative that is used as a non-steroidal anti-inflammatory agent.
A short-acting sympathomimetic agent with bronchodilator activity. Fenoterol stimulates beta-2-adrenergic receptors in the lungs, thereby activating the enzyme adenylate cyclase that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP concentrations relax bronchial smooth muscle, relieve bronchospasms, and reduce inflammatory cell mediator release, especially from mast cells.
A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)
Anaerobic degradation of GLUCOSE or other organic nutrients to gain energy in the form of ATP. End products vary depending on organisms, substrates, and enzymatic pathways. Common fermentation products include ETHANOL and LACTIC ACID.
An iron protein complex, containing up to 23% iron, formed by the union of ferric iron with apoferritin; it is found in the intestinal mucosa, spleen, bone marrow, reticulocytes, and liver, and regulates iron storage and transport from the intestinal lumen to plasma.
Drugs used to increase fertility or to treat infertility.
Compounds which increase the capacity to conceive in females.
Compounds which increase the capacity of the male to induce conception.
A condition occurring in FETUS or NEWBORN due to in utero ETHANOL exposure when mother consumed alcohol during pregnancy. It is characterized by a cluster of irreversible BIRTH DEFECTS including abnormalities in physical, mental, and behavior development (such as FETAL GROWTH RETARDATION; MENTAL RETARDATION; ATTENTION DEFICIT AND DISRUPTIVE BEHAVIOR DISORDERS) with varied degree of severity in an individual.
Death of a fetus after 10 weeks gestation.
A non-neoplastic or neoplastic disorder which occurs in the fetus.
A nonreassuring fetal status (NRFS) indicating that the FETUS is compromised (American College of Obstetricians and Gynecologists 1988). It can be identified by sub-optimal values in FETAL HEART RATE; oxygenation of FETAL BLOOD; and other parameters.
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age. [HPO:probinson]
A condition of fetal overgrowth leading to a large-for-gestational-age FETUS. It is defined as BIRTH WEIGHT greater than 4,000 grams or above the 90th percentile for population and sex-specific growth curves. It is commonly seen in GESTATIONAL DIABETES; PROLONGED PREGNANCY; and pregnancies complicated by pre-existing diabetes mellitus.
Premature rupture of membranes (PROM) is a condition which occurs in pregnancy when the amniotic sac ruptures more than an hour before the onset of labor.
The disintegration and assimilation of the dead FETUS in the UTERUS at any stage after the completion of organogenesis which, in humans, is after the 9th week of GESTATION. It does not include embryo resorption (see EMBRYO LOSS).
A condition in which inanimate objects are utilized as a preferred or exclusive method of stimulating erotic arousal.
Loss of fetal blood into the maternal circulation.
A condition characterized by an abnormally high body temperature. In a hyperthermic state, the hypothalamic set-point is normal but body temperature increases and overrides the ability to lose heat, resulting from exogenous heat exposure or endogenous heat production.
A febrile process with an etiology that is not apparent or yet determined.
A class of interferon elaborated by fibroblasts.
A glycosylated elastic protein produced by the cleavage of fibrinogen by the protease thrombin during blood coagulation.
A fibrillar protein present in blood plasma; it converts to fibrin during the process of blood clot formation.
A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.
Any agent capable of dissolving an existing blood clot in order to reperfuse the blocked blood vessel.
A common and benign breast disease characterized by varying degree of fibrocystic changes in the breast tissue. There are three major patterns of morphological changes, including FIBROSIS, formation of CYSTS, and proliferation of glandular tissue (adenosis). The fibrocystic breast has a dense irregular, lumpy, bumpy consistency.
Fibrodysplasia ossificans progressiva is a rare autosomal dominant disease with complete penetrance involving progressive ossification of skeletal muscle, fascia, tendons, and ligaments. FOP has a prevalence of approximately 1 in 2 million worldwide, and shows no geographic, ethnic, racial, or gender preference. Individuals with FOP appear normal at birth except for great toe abnormalities: the great toes are short, deviated, and monophalangic. Ossification occurs progressively over the course of a lifetime in an inevitable and unpredictable episodic manner, with most patients being confined to a wheelchair by the third decade of life and requiring lifelong care (summary by Petrie et al., 2009).
A benign tumor of fibrous or fully developed connective tissue.
A poorly circumscribed neoplasm arising from the soft tissues. It is characterized by the presence of spindle-shaped fibroblasts and an infiltrative growth pattern.
Generalized or localized diffuse fibrous overgrowth of the gingival tissue, usually transmitted as an autosomal dominant trait, but some cases are idiopathic and others produced by drugs. The enlarged gingiva is pink, firm, and has a leather-like consistency with a minutely pebbled surface and in severe cases the teeth are almost completely covered and the enlargement projects into the oral vestibule. (Dorland, 28th ed)
Fibromuscular dysplasia (FMDA) is a nonatherosclerotic, noninflammatory arterial disease that most commonly involves the renal and carotid arteries. The prevalence of symptomatic renal artery FMDA is about 4 in 1,000 and the prevalence of cervicocranial FMDA is about half of that. Histologic classification includes 3 main subtypes, intimal, medial, and perimedial, which may be associated in a single patient. Angiographic classification includes the multifocal type, with multiple stenoses and the 'string of beads' appearance that is related to medial FMDA, and tubular and focal types, which are not clearly related to specific histologic lesions (summary by Plouin et al., 2007)
A chronic disorder of unknown etiology characterized by pain, stiffness, and tenderness in the muscles of neck, shoulders, back, hips, arms, and legs. Other signs and symptoms include headaches, fatigue, sleep disturbances, and painful menstruation.
A fibroblastic sarcoma is a malignant tumor derived from fibrous connective tissue and characterized by immature proliferating fibroblasts or undifferentiated anaplastic spindle cells.
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.
A disease of bone marked by thinning of the cortex by fibrous tissue containing bony spicules, producing pain, disability, and gradually increasing deformity. Only one bone may be involved (FIBROUS DYSPLASIA, MONOSTOTIC) or several (FIBROUS DYSPLASIA, POLYOSTOTIC).
FIBROUS DYSPLASIA OF BONE involving only one bone.
FIBROUS DYSPLASIA OF BONE affecting several bones. When melanotic pigmentation (CAFE-AU-LAIT SPOTS) and multiple endocrine hyperfunction are additionally associated it is referred to as Albright syndrome.
A furocoumarin that intercalates with DNA, inhibiting DNA synthesis and cell division. Psoralen is used in Photochemotherapy with high-intensity long-wavelength UVA irradiation. Psoralens are tricyclic furocumarins and have a strong tendency to intercalate with DNA base pairs. Irradiation of nucleic acids in the presence of psoralen with long wave UV (~360 nm) results in the 2+2 cyclo- addition of either of its two photoreactive sites with 5,6-carbon bonds of pyrimidines resulting in crosslinking double-stranded nucleic acids.
An infection that is caused by the organism Mansonella ozzardi.
Pharmacological agents destructive to nematodes in the superfamily Filarioidea.
Diseases of freshwater, marine, hatchery or aquarium fish. This term includes diseases of both teleosts (true fish) and elasmobranchs (sharks, rays and skates).
The oil extracted from fish such as cod, salmon, and shark. Fish liver oils typically contain high levels of omega-3 fatty acids, EPA and DHA, and vitamins A and D. It is used as a dietary supplement.
An oil derived from the tissues of oily fish. Fish oil is considered valuable due to its high content of omega-3 fatty acids eicosapentanoic acid and docosahexaenoic acid. Such fatty acids are not actually produced in fish, but are accumulated from phytoplankton which produce omega-3 fatty acids.
A painful linear ulcer at the margin of the anus. It appears as a crack or slit in the mucous membrane of the anus and is very painful and difficult to heal. (Dorland, 27th ed & Stedman, 25th ed)
Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body.
An abnormal connection between the intestine and another epithelial-lined structure, but that does not include the rectum or anus.
An inhibitor of the last step of noradrenaline biosynthesis.
A complication of multiple RIB FRACTURES; RIB and STERNUM fractures, or thoracic surgery. A portion of the THORACIC WALL becomes isolated from the RIB CAGE and exhibits paradoxical respiration.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the flank.
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
A drug that has been used in various urinary syndromes and as an antispasmodic. Its therapeutic usefulness and its mechanism of action are not clear. It may have local anesthetic activity and direct relaxing effects on smooth muscle as well as some activity as a muscarinic antagonist.
A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.
Deposits of various size, shape, consistency, refractive index, and motility within the eye's vitreous humour, which is normally transparent. [HPO:sdoelken]
A synthetic triazole with antifungal activity. Fluconazole preferentially inhibits fungal cytochrome P-450 sterol C-14 alpha-demethylation, resulting in the accumulation of fungal 14 alpha-methyl sterols, the loss of normal fungal sterols, and fungistatic activity. Mammalian cell demethylation is much less sensitive to fluconazole inhibition.
A fluorinated cytosine analog that is used as an antifungal agent.
A synthetic corticosteroid with antiinflammatory and antiallergic properties. Fludrocortisone is a mineralocorticoid receptor and glucocorticoid receptor agonist that binds to cytoplasmic receptors, translocates to the nucleus and subsequently initiates the transcription of glucocorticoid-responsive genes such as lipocortins to inhibit phospholipase A2. This prevents the release of arachidonic acid, a precursor to prostaglandins and leukotrienes, both important mediators in the pro-inflammatory response mechanism. In addition, this agent exerts its mineralocorticoid effect on the distal tubules and collecting ducts of the kidney by inducing permease, an enzyme that regulates Na+ permeability in cells, thereby enhancing Na+ reabsorption and water retention as well as increasing K+, H+ excretion.
An anthranilic acid derivative with analgesic, anti-inflammatory, and antipyretic properties. It is used in musculoskeletal and joint disorders and administered by mouth and topically. (From Martindale, The Extra Pharmacopoeia, 30th ed, p16)
A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.
An anti-inflammatory glucocorticoid used in veterinary practice.
Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy.
A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug.
A glucocorticoid derivative used topically in the treatment of various skin disorders. It is usually employed as a cream, gel, lotion, or ointment. It has also been used topically in the treatment of inflammatory eye, ear, and nose disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p732)
A synthetic glucocorticoid and derivative of fluocinolone acetonide with anti-inflammatory and antipruritic activities. Fluocinonide binds the glucocorticoid receptor, followed by translocation of the ligand-receptor complex to the nucleus and transcription activation of genes containing glucocorticoid-responsive elements. Lipocortin-1 is one factor induced by fluocinonide that interacts and inhibits cytosolic phospholipase 2 alpha, thereby preventing phospholipase translocation to the perinuclear membrane and subsequent release and conversion of arachidonic acid to inflammatory prostaglandins. In addition, MAPK phosphatase 1 is induced, thereby preventing the triggering of the MAPK cascade resulting in pro-inflammatory effects via Jun N-terminal kinase and c-Jun. Finally, fluocinonide binds to and inhibits nuclear factor kappa-B directly, resulting in inhibition of cyclooxygenase 2 transcription and subsequent prostaglandin synthesis.
A glucocorticoid with anti-inflammatory activity used topically for various skin disorders.
Considered a trace element, fluoride is any combination of elements containing the fluorine atom in the -1 oxidation state (fluoride ion). Due to its reactivity, fluorine is found in nature as fluorine compounds or fluorides. Fluoride inhibits various enzyme systems, erythrocyte glycolysis and binds Ca++, causing anticoagulation and other toxic effects. In addition, fluoride is a mitogen for osteoblasts and stimulates bone formation. (NCI)
A fluorinated pyrimidine monophosphate analogue of 5-fluoro-2'-deoxyuridine-5'-phosphate (FUDR-MP) with antineoplastic activity. As an antimetabolite, floxuridine inhibits thymidylate synthase, resulting in disruption of DNA synthesis and cytotoxicity. This agent is also metabolized to fluorouracil and other metabolites that can be incorporated into RNA and inhibit the utilization of preformed uracil in RNA synthesis. (NCI04)
5-Fluoro-2'-deoxyuridylate. An inhibitor of thymidylate synthetase. Formed from 5-fluorouracil or 5-fluorodeoxyuridine.
A glucocorticoid employed, usually as eye drops, in the treatment of allergic and inflammatory conditions of the eye. It has also been used topically in the treatment of various skin disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p732)
A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.
The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.
A halogenated derivative of 17-alpha-methyltestosterone. Similar to testosterone, fluoxymesterone binds to and activates specific nuclear receptors, resulting in an increase in protein anabolism, a decrease in amino acid catabolism, and retention of nitrogen, potassium, and phosphorus. This agent also may competitively inhibit prolactin receptors and estrogen receptors, thereby inhibiting the growth of hormone-dependent tumor lines. Fluoxymesterone is approximately five times more potent than methyltestosterone. (NCI04)
A thioxanthene neuroleptic that, unlike CHLORPROMAZINE, is claimed to have CNS-activating properties. It is used in the treatment of psychoses although not in excited or manic patients. (From Martindale, The Extra Pharmacopoeia, 30th ed, p595)
A phenothiazine used in the treatment of PSYCHOSES. Its properties and uses are generally similar to those of CHLORPROMAZINE.
A synthetic glucocorticoid with anti-inflammatory properties.
A corticosteroid used topically in the treatment of various skin disorders. It is usually employed as a cream or an ointment, and is also used as a polyethylene tape with an adhesive. (From Martindale, The Extra Pharmacopoeia, 30th ed, p733)
A benzodiazepine derivative used mainly as a hypnotic.
A derivative of propionic acid, and a phenylalkanoic acid derivative of non-steroidal antiinflammatory drugs (NSAIDs) with analgesic, antiinflammatory and antipyretic effects. Flurbiprofen non-selectively binds to and inhibits cyclooxygenase (COX). This results in a reduction of arachidonic acid conversion into prostaglandins that are involved in the regulation of pain, inflammation and fever. This NSAID also inhibits carbonic anhydrase, thereby reducing the production of hydrogen and bicarbonate ions. Upon ocular administration, flurbiprofen may reduce bicarbonate ion concentrations leading to a decrease in the production of aqueous humor, thereby lowering intraocular pressure.
A convulsant primarily used in experimental animals. It was formerly used to induce convulsions as a alternative to electroshock therapy.
A transient reddening of the face that may be due to fever, certain drugs, exertion, or stress.
A long-acting injectable antipsychotic agent used for chronic schizophrenia.
A toluidine derivative and a nonsteroidal antiandrogen that is structurally related to bicalutamide and nilutamide. Flutamide and its more potent active metabolite 2-hydroxyflutamide competitively block dihydrotestosterone binding at androgen receptors, forming inactive complexes which cannot translocate into the cell nucleus. Formation of inactive receptors inhibits androgen-dependent DNA and protein synthesis, resulting in tumor cell growth arrest or transient tumor regression. (NCI04)
A coenzyme for a number of oxidative enzymes including NADH DEHYDROGENASE. It is the principal form in which RIBOFLAVIN is found in cells and tissues.
Focal dermal hypoplasia is a multisystem disorder characterized primarily by involvement of the skin, skeletal system, eyes, and face. Skin manifestations present at birth include atrophic and hypoplastic areas of skin; cutis aplasia; fat nodules in the dermis manifesting as soft, yellow-pink cutaneous nodules; and pigmentary changes. Verrucoid papillomas of the skin and mucous membranes may appear later. The nails can be ridged, dysplastic, or hypoplastic; hair can be sparse or absent. Limb malformations include oligo-/syndactyly and split hand/foot. Developmental abnormalities of the eye can include anophthalmia/microphthalmia, iris and chorioretinal coloboma, and lacrimal duct abnormalities. Craniofacial findings can include facial asymmetry, notched alae nasi, cleft lip and palate, and pointed chin. Occasional findings include dental anomalies, abdominal wall defects, diaphragmatic hernia, and renal anomalies. Psychomotor development is usually normal; some individuals have cognitive impairment.
An infection at a specific location that may spread to another region of the body.
Secondary or systemic infections due to dissemination throughout the body of microorganisms whose primary focus of infection lies in the periodontal tissues.
A disorder characterized by recurrent localized paroxysmal discharges of cerebral neurons that give rise to seizures that have motor manifestations. The majority of partial motor seizures originate in the FRONTAL LOBE (see also EPILEPSY, FRONTAL LOBE). Motor seizures may manifest as tonic or clonic movements involving the face, one limb or one side of the body. A variety of more complex patterns of movement, including abnormal posturing of extremities, may also occur.
A collective term for pteroylglutamic acids and their oligoglutamic acid conjugates. As a natural water-soluble substance, folic acid is involved in carbon transfer reactions of amino acid metabolism, in addition to purine and pyrimidine synthesis, and is essential for hematopoiesis and red blood cell production. (NCI05)
A compound with a chemical structure similar to folic acid. Folate antagonists inhibit one or more folate-dependent enzymes, resulting in decreased DNA, RNA and protein synthesis.
A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed)
A benign ovarian cyst that develops from a persistent, unruptured Graafian follicle, which grows larger than three centimeters.
Inflammation of follicles, primarily hair follicles.
Gastrointestinal disturbances, skin eruptions, or shock due to allergic reactions to allergens in food.
Alterations or deviations from normal shape or size which result in a disfigurement of the foot.
Alterations or deviations from normal shape or size which result in a disfigurement of the foot occurring at or before birth.
Skin diseases of the foot, general or unspecified.
Anatomical and functional disorders affecting the foot.
A sensation of discomfort emanating from the foot, its supporting structures, or its articulation with the ankle.
A disease of the horny parts and of the adjacent soft structures of the feet of cattle, swine, and sheep. It is usually caused by Corynebacterium pyogenes or Bacteroides nodosus (see DICHELOBACTER NODOSUS). It is also known as interdigital necrobacillosis. (From Black's Veterinary Dictionary, 18th ed)
A highly infectious disease caused by FOOT AND MOUTH DISEASE VIRUS that affects mammals of the ARTIODACTYLA order (CATTLE; SHEEP; GOATS; and PIGS) and is characterized by high fever followed by the appearance of blisters inside the mouth and on the feet.
A condition in which the FORAMEN OVALE in the ATRIAL SEPTUM fails to close shortly after birth. This results in abnormal communications between the two upper chambers of the heart. An isolated patent ovale foramen without other structural heart defects is usually of no hemodynamic significance.
The rate of airflow measured during a FORCED VITAL CAPACITY determination.
An inflammatory lesion in the muscle comprised of epithelioid histiocytes and chronic inflammation that is caused by the presence of extraneous material .
A granulomatous inflammatory reaction evoked by the presence of an exogenous material in the tissues, a characteristic feature of which is the formation of foreign body giant cells.
A colorless poisonous gas synthesized by the oxidation of methanol and used as an antiseptic, disinfectant, histologic fixative, and general-purpose chemical reagent for laboratory applications. Formaldehyde is readily soluble in water and is commonly distributed as a 37% solution in water; formalin, a 10% solution of formaldehyde in water, is used as a disinfectant and to preserve biological specimens. Environmentally, formaldehyde may be found in the atmosphere, smoke from fires, automobile exhaust and cigarette smoke. Small amounts are produced during normal metabolic processes in most organisms, including humans.
Subjective cutaneous sensations of insects in the absence of stimulation.
Pyrazolopyrimidine ribonucleosides isolated from Nocardia interforma. They are antineoplastic antibiotics with cytostatic properties.
A sodium salt formulation of phosphonoacetic acid with activity against herpes simplex viruses and other members of the herpes virus family. Fosfonet inhibits viral DNA polymerase and inhibits the synthesis of viral DNA.
Infection of domestic and wild fowl and other BIRDS with INFLUENZA A VIRUS. Avian influenza usually does not sicken birds, but can be highly pathogenic and fatal in domestic POULTRY.
A poxvirus infection of poultry and other birds characterized by the formation of wart-like nodules on the skin and diphtheritic necrotic masses (cankers) in the upper digestive and respiratory tracts.
A chronic inflammatory skin disorder characterized by pruritic papular eruptions in areas with apocrine glands. It usually affects the axillae bilaterally. There is rupture of the apocrine ducts resulting in inflammation and formation of the papular skin lesions.
A pathologic fracture occurs when a bone breaks in an area that is weakened secondary to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
A fracture in which union fails to occur, the ends of the bone becoming rounded and eburnated, and a false joint occurs. (Stedman, 25th ed)
FMR1-related disorders include fragile X syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), and FMR1-related primary ovarian insufficiency (POI). Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function variant and is nearly always characterized by moderate intellectual disability in affected males and mild intellectual disability in affected females. Because FMR1 pathogenic variants are complex alterations involving non-classic gene-disrupting alterations (trinucleotide repeat expansion) and abnormal gene methylation, affected individuals occasionally have an atypical presentation with an IQ above 70, the traditional demarcation denoting intellectual disability (previously referred to as mental retardation). Males with an FMR1 full mutation accompanied by aberrant methylation may have a characteristic appearance (large head, long face, prominent forehead and chin, protruding ears), connective tissue findings (joint laxity), and large testes after puberty. Behavioral abnormalities, sometimes including autism spectrum disorder, are common. FXTAS occurs in males (and some females) who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor. FMR1-related POI (age at cessation of menses <40 years) occurs in approximately 20% of females who have an FMR1 premutation.
The presence of an increased number of freckles, small circular spots on the skin that are darker than the surrounding skin because of deposits of melanin.
A condition occurring in the female offspring of dizygotic twins (TWIN, DIZYGOTIC) in a mixed-sex pregnancy, usually in CATTLE. Freemartinism can occur in other mammals. When placental fusion between the male and the female FETUSES permits the exchange of fetal cells and fetal hormones, TESTICULAR HORMONES from the male fetus can androgenize the female fetus producing a sterile XX/XY chimeric ""female""(CHIMERISM).
An antigen solution emulsified in mineral oil. The complete form is made up of killed, dried mycobacteria, usually M. tuberculosis, suspended in the oil phase. It is effective in stimulating cell-mediated immunity (IMMUNITY, CELLULAR) and potentiates the production of certain IMMUNOGLOBULINS in some animals. The incomplete form does not contain mycobacteria.
Friedreich ataxia (FRDA) is characterized by slowly progressive ataxia with onset usually before age 25 years (mean age at onset: 10-15 yrs). FRDA is typically associated with dysarthria, muscle weakness, spasticity particularly in the lower limbs, scoliosis, bladder dysfunction, absent lower limb reflexes, and loss of position and vibration sense. Approximately two thirds of individuals with FRDA have cardiomyopathy, up to 30% have diabetes mellitus, and approximately 25% have an ""atypical"" presentation with later onset or retained tendon reflexes.
A rare acquired endocrine disorder more commonly affecting males. It is caused by lesions in the hypothalamus. Clinical signs include obesity, short stature, pubertal delay, hypogonadism, visual impairment, polydipsia and polyuria.
An acute or chronic inflammatory process affecting the mucous membrane of the frontal sinus.
A disorder characterized by recurrent sexual urges, fantasies, or behaviors involving touching the genitals of or rubbing the genitals against a nonconsenting person.
A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding.
Following dietary exposure to fructose, sucrose, or sorbitol, untreated hereditary fructose intolerance (HFI) is characterized by metabolic disturbances (hypoglycemia, lactic acidemia, hypophosphatemia, hyperuricemia, hypermagnesemia, hyperalaninemia) and clinical findings (nausea, vomiting, and abdominal distress; chronic growth restriction/failure to thrive). Untreated HFI typically first manifests when fructose- and sucrose-containing foods are introduced in the course of weaning young infants from breast milk. If large quantities of fructose are ingested, the infant may acutely develop lethargy, seizures, and/or progressive coma. Untreated HFI may result in renal and hepatic failure. If identified and treated before permanent organ injury occurs, individuals with HFI can experience a normal quality of life and life expectancy.
Inherited abnormalities of fructose metabolism, which include three known autosomal recessive types: hepatic fructokinase deficiency (essential fructosuria), hereditary fructose intolerance, and hereditary fructose-1,6-diphosphatase deficiency. Essential fructosuria is a benign asymptomatic metabolic disorder caused by deficiency in fructokinase, leading to decreased conversion of fructose to fructose-1-phosphate and alimentary hyperfructosemia, but with no clinical dysfunction; may produce a false-positive diabetes test.
Fructose-1,6-bisphosphatase deficiency is an autosomal recessive disorder characterized by impaired gluconeogenesis. Patients present with hypoglycemia and metabolic acidosis on fasting and may have episodes of hyperventilation, apnea, hypoglycemia, and ketosis. Although the disorder may be lethal in the newborn period, proper treatment yields an excellent prognosis (Kikawa et al., 1997; Matsuura et al., 2002).
A major gonadotropin secreted by the human adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and the LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. The alpha subunit is common in the three human pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
A congener of the antimetabolite fluorouracil with antineoplastic activity. Tegafur is a prodrug that is gradually converted to fluorouracil in the liver by the cytochrome P-450 enzyme. Subsequently, 5-FU is metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP) by both tumor cells and normal cells. FdUMP inhibits DNA synthesis and cell division by inhibiting thymidylate synthase and reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate. (NCI04)
An autosomal dominant, bilateral, slowly progressive degeneration of corneal endothelial cells with thickening of Descemet's membrane and accumulation of excrescences. It results in corneal edema and loss of vision.
Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase with accumulation of fucose in the tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex. Fucosidosis has been classified into 2 major types. Type 1 is characterized by rapid psychomotor regression and severe neurologic deterioration beginning at about 6 months of age, elevated sweat sodium chloride, and death within the first decade of life. Type 2 is characterized by milder psychomotor retardation and neurologic signs, the development of angiokeratoma corporis diffusum, normal sweat salinity, and longer survival (Kousseff et al., 1976).
Involuntary urine release that cannot be attributed to an anatomic or physiologic etiology.
The volume of air remaining in the LUNGS at the end of a normal, quiet expiration. It is the sum of the RESIDUAL VOLUME and the EXPIRATORY RESERVE VOLUME. Common abbreviation is FRC.
Suspensions of attenuated or killed fungi administered for the prevention or treatment of infectious fungal disease.
A developmental anomaly in which the lower sternum is posteriorly dislocated and concavely deformed, resulting in a funnel-shaped thorax.
Nitrofuran derivative anti-infective agent used for urinary tract infections.
A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.
A nutritional supplement and vitamin B1 derivative, with potential antineoplastic activity. Upon oral administration, fursultiamine inhibits the expressions of octamer-binding transcription factor 4 (OCT-4), SRY (sex determining region Y)-box 2 (SOX-2), and Nanog homeobox (NANOG) in cancer stem cells (CSCs). This may inhibit the proliferation of CSCs thereby preventing tumor cell growth. In addition, fursultiamine inhibits the expression of ATP-binding cassette (ABC) transporters subfamily B member 1 (ABCB1) and subfamily G member 2 (ABCG2) in cancer CSCs, which may abrogate resistance to chemo- and radiotherapy in CSCs. CSCs promote tumor initiation, progression and metastasis; they play a key role in cancer recurrence and resistance to chemotherapy and radiation.
A persistent skin infection marked by the presence of furuncles, often chronic and recurrent. In humans, the causative agent is various species of STAPHYLOCOCCUS. In salmonid fish (SALMONIDS), the pathogen is AEROMONAS SALMONICIDA.
A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits DOPAMINE BETA-HYDROXYLASE, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis.
A dental anomaly characterized by the presence of a two fused teeth.
Infection with anaerobic gram-negative bacteria of the genus Fusobacterium. It results in abscess formation and tissue damage.
A glycosphingolipid containing a sialic acid residue found in neuronal cell membranes, with potential neuroprotective and neuroregenerative activities. Upon administration, monosialotetrahexosylganglioside, also called GM-1, is able to both prevent neurologic damage and induce regeneration of damaged neurons through neurotrophic repair mechanisms, enhancement of the production of neutrophins, and augmenting neurite outgrowth. In addition, GM-1 exerts anti-excitotoxic activity, prevents necrosis, and improves neuronal recovery and function.
Contraction of the muscle of the PHARYNX caused by stimulation of sensory receptors on the SOFT PALATE, by psychic stimuli, or systemically by drugs.
A pattern or manner of running, walking, or moving on foot.
The term galactosemia refers to disorders of galactose metabolism that include classic galactosemia, clinical variant galactosemia, and biochemical variant galactosemia. This GeneReview focuses on: Classic galactosemia, which can result in life-threatening complications including feeding problems, failure to thrive, hepatocellular damage, bleeding, and E. coli sepsis in untreated infants. If a lactose-restricted diet is provided during the first ten days of life, the neonatal signs usually quickly resolve and the complications of liver failure, sepsis, and neonatal death are prevented; however, despite adequate treatment from an early age, children with classic galactosemia remain at increased risk for developmental delays, speech problems (termed childhood apraxia of speech and dysarthria), and abnormalities of motor function. Almost all females with classic galactosemia manifest premature ovarian insufficiency (POI). Clinical variant galactosemia, which can result in life-threatening complications including feeding problems, failure to thrive, hepatocellular damage including cirrhosis and bleeding in untreated infants. This is exemplified by the disease that occurs in African Americans and native Africans in South Africa. Persons with clinical variant galactosemia may be missed with newborn screening (NBS) as the hypergalactosemia is not as marked as in classic galactosemia and breath testing is normal. If a lactose-restricted diet is provided during the first ten days of life, the severe acute neonatal complications are usually prevented. African Americans with clinical variant galactosemia and adequate early treatment do not appear to be at risk for long-term complications including POI.
A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.
A synthetic nondepolarizing blocking drug. The actions of gallamine triethiodide are similar to those of TUBOCURARINE, but this agent blocks the cardiac vagus and may cause sinus tachycardia and, occasionally, hypertension and increased cardiac output. It should be used cautiously in patients at risk from increased heart rate but may be preferred for patients with bradycardia. (From AMA Drug Evaluations Annual, 1992, p198)
A non-neoplastic or neoplastic disorder that affects the gallbladder. Representative examples of non-neoplastic disorders include acute and chronic cholecystitis, often associated with the presence of gallstones. Representative examples of neoplastic disorders include adenoma, carcinoma, lymphoma, and sarcoma.
A benign or malignant neoplasm affecting the gallbladder. Representative examples of benign neoplasms include lipoma, leiomyoma, and neurofibroma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma.
Coronary vasodilator that is an analog of iproveratril (VERAPAMIL) with one more methoxy group on the benzene ring.
An 11-amino acid peptide derived from the N-terminal fragment of pro-opiomelanocortin (POMC). Gamma-MSH stimulates adrenal steroidogenesis and has an regulatory role in the cardiovascular and the renal systems.
A natural tocopherol with less antioxidant activity than ALPHA-TOCOPHEROL. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. As in BETA-TOCOPHEROL, it also has three methyl groups on the 6-chromanol nucleus but at different sites.
The 11-residue peptide that is fully amidated.
The 11-residue peptide plus the 12-residue sequence leading to the next dibasic cleavage site at the N-terminal of the joining peptide.
A synthetic guanine derivative with antiviral activity. As the active metabolite of ganciclovir, ganciclovir-5-triphosphate (ganciclovir-TP) appears to inhibit viral DNA synthesis by competitive inhibition of viral DNA polymerases and incorporation into viral DNA, resulting in eventual termination of viral DNA elongation.
A benign neoplasm that usually arises from the sympathetic trunk in the mediastinum, representing a tumor of the sympathetic nerve fibers arising from neural crest cells.
Agents that mimic neural transmission by stimulation of the nicotinic receptors on postganglionic autonomic neurons. Drugs that indirectly augment ganglionic transmission by increasing the release or slowing the breakdown of acetylcholine or by non-nicotinic effects on postganglionic neurons are not included here nor are the nonspecific cholinergic agonists.
A subclass of ACIDIC GLYCOSPHINGOLIPIDS. They contain one or more sialic acid (N-ACETYLNEURAMINIC ACID) residues. Using the Svennerholm system of abbrevations, gangliosides are designated G for ganglioside, plus subscript M, D, or T for mono-, di-, or trisialo, respectively, the subscript letter being followed by a subscript arabic numeral to indicated sequence of migration in thin-layer chromatograms. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1997)
A group of autosomal recessive lysosomal storage disorders marked by the accumulation of GANGLIOSIDES. They are caused by impaired enzymes or defective cofactors required for normal ganglioside degradation in the LYSOSOMES. Gangliosidoses are classified by the specific ganglioside accumulated in the defective degradation pathway.
A serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies (necrosis).
A variant of ADENOMATOUS POLYPOSIS COLI caused by mutation in the APC gene (GENES, APC) on CHROMOSOME 5. It is characterized by not only the presence of multiple colonic polyposis but also extracolonic ADENOMATOUS POLYPS in the UPPER GASTROINTESTINAL TRACT; the EYE; the SKIN; the SKULL; and the FACIAL BONES; as well as malignancy in organs other than the GI tract.
A severe condition resulting from bacteria invading healthy muscle from adjacent traumatized muscle or soft tissue. The infection originates in a wound contaminated with bacteria of the genus CLOSTRIDIUM. C. perfringens accounts for the majority of cases (over eighty percent), while C. noyvi, C. septicum, and C. histolyticum cause most of the other cases.
Abnormal passage communicating with the STOMACH.
A gastrointestinal peptide hormone of about 43-amino acids. It is found to be a potent stimulator of INSULIN secretion and a relatively poor inhibitor of GASTRIC ACID secretion.
Extreme dilation of the submucusoal veins in the stomach.
A gastrin-producing neuroendocrine tumor. It is usually located in the pancreas but it is also found at other anatomic sites, including the stomach and small intestine.
Inflammation of the GASTRIC MUCOSA, a lesion observed in a number of unrelated disorders.
A form of chronic gastritis associated with atrophic gastric mucous membrane.
A type of gastritis characterized by excessive proliferation of the gastric mucosa and diffuse thickening of the gastric mucosal folds.
An inflammatory disorder that affects the upper and lower gastrointestinal tract. Most commonly, this is attributed to viruses; however bacteria, parasites or adverse reactions can also be the culprit. Symptoms include acute diarrhea and vomiting.
A condition of chronic gastroenteritis in adult pigs and fatal gastroenteritis in piglets caused by a CORONAVIRUS.
Gastroesophageal reflux (GER) is characterized by the retrograde movement of stomach contents into the esophagus. In its most severe form, GER results in extensive tissue damage caused by acid reflux. In adolescents and adults, and even infrequently in children, chronic GER is associated with the risk of developing Barrett metaplasia (614266), a premalignant lesion of the esophageal mucosa (Hu et al., 2000). In turn, Barrett metaplasia is correlated with the development of adenocarcinoma of the esophagus (see 614266), estimated as the fifth most prevalent neoplasia in the Western world (Lagergren et al., 1999).
Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion.
A non-neoplastic or neoplastic disorder that affects the gastrointestinal tract, anus, liver, biliary system, and pancreas.
Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.
A dysfunction in gastrointestinal function that is due to a psychological process.
A benign or malignant neoplasm involving any part of the digestive system.
Gaucher disease (GD) encompasses a continuum of clinical findings from a perinatal lethal disorder to an asymptomatic type. The identification of three major clinical types (1, 2, and 3) and two other subtypes (perinatal-lethal and cardiovascular) is useful in determining prognosis and management. GD type 1 is characterized by the presence of clinical or radiographic evidence of bone disease (osteopenia, focal lytic or sclerotic lesions, and osteonecrosis), hepatosplenomegaly, anemia and thrombocytopenia, lung disease, and the absence of primary central nervous system disease. GD types 2 and 3 are characterized by the presence of primary neurologic disease; in the past, they were distinguished by age of onset and rate of disease progression, but these distinctions are not absolute. Disease with onset before age two years, limited psychomotor development, and a rapidly progressive course with death by age two to four years is classified as GD type 2. Individuals with GD type 3 may have onset before age two years, but often have a more slowly progressive course, with survival into the third or fourth decade. The perinatal-lethal form is associated with ichthyosiform or collodion skin abnormalities or with nonimmune hydrops fetalis. The cardiovascular form is characterized by calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and supranuclear ophthalmoplegia. Cardiopulmonary complications have been described with all the clinical subtypes, although varying in frequency and severity.
A water insoluble terpene fatty acid used in the treatment of gastrointestinal ulcers; it facilitates the healing and function of mucosal tissue.
A product formed from skin, white connective tissue, or bone COLLAGEN. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories.
A fibric acid derivative with hypolipidemic effects. Gemfibrozil interacts with peroxisome proliferator-activated receptors (PPARalpha) resulting in PPARalpha-mediated stimulation of fatty acid oxidation and an increase in lipoprotein lipase (LPL) synthesis. This enhances triglyceride-rich lipoprotein clearance and reduces the expression of apolipoprotein C-III (apoC-III). The reduction in hepatic production of apoC-III results in subsequent reduction of serum levels of very-low-density-lipoprotein cholesterol (VLDL-C). In addition, gemfibrozil-mediated PPARalpha stimulation of apoA-I and apoA-II expression results in an increase in high-density lipoprotein cholesterol (HDL-C).
A disorder characterized by a strong and persistent cross-gender identification (such as stating a desire to be the other sex or frequently passing as the other sex) coupled with persistent discomfort with his or her sex (manifested in adults, for example, as a preoccupation with altering primary and secondary sex characteristics through hormonal manipulation or surgery).
Agents that induce various degrees of analgesia; depression of consciousness, circulation, and respiration; relaxation of skeletal muscle; reduction of reflex activity; and amnesia. There are two types of general anesthetics, inhalation and intravenous. With either type, the arterial concentration of drug required to induce anesthesia varies with the condition of the patient, the desired depth of anesthesia, and the concomitant use of other drugs. (From AMA Drug Evaluations Annual, 1994, p.173)
An abnormality of leucocytes, the cause of which is present from birth.
A syndrome characterized by facial palsy in association with a herpetic eruption of the external auditory meatus. This may occasionally be associated with tinnitus, vertigo, deafness, severe otalgia, and inflammation of the pinna. The condition is caused by reactivation of a latent HERPESVIRUS 3, HUMAN infection which causes inflammation of the facial and vestibular nerves, and may occasionally involve additional cranial nerves. (From Adams et al., Principles of Neurology, 6th ed, p757)
Pathological processes involving the female reproductive tract (GENITALIA, FEMALE).
Pathological processes involving the male reproductive tract (GENITALIA, MALE).
A benign, precancerous, or malignant neoplasm that affects the female reproductive system. Representative examples include uterine corpus leiomyoma, endocervical polyp, ovarian carcinoma, cervical carcinoma, and endometrial carcinoma.
A benign, borderline, or malignant neoplasm that affects the male reproductive system. Representative examples include benign prostate phyllodes tumor, benign testicular Sertoli cell tumor, prostatic intraepithelial neoplasia, prostate carcinoma, testicular seminoma, and testicular embryonal carcinoma.
A blue, aniline-derived dye with antifungal and antimitotic properties. Gentian violet (GV) dissociates into positive (GV+) and negative ions (Cl-) that penetrate both gram-positive and gram-negative bacterial cells. The GV+ ions interact with negatively charged components of the bacterial cell wall including lipopolysaccharide, peptidoglycan and DNA. This agent is also a mutagen and mitotic poison. GV elicits a photodynamic action mediated by a free-radical mechanism. Furthermore, this agent dissipates the action potential on prokaryotic or eukaryotic membranes by inducing permeability, thereby leading to respiratory inhibition and subsequent cell death.
Germine derivatives acetylated on any one or more of the hydroxy groups. These compounds are present in many polyester alkaloids which occur in Veratrum and Zygadenus species. They are used as antihypertensive agents, and in some cases, exhibit curare-like activity.
A disorder of cognition characterized by the tetrad of finger agnosia, dysgraphia, DYSCALCULIA, and right-left disorientation. The syndrome may be developmental or acquired. Acquired Gerstmann syndrome is associated with lesions in the dominant (usually left) PARIETAL LOBE which involve the angular gyrus or subjacent white matter. (From Adams et al., Principles of Neurology, 6th ed, p457)
Genetic prion diseases generally manifest with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. Familial Creutzfeldt-Jakob disease (fCJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, and fatal familial insomnia (FFI) represent the core phenotypes of genetic prion disease. Note: A fourth clinical phenotype, known as Huntington disease like-1 (HDL-1), has been proposed, but this is based on a single report, and the underlying pathologic features would categorize it as GSS. Although it is clear that these four subtypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset ranges from the third to ninth decade of life. The course ranges from a few months to several years (typically 5-7 years; in rare instances, >10 years).
A long-acting potent progestogen structurally related to PROGESTERONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1185)
A non-estrogenic contraceptive which is a weak progestin with strong anti-progesterone properties. It is effective if used once a week orally or can also be used in intravaginal devices.
A benign, intermediate, or malignant neoplasm characterized by the presence of neoplastic giant cells.
A disorder characterized by lymphoid hyperplasia in the lymph nodes. There are two histologic variants recognized: the hyaline-vascular type and the plasma cell type. In the hyaline vascular type there are hyalinized vessels present in the lymphoid follicles. In the plasma cell type there is pronounced plasma cell proliferation. Clinically, the disease may be localized; manifested with localized lymphadenopathy, or multicentric; manifested with generalized lymphadenopathy, fever, organomegaly, and sometimes POEMS syndrome. In contrast to patients with localized disease who are usually cured following resection of the lesion, patients with the multicentric form of the disease may follow a progressive clinical course, complicated by infection, Kaposi sarcoma or lymphoma.
An infection of the SMALL INTESTINE caused by the flagellated protozoan GIARDIA. It is spread via contaminated food and water and by direct person-to-person contact.
A clinical finding indicating abnormal and excessive body growth and height resulting from the overproduction of human growth hormone.
The hereditary hyperbilirubinemias (Wolkoff et al., 1983) include (1) those resulting in predominantly unconjugated hyperbilirubinemia: Gilbert or Arias syndrome, Crigler-Najjar syndrome type I (218800), and Crigler-Najjar syndrome type II (606785); and (2) those resulting in predominantly conjugated hyperbilirubinemia: Dubin-Johnson syndrome (237500), Rotor syndrome (237450), and several forms of intrahepatic cholestasis (147480, 211600, 214950, 243300). Detailed studies show that patients with Gilbert syndrome have reduced activity of bilirubin glucuronosyltransferase (Bosma et al., 1995, Koiwai et al., 1995). Genetic Heterogeneity of Hyperbilirubinemia See also Crigler-Najjar syndrome type I (HBLRCN1; 218800), Crigler-Najjar syndrome type II (HBLRCN2; 606785), and transient familial neonatal hyperbilirubinemia (HBLRTFN; 237900), all caused by mutation in the UGT1A1 gene (191740) on chromosome 2q37; Dubin-Johnson syndrome (DJS, HBLRDJ; 237500), caused by mutation in the ABCC2 gene (601107) on chromosome 10q24; and Rotor syndrome (HBLRR; 237450), caused by digenic mutation in the SLCO1B1 (604843) and SLCOB3 (605495) genes, both on chromosome 12p.
Non-inflammatory enlargement of the gingivae produced by factors other than local irritation. It is characteristically due to an increase in the number of cells. (From Jablonski's Dictionary of Dentistry, 1992, p400)
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
A benign or malignant neoplasm that affects the upper or lower gingiva.
A loss of gum tissue resulting in an exposure of the roots of the teeth.
A disorder involving inflammation of the gums; may affect surrounding and supporting structures of the teeth.
A bacterial infectious process affecting the gums. It is characterized by the development of necrotic, ulcerated, and painful lesions with creation of pseudomembranes extending along the gingival margins.
A condition resulting from infection by Burkholderia mallei, which mainly affects horses.
An anthranilic acid derivative with analgesic properties used for the relief of all types of pain.
(1 beta,2 alpha,11 beta,12 alpha,15 beta(S))-11,20-Epoxy-1,2,11,12-tetrahydroxy-15-(2-hydroxy-2-methyl-1-oxobutoxy)picras-3-en-16-one. A quassinoid (Simaroubolide) from Simaruba glauca, a tropical shrub. It has been used as an antiamebic agent and is found to be cytotoxic. It may be of use in cancer chemotherapy.
Glaucoma is a group of eye disorders in which the optic nerves connecting the eyes and the brain are progressively damaged. This damage can lead to reduction in side (peripheral) vision and eventual blindness. Other signs and symptoms may include bulging eyes, excessive tearing, and abnormal sensitivity to light (photophobia). The term ""early-onset glaucoma"" may be used when the disorder appears before the age of 40.In most people with glaucoma, the damage to the optic nerves is caused by increased pressure within the eyes (intraocular pressure). Intraocular pressure depends on a balance between fluid entering and leaving the eyes.Usually glaucoma develops in older adults, in whom the risk of developing the disorder may be affected by a variety of medical conditions including high blood pressure (hypertension) and diabetes mellitus, as well as family history. The risk of early-onset glaucoma depends mainly on heredity.Structural abnormalities that impede fluid drainage in the eye may be present at birth and usually become apparent during the first year of life. Such abnormalities may be part of a genetic disorder that affects many body systems, called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma.Other individuals experience early onset of primary open-angle glaucoma, the most common adult form of glaucoma. If primary open-angle glaucoma develops during childhood or early adulthood, it is called juvenile open-angle glaucoma.
A form of glaucoma in which the intraocular pressure increases because the angle of the anterior chamber is blocked and the aqueous humor cannot drain from the anterior chamber.
A type of glaucoma with optic nerve damage in an eye that has evidence of angle closure and in which there is no evidence of a secondary cause.
A form of secondary glaucoma which develops as a consequence of another ocular disease and is attributed to the forming of new vessels in the angle of the anterior chamber.
A type of glaucoma defined by an open, normal appearing anterior chamber angle and raised intraocular pressure, [HPO:probinson, pmid:11815354]
A sulfonamide urea derivative with antihyperglycemic activity that can potentially be used to decrease cerebral edema. Upon administration, glyburide binds to and blocks the sulfonylurea receptor type 1 (SUR1) subunit of the ATP-sensitive inwardly-rectifying potassium (K(ATP)) channels on the membranes of pancreatic beta cells. This prevents the inward current flow of positively charged potassium (K+) ions into the cell, and induces a calcium ion (Ca2+) influx through voltage-sensitive calcium channels, which triggers exocytosis of insulin-containing granules. In addition, glyburide also inhibits the SUR1-regulated nonselective cation (NC) Ca-ATP channel, melastatin 4 (transient receptor potential cation channel subfamily M member 4; (TRPM4)), thereby preventing capillary failure and brain swelling. SUR1-TRPM4 channels are formed by co-assembly of SUR1 with TRPM4 in neurons, astrocytes, and capillary endothelium during cerebral ischemia. Upon ischemia-induced ATP depletion, channels open which results in sodium influx, cytotoxic edema formation, capillary fragmentation and necrotic cell death. SUR1-TRPM4 is not expressed in normal, uninjured tissues.
A short-acting, relatively high-potency, second-generation sulfonylurea compound with hypoglycemic activity. Gliclazide also increases peripheral insulin sensitivity. This agent is metabolized by CYP2C9.
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.
A benign or malignant brain and spinal cord tumor that arises from glial cells (astrocytes, oligodendrocytes, ependymal cells). Tumors that arise from astrocytes are called astrocytic tumors or astrocytomas. Tumors that arise from oligodendrocytes are called oligodendroglial tumors. Tumors that arise from ependymal cells are called ependymomas.
Gliosis is the focal proliferation of glial cells in the central nervous system.
A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent.
A short-acting, second-generation sulfonylurea with hypoglycemic activity. Glipizide is rapidly absorbed, has a very quick onset of action and a short half-life. This agent is extensively metabolized in the liver and the metabolites as well as the unchanged form are excreted in the urine.
Persistent or intermittent non-painful sensation of a lump or foreign body in the throat occurring between meals in the absence of dysphagia, odynophagia, evidence of gastroesophageal acid reflux, or histopathogically based esophageal motility disorders.
A rare benign or malignant mesenchymal neoplasm arising from cells that resemble the modified smooth muscle cells of the glomus body. The majority of glomus tumors occur in the distal extremities.
A renal disorder characterized by damage in the glomeruli. It may be acute or chronic, focal or diffuse, and it may lead to renal failure. Causes include autoimmune disorders, infections, diabetes, and malignancies.
End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide, affecting up to 1.3% of the population. Kidneys of patients with IgA nephropathy show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium. Typical clinical features include onset before age 40 with hematuria and proteinuria, and episodes of gross hematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence (Julian et al., 1985; D'Amico, 1987) and familial clustering (Scolari et al., 1999), along with subclinical renal abnormalities among relatives of cases, suggest a genetic component (Gharavi et al., 2000). Genetic Heterogeneity of IgA Nephropathy A locus for familial IgA nephropathy, called IGAN1, on chromosome 6q22-q23, was described by Gharavi et al. (2000). Another locus, IGAN2 (613944), was identified by Paterson et al. (2007) on chromosome 2q36. IGAN3 (616818) is caused by mutation in the SPRY2 gene (602466) on chromosome 13q31. Polymorphisms in the ACE (106180) and AGT (106150) genes have been associated with progression to chronic renal failure in patients with IgA nephropathy.
A type of glomerulonephritis characterized by diffuse mesangial cell proliferation and the thickening of capillary walls due to subendothelial extension of the mesangium. The term membranoproliferative glomerulonephritis is often employed to denote a general pattern of glomerular injury seen in a variety of disease processes that share a common pathogenetic mechanism, rather than to describe a single disease entity
A slowly progressive inflammation of the glomeruli characterized by immune complex deposits at the glomerular basement membrane, resulting in a thickened membrane, and nephrotic syndrome.
A clinicopathological syndrome or diagnostic term for a type of glomerular injury that has multiple causes, primary or secondary. Clinical features include PROTEINURIA, reduced GLOMERULAR FILTRATION RATE, and EDEMA. Kidney biopsy initially indicates focal segmental glomerular consolidation (hyalinosis) or scarring which can progress to globally sclerotic glomeruli leading to eventual KIDNEY FAILURE.
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia in the base of the skull and middle ear.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the tongue.
A benign condition characterized by the development of irregular patches in the surface of the tongue resulting in a map-like appearance. The patches migrate from day to day and usually resolve without treatment.
A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)
A usually malignant, glucagon-producing neuroendocrine tumor arising from the pancreatic alpha cells. It may be associated with necrolytic erythema migrans, diarrhea, diabetes, glossitis, weight loss, malabsorption, and anemia. Almost 25% of patients experience thromboembolic complications, and 50% have liver metastases at the time of diagnosis.
Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages.
The biosynthesis of new glucose as opposed to that generated by the metabolism of glycogen. Gluconeogenesis occurs mainly in the liver or kidneys, and involves the biosynthesis of glucose from 3-carbon or 4-carbon non-carbohydrate precursors such as amino acids or fats.
amino sugar derivative of glucose, substituted at the 2 position, occurring in glycosaminoglycans and a variety of complex polysaccharides such as blood group substances.
An amino sugar (2-amino, 2-deoxyglucose) in cell membranes, Glucosamine Sulfate is believed to play a role in cartilage formation and repair. Long-term glucosamine sulfate treatment retards progression of knee osteoarthritis; the mechanism appears to involve glucosamine's role as an essential substrate for glycosaminoglycans and hyaluronic acid, needed for formation of the joint proteoglycan structural matrix. (NCI04)
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
The monohydrate form of D-glucose, a natural monosaccharide and carbohydrate. Dextrose serves to replenish lost nutrients and electrolytes. The agent provides metabolic energy and is the primary ingredient in oral rehydration salts (ORS) and is used in intravenous (IV) fluids to provide nutrients to patients under intensive care who are unable to receive them by the oral route. Solutions containing dextrose restore blood glucose levels, provide calories, may aid in minimizing liver glycogen depletion and exerts a protein-sparing action. Dextrose also plays a role in the production of proteins and in lipid metabolism.
Solution that is usually 10 percent glucose but may be higher. An isotonic solution of glucose is 5 percent.
A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.
A hypnotic and sedative. Its use has been largely superseded by other drugs.
A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, or sweetening agent.
A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.
A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.
A bile salt formed in the liver from chenodeoxycholate and glycine, usually as the sodium salt. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is a cholagogue and choleretic.
The glycine conjugate of CHOLIC ACID. It acts as a detergent to solubilize fats for absorption and is itself absorbed.
A bile salt formed in the liver by conjugation of deoxycholate with glycine, usually as the sodium salt. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and choleretic.
A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement.
Glycogen storage disease type I (GSDI) is characterized by accumulation of glycogen and fat in the liver and kidneys, resulting in hepatomegaly and renomegaly. The two subtypes (GSDIa and GSDIb) are clinically indistinguishable. Some untreated neonates present with severe hypoglycemia; more commonly, however, untreated infants present at age three to four months with hepatomegaly, lactic acidosis, hyperuricemia, hyperlipidemia, hypertriglyceridemia, and/or hypoglycemic seizures. Affected children typically have doll-like faces with fat cheeks, relatively thin extremities, short stature, and protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function can lead to a bleeding tendency with frequent epistaxis. Untreated GSDIb is associated with impaired neutrophil and monocyte function as well as chronic neutropenia after the first few years of life, all of which result in recurrent bacterial infections and oral and intestinal mucosal ulcers. Long-term complications of untreated GSDI include growth retardation resulting in short stature, osteoporosis, delayed puberty, gout, renal disease, pulmonary hypertension, hepatic adenomas with potential for malignant transformation, polycystic ovaries, pancreatitis, and changes in brain function. Normal growth and puberty is expected in treated children. Most affected individuals live into adulthood.
Pompe disease is classified by age of onset, organ involvement, severity, and rate of progression. Infantile-onset Pompe disease (IOPD; individuals with onset before age 12 months with cardiomyopathy) may be apparent in utero but more typically onset is at the median age of four months with hypotonia, generalized muscle weakness, feeding difficulties, failure to thrive, respiratory distress, and hypertrophic cardiomyopathy. Without treatment by enzyme replacement therapy (ERT), IOPD commonly results in death by age two years from progressive left ventricular outflow obstruction and respiratory insufficiency. Late-onset Pompe disease (LOPD; including: (a) individuals with onset before age 12 months without cardiomyopathy; and (b) all individuals with onset after age 12 months) is characterized by proximal muscle weakness and respiratory insufficiency; clinically significant cardiac involvement is uncommon.
Glycogen storage disease type III (GSD III) is characterized by variable liver, cardiac muscle, and skeletal muscle involvement. GSD IIIa is the most common subtype, present in about 85% of affected individuals; it manifests with liver and muscle involvement. GSD IIIb, with liver involvement only, comprises about 15% of all GSD III. In infancy and early childhood, liver involvement presents as ketotic hypoglycemia, hepatomegaly, hyperlipidemia, and elevated hepatic transaminases. In adolescence and adulthood, liver disease becomes less prominent. Hypertrophic cardiomyopathy develops in the majority of those with GSD IIIa, usually during childhood. Its clinical significance ranges from asymptomatic in the majority to severe cardiac dysfunction, congestive heart failure, and (rarely) sudden death. Skeletal myopathy manifesting as weakness is not usually evident in childhood, but slowly progresses, typically becoming prominent in the third to fourth decade.
The clinical manifestations of glycogen storage disease type IV (GSD IV) discussed in this entry span a continuum of different subtypes with variable ages of onset, severity, and clinical features. Clinical findings vary extensively both within and between families. The fatal perinatal neuromuscular subtype presents in utero with fetal akinesia deformation sequence (FADS) with decreased fetal movements, polyhydramnios, and fetal hydrops. Death usually occurs in the neonatal period. The congenital neuromuscular subtype presents in the newborn period with profound hypotonia, respiratory distress, and dilated cardiomyopathy. Death usually occurs in early infancy. Infants with the classic (progressive) hepatic subtype may appear normal at birth, but rapidly develop failure to thrive; hepatomegaly, liver dysfunction, and progressive liver cirrhosis; hypotonia; and cardiomyopathy. Without liver transplantation, death from liver failure usually occurs by age five years. Children with the non-progressive hepatic subtype tend to present with hepatomegaly, liver dysfunction, myopathy, and hypotonia; however, they are likely to survive without progression of the liver disease and may not show cardiac, skeletal muscle, or neurologic involvement. The childhood neuromuscular subtype is rare and the course is variable, ranging from onset in the second decade with a mild disease course to a more severe, progressive course resulting in death in the third decade.
Glycogen storage disease type V (GSDV, McArdle disease) is a metabolic myopathy characterized by exercise intolerance manifested by rapid fatigue, myalgia, and cramps in exercising muscles. Symptoms usually are precipitated by isometric exercise or sustained aerobic exercise. Most individuals improve their exercise tolerance by exploiting the ""second wind"" phenomenon with relief of myalgia and fatigue after a few minutes of rest. Age of onset is frequently in the first decade of life but can vary. Fixed muscle weakness occurs in approximately 25% of affected individuals, is more likely to involve proximal muscles, and is more common in individuals of advanced age. Approximately 50% of affected individuals have recurrent episodes of myoglobinuria that could eventually result in acute renal failure, although reported cases are rare.
Glycogen storage disease type VI (GSD VI), a disorder of glycogenolysis caused by deficiency of hepatic glycogen phosphorylase, is characterized in the untreated child by hepatomegaly, growth retardation, ketotic hypoglycemia after an overnight fast, and mild hypoglycemia after prolonged fasting (e.g., during an illness). It is usually a relatively mild disorder that presents in infancy and childhood; however, severe and recurrent hypoglycemia, severe hepatomegaly, and post-prandial lactic acidosis have been described. The risk of hepatic adenoma formation in late childhood and adulthood is theoretically increased. Clinical and biochemical abnormalities may resolve with age; most adults are asymptomatic. Hypoglycemia can occur during pregnancy.
Glycogen storage disease VII is an autosomal recessive metabolic disorder characterized clinically by exercise intolerance, muscle cramping, exertional myopathy, and compensated hemolysis. Myoglobinuria may also occur. The deficiency of the muscle isoform of PFK results in a total and partial loss of muscle and red cell PFK activity, respectively. Raben and Sherman (1995) noted that not all patients with GSD VII seek medical care because in some cases it is a relatively mild disorder.
An x-linked recessive hepatic glycogen storage disease resulting from lack of expression of phosphorylase-b-kinase activity. Symptoms are relatively mild; hepatomegaly, increased liver glycogen, and decreased leukocyte phosphorylase are present. Liver shrinkage occurs in response to glucagon.
A series of anaerobic chemical reactions that cells utilize to produce energy. Glycolysis is a biochemical pathway in which glucose is catabolized into lactate or pyruvate via enzymatic reactions to generate ATP.
The alpha chain of pituitary glycoprotein hormones (THYROTROPIN; FOLLICLE STIMULATING HORMONE; LUTEINIZING HORMONE) and the placental CHORIONIC GONADOTROPIN. Within a species, the alpha subunits of these four hormones are identical; the distinct functional characteristics of these glycoprotein hormones are determined by the unique beta subunits. Both subunits, the non-covalently bound heterodimers, are required for full biologic activity.
A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics.
Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine (see ACETYLGLUCOSAMINE) or N-acetylgalactosamine (see ACETYLGALACTOSAMINE).
Lipids containing at least one monosaccharide residue and either a sphingoid or a ceramide (CERAMIDES). They are subdivided into NEUTRAL GLYCOSPHINGOLIPIDS comprising monoglycosyl- and oligoglycosylsphingoids and monoglycosyl- and oligoglycosylceramides; and ACIDIC GLYCOSPHINGOLIPIDS which comprises sialosylglycosylsphingolipids (GANGLIOSIDES); SULFOGLYCOSPHINGOLIPIDS (formerly known as sulfatides), glycuronoglycosphingolipids, and phospho- and phosphonoglycosphingolipids. (From IUPAC's webpage)
An increased concentration of glucose in the urine.
Patients with familial renal glucosuria have decreased renal tubular resorption of glucose form the urine in the absence of hyperglycemia and any other signs of tubular dysfunction. Glucosuria in these patients can range from less than 1 to over 150 g/1.73 m(2) per day (Santer and Calado, 2010).
The simplest of all peptides. It functions as a gamma-glutamyl acceptor.
A pentacyclic triterpenoid aglycone metabolite of glycyrrhizin, which is a product of the plant Glycyrrhiza glabra (licorice), with potential expectorant, and gastrokinetic activities. After administration, enoxolone inhibits the metabolism of prostaglandins by both 15-hydroxyprostaglandin dehydrogenase [NAD(+)] and prostaglandin reductase 2. Therefore, this agent potentiates the activity of prostaglandin E2 and F2alpha, which inhibits gastric secretion while stimulating pancreatic secretion and the secretion of intestinal and respiratory mucus, leading to increased intestinal motility and antitussive effects. Additionally, this agent inhibits 11 beta-hydroxysteroid dehydrogenase and other enzymes involved in the conversion of cortisol to cortisone in the kidneys.
A 2-carbon aldehyde with carbonyl groups on both carbons.
An infection that is caused by nematodes of the genus Gnathostoma, which is commonly found in Southeast Asia, and which is transmitted via the consumption of contaminated raw/undercooked birds, eels, fish, frogs, or reptiles. The pattern of symptoms is species-dependent, and extraintestinal manifestations are due to larval migration (e.g., pulmonary infiltrates, eosinophilic meningitis, or painful, pruritic subcutaneous swellings, and peripheral blood eosinophilia).
Diseases of the domestic or wild goat of the genus Capra.
DICER1-related disorders are a familial tumor susceptibility syndrome that confers increased risk most commonly for pleuropulmonary blastoma (PPB); ovarian sex cord-stromal tumors (Sertoli-Leydig cell tumor, juvenile granulosa cell tumor, and gynandroblastoma); cystic nephroma; and thyroid gland neoplasia (multinodular goiter, adenomas, or differentiated thyroid cancer). Less commonly observed tumors are ciliary body medulloepithelioma; botryoid-type embryonal rhabdomyosarcoma of the cervix or other sites; nasal chondromesenchymal hamartoma; renal sarcoma; pituitary blastoma; and pineoblastoma. Novel phenotypes continue to be discovered. The majority of tumors in families with a DICER1 germline pathogenic variant occur in individuals younger than age 40 years. PPB, a neoplasm that arises during lung development or shortly after birth, typically presents in infants and children younger than age six years. Age of onset of ovarian sex cord-stromal tumors is not well defined. CN presents in children younger than age four years.
An enlarged THYROID GLAND containing multiple nodules (THYROID NODULE), usually resulting from recurrent thyroid HYPERPLASIA and involution over many years to produce the irregular enlargement. Multinodular goiters may be nontoxic or may induce THYROTOXICOSIS.
An enlarged THYROID GLAND with at least 50% of the gland situated behind the STERNUM. It is an unusual presentation of an intrathoracic goiter. Substernal goiters frequently cause compression on the TRACHEA leading to deviation, narrowing, and respiratory symptoms.
A yellow metallic element with the atomic symbol Au, atomic number 79, and atomic weight 197. It is used in jewelry, goldplating of other metals, as currency, and in dental restoration. Many of its clinical applications, such as ANTIRHEUMATIC AGENTS, are in the form of its salts.
A suspension of radioactive gold particles emitting negative beta particles and gamma irradiation. It was formerly used for liver scans and irradiation treatment of some metastatic malignancies.
A thioglucose derivative used as an antirheumatic and experimentally to produce obesity in animals.
A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.
HYPERTENSION due to renal ISCHEMIA. In 1934, Harry Goldblatt described that hypertension can be produced experimentally by using a clamp to obstruct blood flow to one kidney, the Goldblatt phenomenon.
A non-neoplastic or neoplastic disorder that affects the testis or the ovary.
A congenital disorder characterized by the presence of extremely hypoplastic gonads preventing the development of secondary sex characteristics.
Defects in the SEX DETERMINATION PROCESS in 46, XY individuals that result in abnormal gonadal development and deficiencies in TESTOSTERONE and subsequently ANTIMULLERIAN HORMONE or other factors required for normal male sex development. This leads to the development of female phenotypes (male to female sex reversal), normal to tall stature, and bilateral streak or dysgenic gonads which are susceptible to GONADAL TISSUE NEOPLASMS. An XY gonadal dysgenesis is associated with structural abnormalities on the Y CHROMOSOME, a mutation in the GENE, SRY, or a mutation in other autosomal genes that are involved in sex determination.
A congenital condition characterized by asymmetrical gonadal development in an individual with mosaic karyotype 45,X/46,XY. 45,X/46,XY mosaic is the most common form of mixed gonadal dysgenesis.
Heterodimeric glycoprotein Gonadotropin consists of alpha (common)/beta (unique) protein subunits. The alpha subunit is present in other heterodimeric glycoprotein hormones. The beta subunit confers biological specificity and stimulates ovarian synthesis of steroids (progesterone) to maintain pregnancy.
A gonadotropic glycoprotein hormone produced primarily by the PLACENTA. Similar to the pituitary LUTEINIZING HORMONE in structure and function, chorionic gonadotropin is involved in maintaining the CORPUS LUTEUM during pregnancy. CG consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is virtually identical to the alpha subunits of the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN).
Gonadotropins secreted by the pituitary or the placenta in horses. This term generally refers to the gonadotropins found in the pregnant mare serum, a rich source of equine CHORIONIC GONADOTROPIN; LUTEINIZING HORMONE; and FOLLICLE STIMULATING HORMONE. Unlike that in humans, the equine LUTEINIZING HORMONE, BETA SUBUNIT is identical to the equine choronic gonadotropin, beta. Equine gonadotropins prepared from pregnant mare serum are used in reproductive studies.
Hormones secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR) that stimulate gonadal functions in both males and females. They include FOLLICLE STIMULATING HORMONE that stimulates germ cell maturation (OOGENESIS; SPERMATOGENESIS), and LUTEINIZING HORMONE that stimulates the production of sex steroids (ESTROGENS; PROGESTERONE; ANDROGENS).
A gonococcal infection of the lower urinary tract that is rapid in onset.
Inflammation of the urethra secondary to infection with Neisseria gonorrhoeae; this infection is spread through sexual contact.
A common sexually transmitted bacterial infection caused by Neisseria gonorrhoeae. It is transmitted through vaginal, oral, or anal intercourse. Infected individuals may be asymptomatic. Symptoms in males include burning sensation during urination, discharge from the penis, and painful swelling of the testes. Symptoms in females include painful urination, vaginal discharge, and vaginal bleeding between periods. If untreated, the infection may lead to pelvic inflammatory disease.
A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer.
Gout is a type of arthritis, which is a group of related disorders caused by episodes of abnormal inflammation in the joints. People with gout have high levels of a substance called urate in the blood (hyperuricemia). Gout develops when hyperuricemia leads to the formation of urate crystals in joints, triggering an inflammatory response from the immune system.In people with gout, the first episode of inflammation (called a flare) usually affects the big toe or other joints in the foot or ankle. If urate levels remain high, flares can recur, affecting additional joints throughout the body. The time between flares varies among affected individuals; however, most people who experience multiple flares have their second one within a year of their first.Flares usually begin at night and can last several days. It is unclear what causes a flare to stop; the body likely turns off the inflammation response after a certain period of time. During a flare, individuals can experience throbbing or burning pain, swelling, warmth, redness, and difficulty moving the affected joint. Fevers may occur, after which the skin over the affected joint can begin to peel. Without treatment, people with gout can experience frequent flares and joint pain and damage, which can limit mobility and decrease quality of life.In about 15 percent of people with gout, urate accumulates in the kidneys and forms kidney stones. As the condition worsens, urate crystals can also be deposited under the skin or in other soft tissue, forming a nodule called a tophus (plural: tophi). These tophi often form in the hands, elbows, or feet. Tophi do not typically cause pain, but they can become inflamed, infected, or ooze fluid. Depending on their location, tophi can interfere with movements such as walking or gripping objects.Many people with gout also have other health conditions. Most affected individuals have high blood pressure (hypertension), chronic kidney disease, or obesity. Some also have diabetes, heart disease, or a history of stroke. It is unclear whether gout is the cause of a person's increased risk for these conditions, or whether the conditions cause the development of gout, or whether both of these situations occur to influence disease.
Agents that increase uric acid excretion by the kidney (URICOSURIC AGENTS), decrease uric acid production (antihyperuricemics), or alleviate the pain and inflammation of acute attacks of gout.
Inflammation of PETROUS BONE secondary to chronic OTITIS MEDIA. Its symptoms include fever, occipital headache, ear and retroorbital pain, and facial paralysis.
Obstruction of flow in biological or prosthetic vascular grafts.
A reaction, which may be fatal, in an immunocompromised subject (host) who has received an antigenically incompatible tissue transplant (graft) from an immunocompetent donor. The reaction is secondary to the activation of the transplanted cells against those host tissues that express an antigen not expressed by the donor, and is seen most commonly following bone marrow transplantation; acute disease is seen after 5-40 days, and chronic disease occurs weeks to months after transplantation.
An immunological attack mounted by a graft against the host because of tissue incompatibility when immunologically competent cells are transplanted to an immunologically incompetent host; the resulting clinical picture is that of GRAFT VS HOST DISEASE.
A stromal corneal dystrophy that is caused by mutation(s) in the TGFBI gene.
A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents.
A condition resulting from infection by Klebsiella granulomati, which is characterized by ulcerative lesions of the genitalia.
An inflammatory lesion comprised of epithelioid histiocytes and chronic inflammation that is caused by the presence of extraneous material.
A non-neoplastic inflammatory lesion, usually of the jaw or gingiva, containing large, multinucleated cells. It includes reparative giant cell granuloma. Peripheral giant cell granuloma refers to the gingiva (giant cell epulis); central refers to the jaw.
A tumor-like nodule or mass of inflammatory granulation tissue projecting into the lumen of the LARYNX.
An aggressive, progressive, and destructive lesion affecting the nasal cavities, paranasal sinuses, and the palate. The vast majority of cases are malignant lymphoproliferations affecting the midline of the face in patients with nasal type extranodal NK/T-cell lymphoma.
A slow-growing benign pseudotumor in which plasma cells greatly outnumber the inflammatory cells.
Granulomatous disorders affecting one or more sites in the respiratory tract.
Inflammation of the arteries that is characterized by the presence of granulomas.
A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the CYBB gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by CYBA, NCF1, NCF2, or NCF4 gene mutations, the condition is inherited in an autosomal recessive pattern.
An infectious or non-infectious inflammatory process that affects the prostate gland. Infectious causative agents include bacteria, parasites, fungi, and viruses. It is characterized by the formation of granulomas in the prostatic tissue.
A neoplasm composed entirely of GRANULOSA CELLS, occurring mostly in the OVARY. In the adult form, it may contain some THECA CELLS. This tumor often produces ESTRADIOL and INHIBIN. The excess estrogen exposure can lead to other malignancies in women and PRECOCIOUS PUBERTY in girls. In rare cases, granulosa cell tumors have been identified in the TESTES.
An autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones (a serious metabolic imbalance known as hyperthyroidism and thyrotoxicosis). This is caused by autoantibodies to the TSH-receptor (TSHR-Ab) that activate that TSH-receptor (TSHR), thereby stimulating thyroid hormone synthesis and secretion, and thyroid growth (causing a diffusely enlarged goiter). The resulting state of hyperthyroidism can cause a dramatic constellation of neuropsychological and physical signs and symptoms, which can severely compromise the patients.
An antifungal agent derived from the mold Penicillium griseofulvum that is used to treat fungal infections of the skin and nails. Griseofulvin binds to tubulin, disrupting microtubule function and inhibiting mitosis.
Deviations from the average values for a specific age and sex in any or all of the following: height, weight, skeletal proportions, osseous development, or maturation of features. Included here are both acceleration and retardation of growth.
Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth (= PLANT GROWTH REGULATORS).
An agent thought to have disinfectant properties and used as an expectorant. (From Martindale, The Extra Pharmacopoeia, 30th ed, p747)
A glyceryl guaiacolate with expectorant effects. Guaifenesin increases respiratory tract mucus secretions, acts as an irritant to gastric vagal receptors and recruits efferent parasympathetic reflexes that cause glandular exocytosis. This agent reduces the viscosity of mucus secretion by reducing adhesiveness and surface tension as well as increasing hydration of mucus. Guaifenesin promotes the efficiency of the mucociliary mechanism important in removing accumulated secretions from the upper and lower airway.
An alpha-2 selective adrenergic agonist used as an antihypertensive agent.
A cytostatic triazole derivative antimetabolite. Guanazole scavenges tyrosine free radicals, thereby inhibiting mammalian ribonucleotide reductase activity and DNA synthesis. (NCI04)
An antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues.
A purine nucleoside formed from a beta-N9-glycosidic bond between guanine and a ribose ring and is essential for metabolism.
May protect against hypoxic damage; proposed for treatment of shock due to trauma or blood loss; also stimulates paretic gastrointestinal system.
A rapidly progressive autoimmune disorder of the peripheral nervous system characterized by limb paresthesias, areflexia, and generalized muscle weakness or paralysis that often begins in the legs and spreads to the arms, torso, and face.
Powdered exudate from various Acacia species, especially A. senegal (Leguminosae). It forms mucilage or syrup in water. Gum arabic is used as a suspending agent, excipient, and emulsifier in foods and pharmaceuticals.
A sex cord-gonadal stromal tumor, composed of cells of both the OVARY and the TESTIS. It produces both male and female GONADAL STEROID HORMONES.
A congenital or acquired occlusion of an opening in any part of the female genital tract.
Abnormal development of large mammary glands in males resulting in breast enlargement.
A rare autosomal recessive inherited disorder caused by mutations in the OAT gene. It is characterized by progressive atrophy of the retina and choroid, leading to loss of vision and blindness.
Infection with nematodes of the genus HAEMONCHUS, characterized by digestive abnormalities and anemia similar to that from hookworm infestation.
An infection that is caused by the organism Hemophilus.
A non-neoplastic or neoplastic disorder involving the hair. Representative examples include folliculitis, alopecia, tricholemmoma, and pilomatrical carcinoma.
A usually benign congenital skin growth that is often pigmented and sometimes develop coarse surface hair. There is a lifetime risk of transformation to malignant melanoma which varies depending on the size of the lesion.
A glucocorticoid used topically in the treatment of DERMATITIS; ECZEMA; or PSORIASIS. It may cause skin irritation.
An offensive, foul breath odor resulting from a variety of causes such as poor oral hygiene, dental or oral infections, or the ingestion of certain foods.
Hallermann-Streiff syndrome is characterized by a typical skull shape (brachycephaly with frontal bossing), hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, skin atrophy, dental anomalies, and proportionate short stature (Hallermann, 1948; Streiff, 1950; Francois, 1958). Mental retardation is present in a minority of cases (Gorlin et al., 1990).
Pantothenate kinase-associated neurodegeneration (PKAN) is a type of neurodegeneration with brain iron accumulation (NBIA). The phenotypic spectrum of PKAN includes classic PKAN and atypical PKAN. Classic PKAN is characterized by early childhood onset of progressive dystonia, dysarthria, rigidity, and choreoathetosis. Pigmentary retinal degeneration is common. Atypical PKAN is characterized by later onset (age >10 years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease.
A false sensory perception in the absence of an external stimulus, as distinct from an illusion which is a misperception of an external stimulus.
A drug dependence for a hallucinogenic substance.
Any naturally-derived or synthetic substance that can induce hallucinations.
A deformity characterized by lateral deviation of the great toe.
A selective peroxisome proliferator-activated receptor gamma (PPAR-gamma) modulator with antilipidemic activity. Halofenate also decreases fasting plasma glucose in type 2 diabetic patients, but not normoglycemic subjects.
A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
A nonflammable, halogenated, hydrocarbon and general inhalation anesthetic. Although the exact mechanism of action is unknown, halothane provides relatively rapid induction of anesthesia by depressing the central nervous system, thereby producing a reversible loss of consciousness and sensation. (NCI05)
A benign and excessive tumor-like growth of mature cells and normal tissues which grow in a disorganized pattern.
Cowden syndrome-1 is a hamartomatous disorder characterized by macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules, and an increased risk for the development of breast, thyroid, and endometrial carcinoma. Bannayan-Riley-Ruvalcaba syndrome (BRRS), previously thought be distinct, shared clinical characteristics with Cowden syndrome, such as hamartomatous polyps of the gastrointestinal tract, mucocutaneous lesions, and increased risk of developing neoplasms, but had the additional features of developmental delay, macrocephaly, lipomas, hemangiomas, and pigmented speckled macules of the glans penis in males. Because features of BRRS and Cowden syndrome have been found in individuals within the same family with the same PTEN mutation, Cowden syndrome-1 and BRRS are considered to be the same disorder with variable expression and age-related penetrance (summary by Marsh et al., 1999, Lachlan et al., 2007, and Blumenthal and Dennis, 2008). Approximately 80% of patients reported with Cowden syndrome and 60% with BRSS have PTEN mutations (Blumenthal and Dennis, 2008). Some patients with Cowden syndrome may have immune system defects resulting in increased susceptibility to infections (summary by Browning et al., 2015).
Alterations or deviations from normal shape or size which result in a disfigurement of the hand.
Alterations or deviations from normal shape or size which result in a disfigurement of the hand occurring at or before birth.
A clinical syndrome that is usually caused by enterovirus infection, and that is characterized by fever, anorexia, and painful sores in the mouth, distal extremities, and/or other sites, including the buttocks.
A melanin-forming tumor that arose spontaneously in a non-inbred mouse, and that is transplantable to mice of many strains but does not ordinarily metastasize. (dictionarybarn.com)
A beta-carboline alkaloid isolated from seeds of PEGANUM.
Alkaloid isolated from seeds of Peganum harmala L., Zygophyllaceae. It is identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic Parkinson disease in the 1920's.
Tetracyclic spiro-BENZAZEPINES isolated from the seeds of CEPHALOTAXUS. They are esters of the alkaloid cephalotaxine and may be effective as antineoplastic agents.
Hartnup disease is a condition caused by the body's inability to absorb certain protein building blocks (amino acids) from the diet. As a result, affected individuals are not able to use these amino acids to produce other substances, such as vitamins and proteins. Most people with Hartnup disease are able to get the vitamins and other substances they need with a well-balanced diet.People with Hartnup disease have high levels of various amino acids in their urine (aminoaciduria). For most affected individuals, this is the only sign of the condition. However, some people with Hartnup disease have episodes during which they exhibit other signs, which can include skin rashes; difficulty coordinating movements (cerebellar ataxia); and psychiatric symptoms, such as depression or psychosis. These episodes are typically temporary and are often triggered by illness, stress, nutrient-poor diet, or fever. These features tend to go away once the trigger is remedied, although the aminoaciduria remains. In affected individuals, signs and symptoms most commonly occur in childhood.
Allergic rhinitis caused by outdoor allergens.
A benign or malignant neoplasm that affects the anatomic structures of the head and neck region. Representative examples of benign neoplasms include salivary gland pleomorphic adenoma and nasal cavity papilloma. Representative examples of malignant neoplasms include oral cavity squamous cell carcinoma, laryngeal squamous cell carcinoma, and salivary gland carcinoma.
Habitual striking of one's own head against a surface such as a mattress or wall of a crib.
Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.
The ability of individuals or a population to utilize and obtain care from the health care system.
A decreased magnitude of the sensory perception of sound.
Hearing loss due to disease of the AUDITORY PATHWAYS (in the CENTRAL NERVOUS SYSTEM) which originate in the COCHLEAR NUCLEI of the PONS and then ascend bilaterally to the MIDBRAIN, the THALAMUS, and then the AUDITORY CORTEX in the TEMPORAL LOBE. Bilateral lesions of the auditory pathways are usually required to cause central hearing loss. Cortical deafness refers to loss of hearing due to bilateral auditory cortex lesions. Unilateral BRAIN STEM lesions involving the cochlear nuclei may result in unilateral hearing loss.
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Hearing loss in the absence of auditory system pathology.
A condition in which a person loses the ability to hear high frequency sounds. It is typically associated with impairment of the inner ear.
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
A localized bulging or dilatation in the muscle wall of a heart (MYOCARDIUM), usually in the LEFT VENTRICLE. Blood-filled aneurysms are dangerous because they may burst. Fibrous aneurysms interfere with the heart function through the loss of contractility. True aneurysm is bound by the vessel wall or cardiac wall. False aneurysms are HEMATOMA caused by myocardial rupture.
Impaired conduction of cardiac impulse occurring anywhere along the conduction pathway.
An anatomical defect of a gross structure of the heart.
A non-neoplastic or neoplastic disorder that affects the heart and/or the pericardium. Representative examples include endocarditis, pericarditis, atrial myxoma, cardiac myeloid sarcoma, and pericardial malignant mesothelioma.
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.
Failure of the heart to pump a sufficient amount of blood to meet the needs of the body tissues, resulting in tissue congestion and edema. Signs and symptoms include shortness of breath, pitting edema, enlarged tender liver, engorged neck veins, and pulmonary rales.
A periodic humming or blowing sound heard on auscultation of the heart that can indicate the presence of cardiac disease; murmurs are the result of vibrations caused by the turbulent flow of blood in the heart or great vessels. Murmurs are characterized according to the area of generation (mitral, aortic, tricuspid, or pulmonary) and according to the period of the cycle (systolic or diastolic).
A benign or malignant neoplasm that affects the heart and/or the pericardium. Representative examples include atrial myxoma, cardiac myeloid sarcoma, and pericardial malignant mesothelioma.
The heart rate of the FETUS. The normal range at term is between 120 and 160 beats per minute.
Disease-related laceration or tearing of tissues of the heart, including the free-wall MYOCARDIUM; HEART SEPTUM; PAPILLARY MUSCLES; CHORDAE TENDINEAE; and any of the HEART VALVES. Pathological rupture usually results from myocardial infarction (HEART RUPTURE, POST-INFARCTION).
Tearing of the heart muscle as a sequela of acute myocardial infarction.
A congenital disorder characterized by the presence of an abnormal communication between the atria or the ventricles of the heart due to defects in the cardiac septum.
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Any heart disorder characterized by a defect in valve structure or function.
Abdominal discomfort with retrosternal pain usually associated with gastroesophageal reflux..
A tick-borne septicemic disease of domestic and wild ruminants caused by EHRLICHIA RUMINANTIUM.
A group of rare disorders of immunoglobulin synthesis associated with B-cell proliferative disorders.
A clonal disorder characterized by the secretion of a truncated gamma chain. In most cases, it is associated with morphologic changes also seen in lymphoplasmacytic lymphomas, but the clinical course is typically more aggressive than in lymphoplasmacytic lymphoma.
Bony swelling of the distal interphalangeal joint (DIP) associated with the formation of osteophytes (calcific spurs) of the articular (joint) cartilage thzat are visible radiographically.
A gaseous element with atomic symbol He, atomic number 2, and atomic weight 4.00.
A parasitic infection characterized by the infestation with worms, mainly in the intestine.
Infestation of animals with parasitic worms of the helminth class. The infestation may be experimental or veterinary.
The aggregation of ERYTHROCYTES by AGGLUTININS, including antibodies, lectins, and viral proteins (HEMAGGLUTINATION, VIRAL).
A vascular proliferation characterized by the presence of prominent endothelial cells and the formation of vascular channels. Hemangioendotheliomas may display borderline or low grade characteristics.
A benign vascular lesion characterized by the formation of capillary-sized or cavernous vascular channels.
A hemangioma characterized by the presence of cavernous vascular spaces.
An antiquated term that refers to benign or malignant mesenchymal neoplasms characterized by the presence of neoplastic spindle-shaped to round cells arranged around thin-walled branching vascular spaces.
A malignant tumor arising from the endothelial cells of the blood vessels. Microscopically, it is characterized by frequently open vascular anastomosing and branching channels. The malignant cells that line the vascular channels are spindle or epithelioid and often display hyperchromatic nuclei. Angiosarcomas most frequently occur in the skin and breast. Patients with long-standing lymphedema are at increased risk of developing angiosarcoma.
Bleeding into the joints. It may arise from trauma or spontaneously in patients with hemophilia.
Agents which improve the quality of the blood, increasing the hemoglobin level and the number of erythrocytes. They are used in the treatment of anemias.
Hemorrhage into a canal or cavity of the body, such as the space covered by the serous membrane (tunica vaginalis) around the TESTIS leading to testicular hematocele or scrotal hematocele.
The passage of bright red blood from the rectum. The blood may or may not be mixed with formed stool in the form of blood, blood clots, bloody stool or diarrhea.
A blood-filled VAGINA that is obstructed.
Drugs that act on blood and blood-forming organs and those that affect the hemostatic system.
A neoplastic or non-neoplastic disorder that affects the production and proliferation of the hematopoietic cells including lymphoid cells, the synthesis of hemoglobin, and/or the mechanisms of coagulation.
A collection of blood outside the BLOOD VESSELS. Hematoma can be localized in an organ, space, or tissue.
A collection of blood between the dura mater and the brain.
The presence of blood in a fallopian tube.
A visual defect characterized by the inability to see as clearly in bright light as in dim light. The word hemeralopia literally means day blindness.
Lack of sight in half of the normal field of vision.
Hematologic diseases and diseases of the lymphatic system collectively. Hemic diseases include disorders involving the formed elements (e.g., ERYTHROCYTE AGGREGATION, INTRAVASCULAR) and chemical components (e.g., BLOOD PROTEIN DISORDERS); lymphatic diseases include disorders relating to lymph, lymph nodes, and lymphocytes.
A potent inhibitor of the high affinity uptake system for CHOLINE. It has less effect on the low affinity uptake system. Since choline is one of the components of ACETYLCHOLINE, treatment with hemicholinium can deplete acetylcholine from cholinergic terminals. Hemicholinium 3 is commonly used as a research tool in animal and in vitro experiments.
A congenital malformation characterized by the partial or total absence of the distal half of a limb.
Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen.
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
Paralysis (complete loss of muscle function) in the arm, leg, and in some cases the face on one side of the body.
A disorder of iron metabolism characterized by a triad of HEMOSIDEROSIS; LIVER CIRRHOSIS; and DIABETES MELLITUS. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)
Solutions prepared for hemodialysis. The composition of the pre-dialysis solution may be varied in order to determine the effect of solvated metabolites on anoxia, malnutrition, acid-base balance, etc. Of principal interest are the effect of the choice of buffers (e.g., acetate or carbonate), the addition of cations (Na+, K+, Ca2+), and addition of carbohydrates (glucose).
A disease characterized by compensated hemolysis with a normal hemoglobin level or a mild to moderate anemia. There may be intermittent abdominal discomfort, splenomegaly, and slight jaundice.
The persistence of substantial fetal hemoglobin production into adulthood, usually associated with hemoglobinopathies due to mutations in the alpha and/or beta chain of hemoglobin.
A hemoglobinopathy that is considered a hybrid of sickle cell disease and hemoglobin C disease. Patients present with the symptoms of sickle cell disease but the latter are less frequent and severe compared to sickle cell disease.
Detection of hemoglobin in a location it should not normally be present
A group of inherited disorders characterized by structural alterations within the hemoglobin molecule.
A laboratory test result which indicates free hemoglobin in the urine.
Hemoglobin in the urine that is due to hemolysis from an external cause.
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.
A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.
Accumulation of blood within the pericardial sac.
Accumulation of blood in the peritoneal cavity owing to internal hemorrhage.
Bleeding into the peritoneal cavity that is not associated with physical trauma.
Proliferation of HISTIOCYTES in response to viral, bacterial, fungal, or parasitic infections.
Hemophilia A is characterized by deficiency in factor VIII clotting activity that results in prolonged oozing after injuries, tooth extractions, or surgery, and delayed or recurrent bleeding prior to complete wound healing. The age of diagnosis and frequency of bleeding episodes are related to the level of factor VIII clotting activity. Individuals with severe hemophilia A are usually diagnosed during the first two years of life following bleeding from minor mouth injuries and large ""goose eggs"" from minor head bumps. Without prophylactic treatment, they may average up to two to five spontaneous bleeding episodes each month including spontaneous joint bleeds or deep-muscle hematomas, and prolonged bleeding or excessive pain and swelling from minor injuries, surgery, and tooth extractions. Individuals with moderate hemophilia A seldom have spontaneous bleeding; however, they do have prolonged or delayed oozing after relatively minor trauma and are usually diagnosed before age five to six years; the frequency of bleeding episodes varies, usually from once a month to once a year. Individuals with mild hemophilia A do not have spontaneous bleeding episodes; however, without pre- and postoperative treatment, abnormal bleeding occurs with surgery or tooth extractions; the frequency of bleeding episodes varies widely, typically from once a year to once every ten years. Individuals with mild hemophilia A are often not diagnosed until later in life. Approximately 30% of heterozygous females have clotting activity below 40% and are at risk for bleeding (even if the affected family member is mildly affected). After major trauma or invasive procedures, prolonged or excessive bleeding usually occurs, regardless of severity.
Collection of air and blood in the pleural cavity.
Coughing up (expectoration) of blood or blood-streaked sputum from the larynx, trachea, bronchi, or lungs.
Bleeding or escape of blood from a vessel.
Bleeding originating from the rectal wall and anus.
Accumulation of hemorrhagic fluid in the peritoneal cavity.
Spontaneous or near spontaneous bleeding caused by a defect in clotting mechanisms (BLOOD COAGULATION DISORDERS) or another abnormality causing a structural flaw in the blood vessels (HEMOSTATIC DISORDERS).
A condition characterized as a coagulation disturbance in newborns due to vitamin K deficiency resulting in impaired production of coagulation factors II, VII, IX, and X, and proteins C and S by the liver.
Diseases caused by American hemorrhagic fever viruses (ARENAVIRUSES, NEW WORLD).
A severe, often fatal disease in humans caused by the Crimean-Congo hemorrhagic fever virus (HEMORRHAGIC FEVER VIRUS, CRIMEAN-CONGO).
A serious condition caused by Dengue virus infection. Patients present with an acute febrile illness followed by restlessness, irritability, and bleeding. It may lead to hemorrhagic shock and death.
Haemorrhagic fever with renal syndrome (HFRS) is a rodent-borne potentially severe haemorrhagic disease caused by Old World Hantaviruses characterised by high fever, malaise, headache, myalgia, arthralgia, backache, abdominal pain, oliguria/renal failure and systemic haemorrhagic manifestations.
Infection with the Omsk hemorrhagic fever virus, a Flavivirus.
A group of viral diseases of diverse etiology but having many similar clinical characteristics; increased capillary permeability, leukopenia, and thrombocytopenia are common to all. Hemorrhagic fevers are characterized by sudden onset, fever, headache, generalized myalgia, backache, conjunctivitis, and severe prostration, followed by various hemorrhagic symptoms. Hemorrhagic fever with kidney involvement is HEMORRHAGIC FEVER WITH RENAL SYNDROME.
Accumulation of iron in internal organs.
Agents acting to arrest the flow of blood. Absorbable hemostatics arrest bleeding either by the formation of an artificial clot or by providing a mechanical matrix that facilitates clotting when applied directly to the bleeding surface. These agents function more at the capillary level and are not effective at stemming arterial or venous bleeding under any significant intravascular pressure.
A collection of blood in the pleural cavity.
A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.
Coagulant substances inhibiting the anticoagulant action of heparin.
A sulfated plasma protein with a MW of approximately 66kDa that resembles ANTITHROMBIN III. The protein is an inhibitor of thrombin in plasma and is activated by dermatan sulfate or heparin. It is a member of the serpin superfamily.
Heparin fractions with a molecular weight usually between 4000 and 6000 kD. These low-molecular-weight fractions are effective antithrombotic agents. Their administration reduces the risk of hemorrhage, they have a longer half-life, and their platelet interactions are reduced in comparison to unfractionated heparin. They also provide an effective prophylaxis against postoperative major pulmonary embolism.
Heparin derivatives. The term has also been used more loosely to include naturally occurring and synthetic highly-sulphated polysaccharides of similar structure. Heparinoid preparations have been used for a wide range of applications including as anticoagulants and anti-inflammatories and they have been claimed to have hypolipidemic properties. (From Martindale, The Extra Pharmacopoeia, 30th, p232)
A constellation of signs and symptoms characterized by changes in personality, consciousness, and reflexes, resulting from neuropsychiatric abnormalities secondary to liver failure without evidence of other brain disease.
An obstruction in the veins of the liver caused by a blood clot (thrombosis).
A disorder characterized by damage of the hepatic sinusoidal endothelial cells of the hepatic venules that leads to venular occlusion and hepatocellular necrosis. It is usually the side effect of high dose chemotherapy in preparation for stem cell transplantation. Less frequently it may be caused by ingestion of plant alkaloids. The clinical signs and symptoms include hyperbilirubinemia, hepatomegaly, and fluid retention.
Acute inflammation of the liver caused by the hepatitis A virus. It is highly contagious and usually contracted through close contact with an infected individual or their feces, contaminated food or water.
A viral infection caused by the hepatitis B virus.
Any one of the hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.
INFLAMMATION of the LIVER due to ALCOHOL ABUSE. It is characterized by NECROSIS of HEPATOCYTES, infiltration by NEUTROPHILS, and deposit of MALLORY BODIES. Depending on its severity, the inflammatory lesion may be reversible or progress to LIVER CIRRHOSIS.
INFLAMMATION of the LIVER in non-human animals.
An active inflammatory process affecting the liver for more than six months. Causes include viral infections, autoimmune disorders, drugs, and metabolic disorders.
A contagious disease caused by canine adenovirus (ADENOVIRUSES, CANINE) infecting the LIVER, the EYE, the KIDNEY, and other organs in dogs, other canids, and bears. Symptoms include FEVER; EDEMA; VOMITING; and DIARRHEA.
INFLAMMATION of the LIVER in animals due to viral infection.
INFLAMMATION of the LIVER in humans due to infection by VIRUSES. There are several significant types of human viral hepatitis with infection caused by enteric-transmission (HEPATITIS A; HEPATITIS E) or blood transfusion (HEPATITIS B; HEPATITIS C; and HEPATITIS D).
A viral infection caused by the hepatitis C virus.
Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to older than 50 years; symptoms vary among and within families. Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings, frequently present, result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body.
A syndrome characterized by progressive kidney failure in a patient with cirrhosis or fulminant liver failure.
An abnormal enlargement of both the liver and spleen.
An amino alcohol that has been used as a myocardial stimulant and vasodilator and to relieve bronchospasm. Its most common therapeutic use is in orthostatic hypotension. The mechanism of heptaminol's therapeutic actions is not well understood although it has been suggested to affect catecholamine release or calcium metabolism.
Hereditary angioedema is a disorder characterized by recurrent episodes of severe swelling (angioedema). The most common areas of the body to develop swelling are the limbs, face, intestinal tract, and airway. Minor trauma or stress may trigger an attack, but swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway. About one-third of people with this condition develop a non-itchy rash called erythema marginatum during an attack.Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty. On average, untreated individuals have an attack every 1 to 2 weeks, and most episodes last for about 3 to 4 days. The frequency and duration of attacks vary greatly among people with hereditary angioedema, even among people in the same family.There are three types of hereditary angioedema, called types I, II, and III, which can be distinguished by their underlying causes and levels of a protein called C1 inhibitor in the blood. The different types have similar signs and symptoms. Type III was originally thought to occur only in women, but families with affected males have been identified.
Diseases caused by genetic mutations that are inherited from a parent's genome.
Congenital afibrinogenemia is a bleeding disorder caused by impairment of the blood clotting process. Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, bleeding is uncontrolled in people with congenital afibrinogenemia. Newborns with this condition often experience prolonged bleeding from the umbilical cord stump after birth. Nosebleeds (epistaxis) and bleeding from the gums or tongue are common and can occur after minor trauma or in the absence of injury (spontaneous bleeding). Some affected individuals experience bleeding into the spaces between joints (hemarthrosis) or the muscles (hematoma). Rarely, bleeding in the brain or other internal organs occurs, which can be fatal. Women with congenital afibrinogenemia can have abnormally heavy menstrual bleeding (menorrhagia). Without proper treatment, women with this disorder may have difficulty carrying a pregnancy to term, resulting in repeated miscarriages.
The transmission of traits encoded in GENES from parent to offspring.
An historical term for a variety of abnormalities in sex development that lead to anomalies in the reproductive tract and/or external genitalia.
Protrusion of tissue, structure, or part of an organ through the bone, muscular tissue, or the membrane by which it is normally contained. Hernia may involve tissues such as the ABDOMINAL WALL or the respiratory DIAPHRAGM. Hernias may be internal, external, congenital, or acquired.
The protrusion of an organ, or the fascia of an organ, through the wall of the cavity that normally contains it, without mention of obstruction or necrosis of the herniated contents.
A congenital or acquired weakness or opening in the diaphragm which allows abdominal contents to protrude into the chest cavity; congenital diaphragmatic hernias are caused when the embryonic diaphragm fails to fuse.
Protrusion of abdominal cavity contents or pre-peritoneal fat through the abdominal wall between the umbilicus and the xiphoid process.
A groin hernia occurring inferior to the inguinal ligament and medial to the FEMORAL VEIN and FEMORAL ARTERY. The femoral hernia sac has a small neck but may enlarge considerably when it enters the subcutaneous tissue of the thigh. It is caused by defects in the ABDOMINAL WALL.
An abdominal hernia with an external bulge in the GROIN region. It can be classified by the location of herniation. Indirect inguinal hernias occur through the internal inguinal ring. Direct inguinal hernias occur through defects in the ABDOMINAL WALL (transversalis fascia) in Hesselbach's triangle. The former type is commonly seen in children and young adults; the latter in adults.
A protrusion of the abdominal cavity contents into the inguinal canal through the superficial inguinal ring.
A protrusion of the abdominal cavity contents into the inguinal canal through the deep and superficial inguinal rings.
A pelvic hernia through the obturator foramen, a large aperture in the hip bone normally covered by a membrane. Obturator hernia can lead to intestinal incarceration and INTESTINAL OBSTRUCTION.
The protrusion of abdominal cavity contents into the scrotal sac.
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
A hernia caused by weakness of the anterior ABDOMINAL WALL due to midline defects, previous incisions, or increased intra-abdominal pressure. Ventral hernias include UMBILICAL HERNIA, incisional, epigastric, and spigelian hernias.
Physical and psychological dependence on the drug heroin.
Acute types of coxsackievirus infections or ECHOVIRUS INFECTIONS that usually affect children during the summer and are characterized by vesiculoulcerative lesions on the MUCOUS MEMBRANES of the THROAT; DYSPHAGIA; VOMITING, and FEVER.
Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of small vesicles in clusters.
Herpes simplex infection of the genitals, most commonly caused by the herpes simplex-2 virus.
An autoimmune bullous dermatitis that develops during pregnancy, most often during the second and third trimesters.
A lesion caused by type 1 or type 2 herpes simplex virus, involving the oralfacial region.
A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.)
A superficial, epithelial Herpesvirus hominis infection of the cornea, characterized by the presence of small vesicles which may break down and coalesce to form dendritic ulcers (KERATITIS, DENDRITIC). (Dictionary of Visual Science, 3d ed)
A common dermal and neurologic disorder caused by reactivation of the varicella-zoster virus that has remained dormant within dorsal root ganglia, often for decades, after the patient's initial exposure to the virus in the form of varicella (chickenpox). It is characterized by severe neuralgic pain along the distribution of the affected nerve and crops of clustered vesicles over the area.
A form of herpes zoster infection characterized by dermatitis of the skin of the eyelid due to reactivation of latent virus associated with the ophthalmic branch of the trigeminal nerve.
Virus infection of the Gasserian ganglion and its nerve branches characterized by pain and vesicular eruptions with much swelling. Ocular involvement is usually heralded by a vesicle on the tip of the nose. This area is innervated by the nasociliary nerve.
Virus diseases caused by the HERPESVIRIDAE.
Infection of the vulva and the vagina caused by herpes simplex virus.
A flavanone glycoside found in CITRUS fruit peels.
A chlorinated bisphenol antiseptic agent with bacteriostatic activity. Hexachlorophene is used topically in soaps, creams and dermatological preparations and is active against gram-positive organisms, but much less effective against gram-negative organisms. (NCI05)
A synthetic polymer which agglutinates red blood cells. It is used as a heparin antagonist.
A hexamethyl-2,4,6-triamine derivative of 1,3,5-triazine.
A synthetic estrogen that has been used as a hormonal antineoplastic agent.
A bactericidal and fungicidal antiseptic. It is used as a 0.1% mouthwash for local infections and oral hygiene. (From Martindale, The Extra Pharmacopoeia, 30th ed, p797)
A barbiturate that is effective as a hypnotic and sedative.
A potent vasoactive agent that dilates cerebral and coronary arteries, but slightly constricts femoral arteries, without any effects on heart rate, blood pressure or cardiac output.
Stimulant of adrenergic beta 2 receptors. It is used as a bronchodilator, antiasthmatic agent, and tocolytic agent.
A substituted dihydroxybenzene used topically as an antiseptic for the treatment of minor skin infections.
A contraction of the diaphragm that repeats several times per minute. In humans, the abrupt rush of air into the lungs causes the epiglottis to close, creating a hic sound. Also known as synchronous diaphragmatic flutter (SDF), or singultus, from the Latin singult, the act of catching one's breath while sobbing. The hiccup is an involuntary action involving a reflex arc.
A benign epithelial neoplasm arising from the sweat glands. Representative examples include tubular apocrine adenoma, syringofibroadenoma, and hidradenoma.
A syndrome related to increased atmospheric pressure and characterized by tremors, nausea, dizziness, decreased motor and mental performance, and SEIZURES. This condition may occur in those who dive deeply (c. 1000 ft) usually while breathing a mixture of oxygen and helium. The condition is associated with a neuroexcitatory effect of helium.
A congenital or traumatic abnormality in which the femoral head slips out of the acetabulum.
The presence of developmental dysplasia of the hip.
A hereditary disease of the hip joints in dogs. Signs of the disease may be evident any time after 4 weeks of age.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the hip.
Von Hippel-Lindau (VHL) syndrome is characterized by hemangioblastomas of the brain, spinal cord, and retina; renal cysts and clear cell renal cell carcinoma; pheochromocytoma, pancreatic cysts, and neuroendocrine tumors; endolymphatic sac tumors; and epididymal and broad ligament cysts. Cerebellar hemangioblastomas may be associated with headache, vomiting, gait disturbances, or ataxia. Spinal hemangioblastomas and related syrinx usually present with pain. Sensory and motor loss may develop with cord compression. Retinal hemangioblastomas may be the initial manifestation of VHL syndrome and can cause vision loss. Renal cell carcinoma occurs in about 70% of individuals with VHL and is the leading cause of mortality. Pheochromocytomas can be asymptomatic but may cause sustained or episodic hypertension. Pancreatic lesions often remain asymptomatic and rarely cause endocrine or exocrine insufficiency. Endolymphatic sac tumors can cause hearing loss of varying severity, which can be a presenting symptom. Cystadenomas of the epididymis are relatively common. They rarely cause problems, unless bilateral, in which case they may result in infertility.
Hirschsprung disease (HSCR), or congenital intestinal aganglionosis, is a birth defect characterized by complete absence of neuronal ganglion cells from a portion of the intestinal tract. The aganglionic segment includes the distal rectum and a variable length of contiguous proximal intestine. In 80% of individuals, aganglionosis is restricted to the rectosigmoid colon (short-segment disease); in 15%-20%, aganglionosis extends proximal to the sigmoid colon (long-segment disease); in about 5%, aganglionosis affects the entire large intestine (total colonic aganglionosis). Rarely, the aganglionosis extends into the small bowel or even more proximally to encompass the entire bowel (total intestinal aganglionosis). HSCR is considered a neurocristopathy, a disorder of cells and tissues derived from the neural crest, and may occur as an isolated finding or as part of a multisystem disorder. Affected infants frequently present in the first two months of life with symptoms of impaired intestinal motility such as failure to pass meconium within the first 48 hours of life, constipation, emesis, abdominal pain or distention, and occasionally diarrhea. However, because the initial diagnosis of HSCR may be delayed until late childhood or adulthood, HSCR should be considered in anyone with lifelong severe constipation. Individuals with HSCR are at risk for enterocolitis and/or potentially lethal intestinal perforation.
Pili bifurcati is an uncommon transitory hair shaft dysplasia with characteristic of segmental duplication of the hair shaft. Patients generally present with diffuse alopecia. Hypopigmentation can be observed. This anomaly of the hair shaft occurs in normal hair, pili canaliculi, or monilethrix and has been associated with the mosaic trisomy 8 syndrome, pseudomonilethrix type II or protein deficiency states. It can also be secondary to ulcerative colitis and extensive bowel resection. Caused by a transient duplication of the papilla's tip during the anagen phase, leading to the transitory production a two complete shafts, in the same follicular matrix, that emerge through a single pilary canal. When the two papilla tips fuse, both parallel branches form a single shaft again. When the transient duplication of the papilla tip occurs repetitively during the anagen phase, a series of bifurcation-fusion can be observed along the shaft. This situation is called pili multi-bifurcati. As a duplicated papilla tip can split again, a doubly bifurcated shaft may be observed: pili bi-bifurcati.
A condition observed in WOMEN and CHILDREN when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated ANDROGENS from the OVARIES, the ADRENAL GLANDS, or exogenous sources. The concept does not include HYPERTRICHOSIS, which is an androgen-independent excessive hair growth.
Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.
Any agent that binds to the histamine H1 receptor, thereby antagonizing histamine mediated allergic reactions, such as bronchoconstriction, vasodilation and up-regulated capillary permeability.
Any agent that competitively binds to and blocks the histamine H2 receptors found in the stomach, heart, uterus, on vascular smooth muscle and in the central nervous system (CNS). Of particular clinical relevance is the blockage of H2 receptors found on the parietal cells of the stomach, which prevents gastric acid secretion.
A semi-essential amino acid (children should obtain it from food) needed in humans for growth and tissue repair, Histidine is important for maintenance of myelin sheaths that protect nerve cells and is metabolized to the neurotransmitter histamine. Histamines play many roles in immunity, gastric secretion, and sexual functions. Histidine is also required for blood cell manufacture and protects tissues against damage caused by radiation and heavy metals. (NCI04)
The penultimate step in the pathway of histidine biosynthesis. Oxidation of the alcohol group on the side chain gives the acid group forming histidine. Histidinol has also been used as an inhibitor of protein synthesis.
Distinctive neoplastic disorders of histiocytes. Included are malignant neoplasms of MACROPHAGES and DENDRITIC CELLS.
A morphologic finding indicating tissue infiltration by non-neoplastic or neoplastic histiocytes.
Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the dysregulated proliferation of Langerhans cells and subsequent organ infiltration. Clinical manifestations range from a spontaneously healing isolated osteolytic lesion to a lymphoma-like syndrome with fatal multiorgan failure, in the absence of any cellular evidence of malignancy. Although the disease can present at any age, the peak age at diagnosis is between 1 and 3 years (summary by Arico et al., 1999). Egeler and D'Angio (1995) presented a classification of histiocytosis syndromes in children: class I, Langerhans cell histiocytosis (LCH); class II, histiocytosis of mononuclear macrophages other than Langerhans cells, including familial hemophagocytic lymphohistiocytosis (267700); and class III, malignant histiocytic disorders, including histiocytic lymphoma.
An antiquated term referring to cases of systemic non-Hodgkin lymphomas which are composed of large, atypical neoplastic lymphoid cells and cases of hemophagocytic syndromes. In the past, cases of anaplastic large cells lymphoma were called malignant histiocytosis.
Group of disorders which feature accumulations of active HISTIOCYTES and LYMPHOCYTES, but where the histiocytes are not LANGERHANS CELLS. The group includes HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; SINUS HISTIOCYTOSIS; xanthogranuloma; reticulohistiocytoma; JUVENILE XANTHOGRANULOMA; xanthoma disseminatum; as well as the lipid storage diseases (SEA-BLUE HISTIOCYTE SYNDROME; and NIEMANN-PICK DISEASES).
A morphologic finding indicating the presence of histiocytic infiltrates within distended lymph node sinuses.
A disease caused by the fungus Histoplasma capsulatum. It primarily affects the lungs but can also occur as a disseminated disease that affects additional organs. The acute respiratory disease has symptoms similar to those of a cold or flu and it usually resolves without treatment in healthy individuals. The disseminated form is generally fatal if untreated.
A disorder characterized by an enduring pattern of excessively intense and superficial emotionality, attention seeking behavior, seductive appearance and speech, self dramatization and/or theatrical behavior.
An infection caused by the human immunodeficiency virus.
HLA class II histocompatibility antigen, DR alpha chain (254 aa, ~29 kDa) is encoded by the human HLA-DRA gene. This protein plays a role in the presentation of antigen for recognition by CD4 T-cells.
Transmembrane proteins that form the beta subunits of the HLA-DR antigens. They are also referred to as the HLA-DR light chains.
An unnaturally deep or rough quality of voice.
Classic Hodgkin lymphoma is a lymph node cancer of germinal center B-cell origin. Hodgkin lymphoma tumors consist of a minority of malignant cells, known as 'Reed-Sternberg' (RS) cells, mixed with reactive lymphocytes and other benign inflammatory cells. A defining feature of RS cells is the presence of 2 nuclei (summary by Salipante et al., 2009).
A fluorescent dye of benzimidazole derivative. Pibenzimol binds to AT-specific sites in the minor groove of duplex DNA and inhibits topoisomerase I, and DNA polymerase, thereby preventing DNA replication. This agent prolongs the G2 phase of the cell cycle and initiates apoptosis in tumor cells. (NCI04)
An acute, highly contagious disease affecting swine of all ages and caused by the CLASSICAL SWINE FEVER VIRUS. It has a sudden onset with high morbidity and mortality.
Homocystinuria is an inherited disorder in which the body is unable to process certain building blocks of proteins (amino acids) properly. There are multiple forms of homocystinuria, which are distinguished by their signs and symptoms and genetic cause. The most common form of homocystinuria is characterized by nearsightedness (myopia), dislocation of the lens at the front of the eye, an increased risk of abnormal blood clotting, and brittle bones that are prone to fracture (osteoporosis) or other skeletal abnormalities. Some affected individuals also have developmental delay and learning problems.Less common forms of homocystinuria can cause intellectual disability, failure to grow and gain weight at the expected rate (failure to thrive), seizures, problems with movement, and a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic).The signs and symptoms of homocystinuria typically develop within the first year of life, although some mildly affected people may not develop features until later in childhood or adulthood.
An infection that is caused by hookworms.
An acute purulent infection of the sebaceous glands of Zeis at the base of the eyelashes, of the apocrine sweat glands of Moll or the meibomian sebacious glands often caused by staphylococcus infections. Hordeola can either occur as Hordeola externa affecting the sebaceous glands of Zeis or the apocrine sweat glands of Moll or as Hordeola interna affecting the meibomian sebacious glands. In contrast to chalazia, hordeola are extremely painful and can cause extreme local swelling.
Hordeola externa are acute purulent infections affecting the sebaceous glands of Zeis or the apocrine sweat glands of Moll, often caused by staphylococcus infections. In contrast to chalazia, hordeola are extremely painfull and can cause extreme local swelling.
Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.
A collective grouping for both naturally occurring and synthetic hormones, substitutes, and antagonists.
A syndrome associated with defective sympathetic innervation to one side of the face, including the eye. Clinical features include MIOSIS; mild BLEPHAROPTOSIS; and hemifacial ANHIDROSIS (decreased sweating)(see HYPOHIDROSIS). Lesions of the BRAIN STEM; cervical SPINAL CORD; first thoracic nerve root; apex of the LUNG; CAROTID ARTERY; CAVERNOUS SINUS; and apex of the ORBIT may cause this condition. (From Miller et al., Clinical Neuro-Ophthalmology, 4th ed, pp500-11)
Diseases of domestic and wild horses of the species Equus caballus.
The immune responses of a host to a graft. A specific response is GRAFT REJECTION.
SPTLC1-related hereditary sensory neuropathy (HSN) is an axonal form of hereditary motor and sensory neuropathy distinguished by prominent early sensory loss and later positive sensory phenomena including dysesthesia and characteristic ""lightning"" or ""shooting"" pains. Loss of sensation can lead to painless injuries, which, if unrecognized, result in slow wound healing and subsequent osteomyelitis requiring distal amputations. Motor involvement is present in all advanced cases and can be severe. After age 20 years, the distal wasting and weakness may involve proximal muscles, possibly leading to wheelchair dependency by the seventh or eighth decade. Sensorineural hearing loss is variable.
Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease.
Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common.
Hereditary sensory and autonomic neuropathy type V (HSAN5) is a condition that primarily affects the sensory nerve cells (sensory neurons), which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with HSAN5.The signs and symptoms of HSAN5 appear early, usually at birth or during infancy. People with HSAN5 lose the ability to feel pain, heat, and cold. Deep pain perception, the feeling of pain from injuries to bones, ligaments, or muscles, is especially affected in people with HSAN5. Because of the inability to feel deep pain, affected individuals suffer repeated severe injuries such as bone fractures and joint injuries that go unnoticed. Repeated trauma can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.
Infections caused by the HTLV or BLV deltaretroviruses. They include human T-cell leukemia-lymphoma (LEUKEMIA-LYMPHOMA, T-CELL, ACUTE, HTLV-I-ASSOCIATED).
Diseases caused by HUMAN T-LYMPHOTROPIC VIRUS 2.
The desire for FOOD generated by a sensation arising from the lack of food in the STOMACH.
Huntington disease (HD) is a progressive disorder of motor, cognitive, and psychiatric disturbances. The mean age of onset is 35 to 44 years and the median survival time is 15 to 18 years after onset.
The presence of a V-shaped indentation (notch) in the primary central incisor.
A respiratory distress syndrome in newborn infants, usually premature infants with insufficient PULMONARY SURFACTANTS. The disease is characterized by the formation of a HYALINE-like membrane lining the terminal respiratory airspaces (PULMONARY ALVEOLI) and subsequent collapse of the lung (PULMONARY ATELECTASIS).
A glucosaminoglycan consisting of D-glucuronic acid and N-acetyl-D-glucosamine disaccharide units that is a component of connective tissue, skin, vitreous humour, umbilical cord, synovial fluid and the capsule of certain microorganisms contributing to adhesion, elasticity, and viscosity of extracellular substances.
An enzyme that catalyzes the random hydrolysis of 1,4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate. (From Enzyme Nomenclature, 1992) There has been use as ANTINEOPLASTIC AGENTS to limit NEOPLASM METASTASIS.
A thioxanthene derivative of lucanthone with anti-schistosomal activity and potential antineoplastic activity. Hycanthone interferes with parasite nerve function, resulting in parasite paralysis and death. This agent also intercalates into DNA and inhibits RNA synthesis in vitro. (NCI04)
group of anticonvulsants containing an allantoin heterocyclic base.
Compounds based on imidazolidine dione. Some derivatives are ANTICONVULSANTS.
A gestational trophoblastic disorder characterized by marked enlargement of the chorionic villi, hyperplasia of the villous trophoblastic cells and hydropic changes.
A direct-acting vasodilator that is used as an antihypertensive agent.
A condition of abnormally high AMNIOTIC FLUID volume, such as greater than 2,000 ml in the LAST TRIMESTER and usually diagnosed by ultrasonographic criteria (AMNIOTIC FLUID INDEX). It is associated with maternal DIABETES MELLITUS; MULTIPLE PREGNANCY; CHROMOSOMAL DISORDERS; and congenital abnormalities.
A congenital condition where the greater portions of the cerebral hemispheres and CORPUS STRIATUM are replaced by CSF and glial tissue. The meninges and the skull are well formed, which is consistent with earlier normal embryogenesis of the telencephalon. Bilateral occlusions of the internal carotid arteries in utero is a potential mechanism. Clinical features include intact brainstem reflexes without evidence of higher cortical activity. (Menkes, Textbook of Child Neurology, 5th ed, p307)
A rare skin disorder of unknown etiology affecting children. It is a photodermatitis, characterized by the formation of vesicles and scarring on sun exposed areas.
A disorder characterized by an abnormal increase of cerebrospinal fluid in the ventricles of the brain.
A form of compensated hydrocephalus characterized clinically by a slowly progressive gait disorder (see GAIT DISORDERS, NEUROLOGIC), progressive intellectual decline, and URINARY INCONTINENCE. Spinal fluid pressure tends to be in the high normal range. This condition may result from processes which interfere with the absorption of CSF including SUBARACHNOID HEMORRHAGE, chronic MENINGITIS, and other conditions. (From Adams et al., Principles of Neurology, 6th ed, pp631-3)
A short acting thiazide diuretic. Hydrochlorothiazide (HCTZ) is widely used to treat hypertension and edema. This agent's metabolite appears to preferentially bind to and accumulate in red blood cells. This agent is primarily excreted by the kidneys.
A semisynthetic hydrogenated codeine derivative and opioid agonist with analgesic and antitussive effects. Hydrocodone primarily binds to and activates the mu-opioid receptor in the central nervous system (CNS). This leads to analgesia, euphoria, respiratory depression, miosis, decreased gastrointestinal motility, cough suppression and physical dependence. Hydrocodone is converted to hydromorphone by the cytochrome P450 enzyme CYP2D6.
A synthetic or semisynthetic analog of natural hydrocortisone hormone produced by the adrenal glands with primary glucocorticoid and minor mineralocorticoid effects. As a glucocorticoid receptor agonist, hydrocortisone promotes protein catabolism, gluconeogenesis, capillary wall stability, renal excretion of calcium, and suppresses immune and inflammatory responses. (NCI04)
A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p822)
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
Abnormal enlargement or swelling of a KIDNEY due to dilation of the KIDNEY CALICES and the KIDNEY PELVIS. It is often associated with obstruction of the URETER or chronic kidney diseases that prevents normal drainage of urine into the URINARY BLADDER.
A collection of fluid and gas within the pleural cavity. (Dorland, 27th ed)
A condition characterized by fluid accumulation in two or more anatomic compartments in the fetus.
Produced as an inhibitor, an antioxidant, and an intermediate in the synthesis of dyes, motor fuels, and oils; in photographic processing; and naturally in certain plant species, Hydroquinone is a phenol derivative with antioxidant properties that can cause toxicity in several organs, notably the kidney. Used as a topical treatment for skin hyperpigmentation and in various cosmetic products, it is metabolized mainly to glutathione conjugates and forms mutagenic DNA adducts in in-vitro systems. (NCI04)
A collection of watery fluid in the pleural cavity. (Dorland, 27th ed)
Injectable form of VITAMIN B 12 that has been used therapeutically to treat VITAMIN B 12 DEFICIENCY.
A 4-aminoquinoline with immunosuppressive, antiautophagy, and antimalarial activities. Although the precise mechanism of action is unknown, hydroxychloroquine may suppress immune function by interfering with the processing and presentation of antigens and the production of cytokines. As a lysosomotropic agent, hydroxychloroquine raises intralysosomal pH, impairing autophagic protein degradation; hydroxychloroquine-mediated accumulation of ineffective autophagosomes may result in cell death in tumor cells reliant on autophagy for survival. In addition, this agent is highly active against the erythrocytic forms of P. vivax and malariae and most strains of P. falciparum but not the gametocytes of P. falciparum.
Estrone derivatives substituted with one or more hydroxyl groups in any position. They are important metabolites of estrone and other estrogens.
A synthetic, nonionic hydroxyethyl derivative of starch used as a plasma expander when prepared in an isotonic solution. Upon intravenous administration, hydroxyethyl starch colloid increases blood volume and thus improves circulation. This agent is almost exclusively excreted by the kidneys and is potentially nephrotoxic.
Monohydroxyethyl derivative of rutin. Peripheral circulation stimulant used in treatment of venous disorders.
Inhibitor of DNA replication in gram-positive bacteria.
Metabolites or derivatives of PROGESTERONE with hydroxyl group substitution at various sites.
A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.
The 8-hydroxy derivatives inhibit various enzymes and their halogenated derivatives, though neurotoxic, are used as topical anti-infective agents, among other uses.
A monohydroxyl-substituted urea (hydroxycarbamate) antimetabolite. Hydroxyurea selectively inhibits ribonucleoside diphosphate reductase, an enzyme required to convert ribonucleoside diphosphates into deoxyribonucleoside diphosphates, thereby preventing cells from leaving the G1/S phase of the cell cycle. This agent also exhibits radiosensitizing activity by maintaining cells in the radiation-sensitive G1 phase and interfering with DNA repair. (NCI04)
A histamine H1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite CETIRIZINE, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative.
Aminoglycoside produced by Streptomyces hygroscopicus. It is used as an anthelmintic against swine infections by large roundworms, nodular worms, and whipworms.
A coumarin derivative possessing properties as a spasmolytic, choleretic and light-protective agent. It is also used in ANALYTICAL CHEMISTRY TECHNIQUES for the determination of NITRIC ACID.
A parasitic infection caused by tapeworms. Most infected individuals do not have symptoms. When symptoms appear, they include diarrhea, abdominal pain, restlessness, and irritability.
A condition caused by the overproduction of ALDOSTERONE. It is characterized by sodium retention and potassium excretion with resultant HYPERTENSION and HYPOKALEMIA.
A condition characterized by an abnormal increase of BILIRUBIN in the blood, which may result in JAUNDICE. Bilirubin, a breakdown product of HEME, is normally excreted in the BILE or further catabolized before excretion in the urine.
An inherited disorder affecting the metabolism of bilirubin. It results in increased levels of bilirubin in the blood. Representative examples of this condition include Gilbert syndrome and Crigler-Najjar syndrome.
Abnormally high concentration of calcium in the peripheral blood.
Abnormally high level of calcium in the urine.
A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood.
A regressive change of teeth characterized by excessive development of secondary cementum on the tooth surface. It may occur on any part of the root, but the apical two-thirds are most commonly affected. (Dorland, 27th ed)
A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.
Familial hypercholesterolemia (FH) is characterized by severely elevated LDL cholesterol (LDL-C) levels that lead to atherosclerotic plaque deposition in the coronary arteries and proximal aorta at an early age, leading to an increased risk for cardiovascular disease. Xanthomas (patches of yellowish cholesterol buildup) may worsen with age as a result of extremely high cholesterol levels. Xanthomas can occur around the eyelids and within the tendons of the elbows, hands, knees, and feet. In FH, the more common cardiovascular disease is coronary artery disease (CAD), which may manifest as angina and myocardial infarction; stroke occurs more rarely. Untreated men are at a 50% risk for a fatal or non-fatal coronary event by age 50 years; untreated women are at a 30% risk by age 60 years. An estimated 70%-95% of FH results from a heterozygous pathogenic variant in one of three genes (APOB, LDLR, PCSK9). FH is the most common inherited cardiovascular disease, with a prevalence of 1:200-250. FH likely accounts for 2%-3% of myocardial infarctions in individuals younger than age 60 years. In contrast, homozygous FH (HoFH) results from biallelic (homozygous or compound heterozygous) pathogenic variants in one of these known genes (APOB, LDLR, PCSK9). Most individuals with HoFH experience severe CAD by their mid-20s and the rate of either death or coronary bypass surgery by the teenage years is high. Severe aortic stenosis is also common.
Excessive vomiting in early pregnancy, leading to the loss of 5% or more of body weight.
The presence of an increased amount of blood in a body part or an organ leading to congestion or engorgement of blood vessels. Hyperemia can be due to increase of blood flow into the area (active or arterial), or due to obstruction of outflow of blood from the area (passive or venous).
Increased sensitivity to cutaneous stimulation due to a diminished threshold or an increased response to stimuli.
A laboratory test result indicating abnormally high concentrations of gamma globulins in the blood.
A serious complication of TYPE 2 DIABETES MELLITUS. It is characterized by extreme HYPERGLYCEMIA; DEHYDRATION; serum hyperosmolarity; and depressed consciousness leading to COMA in the absence of KETOSIS and ACIDOSIS.
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather. [HPO:probinson]
A syndrome with excessively high INSULIN levels in the BLOOD. It may cause HYPOGLYCEMIA. Etiology of hyperinsulinism varies, including hypersecretion of a beta cell tumor (INSULINOMA); autoantibodies against insulin (INSULIN ANTIBODIES); defective insulin receptor (INSULIN RESISTANCE); or overuse of exogenous insulin or HYPOGLYCEMIC AGENTS.
Abnormally high potassium concentration in the blood, most often due to defective renal excretion. It is characterized clinically by electrocardiographic abnormalities (elevated T waves and depressed P waves, and eventually by atrial asystole). In severe cases, weakness and flaccid paralysis may occur. (Dorland, 27th ed)
An elevated lipid concentration in the blood. [HPO:probinson]
APOE p.Leu167del is a rare genetic variant described in 38 cases in the literature with a range of clinical phenotypes. Three phenotypes can be associated with the APOE p.Leu167del variant: Inherited lipemic splenomegaly (also known as sea-blue histiocytosis) characterized by hypertriglyceridemia and splenomegaly. Variable manifestations include thrombocytopenia, liver function abnormalities, and cardiovascular disease. Autosomal dominant hypercholesterolemia (ADH) characterized by markedly elevated LDL cholesterol levels that leads to premature morbidity and mortality from atherosclerotic cardiovascular disease (ASCVD). Familial combined hyperlipidemia (FCHL) characterized by variable elevations of total cholesterol, triglycerides, or LDL cholesterol and a high risk of premature ASCVD. It has been suggested that the phenotype associated with the APOE p.Leu167del variant may depend on multiple factors, including sex, APOE genotype, control of hyperlipidemia, gene-gene interactions, gene-environment interactions, or perhaps epigenetic and other non-Mendelian effects.
An abnormal increase in the level of lipoprotein cholesterol in the blood.
Hyperlipoproteinemia type III, also called dysbetalipoproteinemia, is characterized by hyperlipidemia due to accumulation of remnants of the triglyceride (TG)-rich lipoproteins (TGRL), very low density lipoproteins (VLDL), and chylomicrons (CM), in response to dysfunctional genetic variants of apolipoprotein E or absence of apoE (summary by Blum, 2016).
Most individuals with familial hypertriglyceridemia have a hyperlipoproteinemia IV (144600) phenotype. Relatives of affected persons (ascertained in a study of survivors of coronary occlusion) were found to have normal cholesterol distribution and bimodal triglyceride distribution (Goldstein et al., 1973). Hypertriglyceridemia is not completely expressed in affected children. Genetic Heterogeneity of Hypertriglyceridemia Hypertriglyceridemia has many causes but, whatever its cause, there is evidence for its role as a coronary heart disease risk factor. Hypertriglyceridemia is commonly found in individuals with type II diabetes mellitus (125853). Several genetic bases for hypertriglyceridemia have been identified. Familial combined hyperlipidemia (HYPLIP1; 602491) is due to variation in the USF1 gene (191523) on chromosome 1q21-q23. Some mutations in the ABCA1 gene (600046) caused Tangier disease (205400), whereas others caused a mild disorder called type II familial high density lipoprotein deficiency, or hypoalphalipoproteinemia (604091). Both disorders are associated with hypertriglyceridemia.
A severe type of hyperlipidemia, sometimes familial, that is characterized by the elevation of both plasma CHYLOMICRONS and TRIGLYCERIDES contained in VERY-LOW-DENSITY LIPOPROTEINS. Type V hyperlipoproteinemia is often associated with DIABETES MELLITUS and is not caused by reduced LIPOPROTEIN LIPASE activity as in HYPERLIPOPROTEINEMIA TYPE I .
An abnormally increased sodium concentration in the blood.
A refractive error in which rays of light entering the eye parallel to the optic axis are brought to a focus behind the retina, as a result of the eyeball being too short from front to back. It is also called farsightedness because the near point is more distant than it is in emmetropia with an equal amplitude of accommodation. (Dorland, 27th ed)
Excessive growth or abnormal thickening of bone tissue.
A condition of unknown etiology characterized by thickening of the inner table of the frontal bone of the skull. It is seen more often in females and is usually bilateral.
An increase in the magnitude or amount of ossification of the skull.
Caffey disease is characterized by massive subperiosteal new bone formation (usually involving the diaphyses of the long bones as well as the ribs, mandible, scapulae, and clavicles) typically associated with fever, joint swelling, and pain in children, with onset around age two months and spontaneous resolution by age two years. On rare occasion, the hyperostosis can be detected by ultrasound examination late in the third trimester of pregnancy. Limited follow-up information suggests that adults who had Caffey disease in childhood may manifest joint laxity, skin hyperextensibility, hernias, and an increased risk for bone fractures and/or deformities.
A disease of elderly men characterized by large osteophytes that bridge vertebrae and ossification of ligaments and tendon insertions.
A rare, benign rheumatologic disorder or syndrome characterized by hyperostosis and soft tissue ossification between the clavicles and the anterior part of the upper ribs. It is often associated with the dermatologic disorder palmoplantar pustulosis, particularly in Japan. Careful diagnosis is required to distinguish it from psoriatic arthritis, OSTEITIS DEFORMANS, and other diseases. Spondylitis of pustulosis palmaris et plantaris is one of the possible causes; also, evidence suggests one origin may be bone infection. Bone imaging is especially useful for diagnosis. It was originally described by Sonozaki in 1974.
Primary hyperoxaluria is a rare condition characterized by recurrent kidney and bladder stones. The condition often results in end stage renal disease (ESRD), which is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.Primary hyperoxaluria results from the overproduction of a substance called oxalate. Oxalate is filtered through the kidneys and excreted as a waste product in urine, leading to abnormally high levels of this substance in urine (hyperoxaluria). During its excretion, oxalate can combine with calcium to form calcium oxalate, a hard compound that is the main component of kidney and bladder stones. Deposits of calcium oxalate can damage the kidneys and other organs and lead to blood in the urine (hematuria), urinary tract infections, kidney damage, ESRD, and injury to other organs. Over time, kidney function decreases such that the kidneys can no longer excrete as much oxalate as they receive. As a result oxalate levels in the blood rise, and the substance gets deposited in tissues throughout the body (systemic oxalosis), particularly in bones and the walls of blood vessels. Oxalosis in bones can cause fractures.There are three types of primary hyperoxaluria that differ in their severity and genetic cause. In primary hyperoxaluria type 1, kidney stones typically begin to appear anytime from childhood to early adulthood, and ESRD can develop at any age. Primary hyperoxaluria type 2 is similar to type 1, but ESRD develops later in life. In primary hyperoxaluria type 3, affected individuals often develop kidney stones in early childhood, but few cases of this type have been described so additional signs and symptoms of this type are unclear.
A condition of abnormally elevated output of PARATHYROID HORMONE (or PTH) triggering responses that increase blood CALCIUM. It is characterized by HYPERCALCEMIA and BONE RESORPTION, eventually leading to bone diseases. PRIMARY HYPERPARATHYROIDISM is caused by parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. SECONDARY HYPERPARATHYROIDISM is increased PTH secretion in response to HYPOCALCEMIA, usually caused by chronic KIDNEY DISEASES.
Abnormally elevated PARATHYROID HORMONE secretion as a response to HYPOCALCEMIA. It is caused by chronic KIDNEY FAILURE or other abnormalities in the controls of bone and mineral metabolism, leading to various BONE DISEASES, such as RENAL OSTEODYSTROPHY.
A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.
Disease of the glandular, anterior portion of the pituitary (PITUITARY GLAND, ANTERIOR) resulting in hypersecretion of ADENOHYPOPHYSEAL HORMONES such as GROWTH HORMONE; PROLACTIN; THYROTROPIN; LUTEINIZING HORMONE; FOLLICLE STIMULATING HORMONE ; and ADRENOCORTICOTROPIC HORMONE. Hyperpituitarism usually is caused by a functional ADENOMA.
An abnormal increase in the number of cells in an organ or a tissue with consequent enlargement.
Hyperprolactinemia unrelated to pregnancy occurs in approximately 0.1 to 0.3% of the general population and may result in infertility, hypogonadism, and galactorrhea. Such nonphysiologic hyperprolactinemia is caused mainly by drugs or by tumors in the anterior pituitary gland, primarily prolactinomas (see 102200). However, 10 to 60% of patients with hyperprolactinemia who undergo MRI have normal findings (summary by Newey et al., 2013). Patients with hyperprolactinemia may also experience agalactia (Kobayashi et al., 2018).
A pathological process initiated by exposure to a defined stimulus at a dose tolerated by normal persons. It may be the manifestation of a disposition to hypersensitivity.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability.
Disorders characterized by hypersomnolence during normal waking hours that may impair cognitive functioning. Subtypes include primary hypersomnia disorders (e.g., IDIOPATHIC HYPERSOMNOLENCE; NARCOLEPSY; and KLEINE-LEVIN SYNDROME) and secondary hypersomnia disorders where excessive somnolence can be attributed to a known cause (e.g., drug affect, MENTAL DISORDERS, and SLEEP APNEA SYNDROME). (From J Neurol Sci 1998 Jan 8;153(2):192-202; Thorpy, Principles and Practice of Sleep Medicine, 2nd ed, p320)
A malfunctioning of the spleen in which it prematurely destroys red blood cells.
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (145410), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
A condition of markedly elevated BLOOD PRESSURE with DIASTOLIC PRESSURE usually greater than 120 mm Hg. Malignant hypertension is characterized by widespread vascular damage, PAPILLEDEMA, retinopathy, HYPERTENSIVE ENCEPHALOPATHY, and renal dysfunction.
Abnormal increase of resistance to blood flow within the hepatic PORTAL SYSTEM, frequently seen in LIVER CIRRHOSIS and conditions with obstruction of the PORTAL VEIN.
Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.
Hypertension caused by narrowing or occlusion of the renal arteries.
High blood pressure secondary to renal artery stenosis.
A severe, acute increase in blood pressure that may result in stroke or myocardial ischemia.
An abnormality of thyroid physiology characterized by excessive secretion of the thyroid hormones thyroxine (i.e., T4) and/or 3,3',5-triiodo-L-thyronine zwitterion (i.e., triiodothyronine or T3).
Supranormal concentration of thyroxine in the blood.
Solutions that have a greater osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid.
Excessive hair growth anywhere on the body.
A condition of elevated levels of TRIGLYCERIDES in the blood.
Abnormal enlargement of a body part or organ.
Excessive enlargement of one or both breasts. Causes include pregnancy, obesity, and penicillamine therapy. It may result in neck, back, and shoulder pain.
A type of strabismus characterized by permanent upward deviation of the visual axis of one eye. [ORCID:0000-0003-0986-4123]
A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide.
A symptom complex resulting from ingesting excessive amounts of VITAMIN A.
Absent or reduced sensitivity to cutaneous stimulation.
Bleeding in the anterior chamber of the eye.
Any agent that depresses the central nervous system (CNS) and is used to induce calm and sleep.
A disorder characterized by a recurrent or persistent lack of desire for sexual activity. The lack of sexual desire is not attributable to another psychiatric disorder or to the physiological effects of substance use or a general medical condition.
A congenital or acquired condition of insufficient production of ALDOSTERONE by the ADRENAL CORTEX leading to diminished aldosterone-mediated synthesis of Na(+)-K(+)-EXCHANGING ATPASE in renal tubular cells. Clinical symptoms include HYPERKALEMIA, sodium-wasting, HYPOTENSION, and sometimes metabolic ACIDOSIS.
Conditions with abnormally low levels of BETA-LIPOPROTEINS (low density lipoproteins or LDL) in the blood. It is defined as LDL values equal to or less than the 5th percentile for the population. They include the autosomal dominant form involving mutation of the APOLIPOPROTEINS B gene, and the autosomal recessive form involving mutation of the microsomal triglyceride transfer protein. All are characterized by low LDL and dietary fat malabsorption.
An abnormally decreased calcium concentration in the blood.
An abnormally decreased calcium concentration in the urine.
A somatoform disorder in which an individual is preoccupied with having a serious illness despite not having been given a corroborating diagnosis.
Infestation with larvae of the genus Hypoderma, the warble fly.
Tooth agenesis in some form is a common human anomaly that affects approximately 20% of the population. Although tooth agenesis is associated with numerous syndromes, several case reports describe nonsyndromic forms that are either sporadic or familial in nature, as reviewed by Gorlin et al. (1990). The incidence of familial tooth agenesis varies with each class of teeth. Most commonly affected are third molars (wisdom teeth), followed by either upper lateral incisors or lower second premolars; agenesis involving first and second molars is very rare. Also see 114600 and 302400. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). Faulty use of the terms, however, have confounded their use. The term 'partial anodontia' is obsolete (Salinas, 1978). Genetic Heterogeneity of Selective Tooth Agenesis Other forms of selective tooth agenesis include STHAG2 (602639), mapped to chromosome 16q12; STHAG3 (604625), caused by mutation in the PAX9 gene (167416) on chromosome 14q12; STHAG4 (150400), caused by mutation in the WNT10A gene (606268) on chromosome 2q35; STHAG5 (610926), mapped to chromosome 10q11; STHAG7 (616724), caused by mutation in the LRP6 gene (603507) on chromosome 12p13; STHAG8 (617073), caused by mutation in the WNT10B gene (601906) on chromosome 12q13; STHAG9 (617275), caused by mutation in the GREM2 gene (608832) on chromosome 1q43; and STHAGX1 (313500), caused by mutation in the EDA gene (300451) on chromosome Xq13. A type of selective tooth agenesis that was formerly designated STHAG6 has been incorporated into the dental anomalies and short stature syndrome (DASS; 601216). Of 34 unrelated patients with nonsyndromic tooth agenesis, van den Boogaard et al. (2012) found that 56% (19 patients) had mutations in the WNT10A gene (STHAG4), whereas only 3% and 9% had mutations in the MSX1 (STHAG1) and PAX9 (STHAG3) genes, respectively. The authors concluded that WNT10A is a major gene in the etiology of isolated hypodontia. Genotype-Phenotype Correlations Yu et al. (2016) observed that the most frequently missing permanent teeth in WNT10B-associated oligodontia were the lateral incisors (83.3%), whereas premolars were missing only 51.4% of the time, which they noted was a pattern 'clearly different' from the oligodontia patterns resulting from WNT10A mutations. They also stated that the selective pattern in WNT10B mutants was different from that associated with mutations in other genes, such as MSX1, in which second premolars are missing, and PAX9, in which there is agenesis of molars.
A condition of less than normal MILK secretion.
A decreased concentration of glucose in the blood.
Substances which lower blood glucose levels.
Abnormally diminished capacity to sweat. [HPO:probinson]
Abnormally low potassium concentration in the blood. It may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. (Dorland, 27th ed)
An abnormal decrease in the level of lipoprotein cholesterol in the blood.
An abnormally decreased sodium concentration in the blood.
A condition caused by a deficiency of PARATHYROID HORMONE (or PTH). It is characterized by HYPOCALCEMIA and hyperphosphatemia. Hypocalcemia leads to TETANY. The acquired form is due to removal or injuries to the PARATHYROID GLANDS. The congenital form is due to mutations of genes, such as TBX1; (see DIGEORGE SYNDROME); CASR encoding CALCIUM-SENSING RECEPTOR; or PTH encoding parathyroid hormone.
A benign or malignant neoplasm that affects the hypopharynx.
Hypophosphatasia is characterized by defective mineralization of bone and/or teeth in the presence of low activity of serum and bone alkaline phosphatase. Clinical features range from stillbirth without mineralized bone at the severe end to pathologic fractures of the lower extremities in later adulthood at the mild end. Although the disease spectrum is a continuum, six clinical forms are usually recognized based on age at diagnosis and severity of features: Perinatal (severe) hypophosphatasia characterized by respiratory insufficiency and hypercalcemia. Perinatal (benign) hypophosphatasia with prenatal skeletal manifestations that slowly resolve into one of the milder forms. Infantile hypophosphatasia with onset between birth and age six months of rickets without elevated serum alkaline phosphatase activity. Childhood (juvenile) hypophosphatasia that ranges from low bone mineral density for age with unexplained fractures to rickets, and premature loss of primary teeth with intact roots. Adult hypophosphatasia characterized by stress fractures and pseudofractures of the lower extremities in middle age, sometimes associated with early loss of adult dentition. Odontohypophosphatasia characterized by premature exfoliation of primary teeth and/or severe dental caries without skeletal manifestations.
An inherited condition of abnormally low serum levels of PHOSPHATES (below 1 mg/liter) which can occur in a number of genetic diseases with defective reabsorption of inorganic phosphorus by the PROXIMAL RENAL TUBULES. This leads to phosphaturia, HYPOPHOSPHATEMIA, and disturbances of cellular and organ functions such as those in X-LINKED HYPOPHOSPHATEMIC RICKETS; OSTEOMALACIA; and FANCONI SYNDROME.
A condition of diminution or cessation of secretion of one or more hormones from the anterior pituitary gland. This may result from surgical or radiation ablation, non-secretory pituitary neoplasms, metastatic tumors, infarction, pituitary apoplexy, infiltrative or granulomatous processes, and other conditions.
A condition in which total serum protein level is below the normal range. Hypoproteinemia can be caused by protein malabsorption in the gastrointestinal tract, EDEMA, or PROTEINURIA.
Prothrombin deficiency is an extremely rare autosomal recessive bleeding disorder characterized by low levels of circulating prothrombin; it affects about 1 in 2,000,000 individuals. There are 2 main types: type I deficiency, known as true prothrombin deficiency or 'hypoprothrombinemia,' is defined as plasma levels of prothrombin being less than 10% of normal with a concomitant decrease in activity. These patients have severe bleeding from birth, including umbilical cord hemorrhage, hematomas, ecchymoses, hematuria, mucosal bleeding, hemarthroses, intracranial bleeding, gastrointestinal bleeding, and menorrhagia. Type II deficiency, known as 'dysprothrombinemia,' is characterized by normal or low-normal synthesis of a dysfunctional protein. Bleeding symptoms are more variable, depending on the amount of residual functional activity. Variant prothrombin gene alleles can result in 'hypoprothrombinemia' or 'dysprothrombinemia,' and individuals who are compound heterozygous for these 2 types of alleles have variable manifestations. Heterozygous mutation carriers, who have plasma levels between 40 and 60% of normal, are usually asymptomatic, but can show bleeding after tooth extraction or surgical procedures (review by Lancellotti and De Cristofaro, 2009).
Presence of pus (appears as a white fluid) producing a fluid level in the inferior part of the anterior chamber. []
Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.
A form of hypotension characterized by a sudden fall in blood pressure that occurs when a person assumes a standing position.
Neoplastic, inflammatory, infectious, and other diseases of the hypothalamus. Clinical manifestations include appetite disorders; AUTONOMIC NERVOUS SYSTEM DISEASES; SLEEP DISORDERS; behavioral symptoms related to dysfunction of the LIMBIC SYSTEM; and neuroendocrine disorders.
A primary or metastatic neoplasm that affects the hypothalamus.
A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.
Solutions that have a lesser osmotic pressure than a reference solution such as blood, plasma, or interstitial fluid.
A congenital condition, usually due to genetic aberrations, that is characterized by a lack of hair growth on the head and/or body.
A state of shock characterized by decreased circulating blood volume in relation to total vascular capacity. This type of shock is characterized by a reduction of diastolic filling pressures.
A psychological state of emotional lability characterized by irrational behavior. This is a colloquial term that is not commonly used in clinical medicine.
A disorder characterized by sudden, unexpected travel away from one's home or place of work accompanied by an inability to recall one's past; the individual is confused about his or her personal identity and may assume a new identity.
An inherited lysosomal storage disease characterized by the presence of dense intracytoplasmic inclusions in mesenchymal cells, especially fibroblasts. Signs and symptoms include developmental delay, psychomotor deterioration, and growth failure.
Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment.
One of several indole alkaloids extracted from Tabernanthe iboga, Baill. It has a complex pharmacological profile, and interacts with multiple systems of neurotransmission. Ibogaine has psychoactive properties and appears to modulate tolerance to opiates.
A nonsteroidal anti-inflammatory agent with analgesic properties used in the treatment of RHEUMATISM and ARTHRITIS.
A group of inherited or acquired skin disorders characterized by a dry, thickened, and scaly skin. The skin changes range from mild to severe.
Autosomal recessive congenital ichthyosis (ARCI) encompasses several forms of nonsyndromic ichthyosis. Although most neonates with ARCI are collodion babies, the clinical presentation and severity of ARCI may vary significantly, ranging from harlequin ichthyosis, the most severe and often fatal form, to lamellar ichthyosis (LI) and (nonbullous) congenital ichthyosiform erythroderma (CIE). These phenotypes are now recognized to fall on a continuum; however, the phenotypic descriptions are clinically useful for clarification of prognosis and management. Infants with harlequin ichthyosis are usually born prematurely and are encased in thick, hard, armor-like plates of cornified skin that severely restrict movement. Life-threatening complications in the immediate postnatal period include respiratory distress, feeding problems, and systemic infection. Collodion babies are born with a taut, shiny, translucent or opaque membrane that encases the entire body and lasts for days to weeks. LI and CIE are seemingly distinct phenotypes: classic, severe LI with dark brown, plate-like scale with no erythroderma and CIE with finer whiter scale and underlying generalized redness of the skin. Affected individuals with severe involvement can have ectropion, eclabium, scarring alopecia involving the scalp and eyebrows, and palmar and plantar keratoderma. Besides these major forms of nonsyndromic ichthyosis, a few rare subtypes have been recognized, such as bathing suit ichthyosis, self-improving collodion ichthyosis, or ichthyosis-prematurity syndrome.
A semisynthetic 4-demethoxy analogue of the antineoplastic anthracycline antibiotic daunorubicin. Idarubicin intercalates into DNA and interferes with the activity of topoisomerase II, thereby inhibiting DNA replication, RNA transcription and protein synthesis. Due to its high lipophilicity, idarubicin penetrates cell membranes more efficiently than other anthracycline antibiotic compounds.
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent.
A synthetic analogue of the nitrogen mustard cyclophosphamide with antineoplastic activity. Ifosfamide alkylates and forms DNA crosslinks, thereby preventing DNA strand separation and DNA replication. This agent is a prodrug that must be activated through hydroxylation by hepatic microsomal enzymes. (NCI04)
Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory IgA (IMMUNOGLOBULIN A, SECRETORY) is the main immunoglobulin in secretions.
An immunoglobulin isotype (subclass). This isotype is expressed on naive B cells along with IgM. Little is known about its physiologic role.
An immunoglobulin isotype (subclass) that characterizes secondary immune responses. This isotype is further broken down into several smaller subclasses (IgG1, IgG2a, IgG2b, IgG3 in the mouse; IgG1-4 in the human), and each subclass is differentially synthesized and secreted into the serum upon differential immune stimuli.
Pathological development in the ILEUM including the ILEOCECAL VALVE.
A benign or malignant neoplasm that affects the wall of the ileum. Representative examples include adenoma, carcinoma, and lymphoma.
Inflammation of any segment of the ILEUM and the ILEOCECAL VALVE.
The state of birth outside of wedlock. It may refer to the offspring or the parents.
A misperception of a real external stimulus.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
One of ANTIPROTOZOAL AGENTS used especially against BABESIA in livestock. Toxicity has been reported.
A synthetic tricyclic derivative, antidepressant Imipramine enhances monoamine neurotransmission in certain areas of the brain. It also induces sedation through histamine 1 receptor blockage; hypotension through beta-adrenergic blockage; and diverse parasympatholytic effects. Imipramine has less sedative effect than other members of its therapeutic family. It is used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. (NCI04)
Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides SERUM SICKNESS and the ARTHUS REACTION, evidence supports a pathogenic role for immune complexes in many other IMMUNE SYSTEM DISEASES including GLOMERULONEPHRITIS, systemic lupus erythematosus (LUPUS ERYTHEMATOSUS, SYSTEMIC) and POLYARTERITIS NODOSA.
A blood serum or immunoglobulin fraction that contains antibodies against specific antigens obtained from previously immunized animals.
An innate tolerance that prevents the body from attacking native proteins and tissue.
A mature T-cell non-Hodgkin lymphoma, characterized by systemic disease and a polymorphous infiltrate involving lymph nodes and extranodal sites. The clinical course is typically aggressive.
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.
A disorder resulting from an abnormality in the immune system.
Disorders characterized by abnormal proliferation of primary cells of the immune system or by excessive production of immunoglobulins.
A clonal disorder, also known as immunoproliferative small intestinal disease or Mediterranean lymphoma, characterised by the secretion of a defective alpha heavy chain. It predominantly affects young people in the Mediterranean region. It involves the small intestine, and patients usually present with malabsorption syndrome, abdominal pain, weight loss, and fever. There is extensive villous atrophy of the small intestinal mucosa, which is heavily infiltrated by small lymphocytes and plasma cells. The small intestinal morphologic changes are consistent with a mucosa-associated lymphoid tissue lymphoma (MALT lymphoma).
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
Agents comprised of various toxic molecules (Radioactive Isotopes and Bacterial or Plant Toxins) conjugated with specific immune substances (Immunoglobulins, Monoclonal Antibodies, and Antigens) that targets affected cells allowing incorporation of the toxin into the cells.
Blockage of the external auditory canal by a buildup of earwax.
A common superficial bacterial infection caused by STAPHYLOCOCCUS AUREUS or group A beta-hemolytic streptococci. Characteristics include pustular lesions that rupture and discharge a thin, amber-colored fluid that dries and forms a crust. This condition is commonly located on the face, especially about the mouth and nose.
A category of behaviors that can be loosely defined as the failure to resist an impulsive act or behavior that may be harmful to self or others.
Acting on the spur of the moment in response to immediate stimuli; acting on a momentary basis without a plan or consideration of outcomes; difficulty establishing or following plans; a sense of urgency and self-harming behavior under emotional distress.
Inadequate responses to physical, social, and emotional demands; general ineptness and instability, despite absence of actual physical or mental deficit.
A condition of HYPONATREMIA and renal salt loss attributed to overexpansion of BODY FLUIDS resulting from sustained release of ANTIDIURETIC HORMONES which stimulates renal resorption of water. It is characterized by normal KIDNEY function, high urine OSMOLALITY, low serum osmolality, and neurological dysfunction. Etiologies include ADH-producing neoplasms, injuries or diseases involving the HYPOTHALAMUS, the PITUITARY GLAND, and the LUNG. This syndrome can also be drug-induced.
Sexual intercourse between persons so closely related that they are forbidden by law to marry.
Involuntary passage of stool or urine from the body.
Incontinentia pigmenti (IP) is a disorder that affects the skin, hair, teeth, nails, eyes, and central nervous system; it occurs primarily in females and on occasion in males. Characteristic skin lesions evolve through four stages: I. Blistering (birth to age ~4 months). II. Wart-like rash (for several months). III. Swirling macular hyperpigmentation (age ~6 months into adulthood). IV. Linear hypopigmentation. Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Neovascularization of the retina, present in some individuals, predisposes to retinal detachment. Neurologic findings including seizures, intellectual disability, and developmental delays are occasionally seen.
A benzamide-sulfonamide-indole derived DIURETIC that functions by inhibiting SODIUM CHLORIDE SYMPORTERS.
A class of bicyclic organic compounds composed of a phenyl ring attached to a nitrogen-containing pyrrole ring. The chemical structure is C1(NC=C2)=C2C=CC=C1.
A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.
A drug that has analgesic and anti-inflammatory properties. Following reports of adverse reactions including reports of carcinogenicity in animal studies it was withdrawn from the market worldwide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p21)
An alpha-1 adrenergic antagonist that is commonly used as an antihypertensive agent.
Disorders caused by nutritional imbalance, either overnutrition or undernutrition, occurring in infants ages 1 month to 24 months.
A non-neoplastic or neoplastic disorder which occurs during the neonatal period.
Almost 1 of every 10 infants born in the United States are premature, or preemies. A premature birth is when a baby is born before 37 completed weeks of pregnancy. A full-term pregnancy is 40 weeks. Important growth and development happen throughout pregnancy - especially in the final months and weeks. Because they are born too early, preemies weigh much less than full-term babies. They may have health problems because their organs did not have enough time to develop. Problems that a baby born too early may have include. -Breathing problems. -Feeding difficulties. -Cerebral palsy. -Developmental delay. -Vision problems. -Hearing problems. Preemies need special medical care in a neonatal intensive care unit, or NICU. They stay there until their organ systems can work on their own. . Centers for Disease Control and Prevention.
Diseases that occur in PREMATURE INFANTS.
An infant having a birth weight lower than expected for its gestational age.
A localized pathological necrosis of tissue resulting from obstruction of the blood supply usually by a thrombus, an embolus, or vascular torsion.
invasion and growth of microorganisms in the kidney; may be clinically inapparent or result in local cellular injury.
A herpesvirus infection of CATTLE characterized by INFLAMMATION and NECROSIS of the mucous membranes of the upper RESPIRATORY TRACT.
A common, acute infection usually caused by the Epstein-Barr virus (HERPESVIRUS 4, HUMAN). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis.
Inflammation of the anatomical structures of the outer ear and ear canal secondary to an infectious process. Bacterial etiology is most common, but fungal infection is also possible. Symptoms include erythema, edema, and pain.
A reduced or absent capacity to reproduce.
Diminished or absent ability of a female to achieve conception.
The inability of the male to effect FERTILIZATION of an OVUM after a specified period of unprotected intercourse. Male sterility is permanent infertility.
A localized protective response resulting from injury or destruction of tissues. Inflammation serves to destroy, dilute, or wall off both the injurious agent and the injured tissue. In the acute phase, inflammation is characterized by the signs of pain, heat, redness, swelling, and loss of function. Histologically, inflammation involves a complex series of events, including dilatation of arterioles, capillaries, and venules, with increased permeability and blood flow; exudation of fluids, including plasma proteins; and leukocyte migration into the site of inflammation.
A granuloma that contains areas of necrosis. The majority of cases are of infectious origin.
A spectrum of small and large bowel inflammatory diseases of unknown etiology. It includes Crohn's disease, ulcerative colitis, and colitis of indeterminate type.
An acute viral infection in humans involving the respiratory tract. It is marked by inflammation of the NASAL MUCOSA; the PHARYNX; and conjunctiva, and by headache and severe, often generalized, myalgia.
Vaccines used to prevent infection by viruses in the family ORTHOMYXOVIRIDAE. It includes both killed and attenuated vaccines. The composition of the vaccines is changed each year in response to antigenic shifts and changes in prevalence of influenza virus strains. The flu vaccines may be mono- or multi-valent, which contains one or more INFLUENZAVIRUS A and INFLUENZAVIRUS B strains.
A benign or malignant neoplasm that occurs in brain parenchymal tissue below the tentorium cerebelli.
The protrusion of abdominal cavity contents through the inguinal canal, without mention of obstruction or necrosis of the herniated contents.
Illicit use of chemicals and products whose vapors can be inhaled to produce a rapid mind-altering effect. Inhalants include aerosols, gases, and volatile solvents that are often inhaled repeatedly to achieve the short-lived intoxicating effect.
Disorders caused by external forces rather than by physiologic dysfunction or by pathogens.
A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)
An inosine nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety.
A natural sugar found in cell membrane phospholipids, plasma lipoproteins, and (as the phosphate form) in the nucleus with potential chemopreventive properties. As one of a number of intracellular phosphate compounds, inositol is involved in cell signaling and may stimulate tumor cell differentiation. (NCI04)
Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition.
The maximum volume of air a subject can inhale into the lungs after a tidal exhalation (IRV plus TV).
The extra volume of air that can be inspired with maximal effort after reaching the end of a normal, quiet inspiration. Common abbreviation is IRV.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Compounds which inhibit or antagonize the biosynthesis or action of insulin.
A hypoglycemia-induced comatose state resulting from a large dose of exogenous insulin.
Decreased sensitivity to circulating insulin which may result in acanthosis nigicrans, elevated insulin level or hyperglycemia.
An intermediate-acting INSULIN preparation with onset time of 2 hours and duration of 24 hours. It is produced by crystallizing ZINC-insulin-PROTAMINES at neutral pH 7. Thus it is called neutral protamine Hagedorn for inventor Hans Christian Hagedorn.
A long-acting crystalline insulin often used in combination with a short-acting insulin in the treatment of diabetes mellitus. This type of insulin may be derived from porcine or recombinant sources. Administered once daily, insulin Lente starts to lower blood glucose within 1 to 3 hours after injection and exerts its peak effect 7 to 15 hours after injection. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats; it has anabolic effects on many types of tissues. (NCI04)
A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.
A non-glycosylated recombinant human alpha interferon, subtype 2a, produced in the bacterium E. coli. Interferon alpha-2a binds to its specific cell-surface receptor, resulting in the transcription and translation of genes whose protein products have antiviral, antiproliferative, anticancer, and immune modulating effects. (NCI04)
A non-glycosylated recombinant interferon with antiviral and antineoplastic activities. Alfa interferons bind to specific cell-surface receptors, resulting in the transcription and translation of genes whose protein products mediate antiviral, antiproliferative, anticancer, and immune-modulating effects.
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous lymphokine interferon gamma (IFN-gamma) with antineoplastic, immunoregulatory, and antiviral activities. Therapeutic IFN-gamma binds to and activates the cell-surface IFN-gamma receptor, stimulating antibody-dependent cytotoxicity and enhances natural killer cell attachment to tumor cells. This agent also activates caspases, thereby inducing apoptosis in malignant cells. (NCI04)
Agents that promote the production and release of interferons. They include mitogens, lipopolysaccharides, and the synthetic polymers Poly A-U and Poly I-C. Viruses, bacteria, and protozoa have been also known to induce interferons.
Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).
Interferon gamma (166 aa, ~19 kDa) is encoded by the human IFNG gene. This protein is involved in antiviral activity, macrophage activation, antiproliferative activity and immunopotentiation.
A cytokine produced by bone marrow stromal cells that promotes the growth of B-LYMPHOCYTE precursors and is co-mitogenic with INTERLEUKIN-2 for mature T-LYMPHOCYTE activation.
A symptom complex characterized by pain and weakness in SKELETAL MUSCLE group associated with exercise, such as leg pain and weakness brought on by walking. Such muscle limpness disappears after a brief rest and is often relates to arterial STENOSIS; muscle ISCHEMIA; and accumulation of LACTATE.
A disorder characterized by recurrent episodes of serious assaultive acts or destruction of property due to a failure to resist aggressive impulses; the degree of aggression during these episodes is grossly out of proportion to any psychosocial provocation. The aggressive episodes are not etiologically linked to another mental disorder, a general medical condition, or substance use.
Superficial dermatitis on opposed skin surfaces
An INTERVERTEBRAL DISC in which the NUCLEUS PULPOSUS has protruded through surrounding ANNULUS FIBROSUS. This occurs most frequently in the lower lumbar region.
A congenital malformation characterized by the absence of a normal opening in a part of the intestine. It can occur either in the small or the large intestine.
A classification of inherited or acquired disorders of sugar metabolism. Deficiencies of lactase, maltase or sucrase-isomaltase usually occur irreversibly and independent of one another. Congenital deficiencies are rare whereas acquired deficiencies are more common and may be seen following intestinal mucosal brush-border injury. Clinical signs include abdominal cramping, bloating, flatulence and diarrhea following dietary intake of lactose, maltose or sucrose. The clinical course leads to malabsorption of disaccharides which has implications for normal growth and development if manifested at an early age.
An abnormality of the intestine. The closely related term enteropathy is used to refer to any disease of the intestine.
Infections of the INTESTINES with PARASITES, commonly involving PARASITIC WORMS. Infections with roundworms (NEMATODE INFECTIONS) and tapeworms (CESTODE INFECTIONS) are also known as HELMINTHIASIS.
An abnormal anatomical passage between the INTESTINE, and another segment of the intestine or other organs. External intestinal fistula is connected to the SKIN (enterocutaneous fistula). Internal intestinal fistula can be connected to a number of organs, such as STOMACH (gastrocolic fistula), the BILIARY TRACT (cholecystoduodenal fistula), or the URINARY BLADDER of the URINARY TRACT (colovesical fistula). Risk factors include inflammatory processes, cancer, radiation treatment, and surgical misadventures (MEDICAL ERRORS).
A benign or malignant neoplasm involving the small or large intestine.
Any impairment, arrest, or reversal of the normal flow of INTESTINAL CONTENTS toward the ANAL CANAL.
A hole (perforation) in the wall of the intestine.
A discrete abnormal tissue mass that protrudes into the lumen of the intestine and is attached to the intestinal wall either by a stalk, pedunculus, or a broad base.
Infants with congenital short bowel syndrome are born with a shortened small intestine, with a mean length of 50 cm compared to the normal length of 190 to 280 cm, and intestinal malrotation. Severe malnutrition develops as a result of the hugely reduced absorptive surface of the small intestine, and infants require parenteral nutrition for survival; however, parenteral nutrition itself causes life-threatening complications such as sepsis and liver failure which are associated with a high rate of mortality early in life (summary by van der Werf et al., 2012).
An abscess that is located in the intracranial space.
A disease or disorder that occurs during the course of a surgical procedure.
A goiter that grows behind the STERNUM and CLAVICLE.
Spontaneous loss of INTRAUTERINE DEVICES from the UTERUS.
A glycoprotein secreted by the cells of the GASTRIC GLANDS that is required for the absorption of VITAMIN B 12 (cyanocobalamin). Deficiency of intrinsic factor leads to VITAMIN B 12 DEFICIENCY and ANEMIA, PERNICIOUS.
A form of intestinal obstruction caused by the PROLAPSE of a part of the intestine into the adjoining intestinal lumen. There are four types: colic, involving segments of the LARGE INTESTINE; enteric, involving only the SMALL INTESTINE; ileocecal, in which the ILEOCECAL VALVE prolapses into the CECUM, drawing the ILEUM along with it; and ileocolic, in which the ileum prolapses through the ileocecal valve into the COLON.
A naturally occurring, indigestible and non-absorbable oligosaccharide produced by certain plants with prebiotic and potential anticancer activity. Inulin stimulates the growth of beneficial bacteria in the colon, including Bifidobacteria and Lactobacilli, thereby modulating the composition of microflora. This creates an environment that protects against pathogens, toxins and carcinogens, which can cause inflammation and cancer. In addition, fermentation of inulin leads to an increase in short-chain fatty acids and lactic acid production, thereby reducing colonic pH, which may further control pathogenic bacteria growth and may contribute to inulin's cancer protective properties.
A type of chromosome rearrangement in which a segment has been turned through 180 degrees (inverted), and inserted back into its original location on the chromosome.
a turning inside-out positioning of a body part
A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically.
Iodinated derivatives of acetic acid. Iodoacetates are commonly used as alkylating sulfhydryl reagents and enzyme inhibitors in biochemical research.
A potentially neurotoxic 8-hydroxyquinoline derivative long used as a topical anti-infective, intestinal antiamebic, and vaginal trichomonacide. The oral preparation has been shown to cause subacute myelo-optic neuropathy and has been banned worldwide.
Complexes of iodine and non-ionic SURFACE-ACTIVE AGENTS acting as carrier and solubilizing agent for the iodine in water. Iodophors usually enhance bactericidal activity of iodine, reduce vapor pressure and odor, minimize staining, and allow wide dilution with water. (From Merck Index, 11th ed)
An ionic monomeric contrast medium that was formerly used for a variety of diagnostic procedures. (From Martindale, The Extra Pharmacopoeia, 30th ed, p706)
Reversible chemical reaction between a solid, often one of the ION EXCHANGE RESINS, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry.
A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.
Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes.
A non-ionic, water-soluble contrast agent which is used in myelography, arthrography, nephroangiography, arteriography, and other radiological procedures.
A syrup made from the dried rhizomes of two different species, CEPHAELIS ipecacuanha and C. acuminata. They contain EMETINE, cephaeline, psychotrine and other ISOQUINOLINES. Ipecac syrup is used widely as an emetic acting both locally on the gastric mucosa and centrally on the chemoreceptor trigger zone.
Ionic monomeric contrast media. Usually the sodium or calcium salts are used for examination of the gall bladder and biliary tract. (From Martindale, The Extra Pharmacopoeia, 30th ed, p704)
A tricyclic antidepressant that has actions and uses similar to those of AMITRIPTYLINE, but has only weak antimuscarinic and sedative effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p257)
An irreversible inhibitor of monoamine oxidase types A and B that is used as an antidepressive agent. It has also been used as an antitubercular agent, but its use is limited by its toxicity.
An antihistomonal agent with low toxicity. It also promotes growth and feed utilization in poultry.
A type of anterior uveitis, in which there is Inflammation of the iris and the ciliary body.
A non-neoplastic or neoplastic disorder that affects the iris.
A neoplasm that affects the iris. This category includes nevus and melanoma.
Organic chemicals that form two or more coordination links with an iron ion. Once coordination has occurred, the complex formed is called a chelate. The iron-binding porphyrin group of hemoglobin is an example of a metal chelate found in biological systems.
A colloidal solution containing ferric oxyhydroxide complexed with polymerized dextran, used as a form of parenteral iron-replacement therapy. Upon administration and absorption, the iron dextran complex is removed from plasma by the reticuloendothelial system which cleaves it into the components iron and dextran; ferric iron subsequently binds to transferrin or is stored as hemosiderin or ferritin. Transferrin-bound iron is transported in the plasma to the liver, spleen and bone marrow, where is it is incorporated into hemoglobin (Hgb) and to muscle where it is incorporated into myoglobin (Mb). Use of this agent circumvents the gastrointestinal adverse effects commonly encountered with the use of orally administered iron salt preparations. Because of cross-reactivity with antibodies targeted against polysaccharides similar to dextran, anaphylactic reactions may occur with this type of iron formulation.
A disorder with chronic or recurrent colonic symptoms without a clearcut etiology. This condition is characterized by chronic or recurrent ABDOMINAL PAIN, bloating, MUCUS in FECES, and an erratic disturbance of DEFECATION.
Abnormal or excessive excitability with easily triggered anger, annoyance, or impatience.
An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.
A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION.
A benign endocrine neoplasm arising from the pancreas. It is separated from the normal pancreatic tissues by a thin collagenous capsule. It may secrete a hormone (e.g. insulin, gastrin) or it may be non-functional.
A hydralazine and monoamine oxidase (MAO) inhibitor with antidepressant activity. Isocarboxazid blocks the breakdown (oxidative deamination) of biogenic amines by inhibiting MAO, thereby increasing the concentrations of norepinephrine and 5-hydroxytrytamine (5-HT) at central aminergic receptors. These neurotransmitters are involved in sustaining mood and emotions. The down-regulation of central beta-adrenergic and serotonergic receptors by chronic inhibition of MAO may also contribute to the antidepressant effects seen by isocarboxazid. (NCI05)
A beta-adrenergic receptor agonist with bronchodilator activity. Isoetharine selectively binds to beta-2 adrenergic receptors in bronchial smooth muscle, thereby activating intracellular adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, relieve bronchospasms, improve mucociliary clearance and reduce mediator substance release from inflammatory cells, especially from mast cells.
A class of polyphenolic compounds derived from the Fabaceae family with potential phytoestrogenic, cholesterol-reducing, chemotherapeutic and antioxidant activity. In isoflavones the phenyl group on the benzopyran ring is in position 3 relative to the oxygen of the ring. Most isoflavones for human consumption and that are currently studied are derived from soy beans.
A fluorinated ether with general anesthetic and muscle relaxant activities. Although the exact mechanism of action has not been established, inhaled isoflurane, appears to act on the lipid matrix of the neuronal cell membrane, which results in disruption of neuronal transmission. This agent enhances the release of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), thereby increasing the activity of the inhibitory neurotransmitter on synaptic transmission. Isoflurane may also both inhibit glutamatergic excitatory transmission by increasing glutamate re-uptake, and potentiate glycine receptor activity, which decreases motor function. In addition, isoflurane may alter certain pro- and anti-inflammatory cytokines, including interleukin-6 and -10 (IL-6, IL-10), possibly through the activation of the nuclear factor kappa B (NF-KB) pathway, which may affect immune responses during surgery.
An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels.
A synthetic derivative of nicotinic acid with anti-mycobacterial properties. Although its mechanism of action is still unclear, isoniazid appears to block the synthesis of mycolic acids, major components of the mycobacterial cell wall. This agent is only active against actively growing mycobacteria because, as a pro-drug, it requires activation in susceptible mycobacterial species. Isoniazid also interferes with mycobacterial metabolism of vitamin B6. Resistance occurs due to decreased bacterial wall penetration. (NCI04)
A formulation containing inosine, 4-acetamidobenzoic Acid, and N,N-dimethylaminoisopropanol, with immunomodulatory and antiviral activities. Although the exact mechanism of action is unknown, inosine pranobex appears to act as a thymus hormone analog; following administration, this agent may both induce T-cell differentiation and potentiate lymphoproliferative responses against transformed or virally-infected cells.
An isomer of 1-PROPANOL. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic.
A synthetic catechol compound and potent beta adrenergic agonist with peripheral vasodilator, bronchodilator, and cardiac stimulating properties. Isoproterenol exerts its effect on the beta-1 adrenergic receptors in the myocardium, thereby increasing heart rate and cardiac output. In addition, isoproterenol acts on beta-2 adrenergic receptors in bronchiolar and vascular smooth muscle, thereby causing smooth muscle relaxation.
1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma.
A vasodilator used in the treatment of ANGINA PECTORIS. Its actions are similar to NITROGLYCERIN but with a slower onset of action.
An undecenyl THIOUREA which may have topical anti-inflammatory activity.
Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. (From Grant & Hackh's Chemical Dictionary, 5th ed & Dorland, 28th ed)
A naturally-occurring retinoic acid with potential antineoplastic activity. Isotretinoin binds to and activates nuclear retinoic acid receptors (RARs); activated RARs serve as transcription factors that promote cell differentiation and apoptosis. This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby decreasing polyamine synthesis and keratinization.
A benzyl alcohol derivative with vasodilator activity. The mechanism of action of isoxsuprine hydrochloride is controversial, because isoxsuprine has beta-adrenergic activities that could not be offset by beta-adrenergic blockers. Although stimulation of the beta adrenergic receptor increases blood flow to produce vasodilatation, this agent may also have direct effects on the contractility of smooth muscle. Additionally, isoxsuprine causes relaxation of uterine smooth muscle and may also produce positive inotropic and chronotropic effects on the myocardium.
A large brown, blue, or gray hamartoma of dermal melanocytes, usually on the shoulder and upper arm that is most commonly found in Asian populations and in females. It is sometimes associated with sensory changes in the involved skin area, but very rarely becomes cancerous.
A macrocyclic lactone derived from Streptomyces avermitilis with antiparasitic activity. Ivermectin exerts its anthelmintic effect via activating glutamate-gated chloride channels expressed on nematode neurons and pharyngeal muscle cells. Distinct from the channel opening induced by endogenous glutamate transmitter, ivermectin-activated channels open very slowly but essentially irreversibly. As a result, neurons or muscle cells remain at either hyperpolarisation or depolarization state, thereby resulting in paralysis and death of the parasites. Ivermectin does not readily pass the mammal blood-brain barrier to the central nervous system where glutamate-gated chloride channels locate, hence the hosts are relatively resistant to the effects of this agent.
A partial motor seizure that begins in a single area of the body and progresses to include other areas on the same side of the body.
CLN2 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin between ages 2 and 4. The initial features usually include recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision loss. CLN2 disease affects motor skills, such as sitting and walking, and speech development. This condition also causes the loss of previously acquired skills (developmental regression), intellectual disability that gradually gets worse, and behavioral problems. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens.Some children with CLN2 disease do not develop symptoms until later in childhood, typically after age 4. These individuals tend to have milder features overall compared to those diagnosed earlier, but with more severe ataxia. They have a shortened life expectancy, although they tend to survive into adulthood.CLN2 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation ""CLN,"" meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype.
A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.
Dubin-Johnson syndrome is an autosomal recessive disorder characterized by conjugated hyperbilirubinemia, an increase in the urinary excretion of coproporphyrin isomer I, deposition of melanin-like pigment in hepatocytes, and prolonged retention of sulfobromophthalein, but otherwise normal liver function (summary by Wada et al., 1998).
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants.
A finding indicating increased bilirubin levels in the blood and urine, due to intrahepatic or extrahepatic obstruction of the biliary system.
Congenital absence of or defects in structures of the jaw.
A tumor originating in the jaw (mandible or maxilla).
The total absence of teeth from either the mandible or the maxilla, but not both. Total absence of teeth from both is MOUTH, EDENTULOUS. Partial absence of teeth in either is JAW, EDENTULOUS, PARTIALLY.
Absence of teeth from a portion of the mandible and/or maxilla.
Pathological development in the JEJUNUM region of the SMALL INTESTINE.
A benign or malignant neoplasm that affects the wall of the jejunum. Representative examples include adenoma, carcinoma, and lymphoma.
Jervell and Lange-Nielsen syndrome (JLNS) is characterized by congenital profound bilateral sensorineural hearing loss and long QTc, usually >500 msec. Prolongation of the QTc interval is associated with tachyarrhythmias, including ventricular tachycardia, episodes of torsade de pointes ventricular tachycardia, and ventricular fibrillation, which may culminate in syncope or sudden death. Iron-deficient anemia and elevated levels of gastrin are also frequent features of JLNS. The classic presentation of JLNS is a deaf child who experiences syncopal episodes during periods of stress, exercise, or fright. Fifty percent of individuals with JLNS had cardiac events before age three years. More than half of untreated children with JLNS die before age 15 years.
Lack of stability of a joint or joint prosthesis.
(2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.
A decapeptide bradykinin homolog cleaved from kininogen by kallikreins. It is a smooth-muscle stimulant and hypotensive agent that acts by vasodilatation.
Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77).
The most common mineral of a group of hydrated aluminum silicates, approximately H2Al2Si2O8-H2O. It is prepared for pharmaceutical and medicinal purposes by levigating with water to remove sand, etc. (From Merck Index, 11th ed) The name is derived from Kao-ling (Chinese: ""high ridge""), the original site. (From Grant & Hackh's Chemical Dictionary, 5th ed)
A disseminated vesicular-pustular eruption caused by the herpes simplex virus (HERPESVIRUS HOMINIS), the VACCINIA VIRUS, or Varicella zoster (HERPESVIRUS 3, HUMAN). It is usually superimposed on a preexisting, inactive or active, atopic dermatitis (DERMATITIS, ATOPIC).
Polysaccharide gum from Sterculia urens (STERCULIA). It is used as a suspending or stabilizing agent in foods, cosmetics and pharmaceuticals; a bulk-forming laxative; a surgical lubricant and adhesive; and in the treatment of skin ulcers.
A rare autosomal recessive inherited syndrome characterized by situs inversus, bronchiectasis, and chronic sinusitis. There is a defect in the function of the cilia that line the respiratory tract.
A mitochondrial disorder featuring the triad of chronic progressive EXTERNAL OPHTHALMOPLEGIA, cardiomyopathy (CARDIOMYOPATHIES) with conduction block (HEART BLOCK), and RETINITIS PIGMENTOSA. Disease onset is in the first or second decade. Elevated CSF protein, sensorineural deafness, seizures, and pyramidal signs may also be present. Ragged-red fibers are found on muscle biopsy. (Adams et al., Principles of Neurology, 6th ed, p984)
A form of herpetic keratitis characterized by the formation of small vesicles which break down and coalesce to form recurring dendritic ulcers, characteristically irregular, linear, branching, and ending in knoblike extremities. (Dictionary of Visual Science, 3d ed)
A benign, non-neoplastic, usually self-limiting epithelial lesion closely resembling squamous cell carcinoma clinically and histopathologically. It occurs in solitary, multiple, and eruptive forms. The solitary and multiple forms occur on sunlight exposed areas and are identical histologically; they affect primarily white males. The eruptive form usually involves both sexes and appears as a generalized papular eruption.
Inflammation of both the cornea and the conjunctiva.
Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with XEROSTOMIA and polyarthritis, it is called SJOGREN'S SYNDROME.
Infectious diseases of cattle, sheep, and goats, characterized by blepharospasm, lacrimation, conjunctivitis, and varying degrees of corneal opacity and ulceration. In cattle the causative agent is MORAXELLA (MORAXELLA) BOVIS; in sheep, MYCOPLASMA; RICKETTSIA; CHLAMYDIA; or ACHOLEPLASMA; in goats, RICKETTSIA.
Keratoconus is an eye condition that affects the shape of the cornea, which is the clear outer covering of the eye. In this condition, the cornea thins and bulges outward, eventually resembling a cone shape. These corneal abnormalities, which worsen over time, can lead to nearsightedness (myopia), blurred vision that cannot be improved with corrective lenses (irregular astigmatism), and vision loss.Other corneal changes typical of keratoconus that can be seen during an eye exam include iron deposits in the cornea that form a yellow-to-brownish ring, called the Fleischer ring, surrounding the colored part of the eye (iris). Affected individuals may also develop Vogt's striae, which are thin, vertical, white lines in the tissue at the back of the cornea.Keratoconus may affect only one eye at first, but eventually the corneas of both eyes become misshapen, although they might not be affected with the same severity. As keratoconus worsens, people with this condition can develop corneal scarring, often caused by exposure of the abnormally thin cornea to prolonged contact lens use or excessive eye rubbing.The eye changes characteristic of keratoconus typically begin in adolescence and slowly worsen until mid-adulthood at which point the shape of the cornea remains stable.
A skin disorder consisting of hypertrophy of the stratum corneum of the skin.
An autosomal dominant disorder characterized by a widely distributed, well-demarcated hyperkeratosis of the palms and soles. There is more than one genotypically distinct form, each of which is clinically similar but histologically distinguishable. Diffuse palmoplantar keratoderma is distinct from palmoplantar keratoderma (KERATODERMA, PALMOPLANTAR), as the former exhibits autosomal dominant inheritance and hyperhidrosis is frequently present.
Agents that soften, separate, and cause desquamation of the cornified epithelium or horny layer of skin. They are used to expose mycelia of infecting fungi or to treat corns, warts, and certain other skin diseases.
Any horny growth such as a wart or callus.
Darier-White disease, also known as keratosis follicularis, is an autosomal dominant skin disorder characterized by warty papules and plaques in seborrheic areas (central trunk, flexures, scalp, and forehead), palmoplantar pits, and distinctive nail abnormalities (Sakuntabhai et al., 1999). Onset is usually before the third decade, and penetrance is complete in adults, although expressivity is variable. Involvement may be severe, with widespread itchy malodorous crusted plaques, painful erosions, blistering, and mucosal lesions. Secondary infection is common. Sun, heat, and sweating exacerbate the symptoms. Darier disease never remits, but oral retinoids may reduce hyperkeratosis. Neuropsychiatric abnormalities, including mild mental retardation and epilepsy, have been described in association with Darier disease in a few families (Burge and Wilkinson, 1992); whether this is an association based on pleiotropism of the mutant gene or reflects coincidence is not clear. Histologic findings are (1) mild nonspecific perivascular infiltration in the dermis; (2) dermal villi protruding into the epidermis; (3) suprabasal detachment of the spinal layer leading to the formation of lacunae containing acantholytic cells; (4) in the more superficial epidermis, dyskeratotic round epidermal cells ('corps ronds'), the most distinctive feature; and (5) in the stratum corneum, 'grains' that resemble parakeratotic cells embedded in a hyperkeratotic horny layer. Electron microscopy reveals loss of desmosomal attachments, perinuclear aggregations of keratin filaments, and cytoplasmic vacuolization. Ultrastructural and immunologic studies suggest the disease results from an abnormality in the desmosome-keratin filament complex leading to a breakdown in cell adhesion.
Abnormal thickening of the skin of the palms of the hands and the soles of the feet.
A precancerous lesion of the skin composed of atypical keratinocytes. It is characterized by the presence of thick, scaly patches of skin. Several histologic variants have been described, including atrophic, acantholytic, and hyperkeratotic variants.
Seborrheic keratoses are common benign epidermal lesion that can develop on any part of the body.
A rare neurologic disorder occurring in infants with jaundice. It results from brain damage by existing high levels of unconjugated-indirect bilirubin.
A refined petroleum fraction used as a fuel as well as a solvent.
A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.
A quinazoline derivative and serotonin (5-hydroxytryptamine, 5HT) receptor subtype 2 (5-HTR2) antagonist with potential antihypertensive and antiplatelet activities. Following administration, ketanserin binds to and inhibits the signaling mediated by 5-HTR2, which inhibits serotonin-dependent vasoconstriction and platelet activation.
A synthetic derivative of phenylpiperazine with broad antifungal properties and potential antineoplastic activity. Ketoconazole inhibits sterol 14-a-dimethylase, a microsomal cytochrome P450-dependent enzyme, thereby disrupting synthesis of ergosterol, an important component of the fungal cell wall. (NCI04)
A propionic acid derivate and nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic effects. Ketoprofen inhibits the activity of the enzymes cyclo-oxygenase I and II, resulting in a decreased formation of precursors of prostaglandins and thromboxanes. The resulting decrease in prostaglandin synthesis, by prostaglandin synthase, is responsible for the therapeutic effects of ibuprofen. Ketoprofen also causes a decrease in the formation of thromboxane A2 synthesis, by thromboxane synthase, thereby inhibiting platelet aggregation.
A condition characterized by an abnormally elevated concentration of KETONE BODIES in the blood (acetonemia) or urine (acetonuria). It is a sign of DIABETES COMPLICATION, starvation, alcoholism or a mitochondrial metabolic disturbance (e.g., MAPLE SYRUP URINE DISEASE).
A cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis.
A vasodilator that also has bronchodilatory action. It has been employed in the treatment of angina pectoris, in the treatment of asthma, and in conjunction with ultraviolet light A, has been tried in the treatment of vitiligo. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1024)
Death of cells in the KIDNEY CORTEX, a common final result of various renal injuries including HYPOXIA; ISCHEMIA; and drug toxicity.
A nonspecific term referring to disease or damage of the kidneys. [HPO:curators]
Sudden loss of renal function, as manifested by decreased urine production, and a rise in serum creatinine or blood urea nitrogen concentration (azotemia).
Impairment of the renal function due to chronic kidney damage.
A benign or malignant neoplasm affecting the kidney. Representative examples of benign renal neoplasms include fibroma, lipoma, oncocytoma, and juxtaglomerular cell tumor. Representative examples of malignant renal neoplasms include renal cell carcinoma, renal pelvis carcinoma, Wilms tumor, rhabdoid tumor, sarcoma, and lymphoma.
A complication of kidney diseases characterized by cell death involving KIDNEY PAPILLA in the KIDNEY MEDULLA. Damages to this area may hinder the kidney to concentrate urine resulting in POLYURIA. Sloughed off necrotic tissue may block KIDNEY PELVIS or URETER. Necrosis of multiple renal papillae can lead to KIDNEY FAILURE.
Acute death of renal tubular cells that usually results from prolonged renal ischemia, nephrotoxins, or sepsis. The clinical course of acute tubular necrosis may be divided into initiation, maintenance, and recovery phases.
A usually autosomal dominant and less frequently autosomal recessive genetic disorder characterized by the presence of numerous cysts in the kidneys leading to end-stage renal failure. The autosomal dominant trait is associated with abnormalities on the short arm of chromosome 16. Symptoms in patients with the autosomal dominant trait usually appear at middle age and include abdominal pain, hematuria, and high blood pressure. Patients may develop brain aneurysms and liver cysts. Patients with the autosomal recessive trait present with progressive renal failure early in life and symptoms resulting from hepatic fibrosis. The autosomal recessive trait is associated with abnormalities of chromosome 6. Polycystic kidney disease may also result as a side effect in patients on renal dialysis.
A developmental disorder of the kidney characterized by cystic dilatation of the medullary collecting ducts, resulting in a spongy gross appearance of the kidney. It may be asymptomatic or complicated by hematuria, infections, or renal stones.
Morbus Kienboeck is a Juvenile aseptic necrosis affecting the Os lunatum.
Menkes disease is an X-linked recessive disorder characterized by generalized copper deficiency. The clinical features result from the dysfunction of several copper-dependent enzymes. De Bie et al. (2007) provided a detailed review of the molecular pathogenesis of Menkes disease.
Infections with bacteria of the genus KLEBSIELLA.
A disorder characterized by the recurrent failure to resist the impulse to steal items of little intrinsic value; the individual experiences a rising subjective sense of tension before the theft and a sense of gratification or relief during the theft.
Klinefelter syndrome is a chromosomal condition in boys and men that can affect physical and intellectual development. Most commonly, affected individuals are taller than average are unable to father biological children (infertile); however the signs and symptoms of Klinefelter syndrome vary among boys and men with this condition. In some cases, the features of the condition are so mild that the condition is not diagnosed until puberty or adulthood, and researchers believe that up to 75 percent of affected men and boys are never diagnosed.Boys and men with Klinefelter syndrome typically have small testes that produce a reduced amount of testosterone (primary testicular insufficiency). Testosterone is the hormone that directs male sexual development before birth and during puberty. Without treatment, the shortage of testosterone can lead to delayed or incomplete puberty, breast enlargement (gynecomastia), decreased muscle mass, decreased bone density, and a reduced amount of facial and body hair. As a result of the small testes and decreased hormone production, affected males are infertile but may benefit from assisted reproductive technologies. Some affected individuals also have differences in their genitalia, including undescended testes (cryptorchidism), the opening of the urethra on the underside of the penis (hypospadias), or an unusually small penis (micropenis).Other physical changes associated with Klinefelter syndrome are usually subtle. Older children and adults with the condition tend to be somewhat taller than their peers. Other differences can include abnormal fusion of certain bones in the forearm (radioulnar synostosis), curved pinky fingers (fifth finger clinodactyly), and flat feet (pes planus).Children with Klinefelter syndrome may have low muscle tone (hypotonia) and problems with coordination that may delay the development of motor skills, such as sitting, standing, and walking. Affected boys often have learning disabilities, resulting in mild delays in speech and language development and problems with reading. Boys and men with Klinefelter syndrome tend to have better receptive language skills (the ability to understand speech) than expressive language skills (vocabulary and the production of speech) and may have difficulty communicating and expressing themselves.Individuals with Klinefelter syndrome tend to have anxiety, depression, impaired social skills, behavioral problems such as emotional immaturity and impulsivity, attention deficit hyperactivity disorder (ADHD), and limited problem-solving skills (executive functioning). About 10 percent of boys and men with Klinefelter syndrome have autism spectrum disorder.Nearly half of all men with Klinefelter syndrome develop metabolic syndrome, which is a group of conditions that include type 2 diabetes, high blood pressure (hypertension), increased belly fat, high levels of fats (lipids) such as cholesterol and triglycerides in the blood. Compared with unaffected men, adults with Klinefelter syndrome also have an increased risk of developing involuntary trembling (tremors), breast cancer (if gynecomastia develops), thinning and weakening of the bones (osteoporosis), and autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. (Autoimmune disorders are a large group of conditions that occur when the immune system attacks the body's own tissues and organs.)
Klippel-Feil syndrome (KFS) is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae, resulting in a fused appearance. The clinical triad consists of short neck, low posterior hairline, and limited neck movement, although less than 50% of patients demonstrate all 3 clinical features (Tracy et al., 2004). Genetic Heterogeneity of Klippel-Feil Syndrome Additional forms of KFS include autosomal recessive KFS2 (214300), caused by mutation in the MEOX1 gene (600147) on chromosome 17q21, autosomal dominant KFS3 (613702), caused by mutation in the GDF3 gene (606522) on chromosome 12p13, and autosomal recessive KFS4 (616549), caused by mutation in the MYO18B gene (607295) on chromosome 22q12. See also MURCS association (601076), in which Klippel-Feil anomaly is associated with urogenital anomalies.
Klippel-Trenaunay syndrome is a condition that affects the development of blood vessels, soft tissues (such as skin and muscles), and bones. The disorder has three characteristic features: a red birthmark called a port-wine stain, abnormal overgrowth of soft tissues and bones, and vein malformations.Most people with Klippel-Trenaunay syndrome are born with a port-wine stain. This type of birthmark is caused by swelling of small blood vessels near the surface of the skin. Port-wine stains are typically flat and can vary from pale pink to deep maroon in color. In people with Klippel-Trenaunay syndrome, the port-wine stain usually covers part of one limb. The affected area may become lighter or darker with age. Occasionally, port-wine stains develop small red blisters that break open and bleed easily.Klippel-Trenaunay syndrome is also associated with overgrowth of bones and soft tissues beginning in infancy. Usually this abnormal growth is limited to one limb, most often one leg. However, overgrowth can also affect the arms or, rarely, the torso. The abnormal growth can cause pain, a feeling of heaviness, and reduced movement in the affected area. If the overgrowth causes one leg to be longer than the other, it can also lead to problems with walking.Malformations of veins are the third major feature of Klippel-Trenaunay syndrome. These abnormalities include varicose veins, which are swollen and twisted veins near the surface of the skin that often cause pain. Varicose veins usually occur on the sides of the upper legs and calves. Veins deep in the limbs can also be abnormal in people with Klippel-Trenaunay syndrome. Malformations of deep veins increase the risk of a type of blood clot called a deep vein thrombosis (DVT). If a DVT travels through the bloodstream and lodges in the lungs, it can cause a life-threatening blood clot known as a pulmonary embolism (PE).Other complications of Klippel-Trenaunay syndrome can include a type of skin infection called cellulitis, swelling caused by a buildup of fluid (lymphedema), and internal bleeding from abnormal blood vessels. Less commonly, this condition is also associated with fusion of certain fingers or toes (syndactyly) or the presence of extra digits (polydactyly).
A precancerous condition characterized by the presence of abnormal whitish areas on the glans or prepuce of the penis. Risk factors include chronic irritation, inflammation, and infection of the penis, and poor genital hygiene.
A chronic inflammatory disorder of unknown etiology that affects the vulva. It is characterized by the development of white elevated plaques in the vulva. Histologically there is marked subepithelial fibrosis. Clinical manifestations include pruritus, dysuria, and dyspareunia.
Metastatic signet-ring cell carcinoma to the ovary. The primary site is the gastrointestinal tract or breast.
A noble gas that is found in the atmosphere. It has the atomic symbol Kr, atomic number 36, atomic weight 83.80, and has been used in electric bulbs.
Adult-onset neuronal ceroid lipofuscinosis, also known as Kufs disease, is a neurodegenerative disorder without retinal involvement. There are 2 overlapping phenotypes: type A, characterized by progressive myoclonic epilepsy, and type B, characterized by dementia and a variety of motor-system signs (summary by Arsov et al., 2011). In general, the neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure. The ultrastructural pattern of lipopigment in CLN4 comprises a mixed pattern of 'granular,' 'curvilinear,' and 'fingerprint' profiles (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
A prion disease found exclusively among the Fore linguistic group natives of the highlands of NEW GUINEA. The illness is primarily restricted to adult females and children of both sexes. It is marked by the subacute onset of tremor and ataxia followed by motor weakness and incontinence. Death occurs within 3-6 months of disease onset. The condition is associated with ritual cannibalism, and has become rare since this practice has been discontinued. Pathologic features include a noninflammatory loss of neurons that is most prominent in the cerebellum, glial proliferation, and amyloid plaques. (From Adams et al., Principles of Neurology, 6th ed, p773)
A syndrome produced by severe protein deficiency, characterized by retarded growth, changes in skin and hair pigment, edema, and pathologic changes in the liver, including fatty infiltration, necrosis, and fibrosis. The word is a local name in Gold Coast, Africa, meaning ""displaced child"". Although first reported from Africa, kwashiorkor is now known throughout the world, but mainly in the tropics and subtropics. It is considered to be related to marasmus. (From Dorland, 27th ed)
Tick-borne flavivirus infection occurring in the Kyasanur Forest in India.
A broad-spectrum excitatory amino acid antagonist used as a research tool.
Abnormally increased curvature of the thoracic portion of the spine.
A salicylamide derivative that is a non-cardioselective blocker of BETA-ADRENERGIC RECEPTORS and ALPHA-1 ADRENERGIC RECEPTORS.
Any unintended event during the labor process that makes delivery more difficult.
The beginning of true OBSTETRIC LABOR which is characterized by the cyclic uterine contractions of increasing frequency, duration, and strength causing CERVICAL DILATATION to begin (LABOR STAGE, FIRST ).
Onset of OBSTETRIC LABOR before term (TERM BIRTH) but usually after the FETUS has become viable. In humans, it occurs sometime during the 29th through 38th week of PREGNANCY. TOCOLYSIS inhibits premature labor and can prevent the BIRTH of premature infants (INFANT, PREMATURE).
Accidentally acquired infection in laboratory workers.
Inflammation of the inner ear (LABYRINTH).
A non-neoplastic or neoplastic disorder that affects the lacrimal apparatus.
A disorder not necessarily related to pregnancy that is observed in females and males. It is characterized by disturbances of milk secretion. Causes include damage to the breast parenchyma due to inflammation, medications, pituitary tumors, and hypothyroidism.
An enzyme derived from cow's milk. It catalyzes the radioiodination of tyrosine and its derivatives and of peptides containing tyrosine.
A disaccharide (sugar) synthesized from fructose and galactose, Lactulose is used to treat constipation and some liver diseases. Nondigestible in mammals, lactulose passes unabsorbed down to the large intestine where resident bacteria consume it and produce lactic, acetic, and formic acids, which draw fluid into the bowel to soften the stool (laxative effect). Acidification of the colon contents attracts ammonia from the bloodstream, assisting stool excretion; helpful in liver failure when ammonia cannot be detoxified. (NCI04)
A rare autoimmune presynaptic disorder characterized by impairment of the impulse transmission at the neuromuscular junction. It affects predominantly the proximal muscles of the lower extremities, resulting in muscle weakness and fatigability. It has been associated with small cell lung carcinoma.
A departure from the normal gait in animals.
Glycosides from DIGITALIS lanata leaf. Lanatoside C has actions similar to DIGOXIN. Mixtures of lanatosides A, B, and C have also been used. (From Martindale, The Extra Pharmacopoeia, 30th ed, p670)
Trichorhinophalangeal syndrome (TRPS) comprises TRPS I (caused by a heterozygous pathogenic variant in TRPS1) and TRPS II (caused by contiguous gene deletion of TRPS1, RAD21, and EXT1). Both types of TRPS are characterized by distinctive facial features; ectodermal features (fine, sparse, depigmented, and slow growing hair; dystrophic nails; and small breasts); and skeletal findings (short stature; short feet; brachydactyly with ulnar or radial deviation of the fingers; and early, marked hip dysplasia). TRPS II is characterized by multiple osteochondromas (typically first observed clinically on the scapulae and around the elbows and knees between ages 1 month and 6 years) and an increased risk of mild-to-moderate intellectual disability.
Conditions characterized by language abilities (comprehension and expression of speech and writing) that are below the expected level for a given age, generally in the absence of an intellectual impairment. These conditions may be associated with DEAFNESS; BRAIN DISEASES; MENTAL DISORDERS; or environmental factors.
A category of disorders characterized by an impairment in the development of an individual's language capabilities, which is in contrast to his/her non-verbal intellect.
A yellow fat obtained from sheep's wool. It is used as an emollient, cosmetic, and pharmaceutic aid.
A silvery white metallic element that belongs to period 6 of the lanthanoids family, with phosphate binding property. Lanthanum, when administered in a salt form, dissociates in acid to release lanthanum ions, which then bind dietary phosphate. This agent inhibits the absorption of phosphate by forming highly insoluble lanthanum-phosphate complexes that reduce concentrations of serum phosphate and calcium phosphate.
The hydrochloride salt form of propiomazine, a phenothiazine derivative and atypical antipsychotic agent with sedative, antiemetic and antipsychotic activities. Propiomazine binds to a variety of receptors, including alpha1, dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors. Propiomazine exerts its antiemetic and sedative effects through antagonism at histamine H1 receptors; Its antipsychotic effect is attributed to antagonistic activities at dopamine and 5-HT2 receptors.
Infections caused by nematode larvae which never develop into the adult stage and migrate through various body tissues. They commonly infect the skin, eyes, and viscera in man. Ancylostoma brasiliensis causes cutaneous larva migrans. Toxocara causes visceral larva migrans.
A condition produced in man by the prolonged migration of animal nematode larvae in extraintestinal tissues other than skin; characterized by persistent hypereosinophilia, hepatomegaly, and frequently pneumonitis, commonly caused by Toxocara canis and Toxocara cati.
A non-neoplastic or neoplastic disorder that affects the larynx. Representative examples include laryngitis, vocal cord polyp, squamous papilloma, and carcinoma.
Abnormal accumulation of fluid in tissues of any part of the LARYNX, commonly associated with laryngeal injuries and allergic reactions.
A benign or malignant neoplasm involving the larynx.
Inflammation of LARYNGEAL CARTILAGES, usually due to infections.
A spasm (involuntary contraction) of the vocal cords that can make it difficult to speak or breathe.
An acute or chronic, bacterial or viral inflammatory process affecting the larynx. Signs and symptoms include sore throat, cough, swallowing difficulties, and hoarseness.
Developmental or acquired stricture or narrowing of the LARYNX. Symptoms of respiratory difficulty depend on the degree of laryngeal narrowing.
A viral hemorrhagic fever that is caused by the Lassa virus, which is transmitted by contact with infected rodents; it is characterized by fever, headache, malaise, myalgia, and hearing loss.
PNPLA6-related disorders span a phenotypic continuum characterized by variable combinations of cerebellar ataxia, upper motor neuron involvement manifesting as spasticity and/or brisk reflexes, chorioretinal dystrophy associated with variable degrees of reduced visual function, and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics), either in isolation or as part of anterior hypopituitarism (growth hormone, thyroid hormone, or gonadotropin deficiencies). Common but less frequent features are peripheral neuropathy (usually of axonal type manifesting as reduced distal reflexes, diminished vibratory sensation, and/or distal muscle wasting), hair anomalies (long eyelashes, bushy eyebrows, or scalp alopecia), short stature, and impaired cognitive functioning (learning disabilities in children and deficits in attention, visuospatial abilities, and recall in adults). Some of these features can occur in distinct clusters on the phenotypic continuum: Boucher-Neuhäuser syndrome (cerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism); Gordon Holmes syndrome (cerebellar ataxia, hypogonadotropic hypogonadism, and – to a variable degree – brisk reflexes); Oliver-McFarlane syndrome (trichomegaly, chorioretinal dystrophy, short stature, intellectual disability, and hypopituitarism); Laurence-Moon syndrome; and spastic paraplegia type 39 (SPG39) (upper motor neuron involvement, peripheral neuropathy, and sometimes reduced cognitive functioning and/or cerebellar ataxia).
Discharge of cerebrospinal fluid through a hole through the skull bone most commonly draining from the nose (CEREBROSPINAL FLUID RHINORRHEA) or the ear (CEREBROSPINAL FLUID OTORRHEA).
A group of disorders that affect a person's ability to learn or process specific types of information which is in contrast to his/her apparent level of intellect.
Lecithin:cholesterol acyltransferase deficiency is a disorder of lipoprotein metabolism and causes a typical triad of diffuse corneal opacities, target cell hemolytic anemia, and proteinuria with renal failure.
A conduction block of the left branch of the bundle of His. This manifests as a generalized disturbance of QRS morphology on EKG.
Failure of adequate output by the left ventricle despite an increase in distending pressure and in end-diastolic volume, with dyspnea, orthopnea, and other signs and symptoms of pulmonary congestion and edema.
An involuntary contraction of a muscle supporting the femur.
A nonspecific term used to denote any cutaneous lesion or group of lesions, or eruptions of any type on the leg. (From Stedman, 25th ed)
A condition in which one of a pair of legs fails to grow as long as the other, which could result from injury or surgery.
A sensation of discomfort emanating from the femur or its supporting structures.
A circumscribed, inflammatory, and often suppurating lesion that causes necrosis of tissue on the skin of the limb comprising the hip, thigh, leg and foot.
Legg-Calve-Perthes disease is characterized by loss of circulation to the femoral head, resulting in avascular necrosis in a growing child. Clinical pictures of the disease vary, depending on the phase of disease progression through ischemia, revascularization, fracture and collapse, and repair and remodeling of the bone. The disease occurs more frequently in boys, and most patients tend to be shorter than their peers. Both familial and isolated cases of LCPD have been reported (summary by Chen et al., 2004).
Any disease caused by Legionella bacteria.
A pneumonia caused by Legionella pneumophila and other Legionella species, which is characterized by fever, cough, progressive respiratory distress, and which is often accompanied by extrapulmonary manifestations.
Leigh syndrome is a clinically and genetically heterogeneous disorder resulting from defective mitochondrial energy generation. It most commonly presents as a progressive and severe neurodegenerative disorder with onset within the first months or years of life, and may result in early death. Affected individuals usually show global developmental delay or developmental regression, hypotonia, ataxia, dystonia, and ophthalmologic abnormalities, such as nystagmus or optic atrophy. The neurologic features are associated with the classic findings of T2-weighted hyperintensities in the basal ganglia and/or brainstem on brain imaging. Leigh syndrome can also have detrimental multisystemic affects on the cardiac, hepatic, gastrointestinal, and renal organs. Biochemical studies in patients with Leigh syndrome tend to show increased lactate and abnormalities of mitochondrial oxidative phosphorylation. Thus, Leigh syndrome may be a clinical feature of a primary deficiency of any of the mitochondrial respiratory chain complexes: complex I deficiency (see 252010), complex II deficiency (see 252011), complex III deficiency (see 124000), complex IV deficiency (cytochrome c oxidase; see 220110), or complex V deficiency (see 604273) (summary by Lake et al., 2015). Genetic Heterogeneity of Leigh Syndrome Mutations in complex I genes include mitochondrial-encoded MTND2 (516001), MTND3 (516002), MTND5 (516005), and MTND6 (516006), the nuclear-encoded NDUFS1 (157655), NDUFS3 (603846), NDUFS4 (602694), NDUFS7 (601825), NDUFS8 (602141), NDUFA2 (602137), NDUFA9 (603834), NDUFA10 (603835), NDUFA12 (614530), NDUFAF6 (612392), and NDUFAF5 (612360). Mutation in the MTFMT gene (611766), which is involved in mitochondrial translation, has also been reported with complex I deficiency. A mutation has been found in a complex III gene: BCS1L (603647), which is involved in the assembly of complex III. Mutations in complex IV genes include mitochondrial-encoded MTCO3 (516050) and nuclear-encoded COX10 (602125), COX15 (603646), SCO2 (604272), SURF1 (185620), which is involved in the assembly of complex IV, TACO1 (612958), and PET100 (614770). A mutation has been found in a complex V gene: the mitochondrial-encoded MTATP6 (516060). Mutations in genes encoding mitochondrial tRNA proteins have also been identified in patients with Leigh syndrome: see MTTV (590105), MTTK (590060), MTTW (590095), and MTTL1 (590050). Leigh syndrome may also be caused by mutations in components of the pyruvate dehydrogenase complex (e.g., DLD, 238331 and PDHA1, 300502). The French Canadian (or Saguenay-Lac-Saint-Jean) type of Leigh syndrome with COX deficiency (LSFC; 220111) is caused by mutation in the LRPPRC gene (607544). Deficiency of coenzyme Q10 (607426) can present as Leigh syndrome.
A well-circumscribed benign smooth muscle neoplasm characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A sarcoma containing large spindle cells of smooth muscle. Although it rarely occurs in soft tissue, it is common in the viscera. It is the most common soft tissue sarcoma of the gastrointestinal tract and uterus. The median age of patients is 60 years. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p1865)
A disease caused by any of a number of species of protozoa in the genus LEISHMANIA. There are four major clinical types of this infection: cutaneous (Old and New World) (LEISHMANIASIS, CUTANEOUS), diffuse cutaneous (LEISHMANIASIS, DIFFUSE CUTANEOUS), mucocutaneous (LEISHMANIASIS, MUCOCUTANEOUS), and visceral (LEISHMANIASIS, VISCERAL).
An endemic disease that is characterized by the development of single or multiple localized lesions on exposed areas of skin that typically ulcerate. The disease has been divided into Old and New World forms. Old World leishmaniasis is separated into three distinct types according to epidemiology and clinical manifestations and is caused by species of the L. tropica and L. aethiopica complexes as well as by species of the L. major genus. New World leishmaniasis, also called American leishmaniasis, occurs in South and Central America and is caused by species of the L. mexicana or L. braziliensis complexes.
An acute necrotizing form of cutaneous leishmaniasis caused by Infection with leishmania tropica major.
A chronic disease caused by LEISHMANIA DONOVANI and transmitted by the bite of several sandflies of the genera Phlebotomus and Lutzomyia. It is commonly characterized by fever, chills, vomiting, anemia, hepatosplenomegaly, leukopenia, hypergammaglobulinemia, emaciation, and an earth-gray color of the skin. The disease is classified into three main types according to geographic distribution: Indian, Mediterranean (or infantile), and African.
Any disease affecting the lens of the eye.
Complete dislocation of the lens of the eye.
A partial dislocation of the lens of the eye.
A flat, benign, pigmented spot on the skin caused by excessive deposition of melanin from an increased number of melanocytes in the cell layer directly above the basement membrane of the epidermis. Formation is usually related to sun exposure during youth, and the lesions do not typically progress to malignancy.
Polysaccharide isolated from the edible mushroom LENTINULA EDODES. The exact composition is unknown.
Substances that suppress Mycobacterium leprae, ameliorate the clinical manifestations of leprosy, and/or reduce the incidence and severity of leprous reactions.
A bacterial granulomatous infection caused by Mycobacterium leprae. It is a progressive disease affecting the skin, peripheral nerves, and limbs. If untreated, it causes permanent tissue damage leading to autoamputations.
A form of LEPROSY in which there are clinical manifestations of both principal types (lepromatous and tuberculoid). The disease may shift toward one of these two polar or principal forms.
A chronic communicable infection which is a principal or polar form of LEPROSY. This disorder is caused by MYCOBACTERIUM LEPRAE and produces diffuse granulomatous skin lesions in the form of nodules, macules, or papules. The peripheral nerves are involved symmetrically and neural sequelae occur in the advanced stage.
A principal or polar form of LEPROSY in which the skin lesions are few and are sharply demarcated. Peripheral nerve involvement is pronounced and may be severe. Unlike lepromatous leprosy (LEPROSY, LEPROMATOUS), the lepromin test is positive. Tuberculoid leprosy is rarely a source of infection to others.
A contagious bacterial infection caused by spirochetes of the genus Leptospira. Humans are infected by contact with water and soil which have been contaminated with animal waste products. The signs and symptoms include an initial flu-like phase, followed by a second phase in which patients may develop meningitis, liver failure and renal failure.
A condition caused by occlusion of terminal aorta, the primary branches of the ABDOMINAL AORTA, as in aortoiliac obstruction. Leriche syndrome usually occurs in males and is characterized by IMPOTENCE, absence of a pulse in the femoral arteries, weakness and numbness in the lower back, buttocks, hips, and lower limbs.
Lesch-Nyhan syndrome is characterized by motor dysfunction that resembles cerebral palsy, cognitive and behavioral disturbances, and uric acid overproduction (hyperuricemia). The most common presenting features, hypotonia and developmental delay, are evident by age three to six months. Affected children are delayed in sitting and most never walk. Within the first few years, extrapyramidal involvement (e.g., dystonia, choreoathetosis, opisthotonos) and pyramidal involvement (e.g., spasticity, hyperreflexia, extensor plantar reflexes) become evident. Cognitive impairment and behavioral disturbances emerge between ages two and three years. Persistent self-injurious behavior (biting the fingers, hands, lips, and cheeks; banging the head or limbs) is a hallmark of the disease. Overproduction of uric acid may lead to deposition of uric acid crystals or calculi in the kidneys, ureters, or bladder. Gouty arthritis may occur later in the disease. Related disorders with less severe manifestations include hyperuricemia with neurologic dysfunction but no self-injurious behavior and hyperuricemia alone, sometimes with acute renal failure.
A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to DEPRESSION or DRUG ADDICTION.
A multifocal, multisystem form of Langerhans-cell histiocytosis. There is involvement of multiple organ systems including the bones, skin, liver, spleen, and lymph nodes. Patients are usually infants presenting with fever, hepatosplenomegaly, lymphadenopathy, bone and skin lesions, and pancytopenia.
An essential branched-chain amino acid important for hemoglobin formation.
A derivative of folic acid with chemoprotectant, antidote and synergistic activity. Leucovorin does not require metabolism by dihydrofolate reductase, the molecular target of folate antagonist-type chemotherapeutic drugs, and is converted to a tetrahydrofolate, which is the necessary folate for purine and pyrimidine synthesis. As this agent allows for some purine/pyrimidine synthesis to occur, the toxic effects of folic acid antagonist-type chemotherapeutic drugs are counteracted while still permitting the antitumor activity of the folic acid antagonist through dihydrofolate reductase inhibition. This agent also potentiates the effects of 5-fluorouracil and its derivatives by stabilizing the binding of 5-fluorouracil's converted form fluorodeoxyuridylic acid to its target enzyme thymidylate synthase, thus prolonging drug activity.
A cancer of the blood and bone marrow characterized by an abnormal proliferation of leukocytes.
An experimental LYMPHOCYTIC LEUKEMIA of mice.
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.
Chronic lymphocytic leukemia (CLL) is a common neoplasia of B lymphocytes in which these cells progressively accumulate in the bone marrow, blood, and lymphoid tissues. The clinical evolution of the disorder is heterogeneous, with some patients having indolent disease and others having aggressive disease and short survival (summary by Quesada et al., 2012). Genetic Heterogeneity of Susceptibility to Chronic Lymphocytic Leukemia Susceptibility loci have been mapped to chromosomes 11p11 (CLLS1; 609630) and 13q14 (CLLS2; 109543) by genomewide linkage analysis and translocation studies, respectively. Susceptibility mapping to chromosome 9q34 (CLLS3; 612557) is associated with downregulation of the DAPK1 gene (600831). Genomewide association studies have identified susceptibility loci on chromosomes 6p25.3 (CLLS4; 612558) and 11q24.1 (CLLS5; 612559).
A rare acute myeloid leukemia in which the immature cells differentiate towards basophils.
Acute lymphoblastic leukemia which is positive for the common acute lymphoblastic leukemia antigen.
A poorly defined concept which at best is described as an extremely rare entity, possibly related to various subtypes of acute myeloid leukemia with abnormal eosinophils. (WHO, 2001)
A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.
A neoplasm of small B-lymphocytes with ""hairy"" projections in bone marrow, spleen, and peripheral blood. Most patients present with splenomegaly and pancytopenia. (WHO, 2001)
A malignant lymphocytic neoplasm of B-cell or T-cell lineage involving primarily the bone marrow and the peripheral blood. This category includes precursor or acute lymphoblastic leukemias and chronic leukemias.
Acute lymphoblastic leukemia (ALL), also known as acute lymphocytic leukemia, is a subtype of acute leukemia, a cancer of the white blood cells. Somatically acquired mutations in several genes have been identified in ALL lymphoblasts, cells in the early stages of differentiation. Germline variation in certain genes may also predispose to susceptibility to ALL (Trevino et al., 2009). Genetic Heterogeneity of Acute Lymphoblastic Leukemia A susceptibility locus for acute lymphoblastic leukemia (ALL1) has been mapped to chromosome 10q21. See also ALL2 (613067), which has been mapped to chromosome 7p12.2; and ALL3 (615545), which is caused by mutation in the PAX5 gene (167414) on chromosome 9p.
An acute lymphoblastic leukemia (current term: precursor lymphoblastic leukemia) of B-or T-cell origin which according to the FAB classification is characterized by the presence of more mature-appearing lymphoblasts.
An antiquated term that refers to acute lymphoblastic leukemia with large and irregular lymphoblasts.
A form of systemic mastocytosis (MASTOCYTOSIS, SYSTEMIC) characterized by the presence of large numbers of tissue MAST CELLS in the peripheral blood without skin lesions. It is a high-grade LEUKEMIA disease with bone marrow smear of >20% MAST CELLS, multi-organ failure and a short survival.
A rare subtype of acute myeloid leukemia evolving from primitive megakaryoblasts. []
A type of actue leukemia with features characteristic of both the myeloid and lymphoid lineages. These leukemias are for this reason are designated mixed-lineage, hybrid or biphenotypic acute leukemias.
An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.
CEBPA-associated familial acute myeloid leukemia (AML) is defined as AML in which a heterozygous germline CEBPA pathogenic variant is present in a family in which multiple individuals have AML. In contrast, sporadic CEBPA-associated AML is defined as AML in which a CEBPA pathogenic variant(s) is identified in leukemic cells but not in the non-leukemic cells. Too few individuals with CEBPA-associated familial AML have been reported to be certain about the natural history of the disease. In the majority of individuals, the age of onset of familial AML appears to be earlier than sporadic AML; disease onset has been reported in persons as young as age 1.8 years and older than age 45 years. The prognosis of CEBPA-associated familial AML appears to be favorable compared with sporadic CEBPA-associated AML. Individuals with CEBPA-associated familial AML who have been cured of their initial disease may be at greater risk of developing additional independent leukemic episodes in addition to the risk of relapse due to preexisting clones.
A clonal proliferation of myeloid cells and their precursors in the bone marrow, peripheral blood, and spleen. When the proliferating cells are immature myeloid cells and myeloblasts, it is called acute myeloid leukemia. When the proliferating myeloid cells are neutrophils, it is called chronic myelogenous leukemia.
A phase of chronic myelogenous leukemia characterized by one or more of the following: 1) Myeloblasts accounting for 10-19% of the peripheral blood white cells or of the nucleated cells in the bone marrow, 2) peripheral blood basophils at least 20%, 3) persistent thrombocytopenia that is unrelated to therapy, 4) persistent thrombocytosis despite adequate therapy, 5) increasing white blood cell count and increasing spleen size unresponsive to therapy, and/or evidence of clonal evolution. (WHO, 2001)
Chronic myeloid leukemia is a slow-growing cancer of the blood-forming tissue (bone marrow). Normal bone marrow produces red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting. In chronic myeloid leukemia, the bone marrow produces too many white blood cells. Initially, these cells function relatively normally. However, as the condition progresses, immature white blood cells called myeloblasts (or blasts) accumulate in the blood and bone marrow. The overgrowth of myeloblasts impairs development of other blood cells, leading to a shortage of red blood cells (anemia) and platelets.Chronic myeloid leukemia usually begins after age 60. Common features include excessive tiredness (fatigue), fever, and weight loss. Many affected individuals develop an enlarged spleen (splenomegaly), which can cause a feeling of fullness in the abdomen and a loss of appetite. About half of people with chronic myeloid leukemia do not initially have any signs and symptoms and are diagnosed when a blood test is performed for another reason.The condition consists of three phases: the chronic phase, the accelerated phase, and the blast phase (or blast crisis). In the chronic phase, the number of mature white blood cells is elevated, and myeloblasts account for less than 10 percent of blood cells. Signs and symptoms of the condition during this phase are typically mild or absent and worsen slowly. The chronic phase can last from months to years. In the accelerated phase, the number of myeloblasts is slightly higher, making up 10 to 29 percent of blood cells. The signs and symptoms continue to worsen. The accelerated phase usually lasts 4 to 6 months, although it is skipped in some affected individuals. In blast crisis, 30 percent or more of blood or bone marrow cells are myeloblasts. Signs and symptoms are most severe in this phase, including a massively enlarged spleen, bone pain, and weight loss. Serious infections and uncontrolled bleeding can be life-threatening.
A phase of chronic myelogenous leukemia in which the peripheral blood smear shows leukocytosis due mainly to neutrophils in different stages of maturation. Blasts usually account for less than 2% of the white blood cells counts. The platelet count is normal or increased. Thrombocytopenia is very uncommon during the chronic phase. Most patients have mild anemia. The bone marrow biopsy is hypercellular due to increased numbers of neutrophils and their precursors. Blasts usually account for fewer than 5% of the marrow cells, and more than 10% indicates transformation to the accelerated phase. Megakaryocytes are smaller than normal and have hypolobated nuclei. The spleen is enlarged due to infiltration of the cords of the red pulp by granulocytes. Most patients with chronic myelogenous leukemia are diagnosed in the chronic phase, which usually has an insidious onset and may last from several months to several years. (WHO, 2001)
A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.
A myelodysplastic/myeloproliferative neoplasm which is characterized by persistent monocytosis, absence of a Philadelphia chromosome and BCR/ABL fusion gene, fewer than 20 percent blasts in the bone marrow and blood, myelodysplasia, and absence of PDGFRA or PDGFRB rearrangement.
A rare chronic myeloproliferative neoplasm characterized by neutrophilic leukocytosis. There is no detectable Philadelphia chromosome or BCR/ABL fusion gene.
An aggressive plasma cell neoplasm characterized by the presence of neoplastic plasma cells in the peripheral blood. It is characterized by the presence of a circulating clonal plasma cell count that exceeds 2x10^9/L or is 20% of the leukocyte differential count.
An acute lymphoblastic leukemia that originates from pre-B lymphocytes. The pre-B lymphoblasts contain cytoplasmic immunoglobulin.
A mature B- or T- cell leukemia with progressive clinical course. It is characterized by the presence of medium-sized lymphocytes with visible nucleoli (prolymphocytes) in the peripheral blood, bone marrow, and spleen.
Acute promyelocytic leukemia (APL) is associated with 2 cardinal features: a granulocytic differentiation block and reciprocal and balanced translocations that always involve rearrangement of the RARA gene (180240). The most frequent translocation is t(15,17)(q21;q22), which fuses the RARA gene with the PML gene (102578) and represents more than 98% of APL (Vitoux et al., 2007).
A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.
A peripheral (mature) T-cell neoplasm linked to the human T-cell leukemia virus type 1 (HTLV-1). Adult T-cell leukemia/lymphoma is endemic in several regions of the world, in particular Japan, the Caribbean, and parts of Central Africa.
A slow-growing type of leukemia (blood cancer) in which too many lymphocytes are found in the bone marrow and/or blood. The T-cell is specified as the defective cell line.
A hematology test result that indicates the presence of an increased white blood cell count and increased neutrophil precursors resembling leukemia, in a peripheral blood smear.
Disordered formation of various types of leukocytes or an abnormal accumulation or deficiency of these cells.
A transient increase in the number of leukocytes in a body fluid.
A group of rare genetic neurodegenerative disorders that affect infants and children. These disorders are characterized by metabolic abnormalities in the development of the myelin sheaths in the white matter. Clinical signs and symptoms include developmental delays, mental retardation, dementia, seizures, loss of motor skills, and muscle weakness. Representative examples include metachromatic leukodystrophy, Krabbe disease, Canavan disease, and Alexander disease.
Krabbe disease comprises a spectrum ranging from infantile-onset disease (i.e., onset of extreme irritability, spasticity, and developmental delay before age 12 months) to later-onset disease (i.e., onset of manifestations after age 12 months and as late as the seventh decade). Although historically 85%-90% of symptomatic individuals with Krabbe disease diagnosed by enzyme activity alone have infantile-onset Krabbe disease and 10%-15% have later-onset Krabbe disease, the experience with newborn screening (NBS) suggests that the proportion of individuals with possible later-onset Krabbe disease is higher than previously thought. Infantile-onset Krabbe disease is characterized by normal development in the first few months followed by rapid severe neurologic deterioration; the average age of death is 24 months (range 8 months to 9 years). Later-onset Krabbe disease is much more variable in its presentation and disease course.
Arylsulfatase A deficiency (also known as metachromatic leukodystrophy or MLD) is characterized by three clinical subtypes: late-infantile MLD, juvenile MLD, and adult MLD. Age of onset within a family is usually similar. The disease course may be from several years in the late-infantile-onset form to decades in the juvenile- and adult-onset forms. Late-infantile MLD. Onset is before age 30 months. Typical presenting findings include weakness, hypotonia, clumsiness, frequent falls, toe walking, and dysarthria. As the disease progresses, language, cognitive, and gross and fine motor skills regress. Later signs include spasticity, pain, seizures, and compromised vision and hearing. In the final stages, children have tonic spasms, decerebrate posturing, and general unawareness of their surroundings. Juvenile MLD. Onset is between age 30 months and 16 years. Initial manifestations include decline in school performance and emergence of behavioral problems, followed by gait disturbances. Progression is similar to but slower than in the late-infantile form. Adult MLD. Onset occurs after age 16 years, sometimes not until the fourth or fifth decade. Initial signs can include problems in school or job performance, personality changes, emotional lability, or psychosis; in others, neurologic symptoms (weakness and loss of coordination progressing to spasticity and incontinence) or seizures initially predominate. Peripheral neuropathy is common. Disease course is variable – with periods of stability interspersed with periods of decline – and may extend over two to three decades. The final stage is similar to earlier-onset forms.
A disorder of the buccal mucosa resembling early leukoplakia, characterized by the presence of filmy opalescence of the mucosa in the early stages to a whitish gray cast with a coarsely wrinkled surface in the later stages, associated with intracellular edema of the spinous or malpighian layer. (Dorland, 27th ed)
A progressive demyelination within the central nervous system associated with reactivation of a latent JC virus infection.
Degeneration of white matter adjacent to the CEREBRAL VENTRICLES following cerebral hypoxia or BRAIN ISCHEMIA in neonates. The condition primarily affects white matter in the perfusion zone between superficial and deep branches of the MIDDLE CEREBRAL ARTERY. Clinical manifestations include VISION DISORDERS; CEREBRAL PALSY; PARAPLEGIA; SEIZURES; and cognitive disorders. (From Adams et al., Principles of Neurology, 6th ed, p1021; Joynt, Clinical Neurology, 1997, Ch4, pp30-1)
A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000).
A white patch or plaque on a mucous membrane that cannot be characterized clinically or pathologically as any other disease. The diagnosis of leukoplakia is one of exclusion; other conditions such as candidiasis, lichen planus, leukoedema, etc., must be ruled out before a diagnosis of leukoplakia can be made. Leukoplakia may be a premalignant condition.
A thickened white patch on the oral mucosa that cannot be rubbed off. [HPO:probinson, pmid:17944749]
A clear or white discharge from the VAGINA, consisting mainly of MUCUS.
An opioid antagonist with properties similar to those of NALOXONE; in addition it also possesses some agonist properties. It should be used cautiously; levallorphan reverses severe opioid-induced respiratory depression but may exacerbate respiratory depression such as that induced by alcohol or other non-opioid central depressants. (From Martindale, The Extra Pharmacopoeia, 30th ed, p683)
An anthelmintic drug. Co-administered with fluorouracil in the treatment of Dukes' stage C colon cancer, levamisole restores immune function through stimulating antibody formation, enhancing T-cell activity, and potentiating macrophage function. (NCI04)
A synthetic progestational hormone with actions similar to those of PROGESTERONE and about twice as potent as its racemic or (+-)-isomer (NORGESTREL). It is used for contraception, control of menstrual disorders, and treatment of endometriosis.
A condition where the heart is in the correct anatomic position but some or all of the other thoracoabdominal viscera are in the opposite lateral orientation.
An amino acid precursor of dopamine with antiparkinsonian properties. Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. When in the brain, levodopa is decarboxylated to dopamine and stimulates the dopaminergic receptors, thereby compensating for the depleted supply of endogenous dopamine seen in Parkinson's disease. To assure that adequate concentrations of levodopa reach the central nervous system, it is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, thereby diminishing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing the delivery of dopamine to the CNS.
A propionate derivative that is used to suppress coughing.
A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection.
Hypertrophy or overdevelopment of the interstitial (Leydig) cells of the testis. These cells produce testosterone.
A sex cord-stromal tumor occurring in the testis and rarely in the ovary. It is predominantly or completely composed of Leydig cells which may contain crystals of Reinke. In males it usually presents as a painless testicular enlargement and it may be associated with gynecomastia and decreased libido. The majority of the cases have a benign clinical course. Approximately 10% of the cases have a malignant clinical course and metastasize. In females it may be associated with androgenic manifestations and it follows a benign clinical course.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity.
A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND.
A chronic, recurrent, pruritic inflammatory disorder of unknown etiology that affects the skin and mucus membranes. It presents with rashes and papules that tend to resolve spontaneously. It may be associated with hepatitis C. Certain drugs that contain arsenic or bismuth are associated with reactions mimicking lichen planus.
A rare form of lichen planus that is characterized by well-demarcated, white-bluish papules or plaques with central atrophy.
A rare form of lichen planus that is characterized by the formation of vesico-bullous lesions on top of preexisting lichen planus papules or on normal skin.
A form of lichen planus that is characterized by plaques of markedly thickened skin that is often extremely pruritic and localized to the lower legs. It can result in permanent pigmentation and scarring.
A chronic inflammatory mucocutaneous disease usually affecting the female genitalia (VULVAR LICHEN SCLEROSUS) and BALANITIS XEROTICA OBLITERANS in males. It is also called white spot disease and Csillag's disease.
Thickening and hardening of the epidermis seen with exaggeration of normal skin lines.
A red or violaceous flat-topped, papular eruption that is induced by exposure to a variety of medications or environmental agents.
A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.
Coronary vasodilator with some antiarrhythmic action.
A cancer-related condition in which the gastric wall becomes thickened and rubbery (leather-bottle stomach). It is most often associated with diffuse gastric adenocarcinomas.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed)
The fixed oil obtained from the dried ripe seed of linseed, Linum usitatissimum (L. Linaceae). It is used as an emollient in liniments, pastes, and medicinal soaps, and in veterinary medicine as a laxative. It is also called flaxseed oil. (Dorland, 28th ed)
A non-neoplastic or neoplastic disorder that affects the lips. Representative examples include inflammation and carcinoma.
A benign or malignant neoplasm involving the lip.
An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3.
Errors in the metabolism of LIPIDS resulting from inborn genetic MUTATIONS that are heritable.
Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.
Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having either severe or attenuated MPS I, a distinction that influences therapeutic options. Severe MPS I. Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth decreases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life. Attenuated MPS I. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common.
A collection of heterogenous conditions resulting from defective LIPID METABOLISM and characterized by ADIPOSE TISSUE atrophy. Often there is redistribution of body fat resulting in peripheral fat wasting and central adiposity. They include generalized, localized, congenital, and acquired lipodystrophy.
A chronic systemic infection by a gram-positive bacterium, Tropheryma whippelii, mainly affecting the SMALL INTESTINE but also the JOINTS; CARDIOVASCULAR SYSTEM; and the CENTRAL NERVOUS SYSTEM. The disease is characterized by fat deposits in the INTESTINAL MUCOSA and LYMPH NODES, malabsorption, DIARRHEA with fatty stools, MALNUTRITION, and ARTHRITIS.
A naturally occurring micronutrient, synthesized in small amounts by plants and animals (including humans), with antioxidant and potential chemopreventive activities. Alpha-lipoic acid acts as a free radical scavenger and assists in repairing oxidative damage and regenerates endogenous antioxidants, including vitamins C and E and glutathione. This agent also promotes glutathione synthesis. In addition, alpha-lipoic acid exerts metal chelating capacities and functions as a cofactor in various mitochondrial enzyme complexes involved in the decarboxylation of alpha-keto acids.
Conditions characterized by abnormal lipid deposition due to disturbance in lipid metabolism, such as hereditary diseases involving lysosomal enzymes required for lipid breakdown. They are classified either by the enzyme defect or by the type of lipid involved.
Lipoid proteinosis (LP) is characterized by deposition of hyaline-like material in various tissues resulting in a hoarse voice from early infancy, vesicles and hemorrhagic crusts in the mouth and on the face and extremities, verrucous and keratotic cutaneous lesions on extensor surfaces (especially the elbows), and moniliform blepharosis (multiple beaded papules along the eyelid margins and inner canthus). Extracutaneous manifestations may include epilepsy, neuropsychiatric disorders, and spontaneous CNS hemorrhage. Males and females are affected equally. Generally, the disease course is chronic and fluctuating. Affected individuals have a normal life span unless they experience laryngeal obstruction.
A benign tumor composed of fat cells (ADIPOCYTES). It can be surrounded by a thin layer of connective tissue (encapsulated), or diffuse without the capsule.
A disorder characterized by the accumulation of encapsulated or unencapsulated tumor-like fatty tissue resembling LIPOMA.
Multiple symmetric lipomatosis (MSL) is a rare disorder characterized by the growth of uncapsulated masses of adipose tissue. It is associated with high ethanol intake and may be complicated by somatic and autonomic neuropathy and by the infiltration of the adipose tissue at the mediastinal level (summary by Enzi et al., 2002).
Sialidosis is a severe inherited disorder that affects many organs and tissues, including the nervous system. This disorder is divided into two types, which are distinguished by the age at which symptoms appear and the severity of features.Sialidosis type I, also referred to as cherry-red spot myoclonus syndrome, is the less severe form of this condition. People with type I develop signs and symptoms of sialidosis in their teens or twenties. Initially, affected individuals experience problems walking (gait disturbance) and/or a loss of sharp vision (reduced visual acuity). Individuals with sialidosis type I also experience muscle twitches (myoclonus), difficulty coordinating movements (ataxia), leg tremors, and seizures. The myoclonus worsens over time, causing difficulty sitting, standing, or walking. People with sialidosis type I eventually require wheelchair assistance. Affected individuals have progressive vision problems, including impaired color vision or night blindness. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Sialidosis type I does not affect intelligence or life expectancy.Sialidosis type II, the more severe type of the disorder, is further divided into congenital, infantile, and juvenile forms. The features of congenital sialidosis type II can develop before birth. This form of sialidosis is associated with an abnormal buildup of fluid in the abdominal cavity (ascites) or widespread swelling before birth caused by fluid accumulation (hydrops fetalis). Affected infants may also have an enlarged liver and spleen (hepatosplenomegaly), abnormal bone development (dysostosis multiplex), and distinctive facial features that are often described as ""coarse."" As a result of these serious health problems, individuals with congenital sialidosis type II usually are stillborn or die soon after birth.Infantile sialidosis type II shares some features with the congenital form, although the signs and symptoms are slightly less severe and begin within the first year of life. Features of the infantile form include hepatosplenomegaly, dysostosis multiplex, ""coarse"" facial features, short stature, and intellectual disability. As children with infantile sialidosis type II get older, they may develop myoclonus and cherry-red spots. Other signs and symptoms include hearing loss, overgrowth of the gums (gingival hyperplasia), and widely spaced teeth. Affected individuals may survive into childhood or adolescence.The juvenile form has the least severe signs and symptoms of the different forms of sialidosis type II. Features of this condition usually appear in late childhood and may include mildly ""coarse"" facial features, mild bone abnormalities, cherry-red spots, myoclonus, intellectual disability, and dark red spots on the skin (angiokeratomas). The life expectancy of individuals with juvenile sialidosis type II varies depending on the severity of symptoms.
Familial lipoprotein lipase (LPL) deficiency usually presents in childhood and is characterized by very severe hypertriglyceridemia with episodes of abdominal pain, recurrent acute pancreatitis, eruptive cutaneous xanthomata, and hepatosplenomegaly. Clearance of chylomicrons from the plasma is impaired, causing triglycerides to accumulate in plasma and the plasma to have a milky (lactescent or lipemic) appearance. Symptoms usually resolve with restriction of total dietary fat to =20 g/day.
A malignant tumor derived from primitive or embryonal lipoblastic cells. It may be composed of well-differentiated fat cells or may be dedifferentiated: myxoid (LIPOSARCOMA, MYXOID), round-celled, or pleomorphic, usually in association with a rich network of capillaries. Recurrences are common and dedifferentiated liposarcomas metastasize to the lungs or serosal surfaces. (From Dorland, 27th ed; Stedman, 25th ed)
Endogenous factors or drugs that increase the transport and metabolism of LIPIDS including the synthesis of LIPOPROTEINS by the LIVER and their uptake by extrahepatic tissues.
A bacterial infection caused by Listeria monocytogenes. It occurs in newborns, elderly, and immunocompromised patients. The bacteria are transmitted through ingestion of contaminated food. Clinical manifestations include fever, muscle pain, respiratory distress, nausea, diarrhea, neck stiffness, irritability, seizures, and lethargy.
An ergot derivative that acts as an agonist at dopamine D2 receptors (DOPAMINE AGONISTS). It may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors (SEROTONIN RECEPTOR AGONISTS).
A condition characterized by the formation of CALCULI and concretions in the hollow organs or ducts of the body. They occur most often in the gallbladder, kidney, and lower urinary tract.
An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.
A bile acid formed from chenodeoxycholate by bacterial action, usually conjugated with glycine or taurine. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as cholagogue and choleretic.
A type of cerebral palsy characterized by spasticity and hypertonia of the lower extremities bilaterally, particularly the legs, hips, and pelvis; this is the most common (70%) form of cerebral palsy.
A bacterial, parasitic, or fungal abscess that develops in the liver. It is usually the result of an abdominal infection, trauma, or surgery in the right upper quadrant. Signs and symptoms include abdominal pain, nausea, vomiting, and fever.
Single or multiple areas of PUS due to infection by any ameboid protozoa (AMEBIASIS). A common form is caused by the ingestion of ENTAMOEBA HISTOLYTICA.
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
A disorder of the liver characterized by the presence of fibrotic scar tissue instead of healthy liver tissue. This condition is attributed to excessive consumption of alcoholic beverages.
Cirrhosis of the liver caused either by destruction of the intrahepatic bile ducts (primary biliary cirrhosis) or blockage of the extrahepatic bile ducts (secondary biliary cirrhosis).
A disorder caused by damage to the liver parenchyma due to alcohol consumption. It may present with an acute onset or follow a chronic course, leading to cirrhosis.
Liver diseases caused by infections with PARASITES, such as tapeworms (CESTODA) and flukes (TREMATODA).
Extracts of liver tissue containing uncharacterized specific factors with specific activities; a soluble thermostable fraction of mammalian liver is used in the treatment of pernicious anemia.
A tumor (abnormal growth of tissue) of the liver. [HPO:probinson]
Experimentally induced tumors of the LIVER.
An alkaloid that has actions similar to NICOTINE on nicotinic cholinergic receptors but is less potent. It has been proposed for a variety of therapeutic uses including in respiratory disorders, peripheral vascular disorders, insomnia, and smoking cessation.
COL1A1/2-related osteogenesis imperfecta (OI) is characterized by fractures with minimal or absent trauma, variable dentinogenesis imperfecta (DI), and, in adult years, hearing loss. The clinical features of COL1A1/2-related OI represent a continuum ranging from perinatal lethality to individuals with severe skeletal deformities, mobility impairments, and very short stature to nearly asymptomatic individuals with a mild predisposition to fractures, normal dentition, normal stature, and normal life span. Fractures can occur in any bone, but are most common in the extremities. DI is characterized by gray or brown teeth that may appear translucent and wear down and break easily. COL1A1/2-related OI has been classified into four types (I, II, III, and IV) based on clinical presentation and radiographic findings. This classification system can be helpful in providing information about prognosis and management for a given individual. The four OI types are now referred to as follows: OI type I: classic non-deforming OI with blue sclerae. OI type II: perinatally lethal OI. OI type III: progressively deforming OI. OI type IV: common variable OI with normal sclerae.
A psychotropic IMIPRAMINE derivative that acts as a tricyclic antidepressant and possesses few anticholinergic properties. It is metabolized to DESIPRAMINE.
A parasitic infection caused by the nematode Loa loa. The vector in the transmission of this infection is the horsefly (Tabanus) or the deerfly or mango fly (Chrysops). The larvae may be seen just beneath the skin or passing through the conjunctiva. Eye lesions are not uncommon. The disease is generally mild and painless.
A nitrosourea with antineoplastic activity. Lomustine alkylates and crosslinks DNA, thereby inhibiting DNA and RNA synthesis. This agent also carbamoylates DNA and proteins, resulting in inhibition of DNA and RNA synthesis and disruption of RNA processing. Lomustine is lipophilic and crosses the blood-brain barrier. (NCI04)
Sadness resulting from being isolated or alone.
A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.
A synthetic agent chemically related to the opiates with anti-diarrheal properties. Loperamide decreases gastro-intestinal motility by effects on the circular and longitudinal muscles of the intestine. Part of its anti-diarrheal effect may be due to a reduction of gastro-intestinal secretion produced by opioid receptor binding in the intestinal mucosa. (NCI04)
A monochloroacetyl derivative of ajmaline. It is a class Ia antiarrhythmic agent that is rapidly hydrolyzed to ajmaline by plasma and tissue esterases.
A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent.
Abnormally increased curvature of the lumbar portion of the spinal column.
An acute tick-borne arbovirus infection causing meningoencephalomyelitis of sheep.
A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.
A sensation of discomfort emanating from the lower back.
A birth weight that is less than 2500 grams.
Reduced serum concentration of tri-iodothyronine caused by a variety of non-thyroidal conditions in which there is no dysfunction in the thyroid gland or the hypothalamic-pituitary axis.
Bleeding from the lower gastrointestinal tract (small intestine, large intestine, and anus).
A form of ventricular pre-excitation characterized by a short PR interval and a normal QRS complex. In this syndrome, the atrial impulse conducts via the JAMES FIBERS which connect the atrium to BUNDLE OF HIS bypassing the upper ATRIOVENTRICULAR NODE. HEART VENTRICLES are depolarized normally through the His-Purkinje system.
An antipsychotic agent used in SCHIZOPHRENIA.
The succinate salt form of loxapine, a tricyclic dibenzoxazepine antipsychotic agent with antiemetic, sedative, anticholinergic, and antiadrenergic actions. Loxapine succinate exerts its actions by blocking the dopamine receptors at postsynaptic receptor sites in the limbic system, cortical system and basal ganglia, thereby reducing the hallucinations and delusions that are associated with schizophrenia. This agent also exerts extrapyramidal side effects.
An orally available thioxanthone-based DNA intercalator and inhibitor of the DNA repair enzyme apurinic-apyrimidinic endonuclease 1 (APEX1 or APE1), with anti-schistosomal and potential antineoplastic activity. Lucanthone intercalates DNA and interferes with the activity of topoisomerases I and II during replication and transcription, thereby inhibiting the synthesis of macromolecules. In addition, this agent specifically inhibits the endonuclease activity of APE1, without affecting its redox activity, resulting in un-repaired DNA strand breaks which may induce apoptosis. Therefore, lucanthone may sensitize tumor cells to radiation and chemotherapy. Furthermore, lucanthone inhibits autophagy through the disruption of lysosomal function. The multifunctional nuclease APE1 is a key component for DNA repair; its expression is often correlated with tumor cell resistance to radio- and chemotherapy.
Severe cellulitis of the submaxillary space with secondary involvement of the sublingual and submental space. It usually results from infection in the lower molar area or from a penetrating injury to the mouth floor. (From Dorland, 27th ed)
A mass in the mammary gland, either mobile or immobile. Once the mass has reached the size of a small garden pea, it can be detected by palpation. With mammography a larger number of early breast cancers are being detected since this techniques allows detection prior to the point at which the mass can be felt. Breast masses are not always malignant. Benign fibrocystic breast disease is not uncommon. A fine needle biopsy aspiration can distinguish a cystic mass from a solid one.
A poxvirus infection of cattle characterized by the appearance of nodules on all parts of the skin.
A bacterial, fungal or parasitic abscess that develops in the lung parenchyma. Causes include aspiration pneumonia, necrotizing pneumonia, necrotizing malignant tumors, and Wegener's granulomatosis.
A non-neoplastic or neoplastic disorder affecting the lung. Representative examples of non-neoplastic disorders include chronic obstructive pulmonary disease and pneumonia. Representative examples of neoplastic disorders include benign processes (e.g., respiratory papilloma) and malignant processes (e.g., lung carcinoma and metastatic cancer to the lung).
Pulmonary diseases caused by fungal infections, usually through hematogenous spread.
Chronic obstructive pulmonary disease (COPD) is a common, complex disorder associated with substantial morbidity and mortality. COPD is defined by irreversible airflow obstruction due to chronic bronchitis, emphysema, and/or small airways disease. Airflow obstruction is typically determined by reductions in quantitative spirometric indices, including forced expiratory volume at 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (Silverman et al., 2002; Celedon et al., 2004).
Infections of the lungs with parasites, most commonly by parasitic worms (HELMINTHS).
A benign or malignant, primary or metastatic neoplasm involving the lungs. Representative examples of benign neoplasms include adenoma, papilloma, chondroma, and endobronchial lipoma. Representative examples of malignant neoplasms include carcinoma, carcinoid tumor, sarcoma, and lymphoma.
A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the NASAL MUCOSA; BUCCAL MUCOSA; and conjunctival mucosa.
Disease of skin in someone with Lupus erythematosus, though not necessarily systemic or subacute.
A chronic form of cutaneous lupus erythematosus (LUPUS ERYTHEMATOSUS, CUTANEOUS) in which the skin lesions mimic those of the systemic form but in which systemic signs are rare. It is characterized by the presence of discoid skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy. Lesions are surrounded by an elevated erythematous border. The condition typically involves the face and scalp, but widespread dissemination may occur.
A dermatologic manifestation of lupus involving erythematous, scaly patches or plaques, generally appearing on the upper back, chest, and arms, and often following sun exposure. It most often resolves without scarring.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by production of autoantibodies against nuclear, cytoplasmic, and cell surface molecules that transcend organ-specific boundaries. Tissue deposition of antibodies or immune complexes induces inflammation and subsequent injury of multiple organs and finally results in clinical manifestations of SLE, including glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures, and arthritis. Evidence strongly suggests the involvement of genetic components in SLE susceptibility (summary by Oishi et al., 2008). Genetic Heterogeneity of Systemic Lupus Erythematosus An autosomal recessive form of systemic lupus erythematosus (SLEB16; 614420) is caused by mutation in the DNASE1L3 gene (602244) on chromosome 3p14.3. See MAPPING and MOLECULAR GENETICS sections for a discussion of genetic heterogeneity of susceptibility to SLE.
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).
A condition characterized by a combination of OSTIUM SECUNDUM ATRIAL SEPTAL DEFECT and an acquired MITRAL VALVE STENOSIS.
Chemical compounds causing LUTEOLYSIS or degeneration.
A benign ovarian stromal tumor in which more than 90% of the tumor cells resemble steroid hormone-secreting cells. Crystals of Reinke are not present. It occurs in post-menopausal women and it is usually associated with estrogenic effects.
An infectious disease caused by a spirochete, BORRELIA BURGDORFERI, which is transmitted chiefly by Ixodes dammini (see IXODES) and pacificus ticks in the United States and Ixodes ricinis (see IXODES) in Europe. It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations. The disease was formerly known as Lyme arthritis and first discovered at Old Lyme, Connecticut.
Acute or chronic inflammation of one or more lymph nodes. It is usually caused by an infectious process.
Dilation of the lymphatic vessels, the basic process that may result in the formation of a lymphangioma. [MP:0004038]
Angiectasia of lymph vessels (i.e., dilatation of lymphatic vessels) in the intestines.
A lymphangioma characterized by the presence of collagen bundle formation. It has an indolent clinical course and may be associated with skin plaques.
A benign lesion composed of dilated lymphatic channels. Painless swelling is the usual clinical manifestation.
A neoplasm with perivascular epithelioid cell differentiation, often associated with tuberous sclerosis. It is characterized by the presence of smooth muscle and epithelioid cells and by the proliferation of lymphatic vessels. Sites of involvement include the lymph nodes, lung, mediastinum, and retroperitoneum.
A malignant neoplasm arising from the endothelial cells of the lymphatic vessels.
A lymphatic disease characterized by INFLAMMATION of LYMPHATIC VESSELS.
An anomaly of the lymphatic system, a network of lymphatic vessels that carry a clear fluid called lymph unidirectionally towards either the right lymphatic duct or the thoracic duct, which in turn drain into the right and left subclavian veins respectively.
Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system.
Edema due to obstruction of lymph vessels or disorders of the lymph nodes.
A cystic lesion containing lymph. It usually results from injury, gynecologic surgery, or urologic surgery.
A form of meningitis caused by LYMPHOCYTIC CHORIOMENINGITIS VIRUS. MICE and other rodents serve as the natural hosts, and infection in humans usually occurs through inhalation or ingestion of infectious particles. Clinical manifestations include an influenza-like syndrome followed by stiff neck, alterations of mentation, ATAXIA, and incontinence. Maternal infections may result in fetal malformations and injury, including neonatal HYDROCEPHALUS, aqueductal stenosis, CHORIORETINITIS, and MICROCEPHALY. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)
Excess of normal lymphocytes in the blood or in any effusion.
Infection with the organism Mycobacterium.
A group of related disorders characterized by LYMPHOCYTOSIS; HISTIOCYTOSIS; and hemophagocytosis. The two major forms are familial and reactive.
A cancer originating in lymphocytes and presenting as a solid tumor of lymhpoid cells.
A neoplasm of follicle centre B cells which has at least a partial follicular pattern. Follicular lymphomas comprise about 35% of adult non-Hodgkin lymphomas in the U.S. and 22% worldwide. Most patients have widespread disease at diagnosis. Morphologically, follicular lymphomas are classified as Grade 1, Grade 2, and Grade 3, depending on the percentage of the large lymphocytes present. The vast majority of cases (70-95%) express the BCL-2 rearrangement [t(14;18)]. Histological grade correlates with prognosis. Grades 1 and 2 follicular lymphomas are indolent and grade 3 is more aggressive (adapted from WHO, 2001).
An antiquated term that refers to a non-Hodgkin lymphoma composed of diffuse infiltrates of large, often anaplastic lymphocytes.
An antiquated term that refers to a lymphoma composed of a mixture of small and large lymphocytes.
A typer of lymphoma characterized microscopically by the absence of multinucleated Reed-Sternberg cells.
A neoplastic lymphoproliferative process characterized by an angiocentric arrangement of the tumor cells which is associated with angiodestruction. It includes lymphomatoid granulomatosis which is a lymphoproliferative lesion derived from mature B-lymphocytes and cases of extranodal NK/T-cell lymphomas of nasal type.
A reduced number of lymphocytes in the blood.
A disorder characterized by proliferation of lymphocytes at various stages of differentiation. Lymphoproliferative disorders can be neoplastic (clonal, as in lymphomas and leukemias) or reactive (polyclonal, as in infectious mononucleosis).
A synthetic progestational hormone used often in mixtures with estrogens as an oral contraceptive.
The porcine antidiuretic hormone (VASOPRESSINS). It is a cyclic nonapeptide that differs from ARG-VASOPRESSIN by one amino acid, containing a LYSINE at residue 8 instead of an ARGININE. Lys-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.
A nutritional supplement containing the biologically active L-isomer of the essential amino acid lysine, with potential anti-mucositis activity. Upon oral intake, L-lysine promotes healthy tissue function, growth and healing and improves the immune system. L-Lysine promotes calcium uptake, is essential for carnitine production and collagen formation. As collagen is essential for connective tissue maintenance, this agent may also help heal mucosal wounds. This may help decrease and prevent mucositis induced by radiation or chemotherapy.
N(6)-(2-Amino-2-carboxyethyl)-L-lysine. An unusual amino acid, not a dipeptide, which has been found in proteins of cooked foods. It is formed in food that is heated or treated with alkali. Has been implicated in nephrocytomegalia in rats.
Tissue structure disintegration and destruction due to action of endogenous or/and exogenous lytic substances which include but not limited to naturally occurring or laboratory designed proteolytic enzymes, glycosidases, detergents, pore-forming proteins, immune complexes, etc. Tissue lysis plays role in pathogenesis of a number of conditions e.g. protozoal infections, ischemic tissue injury, and autoimmune disorders. It is also used as a basis for non-surgical treatment modality to remove or minimize presence of abnormal tissue, e.g. adhesions.
A 25-kDa peptidase produced by Staphylococcus simulans which cleaves a glycine-glcyine bond unique to an inter-peptide cross-bridge of the STAPHYLOCOCCUS AUREUS cell wall. EC 3.4.24.75.
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is characterized by progressive cerebellar ataxia and variable findings including a dystonic-rigid syndrome, a parkinsonian syndrome, or a combined syndrome of dystonia and peripheral neuropathy. Neurologic findings tend to evolve as the disease progresses.
Presence of a monoclonal immunoglobulin M protein in the serum.
Macroglossia is an abnormal enlargement of the tongue. It is commonly observed with type 2 glycogen storage disease (232300), neurofibromatosis (162200), congenital hypothyroidism, and the Beckwith-Wiedemann syndrome (130650).
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.
A stromal corneal dystrophy, with autosomal recessive inheritance, that is caused by lack of or abnormal keratan sulfate.
Dominant cystoid macular dystrophy (DCMD) is a progressive retinal dystrophy characterized primarily by early-onset cystoid fluid collections in the neuroretina (summary by Saksens et al., 2015).
A neoplastic process characterized by a symmetric poorly circumscribed overgrowth of adipose tissue in the neck. It predominantly affects middle age men of Mediterranean origin.
A chronic granulomatous inflammation involving the deep dermis and the subcutaneous tissues. It is caused by fungi and actinomycetes.
The acetate salt form of mafenide, a synthetic sulfonamide analog of para-aminobenzoic acid (PABA) with topical anti-infective activity. Mafenide acetate competes with PABA for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, thereby interferes with normal folic acid metabolism. As a result, de novo synthesis of pyrimidines, which requires folate metabolites, is impeded and subsequently DNA synthesis is affected. Mafenide acetate is bacteriostatic against many gram-negative and gram-positive organisms, including Pseudomonas aeruginosa and certain strains of anaerobes.
Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis. When hemangiomata are associated, the condition is known as Maffucci syndrome. Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to osteosarcoma (Schwartz et al., 1987). Classification of the Enchondromatoses In their classification of the enchondromatoses, Spranger et al. (1978) called Ollier disease (166000) and Maffucci syndrome types I and II enchondromatosis, respectively; metachondromatosis (156250), type III; and spondyloenchondrodysplasia (607944), type IV; enchondromatosis with irregular vertebral lesions, type V; and generalized enchondromatosis, type VI. Halal and Azouz (1991) added 3 tentative categories to the 6 in the classification of Spranger et al. (1978). Pansuriya et al. (2010) suggested a new classification of enchondromatosis (multiple enchondromas).
Magnesium Chloride was used as a laxative. An alkaline earth metal, magnesium is important for many biochemical functions and reactions; for bone and muscle function, protein and fatty acid formation, activation of B vitamins, blood clotting, insulin secretion, and ATP formation. More than 300 enzymes require magnesium for catalytic action. The adult daily requirement is about 300 mg/day. Magnesium is found in many green plants, vegetables, and seeds; chlorophyll is a magnesium-centered porphyrin compound. Magnesium salts are used for magnesium deficiency supplementation. (NCI04)
A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. (Harrison's Principles of Internal Medicine, 12th ed, p1936)
A solution of magnesium hydroxide with antacid and laxative properties. Milk of magnesium exerts its antacid activity in low doses such that all hydroxide ions that enter the stomach are used to neutralize stomach acid. This agent exerts its laxative effect in higher doses so that hydroxide ions are able to move from the stomach to the intestines where they attract and retain water, thereby increasing intestinal movement (peristalsis) and inducing the urge to defecate.
Magnesium oxide (MgO). An inorganic compound that occurs in nature as the mineral periclase. In aqueous media combines quickly with water to form magnesium hydroxide. It is used as an antacid and mild laxative and has many nonmedicinal uses.
A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. (From AMA Drug Evaluations Annual, 1992, p1083)
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
An episode of depression lasting two or more weeks without an intervening episode of mania.
A syndrome resulting from the inadequate absorption of nutrients in the small intestine. Symptoms include abdominal pain, bloating, and diarrhea.
A chronic multisystem granulomatous inflammatory disease with manifestation of single or multiple soft plaques on various organs of the body. Can occur in all ages, with a mean age at diagnosis of 50 years old and a female predominance. Cases in children are rare. It is most common in immunodeficient patients with a history of diabetes, transplantation, lymphoma, steroid therapy or alcoholism. Seems to be due to an impaired response to bacterial infection.
A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.
Any of a group of infections of fowl caused by protozoa of the genera PLASMODIUM, Leucocytozoon, and Haemoproteus. The life cycles of these parasites and the disease produced bears strong resemblance to those observed in human malaria.
A condition characterized by somnolence or coma in the presence of an acute infection with PLASMODIUM FALCIPARUM (and rarely other Plasmodium species). Initial clinical manifestations include HEADACHES; SEIZURES; and alterations of mentation followed by a rapid progression to COMA. Pathologic features include cerebral capillaries filled with parasitized erythrocytes and multiple small foci of cortical and subcortical necrosis. (From Adams et al., Principles of Neurology, 6th ed, p136)
Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.
Malaria resulting from infection by Plasmodium malariae.
Malaria caused by PLASMODIUM VIVAX. This form of malaria is less severe than MALARIA, FALCIPARUM, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day.
A synthetic phosphorous compound and cholinesterase inhibitor that is strictly used as a topical pediculicide. Malathion exerts its action on the nervous system of the lice by irreversibly inhibiting the activity of cholinesterase, thereby allowing acetylcholine to accumulate at cholinergic synapses and enhancing cholinergic receptor stimulation. This eventually leads to the head lice's death.
A symptom complex associated with CARCINOID TUMOR and characterized by attacks of severe flushing of the skin, diarrheal watery stools, bronchoconstriction, sudden drops in blood pressure, edema, and ascites. The carcinoid tumors are usually located in the gastrointestinal tract and metastasize to the liver. Symptoms are caused by tumor secretion of serotonin, prostaglandins, and other biologically active substances. Cardiac manifestations constitute CARCINOID HEART DISEASE. (Dorland, 27th ed; Stedman, 25th ed)
Essential hypertension with rapid progression to severe high blood pressure, papilledema, and renal failure.
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances release calcium stores from the sarcoplasmic reticulum and may promote entry of calcium from the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience: acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some affected individuals will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high.
An epithelial or non-epithelial malignant neoplasm that arises from the liver. Representative examples include hepatocellular carcinoma, intrahepatic cholangiocarcinoma, lymphoma, and sarcoma.
Abnormal growth of cells comprising the retina with malignant characteristics.
A primary or metastatic malignant neoplasm involving the stomach.
A condition characterized by mucosal tears at the ESOPHAGOGASTRIC JUNCTION, sometimes with HEMATEMESIS. Typically it is caused by forceful bouts of retching or VOMITING.
An inherited or acquired dental abnormality characterized by improper alignment of the teeth.
Any anatomical misplacement of the heart and cardiac apex such that the organ occupies an unusual location within the body.
A dextrodisaccharide from malt and starch. It is used as a sweetening agent and fermentable intermediate in brewing. (Grant & Hackh's Chemical Dictionary, 5th ed)
Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.
Polysaccharides consisting of mannose units.
A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity.
A nitrogen mustard derivative that cross-links with DNA, causing inhibition of DNA synthesis. It may be used to treat certain cancers, but may cause a higher incidence of leukemia and a dose-related incidence of lung tumors in animals. (NCI)
A hexose or fermentable monosaccharide and isomer of glucose from manna, the ash Fraxinus ornus and related plants. (From Grant & Hackh's Chemical Dictionary, 5th ed & Random House Unabridged Dictionary, 2d ed)
Alpha-mannosidosis encompasses a continuum of clinical findings from mild to severe. Three major clinical subtypes have been suggested: A mild form recognized after age ten years with absence of skeletal abnormalities, myopathy, and slow progression (type 1). A moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression (type 2). A severe form manifested as prenatal loss or early death from progressive central nervous system involvement or infection (type 3). Individuals with a milder phenotype have mild-to-moderate intellectual disability, impaired hearing, characteristic coarse features, clinical or radiographic skeletal abnormalities, immunodeficiency, and primary central nervous system disease – mainly cerebellar involvement causing ataxia. Periods of psychiatric symptoms are common. Associated medical problems can include corneal opacities, hepatosplenomegaly, aseptic destructive arthritis, and metabolic myopathy. Alpha-mannosidosis is insidiously progressive; some individuals may live into the sixth decade.
A parasitic infection caused by the nematode Mansonella. Signs and symptoms include pruritus, headache, fever, arthralgias, and eosinophilia.
Maple syrup urine disease (MSUD) is classified as classic or intermediate. Twelve hours after birth, untreated neonates with classic MSUD have a maple syrup odor in cerumen; by 12-24 hours, elevated plasma concentrations of branched-chain amino acids (BCAAs) (leucine, isoleucine, and valine) and allo-isoleucine, as well as a generalized disturbance of plasma amino acid concentration ratios; by age two to three days, ketonuria, irritability, and poor feeding; by age four to five days, deepening encephalopathy manifesting as lethargy, intermittent apnea, opisthotonus, and stereotyped movements such as ""fencing"" and ""bicycling."" By age seven to ten days, coma and central respiratory failure may supervene. Individuals with intermediate MSUD have partial BCKAD enzyme deficiency that only manifests intermittently or responds to dietary thiamine therapy; these individuals can experience severe metabolic intoxication and encephalopathy during sufficient catabolic stress.
A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use.
A viral infectious disorder caused by Marburg virus. Signs and symptoms include fever, headache, myalgias, chest and abdominal pain, jaundice, liver failure, massive hemorrhaging, and multiple organ failure.
Paroxysmal nocturnal hemoglobinuria is an acquired disorder that leads to the premature death and impaired production of blood cells. The disorder affects red blood cells (erythrocytes), which carry oxygen; white blood cells (leukocytes), which protect the body from infection; and platelets (thrombocytes), which are involved in blood clotting. Paroxysmal nocturnal hemoglobinuria affects both sexes equally, and can occur at any age, although it is most often diagnosed in young adulthood.People with paroxysmal nocturnal hemoglobinuria have sudden, recurring episodes of symptoms (paroxysmal symptoms), which may be triggered by stresses on the body, such as infections or physical exertion. During these episodes, red blood cells are prematurely destroyed (hemolysis). Affected individuals may pass dark-colored urine due to the presence of hemoglobin, the oxygen-carrying protein in blood. The abnormal presence of hemoglobin in the urine is called hemoglobinuria. In many, but not all cases, hemoglobinuria is most noticeable in the morning, upon passing urine that has accumulated in the bladder during the night (nocturnal).The premature destruction of red blood cells results in a deficiency of these cells in the blood (hemolytic anemia), which can cause signs and symptoms such as fatigue, weakness, abnormally pale skin (pallor), shortness of breath, and an increased heart rate. People with paroxysmal nocturnal hemoglobinuria may also be prone to infections due to a deficiency of white blood cells.Abnormal platelets associated with paroxysmal nocturnal hemoglobinuria can cause problems in the blood clotting process. As a result, people with this disorder may experience abnormal blood clotting (thrombosis), especially in large abdominal veins; or, less often, episodes of severe bleeding (hemorrhage).Individuals with paroxysmal nocturnal hemoglobinuria are at increased risk of developing cancer in blood-forming cells (leukemia).In some cases, people who have been treated for another blood disease called aplastic anemia may develop paroxysmal nocturnal hemoglobinuria.
A viral infection in chickens caused by the herpes virus. It is characterized by tissue lymphocytic infiltration, limb paralysis and development of tumors.
Marfan syndrome, a systemic disorder of connective tissue with a high degree of clinical variability, comprises a broad phenotypic continuum ranging from mild (features of Marfan syndrome in one or a few systems) to severe and rapidly progressive neonatal multiorgan disease. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. Ocular findings include myopia (the most common ocular feature); ectopia lentis (seen in approximately 60% of affected individuals); and an increased risk for retinal detachment, glaucoma, and early cataracts. Skeletal system manifestations include bone overgrowth and joint laxity; disproportionately long extremities for the size of the trunk (dolichostenomelia); overgrowth of the ribs that can push the sternum in (pectus excavatum) or out (pectus carinatum); and scoliosis that ranges from mild to severe and progressive. The major morbidity and early mortality in the Marfan syndrome relate to the cardiovascular system and include dilatation of the aorta at the level of the sinuses of Valsalva (predisposing to aortic tear and rupture), mitral valve prolapse with or without regurgitation, tricuspid valve prolapse, and enlargement of the proximal pulmonary artery. Severe and prolonged regurgitation of the mitral and/or aortic valve can predispose to left ventricular dysfunction and occasionally heart failure. With proper management, the life expectancy of someone with Marfan syndrome approximates that of the general population.
A well-known complication of GASTROENTEROSTOMY. These ulcers occur at the gastrojejunal anastomosis, mostly on the jejunal side.
Any part of, or extract from, the female hemp plant Cannabis sativa. Marijuana contains cannabinoids, substances with hallucinogenic, psychoactive, and addictive properties. This agent has potential use for treating cancer pain and cachexia. (NCI04)
Use of marijuana associated with abnormal psychological, social, and or occupational functioning.
Marinesco-Sjögren syndrome (MSS) is characterized by cerebellar ataxia with cerebellar atrophy, dysarthria, nystagmus, early-onset (not necessarily congenital) cataracts, myopathy, muscle weakness, and hypotonia. Additional features may include psychomotor delay, hypergonadotropic hypogonadism, short stature, and various skeletal abnormalities. Children with MSS usually present with muscular hypotonia in early infancy; distal and proximal muscular weakness is noticed during the first decade of life. Later, cerebellar findings of truncal ataxia, dysdiadochokinesia, nystagmus, and dysarthria become apparent. Motor function worsens progressively for some years, then stabilizes at an unpredictable age and degree of severity. Cataracts can develop rapidly and typically require lens extraction in the first decade of life. Although many adults have severe disabilities, life span in MSS appears to be near normal.
A demographic parameter indicating a person's current conjugal status.
The social institution involving legal and/or religious sanction whereby individuals are joined together.
Pleasure derived from being physically or psychologically abused, whether inflicted by oneself or by others. Masochism includes sexual masochism.
INFLAMMATION of the BREAST, or MAMMARY GLAND.
A localized tumor composed of sheets of mast cells without atypia. It includes the cutaneous mastocytoma which involves the dermis and subcutaneous tissue, and the extracutaneous mastocytoma. Most cases of extracutaneous mastocytoma have been reported in the lung.
Mastocytosis, or mast cell disease, is a heterogeneous group of clinical disorders characterized by the abnormal accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. Mastocytosis usually appears in infancy or early adulthood. In most pediatric cases, the disease is limited to the skin, but it can be associated with systemic symptoms due to the release of mediators from mast cells, even when there is no systemic infiltration. It usually has a good prognosis, with substantial improvement or spontaneous resolution before puberty. In rare cases, the disease may remain active through adolescence as a systemic adult mastocytosis. Cutaneous mastocytosis is characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed the 'Darier sign.' In contrast to childhood-onset mastocytosis, adult-onset mastocytosis often persists for the lifetime of the patient and is also more likely to be a severe and systemic disease involving numerous organs. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. Adult-onset mastocytosis can also lead to the rare mast cell leukemia, which carries a high risk of mortality (summary by Bodemer et al., 2010 and Kambe et al., 2010).
A form of cutaneous mastocytosis that is characterized by the large fluid-filled lesions.
A variant of cutaneous mastocytosis which is seen almost exclusively in children. (WHO, 2001) -- 2003
Pain in the breast generally classified as cyclical (associated with menstrual periods), or noncyclical, i.e. originating from the breast or nearby muscles or joints, ranging from minor discomfort to severely incapacitating.
Inflammation of the honeycomb-like MASTOID BONE in the skull just behind the ear. It is usually a complication of OTITIS MEDIA.
Materials or substances used in the composition of traditional medical remedies. The use of this term in MeSH was formerly restricted to historical articles or those concerned with traditional medicine, but it can also refer to homeopathic remedies. Nosodes are specific types of homeopathic remedies prepared from causal agents or disease products.
Cancer or tumors of the MAXILLA or upper jaw.
A benign or malignant neoplasm that affects the maxillary sinus. Representative examples of benign neoplasms include Schneiderian papilloma and salivary gland-type adenoma. Representative examples of malignant neoplasms include carcinoma and lymphoma.
An acute or chronic inflammatory process affecting the mucous membrane of the maxillary sinus.
Measure of the maximum amount of air that can be breathed in and blown out over a sustained interval such as 15 or 20 seconds. Common abbreviations are MVV and MBC.
An ansamycin antibiotic originally isolated from the Ethiopian shrub Maytenus serrata. Maytansine binds to tubulin at the rhizoxin binding site, thereby inhibiting microtubule assembly, inducing microtubule disassembly, and disrupting mitosis. Maytansine exhibits cytotoxicity against many tumor cell lines and may inhibit tumor growth in vivo. (NCI04)
Tricyclic anorexigenic agent unrelated to and less toxic than AMPHETAMINE, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter.
A highly contagious infectious disease caused by MORBILLIVIRUS, common among children but also seen in the nonimmune of any age, in which the virus enters the respiratory tract via droplet nuclei and multiplies in the epithelial cells, spreading throughout the MONONUCLEAR PHAGOCYTE SYSTEM.
A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had measles or been immunized with live measles vaccine and have no serum antibodies against measles. Children are usually immunized with measles-mumps-rubella combination vaccine. (From Dorland, 28th ed)
A benzimidazole that acts by interfering with CARBOHYDRATE METABOLISM and inhibiting polymerization of MICROTUBULES.
A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.
A biologic alkylating agent that exerts its cytotoxic effects by forming DNA ADDUCTS and DNA interstrand crosslinks, thereby inhibiting rapidly proliferating cells. The hydrochloride is an antineoplastic agent used to treat HODGKIN DISEASE and LYMPHOMA.
A congenital abnormality characterized by the outpouching or sac formation in the ILEUM. It is a remnant of the embryonic YOLK SAC in which the VITELLINE DUCT failed to close.
A histamine H1 antagonist used in the treatment of motion sickness, vertigo, and nausea during pregnancy and radiation sickness.
The sodium salt form of meclofenamate, an anthranilic acid and non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic and analgesic activities. Meclofenamate sodium inhibits the activity of the enzymes cyclo-oxygenase I and II, resulting in decreased formation of precursors of prostaglandins and thromboxanes. The resulting decrease in prostaglandin synthesis, by prostaglandin synthase, is responsible for the therapeutic effects of meclofenamate sodium. Meclofenamate sodium also causes a decrease in the formation of thromboxane A2 synthesis, by thromboxane synthase, thereby inhibiting platelet aggregation.
A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.
A condition caused by inhalation of MECONIUM into the LUNG of FETUS or NEWBORN, usually due to vigorous respiratory movements during difficult PARTURITION or respiratory system abnormalities. Meconium aspirate may block small airways leading to difficulties in PULMONARY GAS EXCHANGE and ASPIRATION PNEUMONIA.
A benzodiazepine derivative used in the treatment of anxiety. It has sedative, muscle relaxant, and anticonvulsant properties. One of its metabolites is DIAZEPAM and one of its excretion products is OXAZEPAM.
A fluid-filled, epithelium-lined cyst located in the mediastinum.
A non-neoplastic or neoplastic disorder that affects the structures of the mediastinum. Representative examples include mediastinitis, mediastinal lipoma, mediastinal schwannoma, thymoma, and mediastinal lymphoma.
Presence of air in the mediastinal tissues due to leakage of air from the tracheobronchial tree, usually as a result of trauma.
A benign or malignant neoplasm that affects the structures of the mediastinum. Representative examples include mediastinal lipoma, mediastinal schwannoma, thymoma, and mediastinal lymphoma.
An inflammatory process affecting the mediastinum.
A semisynthetic digitalis glycoside with the general properties of DIGOXIN but more rapid onset of action. Its cardiotonic action is prolonged by its demethylation to DIGOXIN in the liver. It has been used in the treatment of congestive heart failure (HEART FAILURE).
6,17-Dimethylpregna-4,6-diene-3,20-dione. A synthetic progestational hormone with actions similar to those of progesterone. It is used in the treatment of menstrual irregularities and has also been employed in the treatment of prostatic hypertrophy and endometrial carcinoma.
(6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator.
Medulloblastoma is the most common brain tumor in children. It accounts for 16% of all pediatric brain tumors, and 40% of all cerebellar tumors in childhood are medulloblastoma. Medulloblastoma occurs bimodally, with peak incidences between 3 and 4 years and 8 and 9 years of age. Approximately 10 to 15% of medulloblastomas are diagnosed in infancy. Medulloblastoma accounts for less than 1% of central nervous system (CNS) tumors in adults, with highest incidence in adults 20 to 34 years of age. In 1 to 2% of patients, medulloblastoma is associated with Gorlin syndrome (109400), a nevoid basal carcinoma syndrome. Medulloblastoma also occurs in up to 40% of patients with Turcot syndrome (276300). Medulloblastoma is thought to arise from neural stem cell precursors in the granular cell layer of the cerebellum. Standard treatment includes surgery, chemotherapy, and, depending on the age of the patient, radiation therapy (Crawford et al., 2007).
A non-steroidal anti-inflammatory agent with analgesic, anti-inflammatory, and antipyretic properties. It is an inhibitor of cyclooxygenase.
A phospholipid-interacting antimalarial drug (ANTIMALARIALS). It is very effective against PLASMODIUM FALCIPARUM with very few side effects.
A benzene-sulfonamide-furan. It is used as a diuretic that affects the concentrating ability of the KIDNEY, increases SODIUM CHLORIDE excretion, but may not spare POTASSIUM. It inhibits CARBONIC ANHYDRASES and may increase the blood URIC ACID level.
Bacteriocins elaborated by mutant strains of Bacillus megaterium. They are protein or protein-lipopolysaccharide complexes lethal to other strains of the same species.
An abnormal dilation of the colon not due to obstruction.
An acute form of MEGACOLON, severe pathological dilatation of the COLON. It is associated with clinical conditions such as ULCERATIVE COLITIS; CROHN DISEASE; AMEBIC DYSENTERY; or CLOSTRIDIUM ENTEROCOLITIS.
An abnormal dilation of the esophagus not due to obstruction.
17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer.
1-Deoxy-1-(methylamino)-D-glucitol. A derivative of sorbitol in which the hydroxyl group in position 1 is replaced by a methylamino group. Often used in conjunction with iodinated organic compounds as contrast medium.
A syndrome characterized by orofacial DYSTONIA; including BLEPHAROSPASM; forceful jaw opening; lip retraction; platysma muscle spasm; and tongue protrusion. It primarily affects older adults, with an incidence peak in the seventh decade of life. (From Adams et al., Principles of Neurology, 6th ed, p108)
A rare syndrome affecting females. It is characterized by pleural effusion, ascites and non-malignant ovarian neoplasm. This syndrome usually follows a benign course. Prognosis is favorable following surgical resection of the ovarian mass.
A subtype of depression characterized by the inability to find pleasure in positive things combined with physical agitation, insomnia, or decreased appetite.
Melanoma is a type of skin cancer that begins in pigment-producing cells called melanocytes. This cancer typically occurs in areas that are only occasionally sun-exposed; tumors are most commonly found on the back in men and on the legs in women. Melanoma usually occurs on the skin (cutaneous melanoma), but in about 5 percent of cases it develops in melanocytes in other tissues, including the eyes (uveal melanoma) or mucous membranes that line the body's cavities, such as the moist lining of the mouth (mucosal melanoma). Melanoma can develop at any age, but it most frequently occurs in people in their fifties to seventies and is becoming more common in teenagers and young adults.Melanoma may develop from an existing mole or other normal skin growth that becomes cancerous (malignant); however, many melanomas are new growths. Melanomas often have ragged edges and an irregular shape. They can range from a few millimeters to several centimeters across. They can also be a variety of colors: brown, black, red, pink, blue, or white.Most melanomas affect only the outermost layer of skin (the epidermis). If a melanoma becomes thicker and involves multiple layers of skin, it can spread to other parts of the body (metastasize).A large number of moles or other pigmented skin growths on the body, generally more than 25, is associated with an increased risk of developing melanoma. Melanoma is also a common feature of genetic syndromes affecting the skin such as xeroderma pigmentosum. Additionally, individuals who have previously had melanoma are nearly nine times more likely than the general population to develop melanoma again. It is estimated that about 90 percent of individuals with melanoma survive at least 5 years after being diagnosed.
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.
Disorders of increased melanin pigmentation that develop without preceding inflammatory disease.
A congenital lesionof the sclera characterized by unilateral patchy but extensive slate-gray or bluish discoloration of the sclera . The conjunctiva are spared.
Arsenical used in trypanosomiases. It may cause fatal encephalopathy and other undesirable side effects.
Symmetrical patches of tan or brown discoloration on the skin of the face that darken with sun exposure.
A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant.
Mal de Meleda is a rare skin disorder that begins in early infancy. Affected individuals have a condition known as palmoplantar keratoderma, in which the skin of the palms of the hands and soles of the feet becomes thick, hard, and callused. In mal de Meleda, the thickened skin is also found on the back of the hands and feet and on the wrists and ankles. In addition, affected individuals may have rough, thick pads on the joints of the fingers and toes and on the elbows and knees. Some people with mal de Meleda have recurrent fungal infections in the thickened skin, which can lead to a strong odor. Other features of this disorder can include short fingers and toes (brachydactyly), nail abnormalities, red skin around the mouth, and excessive sweating (hyperhidrosis).
Abnormally dark tarry feces containing blood, usually from gastrointestinal bleeding.
A 6-methyl PROGESTERONE acetate with reported glucocorticoid activity and effect on ESTRUS.
A disease of humans and animals that resembles GLANDERS. It is caused by BURKHOLDERIA PSEUDOMALLEI and may range from a dormant infection to a condition that causes multiple abscesses, pneumonia, and bacteremia.
A rare syndrome characterized by recurrent facial nerve paralysis, edema of the lips and face, and furrowed tongue.
The otopalatodigital (OPD) spectrum disorders, characterized primarily by skeletal dysplasia, include the following: Otopalatodigital syndrome type I (OPD1). Otopalatodigital syndrome type II (OPD2). Frontometaphyseal dysplasia (FMD). Melnick-Needles syndrome (MNS). Terminal osseous dysplasia with pigmentary skin defects (TODPD). In OPD1, most manifestations are present at birth; females can present with severity similar to affected males, although some have only mild manifestations. In OPD2, females are less severely affected than related affected males. Most males with OPD2 die during the first year of life, usually from thoracic hypoplasia resulting in pulmonary insufficiency. Males who live beyond the first year of life are usually developmentally delayed and require respiratory support and assistance with feeding. In FMD, females are less severely affected than related affected males. Males do not experience progression of skeletal dysplasia but may have joint contractures and hand and foot malformations. Progressive scoliosis is observed in both affected males and females. In MNS, wide phenotypic variability is observed; some individuals are diagnosed in adulthood, while others require respiratory support and have reduced longevity. Prenatal lethality is most common in males with MNS. TODPD is a female limited condition, characterized by terminal skeletal dysplasia, pigmentary defects of the skin, and recurrent digital fibromata.
A form of osteosclerosis extending in a linear track mainly through one of the long bones of the upper and lower limbs.
A phenylalanine derivative of nitrogen mustard with antineoplastic activity. Melphalan alkylates DNA at the N7 position of guanine and induces DNA inter-strand cross-linkages, resulting in the inhibition of DNA and RNA synthesis and cytotoxicity against both dividing and non-dividing tumor cells.
AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.
The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature.
The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.
Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.
Multiple endocrine neoplasia type 1 (MEN1) syndrome includes varying combinations of more than 20 endocrine and non-endocrine tumors. Endocrine tumors become evident either by overproduction of hormones by the tumor or by growth of the tumor itself. Parathyroid tumors are the main MEN1-associated endocrinopathy; onset in 90% of individuals is between ages 20 and 25 years with hypercalcemia evident by age 50 years; hypercalcemia causes lethargy, depression, confusion, anorexia, constipation, nausea, vomiting, diuresis, dehydration, hypercalciuria, kidney stones, increased bone resorption/fracture risk, hypertension, and shortened QT interval. Pituitary tumors include prolactinoma (the most common), which manifests as oligomenorrhea/amenorrhea and galactorrhea in females and sexual dysfunction in males. Well-differentiated endocrine tumors of the gastro-entero-pancreatic (GEP) tract can manifest as Zollinger-Ellison syndrome (gastrinoma); hypoglycemia (insulinoma); hyperglycemia, anorexia, glossitis, anemia, diarrhea, venous thrombosis, and skin rash (glucagonoma); and watery diarrhea, hypokalemia, and achlorhydria syndrome (vasoactive intestinal peptide [VIP]-secreting tumor). Carcinoid tumors are non-hormone-secreting and can manifest as a large mass after age 50 years. Adrenocortical tumors can be associated with primary hypercortisolism or hyperaldosteronism. Non-endocrine tumors include facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas.
Multiple endocrine neoplasia type 2 (MEN 2) is classified into three subtypes: MEN 2A, FMTC (familial medullary thyroid carcinoma), and MEN 2B. All three subtypes involve high risk for development of medullary carcinoma of the thyroid (MTC); MEN 2A and MEN 2B have an increased risk for pheochromocytoma; MEN 2A has an increased risk for parathyroid adenoma or hyperplasia. Additional features in MEN 2B include mucosal neuromas of the lips and tongue, distinctive facies with enlarged lips, ganglioneuromatosis of the gastrointestinal tract, and a ""marfanoid"" habitus. MTC typically occurs in early childhood in MEN 2B, early adulthood in MEN 2A, and middle age in FMTC.
A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo.
Meniere disease is a chronic illness characterized by intermittent episodes of vertigo lasting from minutes to hours, with fluctuating sensorineural hearing loss, tinnitus, and aural pressure (Sajjadi and Paparella, 2008).
A benign or malignant neoplasm that affects the meninges. The majority of the neoplasms arise from meningothelial cells and are called meningiomas. Non-meningothelial cell neoplasms include mesenchymal, non-meningothelial tumors, hemangiopericytomas, and melanocytic lesions.
A generally slow growing tumor attached to the dura mater. It is composed of neoplastic meningothelial (arachnoidal) cells. It typically occurs in adults, often women and it has a wide range of histopathological appearances. Of the various subtypes, meningothelial, fibrous and transitional meningiomas are the most common. Most meningiomas are WHO grade I tumors, and some are WHO grade II or III tumors. Most subtypes share a common clinical behavior, although some subtypes are more likely to recur and follow a more aggressive clinical course. (Adapted from WHO)
A condition characterized by neck stiffness, headache, and other symptoms suggestive of meningeal irritation, but without actual inflammation of the meninges (MENINGITIS). Spinal fluid pressure may be elevated but spinal fluid is normal. (DeJong, The Neurologic Examination, 4th ed, p673)
A disorder characterized by acute inflammation of the meninges of the brain and/or spinal cord.
A syndrome characterized by headache, neck stiffness, low grade fever, and CSF lymphocytic pleocytosis in the absence of an acute bacterial pathogen. Viral meningitis is the most frequent cause although MYCOPLASMA INFECTIONS; RICKETTSIA INFECTIONS; diagnostic or therapeutic procedures; NEOPLASTIC PROCESSES; septic perimeningeal foci; and other conditions may result in this syndrome. (From Adams et al., Principles of Neurology, 6th ed, p745)
Infections of the nervous system caused by bacteria of the genus HAEMOPHILUS, and marked by prominent inflammation of the MENINGES. HAEMOPHILUS INFLUENZAE TYPE B is the most common causative organism. The condition primarily affects children under 6 years of age but may occur in adults.
Inflammation of the meninges caused by LISTERIA MONOCYTOGENES infection, usually occurring in individuals under the age of 3 years or over the age of 50 years. It may occur at any age in individuals with IMMUNOLOGIC DEFICIENCY SYNDROMES. Clinical manifestations include FEVER, altered mentation, HEADACHE, meningeal signs, focal neurologic signs, and SEIZURES. (From Medicine 1998 Sep;77(5):313-36)
A fulminant infection of the meninges and subarachnoid fluid by the bacterium NEISSERIA MENINGITIDIS, producing diffuse inflammation and peri-meningeal venous thromboses. Clinical manifestations include FEVER, nuchal rigidity, SEIZURES, severe HEADACHE, petechial rash, stupor, focal neurologic deficits, HYDROCEPHALUS, and COMA. The organism is usually transmitted via nasopharyngeal secretions and is a leading cause of meningitis in children and young adults. Organisms from Neisseria meningitidis serogroups A, B, C, Y, and W-135 have been reported to cause meningitis. (From Adams et al., Principles of Neurology, 6th ed, pp689-701; Curr Opin Pediatr 1998 Feb;10(1):13-8)
An acute purulent infection of the meninges and subarachnoid space caused by Streptococcus pneumoniae, most prevalent in children and adults over the age of 60. This illness may be associated with OTITIS MEDIA; MASTOIDITIS; SINUSITIS; RESPIRATORY TRACT INFECTIONS; sickle cell disease (ANEMIA, SICKLE CELL); skull fractures; and other disorders. Clinical manifestations include FEVER; HEADACHE; neck stiffness; and somnolence followed by SEIZURES; focal neurologic deficits (notably DEAFNESS); and COMA. (From Miller et al., Merritt's Textbook of Neurology, 9th ed, p111)
Inflammation of the membranes surrounding the brain and spinal cord due to a viral infection.
Protrusion of the meninges through a defect of the vertebral column.
Infections with bacteria of the species NEISSERIA MENINGITIDIS.
An inflammatory process involving the brain (ENCEPHALITIS) and meninges (MENINGITIS), most often produced by pathogenic organisms which invade the central nervous system, and occasionally by toxins, autoimmune disorders, and other conditions.
Myelocystocele is characterized by a large, ependyma-lined, cystic dilation of the caudal end of the central canal of the spinal cord; it projects dorsally through a lamina defect, with overlying varying amounts of lipomatous subcutaneous tissue. Myelocystoceles are associated with a tethered cord and meningocele, which communicates with the spinal subarachnoid space, but not with the central canal cyst.
A grouping of variable physical, vasomotor and psychological symptoms in climacteric females. Physical symptoms include: cessation of menses, headaches, fatigue, weight gain and vaginal dryness. Vasomotor symptoms typically include: palpitations, hot flashes and night sweats. Psychological symptoms may include: decrease in libido, emotional lability, difficulty concentrating and insomnia.
Amenorrhea due to loss of ovarian function before the age of 40. Primary ovarian inssuficiency (POI) is a state of female hypergonadotropic hypogonadism. It can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea.
Excessive uterine bleeding during MENSTRUATION.
A mixture of gonadotropins purified from the urine of postmenopausal women, which contains high levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), with potential use as a treatment for infertility. Menotropins may also contain or be administered sequentially or simultaneously with human chorionic gonadotropin (hCG). Gonadotropins stimulate discrete cellular components of the gonads and improve ovulation, follicular growth and maturation, or spermatogenesis.
A category of conditions related to menses.
Chemical compounds that induce menstruation either through direct action on the reproductive organs or through indirect action by relieving another condition of which amenorrhea is a secondary result. (From Dorland, 27th ed)
A developmental disorder characterized by less than average intelligence and significant limitations in adaptive behavior with onset before the age of 18.
Reversible mental retardation due to environmental and/or social factors with no organic etiological component.
An alcohol produced from mint oils or prepared synthetically.
A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration.
A centrally acting muscle relaxant with a short duration of action.
A sympathomimetic agent with specificity for alpha-1 adrenergic receptors. It is used to maintain BLOOD PRESSURE in hypotensive states such as following SPINAL ANESTHESIA.
A heterocyclic organic compound with anticonvulsant property. Although the mechanism of action is not well established, mephenytoin potentially promotes sodium efflux from neurons in motor cortex, and stabilizes the threshold against hyperexcitability caused by excessive stimulation. Thus this agent reduces the membrane sodium gradient and prevents cortical seizure signal spreading. It may cause blood dyscrasias, therefore, this agent was only used after other less toxic anticonvulsants had failed.
A barbiturate that is metabolized to PHENOBARBITAL. It has been used for similar purposes, especially in EPILEPSY, but there is no evidence mephobarbital offers any advantage over PHENOBARBITAL.
A local anesthetic that is chemically related to BUPIVACAINE but pharmacologically related to LIDOCAINE. It is indicated for infiltration, nerve block, and epidural anesthesia. Mepivacaine is effective topically only in large doses and therefore should not be used by this route. (From AMA Drug Evaluations, 1994, p168)
A carbamate derivate with hypnotic, anti-anxiety, sedative, anticonvulsant and some indirect muscle relaxant properties. Although the exact mechanism of meprobamate is largely unknown, it appears to act as a depressant at multiple sites in the central nervous system, mostly likely through the GABAergic neurotransmitter system, including the thalamus and limbic system.
A narcotic antagonist with analgesic properties. It is used for the control of moderate to severe pain.
A once-popular mercury containing topical antiseptic.
An acylated sulfhydryl-containing derivative of glycine with reducing and complexing properties. Tiopronin breaks the disulphide bond of cystine and binds the sulfhydryl group of the resultant cysteine monomers to form a soluble tiopronin-cysteine-mixed disulfide, which is more water-soluble than cystine and is readily excreted. This leads to a reduction in urinary cystine concentration and subsequently reduces cystine stone formation.
Mercury chloride (HgCl2). A highly toxic compound that volatizes slightly at ordinary temperature and appreciably at 100 degrees C. It is corrosive to mucous membranes and used as a topical antiseptic and disinfectant.
The isomeric form of melphalan, with alkylating activity. Sarcolysin crosslinks DNA, thereby causing an inhibition in DNA replication and eventually a reduction in cellular proliferation.
A term describing a soft tissue tumor which consists of two or more mesenchymal lines of differentiation, excluding a fibroblastic line of differentiation.
A closed fluid filled sac originating from the mesentary.
INFLAMMATION of LYMPH NODES in the MESENTERY.
Inflammation of the ADIPOSE TISSUE in the MESENTERY, a form of peritoneal panniculitis, It is characterized by the presence of MULTINUCLEATED GIANT CELLS and lipid-laden MACROPHAGES in the mesentery.
Obstruction of the flow in the SPLANCHNIC CIRCULATION by ATHEROSCLEROSIS; EMBOLISM; THROMBOSIS; STENOSIS; TRAUMA; and compression or intrinsic pressure from adjacent tumors. Rare causes are drugs, intestinal parasites, and vascular immunoinflammatory diseases such as PERIARTERITIS NODOSA and THROMBOANGIITIS OBLITERANS. (From Juergens et al., Peripheral Vascular Diseases, 5th ed, pp295-6)
Migration of the teeth toward the midline or forward in the DENTAL ARCH. (From Boucher's Clinical Dental Terminology, 4th ed)
An adenocarcinoma of the cervix or the vagina arising from mesonephric remnants.
A phenothiazine antipsychotic with effects similar to CHLORPROMAZINE.
A tumor derived from mesothelial tissue (peritoneum, pleura, pericardium). It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. (Dorland, 27th ed)
17 beta-Hydroxy-1 alpha-methyl-5 alpha-androstan-3-one. A synthetic steroid with anabolic and androgenic activities.
A semisynthetic estrogen. Metabolized by the liver to ethynyl estradiol, mestranol serves as the estrogen component in several combination oral contraceptives. (NCI04)
The conversion of an exogenous substance by a biological system resulting in the production on an active metabolite.
A congenital (due to inherited enzyme abnormality) or acquired (due to failure of a metabolic important organ) disorder resulting from an abnormal metabolic process.
A group of disorders present at birth that involve genetic defects leading to disturbances in carbohydrate, lipid, lysosomal storage or amino acid metabolism in the body.
An infection that is most commonly caused by the intestinal fluke Metagonimus yokogawai, which is most commonly found in the Far East, and which is transmitted via consumption of contaminated raw or undercooked fish. Symptoms typically range from asymptomatic to intermittent abdominal pain and diarrhea, with occasional ectopic infection.
Dysfunctions in the metabolism of metals resulting from inborn genetic mutations that are inherited or acquired in utero.
Porphyrins which are combined with a metal ion. The metal is bound equally to all four nitrogen atoms of the pyrrole rings. They possess characteristic absorption spectra which can be utilized for identification or quantitative estimation of porphyrins and porphyrin-bound compounds.
A condition in which there is a change of one adult cell type to another similar adult cell type.
A morphologic finding indicating the transformation of glandular or transitional epithelial cells to, usually, mature squamous epithelial cells. Representative examples include squamous metaplasia of bronchial epithelium, cervix, urinary bladder, and prostate gland.
The sulfate salt form of metaproterenol, a short-acting and selective sympathomimetic beta-receptor agonist with bronchodilator activity. Metaproterenol sulfate binds beta-2 adrenergic receptors in bronchial smooth muscle and stimulates intracellular adenyl cyclase, thereby increasing the production of cyclic adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, improve mucocliary clearance and reduce inflammatory cell mediator release, especially from mast cells.
A sympathomimetic agent that acts predominantly at alpha-1 adrenergic receptors. It has been used primarily as a vasoconstrictor in the treatment of HYPOTENSION.
Pain in the region of the METATARSUS. It can include pain in the METATARSAL BONES; METATARSOPHALANGEAL JOINT; and/or intermetatarsal joints (TARSAL JOINTS).
The period following ESTRUS during which the phenomena of estrus subside in those animals in which pregnancy or pseudopregnancy does not occur.
A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289)
A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)
A narcotic analgesic with a long onset and duration of action.
A dithiobiurea compound with anti-gonadotropic activity.
A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.
A synthetic steroid with anabolic and androgenic properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1188)
A synthetic steroid with anabolic properties that are more pronounced than its androgenic effects. It has little progestational activity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1188)
A quaternary ammonium compound that acts as an antimuscarinic agent. It has been used in the treatment of PEPTIC ULCER, in gastrointestinal disorders associated with smooth muscle spasm, and in the management of urinary incontinence, and may also be used for the treatment of HYPERHIDROSIS.
Histamine H1 antagonist with sedative action used as a hypnotic and in allergies.
A quinazoline derivative with hypnotic and sedative properties. It has been withdrawn from the market in many countries because of problems with abuse. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)
A carbonic anhydrase inhibitor that is used as a diuretic and in the treatment of glaucoma.
Abnormally increased levels of Methemoglobinemia in the blood. In this form of hemoglobin, there is an oxidized ferric iron (Fe +3) rather than the reduced ferrous form (Fe 2+) that is normally found in hemoglobin. Methemoglobin has a reduced affinity for oxygen, resulting in a reduced ability to release oxygen to tissues.
A heterocyclic organic compound with antibiotic activity. In the body methenamine is converted to formaldehyde, a nonspecific bactericidal agent. Methenamine is typically used long-term to treat chronic urinary tract infections and to prevent the recurrence of infections.
A synthetic steroid that has been used for its anabolic action.
A dopamine agonist and serotonin antagonist. It has been used similarly to BROMOCRIPTINE as a dopamine agonist and also for MIGRAINE DISORDERS therapy.
A thioamide inhibitor of the enzyme thyroid peroxidase (TPO), with antithyroid activity. Upon administration, methimazole inhibits the metabolism of iodide and the iodination of tyrosine residues in the thyroid hormone precursor thyroglobulin by TPO; this prevents the synthesis of the thyroid hormones triiodothyronine (T3) and thyroxine (T4).
A sulfur-containing essential L-amino acid that is important in many body functions.
A serotonin receptor antagonist in the CENTRAL NERVOUS SYSTEM used as an antipsychotic.
A thiosemicarbazone with activity against poxviruses. Methisazone inhibits the synthesis of structural viral proteins and interrupts full assembly of mature virus.
A carbamate with centrally acting muscle relaxant properties. Though the exact mechanism of action of methocarbamol was not established, it's postulated to be via a mechanism similar of carbamate, inhibition of acetylcholinesterase at synapses in the autonomic nervous system, neuromuscular junction, and central nervous system. Methocarbamol has no direct effect on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber.
A rapid, short-acting barbituric acid derivative, with anesthetic activity. Methohexital binds to the chloride ionophore site of the gamma-aminobutyric acid (GABA)-A/chloride ionophore receptor complex, thereby enhancing the inhibitory actions of GABA-A in the brain. This leads to synaptic inhibition, decreased neuronal excitability, and induction of anesthesia. In addition, this agent decreases glutamate (Glu) responses.
Juvenile hormone analog and insect growth regulator used to control insects by disrupting metamorphosis. Has been effective in controlling mosquito larvae.
An antimetabolite and antifolate agent with antineoplastic and immunosuppressant activities. Methotrexate binds to and inhibits the enzyme dihydrofolate reductase, resulting in inhibition of purine nucleotide and thymidylate synthesis and, subsequently, inhibition of DNA and RNA syntheses. Methotrexate also exhibits potent immunosuppressant activity although the mechanism(s) of actions is unclear.
A phenothiazine with pharmacological activity similar to that of both CHLORPROMAZINE and PROMETHAZINE. It has the histamine-antagonist properties of the antihistamines together with CENTRAL NERVOUS SYSTEM effects resembling those of chlorpromazine. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)
An alpha-1 adrenergic agonist that causes prolonged peripheral VASOCONSTRICTION.
A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA ADDUCTS in the presence of ultraviolet A irradiation.
An inhalation anesthetic. Currently, methoxyflurane is rarely used for surgical, obstetric, or dental anesthesia. If so employed, it should be administered with NITROUS OXIDE to achieve a relatively light level of anesthesia, and a neuromuscular blocking agent given concurrently to obtain the desired degree of muscular relaxation. (From AMA Drug Evaluations Annual, 1994, p180)
A benzothiadiazine-sulfonamide derivative belonging to the class of the thiazide diuretics.
A hydrocarbon used as an industrial solvent. It has been used as an aerosal propellent, as a refrigerant and as a local anesthetic. (From Martindale, The Extra Pharmacopoeia, 31st ed, p1403)
A stable, colorless, combustible liquid that emits toxic fumes of sulfoxide when heated to decomposition. Methyl methanesulfonate is used for laboratory purposes as a catalyst in chemical synthesis and has been tested clinically as a cancer chemotherapeutic agent. This substance is an alkylating agent and acts as a mutagen by altering and damaging DNA and is reasonably anticipated to be a human carcinogen. (NCI05)
The covalent chemical or biochemical addition of a methyl group(s) to a compound. (NCI)
Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative.
A phenylalanine derivative and an aromatic amino acid decarboxylase inhibitor with antihypertensive activity. Methyldopa is a prodrug and is metabolized in the central nervous system. The antihypertensive action of methyldopa seems to be attributable to its conversion into alpha-methylnorepinephrine, which is a potent alpha-2 adrenergic agonist that binds to and stimulates potent central inhibitory alpha-2 adrenergic receptors. This results in a decrease in sympathetic outflow and decreased blood pressure.
A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN.
A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology.
A homolog of ERGONOVINE containing one more CH2 group. (Merck Index, 11th ed)
A norepinephrine derivative used as a vasoconstrictor agent.
A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE HYDROCHLORIDE.
A PREDNISOLONE derivative with similar anti-inflammatory action.
A water-soluble ester of METHYLPREDNISOLONE used for cardiac, allergic, and hypoxic emergencies.
A methylated synthetic androgen receptor agonist with anabolic effects. Methyltestosterone, mimicking testosterone, binds to cytosolic androgen receptors, and the subsequent nuclear transfer of the ligand-receptor complex induces transcription initiation of androgen responsive genes. The gene products are responsible for normal growth and development of male sex organs and secondary sex characteristics. The agent also causes retention of nitrogen, sodium, potassium, phosphorus, as well as calcium.
A purine derivative with antineoplastic and anti-angiogenic properties. 6-methylmercaptopurine riboside (6-MMPR) inhibits amidophosphoribosyltransferase, the first committed step in de novo purine synthesis, and inhibits fibroblast growth factor-2 (FGF2)-induced cell proliferation. (NCI04)
A thiourea antithyroid agent that inhibits the synthesis of thyroid hormone. It is used in the treatment of hyperthyroidism.
An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.
A histamine H2 receptor antagonist that is used as an anti-ulcer agent.
A dopamine D2 antagonist that is used as an antiemetic.
A long acting, quinazoline-based sulfonamide thiazide-like, diuretic. Similar to the thiazides, metolazone acts on the distal convoluted tubule (DCT) and inhibits the sodium-chloride symporter, thereby preventing sodium and chloride reabsorption and excretion of water.
A cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties and devoid of intrinsic sympathomimetic activity. Metoprolol antagonizes beta 1-adrenergic receptors in the myocardium, thereby reducing the rate and force of myocardial contraction leading to a reduction in cardiac output. This agent may also reduce the secretion of renin with subsequent reduction in levels of angiotensin II thereby preventing vasoconstriction and aldosterone secretion.
A synthetic non-aromatizable androgen and anabolic steroid. It binds strongly to the androgen receptor and has therefore also been used as an affinity label for this receptor in the prostate and in prostatic tumors.
A solute for density gradient centrifugation offering higher maximum solution density without the problems of increased viscosity. It is also used as a resorbable, non-ionic contrast medium.
A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS.
Abnormal uterine bleeding that is not related to MENSTRUATION, usually in females without regular MENSTRUAL CYCLE. The irregular and unpredictable bleeding usually comes from a dysfunctional ENDOMETRIUM.
A pyridine derivative and a glucocorticoid synthesis inhibitor. Metyrapone inhibits 11-beta-hydroxylase, thereby inhibiting synthesis of cortisol from 11-deoxycortisol and corticosterone from desoxycorticosterone in the adrenal gland. Removal of the negative feedback mechanism exerted by cortisol results in increased adrenocorticotropic hormone (ACTH) secretion by the pituitary gland. In turn, continuing stimulation of adrenal gland by ACTH results in accumulation of corticoid precursors, 11-desoxycortisol and desoxycorticosterone. These metabolites are excreted in urine that maybe used as indicators for pituitary responsiveness.
A local anesthetic and antiarrhythmic (Class IB) agent structurally related to lidocaine. Mexiletine exerts its antiarrhythmic effect by inhibiting the inward sodium current in cardiac cells, thereby reducing the rate of rise of the cardiac action potential (phase 0) and decreases automaticity in the Purkinje fibers. This slows nerve impulses in the heart and stabilizes the heartbeat. Mexiletine's anesthetic activity is due to its ability to block sodium influx in peripheral nerves, thereby reducing the rate and intensity of pain impulses reaching the central nervous system.
A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors.
An antifungal synthetic derivative of imidazole and used in the treatment of candidal skin infections, Miconazole selectively affects the integrity of fungal cell membranes, high in ergosterol content and different in composition from mammalian cells membranes. (NCI04)
A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)
Decreased length and width of the tongue. [pmid:19125428]
A congenital abnormality of the jaws (particularly the mandible) in which they are unusually small. This condition is not always pathological and may correct itself as the patient matures; however, it may also present as a birth defect in multiple syndromes.
The presence of abnormally small extremities.
A toxicology screening result where proliferating cells that are exposed to a genotoxic chemical produce some daughter cells containing cytoplasmic bodies that are comprised of chromosomes or chromosome fragments, which were not sorted properly during mitosis or meiosis, and are bounded by a nuclear membrane.
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.People with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.People with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.Between one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
A congenital defect in which the mouth is unusually small. (Dorland, 27th ed)
A short-acting benzodiazepine derivative with an imidazole structure and with anxiolytic, amnestic, hypnotic, anticonvulsant and sedative properties. Midazolam exerts its effect by binding to the benzodiazepine receptor at the gamma-aminobutyric acid (GABA) receptor-chloride ionophore complex in the central nervous system (CNS). This leads to an increase in the opening of chloride channels, membrane hyperpolarization and increases the inhibitory effect of GABA in the CNS. Midazolam may also interfere with the reuptake of GABA, thereby causing accumulation of GABA in the synaptic cleft.
Atelectasis of the right middle pulmonary lobe, with chronic pneumonitis. (Dorland, 27th ed)
A direct-acting prodrug and sympathomimetic agent with antihypotensive properties. Midodrine is converted to its active metabolite, desglymidodrine by deglycination reaction. Desglymidodrine selectively binds to and activates alpha-1-adrenergic receptors of the arteriolar and venous vasculature. This causes smooth muscle contraction and leads to an elevation of blood pressure. Desglymidodrine diffuses poorly across the blood-brain barrier, and is therefore not associated with effects on the central nervous system (CNS).
A derivative of the synthetic progestin norethindrone with antiprogesterone activity. Mifepristone competitively binds to the progesterone receptor, resulting in inhibition of the effects of endogenous or exogenous progesterone. This agent also exhibits antiglucocorticoid and weak antiandrogenic activities.
A chronic, benign, and usually painless inflammatory swelling of the lacrimal and salivary glands. It is considered by some to include the glandular enlargement associated with other diseases, such as Sjogren's syndrome, sarcoidosis, lupus erythematosus, etc.
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
A small (one mm or less) vesicular, papular or pustular monomorphous rash, which is associated with heat, fever or occlusion of sweat glands.
Densely calcified fluid, most often found radiographically in association with an obstruction.
3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.
A mixture of liquid hydrocarbons obtained from petroleum. It is used as laxative, lubricant, ointment base, and emollient.
Water naturally or artificially infused with mineral salts or gases.
A class of corticosteroid hormones that maintains fluid and electrolyte balance. The main mineralocorticoid is Aldosterone.
A potent direct-acting peripheral vasodilator (VASODILATOR AGENTS) that reduces peripheral resistance and produces a fall in BLOOD PRESSURE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p371)
Abnormal (non-physiological) constriction of the pupil.
Agents causing contraction of the pupil of the eye. Some sources use the term miotics only for the parasympathomimetics but any drug used to induce miosis is included here.
A nitroimidazole that sensitizes normally radio-resistant hypoxic cells to radiation. It may also be directly cytotoxic to hypoxic cells and has been proposed as an antineoplastic.
Infestations with arthropods of the subclass ACARI, superorder Acariformes.
A brominated analog of mannitol with potential antineoplastic activity. Mitobronitol most likely acts through alkylation via derived epoxide groups.
An increase in MITOCHONDRIAL VOLUME due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria.
A soluble substance, usually a protein, that induces mitosis in resting cells, thereby causing cell proliferation.
A guanylhydrazone with potential antineoplastic activity. Mitoguazone competitively inhibits S-adenosyl-L-methionine decarboxylase (SAMD), an enzyme involved in the synthesis of polyamines, resulting in decreased proliferation of tumor cells, antimitochondrial effects, and p53-independent apoptosis. Polyamines, specifically spermine and spermidine, are essential for thymidine kinase production, DNA synthesis, and cell proliferation. (NCI04)
A synthetic derivative of hexitol with antineoplastic and radiosensitizing properties. Mitolactol alkylates DNA via actual or derived epoxide groups, resulting in inhibition of DNA and RNA synthesis. (NCI04)
Any of a class of anti-tumor antibiotics acting as alkylating agents. All mitomycins have the backbone of methyl, aziridine, pyrrolo, indole, and dione moieties. Bioreductively activated mitomycin antibiotics generate oxygen radicals and alkylate DNA, forming inter-strand cross-links and inhibiting DNA synthesis.
A derivative of the insecticide DICHLORODIPHENYLDICHLOROETHANE that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression.
An anthracenedione antibiotic with antineoplastic activity. Mitoxantrone intercalates into and crosslinks DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, resulting in DNA strand breaks and inhibition of DNA repair. Mitoxantrone is less cardiotoxic compared to doxorubicin.
A heart disorder characterized by a defect in mitral valve structure or function.
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
A fairly common and often benign valvular heart disorder characterized by redundancy or hooding of mitral valve leaflets so that they prolapse into the left atrium, often causing mitral regurgitation. It is often a symptomless condition but may be marked by varied symptoms (e.g. chest pain, fatigue, dizziness, dyspnea, or palpitations) leading in some cases to endocarditis or ventricular tachycardia.
Ab abnormal narrowing of the orifice of the mitral valve. [DDD:dbrown]
A syndrome with overlapping clinical features of systemic lupus erythematosus, scleroderma, polymyositis, and Raynaud's phenomenon. The disease is differentially characterized by high serum titers of antibodies to ribonuclease-sensitive extractable (saline soluble) nuclear antigen and a ""speckled"" epidermal nuclear staining pattern on direct immunofluorescence.
A benign or malignant neoplasm that arises from the salivary glands. It is characterized by the presence of epithelial and mesenchymal elements. This category includes pleomorphic adenoma, carcinoma ex pleomorphic adenoma, and carcinosarcoma.
The hydrochloride salt form of sotalol, an ethanolamine derivative with Class III antiarrhythmic and antihypertensive properties. Sotalol hydrochloride is a nonselective beta-adrenergic receptor and potassium channel antagonist. In the heart, this agent inhibits chronotropic and inotropic effects thereby slowing the heart rate and decreasing myocardial contractility. This agent also reduces sinus rate, slows conduction in the atria and in the atrioventricular (AV) node and increases the functional refractory period of the AV node. In the lungs, sotalol inhibits vasodilation and bronchodilation. In addition, this agent inhibits renin release.
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes).Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder.The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability.Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums.Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism).Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome.Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects.
An indole derivative effective in schizophrenia and other psychoses and possibly useful in the treatment of the aggressive type of undersocialized conduct disorder. Molindone has much lower affinity for D2 receptors than most antipsychotic agents and has a relatively low affinity for D1 receptors. It has only low to moderate affinity for cholinergic and alpha-adrenergic receptors. Some electrophysiologic data from animals indicate that molindone has certain characteristics that resemble those of CLOZAPINE. (From AMA Drug Evaluations Annual, 1994, p283)
A common, benign, usually self-limited viral infection of the skin and occasionally the conjunctivae by a poxvirus (MOLLUSCUM CONTAGIOSUM VIRUS). (Dorland, 27th ed)
A morpholinyl sydnone imine ethyl ester, having a nitrogen in place of the keto oxygen. It acts as NITRIC OXIDE DONORS and is a vasodilator that has been used in ANGINA PECTORIS.
Infection of ruminants with tapeworms of the genus Moniezia.
Diseases of Old World and New World monkeys. This term includes diseases of baboons but not of chimpanzees or gorillas (= APE DISEASES).
A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414)
A condition in which an abnormal amount of a single immunoglobulin is present in the serum. Up to 25% of cases of monoclonal gammopathy of undetermined significance (MGUS) progress to a B-cell malignancy or myeloma. MGUS may occur in conjunction with various carcinomas, chronic inflammatory and infectious conditions, and other diseases.
GLYCEROL esterified with a single acyl (FATTY ACIDS) chain.
A chromosomal abnormality consisting of the absence of one chromosome from the normal diploid number.
A derivative of dipyridamole that is a phosphodiesterase inhibitor, with potential antiplatelet activity. Mopidamol inhibits the hydrolysis of cyclic nucleotides, such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), by cyclic nucleotide phosphodiesterases; thus, cAMP- and cGMP-dependent processes are potentiated. This leads to the induction of prostacyclin synthesis, the inhibition of thromboxane B2 synthesis and prevention of platelet activation and aggregation.
Antinematodal agent used mainly for livestock.
An opiate alkaloid isolated from the plant Papaver somniferum and produced synthetically. Morphine binds to and activates specific opiate receptors (delta, mu and kappa), each of which are involved in controlling different brain functions. In the central nervous and gastrointestinal systems, this agent exhibits widespread effects including analgesia, anxiolysis, euphoria, sedation, respiratory depression, and gastrointestinal system smooth muscle contraction. (NCI04)
Strong dependence, both physiological and emotional, upon morphine.
A peptide of about 22-amino acids isolated from the DUODENUM. At low pH it inhibits gastric motor activity, whereas at high pH it has a stimulating effect.
Motion sickness is a common condition characterized by a feeling of unwellness brought on by certain kinds of movement. The usual symptoms include dizziness, pale skin (pallor), and sweating, followed by nausea and vomiting. Affected individuals may also experience rapid breathing (hyperventilation), headache, restlessness, and drowsiness. These symptoms can be triggered by many kinds of motion, particularly traveling in a car, bus, train, airplane, or boat. Amusement park rides, skiing, and virtual reality environments can also induce motion sickness.
Marked impairments in the development of motor coordination such that the impairment interferes with activities of daily living. (From DSM-V)
A chronic endemic form of hypoplasia of the dental enamel caused by drinking water with a high fluorine content during the time of tooth formation, and characterized by defective calcification that gives a white chalky appearance to the enamel, which gradually undergoes brown discoloration. (Jablonski's Dictionary of Dentistry, 1992, p286)
Habitual breathing through the mouth, usually associated with obstruction of nasal passages
A non-neoplastic or neoplastic disorder affecting the oral cavity.
A benign or malignant neoplasm involving the oral cavity and/or the lips.
Having teeth in neither the mandible nor the maxilla.
An abnormality of movement with a neurological basis characterized by changes in coordination and speed of voluntary movements.
Moyamoya is the name given to a cerebral angiographic picture of bilateral intracranial carotid artery occlusion associated with telangiectatic vessels in the region of the basal ganglia. The Japanese word moyamoya means 'something hazy like a puff of cigarette smoke, drifting in the air.' Hemiplegia of sudden onset and epileptic seizures constitute the prevailing presentation in childhood, while subarachnoid bleeding occurs more frequently in adults (summary by Suzuki, 1986). Genetic Heterogeneity of Moyamoya Disease The MYMY1 locus maps to chromosome 3p. See also susceptibility to moyamoya disease-2 (MYMY2; 607151), caused by variation in the RNF213 gene (613768) on chromosome 17q25; MYMY3 (608796), which maps to chromosome 8q23; MYMY5 (614042), caused by mutation in the ACTA2 gene (102620) on chromosome 10q23; and MYMY6 with achalasia (615750), caused by mutation in the GUCY1A3 gene (139396) on chromosome 4q32. See also MYMY4 (300845), an X-linked recessive syndromic disorder characterized by moyamoya disease, short stature, hypergonadotropic hypogonadism, and facial dysmorphism.
Peptides with the ability to stimulate pigmented cells MELANOCYTES in mammals and MELANOPHORES in lower vertebrates. By stimulating the synthesis and distribution of MELANIN in these pigmented cells, they increase coloration of skin and other tissue. MSHs, derived from pro-opiomelanocortin (POMC), are produced by MELANOTROPHS in the INTERMEDIATE LOBE OF PITUITARY; CORTICOTROPHS in the ANTERIOR LOBE OF PITUITARY, and the hypothalamic neurons in the ARCUATE NUCLEUS OF HYPOTHALAMUS.
A hypothalamic tripeptide, enzymatic degradation product of OXYTOCIN, that inhibits the release of MELANOCYTE-STIMULATING HORMONES.
A mucous containing cyst arising from the minor salivary glands in the oral cavity.
Accumulation of mucus within the appendix.
A benign cyst located in the salivary gland that is lined by epithelium and filled with mucoid fluid, tissue, or other material; it is usually caused by duct obstruction.
Kawasaki disease is an acute, self-limited vasculitis of infants and children characterized by prolonged fever unresponsive to antibiotics, polymorphous skin rash, erythema of the oral mucosa, lips, and tongue, erythema of the palms and soles, bilateral conjunctival injection, and cervical lymphadenopathy (Kawasaki, 1967). Coronary artery aneurysms develop in 15 to 25% of those left untreated (Kato et al., 1975, 1996), making Kawasaki disease the leading cause of acquired heart disease among children in developed countries. Treatment with intravenous immunoglobulin (IVIG) abrogates the inflammation in approximately 80% of affected individuals and reduces the aneurysm rate to less than 5%. Cardiac sequelae of the aneurysms include ischemic heart disease, myocardial infarction, and sudden death. Epidemiologic features such as seasonality and clustering of cases suggested an infectious trigger, although no pathogen had been isolated. Several lines of evidence suggested the importance of genetic factors in disease susceptibility and outcome. First, the incidence of Kawasaki disease is 10 to 20 times higher in Japan than in Western countries (Cook et al., 1989). Second, the risk of Kawasaki disease in sibs of affected children is 10 times higher than in the general population, and the incidence of Kawasaki disease in children born to parents with a history of Kawasaki disease is twice as high as that in the general population (Fujita et al., 1989; Uehara et al., 2003). Hata and Onouchi (2009) reviewed current knowledge on Kawasaki disease, including epidemiology, genomewide linkage analysis, and molecular genetics.
A group of inherited lysosomal storage diseases characterized by accumulation of lipids and carbohydrates in the tissues, resulting in mental disabilities and skeletal malformations.
Any agent that dissolves mucus, making it less thick and sticky. This makes it easier for the mucus to drain from the upper respiratory system, be removed through coughing, or be transported through the gastrointestinal (GI) tract.
A group of autosomal recessive or X-linked inherited lysosomal storage disorders affecting the metabolism of mucopolysaccharides, resulting in the accumulation of mucopolysaccharides in the body. Signs and symptoms include organomegaly, mental retardation, abnormal skeletal development, heart disorders, hearing loss, and central nervous system deficiencies.
Mucopolysaccharidosis type II (MPS II; also known as Hunter syndrome) is an X-linked multisystem disorder characterized by glycosaminoglycan (GAG) accumulation. The vast majority of affected individuals are male; on rare occasion heterozygous females manifest findings. Age of onset, disease severity, and rate of progression vary significantly among affected males. In those with early progressive disease, CNS involvement (manifest primarily by progressive cognitive deterioration), progressive airway disease, and cardiac disease usually result in death in the first or second decade of life. In those with slowly progressive disease, the CNS is not (or is minimally) affected, although the effect of GAG accumulation on other organ systems may be early progressive to the same degree as in those who have progressive cognitive decline. Survival into the early adult years with normal intelligence is common in the slowly progressing form of the disease. Additional findings in both forms of MPS II include: short stature; macrocephaly with or without communicating hydrocephalus; macroglossia; hoarse voice; conductive and sensorineural hearing loss; hepatosplenomegaly; dysostosis multiplex; spinal stenosis; and carpal tunnel syndrome.
Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a progressive disorder that primarily affects the brain and spinal cord (central nervous system). Other body systems can also be involved.People with MPS III generally do not display any features of the condition at birth, but they begin to show signs and symptoms of the disorder during early childhood. Affected children often initially have delayed speech and behavior problems. They may become restless, destructive, anxious, or aggressive, and some display features of autism spectrum disorder, which is a condition characterized by difficulty with social interactions and communication. Sleep disturbances are also very common in children with MPS III. This condition causes progressive intellectual disability and the loss of previously acquired skills (developmental regression). In later stages of the disorder, people with MPS III may develop seizures and movement disorders.The physical features of MPS III are less pronounced than those of other types of mucopolysaccharidosis. Individuals with MPS III typically have mildly ""coarse"" facial features, a large head (macrocephaly), a slightly enlarged liver (mild hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Some people with MPS III have short stature, joint stiffness, or mild dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Affected individuals often experience chronic diarrhea and recurrent upper respiratory and ear infections. People with MPS III may also have hearing loss and vision problems.MPS III is divided into types IIIA, IIIB, IIIC, and IIID, which are distinguished by their genetic cause. The different types of MPS III have similar signs and symptoms, although the features of MPS IIIA typically appear earlier in life and progress more rapidly. People with MPS III usually live into adolescence or early adulthood.
Mucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a progressive condition that mainly affects the skeleton. The rate at which symptoms worsen varies among affected individuals.The first signs and symptoms of MPS IV usually become apparent during early childhood. Affected individuals develop various skeletal abnormalities, including short stature, knock knees, and abnormalities of the ribs, chest, spine, hips, and wrists. People with MPS IV often have joints that are loose and very flexible (hypermobile), but they may also have restricted movement in certain joints. A characteristic feature of this condition is underdevelopment (hypoplasia) of a peg-like bone in the neck called the odontoid process. The odontoid process helps stabilize the spinal bones in the neck (cervical vertebrae). Odontoid hypoplasia can lead to misalignment of the cervical vertebrae, which may compress and damage the spinal cord, resulting in paralysis or death.In people with MPS IV, the clear covering of the eye (cornea) typically becomes cloudy, which can cause vision loss. Some affected individuals have recurrent ear infections and hearing loss. The airway may become narrow in some people with MPS IV, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). Other common features of this condition include mildly ""coarse"" facial features, thin tooth enamel, multiple cavities, heart valve abnormalities, a mildly enlarged liver (hepatomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Unlike some other types of mucopolysaccharidosis, MPS IV does not affect intelligence.The life expectancy of individuals with MPS IV depends on the severity of symptoms. Severely affected individuals may survive only until late childhood or adolescence. Those with milder forms of the disorder usually live into adulthood, although their life expectancy may be reduced. Spinal cord compression and airway obstruction are major causes of death in people with MPS IV.
Mucopolysaccharidosis type VI is an autosomal recessive lysosomal storage disorder resulting from a deficiency of arylsulfatase B. Clinical features and severity are variable, but usually include short stature, hepatosplenomegaly, dysostosis multiplex, stiff joints, corneal clouding, cardiac abnormalities, and facial dysmorphism. Intelligence is usually normal (Azevedo et al., 2004).
Infection in humans and animals caused by any fungus in the order Mucorales (e.g., Absidia, Mucor, Rhizopus etc.) There are many clinical types associated with infection of the central nervous system, lung, gastrointestinal tract, skin, orbit and paranasal sinuses. In humans, it usually occurs as an opportunistic infection in patients with a chronic debilitating disease, particularly uncontrolled diabetes, or who are receiving immunosuppressive agents. (From Dorland, 28th ed)
A polypoid lesion that arises from the cervix and contains mucus.
A deficiency in the activities of biotin-dependent enzymes (propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and PYRUVATE CARBOXYLASE) due to one of two defects in BIOTIN metabolism. The neonatal form is due to HOLOCARBOXYLASE SYNTHETASE DEFICIENCY. The late-onset form is due to BIOTINIDASE DEFICIENCY.
Multiple myeloma is a neoplastic plasma cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow microenvironment, monoclonal protein in the blood or urine, and associated organ dysfunction (Palumbo and Anderson, 2011).
A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative.
A progressive autoimmune disorder affecting the central nervous system resulting in demyelination. Patients develop physical and cognitive impairments that correspond with the affected nerve fibers.
A disorder characterized by the presence of two or more identities with distinct patterns of perception and personality which recurrently take control of the person's behavior; this is accompanied by a retrospective gap in memory of important personal information that far exceeds ordinary forgetfulness. The changes in identity are not due to substance use or to a general medical condition.
A contagious viral infection caused by the mumps virus. Symptoms include swollen and tender parotid glands, fever, muscle aches and fatigue. Due to vaccination programs, mumps has become a rare disease.
Vaccines used to prevent infection by MUMPS VIRUS. Best known is the live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had mumps or been immunized with live mumps vaccine. Children are usually immunized with measles-mumps-rubella combination vaccine.
A factitious disorder characterized by habitual presentation for hospital treatment of an apparent acute illness, the patient giving a plausible and dramatic history, all of which is false.
A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.
A neurotoxic isoxazole isolated from species of AMANITA. It is obtained by decarboxylation of IBOTENIC ACID. Muscimol is a potent agonist of GABA-A RECEPTORS and is used mainly as an experimental tool in animal and tissue studies.
A sustained and usually painful contraction of muscle fibers. This may occur as an isolated phenomenon or as a manifestation of an underlying disease process (e.g., UREMIA; HYPOTHYROIDISM; MOTOR NEURON DISEASE; etc.). (From Adams et al., Principles of Neurology, 6th ed, p1398)
A type of paralysis in which a muscle becomes soft and yields to passive stretching, which results from loss of all or practically all peripheral motor nerves that innervated the muscle. Muscle tone is reduced and the affected muscles undergo extreme atrophy within months of the loss of innervation.
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358)
An involuntary, persistent state of firm, tense muscles with marked resistance to passive movement.
A form of muscle hypertonia associated with upper MOTOR NEURON DISEASE. Resistance to passive stretch of a spastic muscle results in minimal initial resistance (a ""free interval"") followed by an incremental increase in muscle tone. Tone increases in proportion to the velocity of stretch. Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. (From Adams et al., Principles of Neurology, 6th ed, p54)
Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.
Spinal muscular atrophy (SMA) is characterized by muscle weakness and atrophy resulting from progressive degeneration and loss of the anterior horn cells in the spinal cord (i.e., lower motor neurons) and the brain stem nuclei. The onset of weakness ranges from before birth to adolescence or young adulthood. The weakness is symmetric, proximal > distal, and progressive. Before the genetic basis of SMA was understood, it was classified into clinical subtypes; however, it is now apparent that the phenotype of SMN1-associated SMA spans a continuum without clear delineation of subtypes. Poor weight gain with growth failure, restrictive lung disease, scoliosis, joint contractures, and sleep difficulties are common complications.
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
A group of inherited progressive muscle disorders characterized by muscle weakness and eventual death of the muscle tissues. Examples include Duchenne muscular dystrophy, Becker's muscular dystrophy, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, and limb-girdle muscular dystrophy.
MUSCULAR DYSTROPHY that occurs in VERTEBRATE animals.
A category of diseases that involve muscles and bones.
Discomfort stemming from muscles, LIGAMENTS, tendons, and bones.
Strong alkylating and immunosuppressive agents whose biological activity is based on the presence of bis(2-chloroethyl)- groups. Although otherwise structurally diverse, the compounds have in common the capacity to contribute alkyl groups to DNA. They are generally highly toxic but include among their number many widely used and effective antineoplastic agents.
The inability to generate oral-verbal expression, despite normal comprehension of speech. This may be associated with BRAIN DISEASES or MENTAL DISORDERS. Organic mutism may be associated with damage to the FRONTAL LOBE; BRAIN STEM; THALAMUS; and CEREBELLUM. Selective mutism is a psychological condition that usually affects children characterized by continuous refusal to speak in social situations by a child who is able and willing to speak to selected persons. Kussmal aphasia refers to mutism in psychosis. (From Fortschr Neurol Psychiatr 1994; 62(9):337-44)
A pyrazole diuretic with long duration and high capacity of action. It was proposed for kidney failure and hypertension but was withdrawn worldwide because of severe neurological effects.
Myasthenia gravis is a disorder that causes weakness of the skeletal muscles, which are muscles that the body uses for movement. The weakness most often starts in the muscles around the eyes, causing drooping of the eyelids (ptosis) and difficulty coordinating eye movements, which results in blurred or double vision. In a form of the disorder called ocular myasthenia, the weakness remains confined to the eye muscles. In most people with myasthenia gravis, however, additional muscles in the face and neck are affected. Affected individuals may have unusual facial expressions, difficulty holding up the head, speech impairment (dysarthria), and chewing and swallowing problems (dysphagia) that may lead to choking, gagging, or drooling.Other muscles in the body are also affected in some people with myasthenia gravis. The muscles of the arms and legs may be involved, causing affected individuals to have changes in their gait or trouble with lifting objects, rising from a seated position, or climbing stairs. The muscle weakness tends to fluctuate over time; it typically worsens with activity and improves with rest.Weakness of the muscles in the chest wall and the muscle that separates the abdomen from the chest cavity (the diaphragm) can cause breathing problems in some people with myasthenia gravis. About 10 percent of people with this disorder experience a potentially life-threatening complication in which these respiratory muscles weaken to the point that breathing is dangerously impaired, and the affected individual requires ventilation assistance. This respiratory failure, called a myasthenic crisis, may be triggered by stresses such as infections or reactions to medications.People can develop myasthenia gravis at any age. For reasons that are unknown, it is most commonly diagnosed in women younger than age 40 and men older than age 60. It is uncommon in children, but some infants born to women with myasthenia gravis show signs and symptoms of the disorder for the first few days or weeks of life. This temporary occurrence of symptoms is called transient neonatal myasthenia gravis.
A cyclic polypeptide antibiotic isolated from culture filtrates of Bacillus subtilis that acts as an antifungal agent.
A nontuberculous infection when occurring in humans. It is characterized by pulmonary disease, lymphadenitis in children, and systemic disease in AIDS patients. Mycobacterium avium-intracellulare infection of birds and swine results in tuberculosis.
Infection due to organisms from the genus Mycobacteria.
Infections with nontuberculous mycobacteria (atypical mycobacteria): M. kansasii, M. marinum, M. scrofulaceum, M. flavescens, M. gordonae, M. obuense, M. gilvum, M. duvali, M. szulgai, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. xenopi (littorale), M. ulcerans, M. buruli, M. terrae, M. fortuitum (minetti, giae), M. chelonae.
Infections with species of the genus MYCOPLASMA.
Infections with bacteria of the order MYCOPLASMATALES.
Mycosis fungoides is a malignant T-cell lymphoma of the skin, first reported (and named) by Alibert (1835). Sezary syndrome is a leukemic variant of mycosis fungoides defined by erythroderma with greater than 80% of the skin showing redness, adenopathy and greater than 1,000 circulating Sezary cells/microliter with a CD4+CD26- or CD4+CD7- phenotype. Sezary cells have a type 2 helper T cell cytokine profile. Sezary syndrome has a median overall survival time of only 2.4 years in patients with Sezary cells at a density of greater than 10,000 cells/microliter or 5.4 years in patients with 1,000-10,000 Sezary cells/microliter. Mycosis fungoides and Sezary syndrome are the most common cutaneous T-cell lymphomas. Sezary syndrome can arise de novo or can appear following years of chronic mycosis fungoides. Both are thought to arise from clonal expansion of CD4+ helper T cells responding to chronic antigen stimulation (summary by Wang et al., 2015).
Agents that dilate the pupil. They may be either sympathomimetics or parasympatholytics.
An inflammatory process affecting the spinal cord. Causes include viral infections, autoimmune disorders, vascular disorders, and toxic agents. Symptoms include weakness, paresthesia, sensory loss, pain, and incontinence.
Inflammation of a transverse portion of the spinal cord characterized by acute or subacute segmental demyelination or necrosis. The condition may occur sporadically, follow an infection or vaccination, or present as a paraneoplastic syndrome (see also ENCEPHALOMYELITIS, ACUTE DISSEMINATED). Clinical manifestations include motor weakness, sensory loss, and incontinence. (Adams et al., Principles of Neurology, 6th ed, pp1242-6)
A partial or complete replacement of the bone marrow stroma by fibrous tissue. It can be a primary bone marrow lesion as part of the chronic myeloproliferative disorders (chronic idiopathic myelofibrosis), a manifestation of acute myeloid leukemia (acute panmyelosis with myelofibrosis), or a secondary phenomenon due to bone marrow involvement by a metastatic tumor (e.g., metastatic breast carcinoma). --2003
An acute myeloid leukemia (AML) characterized by blasts without evidence of maturation to more mature neutrophils. (WHO, 2001)
Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.
The infection of a fly larva (maggot) in human tissue, which most commonly occurs in tropical climates. Affected tissues most commonly include skin, especially if open wounds are present, nasal passages, ears, and eyes.
A granular cell tumor that is confined to the site of origin, without metastatic potential.
Gross necrosis of the myocardium, as a result of interruption of the blood supply to the area, as in coronary thrombosis.
Damage to the MYOCARDIUM resulting from MYOCARDIAL REPERFUSION (restoration of blood flow to ischemic areas of the HEART.) Reperfusion takes place when there is spontaneous thrombolysis, THROMBOLYTIC THERAPY, collateral flow from other coronary vascular beds, or reversal of vasospasm.
Inflammation of the myocardium. [HPO:probinson, pmid:21304213, pmid:22185868, pmid:22361396]
Inflammation of the heart characterized by infiltration of the interstitial tissues by inflammatory cells, histiocytes, and the formation of granulomas. Giant cells are often present.
A rapid, involuntary jerk of a muscle or group of muscles.
A benign or malignant tumor characterized by the presence of cells that show myoepithelial differentiation. Based on its morphologic features, it is classified as benign or malignant. A representative example of benign myoepithelioma is benign salivary gland myoepithelioma. Representative examples of malignant myoepithelioma or myoepithelial carcinoma are malignant breast myoepithelioma and salivary gland myoepithelial carcinoma.
Muscular pain in numerous body regions that can be reproduced by pressure on TRIGGER POINTS, localized hardenings in skeletal muscle tissue. Pain is referred to a location distant from the trigger points. A prime example is the TEMPOROMANDIBULAR JOINT DYSFUNCTION SYNDROME.
A benign mesenchymal neoplasm arising from smooth, skeletal, or cardiac muscle tissue [NCIT:C4882].
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.Nearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.For normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.Nearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.Eye doctors often refer to nearsightedness less than -5 or -6 diopters as ""common myopia."" Nearsightedness of -6 diopters or more is commonly called ""high myopia."" This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term ""pathological myopia"" is used to describe cases in which high myopia leads to tissue damage within the eye.
A general term for a malignant neoplasm derived from muscular tissue. (Stedman, 25th ed)
Idiopathic inflammatory myopathy is a group of disorders characterized by inflammation of the muscles used for movement (skeletal muscles). Idiopathic inflammatory myopathy usually appears in adults between ages 40 and 60 or in children between ages 5 and 15, though it can occur at any age.The primary symptom of idiopathic inflammatory myopathy is muscle weakness, which develops gradually over a period of weeks to months or even years. Other symptoms include joint pain and general tiredness (fatigue).There are several forms of idiopathic inflammatory myopathy, including polymyositis, dermatomyositis, and sporadic inclusion body myositis.Polymyositis and dermatomyositis involve weakness of the muscles closest to the center of the body (proximal muscles), such as the muscles of the hips and thighs, upper arms, and neck. People with these forms of idiopathic inflammatory myopathy may find it difficult to climb stairs, get up from a seated position, or lift items above their head. In some cases, muscle weakness may make swallowing or breathing difficult.Polymyositis and dermatomyositis have similar symptoms, but dermatomyositis is distinguished by a reddish or purplish rash on the eyelids, elbows, knees, or knuckles. Sometimes, abnormal calcium deposits form hard, painful bumps under the skin (calcinosis).In sporadic inclusion body myositis, the muscles most affected are those of the wrists and fingers and the front of the thigh. Affected individuals may frequently stumble while walking and find it difficult to grasp items. As in dermatomyositis and polymyositis, swallowing can be difficult.
A disease characterized by bony deposits or the ossification of muscle tissue.
An involuntary and painless delay in the relaxation of skeletal muscle following contraction or electrical stimulation.
Myotonic dystrophy is an autosomal dominant disorder characterized mainly by myotonia, muscular dystrophy, cataracts, hypogonadism, frontal balding, and ECG changes. The genetic defect in DM1 results from an amplified trinucleotide repeat in the 3-prime untranslated region of a protein kinase gene. Disease severity varies with the number of repeats: normal individuals have 5 to 37 repeats, mildly affected persons have 50 to 150 repeats, patients with classic DM have 100 to 1,000 repeats, and those with congenital onset can have more than 2,000 repeats. The disorder shows genetic anticipation, with expansion of the repeat number dependent on the sex of the transmitting parent. Alleles of 40 to 80 repeats are usually expanded when transmitted by males, whereas only alleles longer than 80 repeats tend to expand in maternal transmissions. Repeat contraction events occur 4.2 to 6.4% of the time (Musova et al., 2009). Genetic Heterogeneity of Myotonic Dystrophy See also myotonic dystrophy-2 (DM2; 602668), which is caused by mutation in the ZNF9 gene (116955) on chromosome 3q21.
Myotonia congenita is characterized by muscle stiffness present from childhood; all striated muscle groups including the extrinsic eye muscles, facial muscles, and tongue may be involved. Stiffness is relieved by repeated contractions of the muscle (the ""warm-up"" phenomenon). Muscles are usually hypertrophic. The autosomal recessive form of myotonia congenita is often associated with more severe symptoms than the autosomal dominant form. Individuals with the autosomal recessive form may have progressive, minor distal weakness and attacks of transient weakness brought on by movement after rest. The age of onset is variable: in autosomal dominant myotonia congenita, onset of symptoms is usually in infancy or early childhood; in the autosomal recessive form, the average age of onset is slightly older. In both, onset may be as late as the third or fourth decade of life.
A cataract occurring as a sequela of myotonic dystrophy.
A condition characterized by a dry, waxy type of swelling (EDEMA) with abnormal deposits of MUCOPOLYSACCHARIDES in the SKIN and other tissues. It is caused by a deficiency of THYROID HORMONES. The skin becomes puffy around the eyes and on the cheeks. The face is dull and expressionless with thickened nose and lips.
A benign neoplasm derived from connective tissue, consisting chiefly of polyhedral and stellate cells that are loosely embedded in a soft mucoid matrix, thereby resembling primitive mesenchymal tissue. It occurs frequently intramuscularly where it may be mistaken for a sarcoma. It appears also in the jaws and the skin. (From Stedman, 25th ed)
An infiltrating malignant soft tissue neoplasm characterized by the presence of immature undifferentiated cells and abundant myxoid stroma formation.
A muscarinic antagonist structurally related to ATROPINE but often considered safer and more effective for inhalation use. It is used for various bronchial disorders, in rhinitis, and as an antiarrhythmic.
A benign, mucus-filled cervical cyst that occurs when mucus-secreting columnar epithelial cells are covered with squamous epithelium.
A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed)
A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for MIGRAINE DISORDERS and for tremor.
A peroxisome proliferator that is used experimentally to promote liver tumors. It has been used as an antihyperlipoproteinemic agent.
A triphenylethylene nonsteroidal agent that acts as a partial estrogen antagonist. Nafoxidine competes with endogenous estrogen for binding to specific estrogen receptors. This agent also inhibits angiogenesis in some tissues by blocking the effects of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF); paradoxically, it may enhance angiogenesis in uterine tissue. Nafoxidine also induces oxidative stress, protein kinase C and calcium signaling. (NCI04)
A drug used in the management of peripheral and cerebral vascular disorders. It is claimed to enhance cellular oxidative capacity and to be a spasmolytic. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1310) It may also be an antagonist at 5HT-2 serotonin receptors.
Diseases of the nail plate and tissues surrounding it. The concept is limited to primates.
Nail-patella syndrome (NPS) involves a classic clinical tetrad of changes in the nails, knees, and elbows, and the presence of iliac horns. Nail changes are the most constant feature of NPS. Nails may be absent, hypoplastic, or dystrophic; ridged longitudinally or horizontally; pitted; discolored; separated into two halves by a longitudinal cleft or ridge of skin; and thin or (less often) thickened. The patellae may be small, irregularly shaped, or absent. Elbow abnormalities may include limitation of extension, pronation, and supination; cubitus valgus; and antecubital pterygia. Iliac horns are bilateral, conical, bony processes that project posteriorly and laterally from the central part of the iliac bones of the pelvis. Renal involvement, first manifest as proteinuria with or without hematuria, occurs in 30%-50% of affected individuals; end-stage renal disease (ESRD) occurs in about 5% of affected individuals. Primary open-angle glaucoma and ocular hypertension occur at increased frequency and at a younger age than in the general population.
A condition in which the nail grows into the nailbed secondary to downward pressure, generally caused by ill-fitting shoes. Symptoms include pain, erythema, and edema, and may result in infection if it remains untreated.
Deformities in nail structure or appearance, including hypertrophy, splitting, clubbing, furrowing, etc. Genetic diseases such as PACHYONYCHIA CONGENITA can result in malformed nails.
An arbovirus infection of sheep and goats transmitted by ticks. It is characterized by high fever and hemorrhagic gastroenteritis.
A narcotic used as a pain medication. It appears to be an agonist at KAPPA RECEPTORS and an antagonist or partial agonist at MU RECEPTORS.
A narcotic antagonist with some agonist properties. It is an antagonist at mu opioid receptors and an agonist at kappa opioid receptors. Given alone it produces a broad spectrum of unpleasant effects and it is considered to be clinically obsolete.
A noroxymorphone derivative with competitive opioid antagonistic property. Naltrexone reverses the effects of opioid analgesics by binding to the various opioid receptors in the central nervous system, including the mu-, kappa- and gamma-opioid receptors. This leads to an inhibition of the typical actions of opioid analgesics, including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependence. Naltrexone is longer-acting and more potent compared to naloxone.
A synthetic, anabolic steroid analog of testosterone. Similar to testosterone, nortestosterone (19-Nortestosterone) binds to and activates specific nuclear receptors. This agent may be used for testosterone replacement therapy in hypogonadal men, in HIV-wasting syndrome, and in other conditions in order to increase nitrogen retention and fat-free muscle mass.
An adrenergic vasoconstrictor agent used as a decongestant.
A white, volatile, solid polycyclic hydrocarbon with a strong mothball odor. Naphthalene is obtained from either coal tar or petroleum distillation and is primarily used to manufacture phthalic anhydride, but is also used in moth repellents. Exposure to naphthalene is associated with hemolytic anemia, damage to the liver and neurological system, cataracts and retinal hemorrhage. Naphthalene is reasonably anticipated to be a human carcinogen and may be associated with an increased risk of developing laryngeal and colorectal cancer. (NCI05)
4(1-Naphthylvinyl)pyridine hydrochloride. Cholinesterase inhibitor. Synonym: YuB 25.
A propionic acid derivative and a non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic and analgesic activities. Naproxen inhibits the activity of the enzymes cyclo-oxygenase I and II, resulting in a decreased formation of precursors of prostaglandins and thromboxanes. The resulting decrease in prostaglandin synthesis is responsible for the therapeutic effects of naproxen. Naproxen also causes a decrease in the formation of thromboxane A2 synthesis, by thromboxane synthase, thereby inhibiting platelet aggregation.
A psychoanalytic term meaning self-love.
A disorder characterized by an enduring pattern of grandiose beliefs and arrogant behavior together with an overwhelming need for admiration and a lack of empathy for (and even exploitation of) others.
A condition characterized by recurrent episodes of daytime somnolence and lapses in consciousness (microsomnias) that may be associated with automatic behaviors and AMNESIA. CATAPLEXY; SLEEP PARALYSIS, and hypnagogic HALLUCINATIONS frequently accompany narcolepsy. The pathophysiology of this disorder includes sleep-onset rapid eye movement (REM) sleep, which normally follows stage III or IV sleep. (From Neurology 1998 Feb;50(2 Suppl 1):S2-S7)
Agents inhibiting the effect of narcotics on the central nervous system.
Disorders related to or resulting from abuse or misuse of OPIOIDS.
Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.
Reduced ability to pass air through the nasal cavity often leading to mouth breathing.
Any hindrance to the passage of air into and out of the nose. The obstruction may be unilateral or bilateral, and may involve any part of the NASAL CAVITY.
A soft and painless polypoid mass that arises from the mucosa in the nasal cavity. It is usually the result of an inflammatory process. It may recur following surgical resection.
A non-neoplastic or neoplastic disorder that affects the nasopharynx. Representative examples include nasopharyngitis, angiofibroma, and carcinoma.
A benign or malignant neoplasm affecting the nasopharynx. Representative examples of benign neoplasms include angiofibroma and squamous papilloma. Representative examples of malignant neoplasms include keratinizing squamous cell carcinoma and nonkeratinizing carcinoma.
An inflammatory process that affects the nasopharynx.
A sensation of unease in the stomach together with an urge to vomit.
Expelling the contents of the stomach and the sensations associated with it. They are symptoms of an underlying disease or condition and not a specific illness.
A disorder caused by an infection with hookworms of the genus Necator, which settle in the host's small intestine, and cause abdominal pain, diarrhea, weight loss, and anemia.
A benign or malignant neoplasm that affects the neck region.
A degenerative disease of the dermal connective tissue characterized by the development of erythematous papules or nodules in the pretibial area. The papules form plaques covered with telangiectatic vessels. More than half of the affected patients have diabetes.
Necrotic changes in the bone tissue due to interruption of blood supply. Most often affecting the epiphysis of the long bones, the necrotic changes result in the collapse and the destruction of the bone structure.
Non-narcotic analgesic chemically similar to ORPHENADRINE. Its mechanism of action is unclear. It is used for the relief of acute and chronic pain. (From Martindale, The Extra Pharmacopoeia, 30th ed, p26)
A syndrome that develops following bilateral adrenalectomy for Cushing syndrome. The signs and symptoms result from the presence of an adenocorticotropin-secreting pituitary gland adenoma, and include enlargement of the sella turcica and pressure on the adjacent structures, and skin hyperpigmentation.
Infections by nematodes, general or unspecified.
An enediyne antineoplastic antibiotic hybrid containing an aminoglycoside chromophore. Zinostatin is isolated from the bacterium Streptomyces carzinostaticus. The aminoglycoside component of zinostatin intercalates into DNA and the benzene diradical intermediate of the enediyne core binds to the minor groove of DNA, resulting in single- and double-strand breaks in DNA and apoptosis. (NCI04)
A constellation of neurobehavioral features observed in a neonate following antenatal exposure to drugs including opioids, benzodiazepines, and selective serotonin reuptake inhibitors.
Diseases existing at birth and often before birth, or that develop during the first month of life (INFANT, NEWBORN, DISEASES), regardless of causation. Of these diseases, those characterized by structural deformities are termed CONGENITAL ABNORMALITIES.
Chronic hepatitis characterized by parenchymal inflammation with formation of large multinucleated hepatocytes in response to a variety of insults to the liver. [PMID:27746622]
Ability of neoplasms to infiltrate and actively destroy surrounding tissue.
The spread or migration of cancer cells from one part of the body (the organ in which it first appeared) to another. The secondary tumor contains cells that are like those in the original (primary) tumor.
The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.
The local implantation of tumor cells by contamination of instruments and surgical equipment during and after surgical resection, resulting in local growth of the cells and tumor formation.
A benign or malignant tissue growth resulting from uncontrolled cell proliferation. Benign neoplastic cells resemble normal cells without exhibiting significant cytologic atypia, while malignant cells exhibit overt signs such as dysplastic features, atypical mitotic figures, necrosis, nuclear pleomorphism, and anaplasia. Representative examples of benign neoplasms include papillomas, cystadenomas, and lipomas; malignant neoplasms include carcinomas, sarcomas, lymphomas, and leukemias.
A collective term for the various histological types of NEOPLASMS. It is more likely to be used by searchers than by indexers and catalogers.
A term that refers to the classification of a neoplastic process according to the anatomic site that is involved.
A usually malignant neoplasm composed of primitive (immature) tissues that resemble fetal tissues. Medulloblastoma, Ependymoblastoma, Pineoblastoma, and Wilms tumor are representative embryonal neoplasms. --2003
Neoplasms composed of connective tissue, including elastic, mucous, reticular, osseous, and cartilaginous tissue. The concept does not refer to neoplasms located in connective tissue.
Neoplasms composed of primordial GERM CELLS of embryonic GONADS or of elements of the germ layers of the EMBRYO, MAMMALIAN. The concept does not refer to neoplasms located in the gonads or present in an embryo or FETUS.
Laboratory tumor models used to study tumor development and treatment.
Neoplasms composed of glandular tissue, an aggregation of epithelial cells that elaborate secretions, and of any type of epithelium itself. The concept does not refer to neoplasms located in the various glands or in epithelial tissue.
Certain tumors that 1, arise in organs that are normally dependent on specific hormones and 2, are stimulated or caused to regress by manipulation of the endocrine environment.
A group of autosomal dominant diseases characterized by the combined occurrence of tumors involving two or more ENDOCRINE GLANDS that secrete PEPTIDE HORMONES or AMINES. These neoplasias are often benign but can be malignant. They are classified by the endocrine glands involved and the degree of aggressiveness. The two major forms are MEN1 and MEN2 with gene mutations on CHROMOSOME 11 and CHROMOSOME 10, respectively.
Two or more abnormal growths of tissue occurring simultaneously and presumed to be of separate origin. The neoplasms may be histologically the same or different, and may be found in the same or different sites.
Neoplasms composed of muscle tissue: skeletal, cardiac, or smooth. The concept does not refer to neoplasms located in muscles.
A neoplasm derived from nervous tissue (not necessarity a neoplasm located in the nervous system).
A neoplasm that develops as a result of exposure to radiation.
Metastases in which the tissue of origin is unknown.
A benign or malignant neoplasm (tumour) originating in the vascular system.
Syndromes resulting from inappropriate production of HORMONES or hormone-like materials by NEOPLASMS in non-endocrine tissues or not by the usual ENDOCRINE GLANDS. Such hormone outputs are called ectopic hormone (HORMONES, ECTOPIC) secretion.
The pathological mechanisms and forms taken by tissue during degeneration into a neoplasm and its subsequent activity.
The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.
A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.
A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.
A group of inherited conditions characterized initially by HEMATURIA and slowly progressing to RENAL INSUFFICIENCY. The most common form is the Alport syndrome (hereditary nephritis with HEARING LOSS) which is caused by mutations in genes for TYPE IV COLLAGEN and defective GLOMERULAR BASEMENT MEMBRANE.
Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.
A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.
A condition characterized by calcification of the renal tissue itself. It is usually seen in distal RENAL TUBULAR ACIDOSIS with calcium deposition in the DISTAL KIDNEY TUBULES and the surrounding interstitium. Nephrocalcinosis causes RENAL INSUFFICIENCY.
Hardening of the KIDNEY due to infiltration by fibrous connective tissue (FIBROSIS), usually caused by renovascular diseases or chronic HYPERTENSION. Nephrosclerosis leads to renal ISCHEMIA.
Pathological processes of the KIDNEY without inflammatory or neoplastic components. Nephrosis may be a primary disorder or secondary complication of other diseases. It is characterized by the NEPHROTIC SYNDROME indicating the presence of PROTEINURIA and HYPOALBUMINEMIA with accompanying EDEMA.
A glomerular disorder characterized by the electron microscopic finding of loss of podocyte foot processes. Light microscopic examination does not show glomerular changes. Patients present with proteinuria and nephrotic syndrome.
A collection of symptoms that include severe edema, proteinuria, and hypoalbuminemia; it is indicative of renal dysfunction.
Mechanical compression of nerves or nerve roots from internal or external causes. These may result in a conduction block to nerve impulses (due to MYELIN SHEATH dysfunction) or axonal loss. The nerve and nerve sheath injuries may be caused by ISCHEMIA; INFLAMMATION; or a direct mechanical effect.
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
A non-neoplastic or neoplastic disorder that affects the brain, spinal cord, or peripheral nerves.
A benign or malignant, primary or metastatic neoplasm involving the central or peripheral nervous system.
An uneasy psychological state; the anxious feeling you have when you have the jitters.
A sporadic or inherited disorder characterized by the focal or diffuse proliferation of the cells of the islets of Langerhans in the pancreas. It results in hyperinsulinemia and hypoglycemia.
A heterogeneous group of congenital spinal anomalies that result from defective closure of the neural tube early in fetal life.
Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.
An episode of acute, severe anxiety or depression associated with an inability to function as normal.
The neurenteric cyst is a rare lesion composed of heterotopic endodermal tissue. During the third week of human embryogenesis, the neurenteric canal unites the yolk sac and the amniotic cavity as it traverses the primitive notochordal plate. Persistence of the normally transient neurenteric canal prevents appropriate separation of endoderm and notochord. This results in a variable degree of communication between neural and enteric epithelium.
A benign nerve sheath tumor composed of Schwann cells.
Neuroblastoma is a solid tumor that originate in neural crest cells of the sympathetic nervous system. Most neuroblastomas originate in the abdomen, and most abdominal neuroblastomas originate in the adrenal gland. Neuroblastomas can also originate in the thorax, usually in the posterior mediastinum.
A clinical syndrome characterized by palpitation, SHORTNESS OF BREATH, labored breathing, subjective complaints of effort and discomfort, all following slight PHYSICAL EXERTION. Other symptoms may be DIZZINESS, tremulousness, SWEATING, and INSOMNIA. Neurocirculatory asthenia is most typically seen as a form of anxiety disorder.
An extremely variable eczematous skin disease that is presumed to be a response to prolonged vigorous scratching, rubbing, or pinching to relieve intense pruritus. It varies in intensity, severity, course, and morphologic expression in different individuals. Neurodermatitis is believed by some to be psychogenic. The circumscribed or localized form is often referred to as lichen simplex chronicus.
An intraneural or extraneural neoplasm arising from nerve tissues and neural sheaths. It is composed of perineurial-like fibroblasts and Schwann cells. It usually presents as a localized cutaneous lesion and less often as a circumscribed peripheral nerve mass. Patients with neurofibromatosis type 1 present with multiple masses. Neurofibromas which arise from major nerves and plexiform neurofibromas are precursor lesions to malignant peripheral nerve sheath tumors.
Neurofibromatosis 1 (NF1) is characterized by multiple café au lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, iris Lisch nodules, and choroidal freckling. About half of people with NF1 have plexiform neurofibromas, but most are internal and not suspected clinically. Learning disabilities are present in at least 50% of individuals with NF1. Less common but potentially more serious manifestations include optic nerve and other central nervous system gliomas, malignant peripheral nerve sheath tumors, scoliosis, tibial dysplasia, and vasculopathy.
Neurofibromatosis 2 (NF2) is characterized by bilateral vestibular schwannomas with associated symptoms of tinnitus, hearing loss, and balance dysfunction. The average age of onset is 18 to 24 years. Almost all affected individuals develop bilateral vestibular schwannomas by age 30 years. Affected individuals may also develop schwannomas of other cranial and peripheral nerves, meningiomas, ependymomas, and, very rarely, astrocytomas. Because NF2 is considered an adult-onset disease, it may be underrecognized in children, in whom skin tumors and ocular findings (retinal hamartoma, thickened optic nerves, cortical wedge cataracts, third cranial nerve palsy) may be the first manifestations. Mononeuropathy that occurs in childhood is an increasingly recognized finding; it frequently presents as a persistent facial palsy or hand/foot drop.
A potentially fatal syndrome associated primarily with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS) which are in turn associated with dopaminergic receptor blockade (see RECEPTORS, DOPAMINE) in the BASAL GANGLIA and HYPOTHALAMUS, and sympathetic dysregulation. Clinical features include diffuse MUSCLE RIGIDITY; TREMOR; high FEVER; diaphoresis; labile blood pressure; cognitive dysfunction; and autonomic disturbances. Serum CPK level elevation and a leukocytosis may also be present. (From Adams et al., Principles of Neurology, 6th ed, p1199; Psychiatr Serv 1998 Sep;49(9):1163-72)
Clinical signs and symptoms caused by nervous system injury or dysfunction.
A tumor made up of nerve cells and nerve fibers. (Dorland, 27th ed)
A benign SCHWANNOMA of the eighth cranial nerve (VESTIBULOCOCHLEAR NERVE), mostly arising from the vestibular branch (VESTIBULAR NERVE) during the fifth or sixth decade of life. Clinical manifestations include HEARING LOSS; HEADACHE; VERTIGO; TINNITUS; and FACIAL PAIN. Bilateral acoustic neuromas are associated with NEUROFIBROMATOSIS 2. (From Adams et al., Principles of Neurology, 6th ed, p673)
Drugs used for their actions on skeletal muscle. Included are agents that act directly on skeletal muscle, those that alter neuromuscular transmission (NEUROMUSCULAR BLOCKING AGENTS), and drugs that act centrally as skeletal muscle relaxants (MUSCLE RELAXANTS, CENTRAL). Drugs used in the treatment of movement disorders are ANTI-DYSKINESIA AGENTS.
Drugs that interrupt transmission of nerve impulses at the skeletal neuromuscular junction. They can be of two types, competitive, stabilizing blockers (NEUROMUSCULAR NONDEPOLARIZING AGENTS) or noncompetitive, depolarizing agents (NEUROMUSCULAR DEPOLARIZING AGENTS). Both prevent acetylcholine from triggering the muscle contraction and they are used as anesthesia adjuvants, as relaxants during electroshock, in convulsive states, etc.
Drugs that interrupt transmission at the skeletal neuromuscular junction by causing sustained depolarization of the motor end plate. These agents are primarily used as adjuvants in surgical anesthesia to cause skeletal muscle relaxation.
A general term encompassing lower MOTOR NEURON DISEASE; PERIPHERAL NERVOUS SYSTEM DISEASES; and certain MUSCULAR DISEASES. Manifestations include MUSCLE WEAKNESS; FASCICULATION; muscle ATROPHY; SPASM; MYOKYMIA; MUSCLE HYPERTONIA, myalgias, and MUSCLE HYPOTONIA.
Neuromyelitis optica is an autoimmune disorder that affects the nerves of the eyes and the central nervous system, which includes the brain and spinal cord. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. In neuromyelitis optica, the autoimmune attack causes inflammation of the nerves, and the resulting damage leads to the signs and symptoms of the condition.Neuromyelitis optica is characterized by optic neuritis, which is inflammation of the nerve that carries information from the eye to the brain (optic nerve). Optic neuritis causes eye pain and vision loss, which can occur in one or both eyes.Neuromyelitis optica is also characterized by transverse myelitis, which is inflammation of the spinal cord. The inflammation associated with transverse myelitis damages the spinal cord, causing a lesion that often extends the length of three or more bones of the spine (vertebrae). In addition, myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses, can be damaged. Transverse myelitis causes weakness, numbness, and paralysis of the arms and legs. Other effects of spinal cord damage can include disturbances in sensations, loss of bladder and bowel control, uncontrollable hiccupping, and nausea. In addition, muscle weakness may make breathing difficult and can cause life-threatening respiratory failure in people with neuromyelitis optica.There are two forms of neuromyelitis optica, the relapsing form and the monophasic form. The relapsing form is most common. This form is characterized by recurrent episodes of optic neuritis and transverse myelitis. These episodes can be months or years apart, and there is usually partial recovery between episodes. However, most affected individuals eventually develop permanent muscle weakness and vision impairment that persist even between episodes. For unknown reasons, approximately nine times more women than men have the relapsing form. The monophasic form, which is less common, causes a single episode of neuromyelitis optica that can last several months. People with this form of the condition can also have lasting muscle weakness or paralysis and vision loss. This form affects men and women equally. The onset of either form of neuromyelitis optica can occur anytime from childhood to adulthood, although the condition most frequently begins in a person's forties.Approximately one-quarter of individuals with neuromyelitis optica have signs or symptoms of another autoimmune disorder such as myasthenia gravis, systemic lupus erythematosus, or Sjögren syndrome. Some scientists believe that a condition described in Japanese patients as optic-spinal multiple sclerosis (or opticospinal multiple sclerosis) that affects the nerves of the eyes and central nervous system is the same as neuromyelitis optica.
A group of slowly progressive inherited disorders affecting motor and sensory peripheral nerves. Subtypes include HMSNs I-VII. HMSN I and II both refer to CHARCOT-MARIE-TOOTH DISEASE. HMSN III refers to hypertrophic neuropathy of infancy. HMSN IV refers to REFSUM DISEASE. HMSN V refers to a condition marked by a hereditary motor and sensory neuropathy associated with spastic paraplegia (see SPASTIC PARAPLEGIA, HEREDITARY). HMSN VI refers to HMSN associated with an inherited optic atrophy (OPTIC ATROPHIES, HEREDITARY), and HMSN VII refers to HMSN associated with retinitis pigmentosa. (From Adams et al., Principles of Neurology, 6th ed, p1343)
A group of inherited disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and clinically by loss of sensation and autonomic dysfunction. There are five subtypes. Type I features autosomal dominant inheritance and distal sensory involvement. Type II is characterized by autosomal inheritance and distal and proximal sensory loss. Type III is DYSAUTONOMIA, FAMILIAL. Type IV features insensitivity to pain, heat intolerance, and mental deficiency. Type V is characterized by a selective loss of pain with intact light touch and vibratory sensation. (From Joynt, Clinical Neurology, 1995, Ch51, pp142-4)
Infection of the brain or spinal cord by Treponema pallidum. It occurs many years following the original infection which remained untreated. Signs and symptoms include abnormal gait, blindness, depression, paralysis, seizures and dementia.
A form of functional mental illness that manifests in distressed emotional reactions such as anxiety, obsessive thoughts, compulsive behaviors, or irrational fears.
A decrease in the number of NEUTROPHILS found in the blood.
Indicates a person who has never been married or whose marriages have been annulled.
A circumscribed stable malformation of the skin and occasionally of the oral mucosa, which is not due to external causes and therefore presumed to be of hereditary origin.
A brown, blue, or gray hamartoma of dermal melanocytes, usually on the skin of the face along the distribution of the ophthalmic and maxillary branches of the trigeminal nerve that is most commonly found in Asian populations and in females and is usually benign. It may also involve the oral or ocular mucosal surfaces, and periosteum.
A neoplasm composed of melanocytes that usually appears as a dark spot on the skin.
A condition caused by infection by the Newcastle disease virus, which may be characterized by conjunctivitis, respiratory illness, and diarrhea.
A water-soluble vitamin belonging to the vitamin B family, which occurs in many animal and plant tissues, with antihyperlipidemic activity. Niacin is converted to its active form niacinamide, which is a component of the coenzymes nicotinamide adenine dinucleotide (NAD) and its phosphate form, NADP. These coenzymes play an important role in tissue respiration and in glycogen, lipid, amino acid, protein, and purine metabolism. Although the exact mechanism of action by which niacin lowers cholesterol is not fully understood, it may act by inhibiting the synthesis of very low density lipoproteins (VLDL), inhibiting the release of free fatty acids from adipose tissue, increasing lipoprotein lipase activity, and reducing the hepatic synthesis of VLDL-C and LDL-C.
An MAO inhibitor that is used as an antidepressive agent.
An equimolar complex of 4,4'-Dinitrocarbanilide and 2-Hydroxy-4,6-dimethylpyrimidine. A coccidiostat for poultry.
A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.
An ergot derivative that has been used as a cerebral vasodilator and in peripheral vascular disease. It may ameliorate cognitive deficits in CEREBROVASCULAR DISORDERS.
A niacin derivative that decreases serum Lp(a) levels.
Proposed fasciolacide. Synonyms: Dertil; Bilevon; Bay 9015.
An antihelmintic that is active against most tapeworms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p48)
An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.
Physical and psychological dependence on nicotine.
A condition which occurs following suspension of nicotine use. Clinical features may include nicotine craving, irritability, anxiety, depression and increased appetite. The onset of symptoms may be rapid with severity proportional to length and amount of nicotine use. Unsuccessful management of symptoms may prompt a return to nicotine use.
2-, 3-, or 4-Pyridinecarboxylic acids. Pyridine derivatives substituted with a carboxy group at the 2-, 3-, or 4-position. The 3-carboxy derivative (NIACIN) is active as a vitamin.
Alcohol analog of NICOTINIC ACID which is a direct-acting peripheral vasodilator that causes flushing and may decrease blood pressure. It is used in vasospasm and threatened GANGRENE.
Acid sphingomyelinase (ASM) deficiency has been categorized in the past as either neuronopathic (Niemann-Pick disease type A [NPD-A]), with death in early childhood, or non-neuronopathic (Niemann-Pick disease type B [NPD-B]). While forms intermediate to these two extremes occur, all ASM deficiency that is not NPD-A is designated in this review as NPD-B, despite its wide range of manifestations and severity. The first symptom in NPD-A is hepatosplenomegaly, usually noted by age three months; over time the liver and spleen become massive. Psychomotor development progresses no further than the 12-month level, after which neurologic deterioration is relentless. A classic cherry-red spot of the macula of the retina, which may not be present in the first few months, is eventually present in all affected children. Interstitial lung disease caused by storage of sphingomyelin in pulmonary macrophages results in frequent respiratory infections and often respiratory failure. Most children succumb before the third year. NPD type B, later in onset and milder in manifestations than NPD type A, is characterized by hepatosplenomegaly with progressive hypersplenism and stable liver dysfunction, gradual deterioration in pulmonary function, osteopenia, and atherogenic lipid profile. Progressive and/or clinically significant neurologic manifestations occur infrequently. Survival to adulthood can occur.
A dihydropyridine calcium channel blocking agent. Nifedipine inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents. (NCI04)
An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.
Local antiprotozoal and antifungal agent that may also be given orally.
A nitrofuran derivative with antiprotozoal and potential antineoplastic activities. Nifurtimox is reduced by cytosol enzymes or flavin-containing microsomal enzymes to a highly reactive nitro anion free radical; autooxidation of the nitro anion free radical generates cytotoxic superoxide anion (02-). In addition, nifurtimox-derived nitro anion free radicals may alkylate macromolecules such as nucleic acids and proteins, resulting in the disruption of their structure and function.
An inability to see clearly in dim light; due to a deficiency of vitamin A or to a retinal disorder.
Occurence of excessive sweating during sleep.
A disturbing dream that occurs during rapid eye movement sleep and results in feelings of strong terror, fear, distress, or anxiety.
A central nervous system stimulant. It was formerly used in the treatment of barbiturate overdose but is now considered to be of no value for such purposes and may be dangerous. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1229)
A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.
A water soluble, 5-nitroimidazole compound with antibacterial and potential radiosensitizing activity. As an oxygen mimetic, nimorazole induces free radical formation and is able to sensitize hypoxic cells to the cytotoxic effects of ionizing radiation. This prevents DNA repair and thus enhances damage to DNA strands; eventually, leading to tumor cell death. Nimorazole is less active but also less toxic than the 2-nitroimidazole compounds, misonidazole and etanidazole.
A nitrosourea with antineoplastic activity. Nimustine alkylates and crosslinks DNA, thereby causing DNA fragmentation, inhibition of protein synthesis, and cell death. (NCI05)
2,2-Dihydroxy-1H-indene-1,3-(2H)-dione. Reagent toxic to skin and mucus membranes. It is used in chemical assay for peptide bonds, i.e., protein determinations and has radiosensitizing properties.
An antischistosomal agent that has become obsolete.
The hydrochloride salt form of alphaprodine, a synthetic piperidine ester, with opioid analgesic activity. Alphaprodine mimics the actions of endogenous neuropeptides by binding to opioid receptors, thereby producing characteristic morphine-like effects via the mu-opioid receptor, including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependence.
A 34-amino acid polypeptide antibiotic produced by Streptococcus lactis. It has been used as a food preservative in canned fruits and vegetables, and cheese.
A dihydropyridine calcium channel antagonist that acts as a potent arterial vasodilator and antihypertensive agent. It is also effective in patients with cardiac failure and angina.
An acridine derivative with potential cytostatic and antitumor activities. Although the exact mechanism of action has not been fully elucidated, nitracrine induces the unwinding of supercoiled DNA and binds to the DNA through intercalation, forming drug-DNA adducts and DNA interstrand crosslinks. This inhibits RNA synthesis, protein production, cell growth, DNA replication and cell proliferation; altogether, this may promote apoptosis. Since cancer cells have increased metabolism and proliferate at an increased rate, nitracrine may induce tumor cell apoptosis.
A benzodiazepine derivative used as an anticonvulsant and hypnotic.
A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.
A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.
An organic compound that contains a cyano moiety (-CN) as a functional group.
Compounds containing FURANS attached to a nitro group.
A synthetic derivative of imidazolidinedione, Nitrofurantoin inhibits bacterial DNA, RNA, and cell wall protein synthesis. Activated by bacterial flavoproteins to intermediates that inactivate bacterial ribosomal proteins, Nitrofurantoin is used prophylactically as a urinary anti-infective agent against most gram-positive and gram-negative organisms and for long-term suppression of infections. (NCI04)
A topical anti-infective agent effective against gram-negative and gram-positive bacteria. It is used for superficial WOUNDS AND INJURIES and skin infections. Nitrofurazone has also been administered orally in the treatment of TRYPANOSOMIASIS.
A group of alkylating agents derived from mustard gas, with the sulfur replaced by nitrogen. They were formerly used as toxicants and vesicants, but now function as antineoplastic agents. These compounds are also powerful mutagens, teratogens, immunosuppressants, and carcinogens.
Also called 4-hydroxy-3-iodo-5-nitrophenylacetate. A haptenic determinant that can be radiolabeled and used as salts and derivatives for investigations of immunogenic specificity studies.
A non-steroidal estrogen antagonist (as the 1:1 citrate) most commonly used as a research tool in animal studies.
A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.
Conversion into nitroso compounds. An example is the reaction of nitrites with amino compounds to form carcinogenic N-nitrosamines.
A class of compounds in which the core molecule is R-NO, where R is UREA.
A naturally occurring gas that is colorless and non flammable. It can be manufactured and used for a variety of things such as a pharmacologic agent to produce anesthesia, a food additive as a propellant, and an additive to fuels to increase available oxygen in combustion.
An antibacterial growth promoter used in animal feeds.
Proposed anthelmintic for fasciola and liver fluke infestations.
Infections with bacteria of the genus NOCARDIA.
A synthetic tubulin-binding agent with antineoplastic activity. Nocodazole binds to beta-tubulin and disrupts microtubule assembly/disassembly dynamics. This prevents mitosis and induces apoptosis in tumor cells. Although nocodazole binding site overlaps with that of colchicine, the two agents are structurally quite different.
A severe gangrenous process occurring predominantly in debilitated and malnourished children, especially in underdeveloped countries. It typically begins as a small vesicle or ulcer on the gingiva that rapidly becomes necrotic and spreads to produce extensive destruction of the buccal and labial mucosa and tissues of the face, which may result in severe disfigurement and even death. Various bacteria have been implicated in the etiology. (Dorland, 27th ed)
An isoquinoline derivative that prevents dopamine reuptake into synaptosomes. The maleate was formerly used in the treatment of depression. It was withdrawn worldwide in 1986 due to the risk of acute hemolytic anemia with intravascular hemolysis resulting from its use. In some cases, renal failure also developed. (From Martindale, The Extra Pharmacopoeia, 30th ed, p266)
Hemolytic anemia that is not mediated by immune mechanisms.
Coronary vasodilator with a novel mechanism of action; proposed as antianginal agent.
Cysts formed from epithelial inclusions in the lines of fusion of the embryonic processes which form the jaws. They include nasopalatine or incisive canal cyst, incisive papilla cyst, globulomaxillary cyst, median palatal cyst, median alveolar cyst, median mandibular cyst, and nasoalveolar cyst.
Noonan syndrome (NS) is characterized by characteristic facies, short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one fourth of affected individuals have mild intellectual disability, and language impairments in general are more common in NS than in the general population.
A bitartrate salt of norepinephrine, a synthetic phenylethylamine that mimics the sympathomimetic actions of the endogenous norepinephrine. Norepinephrine bitartrate acts directly on the alpha- and beta-adrenergic receptors. Clinically, norepinephrine is used as a peripheral vasoconstrictor that causes constriction of arterial and venous beds via its alpha-adrenergic action. It is also used as a potent inotropic and chronotropic stimulator of the heart mediated through its beta-1 adrenergic action.
A naturally occurring catecholamine hormone that functions as a neurotransmitter in the sympathetic nervous system. Norepinephrine directly stimulates adrenergic receptors. Stimulation of alpha-adrenergic receptors causes vasoconstriction of the radial smooth muscle of the iris, arteries, arterioles, veins, urinary bladder, and the sphincter of the gastrointestinal tract. Stimulation of beta-1 adrenergic receptors causes an increase in myocardial contractility, heart rate, automaticity, and atrioventricular (AV) conduction while stimulation of beta-2 adrenergic receptors causes bronchiolar and vascular smooth muscle dilatation.
A synthetic hormone with anabolic and androgenic properties and moderate progestational activity.
A synthetic progestational hormone with actions similar to those of PROGESTERONE but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception.
A synthetic progestational hormone with actions and uses similar to those of PROGESTERONE. It has been used in the treatment of functional uterine bleeding and endometriosis. As a contraceptive, it has usually been administered in combination with MESTRANOL.
A FENFLURAMINE analog that inhibits serotonin uptake and may provoke release of serotonin. It is used as an appetite depressant and an experimental tool in animal studies.
A synthetic progestational agent with actions similar to those of PROGESTERONE. This racemic or (+-)-form has about half the potency of the levo form (LEVONORGESTREL). Norgestrel is used as a contraceptive, ovulation inhibitor, and for the control of menstrual disorders and endometriosis.
A synthetic steroid with progestational and contraceptive activities.
An alpha-adrenergic sympathomimetic amine, biosynthesized from tyramine in the CNS and platelets and also in invertebrate nervous systems. It is used to treat hypotension and as a cardiotonic. The natural D(-) form is more potent than the L(+) form in producing cardiovascular adrenergic responses. It is also a neurotransmitter in some invertebrates.
A metabolite of AMITRIPTYLINE that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions.
A rare, severe form of scabies that is associated with immunosuppression. It is characterized by an immense number of mites and hyperkeratotic crusted lesions, and is usually accompanied by lymphadenopathy and eosinophilia.
A naturally occurring opium alkaloid that is a centrally acting antitussive agent.
Disorders of the nose, general or unspecified.
Tumor (An abnormal mass of tissue resulting from abnormally dividing cells) of the nasal cavity. [HPO:probinson]
Medicines whose effectiveness is unproven and whose ingredients are often secret.
Local antibacterial that probably acts by releasing formaldehyde in aqueous solutions. It is used for THERAPEUTIC IRRIGATION of infected body cavities - bladder, peritoneum, etc. and as a spray for burns.
The reformation of all, or part of, the native conformation of a nucleic acid molecule after the molecule has undergone denaturation.
A loss of the sensation of feeling in an area of the body.
Conclusions derived from the nursing assessment that establish a health status profile for the patient and from which nursing interventions may be ordered.
A collective term for nutritional disorders resulting from poor absorption or nutritional imbalance, and metabolic disorders resulting from defects in biosynthesis (ANABOLISM) or breakdown (CATABOLISM) of endogenous substances.
Abnormally increased production of urine during the night leading to an unusually frequent need to urinate.
A beta-adrenergic agonist. Nylidrin causes peripheral vasodilation, a positive inotropic effect, and increased gastric volume of gastric juice. It is used in the treatment of peripheral vascular disorders and premature labor.
Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. (Adams et al., Principles of Neurology, 6th ed, p272)
A reagent that forms fluorescent conjugation products with primary amines. It is used for the detection of many biogenic amines, peptides, and proteins in nanogram quantities in body fluids.
A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).
An excess of body weight, normally defined as an individual with a body mass index greater than 35 or a body weight greater than one hundred percent of ideal body weight.
Cholinesterase reactivator occurring in two interchangeable isomeric forms, syn and anti.
Obsessive-compulsive disorder (OCD) is characterized by recurring obsessions and/or compulsions and has been estimated to affect nearly 5 million people in the United States (Karno et al., 1988). Evidence for a strong genetic component in OCD comes from twin studies, family genetics studies, and segregation analyses, as reviewed by Alsobrook et al. (2002). Zhang et al. (2002) suggested that hoarding is likely to be an evolutionarily conserved trait that, in times of adversity, was associated with increased survival and reproductive fitness. However, extreme forms of this trait are associated with marked disability and poor response to treatment (Black et al., 1998; Mataix-Cols et al., 1999).
Blockage of the normal flow of the contents of an anatomical passageway.
A recurrent contact dermatitis caused by substances found in the work place.
Diseases caused by factors involved in one's employment.
A disorder characterized by bluish-black discoloration of the cartilaginous tissues due to accumulation of homogentisic acid. It is associated with alkaptonuria. Signs and symptoms include dark urine, skin pigmentation, and arthritis.
A potent, long-acting synthetic SOMATOSTATIN octapeptide analog that inhibits secretion of GROWTH HORMONE and is used to treat hormone-secreting tumors; DIABETES MELLITUS; HYPOTENSION, ORTHOSTATIC; HYPERINSULINISM; hypergastrinemia; and small bowel fistula.
A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma.
Abnormally low intraocular pressure often related to chronic inflammation (uveitis).
Disorders that feature impairment of eye movements as a primary manifestation of disease. These conditions may be divided into infranuclear, nuclear, and supranuclear disorders. Diseases of the eye muscles or oculomotor cranial nerves (III, IV, and VI) are considered infranuclear. Nuclear disorders are caused by disease of the oculomotor, trochlear, or abducens nuclei in the BRAIN STEM. Supranuclear disorders are produced by dysfunction of higher order sensory and motor systems that control eye movements, including neural networks in the CEREBRAL CORTEX; BASAL GANGLIA; CEREBELLUM; and BRAIN STEM. Ocular torticollis refers to a head tilt that is caused by an ocular misalignment. Opsoclonus refers to rapid, conjugate oscillations of the eyes in multiple directions, which may occur as a parainfectious or paraneoplastic condition (e.g., OPSOCLONUS-MYOCLONUS SYNDROME). (Adams et al., Principles of Neurology, 6th ed, p240)
Lowe syndrome (oculocerebrorenal syndrome) is characterized by involvement of the eyes, central nervous system, and kidneys. Dense congenital cataracts are found in all affected boys and infantile glaucoma in approximately 50%. All boys have impaired vision; corrected acuity is rarely better than 20/100. Generalized hypotonia is noted at birth and is of central (brain) origin. Deep tendon reflexes are usually absent. Hypotonia may slowly improve with age, but normal motor tone and strength are never achieved. Motor milestones are delayed. Almost all affected males have some degree of intellectual disability; 10%-25% function in the low-normal or borderline range, approximately 25% in the mild-to-moderate range, and 50%-65% in the severe-to-profound range of intellectual disability. Affected males have varying degrees of proximal renal tubular dysfunction of the Fanconi type, including low molecular-weight (LMW) proteinuria, aminoaciduria, bicarbonate wasting and renal tubular acidosis, phosphaturia with hypophosphatemia and renal rickets, hypercalciuria, sodium and potassium wasting, and polyuria. The features of symptomatic Fanconi syndrome do not usually become manifest until after the first few months of life, except for LMW proteinuria. Glomerulosclerosis associated with chronic tubular injury usually results in slowly progressive chronic renal failure and end-stage renal disease between the second and fourth decades of life.
Diseases of the oculomotor nerve or nucleus that result in weakness or paralysis of the superior rectus, inferior rectus, medial rectus, inferior oblique, or levator palpebrae muscles, or impaired parasympathetic innervation to the pupil. With a complete oculomotor palsy, the eyelid will be paralyzed, the eye will be in an abducted and inferior position, and the pupil will be markedly dilated. Commonly associated conditions include neoplasms, CRANIOCEREBRAL TRAUMA, ischemia (especially in association with DIABETES MELLITUS), and aneurysmal compression. (From Adams et al., Principles of Neurology, 6th ed, p270)
A cyst in the jaw that arises from tissues of tooth development.
A benign or malignant neoplasm arising from tooth-forming tissues. It occurs in the maxillofacial skeleton or the gingiva. Benign tumors are slow growing and are not associated with specific clinical symptoms. Pain is absent or slight. Malignant tumors are usually associated with rapid swelling and pain.
A benign, slow growing, and painless hamartomatous tumor occurring in tooth-bearing areas of the jaws. According to the presence or absence of tooth-like structures, it is classified as complex type or compound type. Odontoma of complex type is characterized by the presence of enamel and dentin and the absence of tooth-like structures. It is treated with local excision. If it is incompletely removed, it may recur. Odontoma of compound type is characterized by the presence of tooth-like structures. It is treated by local excision. Recurrences have not been reported.
Infection of the intestinal tract with worms of the genus OESOPHAGOSTOMUM. This condition occurs mainly in animals other than man.
An oil from flower buds of SYZYGIUM trees which contains large amounts of EUGENOL.
An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)
An oligodendroglioma in which there is insufficient information on the IDH genes and 1p/19q codeletion status.
A condition of suboptimal concentration of SPERMATOZOA in the ejaculated SEMEN to ensure successful FERTILIZATION of an OVUM. In humans, oligospermia is defined as a sperm count below 20 million per milliliter semen.
A group of inherited and sporadic disorders which share progressive ataxia in combination with atrophy of the CEREBELLUM; PONS; and inferior olivary nuclei. Additional clinical features may include MUSCLE RIGIDITY; NYSTAGMUS, PATHOLOGIC; RETINAL DEGENERATION; MUSCLE SPASTICITY; DEMENTIA; URINARY INCONTINENCE; and OPHTHALMOPLEGIA. The familial form has an earlier onset (second decade) and may feature spinal cord atrophy. The sporadic form tends to present in the fifth or sixth decade, and is considered a clinical subtype of MULTIPLE SYSTEM ATROPHY. (From Adams et al., Principles of Neurology, 6th ed, p1085)
A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.
Inflammation of the umbilical cord stump in newborns.
A disease caused by infection with Onchocerca volvulus; symptoms may include pruritis and blindness.
Filarial infection of the eyes transmitted from person to person by bites of Onchocerca volvulus-infected black flies. The microfilariae of Onchocerca are thus deposited beneath the skin. They migrate through various tissues including the eye. Those persons infected have impaired vision and up to 20% are blind. The incidence of eye lesions has been reported to be as high as 30% in Central America and parts of Africa.
An inflammation of the ovary or ovaries.
The quality of being opaque to a degree; the degree to which something reduces the passage of light.
Inflammation of the conjunctiva in a newborn due to chemical or infectious causes. Aseptic conjunctivitis is often related to the use of prophylactic medications for infectious conjunctivitis. Septic conjunctivitis is related to perinatal exposure to microorganisms.
Granulomatous uveitis which follows in one eye after a penetrating injury to the other eye; the secondarily affected eye is called the sympathizing eye, and the injured eye is called the exciting or activating eye.
Paralysis of one or more extraocular muscles that are responsible for eye movements.
A tricyclic antidepressant with actions similar to AMITRIPTYLINE.
Infection with flukes of the genus Opisthorchis.
The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few - MORPHINE; CODEINE; and PAPAVERINE - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic.
An infection that is caused by a pathogen that would generally not be able to cause an infection in a host with a normal immune system. Such pathogens take advantage of the opportunity, so to speak, that is provided by a weakened immune system. [HPO:probinson]
A behavior disorder characterized by a persistent pattern of defiant, disobedient, and hostile behavior towards authority figures, manifested by a frequent loss of temper, arguing, becoming angry or vindictive, or other negativistic behaviors.
A disorder characterized by loss of optic nerve fibers. It may be inherited or acquired. Acquired causes include ischemia, optic nerve neuropathy, glaucoma, trauma, radiation, brain tumors, and multiple sclerosis. It leads to vision disturbances.
A family of inherited disorders characterized by progressive loss of vision secondary to death of the retinal ganglion cell axons that comprise the optic nerve.
Optic disc drusen are acellular, calcified deposits within the optic nerve head. Optic disc drusen are congenital and developmental anomalies of the optic nerve head, representing hyaline-containing bodies that, over time, appear as elevated, lumpy irregularities on the anterior portion of the optic nerve.
A non-neoplastic or neoplastic disorder affecting the optic nerve (second cranial nerve).
A disorder characterized by inflammation of the optic nerve. Causes include autoimmune disorders, infections, toxins, drugs, and multiple sclerosis. It may manifest with acute loss of vision and pain.
The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease.
Bleeding from the blood vessels of the mouth, which may occur as a result of injuries to the mouth, accidents in oral surgery, or diseases of the gums.
Disorders of the mouth attendant upon non-oral disease or injury.
Chronic, progressive, debilitating and non-reversible fibrosis of the submucosal tissues of the mouth. It is associated with chewing betel quid, a habit practiced in Southeast Asia and India. It is a precancerous condition and results in rigidity of the jaws and inability of the affected individual to open the mouth.
Irreversible FIBROSIS of the submucosal tissue of the MOUTH.
Diseases of the bony orbit and contents except the eyeball.
A benign or malignant neoplasm that affects the orbit.
Inflammation of a TESTIS. It has many features of EPIDIDYMITIS, such as swollen SCROTUM; PAIN; PYURIA; and FEVER. It is usually related to infections in the URINARY TRACT, which likely spread to the EPIDIDYMIS and then the TESTIS through either the VAS DEFERENS or the lymphatics of the SPERMATIC CORD.
A beta-2 adrenergic agonist used in the treatment of ASTHMA and BRONCHIAL SPASM.
A mental disorder caused by intrinsic disease which is characterized by acute or chronic impairment of intellectual functioning, behavior, mood or judgment. It is attributable to a medical etiology and excludes a primary psychiatric cause. A chronic course usually correlates to a poorer prognosis.
A mental disorder caused by intrinsic disease which is characterized by persistent or recurrent irrational beliefs. Consciousness and memory are not affected. It may be broadly classified as a psychotic disorder due to a general medical condition.
Any decrease in mental functioning in which the cause is not attributable to psychiatric illness, which includes damage from physical trauma, anoxic injury, damage from chemicals or toxins, infection, cancer, and degenerative diseases, including Alzheimer's disease, Huntington's disease, Parkinson's disease, and Creutzfeldt-Jakob disease.
A mental disorder caused by intrinsic disease which is characterized by persistent alterations in mood that are directly attributable to the disease itself rather than a response to knowledge of the disease or other co-morbidity. It may be broadly classified as a depressive or bipolar disorder due to a general medical condition.
A mental disorder caused by intrinsic disease which is characterized by persistent alteration of a known behavioral pattern. Changes in emotional stability, motivation, judgment or impulse control are usually noted. It is broadly classified as a personality change due to a general medical condition.
A change in the ability to obtain orgasm or in the quality of the orgasmic sensation.
A nitroimidazole antiprotozoal agent used in ameba and trichomonas infections. It is partially plasma-bound and also has radiation-sensitizing action.
A synthetic analog of vasopressin with ORNITHINE substitution at residue 8 of the cyclic nonapeptide. It is used as a local vasoconstrictor and hemostatic.
A naturally occurring amino acid found in meat, fish, dairy and eggs. Ornithine is one of the key reactants in the urea cycle that is responsible for 80% of the nitrogen excretion in the body. Ornithine enhances liver function and helps detoxify harmful substances.
Disease caused by the Chlamydophila psittaci bacteria, usually transmitted from birds to humans.
A fistula between the maxillary sinus and the oral cavity.
A benign or malignant neoplasm that affects the oropharynx.
An intermediate product in PYRIMIDINE synthesis which plays a role in chemical conversions between DIHYDROFOLATE and TETRAHYDROFOLATE.
An infection that is caused by Bartonella bacilliformis, which is transmitted to humans from infected sandflies. The acute phase (Oroya Fever) is characterized by fever, headache, myalgia, enlargement of the lymph nodes, and anemia. The chronic phase (verruga peruana/Peruvian wart) is characterized by benign, eruptive lesions that are bleeding and pruritic, arthralgia, and malaise.
A muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm.
The citrate salt form of orphenadrine with a muscle relaxant property. Although the mechanism of action has not been fully elucidated, orphenadrine citrate appears to block cholinergic receptors, thereby interfering with the transmission of nerve impulses from the spinal cord to the muscles. It does not produce myoneural block, nor does it affect crossed extensor reflexes.
Virus diseases caused by the ORTHOMYXOVIRIDAE.
Morbus Osgood-Schlatter is a Juvenile aseptic necrosis affecting the Tuberositas tibiae.
Formation of abnormal, extraskeletal bony tissue, i.e., the presence of bone in soft tissue where bone normally does not exist.
Paget disease of bone is a disorder that causes bones to grow larger and weaker than normal. Affected bones may be misshapen and easily broken (fractured).The classic form of Paget disease of bone typically appears in middle age or later. It usually occurs in one or a few bones and does not spread from one bone to another. Any bones can be affected, although the disease most commonly affects bones in the spine, pelvis, skull, or legs.Many people with classic Paget disease of bone do not experience any symptoms associated with their bone abnormalities. The disease is often diagnosed unexpectedly by x-rays or laboratory tests done for other reasons. People who develop symptoms are most likely to experience pain. The affected bones may themselves be painful, or pain may be caused by arthritis in nearby joints. Arthritis results when the distortion of bones, particularly weight-bearing bones in the legs, causes extra wear and tear on the joints. Arthritis most frequently affects the knees and hips in people with this disease.Other complications of Paget disease of bone depend on which bones are affected. If the disease occurs in bones of the skull, it can cause an enlarged head, hearing loss, headaches, and dizziness. If the disease affects bones in the spine, it can lead to numbness and tingling (due to pinched nerves) and abnormal spinal curvature. In the leg bones, the disease can cause bowed legs and difficulty walking.A rare type of bone cancer called osteosarcoma has been associated with Paget disease of bone. This type of cancer probably occurs in less than 1 in 1,000 people with this disease.Early-onset Paget disease of bone is a less common form of the disease that appears in a person's teens or twenties. Its features are similar to those of the classic form of the disease, although it is more likely to affect the skull, spine, and ribs (the axial skeleton) and the small bones of the hands. The early-onset form of the disorder is also associated with hearing loss early in life.
A disorder that is characterized by bone cysts and fractures, resulting from hyperparathyroidism.
Degeneration (wear and tear) of articular cartilage, i.e., of the joint surface. Joint degeneration may be accompanied by osteophytes (bone overgrowth), narrowing of the joint space, regions of sclerosis at the joint surface, or joint deformity.
Noninflammatory degenerative disease of the hip joint which usually appears in late middle or old age. It is characterized by growth or maturational disturbances in the femoral neck and head, as well as acetabular dysplasia. A dominant symptom is pain on weight-bearing or motion.
A condition chiefly characterized by thickening of the skin of the head and distal extremities, deep folds and furrows of the skin of the forehead, cheeks, and scalp, SEBORRHEA; HYPERHIDROSIS; periostosis of the long bones, digital clubbing, and spadelike enlargement of the hands and feet. It is more prevalent in the male, and is usually first evident during adolescence. Inheritance is primarily autosomal recessive, but an autosomal dominant form exists.
Symmetrical osteitis of the four limbs, chiefly localized to the phalanges and the terminal epiphyses of the long bones of the forearm and leg, sometimes extending to the proximal ends of the limbs and the flat bones, and accompanied by dorsal kyphosis and joint involvement. It is often secondary to chronic conditions of the lungs and heart. (Dorland, 27th ed)
A benign, painful, tumor of bone characterized by the formation of osteoid tissue, primitive bone and calcified tissue.
Inflammation of a bone and its overlaying CARTILAGE.
A joint disorder caused by blood deprivation in the subchondral bone causing the subchondral bone to die in a process called avascular necrosis. The bone is then reabsorbed by the body, leaving the articular cartilage it supported prone to damage. The result is fragmentation (dissection) of both cartilage and bone, and the free movement of these osteochondral fragments within the joint space, causing pain and further damage.
A general term describing features characterized by abnormal development of bones and connective tissues. [HPO:probinson]
A cartilage capped bony outgrowth of a long bone. Osteochondroma arises on the external surface of bone containing a marrow cavity that is continuous with that of the underlying bone.
A condition that is characterized by defective bone growth that affects the growth centers of bone.
Syndromes of bone destruction where the cause is not obvious such as neoplasia, infection, or trauma. The destruction follows various patterns: massive (Gorham disease), multicentric (HAJDU-CHENEY SYNDROME), or carpal/tarsal.
A benign tumor composed of bone tissue or a hard tumor of bonelike structure developing on a bone (homoplastic osteoma) or on other structures (heteroplastic osteoma). (From Dorland, 27th ed)
A benign osteoblastic tumor with central vascularized nidus surrounded by normal reactive bone. It occurs especially in second decade of life most commonly in the femoral neck but can occur in any bone and any site within a bone.
A metabolic bone disease that results from either a deficiency in vitamin D, or an abnormality in the metabolism of vitamin D, or a deficiency of calcium in the diet. The most common symptoms are bone pain and muscle weakness. When it occurs in children it is commonly referred to as rickets. (Diagnostic Surgical Pathology, 3rd ed.) --2003
An acute or chronic inflammation of the bone and its structures due to infection with pyogenic bacteria.
Death of a bone or part of a bone, either atraumatic or posttraumatic.
Decreased calcification or density of bone tissue.
A rare genetic disorder inherited in an autosomal dominant, autosomal recessive, or X-linked recessive pattern. In the majority of cases it is caused by mutations in the CLCN7, TCIRG1, or IKBKG genes. It is characterized by excessive bone formation due to the failure of osteoclasts to resorb bone. It manifests with deformities, fractures, hepatosplenomegaly, anemia, and extramedullary hematopoiesis.
A rare autosomal dominant inherited disorder characterized by the presence of small areas of increased density throughout the bones.
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO, osteoporosis is characterized by a value of BMD 2.5 standard deviations or more below the young adult mean. [HPO:curators]
Metabolic disorder associated with fractures of the femoral neck, vertebrae, and distal forearm. It occurs commonly in women within 15-20 years after menopause, and is caused by factors associated with menopause including estrogen deficiency.
Necrosis of bone following exposure to a source of radiation.
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
A disease of herbivorous mammals, particularly cattle and sheep, caused by stomach worms of the genus OSTERTAGIA.
Inflammation of the ear, which may be marked by pain (EARACHE), fever, HEARING DISORDERS, and VERTIGO. Inflammation of the external ear is OTITIS EXTERNA; of the middle ear, OTITIS MEDIA; of the inner ear, LABYRINTHITIS.
Inflammation of the OUTER EAR including the external EAR CANAL, cartilages of the auricle (EAR CARTILAGE), and the TYMPANIC MEMBRANE.
Inflammation of the MIDDLE EAR including the AUDITORY OSSICLES and the EUSTACHIAN TUBE.
Inflammation of the middle ear with a clear pale yellow-colored transudate.
Inflammation of the middle ear with purulent discharge.
Fungus infection of the external ear, usually by ASPERGILLUS species
Pathological processes of the ear, the nose, and the throat, also known as the ENT diseases.
A general concept for tumors or cancer of any part of the EAR; the NOSE; the THROAT; and the PHARYNX. It is used when there is no specific heading.
Formation of spongy bone in the labyrinth capsule which can progress toward the STAPES (stapedial fixation) or anteriorly toward the COCHLEA leading to conductive, sensorineural, or mixed HEARING LOSS. Several genes are associated with familial otosclerosis with varied clinical signs.
A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.
A cyst that arises from the ovary. Representative examples include simple, complex, corpus luteum, and endometrioid cysts. Symptoms include pelvic and abdominal pain and irregular periods.
An anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine causes worms to shift from the mesenteric veins to the liver where the male worms are retained; the female worms return to the mesentery, but can no longer release eggs. (From Martindale, The Extra Pharmacopoeia, 31st ed, p121)
A synthetic hormone with anabolic and androgenic properties.
A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia.
Immunologic adjuvant and sensitizing agent.
The process of oxidizing; the addition of oxygen to a compound accompanied by a loss of electrons.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds.
A modulator of 5-fluorouracil (5-FU) activity and inhibitor of the enzyme orotate phosphoribosyl-transferase (OPRT), with chemoprotective activity. Oteracil preferentially localizes in the gastrointestinal (GI) tract where it inhibits OPRT, thereby decreasing metabolism of 5-FU into its active metabolite 5-fluorouridine-5'-monophosphate (FUMP). This decreases activated 5-FU-related gastrointestinal toxicity.
A non-hydrolyzed muscarinic agonist used as a research tool.
A beta-adrenergic antagonist used in the treatment of hypertension, angina pectoris, arrhythmias, and anxiety.
Oxycephaly (from Greek oxus, sharp, and kephalos, head) refers to a conical or pointed shape of the skull.
Anthelmintic used in grazing animals for fasciola and cestode infestations.
A semi-synthetic, morphine-like opioid alkaloid with analgesic activity. Oxycodone exerts its analgesic activity by binding to the mu-receptors in the central nervous system (CNS), thereby mimicking the effects of endogenous opioids. Binding of the opiate receptor stimulates the exchange of GTP for GDP on the G-protein complex and inhibits adenylate cyclase, thereby preventing cAMP production. Subsequently, the release of nociceptive neurotransmitters, such as substance P, gamma-aminobutyric acid (GABA), dopamine, acetylcholine, and noradrenaline, is inhibited. Oxycodone also inhibits the release of vasopressin, somatostatin, insulin, and glucagon. In addition, oxycodone closes N-type voltage-gated calcium channels and opens G-protein-coupled inwardly rectifying potassium channels resulting in hyperpolarization and reduction of neuronal excitability.
A drug used in the treatment of angina pectoris, heart failure, conduction defects, and myocardial infarction. It is a partial agonist at beta adrenergic receptors and acts as a coronary vasodilator and cardiotonic agent.
An element with atomic symbol O, atomic number 8, and atomic weight 16.
Stable oxygen atoms that have the same atomic number as the element oxygen, but differ in atomic weight. O-17 and 18 are stable oxygen isotopes.
A direct acting sympathomimetic used as a vasoconstrictor to relieve nasal congestion. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1251)
A synthetic hormone with anabolic and androgenic properties. It is used mainly in the treatment of anemias. According to the Fourth Annual Report on Carcinogens (NTP 85-002), this compound may reasonably be anticipated to be a carcinogen. (From Merck Index, 11th ed)
A semisynthetic narcotic analgesic related to hydromorphone and other opiates, Oxymorphone, hydroxy-dihydromorphinone, affects the central nervous system and smooth muscles by activation of specific opiate receptors. Similar to morphine, but more potent and without cough suppressant activity, it is used in treatment of moderate to severe pain, including obstetrical pain, or as an adjunct to anaesthesia. (NCI04)
A non-steroidal anti-inflammatory drug. Oxyphenbutazone eyedrops have been used abroad in the management of postoperative ocular inflammation, superficial eye injuries, and episcleritis. (From AMA, Drug Evaluations Annual, 1994, p2000) It had been used by mouth in rheumatic disorders such as ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis but such use is no longer considered justified owing to the risk of severe hematological adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p27)
A laxative that undergoes enterohepatic circulation. It may cause jaundice.
A quaternary ammonium anticholinergic agent with peripheral side effects similar to those of ATROPINE. It is used as an adjunct in the treatment of gastric and duodenal ulcer, and to relieve visceral spasms. The drug has also been used in the form of eye drops for mydriatic effect.
Drugs that stimulate contraction of the myometrium. They are used to induce LABOR, OBSTETRIC at term, to prevent or control postpartum or postabortion hemorrhage, and to assess fetal status in high risk pregnancies. They may also be used alone or with other drugs to induce abortions (ABORTIFACIENTS). Oxytocics used clinically include the neurohypophyseal hormone OXYTOCIN and certain prostaglandins and ergot alkaloids. (From AMA Drug Evaluations, 1994, p1157)
A nonapeptide hormone released from the neurohypophysis (PITUITARY GLAND, POSTERIOR). It differs from VASOPRESSIN by two amino acids at residues 3 and 8. Oxytocin acts on SMOOTH MUSCLE CELLS, such as causing UTERINE CONTRACTIONS and MILK EJECTION.
Infection with nematodes of the superfamily OXYUROIDEA.
The glycine amide of 4-aminobenzoic acid. Its sodium salt is used as a diagnostic aid to measure effective renal plasma flow (ERPF) and excretory capacity.
An analog of para-aminobenzoic acid (PABA) with antitubercular activity. Aminosalicylic acid exerts its bacteriostatic activity against Mycobacterium tuberculosis by competing with PABA for enzymes involved in folate synthesis, thereby suppressing growth and reproduction of M. tuberculosis, eventually leading to cell death.
A hapten capable of eliciting both antibody formation and delayed hypersensitivity when bound to aromatic amino acids, polypeptides or proteins. It is used as an immunologic research tool.
A chlorinated neurotoxic derivative of amphetamine. Although the exact mechanism of action has yet to be fully elucidated, parachloroamphetamine (PCA) neurotoxicity appears to be the result of unrestrained release of both serotonin and dopamine; PCA is used by researchers to selectively kill serotonergic neurons.
A selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine acts pharmacologically to deplete endogenous levels of serotonin.
Amphetamine metabolite with sympathomimetic effects. It is sometimes called alpha-methyltyramine, which may also refer to the meta isomer, gepefrine.
Parahydroxy analog of phenylpropanolamine with properties as a sympathomimetic.
A malignant neoplasm in which there is infiltration of the skin overlying the breast by neoplastic large cells with abundant pale cytoplasm and large nuclei with prominent nucleoli (Paget cells). It is almost always associated with an intraductal or invasive ductal carcinoma of the breast. The clinical features include focal skin reddening, and eczema. Retraction of the nipple may sometimes occur.
A malignant neoplasm in which there is infiltration of the skin by neoplastic large cells with abundant pale cytoplasm and large nuclei with prominent nucleoli (Paget cells). It may affect the anus, penis, scrotum, and vulva.
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.
Chronic pain in the limbs with no clear focal etiology.
Persistent pain that is refractory to some or all forms of treatment.
A sensation of discomfort secondary to surgery.
Palatal myoclonus is characterized by myoclonic (rhythmic involuntary jerky) movements of the soft palate.
A benign or malignant neoplasm that affects the hard palate, soft palate, or uvula.
A clinical manifestation consisting of an unnatural paleness of the skin.
A chronic inflammatory disorder that generally occurs in adulthood and is characterized by sterile pustules intermingled with scaly erythemas, vesicles and hyperkeratosis occurring at distinct sites on the palms and soles. It is thought to be an autoimmune disorder precipitated by several factors, including local infection, and smoking.
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
A rare neoplastic syndrome characterized by obstruction of the thoracic outlet leading to compression of the brachial plexus and vessels within. It is usually caused by a malignant neoplasm in the superior pulmonary sulcus. The most commonly involved neoplasms are non-small cell lung carcinomas. Clinical signs include Horner's syndrome, shoulder pain radiating down the arm in the ulnar distribution followed by edema and atrophy of the affected extremity. Clinical course usually leads to early local invasion of the bony thoracic structures. Prognosis is highly stage-dependent.
A cyst of the pancreas that possess a lining of mucous epithelium.
Extracts prepared from pancreatic tissue that may contain the pancreatic enzymes or other specific uncharacterized factors or proteins with specific activities. PANCREATIN is a specific extract containing digestive enzymes and used to treat pancreatic insufficiency.
Abnormal passage communicating with the PANCREAS.
Peptide hormones secreted into the blood by cells in the ISLETS OF LANGERHANS of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide.
Impaired function of the exocrine pancreas associated with a reduced ability to digest foods because of lack of digestive enzymes.
A benign or malignant neoplasm involving the pancreas.
Cyst-like space not lined by EPITHELIUM and contained within the PANCREAS. Pancreatic pseudocysts account for most of the cystic collections in the pancreas and are often associated with chronic PANCREATITIS.
A mammalian pancreatic extract composed of enzymes with protease, amylase and lipase activities. It is used as a digestant in pancreatic malfunction.
INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis.
A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than CURARE but has less effect on the circulatory system and on histamine release.
The bromide salt form of pancuronium, a synthetic, long-acting ammonio steroid muscle relaxant with curarimimetic, some antimuscarinic and sympathomimetic effects. Pancuronium bromide competitively binds to the nicotinic receptor at the neuromuscular junction, thereby preventing acetylcholine binding and resulting in skeletal muscle relaxation and paralysis.
A finding of low numbers of red and white blood cells and platelets in the peripheral blood.
A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function.
A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.
General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules.
A condition primarily affecting the subcutaneous adipose tissues, showing firm nodules that often resolve with lipoatrophy. There can be overlying changes of discoid lupus erythematosus. A skin biopsy showing lobular panniculitis with typical changes of lupus is needed to rule out other causes of panniculitis, including subcutaneous panniculitis-like T-cell lymphoma.
A form of panniculitis characterized by recurrent episodes of fever accompanied by the eruption of single or multiple erythematous subcutaneous nodules on the lower extremities. They normally resolve, but tend to leave depressions in the skin. The condition is most often seen in women, alone or in association with other disorders.
A disorder characterized by chronic inflammation and fibrosis of the adipose tissues in the peritoneal cavity.
Acute suppurative inflammation of the inner eye with necrosis of the sclera (and sometimes the cornea) and extension of the inflammation into the orbit. Pain may be severe and the globe may rupture. In endophthalmitis the globe does not rupture.
A butyryl-beta-alanine that can also be viewed as pantoic acid complexed with BETA ALANINE. It is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE.
A disorder characterized by inflammation of the entire uvea which includes the iris, ciliary body, and choroid. Causes include systemic infections, sarcoidosis, and cancers.
A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and CHYMOPAPAIN that is used as a topical enzymatic debriding agent. EC 3.4.22.2.
An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels.
Papilledema refers to edema (swelling) of the optic disc secondary to any factor which increases cerebral spinal fluid pressure.
A benign epithelial neoplasm that projects above the surrounding epithelial surface and consists of villous or arborescent outgrowths of fibrovascular stroma.
A rabbit papilloma that is associated with infection by the Shope papilloma virus.
Papillion-Lefevre syndrome is an autosomal recessive disorder characterized by palmoplantar keratoderma, periodontitis, and premature loss of dentition (summary by Lefevre et al., 2001).
Influenza-like febrile viral disease caused by several members of the BUNYAVIRIDAE family and transmitted mostly by the bloodsucking sandfly Phlebotomus papatasii.
Methyl, propyl, butyl, and ethyl esters of p-hydroxybenzoic acid. They have been approved by the FDA as antimicrobial agents for foods and pharmaceuticals. (From Hawley's Condensed Chemical Dictionary, 11th ed, p872)
A mycosis affecting the skin, mucous membranes, lymph nodes, and internal organs. It is caused by Paracoccidioides brasiliensis. It is also called paracoccidioidal granuloma. Superficial resemblance of P. brasiliensis to Blastomyces brasiliensis (BLASTOMYCES) may cause misdiagnosis.
A benign or malignant neoplasm arising from paraganglia located along the sympathetic or parasympathetic nerves. Infrequently, it may arise outside the usual distribution of the sympathetic and parasympathetic paraganglia. Tumors arising from the adrenal gland medulla are called pheochromocytomas. Morphologically, paragangliomas usually display a nesting (Zellballen) growth pattern. There are no reliable morphologic criteria to distinguish between benign and malignant paragangliomas. The only definitive indicator of malignancy is the presence of regional or distant metastases.
A benign or malignant paraganglioma arising from sympathetic or parasympathetic paraganglia outside the adrenal gland.
A parasitic infection caused by trematodes of the Paragonimus genus. Humans are infected from ingestion of raw or undercooked food. It results in chronic lung infection and eosinophilia.
Abnormal formation of the keratinocytes of the epidermis characterized by persistence of nuclei, incomplete formation of keratin, and moistness and swelling of the keratinocytes.
A hypnotic and sedative with anticonvulsant effects. However, because of the hazards associated with its administration, its tendency to react with plastic, and the risks associated with its deterioration, it has largely been superseded by other agents. It is still occasionally used to control status epilepticus resistant to conventional treatment. (From Martindale, The Extra Pharmacopoeia, 30th ed, p608-9)
A motor neuron disease marked by progressive weakness of the muscles innervated by cranial nerves of the lower brain stem. Clinical manifestations include dysarthria, dysphagia, facial weakness, tongue weakness, and fasciculations of the tongue and facial muscles. The adult form of the disease is marked initially by bulbar weakness which progresses to involve motor neurons throughout the neuroaxis. Eventually this condition may become indistinguishable from AMYOTROPHIC LATERAL SCLEROSIS. Fazio-Londe syndrome is an inherited form of this illness which occurs in children and young adults. (Adams et al., Principles of Neurology, 6th ed, p1091; Brain 1992 Dec;115(Pt 6):1889-1900)
A group of genetic neurological disorders caused by mutations in genes involved in the sodium and calcium channels in nerve cells. It is characterized by episodes of muscle paralysis in which the affected muscles become flaccid and the deep tendon reflexes disappear. Between the episodes the affected muscles usually work normally.
An ileus caused by abdominal or pelvic surgery, infections, disorders that affect the muscles and nerves, and medications. Signs and symptoms include those of intestinal obstruction.
A glucocorticoid with the general properties of corticosteroids. It has been used by mouth in the treatment of all conditions in which corticosteroid therapy is indicated except adrenal-deficiency states for which its lack of sodium-retaining properties makes it less suitable than HYDROCORTISONE with supplementary FLUDROCORTISONE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p737)
Inflammation of the parametrium, the connective tissue of the pelvic floor, extending from the subserous coat of the uterus laterally between the layers of the BROAD LIGAMENT.
Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.
A benign or malignant neoplasm that affects the paranasal sinuses. Representative examples of benign neoplasms include Schneiderian papilloma and salivary gland-type adenoma. Representative examples of malignant neoplasms include carcinoma and lymphoma.
A classification for rare disorders of diverse organ systems (endocrine, neuromuscular, gastrointestinal, renal, dermatologic, rheumatologic, hematologic) that are affected by substances secreted by a distant neoplasm but not by the action of the neoplasm itself metastasizing to that organ or tissue. Less than 1 % of neoplasms are associated with these syndromes. An immune-mediated response to neoplasm-elaborated proteins may be the cause of these syndromes. Additionally, their manifestation may signal the presence of an occult neoplasm, potentially at an earlier stage of disease thereby leading to a better clinical outcome. Constitutional signs may include fever, night sweats, anorexia and cachexia. Clinical course is usually progressive. Prognosis is variable depending on the effective treatment of the underlying neoplasm.
A disorder characterized by an enduring pattern of behavior based on the pervasive belief that the motives of others are malevolent and that they should not be trusted.
A progressive chronic inflammatory disease of the central nervous system with the aetiologic agent Human T cell lymphotropic virus type I (HTLV-I), the disease is characterised by unremitting myelopathic symptoms such as spastic paraparesis, bowel and/or bladder dysfunction and sensory changes of the lower limbs.
Disorders that include recurrent, intense sexually arousing fantasies, sexual urges, or behaviors generally involving nonhuman objects, suffering of oneself or partners, or children or other nonconsenting partners. (from DSM-V)
A condition in which the FORESKIN, once retracted, cannot return to its original position. If this condition persists, it can lead to painful constriction of GLANS PENIS, swelling, and impaired blood flow to the penis.
A form of schizophrenia characterized by delusions (of persecution or grandeur or jealousy); symptoms may include anger and anxiety and aloofness and doubts about gender identity; unlike other types of schizophrenia the patients are usually presentable and (if delusions are not acted on) may function in an apparently normal manner.
Complete paralysis of the lower half of the body including both legs, often caused by damage to the spinal cord.
A group of related diseases characterized by an unbalanced or disproportionate proliferation of immunoglobulin-producing cells, usually from a single clone. These cells frequently secrete a structurally homogeneous immunoglobulin (M-component) and/or an abnormal immunoglobulin.
An inflammatory skin disorder of unknown etiology characterized by papules and plaques or scaly patches resembling psoriasis.
Infections or infestations with PARASITES. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure.
A group of sleep disorders causing disruption of sleep. Representative examples include nightmare disorders, sleep terror disorders, sleepwalking, and restless leg syndrome.
Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.
Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here.
An abnormality of the parathyroid gland.
A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.
A benign or malignant neoplasm affecting the parathyroid glands.
A chronic GASTROENTERITIS in RUMINANTS caused by MYCOBACTERIUM AVIUM SUBSPECIES PARATUBERCULOSIS.
A condition resembling typhoid fever that is caused by infection by Salmonella enterica serovar Parathyphi.
Abnormal cutaneous sensations of tingling, numbness, pressure, cold, and warmth that an individual experiences without the presence of a stimulus. It results from functional disturbances of sensory neurons. Causes include peripheral vascular disease, peripheral neuropathy, and nerve damage.
A monoamine oxidase (MAO) inhibitor with antidepressant activity. Pargyline selectively inhibits MAO type B, an enzyme catalyzing the oxidative deamination and inactivation of certain catecholamines, such as norepinephrine and dopamine, within the presynaptic nerve terminals. By inhibiting the metabolism of these biogenic amines in the brain, pargyline increases their concentration and binding to postsynaptic receptors. Increased receptor stimulation may cause downregulation of central receptors which may attribute to pargyline's antidepressant effect.
The number of offspring a female has borne. It is contrasted with GRAVIDITY, which refers to the number of pregnancies, regardless of outcome.
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Parkinsonism following encephalitis, historically seen as a sequella of encephalitis lethargica (Von Economo Encephalitis). The early age of onset, the rapid progression of symptoms followed by stabilization, and the presence of a variety of other neurological disorders (e.g., sociopathic behavior; TICS; MUSCLE SPASMS; oculogyric crises; hyperphagia; and bizarre movements) distinguish this condition from primary PARKINSON DISEASE. Pathologic features include neuronal loss and gliosis concentrated in the MESENCEPHALON; SUBTHALAMUS; and HYPOTHALAMUS. (From Adams et al., Principles of Neurology, 6th ed, p754)
A condition with a clinical picture similar to that of Parkinson disease, but which is caused by external factors, including medication.
An acute or chronic infection of the soft tissues around the nail. Symptoms include pain, tenderness, erythema, and swelling around the nail. Acute infection results from minor trauma to the fingertip and Staphylococcus aureus is usually the causative agent. Chronic infection is usually caused by Candida albicans.
A benign or malignant neoplasm that affects the parotid gland. Representative examples of benign neoplasms include Warthin tumor, monomorphic adenoma, and pleomorphic adenoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma.
A cyst (CYSTS) near the OVARY, derived from anomalies of the FALLOPIAN TUBES or the BROAD LIGAMENT. The paramesonephric type consists of ciliated cells similar to the oviduct epithelium. The mesonephric type consisted of an epithelium with minimally surface structures. They can be found on the thin oviduct (paratubal cysts) or near its fimbriated end (hydatid of Morgagni).
A disorder characterized by an electrocardiographic finding of episodic atrial tachycardia with abrupt onset and termination.
An episodic form of supraventricular tachycardia with abrupt onset and termination.
An episodic form of ventricular tachycardia, with abrupt onset and termination.
An inflammatory disorder of the cilliary body in the uvea that affects healthy, younger individuals who are often asymptomatic. It has a long clinical course with relapses and remissions. Symptoms include mildly decreased vision and floaters. It may be associated with autoimmune disorders.
A disease of pregnant and lactating cows and ewes leading to generalized paresis and death. The disease, which is characterized by hypocalcemia, occurs at or shortly after parturition in cows and within weeks before or after parturition in ewes.
A disorder characterized by a pattern of indirect expression of hostility, including negativistic attitudes and passive resistance to demands for adequate performance in social and occupational situations.
Infections with bacteria of the genus PASTEURELLA.
A biologic function or a process having an abnormal or deleterious effect at the subcellular, cellular, multicellular, or organismal level.
Pathologic gambling is defined as a chronic and progressive failure to resist impulses to gamble accompanied by gambling behavior that compromises or damages personal, family, or vocational pursuits. The prevalence of pathologic gambling in the adult American population is estimated to be between 1 and 3% (review by Eisen et al., 1998). Comings et al. (2001) noted that some form of gambling is legal in all but 2 states in the U.S., and gambling on the Internet is available to anyone with a computer regardless of the local laws. They stated that as access to gambling has increased, there has been a corresponding increase in the frequency of addiction to gambling, known as pathologic gambling.
High molecular weight polysaccharides present in the cell walls of all plants. Pectins cement cell walls together. They are used as emulsifiers and stabilizers in the food industry. They have been tried for a variety of therapeutic uses including as antidiarrheals, where they are now generally considered ineffective, and in the treatment of hypercholesterolemia.
A contagious infestation of parasitic insects found on the head (Pediculus humanus capitis), body (Pediculus humanus corporis), or pubic area (Pthirus pubis) that typically cause itching and rash.
Infestation of the pubic hair by the pthirus pubis parasite which results in mild to intense itching and macular lesions. The parasite, also known as crab lice, is transmitted through skin to skin contact with an infected person or through direct contact with infested objects.
A disorder characterized by recurrent sexual urges, fantasies, or behaviors involving sexual activity with a prepubescent child or children.
An autosomal dominant inherited condition caused by mutations in the lamin B receptor gene. It is characterized by defects in the neutrophil lobulation, resulting in the presence of dumbbell-shaped neutrophils with bilobed nuclei in the peripheral blood smear.
A vascular disease of the LIVER characterized by the occurrence of multiple blood-filled CYSTS or cavities. The cysts are lined with ENDOTHELIAL CELLS; the cavities lined with hepatic parenchymal cells (HEPATOCYTES). Peliosis hepatis has been associated with use of anabolic steroids (ANABOLIC AGENTS) and certain drugs.
A disease due to deficiency of NIACIN, a B-complex vitamin, or its precursor TRYPTOPHAN. It is characterized by scaly DERMATITIS which is often associated with DIARRHEA and DEMENTIA (the three D's).
An abscess that is located in the pelvic cavity.
Infection involving the tissues or organs in the PELVIS.
Pain in the pelvic region of genital and non-genital origin.
A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children.
A chronic autoimmune disorder characterized by the development of blisters and ulcers in mucous membranes. It affects most often the gums, eyelids and genital mucosa sites.
A chronic and relatively benign subepidermal blistering disease usually of the elderly and without histopathologic acantholysis.
A blistering skin disorder. Morphologically it is characterized by acantholysis and intraepidermal blister formation.
An autoimmune blistering disorder. It is characterized by the presence of painful blisters and erosions in the skin and mucous membranes.
A nicotinic antagonist most commonly used as an experimental tool. It has been used as a ganglionic blocker in the treatment of hypertension but has largely been supplanted for that purpose by more specific drugs.
A lipophilic, nonselective beta-adrenergic receptor antagonist with anti-anginal and antihypertensive activities. Penbutolol competitively binds to and blocks beta-1 adrenergic receptors in the heart, thereby decreasing cardiac contractility and rate. This leads to a reduction in cardiac output and lowers blood pressure. In addition, penbutolol prevents the release of renin, a hormone secreted by the kidneys that causes constriction of blood vessels.
One of the long-acting ANTIPSYCHOTIC AGENTS used for maintenance or long-term therapy of SCHIZOPHRENIA and other PSYCHOTIC DISORDERS.
3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.
A non-neoplastic or neoplastic disorder that affects the penis. Representative examples of non-neoplastic disorders include phimosis, balanitis, and hypospadias. Representative examples of neoplastic disorders include hemangioma, penile intraepithelial neoplasia, and penile carcinoma.
A condition characterized by hardening of the PENIS due to the formation of fibrous plaques on the dorsolateral aspect of the PENIS, usually involving the membrane (tunica albuginea) surrounding the erectile tissue (corpus cavernosum penis). This may eventually cause a painful deformity of the shaft or constriction of the urethra, or both.
A benign, borderline, or malignant neoplasm that affects the penis. Representative examples include penile hemangioma, penile intraepithelial neoplasia, and penile carcinoma.
A vasodilator with general properties similar to NITROGLYCERIN but with a more prolonged duration of action. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1025)
A synthetic pentapeptide that has effects like gastrin when given parenterally. It stimulates the secretion of gastric acid, pepsin, and intrinsic factor, and has been used as a diagnostic aid.
A synthetic derivative of amidine with antiprotozoal and antifungal activities. Although the precise mode of action of pentamidine is unclear, it appears to interact directly with the pathogen genome by binding to AT-rich regions of duplex DNA and the minor groove of DNA, thereby interfering with DNA replication. (NCI04)
A synthetic amidine derivative, Pentamidine Isethionate is an antiprotozoal and antifungal agent that appears to interact with the minor groove of AT-rich DNA regions of the pathogen genome, interfering with DNA replication and function. It is effective in the treatment of trypanosomiasis, leishmaniasis, some fungal infections, and Pneumocystis carinii pneumonia in HIV-infected patients. (NCI04)
The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)
A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236)
A nicotinic antagonist that has been used as a ganglionic blocking agent in hypertension.
A sulfated pentosyl polysaccharide with heparin-like properties.
An oxidative decarboxylation process that converts GLUCOSE-6-PHOSPHATE to D-ribose-5-phosphate via 6-phosphogluconate. The pentose product is used in the biosynthesis of NUCLEIC ACIDS. The generated energy is stored in the form of NADPH. This pathway is prominent in tissues which are active in the synthesis of FATTY ACIDS and STEROIDS.
Pentavalent antimony (Sb) in differential complex formation with gluconic acid with leishmanicidal and potential antineoplastic activities. The Sb moiety of sodium stibogluconate (SSG) may inhibit protein tyrosine phosphorylases (PTPases) by covalently modifying sulfhydryl groups in PTPase cysteine residues, resulting in specific inactivation of SH2 domain-containing tyrosine phosphatases-1 and -2 (SHP-1 and SHP-2), PTPases which negatively regulate interferon (IFN) signaling; enhancement of IFN-induced Stat1 tyrosine phosphorylation; and induction of cellular protein tyrosine phosphorylation. SSG in combination with IFN-alpha may synergize to overcome tumor cell resistance to IFN-alpha-mediated apoptosis.
A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.
5-Hydroxymethyl-6-methyl- 2,4-(1H,3H)-pyrimidinedione. Uracil derivative used in combination with toxic antibiotics to lessen their toxicity; also to stimulate leukopoiesis and immunity. Synonyms: pentoksil; hydroxymethylmethyluracil.
A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility.
Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice.
A mucosal erosion that occurs in the esophagus, stomach or duodenum. Symptoms can include abdominal pain, nausea and vomiting, and bleeding.
Bleeding from a PEPTIC ULCER that can be located in any segment of the GASTROINTESTINAL TRACT.
Penetration of a PEPTIC ULCER through the wall of DUODENUM or STOMACH allowing the leakage of luminal contents into the PERITONEAL CAVITY.
A mixture of six synthetic oligopeptides in which the peptides are conjugated to metamelphalan, with alkylating and potential antineoplastic activity. Peptichemio causes crosslinking of DNA, thereby preventing DNA replication and eventually cellular proliferation.
A class of enzymes that catalyze the hydrolysis of peptide bonds in the interior of a polypeptide chain or protein molecule.
N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)-L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor.
A compound of two or more amino acids where the alpha carboxyl group of one is bound to the alpha amino group of another.
A phenothiazine antipsychotic with actions and uses similar to those of CHLORPROMAZINE. Extrapyramidal symptoms may be more common than other side effects.
Cognitive disorders characterized by an impaired ability to perceive the nature of objects or concepts through use of the sense organs. These include spatial neglect syndromes, where an individual does not attend to visual, auditory, or sensory stimuli presented from one side of the body.
A long-acting dopamine agonist which has been used to treat PARKINSON DISEASE and HYPERPROLACTINEMIA but withdrawn from some markets due to potential for HEART VALVE DISEASES.
A semi-synthetic ergot derivative and a dopamine agonist with antiparkinson property. Pergolide mesylate binds to and activates dopamine receptor subtypes D1 and D2, resulting in prolactin secretion inhibition, transient increase in serum concentration of growth hormone, and decrease in serum concentration of luteinizing hormone. Direct stimulation of postsynaptic dopamine receptors in the nigrostriatal system, may account for this agent's antiparkinson activity.
2-(2,2-Dicyclohexylethyl)piperidine. Coronary vasodilator used especially for angina of effort. It may cause neuropathy and hepatitis.
An abscess that develops in the soft tissues surrounding the anal canal. Causes include bacterial and fungal infections, malignancies that involve the perianal region, and Crohn disease.
Acute or chronic inflammation of tissues surrounding the apical portion of a tooth, associated with the collection of pus, resulting from infection following pulp infection through a carious lesion or as a result of an injury causing pulp necrosis. (Dorland, 27th ed)
Diseases of the PERIAPICAL TISSUE surrounding the root of the tooth, which is distinguished from DENTAL PULP DISEASES inside the TOOTH ROOT.
Chronic nonsuppurative inflammation of periapical tissue resulting from irritation following pulp disease or endodontic treatment.
Inflammation of the PERIAPICAL TISSUE. It includes general, unspecified, or acute nonsuppurative inflammation. Chronic nonsuppurative inflammation is PERIAPICAL GRANULOMA. Suppurative inflammation is PERIAPICAL ABSCESS.
Adenosine deaminase 2 (ADA2) deficiency is a disorder characterized by abnormal inflammation of various tissues. Signs and symptoms can begin anytime from early childhood to adulthood. The severity of the disorder also varies, even among affected individuals in the same family.Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, ADA2 deficiency causes abnormal, unprovoked inflammation that can damage the body's tissues and organs, particularly blood vessels. (Inflammation of blood vessels is known as vasculitis.) Other tissues affected by abnormal inflammation can include the skin, gastrointestinal system, liver, kidneys, and nervous system. Depending on the severity and location of the inflammation, the disorder can cause disability or be life-threatening.Signs and symptoms that can occur with ADA2 deficiency include fevers that are intermittent, meaning they come and go; areas of net-like, mottled skin discoloration called livedo racemosa; an enlarged liver and spleen (hepatosplenomegaly); and recurrent strokes affecting structures deep in the brain that can start in the first few years of life. In some people, ADA2 deficiency causes additional immune system abnormalities that increase the risk of bacterial and viral infections.ADA2 deficiency is sometimes described as a form of polyarteritis nodosa (PAN), a disorder that causes inflammation of blood vessels throughout the body (systemic vasculitis). However, not all researchers classify ADA2 deficiency as a type of PAN.
Inflammation of the tissues around a joint. (Dorland, 27th ed)
Accumulation of fluid within the pericardium.
An inflammatory process affecting the pericardium.
A heart disorder in which the pericardial sac becomes thickened and fibrotic, tightening the myocardium and impeding the normal myocardial function.
INFLAMMATION of the sac surrounding the heart (PERICARDIUM) due to MYCOBACTERIUM TUBERCULOSIS infection. Pericarditis can lead to swelling (PERICARDIAL EFFUSION), compression of the heart (CARDIAC TAMPONADE), and preventing normal beating of the heart.
Inflammation of the tissue surrounding the biliary ducts.
Inflammation of the gingiva surrounding the crown of a tooth.
Inflammation of the connective and adipose tissues surrounding the KIDNEY.
Familial Mediterranean fever (FMF) is divided into two phenotypes: type 1 and type 2. FMF type 1 is characterized by recurrent short episodes of inflammation and serositis including fever, peritonitis, synovitis, pleuritis, and, rarely, pericarditis and meningitis. The symptoms and severity vary among affected individuals, sometimes even among members of the same family. Amyloidosis, which can lead to renal failure, is the most severe complication, if untreated. FMF type 2 is characterized by amyloidosis as the first clinical manifestation of FMF in an otherwise asymptomatic individual.
An acute purulent bacterial infection that arises from the tissues that surround and support the teeth.
An inflammatory process of the gingival tissues and/or periodontal membrane of the teeth, resulting in an abnormally deep gingival sulcus, possibly producing periodontal pockets and loss of alveolar bone support.
An abnormal deepening of a gingival sulcus associated with destruction of the supporting periodontal tissue.
An acute or chronic inflammatory process that affects the tissues that surround and support the teeth.
Inflammation and loss of PERIODONTIUM that is characterized by rapid attachment loss and bone destruction in the presence of little local factors such as DENTAL PLAQUE and DENTAL CALCULUS. This highly destructive form of periodontitis often occurs in young people and was called early-onset periodontitis, but this disease also appears in old people.
A disorder affecting the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.
A benign or malignant neoplasm (tumour) of the peripheral nervous system.
Periphlebitis is inflammation of the outer coat of a vein or of tissues surrounding the vein.
A non-neoplastic or neoplastic disorder that affects the peritoneal cavity. Representative examples of non-neoplastic disorders include peritonitis and panniculitis. Representative examples of neoplastic disorders include adenomatoid tumor, primary peritoneal carcinoma, metastatic carcinoma to the peritoneum, and malignant mesothelioma.
Persistent or recurring accumulation of fluid in the peritoneal cavity.
A benign or malignant neoplasm that affects the peritoneal cavity. Representative examples of benign neoplasms include adenomatoid tumor and disseminated peritoneal leiomyomatosis. Representative examples of malignant neoplasms include primary peritoneal carcinoma, metastatic carcinoma to the peritoneum, and malignant mesothelioma.
INFLAMMATION of the PERITONEUM lining the ABDOMINAL CAVITY as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the PERITONEAL CAVITY via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the ABDOMINAL CAVITY itself through RUPTURE or ABSCESS of intra-abdominal organs.
An abscess that develops in the space surrounding one or both palatine tonsils.
A phenothiazine derivative and a dopamine antagonist with antiemetic and antipsychotic properties. Perphenazine blocks postsynaptic dopamine 2(D2) receptors in the mesolimbic and medullary chemoreceptor trigger zone (CTZ), thereby preventing the excess of dopamine in the brain. This leads to reduction in psychotic symptoms, such as hallucinations and delusions. Perphenazine appears to exert its antiemetic activity by blocking the dopamine and histamine-1 receptor in the CTZ thereby relieving nausea and vomiting in the brain. In addition, perphenazine binds to alpha-adrenergic receptors.
Congenital alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is characterized histologically by failure of formation and ingrowth of alveolar capillaries that then do not make contact with alveolar epithelium, medial muscular thickening of small pulmonary arterioles with muscularization of the intraacinar arterioles, thickened alveolar walls, and anomalously situated pulmonary veins running alongside pulmonary arterioles and sharing the same adventitial sheath. Less common features include a reduced number of alveoli and a patchy distribution of the histopathologic changes. The disorder is associated with persistent pulmonary hypertension of the neonate and shows varying degrees of lability and severity (Boggs et al., 1994). Affected infants present with respiratory distress resulting from pulmonary hypertension in the early postnatal period, and the disease is uniformly fatal within the newborn period (Vassal et al., 1998). Additional features of ACDMPV include multiple congenital anomalies affecting the cardiovascular, gastrointestinal, genitourinary, and musculoskeletal systems, as well as disruption of the normal right-left asymmetry of intrathoracic or intraabdominal organs (Sen et al., 2004).
A congenital defect in the atrial septum at the level of the atrioventricular valves, resulting in abnormalities in the mitral and/or tricuspid valve; this defect is most commonly seen in those with Trisomy 21.
The individual's experience of a sense of fulfillment of a need or want and the quality or state of being satisfied.
A diverse category of psychiatric disorders characterized by behavior that deviates markedly from the expectations of the individual's culture; this pattern of deviation is pervasive and inflexible and is stable over time. The behavioral pattern negatively interferes with relationships and work.
A suspension of killed Bordetella pertussis organisms, used for immunization against pertussis (WHOOPING COUGH). It is generally used in a mixture with diphtheria and tetanus toxoids (DTP). There is an acellular pertussis vaccine prepared from the purified antigenic components of Bordetella pertussis, which causes fewer adverse reactions than whole-cell vaccine and, like the whole-cell vaccine, is generally used in a mixture with diphtheria and tetanus toxoids. (From Dorland, 28th ed)
A group of small reddish or purplish spots in skin or mucous membrane as a result of localized hemorrhage.
A colloidal system of semisolid hydrocarbons obtained from PETROLEUM. It is used as an ointment base, topical protectant, and lubricant.
Peutz-Jeghers syndrome (PJS) is an autosomal dominant condition characterized by the association of gastrointestinal polyposis, mucocutaneous pigmentation, and cancer predisposition. Peutz-Jeghers-type hamartomatous polyps are most common in the small intestine (in order of prevalence: in the jejunum, ileum, and duodenum) but can also occur in the stomach, large bowel, and extraintestinal sites including the renal pelvis, bronchus, gall bladder, nasal passages, urinary bladder, and ureters. Gastrointestinal polyps can result in chronic bleeding and anemia and also cause recurrent obstruction and intussusception requiring repeated laparotomy and bowel resection. Mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are common. The macules may fade in puberty and adulthood. Individuals with Peutz-Jeghers syndrome are at increased risk for a wide variety of epithelial malignancies (colorectal, gastric, pancreatic, breast, and ovarian cancers). Females are at risk for sex cord tumors with annular tubules (SCTAT), a benign neoplasm of the ovaries, and adenoma malignum of the cervix, a rare aggressive cancer. Males occasionally develop large calcifying Sertoli cell tumors (LCST) of the testes, which secrete estrogen and can lead to gynecomastia, advanced skeletal age, and ultimately short stature, if untreated.
Disorders in which phagocytic cells cannot kill ingested bacteria; characterized by frequent recurring infection with formulation of granulomas.
Persistent postural and motor experiences of the limb after physical loss.
A non-neoplastic or neoplastic disorder that affects the pharynx. Representative examples include pharyngitis and carcinoma.
A benign or malignant neoplasm that affects the nasopharynx, oropharynx, or hypopharynx.
Inflammation (due to infection or irritation) of the pharynx.
A condition characterized by fever, conjunctivitis, and pharyngitis resulting from infection by adenovirus.
POLYCYCLIC AROMATIC HYDROCARBONS composed of three fused BENZENE rings.
An opioid analgesic with actions and uses similar to MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1095)
A local anesthetic that has been used in urinary tract disorders. Its use is limited by problems with toxicity (primarily blood disorders) and potential carcinogenicity.
A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.
The misuse of phencyclidine with associated psychological symptoms and impairment in social or occupational functioning.
One of the MONOAMINE OXIDASE INHIBITORS used to treat DEPRESSION; PHOBIC DISORDERS; and PANIC.
A hydrazine derivative and a potent non-selective monoamine oxidase (MAO) inhibitor with anxiolytic and antidepressant properties. Phenelzine sulfate irreversibly binds to MAO, thereby blocking the oxidative deamination of monoamines resulting in an increased concentration of biogenic amines and a concurrent decrease in catabolism of monoamine neurotransmitters, norepinephrine and serotonin, in the brain. In addition, through its primary metabolite phenylethylidenehyrazine (PEH), phenelzine causes elevated GABA levels in the caudate-putamen and nucleus accumbens thereby exerting its anxiolytic effects.
An antimicrobial, antiseptic, and disinfectant that is used also as an aromatic essence and preservative in pharmaceutics and perfumery.
A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)
A biguanide hypoglycemic agent with actions and uses similar to those of METFORMIN. Although it is generally considered to be associated with an unacceptably high incidence of lactic acidosis, often fatal, it is still available in some countries. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)
An indandione that has been used as an anticoagulant. Phenindione has actions similar to WARFARIN, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234)
One of the HISTAMINE H1 ANTAGONISTS with little sedative action. It is used in treatment of hay fever, rhinitis, allergic dermatoses, and pruritus.
A sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to DEXTROAMPHETAMINE.
A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.
A family of 3,3-bis(p-hydroxyphenyl)phthalides. They are used as CATHARTICS, indicators, and COLORING AGENTS.
Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
Red dye, pH indicator, and diagnostic aid for determination of renal function. It is used also for studies of the gastrointestinal and other systems.
A narcotic analgesic partly metabolized to meperidine in the liver. It is similar to morphine in action and used for neuroleptanalgesia, usually with droperidol.
A class of agents exhibiting antiemetic, antipsychotic, antihistaminic, and anticholinergic activities. Phenothiazines antagonize the dopamine D2-receptor in the chemoreceptor trigger zone (CTZ) of the brain, potentially preventing chemotherapy-induced emesis. In addition, these agents have peripherally or centrally antagonistic activity against alpha adrenergic, serotonergic, histaminic, and muscarinic receptors. (NCI)
Compounds containing dibenzo-1,4-thiazine. Some of them are neuroactive.
A synthetic, dibenzamine alpha adrenergic antagonist with antihypertensive and vasodilatory properties. Phenoxybenzamine non-selectively and irreversibly blocks the postsynaptic alpha-adrenergic receptor in smooth muscle, thereby preventing vasoconstriction, relieving vasospasms, and decreasing peripheral resistance. Reflex tachycardia may occur and may be enhanced by blockade of alpha-2 receptors which enhances norepinephrine release. Phenoxybenzamine is reasonably anticipated to be a human carcinogen.
An orally available, long-acting derivative of coumarin with anticoagulant activity. Upon administration, phenprocoumon inhibits the vitamin K epoxide reductase enzyme; inhibition of this enzyme prevents the formation of the reduced, active form of vitamin K (vitamin KH2), which is essential for the carboxylation of glutamate residues of vitamin K-dependent proteins. This prevents the activation of vitamin K-dependent coagulation factors II, VII, IX, and X and the anticoagulant proteins C and S, which abrogates both thrombin production and thrombus formation.
A central nervous system stimulant and sympathomimetic with actions and uses similar to those of DEXTROAMPHETAMINE. It has been used most frequently in the treatment of obesity.
A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of RAYNAUD DISEASE and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease.
An essential aromatic amino acid in humans (provided by food), Phenylalanine plays a key role in the biosynthesis of other amino acids and is important in the structure and function of many proteins and enzymes. Phenylalanine is converted to tyrosine, used in the biosynthesis of dopamine and norepinephrine neurotransmitters. The L-form of Phenylalanine is incorporated into proteins, while the D-form acts as a painkiller. Absorption of ultraviolet radiation by Phenylalanine is used to quantify protein amounts. (NCI04)
An enzyme that catalyzes the deamination of PHENYLALANINE to form trans-cinnamate and ammonia.
A butyl-diphenyl-pyrazolidinedione that has anti-inflammatory, antipyretic, and analgesic activities. It has been used in ANKYLOSING SPONDYLITIS; RHEUMATOID ARTHRITIS; and REACTIVE ARTHRITIS.
Aniline compounds that contain two amino groups. They are used as a precursor in the synthesis of HETEROCYCLIC COMPOUNDS and POLYMERS. p-Phenylenediamine is used in the manufacture of HAIR DYES and is an ALLERGEN.
A direct-acting sympathomimetic amine chemically related to adrenaline and ephedrine with potent vasoconstrictor property. Phenylephrine is a post-synaptic alpha-adrenergic receptor agonist that causes vasoconstriction, increases systolic/diastolic pressures, reflex bradycardia, and stroke output.
The hydrochloride salt form of phenylephrine, a direct-acting sympathomimetic amine chemically related to adrenaline and ephedrine with potent vasoconstrictor property. Phenylephrine is a post-synaptic alpha-adrenergic receptor agonist that causes vasoconstriction, increases systolic/diastolic pressures, reflex bradycardia, and stroke output.
A reagent that is highly selective for the modification of arginyl residues. It is used to selectively inhibit various enzymes and acts as an energy transfer inhibitor in photophosphorylation.
diazo derivative of aniline used as a reagent for sugars, ketones and aldehydes.
N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.
Phenylalanine hydroxylase (PAH) deficiency results in intolerance to the dietary intake of the essential amino acid phenylalanine and produces a spectrum of disorders. The risk of adverse outcome varies based on the degree of PAH deficiency. Without effective therapy, most individuals with severe PAH deficiency, known as classic PKU, develop profound and irreversible intellectual disability. Affected individuals on an unrestricted diet who have phenylalanine levels above normal but below 1200 µmol/L (20 mg/dL) are at much lower risk for impaired cognitive development in the absence of treatment.
An enzyme inhibitor that inactivates IRC-50 arvin, subtilisin, and the fatty acid synthetase complex.
A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.
A hydantoin derivative and a non-sedative antiepileptic agent with anticonvulsant activity. Phenytoin potentially acts by promoting sodium efflux from neurons located in the motor cortex reducing post-tetanic potentiation at synapses. The reduction of potentiation prevents cortical seizure foci spreading to adjacent areas, stabilizing the threshold against hyperexcitability. In addition, this agent appears to reduce sensitivity of muscle spindles to stretch causing muscle relaxation.
Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues distributed along the paravertebral axis from the base of the skull to the pelvis) and pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas cause catecholamine excess; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base and neck (referred to as head and neck PGL [HNPGL]) and sometimes in the upper mediastinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically lead to catecholamine excess. Symptoms of PGL/PCC result from either mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for developing metastatic disease is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas.
A translocation between chromosomes 9 and 22. It is the hallmark for chronic myelogenous leukemia (CML).
A condition in which the FORESKIN cannot be retracted to reveal the GLANS PENIS. It is due to tightness or narrowing of the foreskin opening.
Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (THROMBOPHLEBITIS).
Inflammation that is characterized by swollen, pale, and painful limb. It is usually caused by DEEP VEIN THROMBOSIS in a FEMORAL VEIN, following PARTURITION or an illness. This condition is also called milk leg or white leg.
Purulent inflammation of the cellular or areolar tissue.
An overwhelming, irrational, and persistent fear of attending school.
An anxiety disorder characterized by an intense, irrational fear of one or more social or performance situations in which the individual believes that he or she will be scrutinized by others. Exposure to social situations immediately provokes an anxiety response. In adults, the social phobia is recognized as excessive or unreasonable.
A congenital malformation in which the upper portion of a limb is either shortened or absent.
A complex mixture of PHOSPHOLIPIDS; GLYCOLIPIDS; and TRIGLYCERIDES; with substantial amounts of PHOSPHATIDYLCHOLINES; PHOSPHATIDYLETHANOLAMINES; and PHOSPHATIDYLINOSITOLS, which are sometimes loosely termed as 1,2-diacyl-3-phosphocholines. Lecithin is a component of the CELL MEMBRANE and commercially extracted from SOYBEANS and EGG YOLK. The emulsifying and surfactant properties are useful in FOOD ADDITIVES and for forming organogels (GELS).
An enzyme that catalyzes the formation of phosphatidylserine and CMP from CDPdiglyceride plus serine. EC 2.7.8.8.
An endogenous substance found mainly in skeletal muscle of vertebrates. It has been tried in the treatment of cardiac disorders and has been added to cardioplegic solutions. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1996)
Any substance that inhibits phosphodiesterase, an enzyme that catalyzes the breaking of a phosphodiester bond. Usually, this refers to cyclic nucleotide phosphodiesterase, an enzyme that breaks the phosphodiester bond in the second messenger molecules cAMP and cGMP. Inhibition of cyclic nucleotide phosphodiesterase can be used to affect vasodilation.
A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent.
A group of nitrogen mustard compounds which are substituted with a phosphoramide group or its derivatives. They are usually cytotoxic and used as antineoplastic agents.
A colorless, odorless phosphorus-containing inorganic acid. Phosphoric acid is a sequestering agent which binds many divalent cations, including Fe++, Cu++, Ca++, and Mg++. Phosphoric acid is used in dentistry and orthodontics as an etching solution, to clean and roughen the surfaces of teeth where dental appliances or fillings will be placed. In addition, phosphoric acid is a constituent in bone and teeth, and plays a role in many metabolic processes.
A metabolic disorder that affects the phosphate homeostasis.
The creation of a phosphate derivative of an organic molecule. This is usually achieved by transferring a phosphate group from ATP via the action of a kinase.
Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction.
A red, edematous rash that occurs on areas of the skin with recent exposure to sunlight.
Chemical bond cleavage reactions resulting from absorption of radiant energy.
The use of light to convert ADP to ATP without the concomitant reduction of dioxygen to water as occurs during OXIDATIVE PHOSPHORYLATION in MITOCHONDRIA.
An abnormal inflammatory skin condition resulting from exposure to ultraviolet light, most commonly sunlight. May result from phototoxic or photoallergic reactions or both.
A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.
An enzyme that catalyzes the conversion of myo-inositol hexakisphosphate and water to 1L-myo-inositol 1,2,3,4,5-pentakisphosphate and orthophosphate. EC 3.1.3.26.
Complexing agent for removal of traces of heavy metal ions. It acts also as a hypocalcemic agent.
A family of phylloquinones that contains a ring of 2-methyl-1,4-naphthoquinone and an isoprenoid side chain. Members of this group of vitamin K 1 have only one double bond on the proximal isoprene unit. Rich sources of vitamin K 1 include green plants, algae, and photosynthetic bacteria. Vitamin K1 has antihemorrhagic and prothrombogenic activity.
A class of organic compounds known as sterols or STEROIDS derived from plants.
An appetite for and the persistent ingestion of non-food substances such as clay. In order to diagnose pica, this behavior must have persisted over a period of at least one month.
A lyophilized formulation containing cultures of a low-virulent strain of Streptococcus pyogenes, treated and killed with pencillin G, with potential sclerosing, immunostimulating and antineoplastic activity. Besides from picibanil's direct damaging effect as a sclerosing agent, it seems to have multiple effects on the immune system as a non-specific immunostimulant. Picibanil activates the host immune system by stimulating the activity of natural killer cells, macrophages and lymphocytes, and by enhancing the production of several key immune mediators, including interleukins and tumor necrosis factor.
HYPOVENTILATION syndrome in very obese persons with excessive ADIPOSE TISSUE around the ABDOMEN and DIAPHRAGM. It is characterized by diminished to absent ventilatory chemoresponsiveness; chronic HYPOXIA; HYPERCAPNIA; POLYCYTHEMIA; and long periods of sleep during day and night (HYPERSOMNOLENCE). It is a condition often related to OBSTRUCTIVE SLEEP APNEA but can occur separately.
Virus diseases caused by the PICORNAVIRIDAE.
A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.
Either of two diseases resulting from fungal infection of the hair shafts. Black piedra occurs mainly in and on the hairs of the scalp and is caused by Piedraia hortae; white piedra occurs in and on the hairs of the scalp, beard, moustache and genital areas and is caused by Trichosporon species.
Pierre Robin sequence is a craniofacial anomaly comprising mandibular hypoplasia, cleft secondary palate, and glossoptosis leading to life-threatening obstructive apnea and feeding difficulaties during the neonatal period (summary by Tan et al., 2013).
A natural alkaloid extracted from plants of the genus Pilocarpus with cholinergic agonist activity. As a cholinergic parasympathomimetic agent, pilocarpine predominantly binds to muscarinic receptors, thereby inducing exocrine gland secretion and stimulating smooth muscle in the bronchi, urinary tract, biliary tract, and intestinal tract. When applied topically to eyes, this agent stimulates the sphincter pupillae to contract, resulting in miosis; stimulates the ciliary muscle to contract, resulting in spasm of accommodation; and may cause a transitory rise in intraocular pressure followed by a more persistent fall due to opening of the trabecular meshwork and an increase in the outflow of aqueous humor.
A hair-containing cyst or sinus, occurring chiefly in the coccygeal region.
A diphenylbutylpiperidine derivative and a dopamine antagonist with antipsychotic property. Pimozide selectively inhibits type 2 dopaminergic receptors in the central nervous system (CNS), thereby decreasing dopamine neurotransmission and reducing the occurrence of motor and vocal tics and delusions of parasitosis. In addition, this agent antagonizes alpha-adrenergic and 5-HT2 receptors.
A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)
A neoplasm arising from the pineocyte, a cell with photosensory and neuroendocrine functions. It may be composed of mature elements or primitive, immature cells. The cellular composition determines the biological behavior and clinical outcome. Three types are recognized: pineoblastoma, pineocytoma, and pineal parenchymal tumor of intermediate differentiation (Adapted from WHO.)
An endemic bacterial infection caused by Treponema carateum. It is manifested with chronic cutaneous lesions. The early lesions consist of papules and erythematous plaques. The late lesions consist of hypochromic, achromic, hyperpigmented and atrophic lesions. The late skin lesions may cause destruction of bones and cartilage and produce disfiguring changes.
A pyridopyrimidine antibiotic derivative of piromidic acid with activity against gram-negative bacteria, as well as some gram-positive bacteria. Pipemidic acid exhibits greater activity than piromidic acid or nalidixic acid and shows moderate activity against bacteria that are resistant to piromidic acid and nalidixic acid.
An anti-nematodal agent effective against the intestinal nematodes ASCARIS LUMBRICOIDES (roundworm) and ENTEROBIUS VERMICULARIS (pinworm, threadworm). It produces a neuromuscular block leading to flaccid muscle paralysis in susceptible worms, which are then dislodged from the gut and expelled in feces.
A synthetic derivative of benzodioxole and used as an insecticide synergist, Piperonyl Butoxide enhances the active properties of pyrethrin, pyrethroid, rotenone, and carbamate pesticide ingredients by inhibiting insect microsomal enzyme detoxification activity. It is toxic and suspected of causing anorexia, carcinogenesis, convulsions, and dermal irritation, as well as hepatic and renal damage. (NCI04)
A benzodioxane alpha-adrenergic blocking agent with considerable stimulatory action. It has been used to diagnose PHEOCHROMOCYTOMA and as an antihypertensive agent.
A piperazine derivative with potential antineoplastic alkyating activity. Although the exact mechanism of action of pipobroman has yet to be fully elucidated, this agent appears to act by alkylating DNA, leading to disruption of DNA replication and eventually cell death.
A compound suggested to be both a nootropic and a neuroprotective agent.
An antimuscarinic agent that inhibits gastric secretion at lower doses than are required to affect gastrointestinal motility, salivary, central nervous system, cardiovascular, ocular, and urinary function. It promotes the healing of duodenal ulcers and due to its cytoprotective action is beneficial in the prevention of duodenal ulcer recurrence. It also potentiates the effect of other antiulcer agents such as CIMETIDINE and RANITIDINE. It is generally well tolerated by patients.
A dopamine D2 agonist. It is used in the treatment of parkinson disease, particularly for alleviation of tremor. It has also been used for circulatory disorders and in other applications as a D2 agonist.
A diphenylpropylamine and opioid receptor agonist, with analgesic activity. Upon administration, piritramide binds to and activates mu-opioid receptors in the central nervous system (CNS), thereby mimicking the effects of endogenous opioids and producing analgesic relief.
A quinolone antibiotic with activity against gram-negative bacteria. Piromidic acid is used in the treatment of urinary tract and intestinal infections.
A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.
A benign epithelial tumor derived from intrinsic cells of the adenohypophysis.
A rare, potentially life-threatening disorder caused by acute ischemic infarction or hemorrhage in the pituitary gland. It is most often associated with the presence of a pituitary gland adenoma. Signs and symptoms include headache, vomiting, visual disturbances, and endocrine dysfunction.
A non-neoplastic or neoplastic disorder that affects the pituitary gland. Representative examples of non-neoplastic disorders include pituitary gland hypoplasia and apoplexy. Representative examples of neoplastic disorders include pituitary gland adenoma and carcinoma.
Hormones released from the neurohypophysis (PITUITARY GLAND, POSTERIOR). They include a number of peptides which are formed in the NEURONS in the HYPOTHALAMUS, bound to NEUROPHYSINS, and stored in the nerve terminals in the posterior pituitary. Upon stimulation, these peptides are released into the hypophysial portal vessel blood.
A benign or malignant neoplasm affecting the pituitary gland. The vast majority are adenomas arising from the anterior lobe of the pituitary gland.
A substance or extract from the neurohypophysis (PITUITARY GLAND, POSTERIOR).
A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. (Dorland, 27th ed)
A mild exanthematous inflammation of unknown etiology. It is characterized by the presence of salmon-colored maculopapular lesions. The most striking feature is the arrangement of the lesions such that the long axis is parallel to the lines of cleavage. The eruptions are usually generalized, affecting chiefly the trunk, and the course is often self-limiting.
Pityriasis rubra pilaris is an uncommon skin disorder characterized by the appearance of keratotic follicular papules, well-demarcated salmon-colored erythematous plaques covered with fine powdery scales interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. Most cases are sporadic, although up to 6.5% of PRP-affected individuals report a positive family history. The rare familial cases show autosomal dominant inheritance with incomplete penetrance and variable expression: the disorder is usually present at birth or appears during the first years of life and is characterized by prominent follicular hyperkeratosis, diffuse palmoplantar keratoderma, and erythema, with only a modest response to treatment (summary by Fuchs-Telem et al., 2012).
Serotonin antagonist used against MIGRAINE DISORDERS and vascular headaches.
Morbidly adherent placenta in which the chorionic villi attach to the myometrium, rather than being restricted to the decidua basalis.
A non-neoplastic or neoplastic disorder that affects the placenta. Representative examples include chorioamnionitis, hemangioma, and choriocarcinoma.
A condition in which the placenta is located over or near the internal os of the cervix, increasing the risk of hemorrhage.
Failure of the PLACENTA to deliver an adequate supply of nutrients and OXYGEN to the FETUS.
A Gram-negative bacterial infection caused by Yersinia pestis. It is usually transmitted to humans from bites of infected rodent fleas. It is manifested as a bubonic, septicemic, or pneumonic plague. In bubonic plague, the lymph nodes adjacent to the site of the skin bite are infected and enlarged. In septicemic plague, the infection spreads directly through the bloodstream. In pneumonic plague, the infection spreads to the lungs either following bubonic plague, or by inhalation of infective droplets. If untreated, it may lead to death.
A suspension of killed Yersinia pestis used for immunizing people in enzootic plague areas.
Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.
A localized proliferation of plant tissue forming a swelling or outgrowth, commonly with a characteristic shape and unlike any organ of the normal plant. Plant tumors or galls usually form in response to the action of a pathogen or a pest. (Holliday, P., A Dictionary of Plant Pathology, 1989, p330)
Any liquid used to replace blood plasma, usually a saline solution, often with serum albumins, dextrans or other preparations. These substances do not enhance the oxygen- carrying capacity of blood, but merely replace the volume. They are also used to treat dehydration.
A discrete mass of neoplastic monoclonal plasma cells either in the bone marrow or in an extramedullary location.
Plasminogen (810 aa, ~91 kDa) is encoded by the human PLG gene. This protein is involved in fibrinolysis, platelet activation and tissue remodeling.
A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.
A family of serine proteases that catalyze the proteolytic conversion of plasminogen to plasmin.
Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system.
Disorder characterized by a decrease or lack of platelet dense bodies in which the releasable pool of adenine nucleotides and 5HT are normally stored.
A developmental deformity of the occipital bone and upper end of the cervical spine, in which the latter appears to have pushed the floor of the occipital bone upward. (Dorland, 27th ed)
A non-neoplastic or neoplastic disorder that affects the pleura. Representative examples include pleural infection, pleural mesothelioma, and pleural solitary fibrous tumor.
Increased amounts of fluid within the pleural cavity. Symptoms include shortness of breath, cough, and chest pain. It is usually caused by lung infections, congestive heart failure, pleural and lung tumors, connective tissue disorders, and trauma.
A benign or malignant neoplasm that involves the serous membrane that lines the lungs and thoracic cavity. Most pleural neoplasms are metastatic. Diffuse malignant mesothelioma is the most common primary malignant neoplasm of the pleura.
INFLAMMATION of PLEURA, the lining of the LUNG. When PARIETAL PLEURA is involved, there is pleuritic CHEST PAIN.
An acute, febrile, infectious disease generally occurring in epidemics. It is usually caused by coxsackieviruses B and sometimes by coxsackieviruses A; echoviruses; or other enteroviruses.
Inflammation of the lung parenchyma that is associated with PLEURISY, inflammation of the PLEURA.
A pleuropneumonia of cattle and goats caused by species of MYCOPLASMA.
A syndrome characterized by dysphagia, upper esophageal webs, iron deficiency anemia, and glossitis.
A naturally radioactive element of the actinide metals series. It has the atomic symbol Pu, and atomic number 94. Plutonium is used as a nuclear fuel, to produce radioisotopes for research, in radionuclide batteries for pacemakers, and as the agent of fission in nuclear weapons.
A condition characterized by the presence of multiple gas-filled cysts in the intestinal wall, the submucosa and/or subserosa of the INTESTINE. The majority of the cysts are found in the JEJUNUM and the ILEUM.
Presence of air or gas within the intracranial cavity (e.g., epidural space, subdural space, intracerebral, etc.) which may result from traumatic injuries, fistulous tract formation, erosions of the skull from NEOPLASMS or infection, NEUROSURGICAL PROCEDURES, and other conditions.
Infections with bacteria of the species STREPTOCOCCUS PNEUMONIAE.
A diffuse parenchymal lung disease caused by inhalation of dust and by tissue reaction to their presence. These inorganic, organic, particulate, or vaporized matters usually are inhaled by workers in their occupational environment, leading to the various forms (ASBESTOSIS; BYSSINOSIS; and others). Similar air pollution can also have deleterious effects on the general population.
An acute, acute and chronic, or chronic inflammation focally or diffusely affecting the lung parenchyma, due to infections (viruses, fungi, mycoplasma, or bacteria), treatment (e.g. radiation), or exposure (inhalation) to chemicals. Symptoms include cough, shortness of breath, fevers, chills, chest pain, headache, sweating, and weakness.
A type of lung inflammation resulting from the aspiration of food, liquid, or gastric contents into the upper RESPIRATORY TRACT.
A cattle disease of uncertain cause, probably an allergic reaction.
Pneumonia due to aspiration or inhalation of various oily or fatty substances.
Interstitial pneumonia caused by extensive infection of the lungs (LUNG) and BRONCHI, particularly the lower lobes of the lungs, by MYCOPLASMA PNEUMONIAE in humans. In SHEEP, it is caused by MYCOPLASMA OVIPNEUMONIAE. In CATTLE, it may be caused by MYCOPLASMA DISPAR.
Chronic respiratory disease caused by the VISNA-MAEDI VIRUS. It was formerly believed to be identical with jaagsiekte (PULMONARY ADENOMATOSIS, OVINE) but is now recognized as a separate entity.
Pneumonia caused by infection with bacteria of the family RICKETTSIACEAE.
Pneumonia caused by infections with bacteria of the genus STAPHYLOCOCCUS, usually with STAPHYLOCOCCUS AUREUS.
Inflammation of the lung parenchyma that is caused by a viral infection.
Presence of air or gas in the space between the heart and the PERICARDIUM. The degree of respiratory distress depends on the amount of trapped air and circulation blocked in the systemic and pulmonary veins.
A condition with trapped gas or air in the PERITONEAL CAVITY, usually secondary to perforation of the internal organs such as the LUNG and the GASTROINTESTINAL TRACT, or to recent surgery. Pneumoperitoneum may be purposely introduced to aid radiological examination.
Abnormal presence of air in the pleural cavity.
A resin extracted from the root of the plant Podophyllum sp. Berberidaceae (mandrake), which contains numerous compounds, among which podophyllotoxin is the principal active component. Podophyllin arrests mitosis in metaphase. Podophyllotoxin offers advantages over podophyllin in terms of purity, stability and lack of systemic toxicity. (NCI04)
A lignan (LIGNANS) found in PODOPHYLLIN resin from the roots of PODOPHYLLUM plants. It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives.
Rothmund-Thomson syndrome (RTS) is characterized by a rash that progresses to poikiloderma; sparse hair, eyelashes, and/or eyebrows; small size; skeletal and dental abnormalities; cataracts; and an increased risk for cancer, especially osteosarcoma. The skin is typically normal at birth; the rash of RTS develops between ages three and six months as erythema, swelling, and blistering on the face, subsequently spreading to the buttocks and extremities. The rash evolves over months to years into the chronic pattern of reticulated hypo- and hyperpigmentation, punctate atrophy, and telangiectasias, collectively known as poikiloderma. Hyperkeratotic lesions occur in approximately one third of individuals. Skeletal abnormalities include radial ray defects, ulnar defects, absent or hypoplastic patella, and osteopenia.
An allergic contact dermatitis caused by exposure to plants of the genus Toxicodendron (formerly Rhus). These include poison ivy, poison oak, and poison sumac, all plants that contain the substance urushiol, a potent skin sensitizing agent. (From Dorland, 27th ed)
Poland syndrome consists of unilateral absence or hypoplasia of the pectoralis muscle, most frequently involving the sternocostal portion of the pectoralis major muscle, and a variable degree of ipsilateral hand and digit anomalies, including symbrachydactyly. Sometimes called Poland sequence, it was first described by Poland (1841). Poland syndrome is most commonly a sporadic condition (David, 1982; Opitz, 1982), but familial cases have been reported.
An acute infectious disease of humans, particularly children, caused by any of three serotypes of human poliovirus (POLIOVIRUS). Usually the infection is limited to the gastrointestinal tract and nasopharynx, and is often asymptomatic. The central nervous system, primarily the spinal cord, may be affected, leading to rapidly progressive paralysis, coarse FASCICULATION and hyporeflexia. Motor neurons are primarily affected. Encephalitis may also occur. The virus replicates in the nervous system, and may cause significant neuronal loss, most notably in the spinal cord. A rare related condition, nonpoliovirus poliomyelitis, may result from infections with nonpoliovirus enteroviruses. (From Adams et al., Principles of Neurology, 6th ed, pp764-5)
A form of paralytic poliomyelitis affecting neurons of the MEDULLA OBLONGATA of the brain stem. Clinical features include impaired respiration, HYPERTENSION, alterations of vasomotor control, and dysphagia. Weakness and atrophy of the limbs and trunk due to spinal cord involvement is usually associated. (From Adams et al., Principles of Neurology, 6th ed, p765)
Vaccines used to prevent POLIOMYELITIS. They include inactivated (POLIOVIRUS VACCINE, INACTIVATED) and oral vaccines (POLIOVIRUS VACCINE, ORAL).
A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed)
A copolymer of polyethylene and polypropylene ether glycol. It is a non-ionic polyol surface-active agent used medically as a fecal softener and in cattle for prevention of bloat.
A synthetic polyadenylic-polyuridylic acid double-stranded RNA. Poly AU may stimulate the release of cytotoxic cytokines and, by inducing the production of interferon, may increase the number and tumoricidal activities of various immunohematopoietic cells. (NCI04)
A synthetic polyinosinic-polycytidylic acid double-stranded RNA. Poly IC may stimulate the release of cytotoxic cytokines and, by inducing interferon-gamma production, may increase the number and tumoricidal activities of various immunohematopoietic cells. (NCI04)
A compound originally developed as an anticoagulant, but possessing anticomplement action and lowering the bactericidal action of blood. It is used in vitro to inhibit blood coagulation and as a diagnostic reagent to encourage the growth of pathogens in the blood. It is also used to stabilize colloidal solutions such as milk and gelatin. (From Merck Index, 11th ed)
An acquired disease of unknown etiology, chronic course, and tendency to recur. It is characterized by inflammation and degeneration of cartilage and can result in deformities such as floppy ear and saddle nose. Loss of cartilage in the respiratory tract can lead to respiratory obstruction.
Polycystic ovary syndrome is a condition that affects women in their child-bearing years and alters the levels of multiple hormones, resulting in problems affecting many body systems.Most women with polycystic ovary syndrome produce excess male sex hormones (androgens), a condition called hyperandrogenism. Having too much of these hormones typically leads to excessive body hair growth (hirsutism), acne, and male pattern baldness.Hyperandrogenism and abnormal levels of other sex hormones prevent normal release of egg cells from the ovaries (ovulation) and regular menstrual periods, leading to difficulty conceiving a child (subfertility) or a complete inability to conceive (infertility). For those who achieve pregnancy, there is an increased risk of complications and pregnancy loss. Due to irregular and infrequent menstruation and hormone abnormalities, affected women have an increased risk of cancer of the uterine lining (endometrial cancer).In polycystic ovary syndrome, multiple cysts in each ovary can be seen with medical imaging. These cysts are small, immature ovarian follicles. Normally, ovarian follicles contain egg cells, which are released during ovulation. In polycystic ovary syndrome, abnormal hormone levels prevent follicles from growing and maturing to release egg cells. Instead, these immature follicles accumulate in the ovaries. Affected women can have 12 or more of these follicles. The number of these follicles usually decreases with age.About half of all women with polycystic ovary syndrome are overweight or obese and are at increased risk of a fatty liver. Additionally, many women with polycystic ovary syndrome have elevated levels of insulin, which is a hormone that helps control blood sugar levels. By age 40, about 10 percent of overweight women with polycystic ovary syndrome develop abnormally high blood sugar levels (type 2 diabetes), and up to 35 percent develop prediabetes (higher-than-normal blood sugar levels that do not reach the cutoff for diabetes). Obesity and increased insulin levels (hyperinsulinemia) further increase the production of androgens in polycystic ovary syndrome.Women with polycystic ovary syndrome are also at increased risk for developing metabolic syndrome, which is a group of conditions that include high blood pressure (hypertension), increased belly fat, high levels of unhealthy fats and low levels of healthy fats in the blood, and high blood sugar levels. About 20 percent of affected adults experience pauses in breathing during sleep (sleep apnea). Women with polycystic ovary syndrome are more likely to have mood disorders such as depression compared to the general population.
Abnormally high mass or concentration of red blood cells in the blood, either due to an increase in erythropoiesis or a decrease in plasma volume.
Polycythemia vera, the most common form of primary polycythemia, is caused by somatic mutation in a single hematopoietic stem cell leading to clonal hematopoiesis. PV is a myeloproliferative disorder characterized predominantly by erythroid hyperplasia, but also by myeloid leukocytosis, thrombocytosis, and splenomegaly. Familial cases of PV are very rare and usually manifest in elderly patients (Cario, 2005). PV is distinct from the familial erythrocytoses (see, e.g., ECYT1, 133100), which are caused by inherited mutations resulting in hypersensitivity of erythroid progenitors to hormonal influences or increased levels of circulating hormones, namely erythropoietin (EPO; 133170) (Prchal, 2005).
Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS.
A 3.5 per cent colloidal solution containing urea-cross-linked polymerized peptides. It has a molecular weight of approximately 35,000 and is prepared from gelatin and electrolytes. The polymeric solution is used as a plasma expander.
Frequent menses; menstrual cycles lasting less than 21 days.
A syndrome characterized by pain, stiffness, and tenderness of the proximal muscle groups including the shoulder, pelvic girdle and the neck. There is no muscle atrophy and muscle biopsies do not reveal pathologic changes. Additional signs and symptoms include low grade fever, fatigue and depression.
A polymeric mixture of polyesters of phosphoric acid and phloretin. It blocks some cellular responses to prostaglandins.
A numerical chromosomal abnormality characterized by the presence of more than two sets of chromosomes.
Familial adenomatous polyposis (FAP) is an inherited disorder characterized by cancer of the large intestine (colon) and rectum. People with the classic type of familial adenomatous polyposis may begin to develop multiple noncancerous (benign) growths (polyps) in the colon as early as their teenage years. Unless the colon is removed, these polyps will become malignant (cancerous). The average age at which an individual develops colon cancer in classic familial adenomatous polyposis is 39 years. Some people have a variant of the disorder, called attenuated familial adenomatous polyposis, in which polyp growth is delayed. The average age of colorectal cancer onset for attenuated familial adenomatous polyposis is 55 years.In people with classic familial adenomatous polyposis, the number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon. Also of particular significance are noncancerous growths called desmoid tumors. These fibrous tumors usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. Desmoid tumors tend to recur after they are surgically removed. In both classic familial adenomatous polyposis and its attenuated variant, benign and malignant tumors are sometimes found in other places in the body, including the duodenum (a section of the small intestine), stomach, bones, skin, and other tissues. People who have colon polyps as well as growths outside the colon are sometimes described as having Gardner syndrome.A milder type of familial adenomatous polyposis, called autosomal recessive familial adenomatous polyposis, has also been identified. People with the autosomal recessive type of this disorder have fewer polyps than those with the classic type. Fewer than 100 polyps typically develop, rather than hundreds or thousands. The autosomal recessive type of this disorder is caused by mutations in a different gene than the classic and attenuated types of familial adenomatous polyposis.
A usually exophytic mass attached to the underlying tissue by a broad base or a thin stalk. Polyps can be neoplastic or non-neoplastic. Neoplastic polyps usually represent proliferations of the epithelium, and are commonly seen in the gastrointestinal tract. Polyps of the gastrointestinal tract are often called adenomas, are associated with dysplasia, and may eventually transform into carcinomas. Non-neoplastic polyps may be inflammatory, degenerative, or the result of malformations.
A radiculopathy that is present in more than one nerve.
Diseases characterized by injury or dysfunction involving multiple peripheral nerves and nerve roots. The process may primarily affect myelin or nerve axons. Two of the more common demyelinating forms are acute inflammatory polyradiculopathy (GUILLAIN-BARRE SYNDROME) and POLYRADICULONEUROPATHY, CHRONIC INFLAMMATORY DEMYELINATING. Polyradiculoneuritis refers to inflammation of multiple peripheral nerves and spinal nerve roots.
A large carbohydrate molecule. It contains many small sugar molecules that are joined chemically.
A long acting benzothiadiazine sulfonamide derivative belonging to the class of the thiazide diuretics. Polythiazide is excreted mainly in its unchanged form.
Inhibits the cytotoxic action of quartz and is reported to have delayed the development of experimental silicosis in rats.
Self-limited vesicular eruption of palms and soles
Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. Heme is a vital molecule for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is a component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. Some types of porphyria, called cutaneous porphyrias, primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria, hepatoerythropoietic porphyria, and porphyria cutanea tarda.Other types of porphyria, called acute porphyrias, primarily affect the nervous system. These disorders are described as ""acute"" because their signs and symptoms appear quickly and usually last a short time. Episodes of acute porphyria can cause abdominal pain, vomiting, constipation, and diarrhea. During an episode, a person may also experience muscle weakness, seizures, fever, and mental changes such as anxiety and hallucinations. These signs and symptoms can be life-threatening, especially if the muscles that control breathing become paralyzed. Acute porphyrias include acute intermittent porphyria and ALAD deficiency porphyria. Two other forms of porphyria, hereditary coproporphyria and variegate porphyria, can have both acute and cutaneous symptoms.The porphyrias can also be split into erythropoietic and hepatic types, depending on where damaging compounds called porphyrins and porphyrin precursors first build up in the body. In erythropoietic porphyrias, these compounds originate in the bone marrow. Erythropoietic porphyrias include erythropoietic protoporphyria and congenital erythropoietic porphyria. Health problems associated with erythropoietic porphyrias include a low number of red blood cells (anemia) and enlargement of the spleen (splenomegaly). The other types of porphyrias are considered hepatic porphyrias. In these disorders, porphyrins and porphyrin precursors originate primarily in the liver, leading to abnormal liver function and an increased risk of developing liver cancer.Environmental factors can strongly influence the occurrence and severity of signs and symptoms of porphyria. Alcohol, smoking, certain drugs, hormones, other illnesses, stress, and dieting or periods without food (fasting) can all trigger the signs and symptoms of some forms of the disorder. Additionally, exposure to sunlight worsens the skin damage in people with cutaneous porphyrias.
A cutaneous form of leishmaniasis which sometimes occurs after visceral leishmaniasis treatment. It is characterized by hypo-pigmented macules, papules, plaques, nodules, or facial erythema; and is considered to be a durable infection reservoir for visceral leishmaniasis.
Sequelae of gastrectomy from the second week after operation on. Include recurrent or anastomotic ulcer, postprandial syndromes (DUMPING SYNDROME and late postprandial hypoglycemia), disordered bowel action, and nutritional deficiencies.
Pain in nerves, frequently involving facial SKIN, resulting from the activation the latent varicella-zoster virus (HERPESVIRUS 3, HUMAN). The two forms of the condition preceding the pain are HERPES ZOSTER OTICUS; and HERPES ZOSTER OPHTHALMICUS. Following the healing of the rashes and blisters, the pain sometimes persists.
Uterine bleeding occurring after menopause.
Physiological changes that occur in bodies after death.
Excessive mucous secretion in the back of the nasal cavity or throat, causing sore throat and/or coughing. It is usually due to allergic rhinitis or a cold.
Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.
Bleeding occurring after completion of a surgical procedure, which may occur immediately or may be delayed, and which may or may not be wound related.
A state of shock following a surgical operation.
Excess blood loss from uterine bleeding associated with OBSTETRIC LABOR or CHILDBIRTH. It is defined as blood loss greater than 500 ml or of the amount that adversely affects the maternal physiology, such as BLOOD PRESSURE and HEMATOCRIT. Postpartum hemorrhage is divided into two categories, immediate (within first 24 hours after birth) or delayed (after 24 hours postpartum).
A nonspecific hypersensitivity reaction caused by TRAUMA to the PERICARDIUM, often following PERICARDIOTOMY. It is characterized by PERICARDIAL EFFUSION; high titers of anti-heart antibodies; low-grade FEVER; LETHARGY; loss of APPETITE; or ABDOMINAL PAIN.
A condition characterized by a chronically swollen limb, often a leg with stasis dermatitis and ulcerations. This syndrome can appear soon after phlebitis or years later. Postphlebitic syndrome is the result of damaged or incompetent venous valves in the limbs. Distended, tortuous VARICOSE VEINS are usually present. Leg pain may occur after long period of standing.
Secondary headache attributed to TRAUMA of the HEAD and/or the NECK.
An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
A metal halide composed of potassium and chloride. Potassium maintains intracellular tonicity, is required for nerve conduction, cardiac, skeletal and smooth muscle contraction, production of energy, the synthesis of nucleic acids, maintenance of blood pressure and normal renal function. This agent has potential antihypertensive effects and when taken as a nutritional supplement may prevent hypokalemia.
A condition due to decreased dietary intake of potassium, as in starvation or failure to administer in intravenous solutions, or to gastrointestinal loss in diarrhea, chronic laxative abuse, vomiting, gastric suction, or bowel diversion. Severe potassium deficiency may produce muscular weakness and lead to paralysis and respiratory failure. Muscular malfunction may result in hypoventilation, paralytic ileus, hypotension, muscle twitches, tetany, and rhabomyolysis. Nephropathy from potassium deficit impairs the concentrating mechanism, producing POLYURIA and decreased maximal urinary concentrating ability with secondary POLYDIPSIA. (Merck Manual, 16th ed)
An orange to red colored, crystalline, inorganic compound that emits toxic chromium fumes upon heating. Potassium dichromate is highly corrosive and is a strong oxidizing agent. This substance is used in wood preservatives, in the manufacture of pigments and in photomechanical processes, but is mainly replaced by sodium dichromate. Potassium dichromate primarily affects the respiratory tract causing ulcerations, shortness of breath, bronchitis, pneumonia and asthma but can also affect the gastrointestinal tract, liver, kidneys and immune system. This substance is a known human carcinogen and is associated with an increased risk of developing lung cancer and cancer of the sinonasal cavity. (NCI05)
A metal halide composed of potassium and iodide with thyroid protecting and expectorant properties. Potassium iodide can block absorption of radioactive iodine by the thyroid gland through flooding the thyroid with non-radioactive iodine and preventing intake of radioactive molecules, thereby protecting the thyroid from cancer causing radiation. In addition, this agent acts as an expectorant by increasing secretion of respiratory fluids resulting in decreased mucus viscosity.
An intra-extracellular electrolyte exchange agent with a variety of effects.
Permanganic acid (HMnO4), potassium salt. A highly oxidative, water-soluble compound with purple crystals, and a sweet taste. (From McGraw-Hill Dictionary of Scientific and Technical Information, 4th ed)
Diseases of birds which are raised as a source of meat or eggs for human consumption and are usually found in barnyards, hatcheries, etc. The concept is differentiated from BIRD DISEASES which is for diseases of birds not considered poultry and usually found in zoos, parks, and the wild.
A polyvinyl polymer of variable molecular weight; used as suspending and dispersing agent and vehicle for pharmaceuticals; also used as blood volume expander.
An iodinated polyvinyl polymer used as topical antiseptic in surgery and for skin and mucous membrane infections, also as aerosol. The iodine may be radiolabeled for research purposes.
Virus diseases caused by the POXVIRIDAE.
A beta-1 adrenergic antagonist that has been used in the emergency treatment of CARDIAC ARRYTHMIAS.
Prader-Willi syndrome (PWS) is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of morbid obesity (unless eating is externally controlled). Motor milestones and language development are delayed. All individuals have some degree of cognitive impairment. A distinctive behavioral phenotype (with temper tantrums, stubbornness, manipulative behavior, and obsessive-compulsive characteristics) is common. Hypogonadism is present in both males and females and manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature is common (if not treated with growth hormone); characteristic facial features, strabismus, and scoliosis are often present.
A derivative of the rauwolfia alkaloid AJMALINE. It is an anti-arrhythmia agent, but may cause liver damage.
A benzodiazepine that is used in the treatment of ANXIETY DISORDERS.
A pyrazinoisoquinoline derivative with anthelminthic property. Praziquantel increases the permeability of the tegument of susceptible worms, resulting in an influx and increase in intra-tegumental calcium leading to rapid contractions and paralysis of the worm's musculature through a subsequent increase in levels of calcium in the sarcoplasmic reticulum. In addition, vacuolization of the tegumental syncytium and blebbing results in tegument disintegration, leads to antigen exposure and elicit host defense responses to the worm. The result is the formation of granulomas and phagocytosis.
A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.
Preeclampsia, which along with chronic hypertension and gestational hypertension comprise the hypertensive disorders of pregnancy, is characterized by new hypertension (blood pressure 140/90 or greater) presenting after 20 weeks' gestation with clinically relevant proteinuria. Preeclampsia is 1 of the top 4 causes of maternal mortality and morbidity worldwide (summary by Payne et al., 2011). Preeclampsia is otherwise known as gestational proteinuric hypertension (Davey and MacGillivray, 1988). A high proportion of patients with preeclampsia have glomerular endotheliosis, the unique histopathologic feature of the condition (Fisher et al., 1981). A distinct form of severe preeclampsia is characterized by hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome) (Brown et al., 2000). Genetic Heterogeneity of Preeclampsia/Eclampsia Susceptibility loci for preeclampsia/eclampsia include PEE1 on chromosome 2p13, PEE2 (609402) on chromosome 2p25, and PEE3 (609403) on chromosome 9p13. PEE4 (609404) is caused by mutation in the STOX1 gene (609397) on chromosome 10q22. PEE5 (614595) is caused by mutation in the CORIN gene (605236) on chromosome 4p12. An association with PEE has been found with the EPHX1 gene (132810) on chromosome 1q.
An electrocardiographic finding characterized by a premature activation of the whole or some part of the ventricle. The PR interval is usually shortened and delta waves are frequently present. (CDISC)
A form of ventricular pre-excitation characterized by a normal PR interval and a long QRS interval with an initial slow deflection (delta wave). In this syndrome, the atrial impulse travel to the ventricle via the MAHAIM FIBERS which connect ATRIOVENTRICULAR NODE directly to the right ventricle wall (NODOVENTRICULAR ACCESSORY PATHWAY) or to the RIGHT BUNDLE BRANCH OF HIS (nodofascicular accessory pathway).
A pathological process with signs indicating it may become cancerous. Representative examples include leukoplakia, dysplastic nevus, actinic keratosis, xeroderma pigmentosum, and intraepithelial neoplasia.
The prednisolone ester of chlorambucil and nitrogen mustard alkylating agent with antineoplastic activity. Prednimustine itself is not cytotoxic, however, it becomes cytotoxic upon hydrolysis by serum esterases to chlorambucil. Therefore, the increased potency of prednimustine is linked to the prolonged availability of free chlorambucil.
A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.
A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.
The co-occurrence of pregnancy and a disease. The disease may precede or follow conception and it may or may not have a deleterious effect on the pregnant woman or fetus.
The co-occurrence of pregnancy and a cardiovascular disease. The disease may precede or follow FERTILIZATION and it may or may not have a deleterious effect on the pregnant woman or FETUS.
The co-occurrence of pregnancy and a blood disease (HEMATOLOGIC DISEASES) which involves BLOOD CELLS or COAGULATION FACTORS. The hematologic disease may precede or follow FERTILIZATION and it may or may not have a deleterious effect on the pregnant woman or FETUS.
The co-occurrence of pregnancy and an INFECTION. The infection may precede or follow FERTILIZATION.
The co-occurrence of pregnancy and NEOPLASMS. The neoplastic disease may precede or follow FERTILIZATION.
A pregnancy in an adolescent between the ages of thirteen and nineteen.
The state of PREGNANCY in women with DIABETES MELLITUS. This does not include either symptomatic diabetes or GLUCOSE INTOLERANCE induced by pregnancy (DIABETES, GESTATIONAL) which resolves at the end of pregnancy.
Findings observed at the end of a pregnancy.
A type of ectopic pregnancy in which the EMBRYO, MAMMALIAN implants in the ABDOMINAL CAVITY instead of in the ENDOMETRIUM of the UTERUS.
A potentially life-threatening condition in which EMBRYO IMPLANTATION occurs outside the cavity of the UTERUS. Most ectopic pregnancies (>96%) occur in the FALLOPIAN TUBES, known as TUBAL PREGNANCY. They can be in other locations, such as UTERINE CERVIX; OVARY; and abdominal cavity (PREGNANCY, ABDOMINAL).
A gestation with more than one fertilized egg implanted as a viable fetus in the uterus.
A type of pregnancy in which EMBRYO IMPLANTATION occurs in an OVARY instead of in the uterine cavity.
A gestation that lasts greater than or equal to 42 weeks and 0 days.
An abnormal pregnancy in which the conception is implanted in the fallopian tube.
Pregnancy, usually accidental, that is not desired by the parent or parents.
A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.
A catatoxic steroid and microsomal enzyme inducer having significant effects on the induction of cytochrome P450. It has also demonstrated the potential for protective capability against acetaminophen-induced liver damage.
Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria.
A type of cardiac arrhythmia with premature atrial contractions or beats caused by signals originating from ectopic atrial sites.
A disorder characterized by persistent or recurrent ejaculation before or after penetration and before the person wishes it.
A combination of distressing physical, psychologic, or behavioral changes that occur during the luteal phase of the menstrual cycle. Symptoms of PMS are diverse (such as pain, water-retention, anxiety, cravings, and depression) and they diminish markedly 2 or 3 days after the initiation of menses.
A partial adrenergic agonist with functional beta 1-receptor specificity and inotropic effect. It is effective in the treatment of acute CARDIAC FAILURE, postmyocardial infarction low-output syndrome, SHOCK, and reducing ORTHOSTATIC HYPOTENSION in the SHY-RAGER SYNDROME.
A pyrazole that has analgesic, anti-inflammatory, and antipyretic properties. It has been used in mild to moderate pain, fever, and inflammation associated with musculoskeletal and joint disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p15)
A drug formerly used in the treatment of angina pectoris but superseded by less hazardous drugs. Prenylamine depletes myocardial catecholamine stores and has some calcium channel blocking activity. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1406)
Bilateral hearing loss caused by progressive degeneration of cochlear structures and central auditory pathways, typically associated with the aging process.
The normal decreasing elasticity of the crystalline lens that leads to loss of accommodation.
A diffuse, non-pitting edema and thickening of the skin usually on the anterior aspect of the lower legs spreading to the dorsum of the feet.
A painful and harmful medical condition in which the erect penis doesn't return to its flaccid state, despite the absence of both physical and psychological stimulation, within four hours.
A local anesthetic that is similar pharmacologically to LIDOCAINE. Currently, it is used most often for infiltration anesthesia in dentistry.
A synthetic, 8-aminoquinoline derivative with antimalarial properties. Although its mechanism of action is unclear, primaquine bind to and alter the properties of protozoal DNA. This agent eliminates tissue (exo-erythrocytic) malarial infection, preventing the development of the erythrocytic forms of the parasite which are responsible for relapses in Plasmodium vivax and ovale malaria. Primaquine is active against late hepatic stages (hypnozoites, schizonts). (NCI04)
The phosphate salt form of primaquine, a synthetic, 8-aminoquinoline derivative with antimalarial properties. Although its mechanism of action is unclear, primaquine bind to and alter the properties of protozoal DNA. This agent eliminates tissue (exo-erythrocytic) malarial infection, preventing the development of the erythrocytic forms of the parasite which are responsible for relapses in Plasmodium vivax and ovale malaria. Primaquine is active against late hepatic stages (hypnozoites, schizonts).
A disorder of central nervous system etiology characterized by excessive sleepiness during the daytime.
A sleep disorder characterized by difficulty initiating or maintaining sleep; this difficulty does not occur in the context of another sleep disorder and is not etiologically linked to a mental disorder, substance use, or a general medical condition.
A disease of the heart muscle or myocardium proper whose cause is unknown.
A barbiturate derivative that acts as a GABA modulator and anti-epileptic agent. It is partly metabolized to PHENOBARBITAL in the body and owes some of its actions to this metabolite.
Pregnant with, or having borne, only one child or offspring.
An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.
A benzoic acid derivative with antihyperuricemic property. Probenecid competitively inhibits the active reabsorption of urate at the proximal tubule in the kidney thereby increasing urinary excretion of uric acid and lowering serum urate concentrations. This prevents urate deposition and promotes resolution of existing urate deposits. In addition, probenecid modulates the transport of organic acids and acidic drugs at the proximal and distal renal tubule, thereby increasing the drug serum concentration.
A difficulty, disorder, or condition needing resolution.
A bis-phenol antioxidant with antilipidemic activity. Probucol inhibits oxidation of low density lipoprotein and lowers the level of cholesterol in the bloodstream by increasing the rate of LDL catabolism.
A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.
A benzoic acid derivative with local anesthetic and antiarrhythmic properties. Procaine binds to and inhibits voltage-gated sodium channels, thereby inhibiting the ionic flux required for the initiation and conduction of impulses. In addition, this agent increases electrical excitation threshold, reduces rate of rise of action potential and slows nerve impulse propagation thereby causing loss of sensation.
A methylhydrazine derivative with antineoplastic and mutagenic activities. Although the exact mode of cytotoxicity has not been elucidated, procarbazine, after metabolic activation, appears to inhibit the trans-methylation of methionine into transfer RNA (t-RNA), thereby preventing protein synthesis and consequently DNA and RNA synthesis. This agent may also undergo auto-oxidation, resulting in the formation of cytotoxic free radicals which damage DNA through an alkylation reaction.
A synthetic phenoxy-isobutyric acid derivate and prodrug with antihyperlipidemic activity. Fenofibrate is hydrolyzed in vivo to its active metabolite fenofibric acid that binds to and activates peroxisome proliferator activated receptor alpha (PPARalpha), resulting in the activation of lipoprotein lipase and reduction of the production of apoprotein C-III, an inhibitor of lipoprotein lipase activity. Increased lipolysis and a fall in plasma triglycerides, in turn, leads to the modification of the small, dense low density lipoporotein (LDL) particles into larger particles that are catabolized more rapidly due to a greater affinity for cholesterol receptors. In addition, activation of PPARalpha also increases the synthesis of apoproteins A-I, A-II, and high density lipoprotein (HDL)-cholesterol. Overall, fenofibrate reduces total cholesterol, LDL cholesterol, apolipoprotein B, total triglycerides and triglyceride rich lipoprotein (VLDL) while increasing HDL cholesterol.
A phenothiazine antipsychotic used principally in the treatment of NAUSEA; VOMITING; and VERTIGO. It is more likely than CHLORPROMAZINE to cause EXTRAPYRAMIDAL DISORDERS. (From Martindale, The Extra Pharmacopoeia, 30th ed, p612)
The edisylate salt form of prochlorperazine, a derivative of phenothiazine with antipsychotic and antiemetic properties. Prochlorperazine edisylate blocks postsynaptic dopamine receptors in cortical and limbic areas of the brain, thereby preventing the excess of dopamine in the brain. This leads to a reduction in psychotic symptoms, including hallucinations and delusions. Prochlorperazine edisylate appears to exert its antiemetic activity by blocking the dopamine and histamine receptors in the chemical trigger zone (CTZ) in the brain, thereby relieving nausea and vomiting.
The maleate salt form of prochlorperazine, a synthetic, piperazine phenothiazine derivative with antiemetic, antipsychotic, antihistaminic, and anticholinergic activities. Prochlorperazine binds to and blocks the postsynaptic dopamine D2-receptor in the chemoreceptor trigger zone (CTZ) of the brain and may prevent chemotherapy-induced emesis. Prochlorperazine maleate also blocks anticholinergic and alpha-adrenergic receptors. Its antagonistic actions on the alpha-1 adrenergic receptors results in sedation, muscle relaxation, and hypotension.
An inflammatory process affecting the anus. It is usually caused by sexually transmitted infectious agents and/or inflammatory bowel disease.
Inflammation of the RECTUM and the distal portion of the COLON.
Inflammation of the sigmoid colon and rectum.
A muscarinic antagonist that crosses the blood-brain barrier and is used in the treatment of drug-induced extrapyramidal disorders and in parkinsonism.
4-Methoxy-5-((5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl)- 2,2'-bi-1H-pyrrole. A toxic, bright red tripyrrole pigment from Serratia marcescens and others. It has antibacterial, anticoccidial, antimalarial, and antifungal activities, but is used mainly as a biochemical tool.
A polysaccharide extracted from Serratia marcescens and other bacteria. It activates enzymatic activity of macrophages and stimulates phagocytic processes.
Topical antiseptic used mainly in wound dressings.
The hemisulfate salt form of proflavine, an acridine-derived fluorescent contrast and disinfectant agent that can potentially be used for cellular imaging and antiseptic purposes. Upon topical application of proflavine hemisulfate, proflavine diffuses into cells and intercalates into DNA, thereby accumulating in and staining the nucleus. During fluorescence imaging, the cell nuclei can be visualized. This allows nuclear morphometry and the identification of cancer cells. In addition, proflavine exerts its antibacterial effect by binding to bacterial DNA, thereby disrupting DNA synthesis and halting bacterial cell growth.
Hutchinson-Gilford progeria syndrome (HGPS) is characterized by clinical features that typically develop in childhood and resemble some features of accelerated aging. Children with HGPS usually appear normal at birth. Profound failure to thrive occurs during the first year. Characteristic facial features include head that is disproportionately large for the face, narrow nasal ridge, narrow nasal tip, thin vermilion of the upper and lower lips, small mouth, and retro- and micrognathia. Common features include loss of subcutaneous fat, delayed eruption and loss of primary teeth, abnormal skin with small outpouchings over the abdomen and upper thighs, alopecia, nail dystrophy, coxa valga, and progressive joint contractures. Later findings include low-frequency conductive hearing loss, dental crowding, and partial lack of secondary tooth eruption. Motor and mental development is normal. Death occurs as a result of complications of severe atherosclerosis, either cardiac disease (myocardial infarction or heart failure) or cerebrovascular disease (stroke), generally between ages six and 20 years. Average life span is approximately 14.5 years.
Compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE. Primary actions of progestins, including natural and synthetic steroids, are on the UTERUS and the MAMMARY GLAND in preparation for and in maintenance of PREGNANCY.
A synthetic form of the endogenous hormone progesterone. Progesterone binds to the progesterone receptor, resulting in dissociation of heat shock proteins, receptor phosphorylation, and transcription activation through direct or indirect interaction with transcription factors. This agent exerts inhibitory effects on estrogens by decreasing the number of estrogen receptors and increasing its metabolism to inactive metabolites. Progesterone induces secretory changes in the endometrium, decreases uterine contractility during pregnancy, and maintains pregnancy. (NCI04)
A condition marked by abnormal protrusion of the mandible. (Dorland, 27th ed)
A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate.
A hypothalamic hormone that is synthesized as a precursor protein which is cleaved into two peptides. In addition to stimulating PROLACTIN release the peptides bind to specific G-PROTEIN-COUPLED RECEPTORS found at locations within the BRAIN.
AIP-related isolated familial pituitary adenoma (AIP-related FIPA) is defined as the presence of an AIP germline pathogenic variant in an individual with a pituitary adenoma (regardless of family history). The most commonly occurring pituitary adenomas in this disorder are growth hormone-secreting adenomas (somatotropinoma), followed by prolactin-secreting adenomas (prolactinoma), growth hormone and prolactin co-secreting adenomas (somatomammotropinoma), and non-functioning pituitary adenomas (NFPA). Rarely TSH- or ACTH-secreting adenomas (thyrotropinoma and corticotropinoma) are observed. Clinical findings result from excess hormone secretion, lack of hormone secretion, and/or mass effects (e.g., headaches, visual field loss). Within the same family, pituitary adenomas can be of the same or different type. Age of onset in AIP-related FIPA is around 20-24 years (age range: 6-66 years).
A condition in which an organ or body tissue drops or bulges out of place.
A phenothiazine with actions similar to CHLORPROMAZINE but with less antipsychotic activity. It is primarily used in short-term treatment of disturbed behavior and as an antiemetic.
A narcotic analgesic similar to MEPERIDINE; it exists in four stereoisomers, two of which, the beta (isopromedol) and the gamma (trimeperidine) are active.
A synthetic progestin which is useful for the study of progestin distribution and progestin tissue receptors, as it is not bound by transcortin and binds to progesterone receptors with a higher association constant than progesterone.
A phenothiazine derivative with antiemetic and antihistaminic properties. Promethazine antagonizes the central and peripheral effects of histamine mediated by histamine H1 receptors. The effects include bronchoconstriction, vasodilation and spasmodic contractions of gastrointestinal smooth muscle. In addition, this agent binds to muscarinic receptors, resulting in anticholinergic and antiemetic activities.
An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.
An intravenous anesthetic that has been used for rapid induction of anesthesia and for maintenance of anesthesia of short duration. (From Martindale, The Extra Pharmacopoeia, 30th ed, p918)
AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.
A muscarinic antagonist used as an antispasmodic, in rhinitis, in urinary incontinence, and in the treatment of ulcers. At high doses it has nicotinic effects resulting in neuromuscular blocking.
The bromide salt form of propantheline, a quaternary ammonium compound structurally related to belladonna alkaloids. Propantheline bromide competitively antagonizes acetylcholine activity mediated by muscarinic receptors at neuroeffector sites on smooth muscle and exocrine gland cells. An aspartic acid residue present in the N-terminal portion of the third trans-membrane helix of the muscarinic receptor is believed to form an ionic bond with the tertiary or quaternary nitrogen of the antagonist. Antagonism leads to a reduction of exocrine glands secretions and to relax bronchial muscle and reduce tone and motility of intestinal smooth muscle.
A phenothiazine derivative and atypical antipsychotic agent with sedative, antiemetic and antipsychotic activities. Propiomazine binds to a variety of receptors, including alpha1, dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors. Propiomazine exerts its antiemetic and sedative effects through antagonism at histamine H1 receptors; Its antipsychotic effect is attributed to antagonistic activities at dopamine and 5-HT2 receptors.
A hypnotic alkylphenol derivative. Formulated for intravenous induction of sedation and hypnosis during anesthesia, propofol facilitates inhibitory neurotransmission mediated by gamma-aminobutyric acid (GABA). This agent is associated with minimal respiratory depression and has a short half-life with a duration of action of 2 to 10 minutes.
A resinous substance obtained from beehives that is used traditionally as an antimicrobial. It is a heterogeneous mixture of many substances.
A local anesthetic of the ester type that has a rapid onset of action and a longer duration of action than procaine hydrochloride. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1017)
A narcotic analgesic structurally related to METHADONE. Only the dextro-isomer has an analgesic effect; the levo-isomer appears to exert an antitussive effect.
A synthetic diphenyl propionate derivative structurally related to methadone, Propoxyphene Napsylate acts as a central narcotic and analgesic agent by interaction with mu opioid receptors, but with less selectivity then morphine. The dextro-isomer has analgesic effect, while the levo-isomer exerts an antitussive effect. The napsylate salt allows better dosage formulation than the hydrochloride salt. (NCI04)
A synthetic, nonselective beta-adrenergic receptor blocker with antianginal, antiarrhythmic, antihypertensive properties. Propranolol competitively antagonizes beta-adrenergic receptors, thereby causing negative chronotropic and inotropic effects leading to a reduction in cardiac output.
Antioxidant for foods, fats, oils, ethers, emulsions, waxes, and transformer oils.
An analog of benzilylcholine mustard. It is an alkylating nitrogen mustard analog that binds specifically and irreversibly to cholinergic muscarinic receptors and is used as an affinity label to isolate and study the receptors.
A propylamine derivative with sympathomimetic property. Propylhexedrine binds to and activates alpha-adrenergic receptors in the mucosa of the respiratory tract, thereby mimicking the actions of norepinephrine and epinephrine. This results in vasoconstriction and reduces swelling and inflammation of the mucous membrane lining, therefore relieving nasal and sinus congestion.
A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)
A cardiotonic glycoside isolated from Scilla maritima var. alba (Squill).
An antineoplastic dispiropiperazine derivative.
Compounds that inhibit the action of prostaglandins.
A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.
(13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15-hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE; PGA(1) and PGA(2) as well as their 19-hydroxy derivatives are found in many organs and tissues.
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).
Any synthetic agent that is chemically identical or similar to any of the naturally occurring prostaglandin subtypes.
A non-neoplastic or neoplastic disorder that affects the prostate gland. Representative examples include prostatitis, prostatic intraepithelial neoplasia, and carcinoma.
A benign, borderline, or malignant neoplasm that affects the prostate gland. Representative examples include benign prostate phyllodes tumor, prostatic intraepithelial neoplasia, prostate carcinoma, and prostate sarcoma.
An infectious or non-infectious inflammatory process affecting the prostate gland.
A heparin assay is a device used to determine the level of the anticoagulant heparin in the patient's circulation. These assays are quantitative clotting time procedures using the effect of heparin on activated coagulation factor X (Stuart factor) or procedures based on the neutralization of heparin by protamine sulfate (a protein that neutralizes heparin).
A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692)
Any substance that inhibits a protease, an enzyme that breaks peptide bonds. Proteases are required for many cell processes and inhibition of proteases can inhibit viral replication, inflammatory responses, proliferation, and tumor growth.
A class of agents used in prophylactic or curative therapy to attenuate the negative side effects of toxins or drugs. Protective agents belong to various chemical classes, acting through various pharmacological mechanisms. They may neutralize exogenous poisons, coat mucosa for protection against physical or chemical damage, offer antioxidant protection against free radicals or ionizing radiation, or induce endogenous detoxifying enzymes. (NCI04)
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.
A nutritional condition produced by a deficiency of proteins in the diet, characterized by adaptive enzyme changes in the liver, increase in amino acid synthetases, and diminution of urea formation, thus conserving nitrogen and reducing its loss in the urine. Growth, immune response, repair, and production of enzymes and hormones are all impaired in severe protein deficiency. Protein deficiency may also arise in the face of adequate protein intake if the protein is of poor quality (i.e., the content of one or more amino acids is inadequate and thus becomes the limiting factor in protein utilization). (From Merck Manual, 16th ed; Harrison's Principles of Internal Medicine, 12th ed, p406)
Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.
The enzymatic processing of a polypeptide chain after translation from messenger RNA and after peptide bond formation has occurred. Examples include glycosylation, acylation, limited proteolysis, phosphorylation, isoprenylation.
A pharmacological agent that inhibits the protein translation process. Protein synthesis inhibitors may be used therapeutically as antibacterial or bacteriostatic agents.
Detection of protein in a location it should not normally be present
A nutritional deficit that is caused by inadequate protein or calorie intake.
Abnormal loss of protein from the digestive tract related to excessive leakage of plasma proteins into the lumen of the gastrointestinal tract.
Increased levels of protein in the urine.
Infections with bacteria of the genus PROTEUS.
A thioamide derivative with antitubercular activity. Protionamide forms a covalent adduct with bacterial nicotinamide adenine dinucleotide (NAD), PTH-NAD, which competitively inhibits 2-trans-enoyl-ACP reductase (inhA), an enzyme essential for mycolic acid synthesis. This results in increased cell wall permeability and decreased resistance against cell injury eventually leading to cell lysis. Mycolic acids, long-chain fatty acids, are essential mycobacterial cell wall components and play a key role in resistance to cell injury and mycobacterial virulence.
A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.
Mixtures of closely related hypotensive alkaloids from Veratrum album (Liliaceae). They have been used in the treatment of hypertension but have largely been replaced by drugs with fewer adverse effects.
An infection that is caused by protozoans.
Infections with unicellular organisms formerly members of the subkingdom Protozoa. The infections may be experimental or veterinary.
Tricyclic antidepressant similar in action and side effects to IMIPRAMINE. It may produce excitation.
In its rare complete form, 'prune belly' syndrome comprises megacystis (massively enlarged bladder) with disorganized detrusor muscle, cryptorchidism, and thin abdominal musculature with overlying lax skin (summary by Weber et al., 2011).
A name applied to several itchy skin eruptions of unknown cause. The characteristic course is the formation of a dome-shaped papule with a small transient vesicle on top, followed by crusting over or lichenification. (From Dorland, 27th ed)
A skin disorder characterized by an intense itching sensation.
Intense chronic itching in the anal area.
Intense itching of the external female genitals.
A pathologic entity characterized by a developmental defect in a long bone leading to bending and pathologic fracture, with inability to form a normal bony callus with subsequent fibrous nonunion, leading to the pseudarthrosis (or ""false joint"").
Mucolipidosis alpha/beta (ML III alpha/beta; pseudo-Hurler polydystrophy), a slowly progressive disorder with clinical onset at approximately age three years, is characterized by slow growth rate and subnormal stature; radiographic evidence of mild to moderate dysostosis multiplex; joint stiffness and pain initially in the shoulders, hips, and fingers; gradual mild coarsening of facial features; and normal to mildly impaired cognitive development. If present, organomegaly is mild. Pain from osteoporosis that is clinically and radiologically apparent in childhood becomes more severe from adolescence. Cardiorespiratory complications (restrictive lung disease, thickening and insufficiency of the mitral and aortic valves, left and/or right ventricular hypertrophy) are common causes of death, typically in early to middle adulthood.
A condition affecting cranial nerves IX-XII resulting from upper motor neuron damage arising from a variety of causes.
Dementia-like disorder in the absence of organic brain disease.
A phenethylamine and a diastereomer of ephedrine with sympathomimetic property. Pseudoephedrine displaces norepinephrine from storage vesicles in presynaptic neurones, thereby releasing norepinephrine into the neuronal synapses where it stimulates primarily alpha-adrenergic receptors. It also has weak direct agonist activity at alpha- and beta- adrenergic receptors. Receptor stimulation results in vasoconstriction and decreases nasal and sinus congestion.
An acute episode of pain, swelling, and redness, sometimes associated with fever. It is caused by the deposition of calcium pyrophosphate crystals in the joints.
A condition consisting of possessing the internal reproductive organs of one sex while exhibiting some of the secondary sex characteristics of the opposite sex.
A heterogeneous group of disorders characterized by renal electrolyte transport dysfunctions. Congenital forms are rare autosomal disorders characterized by neonatal hypertension, HYPERKALEMIA, increased RENIN activity and ALDOSTERONE concentration. The Type I features HYPERKALEMIA with sodium wasting; Type II, HYPERKALEMIA without sodium wasting. Pseudohypoaldosteronism can be the result of a defective renal electrolyte transport protein or acquired after KIDNEY TRANSPLANTATION.
A condition characterized by resistance to the action of parathyroid hormone, in which there is hypocalcemia, hyperphosphatemia, and (appropriately) high levels of parathyroid hormone.
Infections with bacteria of the genus PSEUDOMONAS.
A usually well differentiated mucinous adenocarcinoma of the peritoneum. The majority of cases represent tumor spread from a primary low grade mucinous neoplasm of the appendix. Cases of pseudomyxoma peritonei associated with mucinous adenocarcinomas of the gallbladder, stomach, colon, rectum, pancreas, lung, breast, and fallopian tubes have also been reported. In the past, the ovary has been considered as a common primary site associated with pseudomyxoma peritonei. However, there is recent evidence based on immunohistochemistry and molecular genetic analysis suggesting that most cases of pseudomyxoma peritonei probably represent metastasis from an appendiceal and not ovarian primary.
Disorders of GNAS inactivation include the phenotypes pseudohypoparathyroidism Ia, Ib, and Ic (PHP-Ia, -Ib, -Ic), pseudopseudohypoparathyroidism (PPHP), progressive osseous heteroplasia (POH), and osteoma cutis (OC). PHP-Ia and PHP-Ic are characterized by: End-organ resistance to endocrine hormones including parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), gonadotropins (LH and FSH), growth hormone-releasing hormone (GHRH), and CNS neurotransmitters (leading to obesity and variable degrees of intellectual disability and developmental delay); and The Albright hereditary osteodystrophy (AHO) phenotype (short stature, round facies, and subcutaneous ossifications) and brachydactyly type E (shortening mainly of the 4th and/or 5th metacarpals and metatarsals and distal phalanx of the thumb). Although PHP-Ib is characterized principally by PTH resistance, some individuals also have partial TSH resistance and mild features of AHO (e.g., brachydactyly). PPHP, a more limited form of PHP-Ia, is characterized by various manifestations of the AHO phenotype without the hormone resistance or obesity. POH and OC are even more restricted variants of PPHP: POH consists of dermal ossification beginning in infancy, followed by increasing and extensive bone formation in deep muscle and fascia. OC consists of extra-skeletal ossification that is limited to the dermis and subcutaneous tissues.
A chronic, benign, inflammatory condition that is characterized by the swelling of lymph node in the head and neck.
A highly contagious herpesvirus infection affecting the central nervous system of swine, cattle, dogs, cats, rats, and other animals.
A condition marked by raised intracranial pressure and characterized clinically by HEADACHES; NAUSEA; PAPILLEDEMA, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile TINNITUS. OBESITY is frequently associated with this condition, which primarily affects women between 20 and 44 years of age. Chronic PAPILLEDEMA may lead to optic nerve injury (see OPTIC NERVE DISEASES) and visual loss (see BLINDNESS).
Pseudoxanthoma elasticum (PXE) is a systemic disorder that affects the elastic tissue of the skin, the eye, and the cardiovascular and gastrointestinal systems. Individuals most commonly present with papules in the skin and/or with angioid streaks of the retina found on routine eye examination or associated with retinal hemorrhage. Rarely, individuals may present with vascular signs and symptoms, such as gastrointestinal bleeding, angina, or intermittent claudication. The most frequent cause of morbidity and disability in PXE is reduced vision from macular hemorrhage and disciform scarring of the macula. Most affected individuals live a normal life span.
A tryptamine alkaloid, isolated from various genera of fungi including the genus Psilocybe, with hallucinogenic, anxiolytic, and psychoactive activities. In vivo, psilocybine is rapidly dephosphorylated into the active compound psilocin, which activates serotonin 2A (5-HT2A) receptors in the central nervous system (CNS), mimicking the effects of serotonin.
A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.
A common primary headache disorder, characterized by a dull, non-pulsatile, diffuse, band-like (or vice-like) PAIN of mild to moderate intensity in the HEAD; SCALP; or NECK. The subtypes are classified by frequency and severity of symptoms. There is no clear cause even though it has been associated with MUSCLE CONTRACTION and stress. (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)
Abnormalities of motor function that are associated with organic and non-organic cognitive disorders.
A group of disorders characterized by physical symptoms that are affected by emotional factors and involve a single organ system, usually under AUTONOMIC NERVOUS SYSTEM control. (American Psychiatric Glossary, 1988)
A group of mental disorders associated with organic brain damage and caused by poisoning from alcohol.
Psychotic organic mental disorders resulting from the toxic effect of drugs and chemicals or other harmful substance.
The stages of development of the psychological aspects of sexuality from birth to adulthood; i.e., oral, anal, genital, and latent periods.
The persistent of recurrent difficulty, delay in, or absence of attaining orgasm following sufficient sexual stimulation and arousal.
Persistent delay or absence in orgasm not accounted for by a medical reason.
Recurrent and persistent suppression of sexual excitement during sexual activity.
Disturbances in sexual desire and the psychophysiologic changes that characterize the sexual response cycle and cause marked distress and interpersonal difficulty. (APA, DSM-IV, 1994)
A disorder characterized by delusions, hallucinations, disorganized speech, and/or grossly disorganized behavior that resolve within a month.
A condition characterized by changes of personality and thought patterns often accompanied by hallucinations and delusional beliefs.
A classification of medication that acts on the central nervous system, affecting brain function, level of consciousness, mood, emotions, and behavior.
Dried, ripe seeds of PLANTAGO PSYLLIUM; PLANTAGO INDICA; and PLANTAGO OVATA. Plantain seeds swell in water and are used as demulcents and bulk laxatives.
Compounds based on pyrazino[2,3-d]pyrimidine which is a pyrimidine fused to a pyrazine, containing four NITROGEN atoms.
An abnormal triangular fold of membrane in the interpalpebral fissure, extending from the conjunctiva to the cornea, being immovably united to the cornea at its apex, firmly attached to the sclera throughout its middle portion, and merged with the conjunctiva at its base. (Dorland, 27th ed)
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.
Development of SEXUAL MATURATION in boys and girls at a chronological age that is 2.5 standard deviations below the mean age at onset of PUBERTY in the population. This early maturation of the hypothalamic-pituitary-gonadal axis results in sexual precocity, elevated serum levels of GONADOTROPINS and GONADAL STEROID HORMONES such as ESTRADIOL and TESTOSTERONE.
Disorders or diseases associated with PUERPERIUM, the six-to-eight-week period immediately after PARTURITION in humans.
An infection occurring in PUERPERIUM, the period of 6-8 weeks after giving birth.
A contagious, neoplastic, pulmonary disease of sheep characterized by hyperplasia and hypertrophy of pneumocytes and epithelial cells of the lung. It is caused by JAAGSIEKTE SHEEP RETROVIRUS.
A PULMONARY ALVEOLI-filling disease, characterized by dense phospholipoproteinaceous deposits in the alveoli, cough, and DYSPNEA. This disease is often related to, congenital or acquired, impaired processing of PULMONARY SURFACTANTS by alveolar macrophages, a process dependent on GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR.
The amount of a gas taken up, by the pulmonary capillary blood from the alveolar gas, per minute per unit of average pressure of the gradient of the gas across the BLOOD-AIR BARRIER.
Accumulation of fluid in the lung tissues causing disturbance of the gas exchange that may lead to respiratory failure. It is caused by direct injury to the lung parenchyma or congestive heart failure. The symptoms may appear suddenly or gradually. Suddenly appearing symptoms include difficulty breathing, feeling of suffocation, and coughing associated with frothy sputum. Gradually appearing symptoms include difficulty breathing while lying in bed, shortness of breath during activity, and weight gain (in patients with congestive heart failure).
An embolus (that is, an abnormal particle circulating in the blood) located in the pulmonary artery and thereby blocking blood circulation to the lung. Usually the embolus is a blood clot that has developed in an extremity (for instance, a deep venous thrombosis), detached, and traveled through the circulation before becoming trapped in the pulmonary artery.
A subcategory of chronic obstructive pulmonary disease (COPD). It occurs in people who smoke and suffer from chronic bronchitis. It is characterized by inflation of the alveoli, alveolar wall damage, and reduction in the number of alveoli, resulting in difficulty breathing.
A condition characterized by infiltration of the lung with EOSINOPHILS due to inflammation or other disease processes. Major eosinophilic lung diseases are the eosinophilic pneumonias caused by infections, allergens, or toxic agents.
A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.
Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.
Localized necrosis of lung tissue caused by obstruction of the arterial blood supply, most often due to pulmonary embolism.
A benign or malignant small, oval or round growth in the lung. It can be due to infectious, inflammatory or neoplastic processes.
Narrowing below the PULMONARY VALVE or well below it in the infundibuluar chamber where the pulmonary artery originates, usually caused by a defective VENTRICULAR SEPTUM or presence of fibrous tissues. It is characterized by restricted blood outflow from the RIGHT VENTRICLE into the PULMONARY ARTERY, exertional fatigue, DYSPNEA, and chest discomfort.
Pulmonary surfactant lines the lung epithelium and lowers surface tension to prevent collapse at end-expiration. Deficiency of pulmonary surfactant results in respiratory distress syndrome (RDS) in premature infants. Lung surfactant is synthesized in alveolar type II cells, stored in lamellar bodies and secreted via exocytosis.
A heart disorder characterized by a defect in pulmonary valve structure or function.
Backflow of blood from the PULMONARY ARTERY into the RIGHT VENTRICLE due to imperfect closure of the PULMONARY VALVE.
The pathologic narrowing of the orifice of the PULMONARY VALVE. This lesion restricts blood outflow from the RIGHT VENTRICLE to the PULMONARY ARTERY. When the trileaflet valve is fused into an imperforate membrane, the blockage is complete.
A disorder characterized by pulmonary venous constriction or occlusion, resulting in pulmonary hypertension.
Deterioration of the normal pulp tissue.
Inflammation of the DENTAL PULP, usually due to bacterial infection in dental caries, tooth fracture, or other conditions causing exposure of the pulp to bacterial invasion. Chemical irritants, thermal factors, hyperemic changes, and other factors may also cause pulpitis.
Conditions which affect the structure or function of the pupil of the eye, including disorders of innervation to the pupillary constrictor or dilator muscles, and disorders of pupillary reflexes.
Purines with a RIBOSE attached that can be phosphorylated to PURINE NUCLEOTIDES.
Dysfunctions in the metabolism of PURINES or PYRIMIDINES resulting from inborn genetic mutations that are inherited or acquired in utero.
A small blood vessel hemorrhage into the skin and/or mucous membranes. Newer lesions appear reddish in color. Older lesions are usually a darker purple color and eventually become a brownish-yellow color.
Purplish or brownish red discoloration of the skin associated with increase in circulating polyclonal globulins, usually GAMMA-GLOBULINS. This syndrome often occurs on the legs of women aged 20 to 40 years.
A systemic non-thrombocytopenic purpura caused by HYPERSENSITIVITY VASCULITIS and deposition of IGA-containing IMMUNE COMPLEXES within the blood vessels throughout the body, including those in the kidney (KIDNEY GLOMERULUS). Clinical symptoms include URTICARIA; ERYTHEMA; ARTHRITIS; GASTROINTESTINAL HEMORRHAGE; and renal involvement. Most cases are seen in children after acute upper respiratory infections.
a condition where platelets are used to form blood clots within the circulation thus causes low platelets and high bleeding tendency
A coagulation disorder characterized by extensive formation of thrombi in small blood vessels throughout the body due to low levels of ADAMTS13 protein, and resulting in consumption of circulating platelets, which is characterized by thrombocytopenia, anemia, neurologic changes, and sometimes fever and renal dysfunction.
Inflammation of the KIDNEY PELVIS and KIDNEY CALICES where urine is collected before discharge, but does not involve the renal parenchyma (the NEPHRONS) where urine is processed.
Inflammation of the KIDNEY PELVIS and the URINARY BLADDER.
An inflammation of the kidney involving the parenchyma of kidney, the renal pelvis and the kidney calices.
A chronic inflammatory condition of the KIDNEY resulting in diffuse renal destruction, a grossly enlarged and nonfunctioning kidney associated with NEPHROLITHIASIS and KIDNEY STONES.
Septicemia caused by pyogenic microorganisms (e.g., STAPHYLOCOCCUS; BACILLUS), resulting in the formation of secondary foci of SUPPURATION and multiple ABSCESSES.
Any manifestation of a skin disease associated with the production of pus.
A lobular hemangioma arising from the skin and attached subcutaneous tissues.
An accumulation of PUS in the uterine cavity (UTERUS). Pyometra generally indicates the presence of infections.
Distention of KIDNEY with the presence of PUS and suppurative destruction of the renal parenchyma. It is often associated with renal obstruction and can lead to total or nearly total loss of renal function.
The presence of pus in the fallopian tube. It is usually caused by acute salpingitis. The fallopian tube is distended and filled with pus. Histologic examination reveals edema and acute and chronic inflammation. Symptoms include fever, vaginal discharge, and pelvic pain.
An abscess that is located in the ureter.
Copolymer of divinyl ether and maleic anhydride that acts as an immunostimulant with antineoplastic and anti-infective properties. It is used in combination with other antineoplastic agents.
A depolarizing neuromuscular-blocking agent, that causes persistent nicotinic activation resulting in spastic paralysis of susceptible nematodes. It is a drug of second-choice after benzimidazoles for treatment of ascariasis, hookworm, and pinworm infections, being effective after a single dose. (From Smith and Reynard, Textbook of Pharmacology, 1992, p920)
Broad spectrum antinematodal anthelmintic used also in veterinary medicine.
Broad spectrum anthelmintic for livestock.
A pyrazine that is used therapeutically as an antitubercular agent.
A class of heterocyclic organic compounds characterized by a ring structure composed of three carbon atoms and two nitrogen atoms in adjacent positions. Derivatives of pyrazole exhibit a variety of pharmacological properties, including anti-inflammatory, anti-psychotic, antibiotic and antineoplastic.
A drug that has been given by mouth in the treatment of atherosclerosis and other vascular disorders, hyperlipidemias, and thrombo-embolic disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1408)
A cholinesterase inhibitor with a slightly longer duration of action than NEOSTIGMINE. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.
The 4-carboxyaldehyde form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid.
The active form of vitamin B6 and a coenzyme for many pyridoxal phosphate (PLP)-dependent enzymes. PLP is involved in numerous enzymatic transamination, decarboxylation and deamination reactions; it is necessary for the synthesis of amino acids and amino acid metabolites, and for the synthesis and/or catabolism of certain neurotransmitters, including the conversion of glutamate into gamma-aminobutyric acid (GABA) and levodopa into dopamine. PLP can be used as a dietary supplement in cases of vitamin B6 deficiency. Reduced levels of PLP in the brain can cause neurological dysfunction.
The 4-aminomethyl form of VITAMIN B 6. During transamination of amino acids, PYRIDOXAL PHOSPHATE is transiently converted into pyridoxamine phosphate.
The 4-methanol form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).
A histamine H1 antagonist. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies.
A synthetic derivative of ethyl-pyrimidine with potent antimalarial properties. Pyrimethamine is a competitive inhibitor of dihydrofolate reductase (DHFR). DHFR is a key enzyme in the redox cycle for production of tetrahydrofolate, a cofactor that is required for the synthesis of DNA and proteins. This agent is often used in combination with other antimalarials for the treatment of uncomplicated falciparum malaria. (NCI04)
A thiamine antagonist due to its inhibition of thiamine pyrophosphorylation. It is used to produce thiamine deficiency.
A neurotropic agent which reduces permeability of blood-brain barrier to phosphate. It has no vitamin B6 activity.
A trihydroxybenzene or dihydroxy phenol that can be prepared by heating GALLIC ACID.
Inorganic salts of phosphoric acid that contain two phosphate groups.
A pyrrole antifungal agent isolated from several Pseudomonas species. Pyrrolnitrin interrupts the terminal electron transport system and inhibits cellular respiration. This agent has activity against dermatophytic fungi, especially species of Trichophyton.
Pyruvate carboxylase (PC) deficiency is characterized in most affected individuals by failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis. Three clinical types are recognized: Type A (infantile form), in which most affected children die in infancy or early childhood. Type B (severe neonatal form), in which affected infants have hepatomegaly, pyramidal tract signs, and abnormal movement and die within the first three months of life. Type C (intermittent/benign form), in which affected individuals have normal or mildly delayed neurologic development and episodic metabolic acidosis.
A genetic disorder caused by mutations in the genes that are responsible for production of protein components of the pyruvate dehydrogenase complex. It may present with lactic acidosis. Signs and symptoms include developmental delays, seizures and hypotonia.
Hereditary disorders of pyruvate metabolism. They are difficult to diagnose and describe because pyruvate is a key intermediate in glycolysis, gluconeogenesis, and the tricarboxylic acid cycle. Some inherited metabolic disorders may alter pyruvate metabolism indirectly. Disorders in pyruvate metabolism appear to lead to deficiencies in neurotransmitter synthesis and, consequently, to nervous system disorders.
Presence of an increased number of neutrophils in the urine.
A bacterial infection caused by Coxiella burnetii. It is transmitted to humans by the inhalation of infected air particles or contact with fluids and feces of infected animals. Signs and symptoms include the abrupt onset of fever, headache, myalgias, and weakness.
Paralysis of all four limbs, and trunk of the body below the level of an associated injury to the spinal cord. The etiology of quadriplegia is similar to that of paraplegia except that the lesion is in the cervical spinal cord rather than in the thoracic or lumbar segments of the spinal cord.
A flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin.
An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.
The 3-cyclopentyl ether of ETHINYL ESTRADIOL. After gastrointestinal absorption, it is stored in ADIPOSE TISSUE, slowly released, and metabolized principally to the parent compound. It has been used in ESTROGEN REPLACEMENT THERAPY. (From AMA Drug Evaluations Annual, 1992, p1011)
An acid which is found in cinchona bark and elsewhere in plants. (From Stedman, 26th ed)
An alkaloid extracted from the bark of the Cinchona tree with class 1A antiarrhythmic and antimalarial effects. Quinidine stabilizes the neuronal membrane by binding to and inhibiting voltage-gated sodium channels, thereby inhibiting the sodium influx required for the initiation and conduction of impulses resulting in an increase of the threshold for excitation and decreased depolarization during phase 0 of the action potential. In addition, the effective refractory period (ERP), action potential duration (APD), and ERP/APD ratios are increased, resulting in decreased conduction velocity of nerve impulses. Quinidine exerts its antimalarial activity by acting primarily as an intra-erythrocytic schizonticide through association with the heme polymer (hemazoin) in the acidic food vacuole of the parasite thereby preventing further polymerization by heme polymerase enzyme. This results in accumulation of toxic heme and death of the parasite.
The sulfate salt form of quinidine, an alkaloid with antimalarial and antiarrhythmic (Class la) properties. Quinidine sulfate exerts its anti-malarial activity by acting primarily as an intra-erythrocytic schizonticide through association with the hemepolymer (hemozoin) in the acidic food vacuole of the parasite thereby preventing further polymerization by heme polymerase enzyme. This results in accumulation of toxic heme and death of the parasite. Quinidine sulfate exerts its antiarrhythmic effects by depressing the flow of sodium ions into cells during phase 0 of the cardiac action potential, thereby slowing the impulse conduction through the atrioventricular (AV) node, reducing the rate of phase 0 depolarization and prolonging the refractory period. Quinidine sulfate also reduces the slope of phase 4 depolarization in Purkinje-fibres resulting in slowed conduction and reduced automaticity in the heart.
A quinidine alkaloid isolated from the bark of the cinchona tree. Quinine has many mechanisms of action, including reduction of oxygen intake and carbohydrate metabolism; disruption of DNA replication and transcription via DNA intercalation; and reduction of the excitability of muscle fibers via alteration of calcium distribution. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents. (NCI04)
The sulfate salt form of the quinidine alkaloid isolate quinine. Quinine has many mechanisms of action, including reduction of oxygen intake and carbohydrate metabolism; disruption of DNA replication and transcription via DNA intercalation; and reduction of the excitability of muscle fibers via alteration of calcium distribution. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents. (NCI04)
A high-affinity muscarinic antagonist commonly used as a tool in animal and tissue studies.
A piperazine-based nonselective serotonin (5-HT) receptor agonist with antidepressant and oxytocic activities. Quipazine targets and binds to serotonin receptors, particularly to the 5HT2A and 5HT3 receptors. Serotonin receptor activation by quipazine may lead to smooth muscle contraction and antidepressant effects.
A life-threatening viral infection caused by the neurotropic Rabies virus. It is transmitted to humans usually from a bite by an infected dog. The initial signs and symptoms include malaise, fever, and headache, followed by the central nervous system manifestations which include abrupt behavioral changes. Paralysis, lethargy, and coma follow the behavioral changes.
Vaccines or candidate vaccines used to prevent and treat RABIES. The inactivated virus vaccine is used for preexposure immunization to persons at high risk of exposure, and in conjunction with rabies immunoglobulin, for postexposure prophylaxis.
A preparation of METHIONINE that includes a mixture of D-methionine and L-methionine isomers.
A pharmacological agent that protects the recipient from the damage that may result from exposure to ionizing radiation.
An agent that makes tumor cells more sensitive to radiation therapy.
Radiolucency (reflecting a reduction in the bony substance) around the apex (the tip of the dental root).
An inflammatory process affecting a nerve root. Patients experience pain radiating along a nerve path because of spinal pressure on the nerve root that connects to the nerve path.
A radioactive element of the alkaline earth series of metals. It has the atomic symbol Ra and atomic number 88. Radium is the product of the disintegration of URANIUM and is present in pitchblende and all ores containing uranium. It is used clinically as a source of beta and gamma-rays in radiotherapy, particularly BRACHYTHERAPY.
Veterinary anthelmintic for grazing animals; used to treat fluke, hookworm and other infestations.
Abnormal breath sounds (crackles) heard on auscultation, indicating inflammation, fluid, or infection of the lung.
A member of the class of histamine H2-receptor antagonists with antacid activity. Ranitidine is a competitive and reversible inhibitor of the action of histamine, released by enterochromaffin-like (ECL) cells, at the histamine H2-receptors on parietal cells in the stomach, thereby inhibiting the normal and meal-stimulated secretion of stomach acid. In addition, other substances that promote acid secretion have a reduced effect on parietal cells when the H2 receptors are blocked.
A syndrome characterized by recurring fever, rash, and arthralgias occurring days to weeks after a rat bite. The causative agents are either Streptobacillus moniliformis or Spirillum minus.
Raynaud phenomenon is a condition in which the body's normal response to cold or emotional stress is exaggerated, resulting in abnormal spasms (vasospasms) in small blood vessels called arterioles. The disorder mainly affects the fingers but can also involve the ears, nose, nipples, knees, or toes. The vasospasms reduce blood circulation, leading to discomfort and skin color changes.Raynaud phenomenon is episodic, meaning that it comes and goes. A typical episode lasts about 15 minutes after the cold exposure or stressor has ended and involves mild discomfort such as numbness or a feeling of ""pins and needles."" The affected areas usually turn white or blue when exposed to cold or when emotional stress occurs, and then turn red when re-warmed or when the stress eases.Raynaud phenomenon is categorized as primary when there is no underlying disorder that accounts for the exaggerated response of the blood vessels. It is called secondary when it is associated with another condition. Secondary Raynaud phenomenon is often associated with autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own tissues and organs. Autoimmune disorders with which Raynaud phenomenon can be associated include systemic lupus erythematosus, scleroderma, rheumatoid arthritis, and Sjögren syndrome.Primary Raynaud phenomenon is much more common and usually less severe than secondary Raynaud phenomenon. In severe cases of secondary Raynaud phenomenon, sores on the pads of the fingers or tissue death (necrosis) can occur. Primary Raynaud phenomenon often begins between the ages of 15 and 25, while secondary Raynaud phenomenon usually starts after age 30. Some people with Raynaud phenomenon alone later go on to develop another associated condition; regardless of which comes first, these cases are classified as secondary Raynaud phenomenon.
An episodic vasoconstriction resulting in discoloration of the skin and pain in the affected areas, often involving fingers or toes. Classically associated with triphasic color changes (white, blue, red) but may be biphasic. Often occurs in response to cold temperatures or emotional stress. May be primary or secondary to an underlying autoimmune disease.
An antimitotic agent with immunosuppressive properties.
A condition in which the failure to establish healthy bonds with caregivers in early childhood leads to lifelong impairment of social interactions.
Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.
A disorder in which an individual has an abnormally low noise tolerance, and increased sensitivity to sounds.
Pathological developments in the RECTUM region of the large intestine (INTESTINE, LARGE).
An abnormal anatomical passage connecting the RECTUM to the outside, with an orifice at the site of drainage.
A benign or malignant neoplasm that affects the rectum. Representative examples of benign neoplasms include lipoma and leiomyoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma. Rectal adenomas always exhibit epithelial dysplasia and are considered premalignant neoplasms.
A polypoid lesion that arises from the rectum and protrudes into the lumen. This group includes adenomatous polyps, serrated polyps, and hamartomatous polyps.
Protrusion of the rectal mucous membrane through the anus.
An abnormal anatomical passage between the RECTUM and the VAGINA.
A disease characterized by normocytic, normochromic anemia, low hematocrit, reticulocytopenia, and selective erythroid hypoplasia.
A neurologic condition characterized by burning pain, tenderness, swelling, and changes in the skin color and temperature of a body part or extremity that has no identifiable nerve injury; most pediatric patients present with this form.
An abnormal response to a stimulus applied to the sensory components of the nervous system. This may take the form of increased, decreased, or absent reflexes.
A reflex characterized by upward movement of the great toe and an outward movement of the rest of the toes, when the sole of the foot is stroked. It is a normal reflex up to the age of two. Its presence beyond that age indicates neurological damage.
A defect in the focusing of light on the retina as in astigmatism, myopia, or hyperopia.
Refsum disease is characterized by anosmia and early-onset retinitis pigmentosa, which are both universal findings with variable combinations of neuropathy, deafness, ataxia, and ichthyosis. Onset of symptoms ranges from age seven months to older than age 50 years. Cardiac arrhythmia and heart failure caused by cardiomyopathy are potentially severe health problems which develop later in life.
GASTROESOPHAGEAL REFLUX wherein the retrograde flow passes through the UPPER ESOPHAGEAL SPHINCTER
Fluids restored to the body in order to maintain normal water-electrolyte balance.
A rare, reactive inflammatory disorder seen following bacterial infection. It predominantly affects males aged 20-40. Individuals with HLA-B27 antigen are estimated to have a 50 % increased risk. The disorder is characterized by arthritis, conjunctivitis, uveitis, iritis and ulceration of the oral cavity, genitals and volar surfaces of the hands and feet. The clinical course is self-limited with resolution of clinical disease usually within six months of onset.
An acute infection characterized by recurrent episodes of PYREXIA alternating with asymptomatic intervals of apparent recovery. This condition is caused by SPIROCHETES of the genus BORRELIA. It is transmitted by the BITES of either the body louse (PEDICULUS humanus corporis), for which humans are the reservoir, or by soft ticks of the genus ORNITHODOROS, for which rodents and other animals are the principal reservoirs.
An infection that is caused by certain species of Rickettsia or Borrelia, which are transmitted to humans from infected ticks; it is characterized by sudden fever, chills, headaches, myalgia, arthralgia, nausea, and possibly a rash. Symptoms usually persist for two to nine days, then disappear, with recurrence after several weeks if the patient remains untreated.
A water-soluble polypeptide (molecular weight approximately 8,000) extractable from the corpus luteum of pregnancy. It produces relaxation of the pubic symphysis and dilation of the uterine cervix in certain animal species. Its role in the human pregnant female is uncertain. (Dorland, 28th ed)
Drugs used for their effects on the kidneys' regulation of body fluid composition and volume. The most commonly used are the diuretics. Also included are drugs used for their antidiuretic and uricosuric actions, for their effects on the kidneys' clearance of other drugs, and for diagnosis of renal function.
Narrowing or occlusion of the RENAL ARTERY or arteries. It is due usually to ATHEROSCLEROSIS; FIBROMUSCULAR DYSPLASIA; THROMBOSIS; EMBOLISM, or external pressure. The reduced renal perfusion can lead to renovascular hypertension (HYPERTENSION, RENOVASCULAR).
Narrowing of a main artery in the kidney.
A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism.
Ischemic necrosis of the kidney caused by interruption of the blood supply to the area.
Abnormalities of bone mineral metabolism associated with chronic kidney disease.
Genetic defects in the selective or non-selective transport functions of the KIDNEY TUBULES.
Infections produced by reoviruses, general or unspecified.
Harmful and painful condition caused by overuse or overexertion of some part of the musculoskeletal system, often resulting from work-related physical activities. It is characterized by inflammation, pain, or dysfunction of the involved joints, bones, ligaments, and nerves.
Substances used either in the prevention or facilitation of pregnancy.
An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.
A water-soluble crystalline benzene-1,3-diol (resorcinol) and its derivatives.
A non-neoplastic or neoplastic disorder that affects the respiratory system. Representative examples include pneumonia, chronic obstructive pulmonary disease, pulmonary failure, lung adenoma, lung carcinoma, and tracheal carcinoma.
The total volume of gas inspired or expired per unit of time, usually measured in liters per minute.
A condition beginning in the first day of life that results from inadequate surfactant production, causing increased work of breathing and impaired gas exchange.
A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA.
A form of hypersensitivity affecting the respiratory tract. It includes ASTHMA and RHINITIS, ALLERGIC, SEASONAL.
Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)
Complete or severe weakness of the muscles of respiration. This condition may be associated with MOTOR NEURON DISEASES; PERIPHERAL NERVE DISEASES; NEUROMUSCULAR JUNCTION DISEASES; SPINAL CORD DISEASES; injury to the PHRENIC NERVE; and other disorders.
Infection with the respiratory syncytial virus, an RNA virus of the genus Pneumovirus, in the family Paramyxoviridae, which is characterized by the formation of syncytia in tissue culture. It causes minor respiratory infection with rhinitis and cough in adults, but is capable of causing severe bronchitis and bronchopneumonia in young children.
An abnormality of the respiratory system that is present at birth or detected in the neonatal period.
Diseases involving the RESPIRATORY SYSTEM.
An infection of the upper or lower respiratory tract.
A benign or malignant, primary or metastatic neoplasm involving the respiratory tract.
A condition that occurs while resting or lying in bed; it is characterized by an irresistible urgency to move the legs to obtain relief from a strange and uncomfortable sensation in the legs.
Variation occurring within a species in the length of DNA fragments generated by a specific endonuclease. Such variations are generated by mutations that create or abolish recognition sites for these enzymes.
A cyst that is formed because of the blockage of the duct of a glandular organ. This results in the retention of the glandular secretions.
A greater than normal number of blood cells in the reticuloendothelial system.
A rare cutaneous lesion composed of eosinophilic histiocytes, which are often multinucleated. The lesions are yellow-brown papules affecting any part of the body. Patients are usually adult men. The prognosis is excellent. -- 2003
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells.
Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).
An abnormal structure or function of the retina and its associated tissues.
Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium.
Congenital, often bilateral, retinal abnormality characterized by the arrangement of outer nuclear retinal cells in a palisading or radiating pattern surrounding a central ocular space. This disorder is sometimes hereditary.
Bleeding from the vessels of the retina.
Mild to fulminant necrotizing vaso-occlusive retinitis associated with a high incidence of retinal detachment and poor vision outcome.
In wound repair, neovascularization (NV) involves the sprouting of new vessels from pre-existent vessels to repair or replace damaged vessels. In the retina, NV is a response to ischemia. The NV adheres to the inner surface of the retina and outer surface of the vitreous. NV are deficient in tight junctions and hence leak plasma into surrounding tissue including the vitreous. Plasma causes the vitreous gel to degenerate, contract, and eventually collapse which pulls on the retina. Since retinal NV is adherent to both retina and vitreous, as the vitreous contracts the NV may be sheared resulting in vitreous hemorrhage or the NV may remain intact and pull the retina with the vitreous resulting in retinal elevation referred to as traction retinal detachment.
An occlusion of the retinal vasculature.
A carotenoid constituent of visual pigments. It is the oxidized form of retinol which functions as the active component of the visual cycle. It is bound to the protein opsin forming the complex rhodopsin. When stimulated by visible light, the retinal component of the rhodopsin complex undergoes isomerization at the 11-position of the double bond to the cis-form; this is reversed in ""dark"" reactions to return to the native trans-configuration.
Inflammation of the RETINA. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (CHORIORETINITIS) and of the OPTIC DISK (neuroretinitis).
Retinitis pigmentosa (RP) refers to a heterogeneous group of inherited ocular diseases that result in a progressive retinal degeneration affecting 1 in 3,000 to 5,000 people (Veltel et al., 2008). Symptoms include night blindness, the development of tunnel vision, and slowly progressive decreased central vision starting at approximately 20 years of age. Upon examination, patients have decreased visual acuity, constricted visual fields, dyschromatopsia (tritanopic; see 190900), and the classic fundus appearance with dark pigmentary clumps in the midperiphery and perivenous areas ('bone spicules'), attenuated retinal vessels, cystoid macular edema, fine pigmented vitreous cells, and waxy optic disc pallor. RP is associated with posterior subcapsular cataracts in 39 to 72% of patients, high myopia, astigmatism, keratoconus, and mild hearing loss in 30% of patients (excluding patients with Usher syndrome; see 276900). Fifty percent of female carriers of X-linked RP have a golden reflex in the posterior pole (summary by Kaiser et al., 2004). Juvenile Retinitis Pigmentosa Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (see 204000), whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). Autosomal recessive forms of juvenile retinitis pigmentosa can be caused by mutation in the SPATA7 (609868), LRAT (604863), and TULP1 (602280) genes (see LCA3, 604232, LCA14, 613341, and LCA15, 613843, respectively). An autosomal dominant form of juvenile retinitis pigmentosa (see 604393) is caused by mutation in the AIPL1 gene (604392).
Retinoblastoma is a malignant tumor of the developing retina that occurs in children, usually before age five years. Retinoblastoma develops from cells that have cancer-predisposing variants in both copies of RB1. Retinoblastoma may be unifocal or multifocal. About 60% of affected individuals have unilateral retinoblastoma with a mean age of diagnosis of 24 months; about 40% have bilateral retinoblastoma with a mean age of diagnosis of 15 months. Heritable retinoblastoma is an autosomal dominant susceptibility for retinoblastoma. Individuals with heritable retinoblastoma are also at increased risk of developing non-ocular tumors.
A group of agents that includes retinol (Vitamin A) and related compounds with potential antineoplastic and/or chemopreventive activities. A retinoic acid agent binds to and/or activates specific nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs), thereby modulating transcription of genes responsible for cell differentiation and proliferation. A retinoic acid agent may exhibit immunomodulatory and anti-inflammatory properties and may inhibit ornithine decarboxylase, resulting in a decrease in polyamine synthesis and keratinization. (NCI04)
A bilateral retinopathy characterized by neovascularization, scarring, retinal detachment, and eventually blindness. It may be mild or severe. It occurs in babies born prematurely. Causes include oxygen toxicity and hypoxia.
The state of being retired from one's position or occupation.
Pathological processes involving the VESTIBULOCOCHLEAR NERVE; BRAINSTEM; or CENTRAL NERVOUS SYSTEM. When hearing loss is due to retrocochlear pathology, it is called retrocochlear hearing loss.
The condition or state of a person suffering from retrognathia.
Pathologic changes that occur in the axon and cell body of a neuron proximal to an axonal lesion. The process is characterized by central chromatolysis which features flattening and displacement of the nucleus, loss of Nissl bodies, and cellular edema. Central chromatolysis primarily occurs in lower motor neurons.
A rare, serious disorder characterized by extensive fibrosis in the retroperitoneum. In most cases its etiology is unknown. In some cases it is related to autoimmunity or metastatic cancer. It leads to the entrapment and obstruction of vital retroperitoneal structures including the ureters.
A benign or malignant neoplasm that affects the retroperitoneum.
Virus diseases caused by the RETROVIRIDAE.
Rett syndrome is a neurodevelopmental disorder that occurs almost exclusively in females. It is characterized by arrested development between 6 and 18 months of age, regression of acquired skills, loss of speech, stereotypic movements (classically of the hands), microcephaly, seizures, and mental retardation. Rarely, classically affected males with somatic mosaicism or an extra X chromosome have been described (Moog et al., 2003).
A form of encephalopathy with fatty infiltration of the LIVER, characterized by brain EDEMA and VOMITING that may rapidly progress to SEIZURES; COMA; and DEATH. It is caused by a generalized loss of mitochondrial function leading to disturbances in fatty acid and CARNITINE metabolism.
The mother develops antibodies against red blood cell Rhesus antigens. This may lead to potential fetal adverse outcomes such as anemia.
A clinical syndrome resulting from direct or indirect muscle injury and subsequent release of myoglobin into the plasma.
A benign mesenchymal tumor arising from skeletal or cardiac muscle.
A malignant solid tumor arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites. It is divided into four distinct types: pleomorphic, predominantly in male adults; alveolar (RHABDOMYOSARCOMA, ALVEOLAR), mainly in adolescents and young adults; embryonal (RHABDOMYOSARCOMA, EMBRYONAL), predominantly in infants and children; and botryoidal, also in young children. It is one of the most frequently occurring soft tissue sarcomas and the most common in children under 15. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p2186; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1647-9)
Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.
A febrile disease occurring as a delayed sequela of infections with STREPTOCOCCUS PYOGENES. It is characterized by multiple focal inflammatory lesions of the connective tissue structures, such as the heart, blood vessels, and joints (POLYARTHRITIS) and brain, and by the presence of ASCHOFF BODIES in the myocardium and skin.
An autoinflammatory condition following an infection with Group A Beta Hemolytic Streptococcus (GABHS), in which the heart is attacked by antibodies formed in reaction to a recent GABHS infection. Chief anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords, all of which can result in valvular dysfunction.
Pancarditis, involving inflammation of the endocardium, myocardium, and epicardium. It results from an autoimmune reaction following an infection with Streptococcus pyogenes (Group A Streptococci).
A small round or oval, mostly subcutaneous nodule made up chiefly of a mass of Aschoff bodies and seen in cases of rheumatic fever. It is differentiated from the RHEUMATOID NODULE which appears in rheumatoid arthritis, most frequently over bony prominences. (From Dorland, 27th ed)
An inflammation of the mucous membrane lining the nose, usually associated with nasal discharge.
Allergic rhinitis caused by indoor allergens and lasting year round.
A chronic inflammation in which the NASAL MUCOSA gradually changes from a functional to a non-functional lining without mucociliary clearance. It is often accompanied by degradation of the bony TURBINATES, and the foul-smelling mucus which forms a greenish crust (ozena).
A form of non-allergic rhinitis that is characterized by nasal congestion and posterior pharyngeal drainage.
A manifestation of severe ROSACEA resulting in significant enlargement of the NOSE and occurring primarily in men. It is caused by hypertrophy of the SEBACEOUS GLANDS and surrounding CONNECTIVE TISSUE. The nose is reddened and marked with TELANGIECTASIS.
A granulomatous disease caused by KLEBSIELLA RHINOSCLEROMATIS infection. Despite its name, this disease is not limited to the nose and NASOPHARYNX but may affect any part of the RESPIRATORY TRACT, sometimes with extension to the lip and the skin.
Chronic, localized granulomatous infection of mucocutaneous tissues, especially the NOSE, and characterized by HYPERPLASIA and the development of POLYPS. It is found in humans and other animals and is caused by the mesomycetozoean organism RHINOSPORIDIUM SEEBERI.
Abnormal breath sounds characterized by low-pitched, snoring or rattle-like sounds.
A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses.
An essential human nutrient that is a heat-stable and water-soluble flavin belonging to the vitamin B family. Riboflavin is a precursor of the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These coenzymes are of vital importance in normal tissue respiration, pyridoxine activation, tryptophan to niacin conversion, fat, carbohydrate, and protein metabolism, and glutathione reductase mediated detoxification. Riboflavin may also be involved in maintaining erythrocyte integrity. This vitamin is essential for healthy skin, nails, and hair.
A dietary deficiency of riboflavin causing a syndrome chiefly marked by cheilitis, angular stomatitis, glossitis associated with a purplish red or magenta-colored tongue that may show fissures, corneal vascularization, dyssebacia, and anemia. (Dorland, 27th ed)
Bone softening and weakening usually caused by deficiency or impaired metabolism of vitamin D. Deficiency of calcium, magnesium, or phosphorus may also cause rickets. It predominantly affects children who suffer from severe malnutrition. It manifests with bone pain, fractures, muscle weakness, and skeletal deformities.
A group of infectious diseases that is caused by Rickettsia.
Infections with bacteria of the family RICKETTSIACEAE.
Vaccines for the prevention of diseases caused by various species of Rickettsia.
A viral hemorrhagic fever that is caused by the Rift Valley fever virus, which is transmitted by mosquitoes and infected animals. The infection is typically asymptomatic or causes only mild illness, but can be associated with retinitis.
An anatomic abnormality that occurs during embryonic development, in which the aortic arch is right-sided.
Muscular rigidity which develops in the cadaver usually from 4 to 10 hours after death and lasts 3 or 4 days.
A cyclic amine and alpha-methyl derivative of amantadine with antiviral activity. Although the exact mechanism of action of rimantadine is not understood, this agent appears to exert its antiviral effect against influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the uncoating of the virus and subsequent release of infectious viral nucleic acids into the cytoplasm of infected cells.
A viral disease of cloven-hoofed animals caused by MORBILLIVIRUS. It may be acute, subacute, or chronic with the major lesions characterized by inflammation and ulceration of the entire digestive tract. The disease was declared successfully eradicated worldwide in 2010.
An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, on the basis of epidemiological evidence, is known to be associated with a health-related condition considered important to prevent.
A phenethylamine derivative with tocolytic activity. Ritodrine binds to and activates beta-2 adrenergic receptors of myometrial cells in the uterus, which decreases the intensity and frequency of uterine contractions. Specifically, ritodrine probably activates adenyl cyclase, thereby increasing production of cyclic adenosine monophosphate (cAMP), which in turn enhances the efflux of calcium from vascular smooth muscle cells. A lack of intracellular calcium prevents uterine myometrial contractions. In addition, this agent may directly inactivate myosin light chain kinase, a critical enzyme necessary for the initiation of muscle contractions.
Analogs of RNA cap compounds which do not have a positive charge. These compounds inhibit the initiation of translation of both capped and uncapped messenger RNA.
An anticoccidial agent mainly for poultry.
An acute febrile illness caused by RICKETTSIA RICKETTSII. It is transmitted to humans by bites of infected ticks and occurs only in North and South America. Characteristics include a sudden onset with headache and chills and fever lasting about two to three weeks. A cutaneous rash commonly appears on the extremities and trunk about the fourth day of illness.
Diseases of rodents of the order RODENTIA. This term includes diseases of Sciuridae (squirrels), Geomyidae (gophers), Heteromyidae (pouched mice), Castoridae (beavers), Cricetidae (rats and mice), Muridae (Old World rats and mice), Erethizontidae (porcupines), and Caviidae (guinea pigs).
Antiprotozoal and antimicrobial agent used mainly in veterinary practice.
Resorption in which cementum or dentin is lost from the root of a tooth owing to cementoclastic or osteoclastic activity in conditions such as trauma of occlusion or neoplasms. (Dorland, 27th ed)
A chronic erythematous skin disorder that affects the face. It is characterized by the development of redness in the cheeks, nose, and/or forehead and telangiectasia. Sometimes, the erythematous changes may involve the eyelids.
Infection with any of the rotaviruses. Specific infections include human infantile diarrhea, neonatal calf diarrhea, and epidemic diarrhea of infant mice.
An arsenic derivative which has anticoccidial action and promotes growth in animals.
A viral infection caused by the rubella virus. It is initially manifested with flu-like symptoms that last one or two days, followed by the development of a characteristic red rash which lasts from one to five days. The rash first appears in the neck and face. It subsequently spreads to the rest of the body.
A condition, whose clinical manifestations include intrauterine growth restriction, petechial rash, jaundice, generalized lymphadenopathy, hepatosplenomegaly, peripheral pulmonary stenosis, cataracts, and sensorineural deafness, that is caused by fetal exposure to the rubella virus during the first trimester of pregnancy.
A live attenuated virus vaccine of duck embryo or human diploid cell tissue culture origin, used for routine immunization of children and for immunization of nonpregnant adolescent and adult females of childbearing age who are unimmunized and do not have serum antibodies to rubella. Children are usually immunized with measles-mumps-rubella combination vaccine. (Dorland, 28th ed)
A chromosomal disorder characterized by MENTAL RETARDATION, broad thumbs, webbing of fingers and toes, beaked nose, short upper lip, pouting lower lip, agenesis of corpus callosum, large foramen magnum, keloid formation, pulmonary stenosis, vertebral anomalies, chest wall anomalies, sleep apnea, and megacolon. The disease has an autosomal dominant pattern of inheritance and is associated with deletions of the short arm of chromosome 16 (16p13.3).
Tear or break of an organ, vessel or other soft part of the body, occurring in the absence of external force.
A flavonol glycoside found in many plants, including BUCKWHEAT; TOBACCO; FORSYTHIA; HYDRANGEA; VIOLA, etc. It has been used therapeutically to decrease capillary fragility.
A methylpyrrole-carboxylate from RYANIA that disrupts the RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL to modify CALCIUM release from SARCOPLASMIC RETICULUM resulting in alteration of MUSCLE CONTRACTION. It was previously used in INSECTICIDES. It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM.
A nutritional supplement that is synthesized from adenosine triphosphate (ATP) and the amino acid methionine by the endogenous essential enzyme methionine adenosyltransferase (MAT), with potential antineoplastic activity. Upon administration, S-adenosylmethionine acts as a methyl donor for various transmethylation reactions. In cancer cells, this agent induces the methylation of tumor promoting genes, reverses DNA hypomethylation, and leads to the suppression of oncogene transcription. This induces apoptosis in and inhibits proliferation of susceptible tumor cells.
Flavoring agent and non-nutritive sweetener.
A condition in which there is a derivation of pleasure from inflicting pain, discomfort or humiliation on another person or persons. The sexual significance of sadistic wishes or behavior may be conscious or unconscious.
An extremely rare type of short rib polydactyly syndrome with neonatal onset. The disease has characteristics of polydactyly, hydropic appearance, and small thorax with short horizontal ribs causing fatal cardiorespiratory distress. Affected patients also have extreme micromelia ('flipper-like' extremities), pointed metaphyses and a range of other ossification defects. Extraskeletal manifestations may include polycystic kidneys, transposition of the great vessels and atresia of the gastrointestinal and genitourinary systems.
The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.
A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907)
A beta hydroxy acid that occurs as a natural compound in plants. It has direct activity as an anti-inflammatory agent and acts as a topical antibacterial agent due to its ability to promote exfoliation.
Any solution of sodium chloride (NaCl) in water with a concentration of NaCl higher than that found in physiological saline (0.9% w/v). When administered in vivo, hypertonic saline (HTS) exhibits several physiological effects beneficial to cerebral injury including: 1) osmotic and vasoregulatory - by promoting the flow of excess water from cerebral tissue to the blood via osmosis and decreasing edema in the vascular endothelium of injured tissues, thus lowering vascular resistance and allowing more blood flow; 2) hemodynamic - by effectively expanding plasma volume; 3) immunomodulatory - by preventing leukocytes from becoming activated and adhering to injured neurons and; 4) neurochemical - by counteracting detrimental excitatory amino acids through the normalization of neuronal cell membranes and by restoration of normal electrolyte and neurotransmitter levels in brain cells, and normal cell volumes.
A solution used for irrigating the mouth in xerostomia and as a substitute for saliva.
Presence of small calculi in the terminal salivary ducts (salivary sand), or stones (larger calculi) found in the larger ducts.
Calculi occurring in a salivary gland. Most salivary gland calculi occur in the submandibular gland, but can also occur in the parotid gland and in the sublingual and minor salivary glands.
A non-neoplastic or neoplastic (benign or malignant) disorder involving a salivary gland.
A fistula between a salivary duct or gland and the cutaneous surface of the oral cavity.
A benign or malignant neoplasm that affects the major or minor salivary glands. Representative examples of benign neoplasms include Warthin tumor, monomorphic adenoma, and pleomorphic adenoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma.
Infections with bacteria of the genus SALMONELLA.
Infections in animals with bacteria of the genus SALMONELLA.
Acute or chronic inflammation of the fallopian tube. It is most often caused by Neisseria gonorrhoeae and Chlamydia trachomatis infections. The infections usually originate in the vagina and ascend to the fallopian tube. Symptoms include abdominal, pelvic, and lower back pain, pain during ovulation and sexual intercourse, fever, nausea, and vomiting. Complications include infertility and ectopic pregnancy.
Tetrahydroisoquinolinol alkaloids in both dextro and levo forms, originally found in SALSOLA plants.
An element of the rare earth family of metals. It has the atomic symbol Sm, atomic number 62, and atomic weight 150.36. The oxide is used in the control rods of some nuclear reactors.
Sandhoff disease is a progressive neurodegenerative disorder characterized by an accumulation of GM2 gangliosides, particularly in neurons, and is clinically indistinguishable from Tay-Sachs disease (272800).
Anthelmintic isolated from the dried unexpanded flower heads of Artemisia maritima and other species of Artemisia found principally in Russian and Chinese Turkestan and the Southern Ural region. (From Merck, 11th ed.)
An octapeptide analog of angiotensin II (bovine) with amino acids 1 and 8 replaced with sarcosine and alanine, respectively. It is a highly specific competitive inhibitor of angiotensin II that is used in the diagnosis of HYPERTENSION.
An idiopathic inflammatory disorder characterized by the formation of non-necrotizing epithelioid granulomas which contain giant cells. It usually affects the lungs, lymph nodes, liver, and skin. Cardiac involvement is also possible.
Formation of non-necrotizing granulomas in the skin. It may be a manifestation of systemic sarcoidosis or may also arise in isolation.
Sarcoidosis affecting predominantly the lungs, the site most frequently involved and most commonly causing morbidity and mortality in sarcoidosis. Pulmonary sarcoidosis is characterized by sharply circumscribed granulomas in the alveolar, bronchial, and vascular walls, composed of tightly packed cells derived from the mononuclear phagocyte system. The clinical symptoms when present are dyspnea upon exertion, nonproductive cough, and wheezing. (Cecil Textbook of Medicine, 19th ed, p431)
Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA.
A systemic disease which can present with cutaneous lesions with or without internal involvement. Tumors are caused by Human herpesvirus 8 (HHV8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV).
A rare entity characterized by localized but destructive growth of a tumor consisting of highly atypical, immature mast cells.(WHO, 2001)
Infection of the striated muscle of mammals by parasites of the genus SARCOCYSTIS. Disease symptoms such as vomiting, diarrhea, muscle weakness, and paralysis are produced by sarcocystin, a toxin produced by the organism.
A contagious cutaneous inflammation caused by the bite of the mite SARCOPTES SCABIEI. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body.
A streptococcal infection, mainly occurring among children, that is characterized by a red skin rash, sore throat, and fever.
Scheuermann disease is characterized by lumbar or thoracic kyphosis or both, back pain, and a variety of vertebral changes including wedging, endplate irregularity, narrowing of disc spaces, Schmorl nodes, and detached epiphyseal rings. It is reported to occur more frequently in boys than in girls (summary by McKenzie and Sillence, 1992).
A parasitic infection caused by flukes of the genus Schistosoma. Signs and symptoms include fever, abdominal pain, eosinophilia and hepatosplenomegaly. If left untreated it may eventually cause liver damage leading to cirrhosis, bladder cancer and kidney failure.
An infection that is caused by Schistosoma japonicum.
An infection that is caused by Schistosoma mansoni.
Agents that act systemically to kill adult schistosomes.
A disorder in which the individual suffers from both symptoms that qualify as schizophrenia and symptoms that qualify as a mood disorder (e.g., depression or bipolar disorder) for a substantial portion (but not all) of the active period of the illness; for the remainder of the active period of the illness, the individual suffers from delusions or hallucinations in the absence of prominent mood symptoms.
A disorder characterized by an enduring pattern of extreme social detachment and lack of involvement in interpersonal activities, coupled with emotional coldness.
Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target.
A subtype of schizophrenia characterized by a psychomotor disturbance that may involve motoric immobility, excessive motor activity, extreme negativism or mutism, peculiarities of voluntary movement, echolalia, and/or echopraxia.
An obsolete concept, historically used for childhood mental disorders thought to be a form of schizophrenia. It was in earlier versions of DSM but is now included within the broad concept of PERVASIVE DEVELOPMENT DISORDERS.
A subtype of schizophrenia characterized by disorganized speech, disorganized behavior, and a flat or inappropriate affect; associated features include grimacing, mannerisms, and other oddities of behavior. Criteria for the catatonic type of schizophrenia are not met.
A chronic form of schizophrenia characterized primarily by the presence of persecutory or grandiose delusions, often associated with hallucination.
A subtype of schizophrenia in which the individual has suffered an episode of schizophrenia but there are no longer any delusions, hallucinations, disorganized speech or behavior. Residual symptoms are seen in the form of negative symptoms (such as flat affect or avolition) or attenuated positive symptoms (such as odd beliefs).
The artificial language of schizophrenic patients - neologisms (words of the patient's own making with new meanings).
A disorder that differs from schizophrenia specifically in total duration (schizophreniform disorder lasts at least 1 month but less than 6 months whereas schizophrenia lasts at least 6 months); schizophreniform disorder also typically causes less impairment in the individual's social and occupational functioning.
A soluble beta-D-glucan produced by the Basidiomycetes fungus, Schizophyllum commune Fries, with potential immunomodulating and antitumor activities. Although sizofiran's exact mechanism of action has yet to be fully elucidated, this agent appears to stimulate the immune system by increasing cytokine production, activating macrophages and enhancing the activity of polymorphonuclear leukocytes (PML) and natural killer (NK) cells.
A disorder characterized by an enduring pattern of inability to establish close relationships coupled with cognitive or perceptual distortions, odd beliefs and speech, and eccentric behavior and appearance.
A classification for rare genetic syndromes with an autosomal recessive pattern of inheritance. Clinical features include muscle stiffness and weakness, facial and skeletal abnormalities with joint contractures and short stature. Two types have been characterized: Schwartz-Jampel Syndrome type I (SJSI) and Schwartz-Jampel Syndrome type II (SJSII). SJSI is associated with a mutation of the HSPG2 gene on chromosome 1 and has been further characterized into two subtypes IA and IB. SJSIA is more common, less severe in presentation and is seen later in childhood than SJSIB. For both SJSI subtypes, prognosis is favorable as the main feature of muscle stiffness is slowly progressive, if at all, and is compatible with a normal life span. SJSII is apparent at birth, shares the same clinical profile and mutation in the LIFR gene noted in Stuve-Wiedemann Syndrome and is thus presumed to be the same disorder. In contrast to SJSI, its presentation is more severe and likelihood of survivability is much lower.
A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of SCIATIC NEUROPATHY; RADICULOPATHY (involving the SPINAL NERVE ROOTS; L4, L5, S1, or S2, often associated with INTERVERTEBRAL DISK DISPLACEMENT); or lesions of the CAUDA EQUINA.
A developmental defect characterized by abnormal connection of or more pulmonary veins to the superior or inferior vena cava, the right atrium, or the coronary sinus, resulting in a left-to-right shunt of oxygenated blood.
A disorder affecting the sclera. Examples include inflammatory processes (e.g., scleritis and episcleritis), and degenerative processes. Primary tumors of the sclera are extremely rare.
Hard non pitting edema and induration of the skin; a finding associated with Buschke's disease.
A diffuse hardening of skin and subcutaneous adipose tissue, associated with minimal inflammation without fat necrosis, that typically affects critically ill preterm neonates during the first week of life.
A chronic disorder, possibly autoimmune, marked by excessive production of collagen which results in hardening and thickening of body tissues. Localized scleroderma typically affects the skin, with formation of patches or lines of thick and unyielding tissue; there can be muscle and underlying tissue involvement as well as occasional joint complications. The affected areas of skin can be restrictive and disfiguring. The shape, depth and location of the affected area is used to classify one of the four types of local scleroderma. An individual can have a combination of localized scleroderma types.
A chronic disorder, possibly autoimmune, marked by excessive production of collagen which results in hardening and thickening of body tissues. The two types of systemic scleroderma, limited cutaneous and diffuse cutaneous are classified with focus on the extent of affected skin. A relationship exists between the extent of skin area affected and degree of internal organ/system involvement. Systemic scleroderma can manifest itself in pulmonary fibrosis, Raynaud's syndrome, digestive system telangiectasias, renal hypertension and/or pulmonary hypertension.
Chemical agents injected into blood vessels and lymphatic sinuses to shrink or cause localized THROMBOSIS; FIBROSIS, and obliteration of the vessels. This treatment is applied in a number of conditions such as VARICOSE VEINS; HEMORRHOIDS; GASTRIC VARICES; ESOPHAGEAL VARICES; PEPTIC ULCER HEMORRHAGE.
A pathological hardening or thickening of tissue, especially that of the interstitial substance.
A congenital or acquired spinal deformity characterized by lateral curvature of the spine.
A tropane alkaloid derived from plants of the nightshade family (Solanaceae), specifically Hyoscyamus niger and Atropa belladonna, with anticholinergic, antiemetic and antivertigo properties. Structurally similar to acetylcholine, scopolamine antagonizes acetylcholine activity mediated by muscarinic receptors located on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. The agent is used to cause mydriasis, cycloplegia, to control the secretion of saliva and gastric acid, to slow gut motility, and prevent vomiting.
The hydrobromide salt form of scopolamine, a tropane alkaloid derived from plants of the nightshade family (Solanaceae), specifically Hyoscyamus niger and Atropa belladonna, with anticholinergic, antiemetic and antivertigo properties. Structurally similar to acetylcholine, scopolamine antagonizes acetylcholine activity mediated by muscarinic receptors located on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. The agent is used to cause mydriasis, cycloplegia, to control the secretion of saliva and gastric acid, to slow gut motility, and prevent vomiting.
A localized defect in the visual field bordered by an area of normal vision. This occurs with a variety of EYE DISEASES (e.g., RETINAL DISEASES and GLAUCOMA); OPTIC NERVE DISEASES, and other conditions.
A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called PRIONS.
Infection with larvae of the blow fly Cochliomyia hominivorax (Callitroga americanum), a common cause of disease in livestock in the southern and southwestern U.S.A.
An acute infectious disease caused by ORIENTIA TSUTSUGAMUSHI. It is limited to eastern and southeastern Asia, India, northern Australia, and the adjacent islands. Characteristics include the formation of a primary cutaneous lesion at the site of the bite of an infected mite, fever lasting about two weeks, and a maculopapular rash.
Abnormally low concentrations of vitamin C in the blood.
A sensation of discomfort associated with travel over water, which may include nausea, vomiting, dizziness, or sweating.
Diseases of the sebaceous glands such as sebaceous hyperplasia and sebaceous cell carcinoma (SEBACEOUS GLAND NEOPLASMS).
A benign or malignant neoplasm that arises from the sebaceous glands. Representative examples include sebaceous adenoma and sebaceous carcinoma.
A chronic inflammatory disease of the skin with unknown etiology. It is characterized by moderate ERYTHEMA, dry, moist, or greasy (SEBACEOUS GLAND) scaling and yellow crusted patches on various areas, especially the scalp, that exfoliate as dandruff. Seborrheic dermatitis is common in children and adolescents with HIV INFECTIONS.
A barbiturate that is used as a sedative. Secobarbital is reported to have no anti-anxiety activity.
A non-proteinaceous signaling molecule that is generated by intracellular enzymes that respond to the binding of extracellular ligands to cell surface receptors. These compounds serve as intermediate signals for a diverse set of cellular processes.
A peptide hormone of about 27 amino acids from the duodenal mucosa that activates pancreatic secretion and lowers the blood sugar level. (USAN and the USP Dictionary of Drug Names, 1994, p597)
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or ""seizure disorder.""
A selective, irreversible inhibitor of Type B monoamine oxidase that is used for the treatment of newly diagnosed patients with PARKINSON DISEASE, and for the treatment of depressive disorders. The compound without isomeric designation is Deprenyl.
A nonmetallic chemical element found in trace amounts in human body. Selenium primarily occurs in vivo as selenocompounds, mostly selenoproteins such as glutathione peroxidase and thioredoxin reductase (enzymes responsible for detoxification). Alone or in combination with Vitamin E, selenocompounds act as antioxidants. These agents scavenge free radicals; prevent blood clots by inhibiting platelet aggregation; strengthen the immune system; and have been shown, in some instances, to inhibit chromosomal damage and mutations. Exhibiting chemopreventive activity, selenocompounds also inhibit the induction of protein kinase C.
A selenium (Se) analogue of methionine in which sulfur is replaced with the trace element selenium. Selenomethionine (SeMet) can incorporate into proteins in place of methionine with no effects on protein structure and function, providing a mechanism for reversible Se storage in organs and tissues. Free selenium is incorporated into selenocysteine, an amino acid found in more than thirty selenoproteins including the glutathione peroxidases (GPx) enzymes, thioredoxin reductase (TR) and the iodothyronine deiodinase enzymes.
A malignant germ cell tumor arising from the testis. It is believed that it is derived from the sexually undifferentiated embryonic gonad. Treatment with radiotherapy is highly successful when the tumor is diagnosed in localized stages, which represents the majority of presentations of seminoma.
4-Methyl derivative of LOMUSTINE; (CCNU). An antineoplastic agent which functions as an alkylating agent.
Benign, pigmented spots on the skin that are associated with aging and exposure to ultraviolet radiation from the sun. The spots are found on areas of the body that are most often exposed to the sun; including the hands, face, shoulders, arms, forehead, and scalp. In some cases, this condition may mimic melanoma.
An extract made from the dried leaflets on the pods of Cassia angustifolia or Cassia acutifolia with cathartic activity. Dimeric glycosides in dried senna extract are converted to the active monoanthrones by bacterial action in the colon. Through direct effects on enterocytes, enteric neurons, and muscle, monoanthrones produce giant migrating colonic contractions in addition to water and electrolyte secretion. As do other stimulant laxatives, monoanthrones may induce a limited low-grade inflammation in the colon through activation of prostaglandin/cyclic AMP and nitric oxide/cyclic GMP pathways and perhaps inhibition of Na+, K+-ATPase.
Disorders of the special senses (i.e., VISION; HEARING; TASTE; and SMELL) or somatosensory system (i.e., afferent components of the PERIPHERAL NERVOUS SYSTEM).
The absence or restriction of the usual external sensory stimuli to which the individual responds.
Inflammation of the throat due to Streptococcus pyogenes.
Systemic disease associated with the presence of pathogenic microorganisms or their toxins in the blood.
A non-essential amino acid in humans (synthesized by the body), Serine is present and functionally important in many proteins. With an alcohol group, serine is needed for the metabolism of fats, fatty acids, and cell membranes; muscle growth; and a healthy immune system. It also plays a major role in pyrimidine, purine, creatine, and porphyrin biosynthetic pathways. Serine is also found at the active site of the serine protease enzyme class that includes trypsin and chymotrypsin. (NCI04)
A protein that plays a role in the inhibition of serine proteinases.
Any agent that binds to and blocks serotonin receptors.
A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES.
A sex cord-stromal tumor of the testis or the ovary. It is characterized by the presence of Sertoli cells forming tubules. Leydig cells are rare or absent. It may be associated with Peutz-Jeghers syndrome. In males, the presenting symptom is a slow growing testicular mass. Most cases follow a benign clinical course. In females it may present with estrogenic or androgenic manifestations. The vast majority of cases have a benign clinical course.
Delayed-type hypersensitivity reaction to foreign proteins derived from an animal serum. It occurs approximately six to twenty one days following the administration of the foreign antigen. Symptoms include fever, arthralgias, myalgias, skin eruptions, lymphadenopathy, chest pain, and dyspnea. Certain drugs (e.g., antibiotics, anticancer agents, and anti-inflammatory medications) and infectious disorders (e.g., hepatitis B) may also cause serum sickness-like reaction.
The edible oil extracted from the seeds of Sesamum indicum. Sesame oil is used as a cooking oil and as a food ingredient. It is also used as an ingredient in medicinal preparations.
Infection with nematodes of the genus Setaria. This condition is usually seen in cattle and equines and is of little pathogenic significance, although migration of the worm to the eye may lead to blindness.
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
A carbamate insecticide and parasiticide. It is a potent anticholinesterase agent belonging to the carbamate group of reversible cholinesterase inhibitors. It has a particularly low toxicity from dermal absorption and is used for control of head lice in some countries.
Abnormal number or structure of the SEX CHROMOSOMES. Some sex chromosome aberrations are associated with SEX CHROMOSOME DISORDERS and SEX CHROMOSOME DISORDERS OF SEX DEVELOPMENT.
In gonochoristic organisms, congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. Effects from exposure to abnormal levels of GONADAL HORMONES in the maternal environment, or disruption of the function of those hormones by ENDOCRINE DISRUPTORS are included.
A class of steroid hormones that specifically binds to and activates androgen, progesterone or estrogen receptors. Sex steroids activate various signaling pathways involved in the development and maintenance of secondary sexual characteristics, reproductive processes, blood salt balance, response to stress, neuronal function and a number of metabolic processes.
Any violation of established legal or moral codes in respect to sexual behavior.
A disorder characterized by recurrent or persistent extreme aversion to, and avoidance of, all genital contact with a sexual partner. The aversion to sexual contact is not attributable to another psychiatric disorder.
A disorder characterized by recurrent sexual urges, fantasies, or behaviors involving the act (real, not simulated) of being humiliated, beaten, bound, or otherwise made to suffer.
A disorder characterized by recurrent sexual urges, fantasies, or behaviors involving acts (real, not simulated) in which the psychological or physical suffering of a victim is sexually exciting to the individual.
A disorder acquired through sexual contact.
Bacterial diseases transmitted or propagated by sexual conduct.
Viral diseases which are transmitted or propagated by sexual conduct.
Sézary syndrome is an aggressive form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions. In Sézary syndrome, the cancerous T cells, called Sézary cells, are present in the blood, skin, and lymph nodes. A characteristic of Sézary cells is an abnormally shaped nucleus, described as cerebriform.People with Sézary syndrome develop a red, severely itchy rash (erythroderma) that covers large portions of their body. Sézary cells are found in the rash. However, the skin cells themselves are not cancerous; the skin problems result when Sézary cells move from the blood into the skin. People with Sézary syndrome also have enlarged lymph nodes (lymphadenopathy). Other common signs and symptoms of this condition include hair loss (alopecia), skin swelling (edema), thickened skin on the palms of the hands and soles of the feet (palmoplantar keratoderma), abnormalities of the fingernails and toenails, and lower eyelids that turn outward (ectropion). Some people with Sézary syndrome are less able to control their body temperature than people without the condition.The cancerous T cells can spread to other organs in the body, including the lymph nodes, liver, spleen, and bone marrow. In addition, affected individuals have an increased risk of developing another lymphoma or other type of cancer.Sézary syndrome most often occurs in adults over age 60 and usually progresses rapidly; historically, affected individuals survived an average of 2 to 4 years after development of the condition, although survival has improved with newer treatments.Although Sézary syndrome is sometimes referred to as a variant of another cutaneous T-cell lymphoma called mycosis fungoides, these two cancers are generally considered separate conditions.
A condition in which closely related persons, usually in the same family, share the same delusions.
Diseases of domestic and mountain sheep of the genus Ovis.
Bovine respiratory disease found in animals that have been shipped or exposed to CATTLE recently transported. The major agent responsible for the disease is MANNHEIMIA HAEMOLYTICA and less commonly, PASTEURELLA MULTOCIDA or HAEMOPHILUS SOMNUS. All three agents are normal inhabitants of the bovine nasal pharyngeal mucosa but not the LUNG. They are considered opportunistic pathogens following STRESS, PHYSIOLOGICAL and/or a viral infection. The resulting bacterial fibrinous BRONCHOPNEUMONIA is often fatal.
Involuntary contraction or twitching of the muscles.
A life-threatening condition that requires immediate medical intervention. It is characterized by reduced blood flow that may result in damage of multiple organs. Types of shock include cardiogenic, hemorrhagic, septic, anaphylactic, and traumatic shock.
Severely decreased cardiac output with evidence of inadequate end-organ perfusion (i.e., tissue hypoxia) in the presence of adequate intravascular volume.
Acute hemorrhage or excessive fluid loss resulting in HYPOVOLEMIA.
A state of acute circulatory failure characterized by persistent arterial hypotension despite adequate fluid resuscitation or by tissue hypoperfusion unexplained by other causes.
Hypoperfusion of body tissues occurring during or after a surgical procedure, and resulting in cellular injury and vital organ dysfunction.
An intestinal failure due to either a congenital defect, intestinal infarction or extensive surgical resection of the intestinal tract that results in a functional small intestine of less than 200cm in length and is characterised by diarrhoea, nutrient malabsorption, bowel dilation and dysmobility.
A rare congenital lethal syndrome characterized by the presence of extra fingers and toes and short ribs, the latter resulting in inability of the lungs to expand. The newborn dies shortly after birth.
A sensation of discomfort emanating from the muscles, tendons, joints (acromioclavicular or glenohumeral), or supporting structures between the neck and upper arm.
3-beta-D-Ribofuranosylmaleimide. Antineoplastic antibiotic isolated from Streptomyces showdoensis. It is possibly active also as a sulfhydryl reagent.
Hemorrhagic necrosis that was first demonstrated in rabbits with a two-step reaction, an initial local (intradermal) or general (intravenous) injection of a priming endotoxin (ENDOTOXINS) followed by a second intravenous endotoxin injection (provoking agent) 24 h later. The acute inflammation damages the small blood vessels. The following intravascular coagulation leads to capillary and venous THROMBOSIS and NECROSIS. Shwartzman phenomenon can also occur in other species with a single injection of a provoking agent, and during infections or pregnancy. Its susceptibility depends on the status of IMMUNE SYSTEM, coagulation, FIBRINOLYSIS, and blood flow.
A progressive neurodegenerative condition of the central and autonomic nervous systems characterized by atrophy of the preganglionic lateral horn neurons of the thoracic spinal cord. This disease is generally considered a clinical variant of MULTIPLE SYSTEM ATROPHY. Affected individuals present in the fifth or sixth decade with ORTHOSTASIS and bladder dysfunction; and later develop FECAL INCONTINENCE; anhidrosis; ATAXIA; IMPOTENCE; and alterations of tone suggestive of basal ganglia dysfunction. (From Adams et al., Principles of Neurology, 6th ed, p536)
An acute or chronic inflammatory process affecting a salivary gland. Signs and symptoms include pain and tenderness in the affected area.
A benign, inflammatory, variably ulcerated, occasionally bilateral, self-healing lesion of the minor salivary glands that is often confused clinically and histologically with carcinoma.
A group of symptoms that are two- to three-fold more common in those who work in large, energy-efficient buildings, associated with an increased frequency of headaches, lethargy, and dry skin. Clinical manifestations include hypersensitivity pneumonitis (ALVEOLITIS, EXTRINSIC ALLERGIC); allergic rhinitis (RHINITIS, ALLERGIC, PERENNIAL); ASTHMA; infections, skin eruptions, and mucous membrane irritation syndromes. Current usage tends to be less restrictive with regard to the type of building and delineation of complaints. (From Segen, Dictionary of Modern Medicine, 1992)
A condition caused by dysfunctions related to the SINOATRIAL NODE including impulse generation (CARDIAC SINUS ARREST) and impulse conduction (SINOATRIAL EXIT BLOCK). It is characterized by persistent BRADYCARDIA, chronic ATRIAL FIBRILLATION, and failure to resume sinus rhythm following CARDIOVERSION. This syndrome can be congenital or acquired, particularly after surgical correction for heart defects.
An individual who is heterozygous for the mutation that causes sickle cell anemia.
A form of pneumoconiosis resulting from inhalation of iron in the mining dust or welding fumes.
Pathological processes in the SIGMOID COLON region of the large intestine (INTESTINE, LARGE).
Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient.
Digestive system manifestations of diseases of the gastrointestinal system or of other organs.
Respiratory system manifestations of diseases of the respiratory tract or of other organs.
A hydrated form of silicon dioxide. It is commonly used in the manufacture of TOOTHPASTES and as a stationary phase for CHROMATOGRAPHY.
A form of pneumoconiosis resulting from inhalation of dust containing crystalline form of SILICON DIOXIDE, usually in the form of quartz. Amorphous silica is relatively nontoxic.
Pulmonary or extrapulmonary infection caused by MYCOBACTERIUM TUBERCULOSIS or nontuberculous mycobacteria in a patient with silicosis.
A form of alveolitis or PNEUMONITIS caused by hypersensitivity to high level of inhaled nitrogen oxides, decomposition products of silage.
A silver salt with powerful germicidal activity. It has been used topically to prevent OPHTHALMIA NEONATORUM.
A sulfonamide-based topical agent with antibacterial and antifungal activity. Silver sulfadiazine may act through a combination of the activity of silver and sulfadiazine. When this agent interacts with sodium chloride-containing body fluids, silver ions are released slowly and sustainably into wounded areas. Ionized silver atoms catalyze the formation of disulfide bonds leading to protein structural changes and inactivating thiol-containing enzymes; silver ions may also intercalate DNA thereby interfering with replication and transcription of bacteria. As a competitive inhibitor of para-aminobenzoic acid (PABA), sulfadiazine inhibits bacterial dihydropteroate synthase, thereby resulting in disruption of folic acid metabolism and ultimately DNA synthesis.
A mixture of flavonolignans isolated from the milk thistle plant Silybum marianum. Silymarin may act as an antioxidant, protecting hepatic cells from chemotherapy-related free radical damage. This agent may also promote the growth of new hepatic cells. (NCI04)
A mixture of polydimethylsiloxanes with antifoaming and anti-bloating effects. Simethicone reduces the surface tension of gas bubbles causing them to coalesce into larger bubbles that can be passed more easily by belching or flatulence.
A synthetic C-terminal octapeptide identical to the sequences of the endogenous cholecystokinin hormone. Mimic action of cholecystokinin, sincalide induces gallbladder smooth muscle contraction directly, thereby reducing gallbladder size, inducing bile evacuation, and secretion of pancreatic enzymes. In addition, this agent decreases esophageal sphincter tone and delays gastric emptying via cholinergic signaling.
Disturbance in the atrial activation that is caused by transient failure of impulse conduction from the SINOATRIAL NODE to the HEART ATRIA. It is characterized by a delayed in heartbeat and pauses between P waves in an ELECTROCARDIOGRAM.
Formation or presence of a blood clot (THROMBUS) in the CRANIAL SINUSES, large endothelium-lined venous channels situated within the SKULL. Intracranial sinuses, also called cranial venous sinuses, include the superior sagittal, cavernous, lateral, petrous sinuses, and many others. Cranial sinus thrombosis can lead to severe HEADACHE; SEIZURE; and other neurological defects.
An acute or chronic inflammatory process affecting the mucous membranes of any sinus cavity.
A developmental defect in which the legs are fused together.
The sulfate salt form of sisomicin, a broad-spectrum aminoglycoside antibiotic isolated from Micromonospora inyoensis. Sisomicin is strucurally similar to gentamicin but has a unique unsaturated diamino sugar. Of the aminoglycoside antibiotics, sisomicin has the greatest activity against gram-positive bacteria.
A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and gamma-isomers have been characterized.
A non-penetrating amino reagent (commonly called SITS) which acts as an inhibitor of anion transport in erythrocytes and other cells.
A congenital abnormality in which organs in the THORAX and the ABDOMEN are opposite to their normal positions (situs solitus) due to lateral transposition. Normally the STOMACH and SPLEEN are on the left, LIVER on the right, the three-lobed right lung is on the right, and the two-lobed left lung on the left. Situs inversus has a familial pattern and has been associated with a number of genes related to microtubule-associated proteins.
Sjogren-Larsson syndrome is an autosomal recessive, early childhood-onset disorder characterized by ichthyosis, mental retardation, spastic paraparesis, macular dystrophy, and leukoencephalopathy. It is caused by deficiency of fatty aldehyde dehydrogenase (summary by Lossos et al., 2006).
A skin abnormality that is present at birth or detected in the neonatal period.
A disorder involving lesions or eruptions of the skin, usually without inflammation.
Skin diseases characterized by local or general distributions of blisters. They are classified according to the site and mode of blister formation. Lesions can appear spontaneously or be precipitated by infection, trauma, or sunlight. Etiologies include immunologic and genetic factors. (From Scientific American Medicine, 1990)
Diseases of the skin with a genetic component, usually the result of various inborn errors of metabolism.
An inflammatory process affecting the skin, caused by bacteria, viruses, parasites, or fungi. Examples of bacterial infection include carbuncles, furuncles, impetigo, erysipelas, and abscesses. Examples of viral infection include shingles, warts, molluscum contagiosum, and pityriasis rosea. Examples of parasitic infection include scabies and lice. Examples of fungal infection include athlete's foot, yeast infection, and ringworm.
Diseases of the skin associated with underlying metabolic disorders.
Skin diseases caused by ARTHROPODS; HELMINTHS; or other parasites.
Dermatologic disorders attendant upon non-dermatologic disease or injury.
A benign or malignant tumor involving the skin. Representative examples of benign skin neoplasms include the benign melanocytic skin nevus, acanthoma, sebaceous adenoma, sweat gland adenoma, lipoma, hemangioma, fibroma, and benign fibrous histiocytoma. Representative examples of malignant skin neoplasms include basal cell carcinoma, squamous cell carcinoma, melanoma, and Kaposi sarcoma.
A polypoid lesion composed of fibrous tissue and epithelium. Representative examples include skin tag, anal fibroepithelial polyp, and gingival fibroepithelial polyp.
A circumscribed and often suppurating skin crater which usually includes loss of skin integrity of the superficial skin or the mucous membranes.
The presence of an increased degree of wrinkling (irregular folds and indentations) of the skin as compared with age-related norms.
A benign or malignant neoplasm that affects the bones and structures of the skull.
An intermittent cessation of airflow at the mouth and nose during sleep. Apneas of at least 10 seconds are considered important, but persons with sleep apnea may have apneas of 20 seconds to up to 2 or 3 minutes. Patients may have up to 15 events per hour of sleep.
The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder.
An abnormality of sleep including such phenomena as 1) insomnia/hypersomnia, 2) non-restorative sleep, 3) sleep schedule disorder, 4) excessive daytime somnolence, 5) sleep apnea, and 6) restlessness.
A disorder characterized by incomplete arousals from sleep associated with behavior suggesting extreme fright. This condition primarily affects children and young adults and the individual generally has no recall of the event. Episodes tend to occur during stage III or IV. SOMNAMBULISM is frequently associated with this condition. (Adams et al., Principles of Neurology, 6th ed, p391)
Diseases of viral origin, characterized by incubation periods of months to years, insidious onset of clinical manifestations, and protracted clinical course. Though the disease process is protracted, viral multiplication may not be unusually slow. Conventional viruses produce slow virus diseases such as SUBACUTE SCLEROSING PANENCEPHALITIS, progressive multifocal leukoencephalopathy (LEUKOENCEPHALOPATHY, PROGRESSIVE MULTIFOCAL), and AIDS. Diseases produced by unconventional agents were originally considered part of this group. They are now called PRION DISEASES.
A condition that is caused by infection with Variola, and that is characterized by small, raised bumps.
A live VACCINIA VIRUS vaccine of calf lymph or chick embryo origin, used for immunization against smallpox. It is now recommended only for laboratory workers exposed to smallpox virus. Certain countries continue to vaccinate those in the military service. Complications that result from smallpox vaccination include vaccinia, secondary bacterial infections, and encephalomyelitis. (Dorland, 28th ed)
Smallpox that occurs in an individual who has been vaccinated.
A sudden violent, spasmodic, audible expiration of breath through the nose and mouth.
Outcomes that describe an individual's relationships with others
Situations affecting a significant number of people, that are believed to be sources of difficulty or threaten the stability of the community, and that require programs of amelioration.
A cellulose derivative which is a beta-(1,4)-D-glucopyranose polymer. It is used as a bulk laxative and as an emulsifier and thickener in cosmetics and pharmaceuticals and as a stabilizer for reagents.
A metal halide composed of sodium and chloride with sodium and chloride replacement capabilities. When depleted in the body, sodium must be replaced in order to maintain intracellular osmolarity, nerve conduction, muscle contraction and normal renal function.
The sodium salt of dichloroacetic acid with potential antineoplastic activity. Dichloroacetate ion inhibits pyruvate dehydrogenase kinase, resulting in the inhibition of glycolysis and a decrease in lactate production. This agent may stimulate apoptosis in cancer cells by restoring normal mitochondrial-induced apoptotic signaling.
An anionic surfactant, usually a mixture of sodium alkyl sulfates, mainly the lauryl; lowers surface tension of aqueous solutions; used as fat emulsifier, wetting agent, detergent in cosmetics, pharmaceuticals and toothpastes; also as research tool in protein biochemistry.
A synthetic therapeutic diphosphonate analogue of endogenous pyrophosphate. As a member of the family of drugs known as bisphosphonates, etidronate disodium differs from endogenous pyrophosphate in its resistance to enzymatic hydrolysis. This agent adsorbs to hydroxyapatite cells and reduces the number of osteoclasts, thereby inhibiting abnormal bone resorption. Etidronate may also directly stimulate bone formation by osteoblasts. (NCI04)
One of the FLAVORING AGENTS used to impart a meat-like flavor.
A sodium salt of gold thiosulfate. It has uses like the ORGANOGOLD COMPOUNDS.
The sodium salt form of heparin. As a glycosaminoglycan anticoagulant, heparin sodium binds to antithrombin III to form a heparin-antithrombin III complex. The complex binds to and irreversibly inactivates thrombin and other activated clotting factors IX, X, XI, and XII and prevents the transformation of fibrinogen to fibrin. (NCI)
A chlorine compound often used as a disinfectant or a bleaching agent. Sodium hypochlorite in 0.5% w/v solution is called Dakin's solution, and is used as an antiseptic to clean infected topical wounds.
A compound forming white, odorless deliquescent crystals and used as iodine supplement, expectorant or in its radioactive (I-131) form as an diagnostic aid, particularly for thyroid function tests.
The sodium salts of the fatty acids in cod liver oil; an irritant and sclerosing agent used to treat varicose veins and arthritic joints.
Nitrous acid sodium salt. Used in many industrial processes, in meat curing, coloring, and preserving, and as a reagent in ANALYTICAL CHEMISTRY TECHNIQUES. It is used therapeutically as an antidote in cyanide poisoning. The compound is toxic and mutagenic and will react in vivo with secondary or tertiary amines thereby producing highly carcinogenic nitrosamines.
The sodium salt of 4-hydroxybutyric acid. It is used for both induction and maintenance of ANESTHESIA.
The phosphate sodium salt form of riboflavin, a water-soluble and essential micronutrient that is the principal growth-promoting factor in naturally occurring vitamin B complexes. Riboflavin phosphate sodium is converted to 2 coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are necessary for energy production by aiding in the metabolism of fats, carbohydrates and proteins and are required for red blood cell formation and respiration, antibody production and for regulating human growth and reproduction. Riboflavin phosphate sodium is essential for healthy skin, nails and hair growth.
A non-steroidal anti-inflammatory agent that is less effective than equal doses of ASPIRIN in relieving pain and reducing fever. However, individuals who are hypersensitive to ASPIRIN may tolerate sodium salicylate. In general, this salicylate produces the same adverse reactions as ASPIRIN, but there is less occult gastrointestinal bleeding. (From AMA Drug Evaluations Annual, 1992, p120)
An anionic surface-active agent used for its wetting properties in industry and used in medicine as an irritant and sclerosing agent for hemorrhoids and varicose veins.
The sodium salt form of valproic acid with anti-epileptic activity. Valproate sodium is converted into its active form, valproate ion, in blood. Although the mechanism of action remains to be elucidated, valproate sodium increases concentrations of gamma-aminobutyric acid (GABA) in the brain, probably due to inhibition of the enzymes responsible for the catabolism of GABA. This potentiates the synaptic actions of GABA. Valproate sodium may also affect potassium channels, thereby creating a direct membrane-stabilizing effect.
A benign, intermediate, or malignant neoplasm that arises from the soft tissue. The most common types are lipomatous (fatty), vascular, smooth muscle, fibrous, and fibrohistiocytic neoplasms.
A mixture of alpha-chaconine and alpha-solanine, found in SOLANACEAE plants.
A single, fluid-filled cyst in the breast parenchyma.
A category of psychiatric disorders which are characterized by the presence of physical symptoms that suggest a medical condition but are not fully explained by any known medical reasons.
A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.
A rare, usually malignant neuroendocrine tumor arizing from delta cells. This neoplasm produces large amounts of somatostatin, which may result in a syndrome characterized by diarrhea, steatorrhea, weight loss, and gastric hyposecretion. Sixty percent are found in the pancreas and 40% in the duodenum or jejunum. The peak incidence occurs between 40 and 60 years of age; women are affected more than men by 2:1.
A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.
A parasomnia characterized by a partial arousal that occurs during stage IV of non-REM sleep. Affected individuals exhibit semipurposeful behaviors such as ambulation and are difficult to fully awaken. Children are primarily affected, with a peak age range of 4-6 years.
Mold and yeast inhibitor. Used as a fungistatic agent for foods, especially cheeses.
A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications.
An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias.
A condition resulting from infection with the second stage larvae of the parasite Spirometra.
A quinolizidine alkaloid isolated from several FABACEAE including LUPINUS; SPARTIUM; and CYTISUS. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest as an indicator of CYP2D6 genotype.
Motor hyperactivity with excessive movement of muscles of the body as a whole.
Any agent that prevents or relieves muscle spasms, mainly ones originating from smooth muscle contractions of the stomach, bladder and intestines.
Early infantile epileptic encephalopathy 1 (EIEE1) is a seizure disorder characterized by a type of seizure known as infantile spasms. The spasms usually appear before the age of 1. Several types of spasms have been described, but the most commonly reported type involves bending at the waist and neck and extending the arms and legs (sometimes called a jackknife spasm). Each spasm lasts only seconds, but they occur in clusters several minutes long. Although individuals do not usually have spasms while they are sleeping, the spasms commonly occur just after awakening. Infantile spasms usually stop by age 5, but many children then develop other types of seizures that recur throughout their lives.Most babies with EIEE1 have characteristic results on an electroencephalogram (EEG), a test used to measure the electrical activity of the brain. The EEG of these individuals typically shows an irregular pattern known as hypsarrhythmia, and this finding can help differentiate infantile spasms from other types of seizures.Because of the recurrent seizures, babies with EIEE1 stop developing normally and begin to lose skills they have acquired (developmental regression), such as sitting, rolling over, and babbling. Most affected individuals also have intellectual disability throughout their lives.
Mild or moderate loss of motor function accompanied by spasticity in the lower extremities. This condition is a manifestation of CENTRAL NERVOUS SYSTEM DISEASES that cause injury to the motor cortex or descending motor pathways.
Spasticity and weakness of the leg and hip muscles.
A group of inherited diseases that share similar phenotypes but are genetically diverse. Different genetic loci for autosomal recessive, autosomal dominant, and x-linked forms of hereditary spastic paraplegia have been identified. Clinically, patients present with slowly progressive distal limb weakness and lower extremity spasticity. Peripheral sensory neurons may be affected in the later stages of the disease. (J Neurol Neurosurg Psychiatry 1998 Jan;64(1):61-6; Curr Opin Neurol 1997 Aug;10(4):313-8)
A term referring to disorders characterized by the disruption of normal speech. It includes stuttering, lisps, dysarthria and voice disorders.
Instructional activity designed to teach patients how to vocalize with a non-functioning or absent larynx.
A method of speech used after laryngectomy, with sound produced by vibration of the column of air in the esophagus against the contracting cricopharyngeal sphincter. (Dorland, 27th ed)
Chemical substances with sperm immobilizing activity used as topically administered vaginal contraceptives.
An emergency condition caused by the twisting of the spermatic cord which contains the vessels that provide the blood supply to the testis and surrounding structures. It manifests with acute testicular pain. If immediate medical assistance is not provided, it will lead to necrosis and loss of the testicular tissue.
A benign cystic dilatation in the head of the epididymis that contains milky or watery fluid and spermatozoa.
A chemical product that is deleterious to sperms and can be in the form of either a jelly, foam, or cream.
Chemical substances which inhibit the process of spermatozoa formation at either the first stage, in which spermatogonia develop into spermatocytes and then into spermatids, or the second stage, in which spermatids transform into spermatozoa.
An acute or chronic inflammatory process affecting the mucous membrane of the sphenoid sinus.
Hereditary spherocytosis refers to a group of heterogeneous disorders that are characterized by the presence of spherical-shaped erythrocytes (spherocytes) on the peripheral blood smear. The disorders are characterized clinically by anemia, jaundice, and splenomegaly, with variable severity. Common complications include cholelithiasis, hemolytic episodes, and aplastic crises (review by Perrotta et al., 2008). Elgsaeter et al. (1986) gave an extensive review of the molecular basis of erythrocyte shape with a discussion of the role of spectrin and other proteins such as ankyrin, actin (102630), band 4.1 (130500), and band 3 (109270), all of which is relevant to the understanding of spherocytosis and elliptocytosis (see 611904). See Delaunay (2007) for a discussion of the molecular basis of hereditary red cell membrane disorders. Genetic Heterogeneity of Hereditary Spherocytosis Also see SPH2 (616649), caused by mutation in the SPTB gene (182870) on chromosome 14q23; SPH3 (270970), caused by mutation in the SPTA1 gene (182860) on chromosome 1q21; SPH4 (612653), caused by mutation in the SLC4A1 gene (109270) on chromosome 17q21; and SPH5 (612690), caused by mutation in the EPB42 gene (177070) on chromosome 15q15.
A group of inherited metabolic disorders characterized by the intralysosomal accumulation of SPHINGOLIPIDS primarily in the CENTRAL NERVOUS SYSTEM and to a variable degree in the visceral organs. They are classified by the enzyme defect in the degradation pathway and the substrate accumulation (or storage). Clinical features vary in subtypes but neurodegeneration is a common sign.
A form of spinal dysraphism associated with a protruding cyst made up of either meninges (i.e., a MENINGOCELE) or meninges in combination with spinal cord tissue (i.e., a MENINGOMYELOCELE). These lesions are frequently associated with spinal cord dysfunction, HYDROCEPHALUS, and SYRINGOMYELIA. (From Davis et al., Textbook of Neuropathology, 2nd ed, pp224-5)
Acute and chronic conditions characterized by external mechanical compression of the SPINAL CORD due to extramedullary neoplasm; EPIDURAL ABSCESS; SPINAL FRACTURES; bony deformities of the vertebral bodies; and other conditions. Clinical manifestations vary with the anatomic site of the lesion and may include localized pain, weakness, sensory loss, incontinence, and impotence.
An abnormality of the spinal cord (myelon).
The presence of an abnormal lateral curvature of the spine.
New abnormal growth of tissue in the SPINE.
Outgrowth of immature bony processes or bone spurs (OSTEOPHYTE) from the VERTEBRAE, reflecting the presence of degenerative disease and calcification. It commonly occurs in cervical and lumbar SPONDYLOSIS.
A heterogenous group of degenerative syndromes marked by progressive cerebellar dysfunction either in isolation or combined with other neurologic manifestations. Sporadic and inherited subtypes occur. Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked.
A spiro butyrophenone analog similar to HALOPERIDOL and other related compounds. It has been recommended in the treatment of SCHIZOPHRENIA.
Infections with bacteria of the order SPIROCHAETALES.
A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
A non-neoplastic or neoplastic disorder affecting the spleen. Examples include infection, hemangioma, lymphoma, leukemia and angiosarcoma.
Insufficiency of arterial or venous blood supply to the spleen due to emboli, thrombi, vascular torsion, or pressure that produces a macroscopic area of necrosis. (From Stedman, 25th ed)
A benign or malignant neoplasm that affects the spleen. Representative examples include hemangioma, lymphoma, splenic involvement by leukemia, and angiosarcoma.
Inflammation of the SPINE. This includes both arthritic and non-arthritic conditions.
A chronic inflammatory condition affecting the axial joints, such as the SACROILIAC JOINT and other intervertebral or costovertebral joints. It occurs predominantly in young males and is characterized by pain and stiffness of joints (ANKYLOSIS) with inflammation at tendon insertions.
A disorder of bone growth affecting the vertebrae and the ends of the long bones (epiphyses).
Spondylolisthesis is defined as forward slipping of a vertebral body on the one below it. Spondylolysis is defined as a defect in the pars interarticularis without vertebral slipping (summary by Wiltse et al., 1975).
A defect in the pars interarticularis of a vertebral bone.
A degenerative spinal disease that can involve any part of the VERTEBRA, the INTERVERTEBRAL DISK, and the surrounding soft tissue.
A form of spondylosis involving the INTERVERTEBRAL DISK, including both the annulus and the nucleus of the disk. It is usually the consequence of normal aging.
The commonest and least serious of the deep mycoses, characterized by nodular lesions of the cutaneous and subcutaneous tissues. It is caused by inhalation of contaminated dust or by infection of a wound with SPOROTHRIX.
A group of arthropod-borne diseases caused by spotted fever bio-group members of RICKETTSIA. They are characterized by fever, headache, and petechial (spotted) rash.
Deliberate severe and repeated injury to one domestic partner by the other.
A chronic malabsorption syndrome, occurring mainly in residents of or visitors to the tropics or subtropics. The failed INTESTINAL ABSORPTION of nutrients from the SMALL INTESTINE results in MALNUTRITION and ANEMIA that is due to FOLIC ACID deficiency.
A potent androgenic metabolite of TESTOSTERONE. It is produced by the action of the enzyme 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE.
A synthetic steroid that has anabolic and androgenic properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1194)
Gastroenteritis resulting from an infection with Staphylococcus Aureus.
Food poisoning that is caused by Staphylococcal infection.
Infections with bacteria of the genus STAPHYLOCOCCUS.
A blistering skin disorder caused by exfoliative toxins produced by Staphylococcus aureus infection. The toxins cause the formation of bullae and diffuse skin desquamation. The lesions may be localized or generalized, far away from the initial site of infection.
Infections to the skin caused by bacteria of the genus STAPHYLOCOCCUS.
A species of STAPHYLOCOCCUS that is a spherical, non-motile, gram-positive, chemoorganotrophic, facultative anaerobe. Mainly found on the skin and mucous membrane of warm-blooded animals, it can be primary pathogen or secondary invader.
Any of a group of polysaccharides of the general formula (C6-H10-O5)n, composed of a long-chain polymer of glucose in the form of amylose and amylopectin. It is the chief storage form of energy reserve (carbohydrates) in plants.
Lengthy and continuous deprivation of food. (Stedman, 25th ed)
A sudden intense and continuous aggravation of a state of asthma, marked by dyspnea to the point of exhaustion and collapse and not responding to the usual therapeutic efforts.
A life-threatening situation in which the brain is in a continuous state of seizure.
A saturated long-chain fatty acid with an 18-carbon backbone. Stearic acid is found in various animal and plant fats, and is a major component of cocoa butter and shea butter.
A disease of cats and mink characterized by a marked inflammation of adipose tissue and the deposition of ""ceroid"" pigment in the interstices of the adipose cells. It is believed to be caused by feeding diets containing too much unsaturated fatty acid and too little vitamin E. (Merck Veterinary Manual, 5th ed; Stedman, 25th ed)
A condition that is characterized by chronic fatty DIARRHEA, a result of abnormal DIGESTION and/or INTESTINAL ABSORPTION of FATS.
Persistent repetition of non-purposeful speech or movement.
A stereotypy is a repetitive, simple movement that can be voluntarily suppressed. Stereotypies are typically simple back-and-forth movements such as waving of flapping the hands or arms, and they do not involve complex sequences or movement fragments. Movement is often but not always rhythmic and may involve fingers, wrists, or more proximal portions of the upper extremity. The lower extremity is not typically involved. Stereotypies are more commonly bilateral than unilateral.
A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)
The increase in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical.
Abnormal distention of the STOMACH due to accumulation of gastric contents that may reach 10 to 15 liters. Gastric dilatation may be the result of GASTRIC OUTLET OBSTRUCTION; ILEUS; GASTROPARESIS; or denervation.
A non-neoplastic or neoplastic disorder that affects the stomach. Representative examples of non-neoplastic disorders include gastritis and gastric ulcer. Representative examples of neoplastic disorders include adenomas, carcinomas, and lymphomas.
In a review article on the genetic predisposition to gastric cancer, Bevan and Houlston (1999) concluded that several genes may be associated with an increased risk of gastric cancer. Gastric cancer is a manifestation of a number of inherited cancer predisposition syndromes, including hereditary nonpolyposis colon cancer (HNPCC1; see 120435), familial adenomatous polyposis (FAP; 175100), Peutz-Jeghers syndrome (PJS; 175200), Cowden disease (CD; 158350), and the Li-Fraumeni syndrome (151623). See also hereditary diffuse gastric cancer (HDGC; 137215). Canedo et al. (2007) provided a review of genetic susceptibility to gastric cancer in patients infected with Helicobacter pylori (see 600263).
An ulcer, that is, an erosion of an area of the gastric mucous membrane.
Twisting of the STOMACH that may result in gastric ISCHEMIA and GASTRIC OUTLET OBSTRUCTION. It is often associated with DIAPHRAGMATIC HERNIA.
INFLAMMATION of the soft tissues of the MOUTH, such as MUCOSA; PALATE; GINGIVA; and LIP.
A recurrent disease of the oral mucosa of unknown etiology. It is characterized by small white ulcerative lesions, single or multiple, round or oval, lasting for 7-14 days and healing without scarring.
Inflammation of the mouth due to denture irritation.
Stomatitis caused by Herpesvirus hominis. It usually occurs as acute herpetic stomatitis (or gingivostomatitis), an oral manifestation of primary herpes simplex seen primarily in children and adolescents.
Inflammation of the mouth mucosa associated with the presence of ulcers.
General or unspecified diseases of the stomatognathic system, comprising the mouth, teeth, jaws, and pharynx.
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Any of the several infectious disorders caused by members of streptococcus, a genus of gram positive bacteria belonging to the family Streptococcaceae. Streptococcal infections are classified into Groups A, B, C, D and G.
A mixture of the enzymes (streptokinase and streptodornase) produced by hemolytic streptococci. It is used topically on surface lesions and by instillation in closed body cavities to remove clotted blood or fibrinous or purulent accumulations. It is also used as a skin test antigen in evaluating generalized cell-mediated immunodeficiency. (Dorland, 27th ed) EC 3.-.
Streptococcal fibrinolysin . An enzyme produced by hemolytic streptococci. It hydrolyzes amide linkages and serves as an activator of plasminogen. It is used in thrombolytic therapy and is used also in mixtures with streptodornase (STREPTODORNASE AND STREPTOKINASE). EC 3.4.-.
The negative mental, emotional, and physical reactions that occur when environmental stressors are perceived as exceeding the individual's adaptive capacities.
A class of traumatic stress disorders with symptoms that last more than one month.
The involuntary loss of urine in females secondary to insufficient strength of the pelvic floor muscles; this can result from physical changes following pregnancy and childbirth, or as a response to a decrease in estrogen during menopause.
Anxiety disorders manifested by the development of characteristic symptoms following a psychologically traumatic event that is outside the normal range of usual human experience. Symptoms include re-experiencing the traumatic event, increased arousal, and numbing of responsiveness to or reduced involvement with the external world. Traumatic stress disorders can be further classified by the time of onset and the duration of these symptoms.
Stress wherein emotional factors predominate.
Narrowing or constriction of the inner surface (lumen) of an artery.
A symptom resulting from laryngeal obstruction. It is characterized by a high pitched breathing sound.
A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)
Infection of horses with parasitic nematodes of the superfamily STRONGYLOIDEA. Characteristics include the development of hemorrhagic nodules on the abdominal peritoneum.
An infection that is caused by nematodes of the genus Strongyloides, most commonly Strongyloides stercoralis, which is a soil-transmitted helminth, and which is characterized by a variety of gastrointestinal, dermatologic, and, occasionally, pulmonary manifestations. The worm's autoinfective life cycle can lead to hyper-infection and life-threatening dissemination in immunocompromised hosts decades after initial infection.
An element of the alkaline earth family of metals. It has the atomic symbol Sr, atomic number 38, and atomic weight 87.62.
A number of different cardioactive glycosides obtained from Strophanthus species. OUABAIN is from S. gratus and CYMARINE from S. kombe. They are used like the digitalis glycosides.
An ovarian mature teratoma characterized by the presence of aberrant thyroid tissue. The aberrant thyroid tissue shows morphologic changes identical to thyroid adenoma or carcinoma. Patients may present with abdominal mass and unusual symptoms due to thyrotoxicosis, or Meigs syndrome (ascites and pleural effusion).
Sturge-Weber syndrome is characterized by an intracranial vascular anomaly, leptomeningeal angiomatosis, most often involving the occipital and posterior parietal lobes. The most common symptoms and signs are facial cutaneous vascular malformations (port-wine stains), seizures, and glaucoma. Stasis results in ischemia underlying the leptomeningeal angiomatosis, leading to calcification and laminar cortical necrosis. The clinical course is highly variable and some children experience intractable seizures, mental retardation, and recurrent stroke-like episodes (review by Thomas-Sohl et al., 2004).
A disturbance in the normal fluency and time patterning of speech that is inappropriate for the individual's age. This disturbance is characterized by frequent repetitions or prolongations of sounds or syllables. Various other types of speech dysfluencies may also be involved including interjections, broken words, audible or silent blocking, circumlocutions, words produced with an excess of physical tension, and monosyllabic whole word repetitions. Stuttering may occur as a developmental condition in childhood or as an acquired disorder which may be associated with BRAIN INFARCTIONS and other BRAIN DISEASES. (From DSM-IV, 1994)
A rare, slowly progressive encephalitis caused by chronic infection with the MEASLES VIRUS. The condition occurs primarily in children and young adults, approximately 2-8 years after the initial infection. A gradual decline in intellectual abilities and behavioral alterations are followed by progressive MYOCLONUS; MUSCLE SPASTICITY; SEIZURES; DEMENTIA; autonomic dysfunction; and ATAXIA. DEATH usually occurs 1-3 years after disease onset. Pathologic features include perivascular cuffing, eosinophilic cytoplasmic inclusions, neurophagia, and fibrous gliosis. It is caused by the SSPE virus, which is a defective variant of MEASLES VIRUS. (From Adams et al., Principles of Neurology, 6th ed, pp767-8)
Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.
A clinically significant reduction in blood supply to the BRAIN STEM and CEREBELLUM (i.e., VERTEBROBASILAR INSUFFICIENCY) resulting from reversal of blood flow through the VERTEBRAL ARTERY from occlusion or stenosis of the proximal subclavian or brachiocephalic artery. Common symptoms include VERTIGO; SYNCOPE; and INTERMITTENT CLAUDICATION of the involved upper extremity. Subclavian steal may also occur in asymptomatic individuals. (From J Cardiovasc Surg 1994;35(1):11-4; Acta Neurol Scand 1994;90(3):174-8)
Bleeding beneath the mucous membrane that lines the inner surface of the eyelid.
Presence of air or gas in the subcutaneous tissues of the body.
An intracranial or rarely intraspinal suppurative process invading the space between the inner surface of the DURA MATER and the outer surface of the ARACHNOID.
A benign or malignant neoplasm that affects the sublingual gland.
Diseases involving the SUBMANDIBULAR GLAND.
A benign or malignant neoplasm that affects the submandibular gland.
Accumulation of purulent EXUDATES beneath the DIAPHRAGM, also known as upper abdominal abscess. It is usually associated with PERITONITIS or postoperative infections.
Abuse, overuse, or misuse of a substance by its injection into a vein.
A substance-specific organic brain syndrome that follows the discontinuation of administration or use, or reduction in intake of an addictive substance, e.g. opioids, barbiturates and alcohol; amphetamines or similarly acting sympathomimetics; cocaine; nicotine; sedatives, hypnotics, or anxiolytics. Syndrome manifests with diverse, often painful physical and psychological symptoms, which include but not limited to intense drug craving, anxiety, depression, insomnia, nausea, perspiration, body aches, tremors, hallucinations, and convulsions.
A set of opposing, nonequilibrium reactions catalyzed by different enzymes which act simultaneously, with at least one of the reactions driven by ATP hydrolysis. The results of the cycle are that ATP energy is depleted, heat is produced and no net substrate-to-product conversion is achieved. Examples of substrate cycling are cycling of gluconeogenesis and glycolysis pathways and cycling of the triglycerides and fatty acid pathways. Rates of substrate cycling may be increased many-fold in association with hypermetabolic states resulting from severe burns, cold exposure, hyperthyroidism, or acute exercise.
A benign lesion that affects the distal phalanx, most often the great toe. Grossly it consists of a cartilage cap and a bony stalk. Microscopically it is characterized by an osteochondromatous proliferation with a gradual transition of a peripheral spindle-cell proliferation to hyaline cartilage to trabecular bone. Pain and swelling are present. Simple resection is usually curative.
A thickening of the stratum corneum in the region beneath the nails.
A subclass of IMIDES with the general structure of pyrrolidinedione. They are prepared by the distillation of ammonium succinate. They are sweet-tasting compounds that are used as chemical intermediates and plant growth stimulants.
A quaternary ammonium compound and depolarizing agent with short-term muscle relaxant properties. Succinylcholine binds to nicotinic receptors at the neuromuscular junction and opening the ligand-gated channels in the same way as acetylcholine, resulting in depolarization and inhibition of neuromuscular transmission. Depolarization may be prolonged due to succinylcholine's resistance to acetylcholinesterases thereby leading to disorganized muscle contraction followed by skeletal muscle relaxation and flaccid paralysis.
A basic aluminum complex of sulfated sucrose.
A nonreducing disaccharide composed of GLUCOSE and FRUCTOSE linked via their anomeric carbons. It is obtained commercially from SUGARCANE, sugar beet (BETA VULGARIS), and other plants and used extensively as a food and a sweetener.
Sudden infant death syndrome (SIDS) is a diagnosis of exclusion which should be made only after a thorough autopsy without identification of a specific cause of death (Mage and Donner, 2004). Weese-Mayer et al. (2007) provided a detailed review of genetic factors that have been implicated in SIDS. The authors concluded that SIDS represents more than 1 entity and has a heterogeneous etiology most likely involving several different genetically controlled metabolic pathways.
A synthetic sulfanylacetamide derivative with bacteriostatic activity. Sulfacetamide inhibits bacterial folic acid synthesis by competing with para amino benzoic acid. With a broad spectrum of action, it is used as an anti-infective topical agent to treat skin infections and as an oral agent for urinary tract infections. (NCI04)
A broad-spectrum sulfanilamide and a synthetic analog of para-aminobenzoic acid (PABA) with bacteriostatic and antimalarial properties. Sulfadoxine competes with PABA for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. This leads to an inhibition of parasitic folic acid synthesis and de novo synthesis of purines and pyrimidines, ultimately resulting in cell growth arrest and cell death.
A long-acting sulfonamide antibiotic used for the treatment of chronic bronchitis, urinary tract infections and malaria.
A long-acting sulfanilamide antibacterial agent. Sulfamerazine inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for the binding site on dihydropteroate synthase.
A broad-spectrum sulfanilamide and a synthetic analog of para-aminobenzoic acid (PABA) with antibacterial property. Sulfamethizole competes with PABA for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. This leads to an inhibition of bacterial folic acid synthesis and de novo synthesis of purines and pyrimidines, ultimately resulting in cell growth arrest and cell death.
Compounds based on 4-aminobenzenesulfonamide. The '-anil-' part of the name refers to aniline.
A long-acting sulfonamide antibiotic used in the treatment of leprosy.
A sulfonamide antibiotic used in veterinary medicine and in the meat and poultry industries.
A short-acting sulfonamide antibiotic. Its use has been largely replaced with less toxic alternatives but is still used in combination with sulfacetamide and sulfabenzamide for the treatment of vaginal infections and for disinfecting home aquariums.
A morbid condition due to the presence of sulfmethemoglobin in the blood. It is marked by persistent cyanosis, but the blood count does not reveal any special abnormality in the blood. It is thought to be caused by the action of hydrogen sulfide absorbed from the intestine. (Stedman, 25th ed)
Chemical agents that react with SH groups. This is a chemically diverse group that is used for a variety of purposes. Among these are enzyme inhibition, enzyme reactivation or protection, and labelling.
A phenylbutazone derivative with uricosuric and antithrombotic properties. Sulfinpyrazone competitively inhibits reabsorption of urate at the proximal renal tubule in the kidney. This agent acts on the organic anion transport exchanger, thereby increasing uric acid excretion and decreasing serum uric acid levels resulting in the prevention of urate deposition. Sulfinpyrazone also blocks tubular excretion of various acidic drugs, resulting in increased serum concentration of the drugs. In addition, sulfinpyrazone and its active metabolite inhibit the synthesis of thromboxane A2, by competitively inhibiting the activity of cyclooxygenase, thereby preventing platelet aggregation through restoration of platelet survival time to normal, and decreasing platelet adhesiveness to subendothelial cells.
A broad-spectrum, short-acting sulfanilamide and a synthetic analog of para-aminobenzoic acid (PABA) with antibacterial property. Sulfisoxazole competes with PABA for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. This leads to an inhibition of bacterial folic acid synthesis and de novo synthesis of purines and pyrimidines, ultimately resulting in cell growth arrest and cell death.
A short-acting sulfonamide antibacterial agent with broad spectrum activity against both gram-negative and gram-positive bacteria.
A phenolphthalein that is used as a diagnostic aid in hepatic function determination.
A group of compounds that contain the structure SO2NH2.
Any of substance containing a sulfonyl functional group attached to two carbon atoms with antibiotic activity. Tthe general structural formula is R-S(=O)(=O)-R'.
compounds of the type R-SO2-NHCONH-; when R=Ph, these are a group of hypoglycemic agents which enhance insulin secretion by beta cells and insulin sensitivity in target tissue, and so are effective in type II (noninsulin-dependent) diabetes mellitus.
An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight [32.059; 32.076]. It is found in the amino acids cysteine and methionine.
A strong acid that, when concentrated is extremely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives.
A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.
A peripheral vasodilator that was formerly used in the management of peripheral and cerebral vascular disorders. It is hepatotoxic and fatalities have occurred. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1312)
A dopamine D2-receptor antagonist. It has been used therapeutically as an antidepressant, antipsychotic, and as a digestive aid. (From Merck Index, 11th ed)
A frequent complication of drug therapy for microbial infection. It may result from opportunistic colonization following immunosuppression by the primary pathogen and can be influenced by the time interval between infections, microbial physiology, or host resistance. Experimental challenge and in vitro models are sometimes used in virulence and infectivity studies.
A very rare syndrome characterized by compression of the third portion of the duodenum against the aorta. The compression is caused by the superior mesenteric artery. It results in complete or partial duodenal obstruction. Signs and symptoms include nausea, vomiting, abdominal pain and distention, failure to gain weight, and weight loss.
A condition that occurs when the obstruction of the thin-walled SUPERIOR VENA CAVA interrupts blood flow from the head, upper extremities, and thorax to the RIGHT ATRIUM. Obstruction can be caused by NEOPLASMS; THROMBOSIS; ANEURYSM; or external compression. The syndrome is characterized by swelling and/or CYANOSIS of the face, neck, and upper arms.
Occurrence or induction of release of more ova than are normally released at the same time in a given species. The term applies to both animals and humans.
An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide.
a second mutation occurring at a site different from the first mutation and able to mask or suppress the phenotypic expression of the first mutation; include (1) intragenic suppressor mutation within the same gene, and (2) intergenic suppressor mutation by a suppressor gene.
A rare late-onset neurodegenerative disease with characteristics of supranuclear gaze palsy, postural instability, progressive rigidity, and mild dementia. Five clinical variants have been described with clinicopathological correlations, with Richardson's syndrome the most common clinical variant. The disease has neuropathological manifestations of neuronal loss, gliosis with astrocytic plaques and accumulation of tau-immunoreactive neurofibrillary tangles in specific brain areas. The differences in the rate and areas of accumulation of phosphorylated tau protein correlate with the five clinical variants. The disease is a 4R tauopathy composed of a preponderance of four-repeat (exon 10 positive) tau isoforms and a characteristic biochemical profile (doublet tau 64 and tau 69). The MAPT H1-clade specific sub-haplotype, H1c, is a risk factor for this disease.
A benign or malignant neoplasm that occurs within the intracranial cavity above the tentorium cerebelli.
An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It inhibits prostaglandin synthesis and has been proposed as an anti-arthritic.
A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.
Disruption or deterioration of a surgical wound.
An infection that occurs at a surgical site within 30 days after an operation.
Congenital locomotor ataxia of lambs, thought to be associated with copper deficiency. It is characterized clinically by progressive incoordination of the hind limbs and pathologically by disruption of neuron and myelin development in the central nervous system. It is caused by a deficiency of metabolizable copper in the ewe during the last half of her pregnancy. (Dorland, 28th ed; Stedman, 26th ed)
A benign or malignant neoplasm arising from the sweat glands.
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
A febrile response accompanied by diaphoresis.
Gustatory sweating results from a disruption of the auriculotemporal nerve pathways. Damage to the nerve may cause a misdirected regrowth that results in parasympathetic innervation of sympathetic receptors and, therefore, facial sweating and flushing with gustatory stimulation (summary by Dunbar et al., 2002).
Enlargement; expansion in size; sign of inflammation
Diseases of domestic swine and of the wild boar of the genus Sus.
An acute and chronic contagious disease of young pigs caused by Erysipelothrix insidiosa.
An enterovirus infection of swine clinically indistinguishable from FOOT-AND-MOUTH DISEASE, vesicular stomatitis, and VESICULAR EXANTHEMA OF SWINE. It is caused by a strain of HUMAN ENTEROVIRUS B.
Drugs that inhibit the actions of the sympathetic nervous system by any mechanism. The most common of these are the ADRENERGIC ANTAGONISTS and drugs that deplete norepinephrine or reduce the release of transmitters from adrenergic postganglionic terminals (see ADRENERGIC AGENTS). Drugs that act in the central nervous system to reduce sympathetic activity (e.g., centrally acting alpha-2 adrenergic agonists, see ADRENERGIC ALPHA-AGONISTS) are included here.
Drugs that mimic the effects of stimulating postganglionic adrenergic sympathetic nerves. Included here are drugs that directly stimulate adrenergic receptors and drugs that act indirectly by provoking the release of adrenergic transmitters.
Abnormal anatomical or physiological conditions and objective or subjective manifestations of disease, not classified as disease or syndrome.
A spontaneous loss of consciousness caused by insufficient blood supply to the brain.
A congenital anomaly of the hand or foot, marked by the webbing between adjacent fingers or toes. Syndactylies are classified as complete or incomplete by the degree of joining. Syndactylies can also be simple or complex. Simple syndactyly indicates joining of only skin or soft tissue; complex syndactyly marks joining of bony elements.
Sympathetic alpha-adrenergic agonist with actions like PHENYLEPHRINE. It is used as a vasoconstrictor in circulatory failure, asthma, nasal congestion, and glaucoma.
A union between adjacent bones or parts of a single bone formed by osseous material, such as ossified connecting cartilage or fibrous tissue. (Dorland, 27th ed)
Synovial sarcomas, which represent approximately 10% of all soft tissue sarcomas, are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18)(p11.2;q11.2), which usually represents either of 2 gene fusions, SYT (600192)-SSX1 (312820) or SYT-SSX2 (300192), encoding putative transcriptional proteins differing at 13 amino acid positions (summary by Ladanyi et al., 2002). Synovial sarcoma, according to the experience of Enzinger and Weiss (1983), is the fourth most common type of soft tissue sarcoma. It usually develops in adolescents and young adults, is more common in males than in females, and has no racial predilection.
A locally aggressive, diffusely infiltrating tumor, arising in the tendon sheath. It is composed of synovial-like mononuclear cells, hemosiderin-laden macrophages, foam cells, and inflammatory cells. Multinucleated osteoclast-like giant cells are usually present, although in a minority of cases they may be absent or rare. It predominantly affects young adults. Symptoms include joint swelling, pain, and joint effusion.
small synthetic peptides that mimic surface antigens of pathogens and are immunogenic.
A contagious bacterial infection caused by the spirochete Treponema pallidum. It is a sexually transmitted disorder, although it can also be transmitted from the mother to the fetus in utero. Typically, it is initially manifested with a single sore which heals without treatment. If the infection is left untreated, the initial stage is followed by skin rash and mucous membrane lesions. A late stage follows, which is characterized by damage of the internal organs, including the nervous system.
Cardiovascular manifestations of SYPHILIS, an infection of TREPONEMA PALLIDUM. In the late stage of syphilis, sometimes 20-30 years after the initial infection, damages are often seen in the blood vessels including the AORTA and the AORTIC VALVE. Clinical signs include syphilitic aortitis, aortic insufficiency, or aortic ANEURYSM.
A life-threatening bacterial infection of the newborn caused by Treponema pallidum. It is transmitted to the infant from a mother with syphilis through the placenta during pregnancy. Signs and symptoms include irritability, fever, failure to thrive, saddle nose, cutaneous rash, and pneumonia.
Cutaneous lesions arising from infection with Treponema pallidum. In the primary stage, 18-21 days following infection, one or more chancres appear. If untreated, the subsequent stages of the disease appear as syphilids. These eruptions are superficial, nondestructive, exanthematic, transient, macular roseolas that may later be maculopapular or papular polymorphous or scaly, pustular, pigmented eruptions.(Arnold, Odom, and James, Andrew's Diseases of the Skin, 8th ed, p409)
A stage of syphilis characterized by the serologic evidence of infection by Treponema pallidum without evidence of accompanying signs or symptoms related to the disease.
A rare disorder characterized by the formation of a cyst in the spinal cord. It results in weakness, pain, and stiffness in the shoulders, arms, legs, or back. It may be associated with Chiari malformation. Other causes include spinal cord injury, inflammation, or tumor.
A form of neurosyphilis characterized by slowly progressive degeneration of the spinal cord. Signs and symptoms include pain, ataxia, loss of coordination, personality changes, blindness, urinary incontinence, dementia, and degeneration of the joints.
A rapid heartrate that exceeds the range of the normal resting heartrate for age.
Abnormally rapid heartbeats caused by reentry of atrial impulse into the dual (fast and slow) pathways of ATRIOVENTRICULAR NODE. The common type involves a blocked atrial impulse in the slow pathway which reenters the fast pathway in a retrograde direction and simultaneously conducts to the atria and the ventricles leading to rapid HEART RATE of 150-250 beats per minute.
A disorder characterized by an electrocardiographic finding of atrial tachycardia that does not originate from the sinoatrial node.
A rare form of supraventricular tachycardia caused by automatic, not reentrant, conduction initiated from sites at the atrioventricular junction, but not the ATRIOVENTRICULAR NODE. It usually occurs during myocardial infarction, after heart surgery, or in digitalis intoxication with a HEART RATE ranging from 140 to 250 beats per minute.
Abnormally rapid heartbeats with sudden onset and cessation.
Abnormally rapid heartbeats caused by reentry circuit in or around the SINOATRIAL NODE. It is characterized by sudden onset and offset episodes of tachycardia with a HEART RATE of 100-150 beats per minute. The P wave is identical to the sinus P wave but with a longer PR interval.
A disorder characterized by an electrocardiographic finding of abnormally rapid heart rate with its origin in the sinus node. Thresholds for different age, gender, and patient populations exist. (CDISC)
A disorder characterized by an electrocardiographic finding of a tachycardia which does not originate in the ventricles or His Purkinje system. There is an abnormally high heart rate and QRS complexes are typically narrow, but aberration or preexcitation may be present. (CDISC)
A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.
A parasitic infection caused by tapeworms of the genus Taenia. Humans are infected by eating undercooked or raw meat of infected animals. It is usually an asymptomatic infection and patients may become aware of the infection by noticing segments of the tapeworm in their feces. If symptoms are present, they include nausea, abdominal pain, indigestion, constipation, or diarrhea.
A chronic inflammatory process that affects the AORTA and its primary branches, such as the brachiocephalic artery (BRACHIOCEPHALIC TRUNK) and CAROTID ARTERIES. It results in progressive arterial stenosis, occlusion, and aneurysm formation. The pulse in the arm is hard to detect. Patients with aortitis syndrome often exhibit retinopathy.
Finely powdered native hydrous magnesium silicate. It is used as a dusting powder, either alone or with starch or boric acid, for medicinal and toilet preparations. It is also an excipient and filler for pills, tablets, and for dusting tablet molds. (From Merck Index, 11th ed)
A foot deformity in which the arch of the foot is high and often the heel adducted.
An antineoplastic nonsteroidal selective estrogen receptor modulator (SERM). Tamoxifen competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. In addition, tamoxifen up-regulates the production of transforming growth factor B (TGFb), a factor that inhibits tumor cell growth, and down-regulates insulin-like growth factor 1 (IGF-1), a factor that stimulates breast cancer cell growth.
Tangier disease is an autosomal recessive disorder characterized by markedly reduced levels of plasma high density lipoproteins (HDL) resulting in tissue accumulation of cholesterol esters. Clinical features include very large, yellow-orange tonsils, enlarged liver, spleen and lymph nodes, hypocholesterolemia, and abnormal chylomicron remnants (Brooks-Wilson et al., 1999).
Polyphenolic compounds with molecular weights of around 500-3000 daltons and containing enough hydroxyl groups (1-2 per 100 MW) for effective cross linking of other compounds (ASTRINGENTS). The two main types are HYDROLYZABLE TANNINS and CONDENSED TANNINS. Historically, the term has applied to many compounds and plant extracts able to render skin COLLAGEN impervious to degradation. The word tannin derives from the Celtic word for OAK TREE which was used for leather processing.
A syndrome resulting from the entrapment and compression of the tibial nerve. Signs and symptoms include burning sensation, tingling, and pain in the foot sole.
Conditions characterized by an alteration in gustatory function or perception. Taste disorders are frequently associated with OLFACTION DISORDERS. Additional potential etiologies include METABOLIC DISEASES; DRUG TOXICITY; and taste pathway disorders (e.g., TASTE BUD diseases; FACIAL NERVE DISEASES; GLOSSOPHARYNGEAL NERVE DISEASES; and BRAIN STEM diseases).
A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids.
A bile salt formed in the liver by conjugation of chenodeoxycholate with taurine, usually as the sodium salt. It acts as detergent to solubilize fats in the small intestine and is itself absorbed. It is used as a cholagogue and choleretic.
The product of conjugation of cholic acid with taurine. Its sodium salt is the chief ingredient of the bile of carnivorous animals. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and cholerectic.
A bile salt formed in the liver by conjugation of deoxycholate with taurine, usually as the sodium salt. It is used as a cholagogue and choleretic, also industrially as a fat emulsifier.
A bile salt formed in the liver from lithocholic acid conjugation with taurine, usually as the sodium salt. It solubilizes fats for absorption and is itself absorbed. It is a cholagogue and choleretic.
Hexosaminidase A deficiency results in a group of neurodegenerative disorders caused by intralysosomal storage of the specific glycosphingolipid, GM2 ganglioside. The prototype hexosaminidase A deficiency is Tay-Sachs disease, also known as the acute infantile variant. Tay-Sachs disease is characterized by progressive weakness, loss of motor skills, decreased attentiveness, and increased startle response beginning between ages three and six months with progressive evidence of neurodegeneration including: seizures, blindness, spasticity, eventual total incapacitation, and death, usually before age four years. The juvenile (subacute), chronic, and adult-onset variants of hexosaminidase A deficiency have later onsets, slower progression, and more variable neurologic findings, including: progressive dystonia, spinocerebellar degeneration, motor neuron disease, and, in some individuals with adult-onset disease, a bipolar form of psychosis.
An expected condition experienced by children during the emergence of deciduous teeth. Though a full set of 20 primary teeth takes more than two years to emerge, teething syndrome may be variably noted from the first paired eruption (usually at the sixth month) until the last. Characteristically, irritability, inflamed gingivae, drooling and chewing on solid objects may be seen several days prior to the eruption with rapid resolution. Typically, the lower central incisors appear first followed by the upper central incisors. Molars and canine teeth are the last to erupt. Anecdotal associations with fever and diarrhea are misattributed.
An autosomal dominant hereditary disorder caused by mutations in the ACVRL1, ENG, and SMAD4 genes. It is characterized by the presence of telangiectasias in the skin, mucous membranes, lungs, brain, liver, and gastrointestinal tract. It results in hemorrhages from the affected areas.
Local dilatation of small vessels resulting in red discoloration of the skin or mucous membranes.
A benzodiazepine derivative with antidepressant, sedative, hypnotic and anticonvulsant properties. Temazepam potentiates the inhibitory activities of gamma-aminobutyric acid (GABA) by binding to the GABA receptor, located in the limbic, neocortical and mesencephalic reticular system. This increases the frequency of chloride channel opening events, allowing the flow of chloride ions into the neuron leading to membrane hyperpolarization and decreases neuronal excitability.
A systemic autoimmune disorder that typically affects medium and large ARTERIES, usually leading to occlusive granulomatous vasculitis with transmural infiltrate containing multinucleated GIANT CELLS. The TEMPORAL ARTERY is commonly involved. This disorder appears primarily in people over the age of 50. Symptoms include FEVER; FATIGUE; HEADACHE; visual impairment; pain in the jaw and tongue; and aggravation of pain by cold temperatures. (From Adams et al., Principles of Neurology, 6th ed)
A variety of conditions affecting the anatomic and functional characteristics of the temporomandibular joint. Factors contributing to the complexity of temporomandibular diseases are its relation to dentition and mastication and the symptomatic effects in other areas which account for referred pain to the joint and the difficulties in applying traditional diagnostic procedures to temporomandibular joint pathology where tissue is rarely obtained and x-rays are often inadequate or nonspecific. Common diseases are developmental abnormalities, trauma, subluxation, luxation, arthritis, and neoplasia. (From Thoma's Oral Pathology, 6th ed, pp577-600)
A common disorder noted with jaw movement. It may be caused by malocclusion, repetitive use injury, trauma or arthritis. It is more prevalent among females between their second and fourth decades. Clinical signs include preauricular pain, temporomandibular joint clicking (as the mandibular condyle slips from the articulation made with the capsular disc and temporal bone) and restriction of jaw motion. Clinical course is typically benign but may progress to associated headaches, ear and neck pain, tinnitus and dislocation of temporomandibular joint. Prognosis is favorable as a majority of cases will respond to conservative management.
Acute tendon injury accompanied by inflammation.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.
A condition characterized by pain in or near the lateral humeral epicondyle or in the forearm extensor muscle mass as a result of unusual strain. It occurs due repetitive stresses on the elbow from activities such as tennis playing.
Inflammation of the synovial lining of a tendon sheath. Causes include trauma, tendon stress, bacterial disease (gonorrhea, tuberculosis), rheumatic disease, and gout. Common sites are the hand, wrist, shoulder capsule, hip capsule, hamstring muscles, and Achilles tendon. The tendon sheaths become inflamed and painful, and accumulate fluid. Joint mobility is usually reduced.
An insect chemosterilant and an antineoplastic agent.
A synthetic nonapeptide (Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) which is identical to the peptide from the venom of the snake, Bothrops jararaca. It inhibits kininase II and ANGIOTENSIN I and has been proposed as an antihypertensive agent.
A non-seminomatous germ cell tumor characterized by the presence of various tissues which correspond to the different germinal layers (endoderm, mesoderm, and ectoderm). It occurs in the testis, ovary, and extragonadal sites including central nervous system, mediastinum, lung, and stomach. According to the level of differentiation of the tissues which comprise the tumor, teratomas are classified as mature or immature. Mature teratomas are composed of well differentiated, adult-type tissues. Immature teratomas are composed of immature, fetal-type tissues. Testicular teratomas in children follow a benign clinical course. Mature ovarian teratomas without a fetal-type component have an excellent outcome. The prognosis of immature ovarian teratomas is related to the grade and stage of the tumor.
A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.
The sulfate salt form of terbutaline, an ethanolamine derivative with bronchodilating and tocolytic properties. Terbutaline sulfate selectively binds to and activates beta-2 adrenergic receptors, leading to intracellular adenyl cyclase activation via a trimeric G protein and subsequent increase in cyclic cAMP production. Increased cAMP levels result in relaxation of bronchial and vascular smooth muscle mediated through the activation of protein kinase A (PKA), which phosphorylates proteins in control of muscle tone. cAMP also inhibits calcium ion release from intracellular stores, reduces calcium entry into cells and induces the sequestration of intracellular calcium all of which aids the relaxation of airway muscles. Terbutaline sulfate also increases mucociliary clearance and reduces release of inflammatory cell mediators.
A non-neoplastic or neoplastic disorder affecting the testis. Representative examples include torsion, infarction, germ cell tumor, sex cord-stromal tumor, lymphoma, and leukemia.
Androgen insensitivity syndrome (AIS) is typically characterized by evidence of feminization (i.e., undermasculinization) of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46,XY karyotype. AIS represents a spectrum of defects in androgen action and can be subdivided into three broad phenotypes: Complete androgen insensitivity syndrome (CAIS), with typical female external genitalia. Partial androgen insensitivity syndrome (PAIS) with predominantly female, predominantly male, or ambiguous external genitalia. Mild androgen insensitivity syndrome (MAIS) with typical male external genitalia.
A benign or malignant neoplasm that affects the testis. Representative examples include fibroma, thecoma, benign Sertoli cell tumor, seminoma, embryonal carcinoma, sarcoma, leukemia, and lymphoma.
A progesterone derivative with antineoplastic activity. Testolactone inhibits steroid aromatase, thereby preventing the formation of estrogen from adrenal androstenedione and reducing endogenous estrogen levels. (NCI04)
A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.
A short acting oil-based injectable formulation of testosterone. Testosterone inhibits gonadotropin secretion from the pituitary gland and ablates estrogen production in the ovaries, thereby decreasing endogenous estrogen levels. In addition, this agent promotes the maintenance of male sex characteristics and is indicated for testosterone replacement in hypogonadal males. (NCI04)
A disease caused by tetanospasmin, a powerful protein toxin produced by CLOSTRIDIUM TETANI. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form.
An antitoxin used for the treatment of TETANUS.
Protein synthesized by CLOSTRIDIUM TETANI as a single chain of ~150 kDa with 35% sequence identity to BOTULINUM TOXIN that is cleaved to a light and a heavy chain that are linked by a single disulfide bond. Tetanolysin is the hemolytic and tetanospasmin is the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal CONVULSIONS.
A condition characterized by intermittent involuntary contraction of muscles (spasms) related to hypocalcemia or occasionally magneisum deficiency.
A drug formerly used as an antipsychotic and treatment of various movement disorders. Tetrabenazine blocks neurotransmitter uptake into adrenergic storage vesicles and has been used as a high affinity label for the vesicle transport system.
A benzoate ester with anesthetic properties. Upon administration, tetracaine reversibly binds voltage-gated sodium ion channels in neuronal cell membranes and inhibits sodium influx. This prevents the initiation and conduction of nerve impulses, and stabilizes neuronal membranes. This results in a loss of sensation, and thereby provides analgesia and anesthesia.
2,3,7,8-Tetrachlorodibenzo-p-dioxin which is often referred to simply as dioxin and is the reference for a number of compounds which are similar structurally and have dioxin-like toxicity. A substance extremely toxic to mammals, with a wide variation in sensitivity among species. Longer-term exposure of test mammals to lesser amounts can affect reproduction, cause birth defects, damage the liver and suppress the immune system. Several studies suggest that exposure to TCDD increases the risk of several types of cancer in people. Animal studies have also shown an increased risk of cancer from exposure to TCDD. The WHO and the USA DHHS have determined that TCDD is a human carcinogen. (NCI)
A phorbol ester with potential antineoplastic effects. Tetradecanoylphorbol acetate (TPA) induces maturation and differentiation of hematopoietic cell lines, including leukemic cells. This agent may induce gene expression and protein kinase C (PKC) activity. In addition to potential antineoplastic effects, TPA may exhibit tumor promoting activity. (NCI04)
L-Tryptophyl-L-methionyl-L-aspartyl-L-phenylalaninamide. The C-terminal tetrapeptide of gastrin. It is the smallest peptide fragment of gastrin which has the same physiological and pharmacological activity as gastrin.
A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound.
A synthetic pyrimidine nucleoside analogue with biomodulating activity. Tetrahydrouridine increases the efficacy of the radiosensitizer cytochlor (5-chloro-2'-deoxycytidine) by inhibiting the enzyme deoxycytidine monophosphate (dCMP) deaminase and preventing the premature deamination of the cytochlor metabolite 5-chloro-2'-deoxycytidine monophosphate (CldCMP) to 5-chloro-2'-deoxyuridine monophosphate (CldUMP); in turn, this increases tumor concentrations of CldUMP which is then further anabolized and incorporated selectively into tumor DNA as CldU (5-chloro-2'-deoxyuridine). (NCI04)
N,N',N'',N'''-Tetraisopropylpyrophosphamide. A specific inhibitor of pseudocholinesterases. It is commonly used experimentally to determine whether pseudo- or acetylcholinesterases are involved in an enzymatic process.
Critical congenital heart disease (CCHD) is a term that refers to a group of serious heart defects that are present from birth. These abnormalities result from problems with the formation of one or more parts of the heart during the early stages of embryonic development. CCHD prevents the heart from pumping blood effectively or reduces the amount of oxygen in the blood. As a result, organs and tissues throughout the body do not receive enough oxygen, which can lead to organ damage and life-threatening complications. Individuals with CCHD usually require surgery soon after birth.Although babies with CCHD may appear healthy for the first few hours or days of life, signs and symptoms soon become apparent. These can include an abnormal heart sound during a heartbeat (heart murmur), rapid breathing (tachypnea), low blood pressure (hypotension), low levels of oxygen in the blood (hypoxemia), and a blue or purple tint to the skin caused by a shortage of oxygen (cyanosis). If untreated, CCHD can lead to shock, coma, and death. However, most people with CCHD now survive past infancy due to improvements in early detection, diagnosis, and treatment.Some people with treated CCHD have few related health problems later in life. However, long-term effects of CCHD can include delayed development and reduced stamina during exercise. Adults with these heart defects have an increased risk of abnormal heart rhythms, heart failure, sudden cardiac arrest, stroke, and premature death.Each of the heart defects associated with CCHD affects the flow of blood into, out of, or through the heart. Some of the heart defects involve structures within the heart itself, such as the two lower chambers of the heart (the ventricles) or the valves that control blood flow through the heart. Others affect the structure of the large blood vessels leading into and out of the heart (including the aorta and pulmonary artery). Still others involve a combination of these structural abnormalities.People with CCHD have one or more specific heart defects. The heart defects classified as CCHD include coarctation of the aorta, double-outlet right ventricle, D-transposition of the great arteries, Ebstein anomaly, hypoplastic left heart syndrome, interrupted aortic arch, pulmonary atresia with intact septum, single ventricle, total anomalous pulmonary venous connection, tetralogy of Fallot, tricuspid atresia, and truncus arteriosus.
A sulfuric acid dimer, formed by disulfide linkage. This compound has been used to prolong coagulation time and as an antidote in cyanide poisoning.
A disorder of the thalamus. Causes include brain neoplasms, cerebrovascular disorders, brain trauma, brain hypoxia, infections, and brain hemorrhage. Signs and symptoms include movement and sensory abnormalities, visual abnormalities, ataxia, and coma.
A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia.
A natural aporphine benzylisoquinoline vinca alkaloid with antineoplastic activity. Thalicarpine binds to and inhibits p-glycoprotein, the multidrug resistance efflux pump. Thalicarpine also induces single-strand breaks in DNA and arrests cancer cells at the G2/M and G1 phase of the cell cycle. (NCI04)
A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.
A severe autosomal dominant inherited disorder caused by mutations in the FGFR3 gene. It is characterized by multiple skeletal abnormalities, including extremely short limbs. It results in the death of the neonate.
A drug that is derived from opium, which contains from 0.3-1.5% thebaine depending on its origin. It produces strychnine-like convulsions rather than narcosis. It may be habit-forming and is a controlled substance (opiate) listed in the U.S. Code of Federal Regulations, Title 21 Part 1308.12 (1985). (From Merck Index, 11th ed)
An ovarian or testicular stromal tumor characterized by the presence of lipid-rich neoplastic spindle cells. In females, uterine bleeding is the most common symptom. A minority of post-menopausal women with thecoma have an associated endometrial adenocarcinoma or rarely a malignant mixed mullerian tumor or endometrial stromal sarcoma. Rare cases with nuclear atypia and mitotic activity may metastasize. In males, thecomas are rare and they usually present as slow growing, sometimes painful masses. Metastases have not been reported.
Infection of cattle, sheep, or goats with protozoa of the genus THEILERIA. This infection results in an acute or chronic febrile condition.
Chelating agent and inhibitor of cellular respiration.
3,7-Dimethylxanthine. The principle alkaloid in Theobroma cacao (the cacao bean) and other plants. A xanthine alkaloid that is used as a bronchodilator and as a vasodilator. It has a weaker diuretic activity than THEOPHYLLINE and is also a less powerful stimulant of smooth muscle. It has practically no stimulant effect on the central nervous system. It was formerly used as a diuretic and in the treatment of angina pectoris and hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, pp1318-9)
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
2-Substituted benzimidazole first introduced in 1962. It is active against a variety of nematodes and is the drug of choice for STRONGYLOIDIASIS. It has CENTRAL NERVOUS SYSTEM side effects and hepatototoxic potential. (From Smith and Reynard, Textbook of Pharmacology, 1992, p919)
A thiosemicarbazone antimycobacterial agent with activity against isoniazid-resistant strains of Mycobacterium tuberculosis.
A nutritional condition produced by a deficiency of THIAMINE in the diet, characterized by anorexia, irritability, and weight loss. Later, patients experience weakness, peripheral neuropathy, headache, and tachycardia. In addition to being caused by a poor diet, thiamine deficiency in the United States most commonly occurs as a result of alcoholism, since ethanol interferes with thiamine absorption. In countries relying on polished rice as a dietary staple, BERIBERI prevalence is very high. (From Cecil Textbook of Medicine, 19th ed, p1171)
The coenzyme form of Vitamin B1 present in many animal tissues. It is a required intermediate in the PYRUVATE DEHYDROGENASE COMPLEX and the KETOGLUTARATE DEHYDROGENASE COMPLEX.
A barbiturate that is administered intravenously for the production of complete anesthesia of short duration, for the induction of general anesthesia, or for inducing a hypnotic state. (From Martindale, The Extra Pharmacopoeia, 30th ed, p919)
A dopamine antagonist that is particularly useful in treating the nausea and vomiting associated with anesthesia, mildly emetic cancer chemotherapy agents, radiation therapy, and toxins. This piperazine phenothiazine does not prevent vertigo or motion sickness. (From AMA Drug Evaluations Annual, 1994, p457)
An ethylmercury-sulfidobenzoate that has been used as a preservative in VACCINES; ANTIVENINS; and OINTMENTS. It was formerly used as a topical antiseptic. It degrades to ethylmercury and thiosalicylate.
A state of insufficient flesh on the body usually defined as having a body weight less than skeletal and physical standards. Depending on age, sex, and genetic background, a BODY MASS INDEX of less than 18.5 is considered as underweight.
A polyfunctional, organophosphorus alkylating agent and a stable derivative of N,N',N''-triethylenephosphoramide (TEPA), with antineoplastic activity. Upon administration, thiotepa is converted into highly reactive ethylenimine groups, which covalently bind to nucleophilic groups in DNA and demonstrate a preference for the N7 position of guanine bases. This induces crosslinking of alkylated guanine bases in double-stranded DNA, interferes with both DNA replication and cell division, and results in both the induction of apoptosis and the inhibition of cell growth.
A synthetic guanosine analogue antimetabolite. Phosphorylated by hypoxanthine-guanine phosphoribosyltransferase, thioguanine incorporates into DNA and RNA, resulting in inhibition of DNA and RNA syntheses and cell death. This agent also inhibits glutamine-5-phosphoribosylpyrophosphate amidotransferase, thereby inhibiting purine synthesis. (NCI04)
A sulfhydryl analog of inosine and an antimetabolite with potential antineoplastic and immunosuppressive properties. Thioinosine interferes with de novo purine synthesis and perturbs the pool of nucleotides necessary for DNA replication. As a result, this agent inhibits DNA synthesis, blocks cellular proliferation and induces apoptosis.
A barbiturate that is administered intravenously for the induction of general anesthesia or for the production of complete anesthesia of short duration.
A phenothiazine antipsychotic used in the management of PHYCOSES, including SCHIZOPHRENIA.
A potent inhibitor of membrane metalloendopeptidase (ENKEPHALINASE). Thiorphan potentiates morphine-induced ANALGESIA and attenuates naloxone-precipitated withdrawal symptoms.
A thioxanthene derivative and a dopamine antagonist with antipsychotic property. Thiothixene blocks postsynaptic dopamine receptors in the mesolimbic system and medullary chemoreceptor trigger zone, thereby decreasing dopamine activity leading to decreased stimulation of the vomiting center and psychotic effects, such as hallucinations and delusions. In addition, this agent blocks the D2 somatodendritic autoreceptor, thereby increasing dopamine turnover. Thiothixene possesses weak affinity for the histamine H1 and alpha-adrenergic receptors.
A sulfur-containing uracil. An established antithyroid drug and highly selective inhibitor of nitric oxide synthase (NOS), thiouracil also covalently binds to dopaquinone, produced by tyrosinase catalyzed oxidation of tyrosine, thereby selectively accumulating in de novo-synthesized melanin in overactive melanin-producing cells and providing a means to localize melanoma cells. (NCI04)
A photoactivable URIDINE analog that is used as an affinity label.
Compounds with three aromatic rings in linear arrangement with a SULFUR in the center ring.
A closed sac-like structure originating from the pleura that contains a liquid, gaseous, or semisolid substance.
A non-neoplastic or neoplastic disorder that affects the thorax and/or the organs of the thoracic cavity. Representative examples include pleural infection, mediastinitis, thymoma, mediastinal lymphoma, and pleural mesothelioma.
A benign or malignant, primary or metastatic neoplasm involving the tissues of the thorax.
A neurovascular syndrome associated with compression of the BRACHIAL PLEXUS; SUBCLAVIAN ARTERY; and SUBCLAVIAN VEIN at the superior thoracic outlet. This may result from a variety of anomalies such as a CERVICAL RIB, anomalous fascial bands, and abnormalities of the origin or insertion of the anterior or medial scalene muscles. Clinical features may include pain in the shoulder and neck region which radiates into the arm, PARESIS or PARALYSIS of brachial plexus innervated muscles, PARESTHESIA, loss of sensation, reduction of arterial pulses in the affected extremity, ISCHEMIA, and EDEMA. (Adams et al., Principles of Neurology, 6th ed, pp214-5).
An essential amino acid in humans (provided by food), Threonine is an important residue of many proteins, such as tooth enamel, collagen, and elastin. An important amino acid for the nervous system, threonine also plays an important role in porphyrin and fat metabolism and prevents fat buildup in the liver. Useful with intestinal disorders and indigestion, threonine has also been used to alleviate anxiety and mild depression. (NCI04)
Glanzmann thrombasthenia is an autosomal recessive bleeding disorder characterized by failure of platelet aggregation and by absent or diminished clot retraction. The abnormalities are related to quantitative or qualitative abnormalities of the GPIIb/IIIa platelet surface fibrinogen receptor complex resulting from mutations in either the GPIIb or GPIIIa genes (Rosenberg et al., 1997). See 187800 for discussion of a possible dominant form.
An enzyme formed from PROTHROMBIN that converts FIBRINOGEN to FIBRIN.
A non-atherosclerotic, inflammatory thrombotic disease that commonly involves small and medium-sized arteries or veins in the extremities. It is characterized by occlusive THROMBOSIS and FIBROSIS in the vascular wall leading to digital and limb ISCHEMIA and ulcerations. Thromboangiitis obliterans is highly associated with tobacco smoking.
A chronic myeloproliferative neoplasm that involves primarily the megakaryocytic lineage. It is characterized by sustained thrombocytosis in the blood, increased numbers of large, mature megakaryocytes in the bone marrow, and episodes of thrombosis and/or hemorrhage. (WHO, 2008)
A reduction in the number of circulating thrombocytes.
Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream.
Inflammation of a vein associated with a blood clot (THROMBUS).
Formation and development of a thrombus or blood clot in the blood vessel.
A thymus-dependent nonapeptide found in normal blood. Stimulates the formation of E rosettes and is believed to be involved in T-cell differentiation.
A phenol obtained from thyme oil or other volatile oils used as a stabilizer in pharmaceutical preparations, and as an antiseptic (antibacterial or antifungal) agent. It was formerly used as a vermifuge.
A neoplasm arising from the epithelial cells of the thymus. Although thymomas are usually encapsulated tumors, they may invade the capsule and infiltrate the surrounding tissues or even metastasize to distant anatomic sites. The following morphologic subtypes are currently recognized: type A, type B, type AB, metaplastic, micronodular, microscopic, and sclerosing thymoma. Thymomas type B are further subdivided into types B1, B2, and B3. Thymoma type B3 usually has the most aggressive clinical course.
A thymoma that is completely surrounded by a capsule, without evidence of capsular invasion, infiltration of the surrounding tissues, and metastases.
An alpha-adrenergic blocking agent that is used in Raynaud's disease. It is also used locally in the eye to reverse the mydriasis caused by phenylephrine and other sympathomimetic agents. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1312)
Thyroglobulin (2768 aa, ~305 kDa) is encoded by the human TG gene. This protein is involved in thyroid hormone synthesis.
A congenital benign cyst arising from the remnants of the thyroglossal duct. It is usually located in the midline of the neck.
A pharmacological agent that acts as a thyroid hormone antagonist. Antithyroid agents may inhibit thyroid hormone production.
A dangerous life-threatening hypermetabolic condition characterized by high FEVER and dysfunction of the cardiovascular, the nervous, and the gastrointestinal systems.
A dehydrated extract of thyroid glands from domesticated animals. After the removal of fat and connective tissue, the extract is dried or lyophilized to yield a yellowish to buff-colored amorphous powder containing 0.17-0.23% of iodine.
A benign or malignant neoplasm affecting the thyroid gland.
A nodular lesion that develops in the thyroid gland. Causes include adenoma, thyroiditis, fluid-filled cyst, multinodular goiter, and carcinoma.
Self-limited inflammation of the thyroid gland characterized by the presence of multinucleated giant cells. Patients present with neck pain, often associated with fever and dysphagia. The clinical course includes an initial phase of hyperthyroidism, followed by a phase of hypothyroidism, and eventually a return to normal thyroid function.
Acute inflammatory disease of the THYROID GLAND due to infections by BACTERIA; FUNGI; or other microorganisms. Symptoms include tender swelling, FEVER, and often with LEUKOCYTOSIS.
A hypermetabolic syndrome caused by excess THYROID HORMONES which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid HYPERPLASIA; THYROID NEOPLASMS; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by NERVOUSNESS; TACHYCARDIA; FATIGUE; WEIGHT LOSS; heat intolerance; and excessive SWEATING.
A glycoprotein hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Thyrotropin stimulates THYROID GLAND by increasing the iodide transport, synthesis and release of thyroid hormones (THYROXINE and TRIIODOTHYRONINE). Thyrotropin consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the pituitary glycoprotein hormones (TSH; LUTEINIZING HORMONE and FSH), but the beta subunit is unique and confers its biological specificity.
A tripeptide that stimulates the release of THYROTROPIN and PROLACTIN. It is synthesized by the neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, TRH (was called TRF) stimulates the release of TSH and PRL from the ANTERIOR PITUITARY GLAND.
A hormone synthesized and secreted by the thyroid gland containing four iodine atoms and is converted to triiodothyronine (T3) in the body, influencing metabolism and organ function.
Disorders characterized by recurrent TICS that may interfere with speech and other activities. Tics are sudden, rapid, nonrhythmic, stereotyped motor movements or vocalizations which may be exacerbated by stress and are generally attenuated during absorbing activities. Tic disorders are distinguished from conditions which feature other types of abnormal movements that may accompany another another condition. (From DSM-IV, 1994)
Infestations with soft-bodied (Argasidae) or hard-bodied (Ixodidae) ticks.
Paralysis caused by a neurotropic toxin secreted by the salivary glands of ticks.
Toxicoses caused by toxic substances secreted by the salivary glands of ticks; include tick paralysis (neurotropic toxin), sweating sickness (dermotropic toxin), and Rhipicephalus appendiculatus toxicosis (leukotropic toxin).
A thienopyridine derivative with anticoagulant activity. Ticlopidine inhibits adenosine-diphosphate (ADP) binding to its platelet receptor. This prevents ADP activation and inhibits platelet expression of the glycoprotein (GP) IIb/IIIA receptors, binding of fibrinogen to platelet glycoprotein GP IIb-IIIa and platelet-platelet interaction. This results in increased bleeding time.
A novel diuretic with uricosuric action. It has been proposed as an antihypertensive agent.
Idiopathic painful nonsuppurative swellings of one or more costal cartilages, especially of the second rib. The anterior chest pain may mimic that of coronary artery disease. (Dorland, 27th ed.)
Proposed anesthetic with possible anticonvulsant and sedative properties.
An opioid analgesic used similarly to MORPHINE in the control of moderate to severe pain. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1097)
A orally available small molecule interferon inducer that is used as an antiviral agent.
A beta-adrenergic antagonist that is similar in action to PROPRANOLOL; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor.
Ringworm of the scalp and associated hair mainly caused by species of MICROSPORUM; TRICHOPHYTON; and EPIDERMOPHYTON, which may occasionally involve the eyebrows and eyelashes.
A disease of the scalp that may affect the glabrous skin and the nails and is recognized by the concave sulfur-yellow crusts that form around loose, wiry hairs. Atrophy ensues, leaving a smooth, glossy, thin, paper-white patch. This type of disease is rare in the United States and more frequently seen in the Middle East, Africa, Southeastern Europe, and other countries bordering the Mediterranean Sea. (Arnold, Odom, and James, Andrew's Diseases of the Skin, 8th ed, p319)
Dermatological pruritic lesion in the feet, caused by Trichophyton rubrum, T. mentagrophytes, or Epidermophyton floccosum.
A fungal infection of the nail, usually caused by DERMATOPHYTES; YEASTS; or nondermatophyte MOLDS.
A common chronic, noninflammatory and usually symptomless disorder, characterized by the occurrence of multiple macular patches of all sizes and shapes, and varying in pigmentation from fawn-colored to brown. It is seen most frequently in hot, humid, tropical regions, and is caused by Pityrosporon orbiculare. (Dorland, 27th ed)
A 5-nitroimidazole derivative with antiprotozoal property. Although the mechanism of action has not been fully elucidated, it has been suggested that tinidazole is metabolized and yields nitrite anions and metronidazole. Metronidazole's nitro group in turn is reduced via the parasite ferredoxin, thereby generating a series of free nitro radicals including nitro anions. Toxicity is achieved via depletion of sulfhydryl groups and DNA strand breaks with multiple hits having an additive effect and ultimately leading to cell death.
A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of COCHLEAR DISEASES; VESTIBULOCOCHLEAR NERVE DISEASES; INTRACRANIAL HYPERTENSION; CRANIOCEREBRAL TRAUMA; and other conditions.
Any disease or disorder that is caused by the use of tobacco.
Drugs that prevent preterm labor and immature birth by suppressing uterine contractions (TOCOLYSIS). Agents used to delay premature uterine activity include magnesium sulfate, beta-mimetics, oxytocin antagonists, calcium channel inhibitors, and adrenergic beta-receptor agonists. The use of intravenous alcohol as a tocolytic is now obsolete.
An antihypertensive agent with both central and peripheral action; it has some central nervous system depressant effects.
A viral infection caused by any of the arboviruses of the Togaviridae family. It is transmitted by arthropods. Signs and symptoms include fever, headache, nausea, vomiting, rash, confusion, and seizures.
A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE.
A vasodilator that apparently has direct actions on blood vessels and also increases cardiac output. Tolazoline can interact to some degree with histamine, adrenergic, and cholinergic receptors, but the mechanisms of its therapeutic effects are not clear. It is used in treatment of persistent pulmonary hypertension of the newborn.
A short-acting, first-generation sulfonylurea with hypoglycemic activity. Compared to second-generation sulfonylureas, tolbutamide is more likely to cause adverse effects, such as jaundice. This agent is rapidly metabolized by CYPC29.
A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.
A phenothiazine that has been used as a hemostatic, a biological stain, and a dye for wool and silk. Tolonium chloride has also been used as a diagnostic aid for oral and gastric neoplasms and in the identification of the parathyroid gland in thyroid surgery.
An ophthalmoplegic syndrome, affecting all age groups, with characteristics of acute attacks (lasting a few days to a few weeks) of periorbital pain, ipsilateral ocular motor nerve palsies, ptosis, disordered eye movements and blurred vision usually caused by a non-specific inflammatory process in the cavernous sinus and superior orbital fissure. It has an unpredictable course with spontaneous remission occurring in some and recurrence of attacks in others.
A centrally acting muscle relaxant that has been used for the symptomatic treatment of spasticity and muscle spasm. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1211)
An alkaloid that occurs in the extract of leaves of wild tomato plants. It has been found to inhibit the growth of various fungi and bacteria. It is used as a precipitating agent for steroids. (From The Merck Index, 11th ed)
A benign or malignant neoplasm involving the tongue.
Accentuation of the grooves on the dorsal surface of the tongue.
A benign condition affecting the dorsum of the tongue. It is characterized by defective desquamation resulting in elongation of the filiform papillae. The dorsum of the tongue has a furry appearance and is usually stained black.
A pupillary abnormality characterized by a poor pupillary light reaction, reduced accommodation, iris sector palsies, an enhanced pupillary response to near effort that results in a prolonged, ""tonic"" constriction, and slow pupillary redilation. This condition is associated with injury to the postganglionic parasympathetic innervation to the pupil. (From Miller et al., Clinical Neuro-Ophthalmology, 4th ed, pp492-500)
A benign or malignant neoplasm that affects the tonsil.
An abnormality of the morphology of the tooth.
The pathologic wearing away of the tooth substance by brushing, bruxism, clenching, and other mechanical causes. It is differentiated from TOOTH ATTRITION in that this type of wearing away is the result of tooth-to-tooth contact, as in mastication, occurring only on the occlusal, incisal, and proximal surfaces. It differs also from TOOTH EROSION, the progressive loss of the hard substance of a tooth by chemical processes not involving bacterial action. (From Jablonski, Dictionary of Dentistry, 1992, p2)
Overlapping teeth within an alveolar ridge.
A change in tooth color. Causes may be local or systemic and include tobacco use, foods, dental plaques, caries, restorative filling materials, trauma, medications, infections, hereditary diseases, and nutritional deficiencies.
Progressive loss of the hard substance of a tooth by chemical processes that do not involve bacterial action. (Jablonski, Dictionary of Dentistry, 1992, p296)
An abnormality in the direction of a TOOTH ERUPTION.
The movement of teeth into altered positions in relationship to the basal bone of the ALVEOLAR PROCESS and to adjoining and opposing teeth as a result of loss of approximating or opposing teeth, occlusal interferences, habits, inflammatory and dystrophic disease of the attaching and supporting structures of the teeth. (From Boucher's Clinical Dental Terminology, 4th ed)
Resorption of calcified dental tissue, involving demineralization due to reversal of the cation exchange and lacunar resorption by osteoclasts. There are two types: external (as a result of tooth pathology) and internal (apparently initiated by a peculiar inflammatory hyperplasia of the pulp). (From Jablonski, Dictionary of Dentistry, 1992, p676)
A condition in which a tooth is so crowded in its socket that it cannot erupt normally.
An extra tooth, erupted or unerupted, resembling or unlike the other teeth in the group to which it belongs. Its presence may cause malposition of adjacent teeth or prevent their eruption.
A normal developing tooth which has not yet perforated the oral mucosa or one that fails to erupt in the normal sequence or time interval expected for the type of tooth in a given gender, age, or population group.
A painful sensation originating from a tooth.
Anesthetic applied on a specific site of body.
A malignant form of polymorphic ventricular tachycardia that is characterized by HEART RATE between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long QT intervals exceeding 500 milliseconds or BRADYCARDIA. Torsades de pointes may be self-limited or may progress to VENTRICULAR FIBRILLATION.
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
An inhibitor of SERINE ENDOPEPTIDASES. Acts as an alkylating agent and is known to interfere with the translation process.
An inhibitor of Serine Endopeptidases. Acts as alkylating agent and is known to interfere with the translation process.
The total volume of air in the lungs after maximum inhalation.
Tourette syndrome is a neurobehavioral disorder manifest particularly by motor and vocal tics and associated with behavioral abnormalities. Tics are sudden, brief, intermittent, involuntary or semi-voluntary movements (motor tics) or sounds (phonic or vocal tics). They typically consist of simple, coordinated, repetitive movements, gestures, or utterances that mimic fragments of normal behavior. Motor tics may range from simple blinking, nose twitching, and head jerking to more complex throwing, hitting, or making rude gestures. Phonic tics include sniffling, throat clearing, blowing, coughing, echolalia, or coprolalia. Males are affected about 3 times more often than females, and onset usually occurs between 3 and 8 years of age. By age 18 years, more than half of affected individuals are free of tics, but they may persist into adulthood (review by Jankovic, 2001).
Infections with nematodes of the genus TOXASCARIS.
A condition produced by the presence of toxins or other harmful substances in the BLOOD.
A curare alkaloid that is a very potent competitive nicotinic antagonist at the neuromuscular junction.
A parasitic infection caused by Toxocara. Humans are infected by the larvae of Toxocara canis and Toxocara cati from dogs and cats respectively. Most cases remain asymptomatic. The parasites may affect the eye, causing diminished vision, or other major organs, causing hepatomegaly, eosinophilia, wheezing, and coughing.
Preparations of pathogenic organisms or their derivatives made nontoxic and intended for active immunologic prophylaxis. They include deactivated toxins. Anatoxin toxoids are distinct from anatoxins that are TROPANES found in CYANOBACTERIA.
A parasitic disease contracted by the ingestion or fetal transmission of toxoplasma gondii.
Acquired infection of non-human animals by organisms of the genus TOXOPLASMA.
Prenatal protozoal infection with TOXOPLASMA gondii which is associated with injury to the developing fetal nervous system. The severity of this condition is related to the stage of pregnancy during which the infection occurs; first trimester infections are associated with a greater degree of neurologic dysfunction. Clinical features include HYDROCEPHALUS; MICROCEPHALY; deafness; cerebral calcifications; SEIZURES; and psychomotor retardation. Signs of a systemic infection may also be present at birth, including fever, rash, and hepatosplenomegaly. (From Adams et al., Principles of Neurology, 6th ed, p735)
Infection caused by the protozoan parasite TOXOPLASMA in which there is extensive connective tissue proliferation, the retina surrounding the lesions remains normal, and the ocular media remain clear. Chorioretinitis may be associated with all forms of toxoplasmosis, but is usually a late sequel of congenital toxoplasmosis. The severe ocular lesions in infants may lead to blindness.
4-Amino-5-cyano-7-(D-ribofuranosyl)-7H- pyrrolo(2,3-d)pyrimidine. Antibiotic antimetabolite isolated from Streptomyces toyocaensis cultures. It is an analog of adenosine, blocks RNA synthesis and ribosome function, and is used mainly as a tool in biochemistry.
A benign or malignant neoplasm that affects the trachea. Representative examples include tracheal leiomyoma and tracheal carcinoma.
A pathological narrowing of the TRACHEA.
An inflammatory process affecting the wall of the trachea.
Inflammation of the tracheobronchial tree.
A rare and probably congenital condition characterized by great enlargement of the lumen of the trachea and the larger bronchi.
An abnormal connection (fistula) between the esophagus and the trachea.
A chronic infection of the CONJUNCTIVA and CORNEA caused by CHLAMYDIA TRACHOMATIS.
Powdered exudate from Astragalus gummifer and related plants. It forms gelatinous mass in water. Tragacanth is used as suspending agent, excipient or emulsifier in foods, cosmetics and pharmaceuticals. It has also been used as a bulk-forming laxative.
A narcotic analgesic proposed for severe pain. It may be habituating.
A synthetic derivative of the amino acid lysine with antifibrinolytic activity. With strong affinity for the five lysine-binding sites of plasminogen, tranexamic acid competitively inhibits the activation of plasminogen to plasmin, resulting in inhibition of fibrinolysis; at higher concentrations, this agent noncompetitively inhibits plasmin. This agent has a longer half-life, is approximately ten times more potent, and is less toxic than aminocaproic acid, which possesses similar mechanisms of action.
A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the ANTI-ANXIETY AGENTS (minor tranquilizers), ANTIMANIC AGENTS, and the ANTIPSYCHOTIC AGENTS (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes.
Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.
Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.
A neurological disorder presenting in childhood that is characterized by motor and/or phonic tics that occur daily or nearly daily for one to twelve months and are not attributed to an identifiable cause.
A genetic exchange where a piece of one chromosome is transfered to another chromosome.
Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.
A propylamine formed from the cyclization of the side chain of amphetamine. This monoamine oxidase inhibitor is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. (From AMA Drug Evaluations Annual, 1994, p311)
Vascular rupture, and the resulting loss of blood, due to physical injury.
Myositis Ossificans resulting from trauma.
A serotonin uptake inhibitor that is used as an antidepressive agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety. This drug does not aggravate psychotic symptoms in patients with schizophrenia or schizoaffective disorders. (From AMA Drug Evaluations Annual, 1994, p309)
disaccharide occurring mainly in insects, algae, and some mushrooms, yielding glucose when hydrolyzed.
Infections caused by infestation with worms of the class Trematoda.
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
An intermittent fever characterized by intervals of chills, fever, and splenomegaly each of which may last as long as 40 hours. It is caused by BARTONELLA QUINTANA and transmitted by the human louse.
A sexually transmitted infection caused by the Gram-negative spirochete Treponema pallidum. It is manifested as syphilis.
A naturally-occurring acid of retinol. Tretinoin binds to and activates retinoic acid receptors (RARs), thereby inducing changes in gene expression that lead to cell differentiation, decreased cell proliferation, and inhibition of tumorigenesis. This agent also inhibits telomerase, resulting in telomere shortening and eventual apoptosis of some tumor cell types. The oral form of tretinoin has teratogenic and embryotoxic properties.
An adrenergic beta-agonist used as a bronchodilator agent in asthma therapy.
A triglyceride that is used as an antifungal agent.
A glucocorticoid given, as the free alcohol or in esterified form, orally, intramuscularly, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. (From Martindale, The Extra Pharmacopoeia, 30th ed, p739)
An esterified form of TRIAMCINOLONE. It is an anti-inflammatory glucocorticoid used topically in the treatment of various skin disorders. Intralesional, intramuscular, and intra-articular injections are also administered under certain conditions.
A pteridine derivative with potassium-sparing diuretic property. Triamterene blocks the sodium-potassium exchange pump (Na-K-ATPase) in the luminal membrane of principal cells in the late distal tubule, cortical collecting tubule and collecting duct in the kidney. This reversible inhibition of the electrogenic sodium transport decreases the lumen-negative transepithelial potential difference and thus reduces the driving force for K+ movement into the tubular lumen resulting in the inhibition of sodium reabsorption in exchange for K+ and H+.
An aziridinylbenzoquinone-based alkylating agent with potential antineoplastic activity. The alkylating group in triaziquone becomes activated upon reduction of quinone to the hydroquinone form. This eventually results in the alkylation and crosslinking of DNA, thereby inhibiting DNA replication followed by an induction of apoptosis. In addition, reactive oxygen species may form during redox cycling which may contribute to this agent's cytotoxic activity.
A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries.
A parasitic infection caused by larvae of worms of the genus Trichinella. It is transmitted to humans by ingesting raw or undercooked meat from infected animals. Signs and symptoms include abdominal discomfort, nausea, vomiting, fever, diarrhea, headache, coughing, myalgias, arthralgias, and eye swelling.
An organochlorophosphate cholinesterase inhibitor that is used as an insecticide for the control of flies and roaches. It is also used in anthelmintic compositions for animals. (From Merck, 11th ed)
A short-acting, 3-dichloromethyl derivative of hydrochlorothiazide, belonging to the class of thiazide diuretics.
A strong acid used as a protein precipitant in clinical chemistry and also as a caustic for removing warts.
A potent epoxide hydrase and aryl hydrocarbon hydroxylase inhibitor. It enhances the tumor-initiating ability of certain carcinogens.
A highly volatile inhalation anesthetic used mainly in short surgical procedures where light anesthesia with good analgesia is required. It is also used as an industrial solvent. Prolonged exposure to high concentrations of the vapor can lead to cardiotoxicity and neurological impairment.
Antifungal metabolite from several fungi, mainly Trichoderma viride; inhibits protein synthesis by binding to ribosomes; proposed as antifungal and antineoplastic; used as tool in cellular biochemistry.
An infection that is caused by Trichomonas.
A sexually transmitted parasitic infection caused by Trichomonas vaginalis. Symptoms include vaginal discharge, vaginal odor, vaginal itching, and discomfort during intercourse.
Plant-derived ribosome-inactivating protein (RIP) purified from the Chinese medicinal herb tian-hua-fen which is obtained from the root tubers of Trichosanthes kirilowii. It has been used as an abortifacient and in the treatment of trophoblastic tumors. GLQ223 (Compound Q), a highly purified form of trichosanthin, has been proposed as antiviral treatment for AIDS.
Infection by roundworms of the superfamily TRICHOSTRONGYLOIDEA, including the genera TRICHOSTRONGYLUS; OSTERTAGIA; Cooperia, HAEMONCHUS; Nematodirus, Hyostrongylus, and DICTYOCAULUS.
Infestation with nematode worms of the genus TRICHOSTRONGYLUS. Man and animals become infected by swallowing larvae, usually with contaminated food or drink, although the larvae may penetrate human skin.
Trichotillomania (TTM) is a neuropsychiatric disorder characterized by chronic, repetitive, or compulsive hair pulling resulting in noticeable hair loss. The activity causes distress to the individual and often interferes with functioning. Affected individuals may develop physical complications and often have overlapping psychologic disorders, such as Tourette syndrome (GTS; 137580) or obsessive-compulsive disorder (OCD; 164230) (review by Novak et al., 2009).
An infection that is caused by the nematode Trichuris trichiura, a soil-transmitted helminth, which is transmitted via food and/or water contaminated with the eggs of the worm. Symptoms are usually mild and include abdominal pain, diarrhea, fatigue, and possibly anemia secondary to blood loss in diarrhea.
A diphenyl ether derivative used in cosmetics and toilet soaps as an antiseptic. It has some bacteriostatic and fungistatic action.
Backflow of blood from the RIGHT VENTRICLE into the RIGHT ATRIUM due to imperfect closure of the TRICUSPID VALVE.
Abnormal protrusion of one or more of the leaflets of TRICUSPID VALVE into the RIGHT ATRIUM during SYSTOLE. This allows the backflow of blood into right atrium leading to TRICUSPID VALVE INSUFFICIENCY; SYSTOLIC MURMURS. Its most common cause is not primary valve abnormality but rather the dilation of the RIGHT VENTRICLE and the tricuspid annulus.
A narrowing of the orifice of the tricuspid valve of the heart.
A trisaziridine alkylating agent with antineoplastic and carcinogenic properties. Used to induce cancer in experimental animal models, triethylenemelamine ethylates DNA, resulting in inhibition of DNA replication, unscheduled DNA synthesis, chromosomal aberrations, and sister chromatid exchanges. This agent also exhibits reproductive toxicities. (NCI04)
An ethylenediamine derivative used as stabilizer for EPOXY RESINS, as ampholyte for ISOELECTRIC FOCUSING and as chelating agent for copper in HEPATOLENTICULAR DEGENERATION.
Organic compounds composed of tin and three ethyl groups. Affect mitochondrial metabolism and inhibit oxidative phosphorylation by acting directly on the energy conserving processes.
A phenothiazine derivative and a dopamine antagonist with antipsychotic and antiemetic activities. Trifluoperazine exerts its antipsychotic effect by blocking central dopamine receptors, thereby preventing effects such as delusions and hallucinations caused by an excess of dopamine. This agent also functions as a calmodulin inhibitor, thereby leading to elevation of cytosolic calcium.
A fluorinated thymidine analog with potential antineoplastic activity. Trifluridine is incorporated into DNA and inhibits thymidylate synthase, resulting in inhibition of DNA synthesis, inhibition of protein synthesis, and apoptosis. This agent also exhibits antiviral activity. (NCI04)
A butyrophenone with general properties similar to those of HALOPERIDOL. It is used in the treatment of PSYCHOSES including MANIA and SCHIZOPHRENIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p621)
A phenothiazine used as an antipsychotic agent and as an antiemetic.
A neuropathic disorder characterized by episodes of intense pain in the face, originating from the trigeminal nerve. One, two, or all three branches of the nerve may be affected.
One of the centrally acting MUSCARINIC ANTAGONISTS used for treatment of PARKINSONIAN DISORDERS and drug-induced extrapyramidal movement disorders and as an antispasmodic.
A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.
A metabolite of THYROXINE, formed by the peripheral enzymatic monodeiodination of T4 at the 5 position of the inner ring of the iodothyronine nucleus.
A combination of congenital heart defects consisting of three key features including ATRIAL SEPTAL DEFECTS; PULMONARY STENOSIS; and RIGHT VENTRICULAR HYPERTROPHY.
Proposed spasmolytic with possible local anesthetic action used in gastrointestinal disorders.
Acetanilide derivative used as a local anesthetic.
Cholinesterase reactivator used as an antidote in alkyl phosphate poisoning.
A beta-adrenergic antagonist effective for both beta-1 and beta-2 receptors. It is used as an antiarrhythmic, antihypertensive, and antiglaucoma agent.
A phenothiazine derivative that is used as an antipruritic.
A vasodilator used in angina of effort or ischemic heart disease.
A dione-type anticonvulsant with antiepileptic activity. Trimethadione reduces T-type calcium currents in thalamic neurons, thereby stabilizing neuronal membranes, raising the threshold for repetitive activities in the thalamus and inhibiting corticothalamic transmission. This decreases the abnormal thalamocortical rhythmicity, which is thought to underlie the paroxysmal three-cycle-per-second spike-and-wave pattern seen with absence (petit mal) seizures.
A nicotinic antagonist that has been used as a ganglionic blocker in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.
A drug combination with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.
Organic compounds composed of tin and three methyl groups. Affect mitochondrial metabolism and inhibit oxidative phosphorylation by acting directly on the energy conserving processes.
Tricyclic antidepressant similar to IMIPRAMINE, but with more antihistaminic and sedative properties.
(Z)-9-Octadecenoic acid 1,2,3-propanetriyl ester.
Pigmenting photosensitizing agent obtained from several plants, mainly Psoralea corylifolia. It is administered either topically or orally in conjunction with ultraviolet light in the treatment of vitiligo.
A histamine H1 antagonist with low sedative action but frequent gastrointestinal irritation. It is used to treat ASTHMA; HAY FEVER; URTICARIA; and RHINITIS; and also in veterinary applications. Tripelennamine is administered by various routes, including topically.
Histamine H1 antagonist used in allergic rhinitis; ASTHMA; and URTICARIA. It is a component of COUGH and COLD medicines. It may cause drowsiness.
Lack of ability to open the mouth fully due to decreased range of motion of the muscles of mastication. It may be a symptom of tetanus.
A chromosomal abnormality consisting of the presence of one chromosome in addition to the normal diploid number.
Infestation with mites of the genus Trombicula, whose larvae carry the rickettsial agent of scrub typhus.
An organic amine proton acceptor. It is used in the synthesis of surface-active agents and pharmaceuticals; as an emulsifying agent for cosmetic creams and lotions, mineral oil and paraffin wax emulsions, as a biological buffer, and used as an alkalizer. (From Merck, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p1424)
A gestational or non-gestational neoplasm composed of neoplastic trophoblastic cells [NCIT:C3422].
A synthetic muscarinic antagonist with actions similar to atropine and with an anticholinergic property. Upon ocular administration, tropicamide binds to and blocks the muscarinic receptors in the sphincter and ciliary muscle in the eye. This inhibits the responses from cholinergic stimulation, producing dilation of the pupil and paralysis of the ciliary muscle. Tropicamide is a diagnostic agent and is used to produce short-duration mydriasis and cycloplegia.
Agents destructive to the protozoal organisms belonging to the suborder TRYPANOSOMATINA.
Infection with protozoa of the genus TRYPANOSOMA.
A disease endemic among people and animals in Central Africa. It is caused by various species of trypanosomes, particularly T. gambiense and T. rhodesiense. Its second host is the TSETSE FLY. Involvement of the central nervous system produces ""African sleeping sickness."" Nagana is a rapidly fatal trypanosomiasis of horses and other animals.
Infection in cattle caused by various species of trypanosomes.
Trypanosomiasis caused by infection by Trypanosoma brucei gambiense.
An infection with Trypanosoma brucei rhodesiense.
A parasitic infection caused by Trypanosoma cruzi. It is transmitted by insect bites. It is characterized by an acute and chronic phase; in the acute phase patients may have fever, malaise, and swelling at the site of the insect bite. In the chronic phase patients develop hepatosplenomegaly, lymphadenopathy, cardiomyopathy and arrhythmias.
An arsenic compound with activity against Spirochaetes bacteria. Tryparsamide is used in the treatment of syphilis and African sleeping sickness.
A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4.
A low-molecular-weight protein (minimum molecular weight 8000) which has the ability to inhibit trypsin as well as chymotrypsin at independent binding sites. It is characterized by a high cystine content and the absence of glycine.
A high-molecular-weight protein (approximately 22,500) containing 198 amino acid residues. It is a strong inhibitor of trypsin and human plasmin.
Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds.
An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.
Blockage of the normal flow of the contents in the fallopian tube.
An antibiotic and adenosine analog isolated from the bacterium Streptomyces tubercidicus with potential antineoplastic activity. Tubercidin is incorporated into DNA and inhibits polymerases, thereby inhibiting DNA replication and RNA and protein synthesis. This agent also exhibits antifungal and antiviral activities. (NCI04)
A tumor-like mass resulting from the enlargement of a tuberculous lesion.
A chronic, recurrent infection caused by the bacterium Mycobacterium tuberculosis. Tuberculosis (TB) may affect almost any tissue or organ of the body with the lungs being the most common site of infection. The clinical stages of TB are primary or initial infection, latent or dormant infection, and recrudescent or adult-type TB. Ninety to 95% of primary TB infections may go unrecognized. Histopathologically, tissue lesions consist of granulomas which usually undergo central caseation necrosis. Local symptoms of TB vary according to the part affected; acute symptoms include hectic fever, sweats, and emaciation; serious complications include granulomatous erosion of pulmonary bronchi associated with hemoptysis. If untreated, progressive TB may be associated with a high degree of mortality. This infection is frequently observed in immunocompromised individuals with AIDS or a history of illicit IV drug use.
Vaccines or candidate vaccines used to prevent or treat TUBERCULOSIS.
A variety of TUBERCULOSIS affecting various birds, including chickens and ducks. It is caused by MYCOBACTERIUM AVIUM and characterized by tubercles consisting principally of epithelioid cells.
An infection of cattle caused by MYCOBACTERIUM BOVIS. It is transmissible to man and other animals.
Pathological conditions of the CARDIOVASCULAR SYSTEM caused by infection of MYCOBACTERIUM TUBERCULOSIS. Tuberculosis involvement may include the HEART; the BLOOD VESSELS; or the PERICARDIUM.
Tuberculosis of the skin. It includes scrofuloderma and tuberculid, but not LUPUS VULGARIS.
Infection of the ENDOCRINE GLANDS with species of MYCOBACTERIUM, most often MYCOBACTERIUM TUBERCULOSIS.
MYCOBACTERIUM infections of the female reproductive tract (GENITALIA, FEMALE).
TUBERCULOSIS that involves any region of the GASTROINTESTINAL TRACT, mostly in the distal ILEUM and the CECUM. In most cases, MYCOBACTERIUM TUBERCULOSIS is the pathogen. Clinical features include ABDOMINAL PAIN; FEVER; and palpable mass in the ileocecal area.
Infection of the LIVER with species of MYCOBACTERIUM, most often MYCOBACTERIUM TUBERCULOSIS. It is characterized by localized small tuberculous miliary lesions or tumor-like mass (TUBERCULOMA), and abnormalities in liver function tests.
Extrapulmonary tuberculosis involving the larynx. Signs and symptoms include hoarseness, cough, and odynophagia. The condition is rare.
Infection of the lymph nodes by tuberculosis. Tuberculous infection of the cervical lymph nodes is scrofula.
MYCOBACTERIUM infections of the male reproductive tract (GENITALIA, MALE).
A bacterial infection of the membranes covering the brain and the spinal cord caused by Mycobacterium tuberculosis.
An acute form of TUBERCULOSIS in which minute tubercles are formed in a number of organs of the body due to dissemination of the bacilli through the blood stream.
Tuberculous infection of the eye, primarily the iris, ciliary body, and choroid.
Tuberculosis of the mouth, tongue, and salivary glands.
A form of PERITONITIS seen in patients with TUBERCULOSIS, characterized by lesion either as a miliary form or as a pelvic mass on the peritoneal surfaces. Most patients have ASCITES, abdominal swelling, ABDOMINAL PAIN, and other systemic symptoms such as FEVER; WEIGHT LOSS; and ANEMIA.
Inflammation of the pleura secondary to an infection with Mycobacterium tuberculosis.
A bacterial infection that affects the lungs and is caused by Mycobacterium tuberculosis. Most patients with tuberculosis do not have symptoms (latent tuberculosis) and are not contagious. When signs and symptoms occur (active tuberculosis), patients become contagious. The signs and symptoms include chronic cough with blood-tinged sputum, night sweats, fever, fatigue, and weight loss.
Infection of the KIDNEY with species of MYCOBACTERIUM.
Osteitis or caries of the vertebrae, usually occurring as a complication of tuberculosis of the lungs.
Infection of the spleen with species of MYCOBACTERIUM.
A general term for MYCOBACTERIUM infections of any part of the UROGENITAL SYSTEM in either the male or the female.
Scarring of the lung parenchyma caused by pulmonary tuberculosis.
Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, confetti skin lesions, facial angiofibromas, shagreen patches, fibrous cephalic plaques, ungual fibromas); brain (subependymal nodules, cortical dysplasias, and subependymal giant cell astrocytomas [SEGAs], seizures, intellectual disability / developmental delay, psychiatric illness); kidney (angiomyolipomas, cysts, renal cell carcinomas); heart (rhabdomyomas, arrhythmias); and lungs (lymphangioleiomyomatosis [LAM], multifocal micronodular pneumonocyte hyperplasia). Central nervous system tumors are the leading cause of morbidity and mortality; renal disease is the second leading cause of early death.
An abscess involving the distal fallopian tube and ovary. It is caused by pelvic inflammatory disease or other infections.
A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.
A form of inflammation of the kidney affecting the interstitium of the kidneys surrounding the tubules.
A plague-like disease of rodents, transmissible to man. It is caused by FRANCISELLA TULARENSIS and is characterized by fever, chills, headache, backache, and weakness.
A condition of metabolic abnormalities that result from a spontaneous or therapy-related cytolysis of tumor cells. Tumor lysis syndrome typically occurs in aggressive, rapidly proliferating lymphoproliferative disorders. Burkitt lymphoma and T cell acute lymphoblastic leukemia are commonly associated with this syndrome. Metabolic abnormalities include hyperuricemia, lactic acidosis, hyperkalemia, hyperphosphatemia and hypocalcemia and may result in renal failure, multiple organ failure, and death.
Infections produced by oncogenic viruses. The infections caused by DNA viruses are less numerous but more diverse than those caused by the RNA oncogenic viruses.
Turner syndrome is a chromosomal condition that affects development in females. The most common feature of Turner syndrome is short stature, which becomes evident by about age 5. An early loss of ovarian function (ovarian hypofunction or premature ovarian failure) is also very common. The ovaries develop normally at first, but egg cells (oocytes) usually die prematurely and most ovarian tissue degenerates before birth. Many affected girls do not undergo puberty unless they receive hormone therapy, and most are unable to conceive (infertile). A small percentage of females with Turner syndrome retain normal ovarian function through young adulthood.About 30 percent of females with Turner syndrome have extra folds of skin on the neck (webbed neck), a low hairline at the back of the neck, puffiness or swelling (lymphedema) of the hands and feet, skeletal abnormalities, or kidney problems. One third to one half of individuals with Turner syndrome are born with a heart defect, such as a narrowing of the large artery leaving the heart (coarctation of the aorta) or abnormalities of the valve that connects the aorta with the heart (the aortic valve). Complications associated with these heart defects can be life-threatening.Most girls and women with Turner syndrome have normal intelligence. Developmental delays, nonverbal learning disabilities, and behavioral problems are possible, although these characteristics vary among affected individuals.
A monoamniotic twin gestation in which the twins share one or more organs.
A heterotrimeric fibrillar protein complex comprised of two collagen alpha-1(I) chains and one collagen alpha-2(I) chains. Type I collagen is the most abundant fibrillar collagen in humans and is present in scar tissue, tendons, ligaments, bone, dermis, dentin, and organ capsules.
A bacterial infectious disorder contracted by consumption of food or drink contaminated with Salmonella typhi. This disorder is common in developing countries and can be treated with antibiotics.
A bacterial vaccine used to prevent typhoid fever, which is caused by Salmonella typhi bacteria.
Vaccines used to prevent TYPHOID FEVER and/or PARATYPHOID FEVER which are caused by various species of SALMONELLA. Attenuated, subunit, and inactivated forms of the vaccines exist.
group of acute, arthropod borne infections caused by rickettsiae; includes epidemic (classic or louse-borne) typhus, its recrudescent form, and murine (endemic or flea-borne) typhus; all are characterized by severe headache, chills, high fever, stupor, and rash.
A bacterial infection caused by Rickettsia typhi or Rickettsia felis. It is transmitted to humans from infected rat fleas. Symptoms include fever, headache, joint and muscle pain, and weakness.
A gram-negative bacterial infection caused by Rickettsia prowazekii. It is spread by lice infected with the bacteria. Signs and symptoms include sudden headache, generalized muscle pain, malaise, and macular skin lesions. The infection may affect the central nervous system causing encephalitis.
An indirect sympathomimetic that occurs naturally in cheese and other foods. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and MONOAMINE OXIDASE to prolong the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals and may be a neurotransmitter in some invertebrate nervous systems.
An antibiotic mixture produced by Bacillus brevis which may be separated into three components, tyrocidines A, B, and C. It is the major constituent (40-60 per cent) of tyrothricin, gramicidin accounting for the remaining 10-20 per cent active material. It is a topical antimicrobial agent, that is very toxic parenterally.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A lipid-soluble benzoquinone which is involved in ELECTRON TRANSPORT in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals.
A circumscribed inflammatory and often suppurating lesion on the skin or an internal mucous surface resulting in necrosis of tissue.
A long-acting form of crystalline insulin often used in combination with a short-acting insulin in the treatment of diabetes mellitus. Administered once daily, this type of insulin may be derived from porcine, bovine, or recombinant sources. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats; it has anabolic effects on many types of tissues. (NCI04)
An inability to purposefully respond to stimuli.
Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those IONOPHORES that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes.
A natural or synthetic fungistatic fatty acid, antifungal Undecylenic Acid is used topically as a zinc salt in various creams against fungal infections, eczemas, ringworm, and other cutaneous conditions. The zinc provides an astringent action, reducing rawness and irritation.
A mental disorder characterized by inattention, easy distraction, careless mistakes and avoidance of tasks that require sustained mental focus. These behaviors can lead to maladaptive consequences in the affected individual's life.
The state of not being engaged in a gainful occupation.
A mood disorder having a clinical course involving one or more episodes of serious psychological depression that last two or more weeks each, do not have intervening episodes of mania or hypomania, and are characterized by a loss of interest or pleasure in almost all activities and by some or all of disturbances of appetite, sleep, or psychomotor functioning, a decrease in energy, difficulties in thinking or making decisions, loss of self-esteem or feelings of guilt, and suicidal thoughts or attempts.
A chelating agent used as an antidote to heavy metal poisoning.
A pregnancy that was not desired or was timed incorrectly at the time that the conception occurred.
All noxious and unintended responses to a medicinal product related to any dose should be considered adverse drug reactions (from US FDA 'Guideline for Industry, Clinical Safety Data Management: Definitions and Standards for Expedited Reporting').
Any anatomic abnormality of the arm located between the elbow and the wrist.
Red discoloration of the skin caused by infectious agents, inflammation, drug hypersensitivity, or underlying disease.
Neuropathy, the cause of which is not known.
Any mental disorder that occurs secondary to organic brain damage, and that is not associated with psychosis.
An organic mental disorder that is temporary in nature.
Lability of an individual's outward presentation, which is characterized by unpredictable social behavior or uneven mood.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Bleeding originating from the upper gastrointestinal tract (oral cavity, pharynx, esophagus, and stomach).
An infectious process affecting the upper respiratory tract (nose, paranasal sinuses, pharynx, larynx, or trachea). Symptoms include congestion, sneezing, coughing, fever, and sore throat.
A cyst located along the allantois canal.
One of four nucleotide bases in the nucleic acid RNA.
An alkylating derivative of the pyrimidine nucleobase uracil that is bound to nitrogen mustard, with antineoplastic activity. Uramustine alkylates and damages DNA by binding to the guanine and cytosine moieties of DNA. This leads to cross-linking of DNA, which inhibits DNA synthesis and promotes cell death in rapidly metabolizing cells, such as cancer cells.
A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.
A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of RENAL INSUFFICIENCY. Most uremic toxins are end products of protein or nitrogen CATABOLISM, such as UREA or CREATININE. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms.
Pathological processes involving the URETERS.
A benign or malignant neoplasm that affects the ureter.
Blockage in any part of the URETER causing obstruction of urine flow from the kidney to the URINARY BLADDER. The obstruction may be congenital, acquired, unilateral, bilateral, complete, partial, acute, or chronic. Depending on the degree and duration of the obstruction, clinical features vary greatly such as HYDRONEPHROSIS and obstructive nephropathy.
An acute or chronic inflammatory process affecting the ureter.
A colorless and odorless, crystalline compound that emits toxic fumes of nitrogen oxides when heated to decomposition. Urethan is mainly used in the production of amino resins, but is also used in the manufacture of pesticides, fumigants, cosmetics and pharmaceuticals. Exposure to urethan can affect the central nervous system, liver and can cause bone marrow suppression. Urethan is reasonably anticipated to be a human carcinogen. (NCI05)
A non-neoplastic or neoplastic disorder that affects the urethra.
An abnormal communication between the urethra and another organ or anatomic site.
A benign or malignant neoplasm that affects the urethra. Urethra carcinoma is a representative example.
Blockage of the normal flow of urine in the urethra.
A laboratory test result indicating abnormally high concentration of uric acid in the blood.
A pharmacological agent that increases the urinary excretion of uric acid by inhibiting reabsorption in the renal tubule.
A nucleoside consisting of uracil and D-ribose and a component of RNA. Uridine has been studied as a rescue agent to reduce the toxicities associated with 5-fluorouracil (5-FU), thereby allowing the administration of higher doses of 5-FU in chemotherapy regimens. (NCI04)
An abnormal communication between any part of the urinary system and another organ or cavity.
Involuntary loss of URINE, such as leaking of urine. It is a symptom of various underlying pathological processes. Major types of incontinence include URINARY URGE INCONTINENCE and URINARY STRESS INCONTINENCE.
In voluntary urine leakage synchronous with exertion, or actions such as sneezing, or coughing.
A bacterial infectious process affecting any part of the urinary tract, most commonly the bladder and the urethra. Symptoms include urinary urgency and frequency, burning sensation during urination, lower abdominal discomfort, and cloudy urine.
An abnormal connection between the urinary system and the genitals in a female; the most common examples are a urovaginal fistula, and a rectovaginal fistula.
Abnormalities in the process of URINE voiding, including bladder control, frequency of URINATION, as well as the volume and composition of URINE.
An abnormality of the genitourinary system that is present at birth or detected in the neonatal period.
A tumor (abnormal growth of tissue) of the genitourinary system.
A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.
Disorders of any part of the urologic system.
A benign or malignant, primary or metastatic neoplasm involving the urinary system. --2003
A synthetically-derived form of ursodiol, a bile acid produced by the liver and secreted and stored in the gallbladder. Also produced by the Chinese black bear liver, ursodiol has been used in the treatment of liver disease for centuries. This agent dissolves or prevents cholesterol gallstones by blocking hepatic cholesterol production and decreasing bile cholesterol. Ursodiol also reduces the absorption of cholesterol from the intestinal tract.
A raised, erythematous papule or cutaneous plaque, usually representing short-lived dermal edema
The most common form of cutaneous mastocytosis (MASTOCYTOSIS, CUTANEOUS) that occurs primarily in children. It is characterized by the multiple small reddish-brown pigmented pruritic macules and papules.
A non-neoplastic or neoplastic disorder that affects the uterine corpus or the cervix. Representative examples of non-neoplastic disorders include endometritis and cervicitis. Representative examples of neoplastic disorders include endometrial carcinoma, carcinosarcoma, and cervical carcinoma.
A benign smooth muscle neoplasm arising from the body of the uterus. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
Bleeding from blood vessels in the UTERUS, sometimes manifested as vaginal bleeding.
Failure of the UTERUS to contract with normal strength, duration, and intervals during childbirth (LABOR, OBSTETRIC). It is also called uterine atony.
A benign or malignant neoplasm that affects the uterine corpus or the cervix. Representative examples of benign neoplasms include leiomyoma, adenomyoma, and endocervical polyp. Representative examples of malignant neoplasms include endometrial carcinoma, carcinosarcoma, and cervical carcinoma.
A hole or break through the wall of the UTERUS, usually made by the placement of an instrument or INTRAUTERINE DEVICES.
Downward displacement of the UTERUS. It is classified in various degrees: in the first degree the UTERINE CERVIX is within the vaginal orifice; in the second degree the cervix is outside the orifice; in the third degree the entire uterus is outside the orifice.
A complete separation or tear in the wall of the UTERUS with or without expulsion of the FETUS. It may be due to injuries, multiple pregnancies, large fetus, previous scarring, or obstruction.
A non-neoplastic or neoplastic disorder that affects the uvea. Representative examples include uveitis, chorioretinitis, and uveal melanoma.
A neoplasm that affects the uvea. Uveal melanoma is a representative example.
An inflammatory process affecting a part of or the entire uvea. Causes include inflammatory agents (e.g., herpes simplex, herpes zoster, leptospirosis) and systemic diseases (e.g., inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, ankylosing spondylitis). Patients present with pain and redness in the eye, light sensitivity, and blurred and decreased vision.
Inflammation of the anterior uvea comprising the iris, angle structures, and the ciliary body. Manifestations of this disorder include ciliary injection, exudation into the anterior chamber, iris changes, and adhesions between the iris and lens (posterior synechiae). Intraocular pressure may be increased or reduced.
Inflammation of the pars plana, ciliary body, and adjacent structures.
An inflammatory process that affects the choroid.
Intraocular infection caused mainly by pus-producing bacteria and rarely by fungi. The infection may be caused by an injury or surgical wound (exogenous) or by endogenous septic emboli in such diseases as bacterial endocarditis or meningococcemia.
A syndrome characterized by bilateral granulomatous UVEITIS with IRITIS and secondary GLAUCOMA, premature ALOPECIA, symmetrical VITILIGO, poliosis circumscripta (a strand of depigmented hair), HEARING DISORDERS, and meningeal signs (neck stiffness and headache). Examination of the cerebrospinal fluid reveals a pattern consistent with MENINGITIS, ASEPTIC. (Adams et al., Principles of Neurology, 6th ed, p748; Surv Ophthalmol 1995 Jan;39(4):265-292)
A manifestation of sarcoidosis marked by chronic inflammation of the parotid gland and the uvea.
Preparations containing substances with antigenic properties administered to activate the immune system, thereby inducing an immune response.
Any vaccine created by reducing the virulence of the infectious agent but still keeping the agent viable (live). In the production of an attenuated vaccine, the infectious agent is altered so that it becomes harmless or less virulent. This is in contrast to those vaccines produced by killing the pathogen (inactivated vaccine).
A preparation of killed microorganisms that is intended to prevent or treat an infectious disease by inducing active immunity to the causative microorganism.
Small synthetic peptides that mimic surface antigens of pathogens and are immunogenic, or vaccines manufactured with the aid of recombinant DNA techniques. The latter vaccines may also be whole viruses whose nucleic acids have been modified.
The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine.
A primary or metastatic malignant neoplasm involving the vagina. Representative examples include carcinomas and sarcomas.
A non-neoplastic or neoplastic disorder that affects the vagina. Representative examples include vaginal infection, vaginal polyp, and vaginal squamous cell carcinoma.
An abnormal anatomical passage that connects the VAGINA to other organs, such as the bladder (VESICOVAGINAL FISTULA) or the rectum (RECTOVAGINAL FISTULA).
A benign or malignant neoplasm affecting the vagina. Representative examples of benign neoplasms include squamous papilloma and melanocytic nevus. Representative examples of malignant neoplasms include carcinoma, melanoma, and sarcoma.
Involuntary spasm of the outer muscles of the vagina during penetration that results from a psychological cause.
A non-infectious or infectious inflammatory process affecting the vagina.
A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.
Structural abnormality in which a valve fails to close properly. This includes abnormalities of the valve leaflets as well as so-called functional insufficiency due to other abnormalities such as annular dilatation in the presence of morphologically normal leaflets.
A condition characterized by the dilated tortuous veins of the SPERMATIC CORD with a marked left-sided predominance. Adverse effect on male fertility occurs when varicocele leads to an increased scrotal (and testicular) temperature and reduced testicular volume.
Skin breakdown or ulceration in the drainage area of a VARICOSE VEIN, usually in the leg.
A vascular abnormality characterized by the presence of enlarged and tortuous veins, particularly in the legs.
Inflammation of enlarged and tortuous veins in the hip, thigh, leg and/or foot.
A disorder of the vasculature of the cornea.
A non-neoplastic or neoplastic disorder affecting the arteries, veins, or lymphatic vessels. Examples include vasculitis, thrombophlebitis, arteriosclerosis, lymphedema, hemangioma, and angiosarcoma.
Headache caused by abnormal functioning of the vascular system.
An inflammatory process involving the wall of the vessels (large, medium, or small-sized vessels). The inflammatory process may cause necrosis or formation of granulomas in the vascular wall. It may be the result of an autoimmune disorder, infection, or malignancy. Representative examples include polyarteritis nodosa, temporal arteritis, Wegener granulomatosis, Kawasaki disease, Takayasu arteritis, and Henoch-Schonlein purpura.
Any substance used in the treatment of hypotension. A vasopressor agent increases reduced blood pressure.
Drugs designed to treat inflammation of the nasal passages, generally the result of an infection (more often than not the common cold) or an allergy related condition, e.g., hay fever. The inflammation involves swelling of the mucous membrane that lines the nasal passages and results in inordinate mucus production. The primary class of nasal decongestants are vasoconstrictor agents. (From PharmAssist, The Family Guide to Health and Medicine, 1993)
Any agent that causes widening of blood vessels as a result of smooth muscle relaxation.
Antidiuretic hormones released by the NEUROHYPOPHYSIS of all vertebrates (structure varies with species) to regulate water balance and OSMOLARITY. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a CYSTINE. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the KIDNEY COLLECTING DUCTS to increase water reabsorption, increase blood volume and blood pressure.
An autonomic reflex response to emotional or orthostatic stress, which is characterized by paradoxical hypotension and bradycardia.
Monoquaternary homolog of PANCURONIUM. A non-depolarizing neuromuscular blocking agent with shorter duration of action than pancuronium. Its lack of significant cardiovascular effects and lack of dependence on good kidney function for elimination as well as its short duration of action and easy reversibility provide advantages over, or alternatives to, other established neuromuscular blocking agents.
Failure of the SOFT PALATE to reach the posterior pharyngeal wall to close the opening between the oral and nasal cavities. Incomplete velopharyngeal closure is primarily related to surgeries (ADENOIDECTOMY; CLEFT PALATE) or an incompetent PALATOPHARYNGEAL SPHINCTER. It is characterized by hypernasal speech.
Tumors most commonly seen on or near the genitalia. They are venereal, most likely transmitted through transplantation of cells by contact. Metastases have been reported. Spontaneous regression may occur.
Tissue congestion due to the obstruction of venous blood flow return.
A condition in which there is inadequate blood flow through a vein.
Formation of a blood clot (thrombus) inside a vein, causing the obstruction of blood flow.
The volume of blood in a ventricle after DIASTOLE.
A disorder characterized by an electrocardiographic finding of a rapid grossly irregular ventricular rhythm with marked variability in QRS cycle length, morphology, and amplitude. The rate is typically greater than 300 bpm. (CDISC)
Occlusion of the outflow tract in either the LEFT VENTRICLE or the RIGHT VENTRICLE of the heart. This may result from CONGENITAL HEART DEFECTS, predisposing heart diseases, complications of surgery, or HEART NEOPLASMS.
A disorder characterized by an electrocardiographic finding of three or more consecutive complexes of ventricular origin with a rate greater than a certain threshold (100 or 120 beats per minute are commonly used). The QRS complexes are wide and have an abnormal morphology. (CDISC)
Toxic substances isolated from various strains of Streptomyces. They are 20-membered macrolides that inhibit oxidative phosphorylation and mitochondrial ATPases. Venturicidins A and B are glycosides. Used mainly as tools in the study of mitochondrial function.
A calcium channel blocker that is a class IV anti-arrhythmia agent.
A benzoate-cevane found in VERATRUM and Schoenocaulon. It activates SODIUM CHANNELS to stay open longer than normal.
A voltage-gated sodium channel activator
Alkaloids with powerful hypotensive effects isolated from American or European Hellebore (Veratrum viride Ait. Liliaceae and Veratrum album L. Liliaceae). They increase cholinergic and decrease adrenergic tone with appropriate side effects and at higher doses depress respiration and produce cardiac arrhythmias; only the ester alkaloids have been used as hypotensive agents in specific instances. They have been generally replaced by drugs with fewer adverse effects.
A wart in the plantar surface of the foot. It is caused by human papillomavirus.
Localized or diffuse reduction in blood flow through the vertebrobasilar arterial system, which supplies the BRAIN STEM; CEREBELLUM; OCCIPITAL LOBE; medial TEMPORAL LOBE; and THALAMUS. Characteristic clinical features include SYNCOPE; lightheadedness; visual disturbances; and VERTIGO. BRAIN STEM INFARCTIONS or other BRAIN INFARCTION may be associated.
A feeling of movement, a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). Vertigo is medically distinct from dizziness, lightheadedness, and unsteadiness.
Abnormal (retrograde) movement of urine from the bladder into ureters or kidneys related to inadequacy of the valvular mechanism at the ureterovesicular junction or other causes.
An abnormal anatomical passage between the URINARY BLADDER and the VAGINA.
A calicivirus infection of swine characterized by hydropic degeneration of the oral and cutaneous epithelia.
Pathological processes of the VESTIBULAR LABYRINTH which contains part of the balancing apparatus. Patients with vestibular diseases show instability and are at risk of frequent falls.
Infections with bacteria of the genus VIBRIO.
A nucleoside analog with activity against herpes simplex virus and varicella zoster virus. Vidarabine is converted to a monophosphate by viral thymidine kinase and is further modified to a triphosphate form by host enzymes. Vidarabine triphosphate directly inhibits DNA polymerase and also acts as a chain terminator in DNA replication.
A morpholine derivative used as an antidepressant. It is similar in action to IMIPRAMINE.
A natural alkaloid isolated from the plant Vinca rosea Linn. Vinblastine binds to tubulin and inhibits microtubule formation, resulting in disruption of mitotic spindle assembly and arrest of tumor cells in the M phase of the cell cycle. This agent may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis. (NCI04)
The sulfate salt of vinblastine, a natural alkaloid isolated from the plant Catharanthus roseus (Madagascar periwinkle) with antineoplastic properties. Vinblastine disrupts microtubule formation and function during mitosis and interferes with glutamic acid metabolism. (NCI04)
A group of indole-indoline dimers which are ALKALOIDS obtained from the VINCA genus of plants. They inhibit polymerization of TUBULIN into MICROTUBULES thus blocking spindle formation and arresting cells in METAPHASE. They are some of the most useful ANTINEOPLASTIC AGENTS.
A major alkaloid of Vinca minor L., Apocynaceae. It has been used therapeutically as a vasodilator and antihypertensive agent, particularly in cerebrovascular disorders.
A natural alkaloid isolated from the plant Vinca rosea Linn. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis. (NCI04)
The sulfate salt of a natural alkaloid isolated from the plant Catharanthus roseus (Vinca rosea L.) with antimitotic and antineoplastic activities. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca(2+)-activated ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis.
A synthetic derivative of vinblastine, a naturally occurring vinca alkaloid. Vindesine binds to and stabilizes tubulin, thereby interrupting tubulin polymerization and preventing the formation of the mitotic spindle and cell division; treated cells are unable to undergo mitosis and are arrested in metaphase. This agent also disrupts macromolecular synthesis. (NCI04)
The sulfate salt form of Vindesine. Vindesine binds to and stabilizes tubulin, thereby interrupting tubulin polymerization and preventing the formation of the mitotic spindle and cell division; treated cells are unable to undergo mitosis and are arrested in metaphase. This agent also disrupts macromolecular synthesis. (NCI)
An act of aggression between individuals.
An acute or chronic inflammation of the liver parenchyma caused by viruses. Representative examples include hepatitis A, B, and C, cytomegalovirus hepatitis, and herpes simplex hepatitis.
Any vaccine raised against any virus or viral derivative that causes hepatitis.
Any vaccine preparation composed of a live, attenuated, inactivated, killed or recombinant virus. Administration of a viral vaccine is to provide prophylaxis against viral disease or used as a vehicle to treat cancers.
A laboratory test result indicating the presence of a virus in the blood.
Development of male secondary SEX CHARACTERISTICS in the FEMALE. It is due to the effects of androgenic metabolites of precursors from endogenous or exogenous sources, such as ADRENAL GLANDS or therapeutic drugs.
A general term for diseases caused by viruses.
Familial visceral myopathy is a rare inherited form of myopathic pseudoobstruction, characterized by impaired function of enteric smooth muscle cells resulting in abnormal intestinal mobility, severe abdominal pain, malnutrition, and even death (Lehtonen et al., 2012). Visceral myopathy represents a phenotypic spectrum of disease characterized by inter- and intrafamilial variability, in which the most severely affected patients exhibit prenatal bladder enlargement, intestinal malrotation, neonatal functional gastrointestinal obstruction, and chronic dependence on total parenteral nutrition (TPN) and urinary catheterization (summary by Wangler et al., 2014). Another form of visceral myopathy with functional gastrointestinal obstruction is associated with external ophthalmoplegia (277320). Functional gastrointestinal obstruction also occurs in association with other abnormalities, such as 'prune belly' syndrome (100100) and Barrett esophagus (Mungan syndrome; 611376). Chronic intestinal pseudoobstruction can also be neuropathic in origin (see 609629).
Abnormal increased size of the viscera of the abdomen.
The prolapse or downward displacement of the VISCERA.
Visual sensation derived from sensory stimulation by objects or shadows inside the eye itself, such as floating vitreous fibers, tissues, or blood.
Reduced ability to perceive visual stimuli.
Adverse effects experienced with normal viewing, which may include eye strain, blurred vision, and diplopia.
Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of CAROTENOIDS found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products.
A nutritional condition produced by a deficiency of VITAMIN A in the diet, characterized by NIGHT BLINDNESS and other ocular manifestations such as dryness of the conjunctiva and later of the cornea (XEROPHTHALMIA). Vitamin A deficiency is a very common problem worldwide, particularly in developing countries as a consequence of famine or shortages of vitamin A-rich foods. In the United States it is found among the urban poor, the elderly, alcoholics, and patients with malabsorption. (From Cecil Textbook of Medicine, 19th ed, p1179)
A cobalt-containing coordination compound generated by intestinal microbes, and a natural water-soluble vitamin of the B-complex family that must combine with Intrinsic Factor for absorption by the intestine. Cyanocobalamin is necessary for hematopoiesis, neural metabolism, DNA and RNA production, and carbohydrate, fat, and protein metabolism. B12 improves iron functions in the metabolic cycle and assists folic acid in choline synthesis. B12 metabolism is interconnected with that of folic acid. Vitamin B12 deficiency causes pernicious anemia, megaloblastic anemia, and neurologic lesions.
A nutritional condition produced by a deficiency of VITAMIN B 12 in the diet, characterized by megaloblastic anemia. Since vitamin B 12 is not present in plants, humans have obtained their supply from animal products, from multivitamin supplements in the form of pills, and as additives to food preparations. A wide variety of neuropsychiatric abnormalities is also seen in vitamin B 12 deficiency and appears to be due to an undefined defect involving myelin synthesis. (From Cecil Textbook of Medicine, 19th ed, p848)
A compound containing several or all of the B-vitamins, including thiamine, riboflavin, niacin (nicotinic acid), niacinamide (nicotinamide), the vitamin B6 group (including pyridoxine, pyridoxal, pyridoxamine), biotin, pantothenic acid, folic acid, possibly para-aminobenzoic.
A condition due to deficiency in any member of the VITAMIN B COMPLEX. These B vitamins are water-soluble and must be obtained from the diet because they are easily lost in the urine. Unlike the lipid-soluble vitamins, they cannot be stored in the body fat.
A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.
A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406)
A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS.
A nutritional condition produced by a deficiency of VITAMIN E in the diet, characterized by posterior column and spinocerebellar tract abnormalities, areflexia, ophthalmoplegia, and disturbances of gait, proprioception, and vibration. In premature infants vitamin E deficiency is associated with hemolytic anemia, thrombocytosis, edema, intraventricular hemorrhage, and increasing risk of retrolental fibroplasia and bronchopulmonary dysplasia. An apparent inborn error of vitamin E metabolism, named familial isolated vitamin E deficiency, has recently been identified. (Cecil Textbook of Medicine, 19th ed, p1181)
A nutritional condition produced by a deficiency of VITAMIN K in the diet, characterized by an increased tendency to hemorrhage (HEMORRHAGIC DISORDERS). Such bleeding episodes may be particularly severe in newborn infants. (From Cecil Textbook of Medicine, 19th ed, p1182)
A vitamin found in green vegetables. It is used in the treatment of peptic ulcers, colitis, and gastritis and has an effect on secretory, acid-forming, and enzymatic functions of the intestinal tract.
A group of organic food substances found in animals and plants in small quantities. They must be supplied in diet or dietary supplement and are essential for normal metabolism.
A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached.
Detachment of the corpus vitreum (VITREOUS BODY) from its normal attachments, especially the retina, due to shrinkage from degenerative or inflammatory conditions, trauma, myopia, or senility.
Bleeding within the vitreous compartment of the eye.
A loss of the ability to move the vocal folds.
A non-neoplastic polypoid swelling of the vocal cord mucosa. It is usually unilateral and caused by excessive use of the voice.
A pathologic process in the larynx that affects the production of speech. Causes include vocal cord paresis, vocal cord nodule, vocal cord polyp, and laryngitis.
A type of permanent damage to muscles and nerves that results from prolonged lack blood flow to those tissues. It is characterized by shortening and stiffening of the muscles.
A twisting in the intestine (INTESTINES) that can cause INTESTINAL OBSTRUCTION.
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
A situation in which an individual vomits prior to a medical treatment, commonly chemotherapy, as part of a conditioned/learned response after having previously experienced nausea and/or vomiting as a direct result of that same (or a similar) treatment.
A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor.
Von Willebrand disease (VWD), a congenital bleeding disorder caused by deficient or defective plasma von Willebrand factor (VWF), may only become apparent on hemostatic challenge, and bleeding history may become more apparent with increasing age. Recent guidelines on VWD have recommended taking a VWF level of 30 or 40 IU/dL as a cut-off for those diagnosed with the disorder. Individuals with VWF levels greater than 30 IU/dL and lower than 50 IU/dL can be described as having a risk factor for bleeding. This change in guidelines significantly alters the proportion of individuals with each disease type. Type 1 VWD (~30% of VWD) typically manifests as mild mucocutaneous bleeding. Type 2 VWD accounts for approximately 60% of VWD. Type 2 subtypes include: Type 2A, which usually manifests as mild-to-moderate mucocutaneous bleeding; Type 2B, which typically manifests as mild-to-moderate mucocutaneous bleeding that can include thrombocytopenia that worsens in certain circumstances; Type 2M, which typically manifests as mild-moderate mucocutaneous bleeding; Type 2N, which can manifest as excessive bleeding with surgery and mimics mild hemophilia A. Type 3 VWD (<10% of VWD) manifests with severe mucocutaneous and musculoskeletal bleeding.
A disorder characterized by recurrent sexual urges, fantasies, or behaviors involving observing an unsuspecting person who is naked, disrobing, or engaging in sexual activity.
A non-neoplastic or neoplastic disorder that affects the vulva. Representative examples include infection, Bartholin gland adenoma, and vulvar carcinoma.
A benign or malignant neoplasm that affects the vulva. Representative examples include Bartholin gland adenoma, vulvar nodular hidradenoma, vulvar carcinoma, and vulvar melanoma.
Inflammation of the VULVA. It is characterized by PRURITUS and painful urination.
An inflammatory pathologic process that affects the vulva and the vagina.
A syndrome caused by an infarct in the vertebral or posterior inferior cerebellar artery. It is characterized by sensory defects affecting the same side of the face as the infarct and the opposite side of the trunk as the infarct. Patients experience difficulty swallowing and/or speaking.
A condition caused by degeneration, atrophy, and destruction of the distal part of a nerve fiber's axon and myelin, when continuity with the neural cell nucleus has been severed due to injury. Signs and symptoms include muscle weakness, altered sensation, and limb numbness.
A synthetic anticoagulant. Warfarin inhibits the regeneration of vitamin K1 epoxide and so the synthesis of vitamin K dependent clotting factors, which include Factors II, VII, IX and X, and the anticoagulant proteins C and S. This inhibition results in a sequential depression of Factors VII, IX, X and II activities. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K dependent clotting factors. The vitamin promotes the biosynthesis of gamma-carboxyglutamic acid residues in these proteins which are essential for biological activity.
A papillomavirus related epithelial overgrowth. It can be located anywhere on the body though when it involves the perineal region it is generally referred to as condyloma acuminata.
A condition of involuntary weight loss of greater then 10% of baseline body weight. It is characterized by atrophy of muscles and depletion of lean body mass. Wasting is a sign of MALNUTRITION as a result of inadequate dietary intake, malabsorption, or hypermetabolism.
A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A condition resulting from the excessive retention of water with sodium depletion.
Disturbances in the body's WATER-ELECTROLYTE BALANCE.
A condition of HEMORRHAGE and NECROSIS of the ADRENAL GLAND. It is characterized by rapidly developing ADRENAL INSUFFICIENCY; HYPOTENSION; and widespread cutaneous PURPURA.
Permanent deprivation of breast milk and commencement of nourishment with other food. (From Stedman, 25th ed)
A severe form of LEPTOSPIROSIS, usually caused by LEPTOSPIRA INTERROGANS SEROVAR ICTEROHAEMORRHAGIAE and occasionally other serovars. It is transmitted to humans by the rat and is characterized by hemorrhagic and renal symptoms with accompanying JAUNDICE.
Werner syndrome is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Individuals with Werner syndrome develop normally until the end of the first decade. The first sign is the lack of a growth spurt during the early teen years. Early findings (usually observed in the 20s) include loss and graying of hair, hoarseness, and scleroderma-like skin changes, followed by bilateral ocular cataracts, type 2 diabetes mellitus, hypogonadism, skin ulcers, and osteoporosis in the 30s. Myocardial infarction and cancer are the most common causes of death; the mean age of death in individuals with Werner syndrome is 54 years.
An acute neurological disorder characterized by the triad of ophthalmoplegia, ataxia, and disturbances of mental activity or consciousness. Eye movement abnormalities include nystagmus, external rectus palsies, and reduced conjugate gaze. THIAMINE DEFICIENCY and chronic ALCOHOLISM are associated conditions. Pathologic features include periventricular petechial hemorrhages and neuropil breakdown in the diencephalon and brainstem. Chronic thiamine deficiency may lead to KORSAKOFF SYNDROME. (Adams et al., Principles of Neurology, 6th ed, pp1139-42; Davis & Robertson, Textbook of Neuropathology, 2nd ed, pp452-3)
A mosquito-borne viral illness caused by the WEST NILE VIRUS, a FLAVIVIRUS and endemic to regions of Africa, Asia, and Europe. Common clinical features include HEADACHE; FEVER; maculopapular rash; gastrointestinal symptoms; and lymphadenopathy. MENINGITIS; ENCEPHALITIS; and MYELITIS may also occur. The disease may occasionally be fatal or leave survivors with residual neurologic deficits. (From Joynt, Clinical Neurology, 1996, Ch26, p13; Lancet 1998 Sep 5;352(9130):767-71)
A high-pitched whistling sound associated with labored breathing.
A congenital reproductive abnormality in white female offspring (heifers) in certain breeds of CATTLE, such as Belgian Blue and Shorthorn. The white color is inherited as a recessive trait which is associated with defects in the female reproductive tract (Muellerian system). These heifers are usually sterile.
A myodegeneration most frequent in calves and lambs whose dams have been fed during gestation or longer on feeds, especially legumes (FABACEAE), grown in certain areas where selenium is either deficient or unavailable in the soil. It has been recorded in many countries. It has been produced experimentally in several species of animals on low-selenium intake. A similar myopathy occurs naturally in goats, deer, foals, and dogs but proof of the etiology is lacking. (Merck Veterinary Manual, 5th ed)
A contagious bacterial respiratory infection caused by Bordetella pertussis. It is characterized by severe and uncontrollable cough, resulting in a whooping sound during breathing following the cough.
A type of cough characterized by a burst of numerous and rapid coughs followed by a long inhaling effort that is accompanied by a high-pitched whooping sound produced by the inhalation of air.
The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by pathogenic variants in WAS. WAS-related disorders usually present in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections, particularly of the ear. At least 40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura, immune-mediated neutropenia, rheumatoid arthritis, vasculitis, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), are at increased risk of developing lymphomas, which often occur in unusual, extranodal locations including the brain, lung, or gastrointestinal tract. Males with XLT have thrombocytopenia with small platelets; other complications of Wiskott-Aldrich syndrome, including eczema and immune dysfunction, are usually mild or absent. Males with XLN have congenital neutropenia, myeloid dysplasia, and lymphoid cell abnormalities.
A rheumatic syndrome of possibly allergic origin, usually affecting children and adolescents, and characterized by high fever, exanthema, arthralgia, leukocytosis, and increased sedimentation rate.
Wolff-Parkinson-White syndrome is a condition characterized by abnormal electrical pathways in the heart that cause a disruption of the heart's normal rhythm (arrhythmia).The heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. A specialized cluster of cells called the atrioventricular node conducts electrical impulses from the heart's upper chambers (the atria) to the lower chambers (the ventricles). Impulses move through the atrioventricular node during each heartbeat, stimulating the ventricles to contract slightly later than the atria.People with Wolff-Parkinson-White syndrome are born with an extra connection in the heart, called an accessory pathway, that allows electrical signals to bypass the atrioventricular node and move from the atria to the ventricles faster than usual. The accessory pathway may also transmit electrical impulses abnormally from the ventricles back to the atria. This extra connection can disrupt the coordinated movement of electrical signals through the heart, leading to an abnormally fast heartbeat (tachycardia) and other changes in heart rhythm. Resulting symptoms include dizziness, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, and fainting (syncope). In rare cases, arrhythmias associated with Wolff-Parkinson-White syndrome can lead to cardiac arrest and sudden death. The most common arrhythmia associated with Wolff-Parkinson-White syndrome is called paroxysmal supraventricular tachycardia.Complications of Wolff-Parkinson-White syndrome can occur at any age, although some individuals born with an accessory pathway in the heart never experience any health problems associated with the condition.Wolff-Parkinson-White syndrome often occurs with other structural abnormalities of the heart or underlying heart disease. The most common heart defect associated with the condition is Ebstein anomaly, which affects the valve that allows blood to flow from the right atrium to the right ventricle (the tricuspid valve). Additionally, the heart rhythm problems associated with Wolff-Parkinson-White syndrome can be a component of several other genetic syndromes, including hypokalemic periodic paralysis (a condition that causes episodes of extreme muscle weakness), Pompe disease (a disorder characterized by the storage of excess glycogen), Danon disease (a condition that weakens the heart and skeletal muscles and causes intellectual disability), and tuberous sclerosis complex (a condition that results in the growth of noncancerous tumors in many parts of the body).
WFS1-related disorders range from Wolfram syndrome (WFS) to WFS1-related low-frequency sensory hearing loss (also known as DFNA6/14/38 low-frequency sensorineural hearing loss [LFSNHL]). WFS is a progressive neurodegenerative disorder characterized by onset of diabetes mellitus and optic atrophy before age 16 years, and typically associated with sensorineural hearing loss, progressive neurologic abnormalities (cerebellar ataxia, peripheral neuropathy, dementia, psychiatric illness, and urinary tract atony), and other endocrine abnormalities. Median age at death is 30 years. WFS-like disease is characterized by sensorineural hearing loss, diabetes mellitus, psychiatric illness, and variable optic atrophy. WFS1-related LFSNHL is characterized by congenital, nonsyndromic, slowly progressive, low-frequency (<2000 Hz) sensorineural hearing loss.
The phenotypic spectrum of lysosomal acid lipase (LAL) deficiency ranges from the infantile-onset form (Wolman disease) to later-onset forms collectively known as cholesterol ester storage disease (CESD). Wolman disease is characterized by infantile-onset malabsorption that results in malnutrition, storage of cholesterol esters and triglycerides in hepatic macrophages that results in hepatomegaly and liver disease, and adrenal gland calcification that results in adrenal cortical insufficiency. Unless successfully treated with hematopoietic stem cell transplantation (HSCT), infants with classic Wolman disease do not survive beyond age one year. CESD may present in childhood in a manner similar to Wolman disease or later in life with such findings as serum lipid abnormalities, hepatosplenomegaly, and/or elevated liver enzymes long before a diagnosis is made. The morbidity of late-onset CESD results from atherosclerosis (coronary artery disease, stroke), liver disease (e.g., altered liver function ± jaundice, steatosis, fibrosis, cirrhosis and related complications of esophageal varices, and/or liver failure), complications of secondary hypersplenism (i.e., anemia and/or thrombocytopenia), and/or malabsorption. Individuals with CESD may have a normal life span depending on the severity of disease manifestations.
Infection of a break in the skin or other tissue.
A vasodilator used in peripheral vascular disorders and insufficiency. It may cause gastric discomfort and hypotension.
A benign histiocytic tumor that occurs during childhood; it is distinct from Langerhans cell histiocytosis. It is characterized by the presence of lipid-laden, foamy histiocytes and Touton-type giant cells in the dermis. The lesions usually develop during infancy. They consist of cutaneous papules and nodules (most often in the head and neck). It is sometimes associated with deep soft tissues nodules.
A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.
A xanthophyll found in the major LIGHT-HARVESTING PROTEIN COMPLEXES of plants. Dietary lutein accumulates in the MACULA LUTEA.
A colorless, heavy, odorless noble gas element with atomic symbol Xe, atomic number 54, and atomic weight 131.3.
A non-neoplastic disorder characterized by abnormally dry skin. Causes include vitamin A deficiency, sunlight exposure, medications, metabolic disorders, autoimmune disorders, and hereditary genetic disorders.
Xeroderma pigmentosum (XP) is characterized by: Sun sensitivity (severe sunburn with blistering, persistent erythema on minimal sun exposure in ~60% of affected individuals), with marked freckle-like pigmentation of the face before age two years in most affected individuals; Sunlight-induced ocular involvement (photophobia, keratitis, atrophy of the skin of the lids); Greatly increased risk of sunlight-induced cutaneous neoplasms (basal cell carcinoma, squamous cell carcinoma, melanoma). Approximately 25% of affected individuals have neurologic manifestations (acquired microcephaly, diminished or absent deep tendon stretch reflexes, progressive sensorineural hearing loss, and progressive cognitive impairment). The most common causes of death are skin cancer, neurologic degeneration, and internal cancer. The median age at death in persons with XP with neurodegeneration (29 years) was found to be younger than that in persons with XP without neurodegeneration (37 years).
Dryness of the eye due to inadequate production of tears. Causes include vitamin A deficiency, Sjogren syndrome, rheumatoid arthritis, systemic lupus erythematosus, and scleroderma.
A sulfamoylbenzamide analog of CLOPAMIDE. It is diuretic and saluretic with antihypertensive activity. It is bound to PLASMA PROTEINS, thus has a delayed onset and prolonged action.
An adrenergic alpha-2 agonist used as a sedative, analgesic and centrally acting muscle relaxant in VETERINARY MEDICINE.
A five-carbon sugar alcohol derived from XYLOSE by reduction of the carbonyl group. It is as sweet as sucrose and used as a noncariogenic sweetener.
Abnormal genetic constitution in males characterized by an extra Y chromosome.
An involuntary deep INHALATION with the MOUTH open, often accompanied by the act of stretching.
A systemic non-venereal infection of the tropics caused by TREPONEMA PALLIDUM subspecies pertenue.
A viral infection caused by a flavivirus called yellow fever virus. It is transmitted to humans from infected mosquitoes. The signs and symptoms range from a mild febrile illness to liver damage with jaundice and hemorrhages.
An infection that is caused by Yersinia enterocolitica or Yersinia pseudotuberculosis, and that is usually acquired by consumption of contaminated meat, water, or unpasteurized milk. It can also be transmitted vertically, pre- or perinatally, from mother to infant. Manifestation of symptoms depends on the infecting species and mode of acquisition, and can range from gastrointestinal syndromes to septicemia.
Infections with bacteria of the species YERSINIA PSEUDOTUBERCULOSIS.
An element of the rare earth family of metals. It has the atomic symbol Yb, atomic number 70, and atomic weight 173. Ytterbium has been used in lasers and as a portable x-ray source.
The fumarate salt of ketotifen, a cycloheptathiophene derivative with anti-allergic activity. Ketotifen selectively blocks histamine (H1) receptors and prevents the typical symptoms caused by histamine release. This agent also interferes with the release of inflammatory mediators from mast cells involved in hypersensitivity reactions, thereby decreasing chemotaxis and activation of eosinophils.
Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term ""ZSD"" is now used to refer to all individuals with a PEX gene defect regardless of phenotype. Individuals with ZSD usually come to clinical attention in the newborn period or later in childhood. Affected newborns are hypotonic and feed poorly. They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and other long bones), and liver disease that can be severe. Infants with severe ZSD are significantly impaired and typically die during the first year of life, usually having made no developmental progress. Individuals with intermediate/milder ZSD do not have congenital malformations, but rather progressive peroxisome dysfunction variably manifest as sensory loss (secondary to retinal dystrophy and sensorineural hearing loss); neurologic involvement (ataxia, polyneuropathy, and leukodystrophy); liver dysfunction; adrenal insufficiency; and renal oxalate stones. While hypotonia and developmental delays are typical, intellect can be normal. Some have osteopenia; almost all have ameleogenesis imperfecta in the secondary teeth.
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.
One of the SEROTONIN UPTAKE INHIBITORS formerly used for depression but was withdrawn worldwide in September 1983 because of the risk of GUILLAIN-BARRE SYNDROME associated with its use. (From Martindale, The Extra Pharmacopoeia, 29th ed, p385)
A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.
A mild astringent and topical protectant with some antiseptic action. It is also used in bandages, pastes, ointments, dental cements, and as a sunblock.
The zinc salt form of diethylene triamine pentaacetate (Zn-DTPA or pentetate zinc) with chelating activity. Upon administration, Zn-DTPA loses the Zn ion to form stable chelates with metal ions because DTPA has a higher affinity for heavy metal ions than for Zn ions. Specifically, this agent is able to bind to and form strong complexes with the radioactive plutonium, americium, and cerium after internal contamination. The formation of these heavy metal chelates enhances radionuclide excretion.
A pyrazolodiazepinone with pharmacological actions similar to ANTI-ANXIETY AGENTS. It is commonly used in combination with TILETAMINE to obtain immobilization and anesthesia in animals.
A condition in which there is increased production of gastrin by a gastrin-secreting tumor (usually located in the pancreas, duodenum, or abdominal lymph nodes) that stimulates the gastric mucosa to maximal activity, with consequent gastrointestinal mucosal ulceration.
Diseases of non-human animals that may be transmitted to HUMANS or may be transmitted from humans to non-human animals.
A uricosuric and muscle relaxant. Zoxazolamine acts centrally as a muscle relaxant, but the mechanism of its action is not understood.
Any infection due to a fungus of the Zygomycota phylum. The disease typically involves the rhino-facial-cranial area, lungs, gastrointestinal tract, skin, or less commonly other organ systems. The infecting fungi have a predilection for invading vessels of the arterial system, causing embolization and subsequent necrosis of surrounding tissue.
An aminobisphosphonate that inhibits BONE RESORPTION and is used for the treatment of osteolytic lesions, bone pain, and severe HYPERCALCEMIA associated with malignancies.
A synthetic analog of vitamin D with potential antineoplastic activity. In the liver, doxercalciferol is converted to its biologically active vitamin D metabolites, which control the intestinal absorption of dietary calcium, the tubular reabsorption of calcium by the kidney and, in conjunction with parathyroid hormone (PTH), the mobilization of calcium from the skeleton. Through interaction with specific receptor proteins in target tissues, these vitamin D metabolites act directly on osteoblasts to stimulate skeletal growth, and on the parathyroid glands to suppress PTH synthesis and secretion. This agent has also been shown to inhibit the growth of retinoblastomas, and may exhibit some antiproliferative activity against prostate cancer cells.
A synthetic triepoxide alkylating agent with potential antineoplastic activity. Anaxirone alkylates DNA via actual or derived epoxide groups, resulting in inhibition of DNA synthesis. This agent has been shown to exhibit a broad spectrum of antineoplastic activity against experimental tumors, including those resistant to other alkylating agents.
A synthetic oil with anti-obesity activity. The enzymatically synthesized isoform, 1,3-isoform diacylglycerol, is suggested to decrease formation of chylomicrons as well as shunting them directly to the liver through the portal vein where they are oxidized. Increased beta-oxidation may enhance body weight loss, suppress body fat accumulation and lower serum triacylglycerol levels through increasing satiety.
A synthetic spironolactone analogue and progestin with progestational and anti-mineralocorticoid activity. Drospirenone binds to the progesterone receptor, the resulting complex becomes activated and binds to specific sites on DNA. This results in a suppression of LH activity and an inhibition of ovulation as well as an alteration in the cervical mucus and endometrium. This leads to an increased difficulty of sperm entry into the uterus and implantation. This drug is used in oral contraceptives.
A pyridone derivative and iron chelator that is used in the treatment of IRON OVERLOAD in patients with THALASSEMIA.
A triazene triepoxide with antineoplastic activity. Teroxine alkylates and cross-links DNA, thereby inhibiting DNA replication. (NCI04)
An aziridinyl-substituted cyclophosphazene and a putrescence derivative that may cause DNA cross-linkage. (NCI04)
An antiseptic agent with potential antibacterial and antileukemic activity. Although the exact mechanism of action remains to be fully elucidated, ambazone appears to interfere with the membrane-bound nucleotide system by increasing the intracellular concentration of cAMP in leukemia cells and macrophages, which potentially contributes to this agent's antineoplastic activity. Furthermore, this agent's affinity for various cellular targets, i.e. membranes, nucleic acids and proteins, may contribute to the overall antibacterial effect.
A water-soluble taurine-based nitrosourea with potential antineoplastic activity. Tauromustine alkylates DNA and causes DNA cross links independent of cell cycle, thereby resulting in disruption of DNA function and induction of apoptosis.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
An antimetabolite (pyrimidine analogue) antineoplastic derivative of 5-fluorouracil. (NCI)
A synthetic analog of lysophosphatidylcholine, an ether lipid, possessing anti-leishmanial and antineoplastic activity. The mechanism of action for edelfosine has not been fully elucidated. Targeting cellular membranes, edelfosine modulates membrane permeability, membrane lipid composition, and phospholipid metabolism. Edelfosine also inhibits the phosphatidylinositol 3 kinase (PI3K)-AKT/PKB survival pathway, possibly activating the pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis. In addition, this agent inhibits protein kinase C, intracellular activation of the Fas/CD95 receptor, and intracellular acidification. Anti-leishmanial activity may be due to inhibition of a glycosomal alkyl-specific-acylCoA acyltransferase. (NCI)
The 10-butyryl derivative of dithranol with antipsoriatic activity.
A polyglutamatable folate antagonist analogue of methotrexate with antineoplastic activity. Edatrexate inhibits dihydrofolate reductase, thereby increasing cellular levels of polyglutamates, inhibiting thymidylate synthase and glycinamide ribonucleotide formyl transferase, impairing synthesis of purine nucleotides and amino acids, and resulting in tumor cell death. Edatrexate may overcome tumor resistance to methotrexate, which loses its activity after it is polyglutamated. (NCI04)
A monohydroxy fatty acid resulting from the oxidation of linoleic acid or 13-hydroperoxy-9,11-octadecadienoic acid (13-HpODE). 13-HODE may mediate physiological and pathological responses and is a potential biomarker of various human diseases, and could contribute to the progression of certain diseases.
A branched-chain saturated fatty acid that is comprised of tetradecanoic acid with a methyl group on the carbon in the thirteenth position.
A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)
A synthetic progestational agent similar to the endogenous progesterone used in hormone therapy or as a female contraceptive. Mimicking the action of progesterone, hydroxyprogesterone caporate binds to and activates nuclear progesterone receptors in the reproductive system and causes the ligand-receptor complex to be translocated to the nucleus where it binds to and promotes expression of target genes. Due to the negative feedback mechanism seen with progesterone, this agent also blocks luteinizing hormone (LH) release from the pituitary gland, thereby leading to an inhibition of ovulation and an alteration in the cervical mucus and endometrium. Furthermore, without stimulation of LH, estrogen release from the ovaries is stopped, hence impeding the growth of estrogen-sensitive tumor cells.
A metabolite of PROGESTERONE with a hydroxyl group at the 17-alpha position. It serves as an intermediate in the biosynthesis of HYDROCORTISONE and GONADAL STEROID HORMONES.
A steroid progestin derivative with antigonadotropic activity. 19-nor-Progesterone decreases luteinizing hormone (LH) and follicle stimulatory hormone (FSH) secretion, which are effects likely mediated through the binding of this agent to the progesterone receptor. The antigonadotropic activity of this hormone results in reinforcement of its antiestrogenic activity, allowing treatment of the clinical hyper-estrogenic symptoms of peri-menopause without negative metabolic or hemostatic effects. 19-nor-Progesterone, in addition to its inhibitory effect on ovulation, induces changes in the endometrium, rendering it resistant to implantation, and in the cervical mucus, rendering it hostile to spermatozoa migration. This agent is also a potent mineralocorticoid. (NCI04)
A broad-spectrum antimetabolite and deoxycytidine analogue with antineoplastic activity. Upon administration, gemcitabine is converted into the active metabolites difluorodeoxycytidine diphosphate (dFdCDP) and difluorodeoxycytidine triphosphate (dFdCTP) by deoxycytidine kinase. dFdCTP competes with deoxycytidine triphosphate (dCTP) and is incorporated into DNA. This locks DNA polymerase thereby resulting in ""masked termination"" during DNA replication. On the other hand, dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis. The reduction in the intracellular concentration of dCTP potentiates the incorporation of dFdCTP into DNA.
An oligonucleotide synthesized from adenosine triphosphate (ATP) by enzymes in the 2'-5'-oligoadenylate synthase family. The production of 2'-5'-oligoadenylate is stimulated by the presence of double stranded RNA (dsRNA) and binds to inactive monomeric forms of ribonuclease L (RNase L), thereby promoting RNase L dimerization and activation. Active RNase L degrades both cellular and viral RNAs, which inhibits protein translation and leads to the abrogation of viral replication. 2'-5'-oligoadenylates play a key role in the innate immunity against viruses.
A pyrimidine nucleoside analog with activity against various herpesviruses. Fiacitabine is converted to its triphosphate form in vivo and inhibits viral DNA polymerase.
A synthetic pyrimidine analogue with activity against hepatitis B virus (HBV). Intracellularly, clevudine is phosphorylated to its active metabolites, clevudine monophosphate and triphosphate. The triphosphate metabolite competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). Clevudine has a long half-life and shows significant reduction of covalently closed circular DNA (cccDNA), therefore the patient is less likely to have a relapse after treatment is discontinued.
A hydrolysis product of mustard gas, an alkylating agent, with antineoplastic activity.
A synthetic agent, also known as IMPY, with antineoplastic properties. IMPY inhibits ribonucleotide reductase, an enzyme that converts ribonucleotides to deoxyribonucleotides during DNA synthesis; this agent specifically binds the smaller, nonheme-iron subunit of the enzyme. (NCI04)
One of a number of organic compounds that share a similar purine structure and possess antiviral and antitumor properties. 2,6-Diaminopurine nucleosides are versatile synthetic precursors for specific N-6 modifications of antiviral and antitumor agents. (NCI04)
A methoxy-substituted benzoquinone and bioactive compound found in fermented wheat germ extracts, with potential antineoplastic and immune-enhancing activity. 2,6-Dimethoxyquinone (2,6-DMBQ) inhibits anaerobic glycolysis thereby preventing cellular metabolism and inducing apoptosis. As cancer cells use the anaerobic glycolysis pathway to metabolize glucose and cancer cells proliferate at an increased rate as compared to normal, healthy cells, this agent is specifically cytotoxic towards cancer cells. In addition, 2,6-DMBQ exerts immune-enhancing effects by increasing natural killer (NK) cell and T-cell activity against cancer cells.
An alkylating chloroethylnitrosourea with antineoplastic activity. Selectively accumulating in some tumor cells, SarCNU forms covalent linkages with nucleophilic centers in DNA, causing depurination, base pair miscoding, strand scission, and DNA-DNA cross-linking, which may result in cytotoxicity. (NCI04)
A synthetic pyridinyl bisphosphonate with anti-resorptive activity. Although the exact mechanism of action has yet to be fully elucidated, piridronic acid likely binds to hydroxyapatite crystals in the bone matrix and inhibits farnesyl pyrophosphate synthase, an enzyme that plays an important role in the mevalonate pathway. This inhibits the formation of isoprenoid metabolites that are substrates for protein prenylation. This prevents farnesylation and geranylgeranylation of proteins essential for osteoclast function, leading to the induction of apoptosis and eventually, osteoclast-cell death. By preventing osteoclast-mediated bone resorption, piridronic acid decreases bone turnover and stabilizes the bone matrix.
A synthetic antifungal and antibacterial agent used as a topical preparation.
A metabolite formed during the metabolism of 17beta-estradiol by hydroxylation of the carbon at position 2 by the CYP450 enzymes 1A1/1A2. Theoretically, 2-hydroxyestradiol (2-OHE2) is able to undergo redox cycling, which generates active radicals and induces DNA damage; however, this estradiol metabolite is very unstable in vivo and is quickly inactivated by catechol-O-methyltransferase (COMT)-mediated O-methylation and converted to 2-methoxyestradiol (2-MeE2). 2-MeE2 exerts antineoplastic activities through its estrogen receptor antagonistic effect and the induction of apoptosis in susceptible cancer cells.
A metabolite formed during the catabolism of estrone by the liver through the hydroxylation of the carbon at position 2 by cytochrome P450 (CYP) enzymes, including CYP1A1 and 1A2, with potential anticarcinogenic activity. The mechanism of action for the antitumor activity of 2-hydroxyestrone is not known but this metabolic product has minimal estrogenic activity compared to the parent compound and other estrone metabolites. Additionally, O-methylation of this compound produces 2-methoxyestradiol (2-MeOE2), which is a potent inhibitor of both cell proliferation and angiogenesis.
Derivative of beta-cyclodextrin that is used as an excipient for steroid drugs and as a lipid chelator.
An orally bioavailable estradiol metabolite with potential antineoplastic activity. 2-Methoxyestradiol inhibits angiogenesis by reducing endothelial cell proliferation and inducing endothelial cell apoptosis. This agent also inhibits tumor cell growth by binding to tubulin, resulting in antimitotic activity, and by inducing caspase activation, resulting in cell cycle arrest in the G2 phase, DNA fragmentation, and apoptosis. (NCI04)
A metabolite formed during the methylation of 2-hydroxyestrone (2-OHE1) by catechol-O-methyltransferase (COMT), with potential anticarcinogenic and minimal estrogen activities. The mechanism of action for the antitumor activity of 2-methoxyestrone (2-OMeE1) is not known. A high 2-methoxyestrone (2-OMeE1)/2-OHE1 ratio indicates higher methylation efficiency and correlates with a lower cancer risk.
An orally active inhibitor of long-chain fatty acid oxidation with hypoglycemic activity. By inhibiting fatty acid oxidation, palmoxiric acid increases carbohydrate oxidation attributed to the glucose-fatty acid cycle (Randle cycle) resulting in decreased blood glucose levels.
A chlorinated methotrexate derivative. Dichloromethotrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylates and inhibiting DNA and RNA synthesis. This agent is metabolized and excreted by the liver. (NCI04)
A nucleoside reverse transcriptase inhibitor with activity against hepatitis B virus (HBV) and human immunodeficiency virus (HIV). Lagociclovir is a prodrug of 3'-fluoro-2', 3'-dideoxyguanosine with high oral bioavailability and is converted to its triphosphate form in vivo. Lagociclovir is active against multiresistant HBV and HIV.
4-Aminopyridine derivative that acts as a POTASSIUM CHANNEL blocker to increase release of ACETYLCHOLINE from nerve terminals. It is used in the treatment of CONGENITAL MYASTHENIC SYNDROMES.
A purine nucleoside analogue with antineoplastic and antiviral activities. By replacing guanine, dezaguanine incorporates into DNA and inhibits de novo purine synthesis, thereby inducing cell death. (NCI)
A phenolic analogue of tamoxifen, a nonsteroidal selective estrogen receptor modulator (SERM). Droloxifene competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. (NCI)
A guanidine analog with specific affinity for tissues of the sympathetic nervous system and related tumors. The radiolabeled forms are used as antineoplastic agents and radioactive imaging agents. (Merck Index, 12th ed) MIBG serves as a neuron-blocking agent which has a strong affinity for, and retention in, the adrenal medulla and also inhibits ADP-ribosyltransferase.
A non-metabolizable glucose analogue that is not phosphorylated by hexokinase. 3-O-Methylglucose is used as a marker to assess glucose transport by evaluating its uptake within various cells and organ systems. (J Neurochem 1993;60(4):1498-504)
A synthetic form of the naturally occurring female sex hormone progesterone. Etonogestrel binds to the cytoplasmic progesterone receptors in the reproductive system and subsequently activates progesterone receptor mediated gene expression. As a result of the negative feedback mechanism, luteinizing hormone (LH) release is inhibited, which leads to an inhibition of ovulation and an alteration in the cervical mucus and endometrium.
An iodinated doxorubicin analogue with antiamyloid activity. 4'-Iodo-4'-deoxydoxorubicin (IDOX) binds with high affinity to five types of natural amyloid fibrils including immunoglobulin light chains, amyloid A, transthyretin (methionine-30 variant), beta-protein (Alzheimer), and beta2-microglobulin. This agent may inhibit fibril growth, increasing the solubility of amyloid tissue deposits and facilitating their clearance. IDOX has also been shown to insulin amyloid fibrillogenesis in vitro.
A synthetic derivative of the anthracycline antineoplastic antibiotic doxorubicin with potential antineoplastic activity. Esorubicin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis. This agent exhibits less cardiotoxicity than the parent antibiotic doxorubicin, but may cause more severe myelosupression compared to other compounds within the anthracycline class.
A brown to violet colored solid aromatic amine that emits toxic fumes of nitrogen oxides, carbon monoxide, carbon dioxide, nitrogen and sulfur oxides when heated to decomposition. 4,4'-Thiodianiline is primarily used as a chemical intermediate in the production of certain dyes. Exposure to this substance is irritating to the respiratory tract and can result in methemoglobinemia causing headache, dizziness, weakness and can lead to shortness of breath, collapse and even death. 4,4'-Thiodianiline is a possible mutagen and is reasonably anticipated to be a human carcinogen. (NCI05)
A yellowish crystalline solid nitrosamine that naturally occurs in tobacco products by oxidation and nitrosation of nicotine during the making and smoking of tobacco. 4-Methylnitrosamino-1,3-pyridyl-1-butanone is only used as a research chemical to induce tumorigenesis. This substance is reasonably anticipated to be a human carcinogen. (NCI05)
A cyclophosphamide synergizer with antineoplastic, antidiabetic, antihypertensive and immunopotentiating activity. Benaxibine is active against integrin alph-4 precursor.
A clonidine derivative with selective alpha-2-adrenergic agonistic activity. Upon ocular administration, apraclonidine enhances aqueous humor uveoscleral outflow and decreases aqueous production by vasoconstriction. This may decrease intraocular pressure (IOP).
An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID and is used as an anticonvulsant. (From Martindale The Extra Pharmacopoeia, 31st ed)
A synthetic steroidal substance with antineoplastic activity. Formestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. (NCI04)
A synthetic derivate of hydroquinone and depigmenting agent. Although the exact mechanism of the depigmenting effects of mequinol remains unclear, it may exert its effect by oxidation of tyrosinase to cytotoxic products in melanocytes. Mequinol may also act by competitively inhibiting the formation of melanin precursors.
A synthetic derivative of L-arginine with antithrombotic activity. Argatroban is a univalent and direct inhibitor of fibrin-bound thrombin. This agent reversibly binds to the thrombin active site thereby preventing the thrombin-dependent reactions, which include conversion of fibrinogen to fibrin; the activation of factors V, VIII and XI; the activation of protein C; and platelet aggregation. Argatroban is highly selective for thrombin and is able to inhibit the action of both free and clot-associated thrombin. As a result, stabilization of blood clots and coagulation is inhibited.
A pyrazole and competitive inhibitor of ALCOHOL DEHYDROGENASE that is used for the treatment of poisoning by ETHYLENE GLYCOL or METHANOL.
A synthetic derivative of estradiol. 4-nitroestrone 3-methyl ether inhibits estrogen sulfotransferase (EST), a progesterone-induced secretory endometrial enzyme which affects estrogen receptor levels. This agent has been shown to be an effective growth inhibitor of some chemically induced animal mammary tumors. (NCI04)
A fluoropyrimidine derivative and oral prodrug of the antineoplastic agent 5-fluorouracil (5-FU) with antitumor activity. Doxifluridine, designed to circumvent the rapid degradation of 5-FU by dihydropyrimidine dehydrogenase in the gut wall, is converted into 5-FU in the presence of pyrimidine nucleoside phosphorylase. 5-FU interferes with DNA synthesis and subsequent cell division by reducing normal thymidine production and interferes with RNA transcription by competing with uridine triphosphate for incorporation into the RNA strand.
A folate analog antimetabolite with antineoplastic activity. As the 6R diastereomer of 5,10-dideazatetrahydrofolate, lometrexol inhibits glycinamide ribonucleotide formyltransferase (GARFT), the enzyme that catalyzes the first step in the de novo purine biosynthetic pathway, thereby inhibiting DNA synthesis, arresting cells in the S phase of the cell cycle, and inhibiting tumor cell proliferation. The agent has been shown to be active against tumors that are resistant to the folate antagonist methotrexate. (NCI04)
A folate-based biomodulator with potential antineoplastic activity. 5,10-methylenetetrahydrofolate (MTHF) stabilizes the covalent binding of the fluorouracil metabolite 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (FdUMP) to its target enzyme, thymidylate synthase, which results in inhibition of thymidylate synthase, depletion of thymidine triphosphate (TTP), a necessary constituent of DNA, and tumor cell death. Unlike leucovorin, MTHF, as the active form of folate, does not require metabolic activation and may increase the chemotherapeutic effects of fluorouracil with lower toxicity.
A synthetic nucleoside analogue of deoxycytidine. Dihydro-5-azacytidine inhibits DNA methyltransferase, thereby interfering with abnormal DNA methylation patterns that are associated with genetic instability in some tumor cells. Inhibition of this enzyme may restore expression of tumor-suppressor genes and result in antitumor activity. (NCI04)
A cytidine antimetabolite analogue with potential antineoplastic activity. Decitabine incorporates into DNA and inhibits DNA methyltransferase, resulting in hypomethylation of DNA and intra-S-phase arrest of DNA replication. (NCI04)
A chlorinated heterocyclic sulfanilamide with potential antineoplastic activity and potential immunosuppressive activity. Chloroquinoxaline sulfonamide poisons topoisomerase II alpha and topoisomerase II beta, thereby causing double-stranded breaks in DNA, accumulation of unrepaired DNA, and apoptosis. This agent also exhibits lymphotoxicity by inhibiting lymphocyte activation in a cell cycle-specific manner. (NCI04)
An antimetabolite consisting of a fluorinated pyrimidine analog with potential antineoplastic activity. As a prodrug, 5-fluoro-2-deoxycytidine is converted by intracellular deaminases to the cytotoxic agent 5-Fluorouracil (5-FU). 5-FU is subsequently metabolized to active metabolites including 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP binds to and inhibits thymidylate synthase, thereby reducing the production of thymidine monophosphate, which leads to depletion of thymidine triphosphate. This inhibits DNA synthesis and cell division. FUTP competes with uridine triphosphate for incorporation into the RNA strand thus leading to an inhibition of RNA and protein synthesis. Other fluorouracil metabolites also get incorporated into both DNA and RNA, thereby further hampering cellular growth.
A Cytosine Arabinoside derivative that inhibits pyrimidine synthesis, causing inhibition of DNA synthesis. (NCI)
An iodinated analog of deoxycytidine used topically in the treatment of herpes labialis.
A linear furanocoumarin that has phototoxic and anti-inflammatory properties, with effects similar to METHOXSALEN. It is used in PUVA THERAPY for the treatment of PSORIASIS.
An antiprotozoal agent that was used in combination with tibroquinol. The combination agent was withdrawn from the market because of hepatoxicity.
A synthetic nonaromatizable androgen analog of testosterone. Fluorotestosterone (6 alpha-fluorotestosterone) binds to and activates specific nuclear receptors inhibits and is equipotent to testosterone. (NCI04)
A piperazinoazepine tetracyclic compound that enhances the release of NOREPINEPHRINE and SEROTONIN through blockage of presynaptic ALPHA-2 ADRENERGIC RECEPTORS. It also blocks both 5-HT2 and 5-HT3 serotonin receptors and is a potent HISTAMINE H1 RECEPTOR antagonist. It is used for the treatment of depression, and may also be useful for the treatment of anxiety disorders.
A furanyl adenine found in PLANTS and FUNGI. It has plant growth regulation effects.
A fluorescent nucleic acid dye which selectively binds GC sequences in double-stranded DNA. It has a molecular weight of 1270.5, an absorbance maximun at 546 nm, and emission maximum at 647 nm. It is commonly used to discriminate viable from non-viable cells.
An antimetabolite and a chlorine derivative of the intracellular secondary messenger, cyclic adenosine 3,5-monophosphate (cAMP), with potential antineoplastic activity. Tocladesine appears to be converted to 8-chloro-adenosine by phosphodiesterases and subsequently phosphorylated to 8-chloro-ATP, which functions as a purine analogue and competes with ATP in transcription. In addition, generation of 8-chloro-ATP depletes endogenous ATP pool that is essential for many biological reactions in intracellular energy transfer. As a result, this agent causes RNA synthesis inhibition, blocks cellular proliferation, and induces apoptosis.
A serotonin 1A-receptor agonist that is used experimentally to test the effects of serotonin.
A polycyclic aromatic hydrocarbon derived from anthracene or phthalic anhydride. Anthraquinone is used in the manufacture of dyes, in the textile and pulp industries, and as a bird repellant.
A nucleoside reverse transcriptase inhibitor analog of adenosine with activity against hepatitis B virus (HBV), herpes virus, and human immunodeficiency virus (HIV).
An acyclic guanosine analog with activity against herpes simplex virus (HSV). Buciclovir is phosphorylated to its triphosphate form by HSV thymidine kinase in infected cells and acts as a specific inhibitor of the viral DNA polymerase. It is incorporated into both RNA and DNA but only inhibits DNA synthesis.
A pseudotetrasaccharide and inhibitor of alpha-glucosidase and pancreatic alpha-amylase with antihyperglycemic activity. Acarbose binds to and inhibits alpha-glucosidase, an enteric enzyme found in the brush border of the small intestines that hydrolyzes oligosaccharides and disaccharides into glucose and other monosaccharides. This prevents the breakdown of larger carbohydrates into glucose and decreases the rise in postprandial blood glucose levels. In addition, acarbose inhibits pancreatic alpha-amylase which hydrolyzes complex starches to oligosaccharides in the small intestines.
A derivative of D-glucaro-1, 4-lactone with chemopreventive and anti-tumor activities. One of the key processes in which human body eliminates toxic chemicals as well as hormones (such as estrogen) is by glucuronidation. When beta-glucuronidase deconjugates these glucuronides, it prolongs the stay of the hormone or toxic chemical in the body. Elevated beta-glucuronidase activity has been implicated to be associated with an increased risk for hormone-dependent cancers like breast, prostate, and colon cancers. Thereby, aceglatone may suppress the developments of hormone-dependent cancers mediated through beta-glucuronidase inhibition.
used as a solvent, plasticizer, and a wetting and penetrating agent; formula, C2H5NO.
A pentavalent arsenical compound with antiprotozoal and antihelmintic properties. Although its mechanism of action is not fully known, acetarsone may bind to protein-containing sulfhydryl groups located in the parasite, thereby forming lethal As-S bonds. This may prevent their functioning and eventually kill the parasite.
A synthetic acetylenic carbamate, an alkylating agent, with antineoplastic activity.
A niacin derivative and nicotinic acid analog with activity as a hypolipidemic agent. Acipimox has special application for the treatment of hyperlipidemia in non-insulin-dependent diabetic patients.
An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of ETRETINATE with the advantage of a much shorter half-life when compared with etretinate.
A modified amino acid and structural analog of glutamine. Acivicin inhibits glutamine amidotransferases in the purine and pyrimidine biosynthetic pathways, thereby inhibiting tumor growth in cell lines dependent on glutamine metabolism. (NCI04)
A synthetic imidazoquinoline with antineoplastic activity. Acodazole intercalates into DNA, resulting in disruption of DNA replication. Use of this agent has been associated with significant cardiotoxicity. (NCI04)
A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.
A long-acting, selective, reversible inhibitor of dihydrofolate reductase with application as a broad-spectrum antibacterial agent in animals.
An insoluble fraction isolated from the bacterium Corynebacterium granulosum with potential cancer immunotherapeutic activity. As a non-specific immunostimulant, Corynebacterium granulosum P40 activates the reticuloendothelial system, induces the production of certain cytokines, enhances macrophage activity, and potentiates a delayed-type hypersensitivity response when co-administered with an antigen. (NCI04)
A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers.
A monobenzyl ether of hydroquinone with topical depigmentation activity. Although the exact mechanism of action of depigmentation is unknown, the metabolites of monobenzone appear to have a cytotoxic effect on melanocytes. Furthermore, the depigmentation effect might be mediated through the inhibition of tyrosinase, which is essential in the synthesis of melanin pigments, thereby causing permanent depigmentation of the skin.
A 5-aminoimidazole-4-carboxamide (AICA) riboside, a ribnucleoside analog, and a nucleotide biosynthesis precursor with B cell pro-apoptotic activity. Following cellular uptake, acadesine is phosphorylated to AICA ribotide (ZMP), which mimics 5'-adenosine monophosphate (AMP). Both AMP-activated protein kinase (AMPK) and AMPK kinase (AMPKK) are activated by ZMP, which appears to be necessary for the induction of apoptosis. Acadesine-induced apoptosis also appears to require cytochrome c release from mitochondria and caspase activation and is p53-independent. However, the exact mechanism of acadesine-induced apoptosis is unknown. T cells are significantly less susceptible than B cells to acadesine-induced apoptosis. AMPK regulates several cellular systems including the cellular uptake of glucose, the beta-oxidation of fatty acids, protein synthesis, and the biogenesis of glucose transporter 4 (GLUT4) and mitochondria.
A long-acting, sulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, alacepril is rapidly metabolized to captopril; captopril competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Captopril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
An amino acid analogue and antibiotic derived from the bacterium Streptomyces alanosinicus with antimetabolite and potential antineoplastic activities. L-alanosine inhibits adenylosuccinate synthetase, which converts inosine monophospate (IMP) into adenylosuccinate, an intermediate in purine metabolism. L-alanosine-induced disruption of de novo purine biosynthesis is potentiated by methylthioadenosine phosphorylase (MTAP) deficiency. The clinical use of this agent may be limited by its toxicity profile. MTAP is a key enzyme in the adenine and methionine salvage pathways.
A nutritional supplement containing a stable, water-soluble dipeptide comprised of the amino acids L-glutamine and L-alanine, with potential protective and absorption enhancing activities. Upon oral or enteral administration, alanylglutamine works locally in the gastrointestinal (GI) tract to both protect the integrity of the intestinal mucosa and maintain intestinal barrier functions. This reduces bacterial translocation, the risk of infection, infection-induced inflammatory damage and infection-associated symptoms, such as diarrhea, dehydration, malabsorption and electrolyte imbalances. Alanylglutamine also increases absorption of other chemicals, enhances epithelial repair, and inhibits apoptosis due to cellular damage, and stimulates cellular proliferation. Altogether, this improves absorption of nutrients, decreases weight loss, reduces diarrhea, decreases the risk of GI-associated infections and improves recovery. Upon absorption, alanylglutamine may also help inhibit muscle protein catabolism.
The dipropionate salt form of alclometasone, a synthetic corticosteroid with low to medium potency. Alclometasone dipropionate is a glucocorticoid receptor agonist that mimics the metabolic, anti-inflammatory, immunosuppressive, antipruritic, and vasoconstrictive effects of natural glucocorticoids. This drug interacts with specific intracellular receptors and binds to DNA to modify gene expression. This results in an induction of synthesis of certain proteins while inhibiting the synthesis of others. Alclometasone dipropionate is used for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. (NCI05)
An aluminum salt formulation of clofibrate, an aryloxyisobutyric acid derivate with antihyperlipidemic activity.
A synthetic quinazoline compound with smooth muscle relaxing activity. Alfuzosin selectively binds to and antagonizes alpha-1-adrenergic receptors in smooth muscle of the bladder neck and prostate, thereby relaxing the smooth muscle and decreasing the obstruction and urethral resistance seen with benign prostate hyperplasia (BPH) and prostate cancer. This agent also blocks alpha-1-adrenergic receptors in peripheral vascular smooth muscle, which leads to vasodilatation and a subsequent decrease in peripheral vascular resistance.
A polysaccharide and linear copolymer, consisting mainly of beta-1,4-linked D-mannuronic acid and alpha-1,4-linked L-glucuronic acid, that occurs in marine algae such as LAMINARIA, and in BIOFILMS produced by PSEUDOMONAS AERUGINOSA.
A substituted benzamide that acts as a dopamine receptor antagonist with antiemetic properties.
An allyl-S-compound with the structure C=CCS(=O)SCC=C.
An antimitotic agent that binds to tubulin and inhibits tubulin polymerization and arrests proliferation of tumor cells.
An isothiocyanate with an allyl group (-C-C=C). The chemical structure is C=CCN=C=S.
An allyl-S compound with the structure C=CCSCC=C.
A purine analog with potential antineoplastic activity. (NCI04)
An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies.
An inhibitor of the enzyme TYROSINE 3-MONOOXYGENASE, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with PHEOCHROMOCYTOMA. (Martindale, The Extra Pharmacopoeia, 30th ed)
An agent, also known as altizide, belonging to the class of thiazide diuretics with antihypertensive activity.
A topical astringent that is used as an antiseptic agent. Aluminum acetate is used to treat inflammation, itching, and stinging of the infected skin and promotes healing.
An aluminum salt of sulfuric acid, an industrial chemical used in many industrial applications. In purification of drinking water, aluminum sulfate acts as a flocculating agent which causes impurities to coagulate and sediment, so that they are easily removed by filtration. It is also used as a mordant in textile dyeing and paper manufacture.
A natural polyketide isolated from the myxobacteria Sorangium cellulosum with antifungal activity. Ambruticin interferes with the osmoregulatory system by activating fungal high osmolarity glycerol (HOG) pathway. This results in an accumulation of intracellular glycerol, which in turn causes water influx and swelling of the cell. This ultimately leads to cellular leakage and cell death.
A synthetic glucocorticoid receptor agonist that mimics the metabolic, anti-inflammatory, and immunosuppressive activity of the natural glucocorticoids. Amcinonide interacts with specific corticosteroid receptors and was internalized, which leads to binding of DNA and modification of gene expression. This results in synthesis of anti-inflammatory mediators while inhibiting synthesis of inflammatory mediators. Consequently, an overall reduction in chronic inflammation and autoimmune reactions are achieved.
An orally available antiprotozoan agent used in the treatment of vaginal trichomoniasis.
A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.
The hydroxy salt of ammonium ion. It is formed when AMMONIA reacts with water molecules in solution.
An imide derivative of naphthalic acid. Amonafide intercalates into DNA and inhibits topoisomerase II, resulting in protein-associated strand breaks and impaired DNA and RNA synthesis.
A morpholine antifungal agent for topical use. Amorolfine inhibits delta-14-reductase and delta-7,8-isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membrane.
The deoxycholate salt of amphotericin B, a polyene antifungal antibiotic produced by Streptomyces nodosus, with antifungal activity. Amphotericin B binds to ergosterol, an essential component of the fungal cell membrane. This results in depolarization of the cell membrane, alterations in cell membrane permeability, leakage of important intracellular components, and cell rupture. This agent may also induce oxidative damage in fungal cells and has been reported to stimulate host immune cells.
A synthetic quinazoline derivative, Anagrelide reduces platelet production through a decrease in megakaryocyte maturation. Anagrelide inhibits cyclic AMP phosphodiesterase, as well as ADP- and collagen-induced platelet aggregation. At therapeutic doses, it does not influence white cell counts or coagulation parameters. Anagrelide is used for treatment of essential thrombocythemia to reduce elevated platelet counts and the risk of thrombosis. (NCI04)
An alkaloid found in low concentrations in plants in the Solanaceae family, which includes tobacco and tomato plants, with potential nicotine mimetic and anti-inflammatory activities. Following oral administration, anatabine may mimic the neurological effects of nicotine exposure. This agent may not have the addictive properties of nicotine; therefore, it may be appropriate for use in treating nicotine withdrawal symptoms during smoking cessation. Anatabine may also exert its anti-inflammatory effect by the inhibition of the signal transducer and activator of transcription 3 (STAT3) which then prevents the activation of the nuclear factor kappa B (NF-kB), which is a key regulator of proinflammatory cytokine release. Urine concentrations of anatabine can be used to assess the extent of tobacco use.
A labdane diterpenoid that is produced by the Andrographis paniculata plant, which has a broad range of therapeutic applications including anti-inflammatory and anti-platelet aggregation activities and potential antineoplastic properties. Since andrographolide has multiple therapeutic activities there are several proposed mechanisms of action for this agent. The anti-inflammatory effects of this agent appear to be related to the inhibition of nitric oxide (NO) production by macrophages. This agent may activate the NO/cyclic GMP pathway and inhibit both the phospholipase C gamma 2 (PLC gamma2)/protein kinase C (PKC) and PI3K/AKT-MAPK signaling pathways in activated platelets to inhibit platelet aggregation. In activated platelets, these three signaling pathways are downstream of integrin activation mediated by collagen binding and influence the association of fibrinogen with its receptors. Additionally, andrographolide may exert its anti-cancer activity through the induction of cell cycle arrest at G0/G1 phase and the stimulation of lymphocyte proliferation and activation. These processes could result in decreased proliferation of and increased immunocytotoxicity against tumor cells.
An opioid receptor agonist belonging to the piperidine class with analgesic activity. By binding to and activating opioid receptors in the central nervous sytem (CNS), anileridine mimics the endogenous opioids resulting in a decrease of nociceptve neurotransmitters and eventually an analgesic effect.
A synthetic indanedione anticoagulant. Anisindione interferes with the vitamin K-dependent hepatic synthesis of active clotting factors by inhibiting the reduction of vitamin K. This leads to an inhibition of gamma-carboxylation of glutamic acid residues to gamma-carboxyglutamic acid in clotting factors II, VII, IX and X. The consequential effects of this inhibition include a reduced activity of these clotting factors and prolonged blood clotting time.
An antineoplastic antibiotic that intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. Anthrapyrazoles may also block cell cycle division. In the presence of electron donors, some anthrapyrazole antibiotics cause single-strand breaks in DNA via photosensitization by visible light. These agents are less cardiotoxic than doxorubicin. (NCI04)
A piperidinedione antineoplaston with potential antineoplastic activity. Antineoplaston A10 was originally isolated from human urine but is now synthetically derived. This agent intercalates into DNA, resulting in cell cycle arrest in G1 phase, reduction of mitosis, and decreased protein synthesis. Antineoplaston A10 may also inhibit ras-oncogene expression and activate tumor suppressor gene p53, leading to cell differentiation and apoptosis. (NCI04)
A fungal toxin isolated from Arachniotus aureus with activity against RNA viruses such as poliovirus, coxsackie virus, and rhino- and parainfluenza viruses. Aranotin inhibits viral RNA synthesis by impeding the activity of RNA-dependent RNA polymerase.
The butyric acid salt of the amino acid arginine. In EBV-related lymphomas, arginine butyrate induces EBV thymidine kinase transcription and may act synergistically with the antiviral agent ganciclovir to inhibit cell proliferation and decrease cell viability. In addition, the butyrate moiety inhibits histone deacetylase, which results in hyperacetylation of histones H3 and H4. Acetylated histones have a reduced affinity for chromatin; this reduced histone-chromatin affinity may allow chromosomal unfolding, potentially enhancing the expression of genes related to tumor cell growth arrest and apoptosis. (NCI04)
A novel aryl diketone with activity against both DNA and RNA viruses. Arildone interacts directly with the poliovirus capsid and prevents uncoating in infected cells. It also inhibits herpes simplex virus type 2 protein synthesis and viral DNA replication by an unknown mechanism of action.
A small-molecule arsenic compound with antineoplastic activity. The mechanism of action of arsenic trioxide is not completely understood. This agent causes damage to or degradation of the promyelocytic leukemia protein/retinoic acid receptor-alpha (PML/RARa) fusion protein; induces apoptosis in acute promyelocytic leukemia (APL) cells and in many other tumor cell types; promotes cell differentiation and suppresses cell proliferation in many different tumor cell types; and is pro-angiogenic. (NCI04)
An artemisinin derivative that is used in the treatment of MALARIA.
A water-soluble, semi-synthetic derivative of the sesquiterpene lactone artemisinin with anti-malarial, anti-schistosomiasis, antiviral, and potential anti-neoplastic activities
Carotenoid having a chemical structure similar to beta-carotene with hydroxyl groups at the number 3 and 3' carbon atoms and carbonyl (C=O) functions at the number 4 and 4' carbon atoms.
A natural clay-like mineral mixture of hydrated aluminum silicate containing magnesium, adsorbent Attapulgite (kaopectate) acts locally in the intestines to adsorb bacteria and toxins; reduce water loss; and treat diarrhea. Sometimes it is activated by heat to increase absorbency. (NCI04)
An agonist of niacin receptors capable of mimicking niacin's ability to increase high-density lipoprotein (HDL). Acifran produces these effects at lower doses and without the skin flushing side-effects associated with niacin treatment.
A hydrazine compound that has been investigated for antineoplastic activity. (NCI04)
The triacetate salt of azauridine, a synthetic triazine nucleoside derivative possessing antineoplastic and anti-psoriatic activity. After metabolism to 6-azauridine-5-prime monophosphate, 6-Azauridine inhibits de novo pyrimidine biosynthesis and its 5-prime triphosphate metabolite gets incorporated into RNA, thereby preventing RNA synthesis.
A naturally occurring dicarboxylic acid produced by Malassezia furfur and found in whole grain cereals, rye, barley and animal products. Azelaic acid possesses antibacterial, keratolytic, comedolytic, and anti-oxidant activity. Azelaic acid is bactericidal against Proprionibacterium acnes and Staphylococcus epidermidis due to its inhibitory effect on the synthesis of microbial cellular proteins. Azelaic acid exerts its keratolytic and comedolytic effects by reducing the thickness of the stratum corneum and decreasing the number of keratohyalin granules by reducing the amount and distribution of filaggrin in epidermal layers. Azelaic acid also possesses a direct anti-inflammatory effect due to its scavenger activity of free oxygen radical. This drug is used topically to reduce inflammation associated with acne and rosacea.
A monosulfamyl belonging to the class of loop diuretics. Azosemide inhibits sodium and chloride reabsorption throughout the thick ascending limb of the loop of Henle.
An antineoplastic-antibiotic diazo analog of L-glutamine isolated from the bacterium Streptomyces ambofaciens. Azotomycin inhibits glutamine-dependent enzymes involved in purine and pyrimidine biosynthesis, resulting in inhibition of DNA synthesis. (NCI04)
A water-insoluble heterocyclic amide with potential antineoplastic activity. Daniquidone inhibits topoisomerases I and II, thereby inhibiting DNA replication and repair, and RNA and protein synthesis. The acetylated form of daniquidone is highly toxic and is capable of inducing unscheduled DNA synthesis; rapid acetylators are more likely to experience toxicity with this agent.
A pyrazolinone derivative with potential antimetastatic activities. Nafazatrom, originally developed as an antithrombotic agent, inhibits the key prostaglandin catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase, which prolongs the biological half-life of prostacyclin (prostaglandin I2; PGI2) and prevents intravascular coagulation. This agent also serves as a reducing cofactor with the hydroperoxidase moiety of cyclooxygenase and accelerates the conversion of arachidonic acid into precursors of PGI2. An elevated level of PGI2 prevents aggregation of platelets; subsequently it decreases the formation of tumor cell-platelet aggregates as well as their sequestration in blood vessels, which is an important initiating step in the development of metastasis.
A structural analog of clofibrate, converted to its free acid form after oral administration. Beclobrate reduces LDL-cholesterol and increased HDL-cholesterol and improves the clearance of triglyceride-rich lipoproteins by improving lipoprotein-lipase activity.
A carboxyl-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, benazepril is metabolized to its active form benazeprilat. Benazeprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II resulting in vasodilation. Benazeprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
An antilipidemic agent that decreases the relative rate of hepatic triacylglycerol synthesis. Benfluorex was never approved for use in the United States and was withdrawn in the European Union because of an increased risk of pulmonary hypertension and valvular disease.
The benzathine salt form of a semisynthetic beta-lactamase resistant penicillin antibiotic with antibacterial activity. Cloxacillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, thereby preventing the cross-linkage of peptidoglycans, which are critical components of the bacterial cell wall. This leads to a weakening of the bacterial cell wall, eventually causing bacterial cell lysis.
A synthetic antiparkinson tertiary amine structurally related to atropine, Benztropine Mesylate acts as a central muscarinic antagonist and inhibits dopamine uptake. With antihistaminic and local anesthetic properties as well, it is indicated for symptomatic relief of parkinsonism and drug-induced extrapyramidal reactions. (NCI04)
A fungistatic compound that is widely used as a food preservative. It is conjugated to GLYCINE in the liver and excreted as hippuric acid.
A synthetic butylamino-benzoate derivative related to tetracaine and a peripherally acting antitussive, nonnarcotic Benzonatate reduces the cough reflex by anesthetizing and depressing mechanoreceptors in the respiratory passages, lungs, and pleura. It is recommended for cough relief in the common cold, bronchitis, pneumonia, and for chronic cough such as in asthma. (NCI04)
A nitroimidazole derivative having an antiprotozoal activity by interfering with parasite protein biosynthesis, influencing cytokines production and stimulating host phagocytosis. (NCI)
An intermediate acting agent belonging to the class of thiazide diuretics. Benzthiazide, also known as benzothiazide, is no longer commercially available in the United States.
A microbial metabolite and dipeptide with potential immunomodulatory and antitumor activities. Ubenimex competitively inhibits many aminopeptidases, including B, N and leucine aminopeptidases. Aminopeptidases has been implicated in the process of cell adhesion and invasion of tumor cells. Therefore, inhibiting aminopeptidases may partially attribute to the antitumor effect of ubenimex. This agent also activates T lymphocyte, macrophage and bone marrow stem cell as well as stimulates release of interleukin-1 and -2, thus further enhances its antitumor activity.
A sulfamoylchlorobenzoic acid derivative with diuretic activity. Besulpamide appears to be similar in diuretic activity to that of chlorthalidone, clopamide and xipamide.
A thiopurine nucleoside derivative with antineoplastic activity. After conversion to the triphosphate, beta-thioguanine deoxyriboside is incorporated into DNA, resulting in inhibition of DNA replication. This agent is cytotoxic against leukemia cell lines and has demonstrated some activity against leukemia cells in vivo. Beta-thioguanine deoxyriboside demonstrates antineoplastic activity against 6-thioguanine-resistant tumor cells. (NCI04)
A carotenoid that is a precursor of VITAMIN A. Beta carotene is administered to reduce the severity of photosensitivity reactions in patients with erythropoietic protoporphyria (PORPHYRIA, ERYTHROPOIETIC).
A poorly soluble, ortho-naphthoquinone with potential antineoplastic and radiosensitizing activity. Beta-lapachone (b-lap) is bioactivated by NAD(P)H:quinone oxidoreductase-1 (NQO1), creating a futile oxidoreduction that generates high levels of superoxide. In turn, the highly reactive oxygen species (ROS) interact with DNA, thereby causing single-strand DNA breaks and calcium release from endoplasmic reticulum (ER) stores. Eventually, the extensive DNA damage causes hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme facilitating DNA repair, accompanied by rapid depletion of NAD+/ATP nucleotide levels. As a result, a caspase-independent and ER-stress induced mu-calpain-mediated cell death occurs in NQO1-overexpressing tumor cells. NQO1, a flavoprotein and two-electron oxidoreductase, is overexpressed in a variety of tumors.
A polycyclic aromatic hydrocarbon that consists of a flavone group attached to a benzene ring. Beta-naphthoflavone is an inducer of the hepatic cytochrome p450 CYP1A1 and CYP1A2.
The 17,21-dipropionate ester of betamethasone, a synthetic glucocorticoid with metabolic, immunosuppressive and anti-inflammatory actions. Betamethasone dipropionate binds to specific intracellular glucocorticoid receptors and subsequently binds to DNA to modify gene expression. The synthesis of certain anti-inflammatory proteins is induced while the synthesis of certain inflammatory mediators is inhibited. As a result, there is an overall reduction in chronic inflammation and autoimmune reactions.
A slowly hydrolyzing muscarinic agonist with no nicotinic effects. Bethanechol is generally used to increase smooth muscle tone, as in the GI tract following abdominal surgery or in urinary retention in the absence of obstruction. It may cause hypotension, HEART RATE changes, and BRONCHIAL SPASM.
A pentacyclic lupane-type triterpene derivative of betulin (isolated from the bark of Betula alba, the common white birch) with antiinflammatory, anti-HIV and antineoplastic activities. Betulinic acid induces apoptosis through induction of changes in mitochondrial membrane potential, production of reactive oxygen species, and opening of mitochondrial permeability transition pores, resulting in the release of mitochondrial apogenic factors, activation of caspases, and DNA fragmentation. Although originally thought to exhibit specific cytotoxicity against melanoma cells, this agent has been found to be cytotoxic against non-melanoma tumor cell types including neuroectodermal and brain tumor cells.
A fibrate derivative with antilipidemic activity. Binifibrate consists of two nicotinic radicals and one clofibiric radical esterified by a glycerol moiety.
An isoflavone found in soy products. Soy isoflavones (estrogen-like substances made by some plants) are being studied to see if they help prevent cancer.
An anthracenyl bishydrazone with antineoplastic activity. Bisantrene intercalates with and disrupts the configuration of DNA, resulting in DNA single-strand breaks, DNA-protein crosslinking, and inhibition of DNA replication. This agent is similar to doxorubicin in activity, but unlike doxorubicin, does not exhibit cardiotoxicity. (NCI04)
A bismuth salt of salicylic acid. Little absorbed from the gastrointestinal tract, bismuth subsalicylate exerts a local effect on the gastric mucosa, coating it and protecting it from the corrosive effects of acid and pepsin. This agent also has local antimicrobial properties. (NCI04)
A cardioselective beta-1 adrenergic blocker. It is effective in the management of HYPERTENSION and ANGINA PECTORIS.
A diester sympathomimetic amine with bronchodilator activity. As an ester prodrug, bitolterol is hydrolyzed by esterases to its active metabolite colterol (N-t-butylarterenol). Colterol selectively binds to and activates beta-2 adrenergic receptors in bronchiolar smooth muscle, thereby causing stimulation of adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased intracellular cAMP levels cause relaxation of bronchial smooth muscle. This increases air flow and prevents bronchospasms and may eventually lead to an improvement of airway function.
A serotonin antagonist having antiemetic properties.
A pyrimidinone derivative with anti-allergic activity. Pemirolast blocks the antigen-mediated calcium ion influx into mast cells. This prevents mast cell degranulation, resulting in mast cell stabilization and inhibition of the release of inflammatory mediators, such as histamine and leukotrienes, which are involved in the allergic process. Pemirolast also prevents inflammatory mediator release from eosinophils.
An orally available antimetabolite composed of the 1-ethoxymethyl derivative of 5-fluorouracil (5-FU) and the dihydropyrimidine dehydrogenase (DPYD) inhibitor 3-cyano-2,6-dihydroxypyridine (CNDP) in a 1:1 molar ratio, with antineoplastic activity. Upon administration, the prodrug emitefur is converted into 5-FU, while CNDP prevents the degradation of 5-FU by inhibiting DPYD and thereby prolonging the half-life of 5-FU. This increases 5-FU's concentration and thus its antitumor activity through inhibition of DNA and RNA synthesis, as well as inhibition of thymidylate synthase activity. In addition, by inhibiting the formation of 5-FU metabolites, some toxic effects associated with these metabolites may be reduced. DPYD is the rate-limiting enzyme in the catabolism of 5-FU.
A PEPTIDE that is secreted by the BRAIN and the HEART ATRIA, stored mainly in cardiac ventricular MYOCARDIUM. It can cause NATRIURESIS; DIURESIS; VASODILATION; and inhibits secretion of RENIN and ALDOSTERONE. It improves heart function. It contains 32 AMINO ACIDS.
A combination of the semisynthetic broad-spectrum antibiotic amoxicillin and the beta-lactamase enzyme inhibitor clavulanate potassium. Clavulanate potassium increases the serum half-life of amoxicillin by inhibiting beta-lactamase-mediated metabolism of amoxicillin. Amoxicillin inhibits bacterial cell wall synthesis by binding to penicillin binding proteins and inhibiting peptidoglycan synthesis, a critical component of bacterial cell walls.
A derivative of bromoacrylic acid with cytostatic and antineoplastic activity. Bromebric acid appears to inhibit purine synthesis, oxidative phosphorylation and DNA synthesis. This agent inhibits tumor cell growth and causes cell cycle arrest. This agent may also have some use in the phrophylaxis of migraine.
A nonsteroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory activities. Upon ophthalmic administration, bromfenac binds to and inhibits the activity of cyclooxygenase II (COX II), an enzyme which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins (PG). By inhibiting PG formation, bromfenac is able to inhibit PG-induced inflammation, thereby preventing vasodilation, leukocytosis, disruption of the blood-aqueous humor barrier, an increase in vascular permeability and an increase in intraocular pressure (IOP).
A brominated derivative of diphenhydramine, an ethanolamine derivative and histamine H1 receptor antagonist with anti-allergic, sedative, antiemetic and anticholinergic properties. Bromazine competitively and selectively blocks central and peripheral histamine H1 receptors, thereby alleviating the symptoms caused by endogenous histamine on bronchial, capillary and gastrointestinal (GI) smooth muscles. This prevents histamine-induced bronchoconstriction, vasodilation, increased capillary permeability, itching, and spasmodic contractions of GI smooth muscle. In addition, bromazine binds to and blocks peripheral and central muscarinic receptors.
An oral immunostimulant that causes the body to produce interferon and other substances.
A triazolo-benzodiazepine derivative with sedative, hypnotic, anxiolytic and anticonvulsant activities. Brotizolam binds to the benzodiazepine binding site on the gamma aminobutyric acid (GABA)-A receptor in the central nervous system (CNS). This leads to an increase in the opening of chloride channels, membrane hyperpolarization and increases the inhibitory effect of GABA on the CNS.
A triterpene quassinoid antineoplastic antibiotic isolated from the plant Brucea antidysenterica. Bruceantin inhibits the peptidyl transferase elongation reaction, resulting in decreased protein and DNA synthesis. Bruceantin also has antiamoebic and antimalarial activity. (NCI04)
A macrocyclic lactone isolated from the bryozoan Bugula neritina with antineoplastic activity. Bryostatin 1 binds to and inhibits the cell-signaling enzyme protein kinase C, resulting in the inhibition of tumor cell proliferation, the promotion of tumor cell differentiation, and the induction of tumor cell apoptosis. This agent may act synergistically with other chemotherapeutic agents. (NCI04)
A glucocorticoid used in the management of ASTHMA, the treatment of various skin disorders, and allergic RHINITIS.
An active ingredient and one of the glycosides in the traditional Chinese medicine ChanSu; it is also a bufadienolide toxin originally isolated from the venom of the Chinese toad Bufo gargarizans, with potential cardiotonic and antineoplastic activity. Although the mechanism of action of bufalin is still under investigation, this agent is a specific Na+/K+-ATPase inhibitor and can induce apoptosis in cancer cell lines through the activation of the transcription factor AP-1 via a mitogen activated protein kinase (MAPK) pathway.
A bufadienolide toxin originally isolated from the venom of the Chinese toad Bufo gargarizans; it is also one of the glycosides in the traditional Chinese medicine ChanSu, with potential cardiotonic activity. Although the mechanism of action of bufogenin is still under investigation, this agent is a specific Na+/K+-ATPase inhibitor and has been shown to reduce blood pressure in a rat model of preeclampsia.
A barbiturate that exerts its effect by mimicking the inhibitory effect of gamma-aminobutyric acid (GABA) by binding to a site, distinct from the benzodiazepine binding site, on the GABA receptor. This leads to an increase in the duration of GABA-mediated opening of chloride channels and enhances the inhibitory effect of GABA. Consequently, its physiologic effects include sedation, hypnosis, reduction of anxiety, and respiratory depression and the drug causes tolerance and dependence.
A flavonoid obtained from the seed of Cyclopia subternata. It is a specific protein tyrosine kinase inhibitor that induces apoptosis. (NCI)
A synthetic amino acid. Buthionine sulfoximine irreversibly inhibits gamma-glutamylcysteine synthase, thereby depleting cells of glutathione, a metabolite that plays a critical role in protecting cells against oxidative stress, and resulting in free radical-induced apoptosis. Elevated glutathione levels are associated with tumor cell resistance to alkylating agents and platinum compounds. By depleting cells of glutathione, this agent may enhance the in vitro and in vivo cytotoxicities of various chemotherapeutic agents in drug-resistant tumors. Buthionine sulfoximine may also exhibit antiangiogenesis activity. (NCI04)
A S-substituted analog of mercaptopurine and purine antagonist with cytostatic activity. Butocin inhibits purine nucleotide synthesis and DNA replication.
A synthetic imidazole derivative with fungistatic properties. Butoconazole interferes with steroid biosynthesis by inhibiting the conversion of lanosterol to ergosterol, thereby changing the fungal cell membrane lipid composition. This alters cell permeability and leads to growth inhibition. Butaconazole nitrate is active against many dermatophytes and yeasts. It also contains antibacterial effects against some gram-positive organisms.
An alpha-amino acid that is a derivative of alanine with a side chain that is one carbon longer than the alanine side chain. It is synthesized through the transamination of oxobutyrate and is utilized in the biosynthesis of nonribosomal peptides.
A synthetic antifolate agent with antiparasitic, antipsoriatic and antitumor properties. Piritrexim inhibits the enzyme dihydrofolate reductase enzyme, thereby disrupting folate metabolism and DNA synthesis and cell division. (NCI04)
A synthetic alkylamine with non-sedative antihistaminergic activity. Acrivastine competitively blocks the histamine H1 receptor and limits the typical allergic and anaphylactic responses, including bronchoconstriction, vasodilation, increased capillary permeability, and spasmodic contraction of gastrointestinal smooth muscle, caused by actions of histamine on bronchial, and gastrointestinal smooth muscles, and on capillaries. This drug also prevents histamine-induced pain and itching of the skin and mucous membranes. (NCI05)
A hydrolyzable tannin with a propenoic acid (COOHCH=CH-), and hydroxyl groups at the 3 and 4 positions of the phenyl ring. The chemical structure is C1=CC(=C(C=C1\C=C\C(=O)O)O)O.
The phenethyl alcohol ester of caffeic acid and a bioactive component of honeybee hive propolis, with antineoplastic, cytoprotective and immunomodulating activities. Upon administration, caffeic acid phenethyl ester (CAPE) inhibits the activation of nuclear transcription factor NF-kappa B and may suppress p70S6K and Akt-driven signaling pathways. In addition, CAPE inhibits PDGF-induced proliferation of vascular smooth muscle cells through the activation of p38 mitogen-activated protein kinase (MAPK) and hypoxia-inducible factor (HIF)-1alpha and subsequent induction of heme oxygenase-1 (HO-1).
Commercial citrate of caffeine, though not a definite salt. It is the alkaloid caffeine, with a portion of adherent citric acid, as indicated by its pharmacopoeial name (citrated caffeine). Its general action and uses are the same as those given under caffeine. Caffeine citrate is used chiefly as a remedy for the idiopathic headache (migraine). This salt is very soluble in water, and is assimilated much more readily than pure caffeine when taken into the stomach. (NCI04)
The calcium salt form of heparin. As a glycosaminoglycan anticoagulant, heparin calcium binds to antithrombin III to form a heparin-antithrombin III complex. The complex binds to and irreversibly inactivates thrombin and other activated clotting factors IX, X, XI, and XII and prevents the transformation of fibrinogen to fibrin. (NCI)
A loosely cross-linked synthetic polycarboxylic-type hydrophilic polymer resin, laxative and anti-diarrheal Calcium Polycarbophil increases stool frequency, fecal water content, and fecal weight in a dose-dependent manner. It is used for idiopathic constipation, secretory diarrhea, and irritable bowel syndrome. (NCI04)
A saturated medium-chain fatty acid with an 8-carbon backbone. Octanoic acid is found naturally in the milk of various mammals and is a minor component of coconut oil and palm kernel oil.
An agent derived from acetohydroxamic acid with potential antineoplastic activity. Caracemide inhibits ribonuclease reductase, resulting in decreased DNA synthesis and tumor growth; it also inhibits acetylcholinesterase. In vivo, caracemide contributes to the formation of the neurotoxin methyl isocyanate; this effect, along with the agent's acetylcholinesterase activity, may be responsible for the severe central nervous system toxicity observed in clinical trials. (NCI04)
methylene (:CH2) and related compounds containing a carbon atom with 2 unpaired electrons; i.e., a diradical.
An inhalant consisting of hyperoxic gas (95%-98% oxygen and 2%-5% carbon dioxide) with radiosensitizing properties. Inhaled carbogen reduces diffusion-limited tumor hypoxia, increasing tumor radiosensitivity due to the increased availability of molecular oxygen for cytotoxic radiation-induced oxygen free radical production. (NCI04)
The tromethamine salt of the (15S)-15 methyl analogue of naturally occurring prostaglandin F2 alpha (PGF2 alpha) with oxytocic activity. Mimicking endogenous PGF2 alpha, carboprost activates prostaglandin F receptor, a G-protein coupled receptor, on smooth muscle cells, thereby resulting in smooth muscle contractions. When administered intramuscularly on gravid subjects, this agent induces myometrium contractions, thereby initiating luteolysis and consequently parturition. Furthermore, carboprost's action on vascular smooth muscle and gastrointestinal tract sphincters leads to raised blood pressure and induces vomiting or diarrhea, respectively.
A nucleoside reverse transcriptase inhibitor analog of guanosine. Carbovir decreases HIV viral loads, retards or prevents the damage to the immune system, and reduces the risk of developing AIDS.
A second-generation platinum analog with potential antineoplastic activity. Dacplatinum alkylates DNA at the N-7 position of guanine, thereby producing DNA interstrand crosslinks and DNA strand breaks, and inhibiting DNA replication. (NCI04)
A propionic acid derivate and nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic activities, used exclusively in veterinary medicine. Carprofen inhibits the activity of the enzymes cyclo-oxygenase (COX) I and II, resulting in a decreased formation of precursors of prostaglandins and thromboxanes. This inhibits the formation of prostaglandins, by prostaglandin synthase, that are involved in pain, inflammation and fever. Ibuprofen also causes a decrease in the formation of thromboxane A2 synthesis, by thromboxane synthase, thereby inhibiting platelet aggregation.
A carbazole and propanol derivative that acts as a non-cardioselective beta blocker and vasodilator. It has blocking activity for ALPHA 1 ADRENERGIC RECEPTORS and, at higher doses, may function as a blocker of CALCIUM CHANNELS; it also has antioxidant properties. Carvedilol is used in the treatment of HYPERTENSION; ANGINA PECTORIS; and HEART FAILURE. It can also reduce the risk of death following MYOCARDIAL INFARCTION.
1,6,7,8-tetrahydroxy octahydroindolizine; an inhibitor of glucosylceramidase used to block certain protein glycosylations.
A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made.
A semisynthetic first-generation cephalosporin with antibacterial activity. Cefazaflur binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
A third-generation, semi-synthetic, beta-lactam cephalosporin antibiotic with antibacterial activity. Cefpiramide binds to penicillin-binding proteins (PBPs), transpeptidases that are responsible for crosslinking of peptidoglycan. By preventing crosslinking of peptidoglycan, cell wall integrity is lost and cell wall synthesis is halted.
A cardioselective beta-1 adrenergic antagonist that has intrinsic symopathomimetic activity. It is used in the management of ANGINA PECTORIS and HYPERTENSION.
An antineoplastic protein isolated from the seeds of the plant Caesalpinia gilliesii with antineoplastic activity. Cesalin intercalates into and crosslinks DNA and inhibits the incorporation of the nucleotides uridine and thymidine into DNA, thereby inhibiting DNA and protein synthesis. (NCI04)
A unique, PPARalpha-independent peroxisome proliferator with hypolipidemic activity. Cetaben decreases serum cholesterol levels by inhibiting cholesterol biosynthesis.
A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects.
Cetyltrimethylammonium compound whose salts and derivatives are used primarily as topical antiseptics.
A water-soluble nitrosourea that cross-links with DNA, causing inhibition of DNA synthesis.
A long-acting, small polar angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Libenzapril competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Libenzapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A quassinoid phytochemical isolated from Ailanthus integrifolia sp. calycina and other plant species with potential antineoplastic activity. Chaparrinone inhibits protein synthesis, has antimalarial properties, and is cytotoxic to some tumor cells. (NCI04)
A triazine derivative and diuretic agent. Chlorazanil appears to prevent the absorption of sodium and chloride in the distal convoluted tubule.
The gluconate salt form of chlorhexidine, a biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine gluconate is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, chlorhexidine gluconate penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram positive bacteria are more negatively charged, they are more sensitive to this agent.
The chloride salt form of acetylcholine, a synthetic, quaternary amino alcohol with cholinergic properties. Acetylcholine chloride mimics the parasympathomimetic effect of the endogenous compound acetylcholine. Administered as an ophthalmic solution, this drug stimulates the cholinoceptors in the sphincter muscle of the iris, causing the pupil to constrict. (NCI05)
A rhodamine-based dye used as a photosensitizing agent in cytotoxic photodynamic therapy. (NCI)
The phosphate salt of chloroquine, a quinoline compound with antimalarial and anti-inflammatory properties. Chloroquine is the most widely used drug against malaria, except for those cases caused by chloroquine resistant Plasmodium falciparum. Although the mechanism of action is not fully understood, chloroquine is shown to inhibit the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. Chloroquine may also interfere with the biosynthesis of nucleic acids.
A synthetic quinoline derivative with antibacterial activity. Although the mechanism of action is not fully understood, topical administration of chloroxine diminishes mitotic activity in the epidermis, thereby reducing excessive scaling associated with dandruff or seborrheic dermatitis of the scalp, including psoriasis and eczema.
A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion.
The choline salt of theophylline with an anti-asthmatic property. Oxtriphylline appears to inhibit phosphodiesterase and prostaglandin production, regulates calcium flux and intracellular calcium distribution, and antagonizes adenosine. Physiologically, this agent causes relaxation of bronchial smooth muscle, produces vasodilation (except in cerebral vessels), stimulates cardiac muscle, as well as induces diuresis and gastric acid secretion. It may also suppress inflammation and improve contractility of the diaphragm.
A synthetic derivative of acridine carboxamide with antineoplastic properties. CI-921, a lipophilic and water-soluble analog of amsacrine, inhibits the enzyme topoisomerase ll, thereby blocking DNA replication and RNA and protein synthesis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38943&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38943&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1050"" NCI Thesaurus)
A cyclohexane and pyridinone derivative that is used for the treatment of fungal infections of the skin and nails, and for treatment of VAGINAL YEAST INFECTIONS.
A broad spectrum antiviral agent with a largely non-specific and complex mode of antiviral action. Cicloxolone has been shown to impair Golgi apparatus functions related to transport of glycoproteins of vesicular stomatitis virus.
An agent belonging to the glitazone (thiazolidinedione) class of antidiabetic agents with antihyperglycemic activity. Ciglitazone also exerts anti-inflammatory activity through the modulation of nuclear factor-kappaB-mediated pathways. In addition, this agent inhibits angiogenesis by reducing vascular endothelial growth factor (VEGF) production and inhibits growth of melanoma cells by inhibiting the expression of (C-X-C motif) ligand 1 (CXCL1). This agent is the prototypical compound for the thiazolidinedione class, and has never been marketed.
One of the ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACE inhibitors) used for hypertension. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat.
The active metabolite of cilazapril, a pyridazine angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, cilazapril is rapidly metabolized in the liver to cilazaprilat; cilazaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II, resulting in vasodilation. Cilazaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A narrow-spectrum cyclic lipopeptide derivative of echinocandin B derived from Aspergillus with fungicidal activity.
A quinoline and tetrazole derivative that acts as a phosphodiesterase type 3 inhibitor, with anti-platelet and vasodilating activity. It is used in the treatment of PERIPHERAL VASCULAR DISEASES; ISCHEMIC HEART DISEASE; and in the prevention of stroke.
A choleretic agent. Cinametic acid relaxes the sphincter of Oddi and regulates hepato-biliary function. In addition, this agent is used in liver function tests.
A monoterpene and cyclohexanol derivative that is the major component of EUCALYPTUS OIL. It is used in mouthwash, insect repellent, and as a cough suppressant, and also is widely used as a flavoring agent and solvent. It has antimicrobial properties.
A bufadienolide compound extracted from the dried venom secreted by the parotid glands of toads and one of the glycosides in the traditional Chinese medicine ChanSu, with potential antineoplastic activity. Although the mechanism of action of cinobufagin is still under investigation, it has been found to suppress cancer cell proliferation and cause apoptosis in cancer cells via a sequence of apoptotic modulators that include mitochondrial Bax and cytosolic chromosome c, and caspases 3, 8, and 9. Possible upstream mediators of cinobufagin-induced apoptosis include Fas and p53.
A fibrate derivative with antilipidemic activity.
A solution of citric acid, sodium citrate, monobasic sodium phosphate, and dextrose in water used as an anticoagulant in the collection and preservation of whole blood.
A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability.
A third-generation, water-soluble platinum compound. (NCI)
A fibrate derivative with antilipidemic activity. Climofibrate has its greatest effect in reducing VLDL-triglyceride levels.
A 1,5-benzodiazepine and partial gamma-aminobutyric acid (GABA) receptor agonist, with anxiolytic, sedative, and anticonvulsant activities. Clobazam binds to a specific site, distinct from the inhibitory neurotransmitter GABA binding site, on the benzodiazepine-GABA-A-chloride ionophore receptor complex located in the central nervous system (CNS). This binding causes an allosteric modification of the receptor and enhances the affinity of GABA to the receptor leading to an increase in the opening of chloride-channels. This leads to an increase in chloride ion conductance, neuronal hyperpolarization, inhibition of the action potential and a decrease in neuronal excitability.
The propionate salt form of clobetasol, a topical synthetic corticosteroid with anti-inflammatory, anti-pruritic, and vasoconstrictive properties. Clobetasol propionate exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators. Specifically, clobetasol propionate appears to induce phospholipase A2 inhibitory proteins, thereby controlling the release of the inflammatory precursor arachidonic acid from membrane phospholipids by phospholipase A2.
A glucocorticoid receptor agonist with metabolic, anti-inflammatory, and immunosuppressive activity. Clocortolone pivalate exerts its effect by interacting with specific intracellular receptors and subsequently binds to DNA to modify gene expression. This results in an induction of the synthesis of certain anti-inflammatory proteins while inhibiting the synthesis of certain inflammatory mediators. Consequently, an overall reduction in chronic inflammation and autoimmune reactions are accomplished.
A topical imidazole antifugal agent with activity against Candida albicans.
A derivative of clofibrate. In the body clofibride is converted into 4-chlorophenoxyisobutyric acid (CPIB) and 4-hydroxy-N-dimethylbutyramide (HMB).
A synthetic, carbanilide compound with antiseptic activity. Cloflucarban is used as disinfectant and is found in antimicrobial soaps and deodorants.
The 2-chloroethyl ester of (methylsulfonyl) methanesulfonic acid with potential antineoplastic effects. Acting as a chloroethylating agent, clomesone induces the formation of DNA interstrand crosslinks in some cell lines, and exhibits antitumor activity in some animal models. Alkylating agents exert cytotoxic and, in some cases, chemotherapeutic effects by transferring alkyl groups to DNA, thereby damaging DNA and interfering with DNA synthesis and cell division. (NCI04)
A sulfonamide-based diuretic with thiazide-like activity. Cloreloxone has actions similar to that of thiazide diuretics.
A substance found in certain plants, including blessed thistle. It has been used in some cultures to treat certain medical problems. It may have anti-inflammatory and anticancer effects. Cnicin is a type of sesquiterpene lactone.
A reddish, toxic, metallic salt. Cobalt sulfate is used in the electrochemical industries, as a drier in paints and inks, as a coloring agent, in storage batteries and as a supplement for Vitamin B12 deficiency. Exposure to cobalt sulfate results in irritation of the skin, eyes and respiratory tract and affects the thyroid, lungs, heart and kidneys. Cobalt sulfate is mutagenic in mammalian cells and is reasonably anticipated to be a human carcinogen based on evidence of carcinogenicity in experimental animals. (NCI05)
Oil derived from fruits of the coconut plant, COCOS NUCIFERA.
A naturally occurring benzoquinone important in electron transport in mitochondrial membranes. Coenzyme Q10 functions as an endogenous antioxidant; deficiencies of this enzyme have been observed in patients with many different types of cancer and limited studies have suggested that coenzyme Q10 may induce tumor regression in patients with breast cancer. This agent may have immunostimulatory effects. (NCI04)
A stilbenoid phenol, originally isolated from the bark of the African bush willow tree Combretum caffrum, with vascular disrupting and antineoplastic activities. Combretastatin targets and binds to the colchicine-binding site of tubulin, thereby impairs the polymerization of tubulin dimers and prevents the formation of microtubules in the endothelial cells of tumor. As a result, this may eventually lead to a destruction of the tumor vasculature, disruption of tumor blood flow and tumor cell necrosis.
A water-soluble prodrug derived from the African bush willow (Combretum caffrum) with antineoplastic activity. Fosbretabulin is dephosphorylated to its active metabolite, combretastatin A4, which binds to tubulin and inhibits microtubule polymerization, resulting in mitotic arrest and apoptosis in endothelial cells. As apoptotic endothelial cells detach from their substrata, tumor blood vessels collapse; the acute disruption of tumor blood flow may result in tumor necrosis.
An HMG-CoA reductase inhibitor that was initially isolated from the mold Pythium ultimum. Mevastatin was the first statin to enter clinical trials.
A synthetic polymer (copolymer of 1,3-bis(methylaminocarboxyl)-2-methylenepropanecarbamate and N-vinyl pyrrolidone) of low molecular weight which acts as a nonspecific immune modulator and has been shown to have significant antitumor activity in vitro and in vivo in preclinical and some early clinical studies. The mechanism of action is unknown. Immunologic evaluation revealed some improvement in helper and suppressor T cell ratio, in vitro cytotoxicity tests, and lymphocyte blastogenic response. (NCI)
A sulfate salt of copper. It is a potent emetic and is used as an antidote for poisoning by phosphorus. It also can be used to prevent the growth of algae.
A purine nucleoside antimetabolite and antibiotic isolated from the fungus Cordyceps militaris with potential antineoplastic activity. Cordycepin is an adenosine analogue, which is readily phosphorylated to its mono-, di-, and triphosphate intracellularly. Triphosphate cordycepin can be incorporated into RNA, and inhibits transcription elongation and RNA synthesis due to the absence of a hydroxyl moiety at the 3' position. Because it can be converted to an inactive metabolite by adenosine deaminase, this agent must be administered with an adenosine deaminase inhibitor in order to be effective. Cordycepin has displayed cytotoxicity against some leukemic cell lines in vitro.
The synthetic hemisuccinate salt form of hydrocortisone, a corticosteroid with anti-inflammatory and immunosuppressive properties. Hydrocortisone acetate initially binds to the cytoplasmic glucocorticoid receptor; then the receptor-ligand complex is translocated to the nucleus where it initiates the transcription of genes encoding for anti-inflammatory mediators, such as cytokines and lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes.
The acetate ester of cortisone that is used mainly for replacement therapy in adrenocortical insufficiency and in the treatment of many allergic and inflammatory disorders.
The acetic acid ester of metacresol, an agent with antiseptic and analgesic properties. m-Cresyl acetate is used in an otic solution to treat bacterial and fungal infections of the outer ear, and in endodontic procedures.
A white, crystalline aromatic amine that is soluble in organic solvents and emits toxic fumes of nitrogen oxides when heated to decomposition. p-Cresidine is exclusively used as a chemical intermediate in the manufacture of dyes. p-Cresidine is reasonably anticipated to be a human carcinogen based on evidence of carcinogenicity in experimental animals. (NCI05)
A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)
Isotonic solutions of mineral salts, such as RINGER'S LACTATE and SODIUM CHLORIDE (SALINE SOLUTION), used in FLUID THERAPY to rehydrate BLOOD VOLUME.
A water-soluble nitrosoureido sugar derived from acosamine, with alkylating activity. Ecomustine alkylates and crosslinks DNA, thereby inhibiting replication and transcription and eventually resulting in a reduction of cellular proliferation.
An anthocyanidin with hydroxyl groups at C-3, -5, -7, -3', and -4'.
A dihydropyridine derivative with diuretic and antihypertensive activity. Cicletanine exerts thiazide-like diuretic activity. In addition, this agent inhibits protein kinase C (PKC) and is able to reverse vasoconstriction through the inhibition of PKC-mediated inhibition of Na/K-ATPase phosphorylation.
A centrally acting skeletal muscle relaxant with antidepressant activity. The exact mechanism of action of cyclobenzaprine has not been fully determined, but this drug seems to primarily act at the brain stem to reduce tonic somatic motor activity, influencing both gamma and alpha motor neurons leading to a reduction in muscle spasms.
A cyclic sulfonate ester with potential antineoplastic activity. As an alkylating agent, clyclodisone induces the formation of DNA interstrand crosslinks, DNA strand breaks, and alkali-labile lesions in the DNA of some tumor cell lines. Alkylating agents exert cytotoxic and chemotherapeutic effects by transferring alkyl groups to DNA, thereby damaging DNA and interfering with DNA synthesis and cell division. (NCI04)
A benzothiadiazide belonging to the class of thiazide diuretics. Cyclothiazide is indicated as adjunctive therapy in edema and in the treatment of hypertension. In addition, this agent is capable of inhibiting rapid desensitization of the ionotropic alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors, thereby potentiating glutamate responses which may induce seizures activity. Cyclothiazide was also found to inhibit gamma-aminobutyric acid (GABA)-A receptors.
An agent with anti-androgen and progestational properties. It shows competitive binding with dihydrotestosterone at androgen receptor sites.
An isoflavone extract from soy, which is an inactive analog of the tyrosine kinase inhibitor genistein. It has antioxidant and phytoestrogenic properties. (NCI)
A reddish, synthetic anthraquinone derivative. Danthron has been widely used as a laxative, but is no longer used to treat constipation and is currently used as an antioxidant in synthetic lubricants, in the synthesis of experimental antitumor agents, as a fungicide and as an intermediate for making dyes. This substance is a suspected mutagen and is reasonably anticipated to be a human carcinogen based on evidence of carcinogenicity in experimental animals. (NCI05)
A lipid soluble fluorochrome dye that binds to adenine-thymine (A-T) rich regions in DNA and, to a lesser extent, RNA. During fluorescence microscopy and flow cytometry, this agent binds to and detects endogenous and exogenous DNA in cellular samples. DAPI is excited with ultraviolet (UV) light (maximum absorption at 358 nm) and upon binding, emits light in the blue portion of the spectrum (461 nm for DNA and ~500 nm for RNA).
A complex comprised of Daunorubicin linked to DNA to enhance the topoisomerase II-mediated interaction with the DNA base pairs and reduce cardiotoxicity associated with anthracyclines. (NCI)
A saturated medium-chain fatty acid with a 10-carbon backbone. Capric acid is found naturally in the coconut and palm kernel oils as well as the milk of various mammals.
Highly conserved cysteine-rich peptides that play a role in host defense, and may be produced in response to microbial products or proinflammatory cytokines. Defensins bind to microbial cell membranes and can become aggregate either to form pore-like structures or to encapsulate the microbe. These peptide aggregates lead to destabilization of the cell membrane and, subsequently, to lysis of the microbe.
A polydeoxyribonucleotide with antithrombotic, thrombolytic, and fibrinolytic properties. Defibrotide induces the release of prostaglandin 12 and reduces the expression of adhesion molecules on endothelial cells, thereby interfering with platelet and leukocyte adhesion to the endothelium. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43522&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43522&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1064"" NCI Thesaurus)
The circulating form of a major C19 steroid produced primarily by the ADRENAL CORTEX. DHEA sulfate serves as a precursor for TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE.
A lipophilic, non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, delapril is converted to two active metabolites, delapril diacid and 5-hydroxy delapril diacid, which competitively bind to and inhibit ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Delapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
An analogue of tetrahydrocannabinol (THC) with antiemetic, anxiolytic, appetite-stimulating, analgesic, and neuroprotective properties. Delta-8-tetrahydrocannabinol (delta-8-THC) binds to the cannabinoid G-protein coupled receptor CB1, located in the central nervous system; CB1 receptor activation inhibits adenyl cyclase, increases mitogen-activated protein kinase activities, modulates several potassium channel conductances and inhibits N- and P/Q-type Ca2+ channels. This agent exhibits a lower psychotropic potency than delta-9-tetrahydrocannabinol (delta-9-THC), the primary form of THC found in cannabis.
The bromide salt form of demecarium, a quaternary ammonium compound and a long-acting cholinesterase inhibitor with parasympathomimetic activity. When used topically, demecarium inactivates both pseudocholinesterase and acetylcholinesterase, thereby preventing acetylcholine breakdown and increasing acetylcholine activity. This causes contraction of the iris sphincter muscle (producing miosis) and the ciliary muscle (affecting the accommodation reflex). In so doing, this agent increases the outflow of the aqueous humor, thereby reducing intraocular pressure.
A radiosensitizer that targets hypoxic cells and act as oxygen substitute making tumor cells sensitive to radiation damage.
A synthetic progestational hormone used often as the progestogenic component of combined oral contraceptive agents.
The acetate salt form of Dexamethasone, a synthetic adrenal corticosteroid with potent anti-inflammatory properties. In addition to binding to specific nuclear steroid receptors, dexamethasone also interferes with NF-kB activation and apoptotic pathways. This agent lacks the salt-retaining properties of other related adrenal hormones. (NCI04)
An alkylamine derivative with anticholinergic and sedative properties. Dexbrompheniramine is a histamine H1-receptor antagonist that competes with histamine for the H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels and respiratory tract. The antagonistic action of this agent blocks the activities of endogenous histamine, which subsequently leads to temporary relief from the negative histamine-mediated symptoms of allergic reaction such as bronchoconstriction, vasodilation, increased capillary permeability and spasmodic contractions of gastrointestinal smooth muscle.
An alkylamine, and first-generation histamine antagonist with anti-allergic activity. Dexchlorpheniramine competitively blocks H1 receptors, thereby preventing the actions of histamine on bronchial smooth muscle, capillaries and gastrointestinal (GI) smooth muscle. The antagonistic action of this agent blocks the activities of endogenous histamine, thereby preventing histamine-induced bronchoconstriction, vasodilation, increased capillary permeability, and GI smooth muscle spasms.
An alcoholic analogue of D-pantothenic acid and cholinergic agent. Dexpanthenol acts as a precursor of coenzyme A necessary for acetylation reactions and is involved in the synthesis of acetylcholine. Although the exact mechanism of the actions of dexpanthenol is unclear, it may enhance the effect of acetylcholine. Dexpanthenol acts on the gastrointestinal tract and increases lower intestinal motility. It is also applied topically to the skin to relieve itching and to promote healing.
A colorless, odorless, combustible aromatic amine that emits toxic fumes of nitrogen oxides when heated to decomposition. 4,4'-Oxydianiline is used in industry in the manufacture of polyimide and polyester resins. Exposure to this substance is irritating to the eyes, skin and respiratory-tract. 4,4'-Oxydianiline is reasonably anticipated to be a human carcinogen. (NCI05)
A trichothecene mycotoxin and potent teratogen. Anguidine inhibits initiation of protein synthesis, resulting in the death of rapidly proliferating cells. Anguidine also has been shown to both potentiate and protect against the cytotoxic effects of other drugs. (NCI04)
An allyl-S compound with the structure C=CCSSCC=C.
An allyl-S compound with the structure C=CCSSSCC=C.
A triazine derivative with antineoplastic activity. Dichloroallyl lawsone inhibits mitochondrial dihydroorotate dehydrogenase (DHOD), an enzyme that catalyzes the only redox step in de novo pyrimidine biosynthesis, and nucleotide (RNA and DNA) biosynthesis. (NCI04)
A synthetic second-generation platinum-containing compound related to cisplatin. Iproplatin binds to and forms DNA crosslinks and platinum-DNA adducts, resulting in DNA replication failure and cell death. Although less prone to glutathione inactivation compared to cisplatin, resistance to this agent has been observed in vitro due to repair of platination damage by tumor cells. (NCI04)
An inhibitor of anion conductance including band 3-mediated anion transport.
An orally-active, semisynthetic, fourth generation, nonethinylated progestogen with antiproliferative, antiandrogenic, anti-inflammatory and antiangiogenic activities that is used in hormone therapy and as a female contraceptive. Upon oral administration, dienogest binds intracellular progesterone receptors which then translocate to the nucleus where the drug-receptor complex interacts with progesterone response elements, thus altering the expression of target genes. Dienogest reduces the production of estradiol, prevents ovulation and alters the cervical mucus and endometrium. In addition, dienogest appears to suppress the expression of cell cycle regulator cyclin D1. Altogether, this may prevent the growth of endometrial epithelial cells and may reduce symptoms associated with leiomyoma.
A titanium metal complex, coordinated with asymmetric beta-diketonate ligands, with antineoplastic activity. Although the exact mechanism of action remains to be elucidated, budotitane potentially binds either to macromolecules via coordinative covalent bonds, or via intercalation between nucleic acids strands by the aromatic ring of the beta-diketonate. In addition, this agent appears to cause cardiac arrhythmias and is toxic to the liver and kidneys at higher doses. The development of budotitane was halted due to the rapid loss of its labile groups under physiological conditions.
The dipropionate ester of a synthetic, nonsteroidal form of estrogen. A well-known teratogen and carcinogen, diethylstilbestrol inhibits the hypothalamic-pituitary-gonadal axis, thereby blocking the testicular synthesis of testosterone, lowering plasma testosterone, and inducing a chemical castration.
A phenylpiperidine with antidiarrheal activity and an active metabolite of diphenoxylate. Difenoxin is chemically related to the narcotic opioid meperidine. Difenoxin acts primarily on the gastrointestinal wall by binding to opioid receptors on acetylcholine-containing nerves and inhibiting the release of acetylcholine from presynaptic nerve terminals. This leads to a reduction in intestinal motility. Difenoxin hydrochloride also mimics the action of endogenous opioid peptides at the CNS opioid receptors, (primarily mu-receptors), thereby inducing CNS effects.
The acetate salt form of diflorasone, a synthetic glucocorticoid with anti-inflammatory and immunosuppressive properties. Like other glucocorticoids, diflorasone enters the cell by diffusion across the cell membrane and binds to the glucocorticoid receptor (GR) in the cytoplasm. The receptor complex subsequently translocates to the nucleus and activates or represses genes by interacting with short, palindromic DNA sequences called glucocorticoid response element (GRE). Gene activation leads to the exertion of anti-inflammatory effects, e.g. upregulation of IkappaB, while gene repression inhibits production of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-2 and IL-6, thereby preventing activation of cytotoxic T-lymphocytes.
A glycoside compound, extracted from the leaves and seeds of the common foxglove, with anti-arrhythmic property. Digitalin inhibits the enzymatic activity of the sodium-potassium ATPase pump in cardiac tissue, thereby increasing intracellular sodium and calcium levels and providing a positive inotropic effect. This results in increased force of myocardial muscle contraction. This agent also has a vagal effect on the parasympathetic nervous system, and as such slows the ventricular heart rate as well as helps eliminate fluid from body tissues.
A combustible, yellowish liquid with a slight phenolic odor. Diglycidyl resorcinol ether is used as a liquid spray epoxy resin and in the production of other epoxy resins. Exposure to this substance irritates the eyes, skin and respiratory tract and adversely affects the immune system, central nervous system, liver and gastrointestinal tract. This substance is reasonably anticipated to be a human carcinogen based on evidence of carcinogenicity in experimental animals. (NCI05)
The purified component of HEMATOPORPHYRIN DERIVATIVE, it consists of a mixture of oligomeric porphyrins. It is used in photodynamic therapy (HEMATOPORPHYRIN PHOTORADIATION); to treat malignant lesions with visible light and experimentally as an antiviral agent. It is the first drug to be approved in the use of PHOTODYNAMIC THERAPY in the United States.
Capsaicinoid compound with side chain CO(CH2)6CH(CH3)2. The chemical structure is CC(C)CCCCCCC(=O)NCC1=CC(=C(C=C1)O)OC.
A histamine H2 receptor agonist that is often used to study the activity of histamine and its receptors.
A fumarate derivative that is used as a DERMATOLOGIC AGENT in the treatment of PSORIASIS and SKIN DISEASES. It also may be used as an IMMUNOSUPPRESSIVE AGENT in the treatment of MULTIPLE SCLEROSIS.
A colorless liquid that is rapidly hydrolyzed in water. Dimethylcarbamoyl chloride is used as a chemical intermediate in the production of pharmaceuticals, pesticides and dyes. Exposure to this substance results in eye irritation, damaged mucous membranes of the nose, throat, and lungs and causes liver disturbance. Dimethylcarbamoyl chloride is reasonably anticipated to be a human carcinogen based on evidence of carcinogenicity in experimental animals. (NCI05)
An aliphatic analogue of busulfan with potential antineoplastic activity. As an alkylating agent, dimethylbusulfan induces neutropenia and has been shown to exhibit antitumor effects in some animal models. Alkylating agents exert cytotoxic and chemotherapeutic effects by transferring alkyl groups to DNA, thereby damaging DNA and interfering with DNA synthesis and cell division. (NCI04)
A synthetic analogue of the naturally occurring prostaglandin F2 alpha. Prostaglandin F2 alpha stimulates myometrial activity, relaxes the cervix, inhibits corpus luteal steroidogenesis, and induces luteolysis by direct action on the corpus luteum. (NCI04)
A synthetic, potent allergic contact sensitizer with potential immunostimulatory activity. After sensitization process by repeated topical application of diphencyprone to a specific area, further application of this agent to the affected area may stimulate an immune response and may potentially be useful to clear the affected area from infection or cancer.
An ester prodrug of epinephrine, with sympathomimetic activity. Due to its lipophilicity, dipivefrin penetrates more easily to the anterior chamber of the eye and is hydrolyzed to epinephrine, when applied locally. Epinephrine, an adrenergic agonist, enhances the outflow of aqueous humor and decreases the production of aqueous humor by vasoconstriction. The overall result is a reduction in intraocular pressure.
A Benzidine-based azo dye that is metabolized to free Benzidine in vivo. Direct blue 6 is primarily used for the dyeing of textiles, leather and paper. Benzidine and its metabolic derivatives have been detected in the urine of workers exposed to Benzidine-based dyes. Exposure to this dye is strongly associated with the occurrence of bladder cancer. (NCI05)
A Benzidine-based azo dye that is metabolized to free Benzidine in vivo. Direct brown 95 is primarily used for the dyeing of textiles, leather and paper. Benzidine and its metabolic derivatives have been detected in the urine of workers exposed to direct Benzidine-based dyes and exposure is strongly associated with the occurrence of bladder cancer. (NCI05)
A compound with activity against human picornaviruses. Disoxaril binds to the hydrophobic pocket within the viral VP1 capsid protein and prevents structural transitions required for viral uncoating resulting in an inhibition of viral reproduction.
A synthetic partial beta-adrenergic agonist with sympathomimetic activity. Doxaminol may bind to and stimulate beta-1-adrenergic receptors located in the myocardium. As a result, it leads to a positive inotropic effect and increases in cardiac output.
A complex comprised of Doxorubicin linked to DNA to enhance the topoisomerase II-mediated interaction with the DNA base pairs and reduce cardiotoxicity associated with anthracyclines. (NCI)
A pyridine derivate histamine H1 antagonist with pronounced sedative properties. Doxylamine succinate competitively blocks the histamine H1 receptor and limits the typical allergic and anaphylactic responses, including bronchoconstriction, vasodilation, increased capillary permeability, and spasmodic contraction of gastrointestinal smooth muscle, caused by actions of histamine on bronchial and gastrointestinal smooth muscles, and on capillaries. This drug also prevents histamine-induced pain and itching of the skin and mucous membranes.
A synthetic anabolic steroid related to dihydrotestosterone that has antiestrogenic effects. Dromostanolone inhibits the growth of estrogen receptor-presenting breast cancers; its virilizing effects limit its clinical usefulness. (NCI04)
The propionate salt form of dromostanolone, a synthetic anabolic steroid related to dihydrotestosterone that has antiestrogenic effects. Dromostanolone inhibits the growth of estrogen receptor-presenting breast cancers; its virilizing effects limit its clinical usefulness. (NCI)
A combined vaccine used to prevent infection with diphtheria and tetanus toxoid. This is used in place of DTP vaccine (DIPHTHERIA-TETANUS-PERTUSSIS VACCINE) when PERTUSSIS VACCINE is contraindicated.
An unclassified compound with local anesthetic effect. Dyclonine reversibly binds to activated sodium channels on the neuronal membrane, thereby decreasing the neuronal membrane's permeability to sodium ions, leading to an increased threshold for excitation. This reversibly stabilizes the membrane and inhibits depolarization, leading to the failure of a propagated action potential and subsequent conduction blockade. This results in a transient and reversible loss of sensation in a localized area of the body.
A organoselenium compound with anti-inflammatory, anti-oxidant and cytoprotective activity. Ebselen acts as a glutathione peroxidase mimetic and is thereby able to prevent cellular damage induced by reactive oxygen species (ROS). In addition, this agent inhibits the activity of a variety of enzymes including nitric oxide synthase (NOS), 5-lipoxygenase, cyclooxygenase, protein kinase C (PKC), NADPH oxidase and gastric H+/K+-ATPase. Furthermore, ebselen may be neuroprotective due to its ability to neutralize free radicals upon NMDA receptor activation thus, reducing lipoperoxidation mediated by glutamate-induced excitotoxicity.
A highly purified omega-3 fatty acid that can decrease serum triglyceride levels. Ethyl icosapentate reduces serum triglycerides without an increase in LDL cholesterol, but increases the cholesterol and triglyceride content in skeletal muscle.
A (2-chloroethy1)nitrosourea derivative related to carmustine, with antineoplastic activity.
A topical anesthetic cream, containing lidocaine 2.5% and prilocaine 2.5%, that provides neuralgia pain relief by causing loss of cutaneous sensation through reversible blockade of conduction in nerve fibers. (NCI)
A diphenylmethane derivative with hypocholesterolemic properties. Eniclobrate increases the activity of cholesterol-7 alpha hydroxylase and lowers serum and liver cholesterol levels, but raises liver triglyceride levels. It also reduces the percentage of esterified cholesterol present in the serum.
A pyrimidine antimetabolite converted to Cytarabine in the body. (NCI)
Staphylococcal enterotoxin C. A superantigen and member of a family of genetically related proteins produced by Staphylococcus aureus and Streptococcus pyogenes. An extremely potent activator of T lymphocytes when presented on MHC class II antigens.
A substituted benzimidazole derivative with activity against rhinoviruses and enteroviruses. Enviroxime is a kinase inhibitor that targets viral protein 3A and 3AB, which are involved in viral RNA replication complex formation, thereby resulting in suppression of viral replication.
One of several basic proteins released from EOSINOPHIL cytoplasmic granules. Eosinophil major basic protein is a 14-kDa cytotoxic peptide with a pI of 10.9. In addition to its direct cytotoxic effects, it stimulates the release of variety of INFLAMMATION MEDIATORS.
A 19-kDa cationic peptide found in EOSINOPHIL granules. Eosinophil-derived neurotoxin is a RIBONUCLEASE and may play a role as an endogenous antiviral agent.
A (-)-epicatechin with a galloyloxy (trihydroxybenzoyloxy) group instead of the hydroxyl group at C-3; (-)-epicatechin esterified with gallic acid (trihydroxybenzoid acid) at C-3.
A phenolic antioxidant found in a number of plants such as green and black tea. It inhibits cellular oxidation and prevents free radical damage to cells. It is under study as a potential cancer chemopreventive agent. (NCI)
An androgenic anabolic steroid having potent anti-estrogenic effect, which inhibits the progression of estrogen-stimulated cancers such as breast cancer. (NCI)
A non-steroidal ESTROGEN generated when soybean products are metabolized by certain bacteria in the intestines.
A water soluble congener of tubulozole and a tubulin binding agent with potential antimitotic and antineoplastic activities. Erbulozole targets and binds to tubulin, thereby preventing the polymerization of tubulin. This may lead to an inhibition of cell division and induction of apoptosis.
A homocysteine-derived thiol derivative with mucolytic and free radical scavenging properties. Erdosteine and its metabolites modulate mucus production and viscosity, by which facilitating mucociliary transport and improving expectoration. This agent also suppresses the chemical-induced cough reflex as well as protects lung tissues from damages caused by cigarette smoking mediated through free radicals scavenging.
Vaccines or candidate vaccines used to prevent or treat both enterotoxigenic and enteropathogenic Escherichia coli infections.
The cypionate salt form of estradiol, the most potent, naturally produced estrogen. Estradiol cypionate diffuses through the cell membrane and binds to and subsequently activates the nuclear estrogen receptor found in the reproductive tract, breast, pituitary, hypothalamus, liver, and bone. The activated complex binds to the estrogen response element on the DNA and activates the transcription of genes involved in the functioning of the female reproductive system and secondary sex characteristics.
The synthetic dipropionate ester of estradiol, a steroid sex hormone vital to the maintenance of fertility and secondary sexual characteristics in females. As the primary, most potent estrogen hormone produced by the ovaries, estradiol binds to and activates specific nuclear receptors. This agent exhibits mild anabolic and metabolic properties, and increases blood coagulability. (NCI04)
The parenterally-administered synthetic valerate ester of estradiol, a steroid sex hormone vital to the maintenance of fertility and secondary sexual characteristics in females. As the primary, most potent estrogen hormone produced by the ovaries, estradiol binds to and activates specific nuclear receptors. This agent exhibits mild anabolic and metabolic properties, and increases blood coagulability. (NCI04)
An aqueous substance that is the sulfate salt form of estrone. (NCI)
A 2-nitroimidazole with radiosensitizing properties. Etanidazole depletes glutathione and inhibits glutathione transferase, thereby enhancing the cytotoxicity of ionizing radiation. This agent may also be useful as an imaging agent for identifying hypoxic, drug-resistant regions of primary tumors or metastases. (NCI04)
A synthetic preparation of oleic acid and ethanolamine, a first generation monoethanolamine with sclerotherapeutic activity. Ethanolamine oleate causes an acute, dose-related inflammatory reaction of the intimal endothelium of the vein. This leads to scarring at the inner wall of the veins and possible occlusion of the veins. The oleic acid component may also transiently activate coagulation and fibrinolytic systems through the release of tissue factor and activation of Hageman factor.
A non-steroidal anti-inflammatory agent and cyclooxygenase-2 (COX-2) inhibitor with potent analgesic and anti-arthritic properties. It has been shown to be effective in the treatment of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; and in the alleviation of postoperative pain (PAIN, POSTOPERATIVE).
An orally-available combination of clofibrate and niacin linked together by an ester bond. In the body clofibrate and niacin separate, acting as a controlled-release formulation.
A phosphate salt of a semisynthetic derivative of podophyllotoxin. Etoposide binds to the enzyme topoisomerase II, inducing double-strand DNA breaks, inhibiting DNA repair, and resulting in decreased DNA synthesis and tumor cell proliferation. Cells in the S and G2 phases of the cell cycle are most sensitive to this agent. (NCI04)
A lipophilic, diaminopyrimidine folate antagonist with potential antineoplastic activity. Etoprine inhibits dihydrofolate reductase, resulting in decreased cellular folate metabolism. This may eventually result in a reduction of cellular growth and the induction of apoptosis. In addition, this agent inhibits histamine-N-methyltransferase, resulting in decreased histamine catabolism. Lipid-soluble etoprine is capable of crossing the blood-brain barrier.
A long-acting loop diuretic. Etozolin appears to be rapidly metabolized to its active metabolite ozolinone.
A lipophilic derivative of the adrenergic blocking agent propranolol with sympatholytic activity. Exaprolol competitively binds to and blocks beta-adrenergic receptors in the heart and vascular smooth muscle, thereby causing negative chronotropic and inotropic effects leading to a reduction in cardiac output.
A fluorinated nucleotide antimetabolite analog of the antiviral agent vidarabine (ara-A) with antineoplastic activity. Administered parenterally as a phosphate salt, fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite may inhibit DNA polymerase alpha, ribonucleotide reductase and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth. (NCI04)
An orally-active pyrimidine analogue of an aza-substituted cytidine in which the ribose moiety is replaced by an arabinose sugar. Similar in action to cytarabine, fazarabine is phosphorylated by deoxycytidine kinase to a triphosphate form which competes with thymidine for incorporation into DNA; its incorporation into DNA inhibits DNA synthesis, resulting in tumor cell death and tumor necrosis. The presence of deoxycytidine kinase in a tumor is a determinant of tumor sensitivity to this drug. (NCI04)
A PEGylated phenylcarbamate derivative that acts as an antagonist of NMDA RECEPTORS. It is used as an anticonvulsant, primarily for the treatment of SEIZURES in severe refractory EPILEPSY.
The active form of fenofibrate, a synthetic phenoxy-isobutyric acid derivate with antihyperlipidemic activity.
A benzazepine derivative with vasodilatory and antihypertensive properties. Fenoldopam, a dopamine (DA) receptor agonist, binds specifically to peripheral DA1 receptors and to alpha-2 adrenoceptors with moderate affinity. However, this agent exhibits no significant affinity to DA2, other alpha adrenergic, beta adrenergic, muscarinic, or serotonergic receptors. Receptor binding modulates the transmembrane flux of ions, thereby stimulating adenylate cyclase activity, as well as the release of prolactin. This results in vasodilatation, increased renal blood flow thereby enhancing natriuresis and diuresis leading to a lowering in diastolic blood pressure.
A quinazolinone sulphonamide-based diuretic, structurally related to metolazone, with thiazide-like activity. As a thiazide-like diuretic, fenquizone acts by blocking reabsorption of sodium in the proximal tubule and the ascending branch of the loop of Henle. This causes an increase in diuresis with the elimination of chloride and sodium.
An orally-active synthetic phenylretinamide analogue of retinol (vitamin A) with potential antineoplastic and chemopreventive activities. Fenretinide binds to and activates retinoic acid receptors (RARs), thereby inducing cell differentiation and apoptosis in some tumor cell types. This agent also inhibits tumor growth by modulating angiogenesis-associated growth factors and their receptors and exhibits retinoid receptor-independent apoptotic properties. (NCI04)
An antibacterial and antifungal agent for topical use, mostly used now in veterinary medicine.
A chelating agent with strong binding affinity for thallium, cesium, and other ions. Ferric hexacyanoferrate is used for the treatment of acute and chronic thallium and cesium poisoning. This agent is not absorbed in the gastrointestinal tract and it chelates thallium or cesium ion in the intestines. The resulting complex is eliminated via the feces.
A glucaric acid-iron conjugate that is used in the treatment of IRON-DEFICIENCY ANEMIA, including in patients with chronic kidney disease, when oral iron therapy is ineffective or impractical.
A superparamagnetic iron oxide nanoparticle coated with a low molecular weight semi-synthetic carbohydrate, polyglucose sorbitol carboxymethyl ether, with potential anti-anemic and imaging properties. After intravenous administration, ferumoxytol replaces iron stores with fewer side effects compared to the use of oral iron. In addition, this agent generates T1 relaxation, producing a magnetic field and enhancing T2 relaxation, thereby darkening contrast media-containing structures in magnetic resonance imaging (MRI). Due to small particle size, ferumoxytol remains in the intravasculature for a prolonged period and so may be used as a blood pool agent.
The fumarate salt form of the mineral iron. Administration of ferrous fumarate results in elevation of serum iron concentration, which is then assimilated into hemoglobin, required for the transport of oxygen, or trapped in the reticuloendothelial cells for storage. This agent is used as a dietary supplement, and to prevent or treat iron deficiency related syndromes.
A form of mineral iron for oral administration, Ferrous Gluconate is absorbed in the stomach and small intestine and combines with apoferritin to form ferritin, which is stored in the liver, spleen, red bone marrow, and intestinal mucosa. Important in transport of oxygen by hemoglobin to the tissues, iron is also found in myoglobin, transferrin, and ferritin, and is as a component of many enzymes such as catalase, peroxidase, and cytochromes. (NCI04)
A sulfate salt of mineral iron formulated for oral administration and used as a dietary supplement, ferrous sulfate is absorbed in the stomach and small intestine and combines with apoferritin to form ferritin, which is stored in the liver, spleen, red bone marrow, and intestinal mucosa. Important in transport of oxygen by hemoglobin to the tissues, iron is also found in myoglobin, transferrin, and ferritin, and is a component of many enzymes such as catalase, peroxidase, and cytochromes.
A synthetic 4-azasteroid compound. Finasteride competitively binds to and inhibits steroid type II 5-alpha-reductase in the prostate gland, liver, and skin, thereby interfering with the enzymatic conversion of testosterone to 5-dihydrotestosterone (DHT) and reducing serum DHT levels. The reduction in serum DHT levels results in diminished stimulation of androgen receptors in the nuclei of prostate cells and, so, diminished prostate cell proliferation.
A flavonoid typically with a double bond between C-2 and C-3, a carbonyl (C=O) function at C-4, and no hydroxyl group at C-3.
A synthetic flavonoid with vascular targeting properties. Flavone acetic acid exhibits an antiproliferative effect on endothelial cells as a result of a superoxide-dependent mechanism, which induces changes in permeability of the vasculature of the tumor. This agent may stimulate tumor necrosis and promote shunting of blood flow to viable regions of the tumor, increasing their oxygenation and rendering them more susceptible to the antitumor effects of hyperthermia and ionizing radiation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40152&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40152&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1101"" NCI Thesaurus)
An analog of D-alanine that is active against gram-negative bacteria. Fludalanine is an irreversible inhibitor of bacterial alanine racemase, an enzyme required for the generation of the bacterial cell wall precursor, D-alanine.
The phosphate salt of a fluorinated nucleotide antimetabolite analog of the antiviral agent vidarabine (ara-A) with antineoplastic activity. Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite may inhibit DNA polymerase alpha, ribonucleotide reductase and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth.
A synthetic corticosteroid with antiinflammatory and antiallergic properties. Flunisolide is a glucocorticoid receptor agonist that binds to cytoplasmic glucocorticoid receptors and subsequently translocates to the nucleus where it initiates the transcription of glucocorticoid-responsive genes such as lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both are potent mediators of inflammation.
A synthetic glucocorticoid with anti-inflammatory and antipruritic activities. Fluocinolone binds the glucocorticoid receptor, followed by translocation of the ligand-receptor complex to the nucleus and transcription activation of genes containing glucocorticoid-responsive elements. Lipocortin-1 is one factor induced by fluocinolone that interacts with and inhibits cytosolic phospholipase 2 alpha, thereby preventing phospholipase translocation to the perinuclear membrane and subsequent release and conversion of arachidonic acid to inflammatory prostaglandins. In addition, MAPK phosphatase 1 is induced, thereby preventing the triggering of the MAPK cascade resulting in pro-inflammatory effects via Jun N-terminal kinase and c-Jun. Finally, fluocinolone binds to and inhibits nuclear factor kappa-B directly, resulting in inhibition of cyclooxygenase 2 transcription and subsequent prostaglandin synthesis.
A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor.
An alkylating agent with potential antineoplastic activity. Fluorodopan alkylates DNA at the N7 position of guanine. Alkylating agents exert cytotoxic and, in some cases, chemotherapeutic effects by transferring alkyl groups to DNA, thereby damaging DNA and interfering with DNA replication and cell division. (NCI04)
emulsion of perfluorochemicals (hydrocarbons with all hydrogen atoms replaced by fluorine) that can carry dissolved molecular oxygen and so be used as a blood substitute; it also accumulates in tumors and has radiosensitizer properties.
The decanoate salt form of fluphenazine, a phenothiazine with antipsychotic activity. Fluphenazine decanoate exerts its actions by blocking postsynaptic dopamine D2 receptors in the limbic, cortical system and basal ganglia. This prevents the actions of dopamine, thereby reducing the hallucinations and delusions that are associated with schizophrenia.
A thiotepa derivative with potential antineoplastic alkylating activity. Although the exact mechanism of action of pumitepa has yet to be fully elucidated, this agent appears to work through alkylation, thereby causing DNA damage and cell cycle arrest.
A long-acting beta-adrenergic receptor agonist with bronchodilator activity. Formoterol selectively binds to beta-2 adrenergic receptors in bronchial smooth muscle, thereby activating intracellular adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, relieve bronchospasms, improve mucociliary clearance and reduce mediator substance release from inflammatory cells, especially from mast cells.
The diphosphate ester of a synthetic, nonsteroidal form of estrogen. A well-known teratogen and carcinogen, diethylstilbestrol inhibits the hypothalamic-pituitary-gonadal axis, thereby blocking the testicular synthesis of testosterone, lowering plasma testosterone, and inducing a chemical castration.
A chloroethylating nitrosourea with antineoplastic activity. Fotemustine alkylates guanine by forming chloroethyl adducts at the 6 position of guanine, resulting in N1-guanine and N3-cytosine cross linkages, inhibition of DNA synthesis, cell cycle arrest, and finally apoptosis. This agent is lipophilic and crosses the blood-brain barrier.
A pentaethyleneimine derivative with antineoplastic alkylating activity. Fotretamine causes chromosomal breaks in lymphocytes which contributes to its immunosuppressive activity.
A pharmacologic form of follicle-stimulating hormone used in the treatment of infertility.
A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.
A hydrated nitrate salt of the group IIIa element gallium with potential use in the treatment of malignancy-associated hypercalcemia. Gallium nitrate localizes preferentially to areas of bone resorption and remodeling and inhibits osteoclast-mediated resorption by enhancing hydroxyapatite crystallization and reduction of bone mineral solubility. This agent also increases calcium and phosphorous deposition into bone and may increase collagen synthesis. (NCI04)
A polyunsaturated long-chain fatty acid with an 18-carbon backbone and exactly three double bonds, originating from the 6th, 9th and 12th positions from the methyl end, with all double bonds in the cis- configuration.
A class I ribosome-inactivating protein (RIP) and toxin derived from the seeds of the plant Gelonium multiflorum. Gelonin (rGel) exerts N-glycosidase activity on the 28S ribosomal RNA (rRNA) unit of eukaryotic ribosomes by cleaving out adenine at the 4324 site, which depurinates rRNA, inactivates ribosomes, inhibits protein synthesis, and results in cell death. Used as the toxin moiety of certain immunotoxins and linked to antibodies specific for a tumor-associated antigen (TAA), gelonin can be targeted to and induce specific cytotoxicity in tumor cells expressing the TAA.
A soy-derived isoflavone and phytoestrogen with antineoplastic activity. Genistein binds to and inhibits protein-tyrosine kinase, thereby disrupting signal transduction and inducing cell differentiation. This agent also inhibits topoisomerase-II, leading to DNA fragmentation and apoptosis, and induces G2/M cell cycle arrest. Genistein exhibits antioxidant, antiangiogenic, and immunosuppressive activities. (NCI04)
A terpene with two isoprene units head to tail with hydroxyl group attached to the head methyl group. The chemical structure is CC(=CCC\C(=C\CO)\C)C.
A polycyclic lactone quassinoid phytochemical isolated from the seeds of Hannoa undulata and other plant species with potential antineoplastic activity. This agent also has antiviral and antitumor properties. (NCI04)
A fluoro-containing sulfadiazine derivative with hypoglycemic activity. Although not technically a sulfonylurea compound, gliflumide targets the sulfonylurea receptor and exerts a similar action as glibenclamide.
A long-acting, third-generation sulfonylurea with hypoglycemic activity. Compared to other generations of sulfonylurea compounds, glimepiride is very potent and has a longer duration of action. This agent is metabolized by CYP2C9 and shows peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic activity.
A potent, second-generation sulfonylurea with antihyperglycemic activity. Like other second-generation compounds, gliquidone exerts greater binding affinity to SUR1 and increased potency compared to first-generation compounds. In addition, this agent exerts peroxisome proliferator-activated receptor (PPAR) gamma agonistic activity.
A second-generation sulfonylurea with antihyperglycemic activity. Glisolamide is comparable to glyburide and gliquidone in controlling blood glucose levels.
A second-generation sulfonylurea with antihyperglycemic activity. Like other second-generation compounds, glisoxepide exerts greater binding affinity than the first-generation compounds. Glisoxepide shows peroxisome proliferator-activated receptor (PPAR) gamma agonistic activity, has a short half-life and is excreted in both the bile and urine.
A naturally occurring polyhydroxy acid (PHA) with metal chelating, moisturizing and antioxidant activity. Gluconolactone can be produced by enzymatic oxidation of D-glucose oxidation. Its ability in free radicals scavenging accounts for its antioxidant property. It is used in cosmetic product and as a coagulant in tofu processing. (NCI05)
An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. (Stedman, 26th ed)
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
A GLUTATHIONE dimer formed by a disulfide bond between the cysteine sulfhydryl side chains during the course of being oxidized.
A sulfonamide derivative with antihyperglycemic activity. Like sulfonylureas, glybuzole is able to lower blood glucose levels by increasing the release of insulin from pancreatic beta cells.
A saponin-like compound that provides the main sweet flavor for Glycyrrhiza glabra (licorice), with potential immunomodulating, anti-inflammatory, hepato- and neuro-protective, and antineoplastic activities. Glycyrrhizin modulates certain enzymes involved in inflammation and oxidative stress, and downregulates certain pro-inflammatory mediators, thereby protecting against inflammation- and reactive oxygen species (ROS)-induced damage. Glycerrhizin may also suppress the growth of susceptible tumor cells.
A cyclopentyl containing, second-generation sulfonylurea and structurally similar to glibenclamide with hypoglycemic activity. Glisentide, also known as glypentide, appears to improve total lipid and cholesterol levels.
The naturally occurring acetic acid form of gossypol, and an orally available polyphenolic aldehyde derived mostly from cottonseed with potential antineoplastic activity. The biologic activities of gossypol acetic acid are similar to those of gossypol and include suppression of DNA replication, inhibition of tumor cell proliferation, and male contraceptive effects. (NCI04)
A carbazole derivative with antiemetic activity. As a selective serotonin receptor antagonist, ondansetron competitively blocks the action of serotonin at 5HT3 receptors, resulting in suppression of chemotherapy- and radiotherapy-induced nausea and vomiting. (NCI04)
A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients.
Haemophilus influenzae type b vaccine, PRP-D conjugate.
A synthetic benzodiazepine derivative with anxiolytic property. Halazepam potentiates the inhibitory activities of gamma-aminobutyric acid (GABA) by binding to the benzodiazepine-GABA-A-chloride ionophore receptor complex located in the limbic, thalamic, and hypothalamic regions of the central nervous system (CNS). This increases the frequency of chloride channel opening, allowing the flow of chloride ions into the neuron and ultimately leading to membrane hyperpolarization and a decrease in neuronal excitability.
An orally-active quinazolinone alkaloid with potential antineoplastic activity. Halofuginone interferes with the signaling pathway of transforming growth factor beta (TGF beta) and inhibits expression of matrix metalloproteinase 2, thereby inhibiting collagen type I synthesis and inducing extracellular matrix degradation, resulting in inhibition of angiogenesis, tumor growth, or metastasis.
The decanoate ester of haloperidol, a phenylbutylpiperadine derivative with antipsychotic, neuroleptic and antiemetic effects. Haloperidol competitively blocks postsynaptic dopamine (D2) receptors in the mesolimbic system of the brain leading to anti-delusionary and anti-hallucinogenic effects. The antagonistic activity mediated through D2 dopamine receptors in the chemoreceptive trigger zone (CTZ) account for its antiemetic activity.
An antifungal agent used as a topical cream. It was discontinued in favor of newer antifungals with fewer side effects.
A non-infectious mixture containing recombinant hepatitis B surface antigen (HBsAg) in a liquid vehicle. Immunization with the hepatitis B vaccine induces the formation of specific anti-hepatitis B antibodies and an active immunity against hepatitis B infection.
A bisulfamic ester which is similar in structure to busulfan and belongs to the family of drugs known as alkylsulfonate alkylating agents. Hepsulfam forms covalent linkages with nucleophilic centers in DNA, resulting in depurination, base miscoding, strand scission, DNA-DNA and DNA-protein cross-linking, and cytotoxicity. (NCI04)
A flavanone with hydroxyl groups at C-5, C-7, and C-5' and a methoxyl group at C-4'.
A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.
A hybrid polar-planar compound with potential antineoplastic activity that induces terminal differentiation, inhibits cell growth, and causes apoptosis in several tumor cell lines. Its precise mechanism of action is unknown. (NCI04)
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*11 allele family.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*24 allele family.
A synthetic tertiary amine alkaloid with antimuscarinic properties. Homatropine, a competitive inhibitor of acetylcholine at the muscarinic receptor, blocks parasympathetic nerve stimulation.
The methylbromide salt of homatropine, a synthetic tertiary amine alkaloid with antimuscarinic properties. Homatropine methylbromide, a competitive inhibitor of acetylcholine at the muscarinic receptor, blocks parasympathetic nerve stimulation, thereby inhibiting pepsin and gastrin secretion. When administered in high doses, this drug produces inhibitory effects on acetylcholine activity, specifically on smooth muscle located in the gastrointestinal, biliary, and genitourinary tracts, resulting in an anti-spasmodic effect.
A semisynthetic formulation of the cytotoxic plant alkaloid homoharringtonine isolated from the evergreen tree Cephalotaxus with potential antineoplastic activity. Omacetaxine mepesuccinate binds to the 80S ribosome in eukaryotic cells and inhibits protein synthesis by interfering with chain elongation. This agent also induces differentiation and apoptosis in some cancer cell types.
A derivative of isoxazole used for its immunosuppressive and anti-inflammatory properties. As a prodrug, leflunomide is converted to an active metabolite, A77 1726, which blocks dihydroorotate dehydrogenase, a key enzyme of de novo pyrimidine synthesis, thereby preventing the expansion of activated T lymphocytes. This agent also inhibits various protein tyrosine kinases, such as protein kinase C (PKC), thereby inhibiting cell proliferation. (NCI04)
The synthetic sulfate salt of hydrazine, a derivative of ammonia. Hydrazine inhibits the enzyme phosphoenol pyruvate carboxykinase, thereby blocking gluconeogenesis. This agent has been reported to decrease the excessive energy needs and cachexia of cancer patients. Classified as a likely human carcinogen, hydrazine sulfate is also a weak inhibitor of mono-amine oxidase (MAO). (NCI04)
The probutate salt form of hydrocortisone, a synthetic glucocorticoid receptor agonist with antiinflammatory, antipruritic and vasoconstrictive effects. Binding and activation of the glucocorticoid receptor results in the activation of lipocortin that in turn inhibits cytosolic phospholipase A2. Lack of phospholipase A2 prevents the release of arachidonic acid, precursor for inflammatory mediator prostaglandins and leukotrienes, from the cell membrane. Secondly, mitogen-activated protein kinase (MAPK) phosphatase 1 is induced, thereby leads to dephosphorylation and inactivation of Jun N-terminal kinase directly inhibiting c-Jun mediated transcription. Finally, transcriptional activity of nuclear factor (NF)-kappa-B is blocked, thereby inhibits the transcription of cyclooxygenase 2, which is essential for prostaglandin production.
The synthetic acetate salt form of hydrocortisone, a corticosteroid with anti-inflammatory and immunosuppressive properties. Hydrocortisone acetate initially binds to the cytoplasmic glucocorticoid receptor; then the receptor-ligand complex is translocated to the nucleus where it initiates the transcription of genes encoding for anti-inflammatory mediators, such as cytokines and lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes.
The valerate salt form of hydrocortisone, a synthetic glucocorticoid receptor agonist with antiinflammatory, antipruritic and vasoconstrictive effects. Binding and activation of the glucocorticoid receptor results in the activation of lipocortin that in turn inhibits cytosolic phospholipase A2. Lack of phospholipase A2 prevents the release of arachidonic acid, precursor for inflammatory mediator prostaglandins and leukotrienes, from the cell membrane. Secondly, mitogen-activated protein kinase (MAPK) phosphatase 1 is induced, thereby leads to dephosphorylation and inactivation of Jun N-terminal kinase directly inhibiting c-Jun mediated transcription. Finally, transcriptional activity of nuclear factor (NF)-kappa-B is blocked, thereby inhibits the transcription of cyclooxygenase 2, which is essential for prostaglandin production.
A network of cross-linked hydrophilic macromolecules used in biomedical applications fabricated by photopolymerization of polyethylene glycol dimethacrylate. Its general formulae is C3H5C(O)(OCH2CH2)nOC(O)C3H5 where n denotes a number of average polyglycol (OCH2CH2) repeats.
A metabolite of nicotine that is detectable in the urine of smokers.
A cationic dye with antifungal, antitrypanosomal, antimalarial, and carcinostatic activities. Hydroxystilbamidine is able to bind to DNA and RNA in a non-intercalating manner, and is a powerful inhibitor of ribonucleases, thereby impeding cellular processes in protozoa. This agent was also shown to bind to and stablize trypanosomal lysosomes. Hydroxystilbamidine is commonly used as a diagnostic agent in neuroanatomy and as a histochemical stain.
An anthraquinone derivative that is naturally found in the yellow flower of Hypericum perforatum (St. John's wort) with antidepressant, potential antiviral, antineoplastic and immunostimulating activities. Hypericin appears to inhibit the neuronal uptake of serotonin, norepinephrine, dopamine, gamma-amino butyric acid (GABA) and L-glutamate, which may contribute to its antidepressant effect. Hypericin may also prevent the replication of encapsulated viruses probably due to inhibition of the assembly and shedding of virus particles in infected cells. This agent also exerts potent phototoxic effects by triggering apoptotic signaling that results in formation of reactive oxygen species.
A semisynthetic, inert, viscoelastic polymer. It is used as an ophthalmic lubricant and as an excipient in oral medications.
A fluorinated ether that is used as a volatile anesthetic for maintenance of general anesthesia.
An indole derivative and 5-HT3 RECEPTOR antagonist that is used for the prevention of nausea and vomiting.
A benzodioxane-linked imidazole that has alpha-2 adrenoceptor antagonist activity.
A synthetic derivative of imidazole with potent antineoplastic properties. Imidazole mustard alkylates DNA, preferentially at guanine residues, resulting in DNA interstrand crosslinks and inhibition of DNA replication and RNA and protein synthesis. (NCI04)
A highly potent and specific histamine H2 receptor agonist. It has been used diagnostically as a gastric secretion indicator.
A low molecular weight fraction of human leukocyte dialysates with potential immunostimulatory activity. IMREG-1 is shown to augment and accelerate human delayed type hypersensitivity (DTH) to recall antigen in vivo, potentiate production of interleukin-2 (IL-2) and interferon gamma, and induce expression of IL-2 receptor in peripheral blood mononuclear cells. These effects are attributed to the peptides Tyr-Gly and Tyr-Gly-Gly, which are identical to the N-terminal end of the enkephalins. Studies in HIV patients have shown that this agent may delay progression to more serious disease and improve laboratory markers.
A membrane vesicle/ribosome preparation derived from the bacterium Serratia marcescens with immunomodulatory activity. ImuVert triggers interferon (IFN) gamma production through binding the low affinity IgG Fc receptor type III (CD16) on natural killer (NK) cells. This agent works synergistically with interleukin-2 further enhancing IFN gamma production. In addition, ImuVert is capable of inducing peripheral blood mononuclear cells (PBMC), from the cord blood of newborn infants lacking NK activity, to exhibit NK activity.
An orally active, indanone-based loop diuretic that consists of a racemic mixture. The (-) enantiomer is natriuretic, and the (+) enantiomer is uricosuric.
A natural pyrrolizidine alkaloid with antineoplastic properties. Indicine-N-oxide alkylates and crosslinks DNA. (NCI04)
A naturally occurring, orally available cleavage product of the glucosinolate glucobrassicanin, a natural compound present in a wide variety of plant food substances including members of the family Cruciferae with antioxidant and potential chemopreventive properties. Indole-3-carbinol scavenges free radicals and induces various hepatic cytochrome P450 monooxygenases. Specifically, this agent induces the hepatic monooxygenase cytochrome P4501A1 (CYP1A1), resulting in increased 2-hydroxylation of estrogens and increased production of the chemoprotective estrogen 2-hydroxyestrone.
A toxic purine analogue. Inosine dialdehyde inhibits ribonucleotide reductase, resulting in decreased synthesis of DNA, RNA, and proteins, and G2/M-phase cell cycle arrest. This agent also forms stable covalent crosslinks in proteins, thereby inhibiting the activity of enzymes involved in nucleic acid synthesis. (NCI04)
A niacin formulation that contains no free niacin, but can be hydrolyzed to release free niacin in vivo. Use of inositol niacinate is associated with less flushing than that seen with the use of free niacin.
A benzoquinone-based antineoplastic agent. Inproquone was never marketed.
Complex of iron atoms chelated with carbonyl ions.
A synthetic mustard compound with potential antineoplastic activity. An active metabolite of ifosfamide covalently linked to the amino acid lysine for stability, palifosfamide irreversibly alkylates and cross-links DNA through GC base pairs, resulting in irreparable 7-atom inter-strand cross-links; inhibition of DNA replication and cell death follow. Unlike ifosfamide, this agent is not metabolized to acrolein or chloroacetaldehyde, metabolites associated with bladder and CNS toxicities. In addition, because palifosfamide does not require activation by aldehyde dehydrogenase, it may overcome the tumor resistance seen with ifosfamide.
The mononitrate salt form of isosorbide, an organic nitrate with vasodilator activity. Isosorbide mononitrate relaxes vascular smooth muscle by formation of the free radical nitric oxide (NO), which is identical to the endothelium-derived relaxing factor (EDRF). NO activates guanylyl cyclase, thereby increasing the synthesis of cGMP within smooth muscle, resulting in dephosphorylation of light chain myosin and relaxation of peripheral arteries and veins. In addition, isosorbide mononitrate relaxes coronary arteries, thereby increasing the blood circulation through the ischemic area. (NCI05)
A hypolipidemic and hypouricemic compound with moderate anti-inflammatory activity.
A synthetic triazole agent with antimycotic properties. Formulated for both topical and systemic use, itraconazole preferentially inhibits fungal cytochrome P450 enzymes, resulting in a decrease in fungal ergosterol synthesis. Because of its low toxicity profile, this agent can be used for long-term maintenance treatment of chronic fungal infections. (NCI04)
The oil extracted from the seeds of Simmondsia chinensis. Jojoba oil is used primarily in cosmetics.
A second generation, selective histamine H1 receptor antagonist with anti-allergic activity. Emedastine reversibly and competitively blocks histamine by binding to H1 receptors, thus blocking its downstream activity. As a result this agent interferes with mediator release from mast cells either by inhibiting calcium ion influx across mast cell/basophil plasma membrane or by inhibiting intracellular calcium ion release within the cells. In addition, emedastine may also inhibit the late-phase allergic reaction mediated through leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect. Upon ocular administration, emedastine causes a dose-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva. Emedastine does not affect adrenergic, dopamine, or serotonin receptors.
A fibroblast growth factor that is a specific mitogen for EPITHELIAL CELLS. It binds a complex of HEPARAN SULFATE and FIBROBLAST GROWTH FACTOR RECEPTOR 2B.
An agent that reacts with guanine to create a covalent adduct. In vivo, Kethoxal reacts with 30S ribosomal subunits yielding inactive ribosomes.
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity.
A semisynthetic water-soluble disulfide derivative of the antineoplastic antibiotic mitomycin C. Activated by serum and glutathione, KW-2149 causes interstrand DNA cross-links and DNA-protein cross-links, resulting in single-strand DNA breaks and inhibition of DNA synthesis. (NCI04)
A derivative of benzodiazepine that acts on the cholecystokinin A (CCKA) receptor to antagonize CCK-8's (SINCALIDE) physiological and behavioral effects, such as pancreatic stimulation and inhibition of feeding.
An orally-active agent with potential antineoplastic activity. Carboxyamidotriazole binds to and inhibits non-voltage-operated Ca2+ channels, blocking both Ca2+ influx into cells and Ca2+ release from intracellular stores and resulting in the disruption of calcium channel-mediated signal transduction and inhibition of vascular endothelial growth factor (VEGF) signaling, endothelial proliferation, and angiogenesis. This agent may also inhibit tumor cell growth, invasion and metastasis. (NCI04)
A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed)
A phenyltriazine compound, sodium and calcium channel blocker that is used for the treatment of SEIZURES and BIPOLAR DISORDER.
A percutaneous enhancer. Upon application to the skin, laurocapram interacts with lipids in the stratum corneum and may enhance the ability of the skin to absorb a hydrophilic chemical.
A compound isolated from strains of Streptomyces griseolavendus that may exert antitumor activity by inhibition of protein tyrosine kinase and tubulin polymerization. (NCI)
Secreted by activated natural killer lymphocytes as a 50-kDa glycoprotein lymphokine, Leukoregulin can up regulate the expression of hyaluronan and prostaglandin-endoperoxide H synthase 2 (PTGS2), the inflammatory cyclooxygenase. Leukoregulin shows tumor growth inhibitory activity, enhances membrane permeability, and promotes the uptake of cytotoxic drugs by tumors cells without affecting these processes in normal cells. (NCI)
A synthetic piperidine derivative with antihistamine properties. Levocabastine is a second generation histamine-1 receptor antagonist. When applied locally into the eye as a topical solution, this agent reduces itching, rhinorrhea and symptoms of allergic rhinitis or conjunctivitis.
A potent synthetic agonist of GONADOTROPIN-RELEASING HORMONE with 3-(2-naphthyl)-D-alanine substitution at residue 6. Nafarelin has been used in the treatments of central PRECOCIOUS PUBERTY and ENDOMETRIOSIS.
A naturally occurring class of MONOTERPENES which occur as a clear colourless liquid at room temperature. Limonene is the major component in the oil of oranges which has many uses, including as flavor and fragrance. It is recognized as safe in food by the Food and Drug Administration (FDA).
A guanidine-based insulin secratogogue and structural analogue of pirogliride with hypoglycemic activity. Linogliride blocks ATP-sensitive potassium channels on the membranes of pancreatic beta cells which stimulates the secretion of insulin and improves glucose tolerance. This agent is associated with CNS toxicity.
A narrow-spectrum macrolide antibacterial agent that is used in the treatment of diarrhea associated with CLOSTRIDIUM DIFFICILE INFECTION.
A salt of lithium that has been used experimentally as an immunomodulator.
The tromethamide salt form of lodoxamide, a synthetic mast cell stabilizing compound with anti-inflammatory activity. Upon administration to the eye, lodoxamide tromethamide inhibits type I immediate hypersensitivity reaction by preventing the antigen-stimulated calcium influx into mast cells, thereby inhibiting release of histamine. Lodoxamide tromethamide also prevents the release of slow-reacting substances of anaphylaxis (SRS-A) and inhibits eosinophil chemotaxis.
A synthetic broad-spectrum fluoroquinolone with antibacterial activity. Lomefloxacin inhibits DNA gyrase, a type II topoisomerase involved in the induction or relaxation of supercoiling during DNA replication. This inhibition leads to a decrease in DNA synthesis during bacterial replication, resulting in cell growth inhibition and eventually cell lysis.
An indazole carboxylic acid derivative that exhibits radiosensitizing and antiparasitic effects and interferes with the multidrug resistance mechanism.
A piperidine histamine H1-receptor antagonist with anti-allergic properties and without sedative effects. Loratadine blocks the H1 histamine receptor and prevents the symptoms that are caused by histamine activity on capillaries, bronchial smooth muscle, and gastrointestinal smooth muscle, including vasodilatation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastrointestinal smooth muscle. Loratadine does not cross the blood-brain barrier and does not cause central nervous system effects.
A solution composed of iodine and potassium iodide, which can be used as a reagent and antiseptic, with potential use in cancer diagnosis. The iodine in Lugol's solution selectively binds to alpha-1,4 glucans found in polysaccharides, such as glycogen. Lugol's solution reacts with glycogen in normal, healthy non-keratinized, squamous epithelium and the iodine-glucan complex stains the glycogen-containing cells dark brown. Cancer cells are devoid of glycogen, so these cells will stay unstained. The presence of cancer cells can be detected by the degree of staining and the neoplastic cells can be surgically removed. High-grade intraepitheial neoplasia has almost no glycogen-containing epithelium.
The beta subunit of luteinizing hormone. It is a 15-kDa glycopolypeptide with structure similar to the beta subunit of the placental chorionic gonadatropin (CHORIONIC GONADOTROPIN, BETA SUBUNIT, HUMAN) except for the additional 31 amino acids at the C-terminal of CG-beta. Full biological activity of LH requires the non-covalently bound heterodimers of an alpha and a beta subunit. Mutation of the LHB gene causes HYPOGONADISM and infertility.
5,7,3',4'-tetrahydroxy-flavone, one of the FLAVONES.
A carotenoid and red pigment produced by tomatoes, other red fruits and vegetables, and photosynthetic algae. It is a key intermediate in the biosynthesis of other carotenoids, and has antioxidant, anti-carcinogenic, radioprotective, and anti-inflammatory properties.
An orally bioavailable, long-acting angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Lisinopril, a synthetic peptide derivative, specifically and competitively inhibits ACE, which results in a decrease in the production of the potent vasoconstrictor angiotensin II and, so, diminished vasopressor activity. In addition, angiotensin II-stimulated aldosterone secretion by the adrenal cortex is decreased which results in a decrease in sodium and water retention and an increase in serum potassium.
A synthetic oxazaphosphorine derivative with antineoplastic properties. Mafosfamide alkylates DNA, forming DNA cross-links and inhibiting DNA synthesis. Although closely related to cyclophosphamide, mafosfamide, unlike cyclophosphamide, does not require hepatic activation to generate its active metabolite 4-hydroxy-cyclophosphamide; accordingly, mafosfamide is potentially useful in the intrathecal treatment of neoplastic meningitis. (NCI04)
An organic salt or ester of maleic acid that could be conjugated to free base compounds/drugs to improve the physiochemical properties including stability, solubility and dissolution rate. (NCI)
An oligosaccharide derived from starch that is used as a food additive and as a carbohydrate supplement. As a supplement, maltodextrin is used to provide and sustain energy levels during endurance-oriented workouts o sports, and to help build muscle mass and support weight gain.
An aromatic alpha hydroxy acid used in the treatment of urinary tract infections and as an oral antibiotic.
A recombinant protein similar or identical to human mannan-binding lectin (MBL) with opsonin activity. MBL, a soluble pattern recognition receptor (PRR) collectin in the C-type lectin superfamily, is a plasma protein that plays an important role in innate immunity; MBL contains a carbohydrate recognition domain at one end and a collagen-like stalk domain at the other. Upon MBL binding to mannose residues on mannose-containing polysaccharides (mannans) on the surfaces of microorganisms, activation of the complement system results in the deposition of complement components (opsonization) and the clearance of the opsonized microorganisms by phagocytic cells. MBL is part of the mannan-binding lectin pathway (also known as the Ali/Krueger pathway), which has similarities to the classical complement pathway in that activation of C4 and C2 produce activated complement proteins further down the complement cascade. However, unlike the classical complement pathway, activation of this pathway is not antibody dependent.
An alkyl sulfonate with potential antineoplastic activity. Mannosulfan alkylates DNA, thereby producing DNA intra- or interstrand crosslinks, and ultimately results in inhibiting DNA replication and cell growth.
A synthetic vitamin D derivative usually formulated for topical dermatological use, antipsoriatic Calcipotriene (calcipotriol) competes equally with active 1,25-hydroxy-2D3 (the natural form of vitamin D) for 1,25-hydroxy-2D3 receptors in regulating cell proliferation and differentiation. It induces differentiation and suppresses proliferation of keratinocytes, reversing abnormal keratinocyte changes in psoriasis, and leads to normalization of epidermal growth. (NCI04)
An indole derivative with antiemetic activity. As a selective serotonin receptor antagonist, dolasetron mesylate competitively blocks the action of serotonin at 5HT3 receptors, resulting in suppression of chemotherapy- and radiotherapy-induced nausea and vomiting. (NCI04)
A combined vaccine used to prevent MEASLES; MUMPS; and RUBELLA.
measles, mumps, rubella, and varicella virus vaccine.
A broad-spectrum benzimidazole antifungal with potential antimitotic and antineoplastic activities. Although the exact mechanism of action is unclear, carbendazim appears to binds to an unspecified site on tubulin and suppresses microtubule assembly dynamic. This results in cell cycle arrest at the G2/M phase and an induction of apoptosis.
A synthetic progestin that is derived from 17-hydroxyprogesterone. It is a long-acting contraceptive that is effective both orally or by intramuscular injection and has also been used to treat breast and endometrial neoplasms.
A topical, synthetic glucocorticoid with metabolic, anti-inflammatory and anti-allergic properties. Medrysone exerts its effect by interacting with specific intracellular glucocorticoid receptors and subsequently binds to DNA to modify gene expression. This results in an induction of the synthesis of certain anti-inflammatory proteins while inhibiting the synthesis of certain inflammatory mediators. Consequently, an overall reduction in chronic inflammation and autoimmune reactions is accomplished.
Megestrol acetate is a progestogen with actions and uses similar to those of the progestogens in general. It also has anti-androgenic properties. It is given by mouth in the palliative treatment or as an adjunct to other therapy in endometrial carcinoma and in breast cancer. Megestrol acetate has been approved to treat anorexia and cachexia. (From Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
A benzamide belonging to the meglitinide class of antidiabetic agents with hypoglycemic activity. Meglitinide represents the basic structure of the meglitinide-type agents and is not used therapeutically.
A recombinant peptide chemically identical or similar to the endogenous alpha chemokine GRO1 (MGSA) protein. GRO1 protein belongs to a superfamily of proteins that includes interleukin-8 and platelet factor-4, beta-thromboglobulin (b-TG), IP-10, and ENA-78. It is chemotactic for neutrophils and plays a role in endothelial angiogenesis.
A menaquinone compound and form of vitamin K2 with potential antineoplastic activity. Menatetrenone may act by modulating the signalling of certain tyrosine kinases, thereby affecting several transcription factors including c-myc and c-fos. This agent inhibits tumor cell growth by inducing apoptosis and cell cycle arrest.
The oil extracted from various Brevoortia and Ethmidium species. Menhaden oil is used industrially in paint production and the tanning of leather as was as in livestock feeds.
An anabolic ether-modified form of the steroid epitiostanol. It has anti-estrogenic effect, which inhibits the progression of estrogen-stimulated cancers by competitive inhibition of estrogen binding to estrogen receptors. (NCI)
A cell wall fraction of bacillus Calmette-Guerin (BCG) obtained by menthol extraction with immunomodulating properties and potential use in cancer immunotherapy. (NCI04)
A spironolactone derivative and aldosterone antagonist with diuretic activity. Mespirenone, after in vivo metabolization, inhibits aldosterone synthase (steroid 18-hydroxylase), thereby preventing the synthesis of aldosterone in addition to the synthesis of other mineralocorticoids. The blockade of aldosterone synthesis results in increased sodium and water excretion while reducing potassium excretion within the kidney. Mespirenone has a short half-life and is metabolized completely into active metabolites.
A derivative of isoniazid, a synthetic derivative of nicotinic acid, with antituberculosis properties.
The hippurate salt form of methenamine, a prodrug and inactive weak base that slowly hydrolyzes in acidic urine to ammonia and the effective, urinary tract antiseptic formaldehyde. Formaldehyde probably exerts its antibacterial effect by denaturation of protein. Depending on the urinary concentrations, formaldehyde is either bactericidal or bacteriostatic. Formaldehyde urinary concentrations are dependent on urine pH, volume, and flow rate. Formaldehyde acts as an antibacterial agent against gram-positive and gram-negative organisms.
A diaminopyrimidine folate antagonist with potential antineoplastic activity. Metoprine inhibits dihydrofolate reductase, resulting in decreased cellular folate metabolism and cell growth; it also inhibits histamine-N-methyltransferase, resulting in decreased histamine catabolism. Lipid-soluble metoprine is capable of crossing the blood-brain barrier. (NCI04)
An orally bioavailable small molecule inhibitor with potential adjuvant activity. Methoxyamine covalently binds to apurinic/apyrimidinic (AP) DNA damage sites and inhibits base excision repair (BER), which may result in an increase in DNA strand breaks and apoptosis. This agent may potentiate the anti-tumor activity of alkylating agents.
A member of the homologous series of dimethane sulphonic acid esters with alkylating properties. Methylene dimethane sulfonate alkylates DNA, resulting in interstrand DNA crosslinking, inhibition of DNA replication, disruption of the cell cycle, and cell death.
A water-soluble organic solvent. As an adjuvant antineoplastic agent, N-methylformamide depletes cellular glutathione, a key molecule involved in the antioxidation of reactive oxygen species (ROS) and other free radicals, thereby enhancing ionizing radiation-induced DNA cross-linking in and terminal differentiation of tumor cells. (NCI04)
A methyl derivative of noroxymorphone with selective, opioid-receptor antagonistic activity. Methylnaltrexone displaces opioids from peripheral opioid receptors in the gastrointestinal tract, the bladder, and the skin, resulting in decreases in opioid-related constipation, urinary retention, and pruritis, respectively. Methylnaltrexone does not cross the blood-brain barrier and does not affect the centrally-mediated analgesic effect of opioids.
An aminoglycoside antibiotic isolated from Micromonospora sagamiensis var. nonreducans. Micronomicin is an analog of gentamicin and has broad-spectrum activity against both gram-positive and gram-negative bacteria.
A desoxynojirimycin derivative and inhibitor of alpha-glucosidase with antihyperglycemic activity. Miglitol binds to and inhibits alpha-glucosidase, an enteric enzyme found in the brush border of the small intestines that hydrolyzes oligosaccharides and disaccharides into glucose and other monosaccharides. This prevents the breakdown of larger carbohydrates into glucose and decreases the rise in postprandial blood glucose levels. Compared to acarbose, miglitol is systemically absorbed.
A bisdioxopiperazines analog with antineoplastic activity. Mitinomide inhibits topoisomerase II and slowly promotes DNA-interstrand cross-linking, thereby inhibiting DNA repair, RNA and protein synthesis. This agent acts without increasing topoisomerase II-DNA covalent cleavable complex formation, as do most topoisomerase inhibitors. (NCI04)
An aromatic nitrogen mustard derivative with potential antineoplastic activity. Mitoclomine alkylates DNA and appears to concentrate primarily in the spleen and thymus where it causes lymphocyte depletion.
A prodrug of imidazotetrazine alkylating agent with antineoplastic property. Mitozolomide undergoes ring opening upon the nucleophilic attack at C-4 by an activated molecule of water within the major groove of DNA. The resulting bioactive mono-alkyltriazene species are capable of alkylating nucleophilic residues in the immediate vicinity such as N-7 and/or O-6 sites of guanine, thereby causes intra- or inter-stranded DNA cross-links and trigger apoptosis.
An isoquinoline derivative that is used as a short-acting non-depolarizing agent.
A reversible inhibitor of monoamine oxidase type A; (RIMA); (see MONOAMINE OXIDASE INHIBITORS) that has antidepressive properties.
A linoleic acid derivative with antihyperlipidemic activity.
A benzhydryl acetamide compound, central nervous system stimulant, and CYP3A4 inducing agent that is used in the treatment of NARCOLEPSY and SLEEP WAKE DISORDERS.
A non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, moexipril is hydrolyzed into its active form moexiprilat, which competitively inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the actions of the potent vasoconstrictor angiotensin II and leads to vasodilation. It also prevents angiotensin II-induced aldosterone secretion by the adrenal cortex, thereby promoting diuresis and natriuresis.
A pregnadienediol derivative ANTI-ALLERGIC AGENT and ANTI-INFLAMMATORY AGENT that is used in the management of ASTHMA and ALLERGIC RHINITIS. It is also used as a topical treatment for skin disorders.
A modified form of lipid A, the biologically active part of Gram-negative bacterial lipopolysaccharide (LPS) endotoxin, and a Toll-like receptor 4 (TLR4) agonist, with potential immunostimulatory activity. As a vaccine adjuvant, monophosphoryl lipid A (MPLA) stimulates both cellular and humoral responses to the vaccine antigen. Compared to LPS, MPLA exerts a similar immunostimulatory activity but with reduced toxicity.
A heterocyclic biguanidine with activity against influenza and other viral infections. Although its mechanism of action is not fully known the effects seem to be due to an influence on the virus host-cell system.
The sulfate salt of morphine, an opiate alkaloid isolated from the plant Papaver somniferum and produced synthetically. Morphine binds to and activates specific opiate receptors (delta, mu and kappa), each of which are involved in controlling different brain functions. In the central nervous and gastrointestinal systems, this agent has widespread effects including analgesia, anxiolysis, euphoria, sedation, respiratory depression, and gastrointestinal system smooth muscle contraction.
A glycoprotein that causes regression of MULLERIAN DUCTS. It is produced by SERTOLI CELLS of the TESTES. In the absence of this hormone, the Mullerian ducts develop into structures of the female reproductive tract. In males, defects of this hormone result in persistent Mullerian duct, a form of MALE PSEUDOHERMAPHRODITISM.
A kaempferol with a hydroxyl group at C-3' and -5'.
A chloroethylating nitrosourea that causes DNA cross-linking, inhibiting DNA replication. (NCI)
A synthetic bis-ethyl analogue of spermine with potential antineoplastic activity. N(1),N(11)-bis(ethyl)norspermine (DENSPM), a N-terminally alkylated tetraamine and polyamine mimetics, disrupts polyamine pool homeostasis by modulating the activities of the biosynthetic enzymes, ornithine decarboxylase (ODC), and S-adenosylmethionine decarboxylase (AdoMetDC). This agent also reduces polyamine concentrations through the induction of the catabolic enzyme spermidine/spermine N1-acetyltransferase 1 (SSAT). Polyamines, an integral part of the DNA helix structure, play a critical role in cell division, differentiation and membrane function. Disruption of normal polyamine concentrations by DENSPM may lead to cell growth inhibition.
A polyamine analogue with antiproliferative and potential anti-diarrheal activities. Diethylhomospermine (DEHSPM) antagonizes polyamine activity via NMDA receptor glutamine binding site, thereby modulating inotropic stasis and reducing stool volume (anti-diarrhea). However, due to the toxic effects from metabolites of DEHSP, other tetramine derivatives with less toxicity have been developed.
The trisodium salt of mangafodipir with potential antioxidant and chemoprotective activities. Consisting of manganese (II) ions chelated to fodipir (dipyridoxyl diphosphate or DPDP), mangafodipir scavenges oxygen free radicals such as superoxide anion, hydrogen peroxide, and hydroxyl radical, potentially preventing oxygen free radical damage to macromolecules such as DNA and minimizing oxygen free radical-related chemotoxicity in normal tissues. However, this agent may potentiate the chemotherapy-induced generation of oxygen free radicals in tumor cells, resulting in the potentiation of chemotherapy-induced cytotoxicity; tumor cells, with higher levels of reactive oxygen species than normal cells, possess a lower threshold for oxygen free radical-mediated cytotoxicity. Mangafodipir is traditionally used as an imaging agent in magnetic resonance imaging (MRI).
A yellow colored, combustible leaflet material that emits toxic fumes of nitrogen oxides when heated to decomposition. Michler's base is used as a chemical intermediate in the manufacture of dyes and for its hydrochloric salt and is also used as an analytical reagent in the determination of lead. Exposure to Michler's base irritates the skin and eyes and can lead to methemoglobinemia and respiratory tract distress. Michler's base is reasonably anticipated to be a human carcinogen. (NCI05)
The N-alkylated analogue of the anthracycline antineoplastic antibiotic daunomycin. N,N-Dibenzyl Daunomycin interacts with topoisomerase II, thereby inhibiting DNA replication and repair and promoting DNA fragmentation. This agent is less cardiotoxic than daunomycin. (NCI04)
A methylated derivative of L-arginine that is a competitive inhibitor of nitric oxide synthase (NOS). Asymmetric dimethylarginine (ADMA) is formed when S-adenosylmethionine protein N-methyltransferases transfer methyl groups from S-adenosylmethionine to arginine. Free ADMA in plasma competes with the L-arginine for binding to the heme in NOS and inhibits nitric oxide (NO) synthesis. Decreased synthesis of NO inhibits vasodilation and leads to endothelial dysfunction. Elevated plasma levels of ADMA are seen in certain types of cancer, cardiovascular disease, hypertension, hyperlipidemia, type 2 diabetes mellitus, and increased oxidative stress.
A synthetic phenylretinamide analogue of retinol (vitamin A) with potential antineoplastic and chemopreventive activities. Carboxyphenyl retinamide induces cell differentiation and inhibits tumor cell growth and carcinogenesis. This agent may also induce cell cycle arrest in the G1 phase in some cancer cell types. (NCI04)
An orally- and topically-active alkyl-phosphocholine compound with potential antineoplastic activity. Miltefosine targets cellular membranes, modulating cell membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis. As an immunomodulator, miltefosine stimulates T-cells, macrophages and the expression of interleukin 3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and interferon gamma (INF-gamma). (NCI04)
A synthetic cannabinoid and dibenzopyrane derivative with anti-emetic activity. Although the mechanism of action has not been fully elucidated yet, it has been suggested that nabilone is a highly selective and strong agonist for the cannabinoid receptors CB1 and CB2, both of which are coupled to Gi/o proteins. The CB1 receptors are expressed predominantly in central and peripheral neurons and receptor stimulation has been implicated in the reduction of chemotherapy-induced nausea.
A butanone non-steroidal anti-inflammatory drug and cyclooxygenase-2 (COX2) inhibitor that is used in the management of pain associated with OSTEOARTHRITIS and RHEUMATOID ARTHRITIS.
A topical, synthetic allylamine derivate similar to terbinafine with broad-spectrum antifungal activity. Naftifine can be fungicidal or fungistatic depending on the concentration and the organisms involved.
Decanoic acid ester of nandrolone that is used as an anabolic agent to prevent or treat WASTING SYNDROME associated with severe chronic illness or HIV infection (HIV WASTING SYNDROME). It may also be used in the treatment of POSTMENOPAUSAL OSTEOPOROSIS.
A flavanone with hydroxyl groups at C-5, C-7, and C-4'.
A flavonoid comprised of the flavanone naringenin and the disaccharide rutinose.
A beta-1 adrenergic receptor antagonist with antihypertensive and vasodilatory activity. Nebivolol binds to and blocks the beta-1 adrenergic receptors in the heart, thereby decreasing cardiac contractility and rate. This leads to a reduction in cardiac output and lowers blood pressure. In addition, nebivolol potentiates nitric oxide (NO), thereby relaxing vascular smooth muscle and exerting a vasodilatory effect.
A pyranoquinolone derivative that inhibits activation of inflammatory cells which are associated with ASTHMA, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets.
A drug used to treat depression. It belongs to the family of drugs called antidepressant agents.
A colorless, volatile and highly flammable, liquid inorganic compound with a characteristic, musty odor that emits toxic carbon monoxide fumes upon heating. Nickel carbonyl is primarily used for nickel coatings and to manufacture high-purity nickel powder. Exposure to this substance can cause severe dermatitis, skin and asthma-like allergies and affects the lungs, kidneys, gastrointestinal tract and neurological system. Nickel carbonyl is a known carcinogen and is associated with an increased risk of developing lung and nasal cancers. (NCI05)
A yellow, green or blue colored, crystalline inorganic compound that produces toxic gases upon heating. Nickel sulfate is used in electroplating and as a chemical intermediate to produce other nickel compounds. Exposure to this substance can cause severe dermatitis, skin and asthma-like allergies and affects the lungs, kidneys, gastrointestinal tract and neurological system. Nickel sulfate is a known carcinogen and is associated with an increased risk of developing lung and nasal cancers. (NCI05)
A niacin derivative with antilipidemic activity.
A derivative of the NIACINAMIDE that is structurally combined with an organic nitrate. It is a potassium-channel opener that causes vasodilatation of arterioles and large coronary arteries. Its nitrate-like properties produce venous vasodilation through stimulation of guanylate cyclase.
A synthetic, nonsteroidal agent with antiandrogenic properties. Nilutamide preferentially binds to androgen receptors and blocks androgen receptor activation by testosterone and other androgens; this agent may inhibit androgen-dependent growth of normal and neoplastic prostate cells. (NCI04)
A synthetic benzamide with antiprotozoal activity. Nitazoxanide exerts its antiprotozoal activity by interfering with the pyruvate ferredoxin/flavodoxin oxidoreductase dependent electron transfer reaction, which is essential to anaerobic energy metabolism. PFOR enzyme reduces nitazoxanide, thereby impairing the energy metabolism. However, interference with the PFOR enzyme-dependent electron transfer reaction may not be the only pathway by which nitazoxanide exhibits antiprotozoal activity. Nitazoxanide is active against Giardia lamblia and Cryptosporidium parvum.
An amino acid derivative and nitric oxide synthase (NOS) inhibitor with potential antineoplastic and antiangiogenic activities. Upon administration, NG-nitro-L-arginine inhibits the enzyme nitric oxide synthase, thereby preventing the formation of nitric oxide (NO). By preventing NO generation, the vasodilatory effects of NO are abrogated leading to vasoconstriction, reduction in vascular permeability and an inhibition of angiogenesis. As blood flow to tumors is restricted, this may result in an inhibition of tumor cell proliferation. NO plays an important role in tumor blood flow and stimulation of angiogenesis, tumor progression, survival, migration and invasiveness.
A nipecotic acid derivative that acts as a GABA uptake inhibitor and anticonvulsant agent. It is used in the treatment of EPILEPSY, for refractory PARTIAL SEIZURES.
Nonionic surfactant mixtures varying in the number of repeating ethoxy (oxy-1,2-ethanediyl) groups. They are used as detergents, emulsifiers, wetting agents, defoaming agents, etc. Nonoxynol-9, the compound with 9 repeating ethoxy groups, is a spermatocide, formulated primarily as a component of vaginal foams and creams.
Acetate ester of norethindrone that is used as a long-term contraceptive.
A stable transition state analogue for an aspartate transcarbamylase-catalyzed reaction with antineoplastic activity. Sparfosic acid is a stable transition analogue of the activated complex for the reaction catalyzed by aspartate transcarbamylase, the first step in the pyrimidine biosynthetic pathway. This agent inhibits de novo pyrimidine biosynthesis and increases the extent to which fluorouracil metabolites are incorporated into RNA.
A commercial combination preparation, by Vicks, containing acetaminophen, dextromethorphan hydrobromide and doxylamine succinate used to relieve symptoms of cold and flu. Acetaminophen exerts analgesic and antipyretic actions by inhibiting prostaglandin synthesis. Dextromethorphan exerts antitussive activity by raising the threshold for coughing in the cough center. Doxylamine succinate, an antihistamine, blocks the effects of histamine, thereby treating symptoms such as sneezing, itchy, watery eyes, runny nose, itchy throat and causes drowsiness.
A white, crystalline powder that is very unstable in the presence of light but fairly heat resistant. Ochratoxin A is a widespread, naturally occurring mycotoxin that is produced by some fungi, especially by Aspergillus and Penicillium, and is a very common food contaminant found on grains, coffee beans, nuts, decaying vegetation, moldy cereals and animal feeds. This toxin is used in research as an experimental teratogen and carcinogen. Ochratoxin A is reasonably anticipated to be a human carcinogen and may be associated with an increased risk of developing urinary tract tumors. (NCI05)
An amphiphilic piperidine agent shown to reduce plaque formation in vitro and to reduce gingivitis in vivo in an animal model.
An acyl-Coenzyme A:cholesterol acyltransferase (ACAT) inhibitor with antilipidemic, antiatherosclerotic, and antithrombotic activity. In an animal model, inhibition of ACAT by octimibate increased HDL receptor activity and stimulated HDL-mediated cholesterol efflux from peritoneal macrophages.
A lipid soluble cardiac glycoside with potential antineoplastic activity. Upon administration, oleandrin specifically binds to and inhibits the alpha3 subunit of the Na/K-ATPase pump in human cancer cells. This may inhibit the phosphorylation of Akt, upregulate MAPK, inhibit NF-kb activation and inhibit FGF-2 export and may downregulate mTOR thereby inhibiting p70S6K and S6 protein expression. All of this may lead to an induction of apoptosis. As cancer cells with relatively higher expression of the alpha3 subunit and with limited expression of the alpha1 subunit are more sensitive to oleandrin, one may predict the tumor response to treatment with lipid-soluble cardiac glycosides such as oleandrin based on the tumors Na/K-ATPase pump protein subunit expression. Overexpression of the alpha3 subunit in tumor cells correlates with tumor proliferation.
A prodrug of mesalamine (5-Aminosalicylic acid; 5-ASA) with anti-inflammatory activity. Unabsorbed olsalazine passes through gastrointestinal tract and is cleaved by azoreductases, produced by microflora in colon, into 2 active molecules of 5-ASA. 5-ASA exerts its anti-inflammatory action locally by inhibiting cyclooxygenase and lipoxygenase activities, thereby reducing the production of prostaglandins and leukotrienes. In addition, mesalamine may act as a scavenger of reactive oxygen free radicals.
A synthetic dithiolethione with potential chemopreventive and anti-angiogenic properties. Oltipraz induces phase II detoxification enzymes, such as glutathione S transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1). The induction of detoxification enzymes enhances the detoxification of certain cancer-causing agents, thereby enhancing their elimination and preventing carcinogen-induced DNA damages. Although the exact mechanism through which the anti-angiogenesis effect remains to be fully elucidated, oltipraz maybe able to modulate the expression of a number of angiogenic factors, thereby blocking the sustained and focal neovascularization in multiple tumor cell types.
An amino acid derivative with potential antineoplastic activity. NG-monomethyl-L-arginine inhibits the enzyme nitric oxide synthase, resulting in a diminution of nitrous oxide production. This agent may inhibit tumor angiogenesis. (NCI04)
A topical imidazole derivative with antifungal activity against Candida albicans, Malassezia furfur and dematophytes.
Protein E7 (98 aa, ~11 kDa) is encoded by the human papillomavirus type 16 E7 gene. This protein is involved in the modulation of the activity of both retinoblastoma protein and histone deacetylases in the infected host cell, which is associated with viral genome replication and host cell transformation.
Oncostatin-M (252 aa, ~28 kDa) is encoded by the human OSM gene. This protein plays a role in the regulation of cytokine production, the modulation of cell proliferation and the development and regeneration of the liver.
A quinolinone derivative with anti-ulcer and anti-inflammatory activities. Rebamipide induces cyclooxygenase 2 (COX2) synthesis which results in an increase in endogenous prostaglandin synthesis in the gastric mucosa. This agent also inhibits H. pylori-induced production of tumor necrosis factor (TNF) alpha and subsequent inflammation of the gastric mucosa. In addition, rebamipide scavenges oxygen-derived free radicals that potentially cause mucosal injury, and stimulates prostaglandin EP4 receptor gene expression followed by mucous secretion, thereby enhancing the gastric mucosal defense.
The bromide salt form of rocuronium, an intermediate-acting quaternary aminosteroid with muscle relaxant property. Rocuronium bromide competitively binds to the nicotinic receptor at the motor end plate, and antagonizes acetylcholine binding, which results in skeletal muscle relaxation and paralysis.
A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent.
An organoplatinum complex in which the platinum atom is complexed with 1,2-diaminocyclohexane (DACH) and with an oxalate ligand as a 'leaving group.' A 'leaving group' is an atom or a group of atoms that is displaced as a stable species taking with it the bonding electrons. After displacement of the labile oxalate ligand leaving group, active oxaliplatin derivatives, such as monoaquo and diaquo DACH platinum, alkylate macromolecules, forming both inter- and intra-strand platinum-DNA crosslinks, which result in inhibition of DNA replication and transcription and cell-cycle nonspecific cytotoxicity. The DACH side chain appears to inhibit alkylating-agent resistance. (NCI04)
An anthrapyrazole antineoplastic antibiotic. Piroxantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. Although less cardiotoxic than doxorubicin, this agent exhibits a narrow spectrum of antineoplastic activity. (NCI04)
A nonsteroidal anti-inflammatory drug (NSAID) derivative of oxazole-propionic acid with analgesic and antipyretic properties. As a first generation NSAID inhibitor, oxaprozin binds to and inactivates both isoforms of cyclooxygenase (COX-1 and-2), thereby blocking the conversion of arachidonic acid to pro-inflammatory prostaglandins. When inhibiting COX-2, this agent may be effective in relieving pain and inflammation; when inhibiting COX-1, it may produce unacceptable gastrointestinal side effects. (NCI04)
A carbamazepine derivative that acts as a voltage-gated sodium channel blocker. It is used for the treatment of PARTIAL SEIZURES with or without secondary generalization. It is also an inducer of CYTOCHROME P-450 CYP3A4.
A broad spectrum imidazole derivative with antifungal activity. Although the exact mechanism of action has yet to be fully elucidated, oxiconazole, like other azole antifungals, most likely inhibits the cytochrome P450-dependent demethylation of lanosterol. This prevents the synthesis of ergosterol which is a crucial component of fungal cell membrane. By disrupting fungal cell membrane synthesis and integrity, oxiconazole alters fungal cell membrane permeability, promotes loss of essential intracellular components and eventually inhibits fungal cell growth.
A benzophenone derivative used as a sunscreen agent. Oxybenzone absorbs UVB and UVA II rays, resulting in a photochemical excitation and absorption of energy. Upon return to ground state, the absorbed energy results in emission of longer wavelength radiation and decreased skin penetration of radiation which reduces the risk of DNA damage.
A tertiary amine possessing antimuscarinic and antispasmodic properties. Oxybutynin blocks muscarinic receptors in smooth muscle, hence inhibiting acetylcholine binding and subsequent reduction of involuntary muscle contractions. Oxybutynin is used to reduce bladder contractions by relaxing bladder smooth muscle.
A synthetic tertiary amine and antimuscarinic agent with antispasmodic and antisecretory activities. Oxyphencyclimine binds to and blocks the muscarinic receptor on smooth muscle. This agent has a direct relaxing effect on smooth muscle and therefore prevents spasms in the muscles of the gastrointestinal tract, inhibits gastrointestinal propulsive motility, decreases gastric acid secretion and controls excessive pharyngeal, tracheal and bronchial secretion.
A loop diuretic and active metabolite of its prodrug etozoline. Ozolinone was never marketed.
A natural homologue of ribonuclease A isolated from the eggs of the frog Rana pipiens. Ranpirnase primarily degrades cellular transfer RNA with a substrate specificity for uridine-guanidine base-pair sequences, resulting in inhibition of protein synthesis and cytotoxicity. This agent also activates caspase-9 in mitochondria, resulting in tumor cell apoptosis. (NCI04)
Nutritive oil extracted from the fleshy mesocarp of the fruit of the African palm tree, Elaeis guineensis.
A isoquinoline alkaloid from amaryllis with antineoplastic activity.
A benzothiadiazine sulfonamide belonging to the class of the thiazide diuretics.
A polypeptide that consists of the 1-34 amino-acid fragment of human PARATHYROID HORMONE, the biologically active N-terminal region. The acetate form is given by intravenous infusion in the differential diagnosis of HYPOPARATHYROIDISM and PSEUDOHYPOPARATHYROIDISM. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
A serotonin uptake inhibitor that is effective in the treatment of depression.
A chloroethylnitrosourea compound and an alkylating agent with antineoplastic property. PCNU inhibits DNA synthesis by alkylating DNA and causing DNA cross links, thereby inducing apoptosis. In addition, this agent may be associated with pulmonary, hepatic, and hematologic toxicities. Unlike other nitrosoureas, PCNU has strong alkylating while weak carbamoylating activity.
A ticlopidine analog and platelet purinergic P2Y receptor antagonist that inhibits adenosine diphosphate-mediated PLATELET AGGREGATION. It is used to prevent THROMBOEMBOLISM in patients with ARTERIAL OCCLUSIVE DISEASES; MYOCARDIAL INFARCTION; STROKE; or ATRIAL FIBRILLATION.
An antifungal agent isolated from Paecilomyces varioti Bainier var. antibioticus with topical activity against common dermatophytes.
A polysaccharide in which a) galacturonic acid is a primary monomer (Polygalacturonan), b) L-rhamnose and D-galacturonic acid monomers alternate (Rhamnogalacturonan I), and c) various monosaccharides occur branched and complex (Rhamnogalacturonan II).
A naturally-occurring saturated fatty acid with nine carbon atoms. The ammonium salt form of nonanoic acid is used as an herbicide. It works by stripping the waxy cuticle of the plant, causing cell disruption, cell leakage, and death by desiccation.
A derivative of bromoacrylic acid with cytostatic activity. Although the mechanism of action is unclear, penberol might inhibit tumor growth mediated through inhibition of the cell energetic metabolism.
A synthetic derivative of pyrimidine with antineoplastic activity. Penclomedine alkylates and crosslinks DNA, resulting in DNA strand breaks and inhibition of DNA and RNA synthesis. This agent is more active against tumor cells that are defective in p53 function. (NCI04)
A principal metabolite of hexamethylmelamine with antineoplastic activity. Pentamethylmelamine alkylates DNA and other macromolecules and forms DNA intrastrand and DNA-protein crosslinks, thereby preventing DNA replication. (NCI04)
The essential oil extracted from the leaves of Mentha x piperita. Peppermint oil is used for its aromatic properties and as a flavoring and to treat illnesses of the digestive and respiratory system as well as pain.
A non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Perindoprilat inhibits ACE and, thus, the conversion of angiotensin I to angiotensin II; consequently, angiotensin II-mediated vasoconstriction and angiotensin II-stimulated aldosterone secretion from the adrenal cortex are inhibited and diuresis and natriuresis ensue.
A pyrethroid insecticide commonly used in the treatment of LICE INFESTATIONS and SCABIES.
A steroidal nitrogen mustard with antineoplastic and mutagenic activities. After attachment to cell-surface steroid receptors and uptake, phenesterin enters the nucleus where it alkylates macromolecules, resulting in decreased cell proliferation. (NCI04)
An isothiocyanate found in cruciferous vegetables with chemopreventive and potential antitumor activities. Although the mechanism of action is unclear, phenethyl Isothiocyanate (PEITC) was shown to induce apoptosis in tumor cells, possibly mediated through its metabolic intermediates, reactive oxygen species (ROS). PEITC also is able to activate ERK and JNK signal transduction, which in turn induces expression of stress-responsive genes. Specifically, this agent has been shown to reactivate gene expression of a detoxification enzyme, glutathione S-transferase that is silenced in prostate carcinoma.
An antiseptic and disinfectant aromatic alcohol.
An antipyrine derivative that functions as a free radical scavenger and neuroprotective agent. It is used in the treatment of AMYOTROPHIC LATERAL SCLEROSIS and STROKE.
An ethanolamine derivative with antihistaminic property. Phenyltoloxamine blocks H1 histamine receptors, thereby inhibiting phospholipase A2 and production of endothelium-derived relaxing factor, nitric oxide. Subsequent lack of activation of guanylyl cyclase through nitric oxide results in decreased cyclic GMP levels, thereby inhibiting smooth muscle constriction of various tissues, decreasing capillary permeability and decreasing other histamine-activated allergic reactions.
A short-acting barbiturate derivative without hypnotic properties, Phetharbital (N-phenylbarbital) can be used as a sedative and anticonvulsant agent due to its mechanism of enhancing GABA (Gamma Amino Butyric Acid) transmission and inhibition of synaptic excitation. Phetharbital has generally been withdrawn from clinical use. (NCI04)
A synthetic organic analog of inorganic pyrophosphate with activity against several types of viruses, but primarily used for the treatment of cytomegalovirus retinitis. Foscarnet selectively blocks the pyrophosphate binding site of virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. Because this agent crosses the blood brain barrier, it may be used in the treatment of viral infections of the central nervous system.
A broad spectrum antimicrobial agent. Phthalylsulfathiazole is used in the treatment of dysentery, colitis, and gastroenteritis.
Compounds from plant sources with estrogen-like activities
A guanidine that opens POTASSIUM CHANNELS producing direct peripheral vasodilatation of the ARTERIOLES. It reduces BLOOD PRESSURE and peripheral resistance and produces fluid retention. (Martindale The Extra Pharmacopoeia, 31st ed)
A thiazolidinedione and PPAR GAMMA agonist that is used in the treatment of TYPE 2 DIABETES MELLITUS.
A piperazinyl androstane derivative which is a non-depolarizing neuromuscular blocking agent (NEUROMUSCULAR NONDEPOLARIZING AGENTS). It is used as a muscle relaxant during ANESTHESIA and surgical procedures.
A natural estrogenic substance composed of estrone sulfate and piperazine. Estropipate diffuses through the cell membrane and binds to and subsequently activates the nuclear estrogen receptor found in the reproductive tract, breast, pituitary, hypothalamus, liver, and bone. The activated complex binds to the estrogen response element on the DNA and activates the transcription of genes involved in the functioning of the female reproductive system and secondary sex characteristics.
A short-acting, beta-adrenergic receptor agonist with bronchodilator activity. Pirbuterol selectively binds to beta-2 adrenergic receptors in bronchial smooth muscle, thereby activating intracellular adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, relieve bronchospasms, improve mucociliary clearance and inhibit the release of mediators of immediate hypersensitivity from cells, especially from mast cells.
A sulfamoylbenzoic acid belonging to the class of loop diuretics. Piretanide is structurally related to furosemide and bumetanide.
A fibrate agent with antilipidemic activity.
A derivative of clindamycin with a 6-membered ring replacing clindamycin's 5-membered ring. Compared to clindimycin, pirlimycin has increased activity against gram-positive bacteria, including Staphylococcus aureus and coagulase negative species of Staphylococcus and Streptococcus. This agent is primarily used in the treatment of mastitis in cattle.
A nicotinic acid derivative with antilipidemic activity.
An acyl derivative of morpholinomethylurea (MMU) with clofibric acid with antihyperlipidemic activity. In trials plafibride showed better gastric tolerance and a lower incidence of adverse events than did clofibrate.
A dihydropyridine calcium channel blockers with antihypertensive and vasodilator activities. Isradipine blocks the calcium entry through the calcium ion channels of coronary and peripheral vascular smooth muscle, thereby dilating coronary arteries and peripheral arterioles. This increases oxygen delivery due to an increased blood flow and reduces oxygen requirements due to decrease in total peripheral resistance. (NCI05)
An alkyl polyglycol ether of LAURYL ALCOHOL, chemically defined as an alcohol ethoxylate having an average alkyl chain of 12-14 carbon atoms, and an ethylene oxide chain of 9 ethylene oxide units. It is used as a detergent, and medically as a local anesthetic, and as a sclerosing agent for the treatment of ESOPHAGEAL AND GASTRIC VARICES and VARICOSE VEINS.
A synthetic complex of carboxymethylcellulose, polyinosinic-polycytidylic acid, and poly-L-lysine double-stranded RNA. Poly ICLC may stimulate the release of cytotoxic cytokines and, by inducing interferon-gamma production, may increase the tumoricidal activities of various immunohematopoietic cells. (NCI04)
Hydrocarbons that contain more than one triple bond; or an oxidized form of POLYENES.
A synthetic long-acting polymer derivative of the female sex hormone estradiol. As the primary, most potent estrogen hormone produced by the ovaries, estradiol binds to and activates specific nuclear receptors. Estradiol exhibits mild anabolic and metabolic properties, and increases blood coagulability. Administration of polyestradiol phosphate leads to the marked decrease of testosterone levels and may exhibit a bone mass-preserving effect in patients with prostatic cancer. (NCI04)
A dual function enzyme derived from bacterial Acinetobacter glutaminasificans used as an adjuvant in chemotherapy. Acinetobacter glutaminase-asparaginase (AGA) possesses both L-glutaminase and L-asparaginase activities, capable of hydrolyzing glutamine and asparagine, thereby disturbing nitrogen supplies for dividing cells. When co-administered with alkylating agent melphalan, which utilizes amino acid transport systems for cellular uptake, depletion of glutamine by AGA appeared to facilitate melphalan uptake and enhance its cytotoxicity.
A complex of polyethylene glycol conjugated with L-asparaginase. Asparaginase hydrolyzes L-asparagine to L-aspartic acid and ammonia, thereby depleting these cells of asparagine and blocking protein synthesis and tumor cell proliferation, especially in the G1 phase of the cell cycle. The agent also induces apoptosis in tumor cells. Pegylation decreases the enzyme's antigenicity. Asparagine is critical to protein synthesis in leukemic cells, which cannot synthesize this amino acid due to the absence of the enzyme asparagine synthase. (NCI04)
A large class of organic compounds having more than one PHENOL group.
A highly negative-charged carbohydrate composed of a linear polymer of alpha 2,8-linked sialic acid residue with potential immunotherapeutic activity. Polysialic acid (PSA) is mainly attached to the neural cell adhesion molecule (NCAM), a membrane-bound glycoprotein overexpressed in certain types of cancers. In embryonic tissue PSA-NCAM is abundantly expressed and PSA plays an important role in formation and remodeling of the neural system through modulation of the adhesive properties of NCAM, thereby reducing cell-cell interactions and promoting cellular mobility. In adult tissue however, the expression of PSA-NCAM is associated with a variety of malignant tumors, signifying its potential role in tumor metastasis. When administered in a vaccine formulation, PSA may stimulate a cytotoxic T cell response against tumors expressing PSA, thereby resulting in a reduction in tumor size.
An extracellular cystatin subtype that is abundantly expressed in bodily fluids. It may play a role in the inhibition of interstitial CYSTEINE PROTEASES.
A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparation of some drugs.
A crystalline salt, KNO3; a strong oxidizer used especially in making gunpowder, as a fertilizer, and in medicine.
The potassium salt of perchloric acid and a member of the Hofmeister ions series with thyroid blocking properties. Potassium perchlorate is a competitive inhibitor of iodine uptake through inhibiting the sodium-iodide symporter (NIS) on the thyroid follicular cell membrane. This results in a potential decrease in thyroid hormone synthesis including thyroxine (T4) and tri-iodothyronine (T3). In addition, this agent decreases the accumulation of the radioactive imaging substance and Hofmeister series ion, pertechnetate Tc 99m, in the choroid plexus and in the salivary and thyroid glands through competitive displacing.
An inorganic compound used as a laxative, dietary supplement and for electrolyte-replacement purposes. Phosphate, a predominant intracellular anion, plays an important role in energy storage, osteoblastic and osteoclastic activities, regulating serum calcium concentrations and numerous cellular phosphate-transfer reactions. Potassium phosphate increases fluidity of the intestinal contents by retention of water by osmotic forces, thereby indirectly inducing intestinal smooth muscle constriction.
A morpholine derivative with local anesthetic property. Pramocaine decreases the permeability of the neuronal membrane to sodium ions by reversibly binding to and inhibiting voltage-gated sodium channels. This results in stabilization of the membrane and, thereby inhibiting the ionic fluxes required for membrane depolarization, hence resulting in the failure to initiate a propagated action potential and subsequent conduction blockade.
A synthetic non-halogenated double-ester derivative of the corticosteroid prednisolone with anti-inflammatory, antipruritic and vasoconstrictive properties. Following skin permeation, prednicarbate enters cells and binds to and activates specific nuclear receptors, resulting in an altered gene expression and inhibition of pro-inflammatory cytokine production by increasing the expression of lipocortins. These block phospholipase A-dependent release of arachidonic acid thereby inhibiting prostaglandin synthesis. This agent also decreases the number of circulating lymphocytes by suppression of the production of vasodilators such as prostacyclin and nitric oxide.
The acetate salt form of prednisolone, a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. As a glucocorticoid receptor agonist, prednisolone acetate binds to specific intracellular glucocorticoid receptors, and causes the ligand-receptor complex to be translocated to the nucleus where it initiates the transcription of glucocorticoid-responsive genes such as various cytokines and lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both potent mediators of inflammation. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis in sensitive tumor cell populations.
Combination of imipenem and cilastatin that is used in the treatment of bacterial infections; cilastatin inhibits renal dehydropeptidase I to prolong the half-life and increase the tissue penetration of imipenem, enhancing its efficacy as an anti-bacterial agent.
A natural or synthetic isoprenoid hydrocarbon (C19) derivative, Pristane is commonly used in research to prime the abdomen prior to hybridoma implantation in experimental animals. An irritant that induces granulomatous inflammation and interferes with local lymphatic drainage, it increases ascitic yields. Pristane has a low margin of safety and is toxic at levels slightly higher than used to prime animals. (NCI04)
A class of tannins which are composed of two or more flavan-3-ol units with multiple hydroxyl groups.
A long-acting beta-2-adrenergic receptor agonist.
The potassium salt form of prorenoate, a steroidal aldosterone antagonist with potassium-sparing diuretic activity. Prorenoate antagonizes the activity of aldosterone at the mineralocorticoid receptor in the nephron and thereby prevents sodium reabsorption. This interferes with the sodium/potassium exchanger and causes sodium and water excretion while reducing potassium excretion.
A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations.
An eicosanoid that is generated by the action of cyclooxygenases on the omega-3 fatty acid eicosapentaenoic acid (EPA). Prostaglandin E3 regulates ocular pressure, exerts anti-inflammatory activities and may inhibit tumor cell proliferation. Prostaglandin E3 may be used as a biomarker for EPA to evaluate the association between EPA and its antineoplastic activity.
Interferon-induced DYNAMIN-like GTP-binding proteins localized in the cytoplasm, nuclear pore complex and nucleus. They play a role in antiviral defense and immunity.
A tetrapyrrole containing 4 methyl, 2 propionic and 2 vinyl side chains that is a metabolic precursor for hemes, cytochrome c and chlorophyll. Protoporphyrin IX is produced by oxidation of the methylene bridge of protoporphyrinogen by the enzyme protoporphyrinogen oxidase.
A methylxanthine and derivative of theophylline. Proxyphylline relaxes smooth muscles, particularly bronchial muscles. This xanthine most likely exerts its effect by inhibiting cAMP or cGMP phosphodiesterases, thereby increasing levels of the second messenger cAMP or cGMP intracellularly. Other mode of actions include an adenosine antagonistic effect on the activity of CD4 lymphocytes and mediator release from mast cells thereby decreasing lung sensitivity to allergens and other substances that cause inflammation. Proxyphylline also acts as a CNS stimulant and exerts a positive chronotropic and inotropic effect on the heart.
A protein-bound polysaccharide derived from the mushroom Trametes versicolor (Turkey Tail) with immunoadjuvant and potential antitumor activities. Although its mechanism of action has yet to be fully elucidated, in vitro and in vivo studies indicate that polysaccharide-K induces peripheral blood monocyte secretion of IL-8 and TNF-alpha, induces T cell proliferation, and prevents cyclophosphamide-induced immunosuppression. This agent has also been reported to stimulate macrophages to produce reactive nitrogen intermediates and superoxide anions and to promote apoptosis in the promyelocytic leukemia cell line HL-60.
A synthetic, pyrimidine C-5 nucleoside with antineoplastic activity. Pseudoisocytidine, after conversion into pseudoisocytidine triphosphate, is incorporated into DNA and RNA eventually halting tumor cell proliferation. Compared to 5-azacytidine and cytarabine, this agent shows enhanced stability and resistance to enzymatic deamination.
A crystalline conjugate of folic acid, having general properties of a polypeptide. Pteropterin differs from folic acid in that it consists of three molecules of glutamic acid instead of one. Pteropterin can potentially be used as an antimetabolite in the treatment of cancer.
A congener of pyridine 2-diazohydroxide. Pyrazine diazohydroxide forms DNA adducts via the reactive pyrazine diazonium ion, thereby inhibiting DNA synthesis. (NCI04)
A nucleoside analog. Pyrazofurin potently inhibits orotidine 5'-monophosphate (OMP) decarboxylase, thereby interfering with de novo synthesis of uridine nucleotides and resulting in cytotoxicity. This agent also causes a rapid depletion of the pyrimidine deoxynucleotide pool, thereby inhibiting DNA synthesis and cell replication. (NCI04)
A fungistatic and antimicrobial derivative of aspergillic acid. Although the exact mechanism of action remains to be fully elucidated, pyrithione appears to interfere with membrane transport ultimately leading to a loss of metabolic control.
saturated 5-membered ring structure with one nitrogen heteroatom.
An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed)
A synthetic benzodiazepine derivative with anxiolytic, sedative and hypnotic properties. Quazepam and its major metabolite 2-oxoquazepam potentiate gamma-aminobutyric acid (GABA) activity by binding to the benzodiazepine-1 recognition site (BZ-1) within the GABA-A receptor, located in the limbic, neocortical and mesencephalic reticular system. This increases the frequency of GABA-activated chloride channel opening events, allowing the flow of chloride ions into the neuron leading to membrane hyperpolarization and decreased neuronal excitability.
A prodrug and non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Quinapril is hydrolized into its active form quinaprilat, which binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This abolishes the potent vasoconstrictive actions of angiotensin II and leads to vasodilatation. Quinapril also causes a decrease in angiotensin II-induced aldosterone secretion by the adrenal cortex, thereby promoting diuresis and natriuresis, and increases bradykinin levels.
The gluconate salt form of quinidine, an alkaloid with antimalarial and antiarrhythmic (Class la) properties. Quinidine gluconate exerts its anti-malarial activity by acting primarily as an intra-erythrocytic schizonticide through association with the hemepolymer (hemozoin) in the acidic food vacuole of the parasite thereby preventing further polymerization by heme polymerase enzyme. This results in accumulation of toxic heme and death of the parasite. Quinidine gluconate exerts its antiarrhythmic effects by depressing the flow of sodium ions into cells during phase 0 of the cardiac action potential, thereby slowing the impulse conduction through the atrioventricular (AV) node, reducing the maximal rate of phase 0 depolarization and prolonging the refractory period. Quinidine gluconate also reduces the slope of phase 4 depolarization in Purkinje-fibres resulting in slowed conduction and reduced automaticity in the heart.
A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed)
A substituted benzamide that has antipsychotic properties. It is a dopamine D2 receptor (see RECEPTORS, DOPAMINE D2) antagonist.
A non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Ramiprilat inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and leads to vasodilation. This agent also causes an increase in bradykinin levels and a decrease in angiotensin II-induced aldosterone secretion by the adrenal cortex, thereby promoting diuresis and natriuresis.
A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat.
An antipsychotic agent that is specific for dopamine D2 receptors. It has been shown to be effective in the treatment of schizophrenia.
A potent angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Rentiapril competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Rentiapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A naturally occurring capsaicin analog found in the latex of the cactus Euphorbia resinifera with analgesic activity. Resiniferatoxin (RTX) binds to and activates the transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel in the plasma membrane of primary afferent sensory neurons. This increases the permeability to cations, and leads to an influx of calcium and sodium ions. This results in membrane depolarization, causing an irritant effect, followed by desensitization of the sensory neurons thereby inhibiting signal conduction in afferent pain pathways and causing analgesia. TRPV1, a member of the transient receptor potential channel (TRP) superfamily, is a heat- and chemo-sensitive calcium/sodium ion channel that is selectively expressed in a subpopulation of pain-sensing primary afferent neurons.
A phytoalexin derived from grapes and other food products with antioxidant and potential chemopreventive activities. Resveratrol induces phase II drug-metabolizing enzymes (anti-initiation activity); mediates anti-inflammatory effects and inhibits cyclooxygenase and hydroperoxidase functions (anti-promotion activity); and induces promyelocytic leukemia cell differentiation (anti-progression activity), thereby exhibiting activities in three major steps of carcinogenesis. This agent may inhibit TNF-induced activation of NF-kappaB in a dose- and time-dependent manner. (NCI05)
A naturally-occurring fatty acid ester form of retinol (vitamin A) with potential antineoplastic and chemopreventive activities. Retinyl acetate binds to and activates retinoid receptors, inducing cell differentiation and decreasing cell proliferation. This agent also inhibits carcinogen-induced neoplastic transformation in some cancer cell types and exhibits immunomodulatory properties. (NCI04)
A naturally-occurring phenyl analogue of retinol (vitamin A) with potential antineoplastic and chemopreventive activities. As the most common form of vitamin A taken for dietary supplementation, retinyl palmitate binds to and activates retinoid receptors, thereby inducing cell differentiation and decreasing cell proliferation. This agent also inhibits carcinogen-induced neoplastic transformation, induces apoptosis in some cancer cell types, and exhibits immunomodulatory properties. (NCI04)
A macrocyclic lactone. Rhizoxin binds to tubulin and inhibits microtubule assembly, thereby inducing cytotoxicity. This agent also may inhibit endothelial cell-induced angiogenic activity, which may result in decreased tumor cell proliferation. (NCI04)
Immunizing agent containing IMMUNOGLOBULIN G anti-Rho(D) used for preventing Rh immunization in Rh-negative individuals exposed to Rh-positive red blood cells.
An orally available prodrug of ribavirin, a synthetic nucleoside analog of ribofuranose with activity against a wide range of viruses, especially the hepatitis C virus and influenza virus. Taribavirin is converted into ribavirin, which is incorporated into viral nucleic acid, thereby inhibiting viral RNA synthesis, inducing viral genome mutations, and inhibiting normal viral replication.
A synthetic rifamycin derivative and anti-bacterial agent that is used for the treatment of GASTROENTERITIS caused by ESCHERICHIA COLI INFECTIONS. It may also be used in the treatment of HEPATIC ENCEPHALOPATHY.
A benzothiazole derivative with neuroprotective and potential anti-depressant and anxiolytic activities. While the mechanism of action of riluzole is unknown, its pharmacological activities in motor neurons include the following, some of which may be related to its effect: 1) an inhibitory effect on glutamate release, 2) inactivation of voltage-dependent sodium channels, and 3) interference with intracellular events that follow transmitter binding at excitatory amino acid receptors. In animal models, this agent has been shown to exhibit myorelaxant and sedative activities, apparently due to the blockade of glutamatergic neurotransmission.
A crystalloid solution that contains SODIUM CHLORIDE; SODIUM LACTATE; POTASSIUM CHLORIDE; and CALCIUM CHLORIDE. It is used for FLUID THERAPY.
An isotonic solution; the base contains SODIUM CHLORIDE; POTASSIUM CHLORIDE; and CALCIUM CHLORIDE. Other chemicals, such as SODIUM BICARBONATE or acetate salts may be added, as needed for pH buffering, or as an energy source.
A benzisoxazole derivative with antipsychotic property. Risperidone selectively antagonizes serotonin (5-HT) effects via cortical 5-HT2 receptor, and, to a lesser extent, competes with dopamine at the limbic dopamine D2 receptor. The antagonism leads to decreased psychotic effects, such as hallucinations and delusions. In addition, risperidone has low to moderate affinity for histamine H1, 5-HT1A, 5-HT1C, and 5-HT1D receptors, while it has weak affinity for dopamine D1 and haloperidol-sensitive sigma site receptors.
A sulfonate-based alkylation agent with potential antineoplastic activity. Ritrosulfan appears to alkylate DNA, thereby producing DNA crosslinks, resulting in cell cycle arrest.
A synthetic tetraglycosidic anthracycline antibiotic with antineoplastic activity. Rodorubicin appears to intercalate DNA and causes cell death. Due to its severe cardiotoxic effects, this agent was never marketed.
A phosphodiesterase 4 inhibitor with antidepressant properties.
An anilide used as a long-acting local anesthetic. It has a differential blocking effect on sensory and motor neurons.
A honey bee secretion that is used in the nutrition of larvae and to stimulate development of adult queens. It contains B-complex vitamins such as pantothenic acid (vitamin B5) and vitamin B6 (pyridoxine), amino acids, minerals, enzymes, monosaccharides and 10-hydroxy-2-decenoic acid (10-HDA). Royal jelly has been shown to have antibacterial and immunomodulatory activities.
A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed)
An acetanilide and piperazine derivative that functions as a SODIUM CHANNEL BLOCKER and prevents the release of enzymes during MYOCARDIAL ISCHEMIA. It is used in the treatment of ANGINA PECTORIS.
A sulfur-containing alkyl thionitrite that is one of the NITRIC OXIDE DONORS.
An orally available salicylate and non-steroidal anti-inflammatory drug (NSAID), with anti-inflammatory, analgesic and antipyretic activities. As a prodrug, salsalate is hydrolyzed to salicylic acid which inhibits the expression of cyclooxygenase (COX) enzymes. This prevents the conversion of arachidonic acid into prostaglandin precursors and leads to decreased formation of prostaglandins that are involved in pain, fever and inflammation. In addition, salsalate appears to inhibit nuclear factor-kappa B (NF-kB), thereby preventing activation of the NF-kB-mediated pathway and the expression of genes involved in inflammation.
A highly selective, long-acting beta-2 adrenergic agonist with bronchodilatory activity. Salmeterol's benzene moiety resembles the structure of catecholamines, and occupies the active site of beta-2 adrenergic receptor, while the long, lipophilic side chain of salmeterol, binds to the so called 'exosite' near the beta-2 adrenergic receptors. The binding at the exosite allows the active portion of the molecule to remain at the receptor site and continually engage and disengage with the receptor, therefore providing a long duration of action. This agent stimulates intracellular adenyl cyclase to catalyze the conversion of adenosine triphosphate to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels result in relaxation of bronchiolar smooth muscle, bronchodilation and increased bronchial airflow.
A derivative of isoniazid with antitubercular activity.
A synthetic broad-spectrum fluorinated triazole with potential antifungal activity. Saperconazole preferentially inhibits fungal cytochrome P450 sterol 14 alpha-demethylase (CYP51), an enzyme responsible for the conversion of lanosterol to ergosterol, an important component of the fungal cell membrane. Enzyme inhibition by this agent leads to a decrease in ergosterol pool that distresses synthesis of fungal cell membrane, thereby increases cell membrane permeability, and promotes loss of essential intracellular elements. This ultimately causes fungal cell lysis and death.
A stereoisomer of inositol and a plant sugar alcohol found most abundantly in coconut palm trees, with potential amyloid plaque formation inhibitory activity. Following oral administration, scyllitol crosses the blood brain barrier and inhibits amyloid beta plaque formation in the brain through as of yet unknown mechanism(s). This may lead to reduced disease progression and improvement in cognitive function in patients with Alzheimer disease.
A diarylbutane lignan in which two coniferylalcohols are connected by a beta-beta' bond; a dietary precursor to the mammalian lignan enterodiol.
A selenium compound with the molecular formula H2SO3. It used as a source of SELENIUM, especially for patients that develop selenium deficiency following prolonged PARENTERAL NUTRITION.
An orange-yellow powder that is soluble in carbon disulfide and practically insoluble in both water and organic solvents. Selenium sulfide is used as an ingredient in antidandruff shampoos and as a constituent of fungicides. When heated to decomposition, it emits toxic fumes of sulfur oxides and selenium. The primary routes of potential human exposure to selenium sulfide are dermal contact and inhalation. Contact with selenium sulfide can cause severe redness or irritation of the skin. It is reasonably anticipated to be a human carcinogen. (NCI05)
A naturally occurring organoselenium compound found in many plants, including garlic, onions, and broccoli, with potential antioxidant and chemopreventive activities. Se-Methyl-seleno-L-cysteine (MSC) is an amino acid analogue of cysteine in which a methylselenium moiety replaces the sulphur atom of cysteine. This agent acts as an antioxidant when incorporated into glutathione peroxidase and has been shown to exhibit potent chemopreventive activity in animal models.
A synthetic imidazole derivative, containing a benzothiophene ring, with antifungal, antibacterial, anti-inflammatory and anti-pruritic activity. Besides its ability to inhibit the synthesis of ergosterol, the benzothiophene ring of sertaconazole is able to insert into the fungal cell wall instead of tryptophan. This increases the permeability of the cell wall. In addition, sertaconazole suppresses the release of cytokines.
A selective serotonin uptake inhibitor that is used in the treatment of depression.
A fluorinated isopropyl ether with general anesthetic property. Although the mechanism of action has not been fully elucidated, sevoflurane may act by interfering with the release and re-uptake of neurotransmitters at post-synaptic terminals, and/or alter ionic conductance following receptor activation by a neurotransmitter. Sevoflurane may also interact directly with lipid matrix of neuronal membranes, thereby affecting gating properties of ion channels. In addition, this agent may activate gamma-aminobutyric acid (GABA) receptors hyperpolarizing cell membranes. This results in a general anesthetic effect, a decrease in myocardial contractility and mean arterial pressure as well as an increased respiratory rate.
A synthetic steroidal substance with antineoplastic activity. Atamestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. (NCI04)
A succinate dehydrogenase inhibitor originally isolated from the pathogenic fungus Helminthosposium siccans with antifungal activity. Siccanin, in a quinone-dependent manner, inhibits succinate dehydrogenase in the terminal electron transport chain thereby disrupting cellular respiration.
A continuous protein fiber consisting primarily of FIBROINS. It is synthesized by a variety of INSECTS and ARACHNIDS.
A derivative of clofibrate with antilipidemic activity.
A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.
An alkaloid isolated from the root of Sinomenium acutum with immunomodulatory and potential anti-angiogenic and activities. Although the mechanism of action remains to be fully elucidated, sinomenine appears to inhibit endothelial proliferation mediated through basic fibroblast growth factor (bFGF), which may contribute to its anti-angiogenic effect. In Chinese medicine, this agent has a long track-record in treating arthritis, which is accounted by its ability to inhibit proliferation of synovial fibroblasts and lymphocytes. In addition, sinomenine has been shown to suppress expressions of genes involved in inflammation and apoptosis, such as interleukin-6, a pleiotropic inflammatory cytokine and JAK3 (Janus kinase 3), Daxx (death-associated protein 6), plus HSP27 (heat shock 27kDa protein 1), respectively.
A benzothiazole derivative and dopamine agonist with antioxidant properties that is used in the treatment of PARKINSON DISEASE and RESTLESS LEGS SYNDROME.
A highly soluble, orally available trivalent arsenic-containing telomerase inhibitor with potential antitumor activity. Although the exact mechanism through which sodium metaarsenite exerts its effect has yet to be fully elucidated, this agent appears to target and bind to telomeric sequences, specifically TTAGGG repeats, leading to a shortening of telomeres, and subsequent induction of apoptosis and inhibition of tumor cell growth. In addition, sodium metaarsenite also leads to the translocation of the catalytic subunit of telomerase into the cytoplasm and inhibition of the activity of telomerase. Telomerase is active in most tumors cells and is responsible for the maintenance of telomere length and plays a key role in cellular proliferation, but is quiescent in normal, healthy cells. The susceptibility to sodium metaarsenite seems to be inversely correlated with initial length of telomeres.
A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions.
The disodium salt of carbonic acid with alkalinizing property. When dissolved in water, sodium carbonate forms carbonic acid and sodium hydroxide. As a strong base, sodium hydroxide neutralizes gastric acid thereby acting as an antacid.
A yellowish, crystalline, inorganic compound that emits toxic chromium fumes upon heating. Sodium chromate is highly corrosive and is a strong oxidizing agent. This substance is used in wood preservatives, drilling muds, cutting oils, water treatment, textile dyeing processes, inks, paints, leather tanning and as a corrosion inhibitor. Sodium chromate primarily affects the respiratory tract causing ulcerations, shortness of breath, bronchitis, pneumonia and asthma but can also affect the gastrointestinal tract, liver, kidneys and immune system. This substance is a known human carcinogen and is associated with an increased risk of developing lung cancer and cancer of the sinonasal cavity. (NCI05)
A crystalline powder essential for the metabolism and development of plants and animals as a cofactor for enzymes. (NCI)
An inorganic compound used as a laxative, dietary supplement and for electrolyte-replacement purposes. Phosphate, a predominant intracellular anion, plays an important role in energy storage, osteoblastic and osteoclastic activities, regulating serum calcium concentrations, and numerous cellular phosphate-transfer reactions. Sodium phosphate increases fluidity of the intestinal contents by retention of water by osmotic forces, thereby indirectly inducing intestinal smooth muscle constriction. Sodium phosphate is also used in the renal excretion of hydrogen ions while promoting the reabsorption of sodium ions.
The sodium salt of selenium. As a trace mineral that is toxic in high doses, selenium is a cofactor for glutathione peroxidase, an anti-oxidant enzyme that neutralizes hydrogen peroxide. Selenium may be chemoprotective for certain cancers, particularly prostate cancer. High dietary supplementation with sodium selenate may inhibit the progression of hormone-refractory prostate cancer due, in part, to an antiangiogenesis effect. (NCI04)
A white, inorganic crystalline compound with various industrial uses. Sodium sulfate is found in many common electrolyte solutions used in clinical diagnostic purpose. Since this agent is poorly absorbed in the body, and could draw water out of the cells, sometimes it is used as a cathartic or diuretic.
A white crystal or powder with reducing property. Sodium sulfite exhibits bleaching, de-sulfurizing, and dechlorinating activities. This agent was used by food industry to help maintain the fresh appearance of food products. It is also a component in many drugs, which helps maintain their potency and stability. FDA has ruled sodium sulfite a new animal drug of low regulatory priority.
A water soluble salt and reducing agent that reacts with oxidizing agents. Although its exact mechanism of action is unknown, thiosulfate likely provides an exogenous source of sulfur, thereby hastening the detoxification of cyanide through the enzyme rhodanese (thiosulfate cyanide sulfurtransferase) which converts cyanide to the relatively nontoxic, excretable thiocyanate ion. In addition, this agent neutralizes the reactive alkylating species of nitrogen mustard, thereby decreasing skin toxicity related to nitrogen mustard extravasation. (NCI04)
6-fluorospirochroman-4,4'-imidazolidine-2',5'-dion e; aldose reductase inhibitor which blocks the formation of sorbitol from excess glucose and thus may prevent many diabetic neuropathies.
Proteins which are present in the edible portion of SOYBEANS.
A saturated derivative of sphingosine. As an inhibitor of protein kinase C (PKC), L-threo-dihydrosphingosine competitively binds to the regulatory phorbol-binding domain of PKC, a kinase involved in tumorigenesis. This agent has been shown to act synergistically with other chemotherapeutic agents and may potentiate chemotherapy drug-induced apoptosis in vitro and in vivo. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41910&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41910&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1568"" NCI Thesaurus)
A prodrug and non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Spirapril is converted in the body to its active metabolite spiraprilat. Spiraprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Spiraprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A synthetic organometallic compound containing the element germanium with possible antineoplastic activity. Spirogermanium exhibits significant toxicity, particularly neurotoxicity. (NCI04)
A bifunctional nitrogen alkylating agent with antineoplastic activity and lipophilic properties. Containing a lipophilic hydantoin group that serves as a carrier to cross the blood brain barrier, spiromustine forms covalent linkages with nucleophilic centers in DNA, causing depurination, base-pair miscoding, strand scission, and DNA-DNA cross-linking, which may result in cytotoxicity. (NCI04)
A synthetic derivative of cyclohexane sulfatoplatinum with antineoplastic properties. Spiroplatin induces DNA cross-links, thereby inhibiting DNA replication and RNA and protein synthesis. Similar to other platinum compounds, this agent has been shown to be mutagenic and carcinogenic. (NCI04)
A phosphinic acid-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Fosinoprilat specifically and competitively inhibits angiotensin-converting enzyme thereby decreasing the formation of the potent vasoconstrictor angiotensin II, resulting in diminished vasopressor activity. In addition, angiotensin II-mediated aldosterone secretion by adrenal cortex is decreased, which results in a decrease of sodium retention and an increase in water outflow.
A tyrosine kinase inhibitor that inhibits phospholipase D activity in human neutrophils at a site between the receptor and phospholipase. (NCI)
A preparation of bacterial lysate with potential immunomodulatory activity. Staphage lysate, obtained by phage lysis of Staphylococcal aureus, may be used as an antigenic stimulus to elicit non-specific humoral and cellular immune responses.
A cell permeable alkaloid isolated from Streptomyces staurosporeus exhibiting anti-cancer activity. Staurosporine is a potent, non-selective inhibitor of protein kinases, including protein kinase C. This agent induces apoptosis by an undetermined mechanism. (NCI)
ETHINYL ESTRADIOL and NORGESTREL given in fixed proportions. It has proved to be an effective contraceptive (CONTRACEPTIVES, ORAL, COMBINED).
An intracellular cystatin subtype that is found in a broad variety of cell types. It is a cytosolic enzyme inhibitor that protects the cell against the proteolytic action of lysosomal enzymes such as CATHEPSINS.
A steroid derivative characterized by the hydroxyl group in position C-3 of the steroid skeleton, and a saturated bond in position 5-6 of the B ring.
A water-soluble, colorless crystal with an acid taste that is used as a chemical intermediate, in medicine, the manufacture of lacquers, and to make perfume esters. It is also used in foods as a sequestrant, buffer, and a neutralizing agent. (Hawley's Condensed Chemical Dictionary, 12th ed, p1099; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed, p1851)
organic compound comprising a pyrrole ring with two carbonyl substitutions.
A topical imidazole derivative with broad-spectrum antifungal and antibacterial activity. Sulconazole is excreted in both the feces and urine.
A water-soluble sulfonamide antibiotic used in the treatment of leprosy.
The active metabolite of sulindac, a sulfinylindene derivative with anti-inflammatory, analgesic and antipyretic properties. Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) which inhibits cyclooxygenase (COX-1 and-2)-mediated conversion of arachidonic acid to pro-inflammatory prostaglandins. This agent may possess chemopreventive activity against colorectal tumors through a mechanism that involves the induction of apoptosis. The sulfide metabolite is excreted in the bile and reabsorbed from the intestine, thereby helping to maintain constant blood levels and reduce gastrointestinal side effects. (NCI04)
An inactive metabolite of the nonsteroidal, anti-inflammatory agent sulindac. After oral administration, sulindac undergoes extensive biotransformation including irreversible oxidation to sulindac sulfone. Approximately, one half of an administered dose of sulindac is eliminated through the urine, mostly as the conjugated sulfone metabolite. (NCI04)
A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of MIGRAINE DISORDERS.
A saturated 22-carbon aliphatic alcohol with antiviral activity. Docosanol has a distinct mechanism of action and inhibits fusion between the plasma membrane and the herpes simplex virus envelope, thereby preventing viral entry into cells and subsequent viral activity and replication. Docosanol is used topically in the treatment of recurrent herpes simplex labialis episodes and relieves associated pain and may help heal sores faster.
A flavone with five methoxyl (CH3O) groups at C-5, C-6, C-7, C-8, and C-3'.
A radioconjugate containing hydroxydiphosphonate (HDP) labeled with the metastable radioisotope technetium Tc (99mTc), with radioimaging activity. Upon intravenous administration, skeletal uptake of technetium Tc-99m HDP occurs as a function of skeletal blood flow and osteogenic activity. HDP has a specific affinity for hydroxyapatite crystals in bone where abnormal accumulation of increased osteoid mineralization has occurred. Labeling of HDP with 99mTc allows gamma scintigraphic imaging of areas of abnormal osteogenesis associated with malignant bone lesions.
A synthetic bioactive retinoid with differentiation inducing and potential antineoplastic activities. Like other retinoic acid agents, temarotene binds to and activates retinoic acid receptors (RARs), thereby altering the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.
A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.
A drug used to treat urinary problems caused by an enlarged prostate. It is also used to treat high blood pressure and is being studied in the treatment of other conditions. Terazosin relaxes muscle tissue in blood vessels and in the prostate. It is a type of alpha blocker.
A naphthalene derivative that inhibits fungal SQUALENE EPOXIDASE and is used to treat DERMATOMYCOSES of the skin and nails.
An agent with antilipidemic activity. Animal studies show that terbufibrol is 10 times more active than clofibrate in reducing serum total cholesterol and suggest that it blocks hepatic cholesterol synthesis in a step between acetate and HMG-CoA.
A synthetic triazole derivative structurally related to fluconazole, antifungal Terconazole seems to disrupt cell wall synthesis by inhibiting biosynthesis of ergosterol or other sterols, damaging the fungal cell membrane, altering its permeability, and promoting loss of essential intracellular elements. Terconazole is active against Candida sp.. (NCI04)
A derivative of the phthalanilide compounds. Terephthalamidine belongs to a family of compounds which appear to reversibly bind to the minor groove of the DNA double helix but not intercalate DNA. This agent also has been suggested to form ionic complexes with many biological components in vitro, including nucleic acids, proteins and lipids.
An eight-carbon ester form of Testosterone. The number of ester carbon atoms correlate with the half-life of the prodrug. Testosterone inhibits gonadotropin secretion from the pituitary gland and ablates estrogen production in the ovaries, thereby decreasing endogenous estrogen levels. In addition, this agent promotes the maintenance of male sex characteristics and is indicated for testosterone replacement in hypogonadal males. (NCI04)
A long-acting intramuscular form of the androgen testosterone. Testosterone inhibits gonadotropin secretion from the pituitary gland and ablates estrogen production in the ovaries, thereby decreasing endogenous estrogen levels. In addition, this agent promotes the maintenance of male sex characteristics and is indicated for testosterone replacement in hypogonadal males, delayed puberty, and metastatic mammary cancer. (NCI04)
An four-carbon ester form of Testosterone. The number of ester carbon atoms correlate with the half-life of the prodrug. Testosterone inhibits gonadotropin secretion from the pituitary gland and ablates estrogen production in the ovaries, thereby decreasing endogenous estrogen levels. In addition, this agent promotes the maintenance of male sex characteristics and is indicated for testosterone replacement in hypogonadal males. (NCI04)
The undecanoate ester form of the androgen testosterone, with gonadotropin-secretory inhibiting and hormone replacement activity. As testosterone inhibits the secretion of gonadotropins from the pituitary gland, administration of testosterone decreases the secretion of luteinizing hormone (LH). By inhibiting LH secretion, the growth of Leydig cells, which are normally stimulated by LH to produce testosterone, may be suppressed. In addition, this agent promotes the maintenance of male sex characteristics and can be used for testosterone replacement in hypogonadal males.
A potassium-selective ion channel blocker. (From J Gen Phys 1994;104(1):173-90)
A lactone derivative of LEUCINE that acts as a pancreatic lipase inhibitor to limit the absorption of dietary fat; it is used in the management of obesity.
An imidazole derivative with sympathomimetic activity. Applied locally to the eye or nose, tetrahydrozoline binds to and activates alpha-adrenergic receptors, resulting in vasoconstriction and decreased nasal and ophthalmic congestion.
A natural, bis-benzylisoquinoline alkaloid isolated from the root of the plant Radix stephania tetrandrae. Tetrandrine non-selectively inhibits calcium channel activity and induces G1 blockade of the G1 phase of the cell cycle and apoptosis in various cell types, resulting in immunosuppressive, anti-proliferative and free radical scavenging effects. This agent also increases glucose utilization by enhancing hepatocyte glycogen synthesis, resulting in the lowering of plasma glucose. (NCI04)
A platinum(IV) analogue with antineoplastic activity. Ormaplatin alkylates DNA, forming both inter- and intra-strand platinum-DNA crosslinks, which result in inhibition of DNA replication and transcription and cell-cycle nonspecific cytotoxicity.
A cytotoxic purine antagonist that has both immunosuppressive and antiarthritic activity. (NCI)
A cyclic sulfur amino acid derivative with potential antineoplastic and antioxidant activities. Acting on cellular membranes of malignant cells through an unknown mechanism, timonacic may induce malignant cells to revert back to an untransformed state. This agent may also restore contact inhibition, a phenomenon characterized by the paracrine inhibition of mitosis following the formation of a critical cell mass, presumably the result of cell-to-cell signal transfer. Timonacic may also produce antioxidant effects secondary to its release of cysteine and restoration of glutathione concentrations.
A short-lived, alpha-emitting isotope found in ground water and soils, Radium-224 has been used in biomedical treatments. Radium-224 in drinking water is a potential health risk due to its carcinogenic effects. In the first days after intake, radium heavily concentrates in endosteal bone. Because of the 3.5-day half-life, most Ra-224 decays while on bone surfaces, possibly inducing sarcomas in cells within range of the emitted alpha particles. (NCI04)
A synthetic analogue of thymosin-alpha-1, a 28-amino acid protein derived from the precursor protein prothymosin-alpha. Exhibiting a variety of immunoregulating properties, thymosin-alpha-1 induces differentiation of murine T-cell precursors and human thymocytes and the terminal differentiation of functionally immature cord blood lymphocytes and induces production of IL-2, high affinity IL-2 receptors, and B-cell growth factors by peripheral blood mononuclear cells. T-helper and cytotoxic/suppressor T-cell populations are targets of thymosin activity. Thymosin-alpha-1 has been shown to increase the efficiency of antigen presentation by macrophages and to be an endogenous modulator of alpha-thrombin activity. (NCI04)
A partially purified preparation isolated from the thymus and containing several peptides. Human Thymosin-Fraction 5 (TF-5) possesses immunopotentiating properties and can correct many of the immunological deficiencies resulting from the lack of thymosin function in animal models and in humans. This agent enhances the spontaneous natural killer activity of normal human large granular lymphocytes; exhibits additive effects with recombinant IFN-alpha in enhancing natural killer activity in vitro and; enhances IL2 production, IL2 receptor expression, and IFN-gamma production in mitogen-stimulated large granular lymphocytes. TF-5 may also modulate the secretion of some hypothalamic peptides and pituitary hormones, including prolactin and growth hormone. (NCI04)
A synthetic nucleoside analogue with antineoplastic activity. Tiazofurin (TR) is anabolized intracellularly to an analogue of NAD, tiazole-4-carboxamide adenine dinucleotide (TAD), a potent inhibitor of IMP dehydrogenase (IMPDH); IMPDH is the rate-limiting enzyme for de novo purine synthesis. Inhibition of IMPDH results in reduced levels of guanylates, resulting in the inhibition tumor cell growth in vitro and in vivo. (NCI04)
A synthetic anabolic steroid with estrogenic, androgenic and progestagenic activities. The 3alpha- and 3beta-hydroxy metabolites of tibilone activate estrogenic receptors (ERs) in bone and vaginal tissue leading to a decrease in bone turnover, and decreased vaginal dryness, respectively; derived from the 3beta-hydroxy metabolite, its delta4-isomer activates androgenic receptors (ARs) in the brain and liver and progestogenic receptors (PRs) in endometrial tissue, affecting sexual function, lipid metabolism, and endometrial function, respectively. In breast and endometrial tissue, tibolone metabolites inhibit sulfatase, preventing the conversion of circulating estrone sulfate and estradiol sulfate to estrone and estradiol, respectively; estrogen-mediated effects in the breast and uterus are thus reduced.
A synthetic purpurin with photosensitizing activity. Tin ethyl etiopurpurin preferentially accumulates in tumor cells due to an increased rate of metabolism. Upon exposure to a light source, this agent absorbs light, forming an extended high energy conformational state that produces high quantum yields of singlet oxygen with local cytotoxic effects. (NCI04)
A synthetic imidazole derivative, fungicidal Terconazole inhibits cell wall synthesis by inhibiting the biosynthesis of ergosterol or other sterols, damaging the fungal cell membrane, altering its permeability, and promoting loss of essential intracellular elements. Tioconazole is active against pathogenic Candida. (NCI04)
An alkaline sulfonamide-based diuretic. Tizolemide inhibits sodium reabsorption in the distal convoluted tubules.
A cyclohexyl-containing sulfonylurea compound with antihyperglycemic activity. Glycyclamide, also called tolcyclamide, is less potent than glipizide.
An indazole carboxylic acid derivative with antispermatogenic and potential antineoplastic activity. As a male contraceptive, tolnidamine may irreversibly inhibit sperm production. This agent is less nephrotoxic than ionidamide, but it is just as effective in antispermatogenic action to ionidamide.
A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of EPILEPSY and MIGRAINE DISORDERS, and may also promote weight loss.
A first generation selective estrogen receptor modulator (SERM). Like TAMOXIFEN, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue.
A pyridine and sulfonamide derivative that acts as a sodium-potassium chloride symporter inhibitor (loop diuretic). It is used for the treatment of EDEMA associated with CONGESTIVE HEART FAILURE; CHRONIC RENAL INSUFFICIENCY; and LIVER DISEASES. It is also used for the management of HYPERTENSION.
A non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, trandolapril is converted by de-esterification in the liver into its active form trandolaprilat. Trandolaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Trandolaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
An anabolic steroid used mainly as an anabolic agent in veterinary practice.
The prodrug of a bifunctional sulfonate alkylating agent with myeloablative, immunosuppressive, and antineoplastic activities. Under physiological conditions, treosulfan converts nonenzymatically to L-diepoxybutane via a monoepoxide intermediate. The monoepoxide intermediate and L-diepoxybutane alkylate DNA at guanine residues and produce DNA interstrand crosslinks, resulting in DNA fragmentation and apoptosis. In escalated doses, this agent also exhibits myeloablative and immunosuppressive activities.
The hexacetonide salt form of triamcinolone, a synthetic glucocorticosteroid with immunosuppressive and anti-inflammatory activity. Triamcinolone hexacetonide binds to specific cytosolic glucocorticoid receptors and subsequently interacts with glucocorticoid receptor response element on DNA and alters gene expression. This results in an induction of the synthesis of certain anti-inflammatory proteins while inhibiting the synthesis of certain inflammatory mediators. Consequently, an overall reduction in chronic inflammation and autoimmune reactions are accomplished.
A synthetic dihydrotriazine derivative with antineoplastic properties. As an antifolate agent related to methotrexate (MTX), triazinate inhibits the enzyme dihydrofolate reductase (DHFR), resulting in decreased tetrahydrofolate production and interference with thymidylate synthesis. Unlike MTX, this agent is not converted to polyglutamate forms. Triazinate also inhibits the transport of folates and may be selectively toxic to MTX-resistant tumor cells. (NCI04)
A salicylanilide derivative with antibacterial and antifungal activities banned by FDA due to its photosensitizing effect. Tribromsalan is used as disinfectant in medicated soaps.
Tri-n-butyl phosphate, Bu3-P, TBP. Industrial chemical; used as a plasticizer, in hydraulic fluid, as a solvent and extractant for metal ions, and as a heat exchange agent.
A triglyceride prodrug of butyric acid with potential antineoplastic activity. Butyrate, the active metabolite of tributyrin, inhibits histone deacetylase, resulting in increased differentiation, decreased proliferation, cell cycle arrest, and apoptosis in some tumor cell lines. (NCI04)
The phosphate salt of the synthetic, cell-permeable tricyclic nucleoside triciribine with potential antineoplastic activity. Triciribine inhibits the phosphorylation, activation, and signalling of Akt-1, -2, and -3, which may result in the inhibition of Akt-expressing tumor cell proliferation. Akts are anti-apoptotic serine/threonine-specific protein kinases that phosphorylate and inactivate components of the apoptotic machinery, including Bcl-xL/Bcl-2-associated death promoter (BAD) and caspase 9.
Benzimidazole antiplatyhelmintic agent that is used for the treatment of FASCIOLIASIS and PARAGONIMIASIS.
A triclosan analogue with an antibacterial property. Triclocarban exerts its effect by inhibiting the activity of enoyl-(acyl-carrier protein) (ACP) reductase, widely distributed in bacteria, fungi and plants. ACP reductase catalyses the last step in each cycle of fatty acid elongation in the type II fatty acid synthase systems. As a result, this agent interrupts cell membrane synthesis and leads to bacterial growth inhibition.
A synthetic derivative of androstane with adrenocortical suppressive properties. Trilostane reversibly inhibits 3 beta-hydroxysteroid dehydrogenase delta 5-4 isomerase in the adrenal cortex, resulting in the decreased synthesis of mineralocorticoids and glucocorticoids and the decreased conversion of pregnenolone to progesterone. (NCI04)
A synthetic derivative of trimethylmelamine with antineoplastic properties. An analogue of siderophores (microbial iron chelators), trimelamol induces the formation of a reactive iminium species which may crosslink DNA. (NCI04)
A colchicine analog with potential antineoplastic activity. Trimethylcolchicinic acid binds to tubulin, inhibiting its polymerization into microtubules and preventing cell division. (NCI04)
A lipid soluble methotrexate derivative with potential antineoplastic activity. Trimetrexate glucuronate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylate, with subsequent inhibition of DNA and RNA synthesis. Trimetrexate glucuronate also exhibits antiviral activity. (NCI04)
A nonsteroidal selective estrogen receptor modulator (SERM) with potential antineoplastic activity. Trioxifene competes with estradiol in binding to estrogen receptor alpha (ER alpha), thereby inhibiting ER alpha-mediated signal transduction and gene expression. In addition, trioxifene exerts intrinsic estrogenic activity depending on the tissue. Clinical development of trioxifene has not been preceded due to its side effect profile and lack of increased efficacy over tamoxifen.
the core chemical structure of a number of related anti-estrogen compounds. The triphenylethylene antiestrogens, which include idoxifene, toremifene, chlorotrianisene, raloxifene and tamoxifen, act at the level of the estrogen receptor, triggering inhibition or stimulation of estrogen-dependent gene transcription and cellular physiology. Triphenylethylenes were initially developed for the treatment of estrogen-dependent breast cancers. Selective estrogen receptor modulators (SERMs) such as raloxifene and tamoxifen represent triphenylethylene derivatives that affect transcriptional regulation through modulation of specific alpha and beta estrogen receptors that are differentially expressed in various normal and neoplastic tissues. (NCI04)
A synthetic decapeptide agonist analog of luteinizing hormone releasing hormone (LHRH). Possessing greater potency than endogenous LHRH, triptorelin reversibly represses gonadotropin secretion. After chronic, continuous administration, this agent effects sustained decreases in LH and FSH production and testicular and ovarian steroidogenesis. Serum testosterone concentrations may fall to levels typically observed in surgically castrated men. (NCI04)
An orally bioavailable oxazaphosphorine prodrug with antineoplastic activity. Trofosfamide (TFF) is metabolized predominantly to the cyclophosphamide analogue ifosfamide (IFO), which is then metabolized by liver cytochrome P450s to the active isophosphoramide mustard (IPM). IPM alkylates DNA to form DNA-DNA cross-links, which may result in inhibition of DNA, RNA and protein synthesis, and ultimately lead to tumor cell apoptosis.
A cyclic amine with activity against herpes simplex virus. Tromantadine inhibits absorption of virions to cell surfaces, as well as penetration and uncoating of the virus.
An alkylating agent that bind to the DNA minor groove in a sequence-specific manner and form covalent adducts with adenines, resulting in the inhibition of DNA replication and induction of apoptosis. (NCI04)
A synthetic derivative of staurosporine with antineoplastic activity. 7-hydroxystaurosporine inhibits many phosphokinases, including the serine/threonine kinase AKT, calcium-dependent protein kinase C, and cyclin-dependent kinases. This agent arrests tumor cells in the G1/S of the cell cycle and prevents nucleotide excision repair by inhibiting the G2 checkpoint kinase chk1, resulting in apoptosis. (NCI04)
A quinoxaline derivative and ADRENERGIC ALHPA-2 RECEPTOR AGONIST that is used to manage INTRAOCULAR PRESSURE associated with OPEN-ANGLE GLAUCOMA and OCULAR HYPERTENSION.
The mesylate salt form of doxazosin, a quinazoline compound with smooth muscle relaxing activity. Doxazosin mesylate selectively antagonizes alpha-1-adrenergic receptors in smooth muscle of the bladder neck and prostate, thereby relaxing the smooth muscle and decreasing the obstruction and urethral resistance seen with benign prostate hyperplasia (BPH). This may improve BPH symptoms. This agent also blocks alpha-1-adrenergic receptors in peripheral vascular smooth muscle, which leads to vasodilatation and a subsequent decrease in peripheral vascular resistance.
A multivalent Kunitz-type serine protease inhibitor derived from human urine, with potential protective, anti-fibrinolytic and anticoagulant activities. Upon administration, ulinastatin (or urinary trypsinogen inhibitor) inhibits the activities of a variety of enzymes, including trypsin, chymotrypsin, thrombin, kallikrein, plasmin, elastase, cathepsin, lipase, hyaluronidase, factors IXa, Xa, XIa, and XlIa, and polymorphonuclear leukocyte elastase. In addition, ulinastatin inhibits the excessive release of proinflammatory mediators, such as tumor necrosis factor-alpha, interleukin-6 and -8, and chemokines. Altogether, this agent may improve the microcirculation, perfusion and function of tissues and may protect organ injury.
A glycosyl-phosphatidyl-inositol (GPI) - anchored membrane protein found on the thick ascending limb of the LOOP OF HENLE. The cleaved form of the protein is found abundantly in URINE.
A live, attenuated varicella virus vaccine used for immunization against chickenpox. It is recommended for children between the ages of 12 months and 13 years.
A lipocalin that was orignally characterized from human TEARS. It is expressed primarily in the LACRIMAL GLAND and the VON EBNER GLANDS. Lipocalin 1 may play a role in olfactory transduction by concentrating and delivering odorants to the ODORANT RECEPTORS.
An indole alkaloid that exhibits antimitotic activity by inhibiting microtubule assembly. (NCI)
A vinca alkaloid compound and semi-synthetic vincristine derivative with antineoplastic activity. Vinepidine binds to and stabilizes tubulin, thereby preventing tubulin polymerization and depolymerization, which result in microtubule assembly and disassembly, respectively. Treated cells are unable to complete mitosis process and are arrested in the metaphase, thereby leading to an inhibition of cell growth.
A semisynthetic vinca alkaloid. Vinorelbine binds to tubulin and prevents formation of the mitotic spindle, resulting in the arrest of tumor cell growth in metaphase. This agent may also interfere with amino acid, cyclic AMP. and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis.
An orally active semisynthetic vinca alkaloid with potential antineoplastic activity. Like other vinca alkaloid compounds, vinzolidine binds to and stabilizes tubulin molecules, thereby interfering with microtubule assembly/disassembly dynamics. As a result, vinzolidine prevents mitotic spindle formation and leads to cell cycle arrest in metaphase.
The acetate ester of a fat-soluble vitamin with potent antioxidant properties. Considered essential for the stabilization of biological membranes (especially those with high amounts of polyunsaturated fatty acid), vitamin E is a generic name for a group of compounds known as tocopherols and tocotrienols (tocols). This agent is a potent peroxyl radical scavenger and inhibits noncompetitively cyclooxygenase activity in many tissues, resulting in a decrease in prostaglandin production. Vitamin E also inhibits angiogenesis and tumor dormancy through suppressing vascular endothelial growth factor (VEGF) gene transcription. (NCI04)
a toxic war gas that is inhaled or absorbed through the skin and has harmful effects on the nervous and respiratory system
A potent fungal metabolite isolated from Penicillium wortmannin that selectively inhibits phosphatidylinositol 3-kinase and affects the signal transduction pathway. (NCI)
A synthetic phenethylamine bicyclic derivative with antidepressant activity. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak dopamine reuptake inhibitors. This agent may reduce hormone-related vasomotor symptoms. (NCI04)
A phenoxypropanolamine derivative that is a selective beta-1-adrenergic agonist.
ricin-conjugated monoclonal antibody to T lymphocytes.
Carotenoid having a chemical structure similar to beta-carotene with addition of hydroxyl groups at the number 3 and 3' carbon atoms.
A general purpose reagent is a chemical reagent that has general laboratory application, that is used to collect, prepare, and examine specimens from the human body for diagnostic histopathology, cytology, and hematology, and that is not labeled or otherwise intended for a specific diagnostic application. General purpose reagents include cytological preservatives, decalcifying reagents, fixatives and adhesives, tissue processing reagents, isotonic solutions, and pH buffers.
An ionic salt essential for the synthesis of cholesterol, protein, and fats. Zinc plays an important role in the proper functioning of the immune system. Zinc is required for the enzyme activities necessary for cell division, cell growth, and wound healing as well as the release of vitamin A from the liver. It plays a role in the acuity of the senses of smell and taste and is required to maintain prostate reproductive health and insulin function. Zinc is also involved in the metabolism of carbohydrates. Zinc chloride is administered orally or parenterally as a nutritional supplement.
A coordination complex of the zinc ion and pyrithione, a derivative of the naturally occurring antibiotic aspergillic acid with antimicrobial, antifungal and anti-seborrheic effects. Although the exact mechanism of action remains to be fully elucidated, pyrithione zinc appears to interfere with the membrane transport of ions and metabolites, ultimately leading to a loss of metabolic control. In addition, this agent causes an influx of copper, leading to a reduction in the activity of iron-sulphur proteins resulting in growth inhibition.
A compound given in the treatment of conditions associated with zinc deficiency such as acrodermatitis enteropathica. Externally, zinc sulfate is used as an astringent in lotions and eye drops. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)
A sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, zofenopril is hydrolyzed in vivo into its active form zofenoprilat. Zofenoprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Zofenoprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
An imidazopyridine derivative and short acting GABA-A receptor agonist that is used for the treatment of INSOMNIA.
A benzisoxazole and sulfonamide derivative that acts as a CALCIUM CHANNEL blocker. It is used primarily as an adjunctive antiepileptic agent for the treatment of PARTIAL SEIZURES, with or without secondary generalization.
The racemic form of a nonbenzodiazepine, cyclopyrrolone with hypnotic and sedative activity and without significant anxiolytic activity. Although the exact mechanism of action remains to be fully elucidated, zopiclone is able to bind to and activate the omega-1 subtype of the alpha subunit of the gamma-aminobutyric acid-benzodiazepine GABA receptor complex (GABA-A), a chloride ionophore complex in the central nervous system (CNS). This leads to the opening of chloride channels, causing hyperpolarization, inhibition of neuronal firing, and enhancement of the inhibitory effect of GABA. This eventually leads to a hypnotic effect and allows for an induction of sleep.
A type of automatic, not reentrant, ectopic ventricular rhythm with episodes lasting from a few seconds to a minute which usually occurs in patients with acute myocardial infarction or with DIGITALIS toxicity. The ventricular rate is faster than normal but slower than tachycardia, with an upper limit of 100 -120 beats per minute. Suppressive therapy is rarely necessary.
Renal disease in human immunodeficiency virus (HIV)-infected patients. It is characterized by nephrotic syndrome, azotemia, normal to large kidneys on ultrasound images, and focal segmental glomerulosclerosis on renal biopsy findings.
Albinism affecting the eye in which pigment of the hair and skin is normal or only slightly diluted. The classic type is X-linked (Nettleship-Falls), but an autosomal recessive form also exists. Ocular abnormalities may include reduced pigmentation of the iris, nystagmus, photophobia, strabismus, and decreased visual acuity.
Oculocutaneous albinism is a group of conditions that affect coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have very fair skin and white or light-colored hair. Long-term sun exposure greatly increases the risk of skin damage and skin cancers, including an aggressive form of skin cancer called melanoma, in people with this condition. Oculocutaneous albinism also reduces pigmentation of the colored part of the eye (the iris) and the light-sensitive tissue at the back of the eye (the retina). People with this condition usually have vision problems such as reduced sharpness; rapid, involuntary eye movements (nystagmus); and increased sensitivity to light (photophobia).Researchers have identified multiple types of oculocutaneous albinism, which are distinguished by their specific skin, hair, and eye color changes and by their genetic cause. Oculocutaneous albinism type 1 is characterized by white hair, very pale skin, and light-colored irises. Type 2 is typically less severe than type 1; the skin is usually a creamy white color and hair may be light yellow, blond, or light brown. Type 3 includes a form of albinism called rufous oculocutaneous albinism, which usually affects dark-skinned people. Affected individuals have reddish-brown skin, ginger or red hair, and hazel or brown irises. Type 3 is often associated with milder vision abnormalities than the other forms of oculocutaneous albinism. Type 4 has signs and symptoms similar to those seen with type 2.Several additional types of this disorder have been proposed, each affecting one or a few families.
An acylated inactive complex of streptokinase and human lysine-plasminogen. After injection, the acyl group is slowly hydrolyzed, producing an activator that converts plasminogen to plasmin, thereby initiating fibrinolysis. Its half-life is about 90 minutes compared to 5 minutes for TPA; (TISSUE PLASMINOGEN ACTIVATOR); 16 minutes for UROKINASE-TYPE PLASMINOGEN ACTIVATOR and 23 minutes for STREPTOKINASE. If treatment is initiated within 3 hours of onset of symptoms for acute myocardial infarction, the drug preserves myocardial tissue and left ventricular function and increases coronary artery patency. Bleeding complications are similar to other thrombolytic agents.
An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid.
Loss of blood during a surgical procedure.
A congenital defect in the neck that occurs during early embryonic development. It is caused by developmental abnormalities of the pharyngeal arches and results in the development of a cyst or a fissure in the side of the neck.
Agents causing the narrowing of the lumen of a bronchus or bronchiole.
A second-generation platinum compound with a broad spectrum of antineoplastic properties. Carboplatin contains a platinum atom complexed with two ammonia groups and a cyclobutane-dicarboxyl residue. This agent is activated intracellularly to form reactive platinum complexes that bind to nucleophilic groups such as GC-rich sites in DNA, thereby inducing intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links. These carboplatin-induced DNA and protein effects result in apoptosis and cell growth inhibition. This agent possesses tumoricidal activity similar to that of its parent compound, cisplatin, but is more stable and less toxic. (NCI04)
Epidermolytic hyperkeratosis (EHK), also termed bullous congenital ichthyosiform erythroderma (BCIE), is a keratinization disorder with an incidence of approximately 1 in 200,000 in the USA. The clinical phenotype of EHK is characterized by erythema and widespread formation of epidermal blisters developing at birth. Later in life, bullous erythema is replaced by progressive hyperkeratosis, involving thickening of the cornified layer of the epidermis (summary by Muller et al., 2006). Goldsmith (1976) used the designation of epidermolytic hyperkeratosis for the condition that is called bullous congenital ichthyosiform erythroderma (BCIE) when generalized, and ichthyosis hystrix (see 146600) when localized. They are presumably distinct entities. A form of epidermolytic hyperkeratosis that is limited to the palms and soles, designated palmoplantar keratoderma (EPPK; 144200), is caused by mutation in the keratin gene KRT9 (607606), and a mild form of EPPK can also be caused by mutation in KRT1.
A chronic, congenital ichthyosis inherited as an autosomal recessive trait. Infants are usually born encased in a collodion membrane which sheds within a few weeks. Scaling is generalized and marked with grayish-brown quadrilateral scales, adherent at their centers and free at the edges. In some cases, scales are so thick that they resemble armored plate.
A term referring to disorders affecting the muscles of the head and neck, particularly the masticatory muscles.
A childhood counterpart of abdominal or extra-abdominal desmoid tumors, characterized by firm subcutaneous nodules that grow rapidly in any part of the body but do not metastasize. The adult form of abdominal fibromatosis is FIBROMATOSIS, ABDOMINAL. (Stedman, 25th ed)
Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4-POSITIVE T-LYMPHOCYTES. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications.
A long chain polymer of sulfated glucose with strong hydrophilic properties that binds to various membranes. Dextran sulfate has been shown to inhibit the binding of HIV-1 to CD4+ T lymphocytes by specific binding of virion-associated gp120.
An abnormal communication between any part of the digestive system and another organ or cavity.
10,11-dihydro-5-methyldibenzocyclohepten -5,10-imine; PCP analog, anticonvulsant, and excitatory aminoacid antagonist that acts on the calcium channel site of NMDA receptors; USP lists as a neuroprotectant.
A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.
A delta-selective opioid (ANALGESICS, OPIOID). It can cause transient depression of mean arterial blood pressure and heart rate.
A chronic autoimmune inflammatory disorder characterized by the formation of subepidermal blisters in the skin and the mucous membranes.
Dystrophic epidermolysis bullosa (DEB) is a genetic skin disorder affecting skin and nails that usually presents at birth. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Each type is further divided into multiple clinical subtypes. Absence of a known family history of DEB does not preclude the diagnosis. Clinical findings in severe generalized RDEB include skin fragility manifest by blistering with minimal trauma that heals with milia and scarring. Blistering and erosions affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, malnutrition and vitamin and mineral deficiency may lead to growth restriction in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into ""mitten"" hands and feet, with contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the mutilating scarring seen in severe generalized RDEB. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB.
Epidermolysis bullosa simplex (EBS) is characterized by fragility of the skin (and mucosal epithelia in some cases) that results in non-scarring blisters and erosions caused by minor mechanical trauma. The current classification of epidermolysis bullosa (EB) includes two major types and 17 minor subtypes of EBS; all share the common feature of blistering above the dermal-epidermal junction at the ultrastructural level. The four most common subtypes of EBS are the focus of this GeneReview: EBS, localized (EBS-loc; previously known as Weber-Cockayne type). EBS, generalized intermediate (EBS-gen intermed; previously known as Koebner type). EBS-with mottled pigmentation (EBS-MP). EBS, generalized severe (EBS-gen sev; previously known as Dowling-Meara type). The phenotypes for these subtypes range from relatively mild blistering of the hands and feet to more generalized blistering, which can be fatal. In EBS-loc, blisters are rarely present or minimal at birth and may occur on the knees and shins with crawling or on the feet at approximately age 18 months; some individuals manifest the disease in adolescence or early adulthood. Blisters are usually confined to the hands and feet, but can occur anywhere if trauma is significant. In EBS, gen intermed, blisters may be present at birth or develop within the first few months of life. Involvement is more widespread than in EBS-loc, but generally milder than in EBS-gen sev. In EBS-MP, skin fragility is evident at birth and clinically indistinguishable from EBS-gen sev; over time, progressive brown pigmentation interspersed with hypopigmented spots develops on the trunk and extremities, with the pigmentation disappearing in adult life. Focal palmar and plantar hyperkeratoses may occur. In EBS-gen sev, onset is usually at birth; severity varies greatly, both among and within families. Widespread and severe blistering and/or multiple grouped clumps of small blisters are typical and hemorrhagic blisters are common. Improvement occurs during mid- to late childhood. Progressive hyperkeratosis of the palms and soles begins in childhood and may be the major complaint of affected individuals in adult life. Nail dystrophy and milia are common. Both hyper- and hypopigmentation can occur. Mucosal involvement in EBS-gen sev may interfere with feeding, especially in neonates and infants. Blistering can be severe enough to result in neonatal or infant death.
Junctional epidermolysis bullosa (JEB) is characterized by fragility of the skin and mucous membranes, manifest by blistering with little or no trauma. Blistering may be severe and granulation tissue can form on the skin around the oral and nasal cavities, fingers and toes, and internally around the upper airway. Blisters generally heal with no significant scarring. Broad classification of JEB includes JEB generalized severe and JEB generalized intermediate. In JEB generalized severe, blisters are present at birth or become apparent in the neonatal period. Congenital malformations of the urinary tract and bladder may also occur. In JEB generalized intermediate, the phenotype may be mild with blistering localized to hands, feet, knees, and elbows with or without renal or ureteral involvement. Some individuals never blister after the newborn period. Additional features shared by JEB and the other major forms of epidermolysis bullosa (EB) include congenital localized absence of skin (aplasia cutis congenita), milia, nail dystrophy, scarring alopecia, hypotrichosis, pseudosyndactyly, and other contractures.
A kappa opioid receptor agonist. The compound has analgesic action and shows positive inotropic effects on the electrically stimulated left atrium. It also affects various types of behavior in mammals such as locomotion, rearing, and grooming.
Acquired defect of cellular immunity that occurs in cats infected with feline immunodeficiency virus (FIV) and in some cats infected with feline leukemia virus (FeLV).
A congenital form of torticollis resulting from shortening of the sternocleidomastoid muscle and leading to a limited range of motion in both rotation and lateral bending.
A mutation occurring within the protein-coding region of a gene which results in a shift in the reading frame of the encoded protein. Frameshift mutations often result in the premature truncation of a gene product.
A centrally acting adrenergic agonist with non-stimulant and antihypertensive property. Guanfacine selectively stimulates alpha-2 adrenergic receptors in the central nervous system, thereby resulting in inhibition of sympathetic nervous system outflow. Used alone or in combination with other drugs, this agent causes reduction of peripheral and renal vascular resistance, and lowers both systolic and diastolic blood pressure and heart rate.
Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.
Downward displacement of any one of the HEART VALVES from its normal position. This usually results in failed valve closure.
Infections with organisms of the genus HELICOBACTER, particularly, in humans, HELICOBACTER PYLORI. The clinical manifestations are focused in the stomach, usually the gastric mucosa and antrum, and the upper duodenum. This infection plays a major role in the pathogenesis of type B gastritis and peptic ulcer disease.
Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1.
Holoprosencephaly (HPE) is a structural anomaly of the brain in which there is failed or incomplete separation of the forebrain early in gestation. Classic HPE encompasses a continuum of brain malformations including (in order of decreasing severity): alobar, semilobar, lobar, and middle interhemispheric variant (MIHV) type HPE; a septopreoptic type has also been described. Other CNS abnormalities not specific to HPE may also occur. HPE is accompanied by a spectrum of characteristic craniofacial anomalies in approximately 80% of individuals with HPE. Developmental delay is present in virtually all individuals with the HPE spectrum of CNS anomalies. Seizures and pituitary dysfunction are common. Most affected fetuses do not survive; severely affected children typically do not survive beyond early infancy, while a significant proportion of more mildly affected children survive past 12 months. Mildly manifesting individuals without appreciable brain anomalies on conventional neuroimaging may be described as having ""microform"" HPE.
An ichthyosiform abnormality of the skin with congenital onset.
Most common form of ICHTHYOSIS characterized by prominent scaling especially on the exterior surfaces of the extremities. It is inherited as an autosomal dominant trait.
X-linked ichthyosis is clinically characterized by widespread, dark brown, polygonal scales and generalized dryness. Cutaneous manifestations are present soon after birth and usually do not improve with age. The histopathology of XLI typically shows compact hyperkeratosis and slight acanthosis with a normal granular layer (summary by Takeichi and Akiyama, 2016). X-linked ichthyosis is fundamentally the same disorder as placental steroid sulfatase deficiency, which is often first noted in the pregnant mother of affected males by decreased estrogen or delayed progression of parturition (Alperin and Shapiro, 1997). This is thus an example of affinity ('lumping') of phenotypes thought previously to be separate, the opposite of genetic heterogeneity. Schnyder (1970) gave a useful classification of the inherited ichthyoses. Hernandez-Martin et al. (1999) provided a comprehensive review of X-linked ichthyosis. They pointed out that among all genetic disorders X-linked ichthyosis shows one of the highest ratios of chromosomal deletions; complete deletion has been found in up to 90% of patients. Takeichi and Akiyama (2016) reviewed inherited nonsyndromic forms of ichthyosis.
The citrate salt of an antineoplastic nonsteroidal selective estrogen receptor modulator (SERM). Tamoxifen competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA. The result is a reduction in DNA synthesis and cellular response to estrogen. In addition, tamoxifen up-regulates the production of transforming growth factor B (TGFb), a factor that inhibits tumor cell growth, and down-regulates insulin-like growth factor 1 (IGF-1), a factor that stimulates breast cancer cell growth. Tamoxifen also down-regulates protein kinase C (PKC) expression in a dose-dependant manner, inhibiting signal transduction and producing an antiproliferative effect in tumors such as malignant glioma and other cancers that overexpress PKC.
A prostacyclin analogue with potential chemopreventive activity. Iloprost binds to the prostacyclin receptor in various target cells, thereby causing vasodilation, inhibition of platelet aggregation, and decreased tumor cell adhesion to endothelium among other effects. Prostacyclin is a naturally occurring eicosanoid with anti-inflammatory, antineoplastic, and anti-metastatic properties. (NCI05)
Waardenburg syndrome type 3 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; presence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi; and upper limb abnormalities (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 3 is also referred to as 'Klein-Waardenburg syndrome' (Gorlin et al., 1976). Clinical Variability of Waardenburg Syndrome Types 1-4 Waardenburg syndrome has been classified into 4 main phenotypes. Type I Waardenburg syndrome (WS1; 193500) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type II (WS2) is distinguished from type I by the absence of dystopia canthorum. WS type III has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type IV (WS4; 277580), also known as Waardenburg-Shah syndrome, has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010).
Virus diseases caused by the Lentivirus genus. They are multi-organ diseases characterized by long incubation periods and persistent infection.
The sodium salt of levothyroxine, a synthetic levoisomer of thyroxine (T4) that is similar to the endogenous hormone produced by the thyroid gland. In peripheral tissues, levothyroxine is deiodinated by 5'-deiodinase to form triiodothyronine (T3). T3 enters the cell and binds to nuclear thyroid hormone receptors; the activated hormone-receptor complex in turn triggers gene expression and produces proteins required in the regulation of cellular respiration; thermogenesis; cellular growth and differentiation; and the metabolism of proteins, carbohydrates and lipids. T3 also exhibits cardiostimulatory effects.
A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.
A type of lymphoma that grows and spreads quickly and has severe symptoms. Also called aggressive lymphoma and intermediate-grade lymphoma.
An antiquated term that refers to a non-Hodgkin lymphoma with intermediate grade histologic features.
A non-Hodgkin lymphoma characterized by a diffuse proliferation of predominantly large neoplastic B lymphocytes. It is the most frequently seen type of non-Hodgkin lymphoma, representing 30%-40% of the cases. Morphologic variants include centroblastic lymphoma, immunoblastic lymphoma, and anaplastic lymphoma. Subtypes/entities include T-cell/histiocyte rich large B-cell lymphoma, primary diffuse large B-cell lymphoma of the central nervous system, plasmablastic lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, and ALK-positive large B-cell lymphoma.
A follicular lymphoma which contains more than 15 centroblasts per 40X high-power microscopic field.
A diffuse large B-cell lymphoma characterized by the presence of immunoblasts with uniformly round-to-oval nuclei, a prominent nucleolus, and abundant cytoplasm.
An antiquated term that refers to a non-Hodgkin lymphoma with low grade histologic features.
A lymphoma composed of immature small to medium-sized precursor lymphoid cells (lymphoblasts). It includes the B- and T-cell lymphoblastic lymphoma.
An antiquated term referring to non-Hodgkin lymphomas with a mixed cellular composition. This term applies to both B- and T- cell non-Hodgkin lymphomas.
A follicular lymphoma which contains 6-15 centroblasts per 40X high-power microscopic field.
A low-grade malignant lymphoma of predominantly follicular pattern. Follicles are of relatively uniform size and shape and the cells are usually somewhat larger than normal lymphocytes. Nuclei are irregular with prominent indentations and cytoplasm can rarely be identified. Cells exhibiting these characteristics are often called centrocytes.
A group of heterogeneous lymphoid tumors representing malignant transformations of T-lymphocytes.
A T-cell non-Hodgkin lymphoma arising from the skin. Representative examples include mycosis fungoides and primary cutaneous anaplastic large cell lymphoma.
A group of malignant lymphomas thought to derive from peripheral T-lymphocytes in lymph nodes and other nonlymphoid sites. They include a broad spectrum of lymphocyte morphology, but in all instances express T-cell markers admixed with epithelioid histiocytes, plasma cells, and eosinophils. Although markedly similar to large-cell immunoblastic lymphoma (LYMPHOMA, LARGE-CELL, IMMUNOBLASTIC), this group's unique features warrant separate treatment.
A quaternary ammonium parasympathomimetic agent with the muscarinic actions of ACETYLCHOLINE. It is hydrolyzed by ACETYLCHOLINESTERASE at a considerably slower rate than ACETYLCHOLINE and is more resistant to hydrolysis by nonspecific CHOLINESTERASES so that its actions are more prolonged. It is used as a parasympathomimetic bronchoconstrictor agent and as a diagnostic aid for bronchial asthma. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1116)
Allergic reaction to milk (usually cow's milk) or milk products. MILK HYPERSENSITIVITY should be differentiated from LACTOSE INTOLERANCE, an intolerance to milk as a result of congenital deficiency of lactase.
An antiarrhythmia agent used primarily for ventricular rhythm disturbances.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).
A condition of abnormally low AMNIOTIC FLUID volume. Principal causes include malformations of fetal URINARY TRACT; FETAL GROWTH RETARDATION; GESTATIONAL HYPERTENSION; nicotine poisoning; and PROLONGED PREGNANCY.
An abnormal passage within the mouth communicating between two or more anatomical structures.
Piebaldism is a rare autosomal dominant trait characterized by the congenital absence of melanocytes in affected areas of the skin and hair. A white forelock of hair, often triangular in shape, may be the only manifestation, or both the hair and the underlying forehead may be involved. The eyebrows and eyelashes may be affected. Irregularly shaped white patches may be observed on the face, trunk, and extremities, usually in a symmetrical distribution. Typically, islands of hyperpigmentation are present within and at the border of depigmented areas (summary by Thomas et al., 2004).
A collection of fluid in the pleural cavity as a result of malignant disease. Malignant pleural effusion fluid often contains free-floating malignant cells. --2004
A syndrome characterized by new neuromuscular symptoms that occur at least 15 years after clinical stability has been attained in patients with a prior history of symptomatic poliomyelitis. Clinical features include new muscular weakness and atrophy of the limbs, bulbar innervated musculature, and muscles of respiration, combined with excessive fatigue, joint pain, and reduced stamina. The process is marked by slow progression and periods of stabilization. (From Ann NY Acad Sci 1995 May 25;753:68-80)
The quality of being secluded from the presence or view of others; the condition of being concealed or hidden; the ability of a person to control the availability of information about and exposure of him- or herself.
Suspensions of attenuated or killed protozoa administered for the prevention or treatment of infectious protozoan disease.
An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis.
A receptor for MACROPHAGE COLONY-STIMULATING FACTOR encoded by the c-fms proto-oncogene (GENES, FMS). It contains an intrinsic protein-tyrosine kinase activity. When activated the receptor undergoes autophosphorylation, phosphorylation of down-stream signaling molecules and rapid down-regulation.
An abnormal passage communicating between any component of the respiratory tract or between any part of the respiratory system and surrounding organs.
8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-3- benzazepin-7-ol; D2 dopamine antagonist and tranquilizer.
Acquired defect of cellular immunity that occurs naturally in macaques infected with SRV serotypes, experimentally in monkeys inoculated with SRV or MASON-PFIZER MONKEY VIRUS; (MPMV), or in monkeys infected with SIMIAN IMMUNODEFICIENCY VIRUS.
skin diseases characterized by local or general distributions of blisters.
A common congenital midline defect of fusion of the vertebral arch without protrusion of the spinal cord or meninges. The lesion is also covered by skin. L5 and S1 are the most common vertebrae involved. The condition may be associated with an overlying area of hyperpigmented skin, a dermal sinus, or an abnormal patch of hair. The majority of individuals with this malformation are asymptomatic although there is an increased incidence of tethered cord syndrome and lumbar SPONDYLOSIS. (From Joynt, Clinical Neurology, 1992, Ch55, p34)
Spina bifida is a condition in which the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. As a result, when the spine forms, the bones of the spinal column do not close completely around the developing nerves of the spinal cord. Part of the spinal cord may stick out through an opening in the spine, leading to permanent nerve damage. Because spina bifida is caused by abnormalities of the neural tube, it is classified as a neural tube defect.Children born with spina bifida often have a fluid-filled sac on their back that is covered by skin, called a meningocele. If the sac contains part of the spinal cord and its protective covering, it is known as a myelomeningocele. The signs and symptoms of these abnormalities range from mild to severe, depending on where the opening in the spinal column is located and how much of the spinal cord is affected. Related problems can include a loss of feeling below the level of the opening, weakness or paralysis of the feet or legs, and problems with bladder and bowel control. Some affected individuals have additional complications, including a buildup of excess fluid around the brain (hydrocephalus) and learning problems. With surgery and other forms of treatment, many people with spina bifida live into adulthood.In a milder form of the condition, called spina bifida occulta, the bones of the spinal column are abnormally formed, but the nerves of the spinal cord usually develop normally. Unlike in the more severe form of spina bifida, the nerves do not stick out through an opening in the spine. Spina bifida occulta most often causes no health problems, although rarely it can cause back pain or changes in bladder function.
A disorder characterized by an arrhythmia with an above normal rate.
A radiopharmaceutical core of chelating agent DTPA (diethylenetriaminepentaacetic acid) complexed with the gamma-emitting radionuclide technetium Tc 99m with radioimaging application. Tc-99m-DTPA has been utilized as a radiotracer, when conjugated to tissue specific molecules, in a wide variety of nuclear imaging studies, including brain, lung, and renal function studies.
A progressive neurological disorder characterized by the limitation of movement of the spinal cord within the spine. It is caused by the presence of congenital or acquired tissue attachments in the spinal cord. Signs and symptoms include low back pain, scoliosis, weakness in the legs, and incontinence.
A synthetic pentapeptide which is the active site of the naturally occurring hormone thymopoietin with immunomodulating properties. Thymopentin enhances the production of thymic T cells and may help restore immunocompetence in immunosuppressed subjects. This agent also augments the effects of ionizing radiation by arresting cancer cells in the G2/M phase of the cell cycle. (NCI04)
Accumulation of urine within the bladder because of the inability to urinate.
An abnormal passage between two or more BLOOD VESSELS, between ARTERIES; VEINS; or between an artery and a vein.
Volume of blood remaining in a ventricle at the end of SYSTOLE.
Demyelinating leukoencephalomyelitis of sheep caused by the VISNA-MAEDI VIRUS. It is similar to but not the same as SCRAPIE.
A nonselective beta-adrenoceptor antagonist used in the treatment of glaucoma.
fatty acid with anticonvulsant properties.
A deoxyuridine prodrug with potential antineoplastic activity. Upon cellular uptake, 2'-F-ara-deoxyuridine (FAU) is phosphorylated by thymidine kinase to FAU monophosphate and subsequently methylated in the 5'-position by thymidylate synthase (TS) to its activated form, 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl) 5-methyluracil monophosphate (FMAUMP). FMAUMP is incorporated into DNA leading to an inhibition of DNA synthesis and so cell growth. The catalytic activity of TS is critical to activation of FAU and subsequent incorporation into DNA. FAU may be beneficial in the case of tumors with high TS activity that are resistant to TS inhibitors.
A synthetic small molecule with radiosensitizing activity. Efaproxiral increases oxygen levels in hypoxic tumor tissues by binding non-covalently to the hemoglobin tetramer and decreasing hemoglobin-oxygen binding affinity. Increasing tumor oxygenation reduces tumor radioresistance. (NCI04)
A synthetic derivative of hydroxyurea with antiasthmatic properties. The leukotriene inhibitor zileuton blocks 5-lipoxygenase, which catalyzes the formation of leukotrienes from arachidonic acid; causes bronchodilation; decreases bronchial mucous secretion and edema; and may prevent or decrease the symptoms of asthma. (NCI04)
An ester of sulfisoxazole, a broad-spectrum sulfanilamide and a synthetic analog of para-aminobenzoic acid (PABA) with antibacterial property. Sulfisoxazole acetyl competes with PABA for the bacterial enzyme dihydropteroate synthase, thereby preventing the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. This leads to an inhibition of bacterial folic acid synthesis and de novo synthesis of purines and pyrimidines, ultimately resulting in cell growth arrest and cell death.
An amphiphilic compound that exhibits a direct phototoxic effect, thereby inducing tumor necrosis. (NCI)
2-pyridinylmethylsulfinylbenzimidazole proton pump inhibitor that is used in the treatment of GASTROESOPHAGEAL REFLUX and PEPTIC ULCER.
A synthetic derivative of emetine; used in the treatment of intestinal amoebiasis.
A pentapeptide originally isolated from the marine mollusk Dolabella auricularia with potential antineoplastic activity. Binding to tubulin, Dolastatin 10 inhibits microtubule assembly, resulting in the formation of tubulin aggregates and inhibition of mitosis. This agent also induces tumor cell apoptosis through a mechanism involving bcl-2, an oncoprotein that is overexpressed in some cancers. (NCI04)
An agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic activity. Englitazone also appears to decrease triacylglycerol levels in animal studies.
An enediyne antineoplastic antibiotic hybrid containing an anthranilate moiety. Esperamicin A1 is isolated from the bacterium Actinomadura verrucosospora. The anthranilate component of esperamicin A1 intercalates DNA and the benzene diradical intermediate of the enediyne core binds to the minor groove of DNA, resulting in single- and double-stranded breaks in DNA and apoptosis. (NCI04)
A STEROID with GLUCOCORTICOID RECEPTOR activity that is used to manage the symptoms of ASTHMA; ALLERGIC RHINITIS, and ATOPIC DERMATITIS.
A synthetic lipid-lowering agent with antilipidemic and potential antineoplastic properties. Fluvastatin competitively inhibits hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent lowers plasma cholesterol and lipoprotein levels, and modulates immune responses through the suppression of MHC II (major histocompatibility complex II) on interferon gamma-stimulated antigen-presenting cells such as human vascular endothelial cells. Due to its anti-inflammatory effects mediated by alterations of lipid metabolism, fluvastatin may possess chemopreventive and therapeutic antineoplastic properties.
A synthetic corticosteroid with anti-inflammatory, antipruritic, and vasoconstrictor activities. Halobetasol, a topical steroid, diffuses across cell membranes to interact with cytoplasmic corticosteroid receptors located in both the dermal and intradermal cells, thereby activating gene expression of anti-inflammatory proteins mediated via the corticosteroid receptor response element. Specifically, this agent induces phospholipase A2 inhibitory proteins, which inhibit the release of arachidonic acid, thereby inhibiting the biosynthesis of potent mediators of inflammation, such as prostaglandins and leukotrienes. As a result, halobetasol reduces edema, erythema, and pruritus through its cutaneous effects on vascular dilation and permeability.
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*38 allele family.
Class I human histocompatibility (HLA) surface antigens encoded by alleles on locus B of the HLA complex. The HLA-G antigens are considered non-classical class I antigens due to their distinct tissue distribution which differs from HLA-A; HLA-B; and HLA-C antigens. Note that several isoforms of HLA-G antigens result from alternative splicing of messenger RNAs produced from the HLA-G*01 allele.
A lymphohematopoietic cytokine that plays a role in regulating the proliferation of ERYTHROID PRECURSOR CELLS. It induces maturation of MEGAKARYOCYTES which results in increased production of BLOOD PLATELETS. Interleukin-11 was also initially described as an inhibitor of ADIPOGENESIS of cultured preadipocytes.
An orally bioavailable east Asian herbal supplement, with potential gastro- and neuro-protective, immunostimulatory, anti-inflammatory, anti-cancer, anti-cachexic and antioxidant activities. Sipjeondaebo-tang is comprised of various components, including Angelica root (Angelicae Gigantis Radix), the rhizome of Cnidium officinale Makino (Cnidii Rhizoma), Radix Paeoniae, Rehmannia glutinosa root (Rehmanniae Radix Preparata), Ginseng root (Ginseng Radix Alba), Atractylodes lancea root (Atractylodis Rhizoma Alba), the dried sclerotia of Poria cocos (Poria cocos Sclerotium), Licorice root (Glycyrrhizae Radix), Astragalus root (Astragali Radix), and the dried bark of Cinnamomum verum (Cinnamomi Cortex). Upon administration, and although the exact mechanism of action has yet to be fully elucidated, sipjeondaebo-tang may exert its effect through the various mechanism of actions that may be attributed to the different herbs.
An enzyme which catalyzes the hydrolysis of LACTOSE to D-GALACTOSE and D-GLUCOSE. Defects in the enzyme cause LACTOSE INTOLERANCE.
A synthetic nonapeptide analogue of the natural gonadotrophin releasing hormone (GnRH) with potential antineoplastic activity. Deslorelin binds to and activates pituitary gonadotropin releasing hormone (GnRH) receptors. Continuous, prolonged administration of goserelin in males results in pituitary GnRH receptor desensitization and inhibition of pituitary secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to a significant decline in testosterone production; in females, prolonged administration results in a decrease in estradiol production. (NCI04)
A benzothiazine and thiazole derivative that acts as a NSAID and cyclooxygenase-2 (COX-2) inhibitor. It is used in the treatment of RHEUMATOID ARTHRITIS; OSTEOARTHRITIS; and ANKYLOSING SPONDYLITIS.
A cell-permeable analog of erbstatin, a compound isolated from Streptomyces that inhibits the autophosphorylation of epidermal growth factor receptor. Erbstatin analogue competitively inhibits epidermal growth factor receptor-associated tyrosine kinase, inhibiting the activation of v-abl tyrosine kinase. In addition, this agent has induced apoptosis in mouse thymocytes and inhibits the G2/M phase of the cell cycle. (NCI)
A guanine analogue with antineoplastic activity. O6-benzylguanine binds the DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase (AGT), transferring the benzyl moiety to the active-site cysteine and resulting in inhibition of AGT-mediated DNA repair. Co-administration of this agent potentiates the effects of other chemotherapeutic agents that damage DNA. (NCI04)
A synthetic polypeptide based on the arg-gly-asp (RGD) sequence present in some cell adhesion molecules. Displays antimetastatic activity in model systems.
Prohibitin (272 aa, ~30 kDa) is encoded by the human PHB gene. This protein may be involved in both aging and the regulation of DNA synthesis.
A water-soluble para-aminophenol derivative and ester prodrug of acetaminophen in which acetaminophen is bound to the carboxylic acid diethylglycine, with analgesic and antipyretic activities. Upon intravenous administration, propacetamol is hydrolyzed by plasma esterases into its active form acetaminophen. Although the exact mechanism of action has yet to be fully elucidated despite its widespread use, acetaminophen enters the central nervous system and acts centrally. This agent binds to cyclooxygenase (COX) and prevents the metabolism of arachidonic acid to prostaglandin. A reduction in prostaglandin formation relieves pain and reduces fever. Acetaminophen may also act centrally on cannabinoid receptors and on N-methyl-D-aspartate (NMDA) receptors.
A synthetic cytidine analogue and a cytidine deaminase inhibitor with anticancer activity. Following metabolic activation by phosphorylation and incorporation into DNA, zebularine inhibits DNA methyltransferase through covalent complex formation between the enzyme and zebularine-substituted DNA, hence resulting in non-specific, genome-wide induction of demethylation including the removal of aberrant methylation of promoter regions of genes critical for normal cellular functions.
An ellipticine derivative and topoisomerase II inhibitor with antineoplastic activity. Retelliptine intercalates with DNA and inhibits topoisomerase II during DNA replication. In addition, this agent appears to induce cell cycle arrest at G2/M phase and apoptosis mediated through the Fas/Fas ligand death receptor and the mitochondrial pathway.
A hydroxypyridone antimycotic agent with broad-spectrum activity against dermatophytes, yeasts, and molds.
A methanesulfonate salt form, a staurosporine analog that inhibits protein kinase C and induces apoptosis. (NCI)
An allyl-S compound with the structure C=CCSCC(N)C(O)O.
An epoxide-containing cyclotetrapeptide with antitumor activity. It is an irreversible inhibitor of histone deacetylase.
A non-thiol angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, zabicipril is rapidly converted in vivo by de-esterification into its active form zabiciprilat. Zabiciprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Zabiciprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
Adherent debris produced when cutting the enamel or dentin in cavity preparation. It is about 1 micron thick and its composition reflects the underlying dentin, although different quantities and qualities of smear layer can be produced by the various instrumentation techniques. Its function is presumed to be protective, as it lowers dentin permeability. However, it masks the underlying dentin and interferes with attempts to bond dental material to the dentin.
A bacterial infection related to a device used to replace a missing body part. The infection may occur during the operation from direct contamination or post-operatively through hematogenous spread.
A localized or generalized inflammatory skin disorder characterized by the formation of papules and ring-shaped plaques in the skin. Morphologically these lesions are granulomatous inflammatory processes with central necrosis surrounded by palisading histiocytes.
A rare syndrome characterized by fever, skin papules and plaques, and leukocytosis. Morphologically, the skin lesions show neutrophilic infiltrates and dermal edema. It may occur in the absence of underlying conditions. It may also be associated with the presence of cancer or may be a side effect of medications.
A group of autosomal recessive or X-linked inherited metabolic disorders caused by defects in the function of the lysosomes. Signs and symptoms include hepatomegaly, splenomegaly, nervous system manifestations, skeletal abnormalities, and mental deterioration. Representative examples include Gaucher disease, Niemann-Pick disease, Wolman disease, and Fabry disease.
A laboratory test result indicating the presence of fungi or yeasts in the blood.
A complication of OVULATION INDUCTION in infertility treatment. It is graded by the severity of symptoms which include OVARY enlargement, multiple OVARIAN FOLLICLES; OVARIAN CYSTS; ASCITES; and generalized EDEMA. The full-blown syndrome may lead to RENAL FAILURE, respiratory distress, and even DEATH. Increased capillary permeability is caused by the vasoactive substances, such as VASCULAR ENDOTHELIAL GROWTH FACTORS, secreted by the overly-stimulated OVARIES.
Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)
An aggressive lymphoma that develops in HIV-positive patients. There is a significant increase in the incidence of lymphomas associated with the AIDS epidemic. These lymphomas are usually extranodal, most often express a B-cell phenotype and morphologically are classified as Burkitt, diffuse large B-cell, and Hodgkin lymphomas. The prognosis is closely related to the severity of immunodeficiency.
Any disorder affecting blood flow through the veins or arteries outside of the heart.
Hailey-Hailey disease, also known as benign chronic pemphigus, is a rare autosomal dominant cutaneous disorder that usually becomes manifest in the third or fourth decade of life with erythema, vesicles, and erosions involving the body folds, particularly the groin and axillary regions. Other sites of the body, such as the neck, perianal, and submammary regions, may likewise be affected (summary by Poblete-Gutierrez et al., 2004). This disorder was first described by the dermatologist brothers Hailey and Hailey (1939).
Ingrowth of new blood vessels into the cornea.
A combined immunodeficiency primary immune deficiency that is characterized by a more severe defect in both the T- and B-lymphocyte systems.
Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy.
Loss of detectable antigen from the surface of a cell after incubation with antibodies. This is one method in which some tumors escape detection by the immune system. Antigenic modulation of target antigens also reduces the therapeutic effectiveness of treatment by monoclonal antibodies.
A state of elevated cardiac output due to conditions of either increased hemodynamic demand or reduced cardiac oxygen output. These conditions may include ANEMIA; ARTERIOVENOUS FISTULA; THYROTOXICOSIS; PREGNANCY; EXERCISE; FEVER; and HYPOXIA. In time, compensatory changes of the heart can lead to pathological form of high cardiac output and eventual HEART FAILURE.
Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory.
GM1 gangliosidosis is an inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Some researchers classify this condition into three major types based on the age at which signs and symptoms first appear. Although the three types differ in severity, their features can overlap significantly. Because of this overlap, other researchers believe that GM1 gangliosidosis represents a continuous disease spectrum instead of three distinct types.The signs and symptoms of the most severe form of GM1 gangliosidosis, called type I or the infantile form, usually become apparent by the age of 6 months. Infants with this form of the disorder typically appear normal until their development slows and muscles used for movement weaken. Affected infants eventually lose the skills they had previously acquired (developmentally regress) and may develop an exaggerated startle reaction to loud noises. As the disease progresses, children with GM1 gangliosidosis type I develop an enlarged liver and spleen (hepatosplenomegaly), skeletal abnormalities, seizures, profound intellectual disability, and clouding of the clear outer covering of the eye (the cornea). Loss of vision occurs as the light-sensing tissue at the back of the eye (the retina) gradually deteriorates. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. In some cases, affected individuals have distinctive facial features that are described as ""coarse,"" enlarged gums (gingival hypertrophy), and an enlarged and weakened heart muscle (cardiomyopathy). Individuals with GM1 gangliosidosis type I usually do not survive past early childhood.Type II GM1 gangliosidosis consists of intermediate forms of the condition, also known as the late infantile and juvenile forms. Children with GM1 gangliosidosis type II have normal early development, but they begin to develop signs and symptoms of the condition around the age of 18 months (late infantile form) or 5 years (juvenile form). Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, distinctive facial features, or enlarged organs. Type II usually progresses more slowly than type I, but still causes a shortened life expectancy. People with the late infantile form typically survive into mid-childhood, while those with the juvenile form may live into early adulthood.The third type of GM1 gangliosidosis is known as the adult or chronic form, and it represents the mildest end of the disease spectrum. The age at which symptoms first appear varies in GM1 gangliosidosis type III, although most affected individuals develop signs and symptoms in their teens. The characteristic features of this type include involuntary tensing of various muscles (dystonia) and abnormalities of the spinal bones (vertebrae). Life expectancy varies among people with GM1 gangliosidosis type III.
Mucopolysaccharidosis type VII is an autosomal recessive lysosomal storage disease characterized by the inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment (Shipley et al., 1993). MPS VII was the first autosomal mucopolysaccharidosis for which chromosomal assignment was achieved.
A benign or malignant, primary or metastatic neoplasm that affects the brain, meninges, or spinal cord. Representative examples of primary neoplasms include astrocytoma, oligodendroglioma, ependymoma, and meningioma. Representative examples of metastatic neoplasms include carcinoma and leukemia.
An intraventricular neoplasm that originates from the choroid plexus. The vast majority of choroid plexus neoplasms originate from the epithelial layer and include the choroid plexus papilloma, atypical choroid plexus papilloma, and choroid plexus carcinoma.
A macrolide isolated from Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus possesses similar immunosuppressive properties to cyclosporine, but is more potent.
A competitive and reversible histamine H2-receptor antagonist with antacid activity. Nizatidine inhibits the histamine H2-receptors located on the basolateral membrane of the gastric parietal cell, thereby reducing basal and nocturnal gastric acid secretion, resulting in a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli.
A pharmaceutical product equivalent to the brand name drug in dosage, safety, strength, how it is taken, quality, performance, and intended use. The FDA bases evaluations of substitutability, or therapeutic equivalence of a generic drug on scientific evaluation. A generic drug product must contain the identical amounts of the same active ingredient(s) as the brand name product and is expected to have equal effect when substituted for the brand name product.
A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (PHOTOTHERAPY), during the season of recurrence.
Inflammation of the apocrine sweat glands, characterized by redness, itching, pain or swelling of the sweat glands, usually in the axillae or groin.
A neoplastic disease of cats frequently associated with feline leukemia virus infection.
A lymphoid neoplastic disease in cattle caused by the bovine leukemia virus. Enzootic bovine leukosis may take the form of lymphosarcoma, malignant lymphoma, or leukemia but the presence of malignant cells in the blood is not a consistent finding.
Infection caused by bacterial overgrowth in the vagina. Most affected women are asymptomatic. When symptoms occur, they include foul-smelling vaginal discharge, vaginal itching, and burning. Risk factors include sexual activity with multiple partners and the use of vaginal douches and intrauterine devices. Up to a third of cases resolve without treatment. Antibiotic treatment is recommended when symptoms are present and for women that are pregnant at the time of infection.
An unusual benign or malignant neoplasm characterized by the presence of neoplastic large polygonal cells with granular, eosinophilic cytoplasm which contains abundant lysosomes. It was originally thought to be a tumor originating from muscle cells and was named granular cell myoblastoma. Subsequent studies have suggested a derivation from Schwann cells. It affects females more often than males and it usually presents as a solitary mass. A minority of patients have multiple tumors. It can arise from many anatomic sites including the posterior pituitary gland, skin, oral cavity, esophagus, stomach, heart, mediastinum, and breast.
Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.
A synthetic piperidinyl-benzimidazol derivative with antiallergic properties, Astemizole acts as a reversible competitive inhibitor of histamine H1 receptors, with less anticholinergic effects compared to related agents. It is a long-acting, non-sedative antihistaminic used in the treatment of seasonal allergic rhinitis, asthma, allergic conjunctivitis, and chronic idiopathic urticaria. (NCI04)
An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.
A prodrug that is metabolized by intestinal CYP3A4 to the active form fexofenadine, a selective histamine H1-receptor antagonist with antihistaminic and non-sedative effects. Terfenadine's active metabolite competitively binds peripheral H1-receptors, thereby stabilizing an inactive conformation of the receptor. Consequently, usual allergic responses as a result of mast-cell degranulation followed by the release of multiple inflammatory mediators, such as interleukins, prostaglandins, and leukotriene precursors, are blocked, thereby preventing the triggering of pro-inflammatory pathways.
A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties.
A methotrexate derivative with potential antineoplastic activity. Trimetrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylate, with subsequent inhibition of DNA and RNA synthesis. Trimetrexate also exhibits antiviral activity. (NCI04)
A complex systemic syndrome with inflammatory and autoimmune components that affect the skin, fascia, muscle, nerve, blood vessels, lung, and heart. Diagnostic features generally include EOSINOPHILIA, myalgia severe enough to limit usual activities of daily living, and the absence of coexisting infectious, autoimmune or other conditions that may induce eosinophilia. Biopsy of affected tissue reveals a microangiopathy associated with diffuse inflammation involving connective tissue. (From Spitzer et al., J Rheumatol Suppl 1996 Oct;46:73-9; Blackburn WD, Semin Arthritis Rheum 1997 Jun;26(6):788-93)
Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause.
A synthetic PGE2 analog that has an inhibitory effect on gastric acid secretion, a mucoprotective effect, and a postprandial lowering effect on gastrin. It has been shown to be efficient and safe in the treatment of gastroduodenal ulcers.
An antagonist of the neurotransmitter dopamine with potential antineoplastic activity. 6-Hydroxydopamine (6-HOD) can be taken up by selective adrenergic terminals, thereby causing acute degeneration of adrenergic terminals that leads to depletion of norepinephrine, and of dopamine in the dopamine-sensitive sites. This agent is auto-oxidated at physiological pH that leads to the formation of reactive free radicals, thereby leading to cytotoxicity in neural cells. 6-Hydroxydopamine is often used to induce CNS and sympathetic neural lesions that model aging and various nervous disorders in animal systems.
A synthetic methylprostaglandin E1 analog that reduces gastric acid secretion and enhances the gastric mucus-bicarbonate barrier. It is effective in the therapy of gastric ulcers and gives significant protection against NSAID-induced gastric mucosal damage. The drug also prevents cyclosporin A-induced damage to endocrine and exocrine pancreatic secretions. It shows a low order of acute toxicity and there is no evidence of embryotoxicity, fetotoxicity, teratogenicity, or mutagenicity in animal studies.
Gestational diabetes is a disorder characterized by abnormally high blood sugar levels during pregnancy. Affected women do not have diabetes before they are pregnant, and most of these women go back to being nondiabetic soon after the baby is born. The disease has a 30 to 70 percent chance of recurring in subsequent pregnancies. Additionally, about half of women with gestational diabetes develop another form of diabetes, known as type 2 diabetes, within a few years after their pregnancy.Gestational diabetes is often discovered during the second trimester of pregnancy. Most affected women have no symptoms, and the disease is discovered through routine screening at their obstetrician's office. If untreated, gestational diabetes increases the risk of pregnancy-associated high blood pressure (called preeclampsia) and early (premature) delivery of the baby.Babies of mothers with gestational diabetes tend to be large (macrosomia), which can cause complications during birth. Infants whose mothers have gestational diabetes are also more likely to develop dangerously low blood sugar levels soon after birth. Later in life, these individuals have an increased risk of developing obesity, heart disease, and type 2 diabetes.
A propiophenone-derived antidepressant and antismoking agent that inhibits the uptake of DOPAMINE.
A transmissible spongiform encephalopathy of cattle associated with abnormal prion proteins in the brain. Affected animals develop excitability and salivation followed by ATAXIA. This disorder has been associated with consumption of SCRAPIE infected ruminant derived protein. This condition may be transmitted to humans, where it is referred to as variant or new variant CREUTZFELDT-JAKOB SYNDROME. (Vet Rec 1998 Jul 25;143(41):101-5)
A trans-carotenoid pigment widely distributed in nature. The compound is used as an oral suntanning agent and as a food and drug coloring agent. Oral ingestion of the compound causes canthaxanthin retinopathy.
Premature ovarian failure is clearly a heterogeneous disorder. The terms 'hypergonadotropic ovarian failure' and 'hypergonadotropic ovarian dysgenesis' (see ODG1, 233300) have been used to indicate a group of disorders in which amenorrhea associated with elevated levels of serum gonadotropins occurs long before the age of 40 years (Coulam, 1982). Cytogenetic studies of X-chromosome aberrations have suggested that it is mainly the long arm of the X chromosome that is involved in defects of ovulation (Bione et al., 1998). Reviews Rossetti et al. (2017) reviewed the genetics of primary ovarian insufficiency, noting that the significance of this disorder was increasing because of the increasing number of women desiring conception beyond 30 years of age, at which point POF prevalence is more than 1%. Genetic Heterogeneity of Premature Ovarian Failure Mutations in genes identified within a region defined as POF2 (Xq13.3-q21.1) have been found to cause other forms of POF: POF2A (300511) by mutation in the DIAPH2 gene (300108) and POF2B (300604) by mutation in the POF1B gene (300603). See also POF3 (608996), caused by mutation in the FOXL2 gene (605597) on chromosome 3q22; POF4 (see 300510), caused by mutation in the BMP15 gene (300247) on chromosome Xp11; POF5 (611548), caused by mutation in the NOBOX gene (610934) on chromosome 7q35; POF6 (612310), caused by mutation in the FIGLA gene (608697) on chromosome 2p13; POF7 (612964), caused by mutation in the NR5A1 gene (184757) on chromosome 9q33; POF8 (615723), caused by mutation in the STAG3 gene (608489) on chromosome 7q22; POF9 (615724), caused by mutation in the HFM1 gene (615684) on chromosome 1p22; POF10 (612885), caused by mutation in the MCM8 gene (608187) on chromosome 20p12; POF11 (616946), caused by mutation in the ERCC6 gene (609413) on chromosome 10q11; POF12 (616947), caused by mutation in the SYCE1 gene (611486) on chromosome 10q26; POF13 (617442), caused by mutation in the MSH5 gene (603382) on chromosome 6p21; and POF14 (618014), caused by mutation in the GDF9 gene (601918) on chromosome 5q31. In 100 patients with primary or secondary amenorrhea before the age of 40 years, who also exhibited elevated FSH, Bouilly et al. (2016) screened for variants in 19 POF-associated or candidate genes. The authors noted that 8 of the 19 mutation-positive patients carried a genetic defect in more than 1 gene, and that patients with 2 or more variants tended to have a younger age of onset and were more likely have primary rather than secondary amenorrhea. Bouilly et al. (2016) suggested that digenicity and possibly oligogenicity may contribute to POF, noting that this might account for the phenotypic variability and incomplete penetrance that have been observed in patients with POF.
A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of BIOGENIC MONOAMINES in the CENTRAL NERVOUS SYSTEM, and affects multiple neurotransmission systems.
A major core protein of the human immunodeficiency virus encoded by the HIV gag gene. HIV-seropositive individuals mount a significant immune response to p24 and thus detection of antibodies to p24 is one basis for determining HIV infection by ELISA and Western blot assays. The protein is also being investigated as a potential HIV immunogen in vaccines.
A disorder characterized by the deposition of amyloid in the wall of the vessels in the brain.
Abscess of the PSOAS MUSCLES resulting usually from disease of the lumbar vertebrae, with the pus descending into the muscle sheath. The infection is most commonly tuberculous or staphylococcal.
A 2-aminoethyl oxime ether of aralkylketones, with antidepressant, antiobsessive-compulsive, and anxiolytic properties. Fluvoxamine, chemically unrelated to other selective serotonin reuptake inhibitors, selectively blocks serotonin reuptake by inhibiting the serotonin reuptake pump at the presynaptic neuronal membrane. This increases serotonin levels within the synaptic cleft, prolongs serotonergic transmission and decreased serotonin turnover, thereby leading to antidepressant, anxiolytic and antiobsessive-compulsive effects. Fluvoxamine shows no significant affinity for histaminergic, alpha or beta adrenergic, muscarinic, or dopaminergic receptors in vitro.
A serine proteinase inhibitor used therapeutically in the treatment of pancreatitis, disseminated intravascular coagulation (DIC), and as a regional anticoagulant for hemodialysis. The drug inhibits the hydrolytic effects of thrombin, plasmin, and kallikrein, but not of chymotrypsin and aprotinin.
A DIVERTICULUM at the upper end of the ESOPHAGUS through the cricopharyngeal muscle at the junction of the PHARYNX and the esophagus.
An antiarrhythmic agent which exerts a potential- and frequency-dependent block of SODIUM CHANNELS.
One of the ANTI-ARRHYTHMIA AGENTS, it blocks VOLTAGE-GATED SODIUM CHANNELS and slows conduction within the His-Purkinje system and MYOCARDIUM.
Systemic-onset rheumatoid arthritis in adults. It differs from classical rheumatoid arthritis in that it is more often marked by acute febrile onset, and generalized lymphadenopathy and hepatosplenomegaly are more prominent.
In the YIN-YANG system of philosophy and medicine, an insufficiency of body fluid (called yinxu), manifesting often as irritability, thirst, constipation, etc. (The Pinyin Chinese-English Dictionary, 1979).
In the YIN-YANG system of philosophy and medicine, a lack of vital energy (called yangxu in Chinese). It manifests itself in various systemic and organic diseases. (The Pinyin Chinese-English Dictionary, 1979)
A selective and potent serotonin-2 antagonist that is effective in the treatment of a variety of syndromes related to anxiety and depression. The drug also improves the subjective quality of sleep and decreases portal pressure.
Proteus syndrome is characterized by progressive segmental or patchy overgrowth most commonly affecting the skeleton, skin, adipose, and central nervous systems. In most individuals Proteus syndrome has modest or no manifestations at birth, develops and progresses rapidly beginning in the toddler period, and relentlessly progresses through childhood, causing severe overgrowth and disfigurement. It is associated with a range of tumors, pulmonary complications, and a striking predisposition to deep vein thrombosis and pulmonary embolism.
Tumor-like mass in lungs composed of fibrous tissue or granulation tissue with inflammatory cells
A nonspecific tumor-like inflammatory lesion in the ORBIT of the eye. It is usually composed of mature LYMPHOCYTES; PLASMA CELLS; MACROPHAGES; LEUKOCYTES with varying degrees of FIBROSIS. Orbital pseudotumors are often associated with inflammation of the extraocular muscles (ORBITAL MYOSITIS) or inflammation of the lacrimal glands (DACRYOADENITIS).
Aggression towards oneself. [HPO:sdoelken]
A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE.
A self-limited viral infectious disorder caused by the human parvovirus B19. It affects predominantly children and is characterized by the development of a bright red skin eruption in the cheeks. It is followed by a maculopapular skin eruption in the extremities which eventually fades into a lacey pattern.
A phenomenon in which symptoms of a disease are fabricated by an individual other than the patient causing unnecessary, and often painful, physical examinations and treatments. This syndrome is considered a form of CHILD ABUSE, since another individual, usually a parent, is the source of the fabrication of symptoms and presents the child for medical care.
A disorder caused by the presence of autoantibodies directed against phospholipids, causing a hypercoaguable state, which may result in blood clots, stroke, heart attack, and in women, significant pregnancy-related complications, including miscarriage and still birth. The syndrome is often associated with other autoimmune disorders, most commonly lupus erythematosus, and infections, including syphilis and Lyme disease.
Alagille syndrome (ALGS) is a complex multisystem disorder involving primarily the liver, heart, eyes, face, and skeleton. The clinical features are highly variable, even within families. The major clinical manifestations of ALGS are cholestasis, characterized by bile duct paucity on liver biopsy; congenital cardiac defects, primarily involving the pulmonary arteries; posterior embryotoxon in the eye; typical facial features; and butterfly vertebrae. Renal and central nervous abnormalities also occur. Mortality is approximately 10%, with vascular accidents, cardiac disease, and liver disease accounting for most of the deaths.
A recurrent pattern of behavior that is characeterized by the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the person or to others. The repetitive engagement in these behaviors ultimately interferes with functioning in other domains.
The stiff-person syndrome (SPS) is most often an adult-onset sporadic acquired disorder characterized by progressive muscle stiffness with superimposed painful muscle spasms accompanied by electromyographic evidence of continuous motor activity at rest. SPS has been associated with autoimmune disorders, diabetes mellitus, thyrotoxicosis, and hypopituitarism with adrenal insufficiency (George et al., 1984). Approximately 60% of patients with SPS have antibodies to glutamic acid decarboxylase (GAD2, or GAD65; 138275), the rate-limiting enzyme in the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), suggesting an immune-mediated pathogenesis (Folli et al., 1993). Approximately 10% of patients develop SPS as a paraneoplastic neurologic disorder associated with antibodies to amphiphysin (AMPH; 600418), an intracellular protein associated with neuronal synaptic vesicle endocytosis (Burns, 2005). See also congenital stiff-man syndrome, or hereditary hyperexplexia (149400), which is caused by mutations in subunits of the glycine receptor gene (GLRA1, 138491; GLRB, 138492). Meinck and Thompson (2002) provided a detailed review of stiff-person syndrome. They also discussed 2 possibly related conditions, progressive encephalomyelitis with rigidity (PERM), a more severe disorder with other neurologic features, and stiff-limb or stiff-leg syndrome, a focal disorder.
Acute INFLAMMATION of the LIVER in humans; caused by HEPATITIS E VIRUS, a non-enveloped single-stranded RNA virus. Similar to HEPATITIS A, its incubation period is 15-60 days and is enterically transmitted, usually by fecal-oral transmission.
Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.
An unexpected natural death from a cardiac cause within a short time period from the onset of symptoms.
Common coronavirus infection of cats caused by the feline infectious peritonitis virus (CORONAVIRUS, FELINE). The disease is characterized by a long incubation period, fever, depression, loss of appetite, wasting, and progressive abdominal enlargement. Infection of cells of the monocyte-macrophage lineage appears to be essential in FIP pathogenesis.
A collective term for pathological conditions which are caused by the formation of a blood clot (THROMBUS) in a blood vessel, or by blocking of a blood vessel with an EMBOLUS, undissolved materials in the blood stream.
Infections with protozoa of the phylum CILIOPHORA.
A form of LEISHMANIASIS, CUTANEOUS caused by Leishmania aethiopica in Ethiopia and Kenya, L. pifanoi in Venezuela, L. braziliensis in South America, and L. mexicana in Central America. This disease is characterized by massive dissemination of skin lesions without visceral involvement.
Infections with organisms of the genus BLASTOCYSTIS. The species B. hominis is responsible for most infections. Parasitologic surveys have generally found small numbers of this species in human stools, but higher positivity rates and organism numbers in AIDS patients and other immunosuppressed patients (IMMUNOCOMPROMISED HOST). Symptoms include ABDOMINAL PAIN; DIARRHEA; CONSTIPATION; VOMITING; and FATIGUE.
Infections of the BRAIN caused by the protozoan TOXOPLASMA gondii that primarily arise in individuals with IMMUNOLOGIC DEFICIENCY SYNDROMES (see also AIDS-RELATED OPPORTUNISTIC INFECTIONS). The infection may involve the brain diffusely or form discrete abscesses. Clinical manifestations include SEIZURES, altered mentation, headache, focal neurologic deficits, and INTRACRANIAL HYPERTENSION. (From Joynt, Clinical Neurology, 1998, Ch27, pp41-3)
A murine IgG2a monoclonal antibody with immunosuppressive activity. Muromonab-CD3 binds to and inhibits CD3 on the surface of circulating T-lymphocytes; binding of muromonab-CD3 to CD3-positive T cells results in an early activation of this T cell subset, followed by cytokine release, and subsequently inhibition of T cell functions. This agent may cause the opsonization and elimination of CD3-positive T cells from the circulation by mononuclear phagocytes in the liver and spleen. CD3 is part of the functional T cell receptor (TCR) complex, which is necessary for antigen recognition by T cells, and is required for signal transduction.
Abnormally reduced blood carbon dioxide (CO2) level.
Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.
Chimeric molecules resulting from the fusion of recombinant soluble CD4 to the Fc portion of immunoglobulins. These have potential use in the therapy of AIDS since they possess both the gp120-binding and HIV-blocking properties of rCD4 as well as the long plasma half-life and Fc receptor-binding functions of immunoglobulin.
Any agent that inhibits prostaglandin G/H synthase (cyclooxygenase or COX), an enzyme that catalyzes the production of prostanoids, including prostaglandins, prostacyclin and thromboxane, from arachidonic acid. Cyclooxygenase inhibitors are a type of non-steroidal anti-inflammatory drug.
A well-circumscribed mass composed of tuberculous granulation tissue that may occur in the cerebral hemispheres, cerebellum, brain stem, or perimeningeal spaces. Multiple lesions are quite common. Management of intracranial manifestations vary with lesion site. Intracranial tuberculomas may be associated with SEIZURES, focal neurologic deficits, and INTRACRANIAL HYPERTENSION. Spinal cord tuberculomas may be associated with localized or radicular pain, weakness, sensory loss, and incontinence. Tuberculomas may arise as OPPORTUNISTIC INFECTIONS, but also occur in immunocompetent individuals.
Infections with bacteria of the family BACILLACEAE.
Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with the development of the following classic tumors: soft tissue sarcoma, osteosarcoma, pre-menopausal breast cancer, brain tumors, adrenocortical carcinoma (ACC), and leukemias. In addition, a variety of other neoplasms may occur. LFS-related cancers often occur in childhood or young adulthood and survivors have an increased risk for multiple primary cancers. Age-specific cancer risks have been calculated.
Infections with bacteria of the family BACTEROIDACEAE.
A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation.
Infections with bacteria of the genus SERRATIA.
Infections with bacteria of the genus UREAPLASMA.
Infections with bacteria of the family NEISSERIACEAE.
Infections with bacteria of the family PASTEURELLACEAE.
A tick-borne disease characterized by FEVER; HEADACHE; myalgias; ANOREXIA; and occasionally RASH. It is caused by several bacterial species and can produce disease in DOGS; CATTLE; SHEEP; GOATS; HORSES; and humans. The primary species causing human disease are EHRLICHIA CHAFFEENSIS; ANAPLASMA PHAGOCYTOPHILUM; and Ehrlichia ewingii.
Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.
A multisystemic disorder characterized by a sensorimotor polyneuropathy (POLYNEUROPATHIES), organomegaly, endocrinopathy, monoclonal gammopathy, and pigmentary skin changes. Other clinical features which may be present include EDEMA; CACHEXIA; microangiopathic glomerulopathy; pulmonary hypertension (HYPERTENSION, PULMONARY); cutaneous necrosis; THROMBOCYTOSIS; and POLYCYTHEMIA. This disorder is frequently associated with osteosclerotic myeloma. (From Adams et al., Principles of Neurology, 6th ed, p1335; Rev Med Interne 1997;18(7):553-62)
A fungal infection caused by Microsporidia. It occurs in immunocompromised patients, causing diarrhea and wasting.
A formulation for presenting an antigen to induce specific immunologic responses. It consists of an assembly of antigens in multimeric form. The assembly is attached to a matrix with a built-in adjuvant, saponin. ISCOMs induce strong serum antibody responses, and are used as highly immunogenic forms of subunit vaccines.
A rare genetic syndrome characterized by autoantibodies production against more than one endocrine organ. The range of endocrinopathies includes hypoparathyroidism, adrenal insufficiency, hypogonadism, type 1 diabetes mellitus and hypothyroidism.
Acquired degenerative dilation or expansion (ectasia) of normal BLOOD VESSELS, often associated with aging. They are isolated, tortuous, thin-walled vessels and sources of bleeding. They occur most often in mucosal capillaries of the GASTROINTESTINAL TRACT leading to GASTROINTESTINAL HEMORRHAGE and ANEMIA.
Infection with FUNGI of the genus ENCEPHALITOZOON. Lesions commonly occur in the BRAIN and KIDNEY tubules. Other sites of infection in MAMMALS are the LIVER; ADRENAL GLANDS; OPTIC NERVES; RETINA; and MYOCARDIUM.
Inherited disease with characteristics of the development of cysts in the kidneys. The disease rarely causes any noticeable problems until the cysts grow large enough to affect renal function, usually between 30 and 60 years of age. Less commonly, children or older people may have noticeable symptoms. Two different genes are known to cause this disease PKD1 and PKD2.
A disorder characterized by recurrent partial seizures marked by impairment of cognition. During the seizure the individual may experience a wide variety of psychic phenomenon including formed hallucinations, illusions, deja vu, intense emotional feelings, confusion, and spatial disorientation. Focal motor activity, sensory alterations and AUTOMATISM may also occur. Complex partial seizures often originate from foci in one or both temporal lobes. The etiology may be idiopathic (cryptogenic partial complex epilepsy) or occur as a secondary manifestation of a focal cortical lesion (symptomatic partial complex epilepsy). (From Adams et al., Principles of Neurology, 6th ed, pp317-8)
Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method.
Infections caused by bacteria that retain the crystal violet stain (positive) when treated by the gram-staining method.
A culture-specific acute delusional syndrome occurring mostly in the Malay people and Southern Chinese. The syndrome is characterized by the individual's sudden experience of depersonalization depicted by the belief that his penis is shrinking into his abdomen and that he will die when this occurs. Although generally classified as a culture-specific syndrome, koro may be no more than a variant of castration anxiety (ANXIETY, CASTRATION) as it has been described in non-Asian patients.
Vaccines or candidate vaccines containing inactivated HIV or some of its component antigens and designed to prevent or treat AIDS. Some vaccines containing antigens are recombinantly produced.
A condition that is caused by infection with Bartonella, and which is characterized by vascular proliferation, usually in immunocompromised individuals.
A form of inflammatory arthritis that results as a reaction to a bacterial infection outside the joint.
Meningeal inflammation produced by CRYPTOCOCCUS NEOFORMANS, an encapsulated yeast that tends to infect individuals with ACQUIRED IMMUNODEFICIENCY SYNDROME and other immunocompromised states. The organism enters the body through the respiratory tract, but symptomatic infections are usually limited to the lungs and nervous system. The organism may also produce parenchymal brain lesions (torulomas). Clinically, the course is subacute and may feature HEADACHE; NAUSEA; PHOTOPHOBIA; focal neurologic deficits; SEIZURES; cranial neuropathies; and HYDROCEPHALUS. (From Adams et al., Principles of Neurology, 6th ed, pp721-2)
Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots.
Meningitis caused by fungal agents which may occur as OPPORTUNISTIC INFECTIONS or arise in immunocompetent hosts.
A species of facultatively anaerobic, Gram negative, rod shaped bacterium in the phylum Proteobacteria. This species is motile by peritrichous flagella, oxidase, urease and indole negative, catalase positive, reduces nitrate, does not degrade pectate and produces acid from sorbitol. E. cloacae is associated with hospital-acquired urinary and respiratory tract infections and is used in industry for explosives biodegradation.
A process that reduces the level of inorganic precipitate within the organic matrix in the enamel and dentin of the tooth.
An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity.
A localization-related (focal) form of epilepsy characterized by seizures which arise in the FRONTAL LOBE.
A synthetic lipid-lowering agent. Pravastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. Pravastatin lowers plasma cholesterol and lipoprotein levels, and modulates immune responses by suppressing MHC II (major histocompatibility complex II) on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. (NCI04)
A form of partial status epilepticus with simple motor manifestations that are maintained for over one hour, with clonic activity restricted to one body part and recurring at fairly regular intervals.
A condition occurring in untreated or partially treated females with PHENYLKETONURIA when they become pregnant. This may result in damages to the FETUS, including MICROCEPHALY; MENTAL RETARDATION; congenital heart disease; FETAL GROWTH RETARDATION; and CRANIOFACIAL ABNORMALITIES. (From Am J Med Genet 1997 Mar 3;69(1):89-95)
Autosomal recessive polycystic kidney disease (ARPKD) belongs to a group of congenital hepatorenal fibrocystic syndromes and is a cause of significant renal and liver-related morbidity and mortality in children. The majority of individuals with ARPKD present in the neonatal period with enlarged echogenic kidneys. Renal disease is characterized by nephromegaly, hypertension, and varying degrees of renal dysfunction. More than 50% of affected individuals with ARPKD progress to end-stage renal disease (ESRD) within the first decade of life; ESRD may require kidney transplantation. Pulmonary hypoplasia resulting from oligohydramnios occurs in a number of affected infants. Approximately 30% of these infants die in the neonatal period or within the first year of life from respiratory insufficiency or superimposed pulmonary infections. With neonatal respiratory support and renal replacement therapies, the long-term survival of these infants has improved to greater than 80%. As advances in renal replacement therapy and kidney transplantation improve long-term survival, it is likely that clinical hepatobiliary disease will become a major feature of the natural history of ARPKD. In addition, a subset of individuals with this disorder are identified with hepatosplenomegaly; the renal disease is often mild and may be discovered incidentally during imaging studies of the abdomen. Approximately 50% of infants will have clinical evidence of liver involvement at diagnosis although histologic hepatic fibrosis is invariably present at birth. This can lead to progressive portal hypertension with resulting esophageal or gastric varices, enlarged hemorrhoids, splenomegaly, hypersplenism, protein-losing enteropathy, and gastrointestinal bleeding. Other hepatic findings include nonobstructed dilatation of the intrahepatic bile ducts (Caroli syndrome) and dilatation of the common bile duct, which may lead to recurrent or persistent bacterial ascending cholangitis due to dilated bile ducts and stagnant bile flow. An increasing number of affected individuals surviving the neonatal period will eventually require portosystemic shunting or liver transplantation for complications of portal hypertension or cholangitis. The classic neonatal presentation of ARPKD notwithstanding, there is significant variability in age and presenting clinical symptoms related to the relative degree of renal and biliary abnormalities.
A cutaneous infection caused by Mycobacterium ulcerans. It presents with painless nodular swelling of the skin, leading to the formation of necrotizing ulcers.
Finberg et al. (2008) referred to this phenotype as iron-refractory iron deficiency anemia (IRIDA) and reviewed the key features: a congenital hypochromic, microcytic anemia; a very low mean corpuscular erythrocyte volume; a low transferrin saturation; abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron; and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron. The authors noted that although urinary levels of hepcidin (606464) are typically undetectable in individuals with iron deficiency, in 5 individuals with IRIDA urinary hepcidin/creatinine ratios were within or above the normal range.
A kind of anemia in which the volume of the red blood cells is normal.
The Pickering school held that blood pressure has a continuous distribution, that multiple genes and multiple environmental factors determine the level of one's blood pressure just as the determination of stature and intelligence is multifactorial, and that 'essential hypertension' is merely the upper end of the distribution (Pickering, 1978). In this view the person with essential hypertension is one who happens to inherit an aggregate of genes determining hypertension (and also is exposed to exogenous factors that favor hypertension). The Platt school took the view that essential hypertension is a simple mendelian dominant trait (Platt, 1963). McDonough et al. (1964) defended the monogenic idea. See McKusick (1960) and Kurtz and Spence (1993) for reviews. Swales (1985) reviewed the Platt-Pickering controversy as an 'episode in recent medical history.' The Pickering point of view appears to be more consistent with the observations.
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Optic neuritis that occurs in the section of the optic nerve located behind the eyeball.
Abnormal movement characterized by involuntary jerking and writhing affecting the limbs, trunk, and facial muscles.
A functional and/or structural disorder of the brain caused by diseases (e.g. liver disease, kidney disease), medications, chemicals, and injuries.
Group of symptoms related to a forced sexual act
Shivering secondary to a febrile process.
A perceived unpleasant smell given off by the body. [HPO:probinson]
Frequent painful contractions beyond 37 weeks of gestation without advancing into labor or delivery.
Chronic excessive intake of water; it may be from an organic cause, such as the dehydration of diabetes mellitus, diabetes insipidus, or a reaction to medication, or from a psychological cause. When untreated it can lead to water intoxication.
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
An acute and compelling urge to urinate.
A disorder characterized by an electrocardiographic finding of abnormally slow heart rate with its origin in the sinus node. Thresholds for different age, gender, and patient populations exist. (CDISC)
A type of supraventricular tachycardia in which the atria are the principal site of electrophysiologic disturbance. [DDD:dbrown]
A disorder characterized by an electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.
A disorder characterized by an electrocardiographic finding of prolonged PR interval for a specific population. For adults one common threshold is a PR interval greater than 0.20 seconds.
A conduction block of the right branch of the bundle of His. This manifests as a prolongation of the QRS complex (greater than 0.12 s) with delayed activation of the right ventricle and terminal delay on the EKG.
spasm of the blood vessels resulting in decrease in their caliber.
A sensation of breathlessness in the recumbent position, relieved by sitting or standing.
paralysis marked by spasticity of the muscles of the paralyzed part and increases tendon reflexes, due to upper motor neuron lesions.
Inability to initiate changes in activity or movement and to perform ordinary volitional movements rapidly and easily.
A sensation of stinging or heat, not necessarily accompanied by redness or physical signs of irritation.
A state of reduced sensibility and response to stimuli which is distinguished from COMA in that the person can be aroused by vigorous and repeated stimulation. The person is still conscious and can make voluntary movements. It can be induced by CENTRAL NERVOUS SYSTEM AGENTS. The word derives from Latin stupere and is related to stunned, stupid, dazed or LETHARGY.
A state of exceeding restlessness and excessive motor activity associated with mental distress or a feeling of inner tension.
An emotional state of indifference characterized by a lack of interest or concern.
A condition of frequent mood changes associated with excessive emotional reactions.
Abnormal sensitivity to light. This may occur as a manifestation of EYE DISEASES; MIGRAINE; SUBARACHNOID HEMORRHAGE; MENINGITIS; and other disorders. Photophobia may also occur in association with DEPRESSION and other MENTAL DISORDERS.
An acute dystonic reaction with blepharospasm, periorbital twitches, and protracted fixed staring episodes. There may be a maximal upward deviation of the eyes in the sustained fashion. Oculogyric crisis can be triggered by a number of factors including neuroleptic medications.
A sudden movement downward, usually resulting in injury.
Elevated skin lesions associated with the presence of purulent material.
A condition characterized by a reticular or fishnet pattern on the skin of lower extremities and other parts of the body. This red and blue pattern is due to deoxygenated blood in unstable dermal blood vessels. The condition is intensified by cold exposure and relieved by rewarming.
Non-neoplastic tumor-like lesions at joints, developed from the SYNOVIAL MEMBRANE of a joint through the JOINT CAPSULE into the periarticular tissues. They are filled with SYNOVIAL FLUID with a smooth and translucent appearance. A synovial cyst can develop from any joint, but most commonly at the back of the knee, where it is known as POPLITEAL CYST.
An abnormal accumulation of the accumulation of interstitial fluid in the soft tissues of the limbs.
A severe, rapidly fatal reaction occurring most commonly in children following an infectious illness. It is characterized by large, rapidly spreading skin hemorrhages, fever, or shock. Purpura fulminans often accompanies or is triggered by DISSEMINATED INTRAVASCULAR COAGULATION.
A deep skin ulcer with a well defined border, which is usually violet or blue. The ulcer edge is often undermined (worn and damaged) and the surrounding skin is erythematous and indurated. The ulcer often starts as a small papule or collection of papules, which break down to form small ulcers with a so called cat's paw appearance. These coalesce and the central area then undergoes necrosis to form a single ulcer.
A friable, benign vascular neoplasm with lobular capillary architecture that presents as a raised red skin growth.
An idiopathic inflammatory disorder affecting the muscles. It presents with symmetrical proximal muscle weakness and elevated skeletal muscle enzymes.
Inflammation of skin adjacent to an infectious site by autoinoculation; appears as eczematous plaque with or without vesicles.
WHAT: Erythema marginatum. Erythema Marginatum: an evanescent, erythematous rash characteris- tically (though not commonly) seen in the early stages of rheumatic fever. The rash is not limited to rheumatic fever, however, and has also been reported in patients with allergic drug reactions, sepsis and glomerulonephritis. WHY: Although the rash is not pathognomonic of rheumatic fever, its presence is helpful in conjunction with other manifestations of rheumatic fever, particularly carditis with which it is most often associated. HOW: The rash is characterized by pink, evanescent, slightly raised small macules with a sharply demarcated and irregular border. The erythematous areas often have pale centers. The rash commonly occurs over the trunk and inner aspects of the upper arms and thighs, but never on the face. It is non-painful and rarely pruritic, may appear and disappear in a matter of hours only to return, and may be brought out by a hot bath or shower. The rash blanches on pressure, and is a transient rash which tends to migrate from place to place. REFS: 1) Jones criteria (revised) for guidance in the diagnosis of rheumatic fever. Circulation 32:664, 1965. 2) Dictionary of the Rheumatic Diseases, Volume I: Signs and Symptoms. American Rheumatism Association, 1982. (Descriptor #133).
A disease where there is cellular death (necrosis) of bone components due to interruption of the blood supply. [HPO:sdoelken]
A nail condition characterized by spontaneous separation of a fingernail or toenail from its nail bed.
A morphologic finding indicating the presence of plasma cell infiltrates in tissues, or the presence of plasma cells in the peripheral blood.
The presence of a capillary hemangiomas, which are hemangiomas with small endothelial spaces.
A carcinoma that arises from a pre-existing lower grade epithelial lesion, or as a result of a primary carcinoma that has spread to secondary sites, or due to a complication of a cancer treatment.
A clonal (malignant) hematopoietic disorder with an acute onset, affecting the bone marrow and the peripheral blood. The malignant cells show minimal differentiation and are called blasts, either myeloid blasts (myeloblasts) or lymphoid blasts (lymphoblasts).
A condition where damage to the peripheral nervous system (including the peripheral elements of the autonomic nervous system) is associated with chronic ingestion of alcoholic beverages. The disorder may be caused by a direct effect of alcohol, an associated nutritional deficiency, or a combination of factors. Clinical manifestations include variable degrees of weakness; ATROPHY; PARESTHESIAS; pain; loss of reflexes; sensory loss; diaphoresis; and postural hypotension. (From Arch Neurol 1995;52(1):45-51; Adams et al., Principles of Neurology, 6th ed, p1146)
An abnormally increased chloride concentration in the blood.
An abnormally decreased chloride concentration in the blood. [HPO:probinson]
A condition of abnormally high level of PHOSPHATES in the blood, usually significantly above the normal range of 0.84-1.58 mmol per liter of serum.
A condition of an abnormally low level of PHOSPHATES in the blood.
A painful swelling of the breasts due to accumulation of milk in blocked lactating ducts.
Hordeola interna are acute purulent infections affecting the meibomian sebacious glands, often caused by staphylococcus infections. In contrast to chalazia (chronic epithelioid cell granulomatous inflammation of the meibomian gland caused by inflammation of a blocked meibomian gland), hordeola are extremely painfull and can cause extreme local swelling.
Inflammation of the bladder resulting in bloody urine.
Cholecystitis that is persistent and long-standing.
An infectious or non-infectious chronic inflammatory process that affects the prostate gland.
Softening and degeneration of the CARTILAGE.
Abnormally high level of monocytes in the blood.
Pancreatic secretory trypsin inhibitor (79 aa, ~9 kDa) is encoded by the human SPINK1 gene. This protein plays a role in the modulation of trypsin activity.
A non-neoplastic disorder characterized by epithelial and/or myoepithelial tissue growth in the breast lobules. It may be associated with apocrine changes or sclerosis.
A type of aganglionic megacolon in which the aganglionic segment comprises the entire colon.
The use of alcoholic beverages to excess, either on individual occasions (""binge drinking"") or as a regular practice.
Inflammation of the colon that is caused by an alteration in intestinal flora by antibiotic use.
An agent that inhibits platelet aggregation and reduces coagulation in the circulatory system.
Autoimmune polyglandular syndrome type I is characterized by the presence of 2 of 3 major clinical symptoms: Addison disease, and/or hypoparathyroidism, and/or chronic mucocutaneous candidiasis (Neufeld et al., 1981).
Autoimmune polyendocrine syndrome type II (APS2), or Schmidt syndrome, is characterized by the presence of autoimmune Addison disease in association with either autoimmune thyroid disease or type I diabetes mellitus, or both. Chronic candidiasis is not present. APS2 may occur at any age and in both sexes, but is most common in middle-aged females and is very rare in childhood (summary by Betterle et al., 2004). See 240300 for a phenotypic description of autoimmune polyendocrine syndrome type I (APS1).
Inflammation of the skin characterized by the presence of bullae which are filled with fluid.
A condition in which the HEAD of the FETUS is larger than the mother's PELVIS through which the fetal head must pass during a vaginal delivery.
bile acid, usually conjugated with either glycine or taurine; acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine.
A synthetic mast cell stabilizer with anti-inflammatory activity. Cromolyn probably interferes with the antigen-mediated calcium ion influx into mast cells. This prevents mast cell degranulation, resulting in mast cell stabilization and inhibition of the release of inflammatory mediators, such as histamine and leukotrienes, which are involved in type I allergic reactions. Cromolyn also prevents inflammatory mediator release from eosinophils.
bile acid formed by bacterial action from cholate; usually conjugated with glycine or taurine; deoxycholate acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent.
N,alpha-dimethyl-N,2- propynyl phenethylamine, a MAO inhibitor which blocks the conversion of MPTP to MPP+ in animal models of Parkinson's disease, and may therefore have therapeutic potential.
An analogue of the hormone vasopressin with antidiuretic and antihemorrhagic properties. Desmopressin acetate has selective affinity for the V2 receptor and acts on the distal kidney tubule by increasing the cellular permeability thereby stimulating water reabsorption. This antidiuretic agent is used in the treatment of central diabetes insipidus. An unrelated action of desmopressin acetate is to increases circulating factor VIII and is used in patients with haemophilia and von Willebrand's disease.
group of glucose polymers made by certain bacteria; dextrans are used therapeutically as plasma volume expanders and anticoagulants; they are also commonly used in biological experimentation and in industry for a wide variety of purposes.
A sulfhydryl-containing carbamate that is the primary in vivo metabolite of disulfiram. Diethyldithiocarbamate chelates zinc, thereby inhibiting metalloproteinases, thereby preventing the degradation of the extracellular matrix and inhibiting an initial step in cancer metastasis and angiogenesis. A known inhibitor of superoxide dismutase, this agent can either potentiate or protect against cell oxidative damage caused by ionizing radiation, depending on the time of administration. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40247&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40247&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C432"" NCI Thesaurus)
Used generally to describe the process whereby thoughts, attitudes, emotions, or a coordinated set of activities becomes separated from one's personality or mental processes. Compare DISSOCIATIVE DISORDERS.
Indicates a person whose marriage has been legally dissolved and has not remarried.
abuse, overuse, or misuse of a drug by its injection into a vein.
The trans-isomer of clomiphene citrate (CC). Enclomiphene has a higher rate of clearance and is less active than the cis-isomer, cis-clomiphene. Clomiphene citrate has been evaluated for antineoplastic activity against breast cancer. (NCI04)
The orally bioavailable citrate salt of enclomiphene, the trans-isomer of the nonsteroidal triphenylethylene compound clomiphene, with tissue-selective estrogenic and antiestrogenic activities. As a selective estrogen receptor modulator (SERM), enclomiphene binds to hypothalamic estrogen receptors, blocking the negative feedback of endogenous estrogens and stimulating the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus; released GnRH subsequently stimulates the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary, resulting in ovulation. In addition, this agent may bind to estrogen receptors on breast cancer cells, resulting in the inhibition of estrogen-stimulated proliferation in susceptible cell populations.
An infection that is caused by the nematode Enterobius vermicularis; it is characterized predominantly by perianal pruritus.
An alkaloid isolated or derived synthetically from Podophyllum peltatum that can bind to and inhibit topoisomerase II and its function in ligating cleaved DNA molecules, resulting in the accumulation of single- or double-strand DNA breaks, the inhibition of DNA replication and transcription, and apoptotic cell death.
The tartrate salt form of ergotamine, an ergot alkaloid and adrenergic alpha agonist with vasoconstrictor activity. Ergotamine tartrate selectively binds to alpha-adrenergic receptors thereby stimulating vascular smooth muscle and causing vasoconstriction in both arteries and veins. Ergotamine tartrate also blocks serotonin 5-HT1D receptors, thereby also causing vasoconstriction in cerebral blood vessels. Constriction of cerebral blood vessels caused by this agent may reduce the blood flow and pressure in cerebral arteries and may relieve the pain of vascular headaches.
ethane-1-hydroxy-1,1-diphosphonate; a diphosphonate compound that affects calcium metabolism and inhibits the resorption and deposition of hydroxyapatite crystals in bone.
The acetate salt form of flecainide, a synthetic agent derived from trifluoroethoxy-benzamide exhibiting antiarrhythmic and local anesthetic activity. As a class Ic antiarrhythmic that blocks sodium channels, flecainide depresses polarization phase 0 and decreases the induction velocity of the His-Purkinje system. It also decreases phase 4 slope and increases the depolarization threshold.
A derivative of isoniazid, used to treat tuberculosis in the Soviet Union.
A form of ovarian failure, caused by resistance to GONADOTROPINS stimulation. It may be caused by defects in the receptors for FOLLICLE STIMULATING HORMONE or LUTEINIZING HORMONE. It may be due to factors interfering with the actions of gonadotropins, such as antibodies blocking the ligand-receptor interaction.
A vaccine intended to prevent or treat infections caused by human immunodeficiency viruses (HIVs).
Segmental glomerular degeneration with a glassy appearance (hyalinosis) caused by the accumulation of plasma proteins in the glomeruli.
An abnormally decreased level of immunoglobulin in blood.
Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency.
Substances that lower the levels of certain LIPIDS in the BLOOD. They are used to treat HYPERLIPIDEMIAS.
A bisdioxopiperazine with iron-chelating, chemoprotective, cardioprotective, and antineoplastic activities. After hydrolysis to an active form that is similar to ethylenediaminetetraacetic acid (EDTA), dexrazoxane chelates iron, limiting the formation of free radical-generating anthracycline-iron complexes, which may minimize anthracycline-iron complex-mediated oxidative damage to cardiac and soft tissues. This agent also inhibits the catalytic activity of topoisomerase II, which may result in tumor cell growth inhibition.
Glomerulonephritis with electron dense deposits in the glomerular basement membrane; after exclusion of membranous nephropathy caused by malignancy, systemic lupus erythematosus, drugs, or infection. Includes membranous nephropathy associated with autoantibodies to the phospholipase A2 receptor1.
A benign or malignant gastrointestinal stromal tumor with epithelioid morphology..
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. [HPO:probinson]
Reduced ability of the liver to perform its functions.
A group of substances similar to VITAMIN K 1 which contains a ring of 2-methyl-1,4-naphthoquinione and an isoprenoid side chain of varying number of isoprene units. In vitamin K 2, each isoprene unit contains a double bond. They are produced by bacteria including the normal intestinal flora.
The nitrate salt form of miconazole, an antifungal synthetic derivative of imidazole and used in the treatment of candidal skin infections, Miconazole selectively affects the integrity of fungal cell membranes, high in ergosterol content and different in composition from mammalian cells membranes. (NCI04)
The Sanfilippo syndrome, or mucopolysaccharidosis III, is an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate (Esposito et al., 2000). The disorder is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. Type A has been reported (van de Kamp et al., 1981) to be the most severe, with earlier onset and rapid progression of symptoms and shorter survival. Genetic Heterogeneity of Mucopolysaccharidosis Type III MPS III includes 4 types, each due to the deficiency of a different enzyme: heparan N-sulfatase (type A); alpha-N-acetylglucosaminidase (type B; 252920); acetyl CoA:alpha-glucosaminide acetyltransferase (type C; 252930); and N-acetylglucosamine 6-sulfatase (type D; 252940).
Sanfilippo syndrome B is an autosomal recessive lysosomal storage disorder characterized by the accumulation of heparan sulfate. Clinically, patients have progressive neurodegeneration, behavioral problems, mild skeletal changes, and shortened life span. The clinical severity ranges from mild to severe (Chinen et al., 2005). For a phenotypic description and a discussion of genetic heterogeneity of Sanfilippo syndrome, or mucopolysaccharidosis III, see MPS IIIA (252900).
Sanfilippo syndrome comprises several forms of lysosomal storage diseases due to impaired degradation of heparan sulfate. The deficient enzyme in Sanfilippo syndrome C, or MPS IIIC, is an acetyltransferase that catalyzes the conversion of alpha-glucosaminide residues to N-acetylglucosaminide in the presence of acetyl-CoA. For a general phenotypic description and a discussion of genetic heterogeneity of Sanfilippo syndrome, see MPS IIIA (252900).
The mucopolysaccharidoses are a family of lysosomal storage diseases caused by deficiencies of enzymes required for the catabolism of glycosaminoglycans. The defects result in accumulation of excessive intralysosomal glycosoaminoglycans (mucopolysaccharides) in various tissues, causing distended lysosomes to accumulate in the cell and interfere with cell function. Multiple types have been described (Mok et al., 2003).
The phenotypic spectrum of mucopolysaccharidosis IVA (MPS IVA) is a continuum that ranges from a severe and rapidly progressive early-onset form to a slowly progressive later-onset form. Children with MPS IVA have no distinctive clinical findings at birth. The severe form is usually apparent between ages one and three years, often first manifesting as kyphoscoliosis, knock-knee (genu valgum), and pectus carinatum; the slowly progressive form may not become evident until late childhood or adolescence often first manifesting as hip problems (pain, stiffness, and Legg Perthes disease). Progressive bone and joint involvement leads to short stature, and eventually to disabling pain and arthritis. Involvement of other organ systems can lead to significant morbidity, including respiratory compromise, obstructive sleep apnea, valvular heart disease, hearing impairment, visual impairment from corneal clouding, dental abnormalities, and hepatomegaly. Compression of the spinal cord is a common complication that results in neurologic impairment. Children with MPS IVA have normal intellectual abilities at the outset of the disease.
GLB1-related disorders comprise two phenotypically distinct lysosomal storage disorders: GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB). GM1 gangliosidosis includes phenotypes that range from severe to mild. Type I (infantile) begins before age one year; progressive central nervous system dysfunction leads to spasticity, deafness, blindness, and decerebrate rigidity. Life expectancy is two to three years. Type II can be subdivided into the late-infantile form and juvenile form. Type II, late-infantile form begins between ages one and three years; life expectancy is five to ten years. Type II, juvenile form begins between ages three and ten years with insidious plateauing of motor and cognitive development followed by slow regression. Type II may or may not include skeletal dysplasia. Type III begins in the second to third decade with extrapyramidal signs, gait disturbance, and cardiomyopathy; and can be misidentified as Parkinson disease. Intellectual impairment is common late in the disease; skeletal involvement includes short stature, kyphosis, and scoliosis of varying severity. MPS IVB is characterized by skeletal changes, including short stature and skeletal dysplasia. Affected children have no distinctive clinical findings at birth. The severe form is usually apparent between ages one and three years, and the attenuated form in late childhood or adolescence. In addition to skeletal involvement, significant morbidity can result from respiratory compromise, obstructive sleep apnea, valvular heart disease, hearing impairment, corneal clouding, and spinal cord compression. Intellect is normal unless spinal cord compression leads to central nervous system compromise.
Herniation of spinal cord tissue through a defect in a region of the vertebral column. The protrusion of the tissue is flush with the level of the skin surface.
A neoplasm which is characterized by the absence of morphologic features associated with malignancy (severe cytologic atypia, tumor cell necrosis, and high mitotic rate). Benign neoplasms remain confined to the original site of growth and do not metastasize to other anatomic sites.
The development of a neoplasm in response to medical or surgical treatment, induced by the treatment itself.
A rare syndrome characterized by severe watery diarrhea, hypokalemia, and achlorhydria. It is caused by the oversecretion of vasoactive intestinal peptide from the pancreatic islet cells.
A sudden episode of intense fear in a situation in which there is no danger or apparent cause. The panic attack is accompanied by symptoms such as palpitations, sweating and chills or hot flushes. There may be a sensation of dyspnea (being out of breath), chest pain, or abdominal distress. Some indiviudals with panic attacks may experience depersonalization, a fear of going crazy, or a fear of dying.
Sacs or reservoirs created to function in place of the COLON and/or RECTUM in patients who have undergone restorative proctocolectomy (PROCTOCOLECTOMY, RESTORATIVE).
A fibrosarcoma, originally observed in a Plymouth Rock hen, now thought to be an expression of infection by certain viruses of the avian leukosis-sarcoma complex in the family
Indicates a person living apart from his/her spouse by legal arrangement.
Any of several bacterial diseases, usually caused by PASTEURELLA MULTOCIDA, marked by the presence of hemorrhagic areas in the subcutaneous tissues, serous membranes, muscles, lymph glands, and throughout the internal organs. The diseases primarily affect animals and rarely humans.
A constellation of symptoms that include abnormal dryness of the mouth, eyes and other mucous membranes. The condition is seen in patients with Sjogren syndrome, sarcoidosis, amyloidosis, and deficiencies of vitamins A and C.
An elaboration of the known or inferred interactions involved in a signal transduction pathway.
A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)
An inflammatory disorder most often affecting children. It is characterized by the presence of arthritis, salmon-colored rash, spiking fevers, fatigue, and sore throats.
The maleate salt form of timolol, a propanolamine derivative and a non-selective beta-adrenergic antagonist with antihypertensive property. Timolol competitively binds to beta-1-adrenergic receptors in the heart and vascular smooth muscle and beta-2-receptors in the bronchial and vascular smooth muscle, resulting in a decrease in beta-adrenergic stimulation. Beta-1-receptor blockade results in a decrease in resting and exercise heart rate and cardiac output, a decrease in both systolic and diastolic blood pressure, and, possibly, a reduction in reflex orthostatic hypotension. Beta-2-blockade results in an increase in peripheral vascular resistance. The ultimate results include vasodilation, and negative chronotropic and inotropic effects. In addition, timolol reduces intra-ocular pressure possibly by decreasing aqueous humor production by reduction of blood flow to the ciliary processes and cAMP synthesis.
The sodium salt form of tolmetin, an arylalkanoic acid and non-steroidal anti-inflammatory drug (NSAID) with analgesic, anti-inflammatory and antipyretic activities. Although the exact mechanism through which tolmetin exerts its effects has yet to be fully elucidated, this agent appears to inhibit the enzyme prostaglandin synthase. This prevents the formation of prostaglandins from prostaglandin precursors, including the synthesis of the inflammatory prostaglandin E2 (PGE2) from the precursor prostaglandin H2 (PGH2). This prevents prostaglandin-mediated effects, including pain, inflammation and fever.
A measure of the inherent variability of repeated observation measurements of a quantity including quantities evaluated by statistical methods and by other means.
The fat soluble vitamin retinol. Vitamin A binds to and activates retinoid receptors (RARs), thereby inducing cell differentiation and apoptosis of some cancer cell types and inhibiting carcinogenesis. Vitamin A plays an essential role in many physiologic processes, including proper functioning of the retina, growth and differentiation of target tissues, proper functioning of the reproductive organs, and modulation of immune function.
A group of water-soluble vitamins essential for metabolism and normal physiological functions. B6 vitamins, including pyridoxine, pyridoxal, and pyridoxamine, are converted in vivo to pyridoxal phosphate, a cofactor necessary for the synthesis of amino acids, neurotransmitters, and sphingolipids. More than 100 enzymes involved in protein metabolism require vitamin B6 as a cofactor. Vitamin B6 is essential to red blood cell, nervous system, and immune systems functions and helps maintain normal blood glucose levels. Vitamin B6 is found in a wide variety of foods including cereals, beans, meat, poultry, fish, and some fruits and vegetables. (NCI04)
An amino acid derivative. Levocarnitine facilitates long-chain fatty acid entry into mitochondria, delivering substrate for oxidation and subsequent energy production. Fatty acids are utilized as an energy substrate in all tissues except the brain. (NCI04)
An orally available 5-substituted 2-pyrimidinone-2'-deoxyribonucleoside analogue and prodrug of 5-iododeoxyuridine (IUdR), an iodinated analogue of deoxyuridine, with radiosensitizing activity. Upon oral administration, ropidoxuridine (IPdR) is efficiently converted to idoxuridine (IUdR) by a hepatic aldehyde oxidase. In turn, IUdR is incorporated into DNA during replication, thereby sensitizing cells to ionizing radiation by increasing DNA strand breaks. Compared to IUdR, ropidoxuridine is associated with a lower toxicity profile and improved anti-tumor activity.
An alpha-glucosidase inhibitor with antiviral action. Derivatives of deoxynojirimycin may have anti-HIV activity.
A radiopharmaceutical containing the dopamine D2/D3 receptor agonist iodobenzamide (IBZM) labeled with the radionuclide iodine I 123 with dopamine receptor-binding and radioisotopic activities. Upon administration, iodine I 123 iodobenzamide binds to dopamine D2/D3 receptors; subsequently, tissues expressing these receptors can be visualized using single photon emission computed tomography (SPECT). Dopamine receptors are a class of metabotropic G protein-coupled receptors found in the central nervous system (CNS) and neuroendocrine tumors such as pheochromocytoma and paraganglioma.
A prostaglandin F analog used to treat OCULAR HYPERTENSION in patients with GLAUCOMA.
A synthetic derivative of nicotinamide adenine dinucleotide (NAD). Aminothiadiazole competitively inhibits inosine 5-monophosphate dehydrogenase, thereby disrupting the regulation of cell proliferation and differentiation in a number of cells. This agent is also a selective human adenosine A3 receptor antagonist. (NCI04)
A second generation purine nucleoside analog with antineoplastic activity. Clofarabine is phosphorylated intracellularly to the cytotoxic active 5'-triphosphate metabolite, which inhibits the enzymatic activities of ribonucleotide reductase and DNA polymerase, resulting in inhibition of DNA repair and synthesis of DNA and RNA. This nucleoside analog also disrupts mitochondrial function and membrane integrity, resulting in the release of pre-apoptotic factors, including cytochrome C and apoptotic-inducing factors, which activate apoptosis.
A purine nucleoside antimetabolite analogue. Cladribine triphosphate, a phosphorylated metabolite of cladribine, incorporates into DNA, resulting in single-strand breaks in DNA, depletion of nicotinamide adenine dinucleotide (NAD) and adenosine triphosphate (ATP), and apoptosis. Because this agent is resistant to adenosine deaminase, an enzyme that inactivates some antineoplastic agents, it is selectively toxic to lymphocytes and monocytes which exhibit little deoxynucleotide deaminase activity. (NCI04)
A pyrimidine derived compound with antifungal activity.
A cholinergic analogue with glandular secretion stimulatory activity. Cevimeline binds to and activates muscarinic receptors, thereby increasing the secretions in exocrine salivary and sweat glands. This cholinergic agonist also increases the tone of smooth muscle in the gastrointestinal and urinary tracts. Cevimeline is being studied as a treatment for dry mouth caused by radiation therapy to the head and neck.
A second-generation cisplatin analogue with antineoplastic activity. Containing a novel ring structure in which glycolate is bound to the platinum by a bidentate ligand, nedaplatin forms reactive platinum complexes that bind to nucelophillic groups in DNA, resulting in intrastrand and interstrand DNA cross-links, apoptosis and cell death. This agent appears to be less nephrotoxic and neurotoxic compared to both cisplatin and carboplatin.
A ribonucleotide reductase inhibitor with activity against retroviruses. Didox inhibits retrovirus replication by depleting the deoxynucleotides obligatory for synthesis of the proviral DNA intermediate of retrovirus replication.
A semisynthetic derivative of rifamycin with a longer biological half-life than rifampicin.
An indolequinone bioreductive prodrug and analog of mitomycin C with potential antineoplastic and radiosensitization activities. Apaziquone is converted to active metabolites in hypoxic cells by intracellular reductases, which are present in greater amounts in hypoxic tumor cells. The active metabolites alkylate DNA, resulting in apoptotic cell death. This agent displays selectivity activity towards both hypoxic solid tumors, which exhibits higher expression of cytochrome P450 reductase, and well-oxygenated malignant cells that overexpress the bioreductive enzyme NQO1 (NAD(P)H: quinone oxidoreductase). Apaziquone may selectively sensitize hypoxic tumor cells to radiocytotoxicity.
A metabolite formed during the metabolism of 17beta-estradiol by hydroxylation of the carbon at position 4 by cytochrome P450 1B1, with potential carcinogenic activity. The mechanism of action for the tumor promoting activity of 4-hydroxyestradiol (4-OHE2) is not entirely known but this metabolite undergoes metabolic redox cycling with its oxidized quinoid form, estradiol 3,4-quinone, and generates reactive oxygen species (ROS), which induce oxidative DNA damage. 4-OHE2 also activates nuclear factor-kappaB (NF-kB) and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways, and induces the expression of certain genes through activation of the estrogen receptor (ER), which stimulates cellular proliferation in susceptible cells.
A sunscreen blocker. Avobenzone is a topical, broad range UV protector and blocks UVA I, UVA II, and UVB wavelengths, thereby limiting the impact of UV rays on skin. (NCI05)
A prodrug of a bifunctional alkylating, dinitrobenzamide derivative with antineoplastic activity. Tretazicar can be activated by the human enzyme quinone oxidoreductase 2 (NQO2) in the presence of the cosubstrate caricotamide, an analogue of the natural cosubstrate dihydronicotinamide riboside (NRH), which acts as an electron donor. The resulting active, but short-lived metabolite, dinitrobenzamide, leads to DNA replication inhibition and the induction of apoptosis in NQO2 expressing cancer cells. Due to the lack of the natural cosubstrate NRH, NQO2 expression is normally latent but is upregulated in certain types of tumor cells.
An orally-active fluoropyrimidine analogue. Eniluracil inhibits dihydropyrimidine dehydrogenase, the rate-limiting enzyme that catabolizes and inactivates 5-fluorouracil (5-FU) in the liver. Co-administration of ethynyluracil permits the oral administration of 5-FU.
The sodium salt of a synthetic antimetabolite analogue of folate with antineoplastic activity. Emfolin sodium competes for the folate binding site of the enzyme dihydrofolate reductase, resulting in inhibition of tetrahydrofolate synthesis, depletion of nucleotide pools, and inhibition of DNA, RNA and protein synthesis. (NCI04)
A non-nucleoside reverse transcriptase inhibitor. Antimoniotungstate is a mineral condensed ion with a cryptic structure.
The propionate salt form of halobetasol, a synthetic corticosteroid with anti-inflammatory, antipruritic, and vasoconstrictor activities. Halobetasol, a topical steroid, diffuses across cell membranes to interact with cytoplasmic corticosteroid receptors located in both the dermal and intradermal cells, thereby activating gene expression of anti-inflammatory proteins mediated via corticosteroid receptor response element. Specifically, this agent induces phospholipase A2 inhibitory proteins, which inhibit the release of arachidonic acid, thereby inhibiting the biosynthesis of potent mediators of inflammation, such as prostaglandins and leukotrienes. As a result, halobetasol reduces edema, erythema, and pruritus through its cutaneous effects on vascular dilation and permeability.
A potent excitatory amino acid antagonist with a preference for non-NMDA iontropic receptors. It is used primarily as a research tool.
The basic, partial chemical structure of corticosteroid hormones such as cortisone and aldosterone. (NCI04)
Acetate salt of elliptinium, a derivative of the alkaloid ellipticine isolated from species of the plant family Apocynaceae, including Bleekeria vitensis, a plant with anti-cancer properties. As a topoisomerase II inhibitor and intercalating agent, elliptinium stabilizes the cleavable complex of topoisomerase II and induces DNA breakages, thereby inhibiting DNA replication and RNA and protein synthesis.
The lysine salt form of acetylsalicylic acid, a nonsteroidal anti-inflammatory drug (NSAID) with analgesic, antipyretic and anti-inflammatory activities. Like other NSAIDs, aspirin DL-lysine inhibits the activity of cyclooxygenase I and II, resulting in decreased formation of prostaglandins (PGs) and thromboxanes precursors. This leads to decreased PG synthesis by PG synthase. This agent also causes a decrease in the formation of thromboxane A2 synthesis by thromboxane synthase, thereby inhibiting platelet aggregation.
A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.
The hydrochloride salt of alfuzosin, a quinazoline compound with smooth muscle-relaxing activity. Alfuzosin selectively binds to and antagonizes post-synaptic alpha-1-adrenoreceptors in smooth muscle of the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra, initiating relaxation of smooth muscle and resulting in improvement of urine flow and the symptoms of benign prostatic hyperplasia (BPH). This agent also blocks alpha-1-adrenoreceptors in peripheral vascular smooth muscle, resulting in vasodilatation and a decrease in peripheral vascular resistance.
A compound with the chemical formula AlCl3; the anhydrous salt is used as a catalyst in organic chemical synthesis, and hydrated salts are used topically as antiperspirants, and for the management of HYPERHYDROSIS.
The aluminum salt of the fatty acid, stearic acid.
A topoisomerase II inhibitor of the anthrapyrazole family that causes covalent cross-links in DNA of tumor cells.
An amino acid mixture for nutritional support
A benzamide derivative that is used as an antipsychotic agent for the treatment of schizophrenia. It is also used as an antidepressive agent.
An anti-aphthous ulcer drug. Amlexanox inhibits the synthesis and release of inflammatory mediators, including leukotrienes and histamine, from mast cells, neutrophils, and mononuclear cells. Amlexanox also acts as a leukotriene D4 antagonist and a phosphodiesterase inhibitor. Amlexanox decreases the time ulcers take to heal as well as the pain associated with the ulcers.
An ammonium salt with potential antiangiogenic and antitumor activities. Tetrathiomolybdate has been found to deplete systemic copper reserves through an unknown mechanism. This agent has been shown to inhibit the activities of cuproenzymes, including superoxide dismutase 1 (SOD1) and cytochrome c oxidase (COX), which may contribute to its antiangiogenic and antitumor effects.
A synthetic heptapeptide identical to endogenous angiotensin-(1-7) with vasodilator and antiproliferative activities. Therapeutic angiotensin 1-7 may inhibit cyclooxygenase 2 (COX-2) and the production of proinflammatory prostaglandins and may activate the angiotensin-(1-7) receptor Mas, resulting in diminished tumor cell proliferation. Activation of the angiotensin-(1-7) receptor Mas, a G-protein coupled, seven transmembrane protein, may down-regulate the phosphorylation and activation of Erk1 and Erk2 in the Erk1/Erk2 MAPK signaling pathway. In the renin-angiotensin system, the vasodilating activity of angiotensin- (1-7), hydrolysed from angiotensin II by the type I transmembrane metallopeptidase and carboxypeptidase angiotensin converting enzyme 2 (ACE2) in vivo, counteracts the vasoconstricting activity of angiotensin II.
Protein of the annexin family exhibiting lipid interaction and steroid-inducibility.
A synthetic sulfated bis(lactobionic acid amide) derivative and heparin analogue with anticoagulant activity. Aprosulate is made up of two fully sulfated lactobionic acid moieties with a diamine spacer via two amide bonds. This agent inhibits thrombin by antagonizing heparin cofactor II (HCII) and thus prevents thrombin-induced platelet aggregation. It prolongs clotting time.
A substance found in certain plants, including burdock. It has shown antiviral and anticancer effects. Arctigenin belongs to a group of substances called lignans.
An L-leucine derivative of melphalan with antineoplastic activity. Asaley alkylates and crosslinks DNA, resulting in disruption of DNA synthesis. (NCI04)
A dideoxyuridine inhibitor of HIV reverse transcriptase that is related to zidovudine. Navuridine exhibits a relatively short half-life and incomplete oral bioavailability and has not been developed into a clinical drug.
Azimexon (2-cyanaziridinyl-2-carbamoyl-aziridinyl-1-propane) is a derivative of 2-cyanaziridine. Immunostimulant which shows therapeutic effects in tumor models and experimental infections in vitro, enhancing T lymphocyte transformation and phagocytosis. The mode of action of azimexon is unknown. It has been suggested that azimexon may alkylate DNA. In cancer patients it increases leukocytosis, blood active T rosettes, T4/T8 ratio, and is used as an adjuvant to chemotherapy in the treatment of melanoma and myeloma.
The active metabolite of benazepril, a carboxyl-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Once the prodrug benazepril is metabolized to benazeprilat in the liver, benazeprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II, resulting in vasodilation. Benazeprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
The benzoate of a estradiol-chlorambucil conjugate. (NCI)
A dietary sterol similar to cholesterol but with an ethyl group at the 24th carbon of the side chain.
A synthetic quaternary ammonium base derivative, parasympathomimetic Bethanechol is a slowly hydrolyzed muscarinic agonist with no nicotinic effects. Generally used to increase smooth muscle tone, Bethanechol is used to treat reflux esophagitis and to initiate urination after surgery, in urinary infections, or for enlarged prostate. It may cause hypotension, cardiac rate changes, and bronchial spasms. (NCI04)
A mineral compound that is used to treat duodenal and gastric ulcers associated with Helicobacter pylori.
The mesylate salt of bitolterol, a diester sympathomimetic amine with bronchodilator activity. As an ester prodrug, bitolterol is hydrolyzed by esterases to its active metabolite colterol (N-t-butylarterenol). Colterol selectively binds to and activates beta-2 adrenergic receptors in bronchiolar smooth muscle, thereby causing stimulation of adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased intracellular cAMP levels cause relaxation of bronchial smooth muscle. This increases air flow and prevents bronchospasms and may eventually lead to an improvement of airway function.
Cartilage extracted from various parts of a cow and is proposed to stimulate the immune system and inhibit tumor cell growth. It was used in the 1950s and 60s to enhance wound healing. (NCI)
The sodium salt form of bromfenac, a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory activities. Upon ophthalmic administration, bromfenac binds to and inhibits the activity of cyclooxygenase II (COX II), an enzyme which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins (PG). By inhibiting PG formation, bromfenac is able to inhibit PG-induced inflammation, thereby preventing vasodilation, leukocytosis, disruption of the blood-aqueous humor barrier, an increase in vascular permeability and an increase in intraocular pressure (IOP).
The nitrate salt form of butaconazole, a synthetic imidazole derivative with fungistatic properties. Butoconazole nitrate interferes with steroid biosynthesis by inhibiting the conversion of lanosterol to ergosterol, thereby changing the fungal cell membrane lipid composition. This alters cell permeability and leads to growth inhibition. Butaconazole nitrate is active against many dermatophytes and yeasts. It also contains antibacterial effects against some gram-positive organisms.
Protein C-ets-1 (441 aa, ~50 kDa) is encoded by the human ETS1 gene. This protein plays a role in transcriptional regulation that is associated with cell motility, apoptosis induction, cell cycle regulation and immune responses.
A synthetic ergoline derivative and a long-acting dopamine receptor agonist with high affinity for the dopamine D2 receptor. Cabergoline exerts an inhibitory effect on prolactin secretion by acting on dopamine receptors present in pituitary lactotrophs. This drug also binds to dopamine D2 receptors in the corpus striatum, thereby mimicking the actions of dopamine on motor control. Cabergoline also possesses antioxidant and neuroprotective properties due to its free radical scavenging activity. Cabergoline is used in the treatment of Parkinson's disease and in the treatment of hyperprolactinemia.
A colorless crystalline or white powdery organic, tricarboxylic acid occurring in plants, especially citrus fruits, and used as a flavoring agent, as an antioxidant in foods, and as a sequestrating agent. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Phenolic metacyclophanes derived from condensation of PHENOLS and ALDEHYDES. The name derives from the vase-like molecular structures. A bracketed [n] indicates the number of aromatic rings.
A urea peroxide compound that is commonly used in tooth whitening agents; topical anti-infective agents, and earwax remover.
Carbetimer (carboxyimamidate) is a low molecular weight derivatized copolymer of ethylene and maleic anhydride. It has demonstrated antitumor activity against several animal models. It has calcium chelation activity but seems to inhibit growth of sensitive cells by disrupting nucleoside uptake and metabolism.
A semisynthetic, broad-spectrum, fourth-generation aminothiazolyl cephalosporin with antibacterial activity. Cefquinome binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
A succinimide with anticonvulsant properties. Although the exact mechanism of action of methsuximide is unclear, it is thought to increase the seizure threshold and suppress the paroxysmal three-cycle-per-second spike-and-wave pattern seen with absence (petit mal) seizures. The frequency of attacks is reduced by depression of nerve transmission in the motor cortex and elevation of the threshold of the CNS to convulsive stimuli, probably due to direct modification of membrane function in excitable cells and/or alteration of chemically mediated neurotransmission.
The sodium succinate salt form of chloramphenicol, a nitrobenzene derivate and broad-spectrum antibiotic with antibacterial activity. Chloramphenicol sodium succinate reversibly binds to the 50S subunit of bacterial ribosomes, thereby interfering with peptidyl transferase activity in the elongation process of protein synthesis. As a result, this agent prevents bacterial cell growth.
An ester or salt of the bile acid cholic acid that is synthesized in the liver from cholesterol, with surfactant and signaling activities in the liver and intestine. In the intestine, cholate acts as a surfactant that promotes the absorption of dietary lipids and fat-soluble vitamins. In the liver, cholate's surfactant activity facilitates biliary excretion of xenobiotics and metal cations. Cholate binds to nuclear receptors, including farnesoid X receptor (FXR), pregnane X receptor (PXR), and the vitamin D receptor (VDR), which directly modulate gene transcription. Cholate may also be used as a biomarker for hepatotoxicity.
A pro-drug carbocyclic analogue of cytidine with antineoplastic and antiviral activities. Cyclopentenyl cytosine (CPEC) is converted to the active metabolite cyclopentenyl cytosine 5'-triphosphate (CPEC-TP); CPEC-TP competitively inhibits cytidine triphosphate (CTP) synthase, thereby depleting intracellular cytidine pools and inhibiting DNA and RNA synthesis. This agent may also induce differentiation of some tumor cell types. The antiviral activity of this agent is broad-spectrum.
A cytostatic agent that interferes with DNA synthesis.
A prodrug of acyclovir with activity against viruses in the herpesvirus family. Desciclovir is absorbed from the gastrointestinal tract and is converted to acyclovir by xanthine oxidase. Acyclovir is further converted to cyclovir triphosphate by viral thymidine kinase and competitively inhibits viral DNA polymerase by incorporating into the growing viral DNA chain and terminating further polymerization.
A sodium phosphate salt form of Dexamethasone, a synthetic adrenal corticosteroid with potent anti-inflammatory properties. In addition to binding to specific nuclear steroid receptors, dexamethasone also interferes with NF-kB activation and apoptotic pathways. This agent lacks the salt-retaining properties of other related adrenal hormones. (NCI04)
The maleate salt form of dexbrompheniramine, an alkylamine derivative with anticholinergic and sedative properties. Dexbrompheniramine is a histamine H1-receptor antagonist that competes with histamine for the H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels and respiratory tract. The antagonistic action of this agent blocks the activities of endogenous histamine, which subsequently leads to temporary relief from the negative histamine-mediated symptoms of allergic reaction such as bronchoconstriction, vasodilation, increased capillary permeability and spasmodic contractions of gastrointestinal smooth muscle.
A imidazole derivative that is an agonist of ADRENERGIC ALPHA-2 RECEPTORS. It is closely-related to MEDETOMIDINE, which is the racemic form of this compound.
A water-soluble, synthetic aziridinylbenzoquinone with potential antineoplastic activity. Bioactivation of aziridinylbenzoquinone RH1 occurs through the two-electron reduction of the quinone to the hydroquinone by the two-electron quinone reductase DT-diaphorase (DTD). The resultant hydroquinone selectively alkylates and cross-links DNA at the 5'-GNC-3' sequence, inihibiting DNA replication, inducing apoptosis, and inhibiting tumor cell proliferation. DTD is over-expressed in many tumors relative to normal tissue, including lung, colon, breast and liver tumors.
A commercial combination preparation, by Wyeth, containing brompheniramine maleate and phenylpropanolamine hydrochloride, with antihistaminergic and vasoconstrictive properties. Brompheniramine maleate, a propylamine antihistamine binds to and blocks H1 receptors thereby preventing the actions of histamine. Phenylpropanolamine hydrochloride is a decongestant that causes constriction of blood vessels mediated through its alpha-adrenergic signaling, thereby reducing blood flow and improving nasal air flow. Dimetapp is used to relieve nasal congestion and to treat rhinitis.
A synthetic derivative of dithio-ethane sulfonate with uroprotective properties. In the kidney, dimesna undergoes reduction to the free thiol compound, mesna, which reacts chemically with the urotoxic ifosfamide metabolites acrolein and 4-hydroxy-ifosfamide, resulting in their detoxification. This agent also inhibits cyclophosphamide-induced hemorrhagic cystitis.
A sulfonamide class III antiarrhythmic agent and potassium channel blocker. Dofetilide selectively blocks cardiac ion channels of the rapid component of the delayed rectifier potassium current Ikr. This antiarrhythmic agent prolongs cardiac action potential duration and effective refractory period due to delayed repolarization without affecting conduction velocity. This results in a normal sinus rhythm. Dofetilide is used in the treatment of atrial fibrillation and flutter.
A recombinant therapeutic agent which is chemically identical to or similar to an endogenous non-mutated melanocyte differentiation antigen expressed by both normal and malignant melanocytes. Vaccinations with recombinant tyrosinase-related protein-2 may elicit an antitumoral cytotoxic T-cell response against tumor cells and some normal cells that express tyrosinase-related protein-2. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38407&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38407&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C38682"" NCI Thesaurus)
A prazosin-related compound that is a selective alpha-1-adrenergic blocker.
A copolymer conjugate of the antineoplastic anthracycline doxorubicin and the water-soluble polymer N-(2-hydroxypropyl) methacrylamide (HPMA). Doxorubicin, an intercalator and a topoisomerase II inhibitor, prevents DNA replication and ultimately inhibits protein synthesis. This agent also generates oxygen free radicals, resulting in cytotoxic lipid peroxidation of cell membrane lipid. HPMA conjugation enhances the permeability and retention of this agent within the tumor vasculature. Poorly cleared by the lymphatic system, this formulation undergoes increased cleavage by tumor cell lysosomal proteinases, resulting in increased, sustained intracellular concentrations of free doxorubicin. Compared to other doxorubicin-containing formulations, this formulation may exhibit an improved toxicity profile due to the lower concentrations of free doxorubicin to which non-malignant tissues are exposed.
A ring-substituted amphetamine derivative, structurally related to the hallucinogen mescaline, with entactogenic, neurotoxic, and motor-stimulatory activities. 3,4-methylenedioxymethamphetamine (MDMA) produces an acute, rapid enhancement in both the release of serotonin from and the inhibition of serotonin reuptake by serotonergic nerve endings in the brain. Once within the cell, MDMA depletes stores of tryptophan hydroxylase (TPH) via acute oxidative inactivation; in turn, depleted stores of TPH leave cell terminals open to damage from oxidative stress, possibly a source of MDMA neurotoxicity. This agent also induces norepinephrine, dopamine, and acetylcholine release and can act directly on a number of receptors, including alpha 2-adrenergic and 5-hydroxytryptamine (5-HT) 2A receptors. MDMA may suppress the dyskinesia associated with long-term use of L-dopamine (L-DOPA) without affecting the efficacy of L-DOPA treatment.
A deoxythymidine analog with activity against herpes simplex virus. Edoxudine is activated by viral thymidine kinase to the 5'-monophosphate which is further phosphorylated by cellular enzymes to the 5'-triphosphate, a competitive inhibitor of the viral-coded DNA polymerase.
A derivative of the alkaloid ellipticine isolated from species of the plant family Apocynaceae, including Bleekeria vitensis, a plant with anti-cancer properties. As a topoisomerase II inhibitor and intercalating agent, elliptinium stabilizes the cleavable complex of topoisomerase II and induces DNA breakages, thereby inhibiting DNA replication and RNA and protein synthesis.
A selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with CONGESTIVE HEART FAILURE.
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.
The citrate salt of a nonsteroidal triphenylethylene antiestrogen. Chemically related to tamoxifen, toremifene is a selective estrogen receptor modulator (SERM). This agent binds competitively to estrogen receptors, thereby interfering with estrogen activity. Toremifene also has intrinsic estrogenic properties, which is manifested depending on the tissue or species. (NCI04)
A beta-adrenoceptor agonist with potential antidepressant activity. Even though preferentially interacts with beta-adrenergic receptors, flerobuterol may exhibit antidepressant activity. Sustained administration of flerobuterol, similar to other beta-adrenergic agonists, may increase serotonin (5-HT) synthesis, thereby enhance serotonergic neurotransmission, partially through an increased transport of the serotonin precursor (tryptophan) to brain.
The propionate salt form of fluticasone, a synthetic trifluorinated glucocorticoid receptor agonist with antiallergic, antiinflammatory and antipruritic effects. Binding and activation of the glucocorticoid receptor results in the activation of lipocortin that in turn inhibits cytosolic phospholipase A2, which triggers cascade of reactions involved in synthesis of inflammatory mediators, such as prostaglandins and leukotrienes. Secondly, mitogen-activated protein kinase (MAPK) phosphatase 1 is induced, thereby leads to dephosphorylation and inactivation of Jun N-terminal kinase directly inhibiting c-Jun mediated transcription. Finally, transcriptional activity of nuclear factor (NF)-kappa-B is blocked, thereby inhibits the transcription of cyclooxygenase 2, which is essential for prostaglandin production.
A phosphinic acid-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As an ester prodrug, fosinopril is hydrolysed by esterases to its active metabolite fosinoprilat. Fosinoprilat specifically and competitively inhibits angiotensin-converting enzyme thereby decreasing the formation of the potent vasoconstrictor angiotensin II, resulting in diminished vasopressor activity. In addition, angiotensin II-mediated aldosterone secretion by adrenal cortex is decreased, which results in a decrease of sodium retention and an increase in water outflow.
A water-soluble pentacyclic pyrolloquinone analogue of mitoquidone with potential antineoplastic activity. Currently, the mechanism of action of fosquidone is unknown. In vitro studies indicate that this agent does not bind to DNA or inhibit topoisomerases.
An anti-tumor antibiotic isolated from the bacterium Streptomyces pulveraceus. Fostriecin inhibits topoisomerase II catalytic activity, resulting in impaired DNA and RNA synthesis in various malignant cell types. This agent also inhibits serine/threonine protein phosphatase type 2A in some tumor cell types, thereby interfering with cellular proliferation and differentiation. (NCI04)
A compound isolated from the marine sponge Pseudaxinyssa cantharella exhibiting anti-tumor activity. Studies indicate girodazole acts during the elongation/termination steps of protein synthesis, resulting in protein synthesis inhibition. (NCI)
A synthetic decapeptide analog of luteinizing hormone-releasing hormone (LHRH) with antineoplastic activity. Goserelin binds to and activates pituitary gonadotropin releasing hormone (GnRH) receptors. Prolonged administration of goserelin inhibits the secretion of pituitary gonadotropin, thereby decreasing levels of testosterone (in males) and estradiol (in females). Administration of this agent in a depot formulation may result in the regression of sex hormone-sensitive tumors and a reduction in sex organ size and function. (NCI04)
A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC.
The hydrochloride salt form of guanidine, a strong basic compound with parasympathomimetic activity. Guanidine hydrochloride enhances the release of acetylcholine following a nerve impulse and potentiates acetylcholine actions on muscarinic and nicotinic receptors. It also appears to slow the rates of depolarization and repolarization of muscle cell membranes. (NCI05)
A complex macrolide polyether from marine sponge genera, such as Halichondria, Axinella, Phakellia, and Lissodendoryx that binds to tubulin, thereby inhibiting mitosis. (NCI)
A complex mixture of monomeric and aggregated porphyrins with photosensitizing activity. Upon systemic administration, hematoporphyrin derivatives accumulate in tumor cells and, once activated by red laser light (630 nm), in the presence of oxygen, produce singlet oxygen and other reactive oxygen radicals, resulting in local radical-mediated tumor cell death.
A subtype of HLA-DRB beta chains that is associated with the HLA-DR51 serological subtype.
The fumarate salt form of ibutilide, a class III antiarrhythmic agent. Ibutilide exerts its effect by activating a slow, inward, predominately sodium current rather than by blocking outward potassium currents. This results in prolongation of atrial and ventricular action potential duration and refractory periods. Ibutilide slightly decreases the sinus rate and atrioventricular (AV) conduction and produces a dose-related prolongation of the QT interval. (NCI05)
A dibenzothiazepine derivative with antipsychotic property. Quetiapine fumarate antagonizes serotonin activity mediated by 5-HT 1A and 5-HT2 receptors. With a lower affinity, this agent also reversibly binds to dopamine D1 and D2 receptors in the mesolimbic and mesocortical areas of the brain leading to decreased psychotic effects, such as hallucinations and delusions. In addition, quetiapine also binds to other alpha-1, alpha-2 adrenergic and histamine H1 receptors.
A 2-cyanoaziridine derivative with antitumor activity in multiple myeloma. Although its mechanism of action is not clearly known, imexon may induce apoptosis via a pathway involving cleaved caspase-3, caspase-9, and/or caspase-8. Other cytotoxic mechanisms of action of this agent may involve thiol depletion, generation of reactive oxygen species (ROS), and decreases in the mitochondrial membrane potential. (NCI04)
A recombinant human insulin analog with rapid-acting, blood glucose-lowering activity. Insulin aspart, acting faster than regular human insulin, regulates glucose metabolism by binding to insulin receptors on muscle and fat cells, thereby facilitating the cellular uptake of glucose. This lowers blood glucose levels. At the same time, insulin aspart inhibits the liver's conversion of stored glycogen into glucose, which also contributes to lower blood glucose levels. Insulin aspart also inhibits lipolysis in adipose tissue, inhibits proteolysis, and enhances protein synthesis. (NCI05)
One of the six homologous soluble proteins that bind insulin-like growth factors (SOMATOMEDINS) and modulate their mitogenic and metabolic actions at the cellular level.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
A semisynthetic camptothecin derivative that inhibits DNA TOPOISOMERASE I to prevent nucleic acid synthesis during S PHASE. It is used as an antineoplastic agent for the treatment of COLORECTAL NEOPLASMS and PANCREATIC NEOPLASMS.
A fungal alkaloid from Nocardiopsis species, which inhibits protein kinase C. (NCI)
A synthetic liposomal formulation of bis-neodecanoate diaminocyclohexane platinum (NDDP), a third-generation platinum complex analogue of cisplatin, with potential antineoplastic activity. After displacement of the 2 long-chain aliphatic leaving groups (neodecanoic acid), platinum diaminocyclohexane (DACH) complexes become highly reactive and alkylate macromolecules, forming both inter- and intra-stranded DNA cross-linkings and inhibiting DNA synthesis, which results in tumor cell cytotoxicity. Because DNA mismatch-repair (MMR) complexes do not recognize DACH-platinum adducts, DNA repair mechanisms are inhibited, overcoming limitations observed with other platinum-based agents. In addition, the liposomal encapsulation improves the bioavailability of NDDP and reduces its toxicity profile.
An agonist of RECEPTORS, ADRENERGIC ALPHA-2 that is used in veterinary medicine for its analgesic and sedative properties. It is the racemate of DEXMEDETOMIDINE.
A synthetic cannabinoid analogue of delta (9)-tetrahydrocannabinol (delta(9)-THC) with antiemetic and anti-analgesic properties. Although its precise mechanism of action is unknown, levonantradol appears to bind and activate the cannabinoid receptors CB1 and/or CB2. (NCI04)
A novel lipid-lowering agent with a complicated mechanism of action. Lifibrol may affect bile acid metabolism, enhance sterol excretion, reduce cholesterol absorption, or enhance synthesis or sensitivity of the LDL receptors. In studies, its lipid-lowering effects were of a magnitude similar to that of the statins, but unlike statins, it had the ability to lower Lp(a), a risk factor in atherosclerosis.
A polyunsaturated long-chain fatty acid with an 18-carbon backbone and exactly three double bonds. At least 17 different isomers of this compound are recognized.
A centrally acting muscle relaxant, chemically similar to amitriptyline hydrochloride with antidepressant activity. The exact mechanism of action of cyclobenzaprine hydrochloride has not been fully determined. However, it primarily acts at the brain stem to reduce tonic somatic motor activity, influencing both gamma and alpha motor neurons. This leads to a reduction in muscle spasms.
The citrate salt of lithium, a monovalent cation with antimanic activity. Although the exact mechanism is unclear, lithium might exert its mood-stabilizing effect via reduction of catecholamine concentration mediated through transneuronal membrane transport of sodium ion by sodium-potassium-stimulated adenosine triphosphatase (Na-K-ATPase). Alternatively, lithium may decrease cyclic adenosine monophosphate (cAMP) concentrations, which would desensitize hormonal-sensitive adenylyl cyclase receptors. Furthermore, lithium, in recommended dosage, blocks the activity of inositol-1-phosphatase, thereby resulting in the subsequent decrease of postsynaptic second messengers, diacylglycerol and inositol triphosphate, that contribute to chronic cell stimulation by altering electrical activity in the neuron.
A synthetic mast cell stabilizing compound with anti-inflammatory activity. Lodoxamide appears to inhibit the antigen-stimulated calcium transport across the mast cell membrane, thereby inhibiting mast cell degranulation and the release of histamine, leukotrienes, and other substances that cause hypersensitivity reactions. Lodoxamide also inhibits eosinophil chemotaxis. When applied topically to the eye, this drug prevents the symptoms associated with keratitis or conjunctivitis.
The olamine salt form of ciclopirox, a synthetic, broad-spectrum antifungal agent with additional antibacterial and anti-inflammatory activities. Ciclopirox exerts its action by binding to and chelating trivalent cations, such as Fe3+ and Al3+, thereby inhibiting the availability of essential co-factors for enzymes. This may lead to a loss of activity of enzymes that are essential for cellular metabolism, organization of cell wall structure and other crucial cell functions. In addition, ciclopirox exerts its anti-inflammatory activity by inhibiting 5-lipoxygenase and cyclooxygenase (COX).
An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.
An androstadiene derivative corticosteroid that is used as an ANTI-ALLERGIC AGENT for the treatment of inflammatory and allergic eye conditions.
The citrate salt of the element magnesium with cathartic activity. The cathartic action of magnesium cations appears to result, in part, from osmotically mediated water retention, which subsequently stimulates peristalsis. In addition, magnesium ions may also stimulate the activity of nitric oxide (NO) synthase and increase the biosynthesis of the phospholipid proinflammatory mediator platelet activating factor (PAF) in the gut. NO may stimulate intestinal secretion via prostaglandin- and cyclic GMP-dependent mechanisms while PAF produces significant stimulation of colonic secretion and gastrointestinal motility.
A lignan which is structurally similar to secoisolariciresinol with an additional lactone involving the gamma-gamma' carbons; plant lignan that is a dietary precursor to the mammalian lignan enterodiol.
An agent that acts as a link between parties, objects, or actions.
A nonsedating derivative of thiobarbituric acid and a novel catalytic topoisomerase II inhibitor with antineoplastic activity. Merbarone interferes with DNA replication via binding directly to topoisomerase II at a domain that maybe shared by other topoisomerase II cleavage-enhancing agents, ex., etoposide. Its mechanism of action appears to be a novel one, since merbarone does not intercalate DNA nor stabilize DNA-topoisomerase II cleavable complexes.
A boron-carrying compound. After parenteral administration, sodium borocaptate accumulates preferentially in tumor cells. When exposed to neutron irradiation, borocaptate absorbs neutrons and self-destructs releasing short-range alpha radiation and 'recoil' lithium in tumor cells, resulting in alpha radiation-induced tumor cell death. This highly selective, localized radiotargeting of tumor cells, known as boron neutron capture therapy (BNCT), spares adjacent normal tissues. (NCI04)
An agent derived from sulfasalazine, an antiinflammatory agent. Mesalamine may reduce inflammation through inhibition of cyclooxygenase and prostaglandin production. Following rectal or oral administration, only a small amount of mesalamine is absorbed; the remainder, acting topically, reduces bowel inflammation, diarrhea, rectal bleeding and stomach pain. (NCI04)
A natural plant alkyloid with activity against human immunodeficiency viruses (HIV) 1 and 2. Michellamine B inhibits HIV reverse transcriptase (RT) activity and HIV-induced cellular fusion and syncytium formation, thereby inhibiting viral propagation. Michellamine B also inhibits human DNA polymerases alpha and beta.
A positive inotropic cardiotonic agent with vasodilator properties. It inhibits cAMP phosphodiesterase type 3 activity in myocardium and vascular smooth muscle. Milrinone is a derivative of amrinone and has 20-30 times the inotropic potency of amrinone.
An aromatic retinoic acid with antikeratonizing activity. Motretinide is used as a topical agent in the treatment of acne.
A liposomal formulation containing a muramyl dipeptide (MDP) analogue with potential immunomodulatory and antineoplastic activities. Muramyl tripeptide phosphatidylethanolamine (MTP-PE), a derivative of the mycobacterial cell wall component MDP, activates both monocytes and macrophages. Activated macrophages secrete cytokines and induce the recruitment and activation of other immune cells, which may result in indirect tumoricidal effects. Liposomal encapsulation of MTP-PE prolongs its half-life and enhances tissue targeting.
14 carbon straight chain saturated fatty acid common in membrane phospholipids and fatty acylated proteins.
An amsacrine analogue with antineoplastic properties. Asulacrine inhibits the enzyme topoisomerase ll, thereby blocking DNA replication and RNA and protein synthesis.
A synthetic muramyl dipeptide (MDP) analogue with potential immunostimulating and antineoplastic activity. As a derivative of the mycobacterial cell wall component MDP, almurtide activates both monocytes and macrophages. This results in the secretion of cytokines and induces the recruitment and activation of other immune cells, which may result in indirect tumoricidal or cytostatic effects.
A synthetic, aminoester, local, anesthetic agent. At the injection site, chloroprocaine hydrochloride acts by inhibiting sodium influx through binding to specific membrane sodium ion channels in the neuronal cell membranes, restricting sodium permeability, and blocking nerve impulse conduction. This leads to a loss of sensation. Chloroprocaine hydrochloride is short-acting due to rapid hydrolysis by pseudocholinesterase into para-aminobenzoic acid in plasma.
A benzodiazepine non-nucleoside reverse transcriptase inhibitor. In combination with other antiretroviral drugs, nevirapine reduces HIV viral loads and increases CD4 counts, thereby retarding or preventing the damage to the immune system and reducing the risk of developing AIDS.
A nonsteroidal arylsulfonamide with anti-inflammatory properties. Nimesulide inhibits the cyclooxygenase-mediated conversion of arachidonic acid to pro-inflammatory prostaglandins. Modestly selective for COX-2, this agent binds to the enzyme, thereby inactivating it. Nimesulide may inhibit some carcinogenic COX-2-related carcinogenic effects on xenobiotic metabolism, apoptosis, immune surveillance and angiogenesis (overexpressed COX-2 in tumor epithelial cells enhances production of vascular growth factors and the formation of capillary-like networks). (NCI04)
nonionic surfactant with nine repeating ethoxy (oxy-1,2-ethanediyl) groups; a spermatocide, formulated primarily as a component of vaginal foams and creams.
The chloride salt form of oxybutynin, a tertiary amine and anticholinergic agent with antispasmodic activity. Oxybutynin chloride exerts its antimuscarinic effect on bladder smooth muscle by blocking muscarinic receptors in smooth muscle, thereby inhibiting acetylcholine binding. This results in a relaxation of bladder smooth muscle, a reduction of involuntary muscle contractions and delays the initial desire to void.
A mixture containing 2-amino-2-methyl-1-propanol and 8-bromotheophylline (a methylxanthine) in a 1:1 ratio, with mild diuretic activity.
A non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, pentopril is hydrolyzed into its active form pentoprilat, which competitively inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Pentoprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Upon hydrolysis, perindopril is converted to its active form perindoprilat, inhibiting ACE and the conversion of angiotensin I to angiotensin II; consequently, angiotensin II-mediated vasoconstriction and angiotensin II-stimulated aldosterone secretion from the adrenal cortex are inhibited and diuresis and natriuresis ensue.
Poly-glutathione peptides composed of (Glu-Cys)n-Gly where n is two to seven. They are biosynthesized by glutathione gamma-glutamylcysteinyltransferase and are found in many PLANTS; YEASTS; and algae. They sequester HEAVY METALS.
An orally available bromide salt form of pinaverium, a calcium channel blocker (CCB) with antispasmodic activity. Upon oral administration, pinaverium blocks the voltage-dependent calcium channels and inhibits calcium ion influx into the smooth muscle cells located in the gastrointestinal (GI) tract. This prevents smooth muscle contraction and relaxes the GI tract. In addition, pinaverium may both reduce bowel uptake of and facilitate the function of locally active, co-administered drugs.
A crystalline antibiotic fermentation product isolated from the bacterium Streptomyces griseoluteus with antineoplastic activity. Piperazinedione alkylates DNA at the N-7 position of guanine, inhibiting DNA replication and inducing cell cycle arrest.
An inducer of liver peroxisomes and of mitochondrial carmitine acetyltransferase. In an animal model, pirinixil reduced total liver cholesterol as well as estimated total body cholesterol.
An acyloxyalkyl ester prodrug of butyric acid. Pivaloyloxymethylbutyrate inhibits histone deacetylase, resulting in cell differentiation, cell growth inhibition, and apoptosis. (NCI04)
The maleate salt form of dexchlorpheniramine, an alkylamine, and first-generation histamine antagonist with anti-allergic activity. Dexchlorpheniramine maleate competitively blocks H1 receptors, thereby preventing the actions of histamine on bronchial smooth muscle, capillaries and gastrointestinal (GI) smooth muscle. This prevents histamine-induced bronchoconstriction, vasodilation, increased capillary permeability, and GI smooth muscle spasms.
A potassium salt used to replenish ELECTROLYTES, for restoration of WATER-ELECTROLYTE BALANCE, as well as a urinary and systemic alkalizer, which can be administered orally or by intravenous infusion. Formerly, it was used in DIURETICS and EXPECTORANTS.
A powder that dissolves in water, which is administered orally, and is used as a diuretic, expectorant, systemic alkalizer, and electrolyte replenisher.
The dipotassium form of phosphoric acid, that can be used as an electrolyte replenisher and with radio-protective activity. Upon oral administration, potassium phosphate is able to block the uptake of the radioactive isotope phosphorus P 32 (P-32).
The sodium phosphate salt form of prednisolone, a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. As a glucocorticoid receptor agonist, prednisolone sodium phosphate binds to specific intracellular glucocorticoid receptors, and causes the ligand- receptor complex to be translocated to the nucleus where it initiates the transcription of glucocorticoid-responsive genes such as various cytokines and lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both potent mediators of inflammation. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis in sensitive tumor cell populations.
The sodium succinate salt form of prednisolone, a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. After cell surface receptor attachment and cell entry, prednisolone enters the nucleus where it binds to and activates specific nuclear receptors, resulting in an altered gene expression and inhibition of proinflammatory cytokine production. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis in sensitive tumor cells populations. (NCI)
An analogue of cyclosporin-A. Valspodar inhibits p-glycoprotein, the multidrug resistance efflux pump, thereby restoring the retention and activity of some drugs in some drug-resistant tumor cells. This agent also induces caspase-mediated apoptosis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41750&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41750&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1405"" NCI Thesaurus)
A drug that blocks the effects of estrogen.
A tyrosine kinase inhibitor that selectively inhibits epidermal growth factor receptor, epidermal factor-stimulated HER14 cell proliferation, and tumor growth in vivo. (NCI)
Oxazole derivative that acts as an agonist for ALPHA-2 ADRENERGIC RECEPTORS and IMIDAZOLINE RECEPTORS. It is used in the treatment of HYPERTENSION.
A derivative of prednisolone, a synthetic glucocorticoid with anti-inflammatory and immunosuppressive property. Upon binding to the cytosolic glucocorticoid receptor and cell entry, rimexolone activates specific glucocorticoid response elements, resulting in altered gene expression. These include induction of synthesis of anti-inflammatory protein IkappaB-alpha and inhibition of synthesis of nuclear factor kappaB (NFkappa B). As a result, pro-inflammatory cytokine production such as interleukin-1 (IL-1), IL-2 and IL-6 is down-regulated and cytotoxic T-lymphocyte activation inhibited. Therefore, an overall reduction in chronic inflammation and autoimmune reactions may be achieved.
A pyridine and diphosphonic acid derivative that acts as a CALCIUM CHANNEL BLOCKER and inhibits BONE RESORPTION.
A group of organic sulfur-containing nitrites, alkyl thionitrites. S-Nitrosothiols include compounds such as S-NITROSO-N-ACETYLPENICILLAMINE and S-NITROSOGLUTATHIONE.
The bromide salt form of methscopolamine, a quaternary ammonium derivative of scopolamine with anticholinergic properties. Methscopolamine bromide exerts its effect on muscarine receptors in the gastrointestinal tract, thereby blocking the actions of acetylcholine. This leads to an inhibition of gastric secretions and gastrointestinal motility.
A novel semi-synthetic derivative of cyclosporin and a cyclodepsipeptide with chemo-sensitizing activity. SDZ 280-446 is one of the drug resistance-modifying agents that inhibit P-glycoprotein, the multidrug resistance efflux pump, thereby restoring the retention and activities of some drugs in drug-resistant tumor cells.
The biologically active fragment of human growth hormone-releasing factor, consisting of GHRH(1-29)-amide. This N-terminal sequence is identical in several mammalian species, such as human, pig, and cattle. It is used to diagnose or treat patients with GROWTH HORMONE deficiency.
The nitrate salt form of oxiconazole, a broad spectrum imidazole derivative with antifungal activity. Although the exact mechanism of action has yet to be fully elucidated, oxiconazole, like other azole antifungals, most likely inhibits the cytochrome P450-dependent demethylation of lanosterol. This prevents the synthesis of ergosterol which is a crucial component of fungal cell membrane. By disrupting fungal cell membrane synthesis and integrity, oxiconazole alters fungal cell membrane permeability, promotes loss of essential intracellular components and eventually inhibits fungal cell growth.
The hydrochloride salt form of sibutramine, a phenethylamine derivative with appetite depressant property. Sibutramine hydrochloride metabolites M1 and M2 competitively inhibit the reuptake of norepinephrine, serotonin, and to a lesser degree dopamine by pre-synaptic nerve terminals, thereby promoting a sense of satiety, leading to a decrease in calorie intake, and possibly an increase in resting metabolic rate. This agent does not exhibit anticholinergic or antihistaminic effects.
The trihydrate sodium salt of acetic acid with alkalinizing, diuretic and electrolyte replacement properties. Following absorption, sodium acetate generates sodium bicarbonate, thereby raising blood and urine pH. In addition, this agent may increase serum sodium concentration.
The sodium salt form of alginic acid and gum mainly extracted from the cell walls of brown algae, with chelating activity. Upon oral administration, sodium alginate binds to and blocks the intestinal absorption of various radioactive isotopes, such as radium Ra 226 (Ra-226) and strontium Sr 90 (Sr-90).
The sodium salt of BENZOIC ACID. It is used as an antifungal preservative in pharmaceutical preparations and foods. It may also be used as a test for liver function.
The sodium salt of butyrate with potential antineoplastic activity. Butyrate, a short chain fatty acid, competitively binds to the zinc sites of class I and II histone deacetylases (HDACs). This binding affects hyperacetylation of histones, resulting in a modified DNA conformation, which subsequently leads to the uncoiling or relaxing of chromatin. Enhanced accessibility of chromatin to transcription-regulatory complexes leads to increased transcriptional activation of various epigenetically suppressed genes. Butyrate, a HDAC inhibitor, induces cell cycle arrest in G1 or G2/M and also increases the expression of other genes and proteins involved in cellular differentiation and apoptotic signaling.
A trihydroxy bile salt that is used as a digestive aid in dietary supplements. It is used in culture media and in conjunction with PAPAIN and PANCREATIN.
Sodium salts of citric acid that are used as buffers and food preservatives. They are used medically as anticoagulants in stored blood, and for urine alkalization in the prevention of KIDNEY STONES.
The sodium salt of gluconic acid with chelating property. Sodium gluconate chelates and forms stable complexes with various ions, preventing them from engaging in chemical reactions.
A sodium salt of racemic or inactive lactic acid with alkalinizing and electrolyte replenishing property. Upon metabolism, sodium lactate is converted to bicarbonate, thereby increasing plasma bicarbonate, which facilitates removal of hydrogen ion and lactate from blood stream and leads to raised blood pH.
The sodium salt form of phenylacetate with ammonia detoxifying activity. Upon administration, sodium phenylacetate binds to glutamine thereby forming phenylacetylglutamine and is thus excreted by the kidneys. By serving as an alternative to urea for the excretion of waste nitrogen, sodium phenylacetate is able to lower ammonia levels in the blood and prevent hyperammonemia.
A potassium ion exchange resin composed of benzene-diethyl polymer with ethenyl-benzene, sulfonated, sodium salt. Administered as an oral suspension, sodium polystyrene sulfonate lowers serum potassium levels by exchanging its sodium ions for potassium ions. Acting primarily in the large intestine, this agent also exchanges its sodium ions for calcium and magnesium ions, resulting in a decrease in serum calcium and magnesium levels. (NCI04)
An inorganic form of the trace element selenium with potential antineoplastic activity. Selenium, administered in the form of sodium selenite, is reduced to hydrogen selenide (H2Se) in the presence of glutathione (GSH) and subsequently generates superoxide radicals upon reaction with oxygen. This may inhibit the expression and activity of the transcription factor Sp1; in turn Sp1 down-regulates androgen receptor (AR) expression and blocks AR signaling. Eventually, selenium may induce apoptosis in prostate cancer cells and inhibit tumor cell proliferation.
An opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent.
The nitrate salt form of sulconazole, a synthetic imidazole derivative with antifungal property. Sulconazole nitrate inhibits fungal cytochrome P-450 sterol C-14 alpha-demethylation, resulting in the accumulation of fungal 14 alpha-methyl sterols and inhibition of the synthesis of ergosterol, an important component of the fungal cell membrane. Inhibition of ergosterol synthesis leads to a disruption of cell membrane permeability, and ultimately inhibition of cell wall synthesis. In addition, sulconazole nitrate seems to interfere with the autolytic degradation of fungal DNA and RNA.
A sodium salt form of sulfoxone, a water-soluble sulfonamide antibiotic used in the treatment of leprosy.
A synthetic broad-spectrum antibiotic with antibacterial, anticoagulant and potential antiangiogenic activities. Taurolidine, derived from the amino acid taurine, binds to and neutralizes bacterial exotoxins and endotoxins, or lipopolysaccharides (LPS). Taurolidine binding to LPS prevents bacterial adherence to host epithelial cells, thereby prevents bacterial invasion of uninfected host cells. Although the mechanism underlying its antineoplastic activity has not been fully elucidated, it may be related to this agent's anti-adherence property. In addition, taurolidine also promotes apoptosis by inducing various apoptotic factors and suppresses the production of vascular endothelial growth factor (VEGF), a protein that plays an important role in angiogenesis.
A compound extracted from the Pacific yew tree Taxus brevifolia with antineoplastic activity. Paclitaxel binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. This agent also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). (NCI04)
An agent with with antilipidemic activity. In animal models tazasubrate caused a reduction of serum cholesterol consistent with accelerated plasma cholesterol turnover.
A broad spectrum antibiotic used as a second-line antitubercular drug, effective against pulmonary and extrapulmonary tuberculosis. Terizidone has activity against Mycobacterium strains that are resistant to first-line drugs.
An inactive peptide prodrug that is slowly converted in the body to lypressin. It is used to control bleeding of ESOPHAGEAL VARICES and for the treatment of HEPATORENAL SYNDROME.
The hydrochloride salt form of trimethobenzamide, a benzamide derivative with an antiemetic property. Although the mechanism of action is largely unknown, it inhibits the chemoreceptor trigger zone (CTZ), an area in the medulla oblongata through which emetic impulses are conveyed to the vomiting center, thereby suppressing nausea and vomiting.
Tissue inhibitors of metalloproteinase. A family of proteins of around 200 residues that can inhibit enzymes of the metalloprotease type, for example collagenase, by binding to them. (DCB-CB)
A semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata. Topotecan inhibits topoisomerase I activity by stabilizing the topoisomerase I-DNA covalent complexes during S phase of cell cycle, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery.
A mesylate salt form of trioxifene, a nonsteroidal selective estrogen receptor modulator (SERM). Trioxifene competitively inhibits the binding of estradiol to estrogen receptor alpha (ER alpha), resulting in ER alpha-mediated gene expression. Clinical development of Trioxifene has not proceeded because of lack of superior results over tamoxifen and side effect profile. (NCI)
The trisodium salt of a synthetic organic analogue of inorganic pyrophosphate with antiviral activity. Foscarnet selectively blocks the pyrophosphate binding site of herpesvirus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. This agent does not require phosphorylation by thymidine kinase (TK) or other kinases and therefore is active in vitro against herpes simplex virus (HSV) TK deficient mutants and cytomegalovirus (CMV) UL97 mutants. Because foscarnet crosses the blood brain barrier, it may be used in the treatment of viral infections of the CNS.
The hydrochloride salt form of pramoxine, a morpholine derivative with local anesthetic property. Pramocaine hydrochloride decreases the permeability of the neuronal membrane to sodium ions by reversibly binding to and inhibiting voltage-gated sodium channels. This results in stabilization of the membrane and, thereby inhibiting the ionic fluxes required for membrane depolarization, hence resulting in the failure to initiate a propagated action potential and subsequent conduction blockade.
A live attenuated bacteria oral vaccine used to prevent typhoid, which is caused by Salmonella typhi.
An organic, iodinated radiopaque X-ray contrast medium used in diagnostic radiography. The iodine moiety of diatrizoate is not penetrable by X-rays, therefore it blocks the X-ray film exposure by radiation. This makes it possible to distinguish, on X-ray film, body parts that contain diatrizoate meglumine from body parts that do not contain this agent and allows for visualization of different body structures.
A cardiotonic quinolinone derivative, that suppresses cell proliferation and induces apoptosis by inducing the expression of p21, an inhibitor of cyclin dependent kinase activity in p53-mediated cell cycle arrest. (NCI)
The hydrochloride salt form of tetrahydrozoline, an imidazole derivative with sympathomimetic property. Applied locally to the eye or nose, tetrahydrozoline binds to and activates alpha-adrenergic receptors, resulting in vasoconstriction and decreased nasal and ophthalmic congestion.
A phenylalkylamine sympathomimetic amine with appetite depressant property. Phendimetrazine tartrate is a prodrug that is hydrolyzed to the active metabolite phenmetrazine, which competes with norepinephrine and dopamine for their presynaptic transporters, thereby blocks the reuptake of these monoamines at the neuronal junctions. As a result, this prolongs activities of dopamine and norepinephrine and leads to central nervous system (CNS) stimulation and metabolic effects, including appetite-suppression, decreased gastric acid secretion and increased blood pressure.
An alkylsulfonate. Yoshi-864 alkylates and crosslinks DNA, thereby inhibiting DNA replication. (NCI04)
An extract from Mycobacterium tuberculosis (M. tuberculosis) containing the polysaccharide arabinomannan, with potential immunostimulating activity. Upon administration of M. tuberculosis arabinomannan Z-100, this agent may activate the immune system by increasing the expression of various cytokines, such as interferon-gamma (IFNg) and interleukin-12. This inhibits the activity of suppressor T-cells, increases T helper 1 cell (Th1) activity and may restore the balance between Th1/Th2 cells. Additionally, Z-100 may inhibit metastasis and tumor cell proliferation.
A salt produced by the reaction of zinc oxide with acetic acid and used as an astringent, styptic, and emetic.
A nutritional supplement containing the zinc salt form of gluconic acid for the purpose of providing zinc. As an essential trace element, zinc is of key importance in many biological processes, acts as an antioxidant and strengthens the immune system. Although the mechanism of action is not completely known, zinc supplementation may be used to increase immunity against viruses or may interfere with the replication of certain viruses, such as the human papillomavirus (HPV).
Inflammation of the eye tissues posterior to the orbital septum, and generally secondary to an infection spread from adjacent sinuses. Signs and symptoms of the affected eye include sudden loss of vision, erythema, edema, decreased eye movement, and pain. Treatment is conducted via intravenous antibiotics, observation, and surgical intervention when necessary.
Acute inflammation and edema of the larger bronchi caused by viruses or bacteria. Signs and symptoms include cough, sputum production, shortness of breath, and wheezing.
A chronic form of sinusitis. [HPO:probinson]
A mild form of chronic hepatitis causing limited damage to the liver.
Acute inflammation of the GALLBLADDER wall. It is characterized by the presence of ABDOMINAL PAIN; FEVER; and LEUKOCYTOSIS. Gallstone obstruction of the CYSTIC DUCT is present in approximately 90% of the cases.
An acute infection of the bladder. It is usually caused by bacteria. Signs and symptoms include increased frequency of urination, pain or burning during urination, fever, cloudy or bloody urine, and suprapubic pain.
An acute inflammatory process that affects the prostate gland. It is caused by bacteria, most often Escherichia coli, Proteus mirabilis, Klebsiella, and Pseudomonas aeruginosa.
An abnormal growth in the ovary, fallopian tube, or surrounding connective tissue.
A non-metastasizing neoplasm that arises from the penis. Representative examples include hemangioma and lymphangioma.
A congenital anomaly in which the aortic valve has two leaflets. It is associated with mutations in the NOTCH1 gene or the SMAD6 gene, encoding neurogenic locus notch homolog protein 1 and mothers against decapentaplegic homolog 6, respectively. It is a clinically heterogeneous condition, with a high incidence of aortic valve and ascending aortic complications requiring surgery.
A malignant epithelial neoplasm arising from the lips.
A malignant epithelial neoplasm that arises from the cecum and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas.
Inflammation of the cervical lymph nodes.
Blocking of a blood vessel by CHOLESTEROL-rich atheromatous deposits, generally occurring in the flow from a large artery to small arterial branches. It is also called arterial-arterial embolization or atheroembolism which may be spontaneous or iatrogenic. Patients with spontaneous atheroembolism often have painful, cyanotic digits of acute onset.
Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.
A disorder diagnosed in childhood or adolescence age group characterized by aggressive behavior, deceitfulness, destruction of property or violation of rules that is persistent and repetitive, and within a one year period.
A splitting open of an anatomical structure, zone, or organ with the exposure or discharge of its content.
An inherited or acquired disorder that affects the metabolism of the carbohydrates. Representative examples include diabetes mellitus, glycogen storage disease, mucopolysaccharidoses, and lactose intolerance.
A finding in which there is a subnormal amount of an enzyme. Enzymes are proteins that are necessary in certain catabolic processes.
An infection that is caused by Epstein-Barr virus.
A detrimental reaction to a food, beverage, food additive, or compound found in foods that produces symptoms in one or more body organs and systems that is not mediated by an immune reaction.
Blockage of the normal flow of the contents in the stomach.
Stomatitis is an inflammation of the mucous membranes of any of the structures in the mouth.
A finding indicating the presence of blood in the semen.
Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.
An atypical proliferation of atypical melanocytes in the dermal-epidermal junction, without infiltration of the papillary or reticular dermis. The melanocytic proliferation is associated with actinic damage and epidermal atrophy. It usually occurs in the sun-exposed skin of elderly people. It is a form of melanoma in situ.
An acute or chronic, viral or bacterial infectious process that affects the lower respiratory tract.
Fluid that seeps out of one or both nipples of the breast.
A loss of mucous substance of the mouth showing local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. It is the result of a variety of causes, e.g., denture irritation, aphthous stomatitis (STOMATITIS, APHTHOUS); NOMA; necrotizing gingivitis (GINGIVITIS, NECROTIZING ULCERATIVE); TOOTHBRUSHING; and various irritants. (From Jablonski, Dictionary of Dentistry, 1992, p842)
Inflammation of the plantar fascia (aponeurosis) on the bottom of the foot causing heel pain. The etiology of plantar fasciitis remains controversial but is likely to involve a biomechanical imbalance. Though often presenting along with HEEL SPUR, they do not appear to be causally related.
A collection of pus in the area of the rectum.
A Rectocele results from a tear in the rectovaginal septum (which is normally a tough, fibrous, sheet-like divider between the rectum and vagina). Rectal tissue bulges through this tear and into the vagina as a hernia. There are two main causes of this tear: childbirth, and hysterectomy.
Any abnormality of the salivary glands, the exocrine glands that produce saliva.
A circumscribed area of pus or necrotic debris in the skin.
A bacterial infectious process affecting the soft tissues. A severe form caused by anaerobic or aerobic bacteria is associated with soft tissues necrosis and affects the subcutaneous adipose tissue, muscles, fascia, and the skin.
The conversion of mental experiences or states into physical symptoms.
Pneumothorax occurring without traumatic injury to the chest or lung.
A carcinoma arising from squamous bronchial epithelial cells. It may be keratinizing or non-keratinizing. Keratinizing squamous cell carcinoma is characterized by the presence of keratinization, pearl formation, and/or intercellular bridges. Non-keratinizing squamous cell carcinoma is characterized by the absence of keratinization, pearl formation, and intercellular bridges. Cigarette smoking and arsenic exposure are strongly associated with squamous cell lung carcinoma.
A transient visual disturbance that is typically caused by a circulatory, ocular or neurological underlying condition.
Excessive granulation tissue at the base of the umbilicus after separation.
An abnormal increase in the size of nasopharyngeal adenoids.
A neoplastic polyp that arises from the stomach. This category includes intestinal-type adenomatous polyps, gastric-type adenomas, and fundic gland polyps.
Reappearance of cholestasis caused by obstruction within the liver by non-cancerous conditions.
Inflamation of the eyelid due to overactivity of the sebaceous gland. [PMID:10777824]
A benign lung neoplasm characterized by the presence of a fibrovascular stroma lined by cuboidal to columnar cells. Patients are usually asymptomatic and it is incidentally discovered as a pulmonary nodule during chest X-ray examination. Surgical excision is curative.
Hemorrhage into the parenchyma of the cerebellum.
A neoplasm that arises from the glandular epithelium of the colonic mucosa. It is characterized by a villous architectural pattern. The neoplastic glandular cells have dysplastic features.
Inflammation of the conjunctiva in a newborn due to chemical irritation which was acquired postnatally from iatrogenic causes.
Noninfectious variant with a clinical presentation similar to that of the acute disease but with less coryza.
Stenosing tenosynovitis of the abductor pollicis longus and extensor pollicis brevis tendons in the first dorsal wrist compartment. The presenting symptoms are usually pain and tenderness at the radial styloid. The cause is almost always related to OVERUSE INJURY or is associated with RHEUMATOID ARTHRITIS.
A blood clot in a deep vein, predominantly in the lower extremity, but may include the pelvis or upper extremity.
Brain damage related to a lowering of blood glucose below a critical level (around 30 mg/dl), which may lead to confusion, lethargy and delirium followed by seizures and coma. Prolonged hypoglycemia may lead to irreversible brain damage.
An acute inflammatory process affecting the esophageal wall.
Febrile seizures with generalized tonic-clonic semiology, duration less than 15 minutes, and without recurrence within the next 24 hours.
A developmental deformity in which the metaphysis of the FEMUR moves proximally and anteriorly away from FEMUR HEAD (epiphysis) at the upper GROWTH PLATE. It is most common in male adolescents and is associated with a greater risk of early OSTEOARTHRITIS of the hip.
A pathologic tract that connects an opening in the anal canal to the perianal skin. In the vast majority of cases there is a history of perianal abscess.
Hypercalcemia generally develops as a late complication of malignancy; its appearance has grave prognostic significance. It remains unclear, however, whether death is associated with hypercalcemic crisis (uncontrolled or recurrent progressive hypercalcemia) or with advanced disease. Symptoms include central nervous system impairment such as delirium with prominent symptoms of personality change, cognitive dysfunction, disorientation, incoherent speech, and psychotic symptoms such as hallucinations and delusions, smooth muscle hypotonicity, and altered cardiovascular function.
A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).
A benign neoplasm that arises from the lung. It is characterized by the presence of mesenchymal tissues admixed with entrapped respiratory epithelium. The majority of cases are peripheral and asymptomatic. A minority of cases arise endobronchially and present with signs and symptoms of bronchial obstruction. Wedge resection or bronchoplastic resection is usually curative. Recurrence is very rare.
Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms.
Renal damage and impaired renal function secondary to urinary tract obstruction.
Disease or damage involving the SCIATIC NERVE, which divides into the PERONEAL NERVE and TIBIAL NERVE (see also PERONEAL NEUROPATHIES and TIBIAL NEUROPATHY). Clinical manifestations may include SCIATICA or pain localized to the hip, PARESIS or PARALYSIS of posterior thigh muscles and muscles innervated by the peroneal and tibial nerves, and sensory loss involving the lateral and posterior thigh, posterior and lateral leg, and sole of the foot. The sciatic nerve may be affected by trauma; ISCHEMIA; COLLAGEN DISEASES; and other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1363)
A benign neoplasm arising from soft tissue of the ovary. It is characterized by the presence of spindle-shaped fibroblasts.
Twisting of the ovary resulting in the cutoff of the blood supply to the ovary. It may develop in an enlarged or normal ovary and in the vast majority of cases is unilateral. Signs and symptoms include acute lower abdominal pain, nausea, vomiting, and fever.
A congenital anomaly in which the pancreas completely (or sometimes incompletely) encircles the second portion of duodenum and occasionally obstructs the more proximal duodenum.
A partial seizure characterized by impairment or loss of consciousness.
An adenocarcinoma arising from the rectum. It is more frequently seen in populations with a Western type diet and in patients with a history of chronic inflammatory bowel disease. Signs and symptoms include intestinal bleeding, anemia, and change in bowel habits. According to the degree of cellular differentiation, rectal adenocarcinomas are divided into well, moderately, and poorly differentiated. Histologic variants include mucinous adenocarcinoma, signet ring cell carcinoma, medullary carcinoma, serrated adenocarcinoma, cribriform comedo-type adenocarcinoma, and micropapillary adenocarcinoma.
The secondary stage of syphilis typically that is characterized by generalized rash (including palms and soles), mucocutaneous lesions, and lymphadenopathy. It usually begins one to two months after the primary stage.
Increased chance of an incapacity to carry out physiological or psychological daily activities
Inability to clear secretions or obstructions from the respiratory tract to maintain a clear airway.
Increased chance of material into trachea-bronchial passages
Conscious or unconscious attempt to disavow the knowledge or meaning of an event to reduce anxiety and/or fear, leading to the detriment of health.
Lack of interest or engagement in leisure activities
Inadequate family response to problems or difficulties
Behavior of primary person (family member, significant other, or close friend) that disables his or her capacities and the client's capacities to effectively address tasks essential to either person's adaptation to the health challenge.
Increased chance of dehydration or fluid loss.
Excess or deficit in oxygenation and/or carbon dioxide elimination at the alveolar-capillary membrane.
Change in or modification of age specific normal growth standards and/or developmental skills.
Change in or modification of ability to manage health-related needs
Inability of a usually continent person to reach the toilet in time to avoid unintentional loss of urine.
Involuntary loss of urine at somewhat predictable intervals when a specific bladder volume is reached.
Involuntary discharge of URINE that is associated with an abrupt and strong desire to void. It is usually related to the involuntary contractions of the detrusor muscle of the bladder (detrusor hyperreflexia or detrusor instability).
Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.
Exposure to or ingestion of dangerous products
Negative evaluation and/or feelings about one's own capabilities, lasting at least three months.
Development of a negative perception of self-worth in response to a current situation.
Change in or modification of ability to maintain one's image of self
Change in or modification of the response to stimuli
Change in or modification of persons's sexual response
Imbalance in the normal sleep/wake cycle
Difficulty in social interactions related to an impairment of characteristics such as eye contact, smiling, appropriate facial expressions, and body postures and characterized by difficulty in forming peer relationships and forming friendships.
Increase chance of inadequate air for breathing
Change in or modification of thought and cognitive processes
Damage to the mucous membrane, cornea, integumentary system, muscular fascia, muscle, tendon, bone, cartilage, joint capsule, and/or ligament.
Impairment in sensory and motor response, mental representation, and spatial attention of the body, and the corresponding environment, characterized by inattention to one side and overattention to the opposite side. Left-side neglect is more severe and persistent than right-side neglect.
Being or existing in a specified place or at the specified time.
A record of the medical history and physical examination findings for a patient collected at the time of admission.
Localized thickening and tightness of the skin of the fingers or toes.
Depressions on the surface of the nail. This finding may be associated with psoriasis.
WHAT: Gonococcal skin lesions. Gonococcal Skin Lesions: hemorrhagic or vesicopustular skin lesions characteristically seen in disseminated gonococcal infections. WHY: The presence of gonococcal skin lesions in a patient with arthritis is highly suggestive of gonococcal arthritis. HOW: Two types of mature skin lesions are consistently seen in gonococcal bacteremia. One is a hemorrhagic (purpuric) papule. The other is a vesicopustular lesion on an erythematous base. Both lesions begin as pinpoint erythematous macules, and typically appear during the first day of symptoms in association with a febrile episode. The purpuric lesions do not blanch with local pressure and often are found on the palms and the soles. They last about a week gradually fading from a dark blue color to a dark brown and then a light brownish yellow color. The vesicopustular lesions evolve through papular, vesicular and pustular stages reaching a maximum diameter of about 2.5 cm. All these stages may be present at the same time. The mature lesion is elevated, slightly umbilicated and surrounded by an erythematous areola. It usually involutes after 4-5 days. The lesions are usually tender and are located on the distal parts of the extremities. The trunk of the body is generally not involved with either lesion. In some cases the purpuric element predominates, while in others the pustular predominates. Rarely, a third variant, a hemorrhagic bulla, will be the sole skin manifestation of gonococcal bacteremia. REFS: 1) Holmes, KK; Counts, GW and Beaty, HN: Disseminated gonococcal infection. Ann Intern Med 74:979, 1971. 2) Ackerman, AB: Hemorrhagic bullae in gonococcemia. N Engl J Med 282:793, 1970. DN19233-3.
A type of purpuira in which the lesions are raised (and can therefore be appreciated upon palpation).
Edema affecting the region situated around the orbit of the eye.
Pain or discomfort of the scalp elicited by palpation.
A cardiac myxoma arising from the atrium.
A painful asymmetric asynchronous sensory and motor peripheral neuropathy involving isolated damage to at least 2 separate nerve areas; associated with (but not limited to) systemic disorders such as diabetes, vasculitis, amyloidosis, direct tumor involvement, polyarteritis nodosa, rheumatoid arthritis, systemic lupus erythematosus, and paraneoplastic syndromes. It also may be associated with Lyme disease, Wegener's granulomatosis, Sjogren syndrome, cryoglobulinemia, hypereosinophilia, temporal arteritis, scleroderma, sarcoidosis, leprosy, acute viral hepatitis A, and acquired immunodeficiency syndrome.
Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.
Inflammation or degeneration of the sensory nerves.
A sensation of tightness in the neck when attempting to move it, especially after a period of inactivity. Neck stiffness often involves soreness and difficulty moving the neck, especially when trying to turn the head to the side.
Presence of a protracted or persistent infection by a pathogen potentially related to an underlying abnormality of the immune system that is not able to clear the infection.
A small-vessel vasculitis presenting with palpable purpura and urticarial lesions which predate the purpuric lesions most frequently observed on the legs. Systemic symptoms including fever, cough, haemoptysis, sinusitis, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, haematochezia, paraesthesia, weakness, and haematuria may be observed. Can be idiopathic (up to 50% of cases) or secondary to infection, medications (such as antituberculosis medication), collagen vascular diseases, or neoplasms.
Raynaud phenomenon without a known underlying autoimmune disorder.
Sjogren syndrome without a concomitant systemic autoimmune disorder.
Sjogren syndrome that occurs with another systemic autoimmune disorder, such as systemic lupus erythematosus or rheumatoid arthritis.
A rare but severe condition caused by a sudden defective production of adrenal steroids (cortisol and aldosterone). It represents an emergency and may occur at any age. Steroid withdrawal is the most common cause in patients with chronic adrenal insufficiency. A precipitating illness, surgery without adrenal support, pregnancy, any acute or chronic disease, or acute trauma are other potential causes of an acute adrenal crisis. The disorder may result from an acute exacerbation of chronic primary adrenal insufficiency. Laboratory exams show signs of adrenal insufficiency (hypoglycaemia, hyponatraemia and elevated natriuresis, hyperkaliaemia, haemoconcentration, hypochloraemic metabolic acidosis and functional renal failure) confirmed by hypocortisolaemia, increased adrenocorticotropic hormone (ACTH) and an insufficient response to rapid ACTH stimulation testing.
A benign, encapsulated tumor, arising from the follicular cells of the thyroid gland. It may be associated with thyroid hormone secretion but it does not have malignant characteristics.
Increased sensitivity to the adverse effects of alcohol, which can include nasal congestion, skin flushes, heart dysrhythmias, nausea, vomiting, indigestion and headaches.
An abnormality of the systemic arterial tree, which consists of the aorta and other systemic arteries.
An abnormality of the musculoskeletal system that is present at birth or detected in the neonatal period.
Adverse drug effects associated with CHOLINERGIC ANTAGONISTS. Clinical features include TACHYCARDIA; HYPERTHERMIA; MYDRIASIS, dry skin and dry mucous membranes, decreased bowel sounds and urinary retention in peripheral anticholinergic syndrome; and HALLUCINATIONS; PSYCHOSES; SEIZURES; and COMA in central anticholinergic syndrome.
Partial or complete wasting (atrophy) of the skin.
Developmental hypoplasia of the thyroid gland.
A disorder characterized by an electrocardiographic finding of complete failure of atrial electrical impulse conduction to the ventricles. This is manifested on the ECG by disassociation of atrial and ventricular rhythms. The atrial rate must be faster than the ventricular rate. (CDISC)
Birth when a fetus is less than 37 weeks and 0 days gestational age.
Prolongation of the time taken for a standardized skin cut of fixed depth and length to stop bleeding.
An increased amount of nitrogen in the form of urea in the blood.
A malignant neoplasm that arises from the epithelium of any part of the digestive system. Representative examples include colorectal carcinoma, esophageal carcinoma, and pancreatic carcinoma.
A carcinoma arising in the oral cavity. Most oral cavity carcinomas are squamous cell carcinomas of the tongue, buccal mucosa, or gums. Less frequent morphologic variants include mucoepidermoid carcinoma and adenocarcinoma.
An abnormal prolongation (delay) in the time required by whole blood to produce a visible clot.
A type of rigidity in which a muscle responds with cogwheellike jerks to the use of constant force in bending the limb (i.e., it gives way in little, repeated jerks when the muscle is passively stretched).
An abnormally reduced response to stimulation of the cornea (by touch, foreign body, blowing air). The corneal reflex (also known as the blink reflex, normally results in an involuntary blinking of the eyelids.
A laboratory test result which indicates increased levels of creatine phosphokinase in a biological specimen.
A laboratory test result demonstrating an increased concentration of creatinine in a biological specimen.
An abnormality of the cerebrospinal fluid (CSF).
Passage of many stools containing blood.
A reduction in the expected therapeutic effect of a drug due to increased clearance.
A laboratory test result demonstrating an increased concentration of a specific drug.
A condition that is characterized by the presence of generalized edema. Causes include congestive heart failure, liver failure, renal failure, and severe malnutrition.
A buildup of fluid that causes swelling in the soft tissues of the genital area.
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Brain dysfunction or damage resulting from sustained MALIGNANT HYPERTENSION. When BLOOD PRESSURE exceeds the limits of cerebral autoregulation, cerebral blood flow is impaired (BRAIN ISCHEMIA). Clinical manifestations include HEADACHE; NAUSEA; VOMITING; SEIZURES; altered mental status (in some cases progressing to COMA); PAPILLEDEMA; and RETINAL HEMORRHAGE.
A non-neoplastic or neoplastic disorder that affects the endometrium. Representative examples include endometritis, endometrial hyperplasia, and endometrial carcinoma.
Stop of growth at the epiphyseal plate the hyaline cartilage plate in the metaphysis at each end of a long bone, at an earlier than normal age, resulting in growth arrest and shortening of the involved bone.
A reduced erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. A decreased ESR may be seen in polycythemia or in certain blood diseases in which red blood cells have an irregular or smaller shape that causes slower settling.
An increased erythrocyte sedimentation rate (ESR). The ESR a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
A type of cardiac arrhythmia with premature contractions of the HEART VENTRICLES. It is characterized by the premature QRS complex on ECG that is of abnormal shape and great duration (generally >129 msec). It is the most common form of all cardiac arrhythmias. Premature ventricular complexes have no clinical significance except in concurrence with heart diseases.
Renal fibrosis is the consequence of an excessive accumulation of extracellular matrix that occurs in virtually every type of chronic kidney disease.
Myocardial fibrosis is characterized by dysregulated collagen turnover (increased synthesis predominates over unchanged or decreased degradation) and excessive diffuse collagen accumulation in the interstitial and perivascular spaces as well as by phenotypically transformed fibroblasts, termed myofibroblasts.
Increase in the level of the enzyme gamma-glutamyltransferase in the blood, which catalyzes the transfer of a gamma glutamyl group from a gamma glutamyl peptide to another peptide, aminoacids, or water.
A rupture in the wall of any structure of the digestive system caused by traumatic or pathologic processes.
An increased level of gamma globulin (immunoglobulin) in the blood. [HPO:probinson]
An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral or intravenous administration of glucose.
Abnormally high level of neutrophils in the blood.
A finding indicating a faster than normal rate of development.
Stature that is smaller than normal as expected for age.
An decreased concentration of high-density lipoprotein cholesterol in the blood.
Improper body tissue repair due to factors affecting one or more of the phases of wound healing, including hemostasis, inflammation, proliferation, and remodeling.
Hemorrhage and necrosis of the adrenal gland tissue. Bilateral and extensive hemorrhage may lead to acute adrenal insufficiency, shock, and death.
Bleeding within the SKULL, including hemorrhages in the brain and the three membranes of MENINGES. The escape of blood often leads to the formation of HEMATOMA in the cranial epidural, subdural, and subarachnoid spaces.
Bleeding originating in the retroperitoneal area.
An abnormally increased magnesium concentration in the blood.
An decreased concentration of cholesterol in the blood.
Familial male hypogonadism is a highly heterogeneous category from which some disorders such as Reifenstein syndrome (312300), Kallmann syndrome (see 308700), isolated gonadotropin deficiency, and some other entities can be separated. The presence of an autosomal recessive form is suggested by the occurrence of parental consanguinity (Nowakowski and Lenz, 1961).
An abnormally decreased magnesium concentration in the blood.
Adverse reactions that occur initially at the site of injection or infusion. Milder type is confined to a local allergic flare reaction. A more severe reaction is caused by extravasation of VESICANTS from the blood vessel at the site of injection and can cause damage to the surrounding tissue. In tumor flare reaction symptoms involve well beyond the injection site such as an increase in the tumor size and tumor markers levels, bone pain, and HYPERCALCEMIA.
A hole (perforation) in the wall of the small intestine.
A finding characterized by increased cerebrospinal fluid pressure within the skull.
An elevated amount of uptake on the radioactive iodine uptake (RAIU) test, which utilizes a radioisotope of iodine to measure how much iodine the thyroid gland absorbs from the blood. The radioactive marker is measured 4-6 hours and in some cases also 24 hours afteradministration of the radioactive marker.
A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).
An abnormal functionality of the kidney.
disease of the kidney structure called tubule
A laboratory test result indicating an increase in the lactate dehydrogenase concentration of a biological sample.
A clinical term used to describe hyperkeratotic epithelial white patches of the genital mucous membranes.--2004
Disruption of hepatocyte function due to liver injury.
Atypical results found on serum liver enzyme testing, which may indicate significant disease and/or disease progression.
The manifestation of psychotic symptoms, such as hallucinations or delusions, in the presence of mania.
A laboratory finding indicating decreased number of hematopoietic cells in the bone marrow. It may result from decreased proliferation of all or part of the hematopoietic series (erythroid, myeloid, and megakaryocytic). Microscopically, the hematopoietic cells are replaced by adipocytes.
A reduction in the strength of one or more muscles.
A necrotic process affecting the hepatic parenchyma.
A small palpable mass in the subcutaneous tissues.
Complete blockage of blood flow through one of the CORONARY ARTERIES, usually from CORONARY ATHEROSCLEROSIS.
Painful sensation in the gallbladder region.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.
A dull or sharp painful sensation associated with the outer or inner structures of the eyeball, having different causes.
A platelet characterized by a structural or functional abnormality.
Abnormally high cell count in a body fluid.
Abnormally increased excretion of porphyrins in the urine.
A disorder that is related to pregnancy. Representative examples include ectopic pregnancy, toxemia of pregnancy, and gestational trophoblastic tumor.
Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation.
An electrocardiographic finding in which the QT interval not corrected for heart rate is prolonged. Thresholds for different age, gender, and patient populations exist. (CDISC)
Decreased time between the start of the Q wave and the end of the T wave as measured by the electrocardiogram (EKG).
Autonomic nervous system overreaction to stimuli, most commonly after spinal cord injury at a T-5 level and above.
Reduced pigmentation of the fundus, typically generalised. Fundoscopy may reveal a low level pigment in both RPE and choroid with clear visibility of choroidal vessels (pale/albinoid) or low pigment level in the RPE with deep pigment in choroid so that visible choroidal vessels are separated by deeply pigmented zones (tesselated/tigroid).
An increase in the level of aspartate aminotransferase in the blood.
An increase in the level of alanine aminotransferase in the blood.
Skin characterized by the lack of natural or normal moisture.
Narrowing of the lumen of small intestine.
Hyperexcitability of the neuromuscular system related to abnormally low level of calcium in the blood, resulting in carpopedal or generalized spasms.
Formation of a blood clot in the lumen of an artery.
Formation of a blood clot (thrombus) inside a cerebral vein, causing the obstruction of blood flow.
Bleeding from a ruptured blood vessel in a duodenal ulcer.
An ulcerated lesion in the esophageal wall.
A circumscribed inflammatory and necrotic erosive lesion in the mucosa surface of the small intestine.
The presence of renal casts (cylindrical, cigar-shaped structures produced by the kidney in certain disease states) in the urine.
An increase in the overall dimensions or volume of the uterus compared to normal.
A morphologic variant of uterine corpus leiomyoma characterized by the presence of hyalinized or myxoid stroma, edema, cystic changes, hemorrhage, and calcifications.
A carcinoma originating in the lung and the most common lung cancer type in never-smokers. Malignant cells exhibit distinct features such as glandular epithelial, or tubular morphology. Mutations in KRAS, EGFR, BRAF, and ERBB2 genes are associated with this cancer.
A malignant epithelial tumor arising from the esophageal mucosa. Two major histologic types of esophageal carcinoma have been described: squamous cell carcinoma and adenocarcinoma. This type of cancer is associated with excessive ethanol and cigarette usage.
Chronic delayed gastric emptying. Gastroparesis may be caused by motor dysfunction or paralysis of STOMACH muscles or may be associated with other systemic diseases such as DIABETES MELLITUS.
A disease or disorder affecting more than one nerve.
Inflammation of retinal blood vessels as manifested by perivascular sheathing or cuffing, vascular leakage and/or occlusion.
An interruption or alteration in the sensory activity or functions of the nervous system.
A mild inflammatory dermal tissue reaction; it can be caused by physical contact with an irritant or can be a local response to a systemic trigger.
Difficulty in beginning the process of urination.
An infection that is caused by certain species of Rickettsia or Borrelia, which are transmitted to humans from infected lice; it is characterized by sudden fever, chills, headaches, myalgia, arthralgia, nausea, and possibly a rash. Symptoms usually persist for two to nine days, then disappear, with recurrence after several weeks if the patient remains untreated.
A chronic, fungal, subcutaneous infection endemic in rural regions in South America and Central America. The causal organism is Lacazia labol.
An infection that is caused by the intestinal fluke Heterophyes heterophyes, which is most commonly found in Asia, the Middle East, and Africa, and which is transmitted via consumption of contaminated raw or undercooked fish. Symptoms typically range from asymptomatic to intermittent abdominal pain and diarrhea, with occasional ectopic infection.
Joint disorders that are characterized by accumulation of microcrystals in and around the joint including in the SYNOVIAL FLUID. They are classified according to the chemical nature of the crystals such as CALCIUM PYROPHOSPHATE; basic CALCIUM PHOSPHATES; and monosodium urate (see URIC ACID).
Trisomy 13, also called Patau syndrome, is a chromosomal condition associated with severe intellectual disability and physical abnormalities in many parts of the body. Individuals with trisomy 13 often have heart defects, brain or spinal cord abnormalities, very small or poorly developed eyes (microphthalmia), extra fingers or toes, an opening in the lip (a cleft lip) with or without an opening in the roof of the mouth (a cleft palate), and weak muscle tone (hypotonia). Due to the presence of several life-threatening medical problems, many infants with trisomy 13 die within their first days or weeks of life. Only five percent to 10 percent of children with this condition live past their first year.
Trisomy 18, also called Edwards syndrome, is a chromosomal condition associated with abnormalities in many parts of the body. Individuals with trisomy 18 often have slow growth before birth (intrauterine growth retardation) and a low birth weight. Affected individuals may have heart defects and abnormalities of other organs that develop before birth. Other features of trisomy 18 include a small, abnormally shaped head; a small jaw and mouth; and clenched fists with overlapping fingers. Due to the presence of several life-threatening medical problems, many individuals with trisomy 18 die before birth or within their first month. Five to 10 percent of children with this condition live past their first year, and these children often have severe intellectual disability.
Abdominal symptoms after removal of the GALLBLADDER. The common postoperative symptoms are often the same as those present before the operation, such as COLIC, bloating, NAUSEA, and VOMITING. There is pain on palpation of the right upper quadrant and sometimes JAUNDICE. The term is often used, inaccurately, to describe such postoperative symptoms not due to gallbladder removal.
WHAT: Chorea. Chorea (Sydenham's): a neurological disorder characterized by purposeless, rapid, involuntary movements, emotional lability, and muscular weakness. WHY: Sydenham's chorea is seen in rheumatic fever. The chorea may be associated with other rheumatic manifestations or it may present as the sole expression of rheumatic fever. HOW: Typically, the onset of chorea is gradual, with irritability, uncooperativeness, fits of anger, crying, and inappropriate behavior present before the choreiform movements are noted. The movements are rapid and jerky, unlike the slower, rhythmic motion seen in athetosis. Characteristically, on raising his arms above the head, the patient turns the arms so as to oppose the backs of the hands. The patient is unable to sustain a tetanic muscular contraction. On squeezing an examiner's hand the patient can only provide a repetitive, spasmodic grip which is overly pronated and is similar to the motion of milking a cow (milk-maid's grip). The patient's facial expression alternates between frowning, grinning and grimacing. His tongue darts in and out of his mouth. His speech is slurred and vacillates between a halting and an explosive rhythm. The deep tendon reflexes tend to be pendular, i.e., when the knee jerk is elicited with the patient sitting, the leg swings back and forth four or five times like a pendulum, rather than one or two times as in a normal person. Chorea is most common prior to puberty, and in females. It is occasionally seen in adult women but never in adult men. REFS: 1) Jones criteria (revised) for guidance in the diagnosis of rheumatic fever. Circulation 32:664, 1965. 2) Cooper, IS: Involuntary Movement Disorders. New York: Hoeber, 1969.
A rare movement disorder of unknown etiology, characterized by painful, involuntary turns of the head to the right, left, upwards, or downwards.
Processes and symptomatic effects resulting from abstinence from a chemical agent or medication. Used for human or animal populations.
Degenerative changes to the RETINA due to HYPERTENSION.
An abnormality of conjugate lateral gaze in which the affected eye shows impairment of adduction. The pathognomonic clinical sign of internuclear ophthalmoplegia is an impaired adduction while testing horizontal saccades on the side of the lesion in the ipsilateral medial longitudinal fascicule.
A form of glaucoma in which chronic optic nerve damage and loss of vision normally attributable to buildup of intraocular pressure occurs despite prevailing conditions of normal intraocular pressure.
Painful sensation in one side of the abdomen between menstrual cycles, around the time of the discharge of the ovum from the ovarian follicle.
Failure of secretion of milk following childbirth associated with an inability to breastfeed an infant.
Greater than 20 hours of labor in nulliparous women and greater than 14 hours in parous women.
Cyclic vomiting syndrome is a disorder that causes recurrent episodes of nausea, vomiting, and tiredness (lethargy). This condition is diagnosed most often in young children, but it can affect people of any age.The episodes of nausea, vomiting, and lethargy last anywhere from an hour to 10 days. An affected person may vomit several times per hour, potentially leading to a dangerous loss of fluids (dehydration). Additional symptoms can include unusually pale skin (pallor), abdominal pain, diarrhea, headache, fever, and an increased sensitivity to light (photophobia) or to sound (phonophobia). In most affected people, the signs and symptoms of each attack are quite similar. These attacks can be debilitating, making it difficult for an affected person to go to work or school.Episodes of nausea, vomiting, and lethargy can occur regularly or apparently at random, or can be triggered by a variety of factors. The most common triggers are emotional excitement and infections. Other triggers can include periods without eating (fasting), temperature extremes, lack of sleep, overexertion, allergies, ingesting certain foods or alcohol, and menstruation.If the condition is not treated, episodes usually occur four to 12 times per year. Between attacks, vomiting is absent, and nausea is either absent or much reduced. However, many affected people experience other symptoms during and between episodes, including pain, lethargy, digestive disorders such as gastroesophageal reflux and irritable bowel syndrome, and fainting spells (syncope). People with cyclic vomiting syndrome are also more likely than people without the disorder to experience depression, anxiety, and panic disorder. It is unclear whether these health conditions are directly related to nausea and vomiting.Cyclic vomiting syndrome is often considered to be a variant of migraines, which are severe headaches often associated with pain, nausea, vomiting, and extreme sensitivity to light and sound. Cyclic vomiting syndrome is likely the same as or closely related to a condition called abdominal migraine, which is characterized by attacks of stomach pain and cramping. Attacks of nausea, vomiting, or abdominal pain in childhood may be replaced by migraine headaches as an affected person gets older. Many people with cyclic vomiting syndrome or abdominal migraine have a family history of migraines.Most people with cyclic vomiting syndrome have normal intelligence, although some affected people have developmental delay or intellectual disability. Autism spectrum disorder, which affects communication and social interaction, have also been associated with cyclic vomiting syndrome. Additionally, muscle weakness (myopathy) and seizures are possible. People with any of these additional features are said to have cyclic vomiting syndrome plus.
A severe intermittent and spasmodic pain in the lower back radiating to the groin, scrotum, and labia which is most commonly caused by a kidney stone (RENAL CALCULUS) passing through the URETER or by other urinary track blockage. It is often associated with nausea, vomiting, fever, restlessness, dull pain, frequent urination, and HEMATURIA.
Increased blood pressure in the arteries of the lungs; the etiology is unknown.
A disorder characterized by an electrocardiographic finding of a high ventricular rate (180 to 250 beats per minute) with a regular rhythm and large oscillating sine wave-like complexes occurring as a result of QRS complexes and T waves being merged. The P wave is not visible.
A non-neoplastic or neoplastic disorder affecting the trigeminal nerve (fifth cranial nerve).
A non-neoplastic or neoplastic disorder affecting the vagus nerve (tenth cranial nerve).
A non-neoplastic or neoplastic disorder affecting the accessory nerve (eleventh cranial nerve).
A non-neoplastic or neoplastic disorder affecting the hypoglossal nerve (twelfth cranial nerve).
Disorder characterized by discrete episodes of loss of control of aggressive impulses that may result in serious assault or destruction of property.
An area of depressed vision located at the point of fixation and that interferes with central vision.
A type of astigmatism in which the principle meridians are not 90 degrees apart and which is associated with loss of vision. []
Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, eccentric fixation, and reduced or complete loss of color discrimination. All individuals with achromatopsia (achromats) have impaired color discrimination along all three axes of color vision corresponding to the three cone classes: the protan or long-wavelength-sensitive cone axis (red), the deutan or middle-wavelength-sensitive cone axis (green), and the tritan or short-wavelength-sensitive cone axis (blue). Most individuals have complete achromatopsia, with total lack of function of all three types of cones. Rarely, individuals have incomplete achromatopsia, in which one or more cone types may be partially functioning. The manifestations are similar to those of individuals with complete achromatopsia, but generally less severe. Hyperopia is common in achromatopsia. Nystagmus develops during the first few weeks after birth followed by increased sensitivity to bright light. Best visual acuity varies with severity of the disease; it is 20/200 or less in complete achromatopsia and may be as high as 20/80 in incomplete achromatopsia. Visual acuity is usually stable over time; both nystagmus and sensitivity to bright light may improve slightly. Although the fundus is usually normal, macular changes (which may show early signs of progression) and vessel narrowing may be present in some affected individuals. Defects in the macula are visible on optical coherence tomography.
Strabismus in which the angle of deviation of the squiting eye remains the same in rleation to the other eye, in all directions of gaze, and whichever eye is fixing.
Esotropia in which either eye may be used for fixation.
A type of exotropia in which either eye may be used for fixation. [ORCID:0000-0003-0986-4123]
A form of manifest strabismus (heterotropia) in which one eye is deviated downwards when both eyes are open. [ORCID:0000-0003-0986-4123]
A form of manifest strabismus (heterotropia) in which the one eye is wheel rotated so that the upper end of its vertical axis is nasal (incyclotropia) or temporal (excyclotropia). [ORCID:0000-0003-0986-4123]
A form of strabismus with both eyes turned inward to a relatively mild degree, usually defined as less than 10 prism diopters.
A form of strabismus with one or both eyes deviated outward to a milder degree than with exotropia.
A form of latent strabismus (heterophoria) in which the occluded eye wheel-rotates on dissociation. [ORCID:0000-0003-0986-4123]
A type of vertical phoria in which, in dissociation, the occluded eye deviates upwards. [ORCID:0000-0003-0986-4123]
An ocular deviation caused by a palsy to one or more of the extraocular muscles or nerves supplying them. [ORCID:0000-0003-0986-4123]
A rare syndrome affecting conjugate vertical eye movement. It is often caused by a dorsal midbrain neoplasm, commonly a pinealoma, but may also be attributable to demyelinating diseases or stroke. Clinical signs include limitation of upward gaze, light-near dissociation of the pupillary response, eyelid retraction (Collier's sign) and convergence-retraction nystagmus. Clinical course is dependent on effective treatment of underlying cause.
Abnormally increased lacrimation, that is, excessive tearing (watering eye).
A congenital abnormality in which the margins of the upper and lower eyelids are fused together by bands of tissue.
A rare neural tube defect characterized by extreme retroflexion of the head and severe defects of the spine. It is usually associated with other congenital anomalies.
Outward turning of the heel, resulting in clubfoot with the person walking on the inner part of the foot.
Progressive acquired flatfoot in which the arch of the foot is flat only when standing. It is often caused by POSTERIOR TIBIAL TENDON DYSFUNCTION.
A congenital anatomic anomaly in which the heart has only two chambers.
A malformation of the uterus in which the uterus is present as a paired organ as a result of the failure of fusion of the mullerian ducts during embryogenesis.
A locally aggressive and destructive benign cystic lesion of the bone. It is characterized by the formation of multiloculated hemorrhagic cystic spaces which are separated by fibrous septa. It can arise from any bone, but usually affects the metaphysis of long bones. It manifests with pain and swelling and may recur following curettage.
A separation of the iris from the ciliary body.
Adhesions between the iris and the cornea.
Adhesions between the iris and the lens.
A morphologic finding indicating intracytoplasmic fat accumulation in the liver parenchyma.
A pinguecula is a yellowish to brown protruding lesion in the conjunctiva that is easily seen on the nasal and temporal sides of the cornea. [PMID:24311926]
a form of osteoporosis due to immobilization or inactivity.
A reactive inflammatory disorder affecting the bladder. It is characterized by the development of small cysts in the bladder wall. The cysts are lined by urothelial cells.
Polycythemia that occurs in groups of related individuals.
A subtype of classical Hodgkin lymphoma with scattered Reed-Sternberg and Hodgkin cells in a diffuse or vaguely nodular mixed inflammatory background without nodular sclerosing fibrosis. (WHO, 2008)
A diffuse subtype of classical Hodgkin lymphoma which is rich in Hodgkin and Reed-Sternberg cells and/or depleted in non-neoplastic lymphocytes. (WHO, 2008)
A subtype of classical Hodgkin lymphoma characterized by collagen bands that surround at least one nodule, and Hodgkin and Reed-Sternberg cells with lacunar type morphology. (WHO, 2008)
A tumor mass composed of myeloblasts or immature myeloid cells. It occurs in extramedullary sites or the bone. (WHO, 2001)
A developmental abnormality in which the bottom of the tongue is attached to the floor of the mouth.
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective). [pmid:19152421]
The absence of the lens of the eye that is present at the time of birth.
An umbrella term used to describe several very different complex congenital heart defects that share the same problem: the heart has only one functional ventricle (anatomically right or left or indeterminate) supplying the systemic circulation. These defects include tricuspid atresia, hypoplastic left or right heart syndrome, double outlet right ventricle, double inlet left ventricle, and other forms of single ventricle defects.
A neural tube defect in which both the brain and spinal cord remain open to varying degrees.
A congenital abnormality characterized by more than 5 digits on a hand or foot.
A congenital disorder where the hymen (a membrane that surrounds or partially covers the external vaginal opening) does not have an opening and completely obstructs the vagina.
A polyp in the uterine cavity that is formed by placenta remnants.
A congenital skeletal deformity characterized by the elevation of one scapula (thus, one scapula is located superior to the other).
A vitreoretinal dystrophy characterized by splitting of the neuroretinal layers. It occurs in two forms: degenerative retinoschisis and X chromosome-linked juvenile retinoschisis.
An anomaly related to partial closure, or failure of development of the ulnar side of the distal radial growth plate, which results in an arrest of epiphyseal growth of the medial and volar portions of the distal radius. This leads to shortening of the radius and relative overgrowth of the ulna.
Dilatation of the lumen of the mammary ducts without evidence of epithelial atypia.
A pouch or sac-like protrusion from the urethra.
Abnormal widening of the central spinal canal.
A chronic, persistent inflammation of the glomeruli, which is slowly progressive, leading to impaired kidney function.
A partial or complete adhesion of the palpebral conjunctiva of the eyelid to the bulbar conjunctiva of the eyeball.
dryness with ulceration and perforation of the cornea, with absence of inflammatory reactions, occurring in cachectic children; results from severe vitamin A deficiency.
Grey-green or brownish-pigmented ring in the deep epithelial layers at the outer border of the cornea.
An abnormal white reflection from the pupil rather than the usual black reflection.
A chronic and progressive inflammatory process that affects the glans penis and the foreskin. It presents with white atrophic patches in the glans of penis and foreskin and it is often associated with the development of a sclerotic, whitish ring in the tip of the foreskin that may lead to phimosis. It is also known as lichen sclerosus of the penis.
Osteomyelitis caused by infection with the bacteria, salmonella.
Gastroenteritis resulting from a viral infection.
Bronchiectasis that develops in patients with a history of pulmonary tuberculosis. It is usually associated with healed scars but occasionally may be seen in patients with active pulmonary tuberculosis.
Inflammation of brain tissue caused by infection with the varicella-zoster virus (HERPESVIRUS 3, HUMAN). This condition is associated with immunocompromised states, including the ACQUIRED IMMUNODEFICIENCY SYNDROME. Pathologically, the virus tends to induce a vasculopathy and infect oligodendrocytes and ependymal cells, leading to CEREBRAL INFARCTION, multifocal regions of demyelination, and periventricular necrosis. Manifestations of varicella encephalitis usually occur 5-7 days after onset of HERPES ZOSTER and include HEADACHE; VOMITING; lethargy; focal neurologic deficits; FEVER; and COMA. (From Joynt, Clinical Neurology, 1996, Ch 26, pp29-32; Hum Pathol 1996 Sep;27(9):927-38)
A painful blister of the periungual skin that is caused by herpes simplex virus type 1 or 2.
A form of arboviral encephalitis (which primarily affects horses) endemic to western and central regions of NORTH AMERICA. The causative organism (ENCEPHALOMYELITIS VIRUS, WESTERN EQUINE) may be transferred to humans via the bite of mosquitoes (CULEX tarsalis and others). Clinical manifestations include headache and influenza-like symptoms followed by alterations in mentation, SEIZURES, and COMA. DEATH occurs in a minority of cases. Survivors may recover fully or be left with residual neurologic dysfunction, including PARKINSONISM, POSTENCEPHALITIC. (From Joynt, Clinical Neurology, 1996, Ch26, pp8-9)
A form of arboviral encephalitis (primarily affecting equines) endemic to eastern regions of North America. The causative organism (ENCEPHALOMYELITIS VIRUS, EASTERN EQUINE) may be transmitted to humans via the bite of AEDES mosquitoes. Clinical manifestations include the acute onset of fever, HEADACHE, altered mentation, and SEIZURES followed by coma. The condition is fatal in up to 50% of cases. Recovery may be marked by residual neurologic deficits and EPILEPSY. (From Joynt, Clinical Neurology, 1996, Ch26, pp9-10)
A group of viral illnesses that are vectored by mosquitoes, and that are characterized by increased susceptibility to bleeding diatheses.
A stage of syphilis that occurs fifteen to thirty years after the initial infection; it can include gumma formation and cardiovascular or central nervous system involvement (neurosyphilis).
A fungal infection by any of the Candida species in two or more non-contiguous sterile body compartments.
Infection of the prostate gland caused by Trichomonas vaginalis.
A primary or metastatic malignant neoplasm involving the lip.
A malignant neoplasm affecting the tongue. The vast majority of cases are carcinomas.
A primary or metastatic malignant neoplasm that affects the base of the tongue.
A malignant neoplasm that arises from the submandibular gland. The majority are carcinomas.
A rare malignant neoplasm that arises from the sublingual gland. The majority are carcinomas.
A primary or metastatic malignant neoplasm that affects the gums.
A primary or metastatic malignant neoplasm that affects the floor of the mouth. The majority of cases are carcinomas.
A primary or metastatic malignant neoplasm involving the buccal mucosa.
A primary or metastatic malignant neoplasm that affects the hard palate.
A primary or metastatic malignant neoplasm that affects the soft palate.
A primary or metastatic malignant neoplasm that affects the uvula.
A primary or metastatic malignant neoplasm that affects the hard palate, soft palate, or uvula.
A primary or metastatic malignant neoplasm involving the oral cavity. The majority are squamous cell carcinomas.
A primary or metastatic malignant neoplasm that affects the oropharynx.
A primary or metastatic malignant neoplasm involving the nasopharynx.
A primary or metastatic malignant neoplasm that affects the hypopharynx.
A primary or metastatic malignant neoplasm that affects the pyriform sinus.
A primary or metastatic malignant neoplasm that affects the pharynx.
A primary or metastatic malignant neoplasm involving the thoracic region of the esophagus.
A primary or metastatic malignant neoplasm involving the upper third segment of the esophagus.
A primary or metastatic malignant neoplasm involving the middle third segment of the esophagus.
A primary or metastatic malignant neoplasm involving the lower third segment of the esophagus.
A primary or metastatic malignant neoplasm involving the small intestine.
A primary or metastatic malignant neoplasm that affects the duodenum. Representative examples include carcinoma, lymphoma, and sarcoma.
A primary or metastatic malignant neoplasm that affects the cecum. Representative examples include carcinoma, lymphoma, and sarcoma.
A primary or metastatic malignant neoplasm that affects the rectosigmoid area. Representative examples include carcinoma, lymphoma, and sarcoma.
A primary or metastatic malignant neoplasm that affects the anal canal or perianal skin. Representative examples include carcinomas, lymphomas, and melanomas.
A primary or metastatic malignant neoplasm that affects the gallbladder. Representative examples include carcinoma, lymphoma, melanoma, and sarcoma.
A primary or metastatic malignant neoplasm that affects the extrahepatic bile ducts. Representative examples include carcinoma and sarcoma.
A primary or metastatic malignant neoplasm involving the ampulla of Vater.
A primary or metastatic malignant neoplasm involving the retroperitoneum. The vast majority of cases are carcinomas, lymphomas, or sarcomas.
A primary or metastatic malignant neoplasm involving the peritoneum. Representative examples include carcinoma and malignant mesothelioma.
A malignant neoplasm affecting the spleen. Representative examples include leukemias, lymphomas, and sarcomas.
A primary or metastatic malignant neoplasm involving the paranasal sinuses.
A primary or metastatic malignant neoplasm involving the maxillary sinus.
A primary or metastatic malignant neoplasm involving the ethmoid sinus.
A primary or metastatic malignant neoplasm involving the frontal sinus.
A primary or metastatic malignant neoplasm involving the sphenoid sinus.
A malignant neoplasm that affects the glottic area of the larynx. The vast majority of cases represent squamous cell carcinomas.
A malignant neoplasm that affects the supraglottic area of the larynx. The vast majority of cases are squamous cell carcinomas.
A malignant neoplasm that affects the subglottic area of the larynx. The vast majority of cases are squamous cell carcinomas.
A primary or metastatic malignant neoplasm involving the trachea.
A primary or metastatic malignant neoplasm affecting the pleura. A representative example of primary malignant pleural neoplasm is the malignant pleural mesothelioma. A representative example of metastatic malignant neoplasm to the pleura is metastatic carcinoma that has spread to the pleura from another anatomic site.
A primary or metastatic malignant neoplasm involving the heart.
A primary or metastatic malignant neoplasm affecting the mediastinum. Representative examples of primary malignant mediastinal neoplasms include malignant germ cell tumors, malignant mesenchymal tumors, lymphomas, and malignant peripheral nerve sheath tumors. A representative example of metastatic malignant neoplasm to the mediastinum is the metastatic carcinoma to the mediastinum from another anatomic site.
A primary or metastatic malignant neoplasm that affects the mandible.
A Kaposi sarcoma arising from the skin. It presents with patches, plaques, or nodules.
A Kaposi sarcoma arising from the palate.
Primary or metastatic malignant neoplasm involving the uterine corpus and/or the cervix.
A malignant neoplasm that affects the endocervix.
A malignant neoplasm that affects the exocervix.
A primary or metastatic neoplasm that affects the placenta.
A malignant neoplasm that affects the uterine corpus. Representative examples include endometrial carcinoma, carcinosarcoma, leiomyosarcoma, and adenosarcoma.
A primary or metastatic malignant neoplasm that affects the fallopian tube. Representative examples include carcinoma, carcinosarcoma, and leiomyosarcoma.
A malignant neoplasm that affects the clitoris.
Testicular germ cell tumors (TGCTs) affect 1 in 500 men and are the most common cancer in males aged 15 to 40 in western European populations. The incidence of TGCT rose dramatically during the 20th century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT, and a family history of the disease. Brothers of men with TGCT have an 8- to 10-fold risk of developing TGCT, whereas the relative risk to fathers and sons is 4-fold. This familial relative risk is much higher than that for most other types of cancer (summary by Rapley et al., 2000). Genetic Heterogeneity of Testicular Germ Cell Tumors A locus for testicular germ cell tumors (TGCT1; 300228) has been identified on chromosome Xq27.
A primary or metastatic malignant neoplasm that affects the penis. Representative examples include penile carcinoma and penile sarcoma.
A primary or metastatic malignant neoplasm that affects the epididymis. Representative examples include primary epididymal adenocarcinoma and metastatic carcinoma to the epididymis arising from another anatomic site.
A primary or metastatic malignant neoplasm that affects the spermatic cord.
A primary or metastatic malignant neoplasm affecting the scrotum.
A primary or metastatic malignant neoplasm involving the male reproductive system. Representative examples include prostate carcinoma, penile carcinoma, testicular seminoma, and testicular embryonal carcinoma.
The opening of the ureter in the bladder that is situated at the lateral angle of the trigone.
A primary or metastatic malignant neoplasm that affects the renal pelvis.
A primary or metastatic malignant tumor involving the ureter. The majority are carcinomas. -- 2003
Abnormal malignant growth of cells in the urethra (lower urinary tract).
A primary or metastatic malignant neoplasm involving the orbit.
Primary or metastatic malignant neoplasm affecting the lacrimal gland.
A malignant growth of cells within the conjunctiva of the eye.
A malignant growth of cells within the cornea of the eye.
A primary or metastatic malignant neoplasm that affects the choroid.
A primary or metastatic malignant neoplasm affecting the lacrimal duct.
A primary or metastatic malignant neoplasm affecting the brain.
Primary and secondary (metastatic) malignant tumors that occur in the cerebellum. Histologic types include medulloblastomas, high grade (WHO Stage III or IV) cerebellar astrocytomas, lymphomas, gangliogliomas, gliosarcomas, and several other subtypes. The most frequent malignant cerebellar neoplasm of childhood is medulloblastoma. In adults, metastases from other sites are relatively common. Clinical features include ataxia, headache, nausea, dizzyness, nystagmus, diplopia, papilledema, etc.
A primary or metastatic malignant neoplasm that affects the brain stem.
Abnormal malignant growth of the cells that comprise the cranial nerve.
A primary or metastatic malignant neoplasm affecting the spinal cord. Representative examples include lymphoma, melanoma, and sarcoma.
A primary or metastatic malignant neoplasm affecting the parathyroid glands.
Abnormal malignant growth of the cells that comprise the pineal parenchyma.
A carotid body paraganglioma that metastasizes to other anatomic sites.
A malignant neoplasm affecting the endocrine glands. Representative examples include thyroid gland carcinoma, parathyroid gland carcinoma, pituitary gland carcinoma, and adrenal cortex carcinoma.
A primary or metastatic malignant neoplasm affecting the tissues of the thorax.
The spread of a malignant neoplasm to the lung. This may be from a primary lung malignant neoplasm, or from a malignant neoplasm at a distant site.
The spread of a malignant neoplasm to the mediastinum from an adjacent or distant anatomic site.
The spread of a malignant neoplasm to the pleura from an adjacent or distant anatomic site.
The spread of a malignant neoplasm to the kidney. This may be from a primary kidney malignant neoplasm involving the opposite kidney, or from a malignant neoplasm at a distant site.
The spread of a malignant neoplasm to the skin. This may be from a primary skin malignant neoplasm, or from a malignant neoplasm at a distant site.
The spread of a malignant neoplasm from a primary site to the skeletal system. The majority of metastatic neoplasms to the bone are carcinomas.
An antiquated term that refers to a non-Hodgkin lymphoma composed of diffuse infiltrates of large, often anaplastic lymphocytes affecting the spleen.
An antiquated term that refers to a non-Hodgkin lymphoma composed of small and medium sized lymphocytes affecting the spleen.
An obsolete term that refers to Hodgkin lymphoma with splenic involvement.
Ann Arbor Classification: Stage III: Involvement of lymph node regions on both sides of the diaphragm (III), which also may be accompanied by extralymphatic extension in association with adjacent lymph node involvement (IIIE) or by involvement of the spleen (IIIS) or both (IIIE,S). - 2003
Ann Arbor Classification: Stage II: Involvement of two or more lymph node regions on the inferior side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph node(s) with or without involvement of other lymph node regions on the same side of the diaphragm (IIE). Note: The number of lymph node regions involved may be indicated by a subscript.
Stage I Hodgkin lymphoma involving the subdiaphragmatic region.
A rare Hodgkin lymphoma that arises from the spleen.
History of plasmacytic leukemia after therapy with no evidence on the peripheral blood or bone marrow of leukemia (normalization of all hematologic parameters).
Acute lymphoblastic leukemia not growing; responding to treatment.
Chronic lymphocytic leukemia not growing, responding to treatment.
Acute myeloid leukemia not growing, responding to treatment.
Chronic myeloid leukemia not growing; responding to treatment.
A myeloid sarcoma that is responding to therapy, i.e. is not progressing and possibly regressing. --2003
An acute monocytic leukemia responding to treatment and not proliferating.
A non-metastasizing neoplasm that arises from the lip.
A non-metastasizing neoplasm that arises from the tongue.
A non-metastasizing neoplasm that arises from the floor of the mouth.
A non-metastasizing neoplasm that arises from the tonsil.
A non-metastasizing neoplasm that arises from the nasopharynx. Nasopharyngeal angiofibroma is a representative example.
A non-metastasizing neoplasm that arises from the hypopharynx.
A non-metastasizing neoplasm arising from the pharynx. Representative examples include squamous papilloma and nasopharyngeal angiofibroma.
A non-metastasizing neoplasm arising from the esophageal wall.
A non-metastasizing neoplasm arising from the gastric wall.
A non-metastasizing neoplasm arising from the wall of the small intestine.
A non-metastasizing neoplasm that arises from the larynx. Representative examples include squamous papilloma and hemangioma.
A non-metastasizing neoplasm that arises from the trachea.
A non-metastasizing neoplasm that arises from the pleura. Representative examples include lipoma and adenomatoid tumor.
A non-metastasizing neoplasm that arises from the mediastinum. Representative examples include lipoma, leiomyoma, and schwannoma.
A non-metastasizing neoplasm that arises from the heart. Representative examples include atrial myxoma, cardiac lipoma, and cardiac fibroma.
A benign adipose tissue neoplasm of the spermatic cord. This is the most common tumor amongst the benign paratesticular lesions.
A non-metastasizing neoplasm that arises from the cervix. Representative examples include squamous papilloma, endocervical polyp, and rhabdomyoma.
A non-metastasizing neoplasm that arises from the uterine corpus. Representative examples include leiomyoma, adenomyoma, endometrial stromal nodule, and endometrial polyp.
A non-metastasizing neoplasm that arises from the uterine corpus or the cervix. Representative examples include leiomyoma, adenomyoma, and endocervical polyp.
A non-metastasizing neoplasm that arises from the vagina. Representative examples include squamous papilloma and melanocytic nevus.
A non-metastasizing neoplasm that arises from the vulva. Representative examples include cellular angiofibroma, melanocytic nevus, nodular hidradenoma, and Bartholin gland adenoma.
A non-metastasizing neoplasm that arises from the testis. Representative examples include benign Sertoli cell tumor, thecoma, and fibroma.
A non-metastasizing neoplasm that arises from the prostate. Representative examples include benign phyllodes tumor, leiomyoma, and fibroma.
A rare non-metastasizing neoplasm that arises from the epididymis. Representative examples include adenomatoid tumor and leiomyoma.
A non-metastasizing neoplasm that arises from the scrotum.
A non-metastasizing neoplasm that arises from the renal pelvis. Urothelial papilloma is a representative example.
Abnormal growth of the cells of the ureter (upper urinary tract) without malignant characteristics.
A benign abnormal growth of the cells that comprise the bladder.
Abnormal growth of the cells of the urethra (lower urinary tract) without malignant characteristics.
A non-metastasizing neoplasm that arises from the orbit.
Abnormal growth of the cells of the lacrimal gland without malignant characteristics.
Abnormal growth of the cells of the conjunctiva without malignant characteristics.
Abnormal growth of the cells of the cornea without malignant characteristics.
Abnormal growth of the cells of the retina without malignant characteristics.
A non-metastasizing neoplasm that arises from the choroid.
Abnormal growth of the cells of the lacrimal duct without malignant characteristics.
A primary, non-invasive neoplasm without metastatic potential affecting the spinal cord. Representative examples include dermoid cyst, lipoma, and neurofibroma.
A benign neoplasm arising from the thyroid gland.
A non-metastasizing neoplasm arising from the adrenal gland. (NCI05)
A benign neoplasm arising from the parathyroid glands.
A benign growth of the cells that comprise the pineal gland. Despite benign histology, symptoms can be produced due to the location: increased intracranial pressure, endocrine abnormalities, cerebellar and/or brainstem compression. The latter can produce a constellation of symptoms known as Parinaud's syndrome.
A hemangioma arising from the brain and meninges.
A hemangioma arising from organs within the abdominal cavity.
A non-metastasizing neoplasm that arises in a lymph node.
A carcinoma that arises from the tracheal mucosa and is confined to the epithelial layer without evidence of further tissue invasion.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No clinical or radiographic evidence of distant metastasis. (AJCC 6th and 7th eds.)
A condition in which abnormal cells have not spread outside the duct, lobule, or nipple to other tissues of the breast. There are 3 types of breast carcinoma in situ: DUCTAL CARCINOMA IN SITU; LOBULAR CARCINOMA IN SITU; and PAGET DISEASE OF THE NIPPLE
High grade prostatic intraepithelial neoplasia characterized by the presence of severe architectural and cytologic abnormalities.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. cN0: No palpable or visibly enlarged inguinal lymph nodes. pN0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
A neoplasm displaying morphologic, phenotypic, or genotypic characteristics that are clearly not benign but do not permit the establishment of a definitive diagnosis of malignancy. Such neoplasms may or may not eventually have a more aggressive clinical course. Representative examples include lymphoproliferations of uncertain malignant potential (e.g., lymphomatoid granulomatosis and lymphomatoid papulosis), borderline ovarian epithelial neoplasms (e.g., borderline ovarian endometrioid tumor and borderline ovarian mucinous tumor), borderline exocrine pancreatic neoplasm (e.g., pancreatic borderline intraductal papillary-mucinous neoplasm), and primary borderline peritoneal epithelial neoplasm.
An inflammatory disorder of unknown etiology that affects the thyroid gland. It is characterized by extensive fibrosis of the thyroid parenchyma. The fibrosis extends beyond the thyroid gland capsule to the adjacent structures.
A non-neoplastic or neoplastic disorder that affects the thymus. Representative examples include thymic hyperplasia, thymoma, and thymic carcinoma.
A genetic inborn error of metabolism characterized by the deficiency of one of the enzymes necessary for the urea cycle. It results in accumulation of ammonia in the body.
An inherited metabolic disorder caused by an enzyme deficiency, resulting in an inability to oxidize fatty acids for energy production.
A laboratory test result indicating abnormally high proliferation of gamma globulins in the blood originating from multiple cell lines.
A rare dysgammaglobulinemia characterized by low or undetectable serum levels of immunoglobulin class M (IgM). It is an uncommon primary antibody deficiency. It is most likely an inherited immunodeficiency. It may be caused by decreased or inefficient production of IgM from progenitor B cells without any corresponding decreases in the other isotypes. There is a widely variable clinical course. Some affected individuals may be asymptomatic while others show increased susceptibility to infection, malignancy and autoimmune disorders.
Inflammation of the lymph nodes that is chronic in nature.
A dysfunction in biological function that is due to a psychological process.
Physical symptoms or physiological abnormalities that have a psychological origin, and which are usually mediated through the autonomic nervous systems and do not involve tissue damage.
A skin disorder for which mental factors play a causative role.
A dysfunction in genitourinary function that is due to a psychological process.
An endocrine disorder that is caused by abnormal mental function.
An eating disorder most commonly observed in infants characterized by the repeated regurgitation and rechewing of food for a period of at least one month; this behavior is not associated with a gastrointestinal or other medical reason.
Temporary but prolonged and maladaptive depressive signs and symptoms associated with a life event.
Meningitis in which eosinophils predominate in the cerebrospinal fluid.
result of genetic metabolic defects or damage by exogenous or endogenous toxins; characterized by cerebral cortex atrophy and progressive cerebral demyelination; dementia and mental deterioration are common.
A focal dystonia of the fingers, hand, and/or forearm that appears when the affected person attempts to do a task that requires fine motor movements such as writing or playing a musical instrument.
A progressive neurodegenerative disorder affecting upper motor neurons, characterized by progressive muscle weakness.
A type of spastic cerebral palsy characterized by increased muscle tone of the arm and leg on the same side of the body.
A migraine disorder characterized by episodes that are preceded by focal neurological symptoms.
A fluid filled sac within the cerebrum. It is can be congenital, trauma related or secondary to another medical condition for example an infarction.
Disease involving the ULNAR NERVE from its origin in the BRACHIAL PLEXUS to its termination in the hand. Clinical manifestations may include PARESIS or PARALYSIS of wrist flexion, finger flexion, thumb adduction, finger abduction, and finger adduction. Sensation over the medial palm, fifth finger, and ulnar aspect of the ring finger may also be impaired. Common sites of injury include the AXILLA, cubital tunnel at the ELBOW, and Guyon's canal at the wrist. (From Joynt, Clinical Neurology, 1995, Ch51 pp43-5)
A granulomatous, inflammatory disorder of the eye; reaction to vegetable or insect hairs.
Excessive axial myopia associated with complications (especially posterior staphyloma and CHOROIDAL NEOVASCULARIZATION) that can lead to BLINDNESS.
A type of retinal detachment arising from damage to the outer blood-retinal barrier that allows fluid to access the subretinal space and separate the neurosensory retina from the retinal pigment epithelium.
An imperfection of the retina of the eye.
A type of retinal detachment arising due to a combination of contracting retinal membranes, abnormal vitreoretinal adhesions, and vitreous changes. It is usually seen in the context of diseases that induce a fibrovascular response, e.g. diabetes.
Advanced retinopathy due to diabetes mellitus characterized by the formation of new vessels in the retina. The new vessels are abnormal and fragile. If hemorrhage occurs due to the vascular fragility, there is increased risk of vision loss or blindness.
NDP-related retinopathies are characterized by a spectrum of fibrous and vascular changes of the retina at birth that progress through childhood or adolescence to cause varying degrees of visual impairment. The most severe phenotype is described as Norrie disease (ND), characterized by grayish-yellow fibrovascular masses (pseudogliomas) secondary to retinal vascular dysgenesis and detachment. Congenital blindness is almost always present. Approximately 30%-50% of males with ND have developmental delay/intellectual disability, behavioral abnormalities, or psychotic-like features. The majority of males with ND develop sensorineural hearing loss. Less severe phenotypes include: persistent hyperplastic primary vitreous (PHPV), characterized by a fibrotic white stalk from the optic disk to the lens; X-linked familial exudative vitreoretinopathy (XL-FEVR), characterized by peripheral retinal vascular anomalies with or without fibrotic changes and retinal detachment; retinopathy of prematurity (ROP); and Coats disease, an exudative proliferative vasculopathy. Phenotypes can vary within families.
Retinal damage resulting from diminished blood flow/oxygenation due to abnormalities of the retinal vessels. Causes include hypertension, diabetes, thrombosis, embolism, and hemorrhage.
Dilatation of small blood vessels of the retina.
A partial occlusion of the retinal artery.
A partial, temporary occlusion of the retinal artery.
A form of macular degeneration characterized by the presence of multiple cysts in the macula.
Formation of new blood vessels on the iris. The new vessels do not display the typical radially symmertic growth pattern of normal iris blood vessels, but rather appear disorganized. Rubeosis usually starts from the pupillary border with tiny tufts of dilated capillaries or red spots that can only be appreciated with high magnification.
An abnormal reduction in the amount of pigmentation of the iris.
Presenile cataract is a kind of cataract that occurs in early adulthood, that is, at an age that is younger than usual.
Normal color vision in humans is trichromatic, being based on 3 classes of cone that are maximally sensitive to light at approximately 420 nm (blue cones; 613522), 530 nm (green cones; 300821), and 560 nm (red cones; 300822). Comparison by neural circuits of light absorption by the 3 classes of cone photoreceptors allows perception of red, yellow, green, and blue colors individually or in various combinations. Dichromatic color vision is severely defective color vision based on the use of only 2 types of photoreceptors, blue plus green (protanopia) or blue plus red (deuteranopia; see 303800). Anomalous trichromacy is trichromatic color vision based on a blue, green, and an anomalous red-like photoreceptor (protanomaly), or a blue, red, and an anomalous green-like photoreceptor (deuteranomaly). The color vision defect is generally mild but may in certain cases be severe. Common variation in red-green color vision exists among both normal and color-deficient individuals (review by Deeb, 2005).
A type of anomalous trichromacy associated with abnormal M photopigment, such that the absorption spectrum is shifted toward L wavelengths. Affected individuals have difficulties distinguishing between red and green.
Tritanopia is an autosomal dominant disorder of human vision characterized by a selective deficiency of blue spectral sensitivity (Weitz et al., 1992).
Injury to the cornea secondary to ultraviolet light.
Reduced transparency of the peripheral region of the cornea.
Keratopathy that is characterized by the presence of epithelial bullae.
Presence of folds in the Descement membrane, which is the basement membrane of the endothelial (inner) cell layer of the cornea. Descement membrane folds are generally a manifestation of inflammation or edema of the cornea.
The presence of recurrent corneal epithelial erosions. Although most corneal epithelial defects heal quickly, some may show recurrent ulcerations.
An abnormality of the cornea characterized by the deposition of calcium in a band across the central cornea, leading to decreased vision, foreign body sensation, and ocular irritation.
The presence of fine, branching linear opacities in Bowman's layer in the central area that may spread to the periphery in the clinical course. The deep corneal stroma may be involved but the process does not reach Descemet's membrane. Recurrent corneal erosion may occur. Histologic examination reveals amyloid deposits in the collagen fibers of the cornea.
Conjunctivitis that is characterized by formation of a pseudomembrane.
Conjunctivitis that is persistent and long-standing.
A granuloma located on the conjunctiva, usually involving the inner surface of the eyelid.
Abnormal fluid filled sac within the conjunctiva.
An abnormal inversion of the eyelid towards the globe resulting from inferior retractor muscle dysfunction with tissue laxity and, possibly, overriding of the preseptal orbicularis muscle over the pretarsal orbicularis muscle. [ORCID:0000-0003-0986-4123]
A type of entropion (abnormal inversion of the eyelid towards the globe) that is related to a mass effect of a lesion (e.g., a tumor) that pulls the eyelid margin away from the globe. [ORCID:0000-0003-0986-4123]
Abnormal inversion (turning inward) of the eyelid towards the globe associated with scarring that vertically shortens the posterior lamella of the eyelid. [ORCID:0000-0003-0986-4123]
An outward turning (eversion) or rotation of the eyelid margin (i.e., ectropion) caused by shortening or contraction of the anterior or middle lamellae related to scarring. [ORCID:0000-0003-0986-4123]
A type of lagophthalmos that occurs in association with facial nerve palsy.
A type of lagophthalmos that occurs following trauma or surgery.
A condition characterized by the formation of fatty deposits under the skin in the area of the eyelids. These well-demarcated growths, more common in women than men and sometimes hereditary, may indicate elevated cholesterol levels in the blood or the fatty degeneration of the superficial fibers of the orbicularis muscle.
Localized swelling of the eyelid due to blockage of the meibomian glands, usually caused by inflammation.
Any non-neoplastic or neoplastic disorder affecting the arteries, veins, or lymphatic vessels of the eyelid.
Inflammation and enlargement of the lacrimal gland.
A congenital or acquired mucocele that develops in the lacrimal sac. It is usually the result of nasolacrimal duct abnormalities or obstruction.
Punctal stenosis is a condition in which the external opening of the lacrimal canaliculus is narrowed or occluded. [PMID:22848141]
A granuloma located on the orbit of the eye.
Presence of a cyst in the region of the periorbital tissues. Orbital cysts can be derived from epithelial or glandular tissue within or surrounding the orbit (lacrimal glands, salivary glands, conjunctival, oral, nasal, or sinus epithelium).
A disorder of the neural pathway from the optic nerve to the visual cortex.
A cleft of the optic nerve that extends inferiorly.
Apparent optic disc swelling in the absence of increased intracranial pressure.
Ischemic injury to the OPTIC NERVE which usually affects the OPTIC DISK (optic neuropathy, anterior ischemic) and less frequently the retrobulbar portion of the nerve (optic neuropathy, posterior ischemic). The injury results from occlusion of arterial blood supply which may result from TEMPORAL ARTERITIS; ATHEROSCLEROSIS; COLLAGEN DISEASES; EMBOLISM; DIABETES MELLITUS; and other conditions. The disease primarily occurs in the sixth decade or later and presents with the sudden onset of painless and usually severe monocular visual loss. Anterior ischemic optic neuropathy also features optic disk edema with microhemorrhages. The optic disk appears normal in posterior ischemic optic neuropathy. (Glaser, Neuro-Ophthalmology, 2nd ed, p135)
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.
A form of esotropia (convergent deviation of the eyes) associated with activation of the accommodative reflex. [ORCID:0000-0003-0986-4123]
Paralysis of both the extrinsic and intrinsic ocular muscles.
Brown syndrome, originally described by Brown (1950), is characterized by the inability to elevate the adducted eye actively or passively. There is less elevation deficit with the eye in midposition, and minimal or no deficit in abduction. There can also be divergence on upgaze, downshoot, or widening of the palpebral fissure on adduction, primary hypotropia, and anomalous head posture. Brown syndrome accounts for approximately 2% of strabismus cases. Ten percent of cases are bilateral, and left- and right-sided unilateral cases are equal in frequency. There is no gender predilection (summary by Heidary et al., 2012).
A staphyloma is a localized defect in the eye wall with protrusion of uveal tissue due to alterations in scleral thickness and structure.
A localized defect in the posterior eye wall with protrusion of uveal tissue due to alterations in scleral thickness and structure.
Any disease affecting the vitreous body of the eye.
Nystagmus due to disturbance of the vestibular system; eye movements are rhythmic, with slow and fast components.
A non-neoplastic or neoplastic disorder that affects the pinna and/or the ear canal. Representative examples include infection and carcinoma.
A benign bony growth projecting outward from a bone surface within the external auditory canal.
A mass of KERATIN-producing squamous EPITHELIUM that resembles an inverted (suck-in) bag of skin in the MIDDLE EAR. It arises from the eardrum (TYMPANIC MEMBRANE) and grows into the MIDDLE EAR causing erosion of EAR OSSICLES and MASTOID that contains the INNER EAR.
As accumulation of granulation tissue in the middle ear that results from the degeneration of blood and a chronic inflammatory response.
Benign recurrent vertigo (BRV), also known as benign paroxysmal positional vertigo (BPPV), is a common disorder affecting up to 2% of the adult population. The majority of individuals with chronic recurrent vertigo have no identifiable cause, no progression of the disorder, and no other neurologic or auditory signs. Many families have multiple affected individuals, suggesting familial transmission of the disorder with moderate to high penetrance (summary by Lee et al., 2006).
Altered sense of hearing, other than simple decreased hearing or deafness
Discharge or drainage of fluid from the ear.
A type of hearing loss resulting from a combination of conductive hearing impairment and sensorineural hearing impairment.
Inflammation of the pericardium in acute rheumatic heart disease.
Inflammation of the endocardium in acute rheumatic heart disease.
Inflammation of the myocardium in acute rheumatic heart disease.
A condition of mild to moderate high blood pressure that has no identifiable cause.
High blood pressure caused by an underlying medical condition.
Mild to moderate high blood pressure that is caused by an underlying medical condition.
High blood pressure caused by renal artery stenosis.
Necrosis of the myocardium, as a result of interruption of the blood supply to the area. It is characterized by a severe and rapid onset of symptoms that may include chest pain, often radiating to the left arm and left side of the neck, dyspnea, sweating, and palpitations.
Documented history of previous myocardial infarction (MI), typically with objective evidence via positive biomarkers of myocardial necrosis.
A congenital or acquired malformation characterized by abnormal communication between the pulmonary arteries and pulmonary veins in the lungs.
An aneurysm (severe localized balloon-like outward bulging) in the pulmonary artery.
The sudden onset of inflammation of heart muscle with myocellular necrosis; this is generally secondary to an infectious cause, and patients often have a recent history of a flu-like illness.
A disorder characterized by an electrocardiographic finding of intermittent failure of atrial electrical impulse conduction to the ventricles, characterized by a relatively constant PR interval prior to the block of an atrial impulse. (CDISC)
Abnormal conduction in all three divisions of the intraventricular conducting tissue.
The presence of atheromas or atherosclerotic plaques in the aorta.
An atherosclerotic lesion located in the renal artery. []
Sudden breakage of an artery leading to leakage of blood from the circulation.
The formation of a blood clot (thrombus) in the portal vein.
An abnormally dilated superficial vein in the legs.
Varicosity of veins in the vulval region.
Recurrent nasal polyps with subsequent destruction of the nasal pyramid.
Persistent laryngitis usually caused by smoking, heavy alcohol consumption, voice abuse, or gastroesophageal reflux disease. It results in hoarseness and other voice changes.
An abscess that develops in the soft tissues of the lateral pharyngeal space.
An abscess that develops in the soft tissues behind the posterior pharyngeal wall.
A febrile disease caused by STREPTOCOCCUS PNEUMONIAE.
Asthma is a breathing disorder characterized by inflammation of the airways and recurrent episodes of breathing difficulty. These episodes, sometimes referred to as asthma attacks, are triggered by irritation of the inflamed airways. In allergic asthma, the attacks occur when substances known as allergens are inhaled, causing an allergic reaction. Allergens are harmless substances that the body's immune system mistakenly reacts to as though they are harmful. Common allergens include pollen, dust, animal dander, and mold. The immune response leads to the symptoms of asthma. Allergic asthma is the most common form of the disorder.A hallmark of asthma is bronchial hyperresponsiveness, which means the airways are especially sensitive to irritants and respond excessively. Because of this hyperresponsiveness, attacks can be triggered by irritants other than allergens, such as physical activity, respiratory infections, or exposure to tobacco smoke, in people with allergic asthma.An asthma attack is characterized by tightening of the muscles around the airways (bronchoconstriction), which narrows the airway and makes breathing difficult. Additionally, the immune reaction can lead to swelling of the airways and overproduction of mucus. During an attack, an affected individual can experience chest tightness, wheezing, shortness of breath, and coughing. Over time, the muscles around the airways can become enlarged (hypertrophied), further narrowing the airways.Some people with allergic asthma have another allergic disorder, such as hay fever (allergic rhinitis) or food allergies. Asthma is sometimes part of a series of allergic disorders, referred to as the atopic march. Development of these conditions typically follows a pattern, beginning with eczema (atopic dermatitis), followed by food allergies, then hay fever, and finally asthma. However, not all individuals with asthma have progressed through the atopic march, and not all individuals with one allergic disease will develop others.
Chronic airway obstruction caused by asthma.
Pulmonary alveolar microlithiasis is a rare disease characterized by the deposition of calcium phosphate microliths throughout the lungs. Most patients are asymptomatic for several years or even for decades, and, generally, the diagnosis is incidental to clinical investigations unrelated to the specific disorder. Cases with early onset or rapid progression are rare. A 'sandstorm-appearing' chest roentgenogram is a typical diagnostic finding. The onset of this potentially lethal disease varies from the neonatal period to old age, and the disease follows a long-term progressive course, resulting in a slow deterioration of lung functions. About one-third of the reported cases are said to be familial (summary by Corut et al., 2006).
Secondary retention is the cessation of eruption of a tooth after emergence that does not result from a physical barrier in the path of eruption or an abnormal position of the tooth. Permanent molars are less frequently affected than deciduous molars. The major characteristic of a secondarily retained molar is infraocclusion, which may result in malocclusion because of tilting of the neighboring teeth and overeruption of antagonists. The disorder can also result in loss of the retained molar and neighboring teeth due to caries and periodontal disease and in deformation of the facial skeleton (Raghoebar et al., 1992). See also 125350 and 273050 for phenotypes with shared features of secondary retention of permanent molars.
Glossy appearance of the entire tongue surface.
Inflammation of the stomach resulting from alcohol ingestion.
A protrusion of necrotic tissue through the abdominal wall under the skin near the umbilicus.
Crohn's disease affecting the small intestine.
Blockage of the normal flow of the contents of the gallbladder.
An abnormal communication between the gallbladder and another organ or cavity.
A rupture in the wall of the extrahepatic or intrahepatic bile duct due to traumatic or pathologic processes.
An acute inflammation of the glomeruli, generally secondary to infection or injury.
A renal functional disorder characterized by proteinuria, edema, hyperlipidemia and hypoalbuminemia. It results from damage to the renal vascular filtration apparatus. It is further characterized by an inflammatory reaction of the glomerular capillaries due to the proliferation of mesangial cells and expansion of the mesangial matrix. Sequelae may include hypertension, atherosclerosis, infection, hypercoagulablity and renal failure.
A renal functional disorder characterized by proteinuria, edema, hyperlipidemia and hypoalbuminemia. It results from damage to the renal vascular filtration apparatus. It is further characterized by an inflammatory reaction in the glomerular capillaries due to the deposition of immune complexes and subsequent thickening of the glomerular basement membrane. Sequelae may include hypertension, atherosclerosis, infection, hypercoagulablity and renal failure.
A renal functional disorder characterized by proteinuria, edema, hyperlipidemia and hypoalbuminemia. It results from damage to the renal vascular filtration apparatus. It is further characterized by an inflammatory reaction of the glomerular capillaries due to the proliferation of mesangial cells, expansion of the mesangial matrix and deposition of immune complexes causing subsequent thickening of the glomerular basement membrane. Sequelae may include hypertension, atherosclerosis, infection, hypercoagulablity and renal failure.
A slowly progressive inflammation of the glomeruli occurring status post infection with streptococcus.
Global enlargement of the renal parenchyma in one or both kidneys.
Inflammation of the bladder due to irradiation.
An abnormal communication between the urinary bladder and the intestine.
Diverticulum (sac or pouch) in the wall of the urinary bladder.
Rupture in the bladder wall due to a pathologic process, in the absence of trauma.
A non-neoplastic or neoplastic disorder that affects the blood vessels of the penis. Representative examples include atherosclerosis, venous leak, and hemangioma.
Breast fibrocystic change characterized by the prominence of fibrotic changes in the parenchyma.
Localized necrosis of the adipose tissue in the breast. Clinically, it may present as a mass. Causes include injury, surgical procedures, and radiation treatment.
A non-neoplastic disorder characterized by the growth of endometrial tissue in the ovaries. It results in the development of blood filled ovarian cysts (chocolate cysts), and creation of scars and adhesions.
A benign protruding lesion arising either from the endometrial cavity (endometrial polyp) or the endocervix (endocervical polyp). It may occasionally recur following complete resection.
A condition with obliterated endometrial cavity causing secondary AMENORRHEA.
A benign polypoid lesion arising from the vaginal wall.
Deviations from the normal process; e.g. delayed, difficult, profuse, scanty, unusual bleeding, etc.
Non-menstrual bleeding that occurs during or after sexual intercourse.
The unintentional or intentional loss of a pregnancy before 22 weeks gestation.
High blood pressure in the period of time preceding labor and delivery.
High blood pressure in the period of time immediately after labor and delivery.
More than or equal to 6 cm dilation with membrane rupture and one of the following: 4 hours or more of adequate contractions (e.g. more than 200 Montevideo units), 6 hours or more of inadequate contractions and no cervical change.
At least 2 hours of pushing in multiparous women and at least 3 hours of pushing in nulliparous women. Longer durations may be appropriate on an individualized basis (e.g., with the use of epidural analgesia or with fetal malposition) as long as progress is being documented.
Renal failure that occurs postpartum due to any partum problem (hemorrhage, sepsis, preeclampsia).
Dermatitis caused by an allergic reaction to an unspecified ingested substance.
Autosomal dominant vibratory urticaria is characterized by localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum (Boyden et al., 2016).
A disorder of joint(s) caused by the presence of an infectious agent in the joint(s).
Arthropathy resulting from Behcet's syndrome.
Juvenile rheumatoid arthritis affecting four or fewer joints, usually asymmetrically. The most commonly affected joints are the knee, elbow, wrist, and ankle.
Arthritis occurring after the ingestion of allergenic substance(s).
Dislocation of joint caused by presence of another disease
Contractures of one ore more joints of the hands meaning chronic loss of joint motion due to structural changes in non-bony tissue.
Lumbar disc disease is caused by degeneration of intervertebral discs of the lumbar spine. One of the most common musculoskeletal disorders, it has strong genetic determinants (Matsui et al., 1998; Battie et al., 1995; Sambrook et al., 1999).
Any disease of a degenerative nature that affects the intervertebral disc.
An abnormal narrowing of the lumbar spinal canal.
A bony outgrowth on the lower surface of the CALCANEUS. Though often presenting along with plantar fasciitis (FASCIITIS, PLANTAR), they are not considered causally related.
A painful disability in the hand affecting the finger or thumb. It is caused by mechanical impingement of the digital flexor tendons as they pass through a narrowed retinacular pulley at the level of the metacarpal head. Thickening of the sheath and fibrocartilaginous metaplasia can occur, and nodules can form. (From Green's Operative Hand Surgery, 5th ed, p2137-58).
Narrowing or stenosis of a tendon's retinacular sheath. It occurs most often in the hand or wrist but can also be found in the foot or ankle. The most common types are DE QUERVAIN DISEASE and TRIGGER FINGER DISORDER.
An infectious process affecting the skeletal muscles. It can be caused by viruses (including HIV), bacteria, fungi, and parasites. Symptoms include muscle weakness and muscle pain.
A fibromatosis of the plantar fascia characterized by thickening of the fibrous bands on the plantar aponeurosis in the sole of the foot and toes.
A form of myositis that is characterized by the formation of connective tissue within the muscle.
Aseptic necrosis involving the head of the humerus.
Union of the fragments of a fractured bone in a faulty or abnormal position. If two bones parallel to one another unite by osseous tissue, the result is a crossunion. (From Manual of Orthopaedic Terminology, 4th ed)
A type of congenital cataract in which the opacities are confined to a small central area within the embryonic or fetal nuclei of the Iens. The remaining lens is clear. [HPO:probinson]
A spectrum of congenital, inherited, or acquired abnormalities in BLOOD VESSELS that can adversely affect the normal blood flow in ARTERIES or VEINS. Most are congenital defects such as abnormal communications between blood vessels (fistula), shunting of arterial blood directly into veins bypassing the CAPILLARIES (arteriovenous malformations), formation of large dilated blood blood-filled vessels (cavernous angioma), and swollen capillaries (capillary telangiectases). In rare cases, vascular malformations can result from trauma or diseases.
Dysfunction of the aortic valve characterized by incomplete valve closure that is present at birth.
Any structural abnormality of the coronary arteries.
A congenital heart disorder in which one or two pulmonary veins are not connected to the left atrium and drain into the right atrium instead. It may lead to arrhythmias and pulmonary hypertension.
A malformation in the lung that is present at birth. Representative examples include pulmonary hypoplasia, pulmonary agenesis, congenital lobar emphysema, and alveolar capillary dysplasia.
Cleft lip and cleft palate are birth defects that occur when a baby's lip or mouth do not form properly. They happen early during pregnancy. A baby can have a cleft lip, a cleft palate, or both. A cleft lip happens if the tissue that makes up the lip does not join completely before birth. This causes an opening in the upper lip. The opening can be a small slit or a large opening that goes through the lip into the nose. It can be on one or both sides of the lip or, rarely, in the middle of the lip. Children with a cleft lip also can have a cleft palate. The roof of the mouth is called the palate. With a cleft palate, the tissue that makes up the roof of the mouth does not join correctly. Babies may have both the front and back parts of the palate open, or they may have only one part open. Children with a cleft lip or a cleft palate often have problems with feeding and talking. They also might have ear infections, hearing loss, and problems with their teeth. Often, surgery can close the lip and palate. Cleft lip surgery is usually done before age 12 months, and cleft palate surgery is done before 18 months. Many children have other complications. They may need additional surgeries, dental and orthodontic care, and speech therapy as they get older. With treatment, most children with clefts do well and lead a healthy life. Centers for Disease Control and Prevention.
Absence of the tongue owing to a developmental abnormality.
Autosomal dominant aplasia of lacrimal and salivary glands is a rare condition characterized by irritable eyes, epiphora (constant tearing), and xerostomia (dryness of the mouth), which increases risk of dental erosion, dental caries, periodontal disease, and oral infections. ALSG has variable expressivity, and affected individuals may have aplasia or hypoplasia of the lacrimal, parotid, submandibular, and sublingual glands and absence of the lacrimal puncta. In affected individuals, the misdiagnosis is often made of the more prevalent disorder Sjogren syndrome (270150), an autoimmune condition characterized by keratoconjunctivitis sicca and xerostomia. Both sporadic and familial cases of ALSG have been described (summary by Entesarian et al., 2005).
A usually asymptomatic hereditary disorder which is often associated with polycystic kidney disease. It is characterized by the presence of fluid-filled biliary cysts throughout the liver.
An abnormality of the kidney, ureter, bladder, or urethra that is present at birth. Representative examples include renal hypoplasia, renal agenesis, accessory kidney, absence of ureter, atresia of bladder neck, and atresia of urethra.
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
A kind of polydactyly characterized by the presence of a supernumerary finger or fingers.
A kind of polydactyly characterized by the presence of a supernumerary toe or toes.
Webbing or fusion of the fingers, involving soft parts and including fusion of individual finger bones. Bony fusions are referred to as ""bony"" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers in a proximo-distal axis are referred to as ""Symphalangism"".
Webbing or fusion of the toes, involving soft parts and including fusion of individual bones of the toes. Bony fusions are referred to as ""bony"" Syndactyly if the fusion occurs in a tibial-fibular axis. Fusions of bones of the toes in a proximo-distal axis are referred to as ""Symphalangism"".
An abnormal osseous union (fusion) between the radius and the ulna.
An abnormality of one or more of the vertebrae.
A developmental defect characterized by agenesis of one or more vetebral bodies.
A supernumerary rib developing from an abnormal enlargement of the costal element of the C7 vertebra. This anomaly is found in 1-2% of the population and can put pressure on adjacent structures causing CERVICAL RIB SYNDROME; THORACIC OUTLET SYNDROME; or other conditions.
A newborn infant who has a weight at birth greater than 4500 grams.
A respiratory disorder characterized by higher than normal respiratory rates among premature and cesarean section delivered neonates whose lungs have not fully matured. The cause is often excess fluid in the lungs, and resolution is aided by supplemental oxygen and sometimes, antibiotics.
An infection with the Cytomegalovirus that is present from birth.
Loss of blood from the fetal circulation.
Hyperglycemia in the newborn due to a defect in the secretion or function of insulin.
A disorder of neuromuscular transmission that occurs in a minority of newborns born to women with myasthenia gravis. Clinical features are usually present at birth or develop in the first 3 days of life and consist of hypotonia and impaired respiratory, suck, and swallowing abilities. This condition is associated with the passive transfer of acetylcholine receptor antibodies through the placenta. In the majority of infants the myasthenic weakness resolves (i.e., transient neonatal myasthenia gravis) although this disorder may rarely continue beyond the neonatal period (i.e., persistent neonatal myasthenia gravis). (From Menkes, Textbook of Child Neurology, 5th ed, p823; Neurology 1997 Jan;48(1):50-4)
A hypermetabolic syndrome characterized by tachycardia, palpitations, tremor, weight loss, and moist skin that is caused by the elevation of thyroid hormone levels in the serum of the newborn infant or thyroid-axis receptor activation, most commonly due to transplacental passage of thyroid stimulating globulins.
Blood glucose concentration below the lower limit of established reference ranges in a newborn.
A clotting condition characterized as a disruption in the homeostatic balance of the coagulation and fibrinolytic systems presenting as a pathological activation of coagulation mechanisms leading to the formation of small clots inside the blood vessels throughout the body of the newborn.
Anemia, the cause of which is present at birth.
A blood disorder characterized by low hemoglobin levels in premature neonates that usually spontaneously resolves within 3-6 months post birth. A combination of factors including the transition from the liver to the bone marrow for erythropoiesis in a neonate, blood loss experienced during delivery, the shortened life span of fetal blood cells, and an acclimation to a relatively hyperoxic environment outside the womb can predispose a neonate to this condition.
Abnormal hypersynchronous electrical activity in the brain of a newborn which may be associated with stereotyped movements or autonomic changes.
An anomaly of the amount or nature of abdominal sounds. Abdominal sounds (bowel sounds) are made by the movement of the intestines as they promote passage of abdominal contents by peristalsis.
The clinical electro-oculogram (EOG) is an electrophysiological test of function of the outer retina and retinal pigment epithelium (RPE) in which changes in electrical potential across the RPE are recorded during successive periods of dark and light adaptation.
Late radiation injury (LRI) is the damage to the soft tissue and bone following radiation therapy that occurs weeks and years after the radiation exposure. Pathogenesis of LRI stems from ischemia, interruption of the blood supply and direct cell damage. LRIs include but not limited to the skin atrophy, ulceration and non-healing wounds; cystitis, proctosigmoiditis, resulting to fistulas, abscesses, fibrosis and scaring; laryngitis, osteoradionecrosis; central nervous system injury, optic neuropathy.
A disease or disorder that is associated with a transplanted lung.
A disease or disorder that is associated with a transplanted pancreas.
Any heart or vascular disorder occurring as a consequence of injury to the cardiovascular system.
Any disorder of the organs of the digestive system occurring as a consequence of injury to the digestive system.
Any disorder of the organs of the urinary system occurring as a consequence of injury to the urinary system.
A non-neoplastic proliferation of a nerve caused by injury to the nerve due to trauma or surgery. It presents as a firm nodule that may be associated with pain or tenderness. It most often occurs in the lower extremity following amputation, or in the head and neck region.
A reduction in erythrocytes volume or hemoglobin concentration.
Scars that form a depression compared to the level of the surrounding skin because of damage to the collagen, fat or other tissues below the skin.
High levels of ketone bodies in the urine.
Nephrogenic diabetes insipidus (NDI) is characterized by inability to concentrate the urine, which results in polyuria (excessive urine production) and polydipsia (excessive thirst). Affected untreated infants usually have poor feeding and failure to thrive, and rapid onset of severe dehydration with illness, hot environment, or the withholding of water. Short stature and secondary dilatation of the ureters and bladder from the high urine volume is common in untreated individuals.
Paralysis of the external ocular muscles.
A sensation of discomfort and tightness while moving a joint. Typically there is decreased joint range of motion. Causes include arthritis, joint overuse, joint injury, and the aging process.
Abnormal fluid filled sac within the thyroid gland.
X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and the adrenal cortex. Three main phenotypes are seen in affected males: The childhood cerebral form manifests most commonly between ages four and eight years. It initially resembles attention-deficit disorder or hyperactivity; progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms and often lead to total disability within six months to two years. Most individuals have impaired adrenocortical function at the time that neurologic disturbances are first noted. Adrenomyeloneuropathy (AMN) manifests most commonly in an individual in his twenties or middle age as progressive stiffness and weakness of the legs, sphincter disturbances, sexual dysfunction, and often, impaired adrenocortical function; all symptoms are progressive over decades. ""Addison disease only"" presents with primary adrenocortical insufficiency between age two years and adulthood and most commonly by age 7.5 years, without evidence of neurologic abnormality; however, some degree of neurologic disability (most commonly AMN) usually develops by middle age. More than 20% of female carriers develop mild-to-moderate spastic paraparesis in middle age or later. Adrenal function is usually normal.
Anemia caused by low iron intake, inefficient iron absorption in the gastrointestinal tract, or chronic blood loss.
An arthritis affecting five or more separate joints.
A hypersensitivity condition of skin or mucous membranes at the site of direct surface contact with irritants or allergens. A general class that includes both immunologic and non-immunologic conditions.
A nitrogen-free bisphosphonate analog of naturally occurring pyrophosphate. Clodronate disodium binds to calcium and inhibits osteoclastic bone resorption and hydroxyapatite crystal formation and dissolution, resulting in a reduction of bone turnover. This agent may control malignancy-associated hypercalcemia, inhibit osteolytic bone metastasis and decrease pain. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41862&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41862&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1418"" NCI Thesaurus)
Hypohidrotic ectodermal dysplasia (HED) is characterized by hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat), and hypodontia (congenital absence of teeth). The cardinal features of classic HED become obvious during childhood. The scalp hair is thin, lightly pigmented, and slow-growing. Sweating, although present, is greatly deficient, leading to episodes of hyperthermia until the affected individual or family acquires experience with environmental modifications to control temperature. Only a few abnormally formed teeth erupt, and at a later-than-average age. Physical growth and psychomotor development are otherwise within normal limits. Mild HED is characterized by mild manifestations of any or all the characteristic features.
Hidrotic ectodermal dysplasia 2, or Clouston syndrome (referred to as HED2 throughout this GeneReview) is characterized by partial or total alopecia, dystrophy of the nails, hyperpigmentation of the skin (especially over the joints), and clubbing of the fingers. Sparse scalp hair and dysplastic nails are seen early in life. In infancy, scalp hair is wiry, brittle, patchy, and pale; progressive hair loss may lead to total alopecia by puberty. The nails may be milky white in early childhood; they gradually become dystrophic, thick, and distally separated from the nail bed. Palmoplantar keratoderma may develop during childhood and increases in severity with age. The clinical manifestations are highly variable even within the same family.
An imbalanced nutritional status resulting from insufficient intake of nutrients to meet normal physiological requirement.
A variant of parapsoriasis in which the plaques are large.
A complication of OBSTETRIC LABOR in which the corpus of the UTERUS is forced completely or partially through the UTERINE CERVIX. This can occur during the late stages of labor and is associated with IMMEDIATE POSTPARTUM HEMORRHAGE.
The co-occurrence of pregnancy and parasitic diseases. The parasitic infection may precede or follow FERTILIZATION.
Painful red or pink edematous nodules most commonly found on the palmar and/or plantar regions.
A rare congenital disorder characterised by multifocal, segmental dilatation of the large intrahepatic bile ducts. It may present at any age and predominantly affects females. Less than 250 cases have been described worldwide. Caroli disease is characterised by bile ductal ectasia without other apparent hepatic abnormalities. It presents with recurrent bacterial cholangitis, biliary stones causing biliary pain or episodes of pancreatitis. The more common variant of this disease, named Caroli syndrome, is characterised by dilatations of the large bile duct associated with congenital hepatic fibrosis. The aetiology of Caroli disease is unknown and its occurrence is sporadic, whereas Caroli syndrome is generally inherited in an autosomal recessive manner.
Opportunistic infections found in patients who test positive for human immunodeficiency virus (HIV). The most common include PNEUMOCYSTIS PNEUMONIA, Kaposi's sarcoma, cryptosporidiosis, herpes simplex, toxoplasmosis, cryptococcosis, and infections with Mycobacterium avium complex, Microsporidium, and Cytomegalovirus.
Ankyrin Repeats are tandem modules of about 33 amino acids. The conserved domain structure has been described as side-by-side anti-parallel alpha helices connected by intervening beta hairpin motifs or as beta, alpha, alpha, beta secondary structures or as an L-shaped beta-hairpin and two alpha-helices. The repeats associate to form a higher order structure. Despite sequence variation, the domain core maintains a stable surface of contact residues to mediate protein-protein interactions. Target protein binding involves contacts by the beta hairpin tips and the helical bundle surface facing the Ankyrin groove. ANK repeats have been identified in over 1700 functionally diverse proteins, primarily from eukaryotes; no common theme among the protein targets has been identified. The Ankyrin cytoskeletal protein is composed almost entirely of these repeats.
Inflammation of the COLON due to colonic ISCHEMIA resulting from alterations in systemic circulation or local vasculature.
Congenital erythropoietic porphyria (CEP) is characterized in most individuals by severe cutaneous photosensitivity with blistering and increased friability of the skin over light-exposed areas. Onset in most affected individuals occurs at birth or early infancy. The first manifestation is often pink to dark red discoloration of the urine. Hemolytic anemia is common and can range from mild to severe, with some affected individuals requiring chronic blood transfusions. Porphyrin deposition may lead to corneal ulcers and scarring, reddish-brown discoloration of the teeth (erythrodontia), and mild bone loss and/or expansion of the bone marrow. The phenotypic spectrum, however, is broad and ranges from non-immune hydrops fetalis in utero to late-onset disease with only mild cutaneous manifestations in adulthood.
Hereditary coproporphyria (HCP) is an acute (hepatic) porphyria in which the acute symptoms are neurovisceral and occur in discrete episodes. Attacks typically start in the abdomen with low-grade pain that slowly increases over a period of days (not hours) with nausea progressing to vomiting. In some individuals, the pain is predominantly in the back or extremities. When an acute attack is untreated, a motor neuropathy may develop over a period of days or a few weeks. The neuropathy first appears as weakness proximally in the arms and legs, then progresses distally to involve the hands and feet. Some individuals experience respiratory insufficiency due to loss of innervation of the diaphragm and muscles of respiration. Acute attacks are associated commonly with use of certain medications, caloric deprivation, and changes in female reproductive hormones. About 20% of those with an acute attack also experience photosensitivity associated with bullae and skin fragility.
Variegate porphyria (VP) is a cutaneous porphyria (with chronic blistering skin lesions) and an acute porphyria (with severe episodic neurovisceral symptoms). The most common manifestation of VP is adult-onset cutaneous blistering lesions (subepidermal vesicles, bullae, and erosions that crust over and heal slowly) of sun-exposed skin, especially the hands and face. Other chronic skin findings include milia, scarring, thickening, and areas of decreased and increased skin pigmentation. Facial hyperpigmentation and hypertrichosis may occur. Cutaneous manifestations may improve in winter, and be less prevalent in northern regions and in dark-skinned individuals. Acute neurovisceral symptoms can occur any time after puberty, but less often in the elderly. Acute manifestations are highly variable, but may be similar from episode to episode in a patient with recurrent attacks; not all symptoms are present in a single episode; and acute symptoms may become chronic. Symptoms are more common in women than men. The most common symptoms are abdominal pain; constipation; pain in the back, chest, and extremities; anxiety; seizures; and a primarily motor neuropathy resulting in muscle weakness that may progress to quadriparesis and respiratory paralysis. Psychiatric disturbances and autonomic neuropathy can also be observed. Acute attacks may be severe and are potentially fatal.
A group of metabolic diseases due to deficiency of one of a number of LIVER enzymes in the biosynthetic pathway of HEME. They are characterized by the accumulation and increased excretion of PORPHYRINS or its precursors. Clinical features include neurological symptoms (PORPHYRIA, ACUTE INTERMITTENT), cutaneous lesions due to photosensitivity (PORPHYRIA CUTANEA TARDA), or both (HEREDITARY COPROPORPHYRIA). Hepatic porphyrias can be hereditary or acquired as a result of toxicity to the hepatic tissues.
Decreased levels of immunoglobulin IgA. [HPO:probinson]
An abnormally decreased level of immunoglobulin G (IgG) in blood.
A condition associated with the use of certain medications and characterized by an internal sense of motor restlessness often described as an inability to resist the urge to move.
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.
Acute intermittent porphyria (referred to as AIP in this GeneReview) results from half-normal activity of the enzyme hydroxymethylbilane synthase (HMBS). It is characterized clinically by life-threatening acute neurovisceral attacks of severe abdominal pain without peritoneal signs, often accompanied by nausea, vomiting, tachycardia, and hypertension. Attacks may be complicated by neurologic findings (mental changes, convulsions, and peripheral neuropathy that may progress to respiratory paralysis), and hyponatremia. Acute attacks, which may be provoked by certain drugs, alcoholic beverages, endocrine factors, calorie restriction, stress, and infections, usually resolve within two weeks. Most individuals with AIP have one or a few attacks; about 5% (mainly women) have recurrent attacks (defined as >4 attacks/year) that may persist for years. Other long-term complications are chronic renal failure, hepatocellular carcinoma (HCC), and hypertension. Attacks, which are very rare before puberty, are more common in women than men. All individuals with a genetic change in the gene HMBS that predisposes to AIP are at risk of developing acute attacks; however, most never have symptoms and are said to have latent (or presymptomatic) AIP.
A cutaneous form of the genetic photosensitive disease, porphyria, that is characterized by onset in adult life and the presence of scarring bullae, hyperpigmentation, facial hypertrichosis, and sometimes sclerodermatous thickenings and alopecia. Uroporphyrins are found in the urine due to a deficiency of uroporphyrinogen decarboxylase, an enzyme required for the synthesis of heme.
A rare congenital metabolic disorder characterized by an inborn error of porphyrin-heme biosynthesis. It is caused by deficiency of the enzyme ferrochelatase. Signs and symptoms include painful cutaneous photosensitivity leading to blistering and scarring of the exposed skin areas, erythrodontia, red discoloration of urine, hemolytic anemia, and splenomegaly.
Hepatoerythropoietic porphyria (HEP) is characterized by blistering skin lesions, hypertrichosis, and scarring over the affected skin areas. Disease manifestations occur during infancy or childhood and with similar frequency in females and males. Individuals with HEP are not reported to be at increased risk for hepatocellular carcinoma.
An infection that is caused by nematodes of the genus Anisakis, which is most commonly transmitted via ingestion of infective larvae from consumption of raw or undercooked fish or squid; it is characterized by invasion of the stomach wall or intestines, resulting in the death of the worm, and triggering an inflammatory response that surrounds the worm and that can result in intestinal obstruction.
Tumors, cancer or other neoplasms caused by or resulting from trauma or other non-radiation injuries.
Infections with nematodes of the subclass ADENOPHOREA.
Infections with nematodes of the order ENOPLIDA.
Infections with nematodes of the subclass SECERNENTEA.
Infections with nematodes of the order ASCARIDIDA.
A bacterial infection and inflammation of the skin und subcutaneous tissues.
Infections with nematodes of the order OXYURIDA.
Infections with nematodes of the order RHABDITIDA.
The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Virus shedding is an important means of vertical transmission (INFECTIOUS DISEASE TRANSMISSION, VERTICAL).
Angelman syndrome (AS) is characterized by severe developmental delay or intellectual disability, severe speech impairment, gait ataxia and/or tremulousness of the limbs, and a unique behavior with an inappropriate happy demeanor that includes frequent laughing, smiling, and excitability. Microcephaly and seizures are also common. Developmental delays are first noted at around age six months; however, the unique clinical features of AS do not become manifest until after age one year, and it can take several years before the correct clinical diagnosis is obvious.
Infections with nematodes of the order SPIRURIDA.
Infections with nematodes of the order STRONGYLIDA.
A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series.
Dental decay that occurs on the root portion of a tooth.
The hindering of output from the STOMACH into the SMALL INTESTINE. This obstruction may be of mechanical or functional origin such as EDEMA from PEPTIC ULCER; NEOPLASMS; FOREIGN BODIES; or AGING.
A heterogenous group of disorders characterized by alterations of mitochondrial metabolism that result in muscle and nervous system dysfunction. These are often multisystemic and vary considerably in age at onset (usually in the first or second decade of life), distribution of affected muscles, severity, and course. (From Adams et al., Principles of Neurology, 6th ed, pp984-5)
Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutation of genes encoded by either nuclear DNA or mitochondrial DNA (mtDNA). While some mitochondrial disorders only affect a single organ (e.g., the eye in Leber hereditary optic neuropathy [LHON]), many involve multiple organ systems and often present with prominent neurologic and myopathic features. Mitochondrial disorders may present at any age. Many individuals with a mutation of mtDNA display a cluster of clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). However, considerable clinical variability exists and many individuals do not fit neatly into one particular category, which is well-illustrated by the overlapping spectrum of disease phenotypes (including mitochondrial recessive ataxia syndrome (MIRAS) resulting from mutation of the nuclear gene POLG, which has emerged as a major cause of mitochondrial disease. Common clinical features of mitochondrial disease – whether involving a mitochondrial or nuclear gene – include ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus. Common central nervous system findings are fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. A high incidence of mid- and late pregnancy loss is a common occurrence that often goes unrecognized.
MELAS syndrome, comprising mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, is a genetically heterogeneous mitochondrial disorder with a variable clinical phenotype. The disorder is accompanied by features of central nervous system involvement, including seizures, hemiparesis, hemianopsia, cortical blindness, and episodic vomiting (Pavlakis et al., 1984; Montagna et al., 1988). Other mitochondrial encephalomyopathies include Leigh syndrome (LS; 256000), Kearns-Sayre syndrome (KSS; 530000), MERRF syndrome (545000), and Leber optic atrophy (535000).
A condition that can be caused by mutation(s) in more than one mitochondrial gene. It is characterized by myoclonic epilepsy and ragged-red fibers present on muscle biopsy.
Progressive external ophthalmoplegia is a condition characterized by weakness of the eye muscles. The condition typically appears in adults between ages 18 and 40 and slowly worsens over time. The first sign of progressive external ophthalmoplegia is typically drooping eyelids (ptosis), which can affect one or both eyelids. As ptosis worsens, affected individuals may use the forehead muscles to try to lift the eyelids, or they may lift up their chin in order to see. Another characteristic feature of progressive external ophthalmoplegia is weakness or paralysis of the muscles that move the eye (ophthalmoplegia). Affected individuals have to turn their head to see in different directions, especially as the ophthalmoplegia worsens. People with progressive external ophthalmoplegia may also have general weakness of the muscles used for movement (myopathy), particularly those in the neck, arms, or legs. The weakness may be especially noticeable during exercise (exercise intolerance). Muscle weakness may also cause difficulty swallowing (dysphagia).When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells contain an excess of cell structures called mitochondria and are known as ragged-red fibers.Although muscle weakness is the primary symptom of progressive external ophthalmoplegia, this condition can be accompanied by other signs and symptoms. In these instances, the condition is referred to as progressive external ophthalmoplegia plus (PEO+). Additional signs and symptoms can include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), weakness and loss of sensation in the limbs due to nerve damage (neuropathy), impaired muscle coordination (ataxia), a pattern of movement abnormalities known as parkinsonism, and depression.Progressive external ophthalmoplegia is part of a spectrum of disorders with overlapping signs and symptoms. Similar disorders include ataxia neuropathy spectrum and Kearns-Sayre syndrome. Like progressive external ophthalmoplegia, the other conditions in this spectrum can involve weakness of the eye muscles. However, these conditions have many additional features not shared by most people with progressive external ophthalmoplegia.
Virus diseases caused by CALICIVIRIDAE. They include HEPATITIS E; VESICULAR EXANTHEMA OF SWINE; acute respiratory infections in felines, rabbit hemorrhagic disease, and some cases of gastroenteritis in humans.
A group of disorders characterized by an autosomal dominant pattern of inheritance with high rates of spontaneous mutation and multiple neurofibromas or neurilemmomas. NEUROFIBROMATOSIS 1 (generalized neurofibromatosis) accounts for approximately 95% of cases, although multiple additional subtypes (e.g., NEUROFIBROMATOSIS 2, neurofibromatosis 3, etc.) have been described. (From Neurochirurgie 1998 Nov;44(4):267-72)
A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.
Bacterial, viral, or parasitic diseases transmitted to humans and animals by the bite of infected ticks. The families Ixodidae and Argasidae contain many bloodsucking species that are important pests of man and domestic birds and mammals and probably exceed all other arthropods in the number and variety of disease agents they transmit. Many of the tick-borne diseases are zoonotic.
Amount of stimulation required before the sensation of pain is experienced.
Any pharmaceutical that is administered as an inactive precursor that can be converted to its pharmacologically active form through exposure to ultraviolet radiation or sunlight.
A protease inhibitor that is designed to target the human immunodeficiency virus (HIV) protease while sparing other host cell proteases. HIV protease mediates the cleavage of viral Gag, Gag-Pol and Nef precursor polypeptides into their mature proteins. Inhibition of HIV protease results in production of noninfectious viral particles.
The acetate salt form of sermorelin, a synthetic, amidated 29-amino acid peptide that corresponds to the amino-terminal segment of the naturally occurring human growth hormone-releasing hormone (GHRH). Sermorelin acetate directly stimulates the pituitary gland, resulting in release of growth hormone leading to increased plasma growth hormone, which is responsible for many biological processes and counteracts growth hormone deficiency.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
A syndrome of HEMOLYSIS, elevated liver ENZYMES, and low blood platelets count (THROMBOCYTOPENIA). HELLP syndrome is observed in pregnant women with PRE-ECLAMPSIA or ECLAMPSIA who also exhibit LIVER damage and abnormalities in BLOOD COAGULATION.
Collagenases are enzymes that degrade collagen fibers. These enzymes play an important role in connective tissue metabolism and are produced by specific cells involved in both repair and remodeling processes.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT2 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT2 receptor subtypes.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT3 RECEPTORS.
Any agent that binds to and activates serotonin receptors.
Compounds that specifically inhibit the reuptake of serotonin in the brain.
OBSOLETE. The covalent or non-covalent attachment of a farnesyl group to the carboxy terminus of a protein. [GOC:jl]
OBSOLETE. The covalent or non-covalent attachment of a geranylgeranyl group to the carboxy terminus of a protein. [GOC:jl]
A post-translational modification of proteins by the attachment of an isoprenoid to the C-terminal cysteine residue. The isoprenoids used, farnesyl diphosphate or geranylgeranyl diphosphate, are derived from the same biochemical pathway that produces cholesterol.
Enlargement of the RIGHT VENTRICLE of the heart. This increase in ventricular mass is often attributed to PULMONARY HYPERTENSION and is a contributor to cardiovascular morbidity and mortality.
Deletion of sequences of nucleic acids from the genetic material of an individual.
The citrate salt form of sufentanil, a synthetic congener of fentanyl and related to the phenylpieridines, with analgesic property. Sufentanil citrate binds to and activates the mu-opioid receptor, thereby producing analgesia, respiratory depression, miosis, reduced gastrointestinal motility, and euphoria. In addition, this agent has a more rapid onset of action and shorter duration of action compared to fentanyl.
Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the presence of low circulating concentrations of sex steroids. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome) in approximately 60%. IGD can first become apparent in infancy, adolescence, or adulthood. Infant boys with congenital IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.
A group of disorders characterized by swelling, basophilia, and distortion of collagen bundles in the dermis.
Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.
Any of a variety of eruptive skin disorders characterized by erythema, oozing, vesiculation, and scaling. Etiology is varied.
A group of dermatoses with distinct morphologic features. The primary lesion is most commonly a papule, usually erythematous, with a variable degree of scaling on the surface. Plaques form through the coalescing of primary lesions.
A disorder of the vasculature of the skin.
A contact dermatitis due to allergic sensitization to various substances. These substances subsequently produce inflammatory reactions in the skin of those who have acquired hypersensitivity to them as a result of prior exposure.
A non-allergic contact dermatitis caused by prolonged exposure to irritants and not explained by delayed hypersensitivity mechanisms.
A delayed hypersensitivity involving the reaction between sunlight or other radiant energy source and a chemical substance to which the individual has been previously exposed and sensitized. It manifests as a papulovesicular, eczematous, or exudative dermatitis occurring chiefly on the light-exposed areas of the skin.
A nonimmunologic, chemically induced type of photosensitivity producing a sometimes vesiculating dermatitis. It results in hyperpigmentation and desquamation of the light-exposed areas of the skin.
A darkening of the skin related to an increase in melanin production and deposition.
A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections.
A chronic skin condition involving the inflammation of the apocrine sweat glands, forming pimple-like bumps known as abscesses.
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Porokeratosis palmaris plantaris et disseminata (PPPD) is a subtype in which lesions initially develop on the palms and soles, but later involve other parts of the body, including the trunk and limbs (Wei et al., 2003). For a discussion of genetic heterogeneity of porokeratosis, see 174800.
A clonal proliferation of abnormal keratinocytes characterized by the development of localized or multiple atrophic skin patches surrounded by an annular keratotic ring called cornoid lamella.
The change in structure whereby a polypeptide assumes its functional shape or conformation. This is a process that occurs during either protein biosynthesis or protein reconstitution. Polypeptide chains assume their correct three-dimensional conformation through discrete intermediate (primary, secondary, and tertiary) structures prior to the development final quaternary structure.
Conditions in which there is histological damage to the lower epidermis along with a grouped chronic inflammatory infiltrate in the papillary dermis disturbing the interface between the epidermis and dermis. LICHEN PLANUS is the prototype of all lichenoid eruptions. (From Rook et al., Textbook of Dermatology, 4th ed, p398)
A chronic inflammatory disease characterized by shiny, flat-topped, usually flesh-colored micropapules no larger than the head of a pin. Lesions are localized in the early stages, found chiefly on the lower abdomen, penis, and inner surface of the thighs. Distribution may become generalized as the disease progresses.
A rare skin disorder of unknown etiology that is considered to be a more severe form of pityriasis lichenoides. It is characterized by itchy, burning papular lesions which form open sores with red-brown crusts. Low grade fever, headache, malaise, and arthralgias may occasionally precede or accompany the skin findings.
A rare cutaneous disorder of unknown etiology that can present either as an acute condition, with multiple papular lesions which become vesicular and necrotic (pityriasis lichenoides et varioliformis acuta) or chronic, with small, scaling papules (pityriasis lichenoides chronica).
Mucoid states characterized by the elevated deposition and accumulation of mucin (mucopolysaccharides) in dermal tissue. The fibroblasts are responsible for the production of acid mucopolysaccharides (GLYCOSAMINOGLYCANS) in the ground substance of the connective tissue system. When fibroblasts produce abnormally large quantities of mucopolysaccharides as hyaluronic acid, chondroitin sulfate, or heparin, they accumulate in large amounts in the dermis.
An aneurysm that has burst, resulting in hemorrhage into adjacent tissues.
Abnormal balloon- or sac-like dilatation in the wall of any one of the iliac arteries including the common, the internal, or the external ILIAC ARTERY.
An abnormal localized widening (dilatation) of the abdominal aorta. []
An abnormal balloon- or sac-like dilatation in the wall of the THORACIC AORTA. This proximal descending portion of aorta gives rise to the visceral and the parietal branches above the aortic hiatus at the diaphragm.
A topical antimycotic agent for the treatment of dermatomycoses.
Deacetylated CHITIN, a linear polysaccharide of deacetylated beta-1,4-D-glucosamine. It is used in HYDROGEL and to treat WOUNDS.
The active metabolite of the nitrogen mustard cyclophosphamide with potent antineoplastic and immunosuppressive properties. Perfosfamide alkylates DNA, thereby inhibiting DNA replication and RNA and protein synthesis. (NCI04)
An oxazolidinone with centrally-acting skeletal muscle relaxant properties. Although the exact mechanism through which metaxalone exerts its effect is largely unknown, it might be due to general central nervous system (CNS) depression. Metaxalone has no direct effect on the contractile mechanisms of striated muscle, the motor end plate, or the nerve fiber.
An oily liquid that is extracted from the leaves of EUCALYPTUS trees.
A phytonutrient and plant indole found in cruciferous vegetables including broccoli, Brussels sprouts, cabbage, cauliflower and kale, with potential anti-androgenic and antineoplastic activities. As a dimer of indole-3-carbinol, diindolylmethane (DIM) promotes beneficial estrogen metabolism in both sexes by reducing the levels of 16-hydroxy estrogen metabolites and increasing the formation of 2-hydroxy estrogen metabolites, resulting in increased antioxidant activity. Although this agent induces apoptosis in tumor cells in vitro, the exact mechanism by which DIM exhibits its antineoplastic activity in vivo is unknown.
A naturally-occurring phytochemical belonging to the class of isothiocyanates. As the aglycone metabolite of glucosinolate glucoraphanin (sulforaphane glucosinolate), sulforaphane acts as an antioxidant and potent stimulator of endogenous detoxifying enzymes. This agent displays anticarcinogenic properties due to its ability to induce phase II detoxification enzymes, such as glutathione S-transferase and quinone reductase, thereby providing protection against certain carcinogens and toxic, reactive oxygen species. Broccoli sprouts contain large amounts of sulforaphane, which is also found in other cruciferous vegetables including cabbage and kale. (NCI04)
A uridine derivative and nucleoside analog with pro-apoptotic and chemosensitizing properties. In vitro, bromovinyl-deoxyuridine (BVDU) has been shown to downregulate the multifunctional DNA repair enzyme APEX nuclease 1, resulting in the inhibition of DNA repair and the induction of apoptosis. In addition, this agent may inhibit the expression of STAT3 (signal transducer and activator of transcription 3), which may result in the downregulation of vascular endothelial growth factor (VEGF). BVDU has also been found to inhibit the upregulation of chemoresistance genes (Mdr1 and DHFR) during chemotherapy. Overall, the gene expression changes associated with BVDU treatment result in the decrease or prevention of chemoresistance. In addition, this agent has been shown to enhance the cytolytic activity of NK-92 natural killer cells towards a pancreatic cancer cell line in vitro.
Chromium Piccolinate is a salt of the trace metallic element chromium (Cr), essential in glucose metabolism. Found in vitamins and mineral supplements, Chromium may be necessary for utilization of dietary sugars and carbohydrates by optimizing the effects of insulin. Animal studies suggest that chromium picolinate may be carcinogenic, it enters cells directly and can causes mutations. (NCI04)
A moisturizing skincare formulation used for various skin conditions including dry skin conditions associated with eczema, psoriasis, chapped or chafed skin. (NCI)
Dried tree sap from the MASTIC TREE that is used in TRADITIONAL MEDICINE and chewed as gum.
A piperazine histamine H1 receptor antagonist with primarily antiemetic and antivertigo activities. Buclizine binds to and blocks the histamine H1 receptor, thereby preventing the symptoms that are caused by histamine activity. Buclizine exerts its anti-emetic effect by binding to and blocking the muscarinic and histamine receptors in the vomiting center of the central nervous system (CNS). This may prevent activation of the chemoreceptor trigger zone (CTZ) and may reduce nausea and vomiting.
An orally active aminoglutethimide derivative with potential antineoplastic activity. Rogletimide reversibly inhibits the activity of aromatase, a cytochrome P450 family enzyme found in many tissues and the key enzyme in the oxidative aromatization process of androgens to estrogens. In estrogen-dependent cancers, the inhibition of aromatase by this agent leads to a reduction in the synthesis of estrogen, thereby inhibiting estrogen-mediated signal transduction and consequently reducing tumor cell growth. In addition, rogletimide also inhibits enzymes that catalyzing conversion of cholesterol to corticosteroids.
A long-acting, quinazolinesulfonamide derivative with thiazide-like diuretic activity. Quinethazone acts in a similar manner to that of other typical thiazide diuretics and is no longer commercially available in the United States.
An analogue of consensus interferon which contains an additional methionyl amino acid residue. Consensus interferon (also known as interferon alfacon-1, rCon-IFN, and CIFN) is a genetically engineered synthetic interferon created from the most common amino acid sequences from the naturally occurring alpha interferons. Alpha interferons bind to specific cell-surface receptors, resulting in the transcription and translation of genes whose protein products have antiviral, antiproliferative, anticancer, and immune-modulating effects.
A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.
A synthetic cyclic octapeptide analogue of somatostatin with direct and indirect antitumor effects. Vapreotide binds to somatostatin receptors (SSTR), specifically SSTR-2 and to SSTR-5 with a lesser affinity, in the similar behaviors as other octapeptide somatostatin analogues. Like octreotide, this agent has direct and indirect antitumor effects via inhibiting the release of growth hormone and other peptides that regulate release of insulin, gastrointestinal hormones. Furthermore, vapreotide may also be useful for inducing hemostasis in cases of acute hemorrhage of the upper gastrointestinal tract.
A synthetic acyclic guanine derivative with antiviral activity, mainly used to treat infections from herpes simplex virus (HSV) types 1 and 2. In HSV infected cells, penciclovir is phosphorylated by viral thymidine kinase and subsequently converted by cellular kinases into the active metabolite, penciclovir triphosphate, which competitively inhibits viral HSV polymerase by blocking deoxyguanosine triphosphate substrate binding. As a result, herpes viral DNA synthesis and replication are selectively inhibited.
A synthetic agent with immune response modifying activity. As an immune response modifier (IRM), imiquimod stimulates cytokine production, especially interferon production, and exhibits antitumor activity, particularly against cutaneous cancers. Imiquimod's proapoptotic activity appears to be related to Bcl-2 overexpression in susceptible tumor cells. (NCI04)
A diarylsulfonylurea with potential antineoplastic activity. Sulofenur's antineoplastic mechanism of action is unknown. (NCI04)
A triazolopyrimidine derivative diuretic. Bemitradine has thiazide-like actions and is a renal vasodilator. Due to its non-genotoxic carcinogenicity, clinical development for this agent has stopped.
A platinum-based alkylating agent with antineoplastic activity. Although its pharmacokinetic properties are similar to that of carboplatin, enloplatin appears to be non-cross resistant with other platinum-based agents, such as cisplatin and carboplatin.
A non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Trandolaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Trandolaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
An orally-active benzimidazole derivative with potential antineoplastic activity. As a retinoic acid metabolism blocking agent, liarozole inhibits cytochrome P450-dependent all-trans-retinoic acid (ATRA)-4-hydroxylase, resulting in an increase in endogenous ATRA production, inhibition of cell proliferation, and induction of cell differentiation. This agent also inhibits aromatase, the enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis.
An inhibitor of carbonic anhydrase, a zinc-containing enzyme that catalyzes the rapid conversion of carbon dioxide and water into carbonic acid, protons and bicarbonate ions. Distributed throughout many cells and tissues, various carbonic anhydrases play important roles in mineral and metabolic homeostasis. (NCI04)
A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.
A naphthalene derivative that has specificity for RETINOIC ACID RECEPTORS. It is used as a DERMATOLOGIC AGENT for the treatment of ACNE.
An angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, imidapril is converted by hydrolysis in the liver into its active form imidaprilat. Imidaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Imidaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A third-generation, water-soluble platinum compound with potential antineoplastic activity. Lobaplatin forms highly reactive, charged, platinum complexes that bind to nucleophilic groups such as GC- and AG-rich sites in DNA, inducing intrastrand DNA cross-links. These cross-links will ultimately result in induction of apoptosis and cell growth inhibition. Compared to first and second generation platinum compounds, lobaplatin appears to be more stable, less toxic, have a better therapeutic index and may overcome tumor resistance.
A non-thiol angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Zabiciprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Zabiciprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A nitrocatechol compound with anti-parkinsonian property. Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), which catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure including dihydroxyphenylalanine (DOPA), catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. When administered in conjunction with dopaminergic agents such as L-DOPA, entacapone prevents the metabolism and inactivation of adjunct drugs, thereby increasing the bioavailability of these compounds by facilitating their passage across the blood-brain barrier.
A prodrug inhibitor of hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase. In the body dalvastatin is hydrolyzed to its active beta-hydroxy acid form.
The sodium salt of risedronic acid, a synthetic pyridinyl bisphosphonate. Risedronic acid binds to hydroxyapatite crystals in bone and inhibits osteoclast-dependent bone resorption.
A 39 amino acid peptide and synthetic version of exendin-4, a hormone found in the saliva of the venomous lizard Gila monster, with insulin secretagogue and antihyperglycemic activity. Exenatide is administered subcutaneously and mimics human glucagon-like peptide-1 (GLP-1). Compared to GLP-1, exenatide has a longer half-life of 2.4 hours.
The synthetic benzoate ester of estradiol, a steroid sex hormone vital to the maintenance of fertility and secondary sexual characteristics in females. As the primary, most potent estrogen hormone produced by the ovaries, estradiol binds to and activates specific nuclear receptors. This agent exhibits mild anabolic and metabolic properties, and increases blood coagulability. (NCI04)
A 20 amino acid long synthetic peptide with thrombin-specific anticoagulant properties. Bivalirudin reversibly binds thrombin, free as well as clot bound, at the catalytic site and the anion-binding exosite, thereby preventing the formation and activation of fibrin, factor XIIIa, and other coagulation factors. This drug is primarily used during coronary angioplasty procedures, in combination with aspirin, in patients with unstable angina.
A morpholine derivative that is a selective and potent noradrenaline reuptake inhibitor; it is used in the treatment of DEPRESSIVE DISORDER.
An antimetabolite and a chlorine derivative of the purine nucleoside adenosine, with potential antineoplastic activity. Upon administration, 8-chloro-adenosine is phosphorylated to form 8-chloro-adenosine triphosphate (8-chloro-ATP), which functions as a ribonucleoside analogue and competes with ATP during transcription. Therefore, this agent causes RNA synthesis inhibition, inhibits cellular proliferation, and induces apoptosis.
A recombinant form of endogenous human growth hormone (GH), a polypeptide produced by the anterior lobe of the human pituitary gland. GH exhibits growth-promoting effects and metabolic effects on carbohydrate, fat, protein and bone metabolism. GH stimulates protein synthesis and the uptake of amino acids into cells, and induces lipolysis in adipose tissues. The secretion of GH increases with sexual maturation and then declines steadily.
A depsipeptide originally isolated from the marine mollusk Dolabella auricularia with potential antineoplastic activity. Less potent than the structurally-related compound dolastatin 10, dolastatin 15 binds weakly to tubulin and blocks microtubule assembly, thereby inhibiting mitosis. Dolastatin 15 also induces tumor cell apoptosis through a mechanism involving bcl-2, an oncoprotein that is overexpressed in some cancers. (NCI04)
Vaccines or candidate vaccines used to prevent infection with hepatitis A virus (HEPATOVIRUS).
An oil obtained from Chenopodium ambrosioides plants. Chenopodium oil is considered to be toxic but has been used for its anthelmintic properties.
A benzodiazepine derivative that binds SEROTONIN RECEPTORS; MUSCARINIC RECEPTORS; HISTAMINE H1 RECEPTORS; ADRENERGIC ALPHA-1 RECEPTORS; and DOPAMINE RECEPTORS. It is an antipsychotic agent used in the treatment of SCIZOPHRENIA; BIPOLAR DISORDER; and MAJOR DEPRESSIVE DISORDER; it may also reduce nausea and vomiting in patients undergoing chemotherapy.
A synthetic catecholamine with positive chronotropic and inotropic properties, used in echocardiography and diagnostic coronary angiography. Arbutamine binds to and activates beta-1 adrenergic receptors in the myocardium, thereby increasing heart rate and increasing force of myocardial contraction. By exerting a chronotropic and inotropic effect, arbutamine mimics the cardiac stress caused by exercise that may prevent adequate tissue perfusion and oxygenation, and may provoke myocardial ischemia in patients with coronary artery disease.
A cyclopropylpyrroloindole prodrug analogue and DNA minor groove binding agent, with antineoplastic activity. After hydrolysis, the cyclopropyl group of carzelesin alkylates N3-adenine in a sequence-selective fashion. This results in tumor growth inhibition.
A hydroxamic, non-amino acid derivative angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Idrapril competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Idrapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A semisynthetic derivative of the anthracycline antineoplastic antibiotic doxorubicin. As an antineoplastic agent, morpholinodoxorubicin is more potent than doxorubicin. Similar to doxorubicin, morpholinodoxorubicin intercalates into DNA and causes single- and double-strand breaks in DNA via inhibition of topoisomerase I and II. Unlike doxorubicin, this agent is metabolized in vivo to a DNA-alkylating derivative that forms DNA interstrand cross-links, thereby potentiating its doxorubicin-like cytotoxicity. (NCI04)
A subtype of HLA-DRB beta chains that is associated with the HLA-DR53 serological subtype.
Vaccines or candidate vaccines used to prevent PSEUDORABIES (Aujeszky's disease), a herpesvirus of swine and other animals.
An ester alkaloid derived from Rauwolfia canescens with antihypertensive activity. Deserpidine is a competitive inhibitor of the angiotensin converting enzyme (ACE). By competing with angiotensin I for ACE, deserpidine blocks the conversion of angiotensin I to angiotensin II, which is a potent vasoconstrictor. Reduced level of serum angiotensin II causes a decrease in blood pressure. Deserpidine also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex.
A collective term for diseases of the skin and its appendages and of connective tissue.
Visible efflorescent lesions of the skin caused by acne or resembling acne. (Dorland, 28th ed, p18, 575)
Citrullinemia type I (CTLN1) presents as a clinical spectrum that includes an acute neonatal form (the ""classic"" form), a milder late-onset form (the ""non-classic"" form), a form without symptoms or hyperammonemia, and a form in which women have onset of severe symptoms during pregnancy or post partum. Distinction between the clinical forms is based on clinical findings and is not clear-cut. Infants with the acute neonatal form appear normal at birth. Shortly thereafter, they develop hyperammonemia and become progressively lethargic, feed poorly, often vomit, and may develop signs of increased intracranial pressure (ICP). Without prompt intervention, hyperammonemia and the accumulation of other toxic metabolites (e.g., glutamine) result in increased ICP, increased neuromuscular tone, spasticity, ankle clonus, seizures, loss of consciousness, and death. Children with the severe form who are treated promptly may survive for an indeterminate period of time, but usually with significant neurologic deficits. The late-onset form may be milder than that seen in the acute neonatal form, for unknown reasons. The episodes of hyperammonemia are similar to those seen in the acute neonatal form, but the initial neurologic findings may be more subtle because of the older age of the affected individuals.
A rare, autosomal recessive inherited syndrome characterized by microcephaly, growth retardation, and a small, round, triangular shaped face with a pointed, receding chin, a broad, wide-tipped nose, and wide-set eyes with drooping eyelids.
Pancreatitis is inflammation of the pancreas that progresses from acute (sudden onset; duration <6 months) to recurrent acute (>1 episode of acute pancreatitis) to chronic (duration >6 months). The range of symptoms and disease course vary from person to person. Familial pancreatitis, defined as pancreatitis from any cause that occurs in a family with an incidence that is greater than would be expected by chance alone, can be non-genetic or genetic, the latter including autosomal dominant hereditary pancreatitis and pancreatitis syndromes characterized by pancreatitis or pancreatic insufficiency. The majority of familial pancreatitis appears to have a complex, multigenic, or gene-environmental etiology with a variable number of germline pathogenic variants in genes that affect trypsin regulation, including CASR, CTRC, and CLDN2. Hereditary pancreatitis (HP) is defined as either two or more individuals with pancreatitis in two or more generations of a family (i.e., an autosomal dominant pattern of inheritance) or pancreatitis associated with a germline PRSS1 disease-causing gain-of-function variant. The phenotype of hereditary pancreatitis is increased susceptibility to acute pancreatitis, with complications such as chronic inflammation, fibrosis, and chronic pain in some affected individuals. Heterozygous pathogenic variants in PRSS1 are found in 60%-100% of families with hereditary pancreatitis, and most large families with pancreatitis spanning multiple generations; biallelic pathogenic variants in SPINK1 or biallelic pathogenic variants in CFTR result in autosomal recessive pancreatitis. Syndromes in which pancreatitis is a finding include: Pearson marrow pancreas syndrome, CEL maturity-onset diabetes of the young (CEL-MODY), and Johanson-Blizzard syndrome. Shwachman-Diamond syndrome, an autosomal recessive disorder, includes pancreatic exocrine insufficiency as well as other features. Idiopathic sporadic pancreatitis is a single occurrence of pancreatitis in a family for which no etiology is identified.
Russell-Silver syndrome (RSS) is characterized by intrauterine growth retardation accompanied by postnatal growth deficiency. The birth weight of affected infants is typically two or more SD below the mean, and postnatal growth two or more SD below the mean for length or height. Affected individuals typically have proportionately short stature, normal head circumference, fifth-finger clinodactyly, typical facial features with triangular facies characterized by broad forehead and narrow chin, and limb-length asymmetry that may result from hemihypotrophy with diminished growth of the affected side. Growth velocity is normal in children with RSS. The average adult height of males is 151.2 cm and that of females is 139.9 cm. Evidence exists that children with RSS are at significant risk for developmental delay (both motor and cognitive) and learning disabilities.
Smith-Lemli-Opitz syndrome (SLOS) is a congenital multiple anomaly syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol (7-DHC) reductase. It is characterized by prenatal and postnatal growth retardation, microcephaly, moderate to severe intellectual disability, and multiple major and minor malformations. The malformations include distinctive facial features, cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes. The clinical spectrum is wide and individuals have been described with normal development and only minor malformations.
Sotos syndrome is a disorder characterized by a distinctive facial appearance, overgrowth in childhood, and learning disabilities or delayed development of mental and movement abilities. Characteristic facial features include a long, narrow face; a high forehead; flushed (reddened) cheeks; and a small, pointed chin. In addition, the outside corners of the eyes may point downward (down-slanting palpebral fissures). This facial appearance is most notable in early childhood. Affected infants and children tend to grow quickly; they are significantly taller than their siblings and peers and have an unusually large head. However, adult height is usually in the normal range.People with Sotos syndrome often have intellectual disability, and most also have behavioral problems. Frequent behavioral issues include attention deficit hyperactivity disorder (ADHD), phobias, obsessions and compulsions, tantrums, and impulsive behaviors. Problems with speech and language are also common. Affected individuals often have a stutter, a monotone voice, and problems with sound production. Additionally, weak muscle tone (hypotonia) may delay other aspects of early development, particularly motor skills such as sitting and crawling.Other signs and symptoms of Sotos syndrome can include an abnormal side-to-side curvature of the spine (scoliosis), seizures, heart or kidney defects, hearing loss, and problems with vision. Some infants with this disorder experience yellowing of the skin and whites of the eyes (jaundice) and poor feeding.A small percentage of people with Sotos syndrome have developed cancer, most often in childhood, but no single form of cancer occurs most frequently with this condition. It remains uncertain whether Sotos syndrome increases the risk of specific types of cancer. If people with this disorder have an increased cancer risk, it is only slightly greater than that of the general population.
A rare autosomal dominant syndrome caused by mutations in the IRF6 gene. It is characterized by a cleft palate and/or pits on the lower lip. Other signs and symptoms include absent teeth, palate and tongue deformities.
Classic Saethre-Chotzen syndrome (SCS) is characterized by coronal synostosis (unilateral or bilateral), facial asymmetry (particularly in individuals with unicoronal synostosis), strabismus, ptosis, and characteristic appearance of the ear (small pinna with a prominent superior and/or inferior crus). Syndactyly of digits two and three of the hand is variably present. Cognitive development is usually normal, although those with a large genomic deletion are at an increased risk for intellectual challenges. Less common manifestations of SCS include other skeletal findings (parietal foramina, vertebral segmentation defects, radioulnar synostosis, maxillary hypoplasia, ocular hypertelorism, hallux valgus, duplicated or curved distal hallux), hypertelorism, palatal anomalies, obstructive sleep apnea, increased intracranial pressure, short stature, and congenital heart malformations.
Symphalangism, synostoses of the tarsal and carpal bones and other abnormalities, including orofacial defects and delayed mental development occurring alone or as a component of other syndromes.
Aarskog-Scott syndrome, also known as faciogenital dysplasia, is an X-linked disorder characterized by short stature, hypertelorism, shawl scrotum, and brachydactyly, although there is wide phenotypic variability and other features, such as joint hyperextensibility, short nose, widow's peak, and inguinal hernia, may also occur. Most patients do not have mental retardation, but some may have neurobehavioral features. Carrier females may present with subtle features, such as widow's peak or short stature (summary by Orrico et al., 2010).
Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvar aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty). Feeding difficulties often lead to poor weight gain in infancy. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones.
Thrombocytopenia absent radius (TAR) syndrome is characterized by bilateral absence of the radii with the presence of both thumbs and thrombocytopenia (<50 platelets/nL) that is generally transient. Thrombocytopenia may be congenital or may develop within the first few weeks to months of life; in general, thrombocytopenic episodes decrease with age. Cow's milk allergy is common and can be associated with exacerbation of thrombocytopenia. Other anomalies of the skeleton (upper and lower limbs, ribs, and vertebrae), heart, and genitourinary system (renal anomalies and agenesis of uterus, cervix, and upper part of the vagina) can occur.
Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features, including widely spaced eyes and ptosis. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with NSML do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (HCM) (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth retardation resulting in short stature occurs in fewer than 50% of affected persons, although most affected individuals have a height that is less than the 25th percentile for age. Sensorineural hearing deficits, present in approximately 20%, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML.
Right atrial isomerism is a severe complex congenital heart defect resulting from embryonic disruption of proper left-right axis determination. RAI is usually characterized by complete atrioventricular septal defect with a common atrium and univentricular AV connection, total anomalous pulmonary drainage, and transposition or malposition of the great arteries. Affected individuals present at birth with severe cardiac failure. Other associated abnormalities include bilateral trilobed lungs, midline liver, and asplenia, as well as situs inversus affecting other organs. Left atrial isomerism (LAI) is a related disorder with a somewhat better prognosis. LAI is characterized by bilateral superior vena cava, interruption of the intrahepatic portion of the inferior vena cava, partial anomalous pulmonary venous drainage, and ventricular septal defect. Patients with LAI may have polysplenia and bilateral bilobed lungs, as well as situs inversus affecting other organs. Both RAI and LAI malformation complexes have classically been referred to as Ivemark syndrome (summary by Eronen et al., 2004 and Kaasinen et al., 2010).
Aicardi syndrome was classically characterized by a triad of features: agenesis of the corpus callosum, distinctive chorioretinal lacunae, and infantile spasms. However, it is now well recognized that several other important findings are typically present in girls with Aicardi syndrome. Neurologic examination can reveal microcephaly, axial hypotonia, and appendicular hypertonia with spasticity. Moderate to severe global developmental delay and intellectual disability are expected. Many girls with Aicardi syndrome develop seizures prior to age three months, and most before age one year. Ongoing medically refractory epilepsy with a variety of seizure types develops over time. Costovertebral defects are common and can lead to marked scoliosis in up to one third of affected individuals. Other features include characteristic facial features, gastrointestinal difficulties, small hands, vascular malformations and pigmentary lesions of the skin, increased incidence of tumors, lower growth rate after ages seven to nine years, and precocious or delayed puberty. Survival is highly variable, with the mean age of death about 8.3 years and the median age of death about 18.5 years.
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
A growth disorder of the tibia in children and adolescents that presents as progressive bowing of one or both legs.
Larsen syndrome is a disorder that affects the development of bones throughout the body. The signs and symptoms of Larsen syndrome vary widely even within the same family. Affected individuals are usually born with inward- and upward-turning feet (clubfeet) and dislocations of the hips, knees, and elbows. They generally have small extra bones in their wrists and ankles that are visible on x-ray images. The tips of their fingers, especially the thumbs, are typically blunt and square-shaped (spatulate).People with Larsen syndrome may also have an unusually large range of joint movement (hypermobility) and short stature. They can also have abnormal curvature of the spine (kyphosis or scoliosis) that may compress the spinal cord and lead to weakness of the limbs.Characteristic facial features include a prominent forehead (frontal bossing), flattening of the bridge of the nose and of the middle of the face (midface hypoplasia), and wide-set eyes (ocular hypertelorism). Some people with Larsen syndrome have an opening in the roof of the mouth (a cleft palate) or hearing loss caused by malformations in the tiny bones in the ears (ossicles). Some affected individuals experience respiratory problems as a result of weakness of the airways that can lead to partial closing, short pauses in breathing (apnea), and frequent respiratory infections. People with Larsen syndrome can survive into adulthood and intelligence is unaffected.
A protrusion of abdominal structures through the retaining ABDOMINAL WALL. It involves two parts: an opening in the abdominal wall, and a hernia sac consisting of PERITONEUM and abdominal contents. Abdominal hernias include groin hernia (HERNIA, FEMORAL; HERNIA, INGUINAL) and VENTRAL HERNIA.
Impaired ability of an infant to suck or coordinate the suck-swallow response resulting in inadequate oral nutrition for metabolic needs.
Anemia with varying degrees of erythrocytic hypoplasia without leukopenia or thrombocytopenia.
A benign biphasic tumor of the breast with epithelial and stromal components.
A rare, lethal congenital malformation characterized by bilateral renal agenesis and the absence or decreased volume of amniotic fluid (oligohydramnios). The presence of oligohydramnios gives rise to congenital anomalies that include hypoplastic lungs, lower extremities abnormalities, and characteristic facial features (low-set ears, widely separated eyes, nose flattening, and receding chin). Newborn infants usually die of respiratory failure.
localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion; frequently occurs in conjunction with brain hypoxia, which is reduction in brain oxygen supply; severe hypoxia is referred to as anoxia.
A category of psychiatric disorders which includes disorders most commonly identified in infancy, childhood, or adolescence.
Any agent that binds to and activates dopamine receptors.
chelating agent that binds calcium and heavy metal ions; used as an anticoagulant for blood specimens and for treatment of lead poisoning and hypercalcemia.
A cofactor for 1-carbon transfer involved with DNA synthesis.
amino acid formed in the metabolism of L-glutamic acid; it is the major inhibitory neurotransmitter in the central nervous system, and is also found in some extraneural tissue including kidney and pancreatic islet cells.
heterogeneous group of immunoglobulin disease characterized by the presence in serum or urine of a paraprotein (monoclonal gammopathy) or two distinct paraproteins (biclonal gammopathy).
A hardening of the kidney glomerulus caused by scarring of the blood vessels.
condition in which there is a deviation from or interruption of the normal structure or function of the hair follicle, which is a tube-like invagination of the epidermis from which the hair shaft develops.
poly(acetylglucosamine-glucuronic acid), a highly adhesive mucopolysaccharide found in the intercellular cementing substance of skin and other tissues.
two types, primary type is a condition chiefly characterized by thickening of the skin of the head and distal extremities, deep folds and furrows of the skin of the forehead, cheeks, and scalp, seborrhea, hyperhidrosis, periostosis of the long bones, digital clubbing, and spadelike enlargement of the hands and feet, it is more prevalent in the male; secondary type is a condition with symmetrical osteitis of the four limbs, chiefly localized to the phalanges and the terminal epiphyses of the long bones of the forearm and leg, sometimes extending to the proximal ends of the limbs and the flat bones, and accompanied by dorsal kyphosis and joint involvement, and is often secondary to chronic conditions of the lungs and heart.
pain in the oral and/or facial regions; associated conditions include local inflammatory and neoplastic disorders and neuralgic syndromes involving the trigeminal, facial, and glossopharyngeal nerves.
condition of the patient preceding surgery.
excess of blood in a body part following restoration of its temporarily arrested flow.
A non-neoplastic or neoplastic disorder that affects the male or female genital system. Representative examples of non-neoplastic disorders include infection, testicular torsion, endometriosis, and adenomyosis. Representative examples of neoplastic disorders include germ cell tumors, carcinoma, lymphoma, and sarcoma.
A benign or malignant, primary or metastatic neoplasm affecting the male and female reproductive system.
A pathologic process in which alterations at the molecular level result in a more aggressive cytologic and phenotypic profile and clinical course of a neoplasm.
Blockage of the normal flow of contents of the urinary tract.
An agent that contains a radioactive isotope and is used for diagnostic or therapeutic purposes.
Condition did not change and required not further care to maintain condition
Change in or modification of energy used by the body
Change in or modification of the muscles, bones or support structures
Cardiovascular Alteration involves a change in the existing function of biologic molecules and complexes, or cellular, cell, or tissue components of the heart and vascular system by which blood is pumped and circulated through the body to provide tissues with oxygen and nutrients and to remove waste products.
Change in or modification of mental processes
Increased chance of fluid retention, overload, or edema
Failure to follow regulated course of treating disease
Change in or modification of the immune system
Change in or modification of food or nutrients
Increased chance of less than adequate intake or absorption of food or nutrients
Change in or modification of the breathing function
Group of symptoms related to effects of immobility
Change in modification of ability to maintain oneself
Change in or modification of more complex activities than those needed to maintain oneself
Change in or modification of the ability to see the significance, purpose, or,value in something
Change in or modification of diminished balance
Change in or modification of diminished ability to feel
A sensation of discomfort or distress that has a severe or rapid onset.
Change in or modification of neurovascularization of the extremities
Change in or modification of the kidney function
An alkaloid found in the seeds of STRYCHNOS NUX-VOMICA. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison.
Having a high degree of severity. For quantitative traits, a deviation of between four and five standard deviations from the appropriate population mean.
An absence finding of the specified component / analyte, organism or clinical sign based on the established threshold of the performed test or procedure. [Note: Negative does not necessarily imply the complete absence of the specified item.].
Deviating in any way from the state, position, structure, condition, behavior, or rule which is considered a norm.
The state of being confined to jail or prison.
A test result that shows evidence of a result or condition although it is not actually present.
Minimal invasion by malignant cells of the tissues that are immediately adjacent to a carcinoma in situ.
An adenocarcinoma characterized by the presence of large malignant epithelial cells with abundant granular eosinophilic cytoplasm (oncocytes). Representative examples include thyroid gland oncocytic follicular carcinoma, oncocytic breast carcinoma, and salivary gland oncocytic carcinoma.
A carcinoma characterized by the presence of a cribriform architectural pattern. Representative examples include the intraductal cribriform breast carcinoma and invasive cribriform breast carcinoma.
An adenocarcinoma characterized by the presence of malignant epithelial cells with granular cytoplasm.
An infiltrating adenocarcinoma in which the malignant cells form tubular structures. Representative examples include the tubular breast carcinoma and the gastric tubular adenocarcinoma.
A benign epithelial neoplasm with a uniform, monomorphic appearance that is dominated by basal cells forming trabecular structures. It is rare, and occurs mostly on the parotid gland. The average age of patients has been reported to be 58 years. Swelling is the most constant clinical finding.
A benign epithelial neoplasm characterized by a microcystic pattern. The cystic spaces are lined by small cuboidal cells without evidence of significant cytologic atypia.
A benign epithelial neoplasm arising from the salivary glands. It is characterized by the presence of a monomorphic cellular infiltrate.
An adenoma characterized by the presence of papillary epithelial patterns.
A benign epithelial neoplasm characterized by the presence of a trabecular glandular architectural pattern.
An invasive mixed adenoneuroendocrine carcinoma of the appendix characterized by a submucosal growth and the presence of neoplastic signet-ring cells resembling goblet cells of the intestine.
A malignant epithelial neoplasm characterized by the presence of spindle cells and anaplastic morphologic features. Giant cells and a sarcomatous component may also be present.
A usually aggressive malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular, squamous, or transitional cell differentiation.
Carcinoma that has spread diffusely to an anatomic site or throughout the body.
Hypertrophic cardiomyopathy with an asymmetrical pattern of hypertrophy, with a predilection for the interventricular septum and myocyte disarray.
Dried aged bark of a buckthorn, Frangula purshiana (RHAMNUS), that contains the anthraquinone EMODIN and cascarosides. It is used as a laxative (CATHARTICS).
A concentrated mixture of anthranol glycosides derived from cascara sagrada.
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life and about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataracts (in what has been called ""chronic progressive external ophthalmoplegia plus,"" or ""CPEO+"").
PLP1-related disorders of central nervous system myelin formation include a range of phenotypes from Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). PMD typically manifests in infancy or early childhood with nystagmus, hypotonia, and cognitive impairment; the findings progress to severe spasticity and ataxia. Life span is shortened. SPG2 manifests as spastic paraparesis with or without CNS involvement and usually normal life span. Intrafamilial variation of phenotypes can be observed, but the signs are usually fairly consistent within families. Female carriers may manifest mild to moderate signs of the disease.
An infection acquired in a hospital or other healthcare setting.
A large pigmented lesion measuring 5-15 mm in diameter with irregular, notched, and ill defined border and with color that may range from tan to dark brown to pink. [HPO:probinson]
A racemic mixture of d-epinephrine and l-epinephrine.
A soft tissue tumor of uncertain lineage characterized by the presence of neoplastic spindle-shaped to round cells in a fibromyxoid stroma. Metaplastic bone formation may or may not be present.
A benign, slowly growing tumor (WHO grade I) typically arising in the wall of the lateral ventricles and composed of large ganglioid astrocytes. It is the most common CNS neoplasm in patients with tuberous sclerosis complex and typically occurs during the first two decades of life. (WHO)
A slow growing, WHO grade I glioma which generally occurs in young adults. It arises almost exclusively in the conus medullaris, cauda equina, and filum terminale of the spinal cord. It generally has a favorable prognosis and is characterized histologically by tumor cells arranged in a papillary manner around vascularized mucoid stromal cores. (Adapted from WHO).
Choroid plexus tumors are of neuroectodermal origin and range from benign choroid plexus papillomas (CPPs) to malignant choroid carcinomas (CPCs). These rare tumors generally occur in childhood, but have also been reported in adults. Patients typically present with signs and symptoms of increased intracranial pressure including headache, hydrocephalus, papilledema, nausea, vomiting, cranial nerve deficits, gait impairment, and seizures (summary by Safaee et al., 2013).
A hemangioma characterized by the presence of epithelioid endothelial cells.
A hemangioma arising from skeletal muscle.
potent excitatory amino acid agonist and neurotoxin from the seaweed Diginea simplex.
A morphologic variant of leiomyosarcoma characterized by the presence of epithelioid round cells with eosinophilic to clear cytoplasm.
A morphologic variant of leiomyosarcoma characterized by the presence of cellular pleomorphism, malignant cells with large nuclei, and a myxoid stroma.
A rare benign slow growing adipose tissue tumor, characterized by the presence of polygonal brown fat cells with multivacuolated and/or granular cytoplasm. The tumor is usually painless and is most often seen in young adults.
A benign circumscribed tumor characterized by small spindle cells, rounded hyperchromatic cells and multinucleated giant cells with radially arranged nuclei.
An atypical lipomatous tumor/well differentiated liposarcoma that shows progression to a usually non-lipomatous, high grade sarcoma. The non-lipomatous sarcoma component may be present in the primary lesion or at the site of recurrence.
A liposarcoma characterized by the presence of varying proportions of pleomorphic lipoblasts in a background that resembles undifferentiated pleomorphic sarcoma. It is the rarest liposarcoma variant and usually has an aggressive clinical course.
A lymphangioma characterized by the presence of thin-walled cavernous lymphatic spaces.
A rare malignant embryonal neoplasm arising from the cerebellum. It is characterized by the morphologic features of a medulloblastoma and the presence of a striated muscle component. Its clinical behavior is similar to medulloblastoma.
The presence of multiple meningiomas in the leptomeninges.
The hydrochloride salt of the partial estrogen antagonist nafoxidine. Nafoxidine competes with endogenous estrogen for binding to specific estrogen receptors. This agent also inhibits angiogenesis in some tissues by blocking the effects of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF); paradoxically, it may enhance angiogenesis in uterine tissue. Nafoxidine also induces oxidative stress, protein kinase C and calcium signaling. (NCI04)
A benign or malignant, gonadal or extragonadal neoplasm that originates from germ cells. Representative examples include teratoma, seminoma, embryonal carcinoma, and yolk sac tumor.
A rare benign neoplasm arising from tooth-forming tissues. It is characterized by the presence of a fibromyxoid stroma, epithelial component, dentin, and enamel. Recurrences are rare.
A benign, slow growing, and painless hamartomatous tumor occurring in tooth-bearing areas of the jaws. It usually affects children and adolescents. It is characterized by the presence of tooth-like structures. Treatment consists of local excision. Recurrences have not been reported.
A benign epithelial neoplasm characterized by a papillary growth pattern and a proliferation of neoplastic squamous cells without morphologic evidence of malignancy [NCI thesaurus].
Glandular or squamous cell neoplastic proliferations characterized by the formation of multiple papillary structures diffusely involving a specific anatomic site.
A poorly differentiated malignant embryonal neoplasm arising from the pineal region. It usually occurs in children and it is characterized by the presence of small immature neuroepithelial cells. It may follow an aggressive clinical course.
The hydrochloride salt of a methylhydrazine derivative with antineoplastic and mutagenic activities. Although the exact mode of cytotoxicity has not been elucidated, procarbazine, after metabolic activation, appears to inhibit the trans-methylation of methionine into transfer RNA (t-RNA), thereby preventing protein synthesis and consequently DNA and RNA synthesis. This agent may also undergo auto-oxidation, resulting in the formation of cytotoxic free radicals which damage DNA through an alkylation reaction.
A class of cyclic prostaglandins that contain the 6,9-epoxy bond. Endogenous members of this family are biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES.
An abnormal connection between the epithelialised surface of the anal canal and the perianal skin.
An aggressive malignant neoplasm of uncertain differentiation, characterized by the presence of epithelioid cells forming nodular patterns. The nodules often undergo central necrosis, resulting in a pseudogranulomatous growth pattern. It usually occurs in young adults. The most common sites of involvement are the extremities (distal-type epithelioid sarcoma), and less frequently the pelvis, perineum, and genital organs (proximal-type epithelioid sarcoma).
A malignant mesenchymal neoplasm composed of spindle-shaped cells. This is a morphologic term which can be applied to a wide range of sarcomas.
A thymoma that has an aggressive clinical course (capsular invasion, infiltration of the surrounding tissues) and can metastasize. Although any morphologic subtype of thymoma may eventually have a malignant clinical course, this term is most often associated with thymoma types B3 and C.
Inflammation of interstitial lung tissue, usually associated with infection.
A diverse group of lung diseases that affect the lung parenchyma. They are characterized by an initial inflammation of PULMONARY ALVEOLI that extends to the interstitium and beyond leading to diffuse PULMONARY FIBROSIS. Interstitial lung diseases are classified by their etiology (known or unknown causes), and radiological-pathological features.
ANGINA PECTORIS or angina-like chest pain with a normal coronary arteriogram and positive EXERCISE TEST. The cause of the syndrome is unknown. While its recognition is of clinical importance, its prognosis is excellent. (Braunwald, Heart Disease, 4th ed, p1346; Jablonski Dictionary of Syndromes & Eponymic Diseases, 2d ed). It is different from METABOLIC SYNDROME X, a syndrome characterized by INSULIN RESISTANCE and HYPERINSULINEMIA, that has increased risk for cardiovascular disease.
Hyperplasia characterized by the presence of a focal proliferation of epithelial cells.
A cardiac arrhythmia that is caused by interaction of two independently initiated cardiac impulses of different rates from two separate foci. Generally one focus is the SINOATRIAL NODE, the normal pacemaker. The ectopic focus is usually in the HEART VENTRICLE but can be in the HEART ATRIUM or the ATRIOVENTRICULAR NODE. Modulation of the parasystolic rhythm by the sinus rhythm depends on the completeness of entrance block surrounding the parasystolic focus.
Deliberate, often repetitive physical, verbal, and/or other types of abuse by one or more members against others of a household.
An account of all reproductive events and problems a person has experienced. An important aggregate factor in epidemiological studies of women's health. The concept usually includes the number and timing of pregnancies and their outcomes, the incidence of breast feeding, and may include age of menarche and menopause, regularity of menstruation, fertility, gynecological or obstetric problems, or contraceptive usage.
A condition caused by the excessive secretion of ANDROGENS from the ADRENAL CORTEX; the OVARIES; or the TESTES. The clinical significance in males is negligible. In women, the common manifestations are HIRSUTISM and VIRILISM as seen in patients with POLYCYSTIC OVARY SYNDROME and ADRENOCORTICAL HYPERFUNCTION.
A central nervous system disorder caused by demyelination within the central basis pontis of the brain. It is characterized by spastic quadriplegia, pseudobulbar palsy and encephalopathy. It is observed in patients with severe hyponatremia, particularly when the hyponatremia is corrected too rapidly.
The Kleine-Levin hibernation syndrome, a rare disorder that occurs predominantly in males, is characterized by episodic attacks of aberrant behavior, hypersomnia, and increased feeding (megaphagia) and sex drives (Kleine, 1925; Levin, 1929).
A neoplasm arising in the neuroectoderm, the portion of the ectoderm of the early embryo that gives rise to the central and peripheral nervous systems, including some glial cells.
A rare neoplasm usually occurring in infants. It is characterized by the presence of a mixture of melanin-containing epithelial cells and smaller neuroblast-like cells. It may involve the skull and facial bones, or the epididymis. It usually has a benign clinical course.
Loss or destruction of periodontal tissue caused by periodontitis or other destructive periodontal diseases or by injury during instrumentation. Attachment refers to the periodontal ligament which attaches to the alveolar bone. It has been hypothesized that treatment of the underlying periodontal disease and the seeding of periodontal ligament cells enable the creating of new attachment.
PAX6-related aniridia occurs either as an isolated ocular abnormality or as part of the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome. Aniridia is a pan ocular disorder affecting the cornea, iris, intraocular pressure (resulting in glaucoma), lens (cataract and lens subluxation), fovea (foveal hypoplasia), and optic nerve (optic nerve coloboma and hypoplasia). Individuals with aniridia characteristically show nystagmus and impaired visual acuity (usually 20/100 - 20/200); however, milder forms of aniridia with subtle iris architecture changes, good vision, and normal foveal structure do occur. Other ocular involvement may include strabismus and occasionally microphthalmia. Although the severity of aniridia can vary between and within families, little variability is usually observed in the two eyes of an affected individual. WAGR syndrome. The risk for Wilms tumor is 42.5%-77%; of those who develop Wilms tumor, 90% do so by age four years and 98% by age seven years. Genital anomalies in males can include cryptorchidism and hypospadias (sometimes resulting in ambiguous genitalia), urethral strictures, ureteric abnormalities, and gonadoblastoma. While females typically have normal external genitalia, they may have uterine abnormalities and streak ovaries. Intellectual disability (defined as IQ <74) is observed in 70%; behavioral abnormalities include attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, anxiety, depression, and obsessive-compulsive disorder. Other individuals with WAGR syndrome can have normal intellect without behavioral problems.
A mild form of LIMITED SCLERODERMA, a multi-system disorder. Its features include symptoms of CALCINOSIS; RAYNAUD DISEASE; ESOPHAGEAL MOTILITY DISORDERS; sclerodactyly, and TELANGIECTASIS. When the defect in esophageal function is not prominent, it is known as CRST syndrome.
A chronic, autoimmune inflammatory condition of the mucous membranes in the oral cavity that affects approximately two percent of the population and is most often seen in middle aged women. It is characterized by white, lacy patches; red, swollen tissue; papules and plaques; or open sores. The lesions are typically bilateral.
PDGFRA-associated chronic eosinophilic leukemia is a form of blood cell cancer characterized by an elevated number of cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRA-associated chronic eosinophilic leukemia.Another characteristic feature of PDGFRA-associated chronic eosinophilic leukemia is organ damage caused by the excess eosinophils. Eosinophils release substances to aid in the immune response, but the release of excessive amounts of these substances causes damage to one or more organs, most commonly the heart, skin, lungs, or nervous system. Eosinophil-associated organ damage can lead to a heart condition known as eosinophilic endomyocardial disease, skin rashes, coughing, difficulty breathing, swelling (edema) in the lower limbs, confusion, changes in behavior, or impaired movement or sensations. People with PDGFRA-associated chronic eosinophilic leukemia can also have an enlarged spleen (splenomegaly) and elevated levels of certain chemicals called vitamin B12 and tryptase in the blood.Some people with PDGFRA-associated chronic eosinophilic leukemia have an increased number of other types of white blood cells, such as neutrophils or mast cells. Occasionally, people with PDGFRA-associated chronic eosinophilic leukemia develop other blood cell cancers, such as acute myeloid leukemia or B-cell or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma.PDGFRA-associated chronic eosinophilic leukemia is often grouped with a related condition called hypereosinophilic syndrome. These two conditions have very similar signs and symptoms; however, the cause of hypereosinophilic syndrome is unknown.
Loeffler's endocarditis is a rare restrictive cardiomyopathy (see this term) characterized by hypereosinophilia and fibrous thickening of the endocardium, with usually large thrombi against the ventricle walls, that can lead to cardiovascular complications such as heart failure and thromboembolism. It manifests with symptoms like edema, fatigue and shortness of breath. It is usually secondary to eosinophil-associated tissue damage and is associated with idiopathic hypereosinophilic syndrome, chronic eosinophilic leukemia (see these terms), carcinoma, or lymphoma.
Prolonged dysfunction of the myocardium after a brief episode of severe ischemia, with gradual return of contractile activity.
An old term that is no longer used in the scientific literature. Cholera morbus refers to acute GASTROENTERITIS occurring in summer or autumn; characterized by severe cramps, diarrhea, and vomiting.
Nemaline myopathy (referred to in this entry as NM) is characterized by weakness, hypotonia, and depressed or absent deep tendon reflexes. Muscle weakness is usually most severe in the face, the neck flexors, and the proximal limb muscles. The clinical classification defines six forms of NM, which are classified by onset and severity of motor and respiratory involvement: Severe congenital (neonatal) (16% of all individuals with NM). Amish NM. Intermediate congenital (20%). Typical congenital (46%). Childhood-onset (13%). Adult-onset (late-onset) (4%). Considerable overlap occurs among the forms. There are significant differences in survival between individuals classified as having severe, intermediate, and typical congenital NM. Severe neonatal respiratory disease and the presence of arthrogryposis multiplex congenita are associated with death in the first year of life. Independent ambulation before age 18 months is predictive of survival. Most children with typical congenital NM are eventually able to walk.
An elevation in the number of reticulocytes (immature erythrocytes) in the peripheral blood circulation.
Any infection acquired in the community, that is, contrasted with those acquired in a health care facility (CROSS INFECTION). An infection would be classified as community-acquired if the patient had not recently been in a health care facility or been in contact with someone who had been recently in a health care facility.
Common foot problems in persons with DIABETES MELLITUS, caused by any combination of factors such as DIABETIC NEUROPATHIES; PERIPHERAL VASCULAR DISEASES; and INFECTION. With the loss of sensation and poor circulation, injuries and infections often lead to severe foot ulceration, GANGRENE and AMPUTATION.
The pressure within a CARDIAC VENTRICLE. Ventricular pressure waveforms can be measured in the beating heart by catheterization or estimated using imaging techniques (e.g., DOPPLER ECHOCARDIOGRAPHY). The information is useful in evaluating the function of the MYOCARDIUM; CARDIAC VALVES; and PERICARDIUM, particularly with simultaneous measurement of other (e.g., aortic or atrial) pressures.
Infection of the retina by cytomegalovirus characterized by retinal necrosis, hemorrhage, vessel sheathing, and retinal edema. Cytomegalovirus retinitis is a major opportunistic infection in AIDS patients and can cause blindness.
A peripheral (mature) T-cell lymphoma, consisting of usually large anaplastic, CD30 positive cells. The majority of cases are positive for the anaplastic large cell lymphoma (ALK) protein. The most frequently seen genetic alteration is a t(2;5) translocation. Majority of patients present with advanced disease. The most important prognostic indicator is ALK positivity, which has been associated with a favorable prognosis. (WHO, 2001)
A chronic, recurrent cutaneous disorder characterized by the presence of spontaneously regressing papules. The papules are composed of an atypical lymphocytic infiltrate that contains anaplastic CD30-positive T-cells, which are found in type A and diffuse large cell type (type C) lymphomatoid papulosis. In a small number of cases, of type B, the lymphocytic infiltrate is composed of small, cerebriform-like lymphocytes that are often negative for CD30. The majority of cases follow a benign clinical course, but some cases are clonal and may progress to lymphoma. Treatment options include low dose methotrexate and psoralen/UVA (PUVA).
A corrugated white lesion of the oral mucosa that usually occurs on the lateral or ventral surfaces of the tongue and may have a shaggy or frayed appearance.
The transmission of infectious disease or pathogens from health professional or health care worker to patients. It includes transmission via direct or indirect exposure to bacterial, fungal, parasitic, or viral agents.
The transmission of infectious disease or pathogens from patients to health professionals or health care workers. It includes transmission via direct or indirect exposure to bacterial, fungal, parasitic, or viral agents.
Displacement of bones out of line in relation to joints. It may be congenital or traumatic in origin.
A heparin fraction with a mean molecular weight of 4500 daltons. It is isolated from porcine mucosal heparin and used as an antithrombotic agent. (From Merck Index, 11th ed)
Ulnar neuropathies caused by mechanical compression of the nerve at any location from its origin at the BRACHIAL PLEXUS to its terminations in the hand. Common sites of compression include the retroepicondylar groove, cubital tunnel at the elbow (CUBITAL TUNNEL SYNDROME), and Guyon's canal at the wrist. Clinical features depend on the site of injury, but may include weakness or paralysis of wrist flexion, finger flexion, and ulnar innervated intrinsic hand muscles, and impaired sensation over the ulnar aspect of the hand, fifth finger, and ulnar half of the ring finger. (Joynt, Clinical Neurology, 1995, Ch51, p43)
A rare inherited neuropathy characterized by deposition of amyloid in the peripheral nerves.
Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. Familial, primary (nonfamilial), and secondary forms have been described. Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. Clinical manifestations include sensory loss, mild weakness, autonomic dysfunction, and CARPAL TUNNEL SYNDROME. (Adams et al., Principles of Neurology, 6th ed, p1349)
Two or more vaccines in a single dosage form.
Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.
An unmarried person whose spouse has died
Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from DEATH, the physiological cessation of life and from MORTALITY, an epidemiological or statistical concept.
Conditions in which a bifurcation or trifurcation of the molar tooth root becomes denuded as a result of periodontal disease. It may be followed by tooth mobility, temperature sensitivity, pain, and alveolar bone resorption.
Most individuals with Canavan disease have the neonatal/infantile form. Although such infants appear normal early in life, by age three to five months, hypotonia, head lag, macrocephaly, and developmental delays become apparent. With age, children with neonatal/infantile-onset Canavan disease often become irritable and experience sleep disturbance, seizures, and feeding difficulties. Swallowing deteriorates, and some children require nasogastric feeding or permanent feeding gastrostomies. Joint stiffness increases, so that these children resemble individuals with cerebral palsy. Children with mild/juvenile Canavan disease may have normal or mildly delayed speech or motor development early in life without regression. In spite of developmental delay most of these children can be educated in typical classroom settings and may benefit from speech therapy or tutoring as needed. Most children with mild forms of Canavan disease have normal head size, although macrocephaly, retinitis pigmentosa, and seizures have been reported in a few individuals.
The co-existence of a substance abuse disorder with a psychiatric disorder. The diagnostic principle is based on the fact that it has been found often that chemically dependent patients also have psychiatric problems of various degrees of severity.
A calcification of the posterior longitudinal ligament of the spinal column, usually at the level of the cervical spine. It is often associated with anterior ankylosing hyperostosis.
Exfoliation syndrome (XFS) is a common age-related disorder of the extracellular matrix that is frequently associated with severe chronic secondary open-angle glaucoma and cataract. XFS syndrome may affect up to 30% of people over 60 years of age worldwide and is biomicroscopically diagnosed by abnormal microfibrillar deposits on ocular structures that line the aqueous-bathed surfaces of the anterior segment (summary by Schlotzer-Schrehardt and Naumann, 2006).
The spontaneous transplantation of splenic tissue to unusual sites after open splenic trauma, e.g., after automobile accidents, gunshot or stab wounds. The splenic pulp implants appear as red-blue nodules on the peritoneum, omentum, and mesentery, morphologically similar to multifocal pelvic endometriosis. (Segen, Dictionary of Modern Medicine, 1992)
A low molecular weight, synthetic heparin. As an anticoagulant/antithrombotic agent, enoxaprin's mechanism of action is similar to that of heparin, although it exhibits a higher ratio of anti-Factor Xa to anti-Factor IIa activity. This agent also has anti-inflammatory properties, inhibiting monocyte adhesion to tumor necrosis factor alpha- or lipopolysaccharide-activated endothelial cells. Compared to unfractionated heparins, the use of enoxaparin is associated with lower incidences of osteoporosis and heparin-induced thrombocytopenia. (NCI04)
A low molecular weight, synthetic heparin. As an anticoagulant/antithrombotic agent, dalteparin binds to antithrombin and enhances the inhibition of Factor Xa. Compared to unfractionated heparins, the use of dalteparin is associated with lower incidences of osteoporosis and heparin-induced thrombocytopenia. (NCI04)
Any monoclonal antibody that targets two different antigens. A bispecific monoclonal antibody is made up of two different monoclonal antibodies or antibody fragments and contains two different antigen-binding sites.
Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors.
Vaccines or candidate vaccines containing antigenic polysaccharides from Haemophilus influenzae and designed to prevent infection. The vaccine can contain the polysaccharides alone or more frequently polysaccharides conjugated to carrier molecules. It is also seen as a combined vaccine with diphtheria-tetanus-pertussis vaccine.
A category of vaccines created by covalently attaching an antigen from an organism to a carrier protein from the same organism to aid in the delivery of the immunogen.
Tuberculosis disease that is caused by a multidrug-resistant strain of Mycobacterium tuberculosis.
A localized arrested tooth development which appears to involve most commonly the anterior teeth, usually on one side of the midline, most often the maxillary central and lateral incisors. Roentgenographically, the teeth have a ghostlike appearance. Calcification and bits of prismatic enamel may be found in the pulp and the enamel is thin and absent in part. (Jablonski, Illustrated Dictionary of Dentistry, 1982)
An accumulation of ENDOLYMPH in the inner ear (LABYRINTH) leading to buildup of pressure and distortion of intralabyrinthine structures, such as COCHLEA and SEMICIRCULAR CANALS. It is characterized by SENSORINEURAL HEARING LOSS; TINNITUS; and sometimes VERTIGO.
The succinate salt form of sumatriptan, a member of the triptan class of compounds with anti-migraine property. Sumatriptan succinate selectively binds to and activates serotonin 5-HT1 receptors. This results in constriction of meningeal, dural, cerebral or pial blood vessels via stimulation of the 5-HT1B receptors, thereby reducing the vascular pulsation and may provide relief in migraine headaches. Furthermore, agonistic action of this agent through presynaptic stimulation of 5-HT1D and/or 5-HT1F receptors prevents release of vasoactive and pro-inflammatory neuropeptide (calcitonin gene-related peptide), thereby may also relieve migraine headaches. In addition, central inhibition of pain transmission via the inhibition of trigeminal neurons in the brain stems and upper spinal cord mediated by 5-HT1B, 5-HT1D or 5-HT 1F receptors also aides in the alleviation of migraine pain.
Virus diseases caused by the CIRCOVIRIDAE.
Infections caused by viruses of the genus ARTERIVIRUS.
Virus diseases caused by the BIRNAVIRIDAE.
Infections with viruses of the genus TOROVIRUS, family CORONAVIRIDAE.
Infections with viruses of the genus FLAVIVIRUS, family FLAVIVIRIDAE.
Infections with viruses of the family FLAVIVIRIDAE.
Infections with viruses of the genus PESTIVIRUS, family FLAVIVIRIDAE.
Infections with viruses of the family PARAMYXOVIRIDAE. This includes MORBILLIVIRUS INFECTIONS; RESPIROVIRUS INFECTIONS; PNEUMOVIRUS INFECTIONS; HENIPAVIRUS INFECTIONS; AVULAVIRUS INFECTIONS; and RUBULAVIRUS INFECTIONS.
Infections with viruses of the genus MORBILLIVIRUS, family PARAMYXOVIRIDAE. Infections mainly cause acute disease in their hosts, although in some cases infection is persistent and leads to degenerative conditions.
Infections with viruses of the genus PNEUMOVIRUS, family PARAMYXOVIRIDAE. This includes RESPIRATORY SYNCYTIAL VIRUS INFECTIONS, an important cause of respiratory disease in humans.
Infections caused by viruses of the genus CARDIOVIRUS, family PICORNAVIRIDAE.
A benign or malignant neoplasm arising from the lymphatic vessels.
A benign lymphatic neoplasm usually arising from the neck and characterized by cystic dilation of the lymphatic vessels.
A benign neoplasm characterized by the presence of a glandular and a mesenchymal (fibromyomatous) component. It occurs in the uterine corpus and the cervix. A variant of adenomyoma associated with glandular architectural complexity is called atypical polypoid adenomyoma. Simple polypectomy is usually curative. Atypical polypoid adenomyoma may recur following polypectomy.
A carcinoma composed of malignant glandular cells and malignant squamous cells.
A kind of neoplasm of the liver that originates from immature liver precursor cells and macroscopically is composed of tissue resembling fetal or mature liver cells or bile ducts.
A malignant neoplasm composed of a carcinomatous epithelial component and a sarcomatous mesenchymal component. Representative examples include malignant mixed mesodermal (Mullerian) tumor of the female reproductive system and carcinosarcoma of the salivary gland and the lung.
A group of tumors affecting the female reproductive system, characterized by the presence of epithelial and stromal elements. It includes the following clinicopathological entities: adenofibroma, adenomyoma, Mullerian adenosarcoma, and malignant mixed mesodermal (Mullerian) tumor.
A solid, unencapsulated tumor of the KIDNEY composed of spindle mesenchymal cells that resemble FIBROBLASTS or muscle cells. The homogeneous mass typically extends into the renal parenchyma and replaces most of the kidney. In most cases, mesoblastic nephroma is benign and occurs in the fetus or newborn, and rarely in the older child or the adult.
A malignant neoplasm of the lung composed of tubular structures and immature mesenchymal elements, which may differentiate towards skeletal and smooth muscle, cartilage or a combination of muscle and cartilage. This is a nodular tumor found in the periphery of the lung. It can occur at any age. The prognosis is related to the stage of the disease at the time of resection. Pulmonary blastoma is divided into two subtypes: epithelial predominant and biphasic.
A malignant mesenchymal neoplasm that affects the uterine corpus, and rarely, the ovaries, cervix, and vagina. In the uterine corpus it is classified as low grade or high grade endometrial stromal sarcoma. In the remainder of the anatomic sites it is classified as low grade endometrioid stromal sarcoma.
A benign, intermediate, or malignant mesenchymal neoplasm composed of adipose (fatty) tissue.
A lipoma with prominent vascularity. The vascular tissue is more abundant at the periphery of the tumor and contains fibrin thrombi. It occurs more frequently in younger individuals as a painful subcutaneous nodule, often on the arms.
A neoplasm with perivascular epithelioid cell differentiation often associated with tuberous sclerosis. It is characterized by a mixture of epithelioid cells, smooth muscle, vessels, and mature adipose tissue. The kidney is the most common site of involvement. Other sites of involvement include the liver, lung, lymph nodes, and retroperitoneum. The vast majority of cases follow a benign clinical course. However, cases of metastatic angiomyolipomas with sarcomatoid features have been described.
Myxoid liposarcoma is a soft tissue tumor that tends to occur in the limbs (especially the thigh) of patients ranging in age from 35 to 55 years. It is defined by the presence of a hypocellular spindle cell proliferation set in a myxoid background, often with mucin pooling. Lipoblasts tend to be small and often monovacuolated and to cluster around vessels or at the periphery of the lesion (review by Dei Tos, 2000).
A benign soft tissue lesion arising from the adrenal gland. It is composed of mature adipose and hematopoietic/lymphoid tissues.
A multifocal benign neoplasm arising from bone or soft tissue. It is characterized by the presence of chondrocytes and is composed of hyaline cartilage.
A morphologic variant of chondrosarcoma arising from bone and soft tissue. It is characterized by the presence of malignant small round cells, biphasic growth pattern, and well differentiated hyaline cartilage. Clinical presentation includes pain and swelling. The clinical course is aggressive, with local recurrences and distant metastases.
A benign but locally aggressive tumor that arises from the bone and is composed of mononuclear cells admixed with macrophages and osteoclast-like giant cells. It usually arises from the ends of long bones or the vertebrae. Clinical presentation includes pain, edema, and decreased range of motion in the affected joint.
Neoplasms composed of bony tissue, whether normal or of a soft tissue which has become ossified. The concept does not refer to neoplasms located in bones.
A benign central bone tumor composed of fibrous connective tissue within which bone is formed.
An autosomal dominant neoplastic chondrogenic process affecting multiple sites. It is caused by mutations in the EXT1 or EXT2 genes. Grossly and microscopically, the lesions resemble an osteochondroma.
A low grade malignant bone-forming mesenchymal neoplasm arising from the surface of the bone. It usually affects the distal posterior femur, the proximal tibia, and proximal humerus. Painless swelling is the usual clinical sign. Most patients are young adults and the prognosis is usually excellent.
A benign, intermediate, or malignant mesenchymal neoplasm characterized by the presence of neoplastic fibroblasts.
A benign neoplasm composed of fibroblastic spindle cells in a whorled storiform pattern. It is characterized by the presence of foam cells, inflammatory cells, hemosiderin deposition and stromal hemorrhage.
A rare, benign, locally aggressive, osteolytic neoplasm. It is characterized by the presence of a rich collagenous stroma and spindle cells with minimal cellular atypia.
An insidious poorly circumscribed neoplasm arising from the deep soft tissues of the abdomen. It is characterized by the presence of elongated spindle-shaped fibroblasts, collagenous stroma formation, and an infiltrative growth pattern.
A sarcoma of the deep layers of the skin. The tumors are locally aggressive tends to recur but rarely metastatic. It can be classified into variants depending on the cell type tumors are derived from or by its characteristics: Pigmented variant from MELANIN-containing DERMAL DENDRITIC CELLS; Myxoid variant, myxoid STROMAL CELLS; Giant cell variant characterized by GIANT CELLS in the tumors; and Fibrosarcomatous variant chracterized by tumor areas histologically indistinguishable from FIBROSARCOMA.
A benign, multifocal, nodular and well-circumscribed neoplasm usually seen as a congenital neoplasm or in the first year of life. It is characterized by a biphasic growth pattern and is composed of small, undifferentiated mesenchymal cells associated with branching thin-walled vessels and more mature neoplastic spindle cells with abundant eosinophilic cytoplasm in a collagenous stroma.
A benign, borderline, or malignant neoplasm characterized by the presence of an epithelial and a fibrous component. Representative examples are fibroadenoma and phyllodes tumor.
An adenoma containing fibrous tissue. It should be differentiated from ADENOFIBROMA which is a tumor composed of connective tissue (fibroma) containing glandular (adeno-) structures. (From Dorland, 27th ed)
A rare malignant neoplasm with melanocytic differentiation characterized by the presence of polygonal or spindle shaped clear cells. This sarcoma usually affects the tendons and aponeuroses and is associated with a poor prognosis due to recurrences and metastases.
A sarcoma characterized by the presence of small round or elongated malignant cells with a small amount of cytoplasm.
A benign, slow-growing neoplasm that arises from the dermis or subcutaneous tissue. It is characterized by the presence of well-differentiated smooth muscle cells which are arranged around numerous vessels.
A condition characterized by the presence of numerous small benign smooth muscle neoplasms located throughout the body.
A form of RHABDOMYOSARCOMA occurring mainly in adolescents and young adults, affecting muscles of the extremities, trunk, orbital region, etc. It is extremely malignant, metastasizing widely at an early stage. Few cures have been achieved and the prognosis is poor. ""Alveolar"" refers to its microscopic appearance simulating the cells of the respiratory alveolus. (Holland et al., Cancer Medicine, 3d ed, p2188)
A form of RHABDOMYOSARCOMA arising primarily in the head and neck, especially the orbit, of children below the age of 10. The cells are smaller than those of other rhabdomyosarcomas and are of two basic cell types: spindle cells and round cells. This cancer is highly sensitive to chemotherapy and has a high cure rate with multi-modality therapy. (From Holland et al., Cancer Medicine, 3d ed, p2188)
Alveolar soft part sarcoma is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior (Lieberman et al., 1989; Ordonez, 1999). The typical histology of ASPS shows well-defined nests of cells with abundant pink cytoplasm. The loss of central cohesion produces a pseudoalveolar appearance (Ladanyi et al., 2001).
A benign or malignant myomatous neoplasm arising from smooth muscle.
A non-seminomatous malignant germ cell tumor characterized by the presence of large germ cells with abundant cytoplasm resembling epithelial cells, geographic necrosis, high mitotic activity, and pseudoglandular and pseudopapillary structures formation. It can arise from the testis, ovary, and extragonadal sites (central nervous system and mediastinum).
A malignant germ cell tumor arising in the central nervous system. It is characterized by the presence of primitive, large malignant germ cells and lymphocytes.
A complex neoplasm composed of a mixture of gonadal elements, such as large primordial GERM CELLS, immature SERTOLI CELLS or GRANULOSA CELLS of the sex cord, and gonadal stromal cells. Gonadoblastomas are most often associated with gonadal dysgenesis, 46, XY.
A group of malignant tumors of the nervous system that feature primitive cells with elements of neuronal and/or glial differentiation. Use of this term is limited by some authors to central nervous system tumors and others include neoplasms of similar origin which arise extracranially (i.e., NEUROECTODERMAL TUMORS, PRIMITIVE, PERIPHERAL). This term is also occasionally used as a synonym for MEDULLOBLASTOMA. In general, these tumors arise in the first decade of life and tend to be highly malignant. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2059)
A germ cell tumor characterized by the presence of an embryonal carcinoma component and a teratoma component.
A rare gestational trophoblastic tumor characterized by the presence of a diffuse cellular infiltrate composed of intermediate trophoblasts and cytotrophoblasts and by the absense of a significant population of syncytiotrophoblasts.
A benign neoplasm of the ADRENAL CORTEX. It is characterized by a well-defined nodular lesion, usually less than 2.5 cm. Most adrenocortical adenomas are nonfunctional. The functional ones are yellow and contain LIPIDS. Depending on the cell type or cortical zone involved, they may produce ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and/or ANDROSTENEDIONE.
A benign epithelial neoplasm arising from the hepatocytes. Grossly, it appears as a soft, round mass which often contains areas of hemorrhage and necrosis. Morphologically, the neoplastic cells resemble normal hepatocytes and form plates separated by sinusoids. Most patients have a history of contraceptive or anabolic steroids use.
A benign epithelial neoplasm arising from the sweat glands. It presents as a nodular lesion usually in the scalp, trunk, and proximal extremities. It is characterized by a nodular growth pattern. Complete excision is curative.
A benign cystic proliferation of the sweat glands with apocrine or eccrine differentiation. It usually presents as a dome-shaped, cystic papular or nodular lesion usually in the face and neck. It is a unilocular or mutlilocular lesion lined by an inner and an outer layer of epithelium. Complete excision is usually curative.
A benign sweat gland neoplasm usually affecting the lower eyelids and upper cheeks. The lesions are papular and are usually numerous. Morphologically, there are nests, cords, and tubules of epithelial cells present, surrounded by a dense stroma in the reticular dermis.
An epithelial neoplasm morphologically characterized by the presence of a villous architectural pattern. Most often it occurs in the large intestine, small intestine, and the stomach in which the neoplastic epithelial cells show dysplastic features. It may also arise in the urinary bladder, urethra, and vagina.
A benign neoplasm arising from mesothelial cells. It is characterized by the formation of glandular and tubular patterns. It can occur in several anatomic sites including the pleura, peritoneum, and epididymis.
This is a non-human neoplastic process described in sheep.
A polypoid neoplasm arising from the glandular epithelium. There is proliferation of glandular cells which may display dysplastic cytologic features. Representative examples include the adenomatous polyps of the colon and rectum.
An intermediate grade neoplasm arising from mesothelial cells. It occurs in the peritoneum, extraperitoneal space, omentum, or pelvic or abdominal viscera. It is characterized by the presence of multiple cysts lined by flattened or cuboidal mesothelial cells. There is no evidence of significant cytologic atypia or increased mitotic activity. It usually occurs in young to middle-aged women. Patients present with abdominal or pelvic mass and pain. Approximately half of the cases recur. The recurrences may appear several years after the initial diagnosis. Rare cases of transformation to malignant mesothelioma have also been described.
A malignant neoplasm composed of glandular epithelial clear cells. Various architectural patterns may be seen, including papillary, tubulocystic, and solid.
The presence of an follicular adenocarcinoma of the thyroid gland.
A thyroid neoplasm of mixed papillary and follicular arrangement. Its biological behavior and prognosis is the same as that of a papillary adenocarcinoma of the thyroid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1271)
A carcinoma that arises in a sebaseous gland (an exocrine gland of the skin that secretes sebum, a waxy substance.
A malignant glandular epithelial neoplasm consisting of secretory cells forming acinar patterns. Representative examples include the acinar cell carcinoma of the pancreas and the acinar adenocarcinoma of the prostate gland.
A malignant neoplasm of the ADRENAL CORTEX. Adrenocortical carcinomas are unencapsulated anaplastic (ANAPLASIA) masses sometimes exceeding 20 cm or 200 g. They are more likely to be functional than nonfunctional, and produce ADRENAL CORTEX HORMONES that may result in hypercortisolism (CUSHING SYNDROME); HYPERALDOSTERONISM; and/or VIRILISM.
An adenocarcinoma characterized by the presence of malignant glandular epithelial cells resembling endometrial cells. It can arise from the uterine body, ovary, fallopian tube, cervix, vagina, and uterine ligament.
An adenocarcinoma of the breast arising from the lobules. This is a relatively uncommon carcinoma, represents approximately 10% of the breast adenocarcinomas and is often bilateral or multifocal.
A term referring to medullary carcinomas which can develop in various anatomic sites such as the thyroid gland, breast, colon, rectum, and small intestine.
A carcinoma morphologically characterized the presence of cuboidal mucous cells, goblet-like mucous cells, squamoid cells, cystic changes, and a fibrotic stromal formation. It can occur in several anatomic sites, including parotid gland, oral cavity, paranasal sinus, skin, breast, lung, larynx, and lacrimal ducts. It is classified as low or high grade.
A malignant neuroendocrine neoplasm composed of cells containing secretory granules that stain positive for NSE and chromogranin. The neoplastic cells are often round and form clusters or trabecular sheets. Representative examples are small cell carcinoma, large cell neuroendocrine carcinoma, and Merkel cell carcinoma.
A usually aggressive, poorly differentiated invasive adenocarcinoma characterized by the presence of malignant glandular cells in which the nucleus is pressed to one side by the presence of intracytoplasmic mucus. It may arise from the stomach, small and large intestine, ampulla of Vater, appendix, gallbladder, pancreas, lung, bladder, breast, and prostate gland.
A carcinoma arising from the sebaceous glands, sweat glands, or the hair follicles. Representative examples include sebaceous carcinoma, apocrine carcinoma, eccrine carcinoma, and pilomatrical carcinoma.
A carcinoma that arises from the intrahepatic biliary tree (intrahepatic cholangiocarcinoma) or from the junction, or adjacent to the junction, of the right and left hepatic ducts (hilar cholangiocarcinoma). Grossly, the malignant lesions are solid, nodular, and grayish. Morphologically, the vast majority of cases are adenocarcinomas. Signs and symptoms include malaise, weight loss, right upper quadrant abdominal pain, and night sweats. Early detection is difficult and the prognosis is generally poor.
An invasive adenocarcinoma characterized by cystic changes and the presence of malignant glandular cells which contain intracytoplasmic mucin. It may arise from the ovary, pancreas, appendix, and lung.
A malignant cystic serous or mucinous epithelial neoplasm characterized by the presence of malignant glandular epithelial cells forming papillary structures. Stromal invasion is present.
A malignant cystic or semicystic neoplasm. It often occurs in the ovary and usually bilaterally. The external surface is usually covered with papillary excrescences. Microscopically, the papillary patterns are predominantly epithelial overgrowths with differentiated and undifferentiated papillary serous cystadenocarcinoma cells. Psammoma bodies may be present. The tumor generally adheres to surrounding structures and produces ascites. (From Hughes, Obstetric-Gynecologic Terminology, 1972, p185)
A cholangiocarcinoma that arises from the junction, or adjacent to the junction, of the right and left hepatic ducts.
A malignant epithelial neoplasm composed of giant, pleomorphic cells.
A malignant epithelial neoplasm composed of large, atypical cells.
A well differentiated squamous cell carcinoma characterized by a papillary growth pattern, acanthosis, mild cytologic atypia, and pushing tumor margins. The most commonly affected anatomic sites are the oral cavity, nasal cavity, larynx, esophagus, anus, vagina, vulva, and the plantar region of the foot.
Squamous or glandular intraepithelial neoplasia that affects the cervical mucosal epithelium. There is no evidence of stromal invasion. According to the degree of cellular atypia and the associated architectural changes, it is classified as low or high grade.
A serous neoplasm in which the cysts and papillae are lined by a single layer of cells without atypia, architectural complexity or invasion.
A neoplastic proliferation of basal cells in the epidermis (part of the skin) or other anatomic sites (most frequently the salivary glands). The basal cell neoplastic proliferation in the epidermis results in basal cell carcinomas. The basal cell neoplastic proliferation in the salivary glands can be benign, resulting in basal cell adenomas or malignant, resulting in basal cell adenocarcinomas.
Pilomatricoma, also known as pilomatrixoma, is a type of noncancerous (benign) skin tumor associated with hair follicles. Hair follicles are specialized structures in the skin where hair growth occurs. Pilomatricomas occur most often on the head or neck, although they can also be found on the arms, torso, or legs. A pilomatricoma feels like a small, hard lump under the skin. This type of tumor grows relatively slowly and usually does not cause pain or other symptoms. Most affected individuals have a single tumor, although rarely multiple pilomatricomas can occur. If a pilomatricoma is removed surgically, it tends not to grow back (recur).Most pilomatricomas occur in people under the age of 20. However, these tumors can also appear later in life. Almost all pilomatricomas are benign, but a very small percentage are cancerous (malignant). Unlike the benign form, the malignant version of this tumor (known as a pilomatrix carcinoma) occurs most often in middle age or late in life.Pilomatricoma usually occurs without other signs or symptoms (isolated), but this type of tumor has also rarely been reported with inherited conditions. Disorders that can be associated with pilomatricoma include Gardner syndrome, which is characterized by multiple growths (polyps) and cancers of the colon and rectum; myotonic dystrophy, which is a form of muscular dystrophy; and Rubinstein-Taybi syndrome, which is a condition that affects many parts of the body and is associated with an increased risk of both benign and malignant tumors.
A malignant epithelial tumor of glandular tissue, especially the salivary glands, characterized by acini with mucus-producing cells and by the presence of malignant squamous elements. Most mucoepidermoid tumors are low-grade lesions readily cured by adequate excision. They may appear in any age group. They grow slowly. If high-grade, they behave aggressively, widely infiltrating the salivary gland and producing lymph node and distant metastases. (Dorland, 27th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575)
An intraluminal papillary epithelial neoplasm arising within the ducts. Representative examples are the intraductal breast papilloma and the salivary gland intraductal papilloma.
A neoplasm composed of neural epithelium, not necessarily a neoplasm located in the neural epithelium or neuroepithelium.
A well differentiated, slow growing neuroepithelial neoplasm composed of neoplastic, mature ganglion cells and neoplastic glial cells. Some gangliogliomas show anaplastic features in their glial component and are considered to be WHO grade III. Rare cases of newly diagnosed gangliogliomas with grade IV (glioblastoma) changes in the glial component have also been reported. (Adapted from WHO)
A malignant olfactory neuroblastoma arising from the olfactory epithelium of the superior nasal cavity and cribriform plate.
A moderately malignant neoplasm composed of primitive neuroectodermal cells dispersed in myxomatous or fibrous stroma intermixed with mature ganglion cells. It may undergo transformation into a neuroblastoma. It arises from the sympathetic trunk or less frequently from the adrenal medulla, cerebral cortex, and other locations. Cervical ganglioneuroblastomas may be associated with HORNER SYNDROME and the tumor may occasionally secrete vasoactive intestinal peptide, resulting in chronic diarrhea.
An intraventricular neuronal neoplasm composed of uniform round cells with neuronal differentiation. It is typically located in the lateral ventricles in the region of the foramen of Monro. It generally affects young adults and has a favorable prognosis. (Adapted from WHO)
A neoplasm that is composed of squamous epithelial cells. Squamous cell carcinoma is a representative example.
An endophytic benign papillary epithelial neoplasm that results from the invagination and proliferation of epithelial cells in the underlying stroma. Representative examples are the inverted urothelial papilloma that arises from the urinary tract and inverted Schneiderian papilloma that arises from the nasal cavity or paranasal sinuses.
Neoplasms composed of tissues of the OVARY or the TESTIS, not neoplasms located in the ovaries or testes. Gonadal tissues include GERM CELLS, cells from the sex cord, and gonadal stromal cells.
A sex cord-gonadal stromal tumor consists of LEYDIG CELLS; SERTOLI CELLS; and FIBROBLASTS in varying proportions and degree of differentiation. Most such tumors produce ANDROGENS in the Leydig cells, formerly known as androblastoma or arrhenoblastoma. Androblastomas occur in the TESTIS or the OVARY causing precocious masculinization in the males, and defeminization, or virilization (VIRILISM) in the females. In some cases, the Sertoli cells produce ESTROGENS.
A neoplasm arising in the ovary or testis. It is composed of granulosa cells, Leydig cells, Sertoli cells, and fibroblasts. Each of these cell types may constitute the only cellular component that is present in the neoplasm or it may be mixed with other cell types in various combinations. The prognosis can not always be predicted on histologic grounds alone. Approximately, 10% of these tumors may metastasize. Representative examples include granulosa cell tumor, Leydig cell tumor, Sertoli cell tumor, and tumors of the thecoma-fibroma group.
A benign, slow growing neoplasm which is typically attached to a ventricular wall. It is composed of glial tumor cell clusters embedded in an abundant fibrillary matrix with frequent microcystic change. Some lesions have the histological features of both subependymoma and ependymoma. It is often detected incidentally and has a very favorable prognosis. (Adapted from WHO.)
A rare histological variant of glioblastoma (WHO grade IV) characterized by a biphasic tissue pattern with alternating areas displaying glial and mesenchymal differentiation (WHO).
A benign or malignant neoplasm arising from the perineural cells in the sheaths surrounding the nerves. Representative examples include neurofibroma, schwannoma, and malignant peripheral nerve sheath tumor.
A neurofibroma in which Schwann cells proliferate inside the nerve sheath, producing an irregularly thickened, distorted, tortuous structure.
A form of malignant cancer of the connective tissue surrounding nerves. Given its origin and behavior, it is classified as a sarcoma.
A benign neoplasm arising from nerve sheaths. It is characterized by the presence of a myxoid stroma.
A benign neoplasm of fibrous tissue in which there are numerous small and large, frequently dilated, vascular channels. (Stedman, 25th ed)
A low-grade malignant blood vessel neoplasm. It is characterized by the presence of epithelioid endothelial cells. The neoplastic cells are arranged in cords and nests, which are embedded in a myxoid to hyalinized stroma.
A common hemangioma characterized by the presence of capillary-sized vascular channels without prominent epithelioid endothelial cells.
A WHO grade I tumor of uncertain histogenesis which is composed of stromal cells and abundant capillaries. Approximately 25% of hemangioblastomas are associated with Von Hippel-Lindau disease, a disease inherited through an autosomal dominant trait and characterized by the development of hemangioblastomas of the central nervous system and retina, clear cell renal carcinoma, pheochromocytoma, and pancreatic and inner ear tumors. (Adapted from WHO)
A melanoma characterized by the complete absence of melanin pigment in the melanoma cells. It occurs more frequently on the face and it is often associated with desmoplastic reaction.
An intradermal nevus characterized by the presence of benign pigmented dendritic spindle-shaped melanocytes. It most frequently occurs in the skin of the distal upper extremities, followed by the lower extremities, scalp, face, and buttocks. It usually presents as a single blue or blue-black papular lesion less than 1cm in diameter. Simple excision is usually curative.
A nevus characterized by the proliferation of nevus cells in the dermis without involvement of the dermal-epidermal junction.
A nevus characterized by the presence of spindle-shaped melanocytes.
A benign, acquired or congenital, usually single skin lesion. It can occur on any area of the body, but most commonly occurs on the face of children and the thighs of young females. It is characterized by a proliferation of large spindle, oval, or large epithelioid melanocytes in the dermal-epidermal junction. The melanocytic proliferation subsequently extends into the dermis.
A benign, intraosseous or extraosseous cystic neoplasm arising from tooth-forming tissues. It is characterized by the presence of a cyst lined by an ameloblastoma-like epithelium and ghost cells formation. The ghost cells may undergo calcification. It is treated with enucleation. Few recurrences have been reported for intraosseous neoplasms whereas no recurrences have been reported for extraosseous neoplasms.
A rare but highly lethal childhood tumor found almost exclusively in infants. Histopathologically, it resembles RHABDOMYOSARCOMA but the tumor cells are not of myogenic origin. Although it arises primarily in the kidney, it may be found in other parts of the body. The rhabdoid cytomorphology is believed to be the expression of a very primitive malignant cell. (From Holland et al., Cancer Medicine, 3d ed, p2210)
A rare immunodeficiency syndrome characterized by the decrease of the CD4-positive lymphocytes below 300 per cubic millimeter in the absence of identifiable immunodeficiency causes. Patients with this syndrome are at an increased risk of opportunistic infections.
Virus diseases caused by the HEPADNAVIRIDAE.
Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).
Virus diseases caused by RHABDOVIRIDAE. Important infections include RABIES; EPHEMERAL FEVER; and vesicular stomatitis.
Virus diseases caused by members of the ALPHAVIRUS genus of the family TOGAVIRIDAE.
Virus diseases caused by the RUBIVIRUS genus, of the family TOGAVIRIDAE.
A benign or malignant neoplasm composed of cells of neuroendocrine origin. Representative examples include paraganglioma, carcinoid tumor, and neuroendocrine carcinoma.
Congenital structural deformities of the upper and lower extremities collectively or unspecified.
Neoplasms composed of more than one type of neoplastic tissue.
A benign, intermediate, or malignant neoplasm that affects the connective and soft tissue.
Neoplasms composed of sebaceous or sweat gland tissue or tissue of other skin appendages. The concept does not refer to neoplasms located in the sebaceous or sweat glands or in the other skin appendages.
Neoplasms containing cyst-like formations or producing mucin or serum.
Neoplasms, usually carcinoma, located within the center of an organ or within small lobes, and in the case of the breast, intraductally. The emphasis of the name is on the location of the neoplastic tissue rather than on its histological type. Most cancers of this type are located in the breast.
A collective term for the various types of nevi and melanomas.
A nucleoside reverse transcriptase inhibitor analog of thymidine.
A cyclic cytidine.Cifostodine is formed during digestion of ribonucleic acid by ribonuclease.
A hydrazone derivative of isoniazid, used in the treatment and prophylaxis of tuberculosis.
A synthetic thymidine analogue with potent antiviral activity against herpes simplex and varicella zoster viruses. Sorivudine is phosphorylated into triphosphate form within the cells; this metabolite interferes with viral DNA replication by inhibiting DNA polymerase activity without been incorporated into elongating viral DNA. Due to the dangerous effects of drug-drug interactions via its metabolite, sorivudine has been removed from the market.
A naturally occurring monoterpene related to limonene with antineoplastic activity. Perillyl alcohol inhibits farnesyl transferase and geranylgeranyl transferase, thereby preventing post-translational protein farnesylation and isoprenylation and activation of oncoproteins such as p21-ras, and arresting tumor cells in the G1 phase of the cell cycle. (NCI04)
A macrocyclic antifungal antibiotic that inhibits signal-dependent transcriptional activation and induces differentiation in leukemia. (NCI)
A broad-spectrum parenteral carbapenem with activity against aerobic, anaerobic, gram-positive and gram-negative organisms including non-fermenters. Panipenem is often co-administered with betamipron to prevent nephrotoxicity.
A nucleoside analog of uridine with activity against hepatitis B virus and herpes viruses. Fialuridine inhibits viral DNA polymerase and viral replication.
A butyrophenone that has been investigated for antineoplastic activity. (NCI04)
A benzotriazine di-N-oxide with potential antineoplastic activity. Tirapazamine is selectively activated by multiple reductases to form free radicals in hypoxic cells, thereby inducing single-and double-strand breaks in DNA, base damage, and cell death. This agent also sensitizes hypoxic cells to ionizing radiation and inhibits the repair of radiation-induced DNA strand breaks via inhibition of topoisomerase II. (NCI04)
A specific HLA-B surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-B*39 allele family.
Dexniguldipine is the (+)-enantiomer of the dihydropyridine derivate niguldipine. Dexniguldipine showed a binding affinity to the P-glycoprotein and therefore it is to be assumed to block the P-glycoprotein pumping mechanism and to modulate multidrug resistance. (NCI)
A non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Moexiprilat competitively inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the actions of the potent vasoconstrictor angiotensin II and leads to vasodilatation. This agent also prevents angiotensin II-induced aldosterone secretion by the adrenal cortex, thereby promoting diuresis and natriuresis.
An indole derivative and a potent serotonin 5-HT3 receptor antagonist with anti-emetic property. Dolasetron blocks the activity of serotonin released from the enterochromaffin cells of the small intestine by selectively inhibiting and inactivating 5-HT3 receptors located on the nerve terminals of the vagus nerve in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. This results in suppression of signalling to trigger chemo- and radiotherapy induced nausea and vomiting.
A synthetic cyclic octapeptide analogue of somatostatin. Lanreotide binds to somatostatin receptors (SSTR), specifically SSTR-2 and also to SSTR-5 with a lesser affinity. However, compare with octreotide, this agent is less potent in inhibiting the release of growth hormone from the pituitary gland. Furthermore, lanreotide has an acute effect on decreasing circulating total and free insulin-like growth factor 1 (IGF-I). This agent is usually given as a prolonged-release microparticle or Autogel formulation for the treatment of acromegaly and to relieve the symptoms of neuroendocrine tumors.
A diacetyl 6-deoxy prodrug analog of the antiviral agent penciclovir. Orally administered, famciclovir in vivo is converted to penciclovir triphosphate, which is active against the Herpes viruses, including herpes simplex 1 and 2 and varicella-zoster. This agent inhibits the replication of viral DNA by interfering competitively with DNA polymerase. (NCI04)
An androstanol non-depolarizing neuromuscular blocking agent. It has a mono-quarternary structure and is a weaker nicotinic antagonist than PANCURONIUM.
Cetrorelix is a synthetic decapeptide which is structurally related to gonadotrophin-releasing hormone (luteinising-hormone releasing hormone). It acts as an LHRH antagonist. (from ASTA Medica)
The morpholinoethyl ester of mycophenolic acid (MPA) with potent immunosuppressive properties. Mycophenolate stops T-cell and B-cell proliferation through selective inhibition of the de novo pathway of purine biosynthesis. In vivo, the active metabolite, MPA, reversibly inhibits inosine 5'-monophosphate dehydrogenase, an enzyme involved in the de novo synthesis of guanine nucleotides. MPA displays high lymphocyte specificity and cytotoxicity due to the higher dependence of activated lymphocytes on both salvage and de novo synthesis of guanine nucleotides relative to other cell types. (NCI04)
A gadolinium-based paramagnetic contrast agent. When placed in a magnetic field, gadobenate dimeglumine produces a large magnetic moment and so a large local magnetic field, which can enhance the relaxation rate of nearby protons; as a result, the signal intensity of tissue images observed with magnetic resonance imaging (MRI) may be enhanced. Because this agent is preferentially taken up by normal functioning hepatocytes, normal hepatic tissue is enhanced with MRI while tumor tissue is unenhanced. In addition, because gadobenate dimeglumine is excreted in the bile, it may be used to visualize the biliary system using MRI.
A guanine ribonucleotide derivative with immunostimulatory and immunomodulatory activity. Loxoribine undergoes facilitated transport across the plasma membrane into the cytoplasmic compartment of the cell and acts intracellularly, bypassing the biochemical steps involved in the membrane signal transduction pathway used by Ag or anti-IgM Abs to activate B cells. This agent activates the Toll-like receptor 7 (TLR7), a member of the TLR family of pathogen-associated molecular pattern recognition receptors thereby activating the innate immune system. This activation requires endosomal maturation and recognition is restricted to TLR7. As a result, loxoribine induces cycling B cells to proliferate and differentiate non-specifically and recruit antigen-reactive B cells to undergo differentiation to antibody production, markedly amplifying the underlying response in the process.
A reverse transcriptase inhibitor and ZALCITABINE analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease.
A synthetic cyclopropylpyrroloindole antineoplastic antibiotic. Bizelesin binds to the minor groove of DNA and induces interstrand cross-linking of DNA, thereby inhibiting DNA replication and RNA synthesis. Bizelesin also enhances p53 and p21 induction and triggers G2/M cell-cycle arrest, resulting in cell senescence without apoptosis. (NCI04)
A recombinant form of CD4 antigen with anti-HIV application. Recombinant soluble T4 antigen (rsT4) is derived from cell surface antigen CD4 lacking its transmembrane and cytoplasmic domains, thereby the agent is mobile within tissues. rsT4 binds to the envelope glycoprotein gp110 of HIV and prevents the binding of virus to CD4 positive lymphocytes, resulting in an inhibition of virus infectivity.
A non-nucleoside reverse transcriptase inhibitor. Atevirdine is active against AZT-resistant virus strains.
A mesylate salt form of atevirdine, a non-nucleoside reverse transcriptase inhibitor. Atevirdine is active against AZT-resistant virus strains.
A synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity. Triapine inhibits the enzyme ribonucleotide reductase, resulting in the inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleotides necessary for DNA synthesis. This agent has been shown to inhibit tumor growth in vitro. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37830&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=37830&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2242"" NCI Thesaurus)
A member of the family of tissue inhibitor of metalloproteinases. Mutations of the gene for TIMP3 PROTEIN causes Sorsby fundus dystrophy.
A recombinant granulocyte colony-stimulating factor (G-CSF) that is used in the treatment and prevention of NEUTROPENIA, preparation and collection of blood progenitor cells, and for use in PERIPHERAL BLOOD STEM CELL TRANSPLANTATION.
A guanine-derived ANTINEOPLASTIC AGENT that functions as a NUCLEIC ACID SYNTHESIS INHIBITOR through its binding to, and inhibition of, THYMIDYLATE SYNTHASE.
A synthetic, nonopiod, twenty-five amino acid polybasic peptide analogue of an omega-conotoxin derived from the marine snail Conus magus with analgesic activity. Ziconotide appears to block neuronal N-type voltage-sensitive calcium channels (NCCB), inhibiting transmission from pain-sensing primary nociceptors. This agent may exhibit significant analgesic activity in refractory pain.
A purified, natural saponin isolated from the soapbark tree Quillaja saponaria Molina with potential immunoadjuvant activity. When co-administered with vaccine peptides, QS21 may increase total antitumoral vaccine-specific antibody responses and cytotoxic T-cell responses.
A derivative of the Canarypox Virus, ALVAC can infect mammalian cells but it can't replicate. Thus, it produces a self-limiting infection which does not produce symptoms or harm the host. When carrying foreign genes it will cause transient expression of protein.
An alkaloid phytochemical found in the Morinda Citrifolia (Noni) that inhibits the growth of RAS cancer cells. The exact mechanism is unknown but may involve the inhibition of tyrosine kinase. (NCI)
The oil extracted from the seeds of Borago officinalis. Borage oil has anti-inflammatory properties and is used in skincare preparations.
An orally-administered oil composed of the monounsaturated fatty acids glyceryl trioleate (GTO), the triacylglycerol form of oleic acid derived from olive oil, and glyceryl trierucate (GTE), the triacylglycerol form of erucic acid derived from rapeseed oil, in a 4:1 ratio, that can be used in the treatment of adrenoleukodystrophy (ALD). Upon oral administration of Lorenzo's oil, the monounsaturated fatty acids compete with saturated fatty acids as substrates for enzymes in the elongation of very long-chain fatty acids (ELOVL) family. This results in the elongation and production of monounsaturated very long-chain fatty acids (VLCFAs) and reduces the elongation of saturated VLCFAs. This reduces the plasma levels of saturated VLCFAs and prevents their accumulation in the brain, thereby preventing demyelination of cerebral nerves and halting the progression of ALD.
A quinolinone sulfooxime and inhibitor of Na-K-Cl cotransporters 1 and 2 with diuretic activity.
A member of the tyrphostin family of tyrosine kinase inhibitors that competitively binds and inhibits epidermal growth factor receptor and GTPase activity of transducin and induces apoptosis in human leukemic cell lines. (NCI)
A semisynthetic agent related to camptothecin with potent antitumor and antiviral properties. Rubitecan binds to and inhibits the enzyme topoisomerase I and induces protein-linked DNA single-strand breaks, thereby blocking DNA and RNA synthesis in dividing cells; this agent also prevents repair of reversible single-strand DNA breaks. (NCI04)
A recombinant form of a mature, N-terminal secretory peptide derived from a parathyroid hormone-related protein (PTHrP) preprohormone through posttranslational endoproteolytic processing with vasodilating, myorelaxant, and parathyroid hormone (PTH)-like calciotropic activities. Expressed throughout the cardiovascular system, parathyroid hormone-related protein (1-36) [PTHrP (1-36)] was first identified as the PTH-like hypercalcemic factor of humoral hypercalcemia of malignancy; however, its sequence differs significantly from that of PTH (1-34) although both proteins share the same N-terminal end which accounts for the calciotropic activity. Both PTHrP (1-36) and PTH (1-34) bind to the type 1 parathyroid hormone receptor (PTH1R), a specific seven-transmembrane-helix-containing G protein-coupled receptor mainly located in bone and kidney cells.
A compound that inhibits calmodulin kinase II and p60. (NCI)
A water-insoluble camptothecin derivative. Aminocamptothecin binds to the nuclear enzyme topoisomerase I, thereby inhibiting repair of single-strand DNA breakages. Because the terminal lactone ring of aminocamptothecin required for the agent's antitumor activity spontaneously opens under physiological conditions to an inactive carboxy form, the drug must be administered over an extended period of time to achieve effective cytotoxicity. (NCI04)
A lipophilic, anthracycline antineoplastic antibiotic. Annamycin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and repair as well as inhibiting RNA and protein synthesis. This agent appears to not be a substrate for the p-glycoprotein associated multidrug-resistance (MDR) transporter; therefore, overcoming the resistance pattern seen with other anthracycline compounds.
DTP-Haemophilus influenzae type b conjugate vaccine.
A synthetic hydroxamate with potential antineoplastic activity. Batimastat binds covalently to the zinc ion in the active site of matrix metalloproteinases (MMPs), thereby inhibiting the action of MMPs, inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. (NCI04)
ADM (185 aa, ~20 kDa) is encoded by the human ADM gene. This protein plays a role in both signal transduction and vasodilation.
A compound that selectively inhibits protein tyrosine kinase and nerve growth factor-dependent tyrosine phosphorylation. (NCI)
Essential oil extracted from MELALEUCA ALTERNIFOLIA (tea tree). It is used as a topical antimicrobial due to the presence of terpineol.
A recombinant therapeutic agent chemically identical to endogenous human GM-CSF except a leucine substitution in position 23. Binding to specific cell surface receptors, sargramostim modulates the proliferation and differentiation of a variety of hematopoietic progenitor cells with some specificity towards stimulation of leukocyte production and may reverse treatment-induced neutropenias. This agent also promotes antigen presentation, up-regulates antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function; it may also augment host antitumoral immunity.
A low-molecular-weight heparin with anticoagulant properties that is used in the prevention and treatment of VENOUS THROMBOEMBOLISM, and to prevent clotting during EXTRACORPOREAL CIRCULATION.
A guanido-neuraminic acid that is used to inhibit NEURAMINIDASE.
A tetrazole derivative and ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKER that is used to treat HYPERTENSION.
A lung surfactant agent that is used as a replacement for endogenous lung surfactant. Colfosceril palmitate is effective in reducing the surface tension of pulmonary fluids, thereby increasing lung compliance properties to prevent alveolar collapse and improve breathing. This drug is used in the treatment of neonatal respiratory distress.
A pyrrolidone non-competitive inhibitor of hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase. Crilvastatin acts by stimulating LDL-cholesterol uptake by hepatocytes and also by stimulating bile cholesterol and bile salt secretion.
A benzopyridoindole derivative with antineoplastic property. Intoplicine inhibits activities of both topoisomerase I and II via intercalating DNA helix, thereby hindering the movements of enzymes along DNA molecules during DNA transcription and replication, respectively. Furthermore, this agent stabilizes DNA-enzyme complexes during unwinding processes by both topoisomerases, leading to double- and single-stranded DNA breaks. Consequently, these effects bring about cell growth inhibition and apoptosis of tumor cells.
An orally bioavailable substituted benzamide derivative with potential antineoplastic activity. Tacedinaline inhibits histone deacetylation, which may result in histone hyperacetylation, followed by the induction of differentiation, the inhibition of cell proliferation, and apoptosis in susceptible tumor cell populations.
A bone-seeking chelating agent. Has been used as a radiopharmaceutical in complexes with radioactive metals for bone marrow ablation.
A substance being studied in the treatment of cancer. It inhibits a hormone growth factor that causes some cancer cells to divide. It is a type of vasopressin receptor antagonist.
A synthetic imidazole that inhibits hepatic cholesterol biosynthesis by inhibiting the cytochrome P450 enzyme lanosterol 14alpha-demethylase. In an animal model, Azalanstat lowered serum cholesterol in a dose-depended manner.
A glycosylated form of a recombinant therapeutic agent which is chemically identical to or similar to an endogenous human granulocyte colony-stimulating factor (G-CSF). Produced endogenously by monocytes, fibroblasts, and endothelial cells, G-CSF binds to and activates specific cell surface receptors, stimulating neutrophil progenitor proliferation and differentiation and selected neutrophil functions.
A recombinant analog of the endogenous cytokine interleukin-2 (IL-2) with immunoregulatory and antineoplastic activities. Aldesleukin binds to and activates the IL-2 receptor, followed by heterodimerization of the cytoplasmic domains of the IL-2R beta and gamma(c) chains; activation of the tyrosine kinase Jak3; and phosphorylation of tyrosine residues on the IL-2R beta chain, resulting in an activated receptor complex. Various cytoplasmic signaling molecules are recruited to the activated receptor complex and become substrates for regulatory enzymes that are associated with the receptor complex. This agent enhances lymphocyte mitogenesis; stimulates long-term growth of human IL-2 dependent cell lines; enhances lymphocyte cytotoxicity; induces lymphokine-activated killer (LAK) cell and natural killer (NK) cell activities; and induces expression of interferon-gamma. Aldesleukin may induce T cell-mediated tumor regression in some tumor types.
Isoquinoline and quinuclidine derivative that acts as a 5-HT3 RECEPTOR antagonist. It is used in the prevention of nausea and vomiting induced by cytotoxic chemotherapy, and for the prevention of post-operative nausea and vomiting.
A benign or malignant, primary or metastatic neoplasm of the brain occurring in children.
Non-Hodgkin lymphoma occurring in adults.
An aggressive malignant mesenchymal neoplasm arising from skeletal muscle in children. Only a small percentage of tumors arise in the skeletal muscle of the extremities. The majority arise in other anatomical sites.
Non-Hodgkin lymphoma occurring in childhood.
Soft tissue sarcoma occurring in adults.
An acute myeloid leukemia occurring in adults.
A benign or malignant neoplasm that affects the Bartholin gland. Representative examples include adenoma, adenomyoma, adenocarcinoma, and squamous cell carcinoma.
A usually small, slow-growing, well differentiated neuroendocrine tumor arising from the digestive system. It is composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with small vesicular nuclei. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent. The tumor can occur anywhere in the digestive system; approximately 90% arise in the appendix.
Acute myeloid leukemia occurring in childhood.
A benign or malignant, primary or metastatic neoplasm of the brain occurring in adults.
A hepatocellular carcinoma or intrahepatic cholangiocarcinoma that occurs during adulthood.
A malignant melanoma originating within the eye. The tumor originates from the melanocytes in the uvea (which comprises the iris, ciliary body, and choroid).
A squamous cell carcinoma that has metastasized to the neck region from an unknown primary anatomic site.
A primary or metastatic malignant neoplasm that affects the major or minor salivary glands. Representative examples include carcinoma, lymphoma, and sarcoma.
A carcinoma arising in the lip or oral cavity. Most oral cavity carcinomas are squamous cell carcinomas of the tongue, buccal mucosa, or gums. Less frequent morphologic variants include mucoepidermoid carcinoma and adenocarcinoma. Lip carcinomas are usually basal cell or squamous cell carcinomas.
Hodgkin lymphoma occurring in childhood.
Soft tissue sarcoma occurring in childhood.
A carcinoma which has metastasized from an unknown primary anatomic site.
A transitional cell carcinoma that arises from the renal pelvis and ureter.
A malignant neoplasm that has spread to the brain from another anatomic site or system. The majority are carcinomas (usually lung or breast carcinomas).
Diffuse spread of cancer to the meninges.
Presence of fluid in the pericardial space as a complication of malignant disease.
Accumulation of fluid in the peritoneal cavity resulting from the growth of primary or metastatic malignant neoplasms in the peritoneum.
An autosomal dominant inherited type of acrocephalosyndactyly caused by mutations in the FGFR1 or FGFR2 genes. It is characterized by early closure of the sutures between the skull bones, bulging and wide-set eyes, broad thumbs, big toes, and partial syndactyly in the hands and toes.
A syndrome of short hands and feet, nasal hypoplasia, mental retardation, and characteristic facies.
Distal arthrogryposis type 1 is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The term ""arthrogryposis"" comes from the Greek words for joint (arthro-) and crooked or hooked (gryposis). The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). Clubfoot, which is an inward- and upward-turning foot, is also commonly seen with distal arthrogryposis type 1. The specific hand and foot abnormalities vary among affected individuals. However, this condition typically does not cause any signs and symptoms affecting other parts of the body.
Blephariphimosis, ptosis, and epicanthus inversus syndrome (BPES) is a complex eyelid malformation invariably characterized by four major features: blepharophimosis, ptosis, epicanthus inversus, and telecanthus. BPES type I includes the four major features and premature ovarian insufficiency (POI); BPES type II includes only the four major features. Other ophthalmic manifestations that can be associated with BPES include lacrimal duct anomalies, amblyopia, strabismus, and refractive errors. Minor features include a broad nasal bridge, low-set ears, and a short philtrum. Individuals with BPES and an intragenic FOXL2 pathogenic variant are expected to have normal intelligence, in contrast to affected individuals with cytogenetic rearrangements that involve FOXL2 and additional genes.
This type of brachydactyly is characterized by short and broad terminal phalanges of the thumbs and big toes.
DA3, or Gordon syndrome, is distinguished from other distal arthrogryposes by short stature and cleft palate (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA3 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 5 (DA5; 108145) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of ocular abnormalities and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders may represent variable expressivity of the same condition. For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Congenital contractural arachnodactyly (CCA) is characterized by a Marfan-like appearance (tall, slender habitus in which arm span exceeds height) and long, slender fingers and toes (arachnodactyly). Most affected individuals have ""crumpled"" ears that present as a folded upper helix of the external ear and most have contractures of major joints (knees and ankles) at birth. The proximal interphalangeal joints also have flexion contractures (i.e., camptodactyly), as do the toes. Hip contractures, adducted thumbs, and clubfoot may occur. The majority of affected individuals have muscular hypoplasia. Contractures usually improve with time. Kyphosis/scoliosis is present in about half of all affected individuals. It begins as early as infancy, is progressive, and causes the greatest morbidity in CCA. Dilatation of the aorta is occasionally present. Infants have been observed with a severe/lethal form characterized by multiple cardiovascular and gastrointestinal anomalies in addition to the typical skeletal findings.
A rare branchial arches and limb primordia development disorder with characteristics of variable degrees of uni or bilateral craniofacial malformation and radial defects that result in extremely variable phenotypic manifestations. Characteristic features include low postnatal weight, short stature, vertebral defects, hearing loss, and facial dysmorphism (including facial asymmetry, external, middle and inner ear malformations, orofacial clefts, and mandibular hypoplasia). These features are invariably associated with radial defects, such as preaxial polydactyly, thumb and/or radius hypoplasia/agenesis, or triphalangeal thumb. Cardiac, pulmonary, renal, and central nervous system involvement has also been reported.
Achondrogenesis type II is characterized by severe micromelic dwarfism with small chest and prominent abdomen, incomplete ossification of the vertebral bodies, and disorganization of the costochondral junction. This form is an autosomal dominant trait occurring mostly as new mutations. However, somatic and germline mosaicism have been reported (summary by Comstock et al., 2010).
A very rare genetic disorder with characteristics of the following congenital malformations: hydrocephalus (due to Dandy-Walker anomaly), cleft palate and severe joint contractures. Less than 20 cases have been reported in the literature. The fingers are thin with absent knuckles and reduced creases over the joints and patients show an inability to make a full fist. Additional findings may include deformed ears, ptosis, an inability to open the mouth fully, heart defects, and clubfoot. There are currently no human genes associated with this disease.
KBG syndrome is typically characterized by macrodontia (especially of the upper central incisors), characteristic facial features (triangular face, brachycephaly, synophrys, widely spaced eyes, broad or bushy eyebrows, prominent ears, prominent nasal bridge, bulbous nose, anteverted nares, long philtrum, and thin vermilion of the upper lip), short stature, developmental delay / intellectual disability, and behavioral issues. Affected individuals may have feeding difficulties (particularly in infancy), skeletal anomalies (brachydactyly, large anterior fontanelle with delayed closure, scoliosis), hearing loss (conductive, mixed, and sensorineural), seizure disorder, and brain malformations. There is significant variability in the clinical findings, even between affected members of the same family.
A benign form of macrocephaly, sometimes identified with Sotos syndrome, with normal or near-normal birth weight and length with subsequent obesity, variable developmental delay, and typical square facies with frontal bossing, dished-out midface, biparietal narrowing, and long philtrum.
A rare developmental anomaly, affecting primarily the anterior part of the maxilla and nasal complex. Affected individuals typically have an unusually flat, underdeveloped midface, with an abnormally short nose and flat nasal bridge, underdeveloped upper jaw, relatively protruding lower jaw and/or a 'reverse overbite'' (or class III malocclusion). Hypoplasia of distal phalanges of fingers was reported in some cases. The pathogenesis remains uncertain, most reported cases were sporadic.
Microcephaly strictly means abnormally small head size, but usually refers to an occipitofrontal head circumference below -2 SD from the mean for the infant's gestational age, sex, and ethnic origin. Microcephaly may appear as an isolated trait or in association with other malformations. It may also be sporadic or familial. Some familial cases are autosomal dominant, but most appear to be recessive (see 251200) (summary by Merlob et al., 1988).
A form of polydactyly in which the extra digit or digits are localized on the side of the fifth finger or fifth toe.
Medium-chain acyl-coenzyme A dehydrogenase (MCAD) is one of the enzymes involved in mitochondrial fatty acid ß-oxidation, which fuels hepatic ketogenesis, a major source of energy once hepatic glycogen stores become depleted during prolonged fasting and periods of higher energy demands. In a typical clinical scenario, a previously healthy child with MCAD deficiency presents with hypoketotic hypoglycemia, vomiting, and lethargy triggered by a common illness. Seizures may occur. Hepatomegaly and liver disease are often present during an acute episode, which can quickly progress to coma and death. Children are normal at birth and – if not identified through newborn screening – typically present between ages three and 24 months; later presentation, even into adulthood, is possible. The prognosis is excellent once the diagnosis is established and frequent feedings are instituted to avoid any prolonged period of fasting.
A genetic disorder characterized by deficiency of the enzyme long-chain acyl-coenzyme A dehydrogenase that metabolizes long-chain fatty acids. Signs and symptoms appear in infancy or childhood and may be triggered during fasting, illness or exercise. They include hypoglycemia, muscle weakness and lethargy.
Cerebrooculofacioskeletal syndrome is an autosomal recessive progressive neurodegenerative disorder characterized by microcephaly, congenital cataracts, severe mental retardation, facial dysmorphism, and arthrogryposis (summary by Jaakkola et al., 2010). Genetic Heterogeneity of Cerebrooculofacioskeletal Syndrome See also COFS2 (610756), caused by mutation in the ERCC2 gene (126340); COFS3 (616570), caused by mutation in the ERCC5 gene (133530); and COFS4 (610758), caused by mutation in the ERCC1 gene (126380).
Absence or abnormal closure of the posterior portion of the choana (the posterior nasal aperture).
Diastrophic dysplasia (DTD) is characterized by limb shortening, normal-sized skull, hitchhiker thumbs, spinal deformities (scoliosis, exaggerated lumbar lordosis, cervical kyphosis), and contractures of the large joints with deformities and early-onset osteoarthritis. Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. On occasion the disease can be lethal at birth, but most affected individuals survive the neonatal period and develop physical limitations with normal intelligence.
Fryns syndrome is characterized by diaphragmatic defects (diaphragmatic hernia, eventration, hypoplasia or agenesis); characteristic facial appearance (coarse facies, ocular hypertelorism, broad and flat nasal bridge, thick nasal tip, long philtrum, low-set and poorly formed ears, tented upper lip, macrostomia, micrognathia); distal digital hypoplasia (nails, terminal phalanges); pulmonary hypoplasia; and associated anomalies (polyhydramnios, cloudy corneas and/or microphthalmia, orofacial clefting, renal dysplasia/renal cortical cysts, and/or malformations involving the brain, cardiovascular system, gastrointestinal system, genitalia). Survival beyond the neonatal period has been rare. Data on postnatal growth and psychomotor development are limited; however, severe developmental delay and intellectual disability are common.
A very rare syndrome with characteristics of the combination of hypertelorism, cleft lip and palate and microtia. Nine cases have been reported in the literature in seven families. Some patients have associated cardiac or renal congenital malformations. Short stature and intellectual deficiency are common. The reported cases support autosomal recessive inheritance.
Gastrointestinal defects and immunodeficiency syndrome (GIDID) is characterized by multiple intestinal atresia, in which atresia occurs at various levels throughout the small and large intestines. Surgical outcomes are poor, and the condition is usually fatal within the first month of life. Some patients exhibit inflammatory bowel disease (IBD), with or without intestinal atresia, and in some cases, the intestinal features are associated with either mild or severe combined immunodeficiency (Samuels et al., 2013; Avitzur et al., 2014; Lemoine et al., 2014).
The cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD) spectrum disorders are a continuum that includes the following phenotypes: Metaphyseal dysplasia without hypotrichosis (MDWH). Cartilage-hair hypoplasia (CHH). Anauxetic dysplasia (AD). CHH-AD spectrum disorders are characterized by severe disproportionate (short-limb) short stature that is usually recognized in the newborn, and occasionally prenatally because of the short extremities. Other findings include joint hypermobility, fine silky hair, immunodeficiency, anemia, increased risk for malignancy, gastrointestinal dysfunction, and impaired spermatogenesis. The most severe phenotype, AD, has the most pronounced skeletal phenotype, may be associated with atlantoaxial subluxation in the newborn, and may include cognitive deficiency. The clinical manifestations of the CHH-AD spectrum disorders are variable, even within the same family.
If untreated, young children with profound biotinidase deficiency usually exhibit neurologic abnormalities including seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, and cutaneous abnormalities (e.g., alopecia, skin rash, candidiasis). Older children and adolescents with profound biotinidase deficiency often exhibit motor limb weakness, spastic paresis, and decreased visual acuity. Once vision problems, hearing loss, and developmental delay occur, they are usually irreversible, even with biotin therapy. Individuals with partial biotinidase deficiency may have hypotonia, skin rash, and hair loss, particularly during times of stress.
Niemann-Pick disease type C (NPC) is a lipid storage disease that can present in infants, children, or adults. Neonates can present with ascites and severe liver disease from infiltration of the liver and/or respiratory failure from infiltration of the lungs. Other infants, without liver or pulmonary disease, have hypotonia and developmental delay. The classic presentation occurs in mid-to-late childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy (VSGP), and dementia. Dystonia and seizures are common. Dysarthria and dysphagia eventually become disabling, making oral feeding impossible; death usually occurs in the late second or third decade from aspiration pneumonia. Adults are more likely to present with dementia or psychiatric symptoms.
A rare genetic disorder that affects the adrenal gland. It usually presents in infancy with signs and symptoms of adrenal insufficiency. If it is not recognized and treated promptly, it may be lethal.
Craniofrontonasal syndrome is an X-linked developmental disorder that shows paradoxically greater severity in heterozygous females than in hemizygous males. Females have frontonasal dysplasia, craniofacial asymmetry, craniosynostosis, bifid nasal tip, grooved nails, wiry hair, and abnormalities of the thoracic skeleton, whereas males typically show only hypertelorism (Twigg et al., 2004; Wieland et al., 2004).
The phenotypic spectrum of MED12-related disorders, which is still being defined, includes at a minimum the phenotypes of FG syndrome type 1 (FGS1), Lujan syndrome (LS), and X-linked Ohdo syndrome. FGS1 and LS share the clinical findings of cognitive impairment, hypotonia, and abnormalities of the corpus callosum. FGS1 is further characterized by absolute or relative macrocephaly, tall forehead, downslanted palpebral fissures, small and simple ears, constipation and/or anal anomalies, broad thumbs and halluces, and characteristic behavior. LS is further characterized by large head, tall thin body habitus, long thin face, prominent nasal bridge, high narrow palate, and short philtrum. Carrier females in families with FGS1 and LS are typically unaffected. X-linked Ohdo syndrome (referred to as XLOS in this GeneReview) is characterized by intellectual disability, blepharophimosis, and facial coarsening. A number of individuals with nonsyndromic intellectual disability – including some affected females – have been described.
A birth defect is a problem that happens while a baby is developing in the mother's body. Most birth defects happen during the first 3 months of pregnancy. One out of every 33 babies in the United States is born with a birth defect. A birth defect may affect how the body looks, works or both. Some birth defects like cleft lip or neural tube defects are structural problems that can be easy to see. To find others, like heart defects, doctors use special tests. Birth defects can range from mild to severe. Causes can include. -Genetics. -Exposures to medicines or chemicals. For example, alcohol abuse can cause fetal alcohol syndrome. -Infections during pregnancy. -Certain medicines. Before you get pregnant, talk to your health care provider about any medicines you take. -Not getting enough of certain nutrients. For example, not getting enough folic acid before and during pregnancy is a key factor in causing neural tube defects. For most birth defects, the cause is unknown. Health care providers can diagnose certain birth defects during pregnancy, with prenatal tests. That's why it important to get regular prenatal care. Other birth defects may not be found until after the baby is born. Sometimes the defect is obvious right away. Other times, the health care provider may not discover it until later in life. Babies with birth defects often need special care and treatments. The treatments may include surgery, medicines, assistive devices, and therapies. Centers for Disease Control and Prevention.
partially saturated derivative of pyridine; binds to and inhibits the voltage-gated calcium channel of skeletal muscle T junctional membranes, the principle molecular transducer of excitation-contraction coupling.
abnormal increase in the depth and rate of respiratory movements.
A feeling of faintness; a reeling sensation. Lightheadedness is medically distinct from dizziness, unsteadiness, and vertigo.
An aromatic fatty acid metabolite of phenylalanine with potential antineoplastic activity. Naturally occurring in mammals, phenylacetate induces differentiation, growth inhibition, and apoptosis in tumor cells. Implicated mechanisms of action include decreased protein prenylation, activation of the peroxisome proliferation-activated receptors, inhibition of DNA methylation, and depletion of glutamine. (NCI04)
Acid accumulation or depletion of base in the body due to buildup of metabolic acids.
Acidosis resulting from accumulation of ketone bodies.
Abnormally increased pH levels in the blood due to excessive loss of acid and/or accumulation of base.
An extremely rare autosomal recessive inherited disorder caused by mutations in the UMPS gene. It is characterized by deficiency of the activity of the pyrimidine pathway enzyme uridine 5'-monophosphate (UMP) synthase. Clinical manifestations include growth retardation, anemia, and increased excretion of orotic acid in the urine.
An increased concentration of xanthine in the urine.
Acquired partial lipodystrophy is characterized clinically by the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the 'cephalocaudal' sequence, sparing the lower extremities (summary by Misra et al., 2004). The disorder is not inherited in a classic mendelian pattern; it rather represents a phenotype with a complex etiology. Affected individuals may have genetic susceptibility factors that require the additional presence of environmental factors or acquired disorders to be expressed (summary by Hegele et al., 2006). Most cases are sporadic, family history is negative, and females are more often affected than males (ratio, 4:1). There is an association between APLD and autoimmune diseases (Misra and Garg, 2003; Misra et al., 2004), and a subset of patients have APLD associated with low serum complement component C3 and the autoantibody C3 nephritic factor, with or without membranoproliferative glomerulonephritis (APLDC3; 613913). Acquired partial lipodystrophy is distinct from inherited forms of partial lipodystrophy, which are metabolic disorders that show clear mendelian inheritance (see, e.g., FPLD1, 608600).
Rotor syndrome is characterized by mild conjugated and unconjugated hyperbilirubinemia which usually begins shortly after birth or in childhood. Jaundice may be intermittent. Conjunctival icterus may be the only clinical manifestation.
Histidinemia is a metabolic disorder characterized by increased levels of histidine in blood, urine, and cerebrospinal fluid, and decreased levels of the metabolite urocanic acid in blood, urine, and skin cells. Although histidinemia was originally associated with mental retardation and speech defects, it is generally considered to be a benign disorder (Levy et al., 2001). However, it is possible that histidinemia may be a risk factor for developmental disorders in certain individuals under specific circumstances, such as perinatal events (Ishikawa, 1987).
Cystathioninuria, an autosomal recessive phenotype with no striking pathologic features, is characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion. Because of the inconsistency and wide variety of disease associations, cystathioninuria is considered to be a benign biochemical anomaly (Mudd et al., 2001).
A laboratory test result demonstrating an increased concentration of ammonia in the blood.
A type of hypothyroidism that results from a defect in thyrotropin-releasing hormone activity.
A condition of abnormally elevated output of PARATHYROID HORMONE due to parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. It is characterized by the combination of HYPERCALCEMIA, phosphaturia, elevated renal 1,25-DIHYDROXYVITAMIN D3 synthesis, and increased BONE RESORPTION.
A complication of poorly controlled type 1 diabetes mellitus in children characterized by linear growth impairment, glycogenic hepatopathy, and Cushingoid features.
A rare disorder of unknown etiology. It may present as a cutaneous disorder with a benign clinical course or a systemic disorder with a grim prognosis. Both the cutaneous and systemic variants are characterized by the presence of papular skin lesions. The systemic variant, in addition to the skin papules, is characterized by gastrointestinal manifestations including abdominal pain and distention, nausea, vomiting, diarrhea, intestinal infarction, and intestinal perforation. The central and peripheral nervous systems may also be involved in the systemic variant.
Systemic mastocytosis is a blood disorder that can affect many different body systems. Individuals with the condition can develop signs and symptoms at any age, but it usually appears after adolescence.Signs and symptoms of systemic mastocytosis often include extreme tiredness (fatigue), skin redness and warmth (flushing), nausea, abdominal pain, bloating, diarrhea, the backflow of stomach acids into the esophagus (gastroesophageal reflux), nasal congestion, shortness of breath, low blood pressure (hypotension), lightheadedness, and headache. Some affected individuals have attention or memory problems, anxiety, or depression. Many individuals with systemic mastocytosis develop a skin condition called urticaria pigmentosa, which is characterized by raised patches of brownish skin that sting or itch with contact or changes in temperature. Nearly half of individuals with systemic mastocytosis will experience severe allergic reactions (anaphylaxis).There are five subtypes of systemic mastocytosis, which are differentiated by their severity and the signs and symptoms. The mildest forms of systemic mastocytosis are the indolent and smoldering types. Individuals with these types tend to have only the general signs and symptoms of systemic mastocytosis described above. Individuals with smoldering mastocytosis may have more organs affected and more severe features than those with indolent mastocytosis. The indolent type is the most common type of systemic mastocytosis.The severe types include aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. These types are associated with a reduced life span, which varies among the types and affected individuals. In addition to the general signs and symptoms of systemic mastocytosis, these types typically involve impaired function of an organ, such as the liver, spleen, or lymph nodes. The organ dysfunction can result in an abnormal buildup of fluid in the abdominal cavity (ascites). Aggressive systemic mastocytosis is associated with a loss of bone tissue (osteoporosis and osteopenia) and multiple bone fractures. Systemic mastocytosis with an associated hematologic neoplasm and mast cell leukemia both involve blood cell disorders or blood cell cancer (leukemia). Mast cell leukemia is the rarest and most severe type of systemic mastocytosis.Individuals with the milder forms of the condition generally have a normal or near normal life expectancy, while those with the more severe forms typically survive months or a few years after diagnosis.
Amyloidosis occurring secondary to another disease.
An inherited form of sideroblastic anemia.
A heterozygous state in which a person has a hemoglobin S allele along with a beta-thalassemia allele. The severity of the condition is determined to a large extent by the quantity of normal hemoglobin produced by the beta-thalassemia gene.
Acquired anemia due to destruction of red blood cells by physical trauma such as FIBRIN strands in the blood vessels, artificial heart valve, AORTIC COARCTATION. I can also be associated with hematologic diseases such as DISSEMINATED INTRAVASCULAR COAGULATION; HEMOLYTIC-UREMIC SYNDROME; and THROMBOTIC THROMBOCYTOPENIC PURPURA.
ELANE-related neutropenia includes congenital neutropenia and cyclic neutropenia, both of which are primary hematologic disorders characterized by recurrent fever, skin and oropharyngeal inflammation (i.e., mouth ulcers, gingivitis, sinusitis, and pharyngitis), and cervical adenopathy. Infectious complications are generally more severe in congenital neutropenia than in cyclic neutropenia. In congenital neutropenia, omphalitis immediately after birth may be the first sign; in untreated children diarrhea, pneumonia, and deep abscesses in the liver, lungs, and subcutaneous tissues are common in the first year of life. After 15 years with granulocyte colony-stimulating factor treatment, the risk of developing myelodysplasia (MDS) or acute myelogenous leukemia (AML) is approximately 15%-25%. Cyclic neutropenia is usually diagnosed within the first year of life based on approximately three-week intervals of fever and oral ulcerations and regular oscillations of blood cell counts. Cellulitis, especially perianal cellulitis, is common during neutropenic periods. Between neutropenic periods, affected individuals are generally healthy. Symptoms improve in adulthood. Cyclic neutropenia is not associated with risk of malignancy or conversion to leukemia.
A cavernous angiomatosis associated with the destruction of platelets, resulting in thrombocytopenia.
X-linked agammaglobulinemia (XLA) is characterized by recurrent bacterial infections in affected males in the first two years of life. Recurrent otitis is the most common infection prior to diagnosis. Conjunctivitis, sinopulmonary infections, diarrhea, and skin infections are also frequently seen. Approximately 60% of individuals with XLA are recognized as having immunodeficiency when they develop a severe, life-threatening infection such as pneumonia, empyema, meningitis, sepsis, cellulitis, or septic arthritis. S pneumoniae and H influenzae are the most common organisms found prior to diagnosis and may continue to cause sinusitis and otitis after diagnosis and the initiation of gammaglobulin substitution therapy. Severe, difficult-to-treat enteroviral infections (often manifest as dermatomyositis or chronic meningoencephalitis) can be prevented by this treatment. The prognosis for individuals with XLA has improved markedly in the last 25 years as a result of earlier diagnosis, the development of preparations of gammaglobulin that allow normal concentrations of serum IgG to be achieved, and more liberal use of antibiotics.
A condition characterized by a decrease in the number of platelets in the blood below established reference ranges in a newborn.
any syndrome associated with increased viscosity of the blood; in syndrome of serum hyperviscosity there is spontaneous bleeding and neurologic and ocular disorders; syndromes of polycythemic hyperviscosity is marked by retarded blood flow, organ congestion, reduced capillary perfusion, and increased cardiac effort; syndromes of sclerocythemic hyperviscosity comprise those in which the deformability of erythrocytes is impaired, as in sickle cell anemia.
Berardinelli-Seip congenital lipodystrophy (BSCL) is usually diagnosed at birth or soon thereafter. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality.
Triple X syndrome, also called trisomy X or 47,XXX, is characterized by the presence of an additional X chromosome in each of a female's cells. Although females with this condition may be taller than average, this chromosomal change typically causes no unusual physical features. Most females with triple X syndrome have normal sexual development and are able to conceive children.Triple X syndrome is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills (such as sitting and walking), weak muscle tone (hypotonia), and behavioral and emotional difficulties are also possible, but these characteristics vary widely among affected girls and women. Seizures or kidney abnormalities occur in about 10 percent of affected females.
An autosomal recessive genetic disorder caused by mutations in the SLC39A4 gene, encoding zinc transporter ZIP4. The condition is characterized by zinc deficiency, periorificial and acral dermatitis, and diarrhea.
A severe, often fatal encephalopathy which has been attributed to accumulation in the brain of aluminum from dialysate prepared with inadequately purified water.
Liddle syndrome is an autosomal dominant disorder characterized by early-onset salt-sensitive hypertension, hypokalemia, metabolic alkalosis, and suppression of plasma renin activity and aldosterone secretion (summary by Yang et al., 2014). Genetic Heterogeneity of Liddle Syndrome Liddle syndrome-2 (618114) is caused by mutation in the SCNN1G gene (600761), which encodes the ENaC gamma subunit. Liddle syndrome-3 (618126) is caused by mutation in the SCNN1A gene (600228), which encodes the ENaC alpha subunit. Hanukoglu and Hanukoglu (2016) provided a detailed review of the ENaC gene family, including structure, function, tissue distribution, and associated inherited diseases.
An exaggerated response to carotid sinus baroreceptor stimulation resulting in syncope from transient diminished cerebral perfusion.
Welander distal myopathy is an autosomal dominant disorder characterized by adult onset of distal muscle weakness predominantly affecting the distal long extensors of the hands, with slow progression to involve all small hand muscles and the lower legs. Skeletal muscle biopsy shows myopathic changes and prominent rimmed vacuoles. Rare homozygous patients showed earlier onset, faster progression, and proximal muscle involvement. This disorder is common in Sweden and Finland (summary by Hackman et al., 2013).
Paramyotonia congenita is a disorder that affects muscles used for movement (skeletal muscles). Beginning in infancy or early childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness that typically appears after exercise and can be induced by muscle cooling. This stiffness chiefly affects muscles in the face, neck, arms, and hands, although it can also affect muscles used for breathing and muscles in the lower body. Unlike many other forms of myotonia, the muscle stiffness associated with paramyotonia congenita tends to worsen with repeated movements.Most people—even those without muscle disease—feel that their muscles do not work as well when they are cold. This effect is dramatic in people with paramyotonia congenita. Exposure to cold initially causes muscle stiffness in these individuals, and prolonged cold exposure leads to temporary episodes of mild to severe muscle weakness that may last for several hours at a time. Some older people with paramyotonia congenita develop permanent muscle weakness that can be disabling.
Childhood-onset of recurrent headaches with an oculomotor cranial nerve palsy. Typically, ABDUCENS NERVE; OCULOMOTOR NERVE; and TROCHLEAR NERVE are involved with DIPLOPIA and BLEPHAROPTOSIS.
The most basic description of Moebius syndrome is a congenital facial palsy with impairment of ocular abduction. The facial nerve (cranial nerve VII) and abducens nerve (CN VI) are most frequently involved, but other cranial nerves may be involved as well. Other variable features include orofacial dysmorphism and limb malformations. Mental retardation has been reported in a subset of patients. Most cases of Moebius syndrome are sporadic, but familial occurrence has been reported (Verzijl et al., 2003). The definition of and diagnostic criteria for Moebius syndrome have been controversial and problematic. The syndrome has most frequently been confused with hereditary congenital facial paresis (see 601471), which is restricted to involvement of the facial nerve and no other abnormalities. Verzijl et al. (2003) and Verzijl et al. (2005) concluded that HCFP and Moebius syndrome are distinct disorders, and that Moebius syndrome is a complex developmental disorder of the brainstem. Moebius syndrome was defined at the Moebius Syndrome Foundation Research Conference in 2007 as congenital, nonprogressive facial weakness with limited abduction of one or both eyes. Additional features can include hearing loss and other cranial nerve dysfunction, as well as motor, orofacial, musculoskeletal, neurodevelopmental, and social problems (summary by Webb et al., 2012). Kumar (1990) provided a review of Moebius syndrome, which was critiqued by Lipson et al. (1990). Briegel (2006) provided a review of Moebius sequence with special emphasis on neuropsychiatric findings.
'Behr syndrome' is a clinical term that refers to the constellation of early-onset optic atrophy accompanied by neurologic features, including ataxia, pyramidal signs, spasticity, and mental retardation (Behr, 1909; Thomas et al., 1984). Patients with mutations in genes other than OPA1 can present with clinical features reminiscent of Behr syndrome. Mutations in one of these genes, OPA3 (606580), result in type III 3-methylglutaconic aciduria (MGCA3; 258501). Lerman-Sagie (1995) noted that the abnormal urinary pattern in MGCA3 may not be picked up by routine organic acid analysis, suggesting that early reports of Behr syndrome with normal metabolic features may actually have been 3-methylglutaconic aciduria type III.
A neuropathy due to VITAMIN B 12 DEFICIENCY or to excessive NITROUS OXIDE inhalation. It is associated with overproduction of the myelinolytic TUMOR NECROSIS FACTOR-ALPHA.
Ischemia or infarction of the spinal cord in the distribution of the anterior spinal artery, which supplies the ventral two-thirds of the spinal cord. This condition is usually associated with ATHEROSCLEROSIS of the aorta and may result from dissection of an AORTIC ANEURYSM or rarely dissection of the anterior spinal artery. Clinical features include weakness and loss of pain and temperature sensation below the level of injury, with relative sparing of position and vibratory sensation. (From Adams et al., Principles of Neurology, 6th ed, pp1249-50)
A type of clinical depression that occurs after childbirth.
An increase in the viscosity of blood resulting from an increase in the proportion of cellular elements of the blood, a change in the mechanical properties of the cellular elements of the blood, and/or an alteration in plasma viscosity.
Forceful expulsion of the contents of the stomach through the mouth.
Hypertension that presents intermittently.
Abnormally high systolic blood pressure.
An electrocardiographic finding of a supraventricular arrhythmia characterized by 3 or more distinct P wave morphologies with an isoelectric baseline, variable PR intervals and no predominant atrial rhythm. The ventricular rate is typically 100-150 beats per minute. (CDISC)
Motor skills deficits that significantly and persistently interfere with ACTIVITIES OF DAILY LIVING appropriate to chronological age. (from DSM-V)
Paralysis affecting corresponding parts on both sides of the body.
A slight paralysis or weakness of both legs.
Gout affecting the Metatarsophalangeal joint of big toe.
Hemiballismus is a rare movement disorder that is caused primarily by damage to various areas in the basal ganglia. Hemiballismus is usually characterized by involuntary flinging motions of the extremities. The movements are often violent and have wide amplitudes of motion. They are continuous and random and can involve proximal and/or distal muscles on one side of the body, while some cases even include the facial muscles. The more a patient is active, the more the movements increase. With relaxation comes a decrease in movements.
A condition in which muscles cannot be moved quickly without accompanying pain or spasm.
Ventral, lateral, or ventrolateral bowing of the shaft and glans penis of more than 30 degrees.
A localized pathological or traumatic structural change, damage, deformity, or discontinuity of tissue, organ, or body part.
An abnormality of the creases of the skin of palm of hand.
An outbreak of small, flat, red spots on the skin.
Dissolution of bone that particularly involves the removal or loss of calcium.
Urticaria may be caused by cold temperatures. [PMID:11702618]
A congenital abnormality characterized by the failure of the kidney to ascend to its normal position and it remains in the pelvis.
A congenital abnormality in which the intestine is abnormally rotated (twisted). It may result in intestinal obstruction.
A developmental defect of the aortic arch system in which the trachea and esophagus are completely encircled by connected segments of the aortic arch and its branches. This occurs if the normal process of regression and persistence of the bilateral embryonic aortic arches fails.
A ventricular septal defect that involves the inlet of the right ventricular septum immediately inferior to the AV valve apparatus.
A congenital, usually bilateral, thick web-like fold of skin that extends from the acromion to the mastoid process. This deformity is associated with Turner Syndrome and Noonan Syndrome.
Distended and engorged umbilical veins which are seen radiating from the umbilicus across the abdomen to join systemic veins.
A clogged cutaneous sebaceous follicle, which is a cutaneous gland that secretes sebum (usually into a hair follicle).
A smooth, slightly elevated area on the body surface, which is redder or paler than the surrounding skin. It is the typical lesion of urticaria, the dermal evidence of allergy, and in sensitive persons may be provoked by mechanical irritation of the skin.
A type of inflammation of the lips involving one or both of the corners of the mouth.
A focal inflammation of glomeruli secondary to mesangial cell proliferation and matrix deposition within the mesangium.
Inflammation of the glomeruli that is characterized by a rapid loss in renal function with glomerular crescent formation observed on biopsy; it is often seen in patients with concomitant autoimmune disease, like Goodpasture's syndrome or systemic lupus erythematosus.
Round areas of red-purple reaction in the skin that result after drug exposure; these recur in the same location when the medication is readministered.
Acral or periorificial lesions that evolve in recurrent crops, with an annular and migratory distribution.
Excessive shedding of dry scaly material from the scalp in humans.
A clearly-defined and roughly linear cleavage in the skin that usually extends to the dermis.
Eruptive xanthomas are yellow-orange-to-red-brown papules that are often surrounded by an erythematous halo. They appear in crops on the buttocks, extensor surfaces of the extremities, and flexural creases. Acutely, variable amounts of pruritus and pain occur.
The presence of xanthomas (intra-and extra-cellular accumulations of cholesterol) extensor tendons (typically over knuckles, Achilles tendon, knee, and elbows).
A disease of the eye in which the eyelashes abnormally turn inwards toward the eyeball producing constant irritation caused by motion of the lids.
Deformity or discoloration of a fingernail or toenail.
The natural longitudinal (posterodistal) convex arch is not present or is inverted.
Circumscribed depigmentation of the hair of the head or the eyelashes.
A light brown, sharply demarcated skin patch. It is a manifestation of neurofibromatosis type 1 and McCune-Albright syndrome.
A reduction from normal of the mean corpuscular volume, or mean cell volume (MCV) of red blood cells (usually defined as an MCV below 80 femtoliters).
A group of disorders having a benign course but exhibiting clinical and histological features suggestive of malignant lymphoma. Pseudolymphoma is characterized by a benign infiltration of lymphoid cells or histiocytes which microscopically resembles a malignant lymphoma. (From Dorland, 28th ed & Stedman, 26th ed)
Diffuse hypertrophy of the stratum spinosum layer of the epidermis.
A non-neoplastic hamartomatous polyp that arises from the stomach and intestinal tract. It is characterized by the presence of tortuous and cystically dilated glands, edematous changes, and inflammation.
A lymphocyte that may be irregular or not conforming to type.
Abnormally increased variability in the size of erythrocytes.
An increase in the number of abnormally shaped red blood cells.
Increased amount of stacking of erythrocytes into long chains. Rouleaux (singular: rouleau) is derived from a French word that can refer to a stack of coins put into a cylindircal paper roll. Rouleaux formation is observed with increased serum proteins, particularly fibrinogen and globulins, and represents the cause of increased erythrocte sedimentation rate because rouleaux sediment more readily than isolated red blood cells. [HPO:probinson, PMID:16739263]
A premalignant condition morphologically characterised by the presence of the characteristic Paget cells in the intraepithelial tissue of the penis. It presents as a smooth raised reddish area that may or may not be painful. -- 2003
A rare tumor containing unequivocal elements of both hepatocellular and cholangiocarcinoma that are intimately admixed. This tumor should be distinguished from separate hepatocellular carcinoma and cholangiocarcinoma arising in the same liver. The prognosis of this tumor is poor.
A benign neoplasm arising from the synovial membrane. Examples include the diffuse giant cell tumor of tendon sheath and localized giant cell tumor of tendon sheath.
An uncommon benign cartilaginous neoplasm arising from the bone. It is characterized by the presence of spindle-shaped or stellate chondrocytes, a lobulated growth pattern, myxoid stroma formation, and sometimes multinucleated giant cells. It has been associated with chromosomal rearrangement of 6q13 and 6q25 bands. The most common clinical symptom is mild, localized pain.
An abnormally low level of uric acid in the blood.
Persistent, symmetric, and painless blue discoloration of the extremities. It is the result of vasospasm in response to cold. The affected areas are cold and sweaty.
Yellow nail syndrome (YNS) is classically considered to comprise a clinical triad of yellow nails, lymphedema, and respiratory tract involvement. Two of these symptoms are required for the diagnosis, since the complete triad is only observed in about one-third of patients. Onset is usually after puberty (Hoque et al., 2007).
Webbing or fusion of the fingers, involving soft parts only or including bone structure. Bony fusions are referred to as ""bony"" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers in a proximo-distal axis are referred to as ""Symphalangism"".
A congenital abnormality in which the two kidneys fuse together during fetal development to create a horseshoe-shaped structure.
A skeletal deformity characterized by an unusually prominent forehead. Causes include acromegaly, Hurler syndrome, Silver-Russell syndrome, and thalassemia major.
Primary megalencephaly is defined as a head circumference about the 98th percentile that most likely is due to brain enlargement and is not secondary to disease (review by Petersson et al., 1999).
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Congenital anomaly of abnormally short fingers or toes.
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Congenital lack, i.e., aplasia of the diaphragm.
Visually assessable vertical indentation, cleft, or depression of the nasal bridge, ridge and tip.
A complete duplication of the ureter such that the duplicated ureters with separate insertions into the bladder.
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middel fingers as far as oligo- or monodactyl hands.
Fluid accumulation and dilatation of the fallopian tube due to tubal blockage.
Inflammation of the vagina due to thinning of the vaginal wall and decreased lubrication associated with reduced estrogen levels at MENOPAUSE.
A state of ill health, bodily malfunction, or discomfort.
Neurotic disorder developed as a consequence of occupational stress, inappropriate occupational choice, overwork, job dissatisfaction, or other job-related stress.
Personality marked by self-destructiveness or self-defeating behavior, a conscious or unconscious need to suffer, and seeking out opportunities for suffering or self-injury.
Social, psychological, or emotional difficulties in adapting to a new culture or similar difficulties in adapting to one's own culture as the result of rapid social or cultural changes.
Compromise in intracranial fluid dynamic mechanisms that normally compensate for increases in intracranial volumes, resulting in repeated disproportionate increases in intracranial pressure (ICP) in response to a variety of noxious and non-noxious stimuli.
A pattern of community activities for adaptation and problem-solving that is unsatisfactory for meeting the demands or needs of the community.
Disintegration of the physiological and neurobehavioral systems of functioning.
Irreversible, progressive, insidious, and long-term alteration of intellect, behavior and personality, manifested by impairment in cognitive functions (memory, speech, language, decision making, and executive function), and dependency in execution of daily activities
A lack of strength of the proximal muscles. [HPO:probinson]
Syndesmophytes: osseous excrescences or bony outgrowths from the spinal ligaments as they attach to adjacent vertebral bodies. In psoriasis and in Reiter's syndrome, they often are massive and bridge adjacent vertebrae asymmetrically. In these diseases they appear to arise from a broad zone on the vertebrae, and tend to spare the anterior surfaces of the vertebrae (non-marginal syndesmophytes). In ankylosing spondylitis, however, the syndesmophytes (marginal) tend to be thinner, more vertical, and symmetrical, involving anterior as well as the lateral vertebral body margins. The disc space is often narrowed, and vertebral bodies may show anterior end plate erosions and appear to lose the normal anterior concavity (squaring).
Blockage of a bronchus passage most often by bronchial secretions and exudates.
Painful sensation in the esophageal region.
Alpha-1 antitrypsin deficiency (AATD) is characterized by an increased risk for: chronic obstructive pulmonary disease (i.e., emphysema, persistent airflow obstruction, and/or chronic bronchitis) in adults; liver disease in children and adults; panniculitis; and c-ANCA positive vasculitis. Emphysema, sometimes with associated bronchiectasis, is the most common manifestation of AATD. Smoking is the major factor influencing the course of chronic obstructive pulmonary disease (COPD). The onset of respiratory disease in smokers with AATD is characteristically between ages 40 and 50 years; in non-smokers, the onset can be delayed to the sixth decade, and some non-smokers never develop COPD. Non-smokers may have a normal life span. Although reported, emphysema in children with AATD is extremely rare. AATD-associated liver disease, which is present in only a small portion of affected children, manifests as obstructive jaundice and increased serum aminotransferase levels in the early days and months of life. The incidence of liver disease increases with age. Liver disease in adults (manifesting as cirrhosis and fibrosis) may occur in the absence of a history of neonatal or childhood liver disease. The risk for hepatocellular carcinoma (HCC) is increased in individuals with AATD.
A syndrome associated with inflammation of the BRACHIAL PLEXUS. Clinical features include severe pain in the shoulder region which may be accompanied by MUSCLE WEAKNESS and loss of sensation in the upper extremity. This condition may be associated with VIRUS DISEASES; IMMUNIZATION; SURGERY; heroin use (see HEROIN DEPENDENCE); and other conditions. The term brachial neuralgia generally refers to pain associated with brachial plexus injury. (From Adams et al., Principles of Neurology, 6th ed, pp1355-6)
Recurrent infections of the urinary bladder.
A separation of the rectus abdominis muscle into right and left halves (which are normally joined at the midline at the linea alba).
Abnormally high level of amylase in the blood.
Painful sensation in the mouth, tongue, or lips.
Sporadic enlargement of the thyroid gland that is not associated with changes in thyroid function or malignancy.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the wrist.
Alkaloids found in OPIUM from PAPAVER and their derivatives that induce analgesic and narcotic effects by action upon OPIOID RECEPTORS.
A congenital anomaly of the spine, where an extra or supernumerary lumbar vertebra arises from below the 5th lumbar vertebra.
An elongated, tapering, generally thick-walled sclerenchyma cell of vascular plants; its walls may or may not be lignified.
A common gynecologic disorder characterized by an abnormal, nonbloody discharge from the genital tract.
Any physical or mental impairment that interferes with an individual's ability to perform desired activities.
A feeling of general discomfort or uneasiness, an out-of-sorts feeling.
Without clinical signs or indications that raise the possibility of a particular disorder or dysfunction.
An event in which the patient reports pain that is severe, uncontrolled, and causing distress for the patient, family members, or both.
Functions related to susceptibility to fatigue, at any level of exertion.
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Abnormally increased weight-to-height squared ratio, calculated by dividing the individual's weight in kilograms by the square of the individual's height in meters and used as an indicator of underweight compared to averages.
Abnormally decreased weight-to-height squared ratio, calculated by dividing the individual's weight in kilograms by the square of the individual's height in meters and used as an indicator of underweight compared to averages.
The inability to maintain a comfortably body temperature in warm or hot weather.
the condition of a patient in the period following a surgical operation.
A state of physiological or psychological stress that cannot be compensated for by normal adaptive measures.
A chronobiologic disorder resulting from rapid travel across a number of time zones, characterized by insomnia or hypersomnolence, fatigue, behavioral symptoms, headaches, and gastrointestinal disturbances. (From Cooper, Sleep, 1994, pp593-8)
Changes in the organism associated with senescence, occurring at an accelerated rate.
Intake of nutrients insufficient to meet metabolic needs.
Diminished ability to maintain the tissues of the oral cavity
Potential for the inability to maintain body temperature within normal range.
Change in or modification of excretion of the waste matter of the kidneys
Incapacity to carry out physiological or psychological daily activities
Periods of suspended motor and sensory activity and periods of inactivity, repose, or mental calm.
Demonstrates a pattern of uncertainty to select the most appropriate course of action that aligns with health-related goals and values.
Imbalance in the ability to distinguish between the self and the non-self
A pattern of behavior and self-expression that does not match the environmental context, norms, and expectations.
Break in the continuity of family functioning which fails to support the well-being of its members.
Susceptible to primary caregiver difficulty in creating, maintaining or regaining an environment that promotes the optimum growth and development of the child, which may compromise the well-being of the child.
Change in or modification of nurturing figures ability to promote growth and development of infant/child
Increased chance of harming self or others
A response indicating that an individual is not mobile.
A finding indicating that joints, muscles, and/or tendons can extend beyond their normal limit.
Flexion of a limb or part beyond its normal range.
Involuntary flexion or extension of the arms and legs.
A type of rigidity in which the arms are in flexion and adduction and the legs are extended. This signifies a lesion in the cerebral white matter, internal capsules, or thalamus.
The occurrence of a single contraction or a series of contractions of a muscle.
Fine, rapid twitching of individual muscle fibers with little or no movement of the muscle as a whole. If a motor neuron or its axon is destroyed, the muscle fibers it innervates undergo denervation atrophy. This leads to hypersensitivity of individual muscle fibers to acetyl choline so that they may contract spontaneously. Isolated activity of individual muscle fibers is generally so fine it cannot be seen through the intact skin, although it can be recorded as a short-duration spike in the EMG.
Joint crepitance on physical examination: Crepitation refers to repeated crackling sounds. Joint crepitation refers to the palpable or audible grating or crunch sensation that occurs with motion. Crepitus occurs when coarse or roughened cartilage surfaces are moved against each other.
Weakness of the inferior portion of the rectus abdominal muscle, which is ascertained clinically as follows. When a patient sits up or raises the head from a recumbent position, the umbilicus is displaced toward the head. This is the result of paralysis of the inferior portion of the rectus abdominal muscle, so that the upper fibres predominate pulling upwards the umbilicus.
A sudden pain, usually sharp, occurring during movement, or exacerbated by movement, and prompting cessation of movement
A condition in which the affected individual cannot extend the wrist, which hangs flaccidly.
Bending or curvature of a finger toward the ulnar side (i.e., away from the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly.
A response indicating that a person's walking is normal postoperatively, with no alteration to gait.
Spasticity is manifested by increased stretch reflex which is intensified with movement velocity. This results in excessive and inappropriate muscle activation which can contribute to muscle hypertonia. Spastic gait is characterized by manifestations such as muscle hypertonia, stiff knee, and circumduction of the leg.
A type of gait (walking) characterized by by dragging one's feet along or without lifting the feet fully from the ground.
A form of gait abnormality characterized by hypertonia and flexion in the legs, hips and pelvis accompanied by extreme adduction leading to the knees and thighs hitting, or sometimes even crossing, in a scissors-like movement. The opposing muscles (abductors) become comparatively weak from lack of use. [HPO:probinson]
Useful in assessing for developmental dysplasia of the hip, this test is performed when the thigh is pushed posteriorly and the hip is adducted. Should the hip become dislocated by this movement, the result is considered positive.
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the knee.
An abnormal retention of gas in the lungs during expiration, either as a result of complete or partial airway obstruction or as a result of abnormalities in pulmonary compliance.
Breathing movements in which the chest wall moves in on inspiration and out on expiration, in reverse of the normal movements. It may be seen in children with respiratory distress of any cause, which leads to indrawing of the intercostal spaces during inspiration. Patients with chronic airways obstruction also show indrawing of the lower ribs during inspiration, due to the distorted action of a depressed and flattened diaphragm. Crush injuries of the chest, with fractured ribs and sternum, can lead to a severe degree of paradoxical breathing.
An anomalous (adventitious) sound produced by the breathing process.
Vibration felt on the chest wall, either by examiner or subjective
The maximum volume of air that can be exhaled after slow maximum inhalation.
Extensive loss of blood due to internal or external hemorrhage.
A finding of decreased blood pressure; not necessarily hypotensive disorder
Weak or absent palpable pulse due to decreased arterial pulse pressure.
Pattern of blood flow in the heart that deviates from the normal circuit of the circulatory system.
An electrocardiographic finding of an atrial rhythm which originates from the sinoatrial node that is considered normal for the population. (CDISC)
An electrocardiographic finding of an atrial rhythm which originates from the sinoatrial node that is considered normal for the population. There are no extra beats or conduction abnormalities. (CDISC)
An electrocardiographic finding of a rhythm which originates in the AV junction and results in a normal heart rate. It is characterized by retrograde P waves which may be obscured by or may follow the QRS complexes. The QRS complexes may be narrow or may demonstrate aberration. (CDISC)
An electrocardiographic finding of a junctional rhythm that arises as a physiologic response to extreme slowing or arrest of sinus node activity. In this setting, a faster junctional rhythm may be a normal response to a very slow or absent sinus rate. (CDISC)
An electrocardiographic finding of a compensatory ventricular complex that occurs following a prolonged RR interval. (CDISC)
A ventircular escape rhythm occurs whenever higher-lever pacemakers in AV junction or sinus node fail to control ventricular activation. Escape rate is usually 20-40 bpm, often associated with broad QRS complexes are broad (at least 120 ms).
Lack of variation in the splitting between the two components of the second heart sound with respiration. Normally, the aortic valve closure (A2) is followed by the pulmonic valve closure (P2) but the A2-P2 interval increases with inspiration and decreases with expiration. []
Normally, the aortic valve closure (A2) is followed by the pulmonic valve closure (P2) but the A2-P2 interval increases with inspiration and decreases with expiration. With paradoxical splitting, there is a delay in the closure of the aortic valve, so that A2 can follow P2; the individual components can be appreciated at the end of expiration and the interval narrows with inspiration (which is the oposite of the normal pattern). []
The third heart sound (S3) is related to rapid filling in diastole. S3 can be a normal finding in children and adolescents but suggests heart failure in older patients. []
Any abnormality of the third heart sound
Any abnormality of the fourth heart sound
A heart murmur limited to systole, i.e., between the first and second heart sounds S1 and S2. []
A heart murmur that occurs during the entire systolic phase from S1 to S2. []
A systolic murmur that begins after S1 and ends before S2, typically with a crescendo-decrescendo pattern. []
A murmur that occurs in the latter phase of systole. []
A heart murmur that occurs during diastole, i.e., in the time between S2 and the subsequent S1. []
A murmur that occurs in the middle of the diastolic phase. []
A murmur that occurs in both systole and diastole. []
A sharp, high-pitched click heart sound that indicates heart valve disease
A galloping sound on cardiac auscultation because of an abnormally audible third heart sound.
Cardiac murmur with no significant crescendo or decrescendo
A question about whether an individual feels or has felt tightness in the chest.
An electrocardiographic finding suggesting underlying hypertrophy or dilatation of the right atrium. Electrocardiographic criteria used for the diagnosis of right atrial abnormality may include a peaked p wave greater than 2.5 millimeters in amplitude in the inferior leads.
A broad (120 ms or longer in duration) and bifid P-wave in EKG lead II. []
An electrocardiographic finding of a small hump following the T wave occurring during the final phase of Purkinje repolarization.
Markedly reduced or absent REPERFUSION in an infarct zone following the removal of an obstruction or constriction of an artery.
Change in or modification of the stomach or intestines
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Excessively active peristalsis (wave of contraction of the tubular organs of the gastrointestinal tract) marked by excessive rapidity of the passage of food through the stomach and intestine.
Reduced or inadequate peristalsis, with resultant slow passage of contents through the digestive tract. [HPO:probinson]
An abnormal backward flow of a body fluid.
A clinical syndrome with intermittent abdominal pain characterized by sudden onset and cessation that is commonly seen in infants. It is usually associated with obstruction of the INTESTINES; of the CYSTIC DUCT; or of the URINARY TRACT.
Pain that is localized to the region of the upper abdomen immediately below the ribs.
A sensation of discomfort emanating from the inferior quadrants of the abdomen, which may be peritoneal or visceral in origin, or referred from an extra-abdominal location.
Premature loss of teeth not related to trauma or neglect.
Involuntary spasms of the stomach and esophagus resulting in vomiting or dry heaving.
A repeated, painful urge to defecate without excreting stool.
Reduced ability of the liver to perform its functions. [HPO:probinson]
A clinical sign indicating a lapse of posture and is usually manifest by a bilateral flapping tremor at the wrist, metacarpophalangeal, and hip joints.
An abnormally low urinary specific gravity, i.e., reduced concentration of solutes in the urine.
Painful sensation in the bladder region.
The formation of CONGENITAL ABNORMALITIES.
The absence of a menstrual period based on the expected start date of the menstrual cycle.
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
The cessation of menstruation for six months or more in a female that is not pregnant, breastfeeding or menopausal.
Prolonged/excessive menses and bleeding at irregular intervals.
Having to do with the time after menopause. Menopause (""change of life"") is the time in a woman's life when menstrual periods stop permanently.
Observed to be negative for a pregnancy test or not pregnant.
Azoospermia, a condition in which there are no sperm present in the ejaculate, has historically been divided into 2 broad categories, obstructive (e.g., 277180) and nonobstructive. Among the genetically based, inherited nonobstructive causes are defects of spermatogenesis, which may interrupt the development of the sperm at various stages, either before (e.g., 415000) or during meiosis. SPGF4 is a form of azoospermia due to perturbations of meiosis. For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). Recurrent Pregnancy Loss Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks' gestation. Recurrent miscarriage, defined as 3 or more consecutive pregnancy losses, affects about 1% of couples; when defined as 2 or more losses, the scale of the problem increases to 5% of all couples trying to conceive (summary by Rai and Regan, 2006). Pregnancy losses have traditionally been designated 'spontaneous abortions' if they occur before 20 weeks' gestation and 'stillbirths' if they occur after 20 weeks. Subtypes of spontaneous abortions can be further distinguished on the basis of embryonic development and include anembryonic loss in the first 5 weeks after conception (so-called 'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal loss from 10 weeks' gestation through the remainder of the pregnancy. These distinctions are important because the causes of pregnancy loss vary over gestational ages, with anembryonic losses being more likely to be associated with chromosomal abnormalities, for example. Possible etiologies for recurrent pregnancy loss include uterine anatomic abnormalities, cytogenetic abnormalities in the parents or fetus, single gene disorders, thrombophilic conditions, and immunologic or endocrine factors as well as environmental or infectious agents (summary by Warren and Silver, 2008). For a discussion of genetic heterogeneity of recurrent pregnancy loss, see RPRGL1 (614389).
An endocrine state in men, characterized by a significant decline in the production of TESTOSTERONE; DEHYDROEPIANDROSTERONE; and other hormones such as HUMAN GROWTH HORMONE. Andropause symptoms are related to the lack of androgens including DEPRESSION, sexual dysfunction, and OSTEOPOROSIS. Andropause may also result from hormonal ablation therapy for malignant diseases.
A pregnancy that is normal for both the mother and the fetus.
Expulsion of all the products of conception following spontaneous, medical or operative pregnancy termination.
The number of uterine contractions recorded over a period of time, usually in minutes; measured from the start of one contraction to the start of the next.
Irregular infrequent uterine contractions typically characteristic of the third trimester of pregnancy that do not result in cervical change or labor.
A soft murmur heard in auscultating a pregnant uterus. It is caused by the increased vascularity of pregnancy.
The characteristic sign of impending birth during the second stage of labor. The presenting part of the head of fetus is visible and firmly rimmed by the maternal vaginal wall.
In a woman with a normal weight pre-pregnancy body mass index (BMI), i.e. 18.5-24.9, the weight gained during pregnancy does not exceed a total weight gain of 25 lbs. In a woman with an underweight pre-pregnancy body mass index (BMI), i.e. less than 18.5, the weight gained during pregnancy does not exceed a total weight gain of 28 lbs. In a woman with an overweight pre-pregnancy body mass index (BMI), i.e. 25.0-29.9, the weight gained during pregnancy does not exceed a total weight gain of 15 lbs. In a woman with an obese pre-pregnancy body mass index (BMI), i.e. greater than 30, the weight gained during pregnancy does not exceed a total weight gain of 11 lbs. These standards are supported for the whole population irrespective of height, race or ethnicity.
The movement of the fetus led by the presenting part into the maternal pelvic cavity during active labor.
A position assumed by fetal body parts to one another (head, chest, arms and legs) in relation to the chest.
A change in the position of the head of the fetus as it descends through the maternal pelvic cavity during labor and delivery.
A finding during labor, in which the occiput rotates anteriorly and the head of the fetus assumes an oblique orientation while the fetus descends through the maternal pelvis.
The repositioning of the fetal head attitude immediately after delivery, returning to a normal position in alignment with the rest of its body.
Any presentation other than a vertex presentation. (reVITALize)
A type of fetal presentation where the fetal spine is aligned along the longitudinal axis of the uterus and descends into the birth canal during delivery.
A fetal presentation where the head is presenting first in the pelvic inlet. Does not apply if compound or breech presentation or if brow, face, hand, shoulder, etc. present first in the pelvic inlet. (reVITALize)
A fetal presentation during delivery in which the face of the fetus is first to descend into the birth canal.
A fetal presentation during delivery in which the brow of the fetus is first to descend into the birth canal.
A kind of breech presentation in which the hips are flexed and the knees are flexed.
A kind of breech presentation in which the hips are flexed and the knees are extended.
The positioning of the umbilical cord before the main presenting part of the fetus.
A rupture of the fetal membranes that is not concurrent with or immediately following a digital exam or other transvaginal intervention involving the amniotic membrane.
The birth of a baby of less than 37 weeks of gestational age.
Impaired awareness of place, often characteristic of organic mental disorders.
Lack of emotional reactivity and empathy for situations or persons, sometime also for family members.
The absence of emotional expressiveness.
Mental distress resulting from concern for something impending or anticipated.
A feeling of mental or emotional strain or suspense.
An abnormality of mental functioning including various affective, behavioural, cognitive and perceptual abnormalities.
A deliberate pattern of behavior that demonstrates both willful aggression toward other people and an intentional disregard for the common, current norms of social conduct.
Struggle or disagreement between parents, parent and child or other members of a family.
Bradykinesia literally means slow movement, and is used clinically to denote a slowness in the execution of movement (in contrast to hypokinesia, which is used to refer to slowness in the initiation of movement).
Repetitive pressing, poking, and/or rubbing in the eyes.
Disturbances of thinking that affect thought content, language, and/or communication marked by delusions, incoherence, and profound loosening of associations.
Belief that one's utterances, thoughts, or behavior can have a controlling influence on specific events or prevent their occurrence by means that operate beyond the normal laws of cause and effect.
Unintelligible speech occurring in hypnotic or mediumistic trances, religious experiences, or some mental disorders.
Perseveration can be defined as the contextually inappropriate and unintentional repetition of a response or behavioral unit. In other words, the observed repetitiveness does not meet the demands of the situation, is not the product of deliberation, and may even unfold despite counterintention. Perseveration can therefore be differentiated from goal-directed and intentional forms of repetition, such as linguistic redundancies designed to enhance communicative or poetic impact.
Rapid succession of thoughts pertaining to different subjects that are still connected.
Difficulty in recollection, or interruption of a train of thought or speech, due to emotional factors.
Intense or irrational dislike or fear of anything that is strange or foreign, particularly of people who are strangers or foreigners. It is an attitudinal orientation of hostility against non-natives in a given population that includes attitudes, prejudices and behavior that reject, exclude or vilify persons, based on the perception that they are outsiders or foreigners to the community, society or national identity.
An overwhelming, irrational, and persistent fear of being diagnosed with cancer.
An overwhelming, irrational, and persistent fear of animals.
Abnormal increased rate and amount of speech, delivered with urgency.
Involuntary and repetitive utterances of obscene or socially inappropriate words or statements.
Physical characteristics of speech that indicate linguistic features such as stress, intonation, intensity, and duration of speech sounds.
A feeling of altered reality characterized by a feeling of unreality, or being unreal.
Perception of sound in the absence of a corresponding stimulus.
Optical perception of an object, person or event in the absence of a corresponding stimulus.
Perception of a smell in the absence of a corresponding stimulus.
Auras with taste sensations including acidic, bitter, salty , sweet or metallic tastes.
Perception of pressure or touch in the absence of a corresponding stimulus.
An alteration in visual perception that causes objects to appear smaller than their actual size.
An alteration in visual perception that causes objects to appear larger than their actual size.
False sensory perceptions without actual appropriate stimuli, occurring while falling asleep.
Mental disorder characterized by hallucinations occurring in a normal state of consciousness and attributable to specific organic factors.
Synesthesia is broadly defined as the experience of involuntary sensory crossactivation in which the presentation of a particular stimulus elicits a secondary sensory-perceptual experience (Barnett et al., 2008). Although this phenomenon can be acquired or transient due to trauma or drugs, there is a congenital or developmental form that shows familial patterns. Synesthesia can occur between any 2 sensory modalities, but the most common and best-studied forms of synesthesia involve the association of color with linguistic stimuli such as letters, numbers, or words, or with music ('colored hearing,' 'colored music'; Baron-Cohen et al., 1996). Other less common forms include the induction of tastes by words, the induction of touch by vision, the induction of shapes by tastes, and the personification of numbers (Barnett et al., 2008).
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
Loss of the ability to form new memories beyond a certain point in time. This condition may be organic or psychogenic in origin. Organically induced anterograde amnesia may follow CRANIOCEREBRAL TRAUMA; SEIZURES; ANOXIA; and other conditions which adversely affect neural structures associated with memory formation (e.g., the HIPPOCAMPUS; FORNIX (BRAIN); MAMMILLARY BODIES; and ANTERIOR THALAMIC NUCLEI). (From Memory 1997 Jan-Mar;5(1-2):49-71)
Giving untruthful answers to questions about situations or events that are not recalled due to loss of memory. Confabulation is not a conscious attempt to deceive.
A subjective feeling that an experience which has occurred before is being experienced for the first time.
Maladaptive judgment resulting from wish-fulfilling, impulsive decisions based on need for immediate infantile gratification.
Reduced ability to plan, poor decision making.
Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.
The characteristics in behavior that a certain person has.
An involuntary ejaculation of semen accompanying an erotic dream.
Difficulty of a male in achieving orgasm.
Functional neurological abnormalities related to dysfunction of the pyramidal tract.
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
A writing disability in the absence of motor or sensory deficits of the upper extremities, resulting in an impairment in the ability to write regardless of the ability to read and not due to intellectual impairment.
A finding indicating the complete absence of neurological reflexes.
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Hereditary hyperekplexia (HPX) is characterized by generalized stiffness immediately after birth that normalizes during the first years of life; excessive startle reflex (eye blinking and a flexor spasm of the trunk) to unexpected (particularly auditory) stimuli; and a short period of generalized stiffness following the startle response during which voluntary movements are impossible. Exaggerated head-retraction reflex (HRR) consisting of extension of the head followed by violent flexor spasms of limbs and neck muscles elicited by tapping the tip of the nose is observed in most children. Other findings include periodic limb movements in sleep (PLMS) and hypnagogic (occurring when falling asleep) myoclonus. Sudden infant death (SIDS) has been reported. Intellect is usually normal; mild intellectual disability may occur.
Involuntary lifting of the legs upon lifting a patient's head.
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs. [HPO:probinson]
A type of paresthesia (tingling, pins-and-needles, burning or numbness or stiffness) that occurs in the hands and feet and particularly in the fingers and toes.
A sensation of intensley hot or searing discomfort.
A dull persistent (usually moderately intense) pain.
Pain originating from internal organs (VISCERA) associated with autonomic phenomena (PALLOR; SWEATING; NAUSEA; and VOMITING). It often becomes a REFERRED PAIN.
A type of pain that is perceived in an area away from the site where the pain arises, such as facial pain caused by lesion of the VAGUS NERVE, or throat problem generating referred pain in the ear.
A sensation of discomfort or distress that spreads from one anatomic location to another.
A type of dyssynergy characterized by the lack of the ability to smoothly perform the elements of a voluntary movement in the appropriate order and speed.
An involuntary movement accompanying a volitional movement. It often refers to facial movements that accompany FACIAL PARALYSIS.
A tremor present when the limbs are active, either when outstretched in a certain position or throughout a voluntary movement. [HPO:curators]
A type of tremors that is triggered by holding a limb in a fixed position.
A resting tremor occurs when muscles are at rest and becomes less noticeable or disappears when the affected muscles are moved. Resting tremors are often slow and coarse.
A vision disorder that results from damage of the part of the cerebral cortex that is involved in the processing of visual information.
A state of depressed CENTRAL NERVOUS SYSTEM marked by stupor or insensibility.
A type of fluent aphasia characterized by an impaired ability to repeat one and two word phrases, despite retained comprehension. This condition is associated with dominant hemisphere lesions involving the arcuate fasciculus (a white matter projection between Broca's and Wernicke's areas) and adjacent structures. Like patients with Wernicke aphasia (APHASIA, WERNICKE), patients with conduction aphasia are fluent but commit paraphasic errors during attempts at written and oral forms of communication. (From Adams et al., Principles of Neurology, 6th ed, p482; Brain & Bannister, Clinical Neurology, 7th ed, p142; Kandel et al., Principles of Neural Science, 3d ed, p848)
An inability to recognize or interpret objects by sight.
Inability to recognize the form of objects by touch without visual input. That is, an impairment in the recognition of objects based only on based on the texture, size, weight and three-dimensional form of the object in the absence of any major somatosensory deficit. [HPO:probinson]
A condition in which a person who suffers illness or disability seems unaware of or denies the existence of the illness or disability.
An inability or difficulty differentiating among the fingers of either hand as well as the hands of others.
Impaired ability to recognize other human faces in the absence of a vision disorder. It may be a congenital disorder or the result of brain injury.
A defect in the motor ability that enables speech.
Abnormal coordination of muscles involved in speech.
A form of apraxia characterized by an acquired inability to carry out a complex motor activity despite the ability to mentally formulate the action. This condition has been attributed to a disruption of connections between the dominant parietal cortex and supplementary and premotor cortical regions in both hemispheres. (From Adams et al., Principles of Neurology, 6th ed, p57)
Seizures of with initial involvement of both cerebral hemispheres.
A convulsion marked by alternating contracting and relaxing of the muscles.
The condition of where images are correctly brought to a focus on the retina.
An anomaly in the ability to discriminate between or recognize colors. [HPO:probinson]
Delayed descent of the upper eyelid on downgaze. Also described by some authors as von Graefe sign. [ORCID:0000-0003-0986-4123]
With the eyes in primary position, the sclera is visible above the superior corneal limbus. [https://www.aao.org/bcscsnippetdetail.aspx?id=03ad3eb3-3445-4be2-9470-2c4845169b75, PMID:8719687]
An increase in the intraocular pressure which is determined by the balance of aqueous humour inflow and outflow, and that is 2 standard deviations above the population mean.
The presence of a characteristic high-pitched cry that sounds similar to the meowing of a kitten.
Cutaneous eruptions resembling acne, characterized by the presence of papulonodules, pustules, comedones, or cysts in the face, trunk, and extremities. Causes include infections and the use of certain medications (e.g., antibiotics and steroids).
Alteration of the normal characteristics of the fingernails or toenails. Examples include thickening, thinning, deformity, and separation from the nail bed.
An exanthema consisting of widespread pink-to-red macules (flat spots of 2-10 mm in diameter) or papules (red bumps) that blanch with pressure. The macules and papules may cluster and merge to form sheets over several days.
The pores of the skin are generally large and visible with a coarse or thick texture. The skin has a tendency to look dull and greasy and feels oily to the touch.
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
A postural abnormality characterized by the inability to stand without external support despite having sufficient muscle strength. [HPO:mtaboada, PMID:27821973]
A partial seizure in which consciousness is maintained.
A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as rhythmically tapping the fingers on the knee.
Loss of previously present mental abilities, generally in adults.
Condition of elevated sensory sensitivity, perception of risk of threats, and low threshhold for stimuli.
Membranous areas between cranial bones in a newborn that appear elevated or full.
Inflammation or degeneration of the peripheral motor nerves.
A term that refers to the clinical manifestations resulting from pathologic processes that affect the central and peripheral nervous system.
A decrease in ventilation secondary to impaired signals from the central nervous system.
A scintillating scotoma is a common visual aura that can preced a migraine, whereby a spot of flickering light near the center of the visual fields occurs. The spot prevents vision, and is thus termed scotoma. The scotoma can extend into one or more shimmering arcs of white or colored flashing lights.
An electrocardiographic recording with intermittent mid to high frequency artifact in one or more leads due to muscular tremor or movement rather than cardiac activity. (CDISC)
An absolute or relative decrease in retinal sensitivity extending from edge (periphery) of the visual field in a concentric pattern. The visual field is the area that is perceived simultaneously by a fixating eye.
A state of decreased activity in animals characterized by depressed metabolism, reduced body temperature, and low sensitivity to external stimuli.
A state of a lowered level of consciousness.
Deterioration in the ability to concentrate.
Hypertension characterized diastolic blood pressure greater than 90 mmHg on two occasions.
A cataract that affects the region of the lens directly beneath the capsule of the lens.
A reddish appearance over the white part (sclera) of the eye ranging from a a few enlarged blood vessels appearing as wiggly lines over the sclera to a bright red color completely covering to sclera.
Injury to the retina due to advanced age, toxicity, exposure to bright lights, or trauma.
Blockage of the normal flow of the intestinal contents in the colon.
Blockage of the normal flow of the small intestinal contents.
Hepatitis that is characterized by the presence of granulomas.
An increase in the level of ketone bodies in the blood. []
Excessive secretion of androgens from the adrenal glands or gonads. Clinical manifestations may include virilization.
Increased time for the complex comprised of the Q wave, R wave, and S wave as measured by the electrocardiogram (EKG).. In adults, normal values are 0.06 - 0.10 sec.
A disorder characterized by an electrocardiographic finding of episodic atrial fibrillation with abrupt onset and termination.
Deficient blood distribution to the limbs caused by narrowing or obstruction of the lumen of the peripheral arteries.
Reduced ability of the right ventricle to perform its function (to receive blood from the right atrium and to eject blood into the pulmonary artery), often leading top pitting peripheral edema, ascites, and hepatomegaly.
Finding characterized by slowing of blood flow to a peripheral body region in association with an increase in oxygen extraction from normally saturated arterial blood
Hypopnea is referring to breathing that is abnormally shallower and/or slow.
A granuloma that is located in lung tissue.
Bleeding originating from any part of the respiratory tract.
Inflammation of the submandibular lymph nodes.
A constellation of renal disorders characterized by an increase number of cells in the glomerulus; these disorders generally present with nephrotic syndrome, and generally progress to end stage renal failure over a matter of weeks to years, depending on the etiology. Examples include IgA nephropathy, membranoproliferative glomerulonephritis, and rapidly progressive glomerulonephritis.
Bleeding originating from any part of the urinary system.
An abnormal reduction in quantity or strength of fetal movements.
Spontaneous flow of milk from the breast, unassociated with childbirth or nursing.
Unanticipated desirable and beneficial effects resulting from a medical treatment.
An involuntary or voluntary pause in breathing, sometimes accompanied by loss of consciousness.
A congenital vascular malformation consisting of superficial and deep dilated capillaries in the skin which produce a reddish to purplish discolouration of the skin.
A rare benign condition, characterized by a papillary growth in the urinary tract with a central fibrovascular core. The latter is lined by normal urothelium.
An opening or hole in the NASAL SEPTUM that is caused by TRAUMA, injury, drug use, or pathological process.
A cystic cancerous tumor arising from the ovary.
A malignant tumor arising from the epithelium of the gallbladder. It is usually associated with the presence of gallstones. Clinical symptoms are not specific and usually present late in the course. Morphologically, most gallbladder carcinomas are adenocarcinomas; squamous cell carcinomas, adenosquamous carcinomas, signet ring carcinomas, and undifferentiated carcinomas can also occur.
Inflammation of the vitreous body, characterized by the presence of inflammatory cells and protein exudate in the vitreous cavity.
Leukemia that occurs during the neonatal period.
A condition causing exacerbation of the clinical features of neurofibromatosis.
Abnormal functioning of the central nervous system in the newborn period that may be due to a variety of etiologies including hypoxia/ischemia, metabolic disturbance, or infection.
An increase in the desirable and beneficial effects resulting from a medical treatment.
A reduction in the desirable and beneficial effects resulting from a medical treatment.
The lack of expected or desired effect related to a therapy.
A finding of congenital malformations in the kidney characterized by the presence of cysts of various sizes, primitive ducts, islands of metaplastic cartilage and undifferentiated mesenchyme, and the absence of cortico-medullary demarcation.
Diaphragmatic hernia that is present at birth.
Acute inflammation characterized by neutrophilic infiltration of the decidua.
Abnormally decreased lacrimation, that is, reduced ability to produce tears.
Congenital hypertrichosis lanuginosa is a rare disorder characterized by excessive lanugo hair present at birth covering the entire body surface except the mucosae, palms, and soles (summary by De Raeve and Keymolen, 2011).
A rupture in the gastric wall caused by traumatic or pathologic processes.
An abnormal accumulation of fluid beneath the skin of the legs. [HPO:probinson]
A rare peritoneal cavity disorder that is characterized by the development of dense fibrous tissue in the peritoneum and the creation of severe adhesions in the abdomen that result in partial or complete small bowel obstruction. It may be idiopathic or develop in patients who receive peritoneal dialysis treatment. Patients present with abdominal distention and pain.
A finding indicating the presence of an inflammatory or neoplastic cellular infiltrate in the lung parenchyma.
A laboratory test result indicating an increased concentration of calcitonin in the blood serum.
A non-metastasizing neoplasm that arises from the breast parenchyma in females.
Vestibular areflexia can be measured as the absence of the caloric nystagmus response in electronystagmography.
Any anomaly of the vocalizing of an infant's crying, i.e.,the typically loud voice production that is accompanied by tears and agitation.
An abnormality of the skull, the bony framework of the head which is comprised of eight cranial and fourteen facial bones.
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. [HPO:sdoelken]
A genetic or acquired metabolic disorder that is associated with zinc deficiency in the tissues.
A disorder referring to problems related to ejaculation. This category includes premature, delayed, retrograde, and painful ejaculation.
A finding indicating elevated concentrations of alpha-fetoprotein in the blood.
Pancreatic cancer shows among the highest mortality rates of any cancer, with a 5-year relative survival rate of less than 5%. By the time of initial diagnosis, metastatic disease is commonly present. Established risk factors include a family history of pancreatic cancer, a medical history of diabetes type 2, and cigarette smoking (summary by Amundadottir et al., 2009). Genetic Heterogeneity of Pancreatic Cancer Somatic mutations in pancreatic cancer occur in the KRAS (190070), CDKN2A (600160), MADH4 (600993), TP53 (191170), ARMET (601916), STK11 (602216), ACVR1B (601300), and RBBP8 (604124) genes. Susceptibility loci for pancreatic cancer include PNCA1 (606856), related to mutation in the PALLD gene on chromosome 4q32 (608092); PNCA2 (613347), related to mutation in the BRCA2 gene on chromosome 13q12 (600185); PNCA3 (613348), related to mutation in the PALB2 gene on chromosome 16p12 (610355); and PNCA4 (614320), related to mutation in the BRCA1 gene on chromosome 17q21 (113705). Occurrence of Pancreatic Cancer in Other Disorders Several familial cancer syndromes increase the risk of pancreatic cancer. The best characterized include hereditary nonpolyposis colon cancer syndrome (HNPCC; see 120435); hereditary breast-ovarian cancer syndrome due to mutations in BRCA2; Peutz-Jeghers syndrome (175200); the melanoma-pancreatic cancer syndrome (606719), caused by mutations in CDKN2A (600160); von Hippel-Lindau syndrome (193300), ataxia-telangiectasia (208900) (Swift et al., 1976), and juvenile polyposis syndrome (174900). Patients with hereditary pancreatitis (167800) resulting from gain-of-function mutations in the protease serine-1 gene (PRSS1; 276000) have a lifetime pancreatic cancer risk ratio of 57 and a cumulative incidence, to age 70 years, of 40% (Lowenfels et al., 1997).
Acromegaly is a condition resulting from overproduction of growth hormone by the pituitary gland in persons with closed epiphyses, and consists chiefly in the enlargement of the distal parts of the body. The circumference of the skull increases, the nose becomes broad, the tongue becomes enlarged, the facial features become coarsened, the mandible grows excessively, and the teeth become separated. The fingers and toes grow chiefly in thickness. [DDD:spark, HPO:probinson]
Inappropriate secondary sex characteristics in the neonate usually due to in utero androgen exposure.
A newborn infant who has weight and/or length at birth more than two standard deviations below the mean for the reference population of the same sex and gestational age.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the jaw. [HPO:probinson]
Subjective ictal phenomena that, in a given patient, may precede observable seizures; if alone, constitute a if alone, constitute a simple partial seizure.
A malignant neoplasm that shows clinical and/or pathologic progression.
Abnormal accumulation of fluid leading to swelling of the pharynx.
A teratogenic disorder observed in a newborn or child of a mother who was exposed to valproic acid during pregnancy. Manifestations include musculoskeletal abnormalities, intellectual disability, spina bifida, and distinctive facial features.
Nonsyndromic hearing loss is a partial or total loss of hearing that is not associated with other signs and symptoms. In contrast, syndromic hearing loss occurs with signs and symptoms affecting other parts of the body.Nonsyndromic hearing loss can be classified in several different ways. One common way is by the condition's pattern of inheritance: autosomal dominant (DFNA), autosomal recessive (DFNB), X-linked (DFNX), or mitochondrial (which does not have a special designation). Each of these types of hearing loss includes multiple subtypes. DFNA, DFNB, and DFNX subtypes are numbered in the order in which they were first described. For example, DFNA1 was the first type of autosomal dominant nonsyndromic hearing loss to be identified.The characteristics of nonsyndromic hearing loss vary among the different types. Hearing loss can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The term ""deafness"" is often used to describe severe-to-profound hearing loss. Hearing loss can be stable, or it may be progressive, becoming more severe as a person gets older. Particular types of nonsyndromic hearing loss show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones.Most forms of nonsyndromic hearing loss are described as sensorineural, which means they are associated with a permanent loss of hearing caused by damage to structures in the inner ear. The inner ear processes sound and sends the information to the brain in the form of electrical nerve impulses. Less commonly, nonsyndromic hearing loss is described as conductive, meaning it results from changes in the middle ear. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic hearing loss, particularly a type called DFNX2, involve changes in both the inner ear and the middle ear. This combination is called mixed hearing loss.Depending on the type, nonsyndromic hearing loss can become apparent at any time from infancy to old age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual.
A polyp that arises from the stomach. This category includes neoplastic polyps (intestinal-type adenomatous polyps, gastric-type adenomas, and fundic gland polyps), and non-neoplastic polyps (hyperplastic polyps and hamartomatous polyps).
A circumscribed loss of integrity of the mucous membrane.
A laboratory test result which indicates decreased levels of haptoglobin in a biological specimen.
Any of the mental or physical manifestations that accompany perimenopause and menopause.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the scrotum.
A non-neoplastic or neoplastic disorder that affects the male genital system. Representative examples of non-neoplastic disorders include infection, testicular torsion, and undescended testis. Representative examples of neoplastic disorders include germ cell tumors, carcinoma, lymphoma, and sarcoma.
A non-neoplastic or neoplastic disorder that affects the female genital system. Representative examples of non-neoplastic disorders include infection, endometriosis, and adenomyosis. Representative examples of neoplastic disorders include germ cell tumors, carcinoma, lymphoma, and sarcoma.
An abnormally increased level of immunoglobulin E in blood.
Pick disease refers to the neuropathologic finding of 'Pick bodies,' which are argyrophilic, intraneuronal inclusions, and 'Pick cells,' which are enlarged neurons. The clinical correlates of Pick disease of brain include those of frontotemporal dementia, which encompass the behavioral variant of FTD, semantic dementia, and progressive nonfluent aphasia (summary by Piguet et al., 2011). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), progressive supranuclear palsy (601104), and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease,' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies.
Processes and symptomatic effects resulting from abstinence from alcohol. Used for both human and animal populations.
Disorders related to or resulting from abuse or mis-use of alcohol.
Disorders related or resulting from use of amphetamines.
Disorders related or resulting from use of cocaine.
An anxiety disorder in which the symptoms of anxiety have been determined to be the direct physiological consequence of a general medical condition.
A pediatric disorder characterized by normal development for at least the first two years of life followed by a severe regression in language, social interaction, bowel or bladder control, and/or motor skills. The affected individual may also exhibit repetitive and stereotyped patterns of behavior similar to autism.
A disorder beginning in childhood whose essential features are persistent impairment in reciprocal social communication and social interaction, and restricted, repetitive patterns of behavior, interests, or activities. These symptoms may limit or impair everyday functioning. (From DSM-5)
A disorder in which an individual experiences recurrent, unexpected panic attacks and persistent concern about having additional panic attacks. Agoraphobia is not a component of this disorder.
A disorder characterized by a retrospective gap in memory of important personal information, usually of a traumatic or stressful nature; the memory loss far exceeds ordinary forgetfulness and is not the result of substance use or the consequence of a medical condition.
A disorder in which an individual experiences recurrent, unexpected panic attacks and persistent concern about having additional panic attacks. Agoraphobia is a component of this disorder.
An anxiety disorder characterized by an intense, irrational fear cued by the presence or anticipation of a specific object or situation. Exposure to the phobic stimulus immediately provokes an anxiety response. In adults, the specific phobia is recognized as excessive or unreasonable.
Disruptions of the rhythmic cycle of bodily functions or activities.
A class of traumatic stress disorders that is characterized by the significant dissociative states seen immediately after overwhelming trauma. By definition it cannot last longer than 1 month, if it persists, a diagnosis of post-traumatic stress disorder (STRESS DISORDERS, POST-TRAUMATIC) is more appropriate.
A persistent failure to speak in certain social situations (i.e., school) where speaking is expected, despite speaking in other situations.
A disorder characterized by an impairment in the development of an individual's expressive language which is in contrast to his/her nonverbal intellect and receptive language development. The impairment may be acquired (i.e., due to a brain lesion or head trauma) or developmental (i.e., no known neurological insult).
A disorder characterized by an impairment in the development of an individual's expressive and receptive language capabilities which is in contrast to his/her nonverbal intellect. The impairment may be acquired (i.e., due to a brain lesion or head trauma) or developmental (i.e., no known neurological insult).
Includes two similar disorders: oppositional defiant disorder and CONDUCT DISORDERS. Symptoms occurring in children with these disorders include: defiance of authority figures, angry outbursts, and other antisocial behaviors.
A category of psychiatric disorders which include disorders related to the taking of a drug of abuse (including alcohol, prescribed medications and recreational drugs).
Disorders stemming from the misuse and abuse of alcohol.
A category of psychiatric disorders characterized by the presence of psychotic symptoms such as delusions or hallucinations or negative symptoms such as affective flattening.
A category of psychiatric disorders characterized by a disturbance in sexual desire and in the psychophysiological changes that make up the sexual response cycle.
A cystic teratoma that arises from the ovary. It presents as a cystic mass that contains sebaceous material admixed with hairs. In a minority of cases it is bilateral.
A cystic lesion that arises from the ovary. It is characterized by the presence of cystic spaces that contain fluid and a solid tissue component.
Uterus tilted backward and folded over on itself.
Clinical evidence of disease resulting from mental and/or behavioral dysfunction.
Without a stable or permanent residence.
Sexual assault is any sexual activity to which you haven't freely given your consent. This includes completed or attempted sex acts that are against your will. Sometimes it can involve a victim who is unable to consent. It also includes abusive sexual contact. It can happen to men, women or children. The attacker can be anyone - a current or former partner, a family member, a person in position of power or trust, a friend, an acquaintance, or a stranger. Sexual assault can affect your health in many ways. It can lead to long-term health and emotional problems. It is important to seek help if you have been assaulted. First, get to a safe place. Then dial 9-1-1 or go to a hospital for medical care. You may want to have counseling to deal with your feelings. The most important thing to know is that the assault was not your fault. Centers for Disease Control and Prevention.
Failing to produce an effect from some foregoing stimulus or agent.
Stridor is a high pitched sound resulting from turbulent air flow in the upper airway.
The hydrochloride salt form of apomorphine, a derivative of morphine and non-ergoline dopamine agonist with high selectivity for dopamine D2, D3, D4 and D5 receptors. Apomorphine hydrochloride acts by stimulating dopamine receptors in the nigrostriatal system, hypothalamus, limbic system, pituitary gland, and blood vessels. This enhances motor function, suppresses prolactin release, and causes vasodilation and behavioral effects. Apomorphine hydrochloride is used in the treatment of Parkinson's disease and erectile dysfunction. In addition, apomorphine hydrochloride acts on the chemoreceptor trigger zone and is used as a central emetic in the treatment of drug overdose.
The sodium salt form of phenytoin, a hydantoin derivate and non-sedative antiepileptic agent with anticonvulsant activity. Phenytoin sodium promotes sodium efflux from neurons located in the motor cortex, thereby stabilizing the neuron and inhibiting synaptic transmission. This leads to a reduction in posttetanic potentiation at synapses, an inhibition of repetitive firing of action potentials and ultimately inhibits the spread of seizure activity.
Daydreaming dominated by unconscious material and primary processes for the purpose of wish fulfillment or to alleviate social isolation.
Immunological states where the immune system produces harmful responses upon reexposure to sensitising antigens.
Apparent movement of a fixated light in a dark field.
Refers to the loss of the outer layer of the epidermis in large, scale-like flakes.
Physiological disturbances in normal sexual performance in either the male or the female.
An abscess that is located in the abdominal cavity posterior to the peritoneum.
AIDS related research with a minimum of 20% (or $100,000) research efforts related to children 0-18 years of age. To include: Pregnant women, Neonates, Infants
A malignant neoplasm arising from the glandular epithelium of the appendix with invasion of the appendiceal wall beyond the muscularis mucosa. The majority of cases are well differentiated adenocarcinomas with mucinous stroma formation. Clinically, it may present as an abdominal mass or with symptoms of acute appendicitis. Patients with chronic ulcerative colitis are at a higher risk in developing appendiceal adenocarcinomas compared to the general population.
A syndrome associated with damage to the spinal cord above the mid thoracic level (see SPINAL CORD INJURIES) characterized by a marked increase in the sympathetic response to minor stimuli such as bladder or rectal distention. Manifestations include HYPERTENSION; TACHYCARDIA (or reflex bradycardia); FEVER; FLUSHING; and HYPERHIDROSIS. Extreme hypertension may be associated with a STROKE. (From Adams et al., Principles of Neurology, 6th ed, pp538 and 1232; J Spinal Cord Med 1997;20(3):355-60)
An adenocarcinoma that arises from the Bartholin gland. Subtypes include papillary and mucinous adenocarcinoma.
A carcinoma that arises from the extrahepatic bile ducts. The majority are adenocarcinomas.
A congenital anomaly characterized by the presence of two bladders.
Botulism that is caused by contact with spores of Clostridial bacteria, which subsequently grow in the intestine and release toxin.
A tumor arising from the ependymal lining of the ventricles.
A benign, malignant, or borderline circumscribed biphasic neoplasm that arises from the breast. It usually affects middle-aged women. It is characterized by the presence of a double layer of epithelial cells that are arranged in clefts, surrounded by a spindle cell mesenchymal (stromal) component.
A benign, circumscribed and usually encapsulated lesion of the breast. It contains all the components of the breast tissue.
A rare malignant tumor of the breast, affecting mostly older men. It accounts for less than 1% of all malignancies in men. The most common histologic type is invasive ductal carcinoma. Most patients are treated with mastectomy. -- 2004
A benign papillary neoplasm that arises anywhere in the ductal system of the breast. It is characterized by fibrovascular structures lined by benign epithelial and myoepithelial proliferations. Intraductal breast papillomas are classified as central, when they arise in large ducts, or peripheral, when they arise in the terminal ductal lobular units.
Hypertrophic cardiomyopathy with an symmetrical and concentric pattern of hypertrophy.
Ab abnormal connection between a carotid artery and the cavernous sinus.
Inflammation of the blood vessels within the brain.
Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease characterized by infantile-onset diarrhea, childhood-onset cataract, adolescent- to young adult-onset tendon xanthomas, and adult-onset progressive neurologic dysfunction (dementia, psychiatric disturbances, pyramidal and/or cerebellar signs, dystonia, atypical parkinsonism, peripheral neuropathy, and seizures). Chronic diarrhea from infancy may be the earliest clinical manifestation. In approximately 75% of affected individuals, cataracts are the first finding, often appearing in the first decade of life. Xanthomas appear in the second or third decade; they occur on the Achilles tendon, the extensor tendons of the elbow and hand, the patellar tendon, and the neck tendons. Xanthomas have been reported in the lung, bones, and central nervous system. Some individuals show cognitive impairment from early infancy, whereas the majority have normal or only slightly impaired intellectual function until puberty; dementia with slow deterioration in intellectual abilities occurs in the 20s in more than 50% of individuals. Neuropsychiatric symptoms such as behavioral changes, hallucinations, agitation, aggression, depression, and suicide attempts may be prominent. Pyramidal signs (i.e., spasticity) and/or cerebellar signs almost invariably become evident between ages 20 and 30 years. The biochemical abnormalities that distinguish CTX from other conditions with xanthomas include high plasma and tissue cholestanol concentration, normal-to-low plasma cholesterol concentration, decreased chenodeoxycholic acid, increased concentration of bile alcohols and their glyconjugates, and increased concentrations of cholestanol and apolipoprotein B in cerebrospinal fluid.
A subtype of MICROSCOPIC COLITIS, characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. Microscopic examination of biopsy samples taken from the COLON show larger-than-normal band of subepithelial COLLAGEN.
Heart disease which occurs as a result of a primary pulmonary disease. Cor pulmonale most often manifests as right ventricular hypertrophy; it can also lead to right ventricular failure.
Blockage of an artery due to passage of a clot (THROMBUS) from a systemic vein to a systemic artery without its passing through the lung which acts as a filter to remove blood clots from entering the arterial circulation. Paradoxical embolism occurs when there is a defect that allows a clot to cross directly from the right to the left side of the heart as in the cases of ATRIAL SEPTAL DEFECTS or open FORAMEN OVALE. Once in the arterial circulation, a clot can travel to the brain, block an artery, and cause a STROKE.
An acute, usually bacterial infection affecting the endometrium. It is characterized by the presence of neutrophils or microabscesses in the endometrial glands. Symptoms include fever, lower abdominal pain, and vaginal discharge.
A non-granulomatous or granulomatous chronic inflammation of the endometrium. Causes include sexually transmitted pathogens and gynecological procedures. Patients may present with irregular bleeding.
Esophagitis resulting from exposure to herpes virus.
A benign smooth muscle neoplasm arising from the lower part of the esophagus. It is the most common mesenchymal neoplasm of the esophagus. Dysphagia is a frequent clinical symptom.
The occurrence of the full-thickness tear (perforation) of the wall of the esophagus.
The state of being a eunuch, a male without TESTES or whose testes failed to develop. It is characterized by the lack of mature male GERM CELLS and TESTICULAR HORMONES.
An acquired coagulation disorder characterized by the partial or complete absence of factor XIII activity in the blood.
A carcinoma arising from the fallopian tube. Most patients are postmenopausal, and postmenopausal bleeding is the most frequently seen symptom. Morphologically, the majority of fallopian tube carcinomas are serous or endometrioid adenocarcinomas.
A fulminating bacterial infection of the deep layers of the skin and FASCIA. It can be caused by many different organisms, with STREPTOCOCCUS PYOGENES being the most common.
An abnormal communication between the terminus of a coronary artery, bypassing the myocardial capillary bed and entering any segment of the systemic or pulmonary circulation.
An abnormal communication between a bronchus and the pleural cavity.
A polypoid epithelial neoplasm that arises from the gallbladder. According to the neoplastic growth pattern, it is classified as tubular, tubulopapillary, or papillary.
A carcinoma of the oral cavity that arises from the upper or lower gingiva.
Inflammation of a specific segment of glomeruli, which is associated with subacute bacterial endocarditis, and frequently produces microscopic hematuria without azotemia.
A malignant soft tissue neoplasm that arises from the heart.
Accumulation of blood in the EPIDURAL SPACE between the SKULL and the DURA MATER, often as a result of bleeding from the MENINGEAL ARTERIES associated with a temporal or parietal bone fracture. Epidural hematoma tends to expand rapidly, compressing the dura and underlying brain. Clinical features may include HEADACHE; VOMITING; HEMIPARESIS; and impaired mental function.
A condition characterized by the presence of a variant of normal hemoglobin (hemoglobin E), which is caused by mutation(s) in the gene encoding the beta subunit of the hemoglobin molecule.
Sporadic inclusion body myositis (IBM) is the most common age-related muscle disease in the elderly that results in severe disability. Although traditionally considered an inflammatory myopathy, it is now considered to be more consistent with a myodegenerative disease (Sugarman et al., 2002; Askanas and Engel, 2006).
A carcinoma arising from the small intestine. The vast majority are adenocarcinomas. The remaining cases are adenosquamous, squamous, or undifferentiated carcinomas.
A benign smooth muscle neoplasm arising from the small intestine. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
Gastrointestinal stromal tumors are mesenchymal tumors found in the gastrointestinal tract that originate from the interstitial cells of Cajal, the pacemaker cells that regulate peristalsis in the digestive tract. Approximately 70% of GISTs develop in the stomach, 20% in the small intestine, and less than 10% in the esophagus, colon, and rectum. GISTs are typically more cellular than other gastrointestinal sarcomas. They occur predominantly in patients who are 40 to 70 years old but in rare cases may occur in younger persons (Miettinen et al., 1999, 1999). GISTs can also be seen in neurofibromatosis-1 (NF1; 162200) due to mutations in the NF1 gene, and are thus distinct from the GISTs described here. Sandberg and Bridge (2002) reviewed the cytogenetics and molecular genetics of gastrointestinal stromal tumors. Coffey et al. (2007) reviewed the clinical features, pathogenesis, and molecular treatments of Menetrier disease (137280) and GIST, both of which are hyperproliferative disorders of the stomach caused by dysregulated receptor tyrosine kinases.
A developmental defect in which a kidney is located in an abnormal anatomic position.
A usually aggressive malignant neoplasm arising from the kidney. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
An abnormality of the normal developmental rotation of the kidney leading to an abnormal orientation of the kidney.
A sudden immune response occurring after transplantation, directed against donor kidney alloantigens.
A condition in which plasma cells secrete immunoglobulin light chains of only one type, kappa or lambda. Light chain deposition disease is often associated with multiple myeloma or lymphoproliferative disease, but as many as 50% of patients have no evidence of neoplastic plasma cell proliferation. Light chains excreted in the urine are known as Bence Jones protein. Amyloidosis and severe renal failure occur more frequently than in multiple myeloma. Also known as Bence Jones myeloma. L-chain disease, L-chain myeloma, and LCDD. --2004
A congenital vascular malformation in the liver composed of masses of blood vessels that are atypical or irregular in arrangement and size.
The spread of a carcinoma to the lung. This may be from a primary lung carcinoma, or from a carcinoma at a distant anatomic site.
Extensive infiltration of the lymphatic vessels by cancer cells, resulting in widespread cancer dissemination. The lymphatic vessels appear as palpable, cord-like structures, especially in skin areas overlying the carcinoma.
Primary lymphedema is caused by anatomic or functional defects in the lymphatic system, resulting in chronic swelling of body parts. There may be accompanying nail and skin changes, such as nail dysplasia or papillomatosis. Onset is usually at birth or in early childhood but can occur later, and the severity is variable (summary by Gordon et al., 2013 and Balboa-Beltran et al., 2014). For a discussion of the genetic heterogeneity of lymphocytic malformation, see 153100.
A neurodegenerative condition that is characterized by demyelination or necrosis of the CORPUS CALLOSUM. Symptoms include DEPRESSION; PARANOIA; DEMENTIA; SEIZURES; and ATAXIA which can progress to COMA and death in a few months. Marchiafava-Bignami syndrome is seen often in alcoholics but has been found in non-alcoholics as well.
Mucolipidosis IV is characterized by severe psychomotor delay evident by the end of the first year of life and slowly progressive visual impairment during the first decade as a result of a combination of corneal clouding and retinal degeneration. By the end of the first decade of life and certainly by their early teens, all individuals with typical mucolipidosis IV have severe visual impairment as a result of retinal degeneration. Neurodegeneration is thought to occur in no more than 15% of individuals. About 5% of individuals have atypical mucolipidosis IV, often manifest as less severe psychomotor retardation and/or eye findings. Although in the past, mucolipidosis IV was considered an Ashkenazi Jewish disease, currently most affected individuals are non-Ashkenazi Jewish.
An autosomal dominant degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles. (Neuromuscul Disord 1997;7(1):55-62; Adams et al., Principles of Neurology, 6th ed, p1420)
Narrowing of a tear duct (lacrimal duct).
Chronic inflammation of the kidney affecting the interstitium of the kidneys surrounding the tubules.
Nephropathy secondary to sickle cell disease, characterized by the presence of sickled erythrocytes in the renal medullary vessels, renal ischemia and microinfarctions, renal papillary necrosis, and renal tubular abnormalities.
Neuropathy that is caused by inadequate blood supply.
A neoplasm that arises from the ovary and originates from germ cells. Representative examples include teratoma, embryonal carcinoma, yolk sac tumor, and dysgerminoma.
A circumscribed area of pus or necrotic debris in the parenchyma of the pancreas.
A cystic adenocarcinoma that arises from the pancreas. It includes the acinar cell and serous cystadenocarcinoma subtypes.
A disorder characterized by recurrent episodes of pancreatitis that start at a young age. It is caused by mutations in the PRSS1 or SPINK1 genes. Patients are at a high risk of developing pancreatic carcinoma.
A squamous cell carcinoma arising from the penis. It occurs chiefly in the squamous epithelium of the glans, coronal sulcus, and foreskin. Etiologic factors include phimosis, lichen sclerosus, smoking, ultraviolet irradiation, history of warts or condylomas, and lack of circumcision. Human papilloma virus is present in a subset of penile squamous cell carcinomas. Patients may present with an exophytic or flat ulcerative mass in the glans or a large primary tumor with inguinal nodal and skin metastases. Morphologic variants include the basaloid carcinoma, warty (condylomatous) carcinoma, verrucous carcinoma, and sarcomatoid (spindle cell) carcinoma. (WHO, 2004)
A malignant soft tissue neoplasm that arises from the penis. Representative examples include Kaposi sarcoma, leiomyosarcoma, and angiosarcoma.
Hyperkalemic periodic paralysis (hyperPP) is characterized by attacks of flaccid limb weakness (which may also include weakness of the muscles of the eyes, throat, and trunk), hyperkalemia (serum potassium concentration >5 mmol/L) or an increase of serum potassium concentration of at least 1.5 mmol/L during an attack of weakness and/or provoking/worsening of an attack by oral potassium intake, normal serum potassium between attacks, and onset before age 20 years. Although the absence of paramyotonia (muscle stiffness aggravated by cold and exercise) was originally postulated as a means of distinguishing hyperPP from paramyotonia congenita (PMC), approximately 45% of individuals with hyperPP have paramyotonia. In approximately half of affected individuals, attacks of flaccid muscle weakness begin in the first decade of life, with 25% reporting their first attack at age ten years or older. Initially infrequent, the attacks then increase in frequency and severity over time until approximately age 50 years, after which the frequency of attacks declines considerably. Potassium-rich food or rest after exercise may precipitate an attack. A cold environment and emotional stress provoke or worsen the attacks. A spontaneous attack commonly starts in the morning before breakfast, lasts for 15 minutes to one hour, and then disappears. Cardiac arrhythmia or respiratory insufficiency usually does not occur during attacks. Between attacks, approximately half of individuals with hyperPP have mild myotonia (muscle stiffness) that does not impede voluntary movements. More than 80% of individuals with hyperPP older than 40 years report permanent muscle weakness and about one third develop a chronic progressive myopathy.
Hypokalemic periodic paralysis (hypoPP) is a condition in which affected individuals may experience paralytic episodes with concomitant hypokalemia (serum potassium <3.5 mmol/L). The paralytic attacks are characterized by decreased muscle tone (flaccidity) more marked proximally than distally with normal to decreased deep tendon reflexes. The episodes develop over minutes to hours and last several minutes to several days with spontaneous recovery. Some individuals have only one episode in a lifetime; more commonly, crises occur repeatedly: daily, weekly, monthly, or less often. The major triggering factors are cessation of effort following strenuous exercise and carbohydrate-rich evening meals. Additional triggers can include cold, stress/excitement/fear, salt intake, prolonged immobility, use of glucosteroids or alcohol, and anesthetic procedures. The age of onset of the first attack ranges from two to 30 years; the duration of paralytic episodes ranges from one to 72 hours with an average of nearly 24 hours. Long-lasting interictal muscle weakness may occur in some affected individuals and in some stages of the disease and in myopathic muscle changes. A myopathy may occur independent of paralytic symptoms and may be the sole manifestation of hypoPP.
Pneumoconiosis caused by exposure to talc. It is characterized by fibrosis and granulomatous changes in the lung parenchyma. Chest x-rays reveal diffuse lung opacities and pleural abnormalities.
Interstitial lung disease (ILD), or pneumonitis, is a heterogeneous group of disorders characterized pathologically by expansion of the interstitial compartment of the lung by inflammatory cells. Fibrosis occurs in many cases (Visscher and Myers, 2006). Desquamative interstitial pneumonitis (DIP) was originally described as a pathologic entity by Liebow et al. (1965). Lung biopsy shows diffuse and uniform filling of alveoli by clusters of cells which Liebow et al. (1965) speculated to be 'desquamated pneumocytes.' Since then, these cells have been shown primarily to be pigmented alveolar macrophages. Other features include thickened alveolar septa with an infiltrate of inflammatory cells and plump, cuboidal type II pneumocytes. Mild collagen deposition without architectural distortion or honeycombing may be present. Different forms of ILD represent pathologic classifications based on histologic patterns rather than clinical diagnoses and may occur in a variety of clinical contexts (Visscher and Myers, 2006). See also usual interstitial pneumonitis (UIP; see 178500), which is associated with pulmonary fibrosis. Although DIP occurs most often as a sporadic disorder in adults during the third to fifth decade of life and is highly associated with smoking (Carrington et al., 1978), reports of a familial form with onset in infancy and early death suggest a genetic basis (Sharief et al., 1994). Cases of DIP reported in infants are often more severe and refractory to treatment than those reported in adults (Nogee et al., 2001). With the advent of molecular genetic analysis, some cases of familial early-onset respiratory insufficiency associated with a pathologic diagnosis of DIP have been shown to result from congenital dysfunction of surfactant metabolism (see, e.g., SMDP1, 265120) due to mutations in genes involved in surfactant metabolism (Nogee et al., 2001; Whitsett and Weaver, 2002).
A rare malignant soft tissue neoplasm that arises from the prostate gland. Representative examples include leiomyosarcoma, rhabdomyosarcoma, and stromal sarcoma.
Hermaphroditism refers to a discrepancy between the morphology of the gonads and that of the external genitalia. In female pseudohermaphroditism, the genotype is female (XX) and the gonads are ovaries, but the external genitalia are virilized.
Hermaphroditism refers to a discrepancy between the morphology of the gonads and that of the external genitalia. In male pseudohermaphroditism, the genotype is male (XY) and the external genitalia are imcompletely virilized, ambiguous, or complete female. If gonads are present, they are testes.
A congenital or acquired cardiovascular abnormality characterized by the narrowing of the lumen of the main pulmonary artery or its branches. Signs and symptoms include dyspnea, tachypnea, tachycardia, fatigue, and edema.
Infiltration of smooth muscle-like cells in lymph vessels as well as the lung (pleura, alveolar septa, bronchi, pulmonary vessels and lymphatics as well as lymph nodes, especially in posterior mediastinum and retroperitoneum). Focal emphysema can develop because of airway narrowing, and the thoracic duct may be obliterated. Pulmonary lymphangiomyomatosis may lead to multiple small cysts with a hamartomatous proliferation of smooth muscle in their walls.
An autosomal recessive disorder caused by loss-of-function mutation(s) in the CTSK gene, encoding cathepsin K, an enzyme involved in bone resorption by osteoclasts. This condition is characterized by some or all of the following: osteosclerosis, short stature, pituitary hypoplasia with growth hormone deficiency, and cerebral demyelination.
An acute necrotic infection of the SCROTUM; PENIS; or PERINEUM. It is characterized by scrotum pain and redness with rapid progression to gangrene and sloughing of tissue. Fournier gangrene is usually secondary to perirectal or periurethral infections associated with local trauma, operative procedures, or urinary tract disease.
broad term used to describe several different acute conditions occurring with sickle cell disease, including aplastic crisis, hemolytic crisis, and vasoocclusive crisis.
An ependymoma that arises from the spinal cord.
A rare benign smooth muscle neoplasm arising from the wall of the stomach. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern. Unlike gastrointestinal stromal tumors, gastric leiomyomas are by definition negative for CD34 and CD117 (C-KIT).
A malignant germ cell neoplasm arising from the testis. It is composed of primitive epithelial cells arranged in solid, papillary, and glandular configurations. Most patients present with a testicular mass, which may be associated with pain. More than half of the patients have metastatic disease at diagnosis. The form of treatment following radical orchiectomy is stage dependent.
A malignant germ cell tumor arising from the testis. It represents the rarest of the testicular germ cell tumors. Histologically it is characterized by the presence of syncytiotrophoblasts and cytotrophoblasts.
A non-seminomatous germ cell tumor arising from the testis. It is characterized by the presence of various tissues which correspond to the different germinal layers (endoderm, mesoderm, and ectoderm). According to the level of differentiation of the tissues which comprise the tumor, testicular teratomas are classified as mature or immature. Mature teratomas are composed of well differentiated, adult-type tissues. Immature teratomas are composed of immature, fetal type-tissues. Testicular teratomas in children follow a benign clinical course whereas in postpubertal patients may metastasize to other anatomic sites.
Formation or presence of a blood clot (THROMBUS) in the CAVERNOUS SINUS of the brain. Infections of the paranasal sinuses and adjacent structures, CRANIOCEREBRAL TRAUMA, and THROMBOPHILIA are associated conditions. Clinical manifestations include dysfunction of cranial nerves III, IV, V, and VI, marked periorbital swelling, chemosis, fever, and visual loss. (From Adams et al., Principles of Neurology, 6th ed, p711)
The formation of a thrombus in the renal vein.
A primary carcinoma of the thyroid gland composed of undifferentiated cells. The malignant cells demonstrate evidence of epithelial differentiation, either by immunohistochemistry or electron microscopic studies. Microscopically, in the majority of cases there is a mixture of spindle, epithelioid, and giant cells. The vast majority of the patients present with a rapidly enlarging neck mass. The clinical course is usually aggressive.
A neuroendocrine carcinoma arising from the C-cells of the thyroid gland. It is closely associated with multiple endocrine neoplasia syndromes. Approximately 10% to 20% of medullary thyroid carcinomas are familial. Patients usually present with a thyroid nodule that is painless and firm. In the majority of cases nodal involvement is present at diagnosis. Surgery is the preferred treatment for both primary lesions and recurrences. This carcinoma is generally not very sensitive to radiation and almost unresponsive to chemotherapy.
Nonmedullary thyroid cancer (NMTC) comprises thyroid cancers of follicular cell origin and accounts for more than 95% of all thyroid cancer cases. The remaining cancers originate from parafollicular cells (medullary thyroid cancer, MTC; 155240). NMTC is classified into 4 groups: papillary, follicular (188470), Hurthle cell (607464), and anaplastic. Approximately 5% of NMTC is hereditary, occurring as a component of a familial cancer syndrome (e.g., familial adenomatous polyposis, 175100; Carney complex, 160980) or as a primary feature (familial NMTC or FNMTC). Papillary thyroid cancer (PTC) is the most common histologic subtype of FNMTC, accounting for approximately 85% of cases (summary by Vriens et al., 2009). PTC is characterized by distinctive nuclear alterations including pseudoinclusions, grooves, and chromatin clearing. PTCs smaller than 1 cm are referred to as papillary microcarcinomas. These tumors have been identified in up to 35% of individuals at autopsy, suggesting that they may be extremely common although rarely clinically relevant. PTC can also be multifocal but is typically slow-growing with a tendency to spread to lymph nodes and usually has an excellent prognosis (summary by Bonora et al., 2010). Genetic Heterogeneity of Susceptibility to Nonmedullary Thyroid Cancer Other susceptibilities to nonmedullary thyroid cancer include NMTC2 (188470), caused by mutation in the SRGAP1 gene (606523); NMTC3 (606240), mapped to chromosome 2q21; NMTC4 (616534), caused by mutation in the FOXE1 gene (602617); and NMTC5 (616535), caused by mutation in the HABP2 gene (603924). A susceptibility locus for familial nonmedullary thyroid carcinoma with or without cell oxyphilia (TCO; 603386) has been mapped to chromosome 19p.
A benign adipose tissue neoplasm of the tongue.
Transient erythroblastopenia of childhood is a pure red cell aplasia that occurs in a previously healthy child, most commonly between 6 months and 4 years of age. The course is characterized by a complete recovery, usually within 1 to 2 months after diagnosis. In most cases no therapy is necessary, although some children may need red cell transfusion (summary by Gustavsson et al., 2002).
A rare congenital abnormality resulting in the URETER passing dorsal to and being obstructed by the INFERIOR VENA CAVA.
Prolapse of the urethral mucosa from the exterior urethral opening.
A developmental abnormality characterized by the presence of an obstructing membrane in the posterior urethra of the male newborn. It results in bladder obstruction.
A morphologic variant of adenocarcinoma affecting the vagina. It is characterized by the presence of malignant glandular epithelium and clear cells containing glycogen.
A squamous cell carcinoma arising from the vagina. Human papillomavirus infection is associated with the development of vaginal intraepithelial neoplasia and invasive squamous cell carcinoma. Signs and symptoms include painless bleeding, postcoital bleeding, and urinary tract symptoms. Morphologically it resembles squamous cell carcinomas in other anatomic sites. Radiation therapy is the preferred treatment for most cases. The prognosis is related to the stage of the disease.
A malignant mesenchymal neoplasm that arises from the vagina. Representative examples include botryoid-type embryonal rhabdomyosarcoma, leiomyosarcoma, and endometrioid stromal sarcoma.
A malignant mesenchymal neoplasm that arises from the vulva. Representative examples include childhood botryoid-type embryonal rhabdomyosarcoma, alveolar soft part sarcoma, and leiomyosarcoma.
The anterior abdominal wall is sunken and presents a concave rather than a convex contour.
An incomplete closure of the abdominal wall.
The absence of all phalanges of all the digits of a limb and the associated soft tissues.
An increased concentration of an amino acid in the urine.
Pain in and around the anus or rectum (perianal region).
Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the ankle.
An abnormality of coagulation related to a decreased concentration of antithrombin-III.
An abnormal localized widening (dilatation) of the aortic root.
A localized pathological or traumatic structural change, damage, deformity, or discontinuity of bone.
A laboratory test result indicating abnormally high numbers of megakaryocytes in the bone marrow.
Orange or yellow discoloration of the skin caused by excessive deposits of carotene.
An abnormal reduction in the ability to masticate (chew), i.e., in the ability to crush and ground food in preparation for swallowing.
Pain in the jaw or ear induced by chewing or otherwise moving the jaw.
The presence of small (ca. 0.5-1.0 mm) dilated blood vessels near the surface of the mucous membranes of the conjunctiva.
A conical projection of the anterior or posterior surface of the lens, occurring as a developmental anomaly.
A cough accompanied by expectorated secretions.
Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults).
Coxa vara includes all forms of decrease of the femoral neck shaft angle (the angle between the neck and the shaft of the femur) to less than 120 degrees.
A type of crying in an abnormally high-pitched voice.
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
Painful sensation in the external ear region.
A question about whether an individual has experienced early satiety.
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
An electrocardiographic finding in which the T wave appears increased in amplitude and cresting at a point.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the elbow.
A sensation of tightness in the elbow joint when attempting to move it, especially after a period of inactivity.
Bleeding originating from the esophagus.
Blockage of the normal flow of the contents in the esophagus.
An abnormal accumulation of fluid beneath the skin of the legs.
Reddening of the palmar and plantar regions of the body with occasional involvement of the distal extremities.
A sensation of discomfort emanating from the humerus or its supporting structures.
Absence (due to failure to form) or underdevelopment of the extremities.
Redness of the skin of the eyelids, caused by hyperemia of the capillaries in the lower layers of the skin.
The facial appearance is more circular than usual as viewed from the front. [pmid:19125436]
Redness of the skin of the face, caused by hyperemia of the capillaries in the lower layers of the skin. [HPO:probinson]
Fasciculations or fibrillation affecting the tongue muscle.
Mild fever that does not exceed 38.5 degree centrigrade.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the finger.
A sensation of tightness in a finger joint when attempting to move it, especially after a period of inactivity.
Enlargement of the soft tissues of one or more fingers.
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased sensation of itching over the skin of the foot.
An abnormally increased height of the forehead.
A hemangioma arising from any part of the digestive system.
A clinical term that indicates the presence of a white patch on the surface of the gum which cannot be characterized as any other disease. It may be a precancerous condition and in most cases histologic examination reveals keratosis.
Painful sensation in the gingival region.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the groin region.
A lesser degree of hair pigmentation than would otherwise be expected.
An abnormal hand posture in which the hands are clenched to fists. All digits held completely flexed at the metacarpophalangeal and interphalangeal joints.
Muscular atrophy involving the muscles of the hand.
Reduced strength of the musculature of the hand.
An unintentional, oscillating to-and-fro muscle movement affecting the hand.
A very rare and usually lethal autosomal recessive inherited disorder of the skin caused by mutations in the ABCA12 gene. It is characterized by the presence of hard and thick skin. There are diamond-like plates formed in the skin which are separated by fissures.
An unintentional, oscillating to-and-fro muscle movement affecting head movement.
An elevation above the normal ratio of the volume of red blood cells to the total volume of blood.
Microscopic hematuria detected by dipstick or microscopic examination of the urine.
An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements.
A laboratory test result indicating an abnormal amount of fetal hemoglobin in a biological sample.
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
The examiner applies firm but persistent pressure over the liver for 10 seconds while observing the mean jugular venous pressure. Normally there is either no rise or only a transient (i.e., 2 to 3 sec) rise in mean jugular venous pressure. A sustained increase in the mean venous pressure until abdominal compression is released is abnormal and indicates impaired right heart function. This abnormal response is called hepatojugular reflux.
A sensation of tightness in the hip joint when attempting to move it, especially after a period of inactivity.
A condition in which albumin level in blood (SERUM ALBUMIN) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (ALBUMINURIA).
An abnormally increased level of immunoglobulin A in blood.
An abnormally decreased level of immunoglobulin IgM in blood. [HPO:probinson]
Lack of strength of the intercostal muscles, i.e., of the muscle groups running along the ribs that create and move the chest wall.
An abnormal structure or form of the joints, i.e., one or more of the articulations where two bones join.
A sensation of tightness in the knee joint when attempting to move it, especially after a period of inactivity.
A benign exophytic neoplasm that arises from the larynx, usually the true vocal cords. It is related to human papillomavirus infection and may arise as a single or multiple lesions. It is characterized by the presence of a connective tissue core covered by stratified squamous epithelium. Hoarseness is the presenting symptom. Transformation to carcinoma is rare.
Any white discoloration of the nails or nail plates.
A severe crack in a lip. A lip fissure may be painful, may bleed and often is a recurring manifestation.
Enlargement of the lip typically due to fluid buildup or inflammation.
A space-occupying pathologic process that affects the liver parenchyma.
An increased tendency to fractures of the long bones (Mainly, the femur, tibia, fibula,humerus, radius, and ulna).
Abnormally anterior positioning of the infraorbital and perialar regions, or increased convexity of the face, or increased nasolabial angle. The midface includes the maxilla, the cheeks, the zygomas, and the infraorbital and perialar regions of the face
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
A mass present in the mediastinal space.
Decreased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD below mean. Alternatively, an apparently decreased maximum width of tooth.
Abnormally small sized handwriting defined formally as an impairment of a fine motor skill manifesting mainly as a progressive or stable reduction in amplitude during a writing task. [HPO:probinson, PMID:29403348]
A clinical term that indicates the presence of a white patch on the mucous membrane in the mouth which cannot be characterized as any other disease. It may be a precancerous condition and in most cases histologic examination reveals keratosis.
A facial appearance characterized by a permanently or nearly permanently opened mouth.
A hemangioma arising from the mucous membranes.
Blood clot formed within muscle tissue following leakage of blood into the tissue.
Swelling due to an accumulation of excessive fluid in the neck.
Decreased strength of the neck musculature.
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
Increased volume and globular shape of the anteroinferior aspect of the nose.
A form of nystagmus in which the eyeball makes rotary motions around the axis.
Swelling related to fluid accumulation within the palate.
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased sensation of itching over the palm(s) of the hand.
An abnormal laboratory test result in which the partial thromboplastin time is found to be greater than the control value. As a possible indicator of coagulopathy, a prolonged partial thromboplastin time (PTT) may occur in a variety of diseases and disorders, both primary and related to treatment.
Muscular atrophy affecting the muscles that attach to the pelvic girdle (the gluteal muscles, the lateral rotators, adductor magnus, adductor brevis, adductor longus, pectineus, and gracilis muscles).
Pelvic girdle pain is experienced between the posterior iliac crest and the gluteal fold, in particular in the sacroiliac joint. The pain may radiate to the posterior thigh. The condition is generally related to pregnancy, trauma, arthritis and osteoarthritis.
Length of penis more than 2 SD below the mean for age accompanied by hypospadias.
The presence of a rash (change of color and texture) of the perianal skin.
Compression of the heart caused by rigid, thickened, or fused pericardial membranes.
A noticeable change in a person's behavior and thinking. Causes include depression, drug or alcohol abuse, brain injuries, brain tumors, and Alzheimer's disease.
An abnormal accumulation of fluid beneath the skin on sole of the foot.
An increased level of renin (PRO:000013883) in the blood.
A non-Hodgkin or Hodgkin lymphoma that arises in the cerebral hemispheres as a primary lesion.
A premonitory symptom or early warning sign of a mental or physical disorder.
An acute or chronic infectious process affecting the prostate gland.
Formation of membrane-like structures consisting of coagulated exudate that is loosely adherent to an inflamed tissue.
Abnormal breath sounds (crackles) heard on auscultation only in the bases of the lungs. They indicate inflammation, fluid, or infection in the air sacs of the lung.
The presence of a fistula between the perineum and the rectum.
Fluid which has escaped from retinal blood vessels with a high concentration of lipid, protein, and cellular debris with a typically bright, reflective, white or cream colored appearance on the surface of the retina.
Necrotizing VASCULITIS of small and medium size vessels, developing as a complication in RHEUMATOID ARTHRITIS patients. It is characterized by peripheral vascular lesions, cutaneous ULCERS, peripheral GANGRENE, and MONONEURITIS MULTIPLEX.
Congenital vertical talus (CVT), also known as 'rocker-bottom foot' deformity, is a dislocation of the talonavicular joint characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence (summary by Levinsohn et al., 2004). The condition is transmitted in an autosomal dominant pattern of inheritance, and sometimes shows incomplete penetrance and variable expressivity. There may be a broad spectrum of deformities, including flatfoot, talipes equinovarus (TEV or clubfoot), cavus foot, metatarsus adductus, and even hypoplasia of the tibia (summary by Dobbs et al., 2006).
The patient stands with the feet placed together and balance and is asked to close his or her eyes. A loss of balance upon eye closure is a positive Romberg sign and is interpreted as indicating a deficit in proprioception.
Of or pertaining to the country as opposed to the city. (American Heritage Dictionary)
An excessive desire to eat salt (sodium chloride) or salty foods.
Painful sensation in the skin covering the top and the back of the head.
Abnormal protrusion of the scapula away from the surface of the back.
Yellowing of the white part of the eyes, often due to a rise in bilirubin levels.
Incoordination of movement caused by a deficit in the sensory nervous system. Sensory ataxia can be distinguished from cerebellar ataxia by asking the patient to close his or her eyes. Persons with cerebellar ataxia show only a minimal worsening of symptoms, whereas persons with sensory ataxia show a marked worsening of symptoms.
Increased level of circulating 4-androstenedione.
Decreased concentration of ceruloplasmin in the blood.
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase, CPK; EC 2.7.3.2) in the blood. CPK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
A reduction below normal concentration of estradiol in the circulation.
Abnormally reduced concentration of ferritin, a ubiquitous intracellular protein that stores iron, in the blood.
Abnormal raised concentration of ferritin, a ubiquitous intracellular protein that stores iron, in the blood. [HPO:probinson]
Shoulder joint stiffness is a perceived sensation of tightness in shoulders when attempting to move them after a period of inactivity.
The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls.
A sensation of dermal stinging or heat, not necessarily accompanied by redness or physical signs of skin irritation.
A condition in which the skin can be stretched beyond normal, and then returns to its initial position.
An area of hardness in the skin. Causes include inflammatory process and infiltration of the skin by malignant neoplasms.
Pinhead size (3 mm) skin discolorization due to hemorrhage.
A large (greater than 5-10 mm) raised skin lesion with a wide, flat surface.
A circumscribed and elevated skin lesion filled with purulent material.
Formation of new tissue formed in the healing of a wound.
Laminar thickening of skin. [HPO:sdoelken]
Subjective impression of increased softness upon palpitation of the skin.
Skin that splits easily with minimal injury.
A type of primitive reflex that is elicited by tapping the upper lip lightly. The contraction of the muscles causes the mouth to resemble a snout [NCBI Books:NBK395].
A height above that which is expected according to age and gender norms.
Inflammed tongue with hyperplastic (enlarged) fungiform papillae that is said to resemble a strawberry or raspberry. [PMID:26222562]
Reduced volume of the testicle (the male gonad).
An elevated circulating testosterone level in the blood.
A thumb with three phalanges in a single, proximo-distal axis. Thus, this term applies if the thumb has an accessory phalanx, leading to a digit like appearance of the thumb.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the toe.
Wasting of the tongue. [ORCID:0000-0001-5208-3432]
A clinical term that indicates the presence of a white patch on the surface of the tongue which cannot be characterized as any other disease. It may be a precancerous condition and in most cases histologic examination reveals keratosis.
Tongue extending beyond the alveolar ridges or teeth at rest.
A reduction in the strength of the trunk muscles.
Divergence of the longitudinal axis of the hand at the wrist in a posterior (ulnar) direction (i.e., towards the little finger).
An increased concentration of catecholamine in the urine.
An uncomfortable feeling of itching and burning in the vaginal opening resulting from inadequate vaginal lubrication. It is commonly seen during and after menopause, childbirth, or stressful conditions. It results in painful intercourse.
Any structural abnormality of a cardiac valve.
Loss of peripheral vision with retention of central vision, resulting in a constricted circular tunnel-like field of vision.
An abnormal increase in the pitch (frequency) of the voice.
Vomiting of material that is of fecal origin.
Repetitive loss and regain of body weight.
A sensation of tightness in the wrist joint when attempting to move it, especially after a period of inactivity.
Excretion of non-amino organic acids in urine.
Unlocalized atrophy of the brain with decreased total brain matter volume and increased ventricular size.
A record of a patient's background regarding health and disease events of blood relatives. A patient's family medical history may be important in diagnosing existing conditions.
Benign familial hematuria is an autosomal dominant condition manifest as nonprogressive isolated microscopic hematuria that does not result in renal failure. It is characterized pathologically by thinning of the glomerular basement membrane (GBM), and can be considered the mildest end of the spectrum of renal diseases due to type IV collagen defects of the basement membrane. The most severe end of the spectrum is represented by Alport syndrome (301050; 203780, 104200), which results in end-stage renal failure and may be associated with hearing loss and ocular anomalies (review by Lemmink et al. (1996)).
A chronic self-perpetuating hepatocellular INFLAMMATION of unknown cause, usually with HYPERGAMMAGLOBULINEMIA and serum AUTOANTIBODIES.
A less severe form of mania characterized by elevated mood, hyperactivity, and grandiosity. In contrast to mania, these symptoms do not cause significant impairment of the individual's productivity at work, or social and family relationships.
A benign renal neoplasm composed of fat, vascular, and smooth muscle elements.
A deficit in equilibrium, which may manifest as unsteady ambulation or inability to maintain an upright position.
Extensive interstitial fibrosis with alveolar disruption and bronchiolectasis.
A type of vulvar cancer that originates from melanocytes of the vulva.
A spectrum of inflammation involving the female upper genital tract and the supporting tissues. It is usually caused by an ascending infection of organisms from the endocervix. Infection may be confined to the uterus (ENDOMETRITIS), the FALLOPIAN TUBES; (SALPINGITIS); the ovaries (OOPHORITIS), the supporting ligaments (PARAMETRITIS), or may involve several of the above uterine appendages. Such inflammation can lead to functional impairment and infertility.
Jaundice occurring as a result of red blood cell rupture.
A decrease in the amount of oxygen in the body. Symptoms range from mild (impaired judgment, memory loss, impaired motor coordination) to severe (seizures and coma).
A white crystalline carbohydrate, typically sucrose, used as a sweetener and preservative.
The absence of or defect in the perception of colors.
Abnormal narrowing of the coronary artery.
Terminology associated with the employment status codelist of the Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM).
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
A rare neuromuscular disorder with onset usually in late childhood or early adulthood, characterized by intermittent or continuous widespread involuntary muscle contractions; FASCICULATION; hyporeflexia; MUSCLE CRAMP; MUSCLE WEAKNESS; HYPERHIDROSIS; TACHYCARDIA; and MYOKYMIA. Involvement of pharyngeal or laryngeal muscles may interfere with speech and breathing. The continuous motor activity persists during sleep and general anesthesia (distinguishing this condition from STIFF-PERSON SYNDROME). Familial and acquired (primarily autoimmune) forms have been reported. (From Ann NY Acad Sci 1998 May 13;841:482-496; Adams et al., Principles of Neurology, 6th ed, p1491)
Fibrous dysplasia/McCune-Albright syndrome (FD/MAS), the result of an early embryonic postzygotic somatic activating pathogenic variant in GNAS (encoding the cAMP pathway-associated G-protein, Gsa), is characterized by involvement of the skin, skeleton, and certain endocrine organs. However, because Gsa signaling is ubiquitous, additional tissues may be affected. Café au lait skin macules are common and are usually the first manifestation of the disease, apparent at or shortly after birth. Fibrous dysplasia (FD), which can involve any part and combination of the craniofacial, axial, and/or appendicular skeleton, can range from an isolated, asymptomatic monostotic lesion discovered incidentally to severe disabling polyostotic disease involving practically the entire skeleton and leading to progressive scoliosis, facial deformity, and loss of mobility, vision, and/or hearing. Endocrinopathies include: Gonadotropin-independent precocious puberty resulting from recurrent ovarian cysts in girls and autonomous testosterone production in boys; Testicular lesions with or without associated gonadotropin-independent precocious puberty; Thyroid lesions with or without non-autoimmune hyperthyroidism; Growth hormone excess; FGF23-mediated phosphate wasting with or without hypophosphatemia in association with fibrous dysplasia; and Neonatal hypercortisolism. The prognosis for individuals with FD/MAS is based on disease location and severity.
The hydrochloride salt form of flurazepam, a member of the benzodiazepines and a long-acting depressor of the central nervous system (CNS) with sedative and hypnotic effects. Flurazepam binds to a specific site on the benzodiazepine-gamma-aminobutyric acid (GABA)-A-chloride ionophore receptor complex located on the neuronal membrane. Binding causes an allosteric modification of the receptor thereby enhancing the affinity of GABA to the receptor leading to an increase in the frequency of chloride-channel opening events, which leads to an increase in chloride ion conductance, neuronal hyperpolarization, inhibition of the action potential, and a decrease in neuronal excitability. By modulating binding of the GABA inhibitory neurotransmitter to GABA-A receptors in the ascending reticular activating system, flurazepam blocks arousal of the cortical and limbic system, thereby exerting its sedative and hypnotic effect.
Bacterial infection of the hair follicle and the surrounding skin. It is caused by Staphylococcus aureus. It presents as a painful, erythematous and swollen skin lesion.
A clonal disorder characterized by the secretion of a mu heavy chain that lacks a variable region. Most patients present with slowly progressive chronic lymphocytic leukemia (CLL). In contrast to most cases of CLL, Mu heavy chain disease is associated with hepatosplenomegaly and absence of lymphadenopathy. --2004
An abnormality in the of lipid metabolism.
The permanent lack of SEXUAL DEVELOPMENT in an individual. This defect is usually observed at an age after expected PUBERTY.
An uncommon cause of hypopituitarism seen after severe postpartum hemorrhaging. Prolonged hypovolemia leads to ischemic necrosis of the pituitary. Clinical signs typically present in the puerperium and include failure to begin lactation, fatigue, hypotension and eventual amenorrhea. Clinical course is usually mild, however extreme cases may progress to adrenal failure. Prognosis is most favorable when hormone replacement is initiated soon after symptom onset.
A pituitary functional deficit affecting all the anterior pituitary hormones (growth hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, adrenocorticotropic hormone, and prolactin).
A disorder characterized by the persistent or recurrent inability to achieve or to maintain an erection during sexual activity.
existing at, and usually before, birth; referring to conditions that are present at birth, regardless of their causation; inborn metabolism disorders are generally not treed here.
A neoplasm with neuroendocrine differentiation that arises from the pancreas. It includes neuroendocrine tumors (low and intermediate grade) and neuroendocrine carcinomas (high grade).
4-hydroxyquinaldate, a metabolite of tryptophan secreted in urine.
A primary or metastatic malignant neoplasm involving the lung.
Joint inflammation, most often affecting large joints, associated with Lyme disease, presenting months after infection.
Age-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. The vision loss usually becomes noticeable in a person's sixties or seventies and tends to worsen over time.Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected, but reduced dim light (scotopic) vision often occurs in the early stages of the disease.Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and vision loss that worsens slowly over time. The condition typically affects vision in both eyes, although vision loss often occurs in one eye before the other.The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly. This form of the condition is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted.
An abnormal occlusion where some of the mandibular teeth are buccal to the maxillary teeth.
Treacher Collins syndrome (TCS) is characterized by bilateral and symmetric downslanting palpebral fissures, malar hypoplasia, micrognathia, and external ear abnormalities. Hypoplasia of the zygomatic bones and mandible can cause significant feeding and respiratory difficulties. About 40%-50% of individuals have conductive hearing loss attributed most commonly to malformation of the ossicles and hypoplasia of the middle ear cavities. Inner ear structures tend to be normal. Other, less common abnormalities include cleft palate and unilateral or bilateral choanal stenosis or atresia. Typically intellect is normal.
A class of synthetic chemicals/drugs similar to opiates (opium derivatives) with analgesic properties. Due to binding to opiate receptors, opioids mimic opiate activity on neurons, various cells (i.e. lymphocytes), pain suppression and other neurobehavioral activity. (NCI)
A benign, well circumscribed soft tissue neoplasm characterized by the presence of spindle shaped myofibroblasts and mast cells in a collagenous stroma.
A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.
Accumulation of chyle (the whitish fluid taken up by the lacteals in the intestine, consisting of an emulsion of lymph and triglyceride fat thatpasses into the veins by the thoracic duct) in the pericardium. Chylopericardium is generally caused by obstruction of or trauma to the thoracic duct.
Any kind of inflammatory process of the tonsils, pharynx, or/and larynx characterized by pain in swallowing.
The hydrochloride salt form of phenoxybenzamine, a synthetic, dibenzamine alpha-adrenergic antagonist with antihypertensive and vasodilatory properties. Phenoxybenzamine non-selectively and irreversibly blocks the postsynaptic alpha-adrenergic receptor in smooth muscle, thereby preventing vasoconstriction, relieving vasospasms, and decreasing peripheral resistance. Reflex tachycardia may occur and may be enhanced by blockade of alpha-2 receptors which enhances norepinephrine release. Phenoxybenzamine is reasonably anticipated to be a human carcinogen.
The hydrochloride salt form of the d-isomer of synthetic diphenyl propionate derivative propoxyphene, with narcotic analgesic effect. This agent mimics the effects of the endogenous opiate dextropropoxyphene, by binding to mu receptors located throughout the central nervous system. The binding results in GTP to GDP exchanges on the mu-G-protein complex, by which effector adenylate cyclase is inactivated thereby decreasing intracellular cAMP. This, in turn, inhibits the release of various nociceptive neurotransmitters, such as substance P, gamma-aminobutyric acid (GABA), dopamine, acetylcholine, noradrenaline, vasopressin, and somatostatin. In addition, dextropropoxyphene closes N-type voltage-gated calcium channels and opens calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization, thereby reducing neuronal excitability, which further decreases the perception of pain.
Lower urinary tract symptom, such as slow urinary stream, associated with PROSTATIC HYPERPLASIA in older men.
A transient inflammatory pulmonary disorder characterized by eosinophilia. Eosinophilic infiltration of the lungs may be secondary to parasitic infection or drug hypersensitivity. Clinical signs include dry cough, fever and dyspnea. Prognosis is favorable as the disorder follows a self-limited course.
Disorder occurring at the site of insertion of tendons or ligaments into bones or joint capsules
Abnormally rapid heartbeats caused by reentrant conduction over the accessory pathways between the HEART ATRIA and the HEART VENTRICLES. The impulse can also travel in the reverse direction, as in some cases, atrial impulses travel to the ventricles over the accessory pathways and back to the atria over the BUNDLE OF HIS and the ATRIOVENTRICULAR NODE.
The maleate salt form of triethylperazine, a piperazine phenothiazine derivative and a dopamine antagonist used as antiemetic. Thiethylperazine blocks postsynaptic dopamine 2 (D2) receptors in the medullary chemoreceptor trigger zone (CTZ), thereby decreasing stimulation of the vomiting center in the brain. Peripherally, thiethylperazine blocks the vagus nerve in the gastrointestinal tract. In addition, this agent also shows antagonistic activities mediated through muscarinic receptors, H1-receptors, and alpha(1)-receptors.
an inflammation of the thyroid gland that frequently results in hypothyroidism (lowered thyroid function)
The maleate salt form of trimipramine, a tricyclic secondary amine of the dibenzazepine class, with an antidepressant property. Trimipramine maleate appears to inhibit serotonin transport and norepinephrine uptake by nerve terminals. This increases available norepinephrine or serotonin and prolongs its action.
A biochemical abnormality referring to an elevation of BLOOD UREA NITROGEN and CREATININE. Azotemia can be produced by KIDNEY DISEASES or other extrarenal disorders. When azotemia becomes associated with a constellation of clinical signs, it is termed UREMIA.
A synthetic, intermediate-acting mono-quaternary steroid and non-depolarizing neuromuscular blocking agent, with muscle relaxant activity. Vecuronium competitively binds to and blocks the nicotinic acetylcholine receptor at the neuromuscular junction, thereby preventing acetylcholine (ACh) binding and resulting in skeletal muscle relaxation and paralysis. Vecuronium has a shorter duration of action than pancuronium.
A rapid, multivectorial, conjugate, involuntary eye movement, without an intersaccadic interval.
A hereditary immunodeficiency disorder caused by the absence of major histocompatibility complex class II expression. Signs include upper and lower respiratory tract bacterial infections, malabsorption, diarrhea, and mucocutaneous candidiasis.
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies. [DDD:wouwehand]
Evidence for remaining tumor following primary treatment that is only apparent using highly sensitive techniques.
Rare, autosomal recessive disorder caused by deficiency of the beta 2 integrin receptors (RECEPTORS, LEUKOCYTE-ADHESION) comprising the CD11/CD18 family of glycoproteins. The syndrome is characterized by abnormal adhesion-dependent functions, especially defective tissue emigration of neutrophils, leading to recurrent infection.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Diseases of animals within the order PRIMATES. This term includes diseases of Haplorhini and Strepsirhini.
Diseases of chimpanzees, gorillas, and orangutans.
A disorder caused by a spinal injury leading to an incomplete spinal lesion. Patients develop paralysis, ataxia and loss of sensation. Causes include spinal cord tumors, spinal traumas, ischemia, and inflammatory processes affecting the spine.
A condition that is caused by recurring atheroembolism in the lower extremities. It is characterized by cyanotic discoloration of the toes, usually the first, fourth, and fifth toes. Discoloration may extend to the lateral aspect of the foot. Despite the gangrene-like appearance, blue toes may respond to conservative therapy without amputation.
An indolent, extranodal type of non-Hodgkin lymphoma composed of small B-lymphocytes (centrocyte-like cells). The gastrointestinal tract is the most common site of involvement. Other common sites of involvement include lung, head and neck, ocular adnexae, skin, thyroid, and breast. Gastric involvement is associated with the presence of H. pylori infection. (WHO, 2001)
The passage of a substance or infectious agent from the mother to the fetus or newborn.
The transmission of infectious disease or pathogens from one individual to another.
Vaccines or candidate vaccines designed to prevent SAIDS; (SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME); and containing inactivated SIMIAN IMMUNODEFICIENCY VIRUS or type D retroviruses or some of their component antigens.
An abnormality of coagulation related to a decreased concentration of vitamin K-dependent protein S. Protein S is a cofactor of protein C.
A placenta that fails to be expelled after BIRTH of the FETUS. A PLACENTA is retained when the UTERUS fails to contract after the delivery of its content, or when the placenta is abnormally attached to the MYOMETRIUM.
Vegetative state refers to the neurocognitive status of individuals with severe brain damage, in whom physiologic functions (sleep-wake cycles, autonomic control, and breathing) persist, but awareness (including all cognitive function and emotion) is abolished.
Non-therapeutic positive end-expiratory pressure occurring frequently in patients with severe airway obstruction. It can appear with or without the administration of external positive end-expiratory pressure (POSITIVE-PRESSURE RESPIRATION). It presents an important load on the inspiratory muscles which are operating at a mechanical disadvantage due to hyperinflation. Auto-PEEP may cause profound hypotension that should be treated by intravascular volume expansion, increasing the time for expiration, and/or changing from assist mode to intermittent mandatory ventilation mode. (From Harrison's Principles of Internal Medicine, 12th ed, p1127)
Impairment of the left ventricle to either fill or eject adequately.
Decrease, loss, or removal of the mineral constituents of bones. Temporary loss of bone mineral content is especially associated with space flight, weightlessness, and extended immobilization. OSTEOPOROSIS is permanent, includes reduction of total bone mass, and is associated with increased rate of fractures. CALCIFICATION, PHYSIOLOGIC is the process of bone remineralizing. (From Dorland, 27th ed; Stedman, 25th ed; Nicogossian, Space Physiology and Medicine, 2d ed, pp327-33)
Disorder characterized by nausea, vomiting, and dizziness, possibly in response to vestibular disorientation or fluid shifts associated with space flight. (From Webster's New World Dictionary)
Drugs used for their effects on serotonergic systems. Among these are drugs that affect serotonin receptors, the life cycle of serotonin, and the survival of serotonergic neurons.
Any agent that binds to and blocks dopamine receptors.
Drugs used for their actions on histaminergic systems. Included are drugs that act at histamine receptors, affect the life cycle of histamine, or affect the state of histaminergic cells.
An abnormal increase in the amount of oxygen in the tissues and organs.
Impairment of the right ventricular function associated with low ejection fraction and decreased motility of the right ventricular wall.
A pharmaceutical agent that is categorized by its ability to alter the progression of autoimmune disease.
The presence of parasites (especially malarial parasites) in the blood. (Dorland, 27th ed)
A form of organizing pneumonia with a non-infectious etiology. Excessive proliferation of granulation tissue occurs in alveolar ducts and alveoli and primarily causes injury to alveolar walls, but bronchioles may be affected.
A passage or transfer, as of a disease from one individual to another.
The pharmacological result, either desirable or undesirable, of drugs interacting with components of the diet. (From Stedman, 25th ed)
A fetal/maternal condition that is risky and portends complications for the mother and/or fetus, when compared to a normal pregnancy.
Any neoplasms of the male breast. These occur infrequently in males in developed countries, the incidence being about 1% of that in females.
The historic designation for scrofula (TUBERCULOSIS, LYMPH NODE). The disease is so called from the belief that it could be healed by the touch of a king. This term is used only for historical articles using the name ""king's evil"", and is to be differentiated from scrofula as lymph node tuberculosis in modern clinical medicine. (From Webster, 3d ed)
A clinical condition characterized by fever and profuse sweating and associated with high mortality. It occurred in epidemic form five times in the fifteenth and sixteenth centuries in England, first in 1485 and last in 1551, specially during the summer and early autumn, attacking the relatively affluent adult male population. The etiology was unknown.
Autosomal dominant neovascular inflammatory vitreoretinopathy is a blinding disorder that shares some clinical features with retinitis pigmentosa (see 268000), uveitis, and proliferative diabetic retinopathy (see 603933). Features include prominent ocular inflammation; vascular dropout, large spots of hyperpigmentation, and neovascularization of the peripheral and posterior retina; vitreous hemorrhage; and retinal detachment (summary by Sheffield et al., 1992).
A congenital anomaly with a narrowing or complete absence of the opening between the right ventricle and the pulmonary artery.
Laceration or tearing of the VENTRICULAR SEPTUM, usually caused by MYOCARDIAL INFARCTION.
Any agent that binds to and inhibits adrenergic receptors.
Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of ACETYLCHOLINE, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of MUSCARINIC AGONISTS, although most modern texts discourage that usage.
Any agent that is capable of activating cholinergic receptors (nicotinic and muscarinic) or of enhancing or prolonging the actions of acetylcholine.
Any agent that binds to and blocks nicotinic and/or muscarinic receptors, thereby preventing the actions of the neurotransmitter acetylcholine (Ach) at these receptors.
Drugs that bind to but do not activate CHOLINERGIC RECEPTORS, thereby blocking the actions of ACETYLCHOLINE or cholinergic agonists.
Substances used for their pharmacological actions on GABAergic systems. GABAergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.
Drugs used for their actions on any aspect of excitatory amino acid neurotransmitter systems. Included are drugs that act on excitatory amino acid receptors, affect the life cycle of excitatory amino acid transmitters, or affect the survival of neurons using excitatory amino acids.
Substances used for their pharmacological actions on glycinergic systems. Glycinergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.
Gases or volatile liquids that vary in the rate at which they induce anesthesia; potency; the degree of circulation, respiratory, or neuromuscular depression they produce; and analgesic effects. Inhalation anesthetics have advantages over intravenous agents in that the depth of anesthesia can be changed rapidly by altering the inhaled concentration. Because of their rapid elimination, any postoperative respiratory depression is of relatively short duration. (From AMA Drug Evaluations Annual, 1994, p173)
Ultrashort-acting anesthetics that are used for induction. Loss of consciousness is rapid and induction is pleasant, but there is no muscle relaxation and reflexes frequently are not reduced adequately. Repeated administration results in accumulation and prolongs the recovery time. Since these agents have little if any analgesic activity, they are seldom used alone except in brief minor procedures. (From AMA Drug Evaluations Annual, 1994, p174)
A structurally and mechanistically diverse group of drugs that are not tricyclics or monoamine oxidase inhibitors. The most clinically important appear to act selectively on serotonergic systems, especially by inhibiting serotonin reuptake.
Drugs that bind to and activate excitatory amino acid receptors.
Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.
Agents that are used to treat bipolar disorders or mania associated with other affective disorders.
A pharmacological agent that protects the central nervous system from damage caused by acute ischemia or chronic neurodegenerative diseases.
Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms.
Infections with viruses of the order MONONEGAVIRALES. The concept includes FILOVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; and RHABDOVIRIDAE INFECTIONS.
Infections with viruses of the family FILOVIRIDAE. The infections in humans consist of a variety of clinically similar viral hemorrhagic fevers but the natural reservoir host is unknown.
A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.
The structure of one molecule that imitates or simulates the structure of a different molecule.
Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.
Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.
Drugs used in the treatment of movement disorders. Most of these act centrally on dopaminergic or cholinergic systems. Among the most important clinically are those used for the treatment of Parkinson disease (ANTIPARKINSON AGENTS) and those for the tardive dyskinesias.
Natural or synthetic compounds inhibiting acetylcholine neurotransmitter action at nicotinic receptors, which are ionotropic receptors that form ligand-gated ion channels in cells' plasma membranes.
A generalized state of dysregulated inflammation induced by noninfectious processes. It is characterized by two or more of the following signs and symptoms: fever or hypothermia, increased heart rate, increased respiratory rate, and abnormal white blood cell count.
Impairment of the ventricle to either fill or eject adequately.
Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).
Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.
Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.
Agents or remedies that historically have produced stimulation or excited functional activity.
Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.
An abnormal, increased fatiguability of the musculature.
Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.
Idiopathic environmental intolerance (IEI) formerly called multiple chemical sensitivity, is a subjective illness marked by recurrent, nonspecific symptoms attributed to low levels of chemical, biologic or physical agents.
Mild form of HFRS rarely hemorrhagic and seldom fatal. Caused by the PUUMALA VIRUS.
Any infection caused by a virus of the genus Hantavirus, which is transmitted by aerosolized rodent excreta or rodent bites, that can result in a variety of clinical manifestations from hemorrhagic fever with renal syndrome to a pulmonary syndrome.
Inability to achieve and maintain an erection (ERECTILE DYSFUNCTION) due to defects in the arterial blood flow to the PENIS, defect in venous occlusive function allowing blood drainage (leakage) from the erectile tissue (corpus cavernosum penis), or both.
An abscess located in the abdominal cavity, i.e., the cavity between the diaphragm above and the pelvis below. (From Dorland, 27th ed)
Encephalitis resulting from viral infection.
Monoclonal antibodies (MoAb) conjugated with radioisotopes, i.e., I-131, Y-90, T-99, or In-111. Using radioimmunoconjugates in radiotherapy or radioimaging has the advantage of targeting cells carrying specific antigens, thereby limiting toxic effects on normal cells. Tumor eradication can be achieved by either the antibody-mediated immune response or by only the cytotoxic activity of the radiation.
An agent that consists of an immune substance, such as a monoclonal antibody, antigen or an immunoglobulin, and covalently bound to other molecule(s), usually either a toxin, a radioisotope, or a cytotoxic agent. Immunoconjugates allow for specific delivery of certain substances to specific cells or tissues for diagnostic or therapeutic purposes.
Acute respiratory illness in humans caused by the SIN NOMBRE VIRUS whose primary rodent reservoir is the deer mouse Peromyscus maniculatus. First identified in the southwestern United States, this syndrome is characterized most commonly by fever, myalgias, headache, cough, and rapid respiratory failure.
Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.
A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
Drugs that act principally at one or more sites within the peripheral neuroeffector systems, the autonomic system, and motor nerve-skeletal system. (From Smith and Reynard, Textbook of Pharmacology, 1991, p75)
Any abnormality of the cardiovascular system.
Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.
Congenital structural abnormalities of the mouth and jaws, including the dentition.
Drugs that act on neuronal sensory receptors resulting in an increase, decrease, or modification of afferent nerve activity. (From Smith and Reynard, Textbook of Pharmacology, 1991, p367)
Incomplete or underdevelopment of a tissue or organ.
The result of an examination or inquiry.
Catalysis of a biochemical reaction at physiological temperatures. In biologically catalyzed reactions, the reactants are known as substrates, and the catalysts are naturally occurring macromolecular substances known as enzymes. Enzymes possess specific binding sites for substrates, and are usually composed wholly or largely of protein, but RNA that has catalytic activity (ribozyme) is often also regarded as enzymatic. [GOC:vw, ISBN:0198506732]
Used with chemicals, drugs, and endogenous substances to indicate substances or agents that have affinity for a receptor and intrinsic activity at that receptor. (From Textbook of Pharmacology, 1991, p.16)
The sodium salt of docusate, a dioctyl salt and an emollient laxative with stool-softening activity. Docusate decreases surface tension and emulsification of fecal matter and allows water to penetrate and mix with stool. As a result, it softens the stool.
A phenolic phytochemical naturally occurring in extra virgin olive oil, with potential antioxidant, anti-inflammatory and cancer preventive activities. Although the mechanisms of action through which hydroxytyrosol exerts its effects have yet to be fully determined, this agent affects the expression of various components of the inflammatory response, possibly through the modulation of the nuclear factor-kappa B (NF-kB) pathway. The effects include the modulation of pro-inflammatory cytokines, such as the inhibition of interleukin-1alpha (IL-1a), IL-1beta, IL-6, IL-12, and tumor necrosis factor-alpha (TNF-a); increased secretion of the anti-inflammatory cytokine IL-10; inhibition of the production of certain chemokines, such as C-X-C motif chemokine ligand 10 (CXCL10/IP-10), C-C motif chemokine ligand 2 (CCL2/MCP-1), and macrophage inflammatory protein-1beta (CCL4/MIP-1b); and inhibition of the expression of the enzymes inducible nitric oxide synthase (iNOS/NOS2) and prostaglandin E2 synthase (PGES), which prevent the production of nitric oxide (NO) and prostaglandin E (PGE2), respectively. In addition, hydroxytyrosol is able to regulate the expression of other genes involved in the regulation of tumor cell proliferation, such as extracellular signal-regulated and cyclin-dependent kinases. Also, hydroxytyrosol scavenges free radicals and prevents oxidative DNA damage. This induces apoptosis and inhibits proliferation in susceptible cancer cells.
A synthetic thiacetic acid derivative used in biomedical research, carcinogenic Pirinixic acid is a peroxisome proliferator that activates specific peroxisome proliferator-activated receptors (PPAR). PPARs play an important role in diverse cellular functions, including lipid metabolism, cell proliferation, differentiation, adipogenesis, and inflammatory signaling. (NCI04)
A second-generation sulfonamide derivative with antihyperglycemic activity. Like other sulfonylureas, glipalamide exerts extra-pancreatic activity, such as increased binding of insulin to insulin receptors on adipocytes.
Substances that inhibit the action of Protein Kinase A, causing disruption of a protein phosphorylation cascade in certain signal transduction pathways.
A chloroethylnitrosourea derivative that inhibits proliferation and growth of tumor cells by alkylation and cross-linkage of DNA strands of tumor cells. (NCI)
A drug that may protect healthy cells from chemotherapy and radiation without inhibiting the effects of these therapies on tumor cells.
benzene derivatives with chlorine substituted at one or more positions.
A selective benzothiophene estrogen receptor modulator (SERM). Raloxifene binds to estrogen receptors (ER) as a mixed estrogen agonist/antagonist; it displays both an ER-alpha-selective partial agonist/antagonist effect and a pure ER-beta-selective antagonist effect. This agent functions as an estrogen agonist in some tissues (bones, lipid metabolism) and as an estrogen antagonist in others (endometrium and breasts), with the potential for producing some of estrogen's beneficial effects without producing its adverse effects. (NCI04)
A tripeptidic nitrogen mustard compound and bifunctional alkylating agent with antineoplastic activity.
A water-soluble phosphate ester prodrug of phenytoin, a hydantoin derivative with anticonvulsant activity. Fosphenytoin is hydrolyzed to phenytoin by phosphatases. Phenytoin exerts its effect mainly by promoting sodium efflux and stabilizes neuronal membranes in the motor cortex. This leads to a suppression of excessive neuronal firing and limits the spread of seizure activity.
The amino acid analog fluorodopa (FDOPA) labeled with fluorine F 18, a positron-emitting isotope, with potential tumor tracer property. Fluorine F 18 fluorodopa is able to cross the blood-brain barrier and is taken up by brain tumor cells. As uptake is higher in tumor cells, tumors may then be imaged using positron emission tomography (PET). Assessing tumor uptake of FDOPA may be beneficial for diagnosis, localization and in determining further treatment.
A non-glycosylated form of interferon beta-1 that has a serine at position 17. It is used in the treatment of both RELAPSING-REMITTING MULTIPLE SCLEROSIS and CHRONIC PROGRESSIVE MULTIPLE SCLEROSIS.
The tert-butylamine salt of perindopril, the ethyl ester of a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Upon hydrolysis, perindopril erbumine is converted to its active form perindoprilat, inhibiting ACE and the conversion of angiotensin I to angiotensin II; consequently, angiotensin II-mediated vasoconstriction and angiotensin II-stimulated aldosterone secretion from the adrenal cortex are inhibited and diuresis and natriuresis ensue.
A quinoline-3-carboxamide with potential antineoplastic activity. Roquinimex inhibits endothelial cell proliferation, migration, and basement membrane invasion; reduces the secretion of the angiogenic factor tumor necrosis factor alpha by tumor-associated macrophages (TAMs); and inhibits angiogenesis. This agent is also an immune modulator that appears to alter cytokine profiles and enhance the activity of T cells, natural killer cells, and macrophages. (NCI04)
A nicotinic acid derivative with diuretic activity. Triflocin inhibits the sodium-bicarbonate symporter in the proximal convoluted tubules.
An anthrapyrazole-based antineoplastic antibiotic. Losoxantrone intercalates into DNA, induces single- and double-stranded DNA breaks and inhibits topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Losoxantrone is less cardiotoxic than doxorubicin.
A recombinant human nonglycosylated interleukin-1 (IL-1) receptor antagonist with potential antineoplastic activity. Anakinra binds to the IL-1 receptor, thereby blocking the binding of the IL-1 to and activation of its receptor. Blockade of IL-1 activity may inhibit the cascade of downstream pro-angiogenic factors such as vascular endothelial cell growth factor, tumor necrosis factor-alpha, and IL-6, resulting in inhibition of tumor angiogenesis. (NCI04)
A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity.
A selective ADRENERGIC BETA-2 RECEPTOR agonist that functions as a BRONCHODILATOR when administered by inhalation. It is used to manage the symptoms of ASTHMA and CHRONIC OBSTRUCTIVE PULMONARY DISEASE.
A drug used to treat depression and peripheral neuropathy (pain, numbness, tingling, burning, or weakness in the hands or feet) that can occur with diabetes. It is also being studied in the treatment of peripheral neuropathy caused by certain anticancer drugs. Cymbalta increases the amount of certain chemicals in the brain that help relieve depression and pain. It is a type of serotonin and norepinephrine reuptake inhibitor.
The orally active fumarate salt of the benzimidazole derivative liarozole with potential antineoplastic activity. As a retinoic acid metabolism blocking agent (RAMBA), liarozole inhibits cytochrome P450-dependent all-trans-retinoic acid (ATRA)-4-hydroxylase, resulting in an increase in endogenous ATRA production, inhibition of cell proliferation, and induction of cell differentiation. This agent also inhibits aromatase, the enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis.
The sodium salt of a synthetic lipid-lowering agent with potential antineoplastic activity. Fluvastatin competitively inhibits hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent lowers plasma cholesterol and lipoprotein levels, and modulates immune responses through the suppression of MHC II (major histocompatibility complex II) on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. Through the inhibition of mevalonate synthesis, statins, like fluvastatin, have been shown to inhibit the production of dolichol, geranylpyrophosphate (GPP) and farnesylpyrophosphate (FPP) and the isoprenylation of the intracellular G-proteins Ras and Rho, which may result in antiangiogenic, apoptotic, and antimetastatic effects in susceptible tumor cell populations.
A 5-hydroxytryptamine-3 (5-HT3) receptor antagonist with antiemetic activity. RG 12915 binds to and antagonizes the action of serotonin on the 5-HT-3 receptor located on vagal afferents in the chemoreceptor trigger zone (CTZ), resulting in suppression of chemotherapy-induced nausea and vomiting.
A benzophenone and nitrophenol compound that acts as an inhibitor of CATECHOL O-METHYLTRANSFERASE, an enzyme involved in the metabolism of DOPAMINE and LEVODOPA. It is used in the treatment of PARKINSON DISEASE in patients for whom levodopa is ineffective or contraindicated.
A semi-synthetic, second-generation taxane derived from a compound found in the European yew tree, Taxus baccata. Docetaxel displays potent and broad antineoplastic properties; it binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell- cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and displays immunomodulatory and pro-inflammatory properties by inducing various mediators of the inflammatory response. Docetaxel has been studied for use as a radiation-sensitizing agent. (NCI04)
A nonsteroidal inhibitor of estrogen synthesis with antineoplastic activity. As a third-generation aromatase inhibitor, letrozole selectively and reversibly inhibits aromatase, which may result in growth inhibition of estrogen-dependent breast cancer cells. Aromatase, a cytochrome P-450 enzyme localized to the endoplasmic reticulum of the cell and found in many tissues including those of the premenopausal ovary, liver, and breast, catalyzes the aromatization of androstenedione and testosterone into estrone and estradiol, the final step in estrogen biosynthesis.
A piperidine-propionate derivative and opioid analgesic structurally related to FENTANYL. It functions as a short-acting MU OPIOID RECEPTOR agonist, and is used as an analgesic during induction or maintenance of general anesthesia, following surgery, during childbirth, and in mechanically ventilated patients under intensive care.
A nonsulfonylurea insulin secretagogue belonging to the melgitinide class with hypoglycemic activity. Repaglinide is rapidly absorbed and has a rapid onset and short duration of action. This agent is metabolized in the liver by CYP2C8 and CYP3A4 and its metabolites are excreted in the bile. Repaglinide has a half-life of one hour.
A synthetic pyridinyl bisphosphonate agent. Risedronate binds to hydroxyapatite crystals in bone and inhibits osteoclast-dependent bone resorption Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=256445&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=256445&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1528"" NCI Thesaurus)
An angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Imidaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Imidaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
Tyrosine analog and PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX antagonist that inhibits PLATELET AGGREGATION and is used in the treatment of ACUTE CORONARY SYNDROME.
An arotinoic acid derivative with a morpholine structure in the polar end group with differentiation inducing and antineoplastic activity. Like other retinoic acid agents, mofarotene binds to and activates retinoic acid receptors (RARs), thereby altering the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells. In addition, this agent is able to inhibit melanoma cell motility.
A chimeric fusion protein containing human transforming growth factor alpha (TGF-a) covalently linked to a truncated form of the bacterial toxin Pseudomonas exotoxin A, PE40, with potential antitumor activity. PE40 lacks the cell-binding domain, but retains domains II and III that are involved in membrane translocation and inhibition of protein synthesis in eukaryotic cells. TGF-a moiety of the TP40 immunotoxin binds to and activates epidermal growth factor receptor (EGFR), a tyrosine kinase receptor overexpressed on certain cancer cells. After internalization, the endotoxin moiety of the immunotoxin-receptor complex causes protein synthesis inhibition via modifying translation elongation factor 2 (EF-2), thereby impedes tumor cell growth and proliferation.
A truncated form of the glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 peptide, with GLP-1 receptor (GLP-1R) antagonistic and GLP-1R-mediated signaling inhibiting activities. Upon administration, exendin 9-39 competitively binds to and inhibits the activity of GLP-1R, thereby inhibiting GLP-1/GLP-1R-mediated signaling. This antagonizes the glucagonostatic and the insulinotropic effects of GLP-1. By abrogating GLP-1-mediated simulation of insulin release and reduction of glucagon secretion after food intake, exendin 9-39 may be used to help study the potential effects of overproduction of GLP-1 on food intake, weight loss and glucose levels. GLP-1R, located on pancreatic beta cells, is overexpressed on certain tumor cell types. GLP-1 is a gastrointestinal (GI) and insulinotropic hormone that is released after a meal and plays a key role in the regulation of blood glucose levels.
A highly cytotoxic macrocyclic lactone polyether with antitumor activity. Spongistatin, originally isolated from marine Spongia species, binds to the vinca domain of tubulin, thereby interferes with microtubule assembly and results in inhibition of mitosis. This agent does not affect the binding of colchicine to tubulin, but it was a potent inhibitor of the binding of vinblastine and GTP to tubulin.
A non-nucleoside reverse transcriptase inhibitor. Emivirine has a structure typical of a nucleoside analog but has been shown to bind directly to the reverse transcriptase and act as an NNRTI. However, it is no longer in development due to the fact that it causes an increasingly rapid breakdown of other drugs metabolized by the cytochrome P450 enzyme.
A lipophilic, second-generation, chlorin-based photosensitizer. Upon intravenous administration, HPPH selectively accumulates in the cytoplasm of cancer or pre-cancerous cells. When laser light is applied, a photodynamic reaction between HPPH and oxygen occurs, resulting in the production of cytotoxic free radicals and singlet oxygen and free radical-mediated cell death. Compared to the first-generation photosensitizer porfimer sodium, HPPH shows improved pharmacokinetic properties and causes only mild skin photosensitivity which declines rapidly within a few days after administration.
A benzimidazole derivative and a non-peptide angiotensin II receptor antagonist with antihypertensive property. Telmisartan selectively antagonizes angiotensin II binding to the AT1 subtype receptor, located in vascular smooth muscle and adrenal gland. The antagonism results in vasodilation and inhibits the angiotensin II-mediated aldosterone production, which in turn leading to a decrease in sodium and water as well as an increase in potassium excretion leading to a subsequent reduction in blood pressure.
A prodrug of acyclovir that is used in the treatment of HERPES ZOSTER and HERPES SIMPLEX VIRUS INFECTION of the skin and mucous membranes, including GENITAL HERPES.
A thiazole derivative and inhibitor of XANTHINE OXIDASE that is used for the treatment of HYPERURICEMIA in patients with chronic GOUT.
A synthetic noncalcemic, nonphosphatemic vitamin D analogue. Paricalcitol binds to the vitamin D receptor and has been shown to reduce parathyroid hormone (PTH) levels. This agent also increases the expression of PTEN ('Phosphatase and Tensin homolog deleted on chromosome Ten'), a tumor-suppressor gene, in leukemic cells and cyclin-dependent kinase inhibitors, resulting in tumor cell apoptosis and tumor cell differentiation into normal phenotypes. (NCI04)
A bis-naphthalimide compound with anticancer activity. Bisnafide selectively intercalates guanine-cytosine (GC) rich regions of DNA, thereby interfering with DNA replication machinery and activity of topoisomerase II. As a result, this agent causes potent cytotoxicity.
A nonpeptide angiotensin II receptor antagonist with antihypertensive activity. Forasartan selectively competes with angiotensin II for the binding of the angiotensin II (AT1) receptor subtype 1 in vascular smooth muscle, thereby blocking angiotensin II-mediated vasoconstriction resulting in vascular dilatation. In addition, the antagonistic effect on AT1 in the adrenal gland, prevents angiotensin II-induced stimulation of aldosterone synthesis and secretion by the adrenal cortex. This blocks the effects of aldosterone leading to an increase in sodium excretion and water and eventually a reduction in plasma volume and blood pressure.
A combination formulation of the antibiotic piperacillin and the beta-lactamase inhibitor tazobactam with antibacterial activity. Piperacillin, a broad-spectrum, semisynthetic penicillin, binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall, thereby interfering with the cross-linking of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. As a result, the cell wall is weakened and the cell lyses. Tazobactam, a penicillanic acid sulfone derivative, irreversibly binds to and inhibits bacterial beta-lactamase at or near its active site, thereby preventing the destruction of the beta-lactamase susceptible piperacillin by this bacterial enzyme.
Serpin B5 (375 aa, ~42 kDa) is encoded by the human SERPINB5 gene. This protein plays a role in the regulation of cell movement and in tumor suppression.
A nonbenzodiazepine from the pyrazolopyrimidine class with hypnotic, sedative, anxiolytic, and muscle relaxant properties. Zaleplon interacts with the gamma-aminobutyric acid (GABA) -A receptor, thereby affecting the chloride channel ionophore complex and potentiating the inhibitory effects of GABA. In addition, zaleplon binds selectively to the brain omega-1 receptor situated on the alpha subunit of the GABA-A/chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding.
A benzoic acid-modified form of para-aminosalicylate, an analog of aminobenzoic acid used to treat tuberculosis.
A sulfonamide and pyrimidine derivative that acts as a dual endothelin receptor antagonist used to manage PULMONARY HYPERTENSION and SYSTEMIC SCLEROSIS.
A synthetic amino acid radiolabeled with carbon-11. Acting as a methyl donor, methionine C 11 is incorporated into macromolecules, where it serves as a positron emission tomography (PET) imaging agent for detecting tumors with high rates of protein synthesis.
A quassinoid phytochemical isolated form the plant Brucea antidysenterica with potential antineoplastic activity. (NCI04)
A quassinoid phytochemical isolated from the plant Brucea antidysenterica with potential antineoplastic activity. (NCI04)
A synthetic pyrimidine nucleoside analogue with potential antineoplastic activity. Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, further compromising DNA replication. This agent is relatively resistant to metabolic deactivation by cytidine deaminase. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates necessary for DNA synthesis and is overexpressed in many tumor types.
A synthetic, noncardiotoxic aza-anthracenedione analogue with potential antineoplastic activity. Pixantrone intercalates into DNA and induces topoisomerase II-mediated DNA strand crosslinks, resulting in inhibition of DNA replication and tumor cell cytotoxicity.
A protein tyrosine kinase inhibitor that selectively inhibits EGFR kinase, involved in signaling pathways. (NCI)
A cyclical heptapeptide with anticoagulant activity. Eptifibatide selectively and reversibly binds to and blocks the platelet glycoprotein IIb/IIIa receptor. This prevents the binding of fibrinogen, von Willebrand factor, and other adhesive ligands and leads to an inhibition of platelet aggregation and prevents thrombus development.
A substituted benzoylphenylurea and an analogue of the pesticide diflubenzuron with potential antineoplastic activity. Unlike most of the anti-cancer drugs causing bone marrow suppression, clanfenur stimulates hematopoiesis both in vivo and in vitro.
An interferon beta-1 subtype that has a methionine at position 1, a cysteine at position 17, and is glycosylated at position 80. It functions as an ANTI-VIRAL AGENT and IMMUNOMODULATOR and is used to manage the symptoms of RELAPSING-REMITTING MULTIPLE SCLEROSIS.
A natural biological response modifier (BRM) isolated from bovine reticuloendothelial tissue. Viruzlin may enhance cell-mediated immune response to tumor cells by direct macrophage activation. (NCI04)
A specific biomarker of hypochlorous acid (HClO), the oxidation product of myeloperoxidase (MPO). Under oxidative stress, 3-chlorotyrosine is produced in proteins with tyrosine residues by the strong oxidant HClO. HClO which is formed at sites of inflammation is also the anti-bacterial molecule produced by neutrophils through MPO-catalyzed oxidation. MPO is a heme-containing enzyme secreted by activated neutrophils and monocytes; it is the only enzyme that produces HClO. Therefore, 3-chlorotyrosine can potentially be used to help determine the extent of neutrophilic inflammation.
A naturally occurring, highly mineralized phyllosilicate clay used as a nutritional supplement with mycotoxin binding and protective activities. Upon ingestion prior to each meal, hydrated sodium calcium aluminosilicate is not absorbed by the gastrointestinal tract but rather binds certain food contaminants, including aflatoxin (AF) and fumonisin B1 (FB1), thereby reducing the bioavailability of these substances. Dietary exposure of AF and FB1 has been associated with an increased risk of certain cancers.
A benzazepine derivative and selective HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNELS inhibitor that lowers the heart rate. It is used in the treatment of CHRONIC STABLE ANGINA in patients unable to take BETA-ADRENERGIC BLOCKERS, and in the treatment of HEART FAILURE.
The cryptophycins are a family of 16-membered macrolide antimitotic agents isolated from the cyanobacteria Nostoc sp. The mechanism of anticancer activity of the cryptophycins has been associated with their destabilization of microtubules and induction of bcl-2 phosphorylation leading to apoptosis. Cryptophycins demonstrated activity against the wide spectrum of solid tumors including those that overexpress the multidrug resistance efflux pump P-glycoprotein. (NCI)
A conjugate consisting of keyhole-limpet hemocyanin (KLH) and fluorescein isothiocyanate (FITC) with potential immunostimulating activity. Vaccination with KLH-FITC may elicit an immune response against fluorescein and the production of anti-fluorescein IgG antibodies. KLH, a natural protein isolated from the marine mollusk keyhole limpet, is an immunostimulant carrier protein.
A sulfonamide derivative and adrenergic alpha-1 receptor antagonist that is used to relieve symptoms of urinary obstruction caused by BENIGN PROSTATIC HYPERPLASIA.
A synthetic imidazole bisphosphonate analog of pyrophosphate with anti-bone-resorption activity. A third-generation bisphosphonate, zoledronic acid binds to hydroxyapatite crystals in the bone matrix, slowing their dissolution and inhibiting the formation and aggregation of these crystals. This agent also inhibits farnesyl pyrophosphate synthase, an enzyme involved in terpenoid biosynthesis. Inhibition of this enzyme prevents the biosynthesis of isoprenoid lipids, donor substrates of farnesylation and geranylgeranylation during the post-translational modification of small GTPase signalling proteins, which are important in the process of osteoclast turnover. Decreased bone turnover and stabilization of the bone matrix contribute to the analgesic effect of zoledronic acid with respect to painful osteoblastic lesions. The agent also reduces serum calcium concentrations associated with hypercalcemia.
A protein tyrosine kinase inhibitor that has specific activity for the epidermal growth factor receptor. (NCI)
A single-chain immunotoxin consisting of Fv fragments of the BR96 monoclonal antibody (MoAb) and a truncated Pseudomonas exotoxin (PE40) that lacking the binding domain. MoAb BR96 specifically binds to Lewis Y-related carbohydrate antigen, a cell surface antigen overexpressed in many carcinomas. After internalization, PE40 causes ADP-ribosylation of transcription elongation factor 2, thereby inactivating elongation factor 2 and inhibiting protein synthesis in the cancer cells.
An inherited or acquired peripheral neuropathy affecting the autonomic nervous system. It results in disruption of the involuntary body functions. Inherited causes include Fabry disease and porphyrias. Acquired causes include diabetes, uremia, hepatic disorders, vitamin deficiencies, toxins, and drug toxicities.
Vitamins that are freely soluble in water.
An electrocardiographic finding of partially blocked cardiac electrical impulse conduction along the fibers of one or both bundle branches.
Splitting of the sutured margins of a surgical wound. Risk factors include diabetes mellitus, obesity, and advanced age.
The most common type of cutaneous cyst. It results from the proliferation of epidermal cells in a circumscribed space within the dermis. It is usually asymptomatic and presents as a firm, round nodule.
Steatocystoma multiplex is a skin disorder characterized by the development of multiple noncancerous (benign) cysts known as steatocystomas. These growths begin in the skin's sebaceous glands, which normally produce an oily substance called sebum that lubricates the skin and hair. Steatocystomas are filled with sebum.In affected individuals, steatocystomas typically first appear during adolescence and are found most often on the torso, neck, upper arms, and upper legs. These cysts are usually the only sign of the condition. However, some affected individuals also have mild abnormalities involving the teeth or the fingernails and toenails.
A non-neoplastic lesion of the ureter characterized by the presence of multiple submucosal small cysts in the ureteral wall. It is caused by inflammation due to urinary tract stones or infection.
A genetic, non-inheritable disorder caused by osteoblastic differentiation defects that result in the replacement of bone marrow and trabecular bone by fibrous stroma and immature bone. It usually affects a single bone and less frequently multiple bones. Skull, femur, tibia, and humerus are the most frequently affected bones. It manifests with pain, deformities, and fractures.
A nevus composed of neoplastic melanocytes that infiltrate both the epidermis and the dermis.
An osteosarcoma usually arising from the metaphysis of long bones. It is characterized by the presence of a cystic architecture with blood-filled spaces. The prognosis is similar to that of conventional osteosarcoma.
A tumor composed of two or more glial cell types (astrocytes, ependymal cells, and oligodendrocytes).
A WHO grade III meningioma characterized by the presence of malignant morphologic features, including malignant cytology and a very high mitotic index (20 or more mitoses per ten high power fields).
A WHO grade III meningioma characterized by the predominant presence of rhabdoid cells forming sheets.
A nevus characterized by the presence of large epithelioid melanocytes.
Legal or illegal drugs created using SYNTHETIC CHEMISTRY TECHNIQUES.
A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.
A physiochemical process which occurs in a wide range of organisms which unlike BASAL METABOLISM is not required for or essential to short-term survivability but to long-term general well-being of the organism.
A record of a patient's medical background regarding the cancer and cancer-related problems of blood relatives.
A disorder characterized by the partial or complete loss of the ability to detect sounds due to damage to the ear structures or inability of the brain to properly interpret or process the auditory signals it receives from the anatomic structures of the ear.
A radiologic finding indicating the presence of abnormalities in the breast parenchyma identified in a mammogram performed for screening or diagnostic purposes. These abnormalities include calcifications, breast tissue distortion, presence of areas of density, and presence of benign or malignant tumors.
An electrocardiographic finding of a sinus beat followed by a premature atrial complexes for three or more consecutive cycles; a regularly irregular rhythm of normal and abnormal P waves in a 1-1 ratio. (CDISC)
Blood pressure in the zone between the highest normal level and the level that is considered hypertensive.
A carcinoma arising from the ampulla of Vater. The vast majority of cases are adenocarcinomas. Signs and symptoms include jaundice, abdominal pain, anorexia, nausea, vomiting, and weight loss.
Degeneration of the cerebellum. It may be an inherited condition, a paraneoplastic syndrome, or secondary to autoimmune disorders.
X-linked cardiac valvular dysplasia is a rare X-linked form of heart disease characterized by mitral and/or aortic valve regurgitation. Only males have been diagnosed as affected, while carrier females are asymptomatic. The histologic features do not differ from the common severe and idiopathic mitral valve prolapse.
A uniocular condition in which there is fixation of an object by a point other than the fovea. This point adopts the principal visual direction. The degree of the eccentric fixation is defined by its distance from the fovea in degrees.
Excessive wrinkling of the skin of the face.
A polypoid tumor that arises from the gallbladder and projects into the lumen. This category includes adenomas and hyperplastic polyps.
A molecular or cytogenic abnormality which occurs in either human disease states or disease models.
Phenomenon where BLOOD PRESSURE readings are elevated only when taken in clinical settings.
A condition in which the anterior part of the foot rotates outward away from the midline of the body and the heel remains straight.
Paralysis that is caused by damage to a nerve.
A neuroendocrine carcinoma composed of small malignant cells which are often said to resemble ""oat cells"" under the microscope. Small cell carcinoma most often affects the lungs. Clinically, this is often a rapidly growing cancer that spreads to distant sites early.
A benign tumor arising from the parenchymal cells of the parathyroid glands. In the vast majority of cases, the tumor involves a single parathyroid gland. It is associated with the symptoms of primary hyperparathyroidism, resulting from the excessive production of parathyroid hormone. It is usually surrounded by a well-defined capsule. Capsular invasion, vascular invasion, and perineural invasion are absent.
Reduced attention span characterized by distractibility and impulsivity but not necessarily satisfying the diagnostic criteria for attention deficit hyperactivity disorder.
An abnormality of the sweat gland. [HPO:probinson]
Abnormality of the thymus, an organ located in the upper anterior portion of the chest cavity just behind the sternum and whose main function is to provide an environment for T lymphocyte maturation.
Repeated infections of the urinary tract.
A carcinoma arising from the vaginal epithelium. The majority of vaginal carcinomas are squamous cell carcinomas.
A slight or incomplete paralysis of an extraocular muscle.
A record of a patient's background regarding health and the occurrence of disease events of the individual. In addition, personal medical history may be a variable in epidemiologic studies.
A germ cell tumor arising in an anatomic site other than the testis or ovary (e.g., central nervous system, lung, mediastinum, and retroperitoneum).
A derivative of streptomycin, aminoglycoside antibiotic, with bactericidal property. Dihydrostreptomycin depends on active transport across the bacterial cell membrane before irreversibly binding S12 protein of the bacterial 30S ribosomal subunit. As a result, this agent interferes with the initiation complex between messenger RNA and the bacterial ribosome thereby causing the misreading of the genetic code resulting in the production of non-functional proteins, consequently leading to bacterial cell death.
A chronic inflammatory skin condition characterized by itchiness and a rash in the chest and abdominal areas. It affects males more than females and is usually contracted at a relatively young age. It is thought to be caused by an allergic reaction to food, insect bites, or medication.
A chronic, sporadic, acquired pruritic non-infectious skin condition characterized by one or more well defined inflamed (pink or red) patches or plaques of varying size.
Inflammation of the blood vessel wall characterized by palpable purpura.
Inflammation surrounding hair follicles.
A collection of pus that has formed in the axilla.
Dermatitis caused by an allergic reaction to arnica.
Contact dermatitis caused by exposure to alkalis.
Allergic contact dermatitis caused by exposure to dichromate.
Inflammation of the skin resulting from exposure to the sun.
A benign, self-limited eruption of vesicles, pustules, papules and macules seen in newborns. An eosinophilic infiltrate can be isolated suggesting an immune-mediated reaction in the skin.
A form of physical urticaria, in which contact with water, regardless of its temperature and source, evokes pruritic follicular wheals on the skin. [PMID:22346281]
A rare condition that stimulated chronic radiodermatitis. It is considered a variant of mycosis fungoides.
A variant of parapsoriasis in which the plaques are small.
Confluent and reticulated papillomatosis is a dermatologic disorder characterized by onset in the teenage or young adult years of hyperkeratotic 1- to 2-mm papules that increase in size to 4 to 5 mm and coalesce to form a reticular pattern peripherally and a confluent pattern centrally. Early papules can be erythematous and later turn brown. Affected individuals are usually otherwise asymptomatic. The condition is distinct from acanthosis nigricans and tinea versicolor (infection with the yeast Pityrosporum), but can appear similar. Microscopic examination of skin biopsy shows epidermal undulation with hyperkeratosis, squat papillomatosis, and occasional acanthotic downward projections from the bases of the dells between papillomatous areas. Antibacterial agents such as minocycline and azithromycin are effective, perhaps due to their antiinflammatory and immunomodulatory properties (summary by Scheinfeld, 2006).
A non-hereditary form of ichthyosis characterized by plate-like scales on the legs, arms and occasionally the torso.
A connective tissue disorder characterized by widespread thickening of SKIN with a cobblestone-like appearance. It is caused by proliferation of FIBROBLASTS and deposition of MUCIN in the DERMIS in the absence of thyroid disease. Most scleromyxedema cases are associated with a MONOCLONAL GAMMOPATHY, immunoglobulin IgG-lambda.
A pink-blue mottled or marbled appearance of the skin secondary to exposure to cold temperatures, which is generally alleviated by rewarming.
A type of localized scleroderma characterized by a long strip of indurated skin, which is typically found unilaterally on an arm or leg, and sometimes on the forehead or trunk. This disorder often affects the tissues beneath the skin, causing damage to bones, muscle or other organs. It can limit movement, alter growth, and disfigure the affected area.
The presence of convoluted folds and furrows formed from thickened skin of the scalp, resembling cerebriform pattern. The scalp has convoluted and elevated folds, 1 to 2 cm in thickness. The convolutions generally cannot be flattened by traction.
Hyperkeratosis lenticularis perstans (HLP) is a rare cutaneous disorder occurring in older persons and manifested by multiple benign pink to reddish-brown keratotic papules that primarily affect the extremities. The disorder was first described by Flegel (1958) (summary by Bean, 1972).
Symmetrical vermiform facial atrophy that affects mainly the forehead, the chin, the ear lobes and helices. Atrophodermia vermiculata is characterized by erythema and follicular plugs on the cheeks, developing into painless reticular impressions.
Atrophoderma vermiculata, a form of keratosis pilaris atrophicans, typically presents in childhood with erythema and follicular keratotic papules that slowly progress to characteristic atrophy, which has been described as worm-eaten, reticular, or honeycomb, and occurs on the cheeks, preauricular area, and forehead. More rarely, the atrophy may extend to the upper lip, helices, ear lobes, and, in some cases, the limbs. The degree of inflammation, the presence of milia, and the extent of follicular plugs are variable (summary by Luria and Conologue, 2009).
Severe and chronic form of acne characterized by large, burrowing abscesses associated with disfigurement.
A papular eruption of unknown etiology that progresses to residual papular erythema and scaling usually confined to the area of the mouth, and almost exclusively occurring in young women. It may also be localized or extend to involve the eyelids and adjacent glabella area of the forehead (periocular dermatitis). (Dorland, 28th ed)
ACNE-like skin eruptions caused by exposure to CHLORINE-containing compounds. Exposure can be by inhalation, ingestion, or through the skin. Chloracne is often seen in people who have occupational contact with chlorinated pesticides, wood preservatives, and sealants.
A perceived unpleasant smell given off by the body.
Trichorrhexis nodosa is the formation of nodes along the hair shaft through which breakage readily occurs. It is thus a focal defect in the hair fiber that is characterized by thickening or weak points (nodes) that cause the hair to break off easily. The result is defective, abnormally fragile hair.
Pili annulati, or 'ringed hair,' is a disorder in which scalp hairs show alternating light and dark bands. It is often an incidental finding, and the hair usually does not show increased fragility (Green et al., 2004). See also pseudopili annulati (613241), a distinct entity.
Fragile, easily breakable hair, i.e., with reduced tensile strength.
Pili (from Latin pilus, hair) torti (from Latin tortus, twisted) refers to short and brittle hairs that appear flattened and twisted when viewed through a microscope.
Development of gray hair at a younger than normal age.
Perifolliculitis capitis abscedens et suffodiens is a chronic inflammatory disease of the scalp characterized by the presence of large and small nodules that suppurate and intercommunicate by sinus formation. It may be more frequent in black males than in others (summary by McMullan and Zeligman, 1956).
A scalp hair loss condition characterized by excessive shedding of hair in the resting phase of growth, usually following a fever or major body stress.
An abnormal loss of anagen (growth phase) hairs.
A nail that is diminished in length and width, i.e., underdeveloped nail.
The presense of a depressed line (""canal"") in the center of the nail.
A nail plate that has a longitudinal separation and the two sections of the nail share the same lateral radius of curvature.
Linear transverse/horizontal groove of one or more nail plates that migrate distally from the proximal nail fold with nail growth, usually secondary to illness, trauma or malnutrition.
Nail that appears thick when viewed on end.
Complete shedding (separation) of the nail from the proximal matrix. Onychomadesis is the proximal separation of the nail plate from the nail matrix due to a temporary cessation of nail growth.
A benign lesion that is sometimes congenital and consists of an overgrowth of the epidermis and the presence of melanin-containing cells. It is found mostly in males and typically develops during childhood or adolescence, becoming darker and more hairy after puberty.
An autoimmune disorder, similar to systemic lupus erythematosus, that is caused by certain drugs.
Urticaria in response to exposure to ultraviolet-A (UVA), ultraviolet-B (UVB), visible and rarely infrared light. [PMID:29315482]
Deposition of calcium salts in subcutaneous tissue (i.e., the the lowermost layer of the integument).
An extremely rare benign condition characterized by large calcified periarticular soft tissue masses composed of calcium salts, usually located around large joints. Tumoral calcinosis can occur due to HYPERPHOSPHATEMIA in patients with UREMIA and/or who are undergoing RENAL DIALYSIS.
Angioma serpiginosum (AS) is a rare benign congenital skin disorder characterized by nonpurpuric red punctate lesions seen histologically as capillary ectasias in the superficial papillary dermis. The lesions often follow Blaschko lines and are most commonly found in females (90%) (Blinkenberg et al., 2007). See 106050 for additional phenotypic information and possible autosomal dominant inheritance or cutaneous somatic mosaicism (Chen et al., 2006; Blinkenberg et al., 2007).
An angiokeratoma that is located on the scrotum.
Flesh-colored or yellowish papules, 2 mm or larger, that are responses to internal mechanical pressure and weakness in the connective tissue in the dermis, appear commonly over the medial aspect of the heel, but in some cases on the wrists. They are thought to represent herniations of adipose tissue through the plantar fascia retinaculum.
disorders of the skeletal system; includes both bone and cartilage.
A type of morphea characterized by four or more plaques found in two or more anatomic locations. The plaques are indurated, generally well-delineated, and may include muscle atrophy in affected areas; there is no visceral involvement.
An inflammatory myopathy of childhood resulting in muscle weakness, and associated with a characteristic skin rash.
A form of arthritis that affects hemophiliacs, which is characterized by bleeding into the joint space.
Bony swelling of the proximal interphalangeal joint (PIP) associated with the formation of osteophytes (calcific spurs) of the articular (joint) cartilage thzat are visible radiographically.
Shoulder dislocation occurring repeated times. [PMID:29197942, Sanford:krageth]
Degenerative arthritis of the spinal column.
A chronic inflammatory disorder characterized by hyperostosis, osteitis, synovitis and palmoplantar pustulosis. The most common site of involvement is the anterior chest wall.
Decreased height of the intervertebral disk.
Any degenerative disorder affecting one or more vertebral discs of the thoracic spine.
Any degenerative disorder affecting one or more vertebral discs of the lumbar spine.
Disorder of back including back of neck.
Partial dislocation of the atlantoaxial joint.
Inflammation or irritation of a JOINT CAPSULE.
Rupture of the tendons in the ROTATOR CUFF of the shoulder joint due to injury.
Horn-like malformations of the iliac crests with symmetrical bilateral central posterior iliac processes. A characteristic finding in the Nail-Patella syndrome. Iliac horns are visible on X-ray and may be palpable, but are asymptomatic.
A non-neoplastic or neoplastic disorder that affects the soft tissue.
Benign skin fibromas, typically occurring over the small joints of the hands and feet, that are associated with repetitive friction or pressure.
Inflammation and induration of the fascia related to an accumulation of white blood cells, including eosinophils.
The finding of one or more vertebral compression (crush) fractures in the absence of local disease or high-energy trauma or the presence of both a clinically significant fracture history and BMD Z-score less than or equal to -2.0. A clinically significant fracture history is one or more of the following: 1) two or more long bone fractures by age ten years; 2) three or more long bone fractures at any age up to age nineteen years. (from 2013 International Society for Clinical Densitometry definition of Osteoporosis-Pediatric)
Thiemann disease is a rare disorder that is considered to be a form of avascular necrosis of the proximal interphalangeal joints of the fingers and toes. The clinical symptoms usually appear in adolescence (Kotevoglu-Senerdem et al., 2003).
Inflammation of a bony outgrowth located near the attachment site for muscles.
A condition caused by degenerative arthritis (see OSTEOARTHRITIS) of the METATARSOPHALANGEAL JOINT of the great toe and characterized by pain and limited dorsiflexion, but relatively unrestricted plantar flexion.
For children from birth to 4 years of age the palm width is more than 2 SD above the mean; for children from 4 to 16 years of age the palm width is above the 95th centile; or, the width of the palm appears disproportionately wide for the length.
An abnormal forward-flexed posture e.g. forward flexion of the spine, which is noticeable when standing or walking but disappears when lying down. It is becoming an increasingly recognized feature of Parkinson's disease and dystonic disorders.
Nasal ridge curving posteriorly to an imaginary line that connects the nasal root and tip.
A rounded, bulging chest that resembles the shape of a barrel. That is, there is an increased anteroposterior diameter and usually some degree of kyphosis.
Impaired or altered function of related components of the somatic (body framework) system: skeletal, arthrodial and myofascial structures, and their related vascular, lymphatic and neural elements. Somatic dysfunction is treatable using osteopathic manipulative treatment. The positional and motion aspects of somatic dysfunction are best described using at least one of three parameters: 1). The position of a body part as determined by palpation and referenced to its adjacent defined structure, 2). The directions in which motion is freer, and 3). The directions in which motion is restricted.
A polyp that arises from the paranasal sinus mucosa. Causes include allergic rhinitis, chronic sinusitis, and cystic fibrosis. It is characterized by the presence of edematous tissue infiltrated by inflammatory cells, including eosinophils.
Epithelium-lined, mucus-containing cystic masses filling one or more of the paranasal sinuses.
A polyp that arises from the maxillary sinus mucosa. It is characterized by the presence of edematous tissue infiltrated by inflammatory cells, including eosinophils. Causes include allergic rhinitis, chronic sinusitis, and cystic fibrosis.
A polyp that arises from the ethmoid sinus mucosa. It is characterized by the presence of edematous tissue infiltrated by inflammatory cells, including eosinophils. Causes include allergic rhinitis, chronic sinusitis, and cystic fibrosis.
A polyp that arises from the sphenoid sinus mucosa. It is characterized by the presence of edematous tissue infiltrated by inflammatory cells, including eosinophils. Causes include allergic rhinitis, chronic sinusitis, and cystic fibrosis.
A cervical cyst that occurs as a result of the persistence of one or more of the pharyngeal grooves.
A congenital or acquired condition of underdeveloped or degeneration of CARTILAGE in the LARYNX. This results in a floppy laryngeal wall making patency difficult to maintain.
Blockage of the laryngeal airway passage.
A clinical term that indicates the presence of a white patch on the mucosal surface of the vocal cords. In most cases histologic examination reveals keratosis.
Abnormal deposits of calcium in the tracheal tissue.
A congenital or acquired abnormality of the wall of the bronchi. In congenital cases, there is lack of rigidity in the cartilage of the bronchial wall. In acquired cases, the cartilage of the bronchial wall is degenerated, secondary to tracheostomy or presence of a breathing tube. Symptoms include noisy breathing and wheezing.
A pneumothorax condition marked by complete absence of markings in the chest radiograph.
Asthma is a chronic disease that affects your airways. Your airways are tubes that carry air in and out of your lungs. If you have asthma, the inside walls of your airways become sore and swollen. In the United States, about 20 million people have asthma. Nearly 9 million of them are children. Children have smaller airways than adults, which makes asthma especially serious for them. Children with asthma may experience wheezing, coughing, chest tightness, and trouble breathing, especially early in the morning or at night. . Many things can cause asthma, including. - Allergens - mold, pollen, animals. -Irritants - cigarette smoke, air pollution. -Weather - cold air, changes in weather. -Exercise . -Infections - flu, common cold. When asthma symptoms become worse than usual, it is called an asthma attack. Asthma is treated with two kinds of medicines: quick-relief medicines to stop asthma symptoms and long-term control medicines to prevent symptoms. .
Asthma attacks caused, triggered, or exacerbated by OCCUPATIONAL EXPOSURE.
Pneumoconiosis caused by inhalation of kaolin dust.
Life-threatening respiratory failure that develops rapidly. Causes include injury, sepsis, drug overdose, and pancreatitis. It manifests with dyspnea and cyanosis and may lead to cardiovascular shock.
A lymphocyte-predominant infiltration of the lungs characterized by bibasilar pulmonary infiltrates with dense interstitial accumulations of lymphocytes and plasma cells.
Severe complication of pneumonia characterized by liquefaction of lung tissue.
Displacement of structures in the thoracic cavity in one direction due to increased pleural pressure on the contralateral side.
A type of apraxia that is characterized by difficulty or inability to execute speech movements because of problems with coordination and motor problems, leading to incorrect articulation. An increase of errors with increasing word and phrase length may occur. [HPO:probinson]
A condition of high blood pressure occurring in association with diseases of the endocrine glands.
A rare movement disorder developed during PREGNANCY, characterized by involuntary jerky motion (CHOREA) and inability to maintain stable position of body parts (ATHETOSIS). RHEUMATIC FEVER and collagen vascular disorders are frequently associated with this disease. Chorea may vary from mild to severe and occurs in approximately 1 per 2,000 to 3,000 pregnancies. (From Md Med J 1997 Sep;46(8):436-9)
A disorder characterised by persistent eosinophilia and acute endocardial lesions, which may progress to endomyocardial fibrosis; most cases are idopathic, but there is some association with malignant tumors.
An often fatal inflammatory disorder that affects the myocardium. Morphologically, it is characterized by the presence of an inflammatory infiltrate in the myocardial tissue that includes multinucleated giant cells. It is often associated with the presence of an autoimmune disorder. Patients present with arrhythmias and/or heart failure. Heart transplantation is the only treatment option available.
Dysfunction of one of the cardiac valves characterized by incomplete valve closure.
A heart disorder characterized by a defect in tricuspid valve structure or function.
Myxomatous mitral valve is defined as the presence of excess leaflet tissue and leaflet thickening greater than 5 mm, resulting in a prolapse greater than 2 mm into the left atrium on parasternal long axis view.
A disorder affecting the conduction system that sends electrical signals in the myocardium.
An electrocardiographic finding of an arrhythmia originating from within the atrioventricular node.
Extra impulse-conducting tissue in the heart that creates abnormal impulse-conducting connections between HEART ATRIA and HEART VENTRICLES.
An electrocardiographic finding of premature ventricular complexes which have a single distinct morphology, suggesting origin at one ventricular site.
An intermittent atrioventricular block with failure of some atrial impulses to conduct to the ventricles, i.e., some but not all atrial impulses are conducted through the atrioventricular node and trigger ventricular contraction.
A disorder characterized by an electrocardiographic finding of intermittent failure of atrial electrical impulse conduction to the ventricles, characterized by a progressively lengthening PR interval prior to the block of an atrial impulse. (CDISC)
Conduction block in the anterior division of the left bundle branch of the bundle of His.
Conduction block in the posterior division of the left bundle branch of the bundle of His.
An electrocardiographic finding comprising right bundle branch block and left anterior fascicular block, or right bundle branch block and left posterior fascicular block. Defects occurring in two of the three divisions of the conduction system of the heart are considered bifascicular blocks. Technically left bundle branch block may be considered a bifascicular block.
A heterogeneous group of diseases characterized by inflammation and necrosis of the blood vessel walls.
Abnormal outpouching or sac-like dilatation in the wall of the celiac artery.
Abnormal outpouching or sac-like dilatation in the wall of the superior mesenteric artery .
Blockage of blood flow through an artery.
A ruptured aneurysm located in the wall of the proximal portion of the descending aorta proceeding from the arch of the aorta.
A ruptured aneurysm located in the portion of the descending aortic wall that is within the abdomen.
A abnormal, congenital formation or mark on the skin or neighboring mucosa that does not show neoplastic growth.
A hemorrhoid which originates above the dentate line.
A hemorrhoid which originates below the dentate line.
Complete obstruction of a carotid artery.
The pericardium is a membrane, or sac, that surrounds your heart. It holds the heart in place and helps it work properly. Problems with the pericardium include. -Pericarditis - an inflammation of the sac. It can be from a virus or other infection, a heart attack, heart surgery, other medical conditions, injuries, and certain medicines. -Pericardial effusion - the buildup of fluid in the sac. -Cardiac tamponade - a serious problem in which buildup of fluid in the sac causes problems with the function of the heart. Symptoms of pericardial problems include chest pain, rapid heartbeat, and difficulty breathing. Fever is a common symptom of acute pericarditis. Your doctor may use a physical exam, imaging tests, and heart tests to make a diagnosis. Treatment depends on the cause. NIH: National Heart, Lung, and Blood Institute.
Inflammation of the pericardium associated with chronic kidney failure.
A condition that is caused by trauma to the lymph system, which disrupts the normal flow of lymph fluid. This is most often due to surgery that requires lymph node removal or a large amount of lymph tissue. This disruption is especially apparent if the lymph nodes under the arm and arm and around the breast are compromised due to breast cancer surgery, diagnostic dissection, mastectomy, or radiation.
A rare autosomal recessive inherited syndrome. It is characterized by xeroderma pigmentosum, mental retardation, dwarfism, hypogonadism, and neurologic abnormalities.
A rare autosomal recessive inherited syndrome caused by mutations in the ATR gene, RBBP8 gene, CENPJ gene, CEP152 gene, CEP63 gene, NIN gene, DNA2 gene, or TRAIP gene. It is characterized by intrauterine growth retardation, dwarfism, microcephaly, mental retardation, and a ""bird-headed"" facial appearance.
A rare autosomal recessive or dominant inherited disorder. The autosomal recessive form is caused by mutations in the ROR2 gene. There is no causative mutation identified for the autosomal dominant form. It is manifested with short limbs, abnormal facial features, underdeveloped genitalia, and wedge-shaped vertebrae.
EZH2-related overgrowth includes EZH2-related Weaver syndrome at one end of the spectrum and tall stature at the other. Although most individuals diagnosed with a heterozygous EZH2 pathogenic variant have been identified because of a clinical suspicion of Weaver syndrome, a minority have been identified through molecular genetic testing of family members of probands or individuals with overgrowth who did not have a clinical diagnosis of Weaver syndrome. Thus, the extent of the phenotypic spectrum associated with a heterozygous EZH2 pathogenic variant is not yet known. Weaver syndrome is characterized by tall stature, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft doughy skin, camptodactyly of the fingers and/or toes, umbilical hernia, abnormal tone, and hoarse low cry in infancy. Brain MRI has identified abnormalities in a few individuals with EZH2-related overgrowth. Neuroblastoma occurs at a slightly increased frequency in individuals with a heterozygous EZH2 pathogenic variant but data are insufficient to determine absolute risk. There is currently no evidence that additional malignancies (including hematologic malignancies) occur with increased frequency.
The Marshall-Smith syndrome is a malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia (Adam et al., 2005).
A form of arthrogryposis primarily affecting the hands and the feet.
A rare, lethal, autosomal recessive inherited syndrome characterized by pulmonary hypoplasia, central nervous system malformations, and hepatic malformations.
The phenotypic spectrum of L1 syndrome includes: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS); MASA syndrome (mental retardation [intellectual disability], aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs); SPG1 (X-linked complicated hereditary spastic paraplegia type 1); and X-linked complicated corpus callosum agenesis. Males with HSAS are born with severe hydrocephalus, adducted thumbs, and spasticity; intellectual disability is severe. In less severely affected males, hydrocephalus may be subclinically present and documented only because of developmental delay; intellectual disability ranges from mild (IQ: 50-70) to moderate (IQ: 30-50).
Neu-Laxova syndrome is an autosomal recessive lethal multiple malformation syndrome characterized by ichthyosis, marked intrauterine growth restriction, microcephaly, short neck, central nervous system anomalies (lissencephaly, cerebellar hypoplasia and/or abnormal/agenesis of the corpus callosum), limb deformities, hypoplastic lungs, edema, and abnormal facial features including severe proptosis with ectropion, hypertelorism, micrognathia, flattened nose, and malformed ears (summary by Manning et al., 2004). Genetic Heterogeneity of Neu-Laxova Syndrome NLS2 (616038) is caused by mutation in the PSAT1 gene (610936) on chromosome 9q21.
PAFAH1B1-associated lissencephaly includes Miller-Dieker syndrome (MDS), isolated lissencephaly sequence (ILS), and (rarely) subcortical band heterotopia (SBH). Lissencephaly and SBH are cortical malformations caused by deficient neuronal migration during embryogenesis. Lissencephaly refers to a ""smooth brain"" with absent gyri (agyria) or abnormally wide gyri (pachygyria). SBH refers to a band of heterotopic gray matter located just beneath the cortex and separated from it by a thin zone of normal white matter. MDS is characterized by lissencephaly, typical facial features, and severe neurologic abnormalities. ILS is characterized by lissencephaly and its direct sequelae: developmental delay, intellectual disability, and seizures.
Pallister-Hall syndrome (referred to as PHS in this entry) is characterized by a spectrum of anomalies ranging from polydactyly, asymptomatic bifid epiglottis, and hypothalamic hamartoma at the mild end to laryngotracheal cleft with neonatal lethality at the severe end. Individuals with mild PHS may be incorrectly diagnosed as having isolated postaxial polydactyly type A. Individuals with PHS can have pituitary insufficiency and may die as neonates from undiagnosed and untreated adrenal insufficiency.
Walker-Warburg syndrome is an inherited disorder that affects development of the muscles, brain, and eyes. It is the most severe of a group of genetic conditions known as congenital muscular dystrophies, which cause muscle weakness and wasting (atrophy) beginning very early in life. The signs and symptoms of Walker-Warburg syndrome are present at birth or in early infancy. Because of the severity of the problems caused by Walker-Warburg syndrome, most affected individuals do not survive past age 3.Walker-Warburg syndrome affects the skeletal muscles, which are muscles the body uses for movement. Affected babies have weak muscle tone (hypotonia) and are sometimes described as ""floppy."" The muscle weakness worsens over time.Walker-Warburg syndrome also affects the brain; individuals with this condition typically have a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead develops a bumpy, irregular appearance (like that of cobblestones). These individuals may also have a buildup of fluid in the brain (hydrocephalus) or abnormalities of certain parts of the brain, including a region called the cerebellum and the part of the brain that connects to the spinal cord (the brainstem). These changes in the structure of the brain lead to significantly delayed development and intellectual disability. Some individuals with Walker-Warburg syndrome experience seizures.Eye abnormalities are also characteristic of Walker-Warburg syndrome. These can include unusually small eyeballs (microphthalmia), enlarged eyeballs caused by increased pressure in the eyes (buphthalmos), clouding of the lenses of the eyes (cataracts), and problems with the nerve that relays visual information from the eyes to the brain (the optic nerve). These eye problems lead to vision impairment in affected individuals.
An association of DIABETES MELLITUS with Prader-Willi Syndrome.
Cohen syndrome is characterized by failure to thrive in infancy and childhood; truncal obesity in the teen years; early-onset hypotonia and developmental delays; microcephaly developing during the first year of life; moderate to profound psychomotor retardation; progressive retinochoroidal dystrophy and high myopia; neutropenia in many with recurrent infections and aphthous ulcers in some; a cheerful disposition; joint hypermobility; and characteristic facial features.
Freeman-Sheldon syndrome (FSS), or DA2A, is phenotypically similar to DA1. In addition to contractures of the hands and feet, FSS is characterized by oropharyngeal abnormalities, scoliosis, and a distinctive face that includes a very small oral orifice (often only a few millimeters in diameter at birth), puckered lips, and an H-shaped dimple of the chin; hence, FSS has been called 'whistling face syndrome.' The limb phenotypes of DA1 and FSS may be so similar that they can only be distinguished by the differences in facial morphology (summary by Bamshad et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Schinzel-Giedion syndrome is a highly recognizable syndrome characterized by severe mental retardation, distinctive facial features, and multiple congenital malformations including skeletal abnormalities, genitourinary and renal malformations, and cardiac defects, as well as a higher-than-normal prevalence of tumors, notably neuroepithelial neoplasia (summary by Hoischen et al., 2010).
An autosomal recessive inherited disorder. It is characterized by arthrogryposis, facial anomalies, polyhydramnios, camptodactyly, intrauterine growth retardation, and pulmonary hypoplasia. Pulmonary hypoplasia is present in the vast majority of cases and is often the fatal component of this syndrome.
A rare, autosomal recessive inherited disorder caused by mutations in the FRAS1, FREM2, or GRIP1 genes. It is characterized by the presence of cryptophthalmos, cutaneous syndactyly, and genitourinary abnormalities.
An autosomal dominant disorder manifested by various combinations of preauricular pits, branchial fistulae or cysts, lacrimal duct stenosis, hearing loss, structural defects of the outer, middle, or inner ear, and renal dysplasia. Associated defects include asthenic habitus, long narrow facies, constricted palate, deep overbite, and myopia. Hearing loss may be due to Mondini type cochlear defect and stapes fixation. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)
Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals.A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing.Many people with Stickler syndrome have severe nearsightedness (high myopia). In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases.In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear.Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain.Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals.A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder.
A congenital birth defect characterized by incomplete development or absence of face structures, usually affecting one side of the face. The defects include partially formed or absent ear, nose, lip, mandible, and/or soft palate.
Nager syndrome is the prototype for a group of disorders collectively referred to as the acrofacial dysostoses (AFDs), which are characterized by malformation of the craniofacial skeleton and the limbs. The major facial features of Nager syndrome include downslanted palpebral fissures, midface retrusion, and micrognathia, the latter of which often requires the placement of a tracheostomy in early childhood. Limb defects typically involve the anterior (radial) elements of the upper limbs and manifest as small or absent thumbs, triphalangeal thumbs, radial hypoplasia or aplasia, and radioulnar synostosis. Phocomelia of the upper limbs and, occasionally, lower-limb defects have also been reported. The presence of anterior upper-limb defects and the typical lack of lower-limb involvement distinguishes Nager syndrome from Miller syndrome (263750), another rare AFD; however, distinguishing Nager syndrome from other AFDs, including Miller syndrome, can be challenging (summary by Bernier et al., 2012).
Townes-Brocks syndrome is a genetic condition that affects several parts of the body. The most common features of this condition are an obstruction of the anal opening (imperforate anus), abnormally shaped ears, and hand malformations that most often affect the thumb. Most people with this condition have at least two of these three major features.Other possible signs and symptoms of Townes-Brocks syndrome include kidney abnormalities, mild to profound hearing loss, heart defects, and genital malformations. These features vary among affected individuals, even within the same family. Intellectual disability or learning problems have also been reported in about 10 percent of people with Townes-Brocks syndrome.
A dysmorphic syndrome characterized by short stature, microcephaly, mental deficiency, peculiar facies, hypoplastic genitalia, and skeletal anomalies.
Mild mental deficiency with growth retardation, ocular defects, and limb abnormalities.
Coffin-Lowry syndrome (CLS) is usually characterized by severe-to-profound intellectual disability in males; less severely impaired individuals have been reported. Neuropsychiatric concerns can include behavioral problems, loss of strength, progressive spasticity or paraplegia, sleep apnea, or stroke. Stimulus-induced drop attacks (SIDAs) in which unexpected tactile or auditory stimuli or excitement triggers a brief collapse but no loss of consciousness are present in approximately 20% of affected individuals. Typically SIDAs begin between mid-childhood and the teens. Characteristic facial features may be more apparent with age. Upper-extremity differences may be subtle and include short, soft, fleshy hands with tapered fingers as well as fleshy forearms. Progressive kyphoscoliosis is one of the most difficult aspects of long-term care. Affected females tend to have intellectual disability in the mild to moderate range and may also have the typical facial, hand, and skeletal findings noted in males.
Stickler syndrome is a connective tissue disorder that can include ocular findings of myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate (either alone or as part of the Robin sequence); and mild spondyloepiphyseal dysplasia and/or precocious arthritis. Variable phenotypic expression of Stickler syndrome occurs both within and among families; interfamilial variability is in part explained by locus and allelic heterogeneity.
Miller syndrome, or postaxial acrofacial dysostosis, is a rare autosomal recessive disorder characterized clinically by severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the postaxial elements of the limbs, coloboma of the eyelids, and supernumerary nipples (summary by Ng et al., 2010).
IRF6-related disorders span a spectrum from isolated cleft lip and palate and Van der Woude syndrome (VWS) at the mild end to popliteal pterygium syndrome (PPS) at the more severe end. Individuals with VWS show one or more of the following anomalies: Congenital, usually bilateral, paramedian lower-lip fistulae (pits) or sometimes small mounds with a sinus tract leading from a mucous gland of the lip. Cleft lip (CL). Cleft palate (CP). Note: Cleft lip with or without cleft palate (CL±P) is observed about twice as often as CP only. Submucous cleft palate (SMCP). The PPS phenotype includes the following: CL±P. Fistulae of the lower lip. Webbing of the skin extending from the ischial tuberosities to the heels. In males: bifid scrotum and cryptorchidism. In females: hypoplasia of the labia majora. Syndactyly of fingers and/or toes. Anomalies of the skin around the nails. A characteristic pyramidal fold of skin overlying the nail of the hallux (almost pathognomonic). In some non-classic forms of PPS: filiform synechiae connecting the upper and lower jaws (syngnathia) or the upper and lower eyelids (ankyloblepharon). In both VWS and PPS, growth and intelligence are normal.
Grebe chondrodysplasia is an autosomal recessive disorder characterized by severe abnormality of the limbs and limb joints. The severity of limb shortening progresses in a proximal-distal gradient, with the hands and feet being most affected. The fingers and toes lack articulation and appear as skin appendages. In contrast, axial skeletal structures and the craniofacial skeleton are not affected. Heterozygous individuals are of average stature and have mild skeletal abnormalities (summary by Thomas et al., 1997).
Multiple pterygium syndromes comprise a group of multiple congenital anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis) (Morgan et al., 2006). The multiple pterygium syndromes are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal (253290) and nonlethal (Escobar) types.
Femoral-facial syndrome (FFS), also known as femoral hypoplasia-unusual facies syndrome (FHUFS), is a rare and sporadic multiple congenital anomaly syndrome comprising bilateral femoral hypoplasia and characteristic facial features, such as long philtrum, thin upper lip, micrognathia with or without cleft palate, upward-slanting palpebral fissures, and a short nose with broad tip. Other features, such as renal anomalies, are more variable (summary by Nowaczyk et al., 2010).
Holt-Oram syndrome (HOS) is characterized by: Upper-extremity malformations involving radial, thenar, or carpal bones; and Variably, one or both of the following: Personal and/or family history of congenital heart malformation, most commonly ostium secundum atrial septal defect (ASD) and ventricular septal defect (VSD), especially those occurring in the muscular trabeculated septum. Cardiac conduction disease. An abnormal carpal bone is present in all affected individuals and may be the only evidence of disease. Seventy-five percent of individuals with HOS have a congenital heart malformation.
The NSDHL-related disorders include: CHILD (congenital hemidysplasia with ichthyosiform nevus and limb defects) syndrome, an X-linked condition that is usually male lethal during gestation and thus predominantly affects females; and CK syndrome, an X-linked disorder that affects males. CHILD syndrome is characterized by unilateral distribution of ichthyosiform (yellow scaly) skin lesions and ipsilateral limb defects that range from shortening of the metacarpals and phalanges to absence of the entire limb. Intellect is usually normal. The ichthyosiform skin lesions are usually present at birth or in the first weeks of life; new lesions can develop in later life. Nail changes are also common. The heart, lung, and kidneys can also be involved. CK syndrome (named for the initials of the original proband) is characterized by mild to severe cognitive impairment and behavior problems (aggression, attention deficit hyperactivity disorder, and irritability). All affected males reported have developed seizures in infancy and have cerebral cortical malformations and microcephaly. All have distinctive facial features, a thin habitus, and relatively long, thin fingers and toes. Some have scoliosis and kyphosis. Strabismus is common. Optic atrophy is also reported.
Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.
Lacrimoauriculodentodigital syndrome is a multiple congenital anomaly disorder mainly affecting lacrimal glands and ducts, salivary glands and ducts, ears, teeth, and distal limb segments (summary by Rohmann et al., 2006).
The term achondrogenesis has been used to characterize the most severe forms of chondrodysplasia in humans, invariably lethal before or shortly after birth. Achondrogenesis type I is a severe chondrodystrophy characterized radiographically by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death (Maroteaux and Lamy, 1968; Langer et al., 1969). In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues. Classification of Achondrogenesis Achondrogenesis was traditionally divided into 2 types: type I (Parenti-Fraccaro) and type II (Langer-Saldino). Borochowitz et al. (1988) suggested that achondrogenesis type I of Parenti-Fraccaro should be classified into 2 distinct disorders: type IA, corresponding to the cases originally published by Houston et al. (1972) and Harris et al. (1972), and type IB (600972), corresponding to the case originally published by Fraccaro (1952). Analysis of the case reported by Parenti (1936) by Borochowitz et al. (1988) suggested the diagnosis of achondrogenesis type II, i.e., the Langer-Saldino type (200610). Type IA would be classified as lethal achondrogenesis, Houston-Harris type; type IB, lethal achondrogenesis, Fraccaro type; and type II, lethal achondrogenesis-hypochondrogenesis, Langer-Saldino type. Superti-Furga (1996) suggested that hypochondrogenesis should be considered separately from achondrogenesis type II because the phenotype can be much milder. Genetic Heterogeneity of Achondrogenesis Achondrogenesis type IB (ACG1B; 600972) is caused by mutation in the DTDST gene (606718), and achondrogenesis type II (ACG2; 200610) is caused by mutation in the COL2A1 gene (120140).
Clinical features of achondrogenesis type 1B (ACG1B) include extremely short limbs with short fingers and toes, hypoplasia of the thorax, protuberant abdomen, and hydropic fetal appearance caused by the abundance of soft tissue relative to the short skeleton. The face is flat, the neck is short, and the soft tissue of the neck may be thickened. Death occurs prenatally or shortly after birth.
Asphyxiating thoracic dystrophy, also known as Jeune syndrome, is an inherited disorder of bone growth characterized by a narrow chest, short ribs, shortened bones in the arms and legs, short stature, and extra fingers and toes (polydactyly). Additional skeletal abnormalities can include unusually shaped collarbones (clavicles) and pelvic bones, and and cone-shaped ends of the long bones in the arms and legs. Many infants with this condition are born with an extremely narrow, bell-shaped chest that can restrict the growth and expansion of the lungs. Life-threatening problems with breathing result, and people with asphyxiating thoracic dystrophy may live only into infancy or early childhood. However, in people who survive beyond the first few years, the narrow chest and related breathing problems can improve with age.Some people with asphyxiating thoracic dystrophy are born with less severe skeletal abnormalities and have only mild breathing difficulties, such as rapid breathing or shortness of breath. These individuals may live into adolescence or adulthood. After infancy, people with this condition may develop life-threatening kidney (renal) abnormalities that cause the kidneys to malfunction or fail. Heart defects and a narrowing of the airway (subglottic stenosis) are also possible. Other, less common features of asphyxiating thoracic dystrophy include liver disease, fluid-filled sacs (cysts) in the pancreas, dental abnormalities, and an eye disease called retinal dystrophy that can lead to vision loss.
Kniest dysplasia is a disorder of bone growth characterized by short stature (dwarfism) with other skeletal abnormalities and problems with vision and hearing.People with Kniest dysplasia are born with a short trunk and shortened arms and legs. Adult height ranges from 42 inches to 58 inches. Affected individuals have abnormally large joints that can cause pain and restrict movement, limiting physical activity. These joint problems can also lead to arthritis. Other skeletal features may include a rounded upper back that also curves to the side (kyphoscoliosis), severely flattened bones of the spine (platyspondyly), dumbbell-shaped bones in the arms and legs, long and knobby fingers, and an inward- and upward-turning foot (clubfoot).Individuals with Kniest dysplasia have a round, flat face with bulging and wide-set eyes. Some affected infants are born with an opening in the roof of the mouth called a cleft palate. Infants may also have breathing problems due to weakness of the windpipe. Severe nearsightedness (myopia) and other eye problems are common in Kniest dysplasia. Some eye problems, such as tearing of the back lining of the eye (retinal detachment), can lead to blindness. Hearing loss resulting from recurrent ear infections is also possible.
The TRPV4-associated disorders (previously considered to be clinically distinct phenotypes before their molecular basis was discovered) are now grouped into neuromuscular disorders and skeletal dysplasias; however, the overlap within and between both groups is considerable. Bilateral progressive sensorineural hearing loss (SNHL) can occur in both. The three neuromuscular disorders (mildest to most severe): Charcot-Marie-Tooth disease type 2C (CMT2C). Scapuloperoneal spinal muscular atrophy (SPSMA). Congenital distal spinal muscular atrophy (CDSMA). The neuromuscular disorders are characterized by a progressive peripheral neuropathy with variable combinations of laryngeal dysfunction (i.e., vocal fold paresis), respiratory dysfunction, and joint contractures. The six skeletal dysplasias: Mildest: Familial digital arthropathy-brachydactyly. Intermediate: Autosomal dominant brachyolmia. Spondylometaphyseal dysplasia, Kozlowski type. Spondyloepiphyseal dysplasia, Maroteaux type. Most severe: Parastremmatic dysplasia. Metatropic dysplasia. The skeletal dysplasia is characterized by brachydactyly (in all 6); the five that are more severe have short stature that varies from mild to severe with progressive spinal deformity and involvement of the long bones and pelvis. In the mildest of the TRPV4-associated disorders life span is normal; in the most severe it is shortened.
The FLNB-related disorders include a spectrum of phenotypes ranging from mild (spondylocarpotarsal synostosis [SCT] syndrome and Larsen syndrome) to severe (atelosteogenesis types I [AOI] and III [AOIII], boomerang dysplasia). SCT syndrome is characterized by disproportionate short stature, block vertebrae, scoliosis and lordosis, carpal and tarsal fusion, club feet, hearing loss, dental enamel hypoplasia, and mild facial dysmorphisms. Larsen syndrome is characterized by congenital dislocations of the hip, knee, and elbow; club feet (equinovarus or equinovalgus foot deformities); scoliosis and cervical kyphosis, which can be associated with a cervical myelopathy; short, broad, spatulate distal phalanges; and distinctive craniofacies (prominent forehead, depressed nasal bridge, malar flattening, and widely spaced eyes). Both can have midline cleft palate and conductive hearing loss. AOIII and AOI are characterized by severe short-limbed dwarfism; dislocated hips, knees, and elbows; and club feet. AOI is lethal in the perinatal period.
A rare, autosomal recessive inherited syndrome caused by mutations in the DYM gene. It is characterized by abnormal skeletal development, microcephaly, and intellectual disability.
Acromicric dysplasia is an autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have distinct facial features, including round face, well-defined eyebrows, long eyelashes, bulbous nose with anteverted nostrils, long and prominent philtrum, and thick lips with a small mouth. Other characteristic features include hoarse voice and pseudomuscular build, and there are distinct skeletal features as well, including an internal notch of the femoral head, internal notch of the second metacarpal, and external notch of the fifth metacarpal (summary by Le Goff et al., 2011). Allelic disorders with overlapping skeletal and joint features include geleophysic dysplasia-2 (GPHYSD2; 614185) and the autosomal dominant form of Weill-Marchesani syndrome (608328).
Schmid-type metaphyseal chondrodysplasia is characterized by short stature and bowing of the long bones; radiographic features include widening and irregularity of the growth plates, especially in the distal and proximal femora (summary by Makitie et al., 2005).
Abnormal mineralization of the metaphyseal area of bones.
Kenny-Caffey syndrome is characterized by severe proportionate short stature, cortical thickening and medullary stenosis of the tubular bones, delayed closure of the anterior fontanel, eye abnormalities, and transient hypocalcemia. Patients with autosomal dominant KCS type 2 have normal intelligence (Kenny and Linarelli, 1966; Caffey, 1967; summary by Isojima et al., 2014). See KCS1 (244460) for a discussion of an autosomal recessive form of Kenny-Caffey syndrome.
Craniometadiaphyseal dysplasia (CRMDD) is characterized clinically by macrocephaly with frontal prominence, dental hypoplasia, and increased bone fragility. Diagnostic radiologic features include thin bones in the superior part of calvaria with prominent wormian bones, diaphyseal widening of the long tubular bones in early childhood with wide undermineralized metaphyses in older individuals, widened ribs and clavicles, and broadening of short tubular bones with increased transparency and thin cortices (summary by Dhar et al., 2010).
Pyle disease is characterized by long bones with wide and expanded trabecular metaphyses, thin cortical bone, and bone fragility. Fractures are common in Pyle disease, and fracture lines usually go through the abnormally wide metaphyses, revealing their fragility (summary by Kiper et al., 2016).
The Murk Jansen type of metaphyseal chondrodysplasia is characterized by severe short stature, short bowed limbs, clinodactyly, prominent upper face, and small mandible. Hypercalcemia and hypophosphatemia occur despite the lack of parathyroid abnormalities (summary by Cohen, 2002).
Sclerosteosis is a severe sclerosing bone dysplasia characterized by progressive skeletal overgrowth. Syndactyly is a variable manifestation. The disorder is rare and the majority of affected individuals have been reported in the Afrikaner population of South Africa (summary by Brunkow et al., 2001). Genetic Heterogeneity of Sclerosteosis Sclerosteosis-2 (SOST2; 614305) is caused by mutation in the LRP4 gene (604270) on chromosome 11p11.
An extremely rare chondrodysplastic malformation syndrome with the combination of arachnodactyly, becoming evident at around the age of 10, camptodactyly and scoliosis. A mild facial dysmorphism including a broad nose and flaring nostrils and a mild intellectual disability were also noted. The syndrome has been described once in 3 siblings and is suspected to follow autosomal recessive transmission. There have been no further descriptions in the literature since 1972.
Typical Greig cephalopolysyndactyly syndrome (GCPS) is characterized by preaxial polydactyly or mixed pre- and postaxial polydactyly, true widely spaced eyes, and macrocephaly. Individuals with mild GCPS may have subtle craniofacial findings. The mild end of the GCPS spectrum is a continuum with preaxial polysyndactyly type IV and crossed polydactyly (preaxial polydactyly of the feet and postaxial polydactyly of the hands plus syndactyly of fingers 3-4 and toes 1-3). Individuals with severe GCPS can have seizures, hydrocephalus, and intellectual disability.
Baller-Gerold syndrome (BGS) can be suspected at birth in an infant with craniosynostosis and upper limb abnormality. The coronal suture is most commonly affected; the metopic, lambdoid, and sagittal sutures may also be involved alone or in combination. Upper limb abnormality can include a combination of thumb hypo- or aplasia and radial hypo- or aplasia and may be asymmetric. Malformation or absence of carpal or metacarpal bones has also been described. Skin lesions may appear anytime within the first few years after birth, typically beginning with erythema of the face and extremities and evolving into poikiloderma. Slow growth is apparent in infancy with eventual height and length typically at 4 SD below the mean.
The phenotypic spectrum of SHOX deficiency disorders, caused by haploinsufficiency of the short stature homeobox-containing gene (SHOX), ranges from Leri-Weill dyschondrosteosis (LWD) at the severe end of the spectrum to nonspecific short stature at the mild end of the spectrum. In adults with SHOX deficiency, the proportion of LWD versus short stature without features of LWD is not well defined. In LWD the classic clinical triad is short stature, mesomelia, and Madelung deformity. Mesomelia, in which the middle portion of a limb is shortened in relation to the proximal portion, can be evident first in school-aged children and increases with age in frequency and severity. Madelung deformity (abnormal alignment of the radius, ulna, and carpal bones at the wrist) typically develops in mid-to-late childhood and is more common and severe in females. The phenotype of short stature caused by SHOX deficiency in the absence of mesomelia and Madelung deformity (called SHOX-deficient short stature in this GeneReview) is highly variable, even within the same family.
Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterized by abnormalities of the lens of the eye, proportionate short stature, brachydactyly, and joint stiffness. The ocular problems, typically recognized in childhood, include microspherophakia (small spherical lens), myopia secondary to the abnormal shape of the lens, ectopia lentis (abnormal position of the lens), and glaucoma, which can lead to blindness. Height of adult males is 142-169 cm; height of adult females is 130-157 cm. Autosomal recessive and autosomal dominant WMS cannot be distinguished by clinical findings alone.
A group of disorders characterized by ectodermal-based malformations and neoplastic growths in the skin, nervous system, and other organs.
Facial ANGIOFIBROMA in tuberous sclerosis
A non-neoplastic hamartomatous polyp that arises from the small intestine. It is characterized by the presence of smooth muscle branching bands, and cystic mucosal changes.
Lynch syndrome is characterized by an increased risk for colorectal cancer (CRC) and cancers of the endometrium, stomach, ovary, small bowel, hepatobiliary tract, urinary tract, brain, and skin. In individuals with Lynch syndrome the following lifetime risks for cancer are seen: CRC: 52%-82% (mean age at diagnosis 44-61 years). Endometrial cancer in females: 25%-60% (mean age at diagnosis 48-62 years). Gastric cancer: 6%-13% (mean age at diagnosis 56 years). Ovarian cancer: 4%-12% (mean age at diagnosis 42.5 years; ~30% are diagnosed < age 40 years). The risk for other Lynch syndrome-related cancers is lower, though substantially increased over general population rates.
The PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and Proteus-like syndrome. CS is a multiple hamartoma syndrome with a high risk for benign and malignant tumors of the thyroid, breast, and endometrium. Affected individuals usually have macrocephaly, trichilemmomas, and papillomatous papules, and present by the late 20s. The lifetime risk of developing breast cancer is 85%, with an average age of diagnosis between 38 and 46 years. The lifetime risk for thyroid cancer (usually follicular, rarely papillary, but never medullary thyroid cancer) is approximately 35%. The risk for endometrial cancer may approach 28%. BRRS is a congenital disorder characterized by macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis. PS is a complex, highly variable disorder involving congenital malformations and hamartomatous overgrowth of multiple tissues, as well as connective tissue nevi, epidermal nevi, and hyperostoses. Proteus-like syndrome is undefined but refers to individuals with significant clinical features of PS who do not meet the diagnostic criteria for PS.
Alopecia or hypotrichosis, microcephaly, seizures, and mental retardation. A suggested classification groups this syndrome into three types: Type I. Total alopecia and mental retardation, the main features, in association with microcephaly. Type II. Subtotal alopecia and mental retardation with or without epilepsy. Type III. Subtotal alopecia and psychomotor retardation with microcephaly and epilepsy.
Trichodentoosseous syndrome is an autosomal dominant disorder with complete penetrance characterized by abnormalities involving hair, teeth, and bone (summary by Nguyen et al., 2013).
Pachyonychia congenita (PC) is characterized by hypertrophic nail dystrophy, painful palmoplantar keratoderma and blistering, oral leukokeratosis, pilosebaceous cysts (including steatocystoma and vellus hair cysts), palmoplantar hyperhydrosis, and follicular keratoses on the trunk and extremities.
OMIM differentiates the autosomal dominant (KID syndrome) from
Coffin-Siris syndrome is a multiple malformation syndrome characterized by mental retardation associated with coarse facial features, hypertrichosis, sparse scalp hair, and hypoplastic or absent fifth fingernails or toenails. Other more variable features may include poor overall growth, craniofacial abnormalities, spinal anomalies, and congenital heart defects (review by Vergano and Deardorff, 2014). Mutations in the ARID1B gene are the most common cause of Coffin-Siris syndrome (Wieczorek et al., 2013). Genetic Heterogeneity of Coffin-Siris Syndrome Forms of Coffin-Siris syndrome have been shown to be caused by mutations in genes encoding subunits of the SWI/SNF complex, also known as the BAF complex, which functions as a chromatin remodeling factor. These include CSS2 (614607), caused by mutation in the ARID1A gene (603024); CSS3 (614608), caused by mutation in the SMARCB1 gene (601607); CSS4 (614609), caused by mutation in the SMARCA4 gene (603254); CSS5 (616938), caused by mutation in the SMARCE1 gene (603111); CSS6 (617808), caused by mutation in the ARID2 gene (609539); CSS7 (618027), caused by mutation in the DPF2 gene (601671); and CSS8 (618362), caused by mutation in the SMARCC2 gene (601734). A similar phenotype, Nicolaides-Baraitser syndrome (NCBRS; 601358), is also caused by mutation in a subunit of this complex, i.e., SMARCA2 (600014).
Microcephaly, characteristic facies (swelling, p prominent supraorbital ridges and narrow palpebral fissures), obesity, epilepsy, and hypogonadism, and mental deficiency.
Axenfeld-Rieger syndrome is primarily an eye disorder, although it can also affect other parts of the body. This condition is characterized by abnormalities of the front part of the eye, an area known as the anterior segment. For example, the colored part of the eye (the iris), may be thin or poorly developed. The iris normally has a single central hole, called the pupil, through which light enters the eye. People with Axenfeld-Rieger syndrome often have a pupil that is off-center (corectopia) or extra holes in the iris that can look like multiple pupils (polycoria). This condition can also cause abnormalities of the cornea, which is the clear front covering of the eye.About half of affected individuals develop glaucoma, a serious condition that increases pressure inside the eye. When glaucoma occurs with Axenfeld-Rieger syndrome, it most often develops in late childhood or adolescence, although it can occur as early as infancy. Glaucoma can cause vision loss or blindness.The signs and symptoms of Axenfeld-Rieger syndrome can also affect other parts of the body. Many affected individuals have distinctive facial features such as widely spaced eyes (hypertelorism); a flattened mid-face with a broad, flat nasal bridge; and a prominent forehead. The condition is also associated with dental abnormalities including unusually small teeth (microdontia) or fewer than normal teeth (oligodontia). Some people with Axenfeld-Rieger syndrome have extra folds of skin around their belly button (redundant periumbilical skin). Other, less common features can include heart defects, the opening of the urethra on the underside of the penis (hypospadias), narrowing of the anus (anal stenosis), and abnormalities of the pituitary gland that can result in slow growth.Researchers have described at least three types of Axenfeld-Rieger syndrome. The types, which are numbered 1 through 3, are distinguished by their genetic cause.
Cerebrocostomandibular syndrome (CCMS) is characterized mainly by severe micrognathia, rib defects, and mental retardation. A spectrum of rib gap defects have been reported ranging from a few dorsal rib segments to complete absence of ossification. In about half of the 65 reported cases to date, there is cerebral involvement including mental retardation, microcephaly, and histologic anomalies. Both autosomal dominant and autosomal recessive forms of the disorder have been described (Zeevaert et al., 2009). See CDG2G (611209) for a cerebrocostomandibular-like syndrome.
Spondylocostal dysostosis (SCDO), defined radiographically as multiple segmentation defects of the vertebrae (M-SDV) in combination with abnormalities of the ribs, is characterized clinically by: a short trunk in proportion to height; short neck; non-progressive mild scoliosis in most affected individuals, and occasionally, more significant scoliosis. Respiratory function in neonates may be compromised by reduced size of the thorax. By age two years lung growth may improve sufficiently to support relatively normal growth and development; however, even then life-threatening complications can occur, especially pulmonary hypertension in children with severely restricted lung capacity from birth. Males with SCDO appear to be at increased risk for inguinal hernia.
INSR-related severe syndromic insulin resistance comprises a phenotypic spectrum that is a continuum from the severe phenotype Donohue syndrome (DS) (also known as leprechaunism) to the milder phenotype Rabson-Mendenhall syndrome (RMS). DS at the severe end of the spectrum is characterized by severe insulin resistance (hyperinsulinemia with associated fasting hypoglycemia and postprandial hyperglycemia), severe prenatal growth restriction and postnatal growth failure, hypotonia and developmental delay, characteristic facies, and organomegaly involving heart, kidneys, liver, spleen, and ovaries. Death usually occurs before age one year. RMS at the milder end of the spectrum is characterized by severe insulin resistance that, although not as severe as that of DS, is nonetheless accompanied by fluctuations in blood glucose levels, diabetic ketoacidosis, and – in the second decade – microvascular complications. Findings can range from severe growth delay and intellectual disability to normal growth and development. Facial features can be milder than those of DS. Complications of longstanding hyperglycemia are the most common cause of death. While death usually occurs in the second decade, some affected individuals live longer.
Lymphedema-distichiasis syndrome (referred to as LDS in this GeneReview) is characterized by lower-limb lymphedema, and distichiasis (aberrant eyelashes ranging from a full set of extra eyelashes to a single hair). Lymphedema typically appears in late childhood or puberty, is confined to the lower limbs with or without involvement of the external genitalia, and is often asymmetric; severity varies within families. Males develop edema at an earlier age and have more problems with cellulitis than females. Distichiasis, which may be present at birth, is observed in 94% of affected individuals. About 75% of affected individuals have ocular findings including corneal irritation, recurrent conjunctivitis, and photophobia; other common findings include varicose veins and ptosis.
CHARGE is a mnemonic for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies. CHARGE syndrome is characterized by the following: Unilateral or bilateral coloboma of the iris, retina-choroid, and/or disc with or without microphthalmos (80%-90% of individuals). Unilateral or bilateral choanal atresia or stenosis (50%-60%). Cranial nerve dysfunction resulting in hyposmia or anosmia, unilateral or bilateral facial palsy (40%), impaired hearing, and/or swallowing problems (70%-90%). Abnormal outer ears, ossicular malformations, Mondini defect of the cochlea and absent or hypoplastic semicircular canals (>90%). Cryptorchidism in males and hypogonadotropic hypogonadism in both males and females. Developmental delay. Cardiovascular malformations (75%-85%). Growth deficiency (70%-80%). Orofacial clefts (15%-20%). Tracheoesophageal fistula (15%-20%). Neonates with CHARGE syndrome often have multiple life-threatening medical conditions. Feeding difficulties are a major cause of morbidity in all age groups.
A teratogenic disorder observed in a newborn or child of a mother who was exposed to phenytoin during pregnancy. Manifestations include dysmorphic craniofacial features, hypoplastic distal phalanges and nails, growth delay and delayed psychomotor development.
A pattern of abnormalities in infants born to epileptic mothers who were treated during their pregnancies with trimethadione anticonvulsant drugs. The abnormalities include developmental delay, craniofacial dysmorphism (midfacial flattening, V-shaped eyebrows, short nose, synophrys, malformed ears, and strabismus), cardiovascular abnormalities, absent kidney and ureter, omphalocele, meningocele, and other defects.
A teratogenic disorder observed in a newborn or child of a mother who was exposed to warfarin during pregnancy. Manifestations include nasal bridge depression, nasal bones hypoplasia, microcephaly, congenital heart disorders, and brachydactyly.
Deletion of the long arm of chromosome 4 with a variable phenotype consisting mainly of delayed psychomotor development, craniofacial anomalies, cardiovascular defects, skeletal abnormalities, occasional cleft palate, micrognathia, and glossoptosis (Pierre Robin sequence) and other disorders. Rieger anomaly (malformations of the anterior chamber of the eye and the teeth) occurs in some cases.
A syndrome in which parts of both ends of chromosome 4 have been lost (deletion) and the two broken ends reunited to form a ring-shaped figure. Clinical manifestations vary according to the breakpoints and their distance to the telomeres and include developmental delay and neurological, craniofacial, skeletal, genitourinary, and cutaneous anomalies, some of which overlap those of Seckel and Wolf-Hirschhorn syndromes.
Deletion of the long arm of chromosome 7 with delayed mental and physical development and multiple anomalies involving the craniofacial structures, eyes, extremities (mainly split hand/split foot abnormality), and other parts.
A rare chromosomal anomaly syndrome resulting from a partial deletion of the short arm of chromosome 9. The syndrome has a highly variable phenotype with typical characteristics of intellectual disability, craniofacial dysmorphism (trigonocephaly, upslanting palpebral fissures, hypoplastic supraorbital ridges), abnormal digits (long middle phalanges with short distal phalanges), as well as frequent association with genitourinary abnormalities (cryptorchidism, hypospadias, ambiguous genitalia, 46,XY testicular dysgenesis). Congenital hypothyroidism and cardiovascular defects have been reported in some cases. Patients present an increased risk for gonadoblastoma.
Duplication of the short arm of chromosome 9 with psychomotor retardation, hypertelorism, deep-set eyes, downslanting palpebral fissures, large nose, short upper lip, down-curved corners of the mouth, cup-shaped ears, kyphoscoliosis, small hands and feet, characteristic dermatoglyphic patterns, and cryptorchidism.
A syndrome in which both ends of chromosome 10 have been lost (deletion) and the two broken ends have reunited to form a ring-shaped figure. Psychomotor retardation, craniofacial abnormalities (mainly microcephaly and eye and nose deformities), hypoplastic male genitalia, transverse palmar creases, and occasional heart anomalies are the usual abnormalities.
Pallister-Killian syndrome is a dysmorphic condition involving most organ systems, but also characterized by a tissue-limited mosaicism; most fibroblasts have 47 chromosomes with an extra small metacentric chromosome, whereas the karyotype of lymphocytes is normal. The extra metacentric chromosome is an isochromosome for part of the short arm of chromosome 12: i(12)(p10) (Peltomaki et al., 1987; Warburton et al., 1987).
A rare syndrome that is characterized by the partial deletion of the long arm of chromosome 13. Signs and symptoms include low birth weight, craniofacial malformations, hands and feet malformations, and mental and psychomotor retardation.
Chromosome 18 in which both ends have been lost (deletion) and the broken ends have reunited to form a ring-shaped figure, usually associated with mental retardation, craniofacial dysmorphism, and limb deformities, and other defects.
A rare chromosomal anomaly syndrome with a highly variable phenotype ranging from normal (in the majority of cases) to a mild, subtle phenotype. Principle characteristics are spinal abnormalities (stenosis, vertebral fusion, and kyphosis), hypotonia, lifelong constipation, sloped shoulders, skin pigmentation abnormalities (linear and whorled nevoid hypermelanosis) and significant learning disabilities despite normal intelligence. More severe phenotypes, with patients presenting psychomotor and speech delay, mild facial dysmorphism, cardiac (ventricular septal defect, dysplastic tricuspid mitral valve) and renal anomalies (horseshoe kidneys) have also been reported.
Ring chromosome 20 syndrome is a condition that affects the normal development and function of the brain. The most common feature of this condition is recurrent seizures (epilepsy) in childhood. The seizures may occur during the day or at night during sleep. They are described as partial seizures because they affect only one area of the brain, a region called the frontal lobe. In many cases, the seizures are complex and resistant to treatment with anti-epileptic drugs. Prolonged seizure episodes known as non-convulsive status epilepticus also appear to be characteristic of ring chromosome 20 syndrome. These episodes involve confusion and behavioral changes.Most people with ring chromosome 20 syndrome also have some degree of intellectual disability and behavioral difficulties. Although these problems can appear either before or after the onset of epilepsy, they tend to worsen after seizures develop. Additional features of this condition can include slow growth and short stature, a small head (microcephaly), and subtle differences in facial features. Major birth defects are rarely seen with ring chromosome 20 syndrome.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 22 in somatic cells.
Cat eye syndrome (CES) is characterized clinically by the combination of coloboma of the iris and anal atresia with fistula, downslanting palpebral fissures, preauricular tags and/or pits, frequent occurrence of heart and renal malformations, and normal or near-normal mental development. A small supernumerary chromosome (smaller than chromosome 21) is present, frequently has 2 centromeres, is bisatellited, and represents an inv dup(22)(q11).
A rare sex chromosome abnormality in which a female child has 3 extra X chromosomes.
A rare sex chromosome abnormality in which a male child has 2 extra X chromosomes.
A sex chromosome aneuploidy with an incidence of 1 in 85,000 male births. Principal findings include radioulnar synostosis, hypogonadism, mental retardation, and speech disorders. Associated disorders ara variable and may include characteristic facies, multiple skeletal abnormalities, and cardiac and genital malformations. Many features are similar to those seen in the Klinefelter syndrome (chromosome XXY syndrome), hence the synonym Klinefelter variant.
An osteoma that develops in the medullary cavity of the bone.
A lamellar pattern visible on radiographs and mainly localized at the metaphyses of the long tubular bones. Pathologic-anatomical studies revealed that these benign signs on x-rays are the result of a juvenile metaphyseal bone necrosis. Calcifications in the necrotic marrow lead to this lamellar or lattice-like appearance.
Buschke-Ollendorff syndrome is an autosomal dominant connective tissue disorder manifest by multiple subcutaneous nevi or nodules. They may be either elastin-rich (elastoma) or collagen-rich (dermatofibrosis lenticularis disseminata) on histologic examination. The lesions are usually nontender and firm. Affected individuals also have osteopoikilosis (OPK), literally meaning 'spotted bones,' which are osteosclerotic foci that occur in the epiphyses and metaphyses of long bones, wrist, foot, ankle, pelvis, and scapula. Some individuals have both skin and bone manifestations, whereas others may lack skin or bone manifestations. Some individuals may also have melorheostosis (155950), which is characterized by 'flowing' hyperostosis of the cortex of tubular bones. Most reported cases of BOS and OPK are benign, and the bone lesions are found incidentally, although some patients may have joint pain (reviews by Hellemans et al., 2004 and Zhang et al., 2009).
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape. [pmid:19125436]
Premature fusion of the sagittal suture.
A congenital abnormality characterized by round or oval shaped defects in the membranous skull vault resulting in non-ossified, honey comb-like areas in the calvaria.
A congenital abnormality characterized by the failure of the bones of the skull to close.
Partial absence of a free limb (excluding girdle). It can refer to the proximal, middle or distal segment of the upper or lower limb. The deficiency may be transverse or longitudinal. Thus, meromelia is a lack of a part, but not all, of one or more limbs with the presence of a hand or foot.
Congenital duplication of all or part of a limb.
Macrodactyly is a congenital anomaly characterized by fibrofatty tissue enlargement and bony overgrowth in affected digits with resultant loss of function. Macrodactyly affects a 'nerve territory,' and the individual peripheral nerve is both enlarged and elongated (summary by Rios et al., 2013).
A rare anatomical malformation characterized by polydactyly (extra fingers or toes) and syndactyly (webbed fingers or toes).
A condition in which middle parts of the hands and/or feet (digits and meta-carpals and -tarsals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic 3rd toe/fingers over absent 2nd or 3rd toes/fingers as far as oligo- or monodactyl hands and/or feet.
Acheiropody is characterized by bilateral congenital amputations of the upper and lower extremities and aplasia of the hands and feet. Specific patterns of malformations consist of a complete amputation of the distal epiphysis of the humerus, amputation of the distal part of the tibial diaphysis, and aplasia of the radius, ulna, fibula, and of the carpal, metacarpal, tarsal, metatarsal, and phalangeal bones (summary by Ianakiev et al., 2001).
A dislocation of the head of the radius from its socket in the elbow joint.
Missing or malformed long bones of the upper limbs with the distal parts (the hands) connected to the variably shortened or even absent upper extremity, leading to a flipper-like appearance, as opposed to other forms of limb malformations were either the whole limb is missing (such as amelia), or the distal part of a limb is absent (peromelia).
The total absence of the hand, with no bony elements distal to the radius or ulna.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the thumb. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
The presence of more than the normal number of carpal bones.
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Any anatomic abnormality of the hip that is present at the time of birth.
The total absence of the foot, with no bony elements distal to the tibia or fibula.
Phocomelia affecting only the lower limbs.
A deformity of foot and ankle in which the foot is bent down and outwards.
A congenital deformity characterized by a dorsiflexed, inverted, and adducted foot, i.e., a combination of talipes calcaneus and talipes varus.
The metatarsals are deviated medially (tibially), that is, the bones in the front half of the foot bend or turn in toward the body.
Angulation of the first metatarsal bone towards the midline. This is associated with angulation of the phalanges of the same toe away from the midline (HALLUX VALGUS).
Congenital, complete or partial fusion of the TARSAL BONES of the foot. PES PLANUS is usually a feature.
Webbing or fusion of the toes, involving soft parts only or including bone structure. Bony fusions are referred to as ""bony"" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the toes in a proximo-distal axis are referred to as ""Symphalangism"".
A condition characterized by non-union of the tibia, which is present at birth. It is usually associated with neurofibromatosis type 1.
A developmental defect that occurs if the two halves of the patella fail to fuse in early childhood.
An abnormally increased curvature of the thoracic portion of the spine that is present at the time of birth.
Abnormal sideways curvature of the spine that is present at birth.
A congenital abnormality characterized by incomplete development of one side of the vertebrae (arch and hemicentrum), resulting in spinal malformation.
A bifid rib refers to cleavage of the sternal end of a rib, usually unilateral. Bifid ribs are usually asymptomatic, and are often discovered incidentally by chest x-ray.
The sternal cleft is a rare congenital anomaly resulting from a fusion failure of the sternum.
An anterior retrosternal or parasternal hernia that can result in the herniation of liver or intestines into the chest cavity.
A posterolateral defect in the diaphragm, commonly referred to as a Bochdalek hernia, which is often accompanied by herniation of the stomach, intestines, liver, and/or spleen into the chest cavity.
Gastroschisis is a congenital defect of the abdominal wall that occurs laterally to, and often to the right of, a normally closed umbilical ring. Visceral organs that herniate through the defect are not covered by a membrane. Gastroschisis is distinct from omphalocele (164750), which is characterized by herniation of abdominal contents through the base of the umbilical cord; in omphalocele, the visceral organs are covered by membranes (summary by Mastroiacovo et al., 2007). Both omphalocele and gastroschisis, when they occur without other malformations, are probably multifactorial (Baird and MacDonald, 1981).
An abnormality of the nose. [HPO:probinson]
Complete absence of all nasal structures.
A congenital malformation of the larynx in which there is failure of recanalization of the laryngotracheal tube during gestation.
A rare congenital malformation in the larynx. It is characterized by the presence of an air-filled sac within the laryngeal wall which may bulge on the neck.
A congenital absence or considerable underdevelopment of the trachea such that communication between the larynx proximally and the alveoli of the lungs distally is lacking.
A developmental anomaly characterised by focal obliteration of the proximal segment of a bronchus. The bronchial pattern is entirely normal distal to the site of stenosis.
An uncommon congenital abnormality characterized by either lethal complete absence of the lungs or varying degrees of underdevelopment of the lung parenchyma. It may be associated with other congenital abnormalities.
A congenital abnormality in which the lung parenchyma is not fully developed. It may be associated with other congenital abnormalities.
A small lobe sometimes found on the upper part of the right lung, formed by an infolding of the pleura and separated from the rest of the upper lobe by a deep groove lodging the azygos vein.
A rare abnormality in the lungs that is present at birth. It is characterized by hyperinflation of one or more lobes of the lungs. Signs and symptoms appear early in life and include dyspnea, wheezing, and cyanosis.
A congenital defect of heart development characterized by origin of both pulmonary artery and aorta from the morphological left ventricle.
Refers to the specific combination of defects with a severely dysplastic pulmonary valve and massively dilated branch pulmonary arteries.
Dysfunction of the pulmonary valve characterized by incomplete valve closure that is present at birth.
Congenital defect characterized by underdevelopment of the tricuspid valve.
A congenital disorder of the aortic valve in which the orifice of the valve fails to develop.
Underdevelopment of the right-sided structures of the heart.
Uhl anomaly of the right ventricle refers to the almost complete absence of right ventricular myocardium, normal tricuspid valve, and preserved septal and left ventricular myocardium.
Mesocardia is a abnormal location of the heart in which the heart is in a midline position and the longitudinal axis of the heart lies in the mid-sagittal plane.
A developmental defect in which the coronary sinus fails to form. [HPO:nvasilevsky, PMID:24551710]
Narrowing or constriction of the aorta localized proximal to the ductus arteriosus, i.e., to the preductal region of aortic arch.
Narrowing or constriction of the aorta localized distal to the ductus arteriosus, i.e., to the postductal region of aortic arch.
An underdeveloped aortic arch that is present at birth. This symptom is usually found in association with other cardiac defects that characterize left heart syndrome.
A conenital abnormality of the aortic arch in which the two embryonic aortc arches form a vascular ring that surrounds the trachea or esophagus and then join to form the descending aorta. Double aortic arch can cause symptoms because of compression of the esophagus (dysphagia, cyanosis while eating) or trachea (stridor).
A patent ductus arteriosus or ductal ligament completes the ring.
A congenital anatomic anomaly in which the aorta is positioned directly above a ventricular septal defect, thus receiving blood from both the right and left ventricles, resulting in an overall decrease In oxygenated haemoglobin and tissue cyanosis.
A congenital malformation with abnormal connection between one of the coronary arteries and a heart chamber or another blood vessel.
An abnormal origin of the left circumflex artery (LCX) from the right coronary artery. Normally, the left anterior descending (LAD) and the LCX arise from a common stem, the left main coronary artery (LMCA).
A congenital defect with aplasia (absence) of one of the right or left pulmonary artery.
A congenital anomaly with a narrowing or complete absence of the opening between the right ventricle and the pulmonary artery. [HPO:probinson]
Underdevelopment of the pulmonary artery.
A congenital cardiovascular abnormality characterized by the narrowing of the lumen of the main pulmonary artery or its branches. It may be associated with other congenital heart malformations. Signs and symptoms include dyspnea, tachypnea, tachycardia, fatigue, and edema.
Aberrant drainage of one or more of the pulmonary veins which causes the return of oxygen-rich blood to the right atrium.
A rare congenital vascular anomaly that results when the left superior cardinal vein caudal to the innominate vein fails to regress.
A rare genetic chronic skin disorder characterized by hyperkeratosis and transient erythema. Mutations in GJB3 and GJB4 genes have been identified as causative agents.
Netherton syndrome is a rare and severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Generalized scaly erythroderma is apparent at or soon after birth and usually persists. Scalp hair is sparse and brittle with a characteristic 'bamboo' shape under light microscopic examination due to invagination of the distal part of the hair shaft to its proximal part. Atopic manifestations include eczema-like rashes, atopic dermatitis, pruritus, hay fever, angioedema, urticaria, high levels of IgE in the serum, and hypereosinophilia. Life-threatening complications are frequent during the neonatal period, including hypernatremic dehydration, hypothermia, extreme weight loss, bronchopneumonia, and sepsis. During childhood, failure to thrive is common as a result of malnutrition, metabolic disorders, chronic erythroderma, persistent cutaneous infections, or enteropathy (summary by Bitoun et al., 2002).
Vohwinkel syndrome is a disorder with classic and variant forms, both of which affect the skin.In the classic form of Vohwinkel syndrome, affected individuals have thick, honeycomb-like calluses on the palms of the hands and soles of the feet (palmoplantar keratoses) beginning in infancy or early childhood. Affected children also typically have distinctive starfish-shaped patches of thickened skin on the tops of the fingers and toes or on the knees. Within a few years they develop tight bands of abnormal fibrous tissue around their fingers and toes (pseudoainhum); the bands may cut off the circulation to the digits and result in spontaneous amputation. People with the classic form of the disorder also have hearing loss.The variant form of Vohwinkel syndrome does not involve hearing loss, and the skin features also include widespread dry, scaly skin (ichthyosis), especially on the limbs. The ichthyosis is usually mild, and there may also be mild reddening of the skin (erythroderma). Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life.
Dyskeratosis congenita (DC), a telomere biology disorder, is characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia. The classic triad may not be present in all individuals. People with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome). Onset and progression of manifestations of DC vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.
Hereditary benign intraepithelial dyskeratosis (HBID) is a rare inherited disease characterized by elevated plaques on the ocular and oral mucous membranes. The bulbar conjunctiva is involved, especially in the nasal and temporal perilimbal region. Dilated superficial vessels in association with the conjunctival plaques give the eye an overall red appearance, which accounts for the disease's nickname of 'red eye.' Morphologically, the lesions consist of a dyskeratotic hyperplastic epithelium. The oral lesions, which are typically asymptomatic and may go unrecognized, usually appear as thick, soft, white papules and plaques of various sizes, involving any part of the oral cavity. The ocular manifestations in this condition vary in severity from asymptomatic plaques on the bulbar conjunctiva to complete involvement of the cornea with severe vision loss. Patients commonly complain of symptoms of irritation, such as erythema, itching, excessive lacrimation, and photophobia. Periods of acute intensification of symptoms are common, especially in the spring. The lesions may become apparent in early infancy and may date from birth. The plaques persist throughout life and sometimes progress, but may wax and wane (summary by Witkop et al., 1960; Reed et al., 1979; and Baroni et al., 2009).
Acrokeratosis verruciformis of Hopf is a localized disorder of keratinization affecting the distal extremities. Onset occurs early in life (Dhitavat et al., 2003).
A benign focal growth composed of vascular tissue.
Birthmarks are abnormalities of the skin that are present when a baby is born. There are two types of birthmarks. Vascular birthmarks are made up of blood vessels that haven't formed correctly. They are usually red. Two types of vascular birthmarks are hemangiomas and port-wine stains. Pigmented birthmarks are made of a cluster of pigment cells which cause color in skin. They can be many different colors, from tan to brown, gray to black, or even blue. Moles can be birthmarks. No one knows what causes many types of birthmarks, but some run in families. Your baby's doctor will look at the birthmark to see if it needs any treatment or if it should be watched. Pigmented birthmarks aren't usually treated, except for moles. Treatment for vascular birthmarks includes laser surgery. . Most birthmarks are not serious, and some go away on their own. Some stay the same or get worse as you get older. Usually birthmarks are only a concern for your appearance. But certain types can increase your risk of skin cancer. If your birthmark bleeds, hurts, itches, or becomes infected, call your health care provider.
A poorly circumscribed neoplasm arising from the soft tissues in infants. It is characterized by the presence of bland fibroblastic spindle cells, collagenous stroma formation, primitive mesenchymal round cells, and mature fat cells. These components combined form a distinct organoid pattern.
A capillary vascular anomaly that is characterized by hypopigmented macules.
A bluish-gray to gray-brown benign, melanocytic nevus found usually in the LUMBOSACRAL REGION of dark-skinned people, especially those of East Asian ancestry. It is usually congenital or appears shortly after birth, and disappears in childhood.
Nevus comedonicus (NC) is a rare type of epidermal nevus with predilection for the face and neck area. The condition develops within the first decade of life in most patients. NC is characterized by dilated, plugged follicular ostia containing lamellar keratinaceous material and grouped in a honeycomb pattern; the distribution of lesions may be unilateral, bilateral, linear, interrupted, segmental, or along the lines of Blaschko. NC may be nonpyogenic with an acne-like appearance or associated with the formation of cysts, papules, pustules, and abscesses. Histologically, the lesions are large, grouped, dilated follicular ostia devoid of hair shafts but filled with keratin layers (summary by Tchernev et al., 2013).
A congenital condition characterized by the absence of hair on the scalp or entire body. The lack of hair is rarely absolute and is usually accompanied by incompletely grown, lanugo-like hair. It affects males twice as much as females and a familial tendency is common.
Koilonychia, or 'spoon nails,' is a relatively uncommon disorder in which the nails are abnormally thin and concave from side to side, with the edges turned up. Single or multiple fingers and/or toes may be involved (summary by Bumpers and Bishop, 1980). Koilonychia is referred to here as nonsyndromic congenital nail disorder-2 (NDNC2). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
The presence of fibromata beneath finger or toenails.
Bart-Pumphrey syndrome is characterized by nail and skin abnormalities and hearing loss.People with Bart-Pumphrey syndrome typically have a white discoloration of the nails (leukonychia); the nails may also be thick and crumbly. Affected individuals often have wart-like (verrucous) skin growths called knuckle pads on the knuckles of the fingers and toes. They may also have thickening of the skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). The skin abnormalities generally become noticeable during childhood.The hearing loss associated with Bart-Pumphrey syndrome ranges from moderate to profound and is typically present from birth (congenital).The signs and symptoms of this disorder may vary even within the same family; while almost all affected individuals have hearing loss, they may have different combinations of the other associated features.
Bjornstad syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and pili torti. The hearing loss is congenital and of variable severity. Pili torti (twisted hairs), a condition in which the hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair very brittle, is usually recognized early in childhood (Selvaag, 2000).
Failure to develop and congenital absence of the breast.
Congenital structural abnormalities of the DIGESTIVE SYSTEM.
A spherical hollow structure with a smooth muscle coat, lined by a mucous membrane, and attached to any part of the gastrointestinal tract, from the base of the tongue to the anus.
Mulberry molars are irregular teeth generally affecting the first molars and are characterized by a grossly deformed crown imitating, as the name implies, the surface of a mulberry.
A supernumerary tooth located near the midline of the dental arch between two central incisors.
The development of two teeth from a single tooth bud, leading to a larger fused tooth.
Increased size of the teeth, which can be defined as a mesiodistal tooth diameter (width) more than 2 SD above mean for age. Alternatively, an apparently increased maximum width of the tooth.
An abnormal conical form of the teeth, that is, a tooth whose sides converge or taper together incisally. [HPO:ibailleulforestier]
Increased volume of dental pulp of permanent molar.
Persistence of the primary teeth beyond the age by which they normally are shed and replaced by the permanent teeth.
Loss of the primary (also known as deciduous) teeth before the usual age.
Premature tooth eruption, which can be defined as tooth eruption more than 2 SD earlier than the mean eruption age.
A condition in which certain opposing teeth fail to establish occlusal contact when the jaws are closed.
Increased superior-inferior overlap of the maxillary central incisors over the mandibular central incisors relative to the incisal ridges.
Abnormally increased dimension of the maxilla, especially relative to the mandible, resulting in a malocclusion or malalignment between the upper and lower teeth or in anterior positioning of the nasal base, increased convexity of the face, increased nasolabial angle, or increased width (transverse dimension of the maxilla.
A congenital abnormality consisting of a fissure in the midline of the lip and upper jaw.
A congenital abnormality consisting of a fissure in the midline of the lip, hard and/or soft palate and upper jaw.
Tongue with a median apical indentation or fork.
A split or cleft in the uvula resulting from incomplete fusion of the palatine shelves.
A structural abnormality of the esophagus.
A congenital abnormality characterized by the presence of a duplicated segment of the esophagus. The duplicated segment may by tubular or cystic.
Congenital tracheoesophageal fistula without esophageal atresia.
A developmental anomaly wtih a small tubular or saccular midline stomach.
A developmental disorder in which there is a duplication the entire intestine or of a portion of the intestine.
A congenital malformation characterized by the absence of a normal opening in a part of the small intestine.
A congenital malformation characterized by the absence of a normal opening in a part of the duodenum.
Jejunal atresia is the most common cause of bowel obstruction in the newborn. In this condition, because of agenesis of the mesentery, the distal small bowel comes straight off the caecum and twists around the marginal artery, suggesting a maypole, a Christmas tree, or an apple peel at operation. Obliteration of the superior mesenteric artery may underlie this malformation.
A congenital malformation characterized by the absence of a normal opening in a part of the ileum.
Dilation and elongation of the duodenum with hypertrophy of all layers of the duodenum.
A congenital malformation characterized by the absence of a normal opening in a part of the colon.
An anatomical anomaly that results from an abnormal rotation of the gut as it returns to the abdominal cavity during embryogenesis.
An abnormaltiy of the rectum, the final segment of the large intestine that stores solid waste until it passes through the anus.
A congenital abnormality in which the rectum, vagina, and urethra fuse and form a common channel.
Abnormal displacement or malposition of the anus.
A developmental defect in which the gallbladder fails to form. [DDD:hfirth]
Absence of the liver owing to a failure of the liver to develop.
A congenital anomaly of the pancreas that results from failed fusion of the dorsal and ventral ducts during embyological development. Three variants have been described: type 1 or classical divisum in which there is total failure of fusion; type 2 in which dorsal drainage is dominant in the absence of the duct of Wirsung; and type 3 or incomplete divisum where a small communicating branch is present.
Absent development of the adrenal gland.
Abnormal anatomical location of the adrenal gland.
A condition characterized by the presence of rudimentary THYROID tissue at the base of the TONGUE. It is due to failed embryonic development and migration of thyroid tissue to its normal location. The lingual thyroid usually cannot maintain adequate hormone production thereby resulting in HYPOTHYROIDISM.
A congenital abnormality characterized by the presence of only one kidney.
A congenital anomaly of the urinary tract, in which the kidney is duplicated and is drained via two separate renal pelves and ureters.
A congenital abnormality of the kidney characterized by the presence of two separate pelvicocaliceal systems with a single or duplex ureter.
abnormal increase in the number of otherwise normal cells in the kidney without tumor formation that leads to kidney enlargement; it differs from hypertrophy, which is an increase in bulk of the kidney without an increase in the number of cells.
A congenital renal disorder characterized by the presence of small cysts in the renal cortex and/or renal medulla.
A developmental defect characterized by absence or poor development of proximal renal tubules.
Collection of urine in the renal pelvis that results in dilatation of the renal pelvis and calyces that is present at birth.
Isolated enlargement of renal calyces without obstruction.
Dilatation of the ureter caused by obstruction of urine flow that is present at birth.
A developmental disturbance with extreme ureteral dilatation.
A congenital anomaly in which the ureteral orifice drains into an abnormal location.
Complete or partial blockage of the ureter at the point where it enters the bladder that is present at birth.
The presence of an abnormal membrane obstructing the urethra.
A congenital abnormality that results from the failure of the lumen of urachus to be obliterated. It presents with leakage of urine from the bladder through the umbilicus.
A gonad that contains both ovarian follicles and testicular tubular elements.
A genital phenotype that is not clearly assignable to a single gender. Ambiguous genitalia can be evaluated using the Prader scale: Prader 0: Normal female external genitalia. Prader 1: Female external genitalia with clitoromegaly. Prader 2: Clitoromegaly with partial labial fusion forming a funnel-shaped urogenital sinus. Prader 3: Increased phallic enlargement. Complete labioscrotal fusion forming a urogenital sinus with a single opening. Prader 4: Complete scrotal fusion with urogenital opening at the base or on the shaft of the phallus. Prader 5: Normal male external genitalia. The diagnosis of ambiguous genitalia is made for Prader 1-4.
Aplasia, that is failure to develop, of the ovary.
Undescended or ectopic ovaries are characterized by the attachment of the upper pole of the ovary to an area above the level of the common iliac vessels.
A developmental disorder characterized by the progressive loss of primordial germ cells in the developing ovaries of an embryo, leading to hypoplastic ovaries composed of wavy connective tissue with occasional clumps of granulosa cells, and frequently mesonephric or hilar cells.
The presence of a supernumerary Fallopian tube.
A congenital abnormality characterized by the complete absence of the uterus.
A malformation of the uterus in which the uterus is present as a paired organ as a result of the failure of fusion of the mullerian ducts during embryogenesis. [HPO:probinson]
The presence of a vaginal septum, thereby creating a vaginal duplication. The septum is longitudinal in the majority of cases.
A congenital birth defect characterized by the absence of a normal vaginal opening.
An anomaly of the testicle (the male gonad).
The testicular regression syndrome (TRS) was delineated by Sarto and Opitz (1973), who called it the XY gonadal dysgenesis syndrome. It is characterized primarily by the absence of gonads in an XY person. In most cases, uterus and fallopian tubes are absent but small tubular structures interpreted as mullerian or wolffian rudiments (or both) are present. The range of virilizing effects due to early testicular tissue extends from none in phenotypic females with only slightly hypoplastic normal external genitalia, well-formed but hypoplastic uterus, and well-formed tubes (De Marchi et al., 1981) to the anorchic phenotypic male (Edman et al., 1977). Most affected individuals lack a vagina but a urogenital sinus or pseudovaginal urethral outpouching is found. Partial labioscrotal fusion and clitoris enlargement are common, breast development is absent, and postpubertal eunuchoid habitus is the rule. Sometimes nongenital anomalies are present (summary by Rosenberg et al., 1984).
Leydig cell hypoplasia is an autosomal recessive disorder in which loss of function of the LHCGR gene in the male prevents normal sexual development. Two types of LCH have been defined (Toledo, 1992). Type I, a severe form caused by complete inactivation of LHCGR, is characterized by complete 46,XY male pseudohermaphroditism, low testosterone and high LH levels, total lack of responsiveness to LH/CG challenge, lack of breast development, and absent development of secondary male sex characteristics. Type II, a milder form caused by partial inactivation of the gene, displays a broader range of phenotypic expression ranging from micropenis to severe hypospadias. Females with inactivating mutations in the LHCGR gene display a mild phenotype characterized by defective follicular development and ovulation, amenorrhea, and infertility (review by Themmen and Huhtaniemi, 2000). Reviews Arnhold et al. (2009) noted that the clinical manifestations of female patients with hypogonadotropic hypogonadism due to isolated LH deficiency (HH23; 228300) are very similar to those of women with hypergonadotropic hypogonadism due to inactivating mutations of the LH receptor: all have female external genitalia, spontaneous development of normal pubic hair and breasts at puberty, and normal to late menarche followed by oligoamenorrhea and infertility. Pelvic ultrasound shows a small or normal uterus and normal or enlarged ovaries with cysts. However, women with LHB (152780) mutations can be treated with luteinizing hormone or chorionic gonadotropin (CG; 118860) replacement therapy; women with LH receptor mutations are resistant to LH, and no treatment is effective in recovering their fertility.
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Aplasia (congenital absence) of the vas deferens.
Abnormal closure or blockage of the vas deferens.
Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it to develop abnormally. Sometimes it's a genetic problem. In other cases, exposure to certain medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, abnormally small or large, or not fully developed. Treatment depends upon the problem. In many cases, treatment only helps with symptoms. It may include antiseizure medicines, shunts to drain fluid from the brain, and physical therapy. There are head malformations that do not involve the brain. Craniofacial disorders are the result of abnormal growth of soft tissue and bones in the face and head. It's common for new babies to have slightly uneven heads, but parents should watch the shape of their baby's head for possible problems. NIH: National Institute of Neurological Disorders and Stroke.
A congenital abnormality characterized by the extrusion of the brain outside of the skull.
A congenital neural tube closure defect resulting in the protrusion of the brain and meninges through a skull opening.
A rare genetic brain malformation characterized by smooth folds and grooves in the brain. There are approximately 20 different types of lissencephaly that are identified by various symptoms.
A congenital abnormality of the cerebral hemisphere characterized by an excessive number of small gyri (convolutions) on the surface of the brain.
Hypoplasia of the cerebellum that is associated with inherited metabolic disorders and neurodegenerative disorders. Signs and symptoms include mental and developmental delays, walking and balance difficulties, floppy muscle tone, and seizures.
Colloid cysts of the third ventricle are benign tumors that may lie dormant and be found incidentally at autopsy or on CT or MRI examination. By contrast, in some cases they may cause severe, acute obstruction to the flow of cerebrospinal fluid, leading to coma and death. More commonly, they present as recurrent headaches, ataxia, nausea and vomiting, depression, memory loss, and emotional lability, all of which are associated with chronic hydrocephalus. Symptomatic colloid cysts are seen most commonly in middle life, but they also occur in childhood and old age (summary by Partington and Bookalil, 2004).
A congenital abnormality of the cerebral hemisphere chacterized by unusually thick gyrations (convolutions) of the cerebral cortex.
Brunelli et al. (1996) described schizencephaly as an extremely rare congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. The clefts are lined with gray matter and most commonly involve the parasylvian regions (Wolpert and Barnes, 1992). Large portions of the cerebral hemispheres may be absent and replaced by cerebrospinal fluid. Two types of schizencephaly have been described, depending on the size of the area involved and the separation of the cleft lips (Wolpert and Barnes, 1992). Type I schizencephaly consists of a fused cleft. This fused pial-ependymal seam forms a furrow in the developing brain, and is lined by polymicrogyric gray matter. In type II schizencephaly, there is a large defect, a holohemispheric cleft in the cerebral cortex filled with fluid and lined by polymicrogyric gray matter. The clinical manifestations depend on the severity of the lesion. Patients with type I are often almost normal; they may have seizures and spasticity. In type II abnormalities, there is usually mental retardation, seizures, hypotonia, spasticity, inability to walk or speak, and blindness. Schizencephaly may be part of the larger phenotypic spectrum of holoprosencephaly (HPE; see 236100).
A collection of heterotopic neuroglial tissue which is isolated from the cranial cavity, usually located in or around the nose. Complete excision is curative.
Gray matter heterotopia is a neurological disorder caused by clumps of grey matter being located in the wrong part of the brain. It is characterized as a type of cortical malformation. The neurons in heterotopia may appear to be normal, except for their mislocation; nuclear studies have shown glucose metabolism equal to that of normally positioned gray matter. The condition causes a variety of symptoms, but usually includes some degree of epilepsy or recurring seizures, and often affects the brain's ability to function on higher levels. Symptoms range from nonexistent to profound, in which case heterotopia can result in severe seizure disorder, loss of motor skills, and mental retardation.
A very rare, slow growing, usually asymptomatic hamartomatous lesion that arises from ectopic notochordal tissue. Morphologically it is characterized by the presence of typical physaliphorous cells in a myxoid background.
Rare vascular anomaly involving a communication between the intracranial and extracranial venous circulation via diploe, the central spongy layer of cranial bone. It is often characterized by dilated venous structures on the scalp due to abnormal drainage from the intracranial venous sinuses. Sinus pericranii can be congenital or traumatic in origin.
The severe form of a neural tube defect where the open neural tube appears as a flattened, plate-like mass of nervous tissue with no overlying membrane.
The Marcus Gunn phenomenon consists of unilateral congenital ptosis and rapid exaggerated elevation of the ptotic lid on moving of the lower jaw. Although it usually persists into adult life, the phenomenon is seen in its most marked forms in infancy when the rapid spasmodic movements of the lid are apparent during sucking and thus are noted soon after birth (Doco-Fenzy et al., 2006).
Abnormal development (dysgenesis) of the anterior segment of the eye globe. These structures are mainly of mesenchymal origin.
A congenital cataract in which opacity is limited to layers of the lens external to the nucleus (i.e., the perinuclear region), i.e., between the nuclear and cortical layers of the lens.
A congenital abnormality characterized by an abnormally small cornea. The horizontal corneal diameter is less than 10mm or less than 9mm in newborns. It is associated with an increased risk of glaucoma.
Axenfeld's anomaly is a bilateral disorder characterized by a prominent, anteriorly displaced Schwalbe's line (posterior embryotoxon) and peripheral iris strands which span the anterior chamber angle to attach to Schwalbe's line.
A developmental ocular anomaly in which the primary VITREOUS BODY and its surrounding hyaloid vasculature failed to regress. It is usually unilateral and characterized by CATARACT; MICROPHTHALMOS (small eyeballs), and retrolenticular fibrovascular tissue. (from Yanoff: Ophthalmology, 2nd ed.)
The abnormal formation of the eyelid that is present at the time of birth.
The drooping of the upper or lower eyelid that is present at the time of birth.
A finding in which the eye appears open at birth, either due to the congenital absence of eyelids or incomplete fusion of the eyelid.
The presence of more than the normal number of eyelids.
Absence of the inner ear due to a developmental defect.
Variably shaped, cartilage-containing tissue anterior to the external auditory meatus.
Small indentation anterior to the insertion of the ear.
The presence of an extra auricle on one or both sides of the head.
Anterior and inferior folding of the upper portion of the ear that obliterates triangular fossa and scapha.
A facial appearance characteristic of a fetus or neonate due to oligohydramnios experienced in the womb, comprising ocular hypertelorism, low-set ears, receding chin, and flattening of the nose.
An abnormality of the neck. [HPO:probinson]
A congenital branchial sinus is a remnant of the embryonic branchial arches and their intervening clefts and pouches that has failed to regress completely. Sinuses typically have their external orifice inferior to the ramus of the mandible. They may traverse the parotid gland, and run in close vicinity to the facial nerve in the external auditory canal.
An accessory spleen is a round, iso-echogenic, homogenic and smooth structure and is seen as a normal variant mostly on the medial contour of the spleen, near the hilus or around the lower pole. This has no pathogenic relevance.
An abnormal (non-anatomic) location of the spleen.
Joining of the spleen and a gonad during embryological development.
A left-right reversal (or ""mirror reflection"") of the anatomical location of the major thoracic and abdominal organs.
A congenital condition in which there is complete right-to-left reversal of the position of the thoracic organs.
Pregnancy loss with visible gestational sac or yolk sac or both but no visible embryo on ultrasonogram.
Cyclopia is a congenital abnormality in which there is only one eye. That eye is centrally placed in the area normally occupied by the root of the nose.
Congenital absence of the spinal cord and brain
A congenital malformation characterized by the union or approximation of the ears in front of the neck, often accompanied by the absence or defective development of the lower jaw.
A congenital abnormality characterized by a malformation of the head. The eyes are hypoteleric and the nose may be absent or misshapen (small, flattened, single nostril) and defective.
A congenital abnormality characterized by the presence of holoprosencephaly, a proboscis, the absence of a nose and microphthalmic, close-set eyes.
Congenital protrusion of the abdominal or thoracic viscera, usually with a defect of the sternum and ribs as well as of the abdominal walls.
A severe form of twin-twin transfusion syndrome that occurs in monochorionic pregnancies. The normal twin (pump twin) supplies the blood flow to its sibling that lacks heart or brain or both (acardiac/acephalic twin). Untreated, it may lead to the demise of the pump twin in some cases.
Epignathus is a teratoma originating from the upper jaw, usually connected with the sphenoid bone or hard palate.
A variant placenta in which the chorionic tissue is partitioned into two distinct discs, without consistent relationship to umbilical cord insertion.
Morbidly adherent placenta in which the chorionic villi invade into the myometrium.
Morbidly adherent placenta in which the chorionic villi invade through the myometrium.
A variant placenta in which the chorionic tissue is partitioned into more than two distinct discs, without consistent relationship to umbilical cord insertion.
A placenta characterized by fetal membranes that are folded along all or part of the disc perimeter. The amnion may or may not be included in the folded tissue.
A placenta characterized by fetal membranes which extend smoothly off the disc edge, and a subamnionic fibrin ring on all or part of the disc perimeter that delimits the greatest extent of the chorionic surface vessels.
Abnormality of the amniotic fluid, which is the fluid contained in the amniotic sac surrounding the developing fetus.
An abnormality of the umbilical cord, which is the cord connecting the developing embryo or fetus to the placenta.
An umbilical cord at term that is less than 35 cm in length.
Insertion of the umbilical cord within 2 cm from the placental edge.
Insertion of the umbilical cord into the chorio-amniotic membranes of the placenta.
A folding of the umbilical cord in the form of a knot.
A situation in utero, when there is increased pressure on the umbilical cord, which constricts blood supply to the fetus.
Hypersensitivity in form of an adverse immune reaction against cow milk protein.
A rare hereditary myopathic degeneration of both gastrointestinal and urinary tracts that causes chronic intestinal pseudo-obstruction. It usually presents after the first decade of life with megaduodenum, megacystis and symptoms such as abdominal distension and/or pain, vomiting, constipation, diarrhea, dysphagia, and/or urinary tract infections.
Paroxysms of irritability, fussing or crying that starts and stops without obvious cause in an infant up to four months of age without failure to thrive. Episodes last three or more hours per day for at least three days per week for at least on week.
Localized collection of pus in the tissues that enclose the root of a tooth and is associated with the presence of a sinus tract.
A non-neoplastic nodular lesion that arises from the gingiva.
Long-term inflammation of the gingiva surrounding the crown of a tooth, usually of an incompletely erupted tooth.
Chronic periodontitis, formerly called adult periodontitis, is the most frequently occurring form of periodontitis and is characterized by slowly progressing alveolar bone destruction and attachment loss. Although chronic periodontitis is most prevalent in adults and has a slow progression, it can occur in children and adolescents and may have periods of rapid progression (Armitage, 1999).
A bony protrusion present on the midline of the hard palate.
A benign lesion that involves the salivary glands, usually the parotid gland. It affects females more often than males and it may be a manifestation of autoimmune diseases such as Sjogren syndrome. There is an increased incidence of benign lymphoepithelial lesions in HIV-positive patients. It is characterized by the presence of a marked lymphocytic infiltrate and epi-myoepithelial islands in the affected salivary gland. Patients usually present with firm and painless swelling of the affected salivary gland. There is an increased risk for development of lymphoma.
A viral disease caused by at least two distinct species (serotypes) in the VESICULOVIRUS genus: VESICULAR STOMATITIS INDIANA VIRUS and VESICULAR STOMATITIS NEW JERSEY VIRUS. It is characterized by vesicular eruptions on the ORAL MUCOSA in cattle, horses, pigs, and other animals. In humans, vesicular stomatitis causes an acute influenza-like illness.
A velvety red but not ulcerated lesion of the oral mucosa. The texture may be roughened or normal, and the lesion is neither raised nor depressed.
A lobular hemangioma arising from the oral mucosa.
Inflammed tongue with hyperplastic (enlarged) fungiform papillae that is said to resemble a strawberry or raspberry.
Posterior displacement of the TONGUE toward the PHARYNX. It is often a feature in syndromes such as in PIERRE ROBIN SYNDROME and DOWN SYNDROME and associated with AIRWAY OBSTRUCTION during sleep (OBSTRUCTIVE SLEEP APNEAS).
Difficulty in swallowing due to an abnormality in the mouth or throat.
Difficulty in swallowing due to an abnormality in the esophagus.
A thin membrane that is present in the esophageal lumen. It is composed of mucosa and submucosa and it may be associated with Plummer-Vinson syndrome.
An abnormal connection between a bronchus and the esophagus.
A rare condition that usually affects the middle-to-distal esophagus in middle-aged and elderly people. There is usually a history of tobacco smoking or alcohol intake. Dysphagia is the presenting symptom. Morphologically, the lesions are well-demarcated and are characterized by epithelial hyperplasia, thickened basal layer, prominent granular cell layer, and hyperorthokeratosis. In a minority of patients this condition is associated with adjacent high-grade squamous dysplasia and/or squamous cell carcinoma.
A intraepithelial neoplasia (dysplasia) that arises in either the native gastric mucosa or in metaplastic gastric epithelium. It has a flat, polypoid or slightly depressed growth pattern. It is graded as low grade (mild dysplasia) or high grade (moderate dysplasia and carcinoma in situ). (WHO, 2000)
Infiltration of eosinophils in the stomach mucosa, that is diagnosed by an upper endoscopy and microscopy that shows more than 20 eosinophils per high-power field in association with peripheral eosinophilia and the absence of secondary cause of eosinophilia. [orcid.org/0000-0001-5208-3432, PMID:23904840]
A morphologic finding indicating the replacement of part of the gastric mucosal epithelium with intestinal-type epithelium. Using immunohistochemical staining, gastric intestinal metaplasia is classified as complete or incomplete. Complete intestinal metaplasia is defined by the decreased expression of gastric mucins and expression of the intestinal mucin MUC2. Incomplete intestinal metaplasia is defined by the co-expression of both gastric mucins and MUC2.
A rupture in the duodenal wall due to traumatic or pathologic processes.
An abnormal communication between the duodenum and another organ or cavity.
A chronic inflammatory disease of the large intestine (colon, cecum and rectum).
A non-neoplastic polypoid lesion in the colon. It may arise in a background of inflammatory bowel disease or colitis. It is characterized by the presence of a distorted epithelium, inflammation, and fibrosis.
A clot that obstructs blood flow in a mesenteric vein (the superior and the inferior mesenteric vein drain blood from the small and large intestine).
Inflammation of the colon that is characterized by eosinic infiltration.
Complete obstruction of the intestine due to the presence in the lumen of blocking material, such as tumor, fecalith, gallstone, or foreign body
Fibrosis of the wall of a segment of the intestine that leads to intestinal lumen narrowing.
A narrowing of a segment of colon whereby bowel continuity is maintained.
A circumscribed inflammatory and necrotic erosive lesion in the mucosa surface of the colon.
Interposition of a portion of the colon (e.g., SIGMOID COLON) between the liver and the diaphragm. It is associated with abdominal pain, vomiting, constipation, anorexia and volvulus. Chilaiditi anomaly refers to asymptomatic interposition.
Inflammation of a congenital diverticulum of the lower intestine.
Inflammation of the cecum, usually accompanied by neutropenia.
An acute necrotizing inflammation of the CECUM occurring in neutropenic patients.
Watery voluminous diarrhea resulting from an imbalance between ion and water secretion and absorption.
Infection of perianal region of skin following abrasion, which is named for the occurrence in horsemen
A non-neoplastic or neoplastic polypoid lesion that arises from the anus. Representative examples include the fibroepithelial polyp and squamous papilloma.
Bleeding originating from the rectal wall and discharged from the anus.
Congenital secretory chloride diarrhea is an autosomal recessive form of severe chronic diarrhea characterized by excretion of large amounts of watery stool containing high levels of chloride, resulting in dehydration, hypokalemia, and metabolic alkalosis. The electrolyte disorder resembles the renal disorder Bartter syndrome (see 607364), except that chloride diarrhea is not associated with calcium level abnormalities (summary by Choi et al., 2009). Genetic Heterogeneity of Diarrhea Other forms of diarrhea include DIAR2 (251850), caused by mutation in the MYO5B gene (606540) on 18q21; DIAR3 (270420), caused by mutation in the SPINT2 gene (605124) on 19q13; DIAR4 (610370), caused by mutation in the NEUROG3 gene (604882) on 10q21; DIAR5 (613217), caused by mutation in the EPCAM gene (185535) on 2p21; DIAR6 (614616), caused by mutation in the GUCY2C gene (601330) on 12p12; DIAR7 (615863) caused by mutation in the DGAT1 gene (604900) on 8q24; DIAR8 (616868), caused by mutation in the SLC9A3 gene (182307) on 5p15; DIAR9 (618168), caused by mutation in the WNT2B gene (601968) on 1p13; and DIAR10 (618183), caused by mutation in the PLVAP gene (607647) on 19p13.
An abdominal hernia that occurs at a site of weakness in the abdominal wall resulting from an incompletely-healed surgical wound.
A HIATAL HERNIA in which the STOMACH herniation is located alongside the ESOPHAGUS and the ESOPHAGOGASTRIC JUNCTION is in its normal position below the DIAPHRAGM.
The presence of an abscess of the peritoneum.
An abscess that is located in any part of the tissue composing the mesentery, and that generally arises from an infection in an adjacent area of the intestine.
This entity represents the fibrotic stage of MESENTERY inflammation.
A rare, benign process that affects the peritoneal cavity and is characterized by the formation of multiple small nodules that are composed of well differentiated smooth muscle. It usually affects adults in their late reproductive years. Most patients are asymptomatic. The tumor nodules may regress spontaneously.
A non-neoplastic or neoplastic disorder that affects the liver, bile ducts, and gallbladder. Representative examples of non-neoplastic disorders include hepatitis, cirrhosis, cholangitis, and cholecystitis. Representative examples of neoplastic disorders include hepatocellular adenoma, hepatocellular carcinoma, and cholangiocarcinoma.
Cryptogenic cirrhosis is a condition that impairs liver function. People with this condition develop irreversible liver disease caused by scarring of the liver (cirrhosis), typically in mid- to late adulthood.The liver is a part of the digestive system that helps break down food, store energy, and remove waste products, including toxins. Minor damage to the liver can be repaired by the body. However, severe or long-term damage can lead to the replacement of normal liver tissue with scar tissue.In the early stages of cryptogenic cirrhosis, people often have no symptoms because the liver has enough normal tissue to function. Signs and symptoms become apparent as more of the liver is replaced by scar tissue. Affected individuals can experience fatigue, weakness, loss of appetite, weight loss, nausea, swelling (edema), enlarged blood vessels, and yellowing of the skin and whites of the eyes (jaundice).People with cryptogenic cirrhosis may develop high blood pressure in the vein that supplies blood to the liver (portal hypertension). Cryptogenic cirrhosis can lead to type 2 diabetes, although the mechanism is unclear. Some people with cryptogenic cirrhosis develop cancer of the liver (hepatocellular cancer).
A type of cirrhosis characterized by the presence of small regenerative nodules.
Proliferative changes of the bile ducts.
Single or multiple areas of PUS due to bacterial infection within the hepatic parenchyma. It can be caused by a variety of BACTERIA, local or disseminated from infections elsewhere such as in APPENDICITIS; CHOLECYSTITIS; PERITONITIS; and after LIVER TRANSPLANTATION.
A form of amyloidosis that affects the liver.
Inflammation of the GALLBLADDER wall in the absence of GALLSTONES.
Acute inflammation of the gallbladder in the absence of gallstones
An acute or chronic inflammation of the gallbladder associated with the presence of gallstones.
Complication of CHOLELITHIASIS characterized by OBSTRUCTIVE JAUNDICE; abdominal pain, and fever.
Cholangitis that is both sudden in onset and of a relatively short duration.
Cholangitis that is persistent and long-standing.
Cholangitis characterized by the presence of numerous polymorphonuclear cells around and within the wall as well as within the lumen of the ducts. This may involve ducts of any size and is occasionally associated with abscess formation (cholangitic abscess).
Narrowing or stricture of the bile duct.
A severe form of acute INFLAMMATION of the PANCREAS characterized by one or more areas of NECROSIS in the pancreas with varying degree of involvement of the surrounding tissues or organ systems. Massive pancreatic necrosis may lead to DIABETES MELLITUS, and malabsorption.
A necrotic process affecting the pancreas.
A malabsorption condition resulting from greater than 10% reduction in the secretion of pancreatic digestive enzymes (LIPASE; PROTEASES; and AMYLASE) by the EXOCRINE PANCREAS into the DUODENUM. This condition is often associated with CYSTIC FIBROSIS and with chronic PANCREATITIS.
An increased concentration of proteins in the blood.
A decreased concentration of potassium(1+) in the urine.
Sudden onset of impairment in ventilation such that the removal of carbon dioxide by the respiratory system is less than the production of carbon dioxide in the tissues, leading to an elevation of the partial pressure of carbon dioxide (PaCO2) above the normal limits (more than 45 mm Hg) with an accompanying acidemia (pH less than 7.35).
Longstanding impairment in ventilation such that the partial pressure of carbon dioxide (PaCO2) is elevated above the upper limit of the reference range (more than 45 mm Hg), with a normal or near-normal pH secondary to renal compensation and an elevated serum bicarbonate levels (more than30 mEq/L).
Neonatal hemochromatosis (NH) is characterized by hepatic failure in the newborn period and heavy iron staining in the liver. In addition, there is marked siderosis of extrahepatic tissues, including the heart and pancreas (Driscoll et al., 1988). Whitington (2007) postulated that some cases of neonatal hemochromatosis result from maternal alloimmunity directed at the fetal liver, and therefore do not represent an inherited mendelian disorder. Other causes may result from metabolic disease or perinatal infection. In particular, he commented that the disorder is not related to the family of inherited liver diseases that fall under the classification of hereditary hemochromatosis (see, e.g., 235200). Whitington (2007) proposed the term 'congenital alloimmune hepatitis.' In the past, the disorder has loosely been labeled 'neonatal hepatitis' and 'giant cell hepatitis,' which are pathologic findings in the liver representing a common response to a variety of insults, including cholestatic disorders and infection, among others (Fawaz et al., 1975; Knisely et al., 1987; Kelly et al., 2001).
Juvenile hemochromatosis is characterized by onset of severe iron overload occurring typically in the first to third decades of life. Males and females are equally affected. Prominent clinical features include hypogonadotropic hypogonadism, cardiomyopathy, arthropathy, and liver fibrosis or cirrhosis. Hepatocellular cancer has not been reported. The main cause of death is cardiac disease. If juvenile hemochromatosis is detected early enough and if blood is removed regularly through the process of phlebotomy to achieve iron depletion, morbidity and mortality are greatly reduced.
African iron overload is a distinct iron-loading disorder prevalent in Africa. Formerly termed Bantu siderosis, the disorder results from a predisposition to iron loading that is exacerbated by excessive intake of dietary iron. It is particularly a problem among Africans who drink a traditional beer brewed in non-galvanized steel drums. Although the disorder was once attributed to dietary excess alone, serious iron overload does not develop in all beer drinkers, and not all patients with iron overload consume excessive amounts of the beer (summary by Andrews, 1999).
Accumulation of iron in internal organs that results from repeated blood transfusions.
A reduced concentration of copper in the blood.
An abnormally decreased phosphate concentration in the urine.
An increased excretion of phosphates in the urine.
Virtually complete deficiency of HPRT residual activity is associated with the Lesch-Nyhan syndrome (LNS; 300322), whereas partial deficiency (at least 8%) is associated with the Kelley-Seegmiller syndrome. LNS is characterized by abnormal metabolic and neurologic manifestations. In contrast, Kelley-Seegmiller syndrome is usually associated only with the clinical manifestations of excessive purine production. Renal stones, uric acid nephropathy, and renal obstruction are often the presenting symptoms of Kelley-Seegmiller syndrome, but rarely of LNS. After puberty, the hyperuricemia in Kelley-Seegmiller syndrome may cause gout (summary by Zoref-Shani et al., 2000).
Xanthinuria, which was first described by Dent and Philpot (1954), is characterized by excretion of large amounts of xanthine in the urine and a tendency to form xanthine stones. Uric acid is strikingly diminished in serum and urine. Two clinically similar but distinct forms of xanthinuria are recognized. In type I there is an isolated deficiency of xanthine dehydrogenase, and in type II (XAN2; 603592) there is a dual deficiency of xanthine dehydrogenase and aldehyde oxidase (603592). Type I patients can metabolize allopurinol, whereas type II patients cannot (Simmonds et al., 1995). Xanthinuria also occurs in molybdenum cofactor deficiency (252150). Type II xanthinuria is caused by mutation in the MOCOS gene (613274), which encodes the enzyme that sulfurates the molybdenum cofactor for XDH and AOX1 (602841).
Molybdenum cofactor deficiency (MOCOD) is a rare autosomal recessive metabolic disorder characterized by onset in infancy of poor feeding, intractable seizures, and severe psychomotor retardation. Characteristic biochemical abnormalities include decreased serum uric acid and increased urine sulfite levels due to the combined enzymatic deficiency of xanthine dehydrogenase (XDH; 607633) and sulfite oxidase (SUOX; 606887), both of which use molybdenum as a cofactor. Most affected individuals die in early childhood (summary by Reiss, 2000; Reiss et al., 2011). Genetic Heterogeneity of Molybdenum Cofactor Deficiency See also MOCOD, complementation group B (MOCODB; 252160), caused by mutation in the MOCS2 gene (602708) on chromosome 5q11; and MOCOD, complementation group C (MOCODC; 615501), caused by mutation in the GPHN gene (603930) on chromosome 14q24.
Adenine phosphoribosyltransferase (APRT) deficiency is characterized by excessive production of 2,8-dihydroxyadenine (DHA), which is excreted in the urine, where it is poorly soluble and leads to kidney stone formation and chronic kidney disease (CKD). Kidney stones, the most common clinical manifestation of APRT deficiency, can occur at any age; in at least 50% of affected individuals symptoms do not occur until adulthood. In a significant number of individuals, intratubular and interstitial precipitation of DHA crystals can result in kidney failure (i.e., DHA crystal nephropathy).
An autosomal recessive deficiency of the purine salvage enzyme adenosine deaminase which results in Severe Combined Immunodeficiency Disease (SCID). The most common form of SCID, accounting for about 50% of autosomal recessive cases. The first disease for which gene therapy was applied.
Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disorder characterized mainly by decreased T-cell function. Some patients also have neurologic impairment (review by Aust et al., 1992).
Adenylosuccinase deficiency is an autosomal recessive inborn error of metabolism caused by an enzymatic defect in de novo purine synthesis (DNPS) pathway. ADSL deficiency leads to the accumulation of toxic intermediates, including succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICAr) in body fluids. There are 3 major phenotypic forms of the disorder that correlate with different values of the S-Ado and SAICAr concentration ratios (S-Ado/SAICAr) in the cerebrospinal fluid. These include the most severe fatal neonatal encephalopathy (S-Ado/SAICAr ratio less than 1); childhood form (type I) with severe psychomotor retardation (S-Ado/SAICAr ratio close to 1), and a milder form (type II) with psychomotor retardation or hypotonia (S-Ado/SAICAr ratio greater than 2) (summary by Baresova et al., 2012).
Orotic aciduria is a rare autosomal recessive disorder characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Bailey (2009) stated that only 2 cases of orotic aciduria without megaloblastic anemia (OAWA) had been reported.
Phosphorylase kinase (PhK) deficiency causing glycogen storage disease type IX (GSD IX) results from deficiency of the enzyme phosphorylase b kinase, which has a major regulatory role in the breakdown of glycogen. The two types of PhK deficiency are liver PhK deficiency (characterized by early childhood onset of hepatomegaly and growth restriction, and often, but not always, fasting ketosis and hypoglycemia) and muscle PhK deficiency, which is considerably rarer (characterized by any of the following: exercise intolerance, myalgia, muscle cramps, myoglobinuria, and progressive muscle weakness). While symptoms and biochemical abnormalities of liver PhK deficiency were thought to improve with age, it is becoming evident that patients need to be monitored for long-term complications such as liver fibrosis and cirrhosis.
Phosphoglycerate mutase deficiency is a disorder that primarily affects muscles used for movement (skeletal muscles). Beginning in childhood or adolescence, affected individuals experience muscle aches or cramping following strenuous physical activity. Some people with this condition also have recurrent episodes of myoglobinuria. Myoglobinuria occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin, which is processed by the kidneys and released in the urine. If untreated, myoglobinuria can lead to kidney failure.In some cases of phosphoglycerate mutase deficiency, microscopic tube-shaped structures called tubular aggregates are seen in muscle fibers. It is unclear how tubular aggregates are associated with the signs and symptoms of the disorder.
Infants with Duarte variant galactosemia who are on breast milk or a lactose-containing formula are typically, but not always, asymptomatic. Abnormalities, such as jaundice, which may be seen in some infants, resolve rapidly when the baby is switched to a low-galactose formula. Many health care professionals believe that Duarte variant galactosemia does not result in clinical disease either with or without dietary intervention; however, there are also reports to the contrary and no adequately powered study either confirming or refuting this assumption has been reported. Because available data about the neurodevelopmental outcomes of children with Duarte variant galactosemia are conflicting, further studies are warranted to determine what long-term outcomes are and whether the dietary intake of galactose in the first year of life influences outcome. Premature ovarian insufficiency has not been reported for girls or women with Duarte variant galactosemia.
Galactokinase deficiency is an autosomal recessive disorder that causes cataract formation in children not maintained on a lactose-free diet. Cataract formation is the result of osmotic phenomena caused by the accumulation of galactitol in the lens (Asada et al., 1999).
Elevated concentration of galactose in the urine.
Essential fructosuria is a benign, asymptomatic defect of intermediary metabolism characterized by the intermittent appearance of fructose in the urine (summary by Bonthron et al., 1994).
Essential pentosuria is an inborn error of metabolism in which 1 to 4 gm of the pentose L-xylulose is excreted in the urine each day. It is a benign condition that occurs principally in individuals of Ashkenazi Jewish descent (summary by Hiatt, 2001).
Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of the liver peroxisomal enzyme alanine:glyoxylate-aminotransferase (AGT), which catalyzes the conversion of glyoxylate to glycine. When AGT activity is absent, glyoxylate is converted to oxalate, which forms insoluble calcium oxalate crystals that accumulate in the kidney and other organs. Individuals with PH1 are at risk for recurrent nephrolithiasis (deposition of calcium oxalate in the renal pelvis / urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), or end-stage renal disease (ESRD). Age at onset of symptoms ranges from infancy to the sixth decade. Approximately 10% of affected individuals present in infancy or early childhood with nephrocalcinosis, with or without nephrolithiasis, and failure to thrive related to renal failure. The majority of individuals with PH1 present in childhood or early adolescence, usually with symptomatic nephrolithiasis and normal or reduced kidney function. The remainder of affected individuals present in adulthood with recurrent renal stones and a mild-to-moderate reduction in kidney function. The natural history of untreated PH1 is one of progressive decline in renal function as a result of calcium oxalate deposits in kidney tissue and complications of nephrolithiasis (e.g., obstruction and infection) with eventual progression to oxalosis (widespread tissue deposition of calcium oxalate) and death from ESRD and/or complications of oxalosis.
Primary hyperoxaluria type 2 (PH2), caused by deficiency of the enzyme glyoxylate reductase/hydroxypyruvate reductase (GR/HPR), is characterized by recurrent nephrolithiasis (deposition of calcium oxalate in the renal pelvis/urinary tract), nephrocalcinosis (deposition of calcium oxalate in the renal parenchyma), and end-stage renal disease (ESRD). After ESRD, oxalosis (widespread tissue deposition of calcium oxalate) usually develops. Symptom onset is typically in childhood.
Excessive urinary oxalate excretion resulting from increased absorption of oxalate.
Congenital lactase deficiency is a severe gastrointestinal disorder characterized by watery diarrhea in infants fed with breast milk or other lactose-containing formulas.
In humans, the activities of lactase and most of the other digestive hydrolases are maximal at birth. The majority of the world's human population experiences a decline in production of the digestive enzyme lactase-phlorizin hydrolase during maturation, with the age of onset ranging from the toddler years to young adulthood. Due to the reduced lactase level, lactose present in dairy products cannot be digested in the small intestine and instead is fermented by bacteria in the distal ileum and colon. The fermentative products result in symptoms of diarrhea, gas bloat, flatulence, and abdominal pain. However, in a minority of adults, high levels of lactase activity persist in adulthood. Lactase persistence is a heritable autosomal dominant condition that results in a sustained ability to digest the milk sugar lactose throughout adulthood (Olds and Sibley, 2003).
Glucose/galactose malabsorption (GGM) is a rare autosomal recessive disorder caused by a defect in glucose and galactose transport across the intestinal brush border. Patients with GGM present with neonatal onset of severe life-threatening watery diarrhea and dehydration. If diagnosed and treated properly, patients can fully recover and show normal growth and development (summary by Xin and Wang, 2011).
Trehalose is a disaccharide found in mushrooms, algae, and insect hemolymph; mushrooms and products containing baker's yeast are thus the only sources of trehalose in the human diet. The high concentration of trehalose in cryptobiotic plants is responsible for their remarkable ability to go through cycles of desiccation and rehydration without injury. This led to interest by the food industry in the addition of trehalose to foodstuffs to improve the longevity and quality of dried food. However, ingestion of a disaccharide in an individual who cannot digest it results in osmotic diarrhea, abdominal pain, and increased rectal flatulence (summary by Murray et al., 2000). Isolated trehalose intolerance due to deficiency of trehalase (TREH; 275360) is probably rare in adult white Americans (Welsh et al., 1978), but has been estimated at 8% in Greenlanders (Gudmand-Hoyer et al., 1988).
Methemoglobinemia due to NADH-cytochrome b5 reductase deficiency is an autosomal recessive disorder characterized clinically by decreased oxygen carrying capacity of the blood, with resultant cyanosis and hypoxia (review by Percy and Lappin, 2008). There are 2 types of methemoglobin reductase deficiency. In type I, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type II, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes, and all body tissues. Type II methemoglobinemia is associated with mental deficiency and other neurologic symptoms. The neurologic symptoms may be related to the major role played by the cytochrome b5 system in the desaturation of fatty acids (Vives-Corrons et al., 1978; Kaplan et al., 1979).
A very rare, autosomal recessive inherited disorder caused by deficiency of the enzyme phosphoenolpyruvate carboxykinase, which is involved in gluconeogenesis. It presents with hypoglycemia, failure to thrive, metabolic acidosis, muscle weakness, and hepatomegaly.
inherited diseases characterized by the presence of abnormally low levels of lipoproteins in the blood.
Aspartylglucosaminuria is a severe autosomal recessive lysosomal storage disorder that involves the central nervous system and causes skeletal abnormalities as well as connective tissue lesions. The most characteristic feature is progressive mental retardation. The disorder is caused by deficient activity of the lysosomal enzyme glycosylasparaginase, which results in body fluid and tissue accumulation of a series of glycoasparagines, i.e., glycoconjugates with an aspartylglucosamine moiety at the reducing end. AGU belongs to the group of disorders commonly referred to as the Finnish disease heritage (summary by Mononen et al., 1993 and Arvio and Arvio, 2002).
An autosomal recessive inherited lysosomal storage disease characterized by excessive intracellular accumulation and urinary excretion of sialic acid associated with neuraminidase deficiency.
Galactosialidosis is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase (611458) and neuraminidase (608272), secondary to a defect in protective protein/cathepsin A (PPCA). All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and rare occurrence of neurologic signs. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival. The majority of reported patients belong to the juvenile/adult group and are mainly of Japanese origin (summary by d'Azzo et al., 2001).
Leigh syndrome (or subacute necrotizing encephalomyelopathy) is characterized by decompensation (often with elevated lactate levels in blood and/or CSF) during an intercurrent illness. It is typically associated with psychomotor retardation or regression, often followed by transient or prolonged stabilization or even improvement, but inevitably resulting in eventual progressive neurologic decline, typically occurring in stepwise decrements. Neurologic manifestations include hypotonia, spasticity, movement disorders (including chorea), cerebellar ataxia, and peripheral neuropathy. Extraneurologic manifestations may include hypertrophic cardiomyopathy, hypertrichosis, anemia, renal tubulopathy, liver involvement, ptosis, and muscle weakness. Onset is typically between ages three and 12 months; about 50% of affected individuals die by age three years, most often as a result of respiratory or cardiac failure. Later onset (including in adulthood) and long-term survival may occasionally occur.
Chanarin-Dorfman syndrome is a condition in which fats (lipids) are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides, and these fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. People with this condition also have dry, scaly skin (ichthyosis), which is usually present at birth. Additional features of this condition include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts), difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness (myopathy), involuntary movement of the eyes (nystagmus), and mild intellectual disability.The signs and symptoms vary greatly among individuals with Chanarin-Dorfman syndrome. Some people may have ichthyosis only, while others may have problems affecting many areas of the body.
Niemann-Pick disease is a condition that affects many body systems. It has a wide range of symptoms that vary in severity. Niemann-Pick disease is divided into four main types: type A, type B, type C1, and type C2. These types are classified on the basis of genetic cause and the signs and symptoms of the condition.Infants with Niemann-Pick disease type A usually develop an enlarged liver and spleen (hepatosplenomegaly) by age 3 months and fail to gain weight and grow at the expected rate (failure to thrive). The affected children develop normally until around age 1 year when they experience a progressive loss of mental abilities and movement (psychomotor regression). Children with Niemann-Pick disease type A also develop widespread lung damage (interstitial lung disease) that can cause recurrent lung infections and eventually lead to respiratory failure. All affected children have an eye abnormality called a cherry-red spot, which can be identified with an eye examination. Children with Niemann-Pick disease type A generally do not survive past early childhood.Niemann-Pick disease type B usually presents in mid-childhood. The signs and symptoms of this type are similar to type A, but not as severe. People with Niemann-Pick disease type B often have hepatosplenomegaly, recurrent lung infections, and a low number of platelets in the blood (thrombocytopenia). They also have short stature and slowed mineralization of bone (delayed bone age). About one-third of affected individuals have the cherry-red spot eye abnormality or neurological impairment. People with Niemann-Pick disease type B usually survive into adulthood.The signs and symptoms of Niemann-Pick disease types C1 and C2 are very similar; these types differ only in their genetic cause. Niemann-Pick disease types C1 and C2 usually become apparent in childhood, although signs and symptoms can develop at any time. People with these types usually develop difficulty coordinating movements (ataxia), an inability to move the eyes vertically (vertical supranuclear gaze palsy), poor muscle tone (dystonia), severe liver disease, and interstitial lung disease. Individuals with Niemann-Pick disease types C1 and C2 have problems with speech and swallowing that worsen over time, eventually interfering with feeding. Affected individuals often experience progressive decline in intellectual function and about one-third have seizures. People with these types may survive into adulthood.
The spectrum of ASAH1-related disorders ranges from Farber disease (FD) to spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). Classic FD is characterized by onset in the first weeks of life of painful, progressive deformity of the major joints; palpable subcutaneous nodules of joints and mechanical pressure points; and a hoarse cry resulting from granulomas of the larynx and epiglottis. Life expectancy is usually less than two years. In the other less common types of FD, onset, severity, and primary manifestations vary. SMA-PME is characterized by early-childhood-onset progressive lower motor neuron disease manifest typically between ages three and seven years as proximal lower-extremity weakness, followed by progressive myoclonic and atonic seizures, tremulousness/tremor, and sensorineural hearing loss. Myoclonic epilepsy typically begins in late childhood after the onset of weakness and can include jerking of the upper limbs, action myoclonus, myoclonic status, and eyelid myoclonus. Other findings include generalized tremor, and cognitive decline. The time from disease onset to death from respiratory complications is usually five to 15 years.
Metachromatic leukodystrophy is an inherited disorder characterized by the accumulation of fats called sulfatides in cells. This accumulation especially affects cells in the nervous system that produce myelin, the substance that insulates and protects nerves. Nerve cells covered by myelin make up a tissue called white matter. Sulfatide accumulation in myelin-producing cells causes progressive destruction of white matter (leukodystrophy) throughout the nervous system, including in the brain and spinal cord (the central nervous system) and the nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound (the peripheral nervous system).In people with metachromatic leukodystrophy, white matter damage causes progressive deterioration of intellectual functions and motor skills, such as the ability to walk. Affected individuals also develop loss of sensation in the extremities (peripheral neuropathy), incontinence, seizures, paralysis, an inability to speak, blindness, and hearing loss. Eventually they lose awareness of their surroundings and become unresponsive. While neurological problems are the primary feature of metachromatic leukodystrophy, effects of sulfatide accumulation on other organs and tissues have been reported, most often involving the gallbladder.The most common form of metachromatic leukodystrophy, affecting about 50 to 60 percent of all individuals with this disorder, is called the late infantile form. This form of the disorder usually appears in the second year of life. Affected children lose any speech they have developed, become weak, and develop problems with walking (gait disturbance). As the disorder worsens, muscle tone generally first decreases, and then increases to the point of rigidity. Individuals with the late infantile form of metachromatic leukodystrophy typically do not survive past childhood.In 20 to 30 percent of individuals with metachromatic leukodystrophy, onset occurs between the age of 4 and adolescence. In this juvenile form, the first signs of the disorder may be behavioral problems and increasing difficulty with schoolwork. Progression of the disorder is slower than in the late infantile form, and affected individuals may survive for about 20 years after diagnosis.The adult form of metachromatic leukodystrophy affects approximately 15 to 20 percent of individuals with the disorder. In this form, the first symptoms appear during the teenage years or later. Often behavioral problems such as alcoholism, drug abuse, or difficulties at school or work are the first symptoms to appear. The affected individual may experience psychiatric symptoms such as delusions or hallucinations. People with the adult form of metachromatic leukodystrophy may survive for 20 to 30 years after diagnosis. During this time there may be some periods of relative stability and other periods of more rapid decline.Metachromatic leukodystrophy gets its name from the way cells with an accumulation of sulfatides appear when viewed under a microscope. The sulfatides form granules that are described as metachromatic, which means they pick up color differently than surrounding cellular material when stained for examination.
Initial symptoms of multiple sulfatase deficiency (MSD) can develop from infancy through early childhood, and presentation is widely variable. Some individuals display the multisystemic features characteristic of mucopolysaccharidosis disorders (e.g., developmental regression, organomegaly, skeletal deformities) while other individuals present primarily with neurologic regression (associated with leukodystrophy). Based on age of onset, rate of progression, and disease severity, several different clinical subtypes of MSD have been described: Neonatal MSD is the most severe with presentation in the prenatal period or at birth with rapid progression and death occurring within the first two years of life. Infantile MSD is the most common variant and may be characterized as attenuated (slower clinical course with cognitive disability and neurodegeneration identified in the 2nd year of life) or severe (loss of the majority of developmental milestones by age 5 years). Juvenile MSD is the rarest subtype with later onset of symptoms and subacute clinical presentation. Many of the features found in MSD are progressive, including neurologic deterioration, heart disease, hearing loss, and airway compromise.
A group of recessively inherited diseases characterized by the intralysosomal accumulation of G(M2) GANGLIOSIDE in the neuronal cells. Subtypes include mutations of enzymes in the BETA-N-ACETYLHEXOSAMINIDASES system or G(M2) ACTIVATOR PROTEIN leading to disruption of normal degradation of GANGLIOSIDES, a subclass of ACIDIC GLYCOSPHINGOLIPIDS.
The GM2-gangliosidoses are a group of disorders caused by excessive accumulation of ganglioside GM2 and related glycolipids in the lysosomes, mainly of neuronal cells. GM2-gangliosidosis AB variant is characterized by normal hexosaminidase A (HEXA; 606869) and hexosaminidase B (HEXB; 606873) but the inability to form a functional GM2 activator complex. The clinical and biochemical phenotype of the AB variant is very similar to that of classic Tay-Sachs disease (see 272800) (Gravel et al., 2001).
CLN1 disease is an inherited disorder that primarily affects the nervous system. Individuals with this condition have normal development in infancy, but typically by 18 months they become increasingly irritable and begin to lose previously acquired skills (developmental regression). In affected children, brain cells die over time, leading to an overall loss of brain tissue (brain atrophy) and an unusually small head (microcephaly). Children with CLN1 disease have decreased muscle tone (hypotonia), intellectual and motor disability, and rarely are able to speak or walk. Some affected children develop repetitive hand movements. By age 2, individuals with this condition often have muscle twitches (myoclonus), recurrent seizures (epilepsy), and vision loss. Some affected children develop frequent respiratory infections. As the condition worsens, children have severe feeding difficulties that often require a feeding tube. Children with CLN1 disease usually do not survive past childhood.Some people with CLN1 disease do not develop symptoms until later in childhood or in adulthood. As with younger affected children, older individuals develop a decline in intellectual function, myoclonus, epilepsy, and vision loss. In these individuals, life expectancy depends on when signs and symptoms of CLN1 disease develop and their severity; affected individuals may survive only into adolescence or through adulthood. Adults with CLN1 disease may also have movement disorders, including impaired muscle coordination (ataxia) or a pattern of movement abnormalities known as parkinsonism.CLN1 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation ""CLN,"" meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype.
condition in which there is a deviation or interruption in the processing of steroids in the body: synthesis, absorption, transport, storage, and utilization.
17 alpha(a)-hydroxylase/17,20-lyase deficiency is a condition that affects the function of certain hormone-producing glands called the gonads (ovaries in females and testes in males) and the adrenal glands. The gonads direct sexual development before birth and during puberty and are important for reproduction. The adrenal glands, which are located on top of the kidneys, regulate the production of certain hormones, including those that control salt levels in the body. People with 17a-hydroxylase/17,20-lyase deficiency have an imbalance of many of the hormones that are made in these glands. 17a-hydroxylase/17,20-lyase deficiency is one of a group of disorders, known as congenital adrenal hyperplasias, that impair hormone production and disrupt sexual development and maturation.Hormone imbalances lead to the characteristic signs and symptoms of 17a-hydroxylase/17,20-lyase deficiency, which include high blood pressure (hypertension), low levels of potassium in the blood (hypokalemia), and abnormal sexual development. The severity of the features varies. Two forms of the condition are recognized: complete 17a-hydroxylase/17,20-lyase deficiency, which is more severe, and partial 17a-hydroxylase/17,20-lyase deficiency, which is typically less so.Males and females are affected by disruptions to sexual development differently. Females (who have two X chromosomes) with 17a-hydroxylase/17,20-lyase deficiency are born with normal external female genitalia; however, the internal reproductive organs, including the uterus and ovaries, may be underdeveloped. Women with complete 17a-hydroxylase/17,20-lyase deficiency do not develop secondary sex characteristics, such as breasts and pubic hair, and do not menstruate (amenorrhea). Women with partial 17a-hydroxylase/17,20-lyase deficiency may develop some secondary sex characteristics; menstruation is typically irregular or absent. Either form of the disorder results in an inability to conceive a baby (infertility).In affected individuals who are chromosomally male (having an X and a Y chromosome), problems with sexual development lead to abnormalities of the external genitalia. The most severely affected are born with characteristically female external genitalia and are generally raised as females. However, because they do not have female internal reproductive organs, these individuals have amenorrhea and do not develop female secondary sex characteristics. These individuals have testes, but they are abnormally located in the abdomen (undescended). Sometimes, complete 17a-hydroxylase/17,20-lyase deficiency leads to external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Males with partial 17a-hydroxylase/17,20-lyase deficiency usually have abnormal male genitalia, such as a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), or a scrotum divided into two lobes (bifid scrotum). Males with either complete or partial 17a-hydroxylase/17,20-lyase deficiency are also infertile.
Less than necessary amount of the enzyme steroid 21-monooxygenase; which is necessary to synthesize cortisol.
Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency is an autosomal recessive disorder of corticosteroid biosynthesis resulting in androgen excess, virilization, and hypertension. The defect causes decreased synthesis of cortisol and corticosterone in the zona fasciculata of the adrenal gland, resulting in accumulation of the precursors 11-deoxycortisol and 11-deoxycorticosterone; the latter is a potent salt-retaining mineralocorticoid that leads to arterial hypertension (White et al., 1991). CAH due to 11-beta-hydroxylase deficiency accounts for approximately 5 to 8% of all CAH cases; approximately 90% of cases are caused by 21-hydroxylase deficiency (201910) (White et al., 1991).
HSD17B3 deficiency is an autosomal recessive disorder that manifests, in males, as undermasculinization characterized by hypoplastic-to-normal internal genitalia (epididymis, vas deferens, seminal vesicles, and ejaculatory ducts) but female external genitalia and the absence of a prostate. This phenotype is caused by inadequate testicular synthesis of testosterone, which, in turn, results in insufficient formation of dihydrotestosterone in the anlage of the external genitalia and prostate during fetal development. At the expected time of puberty, there is a marked increase in plasma leuteinizing hormone and, consequently, in testicular secretion of androstenedione. Hence, a diagnostic hallmark of this disorder is a decreased plasma testosterone-to-androstenedione ratio. Significant amounts of the circulating androstenedione are, however, converted to testosterone, in peripheral tissues, thereby causing virilization (summary by Lindqvist et al., 2001).
Pseudovaginal perineoscrotal hypospadias is a form of male pseudohermaphroditism in which 46,XY males show ambiguous genitalia at birth, including perineal hypospadias and a blind perineal pouch, and develop masculinization at puberty. The name of the disorder stems from the finding of a blind-ending perineal opening resembling a vagina and a severely hypospadiac penis with the urethra opening onto the perineum.
Individuals with androgen insensitivity have a 46,XY karyotype and testes that produce age-appropriate androgen levels but have undermasculinized external genitalia due to defects in androgen action. The phenotype in PAIS varies depending on residual androgen receptor function, ranging from severe undermasculinization presenting as female-like external genitalia to male-appearing genitalia. The typical presentation comprises micropenis, severe hypospadias, and bifid scrotum with or without cryptorchidism (summary by Mongan et al., 2015).
Abnormally high level of unconjugated bilirubin in the blood.
Abnormally high level of conjugated bilirubin in the blood.
Progressive familial intrahepatic cholestasis (PFIC) is a disorder that causes progressive liver disease, which typically leads to liver failure. In people with PFIC, liver cells are less able to secrete a digestive fluid called bile. The buildup of bile in liver cells causes liver disease in affected individuals.Signs and symptoms of PFIC typically begin in infancy and are related to bile buildup and liver disease. Specifically, affected individuals experience severe itching, yellowing of the skin and whites of the eyes (jaundice), failure to gain weight and grow at the expected rate (failure to thrive), high blood pressure in the vein that supplies blood to the liver (portal hypertension), and an enlarged liver and spleen (hepatosplenomegaly).There are three known types of PFIC: PFIC1, PFIC2, and PFIC3. The types are also sometimes described as shortages of particular proteins needed for normal liver function. Each type has a different genetic cause.In addition to signs and symptoms related to liver disease, people with PFIC1 may have short stature, deafness, diarrhea, inflammation of the pancreas (pancreatitis), and low levels of fat-soluble vitamins (vitamins A, D, E, and K) in the blood. Affected individuals typically develop liver failure before adulthood.The signs and symptoms of PFIC2 are typically related to liver disease only; however, these signs and symptoms tend to be more severe than those experienced by people with PFIC1. People with PFIC2 often develop liver failure within the first few years of life. Additionally, affected individuals are at increased risk of developing a type of liver cancer called hepatocellular carcinoma.Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can occur in childhood or adulthood in people with PFIC3.
A rare genetic syndrome which occurs primarily among individuals of Norwegian descent with an autosomal recessive pattern of inheritance. It is caused, in some cases, by the inheritance of a mutation of the LSC1 gene on chromosome 15. Clinical signs include lymphedema of the lower extremities and cholestasis. The clinical course includes giant-cell hepatitis and progression to cirrhosis.
Familial porphyria cutanea tarda (F-PCT) is characterized by: skin findings including blistering over the dorsal aspects of the hands and other sun-exposed areas of skin, skin friability after minor trauma, facial hypertrichosis and hyperpigmentation, and severe thickening of affected skin areas (pseudoscleroderma); and an increased risk for hepatocellular carcinoma (HCC).
ALAD porphyria is a rare autosomal recessive disorder that has been reported and confirmed by genetic analysis in only 5 patients (Jaffe and Stith, 2007).
Ehlers-Danlos syndrome, type I belongs to the classical type Ehlers-Danlos syndrome. It results most often from mutations in either the COL5A1 gene or the COL5A2 gene.
Ehlers-Danlos syndrome, type II belongs to the classical type Ehlers-Danlos syndrome. It results most often from mutations in either the COL5A1 gene or the COL5A2 gene.
Hypermobile Ehlers-Danlos syndrome (hEDS) is generally considered the least severe type of EDS, although significant complications, primarily musculoskeletal, can and do occur. The skin is often soft and may be mildly hyperextensible. Subluxations and dislocations are common; they may occur spontaneously or with minimal trauma and can be acutely painful. Degenerative joint disease is common. Chronic pain, distinct from that associated with acute dislocations, is a serious complication of the condition and can be both physically and psychologically disabling. Easy bruising, functional bowel disorders, and cardiovascular autonomic dysfunction are common. Aortic root dilation, when present, is typically of a mild degree with no increased risk of dissection in the absence of significant dilation. Psychological dysfunction, psychosocial impairment, and emotional problems are common.
Vascular Ehlers-Danlos syndrome (vEDS) is characterized by arterial, intestinal, and/or uterine fragility; thin, translucent skin; easy bruising; characteristic facial appearance (thin vermilion of the lips, micrognathia, narrow nose, prominent eyes); and an aged appearance to the extremities, particularly the hands. Vascular dissection or rupture, gastrointestinal perforation, or organ rupture are the presenting signs in most adults with vEDS. Arterial rupture may be preceded by aneurysm, arteriovenous fistulae, or dissection but also may occur spontaneously. The majority (60%) of individuals with vEDS who are diagnosed before age 18 years are identified because of a positive family history. Neonates may present with clubfoot, hip dislocation, limb deficiency, and/or amniotic bands. Approximately half of children tested for vEDS in the absence of a positive family history present with a major complication at an average age of 11 years. Four minor diagnostic features – distal joint hypermobility, easy bruising, thin skin, and clubfeet – are most often present in those children ascertained without a major complication.
PLOD1-related kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is an autosomal recessive generalized connective tissue disorder characterized by hypotonia, early-onset kyphoscoliosis, and generalized joint hypermobility in association with skin fragility and ocular abnormality. Intelligence is normal. Life span may be normal, but affected individuals are at risk for rupture of medium-sized arteries. Adults with severe kyphoscoliosis are at risk for complications from restrictive lung disease, recurrent pneumonia, and cardiac failure.
Brittle cornea syndrome (BCS) is characterized by blue sclerae, corneal rupture after minor trauma, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobility of the joints (Al-Hussain et al., 2004). It is classified as a form of Ehlers-Danlos syndrome (Malfait et al., 2017). Genetic Heterogeneity of Brittle Cornea Syndrome Brittle cornea syndrome-2 (BCS2; 614170) is caused by mutation in the PRDM5 gene (614161) on chromosome 4q27.
Ehlers-Danlos syndrome, type VII includes the arthrochalasia type (types VIIA and VIIB) Ehlers-Danlos syndrome, and the dermatosparaxis type (type VIIC) Ehlers-Danlos syndrome. The arthrochalasia type Ehlers-Danlos syndrome is caused by mutations in the COL1A1 gene or the COL1A2 gene. The dermatosparaxis type Ehlers-Danlos syndrome is caused by mutations in the ADAMTS2 gene.
Cutis laxa is a disorder of connective tissue, which is the tissue that forms the body's supportive framework. Connective tissue provides structure and strength to the muscles, joints, organs, and skin.The term ""cutis laxa"" is Latin for loose or lax skin, and this condition is characterized by skin that is sagging and not stretchy (inelastic). The skin often hangs in loose folds, causing the face and other parts of the body to have a droopy appearance. Extremely wrinkled skin may be particularly noticeable on the neck and in the armpits and groin.Cutis laxa can also affect connective tissue in other parts of the body, including the heart, blood vessels, joints, intestines, and lungs. The disorder can cause heart problems and abnormal narrowing, bulging, or tearing of critical arteries. Affected individuals may have soft out-pouchings in the lower abdomen (inguinal hernia) or around the belly button (umbilical hernia). Pouches called diverticula can also develop in the walls of certain organs, such as the bladder and intestines. During childhood, some people with cutis laxa develop a lung disease called emphysema, which can make it difficult to breathe. Depending on which organs and tissues are affected, the signs and symptoms of cutis laxa can range from mild to life-threatening.Researchers have described several different forms of cutis laxa. The forms are often distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. In general, the autosomal recessive forms of cutis laxa tend to be more severe than the autosomal dominant forms. In addition to the features described above, some people with autosomal recessive cutis laxa have delayed development, intellectual disability, seizures, and problems with movement that can worsen over time.The X-linked form of cutis laxa is often called occipital horn syndrome. This form of the disorder is considered a mild type of Menkes syndrome, which is a condition that affects copper levels in the body. In addition to sagging and inelastic skin, occipital horn syndrome is characterized by wedge-shaped calcium deposits in a bone at the base of the skull (the occipital bone), coarse hair, and loose joints.
Occipital horn syndrome is a rare connective tissue disorder characterized by hyperelastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities, and multiple skeletal abnormalities. The disorder is sometimes accompanied by mild neurologic impairment, and bony abnormalities of the occiput are a common feature, giving rise to the name (summary by Das et al., 1995).
De Barsy syndrome, or autosomal recessive cutis laxa type III (ARCL3), is characterized by cutis laxa, a progeria-like appearance, and ophthalmologic abnormalities (summary by Kivuva et al., 2008). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see 219100. Genetic Heterogeneity of de Barsy Syndrome Also see ARCL3B (614438), caused by mutation in the PYCR1 gene (179035) on chromosome 17q25.
ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), spans a phenotypic spectrum that includes Debré-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end. Affected individuals have furrowing of the skin of the whole body that improves with time. They may have other evidence of a generalized connective disorder, including enlarged anterior fontanelle in infancy, congenital dislocation of the hips, inguinal hernias, and high myopia. In most (not all) affected individuals, cortical and cerebellar malformations are present and are associated with severe developmental delays, seizures, and neurologic regression.
A severe form of osteogenesis imperfecta. It is characterized by bone deformities, multiple fractures, underdeveloped lungs, and often death during or after birth due to respiratory abnormalities.
A nonproliferative disorder of the PLASMA CELL characterized by excessive production and misfolding of IMMUNOGLOBULIN LIGHT CHAINS that form insoluble amyloid fibrils (see AMYLOID DEPOSITS) in various tissues. Clinical features include LIVER FAILURE; MULTIPLE MYELOMA; NEPHROTIC SYNDROME; RESTRICTIVE CARDIOMYOPATHY, and neuropathies.
A form of amyloidosis that affects the kidney.
Muckle-Wells syndrome (MWS) is characterized by episodic skin rash, arthralgias, and fever associated with late-onset sensorineural deafness and renal amyloidosis (Dode et al., 2002). See also familial cold-induced autoinflammatory syndrome-1 (FCAS1, CAPS1; 120100), an allelic disorder with overlapping clinical features.
A familial disorder marked by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES.
Primary localized cutaneous amyloidosis is characterized clinically by pruritus and skin scratching and histologically by the finding of deposits of amyloid staining on keratinous debris in the papillary dermis (summary by Tanaka et al., 2009). Genetic Heterogeneity of Primary Localized Cutaneous Amyloidosis Primary localized cutaneous amyloidosis-2 (PLCA2; 613955) is caused by heterozygous mutation in the IL31RA gene (609510) on chromosome 5q11. Primary localized cutaneous amyloidosis-3 (PLCA3; 617920) is caused by mutation in the GPNMB gene (604368) on chromosome 7p15.
A form of amyloidosis that affects the conjunctiva.
Extracellular deposition in cardiac tissue of a proteinaceous material that, when stained with Congo red, demonstrates apple-green birefringence under polarized light and that has a distinct color when stained with sulfated Alcian blue. Viewed with electron microscopy, the amyloid deposits are seen to be composed of a beta-sheet fibrillar material. These nonbranching fibrils have a diameter of 7.5 to 10 nm and are the result of protein misfolding.
Paget disease of bone-5 is an autosomal recessive, juvenile-onset form of Paget disease, a disorder of the skeleton resulting from abnormal bone resorption and formation. Clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness. There is phenotypic variability, with some patients presenting in infancy, while others present later in childhood (summary by Naot et al., 2014). For discussion of genetic heterogeneity of Paget disease of bone, see 167250.
NR0B1-related adrenal hypoplasia congenita includes both X-linked adrenal hypoplasia congenita (X-linked AHC) and Xp21 deletion (previously called complex glycerol kinase deficiency). X-linked AHC is characterized by primary adrenal insufficiency and/or hypogonadotropic hypogonadism (HH). Adrenal insufficiency is acute infantile onset (average age 3 weeks) in approximately 60% of affected males and childhood onset (ages 1-9 years) in approximately 40%. HH typically manifests in a male with adrenal insufficiency as delayed puberty (i.e., onset age >14 years) and less commonly as arrested puberty at about Tanner Stage 3. Rarely, X-linked AHC manifests initially in early adulthood as delayed-onset adrenal insufficiency, partial HH, and/or infertility. Heterozygous females very occasionally have manifestations of adrenal insufficiency or hypogonadotropic hypogonadism. Xp21 deletion includes deletion of NR0B1 (causing X-linked AHC) and GK (causing glycerol kinase deficiency), and in some cases deletion of DMD (causing Duchenne muscular dystrophy). Developmental delay has been reported in males with Xp21 deletion when the deletion extends proximally to include DMD or when larger deletions extend distally to include IL1RAPL1 and DMD.
Acatalasemia, also known as acatalasia, is a metabolic disorder characterized by a total or near total loss of catalase activity in erythrocytes. About half of cases originate from ulcerating oral gangrenes, and these cases are referred to as having Takahara disease. Half-normal levels of catalase in heterozygotes is referred to as hypocatalasemia or hypocatalasia (Ogata, 1991).
Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated or restrictive cardiomyopathy, the insulin resistance syndrome, and multiple organ failure. Wide clinical variability is observed among affected individuals, even within the same family. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus usually starting between birth and age 15 months. Many individuals lose all perception of light by the end of the second decade, but a minority retain the ability to read large print into the third decade. Children usually have normal birth weight but develop truncal obesity during their first year. Progressive sensorineural hearing loss presents in the first decade in as many as 70% of individuals. Hearing loss may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance is typically accompanied by the skin changes of acanthosis nigricans, and proceeds to type 2 diabetes in the majority by the third decade. Nearly all demonstrate associated dyslipidemia. Other endocrine abnormalities can include hypothyroidism, hypogonadotropic hypogonadism in boys, and polycystic ovaries in girls. More than 60% of individuals with Alström syndrome develop cardiac failure as a result of dilated or restrictive cardiomyopathy. About 50% of individuals have delay in early developmental milestones; intelligence is normal. Liver involvement includes elevation of transaminases, steatosis, hepatosplenomegaly, and steatohepatitis. Portal hypertension and cirrhosis can lead to hepatic encephalopathy and life-threatening esophageal varices. Pulmonary dysfunction and severe renal disease may also develop. End-stage renal disease (ESRD) can occur as early as the late teens.
A type of renal tubular acidosis characterized by a failure of the proximal tubular cells to reabsorb bicarbonate, leading to urinary bicarbonate wasting and subsequent acidemia.
A hereditary, heterogeneous disorder of electrolyte metabolism that is characterized by renal resistance to aldosterone action, resulting in salt wasting, hypotension, hyperkalemia, and metabolic acidosis.
An autosomal dominant inherited non-dystrophic myotonia caused by mutations of the SCN4A gene, resulting in sodium muscle channelopathy. Currently, it is considered a variant of hyperkalemic periodic paralysis. Patients with normokalemic periodic paralysis do not have any change in their potassium levels during weakness, but become weak when they ingest potassium.
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a progressive renal disorder characterized by excessive urinary Ca(2+) and Mg(2+) excretion. There is progressive loss of kidney function, and in about 50% of cases, the need for renal replacement therapy arises as early as the second decade of life (summary by Muller et al., 2006). Amelogenesis imperfecta may also be present in some patients (Bardet et al., 2016). A similar disorder with renal magnesium wasting, renal failure, and nephrocalcinosis (HOMG5; 248190) is caused by mutations in another tight-junction gene, CLDN19 (610036), and is distinguished by the association of severe ocular involvement. For a discussion of phenotypic and genetic heterogeneity of familial hypomagnesemia, see HOMG1 (602014).
Gitelman syndrome is an autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. It is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most patients have onset of symptoms as adults, but some can present in childhood. Clinical features include transient periods of muscle weakness and tetany, abdominal pains, and chondrocalcinosis (summary by Glaudemans et al., 2012). Gitelman syndrome is sometimes referred to as a mild variant of classic Bartter syndrome (607364). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
A condition of not having consistently high levels of phenylalanine in the blood but of experiencing temporary hyperphenylalaninemia following ingestion of large quantities of phenylalanine (for instance, following an oral loading test with phenylalanine).
Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency. This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain.Infants with tetrahydrobiopterin deficiency appear normal at birth, but medical problems ranging from mild to severe become apparent over time. Signs and symptoms of this condition can include intellectual disability, progressive problems with development, movement disorders, difficulty swallowing, seizures, behavioral problems, and an inability to control body temperature.
The phenotypic spectrum of sepiapterin reductase deficiency (SRD), which ranges from significant motor and cognitive deficits to only minimal findings, has not been completely elucidated. Clinical features in the majority of affected individuals include motor and speech delay, axial hypotonia, dystonia, weakness, and oculogyric crises; symptoms show diurnal fluctuation and sleep benefit. Other common features include parkinsonian signs (tremor, bradykinesia, masked facies, rigidity), limb hypertonia, hyperreflexia, intellectual disability, psychiatric and/or behavioral abnormalities, autonomic dysfunction, and sleep disturbances (hypersomnolence, difficulty initiating or maintaining sleep, and drowsiness). Most affected individuals have nonspecific features in infancy including developmental delays and axial hypotonia; other features develop over time.
An increased concentration of tryptophan in the urine.
A group of disorders which have in common elevations of tyrosine in the blood and urine secondary to an enzyme deficiency. Type I tyrosinemia features episodic weakness, self-mutilation, hepatic necrosis, renal tubular injury, and seizures and is caused by a deficiency of the enzyme fumarylacetoacetase. Type II tyrosinemia features INTELLECTUAL DISABILITY, painful corneal ulcers, and keratoses of the palms and plantar surfaces and is caused by a deficiency of the enzyme TYROSINE TRANSAMINASE. Type III tyrosinemia features INTELLECTUAL DISABILITY and is caused by a deficiency of the enzyme 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE. (Menkes, Textbook of Child Neurology, 5th ed, pp42-3)
Tyrosinemia type II is an autosomal recessive disorder characterized by keratitis, painful palmoplantar hyperkeratosis, mental retardation, and elevated serum tyrosine levels. The disorder is caused by deficiency of hepatic tyrosine aminotransferase (Natt et al., 1992).
Untreated tyrosinemia type I usually presents either in young infants with severe liver involvement or later in the first year with liver dysfunction and renal tubular dysfunction associated with growth failure and rickets. Untreated children may have repeated, often unrecognized, neurologic crises lasting one to seven days that can include change in mental status, abdominal pain, peripheral neuropathy, and/or respiratory failure requiring mechanical ventilation. Death in the untreated child usually occurs before age ten years, typically from liver failure, neurologic crisis, or hepatocellular carcinoma. Combined treatment with nitisinone and a low-tyrosine diet has resulted in a greater than 90% survival rate, normal growth, improved liver function, prevention of cirrhosis, correction of renal tubular acidosis, and improvement in secondary rickets.
A group of tyrosine related oculocutaneous albinism (OCA1) that includes OCA1A, OCA1B, type 1 minimal pigment oculocutaneous albinism (OCA1-MP) and type 1 temperature sensitive oculocutaneous albinism (OCA1-TS). The phenotypic spectrum seen in OCA1 is variable. Pigmentation present in the skin, hair and eyes can range from little or none to pigmentation only to the peripheries. Findings of nystagmus, photophobia and reduced visual acuity are often present. The disease is caused by a mutation in the TYR gene located on chromosome 11q14.3 encoding tyrosinase. Mutations in OCA1A and OCA1B lead to a total or partial loss of the catalytic activity of tyrosinase while those in OCA1-MP and OCA1-TS lead to minimal activity or temperature sensitive tyrosinase proteins. The different forms of OCA1 are all transmitted autosomal recessively.
Oculocutaneous albinism type 2 (OCA2) is characterized by hypopigmentation of the skin and hair and the characteristic ocular changes found in all types of albinism, including nystagmus; reduced iris pigment with iris translucency; reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination; foveal hypoplasia associated with reduction in visual acuity; and misrouting of the optic nerve fiber radiations at the chiasm, associated with strabismus, reduced stereoscopic vision, and altered visual evoked potentials (VEP). Individuals with OCA2 are usually recognized within the first three to six months of life because of the ocular features of visual inattention, nystagmus, and strabismus. Vision is stable to slowly improving after early childhood until mid- to late teens, and no major change or loss of established visual acuity occurs related to the albinism. The amount of cutaneous pigmentation in OCA2 ranges from minimal to near-normal compared to others of the same ethnic and family backgrounds. Newborns with OCA2 almost always have lightly pigmented hair, brows, and lashes, with color ranging from light yellow to blond to brown. Hair color may darken with age but does not vary substantially from adolescence to adulthood. Brown OCA, initially identified in Africans and African Americans with light brown hair and skin, is part of the spectrum of OCA2.
Aland Island eye disease (AIED) is an X-linked recessive retinal disease characterized by fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, protan color vision defect (303900), progressive myopia, and defective dark adaptation. Although AIED has been referred to as a form of albinism, there is no misrouting of the optic nerves, which excludes it from the formal diagnosis of classic albinism (King et al., 2001).
An increased concentration of urocanic acid in the urine.
5-Oxoprolinuria can be caused by genetic defects in either of 2 enzymes involved in the gamma-glutamyl cycle of glutathione metabolism: glutathione synthetase (GSS; 601002) or 5-oxoprolinase (OPLAH; 614243). GSS deficiency (266130) is best characterized as an inborn error of glutathione metabolism, but there is debate as to whether OPLAH deficiency represents a disorder or simply a biochemical condition with no adverse clinical effects because patients lack a consistent clinical picture apart from 5-oxoprolinuria (summary by Calpena et al., 2013).
An increased concentration of proline in the blood.
Phang et al. (2001) noted that prospective studies of HPI probands identified through newborn screening as well as reports of several families have suggested that it is a metabolic disorder not clearly associated with clinical manifestations. Phang et al. (2001) concluded that HPI is a relatively benign condition in most individuals under most circumstances. However, other reports have suggested that some patients have a severe phenotype with neurologic manifestations, including epilepsy and mental retardation (Jacquet et al., 2003). Genetic Heterogeneity of Hyperprolinemia See also hyperprolinemia type II (HYRPRO2; 239510), which is caused by mutation in the gene encoding pyrroline-5-carboxylate dehydrogenase (P5CDH, ALDH4A1; 606811) on chromosome 1p36.
Hydroxyproline is an imino acid normally present in human plasma. It is derived primarily from endogenous collagen turnover and the breakdown of dietary collagen. The finding of elevated (5- to 10-fold increase from the normal of less than 50 micromoles) serum hydroxyproline is thought to be an inherited defect in the catabolism of hydroxyproline.
Prolidase deficiency is characterized by skin lesions (typically severe, chronic, recalcitrant, and painful skin ulcers of the lower extremities and telangiectasias of the face and hands), recurrent infections (particularly of the skin and respiratory tract), dysmorphic facial features, variable intellectual disability, and hepatomegaly with elevated liver enzymes and splenomegaly. Anemia, thrombocytopenia, hypergammaglobulinemia, and hypocomplementemia are common. An association between systemic lupus erythematosus (SLE) and prolidase deficiency has been described.
An increased concentration of proline in the urine.
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is characterized by variable clinical presentation and age of onset. Neonatal onset (~12% of affected individuals). Infants are normal for the first 24-48 hours followed by onset of symptoms related to hyperammonemia (poor feeding, vomiting, lethargy, low temperature, rapid breathing). Information on long-term outcome is limited. Infancy, childhood, and adult presentation (~88%). Affected individuals may present with: Chronic neurocognitive deficits (including developmental delay, ataxia, spasticity, learning disabilities, cognitive deficits and/or unexplained seizures); Acute encephalopathy secondary to hyperammonemic crisis precipitated by a variety of factors; and Chronic liver dysfunction (unexplained elevation of liver transaminases with or without mild coagulopathy, with or without mild hyperammonemia and protein intolerance). Neurologic findings and cognitive abilities can continue to deteriorate despite early metabolic control that prevents hyperammonemia.
Ornithine transcarbamylase (OTC) deficiency can occur as a severe neonatal-onset disease in males (but rarely in females) and as a post-neonatal-onset (partial deficiency) disease in males and females. Males with severe neonatal-onset OTC deficiency are typically normal at birth but become symptomatic from hyperammonemia on day two to three of life and are usually catastrophically ill by the time they come to medical attention. After successful treatment of neonatal hyperammonemic coma these infants can easily become hyperammonemic again despite appropriate treatment; they typically require liver transplant by age six months to improve quality of life. Males and heterozygous females with post-neonatal-onset (partial) OTC deficiency can present from infancy to later childhood, adolescence, or adulthood. No matter how mild the disease, a hyperammonemic crisis can be precipitated by stressors and become a life-threatening event at any age and in any situation in life. For all individuals with OTC deficiency, typical neuropsychological complications include developmental delay, learning disabilities, intellectual disability, attention deficit hyperactivity disorder (ADHD), and executive function deficits.
N-acetylglutamate synthase deficiency is an autosomal recessive disorder of the urea cycle. The clinical and biochemical features of the disorder are indistinguishable from carbamoyl phosphate synthase I deficiency (237300), since the CPS1 enzyme (608307) has an absolute requirement for NAGS (Caldovic et al., 2007).
Deficiency of argininosuccinate lyase (ASL), the enzyme that cleaves argininosuccinic acid to produce arginine and fumarate in the fourth step of the urea cycle, may present as a severe neonatal-onset form and a late-onset form: The severe neonatal-onset form is characterized by hyperammonemia within the first few days after birth that can manifest as increasing lethargy, somnolence, refusal to feed, vomiting, tachypnea, and respiratory alkalosis. Absence of treatment leads to worsening lethargy, seizures, coma, and even death. In contrast, the manifestations of late-onset form range from episodic hyperammonemia triggered by acute infection or stress to cognitive impairment, behavioral abnormalities, and/or learning disabilities in the absence of any documented episodes of hyperammonemia. Manifestations of ASL deficiency (ASLD) that appear to be unrelated to the severity or duration of hyperammonemic episodes: Neurocognitive deficiencies (attention-deficit/hyperactivity disorder, developmental delay, seizures, and learning disability). Liver disease (hepatitis, cirrhosis). Trichorrhexis nodosa (coarse brittle hair that breaks easily). Systemic hypertension.
Arginase deficiency in untreated individuals is characterized by episodic hyperammonemia of variable degree that is infrequently severe enough to be life threatening or to cause death. Most commonly, birth and early childhood are normal. Untreated individuals have slowing of linear growth at age one to three years, followed by development of spasticity, plateauing of cognitive development, and subsequent loss of developmental milestones. If untreated, arginase deficiency usually progresses to severe spasticity, loss of ambulation, complete loss of bowel and bladder control, and severe intellectual disability. Seizures are common and are usually controlled easily.
An increased concentration of lysine in the blood.
Saccharopinuria, also known as hyperlysinemia type II, is an autosomal recessive metabolic condition with few, if any, clinical manifestations. Hyperlysinemia type II and hyperlysinemia type I (238700) both result from deficiency of the bifunctional enzyme AASS (605113) on chromosome 7q31. The AASS gene encodes lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase, which catalyze, respectively, the sequential conversion of lysine to saccharopine and saccharopine to alpha-aminoadipic semialdehyde and glutamate (summary by Tondo et al., 2013). In hyperlysinemia type I, both enzymatic functions of AASS are defective and patients have increased serum lysine and possibly increased saccharopine; in hyperlysinemia type II, most of the first enzymatic function is retained, and patients tend to have isolated saccharopine increase (Cox, 1985; Cox et al., 1985).
An elevated concentration of glycine in the blood.
Sarcosinemia is characterized by an increased concentration of sarcosine in plasma and an increased excretion of sarcosine in urine. Sarcosine (N-methylglycine) is enzymatically formed from dimethylglycine by dimethylglycine dehydrogenase (EC 1.5.99.2) and converted to glycine by sarcosine dehydrogenase (SARDH; 604455; EC 1.5.99.1). Some reports have associated sarcosinemia with mental retardation and neurologic problems, but the disorder is most likely benign and unrelated to significant clinical problems (summary by Scott, 2001).
Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine. It is also characterized by poor feeding, vomiting, lack of energy (lethargy), abnormal movements, and delayed development. If untreated, maple syrup urine disease can lead to seizures, coma, and death.Maple syrup urine disease is often classified by its pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which becomes apparent soon after birth. Variant forms of the disorder become apparent later in infancy or childhood and are typically milder, but they still lead to delayed development and other health problems if not treated.
An increased concentration of valine in the blood.
Isovaleric acidemia is an inborn error of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. It can present with severe neonatal ketoacidosis leading to death, but in milder cases recurrent episodes of ketoacidosis of varying degree occur later in infancy and childhood (summary by Vockley et al., 1991).
An increased concentration of leucine in the blood.
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to late-onset disease. Neonatal-onset PA, the most common form, is characterized by a healthy newborn with poor feeding and decreased arousal in the first few days of life, followed by progressive encephalopathy of unexplained origin. Without prompt diagnosis and management, this is followed by progressive encephalopathy manifesting as lethargy, seizures, or coma that can result in death. It is frequently accompanied by metabolic acidosis with anion gap, lactic acidosis, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. Individuals with late-onset PA may remain asymptomatic and suffer a metabolic crisis under catabolic stress (e.g., illness, surgery, fasting) or may experience a more insidious onset with the development of multiorgan complications including vomiting, protein intolerance, failure to thrive, hypotonia, developmental delays or regression, movement disorders, or cardiomyopathy. Isolated cardiomyopathy can be observed on rare occasion in the absence of clinical metabolic decompensation or neurocognitive deficits. Manifestations of neonatal and late-onset PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency, and chronic renal failure.
Holocarboxylase synthetase deficiency, a biotin-responsive multiple carboxylase deficiency (MCD), is characterized by metabolic acidosis, lethargy, hypotonia, convulsions, and dermatitis. Most patients present in the newborn or early infantile period, but some become symptomatic in the later infantile period (summary by Suzuki et al., 2005). Also see biotinidase deficiency (253260), another form of MCD with a later onset. Care must be taken to differentiate the inherited multiple carboxylase deficiencies from acquired biotin deficiencies, such as those that develop after excessive dietary intake of avidin, an egg-white glycoprotein that binds specifically and essentially irreversibly to biotin (Sweetman et al., 1981) or prolonged parenteral alimentation without supplemental biotin (Mock et al., 1981).
Isolated methylmalonic acidemia/aciduria, the topic of this GeneReview, is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut– enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. Onset of the manifestations of isolated methylmalonic acidemia/aciduria ranges from the neonatal period to adulthood. All phenotypes are characterized by periods of relative health and intermittent metabolic decompensation, usually associated with intercurrent infections and stress. In the neonatal period the disease can present with lethargy, vomiting, hypotonia, hypothermia, respiratory distress, severe ketoacidosis, hyperammonemia, neutropenia, and thrombocytopenia and can result in death within the first four weeks of life. In the infantile/non-B12-responsive phenotype, infants are normal at birth, but develop lethargy, vomiting, dehydration, failure to thrive, hepatomegaly, hypotonia, and encephalopathy within a few weeks to months of age. An intermediate B12-responsive phenotype can occasionally be observed in neonates, but is usually observed in the first months or years of life; affected children exhibit anorexia, failure to thrive, hypotonia, and developmental delay, and sometimes have protein aversion and/or vomiting and lethargy after protein intake. Atypical and ""benign""/adult methylmalonic acidemia phenotypes are associated with increased, albeit mild, urinary excretion of methylmalonate. Major secondary complications of methylmalonic acidemia include: intellectual impairment (variable); tubulointerstitial nephritis with progressive renal failure; ""metabolic stroke"" (acute and chronic basal ganglia injury) causing a disabling movement disorder with choreoathetosis, dystonia, and para/quadriparesis; pancreatitis; growth failure; functional immune impairment; and optic nerve atrophy.
An increased concentration of glutaric acid in the urine.
Glutaric acidemia I is an autosomal recessive metabolic disorder characterized by gliosis and neuronal loss in the basal ganglia and a progressive movement disorder that usually begins during the first year of life (Goodman et al., 1995). Hedlund et al. (2006) provided a detailed review of the clinical and biochemical aspects of glutaric acidemia type I.
Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I (GA1; 231670) in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids. GA II results from deficiency of any 1 of 3 molecules: the alpha (ETFA) and beta (ETFB) subunits of electron transfer flavoprotein, and electron transfer flavoprotein dehydrogenase (ETFDH). The clinical picture of GA II due to the different defects appears to be indistinguishable; each defect can lead to a range of mild or severe cases, depending presumably on the location and nature of the intragenic lesion, i.e., mutation, in each case (Goodman, 1993; Olsen et al., 2003). The heterogeneous clinical features of patients with MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in patients with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress (summary by Frerman and Goodman, 2001). Importantly, riboflavin treatment has been shown to ameliorate the symptoms and metabolic profiles in many MADD patients, particularly those with type III, the late-onset and mildest form (Liang et al., 2009).
3-methylcrotonyl-CoA carboxylase deficiency (also known as 3-MCC deficiency) is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have a shortage of an enzyme that helps break down proteins containing a particular building block (amino acid) called leucine.Infants with 3-MCC deficiency appear normal at birth but usually develop signs and symptoms in infancy or early childhood. The characteristic features of this condition, which can range from mild to life-threatening, include feeding difficulties, recurrent episodes of vomiting and diarrhea, excessive tiredness (lethargy), and weak muscle tone (hypotonia). If untreated, this disorder can lead to delayed development, seizures, and coma. Many of these complications can be prevented with early detection and lifelong management with a low-protein diet and appropriate supplements. Some people with gene mutations that cause 3-MCC deficiency never experience any signs or symptoms of the condition.The characteristic features of 3-MCC deficiency are similar to those of Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency is a rare autosomal recessive disorder with the cardinal manifestations of metabolic acidosis without ketonuria, hypoglycemia, and a characteristic pattern of elevated urinary organic acid metabolites, including 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels of 3-methylcrotonylglycine may be increased. Dicarboxylic aciduria, hepatomegaly, and hyperammonemia may also be observed. Presenting clinical signs include irritability, lethargy, coma, and vomiting (summary by Gibson et al., 1988).
Glutamate formiminotransferase deficiency is an autosomal recessive disorder and the second most common inborn error of folate metabolism. Features of a severe phenotype include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and mental retardation. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematologic abnormalities (summary by Hilton et al., 2003).
A rare autosomal dominant inherited metabolic disorder characterized by deficiency of the enzyme tetrahydrofolate-methyltransferase. It results in the abnormal metabolism of methylcobalamin. Signs and symptoms include mental retardation, megaloblastic anemia, hypotonia, epilepsy, and hepatosplenomegaly.
A rare disorder associated with mental retardation, spasticity, and early death.
An increased concentration of cystathionine in the blood.
Methionine adenosyltransferase deficiency is an inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some with the autosomal recessive form have have neurologic abnormalities (Mudd et al., 2003; Kim et al., 2016).
Tyrosinemia type III is an autosomal recessive disorder caused by a deficiency in the activity of 4-hydroxyphenylpyruvate dioxygenase (HPD) and is characterized by elevated levels of blood tyrosine and massive excretion of its derivatives into urine. Patients with this disorder have mild mental retardation and/or convulsions, with the absence of liver damage (summary by Tomoeda et al., 2000).
Abnormally reduced sulfite oxidase activity.
Cystinosis comprises three allelic phenotypes: Nephropathic cystinosis in untreated children is characterized by renal Fanconi syndrome, poor growth, hypophosphatemic/calcipenic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine in almost all cells, leading to cellular dysfunction with tissue and organ impairment. The typical untreated child has short stature, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these interventions, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized clinically only by photophobia resulting from corneal cystine crystal accumulation.
An increased concentration of alanine in the blood. [HPO:gcarletti, pmid:16902722, pmid:4696900]
Succinic semialdehyde dehydrogenase (SSADH) deficiency is characterized by infantile-onset hypotonia, developmental delay, cognitive impairment, expressive language deficit, and mild ataxia. Epilepsy is present in about half of affected individuals and is more common in adults. Hyperkinetic behavior, aggression, self-injurious behaviors, hallucinations, and sleep disturbances have been reported in nearly half of all affected individuals, more commonly in those who are older. Basal ganglia signs including choreoathetosis, dystonia, and myoclonus have been reported in a few individuals with earlier-onset, more severe disease. Involvement beyond the central nervous system has not been described. Individuals with SSADH deficiency typically have 4-hydroxybutyric aciduria present on urine organic acid analysis. Head MRI reveals T2 hyperintensities in multiple regions, involving the globus pallidi, cerebellar dentate nuclei, subthalamic nuclei, subcortical white matter, and brain stem, as well as cerebral and sometimes cerebellar atrophy. EEG findings include background slowing and spike discharges that are usually generalized.
A group of genetic disorders that result from the inability to produce or use an enzyme required to oxidize fatty acids, resulting in an inability to generate energy from fatty acid sources.
An increased concentration of histidine in the urine.
Lysinuric protein intolerance (LPI) typically presents after an infant is weaned from breast milk or formula; variable findings include recurrent vomiting and episodes of diarrhea, episodes of stupor and coma after a protein-rich meal, poor feeding, aversion to protein-rich food, failure to thrive, hepatosplenomegaly, and muscular hypotonia. Over time, findings include: poor growth, osteoporosis, involvement of the lungs (progressive interstitial changes, pulmonary alveolar proteinosis) and of the kidneys (progressive glomerular and proximal tubular disease), hematologic abnormalities (normochromic or hypochromic anemia, leukopenia, thrombocytopenia, erythroblastophagocytosis in the bone marrow aspirate), and a clinical presentation resembling the hemophagocytic lymphohistiocytosis/macrophagic activation syndrome. Hypercholesterolemia, hypertriglyceridemia, and acute pancreatitis can also be seen.
The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria (IG), a benign inborn error of amino acid transport, is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG; 138500) (summary by Broer et al., 2008). Iminoglycinuria may be more frequent in Ashkenazim than in others (Tancredi et al., 1970). Iminoglycinuria also occurs as part of the generalized amino aciduria of the Fanconi renotubular syndrome (134600).
Vitamin D3 (cholecalciferol), synthesized in the epidermis in response to UV radiation, and dietary vitamin D2 (ergocalciferol, synthesized in plants) are devoid of any biologic activity. Vitamin D hormonal activity is due primarily to the hydroxylated metabolite of vitamin D3, 1-alpha,25-dihydroxyvitamin D3 (calcitriol), the actions of which are mediated by the vitamin D receptor (VDR; 601769) (Koren, 2006; Liberman and Marx, 2001). In the liver, vitamin D 25-hydroxylase (CYP2R1; 608713) catalyzes the initial hydroxylation of vitamin D at carbon 25; in the kidney, 1-alpha-hydroxylase (CYP27B1; 609506) catalyzes the hydroxylation and metabolic activation of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3. The active metabolite 1,25(OH)2D3 binds and activates the nuclear vitamin D receptor, with subsequent regulation of physiologic events such as calcium homeostasis and cellular differentiation and proliferation (Takeyama et al., 1997). Disorders of vitamin D metabolism or action lead to defective bone mineralization and clinical features including intestinal malabsorption of calcium, hypocalcemia, secondary hyperparathyroidism, increased renal clearance of phosphorus, and hypophosphatemia. The combination of hypocalcemia and hypophosphatemia causes impaired mineralization of bone that results in rickets and osteomalacia (Liberman and Marx, 2001). Genetic Heterogeneity of Vitamin D-Dependent Rickets Vitamin D-dependent rickets type 1A (VDDR1A) is due to an enzymatic defect in synthesis of the active form of vitamin D caused by mutation in the CYP27B1 gene. VDDR1B (600081) is a form of rickets due to mutation in the gene encoding a vitamin D 25-hydroxylase (CYP2R1; 608713), another enzyme necessary for the synthesis of active vitamin D. Vitamin D-dependent rickets type 2A (VDDR2A; 277440) is caused by end-organ unresponsiveness of active vitamin D due to mutation in the gene encoding the vitamin D receptor (VDR; 601769). VDDR2B 600785 is an unusual form of end-organ unresponsiveness to active vitamin D due to an abnormal protein (see HNRNPC, 164020) that interferes with the function of the VDR. Other Forms of Hypophosphatemic Rickets For a discussion of other forms of hypophosphatemic rickets, see ADHR (193100).
Chronic degenerative changes in the glomeruli characterized by loss of cellularity of glomerular capillary tufts and acellular deposition of immunoglobulins.
A syndrome characterized by hematuria with dysmorphic red blood cells, red blood cell casts, and proteinuria; systemic manifestations may be present, including hypertension, edema, oliguria.
A type of mesangiocapillary glomerulonephritis that is characterized by immune deposits on the endothelial side of the GLOMERULAR BASEMENT MEMBRANE leading to splitting and reduplication of the basement membrane.
C3 glomerulopathy (C3G) is a complex ultra-rare complement-mediated renal disease caused by uncontrolled activation of the complement alternative pathway (AP) in the fluid phase (as opposed to cell surface) that is rarely inherited in a simple mendelian fashion. C3G affects individuals of all ages, with a median age at diagnosis of 23 years. Individuals with C3G typically present with hematuria, proteinuria, hematuria and proteinuria, acute nephritic syndrome or nephrotic syndrome, and low levels of the complement component C3. Spontaneous remission of C3G is uncommon, and about half of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis, occasionally developing the late comorbidity of impaired visual acuity.
Glomerulonephritis characterized by proliferation of endothelial or mesangial cells, affecting the glomeruli in a focal and segmental pattern.
Diffuse sclerosis of the mesangium, as manifestated by diffuse mesangial matrix expansion.
Glomerulonephritis characterized by the presence of Cong-red negative microfibrils in the mesangium and capillary walls of the glomeruli. It is associated with marked proteinuria and leads to progressive renal failure.
Chronic kidney disease resulting from deposition of urate crystals or microtophi in the medullary interstitium.
A kidney disorder that results from the damage of the renal arteries or veins. It may lead to renal dysfunction and/or hypertension.
A homogenous cyst located in the kidney.
Diabetes insipidus caused by excessive intake of water due to psychological factors or damage to the thirst-regulating mechanism.
Inflammation of both the urethra and the trigone of the urinary bladder.
A reactive inflammatory disorder affecting the bladder. It is characterized by the development of small cysts in the bladder wall. The cysts are lined by metaplastic glandular cells.
An abnormal connection (fistula) between the rectum and the urethra.
A benign neoplasm arising from soft tissue of the prostate. It is characterized by the presence of spindle-shaped fibroblasts.
Squeezing of the urethra secondary to enlargement of the prostate gland, resulting in voiding symptoms (straining to void, slow urine stream, and incomplete emptying of the bladder).
Bleeding originating from the prostate gland.
Bleeding originating from the vas deferens.
Bleeding originating from the spermatic cord.
Penile length more than 2 SD above the mean for age.
Acute inflammation of the fallopian tube. It is most often caused by Neisseria gonorrhoeae and Chlamydia trachomatis infections. The infections usually originate in the vagina and ascend to the fallopian tube. Symptoms include abdominal, pelvic, and lower back pain, pain during ovulation and sexual intercourse, fever, nausea, and vomiting. Complications include infertility and ectopic pregnancy.
Chronic inflammation of the fallopian tube. It usually follows an acute inflammatory attack.
Formation of nodules in the isthmus of the fallopian tube due to fallopian tube diverticulosis. It may cause infertility or ectopic pregnancy.
Inflammation of both the ENDOMETRIUM and the MYOMETRIUM, usually caused by infections after a CESAREAN SECTION.
Acute inflammation of the cervix. Clinical manifestations include mucopurulent vaginal discharge and burning sensation.
Inflammation of the vulvar vestibular region at the entrance of the VAGINA, generally involving surface mucosa and submucosal vestibular glands. It is characterized by ERYTHEMA and chronic recurrent pain in this area.
A cystic form of endometriosis affecting the ovary. It may or may not be associated with endometriosis in other areas in the pelvis.
A benign pathologic process characterized by the transformation of the mesothelium into fallopian tube epithelium. It occurs in the peritoneum and may affect the serosa surface of the uterus and the adnexa. It may be asymptomatic or present as pelvic pain.
Abnormal growth of endometrial cells (which are normally limited to the uterus) within the cervix.
An abnormal communication between a female reproductive system organ and another organ or cavity.
The presence of a fistula between the vagina and the urethra.
Tearing or disruption of the ovarian tissue.
A twisting of the Fallopian tube. Sudden onset with sharp, colicky pelvic pain associated with nausea, vomiting, bowel, and bladder symptoms is the usual presentation.
A fluid filled sac located in the Fallopian tube.
A condition in which the UTERUS is found tilted backward toward the spine. The uterus is more commonly found in a straight vertical or anteverted (tipped forward) position. Although retroverted uterus is a normal variant position without symptoms, it is sometimes associated with pain, discomfort and other pregnancy complications.
Eversion of the endocervix with protrusion of the central (endocervical) columnar epithelium through the external os of the cervis into the vaginal milieu. [HPO:probinson, pmid:21270291]
The process in which the cervical glandular epithelium is replaced with squamous epithelium.
Irregularity or alteration from normal cervical tissue. The spatial orientation of the cervical cells is often aberrant due to the lack of an organized growth process. 2005
The presence of whitish patches on the mucosal surface of the cervix. Histologic examination reveals hyperkeratosis. In a minority of cases, underlying dysplasia or carcinoma in situ is present.
A narrowing of the vagina owing to scar formation.
Hydrometrocolpos is an accumulation of uterine and vaginal secretions as well as menstrual blood in the uterus and vagina.
The presence of glandular structures in the vagina.
A benign polypoid lesion that arises from the vulva.
A morphologic finding indicating the transformation of the epithelial cells in a breast tissue sample to cells with abundant eosinophilic cytoplasm.
The presence of nipples that instead of pointing outward are retracted inwards.
A type of pregnancy in which the EMBRYO IMPLANTATION occurs in the horn of the UTERUS instead of in the uterine cavity, i.e. at the junction of the uterus and one of the FALLOPIAN TUBES.
MULTIPLE PREGNANCY with EMBRYO IMPLANTATION occuring at different locations, involving both an intrauterine site and an extrauterine (ECTOPIC PREGNANCY) site.
Pregnancy loss at less than 14 weeks 0 days gestation.
Pregnancy loss between 14 weeks 0 days and 21 weeks 6 days gestation.
Excessive blood loss prior to onset of labor.
In a woman with a normal weight pre-pregnancy body mass index (BMI), i.e. 18.5-24.9, the weight gained during pregnancy exceeds a total weight gain of 35 lbs. In a woman with an underweight pre-pregnancy body mass index (BMI), i.e. less than 18.5, the weight gained during pregnancy exceeds a total weight gain of 40 lbs. In a woman with an overweight pre-pregnancy body mass index (BMI), i.e. 25.0-29.9, the weight gained during pregnancy exceeds a total weight gain of 25 lbs. In a woman with an obese pre-pregnancy body mass index (BMI), i.e. greater than 30, the weight gained during pregnancy exceeds a total weight gain of 20 lbs. These standards are supported for the whole population irrespective of height, race or ethnicity.
Fetal death after 22 week gestation affecting management of mother
The discharge of amniotic fluid vaginally due to a tear or rupture in the amniotic membrane.
An amnion with nodular deposits of squamous and cellular debris with varying staging of re-epithelialization.
The occurrence of a pregnancy complication during childbirth, which includes both labor (the process of childbirth) and delivery (the birth itself).
A birth complication caused by impaction of the anterior shoulder against the maternal symphysis pubis that requires additional maneuvers to relieve impaction of the fetal shoulder and allow for delivery.
A single uterine contraction lasting greater than 2 minutes.
A situation in which the umbilical cord is ahead of the presenting fetal part. If the cord becomes compressed it may cut off the flow of blood to the baby.
Pregnancy complication where fetal blood vessels, normally inside the umbilical cord, are left unprotected and cross FETAL MEMBRANES. It is associated with antepartum bleeding and FETAL DEATH and STILLBIRTH due to exsanguination.
Cumulative blood loss of greater than or equal to 1000 ML or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours following the birth process (includes intrapartum loss). (reVITALize)
Infection of the endometrium, decidua and/or myometrium occurring at any time between birth and 42 days postpartum.
A non-neoplastic or neoplastic disorder occurring during the period from about five months before birth to one month after birth.
Episodes of cyanosis during the perinatal period.
A pathological increase in the effort and frequency or breathing movements during the perinatal period.
A syndrome that results from a group of infections that affect the fetus or the newborn. The group of infections includes Toxoplasma gondii, rubella, cytomegalovirus, herpes simplex virus, and other infections. The other infections include varicella-zoster virus, hepatitis B virus, human immunodeficiency virus, parvovirus B19, and syphilis. Signs and symptoms include fever, feeding difficulties, petechial rash, jaundice, hepatosplenomegaly, chorioretinitis, and microcephaly.
Inflammation of the lacrimal sac in a newborn due to blocked drainage of tears or infection.
Bleeding within the cerebral ventricles occurring around the time of birth.
A condition of the newborn characterized by the destruction of red blood cells initiated by the transmission of anti-A or anti-B antibodies from a mother to the child via the placenta against A or B antigens of the newborn's blood.
Encephalopathy in infants due to high levels of unconjugated bilirubin that are a result of Rh incompatibility between the mother and the fetus.
Jaundice in an otherwise healthy breast-fed newborn. It appears four to seven days after birth, lasts longer than the physiologic jaundice, and there are no identifiable causes.
A syndrome characterized by persistent jaundice, hemolytic anemia, and hepatomegaly in a newborn. It is characterized by the presence of inspissated bile plugs in the bile ducts.
An infant that was born to a mother who persistently had high glucose blood levels during pregnancy. The infants of diabetic mothers are large for their gestational age and may develop hypoglycemic episodes soon after birth.
A transient colonic dysfunction in the newborn characterized by the delayed passage of meconium and associated intestinal dilatation.
Inflammation of the peritoneum caused by an intrauterine intestinal perforation leading to presence of meconium within the fetal peritoneal cavity. This is frequently seen as intra-abdominal calcifications on imaging.
An abnormality of the placenta in which there are numerous cystic spaces within the placenta as well as placental enlargement.
A disorder observed in a newborn who was exposed to chloramphenicol. Manifestations include hypotension, cyanosis, cardiovascular collapse and/or death.
Nocturnal enuresis, or nightly bedwetting in children more than 7 years of age, affects about 10% of 7-year-old children, with a wide range of frequencies between populations. The affliction is often linked to major social maladjustments and occupies considerable time in general medical practice. From the age of 7, there is a spontaneous cure rate of 15% per year, such that few remain affected after the age of 16 years. There are 2 types of nocturnal enuresis: type I, the primary form (PNE), with at least 3 nightly episodes in children older than 7 years, where the child has always had the disorder, and type II, or secondary type, where the child has been dry for at least 6 months but enuresis has recurred (summary by Eiberg et al., 1995). Genetic Heterogeneity of Nocturnal Enuresis ENUR1 has been mapped to chromosome 13q, and ENUR2 has been mapped to chromosome 12q.
Involuntary discharge of URINE during the daytime while one is awake.
Schizoaffective disorder is a mental health condition that includes features of both schizophrenia and a mood disorder such as bipolar disorder or depression. The prefix ""schizo-"" refers to the psychotic symptoms of schizophrenia that affect a person's thinking, sense of self, and perceptions. The term ""-affective"" refers to extreme shifts in mood, energy, and behavior.Schizoaffective disorder has a wide range of signs and symptoms that make it challenging to diagnose. Its features overlap significantly with those of schizophrenia and bipolar disorder, and there is debate about whether schizoaffective disorder should be considered a separate diagnosis or a subtype of one of these other conditions.Signs and symptoms of psychosis in people with schizoaffective disorder include false perceptions called hallucinations, such as hearing voices no one else can hear or experiencing visions, smells, or tactile (touch) sensations. Strongly held false beliefs (delusions) are also a characteristic feature. For example, affected individuals may be certain that they are a particular historical figure or that they are being plotted against or controlled by others.There are two major types of schizoaffective disorder, based on which mood disorder is involved: the bipolar type and the depressive type. The bipolar type includes both dramatic ""highs,"" called manic episodes, and ""lows,"" called depressive episodes. The depressive type includes only depressive episodes. Manic episodes are characterized by increased energy and activity, irritability, restlessness, an inability to sleep, and reckless behavior. Depressive episodes are marked by low energy and activity, a feeling of hopelessness, and an inability to perform everyday tasks.The psychosis and mood problems associated with schizoaffective disorder usually become evident in adolescence or young adulthood. People with this condition often have difficulty functioning at school, at work, and in social settings. Disordered thinking and concentration, inappropriate emotional responses, erratic speech and behavior, and difficulty with personal hygiene and everyday tasks are also common. People with schizoaffective disorder have a higher risk of substance abuse problems and dying by suicide than the general population.
An anxiety disorder characterized by excessive and difficult-to-control worry about a number of life situations. The worry is accompanied by restlessness, fatigue, inability to concentrate, irritability, muscle tension, and/or sleep disturbance and lasts for at least 6 months.
Any of various diseases affecting the white matter of the central nervous system.
A neurologic disorder that is caused by inflammation across both sides of one level, or segment, of the spinal cord. (from NINDS)
Circumscribed collections of suppurative material occurring in the spinal or intracranial EPIDURAL SPACE. The majority of epidural abscesses occur in the spinal canal and are associated with OSTEOMYELITIS of a vertebral body; ANALGESIA, EPIDURAL; and other conditions. Clinical manifestations include local and radicular pain, weakness, sensory loss, URINARY INCONTINENCE, and FECAL INCONTINENCE. Cranial epidural abscesses are usually associated with OSTEOMYELITIS of a cranial bone, SINUSITIS, or OTITIS MEDIA. (From Adams et al., Principles of Neurology, 6th ed, p710 and pp1240-1; J Neurol Neurosurg Psychiatry 1998 Aug;65(2):209-12)
Formation or presence of a blood clot (THROMBUS) in the LATERAL SINUSES. This condition is often associated with ear infections (OTITIS MEDIA or MASTOIDITIS) without antibiotic treatment. In developed nations, lateral sinus thrombosis can result from CRANIOCEREBRAL TRAUMA; BRAIN NEOPLASMS; NEUROSURGICAL PROCEDURES; THROMBOPHILIA; and other conditions. Clinical features include HEADACHE; VERTIGO; and increased intracranial pressure.
Abnormal deposits of calcium in the cerebral tissue.
A cerebrospinal fluid-filled pouch or sac-like protrusion of the arachnoid, dura mater, or nerve root sheath which may contain neural tissue.
Headache in erect position, after lumbar puncture; due to lowering of intracranial pressure by leakage of cerebrospinal fluid through the needle tract.
A neurobehavioral syndrome associated with bilateral medial temporal lobe dysfunction. Clinical manifestations include oral exploratory behavior; tactile exploratory behavior; hypersexuality; BULIMIA; MEMORY DISORDERS; placidity; and an inability to recognize objects or faces. This disorder may result from a variety of conditions, including CRANIOCEREBRAL TRAUMA; infections; ALZHEIMER DISEASE; PICK DISEASE OF THE BRAIN; and CEREBROVASCULAR DISORDERS.
Ichthyosis (usually present from infancy), mental retardation, epileptic seizures, hypogonadism with eunuchoid appearance, and occasional short stature. The male/female ratio is 2:1.
A disorder of the central nervous system characterized by gradual and progressive loss of neural tissue and neurologic function.
A language disorder in mentally retarded but educable children who have the ability to learn words and to talk, without knowing what they are talking about. They love to chatter, but think illogically.
PLA2G6-associated neurodegeneration (PLAN) comprises a continuum of three phenotypes with overlapping clinical and radiologic features: Infantile neuroaxonal dystrophy (INAD). Atypical neuroaxonal dystrophy (atypical NAD). PLA2G6-related dystonia-parkinsonism. INAD usually begins between ages six months and three years with psychomotor regression or delay, hypotonia, and progressive spastic tetraparesis. Many affected children never learn to walk or lose the ability shortly after attaining it. Strabismus, nystagmus, and optic atrophy are common. Disease progression is rapid, resulting in severe spasticity, progressive cognitive decline, and visual impairment. Many affected children do not survive beyond their first decade. Atypical NAD shows more phenotypic variability than INAD. In general, onset is in early childhood but can be as late as the end of the second decade. The presenting signs may be gait instability, ataxia, or speech delay and autistic features, which are sometimes the only evidence of disease for a year or more. Strabismus, nystagmus, and optic atrophy are common. Neuropsychiatric disturbances including impulsivity, poor attention span, hyperactivity, and emotional lability are also common. The course is fairly stable during early childhood and resembles static encephalopathy but is followed by neurologic deterioration between ages seven and 12 years. PLA2G6-related dystonia-parkinsonism has a variable age of onset, but most individuals present in early adulthood with gait disturbance or neuropsychiatric changes. Affected individuals consistently develop dystonia and parkinsonism (which may be accompanied by rapid cognitive decline) in their late teens to early twenties. Dystonia is most common in the hands and feet but may be more generalized. The most common features of parkinsonism in these individuals are bradykinesia, resting tremor, rigidity, and postural instability.
Alexander disease is a progressive disorder of cerebral white matter that predominantly affects infants and children and has variable life expectancy. The later-onset forms present with a slower clinical course. The infantile form comprises about 42% of affected individuals, the juvenile form about 22%, and the adult form about 33%. A neonatal form is also recognized. The neonatal form leads to severe disability or death within two years. Characteristics include seizures, hydrocephalus, severe motor and intellectual disability, and elevated CSF protein concentration. MRI shows severe white matter abnormalities with involvement of the basal ganglia and cerebellum. The infantile form presents in the first two years of life, typically with progressive psychomotor retardation with loss of developmental milestones, megalencephaly, frontal bossing, and seizures. Other findings include hyperreflexia and pyramidal signs, ataxia, and occasional hydrocephalus secondary to aqueductal stenosis. Affected children survive weeks to several years. The juvenile form usually presents between ages four and ten years, occasionally in the mid-teens. Findings can include bulbar/pseudobulbar signs, ataxia, gradual loss of intellectual function, seizures, normocephaly or megalencephaly, and breathing problems. Survival ranges from the early teens to the 20s-30s. The adult form is the most variable.
A progressive neurodegenerative disorder caused by a disruption in the connection between the striatum and the substantia nigra. It is a type of multiple system atrophy (MSA). Signs and symptoms include rigidity, instability, impaired speech, and slow movements.
A relatively common disorder characterized by a fairly specific pattern of tremors which are most prominent in the upper extremities and neck, inducing titubations of the head. The tremor is usually mild, but when severe may be disabling. An autosomal dominant pattern of inheritance may occur in some families (i.e., familial tremor). (Mov Disord 1988;13(1):5-10)
A form of dyskinetic cerebral palsy with slow, writhing movements that are often repetitive, sinuous, and rhythmic.
A form of athetoid cerebral palsy with bilateral involuntary movements.
Cerebellar ataxia that is transmitted from parent to child.
A form of dementia characterized by brain lesions in the deep white-matter, also known as subcortical dementia.
A form of spastic cerebral palsy affecting two limbs; usually the legs are affected more than the arms.
A form of spastic cerebral palsy affecting the arm and/or leg on one side of the body. An ipsilateral upper and/or lower extremity is affected.
A form of spastic cerebral palsy affecting only one limb
Paralysis of the nerves located in the legs.
A type of seizure characterized by laughing or an outburst of laughing as a major feature.
A partial seizure characterized by impairment or loss of consciousness. [HPO:curators]
Prolonged contraction of the muscles, as the result of an epileptic discharge.
Seizures characterized by a sudden loss or diminution of muscle tone, which may be fragmentary, confined to a segment (limb, jaw, head), or massive, leading to a slumping to the ground . [HPO:jalbers, HPO:probinson]
Idiopathic generalized epilepsy is a broad term that encompasses several common seizure phenotypes, classically including childhood absence epilepsy (CAE, ECA; see 600131), juvenile absence epilepsy (JAE, EJA; see 607631), juvenile myoclonic epilepsy (JME, EJM; see 254770), and epilepsy with grand mal seizures on awakening (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). These recurrent seizures occur in the absence of detectable brain lesions and/or metabolic abnormalities. Seizures are initially generalized with a bilateral, synchronous, generalized, symmetrical EEG discharge (Zara et al., 1995; Lu and Wang, 2009). See also childhood absence epilepsy (ECA1; 600131), which has also been mapped to 8q24. Of note, benign neonatal epilepsy 2 (EBN2; 121201) is caused by mutation in the KCNQ3 gene (602232) on 8q24. Genetic Heterogeneity of Idiopathic Generalized Epilepsy EIG1 has been mapped to chromosome 8q24. Other loci or genes associated with EIG include EIG2 (606972) on 14q23; EIG3 (608762) on 9q32; EIG4 (609750) on 10q25; EIG5 (611934) on 10p11; EIG6 (611942), caused by mutation in the CACNA1H gene (607904) on 16p; EIG7 (604827) on 15q14; EIG8 (612899), caused by mutation in the CASR gene (601199) on 3q13.3-q21; EIG9 (607682), caused by mutation in the CACNB4 gene (601949) on 2q23; EIG10 (613060), caused by mutation in the GABRD gene (137163) on 1p36; EIG11 (607628), caused by variation in the CLCN2 gene (600570) on 3q36; EIG12 (614847), caused by mutation in the SLC2A1 gene (138140) on 1p34; EIG13 (611136), caused by mutation in the GABRA1 gene (137160) on 5q34; EIG14 (616685), caused by mutation in the SLC12A5 gene (606726) on 20q12; and EIG15 (618357), caused by mutation in the RORB gene (601972) on 9q22.
A condition marked by recurrent seizures that occur during the first 4-6 weeks of life despite an otherwise benign neonatal course. Autosomal dominant familial and sporadic forms have been identified. Seizures generally consist of brief episodes of tonic posturing and other movements, apnea, eye deviations, and blood pressure fluctuations. These tend to remit after the 6th week of life. The risk of developing epilepsy at an older age is moderately increased in the familial form of this disorder. (Neurologia 1996 Feb;11(2):51-5)
Juvenile myoclonic epilepsy is a subtype of idiopathic generalized epilepsy (EIG; see 600669) affecting up to 26% of all individuals with EIG. Individuals with JME have afebrile seizures only, with onset in adolescence of myoclonic jerks. Myoclonic jerks occur usually in the morning (Janz and Durner, 1997). Genetic Heterogeneity of Juvenile Myoclonic Seizures Susceptibility to EJM can be conferred by variation in several other genes: EJM5 (611136), by variation in the GABRA1 gene (137160) on 5q34; EJM6 (see 607682), by variation in the CACNB4 gene (601949) on 2q23; EJM7 (see 613060), by variation in the GABRD gene (137163) on 1p36; EJM8 (see 607628), by variation in the CLCN2 gene (600570) on 3q27; and EJM10 (617924), by variation in the ICK gene (612325) on chromosome 6p12. In addition, EJM loci have been identified by linkage analysis: EJM2 (see 604827) on 15q14, EJM3 (608816) on 6p21, EJM4 (611364) on 5q12-q14, and EJM9 (614280) on 2q33-q36.
Early infantile epileptic encephalopathy is characterized by onset during the first months of life of erratic refractory seizures, usually myoclonic. The prognosis is poor, and most children with the condition either die within 1 to 2 years after birth or survive in a persistent vegetative state. The EEG pattern often shows a suppression-burst pattern with high-voltage bursts of slow waves mixed with multifocal spikes alternating with isoelectric suppression phases (Molinari et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
A subtype of epilepsy characterized by seizures that are consistently provoked by a certain specific stimulus. Auditory, visual, and somatosensory stimuli as well as the acts of writing, reading, eating, and decision making are examples of events or activities that may induce seizure activity in affected individuals. (From Neurol Clin 1994 Feb;12(1):57-8)
Paroxysmal episodes of intense, acute periumbilical pain that lasts for one or more hours with intervening periods of usual health lasting weeks to months, with no evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the symptoms. The pain interferes with normal activities and is associated with at least two of the following symptoms: anorexia, nausea, vomiting, headache, photophobia, and/or pallor.
A migraine disorder characterized by episodes that are preceded by focal neurological symptoms originating in the brainstem.
Facial myokymia is a fine fibrillary activity of one or more muscles innervated by the facial nerve (the seventh cranial nerve).
Weakness or paralysis of muscles in the forearm or hand due to damage of the lower brachial plexus.
For a general phenotypic description and a discussion of genetic heterogeneity of Charcot-Marie-Tooth disease type 1, see CMT1B (118200). CMT1A is the most common form of CMT. The average age of onset of clinical symptoms is 12.2 +/- 7.3 years. Slow nerve conduction velocity (NCV) less than 38 m/s is highly diagnostic and is a 100% penetrant phenotype independent of age (Lupski et al., 1991, 1992).
Charcot-Marie-Tooth disease is a sensorineural peripheral polyneuropathy. Affecting approximately 1 in 2,500 individuals, Charcot-Marie-Tooth disease is the most common inherited disorder of the peripheral nervous system (Skre, 1974). Autosomal dominant, autosomal recessive, and X-linked forms have been recognized. Classification On the basis of electrophysiologic properties and histopathology, CMT has been divided into primary peripheral demyelinating (type 1, or HMSNI) and primary peripheral axonal (type 2, or HMSNII) neuropathies. The demyelinating neuropathies classified as CMT type 1 are characterized by severely reduced motor NCVs (less than 38 m/s) and segmental demyelination and remyelination with onion bulb formations on nerve biopsy. The axonal neuropathies classified as CMT type 2 are characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy (see CMT2A1; 118210). Distal hereditary motor neuropathy (dHMN) (see 158590), or spinal CMT, is characterized by exclusive motor involvement and sparing of sensory nerves (Pareyson, 1999). McAlpine (1989) proposed that the forms of CMT with very slow nerve conduction be given the gene symbol CMT1A (118220) and CMT1B, CMT1A being the gene on chromosome 17 and CMT1B being the gene on chromosome 1. CMT2 was the proposed symbol for the autosomal locus responsible for the moderately slow nerve conduction form of the disease (axonal). For a phenotypic description and discussion of genetic heterogeneity of the various subtypes of CMT, see CMTX1 (302800), CMT2A1 (118210), CMT3 (DSS; 145900), CMT4A (214400), and CMTDIB (606482). Genetic Heterogeneity of Autosomal Dominant Demyelinating CMT1 Autosomal dominant demyelinating CMT1 is genetically heterogeneous disorder and can be caused by mutations in different genes (see CMT1A, 118220; CMT1C, 601098; CMT1D, 607678), CMT1E (607734), CMT1F (607734), and CMT1G (618279). See also 608236 for a related phenotype characterized by isolated slowed nerve conduction velocities (NCVs).
For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant Charcot-Marie-Tooth disease type 1, see CMT1B (118200).
Any nerve disorder affecting the axon of a nerve.
Demyelinating neuropathy is characterized by slow nerve conduction velocities with reduced amplitudes of sensory/motor nerve conduction and prolonged distal latencies.
A diffuse or multifocal peripheral neuropathy caused by the effects of a distant neoplasm. It may be attributed, in part, to the immune response to neoplasm-elaborated proteins. The neuropathy may be sensory, motor, mixed or autonomic. It may be the initial presentation of an occult neoplasm. Detection and resection of the neoplasm may result in cure.
Polyneuropathy that is caused by exposure to toxins.
Oculopharyngeal muscular dystrophy (OPMD) is characterized by ptosis and swallowing difficulties due to selective involvement of the muscles of the eyelid and pharynx, respectively. The mean age of onset of ptosis is usually 48 years and onset of dysphagia is 50 years. Early symptoms of dysphagia are increased time needed to consume a meal and an acquired avoidance of dry foods. Swallowing difficulties determine prognosis, and increase the risk for potentially life-threatening aspiration pneumonia and poor nutrition. Other signs observed as the disease progresses are tongue weakness (82%), proximal lower-extremity weakness (71%), wet voice due to pooling of saliva (67%), limitation of upward gaze (61%), facial muscle weakness (43%), and proximal upper extremity weakness (38%). Involvement of the nervous system occurs on occasion. Severe OPMD, representing 5% to 10% of all OPMD, is characterized by onset of ptosis and dysphagia before age 45 years and incapacitating proximal leg weakness that starts before age 60 years. Some individuals with severe involvement eventually need a wheelchair.
A rare disorder with characteristics of pseudohypertrophy of muscles due to longstanding hypothyroidism. Prevalence is unknown. The syndrome usually presents between 18 months and 10 years but has been reported at earlier ages including during the neonatal period. Patients present with clinical features of hypothyroidism, including decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice. Pseudohypertrophy involves the muscles of the extremities, limb girdle, trunk, hands and feet but is more prominent in the limbs, resulting in an athletic appearance. Hypothyroidism, or thyroid hormone deficiency, may be congenital and may be permanent or transient.
A syndrome of generalized poor muscle tone and muscle weakness presenting in a newborn infant.
Classic Cornelia de Lange syndrome (CdLS) is characterized by distinctive facial features, growth retardation (prenatal onset; <5th centile throughout life), hirsutism, and upper-limb reduction defects that range from subtle phalangeal abnormalities to oligodactyly (missing digits). Craniofacial features include synophrys, highly arched eyebrows, long eyelashes, short nose with anteverted nares, small widely spaced teeth, and microcephaly. IQ ranges from below 30 to 102 (mean: 53). Many individuals demonstrate autistic and self-destructive tendencies. Frequent findings include cardiac septal defects, gastrointestinal dysfunction, hearing loss, myopia, and cryptorchidism or hypoplastic genitalia. Individuals with a milder phenotype have less severe growth, cognitive, and limb involvement, but often have facial features consistent with CdLS.
A group of rare inherited disorders characterized by a deficiency of enzymes that are involved in metabolic pathways that affect muscles. The disorders are characterized by muscle dysfunction.
A non-neoplastic disorder affecting the skeletal muscles. It is caused by damage to muscle fibers either by excessive intake of corticosteroids (steroid treatment) or high levels of endogenous corticosteroids due to hormonal abnormalities. Patients usually present with weakness mainly in the proximal muscles of the upper and lower extremities and the neck flexors.
Absence of the anterior chamber of the eye owing to a developmental defect.
Atrophy of the eyeball with blindness and decreased intraocular pressure due to end-stage intraocular disease.
A localized detachment of the vitreous from the retina due to the accumulation of blood. When localized in the macular area, it results in sudden profound loss of vision. Subhyaloid premacular hemorrhage is typically characterized by a circumscribed, round or dumb-bell shaped, bright red mound of blood beneath the internal limiting membrane (ILM) or between the ILM and hyaloid face, in or near to the central macular area.
Accumulation of blood located beneath the neurosensory retina in the space between the neurosensory retina and the retinal pigment epithelium.
Accumulation of intraretinal fluid and protein in the macula, which may result in swelling and decreased central vision.
Fluffy white patch on the retina, representing localized areas of dense white swelling of the retinal nerve fibre layer. They often have a zigzag internal structure, a feathered edge but an otherwise well-delineated form and an approximately 1 mm dimension; they project slightly into the vitreous and sometimes deflect retinal vessels. [PMID:6169833]
A type of retinal detachment associated with a retinal tear, that is, with a break in the retina that allows fluid to pass from the vitreous space into the subretinal space between the sensory retina and the retinal pigment epithelium.
New, damaging blood vessels that grow beneath the retina. These blood vessels grow in an area called the choroid.
A genetic disorder affecting primarily males. It is caused by mutations of the XLRS1 gene mapped to chromosome Xp22. It affects the cells of the retina, resulting in retinal degeneration and poor eyesight.
An autosomal recessive and rarely autosomal dominant inherited disorder caused by mutations in the ABCA4 or ELOVL4 genes respectively. It is characterized by macular degeneration that begins in late childhood resulting in progressive loss of vision.
Usher syndrome is a condition characterized by partial or total hearing loss and vision loss that worsens over time. The hearing loss is classified as sensorineural, which means that it is caused by abnormalities of the inner ear. The loss of vision is caused by an eye disease called retinitis pigmentosa (RP), which affects the layer of light-sensitive tissue at the back of the eye (the retina). Vision loss occurs as the light-sensing cells of the retina gradually deteriorate. Night vision loss begins first, followed by blind spots that develop in the side (peripheral) vision. Over time, these blind spots enlarge and merge to produce tunnel vision. In some cases, vision is further impaired by clouding of the lens of the eye (cataracts). However, many people with retinitis pigmentosa retain some central vision throughout their lives.Researchers have identified three major types of Usher syndrome, designated as types I, II, and III. These types are distinguished by the severity of hearing loss, the presence or absence of balance problems, and the age at which signs and symptoms appear. The types are further divided into subtypes based on their genetic cause.Most individuals with Usher syndrome type I are born with severe to profound hearing loss. Progressive vision loss caused by retinitis pigmentosa becomes apparent in childhood. This type of Usher syndrome also causes abnormalities of the vestibular system, which is the part of the inner ear that helps maintain the body's balance and orientation in space. As a result of the vestibular abnormalities, children with the condition have trouble with balance. They begin sitting independently and walking later than usual, and they may have difficulty riding a bicycle and playing certain sports.Usher syndrome type II is characterized by hearing loss from birth and progressive vision loss that begins in adolescence or adulthood. The hearing loss associated with this form of Usher syndrome ranges from mild to severe and mainly affects the ability to hear high-frequency sounds. For example, it is difficult for affected individuals to hear high, soft speech sounds, such as those of the letters d and t. The degree of hearing loss varies within and among families with this condition, and it may become more severe over time. Unlike the other forms of Usher syndrome, type II is not associated with vestibular abnormalities that cause difficulties with balance.People with Usher syndrome type III experience hearing loss and vision loss beginning somewhat later in life. Unlike the other forms of Usher syndrome, type III is usually associated with normal hearing at birth. Hearing loss typically begins during late childhood or adolescence, after the development of speech, and becomes more severe over time. By middle age, most affected individuals have profound hearing loss. Vision loss caused by retinitis pigmentosa also develops in late childhood or adolescence. Some people with Usher syndrome type III develop vestibular abnormalities that cause problems with balance.
Any disease or disorder of the ciliary body.
An epithelium-lined cyst located in the iris.
A closed sac, having a distinct membrane and division compared to the nearby tissue. located within the anterior chamber. The sac that may contain air, fluids, or semi-solid material.
A deviation from the normal circular shape of the pupil
Ectopia pupillae is a congenital eye malformation in which the pupils are displaced from their normal central position.
A cataract which affects the layer of the lens surrounding the nucleus, i.e., the lens cortex. It is identified by its unique wedge or spoke appearance.
A type of cataract with punctate opacities of the lens. [HPO:probinson]
A severe form of myopia with greater than -6.00 diopters.
A visual anomaly in which images appear distorted. A grid of straight lines appears wavy and parts of the grid may appear blank.
Hazy ring around bright lights seen by some patients with refractive error or optical defects, e.g. cataracts, or corneal swelling.
Perception of more than one image when viewing with one eye.
Reduced or abnormal sight in the peripheral visual field.
A scotoma (area of diminished vision within the visual field) located between the central point of fixation and the blind spot with a roughly horizontal oval shape.
A localized defect in the visual field bordered by an area of normal vision. This occurs with a variety of EYE DISEASES (e.g., RETINAL DISEASES and GLAUCOMA), OPTIC NERVE DISEASES, and other conditions.
A rare genetic retinal dystrophy with characteristics of irregular, sharply defined, yellowish-white lesions of variable size that are distributed mainly in the nasal equatorial region of the retina, with a tendency to confluence, that are not associated with any vascular or optic nerve abnormalities. They frequently manifest as mild and stationary night blindness.
A condition consisting of inflammatory eye disease usually presenting as interstitial KERATITIS, vestibuloauditory dysfunction, and large- to medium-vessel vasculitis.
Schnyder corneal dystrophy (SCCD), also known as Schnyder crystalline corneal dystrophy, is an autosomal dominant eye disease characterized by abnormal deposition of cholesterol and phospholipids in the cornea. The consequent corneal opacification is progressive and bilateral, resulting in glare and loss of vision that is postulated to be caused by light scattering. Patients demonstrate a characteristic pattern of corneal opacification dependent on age, and only half have crystalline corneal cholesterol deposits. Patients with noncrystalline disease have a more subtle presentation with only corneal haze, which may be difficult to diagnose (summary by Nickerson et al., 2013).
Corneal guttata are droplet-like accumulations of non-banded collagen on the posterior surface of Descemet's membrane. The presence of focal thickenings of Descemet's membrane histologically named guttae. Cornea guttata can be easily diagnosed in vivo and ex vivo by means of specular microscopy as it gives dark areas where no endothelial cells are visible.
Reduced ability of the cornea to respond to stimulation.
Edema (swelling) of the bulbar conjunctiva.
This term refers to the loss of eyelashes that were previously present.
Swelling of the lacrimal duct due to excess fluid.
A lymphoma that arises from the structures of the orbit. Representative examples include mucosa-associated lymphoid tissue lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma.
A non-neoplastic or neoplastic disorder affecting the oculomotor nerve (third cranial nerve).
Malfunction of the abducens nerve as manifested by impairment of the ability of the affected eye to be moved outward.
A small angle heterotropia (usually of 10 diopters or less) in which a form of binocular single vision occurs. [ORCID:0000-0003-0986-4123]
A type of cyclotropia (torsion of one or both eye about the visual axis of the eyes) in which the upper poles of the globes are rotated inward (medially) to each other. [ORCID:0000-0003-0986-4123]
A type of cyclotropia (torsion of one or both eye about the visual axis of the eyes) in which the upper poles of the globes are rotated outward (laterally) to each other. [UManchster:psergouniotis]
Tendency for the visual ais of one eye to be higher than that of the other. [ORCID:0000-0003-0986-4123]
A form of latent strabismus (heterophoria) in which, on dissociation, the occluded eye deviates downwards. [ORCID:0000-0003-0986-4123]
A non-neoplastic or neoplastic disorder affecting the trochlear nerve (IVth cranial nerve).
Abducent nerve paralysis with contralateral hemiparesis
Reduced ability to turn the eyes inward in order to focus on a nearby object.
Nystagmus consisting of horizontal to-and-fro eye movements.
Vertical nystagmus may present with either up-beating or down-beating eye movements or both. When present in the straight-ahead position of gaze it is referred to as upbeat nystagmus or downbeat nystagmus.
Rhythmic, involuntary sinusoidal oscillations of one or both eyes. The waveform of pendular nystagmus may occur in any direction. [HPO:probinson]
Nystagmus made apparent by looking to the right or to the left.
Fiber- or rope-like opacities located within the vitreous humor.
A non-neoplastic or neoplastic disorder that affects the middle ear. Representative examples include infection, cholesteatoma, and carcinoma.
Acute otitis media is a short and generally painful infection of the middle ear.
Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.
Otitis media that persists for at least six weeks, and that is associated with otorrhea through a perforated tympanic membrane.
A benign polypoid growth in the middle ear.
A type of hearing impairment affecting primarily the low frequencies of sound (125 Hz to 1000 Hz).
Ischemic or hemorrhagic necrosis of the pituitary gland.
Abnormally low levels of circulating somatotropin.
Type II IGHD is an autosomal dominant disorder characterized by low but detectable levels of growth hormone (GH), variable height deficit and age at presentation, and good response to rhGH. Patients may show anterior pituitary hypoplasia on MRI (summary by Phillips and Cogan, 1994; Alatzoglou and Dattani, 2012).
Laron syndrome is an autosomal recessive disorder characterized by marked short stature that results from failure to generate insulin-like growth factor I (IGF1; 147440) in response to growth hormone (GH; 139250). GH levels are normal or increased. The disorder is caused by dysfunction of the growth hormone receptor. A Laron syndrome-like phenotype associated with immunodeficiency (245590) is caused by a postreceptor defect, i.e., mutation in the STAT5B gene (604260). Patients with mutations in the GHR gene that cause only partial insensitivity to growth hormone have a form of short stature (604271).
Decreased functionality of the female gonads, i.e., of the ovary.
Male patients with hypogonadotropic hypogonadism due to isolated luteinizing hormone (LH) deficiency have normal sexual differentiation but fail to develop spontaneous puberty. Absence of LH alters Leydig cell proliferation and maturation and impairs the onset of normal spermatogenesis, which requires high levels of intratesticular testosterone. Infertility and very low levels of spermatogenesis generally persist in affected men despite long-term exposure to gonadotropin therapy. Female patients exhibit normal pubertal development and menarche, followed by oligomenorrhea and anovulatory secondary amenorrhea (summary by Basciani et al., 2012). For a general phenotypic description and discussion of genetic heterogeneity of hypogonadotropic hypogonadism, see 147950. Reviews Arnhold et al. (2009) noted that the clinical manifestations of female patients with hypogonadotropic hypogonadism due to mutations in LHB are very similar to those of women with hypergonadotropic hypogonadism due to inactivating mutations of the LH receptor (see 238320): all have female external genitalia, spontaneous development of normal pubic hair and breasts at puberty, and normal to late menarche followed by oligoamenorrhea and infertility. Pelvic ultrasound shows a small or normal uterus and normal or enlarged ovaries with cysts. However, women with LHB mutations can be treated with luteinizing hormone or chorionic gonadotropin (CG; 118860) replacement therapy; women with LH receptor mutations are resistant to LH, and no treatment is effective in recovering their fertility.
Congenital isolated adrenocorticotropic hormone deficiency is characterized by severe hypoglycemia in the neonatal period, associated with seizures in about half of cases; prolonged cholestatic jaundice; and very low plasma ACTH levels with no significant response to CRH (122560). Plasma cortisol levels are also extremely low (Vallette-Kasic et al., 2005). TBX19 is required for initiation of transcription of the POMC gene (176830), which produces the precursor peptide from which ACTH is derived (Lamolet et al., 2001).
A reduced ability to secrete prolactin, a protein hormone that is secreted by lactotrophs in the anterior pituitary and that stimulates mammary gland development and milk production.
A condition occurring in women who have had a bilateral salpingo-oophorectomy, with or without hysterectomy, that leaves behind ovarian tissue. This residual ovarian tissue then results in pelvic symptoms such as pain or mass.
The onset of puberty before the age of 8 years in girls.
A reduced ability to secrete gonadotropins, which are protein hormones secreted by gonadotrope cells of the anterior pituitary gland, including the hormones follitropin (FSH) and luteinizing hormone (LH).
A deficiency of the Mullerian inhibiting substance, which is secreted by the Sertoli cells during embryogenesis. It can result in unilateral or bilateral cryptorchidism, testicular regression syndrome and sterility.
A non-neoplastic or neoplastic disorder that affects the endocrine pancreatic tissue (islets of Langerhans). Representative examples include diabetes mellitus and neuroendocrine neoplasms.
diabetes mellitus caused by medicinal substances given to or taken by the patient; concept excludes diabetes resulting from exposure to nonmedicinal chemicals in the environment or drugs of abuse, for which see TOXICOLOGY.
A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.
Autonomic neuropathy that is caused by diabetes mellitus.
Generalized lipodystrophy, the cause of which is not present at birth.
Familial partial lipodystrophy is a rare condition characterized by an abnormal distribution of fatty (adipose) tissue. Adipose tissue is normally found in many parts of the body, including beneath the skin and surrounding the internal organs. It stores fat as a source of energy and also provides cushioning. In people with familial partial lipodystrophy, adipose tissue is lost from the arms, legs, and hips, giving these parts of the body a very muscular appearance. The fat that cannot be stored in the limbs builds up around the face and neck, and inside the abdomen. Excess fat in these areas gives individuals an appearance described as ""cushingoid,"" because it resembles the physical features associated with a hormonal disorder called Cushing disease. This abnormal fat distribution can begin anytime from childhood to adulthood.Abnormal storage of fat in the body can lead to health problems in adulthood. Many people with familial partial lipodystrophy develop insulin resistance, a condition in which the body's tissues cannot adequately respond to insulin, which is a hormone that normally helps to regulate blood sugar levels. Insulin resistance may worsen to become a more serious disease called diabetes mellitus. Some people with familial partial lipodystrophy develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.Most people with familial partial lipodystrophy also have high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia), which can lead to inflammation of the pancreas (pancreatitis). Familial partial lipodystrophy can also cause an abnormal buildup of fats in the liver (hepatic steatosis), which can result in an enlarged liver (hepatomegaly) and abnormal liver function. After puberty, some affected females develop multiple cysts on the ovaries, an increased amount of body hair (hirsutism), and an inability to conceive (infertility), which are likely related to hormonal changes.Researchers have described at least six forms of familial partial lipodystrophy, which are distinguished by their genetic cause. The most common form of familial partial lipodystrophy is type 2, also called Dunnigan disease. In addition to the signs and symptoms described above, some people with this type of the disorder develop muscle weakness (myopathy), abnormalities of the heart muscle (cardiomyopathy), a form of heart disease called coronary artery disease, and problems with the electrical system that coordinates the heartbeat (the conduction system).
HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.
HYPOGLYCEMIA expressed after a meal or FOOD INTAKE. It is also called reactive or stimulative hypoglycemia.
A condition in which hypoglycemia is accompanied by ketosis. This condition may be a manifestation of another condition such as glycogen storage disease, ketone utilization defects, growth hormone deficiency, or cortisol deficiency.
Cushing syndrome as a result of increased glucocorticoids due to medical therapy.
A form of hyperaldosteronism caused by abnormally increased renin levels.
Triple A syndrome is an inherited condition characterized by three specific features: achalasia, Addison disease, and alacrima. Achalasia is a disorder that affects the ability to move food through the esophagus, the tube that carries food from the throat to the stomach. It can lead to severe feeding difficulties and low blood sugar (hypoglycemia). Addison disease, also known as primary adrenal insufficiency, is caused by abnormal function of the small hormone-producing glands on top of each kidney (adrenal glands). The main features of Addison disease include fatigue, loss of appetite, weight loss, low blood pressure, and darkening of the skin. The third major feature of triple A syndrome is a reduced or absent ability to secrete tears (alacrima). Most people with triple A syndrome have all three of these features, although some have only two.Many of the features of triple A syndrome are caused by dysfunction of the autonomic nervous system. This part of the nervous system controls involuntary body processes such as digestion, blood pressure, and body temperature. People with triple A syndrome often experience abnormal sweating, difficulty regulating blood pressure, unequal pupil size (anisocoria), and other signs and symptoms of autonomic nervous system dysfunction (dysautonomia).People with this condition may have other neurological abnormalities, such as developmental delay, intellectual disability, speech problems (dysarthria), and a small head size (microcephaly). In addition, affected individuals commonly experience muscle weakness, movement problems, and nerve abnormalities in their extremities (peripheral neuropathy). Some develop optic atrophy, which is the degeneration (atrophy) of the nerves that carry information from the eyes to the brain. Many of the neurological symptoms of triple A syndrome worsen over time.People with triple A syndrome frequently develop a thickening of the outer layer of skin (hyperkeratosis) on the palms of their hands and the soles of their feet. Other skin abnormalities may also be present in people with this condition.Alacrima is usually the first noticeable sign of triple A syndrome, as it becomes apparent early in life that affected children produce little or no tears while crying. They develop Addison disease and achalasia during childhood or adolescence, and most of the neurologic features of triple A syndrome begin during adulthood. The signs and symptoms of this condition vary among affected individuals, even among members of the same family.
Calcification within the adrenal glands.
Pathological enlargement of the LINGUAL THYROID, ectopic thyroid tissue at the base of the TONGUE. It may cause upper AIRWAY OBSTRUCTION; DYSPHAGIA; or HYPOTHYROIDISM symptoms.
Graves disease in the neonate resulting from transplacental passage of thyrotropin receptor antibody.
A type of hypothyroidism due to an insufficient stimulation of an otherwise normal thyroid gland. Central hypothyroidism is caused by either pituitary (secondary hypothyroidism) or hypothalamic (tertiary hypothyroidism) defects.
Inflammatory disorder of thyroid gland that occurs postpartum due to any partum problem.
A morphologic finding indicating transformation of follicular cells to large cells with abundant eosinophilic and granular cytoplasm (Hurthle cells) in the thyroid gland.
A condition associated with reduced active import of iodide across the basolateral membrane of the follicular cells of the thyroid gland. Inactivating mutations in the SLC5A5 gene encoding the sodium-iodide symporter are responsible for the condition.
Pendred syndrome/nonsyndromic enlarged vestibular aqueduct (PDS/NSEVA) comprises a phenotypic spectrum of sensorineural hearing loss (SNHL) that is usually congenital and often severe to profound (although mild-to-moderate progressive hearing impairment also occurs), vestibular dysfunction, and temporal bone abnormalities (bilateral enlarged vestibular aqueduct with or without cochlear hypoplasia). PDS also includes development of euthyroid goiter in late childhood to early adulthood whereas NSEVA does not.
A type of hyperparathyroidism that occurs following kidney transplantation, which is a treatment for secondary hyperparathyroidism. Although kidney transplantation leads to a normalization of serum calcium and parathyroid hormone in most patients. The state of persistent hypercalcemia and hyperparathyroidism is referred to as tertiary hyperparathyroidism.
A type of hypoparathyroidism with circulating antiparathyroid or anti-calcium sensing receptor antibodies indicative of autoimmunity.
Emaciation in the setting of normal linear growth and intellectual development, which is usually associated with neoplasms involving the anterior hypothalamus in infancy or early childhood.
A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes.
A type of anemia characterized by an normal concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes.
Methemoglobinemia that is caused by exposure to certain drugs (xylocaine and benzene) and nitrate-rich foods.
A state of bone marrow suppression and failure that is caused by a cytotoxic or adverse immunologic response to a drug treatment, leading to a failure of production of red blood cells, white cells and platelets.
Congenital dyserythropoietic anemia type I (CDA I) is characterized by moderate-to-severe macrocytic anemia presenting occasionally in utero as severe anemia associated with hydrops fetalis but more commonly in neonates as hepatomegaly, early jaundice, and intrauterine growth retardation. Some cases present in childhood or adulthood. After the neonatal period, most affected individuals have lifelong moderate anemia, usually accompanied by jaundice and splenomegaly. Secondary hemochromatosis develops with age as a result of increased iron absorption even in those who are not transfused. Distal limb anomalies occur in 4%-14% of affected individuals.
Congenital dyserythropoietic anemia type III is a rare disorder characterized by nonprogressive mild to moderate hemolytic anemia, macrocytosis in the peripheral blood, and giant multinucleated erythroblasts in the bone marrow (Lind et al., 1995). For a discussion of genetic heterogeneity of congenital dyserythropoietic anemia, see 224120.
A type of megaloblastic anemia (i.e., anemia characterized by the presence of erythroblasts that are larger than normal) that improves upon the administration of thiamine.
A hereditary disorder characterized by reduced or absent DELTA-GLOBIN thus effecting the level of HEMOGLOBIN A2, a minor component of adult hemoglobin monitored in the diagnosis of BETA-THALASSEMIA.
A type of sideroblastic anemia that is alleviated by pyridoxine (vitamin B-6) treatment.
A group of inherited hemolytic anemias caused by erythrocyte membrane defects. This includes hereditary pyropoikilocytosis, hereditary spherocytosis and hereditary elliptocytosis.
A rare haemolytic anaemia with manifestations of decreased red cell osmotic fragility due to a defect in cation permeability, resulting in red cell dehydration and mild to moderate compensated haemolysis. Pseudohyperkalaemia (loss of potassium ions from red cells on storage at room temperature) is sometimes observed. Transmission is autosomal dominant.
Aldolase A deficiency is an autosomal recessive disorder associated with hereditary hemolytic anemia (Kishi et al., 1987).
A condition characterized by the presence of a variant of normal hemoglobin (hemoglobin D), which is caused by mutation(s) in the gene encoding the beta subunit of the hemoglobin molecule.
Methemoglobinemia inherited in an autosomal recessive pattern. It is caused by deficiency of the enzyme NADH methemoglobin reductase or the presence of abnormal hemoglobin M. It presents with cyanosis early in life. There is no evidence of cardiopulmonary disease present.
A rare, chronic and relapsing autoimmune disorder of unknown etiology, characterized by the presence of immune thrombocytopenia and autoimmune hemolytic anemia.
Polyagglutination refers to red blood cells that agglutinate upon exposure to almost all human sera, but not to autologous serum or the sera of newborns. The condition becomes apparent during blood typing and cross-matching in the laboratory (summary by Beck, 2000). Tn polyagglutination syndrome is an acquired clonal disorder characterized by the polyagglutination of red blood cells by naturally occurring anti-Tn antibodies following exposure of the Tn antigen on the surface of erythrocytes. Only a subset of red cells express the antigen, which can also be expressed on platelets and leukocytes. This condition may occur in healthy individuals who manifest asymptomatic anemia, leukopenia, or thrombocytopenia; however, there is also an association between the Tn antigen and leukemia or myelodysplastic disorders. The Tn antigen is an incompletely glycosylated membrane glycoprotein with an exposed N-acetylgalactosamine residue. The Tn antigen results from inactivation of C1GALT1C1, which encodes a chaperone required for the correct functioning of T-synthetase (C1GALT1; 610555), an enzyme essential for the correct biosynthesis of O-glycans. Absence of active T-synthetase results in exposure of GalNAc residues, with a proportion of these residues becoming sialylated and forming a sialyl-Tn antigen (summary by Vainchenker et al., 1985 and Crew et al., 2008).
A condition in which the red blood cell level is greater than established reference ranges in a newborn.
A rare severe combined immunodeficiency disorder characterized by congenital agranulocytosis, lymphoid tissue and thymic tissue hypoplasia, and lymphopenia. Both cellular and humoral immunities are absent.
A rare, autosomal recessive disorder characterized by exocrine pancreas insufficiency, skeletal abnormalities, bone marrow dysfunction, and an increased incidence of leukemia.
Impaired egress of mature neutrophils from bone marrow causing neutropenia.
A type of agranulocytosis related to ingestion of a specific medication.
A rare autosomal recessive immunodeficiency disorder caused by deficiency of CD18 expression. It is characterized by defects in neutrophil adhesion and bacterial infections.
Familial eosinophilia is a rare autosomal dominant disorder characterized by peripheral hypereosinophilia (greater than 500 eosinophils/micro liter of blood) with or without other oragn involvement (summary by Rioux et al., 1998).
Familial hemophagocytic lymphohistiocytosis (FHL) is characterized by proliferation and infiltration of hyperactivated macrophages and T-lymphocytes manifesting as acute illness with prolonged fever, cytopenias, and hepatosplenomegaly. Onset is typically within the first months or years of life and, on occasion, in utero, although later childhood or adult onset is more common than previously suspected. Neurologic abnormalities may be present initially or may develop later; they may include increased intracranial pressure, irritability, neck stiffness, hypotonia, hypertonia, convulsions, cranial nerve palsies, ataxia, hemiplegia, quadriplegia, blindness, and coma. Rash and lymphadenopathy are less common. Other findings include liver dysfunction and bone marrow hemophagocytosis. The median survival of children with typical FHL, without treatment, is less than two months; progression of hemophagocytic lymphohistiocytosis and infection account for the majority of deaths in untreated individuals.
A localized tumor consisting of mature mast cells. (WHO, 2001) -- 2003
An indolent mast cell neoplasm characterized by systemic infiltration of skin and internal organs by aggregates of neoplastic mast cells. There is no evidence of mast cell leukemia or clonal hematologic malignancy. Clinically, there is no evidence of palpable hepatomegaly and splenomegaly, malabsorption syndrome, or pathologic fractures.
A rare inherited immunodeficiency syndrome characterized by normal or elevated serum IMMUNOGLOBULIN M levels with absence of IMMUNOGLOBULIN G; IMMUNOGLOBULIN A; and IMMUNOGLOBULIN E. It results in a profound susceptibility to BACTERIAL INFECTIONS and an increased susceptibility to OPPORTUNISTIC INFECTIONS. Several subtypes of hyper-IgM immunodeficiency syndrome exist depending upon the location of genetic mutation.
A rare, primary humoral immunodeficiency of childhood characterized by decreasing serum levels of immunoglobulin G (IgG) as maternal antibodies clear the circulation while serum levels of immunoglobulin A and immunoglobulin M remain normal or are slightly decreased. Diagnosis may be suspected after the age of six months when a child's own synthesis of IgG should accelerate but it must be confirmed retrospectively after normalization of all serum immunoglobulin levels is seen by ages 2-6. This disorder may be caused by inadequate activation of progenitor B cells, defective class-switching or may even represent a maturational variant. Typically, a normal response to protein antigens is found while there is a notably diminished response to viral and bacterial polysaccharide antigens. Clinical presentation may include recurrent infections especially those of the respiratory tract. Despite increased susceptibility to infection in childhood, this disorder is self-limited with minimal implications for a normal life span.
A broad classification for rare genetic disorders with mostly autosomal recessive patterns of inheritance. They are caused by the ineffective or decreased biosynthesis of complement components. Complement deficiencies may also be acquired acutely post-infection or chronically from co-morbid autoimmune disorders. If complement components are adequately synthesized, their rapid depletion may result in functional deficiencies. Clinical signs of inherited deficiencies present within the first decade of life and are consistent with the signs of recurrent systemic infection or immune complex disease. Complement deficiencies decrease the effectiveness of the humoral immune response. Of all the complement deficiencies, C3 deficiency is associated with the poorest prognosis since it presents at an early age, when susceptibility to recurrent infection is great. Deficiencies of C3 and of the classical activating pathway components: C1, C4, C2 also predispose to immune complex disease.
A primary disturbance in immunoglobulin synthesis characterized by the presence of two distinct monoclonal immunoglobulins in the serum or urine.
A localized, clonal (malignant) plasma cell infiltrate in the bone, without peripheral blood involvement. The most commonly affected bones are the vertebrae, ribs, skull, pelvis and femur. X-rays examination reveals a solitary lytic lesion.
A disorder of blood clotting that is attributable to a deficiency in liver function.
A life-threatening complication of heparin therapy. It results in immune-mediated thrombocytopenia and, in 25-50 percent of the patients, thrombotic complications.
A general class of thrombocytopenia due to immune destruction of platelets. It includes idiopathic thrombocytopenic purpura, as well as immune destruction-related thrombocytopenias due to other reasons (e.g., AIDS, transfusion, lupus erythematosus).
The gray platelet syndrome (GPS) is a rare inherited disorder characterized by mild to moderate bleeding tendency, moderate thrombocytopenia, and a marked decrease or absence of platelet alpha-granules and of the proteins contained in alpha-granules. The platelets are enlarged, but not giant, and have a gray appearance on light microscopy of Wright-stained peripheral blood smears due to decreased granules. Many patients with gray platelet syndrome develop a stable myelofibrosis (summary by Nurden and Nurden, 2007). Cases suggesting autosomal dominant and autosomal recessive inheritance have been described, indicating that GPS is probably a genetically heterogeneous disorder with more than one molecular cause.
Includes both quantitative and qualitative disorders of procoagulants
An inherited blood coagulation disorder characterized by deficiency of one of the coagulation factors, resulting in bleeding.
Prothrombin thrombophilia is an inherited disorder of blood clotting. Thrombophilia is an increased tendency to form abnormal blood clots in blood vessels. People who have prothrombin thrombophilia are at somewhat higher than average risk for a type of clot called a deep venous thrombosis, which typically occurs in the deep veins of the legs. Affected people also have an increased risk of developing a pulmonary embolism, which is a clot that travels through the bloodstream and lodges in the lungs. Most people with prothrombin thrombophilia never develop abnormal blood clots, however.Some research suggests that prothrombin thrombophilia is associated with a somewhat increased risk of pregnancy loss (miscarriage) and may also increase the risk of other complications during pregnancy. These complications may include pregnancy-induced high blood pressure (preeclampsia), slow fetal growth, and early separation of the placenta from the uterine wall (placental abruption). It is important to note, however, that most women with prothrombin thrombophilia have normal pregnancies.
A rare autosomal recessive inherited blood coagulation disorder characterized by deficiency of factor VII, resulting in bleeding.
Severe disease manifests factor VIII activity of less than 1%, except in the U.K. and Italy, where severe disease includes factor VIII activity levels of less than 2%
Moderate disease manifests factor VIII activity of 2% to 5% of normal
Mild disease manifests factor VIII activity of greater than 5% of normal
An acquired coagulation disorder characterized by the partial or complete absence of factor VIII activity in the blood.
A rare autosomal recessive inherited blood coagulation disorder characterized by deficiency of factor X, resulting in bleeding.
An acquired coagulation disorder characterized by the partial or complete absence of factor X activity in the blood.
A rare autosomal recessive inherited bleeding disorder caused by deficiency of coagulation factor XII. It may be asymptomatic or manifest with bleeding.
Prekallikrein deficiency is a blood condition that usually causes no health problems. In people with this condition, blood tests show a prolonged activated partial thromboplastin time (PTT), a result that is typically associated with bleeding problems; however, bleeding problems generally do not occur in prekallikrein deficiency. The condition is usually discovered when blood tests are done for other reasons.A few people with prekallikrein deficiency have experienced health problems related to blood clotting such as heart attack, stroke, a clot in the deep veins of the arms or legs (deep vein thrombosis), nosebleeds, or excessive bleeding after surgery. However, these are common problems in the general population, and most affected individuals have other risk factors for developing them, so it is unclear whether their occurrence is related to prekallikrein deficiency.
High molecular weight kininogen (HMWK) deficiency is an autosomal recessive coagulation defect. It is known by a variety of names, including Fitzgerald trait, Flaujeac trait, and Williams trait. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. Fitzgerald trait represents a 'true' deficiency of HMWK, whereas Flaujeac and Williams traits represent total kininogen deficiency, in which both HMWK and low molecular weight kininogen (LMWK) are deficient. HMWK and LMWK are both encoded by the KNG1 gene (612358) (Bick, 2002; Takagaki et al., 1985).
Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia; 202400) or the quality (dysfibrinogenemia) of the circulating fibrinogen, or both (hypodysfibrinogenemia). Patients with dysfibrinogenemia are frequently asymptomatic, but some patients have bleeding diathesis, thromboembolic complications, or both (summary by de Moerloose and Neerman-Arbez, 2009). Reports (e.g., Haverkate and Samama, 1995) on approximately 350 families with dysfibrinogenemia revealed that approximately half of cases are clinically silent, a quarter show a tendency toward bleeding, and another quarter show a predisposition for thrombosis with or without bleeding (summary by Lefebvre et al., 2004).
Deficiency of antithrombin III is a major risk factor for venous thromboembolic disease. Two categories of AT-III deficiency have been defined on the basis of AT-III antigen levels in the plasma of affected individuals. The majority of AT-III deficiency families belong in the type I (classic) deficiency group and have a quantitatively abnormal phenotype in which antigen and heparin cofactor levels are both reduced to about 50% of normal. The second category of AT-III deficiency has been termed type II (functional) deficiency. Affected individuals from these kindreds produce dysfunctional AT-III molecules; they have reduced heparin cofactor activity levels (about 50% of normal) but levels of AT-III antigen are often normal or nearly normal (summary by Bock and Prochownik, 1987). The 2 categories of antithrombmin III deficiency have been classified further. Type I (low functional and immunologic antithrombin) has been subdivided into subtype Ia (reduced levels of normal antithrombin), and type Ib (reduced levels of antithrombin and the presence of low levels of a variant). Type II (low functional but normal immunologic antithrombin) has been subdivided into subtype IIa (functional abnormalities affecting both the reactive site and the heparin-binding site of AT3); subtype IIb (functional abnormalities limited to the reactive site); and subtype IIc (functional abnormalities limited to the heparin-binding site) (summary by Lane et al., 1992).
Increase in size of the tonsils, small collections of lymphoid tissue facing into the aerodigestive tract on either side of the back part of the throat.
An abscess that develops in a lymph node and the surrounding tissues as a result of an infectious process. The affected lymph node is palpable and tender.
Regional lymph node enlargement with a distinctive reactive process that is characterized by paracortical hyperplasia composed of interdigitating dendritic cells, Langerhans cells, macrophages containing melanin pigment, and small T-cells, due to chronic inflammatory skin disease.
A circumscribed area of pus or necrotic debris in the parenchyma of the spleen.
A condition characterized by an abnormal spleen position due to loss, weakness, or malformation of one or more of the ligaments that hold the spleen in its normal position in the left upper abdomen. It may present as a birth defect or follow injuries or pregnancy. Signs and symptoms include abdominal discomfort and splenomegaly.
Chronic mountain sickness (CMS), or Monge disease, represents a state of maladaptation to high-altitude hypoxia in a member of a population acclimatized to high altitudes. CMS is characterized by severe polycythemia and an array of neurologic symptoms, including headache, fatigue, somnolence, and depression. Often, people with CMS suffer from strokes and myocardial infarctions in early adulthood because of increased blood viscosity. Studies have shown that CMS is common in Andeans, found occasionally in Tibetans, and absent from the Ethiopian population living on the East African high-altitude plateau (summary by Zhou et al., 2013). Acute mountain sickness (see pulmonary edema of mountaineers, 178400) is experienced by unacclimatized travelers exposed to high altitude.
Complications of BLOOD TRANSFUSION. Included adverse reactions are common allergic and febrile reactions; hemolytic (delayed and acute) reactions; and other non-hemolytic adverse reactions such as infections and adverse immune reactions related to immunocompatibility.
Transfusion reaction complications such as delayed suppression of ERYTHROPOIESIS may occur after destruction of autologous RED BLOOD CELLS in Hemolytic Transfusion Reaction.
Infection associated with no detectable symptoms but caused by microorganisms capable of producing easily recognizable diseases, such a poliomyelitis or mumps.
Simultaneous infection of a host organism by two or more pathogens. In virology, coinfection commonly refers to simultaneous infection of a single cell by two or more different viruses.
infections acquired in utero and persisting after birth; this term applies maninly to the infant, in contrast to PREGNANCY INFECTION, which applies mainly to the mother and fetus.
A bacterial infection by Listeria monocytogenes that is present at birth.
Latent syphilis when infection was acquired less than twelve months previously.
Tuberculosis of the brain, spinal cord, or meninges (TUBERCULOSIS, MENINGEAL), most often caused by MYCOBACTERIUM TUBERCULOSIS and rarely by MYCOBACTERIUM BOVIS. The infection may be limited to the nervous system or coexist in other organs (e.g., TUBERCULOSIS, PULMONARY). The organism tends to seed the meninges causing a diffuse meningitis and leads to the formation of TUBERCULOMA, which may occur within the brain, spinal cord, or perimeningeal spaces. Tuberculous involvement of the vertebral column (TUBERCULOSIS, SPINAL) may result in nerve root or spinal cord compression. (From Adams et al., Principles of Neurology, 6th ed, pp717-20)
Gastroenteritis resulting from an infection with Campylobacter.
Early yaws includes primary and secondary stages of yaws, endemic tropical treponemal nonvenereal infection: development of initial lesion at inoculation site followed by widespread dissemination of treponemes and generalized secondary granulomatous lesions that may relapse repeatedly.
Chronic endemic respiratory disease of dairy calves and an important component of bovine respiratory disease complex. It primarily affects calves up to six months of age and the etiology is multifactorial. Stress plus a primary viral infection is followed by a secondary bacterial infection. The latter is most commonly associated with PASTEURELLA MULTOCIDA producing a purulent BRONCHOPNEUMONIA. Sometimes present are MANNHEIMIA HAEMOLYTICA; HAEMOPHILUS SOMNUS and mycoplasma species.
A bacterial infection caused by Chlamydophila psittaci. Humans are infected by handling sick birds. The Chlamydiae cause respiratory infection manifests with fever, malaise, cough, dyspnea, sore throat, photophobia and headaches.
Myocarditis that is caused by an infection with a viral agent.
Pericarditis that is caused by an infection with a viral agent.
A viral disease infecting PRIMATES and RODENTS. Its clinical presentation in humans is similar to SMALLPOX including FEVER; HEADACHE; COUGH; and a painful RASH. It is caused by MONKEYPOX VIRUS and is usually transmitted to humans through BITES or via contact with an animal's BLOOD. Interhuman transmission is relatively low (significantly less than smallpox).
A serious viral disorder characterized by infection of the brain by herpes simplex virus type 1 or 2. Herpes simplex virus type 1 affects adults, whereas herpes simplex virus type 2 affects newborns. Signs and symptoms include fever, headaches, vomiting, seizures and psychiatric manifestations.
A herpesvirus infection of cattle characterized by catarrhal inflammation of the upper respiratory and alimentary epithelia, keratoconjunctivitis, encephalitis and lymph node enlargement. Syn: bovine epitheliosis, snotsiekte.
Pneumonia caused by cytomegalovirus. Most humans are exposed to cytomegalovirus. Healthy individuals do not develop signs and symptoms of infection. Patients with weakened immune system (e.g., AIDS patients, cancer patients who are being treated with chemotherapy, and patients who have received bone marrow or solid organ transplants) develop signs and symptoms of infection. They include cough, shortness of breath, fatigue, malaise, fever, muscle and joint pain, and excessive sweating.
A large penile lesion with indolent clinical course, composed of well-differentiated squamous cells. -- 2003
Virus infections caused by the PARVOVIRIDAE.
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is a cause of congenital brain abnormalities, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.
disease caused by strains of influenza A virus, causing influenza and pneumonia in domestic pigs.
An infectious process caused by rhinovirus. The virus usually causes upper respiratory infections, but can infect the lower tract as well.
A group of pathologic syndromes found in avian species caused by RETICULOENDOTHELIOSIS VIRUS. The distinct syndromes include non-neoplastic runting, acute neoplastic disease, and chronic neoplastic disease. Humans and mammals appear resistant.
The most aggressive form of Kaposi sarcoma. It presents in patients who are infected with the human immunodeficiency virus. It can affect the skin and internal organs.
Chronic hepatitis caused by viruses, most commonly hepatitis viruses B and C.
Pericarditis that is caused by an infection with a fungal agent.
Lung infections with the invasive forms of ASPERGILLUS, usually after surgery, transplantation, prolonged NEUTROPENIA or treatment with high-doses of CORTICOSTEROIDS. Invasive pulmonary aspergillosis can progress to CHRONIC NECROTIZING PULMONARY ASPERGILLOSIS or hematogenous spread to other organs.
A fungal infection by any of the Candida species in a newborn infant up to 28 days old.
Fungal pneumonia caused by inhalation of particles of Cryptococcus. It usually occurs in immunocompromised patients such as persons with AIDS, transplant recipients, patients receiving cytotoxic chemotherapy, and patients with hematologic malignancies. It is rare in immunocompetent individuals. Signs and symptoms include fever, cough, and dyspnea.
OPPORTUNISTIC INFECTIONS caused by the dematiaceous (darkly pigmented) MITOSPORIC FUNGI of ALTERNARIA, Bipolaris, CLADOSPORIUM, Curvularia, and EXOPHIALA. These fungi have pigmented HYPHAE due to MELANIN in the cell wall. The initial subcutaneous cyst from the infection can become systemic and spread rapidly to renal, pulmonary and cerebral systems (see CEREBRAL PHAEOHYPHOMYCOSIS) in an IMMUNOCOMPROMISED HOST.
An inflammatory manifestation of tinea capitis with a pronounced swelling that develops into suppurative central and indurated peripheral area called kerion.
OPPORTUNISTIC INFECTIONS with the soil fungus FUSARIUM. Typically the infection is limited to the nail plate (ONYCHOMYCOSIS). The infection can however become systemic especially in an IMMUNOCOMPROMISED HOST (e.g., NEUTROPENIA) and results in cutaneous and subcutaneous lesions, fever, KERATITIS, and pulmonary infections.
A granulomatous disease caused by the aquatic organism PYTHIUM insidiosum and occurring primarily in horses, cattle, dogs, cats, fishes, and rarely in humans. It is classified into three forms: ocular, cutaneous, and arterial.
A bladder infection that occurs as a manifetation of a systemic infection with one or more species of the parasitic worms of the Schistosoma type; this can progress to bladder cancer in time.
An infection caused by the parasite Opisthorchis viverrini. It results from the ingestion of raw or undercooked food. The clinical features vary from mild to severe and include gastrointestinal symptoms, anorexia, weight loss, hepatomegaly, and cholangitis. Patients are at an increased risk of developing cholangiocarcinoma.
An infection that is caused by the raccoon nematode Baylisascaris procyonis, which is transmitted by the ingestion of embryonated eggs in contaminated soil; symptoms depend on larval migration sites (visceral organs, eye, or brain) provoking severe inflammatory responses.
Bed bugs bite you and feed on your blood. You may have no reaction to the bites, or you may have small marks or itching. Severe allergic reactions are rare. Bed bugs don't transmit or spread diseases. Adult bed bugs are brown, 1/4 to 3/8 inch long, and have a flat, oval-shaped body. Young bed bugs (called nymphs) are smaller and lighter in color. Bed bugs hide in a variety of places around the bed. They might also hide in the seams of chairs and couches, between cushions, and in the folds of curtains. They come out to feed about every five to ten days. But they can survive over a year without feeding. To prevent bed bugs in your home:. -Check secondhand furniture for any signs of bed bugs before bringing it home. -Use a protective cover that encases mattresses and box springs. Check it regularly for holes. -Reduce clutter in your home so they have fewer places to hide. -Unpack directly into your washing machine after a trip and check your luggage carefully. When staying in hotels, put your suitcases on luggage racks instead of the floor. Check the mattress and headboard for signs of bed bugs. To get rid of bed bugs:. -Wash and dry bedding and clothing at high temperatures. -Use mattress, box spring, and pillow encasements to trap bed bugs and help detect infestations. -Use pesticides if needed. Environmental Protection Agency.
Parasitic attack by members of the order SIPHONAPTERA.
An infestation with the flea TUNGA PENETRANS causing inflammation, pruritus, and pain, in both humans and other mammals. There is a high incidence of secondary infections such as BACTEREMIA and TETANUS.
A viral or bacterial infectious process affecting the large intestine.
The constant presence of diseases or infectious agents within a given geographic area or population group. It may also refer to the usual prevalence of a given disease with such area or group. It includes holoendemic and hyperendemic diseases. A holoendemic disease is one for which a high prevalent level of infection begins early in life and affects most of the child population, leading to a state of equilibrium such that the adult population shows evidence of the disease much less commonly than do children (malaria in many communities is a holoendemic disease). A hyperendemic disease is one that is constantly present at a high incidence and/or prevalence rate and affects all groups equally. (Last, A Dictionary of Epidemiology, 3d ed, p53, 78, 80)
The return of a disease after a period of remission.
A disease that is confined to a specific organ or tissue and has not spread to other anatomic sites.
Hypersensitivity resulting in an adverse reaction upon exposure to a drug.
An indication that the subject's death was due to a mishap.
Removal of a dead body from the earth after burial.
Deranged function in an individual or an organ that is due to a disease. (MedicineNet.com)
A perceived attribute that is deeply discrediting and is considered to be a violation of social norms.
Extreme fatigue; inability to respond to stimuli.
Cycles of fever with intervening periods of normothermia.
The state or act of one who sits; the posture of one who occupies a seat.
Normally, the posterior and lateral fontanelles are obliterated by about six months after birth, the anterior fontanelle closes by about the middle of the second year. This term refers to the situation in which the fontanelles close at an inappropriately early time point.
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
WHAT: Tinel's sign. Tinel's Sign: a clinical test in which percussion of the median nerve at the volar aspect of the wrist produces a tingling sensation in the fingers supplied by the median nerve. WHY: The test helps in diagnosing those patients with carpal tunnel syndrome. HOW: The test is performed by lightly percussing the median nerve at the volar aspect of the wrist, just radial to the palmaris longus tendon. The test is considered positive if the patient experiences a tingling sensation in the thumb, index, middle or radial half of the ring finger or in the radial half of the palm. REFS: Phalen, GS: The carpal tunnel syndrome: seventeen years' experience in diagnosis and treatment of 654 hands. J Bone Joint Surg 48A:211, 1966. DN19301-1.
Enlargement of the nostrils during breathing; although there are many possible causes, it can be a sign of respiratory distress in young infants.
A mid-to-late diastolic murmur heard best at the cardiac apex, heard in cases of aortic insufficiency
High-pitched diastolic murmur heard best at left sternal border, associated with pulmonary valve insufficiency
A condition caused by one or more episodes of DEEP VEIN THROMBOSIS, usually the blood clots are lodged in the legs. Clinical features include EDEMA; PAIN; aching; heaviness; and MUSCLE CRAMP in the leg. When severe leg swelling leads to skin breakdown, it is called venous STASIS ULCER.
An erythematous (red), flat facial rash that affects the skin in the malar area (over the cheekbones) and extends over the bridge of the nose.
Hair that lacks the lustre (shine or gleam) of normal hair.
Air trapped in the subcutaneous space. It can be palpated or heard as a crackling or grating sensation under the skin.
A deviation from the normal odor of the urine.
A pregnancy that is complicated and affected by an abnormal finding or disease condition in either the fetus and/or the mother.
A change to an individual's judgment, orientation (to place, time, and self), intellectual functioning, or mood from their baseline.
Habitual, repeated, rapid contraction of certain muscles, resulting in stereotyped individualized actions that can be voluntarily suppressed for only brief periods. They often involve the face, vocal cords, neck, and less often the extremities. Examples include repetitive throat clearing, vocalizations, sniffing, pursing the lips, and excessive blinking. Tics tend to be aggravated by emotional stress. When frequent they may interfere with speech and INTERPERSONAL RELATIONS. Conditions which feature frequent and prominent tics as a primary manifestation of disease are referred to as TIC DISORDERS. (From Adams et al., Principles of Neurology, 6th ed, pp109-10)
A behavioral pattern characterized by a craving for the mood-altering effects of a drug and an overwhelming preoccupation with obtaining and using the drug.
The neuroadaptation of the body to the presence of an opioid, and is characterized by the onset of acute symptoms and signs of withdrawal if the opioid is stopped or an opioid antagonist is administered.
An involuntary, primal response in the neonate in which the arm extends to follow the infant's gaze, while the opposing arm and leg flex inward.
A pattern of sensory loss with selective loss of touch sensation and proprioception without loss of pain and temperature, or vice-versa.
Applied to pain that is dull, i.e., not severe but that continues over a long period of time.
An intense sensation of discomfort or distress that is sharp and feels as though a knife has penetrated an anatomical location.
An intense sensation of discomfort or distress that radiates from one location to another sharply.
Sudden, repetitive, nonrhythmic motor movements (spasms), involving the eyes and muscles of the face.
A segmental myoclonus of muscles innervated by the facial nerve. [HPO:probinson]
Outer genital organs are not visually male or female.
Ann Arbor Classification: Stage I: Involvement of a single lymph node region (I); or localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE) (rare in Hodgkin lymphoma).
Ann Arbor Classification: Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II); or localized involvement of a single extralymphatic organ or site in association with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm (IIE).
Ann Arbor Classification: Stage III: Involvement of lymph node regions on both sides of the diaphragm (III), which also may be accompanied by extralymphatic extension in association with adjacent lymph node involvement (IIIE) or by involvement of the spleen (IIIS) or both (IIIE,S).
Ann Arbor Classification: Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement; or isolated extralymphatic organ involvement in the absence of adjacent regional lymph node involvement, but in conjunction with disease in distant site(s); or any involvement of the liver or bone marrow, lungs (other than by direct extension from another site), or cerebrospinal fluid.
Stage II includes: IIA (T3, N0, M0); IIB (T4, N0, M0). T3: Tumor invades through the muscularis propria or into non-peritonealized pericolic or perirectal tissues. T4: Tumor directly invades other organs or structures, and/or perforates visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage III includes: IIIA (T1-T2, N1, M0); IIIB (T3-T4, N1, M0); IIIC (Any T, N2, M0). N1: Metastasis in 1 to 3 regional lymph nodes. N2: Metastasis in 4 or more regional lymph nodes. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage 1 includes T1, NO, MO. T1: Tumor 2.0 cm or less in greatest dimension. T1mic: Microinvasion 0.1 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th Ed.)-2003
Stage III is divided into two stages IIIA and IIIB. Stage IIIA includes: (T0, N2, M0); (T1, N2, M0); (T2, N2, M0); (T3, N1, M0); (T3, N2, M0). Stage IIIB includes: (T4, any N, M0). T4: Tumor of any size with direct extension to (a) chest wall or (b) skin. N2: Metastases in ipsilateral axillary lymph nodes fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis. N3: Metastasis in ipsilateral infraclavicular lymph nodes(s) with or without axillary lymph node involvement, or in clinically apparent ipsilateral internal mammary lymph node(s); and in the presence of clinically evident axillary lymph node metastasis or metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. M0: No distant metastasis. (AJCC 6th Ed.)
Stage IIIA includes: (T0, N2, M0); (T1, N2, M0); (T2, N2, M0); (T3, N1, M0); (T3, N2, M0). T0: No evidence of primary tumor. T1: Tumor 20 mm or less in greatest dimension. T1 includes T1mi. T1mi: Tumor 1 mm or less in greatest dimension. T2: Tumor more than 20 mm but not more than 50 mm in greatest dimension. T3: Tumor more than 50 mm in greatest dimension. N1: Metastasis to movable ipsilateral level I, II axillary lymph node(s). N2: Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted; or in clinically detected ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 7th Ed.)
The reemergence of carcinoma in the breast after a period of remission
Stage I includes: IA (T1, N0, M0); IB (T2, N0, M0); (T1, N1, M0). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: IIA (T3, N0, M0); (T2, N1, M0); (T1, N2, M0); IIB (T4a, N0, M0); (T3, N1, M0); (T2, N2, M0); (T1, N3, M0). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures. T4a: Tumor invades serosa (visceral peritoneum). N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: IIIA (T4a, N1, M0); (T3, N2, M0); (T2, N3, M0); IIIB (T4b, N0, M0); (T4b, N1, M0); (T4a, N2, M0); (T3, N3, M0); IIIC (T4b, N2, M0); (T4b, N3, M0); (T4a, N3, M0). T2: Tumor invades the muscularis propria. T3: Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures. T4a: Tumor invades serosa (visceral peritoneum). T4b: Tumor invades adjacent structures. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: (Any T, Any N, M1). M1: Distant metastasis. (AJCC 7th ed.)
The reemergence of gastric carcinoma after a period of remission.
Stage I includes: IA: (T1a, N0, M0); (T1b, N0, M0) and IB: (T2a, N0, M0). T1a: Lung cancer with a tumor size of 2 cm or less n greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a. T1b: Lung cancer with a tumor size more than 2 cm but 3 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). T2a: Lung cancer with a tumor size more than 3 cm but 5 cm or less in greatest dimension. N0: No regional lymph metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: IIA (T2b, N0, M0); (T1a, N1, M0); (T1b, N1, M0); (T2a, N1, M0) and IIB (T2b, N1, M0); (T3, N0, M0). T2b: Lung cancer with a tumor size more than 5 cm but 7 cm or less in greatest dimension. T1a: Lung cancer with a tumor size of 2 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a. T1b: Lung cancer with a tumor size more than 2 cm but 3 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). T2a: Lung cancer with a tumor size more than 3 cm but 5 cm or less in greatest dimension. T3: Lung cancer with a tumor size more than 7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumor in the main bronchus (less than 2 cm distal to the carina but without involvement of the carina); or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe. N0: No regional lymph node metastasis. N1: Lung cancer with metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary lymph nodes, including involvement by direct extension. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: IIIA (T1a, N2, M0); (T1b, N2, M0); (T2a, N2, M0); (T2b, N2, M0); (T3, N1, M0); (T3, N2, M0); (T4, N0, M0); (T4, N1, M0) and IIIB (T1a, N3, M0); (T1b, N3, M0); (T2a, N3, M0); (T2b, N3, M0); (T3, N3, M0); (T4, N2, M0); (T4, N3, M0). T4: Lung cancer with a tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodule(s) in a different ipsilateral lobe. N1: Lung cancer with metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary lymph nodes, including involvement by direct extension. N2: Lung cancer with metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes. N3: Lung cancer with metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
A medulloblastoma occurring in children.
An osteosarcoma which has spread to another anatomical site.
Stage IIIB includes: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0). T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules). N0: No regional lymph node metastasis. N1: Metastasis to movable ipsilateral level I, II axillary lymph node(s). N2: Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted; or in clinically detected ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 7th Ed.)
The re-emergence of non-small cell lung carcinoma after a period of remission.
The reemergence of acute lymphoblastic leukemia in childhood after a period of remission.
The reemergence of Hodgkin lymphoma in adulthood after a period of remission.
Stage II includes IIA (T3, N0, M0) and IIB (T4, N0, M0). T3: Tumor invades through the muscularis propria into the subserosa, or into nonperitonealized pericolic or perirectal tissues. T4: Tumor directly invades other organs or structures, and/or perforates the visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage III includes: IIIA (T1-T2, N0, M0); IIIB (T3-T4, N1, M0); IIIC (Any T, N2, M0). N1: Metastasis in 1 to 3 regional lymph nodes. N2: Metastasis in 4 or more regional lymph nodes. (AJCC 6th ed.) - 2003
The reemergence of colon carcinoma after a period of remission.
The reemergence of rectal carcinoma after a period of remission.
The reemergence of anal carcinoma after a period of remission.
Stage I includes: T1, N0, M0. TI: Tumor invades lamina propria or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) -2003
Stage II includes: IIA: (T2, N0, M0); (T3, N0, M0) and IIB: (TI, NI, M0); (T2, NI, M0). TI: Tumor invades lamina propria or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) -2003
Stage III includes: T3, N1, M0 and T4, Any N, M0) T3: Tumor invades adventitia. T4: Tumor invades adjacent structures. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) -2003
Stage IV includes: For squamous cell carcinoma: Any T, Any N, M1, Any G, Tumor location: Any. For adenocarcinoma: Any T, Any N, M1, Any G. M1: Distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
May be either of the following: (1) stage IA cancer affecting less than 10% of the skin's surface and appearing as red, dry, scaly patches; (2) stage IB cancer affecting 10% or more of the skin's surface and appearing as red, dry, scaly patches.
Stage I includes: IA (T1, N0, M0, B0-1); IB (T2, N0, M0, B0-1). T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque +/- patch). T2: Patches, papules, or plaques covering 10% or more of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque +/- patch). N0: No clinically abnormal peripheral lymph nodes; biopsy not required. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 7th ed.)
Stage II cutaneous T-cell lymphoma may be either of the following: (1) stage IIA, in which the skin has red, dry, scaly patches but no tumors, and lymph nodes are enlarged but do not contain cancer cells; (2) stage IIB, in which tumors are found on the skin, and lymph nodes are enlarged but do not contain cancer cells.
Stage II includes: IIA (T1-2, N1-2, M0, B0-1); IIB (T3, N0-2, M0, B0-1). T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque +/- patch). T2: Patches, papules, or plaques covering 10% or more of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque +/- patch). T3: One or more tumors (equal or greater than 1 cm diameter). N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 7th ed.)
Nearly all of the skin is red, dry, and scaly; lymph nodes are either normal or enlarged but do not contain cancer cells.
Stage III includes: (T4, N0-2, M0, B0-1); IIIA (T4, N0-2, M0, B0); IIIB (T4, N0-2, M0, B1). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 7th ed.)
Stage IV cutaneous T-cell lymphoma may be either of the following: in stage IVA cancer, the skin is red, dry, and scaly, and the lymph nodes contain cancer cells; in stage IVB cancer, the skin is red, dry and scaly, cancer cells may be found in lymph nodes, and cancer has spread to other organs in the body.
Stage IV includes: IVA1 (T1-4, N0-2, M0, B2); IVA2 (T1-4, N3, M0, B0-2); IVB (T1-4, N0-3, M1, B0-2). T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque +/- patch). T2: Patches, papules, or plaques covering 10% or more of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque +/- patch). T3: One or more tumors (equal or greater than 1 cm diameter). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. M0: No visceral organ involvement. M1: Visceral involvement (must have pathology confirmation and organ involved should be specified). B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. B2: High blood tumor burden: 1000/microL Sezary cells or more with positive clone. (AJCC 7th ed.)
Stage IV includes: IVA: (T4, Any N, M0); IVB (Any T, Any N, MI). T4: Tumor invades mucosa of bladder or rectum, and/or extends beyond true pelvis (bullous edema is not sufficient to classify a tumor as T4). M1: Distant metastasis. (AJCC 6th and 7th eds.)
The reemergence of cervical carcinoma after a period of remission.
A carcinoma that has spread to the cervix from another anatomic site.
Ewing sarcoma which has spread from its original site of growth to another anatomic site.
Ewing sarcoma which has recurred after treatment and/or remission. While initial complete responses are not uncommon, there is a fair chance of relapse as late as one to two decades after initial therapy.
An angiosarcoma occurring in the adult population.
Benign and malignant astrocytomas that arise from astrocytes in the cerebellum. More than 80% of childhood cerebellar astrocytomas are pilocytic astrocytomas which have a favorable prognosis. The remainder are composed of diffuse or fibrillary subtypes with malignant astrocytomas occurring only rarely in the cerebellum during childhood.
A malignant mesenchymal neoplasm composed of fibroblasts. It is characterized by collagen production and a herringbone architectural pattern. It is more commonly seen in middle-aged and older adults. It usually affects the deep soft tissues of extremities, trunk, head and neck. Adult fibrosarcomas may recur and metastasize to the lungs and bones.
An ependymoma that arises from the infratentorial region of the brain and occurs during childhood.
An abnormal growth of the cells that comprise the tissues of the brainstem. While the tumor may be histologically benign, it can produce great morbidity due to its location. It presents most commonly in the first two decades of life.
An advanced, invasive breast adenocarcinoma characterized by the presence of distinct changes in the overlying skin. These changes include diffuse erythema, edema, peau d'orange (skin of an orange) appearance, tenderness, induration, warmth, enlargement, and in some cases a palpable mass. The skin changes are the consequence of lymphatic obstruction from the underlying invasive breast adenocarcinoma. Microscopically, the dermal lymphatics show prominent infiltration by malignant cells. The invasive breast adenocarcinoma is usually of ductal, NOS type. There is not significant inflammatory cell infiltrate present, despite the name of this carcinoma.
An aggressive malignant smooth muscle neoplasm, occurring in adults. It is characterized by a proliferation of neoplastic spindle cells.
A malignant neoplasm arising from adipocytes, that occurs in adults. The tumor maybe one of several histologic types including well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic liposarcoma.
A plasma cell neoplasm arising at an extraosseous site. There is no involvement of the bone marrow. It most frequently involves the oropharynx, nasopharynx, sinuses, and larynx. Other sites of involvement include the gastrointestinal tract, central nervous system, breast, skin, lymph nodes, and bladder. A minority of patients have a monoclonal gammopathy. Treatment includes radiation therapy. Progression to plasma cell myeloma occurs in a minority of patients.
A plasma cell neoplasm that is resistant to treatment.
A malignant peripheral nerve sheath tumor occurring during adulthood.
The reemergence of childhood rhabdomyosarcoma after a period of remission.
An ependymoma that arises from the supratentorial region of the brain and occurs during childhood.
A craniopharyngioma that occurs during childhood. The vast majority of cases are adamantinomatous craniopharyngiomas. Clinical signs and symptoms include endocrine deficiencies and visual disturbances.
A glioma affecting the optic tract and occurring in childhood.
Stage I includes: T1, N0, M0. T1: Lesions have been divided into T1a and T1b. T1a is defined as tumor 4 cm or less in greatest dimension, limited to the kidney. T1b is defined as tumor greater than 4 cm but not more than 7 cm in greatest dimension, limited to the kidney. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage II includes: T2, N0, M0. T2: Tumor more than 7 cm in greatest dimension limited to the kidney. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 6th Ed.) - 2003
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, N0, M0); (T3, N1, M0); (T3a, N0, M0); (T3a, N1, M0); (T3b, N0, M0); (T3b, N1, M0); (T3c, N0, M0); (T3c, N1, M0). T3: Tumor extends into major veins or invades adrenal gland or perinephric tissues but not beyond Gerota's fascia. T3a: Tumor directly invades adrenal gland or perirenal and/or renal sinus fat but not beyond Gerota's fascia. T3b: Tumor grossly extends into the renal vein or its segmental (muscle containing) branches, or vena cava below the diaphragm. T3c: Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava. N0: No regional lymph node metastases. N1: Metastasis in a single regional lymph node. M0: No distant metastasis. (AJCC 6th Ed.) - 2003
A renal cell cancer that has invaded the renal capsule and has spread to lymph nodes and other anatomic sites. Metastatic renal cell cancer is stage IV, but stage IV includes some non-metastatic tumors, e.g. T4 M0. --2003
A reemergence of renal cell carcinoma after a period of remission.
A parathyroid gland carcinoma that has not spread to other anatomic sites.
A parathyroid gland carcinoma that has spread to other anatomic sites.
The reemergence of parathyroid gland carcinoma after a period of remission.
Stage I includes: T1, N0, M0. T1: Tumor limited to ovaries (one or both). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage II includes: T2, N0, M0. T2: Tumor involves one or both ovaries with pelvic extension and/or implants. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage III includes: T3, N0, M0. T3: Tumor involves one or both ovaries with microscopically confirmed peritoneal metastasis outside pelvis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis (excludes peritoneal metastasis). (AJCC 6th and 7th eds.)
The reemergence of ovarian carcinoma after a period of remission.
The reemergence of brain neoplasm in childhood after a period of remission.
A neuroblastoma which is confined to a specific site and is amenable to surgical removal.
A neuroblastoma confined to a specific anatomic region without evidence of dissemination.
Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin, and/or other organs, except as defined for stage 4S. (cancer.gov)
The reemergence of neuroblastoma after a period of remission.
Stage III includes: IIIA: (T3a, N0, M0); IIIB: (T3b, N0, M0); IIIC: (T4, N0, M0). T3a: Multiple tumors more than 5 cm. T3b: Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein. T4: Tumors(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
A hepatocellular carcinoma or hepatoblastoma that occurs during childhood and has recurred after a period of remission.
An adenocarcinoma arising from the stomach glandular epithelium. Gastric adenocarcinoma is primarily a disease of older individuals. It most commonly develops after a long period of atrophic gastritis and is strongly associated with Helicobacter pylori infection. The lack of early symptoms often delays the diagnosis of gastric cancer. The majority of patients present with advanced tumors which have poor rates of curability. Microscopically, two important histologic types of gastric adenocarcinoma are recognized: the intestinal and diffuse type. The overall prognosis of gastric adenocarcinomas is poor, even in patients who receive a ""curative"" resection (adapted from Sternberg's Surgical Pathology, 3rd ed., 1999).
A malignant tumor that occurs in children. Representative examples include soft tissue and bone sarcomas (e.g. osteosarcoma) and embryonal neoplasms (e.g. hepatoblastoma and rhabdoid tumor).
The tumor was completely removed by surgery and all of the following are true: (1) cancer was found only in the kidney and did not spread to blood vessels of the kidney; (2) the outer layer of the kidney did not break open; (3) the tumor did not break open; (4) a biopsy of the tumor was not done; and (5) no cancer cells were found at the edges of the area where the tumor was removed.
Cancer spread out of the kidney to nearby soft tissue or to blood vessels of the kidney and was completely removed by surgery. No cancer cells were found at the edges of the area where the cancer was removed.
Cancer remains in the abdomen after surgery and at least one of the following is true: (1) cancer has spread to lymph nodes in the abdomen or pelvis (the part of the body between the hips); (2) cancer has spread to or through the surface of the peritoneum (the layer of tissue that lines the abdominal cavity and covers most organs in the abdomen); (3) a biopsy of the tumor was done during surgery to remove it; (4) the tumor was removed in more than one piece.
Cancer has spread through the blood to organs such as the lungs, liver, bone, or brain, or to lymph nodes outside of the abdomen and pelvis (the part of the body between the hips).
Cancer cells are found in both kidneys when the disease is first diagnosed. Each kidney is staged separately as I, II, III, or IV.
The reemergence of Wilms tumor of the kidney after a period of remission.
Retinoblastoma restricted to local involvement.
Risk: Low; Findings: Lymphocytosis only; Survival (months): more than 120. (from AJCC 8th Ed.)
Retinoblastoma that has spread beyond the eye e.g. to brain, soft tissue/bone, bone marrow.
A lymphoblastic lymphoma occurring in adults.
Plasma cell myeloma with all of the following: 1. Hemoglobin greater than 10 g/Dl, 2. Normal serum calcium, 3. Normal bone structure, 4. Low monoclonal (or myeloma) protein (M protein) production as shown by: a. IgG less than 5.0 g/dL, b. IgA less than 3.0 g/dL, c. Urinary kappa or lamda less than 4 g/24 hours. Estimated myeloma cell mass: less than 0.6 trillion (1012)/m2 (low burden). The following subclassification of stages is used: a. Creatinine less than 2.0 mg/dL, b. Creatinine greater than or equal to 2.0 mg/dL. Impaired renal function worsens prognosis regardless of stage. Note that the newer International Staging System defines stage I quite differently: Beta-2-microglobulin less than 3.5 and albumin greater than or equal to 3.5 (median survival of 62 months). (PDQ)
Plasma cell myeloma that fits in neither stage I nor stage III. Estimated myeloma cell mass: 0.6 to 1.2 trillion (1012)/m2 (intermediate burden). The following subclassification of stages is used: a. Creatinine less than 2.0 mg/dL, b. Creatinine greater than or equal to 2.0 mg/dL. Impaired renal function worsens prognosis regardless of stage. Note that the newer International Staging System defines stage II quite differently: Beta-2-microglobulin less than 3.5 and albumin less than 3.5 or beta-2-microglobulin 3.5 to less than 5.5 (median survival of 44 months). (PDQ)
Plasma cell myeloma with one or more of the following: 1. Hemoglobin less than 8.5 g/dL. 2. Serum calcium greater than 12.0 mg/dL. 3. More than three lytic bone lesions. 4. High M protein production as shown by: a. IgG greater than 7.0 g/dL. b. IgA greater than 5.0 g/dL. c. Urinary kappa or lamda greater than 12.0 g/24 hours. Estimated myeloma cell mass: greater than 1.2 trillion (1012)/m2 (high burden). The following subclassification of stages is used: a. Creatinine less than 2.0 mg/dL. b. Creatinine greater than or equal to 2.0 mg/dL. Serum beta-2-microglobulin has been shown to be a reliable marker for prognosis. Since the great majority of symptomatic myeloma patients are classified as stage III by the Durie/Salmon criteria, this staging system has not proven to be very useful for identifying the patients with intermediate and poor prognosis. Note that the newer International Staging System defines stage III quite differently: Beta-2-microglobulin greater than or equal to 5.5 (median survival of 29 months). (PDQ)
Small cell lung carcinoma which is confined to one hemi-thorax and the regional lymph nodes.
Small cell lung carcinoma which has spread beyond one hemi-thorax and the regional lymph nodes.
The reemergence of small cell carcinoma of the lung after a period of remission.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ (preinvasive carcinoma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage IV includes: IVA (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4, Any N, M0); IVB (Any T, Any N, M1). T4: Tumor invades any of the following: upper urethra bladder mucosa, rectal mucosa, or is fixed to the pubic bone. N2: Bilateral regional lymph node metastasis. M1: distant metastasis (including pelvic lymph node metastasis). (AJCC 6th ed.) - 2003
The reemergence of vulvar carcinoma after a period of remission.
Stage I: A single tumor or nodal area is involved, excluding the abdomen and mediastinum (from PDQ).
Stage II: Disease extent is limited to a single tumor with regional node involvement, 2 or more tumors or nodal areas involved on one side of the diaphragm, or a primary gastrointestinal tract tumor (completely resected) with or without regional node involvement (from PDQ).
Stage III: Tumors or involved lymph node areas occur on both sides of the diaphragm. Stage III also includes any primary intrathoracic (mediastinal, pleural, or thymic) disease, extensive primary intra-abdominal disease, or any paraspinal or epidural tumors (from PDQ).
Stage IV: Tumors involve bone marrow and/or central nervous system (CNS) regardless of other sites of involvement (from PDQ).
The reemergence of lymphoblastic lymphoma in childhood after a period of remission.
The reemergence of vaginal carcinoma after a period of remission.
A well differentiated neuroendocrine tumor (carcinoid tumor) that arises from the digestive system and is restricted to the site of origin without evidence of metastasis.
A well differentiated neuroendocrine tumor (carcinoid tumor) that arises from the digestive system and has spread into adjacent tissues and regional lymph nodes.
A well differentiated neuroendocrine tumor (carcinoid tumor) that arises from the digestive system and has reemerged after a period of remission.
A malignant mesothelioma that has not spread beyond its original site of growth.
A malignant mesothelioma that has spread beyond its original site of growth.
The reemergence of malignant mesothelioma after a period of remission
A germ cell tumor of the central nervous system occurring in children.
A B-or T-cell non-Hodgkin lymphoma composed of a mixed-sized lymphocytic population occurring in adults.
A B-or T-cell non-Hodgkin lymphoma composed of a diffuse large cell lymphocytic infiltrate occurring in adults.
A morphologic variant of diffuse large B-cell lymphoma occurring in adults. It is characterized by the presence of large lymphoid cells with abundant cytoplasm and prominent nucleoli.
The sodium form of allopurinol, which is a structural isomer of hypoxanthine. Allopurinol inhibits xanthine oxidase, an enzyme that converts oxypurines to uric acid. By blocking the production of uric acid, this agent decreases serum and urine concentrations of uric acid, thereby providing protection against uric acid-mediated end organ damage in conditions associated with excessive production of uric acid, i.e. the massive cell lysis associated with the treatment of some malignancies. (NCI04)
Risk: Intermediate; Findings: Lymphocytosis and adenopathy; Survival (months): 95. (from AJCC 8th Ed.)
Risk: High; Findings: Lymphocytosis and hemoglobin less than 11 g/dL; Survival (months): 30. (from AJCC 8th Ed.)
A localized hepatocellular carcinoma or intrahepatic cholangiocarcinoma that occurs during adulthood and it is amenable to surgical resection.
A localized hepatocellular carcinoma or intrahepatic cholangiocarcinoma that occurs during adulthood and it is not amenable to surgical resection.
A hepatocellular carcinoma or intrahepatic cholangiocarcinoma that occurs during adulthood and has recurred after a period of remission.
The reemergence of acute myeloid leukemia in childhood after a period of remission.
The reemergence of osteosarcoma after a period of remission.
The reemergence of acute myeloid leukemia in adults after a period of remission.
The reemergence of acute lymphoblastic leukemia in adults after a period of remission.
The reemergence of chronic myelogenous leukemia after a period of remission.
Chronic lymphocytic leukemia that is resistant to treatment.
The reemergence of gestational trophoblastic tumor after a period of remission.
Reemerging uterine corpus carcinoma after a period of remission.
A malignant epithelial tumor with a glandular organization that originates in the small intestine.
A malignant epithelial tumor with a glandular organization that originates in the duodenum.
A non-Hodgkin or Hodgkin lymphoma that arises from the small intestine.
A malignant neoplasm that arises from the gallbladder and it has not spread to other anatomic sites.
A carcinoma that arises from the gallbladder and it is not amenable to surgical resection.
A carcinoma that arises from the extrahepatic bile ducts and it has not spread to other anatomic sites.
Extrahepatic bile duct carcinoma that is not amenable to surgical removal.
The reemergence of an extrahepatic bile duct carcinoma after a period of remission.
The reemergence of adrenal cortex carcinoma after a period of remission.
Stage 0 includes: 0a (Ta, N0, M0); 0is (Tis, N0, M0). Ta: Noninvasive papillary carcinoma. Tis: Carcinoma in situ: ""flat tumor"". N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage I includes: T1, N0, M0. T1: Tumor invades subepithelial connective tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage II includes: (T2a, N0, M0); (T2b, N0, M0). T2a: Tumor invades superficial muscle (inner half). T2b: Tumor invades deep muscle (outer half). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage III includes: (T3a, N0, M0); (T3b, N0, M0); (T4a, N0, M0). T3a: Tumor microscopically invades perivesical tissue. T3b: Tumor macroscopically invades perivesical tissue (extravesical mass). T4a: Tumor invades prostatic stroma, uterus, vagina. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
The reemergence of bladder carcinoma after a period of remission.
Stage IV includes the following: T4b, N0, M0; Any T, N1, M0; Any T, N2 M0; Any T, N3 M0; Any T, Any N, M1. T4b: Tumor invades the pelvic wall, abdominal wall. N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension. N2: Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension. N3: Metastasis in a lymph node more than 5 cm in greatest dimension. M1: Distant metastasis. (AJCC 6th Ed.) - 2003
Stage I includes: T1, N0, M0, G1. T1: Tumor invades subepithelial connective tissue. N0: No regional metastasis. M0: No distant metastasis. G1: Well differentiated (slight anaplasia) (Gleason 2-4). (AJCC 6th ed.) - 2003
Stage II includes: (T1a, N0, M0, G2, 3-4); (T1b, N0, M0, Any G); (T1c, N0, M0, Any G); (T1, N0, M0, Any G); (T2, N0, M0, Any G). T1: Clinically inapparent tumor neither palpable nor visible by imaging. T1a: Tumor incidental histologic finding in 5% of tissue resected. T1c: Tumor identified by needle biopsy (e.g. because of elevated PSA). T2: Tumor confined with in the prostate. N0: No regional lymph node metastasis. M0: No distant metastasis. G2: Moderately differentiated (moderate anaplasia) (Gleason 5-6). G 3-4: Poorly differentiated/undifferentiated (marked anaplasia) (Gleason 7-10). (AJCC 6th ed.) - 2003
Stage III includes: T3, N0, M0, Any G. T3: Tumor extends through the prostatic capsule. T3a: Extracapsular extension (unilateral or bilateral). T3b: Tumor invades seminal vesicle(s). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage IV includes: (T4, N0, M0); (Any T, N1, M0); (Any T, Any N, M1) (Any G). T4: Tumor is fixed or invades adjacent structures other than seminal vesicles: bladder neck, external sphincter, rectum, levator muscles, and/or pelvic wall. N1: Metastasis in regional lymph node(s). M1: Distant metastasis. (AJCC 6th ed.) - 2003
Prostate carcinoma reemerging after a period of remission.
A diffuse large cell lymphoma occurring in children.
Malignant testicular germ cell tumor reemerging after a period of remission.
An immunoblastic lymphoma (a variant of diffuse large B-cell lymphoma) occurring in children.
A malignant thymoma that extends beyond the capsule and infiltrates the surrounding tissues.
A morphologically malignant thymoma that is entirely confined within the capsule.
Reemergence of malignant thymoma after a period of remission.
Stage I includes: Under 45 years: Any T, Any N, M0. 45 years and older: T1, N0, M0. T1: Tumor size 2 cm or less in greatest dimension, limited to the thyroid gland. N0: No regional lymph node metastasis. M0: No evidence of distant metastasis. (from AJCC 7th Ed.)
Stage II includes: Under 45 years: Any T, Any N, M1. 45 years and older: T2, N0, M0. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid gland. N0: No regional lymph node metastasis. M1: Distant metastasis. M0: No evidence of distant metastasis. (from AJCC 7th Ed.)
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1a, M0); (T1, N1b, M0); (T2, N1b, M0); (T3, N1b, M0); (T4a, N1b, M0); IVB (T4b, Any N, M0); IVC (Any T, Any N, M1). T4a: Moderately advanced local disease. Tumor of any size extending beyond the thyroid gland capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve. T1: Tumor size 2 cm or less in greatest dimension, limited to the thyroid gland. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid gland. T3: Tumor more than 4 cm in greatest dimension and limited to the thyroid gland, or tumor of any size with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues). T4b: Very advanced disease. Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels. N0: No regional lymph node metastasis. N1a: Metastasis to pretracheal, paratracheal or prelaryngeal/Delphian lymph nodes (Level VI lymph nodes). N1b: Metastasis to unilateral, bilateral or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII). M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
A morphologic variant of undifferentiated (anaplastic) carcinoma of the thyroid gland, characterized by the presence of large numbers of non-neoplastic, osteoclast-like giant cells.
The reemergence of a thyroid gland carcinoma after a period of remission.
An adenoma or carcinoma of the pituitary gland that produces corticotropin.
An adenoma or carcinoma of the anterior lobe of the pituitary gland that produces prolactin.
An adenoma or carcinoma of the anterior lobe of the pituitary gland that produces growth hormone.
A craniopharyngioma that occurs during adulthood. It can be either adamantinomatous or papillary. The papillary histologic variant occurs virtually exclusively in adults. Clinical signs and symptoms include visual disturbances and endocrine deficiencies.
A meningioma that occurs during adulthood.
A Burkitt lymphoma occurring in children.
Stage I includes: IA (T1a, N0, M0); IB (T1b, N0, M0); (T2a, N0, M0). T1a: Melanoma is less than or equal to 1.0mm in thickness with or without ulceration. T1b: Melanoma is less than or equal to 1.0mm in thickness and level IV or V with ulceration. T2a: Melanoma 1.01-2.0 mm in thickness, no ulceration. N0: No regional lymph node metastasis. M0: No distant metastasis.-2003
Stage III includes: (Any T, N1, M0); (Any T, N2, M0); (Any T, N3, M0). N1: Metastasis in one lymph node. N2: Metastasis in two to three regional lymph nodes or intralymphatic regional metastasis without nodal metastases. N3: Metastasis in four or more regional nodes, or matted metastatic nodes, or in-transit metastasis or satellite(s) with metastasis in regional node(s). - 2003
A melanoma that has spread from its primary site to another anatomic site. Melanomas frequently metastasize to lymph nodes, liver, lungs, and brain.
Previous biologic therapy administered as treatment.
The reemergence of nasopharyngeal carcinoma after a period of remission.
An event in a personal medical history indicating that a myocardial infartion has occurred during the previous 6 months.
The two most severe classes of cardiac dysfunction according to a classification system developed by the New York Heart Association to grade cardiovascular function and disability. These classes are defined as follows: Class III - patients with cardiac disease producing marked limitation of activity: comfortable at rest. Less than ordinary physical activity causes symptoms. Class IV - patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms may be present even at rest.
Stage IIIA includes: (T1a, N2, M0); (T1b, N2, M0); (T2a, N2, M0); (T2b, N2, M0); (T3, N1, M0); (T3, N2, M0); (T4, N0, M0); (T4, N1, M0). T4: Lung cancer with a tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodule(s) in a different ipsilateral lobe. N1: Lung cancer with metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary lymph nodes, including involvement by direct extension. N2: Lung cancer with metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: (T1a, N3, M0); (T1b, N3, M0); (T2a, N3, M0); (T2b, N3, M0); (T3, N3, M0); (T4, N2, M0); (T4, N3, M0). T4: Lung cancer with a tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodule(s) in a different ipsilateral lobe. N2: Lung cancer with metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes. N3: Lung cancer with metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
An osteosarcoma arising from the soft tissue, and occurring in adults.
Stage IV includes: (Any T, Any N, M1a); (Any T, Any N, M1b). M1a: Lung cancer with separate tumor nodule(s) in a contralateral lobe; tumor with pleural nodules or malignant pleural (or pericardial) effusion. M1b: Distant metastasis. (AJCC 7th ed.)
The reemergence of salivary gland carcinoma after a period of remission.
A primary or metastatic malignant neoplasm affecting the head and neck. Representative examples include oral cavity squamous cell carcinoma, laryngeal squamous cell carcinoma, and salivary gland carcinoma.
A carcinoma that arises from the hepatocytes or intrahepatic bile ducts. The main subtypes are hepatocellular carcinoma (hepatoma) and cholangiocarcinoma.
A germ cell tumor that occurs during childhood.
A vaccine made of cancer cells, parts of cancer cells, or pure tumor antigens (substances isolated from tumor cells). A tumor antigen vaccine may stimulate the body's immune system to find and kill cancer cells.
Lymphomatoid granulomatosis characterized by the presence of a polymorphous lymphoid infiltrate without cytologic atypia. Large lymphocytes are absent or rare. By in situ hybridization, EBV-positive cells are infrequently seen.
Lymphomatoid granulomatosis characterized by the presence of aggregates of neoplastic large B-lymphocytes, usually admixed with pleomorphic and Hodgkin-like cells, in a background of chronic inflammation. Necrotic changes are present and are usually extensive. Grade III lymphomatoid granulomatosis should be approached clinically as a subtype of diffuse large B-cell lymphoma.
A solid neoplasm (e.g., carcinoma, sarcoma) occurring in children.
An oligodendroglioma occurring during adulthood.
A recombinant human soluble CD4 with antiviral activity. Recombinant human soluble CD4 has the amino terminus but not the T-cell binding domain of the endogenous CD4 antigen. This soluble CD4 protein competitively binds to envelope glycoprotein (gp120) of human immunodeficiency virus (HIV) resulting in inhibition of interaction between gp120 and the endogenous CD4 antigen, thereby blocking viral recognition of CD4 and subsequent entry of HIV into CD4 bearing cells.
Infiltration of the meninges by chronic myelogenous leukemia, BCR-ABL1 positive.
A vascular sarcoma that commonly occurs in the lower extremities. It occurs predominantly in elderly male patients of southern European ancestry. It is characterized by the presence of purple, red-blue, or dark brown macular lesions, plaques and nodules. This disease is usually slow growing, although it can spread to the lungs and the gastrointestinal tract. If necessary, cutaneous lesions can be treated with radiation.
A Kaposi sarcoma that develops after immunosuppressive treatment.
The reemergence of Kaposi sarcoma after a period of remission.
A finding of acute lymphoblastic leukemia in adulthood that has not been treated.
A finding of acute myeloid leukemia in adulthood that has not been treated.
A finding of acute lymphoblastic leukemia in childhood that has not been treated.
Acute myeloid leukemia in adults which is not growing and responds to treatment.
Acute lymphoblastic leukemia in adults which is not growing and responds to treatment.
Acute myeloid leukemia of childhood which is not growing and responds to treatment.
Acute lymphoblastic leukemia in children which is not growing and responds to treatment.
An indicator that a person has been previously received radiation treatment for the same condition.
A steroidal alkylating agent with potential antineoplastic activity. Alkylating agents exert cytotoxic and, in some cases, chemotherapeutic effects by transferring alkyl groups to DNA, thereby damaging DNA and interfering with DNA replication and cell division. (NCI04)
An oil based formulation of Vasopressin, which could be administered intramuscularly. (NCI)
Recombinant forms of the naturally occurring hormones synthesized by the pituitary gland.
Stage III includes: (T3, N0, M0); (T1, N1a, M0); (T2, N1a, M0); (T3, N1a, M0). T3: Tumor greater than 4 cm in greatest dimension and limited to the thyroid gland, or tumor of any size with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues). T1: Tumor size 2 cm or less in greatest dimension, limited to the thyroid gland. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid gland. N0: No regional lymph node metastasis. N1a: Metastasis to pretracheal, paratracheal or prelaryngeal/Delphian lymph nodes (Level VI lymph nodes). M0: No distant metastasis. (AJCC 7th ed.)
A murine monoclonal IgG2a antibody to tumor-associated epithelial cell adhesion molecule (EpCAM, or 17-1A) antigen. Edrecolomab attaches to EpCAM, a human cell surface glycoprotein that is found on normal epithelial cells and some tumor cells, such as those of colon and breast carcinomas. Upon binding, this agent recruits the body's immune effector cells, which may exhibit antitumor cytotoxicity. (NCI04)
An IgG murine monoclonal antibody directed against the ganglioside GD3 glycolipid, located in the cell membranes of some tumor cells. Monoclonal antibody R24 binds to GD3-positive cells, thereby initiating antibody-dependent cytotoxicity against GD3-positive cells. (NCI04)
A naturally occurring mucin glycoprotein. Ovine submaxillary mucin (OSM), extracted from an ovine submaxillary gland, provides a rich source of the sialylated Tn antigen (sTn), which is a carbohydrate antigen found on mucins of many epithelial tumors. Vaccination with OSM may result in the production of antibodies as well as elicitation of a cytotoxic T- lymphocyte (CTL) response against tumor cells expressing sTn, thereby results in decreased tumor cell growth.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Oxygen that is administered at a higher pressure compared to standard (i.e. sea-level) atmospheric pressure. Administration of oxygen under hyperbaric conditions enhances the delivery of oxygen to hypoxic tumor cells, thereby increasing their sensitivity to radiation and chemotherapy. In addition, hyperbaric oxygen may improve the healing of radiation-induced injuries by improving oxygen delivery to damaged tissue. (NCI04)
Temperature elevation, sweating, and red flushed face.
Substances that inhibit the biologic effects of the adrenal hormones by interfering with their synthesis, metabolism, or binding to their receptor sites.
A lymphoblastic lymphoma occurring in children.
A primary or metastatic malignant neoplasm affecting the bone or articular cartilage.
Lymphocyte-depleted classical Hodgkin lymphoma occurring in adults.
Nodular sclerosis classical Hodgkin lymphoma occurring in adults.
Mixed cellularity classical Hodgkin lymphoma occurring in adults.
A chronic myelogenous leukemia characterised by the t(9;22)(q34;q11) chromosomal translocation, resulting in the presence of the Philadelphia chromosome and the BCR-ABL1 fusion gene.
An alveolar soft part sarcoma occurring in adults. The most common site of involvement is the extremity, particularly the deep soft tissues of the thigh.
An epithelioid sarcoma occurring in adults.
An undifferentiated pleomorphic sarcoma that occurs during adulthood.
A malignant hemangiopericytoma occurring in the adult population.
A malignant mesenchymoma occurring in adults.
A chronic myelogenous leukemia which does not have the characteristic t(9;22)(q34;q11.2) translocation but it has either a variant translocation or a cryptic translocation that can not be detected by conventional cytogenetic analysis. In such cases the BCR-ABL1 fusion gene is always detected by RT-PCR, FISH, or Southern blot analysis.
An aggressive malignant mesenchymal neoplasm arising from skeletal muscle in adults.
A breast carcinoma characterized by the presence of a predominant ductal carcinoma in situ component and a minor component of invasive carcinoma.
An aggressive carcinoma with a poor prognosis characterized by a presence of both malignant squamous cells and glandular cells.
A non-invasive adenocarcinoma of the breast characterized by a proliferation of monomorphic cells completely filling the lumina. The overall lobular architecture is preserved. It is frequently multifocal (90% in some series) and bilateral. It seldom becomes invasive; however there is an increased risk of infiltrating ductal adenocarcinoma.
A breast carcinoma characterized by the presence of a predominant lobular carcinoma in situ component and a minor component of invasive carcinoma.
An infiltrating lobular adenocarcinoma of the breast. The malignant cells lack cohesion and are arranged individually or in a linear manner (Indian files), or as narrow trabeculae within the stroma. The malignant cells are usually smaller than those of ductal carcinoma, are less pleomorphic, and have fewer mitotic figures.
Paget disease of the breast associated with the presence of a usually high grade ductal carcinoma in situ in the lactiferous glands.
Paget disease involving the skin overlying the mammary gland, accompanied by invasive ductal breast carcinoma.
An adrenal cortex carcinoma characterized by the presence of necrotic changes, hemorrhage, nuclear atypia, and mitotic activity.
L1 acute lymphoblastic leukemia that occurs during childhood.
L2 acute lymphoblastic leukemia that occurs during childhood.
The leukemic counterpart of Burkitt lymphoma occurring in children. The characteristic Burkitt cells are seen in the bone marrow and the peripheral blood. This is an aggressive leukemia.
An acute lymphoblastic leukemia of T-cell origin occurring in children.
An acute B-lymphoblastic leukemia occurring in children.
Non-T non-B acute lymphoblastic leukemia that occurs during childhood.
A non-T, non-B, acute lymphoblastic leukemia in which the lymphoblasts are positive for the common acute lymphoblastic leukemia antigen (CALLA) occurring in children.
Non-T non-B, CALLA negative acute lymphoblastic leukemia that occurs during childhood.
L1 acute lymphoblastic leukemia that occurs during adulthood.
L2 acute lymphoblastic leukemia that occurs during adulthood.
The leukemic counterpart of Burkitt lymphoma occurring in adults. The characteristic Burkitt cells are seen in the bone marrow and the peripheral blood. This is an aggressive leukemia.
An acute T-lymphoblastic leukemia occurring in adults.
An acute B-lymphoblastic leukemia occurring in adults.
Non-T non-B acute lymphoblastic leukemia that occurs during adulthood.
A non-T, non-B, acute lymphoblastic leukemia in which the lymphoblasts are positive for the common acute lymphoblastic leukemia antigen (CALLA) occurring in adults.
Non-T non-B, CALLA negative acute lymphoblastic leukemia that occurs during adulthood.
TdT positive acute lymphoblastic leukemia that occurs during adulthood.
TdT negative acute lymphoblastic leukemia that occurs during adulthood.
TdT negative acute lymphoblastic leukemia that occurs during childhood.
TdT positive acute lymphoblastic leukemia that occurs during childhood.
A conventional osteosarcoma characterized by the presence of spindle shaped cells.
An osteosarcoma characterised by the presence of atypical cartilage of variable cellularity. It may or may not be associated with the presence of myxoid areas or focal bone formation.
A term referring to conventional osteosarcomas which do not have a dominant matrix pattern and contain a mixture of osteoid matrix in combination with chondroid matrix and/or collagen fibers.
A hepatocellular carcinoma occurring in children.
A hepatocellular carcinoma occurring in adults.
Wilms tumor of the kidney characterized by the predominance of the epithelial component. The epithelial cells may form papillary and tubular patterns and pseudorosettes.
Wilms tumor of the kidney characterized by the predominance of the blastema component.
Wilms tumor of the kidney characterized by the predominance of the mesenchymal component.
Wilms tumor of the kidney characterized by the presence of blastema, epithelial, and mesenchymal components (triphasic pattern) or a combination of two of them (biphasic pattern).
A poorly circumscribed morphologic variant of rhabdomyosarcoma occurring in children. The neoplasm is characterized by the presence of primitive skeletal muscle in any stage of myogenesis.
An aggressive malignant mesenchymal neoplasm occurring in children. It is characterized by the presence of round cells with myoblastic differentiation, and a fibrovascular stroma resembling an alveolar growth pattern.
A rare aggressive rhabdomyosarcoma occurring in children. The neoplasm is characterized by the presence of bizarre round, spindle, and polygonal cells.
A mixed rhabdomyosarcoma that occurs in children. The neoplasm is composed of embryonic and alveolar components. It is characterized by the presence of spindle cells with myoblastic differentiation and a myxoid and a fibrous stroma.
An acute erythroid leukemia occurring in adults.
An osteosarcoma usually arising from the metaphysis of long bones. It is characterized by the presence of small cells and osteoid production. The prognosis is usually unfavorable.
An acute myeloid leukemia without maturation occurring in adults.
An acute myeloid leukemia with maturation occurring in adults.
An acute promyelocytic leukemia with PML-RARA fusion occurring in adults.
A carcinoma that originates usually from cells on the surface of the middle and lower third of the ESOPHAGUS. Tumor cells exhibit typical squamous morphology and form large POLYPLOID lesions. Mutations in RNF6, LZTS1, TGFBR2, DEC1, and WWOX1 genes are associated with this cancer.
An acute myelomonocytic leukemia occurring in adults.
A malignant tumor with glandular differentiation arising predominantly from Barrett mucosa in the lower third of the esophagus. Rare examples of esophageal adenocarcinoma deriving from ectopic gastric mucosa in the upper esophagus have also been reported. Grossly, esophageal adenocarcinomas are similar to esophageal squamous cell carcinomas. Microscopically, adenocarcinomas arising in the setting of Barrett esophagus are typically papillary and/or tubular. The prognosis is poor.
An acute monoblastic leukemia occurring in adults.
An acute eosinophilic leukemia occurring in adults.
An acute basophilic leukemia occurring in adults.
An acute megakaryoblastic leukemia occurring in adults.
An adenocarcinoma of the stomach arising on a background of intestinal metaplasia. Microscopically, it is characterized by a glandular pattern and it closely resembles a colonic adenocarcinoma. Grossly, it tends to be nodular, polypoid or ulcerated.
An acute myeloid leukemia without maturation occurring in children.
An adenocarcinoma arising from the stomach. Microscopically, it is characterized by the presence of a diffuse infiltrate, composed of individual adenocarcinoma cells or groups of adenocarcinoma cells in a fibrous or mucoid stroma. Many cells contain mucin droplets, producing a signet-ring configuration.
An acute myeloid leukemia with maturation occurring in children.
A carcinoma that arises from the anus. Anal carcinomas include the anal canal and perianal area (anal margin) carcinomas. Perianal carcinomas are staged separately as skin carcinomas in AJCC v6 and v7 editions. The AJCC v8 edition staging system applies to all carcinomas arising in the anal canal, including carcinomas that arise within anorectal fistulas and those arising in the perianal area (anal margin).
An invasive adenocarcinoma of the colon characterized by the presence of pools of extracellular mucin. Malignant glandular epithelial cells are present in the mucin collections. Mucin constitutes more than 50% of the lesion.
An acute promyelocytic leukemia with PML-RARA fusion occurring in children.
An invasive malignant epithelial tumor that arises from the colon. There is no morphologic, immunophenotypic, or molecular biological evidence of glandular or squamous differentiation.
An acute myelomonocytic leukemia occurring in children.
An acute monoblastic leukemia occurring in children.
An acute monocytic leukemia occurring in children.
An acute eosinophilic leukemia occurring in children.
An acute basophilic leukemia occurring in children.
An acute megakaryoblastic leukemia occurring in children.
An adenocarcinoma arising from the gallbladder. It is the most common malignant tumor of the gallbladder and it is usually well to moderately differentiated. The incidence is higher in patients with gallstones than in patients without gallstones. Signs and symptoms usually present late in the course of the disease and are reminiscent of those of chronic cholecystitis including right upper quadrant pain. Histologic variants include adenocarcinoma of the intestinal type, clear cell adenocarcinoma, mucinous adenocarcinoma, papillary adenocarcinoma, and signet ring adenocarcinoma.
An invasive adenocarcinoma of the rectum characterized by the presence of pools of extracellular mucin. Malignant glandular epithelial cells are present in the mucin collections. Mucin constitutes more than 50% of the lesion.
A carcinoma without evidence of differentiation arising from the gallbladder. The most common variant is the spindle and giant cell type which resembles a sarcoma.
An infiltrating adenocarcinoma arising from the rectum. It is characterized by the presence of malignant glandular cells with prominent intracytoplasmic mucin. These cells constitute more than 50% of the malignant cellular population.
An infiltrating adenocarcinoma of the gallbladder characterized by the presence of metaplastic changes of the malignant glandular cells to squamous cells.
A carcinoma that arises from the gallbladder. It is composed entirely by malignant squamous epithelial cells.
An adenocarcinoma arising from the epithelium of the extrahepatic bile ducts. Signs and symptoms include abdominal pain, anorexia, jaundice, pruritus, nausea and vomiting, and weight loss.
An adenocarcinoma arising from the pancreas. It is characterized by the presence of relatively uniform malignant cells which form acinar patterns. It usually occurs during adulthood. Signs and symptoms include abdominal pain, weight loss, nausea, and diarrhea. It may metastasize to regional lymph nodes and the liver. A minority of patients develop lipase hypersecretion syndrome. This syndrome may be seen in patients with liver metastases and it is characterized by excessive secretion of lipase in the serum, polyarthralgia, and subcutaneous fat necrosis.
A malignant serous cystic epithelial neoplasm arising from the ovary. It is characterized by the presence of glandular, papillary, or solid structures. Psammoma bodies may be present. In well differentiated cases the malignant epithelial cells resemble the cells of fallopian tube epithelium. In poorly differentiated cases the malignant epithelial cells show anaplastic features.
An invasive cystic adenocarcinoma arising from the ovary. It is characterized by the presence of malignant glandular epithelial cells which contain intracytoplasmic mucin. The malignant cells invade the ovarian stroma and the cystic spaces contain mucoid material. In a minority of cases both ovaries are involved by the tumor. The prognosis for stage I tumors is excellent. Patients with metastases usually have a poor prognosis.
A malignant glandular epithelial neoplasm arising from the ovary. It is characterized by the presence of clear and hobnail cells and cystic structures.
An adenocarcinoma arising from the vagina. Morphologic variants include the clear cell, endometrioid, mesonephric, and mucinous adenocarcinoma.
A squamous cell carcinoma arising from the cervical epithelium. It usually evolves from a precancerous cervical lesion. Increased numbers of sexual partners and human papillomavirus (HPV) infection are risk factors for cervical squamous cell carcinoma. The following histologic patterns have been described: conventional squamous cell carcinoma, papillary squamous cell carcinoma, transitional cell carcinoma, lymphoepithelioma-like carcinoma, verrucous carcinoma, condylomatous carcinoma and spindle cell carcinoma. Survival is most closely related to the stage of disease at the time of diagnosis.
An adenocarcinoma arising from the cervical epithelium. It accounts for approximately 15% of invasive cervical carcinomas. Increased numbers of sexual partners and human papillomavirus (HPV) infection are risk factors. Grossly, advanced cervical adenocarcinoma may present as an exophytic mass, an ulcerated lesion, or diffuse cervical enlargement. Microscopically, the majority of cervical adenocarcinomas are of the endocervical (mucinous) type.
A small cell carcinoma arising from the cervix.
The most common morphologic subtype of urinary bladder carcinoma (over 90% of cases). It arises from the transitional epithelium. It most often affects males in their sixth and seventh decades of life. Hematuria is the most common symptom at presentation. Pathologic stage is the strongest predictor of survival.
A squamous cell carcinoma of the bladder arising from metaplastic epithelium. It represents less than 10% of bladder carcinomas. The exception is the Middle East along the Nile Valley, where it represents the most common form of carcinoma because of the endemic nature of schistosomiasis. Bladder squamous cell carcinoma is often associated with long-standing chronic inflammation of the bladder and usually has a poor prognosis. The diagnosis of squamous cell carcinoma of the bladder should be reserved for those tumors that are predominantly keratin forming.
A rare adenocarcinoma arising from metaplastic bladder epithelium. It is frequently associated with long-standing local irritation. The majority of cases originate from the trigone and the posterior wall of the bladder.
A melanoma arising from the choroid, ciliary body, or the iris. It is characterized by the presence of spindle-shaped melanocytes.
Uveal melanoma characterized by the presence of intermediate cells which are similar to but smaller than epithelioid cells.
A squamous cell carcinoma arising from the salivary glands. The majority of patients are in their sixth through eight decades. It usually presents as a rapidly enlarging mass, which may be painful. It usually has an aggressive clinical course.
A parathyroid gland adenoma composed predominantly of neoplastic cells with clear cytoplasm.
A parathyroid gland adenoma that contains a mixture of neoplastic cells (chief cells, oncocytes, and clear cells).
A malignant epithelial neoplasm of the kidney characterized by the presence of lipid-containing clear cells within a vascular network. The tumor may metastasize to unusual sites and late metastasis is common.
A renal cell carcinoma with eosinophilic cytoplasm and high nuclear grade. Granular cells can be seen in any subtype of renal cell carcinoma, including conventional clear cell carcinoma. This term does not represent a specific subtype of renal cell carcinoma and should no longer be used.
A type B1 thymoma which is characterized by an aggressive clinical course (capsular invasion, infiltration of the surrounding tissues) and can metastasize.
Also known as well-differentiated thymic carcinoma, atypical thymoma, or epithelial thymoma, this type of thymoma displays morphologic characteristics of a well-differentiated carcinoma. The majority of cases occur in the anterior mediastinum as Masaoka stage II or stage III tumors. It is almost always invasive, it recurs frequently, and metastasizes in approximately 20% of the cases.
A rare, usually aggressive primary thymic carcinoma, characterized by a syncytial growth of undifferentiated carcinoma cells and the presence of a lymphoplasmacytic infiltrate. More than 40% of cases are associated with Epstein-Barr virus infection.
A type A thymoma which is characterized by an aggressive clinical course (capsular invasion, infiltration of the surrounding tissues) and can metastasize.
A non-seminomatous malignant germ cell tumor arising from the testis. It affects infants, young children, and postpubertal males. It is the most frequently seen testicular neoplasm during childhood. The vast majority of patients present with an asymptomatic scrotal mass. The tumor mimics the yolk sac of the embryo and produces alpha-fetoprotein (AFP). It metastasizes to distant anatomic sites. Prognostic factors relate to the clinical stage and the degree of AFP elevation.
An adenoma arising from the beta cells of the pancreas. It produces insulin.
An endocrine neoplasm arising from the delta cells of the pancreas which produce somatostatin. It does not show evidence of vascular invasion or metastasis to other anatomic sites.
A malignant neuroendocrine tumor arising from the delta cells of the pancreas. It is characterized by inappropriate secretion of somatostatin and associated with diabetes mellitus, hypochlorhydria, gallbladder disease, diarrhea, steatorrhea, anemia, and weight loss. It displays vascular invasion and metastasizes to other anatomic sites.
A benign endocrine neoplasm arising from the alpha cells of the pancreas. It produces glucagon.
A salivary gland carcinoma with low grade histopathologic features. It includes the salivary gland polymorphous low grade adenocarcinoma, salivary gland low grade cribriform cystadenocarcinoma, and low grade salivary gland mucoepidermoid carcinoma. It usually follows a non-aggressive clinical course.
A carcinoma of the salivary gland characterized by serous acinar cell differentiation. The vast majority of cases occur in the parotid gland. It usually presents as a slowly enlarging mass. A minority of patients experience pain. It may recur or metastasize. Multiple recurrences and metastasis to cervical lymph nodes are usually associated with a poor prognosis.
A basal cell carcinoma arising from the lip.
A salivary gland mucoepidermoid carcinoma with low grade histopathologic features. It usually follows a non-aggressive clinical course.
A salivary gland mucoepidermoid carcinoma with intermediate grade histopathologic features.
A usually aggressive salivary gland carcinoma with high grade histopathologic features. It includes the salivary duct carcinoma, salivary gland oncocytic carcinoma, and high grade salivary gland mucoepidermoid carcinoma.
A salivary gland mucoepidermoid carcinoma with high grade histopathologic features. It usually follows an aggressive clinical course.
An adenocarcinoma arising from the salivary gland. It includes the salivary gland polymorphous low grade adenocarcinoma, salivary gland oncocytic carcinoma, salivary gland mucinous adenocarcinoma, salivary gland low grade cribriform cystadenocarcinoma, salivary gland cystadenocarcinoma, salivary gland basal cell adenocarcinoma, salivary gland acinic cell carcinoma, salivary duct carcinoma, and salivary gland adenocarcinoma not otherwise specified.
A nonkeratinizing nasopharyngeal carcinoma characterized by the presence of large cells with vesicular nuclei and prominent nucleoli, a syncytial growth pattern, and a lymphoplasmacytic infiltrate.
A salivary gland carcinoma characterized by the presence of undifferentiated, anaplastic malignant epithelial cells.
An adenoid cystic carcinoma arising from the salivary gland. It is characterized by the presence of epithelial and myoepithelial cells forming tubular, cribriform, and solid patterns. It usually presents as a slow growing mass. Patients may experience pain because of the tumor propensity for perineural invasion. The tumor may follow an aggressive clinical course with recurrences and mestastases to distant sites including lungs, bones, brain, and liver.
Having to do with the time before menopause. Menopause (""change of life"") is the time of life when a woman's menstrual periods stop permanently.
An endometrioid adenocarcinoma of the endometrium showing squamous differentiation.
A high-grade endometrial adenocarcinoma characterized by the presence of large neoplastic cells that display at least focal cytoplasmic clearing. The neoplastic cells form papillary, glandular, or sheet-like structures.
A finding of hairy cell leukemia that has not been treated.
A hairy cell leukemia requiring initial treatment because of the presence of signs of progression. Signs of progression include cytopenia (especially if symptomatic), increasing splenomegaly, and infectious complications. Therapy is not necessary if the patients are asymptomatic and the blood counts are maintained in an acceptable range.
The reemergence of hairy cell leukemia after a period of remission.
A lymph node in the armpit that is free of cancer.
Presence of one or more lymph nodes in the area of the armpit in which cancerous cells have been detected.
The reemergence of lip and/or oral cavity carcinoma after a period of remission.
The reemergence of a hypopharyngeal malignant neoplasm after a period of remission.
The reemergence of laryngeal carcinoma after a period of remission.
The reemergence of nasal cavity or paranasal sinus carcinoma after a period of remission.
Stage I includes: T1, N0, M0. T1: Tumor 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage II includes: T2, N0, M0. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
The reemergence of oropharyngeal carcinoma after a period of remission.
The reemergence of urethral carcinoma after a period of remission
The reemergence of Hodgkin lymphoma after a period of remission during childhood.
Lymphocyte-depleted classical Hodgkin lymphoma occurring in childhood.
Nodular sclerosis classical Hodgkin lymphoma occurring in childhood.
Mixed cellularity classical Hodgkin lymphoma occurring in childhood.
A malignant neoplasm that affects the portion of the urethra that is close to the outside of the body.
You can add as a definition this: A malignant neoplasm that affects the portion of the urethra that is close to the bladder.
A transitional cell carcinoma of the renal pelvis and ureter which has spread from its original site of growth to another anatomic site.
A sarcoma that arises from the soft tissues and occurs during childhood.
A sarcoma that arises from the soft tissues during childhood and has spread from the original site of growth to another anatomic site.
The reemergence of soft tissue sarcoma in childhood after a period of remission.
Ann Arbor Classification: Stage I: Involvement of a single lymph node region (I); or localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE).
Stage I: Involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE). (from PDQ)
Stage I includes: (T1, N0, M0). T1: Tumor limited to ovaries (one or both). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage III includes: T3, N0, M0. T3: Tumor involves one or both both ovaries with microscopically confirmed peritoneal metastasis outside pelvis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
The reemergence of ovarian germ cell tumor after a period of remission.
A rare malignant neoplasm of the soft tissues. It is typically a disease of children and young adults. Most commonly occurs in the paravertebral region, chest wall, pelvis and lower extremities. Treatment includes local excision with consideration for post-operative chemotherapy and/or radiotherapy.
A malignant neoplasm arising from the deep soft tissues in children. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
A synovial sarcoma occurring in childhood.
A malignant hemangiopericytoma occurring in childhood.
A rare malignant neoplasm arising from adipocytes, that occurs in children. The tumor maybe one of several histologic types including well-differentiated, dedifferentiated, myxoid/round cell, and pleomorphic liposarcoma.
An alveolar soft part sarcoma occurring in children. The most common site of involvement is the head and neck, particularly the orbit and tongue.
An aggressive malignant smooth muscle neoplasm, occurring in children. It is characterized by a proliferation of neoplastic spindle cells.
A malignant peripheral nerve sheath tumor occurring in children.
An epithelioid sarcoma occurring in childhood.
A malignant mesenchymoma occurring in children.
The re-emergence of non-Hodgkin lymphoma in adults after a period of remission.
Nonnarcotic agents that relieve pain and reduce fever.
Refractory anemia with excess blasts in transformation (RAEB-T) is characterised by dysplastic features of the myeloid and usually erythroid progenitor cells in the bone marrow and an increased number of myeloblasts in the peripheral blood. The peripheral blood blast count ranges from 20% to 30%. RAEB-T used to be a subcategory of myelodysplastic syndromes in the past. Recently, the term has been eliminated from the WHO based classification of myelodysplastic syndromes. The reason is that the percentage of peripheral blood blasts required for the diagnosis of acute myeloid leukemia has been reduced to 20%. The elimination of the RAEB-T term by the WHO experts has created confusion and ongoing arguments. Currently, according to WHO classification, the vast majority of RAEB-T cases are best classified as acute leukemias (acute leukemias with multilineage dysplasia following myelodysplastic syndrome). A minority of cases are part of RAEB-2.
A radioimmunoconjugate of a rabbit antihuman ferritin IgG labeled with iodine 131 (I-131). Using anti-ferritin IgG as a carrier for I-131 may result in the targeted imaging and/or destruction of cells expressing ferritin. Observed in 35% to 100% of patients with hepatocellular carcinoma, high serum ferritin levels may be due to ferritin production by the tumor cells, or related to the associated iron overload and/or cirrhosis.
A murine monoclonal antibody (MoAb) with application in Immunotherapy and radioimmunodetection in T-cell malignancies. MoAb T101 recognizes a 65kD glycoprotein, CD5 antigen, on the surface of T-cells. When radiolabeled, this MoAb has potential use in the radioimaging or may induce a cytotoxic T-cell response against CD5+ T cells.
A ricin-containing immunotoxin with immunotherapeutic property. Ricin, a plant toxin extracted from castor beans, inhibits protein synthesis via cleaving ribosomal subunit 28S rRNA. Ricin immunoconjugate consists of specific antibody conjugated with the blocked ricin (bR), which has the galactose-binding sites of the B-chain blocked while leaving the ribosome-inactivating ricin A-chain intact, thereby attaining cell-type-specific immunotoxins.
An antimetabolite that affects the metabolism and utilization of purines.
An antimetabolite that affects the metabolism and utilization of pyrimidines.
Class of organic compounds that consist of urea and other compounds including Sulfonyl compounds and have application in pharmaceutical and agricultural preparation. (NCI)
Pharmacological agents which affect the function of the adrenal glands.
A malignant neuroendocrine tumor of the lung. According to histopathologic criteria (WHO 2004), carcinoids are divided into four groups i.e. typical and atypical carcinoids, large cell neuroendocrine carcinoma and small cell lung carcinoma.
An adenocarcinoma which has metastasized from an unknown primary anatomic site.
A squamous cell carcinoma which has metastasized to another anatomic site and the original site of growth has not been identified.
An undifferentiated carcinoma which has metastasized to another anatomic site and the original site of growth has not been identified.
A solid neoplasm (e.g., carcinoma, sarcoma) occurring in adults.
A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors.
Ann Arbor Classification: Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II); or localized involvement of a single extralymphatic organ or site in association with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm (IIE). The number of regions involved may be indicated by a subscript (e.g., II3).
A non-seminomatous germ cell tumor arising from the ovary. It is characterized by the presence of various tissues which correspond to the different germinal layers (endoderm, mesoderm, and ectoderm). According to the level of differentiation of the tissues which comprise the tumor, ovarian teratomas are classified as mature or immature. Mature teratomas are composed of well differentiated, adult-type tissues. Immature teratomas are composed of immature, fetal type-tissues. Mature ovarian teratomas without a fetal-type component have an excellent outcome. The prognosis of immature ovarian teratomas is related to the grade and stage of the tumor.
A teratoma of the ovary composed exclusively or predominantly of a single type of tissue derived from the ectoderm or endoderm. A representative example is struma ovarii which is a teratoma composed exclusively or predominantly of thyroid tissue.
An ovarian malignant germ cell tumor characterized by the presence of at least two different germ cell tumor components. The most common combination of germ cell tumors is dysgerminoma and yolk sac tumor.
A rare acute leukemia of ambiguous lineage in which the blasts do not express markers specific to myeloid or lymphoid lineage.
Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph nodes with or without other lymph node regions on the same side of the diaphragm (IIE). Note: The number of lymph node regions involved may be indicated by a subscript (e.g., II3). (from PDQ)
Stage III: Involvement of lymph node regions on both sides of the diaphragm (III) that may also be accompanied by localized involvement of an extralymphatic organ or site (IIIE), by involvement of the spleen (IIIS), or both (IIIS+E). (from PDQ)
Stage IV: Disseminated (multifocal) involvement of one or more extralymphatic sites with or without associated lymph node involvement or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement. (PDQ)
The reemergence of grade 1 follicular lymphoma after a period of remission.
The reemergence of grade 2 follicular lymphoma after a period of remission.
The reemergence of grade 3 follicular lymphoma after a period of remission.
The reemergence of adult diffuse small cleaved cell lymphoma after a period of remission.
The reemergence of adult diffuse mixed cell lymphoma after a period of remission.
The reemergence of adult diffuse large cell lymphoma after a period of remission.
The reemergence of adult immunoblastic lymphoma after a period of remission.
The reemergence of adult lymphoblastic lymphoma after a period of remission.
The reemergence of adult Burkitt lymphoma after a period of remission.
A transitional cell carcinoma of the renal pelvis and ureter that has not spread to other anatomic sites.
A transitional cell carcinoma of the renal pelvis and ureter that has spread to nearby tissues but has not spread to distant sites.
A squamous cell carcinoma arising from the lip or the oral cavity. The oral cavity squamous cell carcinoma usually arises from the buccal mucosa, tongue, or gums. It occurs predominantly in adults who use tobacco and alcohol and has a tendency to metastasize early to lymph nodes.
A squamous cell carcinoma that arises from the anterior two-thirds of the tongue. It usually presents as a painful ulcerated or nodular lesion.
A squamous cell carcinoma of the oral cavity that arises from the buccal mucosa.
A squamous cell carcinoma of the oral cavity that arises from the floor of the mouth.
A squamous cell carcinoma that arises from the hard palate. It usually presents as a papillary or exophytic mass.
A squamous cell carcinoma that arises from the lip. It affects males more often than females and it usually involves the lower lip. Risk factors include UV exposure, alcohol consumption, smoking, and immunosuppression.
A squamous cell carcinoma of the oral cavity that arises from the lower gingiva.
A squamous cell carcinoma that arises from the retromolar trigone. Pain, often radiating to the ear, is the presenting symptom. The prognosis is poor.
A squamous cell carcinoma of the oral cavity that arises from the upper gingiva.
A well differentiated squamous cell carcinoma arising from the oral cavity. It is an exophytic, warty, slow growing tumor, usually affecting older males. Chronic use of smokeless tobacco is associated with the development of verrucous carcinoma in the oral cavity. Five year disease-free survival rates between 80% and 90% have been reported in patients who underwent extensive surgical removal of the tumor.
A verrucous carcinoma of the oral cavity that arises from the buccal mucosa.
A verrucous carcinoma of the oral cavity that arises from the lower gingiva.
A mucoepidermoid carcinoma arising from the minor salivary glands in the oral cavity. It is often asymptomatic and detected during a routine dental examination.
A mucoepidermoid carcinoma of the oral cavity that arises from the floor of the mouth.
An adenoid cystic carcinoma arising from the minor salivary glands in the oral cavity.
An adenoid cystic carcinoma of the oral cavity that arises from the floor of the mouth.
A squamous cell carcinoma arising from the oropharynx. It predominantly affects adults in their fifth and sixth decades of life and is associated with alcohol and tobacco use. Human papillomavirus is present in approximately half of the cases. It is characterized by a tendency to metastasize early to the lymph nodes. When the tumor is small, patients are often asymptomatic. Physical examination may reveal erythematous or white lesions or plaques. The majority of patients present with locally advanced disease. Signs and symptoms include mucosal ulceration, pain, bleeding, weight loss, neck swelling, and difficulty speaking, chewing, and swallowing. Patients may also present with swollen neck lymph nodes without any symptoms from the oropharyngeal tumor. The most significant prognostic factors are the size of the tumor and the lymph nodes status.
A squamous cell carcinoma that arises from the base of the tongue. It usually presents as a painful ulcerated lesion.
A squamous cell carcinoma that arises from the mucosal lining of the tonsil and tends to metastasize early to the lymph nodes. It predominantly affects middle aged and elderly patients who have a history of alcohol and tobacco use. Patients may present with tonsillar swelling, sore throat, pain radiating to the ipsilateral ear, or a neck mass.
A non-keratinizing carcinoma arising from the oropharynx. It is characterized by the presence of large malignant cells with vesicular nuclei, prominent nucleoli, syncytial growth pattern, and a lymphoplasmacytic infiltrate.
A squamous cell carcinoma arising from the hypopharynx. Signs and symptoms include dysphagia, hemoptysis, and the presence of a neck mass.
A squamous cell carcinoma of the hypopharynx that arises from the postcricoid region.
A squamous cell carcinoma that arises from the larynx. It is the most common histologic type of laryngeal carcinoma. It can arise from the glottis, supraglottic area, or it can be transglottic. Glottic squamous cell carcinoma is the most frequent laryngeal carcinoma in the United States. The symptoms, clinical behavior and the prognosis depend on the site of origin within the larynx.
A squamous cell carcinoma of the larynx that arises from the glottic area. It may remain localized for a long period then in late disease stage, it may spread to the opposite true vocal cord, supraglottic and subglottic areas, and the soft tissues of the neck. Hoarseness is the presenting symptom.
A squamous cell carcinoma of the larynx that arises from the subglottic area. Symptoms include dyspnea and stridor. It spreads to the hypopharynx, trachea, and thyroid gland.
A well differentaited, non-metastasizing squamous cell carcinoma arising from the larynx. It is an exophytic, warty, and slow growing tumor affecting predominantly older men. It is associated with tobacco smoking. Symptoms include hoarseness, airway obstruction, weight loss, dysphagia, and throat pain. If left untreated, it may cause extensive local destruction.
An exophytic, slow growing, well differentiated and non-metastasizing squamous cell carcinoma with pushing margins that arises from the glottic area of the larynx. It usually presents with hoarseness.
An exophytic, slow growing, well differentiated and non-metastasizing squamous cell carcinoma with pushing margins that arises from the subglottic area of the larynx.
An exophytic, slow growing, well differentiated and non-metastasizing squamous cell carcinoma with pushing margins that arises from the supraglottic area of the larynx.
A rare, keratinizing or non-keratinizing squamous cell carcinoma arising from the mucosal epithelium of the nasal cavity or the paranasal sinuses. It affects most often the maxillary sinus. Less frequently, it arises from the nasal cavity, ethmoid sinus, sphenoid sinus, and frontal sinus. Symptoms include nasal fullness, epistaxis, rhinorhea, pain, and paresthesia. Patients with nasal squamous cell carcinoma usually present earlier than patients with maxillary sinus carcinoma and have a better prognosis compared to the latter group.
A squamous cell carcinoma that arises from the nasal cavity mucosa. Signs and symptoms include nasal fullness and obstruction, pain, epistaxis, and the presence of a nasal mass.
A squamous cell carcinoma that arises from the mucosal epithelial surface of the ethmoid, frontal, maxillary, or sphenoid sinus. Patients may present with nasal fullness, obstruction, and/or epistaxis.
A benign neoplasm that arises from the ciliated respiratory mucosa that lines the nasal cavity. It results from the invagination and proliferation of epithelial cells in the underlying stroma. Clinical manifestations include nasal obstruction, epistaxis, and anosmia. It has the tendency to recur and extend to adjacent structures. Inverted papillomas are occasionally associated with the development or presence of carcinomas, usually squamous cell carcinomas.
A benign neoplasm that arises from the ciliated respiratory mucosa that lines the paranasal sinuses. It results from the invagination and proliferation of epithelial cells in the underlying stroma.
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor more than 4 cm in greatest dimension. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0);. IVB (Any T, N3, M0); (T4b, Any N, M0); IVC (Any T, Any N, M1). T4a (lip): Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose. T4a (oral cavity): Tumor invades adjacent structures (e.g., through cortical bone, into deep [extrinsic] muscles of tongue, maxillary sinus, skin of face). T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in dimension. N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M1: Distant metastasis. (AJCC 6th and 7th eds.)
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0);. IVB (Any T, N3, M0); (T4b, Any N, M0); IVC (Any T, Any N, M1). T4a: (oral cavity) Tumor invades adjacent structures (e.g., through cortical bone, into deep [extrinsic] muscles of tongue, maxillary sinus, skin of face). T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in dimension. N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M1: Distant metastasis. (AJCC 6th and 7th eds.)
The reemergence of lip and oral cavity squamous cell carcinoma after a period of remission.
Reemergence of basal cell carcinoma of the lip after a period of remission.
Reemergence of verrucous carcinoma of the oral cavity after a period of remission.
The reemergence of mucoepidermoid carcinoma in the oral cavity after a period of remission.
The reemergence of adenoid cystic carcinoma in the oral cavity after a period of remission.
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension. T3: Tumor measuring more than 4 centimeters in greatest dimension or extension to lingual surface of epiglottis. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB (T4b, Any N, M0); (Any T, N3, M0); IVC (Any T, Any N, M1). T4a: Tumor with moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of larynx. T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension. T3: Tumor measuring more than 4 centimeters in greatest dimension or extension to lingual surface of epiglottis. T4b: Tumor with very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Tumor with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Tumor with metastasis in a lymph node more than 6 cm in greatest dimension. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Reemergence of squamous cell carcinoma of the oropharynx after a period of remission.
Stage I includes: T1, N0, M0. T1: Nasopharyngeal cancer with tumor confined to the nasopharynx, or tumor extending to oropharynx and/or nasal cavity without parapharyngeal extension. Parapharyngeal extension denotes posterolateral infiltration of tumor. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: (T1, N1, M0); (T2, N0, M0); (T2, N1, M0). T1: Nasopharyngeal cancer with tumor confined to the nasopharynx, or tumor extending to oropharynx and/or nasal cavity without parapharyngeal extension. Parapharyngeal extension denotes posterolateral infiltration of tumor. T2: Nasopharyngeal cancer with parapharyngeal extension. Parapharyngeal extension denotes posterolateral infiltration of tumor. N0: No regional lymph node metastasis. N1: Nasopharyngeal cancer with unilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral, retropharyngeal lymph nodes, 6 cm or less in greatest dimension. Midline nodes are considered ipsilateral nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: (T1, N2, M0); (T2, N2, M0); (T3, N0, M0); (T3, N1, M0); (T3, N2, M0). T1: Nasopharyngeal cancer with tumor confined to the nasopharynx, or tumor extending to oropharynx and/or nasal cavity without parapharyngeal extension. Parapharyngeal extension denotes posterolateral infiltration of tumor. T2: Nasopharyngeal cancer with parapharyngeal extension. Parapharyngeal extension denotes posterolateral infiltration of tumor. T3: Nasopharyngeal cancer with tumor involving bony structures of skull base and/or paranasal sinuses. N0: No regional lymph node metastasis. N1: Nasopharyngeal cancer with unilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral, retropharyngeal lymph nodes, 6 cm or less in greatest dimension. Midline nodes are considered ipsilateral nodes. N2: Nasopharyngeal cancer with bilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa. Midline nodes are considered ipsilateral nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: IVA: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0); IVB (Any T, N3, M0); IVC (Any T, Any N, M1). T4: Nasopharyngeal cancer with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit, or with extension to the infratemporal fossa/masticator space. N0: No regional lymph node metastasis. N1: Nasopharyngeal cancer with unilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral, retropharyngeal lymph nodes, 6 cm or less in greatest dimension. Midline nodes are considered ipsilateral nodes. N2: Nasopharyngeal cancer with bilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa. Midline nodes are considered ipsilateral nodes. N3: Nasopharyngeal cancer with metastasis in a lymph node (s) more than 6 cm in greatest dimension and/or to supraclavicular fossa. Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described by Ho. It is defined by three points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, (3) the point where the neck meets the shoulder. This would include caudal portions of levels IV and VB. All cases with lymph nodes (whole or part) in the fossa are considered N3b. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
The reemergence of keratinizing squamous cell carcinoma of the nasopharynx after a period of remission.
The reemergence of undifferentiated carcinoma of the nasopharynx after a period of remission.
Stage I includes: T1, N0, M0. T1: Tumor limited to one subsite of hypopharynx and/or 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor invades more than one subsite of the hypopharynx or an adjacent site, or measures more than 2 cm but not more than 4 cm in greatest diameter without fixation of hemilarynx. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor measuring more than 4 cm in greatest dimension or with fixation of hemilarynx or extension to esophagus. T1: Tumor limited to one subsite of hypopharynx and/or 2 cm or less in greatest dimension. T2: Tumor invades more than one subsite of the hypopharynx or an adjacent site, or measures more than 2 cm but not more than 4 cm in greatest diameter without fixation of hemilarynx. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (T4b, Any N, M0); (Any T, N3, M0); IVC: (Any T, Any N, M1). T4a: Tumor with moderately advanced local disease. Tumor invades the thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue. Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. T1: Tumor limited to one subsite of hypopharynx and/or 2 cm or less in greatest dimension. T2: Tumor invades more than one subsite of the hypopharynx or an adjacent site, or measures more than 2 cm but not more than 4 cm in greatest diameter without fixation of hemilarynx. T3: Tumor measuring more than 4 cm in greatest dimension or tumor with fixation of hemilarynx or extension to esophagus. T4b: Tumor with very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Tumor with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Reemergence of squamous cell carcinoma of the hypopharynx after a period of remission.
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (T4b, Any N, M0); (Any T, N3, M0); IVC: (Any T, Any N, M1). T4a: Supraglottis: Moderately advanced local disease. Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). Glottis: Moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). Subglottis: Moderately advanced local disease. Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). T4b: Supraglottis, Glottis, and Subglottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
The reemergence of squamous cell carcinoma of the larynx after a period of remission.
The reemergence of verrucous carcinoma of the larynx after a period of remission.
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (T4b, Any N, M0); (Any T, N3, M0); IVC: (Any T, Any N, M1). T4a: Maxillary sinus: Moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. Nasal cavity and ethmoid sinus: Moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. T4b: Very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve, nasopharynx, or clivus. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
The reemergence of nasal cavity and paranasal sinus squamous cell carcinoma after a period of remission.
The reemergence of adult T-cell leukemia/lymphoma after a period of remission
A three substituted fluoranthene derivative of the 2-(arylmethylamino)-1,3-propanediol family that intercalates with DNA, causing inhibition of DNA synthesis. (NCI)
An acute myeloid leukemia secondary to a myelodysplastic syndrome or therapy-related. (WHO, 2001)
A primary myelodysplastic syndrome not associated with prior radiation or chemotherapy treatment.
Reemergence of transitional cell carcinoma of the renal pelvis and ureter after a period of remission.
An anal squamous cell carcinoma characterized by the presence of malignant cells with hyperchromatic nuclei and peripheral nuclear palisading.
An oligodendroglioma that arises from the central nervous system and occurs during childhood.
A gestational trophoblastic tumor which has not metastasized to other anatomic sites.
Metastatic gestational trophoblastic tumor in which risk factors are absent.
Metastatic gestational trophoblastic tumor in which risk factors are present.
An antifolate derived from diaminopyrimidine with cytotoxic properties. With a mechanism of action similar to that of methotrexate (MTX), m-azidopyrimethamine blocks tetrahydrofolate synthesis, resulting in depletion of nucleotide precursors and inhibition of DNA, RNA and protein synthesis. This agent is more lipophilic but less potent than MTX. (NCI04)
A synthetic quinolinecarboxylic acid analogue with antineoplastic properties. Brequinar inhibits the enzyme dihydroorotate dehydrogenase, thereby blocking de novo pyrimidine biosynthesis. This agent may also enhance the in vivo antitumor effect of antineoplastic agents such as 5-FU. (NCI04)
A supratentorial embryonal tumor, not otherwise specified that occurs in childhood.
A neoplasm that arises from the choroid plexus in the brain and occurs during childhood.
Stage I includes: T1, N0, M0. T1: Tumor limited to the uterus. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor extends beyond the uterus, within the pelvis. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
Stage III includes: IIIA (T3a, N0, M0); IIIB (T3b, N0, M0); IIIC (T1-T3, N1, M0). T1: Tumor limited to the uterus. T2: Tumor extends beyond the uterus, within the pelvis. T3: Tumor infiltrates abdominal tissues. T3a: Tumor infiltrates abdominal tissues, one side. T3b: Tumor infiltrates abdominal tissues, more than one side. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
Stage IV includes: IVA (T4, Any N, M0); IVB (Any T, Any N, M1). T4: Tumor involves bladder or rectum. M0: No distant metastasis. M1: Distal metastasis (excluding adnexa, pelvic and abdominal tissues). This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
A usually aggressive malignant neoplasm arising from the uterine corpus and less often the cervix. It is characterized by the presence of two components: a malignant epithelial component and a sarcomatous component. In the uterine corpus the epithelial component is usually glandular whereas in the cervix is usually non-glandular. Carcinosarcoma of the cervix, although it is aggressive, it may have a better prognosis compared to the uterine corpus carcinosarcoma.
An aggressive malignant smooth muscle neoplasm, arising from the uterine corpus. It is characterized by a proliferation of neoplastic spindle cells.
An acute monocytic leukemia occurring in adults.
A meningioma that occurs during childhood.
A cholangiocarcinoma occurring in adults.
Malignant neoplasms that develop in HIV infected patients. The most common AIDS-related malignant neoplasms are Kaposi sarcoma, non-Hodgkin lymphoma, anal carcinoma, cervical carcinoma, and Hodgkin lymphoma.
A myelodysplastic syndrome for which a patient has received treatment in the past.
A myelodysplastic syndrome resulting from chemotherapy or radiation therapy treatment for other malignant disorders.
A rare, aggressive malignant mesenchymal neoplasm that arises from the ovary. The prognosis is poor.
A pilocytic astrocytoma that occurs during adolescence.
A low-grade (WHO grade II) astrocytic neoplasm. It is characterized by diffuse infiltration of neighboring central nervous system structures. These lesions typically affect young adults and have a tendency for progression to anaplastic astrocytoma and glioblastoma. Based on the IDH genes mutation status, diffuse astrocytomas are classified as IDH-mutant, IDH-wildtype, and not otherwise specified.
An anaplastic ependymoma occurring in adults.
A WHO grade III malignant glioma of ependymal origin with accelerated growth and an unfavorable clinical outcome, particularly in children. It is characterized by high mitotic activity, often accompanied by microvascular proliferation and pseudo-palisading necrosis. (Adapted from WHO)
A tumor of mixed cell type with astrocytic components as well as ependymoma components.
A mixed glioma characterized by the presence of astrocytic, ependymal, and oligodendroglial neoplastic components.
A WHO grade II tumor composed of a conspicuous mixture of two distinct neoplastic cell types morphologically resembling the tumor cells in oligodendroglioma and diffuse astrocytoma. (WHO)
A pineal parenchymal cell neoplasm (pineocytoma or pineoblastoma) occurring in adults.
A germ cell tumor of the central nervous system occurring in adults.
A malignant meningioma with aggressive clinical course. It recurs in approximately 50-78% of the cases. This category includes the anaplastic (malignant) meningioma, papillary meningioma, and rhabdoid meningioma.
A form of extranodal, high-grade non-Hodgkin B-cell neoplasm, usually large cell or immunoblastic type that originates in the brain, leptomeninges, spinal cord, or eyes and typically remains confined to the CNS.
An synthetic compound containing the organic phosphonate hydroxyethylidene diphosphonate (HEDP) labeled with the radioisotope rhenium Re 186. Re-186 hydroxyethylidene diphosphonate binds to hydroxyapatite in bone, delivering a cytotoxic dose of beta radiation to primary and metastatic bone tumors. Re-186 is a beta emitter with a short half-life, a radioisotope profile that provides localized antitumor radiocytotoxicity while sparing extramedullary bone marrow tissues.
A neuroblastoma which is confined to a specific site and is not amenable to surgical removal.
A murine monoclonal antibody directed against the ganglioside GD2 with potential antineoplastic activity. Monoclonal antibody 14G2A binds to the ganglioside GD2 and induces antibody-dependent cell mediated cytotoxicity and complement-dependent cytotoxicity against GD2-expressing tumor cells. GD2 is overexpressed in malignant melanoma, neuroblastoma, osteosarcoma, and small cell carcinoma of the lung. (NCI04)
A murine monoclonal antibody directed against the cell-surface, tumor-associated antigen ganglioside GD2. Vaccination with monoclonal antibody 3F8 may stimulate a host cytotoxic immune response against tumors that express ganglioside GD2. (NCI04)
A cancer that originates in the sqamous cells that line the surface of the vulva.
The R-enantiomer of the calcium channel blocker verapamil. Dexverapamil competitively inhibits the multidrug resistance efflux pump P-glycoprotein (MDR-1), thereby potentially increasing the effectiveness of a wide range of antineoplastic drugs which are inactivated by MDR-1 mechanisms. This agent exhibits decreased calcium antagonistic activity and toxicity compared to racemic verapamil. (NCI04)
A disorder either associated with an increased risk for malignant transformation (e.g., intraepithelial neoplasia, leukoplakia, dysplastic nevus, myelodysplastic syndrome) or that develops as a result of the presence of an existing malignant neoplasm (e.g., paraneoplastic syndrome).
A situation describing a high degree of difficultly as it relates to intravenous and/or intra-arterial access of an individual's vascular system.
A condition in which the production of red blood cells, white blood cells, and/or platelets by bone marrow stem cells is inhibited, usually as a side effect of treatment with various anti-cancer agents, radiation, or tumor development within the bone marrow.
A substance used to treat tumor cells for synthesis of a tumor-specific immunotherapeutic agent, ethyl chloroformate polymerized tumor protein, for use in Immunotherapy.
A 9-methoxy acridine compound containing a reducible 5-nitro substituent. Pyrazoloacridine appears to intercalate into DNA and inhibit RNA synthesis, DNA synthesis, and the activities of topoisomerases I and II, thereby causing cytotoxicity. (NCI04)
A murine IgG2a monoclonal antibody with potential antineoplastic activity. Monoclonal antibody L6 binds to the L6 antigen, a cell surface glycoprotein overexpressed in many carcinomas, and induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity against L6-expressing tumor cells. This agent may be conjugated with various toxins in order to target their cytotoxic activity to tumor cells expressing the L6 antigen. (NCI04)
A formulation in which liposomes are loaded with the cytokine interleukin-2 (IL-2). By activating cytotoxic T-lymphocytes, such as lymphokine-activated killer cells, and increasing levels of the cytotoxic cytokines interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta), IL-2 may exhibit antitumoral activity. Liposomal formulations of IL-2 may promote entry of the cytokine into target tumor cells and may be used as an immunoadjuvant in cancer vaccine therapy. (NCI04)
Any pulmonary disorder occurring as a consequence of injury to the lungs.
A cancer vaccine consisting of GM2 ganglioside, a melanoma-specific antigen, conjugated with the immunostimulant keyhole limpet hemocyanin. Vaccination with GM2-KLH vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against GM2 ganglioside-expressing melanoma cells, resulting in tumor growth inhibition. (NCI04)
A lymphoma (non-Hodgkin or Hodgkin) arising from the central nervous system and occurring in HIV-positive patients.
A diffuse large cell lymphoma developing in an HIV positive patient.
A 2-amino acid compound with immunomodulatory activity. L-leucyl-L-leucine methyl ester (LLME) is a lysosomotropic agent entering cells via receptor-mediated endocytosis. LLME undergoes a condensation process catalyzed by dipeptidyl peptidase I (DPPI) in lysosomes. Condensation of LLME leads to lysosomal rupture and DNA fragmentation in DPPI-expressing immune cells such as cytotoxic T-cells and natural killer cells. Therefore, this agent may be able to decrease the incidence of graft versus host disease (GVHD) via cytotoxic T-cell depletion. Furthermore, LLME has the potential in augmenting antibody production when used in pretreatment of peripheral blood mononuclear cells (PBMCs), possibly via interfering gene expressions of inflammatory factors.
An indication that an individual has been previously treated with endocrine/hormonal therapy following surgery.
Carcinoma that affects both breasts in a simultaneous or non-simultaneous manner.
Hodgkin lymphoma secondary to AIDS. An increased incidence of Hodgkin lymphomas has been observed in HIV positive patients. Most cases are morphologically classified as lymphocyte depleted or mixed cellularity Hodgkin lymphomas.
An aminophosphonate derivative of a vinca alkaloid with potential antineoplastic activity. Vinfosiltine exerts its antineoplastic action just like its parent compound, vinblastine, by immobilizing tubulin molecules, thereby interrupting microtubule assembly/disassembly dynamics. As a result, vinfosiltine prevents mitotic spindle formation and leads to cell cycle arrest in metaphase.
A subependymoma that occurs during adulthood.
An embryonal tumor with multilayered rosettes, C19MC-altered, occurring in adults.
A papillary meningioma occurring in adults.
A second-generation murine monoclonal antibody based on the antibody B72.3 that is directed against tumor-associated glycoprotein 72 (TAG72). TAG72 is expressed by gastric, breast, pancreatic, colorectal, and ovarian carcinoma cells. (NCI04)
A synthetic uridine pro-drug that is converted to uridine in vivo. Uridine, a pyrimidine nucleotide, has been used in a variety of diseases including depressive disorders and inherited myopathies. (NCI04)
An adenocarcinoma which arises from the exocrine pancreas. Ductal adenocarcinoma and its variants are the most common types of pancreatic adenocarcinoma.
A benign papillary neoplasm that arises endobronchially. It is classified as squamous cell, glandular, or mixed squamous cell and glandular papilloma. Patients usually present with signs and symptoms of bronchial obstruction.
A radioisotope of strontium, a heavy metal found naturally as a non-radioactive element. With a half-life of 50 days, strontium-89 is a beta emitter that is metabolized much like calcium. This agent is preferentially absorbed by osteoblastic bone metastases. (NCI04)
A non-Hodgkin lymphoma occurring in HIV-positive patients. It is composed of a mixture of lymphocytes of various sizes.
A non-Hodgkin lymphoma occurring in HIV-positive patients. It is composed of small cleaved lymphocytes.
An orally active derivative of the short-chain fatty acid butyrate with potential antineoplastic activity. 4-Phenylbutyrate inhibits histone deacetylase, resulting in cell cycle gene expression modulation, reduced cell proliferation, increased cell differentiation, and apoptosis. This agent also initiates fragmentation of genomic DNA, resulting in decreased DNA synthesis and the inhibition of tumor cell migration and invasion. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41827&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41827&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1440"" NCI Thesaurus)
A lymphoblastic lymphoma occurring in HIV-positive patients.
A saturated derivative of sphingosine. As an inhibitor of protein kinase C (PKC), safingol competitively binds to the regulatory phorbol-binding domain of PKC, a kinase involved in tumorigenesis. This agent has been shown to act synergistically with other chemotherapeutic agents and may potentiate chemotherapy drug-induced apoptosis in vitro and in vivo.
A plasma cell neoplasm that secretes an abnormal immunoglobulin, which deposits in various tissues and forms a beta-pleated sheet structure that binds Congo red dye with characteristic birefringence. The sites of involvement include heart, liver, kidney, gut, tongue, nerves, and bone. (WHO, 2001)
A rare, aggressive soft tissue sarcoma that primarily affects adolescents and young adults. It is most commonly found in the abdomen.
A murine anti-idiotypic monoclonal antibody (anti-Id MoAb) that is directed against an idiotype mimicking a disialoganglioside GD3. GD3 represents a major surface marker on most human melanoma cells. Due to poor immunogenicity of GD3, anti-Id MoAb BEC2 (Ab2) was raised against a mouse anti-GD3 MoAb, R24 (Ab1). This anti-Id MoAb was shown to be functionally mimicking GD3 in stimulating an immune response to produce Ab3 that may be used in combination with other adjuvants for treatment of melanomas.
A nutritional supplement gleaned from the exoskeleton of the shark. Shark cartilage inhibits metalloproteinases (MMPs) and possesses antiangiogenic and antimetastatic properties. (NCI04)
A combination of agents containing cyclophosphamide, doxorubicin, etoposide and prednisone.
A recombinant fusion protein composed of the diphtheria toxin with the receptor-binding domain replaced by human epidermal growth factor (EGF). When administered, EGF binds to the endothelial cell growth factor receptor, EGFR, which is upregulated in many solid tumors. After binding to the EGF receptor, the agent is internalized by the cell, where the diphtheria toxin moiety exerts its cytotoxic effect, inhibiting protein synthesis through ADP-ribosylation of elongation factor 2. (NCI04)
A chimeric mouse/human monoclonal antibody with potential antineoplastic activity. Dinutuximab binds to the ganglioside GD2 and induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity against GD2-expressing tumor cells. GD2 is overexpressed in malignant melanoma, neuroblastoma, osteosarcoma, and small cell carcinoma of the lung.
Hodgkin lymphoma that occurs during pregnancy.
The free base form of a synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis. This agent is also a competitive inhibitor of adenosine triphosphate activity.
A vaccine produced from genetically engineered viral vector by introduction of foreign genetic materials to activate immune response in a host.
A peptide vaccine containing a tyrosinase epitope conjugated with keyhole lymphocyte hemocyanin (KLH) with potential antineoplastic activity. Tyrosinase, one of the melanoma differentiation antigens, is the rate-limiting enzyme for melanin synthesis. This tyrosine epitope is conjugated with KLH, which serves as an immunostimulant and a hapten carrier, to enhance immune recognition. Vaccination with tyrosinase-KLH peptide vaccine may produce anti-tyrosinase antibodies as well as elicit a cytotoxic T lymphocyte (CTL) response against cells expressing tyrosinase antigen, resulting in decreased tumor growth.
An acute myeloid leukemia with minimal differentiation occurring in adults.
An acute myeloid leukemia with minimal differentiation occurring in children.
A water-in-oil emulsion that stimulates the T-cell immune response to antigens and may be used in various types of cancer vaccines. (NCI04)
A lymphoma that arises within the eye. Signs and symptoms include decreased vision, uveitis, and vitreous floaters.
A lipophilic disaccharide derivative of muramyl dipeptide (MDP) with strong immunostimulating activity and used as a vaccine adjuvant. MDP, a component of bacterial cell wall, is the minimum chemical structure required for macrophage activation. Due to MDP's toxicity and short duration of action, theramide was developed with improved stability, and can be administered without a liposome carrier. Theramide stimulates macrophage activity, which in turn potentiates other immune responses, including the release of proinflammatory interleukins and tumor necrosis factor alpha (TNF alpha). The release of these cytokines further augments the activation of cellular and humoral immune system.
A retinoid that is used for the treatment of chronic hand ECZEMA unresponsive to topical CORTICOSTEROIDS. It is also used to treat cutaneous lesions associated with AIDS-related KAPOSI SARCOMA.
Stage IV: Disseminated (multifocal) involvement of one or more extralymphatic sites with or without associated lymph node involvement or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement. (from PDQ)
The reemergence of Burkitt lymphoma in childhood after a period of remission.
The reemergence of childhood large cell lymphoma after a period of remission.
A large cell lymphoma occurring in childhood.
A melanoma-associated antigen. When administered in a vaccine formulation, gp100 antigen may stimulate a cytotoxic T cell HLA-A2.1-restricted immune response against tumors that express this antigen, which may result in a reduction in tumor size. (NCI04)
A humanized bivalent antibody directed against both cytotoxic effector cells expressing Fc gamma receptor type I (Fc gammaRI, or CD64) and HER2/neu-overexpressing tumor cells with potential antineoplastic activity. Bispecific antibody MDX-H210 was constructed by chemically linking Fab' fragments of the anti-HER2/neu-specific monoclonal antibody 520C9 and the Fab' fragments of the anti-Fc gammaRI-specific monoclonal antibody H22. This agent selectively binds to both HER2/neu-expressing tumor cells and Fc gammaRI-expressing cytotoxic effector cells, which may trigger antibody-dependent cell-mediated cytotoxicity (ADCC) and cell lysis of HER2/neu-expressing tumor cells. While HER2/neu is overexpressed in a variety of epithelial malignancies, expression of Fc gammaRI is primarily found in cytotoxic immune cells, including monocytes, macrophages, and cytokine-activated polymorphonuclear (PMN) cells.
A murine monoclonal antibody (MoAb) IgG2a, LL2. MoAb LL2 recognizes CD22, a B-lymphocyte-restricted antigen expressed as a cytoplasmic protein in progenitor B cells, and as a cell surface protein in mature B cells. When labeled with radioisotope, MoAb LL2 targets tumor cells that express CD22 antigen and delivers cytotoxic radiation that may be used to treat B-cell lineage cancers.
Daflon 500 is a phlebotonic drug and a vascular protecting agent. It is reported to improve microcirculation in chronic venous insufficiency by improvement of venous tone, inhibition of prostaglandin synthesis, protection against free radicals, activation of the complement system, and increased lymphatic drainage. This results in reduced venous capacitance, distensibility, and emptying time; reduced capillary permeability; and increased capillary resistance. (Angiology 1994 Jun;45(6):419-2)
A human papillomavirus-related neoplasm arising from the anus. Morphologically, it is characterized by an exophytic papillary proliferation of squamous cells and acanthosis.
A grade I, slowly growing meningioma. Only a minority of tumors recur following complete resection.
An electrocardiographic finding suggestive of enlargement or thickening of both ventricles, with a combination of findings which are related to LVH and RVH, such as voltage criteria for LVH in the presence of marked right axis deviation. (CDISC)
Metaplastic changes in the cervical glandular or squamous epithelium.
A benign intraluminal polypoid neoplasm of the esophagus. It includes the squamous papilloma and the giant fibrovascular polyp.
Sensation of unpleasant feeling indicating potential or actual damage to some body structure felt all over, or throughout the body.
A membrane-like structure that extends across the laryngeal lumen close to the level of the vocal cords.
Congenital or acquired deformity of the musculoskeletal system.
The sodium salt form of acyclovir, a synthetic analog of the purine nucleoside, guanosine, with potent antiviral activity against herpes simplex viruses type 1 and 2, varicella-zoster virus and other viruses of the herpesvirus family. After conversion in vivo to the active metabolite acyclovir triphosphate by viral thymidine kinase, acyclovir competitively inhibits viral DNA polymerase by incorporating into the growing viral DNA chain and terminating further polymerization.
The hydrochloride form of eflornithine, a difluoromethylated ornithine compound with antineoplastic activity. Eflornithine irreversibly inhibits ornithine decarboxylase, an enzyme required for polyamine biosynthesis, thereby inhibiting the formation and proliferation of tumor cells. Polyamines are involved in nucleosome oligomerization and DNA conformation, creating a chromatin environment that stimulates neoplastic transformation of cells. (NCI04)
The sodium salt of a pterin derivative with antineoplastic and immunosuppressive properties. As a folate analogue, aminopterin competes for the folate binding site of the enzyme dihydrofolate reductase, thereby blocking tetrahydrofolate synthesis, and resulting in depletion of nucleotide precursors and inhibition of DNA, RNA and protein synthesis. (NCI04)
The sulfate salt form of amphetamine, a synthetic substance related to natural sympathomimetic amines. Amphetamine appears to exert its central nervous system (CNS) and peripheral effects indirectly by inducing the release of biogenic amines from their storage sites in nerve terminals. This agent is a commonly abused psychostimulant drug, which may be snorted, taken orally, smoked, or injected. Amphetamine induces psychologic dependence which is manifested by elevated mood, increased wakefulness, concentration, physical performance and a feeling of well-being. With sustained use, the effects of tachycardia and enhanced alertness diminish while psychotoxic effects such as hallucinations and delusions may occur. (NCI04)
An indazole non-steroidal anti-inflammatory drug (NSAID) with analgesic, antipyretic, and anti-edema properties. Unlike other NSAIDs, benzydamine hydrochloride does not inhibit cyclooxygenases (COX) but stabilizes membranes, resulting in local anesthesia; inhibits the production of pro-inflammatory cytokines; inhibits the generation of reactive oxygen species by neutrophils; inhibits leukocyte aggregation and adhesion; and exhibits antimicrobial properties. (NCI04)
The hydrochloride form of betaine, a crystalline alkaloid occurring in sugar beets and other plants. Betaine, acting as a transmethylating metabolic intermediate, is the oxidation product of choline. Betaine hydrochloride is used as a gastric acidifier supplement.
The hydrochloride salt form of butoxamine, a selective beta-2 adrenergic antagonist. Butoxamine is used primarily in animal and tissue experiments to identify beta-2 receptors and their function.
A synthetic pregnadiene derivative with anti-aldosterone activity.
Agents that produce a soft formed stool, and relax and loosen the bowels, typically used over a protracted period, to relieve CONSTIPATION.
The findings in X-linked chondrodysplasia punctata 2 (CDPX2) range from fetal demise with multiple malformations and severe growth retardation to much milder manifestations, including adults with no recognizable physical abnormalities. At least 95% of liveborn individuals with CDPX2 are female with the following findings: Growth deficiency / short stature. Distinctive craniofacial appearance. Skeletal changes: stippling (chondrodysplasia punctate) on x-rays of the epiphyses of the long bones and vertebrae, the trachea and distal ends of the ribs seen in children prior to completion of normal epiphyseal ossification; rhizomelic (i.e., proximal) shortening of limbs that is often asymmetric; scoliosis. Ectodermal changes: linear or blotchy scaling ichthyosis in the newborn that usually resolves in the first months of life leaving linear or whorled atrophic patches involving hair follicles (follicular atrophoderma); coarse hair with scarring alopecia; occasional flattened or split nails; normal teeth. Ocular changes: cataracts; microphthalmia and/or microcornea. Intellect is usually normal. Rarely affected males have been identified with a phenotype that includes: hypotonia; moderate to profound developmental delay; seizures; cerebellar (primarily vermis) hypoplasia and/or Dandy-Walker variant; and agenesis of the corpus callosum.
The hydrochloride salt form of clomipramine, a tertiary amine salt derivative of dibenzazepine. Clomipramine hydrochloride is a tricyclic antidepressant that acts by reducing the re-uptake of norepinephrine and serotonin in the central nervous system, thereby enhancing the effects of these neurotransmitters. This drug also binds to alpha-adrenergic, histaminergic, and cholinergic receptors which are responsible for the many side effects seen with this agent.
The hydrochloride salt form of the tropane alkaloid cocaine, with central nervous systems (CNS) stimulating and local anesthetic activity. Cocaine binds to the dopamine, serotonin, and norepinephrine transport proteins and inhibits the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. This leads to an accumulation of the respective neurotransmitters in the synaptic cleft and may result in increased postsynaptic receptor activation. Its effect on dopamine levels causes CNS stimulation and euphoria, and ultimately dependence. The mechanism of action through which cocaine exerts its local anesthetic effects is by binding to and blocking the voltage-gated sodium channels in the neuronal cell membrane. By stabilizing neuronal membranes, cocaine inhibits the initiation and conduction of nerve impulses and produces a reversible loss of sensation.
Vaccines or candidate vaccines used to prevent conception.
An aminothiol salt used in the treatment of nephropathic cystinosis. Cysteamine bitartrate enters the cell and reacts with cystine producing cysteine and cysteine-cysteamine mixed disulfide compound, both of which, unlike cystine, can pass through the lysosomal membrane. This prevents the accumulation of cystine crystals in the lysosomes of patients with cystinosis, which can cause considerable damage and eventual destruction of the cells, particularly in the kidneys. (NCI05)
The hydrochloride form of cytarabine, an antimetabolite analogue of cytidine with a modified sugar moiety (arabinose instead of ribose). Cytarabine is converted to the triphosphate form within the cell and then competes with cytidine for incorporation into DNA. Because the arabinose sugar sterically hinders the rotation of the molecule within DNA, DNA replication ceases, specifically during the S phase of the cell cycle. This agent also inhibits DNA polymerase, resulting in a decrease in DNA replication and repair.
A term used for any state of depression that is not psychotic.
The potassium salt form of diclofenac, a benzene acetic acid derivate and nonsteroidal anti-inflammatory drug (NSAID) with analgesic, antipyretic and anti-inflammatory activity. Diclofenac potassium is a non-selective reversible and competitive inhibitor of cyclooxygenase (COX), subsequently blocking the conversion of arachidonic acid into prostaglandin precursors. This leads to an inhibition of the formation of prostaglandins that are involved in pain, inflammation and fever.
A sympathomimetic amine structurally similar to amphetamine with anorexiant activity. Diethylpropion hydrochloride stimulates the central nervous system and increases the release of norepinephrine and dopamine from nerve terminals and inhibits their uptake. This suppresses appetite, increases motor activity, causes euphoria, mental alertness and excitement. This drug may also cause an increase in heart rate and blood pressure. Diethylpropion hydrochloride is used in the treatment of obesity.
A malate salt of diltazem, a benzothiazepine calcium channel blocking agent. Diltiazem inhibits the transmembrane influx of extracellular calcium ions into select myocardial and vascular smooth muscle cells, causing dilatation of coronary and systemic arteries and decreasing myocardial contractility. Because of its vasodilatory activity, this agent has been shown to improve the microcirculation in some tumors, thereby potentially improving the delivery of antineoplastic agents to tumor cells.
The calcium salt of docusate, a dioctyl salt and an emollient laxative with stool-softening activity. Docusate decreases surface tension and emulsification of fecal matter and allows water to penetrate and mix with stool. As a result, it softens the stool.
The hydrochloride salt form of diphenoxylate, a piperidine derivate, chemically related to narcotic meperidine, with antidiarrheal activity and devoid of central nervous system (CNS) activity. Diphenoxylate acts on opioid receptors in the gastrointestinal tract, thereby decreasing gastrointestinal motility and causing constipation or preventing diarrhea.
The hydrochloride salt form of dopamine, a monoamine compound with positive inotropic activity. Dopamine is a naturally occurring catecholamine formed by decarboxylation of dehydroxyphenylalanine and a precursor of norepinephrine and epinephrine. Dopamine binds to alpha-1- and beta-1- adrenergic receptors. Mediated through myocardial beta-1-adrenergic receptors, dopamine increase heart rate and force, thereby increasing cardiac output. Alpha-1-adrenergic receptor stimulation on vascular smooth muscle, leads to vasoconstriction and results in an increase in systemic vascular resistance. Stimulation of dopaminergic receptors in renal vasculature, leads to renal blood vessel dilation, and an increase in glomerular filtration rate, renal blood flow, sodium excretion, and urine output.
A peripheral and central respiratory stimulant with a brief duration of action. Doxapram hydrochloride stimulates respiration by an action on chemoreceptors in the carotid arteries and, at increased dosage, stimulates central respiratory centers in the medulla as well as other parts of the brain and spinal cord. This results in an increased tidal volume and a slightly increased respiratory rate. Doxapram hydrochloride may also improve cardiac output probably due to an increased release of catecholamines. This respiratory stimulant is used in postanesthesia respiratory depression.
Aplasia cutis congenita (ACC) is defined as congenital localized absence of skin. The skin appears as a thin, transparent membrane through which the underlying structures are visible. The location is usually on the scalp (Evers et al., 1995). Approximately 20 to 30% of cases have underlying osseous involvement (Elliott and Teebi, 1997). Autosomal dominant inheritance is most common, but recessive inheritance has also been reported. Cutaneous aplasia of the scalp vertex also occurs in Johanson-Blizzard syndrome (243800) and Adams-Oliver syndrome (AOS; 100300). A defect in the scalp is sometimes found in cases of trisomy 13 and in about 15% of cases of deletion of the short arm of chromosome 4, the Wolf-Hirschhorn syndrome (WHS; 194190) (Hirschhorn et al., 1965; Fryns et al., 1973). Evers et al. (1995) provided a list of disorders associated with aplasia cutis congenita, classified according to etiology. They also tabulated points of particular significance in history taking and examination of patients with ACC.
The chloride salt of a white crystalline bitter alkaloid isolated from the root of the plant Psychotria Ipecacuanha (ipecac root) and other plants with antiemetic and anthelminthic properties. Emetine inhibits protein synthesis in eukaryotic (but not prokaryotic) cells by irreversibly blocking ribosome movement along the mRNA strand and inhibits DNA replication in the early S phase of the cell cycle. (NCI04)
The hydrochloride salt of fenfluramine, an amphetamine derivative and a sympathomimetic stimulant with appetite-suppressant properties. Fenfluramine, which was part of the Fen-Phen anti-obesity medication, stimulates the release of serotonin from vesicular storage, and modulates serotonin transporter function. Since serotonin regulates mood and appetite, among other functions, increased serotonin level results in a feeling of fullness and loss of appetite.
Accumulation of iron in the tissues. It may be a manifestation of an inherited disorder (e.g., hemochromatosis) or acquired (in patients with repeated blood transfusions). Symptoms include hepatomegaly, arthritis, diabetes mellitus, and bronzed skin. If untreated it has a progressive course and may lead to death.
The hydrochloride salt of hydralazine, a phthalazine derivative with antihypertensive and potential antineoplastic activities. Hydralazine alters intracellular calcium release and interferes with smooth muscle cell calcium influx, resulting in arterial vasodilatation. This agent also inhibits the phosphorylation of myosin protein and chelation of trace metals required for smooth muscle contraction, resulting in an increase in heart rate, stroke volume and cardiac output. In addition to its cardiovascular effects, hydralazine inhibits DNA methyltransferase, which may result in inhibition of DNA methylation in tumor cells.
Cronkhite-Canada syndrome is characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, skin hyperpigmentation, and diarrhea. It is associated with high morbidity (summary by Sweetser et al., 2012).
The hydrochloride salt form of isoproterenol, a synthetic catechol compound and potent beta adrenergic agonist with peripheral vasodilator, bronchodilator, and cardiac stimulating properties. Isoproterenol exerts its effect on the beta-1 adrenergic receptors in the myocardium, thereby increasing heart rate and cardiac output. In addition, isoproterenol acts on beta-2 adrenergic receptors in bronchiolar and vascular smooth muscle, thereby causing smooth muscle relaxation.
The sulfate salt form of isoproterenol, a beta-adrenergic receptor agonist with bronchodilator activity. Isoproterenol binds to beta-2 adrenergic receptors in bronchial smooth muscle, thereby activating intracellular adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, relieve bronchospasms, improve mucociliary clearance and inhibit the release of mediators of immediate hypersensitivity from cells, especially from mast cells.
The hydrochloride salt of isoxsuprine, a benzyl alcohol derivative with vasodilator activity. The mechanism of action of isoxsuprine hydrochloride is controversial because this drug has beta-adrenergic agonist activities that are not reversed by beta-adrenergic blockers. Although stimulation of the beta adrenergic receptor increases blood flow to produce vasodilatation, this drug may also have direct effects on the contractility of smooth muscle. Isoxsuprine hydrochloride also causes relaxation of uterine smooth muscle and may also produce positive inotropic and chronotropic effects on the myocardium.
The hydrochloride salt form of loperamide, a synthetic, piperidine derivative and opioid agonist with antidiarrheal activity. Loperamide acts on the mu-receptors in the intestinal mucosa. This leads to a decrease in gastrointestinal motility by decreasing the circular and longitudinal smooth muscle activity of the intestinal wall. This slows intestinal transit and allows for more water and electrolyte absorption from the intestines. Loperamide is not significantly absorbed from the gut and does not cross the blood-brain barrier. Therefore it has no central nervous system effects.
The hydrochloride salt form of meclizine, a synthetic piperazine with anti-emetic, sedative and histamine H1 antagonistic properties. Meclizine hydrochloride blocks the H1 histamine receptor and prevents the symptoms that are caused by histamine activity on capillaries, bronchial and gastrointestinal smooth muscles, including vasodilation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastrointestinal smooth muscles. Meclizine hydrochloride may exert its antiemetic effects by its anticholinergic actions or due to a direct effect on the medullary chemoreceptive trigger zone.
The hydrochloride salt form of levomethadyl acetate, a synthetic mu-receptor agonist with analgesic activity. Levomethadyl acetate hydrochloride mimics the actions of endogenous peptides at CNS opioid receptors, including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia and physical dependence. Levomethadyl acetate hydrochloride has less severe withdrawal symptoms compared to the morphine-like agents. In addition, with chronic use, levomethadyl acetate hydrochloride produces cross-tolerance to the effects of other mu-receptor agonists, thereby decreasing the physical dependence.
The hydrochloride salt of a synthetic nitroimidazole derivative with antiprotozoal and antibacterial activities. Although its mechanism of action is not fully elucidated, un-ionized metronidazole is readily taken up by obligate anaerobic organisms and is subsequently reduced by low-redox potential electron-transport proteins to an active, intermediate product. Reduced metronidazole causes DNA strand breaks, thereby inhibiting DNA synthesis and bacterial cell growth.
The hydrochloride salt form of molindone, a dihydroindolone compound with antipsychotic and anti-schizophrenic properties not structurally related to other major tranquilizers. Molindone hydrochloride exerts its effect by blocking dopamine receptors, probably D2 and D3, in the reticular activating and limbic systems, thereby decreasing dopamine excess in the brain. This leads to a reduction of spontaneous locomotion and aggressiveness, suppression of conditioned response, antagonism of stereotyped behaviour and hyperactivity induced by amphetamines.
The hydrochloride salt form of naphazoline, an imidazole derivative and a direct-acting sympathomimetic amine with vasoconstrictive properties. Upon ocular administration, naphazoline hydrochloride exerts its effect by acting on alpha-adrenergic receptors in the arterioles of the conjunctiva to produce vasoconstriction, resulting in decreased conjunctival congestion and diminished itching, irritation and redness.
The hydrochloride salt of oxycodone, a methylether of oxymorphone and semisynthetic opioid agonist with analgesic and antitussive properties. Oxycodone binds to mu-receptors in the central nervous system (CNS), thereby mimicking the effects of endogenous opiates. In addition to analgesia and a depressive effect on the cough center in the medulla, this agent may cause euphoria, anxiolysis, miosis, sedation, physical dependence, constipation, and respiratory depression, depending on dosage and variations in individual metabolism.
The hydrochloride salt form of oxymorphone, a semisynthetic opioid with a potent analgesic property. Oxymorphone hydrochloride binds to and activates opiate receptors, specifically mu-receptors, in the central nervous system (CNS). This results in sedation, analgesia, decreased gastrointestinal motility, and respiratory depression.
The hydrobromide salt form of hydroxyamphetamine, an indirect-acting sympathomimetic amine with adrenergic properties. Hydroxyamphetamine, when applied topically to the eye, stimulates the release of norepinephrine from postganglionic adrenergic nerves resulting in the stimulation of both alpha and beta adrenergic receptors. Local alpha stimulatory effects include dilation of the pupil, increased flow of aqueous humor, and vasoconstriction; whereas beta stimulatory effects include relaxation of the ciliary muscle and a decreased production in aqueous humor.
The hydrochloride salt form of pargyline, a monoamine oxidase (MAO) inhibitor with antidepressant activity. Pargyline selectively inhibits MAO type B, an enzyme catalyzing the oxidative deamination and inactivation of certain catecholamines, such as norepinephrine and dopamine, within the presynaptic nerve terminals. By inhibiting the metabolism of these biogenic amines in the brain, pargyline increases their concentration and binding to postsynaptic receptors. Increased receptor stimulation may cause downregulation of central receptors which may attribute to pargyline's antidepressant effect.
The sulfate salt form of penbutolol, a lipophilic, nonselective beta-adrenergic receptor antagonist with anti-anginal and antihypertensive activities. Penbutolol competitively binds to and blocks beta-1 adrenergic receptors in the heart, thereby decreasing cardiac contractility and rate. This leads to a reduction in cardiac output and lowers blood pressure. In addition, bisoprolol prevents the release of renin, a hormone secreted by the kidneys that causes constriction of blood vessels.
The hydrochloride salt form of phentermine, a sympathomimetic amine with central nervous system (CNS) stimulant and appetite depressant properties. Phentermine hydrochloride stimulates the release of norepinephrine and dopamine from nerve endings and blocks the reuptake of these monoamines at the neuronal junctions, resulting in CNS stimulation and metabolic effects, including appetite-suppression, decreased gastric acid secretion and increased blood pressure.
cellular state in which there is evidence of intracellular changes which could lead to a neoplastic condition.
The hydrochloride salt form of propoxycaine, a para-aminobenzoic acid ester with local anesthetic activity. Propoxycaine binds to and inhibits voltage-gated sodium channels, thereby inhibiting the ionic flux required for the initiation and conduction of impulses. This results in a loss of sensation.
The hydrochloride form of propranolol, a synthetic beta-adrenergic receptor blocker with antianginal, antiarrhythmic, and antihypertensive properties. Propranolol competitively antagonizes beta-adrenergic receptors, thereby inhibiting beta-adrenergic reactions, such as vasodilation, and negative chronotropic and inotropic effects.
The dihydrochloride salt of the 9-aminoacridine derivative quinacrine with potential antineoplastic and antiparasitic activities. Quinacrine may inhibit the transcription and activity of both basal and inducible nuclear factor-kappaB (NF-kappaB), which may result in the induction of tumor suppressor p53 transcription, the restoration of p53-dependent apoptotic pathways, and tumor cell apoptosis. Continuous NF-kappaB signaling, present in many tumors and in chronic inflammatory processes, promotes the expression of antiapoptotic proteins and cytokines while downregulating the expression of proapoptotic proteins, such as p53.
The hydrochloride salt form of rimantadine, a cyclic amine and alpha-methyl derivative of amantadine with antiviral activity. Although the exact mechanism of action of rimantadine is not understood, this agent appears to exert its antiviral effect against influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the uncoating of the virus and subsequent release of infectious viral nucleic acids into the cytoplasm of infected cells.
The sodium salt form of sulfacetamide, a synthetic sulfanylacetamide derivative with bacteriostatic activity. Sulfacetamide inhibits bacterial folic acid synthesis by competing with para amino benzoic acid. With a broad spectrum of action, it is used as an anti-infective topical agent to treat skin infections and as an oral agent for urinary tract infections. (NCI04)
The hydrochloride salt form of trazodone, a synthetic triazolopyridine derivative with antidepressant and sedative properties. Based on studies from animal models, trazodone selectively inhibits the re-uptake of serotonin by synaptosomes in the brain, thereby increasing serotonin levels in the synaptic cleft and potentiating serotonin activity. Trazodone is not a monoamine oxidase inhibitor and, unlike amphetamine-type drugs, does not stimulate the central nervous system. The sedative effect of trazodone is likely via alpha-adrenergic and mild histamine H1 blocking actions.
The chloride salt form of tubocurarine, a naturally occurring curare alkaloid isolated from the bark and stem of Chondodendron tomentosum with a muscle relaxant property. Tubocurarine chloride competes with acetylcholine for the nicotinic receptors at the neuromuscular junction of skeletal muscles, thereby inhibiting the action of acetylcholine and blocking the neural transmission without depolarizing the postsynaptic membrane. This may lead to skeletal muscle relaxation and paralysis.
The hydrochloride salt of the anthracycline antineoplastic antibiotic idarubicin. Idarubicin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis. Due to its high lipophilicity, idarubicin penetrates cell membranes more efficiently than other anthracycline antibiotic compounds
The hydrochloride salt form of mefloquine, a piperidinyl quinidine with antimalarial activity. Although the exact mechanism of mefloquine hydrochloride is largely unknown, this agent acts as a blood schizonticide and probably exert its actions by interacting with the phospholipid bilayer, thereby interfering with the stability of the cell membrane and causing cell lysis. Mefloquine hydrochloride is active against Plasmodium falciparum and Plasmodium vivax.
The sodium salt form of ganciclovir, a synthetic, antiviral, purine nucleoside analog with antiviral activity, especially against cytomegalovirus (CMV). Ganciclovir sodium is a prodrug that is phosphorylated and subsequently converted into its triphosphate form, the active metabolite ganciclovir-5-triphosphate (ganciclovir-TP), in the infected cells by cellular kinases. Ganciclovir-TP competes as a substrate with nucleotide triphosphates for viral DNA polymerase. Once it gets incorporated into DNA strand, it prevents further polymerization of DNA, thereby interfering with viral DNA replication.
The calcium salt form of nedocromil, a pyranoquinolone derivative with anti-inflammatory properties. Nedocromil inhibits the activation and release of inflammatory mediators (leukotrienes, histamine and prostaglandins) from a variety of cells involved in hypersensitivity reactions, including mast cells, eosinophils, neutrophils, macrophages, monocytes and platelets. As a result, nedocromil sodium inhibits both immediate and late bronchoconstriction, decreases bronchial hyperresponsiveness and inhibits recruitment of other inflammatory cells into the airway epithelium.
A drug used to prevent blood clots from forming or to treat blood clots that have formed in patients with cancer or other conditions. Dalteparin sodium is a type of anticoagulant.
A condition with recurring discomfort or pain in the URINARY BLADDER and the surrounding pelvic region without an identifiable disease. Severity of pain in interstitial cystitis varies greatly and often is accompanied by increased urination frequency and urgency.
Sneddon syndrome is a noninflammatory arteriopathy characterized by onset of livedo reticularis in the second decade and onset of cerebrovascular disease in early adulthood (summary by Bras et al., 2014). Livedo reticularis occurs also with polyarteritis nodosa, systemic lupus erythematosus, and central thrombocythemia, any one of which may be accompanied by cerebrovascular accidents (Bruyn et al., 1987).
A polysymptomatic condition believed by clinical ecologists to result from immune dysregulation induced by common foods, allergens, and chemicals, resulting in various physical and mental disorders. The medical community has remained largely skeptical of the existence of this ""disease"", given the plethora of symptoms attributed to environmental illness, the lack of reproducible laboratory abnormalities, and the use of unproven therapies to treat the condition. (From Segen, Dictionary of Modern Medicine, 1992)
A rare childhood syndrome characterized by the progressive or sudden inability to understand and use spoken language (aphasia) and paroxysmal electrical brain waves. Patients develop epileptic seizures and behavioral changes.
A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)
Energy that is generated by the transfer of protons or electrons across an energy-transducing membrane and that can be used for chemical, osmotic, or mechanical work. Proton-motive force can be generated by a variety of phenomena including the operation of an electron transport chain, illumination of a PURPLE MEMBRANE, and the hydrolysis of ATP by a proton ATPase. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p171)
Any substance that inhibits the activity of viral reverse transcriptase, an RNA-dependent DNA polymerase that transcribes viral RNA into DNA during virus replication.
A rare metabolic disorder that affects neonates. It is characterized by damage of the white matter in the brain and degeneration of the adrenal glands. It manifests with hyperactivity, paralysis, muscular weakness, crossed eyes, hearing loss, seizures, and coma.
A rare, autosomal recessive inherited metabolic disorder characterized by high levels of pipecolic acid in the blood, leading to neuropathy and hepatomegaly.
A group of congenital disorders of lipid metabolism, caused by loss of the normal peroxisomes. Signs and symptoms include developmental delays, mental retardation, facial abnormalities, hepatomegaly, and hypotonia.
An autosomal recessive form of CHONDRODYSPLASIA PUNCTATA characterized by defective plasmalogen biosynthesis and impaired peroxisomes. Patients have shortened proximal limbs and severely disturbed endochondral bone formation. The metabolic defects associated with the impaired peroxisomes are present only in the rhizomelic form of chondrodysplasia punctata. (From Scriver et al, Metabolic Basis of Inherited Disease, 6th ed, p1497)
An antineoplastic agent that replaces hydrogen atom(s) in nucleophilic moieties with alky radical(s), hindering proper function. Alkylating agents exhibit cytotoxic effects through the alkylation of DNA, resulting in strand cross-linking, ultimately inhibiting DNA replication and cancer cell growth.
A disorder involving the aberrant infiltration and aggregation of leukocytes into the vasculature of the body. Leukostasis is typically detected in the brain and lungs of persons with leukemia. It requires substantial ablative modalities to both reduce the number of cells present and to ensure dispersion of the aggregates.
Unexplained symptoms reported by veterans of the Persian Gulf War with Iraq in 1991. The symptoms reported include fatigue, skin rash, muscle and joint pain, headaches, loss of memory, shortness of breath, gastrointestinal and respiratory symptoms, and extreme sensitivity to commonly occurring chemicals. (Nature 1994 May 5;369(6475):8)
The measure of a BLOOD VESSEL's ability to increase the volume of BLOOD it holds without a large increase in BLOOD PRESSURE. The vascular capacitance is equal to the change in volume divided by the change in pressure.
Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475)
Classified as bronchodilators (beta-adrenoreceptor agonists, xanthines, muscarinic-receptor antagonists) and anti-inflammatory agents (glucocorticoids, cromolyn), natural or synthetic Anti-asthmatic Agents relieve asthma (a recurrent airway obstruction) in multiple ways and at various sites, by reducing bronchial spasm, dyspnea, allergic reaction, local inflammation, and pain. Other agents, such as anti-histamine and antibiotics, may also be used in asthma. (NCI04)
Any agent that affects hormone levels and exerts antineoplastic effects. Antineoplastic hormonal/endocrine agents treat either hormone-dependent or hormone-sensitive cancers by modulating hormone levels and manipulating the endocrine system.
A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.
Drugs considered essential to meet the health needs of a population as well as to control drug costs.
A genetically heterogeneous group of heritable disorders resulting from defects in protein N-glycosylation.
A benign or malignant mesenchymal neoplasm arising from smooth, skeletal, or cardiac muscle.
A benign or malignant neoplasm (tumour) originating in the vascular system. [HPO:probinson]
Neoplasms that affect the bone marrow. Such neoplasms may arise in the bone marrow (e.g. myeloid leukemias) or may involve the bone marrow as secondary, metastatic tumors (e.g. metastatic carcinomas to the bone marrow).
A neoplastic proliferation of the epithelial cells that line the acini and the ducts of the prostate gland. The neoplastic epithelial cells are confined within the acini and the ducts and they do not invade the surrounding prostatic stroma. Morphologically, it is classified as low or high grade.
A syndrome characterized by chronic, well-established DIARRHEA (greater than one month in duration) without an identified infectious cause after thorough evaluation, in an HIV-positive individual. It is thought to be due to direct or indirect effects of HIV on the enteric mucosa. HIV enteropathy is a diagnosis of exclusion and can be made only after other forms of diarrheal illness have been ruled out. (Harrison's Principles of Internal Medicine, 13th ed, pp1607-8; Haubrich et al., Bockus Gastroenterology, 5th ed, p1155)
Enhancement of viral infectivity caused by non-neutralizing antibodies. There are at least two mechanisms known to account for this: mediation by Fc receptors (RECEPTORS, FC) or by complement receptors (RECEPTORS, COMPLEMENT). Either the virus is complexed with antiviral IMMUNOGLOBULIN G and binds to Fc receptors, or virus is coated with antiviral IMMUNOGLOBULIN M and binds to complement receptors.
An infant whose weight at birth is less than 1500 grams (3.3 lbs), regardless of gestational age.
Infections with bacteria of the genus BURKHOLDERIA.
The ability of tumors to evade destruction by the IMMUNE SYSTEM. Theories concerning possible mechanisms by which this takes place involve both cellular immunity (IMMUNITY, CELLULAR) and humoral immunity (ANTIBODY FORMATION), and also costimulatory pathways related to CD28 antigens (CD28 ANTIGENS) and CD80 antigens (B7-1 ANTIGEN).
Drugs used for their effects on the respiratory system.
A highly fatal, acute hemorrhagic fever, clinically very similar to MARBURG VIRUS DISEASE, caused by EBOLAVIRUS, first occurring in the Sudan and adjacent northwestern (what was then) Zaire.
diamine oxidase and nitric oxide synthase inhibitor; an advanced glycosylation end product inhibitor; used in the treatment of diabetic complications.
A synthetic derivative of dimethylphenyl-triazene related to dacarbazine, with antineoplastic properties. Related to the agent dacarbazine, CB10-277 is converted in vivo to a monomethyl triazene form that alkylates DNA, resulting in inhibition of DNA replication and repair; in addition, this agent may act as a purine analogue, resulting in inhibition of DNA synthesis, and may interact with protein sulfhydryl groups. (NCI04)
A derivative of the antitumor antibiotic spergualin with immunosuppressant activity. Gusperimus inhibits the interleukin-2-stimulated maturation of T cells to the S and G2/M phases and the polarization of the T cells into IFN-gamma-secreting Th1 effector T cells, resulting in the inhibition of growth of activated naive CD4 T cells; this agent may suppress growth of certain T-cell leukemia cell lines. (NCI04)
A derivative of the antitumor antibiotic spergualin with immunosuppressant activity. Gusperimus inhibits the interleukin-2-stimulated maturation of T cells to the S and G2/M phases and the polarization of the T cells into IFN-gamma-secreting Th1 effector T cells, resulting in the inhibition of growth of activated naive CD4 T cells; this agent may suppress growth of certain T-cell leukemia cell lines. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40369&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=40369&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1598"" NCI Thesaurus)
The sodium salt form of fosphenytoin, a prodrug that is hydrolyzed to the anticonvulsant phenytoin upon parental administration. Phenytoin exerts its effect most likely through an enhancement of sodium efflux from neurons in the motor cortex. This leads to a suppression of excessive neuronal firing and spread of seizure activity. Other physiologic effects from actions of phenytoin include modulation of the voltage-dependent calcium channels of neurons, inhibition of calcium flux across neuronal membranes and enhancement of sodium-potassium ATPase activity of neurons and glial cells. (NCI05)
Structural analog of taurine that is used for the prevention of relapse in individuals with ALCOHOLISM.
An immunomodulator, 3,6-bis(2-piperidinoethoxy) acridine trihydrochloride, used in a phase I study for possible immunostimulatory effects in colorectal cancer. (NCI)
A synthetic, nonsteroidal antiandrogen. Bicalutamide competitively binds to cytosolic androgen receptors in target tissues, thereby inhibiting the receptor binding of androgens. This agent does not bind to most mutated forms of androgen receptors. (NCI04)
The disodium salt form of tiludronate, a first-generation, non-nitrogenous bisphosphonate analogue of endogenous pyrophosphate. Tiludronate adsorbs to hydroxyapatite cells, and although the exact mechanism through which this bisphosphonate exerts its effect has yet to be fully elucidated, tiludronate appears to inhibit protein-tyrosine-phosphatase (PTP) in osteoclasts, thereby disrupting the cytoskeletal ring structure and suppressing the bone resorbing activity of osteoclasts. In addition, tiludronate appears to inhibit the vacuolar-type proton ATPase (V-ATPase) in osteoclasts. Altogether, this may reduce the number of osteoclasts, inhibit abnormal bone resorption and reduce bone turnover.
brand name of lansoprazole a drug used to treat heartburn
A synthetic, acyclic, monophosphate nucleotide analog of deoxycytidine with antiviral activity, and mostly used against cytomegalovirus (CMV). After incorporation into the host cell, cidofovir is phosphorylated by pyruvate kinases to its active metabolite cidofovir diphosphate. Cidofovir diphosphate, bearing structural similarity to nucleotides, competes with deoxycytosine-5-triphosphate (dCTP) for viral DNA polymerase and gets incorporated into the growing viral DNA strands. As a result, it prevents further DNA polymerization and disrupts DNA replication of viruses.
A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.
A hormone therapy drug used to decrease the production of estrogen.
An orally bioavailable chelate composed of zinc and L-carnosine, with potential gastroprotective, anti-oxidant, anti-ulcer and anti-inflammatory activities. Upon administration, polaprezinc increases the expression of various anti-oxidant enzymes, such as superoxide dismutase 1 (SOD-1), SOD-2, heme oxygenase-1 (HO-1), glutathione S-transferase (GST), glutathione peroxidase (GSH-px), peroxidredoxin-1 (PRDX1; PRXI) and PRXD5 (PRXV) in the gastric mucosa, which protect cells against reactive oxygen species (ROS). In addition, this agent inhibits the activity of the transcription factor nuclear factor-kappaB (NF-kappaB) and reduces the expression of several pro-inflammatory cytokines, such as interleukin (IL) 1beta, IL-6, IL-8, and tumor necrosis factor alpha (TNF-a). Polaprezinc also increases the expression of various growth factors, such as platelet-derived growth factor-B (PDGF-B), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), and various heat shock proteins (HSPs), including HSP90, HSP70, HSP60, HSP47, HSP27, and HSP10. This protects against damages to, and accelerates healing of the gastric mucosa.
A nucleoside analog of deoxyguanine with broad-spectrum antiviral activity. Lobucavir is phosphorylated in vivo to its triphosphate form and inhibits viral DNA polymerase and viral DNA replication.
The calcium salt of atorvastatin, a synthetic lipid-lowering agent. Atorvastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent increases the number of LDL receptors on hepatic cell surfaces, enhancing the uptake and catabolism of LDL and reducing LDL production and the number of LDL particles, and lowers plasma cholesterol and lipoprotein levels. Like other statins, atorvastatin may also display direct antineoplastic activity, possibly by inhibiting farnesylation and geranylgeranylation of proteins such as small GTP-binding proteins, which may result in the arrest of cells in the G1 phase of the cell cycle. This agent may also sensitize tumor cells to cyctostatic drugs, possibly through the mTOR-dependent inhibition of Akt phosphorylation.
A pyrrole and heptanoic acid derivative, HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITOR (statin), and ANTICHOLESTEREMIC AGENT that is used to reduce serum levels of LDL-CHOLESTEROL; APOLIPOPROTEIN B; and TRIGLYCERIDES. It is used to increase serum levels of HDL-CHOLESTEROL in the treatment of HYPERLIPIDEMIAS, and for the prevention of CARDIOVASCULAR DISEASES in patients with multiple risk factors.
The mesylate salt form of saquinavir, a peptidomimetic inhibitor of human immunodeficiency virus (HIV) protease.
A peptidomimetic inhibitor of human immunodeficiency virus (HIV) protease.
A benzoyl mustard derivative of the antiviral agent distamycin A with potential antineoplastic activity. Tallimustine selectively binds to A-T rich regions in the minor groove of DNA and alkylates at the N3 position of adenine in a highly sequence-specific manner. This prevents DNA replication, inhibits cellular proliferation and triggers apoptosis. Moreover, unlike other clinical nitrogen mustards, tallimustine does not carry out guanine-N7 alkylation in the major groove of DNA, which may lead to a high selectivity of action.
An immunotoxin consisting of a murine anti-CD5 monoclonal antibody conjugated to the ricin A chain. The anti-CD5 monoclonal antibody component binds to CD5, a T-cell associated antigen, thereby targeting the delivery of the cytotoxic ricin A chain to T-cells. The ricin A chain component binds to T-cells and disrupts ribosomal activity and protein synthesis and induces cell cycle arrest. (NCI04)
A competitive and reversible angiotensin II receptor antagonist with anti-hypertensive property. Eprosartan blocks the binding of angiotensin II to the angiotensin (AT)1 receptor in vascular smooth muscle, thereby blocking the principal pressor action of angiotensin II on the renin-angiotensin system resulting in vascular dilatation. In addition, this agent blocks angiotensin II -induced stimulation of aldosterone synthesis and secretion by the adrenal cortex, cardiac contraction, renal resorption of sodium, activity of the sympathetic nervous system, and smooth muscle cell growth. Furthermore, eprosartan inhibits sympathetic norepinephrine production, thereby further reducing blood pressure.
brand name of quetiapine, a drug used to treat schizophrenia and bipolar disorder
A 6-0-butanoyl ester derivative of castanospermine, a compound derived from the Australian chestnut with activity against hepatitis C virus. Celgosivir rapidly converts to castanospermine in the body, where it is a potent inhibitor of alpha-glucosidase I, a host enzyme required for viral assembly, release, and infectivity.
A semisynthetic, broad-spectrum, beta-lactamase-resistant, third-generation cephalosporin with antibacterial activity. Cefditoren binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
A hydrazone and pyridazine derivative; the levo-form is a phosphodiesterase III inhibitor, calcium-sensitizing agent, and inotropic agent that is used in the treatment of HEART FAILURE.
A sulfated polysaccharide isolated from various Arthrobacter bacterial species. Possessing potential antiangiogenic and antineoplastic properties, tecogalan binds to basic fibroblast growth factor (bFGF), thereby preventing bFGF from binding to its receptors. Disruption of this receptor binding results in the inhibition of bFGF-stimulated endothelial cell growth, proliferation, and migration. (NCI04)
A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1.
A nonpeptide angiotensin II antagonist with antihypertensive activity. Irbesartan selectively and competitively blocks the binding of angiotensin II to the angiotensin I receptor. Angiotensin II stimulates aldosterone synthesis and secretion by adrenal cortex, which decreases the excretion of sodium and increases the excretion of potassium. Angiotensin II also acts as a vasoconstrictor in vascular smooth muscle. (NCI05)
A trimethoprim analogue and selective inhibitor of microbial dihydrofolate reductase, with antibacterial activity. Epiroprim inhibits the bacterial enzyme dihydrofolate reductase, selectively blocking the conversion of dihydrofolic acid to tetrahydrofolic acid. By depleting folate molecules, epiroprim inhibits bacterial nucleic acid synthesis.
A Fab fragment of the chimeric monoclonal antibody 7E3 and inhibitor of the glycoprotein (GP) IIb/IIIa receptor, that blocks platelet aggregation. Abciximab binds to the GP IIb/IIIa receptor on the platelet membrane, which inhibits the binding of fibrinogen to the GP IIb/IIIa receptor. This prevents both platelet aggregation and thrombus formation.
A synthetic, topical retinoid. Tazarotene induces the expression of tazarotene-induced gene 3 (TIG3), a tumor suppressor gene. In psoriasis, tazarotene normalizes abnormal keratinocyte differentiation and reduces their hyperproliferation. (NCI04)
A thiazolidinedione that functions as a selective agonist for PPAR GAMMA. It improves INSULIN SENSITIVITY in adipose tissue, skeletal muscle, and the liver of patients with TYPE 2 DIABETES MELLITUS.
A boronated phenylalanine complexed with fructose to increase its solubility. When exposed to neutron irradiation, boronophenylalanine absorbs neutrons and self-destructs releasing short-range alpha radiation and 'recoil' lithium in tumor cells, resulting in alpha radiation-induced tumor cell death. This highly selective, localized radiotargeting of tumor cells, known as boron neutron capture therapy (BNCT), spares adjacent normal tissues.
The maleate salt of methylergonovine, a semi-synthetic ergot alkaloid with vasoconstrictive and uterotonic effects. Methylergonovine stimulates serotoninergic and dopaminergic receptors as well as inhibits the release of endothelial-derived relaxation factor. This results in arterial vasoconstriction and increased uterine smooth muscle contractions.
A rat IgG2b monoclonal antibody directed against the cell surface glycoprotein CD52. It is used in hematopoietic stem cell transplantation to prevent graft vs host disease by eliminating T cells via antibody dependent cell cytotoxicity in vivo.
A random polymer of L-ALANINE, L-GLUTAMIC ACID, L-LYSINE, and L-TYROSINE that structurally resembles MYELIN BASIC PROTEIN. It is used in the treatment of RELAPSING-REMITTING MULTIPLE SCLEROSIS.
An orally bioavailable, synthetic, highly selective adenosine A3 receptor (A3AR) agonist with potential antineoplastic activity. Namodenoson selectively binds to and activates the cell surface-expressed A3AR, deregulating Wnt and NF-kB signal transduction pathways downstream, which may result in apoptosis of A3AR-expressing tumor cells. A3AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of various solid tumor cell types, including hepatocellular carcinoma (HCC) cells, and plays an important role in cellular proliferation.
A disulfide agent that stimulates T and B-cell functions and exhibits anti-tumor and immunostimulant activity. (NCI)
Circulating 38-kDa proteins that are internal peptide fragments of PLASMINOGEN. The name derives from the fact that they are potent ANGIOGENESIS INHIBITORS. Angiostatins contain four KRINGLE DOMAINS which are associated with their potent angiostatic activity.
a drug used to treat attention deficit hyperactivity disorder
A nitrile and triazole derivative that acts as a selective nonsteroidal aromatase inhibitor. It is used in the treatment of ESTROGEN NUCLEAR RECEPTOR-positive breast cancer in postmenopausal women.
A small molecule iodobenzamide with potential cytotoxic and antineoplastic activities. Although the mechanism of action is unknown, iniparib appears to be cytotoxic in cells with DNA alterations or DNA damage, like that found in tumor cells with mutations in the ataxia telangiectasia mutated (ATM) gene. ATM encodes a serine/threonine protein kinase and mutations of the gene are associated with ataxia telangiectasia and contribute to certain cancers such as T-cell acute lymphoblastic leukemia, B-cell chronic lymphocytic leukemia and B-cell non-Hodgkin lymphomas.
The hydrochloride salt form of alosetron, a potent and selective 5-HT3 receptor antagonist. Alosetron blocks the actions of serotonin at 5-HT3 sites in the peripheral nervous system, particularly on enteric and nociceptive sensory neurons, thereby affecting the regulation of visceral pain, decreasing gastrointestinal contraction and motility, and decreasing gastrointestinal secretions. This agent is used to treat diarrhea-predominant irritable bowel syndrome in women.
A potent and selective 5-HT3 receptor antagonist. Alosetron blocks the actions of serotonin at 5-HT3 sites in the peripheral nervous system, particularly on enteric and nociceptive sensory neurons, thereby affecting the regulation of visceral pain, decreasing gastrointestinal contraction and motility, and decreasing gastrointestinal secretions. This agent is used to treat diarrhea-predominant irritable bowel syndrome in women.
A peptidomimetic agent that inhibits both HIV-1 and HIV-2 proteases. Ritonavir is highly inhibited by serum proteins but boosts the effect of other HIV proteases by blocking their degradation by cytochrome P450.
A neurotoxin with potential anticancer property. Chlorotoxin (CTX) is a 36-amino acid peptide found in the venom of the deathstalker scorpion, and a chloride channel blocker. This toxin binds preferentially to glioma cells via the transmembrane endopeptidase matrix metalloproteinase-2 (MMP-2), and thereby prevents the spread of tumor cells. MMP-2 is specifically up-regulated in gliomas and related cancers, but is not normally expressed in brain.
A recombinant therapeutic agent which is chemically identical to or similar to endogenous human insulin. In lispro insulin, the amino acid proline at B-28 and the amino acid lysine at B-29 are reversed, resulting in the rapid dissolution of this insulin to a monomer that is absorbed rapidly after subcutaneous administration. Lispro insulin is equipotent to human insulin on a molar basis but its effects are faster and of shorter duration. Endogenous insulin, a pancreatic hormone composed of two polypeptide chains, is important in the normal metabolism of carbohydrates, proteins and fats, promoting glucose utilization and protein synthesis; it has anabolic effects on many types of tissues. (NCI04)
A semisynthetic analogue of camptothecin with antineoplastic activity. Lurtotecan selectively stabilizes the topoisomerase I-DNA covalent complex and forms an enzyme-drug-DNA ternary complex. As a consequence of the formation of this complex, both the initial cleavage reaction and religation steps are inhibited and subsequent collision of the replication fork with the cleaved strand of DNA results in inhibition of DNA replication, double strand DNA breakage and triggering of apoptosis. Independent from DNA replication inhibition, lurtotecan also inhibits RNA synthesis, multi-ubiquitination and degradation of topoisomerase I and chromatin reorganization.
A 4:1 mixture of phenylacetate and phenylacetylgluatmine, degradation products of the antineoplaston agent A10. Antineoplaston AS2-1 inhibits the incorporation of L-glutamine into tumor-cell proteins, leading to cell cycle arrest in the G1 phase and inhibition of mitosis. This agent may also inhibit RAS oncogene expression and activate tumor suppressor gene p53, resulting in cell differentiation and apoptosis. (NCI04)
A semi-synthetic analogue of Artemisinin - a sesquiterpene lactone extracted from the dry leaves of Artemisia Annua (sweet wormwood) used as anti-malaria agent. Limited data is available on Artemisinin antineoplastic activity.
A semisynthetic derivative of the nucleoside-like antineoplastic antibiotic spicamycin, originally isolated from the bacterium Streptomyces alanosinicus. KRN 5500 inhibits protein synthesis by interfering with endoplasmic reticulum and Golgi apparatus functions. This agent also induces cell differentiation and caspase-dependent apoptosis. (NCI04)
A weak tyrosine kinase inhibitor which has been used as a negative control analogue for Lavendustin A. (NCI)
An antibody-drug conjugate composed of the chimeric monoclonal antibody BR96 chemically linked to the cytotoxic drug doxorubicin. The antibody moiety of BMS-182248-1 binds to Lewis Y, a cell surface antigen expressed on many solid tumor types. Thus, the doxorubicin conjugate is targeted specifically to Lewis Y-expressing tumor cells, where it intercalates with DNA, thereby inhibiting DNA replication and repair, RNA synthesis and protein synthesis. (NCI)
A single chain chimeric protein consisting of a monoclonal antibody fragment attached to a portion of the Pseudomonas exotoxin A. LMB-7 immunotoxin attaches to B3, a Lewis Y-related carbohydrate epitope on some solid tumor cells. The antibody attaches to the cell and the exotoxin inhibits protein synthesis by inactivating elongation factor 2. (NCI04)
A second generation, long-lasting selective histamine H1 receptor antagonist with antiinflammatory property. Fexofenadine is a highly selective and reversible competitor at peripheral H1 histamine receptors in the gastrointestinal (GI) tract, blood vessels, and bronchial smooth muscle. This agent interferes with mediators release from mast cells either by inhibiting calcium ion influx across mast cell/basophil plasma membrane or by inhibiting intracellular calcium ion release within the cells. In addition fexofenadine may also inhibit the late-phase allergic reaction by acting on leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect. Overall, this agent blocks the actions of endogenous histamine, thereby leads to temporary relief of the negative symptoms associated with histamine and achieve effects such as decreased vascular permeability, reduction of pruritus and localized smooth muscle relaxation.
A water-soluble, tri-iodinated, non-ionic monomeric benzoate derivative and contrast medium used in diagnostic radiography. Upon administration, iobitridol is distributed through the vascular system and interstitial space. Like other organic iodine compounds, this agent blocks x-rays and appears opaque on x-ray film thus, enhancing the visibility of body parts containing this agent. Iobitridol is rapidly removed by the kidneys in an unchanged form, and in cases of renal failure, heterotropic excretion occurs via the biliary route.
A salicylic acid derivative with potential antineoplastic activity. Salirasib dislodges all Ras isoforms from their membrane-anchoring sites, thereby preventing activation of RAS signaling cascades that mediated cell proliferation, differentiation, and senescence. RAS signaling is believed to be abnormally activated in one-third of human cancers, including cancers of the pancreas, colon, lung and breast.
An extract from the myxobacteria Sorangium cellulosum that promotes tubulin polymerization and microtubule stabilization, thereby inhibiting mitosis. Epothilone A appears to be less potent than Epothilone B. (NCI)
A compound isolated from the myxobacterium Sorangium cellulosum. Similar to paclitaxel, patupilone induces microtubule polymerization and stabilizes microtubules against depolymerization conditions. In addition to promoting tubulin polymerization and stabilization of microtubules, this agent is cytotoxic for cells overexpressing P-glycoprotein, a characteristic that distinguishes it from the taxanes. Patupilone may cause complete cell-cycle arrest.
An orally active synthetic antifibrotic agent structurally similar to pyridine 2,4-dicarboxylate. Pirfenidone inhibits fibroblast, epidermal, platelet-derived, and transforming beta-1 growth factors, thereby slowing tumor cell proliferation. This agent also inhibits DNA synthesis and the production of mRNA for collagen types I and III, resulting in a reduction in radiation-induced fibrosis. (NCI04)
The active ingredient in a drug used to treat symptoms of asthma, such as trouble breathing, tight chest, wheezing, coughing, and runny nose. Montelukast blocks the action of a substance that causes airways in the lungs to narrow and causes other symptoms of asthma. It is a type of leukotriene receptor antagonist and a type of antiasthmatic agent.
A cell-permeable, selective mitogen-activated protein (MAP) kinase inhibitor which exhibits activity through the inhibition of the phosphorylation and activation of MAP kinase. (NCI)
A second-generation selective leukotriene B4 receptor (LTB4R) antagonist with potential antineoplastic activity. Although the exact underlying mechanism through which LY293111 exerts its effects has not been fully elucidated, this agent selectively binds to and blocks LTB4Rs, thereby inhibiting the downstream signalling pathway. LY29311 has been shown to induce apoptosis and inhibits cellular proliferation in LTB4R expressing cells, such as pancreatic cancer cells.
A bioreductive, alkylaminoanthraquinone prodrug with antineoplastic activity. Under hypoxic conditions, often seen in solid tumors, banoxantrone (AQ4N) is converted and activated by cytochrome P450 enzymes, which are upregulated in certain tumors, to the cytotoxic DNA-binding agent AQ4. Banoxantrone intercalates into and crosslinks DNA, and inhibits topoisomerase II. This results in an inhibition of DNA replication and repair in tumor cells. Combined with conventional therapeutic agents, both oxygenic and hypoxic regions of tumors can be targeted.
A cancer vaccine consisting of whole irradiated heterologous melanoma cells which express multiple melanoma-related antigens. Polyvalent melanoma vaccine may stimulate an antitumoral cytotoxic T-cell immune response in the host, resulting in inhibition of tumor cell proliferation and tumor cell death. (NCI04)
A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.
A piperazine and quinolone derivative that is used primarily as an antipsychotic agent. It is a partial agonist of SEROTONIN RECEPTOR, 5-HT1A and DOPAMINE D2 RECEPTORS, where it also functions as a post-synaptic antagonist, and an antagonist of SEROTONIN RECEPTOR, 5-HT2A. It is used for the treatment of SCHIZOPHRENIA and BIPOLAR DISORDER, and as an adjunct therapy for the treatment of depression.
A selective progesterone receptor modulator with anti-progesterone activity. Ulipristal binds to the progesterone receptor (PR), thereby inhibiting PR-mediated gene expression, and interfering with progesterone activity in the reproductive system. As a result, this agent may suppress the growth of uterine leiomyomatosis. Furthermore, by inhibiting or delaying ovulation and effecting endometrial tissue, ulipristal can be used as an emergency contraception.
Caudal regression syndrome is a disorder that impairs the development of the lower (caudal) half of the body. Affected areas can include the lower back and limbs, the genitourinary tract, and the gastrointestinal tract.In this disorder, the bones of the lower spine (vertebrae) are frequently misshapen or missing, and the corresponding sections of the spinal cord are also irregular or missing. Affected individuals may have incomplete closure of the vertebrae around the spinal cord, a fluid-filled sac on the back covered by skin that may or may not contain part of the spinal cord, or tufts of hair at the base of the spine. People with caudal regression syndrome can also have an abnormal side-to-side curvature of the spine (scoliosis). The spinal abnormalities may affect the size and shape of the chest, leading to breathing problems in some individuals.Individuals with caudal regression syndrome may have small hip bones with a limited range of motion. The buttocks tend to be flat and dimpled. The bones of the legs are typically underdeveloped, most frequently the upper leg bones (femurs). In some individuals, the legs are bent with the knees pointing out to the side and the feet tucked underneath the hips (sometimes called a frog leg-like position). Affected individuals may be born with inward- and upward-turning feet (clubfeet), or the feet may be outward- and upward-turning (calcaneovalgus). Some people experience decreased sensation in their lower limbs.Abnormalities in the genitourinary tract in caudal regression syndrome are extremely varied. Often the kidneys are malformed; defects include a missing kidney (unilateral renal agenesis), kidneys that are fused together (horseshoe kidney), or duplication of the tubes that carry urine from each kidney to the bladder (ureteral duplication). These kidney abnormalities can lead to frequent urinary tract infections and progressive kidney failure. Additionally, affected individuals may have protrusion of the bladder through an opening in the abdominal wall (bladder exstrophy). Damage to the nerves that control bladder function, a condition called neurogenic bladder, causes affected individuals to have progressive difficulty controlling the flow of urine. Genital abnormalities in males can include the urethra opening on the underside of the penis (hypospadia) or undescended testes (cryptorchidism). Females may have an abnormal connection between the rectum and vagina (rectovaginal fistula). In severe cases, both males and females have a lack of development of the genitalia (genital agenesis).People with caudal regression syndrome may have abnormal twisting (malrotation) of the large intestine, an obstruction of the anal opening (imperforate anus), soft out-pouchings in the lower abdomen (inguinal hernias), or other malformations of the gastrointestinal tract. Affected individuals are often constipated and may experience loss of control of bladder and bowel function.
The oils extracted from the leaves or bark of Cinnamomum verum. Cinnamon bark oil is used as a flavoring, in parfumary, and in medicinal preparations. Cinnamon leaf oil has similar uses but is often used for its industrial applications.
A common name for some Garcinia species, derived from a corruption of the word Cambodia, where the plant is found.
A topical anti-fungal agent. Acrisorcin is comprised of two active ingredients, 9-aminoacridine and 4-hexylresorcinol, but its clinical use has been discontinued.
A calcium salt form of mandelic acid, an aromatic alpha hydroxy acid used in the treatment of urinary tract infections and as an oral antibiotic.
A sulfonamide antibiotic used for topical application to the skin and the conjunctiva.
A substituted salicylamide with antimycotic activity, particularly against dermatophytes.
The calcium salt of undecylenic acid, an 11 carbon mono-unsaturated fatty acid with broad-spectrum antifungal activity. Undecylenic acid inhibits the morphogenesis of Candida albicans to its invasive fungal form and inhibits the conversion of unicellular yeast to their hyphal form.
The copper salt of undecylenic acid, an 11 carbon mono-unsaturated fatty acid with broad-spectrum antifungal activity. Undecylenic acid inhibits the morphogenesis of Candida albicans to its invasive fungal form and inhibits conversion of unicellular yeast to their hyphal form.
A natural or synthetic fungistatic fatty acid, antifungal Zinc Undecylenate is used topically in creams against fungal infections, eczemas, ringworm, and other cutaneous conditions. The zinc provides an astringent action, reducing rawness and irritation. (NCI04)
A calcium salt form of aminosalicylic acid, an analog of para-aminobenzoic acid (PABA) with antitubercular activity.
The sodium salt form of aminosalicylic acid, an analog of para-aminobenzoic acid (PABA) with antitubercular activity. Aminosalicylate sodium exerts its bacteriostatic activity against Mycobacterium tuberculosis by competing with PABA for enzymes involved in folate synthesis, thereby suppressing growth and reproduction of M. tuberculosis, eventually leading to cell death.
A sodium salt form of glucosulfone, an agent used to treat mycobacterial infections.
A muscarinic antagonist used to study binding characteristics of muscarinic cholinergic receptors.
The aluminum salt form of carbonic acid, an antacid with phosphate binding activity. Upon oral administration of aluminum carbonate, aluminum is able to bind to phosphate in the intestines, including the radionuclide phosphate P-32, thereby preventing phosphate uptake.
A live, attenuated viral vaccine to prevent yellow fever, endemic to parts of Africa and South America.
A dietary supplement containing all or most of the vitamins that may not be readily available in the diet. Vitamins may be classified according to their solubility either in lipids (vitamins A, D, E, K, F) or in water (vitamins C, B-complex). Present in minute amounts in various foods, vitamins are essential to maintaining normal metabolism and biochemical functions. (NCI04)
A pyrimidinedione-based diuretic. Aminometradine appears to inhibit the reabsorption of sodium ions by the renal tubules and is a relatively weak diuretic.
A pyrimidinedione-based diuretic and isomer of aminometradine with less toxicity.
The hydrochloride salt form of arginine, an essential amino acid in juvenile humans. Arginine is a complex amino acid, often found at active sites in proteins and enzymes due to its amine-containing side chain. Arginine may prevent or treat heart and circulatory diseases, combat fatigue, and stimulate the immune system. It also boosts production of nitric oxide, relaxing blood vessels, and treating angina and other cardiovascular problems. Arginine is also an important intermediate in the urea cycle and in detoxification of nitrogenous wastes. (NCI04)
movement of materials, usually across cell membranes, by processes not requiring metabolic energy expenditure.
chemical substances having a specific regulatory effect on the activity of a certain organ or organs; secreted by the inner part of the adrenal gland.
A hypersensitivity reaction resulting from the deposition of antigen-antibody immune complexes in tissues, which trigger activation of the complement system.
A condition where the retina contains no functional cone cells, so that in addition to the absence of color discrimination, vision in lights of normal intensity is difficult. [DDD:gblack, PMID:12015282]
Irregularly shaped, patchy discolorations in the skin.
An anatomic abnormality that is either present at birth or appears later in life.
An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation.
A type of xanthoma characterized by a nodular form. Tuberous xanthomas are firm subcutaneous nodules,whereby the overlying skin can have red or red-yellow color changes.
A malignant epithelial neoplasm characterized by the presence of a trabecular glandular architectural pattern.
Compounds that form soothing films on the surface of MUCOUS MEMBRANES. They are generally used as agents to protect the integrity of internal EPITHELIUM.
A type of cataract that is not apparent at birth but that arises in childhood or adolescence.
Abnormal SEX DIFFERENTIATION or congenital DISORDERS OF SEX DEVELOPMENT caused by abnormal levels of steroid hormones expressed by the GONADS or the ADRENAL GLANDS, such as in CONGENITAL ADRENAL HYPERPLASIA and ADRENAL CORTEX NEOPLASMS. Due to abnormal steroid biosynthesis, clinical features include VIRILISM in females; FEMINIZATION in males; or precocious sexual development in children.
A comedo in which the top of the pore is not stretched open and thus does not expose the clogged portion (which would appear black), hence the name whitehead.
A radiologic finding indicating the presence of bone destruction that results from the spread of cancer to the bone(s).
A non-neoplastic disorder characterized by a localized collection of histiocytes containing lipid. Xanthomas usually occur in the skin and subcutaneous tissues, but occasionally they may involve the deep soft tissues. -- 2003
A rare sarcoma arising from the meninges.
A B-cell non-Hodgkin lymphoma composed of large noncleaved cells. This is a subtype of diffuse large B-cell non-Hodgkin lymphoma.
A disease of cattle caused by bacteria of the genus BRUCELLA leading to abortion in late pregnancy. BRUCELLA ABORTUS is the primary infective agent.
A dissecting aneurysm in the portion of the descending aortic wall that is within the abdomen.
Erythrophagocytosis; phagocytosis of erythrocytes.
Bleeding in the orbital cavity that results in compression of orbital structures, resulting in ischemia of the optic nerve, and possible loss of vision.
A tooth from which the dental pulp has been removed or is necrotic. (Boucher, Clinical Dental Terminology, 4th ed)
A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.
A carcinoma arising from either the exocervical squamous epithelium or the endocervical glandular epithelium. The major histologic types of cervical carcinoma are: squamous carcinoma, adenocarcinoma, adenosquamous carcinoma, adenoid cystic carcinoma and undifferentiated carcinoma.
Any substance that inhibits xanthine oxidase, an enzyme that catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid, along with the generation of reactive oxygen species (ROS). Inhibition of xanthine oxidase can reduce the production of uric acid.
Acute hepatitis complicated by acute liver failure with hepatic encephalopathy occurring less than 8 weeks after the onset of jaundice.
Lactase is produced in the small intestine in humans, Lactase is a member of the beta-galactosidase family of enzymes, and hydrolyzes D-lactose to form D-galactose and D-glucose, which can be absorbed by the small intestine. There are many ways of assessing lactase activity. In one test, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a color reaction develops within 20 min as a result of hydrolyzed lactose (a positive result) in patients with normolactasia, whereas no reaction (a negative result) develops in patients with severe hypolactasia. Other, less direct, tests include the hydrogen breath test, and blood tests following lactose challenges.
Processes concerned with the synthesis, breakdown, and oxidation of carbohydrates in the tissues.
Frequency and quality of negative emotions, e.g., anger or hostility, expressed by family members or significant others, that often lead to a high relapse rate, especially in schizophrenic patients. (APA, Thesaurus of Psychological Index Terms, 7th ed)
A goiter that is not associated with functional thyroid abnormalities.
A radioisotope of the metal palladium used in brachytherapy implants or 'seed'. With a half-life of 17 days, palladium 103 administered with brachytherapy allows continuous, tumor-site specific low-energy irradiation to the tumor cell population while sparing normal adjacent tissues from radiotoxicity. (NCI04)
A radioactive isotope of the rare element ruthenium, a member of the light platinum group. A radioactive plaque containing ruthenium 106 may be inserted into the eye to irradiate ophthalmic tumors. (NCI04)
A high-grade metamorphic coal having a semimetallic luster, high content of fixed carbon, and high density, and burning with a short blue flame and little smoke or odor. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Hydrocarbon solvents with flash points above 38 degrees C
A hydrochloride salt form of dichlorophenarsine, an arsenic-containing agent formerly used in the treatment of syphilis.
The oil extracted from the foliage and wood of various conifers, especially Thuja occidentalis. Cedar oil is typically used for its aromatic properties.
The oil extracted from the fruit peel of Citrus limon. Lemon oil is used as a flavoring and for its aromatic qualities. It is also said to have many medicinal purposes.
The essential oil extracted from the needles and twigs of Pinus sylvestris. Pine oil is used for aromatherapy and for its antiseptic qualities in soaps and cleaning products.
The essential oil of Rosmarinus officinalis. Rosemary oil is used primarily for its aromatic properties.
The oil extracted from the bark of Croton eluteria. Cascarilla oil is used in the cosmetics and food industries for its fragrance and flavor.
The oil extracted from the seeds of Cuminum cyminum. Cumin oil is used in treatments of the digestive system.
Drugs that cannot be sold legally without a prescription.
The hydrochloride salt form of tripelennamine, an ethylenediamine derivative with an antihistaminergic property. Tripelennamine hydrochloride competitively blocks central and peripheral histamine H1 receptors, thereby limiting histamine's effects, including bronchoconstriction, vasodilation, increased capillary permeability, and spasmodic contractions of gastrointestinal smooth muscle. In addition, this agent binds to muscarinic receptors, resulting in anticholinergic activity.
The hydrochloride salt form of bromodiphenhydramine, a synthetic ethanolamine with histamine H1 antagonistic and sedative properties. Bromodiphenhydramine hydrochloride blocks the H1 histamine receptor and prevents the symptoms that are caused by histamine activity on capillaries, bronchial smooth muscle, and gastrointestinal smooth muscle, including vasodilation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastrointestinal smooth muscle. This drug also prevents histamine-induced pain and itching of mucous membranes.
An ethanolamine class of H1 antihistamines with mild antimuscarinic and sedative properties. Carbinoxamine diminishes the typical histaminergic effects on H1-receptors in bronchial smooth muscle, capillaries, and gastrointestinal smooth muscle, including vasodilation, bronchoconstriction, increased vascular permeability, pain, itching, and spasmodic contractions of gastrointestinal smooth muscle. Carbinoxamine maleate is used to provide symptomatic relieve of allergic symptoms.
The hydrochloride salt form of buclizine, a piperazine histamine H1 receptor antagonist with primarily antiemetic and antivertigo activities. Buclizine binds to and blocks the histamine H1 receptor, thereby preventing the symptoms that are caused by histamine activity. Buclizine exerts its anti-emetic effect by binding to and blocking the muscarinic and histamine receptors in the vomiting center of the central nervous system (CNS). This may prevent activation of the chemoreceptor trigger zone (CTZ) and may reduce nausea and vomiting.
A sodium salt form of nitrofurantoin, a synthetic derivative of imidazolidinedione (hydantoin) that inhibits bacterial DNA, RNA, and cell wall protein synthesis.
The isethionate salt form of hydroxystilbamidine, a cationic dye with antifungal, antitrypanosomal, antimalarial, and carcinostatic activities. Hydroxystilbamidine is able to bind to DNA and RNA in a non-intercalating manner, and is a powerful inhibitor of ribonucleases, thereby impeding cellular processes in protozoa. This agent was also shown to bind to lysosomes and induced a large number of lysosome-like bodies and secretion granules in trypanosome.
The sulfate salt form of codeine, a naturally occurring phenanthrene alkaloid and opioid agonist with analgesic, antidiarrheal and antitussive activity. Codeine sulfate mimics the actions of opioids by binding to the opioid receptors at many sites within the central nervous system (CNS). Stimulation of the mu-subtype opioid receptor stimulates the exchange of GTP for GDP on the G-protein complex and subsequently inhibits adenylate cyclase. This results in a decrease in intracellular cAMP and leads to a reduction in the release of neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline. The analgesic effect of codeine sulfate is likely due to its metabolite morphine, which induces opening of G-protein-coupled inwardly rectifying potassium (GIRK) channels and blocks the opening of N-type voltage-gated calcium channels, thereby resulting in hyperpolarization and reduced neuronal excitability.
The pamoate salt of imipramine, a synthetic dibenzazepine derivative with anti-depressant activity. Imipramine pamoate, a tricyclic antidepressant (TCA) potentiates the activity of adrenergic synapses by blocking the re-uptake of norepinephrine and serotonin, thereby preventing their degradation and increasing their availability. This drug also has antimuscarinic and anti-histamine properties, which contribute to its side effects.
The sulfate salt form of tranylcypromine, an orally bioavailable, nonselective, irreversible, non-hydrazine inhibitor of both monoamine oxidase (MAO) and lysine-specific demethylase 1 (LSD1/BHC110), with antidepressant and anxiolytic activities, and potential antineoplastic activities. Upon oral administration, tranylcypromine exerts its antidepressant and anxiolytic effects through the inhibition of MAO, an enzyme that catalyzes the breakdown of the monoamine neurotransmitters serotonin, norepinephrine, epinephrine and dopamine. This increases the concentrations and activity of these neurotransmitters. Tranylcypromine exerts its antineoplastic effect through the inhibition of LSD1. Inhibition of LSD1 prevents the transcription of LSD1 target genes. LSD1, a flavin-dependent monoamine oxidoreductase and a histone demethylase, is upregulated in a variety of cancers and plays a key role in tumor cell proliferation, migration, and invasion.
The hydrochloride salt of trifluoperazine, a phenothiazine derivative and a dopamine, alpha-adrenergic, and anticholinergic antagonist with antipsychotic, anxiolytic, and antiemetic activities. Trifluoperazine blocks central dopamine receptors, which may prevent or mitigate delusions and hallucinations caused by an excess of dopamine; dopamine blockade in the chemoreceptor trigger zone (CTZ) may result in an antiemetic effect. This agent binds to central adrenergic receptors, which may result in anxiolytic effects. Trifluoperazine also functions as a calmodulin inhibitor, elevating cytosolic calcium.
The hydrochloride salt form of thiothixene, a thioxanthene derivative and a dopamine antagonist with antipsychotic property. Thiothixene blocks postsynaptic dopamine receptors in the mesolimbic system and medullary chemoreceptor trigger zone, thereby decreasing dopamine activity leading to decreased stimulation of the vomiting center and psychotic effects, such as hallucinations and delusions. In addition, this agent blocks the D2 somatodendritic autoreceptor, thereby increasing dopamine turnover. Thiothixene possesses weak affinity for the histamine H1 and alpha-adrenergic receptors.
a chemical agent such as caffeine, that temporarily arouses or accelerates physical activity
The hydrochloride salt form of oxyphencyclimine, a synthetic tertiary amine and antimuscarinic agent with antispasmodic and antisecretory activities. Oxyphencyclimine binds to and blocks the muscarinic receptor on smooth muscle. This agent has a direct relaxing effect on smooth muscle and therefore prevents spasms in the muscles of the gastrointestinal tract, inhibits gastrointestinal propulsive motility, decreases gastric acid secretion and controls excessive pharyngeal, tracheal and bronchial secretion.
The bitartrate salt form of phenylephrine, a direct-acting sympathomimetic amine chemically related to adrenaline and ephedrine with potent vasoconstricting activity. Phenylephrine is a post-synaptic alpha-adrenergic receptor agonist that causes vasoconstriction, increases systolic/diastolic pressures, reflex bradycardia, and increases stroke output.
The hydrochloride salt form of pseudoephedrine, a phenethylamine and an diastereomer of ephedrine with sympathomimetic property. Pseudoephedrine hydrochloride displaces norepinephrine from storage vesicles in presynaptic neurones, thereby releasing norepinephrine into the neuronal synapses where it stimulates primarily alpha-adrenergic receptors. It also has weak direct agonist activity at alpha- and beta- adrenergic receptors. Receptor stimulation results in vasoconstriction and decreases nasal and sinus congestion.
The sulfate salt form of pseudoephedrine, a phenethylamine and a diastereomer of ephedrine with sympathomimetic property. Pseudoephedrine sulfate displaces norepinephrine from storage vesicles in presynaptic neurones, thereby releasing norepinephrine into the neuronal synapses where it stimulates primarily alpha-adrenergic receptors. It also has weak direct agonist activity at alpha- and beta- adrenergic receptors. Receptor stimulation results in vasoconstriction and decreases nasal and sinus congestion.
The hydrochloride salt of Dyclonine, an unclassified compound with local anesthetic effect. Dyclonine reversibly binds to activated sodium channels on the neuronal membrane, thereby decreasing the neuronal membrane's permeability to sodium ions, leading to an increased threshold for excitation. This reversibly stabilizes the membrane and inhibits depolarization, leading to the failure of a propagated action potential and subsequent conduction blockade. This results in a transient and reversible loss of sensation in a localized area of the body.
A liquid composed of two immiscible substances, typically some form of fat and water. In parenteral nutrition, a fat emulsion may contain phospholipids, triglycerides and essential fatty acids (NCI04)
The sodium salt form of chlorothiazide, a short-acting, benzothiadiazinesulfonamide derivative belonging to the class of thiazide diuretics. Chlorothiazide is excreted unchanged by the kidneys.
A subclass of diuretics that limits the secretion of POTASSIUM into the URINE.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.
Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.
Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS.
A substance used to make drugs that are used to treat several heart conditions, including congestive heart failure. Digitalis is made from the dried leaves of Digitalis purpurea (common foxglove) plants. It is a type of cardiac glycoside.
The hydrochloride salt form of methyldopa, a phenylalanine derivate and aromatic amino acid decarboxylase inhibitor with antihypertensive activity. Methyldopa is a prodrug and is metabolized in the central nervous system. The antihypertensive action of methyldopa seems to be attributable to its conversion into alpha-methylnorepinephrine, which is a potent alpha-2 adrenergic agonist that binds to and stimulates potent central inhibitory alpha-2 adrenergic receptors. This results in a decrease in sympathetic outflow and decreased blood pressure.
The hydrochloride salt form of glutamic acid, a non-essential amino acid. Used as a gastric acidifier, glutamic acid hydrochloride releases hydrochloric acid into the stomach, thereby lowering gastric pH. (NCI)
The hydrochloride salt form of naftifine, an allylamine derivate with synthetic broad-spectrum antifungal activity. Although the exact mechanism through which naftifine hydrochloride exerts its effect is unknown, it appears to selectively inhibit the enzyme squalene 2,3-epoxidase, thereby inhibiting the biosynthesis of sterol. This results in a decreased amount of sterols, especially ergosterol which is the primary fungal membrane sterol, and a corresponding accumulation of squalene in fungal cells. Naftifine hydrochloride can be fungicidal as well as fungistatic to yeasts depending on the concentration and the organisms involved.
Medications used to treat lice and scabies infestations.
Any synthetic steroid derivative exhibiting the same function as the naturally occurring corticosteroid hormone, formulated for topical application. Topical corticosteroids are applied to the skin where it exerts its effect, however, corticosteroids can be absorbed systemically after being applied locally. Topical corticosteroids are mainly used for the localized treatment of inflammation of the skin and help relieve symptoms such as itching, swelling and redness.
A synthetic glucocorticoid with anti-inflammatory and immunosuppressive properties. Like other glucocorticoids, diflorasone enters the cell by diffusion across the cell membrane and binds to the glucocorticoid receptor (GR) in the cytoplasm. The receptor complex subsequently translocates to the nucleus and activates or represses genes by interacting with short, palindromic DNA sequences called glucocorticoid response element (GRE). Gene activation leads to the exertion of anti-inflammatory effects, e.g. upregulation of IkappaB, while gene repression inhibits production of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-2 and IL-6, thereby preventing activation of cytotoxic T-lymphocytes.
The hydrochloride salt form of apraclonidine, a clonidine derivative with selective alpha-2-adrenergic agonistic property. When administered directly to eyes, apraclonidine hydrochloride enhances aqueous humor outflow and decreases aqueous production by vasoconstriction. It is used mostly in ophthalmic preparations for decreasing intraocular pressure.
The sodium salt form of flurbiprofen, a propionic acid derivative and a member of the phenylalkanoic acid group of non-steroidal antiinflammatory drugs (NSAIDs) with analgesic, antiinflammatory and antipyretic effects. Flurbiprofen non-selectively binds to and inhibits cyclooxygenase (COX). This results in a reduction of arachidonic acid conversion into prostaglandins that are involved in the regulation of pain, inflammation and fever. This NSAID also inhibits carbonic anhydrase, thereby reducing the production of hydrogen and bicarbonate ions. Upon ocular administration, flurbiprofen may reduce bicarbonate ion concentrations leading to a decrease in the production of aqueous humor, thereby lowering intraocular pressure.
The sodium salt of acetazolamide, a nonbacteriostatic sulfonamide derivative with diuretic and anticonvulsant properties. Acetazolamide is a potent inhibitor of carbonic anhydrase that plays an important role in the control of fluid secretion. Inhibition of this enzyme in the kidney results in a reduction in the availability of hydrogen ions for active transport in the renal tubule lumen, thereby leading to increased bicarbonate and cation excretion, and increased urinary volume. Reduced bicarbonate level in circulation induces reduction of intraocular pressure via osmotic mechanism. The anticonvulsant activity of acetazolamide may contribute to inhibition of carbonic anhydrase in the CNS, which decreases carbon dioxide tension in the pulmonary alveoli, thus increasing arterial oxygen tension.
Insulin formulations that contain substances that retard absorption thus extending the time period of action.
The oil obtained from the livers of several species of shark. Shark liver oil is used as a dietary supplement and may have immunostimulating properties.
The oil extracted from the liver of Hippoglossus species. Halibut liver oil is taken as a supplement for vitamins A and D.
The orally bioavailable delta form of the naturally-occurring fat-soluble vitamin E, mostly found in soybean and corn oils, with potential antioxidant activity. Although the exact mechanism of action of this tocopherol has yet to be fully identified, delta-tocopherol appears to have the ability to scavenge free radicals, thereby protecting cells against oxidative damage.
Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and BILIRUBIN, and of XENOBITOICS in the blood.
Category of human frozen plasma products, regardless of time from donation to freezing
A radiopharmaceutical providing radioactive chromium-51 in the form of sodium chromate for diagnostic usage. Upon dissociation, the chromate ion binds to the membrane of red blood cells. Following translocation across the cell membrane, the ion binds to intracellular hemoglobin, thereby allowing imaging to determine red blood cell volume, survival time and evaluate blood loss.
A radiopharmaceutical containing the radioisotope I-123 with diagnostic property. After absorption, the iodide is distributed through the extracellular fluid of the body and accumulates in the thyroid gland, thereby allowing measurement of thyroid function.
A sterile, intramuscular suspension of alum (aluminum potassium sulfate)-precipitated toxoids indicated for active immunization for the prevention of tetanus and diphtheria for use in persons 7 years of age or older.
A preparation of formaldehyde-deactivated toxin isolated from the bacterium Clostridium tetani. Tetanus toxoid is used for booster injection and can stimulate the production of antitoxin antibodies. This agent may be used as an adjuvant in cancer vaccines.
An polyvalent vaccine used to prevent infection by the bacterium Streptococcus pneumoniae. Pneumococcal polyvalent vaccine contains highly purified capsular antigens from the 23 most prevalent or invasive pneumococcal types of Streptococcus pneumoniae to ensure cross-protection. Following vaccination, protective capsular type-specific antibody levels typically develop by the third week; serotype-specific antibody levels generally decline after 5-10 years.
Vaccines or candidate vaccines used to prevent MAREK DISEASE, an avian disease caused by a herpesvirus.
Erysipelothrix rhusiopathiae serological reagents are devices that consist of antigens and antisera used in serological tests to identify Erysipelothrix rhusiopathiae from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of disease caused by this bacterium belonging to the genus Erysipelothrix. This organism is responsible for a variety of inflammations of the skin following skin abrasions from contact with fish, shellfish, or poultry.
The dietary practice of completely avoiding meat or fish products in the DIET, consuming VEGETABLES, CEREALS, and NUTS. Some vegetarian diets called lacto-ovo also include milk and egg products.
A congenital abnormality characterized by the presence of a continuous layer of skin extending over the eyeballs and the absence of eyelids and the palpebral fissure.
Acute infection of the bile ducts caused by bacteria ascending from the small intestine.
Excessive fat around the stomach and abdomen.
A systemic disease, often associated with arthritis, fever, and weight loss. The cutaneous lesions consist of histiocytes, which are usually confined to the dermis. A large number of patients develop malignant tumors (carcinomas, sarcomas, and lymphomas). --2003
A nerve inflammation in the foot caused by chronic compression of the plantar nerve between the METATARSAL BONES.
This form of fleck retina disease (see 228980) is characterized by discrete uniform white dots over the entire fundus with greatest density in the midperiphery and no macular involvement. Night blindness occurs. Both autosomal dominant and autosomal recessive inheritance had been suggested (Krill and Folk, 1962; Krill, 1977).
A hypercoaguable state that results from the presence of the immunoglobulin known as Lupus Anticoagulant. The antibody interacts with cell membrane phospholipids, causing increased aggregation and adhesion of platelets, which causes increased clot formation. Though the majority of patients who test positive for lupus anticoagulant do not have lupus, those individuals afflicted with lupus have a higher probability of developing the antibody.
A bacterial infection that is transmitted from animals to people.
An intestinal infection with Isospora belli.
Objective evidence of disease perceptible to the examining healthcare provider.
leg pain and weakness brought on by walking
A secreted KAZAL MOTIF-containing serine peptidase inhibitor that inhibits TRYPSIN. It is a protein composed of 56 amino acid residues and is different in amino acid composition and physiological activity from the Kunitz bovine pancreatic trypsin inhibitor (APROTININ). It protects against the trypsin-mediated premataure activation of ENZYME PRECURSORS in the PANCREAS. Mutations in the SPINK1 gene are associated with CHRONIC PANCREATITIS.
Refers to those amino acids that your body can create out of other chemicals found in your body.
Abnormally high level of bilirubin in the blood. Excess bilirubin is associated with jaundice.
Involuntary loss of urine associated with overdistention of the bladder.
Symptoms of NAUSEA and VOMITING in pregnant women that usually occur in the morning during the first 2 to 3 months of PREGNANCY. Severe persistent vomiting during pregnancy is called HYPEREMESIS GRAVIDARUM.
Pathological persistent sexual disinhibiting behavior, directed at oneself or to others. [ICM:PCaroppo]
The presence of two or more genetic loci on the same chromosome. Extensions of this original definition refer to the similarity in content and organization between chromosomes, of different species for example.
Harmless or beneficial population of microorganisms or plant life that normally occur in specific areas of the body or the environment.
A species of STAPHYLOCOCCUS found on the skin of humans (and non-human primates), often causing hospital-acquired infections (CROSS INFECTION).
A species of facultatively anaerobic, Gram positive, cocci shaped bacteria in the phylum Firmicutes. This species is positive for catalase and urease and negative for oxidase, alkaline phosphatase and coagulase. It can ferment sucrose, mannitol, fructose, and lactose but not arabinose, cellobiose, turanose, xylose, or xylitol. S. simulans is found on human and animal skin and is a pathogen that can cause bumble foot disease and mastitis in animals and ostomyelitis and prosthesis related infections in humans.
Having been subjected to inspection or evaluation.
Admitting diagnosis are the diagnoses documented for administrative purposes as the basis for a hospital admission.
Diagnosis of a disease or condition made after DEATH.
The potential future harm that may arise from some present action or attribute or condition is almost certain.
A response indicating that something is or was difficult.
Posing no difficulty; requiring little effort.
A primary tumor TNM finding indicating that the status of the primary tumor cannot be assessed.
A general term that refers to a TNM finding of cancer metastases in multiple lymph nodes. The definition of N4 TNM finding depends on the specific type of cancer that it refers to; for example, for ocular adnexal lymphoma it refers to metastases to central lymph nodes.
No morphologic evidence of primary tumor, in accordance with TNM classification system guidelines.
A pathologic primary tumor TNM stage finding. The definition of pT1 stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pT1 stage finding is defined as follows: cancer with tumor size 2.0 cm or less in greatest dimension; for colorectal cancer, pT1 stage finding is defined as follows: cancer with invasion into the submucosa. (from AJCC 6th and 7th Eds.)
A pathologic primary tumor TNM stage finding. The definition of pT2 stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pT2 stage finding is defined as follows: cancer with tumor size more than 2.0 cm, but not more than 5.0 cm in greatest dimension; for colorectal cancer, pT2 stage finding is defined as follows: cancer with invasion into the muscularis propria. (from AJCC 6th and 7th Eds.)
A pathologic primary tumor TNM stage finding. The definition of pT3 stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pT3 stage finding is defined as follows: cancer with tumor size more than 5.0 cm in greatest dimension; for kidney cancer, pT3 stage finding is defined as follows: cancer with tumor extending into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota's fascia. (from AJCC 7th Ed.)
No morphologic evidence of regional lymph node metastasis by routine histologic staining, in accordance with TNM classification system guidelines.
A pathologic regional lymph nodes TNM stage finding. The definition of pN2 stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pN2 stage finding is defined as follows: cancer with metastases in 4 to 9 axillary lymph nodes, or metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases. ""Clinically detected"" is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination; for colorectal cancer, pN2 stage finding is defined as follows: cancer with metastasis in four or more regional lymph nodes. (from AJCC 7th Ed.)
No morphologic evidence of distant metastasis, in accordance with TNM classification system guidelines.
The process of the diffusion or accumulation in a tissue or cells of a substance not normal to it or in amounts above normal. (NCI)
A plaque (a solid, raised, plateau-like (flat-topped) lesion greater than 1 cm in diameter) with a red or reddish color often associated with inflammation or irritation. []
A change resulting in a consistency that is different from the original.
The quality of being hard, the process of hardening, or an abnormally hard spot or place, particularly of the skin.
A finding indicating the tendency of a tissue sample or solid substance to break into small pieces under pressure or contact.
A morphologic finding indicating reduced tissue density.
A circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point.
A change in color that deviates from the norm or outwith the bounds of what is considered normal.
A flat lesion characterized by change in the skin color.
A constellation of signs and symptoms caused by an excess of glucocorticoids. Classic features include moon facies, buffalo hump, obesity, striae and adiposity.
This is a description previously used to describe a facial form characterized by a short, upturned nose, wide mouth, widely spaced eyes, and full cheeks. Because of the imprecision in this definition it is preferable to describe these features precisely. This term is retained because it was often used in the past, but it should not be used for new annotations.
A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness.
A bone fracture that is taking an abnormally long time to heal.
Abnormal separation of bones, often from a LIGAMENT.
Abnormal tissue formation due to abnormal cellular organization, which may result in a morphologic defect.
Fusion, stoppage, or loss of patency occuring before the usual or proper time.
One or more flexion contractures (a bent joint that cannot be straightened actively or passively) that are present at birth.
A finding indicating the presence of greater than normal asymmetry between the right and left sides of the body. The asymmetry may be manifested in the entire side or part of it.
congenital defects of closure of one or more vertebral arches, which may be associated with malformations of the spinal cord, nerve roots, congenital fibrous bands, lipomas, and congenital cysts.
An abnormal, epithelial-lined connection between an artery and vein that is present at the time of birth.
An embryological structure that is retained past the usual embryonic stage.
Renal calculi with a characteristic shape like antlers of a deer, formed as it extends into multiple calices of the RENAL PELVIS. A large number of staghorn calculi as well as other URINARY CALCULI are composed of STRUVITE.
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. [HPO:probinson]
Elongated, spindle-shaped dilation in the wall of blood vessels, usually large ARTERIES with ATHEROSCLEROSIS.
An aneurysm that is located within the system of small blood vessels, including capillaries, venules, and arterioles, that perfuse the body's tissues.
A comedo in which the part of the pore at the surface of the skin is stretched and open, exposing the contents of the comedo, which appear black.
a state in which the normal flow of a body liquid stops
The presence of gas in an anatomical location where it is not normally found.
Benign, congenital, neuroepithelial cysts that are typically filled with a viscous mucus. They usually arise in the anterior portion of the THIRD VENTRICLE between the fornices.
recurrent stenosis; occurs usually after corrective surgery to the orifice of a heart valve.
Swelling due to excessive accumulation of fluid under the skin defined by a persistent indentation when pressure is applied to the swollen area. Causes include systemic conditions (e.g., heart failure, liver failure, or kidney failure) and local conditions affecting the extremities.
A small (less than 1 cm) fluid-filled lesion, raised above the plane of surrounding skin
The leaking of serosanguinous fluids from an orifice or wound.
Pus-containing fluid that is draining from an orifice or wound.
Extravasation of blood into the arterial wall following a tear in the intima and leading to separation of the layers of the wall.
An ulcer of the colon due to pressure and irritation from retained fecal masses.
An INFLAMMATION of the MUCOSA with burning or tingling sensation. It is characterized by atrophy of the squamous EPITHELIUM, vascular damage, inflammatory infiltration, and ulceration. It usually occurs at the mucous lining of the MOUTH, the GASTROINTESTINAL TRACT or the airway due to chemical irritations, CHEMOTHERAPY, or radiation therapy (RADIOTHERAPY).
A morphologic finding indicating the presence of neutrophils and/or eosinophils in a tissue sample.
Accumulation of polymorphonuclear neutrophils in the mucosal crypts of the colon. It occurs in ulcerative colitis.
The coexistence of a chronic inflammatory process with a superimposed polymorphonuclear neutrophilic infiltration.
A morphologic finding referring to the presence of a cellular infiltrate that is composed of non-neoplastic or neoplastic lymphocytes in a tissue sample.
A cystic inflammatory lesion that is comprised of fluids, lipids, and cholesterol crystals, and which is surrounded by a fibrous lining.
A lump of extravasated sperm in the paratesticular region in men who have undergone vasectomy.
A granuloma that is not associated with necrotic changes. The majority of cases are of non-infectious origin. Causes include sarcoidosis, hypersensitivity pneumonitis, drug reactions, and Crohn disease.
A process of tissue replacement where the tissue is being replaced by hyaline or the tissue has degenerated to hyaline.
Eosinophilic hyaline ovoid bodies which are often found in the subepidermal papillary regions or sometimes in the epidermis. Civatte bodies (CBs) are seen as rounded, homogenous, eosinophilic masses on routine H and E staining lying in the deeper parts of epidermis/epithelium and more frequently in dermis/connective tissue. They are known as CBs (in epithelium/epidermis), colloid bodies, or hyaline bodies (in connective tissue). They are 10-25 micrometers in diameter and situated mostly within or above the inflammatory cell infiltrate. In lichen planus, the number of necrotic keratinocytes may be so large that they are seen lying in clusters in the uppermost dermis. These bodies show a positive periodic acid Schiff reaction and are diastase resistant
Degenerative changes in elastic tissues.
Yellow-colored streaks, patches, or spots on the intimal surface of arteries. Fatty streaks stain red with Sudan III or Sudan IV. [PMID:8181179]
A morphologic finding referring to the presence of necrosis that is confined to a specific anatomic zone. Representative example is the hepatic zonal necrosis that affects the hepatic parenchyma either in the portal areas or around the hepatic veins.
The destruction of tumor cells or a reduction in swelling.
An area of pseudoinfarction with congestion and parenchymal atrophy but no infarction
Brain infarction that affects small subcortical vessels due to occlusion of a penetrating artery deep in the brain. It may lead to lacunar stroke.
Small hyaline masses of degenerated cells that develop into compact concretions due to pressure dehydration and/or compaction of dead cells. May appear mineralized.
Deposition of cholesterol in the skin. It appears as a slightly elevated and yellow bump usually in the skin around the eyes.
Calcium deposits in degenerated or necrotic tissue without abnormalities in blood calcium.
Any weakening or degeneration, especially through lack of use.
Undergrowth of the limbs that affects only one side.
A type of nuclear polyploidization in which multiple cycles of DNA REPLICATION occur in the absence of CELL DIVISION and result in a POLYPLOID CELL.
The possession of four chromosomes of any one type in an otherwise diploid cell.
A chromosomal abnormality in which a somatic cell is missing a single member of one or more pairs of homologous chromosomes.
A very rare congenital syndrome characterized by the presence of three haploid sets of chromosomes. The surviving infants have multiple severe birth defects.
A numerical chromosomal abnormality characterized by the presence of four complete sets of chromosomes.
A chromosome inversion involving a segment that includes the centromere.
A chromosome inversion involving a segment that does not include the centromere.
An abnormal chromosome with two centromeres as opposed to the normal one centromere.
A translocation in which the centromeres of two chromosomes are fused, forming a chromosome consisting of the long arms of two different chromosomes. -- 2003
Degeneration of the cell nucleus marked by contraction of the chromatin into small pieces and loss of the nuclear boundary.
The phagocytic destruction of nerve cells.
A morphologic finding indicating the presence of Mallory bodies in the liver parenchyma. Mallory bodies are eosinophilic cytoplasmic inclusions in the hepatocytes. They contain filaments and are present in the liver parenchyma of patients with various liver disorders including alcoholic liver disease, Wilson disease, and primary biliary cirrhosis.
A round basophilic inclusion body that contains calcium and iron. It is found in the bladder wall of patients with malakoplakia.
Ring fibers are formed by a bundle of peripheral myofibrils which are circumferentially oriented such that they encircle the internal portion of the sarcoplasm which is normal in structure and orientation.
Giant platelets are larger than 7 micrometers and usually 10 to 20 micrometers. The term giant platelet is used when the platelet is larger than the size of the average red cell in the field. (Description adapted from College of American Pathologists, Hematology Manual, 1998).
A general term for the abnormal growth of squamous cells on the surface of the cervix. The changes in the cells are described as low grade or high grade, depending on how much of the cervix is affected and how abnormal the cells appear.
A precancerous neoplastic process characterized by the presence of moderate or severe dysplastic cytological changes which extend to the upper part of the squamous epithelium. Maturation at the surface of the squamous epithelium may or may not be present. Representative examples include the high grade esophageal squamous intraepithelial neoplasia, high grade cervical squamous intraepithelial neoplasia, high grade vaginal intraepithelial neoplasia, and high grade vulvar intraepithelial neoplasia.
A microscopic finding indicating the presence of an atypical neoplastic cellular infiltrate with cytologic characteristics and/or architectural patterns that are not diagnostic, but raise the possibility of malignancy.
An abnormality often noted in pap smears. Koilocytotic atypia affects the squamous epithelium of the transformation zone. The cells involved show cytoplasmic vacuolization that might be related to their ability to store glycogen. The most characteristic feature of this condition is the peripheral cytoplasmic condensation associated with an increase of tonofilaments. (from Acta Cytol 1981;25:377-82)
An increase in the size of a cellular nucleus.
A morphologic finding referring to the presence of darkly stained nuclei due to abundance of DNA on hematoxylin-eosin stained sections. It is suggestive of malignancy.
An anemic condition which results from a lack hemoglobin within erythrocytes.
A benign (not cancer) condition in which cells look abnormal under a microscope and are increased in number.
Solitary or multiple benign hepatic vascular tumors, usually occurring in women of 20-50 years of age. The nodule, poorly encapsulated, consists of a central stellate fibrous scar and normal liver elements such as HEPATOCYTES, small BILE DUCTS, and KUPFFER CELLS among the intervening fibrous septa. The pale colored central scar represents large blood vessels with hyperplastic fibromuscular layer and narrowing lumen.
A polyp found mainly in the stomach and colon. Microscopically, it is characterized by elongated, serrated crypts lined by proliferative epithelium. Hyperplastic polyps are traditionally considered non-neoplastic, but ras mutation is common, clonality has been demonstrated and biochemical abnormalities and epidemiological associations that occur in colorectal adenomas and carcinomas have been found (WHO Tumors of the Digestive System, 2000).
A benign lesion characterized by epidermal and adnexal epithelial hyperplasia. It is caused by chronic inflammation and infection. It may be associated with cutaneous neoplasms as well.
A pathologic hyperplastic process characterized by the proliferation of the cells of the epithelial layer that resemble the basal cells of the lower part of the epidermis.
An acanthoma characterized by the presence of psoriasiform epidermal acanthosis and basal cells with pale cytoplasm.
A benign or malignant, diffuse and/or follicular lymphocytic proliferation.
Proliferation of the glandular epithelial cells.
Proliferation of glandular epithelial cells associated with the presence of cytologic atypia and architectural growth pattern changes.
A skin condition characterized by excessive development of keratin in hair follicles, resulting in rough, cone-shaped, elevated papules resulting from closure of hair follicles with a white plug of sebum.
Seborrheic keratosis that arises from follicular structures in the skin. It presents as a solitary nodule in the skin and is characterized by the presence of prominent squamous eddies.
A morphologic finding indicating the alteration of the squamous or transitional epithelial cells to glandular cells.
A morphologic finding indicating the alteration of the glandular acinar epithelial cells to apocrine sweat gland cells.
A morphologic finding indicating the replacement of epithelial tissue outside the intestines by intestinal-type epithelium.
A reactive metaplastic change in the urinary tract epithelium. The metaplastic changes in the epithelium resemble renal tubular structures. It can occur following surgical procedures, inflammation, stone formation, or trauma.
Heterotopic formation of normal bone within soft tissue.
A usually neoplastic transformation of the cell, associated with altered architectural tissue patterns. The cellular changes include nuclear and cytoplasmic abnormalities. Molecular genetic abnormalities are also often found and, in some instances, may lead to cancer.
A morphologic finding indicating the presence of mild cellular atypia associated with mild architectural changes in a tissue sample.
A morphologic finding indicating the presence of moderate cellular atypia associated with moderate architectural changes in a tissue sample.
A morphologic finding indicating the presence of severe cellular atypia associated with severe architectural changes in a tissue sample.
Any disease or disorder of a gland, characterized by abnormal development or enlargement of the gland.
Breast fibrocystic change characterized by the presence of epithelial cell hyperplasia. Epithelial atypia is present.
A precancerous neoplastic process that affects the squamous, glandular, or transitional cell epithelium without evidence of invasion. It is characterized by the presence of mild epithelial dysplasia.
A rare, usually solitary, benign epithelial tumor of the skin that appears to arise from a hair follicle. It usually develops in the head and neck region as a nodular lesion with a central keratotic plug.
A tumor histologically indistinguishable from, but larger than, benign fibrous histiocytoma of bone. It usually arises from the metaphysis of long bones.
Epidermal nevi are congenital lesions that affect about 1 in 1,000 people. They appear at or shortly after birth as localized epidermal thickening with hyperpigmentation that frequently follow the lines of Blaschko, suggesting that they result from postzygotic somatic mutation in the skin (Paller et al., 1994). A rare subgroup of epidermal nevi is clinically indistinguishable from other epidermal nevi, but displays histopathologic features typical of epidermolytic hyperkeratosis (see EHK, 113800), and patients with this type of epidermal nevi sometimes have offspring with generalized EHK (Paller et al., 1994). Woolly hair nevus is a rare condition characterized by the development of woolly hair in a restricted area on the scalp, either present at birth or becoming evident later in life when scalp hair begins to grow. Woolly hair nevus can be an isolated finding or can occur in association with additional ectodermal defects; epidermal nevi have been reported in association with woolly hair nevi (summary by Ramot and Zlotogorski, 2015). Nevus sebaceous, a benign congenital skin lesion that preferentially affects the scalp and face, is characterized by hairless, yellow-orange plaques of various size and shape. Histology shows that nevus sebaceous is a hamartoma consisting of epidermal, sebaceous, and apocrine elements. About 24% of nevi develop secondary tumors, some of which may be malignant (summary by Groesser et al., 2012). Also see giant pigmented hairy nevus (137550) and malignant melanoma (155600).
A hamartoma characterized by localized malformation of one or more of the components of the dermis; presenting as clustered, slightly raised, pea-sized lesions distributed over the abdomen, back, buttocks, arms, or thighs. It may be an isolated lesion or a component of one of a number of inherited disorders, such as tuberous sclerosis.
A polyp characterized by an overgrowth of mature cells and tissues that normally occur in the affected area.
Thickening of the tunica intima of a blood vessel due to injury.
A lymphangioma affecting several anatomic sites.
Dysplastic papular lesions presenting on the genitalia of either sex. The lesions are associated with human papillomavirus infection. The majority of cases have a benign clinical course, although, a small number of cases with malignant transformation have been reported.
The development of numerous polyps (growths that protrude from a mucous membrane).
A multinodular intermediate fibroblastic neoplasm that arises from soft tissue or viscera, in children and young adults. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes, and plasma cells.
Multiple subcutaneous non-fragile and skin-coloured papules characterized by interstitial infiltrate of spindle and epithelioid histiocytes, and mucin. There are well circumscribed aggregates of epithelioid histiocytes and mucin in the upper and middle dermis,with the histiocytes arranged between collagen bundles and separated from the epidermis by a Grenz zone.
A malignant neoplasm in which the examined tissue can not be determined with certainty if it represents the primary site of tumor growth or tumor spread from another anatomic site.
A malignant neoplasm characterized by the presence of small atypical cells.
A malignant neoplasm characterized by then presence of atypical giant cells.
A malignant neoplasm characterized by the presence of atypical spindle cells.
A neoplasm arising from the epithelial cells. It is characterized by the absence of morphologic features associated with malignancy (severe cytologic atypia, tumor cell necrosis, and high mitotic rate). Benign epithelial neoplasms remain confined to the original site of growth and only rarely metastasize to other anatomic sites.
A usually aggressive malignant epithelial neoplasm composed of cells with significant cytologic atypia and nuclear pleomorphism.
A malignant epithelial neoplasm composed of giant, pleomorphic cells and spindle cells.
A malignant epithelial neoplasm composed of atypical polygonal cells with a large amount of eosinophilic cytoplasm. A representative example is the fibrolamellar hepatocellular carcinoma.
A tiny localized pulmonary nodule characterized by neuroendocrine cell proliferation. It is usually discovered as an incidental finding during routine histologic examination of tissue sections or during radiologic examination.
A neuroendocrine carcinoma composed of malignant fusiform small cells.
A neuroendocrine carcinoma composed of malignant small cells of intermediate shape.
An epithelial neoplasm with a papillary growth pattern in which the malignant cells are confined to the epithelium, without evidence of invasion.
A benign epithelial neoplasm characterized by a papillary growth pattern, lack of significant cytologic atypia, and a wart-like appearance.
A well differentiated squamous cell carcinoma characterized by a papillary, exophytic growth pattern and hyperkeratosis. The most commonly affected anatomic sites are the larynx, penis, cervix, vagina, and vulva.
A malignant epithelial neoplasm confined to the squamous epithelium, without invasion of the underlying tissues.
A squamous cell carcinoma which has spread from its original site of growth to another anatomic site.
Squamous cell carcinomas with morphologically prominent production of keratin.
A squamous cell carcinoma composed of large atypical cells, without morphologic evidence of keratin production.
A squamous cell carcinoma composed of small atypical cells, without morphologic evidence of keratin production.
A squamous cell carcinoma characterized by the formation of gland-like structures.
A malignant epithelial neoplasm involving all the layers of the squamous epithelium, but it is not certain if it is confined to the squamous epithelium or it has invaded the basement membrane and the underlying stroma.
A squamous cell carcinoma with minimal stromal invasion.
A nonkeratinizing carcinoma which occurs predominantly in the nasopharynx but also in the tonsils and rarely in other anatomic sites. It is characterized by the presence of large malignant cells with vesicular nuclei, prominent nucleoli, syncytial growth pattern, and a lymphoplasmacytic infiltrate.
A superficial basal cell carcinoma of the skin characterized by the presence of lobules of basaloid cells which are separated by large distances and represent multifocal discrete tumors.
A variant of basal cell carcinoma presenting as a pale, indurated plaque, usually in the upper trunk or face. Morphologically, it is characterized by the presence of strands, cords, and columns of basaloid cells infiltrating the dermis. Perineural invasion may be present and the basaloid cell infiltrate may extend into deeper tissues.
A skin appendage hamartoma with follicular differentiation. It usually occurs in the head and neck region, particularly the face. It presents as a solitary dome-shaped small lesion. The clinical course is benign.
A benign neoplasm arising from the outer hair sheath and infundibulum. It occurs in the head and neck, usually on the face. It usually presents as an exophytic wart-like lesion or a dome-shaped lesion with smooth surface. Multiple facial lesions are usually associated with Cowden disease.
A benign papillary neoplasm composed of transitional cells which show preservation of the nuclear polarity.
A lesion in which the surface epithelium of the bladder or the renal pelvis and ureter contains transitional cells which display malignant cytologic characteristics. There is no evidence of stromal invasion.
A benign neoplasm that arises from the ciliated respiratory mucosa that lines the nasal cavity and paranasal sinuses. It is classified as inverted papilloma, oncocytic papilloma, and exophytic papilloma. Clinical manifestations include nasal obstruction, epistaxis, and anosmia.
A benign papillary neoplasm composed of transitional cells and characterized by an endophytic growth pattern.
A squamous cell carcinoma of the sinonasal tract characterized by a plexiform or ribbon-like growth pattern, cytological atypia, and lack of histological evidence of keratinization.
A poorly differentiated transitional cell carcinoma characterized by the presence of malignant cells with spindle cell morphologic features.
An anal carcinoma arising from the transitional zone of the anal canal.
A non-invasive or invasive transitional cell carcinoma characterized by a papillary growth pattern. It may occur in the bladder or the renal pelvis.
A lesion in which the normally situated glands are partially or completely replaced by atypical cells with malignant characteristics.
An adenocarcinoma which has spread from its original site of growth to another anatomic site.
An adenocarcinoma which has spread within the mucosa without further invasion of the underlying tissues.
An adenocarcinoma arising from epithelium which has undergone intestinal metaplasia. Representative examples include gastric, gallbladder, and ampulla of Vater intestinal type adenocarcinomas.
An adenocarcinoma characterized by the presence of a diffuse cellular infiltrate which is composed of poorly cohesive cells with minimal or no glandular formations. Representative example is the gastric diffuse adenocarcinoma.
An insulin-producing neuroendocrine tumor arising from the beta cells of the pancreas. Patients exhibit symptoms related to hypoglycemia due to inappropriate secretion of insulin. It displays vascular invasion and metastasizes to other anatomic sites.
A glucagon-producing neuroendocrine tumor arising from the alpha cells of the pancreas. It may be associated with necrolytic erythema migrans, diarrhea, diabetes, glossitis, weight loss, malabsorption, and anemia. It displays vascular invasion and metastasizes to other anatomic sites.
A gastrin-producing neuroendocrine tumor. It is characterized by inappropriate secretion of gastrin and associated with Zollinger Ellison syndrome. It displays vascular invasion and metastasizes to other anatomic sites.
An epithelial, usually multiloculated neoplasm arising from the intrahepatic or extrahepatic bile ducts. It occurs predominantly in females. Signs and symptoms include abdominal mass, abdominal pain, and jaundice. Morphologically, the cystic spaces are lined by columnar epithelium and contain mucinous or serous fluid.
A mucinous cystic neoplasm that arises from the intrahepatic or extrahepatic bile ducts and it is associated with an invasive carcinomatous component.
A distinctive type of liver cell carcinoma that arises in non-cirrhotic livers and is seen predominantly in young patients. The tumor cells are polygonal and deeply eosinophilic, and are embedded in a fibrous stroma. The prognosis is similar to classical hepatocellular carcinoma that arises in non-cirrhotic livers, and better than hepatocellular carcinoma that arises in cirrhotic livers.
A non-invasive adenocarcinoma arising from the neoplastic glandular cells in an adenomatous polyp.
A usually polypoid neoplasm arising from the glandular epithelium. It is characterized by a tubular architectural pattern. The neoplastic glandular cells have dysplastic features. Representative examples include the tubular adenomas of the colon and rectum.
Adenocarcinomas developing in colorectal adenomas in patients with a history of adenomatous polyposis coli. The mean age of development of adenocarcinoma is about 40 years.
A condition in which multiple adenomas develop in the gastrointestinal tract.
Adenocarcinomas developing in gastrointestinal tract adenomas in patients with multiple adenomatous polyps.
A carcinoma morphologically characterized by the presence of solid sheets of malignant epithelial cells in tissues.
An undifferentiated malignant epithelial neoplasm which tends to infiltrate the surrounding tissues and spread to other anatomic sites.
A well differentiated, low grade tumor with neuroendocrine differentiation that arises from the appendix. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A malignant epithelial neoplasm composed of a mixture of neuroendocrine cells with morphologic and immunohistochemical characteristics of carcinoid tumor and malignant glandular cells.
A benign, well circumscribed lung neoplasm morphologically characterized by the presence of cystic spaces resembling alveoli, lined by a simple cuboidal epithelium. The cystic spaces are surrounded by a spindle cell stroma which may show myxoid changes. It is a solitary, usually peripheral lung lesion. Patients are usually asymptomatic and its discovery is an incidental finding during chest X-ray examination. Surgical excision is curative.
A non-invasive adenocarcinoma arising from a villous adenoma.
A non-invasive or invasive adenocarcinoma arising from a villous adenoma.
An adenocarcinoma characterized by the presence of a villous architectural pattern. It may arise from a villous adenoma.
An epithelial neoplasm morphologically characterized by the presence of a villous and a tubular architectural pattern. Most often it occurs in the large intestine, small intestine, and the stomach in which the neoplastic epithelial cells show dysplastic features.
A non-invasive adenocarcinoma arising from a tubulovillous adenoma.
A non-invasive or invasive adenocarcinoma arising from a tubulovillous adenoma.
A malignant epithelial neoplasm of the anterior pituitary gland in which the neoplastic cells stain positive with acidic dyes.
An epithelial neoplasm of the anterior pituitary gland in which the neoplastic cells stain positive with acidic and basic dyes.
A malignant epithelial neoplasm of the anterior pituitary gland in which the neoplastic cells stain positive with acidic and basic dyes.
A malignant epithelial neoplasm of the anterior pituitary gland in which the neoplastic cells stain positive with basic dyes.
A benign neoplasm composed of glands containing epithelial clear cells.
A benign neoplasm characterized by the presence of glandular structures which contain clear cells and a fibrotic stroma.
A carcinoma characterized by the presence of malignant epithelial cells with clear cytoplasm which contains neutral lipids. A representative example is the lipid-rich breast carcinoma.
A carcinoma characterized by the presence of malignant epithelial cells with abundant clear cytoplasm which contains glycogen. A representative example is the glycogen-rich, clear cell breast carcinoma.
A parathyroid gland adenoma composed predominantly of neoplastic chief cells. These cells have either slightly eosinophilic or vacuolated cytoplasm, and round nuclei.
A rare parathyroid gland adenoma composed of neoplastic cells with abundant cytoplasm. The cytoplasm of the neoplastic cells is usually not entirely clear, and is often variably vacuolated, foamy, and granular.
An adenocarcinoma characterized by the presence of malignant epithelial cells with clear, often vacuolated or foamy cytoplasm.
An adenoma characterized by the presence of a mixed epithelial cell population.
An adenocarcinoma characterized by the presence of a mixed malignant glandular cell population.
An adenoma in which the neoplastic epithelial cells are admixed with adipose tissue cells.
A thyroid gland adenoma composed of microfollicular structures.
A thyroid gland adenoma composed of large size follicles.
A benign, well circumscribed neoplasm arising from the cortex of the kidney. It secrets renin and the patients usually present with severe hypertension and marked hypokalemia. Morphologically, it is characterized by the presence of sheets of polygonal or spindle-shaped neoplastic cells forming a hemangiopericytic pattern.
An adenoma of the adrenal cortex composed of neoplastic compact cells with eosinophilic cytoplasm.
A usually functioning adenoma of the adrenal cortex. Grossly, it has a dark brown appearance and is characterized by the presence of neoplastic cells containing abundant intracytoplasmic lipofuscin. It may be associated with Cushing's syndrome.
An adenoma of the adrenal cortex composed of neoplastic clear cells containing intracytoplasmic lipid droplets.
An adenoma of the adrenal cortex composed of neoplastic cells with cytologic features of glomerulosa cells.
An adenoma of the adrenal cortex composed of a mixed neoplastic cellular population, including varying numbers of neoplastic clear and compact cells.
An epithelial neoplasm that arises from the ovary characterized by the presence of glandular or cystic spaces which contain atypical glandular epithelial cells resembling endometrial cells. The surrounding ovarian stroma is often fibrotic. There is no evidence of stromal invasion.
A benign epithelial neoplasm arising from the sebaceous or sweat glands. Representative examples include sebaceous adenoma, tubular apocrine adenoma, and hidradenoma.
A carcinoma with apocrine and less often eccrine differentiation, arising from the sweat glands. It usually presents as a solitary slow growing nodule in the dermis or subcutaneous tissues. It is characterized by a nodular growth pattern and it is often associated with necrotic changes.
A benign dermal adnexal neoplasm with apocrine differentiation. It usually occurs in the scalp and has a female predilection. It presents as an asymptomatic solitary nodule. It is characterized by a lobular architecture. The lobules are composed by tubular structures lined by epithelial cells. There is no cytologic atypia or mitotic figures present.
A benign epithelial neoplasm with eccrine or apocrine differentiation, arising from the sweat glands. It usually presents as a solitary, well circumscribed, firm nodule in the face and upper trunk. It is characterized by the presence of basaloid cells forming nodules in the dermis. Cases of carcinoma arising from long standing spiradenomas have been reported.
A benign neoplasm arising from the sweat glands. It presents as a slow growing cystic nodular lesion most often in the skin of the vulva and the perianal region. It is characterized by the presence of cystic and large papillary structures. The papillary structures contain connective tissue and are covered by two layers of epithelium. Complete excision is curative.
A benign neoplasm arising from the sweat glands. It is characterized by the presence of eccrine ducts in the dermis containing intraluminal papillary projections.
A tumor (abnormal growth of tissue) of the ceruminal gland.
An infiltrating adenocarcinoma derived from ceruminous glands in the external auditory canal.
A serous cystic glandular epithelial neoplasm of low malignant potential. It is characterized by the presence of atypical or malignant glandular epithelial cells with an absence of stromal invasion.
A serous or mucinous cystic glandular epithelial neoplasm of low malignant potential. It is characterized by the presence of atypical or malignant glandular epithelial cells forming papillary structures with an absence of stromal invasion.
A benign, malignant, or borderline neoplasm characterized by the presence of papillary mucinous, serous, or clear cell structures and cystic structures.
A serous benign or low malignant potential cystic epithelial neoplasm characterized by the presence of glandular epithelial cells forming papillary structures.
A malignant cystic serous epithelial neoplasm characterized by the presence of malignant glandular epithelial cells forming papillary structures. Stromal invasion is present.
A non-invasive papillary serous epithelial neoplasm usually arising from the ovary.
An invasive serous adenocarcinoma arising from the ovary. Cases with identical morphology have been described arising in the peritoneum, almost exclusively in women. Morphologically, it may be a well, moderately, or poorly differentiated neoplasm. It is characterized by a papillary growth pattern often associated with the presence of psammoma bodies.
A low malignant potential cystic serous epithelial neoplasm arising from the ovary. Cases with identical morphology have been described arising from the peritoneum as well. It is characterized by an atypical epithelial proliferation and a papillary growth pattern. There is no evidence of destructive stromal invasion.
A usually benign and less often low malignant potential cystic epithelial neoplasm composed of cells which contain intracytoplasmic mucin. It is characterized by the presence of papillary structures.
An invasive adenocarcinoma characterized by cystic changes, papillary growth pattern, and the presence of malignant glandular cells which contain intracytoplasmic mucin.
A low malignant potential cystic epithelial neoplasm usually arising from the ovary. It is composed of glandular cells with intracytoplasmic mucin. It is characterized by an atypical epithelial proliferation and a papillary growth pattern. There is no evidence of destructive stromal invasion.
An invasive adenocarcinoma composed of malignant glandular cells which produce mucin.
A high grade carcinoma characterized by the presence of comedo-type of tumor cell necrosis in which the necrotic areas are surrounded by a solid proliferation of malignant pleomorphic cells.
A rare, low grade invasive adenocarcinoma of the breast characterized by the presence of cells that secrete milk-like material. Morphologically, it usually appears as a circumscribed lesion, composed of cystic spaces, tubular structures, and solid areas.
A non-invasive breast adenocarcinoma located in a distended duct. It is characterized by the presence of papillary structures with fibrovascular stalks. In the absence of ductal carcinoma in situ or invasive carcinoma in adjacent tissues, the prognosis is usually favorable.
A breast adenocarcinoma characterized by the presence of an intraductal papillary carcinomatous component and an invasive carcinomatous component.
A papillary epithelial neoplasm arising in a cystically dilated breast duct.
An intraductal breast carcinoma characterized by a papillary growth within a large cystic duct. There is no evidence of invasion of the breast parenchyma.
A neoplastic process characterized by the presence of multiple intraductal papillomas.
A benign epithelial neoplasm arising from the nipple. Signs and symptoms include serous or sanguineous nipple discharge and nipple erosion. It is characterized by the presence of aggregates of small tubules replacing the nipple stroma. The tubules are lined by epithelial and myoepithelial cells.
A medullary thyroid gland carcinoma characterized by the presence of amyloid stroma. The majority of medullary carcinomas of the thyroid gland are associated with amyloid deposits. The latter are highlighted with Congo red staining method.
The co-existence of ductal and lobular carcinoma in situ in the breast, without evidence of stromal invasion.
A breast carcinoma characterized by the presence of a ductal carcinoma in situ component and an in situ or invasive lobular carcinomatous component.
A benign glandular epithelial neoplasm consisting of secretory cells forming acinar patterns.
A benign or malignant glandular epithelial neoplasm consisting of secretory cells forming acinar patterns. It includes the acinar cell adenoma and acinar cell carcinoma.
A malignant neoplasm which occurs mostly in the major salivary glands (most frequently in the parotid gland), but also in the minor salivary glands of the oral mucosa and the tracheobronchial tree. It is characterized by the presence of ductal structures which are lined by an inner layer of cuboidal epithelial-type cells and an outer layer of myoepithelial cells with clear or eosinophilic cytoplasm.
An invasive adenocarcinoma characterized by the presence of focal or extensive transformation of malignant glandular cells to squamous epithelial cells.
An invasive adenocarcinoma characterized by focal or extensive cartilage and/or bone formation.
An invasive adenocarcinoma characterized by focal or extensive transformation of the malignant glandular cells to spindle-shaped cells.
An invasive adenocarcinoma characterized by focal or extensive transformation of the malignant glandular cells to cells with abundant, usually granular eosinophilic cytoplasm.
A thecoma of the ovary which may metastasize to another anatomic site. It is usually characterized by nuclear atypia and mitotic activity. Malignant thecomas are rare.
A variant of ovarian thecoma characterized by the presence of lutein cells. It is associated with a lower frequency of estrogenic manifestations compared to typical thecomas. In a minority of cases androgenic manifestations are present.
A granulosa cell tumor which has an aggressive clinical course and metastasizes to other anatomic sites.
A general term used to describe sex cord-stromal tumors characterized by the presence of granulosa cells in a thecomatous/fibrothecomatous background.
A granulosa cell tumor occurring in the ovary and testis. In females it occurs predominantly in the first three decades of life and presents unilaterally as stage I disease in the vast majority of cases. It is characterized by the presence of granulosa cells forming macrofollicular structures. The majority of cases have a good prognosis. In males it represents the most frequent congenital testicular neoplasm and the vast majority of cases occur in the perinatal period. It presents as a scrotal or abdominal mass and it more often affects the left testis. Approximately 20% of the patients have ambiguous external genitalia. It is characterized by the presence of cystic spaces lined by granulosa cells and cells resembling theca cells. Metastases have not been reported.
A Sertoli-Leydig tumor of the ovary characterized by the presence of Sertoli cells in tubules without evidence of significant nuclear atypia or mitotic activity. Primitive gonadal stromal cells are not present. It usually follows a benign clinical course.
A Sertoli cell tumor of the testis or the ovary which metastasizes to another anatomic site.
A Leydig cell tumor which does not recur or metastasize. Morphologically, there is no evidence of cellular atypia, increased mitotic activity, necrosis, or vascular invasion.
A Leydig cell tumor characterized by large tumor size, the presence of cytologic atypia, increased mitotic activity, necrosis, and vascular invasion. Approximately 10% of the testicular Leydig cell tumors show malignant characteristics and metastasize. Leydig cell tumors of the ovary follow a benign clinical course.
An ovarian tumor in which the vast majority of the cells (more than 90% of the tumor cells) resemble steroid hormone-secreting cells. It usually presents with androgenic manifestations. Approximately one-third of the cases follow a malignant clinical course.
A benign or malignant paraganglioma arising from the chromaffin cells of the paraganglia that are located along the sympathetic nerves. It includes extra-adrenal paragangliomas and paragangliomas that arise from the adrenal medulla. The latter are commonly referred to as pheochromocytomas. Representative examples of extra-adrenal sympathetic paragangliomas include the bladder, and superior and inferior paraaortic paragangliomas. Clinical signs are related to the secretion of catecholamines resulting in hypertension.
A benign or malignant, usually non-functioning, extra-adrenal paraganglioma that arises from paraganglia located along the parasympathetic nerves. Representative examples include aorticopulmonary, carotid body, jugulotympanic, and mediastinal paragangliomas.
A benign or malignant extra-adrenal parasympathetic paraganglioma that arises from paraganglia adjacent to the base of the heart and great vessels.
An extra-adrenal paraganglioma that metastasizes to regional or distant anatomic sites. Common sites of metastasis include the lymph nodes, lungs, bones, and liver.
A pheochromocytoma that metastasizes to other anatomic sites. Common sites of metastasis include lymph nodes, bones, liver, and lung. Morphologic features associated with malignant pheochromocytomas include: atypical mitotic figures, capsular and vascular invasion, tumor cell necrosis, and high mitotic activity.
A morphologic variant of the glomus tumor characterized by the presence of dilated veins, surrounded by small clusters of glomus cells. Glomangiomas are most often present in patients with multiple lesions.
A morphologic variant of the glomus tumor with architectural features similar to solid glomus tumor. It is characterized by the presence of elongated glomus cells which resemble mature smooth muscle.
A type of melanoma that starts as a raised area that is usually dark blackish-blue or bluish-red but may not have any color.
An uncommon variant of melanocytic nevus. It presents as a small pigmented skin lesion. It is characterized by the presence of large melanocytes with clear, foamy or finely vacuolated cytoplasm. It may recur if it is not completely excised.
A rare variant of melanoma with a vertical growth phase. It presents as a nodular or polypoid skin lesion. It is characterized by the presence of nodules which contain large melanoma cells with clear, foamy or finely vacuolated cytoplasm. The prognosis is similar to that of other melanomas matched for depth of invasion.
A skin lesion characterized by the disappearance of the melanoma cells from the primary melanoma site. The disappearance of the malignant cells is associated with fibroplasia of the papillary dermis. According to some authors, complete regression of the primary melanoma may occur in 4-8% of patients.
An intradermal nevus characterized by the presence of nests of atrophic nevus cells which are hyalinized and resemble nerve bundles.
A benign melanocytic proliferation without metastatic potential.
A benign nevus characterized by the absence of melanin pigment in the melanocytes.
A nevus characterized by the presence of an intraepidermal proliferation of nevus cells. The nevus cells form multiple nests in the dermal-epidermal junction. It presents as a small, slightly raised, pigmented skin lesion.
A melanoma arising from a melanocytic nevus which involves the dermal-epidermal junction of the skin.
A melanoma of the skin. It is characterized by the presence of melanoma cells in the dermal-epidermal junction only, without infiltration of the papillary or reticular dermis.
A type of melanoma that is flat and irregular in shape and color, with different shades of black and brown.
A melanoma characterized by the presence of malignant large epithelioid melanocytes and malignant spindle-shaped melanocytes.
A melanoma characterized by the presence of malignant large epithelioid melanocytes.
A melanoma characterized by the presence of malignant spindle-shaped melanocytes.
A melanoma characterized by the presence of malignant spindle-shaped melanocytes with slender nuclei and no visible nucleoli. Representative example is the type A spindle cell uveal melanoma.
A melanoma characterized by the presence of malignant spindle-shaped melanocytes with larger nuclei and distinct nucleoli. Representative example is the type B spindle cell uveal melanoma.
A rare melanoma which develops in a pre-existing blue nevus. It occurs more frequently on the scalp, face, orbit, back, buttocks, extremities, hands, and feet.
A blue nevus characterized by a multinodular cellular infiltrate with a dumb-bell architecture occupying the reticular dermis. The cellular infiltrate often extends into the subcutaneous tissue. The cellular infiltrate is composed of spindle-shaped melanocytes with pale cytoplasm alternating with bundles of pigmented spindle-shaped melanocytes. In occasional cases an increased mitotic activity, focal necrosis, and nuclear pleomorphism may be seen. Such cases with atypical features may have an uncertain malignant potential.
A non-metastasizing neoplasm that arises from the soft tissue.
The occurrence of several sarcomas in different anatomic locations.
A morphologic variant of dermatofibrosarcoma protuberans characterized by the presence of extensive myxoid stroma formation and a storiform growth pattern.
A benign fibrous neoplasm arising from the periosteal connective tissue that surrounds a bone.
A malignant fibroblastic tumor arising from the periosteal connective tissue that surrounds a bone.
A benign fibrous tumor arising from the fascial connective tissue.
A malignant fibroblastic neoplasm arising from the fascial connective tissue.
A fibrosarcoma that occurs in infants. It shares identical morphologic features with adult fibrosarcoma but carries the t(12;15)(p13;q25) translocation that results in ETV6-NTRK3 gene fusion. It usually affects the superficial and deep soft tissues of the extremities. The prognosis is generally much more favorable than for adult fibrosarcoma, and it rarely metastasizes.
A benign, slow-growing tumor arising from the soft tissues usually in the mid-thoracic region of the elderly. It is characterized by the presence of paucicellular collagenous tissue, adipocytes and a predominance of large coarse elastic fibers arranged in globules.
An undifferentiated soft tissue sarcoma characterized by the presence of a pleomorphic malignant cellular infiltrate. It is also known as malignant fibrous histiocytoma.
A morphologic variant of dermatofibrosarcoma protuberans characterized by the presence of melanin-pigmented dendritic cells.
A benign well-circumscribed tumor composed of mature adipocytes, characterized by areas of abundant fibrous tissue.
A morphologic variant of well differentiated liposarcoma occurring most often in the retroperitoneum and paratesticular area. It is characterized by the presence of bizarre hyperchromatic stromal cells and rare multivacuolated lipoblasts within a fibrous stroma.
A benign well-circumscribed tumor composed of mature adipocytes, characterized by areas of abundant fibrous tissue and extensive myxoid change.
A poorly differentiated liposarcoma, characterized by the presence of solid sheets of primitive round mesenchymal cells and the absence of myxoid stroma.
A malignant neoplasm characterized by the presence of a combination of liposarcomatous morphologic subtypes: myxoid/round cell and well differentiated/dedifferentiated liposarcoma or myxoid/round cell and pleomorphic liposarcoma.
A benign tumor, composed of lobules of mature adipocytes, that penetrates the surrounding tissue from which it arises. There is usually a higher local recurrence rate when compared with non-infiltrating lipomas.
A benign circumscribed tumor composed of spindled cells, adipocytes, and collagen bundles. There is no evidence of nuclear hyperchromasia or mitotic activity.
A benign disorder characterized by the presence of multiple lipoblastomas.
A morphologic variant of classic leiomyoma characterized by a dense cellular infiltrate composed of spindle or round cells with scant cytoplasm and a less obvious interlacing fascicle pattern.
A morphologic variant of leiomyoma characterized by the presence of pleomorphic muscle cells with bizarre hyperchromatic nuclei and eosinophilic cytoplasm.
A malignant smooth muscle neoplasm characterized by the presence of atypical spindle cells and formation of vascular channels.
An aggressive malignant mesenchymal neoplasm with skeletal muscle differentiation, occurring in adults and rarely in children. The tumor is characterized by the presence of bizarre round, spindle, and polygonal cells. Clinical presentation includes a rapidly enlarging painful mass usually of the lower extremities.
A rare benign mesenchymal neoplasm arising from skeletal muscle. It is characterized by the presence of immature spindle and polygonal cells within a scant myxoid stroma. It usually develops in the head and neck region of young children.
A non-infiltrating, benign mesenchymal neoplasm arising from the uterine corpus. It is characterized by the presence of neoplastic cells that resemble the cells of the proliferative phase of endometrial stroma and numerous thin-walled small vessels. It usually presents with abnormal uterine bleeding and menorrhagia.
An infiltrating mesenchymal tumor arising from the uterine corpus, cervix, vagina, and the ovary. It is characterized by the presence of oval to spindle-shape cells that resemble the cells of the endometrial stroma, without evidence of significant atypia and pleomorphism. Numerous small vessels are also present. It is usually characterized by indolent growth and late recurrences.
A rare pediatric sarcoma affecting the kidney. It is characterized by the presence of epithelioid or spindle cells forming cords or nests, separated by fibrovascular septa. It is associated with internal tandem duplications in the BCOR gene. It metastasizes to lung, bone, brain and soft tissue.
A rare malignant epithelial neoplasm arising from the pancreas. The vast majority of cases occur during childhood. It is characterized by acinar differentiation, the formation of squamoid corpuscles, and the formation of stromal bands. Patients may present with an abdominal mass. Symptoms include pain, weight loss, and diarrhea. It may metastasize to lymph nodes, liver, and distant anatomic sites. Children who do not have metastatic disease at the time of diagnosis usually have a favorable clinical outcome when treated with a combination of surgery and chemotherapy. However, children with metastatic disease at presentation or adult patients usually have a poor prognosis.
A term describing a benign soft tissue tumor which consists of two or more mesenchymal lines of differentiation, excluding a fibroblastic line of differentiation.
A term describing a malignant soft tissue tumor which consists of two or more mesenchymal lines of differentiation, excluding a fibroblastic line of differentiation.
A transitional cell neoplasm of low malignant potential arising from the ovary. It is characterized by the presence of neoplastic transitional cells with atypical or malignant features without evidence of stromal invasion.
A malignant neoplasm that arises from the ovary and is characterized by the presence of an invasive malignant transitional cell component and nests of benign transitional cells in a fibrotic stroma. When the neoplasm is confined to the ovary, the prognosis is good.
A morphologic variant of breast fibroadenoma without clinical significance. It is characterized by distortion and compression of the ducts by proliferating stromal cells.
A morphologic variant of breast fibroadenoma without clinical significance. It is characterized by circumferential proliferation of stromal cells around the ducts. This results in the formation of rounded ductal-epithelial structures.
A benign adenofibroma characterized by the presence of serous secretory cells and minute cystic spaces filled with watery fluid. A representative example is the ovarian serous adenofibroma. Cases with epithelial atypia described in the ovary lacking stromal invasion are designated as borderline serous adenofibromas and have a low grade malignant potential.
A benign adenofibroma characterized by the presence of epithelial cells which contain intracytoplasmic mucin and a fibrotic stroma. A representative example is the ovarian mucinous adenofibroma. Cases with epithelial atypia described in the ovary lacking stromal invasion are designated as borderline mucinous adenofibromas and have a low grade malignant potential.
A benign, circumscribed fibroepithelial neoplasm arising from the breast and rarely the prostate gland. It is characterized by the presence of epithelial structures which are arranged in clefts and by a hypercellular mesenchymal stroma which is organized in leaf-like structures. There is no evidence of cellular atypia or sarcomatous features.
A synovial sarcoma characterized by the presence of a spindle cell component only.
A synovial sarcoma characterized by the presence of an epithelial cell component only. The epithelial cells are arranged in glandular or papillary structures.
A synovial sarcoma characterized by the presence of both an epithelial and a spindle cell component.
A localized neoplasm of probable fibroblastic derivation, that arises from the pleura. It is characterized by the presence of round to spindle-shaped cells, hylanized stroma formation, thin-walled branching blood vessels, and thin bands of collagen.
A diffuse malignant mesothelioma arising from the pleura and less often the peritoneum. It is characterized by the presence of spindle cells. Anaplastic morphologic features and multinucleated malignant cells may also be seen.
A malignant neoplasm arising from mesothelial cells in the pleura. It is characterized by the presence of neoplastic epithelioid cells and sarcomatoid features.
A seminoma of the testis characterized by increased cellular pleomorphism, high mitotic activity, and a non-prominent stromal lymphocytic infiltrate.
A rare variant of seminoma characterized by the presence of three cell types: round cells with eosinophilic cytoplasm, small cells with dark nucleus and a small amount of cytoplasm, and mono-or multinucleated giant cells. The neoplastic cells are not cohesive. There is an edematous stroma present; lymphocytic infiltrates are rarely seen. Most patients are older males.
A teratoma composed of immature, fetal-type tissues.
An immature teratoma characterized by the presence of large ammounts of undifferentiated tissues.
An immature teratoma characterized by the presence of an intermediate amount of undifferentiated tissues.
A teratoma which is characterized by morphologic transformation to malignancy and an aggressive clinical course. The malignant component most often is sarcomatous or carcinomatous.
A malignant germ cell tumor characterized by the presence of at least two different germ cell tumor components. The different germ cell tumor components include choriocarcinoma, embryonal carcinoma, yolk sac tumor, teratoma, and seminoma. It occurs in the ovary, testis, and extragonadal sites including central nervous system and mediastinum.
An ovarian mature teratoma characterized by the presence of aberrant thyroid tissue with morphologic changes identical to thyroid carcinoma. Patients may present with abdominal mass and unusual symptoms due to thyrotoxicosis, or with Meigs syndrome (ascites and pleural effusion).
An ovarian neoplasm characterized by the presence of aberrant thyroid tissue and a carcinoid tumor. A minority of patients develop symptoms of functioning thyroid tissue. The neuroendocrine carcinoid cells infiltrate the aberrant thyroid tissue and progressively replace the follicular lining cells.
A malignant mixed germ cell tumor characterized by the presence of a choriocarcinomatous component admixed with another germ cell component (e.g. embryonal carcinoma, teratoma, or seminoma).
A malignant germ cell tumor which metastasizes widely and produces high levels of human chorionic gonadotropin.
A gestational trophoblastic disorder characterized by the presence of an abnormal fetus and two populations of chorionic villi: one population which is unremarkable and a second one which shows hydropic changes.
A benign epithelial neoplasm of the female reproductive system arising from mesonephric remnants.
An epithelial neoplasm of the female reproductive system arising from mesonephric remnants.
A benign vascular lesion characterized by the presence of a complex network of communicating arterial and venous vascular structures.
A benign vascular proliferation characterized by the presence of prominent endothelial cells and the formation of vascular channels.
A skin hemangioma characterized by the presence of epidermal hyperplasia.
A hemangiopericytoma without malignant morphologic or clinical characteristics.
An uncommon malignant neoplasm arising from pericytes. Distinction between benign and malignant hemangiopericytoma may be difficult or even impossible on morphologic grounds alone.
A hemorrhagic lymphatic lesion characterized by the presence of dilated lymphatic spaces, extravasation of red blood cells, hemosiderin deposition, and fibrosis.
An osteoblastoma characterized by the presence of prominent epithelioid osteoblasts and recurrences.
A benign neoplasm of bone surface composed of hyaline cartilage. It arises beneath the periosteum and is characterized by the presence of chondrocytes, a lobulated growth pattern, and calcification.
A chondrosarcoma arising from the surface of bone. It is characterized by a lobulated growth pattern, high mitotic activity, myxoid stroma formation, and necrotic changes. It occurs in adults. Clinical presentation includes pain, and sometimes swelling.
A chondrosarcoma characterized by the presence of myxoid changes.
A malignant tumor that arises from the bone. It is characterized by the presence of an area of high grade sarcoma in an otherwise typical giant cell tumor (primary malignancy in giant cell tumor), or the presence of sarcoma in which the pre-existing giant cell tumor may or may not be apparent (secondary malignancy in giant cell tumor).
A painless, well circumscribed tumor arising in soft tissue, usually of the upper and lower extremities. Morphologically, it is characterized by a multinodular growth pattern. The cellular infiltrate is composed of mononuclear round or oval cells and multinucleated osteoclast-like giant cells, in a rich vascular stroma. It rarely metastasizes.
An undifferentiated pleomorphic sarcoma characterized by the presence of osteoclast-like giant cells and cellular pleomorphism.
A benign, slow growing neoplasm arising from tooth-forming tissues. It occurs in the maxillofacial skeleton or the gingiva. Representative examples include adenomatoid odontogenic tumor, calcifying cystic odontogenic tumor, and squamous odontogenic tumor.
A rare neoplasm arising from tooth-forming tissues. It occurs in the maxillofacial skeleton or the gingiva. Symptoms include swelling, pain, bleeding, mobility of affected teeth, and oral mucosa ulcerations. It may metastasize to lymph nodes and distant anatomic sites early.
A benign, slow growing, and painless hamartomatous tumor occurring in tooth-bearing areas of the jaws. It is one of the most common odontogenic tumors and it usually affects children, adolescents, and young adults. It is characterized by the presence of enamel and dentin and the absence of tooth-like structures. It is treated with local excision. If it is incompletely removed, it may recur.
A benign, slow growing neoplasm arising from tooth-forming tissues. The vast majority of cases are intraosseous and most often grow in the maxilla. It is characterized by the presence of odontogenic epithelium which is embedded in a connective tissue stroma. Local excision is curative and recurrences are very rare.
A carcinoma usually arising from the maxilla and less often the mandible. Symptoms include swelling and paresthesia. It is characterized by the presence of rounded islands of malignant epithelial cells in a fibrous stroma and the benign features of calcifying cystic odontogenic tumor. The clinical course varies from slow growing and locally invasive to rapidly growing and highly aggressive with metastases.
A rare, well differentiated, cytologically benign ameloblastoma which paradoxically metastasizes.
An intraosseous odontogenic neoplasm with good prognosis, arising from the mandible and less frequently from the maxilla. It is characterized by the presence of stellate cells and abundant myxoid stroma formation. Small tumors may be cured with enucleation. Complete excision may be required for larger tumors.
A rare, benign, extraosseous neoplasm arising from tooth-forming tissues. It usually presents as a slow growing exophytic mass in the gingiva. It is characterized by the presence of odontogenic epithelium which is embedded in a fibrous stroma.
A rare neoplasm arising from tooth-forming tissues. It usually arises from the posterior mandible. It is characterized by the presence of an epithelial component and fibromyxoid stroma. It may recur and rarely shows malignant transformation to ameloblastic fibrosarcoma. It is treated with enucleation and curettage.
A locally aggressive malignant neoplasm arising from odontogenic tissue. It occurs in the mandible and less often in the maxilla. It is characterized by the presence of a malignant connective tissue component and a benign epithelial component. The frequency of distal metastases is low.
A slow growing, locally invasive neoplasm arising from tooth-forming tissues. It most often grows intraosseously in the mandible and less frequently in the maxilla. In a minority of cases it grows extraosseously in the gingiva. It is characterized by the presence of a fibrous stroma, epithelial cells with abundant eosinophilic cytoplasm, and amyloid material which is often calcified. Small tumors may be successfully treated with enucleation. Local resection is usually required for larger tumors. Recurrences have been reported in a minority of cases.
A diffuse glial tumor which infiltrates the brain extensively, involving more than two lobes. It is frequently bilateral and often extends to the infratentorial structures, even to the spinal cord. It is probably of astrocytic origin, although GFAP expression may be scant or absent. (Adapted from WHO.)
A rare variant of ependymoma characterized by well formed papillae. Tumor cell processes abutting capillaries are usually GFAP-positive. Differential diagnoses include choroid plexus papilloma, papillary meningioma and metastatic papillary carcinoma. (Adapted from WHO)
A diffusely infiltrating, WHO grade III astrocytoma with focal or dispersed anaplasia, and a marked proliferative potential. It may arise from a low-grade astrocytoma, but it can also be diagnosed at first biopsy, without indication of a less malignant precursor lesion. It has an intrinsic tendency for malignant progression to glioblastoma. (WHO)
A rare variant of diffuse astrocytoma. It is predominantly composed of neoplastic astrocytes showing a small cell body with few, flaccid processes with a low content of glial filaments and scant GFAP expression. This lesion is not well defined and is considered by some authors as an occasional histopathological feature rather than a reproducibly identifiable variant. When occurring in children, this neoplasm may be difficult to separate from pilocytic juvenile astrocytoma. (Adapted from WHO)
A rare variant of diffuse astrocytoma. It is characterized by the presence of a conspicuous, though variable, fraction of gemistocytic neoplastic astrocytes. Gemistocytes are round to oval astrocytes with abundant, glassy, non-fibrillary cytoplasm which appears to displace the dark, angulated nucleus to the periphery of the cell. To make the diagnosis of gemistocytic astrocytoma, gemistocytes should amount to more than approximately 20% of all tumor cells. (Adapted from WHO)
The most frequent histological variant of diffuse astrocytoma. It is predominantly composed of fibrillary neoplastic astrocytes. Nuclear atypia is a diagnostic criterion but mitotic activity, necrosis and microvascular proliferation are absent. The occasional or regional occurrence of gemistocytic neoplastic cells is compatible with the diagnosis of fibrillary astrocytoma. (WHO)
A WHO grade I, relatively circumscribed, slowly growing, often cystic astrocytoma occurring in children and young adults. Histologically it is characterized by a biphasic pattern with compacted bipolar cells associated with Rosenthal fibers and multipolar cells associated with microcysts and eosinophilic bodies/hyaline droplets. (WHO)
A WHO grade ll astrocytic tumor with a relatively favorable prognosis. It is characterized by pleomorphic and lipidized cells expressing GFAP often surrounded by a reticulin network and eosinophilic granular bodies. It presents in the superficial cerebral hemispheres and involves the meninges. It typically affects children and young adults.
A rare glial neoplasm more commonly found in young adults. It is characterized by tumor cells with characteristics suggestive of an astrocytic origin (positive for GFAP), arranged perivascularly. The cells have broad, non-tapering processes radiating towards a central blood vessel. The biologic behavior of astroblastomas is variable, so no WHO grade has been established, yet. (Adapted from WHO.)
A rare histological variant of glioblastoma (WHO grade IV) with a predominance of bizarre, multinucleated giant cells, an occasionally abundant stromal reticulin network, and a high frequency of TP53 mutations. (WHO)
A WHO grade III oligodendroglioma with focal or diffuse malignant morphologic features (prominent nuclear pleomorphism, mitoses, and increased cellularity).
An obsolete term referring to desmoplastic medulloblastoma.
Extensive and diffuse infiltration of tissues by ganglioneuroma.
A primitive neuroectodermal tumor that originates from the cells of the embryonic medullary canal.
A neuroectodermal tumor composed of neoplastic neural elements.
A neurofibroma characterized by the presence of structures which resemble Vater-Pacini corpuscles.
A retinoblastoma with well differentiated features. It often produces Flexner-Wintersteiner rosettes or Homer-Wright rosettes. In some cases the tumor cells form fleurettes.
A retinoblastoma composed of small, undifferentiated cells. It is often associated with necrotic changes.
A rare, benign (olfactory neurocytoma) or malignant (olfactory neuroblastoma) neuroectodermal tumor originating from olfactory receptor cells in the nasal cavity.
A WHO grade I meningioma characterized by the presence of tumor cells that form lobules. The tumor cells are generally uniform. Whorls and psammoma bodies are usually not present.
A WHO grade I meningioma characterized by the presence of spindle cells that form bundles in a collagen matrix.
A WHO grade I meningioma characterized by the presence of psammoma bodies that predominate over the meningeal cells.
A WHO grade I meningioma characterized by the presence of small and medium sized vessels that predominate over the meningioma cells.
An obsolete term referring to hemangiopericytoma of the central nervous system.
A WHO grade I meningioma characterized by the coexistence of meningothelial cells and fibrous architectural patterns.
A rare condition characterized by diffuse spread of sarcoma cells throughout the meninges. The neoplastic cells are derived from meningeal connective tissue. Clinically, this disorder may present as a fulminant pachymeningitis and/or encephalitis.
A rare neurofibroma characterized by the presence of melanin-laden cells and the absence of atypia.
A malignant peripheral nerve sheath tumor which shows rhabdomyosarcomatous differentiation. More than half of the patients have neurofibromatosis type 1. The prognosis is usually poor.
An uncommon granular cell tumor which may metastasize to other anatomic sites. Morphologic characteristics include the presence of spindling neoplastic cells, necrosis, extensive pleomorphism, prominent nucleoli, and increased mitiotic activity.
An antiquated term referring to non-Hodgkin lymphomas with a diffuse architectural pattern.
A nodular sclerosis Hodgkin lymphoma characterized by the presence of lacunar cells, nodular growth, and the absence of fibrosis.
Nodular sclerosis Hodgkin lymphoma in which at least 25% of the tumor nodules contain increased numbers of Reed-Sternberg cells.
A clonal neoplasm of small B-lymphocytes, lymphoplasmacytoid cells, and plasma cells involving the bone marrow, lymph nodes, and the spleen. The majority of patients have a serum IgM paraprotein.
A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).
A clinico-pathological entity reflecting the multiple polyps throughout the gastrointestinal tract created as a result of involvement by a non-Hodgkin lymphoma. Typically, mantle cell lymphomas involving the gastrointestinal tract give rise to multifocal lymphomatous polyposis. Importantly, other histologic subtypes of non-Hodgkin lymphoma can also produce this clinico-pathological entity. (WHO, 2000) -- 2003
Antiquated term describing non-Hodgkin lymphomas that are usually diffuse and are composed of large cells with irregular nuclei, invisible nucleoli and a small amount of cytoplasm. This morphologic category includes both mature B- and mature T-cell lymphomas.--2004
Antiquated term for diffuse non-Hodgkin lymphomas composed of non-cleaved cells. The vast majority of cases are mature B-cell lymphomas (Burkitts or diffuse large B-cell lymphomas).--2004
A variant of peripheral T-cell lymphoma, not otherwise specified. It is characterized by an exclusively perifollicular growth pattern. The neoplastic lymphocytic infiltrate is composed of predominantly small cells with minimal cytologic atypia.
A rare extranodal B-cell non-Hodgkin lymphoma, characterized by the presence of lymphoma cells exclusively in the lumina of small vessels, particularly capillaries. This is an extremely aggressive lymphoma which responds poorly to chemotherapy. (WHO, 2001) -- 2003
An aggressive malignant neoplasm with a poor response to therapy, usually presenting as stage III/IV disease. It is characterized by the presence of neoplastic cells with morphologic and immunophenotypic characteristics similar to those seen in mature histiocytes.
A heterogeneous group of disorders characterized by the abnormal growth and accumulation of mast cells in one or more organ systems. Recent data suggest that most variants of mast cell neoplasms are clonal disorders. (WHO, 2001)
An acute myeloid leukemia characterized by bone marrow fibrosis without preexisting primary myelofibrosis.
An adenoma arising from the renal cortex.
Neoplasms of the endometrial stroma that sometimes involve the MYOMETRIUM. These tumors contain cells that may closely or remotely resemble the normal stromal cells. Endometrial stromal neoplasms are divided into three categories: (1) benign stromal nodules; (2) low-grade stromal sarcoma, or endolymphatic stromal myosis; and (3) malignant endometrial stromal sarcoma (SARCOMA, ENDOMETRIAL STROMAL).
An infiltrating malignant tumor characterized by the presence of atypical cells with myoepithelial differentiation. Representative examples include malignant breast myoepithelioma and salivary gland myoepithelial carcinoma.
A person who inhales or has inhaled combustible products of organic material during their lifetime.
An individual who currently, or recently, smokes cigarettes regularly.
A person who was not smoking at the time of the interview but has smoked at least 100 cigarettes in their life.
An individual who used to drink regularly, but does not drink at the present time.
An astrocytoma, without designation of benign or malignant, that is found in the supratentorial region. The infratentorial location is more common in children.
A hormone producing or non-producing pituitary gland adenoma not associated with a hormonal syndrome.
An adenocarcinoma arising from the colon. It is more frequently seen in populations with a Western type diet and in patients with a history of chronic inflammatory bowel disease. Signs and symptoms include intestinal bleeding, anemia, and change in bowel habits. According to the degree of cellular differentiation, colonic adenocarcinomas are divided into well, moderately, and poorly differentiated. Histologic variants include mucinous adenocarcinoma, signet ring cell carcinoma, medullary carcinoma, serrated adenocarcinoma, cribriform comedo-type adenocarcinoma, and micropapillary adenocarcinoma.
A malignant mesenchymal neoplasm arising from the wall of the uterine corpus (uterine body). The most representative examples are leiomyosarcoma and endometrial stromal sarcoma.
Pan-DR epitope (PADRE) 965.10 is a helper peptide. PADRE peptides have been shown the capacity to deliver help for antibody responses in vivo. They were also found to be able to provide significant helper T-cell activity in vivo. Acts as an adjuvant.
A synthetic agent derived from human papillomavirus (HPV) E7 nuclear protein which is used to produce vaccines against HPV infection and HPV-related neoplasms. HPV E7 oncogenic protein binds the retinoblastoma tumor suppressor protein, pRB, as well as a number of other cellular proteins, and serves as a transcriptional activator. This protein is important in the induction and maintenance of cellular transformation and is co-expressed in the majority of HPV-containing carcinomas. PADRE(R) is a proprietary family of molecules that enhances the immune systems response against an administered immunogen such as the HPV E7 nuclear protein. (NCI04)
An intravenous formulation of tretinoin (vitamin A acid or all-trans retinoic acid) encased in liposomes. Tretinoin is a naturally occurring retinoic acid agent that binds to and activates retinoic acid receptors (RAR), effecting changes in gene expression that lead to cell differentiation, decreased cell proliferation, and inhibition of carcinogenesis. This agent also inhibits telomerase, leading to telomere shortening and eventual apoptosis of certain tumor cell types. Liposome encapsulation extends the half-life of intravenously administered tretinoin.
A monoclonal antibody with potential antineoplastic activity. Specific for both the immunoglobulin G (IgG) receptor CD16 and c-erbB-2, bispecific antibody 2B1 may enhance cellular immune responses against c-erbB-2-positive cells, resulting in increased tumor cell lysis. (NCI04)
A cancer vaccine containing an epitope of glycosphingolipid GD2 conjugated with the immunostimulant keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. The disialoganglioside GD2 is a tumor-associated antigen expressed on the surface of several cancers, including neuroblastoma medulloblastomas, astrocytomas, melanomas, small-cell lung cancer, osteosarcomas, and other soft tissue sarcomas. Vaccination with GD2-KLH vaccine may elicit antibody production against cells expressing GD2 ganglioside, thereby reducing tumor cell growth.
A cancer vaccine consisting of ALVAC, a highly attenuated poxvirus strain derived from the canarypox virus, encoding for the tumor associated antigen (TAA) carcinoembryonic antigen (CEA), with potential antineoplastic activity. Upon administration, ALVAC-CEA vaccine expresses CEA and may stimulate a host immune response against tumor cells expressing CEA. This may result in the inhibition of tumor growth and/or metastasis. CEA is overexpressed in a variety of tumor cell types.
One of a number of recombinant peptides consisting of amino acid residues of the enzyme tyrosinase, a protein frequently expressed by melanoma cells. Vaccination with tyrosinase peptide may stimulate cytotoxic T lymphocyte response against tyrosinase-expressing tumor cells, resulting in decreased tumor growth. (NCI04)
A synthetic long-acting octapeptide analogue of endogenous somatostatin. Octreotide pamoate binds to somatostatin receptors expressed by some neuroendocrine and non-neuroendocrine tumor cells, thereby initiating somatostatin receptor-mediated apoptosis. Other possible antineoplastic activities of this agent include suppression of tumor angiogenesis and tumor growth-promoting insulin-like growth factor 1 (IGF-1). (NCI04)
A pyrimidine analogue and purine nucleoside phosphorylase inhibitor with immunosuppressive and antineoplastic properties. Peldesine inhibits purine nucleoside phosphorylase (PNP) that plays a pivotal role in T-cell proliferation and is responsible for the catalysis of the reversible phosphorolytic cleavage of purine ribonucleosides and 2'-deoxyribonucleosides. Inhibition of PNP results in accumulation of dGTP and the subsequent failure of DNA synthesis. This agent maybe used in T-cell related autoimmune diseases including psoriasis, rheumatoid arthritis and Crohn s disease and T-cell cancers
A pentadentate aromatic metallotexaphyrin with photosensitizing properties. Motexafin lutetium preferentially accumulates in tumor cells due to their increased rates of metabolism and absorbs light, forming an extended high energy conformational state that produces high quantum yields of singlet oxygen, resulting in local cytotoxic effects. (NCI04)
A finding of brain stem glioma in childhood that has not been treated.
The reemergence of brain stem glioma in childhood after a period of remission.
A finding of childhood pineoblastoma that has not been treated.
The reemergence of supratentorial embryonal tumor, not otherwise specified in childhood after a period of remission.
A finding of visual pathway glioma in childhood that has not been treated.
The reemergence of visual pathway glioma in childhood after a period of remission.
A finding of cerebellar astrocytoma in childhood that has not been treated.
Regrowth of benign and malignant childhood cerebellar astrocytomas that have previously been subjected to surgical resection and less frequently other forms of therapy such as radiation or chemotherapy. Recurrence of benign tumors (e.g., (pilocytic astrocytoma) may respond to a second surgical procedure.
The reemergence of cerebral astrocytoma in childhood after a period of remission.
A finding of medulloblastoma in childhood that has not been treated.
The reemergence of childhood medulloblastoma after a period of remission.
An orally-active synthetic hydroxamate with potential antineoplastic activity. Marimastat covalently binds to the zinc(II) ion in the active site of matrix metalloproteinases (MMPs), thereby inhibiting the action of MMPs, inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. This agent may also inhibit tumor necrosis factor-alpha converting enzyme (TACE), an enzyme involved in tumor necrosis factor alpha (TNF-alpha) production that may play a role in some malignancies as well as in the development of arthritis and sepsis. (NCI04)
A modified peptide antigen derived from gp209, with potential immunomodulatory and antineoplastic activities. gp209-2M antigen (IMDQVPFSV) has a methionine substitution of threonine at position 2 of gp209 peptide (ITDQVPFSV), which is the immunogenic epitope of human melanoma tumor glycoprotein gp100. Vaccination with this peptide may evoke a cytotoxic T lymphocyte (CTL) response against tumor cells expression of the gp100 antigen.
A form of gram-negative meningitis that tends to occur in neonates, in association with anatomical abnormalities (which feature communication between the meninges and cutaneous structures) or as OPPORTUNISTIC INFECTIONS in association with IMMUNOLOGIC DEFICIENCY SYNDROMES. In premature neonates the clinical presentation may be limited to ANOREXIA; VOMITING; lethargy; or respiratory distress. Full-term infants may have as additional features FEVER; SEIZURES; and bulging of the anterior fontanelle. (From Menkes, Textbook of Child Neurology, 5th ed, pp398-400)
A paraneoplastic syndrome marked by degeneration of neurons in the LIMBIC SYSTEM. Clinical features include HALLUCINATIONS, loss of EPISODIC MEMORY; ANOSMIA; AGEUSIA; TEMPORAL LOBE EPILEPSY; DEMENTIA; and affective disturbance (depression). Circulating anti-neuronal antibodies (e.g., anti-Hu; anti-Yo; anti-Ri; and anti-Ma2) and small cell lung carcinomas or testicular carcinoma are frequently associated with this syndrome.
A parasitic infection with tapeworms of the genus Taenia affecting the brain. It is manifested with seizures and headaches.
Frontotemporal dementia (FTD) refers to a clinical manifestation of the pathologic finding of frontotemporal lobar degeneration (FTLD). FTD, the most common subtype of FTLD, is a behavioral variant characterized by changes in social and personal conduct with loss of volition, executive dysfunction, loss of abstract thought, and decreased speech output. A second clinical subtype of FTLD is 'semantic dementia,' characterized by specific loss of comprehension of language and impaired facial and object recognition. A third clinical subtype of FTLD is 'primary progressive aphasia' (PPA), characterized by a reduction in speech production, speech errors, and word retrieval difficulties resulting in mutism and an inability to communicate. All subtypes have relative preservation of memory, at least in the early stages. FTLD is often associated with parkinsonism or motor neuron disease (MND) resembling amyotrophic lateral sclerosis (ALS; 105400) (reviews by Tolnay and Probst, 2002 and Mackenzie and Rademakers, 2007). Mackenzie et al. (2009, 2010) provided a classification of FTLD subtypes according to the neuropathologic findings (see PATHOGENESIS below). Clinical Variability of Tauopathies Tauopathies comprise a clinically variable group of neurodegenerative diseases characterized neuropathologically by accumulation of abnormal MAPT-positive inclusions in nerve and/or glial cells. In addition to frontotemporal dementia, semantic dementia, and PPA, different clinical syndromes with overlapping features have been described, leading to confusion in the terminology (Tolnay and Probst, 2002). Other terms used historically include parkinsonism and dementia with pallidopontonigral degeneration (PPND) (Wszolek et al., 1992); disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) (Lynch et al., 1994); frontotemporal dementia with parkinsonism (FLDEM) (Yamaoka et al., 1996); and multiple system tauopathy with presenile dementia (MSTD) (Spillantini et al., 1997). These disorders are characterized by variable degrees of frontal lobe dementia, parkinsonism, motor neuron disease, and amyotrophy. Other neurodegenerative associated with mutations in the MAPT gene include Pick disease (172700) and progressive supranuclear palsy (PSP; 601104), Inherited neurodegenerative tauopathies linked to chromosome 17 and caused by mutation in the MAPT gene have also been collectively termed 'FTDP17' (Lee et al., 2001). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), PSP, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies. Genetic Heterogeneity of Frontotemporal Lobar Degeneration Mutations in several different genes can cause frontotemporal dementia and frontotemporal lobar degeneration, with or without motor neuron disease. See FTLD with TDP43 inclusions (607485), caused by mutation in the GRN gene (138945) on chromosome 17q21; FTLD mapping to chromosome 3 (600795), caused by mutation in the CHMP2B gene (609512); inclusion body myopathy with Paget disease and FTD (IBMPFD; 167320), caused by mutation in the VCP gene (601023) on chromosome 9p13; ALS6 (608030), caused by mutation in the FUS gene (137070) on 16p11; ALS10 (612069), caused by mutation in the TARDBP gene (605078) on 1p36; and FTDALS (105550), caused by mutation in the C9ORF72 gene (614260) on 9p. In 1 family with FTD, a mutation was identified in the presenilin-1 gene (PSEN1; 104311) on chromosome 14, which is usually associated with a familial form of early-onset Alzheimer disease (AD3; 607822).
A progressive loss of the ability to remember the meaning of words, faces and objects.
A paroxysmal dystonic movement disorder occurring in association with gastro-esophageal reflux, and, in some cases, hiatal hernia. The prevalence is unknown. Onset usually occurs during infancy or early childhood. The dystonic movements are characterized by abnormal posturing of the head and neck (torticollis) and severe arching of the spine. The dystonic movements are clearly associated with gastro-esophageal reflux but the pathophysiological mechanism is not clearly understood.
A nonspecific term referring both to the pathologic finding of swelling of distal portions of axons in the brain and to disorders which feature this finding. Neuroaxonal dystrophy is seen in various genetic diseases, vitamin deficiencies, and aging. Infantile neuroaxonal dystrophy is an autosomal recessive disease characterized by arrested psychomotor development at 6 months to 2 years of age, ataxia, brain stem dysfunction, and quadriparesis. Juvenile and adult forms also occur. Pathologic findings include brain atrophy and widespread accumulation of axonal spheroids throughout the neuroaxis, peripheral nerves, and dental pulp. (From Davis & Robertson, Textbook of Neuropathology, 2nd ed, p927)
A loss of myelin from nerve fibers in the central nervous system.
A migraine disorder characterized by episodes that occur in the absence of preceding focal neurological symptoms.
Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including familial hemiplegic migraine) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech); FHM must include motor involvement, i.e., hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with FHM1 have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia. Cerebral infarction and death have rarely been associated with hemiplegic migraine.
An episode of migraine that persists for more than 72 hours.
A congenital abnormality characterized by the underdevelopment of the optic nerve.
Microphthalmia, anophthalmia, and coloboma comprise the MAC spectrum of ocular malformations. Microphthalmia refers to a globe with a total axial length that is at least two standard deviations below the mean for age. Anophthalmia refers to complete absence of the globe in the presence of ocular adnexa (eyelids, conjunctiva, and lacrimal apparatus). Coloboma refers to the ocular malformations that result from failure of closure of the optic fissure. Chorioretinal coloboma refers to coloboma of the retina and choroid. Iris coloboma causes the iris to appear keyhole-shaped. Microphthalmia, anophthalmia, and coloboma may be unilateral or bilateral; when bilateral they may occur in any combination.
Optic atrophy type 1 (OPA1, or Kjer type optic atrophy) is characterized by bilateral and symmetric optic nerve pallor associated with insidious decrease in visual acuity (usually between ages 4 and 6 years), visual field defects, and color vision defects. Visual impairment is usually moderate (6/10 to 2/10), but ranges from mild or even insignificant to severe (legal blindness with acuity <1/20). The visual field defect is typically centrocecal, central, or paracentral; it is often large in those with severe disease. The color vision defect is often described as acquired blue-yellow loss (tritanopia). Other findings can include auditory neuropathy resulting in sensorineural hearing loss that ranges from severe and congenital to subclinical (i.e., identified by specific audiologic testing only). Visual evoked potentials are typically absent or delayed; pattern electroretinogram shows an abnormal N95:P50 ratio. Tritanopia is the classic feature of color vision defect, but more diffuse nonspecific dyschromatopsia is not uncommon. Ophthalmoscopic examination discloses temporal or diffuse pallor of the optic discs, sometimes associated with optic disc excavation. The neuroretinal rim shows some pallor in most cases, sometimes associated with a temporal pigmentary gray crescent.
Formation or presence of a blood clot (THROMBUS) in the SUPERIOR SAGITTAL SINUS or the inferior sagittal sinus. Sagittal sinus thrombosis can result from infections, hematological disorders, CRANIOCEREBRAL TRAUMA; and NEUROSURGICAL PROCEDURES. Clinical features are primarily related to the increased intracranial pressure causing HEADACHE; NAUSEA; and VOMITING. Severe cases can evolve to SEIZURES or COMA.
A separation (dissection) of the layers of the carotid artery wall.
Splitting of the vessel wall in the VERTEBRAL ARTERY. Interstitial hemorrhage into the media of the vessel wall can lead to occlusion of the vertebral artery, aneurysm formation, or THROMBOEMBOLISM. Vertebral artery dissection is often associated with TRAUMA and injuries to the head-neck region but can occur spontaneously.
A condition characterized by sudden, temporary, usually short-lived memory loss, not associated with a neurologic disorder. Affected individuals lose memory function for recent events and have a decreased ability to retain new information. It is usually a solitary event.
A type of cerebral palsy defined by increased tone and pathological reflexes resulting in an abnormal pattern of movement and posture.
A cyst occurring within the choroid plexus within a cerebral ventricle.
Physical and psychological dependence on hallucinogenics, which is associated with a pattern of continuous use.
Physical and psychological dependence on hallucinogenics, which is associated with a pattern of episodic use.
Physical and psychological dependence on the drug cannabis, which is associated with a pattern of continuous use.
Physical and psychological dependence on the drug cannabis, which is associated with a pattern of episodic use.
Physical or psychological dependence on the drug cocaine which is associated with a pattern of continuous use.
Physical and psychological dependence on the drug cocaine, which is associated with a pattern of episodic use.
Strong physiological and emotional dependence on OPIUM.
A state of abnormally elevated or irritable mood, arousal, and or energy levels.
A respiratory malfunction for which mental factors play a causative role.
A non-metastasizing neoplasm that arises from the upper or lower eyelid.
A capillary hemangioma arising from the eyelid.
A melanoma that arises from the upper or lower eyelid.
An autoimmune disorder of the EYE, occurring in patients with Graves disease. Subtypes include congestive (inflammation of the orbital connective tissue), myopathic (swelling and dysfunction of the extraocular muscles), and mixed congestive-myopathic ophthalmopathy.
The presence of air or gas in the subcutaneous tissue of the orbit of the eye.
Acute conjunctival inflammation in the newborn, usually caused by maternal gonococcal infection. The causative agent is NEISSERIA GONORRHOEAE. The baby's eyes are contaminated during passage through the birth canal.
Partial fusion of the upper and lower eyelid margins by single or multiple bands of tissue. [pmid:18125427]
A localized defect in the anterior eye wall with protrusion of uveal tissue due to alterations in scleral thickness and structure.
Gelatinous drop-like corneal dystrophy is an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness. Clinical manifestations, which appear in the first decade of life, include blurred vision, photophobia, and foreign-body sensation. By the third decade, raised, yellowish-gray, gelatinous masses severely impair visual acuity, and lamellar keratoplasty is required for most patients (summary by Tsujikawa et al., 1999).
Meesmann corneal dystrophy is a dominantly inherited disorder characterized by fragility of the anterior corneal epithelium and intraepithelial microcyst formation. Although the disease is generally mild and affected individuals are often asymptomatic, some suffer from recurrent erosions leading to lacrimation, photophobia, and deterioration in visual acuity (summary by Szaflik et al., 2008).
Posterior polymorphous corneal dystrophy (PPCD) is a rare disorder involving metaplasia and overgrowth of corneal endothelial cells (Krafchak et al., 2005). In patients with PPCD, these cells manifest in an epithelial morphology and gene expression pattern, produce an aberrant basement membrane, and, sometimes, spread over the iris and nearby structures in a way that increases the risk for glaucoma. Symptoms can range from very aggressive to asymptomatic and nonprogressive, even within the same family. The age of diagnosis is, most often, in the second or third decade of life. Clinically, PPCD is characterized by vesicles, bands, and polymorphous opacities at the level of the Descemet membrane and corneal endothelium. Peripheral anterior iris adhesions, iris atrophy, pupillary ectropion, and corectopia may also develop. Occasional severe visual disability results from secondary glaucoma or corneal edema. On ultrastructural examination, corneal endothelial cells show fibroblastic and epithelial-like transformation (summary by Liskova et al., 2012). Genetic Heterogeneity of Posterior Polymorphous Corneal Dystrophy Other forms of PPCD include PPCD2 (609140), caused by mutation in the COL8A2 gene (120252) on chromosome 1p34.3; PPCD3 (609141), caused by mutation in the ZEB1 gene (189909) on chromosome 10p; and PPCD4 (618031), caused by mutation in the GRHL2 gene (608576) on chromosome 8q22.
Any anatomic abnormality or physiologic dysfunction of the lens of the eye that is present at the time of birth.
A cataract that affects the capsule of the lens.
One or both of the following: A. Neocascularization B. Vitreous/Preretinal Hemorrhage
A creamy appearance of the retinal blood vessels that occurs when the concentration of lipids in the blood are extremely increased, with pale pink to milky white retinal vessels and altered pale reflexes from choroidal vasculature.
Best vitelliform macular dystrophy is a slowly progressive macular dystrophy with onset generally in childhood and sometimes in later teenage years. Affected individuals initially have normal vision followed by decreased central visual acuity and metamorphopsia. Individuals retain normal peripheral vision and dark adaptation. Age of onset and severity of vision loss show inter- and intrafamilial variability.
Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by Chung and Traboulsi, 2009). Genetic Heterogeneity of Leber Congenital Amaurosis LCA2 (204100) is caused by mutation in the RPE65 gene (RPE65; 180069) on chromosome 1p31. LCA3 (604232) is caused by mutation in the SPATA7 gene (609868) on chromosome 14q31. LCA4 (604393) is caused by mutation in the AIPL1 gene (604392) on chromosome 17p13. LCA5 (604537) is caused by mutation in the LCA5 gene (611408) on chromosome 6q14. LCA6 (613826) is caused by mutation in the RPGRIP1 gene (605446) on chromosome 14q11. LCA7 (613829) is caused by mutation in the CRX gene (602225) on chromosome 19q13. LCA8 (613835) is caused by mutation in the CRB1 gene (604210) on chromosome 1q31. LCA9 (608553) is caused by mutation in the NMNAT1 gene (608700) on chromosome 1p36. LCA10 (611755) is caused by mutation in the CEP290 gene (610142) on chromosome 12q21 and may account for as many as 21% of cases of LCA. LCA11 (613837) is caused by mutation in the IMPDH1 gene (146690) on chromosome 7q32. LCA12 (610612) is caused by mutation in the RD3 gene (180040) on chromosome 1q32. LCA13 (612712) is caused by mutation in the RDH12 gene (608830) on chromosome 14q24. LCA14 (613341) is caused by mutation in the LRAT gene (604863) on chromosome 4q32. LCA15 (613843) is caused by mutation in the TULP1 gene (602280) on chromosome 6p21. LCA16 (614186) is caused by mutation in the KCNJ13 gene (603208) on chromosome 2q37. LCA17 (615360) is caused by mutation in the GDF6 gene (601147) on chromosome 8q22. LCA18 (see 608133) is caused by mutation in the PRPH2 gene (179605) on chromosome 6p21. Perrault et al. (1999) provided a review of Leber congenital amaurosis, with emphasis on genetic heterogeneity. Wiszniewski et al. (2011) analyzed 13 known LCA genes in 60 LCA probands, and identified homozygous or compound heterozygous mutations in 42 (70%). In addition, a third disease-associated mutant allele at a second locus was identified in 7 (12%) of the 60 patients. Wiszniewski et al. (2011) stated that the significance of the third mutated allele was unknown, but suggested that mutational load might be important to penetrance of the LCA phenotype. Because LCA manifests very early in life and results in profound vision loss, patients with mutations in other syndromic or nonsyndromic eye disease genes may receive an initial diagnosis of LCA, prior to development of syndromic features or before more thorough phenotyping can be performed (see, e.g., Senior-Loken syndrome-5, 609254).
Usher syndrome type II is characterized by: Congenital, bilateral sensorineural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies; Intact vestibular responses; and Retinitis pigmentosa (RP). RP is progressive, bilateral, symmetric retinal degeneration that begins with night blindness and constricted visual fields (tunnel vision) and eventually includes decreased central visual acuity; the rate and degree of vision loss vary within and among families.
X-linked congenital stationary night blindness is a disorder of the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing in low light (night blindness). They also have other vision problems, including loss of sharpness (reduced acuity), severe nearsightedness (high myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus). Color vision is typically not affected by this disorder.The vision problems associated with this condition are congenital, which means they are present from birth. They tend to remain stable (stationary) over time.Researchers have identified two major types of X-linked congenital stationary night blindness: the complete form and the incomplete form. The types have very similar signs and symptoms. However, everyone with the complete form has night blindness, while not all people with the incomplete form have night blindness. The types are distinguished by their genetic cause and by the results of a test called an electroretinogram, which measures the function of the retina.
Blue cone (OPN1SW; 613522) monochromatism is a rare X-linked congenital stationary cone dysfunction syndrome characterized by the absence of functional long wavelength-sensitive and medium wavelength-sensitive cones in the retina. Color discrimination is severely impaired from birth, and vision is derived from the remaining preserved blue (S) cones and rod photoreceptors. BCM typically presents with reduced visual acuity, pendular nystagmus, and photophobia. Patients often have myopia (review by Gardner et al., 2009). There is evidence for progression of disease in some BCM families (Nathans et al., 1989; Ayyagari et al., 2000; Michaelides et al., 2005).
Sharply demarcated, congenital hyperpigmentation of thr retinal pigment epithelium.
Quigley (1993) reviewed adult-onset primary open angle glaucoma, which combines a particular abnormal appearance of the optic disc (optic nerve head) with a slowly progressive loss of visual sensitivity. Many patients with glaucoma have intraocular pressures above the normal range, although this cannot be considered part of the definition of the disease, since some patients have normal intraocular pressures. Changes in the optic disc, either inherited or acquired, contribute to the development of the disorder, which leads to visual loss from increasing nerve fiber layer atrophy. Quigley et al. (1994) stated that POAG should be reviewed as a multifactorial disorder. Genetic Heterogeneity of Primary Open Angle Glaucoma Other forms of primary open angle glaucoma include GLC1A (137750), caused by mutation in the MYOC gene (601652) on chromosome 1q24.3-q25.2; GLC1B (606689) on chromosome 2cen-q13; GLC1C (601682) on chromosome 3q21-q24; GLC1D (602429) on chromosome 8q23; GLC1F (603383), caused by mutation in the ASB10 gene on chromosome 7q36; GLC1G (609887), caused by mutation in the WDR36 gene (609669) on chromosome 5q22; GLC1H (611276) on chromosome 2p16-p15; GLC1I (609745) on chromosome 15q11-q13; GLC1J (608695) on chromosome 9q22; GLC1K (608696) on chromosome 20p12; GLC1L (see 137750) on chromosome 3p22-p21; GLC1M (610535) on chromosome 5q22; GLC1N (611274) on chromosome 15q22-q24; GLC1O (613100), caused by mutation in the NTF4 gene (162662) on chromosome 19q13.3; GLC1P (177700), caused by an approximately 300-kb duplication on chromosome 12q24, most likely involving the TBK1 gene (604834). Nail-patella syndrome (NPS; 161200), which is caused by mutation in the LMX1B gene (602575) on chromosome 9q34, has open angle glaucoma as a pleiotropic feature. Other Forms of Glaucoma For a general description and a discussion of genetic heterogeneity of congenital forms of glaucoma, see GLC3A (231300). See 606657 for a discussion of normal tension glaucoma (NTG) or normal pressure glaucoma (NPG), a subtype of POAG.
Convergent squint which follows loss or impairment of vision. [ORCID:0000-0003-0986-4123]
Esotropia in a patient who has previously had exotropia or exophoria; may be constant or intermittent. and usually follows surgical overcorrection. [ORCID:0000-0003-0986-4123]
Exotropia in an individual who has previously had esotropia or esophoria. [ORCID:0000-0003-0986-4123]
An incomitant tendency for an occluded eye to elevate and extort which resolves on uncovering. [ISBN-13:978-0199679980]
A type of incomitant strabismus in which both elevator muscles (i.e., the inferior oblique and superior rectus muscles) of the same eye are weak leading to restricted elevation and hypotropia. [ORCID:0000-0003-0986-4123, PMID:23479532]
An ocular movement abnormality characterised by simultaneous weakness of the inferior rectus muscle and superior oblique muscle of the same eye. [ORCID:0000-0003-0986-4123]
A supranuclear gaze palsy is an inability to look in a vertical direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.
Voluntary nystagmus is a rapid to-and-fro synchronous movement of the eyes that is initiated and maintained by conscious effort. Voluntary nystagmus has a frequency of 10-25 Hz, with an amplitude of up to 6 degrees, and can be maintained for up to 35 seconds. It usually has its first appearance between ages 8 to 15 years. It can be produced in both light and darkness, without fixation, at all eye positions, and even with closed eyes. It is accompanied by oscillopsia with visual blurring (summary by Aschoff et al., 1976).
A term to describe when farsightedness is masked when the accommodative muscles are used to increase the focusing power of the eye. []
A type of refractive error related abnormal curvatures on the anterior or posterior surface of the cornea. [ORCID:0000-0003-0986-4123]
A type of astigmatism related to an irregular shape of the lens. []
Paralysis of the iris and ciliary apparatus.
Repetitive visual hallucinations experienced mostly by elderly with diminished visual acuity or visual field loss, with awareness of the fictional nature of their hallucinations. It is not associated with delusions and other sensory hallucinations.
A benign polypoid growth in the external ear.
complete loss of the ability to hear from both ears since birth, regardless of causation.
The disposition to develop an allergic reaction to a substance derived from dust mites e.g. Der p1, rather than the dust mite organism itself.
A polyp that arises from the frontal sinus mucosa. It is characterized by the presence of edematous tissue infiltrated by inflammatory cells, including eosinophils. Causes include allergic rhinitis, chronic sinusitis, and cystic fibrosis.
A non-neoplastic or neoplastic disorder that affects the nasal cavity. Representative examples include inflammatory disorders, papillomas, and carcinomas.
An epithelium-lined cyst in the nasal cavity.
A benign exophytic squamous cell neoplasm with papillary growth that arises from the nasal vestibule.
A midline anterior-posterior cleft of the epiglottis that involves at least two-thirds of the epiglottic leaf. It is a useful feature for clinical diagnosis because it appears to be very rare in syndromes other than Pallister-Hall-Syndrome and is also rare as an isolated malformation.
Presence of a cyst (sac-like structure) located in the larynx.
It is a bilateral reticular pattern of linear or lineonodular densities that are most pronounced in basilar portions of the lungs on standard chest x-ray. It is the third minor criterion for scleroderma diagnosis.
Pneumonia caused by infections with the genus CHLAMYDIA; and CHLAMYDOPHILA, usually with CHLAMYDOPHILA PNEUMONIAE.
Accumulation of lymph fluid in the pleural cavity as a result of thoracic trauma.
Young syndrome is characterized by chronic sinopulmonary infections, persistent azoospermia, and normal spermatogenesis (Handelsman et al., 1984).
Lymphangiomyomatosis involving the dermis.
Replacement of the lung tissue by connective tissue in a specific area of the lung.
A rare type of pneumoconiosis caused by long standing exposure to barium dust. It is characterized by the formation of fine dense lesions in the lung parenchyma. The lesions do not affect the lung function and disappear without treatment after the exposure to barium dust stops.
Pneumoconiosis caused by the inhalation of mixed mineral dust particles.
Pneumoconiosis caused by exposure to slate dust.
Respiratory failure due to a low level of oxygen in the blood without a high level of carbon dioxide.
An abnormal communication between the trachea and another organ or anatomic site.
Blockage of the lumen of the trachea. Causes include secretions, foreign bodies, and tumors.
A congenital or acquired condition of underdeveloped or degeneration of CARTILAGE in the TRACHEA and the BRONCHI. This results in a floppy non-rigid airway making patency difficult to maintain.
Enlargement of the cardiac ventricular muscle tissue with increase in the width of the wall of the ventricle and loss of elasticity. Ventricular hypertrophy is clinically differentiated into left and right ventricular hypertrophy.
Angina pectoris which has not recently changed in frequency, duration or intensity. Stable angina pectoris is relieved by rest or administration or oral, sublingual or transdermal antianginal medications.
MYOCARDIAL INFARCTION in which the anterior wall of the heart is involved. Anterior wall myocardial infarction is often caused by occlusion of the left anterior descending coronary artery. It can be categorized as anteroseptal or anterolateral wall myocardial infarction.
MYOCARDIAL INFARCTION in which the inferior wall of the heart is involved. It is often caused by occlusion of the right coronary artery.
A history of myocardial infarction in the absence of clinical symptoms and positive electrocardiographic findings.
Endocarditis occurring on parts of a valve prosthesis or a reconstructed heart valve; it can be classified into early and late prosthetic valve endocarditis.
A fixed form of obstruction to blood flow across the left-ventricular outflow tract related to stenosis (narrowing) below the level of the aortic valve.
Familial restrictive cardiomyopathy is a genetic form of heart disease. For the heart to beat normally, the heart (cardiac) muscle must contract and relax in a coordinated way. Oxygen-rich blood from the lungs travels first through the upper chambers of the heart (the atria), and then to the lower chambers of the heart (the ventricles).In people with familial restrictive cardiomyopathy, the heart muscle is stiff and cannot fully relax after each contraction. Impaired muscle relaxation causes blood to back up in the atria and lungs, which reduces the amount of blood in the ventricles.Familial restrictive cardiomyopathy can appear anytime from childhood to adulthood. The first signs and symptoms of this condition in children are failure to gain weight and grow at the expected rate (failure to thrive), extreme tiredness (fatigue), and fainting. Children who are severely affected may also have abnormal swelling or puffiness (edema), increased blood pressure, an enlarged liver, an abnormal buildup of fluid in the abdominal cavity (ascites), and lung congestion. Some children with familial restrictive cardiomyopathy do not have any obvious signs or symptoms, but they may die suddenly due to heart failure. Without treatment, the majority of affected children survive only a few years after they are diagnosed.Adults with familial restrictive cardiomyopathy typically first develop shortness of breath, fatigue, and a reduced ability to exercise. Some individuals have an irregular heart beat (arrhythmia) and may also experience a sensation of fluttering or pounding in the chest (palpitations) and dizziness. Abnormal blood clots are commonly seen in adults with this condition. Without treatment, approximately one-third of adults with familial restrictive cardiomyopathy do not survive more than five years after diagnosis.
Pericarditis that is caused by an infection with a bacterial agent.
A group of cardiac arrhythmias in which the cardiac contractions are not initiated at the SINOATRIAL NODE. They include both atrial and ventricular premature beats, and are also known as extra or ectopic heartbeats. Their frequency is increased in heart diseases.
Accessory pathway-related atrioventricular reentrant tachycardia (AVRT) involves an abnormal electrical conduction of the accessory pathway. The accessory pathway connecting impulses between the atrium and the ventricle can be seen at any site in the AV groove. []
A congenital disorder characterized by an electrocardiographic finding of tachycardia that affects neonates and infants. It results from an increased automaticity in the atrioventricular node and His bundle.
An incessant orthodromic tachycardia with anterograde conduction over the atrioventricular node and by retrograde conduction via an accessory pathway usually located in the posteroseptal region with slow and decremental conduction.
A disorder characterized by an electrocardiographic finding of a complete atrioventricular block that manifests during fetal life or soon after birth. It may be isolated or associated with other congenital heart defects. Isolated congenital complete atrioventricular block may be associated with maternal connective tissue disorders.
Presence of a blood clot in the atria of the heart.
A disease or disorder that is associated with a transplanted heart.
A rare, progressive, autosomal dominant inherited disorder. It is caused by mutation in the BMPR2 gene in most cases. It is characterized by abnormally high blood pressure in the pulmonary artery, caused by obstruction and obliteration of the small pulmonary arteries.
The formation of a thrombus in the renal artery.
Abnormal outpouching or sac-like dilatation in the wall of the inferior mesenteric artery .
A dilatation (balooning or bulging out of the vessel wall) of a carotid artery.
A progressive tear in the tissue lining the aorta, characterized by the passage of blood from the tunica intima into, and partially through, the tunica media.
Acute occurrence of a dissection (tear within the tunica intima and entry of blood into the tunica media) of a coronary artery.
A finding indicating narrowing of a vein in one or multiple areas.
Narrowing of the lumen of the subclavian vein.
Abnormal narrowing of the lumen of the inferior vena cava.
Abnormal narrowing of the lumen of the superior vena cava.
Capillary malformations are a form of vascular malformation that are present from birth, tend to grow with the individual, do not regress spontaneously, and show normal rates of endothelial cell turnover. Capillary malformations are distinct from capillary hemangiomas (602089), which are highly proliferative lesions that appear shortly after birth and show rapid growth, slow involution, and endothelial hypercellularity (Spring and Bentz, 2005; Legiehn and Heran, 2006).
Pulmonary venoocclusive disease-2 is an autosomal recessive subtype of primary pulmonary hypertension (PPH; see 178600). It is characterized histologically by widespread fibrous intimal proliferation of septal veins and preseptal venules, and is frequently associated with pulmonary capillary dilatation and proliferation. The disorder can cause occult alveolar hemorrhage. High-resolution CT imaging of the chest shows patchy centrilobular ground-glass opacities, septal lines, and lymph node enlargement (summary by Eyries et al., 2014). For a discussion of genetic heterogeneity of pulmonary venoocclusive disease, see PVOD1 (265450).
An electrocardiographic finding of the presence of cardiac electrical rhythm without a proper response of the myocardial tissue and mechanical cardiac output.
Narrowing of the lumen of an arteriovenous fistula.
Partial or complete occlusion of the lumen within an arteriovenous fistula by a thrombus.
Failure to capture manifests as a high pacing threshold that results in either intermittent failure to capture at maximal programmed output or excessive battery drain leading to premature battery exhaustion.
Inappropriate pacemaker detection of electrical signals not related to cardiac depolarization of the lead chamber.
Failure of pacemaker to detect appropriate cardiac depolarizations.
A disease characterized by normocytic, normochromic anemia, low hematocrit, reticulocytopenia and selective erythroid hypoplasia. It can occur as a chronic or acute form; the former is predominantly seen in adults and the latter in children. Pathogenesis involves immune dysfunction with antibodies directed against erythroid precursor cells or erythropoietin, or due to T-cell mediated suppression of erythropoiesis.
Red cell pyruvate kinase deficiency is the most common cause of hereditary nonspherocytic hemolytic anemia. PK deficiency is also the most frequent enzyme abnormality of the glycolytic pathway (Zanella et al., 2005).
An autosomal recessive disorder caused by mutation of the NT5C3A gene. It is the most frequent abnormality of red cell nucleotide metabolism, causing chronic, non-spherocytic hemolytic anemia. Most affected individuals have Mediterranean, Jewish, or African ancestry. Basophilic stippling and accumulation of pyrimidines within erythrocytes are hallmarks of this disorder.
A form of neutropenia with congenital onset. [HPO:probinson]
MYH9-related disorders (MYH9RD) are characterized by large platelets (i.e., >40% of platelets >3.9 µm in diameter) and thrombocytopenia (platelet count <150 x 109/L), both of which are present from birth. MYH9RD is variably associated with young-adult onset of progressive sensorineural hearing loss, presenile cataract, elevation of liver enzymes, and renal disease manifesting initially as glomerular nephropathy. Before identification of the gene in which mutation is causative, MYH9, individuals with MYH9RD were diagnosed as having Epstein syndrome, Fechtner syndrome, May-Hegglin anomaly, or Sebastian syndrome based on the combination of different clinical findings at the time of diagnosis. However, the realization that they all are due to heterozygous pathogenic variants in MYH9 and that the clinical findings often worsen throughout life as a result of late onset of non-hematologic manifestations has led the four conditions to be regarded as one disorder, now known as MYH9RD.
Any abnormality of the alveolar ridges (on the upper or lower jaws). The alveolar ridges contain the sockets (alveoli) of the teeth.
A capillary hemangioma arising from the lip and presenting as a papular lesion.
Blisters or ulcers on the gums, lips and/or tongue caused by herpes virus.
Familial candidiasis is an inherited tendency to develop infections caused by a type of fungus called Candida. Affected individuals typically have infections of the skin, the nails, and the moist lining of body cavities (mucous membranes). These infections are recurrent and persistent, which means they come back repeatedly and can last a long time. This pattern of infection is called chronic mucocutaneous candidiasis.Candida is commonly present on the skin and on the mucous membranes, and in most people usually causes no health problems. However, certain medications (such as antibiotics and corticosteroids) and other factors can lead to occasional overgrowth of Candida (candidiasis) in the mouth (where it is known as thrush) or in the vagina. These episodes, commonly called yeast infections, usually last only a short time before being cleared by a healthy immune system.Most people with familial candidiasis have chronic or recurrent yeast infections that begin in early childhood. Skin infections lead to a rash with crusty, thickened patches; when these patches occur on the scalp, they can cause loss of hair in the affected area (scarring alopecia). Candidiasis of the nails can result in thick, cracked, and discolored nails and swelling and redness of the surrounding skin. Thrush and gastrointestinal symptoms such as bloating, constipation, or diarrhea are common in affected individuals. Women with familial candidiasis can develop frequent vaginal yeast infections, and infants can have yeast infections on the skin that cause persistent diaper rash.Depending on the genetic change involved in this condition, some affected individuals are at risk for developing systemic candidiasis, a more severe condition in which the infection spreads through the bloodstream to various organs including the brain and the meninges, which are the membranes covering the brain and spinal cord. Systemic candidiasis can be life-threatening.Chronic or recurrent yeast infections can occur in people without familial candidiasis. Some individuals experience recurrent candidiasis as part of a general susceptibility to infections because their immune systems are impaired by a disease such as acquired immune deficiency syndrome (AIDS) or severe combined immunodeficiency (SCID), medications, or other factors. Other individuals have syndromes such as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) or autosomal dominant hyper-IgE syndrome (AD-HIES) that include a tendency to develop candidiasis along with other signs and symptoms affecting various organs and systems of the body.
Allergic inflammation of the esophagus. Morphologically, it is characterized by the presence of eosinophils infiltrating the esophageal epithelium. Patients present with swallowing difficulty and heartburn.
An acute bacterial infection that affects the esophagus. Symptoms include severe pain on swallowing and retrosternal pain. Endoscopic examination reveals esophageal mucosal ulcerations and pseudomembranous formations.
Infection of the esophagus caused by fungi, most often candida albicans and candida tropicalis. It usually affects patients with immunodeficiency disorders or diabetes mellitus. Symptoms include dysphagia and pain on swallowing.
Viral infection of the esophagus. It often occurs in immunocompromised patients and it is caused by cytomegalovirus or herpes simplex virus. Symptoms include pain on swallowing, fever, and retrosternal burning.
A necrotic process affecting the gastric wall.
A non-neoplastic polyp that arises from the stomach and is characterized by the presence of connective tissue stroma overgrowth and cystic formations.
A rare hyperplastic lesion of Brunner's gland in the duodenum. Although it is usually asymptomatic and discovered incidentally during upper gastrointestinal endoscopy, it may cause hemorrhage.
Your small intestine is the longest part of your digestive system - about twenty feet long! It connects your stomach to your large intestine (or colon) and folds many times to fit inside your abdomen. Your small intestine does most of the digesting of the foods you eat. It has three areas called the duodenum, the ileum, and the jejunum. Problems with the small intestine can include:. -Bleeding. -Celiac disease. -Crohn's disease. -Infections. -Intestinal cancer. -Intestinal obstruction. -Irritable bowel syndrome. -Ulcers, such as peptic ulcer. Treatment of disorders of the small intestine depends on the cause.
A malabsorption syndrome characterized by collagenous mucosal lesions of the SMALL INTESTINE, atrophy of MICROVILLI, severe malabsorption, diarrhea, and MALNUTRITION often refractory to a gluten-free diet.
A rare autoimmune disorder that usually affects children. It is associated with the presence of circulating autoantibodies that act against the gut epithelial cells. It is characterized by diarrhea and weight loss due to malabsorption.
Microvillus inclusion disease (MVID) is characterized by onset of intractable life-threatening watery diarrhea during infancy. Two forms are recognized: early-onset MVID with diarrhea beginning in the neonatal period, and late-onset, with first symptoms appearing after 3 or 4 months of life. Definite diagnosis is made by transmission electron microscopy demonstrating shortening or absence of apical microvilli with pathognomonic microvillus inclusions in mature enterocytes and peripheral accumulation of periodic acid-Schiff (PAS)-positive granules or vesicles in immature enterocytes (Muller et al., 2008). The natural course of MVID is often fatal, but partial or total weaning from parenteral nutrition has been described. For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
The presence of a painless whitish patch on the anal mucosa. Histologic examination reveals hyperkeratosis and acanthosis.
Inflammation of the colon that is caused by Cytomegalovirus.
Inflammation of the colon resulting from irradiation.
An abnormal communication between the large intestine and another organ or cavity.
A hole (perforation) in the wall of the rectum.
Hepatic necrosis, inflammation, or scarring due to any cause that persists for more than 6 months. Manifestations may include signs and symptoms of cholestasis, portal hypertension, and/or abnormal liver function tests.
A non-metastasizing cystic epithelial neoplasm arising from the exocrine pancreas.
Leakage due to breakdown of a pancreatic anastomosis.
Peritonitis that is caused by a bacterial infection.
Leakage due to breakdown of a gastrointestinal anastomosis.
Leakage due to breakdown of an esophageal anastomosis.
Leakage due to breakdown of a gastric anastomosis.
An acute inflammation of the glomeruli, in which all glomeruli are affected, resulting in acute renal failure.
Fanconi Syndrome caused by exposure to noxious agents.
An inability of the tubules in the kidney to reabsorb small molecules, causing increased urinary loss of electrolytes (sodium, potassium, bicarbonate), minerals, glucose, amino acids, and water.
A urodynamic anomaly characterized by bladder outlet obstruction from detrusor muscle contraction with concomitant involuntary urethral sphincter activation.
Bleeding originating from the urinary bladder wall.
A benign or malignant neoplasm that affects the seminal vesicle. Representative examples include cystadenoma and adenocarcinoma.
Midline indentation or cleft of the scrotum.
A firm nodule on the skin of the scrotum that is caused by an accumulation of sebum resulting from sebaceous gland blockage.
A benign or malignant neoplasm that affects the scrotum.
A benign, borderline, or malignant tumor that originates from the surface epithelium of the ovary. It is composed of epithelial cells and stroma. Representative examples of benign tumors include serous cystadenoma, mucinous cystadenoma, and benign Brenner tumor. Representative examples of borderline tumors include serous surface papillary tumor, mucinous adenofibroma, and borderline Brenner tumor. Representative examples of malignant tumors include serous adenocarcinoma, mucinous adenocarcinoma, endometrioid adenocarcinoma, and malignant Brenner tumor.
A benign, human papillomavirus-related neoplasm that arises from the vulva and is characterized by the presence of papillary structures with fibrovascular cores covered by stratified squamous epithelium showing koilocytotic changes.
Adenomyosis is characterized by the presence of endometrial glands and stroma within the myometrium. Abnormal uterine bleeding and dysmenorrhea are the most characteristic symptoms, occurring in approximately 65% of cases (Arnold et al., 1995).
HYPERTENSION that develops as a result of PREGNANCY and regresses post partum. It is hypertension without PROTEINURIA or pathological EDEMA.
Preeclampsia with a systolic blood pressure of 160 mmHg or higher, or a diastolic blood pressure of 110 mmHg or higher on two occasions at least 4 hours apart while on bedrest. It is associated with thrombocytopenia (platelets less than 100,000 per microliter), impaired liver function (twice normal elevation of hepatic transaminases; severe, persistent right upper quadrant or epigastric pain), progressive renal insufficiency (serum creatinine greater than 1.1 mg/dL or doubling of baseline in the absence of other renal disease), pulmonary edema, or new-onset cerebral or visual disturbances.
A congenital or acquired deformity of the nipple.
Enlargement of the entire thyroid gland without discrete mass(es).
Severe, transient hyperthyroidism associated with Hashimoto thyroiditis.
Nodular enlargement of the thyroid gland associated with hyperthyroidism.
Incomplete development of the thyroid gland in a newborn.
Thyroid hormone deficiency present at birth that is associated with ectopic thyroid tissue located in the neck region.
Hypothyroidism characterized by elevated thyroid-stimulating hormone (TSH) with normal circulating concentrations of thyroid hormones.
A rare disorder characterized by the development of an abscess in the thyroid gland. It usually follows an upper respiratory tract, pharyngeal, or middle ear infection. It is usually caused by Staphylococcus or Streptococcus infection. It presents with fever, pain, and neck mass.
Familial dysalbuminemic hyperthyroxinemia is an autosomal dominant condition characterized by the presence of a variant serum albumin with preferential affinity for thyroxine (T4) in clinically euthyroid individuals. Individuals have consistently elevated total T4 and elevated or normal free T4 values with normal TSH levels. The condition may be confused with hyperthyroidism or thyroid hormone resistance syndromes, prompting repeated unnecessary laboratory testing and possibly even inappropriate treatment (summary by Heufelder et al., 1995).
An abnormal growth of parafollicular (C-cells) cells.
A defect in any step of the biochemical pathway leading to production of thyroid hormones.
Kanou et al. (2007) reviewed characteristics of thyroid dyshormonogenesis caused by mutations in the thyroglobulin (TG) gene. This form of thyroid dyshormonogenesis has an estimated prevalence of one in 100,000 newborns. Inherited in an autosomal recessive manner, the disorder in the majority of patients causes large goiters of elastic and soft consistency. Although the degree of thyroid dysfunction varies considerably among patients with defective TG synthesis, patients usually have a relatively high serum free T3 concentration with disproportionately low free T4 level. The maintenance of relatively high FT3 levels prevents profound tissue hypothyroidism except in brain and pituitary, which are dependent on T4 supply, resulting in neurologic and intellectual defects in some cases.
Presumed loss-of-function mutation(s) in the IYD gene, resulting in reduced activity of the enzyme iodotyrosine deiodinase.
A condition in which the pituitary gland is partially resistant to thyroid hormone, so that it continues to secrete thyroid-stimulating hormone (TSH) until the blood level of thyroid hormone rises higher than normal.
Severely reduced physical and mental growth associated with pyramidal and extrapyramidal signs and symptoms, due to dietary iodine deficiency.
Enlargement of the thyroid gland related to a singular nodule in the thyroid gland.
Enlargement of the thyroid gland related to multiple nodules in the thyroid gland.
Abnormally high levels of glucagon in the blood, which may manifest as hyperglycemia and/or necrolytic migratory erythema.
Impaired pancreatic secretion of glucagon that results in severely low blood glucose.
A group of disorders affecting the eye in patients with diabetes mellitus. It includes cataract, glaucoma, retinopathy, and blindness.
Conditions or pathological processes associated with the disease of diabetes mellitus. Due to the impaired control of BLOOD GLUCOSE level in diabetic patients, pathological processes develop in numerous tissues and organs including the EYE, the KIDNEY, the BLOOD VESSELS, and the NERVE TISSUE.
Hyperglycemia in the first month of life due to a genetically determined defect in the structure, secretion and/or function of insulin that resolves spontaneously within nine months of onset.
Maturity-onset diabetes of the young is an autosomal dominant form of diabetes typically occurring before 25 years of age and caused by primary insulin secretion defects. Despite its low prevalence, MODY is not a single entity but represents genetic, metabolic, and clinical heterogeneity (Vaxillaire and Froguel, 2008). Genetic Heterogeneity of MODY MODY1 (125850) is caused by heterozygous mutation in the hepatocyte nuclear factor-4-alpha gene (HNF4A; 600281) on chromosome 20. MODY2 (125851) is caused by heterozygous mutation in the glucokinase gene (GCK; 138079) on chromosome 7. MODY3 (600496) is caused by heterozygous mutation in the hepatocyte nuclear factor-1alpha gene (HNF1A; 142410) on chromosome 12q24.2. MODY4 (606392) is caused by heterozygous mutation in the pancreas/duodenum homeobox protein-1 gene (PDX1; 600733) on chromosome 13q12.1. MODY5 (137920) is caused by heterozygous mutation in the gene encoding hepatic transcription factor-2 (TCF2; 189907) on chromosome 17cen-q21.3. MODY6 (606394) is caused by heterozygous mutation in the NEUROD1 gene (601724) on chromosome 2q32. MODY7 (610508) is caused by heterozygous mutation in the KLF11 gene (603301) on chromosome 2p25. MODY8 (609812), or diabetes-pancreatic exocrine dysfunction syndrome, is caused by heterozygous mutation in the CEL gene (114840) on chromosome 9q34. MODY9 (612225) is caused by heterozygous mutation in the PAX4 gene (167413) on chromosome 7q32. MODY10 (613370) is caused by heterozygous mutation in the insulin gene (INS; 176730) on chromosome 11p15.5. MODY11 (613375) is caused by heterozygous mutation in the BLK gene (191305) on chromosome 8p23. MODY13 (616329) is caused by heterozygous mutation in the KCNJ11 gene (600937) on chromosome 11p15. MODY14 (616511) is caused by heterozygous mutation in the APPL1 gene (604299) on chromosome 3p14.
Monogenic diabetes caused by inactivating mutation(s) in the GCK gene, encoding glucokinase. Heterozygous GCK mutations may manifest as mild hyperglycemia, which is not progressive, and usually requires no treatment. Homozygous GCK mutations result in permanent neonatal diabetes.
Type A insulin resistance syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. In people with type A insulin resistance syndrome, insulin resistance impairs blood sugar regulation and ultimately leads to a condition called diabetes mellitus, in which blood sugar levels can become dangerously high.Severe insulin resistance also underlies the other signs and symptoms of type A insulin resistance syndrome. In affected females, the major features of the condition become apparent in adolescence. Many affected females do not begin menstruation by age 16 (primary amenorrhea) or their periods may be light and irregular (oligomenorrhea). They develop cysts on the ovaries and excessive body hair growth (hirsutism). Most affected females also develop a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Unlike most people with insulin resistance, females with type A insulin resistance syndrome are usually not overweight.The features of type A insulin resistance syndrome are more subtle in affected males. Some males have low blood sugar (hypoglycemia) as the only sign; others may also have acanthosis nigricans. In many cases, males with this condition come to medical attention only when they develop diabetes mellitus in adulthood.Type A insulin resistance syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Donohue syndrome and Rabson-Mendenhall syndrome, are considered part of a spectrum. Type A insulin resistance syndrome represents the mildest end of the spectrum: its features often do not become apparent until puberty or later, and it is generally not life-threatening.
Multiple synostoses syndrome is characterized by multiple joint fusions, usually commencing in the hands, conductive deafness, and characteristic facial features, including a broad, tubular-shaped nose and a thin upper vermilion. Other features include brachydactyly, hypoplastic or absent middle phalanges, radial head dislocation, and pectus carinatum (summary by Takahashi et al., 2001). Genetic Heterogeneity of Multiple Synostoses Syndrome Other forms of multiple synostoses syndrome include SYNS2 (610017), caused by mutation in the GDF5 gene (601146) on chromosome 20q11; SYNS3 (612961), caused by mutation in the FGF9 gene (600921) on chromosome 13q12; and SYNS4 (617898), caused by mutation in the GDF6 gene (601147) on chromosome 8q22.
Insulin (INS; 176730) is produced posttranslationally from its precursor molecule, proinsulin, by site-directed proteolysis in beta-cell granules. Conversion involves cleavage at pairs of basic residues that link both the insulin A and B chains to C-peptide. Human proinsulin conversion has a preferred sequential route, such that cleavage at the B-chain/C-peptide junction occurs first, producing des-31,32 split proinsulin as the major conversion intermediate. Under normal circumstances, proinsulin conversion is largely completed before secretion, and low plasma levels of intact proinsulin and conversion intermediates are found. Structural abnormalities in the proinsulin molecule can impair conversion, leading to the accumulation of proinsulin-like material in the circulation. Such defects show an autosomal dominant mode of inheritance and are the main cause of familial hyperproinsulinemia (summary by Warren-Perry et al., 1997).
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. Ten types and their associated genes are recognized. The age of onset ranges from infancy to late adulthood; the rate of progression varies. Cognitive decline occurs in some subtypes, but more often cognition is relatively spared. Cerebellar atrophy is a frequent finding in some subtypes.
Thiamine-responsive megaloblastic anemia syndrome (TRMA) is characterized by megaloblastic anemia, progressive sensorineural hearing loss, and diabetes mellitus. Onset of megaloblastic anemia occurs between infancy and adolescence. The anemia is corrected with thiamine treatment, but the red cells remain macrocytic, and anemia can recur when treatment is withdrawn. Progressive sensorineural hearing loss has generally been early and can be detected in toddlers; hearing loss is irreversible and may not be prevented by thiamine treatment. The diabetes mellitus is non-type I in nature, with age of onset from infancy to adolescence. Thiamine treatment may delay onset of diabetes in some individuals.
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome is characterized by systemic autoimmunity, typically beginning in the first year of life. Presentation is most commonly the clinical triad of watery diarrhea, endocrinopathy (most commonly insulin-dependent diabetes mellitus), and eczematous dermatitis. Most children have other autoimmune phenomena including cytopenias, autoimmune hepatitis, or nephropathy; lymphadenopathy, splenomegaly, alopecia, arthritis, and lung disease related to immune dysregulation have all been observed. Fetal presentation of IPEX includes hydrops, echogenic bowel, skin desquamation, IUGR, and fetal akinesia. Without aggressive immunosuppression or bone marrow transplantation, the majority of affected males die within the first one to two years of life from metabolic derangements, severe malabsorption, or sepsis; a few with a milder phenotype have survived into the second or third decade of life.
Maternally inherited diabetes-deafness syndrome (MIDD) is a mitochondrial disorder characterized by onset of sensorineural hearing loss and diabetes in adulthood. Some patients may have additional features observed in mitochondrial disorders, including pigmentary retinopathy, ptosis, cardiomyopathy, myopathy, renal problems, and neuropsychiatric symptoms (Ballinger et al., 1992; Reardon et al., 1992; Guillausseau et al., 2001). The association of diabetes and deafness is observed with Wolfram syndrome (see 222300), Rogers syndrome (249270), and Herrmann syndrome (172500), but all 3 of these disorders have other clinical manifestations.
Diabetes mellitus in which there are frequent, clinically significant fluctuations in blood glucose levels both above and below levels expected to be achieved by available therapies.
A syndrome of insulin resistance caused by mutation(s) in the INSR gene, encoding the insulin receptor. This condition is characterized by a clinical triad of hyperinsulinemia, acanthosis nigricans, and hyperandrogenism without lipodystrophy. This is the least severe of a spectrum of disorders; the other two conditions are Rabson-Mendenhall Syndrome and Donohoe Syndrome.
A condition of low or absent PTH level and HYPOCALCEMIA. It usually occurs as part of an autoimmune syndrome.
Hypoparathyroidism in which the inheritance is recessive and linked to the q26-q27 region of the X chromosome. The parathyroid glands are usually incompletely developed (parathyroid dysgenesis) or absent (parathyroid agenesis).
Autosomal dominant hypocalcemia-1 is associated with low or normal serum parathyroid hormone concentrations (PTH). Approximately 50% of patients have mild or asymptomatic hypocalcemia; about 50% have paresthesias, carpopedal spasm, and seizures; about 10% have hypercalciuria with nephrocalcinosis or kidney stones; and more than 35% have ectopic and basal ganglia calcifications (summary by Nesbit et al., 2013). Thakker (2001) noted that patients with gain-of-function mutations in the CASR gene, resulting in generally asymptomatic hypocalcemia with hypercalciuria, have low-normal serum PTH concentrations and have often been diagnosed with hypoparathyroidism because of the insensitivity of earlier PTH assays. Because treatment with vitamin D to correct the hypocalcemia in these patients causes hypercalciuria, nephrocalcinosis, and renal impairment, these patients need to be distinguished from those with other forms of hypoparathyroidism (see 146200). Thakker (2001) suggested the designation 'autosomal dominant hypocalcemic hypercalciuria' for this CASR-related disorder. Genetic Heterogeneity of Autosomal Dominant Hypocalcemia Autosomal dominant hypocalcemia-2 (HYPOC2; 615361) is caused by mutation in the GNA11 gene (139313) on chromosome 19p13.
An epithelium-lined, fluid-filled cyst containing parathyroid hormone that is usually located in an inferior parathyroid gland, but may be found in other locations in the neck or mediastinum.
Reduced spontaneous secretion of growth hormone with normal range response to growth hormone provocative stimuli.
Subnormal concentration of follicle stimulating hormone.
Subnormal concentration of luteinizing hormone.
A reduced ability to secrete adrenocorticotropic hormone (ACTH), a hormone that stimulates the adrenal cortex to secrete of glucocorticoids such as cortisol.
Ischemic necrosis of the pituitary gland.
An inflammatory process in the pituitary gland.
An autoimmune condition affecting the pituitary gland, characterized by lymphocytic infiltration, commonly presenting with pituitary hormone deficiencies.
A benign, disorganized mass of various mature cells, located heterotopically in the hypothalamus; it is often associated with endocrine and neurological conditions, such as precocious puberty and gelastic seizures.
A benign cyst located in the pituitary gland, containing fluid, tissue, or other material. It may be an incidental finding or present with headache, vision loss, or impaired pituitary gland function.
An abnormally increased size of the pituitary gland.
A milder form of congenital adrenal hyperplasia characterized by decreased activity of an enzyme in the steroidogenic pathway, typically presenting later in life, that does not require life-long cortisol replacement.
Classic 3-beta-hydroxysteroid dehydrogenase deficiency is an autosomal recessive form of CAH characterized by a severe impairment of steroid biosynthesis in both the adrenals and the gonads, resulting in decreased excretion of cortisol and aldosterone and of progesterone, androgens, and estrogens by these tissues. Affected newborns exhibit signs and symptoms of glucocorticoid and mineralocorticoid deficiencies, which may be fatal if not diagnosed and treated early, especially in the severe salt-wasting form. Moreover, male newborns exhibit pseudohermaphroditism with incomplete masculinization of the external genitalia due to an impairment of androgen biosynthesis in the testis. In contrast, affected females exhibit normal sexual differentiation or partial virilization (summary by Rheaume et al., 1992).
Lipoid congenital adrenal hyperplasia, the most severe disorder of steroid hormone biosynthesis, is caused by a defect in the conversion of cholesterol to pregnenolone, the first step in adrenal and gonadal steroidogenesis. All affected individuals are phenotypic females with a severe salt-losing syndrome that is fatal if not treated in early infancy (summary by Lin et al., 1991 and Bose et al., 1996).
Hypoaldosteronism characterized by impaired secretion of aldosterone, despite increased renin activity. This condition may be caused by chronic or critical illness, aldosterone synthase deficiency or other genetic conditions.
A hereditary disease characterized by childhood onset HYPERTENSION, hypokalemic alkalosis, and low RENIN and ALDOSTERONE secretion. It results from a defect in the activity of the 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 2 enzyme which results in inadequate conversion of CORTISOL to CORTISONE. The build up of unprocessed cortisol to levels that stimulate MINERALOCORTICOID RECEPTORS creates the appearance of having excessive MINERALOCORTICOIDS.
Congenital or acquired hyperplasia of the cells of the adrenal cortex.
Adrenal hyperfunction associated with multiple bilateral adrenal nodules, usually more than one centimeter in diameter.
Adrenal hyperfunction associated with multiple bilateral adrenal nodules, usually less than one centimeter in diameter.
An abnormal growth in the adrenal gland.
A cystic lesion located in the adrenal gland.
Testis not palpable in the scrotum or inguinal canal.
Inadequate production of circulating testosterone.
The onset of growth of pubic hair at an earlier age than normal.
An autosomal dominant hereditary disorder that is characterized by gonadotropin-dependent precocious puberty due to early activation of the hypothalamic-pituitary-gonadal axis. A mutation in the KISS1R gene has been identified. OMIM: 176400
Central precocious puberty for which no underlying cause can be identified.
Onset of adrenarche at an earlier age than usual.
Occurrence of the first menstrual period in a female before the usual or expected age.
Familial male precocious puberty is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. Affected males generally exhibit signs of puberty by age 4 years (Shenker et al., 1993).
Isolated growth hormone deficiency type IA is an autosomal recessive disorder characterized by severe growth failure (SDS less than -4.5) by 6 months of age, undetectable growth hormone (GH) concentrations, and a tendency to develop antibodies despite an initial good response to rhGH treatment (summary by Alatzoglou et al., 2014). Genetic Heterogeneity of Isolated Growth Hormone Deficiency See IGHD1B (617281) and IGHD2 (173100), both caused by mutation in the GH1 gene; IGHD3 (307200), caused by mutation in the BTK gene (300300); IGHD4 (618157), caused by mutation in the GHRHR gene (139191); and IGHD5 (618160), caused by mutation in the RNPC3 gene (618016).
Higher or lower than normal values for the serum electrolytes; usually affecting NA, K, CHL, CO2, glucose, bun.
Familial hypocalciuric hypercalcemia (HHC) is a heritable disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. HHC is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone (PTH; 168450) level. Hypermagnesemia is typically present. Individuals with HHC are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults (summary by Hannan et al., 2010). Characteristic features of familial hypocalciuric hypercalcemia include mild to moderate hypercalcemia, nonsuppressed parathyroid hormone, relative hypocalciuria while hypercalcemic (calcium/creatinine clearance ratio less than 0.01, or 24-hr urine calcium less than 6.25 mmol), almost 100% penetrance of hypercalcemia from birth, absence of complications, persistence of hypercalcemia following subtotal parathyroidectomy, and normal parathyroid size, weight, and histology at surgery. However, atypical presentations with severe hypercalcemia, hypercalciuria with or without nephrolithiasis or nephrocalcinosis, kindreds with affected members displaying either hypercalciuria or hypocalciuria, postoperative normocalcemia, and pancreatitis have all been described in FHH (Warner et al., 2004). Genetic Heterogeneity of Hypocalciuric Hypercalcemia Familial hypocalciuric hypercalcemia type II (HHC2; 145981) is caused by mutation in the GNA11 gene (139313) on chromosome 19p13, and HHC3 (600740) is caused by mutation in the AP2S1 gene (602242) on chromosome 19q13.
Autosomal dominant hypophosphatemic rickets is characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present with bone pain, rickets, and tooth abscesses. In contrast to X-linked dominant hypophosphatemic rickets (XLH; 307800), ADHR shows incomplete penetrance, variable age at onset (childhood to adult), and resolution of the phosphate-wasting defect in rare cases (Econs et al., 1997). See also hypophosphatemic bone disease (146350). Genetic Heterogeneity of Hypophosphatemic Rickets Other forms of hypophosphatemic rickets include an autosomal recessive forms, i.e., ARHR1 (241520), caused by mutation in the DMP1 gene (600980) on chromosome 4q21, and ARHR2 (613312), caused by mutation in the ENPP1 gene (173335) on chromosome 6q22-q23. An X-linked dominant form (307800) is caused by mutation in the PHEX gene (300550), and an X-linked recessive form (300554) is caused by mutation in the CLCN5 gene (300008). Clinical Variability of Hypophosphatemic Rickets Hypophosphatemic rickets can be caused by disorders of vitamin D metabolism or action (see VDDR1A, 264700). A form of hypophosphatemic rickets with hypercalciuria (HHRH; 241530) is caused by mutation in the SLC34A3 gene (609826), and there is evidence that a form of hypophosphatemic rickets with hyperparathyroidism (612089) may be caused by a translocation that results in an increase in alpha-klotho levels (KLOTHO; 604824).
An autosomal recessive renal phosphate wasting disorder that results in rickets.
Vitamin D-dependent rickets type 2A (VDDR2A) is caused by a defect in the vitamin D receptor gene. This defect leads to an increase in the circulating ligand, 1,25-dihydroxyvitamin D3. Most patients have total alopecia in addition to rickets. VDDR2B (600785) is a form of vitamin D-dependent rickets with a phenotype similar to VDDR2A but a normal vitamin D receptor, in which end-organ resistance to vitamin D has been shown to be caused by a nuclear ribonucleoprotein that interferes with the vitamin D receptor-DNA interaction. For a general phenotypic description and discussion of genetic heterogeneity of rickets due to disorders in vitamin D metabolism or action, see vitamin D-dependent rickets type 1A (VDDR1A; 264700).
Deposition of calcium in tissues outside of bone.
Abnormal calcification of the vasculature.
Calcified deposits in soft tissue structures outside a joint.
X-linked ocular albinism (XLOA) is a disorder of melanosome biogenesis leading to minor cutaneous and adnexal manifestations and congenital and persistent visual impairment in affected males. XLOA is characterized by infantile nystagmus, reduced visual acuity, hypopigmentation of the iris pigment epithelium and the ocular fundus, and foveal hypoplasia. Significant refractive errors, reduced or absent binocular functions, photoaversion, and strabismus are common. XLOA is a non-progressive disorder and the visual acuity remains stable throughout life, often slowly improving into the mid-teens.
Dopamine beta-hydroxylase (DBH) deficiency is characterized by lack of sympathetic noradrenergic function but normal parasympathetic and sympathetic cholinergic function. Affected individuals exhibit profound deficits in autonomic regulation of cardiovascular function that predispose to orthostatic hypotension. Although DBH deficiency appears to be present from birth, the diagnosis is not generally recognized until late childhood. The combination of ptosis of the eyelids in infants and children, together with hypotension, is suggestive of the disease. In the perinatal period, DBH deficiency has been complicated by vomiting, dehydration, hypotension, hypothermia, and hypoglycemia requiring repeated hospitalization; children have reduced exercise capacity. By early adulthood, individuals have profound orthostatic hypotension, greatly reduced exercise tolerance, ptosis of the eyelids, and nasal stuffiness. Presyncopal symptoms include dizziness, blurred vision, dyspnea, nuchal discomfort, and chest pain; symptoms may worsen in hot environments or after heavy meals or alcohol ingestion. Life expectancy is unknown, but some affected individuals have lived beyond age 60 years.
Transcobalamin II deficiency is an autosomal recessive disorder with onset in early infancy characterized by failure to thrive, megaloblastic anemia, and pancytopenia. Other features include methylmalonic aciduria, recurrent infections, and vomiting and diarrhea. Treatment with cobalamin results in clinical improvement, but the untreated disorder may result in mental retardation and neurologic abnormalities (summary by Haberle et al., 2009). Hall (1981) gave a clinically oriented review of congenital defects of vitamin B12 transport, and Frater-Schroder (1983) gave a genetically oriented review.
Hereditary folate malabsorption (HFM) is characterized by folate deficiency with impaired intestinal folate absorption and impaired folate transport into the central nervous system. Findings include poor feeding, failure to thrive, and anemia. There can be leukopenia and thrombocytopenia, diarrhea and/or oral mucositis, hypoimmunoglobulinemia, and other immunologic dysfunction resulting in infections, most often Pneumocystis jerovicii pneumonia. Neurologic manifestations include developmental delays, cognitive and motor impairment, behavioral disorders and, frequently, seizures.
GABA-transaminase deficiency is characterized by neonatal or early infantile-onset encephalopathy, hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth. Electroencephalograms show burst-suppression, modified hypsarrhythmia, multifocal spikes, and generalized spike-wave. Severity varies, but most patients have profound developmental impairment and some patients die in infancy (summary by Koenig et al., 2017).
3-methylglutaconyl-CoA hydratase deficiency is an inherited condition that causes neurological problems. Beginning in infancy to early childhood, children with this condition often have delayed development of mental and motor skills (psychomotor delay), speech delay, involuntary muscle cramping (dystonia), and spasms and weakness of the arms and legs (spastic quadriparesis). Affected individuals can also have optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain.In some cases, signs and symptoms of 3-methylglutaconyl-CoA hydratase deficiency begin in adulthood, often in a person's twenties or thirties. These individuals have damage to a type of brain tissue called white matter (leukoencephalopathy), which likely contributes to progressive problems with speech (dysarthria), difficulty coordinating movements (ataxia), stiffness (spasticity), optic atrophy, and a decline in intellectual function (dementia).Affected individuals who show symptoms of 3-methylglutaconyl-CoA hydratase deficiency in childhood often go on to develop leukoencephalopathy and other neurological problems in adulthood.All people with 3-methylglutaconyl-CoA hydratase deficiency accumulate large amounts of a substance called 3-methylglutaconic acid in their body fluids. As a result, they have elevated levels of acid in their blood (metabolic acidosis) and excrete large amounts of acid in their urine (aciduria). 3-methylglutaconyl-CoA hydratase deficiency is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with 3-methylglutaconyl-CoA hydratase deficiency also have high urine levels of another acid called 3-methylglutaric acid.
3-methylglutaconic aciduria inherited in an autosomal recessive pattern and caused by mutations in the AUH gene. Signs and symptoms include psychomotor developmental abnormalities, speech delay, weakness and spasm of the extremities, dystonia, and metabolic acidosis.
A very rare autosomal recessive disorder of cholesterol biosynthesis. It is caused by a deficiency of the enzyme mevalonate kinase, resulting in the accumulation of mevalonic acid in the urine. Signs and symptoms include psychomotor retardation, ataxia, recurrent fevers, skin rash, hepatosplenomegaly, and lymphadenopathy.
3-Hydroxyisobutyryl-CoA hydrolase deficiency is an autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia (summary by Ferdinandusse et al., 2013).
Primary trimethylaminuria is characterized by a fishy odor resembling that of rotten or decaying fish that results from excess excretion of trimethylamine in the urine, breath, sweat, and reproductive fluids. No physical symptoms are associated with trimethylaminuria. Affected individuals appear normal and healthy; however, the unpleasant odor often results in social and psychological problems. Symptoms are usually present from birth and may worsen during puberty. In females, symptoms are more severe just before and during menstruation, after taking oral contraceptives, and around the time of menopause.
Glycogen storage disease due to acid maltase deficiency (AMD) is an autosomal recessive trait leading to metabolic myopathy that affects cardiac and respiratory muscles in addition to skeletal muscle and other tissues. AMD represents a wide spectrum of clinical presentations caused by an accumulation of glycogen in lysosomes.
Glycogen storage disease due to acid maltase deficiency, late onset (AMDL), a form of Glycogen storage disease due to acid maltase deficiency (AMD), a degenerative metabolic myopathy particularly affecting respiratory and skeletal muscles, is characterised by an accumulation of glycogen in lysosomes.
An autosomal recessive genetic disorder caused by mutations in the GLYCTK gene, encoding glycerate kinase. The condition is characterized by excretion of D-glyceric acid in the urine. The phenotype varies from mild to severe, and may result in encephalopathy, mental retardation, microcephaly and early death.
Fumarate hydratase deficiency results in severe neonatal and early infantile encephalopathy that is characterized by poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Dysmorphic facial features include frontal bossing, depressed nasal bridge, and widely spaced eyes. Many affected individuals are microcephalic. A spectrum of brain abnormalities are seen on magnetic resonance imaging, including cerebral atrophy, enlarged ventricles and generous extra-axial cerebral spinal fluid (CSF) spaces, delayed myelination for age, thinning of the corpus callosum, and an abnormally small brain stem. Brain malformations including bilateral polymicrogyria and absence of the corpus callosum can also be observed. Development is severely affected: most affected individuals are non-verbal and non-ambulatory, and many die during early childhood. Less severely affected individuals with moderate cognitive impairment and long-term survival have been reported.
Most infants with short-chain acyl-CoA dehydrogenase deficiency (SCADD) identified through newborn screening programs have remained well, and asymptomatic relatives who meet diagnostic criteria are reported. Thus, SCADD is now viewed as a biochemical phenotype rather than a disease. A broad range of clinical findings was originally reported in those with confirmed SCADD, including severe dysmorphic facial features, feeding difficulties / failure to thrive, metabolic acidosis, ketotic hypoglycemia, lethargy, developmental delay, seizures, hypotonia, dystonia, and myopathy. However, individuals with no symptoms were also reported. In a large series of affected individuals detected on metabolic evaluation for developmental delay, 20% had failure to thrive, feeding difficulties, and hypotonia; 22% had seizures; and 30% had hypotonia without seizures. In contrast, the majority of infants with SCADD have been detected by expanded newborn screening, and the great majority of these infants remain asymptomatic. As with other fatty acid oxidation deficiencies, characteristic biochemical findings of SCADD may be absent except during times of physiologic stress such as fasting and illness. A diagnosis of SCADD based on clinical findings should not preclude additional testing to look for other causes.
Mitochondrial DNA (mtDNA) deletion syndromes predominantly comprise three overlapping phenotypes that are usually simplex (i.e., a single occurrence in a family), but rarely may be observed in different members of the same family or may evolve from one clinical syndrome to another in a given individual over time. The three classic phenotypes caused by mtDNA deletions are Kearns-Sayre syndrome (KSS), Pearson syndrome, and progressive external ophthalmoplegia (PEO). KSS is a progressive multisystem disorder defined by onset before age 20 years, pigmentary retinopathy, and PEO; additional features include cerebellar ataxia, impaired intellect (intellectual disability, dementia, or both), sensorineural hearing loss, ptosis, oropharyngeal and esophageal dysfunction, exercise intolerance, muscle weakness, cardiac conduction block, and endocrinopathy. Pearson syndrome is characterized by sideroblastic anemia and exocrine pancreas dysfunction and may be fatal in infancy without appropriate hematologic management. PEO is characterized by ptosis, impaired eye movements due to paralysis of the extraocular muscles (ophthalmoplegia), oropharyngeal weakness, and variably severe proximal limb weakness with exercise intolerance. Rarely, a mtDNA deletion can manifest as Leigh syndrome.
Systemic primary carnitine deficiency (CDSP) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. It encompasses a broad clinical spectrum including the following: Metabolic decompensation in infancy typically presenting between age three months and two years with episodes of hypoketotic hypoglycemia, poor feeding, irritability, lethargy, hepatomegaly, elevated liver transaminases, and hyperammonemia triggered by fasting or common illnesses such as upper respiratory tract infection or gastroenteritis. Childhood myopathy involving heart and skeletal muscle with onset between age two and four years. Pregnancy-related decreased stamina or exacerbation of cardiac arrhythmia. Fatigability in adulthood. Absence of symptoms. The latter two categories often include mothers diagnosed with CDSP after newborn screening has identified low carnitine levels in their infants.
Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder of long-chain fatty-acid oxidation. The three clinical presentations are lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form (which is usually mild and can manifest from infancy to adulthood). While the former two are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death, the latter is characterized by exercise-induced muscle pain and weakness, sometimes associated with myoglobinuria. The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. Males are more likely to be affected than females.
Carnitine-acylcarnitine translocase deficiency is a rare autosomal recessive metabolic disorder of long-chain fatty acid oxidation. Metabolic consequences include hypoketotic hypoglycemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical features include neurologic abnormalities, cardiomyopathy and arrhythmias, skeletal muscle damage, and liver dysfunction. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate. However, presentations at a later age with a milder phenotype have been reported (summary by Rubio-Gozalbo et al., 2004).
Ketone bodies are major vectors of energy transfer from the liver to extrahepatic tissues and are the main source of lipid-derived energy for the brain. Mitchell et al. (1995) reviewed medical aspects of ketone body metabolism, including the differential diagnosis of abnormalities. As the first step of ketone body utilization, succinyl-CoA:3-oxoacid CoA transferase (SCOT, or OXCT1; EC 2.8.3.5) catalyzes the reversible transfer of CoA from succinyl-CoA to acetoacetate.
Malonyl-CoA decarboxylase deficiency is an uncommon inherited metabolic disease. The characteristic phenotype is variable, but may include developmental delay in early childhood, seizures, hypotonia, diarrhea, vomiting, metabolic acidosis, hypoglycemia, ketosis, abnormal urinary compounds, lactic acidemia, and hypertrophic cardiomyopathy (Sweetman and Williams, 2001).
Inosine triphosphate pyrophosphohydrolase (ITPase) deficiency is a common inherited condition characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes (Sumi et al., 2002).
The thiopurines include azathioprine (a pro-drug for mercaptopurine), mercaptopurine and thioguanine. They are used to treat a variety of immunological disorders such as rheumatoid arthritis, non- Hodgkin lymphoma and ulcerative colitis. Both mercaptopurine and thioguanine can exert cytotoxic effects through the formation of thioguanine nucleotides (TGNs), active metabolites that incorporate into DNA. Mercaptopurine and thioguanine are directly inactivated by thiopurine S-methyltransferase (TPMT). Individuals with two nonfunctional TPMT alleles are at 100% risk of potentially fatal myelosuppression, due to an increased buildup of toxic TGNs. Alternative agents or a drastically reduced dose are recommended for patients with this genotype. Patients heterozygous for a nonfunctional TPMT allele are at increased risk of myelosuppression, and reduced dosing is recommended for these individuals. These dosing guidelines have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
DPYS deficiency is an autosomal recessive disease characterized by the presence of dihydropyrimidinuria. The clinical phenotype is highly variable, ranging from early infantile onset of severe neurologic involvement, dysmorphic features, and feeding problems to late onset of mild intellectual disability and even asymptomatic individuals. Patients with a complete or partial deficiency have an increased risk of developing severe toxicity after administration of the anticancer drug 5-fluorouracil (5-FU) (summary by Nakajima et al., 2017). See also dihydropyrimidine dehydrogenase deficiency (274270), a similar disorder.
Sialuria is a rare inborn error of metabolism in which excessive free sialic acid is synthesized. Clinical features include hepatosplenomegaly, coarse facial features, and varying degrees of developmental delay (summary by Enns et al., 2001).
D-bifunctional protein deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also peroxisomal acyl-CoA oxidase deficiency (264470), caused by mutation in the ACOX1 gene (609751) on chromosome 17q25. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including X-linked adrenoleukodystrophy (ALD; 300100), Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (NALD; see 601539) (Watkins et al., 1995). DBP deficiency has been classified into 3 subtypes depending upon the deficient enzyme activity. Type I is a deficiency of both 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase; type II is a deficiency of hydratase activity alone; and type III is a deficiency of dehydrogenase activity alone. Virtually all patients with types I, II, and III have a severe phenotype characterized by infantile-onset of hypotonia, seizures, and abnormal facial features, and most die before age 2 years. McMillan et al. (2012) proposed a type IV deficiency on the basis of less severe features; these patients have a phenotype reminiscent of Perrault syndrome (PRLTS1; 233400). Pierce et al. (2010) noted that Perrault syndrome and DBP deficiency overlap clinically and suggested that DBP deficiency may be underdiagnosed.
Glutaric aciduria III is characterized by an isolated accumulation of glutaric acid. It appears to be a 'non-disease' as it is found in healthy individuals and is associated with inconsistent symptoms in others (summary by Marlaire et al., 2014).
An elevated concentration of high-density lipoprotein cholesterol (HDL) in the blood.
abnormally decreased amount of fat in the blood.
Fish-eye disease, also called partial LCAT deficiency, is a disorder that causes the clear front surface of the eyes (the corneas) to gradually become cloudy. The cloudiness, which generally first appears in adolescence or early adulthood, consists of small grayish dots of cholesterol (opacities) distributed across the corneas. Cholesterol is a waxy, fat-like substance that is produced in the body and obtained from foods that come from animals; it aids in many functions of the body but can become harmful in excessive amounts. As fish-eye disease progresses, the corneal cloudiness worsens and can lead to severely impaired vision.
Sitosterolemia is characterized by: Tendon xanthomas or tuberous (i.e., planar) xanthomas that can occur in childhood and in unusual locations (heels, knees, elbows and buttocks); Premature atherosclerosis which can lead to angina, aortic valve involvement, myocardial infarction, and sudden death; Hemolytic anemia, abnormally shaped erythrocytes (stomatocytes), and large platelets (macrothrombocytopenia). On occasion, the abnormal hematologic findings may be the initial presentation. The phenotypic spectrum of sitosterolemia is probably not fully appreciated due to underdiagnosis and the fact that clinical findings in infants are likely to be highly dependent on diet.
A finding indicating an abnormal increase in the body's basal metabolic rate.
An infectious process affecting the nail.
A rare genetic disorder with an autosomal recessive pattern of inheritance. It is caused by the ineffective or decreased biosynthesis of the fifth complement component, C5. C5 deficiency may also be acquired acutely post-infection. If C5 is adequately synthesized, its rapid depletion may result in a functional deficiency. Clinical signs of the inherited deficiency present within the second decade of life and are consistent with the signs of recurrent systemic infection. Deficiency of serum C5 and its major cleavage product, C5b, a component of the membrane attack complex, increases susceptibility to Neisserial infections.
Generalized pustular psoriasis (GPP) is a life-threatening disease characterized by sudden, repeated episodes of high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis and elevated serum levels of C-reactive protein (123260) (summary by Marrakchi et al., 2011). GPP often presents in patients with existing or prior psoriasis vulgaris (PV; see 177900); however, GPP can develop without a history of PV (Sugiura et al., 2013). Palmoplantar pustulosis and acrodermatitis continua of Hallopeau represent acral forms of pustular psoriasis that have historically been grouped with GPP (summary by Setta-Kaffetzi et al., 2013). GPP in association with sterile multifocal osteomyelitis and periostitis (612852) is caused by mutation in the IL1RN gene (147679). Capon (2013) noted that the percentage of GPP patients reported to be negative for mutation in IL36RN ranges from 51 to 84%, indicative of genetic heterogeneity in the generalized pustular form of psoriasis. For a discussion of genetic heterogeneity of psoriasis, see PSORS1 (177900).
A raised, inflamed skin reaction to pressure from rubbing or scratching.
Familial cold autoinflammatory syndrome is a condition that causes episodes of fever, skin rash, and joint pain after exposure to cold temperatures. These episodes usually begin in infancy and occur throughout life.People with this condition usually experience symptoms after cold exposure of an hour or more, although in some individuals only a few minutes of exposure is required. Symptoms may be delayed for up to a few hours after the cold exposure. Episodes last an average of 12 hours, but may continue for up to 3 days.In people with familial cold autoinflammatory syndrome, the most common symptom that occurs during an episode is an itchy or burning rash. The rash usually begins on the face or extremities and spreads to the rest of the body. Occasionally swelling in the extremities may occur.In addition to the skin rash, episodes are characterized by fever, chills, and joint pain, most often affecting the hands, knees, and ankles. Redness in the whites of the eye (conjunctivitis), sweating, drowsiness, headache, thirst, and nausea may also occur during an episode of this disorder.
Multiple eruptive milia (MEM) is a rare condition in which clusters of milia (benign keratinous cysts) develop suddenly on the face and upper trunk (summary by Langley et al., 1997).
A capillary hemangioma of the skin, presenting as a red papular lesion.
A reactive, well-circumscribed vascular lesion. It is characterized by the formation of thin papillae projecting within the lumen of blood vessels. The papillae are lined by plump endothelial cells. Blood clots are also present.
An acute phenomenon characterized by hypotension and anasarca due to the loss of plasma volume into peripheral tissues, with evidence of decreased plasma volume (hemoconcentration) and protein loss from the intravascular space (hypoalbuminemia) during acute episodes.
A localized lymphangioma characterized by microcystic changes.
Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis (NFJS/DPR) represents a rare type of ectodermal dysplasia, a group of about 150 conditions characterized by abnormal development of ectodermal tissues including the skin, hair, nails, teeth, and sweat glands. NFJS and DPR were originally described as separate conditions; however, because they have similar features and are caused by mutations in the same gene, they are now often considered forms of the same disorder.Among the most common signs of NFJS/DPR is a net-like pattern of dark brown or gray skin coloring, known as reticulate hyperpigmentation. This darker pigmentation is seen most often on the neck, chest, and abdomen, although it can also occur in and around the eyes and mouth. Reticulate hyperpigmentation appears in infancy or early childhood. It may fade with age or persist throughout life.NFJS/DPR also affects the skin on the hands and feet. The skin on the palms of the hands and soles of the feet often becomes thick, hard, and callused, a condition known as palmoplantar keratoderma. Some affected individuals also have blistering on their palms and soles. Their fingernails and toenails may be malformed, brittle, and either thicker or thinner than usual. Most affected individuals are missing the patterned ridges on the skin of the hands and feet, called dermatoglyphs, that are the basis for each person's unique fingerprints.Additional features of NFJS/DPR can include a reduced ability to sweat (hypohidrosis) or excess sweating (hyperhidrosis) and dental abnormalities. Some affected individuals also have hair loss (alopecia) on the scalp, eyebrows, and underarms. The alopecia is described as noncicatricial because it does not leave scars (cicatrices).
A benign skin lesion consisting of a cluster of capillaries at the surface of the skin, forming a red papular lesion.
A variant of cutaneous mastocytosis which occurs as a single lesion usually in infants. It is found mostly in the wrist and trunk and there is no atypical cytomorphology.
Results from abnormal knee motion ( i.e. sliding of the bones} due to damage to ligament; as a result the knee becomes more and more unstable leading to pain, swelling and the potential for further injury.
A form of vasculitis that involves small to medium size arteries of the dermis and subcutaneous tissue. The disorder manifests with tender subcutaneous nodules, livedo reticularis, cutaneous ulcers and necrosis; while internal organ involvement is typically spared, extra-cutaneous symptoms may be present.
Mild hypotonia that usually appears early in infancy and has a favorable outcome. It is not a manifestation of another disorder that may cause hypotonia (e.g., cerebral palsy or muscular dystrophy).
A syndrome of generalized rigidity with muscle spasms and seizures in the neonatal period resulting from Clostridium tetani toxin production.
Paratyphoid fever that is caused by infection with Salmonella enterica, serovar Paratyphi A.
Paratyphoid fever that is caused by infection with Salmonella enterica, serovar Paratyphi B.
Paratyphoid fever that is caused by infection with Salmonella enterica, serovar Paratyphi C.
Inflammation of the stomach that is associated with Helicobacter Pylori.
A bacterial infection of the colon secondary to infection with Clostridium difficile bacteria. This infection generally results from the loss of normal gut flora secondary to recent antibiotic use, and manifests as copious watery stools, with associated abdominal pain and myalgia. C. difficile is the most common cause of pseudomembranous colitis, and can progress to toxic megacolon if left untreated.
A syndrome characterized by inflammation in the ILEUM, the CECUM, and the ASCENDING COLON. It is observed in cancer patients with CHEMOTHERAPY-induced NEUTROPENIA or in other immunocompromised individuals (IMMUNOCOMPROMISED HOST).
A protozoan infection that is caused by Cyclospora cayetanensis, which is most commonly acquired from contaminated food or water, and which is characterized by watery diarrhea and abdominal pain.
A bacterial infection that is caused by Staphylococcus aureus and is resistant to methicillin treatment.
Type 1 lepra reactions or reversal reactions are associated with the development of M. leprae antigenic determinants. They are delayed hypersensitivity reactions and may occur in both paucibacillary leprosy and multibacillary leprosy. (WHO)
Type 2 lepra reactions (erythema nodosum leprosum), are associated with circulation and tissue deposition of immune complexes. They are an antibody response or immune complex response to M. leprae antigenic determinants which occur only in multibacillary leprosy. (WHO)
Fixed sarcastic grimace and anxious expression. Caused by spasms of the masseter and other facial muscles.
A superinfection of the damaged oropharyngeal mucosa by FUSOBACTERIUM NECROPHORUM leading to the secondary septic THROMBOPHLEBITIS of the internal jugular vein.
A self-limited, febrile illness without pneumonia that occurs in epidemics, and that is caused by Legionella species.
A condition, whose clinical manifestations include intrauterine growth restriction, scarring cicatricial lesion of the limbs, abnormalities of the limbs, microcephaly, chorioretinitis, microphthalmia, cataracts, cortical atrophy, seizures, and evidence of damage to the autonomic nervous system, that is caused by fetal exposure to the varicella zoster virus during the first trimester of pregnancy.
A clinical variant of Burkitt lymphoma that occurs in equatorial Africa. The Epstein-Barr virus has been detected in all patients. It is the most common malignancy of childhood in this area.
An infectious process caused by a human papillomavirus. This infection can cause abnormal tissue growth.
Inflammation of the conjunctiva in a newborn due to Chlamydia trachomatis which was acquired during labor and delivery.
Involuntary weight loss of greater than 10 percent associated with intermittent or constant fever and chronic diarrhea or fatigue for more than 30 days in the absence of a defined cause other than HIV infection. A constant feature is major muscle wasting with scattered myofiber degeneration. A variety of etiologies, which vary among patients, contributes to this syndrome. (From Harrison's Principles of Internal Medicine, 13th ed, p1611).
An infection that is caused by Bartonella henselae, which occurs primarily in immunocompromised persons; it is characterized by blood-filled cysts in the liver and spleen.
An inflammatory skin condition in the diaper area superimposed with Candida infection, characterized by a bright red rash with a sharply demarcated edge and satellite lesions. Skin folds are often involved.
A fungal infection by any of the Candida species that is present at birth.
Fungal infections caused by TRICHOSPORON that may become systemic especially in an IMMUNOCOMPROMISED HOST. Clinical manifestations range from superficial cutaneous infections to systemic lesions in multiple organs.
OPPORTUNISTIC INFECTIONS caused by a heterogeneous group of MITOSPORIC FUNGI with clear (hyalo-) HYPHAE in the host. Common causative agents include ACREMONIUM; ASPERGILLUS; CHRYSOSPORIUM; FUSARIUM; PAECILOMYCES; PENICILLIUM; PSEUDALLESCHERIA; SCEDOSPORIUM; and SCOPULARIOPSIS. Normally a dermatomycoses, it can become invasive in the IMMUNOCOMPROMISED HOST.
A form of anaphylaxis that is triggered by exposure to venom. []
A form of anaphylaxis that is triggered by intake of drugs or medications. [PMID:29135486]
Anaphylaxis after physical activity. [PMID:7400473]
Blurred vision is the loss of visual acuity (sharpness of vision) resulting in a loss of ability to see small details. (from MedlinePlus Medical Encyclopedia)
A regional and pathological increase of the light detection threshold in any region of the visual field surrounded by a field of normal or relatively well-preserved vision.
Seesaw nystagmus is a type of pendular nystagmus where a half cycle consists of the elevation and intorsion of one eye, concurrently with the depression and extortion of the fellow eye. In the other half cycle, there is an inversion of the ocular movements.
A change in horizontal ocular alignment, unrelated to accommodation, that is brought about solely by a change in the balance of visual input from the two eyes. [PMID:18427617]
A conical projection of the anterior surface of the lens, occurring as a developmental anomaly.
A conical projection of the posterior surface of the lens, occurring as a developmental anomaly.
Ocular abnormality characterised by premature degeneration of the vitreous and the retina that may be associated with increased risk of retinal detachment.
A pale yellow discoloration of the temporal (lateral) portion of the optic disc.
The visible, linear scarring in the dermis, predominantly of the abdomen due to the stretching of tissue and related hormonal changes during pregnancy.
A triangular depigmented region of white hairs located in the anterior midline of the scalp.
An emotional state characterized by feelings of sadness, emptiness, and/or tearfulness.
An overwhelming, irrational, and persistent fear of traveling in an aircraft.
Failure of a physiologic function or system.
A type of vegetarian diet that excludes all animal products, including dairy, eggs, meat, poultry, fish, and animal fats.
An entwining of a segment of umbilical cord, usually without obstructing fetal circulation and commonly result from fetal slippage through a loop of the cord.
An involuntary muscular contraction in the stomach. Often, this cramp is spasmodic and can be uncomfortable.
An electrocardiographic finding of a wide QRS complex with evidence of delayed conduction to the right ventricle, manifested by a widened initial portion of the QRS in V1 and V2, a widened S wave in V5, V6, I and aVL, and with QRS duration greater than or equal to 120 ms. An RsR' complex is typically present in leads V1 and V2. (CDISC)
A type of ventricular tachycardia that is characterized by uniform QRS complexes within each lead (i.e., each QRS is identical or nearly so). []
A type of ventricular tachycardia that is characterized by variable QRS complexes within each lead (i.e., QRS complexes may be different from beat to beat). []
A pituitary prolactin cell adenoma of less than 10 mm diameter.
A pituitary prolactin cell adenoma of more than 10 mm diameter.
A primary or metastatic malignant neoplasm affecting the adrenal medulla.
A malignant tumor arising from the salivary gland. It includes carcinoma ex pleomorphic adenoma, a malignant epithelial tumor arising from a pre-existing pleomorphic adenoma and carcinosarcoma which is characterized by a mixture of malignant epithelial and sarcomatous elements.
A carcinoma arising in a pre-existing pleomorphic adenoma. It most often occurs in the parotid gland and less often in the submandibular gland and minor salivary gland. Patients usually present with a history of a long-standing mass which recently had undergone rapid growth. The prognosis depends on the invasiveness of the malignant component. Patients with non-invasive or minimally invasive tumors usually have a good prognosis following surgical resection. Invasive tumors are usually aggressive and are associated with recurrences and metastases.
An obsolete term referring to neoplasms arising from oligodendrocytes.
Underdevelopment of the corpus callosum.
Absence (aplasia) of the sacrum. [HPO:probinson]
A decrease in size of opening of the eye, not due to eyelid fusion, but rather lateral displacement of the inner canthi
Redundant eyelid skin pressing the eyelashes against the cornea and/or conjunctiva.
A developmental disorder of the lacrimal drainage system that most often affects the lacrimal ostium and resulting in non-opening of the nasolacrimal duct. It usually results from a non-canalization of the nasolacrimal duct.
A sectoral indentation of the crystalline lens, usually due to zonular weakness or absence.
Cerulean cataract, first described by Vogt (1922), is an autosomal dominant, early-onset, bilateral cataract with complete penetrance. Newborns appear asymptomatic until the age of 18 to 24 months, at which time they can be clinically diagnosed by slit-lamp examination through the appearance of tiny blue or white opacities that form first in the superficial layers of the fetal lens nucleus. The opacities progress throughout the adult lens nucleus and the cortex, forming concentric layers, with central lesions oriented radially. Histologically the lesions appear to be tapered cavities between lens fibers. Progression of the cataract is slow, such that patients may have lens extractions between the ages of 16 and 35 years (Armitage et al., 1995). The preferred title/symbol of this entry was formerly 'Cataract, Congenital, Cerulean Type, 1; CCA1.'
Cornea plana is an abnormally flat shape of the cornea such that the normal protrusion of the cornea from the sclera is missing. The reduced corneal curvature can lead to hyperopia, and a hazy corneal limbus and arcus lipoides may develop at an early age.
Megalocornea is an inherited eye disorder in which the corneal diameter is bilaterally enlarged (greater than 13 mm) without an increase in intraocular pressure. It may also be referred to as 'anterior megalophthalmos,' since the entire anterior segment is larger than normal. Features of megalocornea in addition to a deep anterior chamber include astigmatic refractive errors, atrophy of the iris stroma, miosis secondary to decreased function of the dilator muscle, iridodonesis, and tremulousness, subluxation, or dislocation of the lens. Whereas most affected individuals exhibit normal ocular function, complications include cataract development and glaucoma following lenticular dislocation or subluxation. X-linked recessive inheritance is the most common pattern, accounting for the male preponderance of the disorder (summary by Skuta et al., 1983). Megalocornea sometimes occurs as part of the Marfan syndrome (154700). Genetic Heterogeneity of Megalocornea Autosomal recessive megalocornea has been reported (249300).
Congenital underdevelopment of the iris.
The presence of remnants of a fetal membrane that persist as strands of tissue crossing the pupil.
An area of the retina that is buckled so that a sector-shaped sheet of retina lies in front of the normal retina. This feature is of congenital onset.
A form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs. Peters anomaly is characterized by central, paracentral, or complete corneal opacity.
A congenital anatomic anomaly in which the heart has only three chambers.
An abnormality of the circulatory connection between atria and ventricles.
Connection of the right atrium to the left ventricle and of the left atrium to the right ventricle in a biventricular heart.
The essence of the lesion is the combination of discordant atrioventricular and ventriculo-arterial connections. Thus, the morphologically right atrium is connected to a morphologically left ventricle across the mitral valve, with the left ventricle then connected to the pulmonary trunk. The morphologically left atrium is connected to the morphologically right ventricle across the tricuspid valve, with the morphologically right ventricle connected to the aorta.
With left or right cardiac isomerism in a biventricular, the atrioventricular connections are perforce ambiguous, in that one of the connections is concordant (e.g., right-sided morphologic right atrium connected to a morphologic right ventricle) and one of the connections is discordant (e.g., left-sided morphologic right atrium connected to a morphologic left ventricle).
The condition in which both atria are joined to the right ventricle each by its own atrioventricular valve. Usually, the left ventricle is hypoplastic.
The condition in which both atria are joined to the left ventricle each by its own atrioventricular valve. Usually there is a hypoplastic right ventricle, which may be on the opposite side of the heart as usual.
A defect where there is no connection between the right atrium and right ventricle.
A defect where there is no connection between the left atrium and left ventricle.
Absence of the right superior vena cava (RSVC). An absent RSVC is always associated with a persistent left superior vena cava (PLSVC). During normal fetal development, the left-sided anterior venous cardinal system regresses, leaving the coronary sinus (CS) and the ligament of Marshall. Failure of the closure of the left anterior cardinal vein results in PLSVC. In general, PLSVC is associated with the right superior vena cava (RSVC) and drains into the RA via a dilated CS. When developmental arrest occurs at an earlier stage, the CS is absent and the PLSVC drains into the left atrium.
An abnormality of the coronary sinus, which is formed by the union of the great cardiac vein and the left marginal vein and terminates in the right atrium. The coronary sinus functions to o collect deoxygenated blood from the myocardium of the heart and drain it into the right atrium.
A congenital defect of the vasculature such that there is a shunt (by-pass) of blood directly from the portal vein to the vena cava (i.e., the blood from the portal vein is not filtered through the liver).
A congenital anomaly with partitioning of the right atrium to form a triatrial heart caused by persistence of the right valve of the sinus venosus. Typically, the right atrial partition is due to exaggerated fetal eustachian and thebesian valves, which together form an incomplete septum across the lower part of the atrium. This septum may range from a reticulum to a substantial sheet of tissue.
An abnormality of the interatrial septum.
A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum.
An interatrial communication caused by a deficiency of the common wall between the superior vena cava (SVC) and the right-sided pulmonary veins. SVASD is commonly associated with anomalous pulmonary venous connection (APVC) of some or all of the pulmonary veins, which produces additional left-to-right shunting.
An ostium primum atrial septal defect is located in the most anterior and inferior aspect of the atrial septum. The ostium primum refers to an anterior and inferior opening (ostium) within the septum primum, which divides the rudimentary atrium during fetal development. The ostium primum is normally sealed by fusion of the superior and inferior endocardial cushions around 5 weeks' gestation. Ostium primum defects result from a failure of the fusion of the embryologic endocardial cushion and septum primum.
A form of agenesis of the tricuspid valve in which (although the normal orifice between the right atrium and right ventricle exists) there is no tricuspid valvular tissue.
A congenital defect with failure to open of the mitral valve orifice.
The left atrio-ventricular connection consists of two anatomically distinct orifices separated by accessory fibrous tissue.
The commonest form of tetralogy of Fallot characterized by pulmonary stenosis, overriding aorta, ventricular septum defect, and right ventricular hypertrophy, without pulmonary atresia, absent pulmonary valve, atrioventricular canal defect or absent subarterial conus.
An extreme form of tetralogy of Fallot characterized by absence of flow from the right ventricle to the pulmonary arteries.
An abnormality of the right ventricle of the heart.
Enlargement of the chamber of the right ventricle.
Any structural abnormality of the left ventricle of the heart.
An abnormality of the outflow tract of the left ventricle.
Obstruction of the left ventricular outflow tract. It is caused by aortic valve, supravalvar, or subvalvar defects.
Any ventricular septal defect (VSD) that is small enough to restrict flow across it such that a pressure gradient exists between the two sides of the VSD.
A congenital heart defect resulting from deficient growth or failure of fusion of the membranous component of the ventricular septum.
The more common indirect type of communication where the flow of blood is from the left ventricle through a ventricular septal defect into the right ventricle and then through a defect in the tricuspid valve into the right atrium.
A bowing (bulding to one side) of the interventricular septum of more than 15 mm on either side in adults and 5 mm in children during normal cardiac motion.
A rare congenital cardiovascular disorder characterized by severe underdevelopment of the right side of the heart. The infants develop cyanosis shortly after birth. It is a condition that requires immediate emergency treatment.
The presence of a bicuspid pulmonary valve.
The presence of an aortic valve with one instead of the normal three cusps (flaps).
The presence of an aortic valve with four instead of the normal three cusps (flaps). [PMID:27390747]
Stenosis of a peripheral branch of the pulmonary artery.
The right pulmonary artery originates from the ascending aorta in the presence of a pulmonary valve and main pulmonary artery.
The left pulmonary artery originates from the ascending aorta in the presence of a pulmonary valve and main pulmonary artery.
An abnormal localized widening (dilatation) of the tubular part of the ascending aorta.
Aneurysms and dissections of the aorta usually result from degenerative changes in the aortic wall. Thoracic aortic aneurysms and dissections are primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance. In contrast, degeneration leading to abdominal aortic aneurysm (100070) is usually caused by a combination of factors including age, atherosclerosis, hypertension, and infectious, inflammatory, or autoimmune processes. Medial necrosis and thoracic aortic aneurysm/dissection are known to occur in certain connective tissue diseases such as Marfan syndrome (154700), and vascular (type IV) Ehlers-Danlos syndrome (130050). More commonly, however, medial necrosis occurs in the absence of a clearly identifiable syndrome. Genetic Heterogeneity of Thoracic Aortic Aneurysm Loci for isolated thoracic aortic aneurysm have been identified on chromosomes 11q (AAT1) and 5q (AAT2; 607087). Mutation in the MYH11 gene (160745) on chromosome 16p causes AAT4 (132900). Mutation in the ACTA2 gene (102620) on chromosome 10q causes AAT6 (611788). Mutation in the MYLK gene (600922) on chromosome 3q21 causes AAT7 (613780). Mutation in the PRKG1 gene (176894) on chromosome 10q11 causes AAT8 (615436). Mutation in the MFAP5 gene (601103) on chromosome 12p13 causes AAT9 (616166). Mutation in the LOX gene (153455) on chromosome 5q23 causes AAT10 (617168). Mutation in the FOXE3 gene (601094) on chromosome 1p33 causes susceptibility to AAT11 (617349). Thoracic aortic aneurysm with dissection (e.g., AAT3 and AAT5) can occur as a manifestation of the Loeys-Dietz syndrome (see LDS2, 610168 and LDS1, 609192, caused by mutation in the TGFBR2 (190182) and TGFBR1 (190181) genes, respectively). Reviews Pyeritz (2014) reviewed heritable thoracic aortic disorders with particular attention to causative genes, including components of the extracellular matrix, vascular smooth muscle cytoskeleton, and TGF-beta and other signaling pathways.
The aortic arch extends into the soft tissues of the neck before turning down into to become the descending aorta.
Pseudocoarctation is a congenital anomaly of kinking, or buckling, of the aorta without a pressure gradient across the lesion. It is characterized by elongation and kinking of the aorta at the level of the ligamentum arteriosum.
Non-continuity of the aortic arch with an atretic point or absent segment at the level of the isthmus.
Non-continuity of the aortic arch with an atretic point or absent segment between the left carotid and subclavian arteries.
Non-continuity of the aortic arch with an atretic point or absent segment between the innominate and left carotid arteries.
Any abnormality involving the pericardium.
No pericardium around the heart, occurring as a congenital defect, not the result of a surgical pericardectomy.
Narrowing of the lumen of the jejunum that is present at birth.
Narrowing of the lumen of the ileum that is present at birth.
Abnormal small intestinal contractions, such as spasms and intestinal paralysis related to the loss of the ability of the gut to coordinate muscular activity because of endogenous or exogenous causes.
A malformation characterized by the absence of a normal opening in a part of the large intestine.
Cloacal exstrophy is a severe anterior abdominal wall defect in which the two hemibladders are visible and are separated by a midline intestinal plate, an omphalocele, and an imperforate anus.
Congenital malformations in the anorectal region that include the perineal fistula, anteriorly placed anus, and anorecto-vestibular fistula.
The most common form of Hirschsprung Disease, this is characterized by a lack of nerve cells in the sigmoid colon and rectum. The bowel is not stimulated without innervation and obstruction ensues. Surgical intervention is necessary.
A complete lack of ganglia in the intestine. This is an extremely severe form of Hirschsprung Disease.
The presence of peritoneal attachments (bands) that obstruct the duodenum. The attachments result from malrotation of the large intestine. This abnormality is manifested with severe vomiting soon after birth or after the first feeding of the infant.
The presence of a hypoplastic gallbladder.
Formation of abnormal lobules (small masses of tissue) in the liver.
A congenital defect in which the vagina is underdeveloped.
A cyst that is attached to the fallopian tube and originates from the remnants of the Mullerian duct.
Two penile structures, separated from the tip to the base of the shaft.
Congenital fusion of the embryonic kidneys forming a single renal parenchymal mass.
Persistence of the urachal canal with drainage of urine from the bladder through the persistent allantois canal to the umbilicus.
A form of polydactyly in which the extra digit or digits are localized on the side of the thumb or great toe.
Leg shortening because of underdevelopment of one or more bones of the lower extremity.
Osteopetrosis is a bone disease that makes bones abnormally dense and prone to breakage (fracture). Researchers have described several major types of osteopetrosis, which are usually distinguished by their pattern of inheritance: autosomal dominant, autosomal recessive, or X-linked. The different types of the disorder can also be distinguished by the severity of their signs and symptoms.Autosomal dominant osteopetrosis (ADO), which is also called Albers-Schönberg disease, is typically the mildest type of the disorder. Some affected individuals have no symptoms. In these people, the unusually dense bones may be discovered by accident when an x-ray is done for another reason. In affected individuals who develop signs and symptoms, the major features of the condition include multiple bone fractures, abnormal side-to-side curvature of the spine (scoliosis) or other spinal abnormalities, arthritis in the hips, and a bone infection called osteomyelitis. These problems usually become apparent in late childhood or adolescence.Autosomal recessive osteopetrosis (ARO) is a more severe form of the disorder that becomes apparent in early infancy. Affected individuals have a high risk of bone fracture resulting from seemingly minor bumps and falls. Their abnormally dense skull bones pinch nerves in the head and face (cranial nerves), often resulting in vision loss, hearing loss, and paralysis of facial muscles. Dense bones can also impair the function of bone marrow, preventing it from producing new blood cells and immune system cells. As a result, people with severe osteopetrosis are at risk of abnormal bleeding, a shortage of red blood cells (anemia), and recurrent infections. In the most severe cases, these bone marrow abnormalities can be life-threatening in infancy or early childhood.Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and spleen (hepatosplenomegaly). Depending on the genetic changes involved, people with severe osteopetrosis can also have brain abnormalities, intellectual disability, or recurrent seizures (epilepsy).A few individuals have been diagnosed with intermediate autosomal osteopetrosis (IAO), a form of the disorder that can have either an autosomal dominant or an autosomal recessive pattern of inheritance. The signs and symptoms of this condition become noticeable in childhood and include an increased risk of bone fracture and anemia. People with this form of the disorder typically do not have life-threatening bone marrow abnormalities. However, some affected individuals have had abnormal calcium deposits (calcifications) in the brain, intellectual disability, and a form of kidney disease called renal tubular acidosis.Rarely, osteopetrosis can have an X-linked pattern of inheritance. In addition to abnormally dense bones, the X-linked form of the disorder is characterized by abnormal swelling caused by a buildup of fluid (lymphedema) and a condition called anhydrotic ectodermal dysplasia that affects the skin, hair, teeth, and sweat glands. Affected individuals also have a malfunctioning immune system (immunodeficiency), which allows severe, recurrent infections to develop. Researchers often refer to this condition as OL-EDA-ID, an acronym derived from each of the major features of the disorder.
Digital clubbing is characterized by enlargement of the nail plate and terminal segments of the fingers and toes, resulting from proliferation of the connective tissues between the nail matrix and the distal phalanx (Myers and Farquhar, 2001).
A congenital vascular malformation that presents as localized or generalized erythematous-telangiectatic lesions with a reticular pattern; the lesions are almost always present at birth or develop in the first days of life. Cutis marmorata telangiectatica congenita (CMTC) appears as marble-like pattern (mottling) on the surface of the skin. In contrast to cutis marmorata, the marbling is more severe and always visible.
A benign or malignant neoplasm that affects the base of the tongue.
A carcinoma of the oral cavity that arises from the upper gingiva.
A carcinoma of the oral cavity that arises from the lower gingiva.
A benign or malignant neoplasm that affects the floor of the mouth.
A carcinoma that arises from the hard palate. Representative examples include squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma.
A non-metastasizing neoplasm that arises from the hard palate.
A carcinoma that arises from the soft palate. The majority are squamous cell carcinomas.
A non-metastasizing neoplasm that arises from the soft palate or uvula.
A non-metastasizing neoplasm that arises from the uvula.
A benign or malignant neoplasm that affects the buccal mucosa.
A non-metastasizing neoplasm that arises from the buccal mucosa.
A benign or malignant neoplasm that affects the major salivary glands. Representative examples of benign neoplasms include Warthin tumor, monomorphic adenoma, and pleomorphic adenoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma.
A carcinoma that arises from the parotid gland. Representative examples include mucoepidermoid carcinoma, adenoid cystic carcinoma, adenocarcinoma, and carcinoma ex pleomorphic adenoma.
A benign or malignant neoplasm that arises from the parotid gland. It is characterized by the presence of epithelial and mesenchymal elements. This category includes pleomorphic adenoma, carcinoma ex pleomorphic adenoma, and carcinosarcoma.
A carcinoma that arises from the submandibular gland. Representative examples include mucoepidermoid carcinoma, adenoid cystic carcinoma, and carcinoma ex pleomorphic adenoma.
A carcinoma that arises from the sublingual gland. Representative examples include cystadenocarcinoma and mucoepidermoid carcinoma.
A non-metastasizing neoplasm that arises from the base of the tongue.
A benign or malignant neoplasm that affects the minor salivary glands.
A primary or metastatic malignant neoplasm that affects the minor salivary glands. Representative examples include carcinoma and malignant mixed tumor.
A non-metastasizing neoplasm that arises from the minor salivary glands.
A benign or malignant neoplasm that affects the middle ear. Representative examples include adenoma, paraganglioma, and carcinoma.
A benign or malignant neoplasm that affects the nasal cavity. Representative examples of benign neoplasms include Schneiderian papilloma and salivary gland-type adenoma. Representative examples of malignant neoplasms include carcinoma and lymphoma.
A non-metastasizing neoplasm that arises from the maxillary sinus.
A benign or malignant neoplasm that affects the ethmoid sinus. Representative examples of benign neoplasms include Schneiderian papilloma and salivary gland-type adenoma. Representative examples of malignant neoplasms include carcinoma and lymphoma.
A non-metastasizing neoplasm that arises from the ethmoid sinus.
A benign or malignant neoplasm that affects the frontal sinus. Representative examples of benign neoplasms include Schneiderian papilloma and salivary gland-type adenoma. Representative examples of malignant neoplasms include carcinoma and lymphoma.
A non-metastasizing neoplasm that arises from the frontal sinus.
A benign or malignant neoplasm that affects the sphenoid sinus. Representative examples of benign neoplasms include Schneiderian papilloma and salivary gland-type adenoma. Representative examples of malignant neoplasms include carcinoma and lymphoma.
A non-metastasizing neoplasm that arises from the sphenoid sinus.
A benign or malignant neoplasm that affects the pyriform sinus.
A benign or malignant neoplasm that affects the glottic area of the larynx.
A benign or malignant neoplasm that affects the supraglottic area of the larynx.
A benign or malignant neoplasm that affects the subglottic area of the larynx.
A non-metastasizing neoplasm that arises from the subglottis.
A carcinoma that arises from the fundus of the stomach.
A carcinoma that arises from the body of the stomach.
A benign or malignant neoplasm that affects the small intestine. Representative examples of benign neoplasms include lipoma and leiomyoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma.
A benign or malignant neoplasm that affects the rectosigmoid region. Representative examples of benign neoplasms include lipoma and leiomyoma. Representative examples of malignant neoplasms include carcinoma, lymphoma, and sarcoma. Rectosigmoid adenomas always exhibit epithelial dysplasia and are considered premalignant neoplasms.
Juvenile polyposis syndrome (JPS) is characterized by predisposition to hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term ""juvenile"" refers to the type of polyp rather than to the age of onset of polyps. Most individuals with JPS have some polyps by age 20 years; some may have only four or five polyps over their lifetime, whereas others in the same family may have more than 100. If the polyps are left untreated, they may cause bleeding and anemia. Most juvenile polyps are benign; however, malignant transformation can occur. Risk for GI cancers in families with JPS ranges from 9% to 50%. Most of this increased risk is attributed to colon cancer, but cancers of the stomach, upper GI tract, and pancreas have also been reported. A combined syndrome of JPS and hereditary hemorrhagic telangiectasia (JPS/HHT) is present in most individuals with an SMAD4 pathogenic variant.
A non-neoplastic polypoid lesion that arises from the anal canal or perianal skin. It is composed of dense fibrous stroma and it is covered by squamous epithelium.
A tumor (abnormal growth of tissue) of the liver.
A carcinoma that arises from the intrahepatic bile duct epithelium in any site of the intrahepatic biliary tree. Grossly, the malignant lesions are solid, nodular, and grayish. Morphologically, the vast majority of cases are adenocarcinomas. Signs and symptoms include malaise, weight loss, right upper quadrant abdominal pain, and night sweats. Early detection is difficult and the prognosis is generally poor.
A malignant soft tissue neoplasm that arises from the liver. Representative examples include angiosarcoma, undifferentiated (embryonal) sarcoma, rhabdomyosarcoma, and leiomyosarcoma.
A malignant vascular neoplasm arising from the liver.
A non-metastasizing neoplasm arising from the gallbladder wall.
A benign or malignant neoplasm that affects the extrahepatic bile ducts. Representative examples include adenoma and adenocarcinoma.
Stage 0 includes: (Tis, N0, M0). Tis: Carcinoma in situ. N0: No regional metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
A benign or malignant neoplasm involving the ampulla of Vater.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
A benign or malignant neoplasm that arises from the epithelial cells of the exocrine pancreatic tissue.
A usually slow-growing, grade 1 pancreatic neuroendocrine tumor that secretes serotonin. When it metastasizes to the liver, it produces the clinical symptoms of the carcinoid syndrome.
An adenoid cystic carcinoma that arises from the trachea. It spreads to the submucosal tracheal tissue and to regional lymph nodes.
A rare squamous cell carcinoma that arises from the mucosal lining of the trachea. It usually grows as an intraluminal mass and later invades extraluminal structures. The majority of patients present with hemoptysis, coughing, dyspnea, or stridor.
A type of non-small cell lung carcinoma that is derived from undifferentiated malignant neoplasms originating from transformed epithelial cells in the lung, and which is differentiate from small-cell lung carcinoma by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of salt-and-pepper appearance of the chromatin.
A morphologic variant of lung sarcomatoid carcinoma characterized by the presence of mononuclear and multinucleated pleomorphic neoplastic giant cells that lack cohesion.
A low-grade malignant blood vessel neoplasm arising from the lung. It is characterized by the presence of epithelioid endothelial cells. The neoplastic cells are arranged in cords and nests, which are embedded in a myxoid to hyalinized stroma.
A non-metastasizing neoplasm that arises from the lung parenchyma or the bronchi. Representative examples include lung adenoma, lung hamartoma, and endobronchial lipoma.
A benign, well circumscribed epithelial neoplasm that arises from the bronchus or the lung parenchyma. Representative examples include alveolar adenoma, papillary adenoma, and mucus gland adenoma.
A benign or malignant teratoma that arises from the lung.
Malignant mesothelioma is an aggressive neoplasm of the serosal lining of the chest etiologically linked to asbestos. It is diagnosed in approximately 2,000 to 3,000 individuals annually in the United States, most of whom die within 2 years of diagnosis (summary by Bott et al., 2011). See also 614327 for a tumor predisposition syndrome that may contribute to the development of malignant mesothelioma upon asbestos exposure and is caused by germline mutation in the BAP1 gene (603089) on chromosome 3p21.
A non-metastasizing neoplasm that arises from the thymus.
A squamous cell carcinoma of the skin with a prominent clear cell component.
A histologic variant of squamous cell carcinoma that arises from the skin. It is characterized by loosening of the intercellular bridges between the malignant cells which results in acantholysis.
A rare genetic neoplastic disorder with an autosomal dominant pattern of inheritance characterized by multiple, recurrent skin cancers that spontaneously resolve. It has been described almost exclusively in families of Scottish origin. It is caused by a mutation in the tumor-suppressing gene, TGFBR1, on chromosome 9. Clinical presentation is usually rapidly growing squamous cell carcinomas or keratoacanthomas that primarily localize to sun-exposed areas. Appearance of the neoplasms occurs over several weeks before receding over the course of several months if untreated. The regression of the lesions leaves pitting cicatrices but no other known sequelae.
A benign or malignant neoplasm that arises from the hair follicles, sebaceous glands, or sweat glands.
A neoplasm with tricholemmal differentiation. It affects women more frequently than men. It usually presents on the scalp as a solitary, multilobular, large, exophytic mass. Morphologically, it may display benign cytological features and appear as a circumscribed solid-cystic neoplasm or it may display malignant characteristics and invasive features. Cases without malignant characteristics usually have an indolent course. Complete surgical excision is recommended in such cases to avoid recurrences and to allow complete examination of the specimen. Cases with malignant characteristics may have a locally aggressive clinical course, recur, or metastasize.
Presence of multiple small cysts containing keratin (skin protein) and presenting as tiny pearly-white bumps just under the surface of the skin.
A cutaneous cyst that is small (one or two millimeters in diameter) and painless, presenting as a follicular papule that usually is skin colored but may have a reddish or\nbrownish tinge.
A benign, small, papular or nodular skin neoplasm that usually arises above the upper lip. It is characterized by an epithelial proliferation with a central cavity. The cavity wall is lined with keratinocytes.
A cutaneous adnexal neoplasm with variable clinical presentation. It tends to be located in the head and neck and the presentation is papulonodular, scaly, asymptomatic, measuring up to 1-2cm, simulating a basal cell carcinoma.
The clinical characteristics of Birt-Hogg-Dubé syndrome (BHDS) include cutaneous manifestations (fibrofolliculomas, trichodiscomas/angiofibromas, perifollicular fibromas, and acrochordons), pulmonary cysts/history of pneumothorax, and various types of renal tumors. Disease severity can vary significantly even within the same family. Skin lesions typically appear during the third and fourth decades of life and typically increase in size and number with age. Lung cysts are mostly bilateral and multifocal; most individuals are asymptomatic but at high risk for spontaneous pneumothorax. Individuals with BHDS are at a sevenfold increased risk for renal tumors that are typically bilateral and multifocal and usually slow growing; median age of tumor diagnosis is 48 years. The most common renal tumors are a hybrid of oncocytoma and chromophobe histologic cell types (so-called oncocytic hybrid tumor) and chromophobe histologic cell types. Some families have renal tumor and/or autosomal dominant spontaneous pneumothorax without cutaneous manifestations.
A rare, pilar-associated mesenchyme neoplasm with follicular differentiation. It usually occurs in the face, neck, and chest. It presents as a dome-shaped papular lesion. It is composed of epithelial and mesenchymal cells. Patients with Birt-Hogg-Dube syndrome may develop follicular fibromas.
A variant of basal cell carcinoma presenting as an elevated or erythematous nodular lesion usually in the back. Morphologically, it is characterized by the presence of cords of basaloid cells extending from the epidermis into the dermis, creating a fenestrating pattern. It follows an indolent course.
A rare, benign, slow-growing and painless neoplasm of sweat glands. It usually arises in the head and neck. It is characterized by the presence of a mesenchymal chondroid stroma, fibrosis, and epithelial structures.
A low grade adenocarcinoma with ductal differentiation, arising from the sweat glands. It presents as a scar usually in the face. It is characterized by the formation of small ducts and it frequently involves nerves and perineural spaces.
A form of melanoma occurring most often on the plantar, palmar, subungual, and periungual skin. It presents as a pigmented macular lesion with irregular borders. Morphologically, it consists of atypical spindled and dendritic melanocytes. The epidermis is often hyperplastic and there is pagetoid infiltration of the epidermis by anaplastic cells.
A benign, intermediate, or malignant neoplasm that arises from the dermis.
A keratotic cutaneous polyp containing abundant connective tissue
A benign, intermediate, or malignant mesenchymal neoplasm composed of fibrohistiocytic cells, spindle fibroblastic cells, and histiocytes, in a storiform pattern.
An intermediate cutaneous mesenchymal neoplasm of uncertain differentiation, usually affecting the actinic-damaged skin of the elderly. The tumor presents as a single cutaneous nodule which is often ulcerated. Microscopically, it is characterized by the presence of highly atypical cytologic features, pleomorphism and abundant mitotic figures. The vast majority of patients have an excellent prognosis following conservative therapy. Recurrences are infrequent, and metastasis is rare.
A papillary or cauliflower-like growth characterized by the presence of foamy histiocytes within the elongated dermal papillae forms.
A very rare intraneural mass in a large nerve characterized by the interposition of mature skeletal muscle fibers and nerve fibers.
A neurofibroma that grows along small branches of nerves in the dermis in patients with neurofibromatosis. It presents as a solid cutaneous tumor.
A benign smooth muscle neoplasm arising from the arrector pili muscle, tunica media of blood vessels, and dartos muscle of the genitalia. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A cutaneous leiomyoma arising from the dartos muscle of the scrotum or labia majora.
An aggressive malignant smooth muscle neoplasm, arising from the skin. It is characterized by a proliferation of neoplastic spindle cells.
A rare congenital but non-hereditary disorder characterized by angiomas or arteriovenous malformations of the spinal cord. Clinical signs include sudden onset of radicular pain localizable to a dermatome with overlying cutaneous vascular lesions. Untreated, the clinical course follows a progression of sensory loss, weakness to paralysis and incontinence. However, clinical prognosis improves with endovascular embolization and/or surgical excision of the spinal lesion.
A hemangioma present at birth. It is characterized by the presence of rubbery skin lesions.
Tufted angioma is a rare benign vascular lesion that predominantly affects children under 5 years of age but may occur in adulthood. Some cases of tufted angioma have been reported in the mother during pregnancy, whereas in other cases the tufted angioma may be congenital. The lesions occur predominantly on the neck, shoulders, and trunk and appear histologically in a 'cannonball' distribution of rounded nodules or tufts of capillary-sized vessels in the dermis, with lymphatic vessels present at the periphery. The natural history is slow progressive growth, after which it tends to remain stable in size. Regression has been reported in some cases. Tufted angioma should be distinguished from kaposiform hemangioendothelioma (KHE). Multiple tufted angioma and KHE may be associated with Kasabach-Merritt syndrome (141000), which is characterized by severe thrombocytopenia and consumption of coagulation factors (summary by Tille et al., 2003).
A hemangioma characterized by the presence of hobnail endothelial cells.
A malignant vascular neoplasm arising from the skin.
A malignant vascular neoplasm of the skin arising from the lymphatic vessels.
A glomus tumor arising from the skin. It usually presents as a small red-blue nodule and it often associated with pain at the site.
A benign or malignant hemangiopericytoma arising in the skin.
A malignant hemangiopericytoma arising in the skin.
A vascular proliferation arising from the skin. It is characterized by the presence of prominent endothelial cells and formation of vascular channels.
An intermediate, rarely metastasizing blood vessel neoplasm. It is characterized by the presence of lymphatic-like vascular channels and papillary endothelial proliferation.
A benign melanocytic nevus characterized by the presence of desmoplastic stroma.
A tan, regularly bordered patch with darker macules within the lesion.
Bazex syndrome is an X-linked dominant disorder characterized by a triad of congenital hypotrichosis, follicular atrophoderma affecting the dorsa of the hands and feet, the face, and extensor surfaces of the elbows or knees, and the development of basal cell neoplasms, including basal cell nevi and basal cell carcinomas from the second decade onward (Yung and Newton-Bishop, 2005). Rombo syndrome (180730) has similar features, but shows autosomal dominant inheritance.
A Malignant mesothelioma originating from cells of the peritoneum (the thin layer of mesothelium lining the abdomen). Peritoneal mesothelioma is the second most common form of mesothelioma after pleural mesothelioma.
A rare malignant mesothelioma that arises from the pericardium. Clinical presentation includes pericardial effusion, congestive heart failure, a mass or cardiac tamponade. Surgical resection is the treatment of choice. Adjunct treatments of chemotherapy or radiation have not improved outcomes. The prognosis is extremely poor due to its late presentation and difficulty obtaining complete surgical excision. In most cases the diagnosis is made at autopsy or postoperatively.
A rare benign neoplasm that arises from the mesothelial cells of the pleura. It is characterized by a proliferation of epithelioid cells forming glandular and tubular patterns in a fibrous stroma.
A rare, benign neoplasm that arises from the peritoneum and is characterized by the presence of gland like structures. Cytologic atypia is absent.
A malignant mesenchymal neoplasm arising from adipocytes.
A benign mesenchymal neoplasm composed of adipose (fatty) tissue. The most common representative of this category is the lipoma.
An infiltrating ductal breast carcinoma associated with stromal fibrosis.
Breast carcinoma that has developed in relatives of patients with history of breast carcinoma.
A phyllodes tumor of the breast characterized by infiltrative margins and a sarcomatous stromal component. The sarcomatous stroma usually displays features of fibrosarcoma. Liposarcomatous, osteosarcomatous, or rhabdomyosarcomatous elements may also be present.
A non-metastasizing neoplasm arising from the breast parenchyma.
A breast fibroadenoma characterized by a very large size. This term has also been used as a synonym for juvenile fibroadenoma by some authors. The latter is characterized by epithelial hyperplasia and an increased stromal cellularity.
A breast fibroadenoma characterized by epithelial hyperplasia and an increased stromal cellularity.
An endometrioid adenocarcinoma arising from the ovary. It comprises 10% to 25% of all primary ovarian carcinomas. Grossly, endometrioid carcinoma may present as a cystic or solid mass. Microscopically, the tumor greatly resembles the appearance of the ordinary type of endometrial adenocarcinoma. As a group, endometrioid carcinoma has a prognosis twice as good as that of serous or mucinous carcinoma.
A benign, borderline, or malignant epithelial tumor of the ovary that is characterized by a predominance of clear and hobnail cells.
A benign, borderline, or malignant mixed epithelial tumor of the ovary. It is characterized by the presence of more than one epithelial cell type, most often serous and endocervical-type mucinous.
An aggressive carcinoma arising from the ovary. Most patients present with advanced disease. Microscopically, it is characterized by significant cytologic atypia, increased mitotic activity, and necrosis. The prognosis is usually poor.
A non-metastasizing tumor that originates from the surface epithelium of the ovary. It is composed of epithelial cells and stroma. Representative examples include serous cystadenoma, mucinous cystadenoma, clear cell adenofibroma, and benign Brenner tumor.
A benign ovarian surface epithelial-stromal tumor characterized by the presence of cystic structures lined by serous epithelial cells, mucinous columnar epithelial cells, or endometrial-type well-differentiated cells.
A benign, usually bilateral neoplasm of the ovary characterized by the presence of cystic structures that contain watery fluid and are lined by serous epithelial cells. Signs and symptoms include abdominal enlargement, pain, and vaginal bleeding.
A benign neoplasm of the ovary characterized by the presence of cystic structures lined by mucinous columnar epithelial cells.
An aggressive granulosa cell tumor that arises from the ovary and metastasizes to other anatomic sites.
A rare neoplasm arising from the ovary. Although it may occur at any age, it is more often seen in young females. Morphologically, it is characterized by a mixture of two cellular populations: well differentiated Sertoli cells and granulosa cells, with the latter constituting at least ten percent of the neoplasm. The vast majority of cases are stage I lesions at presentation and produce either estrogenic or androgenic manifestations. Although it may present as a massive ovarian tumor, it usually follows a benign clinical course. Very rare case reports of testicular lesions morphologically resembling gynandroblastomas are in fact variants of juvenile granulose cell tumor, or Sertoli cell tumor, or a combination of both.
A benign Leydig cell tumor which arises in the hilar area of the ovary.
Ovarian germ cell cancers are malignancies that arise from germ cells of the embryonic gonad. Although benign germ cell tumors are relatively common, accounting for approximately 20% of all ovarian neoplasms, malignant ovarian germ cell tumors are rare. Weiss et al. (1977) estimated that less than 5% of ovarian cancers are of germ cell origin.
A choriocarcinoma arising from the ovary. When it appears before puberty is of germ cell origin. In children and young adults signs and symptoms include precocious pseudopuberty and vaginal bleeding. Serum human chorionic gonadotropin is elevated. Germ cell derived ovarian choriocarcinoma should be differentiated from primary or metastatic gestational choriocarcinoma affecting the ovary. The prognosis of germ cell derived choriocarcinoma is less favorable and requires more aggressive chemotherapy treatment regimens compared to gestational choriocarcinoma.
A malignant germ cell tumor arising from the ovary. It usually affects females in their first two decades of life. It contains variable amounts of immature embryonal tissues. Based on the amount of immature neuroepithelial component, immature teratomas are graded from 1 to 3. The stage and grade of the tumor and the grade of the metastatic tumor are the important factors that predict prognosis. The use of cisplatin-based combination chemotherapy has significantly improved the survival rates of the patients.
An embryonal carcinoma arising from the ovary. Signs and symptoms include the presence of an abdominal mass and abdominal pain.
A non-metastasizing germ cell tumor that arises from the ovary. The vast majority of cases are benign dermoid cysts.
A malignant germ cell tumor arising from the ovary. Morphologically, it is identical to seminoma and consists of a monotonous population of germ cells with abundant pale cytoplasm and uniform nuclei. The stroma invariably contains chronic inflammatory cells, mostly T-lymphocytes. It responds to chemotherapy or radiotherapy and the prognosis relates to the tumor stage.
A usually rapidly growing malignant germ cell tumor arising from the ovary. It usually occurs in children and adolescents. Signs and symptoms include abdominal pain and a large abdominal or pelvic mass. The serum alpha-fetoprotein is almost always elevated preoperatively. Morphologically, there is marked heterogeneity due to numerous patterns of differentiation coexisting in the same tumor. The most common pattern is reticular.
A non-metastasizing neoplasm that arises from the fallopian tube. Representative examples include papilloma, adenofibroma, and leiomyoma.
A rare benign neoplasm characterized by the presence of smooth muscle cells growing within the veins of the uterine corpus. The intravascular neoplasm growth occurs outside the confines of an adjacent leiomyoma.
An uncommon carcinoma arising from the cervix. It is composed of malignant glandular epithelial cells and malignant squamous epithelial cells.
Stage 0 includes: (Tis, N0, M0). Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. FIGO no longer includes stage 0. (AJCC 7th ed.)
A superficial neoplastic process involving exclusively the vaginal squamous epithelium without extension to underlying tissue. It is classified as low- or high-grade intraepithelial neoplasia.
Intraepithelial neoplasia of the vulvar squamous epithelium. There is no evidence of invasion. This category includes vulvar high grade squamous intraepithelial lesion and vulvar intraepithelial neoplasia, differentiated type.
A benign or malignant neoplasm that affects the epididymis. Representative examples include epididymal adenomatoid tumor and epididymal adenocarcinoma.
A rare type of renal cell carcinoma. It is a well-circumscribed multicystic mass without solid areas. The inner lining of the cystic structures is composed of clear cells.
The presence of an adenoma in the cortex of the kidney.
A benign tumor of the kidney, characterized by the presence of large cells with abundant eosinophilic granular cytoplasm. The majority of these tumors are discovered incidentally, during work-up of other conditions.
A hemangiopericytoma arising from the kidney.
Stage 0is includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
An exophytic and polypoid lesion attached to the ureter by a broad base or a thin stalk.
Stage 0is includes: (Tis, N0, M0); (Tis pu, N0, M0); (Tis pd, N0, M0). Tis: Carcinoma in situ. Tis pu: Carcinoma in situ, involvement of the prostatic urethra. Tis pd: Carcinoma in situ, involvement of the prostatic ducts. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
A malignant neoplasm that arises from the choroid plexus. The vast majority are carcinomas.
A pituitary tumor with subarachnoid, brain, or systemic metastasis. The diagnosis of a pituitary carcinoma requires evidence of metastatic disease, either outside the central nervous system (CNS) or as separate noncontiguous foci within the CNS.
An adenoma of the anterior lobe of the pituitary gland that produces growth hormone. The vast majority of cases are hormonally functioning and are associated with either gigantism or acromegaly.
A rare adenoma of the anterior lobe of the pituitary gland that produces thyrotropin. It is usually associated with goiter and hyperthyroidism.
Benign and malignant neoplasms which arise from or metastasize to the olfactory or first cranial nerve. Clinical features may include facial pain and impairments of taste or smell.
A glioma originating in the optic nerve or optic chiasm.
A benign tumour of meningothelial cells of the meninges that usually occurs in middle age. It is typically unilateral and there is an association with neurofibromatosis type 2. [ISBN-13:978-0199552641]
Benign and malignant neoplasms which arise from the eighth cranial nerve, also referred to as the vestibulocochlear nerve. Clinical features may include hearing loss, vertigo, tinnitus, headache and involvement of the trigeminal or facial nerves.
Abnormal malignant growth of the cells that comprise cranial nerve VIII. This can lead to difficulties with hearing and balance.
A carcinoma arising in a pre-existing pleomorphic adenoma in the lacrimal gland.
A benign, usually encapsulated neoplasm of the lacrimal gland composed of epithelial and mesenchymal cells. Pleomorphic adenomas are neoplasms that develop in the salivary glands or heterotopic salivary gland tissues. It has been suggested that myoepithelial cells play a major role in the histogenesis of these tumors. In the lacrimal gland, pleomorphic adenomas presumably develop from metaplastic myoepithelial cells. --2003
A malignant mesenchymal neoplasm with skeletal muscle differentiation that arises from the orbit.
A malignant hemangiopericytoma arising in the orbit.
A capillary hemangioma arising from the orbit.
A cavernous hemangioma arising from the orbit.
A benign or malignant hemangiopericytoma arising from the orbit.
A benign congenital tumor that affects the orbit. It is one of the most common orbital tumors. It is characterized by the presence of a cystic structure that is lined by keratinizing epithelium and contains adnexal structures. Complete surgical excision is curative.
A low-grade squamous cell carcinoma that arises from the conjunctiva. It is the most common primary malignant tumor that arises from the conjunctiva. It usually affects older white males. Excessive exposure to sunlight is a risk factor. Patients may present with a mass, red eye, or pain.
A malignant melanoma within the conjunctiva of the eye.
A benign melanocytic neoplasm that arises from the conjunctiva.
A rare squamous cell carcinoma that arises from the cornea.
A melanoma within the cornea of the eye.
A malignant neoplasm that affects the iris. This category includes primary iris melanoma and metastatic malignant neoplasms to the iris.
A uveal melanoma that arises from the iris. It is the most common primary malignant neoplasm of the iris. The majority arise in preexisting nevi.
A non-metastasizing neoplasm that arises from the iris.
A benign brown pigmented area over the iris representing proliferation of melanocyte cells in the stromal layer of the iris. An iris nevus can be flat or occasionally slightly elevated.
A malignant medulloepithelioma arising from the ciliary body of the uvea.
A rare uveal melanoma that arises from the ciliary body. Patients may present with blurred vision, visual field loss, floaters, and ocular pain. The prognosis is usually poor.
A well-circumscribed benign smooth muscle neoplasm arising from the ciliary body of the eye. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A uveal melanoma that arises from the choroid. It is the most common primary malignant intraocular tumor. It usually affects Caucasians of northern European descent. It usually remains asymptomatic for a long period. When signs and symptoms occur, they include blurred vision, visual field loss, floaters, and ocular pain. Tumor size is the most important factor that relates to prognosis.
A benign, flat or slightly elevated melanocytic lesions of the posterior uveawith clearly defined margins. Choroidal nevi tend they remain stable in size, and to display features such as overlying drusen as well as retinal pigment epithelial atrophy, hyperplasia or fibrous metaplasia.
A rare, unilateral or bilateral benign retinal neoplasm. Since there is a risk of malignant transformation to retinoblastoma, patients should be closely observed.
A primary (adrenal cortex carcinoma) or a metastatic malignant neoplasm affecting the adrenal cortex. (NCI05)
A paraganglioma that is confined to the site of origin, without metastatic potential.
A rare myeloproliferative neoplasm characterized by a clonal proliferation of eosinophilic precursors resulting in persistently increased numbers of eosinophils in the blood, marrow and peripheral tissues. Since acute eosinophilic leukemia is at best exceedingly rare, the term eosinophilic leukemia is normally used as a synonym for chronic eosinophilic leukemia. In cases in which it is impossible to prove clonality and there is no increase in blast cells, the diagnosis of ""idiopathic hypereosinophilic syndrome"" is preferred. (WHO, 2001)
A malignant vascular neoplasm arising from the spleen.
A non-metastasizing neoplasm arising from any of the organs of the thoracic cavity. Representative examples include pleural adenomatoid tumor, chest wall lipoma, mediastinal schwannoma, and lung hamartoma.
A carcinoma that arises from the base of the tongue. Representative examples include squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma.
A primary or metastatic malignant neoplasm that affects the pericardium.
A primary or metastatic malignant neoplasm that affects the myocardium.
A malignant neoplasm that affects the endocardium.
A primary or metastatic malignant neoplasm involving the small intestine, large intestine, or both. Representative examples are carcinomas, lymphomas, and sarcomas.
A primary or metastatic malignant neoplasm that affects the colon or rectum. Representative examples include carcinoma, lymphoma, and sarcoma.
A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma. -- 2003
A malignant neoplasm that arises from the epithelial cells of the exocrine pancreatic tissue.
A melanoma that arises usually from the breast skin and less often from the breast glandular tissue. Primary breast melanomas are rare.
A Kaposi sarcoma arising from the conjunctiva.
A Kaposi sarcoma arising from the cornea.
A primary or metastatic malignant neoplasm that affects the structures of the chest wall. Representative examples include lymphoma and chondrosarcoma.
Cancer that is spread throughout the body, a metastatic phenomenon.
The spread of a malignant neoplasm to the large intestine. This may be from a primary large intestine malignant neoplasm, or from a malignant neoplasm at a distant site.
The spread of a malignant neoplasm to the colon. This may be from a primary large intestine malignant neoplasm, or from a malignant neoplasm at a distant site.
The spread of a malignant neoplasm to the rectum. This may be from a primary large intestine malignant neoplasm, or from a malignant neoplasm at a distant site.
A malignant neoplasm that has spread to the pancreas from another anatomic site. Representative examples include metastatic carcinomas from the gastrointestinal tract, metastatic melanomas, and renal cell carcinomas.
The spread of a malignant neoplasm from its original site of growth to the bone marrow.
The spread of a malignant neoplasm to the peritoneum from another primary anatomic site.
A condition in which a carcinoma has spread extensively throughout the peritoneal cavity.
The spread of a malignant neoplasm to the breast. This may be from a primary breast malignant neoplasm on the opposite side, or from a malignant neoplasm at a distant site.
A malignant neoplasm that has spread to the cervix from another anatomic site.
A malignant neoplasm that has spread to the vagina from another anatomic site.
A malignant neoplasm that has spread to the vulva from another anatomic site.
The spread of a malignant neoplasm to the prostate gland from an adjacent or distant anatomic site.
A malignant neoplasm that has spread to the testis from another anatomic site.
A malignant neoplasm that has metastasized to the epididymis from another anatomic site.
A malignant neoplasm that has spread to the ureter from another anatomic site.
The spread of a malignant neoplasm to the urinary bladder wall from an adjacent or distant anatomic site.
A malignant neoplasm that has spread to the urethra from another anatomic site.
The spread of a malignant neoplasm to the nervous system. This may be from a primary nervous system malignant neoplasm, or from a malignant neoplasm at a distant site.
A malignant neoplasm metastasizing to the pituitary gland from another anatomic site. The vast majority are carcinomas usually arising from the breast, lung, and gastrointestinal tract.
A malignant neoplasm that has spread to the spinal cord from another anatomic site or system. Representative examples include carcinoma, lymphoma, and melanoma.
A malignant neoplasm that has spread to the eye from another anatomic site.
A malignant neoplasm that has spread to the orbit from another anatomic site.
A malignant neoplasm either directly extending to the thyroid gland from adjacent structures (e.g. pharynx, larynx, esophagus, cervical lymph nodes), or spreading to the thyroid gland from distant anatomic sites, most frequently kidney, lung, uterus, breast, and skin. The majority of cases are carcinomas, lymphomas, and melanomas.
Stage 0 carcinoma of the pharynx according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ: intraepithelial or invasion of lamina propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
A precancerous neoplastic intraepithelial process involving either the squamous and transitional zones of the anal canal or the perianal skin (anal margin).
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ (limited to tubal mucosa). N0: No regional lymph node metastasis. M0: No distant metastasis. FIGO no longer includes stage 0. (AJCC 7th ed.)
A precancerous neoplastic lesion that arises from the penis and is associated with human papillomavirus infection. It is characterized by the proliferation of transformed basaloid cells within the epithelium. The basaloid cells exhibit nuclear pleomorphism, hyperchromasia, and loss of polarity.
A non-metastasizing neoplasm arising from the oral cavity. Representative examples include hemangioma, tongue lipoma, and buccal mucosa papilloma.
A non-metastasizing neoplasm that arises from the upper or lower gingiva.
A non-metastasizing neoplasm that arises from the hard palate, soft palate, or uvula.
A non-metastasizing neoplasm that arises from the major or minor salivary glands. Representative examples include Warthin tumor, monomorphic adenoma, and pleomorphic adenoma.
A non-metastasizing neoplasm that arises from the sublingual gland.
A non-metastasizing neoplasm arising from the middle ear. Representative examples include middle ear polyp and adenoma.
A non-metastasizing neoplasm that arises from the nasal cavity. Representative examples include Schneiderian papilloma and salivary gland-type adenoma.
A non-metastasizing neoplasm that arises from the paranasal sinuses. Representative examples include Schneiderian papilloma and salivary gland-type adenoma.
A non-metastasizing neoplasm that arises from the oropharynx.
A non-metastasizing neoplasm that arises from the glottis.
A non-metastasizing neoplasm that arises from the supraglottis.
A non-metastasizing neoplasm that arises from the epiglottis.
A non-metastasizing neoplasm that arises from the myocardium.
A non-metastasizing neoplasm that arises from the endocardium.
A non-metastasizing neoplasm arising from the small or large intestine.
A non-metastasizing neoplasm arising from the wall of the colon and rectum.
A non-metastasizing neoplasm arising from the anus. Representative examples include squamous papilloma and papillary hidradenoma.
A non-metastasizing neoplasm arising from the pancreas.
A benign, non-metastasizing neoplasm arising from the exocrine pancreas.
A rare non-metastasizing neoplasm that arises from the sternum.
A non-metastasizing neoplasm that arises from the external, middle, or internal ear. Representative examples include ceruminous adenoma, polyp, and lipoma.
A benign papillary neoplastic growth on the skin composed of epithelial cells and a fibrous stalk. It usually develops in the eyelid, axilla, neck, upper chest, and groin.
A non-metastasizing neoplasm that arises from the hair follicles, sebaceous glands, or sweat glands. Representative examples include cylindroma, hidrocystoma, hidradenoma, and sebaceoma.
A benign adipose tissue neoplasm of the skin.
A benign vascular neoplasm that arises in the skin.
Fatty tumors on the eyelids. [ORCID:0000-0003-0986-4123]
A benign adipose tissue neoplasm of the external ear.
A benign adipose tissue neoplasm of the axilla.
A benign adipose tissue neoplasm of the spinal cord. It is usually associated with dysraphism in which the intraspinal component communicates with a subcutaneous lipoma through a defect in the posterior elements of the spine. Non-dysraphic intramedullary spinal cord lipomas are very rare.
A non-metastasizing neoplasm that arises from the connective and soft tissue. Representative examples include lipoma, leiomyoma, fibroma, and osteoma.
A non-metastasizing neoplasm that arises from the breast parenchyma in males.
A polyp that arises from the surface of the cervix.
A non-metastasizing neoplasm that arises from the Bartholin gland. Representative examples include adenoma and adenomyoma.
A meningioma that affects the spinal cord.
A non-metastasizing, functioning or non-functioning neoplasm that arises from an endocrine organ. Representative examples include thyroid gland follicular adenoma and parathyroid gland adenoma.
A hole (perforation) in the wall of the colon.
A jugulotympanic paraganglioma that metastasizes to other anatomic sites.
An abnormal enlargement or swelling in the pelvic region.
Viral infections of the brain, spinal cord, meninges, or perimeningeal spaces.
An infection that is caused by the organism Hemophilus influenza.
A primary or metastatic malignant neoplasm involving the brain or spinal cord. Representative examples include anaplastic astrocytoma, glioblastoma, anaplastic (malignant) meningioma, lymphoma, and metastatic carcinoma from another anatomic site.
A primary or metastatic malignant tumor occurring in the meninges, which surround the brain and spinal cord. The most common are meningiomas. - 2004
A benign tumor occurring in the meninges, which surround the brain and spinal cord. The most common are meningiomas. - 2004
Persistent inflammation of the superficial portion of the gastric mucosa. It is a condition that predisposes to the development of ulcer and mucosa-associated lymphoid tissue lymphoma.
An anxiety disorder characterized by an intense, irrational fear of an object, activity, or situation. The individual seeks to avoid the object, activity, or situation. In adults, the individual recognizes that the fear is excessive or unreasonable.
Insomnia as a result of an extrinsic cause.
A type of apraxia that is characterized by difficulty or inability to execute speech movements because of problems with coordination and motor problems, leading to incorrect articulation. An increase of errors with increasing word and phrase length may occur.
Shunting of blood flow from the arterial to the venous side of a hemodialysis access.
Squamous or glandular cervical intraepithelial neoplasia characterized by the presence of mild dysplastic changes.
Cervical squamous intraepithelial neoplasia characterized by the presence of maturation in the upper half of the squamous epithelium and conspicuous nuclear atypia which is present in all epithelial layers. Mitotic figures are present in the basal two thirds of the epithelium.
A psychotic syndrome caused by damage to the brain by lack of thiamine (vitamin B1). Signs and symptoms include anterograde and retrograde amnesia, confabulation, apathy, ataxia, and coma.
A condition characterized by a temporary imbalance between the oxygen supply and demand of the heart muscle in the newborn.
Aspiration of meconium, blood, amniotic fluid or gastric contents around the time of delivery resulting in clinical symptoms from airway obstruction, parenchymal injury, and ventilation-perfusion mismatch. This may lead to persistent pulmonary hypertension in the newborn.
Inhalation of fluid from the amniotic sac into the lungs by the neonate.
An enlargement of the thyroid gland with congenital onset.
Reduced concentration of thyroid hormone(s), usually associated with a non-thyroidal illness, that resolves spontaneously.
A benign hamartomatous tumor that possesses various epidermal derivatives and is due to sequestration of skin along the lines of embryonic closure.
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
A benign neoplasm arising from the dermis. It is characterized by the presence of neoplastic fibroblasts without malignant characteristics.
A benign or malignant neoplasm arising from the dermis. It is characterized by the presence of neoplastic fibroblasts.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the stomach. The vast majority of cases arise from the corpus-fundus region. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent. It may be associated with autoimmune chronic atrophic gastritis, multiple endocrine neoplasia type 1, or it may be sporadic.
An invasive adenocarcinoma confined to the mucosa or mucosa and submucosa of the gastric wall. The regional lymph nodes may or may not be involved. It usually occurs in the lesser curvature. The 5-year survival rate following resection is between 80 percent and 95 percent, and remains high even when lymph node metastases are present.
Llymphoma that originates in the stomach itself.
A carcinoma arising in the anal margin or perianal skin (below the anal verge and involving the perianal hair-bearing skin). It includes basal cell and squamous cell carcinoma. Anal margin carcinoma is staged as a skin carcinoma, separately from anal canal carcinoma. -- 2003
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the small or large intestine. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the small intestine. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A melanoma arising from the anus. Clinical presentation includes rectal bleeding, tenesmus, pain, and change in bowel habit. The prognosis is usually poor.
An aggressive malignant melanocytic neoplasm that arises from the rectum.
A low or high grade astrocytoma that arises in the spinal cord.
A WHO grade IV malignant astrocytic tumor that arises from the brain, usually the cerebral hemispheres. It is characterized by the presence of poorly differentiated astrocytes, cellular polymorphism, nuclear atypia, and increased mitotic activity. The prognosis is poor.
A rare squamous cell carcinoma that arises from the scrotum. It has been associated with exposure to environmental and industrial carcinogens. The prognosis depends on the extent of lymph node involvement.
Vaginal intraepithelial neoplasia characterized by the presence of koilocytosis and disorganization and thickening of the basal layer.
Vaginal intraepithelial neoplasia characterized by the presence of nuclear intraepithelial neoplastic changes in the lower two-thirds of the epithelium and parakeratosis.
A rare, highly malignant epithelial tumor that develops from a hydatidiform mole (50%), following abortion (25%), or during normal pregnancy (22%). It is characterized by the presence of invasive and anaplastic trophoblastic tissue composed of intermediate trophoblastic cells, cytotrophoblasts and syncytiotrophoblasts, abundant vascularity, and secretion of human chorionic gonadotropin. Because of rapid growth and a high propensity for hemorrhage, this neoplasm often constitutes a medical emergency.
A cancer arising in a cell of the Bartholin gland, a racemose gland located slightly posterior to the opening of the vagina.
A benign, mesenchymal neoplasm that arises from the breast. It is surrounded by a thin capsule and composed of mature adipose tissue cells. Atypia is absent.
A carcinoma derived from a squamous epithelial cell of the tongue.
A squamous cell carcinoma that arises from the hard or soft palate.
A benign, slow-growing tumor that arises from the parotid gland. It is composed of cells that demonstrate both epithelial and mesenchymal differentiation. It is the most common neoplasm of salivary gland origin and women are more often affected than men.
A benign or malignant neoplasm that affects the pericardium.
A benign or malignant neoplasm that affects the external ear. Representative examples include ceruminous adenoma, polyp, and carcinoma.
A malignant neoplasm that affects the external ear. Representative examples include squamous cell carcinoma, basal cell carcinoma, and ceruminous adenocarcinoma.
A non-metastasizing neoplasm that arises from the external ear. Representative examples include ceruminous adenoma, polyp, and lipoma.
A benign form of endometrial hyperplasia with crowded endometrial glands and little stroma between the glands. Complex hyperplasia has low risk of progression to endometrial carcinoma.
A benign form of endometrial hyperplasia with increased number of cells with atypia. The atypical cells are large and irregular and have an increased nuclear/cytoplasmic ratio. The risk of progression to endometrial carcinoma rises with the increasing degree of cell atypia.
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to ""short stature"" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
A meningioma that arises within the cranial cavity.
A congenital or acquired cyst that is present in the central nervous system.
An intraepithelial carcinoma of the middle ear without evidence of invasion.
A WHO Grade 1 astrocytoma which arises in the cerebellum. The tumor is composed of spindle shaped cells with numerous collections of reddish astrocytic fibers called Rosenthal fibers. Over 80% or the cerebellar astrocytomas of childhood are pilocytic. Pilocytic astrocytomas may rarely occur in adults. They are usually treated by surgical resection and in most cases have a favorable prognosis.
A germ cell tumor that arises in the pineal region. Representative examples include teratoma, germinoma, and choriocarcinoma.
A solitary fibrous tumor/hemangiopericytoma that arises from the meninges.
A benign or malignant, circumscribed or diffuse neoplasm that arises from melanocytes in the leptomeninges. It includes diffuse melanocytosis, leptomeningeal melanoma, and melanocytoma.
Transformation of chronic lymphocytic leukemia into aggressive non-Hodgkin lymphoma, usually diffuse large B-cell lymphoma (immunoblastic or centroblastic variant). Occasional cases of transformation to Hodgkin lymphoma have also been described, particularly in patients treated with purine nucleotide analogues. Molecular genetic studies suggest that in approximately half of the cases, the lymphoma is clonally related to the underlying chronic lymphocytic leukemia, whereas in the remaining cases the lymphoma probably represents a secondary, unrelated neoplasm.
A B-cell non-Hodgkin lymphoma composed of small lymphocytes which surround and replace the splenic white pulp germinal centers. It involves the spleen and splenic hilar lymph nodes, bone marrow, and often the peripheral blood. When lymphoma cells are present in the peripheral blood, they are usually, but not always, characterized by the presence of short polar villi. (WHO)
An indolent chronic B-cell leukemia resembling classic hairy cell leukemia but shows variant cytologic, hematologic, and immunophenotypic features and is resistant to the conventional therapy applied to hairy cell leukemia. Biologically, it is not related to hairy cell leukemia.
A type of ALL characterized by elevated levels of B-cell lymphoblasts in the bone marrow and the blood.
Juvenile myelomonocytic leukemia is an aggressive pediatric myelodysplastic syndrome (MDS)/myeloproliferative disorder (MPD) characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny (Loh et al., 2009). JMML constitutes approximately 30% of childhood cases of myelodysplastic syndrome and 2% of leukemia (Hasle et al., 1999). Although JMML is a progressive and often rapidly fatal disease without hematopoietic stem cell transplantation (HSCT), some patients have been shown to have a prolonged and stable clinical course without HSCT (Niemeyer et al., 1997). Chronic myelomonocytic leukemia (CMML) is a similar disorder with later onset. Both JMML and CMML have a high frequency of mutations affecting the RAS signaling pathway and show hypersensitivity to stimulation with GM-CSF, which causes STAT5 (601511) hyperphosphorylation (Loh et al., 2009). Genetic Heterogeneity of Juvenile Myelomonocytic Leukemia In up to 60% of cases of JMML, the RAS/MAPK pathway is deregulated due to somatic mutations in the PTPN11 (176876), KRAS (190070), and NRAS (164790) genes. Additionally, both germline and somatic mutations in the CBL gene have been found in patients with JMML, indicating a frequency of 10 to 15% of JMML patients overall (Loh et al., 2009). Somatic disruptions of the GRAF gene (ARHGAP26; 605370) have also been found in patients with JMML. About 10 to 15% of JMML cases arise in children with neurofibromatosis type I (NF1; 162200) due to germline mutations in the NF1 gene (613113). In addition, patients with Noonan syndrome (NS1, 163950; NS3, 609942) or Noonan syndrome-like disorder (NSLL; 613563) due to germline mutations in the PTPN11, KRAS2, and CBL genes, respectively, also have an increased risk of developing JMML. Genetic Heterogeneity of Chronic Myelomonocytic Leukemia Somatic mutations in the CBL, ASXL1 (612990), TET2 (612839), and SF3B1 (605590) genes have been found in patients with CMML.
A lymphoma that arises from the testis and is not associated with lymphoma in another anatomic site.
Lymphangiomyomatosis involving the lungs and local lymph nodes. Patients usually present with chylous pleural effusion. The clinical course is variable. Patients with resectable lesions usually have a favorable clinical outcome. Patients with diffuse lesions usually have a progressive clinical course.
PMM2-CDG (CDG-Ia) (previously known as congenital disorder of glycosylation type 1a), the most common of a group of disorders of abnormal glycosylation of N-linked oligosaccharides, is divided into three types: infantile multisystem, late-infantile and childhood ataxia-intellectual disability, and adult stable disability. The three types notwithstanding, clinical presentation and course are highly variable, ranging from infants who die in the first year of life to mildly involved adults. Clinical presentations tend to be similar in sibs. In the infantile multisystem type, infants show axial hypotonia, hyporeflexia, esotropia, and developmental delay. Feeding problems, vomiting, failure to thrive, and impaired growth are frequently seen. Subcutaneous fat may be excessive over the buttocks and suprapubic region. Two distinct clinical presentations are observed: (1) a non-fatal neurologic form with strabismus, psychomotor retardation, and cerebellar hypoplasia in infancy followed by neuropathy and retinitis pigmentosa in the first or second decade and (2) a neurologic-multivisceral form with approximately 20% mortality in the first year of life. The late-infantile and childhood ataxia-intellectual disability type, with onset between age three and ten years, is characterized by hypotonia, ataxia, severely delayed language and motor development, inability to walk, and IQ of 40 to 70; other findings include seizures, stroke-like episodes or transient unilateral loss of function, retinitis pigmentosa, joint contractures, and skeletal deformities. In the adult stable disability type, intellectual ability is stable; peripheral neuropathy is variable, thoracic and spinal deformities progress, and premature aging is observed; females lack secondary sexual development and males may exhibit decreased testicular volume. Hyperglycemia-induced growth hormone release, hyperprolactinemia, insulin resistance, and coagulopathy may occur. An increased risk for deep venous thrombosis is present.
Congenital disorders of glycosylation (CDGs) are divided into 2 main groups: type I CDGs (see, e.g., 212065) comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, whereas type II CDGs (see, e.g., 212066) refer to defects in the trimming and processing of the protein-bound glycans either late in the endoplasmic reticulum or the Golgi compartments. Conventionally, untyped and unclassified cases are labeled 'CDG-x' (Orlean, 2000; Marquardt and Denecke, 2003). The phenotypes described in this entry most likely do not represent a single disorder, but have been referred by the authors as CDG-x and are included here pending further molecular characterization. In a review of CDGs, Marquardt and Denecke (2003) stated that more than 20% of CDG patients identified still cannot be ascribed to a known enzyme defect and are thus named CDG-x.
A poorly differentiated squamous cell carcinoma characterized by the presence of malignant cells with spindle cell features.
A benign hair follicle neoplasm with trichoblastic differentiation. It usually presents as a solitary papular lesion It most often presents on the head and neck area, but it may develop in any anatomic site containing hair follicles. Because of its benign nature, treatment usually is not required, provided that the diagnosis has been established with certainty.
An extragonadal malignant teratoma that arises from the mediastinum. It is characterized by the presence of embryonic or fetal tissues.
A malignant mesenchymal cell neoplasm that affects the urinary bladder.
A malignant mesenchymal neoplasm that arises from the breast. Representative examples include angiosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, and extraskeletal osteosarcoma.
A sex cord-stromal tumor that arises from the testis and is characterized by the presence of neoplastic cells with features of Sertoli cells. It usually presents as a slow growing testicular mass. The vast majority of cases follow a benign clinical course.
A usually aggressive invasive adenocarcinoma of the prostate gland composed of large glands containing tall columnar cells. The columnar cells have abundant cytoplasm and are reminiscent of endometrial carcinoma. This type of adenocarcinoma has a tendency to metastasize to the lung and penis.
Acute Promyelocytic leukemia characterized by the presence of hypergranular promyelocytes and characteristic cells that contain bundles of Auer rods.
An acute leukemia of ambiguous lineage in which there is a dual population of blasts with each population expressing markers of a distinct lineage (myeloid and lymphoid or B-and T-lymphocyte). (WHO, 2001) -- 2003
Replacement of corneal tissue with scar tissue as a result of injury to the deeper layers of the cornea.
Anomaly in the level or the function of hemoglobin, the oxygen-carrying protein of erythrocytes.
An infectious process affecting the ovary.
An overwhelming, irrational, and persistent fear of taking and failing tests.
Narrowing of the lumen of an arteriovenous graft.
Partial or complete occlusion of the lumen of an arteriovenous graft by a thrombus.
A bulge in a weakened wall segment of an arteriovenous graft.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) – previously referred to as arrhythmogenic right ventricular dysplasia (ARVD) – is characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia and sudden death in young individuals and athletes. It primarily affects the right ventricle, and it may also involve the left ventricle. The presentation of disease is highly variable even within families, and some affected individuals may not meet established clinical criteria. The mean age at diagnosis is 31 years (±13; range: 4-64 years).
The fumarate salt form of metoprolol, a cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties and devoid of intrinsic sympathomimetic activity. Metoprolol antagonizes beta 1-adrenergic receptors in the myocardium, thereby reducing the rate and force of myocardial contraction, and consequently a diminished cardiac output. This agent may also reduce the secretion of renin with subsequent reduction in levels of angiotensin II thereby preventing vasoconstriction and aldosterone secretion.
The hydrobromide salt form of dextromethorphan, a synthetic, methylated dextrorotary analogue of levorphanol, a substance related to codeine and a non-opioid derivate of morphine. Dextromethorphan exhibits antitussive activity and is devoid of analgesic or addictive property. This agent crosses the blood-brain-barrier and activates sigma opioid receptors on the cough center in the central nervous system, thereby suppressing the cough reflex.
An orally bioavailable sulfonamide urea derivative with antihyperglycemic activity. Upon administration, glibornuride binds to and blocks the sulfonylurea receptor type 1 (SUR1) subunit of the ATP-sensitive inwardly-rectifying potassium (K(ATP)) channels on the membranes of pancreatic beta cells. This prevents the inward flow of positively charged potassium (K+) ions into the cell, and induces a calcium ion (Ca2+) influx through voltage-sensitive calcium channels, which triggers exocytosis of insulin-containing granules. Insulin stimulates glycogen synthesis and inhibits gluconeogenesis, which together lower blood glucose levels.
A sulfapyrimidine derivative,also known as glycodiazine, with antihyperglycemic activity. Like sulfonylureas, glymidine is able to lower blood glucose levels by increasing the release of insulin from pancreatic beta cells and increasing the sensitivity of peripheral tissues to insulin.
The butyrate salt form of hydrocortisone, a synthetic glucocorticoid receptor agonist with antiinflammatory, antipruritic and vasoconstrictive effects. Binding and activation of the glucocorticoid receptor results in the activation of lipocortin that in turn inhibits cytosolic phospholipase A2. Lack of phospholipase A2 prevents the release of arachidonic acid, precursor for inflammatory mediator prostaglandins and leukotrienes, from the cell membrane. Secondly, mitogen-activated protein kinase (MAPK) phosphatase 1 is induced, thereby leading to dephosphorylation and inactivation of Jun N-terminal kinase directly inhibiting c-Jun mediated transcription. Finally, transcriptional activity of nuclear factor (NF)-kappa-B is blocked, thereby inhibits the transcription of cyclooxygenase 2, which is essential for prostaglandin production.
The hydrochloride salt of a synthetic piperidine ester with opioid analgesic activity. Meperidine mimics the actions of endogenous neuropeptides via opioid receptors such as the mu-opioid receptor, thereby producing characteristic morphine-like effects including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia and physical dependence.
The sodium salt form of danaparoid, a synthetic low molecular weight heparin (LMWH) derived from porcine gut mucosa with anticoagulant activity. Danaparoid sodium binds to antithrombin III and inhibits the activity of activated factor X (factor Xa) and, to a lesser extent, activated factor II (thrombin) thereby preventing fibrin formation. Compared to heparin, danaparoid sodium exhibits a much higher ratio of anti-factor Xa activity to anti-factor IIa activity (22:1).
The benzoate ester of metronidazole, a synthetic nitroimidazole derivative with antiprotozoal and antibacterial activities.
Solutions prepared for peritoneal dialysis for exchange of solutes below a certain molecular size (determined by the cutoff threshold of the membrane material) across a semipermeable membrane (i.e., the peritoneum). The threshold of the peritoneum differs from patient to patient.
The sodium salt form of olsalazine with anti-inflammatory activity. Olsalazine sodium is bioconverted to 5-aminosalicylic acid (5-ASA) in the colon by colonic bacteria. 5-ASA has anti-inflammatory activity in ulcerative colitis.
The husk of the dried ripe seeds of the Plantago psyllium, P. Indica, P. Ovata, and P. Arenaria plants with laxative and cholesterol lowering activities. The husks contain mucilage that swells on exposure to water and provides an indigestible mucilaginous mass in the intestines, thereby causing lubrication, contraction of the smooth muscles of the intestinal walls, and thus stimulating bowel movement. Psyllium husk is rich in soluble fiber and has a cholesterol-lowering effect.
Any agent belonging to the class of loop diuretics. Loop diuretics block and inhibit the function of the sodium-potassium-chloride (Na+, K+, Cl-) cotransporter system in the thick ascending limb of the loop of Henle, thereby inhibiting the reabsorption of sodium, potassium, and chloride ions. This leads to an increase in the excretion of sodium, potassium, chloride, calcium, magnesium, ammonium and water.
The besylate salt of amlodipine, a synthetic dihydropyridine with antihypertensive and antianginal effects. Amlodipine inhibits the influx of extracellular calcium ions into myocardial and peripheral vascular smooth muscle cells, thereby preventing vascular and myocardial contraction. This results in a dilatation of the main coronary and systemic arteries, decreased myocardial contractility, increased blood flow and oxygen delivery to the myocardial tissue, and decreased total peripheral resistance. This agent may also modulate multi-drug response (MDR) activity through inhibition of the p-glycoprotein efflux pump.
The sodium salt form of epoprostenol, a synthetic prostacyclin, a member of the family of prostaglandins, with vasodilatory and anticoagulant activity. Epoprostenol sodium directly simulates prostaglandin receptors in arterial vascular smooth muscle, thereby causing vasodilatation. This agent also inhibits platelet aggregation by antagonizing platelet glycoprotein (GP) IIb/IIIa receptors, thereby preventing thrombus formation.
The sodium salt of a low molecular weight heparin (LMWH), obtained by controlled enzymatic depolymerization of heparin from porcine intestinal mucosa, with antithrombotic properties. Tinzaparin is a potent inhibitor of several activated coagulation factors, especially Factors Xa and IIa (thrombin); its primary activity is mediated through the plasma protease inhibitor antithrombin. In addition, this agent may inhibit angiogenesis through: 1) competitive binding of the heparin-binding sites on endothelial cells for the proangiogenic cytokines vascular endothelial growth factor (VEGF) and beta-fibroblast growth factor (beta-FGF) and 2) increasing the release of tissue factor pathway inhibitor (TFPI), a negative regulator of angiogenesis.
A hydrochloride salt form of colestipol, a positively charged, non-digestible, triamine and epoxypropane copolymer anion-exchange resin that binds to bile acids in the intestine to form an insoluble complex, which is excreted in the feces.
The hydrochloride salt of a synthetic methyl-piperidine derivative with antihistaminic and anti-serotoninergic properties. Cyproheptadine competes with free histamine (HA) for binding at HA-receptor sites, thereby competitively antagonizing histamine stimulation of HA-receptors in the gastrointestinal tract, large blood vessels, and bronchial smooth muscle. This agent also competes with free serotonin for binding at serotonin receptor sites. Cyproheptadine exhibits anticholinergic and sedative properties and has been shown to stimulate appetite and weight gain. (NCI04)
The hydrochloride salt form of chlorpromazine, a phenothiazine and traditional antipsychotic agent with anti-emetic activity. Chlorpromazine hydrochloride exerts its antipsychotic effect by blocking postsynaptic dopamine receptors in cortical and limbic areas of the brain, thereby preventing the excess of dopamine in the brain. This leads to a reduction in psychotic symptoms, such as hallucinations and delusions. Chlorpromazine hydrochloride appears to exert its anti-emetic activity by blocking the dopamine receptors in the chemical trigger zone (CTZ) in the brain, thereby relieving nausea and vomiting.
A synthetic opioid analgesic. Dihydrocodeine bitartrate mimics the actions of the endogenous opioid peptides due to its agonistic effects on the opioid receptors. Stimulation of the mu receptors produces the typical narcotic effects of analgesia, miosis, euphoria, respiratory depression, sedation, physical dependence and bradycardia. Dihydrocodeine bitartrate is twice as potent as codeine and has one third of the potency of morphine. This analgesic is used for the relief of moderate to moderately severe pain.
The hydrochloride salt form of pentazocine, a benzomorphan narcotic agonist-antagonist. Pentazocine hydrochloride binds to and activates kappa- and sigma-opioid receptors, resulting in sedation and analgesia. In addition, this agent antagonizes the mu-receptor. Pentazocine hydrochloride partially reverses opiate-induced cardiovascular, respiratory, and behavioral depression.
The hydrochloride salt of naltrexone, a noroxymorphone derivative with competitive opioid antagonistic activity. Naltrexone and its metabolite 6-beta-naltrexol reverse the effects of opioids by binding to various opioid receptors in the central nervous system CNS), including the mu-, kappa- and gamma-opioid receptors; opioid effects of analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependence are inhibited. Naltrexone is longer-acting and more potent compared to naloxone.
Insulin derivatives and preparations that are designed to induce a rapid HYPOGLYCEMIC EFFECT.
An insulin preparation that is designed to provide immediate and long term glycemic control in a single dosage. Biphasic insulin typically contains a mixture of REGULAR INSULIN or SHORT-ACTING INSULIN combined with a LONG-ACTING INSULIN.
The disodium salt of the synthetic bisphosphonate pamidronate. Although its mechanism of action is not completely understood, pamidronate appears to adsorb to calcium phosphate crystals in bone, blocking their dissolution by inhibiting osteoclast-mediated bone resorption. This agent does not inhibit bone mineralization and formation.
The hydrochloride salt form of ritodrine, a phenethylamine derivative with tocolytic activity. Ritodrine hydrochloride binds to and activates beta-2 adrenergic receptors of myocytes in the uterine myometrium, which results in decreased intensity and frequency of uterine contraction. Specifically, ritodrine hydrochloride probably activates adenyl cyclase, thereby increasing production of cyclic adenosine monophosphate (cAMP), which in turn enhancing the efflux of calcium from vascular smooth muscle cells. A lack of intracellular calcium prevents uterine myometrial contraction. In addition, this agent may directly inactivate myosin light chain kinase, a critical enzyme necessary for the initiation of muscle contractions.
A recombinant glycosylated form of erythropoietin which stimulates the differentiation and proliferation of erythroid precursors. It is used for the treatment of ANEMIA associated with CHRONIC RENAL FAILURE in dialysis and predialysis patients.
A recombinant therapeutic agent that is chemically identical to or similar to the endogenous cytokine human erythropoietin (EPO). Produced primarily by cells of the peritubular capillary endothelium of the kidney in response to hypoxia, circulating EPO binds to EPO receptors on the surface of committed erythroid progenitors in the bone marrow resulting in their replication and maturation into functional erythrocytes.
The hydrochloride salt form of cyclopentolate, an anticholinergic drug. Administered in the eye, cyclopentolate hydrochloride blocks the acetylcholine receptor in the sphincter muscle of the iris and the ciliary muscle, thereby preventing contraction. This dilates the pupil, producing mydriasis, and prevents the eye from accommodating.
The hydrochloride salt form of oxymetazoline, an imidazole derivative with a direct acting sympathomimetic property. Oxymetazoline binds to and activates alpha-2 adrenergic receptors. Upon nasal or ocular administration, oxymetazoline constricts the arterioles in the nose and eye, resulting in decreased nasal and conjunctival congestion, respectively.
Vaccines or candidate vaccines used to prevent ANTHRAX.
A bacterial vaccine used to prevent contraction of Streptococcus pneumonia.
Any agent that relaxes skeletal muscles and reduces muscle contraction.
The hydrochloride salt form of procaine, a benzoic acid derivative with local anesthetic and antiarrhythmic properties. Procaine binds to and inhibits voltage-gated sodium channels, thereby inhibiting the ionic flux required for the initiation and conduction of impulses. In addition, this agent increases electrical excitation threshold, reduces rate of rise of action potential and slows nerve impulse propagation thereby causing loss of sensation.
Any one of the substituted benzimidazole compounds with anti-ulcer activity. A proton pump inhibitor is orally administered in the neutrally charged, inactive form and, upon entering the acidic environment of the parietal cell, gets protonated and converted into its active form. The active form will covalently and irreversibly bind to the proton pump, the H+/K+-ATPase, located on the surface of parietal cells. This leads to an inhibition of the transport of hydrogen ions, in exchange for potassium ions, into the gastric lumen and results in an inhibition of gastric acid secretion.
Synthetic compounds or mixtures to treat the pain, swelling, inflammation, pruritis and discomfort associated with hemorrhoids. A hemorrhoidal preparation contains compounds with anti-inflammatory, anti-pruritic, local anesthetic or analgesic activity.
A complex mixture consisting of allergenic proteins derived from natural sources used for allergy treatment by subcutaneous or oral/sublingual route.
QUINOLONES containing a 4-oxo (a carbonyl in the para position to the nitrogen). They inhibit the A subunit of DNA GYRASE and are used as antimicrobials. Second generation 4-quinolones are also substituted with a 1-piperazinyl group at the 7-position and a fluorine at the 6-position.
Any agent that binds to and blocks serotonin (5-HT) type 3 receptors. This group of agents is used to treat nausea, vomiting, and irritable bowel syndrome. Some of the 5-HT3 antagonists also show antipsychotic efficacy.
Any agent that increases the extracellular level of the neurotransmitter serotonin (5-HT) by inhibiting its reuptake into the presynaptic cell. Increased level in the synaptic cleft prolongs the action of 5-HT on the postsynaptic receptor. This type of agent is typically used as an antidepressant and in the treatment of anxiety disorders and some personality disorders. They are also typically effective and used in treating some cases of insomnia.
A quaternary ammonium compound that serves as a long-acting cholinesterase inhibitor with parasympathomimetic activity. When used topically, demecarium inactivates both pseudocholinesterase and acetylcholinesterase, thereby preventing acetylcholine breakdown and increasing acetylcholine activity. This causes contraction of the iris sphincter muscle (producing miosis) and the ciliary muscle (affecting the accommodation reflex). In so doing, this agent increases the outflow of the aqueous humor, thereby reducing intraocular pressure.
Natural or synthetic compounds or mixtures that are applied to body surfaces such as the skin, mouth, vagina, lips, nose, ears or the eyes. A topical preparation can act only on the specific area to which it is applied or it can be applied locally to be absorbed into the blood stream and act systemically.
A drug that is used in a cream to treat certain skin conditions and in a nasal spray to treat sinus problems caused by allergies. It is being studied as a way to treat inflammation of the skin caused by radiation therapy. Mometasone is a type of corticosteroid.
Any substance that inhibits HMG-CoA reductase, a key enzyme in cholesterol synthesis. Inhibition of HMG-CoA reductase acts to lower plasma cholesterol and lipoprotein levels.
A benign wart-like, pigmented skin lesion appearing on various parts of the body at birth or early in childhood, usually in linear groupings.
Characterised by blood glucose levels that are higher than normal but not yet high enough to be classed as diabetes. Indicates a relatively high risk for the future development of diabetes.
The determination of the amount of bioavailable testosterone present in a sample.
A 21-carbon steroid, derived from CHOLESTEROL and found in steroid hormone-producing tissues. Pregnenolone is the precursor to GONADAL STEROID HORMONES and the adrenal CORTICOSTEROIDS.
A gonococcal infection of the upper urinary tract that is rapid in onset.
A primary or metastatic malignant neoplasm involving the vulva.
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a severe or complete loss of strength, whereas hemiparesis refers to a relatively mild loss of strength.
Acute inflammation of the endocardium. Bacteria is the usual etiologic agent, and the distinction between ""acute"" and ""subacute"" has traditionally been made based on the pathogenic organism and clinical presentation.
Large or prominent malar surface of the zygomatic bone of the skull, which is convex and forms the prominence of the 'cheek bones'. [ORCID:0000-0001-5889-4463, pmid:19125436]
Complete or partial blockage of the ureter at the point where it enters the kidney that is present at birth.
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form. [HPO:sdoelken]
family of gastrointestinal peptide hormones that excite the secretion of gastric juices; may also occur in the central nervous system.
A selective aldosterone deficiency resulting from diminished RENIN-generated ANGIOTENSIN II, a key stimulus to aldosterone secretion. Previously, it was called type IV renal tubular acidosis.
Functionally related to the poppy (Papaver somniferum) alkaloid morphine, natural or synthetic Opiates have widespread effects in the central nervous system, and on smooth muscle, due to activation of specific delta, mu, and kappa opiate receptors (each controlling different brain functions). Opiates include natural ingredients of the poppy and their derivatives - opium, morphine, codeine, and heroin. Morphine preparations are used as analgesic, sedative, or anxiolytic agent, but are also abused as street drugs. (NCI04)
The sodium salt form of warfarin, a coumarin and a vitamin K antagonist, with anticoagulant activity. Warfarin sodium inhibits both vitamin K and vitamin K epoxide reductases, thereby interfering with the cyclic interconversion of vitamin K epoxide to its reduced form, vitamin KH2. Vitamin KH2 is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins. As a result, maturation of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Without these coagulation factors, thrombogenesis and blood clot formation are prevented.
A condition due to a deficiency of one or more essential vitamins. (Dorland, 27th ed)
The cessation of life due to heart abnormalities or disease.
A congenital gingival tumor that occurs along the alveolar ridge of the maxilla. It usually affects female infants. The histogenesis is unknown. Morphologically, it is characterized by the presence of large cells with eosinophilic granular cytoplasm. Complete surgical resection is curative.
The covalent chemical or post-translational biochemical addition of carbohydrate or glycosyl groups to peptides or proteins by glycosyl transferases.
A form of Creutzfeldt-Jakob disease that is most commonly contracted after consuming meat from an animal suffering from bovine spongiform encephalopathy.
A progestogen-like compound used as a cattle feed additive for its growth promoting effects and suppression of estrus (heat) in heifers. Critics have claimed that hormones used as growth promotants in cattle may cause breast cancer. (NCI)
A term used to describe the psychological aspects of PREMENSTRUAL SYNDROME, such as the ""indescribable tension"", depression, hostility, and increased seizure activity in women with seizure disorder.
A pathological condition that is characterized by a host of cranial symptoms, such as headaches, abnormal functions of the eyes and the ears, and psychological and mental disorders. This syndrome usually appears after neck injuries, inflammation, or neoplasm.
A malignant (clonal) hematologic disorder, involving hematopoietic stem cells and characterized by the presence of primitive or atypical myeloid or lymphoid cells in the bone marrow and the blood which occurs in cattle
Pathological conditions (Disorder, SYNDROME, or DISEASE) whose SIGNS AND SYMPTOMS manifest late in the life of an individual.
Drugs used by veterinarians in the treatment of animal diseases. The veterinarian's pharmacological armamentarium is the counterpart of drugs treating human diseases, with dosage and administration adjusted to the size, weight, disease, and idiosyncrasies of the species. In the United States most drugs are subject to federal regulations with special reference to the safety of drugs and residues in edible animal products.
The use of two or more chemicals simultaneously or sequentially to induce anesthesia. The drugs need not be in the same dosage form.
Agents that are used to stimulate appetite. These drugs are frequently used to treat anorexia associated with cancer and AIDS.
The process by which methyl groups are added to nucleotides in genomic DNA.
Excessive growth of the gingiva either by an increase in the size of the constituent cells (GINGIVAL HYPERTROPHY) or by an increase in their number (GINGIVAL HYPERPLASIA). (From Jablonski's Dictionary of Dentistry, 1992, p574)
The branchiooculofacial syndrome (BOFS) is characterized by: branchial (cervical or infra- or supra-auricular) skin defects that range from barely perceptible thin skin or hair patch to erythematous ""hemangiomatous"" lesions to large weeping erosions; ocular anomalies that can include microphthalmia, anophthalmia, coloboma, and nasolacrimal duct stenosis/atresia; and facial anomalies that can include ocular hypertelorism or telecanthus, broad nasal tip, upslanted palpebral fissures, cleft lip or prominent philtral pillars that give the appearance of a repaired cleft lip (formerly called ""pseudocleft lip"") with or without cleft palate, upper lip pits, and lower facial weakness (asymmetric crying face or partial 7th cranial nerve weakness). Malformed and prominent pinnae and hearing loss from inner ear and/or petrous bone anomalies are common. Intellect is usually normal.
A benign or malignant neoplasm that affects the skull base.
An autosomal dominant inherited partial epilepsy syndrome with onset between age 3 and 13 years. Seizures are characterized by PARESTHESIA and tonic or clonic activity of the lower face associated with drooling and DYSARTHRIA. In most cases, affected children are neurologically and developmentally normal. (From Epilepsia 1998 39;Suppl 4:S32-S41)
A syndrome characterized by outbreaks of late term abortions, high numbers of stillbirths and mummified or weak newborn piglets, and respiratory disease in young unweaned and weaned pigs. It is caused by PORCINE RESPIRATORY AND REPRODUCTIVE SYNDROME VIRUS. (Radostits et al., Veterinary Medicine, 8th ed, p1048)
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous glycoprotein erythropoietin (Epo). Epo promotes the differentiation and maturation of hematopoietic progenitors into erythrocytes; is a mitogen and a chemoattractant for endothelial cells; stimulates activated and differentiated B-cells and enhances B-cell immunoglobulin production and proliferation; and is hypoxia-inducible. (NCI04)
A neoplasm arising from hematopoietic cells found in the bone marrow, peripheral blood, lymph nodes and spleen (organs of the hematopoietic system). Hematopoietic cell neoplasms can also involve other anatomic sites (e.g. central nervous system, gastrointestinal tract), either by metastasis, direct tumor infiltration, or neoplastic transformation of extranodal lymphoid tissues. The commonest forms are the various types of leukemia, Hodgkin and non-Hodgkin lymphomas, myeloproliferative neoplasms, and myelodysplastic syndromes.
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue).
Infection with ROSEOLOVIRUS, the most common in humans being EXANTHEMA SUBITUM, a benign disease of infants and young children.
Infections with ASTROVIRIDAE, causing gastroenteritis in human infants, calves, lambs, and piglets.
Infections with viruses of the genus RUBULAVIRUS, family PARAMYXOVIRIDAE.
Growth hormone (somatotropin) can be synthesized with methods of recombinant DNA technology. Since action of GH is highly species-specific, recombinant growth hormones of several species (including humans, cows, and pigs) have been developed. They have been used to stimulate growth.
Glycoprotein growth factors produced by monocytes, macrophages, or activated lymphocytes that stimulate the proliferation of bone marrow cells and differentiation of stem cells into colonies of granulocytes, monocytes, or macrophages. These substances act in either paracrine or autocrine fashion on marrow cells, appear to act synergistically in complex and poorly understood ways. Each appears to exert actions on several lines of progenitor cells and to influence end cell function. Treatment with colony-stimulating factors (CSF) can help the blood-forming tissue recover from the effects of chemotherapy and radiation therapy. These factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF).
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine granulocyte colony-stimulating factor (G-CSF). Secreted by monocytes, macrophages and neutrophils and other cells after activation, G-CSF stimulates the proliferation and differentiation of hematopoietic progenitor cells committed to the neutrophil/ granulocyte lineage. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous glycoprotein cytokine growth factor granulocyte-macrophage colony stimulating factor (GM-CSF). Therapeutic GM-CSF induces the clonal expansion and differentiation of progenitor blood cells and stimulates the cytotoxicity of monocytes and neutrophils, thereby restoring immune function and host antitumor immune responses and stimulating engraftment of transplanted bone marrow tissue. (NCI04)
Any agent that prevents the human immunodeficiency virus (HIV) from reproducing.
A pharmacological agent that inhibits DNA replication or RNA synthesis.
Inhibitors of HIV INTEGRASE, an enzyme required for integration of viral DNA into cellular DNA.
Compounds which inhibit or antagonize biosynthesis or actions of integrase.
Agents that increase energy expenditure and weight loss by neural and metabolic regulation.
DNA vaccines are used in vaccination in way that differs from those are designed to be inserted into germ line of vaccines. Therefore, this is a vaccine not a therapy for modifying genetic information (gene therapy). Direct innoculation of DNA vaccine causes expression of the recombinant DNA by cells in the inoculated host. This expression of the recombinant DNA produces protein of interest that promotes antibody, cytolytic T cell and protective immune responses.
A condition characterized by the presence of ENDOTOXINS in the blood. On lysis, the outer cell wall of gram-negative bacteria enters the systemic circulation and initiates a pathophysiologic cascade of pro-inflammatory mediators.
Acute INFLAMMATION in the INTESTINAL MUCOSA of the continent ileal reservoir (or pouch) in patients who have undergone ILEOSTOMY and restorative proctocolectomy (PROCTOCOLECTOMY, RESTORATIVE).
Elevated rate of chromosomal breakage or interchanges occurring either spontaneously or following exposure to various DNA-damaging agents. This feature may be assayed by treatment of cultured lymphocytes with agents such as chemical mutagens, irradiation, and alkylating agents.
Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones.
A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
A process that results in the breaking of macromolecular DNA into small pieces.
Acute or chronic INFLAMMATION of the PANCREAS due to excessive ALCOHOL DRINKING. Alcoholic pancreatitis usually presents as an acute episode but it is a chronic progressive disease in alcoholics.
Compression of the ROTATOR CUFF tendons and subacromial bursa between the HUMERAL HEAD and the ACROMION of the SCAPULA. This condition is associated with subacromial BURSITIS, as well as rotator cuff (largely supraspinatus) and bicipital tendon INFLAMMATION.
Chemicals especially for use on instruments to destroy pathogenic organisms. (Boucher, Clinical Dental Terminology, 4th ed)
The number of viral particles (usually HIV) in a sample of blood plasma.
The most common kind of HIATAL HERNIA in which the ESOPHAGOGASTRIC JUNCTION slides above the DIAPHRAGM into the THORAX.
A pyrrolidine with antiepileptic activity. The exact mechanism through which levetiracetam exerts its effects is unknown but does not involve inhibitory and excitatory neurotransmitter activity. Stereoselective binding of levetiracetam was confined to synaptic plasma membranes in the central nervous system with no binding occurring in peripheral tissue. Levetiracetam inhibits burst firing without affecting normal neuronal excitability, which suggests that it may selectively prevent hyper-synchronization of epileptiform burst firing and propagation of seizure activity.
The sodium salt form of an organic phosphate compound that provides phosphate for nutritional purposes. In addition, sodium glycerophosphate can be used as a phosphate diluting agent upon internal contamination with the beta-emiting radioisotope phosphate P 32 (P-32) that competes with P-32 for absorption. As sodium glycerophosphate is administered in high amounts, the absorption of P-32 is prevented or minimalized.
The ditartrate salt of a semisynthetic vinca alkaloid derived from the leaves of the periwinkle plant (Vinca rosea) with antineoplastic properties. Vinorelbine binds to tubulin, thereby inhibiting tubulin polymerization into microtubules and spindle formation and resulting in apoptosis of susceptible cancer cells. Inhibition of mitotic microtubules correlates with antitumor activity, whereas inhibition of axonal microtubules seems to correlate with vinorelbine's neurotoxicity. Compared to related vinca alkaloids, vinorelbine is more selective against mitotic than axonal microtubules in vitro, which may account for its decreased neurotoxicity. This agent is also a radiation-sensitizing agent. (NCI04)
The orally available active prodrug of ICRF-154, a bisdioxopiperazine derivative, with cardioprotective and antineoplastic activities. Like other ICRF compounds, sobuzoxane and its active metabolite ICRF-154 interfere with topoisomerase II activity prior to the formation of intermediate cleavable DNA-enzyme complexes during the catalytic cycle resulting in tumor cell growth inhibition. Furthermore, sobuzoxane chelates metal cations thereby limiting the formation of free radical-generating anthracycline-metal complexes and may prevent anthracycline-induced oxidative damage to cardiac and soft tissues.
A synthetic recombinant form of the naturally occurring hirudin, the anticoagulant substance found in leech. Desirudin is a selective and almost irreversible inhibitor of thrombin, both free and clot-bound, by blocking its active site. This anticoagulant agent has no effect on other components of the hemostatic system. Desirudin is particularly used to prevent deep vein thrombosis in patients undergoing hip and knee replacement surgery.
A tolyl compound and leukotriene receptor antagonist (LTRA), with anti-asthmatic and potential capsular contracture-preventing activities. Upon administration, zafirlukast selectively and competitively binds to and blocks the cysteinyl leukotriene 1 receptor (CYSLTR1), thereby preventing the potent pro-inflammatory mediators leukotriene C4, D4 and E4 from binding. This prevents leukotriene-mediated actions, including enhanced migration of eosinophils and neutrophils, increased adhesion of leukocytes, increased monocyte and neutrophil aggregation, increased airway edema, inflammation, capillary permeability and bronchoconstriction. In addition, zafirlukast may decrease collagen deposition, fibrosis, and capsular thickness after implantation, thereby preventing scar tissue.
A 4-(3-methoxypropoxy)-3-methylpyridinyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.
A potent protein tyrosine kinase inhibitor that exhibits greater specificity for c-ErbB oncoprotein. (NCI)
A combination agent, comprised of belladonna alkaloids and Phenobarbital, with gastrointestinal anticholinergic activity. The belladonna alkaloids produce an anticholinergic effect by the competitive inhibition of acetylcholine at the parasympathetic neuro-effector junction, and the barbiturates produce a sedative effect probably as a result of their inhibition of synaptic neurotransmitters in the central nervous system (CNS).
A non-phenolic tyrphostin-class tyrosine kinase inhibitor that inhibits epidermal growth factor receptor, affecting cell proliferation and tumor growth in vivo. (NCI)
A disulfide-linked homodimeric protein complex comprised of 2 platelet-derived growth factor subunit B proteins. This dimeric growth factor binds to a homodimeric receptor comprised of two platelet-derived growth factor receptor beta proteins. Ligand binding activates the intrinsic tyrosine-protein kinase activity of the receptor complex and initiates signal transduction pathways.
A synthetic light-activated chlorin with photodynamic activity. Upon systemic administration, temoporfin distributes throughout the body and is taken up by tumor cells. Upon stimulation of temoporfin by non-thermal laser light (at 652 nm), and in the presence of oxygen, this agent produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to tumor cells. This may kill tumor cells and may reduce the tumor size.
A synthetic nitrogen-containing bisphosphonate. Ibandronate inhibits farnesyl pyrophosphate synthase, resulting in a reduction in geranylgeranyl GTPase signaling proteins and apoptosis of osteoclasts. This agent increases bone mineral density, decreases bone remodeling, inhibits osteoclast-mediated bone resorption, and reduces metastases-related and corticosteroid-related bone pain. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=365963&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=365963&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1670"" NCI Thesaurus)
A third-generation amino-bisphosphonate with anti-resorptive and anti-hypercalcemic activities. Ibandronic acid binds to and adsorbs onto the surface of hydroxyapatite crystals in the bone matrix, thereby preventing osteoclast resorption. This agent also inhibits farnesyl pyrophosphate synthase, an enzyme involved in the mevalonate pathway. Inhibition of this enzyme prevents the formation of isoprenoids, thereby leading to a reduction in the farnesylation and geranylgeranylation of signaling proteins of G protein-coupled signaling, and, eventually, inducing apoptosis of osteoclasts. By inhibiting osteoclast-mediated bone resorption, ibandronic acid increases bone mineral density, decreases bone remodeling and turnover, as well as reduces bone pain.
An agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic and anti-inflammatory activities. Darglitazone may be able to abrogate acute cerebral inflammatory responses via its suppression of proinflammatory gene expression.
The hydrochloride salt form of ziprasidone, a benzothiazolylpiperazine derivative and an atypical antipsychotic agent with an antischizophrenic property. Ziprasidone hydrochloride functions as an antagonist at the dopamine D2 and serotonin 5-HT2A and 5-HT1D receptors, and as an agonist at the 5-HT1A receptor. Ziprasidone hydrochloride also inhibits synaptic reuptake of serotonin and norepinephrine. The mechanism of action by which ziprasidone hydrochloride exerts its antischizophrenic effect is unknown but is potentially mediated through a combination of dopamine D2 and serotonin 5-HT2 antagonism. This agent also has antagonistic activity against histamine H1 and alpha-1-adrenergic receptors.
A benzothiazolylpiperazine derivative and an atypical antipsychotic agent with an antischizophrenic property. Ziprasidone functions as an antagonist at the dopamine D2 and serotonin 5-HT2A and 5-HT1D receptors, and as an agonist at the 5-HT1A receptor. Ziprasidone also inhibits the synaptic reuptake of serotonin and norepinephrine. The mechanism of action by which ziprasidone exerts its antischizophrenic effect is unknown but is potentially mediated through a combination of dopamine D2 and serotonin 5-HT2 antagonism. This agent also has antagonistic activity against histamine H1 and alpha-1-adrenergic receptors.
The orally bioavailable monosodium salt of montelukast, a selective cysteinyl leukotriene receptor antagonist with anti-inflammatory and bronchodilating activities. Montelukast selectively and competitively blocks the cysteinyl leukotriene 1 (CysLT1) receptor, preventing binding of the inflammatory mediator leukotriene D4 (LTD4). Inhibition of LTD4 activity results in inhibition of leukotriene-mediated inflammatory events including: migration of eosinophils and neutrophils; adhesion of leukocytes to vascular endothelium, monocyte and neutrophil aggregation; increased airway edema; increased capillary permeability; and bronchoconstriction. The CysLT1 receptor is found in a number of tissues including spleen, lung, placenta, small intestine, and nasal mucosa, and in a variety of cell types including monocyte/macrophages, mast cells, eosinophils, CD34-positive hemopoietic progenitor cells, neutrophils and endothelial cells.
A thiourea non-nucleoside reverse transcriptase inhibitor.
A potent inhibitor of epidermal growth factor receptor kinase autophosphorylation. (NCI)
The B isomer of Curacin compound. Cruacin B inhibits tubulin polymerization, thereby inhibiting mitosis and cell proliferation. (NCI)
The C isomer of Curacin compound. Cruacin C inhibits tubulin polymerization, thereby inhibiting mitosis and cell proliferation. (NCI)
The A isomer of Curacin compound. Cruacin A inhibits tubulin polymerization, thereby inhibiting mitosis and cell proliferation. (NCI)
Compounds of silver and proteins used as topical anti-infective agents.
A regulatory calcium-calmodulin-dependent protein kinase that specifically phosphorylates CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 1; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 2; CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE TYPE 4; and PROTEIN KINASE B. It is a monomeric enzyme that is encoded by at least two different genes.
A recombinant DNA-derived humanized monoclonal antibody directed against the cell surface glycoprotein, CD52. Alemtuzumab is an IgG1 kappa with human variable framework and constant regions, and complementarity-determining regions derived from a rat monoclonal antibody. This agent selectively binds to CD52, thereby triggering a host immune response that results in lysis of CD52 + cells. CD52 is a glycoprotein expressed on the surface of essentially all normal and malignant B and T cells, a majority of monocytes, macrophages and natural killer (NK) cells, a subpopulation of granulocytes, and tissues of the male reproductive system. (NCI04)
A nucleoside reverse transcriptase inhibitor analog of adenosine.
A member of the tyrphostin family of tyrosine kinase inhibitors that inhibits epidermal growth factor receptor, capacitative calcium ion entry into cells, blocks HT-29 colon cancer cell proliferation and induces non-apoptotic cell death. (NCI)
Mammalian-cell derived recombinant human growth hormone.
A benzodiazepine non-nucleoside reverse transcriptase inhibitor with activity against human immunodeficiency viruses 1 and 2 and simian immunodeficiency virus. Tivirapine inhibits replication in both wild-type and drug-resistant HIV-1 isolates.
A phenol mustard glutamate prodrug which induces apoptosis by cross-linking DNA and with potential use in Antibody Directed Enzyme Prodrug Therapy (ADEPT). (NCI)
The phenylhydrazone 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone formulated as a topical agent with immunomodulating and potential antineoplastic activities. Applied topically as a 0.25% gel, A-007 may stimulate a local immune response against human papillomavirus (HPV)-induced cervical intraepithelial neoplasia (CIN). Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=485274&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=485274&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61305"" NCI Thesaurus)
A synthetic heterocyclic pyridinium compound. MKT-077 is a water soluble lipophilic cationic molecule and an analog of rhodacyanine dye, which partitions into tumor cell mitochondria where it is thought to act as a metabolic poison, leading to G1 arrest and apoptosis. This agent also shows selective cytotoxicity to cancer cells mediated by its binding to the hsp70 family protein mot-2 and reactivation of tumor suppressor p53 function.
A synthetic imidazole derivative prodrug with an antihypertensive property. Upon hydrolysis, olmesartan medoxomil is converted to olmesartan. Olmesartan selectively binds to the angiotensin type 1 (AT1) receptor of angiotensin II in vascular smooth muscle and adrenal gland, thereby competing angiotensin II binding to the receptor. This prevents angiotensin II-induced vasoconstriction and decreases aldosterone production, thereby preventing aldosterone-stimulated sodium retention and potassium excretion.
A member of the tyrphostin family of tyrosine kinase inhibitors, which selectively inhibits HER2. (NCI)
A benzoporphyrin derivative that is used in PHOTOCHEMOTHERAPY to treat wet type MACULAR DEGENERATION.
respiratory syncytial virus immune globulin, intravenous.
A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS.
A cyclic depsipeptide isolated from the marine tunicate Aplidium albicans. Plitidepsin displays a broad spectrum of antitumor activities, inducing apoptosis by triggering mitochondrial cytochrome c release, initiating the Fas/DC95, JNK pathway and activating caspase 3 activation. This agent also inhibits elongation factor 1-a, thereby interfering with protein synthesis, and induces G1 arrest and G2 blockade, thereby inhibiting tumor cell growth.
A benzhydryl compound and a muscarinic receptor antagonist possessing both antimuscarinic and antispasmodic properties. Both tolterodine and its active metabolite, 5-hydroxymethyltolterodine, competitively blocks muscarinic receptors, thereby inhibiting acetylcholine binding. This antagonistic action results in an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, indicating an antimuscarinic action on the lower urinary tract. The 5-hydroxymethyl metabolite appears to contribute significantly to the therapeutic effects.
The dihydrochloride salt of nolatrexed, a water-soluble lipophilic quinazoline folate analog with antineoplastic activity. Nolatrexed occupies the folate binding site of thymidylate synthase, resulting in inhibition of thymidylate synthase activity and thymine nucleotide synthesis with subsequent inhibition of DNA replication, DNA damage, S-phase cell cycle arrest, and caspase-dependent apoptosis. This agent also exhibits radiosensitizing activity.
A nucleoside reverse transcriptase inhibitor analog of cytosine.
A synthetic, 20-base antisense oligodeoxynucleotide that hybridizes to c-raf kinase messenger RNA. ISIS 5132 has been shown to specifically suppress Raf-1 expression both in vitro and in vivo. Raf-1 serine/threonine kinase functions as a critical effector of Ras-mediated signal transduction; constitutive activation of this pathway directly contributes to malignant transformation. (NCI04)
A vaccinia viral based vaccine, encoding epitopes of E6 and E7 proteins from human papillomavirus (HPV) types 16 and 18, with immunostimulatory and antineoplastic activities. HPV types 16 and 18 account for approximately 70% of cervical cancers. Vaccination with this HPV-TA (tumor antigen) vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for E6 and E7 from either type 16 or 18 HPV, resulting in decreased tumor growth.
A covalent conjugate of recombinant interferon alfa, subtype 2a, and polyethylene glycol (PEG), used as an antiviral and antineoplastic agent. The biological activity of this agent is derived from its interferon alpha-2a protein moiety. Interferons alfa bind to specific cell-surface receptors, leading to the transcription and translation of genes whose protein products mediate antiviral, antiproliferative, anticancer and immune-modulating effects. The PEG moiety lowers the clearance of interferon alpha-2a, thereby extending the duration of its therapeutic effects, but may also reduce interferon-mediated stimulation of an immune response. (NCI04)
A lipophilic antioxidant with both antiproliferative and lipid-lowering properties. Treatment with nicanartine both decreases plasma LDL cholesterol and increases plasma HDL cholesterol.
An inhibitor of histone deacetylase. It is an aromatic sulfonamide hydroxamate initially found in a screen for inhibitors of the tumorigenic phenotype of K-ras-transformed NIH3T3 cells.
A benzopyran lacking the indole ring of the triptans with vasoconstrictor activity. Alnitidan selectively binds to and activates serotonin 5-HT 1B and 1D receptors in the central nervous system (CNS), thereby causing extracerebral, intracranial blood vessel constriction. This may lead to pain relief from vascular headaches. Furthermore, alniditan may potentially reduce plasma protein extravasation, which may be another mechanism by which this agent relieves vascular headaches.
Tietz syndrome is a disorder characterized by profound hearing loss from birth, fair skin, and light-colored hair. The hearing loss in affected individuals is caused by abnormalities of the inner ear (sensorineural hearing loss) and is present from birth. Although people with Tietz syndrome are born with white hair and very pale skin, their hair color often darkens over time to blond or red. The skin of affected individuals, which sunburns very easily, may tan slightly or develop reddish freckles with limited sun exposure; however, their skin and hair color remain lighter than those of other members of their family.Tietz syndrome also affects the eyes. The colored part of the eye (the iris) in affected individuals is blue, and specialized cells in the eye called retinal pigment epithelial cells lack their normal pigment. The retinal pigment epithelium nourishes the retina, the part of the eye that detects light and color. The changes to the retinal pigment epithelium are generally detectable only by an eye examination; it is unclear whether the changes affect vision.
A benign, WHO grade I cerebellar mass, which occurs in young adults and is composed of dysplastic ganglion cells. It is the major CNS manifestation of Cowden disease, an autosomal dominant condition that causes a variety of hamartomas and neoplasms.
A reduction in the normal physical activity for an individual.
Polycythemia that is caused by excess erythropoietin.
An abnormality of erythrocytes (red-blood cells).
A non-midline cleft of the upper lip on the left and right sides.
A non-midline cleft of the upper lip on one side only.
pathologic processes that affect patients after administration of anesthesia.
Increasing girth of the mid section of an individual.
Ischemic necrosis of the testis usually caused by torsion of the spermatic cord, trauma, or severe epididymo-orchitis.
A premalignant pathologic process that affects the mucosal epithelium of the larynx. It appears as a localized or diffuse white patch on the laryngeal mucosa. Morphologically it is characterized by the pathologic production of keratin in the mucosal epithelial surface with or without epithelial atypia. It may progress to or co-exist with invasive squamous cell carcinoma.
A form of lymphadenitis that is characterized by formation of pus; it is most often caused by staphylococcal or streptococcal bacteria.
The presence of more than one genetically distinct cell line in germ and/or somatic cells.
Sarcoidosis affecting the tissues of the heart.
An uncomfortable feeling of inner restlessness and inability to stay still. It can be a side effect of psychotropic medications.
An erosion or abrasion of the cornea's outermost layer of epithelial cells.
Complaints describing a pattern similar to influenza, which may include one or more of the following symptoms: fever, chills, muscle or body aches, cough, sore throat, rhinitis, or fatigue.
Repetition of one's own words or phrases. [PMID:27527544]
Abnormality of REM sleep. Phases of REM sleep are characterized by desynchronized EEG patterns, increases in heart rate and blood pressure, sympathetic activation, and a profound loss of muscle tonus except for the eye and middle-ear muscles. There are then phases of rapid eye movements.
Inflammation of the mouth mucosa caused by head and neck radiation therapy. Signs and symptoms include dry mouth due to lack of saliva, mucosal ulcerations and diffuse erythema of the mouth, taste alteration, and dysphagia.
inhibitor of purine nucleoside synthesis.
State of the body in relation to the consumption and utilization of nutrients.
A viral (such as mumps) or bacterial infectious process affecting the salivary gland. The salivary gland becomes enlarged and is often painful.
A subtype of schizophrenia in which the individual exhibits the characteristic symptoms of schizophrenia but the overall picture is not one of catatonic type, paranoid type, or disorganized type schizophrenia.
Derivation of pleasure from infliction of physical or mental pain on others and oneself, with presence of high degree of destructiveness.
A state of emotional depression which may result in a negative outlook on life.
A laboratory test result indicating that there is an abnormally small number of platelets in the circulating blood.
A malignant neoplasm that arises from the mesothelial cells. Histologic variants include biphasic, epithelioid, sarcomatoid, and desmoplastic mesothelioma.
A type of linear scleroderma characterized by a linear, colorless, atrophied band across the forehead or scalp. This disorder can affect the tissues under or near the lesion including brain, bone and eyes.
Softening of the skull seen in newborns due to incomplete mineralization.
A localized outpouching of ventricular cavity that is generally associated with dyskinesia and paradoxical expansion during systole.
Formation of blood clot in the lumen of the abdominal aorta. It may lead to severe abdominal pain and ischemic necrosis of the intestine.
Roberts syndrome (RBS) is characterized by prenatal growth retardation (ranging from mild to severe), craniofacial findings (including microcephaly and cleft lip and/or palate) and limb malformations (including bilateral symmetric tetraphocomelia or hypomelia caused by mesomelic shortening). Upper limbs are more severely affected than lower limbs. Other limb malformations include oligodactyly with thumb aplasia or hypoplasia, syndactyly, clinodactyly, and elbow and knee flexion contractures. Craniofacial abnormalities include cleft lip and/or cleft palate, premaxillary prominence, micrognathia, microbrachycephaly, malar flattening, downslanted palpebral fissures, widely spaced eyes, exophthalmos resulting from shallow orbits, corneal clouding, underdeveloped ala nasi, beaked nose, and ear malformations. Intellectual disability is reported in the majority of affected individuals. Mortality is high among severely affected pregnancies and newborns. Mildly affected individuals may survive to adulthood.
Complete absence of the interatrial septum with common atrioventricular valve and two atrioventricular connections.
HFE hemochromatosis is characterized by inappropriately high absorption of iron by the small intestinal mucosa. The phenotypic spectrum of HFE hemochromatosis includes: Persons with clinical HFE hemochromatosis, in whom manifestations of end-organ damage secondary to iron overload are present; Individuals with biochemical HFE hemochromatosis, in whom transferrin-iron saturation is increased and the only evidence of iron overload is increased serum ferritin concentration; and Non-expressing p.Cys282Tyr homozygotes, in whom neither clinical manifestations of HFE hemochromatosis nor iron overload are present. Clinical HFE hemochromatosis is characterized by excessive storage of iron in the liver, skin, pancreas, heart, joints, and anterior pituitary gland. In untreated individuals, early symptoms include: abdominal pain, weakness, lethargy, weight loss, arthralgias, diabetes mellitus; and increased risk of cirrhosis when the serum ferritin is higher than 1,000 ng/mL. Other findings may include progressive increase in skin pigmentation, congestive heart failure, and/or arrhythmias, arthritis, and hypogonadism. Clinical HFE hemochromatosis is more common in men than women.
A rare neurologic disorder caused by impingement of the nerve roots of the cauda equina secondary to disc herniation, spinal stenosis, vertebral fracture, neoplasm or infection. Clinical signs may include bladder or bowel dysfunction, paresthesia and weakness of the lower extremities. The clinical course rapidly deteriorates and necessitates emergent surgical decompression to minimize risk of incontinence, sexual dysfunction and permanent paralysis.
A cataract involving the nucleus of the lens
An acquired coagulation disorder characterized by the partial or complete absence of prothrombin (factor II) activity in the blood.
A neuroma that occurs at the site of an amputation.
Any infection documented following a surgical procedure that was not evident or suspected prior to the procedure.
and that is acquired by the ingestion of the infective larvae on vegetables or in raw or undercooked snails, slugs, land crabs, freshwater shrimps, frogs and lizards. The main feature is eosinophilic meningitis, with clinical manifestations including fever, headache, malaise, fatigue, vomiting, rhinorrhea, blurred vision, diplopia, cough, stiff neck, enteritis, constipation and paraesthesia due to the movement of the worms from the intestines to the lungs, central nervous system and eyes. In severe cases without treatment, coma and death can occur.
Extreme elevation of body temperature above normal.
Abnormal functioning of the swallowing mechanism associated with deficits in oral, pharyngeal, or esophageal structure or function.
Abnormal sensations with no apparent physical cause that are painful or unpleasant.
dyskinesia due to extrapyramidal disorder; as a general rule, symptoms are absent during sleep, reduced with relaxation, and increased with stress.
Unsteadiness or trembling movements of the whole body or a body part.
A genetic predisposition to form IgE antibodies in response to exposure to allergens and therefore, for the development of immediate (type I) hypersensitivity and atopic conditions, such as allergic rhinitis; bronchial asthma, atopic dermatitis, and food allergy. Mutations of specific alleles on the long arm of chromosome 5 have been associated with higher levels of IL-4 and IgE and are known as IL-4 promoter polymorphisms.
A kind of anemia characterized by inadequate production of erythrocytes.
A disorder of large arteries, in particular the aorta, characterized by an accumulation of basophilic ground substance in the media with cyst-like lesions associated with degenerative changes of collagen, elastin and the vascular smooth muscle cells.
A localized skin condition commonly associated with sun exposure that is characterized by variegated discoloration, telangiectasia and atrophy.
A low grade fibroblastic neoplasm presenting as a nodular cutaneous mass, most often on the trunk and the proximal extremities. The tumor diffusely infiltrates the dermis and the subcutaneous tissues. It is considered a locally aggressive neoplasm, which often recurs but rarely metastasizes.
An aggressive, predominantly extranodal, mature T-cell non-Hodgkin lymphoma. It is characterized by an often angiocentric and angiodestructive cellular infiltrate composed of EBV positive NK/T cells. The nasal cavity is the most common site of involvement. Patients often present with midfacial destructive lesions (lethal midline granuloma). The disease may disseminate rapidly to various anatomic sites including the gastrointestinal tract, skin, testis, and cervical lymph nodes. It is also known as angiocentric T-cell lymphoma. The term ""polymorphic reticulosis"" has been widely used to describe the morphologic changes seen in this type of lymphoma. However, the latter term may also apply to lymphomatoid granulomatosis, which is an angiocentric and angiodestructive EBV positive B-cell lymphoproliferative disorder.
The brand name for zoledronic acid, a bisphosphonic imidazol compound which inhibits osteoclastic bone resorption. Although its mechanisms of action is yet to be fully characterized, zoledronic acid appears to directly inhibit osteoclast function and trigger osteoclast apoptotic cell death, thereby decreasing the osteoclast stimulation and bone calcium loss induced by various tumor-associated cytokines. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42507&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42507&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1699"" NCI Thesaurus)
A recombinantly produced form of human thrombopoietin (rHuTPO). rHuTPO stimulates platelet formation and has potential use as a therapeutic agent to prevent thrombocytopenia in patients receiving chemotherapy.
The F(ab)2 fragment of Me1-14, a murine IgG2a monoclonal antibody directed against proteoglycan chondroitin sulfate-associated protein expressed by gliomas and melanomas. By binding to proteoglycan chondroitin sulfate-associated protein, monoclonal antibody Me1-14 F(ab')2 conjugated to a radioisotope may localize gliomas and melanomas when used as a tracer in radioimaging applications; in radioimmunotherapeutic applications, this agent conjugated to a radioisotope may be used to deliver targeted radiotoxicity to these tumors.
A humanized monoclonal antibody directed against the human A33 antigen. Monoclonal antibody A33 recognizes the human A33 antigen, a 43 KDa transmembrane glycoprotein of the immunoglobulin superfamily, which is highly and homogenously expressed in 95% of colorectal cancer metastases with only restricted expression in normal colonic mucosa.
A substance being studied in the treatment of some types of cancer. CEP-2563 dihydrochloride blocks certain proteins involved in the growth of some tumors and may kill cancer cells. It is a type of receptor tyrosine kinase inhibitor.
A highly aggressive malignant neoplasm arising from the ovary. Morphologically, it is a high grade tumor, composed of carcinomatous and sarcomatous elements.
A cocktail preparation of synthetic interleukin (IL) -1, IL-2, IL-6, tumor necrosis factor (TNF)-alpha, interferon gamma and other cytokines that are chemically identical to or similar to signaling molecules secreted by leukocyte cells. Leukocyte interleukins are essential in many immune responses, such as antibodies production, modulating secretion of other cytokines, and activation of bone marrow stem cells.
The potassium salt of oxonate, an enzyme inhibitor that modulates 5- fluorouracil (5-FU) toxicity. Potassium oxonate inhibits orotate phosphoribosyltransferase, which catalyzes the conversion of 5-FU to its active or phosphorylated form, FUMP. Upon oral administration, Oxonate is selectively distributed to the intracellular sites of tissues lining the small intestines, producing localized inhibitory effects within the gastrointestinal tract. As a result, 5-FU associated gastrointestinal toxic effects are reduced and the incidence of diarrhea or mucositis is decreased in 5-FU related therapy.
A formal ranking system of the strength of evidence linked to a reported result.
The F(ab)2 fragment of monoclonal antibody (MoAb) MX35 that recognizes a 95 kD glycoprotein with homogeneous distribution on 80% of ovarian tumor specimens. When radiolabeled, this MoAb has potential use in the radioimaging or may induce a cytotoxic T-cell response against tumor cells that express this glycoprotein. Containing only the antigen-binding fragment of the Ig molecule, MoAb MX35 F(ab')2 offers the advantages of smaller size and lower cross-reactivity compared to complete antibodies.
A vaccine made by putting the gene for carcinoembryonic antigen (CEA) into the vaccinia virus. The vaccinia virus is related to the virus used to make the smallpox vaccine. CEA is a tumor marker. The vaccinia CEA vaccine may help the immune system recognize and kill cancer cells that make CEA.
A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.
E1A gene combined with lipids that serve as a means to deliver the E1A gene into the cancer cells. The combination of lipids and the E1A gene is called the E1A Lipid Complex.
A radioimmunoconjugate of a murine whole immunoglobulin G monoclonal antibody MAb-170 labeled with Technetium 99m (Tc-99m). MAb-170, originally raised against a carbohydrate epitope (a synthetic Thomsen-Friedenreich antigen), has been found to have panadenocarcinoma affinity, including adenocarcinomas of breast, fallopian tube, colon, endometrium, prostate, bladder, liver, lung, and ovary. Tc-99m MAb-170 delivers gamma emission Tc-99m nuclide directly to adenocarcinoma tissues, thereby this agent may be used for diagnostic or imaging purposes.
A fluoronucleoside that inhibits pyrimidine synthesis, interfering with DNA synthesis.
A genetically-engineered adenovirus that contains the gene that encodes the human tumor-suppressor protein p53 with potential antineoplastic activity. Recombinant adenovirus-p53 SCH-58500 delivers p53 into tumor cells, which may result in p53-mediated cell cycle arrest and apoptosis.
A recombinant monoclonal antibody in which the heavy and light chain variable domains mimic a specific epitope of the tumor-associated protein carcinoembryonic antigen (CEA). This agent is used as a cancer vaccine against tumors that express CEA. (NCI04)
A detoxified, nonspecific immunostimulant consisting of a combination of the active monophosphoryl lipid A component of lipopolysaccharide (LPS) isolated from the bacterium Salmonella minnesota combined with a residue of the cell wall of the bacterium Mycobacterium phlei. Detox-PC differs from Detox adjuvant and Detox-B in that Detox-PC contains egg phosphatidylcholine and alpha-tocopherol. (NCI04)
A cancer vaccine consisting of dendritic cells harvested from a patient with cancer and pulsed or transduced with a peptide fragment of MART-1 (melanoma antigen recognized by T-cells), an antigen expressed by melanoma cells. When the altered dendritic cells are returned to the patient, they stimulate the host immune system to mount a cytotoxic T-lymphocyte immune response against tumor cells expressing MART-1. (NCI04)
A cell-based cancer vaccine with potential antineoplastic activity. PA-1-STK ovarian carcinoma vaccine is produced by transducing the ovarian cancer cell line, PA-1, with the herpes simplex thymidine kinase (HSV-tk) gene, resulting in a cell line, PA-1-STK, that permanently expresses the HSV tk gene. Upon transfection into malignant cells, this vaccine is capable of sensitizing tumor cells in response to an antiviral drug such as ganciclovir, which is readily phosphorylated by the TK enzyme to its active form. Administration of ganciclovir following PA-1 STK transfection results in enhanced cytotoxicity of the transfected tumor cells. Additionally, adjacent non-transfected cells are also killed by the activated antiviral drug, a phenomenon referred to as the bystander effect that occurs with this type of suicide-gene transfer technique.
Non-Hodgkin lymphoma that occurs during pregnancy.
An autologous sarcoma cell vaccine with potential immunostimulatory activity. Tumor cells harvested from a patient with sarcoma are transfected with a plasmid DNA encoding for human sargramostim (GM-CSF) using a particle-mediated gene transfer (PMGT) technique, which avoids the use of infectious components. Vaccination with an autologous sargramostim sarcoma vaccine produces high levels of GM-CSF, a cytokine that enhances antigen presentation by activated macrophages and increases the recognition of weakly immunogenic tumors by cytotoxic T-lymphocytes.
A vaccine adjuvant consisting of a plasmid DNA encoding sargramostim (a granulocyte macrophage-colony stimulating factor). Upon administration, expressed sargramostim may stimulate a cytotoxic T cell response enhancing the host immune response to a concomitantly administered melanoma vaccine.
A radioimmunoconjugate consisting of 3F8, a murine anti-GD2 ganglioside monoclonal antibody labeled with iodine 131 (I-131), with radioimaging and radioimmunotherapeutic properties. Using monoclonal antibody 3F8 as a carrier for I-131 results in the targeted imaging and/or destruction of cells expressing GD2. GD2 is a ganglioside which is overexpressed in malignant melanoma, neuroblastoma, and small cell carcinoma of the lung. (NCI04)
An autologous cancer vaccine derived from tumor-specific gp96 heat shock proteins. Heat shock proteins chaperone peptides through the endoplasmic reticulum, are key regulators of dendritic cell maturation, migration and antigen processing, and are involved in T-cell activation. (NCI04)
A gene transfer agent comprised of murine packaging cell lines, psiCRIP, and an engineered retroviral vector MFG-S containing the coding region of amino acid residues from 1-67 of HSV Thymidine Kinase which allows gene transfer to occur without viral replication in transduced cells and has been used as a selection marker with ganciclovir treatment.
A synthetic triazole with antifungal activity. Voriconazole selectively inhibits 14-alpha-lanosterol demethylation in fungi, preventing the production of ergosterol, an essential constituent of the fungal cell membrane, and resulting in fungal cell lysis. (NCI04)
A vaccine consisting of recombinant vaccinia virus encoding prostate specific antigen (PSA). Vaccination with recombinant vaccinia prostate-specific antigen vaccine stimulates the host immune system to mount a cytotoxic T-cell response against tumor cells expressing PSA.
Meningitis that persists for more than 4 weeks, and lymphocytes are present in the cerebrospinal fluid (CSF).
A rare, immune-mediated disorder characterized by cerebellar degeneration due to the presence of an often undetected malignancy (usually carcinoma or lymphoma) in an anatomic site other than the cerebellum. Signs and symptoms include progressive ataxia, dysarthria, and nystagmus.
Troyer syndrome is characterized by progressive spastic paraparesis, dysarthria, and pseudobulbar palsy; distal amyotrophy; motor and cognitive delays; short stature; and subtle skeletal abnormalities. Most affected children exhibit delays in walking and talking followed by slow deterioration in both gait and speech. Emotional lability and affective disorders, such as inappropriate euphoria and/or crying, are common. Mild cerebellar signs are common. The most severely affected individuals have choreoathetosis. Life expectancy is normal.
A progressive neurodegenerative condition affecting the cerebral cortex and basal ganglia. The disorder is characterized by varying degrees of cognitive and motor impairment.
A rare neurodegenerative disorder characterized by loss of autonomic nervous system functions and disturbances of motor, balance and muscle coordination.
Chorea-acanthocytosis (ChAc) is characterized by a progressive movement disorder, cognitive and behavior changes, a myopathy that can be subclinical, and chronic hyperCKemia in serum. Although the disorder is named for acanthocytosis of the red blood cells, this feature is variable. The movement disorder is mostly limb chorea, but some individuals present with parkinsonism. Dystonia is common and affects the oral region and especially the tongue, causing dysarthria and serious dysphagia with resultant weight loss. Habitual tongue and lip biting are characteristic, as well as tongue protrusion dystonia. Progressive cognitive and behavioral changes resemble those in a frontal lobe syndrome. Seizures are observed in almost half of affected individuals and can be the initial manifestation. Myopathy results in progressive distal muscle wasting and weakness. Mean age of onset in ChAc is about 30 years, although ChAc can develop as early as the first decade or as late as the seventh decade. It runs a chronic progressive course and may lead to major disability within a few years. Life expectancy is reduced, with age of death ranging from 28 to 61 years.
Neurodegeneration involving the globus pallidus,a part of the basal ganglia that is involved in the regulation of voluntary movement.
NKX2-1-related disorders range from benign hereditary chorea (BHC) to choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress (also known as brain-lung-thyroid syndrome). Childhood-onset chorea, the hallmark of NKX2-1-related disorders, may or may not be associated with respiratory distress syndrome or congenital hypothyroidism. Chorea generally begins in early infancy or about age one year (most commonly) or in late childhood or adolescence, and progresses into the second decade after which it remains static or (rarely) remits. Pulmonary disease, the second most common manifestation, can include respiratory distress syndrome in neonates, interstitial lung disease in young children, and pulmonary fibrosis in older persons. The risk for pulmonary carcinoma is increased in young adults with an NKX2-1-related disorder. Thyroid dysfunction, the result of dysembryogenesis, can present as congenital hypothyroidism or compensated hypothyroidism. The risk for thyroid cancer is unknown and may not be increased. In one review, 50% of affected individuals had the full brain-lung-thyroid syndrome, 30% had involvement of brain and thyroid only, and 13% had isolated chorea only.
A form of dystonia characterized by episodes of dystonia (often hemidystonia or generalized) lasting from minutes to hours. There are no dystonic symptoms between episodes.
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.
A movement disorder characterized by sustained or intermittent muscle contractions, resulting in abnormal movements and/or postures.
A combination of opsoclonus (involuntary conjugate eye movements of large amplitude) and myoclonic jerks. This can be a paraneoplastic syndrome (a result of brain metastasis) or post-infectious (viral encephalitis).
Inflammation of the brain secondary to an immune response triggered by the body itself.
Acute neurological dysfunction during severe SEPSIS in the absence of direct brain infection characterized by systemic inflammation and BLOOD BRAIN BARRIER perturbation.
A form of multiple sclerosis characterized by a progressive deterioration in neurologic function which is in contrast to the more typical relapsing remitting form. If the clinical course is free of distinct remissions, it is referred to as primary progressive multiple sclerosis. When the progressive decline is punctuated by acute exacerbations, it is referred to as progressive relapsing multiple sclerosis. The term secondary progressive multiple sclerosis is used when relapsing remitting multiple sclerosis evolves into the chronic progressive form. (From Ann Neurol 1994;36 Suppl:S73-S79; Adams et al., Principles of Neurology, 6th ed, pp903-914)
Seizures with sudden loss or diminution of muscle tone with a preceding myoclonic or tonic event lasting one to two seconds or more, involving head, trunk, jaw or limb musculature.
A neurological disorder characterized by recurring seizures presenting within the first three months of life, progressive cerebral dysfunction, and an EEG pattern of periods of low electrical brain activity interspersed with bursts of high spiky activity.
Various conditions with the symptom of HEADACHE. Headache disorders are classified into major groups, such as PRIMARY HEADACHE DISORDERS (based on characteristics of their headache symptoms) and SECONDARY HEADACHE DISORDERS (based on their etiologies). (International Classification of Headache Disorders, 2nd ed. Cephalalgia 2004: suppl 1)
Headache resulting from pressure applied to the cutaneous nerves of the head.
The International Headache Society (1988) classifies headache associated with sexual activity (HSA) as an idiopathic headache under 'miscellaneous headaches unassociated with structural lesions.' Based on initial descriptions, 3 subtypes are differentiated: type 1 is a dull ache in the head and neck that slowly intensifies as sexual excitement increases, and is believed to be caused by muscle contraction similar to tension-type headache; type 2, also called 'vascular-type,' is a sudden severe, explosive headache occurring at orgasm, which may be due to increased intracranial pressure; type 3, the most uncommon type, is a postural headache resembling that caused by decreased CSF pressure, perhaps due to a meningeal tear during coitus (summary by Frese et al., 2003).
A subtype of circadian rhythm sleep disorder in which the individual exhibits a persistent pattern of late sleep onset and late awakening, which results from an endogenous sleep-wake cycle that is delayed relative to the societal norm.
A subtype of circadian rhythm sleep disorder in which the individual exhibits a normal endogenous pattern of sleep and wakefulness, but this pattern comes into conflict with the desired pattern of sleep and wakefulness required by shift work.
A parasomnia characterized by paroxysmal episodes of choreoathetotic, ballistic, dystonic movements, and semipurposeful activity. The episodes occur during non-rapid eye movement sleep and typically recur several times per night. (Neurology 1992 Jul;42(7 Suppl 6):61-67; Adams et al., Principles of Neurology, 6th ed, p391)
Partial or complete paralysis of the facial muscles of one side of an individual's face that is present at birth. It is caused by damage to the seventh cranial nerve.
A variant of the GUILLAIN-BARRE SYNDROME characterized by the acute onset of oculomotor dysfunction, ataxia, and loss of deep tendon reflexes with relative sparing of strength in the extremities and trunk. The ataxia is produced by peripheral sensory nerve dysfunction and not by cerebellar injury. Facial weakness and sensory loss may also occur. The process is mediated by autoantibodies directed against a component of myelin found in peripheral nerves. (Adams et al., Principles of Neurology, 6th ed, p1313; Neurology 1987 Sep;37(9):1493-8)
Hereditary motor and sensory neuropathy type VI is an autosomal dominant neurologic disorder characterized by peripheral neuropathy and optic atrophy (summary by Voo et al., 2003). Genetic Heterogeneity of Hereditary Motor and Sensory Neuropathy Type VI See also HMSN6B (616505), caused by mutation in the SLC25A46 gene (610826) on chromosome 5q22. For a general phenotypic description and a discussion of genetic heterogeneity of CMT, see CMT1B (118200).
Charcot-Marie-Tooth neuropathy X type 1 (CMTX1) is characterized by a moderate to severe motor and sensory neuropathy in affected males and usually mild to no symptoms in carrier females. Sensorineural deafness and central nervous system symptoms also occur in some families.
Hereditary neuropathy with liability to pressure palsies (HNPP) is characterized by repeated focal pressure neuropathies such as carpal tunnel syndrome and peroneal palsy with foot drop. The first attack usually occurs in the second or third decade. Recovery from acute neuropathy is often complete; when recovery is not complete, the resulting disability is usually mild. Some affected individuals also have signs of a mild to moderate peripheral neuropathy.
Congenital hypomyelinating neuropathy (CHN) is characterized clinically by onset of hypotonia at birth, areflexia, distal muscle weakness, and very slow nerve conduction velocities (often less than 10 m/s). Warner et al. (1997, 1998) noted that pathologic findings on sural nerve biopsies show hypomyelination of most or all fibers. Based on these findings, CHN is considered to be a result of congenital impairment in myelin formation. There has been some controversy and difficulty in differentiating congenital hypomyelination from Dejerine-Sottas syndrome (DSS; 145900) because there is considerable overlap in clinical presentation. Based on pathologic findings of sural nerve biopsies (the absence of active myelin breakdown and the paucity of the onion bulbs in CHN and the presence of demyelination/remyelination and an abundance of well-organized onion bulbs in DSS; see Balestrini et al., 1991), CHN is considered to result from a congenital impairment in myelin formation, whereas DSS is thought to be due to aberrant demyelination and subsequent remyelination of the peripheral nerve. There is also variation in the prognosis of patients diagnosed with CHN. In patients with CHN, Harati and Butler (1985) showed correlation of morbidity and mortality with the presence/absence of onion bulbs: patients with few onion bulbs died in early infancy, usually because of difficulty in swallowing and respiration after birth. Patients with atypical onion bulbs survived but were affected with severe motor and sensory impairment. These differences in outcome may represent genetic heterogeneity such that mutations in essential early myelin gene(s) cause a severe phenotype, whereas mutations in other, possibly later acting gene(s), such as MPZ, lead to a less severe outcome. Genetic Heterogeneity of Congenital Hypomyelinating Neuropathy See also CHN2 (618184), caused by mutation in the MPZ gene (159440) on chromosome 1q23; and CHN3 (618186), caused by mutation in the CNTNAP1 gene (602346) on chromosome 17q21.
A slowly progressive autoimmune demyelinating disease of peripheral nerves and nerve roots. Clinical manifestations include weakness and sensory loss in the extremities and enlargement of peripheral nerves. The course may be relapsing-remitting or demonstrate a step-wise progression. Protein is usually elevated in the spinal fluid and cranial nerves are typically spared. GUILLAIN-BARRE SYNDROME features a relatively rapid progression of disease which distinguishes it from this condition. (Adams et al., Principles of Neurology, 6th ed, p1337)
An entrapment neuropathy of the suprascapular nerve, presenting with shoulder weakness confined to the supraspinatus muscle (this muscle initiates shoulder abduction) or to the infraspinatus (this muscle externally rotates the arm), as well as with pain in the posterior part of the shoulder and upper periscapular region.
A degenerative disease of the AUTONOMIC NERVOUS SYSTEM that is characterized by idiopathic ORTHOSTATIC HYPOTENSION and a greatly reduced level of CATECHOLAMINES. No other neurological deficits are present.
Congenital myasthenic syndromes (designated as CMS throughout this entry) are characterized by fatigable weakness of skeletal muscle (e.g., ocular, bulbar, limb muscles) with onset at or shortly after birth or in early childhood; rarely, symptoms may not manifest until later in childhood. Cardiac and smooth muscle are usually not involved. Severity and course of disease are highly variable, ranging from minor symptoms to progressive disabling weakness. In some subtypes of CMS, myasthenic symptoms may be mild, but sudden severe exacerbations of weakness or even sudden episodes of respiratory insufficiency may be precipitated by fever, infections, or excitement. Major findings of the neonatal-onset subtype include: respiratory insufficiency with sudden apnea and cyanosis; feeding difficulties; poor suck and cry; choking spells; eyelid ptosis; and facial, bulbar, and generalized weakness. Arthrogryposis multiplex congenita may also be present. Stridor in infancy may be an important clue to CMS. Later childhood-onset subtypes show abnormal muscle fatigability with difficulty in activities such as running or climbing stairs; motor milestones may be delayed; fluctuating eyelid ptosis and fixed or fluctuating extraocular muscle weakness are common presentations.
A form of spastic cerebral palsy affecting all four limbs; the term bilateral hemiplegia may also be used when one side has a significantly different tone compared with the other.
Cerebral palsy (CP) is defined as a nonprogressive but not unchanging disorder of posture or movement, caused by an abnormality of the brain and first evident at the stage of rapid brain development (Hughes and Newton, 1992). It is a common disorder of childhood, with an incidence of 1 in 250 to 1,000 births (Pharoah et al., 1987; Bundey and Alam, 1993). Ataxic cerebral palsy accounts for 5 to 10% of all forms of CP, and approximately 50% of ataxic CP is thought to be inherited as an autosomal recessive trait (McHale et al., 2000). Also see spastic cerebral palsy (603513).
VLDLR-associated cerebellar hypoplasia is an inherited condition that affects the development of the brain. People with this condition have an unusually small and underdeveloped cerebellum, which is the part of the brain that coordinates movement. This brain malformation leads to problems with balance and coordination (ataxia) that become apparent in infancy and remain stable over time. Children with VLDLR-associated cerebellar hypoplasia may learn to walk later in childhood, usually after the age of 6, although some are never able to walk independently. In one Turkish family, affected people walk on their hands and feet (quadrupedal locomotion).Additional features of VLDLR-associated cerebellar hypoplasia include moderate to profound intellectual disability, impaired speech (dysarthria) or a lack of speech, and eyes that do not look in the same direction (strabismus). Some affected individuals have also had flat feet (pes planus), seizures, and short stature. Studies suggest that VLDLR-associated cerebellar hypoplasia does not significantly affect a person's life expectancy.
A form of non-spastic cerebral palsy with decreased muscle tone; noticeably ""floppy"" muscles with poor or no head control
Prolonged unconsciousness from which the individual cannot be aroused, associated with traumatic injuries to the BRAIN. This may be defined as unconsciousness persisting for 6 hours or longer. Coma results from injury to both cerebral hemispheres or the RETICULAR FORMATION of the BRAIN STEM. Contributing mechanisms include DIFFUSE AXONAL INJURY and BRAIN EDEMA. (From J Neurotrauma 1997 Oct;14(10):699-713)
Temporary mental disturbance marked by muscle incoordination and paresis as the result of excessive alcohol ingestion.
A clinical disorder characterized by excessive fluid intake (polydipsia); HYPONATREMIA; and POLYURIA in SCHIZOPHRENIA and other psychiatric disorders. Impaired water metabolism in psychogenic polydipsia can result in WATER INTOXICATION.
An abnormal narrowing of the external auditory canal.
Syndromes associated with hearing loss or progressive or late-onset hearing loss, such as neurofibromatosis, osteopetrosis, and Usher syndrome; other frequently identified syndromes include Waardenburg, Alport, Pendred, and Jervell and Lange-Nielson.
An abnormal communication between the skin and the pharynx.
A non-neoplastic growth in the vocal cord. It is characterized by tissue swelling in both vocal cords in a symmetrical manner. It is caused by vocal abuse behavior. Hoarseness is the presenting symptom.
Laryngeal abductor paralysis is an autosomal dominant condition characterized by variable penetrance and expressivity ranging from mild symptoms to neonatal asphyxia. (summary by Morelli et al., 1982; Manaligod and Smith, 1998).
Bowing (abnormal curvature) of the vocal folds.
Obstruction of the intestine due to abnormally thick meconium.
Respiratory failure due to a high level of carbon dioxide in the blood.
A saccular or fusiform dilation and elongation of the ductus arteriosus.
A benign and self-limited localized disorder characterized by histiocytic proliferation and necrotic changes in the lymph nodes. It is rarely associated with lupus erythematosus. Signs and symptoms include localized lymphadenitis, fever, and leucopenia.
Congenital or acquired structural abnormalities of the lymphatic system (LYMPHOID TISSUE) including the lymph vessels.
Disorder of adipose tissue characterized by symmetric and bilateral enlargement of the lower extremities due to abnormal deposition of SUBCUTANEOUS FAT often in obese women. It is associated with HEMATOMA, pain and may progress to secondary LYMPHEDEMA which is known as lipolymphedema.
The loss of lymph into the surrounding tissue or body cavity.
A rare, neonatal syndrome characterized by early jaundice that becomes rapidly associated with severe hemolytic anemia. The peripheral blood smear is remarkable for small irregular, contracted red blood cells with hyper-dense spikes (pyknocytes), that progressively increase in number and then spontaneously disappear.
A rare, autosomal recessive, inherited disorder caused by mutation of the GPI gene. It is characterized by chronic, non-spherocytic hemolytic anemia.
A rare, autosomal recessive, inherited disorder caused by mutation of the HK1 gene. It is characterized by the early-onset of severe, non-spherocytic hemolytic anemia.
McLeod neuroacanthocytosis syndrome (designated as MLS throughout this review) is a multisystem disorder with central nervous system (CNS), neuromuscular, and hematologic manifestations in males. CNS manifestations are a neurodegenerative basal ganglia disease including (1) movement disorders, (2) cognitive alterations, and (3) psychiatric symptoms. Neuromuscular manifestations include a (mostly subclinical) sensorimotor axonopathy and muscle weakness or atrophy of different degrees. Hematologically, MLS is defined as a specific blood group phenotype (named after the first proband, Hugh McLeod) that results from absent expression of the Kx erythrocyte antigen and weakened expression of Kell blood group antigens. The hematologic manifestations are red blood cell acanthocytosis and compensated hemolysis. Allo-antibodies in the Kell and Kx blood group system can cause strong reactions to transfusions of incompatible blood and severe anemia in newborns of Kell-negative mothers. Females heterozygous for XK pathogenic variants have mosaicism for the Kell and Kx blood group antigens but usually lack CNS and neuromuscular manifestations; however, some heterozygous females may develop clinical manifestations including chorea or late-onset cognitive decline.
An acquired coagulation disorder characterized by the partial or complete absence of factor IX activity in the blood.
A condition characterized by an abnormally high level of thrombi. Causes include thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, bone marrow disorders, and antiphospholipid antibody syndrome.
A rare thrombophilia disorder characterized by deficiency of protein C. It results in venous thromboembolism.
Heparin cofactor II (HCF2; 142360) rapidly inhibits thrombin in plasma in the presence of dermatan sulfate or heparin. Congenital HCF2 deficiency is associated with thromboembolism and is classified into type I (quantitative) or type II (qualitative) deficiency (Kondo et al., 1996).
Thrombocytopenia related to lack of or severe reduction in the count of megakaryocytes.
An autosomal dominant disorder characterized by thrombocytopenia, giant platelets, nephritis, and deafness; it is associated with mutation of the MYH9 gene.
Immune thrombocytopenia is a disorder characterized by a blood abnormality called thrombocytopenia, which is a shortage of blood cell fragments called platelets that are needed for normal blood clotting.Affected individuals can develop red or purple spots on the skin caused by bleeding just under the skin's surface. Small spots of bleeding under the skin are called purpura and larger spots are called ecchymoses. People with immune thrombocytopenia can have significant bleeding episodes, such as nose bleeds (epistaxis) or bleeding in the moist lining (mucosae) of the mouth. In severe cases, individuals may have gastrointestinal bleeding or blood in the urine or stool, or heavy and prolonged menstrual bleeding (menorrhagia). In very rare instances, bleeding inside the skull (intracranial hemorrhage) can occur, which can be life-threatening. A greater reduction in platelet numbers is often associated with more frequent bleeding episodes and an increased risk of severe bleeding.While immune thrombocytopenia can be diagnosed at any age, there are two periods when the condition is most likely to develop: early childhood and late adulthood. In children, the reduction in platelets is often sudden, but platelet levels usually return to normal levels within weeks to months. Immune thrombocytopenia in children is often preceded by a minor infection, such as an upper respiratory infection, but the relationship between the infection and immune thrombocytopenia is not clear. In adults, the development of immune thrombocytopenia is usually gradual and the condition tends to persist throughout life.
X-linked hyper IgM syndrome (HIGM1), a disorder of abnormal T- and B-cell function, is characterized by low serum concentrations of IgG and IgA and normal or elevated serum concentrations of IgM. Mitogen proliferation may be normal, but NK- and T-cell cytotoxicity are frequently impaired. Antigen-specific responses may be decreased or absent. The range of clinical findings varies, even within the same family. More than 50% of males with HIGM1 develop symptoms by age one year, and more than 90% are symptomatic by age four years. HIGM1 usually presents in infancy with recurrent upper- and lower-respiratory tract bacterial infections, opportunistic infections, and recurrent or protracted diarrhea associated with failure to thrive. Neutropenia, thrombocytopenia, and anemia are common. Autoimmune and/or inflammatory disorders, such as sclerosing cholangitis, have been reported. Significant neurologic complications, often the result of a CNS infection, are seen in 10%-15% of affected males. Liver disease, including primary cirrhosis and carcinomas (bile duct carcinomas, hepatocellular carcinomas, adenocarcinomas of the liver and gall bladder), and tumors of the gastrointestinal tract (carcinoid of the pancreas, glucagonoma of the pancreas) are common life-threatening complications in adolescents and young adults with HIGM1. Affected males are also at an increased risk for lymphoma, particularly Hodgkin's disease associated with Epstein-Barr virus infection.
Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often.Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA).During episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why some people with HIDS have high levels of IgD and IgA and some do not. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy.People with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, problems with movement and balance (ataxia), recurrent seizures (epilepsy), progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy.
A disorder that affects the production of complete immunoglobulins. Deletions in the heavy chain genes on chromosome 14 disrupt the synthesis and secretion of properly functioning antibodies resulting in monoclonal populations of truncated heavy chains without covalently bonded light chains. Such deletions have been implicated as playing a significant role in several diseases including leukemias, lymphomas and myelomas.
A rare dysgammaglobulinemia characterized by low or undetectable serum levels of immunoglobulin class E (IgE). It is an uncommon primary antibody deficiency. It is most likely an inherited immunodeficiency. It may be caused by decreased or inefficient class-switching from progenitor B cells without any corresponding decreases in the other isotypes. Most affected persons appear asymptomatic but may show a predisposition to autoimmune and respiratory diseases.
A rare dysgammaglobulinemia characterized by low or undetectable serum levels of immunoglobulin class D (IgD). It is an uncommon primary antibody deficiency. It is most likely an inherited immunodeficiency. It may be caused by decreased or inefficient production of IgD from progenitor B cells without any corresponding decreases in the other isotypes. Most affected persons are asymptomatic and do not appear to be at increased risk for infection.
Deficiency of secretory IgA (polymers of 2-4 IgA monomers are linked by two additional chains) and is the primary antibody response at the mucosal level, where it forms immune complexes with pathogens and allergens.
The presence of normal overall immunoglobulin levels with deficiency of specific immunoglobulins directed against a specific antigen or microorganism.
Leukocyte adhesion deficiency (LAD) is an autosomal recessive disorder of neutrophil function resulting from a deficiency of the beta-2 integrin subunit of the leukocyte cell adhesion molecule. The leukocyte cell adhesion molecule is present on the surface of peripheral blood mononuclear leukocytes and granulocytes and mediates cell-cell and cell-extracellular matrix adhesion. LAD is characterized by recurrent bacterial infections; impaired pus formation and wound healing; abnormalities of a wide variety of adhesion-dependent functions of granulocytes, monocytes, and lymphocytes; and a lack of beta-2/alpha-L, beta-2/alpha-M, and beta-2/alpha-X expression.
Congenital disorder of glycosylation type IIc (CDG2C) is an autosomal recessive disorder characterized by moderate to severe psychomotor retardation, mild dysmorphism, and impaired neutrophil motility. It is a member of a group of disorders with a defect in the processing of protein-bound glycans. For a general overview of congenital disorders of glycosylation (CDGs), see CDG1A (212065) and CDG2A (212066). The neutrophil defect in CDG2C has been referred to as 'leukocyte adhesion deficiency type II' (LAD2), which is a manifestation of the disorder; there are no cases of 'primary' LAD II (Frydman, 1996). Etzioni and Harlan (1999) provided a comprehensive review of both LAD1 (116920) and LAD2. While the functional neutrophil studies are similar in the 2 LADs, the clinical course is milder in LAD2. Furthermore, patients with LAD2 present other abnormal features, such as growth and mental retardation, which are related to the primary defect in fucose metabolism. Delayed separation of the umbilical cord occurs in LAD1.
Glutathione synthetase deficiency, or 5-oxoprolinuria, is an autosomal recessive disorder characterized, in its severe form, by massive urinary excretion of 5-oxoproline, metabolic acidosis, hemolytic anemia, and central nervous system damage. The metabolic defect results in decreased levels of cellular glutathione, which overstimulates the synthesis of gamma-glutamylcysteine and its subsequent conversion to 5-oxoproline (Larsson and Anderson, 2001).
Several documented cases of glutathione peroxidase (GPX1; 138320) deficiency in association with hemolytic anemia have been reported. However, Paglia (1989) stated: 'To date, no defects in glutathione peroxidase have been unequivocally incriminated in the pathogenesis of hemolytic syndromes, although several instances of partial deficiency have been reported in patients with anemias of unknown etiology. This association may be coincidental, since there is a broad range of ethnic variation in the erythrocyte enzyme' (Beutler and Matsumoto, 1975).
Complement factor D deficiency is an autosomal recessive immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway (summary by Biesma et al., 2001).
An autosomal recessive condition caused by mutation(s) in the CPN1 gene, encoding carboxypeptidase N catalytic chain. It may be characterized by episodic angioedema, chronic urticaria, asthma and/or allergic hypersensitivity.
Variable immunodeficiency with centromeric instability of chromosomes 1, 9, 16 and, less frequently, chromosome 2. Manifestations vary and most common symptoms include facial dysmorphism, mental retardation and prolonged respiratory, cutaneous, and gastrointestinal infections.
Nijmegen breakage syndrome (NBS) is characterized by progressive microcephaly, intrauterine growth retardation and short stature, recurrent sinopulmonary infections, an increased risk for cancer, and premature ovarian failure in females. Developmental milestones are attained at the usual time during the first year; however, borderline delays in development and hyperactivity may be observed in early childhood. Intellectual abilities tend to decline over time and most children tested after age seven years have mild to moderate intellectual disability. Recurrent pneumonia and bronchitis may result in respiratory failure and early death. Approximately 40% of affected individuals have developed malignancies before age 20 years, with the risk being highest for T-cell (55%) and B-cell lymphomas (45%). Other tumors include solid tumors (e.g., medulloblastoma, glioma, and rhabdomyosarcoma). Note, however, that much of what is reported about NBS is based on individuals who are homozygous for the single most common Eastern European pathogenic variant, c.657_661del5.
Congenital absence of the teeth; it may involve all (total anodontia) or only some of the teeth (partial anodontia, hypodontia), and both the deciduous and the permanent dentition, or only teeth of the permanent dentition. (Dorland, 27th ed)
Talon cusp is an accessory cusp located near the cingulum (the portion of the lingual or palatal aspect of the tooth that forms a convex protuberance at the cervical third of the anatomic crown).
Amelogenesis imperfecta is a disorder of tooth development. This condition causes teeth to be unusually small, discolored, pitted or grooved, and prone to rapid wear and breakage. Other dental abnormalities are also possible. These defects, which vary among affected individuals, can affect both primary (baby) teeth and permanent (adult) teeth.Researchers have described at least 14 forms of amelogenesis imperfecta. These types are distinguished by their specific dental abnormalities and by their pattern of inheritance. Additionally, amelogenesis imperfecta can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body.
Hypocalcified amelogenesis imperfecta is characterized by enamel of normal thickness on newly erupted and unerupted and unresolved teeth. The enamel is soft and may be lost soon after eruption leaving the crown composed only of dentin. The enamel has a cheesy consistency and can be scraped from the dentin. An anterior open bite has been recorded in over 60% of the cases observed. The hypocalcification type is the most frequent type of enamel dysplasia, occurring in about 1 in 20,000 individuals (Witkop and Sauk, 1976). Large masses of supragingival calculus become deposited on the teeth, and this is frequently associated with severe gingivitis or periodontitis (Winter and Brook, 1975).
Dentinogenesis imperfecta is a disorder of tooth development. This condition causes the teeth to be discolored (most often a blue-gray or yellow-brown color) and translucent. Teeth are also weaker than normal, making them prone to rapid wear, breakage, and loss. These problems can affect both primary (baby) teeth and permanent teeth.Researchers have described three types of dentinogenesis imperfecta with similar dental abnormalities. Type I occurs in people who have osteogenesis imperfecta, a genetic condition in which bones are brittle and easily broken. Dentinogenesis imperfecta type II and type III usually occur in people without other inherited disorders. A few older individuals with type II have had progressive high-frequency hearing loss in addition to dental abnormalities, but it is not known whether this hearing loss is related to dentinogenesis imperfecta.Some researchers believe that dentinogenesis imperfecta type II and type III, along with a condition called dentin dysplasia type II, are actually forms of a single disorder. The signs and symptoms of dentin dysplasia type II are very similar to those of dentinogenesis imperfecta. However, dentin dysplasia type II affects the primary teeth much more than the permanent teeth.
In dentin dysplasia type I, both primary and secondary dentitions are affected. The color and general morphology of the teeth are usually normal, although they may be slightly opalescent and blue or brown. Teeth may be very mobile and exfoliate spontaneously because of inadequate root formation. On radiographs, the roots are short and may be more pointed than normal. Pulp chambers are usually absent except for a chevron-shaped remnant in the crown (Witkop, 1975). Root canals are usually absent. Periapical radiolucencies may be present at the apices of affected teeth, for reasons unknown. On light microscopic examination of the permanent teeth, the coronal dentin is normal, but further apically becomes irregular, fills the pulp chamber, and has a 'sand-dune' morphology. Scanning electron microscopic studies of the deciduous and permanent teeth have been reported (Sauk et al., 1972; Melnick et al., 1980). Subclassification of Dentin Dysplasia Type I O Carroll et al. (1991) and O Carroll and Duncan (1994) reviewed dentin dysplasia and proposed 4 subtypes of dentin dysplasia type I, which they designated as DD1a-d. In DD1a, there is complete obliteration of pulp chambers and no root development, with many periapical radiolucent areas. In DD1b, there are horizontal crescent-shaped radiolucent pulpal remnants and a few millimeters of root development, with many periapical radiolucent areas. DD1c shows 2 horizontal crescent-shaped radiolucent lines and significant but incomplete root development, with or without periapical radiolucent areas. DD1d is characterized by visible pulp chambers and oval pulp stones in the coronal third of the root canal with bulging of the root around the stones and few if any periapical radiolucent areas. The authors noted that the distinctions between the subtypes of DD1 were primarily useful clinically in terms of treatment options.
Dentin dysplasia type II is a defect of dentin formation in which the clinical appearance of the secondary teeth is normal, but the primary teeth may appear opalescent, similar to teeth affected by dentinogenesis imperfecta. The roots of the teeth are of normal shape and morphologic character. The pulp chambers and root canals of the anterior teeth and the premolars are shaped like thistle tubes because of the radicular extension of the pulp chamber. Most teeth show accumulations of pulp stones in these unusually shaped pulp chambers (summary by Kalk et al., 1998). Also see dentin dysplasia type I (DTDP1; 125400).
Development of hard tissue in the inner substance of the tooth where blood vessels, lymphatic, and nerve tissue is normally found.
Overgrowth of the gingival tissue caused by phenytoin, cyclosporine A, and calcium channel blockers.
Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva (summary by Hart et al., 2002). Genetic Heterogeneity of Hereditary Gingival Fibromatosis Other loci for gingival fibromatosis have been mapped to chromosome 5q (GINGF2; 605544), chromosome 2p23.3-p22.3 (GINGF3; 609955), and chromosome 11p15 (GINGF4; 611010). GINGF5 (617626) is caused by mutation in the REST gene (600571) on chromosome 4q12. There is some evidence for a locus on chromosome 2p16-p13 (see MAPPING).
A non-neoplastic nodular lesion that arises from the gingiva. It is composed of epithelial cells lining connective tissue stroma.
Loss of the superficial layer of the oral mucosa usually resulting in a shallow or crusted lesion.
A clinical term that indicates the presence of a white patch on the buccal mucosa in the mouth which cannot be characterized as any other disease. It may be a precancerous condition and in most cases histologic examination reveals keratosis.
Non-homogenous leukoplakia on the oral mucosa. It is associated with a high risk for malignant transformation.
Warty leukoplakia on the oral mucosa. It is associated with a high risk for malignant transformation.
A premalignant pathologic process that affects the oral mucosa. It is associated with the use of smoked tobacco. It appears as white lesions on the oral mucosa. Morphologically it is characterized by the pathologic production of keratin in the mucosal epithelial surface with or without epithelial atypia. It may reverse with the cessation of tobacco use.
Increased pigmentation, either focal or generalized, of the mucosa of the mouth. [pmid:19125428]
A condition characterized by persistent or recurrent labial enlargement, ORAL ULCER, and other orofacial manifestations in the absence of identifiable CROHN DISEASE; or SARCOIDOSIS. Among experts there is disagreement on whether orofacial granulomatosis is a distinct clinical disorder or an initial presentation of Crohn disease.
Lack of symmetry between the left and right mandible.
Asymmetry between the left and right sides of the maxilla.
Malocclusion in which the mandible and maxilla are anteroposteriorly normal as reflected by the relationship of the first permanent molar (i.e., in neutroclusion), but in which individual teeth are abnormally related to each other.
Increased distance between the maxillary anterior teeth and the mandibular anterior teeth in the anterior-posterior axis.
Abnormal prominence of the chin related to increased length of the mandible.
A clinical term that indicates the presence of a white patch on the surface of the lip which cannot be characterized as any other disease. It may be a precancerous condition and in most cases histologic examination reveals keratosis.
A depression located at an oral commissure.
A condition characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. This syndrome was first described in 1980 by Read and associates. Subtypes include COLLAGENOUS COLITIS and LYMPHOCYTIC COLITIS. Both have similar clinical symptoms and are distinguishable only by histology.
A subtype of MICROSCOPIC COLITIS, characterized by chronic watery DIARRHEA of unknown origin, a normal COLONOSCOPY but abnormal histopathology on BIOPSY. Microscopic examination of biopsy samples taken from the COLON show infiltration of LYMPHOCYTES in the superficial EPITHELIUM and the underlying connective tissue (lamina propria).
A circumscribed inflammatory and necrotic erosive lesion in the mucosa surface of the rectum.
Acute hepatitis D infection in carrier person with chronic hepatitis B virus infection.
A non-neoplastic or neoplastic vascular disorder that affects the liver. Representative examples include veno-occlusive disease, hemangioma, lymphangioma, and angiosarcoma.
A term referring to fatty replacement of the hepatic parenchyma which is not related to alcohol use.
Blockage in the biliary tract that carries bile from the liver to the gallbladder and small intestine. Causes include gallstones, biliary tract strictures and inflammation, pancreatitis, cirrhosis, lymph node enlargement, and bile duct and pancreas neoplasms.
The presence of cyst of the intrahepatic bile duct.
The leakage of bile into the abdominal cavity as a result of injury to the bile duct.
Leakage of bile due to breakdown of a biliary anastomosis.
Constipation of sudden onset and lasting for less than three months.
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Nephrotic syndrome, occurring in the pediatric population, characterized by the normalization of proteinuria with the administration of corticosteroids.
A form of nephrotic syndrome that does not respond to treatment with steroid medication.
Nephrotic syndrome characterized by two or more consecutive relapses during steroid tapering or within fourteen days of discontinuing steroids.
The nephrotic syndrome is characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. Approximately 20% of affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure (summary by Fuchshuber et al., 1996). Nephrotic syndrome type 1 (NPHS1) is characterized by prenatal onset of massive proteinuria followed by severe steroid-resistant nephrotic syndrome apparent at birth with rapid progression to end-stage renal failure (Kestila et al., 1998). Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (see NOMENCLATURE section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. Genetic Heterogeneity of Nephrotic Syndrome and Focal Segmental Glomerulosclerosis Nephrotic syndrome and FSGS are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also NPHS2 (600995), caused by mutation in the podocin gene (604766); NPHS3 (610725), caused by mutation in the PLCE1 gene (608414); NPHS4 (256370), caused by mutation in the WT1 gene (607102); NPHS5 (614199), caused by mutation in the LAMB2 gene (150325); NPHS6 (614196), caused by mutation in the PTPRO gene (600579); NPHS7 (615008), caused by mutation in the DGKE gene (601440); NPHS8 (615244), caused by mutation in the ARHGDIA gene (601925); NPHS9 (615573), caused by mutation in the COQ8B gene (615567); NPHS10 (615861), caused by mutation in the EMP2 gene (602334); NPHS11 (616730), caused by mutation in the NUP107 gene (607617); NPHS12 (616892), caused by mutation in the NUP93 gene (614351); NPHS13 (616893), caused by mutation in the NUP205 gene (614352); NPHS14 (617575), caused by mutation in the SGPL1 gene (603729); NPHS15 (617609), caused by mutation in the MAGI2 gene (606382); NPHS16 (617783), caused by mutation in the KANK2 gene (614610), NPHS17 (618176), caused by mutation in the NUP85 gene (170285); NPHS18 (618177), caused by mutation in the NUP133 gene (607613); and NPHS19 (618178), caused by mutation in the NUP160 gene (607614). FSGS1 (603278) is caused by mutation in the ACTN4 gene (604638) and FSGS2 (603965) by mutation in the TRPC6 gene (603652). FSGS3 (607832) is associated with variation in the CD2AP gene (604241). FSGS4 (612551) has been mapped to chromosome 22q12, and FSGS5 (613237) is caused by mutation in the INF2 gene (610982).
Inflammation of the glomeruli status post infection with nephritogenic streptococci, most often group A beta hemolytic streptococcus.
A histopathologic term for a pattern of diseases characterized by extensive crescent formation in the glomeruli; patients present clinically with rapid deterioration of renal function, and possible progression to end-stage renal failure within weeks or months.
An autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and characteristic inclusions in peripheral blood leukocytes, with the additional features of nephritis, hearing loss, and eye abnormalities, mostly cataracts; it is associated with mutation of the MYH9 gene.
Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)
Acute kidney injury caused by ischemic necrosis of the renal cortex.
The presence of microscopic crystalline calcium precipitates in the form of oxalate and/or phosphate in the renal parenchyma.
The deposition of calcium salts in the parenchyma of the renal cortex (the outer portion of the kidney between the renal capsule and the renal medulla).
The deposition of calcium salts in the parenchyma of the renal medulla (innermost part of the kidney).
An autoimmune disease of the KIDNEY and the LUNG. It is characterized by the presence of circulating autoantibodies targeting the epitopes in the non-collagenous domains of COLLAGEN TYPE IV in the basement membranes of kidney glomeruli (KIDNEY GLOMERULUS) and lung alveoli (PULMONARY ALVEOLI), and the subsequent destruction of these basement membranes. Clinical features include pulmonary alveolar hemorrhage and glomerulonephritis.
Mesangial sclerosis of the kidneys and eye abnormalities originally reported in a sister and brother, who also suffered from psychomotor retardation, both of whom died in early childhood.
Renal tubular acidosis with deafness is a disorder characterized by kidney (renal) problems and hearing loss. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with this disorder, the kidneys do not remove enough acidic compounds from the body. Instead, the acids are absorbed back into the bloodstream, and the blood becomes too acidic. This chemical imbalance, called metabolic acidosis, can result in a range of signs and symptoms that vary in severity. Metabolic acidosis often causes nausea, vomiting, and dehydration; affected infants tend to have problems feeding and gaining weight (failure to thrive). Most children and adults with renal tubular acidosis with deafness have short stature, and many develop kidney stones.The metabolic acidosis that occurs in renal tubular acidosis with deafness may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. Rarely, people with renal tubular acidosis with deafness have episodes of hypokalemic paralysis, a condition that causes extreme muscle weakness associated with low levels of potassium in the blood (hypokalemia).In people with renal tubular acidosis with deafness, hearing loss caused by changes in the inner ear (sensorineural hearing loss) usually begins between childhood and young adulthood, and gradually gets worse. An inner ear abnormality affecting both ears occurs in most people with this disorder. This feature, which is called enlarged vestibular aqueduct, can be seen with medical imaging. The vestibular aqueduct is a bony canal that runs from the inner ear into the temporal bone of the skull and toward the brain. The relationship between enlarged vestibular aqueduct and hearing loss is unclear. In renal tubular acidosis with deafness, enlarged vestibular aqueduct typically occurs in individuals whose hearing loss begins in childhood.
Urofacial syndrome (UFS) is characterized by prenatal or infantile onset of urinary bladder voiding dysfunction, abnormal facial movement with expression (resulting from abnormal co-contraction of the corners of the mouth and eyes), and often bowel dysfunction (constipation and/or encopresis). Bladder voiding dysfunction increases the risk for urinary incontinence, megacystis, vesicoureteric reflux, hydroureteronephrosis, urosepsis, and progressive renal impairment. In rare instances, an individual who has (a) a molecularly confirmed diagnosis and/or (b) an affected relative meeting clinical diagnostic criteria manifests only the characteristic facial features or only the urinary bladder voiding dysfunction (not both). Nocturnal lagophthalmos (incomplete closing of the eyes during sleep) appears to be a common and significant finding.
Glomerulopathy with fibronectin deposits (GFND) is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Pathologic examination shows enlarged glomeruli with mesangial and subendothelial fibrillary deposits that show strong immunoreactivity to fibronectin (FN1; 135600) (Castelletti et al., 2008). Genetic Heterogeneity of Glomerulopathy with Fibronectin Deposits The GFND1 locus maps to chromosome 1q32. See also GFND2 (601894), which is caused by mutation in the FN1 gene (135600) on chromosome 2q35.
A complication occurring during hemodialysis that is thought to be due to a rapid decrease in blood urea nitrogen, and is characterized by an increase in intracranial pressure resulting in nausea, headache, vomiting, restlessness, and/or a decreased level of consciousness.
Gradual loss of donor kidney function occurring months to years after transplantation. It is characterized by renal tubular atrophy, interstitial fibrosis, and arterial wall thickening.
A non-neoplastic or neoplastic disorder affecting the ureter.
An inflammation of the bladder which is not caused by an infection of the urinary tract. Representative examples include interstitial cystitis and radiation-induced cystitis.
Nephrolithiasis in which the composition of the stone(s) is predominantly uric acid.
X-linked recessive nephrolithiasis with renal failure is a form of X-linked hypercalciuric nephrolithiasis, which comprises a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrolithiasis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009.
Circinate Balanitis: a cutaneous finding of Reiter's syndrome, which in uncircumcised males has the appearance of a moist superficial erosion on the glans penis particularly around the urethral meatus. Lesions may also occur on the corona and shaft. In circumcised males comparable lesions occur on the glans or corona but are often characterized as hyperkeratotic papules or superficial erosions. Characteristically in Reiter's syndrome these lesions are painless.
Spermatogenic arrest during meiosis is a cause of infertility. The histologic picture of meiotic arrest is rather constant. Meiotic arrest is characterized by germ cells that enter meiosis and undergo the first chromosomal reduction from 4n to 2n but are then unable to proceed further. This results in tubules containing spermatocytes as the latest developmental stage of germ cells. Meiotically arrested spermatocytes accumulate in the tubules, degenerate, and are easily distinguishable from normal spermatocytes by their partially condensed chromosomes. Although the cause of infertility in patients with meiotic arrest often remains unidentified, this histologic picture can be observed in patients with nonidiopathic infertility as well, such as in the case of microdeletions of the Y chromosome, chromosomal abnormalities, and cryptorchidism, suggesting that different causal factors can result in the same effect (summary by Luetjens et al., 2004). Genetic Heterogeneity of Spermatogenic Failure SPGF1 represents an autosomal recessive form of spermatogenic failure associated with defects in meiosis. Also see SPGF2 (108420), associated with rearrangements on chromosome 1; SPGF3 (606766), caused by mutation in the SLC26A8 gene (608480) on chromosome 6p21; SPGF4 (270960), caused by mutation in the SYCP3 gene (604759) on chromosome 12q23; SPGF5 (243060), caused by mutation in the AURKC gene (603495) on chromosome 19q13; SPGF6 (102530), caused by mutation in the SPATA16 gene (609856) on chromosome 3q26; SPGF7 (612997), caused by mutation in the CATSPER gene (606389) on chromosome 11q13; SPGF8 (613957), caused by mutation in the NR5A1 gene (184757) on chromosome 9q33; SPGF9 (613958), caused by mutation in the DPY19L2 gene (613893) on chromosome 12q14; SPGF10 (614822), caused by mutation in the SEPT12 gene (611562) on chromosome 16p13; SPGF11 (615081), caused by mutation in the KLHL10 gene (608778) on chromosome 17p21; SPGF12 (615413), caused by mutation in the NANOS1 gene (608226) on chromosome 10q26; SPGF13 (615841), caused by mutation in the TAF4B gene (601689) on chromosome 18q11; SPGF14 (615842), caused by mutation in the ZMYND15 gene (614312) on chromosome 17p13; SPGF15 (616950), caused by mutation in the SYCE1 gene (611486) on chromosome 10q26; SPGF16 (617187), caused by mutation in the SUN5 gene (613942) on chromosome 20q11; SPGF17 (617214), caused by mutation in the PLCZ1 gene (608075) on chromosome 12p12; SPGF18 (617576), caused by mutation in the DNAH1 gene (603332) on chromosome 3p21; SPGF19 (617592), caused by mutation in the CFAP43 gene (617558) on chromosome 10q25; SPGF20 (617593), caused by mutation in the CFAP44 gene (617559) on chromosome 3q13; SPGF21 (617644), caused by mutation in the BRDT gene (602144) on chromosome 1p22; SPGF22 (617706), caused by mutation in the MEIOB gene (617670) on chromosome 16p13; SPGF23 (617707), caused by mutation in the TEX14 gene (605792) on chromosome 17q22; SPGF24 (617959), caused by mutation in the CFAP69 gene (617949) on chromosome 7q21; SPGF25 (617960), caused by mutation in the TEX15 gene (605795) on chromosome 8p12; SPGF26 (617961), caused by mutation in the TSGA10 gene (607166) on chromosome 2q11; SPGF27 (617965), caused by mutation in the AK7 gene (615364) on chromosome 14q32; SPGF28 (618086), caused by mutation in the FANCM gene (609644) on chromosome 14q21; SPGF29 (618091), caused by mutation in the SPINK2 gene (605753) on chromosome 4q12; SPGF30 (618110), caused by mutation in the TDRD9 gene (617963) on chromosome 14q32; SPGF31 (618112), caused by mutation in the PMFBP1 gene (618085) on chromosome 16q22; SPGF32 (618115), caused by mutation in the SOHLH1 gene (610224) on chromosome 9q34; SPGF33 (618152), caused by mutation in the WDR66 gene (618146) on chromosome 12q24; SPGF34 (618153), caused by mutation in the FSIP2 gene (615796) on chromosome 2q32; and SPGF35, caused by mutation in the QRICH2 gene (618304) on chromosome 17q25. X-linked forms of spermatogenic failure include SPGFX1 (305700) and SPGFX2 (309120). Y-linked forms of spermatogenic failure include SPGFY1 (400042) and SPGFY2 (415000). Spermatogenic failure can also result from underlying endocrinologic disorders (see, e.g., hypogonadotropic hypogonadism, 146110) or ciliary dyskinesias (see, e.g., CILD1, 244400).
Spermatogenic failure-5 is a form of male infertility associated with large-headed, multiflagellar, polyploid spermatozoa (Dieterich et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Testicular failure, the cause of which is not present at birth.
A condition in which the percentage of motile sperm is abnormally low.
Spermatogenic failure-6 is a form of male infertility with globozoospermia. The acrosome is a unique structure of the mature spermatozoon, which plays an important role at the site of sperm-zonapellucida binding during the fertilization process. Globozoospermia (also called round-headed spermatozoa) is a human infertility syndrome caused by spermatogenesis defects (Lalonde et al., 1988, Singh, 1992). The most prominent feature of globozoospermia is the malformation of the acrosome and, in the most severe cases, the acrosome is totally absent. Globozoospermia is also characterized by abnormal nuclear shape as well as abnormal arrangement of the mitochondria of the spermatozoon (Battaglia et al., 1997). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
An infectious process affecting the vagina. Symptoms include pain and purulent discharge.
An indication that the anogenital distance is less than the norm.
Increased chance of harm during the gestational period of the formation of an offspring / child
A multiple pregnancy that over time is spontaneously reduced by one or more embryos which are then resorbed.
A rare type of abnormal pregnancy in which EMBRYO IMPLANTATION occurs at a lateral angle of the UTERUS, medial to the uterotubal junction and the ROUND LIGAMENT OF UTERUS.
Endometritis that develops following an abortion.
A condition in which the placenta implants abnormally into the uterine myometrium, rather than implanting into the uterine decidua basalis as is normal.
A complication of pregnancy and delivery in which the umbilical cord wraps around the fetal neck once or multiple times.
Death resulting from conditions or complications which are unique to pregnancy and occur during the antepartum, intrapartum, or postpartum period.
A rare, benign, inflammatory breast disease occurring in premenopausal women shortly after a recent pregnancy. The origin is unknown but it is commonly mistaken for malignancy and sometimes associated with BREAST FEEDING and the use of ORAL CONTRACEPTIVES.
Familial juvenile hypertrophy of the breast (JHB) is a rare condition characterized by gigantomastia in peripubertal females. The pathology is limited to the breast with otherwise normal growth and development (summary by Genzer-Nir et al., 2010). A syndrome has been described in which affected females display JHB in association with onychodystrophy/anonychia and abnormalities of the distal phalanges (ODP; see 106995), whereas males have only ODP (mammary-digital-nail syndrome; 613689).
Insufficient production of steroid hormones (primarily cortisol) by the adrenal glands as a result of a primary defect in the glands themselves.
An infection involving the surface of the skin and subcutaneous tissues in a defined area of the body.
Hereditary polymorphic light eruption is a form of photosensitivity found in the American Indians of the central plains of Canada and the United States and in the Indians of Central and South America. The disorder has also been called familial actinic prurigo, solar dermatitis, and hydroa aestivale. In northern latitudes, skin lesions appear on exposed areas early in spring, become severe during the summer, and abate in the fall. Usually the disorder appears in childhood with eczematous crusted eruptions on the face and arms. Fissured, crusted exudative cheilitis develops on the lips, especially the lower lip. The dorsum of the hands, the laterodorsal aspects of the forearms, and the lower half of the arms often show excoriated papular and nodular lesions. Children frequently have complicating pyoderma. Adults usually exhibit an erythematous plaquelike eruption on the face and other exposed areas. The disease is more severe in children than in adults. Glomerulonephritis can follow streptococcal pyoderma (summary by Fusaro and Johnson, 1980).
A dermatosis with pruritic sterile papules and pustules that come together to form plaques with papulovesicular borders, and a tendency toward central clearing and hyperpigmentation, with spontaneous exacerbations and remissions. Histologically variable with folliculitis of follicle sheath and perifollicular dermis and spongiosis of follicular epithelium, sometimes with peripheral leukocytosis and or eosinophilia and or eosinophilic abscesses.
A rare variant of cutaneous lichen planus with the presence of hyperpigmented lichenoid lesions in sun-exposed or flexural areas of the body. A rare disease in Europe but it is common in Indian populations and in the Middle East. The overall prevalence is unknown. There is no difference in distribution between males and females. The disease usually appears in the third and fourth decade of life. The lesions are asymptomatic or mildly pruritic. Skin changes are dark brown or slate grey macules or papules with, in most cases, a diffuse pigmentation pattern. They most commonly affect the face, neck and upper limbs. Cause is unknown but various factors (e.g. viral infections and certain topical agents including mustard oil and henna hair dyes) can trigger the disease.
Inward advance of skin over the nail plate.
Benign childhood alopecia that improves spontaneously with aging. It is characterized by anagen hairs (misshapen hair bulbs and absent inner and outer root sheaths), thin, and sparse hairs that pulls out easily.
A type of acne in which open and closed comedones comprise the majority of the lesions, with substantially fewer papules and pustules.
A decrease in lower leg circumference due to recurrent ulceration and fat necrosis causing loss of subcutaneous tissue in a patient with venous stasis disease
Dermatoid drug eruption characterized by widespread erythematous macules and papules often associated with a mild fever and itch.
Kindler syndrome (KS), a rare subtype of inherited epidermolysis bullosa, is characterized by skin fragility and acral blister formation beginning at birth, diffuse cutaneous atrophy, photosensitivity (which is most prominent during childhood and usually decreases after adolescence), poikiloderma, diffuse palmoplantar hyperkeratosis, and pseudosyndactyly. Mucosal manifestations are also common and include hemorrhagic mucositis and gingivitis, periodontal disease, premature loss of teeth, and labial leukokeratosis. Other mucosal findings can include ectropion, esophageal strictures/stenosis, anal stenosis, colitis, urethral stenosis/strictures, and severe phimosis. Severe long-term complications of KS include periodontitis, mucosal strictures, and aggressive squamous cell carcinomas. Manifestations can range from mild to severe.
A rare syndrome that presents with recurrent aphthous ulcers and relapsing polychondritis, and often but not always is accompanied by the features of Behcet's syndrome, which include genital ulcers and uveitis.
A poorly circumscribed, intermediate fibrocytic neoplasm arising from the superficial soft tissues. It is characterized by the presence of spindle-shaped fibroblasts, and an infiltrative growth pattern.
Restrictive dermopathy is a rare, lethal genodermatosis with characteristic manifestations that are easily recognizable at birth: thin, tightly adherent translucent skin with erosions at flexure sites, superficial vessels, typical facial dysmorphism, and generalized joint ankylosis. Prenatal signs can include intrauterine growth retardation, reduced fetal movements, polyhydramnios, and premature rupture of the membranes. Most infants die within the first week of life (summary by Smigiel et al., 2010).
Wiedemann-Rautenstrauch syndrome (WDRTS) is a rare autosomal recessive neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, a progeroid appearance, hypotonia, and variable mental impairment (summary by Toriello, 1990). Average survival in WDRTS is 7 months, although survival into the third decade of life has been reported (Akawi et al., 2013).
A neoplastic process characterized by a diffuse poorly circumscribed overgrowth of adipose tissue in the pelvic region. Clinical presentation includes complaints of back and abdominal pain, urinary frequency, perineal pain and constipation. It predominately affects black males.
Encephalocraniocutaneous lipomatosis (ECCL) is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system (CNS) anomalies (Moog et al., 2007). The malformations in ECCL are patchy and asymmetric. The most characteristic skin anomaly is nevus psiloliparus, a well-demarcated, alopecic fatty tissue nevus on the scalp, seen in 80% of affected individuals. Other dermatologic features include frontotemporal or zygomatic subcutaneous fatty lipomas, non-scarring alopecia, focal dermal hypoplasia or aplasia of the scalp, periocular skin tags, and pigmentary abnormalities following the lines of Blaschko. Choristomas of the eye (epibulbar dermoids or lipodermoids) are also present in 80% of patients, and can be unilateral or bilateral. Characteristic CNS features in ECCL include intracranial and intraspinal lipomas, seen in 61% of patients, and less often cerebral asymmetry, arachnoid cysts, enlarged ventricles, and leptomeningeal angiomatosis. A predisposition to low-grade gliomas has also been observed. Seizures and intellectual disability are common, but one-third of affected individuals have normal intellect. Skeletal manifestations include bone cysts and jaw tumors, such as odontomas, osteomas, and ossifying fibromas (summary by Bennett et al., 2016).
A dermatologic manifestation of lupus involving edematous papules and plaques that are typically found on sun-exposed areas of the body. It most often resolves without scarring or pigmentation changes.
Autoimmune disease characterized by subepidermal blisters and linear deposition of autoantibodies at the dermoepidermal junction. The accumulated autoantibodies are of IMMUNOGLOBULIN A and occasionally IMMUNOGLOBULIN G classes against epidermal BASEMENT MEMBRANE proteins. The dermatosis is sometimes associated with malignancies and use of certain drugs (e.g., VANCOMYCIN).
Complex pain syndrome with unknown etiology, characterized by constant or intermittent generalized vulva pain (Generalized vulvodynia) or localized burning sensations in the VESTIBULE area when pressure is applied (Vestibulodynia, or Vulvar Vestibulitis Syndrome). Typically, vulvar tissue with vulvodynia appears normal without infection or skin disease. Vulvodynia impacts negatively on a woman's quality of life as it interferes with sexual and daily activities.
A rare autosomal recessive disorder characterized by developmental abnormalities of the skin, sweat glands, hair and nails. Patients have a reduced ability to sweat. Other signs and symptoms include hypotrichosis and teeth malformations.
Ectrodactyly of the hands and feet (lobster claw anomaly), nasolacrimal duct obstruction, cleft lip and palate, and urogenital abnormalities are the cardinal features. Mental retardation, conductive hearing loss, and abnormalities of the ears and face are occasionally associated. The phenotype overlaps in parts that of the ectrodactyly-mandibulo-facial dysostosis syndrome.
Complete congenital absence of dermatoglyphs is a rare syndrome characterized by autosomal dominant inheritance of the lack of ridges on palms and soles, neonatal acral blisters and facial milia, adult traumatic blistering and fissuring, absent or reduced sweating of palms and soles, and contracture of digits. Additional features may include single palmar transverse crease, palmoplantar keratoderma, and nail grooving (summary by Limova et al., 1993).
The TP63-related disorders comprise six overlapping phenotypes: Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome (which includes Rapp-Hodgkin syndrome). Acro-dermo-ungual-lacrimal-tooth (ADULT) syndrome. Ectrodactyly, ectodermal dysplasia, cleft lip/palate syndrome 3 (EEC3). Limb-mammary syndrome. Split-hand/foot malformation type 4 (SHFM4). Isolated cleft lip/cleft palate (orofacial cleft 8). Individuals typically have varying combinations of ectodermal dysplasia (subjective hypohidrosis, nail dysplasia, sparse hair, tooth abnormalities), cleft lip/palate, split-hand/foot malformation/syndactyly, lacrimal duct obstruction, hypopigmentation, and hypoplastic breasts and/or nipples. Findings associated with a single phenotype include ankyloblepharon filiforme adnatum (tissue strands that completely or partially fuse the upper and lower eyelids), skin erosions especially on the scalp associated with areas of scarring and alopecia, hypospadias, trismus, and excessive freckling.
GAPO syndrome is the acronymic designation for a complex of growth retardation, alopecia, pseudoanodontia (failure of tooth eruption), and progressive optic atrophy (Tipton and Gorlin, 1984). Ilker et al. (1999) and Bayram et al. (2014) noted that optic atrophy is not a consistent feature of the disorder.
A form of ectodermal dysplasia characterized by defects of the skin and skin appendages in association with mental retardation, short stature, hypotrichosis, hypodontia, and other defects.
CHAND syndrome is characterized by ankyloblepharon, sparse, curly, and woolly hair, nail dysplasia, and oral frenula (summary by Busa et al., 2017).
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Witkop syndrome is a rare autosomal dominant ectodermal dysplasia involving the teeth and nails. Although a few reported cases have sparse or fine hair, almost all affected individuals have normal hair, sweat glands, and ability to tolerate heat. Affected individuals have a variable number and variable types of congenitally missing permanent and/or primary teeth, which frequently results in lip eversion due to loss of occlusion in the vertical dimension. Nails are generally thin, slow-growing, brittle, and spoon-shaped (koilonychia). Toenails are usually more severely affected than fingernails. The nail defects are alleviated with age and may not be easily detectable during adulthood (summary by Jumlongras et al., 2001).
Kohlschutter-Tonz syndrome is an autosomal recessive disorder characterized by severe global developmental delay, early-onset intractable seizures, spasticity, and amelogenesis imperfecta affecting both primary and secondary teeth and causing yellow or brown discoloration of the teeth. Although the phenotype is consistent, there is variability. Intellectual disability is related to the severity of seizures, and the disorder can thus be considered an epileptic encephalopathy. Some infants show normal development until seizure onset, whereas others are delayed from birth. The most severely affected individuals have profound mental retardation, never acquire speech, and become bedridden early in life (summary by Schossig et al., 2012 and Mory et al., 2012).
Keratolytic winter erythema, also known as Oudtshoorn skin disease, manifests during childhood with recurrent episodes of palmoplantar erythema and centrifugal epidermal peeling. Lateral and dorsal aspects of the hands and feet can be involved. A less common finding is a slowly migratory, annular erythema that is seen mostly on the extremities. Between flares, the skin may appear unremarkable. Hyperhidrosis, associated with a pungent odor, is invariably present, and itching can occur. Peeling is preceded by the formation of dry blisters due to keratolysis, whereas formation of vesicles or bullae is rare. Cold weather, moisture, febrile diseases, and physical and mental stress can trigger exacerbations. In severely affected individuals, skin manifestations persist unremittingly. Penetrance of the disease is high, but expressivity is variable, even within the same family (summary by Ngcungcu et al., 2017).
A hereditary syndrome this is characterized by palmoplantar keratoderma accompanied by leukoplakia and may be associated with a high lifetime risk of esophageal cancer, as seen in Howel-Evans Syndrome.
Huriez syndrome (HRZ) is characterized by the triad of congenital scleroatrophy of the distal extremities, palmoplantar keratoderma, and hypoplastic nail changes. The development of aggressive squamous cell carcinoma (SCC) in areas of affected skin is a distinctive feature of the syndrome, occurring in approximately 15% of patients. HRZ-associated SCC shows early onset, mostly in the third to fourth decades of life, and early metastasis formation (summary by Lee et al., 2000). See also 610644 for description of a disorder resembling Huriez syndrome, involving palmoplantar hyperkeratosis and squamous cell carcinoma in association with SRY (480000)-negative female-to-male XX sex reversal, caused by mutation in the RSPO1 gene (609595).
Dyschromatosis symmetrica hereditaria (DSH), also called symmetric dyschromatosis of the extremities and symmetric or reticulate acropigmentation of Dohi (Komaya, 1924), is characterized by hyperpigmented and hypopigmented macules on the face and dorsal aspects of the extremities that appear in infancy or early childhood. DSH generally shows an autosomal dominant pattern of inheritance with high penetrance. The condition has been reported predominantly in Japanese and Chinese individuals. Review of Reticulate Pigment Disorders Muller et al. (2012) reviewed the spectrum of reticulate pigment disorders of the skin, tabulating all reported cases of patients with Dowling-Degos disease (see DDD1; 179850), reticulate acropigmentation of Kitamura (RAK; 615537), reticulate acropigmentation of Dohi (RAD), Galli-Galli disease (GGD), and Haber syndrome (HS). Of 82 cases, 26 (31.7%) were clinically diagnosed as DDD, 13 (15.9%) as RAD, 11 (13.4%) as GGD, 8 (9.8%) as RAK, and 8 (9.8%) as HS; in addition, 16 (19.5%) of the cases showed overlap between DDD and RAK. Muller et al. (2012) also published photographs of an affected individual exhibiting an overlap of clinical features of DDD, GGD, RAD, and RAK. The authors noted that in reticulate disorders of the skin, the main disease entity is DDD, with a subset of cases exhibiting acantholysis (GGD), facial erythema (HS), or an acral distribution (RAD; RAK). Muller et al. (2012) concluded that all reticulate pigment diseases of the skin are varying manifestations of a single entity. Genetic Heterogeneity of Reticulate Pigment Disorders For a discussion of genetic heterogeneity of reticulate pigment disorders, see 179850.
Dermatopathia pigmentosa reticularis is a rare heritable disorder consisting of a triad of cutaneous findings including reticulate hyperpigmentation, noncicatricial alopecia, and onychodystrophy. Variable features include adermatoglyphia, hypohidrosis or hyperhidrosis, and palmoplantar hyperkeratosis (Heimer et al., 1992).
A benign, self-limited eruption of vesicles, pustules and macules seen in newborns. The fluid-filled lesions typically rupture and resolve within 48 hours while the macular lesions may persist for months.
A rare, congenital skin lesion consisting of a proliferation of eccrine glands with a vascular stroma. It presents as a flesh-colored, hyperhidrotic, painful papule or plaque appearing at birth or during childhood.
A benign adnexal neoplasm occurring during childhood or adolescence. It usually presents as a papular lesion or a plaque on the head and neck. It may arise in an organoid nevus such as sebaceous. It is characterized by an endophytic invagination of the epithelium into the dermis. There are dermal cystic spaces present, containing villous projections. Complete excision is curative.
A type of pilosebaceous hamartoma characterized by the development of a linear, flesh colored, fine papular eruption on the head, neck and upper chest after puberty.
Carney complex (CNC) is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas. Pale brown to black lentigines are the most common presenting feature of CNC and typically increase in number at puberty. Cardiac myxomas occur at a young age, may occur in any or all cardiac chambers, and can manifest as intracardiac obstruction of blood flow, embolic phenomenon, and/or heart failure. Other sites for myxomas include the skin, breast, oropharynx, and female genital tract. Primary pigmented nodular adrenocortical disease (PPNAD), which causes Cushing syndrome, is the most frequently observed endocrine tumor in CNC, occurring in approximately 25% of affected individuals. Large-cell calcifying Sertoli cell tumors (LCCSCTs) are observed in one third of affected males within the first decade and in most adult males. Up to 75% of individuals with CNC have multiple thyroid nodules, most of which are nonfunctioning thyroid follicular adenomas. Clinically evident acromegaly from a growth hormone (GH)-producing adenoma is evident in approximately 10% of adults. Psammomatous melanotic schwannoma (PMS), a rare tumor of the nerve sheath, occurs in an estimated 10% of affected individuals. The median age of diagnosis is 20 years.
Dowling-Degos disease is a skin condition characterized by a lacy or net-like (reticulate) pattern of abnormally dark skin coloring (hyperpigmentation), particularly in the body's folds and creases. These skin changes typically first appear in the armpits and groin area and can later spread to other skin folds such as the crook of the elbow, back of the knee, and under the breasts. Less commonly, pigmentation changes can also occur on the neck, wrists, back of the hands, face, scalp, scrotum, and vulva. These areas of hyperpigmentation typically cause no health problems.Individuals with Dowling-Degos disease may also have dark spots (lesions) on the face and back that resemble blackheads, red bumps around the mouth that resemble acne, or pitted scars on the face similar to acne scars but with no history of acne. Fluid-filled sacs within the hair follicle (pilar cysts) may develop, most commonly on the scalp. Rarely, affected individuals have patches of skin that are unusually light in color (hypopigmented).In rare cases, individuals with Dowling-Degos disease experience itching (pruritus) or burning sensations on the skin. These feelings can be triggered by UV light, sweating, or friction on the skin.The pigmentation changes characteristic of Dowling-Degos disease typically begin in late childhood or in adolescence, although in some individuals, features of the condition do not appear until adulthood. New areas of hyperpigmentation tend to develop over time, and the other skin lesions tend to increase in number as well. While the skin changes associated with Dowling-Degos disease may cause distress or anxiety, they typically cause no other health problems.A condition called Galli-Galli disease has signs and symptoms similar to those of Dowling-Degos disease. In addition to pigmentation changes, individuals with Galli-Galli disease also have a breakdown of cells in the outer layer of skin (acantholysis). Acantholysis can cause skin irritation and itchiness and lead to reddened or missing patches of skin (erosions). These conditions used to be considered two separate disorders, but Galli-Galli disease and Dowling-Degos disease are now regarded as the same condition.
Increased focal pigmentation of the vermilion of the lips.
A benign skin tumor characterized as a small, dome-shaped dermal nodule composed of fibroblasts in a dense collagenous background with storiform organization. Rarely, multiple lesions can occur in connection with Cowden's disease.
An acquired form of collagenoma that appears in childhood. It is characterized by discrete, firm, skin-colored, and slightly elevated cutaneous papules, nodules or plaques that may be generalized, or found on the trunk and the extremities.
The material exuded from a wound, either surgical or traumatic.
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
A bent (flexed) knee joint that cannot be straightened actively or passively.
Intrapelvic bulging of the medial acetabular wall.
A group of conditions used to describe polyarthritis occurring in children.
A group of chronic, inflammatory childhood diseases characterized by arthritis and enthesitis. This disorder can affect the axial skeleton in late childhood or young adulthood.
Chronic infantile neurologic cutaneous and articular (CINCA) syndrome is a severe chronic inflammatory disease of early onset, characterized by cutaneous symptoms, central nervous system involvement, and arthropathy (Feldmann et al., 2002). See also familial cold autoinflammatory syndrome-1 (FCAS1, CAPS1; 120100), an allelic disorder with a less severe phenotype.
Rapidly destructive shoulder joint and bone disease found mainly in elderly, and predominantly in women. It is characterized by SHOULDER PAIN; JOINT INSTABILITY; and the presence of crystalline CALCIUM PHOSPHATES in the SYNOVIAL FLUID. It is associated with ROTATOR CUFF INJURIES.
Noninflammatory degenerative disease of the knee joint consisting of three large categories: conditions that block normal synchronous movement, conditions that produce abnormal pathways of motion, and conditions that cause stress concentration resulting in changes to articular cartilage. (Crenshaw, Campbell's Operative Orthopaedics, 8th ed, p2019)
An autoimmune, connective tissue chronic inflammatory disorder affecting the skin, joints, kidneys, lungs, heart, and the peripheral blood cells. It is more commonly seen in women than men. Variants include discoid and systemic lupus erythematosus.
A manifestation of systemic lupus erythematosus with a widespread vesiculobullous eruption.
A self-limited skin rash that appears in the neonatal period and usually resolves in four to six months after birth. It is caused by placental transfer of maternal autoantibodies, usually anti-Ro antibody. In a minority of cases, it is associated with congenital heart block, hepatitis, or thrombocytopenia. The mothers of the affected babies may be asymptomatic or suffer from systemic lupus erythematosus, Sjogren's syndrome, or rheumatoid arthritis.
An autoimmune disorder which does not meet classification criteria used to establish the presence of other well-defined connective tissue diseases.
An autoimmune, connective tissue disorder in which the patient exhibits features from two or more diseases. These typically include systemic sclerosis, dermatomyositis, polymyositis, rheumatoid arthritis, systemic lupus erythematosus, and Sjogren syndrome; in pediatrics the respective pediatric entities are encountered.
A self-limiting, rapidly growing, non-encapsulated benign neoplasm that arises from the soft tissues. It is characterized by the presence of plump spindle-shaped fibroblasts, multinucleated osteoclast-like giant cells, chronic inflammatory infiltrate, red blood cell extravasation, and high mitotic activity.
Fukuyama congenital muscular dystrophy (FCMD) is characterized by hypotonia, symmetric generalized muscle weakness, and CNS migration disturbances that result in changes consistent with cobblestone (previously type II) lissencephaly with cerebral and cerebellar cortical dysplasia. Mild, typical, and severe phenotypes are recognized. Onset typically occurs in early infancy, with a poor suck, weak cry, and floppiness. Affected individuals have contractures of the hips, knees, and interphalangeal joints. Later features include myopathic facial appearance, pseudohypertrophy of the calves and forearms, motor and speech retardation, intellectual disability, seizures, ophthalmologic abnormalities including visual impairment and retinal dysplasia, and progressive cardiac involvement in individuals older than age ten years. Swallowing disturbance occurs in individuals with severe FCMD and in individuals older than age ten years, leading to recurrent aspiration pneumonia and death.
Ullrich congenital muscular dystrophy is characterized by generalized muscle weakness and striking hypermobility of distal joints in conjunction with variable contractures of more proximal joints and normal intelligence. Additional findings may include kyphoscoliosis, protruded calcanei, and follicular hyperkeratosis. Some patients manifest at birth and never achieve independent ambulation, whereas others maintain ambulation into adulthood. Progressive scoliosis and deterioration of respiratory function is a typical feature (summary by Kirschner, 2013). Genetic Heterogeneity of Ullrich Congenital Muscular Dystrophy UCMD2 (616470) is caused by mutation in the COL12A1 gene (120320) on chromosome 6q.
Desmin-related myopathies (DRM) are a clinically and genetically heterogeneous group of muscular disorders defined morphologically by intrasarcoplasmic aggregates of desmin (DES; 125660), usually accompanied by other protein aggregates. Approximately one-third of DRM are caused by mutations in the desmin gene (Ferreiro et al., 2004). For other forms of DRM, see primary desminopathy (601419).
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of joint contractures that begin in early childhood, slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles, and cardiac involvement that may manifest as palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure. Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both inter- and intrafamilial variability. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade.
X-linked myotubular myopathy (X-MTM), also known as myotubular myopathy (MTM), is characterized by muscle weakness that ranges from severe to mild. Approximately 80% of affected males present with severe (classic) X-MTM characterized by polyhydramnios, decreased fetal movement, and neonatal weakness, hypotonia, and respiratory failure. Motor milestones are significantly delayed and most individuals fail to achieve independent ambulation. Weakness is profound and often involves facial and extraocular muscles. Respiratory failure is nearly uniform, with most individuals requiring 24-hour ventilatory assistance. It is estimated that at least 25% of boys with severe X-MTM die in the first year of life, and those who survive rarely live into adulthood. Males with mild or moderate X-MTM (~20%) achieve motor milestones more quickly than males with the severe form; many ambulate independently, and may live into adulthood. Most require gastrostomy tubes and/or ventilator support. In all subtypes of X-MTM, the muscle disease is not obviously progressive. Female carriers of X-MTM are generally asymptomatic, although manifesting heterozygotes are increasingly being identified. In affected females, symptoms range from severe, generalized weakness presenting in childhood, with infantile onset similar to affected male patients, to mild (often asymmetric) weakness manifesting in adulthood. Affected adult females may experience progressive respiratory decline and ultimately require ventilatory support.
Centronuclear myopathy is a condition characterized by muscle weakness (myopathy) and wasting (atrophy) in the skeletal muscles, which are the muscles used for movement. The severity of centronuclear myopathy varies among affected individuals, even among members of the same family.People with centronuclear myopathy begin experiencing muscle weakness at any time from birth to early adulthood. The muscle weakness slowly worsens over time and can lead to delayed development of motor skills, such as crawling or walking; muscle pain during exercise; and difficulty walking. Some affected individuals may need wheelchair assistance as the muscles atrophy and weakness becomes more severe. In rare instances, the muscle weakness improves over time.Some people with centronuclear myopathy experience mild to severe breathing problems related to the weakness of muscles needed for breathing. People with centronuclear myopathy may have droopy eyelids (ptosis) and weakness in other facial muscles, including the muscles that control eye movement. People with this condition may also have foot abnormalities, a high arch in the roof of the mouth (high-arched palate), and abnormal side-to-side curvature of the spine (scoliosis). Rarely, individuals with centronuclear myopathy have a weakened heart muscle (cardiomyopathy), disturbances in nerve function (neuropathy), or intellectual disability.A key feature of centronuclear myopathy is the displacement of the nucleus in muscle cells, which can be viewed under a microscope. Normally the nucleus is found at the edges of the rod-shaped muscle cells, but in people with centronuclear myopathy the nucleus is located in the center of these cells. How the change in location of the nucleus affects muscle cell function is unknown.
Myotonic dystrophy that is present at birth.
An autoinflammatory disease characterized by sterile bone lesions which are multifocal and/or recurrent.
Necrotic changes in the bone tissue of the femoral head due to interruption of blood supply.
Hypochondroplasia is a skeletal dysplasia characterized by short stature; stocky build; disproportionately short arms and legs; broad, short hands and feet; mild joint laxity; and macrocephaly. Radiologic features include shortening of long bones with mild metaphyseal flare; narrowing of the inferior lumbar interpedicular distances; short, broad femoral neck; and squared, shortened ilia. The skeletal features are very similar to those seen in achondroplasia but tend to be milder. Medical complications common to achondroplasia (e.g., spinal stenosis, tibial bowing, obstructive apnea) occur less frequently in hypochondroplasia but intellectual disability and epilepsy may be more prevalent. Children usually present as toddlers or school-age children with decreased growth velocity leading to short stature and limb disproportion. Other features also become more prominent over time.
A form of skeletal dysplasia characterized by shortening of the bones of the middle segments of the limbs (i.e., the radii, ulnae, tibiae and fibulae).
Pseudoachondroplasia is characterized by normal length at birth and normal facies. Often the presenting feature is a waddling gait, recognized at the onset of walking. Typically, the growth rate falls below the standard growth curve by approximately age two years, leading to a moderately severe form of disproportionate short-limb short stature. Joint pain during childhood, particularly in the large joints of the lower extremities, is common. Degenerative joint disease is progressive; approximately 50% of individuals with pseudoachondroplasia eventually require hip replacement surgery.
An autosomal dominant or recessive form of craniotubular hyperostosis due to mutation(s) in the SOST gene, encoding sclerostin. This condition is characterized by massive generalized hyperostosis and sclerosis, especially involving the skull and facial bones, which is so severe that the resulting facial distortion is referred to as 'leontiasis ossea'; the bone deposition results in progressive stenosis of craniofacial foramina and can lead to severe neurologic impairment in childhood.
Any degenerative disorder affecting one or more vertebral discs of the cervical spine.
The presence of abnormal calcium deposition of the intervertebral disk.
A Schmorl's node is the herniation of nucleus pulposus through the cartilaginous and bony end plate into the body of the adjacent vertebra.
An abnormal lack of stability of the cervical spine.
Abnormally increased movement at the junction between the first cervical (atlas) and the second cervical (axis) vertebrae as a result of either a bony or ligamentous anomaly.
An inherited genetic disorder that affects the connective tissues. Representative examples include Ehlers-Danlos syndrome and Marfan syndrome.
Death of a live newborn during the first 28 days of life.
A fetal heart rate above 160 bpm that is sustained for longer than 10 minutes.
A fetal heart rate below 110 bpm that is sustained for longer than 10 minutes.
An abnormally increased width of the cranial sutures for age-related norms (generally resulting from delayed closure).
An abnormally high hydrogen ion concentration (umbilical arterial blood pH less than 7.00) in fetal blood or tissue.
A rare form of anaphylaxis for which triggers cannot be identified despite a detailed history and careful diagnostic assessment. [PMID:28890861]
Acquired form of angioedema due to deficiency of C1 inhibitor
The calendar date on which a person was born.
Definition: Relates a place (playing Entity) as the location where a living subject (scoping Entity) died.
A measurement of the total number of pregnancy events experienced by the female subject prior to the current pregnancy.
A measurement of the total number of fetuses, which includes alive and dead fetuses, present in the uterus.
Symptoms, physical examination results, and/or laboratory test results related to the nervous system.
Tonic seizures with a sustained, forced conjugate ocular, cephalic and/or truncal rotation or lateral deviation from the midline.
A condition in which a person experiences a given stimulus, usually tactile but more rarely other sensory modalities, on the corresponding opposite side of the body from the side of the stimulation.
Perception of two images secondary to misalignment of the eyes.
Saccadic undershoot, i.e., a saccadic eye movement that has less than the magnitude that would be required to gain fixation of the object.
A saccade that overshoots the target with the dynamic saccade.
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
The palpebral fissure inclination is more than two standard deviations below the mean.
Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures.
Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.
Drooping of the upper eyebrow below the superior orbital rim. []
Loss of elasticity of the upper and lower eyelids causing the skin to sag and bulge.
An ophthalmologic sign in young children resulting from upward-gaze paresis. In this condition, the eyes appear driven downward, the sclera may be seen between the upper eyelid and the iris, and part of the lower pupil may be covered by the lower eyelid. [HPO:probinson, pmid:17030938]
Inflammation and infection of the lacrimal canaliculus area in the LACRIMAL APPARATUS.
Keratinization of the bulbar conjunctiva near the limbus (corneoscleral junction), resulting in a raised spot.
Diffusely large eye (with megalocornea) without glaucoma.
An eye that is more deeply recessed into the plane of the face than is typical. [pmid:19125427]
Reduced transparency of the stroma of cornea. [DDD:gblack]
Reduced transparency of the central posterior portion of the corneal stroma.
Reduced depth of the anterior chamber, i.e., the anteroposterior distance between the cornea and the iris is decreased.
Increased depth of the anterior chamber, i.e., the anteroposterior distance between the cornea and the iris is increased.
An abnormal appearance of the beam of light traveling through the anterior chamber of the eye in a slit lamp examination. The flare is produced by an increased concentration of proteins in the aqueous humor in the anterior chamber. [PMID:16196117]
Tiny deposits corresponding to cells floating in the anterior chamber of the eye. This appearance is typically associated with intraocular inflammation leading to breakdown of the blood-aqueous barrier and resulting in an increase in the number of cells and in the aqueous humor. Grading (SUN Working Group) is performed by estimating the number of cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp. [ORCID:0000-0003-0986-4123, PMID:16196117]
A finding indicating the quick and brisk constriction of the pupils in response to light.
Asymmetry between the two irides or asymmetry between different parts of one iris.
Tremulousness of the iris on movement of the eye, occurring in subluxation of the lens.
Presence of iris pigment epithelium on the anterior surface of the iris.
Separation of the vitreous humor from the retina.
The presence of an increased number of twists and turns of the retinal artery.
Presence of multiple yellowish-white lesions of various size and configuration on the retina not related to vascular lesions.
Lack of the foveal reflex, which normally occurs as a result of the reflection of light from the ophthalmoscope in the foveal pit upon examination. The foveal reflex is a bright pinpoint of light that is observed to move sideways or up and down in response to movement of the opthalmoscope.
A type of retinal exudate located in the subretinal space between the sensory retina and the retinal pigment epithelium.
The ratio of the diameter of the optic cup compared to the diameter of the optic disc.
Symptoms, physical examination results, and/or laboratory test results related to the ear.
Sensation of itching or other similar sensations in the ear.
A question about whether an individual has or had numbness.
Feeling of grittiness or having something in the eye; frequently caused by a foreign body. Other possible causes include corneal abrasion, corneal ulcer, inturned eye lash or acute conjunctivitis.
Episodic childhood musculoskeletal pain, usually brief (a few minutes), intense, nocturnal, involving both legs, with no identifiable cause or sequelae.
Painful sensation in any part of the urinary tract.
Recurrent episodes of pain localized to the anus or lower rectum which lasts seconds to minutes. There is no pain between episodes.
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
An abnormal communication between the skin and another organ or cavity.
Violaceous papules overlying the dorsal and lateral aspects of the metacarpophalangeal and proximal interphalangeal joints.
A skin condition consisting of both macules and papules.
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
When viewed on end (with the digit tip pointing toward the examiner's eye) the curve of the nail forms a tighter curve of convexity.
Longitudinal, linear prominences in the nail plate.
Nail that appears thin when viewed on end.
A feeling of doubt concerning two or more possible alternatives or courses of action.
A risk factor for suicide attempts and completions, it is the most common of all suicidal behavior, but only a minority of ideators engage in overt self-harm.
The level of happiness or contentment that an individual professes, or is observed to display with regards to their life situation.
Emotion characterized by feelings of tension, worried thoughts, and inadequacy in a social setting.
Excessive or pathological tendency to save and collect possessions.
Increased motor activity that is not goal directed.
A lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment.
Aggressive behavior by a more powerful party that results in physical harm to or emotional distress of the victim.
To annoy, taunt, or joke with in a manner that is considered either petty, harassing, or playful.
Negelcting one's own needs and well-being.
Self-inflicted harm without the intent to die.
Behavioral characteristics of a girl which are considered typical of the gender role of a male.
Behavioral characteristics of a boy which are considered typical of the gender role of a female.
A lack of facial expression often with staring eyes and a slightly open mouth.
Cracking, fissuring, and peeling of the skin of the lips.
A finding that refers to a person with erythematous face.
An abnormal morphology (form) of the face or its components.
A level of awareness that can be described as varied and intermittent periods of consciousness and unconsciousness.
A reduction in the ability to perform or withstand activities that induce physical or mental exertion.
Abnormally heavy or prolonged loss of blood.
Mental functions that produce the natural sleep leading to optimal physical and mental rest and relaxation.
Outcomes that describe an individual's emotional health and related selfperception
A state of increased vulnerability to stressors, following declines in function and reserves across multiple physiologic systems, characterized by MUSCLE WEAKNESS; FATIGUE; slowed motor performance; low physical activity; and unintentional weight loss.
Failure to meet, or late achievement of developmental milestones.
Deposits of ADIPOSE TISSUE throughout the body. The pattern of fat deposits in the body regions is an indicator of health status. Excess ABDOMINAL FAT increases health risks more than excess fat around the hips or thighs, therefore, WAIST-HIP RATIO is often used to determine health risks.
Skin lumpiness or skin surface dimpling often seen on the thighs, buttocks and abdomen. It is due to protrusion of SUBCUTANEOUS FAT into the DERMIS layer of skin.
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).
A single transverse palmar crease is found in 5% of newborns and is frequently inherited as a familial trait. However, single palmar creases can be associated with Down's syndrome and other genetic disorders, or with fetal alcohol syndrome.
Severe chills accompanied by vigorous shaking.
Communication by means of words or sounds uttered through the mouth.
Susceptible to a failure of thermoregulation that may result in a core body temperature below the normal diurnal range, which may compromise health.
The historical fact that a legal or consanguineous family member has died.
An indication that an individual is living in their home.
The earning of income directly from customers, clients, or other organizations rather than as a specified salary or wages from an employer.
Resumption of normal work routine following a hiatus or period of absence due to injury, disability, or other reasons.
An indication that an individual is living in a nursing home.
Ability to move purposefully in own environment independently with or without assistive device
A person who was not smoking at the time of the interview and has smoked less than 100 cigarettes in their life.
Individuals who do not necessarily identify with any particular race or others who do not wish to self select into a racial category(ies).
Having been legally made a member of a family.
Symptoms, physical examination results, and/or laboratory test results related to the respiratory system.
A pulling inward of the soft tissues between the ribs upon inhalation. This is a sign of increased use of the chest muscles for breathing and is a manifestation of respiratory distress.
A change from the normal breathing pattern in an infant, child, or adult, in terms of the amplitude and frequency of inhalations and exhalations.
Symptoms, physical examination results, and/or laboratory test results related to the cardiovascular system.
A galloping sound on cardiac auscultation because of an abnormally audible fourth heart sound.
Isolated breast development prior to the normal age of pubertal onset in females.
Swelling and dimpling of the surface of the skin, which is typically associated with carcinoma of the breast.
Congenital failure to develop, and absence of, the nipple.
An indication that an individual's uterus is not present.
The first day of the female's last menstrual cycle.
The length of time of the menses cycle, measured from the beginning of one menstrual period to the beginning of the next.
An approximate calculated date at which the conception event took place.
Any intrauterine symptom or result related to the fetus.
An observation of the fetal heart that may or may not be abnormal.
A cardinal movement in labor when the head of the fetus folds towards its chest to assume the smallest anero-posterior diameter for the presenting part during delivery.
A position of the fetus during the labor and delivery process where the fetal back is straight, the head position is deflexed and upright on the spine.
A position of the fetus during the labor and delivery process where the head is extended back.
A kind of breech presentation in which one or both hips are extended and one or both of the fetus' feet are pointing down and entering the birth canal.
A fetal presentation during delivery in which the shoulder descends into the birth canal first.
A presentation of the fetal hand or arm before the fetal vertex.
A position adopted by the fetus during labor when its head moves down into the maternal pelvic cavity.
Amniotic fluid containing the earliest stools of a mammalian infant.
Clinical and laboratory findings about the placenta.
The total length of the umbilical cord as measured from all segments. A cord length less than 30 or 35 cm is considered ""short"" whereas one greater than 70 cm is ""long"".
Extent to which maternal well-being is within normal limits from delivery of placenta to completion of involution
A sudden and involuntary contraction of the bladder wall.
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
Decreased width of the bony bridge of the nose.
A splitting of the nasal tip. Visually assessable vertical indentation, cleft, or depression of the nasal tip.
Positioning of the nasal tip inferior to the nasal base.
Slender, slit-like aperture of the nostril. [HPO:probinson]
A fissure in the gingiva (gums), i.e., the mucosal tissue that lies over the mandible and maxilla.
Decreased length and width of the tongue.
The presence of an abnormally short lingual frenulum.
A clinical term that indicates the presence of a white mucosal patch in the interarytenoid area. In most cases histologic examination reveals keratosis.
A question about whether an individual has or had difficulty swallowing liquids.
Bleeding originating from the anal area.
Symptoms, physical examination results, and/or laboratory rest results related to the muscles and bones.
Reduced inferior to superior extent of the thorax.
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Increased width (cross-sectional diameter) of the clavicles.
An excessive upward convexity of the lateral clavicle.
The two portions of the clavicle (corresponding to the two primary ossification centers of the clavicle) are connected by a fibrous bridge that is contiguous with the periosteum, and a synovial membrane develops, resulting in a clavicle with a bipartite appearance radiographically. Congenital pseudarthrosis of the clavicle generally presents as a painless mass or swelling over the clavicle.
The two portions of the clavicle (corresponding to the two primary ossification centers of the clavicle) are connected by a fibrous bridge that is contiguous with the periosteum, and a synovial membrane develops, resulting in a clavicle with a bipartite appearance radiographically. Congenital pseudarthrosis of the clavicle generally presents as a painless mass or swelling over the clavicle. [HPO:probinson, pmid:22295044]
A developmental anomaly with absence of one or more ribs.
A row of beadlike prominences at the junction of a rib and its cartilage, resembling a rosary.
Radiolucent focal defect of a rib shaft.
A small hollow area or sinus present at birth and located just above the crease of the buttocks. In most cases, pilonidal dimples are benign and may just be accompanied by increased hair growth in the area.
A bending or abnormal curvature affecting a long bone of the arm.
A hand in which the fingers are of nearly equal length and deflected at the first interphalangeal joint, so as to give a forklike shape consisting of separation of the first and second as well as the third and fourth digits.
The gradual reduction in girth of the digit from proximal to distal. [pmid:19125433]
Increased thumb width without increased dorso-ventral dimension.
Tibial torsion is inward twisting (medial rotation) (PATO:0002155) of the tibia.
Shortening of the legs related to developmental hypoplasia of the bones of the leg.
A developmental defect resulting in the presence of fewer than the normal number of toes.
A type of spastic cerebral palsy characterized by increased muscle tone of all four extremities.
A sensation of tightness in the ankle joint when attempting to move it, especially after a period of inactivity.
A reduction in the strength of the facial muscles.
The shoulder, or pectoral, girdle is composed of the clavicles and the scapulae. Shoulder-girdle weakness refers to lack of strength of the muscles attaching to these bones, that is, lack of strength of the muscles around the shoulders.
Weakness of the muscles of the pelvic girdle (also known as the hip girdle), that is, lack of strength of the muscles around the pelvis.
Reduced strength of the musculature of the distal extremities. [HPO:probinson]
Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face. [HPO:probinson]
Sensation of losing one's grip and falling.
An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again.
Truncal ataxia is a sign of ataxia characterized by instability of the trunk. It usually occurs during sitting.
A reduction from the normal range of the average amount of hemoglobin per red blood cell (27 to 31 picograms/cell). A reduced mean corpuscular hemoglobin (MCH) may indicate a hypochromic anemia, but the MCH may be normal if both the total hemoglobin and the red blood cell count are reduced.
A peripheral blood finding in which a large number of erythrocytes are shaped in a slightly oval-shaped form.
A laboratory test result indicating the presence of blast cells in a blood sample.
Abnormally low level of monocytes in the blood.
A blood group indicating the presence on erythrocytes of only the A form of the H Antigen.
A blood group indicating the presence on erythrocytes of both the A and B forms of the H Antigen.
A blood group indicating the absence on erythrocytes of both the A and B forms of the H Antigen.
response of germs to antibiotics treatment
Catalysis of the reaction: a beta-lactam + H2O = a substituted beta-amino acid. [EC:3.5.2.6]
An abnormally reduced amount of creatinine in the blood.
An elevated lipid concentration in the blood.
The blood pressure in the pulmonary artery during the contraction of the left ventricle of the heart.
The blood pressure in the pulmonary artery during ventricular relaxation (diastole).
The recorded time interval between the initiation of inhalation and the point at which no further lung volume expansion occurs.
The recorded time interval between the initiation of exhalation and the time at which no further lung volume reduction occurs.
The measure of an individual's cardiac output as divided by their body surface area (CI= CO/BSA). This calculation is a useful function to determine an individual's cardiac performance in relation to their body size, providing an overview of global cardiovascular function.
Deposition of calcium salts in the aortic valve.
An abnormal widening of the diameter of the pulmonary artery.
Pattern of blood flow in the heart that deviates from the normal circuit of the circulatory system from the left side of the heart to the right.
Pattern of blood flow in the heart that deviates from the normal circuit of the circulatory system from the right side of the heart to the left.
Pattern of blood flow in the heart that deviates from the normal circuit of the circulatory system from both right side of the heart to the left and vice versa.
The pressure within the CARDIAC ATRIUM. It can be measured directly by using a pressure catheter (see HEART CATHETERIZATION). It can be also estimated using various imaging techniques or other pressure readings such as PULMONARY CAPILLARY WEDGE PRESSURE (an estimate of left atrial pressure) and CENTRAL VENOUS PRESSURE (an estimate of right atrial pressure).
A blood pressure that refers to the average over a cardiac cycle
A derangement in the normal functioning of the sinoatrial node. Typically, SA node dysfunction is manifest as sinoatrial exit block or sinus arrest, but may present as an absolute or relative bradycardia in the presence of a stressor. It may be associated with bradycardia-tachycardia syndrome
A type of arrhythmia that originates above the ventricles, whereby the electrical impulse propagates down the normal His Purkinje system similar to normal sinus rhythm.
A slower than normal heart rate (in adults, slower than 60 beats per minute).
An electrocardiographic finding of an ectopic impulse originating in the AV junction presenting as a QRS complex of supraventricular origin which is not preceded by a P wave. (CDISC)
An electrocardiographic finding of premature atrial complexes which are not conducted to the ventricle, and which are not followed by a QRS complex. (CDISC)
An electrocardiographic finding of two sinus beats followed by a premature atrial complex for 3 or more consecutive cycles; a regularly irregular rhythm of normal and abnormal P waves in a 2-1 ratio. (CDISC)
An electrocardiographic finding in which two premature ventricular complexes occur sequentially. (CDISC)
A QRS complex that is less than 120 milliseconds on electrocardiogram, reflexing rapid activation of the ventricles via the normal His-Purkinje system. It may indicate the presence of an arrhythmia originating above or within the His bundle.
An electrocardiographic finding of a prolonged ST segment, resulting in an increased QT interval, without lengthening of the T wave duration; this may be observed in hypocalcemia. (CDISC)
The time interval between the start of the P wave and the beginning of the QRS complex in the cardiac cycle.
An electrocardiographic finding that represents depolarization of the ventricular myocardium. Normally the ventricles are activated simultaneously.
These are spontaneous firing action potentials stimulated by needle movement of an injured muscle fiber. There is propagation to, but not past, the needle tip. This inhibits the display of the negative deflection of the waveform.
A menstrual cycle in which no ovulation occurs.
The number of fetal cardiac beats per minute, considered as the reference value against which measurements in the future can be made.
Fluctuations in the baseline fetal heart rate, determined in a 10 minute window while excluding accelerations and decelerations. They are irregular in amplitude and frequency and are visually quantitated as the amplitude of the peak to trough in beats per minute. Sinusoidal patterns are also excluded.
A decrease in the fetal heart rate that has a duration of less than 10 minutes.
A gradual decrease in the fetal heart rate and return to baseline that is associated with a uterine contraction. The nadir of the deceleration occurs at the same time as the peak of the uterine contraction, and the time from onset to nadir of the deceleration is greater than or equal to 30 seconds.
A gradual decrease in the fetal heart rate and return to baseline that is associated with a uterine contraction. The nadir of the deceleration occurs after the peak of the uterine contraction, and the time from onset to nadir of the deceleration is greater than or equal to 30 seconds.
An abrupt increase is defined as an increase from the onset of acceleration to the peak in less than 30 seconds. To be called an acceleration, the peak must be greater than or equal to 15 bpm, and the acceleration must last greater than or equal to 15 seconds from the onset to return to baseline.
Observation of patency of angle of anterior chamber.
Observation of appearance of angle of anterior chamber.
state of body in regard to ingestion and excretion of nitrogen; difference between nitrogen intake and total nitrogen excretion.
A measurement of the airway conductance relative to lung volume.
Pulmonary compliance measured during the movement of air, such as during active inspiration.
Pulmonary compliance measured without air flow, such as during an inspiratory pause.
The maximum volume of air an individual can exhale from the point of maximal inhalation.
The fastest flow rate of gas noted during the inspiratory cycle.
A diagnostic indicator of vascular resistance that is calculated by dividing the difference between the peak systolic and minimum diastolic blood velocities by the mean velocity.
Adequacy of the blood flow through body organs to function at the cellular level
A measurement of the total number of birth events at which the fetus is of at least 20 weeks gestation, or of a birth weight of at least 350 grams if the gestational age is unknown, which is born without signs of life at the time of delivery, and with an Apgar score of zero at both one and five minutes.
A measurement of the total number of instances in which there has been a termination of pregnancy happening before the fetus is able to sustain independent life.
A measurement of the total number of induced abortions experienced by a female subject.
A measurement of the total number of spontaneous abortions (in which the fetus is less than 20 weeks gestational age) experienced by a female subject.
A response indicating that an individual requires no help with their personal grooming care.
A response indicating that an individual is fecally continent.
A response indicating that an individual is dependent on others for dressing.
A response indicating that an individual can dress independently of help from others.
A response indicating that an individual is independent with use of a wheelchair.
A response indicating that an individual can go up and down stairs independently of help from others.
A response indicating that an individual is dependent on others to bathe.
A melanoma arising from an atypical intraepithelial melanocytic hyperplasia.
A diffuse anaplastic glioma characterized by the presence of both an astrocytic and an oligodendroglial component and the absence of information on the IDH genes status.
A malignant neoplasm arising from the choroid plexus. It shows anaplastic features and usually invades neighboring brain structures. Cerebrospinal fluid metastases are frequent. (Adapted from WHO)
An aggressive malignant mesenchymal neoplasm of the nervous system or soft tissues. It is characterized by the presence of a sarcomatous component (most often rhabdomyosarcoma) and a ganglionic or a neuroectodermal component.
A WHO grade III neuroepithelial neoplasm composed of neoplastic, mature ganglion cells and anaplastic glial cells. The anaplastic changes in the glial component and high MIB-1 and TP53 labeling indices may indicate aggressive behavior. However, the correlation of histological anaplasia with clinical outcome is inconsistent. (Adapted from WHO)
A meningioma that affects the choroid plexus.
A WHO grade I meningioma characterized by the presence of prominent chronic inflammatory infiltrates that predominate over the meningioma cells.
A WHO grade II morphologic variant of meningioma characterized by the presence of clear glycogen-rich polygonal cells.
A WHO grade II meningioma characterized by the presence of brain invasion and an increased mitotic activity, or at least three of the following morphologic features: small cells, high cellularity, prominent nucleoli, lack of architectural pattern, and necrosis.
A morphologic variant of schwannoma characterized by hypercellularity, Antoni A pattern, and the absence of well-formed Verocay bodies.
A benign peripheral nerve sheath tumor characterized by the presence of Schwann cells, axons, and perineurial fibroblasts. It usually arises from the skin of the head and neck or the oral mucosa. It presents as a solitary and painless nodular mass.
A craniopharyngioma composed of sheets of squamous epithelium which separate to form pseudopapillae. This variant typically lacks nuclear palisading, wet keratin, calcification, and cholesterol deposits. Clinically, endocrine deficiencies are more often associated with papillary craniopharyngioma than with the adamantinomatous type. (Adapted from WHO)
A craniopharyngioma consisting of broad strands, cords and bridges of a multistratified squamous epithelium with peripheral palisading of nuclei. Diagnostic features include nodules of compact 'wet' keratin and dystrophic calcification. (Adapted from WHO)
An encephalocele located between bregma and lambda.
Herniation of spinal cord tissue and meninges through a defect in the lumbar region of the vertebral column. The protrusion of the tissue is flush with the level of the skin surface.
Herniation of spinal cord tissue and meninges through a defect in the thoracic region of the vertebral column. The protrusion of the tissue is flush with the level of the skin surface.
Herniation of spinal cord tissue and meninges through a defect in the cervical region of the vertebral column. The protrusion of the tissue is flush with the level of the skin surface.
A form of closed neural tube defect in which the spinal tissue lies within the spinal cord having a junction between the spinal cord and the lipoma. Intact skin covers the defect. Neurologic findings first appear during the second year of life.
A very rare congenital brain defect in which the cerebral cortex, striatum, globus pallidus, thalamus, hypothalamus, and eyes are absent or rudimentary.
Abnormal increase of cerebrospinal fluid in the subdural space of the brain.
A type of holoprosencephaly in which most of the right and left cerebral hemispheres and lateral ventricles are separated but the most rostral aspect of the telencephalon, the frontal lobes, are fused, especially ventrally.
A type of holoprosencephaly characterized by the presence of a single ventricle and no separation of the cerebral hemisphere. The single midline ventricle is often greatly enlarged.
A partial failure of the development of the corpus callosum. [HPO:curators]
Dysplasia and dysgenesis of the corpus callosum are nonspecific descriptions that imply defective development of the corpus callosum. The term dysplasia is applied when the morphology of the corpus callosum is altered as a congenital trait. For instance, the corpus callosum may be hump-shaped, kinked, or a striped corpus callosum that lacks an anatomically distinct genu and splenium.
The presence of atrophy (wasting) of the corpus callosum.
A form of lissencephaly characterized by an uneven cortical surface with a so called 'cobblestone' appearace. There are no distinguishable cortical layers.
Malformation of the cerebral cortex due to improper migration of neurons in utero.
Colpocephaly is an anatomic finding in the brain manifested by occipital horns that are disproportionately enlarged in comparison with other parts of the lateral ventricles.
Enlargement of all or parts of one cerebral hemisphere.
Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen.
Gillespie syndrome is usually diagnosed in the first year of life by the presence of fixed dilated pupils in a hypotonic infant. Affected individuals have a characteristic form of iris hypoplasia in which the pupillary border of the iris exhibits a scalloped or 'festooned' edge, with iris strands extending onto the anterior lens surface at regular intervals. The key extraocular features of Gillespie syndrome are congenital hypotonia, progressive cerebellar hypoplasia, and ataxia, as well as variable cognitive impairment that is usually mild (summary by Gerber et al., 2016 and McEntagart et al., 2016).
22q11.2 deletion syndrome (which is also known by several other names, listed below) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2.22q11.2 deletion syndrome has many possible signs and symptoms that can affect almost any part of the body. The features of this syndrome vary widely, even among affected members of the same family. Common signs and symptoms include heart abnormalities that are often present from birth, an opening in the roof of the mouth (a cleft palate), and distinctive facial features. People with 22q11.2 deletion syndrome often experience recurrent infections caused by problems with the immune system, and some develop autoimmune disorders such as rheumatoid arthritis and Graves disease in which the immune system attacks the body's own tissues and organs. Affected individuals may also have breathing problems, kidney abnormalities, low levels of calcium in the blood (which can result in seizures), a decrease in blood platelets (thrombocytopenia), significant feeding difficulties, gastrointestinal problems, and hearing loss. Skeletal differences are possible, including mild short stature and, less frequently, abnormalities of the spinal bones.Many children with 22q11.2 deletion syndrome have developmental delays, including delayed growth and speech development, and learning disabilities. Later in life, they are at an increased risk of developing mental illnesses such as schizophrenia, depression, anxiety, and bipolar disorder. Additionally, affected children are more likely than children without 22q11.2 deletion syndrome to have attention deficit hyperactivity disorder (ADHD) and developmental conditions such as autism spectrum disorder that affect communication and social interaction.Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with the autosomal dominant form of Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.
Gross dilatation of the vein of Galen, being fed by large anomalous vessel or vessels arising from the carotid or basilar circulation.
Meeting of the medial eyebrows in the midline.
This may present as a partial or complete duplication of the eyebrows.
The orbits do not lie on the same horizontal plane, that is, one eye is lower than the other.
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
An abnormality of the pinna, which is also referred to as the auricle or external ear.
The presence of both a left and a right ductus arteriosus.
Multiple indentations and/or elevations on the edge and/or surface of the tongue producing an irregular surface contour.
A benign (noncancerous) tumorlike malformation made up of an abnormal mixture of cells and tissues that originates in the tongue.
A congenital disorder characterized by blockage or absence of the intrahepatic bile ducts.
Ectopic liver is a rare developmental anomaly in which liver tissue is situated outside the liver. Thus, ectopic liver refers to autonomous islands of normal liver parenchyma located outside the liver. The term ectopic liver is also used, to include liver appendices attached to the native liver by a thin stalk although being fully separated from the latter.
A failure to develop of the lower part of the vagina.
Absence of both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the testis.
Absence of a testis from the scrotum on one side owing to failure of the testis or testes to descend through the inguinal canal to the testis.
Ventral skinfold extending from penis to scrotum.
The 17q12 recurrent deletion syndrome is characterized by variable combinations of the three following findings: structural or functional abnormalities of the kidney and urinary tract, maturity-onset diabetes of the young type 5 (MODY5), and neurodevelopmental or neuropsychiatric disorders (e.g., global developmental delay, intellectual disability, autism spectrum disorder, schizophrenia, anxiety, and bipolar disorder). Using a method of data analysis that avoids ascertainment bias, the authors determined that multicystic kidneys and other structural renal anomalies occur in 80% to 85% of affected individuals, MODY5 in approximately 40%, and some degree of developmental delay or learning disability in approximately 50%. MODY5 is most often diagnosed before age 25 years (range: age 10-50 years).
Congenital renal hypoplasia characterized by small kidneys; reduced nephron number; tubular and glomerular hypertrophy.
A unilateral form of developmental dysplasia of the kidney.
A bilateral form of developmental dysplasia of the kidney.
The presence of many cysts in the kidney.
A condition in which the urachus fails to close proximal to the bladder, resulting in a non-detrusor, blind-ending pouch at the dome of the bladder.
A narrowing of the opening of the urethra at the external meatus.
An abnormal osseous union (fusion) between the ulna and the humerus.
Unilateral atrophy (reduction in size) of an arm.
Synostosis (bony fusion) involving one or more bones of the carpus (scaphoid, lunate, triquetrum, trapezium, trapezoid, capitate, hamate, pisiform).
With the hand relaxed and the thumb in the plane of the palm, the axis of the thumb forms an angle of at least 90 degrees with the long axis of the hand.
A congenital abnormality characterized by hypoplasia or absence of the thumb. It may be associated with other congenital abnormalities.
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Unilateral atrophy (reduction in size) of a leg.
Congenital structural abnormalities of the LOWER EXTREMITY.
Proximal femoral focal deficiency is a deformity manifested by hypoplasia of a variable portion of the femur with shortening of the entire limb.
A condition in which middle parts of the foot (toes and metatarsals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic 3rd toe over absent 2nd or 3rd toes as far as oligo- or monodactyl feet.
Syndactyly with fusion of toes two and three.
Syndactyly with fusion of fingers two and three.
A reduction in the magnitude or amount of ossification of the skull.
Cleft of the soft palate (also known as the velum, or muscular palate) as a result of a developmental defect occurring between the 7th and 12th week of pregnancy. Cleft soft palate can cause functional abnormalities of the Eustachian tube with resulting middle ear anomalies and hearing difficulties, as well as speech problems associated with hypernasal speech due to velopharyngeal insufficiency.
Hard-palate submucous clefts are characterized by bony defects in the midline of the bony palate that are covered by the mucous membrane of the roof of the mouth. It may be possible to detect a submucous cleft hard palate upon palpation as a notch in the bony palate.
Individuals with trigonocephaly have a keel-shaped forehead with wide biparietal diameter, resulting in a triangular shape of the head. Trigonocephaly results from premature closure of the metopic sutures and usually occurs sporadically (summary by Frydman et al., 1984). Genetic Heterogeneity of Isolated Trigonocephaly Also see trigonocephaly-2 (TRIGNO2; 614485), caused by mutation in the FREM1 gene (608944) on chromosome 9p22.
A kind of craniosynostosis affecting the sagittal suture.
Cloverleaf skull, or Kleeblattschaedel, consists of a trilobular skull with craniosynostosis. The condition shows pathogenetic variability and etiologic heterogeneity. The cause of isolated cloverleaf skull is unknown (Cohen, 2009). Cohen (1975) pointed out that Kleeblattschaedel is a component of many syndromes, e.g., it is found in some cases of Crouzon syndrome (123500), Pfeiffer syndrome (101600), and Carpenter syndrome (201000). Cohen (2009) listed 12 monogenic disorders with cloverleaf skull as a feature, including type II thanatophoric dysplasia (187601), which accounts for 40% of all cloverleaf skull syndromes. Cohen (2009) published photographs of cloverleaf skull in various syndromes.
Absence of one half of the vertebral body in the lumbar spine.
Absence of one half of the vertebral body in the thoracic spine.
Absence of one half of the vertebral body in the cervical spine.
Agenesis of one or more vertebrae of the cervical vertebral column.
A defect in the pars interarticularis of the vertebral arch of a lumbar or sacral vertebra that is present at the time of birth.
An abnormality related to a defect of vertebral separation during development.
Congenital lack of development of the muscles, which are then replaced by a mixture of dense fat and fibrous tissue.
Schneckenbecken dysplasia is a perinatally lethal skeletal dysplasia. The German term 'Schneckenbecken' refers to the distinctive, snail-like appearance of the ilia that results from a medial bone projection from the inner iliac margin. Other hallmarks of the disorder include thoracic hypoplasia, severe flattening of the vertebral bodies, and short, thick long bones (summary by Hiraoka et al., 2007).
Pseudodiastrophic dysplasia is characterized by short-limbed short stature at birth, facial dysmorphism (hypertelorism, flat nose, prominent cheeks, micrognathia), cleft palate, and a distinctive skeletal phenotype including narrow thorax, scoliosis, rhizomelia, ulnar deviation of the wrist, proximal interphalangeal joint dislocation, dislocation of large joints, particularly of the elbows, and talipes equinovarus (summary by Yap et al., 2016).
The dyssegmental dysplasias are lethal forms of neonatal short-limbed dwarfism. Handmaker et al. (1977) coined the term 'dyssegmental dysplasia' because of the marked differences in size and shape of the vertebral bodies (anisospondyly), which he attributed to errors in segmentation. Fasanelli et al. (1985) proposed that there are different forms of dyssegmental dwarfism, a lethal Silverman-Handmaker type (224410) and a less severe Rolland-Desbuquois type. The Rolland-Desbuquois form is lethal in about 40% of patients. Although many patients survive beyond the newborn period, all exhibit neonatal distress (summary by Hennekam et al., 2010).
Syndrome with characteristics of disproportionate short-trunked short stature, pectus carinatum, short arms, short and broad hands, short metatarsals, flat and broad feet, coxa vara, genu valgum, osteoarthritis, arthrosis and moderate-to-serious gait impairment. The syndrome has been described among Venezuelan Indians of the Yukpa (Irapa) tribe and three siblings from a Mexican mestizo family. Autosomal recessive inheritance has been suggested, but the causative gene has not yet been identified.
Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement in the absence of inflammation. Onset – typically between ages three and six years – begins with the involvement of the interphalangeal joints. Over time, involvement of large joints and the spine causes significant joint contractures, gait disturbance, and scoliosis and/or kyphosis, resulting in abnormal posture and significant morbidity. Despite the considerable arthropathy, pain is not a major presenting feature of this condition. Initially height is normal; however, short stature (<3rd centile) becomes evident in adolescence as the skeletal changes progress.
Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis, and growth retardation develop at a later age. Other frequent multisystem manifestations include hepatic and renal dysfunction, mental retardation, and cardiovascular abnormalities (summary by Delepine et al., 2000).
Opsismodysplasia is a rare skeletal dysplasia involving delayed bone maturation. Clinical signs observed at birth include short limbs, small hands and feet, relative macrocephaly with a large anterior fontanel, and characteristic craniofacial abnormalities including a prominent brow, depressed nasal bridge, a small anteverted nose, and a relatively long philtrum. Death in utero or secondary to respiratory failure during the first few years of life has been reported, but there can be long-term survival. Typical radiographic findings include shortened long bones with delayed epiphyseal ossification, severe platyspondyly, metaphyseal cupping, and characteristic abnormalities of the metacarpals and phalanges (summary by Below et al., 2013 and Fradet and Fitzgerald, 2017).
The corner fracture type of spondylometaphyseal dysplasia is characterized by flake-like, triangular, or curvilinear ossification centers at the edges of irregular metaphyses that simulate fractures. These 'corner fractures,' which involve the distal tibia, the ulnar aspect of the distal radius, the proximal humerus, and the proximal femur, represent irregular ossification at the growth plates and secondary ossification centers. They become larger in older children and disappear after growth has stopped. In addition, severe scoliosis has been observed in FN1-associated SMDCF, whereas developmental coxa vara is less often seen, and odontoid abnormalities have not been reported (Lee et al., 2017).
Spondyloenchondrodysplasia is a rare skeletal dysplasia involving vertebral dysplasia and enchondroma-like lesions in the pelvis and long bones. The vertebral bodies show dorsally accentuated platyspondyly with disturbance of ossification. Clinical abnormalities such as short stature, rhizomelic micromelia, increased lumbar lordosis, barrel chest, facial anomalies, and clumsy movements may be present (Menger et al., 1989). Also see spondyloenchondrodysplasia with immune dysregulation (SPENCDI; 607944), which is caused by mutation in the ACP5 gene (171640). It has been suggested by some that the various clinical manifestations observed in association with SPENCD may be pleiotropic manifestations of a single nosologic entity defined by the presence of typical spondylar and metaphyseal changes (see Renella et al., 2006).
Langer mesomelic dysplasia (LMD) is characterized by severe limb aplasia or severe hypoplasia of the ulna and fibula, and a thickened and curved radius and tibia. These changes can result in displacement deformities of the hands and feet. Hypoplasia of the mandible is also observed (Langer, 1967). See also Leri-Weill dyschondrosteosis (127300), a less severe phenotype that results from heterozygous defect in the SHOX or SHOXY genes.
Cranioectodermal dysplasia (CED), a ciliopathy also known as Sensenbrenner syndrome, is a multisystem disorder with skeletal involvement (narrow thorax, shortened proximal limbs, and brachydactyly), ectodermal features (widely-spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth retardation, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus/epicanthus, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage renal disease (ESRD) in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy, other manifestations of ciliopathies, are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur.
A rare osteochondrodysplasia characterized by short stature, joint laxity, multiple dislocations, vertebral and metaphyseal abnormalities, and advanced carpotarsal ossification. Two forms have been identified: type 1 caused by mutation in the gene CANT1 and type 2 caused by mutations in the gene XYLT1.
Spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1) is characterized by vertebral abnormalities and ligamentous laxity that result in spinal misalignment and progressive severe kyphoscoliosis, thoracic asymmetry, and respiratory compromise resulting in early death. Nonaxial skeletal involvement includes elbow deformities with radial head dislocation, dislocated hips, clubfeet, and tapered fingers with spatulate distal phalanges. Many affected children have an oval face, flat midface, prominent eyes with blue sclerae, and a long philtrum. Palatal abnormalities and congenital heart disease are also observed (summary by Smith et al., 1999). Patients with a similar phenotype and fractures have been described (Malfait et al., 2013). Genetic Heterogeneity of Spondyloepimetaphyseal Dysplasia with Joint Laxity Also see SEMDJL2 (603546), caused by mutation in the KIF22 gene (603213) on chromosome 16p11, and SEMDJL3 (618395), caused by mutation in the EXOC6B gene (607880) on chromosome 2p13.
Microcephalic osteodysplastic primordial dwarfism type II is characterized by intrauterine growth retardation, severe proportionate short stature, and microcephaly. It is distinct from Seckel syndrome (see 210600) by more severe growth retardation, radiologic abnormalities, and absent or mild mental retardation (summary by Willems et al., 2010).
Osteoporosis-pseudoglioma syndrome is a rare condition characterized by severe thinning of the bones (osteoporosis) and eye abnormalities that lead to vision loss. In people with this condition, osteoporosis is usually recognized in early childhood. It is caused by a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple bone fractures, including in the bones that form the spine (vertebrae). Multiple fractures can cause collapse of the affected vertebrae (compressed vertebrae), abnormal side-to-side curvature of the spine (scoliosis), short stature, and limb deformities. Decreased bone mineral density can also cause softening or thinning of the skull (craniotabes).Most affected individuals have impaired vision at birth or by early infancy and are blind by young adulthood. Vision problems are usually caused by one of several eye conditions, grouped together as pseudoglioma, that affect the light-sensitive tissue at the back of the eye (the retina), although other eye conditions have been identified in affected individuals. Pseudogliomas are so named because, on examination, the conditions resemble an eye tumor known as a retinal glioma.Rarely, people with osteoporosis-pseudoglioma syndrome have additional signs or symptoms such as mild intellectual disability, weak muscle tone (hypotonia), abnormally flexible joints, or seizures.
Dysosteosclerosis is a rare bone dysplasia associated with neurodevelopmental deterioration. There is sclerosis and platyspondyly with progressive metaphyseal expansion and alteration of bone density. The early craniotubular bone modeling and clinical presentation resemble osteopetrosis (summary by Elcioglu et al., 2002).
A syndrome of trichothiodystrophy (sulfur-deficient brittle hair) with photosensitivity, ichthyosiform erythroderma, progeria-like facies, growth and mental retardation, occasional infertility, and variable other defects. When photosensitivity is present, the syndrome is known as PIBIDS or PIBI(D)S; without photosensitivity it is referred to as IBIDS. Syndromes which have brittle hair, impaired intelligence, decreased fertility, and short stature, but no ichthyosis, are referred to as BIDS (see Amish brittle hair syndrome).
Osteopathia striata with cranial sclerosis is an X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae (Jenkins et al., 2009). In males, the disorder is usually associated with fetal or neonatal lethality. Occasional surviving males have, in addition to hyperostosis, cardiac, intestinal, and genitourinary malformations. Osteosclerosis in the cranial and facial bones leads to disfigurement and to disability due to pressure on cranial nerves, e.g., deafness. Osteopathia striata is a frequent feature of focal dermal hypoplasia (FDH; 305600). Although early reports of familial cases of this disorder appeared to suggest autosomal dominant inheritance (see, e.g., Horan and Beighton, 1978 and Konig et al., 1996), reappraisal of the literature (Behninger and Rott, 2000; Rott et al., 2003) and the finding of a molecular basis for the disorder by Jenkins et al. (2009) confirms that the inheritance pattern is X-linked dominant. Affected males who survive have a more severe phenotype than affected females, and sporadic male cases may result from somatic mosaicism (Behninger and Rott, 2000).
Lenz-Majewski hyperostotic dwarfism is a rare condition characterized by intellectual disability, sclerosing bone dysplasia, distinct craniofacial and dental anomalies, loose skin, and distal limb anomalies, particularly brachydactyly and symphalangism. Patients have multiple radiographic abnormalities due to progressive generalized hyperostosis that affects the cranium, vertebrae, and diaphyses of tubular bones, leading to severe growth retardation (summary by Sousa et al., 2014).
SOST-related sclerosing bone dysplasias include sclerosteosis and van Buchem disease, both disorders of progressive bone overgrowth due to increased bone formation. The major clinical features of sclerosteosis are progressive skeletal overgrowth, most pronounced in the skull and mandible, and variable syndactyly, usually of the second (index) and third (middle) fingers. Affected individuals appear normal at birth except for syndactyly. Facial distortion due to bossing of the forehead and mandibular overgrowth is seen in nearly all individuals and becomes apparent in early childhood with progression into adulthood. Hyperostosis of the skull results in narrowing of the foramina, causing entrapment of the seventh cranial nerve (leading to facial palsy) with other, less common nerve entrapment syndromes including visual loss (2nd cranial nerve), neuralgia or anosmia (5th cranial nerve), and sensory hearing loss (8th cranial nerve). In sclerosteosis, hyperostosis of the calvarium reduces intracranial volume, increasing the risk for potentially lethal elevation of intracranial pressure. Survival of individuals with sclerosteosis into old age is unusual, but not unprecedented. The manifestations of van Buchem disease are generally milder than sclerosteosis and syndactyly is absent; life span appears to be normal.
Osteoglophonic dysplasia is a condition characterized by abnormal bone growth that leads to severe head and face (craniofacial) abnormalities, dwarfism, and other features. The term osteoglophonic refers to the bones (osteo-) having distinctive hollowed out (-glophonic) areas that appear as holes on x-ray images.Premature fusion of certain bones in the skull (craniosynostosis) typically occurs in osteoglophonic dysplasia. The craniosynostosis associated with this disorder may give the head a tall appearance, often referred to in the medical literature as a tower-shaped skull, or a relatively mild version of a deformity called a cloverleaf skull. Characteristic facial features in people with osteoglophonic dysplasia include a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), flattening of the bridge of the nose and of the middle of the face (midface hypoplasia), a large tongue (macroglossia), a protruding jaw (prognathism), and a short neck. People with this condition usually have no visible teeth because the teeth never emerge from the jaw (clinical anodontia). In addition, the gums are often overgrown (hypertrophic gingiva).Infants with osteoglophonic dysplasia often experience failure to thrive, which means they do not gain weight and grow at the expected rate. Affected individuals have short, bowed legs and arms and are short in stature. They also have flat feet and short, broad hands and fingers.The life expectancy of people with osteoglophonic dysplasia depends on the extent of their craniofacial abnormalities; those that obstruct the air passages and affect the mouth and teeth can lead to respiratory problems and cause difficulty with eating and drinking. Despite the skull abnormalities, intelligence is generally not affected in this disorder.
Infantile myofibromatosis is a rare mesenchymal disorder characterized by the onset of nodules in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about 50% of patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life (summary by Arcangeli and Calista, 2006). Genetic Heterogeneity of Infantile Myofibromatosis See also IMF2 (615293), caused by mutation in the NOTCH3 gene (600276).
Dermochondrocorneal dystrophy, or Francois syndrome, is a rare disorder characterized by the development of skin nodules, acquired deformities of the extremities, and a corneal dystrophy. The corneal dystrophy is central and superficial with whitish subepithelial opacities (summary by Bierly et al., 1992).
Winchester syndrome presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning, similar to multicentric osteolysis, nodulosis, and arthropathy (MONA; 259600), but subcutaneous nodules are characteristically absent. Various additional features including coarse face, corneal opacities, gum hypertrophy, and EKG changes have been reported (summary by Zankl et al., 2007).
Mandibuloacral dysplasia with type A lipodystrophy (MADA) is an autosomal recessive disorder characterized by growth retardation, craniofacial anomalies with mandibular hypoplasia, skeletal abnormalities with progressive osteolysis of the distal phalanges and clavicles, and pigmentary skin changes. The lipodystrophy is characterized by a marked acral loss of fatty tissue with normal or increased fatty tissue in the neck and trunk. Some patients may show progeroid features. Metabolic complications can arise due to insulin resistance and diabetes (Young et al., 1971; Simha and Garg, 2002; summary by Garavelli et al., 2009). See also MAD type B (MADB; 608612), which is caused by mutation in the ZMPSTE24 gene (606480).
Familial expansile osteolysis is an autosomal dominant bone dysplasia characterized by increased bone remodeling with osteolytic lesions mainly affecting the appendicular skeleton. There is medullary and cortical expansion of the bone without sclerosis, leading to painful and disabling deformities and tendency to pathologic fracture. Clinical features include onset of conductive hearing loss in childhood, premature loss of teeth, and variably increased serum alkaline phosphatase (summary by Palenzuela et al., 2002 and Elahi et al., 2007).
A rare autosomal dominant inherited form of ichthyosis. It is characterized by the presence of an erythematous skin with blisters at birth. The skin subsequently becomes dry, flaky and hyperkeratotic.
Anton-Lamprecht (1978) stated that 4 genetic disorders of keratinization are known to have a structural defect of tonofibrils. (1) In the harlequin fetus (242500), an abnormal x-ray diffraction pattern of the horn material points to a cross-beta-protein structure instead of the normal alpha-protein structure of keratin. (2) Bullous ichthyosiform erythroderma (EHK; 113800) is characterized by an early formation of clumps and perinuclear shells due to an abnormal arrangement of tonofibrils. (3) In the Curth-Macklin form of ichthyosis hystrix (146590), concentric unbroken shells of abnormal tonofilaments form around the nucleus. (4) In ichthyosis hystrix gravior, only rudimentary tonofilaments are found with compensatory production of mucous granules. Goldsmith (1976) used the designation of epidermolytic hyperkeratosis for the condition that is called bullous congenital ichthyosiform erythroderma (BCIE) when generalized and ichthyosis hystrix when localized.
Epidermolysis bullosa simplex is one of a group of genetic conditions called epidermolysis bullosa that cause the skin to be very fragile and to blister easily. Blisters and areas of skin loss (erosions) occur in response to minor injury or friction, such as rubbing or scratching. Epidermolysis bullosa simplex is one of the major forms of epidermolysis bullosa. The signs and symptoms of this condition vary widely among affected individuals. Blistering primarily affects the hands and feet in mild cases, and the blisters usually heal without leaving scars. Severe cases of this condition involve widespread blistering that can lead to infections, dehydration, and other medical problems. Severe cases may be life-threatening in infancy.Researchers have identified four major types of epidermolysis bullosa simplex. Although the types differ in severity, their features overlap significantly, and they are caused by mutations in the same genes. Most researchers now consider the major forms of this condition to be part of a single disorder with a range of signs and symptoms.The mildest form of epidermolysis bullosa simplex, known as the localized type (formerly called the Weber-Cockayne type), is characterized by skin blistering that begins anytime between childhood and adulthood and is usually limited to the hands and feet. Later in life, skin on the palms of the hands and soles of the feet may thicken and harden (hyperkeratosis).The Dowling-Meara type is the most severe form of epidermolysis bullosa simplex. Extensive, severe blistering can occur anywhere on the body, including the inside of the mouth, and blisters may appear in clusters. Blistering is present from birth and tends to improve with age. Affected individuals also experience abnormal nail growth and hyperkeratosis of the palms and soles.Another form of epidermolysis bullosa simplex, known as the other generalized type (formerly called the Koebner type), is associated with widespread blisters that appear at birth or in early infancy. The blistering tends to be less severe than in the Dowling-Meara type.Epidermolysis bullosa simplex with mottled pigmentation is characterized by patches of darker skin on the trunk, arms, and legs that fade in adulthood. This form of the disorder also involves skin blistering from early infancy, hyperkeratosis of the palms and soles, and abnormal nail growth.In addition to the four major types described above, researchers have identified another skin condition related to epidermolysis bullosa simplex, which they call the Ogna type. It is caused by mutations in a gene that is not associated with the other types of epidermolysis bullosa simplex. It is unclear whether the Ogna type is a subtype of epidermolysis bullosa simplex or represents a separate form of epidermolysis bullosa.Several other variants of epidermolysis bullosa simplex have been proposed, but they appear to be very rare.
An abnormality of dermatoglyphs (fingerprints), which are present on fingers, palms, toes, and soles.
A rare neurofibroma with an infiltrative growth pattern. It involves the skin and subcutaneous tissue and grows in a plaque-like fashion. Malignant transformation is rare.
A plaque representing a connective-tissue nevus. Connective tissue naevi are uncommon skin lesions that occur when the deeper layers of the skin do not develop correctly or the components of these layers occur in the wrong proportion. Shagreen patches are oval-shaped and nevoid, skin-colored or occasionally pigmented, smooth or crinkled, The word shagreen refers to a type of roughened untanned leather.
A teratogenic disorder observed in a newborn or child of a mother who was exposed to retinoids during pregnancy. Manifestations include growth delay, skull, facial, heart, and central nervous system malformations.
Fetal embryopathy associated with maternal thalidomide use during pregnancy characterized by phocomelia of one or all limbs, other limb defects such as thumb abnormalities, and other structural anomalies that may include facial hemangioma, esophageal and duodenal atresia, tetralogy of Fallot, renal agenesis, and anomalies of the external ear. Long term complications may include Moebius syndrome or autism.
A teratogenic disorder observed in a newborn or child of a mother who was exposed to methotrexate during pregnancy. Manifestations of the syndrome include craniofacial, digital, and skeletal malformations.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 12 in somatic cells.
The presence of a third copy of chromosome 11 in somatic cells.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 10 in somatic cells.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 9 in somatic cells.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 8 in somatic cells.
A rare genetic syndrome characterized by the deletion of the short arm of chromosome 18. It is associated with mental and growth retardation, prominent ears and ptosis.
A condition in which some or all of the cells of the body contain extra genetic material from chromosome 18. Clinical features of this condition may include the following: spina bifida, hearing loss, cleft lip, cleft palate, undescended testes, rocker bottom feet, micrognathia, low set ears, cardiac anomalies (ventricular septal defect, atrial septal defect, patent ductus arteriosus, tetralogy of Fallot), intellectual disability, holoprosencephaly, pituitary dysplasia, seizures, autoimmune disorders, hip dysplasia, and/or congenital cataracts.
A person who has a chromosome composition of 46 XY and who is phenotypically female.
A person who has a chromosome composition of 46 XX and who is phenotypically male.
Post-transplant lymphoproliferative disorder (PTLD) is a polyclonal (benign) or clonal (malignant) proliferation of lymphoid cells that develops as a consequence of immunosuppression in a recipient of a solid organ or bone marrow allograft. PTLDs comprise a spectrum ranging from early, Epstein-Barr virus (EBV)-driven polyclonal lymphoid proliferations to EBV-positive or EBV- negative lymphomas of predominantly B-cell or less often T-cell type. (WHO, 2001)
A rapidly growing, poorly circumscribed, mass-forming proliferation that arises from the subcutaneous tissues. It is characterized by the presence of spindle-shaped fibroblasts, round ganglion-like cells, myxoid to collagenous stroma formation, and high mitotic activity. It recurs only rarely following local excision and does not metastasize.
A rare self-limiting, rapidly growing, non-encapsulated benign neoplasm that arises from the vessels. It is characterized by the presence of plump spindle-shaped fibroblasts, multinucleated osteoclast-like giant cells, chronic inflammatory infiltrate, red blood cell extravasation, and high mitotic activity.
A non-Hodgkin lymphoma or rarely Hodgkin lymphoma that arises from the spleen.
An aggravating factor is defined as an external factor that leads to the a sign or symptom that is already present getting worse or becoming more severe.
An x-ray of the renal arteries that reveals normal results.
Granulomatous inflammation of the testis. It is characterized by the formation of granulomas around the seminiferous tubules. History of trauma may be present. It is assumed to be a reactive process due to autoimmune phenomena.
Palpation exam confirms presence of a breast lump.
No lump was palpated during breast examination.
A laboratory test result indicating a finding outside the parameters of normal urine measurements.
Graphic representation and categorization of the electrical vectors produced by the depolarization and repolarization of myocardial tissue.
Results that are standard and expected for the reference population with any of the parameters used to measure the mechanical function of the lungs and associated structures.
A laboratory test result indicating the results of the lab test are within normal parameters for the age and population.
A deviation from normal range of the erythrocyte sedimentation rate (ESR), a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen. A decreased ESR may be seen in polycythemia or in certain blood diseases in which red blood cells have an irregular or smaller shape that causes slower settling.
Living alone. Maps to PD1-2 Living arrangement (IS) 00742 [A].
Protected against infectious disease by either specific or non-specific mechanisms.
The psychological or physiological need to take a substance in oder to experience its effects or to avoid the effects of its absence.
The flower-heads of either the plant Anthemis nobilis or the plant Matricaria chamomilla. Chamomile has a warm aromatic odour and a very bitter taste and contains volatile oils which are a mixture of butyl and amyl angelates and valerates. Due to its coumarin constituents, large doses may interfere with coagulation. (NCI04)
A complex mixture consisting of allergenic proteins derived from natural sources used for allergy diagnosis by skin or provocation testing.
A regional lymph node TNM finding indicating that there is no evidence of regional lymph node metastasis.
A general term that refers to a TNM finding of cancer metastases in several regional lymph nodes. The definition of N2 TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases in 4-9 axillary lymph nodes; for cutaneous melanoma it refers to metastases in 2-3 regional lymph nodes; for colorectal cancer it refers to metastases in 4 or more regional lymph nodes; and for bladder cancer it refers to metastases in multiple regional lymph nodes in the true pelvis.
A general term that refers to a TNM finding of cancer metastases in multiple lymph nodes. The definition of N3 TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases in 10 or more axillary lymph nodes; for cutaneous melanoma it refers to metastases in 4 or more regional lymph nodes; for gastric cancer it refers to metastases in 7 or more regional lymph nodes; and for bladder cancer it refers to metastases in common iliac lymph nodes.
A general term that refers to a TNM finding of cancer metastases usually in a limited number of regional lymph nodes. The definition of N1 TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to micrometastases or metastases in 1-3 axillary lymph nodes; for cutaneous melanoma it refers to metastasis in 1 regional lymph node; for colorectal cancer it refers to metastases in 1-3 regional lymph nodes; and for bladder cancer it refers to metastasis in 1 regional lymph node in the true pelvis.
A clinical and/or pathologic distant metastasis TNM finding indicating the spread of cancer to distant anatomic sites.
The measurement of the specified component / analyte, organism or clinical sign above the limit of detection of the performed test or procedure.
The presence of the specified component / analyte, organism or clinical sign could not be determined within the limit of detection of the performed test or procedure.
Description:There was (or is to be) no change to the item. This is primarily used when this element has not changed, but other attributes in the instance have changed.
Description:Patient exhibits no reaction to the challenge agent.
The patient is considered as carrier based on the testing results. A carrier is an individual who carries an altered form of a gene which can lead to having a child or offspring in future generations with a genetic disorder. Deprecation Comment:This antimicrobial susceptibility test interpretation concept is recommended by OO to be deprecated as it is no longer recommended for use in susceptibility testing by CLSI (reference CLSI document M100-S22; Vol. 32 No.3; CLSI Performance Standards for Antimicrobial Susceptibility Testing; Twenty-Second Informational Supplement. Jan 2012).
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Flesh-colored papule in or around the nail bed. Ungual fibromas may be periungual (arising under the proximal nail fold ) or subungual (originating under the nail plate).
infection by a microorganism following an infection by another kind of microorganism.
A clinical course finding indicating that a disease presents with systemic manifestations.
Platelets collected from a single donor and suspended in a specified volume of original plasma.
A specific humoral or cell-mediated immune response against autologous (self) antigens. An autoimmune process may produce or be caused by autoimmune disease and may be developmentally complex, not necessarily pathological, and possibly pervasive.
An aliphatic carboxylic acid, also known as enanthic acid, used in the synthesis of esters for products such as fragrances and artificial flavor preparations.
DNA sequence rearrangements that result in the creation of multiple immunoglobulins or T-cell receptors being expressed in a lymphocyte population.
A distant metastasis TNM finding indicating that there is no evidence of distant metastasis.
A TNM finding indicating the spread of cancer to distant anatomic sites. The definition of M1a TNM finding depends on the specific type of cancer that it refers to; for example, for colorectal cancer it refers to metastasis confined to one organ or site (e.g., liver, lung, ovary, nonregional node); for prostate cancer it refers to metastasis to non-regional lymph node(s); for bone cancer it refers to metastasis to the lung.
A TNM finding indicating the spread of cancer to distant anatomic sites. The definition of M1c TNM finding depends on the specific type of cancer that it refers to; for example, for prostate cancer it refers to metastasis to anatomic site(s) other than bone, with or without bone disease; for retinoblastoma it refers to central nervous system metastasis; for melanoma of the uvea it refers to distant metastasis, with the largest diameter of the largest metastasis measuring 8.0 cm or more.
A distant metastasis TNM finding indicating that the status of distant metastasis cannot be assessed.
A TNM finding indicating the spread of cancer to distant anatomic sites. The definition of M1b TNM finding depends on the specific type of cancer that it refers to; for example, for colorectal cancer it refers to metastases in more than one organ/site or the peritoneum; for prostate cancer it refers to metastasis to bone(s); for bone cancer it refers to metastasis to distant sites other than lung.
A general term that refers to a TNM finding of cancer metastases in several regional lymph nodes. The definition of N2a TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases in 4 to 9 axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm); for cutaneous melanoma it refers to micrometastases in 2-3 regional lymph nodes; for colorectal cancer it refers to metastases in 4-6 regional lymph nodes.
A general term that refers to a TNM finding of cancer metastases in several regional lymph nodes. The definition of N2b TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases only in clinically detected ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary lymph node metastases; for cutaneous melanoma it refers to macrometastases in 2-3 regional lymph nodes; for colorectal cancer it refers to metastases in seven or more regional lymph nodes.
A general term that refers to a TNM finding of cancer metastases in several regional lymph nodes. The definition of N2c TNM finding depends on the specific type of cancer that it refers to; for example, for cutaneous melanoma it refers to intralymphatic metastases (in transit or satellite metastases) without metastatic nodes; for lip and oral cavity cancer it refers to metastases in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension.
A regional lymph node TNM finding indicating that the status of regional lymph nodes cannot be assessed.
In children, urine protein greater than or equal to 40mg/m^2/h; alternatively, greater than or equal to 0.25gm/mmol creatinine or 2gm/gm creatinine obtained from a first morning specimen.
Increase in thickness of the basal lamina of the glomerulus of the kidney.
Not connected or associated e.g. by kinship.
A morphologic finding indicating the cutaneous melanoma depth of invasion into the dermis and subcutaneous tissue.
Definition: A factor, such as a microorganism, chemical substance, or form of radiation, whose presence, excessive presence, or (in deficiency diseases) relative absence is essential, in whole or in part, for the occurrence of a condition. Constraint: The use of this participation is limited to observations.
Where something is available or from where it originates.
The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.
Formation of stones in any part of the URINARY TRACT, usually in the KIDNEY; URINARY BLADDER; or the URETER.
Damage to the kidney and renal tubules resulting from heavy metal exposure.
A syndrome characterized by the presence of structural malformations that are present at birth and can be attributed to an exogenous cause.
Awareness of external senses of the limb after physical loss.
A bilateral type of conductive hearing impairment.
A bilateral form of sensorineural hearing impairment.
A severe form of hypospadias in which the urethral opening is located at the junction of the penis and scrotum.
Hypospadias with location of the urethral meatus in the perineal region.
Abnormally high blood pressure in a newborn child.
Dietary patterns which have been found to be important in reducing disease risk.
A nutritional plan based on the presumed diet of pre-agricultural human ancestors. It consists mainly of MEAT, EGGS, NUTS, roots and fresh VEGETABLES and FRUITS, and excludes GRAIN, LEGUMES, DAIRY PRODUCTS, and refined DIETARY SUGARS.
A type of dysarthria related to bilateral damage of the upper motor neuron tracts of the pyramidal and extra- pyramidal tracts. Speech of affected individuals is slow, effortful, and has a harsh vocal quality.
A delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts. [HPO:probinson]
A delay in the acquisition of the ability to understand the speech of others.
A degree of language development that is significantly below the norm for a child of a specified age.
Thinking about ending or making plans to end another's life.
A sensation of discomfort or distress that is distinct and intensely focused.
Actions performed to obtain information about past illness and health status
An event in the personal medical history of heart failure, a condition in which the heart is unable to pump enough blood to meet the body's requirements.
Feeling of excessive energy, which may be associated with increased activity.
Apparently small scrotum for age. [pmid:23650202]
The left ventricular volume calculated as the difference between the epicardium delimited volume and the left ventricular chamber volume.
An abnormal increase in the size of nasopharyngeal adenoids. []
Death of live newborn between 7and 27 days after birth.
Hydrops fetalis is a descriptive term for generalized edema of the fetus, with fluid accumulation in extravascular components and body cavities. It is not a diagnosis in itself, but a symptom and end-stage result of a wide variety of disorders. In the case of immune hydrops fetalis, a frequent cause is maternofetal incompatibility as in that related to a number of genetic anemias and metabolic disorders expressed in the fetus; in other instances, it remains idiopathic and likely multifactorial (summary by Bellini et al., 2009). Nonimmune hydrops fetalis accounts for 76 to 87% of all described cases of hydrops fetalis (Bellini et al., 2009). Genetic Heterogeneity of Hydrops Fetalis In southeast Asia, alpha-thalassemia is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (141800) and HBA2 (141850) genes. A few cases have been reported that had 1 apparently normal alpha-globin gene, termed the hemoglobin H (613978) hydrops fetalis syndrome (summary by Chui and Waye, 1998). Other genetic disorders predisposing to NIHF include other congenital anemias, such as erythropoietic porphyria (e.g., 606938.0013), and many metabolic disorders, such as one form of Gaucher disease (e.g., 606463.0009), infantile sialic acid storage disease (269920), mucopolysaccharidosis type VII (253220), glycogen storage disease IV (232500), and congenital disorder of glycosylation type Ia (212065).
Fluid accumulation in multiple fetal anatomic cavities attributable to a maternal immune response against fetal blood cell antigens.
Transient cyanotic discoloration of the hands and feet, especially fingers and toes, in a newborn.
An infant whose weight at birth is less than 1000 grams (2.2 lbs), regardless of GESTATIONAL AGE.
A deficiency or slowing down of growth pre- and postnatally. [HPO:probinson]
A fetus exceeding 90% of expected weight for gestational age.
An infectious disorder of newborn infants that is characterized by a systemic inflammatory response most commonly caused by bacteria.
Rickets that usually affects premature infants. Factors that contribute to the development of neonatal rickets include calcium, phosphorus, or calciferol deficiency. It manifests with spontaneous fractures, respiratory distress, and growth developmental delays.
In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms.
The maximum pressure exerted into the systemic arterial circulation during the contraction of the right ventricle of the heart.
The pressure in the left ventricle at any point prior to the ejection of its contents into the aorta (systole).
The pressure within the left ventricle following the completion of diastolic filling, just prior to systole.
The resistance to blood flow offered by the pulmonary vasculature, which is normally one sixth of SVR. The major determinant of PVR is pulmonary vessel constriction, most often caused by hypoxia and/or hypercardia. Prolonged elevated PVR can cause right heart failure.
Judgment and explanation of the significance, meaning, application, or limitation of an assessment instrument and an obtained score or scores.
Any natural or synthetic composition that replicates the structure or function of a native component of blood.
A benign form of endometrial hyperplasia with increased number of endometrial glands and thickened endometrium. Simple hyperplasia has little risk of progression to endometrial carcinoma.
A hamartomatous polyp that occurs in the stomach, small and large intestines, and rarely within the esophagus, nasopharynx and the urinary tract. The Peutz-Jeghers polyps are grossly lobulated and dark. Microscopically, they have a central core of smooth muscle covered by mucosa. The smooth muscle shows tree-like branching. The question of whether or not the Peutz-Jeghers polyp is precancerous is a matter of controversy. The loss of heterozygosity on chromosome 19p (where the responsible gene LKB1 is located) suggests that the increased risk of malignancy may be due to malignant transformation from hamartoma to adenocarcinoma. --2002
A common condition characterized by transient partial or total paralysis of skeletal muscles and areflexia that occurs upon awakening from sleep or less often while falling asleep. Stimuli such as touch or sound may terminate the episode, which usually has a duration of seconds to minutes. This condition may occur in normal subjects or be associated with NARCOLEPSY; CATAPLEXY; and hypnagogic HALLUCINATIONS. The pathophysiology of this condition is closely related to the normal hypotonia that occur during REM sleep. (From Adv Neurol 1995;67:245-271)
Abnormally increased volume of the first heart sound. []
A reduction in goal-directed behavior, that is, motivation, the determinant of behavior and adaptation that allows individuals to get started, be energized to perform a sustained and directed action.
A term that refers to high grade B-cell lymphoma, not otherwise specified or high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements.
An uncommon mature T-cell lymphoma of intraepithelial lymphocytes. It usually arises from the small intestine, most commonly the jejunum or ileum. Other less frequent primary anatomic sites include the duodenum, stomach, colon, or outside the gastrointestinal tract. It is seen with increased frequency in regions with a high prevalence of celiac disease.
Primary bilateral pulmonary hypoplasia is defined as quantitative and/or qualitative underdevelopment of bronchial and pulmonary tissue unrelated to an underlying disorder (Langer and Kaufmann, 1986).
A reduction of the pressure inside the cranium (skull) and thereby in the brain tissue and cerebrospinal fluid.
A general term that refers to a TNM finding of cancer metastases usually in a limited number of regional lymph nodes. The definition of N1a TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastasis in 1 to 3 axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm); for cutaneous melanoma it refers to micrometastasis in one regional lymph node; for colorectal cancer it refers to metastasis in one regional lymph node.
A general term that refers to a TNM finding of cancer metastases usually in a limited number of regional lymph nodes. The definition of N1b TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected; for cutaneous melanoma it refers to macrometastasis in one regional lymph node; for colorectal cancer it refers to metastasis in 2-3 regional lymph nodes.
Blindness is the condition of lacking visual perception due to physiological or neurological factors.
A rare variant of mycosis fungoides, characterized by the development of folds of lax skin in the axillae or groins. It has been reported in association with Hodgkin lymphoma. Morphologically, there is a dense granulomatous dermal atypical lymphocytic infiltrate, often associated with multinucleated giant cells. Destruction of elastic tissue is present. Most cases have an indolent clinical course. -- 2005
Weyers acrofacial dysostosis is an autosomal dominant condition with dental anomalies, nail dystrophy, postaxial polydactyly, and mild short stature. Ellis-van Creveld syndrome is a similar disorder, with autosomal recessive inheritance and the additional features of disproportionate dwarfism, thoracic dysplasia, and congenital heart disease (summary by Howard et al., 1997).
Book syndrome is a rare autosomal dominant ectodermal dysplasia syndrome reported in a Swedish family (25 cases from 4 generations), and one isolated case. The syndrome has characteristics of premolar aplasia, hyperhidrosis, and premature graying of the hair. Additional features reported in the isolated case include a narrow palate, hypoplastic nails, eyebrow anomalies, a unilateral simian crease, and poorly formed dermatoglyphics.
Toes appear swollen and plump owing to inflammation of the complete toe.
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of DAG1 (128239), collectively known as 'dystroglycanopathies' (summary by Godfrey et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
A WHO grade I large cystic tumor that occurs almost exclusively in infants, with a prominent desmoplastic stroma having a neuroepithelial population consisting mainly of neoplastic astrocytes. It involves the superficial cerebral cortex and leptomeninges, and often attaches to the dura. Although clinically it presents as large tumor, it generally has a good prognosis following surgical resection. (Adapted from WHO)
An abrupt decrease in the fetal heart rate below baseline that lasts 15 seconds to less than two minutes. The decrease from baseline fetal heart rate is greater than or equal to 15 beats per minute, and the time from onset to nadir of the deceleration is less than 30 seconds. Variable fetal heart rate decelerations that are associated with successive uterine contractions commonly have varying onsets, depths, and durations.
A decrease in the fetal heart rate below baseline lasting 2 to less than 10 minutes with a decrease from baseline that is greater than or equal to 15 beats per minute.
An acute myeloid leukemia in which the monoblasts represent 80% or more of the total cellular population. (WHO, 2001)
A rare neoplasm arising from tooth-forming tissues. It usually arises from the posterior mandible. It is characterized by the presence of an epithelial component, fibromyxoid stroma, and dentin formation. It is treated with enucleation and curettage. Recurrences may occur.
An ameloblastoma that presents as a unilocular cyst. It usually arises from the mandible.
A histologic variant of solid/multicystic ameloblastoma characterized by the presence of basal cells forming anastomosing strands and cords in a delicate stroma.
A histologic variant of solid/multicystic ameloblastoma characterized by the presence of odontogenic epithelial islands in a fibrotic stroma.
A solid/multicystic ameloblastoma with follicular pattern in which the central cells in the odontogenic epithelial islands show squamous differentiation.
A solid/multicystic ameloblastoma with follicular pattern in which the odontogenic epithelial islands contain granular cells.
An ameloblastoma with prominent desmoplastic stroma that causes compression of the neoplastic epithelial islands.
The relationship of the tooth in the jaw bone compared to the vertical position of zero degrees when viewed in an x-ray.
An individual who does not drink at the present time. This is a heterogeneous group comprising both lifelong teetotallers and ex-drinkers.
The oil extracted from the seeds of grapes. Grape seed oil is used in cooking and cosmetics and for medicinal purposes.
Conditions characterized by pain involving an extremity or other body region, HYPERESTHESIA, and localized autonomic dysfunction following injury to soft tissue or nerve. The pain is usually associated with ERYTHEMA; SKIN TEMPERATURE changes, abnormal sudomotor activity (i.e., changes in sweating due to altered sympathetic innervation) or edema. The degree of pain and other manifestations is out of proportion to that expected from the inciting event. Two subtypes of this condition have been described: type I; (REFLEX SYMPATHETIC DYSTROPHY) and type II; (CAUSALGIA). (From Pain 1995 Oct;63(1):127-33)
A chronic PELVIC PAIN characterized by pain deep in the buttock that may radiate to posterior aspects of the leg. It is caused by the piriformis muscle compressing or irritating the SCIATIC NERVE due to trauma, hypertrophy, inflammation or anatomic variations.
Pain due to a stimulus that does not normally provoke pain.
A sense of discomfort or distress that is spasmodic or clenching.
An intense sensation of discomfort or distress that feels like being cut apart.
A sense of discomfort or distress that is squeezing or excessively compressing.
Anxiety related to the execution of a task. (Campbell's Psychiatric Dictionary, 9th ed.)
A convex curvature of the spine that occurs when an individual thrusts forward the shoulders and pulls back the abdomen.
An indication that there was not enough sample available.
A specimen that consists of or contains excessive amounts of fat and fatty substances.
A specimen that exhibits a yellowish pigmentation due to jaundice.
Bleeding into the cortex or white matter of a cerebral lobe
Bleeding within the subcortical regions of cerebral hemispheres (BASAL GANGLIA). It is often associated with HYPERTENSION or ARTERIOVENOUS MALFORMATIONS. Clinical manifestations may include HEADACHE; DYSKINESIAS; and HEMIPARESIS.
Infection of the FRONTAL BONE often as a complication of FRONTAL SINUSITIS or trauma to the frontal bone and skull. It is characterized by subperiosteal abscess with OSTEOMYELITIS.
Aplastic anemia caused by excessive absorption of radiation by the bone marrow.
A condition in which a person has reduced protein production from two of the four alpha-globin alleles.
Methemoglobinemia that is caused by exposure to certain drugs (xylocaine and benzene).
Less than the necessary amount of the enzyme that converts methemoglobin into hemoglobin.
IGHD3 is characterized by agammaglobulinemia and markedly reduced numbers of B cells, short stature, delayed bone age, and good response to treatment with growth hormone (summary by Conley et al., 1991). For general phenotypic information and a discussion of genetic heterogeneity of IGHD, see 262400.
WHIM syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia, and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis. The susceptibility to HPV is disproportionate compared with other immunodeficiency conditions (summary by Hernandez et al., 2003).
Elevated bilirubin levels in the blood of a newborn infant. It is a normal response due to the limited ability to excrete bilirubin until the maturation of the neonatal liver is complete.
A collection of blood around the kidney.
A renal disorder characterized by glomerular damage due to ischemia. It leads to progressive deterioration of renal function.
Renal hypouricemia is characterized by impaired uric acid reabsorption at the apical membrane of proximal renal tubule cells. The syndrome is not lethal and may be asymptomatic. However, it is accompanied by nephrolithiasis and exercise-induced acute renal failure in about 10% of patients (Ichida et al., 2008). Genetic Heterogeneity of Renal Hypouricemia See also RHUC2 (612076), which is caused by mutation in the SLC2A9 gene (606142).
Glomerulonephritis in the context of cryoglobulinemia.
Hematuria that is visible upon inspection of the urine.
An abdominal mass formed by bleeding into a follicular ovarian cyst or corpus luteum cyst.
Frequent painful contractions prior to 37 weeks of gestation without cervical change.
A focus of retroplacental thrombus variably extending into the intervillous space, often with peripheral villous compression. The clot may be wholly or minimally laminated reflecting age.
Excessive blood loss between 24 hours after delivery through four weeks that requires intervention.
A metabolic disorder characterized by deficiency of high density (alpha) lipoprotein in the blood.
Vibratory urticaria is a condition in which exposing the skin to vibration, repetitive stretching, or friction results in allergy symptoms such as hives (urticaria), swelling (angioedema), redness (erythema), and itching (pruritus) in the affected area. The reaction can be brought on by towel drying, hand clapping, running, a bumpy ride in a vehicle, or other repetitive stimulation. Headaches, fatigue, faintness, blurry vision, a metallic taste in the mouth, facial flushing, and more widespread swelling (especially of the face) can also occur during these episodes, especially if the stimulation is extreme or prolonged. The reaction occurs within a few minutes of the stimulation and generally lasts up to an hour. Affected individuals can have several episodes per day.
A rare disorder which affects the volar surfaces of fingers. Clinical signs include recurrent, spontaneous or post-traumatic bruising of fingers. The clinical course of the resultant hematoma usually follows a pattern of resolution within days.
A form of diffuse palmoplantar keratoderma that occurs between the ages of 5 and 15 and may be associated with the subsequent development of esophageal cancer
A rare, congenital disorder of the eccrine sweat ducts that presents as grouped keratotic papules and plaques with a linear distribution and/or multiple punctate pits filled with tiny keratotic plugs resembling comedones. The lesion are usually located on the acral portion of a limb.
Symmetric ringed creases around the extremities which disappear later in life. They are reminiscent of these of the mascot of the tire manufacturer, Michelin, hence the name of the syndrome. Associated abnormalities vary and may include facial dysmorphism, upslanting palpebral fissures, hypertelorism, cleft palate, genital anomalies, mild developmental delay, ureterocele, smooth muscle hamartoma, nevus lipomatosus, Laron syndrome (dwarfism and high growth hormone and low somatomedin activity), and other defects.
A type of retinal neovascularization that affects the periphery of the retina.
A type of retinal hemorrhage that is located within the nerve fiber layer (NFL) of the retina and that exhibits a characteristic flame shape which results from constraints by the structure of the NFL (axons of the ganglion cells).
Accumulation of blood located in the retina's inner nuclear and outer plexiform layers, and having a dot-like or blot-like shape. THe shape results from intraretinal compression, restricting the hemorrhages within a specific location.
Sensory functions relating to determining the location of the source of sound.
Pain associated with OBSTETRIC LABOR in CHILDBIRTH. It is caused primarily by UTERINE CONTRACTION as well as pressure on the CERVIX; BLADDER; and the GASTROINTESTINAL TRACT. Labor pain mostly occurs in the ABDOMEN; the GROIN; and the BACK.
Corneal edema of inflammatory origin associated with contact lens wear and morphologically characterized by presence of epithelial microcysts. Microcysts are small (typically 10-50 microns in diameter), clear, irregularly shaped high refractive inclusions that form in the basal layers of the epithelium and move towards the anterior surface of the cornea, surrounding epithelial haze. The cause of microcytic edema is related to the physical presence of contact lenses and possibly a mechanical effect of lens wear.
Abnormal accumulation of fluid and swelling of the stroma of cornea.
An electrocardiographic finding of ST and T wave changes consistent with impaired myocardial perfusion.
A neoplasm that affects the cerebellopontine angle. Representative examples include vestibular schwannoma and meningioma.
A classification system grouping neoplasms according to their cellular characteristics.
A neoplasm composed of basal cells that remains localized and does not metastasize to other anatomic sites.
A benign, borderline, or malignant epithelial tumor of the female reproductive system characterized by the presence of glands and/or cysts lined by neoplastic cells that resemble endometrial cells.
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia in the vagus nerve. Patients may present with a slow growing, painless mass in the neck, hoarseness, vocal cord paralysis, and dysphagia.
A benign or malignant middle ear paraganglioma arising from paraganglia around the tympanum. Signs and symptoms include a mass behind the tympanum, tinnitus, and conductive hearing loss.
A benign melanocytic nevus with a halo appearance.
A benign neoplasm composed of mesenchymal stromal cells without evidence of cellular atypia.
A benign transitional cell neoplasm that arises from the ovary and is composed of a fibrotic stroma and nests of transitional cells without evidence of atypia. There is no evidence of invasion.
A central nervous system neoplasm with neuronal and, less consistently, glial differentiation.
A rare variant of malignant peripheral nerve sheath tumor. It is characterized by the presence of malignant cells that contain melanin.
A ureterocele in which some portion of the ureterocele is situated permanently at the bladder neck or in the urethra. The orifice may be situated in the bladder, at the bladder neck, or in the urethra. (Adapted from Glassberg KI, Braren V, Duckett JW, Jacobs EC, King LR, Lebowitz RL et al. Suggested terminology for duplex systems, ectopic ureters and ureteroceles. J Urol 1984; 132(6):1153-1154.)
A type of pilosebaceous hamartoma characterized by basal cell epitheliomata, epidermoid cysts and comedones, and epidermal atrophy.
A benign, small and slightly elevated brown or black skin lesion with usually well-demarcated borders. It is characterized by the presence of a melanocytic proliferation resulting in the formation of uniform cellular nests. Sometimes the clinical and morphologic features may be difficult to distinguish from melanoma.
A morphologic qualifier indicating that a cancerous lesion is well differentiated.
A primary tumor TNM finding indicating that there is no evidence of primary tumor.
A clinical and/or pathologic primary tumor TNM finding indicating that the cancer is limited to the site of growth.
A general term that refers to a TNM finding of primary tumor growth beyond the level of in situ cancer, minimal subepithelial invasion, or minimal greatest diameter. The definition of T2 TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to primary tumor that is more than 2.0 cm, but not more than 5.0 cm in greatest dimension; for cutaneous melanoma it refers to primary tumor that is 1.01 to 2 mm in thickness, with or without ulceration; for colorectal cancer it refers to primary tumor with invasion into the muscularis propria; and for bladder cancer it refers to primary tumor with invasion into the muscle layer.
A clinical and/or pathologic primary tumor TNM finding usually indicating that the cancer is locally invasive, without infiltration of adjacent structures.
A general term that refers to a TNM finding of a primary tumor limited to the site of growth. The definition of T1a TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to a primary tumor that is more than 0.1cm, but not more than 0.5 cm in greatest dimension; for kidney cancer it refers to a primary tumor that is 4 cm or less in greatest dimension; and for thyroid cancer it refers to a primary tumor that is 1 cm or less in greatest dimension.
A general term that refers to a TNM finding of a primary tumor growth beyond the level of in situ cancer, minimal subepithelial invasion, or minimal greatest diameter. The definition of T2a TNM finding depends on the specific type of cancer that it refers to; for example, for kidney cancer it refers to a primary tumor that measures more than 7 cm but less than or equal to 10 cm in greatest dimension, and is limited to the kidney; for bladder cancer it refers to a primary tumor that invades the superficial muscularis propria (inner half); for cervical cancer it refers to a primary tumor that invades beyond the uterus but not to the pelvic wall or to the lower third of vagina and there is no parametrial invasion.
A general term that refers to a TNM finding of a primary tumor growth beyond the level of in situ cancer, minimal subepithelial invasion, or minimal greatest diameter. The definition of T2b TNM finding depends on the specific type of cancer that it refers to; for example, for kidney cancer it refers to a primary tumor that measures more than 10 cm in greatest dimension, and is limited to the kidney; for bladder cancer it refers to a primary tumor that invades the deep muscularis propria (outer half); for cervical cancer it refers to a primary tumor that invades beyond the uterus but not to the pelvic wall or to the lower third of vagina and there is parametrial invasion.
A general term that refers to a TNM finding of a primary tumor usually indicating that the cancer is locally invasive. The definition of T3a TNM finding depends on the specific type of cancer that it refers to; for example, for kidney cancer it refers to a primary tumor that grossly extends into the renal vein or its segmental (muscle containing) branches or the tumor invades perirenal and/or renal sinus fat but does not extends beyond Gerota's fascia; for cervical cancer it refers to a primary tumor that involves the lower third of vagina, without extension to pelvic wall; for liver cancer it refers to the presence of multiple tumors measuring more than 5 cm in greatest dimension.
A general term that refers to a TNM finding of a primary tumor with direct invasion of adjacent structures. The definition of T4b TNM finding depends on the specific type of cancer that it refers to; for example, for bladder cancer it refers to a primary tumor that invades the pelvic wall and abdominal wall; for gastric cancer it refers to a primary tumor that invades adjacent structures; for colorectal cancer it refers to a primary tumor with direct invasion or adherence to other organs or structures.
Sensory functions relating to determining whether the sound is coming from the right or left side.
A term that refers to a TNM finding of a primary tumor microscopically defined as carcinoma in situ.
A group of hemolytic anemias that result from either the deficiency or overproduction of several enzymes involved in metabolizing nucleotides.
Bleeding into the thick layer of immature cells under the ependymal lining at the ventrolateral aspect of the lateral cerebral ventricles of a newborn.
Bleeding into the lateral cerebral ventricles of a newborn infant without acute ventricular dilatation.
Bleeding into the lateral cerebral ventricles of a newborn infant with ventricular dilatation directly attributable to the acute bleeding.
Abnormally dark tarry feces containing blood, usually due to gastrointestinal bleeding or swallowed maternal blood in neonates.
Hemolytic Anemia: anemia resulting from active destruction of red blood cells -- documented by reticulocytosis, indirect hyperbilirubinemia, and sometimes hemoglobinemia.
The cessation of breathing in premature infants that lasts for more than 15-20 seconds.
Blood glucose concentration above the upper limit of established reference ranges in a newborn.
Bleeding between the scalp and the periosteum.
Bleeding within the skull of a newborn infant occurring around the time of birth.
Bleeding within the cerebral ventricles in a preterm infant.
Bleeding into the thick layer of immature cells under the ependymal lining at the ventrolateral aspect of the lateral cerebral ventricles occurring around the time of birth.
A hemorrhage that involves the subependymal region, the lateral cerebral ventricles and the brain tissue occurring around the time of birth.
A clinical and/or pathologic primary tumor TNM finding indicating direct invasion of adjacent structures by cancer.
A malignant B-cell lymphoproliferative process affecting the blood, bone marrow, and spleen. The B-prolymphocytes are medium-sized, round lymphoid cells with prominent nucleoli. The B-prolymphocytes must exceed 55% of lymphoid cells in the blood. Cases of transformed chronic lymphocytic leukemia (CLL) and CLL with increased prolymphocytes are excluded. The prognosis is poor. (WHO, 2001)
A specimen that has undergone the destruction of red blood cells followed by the release of the hemoglobin.
A tumor shaped like a small mushroom, with its stem attached to the epithelial layer (inner lining) of an organ.
A carcinoma of the endometrium, the mucous lining of the uterus.
A benign, borderline, or malignant epithelial tumor that arises from the ovary and is characterized by the presence of papillary proliferations. Representative examples include surface papilloma, borderline serous surface papillary tumor, and serous surface papillary adenocarcinoma.
A benign, borderline, or malignant epithelial tumor of the ovary characterized by the presence of neoplastic epithelial cells that, in well differentiated tumors, resemble the epithelial cells of the fallopian tube and, in poorly differentiated tumors, show anaplastic features. Approximately thirty to fifty percent of the tumors are bilateral. Grossly, the better differentiated tumors consist of cystic masses, usually unilocular, containing a clear but sometimes viscous fluid. Papillary formations are often present. The more malignant tumors tend to be solid and invasive, with areas of necrosis and hemorrhage.
A term that refers to vascular neoplasms with a prominent hemangiopericytic growth pattern.
A benign, intermediate, or malignant cartilaginous matrix-producing neoplasm. Representative examples include osteochondroma, chondroblastoma, and chondrosarcoma.
A benign or malignant soft tissue neoplasm arising exclusively from the synovial membrane. Examples include the diffuse giant cell tumor of tendon sheath, localized giant cell tumor of tendon sheath, and malignant giant cell tumor of tendon sheath.
For cerebral dominance, the presence of right dominance or preference for some functions (eye dominance, foot preference, hand preference), and left dominance or preference for others
A cognitive disorder characterized by an impaired ability to comprehend written and printed words or phrases despite intact vision. This condition may be developmental or acquired. Developmental dyslexia is marked by reading achievement that falls substantially below that expected given the individual's chronological age, measured intelligence, and age-appropriate education. The disturbance in reading significantly interferes with academic achievement or with activities of daily living that require reading skills. (From DSM-IV)
A pathological increase in the effort and frequency of breathing movements.
Pain in the chest unrelated to a heart disorder.
The diagnosis of severe breath-holding spells (BHS) in childhood is based on a distinctive and stereotyped sequence of clinical events beginning with a provocation resulting in crying or emotional upset that leads to a noiseless state of expiration accompanied by color change and ultimately loss of consciousness and postural tone (Lombroso and Lerman, 1967; DiMario, 1992). Two clinical types are recognized based on the child's coloration (cyanotic or pallid) during these events. Most children experience the cyanotic type, although some experience mixed types. BHS is an involuntary, nonvolitional, reflexic, nonepileptic paroxysmal phenomenon of childhood. The episodes occur during full expiration despite its misnomer. Autonomic dysregulation has been hypothesized as an underlying mechanism that results in loss of consciousness (Hunt, 1990; DiMario and Burleson, 1993; Dimario et al., 1998).
A deviation from normal of the mean corpuscular volume, or mean cell volume (MCV) of red blood cells, usually taken to be 80 to 100 femtoliters.
A laboratory test indicating increased levels of amylase in the serum.
An abnormality of the partial pressure of oxygen or carbon dioxide in the arterial blood.
An abnormality detectable by sonography of the heart (echocardiography).
Any abnormality of the electrical responses of various cell types in the retina as measured by electroretinography. [HPO:probinson]
Abnormal results of investigations using electromyography (EMG).
Any anomaly measure by pulmonary function testing, which includes spirometry, measures of diffusing capacity, and plethysmography.
An abnormal reduction on the vital capacity, which is defined as the total lung capacity (volume of air in the lungs at maximal inflation) less the residual volume (i.e., volume of air in the lungs following maximal exhalation) of the lung. [HPO:probinson]
A finding indicating the presence of abnormal cervical cells in a Pap smear.
A variation from the normal set of chromosomes characteristic of a species.
An indication that a subject was found in a deceased state.
An increased concentration of alpha-fetoprotein.
Academic achievement less than that expected based on one's scholastic aptitude score or individual intelligence.
A bone disorder involving ossification centers (EPIPHYSES) of the VERTEBRAL COLUMN.
Defect or defects of the morphogenesis of the aorta and pulmonary arteries.
Indicates that human immunodeficiency virus has not been detected in a sample.
Treatment designed to help prevent a relapse of a disease following the successful primary treatments (INDUCTION CHEMOTHERAPY and CONSOLIDATION CHEMOTHERAPY) with a long-term low-dose drug therapy.
The complete expulsion or extraction from the mother of a fetus, irrespective of the duration of pregnancy, which, after such expulsion or extraction, breathes or shows any other evidence of life, such as beating of the heart, pulsation of the umbilical cord, or definite movement of voluntary muscles.
A morphologic finding indicating the presence of nucleated red cells in the peripheral blood.
brand name of zolpidem, a drug used to treat insomnia
Blood flow through a region of the lung in which little or no ventilation takes place, resulting in reduced oxygenation of the blood leaving the lungs.
A malignant neoplasm that affects the renal parenchyma but not the pelvis.
A malignant neoplasm that has spread to the small intestine from another anatomic site.
A malignant neoplasm that has spread to the liver from another (primary) anatomic site. Such malignant neoplasms may be carcinomas, lymphomas, melanomas, or sarcomas.
Any form of anemia that results from the absence of, or the defective action of, any enzyme.
A broad classification of inherited disorders presenting at birth that affect both the cell-mediated and humoral aspects of the immune response. Circulating numbers of B lymphocytes, T lymphocytes and NK cells are variable but where present do not function properly. Susceptibility to infection is the primary concern.
A generalized tonic-clinic seizure, characterized by loss of consciousness. This type of seizure may be preceded by an aura and is frequently followed by a period of confusion and lethargy (post-ictal state).
A focal lesion of a single peripheral nerve. Damage to a sensory nerve is accompanied by sensory impairment of all modalities in the affected anatomic distribution.
A non-neoplastic or neoplastic disorder affecting the inner ear. Causes are inner ear infections, head injuries, and neoplasms (e.g., acoustic schwannoma). Symptoms include dizziness, imbalance, nausea, and vision problems.
A disorder of the teeth arising during odontogenesis.
A blistering disorder characterized by linear deposition of IgA at the dermoepidermal junction.
Dermatitis caused by an allergic reaction to ingested food.
Thickening of the epidermal layer of the skin.
Discrepancy between the lengths of the lower or upper extremities.
Retroperitoneal fibrosis is a disorder in which inflammation and extensive scar tissue (fibrosis) occur in the back of the abdominal cavity, behind (retro-) the membrane that surrounds the organs of the digestive system (the peritoneum). This area is known as the retroperitoneal space. Retroperitoneal fibrosis can occur at any age but appears most frequently between the ages of 40 and 60.The inflamed tissue characteristic of retroperitoneal fibrosis typically causes gradually increasing pain in the lower abdomen, back, or side. Other symptoms arise from blockage of blood flow to and from various parts of the lower body, due to the development of scar tissue around blood vessels. The fibrosis usually develops first around the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Additional blood vessels including the inferior vena cava, which returns blood from the lower part of the body to the heart, may also be involved. Obstruction of blood flow to and from the legs can result in pain, changes in color, and swelling in these limbs. Impairment of blood flow in the intestines may lead to death (necrosis) of intestinal tissue, severe pain, and excessive bleeding (hemorrhage). In men, reduced blood flow back toward the heart (venous flow) may cause swelling of the scrotum.Because the kidneys are located in the retroperitoneal space, retroperitoneal fibrosis may result in blockage of the ureters, which are tubes that carry urine from each kidney to the bladder. Such blockages can lead to decreased or absent urine flow and kidney failure. When the kidneys fail, toxic substances build up in the blood and tissues, leading to nausea, vomiting, weight loss, itching, a low number of red blood cells (anemia), and changes in brain function.
An intraepithelial lesion of the vulvar squamous epithelium that represents the clinical and morphological manifestation of a productive HPV infection. Low grade refers to the associated low risk of concurrent or future cancer. (WHO, 2014)
An intraepithelial lesion of the vulvar squamous epithelium that carries a significant clinical risk of invasive cancer development if not treated. Almost all these lesions contain HPV-16. (WHO, 2014)
Extraction of a fetus through the cervix using destructive surgical techniques.
A condition characterized as a temporary autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatigue in a newborn infant.
A primary or metastatic malignant neoplasm affecting the major salivary glands. Representative examples include carcinoma, lymphoma, and sarcoma.
A primary or metastatic malignant neoplasm that affects the postcricoid region.
A primary or metastatic malignant neoplasm involving the cervical region of the esophagus.
A primary or metastatic malignant neoplasm involving the abdominal region of the esophagus.
A primary or metastatic malignant neoplasm that affects the appendix. Representative examples include carcinoma and lymphoma.
A malignant neoplasm that affects the middle ear. Representative examples include adenocarcinoma and squamous cell carcinoma.
A malignant neoplasm that affects the labia majora.
A malignant neoplasm that affects the labia minora.
The upper, convex surface of the bladder.
The aspect of the bladder wall that is located on the side.
A primary or metastatic malignant neoplasm involving the structures of the eye (conjunctiva, cornea, uvea, retina), the lacrimal gland, and the eyelid. Representative examples include melanoma, carcinoma, lymphoma, and retinoblastoma.
Abnormal malignant growth of the cells that comprise cranial nerve I. This can lead to difficulties with the sense of smell. Since taste and smell are intimately linked in terms of the enjoyment of food, a deficiency in the ability to smell can lead to decreased food intake with possible malnutrition.
A primary or metastatic malignant neoplasm affecting the pituitary gland. Representative examples include functioning or non-functioning carcinomas arising from the anterior lobe of the pituitary gland, chordomas, chondrosarcomas, and metastatic carcinomas from the breast, lung, and gastrointestinal tract.
A non-metastasizing neoplasm that arises from the parotid gland. Representative examples include Warthin tumor, monomorphic adenoma, pleomorphic adenoma, and lipoma.
A non-metastasizing neoplasm that arises from the major salivary glands. Representative examples include Warthin tumor, monomorphic adenoma, and pleomorphic adenoma.
A non-metastasizing neoplasm arising from the wall of the cecum.
A non-metastasizing neoplasm arising from the appendix.
A non-metastasizing neoplasm arising from the wall of the rectum.
A non-metastasizing neoplasm arising from the wall of the duodenum.
A non-metastasizing neoplasm that arises from the extrahepatic bile ducts.
A non-metastasizing neoplasm that arises from the retroperitoneum.
A non-metastasizing neoplasm that arises from the peritoneal cavity. Representative examples include adenomatoid tumor and disseminated peritoneal leiomyomatosis.
A non-metastasizing neoplasm that arises from the kidney. Representative examples include cystic nephroma, metanephric adenoma, oncocytoma, and urothelial papilloma of the renal pelvis.
A non-metastasizing neoplasm that arises from the ciliary body. Representative examples include leiomyoma and adenoma of the ciliary epithelium.
An epibulbar dermoid is a benign tumor typically found at the junction of the cornea and sclera (limbal epibullar dermoid).
A primary, slow growing, noninvasive neoplasm of the brain. In children, astrocytomas of the cerebellum represent relatively common benign brain neoplasms. In adults meningiomas, neurilemomas and pituitary tumors comprise the majority of benign tumors.
A neoplasm without metastatic potential arising from the anterior or the posterior lobe of the pituitary gland. The vast majority are adenomas.
An enlarged lymph node. Causes include viral and bacterial infections and cancers that affect the lymph nodes.
An abnormality in voluntary or involuntary eye movements or their control.
An infectious process affecting the conjunctiva.
A benign or malignant neoplasm that affects the heart and/or vessels. Representative examples of benign neoplasms include atrial myxoma, hemangioma, and lymphangioma. Representative examples of malignant neoplasms include pericardial malignant mesothelioma and angiosarcoma.
A finding of increased blood pressure; not necessarily hypertensive disorder
A condition of high blood pressure without resulting clinical disorders.
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
An area of irritated or swollen skin covering the entire surface of the skin.
A condition in which body mass index falls between 25 and 29.9.
A non-metastasizing neoplasm arising from any part of the digestive system.
A primary or metastatic malignant neoplasm involving the nervous system.
Abnormal growth of cells in the nervous system without evidence of malignant characteristics. Unlike other organ systems, tumors in the central nervous system can have benign histological characteristics but still have life threatening effects due to their location within the neuraxis (e.g., brainstem gliomas).
An abnormality of the nervous system that is present at birth or detected in the neonatal period.
Evidence that the victim is no longer hurt or exploited
Protection of self and/or dependent others from abuse
Extent of healing of psychological injuries due to abuse
Extent of control of monetary and legal matters following financial exploitation
Extent of healing of physical injuries due to abuse
Extent of healing of physical and psychological injuries due to sexual abuse or exploitation
Personal actions to reconcile significant changes in health circumstances
Self-initiated actions to promote optimal wellness, recovery, and rehabilitation
Infant attachment to and sucking from the mother's breast for nourishment during the first 3 weeks of breastfeeding
Maternal establishment of proper attachment of an infant to and sucking from the breast for nourishment during the first 3 weeks of breastfeeding
Continuation of breastfeeding from establishment to weaning for nourishment of an infant/toddler
Progressive discontinuation of breastfeeding of an infant/toddler
Adaptive response of family caregiver when the care recipient is moved to an institution
Emotional well-being of a family care provider while caring for a family member
Preparedness of a caregiver to assume responsibility for the health care of a family member in the home
Severity of disturbances in the lifestyle of a family member due to caregiving
Positive interactions and connections between the caregiver and care recipient
Caregiver actions to provide personal and health care services for an individual needing assistance
Caregiver actions to arrange and oversee required care for an individual needing assistance
Physical well-being of a family care provider while caring for a family member
Severity of biopsychosocial pressure on a family care provider caring for another over an extended period of time
Milestones of physical, cognitive, and psychosocial progression by 2 months of age
Milestones of physical, cognitive, and psychosocial progression by 4 months of age
Milestones of physical, cognitive, and psychosocial progression by 6 months of age
Milestones of physical, cognitive, and psychosocial progression by 12 months of age
Milestones of physical, cognitive, and psychosocial progression by 2 years of age
Milestones of physical, cognitive, and psychosocial progression by 3 years of age
Milestones of physical, cognitive, and psychosocial progression by 4 years of age
Unobstructed, unidirectional blood flow at an appropriate pressure through large vessels of the systemic and pulmonary circuits
Personal actions to adjust thoughts, feelings, and behaviors to actual or impending loss
Personal conviction that one can carry out a given health behavior
Personal conviction that one can influence a health outcome
Personal conviction that one has adequate means to carry out a health behavior
Personal conviction that a threatening health problem is serious and has potential negative consequences for lifestyle
Personal attitudes and commitment to health behaviors as lifestyle priorities
Personal actions to sustain or increase wellness
Severity of compromise in physiological functioning due to impaired physical mobility
Severity of compromise in psycho-cognitive functioning due to impaired physical mobility
Personal actions to obtain immunization to prevent a communicable disease
Severity of signs and symptoms of infection
Extent of understanding conveyed about lactation and nourishment of an infant through breastfeeding
Extent of understanding conveyed about a specific disease process and potential complications
Extent of understanding conveyed about energy conservation techniques
Extent of understanding conveyed about relevant health care resources
Extent of understanding conveyed about the safe use of medication
Extent of understanding conveyed about risk reduction and prevention of unintentional injuries to self
Extent of understanding conveyed about physical activity recommended by a health professional for a specific condition
Extent of understanding conveyed about controlling the use of addictive drugs, toxic chemicals, tobacco, or alcohol
Extent of understanding conveyed about a specific treatment regimen
Extent of physical, emotional, and spiritual healing following the cessation of substandard care
Arousal, orientation, and attention to the environment
Ability of the central nervous system to coordinate skeletal muscle activity for body movement
Ability of the autonomic nervous system to coordinate visceral and homeostatic functions
Adequacy of blood volume ejected from the left ventricle to support systemic perfusion pressure
Body fluid components and chemical indices of nutritional status
A measurement of the thickness of a pinch of skin situated below or on the underside of the scapula.
The amount of an individual's total body mass that is fat, expressed as a percent.
Extent to which nutrients provide cellular energy
The ability to sustain an activity over a period of time.
Amount of food and fluid taken into the body over a 24-hour period
Severity of observed or reported disruptive effects of chronic pain on daily functioning
Normal physiological changes that occur with the natural aging process
Normal physical changes in the female that occur with the transition from childhood to adulthood
Change in the sound and/or speed of the voice. Causes include laryngeal polyp, laryngitis, laryngeal carcinoma, throat carcinoma, Parkinson's disease, multiple sclerosis, stroke, hypothyroidism, oral surgery, tracheostomy, tracheal injury, and laryngeal injury.
Normal physical changes in the male that occur with the transition from childhood to adulthood
Use of activities by a child to foster age-appropriate social and physical skills that are enjoyable and entertaining
The subjective measurement of an individual's sense of well-being and ability to enjoy life. The concept holds varying meanings for different people and may evolve over time. For some individuals it implies autonomy, empowerment, capability, and choice; for others, security, social integration, or freedom from stress or illness.
Alveolar exchange of carbon dioxide and oxygen to maintain arterial blood gas concentrations
Diminished ability to perform independent movement
Personal actions to prepare and ingest food and fluid independently with or without assistive device
Personal actions to dress self independently with or without assistive device
Personal actions to cleanse own body independently with or without assistive device
Personal actions to maintain own personal cleanliness and kempt appearance independently with or without assistive device
Personal actions to administer parenteral medications to meet therapeutic goals independently with or without assistive device
Severity of change in health status and social functioning due to substance addiction
Subjective feeling of tiredness characterized by a lack of energy and motivation that persists for six months or longer.
Structural intactness and normal physiological function of skin and mucous membranes
Adequacy of blood flow through the small vessels of the abdominal viscera to maintain organ function
Adequacy of blood flow through the coronary vasculature to maintain heart function
Adequacy of blood flow through the cerebral vasculature to maintain brain function
Adequacy of blood flow through the small vessels of the extremities to maintain tissue function
Adequacy of blood flow through pulmonary vasculature to perfuse alveoli/capillary unit
A term used to describe the state or condition of the completeness of the vital signs data.
Desire, determination, and effort to survive
Extent of regeneration of cells and tissues following intentional closure
Extent of regeneration of cells and tissues in an open wound
Extrauterine integration of physiological and behavioral function by the infant born 24 to 37 (term) weeks gestation
Severity of signs and symptoms of long-term anguish due to a distressing event, injury, or loss
Extent of understanding conveyed about the promotion and protection of health
A cardiac myxoma arising from the left atrium.
A cardiac myxoma arising from the right atrium.
A pocket of pus located within a region of a tooth.
An extranodal lymphoma that arises from the colon. The majority are B-cell non-Hodgkin lymphomas.
Lung parenchymal involvement with lymphoma.
A bulge or ballooning in the wall of the left ventricle of the heart.
The trisodium salt form of calcium diethylene triamine pentaacetate (Ca-DTPA or pentetate calcium) with chelating activity. Upon administration, Ca-DTPA loses the Ca ion to form stable chelates with metal ions because DTPA has a higher affinity for heavy metal ions than for Ca ions. Specifically, this agent is able to bind to and form strong complexes with radioactive plutonium, americium, and cerium after internal contamination with any of these radionuclides thereby increasing their excretion.
ENTEROCOLITIS with extensive ulceration (ULCER) and NECROSIS. It is observed primarily in LOW BIRTH WEIGHT INFANT.
An aggressive form of chronic hepatitis involving extensive liver damage and cell injury beyond the portal tract.
The levoisomer of nordefrin, a synthetic catecholamine and norepinephrine derivative with sympathomimetic and antihypertensive effects. Levonordefrin's antihypertensive effect is exerted through activation of alpha 2-adrenergic receptors in the cardiovascular control center of the CNS thereby suppressing the sympathetic output from the brain and subsequently lowering blood pressure. Levonordefrin binds to and activates peripheral alpha 2- adrenergic receptors, thereby causing vasoconstriction.
Necrosis of bone due to an inadequate blood supply.
Focal benign glandular hyperplasia in the prostate gland.
Pattern of recurring polysymptomatic somatic complaints resulting in medical treatment or impaired daily function. Usually begins before age 30 and extends over a period of years.
An abnormal connection between arteries and veins characterized by the absence of intervening capillaries in the liver.
A circumscribed inflammatory and necrotic erosive lesion in the mucosa surface of the ileum.
An area of fat accumulation at the backof the next in the form of a hump.
A normal variant in which the testicle may move freely between the scrotum and the groin.
Tiny deposits of calcium in tissue. In the breast they can be seen using mammography, and if found in clusters may be indicative of breast cancer.
reduction of oxygen supply to tissues in newborns that is below physiological levels.
A condition in which a woman suffers from severe depression, irritability, and tension before MENSTRUATION. Premenstrual dysphoric disorder (PMDD) may involve a wide range of physical or emotional symptoms, which are more severe and debilitating than those seen with premenstrual syndrome (PMS), and which include at least one mood-related symptom. Symptoms usually stop when, or shortly after, menstruation begins.
A subtype of delusional disorder applied when no one delusional theme (such as grandiose, jealous, persecutory) predominates.
Psychotic reaction occurring after childbirth.
Obstructive sleep apnea is a common, chronic, complex disease associated with serious cardiovascular and neuropsychologic sequelae and with substantial social and economic costs (Palmer et al., 2003).
A condition associated with multiple episodes of sleep apnea which are distinguished from obstructive sleep apnea (SLEEP APNEA, OBSTRUCTIVE) by the complete cessation of efforts to breathe. This disorder is associated with dysfunction of central nervous system centers that regulate respiration.
Cyst of the nerve roots filled with cerebrospinal fluid, usually located in the sacral area of the spine.
A type of hemolytic anemia in which the Coombs test is positive.
Hereditary pyropoikilocytosis was originally described by Zarkowsky et al. (1975) as a distinct hemolytic anemia characterized by microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells. HPP is a subset of hereditary elliptocytosis (see 611804) due to homozygous or compound heterozygous mutations in spectrin leading to severe disruption of spectrin self-association (review by An and Mohandas, 2008).
Swelling of lymph nodes within the mediastinum, the central compartment of the thoracic cavities that contains the heart and the great vessels, the esophagus, and trachea and other structures including lymph nodes.
The swallowing of an item not intended for consumption.
Abnormally slow pace of regaining CONSCIOUSNESS after general anesthesia (ANESTHESIA, GENERAL) usually given during surgical procedures. This condition is characterized by persistent somnolence.
Alteration of any condition or process in an offspring that results form the effect of a carcinogen in a parent.
Gastroenteritis resulting from an infection with cryptosporidium.
Gastroenteritis that is caused by Cryptosporidium.
.Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Knee clonus can be tested by rapidly pushing the patella towards the toes.
An abnormal reduction on the vital capacity, which is defined as the total lung capacity (volume of air in the lungs at maximal inflation) less the residual volume (i.e., volume of air in the lungs following maximal exhalation) of the lung.
An increase in the fraction of the forced vital capacity that is exhaled in a specific number of seconds.
A decrease in the fraction of the forced vital capacity that is exhaled in a specific number of seconds.
An increase of the greatest rate of flow that can be achieved during forced expiration beginning with the lungs fully inflated.
Decreased expiratory peak flow measurement achieved during forced expiration that primarily reflects changes in upper airway conductance and may be of limited use in evaluation of changes in peripheral airway conductance. Evaluation of peak flow performance is subjective, and, therefore, acceptability criteria are lacking. Because the maneuver is effort and volume dependent, the patient must be encouraged to perform as vigorously as clinically feasible. The results of subjective evaluation may be difficult to interpret consistently. A validated dyspnea rating scale may be useful.
The measurement of the mean left arterial pressure, as measured by a catheter introduced into the distal pulmonary artery, is normal.
Pulmonary capillary wedge pressure (PCWP) above 15mmHg.
The measurement of the mean left pulmonary arterial pressure, as measured by a catheter introduced into the distal pulmonary artery, is low.
An anomaly of the jugular venous pressure. The internal jugular veins, being continuous with the superior vena cava, provide a visible measure of the degree to which the systemic venous reservoir is filled. The vertical height above the right atrium to which they are distended and above which they are in a collapsed state provides an imperfect reflection of the right atrial pressure.
A finding of an increase in the jugular venous pressure, as measured by the height of the mean jugular venous waveform above the right atrium.
Impairment in the filling of the ventricles during diastole. Causes include hypertrophic and restrictive cardiomyopathies, coronary artery disease, chronic high blood pressure, aortic stenosis, and aging.
An electrocardiographic finding of an abnormally short PR interval. Thresholds for different age, gender, and patient populations exist. (CDISC)
An electrocardiographic anomaly in which the ST segment is observed to be located superior to the isoelectric line.
An electrocardiographic anomaly in which the ST segment is observed to be located inferior to the isoelectric line.
An electrocardiographic finding of an inversion of the T wave from the expected axis.
A peeling off or loss of epidermis, as in sunburn, postscarlatinal peeling, or toxic epidermal necrolysis.
Emesis and queasiness occurring after anesthesia.
Incomplete maturation or aberrant formation of the male gametes.
A finding indicating decreased tissue sensitivity to a hormone.
An anomaly in the amount of force per unit area exerted by the intraocular fluid within the eye.
The inability to produce speech sounds at normal volume.
A term referring to the presence of tumor emboli or tumor masses within any circulatory vessel.
The reemergence of a neoplasm after a period of remission.
Compression-induced traumatic break, and resulting collapse, of a short bone.
A pathologic bone fracture due to osteoporosis. It is generally caused by a fall from a standing height or lower and usually involves the spine, hip, or wrist.
A general term that refers to non-neoplastic and neoplastic disorders characterized by the presence of granulomas in various anatomic sites.
A term that has been used to describe abnormal cells that come from glands in the walls of the cervix (the lower, narrow end of the uterus). These abnormal cells are found in a small number of Pap smears (a procedure used to detect cervical cancer) and may be a sign of more serious lesions or cancer. The term used now is atypical glandular cells.
A rash associated with systemic lupus erythematosus.
Recurrent ulceration and fat necrosis, associated with loss of subcutaneous tissue and a decrease in lower leg circumference
A chest X-ray finding indicating the presence of a radio-opaque area in the lung. The opacification is caused by fluid or solid material within the airways or lung parenchyma.
A decrease in the strength of the diaphragm.
A bulging of the interatrial septum towards one side. In adults, atrial septal aneurysm can be defined as a protrusion of the aneurysm of >10 mm beyond the plane of the atrial septum as measured by transesophageal echocardiography.
Infarctions that occur in the BRAIN STEM which is comprised of the MIDBRAIN; PONS; and MEDULLA OBLONGATA. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury.
A congenital abnormality in the sacral region of the spine in which the meninges protrude through a defect in the spinal column.
An abnormal connection between arteries and veins, occurring within the retinal vasculature, which can result in visual changes, and blindness.
A congenital abnormality in which a part of the upper or lower eyelid tissue is missing.
An eyelash that emerges from the underside (conjunctiva) of the upper or lower eyelid.
Inflammation of the mucous membranes lining the gastrointestinal tract.
A narrowing or stricture within the digestive system.
Bleeding originating from the jejunal wall.
Bleeding originating from the ileal wall.
Disorder characterized by a wide range of structural changes in PERITONEUM, resulting from fibrogenic or inflammatory processes. Peritoneal fibrosis is a common complication in patients receiving PERITONEAL DIALYSIS and contributes to its gradual decrease in efficiency.
A variant of acute cholecystitis with inflammation of the GALLBLADDER that is characterized by the pockets of gas in the gallbladder wall. It is due to secondary infection caused by gas-forming organisms, and has a high risk of perforation.
Obstruction of the pancreatic duct leading to swelling of the pancreas as a whole
A drug-induced photodermatosis characterized by skin fragility, erythema, and the appearance of tense bullae, erosions and scarring in the absence of abnormalities in porphyrin metabolism.
Narrowing of the luminal diameter of one or both ureters due to intrinsic factors.
A usually congenital abnormality characterized by the partial obstruction of the junction between the renal pelvis and ureter. It may lead to hydronephrosis.
Dilatation of the ureter caused by obstruction of urine flow.
A single cyst in the kidney with several compartments.
A syndrome characterized by abnormal secretion of renin in conjunction with neoplastic growth occurring anywhere in the body.
A collection of pus within a testicle. Ultrasonographic features include shaggy, irregular walls, intratesticular location, low-level internal echoes, and occasionally, hypervascular margins.
Apnea occurring during the neonatal period.
Severe head pain with sudden onset, reaching its maximum intensity in less than one minute and lasting from one hour to ten days.
Atrophy of the choroid and retinal layers of the fundus.
Well-demarcated area(s) of partial or complete depigmentation in the fundus, reflecting atrophy of the retinal pigment epithelium with associated retinal photoreceptor loss.
Partial or complete opacity of the crystalline lens of both eyes that decreases visual acuity and eventually results in blindness. Some cataracts appear in infancy or in childhood, but most develop in older individuals. (Sternberg Diagnostic Surgical Pathology, 3rd ed.)
An inward turning (inversion) of the margin of the upper eyelid. [ORCID:0000-0003-0986-4123]
The presence of small, white vitreous opacities consisting of calcium phosphate and complex, layered lipid deposits.
Partial or complete hearing loss in one ear.
Partial or complete loss of the ability to detect or understand sounds present in an infant within its first month after birth.
A syndrome characterized by abnormal secretion of growth hormone in conjunction with neoplastic growth occurring anywhere in the body.
A syndrome characterized by abnormal secretion of prolactin in conjunction with neoplastic growth occurring anywhere in the body.
A syndrome characterized by abnormal secretion of aldosterone in conjunction with neoplastic growth occurring anywhere in the body.
A syndrome characterized by abnormal secretion of calcitonin in conjunction with neoplastic growth occurring anywhere in the body.
A form of cyanosis that occurs when there is a decrease in oxygen saturation in the arterial blood, usually with an SaO2 of below 75%
Absence of transferrin, a protein that transports iron, in the blood.
bacterial, viral, or parasitic diseases transmitted to humans and animals by infected arthropods, including ticks.
Child or adult deprived of minimally accepted standards of food, shelter, clothing, or care.
The benzathine salt form of cephapirin, a semisynthetic, broad-spectrum, first-generation cephalosporin with antibacterial activity. Cephapirin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
A sodium salt form of sulfabromomethazine, a long-acting derivative of sulfamezathine that is used in the poultry, swine and cattle industries for the treatment of coccidiosis and various bacterial infections.
The hydrochloride salt form of pirlimycin, a derivative of clindamycin with a 6-membered ring replacing clindamycin's 5-membered ring. Compared to clindimycin, pirlimycin has increased activity against gram-positive bacteria, including Staphylococcus aureus and coagulase negative species of Staphylococcus and Streptococcus. This agent is primarily used in the treatment of mastitis in cattle.
The hydrobromide salt of halofuginone, a semisynthetic quinazolinone alkaloid anticoccidial derived from the plant Dichroa febrifuga, with antifibrotic and potential antineoplastic activities. Halofuginone specifically inhibits collagen type I gene expression and matrix metalloproteinase 2 (MMP-2) gene expression, which may result in the suppression of angiogenesis, tumor stromal cell development, and tumor cell growth. These effects appear to be due to halofuginone-mediated inhibition of the collagen type I and MMP-2 promoters. Collagen type I and MMP-2 play important roles in fibro-proliferative diseases.
A class of agents that act by selectively inhibiting angiotensin II receptor activation in the renin-angiotensin-aldosterone system. Angiotensin II receptor antagonists bind to and block the activation of angiotensin II type 1 (AT1) receptors, thereby reducing production and secretion of aldosterone, amongst other actions. The combined effects result in reduction of blood pressure. Although this class of agents is also used in diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure, it is primarily used for the treatment of hypertension in cases where the patient is intolerant of ACE inhibitor therapy.
A health condition or medical problem that was diagnosed or treated before a specific date.
An abnormal accumulation of fluid beneath the skin of the arms.
An abnormal color of the urine, that is, the color of the urine appears different from the usual straw-yellow color.
Co-existence of an intrauterine pregnancy with an intrauterine device.
An act by a minor that is punishable by law.
Vague, uneasy feeling of discomfort or dread generated by perceptions of a real or imagined threat to one's existence.
An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex.
An abnormality of the auditory evoked potentials, which are used to trace the signal generated by a sound, from the cochlear nerve, through the lateral lemniscus, to the medial geniculate nucleus, and to the cortex.
A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)
Painful sensation in the face, between the eyes, or upper teeth originating from the sinuses. It is usually caused by sinus infections.
A broad classification of disorders where circulating numbers of B lymphocytes are decreased or ineffective. Complement components and the production of antibodies may also be deficient.
A cytotoxic primary cutaneous T-cell lymphoma. Recent studies suggest there are at least two groups of subcutaneous panniculitis-like T-cell lymphomas, each with distinct histologic features, immunophenotypic profile, and prognosis. One group has an alpha/beta, CD8 positive phenotype, involves only subcutaneous tissues, and usually has an indolent clinical course. The second group has a gamma/delta phenotype, is CD8 negative, often co-expresses CD56, is not confined to the subcutaneous tissues, and usually has a poor prognosis. In the recent WHO-EORTC classification, the term subcutaneous panniculitis-like T-cell lymphoma is reserved for cases with an alpha/beta, CD8 positive phenotype. Cases with a gamma/delta phenotype are included in the group of cutaneous gamma/delta T-cell lymphomas.
An acute myeloid leukemia with monocytic and granulocytic differentiation and the presence of a characteristically abnormal eosinophil component in the bone marrow. This type of acute myeloid leukemia has a favorable prognosis. (WHO, 2001)
An acute myeloid leukemia (AML) in which the blasts do not show evidence of myeloid differentiation by morphology and conventional cytochemistry. (WHO, 2001)
Substances that can function like HEMOGLOBINS in the capacity to carry oxygen to and carbon dioxide away from the tissues when introduced into the blood stream. The best known are the perfluorocarbon emulsions.
A form of cataract in which the lens substance has shrunk, leaving a collapsed, flattened capsule with little or no cortex or epithelium on the lens.
A category of developmental disorders characterized by impaired communication and socialization skills. The impairments are incongruent with the individual's developmental level or mental age. These disorders can be associated with general medical or genetic conditions.
A benign or malignant neoplasm that affects the placenta. Representative examples include hemangioma and choriocarcinoma.
Mulibrey nanism is a rare autosomal recessive growth disorder with prenatal onset, including occasional progressive cardiomyopathy, characteristic facial features, failure of sexual maturation, insulin resistance with type 2 diabetes, and an increased risk for Wilms tumor (summary by Hamalainen et al., 2006).
A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state.
A protein extract of human menopausal urine in which LUTEINIZING HORMONE has been partially or completely removed. Urofollitropin represents FOLLICLE STIMULATING HORMONE from the urine.
The sodium salt of a semisynthetic heparin-like glucosaminoglycan. Although its mechanism of action is unknown, pentosan polysulfate may act as a buffer to control cell permeability by preventing irritating solutes from reaching cells coated with it. Administered orally, excreted pentosan polysulfate adheres to the urinary bladder wall, preventing irritants from entering bladder cells and the development or progression of interstitial cystitis (IC), a complication of some chemotherapies. This agent also exhibits anticoagulant and fibrinolytic properties.
The magnesium salt of valproic acid (2-propylpentanoic acid) with antiepileptic and potential antineoplastic activities. Magnesium valproate dissociates in the gastrointestinal tract and is absorbed into the circulation as magnesium ions and valproic acid ions; valproic acid may inhibit histone deacetylases, inducing tumor cell differentiation, apoptosis, and growth arrest. In addition, valproic acid exerts an antiepileptic effect, likely by inhibiting enzymes that catabolize the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) catabolism and so increasing concentrations of GABA in the central nervous system (CNS). The presence of the magnesium in this agent may contribute to its anticonvulsant activity and sedative properties.
A direct metabolite of dehydroepiandrosterone (DHEA) and a precursor for testosterone with immunostimulatory activity and minimal androgenic activity. Androstenediol stimulates the differentiation of hematopoietic precursor cells into leukocytes and platelets, which can counteract the immunotoxicity of radiation exposure.
A complication after CHOLEDOCHODUODENOSTOMY when food, stones, or other debris accumulate in the common bile duct.
A lung with reduced markings on its chest radiograph and increased areas of transradiancy (hyperlucency). A hyperlucent lung is usually associated with pulmonary emphysema or PNEUMOTHORAX.
A benign or malignant neoplasm affecting the retina. Representative examples of benign neoplasms include retinocytoma and hemangioma. Representative examples of malignant neoplasms include retinoblastoma, lymphoma and melanoma.
Benign and malignant neoplasms which arise from or metastasize to the optic or second cranial nerve which extends from the optic disc of the eye and joins the optic chiasm. Clinical features may include visual loss, proptosis, and local pain. The majority of optic nerve tumors or optic gliomas.
Reduction of CEREBROSPINAL FLUID pressure characterized clinically by ORTHOSTATIC HEADACHE and occasionally by an ABDUCENS NERVE PALSY; HEARING LOSS; NAUSEA; neck stiffness, and other symptoms. This condition may be spontaneous or secondary to CEREBROSPINAL FLUID LEAK; SPINAL PUNCTURE; NEUROSURGICAL PROCEDURES; DEHYDRATION; UREMIA; trauma (see also CRANIOCEREBRAL TRAUMA); and other processes. Chronic hypotension may be associated with subdural hematomas (see HEMATOMA, SUBDURAL) or hygromas. (From Semin Neurol 1996 Mar;16(1):5-10; Adams et al., Principles of Neurology, 6th ed, pp637-8)
Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
A pharmacological agent that kills cells in the bone marrow.
An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.
INFLAMMATION of the LIVER in humans caused by HEPATITIS B VIRUS lasting six months or more. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.
INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.
INFLAMMATION of the LIVER in humans caused by HEPATITIS DELTA VIRUS in conjunction with HEPATITIS B VIRUS and lasting six months or more.
Congenital structural deformities, malformations, or other abnormalities of the maxilla and face or facial bones.
An I 131 radioiodinated synthetic analogue of the neurotransmitter norepinephrine. Iobenguane localizes to adrenergic tissue and, in radioiodinated forms, may be used to image or eradicate tumor cells that take up and metabolize norepinephrine.
An extremely rare condition manifested as monoclonal IMMUNOGLOBULIN M dysproteinemia without features of lymphoproliferative disease, but with chronic urticaria, fever of unknown origin, disabling bone pain, hyperostosis, and increased erythrocyte sedimentation rate.
A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.
Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information.
Mental disorders related to feeding and eating usually diagnosed in infancy or early childhood.
Markedly disturbed and developmentally inappropriate social relatedness that begins before age 5 and is associated with grossly pathological child care. The child may persistently fail to initiate and respond to social interactions in a developmentally appropriate way (inhibited type) or there may be a pattern of diffuse attachments with nondiscriminate sociability (disinhibited type). (From DSM-V)
A category of psychiatric disorders which have as their most predominant feature a disturbance in mood.
Marked disorders of thought (delusions, hallucinations, or other thought disorder accompanied by disordered affect or behavior), and deterioration from a previous level of functioning. Individuals have one o more of the following symptoms: delusions, hallucinations, and disorganized speech. (from DSM-5)
Mental disorders related to sexual dysfunction, paraphilias, and gender identity disorders.
A proprietary adjuvant, applicable for water-in-oil (W/O; 30/70 v/v) vaccine emulsion, with potential immunoadjuvant activity. Montanide ISA 720 is made of natural metabolizable non-mineral oil and a highly refined emulsifier from the mannide mono-oleate family; it is rapidly metabolized and eliminated, and may be used in various vaccines, including cancer vaccines. Upon administration, Montanide ISA 720 forms a depot at the injection site and is therefore capable of slowly releasing the antigen(s) from the injection site. This may result in enhanced cellular and humoral immune responses to the antigen vaccine.
A bifunctional mechlorethamine derivative with alkylating and antimetabolite activities. Although the exact mechanism of action of bendamustine is unknown, this agent appears to alkylate and crosslink macromolecules, resulting in DNA, RNA and protein synthesis inhibition, and eventually the induction of apoptosis.
An imidazole derivative and a selective alpha-2 adrenergic receptor agonist. Upon ocular administration, brimonidine acts on the blood vessels causing them to constrict which leads to a decrease in the production of aqueous humor. Brimonidine also enhances the uveoscleral outflow of aqueous humor. This reduces intraocular pressure.
An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.
A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.
The nitrate salt form of omoconazole, a topical imidazole derivative with antifungal activity against Candida albicans, Malassezia furfur and dematophytes.
A synthetic indolocarbazole multikinase inhibitor with potential antiangiogenic and antineoplastic activities. Midostaurin inhibits protein kinase C alpha (PKCalpha), vascular endothelial growth factor receptor 2 (VEGFR2), c-kit, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) tyrosine kinases, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors.
A synthetic, terpene-based cannabinoid derivative devoid of cannabinoid receptors 1 and 2 agonist activity and with potential neuroprotective, antiinflammatory and antineoplastic activities. Functioning as an N-Methyl-D-aspartate (NMDA) receptor antagonist, dexanabinol protects neuronal cells against NMDA and glutamate neurotoxicity. This agent also scavenges peroxy radicals and protects neurons from the damages of reactive oxygen species. Furthermore, dexanabinol inhibits the activity of nuclear factor kappa B (NF-kB), thereby preventing the expression of NF-kB target genes, such as tumor necrosis factor alpha, cytokines and inducible nitric oxide synthase. As a result, this agent may restore apoptotic processes in cancerous cells. NF-kB is activated in a variety of cancer cells and plays a key role in the regulation of apoptosis and cellular proliferation.
The hydrochloride salt of ramosetron, a selective serotonin (5-HT) receptor antagonist with potential antiemetic activity. Upon administration, ramosetron selectively binds to and blocks the activity of 5-HT subtype 3 (5-HT3) receptors located in the vagus nerve terminal and in the vomiting center in the central nervous system (CNS), suppressing chemotherapy-induced nausea and vomiting.
A docosanoid and a structural analogue of an inactive biosynthetic cyclic derivative of arachidonic acid, 13,14-dihydro-15-keto-prostaglandin F 2a. Although the mechanism of action is unknown, unoprostone isopropyl may reduce elevated intraocular pressure by increasing the outflow of aqueous humor upon ocular administration.
A dual action selective histamine H1 receptor antagonist and mast cell stabilizer with anti-allergic activity. Olopatadine stabilizes mast cells and prevents histamine release from mast cells. In addition, this agent also blocks histamine H1 receptors, thereby preventing histamine from binding to these receptors. Both actions prevent the effects of histamine on capillaries, bronchial smooth muscle, and gastrointestinal (GI) smooth muscle, including histamine-induced vasodilation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of GI smooth muscle. This drug also prevents histamine-induced pain and itching of mucous membranes.
An indan and piperidine derivative that acts as a selective and reversible inhibitor of ACETYLCHOLINESTERASE. Donepezil is highly selective for the central nervous system and is used in the management of mild to moderate DEMENTIA in ALZHEIMER DISEASE.
A synthetic, benzimidazole-derived angiotensin II receptor antagonist prodrug with antihypertensive activity. After hydrolysis of candesartan cilexetil to candesartan during gastrointestinal absorption, candesartan selectively competes with angiotensin II for the binding of the angiotensin II receptor subtype 1 (AT1) in vascular smooth muscle, blocking angiotensin II-mediated vasoconstriction and inducing vasodilatation. In addition, antagonism of AT1 in the adrenal gland inhibits angiotensin II-stimulated aldosterone synthesis and secretion by the adrenal cortex; sodium and water excretion increase, followed by a reduction in plasma volume and blood pressure.
A synthetic lipid-lowering agent. Cerivastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent lowers plasma cholesterol and lipoprotein levels, and modulates immune responses by suppressing major histocompatibility complex II on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. Muscle toxicity (myopathy and rhabdomyolysis) precludes the clinical use of this agent.
A member of the triptan class of agents with anti-migraine properties. Zolmitriptan selectively binds to and activates serotonin (5-HT) 1B receptors expressed in intracranial arteries and 5-HT 1D receptors located on peripheral trigeminal sensory nerve terminals in the meninges and central terminals in brainstem sensory nuclei. Receptor binding results in constriction of cranial vessels, reduction of vessel pulsation and inhibition of nociceptive transmission, thereby providing relief of migraine headaches. Zolmitriptan may also relieve migraine headaches by inhibition of pro-inflammatory neuropeptide release.
A difluorocyclopropyl quinoline. Zosuquidar trihydrochloride binds with high affinity to P-glycoprotein and inhibits P-glycoprotein-mediated multidrug resistance (MDR). P-glycoprotein, encoded by the MDR-1 gene, is a member of the ATP-binding cassette superfamily of transmembrane transporters and prevents the intracellular accumulation of many natural product-derived cytotoxic agents. (NCI04)
A kappa-opioid receptor agonist with edema relieving activity. Niravoline inhibits the scretion of the antiduretic hormone vasopressin thereby causing a diuretic effect.
A member of the tyrphostin family of tyrosine kinase inhibitors, that selectively inhibits epidermal growth factor. (NCI)
A drug used to treat erectile dysfunction. Sildenafil relaxes the smooth muscle of the penis to allow increased blood flow and erection. It is a type of phosphodiesterase inhibitor.
A humanized recombinant monoclonal antibody directed against CD33, a cell surface antigen found on myeloid leukemia blasts and early hematopoietic progenitor cells. Lintuzumab stimulates antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells expressing CD33, resulting in a decrease in tumor burden. The humanized version of this monoclonal antibody exhibits less immunogenicity and improved binding affinity compared to its murine counterpart.
A non-depolarizing skeletal muscle relaxant of the benzylisoquinolinium class. Cisatracurium besylate acts as a competitive acetylcholine antagonist that binds to nicotinic receptors at the neuromuscular junction. Compared to other neuromuscular blocking agents, it is intermediate in its onset and duration of action. Cisatracurium besylate is used to maintain neuromuscular relaxation during major surgical procedures, primarily to facilitate endotracheal intubation. Cisatracurium besylate can cause bronchospasms, hypotension, and bradycardia.
Thrombospondin-2 (1172 aa, ~130 kDa) is encoded by the human THBS2 gene. This protein plays a role in both cell-cell and cell-matrix interactions.
A recombinant form of GC (group-specific component) protein-derived macrophage-activating factor (GC-MAF) with potential immunostimulating and antineoplastic activities. Upon administration, globulin component macrophage-activating factor is able to stimulate macrophages to kill cancer cells, inhibit angiogenesis and stimulate the immune system. This decreases tumor cell proliferation. GC, also known as vitamin D binding protein (VDBP), is converted to GC-MAF by enzymes located in the membrane of B- and T-lymphocytes. However, deglycosylated GC protein cannot be converted to GC-MAF. Endogenous GC-MAF is often not activated in patients with cancer due to an increased activity of nagalase (also called alpha-N-acetylgalactosaminidase), an enzyme secreted by cancer cells that mediates the deglycosylation of GC; thus preventing macrophage activation and immunosuppression.
A fluorene derivative that is used in combination with ARTEMETHER for the treatment of MALARIA (see ARTEMETHER-LUMEFANTRINE COMBINATION).
A nitric oxide (NO) donating derivative of acetylsalicylic acid with anti-inflammatory, analgesic, antipyretic, antithrombotic, gastroprotective and potential antitumor activities. The acetylsalicylic acid derivative moiety of this agent inhibits the activities of cyclooxygenase (COX) I and II, preventing the formation of prostaglandins and thromboxanes. A reduction in prostaglandin synthesis accounts for this agent's anti-inflammatory, anti-pyretic and analgesic activities; a reduction in thromboxane A2 synthesis results in an irreversible inhibition of platelet aggregation. NO donation by this agent, after cleavage from the acetylsalicylic acid derivative in vivo, may protect the gastric mucosa against the damaging effects of the aspirin derivative by modulating prostaglandins. In tumor cells, the NO donating moiety may block the cell cycle in the G1 and G2 phases and may induce apoptosis through caspase-mediated mechanisms.
A semisynthetic sesquiterpene derivative of illudin S, a natural toxin isolated from the fungus Omphalotus illudens. Irofulven alkylates DNA and protein macromolecules, forms adducts, and arrests cells in the S-phase of the cell cycle. This agent requires NADPH-dependent metabolism by alkenal/one oxidoreductase for activity. Irofulven is more active in vitro against tumor cells of epithelial origin and is more resistant to deactivation by p53 loss and MDR1 than other alkylating agents. (NCI04)
A valiolamine derivative and inhibitor of alpha-glucosidase with antihyperglycemic activity. Voglibose binds to and inhibits alpha-glucosidase, an enteric enzyme found in the brush border of the small intestines that hydrolyzes oligosaccharides and disaccharides into glucose and other monosaccharides. This prevents the breakdown of larger carbohydrates into glucose and decreases the rise in postprandial blood glucose levels.
An ureido-derivative of pyridine that induces differentiation in neoplastic cells, causing inhibition of cell proliferation. (NCI)
A synthetic cytidine nucleoside containing a covalently bound ethynyl group with potential antineoplastic and radiosensitizing activities. 3'-C-ethynylcytidine is metabolized in tumor cells to ethynylcytidine triphosphate (ECTP), which inhibits RNA synthesis by competitive inhibition of RNA polymerases I, II and III; subsequently, RNase L is activated, resulting in apoptosis. RNase L is a potent antiviral and antiproliferative endoribonuclease that cleaves singled stranded RNA, causes 28s rRNA fragmentation, and activates Janus Kinase (JAK), a mitochondrial-dependent apoptosis signaling molecule.
Cystatin-M (149 aa, ~17 kDa) is encoded by the human CST6 gene. This protein plays a role in the modulation of cathepsin B activity.
Angiostatic proteins that are formed from proteolytic cleavage of COLLAGEN TYPE XVIII.
A triazole with antifungal activity. Ravuconazole inhibits 14a demethylase, an enzyme involved in sterol synthesis, resulting in lysis of the fungal cell wall and fungal cell death. (NCI04)
A pyridine derivative with antitumor activity. Gimeracil enhances the antitumor activity of fluoropyrimidines by competitively and reversibly inhibiting the enzyme dihydropyrimidine dehydrogenase causing decreased degradation of the fluoropyrimidines.
A radioimmunoconjugate consisting of the murine IgG1 monoclonal antibody BW250/183 labeled with yttrium Y 90 with potential radioimmunotherapeutic activity. Yttrium Y 90 anti-CD66 monoclonal antibody BW 250/183 binds to a 95 kD nonspecific cross-reacting antigen (CD66b or NCA-95) on granulocytes, selectively delivering a cytotoxic dose of Y 90 beta radiation to CD66b-expressing cells. CD66b, a member of the carcinoembryonic antigen (CEA) family with an unknown function, appears early in the differentiation of granulopoietic cells and is expressed on the cell surface of almost all human granulocytes and their more mature precursors.
Combined vaccines consisting of DIPHTHERIA TOXOID; TETANUS TOXOID; and an acellular form of PERTUSSIS VACCINE. At least five different purified antigens of B. pertussis have been used in various combinations in these vaccines.
A prenylated flavonoid derived from the female flowers of the hops plant (Humulus lupulus L), with potential chemopreventive and antineoplastic activities. Upon administration, xanthohumol scavenges reactive oxygen species (ROS), thereby preventing DNA damage due to oxidative stress. In addition, xanthohumol is able to increase the expression of phase II cytoprotective enzymes, thereby inactivating carcinogens. This agent exerts anti-inflammatory activity, through the inhibition of inflammation-inducing enzymes, inhibits DNA synthesis, and induces apoptosis of susceptible cancer cells. Xanthohumol also decreases the expression of C-X-C chemokine receptor 4 (CXCR4), thereby preventing cancer cell invasion.
A purine derivative and competitive inhibitor of CYCLIN-DEPENDENT KINASES that has therapeutic potential as an antineoplastic and antiviral agent.
A mitochondrial uncoupling protein that is expressed in many tissues and exhibits the greatest expression in SKELETAL MUSCLE. It regulates mitochondrial ATP production and the generation of REACTIVE OXYGEN SPECIES.
A long-lasting, recombinant version of human insulin. It is an insulin analogue with myristic acid bound to the lysine at position B29 and a deletion of B30.
A short polypeptide with activity against human immunodeficiency virus (HIV). Enfuvirtide binds to the first heptad-repeat (HR1) in the gp41 viral envelope glycoprotein, thereby preventing conformational changes required for fusion of viral and cellular membranes and preventing the virus from entering a host cell.
A peptide analogue of human amylin with 3 proline substitutions at positions 25, 28 and 29, with antihyperglycemic activity. By mimicking amylin, pramlintide slows gastric emptying, inhibits digestive secretions (gastric acid, pancreatic enzymes, and bile), reduces glucagon secretion, and increases satiety; all of these actions are mediated mostly by glucose-sensitive areas in the brain stem. The overall result is a decrease in blood glucose levels. The use of pramlintide may cause an increased risk of insulin-induced hypoglycemia.
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin 11 (IL-11). Secreted by bone marrow stromal cells and a number of mesenchymal cells, IL-11 binds to and activates its cell-surface receptor, promoting primary and secondary immune responses, modulating antigen-specific antibody reactions, and preventing apoptotic cell death. This agent also stimulates the T-cell-dependent development of IgG-secreting B-cells in spleen cell cultures and may be an important regulator of megakaryocytopoiesis. (NCI04)
A cyclic lipopeptide echinocandin and beta-(1,3)-D-glucan synthase inhibitor that is used to treat internal or systemic MYCOSES.
An indolinone-based small molecule selective tyrosine kinase inhibitor with potential antineoplastic activity. SU5402 blocks the activities of vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor 1 (FGFR1) via competing with ATP for the specific binding site within the catalytic domain of these receptors. This agent was shown to inhibit cell growth, decrease cell viability in dose-dependent manner, and induce apoptosis.
A substance that inhibits the tyrosine kinase activity of fibroblast growth factor receptor 1, tyrosine phosphorylation of the PDGF receptor and the insulin receptor. (NCI)
A glucan that is structurally related to maltodextrin, with more than 85% of its molecules having molecular weights between 1640 and 45 000 Daltons (Da), and a weight-average molecular weight of about 20 000 Da; it is used in dialysis fluids as an alternative to glucose-based solutions, and to reduce adhesions after gynecological or abdominal surgery. It has also been used as a vehicle for drugs given via the peritoneal cavity.
A hematopoietic growth factor with activity on mature and immature hematopoietic progenitor cells.
A nonsteroidal anti-inflammatory drug (NSAID) with a diaryl-substituted pyrazole structure. Celecoxib selectively inhibits cyclo-oxygenase-2 activity (COX-2); COX-2 inhibition may result in apoptosis and a reduction in tumor angiogenesis and metastasis.
A lipid metabolism modulator which may inhibit angiogenesis, thereby possibly having antitumor activity. (NCI)
A product elaborated and marketed by the private Canadian laboratory. 714-X contains trimethylbicyclonitraminoheptane chloride, a nitrogenated camphor-derivative, and mineral salts in ethanol. It is claimed to cure cancer, multiple sclerosis, fibromyalgia, AIDS and other diseases by improving the body's immune function. Few inconclusive animal studies and no human trials were conducted with the product. There is no scientific evidence that 714-X is effective in treating any type of disease. It has not been proven to be safe or effective for any use. 714-X is banned by FDA for use in the USA. In Canada 714-X is legally available on compassionate grounds only through a licensed physician.
A chelated octreotide derivative with somatostatin activity. Edotreotide is produced by substituting tyrosine for phenylalanine at the 3 position of octreotide and chelated via dodecanetetraacetic acid (DOTA). Like octreotide, this edotreotide binds to somatostatin receptors (SSTRs), especially type 2, present on the cell membrane of many types of neuroendocrine tumors. When labeled with nuclides, edotreotide conjugates could result in tissue specific cytotoxicity.
A member of the tyrphostin family of tyrosine kinase inhibitors that selectively inhibits platelet-derived growth factor receptor protein. (NCI)
A mitochondrial uncoupling protein that is expressed in heart and skeletal muscle tissues. It functions to regulate tissue respiration, energy balance, and THERMOGENESIS. Mutations in the UCP3 gene are associated with OBESITY.
An immunotoxin consisting of an anti-CD40 antibody linked to a 40kD fragment of Pseudomonas exotoxin.
An endogenous 105-kDa plasma glycoprotein produced primarily by the LIVER and MONOCYTES. It inhibits a broad spectrum of proteases, including the COMPLEMENT C1R and the COMPLEMENT C1S proteases of the CLASSICAL COMPLEMENT PATHWAY, and the MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. C1-INH-deficient individuals suffer from HEREDITARY ANGIOEDEMA TYPES I AND II.
An angiopoietin that is closely related to ANGIOPOIETIN-1. It binds to the TIE-2 RECEPTOR without receptor stimulation and antagonizes the effect of ANGIOPOIETIN-1. However its antagonistic effect may be limited to cell receptors that occur within the vasculature. Angiopoietin-2 may therefore play a role in down-regulation of BLOOD VESSEL branching and sprouting.
A dipivoxil formulation of adefovir, a nucleoside reverse transcriptase inhibitor analog of adenosine with activity against hepatitis B virus (HBV), herpes virus, and human immunodeficiency virus (HIV).
A penem with a tetrahydrofuran substituent at position C2, with broad-spectrum antibacterial activity against many gram-positive and gram-negative aerobes and anaerobes. Compared with imipenem, faropenem has improved chemical stability and reduced central nervous system effects. In addition, faropenem is resistant to hydrolysis by many beta-lactamases.
A hydrochloride salt form of colesevelam, a non-absorbed polymer that binds bile acids in the intestine and lowers serum lipids.
A non-absorbed polymer that binds bile acids in the intestine, impedes their reabsorption and lowers serum lipids. In patients with type 2 diabetes mellitus, colesevelam also lowers blood glucose levels by an unknown mechanism.
A derivative of sirolimus and an inhibitor of TOR SERINE-THREONINE KINASES. It is used to prevent GRAFT REJECTION in heart and kidney transplant patients by blocking cell proliferation signals. It is also an ANTINEOPLASTIC AGENT.
A radiation-protective agent that can inhibit DNA damage by binding to the DNA. It also increases the susceptibility of blood cells to complement-mediated lysis.
An injury that results in paralysis of the muscles of the shoulder, arm, and hand. It manifests as lack of mobility in the arm. In the majority of cases there is spontaneous recovery.
Heterocyclic compounds with SULFUR and NITROGEN in the ring. This term commonly refers to the BENZOTHIADIAZINES that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
An abnormality in the rate and degree to which platelets aggregate after the addition of an agonist that stimulates platelet clumping. Platelet aggregation is measured using aggregometer to measure the optical density of platelet-rich plasma, whereby platelet aggregation causes the plasma to become more transparent.
An electrocardiographic finding in which a failure of impulse formation or conduction in the sinus node produces prolongation of the P-P interval or dropped P waves. The threshold for the prolongation of the P-P interval is not well defined. (CDISC)
The presence of skeletal muscular atrophy (which is also known as amyotrophy). [HPO:probinson]
A finding of significant hearing loss documented with audiometric testing.
A type of insomnia characterized by waking up (too) early in the morning. []
A type of urinary cast composed of cells incorporated in a protein matrx. The cells can be those found in the urinary sediment (erythrocytes, leuklocytes, renal tubular epithelial cells).
A carcinoma that arises from the duodenum. The vast majority of cases are adenocarcinomas.
A general term that refers to hyperplastic proliferations of the epithelial cells in the breast parenchyma. Examples include atypical ductal hyperplasia, usual ductal hyperplasia, columnar cell hyperplasia, and atypical lobular hyperplasia.
Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.
An decrease in the level of triglycerides in the blood.
A non-congenital, benign vascular lesion with a central punctum (arteriole) that is surrounded by thin-walled capillaries in a radial pattern. It occurs as the result of the dilatation of pre-existing vessels and is most often an incidental finding. The lesion may also be found in association with hypermetabolic states or chronic disease.
A type of telangiectasia, comprised of a central red spot with radiating, red extensions, that is present at the time of birth.
A level of sedation that is greater than the intended level.
A painful sensation in the distal thigh area.
Paralysis of the recurrent laryngeal nerve. Causes include surgical and non-surgical traumas, neoplasms (e.g., lung carcinoma), and inflammatory neuritis.
A rupture in the jejunal wall due to traumatic or pathologic processes.
Thrombophlebitis in the veins surrounding an injection site.
The condition resulting from the spread of bacterial products (toxins) by the bloodstream.
A morphological abnormality of the vestibule, the central part of the osseous labyrinth that is situated medial to the tympanic cavity, behind the cochlea, and in front of the semicircular canals.
Studies to identify or characterize the mechanism of action of non-infectious exogenous agents, conditions, or procedures that initiate, promote, or otherwise contribute to the development of cancer. Although infectious agents are excluded from this definition, extrinsic factors that increase exposure to these agents (e.g., occupation, sexual activity, needle sharing, transfusion) are considered environmental.
A small elevation of the skin containing cloudy or purulent material usually consisting of necrotic inflammatory cells.
Narrowing or stricture of the bladder neck.
Hypochondrogenesis is a rare, severe disorder of bone growth. This condition is characterized by a small body, short limbs, and abnormal bone formation (ossification) in the spine and pelvis.Affected infants have short arms and legs, a small chest with short ribs, and underdeveloped lungs. Bones in the skull develop normally, but the bones of the spine (vertebrae) and pelvis do not harden (ossify) properly. The face appears flat and oval-shaped, with widely spaced eyes, a small chin, and, in some cases, an opening in the roof of the mouth called a cleft palate. Individuals with hypochondrogenesis have an enlarged abdomen and may have a condition called hydrops fetalis in which excess fluid builds up in the body before birth.As a result of these serious health problems, some affected fetuses do not survive to term. Infants born with hypochondrogenesis usually die at birth or shortly thereafter from respiratory failure. Babies who live past the newborn period are usually reclassified as having spondyloepiphyseal dysplasia congenita, a related but milder disorder that similarly affects bone development.
An abnormal bluish coloration of the sclera.
An abnormal increase in the size of the kidney.
A congenital abnormality characterized by the absence of one or both kidneys.
A meningioma that affects the cerebral hemispheres.
Swelling due to an excessive accumulation of fluid in facial tissues.
A pathologic condition that results from a disease, treatment, or injury.
The hydrochloride salt form of acebutolol, a synthetic butyranilide derivative with hypotensive and antiarrhythmic activity. Acebutolol acts as a cardioselective beta-adrenergic antagonist with little effect on bronchial receptors and has intrinsic sympathomimetic properties. Having stabilizing and quinidine-like effects on cardiac rhythm, Acebutolol is used in ventricular arrhythmias. Other indications include hypertension, alone or in combinations with other agents. (NCI04)
A synthetic quinolinone derivative, antihypertensive Carteolol Hydrochloride is a nonselective beta-adrenoceptor blocking agent for beta-1 and beta-2 receptors with no membrane-stabilizing activity but moderate intrinsic sympathomimetic effects. It is used for treatment of hypertension and certain arrhythmias, and as an anti-angina and antiglaucoma agent. (NCI04)
A substance being studied in the treatment of some types of cancer and other conditions. When used together with interleukin-2, histamine dihydrochloride may help some immune cells find and kill tumor cells. It is a type of biological response modifier.
The hydrochloride salt form of mexiletine, a local anesthetic and antiarrhythmic (Class IB) agent structurally related to lidocaine. Mexiletine exerts its antiarrhythmic effect by inhibiting the inward sodium current in cardiac cells, thereby reducing the rate of rise of the cardiac action potential (phase 0) and decreases automaticity in the Purkinje fibers. This slows nerve impulses in the heart and stabilizes the heartbeat. Mexiletine's anesthetic activity is due to its ability to block sodium influx in peripheral nerves, thereby reducing the rate and intensity of pain impulses reaching the central nervous system.
The potassium salt form of aminobenzoate, with anti-inflammatory and antifibrotic activities. Aminobenzoate potassium increases oxygen uptake at the tissue level and may enhance monoamine oxidase (MAO) activity, which requires oxygen as a substrate. Enhanced MAO activity maybe accountable for the prevention or regression of fibrosis, which may occur due to too much serotonin or too little MAO activity.
The hydrochloride salt form of betaxolol, a beta-1-selective adrenergic receptor antagonist without intrinsic sympathomimetic activity. Betaxolol hydrochloride acts on the heart and circulatory system and decreases cardiac contractility and rate, thereby reducing cardiac output. When applied topically in the eye, it lowers intraocular pressure by reducing aqueous humor secretion.
The fumarate salt of a synthetic phenoxy-2-propanol-derived cardioselective beta-1 adrenergic receptor antagonist with antihypertensive and potential cardioprotective activities. Devoid of intrinsic sympathomimetic activity, bisoprolol selectively and competitively binds to and blocks beta-1 adrenergic receptors in the heart, decreasing cardiac contractility and rate, reducing cardiac output, and lowering blood pressure. In addition, this agent may exhibit antihypertensive activity through the inhibition of renin secretion by juxtaglomerular epithelioid (JGE) cells in the kidney, thus inhibiting activation of the renin-angiotensin system (RAS). Bisoprolol has been shown to be cardioprotective in animal models.
The hydrochloride salt of an indazole derivative with antiemetic properties. As a selective serotonin receptor antagonist, granisetron competitively blocks the action of serotonin at 5-hydroxytryptamine3 (5-HT3) receptors, resulting in the suppression of chemotherapy- and radiotherapy-induced nausea and vomiting.
Tumor cells that remain in the body following cancer treatment.
A mesylate salt form of delavirdine, a synthetic, non-nucleoside reverse transcriptase inhibitor. In combination with other anti-retroviral drugs, this agent has been shown to reduce HIV viral load and increase CD4 leukocyte counts in patients. As an inhibitor of the cytochrome P450 system, delavirdine may result in increased serum levels of co-administered protease inhibitors metabolized by the cytochrome P450 system.
The sulfate salt of the short-acting sympathomimetic agent albuterol, a 1:1 racemic mixture of (R)-albuterol and (S)-albuterol with bronchodilator activity. Albuterol stimulates beta2-adrenergic receptors in the lungs, thereby activating the enzyme adenylate cyclase that catalyzes the conversion of ATP to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP concentrations relax bronchial smooth muscle, relieve bronchospasms, and reduce inflammatory cell mediator release, especially from mast cells. To a lesser extent albuterol stimulates beta1-adrenergic receptors, thereby increasing the force and rate of myocardial contraction.
Hyperlysinemia type I is an autosomal recessive metabolic condition with variable clinical features. Some patients who present in infancy with nonspecific seizures, hypotonia, or mildly delayed psychomotor development have been found to have increased serum lysine and pipecolic acid on laboratory analysis. However, about 50% of probands are reported to be asymptomatic, and hyperlysinemia is generally considered to be a benign metabolic variant (summary by Tondo et al., 2013; Houten et al., 2013). The AASS gene encodes a bifunctional enzyme: lysine alpha-ketoglutarate reductase and saccharopine dehydrogenase. In hyperlysinemia type I, both enzymatic functions of AASS are defective; in hyperlysinemia type II, also known as saccharopinuria (268700), some of the first enzymatic function is retained (Cox, 1985; Cox et al., 1985).
The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria (IG; 242600), a benign inborn error of amino acid transport, is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG) (summary by Broer et al., 2008). A phenotype of combined glucosuria and glycinuria has been described (see 138070).
A condition characterized by a decrease in the number of neutrophils in the blood below established reference ranges in a newborn.
Amyotrophic lateral sclerosis-parkinsonism/dementia complex of Guam is a neurodegenerative disorder with unusually high incidence among the Chamorro people of Guam. Both ALS and parkinsonism-dementia are chronic, progressive, and uniformly fatal disorders in this population. Both diseases are known to occur in the same kindred, the same sibship, and even the same individual.
Congenital oculomotor apraxia, first reported by Cogan (1952), is characterized by (1) defective or absent horizontal voluntary eye movements, and (2) defective or absent horizontal ocular attraction movements. Oculomotor apraxia occurs in ataxia-telangiectasia (208900). Also see ataxia-oculomotor apraxia syndrome (208920; 606002). Oculomotor apraxia has been observed in the neuronopathic form of Gaucher disease (type III; 231000) (Erikson and Wahlberg, 1985; Gross-Tsur et al., 1989).
Retinal phenotype characterised by cone photoreceptor dysfunction and preserved rod system. The abnormality is typically stationary or very slowly progressive and findings may include reduced central vision, colour vision abnormalities, nystagmus and photophobia.
A rare disorder of the eye in which the endothelium lining the interior of the cornea proliferates causing unusually high pressure in the eye, distortion of the iris and corneal edema.
An abatement in intensity or degree (as in the manifestations of a disease).
Shock resulting from neurogenic vasodilation, which can be produced by cerebral trauma or hemorrhage, spinal cord injury, deep general or spinal anesthesia, or toxic central nervous system depression.
An aperture or hollow space within a solid mass
A bending or abnormal curvature affecting a long bone of the leg.
A rapidly growing, poorly circumscribed, mass-forming proliferation that arises from the skeletal muscle. It is characterized by the presence of spindle-shaped fibroblasts, round ganglion-like cells, myxoid to collagenous stroma formation, and high mitotic activity. It recurs only rarely following local excision and does not metastasize.
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Nodular localized form of amyloidosis with predominantly thoracic localization (pulmonary amyloidosis), considered as secondary protein structure disease in which insoluble protein fibrils accumulate extracellularly. The form of primary amyloid in amyloidoma is characterized by abnormal deposition of light chain proteins composed of monoclonal immunoglobulin. Pulmonary amyloidomas are rare and are often found incidentally as solitary or multiple calcified nodules and masses on chest radiographs in asymptomatic elderly patients. Cavitation is rare, the prognosis is good.
A white appearance of the nails can result from whitening of the nail plate (true leukonychia), the nail bed (pseudoleukonychia), or neither (apparent leukonychia), and can be due to a variety of factors including infectious, metabolic, or systemic diseases, trauma, or drugs. One of the rare causes of whitening of the nail plate is hereditary leukonychia (summary by Kiuru et al., 2011). Leukonychia may involve all of the nail (leukonychia totalis) or only part of the nail (leukonychia partialis), or can appear as one or more transverse bands (leukonychia striata) or white spots (leukonychia punctata). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
A digit with two nails, with at least some soft tissue between them.
Neurocutaneous melanosis, or neuromelanosis, is characterized by the presence of melanin-producing cells within the brain parenchyma or leptomeninges, which may lead to clinically apparent neurologic signs and symptoms, such as seizures. Other neurologic abnormalities, including hydrocephalus, arachnoid cysts, tumors, and syringomyelia, may also occur. The disorder is a rare but severe manifestation of congenital melanocytic nevus syndrome (CMNS; 137550). Some patients with neurocutaneous melanosis or CMNS may develop malignant melanoma. The incidence of neurologic involvement, development of malignant melanoma, and death is significantly associated with the projected adult size of the largest congenital melanocytic nevus, particularly those greater than 40 cm (summary by Kinsler et al., 2008; Kinsler et al., 2013).
A mutation that converts a sense codon (CODON) into a stop codon (CODON, TERMINATOR) or an unassigned codon and leads to the formation of truncated proteins.
A mode of inheritance in which a trait or disorder results from a de novo mutation occurring after conception, rather than being inherited from a preceding generation.
Any cytoskeletal process involving microtubule structures and their associated proteins.
Cell Membrane Alteration consists of a change in the quality of the existing state of activities involved in the composition, fabrication, construction, or maintenance of the regular structure and function of semipermeable lipid bilayer membranes that surround or reside within a cell.
The lysosomal-vacuolar pathway has a role in the controlled intracellular digestion of macromolecules such as protein complexes and organelles. This feature refers to the presence of an abnormally increased number of autophagic vacuoles in muscle tissue.
Increased numbers of mesangial cells per glomerulus, defined as four or more nuclei in a peripheral mesangial segment.
A developmental disorder characterized by keratotic papules of skin of hands and soles with disorganization of dermal elastic fibers that does not appear to be due to trauma or sunlight
An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
A melanocytic neoplasm displaying morphologic features that are intermediate between those of benign nevus and melanoma. It is characterized by a nodular architectural growth resembling a melanoma, and a loss of nevus cell maturation. The melanocytic cells forming the nodular growth are uniform, and they may display a high mitotic rate, but they do not show cytologic atypia.
A liposarcoma characterized by the presence of round non-lipogenic primitive mesenchymal cells and small signet ring lipoblasts within a myxoid stoma with a branching vascular pattern. This category includes hypercellular lesions with round cell morphology, formerly known as round cell liposarcoma.
Coexistence of Hodgkin and non-Hodgkin lymphoma in the same anatomic site.
The presence of more than the normal number of metacarpal bones.
Adult-onset nemaline myopathy is a rapidly progressive type of nemaline myopathy (NM; see this term) characterized by a very late onset.
Childhood onset nemaline myopathy, or mild nemaline myopathy is a type of nemaline myopathy (NM; see this terms) characterized by distal muscle weakness, and sometimes slowness of muscle contraction.
A surgically created external opening into the renal pelvis.
A surgically created external opening into the trachea.
Congenital fiber-type disproportion (CFTD) myopathy is a genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions. Clarke and North (2003) stated that the diagnosis of 'congenital fiber-type disproportion' as a disease entity is one of exclusion. They also suggested that the nonspecific histologic findings should be termed 'fiber size disproportion,' thus reserving the term CFTD for those cases in which no secondary cause can be found.
Displacement of the great toe (HALLUX) towards the midline or away from the other TOES. It can be congenital or acquired.
A very rare congenital malformation characterised by a muscular appendix emerging from the left ventricular apex, rarely from the right ventricle or from both chambers, with clinical manifestations ranging from asymptomatic to life-threatening haemodynamic collapse. Often associated with other cardiac abnormalities but is mostly an isolated anomaly. It is mostly found in infants and children and occasionally as an incidental finding in adults. Two types are described: fibrous and muscular. The aetiology of congenital cardiac diverticulum is not known. Haemodynamic factors may play a role.
Inflammation of the glomeruli with infiltration by polymorphonuclear leukocytes.
A type of hepatic necrosis that is concentrated around the necrosis of hepatocytes localized around the intrahepatic branch of portal vein.
Primary localized cutaneous nodular amyloidosis (PLCNA) is the most rare form of primary cutaneous amyloidosis (see this term), a skin disease characterized by the accumulation of amyloid deposits in the dermis, characterized clinically by yellowish waxy crusted nodules and papules on the face, lower extremities, trunk, scalp, and genitalia and histologically by the localized deposition of immunoglobulin-derived amyloid in the papillary dermis and subcutis. PLCNA can be associated with connective tissue disorders such as Sjögren?s syndrome and CREST syndrome (see these terms).
An increased number of local terminal placental villous capillary cross-sections, generally with decreased capillary caliber, that shows variable distribution of villi.
A rare inherited skin cancer syndrome with the coexistence of features characteristic of both multiple keratoacanthoma, Ferguson Smith type and generalised eruptive keratoacanthoma, such as multiple small miliary-type lesions, larger self-healing lesions, and nodulo-ulcerative lesions. Lesions do not have a predilection for the mucosal surfaces. Transmission is autosomal dominant.
An increase in the amount of intravascular fluid, particularly in the volume of the circulating blood.
Esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), is one of the most common cancers worldwide. Both environmental and genetic risk factors play a role in the pathogenesis of the disorder. In Europe and North America, heavy smoking, alcohol consumption, and increased body mass index (BMI) are the main environmental risk factors. In contrast, the particularly high incidence of ESCC in some areas of China, central Asia, and southern Africa is associated with nutritional deficiencies, high intake of nitrosamine-rich or pickled vegetables, and low socioeconomic status; smoking, alcohol consumption, and BMI play a lesser role in these populations. There is a tendency for familial aggregation of ESCC in high-risk geographic areas, suggesting a genetic component to increased susceptibility. Gastric cardia adenocarcinoma is another common type of cancer in China that shows similarities to ESCC in terms of geographic distribution and environmental risk factors (summary by Wang et al., 2010 and Abnet et al., 2010). Genetic Heterogeneity of Susceptibility to Esophageal Cancer See a variant in the ADH1B gene (103720.0001) for discussion of a possible genetic association with protection against squamous cell aerodigestive tract cancer, including esophageal cancer, in alcohol drinkers. See a variant in the ALDH2 gene (100650.0001) for discussion of a possible genetic association with increased risk for esophageal cancer in alcohol drinkers due to interaction between variants in the ADH1B and ALDH2 genes. See the S100A14 gene (607986) on chromosome 1q21 for a discussion of a possible association between variation in that gene and susceptibility to esophageal squamous cell carcinoma among smokers. Genetic Heterogeneity of Somatic Mutations in Esophageal Cancer Somatic mutations in several different genes have been found in esophageal cancer tissue. These genes include TP53 (191170), CDKN2A (600160), DEC1 (604767), DCC (120470), DLEC1 (604050), TGFBR2 (190182), LZTS1 (606551), RNF6 (604242), WWOX (605131), APC (611731), and RUNX3 (600210).
The hydrochloride salt of amiloride, a synthetic pyrazine derivative with antikaliuretic and diuretic properties. Amiloride inhibits sodium channels located in the distal tubules and collecting ducts of the kidney, thereby preventing the absorption of sodium and increasing its excretion along with water, to produce naturesis. In response to the hypernatremic conditions in the kidney, the plasma membrane becomes hyperpolarized and electrochemical forces are reduced, which then prevents the excretion of potassium and hydrogen into the lumen.
The hydrochloride salt form of benzphetamine, a sympathomimetic amine related to the synthetic agent amphetamine with central nervous system (CNS) stimulating and anorexic properties. Benzphetamine stimulates the release of certain catecholamines, particularly noradrenaline and dopamine, from nerve terminals in the brain and inhibits their uptake. The increase in synaptic concentrations of these catecholamines causes behavioral changes including euphoria, an increase in mental alertness and excitement, and suppresses appetite.
The mesylate salt of bromocriptine, a semisynthetic ergot alkaloid with dopaminergic, antidyskinetic, and antiprolactinemic activities. Bromocriptine selectively binds to and activates postsynaptic dopamine D2 receptors in the corpus striatum of the central nervous system (CNS). Activation of these D2 receptors activate inhibitory G-proteins, which inhibit adenylyl cyclase, preventing signal transduction mediated via cAMP and resulting in the inhibition of neurotransmission and an antidyskinetic effect. This agent also stimulates dopamine D2 receptors in the anterior pituitary gland, which results in the inhibition of prolactin secretion and lactation and may inhibit the proliferation of prolactin-dependent breast cancer cells.
The maleate salt form of brompheniramine, an alkylamine derivative and a histamine antagonist with anticholinergic and sedative properties. Brompheniramine maleate competes with histamine for the H1 receptor. This diminishes the actions of histamine on effector cells and decreases the histamine-mediated symptoms of allergic reaction such as bronchoconstriction, vasodilation, increased capillary permeability and spasmodic contractions of gastrointestinal smooth muscle.
The hydrochloride salt form of proguanil, a synthetic biguanide derivative of pyrimidine and an folate antagonist with antimalarial property. Upon hydrolysis, proguanil is converted to its active cyclic triazine metabolite, cycloguanil, by a cytochrome P450 dependent reaction. Cycloguanil selectively inhibits the bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) of plasmodium parasite, thereby disrupting deoxythymidylate synthesis and ultimately blocking DNA and protein synthesis in the parasite.
A synthetic alkylamine derivative used in allergic reactions, hay fever, rhinitis, urticaria, and asthma, antihistamine Chlorpheniramine Maleate acts as a competitive histamine H1 receptor antagonist, and displays anticholinergic and mild sedative effects as well. (NCI04)
A synthetic ethanolamine with anticholinergic, sedative, and histamine H1 antagonistic properties. Clemastine fumarate blocks the H1 histamine receptor and prevents the symptoms that are caused by histamine activity on capillaries, bronchial and gastrointestinal smooth muscles, including vasodilation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastrointestinal smooth muscles. This drug also prevents histamine-induced pain and itching of mucous membranes.
The citrate salt form of clomiphene, a triphenylethylene nonsteroidal ovulatory stimulant evaluated for antineoplastic activity against breast cancer. Clomiphene has both estrogenic and anti-estrogenic activities that compete with estrogen for binding at estrogen receptor sites in target tissues. This agent causes the release of the pituitary gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to ovulation. (NCI04)
The hydrochloride salt form of clonidine, an imidazoline derivate and centrally-acting alpha-adrenergic agonist as well as antagonist with antihypertensive activity. Clonidine hydrochloride binds to and stimulates central alpha-2 adrenergic receptors, thereby decreasing sympathetic outflow to the heart, kidneys, and peripheral vasculature. The reduction in sympathetic outflow, leads to decreased peripheral vascular resistance, decreased blood pressure, and decreased heart rate.
An imidazole derivative and broad-spectrum antimycotic agent with fungistatic properties. Econazole nitrate inhibits biosynthesis of ergosterol, thereby damaging the fungal cell wall membrane and altering its permeability which leads to a loss of essential intracellular components. In addition, econazole nitrate inhibits biosynthesis of triglycerides and phospholipids and inhibits oxidative and peroxidative enzyme activity which may contribute to cellular necrosis and cell death. Econazole nitrate is also active against some gram positive bacteria. This antifungal agent is used in the treatment various dermatomycoses.
The hydrochloride salt form of ethambutol, an ethylenediamine derivative with antibacterial activity, specifically effective against mycobacteria. Although the exact mechanism of action of ethambutol hydrochloride is unknown, ethambutol hydrochloride inhibits the transfer of mycolic acids into the cell wall of bacteria, which impedes bacterial cell growth. This agent may also interfere with RNA synthesis or inhibit other cell metabolism, thereby preventing cell multiplication and causing cell death.
The citrate salt of fentanyl, a synthetic opioid related to the phenylpiperidines with analgesic and anesthetic properties. Fentanyl exerts its analgesic effect by selectively binding to the mu-opioid receptor in the central nervous system (CNS), thereby mimicking the effects of endogenous opiates. Additional pharmacological effects of fentanyl include anxiolysis, euphoria, feelings of relaxation, respiratory depression, constipation, miosis, and cough suppression.
The hydrochloride salt form of flavoxate, a parasympatholytic agent with antispasmodic activity. Flavoxate hydrochloride competitively binds to muscarinic receptors, thereby preventing the actions of acetylcholine. This relaxes vascular smooth muscle, mainly of the urinary tract, and prevents smooth muscle contractions.
The bitartrate salt form of hydrocodone, a semisynthetic hydrogenated codeine derivative and opioid agonist with analgesic and antitussive effects. Hydrocodone primarily binds to and activates the mu-opioid receptor in the central nervous system (CNS). This leads to analgesia, euphoria, respiratory depression, miosis, decreased gastrointestinal motility, cough suppression and physical dependence. Hydrocodone is converted to hydromorphone by the cytochrome P450 enzyme CYP2D6.
The hydrochloride salt from of lidocaine, an aminoethylamide and a prototypical member of the amide class anesthetics. Lidocaine interacts with voltage-gated Na+ channels in the nerve cell membrane and blocks the transient increase in permeability of excitable membranes to Na+. This prevents the generation and conduction of nerve impulses and produces a reversible loss of sensation. Lidocaine hydrochloride also exhibits class IB antiarrhythmic effects. The agent decreases the flow of sodium ions into myocardial tissue, especially on the Purkinje network, during phase 0 of the action potential, thereby decreasing depolarization, automaticity and excitability.
The sodium salt form of naproxen, a member of the arylacetic acid group of non-steroidal anti-inflammatory drugs (NSAIDs) with anti-inflammatory analgesic and antipyretic properties. Naproxen sodium reversibly and competitively inhibits cyclooxygenases (COX), thereby blocking the conversion of arachidonic acid to pro-inflammatory prostaglandins. This inhibits the formation of prostaglandins that are involved in pain, inflammation and fever.
The hydrochloride salt form of procyclidine, with anticholinergic properties. Procyclidine hydrochloride competitively binds to striatal cholinergic receptors, thereby diminishing acetylcholine activity and ultimately reducing the frequency and severity of akinesia, rigidity, and tremor associated with uncontrollable body movements. In addition, this agent may block the re-uptake of dopamine by nerve terminals, thereby increasing dopamine activity.
The hydrochloride salt form of promazine, a phenothiazine derivative with antipsychotic and antiemetic properties. Promazine hydrochloride blocks postsynaptic dopamine receptors D1 and D2 in the mesolimbic and medullary chemoreceptor trigger zone (CTZ), thereby decreasing stimulation of the vomiting center in the brain and psychotic effects, such as hallucinations and delusions. In addition, this agent blocks alpha-adrenergic receptors and exhibits strong anticholinergic activity.
The hydrochloride salt form of promethazine, a phenothiazine derivative with antihistaminic, sedative and antiemetic properties. Promethazine hydrochloride selectively blocks peripheral H1 receptors thereby diminishing the effects of histamine on effector cells. Promethazine hydrochloride also blocks the central histaminergic receptors, thereby depressing the reticular system causing sedative and hypnotic effects. In addition, promethazine hydrochloride also has centrally acting anticholinergic properties and probably mediates nausea and vomiting by acting on the medullary chemoreceptive trigger zone.
The combination of pendular nystagmus, head nodding, and torticollis.
The sodium salt form of liothyronine, a synthetic form of the levorotatory isomer of the naturally occurring thyroid hormone triiodothyronine (T3). Liothyronine sodium binds to nuclear thyroid receptors which then bind to thyroid hormone response elements of target genes. As a result, liothyronine sodium induces gene expression that is required for normal growth and development. Liothyronine sodium is more potent and has a more rapid action than thyroxine (T4).
Abnormally decreased volume of circulating fluid (plasma) in body.
Excessive longitudinal ridging that gives the surface of the nail plate a rough appearance. It results from multiple foci of defective keratinization of the proximal nail matrix.
A disorder characterized by an electrocardiographic finding of an organized, regular atrial rhythm with atrial rate between 101 and 240 beats per minute. The P wave morphology must be distinct from the sinus P wave morphology. (CDISC)
An abnormal alignment of the knee backwards that is due to a deformity in the knee joint.
Abnormality of the mitral valve apparatus, whereby chordae attach to a single papillary muscle or hypoplastic papillary muscles.
Individuals with monilethrix have normal hair at birth, but within the first few months of life develop fragile, brittle hair that tends to fracture and produce varying degrees of dystrophic alopecia. In the mildest forms, only the occipital regions of the scalp are involved; however, in severe forms the eyebrows, eyelashes, and secondary sexual hair may also be involved. Follicular hyperkeratosis with predilection for the scalp, nape of neck, and extensor surfaces of the upper arm and thighs is also a characteristic finding in these patients. Light microscopic examination is diagnostic and reveals elliptical nodes of normal thickness and intermittent constrictions (internodes) at which the hair easily breaks. There may be spontaneous improvement with time, especially during puberty and pregnancy, but the condition never resolves completely (summary by Zlotogorski et al., 2006). An autosomal recessive form of monilethrix-like congenital hypotrichosis (see 607903) is caused by mutation in the DSG4 gene (607892). The clinical picture of autosomal recessive monilethrix is more severe than the dominant form, with more extensive alopecia of the scalp, body, and limbs, and a papular rash involving the extremities and periumbilical region (Zlotogorski et al., 2006). The term monilethrix derives from the Latin word for necklace and the Greek for hair (Schweizer, 2006).
A posterior embryotoxon is the presence of a prominent and anteriorly displaced line of Schwalbe.
A congenital fistula in the neck resulting from incomplete closure of a branchial cleft.
A pit or dimple in front of the ear of a newborn is a common finding; rarely, such a dimple may get infected, which will be manifested with redness and swelling and will require medical attention.
A congenital metabolic detected in the neonatal period that is characterized by the presence of a meconium ileus. The disease affects the exocrine glands andis inherited as an autosomal trait. The secretions of exocrine glands are abnormal, resulting in excessively viscid mucus production which causes obstruction of passageways (including pancreatic and bile ducts, intestines, and bronchi). The sweat sodium and chloride content are increased. Symptoms usually appear in childhood and include meconium ileus, poor growth despite good appetite, malabsorption and foul bulky stools, chronic bronchitis with cough, recurrent pneumonia, bronchiectasis, emphysema, clubbing of the fingers, and salt depletion in hot weather.
The organic and psychogenic disturbances observed after closed head injuries (HEAD INJURIES, CLOSED). Post-concussion syndrome includes subjective physical complaints (i.e. headache, dizziness), cognitive, emotional, and behavioral changes. These disturbances can be chronic, permanent, or late emerging.
An unusual presentation of schistosomiasis characterized by a pruritic papular rash in the perigenital or periumbilical area due to an allergic reaction to schistosoma eggs deposited in the skin.
A gurgling sound that comes from the back of the throat of a dying person. It is caused by the build-up of saliva and mucus in the throat and upper airways when the person is too weak to cough.
A type of low-grade glioma with a mixed astrocytoma and oligodendroglioma histology, manifesting with headaches, speech and motor problems, seizures and in some cases subarachnoid haemorrhage.
A hole or opening made through a membrane or other tissue or material.
The passage of an embolus from its site of formation in the arterial system to another location within the circulatory system.
The death of a live-born INFANT within its first year of life.
A developmental defect resulting in complete obliteration of the lumen of the rectum. That is, there is an abnormal closure, or atresia of the tubular structure of the rectum.
A congenital benign lesion that occurs in the distal sternocleidomastoid muscle of infants. It is characterized by the presence of plump spindle cells, and collagenous stroma formation.
A neurologic state characterized by decreased ability to perceive and respond.
The presence of a dilated urinary bladder.
An abnormally increased number of plasma cells in tissues, exudates, or blood
Shortening of the middle parts of the limbs (forearm and lower leg) in relation to the upper and terminal segments.
Morning glory syndrome (MGS) is an optic neuropathy characterized by a congenital funnel shaped excavation of the posterior fundus that incorporates the optic disc malformation (resembling the morning glory flower) MGS is usually unilateral and may result in a decrease in best-corrected visual acuity (BCVA). MGS either occurs isolated or associated to other ocular or non-ocular anomalies.
A laboratory test result which indicates decreased levels of pancreatic enzymes in a biologic specimen.
Acute onset of unresponsiveness or diminished level of consciousness, associated with loss of muscle tone and pallor or cyanosis, that occurs within 48 hours after childhood immunizations. It is primarily associated with pertussis-containing vaccines administered to children under two years of age.
Neoplasm that is growing at a faster rate
An alteration of the septum from the midline.
An elevated concentration of low-density lipoprotein cholesterol in the blood.
A condition characterized by redness, pain, swelling, and tingling in the palms of the hands or the soles of the feet. It may appear as a side effect to chemotherapy agents.
Multiplication or reproduction by cell division of immature precursor cells that have not achieved a fully differentiated state. (NCI)
A form of hydrocephalus in which the flow of cerebrospinal fluid (CSF) within the cerebral ventricular system or in the outlets of the CSF to the arachnoid space is obstructed.
A laboratory test result which indicates increased levels of hemoglobin in a biological specimen.
An X-linked immunodeficiency syndrome that exclusivesly affects males, although females can be carriers. The syndrome is characterized by life-threatening episodes of infectious mononucleosis, hypogammaglobulinemia, and subsequent development of lymphomas (usually B-cell lymphomas) and other lymphoproliferative disorders.
A malignant neoplasm originating from the apical lung. Most malignant superior sulcus neoplasms are bronchogenic carcinomas. This tumor may be associated with Pancoast syndrome. It is also known as Pancoast tumor.
A carcinoma arising from the thyroid gland. It is usually an adenocarcinoma and includes the following main subtypes: follicular, papillary, medullary, poorly differentiated, and anaplastic.
A device that has moved from its original location due to external forces (e.g. stent or lead movement).
Diseases affecting PIGMENTATION, including SKIN PIGMENTATION.
An abnormality of the biliary tree. [HPO:probinson]
Disturbances in sexual desire or performance.
A description of an individual's current and past experience with alcoholic beverage consumption.
An arteritis characterized by the presence of inflammation and necrosis in the arterial wall.
Ewing sarcoma is a cancerous tumor that occurs in bones or soft tissues, such as cartilage or nerves. There are several types of Ewing sarcoma, including Ewing sarcoma of bone, extraosseous Ewing sarcoma, peripheral primitive neuroectodermal tumor (pPNET), and Askin tumor. These tumors are considered to be related because they have similar genetic causes. These types of Ewing sarcoma can be distinguished from one another by the tissue in which the tumor develops. Approximately 87 percent of Ewing sarcomas are Ewing sarcoma of bone, which is a bone tumor that usually occurs in the thigh bones (femurs), pelvis, ribs, or shoulder blades. Extraosseous (or extraskeletal) Ewing sarcoma describes tumors in the soft tissues around bones, such as cartilage. pPNETs occur in nerve tissue and can be found in many parts of the body. A type of pPNET found in the chest is called Askin tumor.Ewing sarcomas most often occur in children and young adults. Affected individuals usually feel stiffness, pain, swelling, or tenderness of the bone or surrounding tissue. Sometimes, there is a lump near the surface of the skin that feels warm and soft to the touch. Often, children have a fever that does not go away. Ewing sarcoma of bone can cause weakening of the involved bone, and affected individuals may have a broken bone with no obvious cause.It is common for Ewing sarcoma to spread to other parts of the body (metastasize), usually to the lungs, to other bones, or to the bone marrow.
Watson syndrome is an autosomal dominant disorder characterized by pulmonic stenosis, cafe-au-lait spots, decreased intellectual ability (Watson, 1967), and short stature (Partington et al., 1985). Most affected individuals have relative macrocephaly and Lisch nodules and about one-third of those affected have neurofibroma (Allanson et al., 1991).
An inherited or acquired, localized or generalized disorder affecting the muscles. It may be associated with abnormalities in the chloride or sodium channels of the muscles. It is characterized by delayed muscle relaxation following stimulation or contraction. Representative examples include myotonia congenita and myotonic dystrophy.
Cervical canal (i.e., uterine cervix) dilators consisting of an expansible plug (i.e., a tent) of dried Laminaria (a genus of seaweeds); they are usually available as sterilized devices that have a strong thread attached for anchoring and easy removal. These tents gradually swell to several times their original diameter by the absorption of moisture from the cervix in a period of several hours (typically 12 to 14), producing a gradual cervical dilatation. Laminaria tent cervical dilators are used to perform intrauterine obstetric maneuvers, especially to perform midterm abortions.
A rare slow-growing benign neoplasm arising from the soft tissues in children. It is a poorly circumscribed tumor characterized by the presence of chondrocyte-like cells, nodular calcification, nuclear palisading, and in some cases osteoclastic giant cells.
Breathing that requires observed effort or an increased amount of energy.
Decreased concentration of fibrinogen in the blood.
Hemorrhage into the parenchyma of the brain.
impairment of health or a condition of abnormal functioning of a region of the pharynx that is below the soft palate and above the epiglottis and is continuous with the mouth.
A hereditary or acquired blood disorder characterized by the presence of smaller than normal, sphere-shaped erythrocytes. It results in hemolytic anemia and splenomegaly.
A carcinoma arising from the squamous cells of the epidermis. Skin squamous cell carcinoma is most commonly found on sun-exposed areas. The majority of the tumors are well-differentiated.
Presence of CALCIUM PYROPHOSPHATE in the connective tissues such as the cartilaginous structures of joints. When accompanied by GOUT-like symptoms, it is referred to as pseudogout.
Loss of or impaired ability to smell. This may be caused by OLFACTORY NERVE DISEASES; PARANASAL SINUS DISEASES; viral RESPIRATORY TRACT INFECTIONS; CRANIOCEREBRAL TRAUMA; SMOKING; and other conditions.
A condition characterized by the thickening of the ventricular ENDOCARDIUM and subendocardium (MYOCARDIUM), seen mostly in children and young adults in the TROPICAL CLIMATE. The fibrous tissue extends from the apex toward and often involves the HEART VALVES causing restrictive blood flow into the respective ventricles (CARDIOMYOPATHY, RESTRICTIVE).
The enteric villi are atrophic or absent. [HPO:probinson]
Abnormality of the absorption of fat from the gastrointestinal tract.
Interruption of the blood supply to a portion of the placenta, resulting in ischemic necrosis.
Infections with bacteria LEPTOSPIRA CANICOLA.
A pale yellow discoloration of the optic disk (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
Abnormal slowness of thought processes. [PMID:25850732]
Abnormally rapid thoughts with or without abrupt changes from one topic to another.
Indicates a person currently joined in a legally binding matrimonial union. Classify common law marriage as married. Includes married couples living together and not living together.
The recurrent, measured movements (rhythm) of a beating heart in a fetus.
A histologic variant of basal cell carcinoma of the skin characterized by the presence of strands and nests of malignant cells that are embedded in a dense fibrotic stroma.
A rare fibro-osseous lesion of the jaw that predominantly affects middle-aged women of African descent. It is generally asymptomatic or may manifest with pain and gingival swelling. Multiple dense lobulated bone lesions often symmetrical are located in various regions of the jaw and can be seen on radiological examination.
A grade III or grade IV glioma arising from the central nervous system. This category includes glioblastoma, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma.
A lesion characterized by the presence of neoplastic neuroepithelial cells with palisading nuclei. This lesion implies a morphologic growth pattern and it is not considered a clinicopathological entity.
A rare benign neuroectodermal tumor originating from olfactory receptor cells in the nasal cavity. Microscopically, it is characterized by the absence of malignant characteristics and the absence of rosettes formation.
Chiari malformation type II (CM2), also known as the Arnold-Chiari malformation, consists of elongation and descent of the inferior cerebellar vermis, cerebellar hemispheres, pons, medulla, and fourth ventricle through the foramen magnum into the spinal canal. CM2 is uniquely associated with myelomeningocele (open spina bifida; see 182940) and is found only in this population (Stevenson, 2004). It is believed to be a disorder of neuroectodermal origin (Schijman, 2004). For a general phenotypic description of the different forms of Chiari malformations, see Chiari malformation type I (CM1; 118420).
A polyunsaturated very long-chain fatty acid with a 22-carbon backbone and 6 double bonds. Four separate isomers can be called by this name.
An abnormality of the ability (skills) to perform a precise movement of large muscles with the intent to perform a specific act. Gross motor skills are required to mediate movements of the arms, legs, and other large body parts.
An individual who drinks from time to time, but generally less than once per week.
An individual who drinks at least once per week with regularity.
operating a vehicle (automobile, truck, boat, plane, bicycle, etc) while under the influence of alcohol or other illicit drugs.
abusive administration of a substance intranasally or by breathing it into the lungs from the surrounding air.
An individual's total number of brothers and sisters.
An indication that an individual is living in the home of a friend.
Living with family. Maps to PD1-2 Living arrangement (IS) 00742 [F].
A demographic parameter indicating the amount of earnings made by a family.
Indicates that a person has never attended an educational program or formal schooling.
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. [DDD:hvfirth, HPO:sdoelken]
An unwelcome and persistent idea, image or thought that is upsetting to an individual.
Written or spoken words that are excessively critical, insulting, and/or intimidating.
Confusion in mental picture of one's physical self.
A person who was assigned to one gender at birth based on physical characteristics but who self-identifies psychologically and emotionally as the other.
Softening and whitening of the skin due to excessive moisture.
The pores are visible but not large. The skin texture is neither fine or thick and it neither feels dry or oily to the touch.
A question about whether an individual chokes or has choked when swallowing.
Appropriate adjustment of prevailing emotional tone in response to circumstances
Gastroenteritis resulting from a bacterial infection.
A malignant tumor arising from the epithelium that covers the tongue. The vast majority of tongue carcinomas are moderately or poorly differentiated squamous cell carcinomas.
A carcinoma that arises from the hard or soft palate. Representative examples include squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma.
A carcinoma arising from the tonsilar epithelium.
A melanoma that arises from the structures of the eye or ocular adnexa.
A non-neoplastic or neoplastic disorder that affects the anatomic structures of the neck region. This category includes disorders of the pharynx, larynx, thyroid gland, and parathyroid gland.
Lack of contraction of abdominal muscles in the quadrant of the abdomen that is stimulated by scraping the skin tangential to or toward the umbilicus. [PMID:12531937, PMID:24785227]
Absence of the knee jerk reflex, which can normally be elicited by tapping the patellar tendon with a reflex hammer just below the patella.
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
Chronic or recurrent gastrointestinal disorders without an identifiable structural or biochemical explanation by the routine diagnostic tests. Functional gastrointestinal disorders are classified according to the presumed site of the disorder, such as IRRITABLE BOWEL SYNDROME, non-ulcer DYSPEPSIA, and non-cardiac CHEST PAIN.
An abnormality in which the cardiac ventricles depolarize too early as a result of an abnormality of cardiac conduction pathways such as an accessory pathway.
A rare spinal tumor which is highly malignant and tends to be locally invasive of surrounding neural tissue. The tumor also tends to spread throughout the neuroaxis and is often rapidly progressive. Histologically the tumors are highly cellular with nuclear and cellular pleomorphism, endothelial proliferation, mitotic figures, and, often, necrosis. This tumor has a relatively poor prognosis. Clinical features may include pain followed by rapidly progressive neurologic deficits such as extremity weakness, sensory changes, spasticity, and incontinence. (From Innocenzi et al., Clin Neurol Neurosurg 1997 Feb;99(1):1-5)
Symptoms, physical examination results, and/or laboratory test results related to the endocrine system.
A neuroblastoma arising from the cerebral hemispheres.
A teratoma arising in the sacro-coccygeal region.
A neuroblastoma arising from the adrenal gland.
Allergic reaction to eggs that is triggered by the immune system.
Allergic reaction to peanuts that is triggered by the immune system.
A condition characterized by cardiorespiratory and neurological depression following birth.
A rare syndrome characterized by the presence of omphalocele, anterior diaphragmatic hernia, sternal cleft, ectopia cordis, and ventricular septal defect or left ventricle diverticulum.
Any noxious and unintended response(s) to a medical product or procedure, for which a causal relationship with this product or procedure is at least a reasonable possibility i.e., the relationship cannot be ruled out.
Symptoms, signs, diagnostic examinations or a test results in a pregnant mother.
A rupture in the ileal wall due to traumatic or a pathologic processes.
A response indicating that an individual is or was unable to walk.
The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissible to another susceptible host.
The maintenance of a stable, upright body position.
IgA nephropathy secondary to hepatobiliary disease.
Personal actions to change own body position independently with or without assistive device
Memory of events without specific awareness of learning or experiencing the event.
The presence of a fistula between the bowel and the perineum.
A circumferential measurement of the largest part of the upper arm.
Comprises a set of group dynamics whereby a group in which one feels comfortable may override personal habits, individual moral inhibitions or idiosyncratic desires to impose a group norm of attitudes and/or behaviors.
Child or adult subjected to nonaccidental physical, emotional, or sexual violence or injury.
Personal actions to perform the most basic physical tasks and personal care activities independently with or without assistive device
Formation of and investment in significant relationships. Usually refers to the emotional and biological attachment of human or animal infants to caretaking figures.
Personal actions to perform basic personal care activities and instrumental activities of daily living
The ability to sit in a bath and perform activities of bathing.
The ability to stand in a bath and perform activities of bathing.
The ability to kneel in a bath and perform activities of bathing.
Personal actions to toilet self independently with or without assistive device
Cognitive and emotional processes encompassing magnification of pain-related stimuli, feelings of helplessness, and a generally pessimistic orientation.
Susceptible to localized injury to the skin and/or underlying tissue usually over a bony prominence as a result of pressure, or pressure in combination with shear (NPUAP, 2007).
A squamous cell carcinoma or less frequently an adenocarcinoma, often associated with human papillomavirus (HPV) infection. Homosexual men are at particular risk. The most important prognostic factors are tumor stage and nodal status.
Inflammation of the stomach resulting from viral infection.
Displacement of the urethral opening on the dorsal (superior) surface of the penis.
Loss of the ability to perceive and process pain.
Acute promyelocytic leukemia in which the promyelocytes in the peripheral blood have paucity or absence of cytoplasmic granules and characteristic bilobed nuclei.
Increased chance of taking one's life intentionally
Production of sounds by means of vocal cord vibrations.
A question about the reason why an individual did not prepare meals.
A state of abnormally elevated or irritable mood, arousal, and or energy levels. [PMID:15104084]
Severity of manifested apprehension, tension, or uneasiness arising from an unidentifiable source
Acute appendicitis with gangrenous changes resulting in the rupture of the appendiceal wall. The appendiceal wall rupture causes the release of inflammatory and bacterial contents from the appendiceal lumen into the abdominal cavity.
Increased blood pressure during a pregnancy.
Personal actions to care for own mouth and teeth independently with or without assistive device
Decreased, delayed, or absent ability to receive, process, transmit, and/or use a system of symbols.
A response indicating that an individual is unable to do feed themself.
Primary sclerosing cholangitis (PSC) is a slowly progressive cholestatic liver disease characterized by fibroobliterative inflammation of the biliary tract, leading to cirrhosis and portal hypertension. It is a major indication for liver transplantation (Sheth et al., 2003). Approximately 75 to 80% of PSC cases are associated with inflammatory bowel disease (IBD; see 266600), and 2.5 to 7.5% of patients with IBD develop PSC (Lee and Kaplan, 1995).
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech.
Clinical and laboratory findings about the umbilical cord.
A narrowing of the sacrosciatic notch, i.e., the deep indentation in the posterior border of the hip bone at the point of union of the ilium and ischium.
An indication that an individual's uterus is present.
A consistent rhythmic pattern of uterine muscle tightening that occurs at regular intervals for the same duration of time.
An uterine contraction that is barely felt.
Type 1 diabetes mellitus in which there are frequent, clinically significant fluctuations in blood glucose levels both above and below levels expected to be achieved by available therapies.
The accumulation of fluid in the feet, most prominently on the dorsum.
Partial or complete obstruction of the duodenal lumen due to the presence of a membranous web.
A type of Macrodactyly affecting one or several fingers.
The cerebral creatine deficiency syndromes (CCDS), inborn errors of creatine metabolism, include the two creatine biosynthesis disorders, guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT) deficiency, and the creatine transporter (CRTR) deficiency. Intellectual disability and seizures are common to all three CCDS. The majority of individuals with GAMT deficiency have a behavior disorder that can include autistic behaviors and self-mutilation; about 40% have movement disorder. Onset is between ages three months and three years. Only 14 individuals with AGAT deficiency have been reported. The phenotype of CRTR deficiency in affected males ranges from mild intellectual disability and speech delay to severe intellectual disability, seizures, movement disorder and behavior disorder; age at diagnosis ranges from two to 66 years. Clinical phenotype of females heterozygous for CRTR deficiency ranges from asymptomatic to severe phenotype resembling male phenotype.
Barth syndrome is characterized in affected males by cardiomyopathy, neutropenia, skeletal myopathy, prepubertal growth delay, and distinctive facial gestalt (most evident in infancy); not all features may be present in a given patient. Cardiomyopathy, which is almost always present before age five years, is typically dilated cardiomyopathy with or without endocardial fibroelastosis (EFE) or left ventricular noncompaction (LVNC); rarely it is hypertrophic cardiomyopathy (HCM). Heart failure is a significant cause of morbidity and mortality; risk of arrhythmia and sudden death is increased. Neutropenia is most often associated with mouth ulcers, pneumonia, and sepsis. The non-progressive myopathy predominantly affects the proximal muscles, and results in early motor delays. Prepubertal growth delay is followed by a post-pubertal growth spurt with remarkable ""catch-up"" growth. Heterozygous females who have a normal karyotype are asymptomatic and have normal biochemical studies.
OPA3-related 3-methylglutaconic aciduria is characterized by optic atrophy and/or choreoathetoid movement disorder with onset before age ten years. Optic atrophy is associated with progressive, decreased visual acuity within the first years of life, sometimes associated with infantile-onset horizontal nystagmus. Most individuals have chorea, often severe enough to restrict ambulation. Some are confined to a wheelchair from an early age. Although most individuals develop spastic paraparesis, mild ataxia, and occasional mild cognitive deficit in their second decade, the course of the disease is relatively stable.
The presence of solitary or multiple stones in the intrahepatic bile ducts.
Symptoms of disorders of the lower urinary tract including frequency, NOCTURIA; urgency, incomplete voiding, and URINARY INCONTINENCE. They are often associated with OVERACTIVE BLADDER; URINARY INCOMPETENCE; and INTERSTITIAL CYSTITIS. Lower urinary tract symptoms in males were traditionally called PROSTATISM.
Sudden and sustained deterioration of the kidney function with decreased glomerular filtration rate, and concommittant necrosis of the renal papillae; representative causes include sickle cell disease, heave analgesic use, diabetes mellitus, and pyelonephritis.
The date (and time) on which the event began.
An out-pouching of the calyx into the renal parenchyma.
Inflammation of the SACROILIAC JOINT. It is characterized by lower back pain, especially upon walking, fever, UVEITIS; PSORIASIS; and decreased range of motion. Many factors are associated with and cause sacroiliitis including infection; injury to spine, lower back, and pelvis; DEGENERATIVE ARTHRITIS; and pregnancy.
The ability of the knee to move past its normal range of motion, (knee hyperextension is greater than 10 degrees).
Spastic weakness affecting all four limbs.
Painful sensation felt when pressure is applied to the muscles.
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.
A finding referring to walking difficulties.
Have you ever felt dizzy, lightheaded, or as if the room is spinning around you? If the feeling happens often, it could be a sign of a balance problem. Balance problems can make you feel unsteady. You may also have blurred vision, confusion, and disorientation. They are one cause of falls and fall-related injuries, such as a hip fracture. Some balance problems are due to problems in the inner ear. Others may involve another part of the body, such as the brain or the heart. Aging, infections, head injury, certain medicines, or problems with blood circulation may also cause balance problems. It is important to see your doctor about balance problems. They can be a sign of other health problems, such as an ear infection or a stroke. Your doctor may send you to a specialist for a diagnosis. You may need a hearing test, blood tests, or imaging studies of your head and brain. Other possible tests look at your eye movements, and how your body responds to movement. In some cases, treating the illness that is causing the disorder will help with the balance problem. Exercises, a change in diet, and some medicines also can help. NIH: National Institute on Deafness and Other Communication Disorders.
Symptoms, physical examination results, and/or laboratory test results related to the head and neck.
Noises from the temporomandibular joint during mandibular movement (e.g., chewing). Temporomandibular joint crepitus is often described as a clicking, popping, grating sound.
A congenital or acquired deformity of the spine. Representative examples include scoliosis, kyphosis, and sagittal imbalance.
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Exaggerated convexity of the cervical vertebral column, causing the cervical spine to bow outwards and take on a rounded appearance.
Increased inferior to superior extent of the thorax.
Decreased inferosuperior length of the sternum.
Abnormal increase in size of the upper limbs (due to an increase of the size of cells).
Abnormally reduced diameter (cross section) of the clavicles.
Active range of motion of the shoulder with self-initiated movement
Active range of motion of the elbow with self-initiated movement
Active range of motion of the wrist with self-initiated movement
An abnormal position of the hand in which the wrist is bent toward the radius (i.e., toward the thumb).
Significant reduction in both length and girth of the finger compared to the contralateral finger, or alternatively, compared to a typical finger size for an age-matched individual.
Active range of motion of the fingers with self-initiated movement
Bending or curvature of a thumb towards the ulnar side (towards the ring finger).
Active range of motion of the hip with self-initiated movement
An inward slant of the thigh in which the knees are close together and the ankles far apart. Genu valgum can develop due to skeletal and joint dysplasias (e.g., OSTEOARTHRITIS; HURLER SYNDROME); and malnutrition (e.g., RICKETS; FLUORIDE POISONING).
Active range of motion of the knee with self-initiated movement
Active range of motion of the ankle with self-initiated movement
Increased back to front length of the foot.
A foot for which the measured width is below the 5th centile for age; or, a foot that appears disproportionately narrow for its length.
Occurs either when an infant shows no interest in feeding or when there is an inability to take in adequate nutrition. Poor feeding is a nonspecific symptom of many disorders, including neurological, genetic, structural, metabolic, and infectious diseases.
A sudden, electric shock sensation that is triggered by flexion of the neck, and which travels down the spine, arms, legs, and sometimes trunk.
An abnormal growth located in the esophagus.
An abnormal growth located in the stomach.
Testicular Tenderness: abnormal tenderness of the testicles to light palpation. Can be a manifestation of vasculitis.
Congenital lack of the skin of prepuce of penis, that is, of the double-layered fold of skin and mucous membrane that covers the glans penis.
A benign or malignant pathologic structure in any part of the body, resulting from a neoplastic accumulation of cells, inflammatory cells, or cystic changes.
Allergic reaction to tree nuts that is triggered by the immune system.
Allergic reaction to SHELLFISH or shellfish products.
Latex allergy is an IgE-mediated immediate hypersensitivity response to natural rubber latex (NRL) protein with a variety of clinical signs ranging from contact urticaria, angioedema, asthma, and anaphylaxis. [PMID:15327474]
Weakness of the quadriceps muscle (that is, of the muscle fasciculus of quadriceps femoris).
A carcinoma that arises from the transitional epithelium of the ureter. It is associated with tobacco use and usually presents with gross or microscopic hematuria.
Adenocarcinoma that is spread throughout the body.
Chemical agents that increase the permeability of CELL MEMBRANES to POTASSIUM ions.
Chemical agents that increase the permeability of CELL MEMBRANES to SODIUM ions.
Any abnormal noise generated by the beating heart. []
The result of a body mass index measurement.
Reduced width of the skin of vermilion border region of upper lip.
Diarrhea that is associated with current or recent antibiotic use.
A question about the ability of an individual to get on and off the toilet.
Personal actions to move from place to place in a wheelchair
Presence of multiple polyps in the duodenum.
Skin dimples are cutaneous indentations that are the result of tethering of the skin to underlying structures (bone) causing an indentation.
Swelling due to an excessive accumulation of fluid in trunk area.
Symptoms, physical examination results, and/or laboratory test results related to the eye.
A clinical finding indicating the enlargement of the lymph nodes in the axillary region. It may be caused by infections, systemic diseases, or cancer.
Urticaria characterized by spontaneously recurring hives for 6 weeks or longer. [PMID:25807072]
Inflammation, or an inflammatory state in the large intestine.
Ability to change body location independently with or without assistive device
A response indicating that an individual lacks sitting balance and is unable to sit or transfer.
The person actively helps with dressing, they may lift their feet for a pant opening or a child may help by pushing their arm through a sleeve.
The person may not be able to actively assist but they act jointly to being dressed and do not, for example, fight the caretaker.
A deviation from the normal range of neutrophil cell counts in the circulation.
Abnormal number of platelets per volume of blood. In a healthy adult, a normal platelet count is between 150,000 and 450,000 per microliter of blood.
An anomaly in the number of monocytes, which are myeloid mononuclear recirculating leukocyte that can act as a precursor of tissue macrophages, osteoclasts and some populations of tissue dendritic cells.
An anomaly of the circulating level of luteinizing hormone (LH).
An anomalous concentration of testosterone in the blood. []
Number of leukocytes per volume of blood beyond normal limits.
An anomaly of the number of basophils per volume in the blood circulation. []
A deviation from the normal range of the average amount of hemoglobin per red blood cell (27 to 31 picograms/cell). A reduced mean corpuscular hemoglobin (MCH) may indicate a hypochromic anemia, but the MCH may be normal if both the total hemoglobin and the red blood cell count are reduced.
Any abnormality in the total number of lymphocytes in the blood.
An indication that a patient requests to terminate pregnancy.
A question about an individual's ability to tie shoe laces.
Loose and sagging skin often associated with loss of skin elasticity.
Repeated infections of the urinary bladder.
There was greater than or equal to 50% stenosis (reduction in cross-sectional area) in two coronary arteries (or greater than or equal to 50% stenosis in the left main coronary artery). (ACC)
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Improper use of prescription drugs or medications outside the intended purpose, scope, or guidelines for use.
An infectious process affecting the penis.
A type of insomnia characterized by waking up (too) early in the morning.
Total inability to hear sounds in one or both ears.
Increased change of contamination with disease-producing germs
An abnormal communication between the jejunum and another organ or cavity.
Increased chance of accidental tissue injury
Abnormal narrowing of the choana (the posterior nasal aperture).
An abnormality that refers to mutation of factor V Leiden, which is a variant of human factor V. It results in thrombophilia, deep vein thrombosis, and a slightly increased risk of miscarriage.
holding or keeping within the stomach matter which is normally moved on.
state of altered reactivity in which the body reacts with an exaggerated or inappropriate immune response to a chemical substance having the properties of an antigen or hapten that is in contact with the skin, the resulting skin condition being allergic contact dermatitis.
A squamous cell carcinoma arising from the oral cavity. It affects predominantly adults in their fifth and sixth decades of life and is associated with alcohol and tobacco use. Human papillomavirus is present in approximately half of the cases. It is characterized by a tendency to metastasize early to the lymph nodes. When the tumor is small, patients are often asymptomatic. Physical examination may reveal erythematous or white lesions or plaques. The majority of patients present with signs and symptoms of locally advanced disease including mucosal ulceration, pain, difficulty with speaking, chewing, and swallowing, bleeding, weight loss, and neck swelling. Patients may also present with swollen neck lymph nodes without any symptoms from the oropharyngeal tumor. The most significant prognostic factors are the size of the tumor and the lymph nodes status.
A usually aggressive malignant bone-forming mesenchymal neoplasm arising from the bone. It may arise de novo or from a pre-existing lesion of the bone. Pain and a palpable mass are the most frequent clinical sign and symptom. It may spread to other anatomic sites, particularly the lungs.
A small round cell bone tumor that lacks morphologic, immunohistochemical, and electron microscopic evidence of neuroectodermal differentiation. It represents one of the two ends of the spectrum called Ewing sarcoma/peripheral neuroectodermal tumor. It often affects the diaphysis or metaphyseal-diaphyseal portion of long bones. Clinical findings include pain and a mass in the involved area. Fever, anemia, leukocytosis, and an increased sedimentation rate are often seen. X-ray examination reveals osteolytic lesions. The prognosis depends on the stage, anatomic location, and size of the tumor.
A very rare, locally aggressive, malignant neoplasm of the hair follicle. The majority of the cases arise de novo, however malignant transformation from a pre-existing pilomatricoma has been reported. It usually presents as a solitary nodule in the head and neck, upper extremities, or buttocks. Morphologically, it is characterized by the presence of aggregates of basaloid cells infiltrating the dermis. Masses of ghost cells are present in the cellular aggregates. Complete surgical excision is the treatment of choice. If it is not completely removed, it usually recurs, but it rarely metastasizes to distant anatomic sites.
Downbeat nystagmus is a type of fixation nystagmus with the fast phase beating in a downward direction. It generally increases when looking to the side and down and when lying prone.
In primary position, the eyes drift slowly downward and then spontaneously beat upward. Upward gaze accentuates the nystagmus. The associated oscillopsias are often very irritating, but the symptoms are usually transient.
A malignant neoplasm that affects the epiglottis. The vast majority of cases are squamous cell carcinomas.
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Mild, moderate, or severe dysplasia of the squamous epithelium of the laryngeal mucosa.
A condition where seizures occur in association with ethanol abuse (ALCOHOLISM) without other identifiable causes. Seizures usually occur within the first 6-48 hours after the cessation of alcohol intake, but may occur during periods of alcohol intoxication. Single generalized tonic-clonic motor seizures are the most common subtype, however, STATUS EPILEPTICUS may occur. (Adams et al., Principles of Neurology, 6th ed, p1174)
A lesion that is characterized by architectural and cytologic abnormalities of the esophageal epithelium, and carries a predisposition for progression to invasive carcinoma. Intraepithelial neoplasia (dysplasia) of the esophagus is graded as low or high grade. In this two-tier system, severe dysplasia and carcinoma in situ are included under the rubric of high grade intraepithelial neoplasia and may have the same clinical implications. (WHO, 2000) -- 2003
A lesion in which the architectural and cytologic abnormalities are confined to the lower half of the esophageal epithelium. (WHO, 2000) -- 2003
A morphologic finding indicating the presence of moderate dysplastic cellular changes and moderate architectural changes in the epithelium of the esophageal mucosa. There is no evidence of invasion.
A neoplastic, non-invasive lesion that affects the biliary epithelium. It is characterized by the presence of atypical epithelial cells with an increased nuclear/cytoplasmic ratio, nuclear hyperchromasia, and loss of nuclear polarity.
A pancreatic mucinous intraepithelial neoplasia characterized by the presence of papillary and less often flat architectural patterns. Moderate cytological atypia is present with some loss of nuclear polarity, nuclear crowding or hyperchromatism.
A morphologic finding indicating the presence of mild dysplastic cellular changes and mild architectural changes in the glandular epithelium of the colonic mucosa. There is no evidence of invasion.
A morphologic finding indicating the presence of moderate dysplastic cellular changes and moderate architectural changes in the glandular epithelium of the colonic mucosa. There is no evidence of invasion.
A morphologic finding indicating the presence of dysplastic glandular epithelial cells in the rectal mucosa. There is no evidence of invasion.
A morphologic finding indicating the presence of mild dysplastic cellular changes and mild architectural changes in the glandular epithelium of the rectal mucosa. There is no evidence of invasion.
A morphologic finding indicating the presence of moderate dysplastic cellular changes and moderate architectural changes in the glandular epithelium of the rectal mucosa. There is no evidence of invasion.
Overproduction of thyroid-stimulating hormone (TSH) by the anterior pituitary gland.
An abnormal growth that projects from the mucous membrane of the urinary bladder.
A power of attorney is a legal document that gives one person (such as a relative, lawyer, or friend) the authority to make legal, medical, or financial decisions for another person. It may go into effect right away, or when that person is no longer able to make decisions for himself or herself.
A highly contagious viral infection caused by the varicella zoster virus. Clinically, it may be manifested as shingles or chicken pox.
An abnormal growth located in the hilum of the lung.
A cystic structure in the tonsillar tissue.
Reduced strength and weakness of the muscles of the arms and legs.
Costello syndrome is characterized by failure to thrive in infancy as a result of severe postnatal feeding difficulties; short stature; developmental delay or intellectual disability; coarse facial features (full lips, large mouth, full nasal tip); curly or sparse, fine hair; loose, soft skin with deep palmar and plantar creases; papillomata of the face and perianal region; diffuse hypotonia and joint laxity with ulnar deviation of the wrists and fingers; tight Achilles tendons; and cardiac involvement including: cardiac hypertrophy (usually typical hypertrophic cardiomyopathy [HCM]), congenital heart defect (usually valvar pulmonic stenosis), and arrhythmia (usually supraventricular tachycardia, especially chaotic atrial rhythm/multifocal atrial tachycardia or ectopic atrial tachycardia). Relative or absolute macrocephaly is typical, and postnatal cerebellar overgrowth can result in the development of a Chiari I malformation with associated anomalies including hydrocephalus or syringomyelia. Individuals with Costello syndrome have an approximately 15% lifetime risk for malignant tumors including rhabdomyosarcoma and neuroblastoma in young children and transitional cell carcinoma of the bladder in adolescents and young adults.
A state of the information pertaining to the entity associated with a clinical study protocol indicating whether this information is active or inactive for the purpose of inclusion in the protocol planned activities.
A laboratory test result indicating abnormal cells found in the urine sample.
A well-circumscribed, lobulated tumor, completely or partially covered by a fibrous capsule. It usually arises in the fingers. It is characterized by the presence of mononuclear cells, multinucleated osteoclast-like giant cells, hemosiderin-laden macrophages, foam cells, and an inflammatory infiltrate. The tumor is slow-growing, usually developing over several years. Clinical presentation includes painless edema of the affected site.
An infectious process involving an implanted medical device and the surrounding tissues.
A non-metastasizing neoplasm arising from the lung parenchyma, bronchial tree, or trachea. Representative examples include lung hamartoma, lung papilloma, and tracheal leiomyoma.
Tooth can be moved less than 1mm in the buccolingual or mesiodistal direction.
Tooth can be moved 1mm or more in the buccolingual or mesiodistal direction. No mobility in the occlusoapical direction (vertical mobility).
Tooth can be moved 1mm or more in the buccolingual or mesiodistal direction. Mobility in the occlusoapical direction is also present (vertical mobility).
The hydrochloride salt form of imipramine, a synthetic tricyclic derivative, antidepressant Imipramine enhances monoamine neurotransmission in certain areas of the brain. It also induces sedation through histamine 1 receptor blockage; hypotension through beta-adrenergic blockage; and diverse parasympatholytic effects. Imipramine has less sedative effect than other members of its therapeutic family. It is used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. (NCI04)
A combination preparation composed of the adrenergic beta-1 receptor antagonist atenolol and thiazide-like diuretic chlorthalidone, with anti-hypertensive activity. Atenolol selectively binds to beta-1 adrenergic receptors in the heart and vascular smooth muscle, thereby inhibiting sympathetic stimulation. This results in a decrease in cardiac rate and muscle contractility, thereby reducing cardiac output. As a diuretic, chlorthalidone directly inhibits sodium and chloride reabsorption on the luminal membrane of the early segment in the distal convoluted tubule (DCT) in the kidney. This leads to an increase in sodium, chloride, bicarbonate, and potassium secretion and results in the excretion of water. Together, these agents lead to a reduction in blood pressure.
brand name of metformin an anti-diabetic drug
The hydrochloride salt form of dicyclomine, a synthetic analog of acetylcholine with antimuscarinic activity. Dicyclomine hydrochloride antagonizes muscarinic receptors on smooth muscle in the gastrointestinal (GI) tract, thereby preventing the actions of acetylcholine and reducing GI smooth muscle spasms.
Any substance that inhibits aromatase, an enzyme responsible for the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. Inhibition of aromatase results in the suppression of estrogen-regulated processes.
Any substance that inhibits topoisomerase-I, a topoisomerase that relieves torsional stress in a DNA molecule by cutting only one strand of the DNA double helix. Inhibition of topoisomerase-I causes DNA damage, inhibition of DNA replication, and apoptosis.
The hydrochloride salt of a semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. Because ongoing DNA synthesis is necessary for irinotecan to exert its cytotoxic effects, it is classified as an S-phase-specific agent.
Compounds and drugs that inhibit or block the activity of CATECHOL O-METHYLTRANSFERASE enzymes. Drugs in this class are used in management of central nervous system disorders such as PARKINSON DISEASE.
The disodium salt form of balsalazide, an aminosalicylate and oral prodrug that is enzymatically cleaved in the colon to produce the anti-inflammatory agent mesalazine. Mesalazine acts locally on the mucosa of the colon where it diminishes inflammation by blocking the production of arachidonic acid metabolites, including leukotrienes, prostaglandins and hydroxyeicosatetraenoic acids, and other inflammatory agents. Balsalazide disodium is used to treat chronic inflammatory bowel disease.
A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.
A form of self harm in which someone mimics the act of suicide without the intent to kill themselves.
Lower than normal levels of phosphates in the circulating blood.
An abnormally decreased chloride concentration in the blood.
Toxicity that impairs or damages the kidney. This condition is often caused by the administration of a pharmaceutical agent that causes damage to the kidney.
A fetus of at least 20 weeks gestation, or of a birth weight of at least 350 grams if the gestational age is unknown, that is born without signs of life at the time of delivery, and with an Apgar score of zero at both one and five minutes.
Absence seizures characterized by insidious begin and end and often prolonged duration, accompanied by slow spike-wave discharges on EEG.
An infection that is due to human herpesvirus (HHV) types 6 or 7; it is characterized by 3-5 days of high fever followed by the acute onset of a rosy, pink, non-pruritic, macular rash that is predominantly on the neck and trunk.
A belladonna alkaloid derivative and the levorotatory form of racemic atropine isolated from the plants Hyoscyamus niger or Atropa belladonna, which exhibits anticholinergic activity. Hyoscyamine functions as a non-selective, competitive antagonist of muscarinic receptors, thereby inhibiting the parasympathetic activities of acetylcholine on the salivary, bronchial, and sweat glands, as well as the eye, heart, bladder, and gastrointestinal tract. These inhibitory effects cause a decrease in saliva, bronchial mucus, gastric juices, and sweat. Furthermore, its inhibitory action on smooth muscle prevents bladder contraction and decreases gastrointestinal motility.
The sulfate salt of atropine, a naturally-occurring alkaloid isolated from the plant Atropa belladonna. Atropine functions as a sympathetic, competitive antagonist of muscarinic cholinergic receptors, thereby abolishing the effects of parasympathetic stimulation. This agent may induce tachycardia, inhibit secretions, and relax smooth muscles. (NCI04)
A synthetic derivative of quinolyl with chemotherapeutic and antibiotic properties, Hydroxychloroquine Sulfate acts against erythrocytic malarial parasites (Plasmodium vivax, ovale, and malariae) by concentrating in food vacuoles. It inhibits plasmodial heme polymerase and acts through other unknown mechanisms. Hydroxychloroquine also has anti-inflammatory properties and is used in the treatment of rheumatoid arthritis and lupus erythematosus. (NCI04)
The tartrate salt form of levorphanol, a synthetic phenanthrene with potent opioid analgesic activity. Levorphanol tartrate mimics the actions of endogenous peptides at CNS opioid receptors, thereby producing the characteristic morphine-like effects on the mu-opioid receptor, including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia and physical dependence.
A malocclusion of the teeth in which maxillary incisor and canine teeth project over the mandiblar teeth. The overlap is measured parallel to the occlusal plane and therefore is called horizontal overlap.
The transfer of ADP-ribose to amino acids within proteins or to the amino group at N2 of a 2'-deoxyguanosine residue in double-stranded DNA.
A benign or malignant (primary or metastatic) neoplasm affecting the adrenal medulla. (NCI05)
Amino Acid Biosynthesis consists of cellular enzymatic reactions that produce amino acids, organic compounds containing an amino and a carboxyl group and often used in protein synthesis by the formation of peptide bonds during ribosomal translation of mRNA. Several important amino acids, such as the neurotransmitter g-aminobutyric acid, have other functions than protein synthesis.
Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.
Any substance that treats, prevents, or inhibits the development of leukemia.
A disorder associated with three or more of the following: eating until feeling uncomfortably full; eating large amounts of food when not physically hungry; eating much more rapidly than normal; eating alone due to embarrassment; feeling of disgust, DEPRESSION, or guilt after overeating. Criteria includes occurrence on average, at least 2 days a week for 6 months. The binge eating is not associated with the regular use of inappropriate compensatory behavior (i.e. purging, excessive exercise, etc.) and does not co-occur exclusively with BULIMIA NERVOSA or ANOREXIA NERVOSA. (From DSM-IV, 1994)
The metabolically-active portion of calcium, not bound to proteins, circulating in the blood.
Pain that may be caused by or related to cellular, tissue, and systemic changes that occur during NEOPLASM growth, tissue invasion, and METASTASIS.
A pathological process in which normal cells are transformed into malignant cancer cells within a primary tumor.
Pathological conditions of the CARDIOVASCULAR SYSTEM caused by infections.
obstruction or closure which causes impairment of blood flow in the arteries and veins which supply the brain.
The study of the processes by which normal cells are transformed into cancer cells by chemicals.
A drug that makes tumor cells more sensitive to the effects of chemotherapy.
pathologic condition existing at, and usually before, birth affecting the brain, which is composed of the intracranial components of the central nervous system.
An abnormality of the digestive system that is present at birth or detected in the neonatal period.
drugs used to cause dilation of the coronary blood vessels.
The adverse effect of some iatrogenic therapies. It is an accepted side effect in radiation therapy where the desired effect is to kill rapidly growing tumor cells. In the killing of tumor cells, other cells that are rapidly growing e.g hair, mucous membranes are also killed.
substance or agent which suppresses, prevents or opposes the activity of elastase.
Fatty Acid Metabolism involves cellular biotransforming chemical modifications of fatty acids by enzymatic activity.
Any fluoropyrimidine-based agent with potential antineoplastic activity. As an antimetabolite, a fluoropyrimidine interferes with pyrimidine utilization and incorporation into DNA and RNA.
The release of GLUCOSE from GLYCOGEN by GLYCOGEN PHOSPHORYLASE (phosphorolysis). The released glucose-1-phosphate is then converted to GLUCOSE-6-PHOSPHATE by PHOSPHOGLUCOMUTASE before entering GLYCOLYSIS. Glycogenolysis is stimulated by GLUCAGON or EPINEPHRINE via the activation of PHOSPHORYLASE KINASE.
N-glycans or asparagine-linked glycans are major constituents of glycoproteins in eukaryotes. N-glycans are covalently attached to asparagine with the consensus sequence of Asn-X-Ser/Thr by an N-glycosidic bond, GlcNAc b1-Asn. Biosynthesis of N-glycans begins on the cytoplasmic face of the ER membrane with the transferase reaction of UDP-GlcNAc and the lipid-like precursor P-Dol (dolichol phosphate) to generate GlcNAc a1-PP-Dol. After sequential addition of monosaccharides by ALG glycosyltransferases, the N-glycan precursor is attached by the OST (oligosaccharyltransferase) complex to the polypeptide chain that is being synthesized and translocated through the ER membrane. The protein-bound N-glycan precursor is subsequently trimmed, extended, and modified in the ER and Golgi by a complex series of reactions catalyzed by membrane-bound glycosidases and glycosyltransferases. N-glycans thus synthesized are classified into three types: high-mannose type, complex type, and hybrid type. Defects in N-glycan biosynthesis lead to a variety of human diseases known as congenital disorders of glycosylation.
The efforts by the host to reject a tumor, and the mechanisms by a tumor to evade recognition by the immune system.
An acute infectious process that affects the brain tissue. It is usually caused by viruses and less often by bacteria, parasites, and fungi.
extravasation of blood localized within the cranial vault frequently induced by penetrating and nonpenetrating traumatic injuries.
The production of fat, either fatty degeneration or fatty infiltration; also applied to the normal deposition of fat or to the conversion of carbohydrate or protein to fat.
new abnormal lymph node tissue that grows by excessive cellular division and proliferation more rapidly than normal and continues to grow after the stimuli that initiated the new growth cease.
The science of simulating the motions of a system of particles. (Karplus and Petsko)
agent exciting muscle to functional activity by causing tension on muscle fiber through the nervous tissue.
An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).
invasion and growth of microorganisms in the nervous system; may be clinically inapparent or result in local cellular injury.
sum of chemical changes that occur within the tissues of an organism consisting of anabolism (biosynthesis) and catabolism of nitrogen; the buildup and breakdown of nitrogen for utilization by the organism.
Biosynthesis and catabolism of nucleic acids and their subunits
Hyperplasia of the islets of Langerhans, i.e., of the regions of the pancreas that contain its endocrine cells.
Potassium ion requiring one electron to return to its elemental state.
Protein synthesis is the group of processes that are involved in generation of mature protein molecules. Although protein synthesis may involve translation alone in many cases, in others, it involves also protein folding, integration of prosthetic groups, glycosylation, methylation, phosphorylation, lipidation and any other process that may be involved in maturation of the polypeptide to the biologically active form.
The normal ""downside"" of protein steady state metabolism in cells, involving conjugation, transport, oxidation, and proteolysis; not to be confuse with proteolysis, which applies only to peptide bond hydrolysis.
Biosynthesis and catabolism of proteins and their subunits
condition in which there is a deviation or interruption in the processing of proteins in the body: synthesis, absorption, transport, storage, and utilization.
Protein Cleavage involves hydrolysis by proteolytic enzymes of specific peptide bond(s), forming smaller polypeptides in the target protein during maturation or modification of functional activity.
a rare and often fatal acute, febrile, purulent inflammation of the brain and meninges caused by certain usually free-living soil and water amebas.
Receptor Binding involves a temporary non-covalent, typically highly specific and high affinity, interaction through intermolecular physical forces of attraction and spatial complementarity with a diverse group of intrinsic membrane or cytoplasmic proteins that mediate the biological effects of secreted regulatory signaling molecules through modification of the activity of signal transduction pathways.
A viral vaccine that prevents against rotavirus infection, the leading cause of severe acute gastroenteritis.
Vaccines or candidate vaccines used to prevent infection with SALMONELLA. This includes vaccines used to prevent TYPHOID FEVER or PARATYPHOID FEVER; (TYPHOID-PARATYPHOID VACCINES), and vaccines used to prevent nontyphoid salmonellosis.
Vaccines or candidate vaccines used to prevent bacillary dysentery (DYSENTERY, BACILLARY) caused by species of SHIGELLA.
Steroid Metabolism consists of diverse biochemical reactions that convert steroid compounds, lipids containing a hydrogenated cyclopentanoperhydrophenanthrene ring system, to metabolic derivatives for assorted uses, such as steroid hormone production and biosynthesis of cell membrane constituents.
condition in which there is a deviation from or interruption of the normal structure or function of the white matter of the telencephalon, occurring most frequently in infants and children.
Studies of the role of viruses as factors or cofactors in the etiology of human and animal cancer.
A rating of a body of water based on measurable physical, chemical, and biological characteristics.
Abnormally low glucose concentration in the cerebrospinal fluid.
Diffuse unlocalised atrophy affecting the cerebrum.
Any substance that inhibits topoisomerase, an enzyme that cleaves the DNA backbone to relieve torsional stress in a DNA molecule generated during replication, transcription, and other structural transformations. Inhibition of topoisomerase causes DNA damage, inhibition of DNA replication, and apoptosis.
persistently high arterial blood pressure occurring in or affecting more members of a family than would be expected by chance.
Covalent attachment of PALMITIC ACIDS to other compounds and PROTEINS.
A hereditary disorder that affects the sensory and/or motor nerves or the autonomic nerves.
A serious metabolic condition caused by mutations in the MTHFR gene, medications, or nutritional deficiency. It results in increased levels of homocysteine in the blood. Patients with this condition are at an increased risk for recurrent blood clots formation and cardiovascular accidents.
The causation (or induction), development, and progression of a leukaemic disease.
Anabolic and catabolic biochemical changes to lipids within a cell as materials needed for important life processes.
A malignant mesenchymal neoplasm that arises from the lung. Representative examples include Kaposi sarcoma, leiomyosarcoma, and synovial sarcoma.
A neoplasm composed of a lymphocytic cell population which is usually malignant (clonal) by molecular genetic and/or immunophenotypic analysis. Lymphocytic neoplasms include Hodgkin and non-Hodgkin lymphomas, acute and chronic lymphocytic leukemias, and plasma cell neoplasms.
Removal of one or more methyl groups from a chemical compound.
The first stage of tumor induction by a carcinogen, consisting of subtle alteration of cells by exposure to a carcinogenic agent so that they are likely to form a tumor upon subsequent exposure to a promoting agent. (NCI)
Gyrate atrophy of the choroid and retina due to deficiency of ornithine aminotransferase is clinically characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. Characteristic chorioretinal atrophy with progressive constriction of the visual fields leads to blindness at the latest during the sixth decade of life. Patients generally have normal intelligence (summary by Peltola et al., 2002). See 238970 for another hyperornithinemia syndrome.
A metabolic process in which carbon (usually derived from carbon dioxide) is incorporated into organic compounds (usually carbohydrates). [GOC:jl, GOC:mah]
A relatively common point mutation in which a purine is exchanged for a nonidentical purine or a pyrimidine is exchanged for a nonidentical pyrimidine. Base mispairing and mutagenic chemicals including nitrous acid and 5-bromo-2-deoxyuridine can result in transitions.
A relatively less common point mutation in which a purine is exchanged for a pyrimidine or a pyrimidine is exchanged for a purine.
5-membered aromatic ring structure with a sulfur heteroatom.
Agents used to treat RETROVIRIDAE INFECTIONS.
A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma.
A vaccine based on a synthetic peptide or peptides produced from tissue samples or recombinant sources. Vaccination with peptide vaccines may elicit host immune responses against antigen-expressing cells.
An infectious process affecting the urinary bladder.
A phyllodes tumor with sarcomatous stroma. The sarcomatous component is usually of the fibrosarcomatous type. Liposarcomatous, chondrosarcomatous, osteosarcomatous, or rhabdomyosarcomatous differentiation may also occur in the stroma. It may recur and metastasize following surgical resection. The lung and skeleton are the anatomic sites most frequently involved by metastases.
A carcinoma of the ureter. The majority of ureter carcinomas are transitional cell and less frequently squamous cell carcinomas or adenocarcinomas. --2003
The hydrochloride salt form of nalbuphine, a synthetic phenanthrene opioid with opiate agonist and antagonist effects, used to treat moderate to severe pain and provide preoperative and postoperative analgesia and sedation. Nalbuphine hydrochloride binds to kappa-, mu- and delta-opioid receptors but not to sigma-opioid receptors. This opioid exerts its analgesic actions primarily through kappa-opioid-receptor agonism and partially through mu-opioid receptor agonism.
A series of actions or ritualistic behavior that is difficult to suppress and is performed to relieve or prevent anxiety.
The hydrochloride salt form of hydroxyzine, a piperazine histamine H1-receptor antagonist with anti-allergic, antispasmodic, sedative, anti-emetic and anti-anxiety properties. Hydroxyzine hydrochloride blocks the H1 histamine receptor and prevents the symptoms that are caused by histamine activity on capillaries, bronchial smooth muscle, and gastrointestinal smooth muscle, including vasodilatation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastrointestinal smooth muscle. In addition, hydroxyzine hydrochloride crosses the blood-brain barrier and acts on the histamine H1-receptors in the central nervous system. (NCI05)
A benign or malignant neoplasm that arises from the ovary and is composed of granulosa cells, Sertoli cells, Leydig cells, theca cells, and fibroblasts. Representative examples include thecoma, fibroma, Sertoli cell tumor, and granulosa cell tumor.
An electrocardiographic finding of a PR interval of more than 0.20 seconds in adults.
One of the most common malignant tumors afflicting men. The majority of carcinomas arise in the peripheral zone and a minority occur in the central or the transitional zone of the prostate gland. Grossly, prostatic carcinomas appear as ill-defined yellow areas of discoloration in the prostate gland lobes. Adenocarcinomas represent the overwhelming majority of prostatic carcinomas. Prostatic-specific antigen (PSA) serum test is widely used as a screening test for the early detection of prostatic carcinoma. Treatment options include radical prostatectomy, radiation therapy, androgen ablation and cryotherapy. Watchful waiting or surveillance alone is an option for older patients with low-grade or low-stage disease. -- 2002
A sudden, temporary sensation of heat predominantly experienced by some women during MENOPAUSE. (Random House Unabridged Dictionary, 2d ed)
A carcinoid tumor that shows atypical characteristics and has borderline malignant potential.
The hydrochloride salt form of chlorphentermine, a chlorinated analogue of phentermine, a sympathomimetic amine with central nervous system (CNS) stimulating and anorexic activity. Chlorphentermine acts by facilitating the release of catecholamines, especially noradrenaline and dopamine, from nerve terminals in the brain and also inhibits their uptake. The increase in synaptic concentrations of these catecholamines causes behavioral changes including an increase in motor activity, mental alertness and excitement, causes euphoria, and suppresses appetite.
A derivative of ACETIC ACID that contains two CHLORINE atoms attached to its methyl group.
The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.
Cessation of breathing and/or cardiac function.
Any disorder marked by obstruction of conducting airways of the lung. AIRWAY OBSTRUCTION may be acute, chronic, intermittent, or persistent.
The hydrochloride salt of mechlorethamine, a nitrogen mustard and an analogue of sulfur mustard, with antineoplastic and immunosuppressive activities. Mechlorethamine is metabolized to an unstable, highly reactive ethyleniminium intermediate that alkylates DNA, particularly the 7 nitrogen of guanine residues, resulting in DNA base pair mismatching, DNA interstrand crosslinking, the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis. This agent also exhibits lympholytic properties.
A semisynthetic heparin-like glucosaminoglycan. Although its mechanism of action is unknown, pentosan polysulfate may act as a buffer to control cell permeability by preventing irritating solutes from reaching cells coated with it. Administered orally, excreted pentosan polysulfate adheres to the urinary bladder wall, preventing irritants from entering bladder cells and the development or progression of interstitial cystitis (IC), a complication of some chemotherapies. This agent also exhibits anticoagulant and fibrinolytic properties. (NCI04)
A granuloma located at the root apex of a tooth.
A localized aggressive periodontitis, formerly called localized juvenile periodontitis. It is a destructive form of periodontitis characterized by ALVEOLAR BONE LOSS of the MOLARS and INCISORS.
The hydrochloride salt form of procainamide, an amide derivative exhibiting class 1A antiarrhythmic property and analog of procaine. Procainamide hydrochloride reversibly binds to and blocks activated (open) voltage-gated sodium channels, thereby blocks the influx of sodium ions into the cell, which leads to an increase in threshold for excitation and inhibit depolarization during phase 0 of the action potential. In addition, the effective refractory period (ERP), action potential duration (APD), and ERP/APD ratios are increased, resulting in decreased impulse conduction velocity. The lasting action potential may also be due to blockage of outward K+ currents. The result is a decrease in automaticity, increase in refractory period and slowing of impulse conduction.
A rare acute life-threatening systemic bacterial noncontagious illness caused by any of several related staphylococcal exotoxins. It is characterized by high fever, hypotension, rash, multi-organ dysfunction, and cutaneous desquamation during the early convalescent period. The toxins affect the host immune system, causing an exuberant and pathological host inflammatory response. Laboratory findings include leukocytosis, elevated prothrombin time, hypoalbuminemia, hypocalcemia, and pyuria.
The major active component of silymarin flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum; it is used in the treatment of HEPATITIS; LIVER CIRRHOSIS; and CHEMICAL AND DRUG INDUCED LIVER INJURY, and has antineoplastic activity; silybins A and B are diastereomers.
parasympathomimetic cholinergic agonist with predominantly muscarinic effects.
A psychologically and socially impaired state, with or without physiological changes, that develops as a result of using cocaine and which leads to compulsive behaviors to acquire the substance.
A hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). The activated form of Factor V (Factor Va) is more slowly degraded by activated protein C. Factor V Leiden mutation (R506Q) is the most common cause of APC resistance.
The paired nucleotides in a DNA or RNA sequence.
A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)
A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.
The joining of RNA from two different genes. One type of trans-splicing is the ""spliced leader"" type (primarily found in protozoans such as trypanosomes and in lower invertebrates such as nematodes) which results in the addition of a capped, noncoding, spliced leader sequence to the 5' end of mRNAs. Another type of trans-splicing is the ""discontinuous group II introns"" type (found in plant/algal chloroplasts and plant mitochondria) which results in the joining of two independently transcribed coding sequences. Both are mechanistically similar to conventional nuclear pre-mRNA cis-splicing. Mammalian cells are also capable of trans-splicing.
A syndrome characterized by the clinical triad of advanced chronic liver disease, pulmonary vascular dilatations, and reduced arterial oxygenation (HYPOXEMIA) in the absence of intrinsic cardiopulmonary disease. This syndrome is common in the patients with LIVER CIRRHOSIS or portal hypertension (HYPERTENSION, PORTAL).
A woman who currently is pregnant or has been in the past, irrespective of the pregnancy outcome.
A bipyridine agent with positive inotropic and vasodilator properties. Milrinone lactate selectively inhibits fraction III cyclic adenosine monophosphate (cAMP) phosphodiesterase isozymes in the heart and vascular muscles, thereby increasing cAMP and, consequently, an increase in cAMP-dependent intracellular ionized calcium and myocardium contractile force, and vasodilation in arteriolar and venous vascular smooth muscle. This agent improves hemodynamics in patients with ventricular dysfunction by increasing the stroke volume index and left ventricular contractility and by producing pulmonary vasodilation. (NCI04)
An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic.
The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).
Pathological processes involving the integrity of blood circulation. Hemostasis depends on the integrity of BLOOD VESSELS, blood fluidity, and BLOOD COAGULATION. Majority of the hemostatic disorders are caused by disruption of the normal interaction between the VASCULAR ENDOTHELIUM, the plasma proteins (including BLOOD COAGULATION FACTORS), and PLATELETS.
Hemorrhagic and thrombotic disorders resulting from abnormalities or deficiencies of coagulation proteins.
The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.
A pathological process consisting of the formation of new blood vessels in the CHOROID.
The hydrochloride salt of sertraline, a synthetic derivative of naphthalenamine with anti-serotoninergic and anti-depressant properties. Sertraline appears to selectively inhibit the neuronal uptake of serotonin, raising serotonin levels in the CNS.
An isoquinoline antiviral agent with activity against myxoviruses and paramyxoviruses.
Methylprednisolone derivative that is used as an anti-inflammatory agent for the treatment of ALLERGY and ALLERGIC RHINITIS; ASTHMA; and BURSITIS; and for the treatment of ADRENAL INSUFFICIENCY.
An orally bioavailable, non-steroidal selective androgen receptor modulator (SARM), with potential tissue-selective androgenic/anti-androgenic activities. Upon oral administration, SARM RAD140 acts as an agonist in select tissues, such as skeletal muscle and bone, where it binds to and activates androgen receptors (ARs). In the prostate and breasts, RAD140 acts as an antagonist and blocks AR activation and AR-mediated cellular proliferation. Therefore, this agent may improve bone formation and muscle mass and strength, and may inhibit both the growth of the prostate in males and AR-dependent breast cancer cell proliferation. Compared to anabolic agents, SARMs have reduced androgenic properties.
A bismuth derivative of tetrabromopyrocatechol used as a topical ointment for the treatment of blepharitis.
A thiosemicarbazone derivative with activity against variola virus.
An antibiotic agent with activity against drug-resistant strains of cholera bacteria.
An sulfonylurea with structural variation to glibenclamide, in which 2-methoxy-5-chlorobenzyl is replaced by a cyclic acyl group, with hypoglycemic activity. Glicaramide also exerts peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic activity.
A benzothiadiazinesulfonamide derivative belonging to the class of the thiazide diuretics.
An imidazolidinone-based aldosterone antagonist with potassium-sparing diuretic activity. Azolimine antagonizes aldosterone at the mineralocorticoid receptor in the kidneys, thereby increasing sodium excretion and inhibiting potassium excretion.
A water-soluble amphipathic formulation of d-alpha-tocopherol succinate coupled, through a succinate linker, to polyethylene glycol (PEG) 1000. Due to its amphipathic property in which it forms its own micelles, tocophersolan is easily taken up into enterocytes, even in the absence of bile salts; fat soluble d-alpha-tocopherol is then released after hydrolysis. This formulation enhances the absorption of d-alpha-tocopherol compared to the administration of free d-alpha-tocopherol. In addition, tocophersolan may enhance the absorption of water-insoluble agents and other fat-soluble vitamins.
The terephthalate salt of oxycodone, a methylether of oxymorphone and semisynthetic, agonistic opioid with analgesic and antitussic properties. Oxycodone terephthalate exerts its analgesic actions by binding to the mu-receptors in the central nervous system (CNS), thereby mimicking the effects of endogenous opiates. By binding to the mu-opioid receptors, oxycodone terephthalate also causes euphoria, anxiolysis, miosis, sedation, physical dependence, constipation, respiratory depression as well as a depressive effect on the cough center in the medulla.
A second-generation sulfonylurea with antihyperglycemic activity. Compared to first-generation compounds and like other second-generation compounds, glyclopyramide works more effectively with fewer side effects. This agent has a relatively short half-life of 4.0 hours and is excreted mainly by the kidneys.
An organic salt containing a one to one ratio of methenamine, a heterocyclic organic compound, and mandelic acid, an aromatic alpha hydroxy acid, used in the treatment of urinary tract infections.
An aziridine alkylating agent that cross-links with DNA, causing inhibition of DNA synthesis. It was studied for use in colon cancer. (NCI)
An azirine-based thiotepa derivative with alkylating activity. Azetepa is able to alkylate and crosslink DNA, causing DNA damages and eventually an inhibition of cellular proliferation.
The acetate salt of a synthetic fluorinated corticosteroid with antiinflammatory and antiallergic activities. As a glucocorticoid-receptor agonist, fludrocortisone binds to cytoplasmic receptors, translocates to the nucleus, and subsequently initiates the transcription of glucocorticoid-responsive genes such as lipocortins to inhibit phospholipase A2 (PLA2). Inhibition of PLA2 activity prevents the release of arachidonic acid, a precursor of eicosanoids such as prostaglandins and leukotrienes; eicosanoids are important mediators in the pro-inflammatory response mechanism. As a mineralocorticoid-receptor agonist, this agent stimulates Na+ reabsorption and water retention and K+ and H+ secretion in the distal tubules and collecting ducts of the kidney.
An acid azo dye commonly used as a stain to distinguish viable from non-viable cells. It was previously used to treat trypanosomiasis.
The pivoxil prodrug form of sulbactam, a semi-synthetic beta-lactamase inhibitor, with beta-lactam antibiotic adjuvant activity. After oral administration of sulbactam pivoxil, the ester bond is cleaved, releasing active sulbactam. The beta-lactam ring of sulbactam irreversibly binds to beta-lactamase at or near its active site, thereby blocking enzyme activity and preventing metabolism of other beta-lactam antibiotics by the enzyme.
A topical local anesthetic preparation that is composed of a mixture of lidocaine and prilocaine. It is used to provide anesthesia during minor surgery and for the treatment of PREMATURE EJACULATION.
A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.
A fibrate derivative with antilipidemic activity. Unlike clofibrate, dulofibrate is selective for a reduction in triglycerides.
Beta-defensin 1 (68 aa, ~7 kDa) is encoded by the human DEFB1 gene. This protein is involved in chemotaxis and has bactericidal activity.
A furochromone with antihyperlipidemic activity. In an animal model, khelloside lowered low density lipoprotein cholesterol, high density lipoprotein cholesterol, and total cholesterol; very low density lipoprotein cholesterol and triglycerides were not changed.
A synthetic alkyl derivative prodrug of the antineoplastic agent 6-mercaptopurine (6-MP). In vivo, 9-ethyl 6-mercaptopurine appears to be converted to 6-MP, which substitutes for the normal nucleoside and fraudulently incorporates into DNA and inhibits de novo purine synthesis, thereby inducing cell death. (NCI04)
A quassinoid phytochemical isolated from Simaba cedron and other plant species with potential antineoplastic activity. Chaparrin is a mixture of compounds that includes flavonoids, antioxidants, and nordihydroguaiaretic acid (NDGA). NDGA is an antioxidant and lipoxygenase inhibitor that promotes cell differentiation, induces G1 phase cell-cycle arrest, and causes apoptosis in certain cancer cell lines. (NCI04)
A family of ubiquitously-expressed peroxidases that play a role in the reduction of a broad spectrum of PEROXIDES like HYDROGEN PEROXIDE; LIPID PEROXIDES and peroxinitrite. They are found in a wide range of organisms, such as BACTERIA; PLANTS; and MAMMALS. The enzyme requires the presence of a thiol-containing intermediate such as THIOREDOXIN as a reducing cofactor.
A broad spectrum protein tyrosine kinase inhibitor that inhibits epidermal growth factor receptor, GTPase activity of transducin, aldosterone secretion in response to Angiotensin II, and suppresses the activation of MAP kinases. (NCI)
A lipophilic disaccharide tripeptide derivative of muramyl dipeptide (MDP) with immunomodulatory activity. Disaccharide tripeptide glycerol dipalmitoyl (DTP-GDP)stimulates macrophage activity and increases serum levels of tumor necrosis factor alpha (TNF alpha), neopterin, interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8, and IL-12, which may activate host immune system antitumor functions. DTP-GDP may be packaged in liposomes for improved delivery. The immunomodulatory effects of this agent may be superior to those of MDP.
A compound that inhibits the Protein-Tyrosine Kinase Activity of p56lck.
An angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Temocaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Temocaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A glucopyranoside and inhibitor of alpha-glucosidase with antihyperglycemic activity. Camiglibose binds to and inhibits alpha-glucosidase, an enteric enzyme found in the brush border of the small intestines that hydrolyzes oligosaccharides and disaccharides into glucose and other monosaccharides. This prevents the breakdown of larger carbohydrates into glucose and decreases the rise in postprandial blood glucose levels.
A quassinoid glycoside phytochemical isolated from the plant Picrasma ailanthoides with potential antineoplastic activity. (NCI04)
A carbamate-derived reversible CHOLINESTERASE INHIBITOR that is selective for the CENTRAL NERVOUS SYSTEM and is used for the treatment of DEMENTIA in ALZHEIMER DISEASE and PARKINSON DISEASE.
A third-generation DNA repair inhibitor that modulates multi-drug resistance.
A nucleoside reverse transcriptase inhibitor analog of adenosine. Lodenosine is a synthetic purine fluoro-dideoxyadenosine derivative that was rationally designed to have improved chemical and enzymatic stability. It has shown activity against clinical isolates and cell lines that are resistant to AZT, dideoxyinosine, and dideoxycytosine.
A synthetic tetra-methylated derivative of nordihydroguaiaretic acid (NDGA) and transcriptional inhibitor with potential antiviral, antiangiogenic, and antineoplastic activities. Terameprocol competes with the transcription factor Sp1 for specific Sp1 DNA binding domains within gene promoter regions during DNA synthesis. In virally-infected cells, blocking of the Sp1 binding site suppresses Sp1-regulated viral promoter activity and gene expression, thereby inhibiting viral transcription and replication. In tumor cells, blockage of Sp1 binding sites by this agent interferes with the transcription of the Sp1-dependant genes cyclin-dependant kinase (Cdc2), survivin, and vascular endothelial growth factor (VEGF), which are overexpressed in a variety of cancers. By suppressing Sp1-regulated transcription of these genes, terameprocol may reduce tumor angiogenesis and tumor cell proliferation and induce tumor cell apoptosis.
A fusion protein consisting of the Fv portion of a monoclonal antibody attached to a 38-kDa fragment of the Pseudomonas exotoxin A (with amino acids 365-380 deleted). LMB-2 immunotoxin targets the interleukin 2 receptor (also known as IL-2R or CD25) which is expressed on activated normal T and B cells and macrophages and on the cells of various hematologic malignancies. The antibody attaches to the IL-2R on the cell membrane, facilitating the entry of the exotoxin. The exotoxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis. (NCI04)
Cancell (Entelev or Cantron), is a liquid that has been produced in various forms, principally by two manufacturers, since the late 1930s. The exact composition of Cancell/Entelev is unknown, but the U.S. Food and Drug Administration (FDA) has listed the components as inositol, nitric acid, sodium sulfite, potassium hydroxide, sulfuric acid, and catechol. NCI studies determined that the mixture lacked substantial antitumor activity. (from CancerNet)
A 3-isobutyl derivative of gamma-amino butyric acid (GABA) with anti-convulsant, anti-epileptic, anxiolytic, and analgesic activities. Although the exact mechanism of action is unknown, pregabalin selectively binds to alpha2delta (A2D) subunits of presynaptic voltage-dependent calcium channels (VDCCs) located in the central nervous system (CNS). Binding of pregabalin to VDCC A2D subunits prevents calcium influx and the subsequent calcium-dependent release of various neurotransmitters, including glutamate, norepinephrine, serotonin, dopamine, and substance P, from the presynaptic nerve terminals of hyperexcited neurons; synaptic transmission is inhibited and neuronal excitability is diminished. Pregabalin does not bind directly to GABA-A or GABA-B receptors and does not alter GABA uptake or degradation.
A peptide agonist of the gonadotropin releasing hormone-1 receptor (GnRH-1R) that is conjugated to the anthracycline antibiotic doxorubicin with potential antineoplastic activity. Zoptarelin doxorubicin binds to GnRH-1Rs, which may be highly expressed on endometrial and ovarian tumor cell membrane surfaces, and is internalized. Once inside the cell, the doxorubicin moiety of this agent intercalates into DNA and inhibits the topoisomerase II activity, which may result in the inhibition of tumor cell DNA replication and tumor cell proliferation.
A bicyclam with hematopoietic stem cell-mobilizing properties. AMD3100 blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell (HSC) release from bone marrow and HSC movement into the peripheral circulation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=410786&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=410786&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1777"" NCI Thesaurus)
A member of the tyrphostin family of tyrosine kinase inhibitors that inhibits epidermal growth factor receptor, blocks leukemic cell growth in vitro and in vivo by inducing programmed cell death. Inhibits the constitutive activation of STAT-3 DNA binding and IL-2-induced growth of Mycosis fungoides tumor cells. (NCI)
A recombinant monoclonal antibody interleukin-2 receptor antagonist. Daclizumab binds specifically to the alpha subunit of the human interleukin-2 (IL-2) receptor expressed on the surface of activated lymphocytes in vivo, thereby inhibiting IL-2 binding and IL-2-mediated lymphocyte activation, a critical cellular immune response pathway.
A synthetic oxazolidinone derivative, Linezolid selectively inhibits an early step in bacterial protein synthesis and affects blood pressure through monoamine oxidase inhibition. It is effective against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus strains, coagulase-negative Staphylococci, vancomycin-resistant Enterococci, and penicillin-resistant Streptococcus pneumoniae strains. (NCI04)
A member of the tyrphostin family of tyrosine kinase inhibitors, that selectively inhibits epidermal growth factor receptor kinase activity. (NCI)
An agent that inhibits the transformation of 7-dehydrocholesterol to cholesterol and also inhibits sterol absorption.
A long-acting, first-generation, cyclohexyl sulfonylurea with antihyperglycemic activity. Metahexamide has greater potency than chlorpropamide and tolbutamide. This agent may cause jaundice.
A vasopeptidase inhibitor with antihypertensive activity. Omapatrilat exerts its effect by inhibiting angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP). ACE inhibition results in inhibition of the renin-angiotensin-aldosterone system thereby leading to the reduction of vasoconstriction. Inhibition of NEP leads to the inhibition of hydrolyzation of a number of endogenous vasoactive peptides, such as bradykinin and substance P and as NEP is the principal enzyme degrading natriuretic peptides, NEP inhibition also results in an increase in natriuretic peptidase circulation. Ultimately both effects result in blood vessel relaxation.
A nucleoside reverse transcriptase inhibitor analog of guanosine. This agent decreases HIV viral loads, retards or prevents the damage to the immune system, and reduces the risk of developing AIDS.
A non-peptidomimetic agent that inhibits both wild type and drug resistant forms of human immunodeficiency virus (HIV) protease.
An alkyl sulfonate with potential antineoplastic activity. Piposulfan alkylates DNA, thereby producing DNA interstrand crosslinks and DNA strand breaks and inhibiting DNA replication. This agent has been shown to exhibit antitumor activity in an animal model of prostate cancer. (NCI04)
A murine monoclonal antibody that attaches to the tumor-associated antigen CA125. Vaccination with monoclonal antibody B43.13 may stimulate a host cytotoxic immune response against tumor cells that express CA125. (NCI04)
A member of the tyrphostin family of tyrosine kinase inhibitors that inhibits epidermal growth factor receptor. (NCI)
A protein isolated from the cyanobacterium Nostoc ellipsosporum with activity against human immunodeficiency virus (HIV). Cyanovirin-N binds to the sugar moieties on the HIV particle and impairs the binding of virion-associated gp120 to cell-associated CD4 on mucosal surfaces and impedes membrane fusion.
A radioconjugate composed of the positron-emitting radioisotope fluorine F 18 labeled benzylguanidine, a synthetic analogue of the adrenergic neurotransmitter norepinephrine (NE), with potential use in the diagnostic imaging of human norepinephrine transporter (hNET)-expressing cells by either positron emitting tomography (PET) or computed tomography (CT). Upon administration, meta-fluorine F 18 fluorobenzylguanidine (MFBG) is taken up by and accumulates in both the granules of adrenal medullary chromaffin cells and the pre-synaptic granules of adrenergic neurons in a manner almost identical to that of NE. In turn, hNET-expressing tumor cells can be imaged by PET or CT. hNET, a transmembrane protein and regulator of catecholamine uptake normally restricted to the central and peripheral sympathetic nervous system, is overexpressed in certain tumor cell types.
A quinazoline derivative that selectively inhibits EGFR kinase activity and suppresses the growth of psoriatic keratinocytes.
A synthetic phosphorothioate oligodeoxynucleotide. As an antisense molecule, ISIS 3521 hybridizes to the 3-untranslated region of the human protein kinase C (PKC-alpha) mRNA, thereby inhibiting PKC-alpha expression and growth of PKC-alpha-dependent tumor cells. (NCI04)
A chimeric monoclonal antibody to TNF-ALPHA that is used in the treatment of RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; PSORIATIC ARTHRITIS and CROHN'S DISEASE.
A 20-mer mixed backbone oligonucleotide exhibiting anti-viral activity. GEM-132 is comprised of a strand of synthetic DNA with a modified RNA at each end (2-O-methylribonucleosides at the two 3- and four 5-terminal nucleotides) which is complementary to the intron-exon boundary of the UL35 and UL37 pre-mRNA transcripts of human cytomegalovirus. (NCI)
A recombinant form of neurotrophic growth factor that regulates the development and maintenance of motor neurons expressing trk B receptor tyrosine kinase, with potential use in neurodegenerative disorders. (NCI)
An isothiazole derivative of 5-amino-3-methylisothiazolocarboxylic acid I with antiviral activity against human herpes simplex viruse types 1 and 2, and varicella zoster virus.
A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.
A dialkyl ether dicarboxylic acid with antihyperlipidemic activity. In animal models gemcabene increased high density lipoprotein (HDL) cholesterol levels and increased HDL particle size. Low-density lipoprotein cholesterol, trigylcerides, and apolipoprotein C-III levels were decreased as well. In human test subjects, the HDL lowering effect of gemcabene was only seen in patients with high (>200 mg/dl) levels of triglycerides.
A humanized monoclonal antibody against the fusion protein (F protein) of human respiratory syncytial virus (RSV), with prophylactic application in respiratory syncytial virus infections. RSV F protein, a small envelop glycoprotein, is not only required for cytopathic syncytia resulting from cell-to-cell fusion, but is also necessary for viral spreading and evading neutralizing antibody. Palivizumab neutralizes and inhibits fusion activity of RSV, thereby preventing syncytia formation. Administration of this antibody does not interfere with other immunizations.
A bi-fluorinated derivative of the semi-synthetic vinca alkaloid vinorelbine with antitubulin, antineoplastic, and antiangiogenic activities. Vinflunine inhibits tubulin assembly without any stablization of assembled microtubules at concentrations comparable to those of other vinca alkaloids such as vincristine, vinblastine and vinorelbine; this effect on microtubule dynamics results in cell cycle arrest in mitosis and apoptosis. Compared to other vinca alkaloids, this agent binds weakly to the vinca-binding site, indicating that vinflunine may exhibit reduced neurotoxicity.
A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.
A hybrid polar compound that induces terminal differentiation and/or apoptosis in various transformed cells. It is an inhibitor of histone deacetylase.
A naturally occurring short-chain fatty acid, and immediate precursor of gamma amino butyric acid (GABA) with neuromodulatory and anesthetic properties. 4-Hydroxybutyric Acid (GHB) is found in all human tissues, with the highest concentration in the brain. This agent stimulates the GHB receptor, and to a lesser extent GABA-B receptors. Although, the precise function and metabolic pathways of GHB are not fully understood, this agent easily crosses the blood-brain barrier, and affects the activities and levels of dopamine, acetylcholine, dynorphin and serotonin. The primary effect of GHB is central nervous system depression, thereby, its main usage is to induce anesthesia.
A reversible metabolite of taurolidine and an amino acid taurine derivative, with antibacterial and antineoplastic activity. Taurultam, like its congener taurolidine, inhibits proliferation of microvascular endothelial cells, although to a lesser extent, by selectively inhibiting the adhesion of endothelial cells to laminin but not to collagen I and fibronectin.
An herbal formula containing burdock root (Arctium lappa), Turkey rhubarb root (Rheum palmatum), sheep sorrel (Rumex acetosella), and slippery elm bark (Ulmus fulva) with potential immunostimulating, anti-inflammatory and anti-tumor activities. The extract's chemical profile, their respective concentrations and the mechanism of action of Essiac are largely unknown due to the proprietary nature of the formula and product inconsistency. Several chemical classes in Essiac are consistently represented and may attribute to its therapeutic effect, including anthraquinone derivatives such as rhein and emodin, high molecular polysaccharides, and lignans such as arctigenin. However, all these chemicals are unlikely to occur in high concentrations in Essiac, and its potential therapeutic effect may be attributed to a potential synergistic effect of these various compounds.
A sulfonamide and carbonic anhydrase inhibitor with specific affinity for carbonic anhydrase II. Following topical ocular administration, brinzolamide inhibits carbonic anhydrase II, an enzyme that is responsible for the movement of sodium and fluid transport in the eye. This inhibition leads to a decrease in aqueous humor secretion, probably by slowing the formation of bicarbonate ions, and results in a reduction in intraocular pressure. Brinzolamide is used to treat increased pressure in the eye caused by open-angle glaucoma.
A synthetic non-nucleoside reverse transcriptase (RT) inhibitor with antiviral activity. Efavirenz binds directly to the human immunodeficiency virus type 1 (HIV-1) RT, an RNA-dependent DNA polymerase, blocking its function in viral DNA replication. In combination with other antiretroviral drugs, this agent has been shown to significantly reduce HIV viral load, retarding or preventing damage to the immune system and reducing the risk of developing AIDS. Efavirenz induces activity of the cytochrome P450 system, accelerating its own metabolism.
A peptidomimetic HIV protease inhibitor that retains activity against HIV protease with the Val 82 mutation. Lopinavir is less affected by binding to serum proteins than the structurally-related drug ritonavir.
A cancer vaccine adjuvant consisting of a combination of the active monophosphoryl lipid A component of lipopolysaccharide (LPS) isolated from the bacterium Salmonella minnesota combined with a residue of the cell wall of the bacterium Mycobacterium phlei. Detox is a non-specific immunostimulant that may enhance the host immune response to certain cancer vaccines. (NCI04)
Density-regulated protein (198 aa, ~22 kDa) is encoded by the human DENR gene. This protein plays a role in the regulation of translation.
A retinobenzoic acid with potential antineoplastic activity. TAC-101 inhibits retinoblastoma-gene product (RB) phosphorylation and increases the presence of 2 cyclin-dependent kinase (CDK) inhibitors, resulting in cell cycle arrest. This agent also causes a cytotoxic decline in cyclin A and thymidylate synthase expression. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=350384&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=350384&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C38684"" NCI Thesaurus)
A substance being studied in the treatment of some types of leukemia and lymphoma. It is a type of purine nucleoside phosphorylase (PNP) inhibitor.
A chimeric murine-human monoclonal antibody that functions as an INTERLEUKIN 2 RECEPTOR antagonist by binding to the alpha chain (CD25 ANTIGEN) of the interleukin-2 receptor on the surface of activated T-LYMPHOCYTES. It is used in the prevention of acute graft rejection episodes in patients undergoing renal transplantation.
A neoplasm which, on morphologic grounds, can not be classified with certainty as benign or malignant.
A carcinoma arising from the vulva. It usually affects elderly women but has been observed in premenopausal women as well. The most frequently seen histologic type is squamous cell carcinoma. The most common site of involvement is the labia majora. In many cases, the development of vulvar cancer is preceded by condyloma or squamous dysplasia.
Inspiratory stridor is a high pitched sound upon inspiration that is generally related to laryngeal abnormalities.
Hashimoto thyroiditis is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. Hashimoto thyroiditis is a form of chronic inflammation that can damage the thyroid, reducing its ability to produce hormones.One of the first signs of Hashimoto thyroiditis is an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing. As damage to the thyroid continues, the gland can shrink over a period of years and the goiter may eventually disappear.Other signs and symptoms resulting from an underactive thyroid can include excessive tiredness (fatigue), weight gain or difficulty losing weight, hair that is thin and dry, a slow heart rate, joint or muscle pain, and constipation. People with this condition may also have a pale, puffy face and feel cold even when others around them are warm. Affected women can have heavy or irregular menstrual periods and difficulty conceiving a child (impaired fertility). Difficulty concentrating and depression can also be signs of a shortage of thyroid hormones.Hashimoto thyroiditis usually appears in mid-adulthood, although it can occur earlier or later in life. Its signs and symptoms tend to develop gradually over months or years.
A hemangioma arising from the fetal blood vessels in the placental villi.
Drusen (singular, 'druse') are tiny yellow or white accumulations of extracellular material (lipofuscin) that build up in Bruch's membrane of the eye. This class refers to the presence of Drusen in the macula.
A perceived issue with a person's emotional wellbeing.
A dietary protein isolated from soybeans that contains isoflavone phytoestrogens. Soy protein isolate has been shown to reduce tumor incidence and growth in some animal studies, possibly by modulating estrogen metabolism, reducing tumor cell proliferation, and inducing tumor cell apoptosis. Soy protein isolate may also inhibit endothelial cell proliferation. Isoflavone phytoestrogens display mild estrogen-like activities which may regulate hormone balance and reduce the risks of breast cancer, heart disease, and osteoporosis. (NCI04)
A quinazoline folate analogue with antineoplastic activity. After transport into cells via the reduced folate carrier, raltitrexed undergoes intracellular polyglutamation and blocks the folate-binding site of thymidylate synthase, thereby inhibiting tetrahydrofolate activity and DNA replication and repair and resulting in cytotoxicity. (NCI04)
An anti-idiotypic (anti-Id) rat monoclonal antibody (MoAb) that mimics the disialoganglioside GD2, a cancer-associated antigen present on melanoma, small cell lung cancer, sarcoma, neuroblastoma, and other malignancies. GD2 is a highly expressed glycosphingolipid by melanoma and other neuroectodermal tumors with only minimal expression on normal tissues. Vaccination with anti-Id A1G4 MoAb may elicit cellular and humoral immune responses against GD2 expression tumor cells.
A cancer vaccine containing a RAS oncogene-encoded peptide with potential antineoplastic activity. RAS peptide cancer vaccine may stimulate a RAS peptide-specific antitumoral T-cell cytotoxic immune response, resulting in an inhibition of tumor cell proliferation and tumor cell death. (NCI04)
A vaccine comprised of autologous dendritic cells pulsed with mRNA-encoded Carcinoembryonic Antigen (CEA) targeting tumor cells expressing CEA. (NCI)
The reemergence of a mantle cell lymphoma after a period of remission.
The reemergence of an aggressive adult non-Hodgkin lymphoma after a period of remission.
An indolent non-Hodgkin lymphoma occurring in adults. Representative examples include small lymphocytic lymphoma, lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia, marginal zone B-cell lymphoma, and grade 1 and 2 follicular lymphoma.
An aggressive non-Hodgkin lymphoma occurring in adults. Representative examples include Burkitt lymphoma, precursor B-lymphoblastic lymphoma, precursor T-lymphoblastic lymphoma, and adult T-cell lymphoma/leukemia.
A vaccine consisting of a replication-defective recombinant canarypox virus (ALVAC) that encodes the gene for human interleukin-12 (hIL-12). Produced mainly by B-cells, IL-12 is an endogenous cytokine that activates natural killer (NK) cells, promotes cytotoxic T lymphocyte (CTL) responses, induces the release of interferon-gamma (IFN-gamma), and may exhibit antitumor and anti-angiogenic effects. Vaccination with canarypox-hIL-12 melanoma vaccine may stimulate the host immune system to mount an immune response against tumor cells, thereby inhibiting tumor growth and/or metastasis. (NCI04)
A whole cell vaccine comprised of irradiated allogenic pancreatic tumor cells transfected with a plasmid DNA encoding human sargramostim (GM-CSF). Vaccination results in expression of GM-CSF, which induces proliferation and differentiation of hematopoietic lineage cells as well as stimulating macrophage and dendritic cell functions in antigen presentation and antitumor cell-mediated immunity. Furthermore, administration of this pancreatic tumor cell vaccine may elicit a cytotoxic T lymphocyte (CTL) response against similar host tumor cells, resulting in decreased tumor growth.
A murine monoclonal anti-idiotype antibody (anti-Id). Anti-Id 11D10 mimics a specific epitope of the high molecular weight human milk fat globule (HMFG) glycoprotein primarily expressed by human breast and some other tumor cells at high density. This specific HMFG epitope is identified by mAb BrE1, which was used as the immunizing antibody, or Ab1 to generate the anti-Id (Ab2) 11D10. Anti-ID 11D10 reacts specifically with breast tumor cells and with minimal reactivity with normal tissues. Vaccination with anti-Id 11D10 induces anti-anti-idiotype antibodies (Ab3) that may react with breast cancer cell lines expressing the HMFG membrane epitope.
An immunotoxin of monoclonal antibody (MoAb) RFB4 covalently linked to two deglycosylated ricin toxin A-chain (Di-dgA). This agent can be extracted from castor beans. MoAb RFB4 recognizes CD22 antigen, a B-cell adhesion protein expressed on malignant cells in about 70 percent of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Ricin toxin A-chain, a potent protein synthesis inhibitor, was deglycosylated and was used in this immunoconjugate to avoid hepatic entrapment. This Di-dgA conjugated MoAb RFB4 delivers 7 fold more cytotoxicity than the single dgA immunotoxin against CD22-positive malignant cells.
A murine IgG1 monoclonal antibody directed against the human transferrin (Tf) receptor. Monoclonal antibody A27.15 binds to the Tf receptor, blocking the binding of transferrin to the receptor and resulting in decreased tumor cell growth. (NCI04)
A murine IgG1 monoclonal antibody directed against the human transferrin (Tf) receptor. Monoclonal antibody E2.3 binds to the Tf receptor, blocking the binding of transferrin to the receptor and resulting in decreased tumor cell growth. (NCI04)
Familial embryonal neoplasm derived from nephrogenic blastemal cells. Several lines of differentiation, including blastemal, stromal and epithelial, are usually expressed. Comprises approximately 1% of Wilms tumors. (AFIP fascicle version 2.0)
A radioimmunoconjugate comprised of the chimeric monoclonal antibody G-250 conjugated with iodine I 131 with potential antineoplastic activity. The antibody moiety of iodine I 131 chimeric monoclonal antibody G-250 binds to G-250, a renal-cell carcinoma-associated antigen, delivering cytotoxic iodine I 131 specifically to renal carcinoma cells that express G-250.
A radioactive chemical being studied to treat bone pain associated with cancer.
A colloidal dispersion formulation of 9-Aminocamptothecin, a water-insoluble camptothecin derivative. Aminocamptothecin binds to the nuclear enzyme topoisomerase I, thereby inhibiting repair of single-strand DNA breakages. Because the terminal lactone ring of aminocamptothecin required for the agent's antitumor activity spontaneously opens under physiological conditions to an inactive carboxy form, the drug must be administered over an extended period of time to achieve effective cytotoxicity.
A bivalent fusion protein consisting of disulfide-stabilized Fv fragments of an anti-HER2 (erbB2) monoclonal antibody (e23) and a truncated version of the M(r) 38 fragment of Pseudomonas exotoxin that lacks the toxin's cell binding domain. ERB-38 immunotoxin binds specifically to cells that overexpress HER2, the antigenic target of the monoclonal antibody; the exotoxin portion of the immunotoxin then lyses the cells bound by the antibody portion. (NCI04)
A recombinant form of the endogenous human keratinocyte growth factor with cell growth promoting activity. Palifermin acts in the manner similar to the endogenous keratinocyte growth factor that binds to keratinocyte growth factor receptors on the epithelial cell surface in the lining of mouth and gastrointestinal tract. This results in stimulation of epithelial cell proliferation, differentiation and upregulation of cytoprotective mechanisms.
A radioconjugate of biotin and yttrium Y 90 (Y-90) linked through the bifunctional macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) with radioimmunotherapy property. Biotin is a water-soluble B-complex vitamin, present in minute amounts in every living cell, while its level in cancerous tissue is higher than that of normal tissue. Y 90-DOTA-Biotin could be used in 3-step pre-targeting radioimmunotherapy that employs a tumor targeting antibody conjugated with streptavidin, the natural ligand of biotin.
A benign or malignant neoplasm that affects the brain stem.
The disappearance of all signs of cancer in response to treatment.
An anticancer drug that interferes with the DNA in cancer cells.
A malignant neoplasm originating from the surface ovarian epithelium.
Cancer that has spread beyond the layer of tissue in which it developed and is growing into surrounding, healthy tissues.
A lymph node in the area of the armpit (axilla) to which cancer has spread. This spread is determined by surgically removing some of the lymph nodes and examining them under a microscope to see whether cancer cells are present.
Cancer that is growing, spreading, or getting worse.
A malignant neoplasm that does not respond to treatment.
A radioactive substance used in the treatment of bone cancer and bone metastases (cancers that have spread from the original tumor to the bone). Samarium 153 is a radioactive form of the element samarium. It collects in bone, where it releases radiation that may kill cancer cells. It is a type of radioisotope.
Cancer that is neither decreasing nor increasing in extent or severity.
Stage Group II is subdivided into IIA and IIB on the basis of whether the primary tumor is T3 or T4, respectively. T3: Tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues. T4: Tumor directly invades other organs or structures, and/or perforates visceral peritoneum. (AJCC 6th ed.) - 2003
Stage Group III is subdivided into IIIA (T1-2, N1, M0), IIIB (T3-4, N1, M0) or IIIC (any T, N2 M0). T1: Tumor invades the submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades through the muscularis propria into the subserosa or into non-peritonealized pericolic or perirectal tissues. T4: Tumor directly invades other organs or structures, and/or perforates visceral peritoneum. N1: Metastasis in 1 to 3 regional lymph nodes N2: Metastasis in 4 or more regional lymph nodes. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage IV includes: Any T, any N, M1. M1: Distant metastasis. (AJCC 6th ed.) - 2003
Ann Arbor Classification: Stage I: Involvement of a single lymph node region (I); or localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE) (rare in Hodgkin lymphoma).- 2003
Ann Arbor Classification: Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II); or localized involvement of a single extralymphatic organ or site in association with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm (IIE). - 2003
A term that refers to the staging of prostate carcinoma according to the Whitmore-Jewett staging system.
A vaccine comprised of CD80-transfected allogenic breast cancer cells to induce T-cell response.
A peptide vaccine containing human mucin 2 (MUC2) protein conjugated with keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. MUC2, a secretory or gel forming glycoprotein expressed predominantly in goblet cells of the gastrointestinal and respiratory tracts, is overexpressed as an aberrant or deglycosylated form in various tumors such as gastric carcinomas and some hormone-refractory prostate cancers. MUC2 protein is conjugated with KLH, an immunostimulant and a hapten carrier, to enhance immune recognition. Vaccination with MUC2-KLH may result in the production of antibodies as well as elicit a cytotoxic T- lymphocyte (CTL) response against tumor cells expressing MUC2.
A mixed backbone oligonucleotide exhibiting antitumor activity. GEM-231 is complementary to the RI alpha subunit of Protein Kinase A (PKA), resulting in downregulation of PKA expression and ultimately tumor growth. (NCI)
A malignant neoplasm that has spread from its original site of growth to nearby tissues or lymph nodes.
A melanoma peptide vaccine with potential antineoplastic activity. Peptide 946 melanoma vaccine contains one of the peptide sequences for a melanoma-specific epitope that is recognized by melanoma-specific cytotoxic T lymphocytes (CTL). This vaccine contains a peptide sequence homologous to the native epitope and is often formulated with an adjuvant such as QS-21 or Montanide ISA-51 to boost its immune stimulation. Vaccination with peptide 946 vaccine may produce antibodies as well as elicit a cytotoxic T- lymphocyte (CTL) response against cells expressing this antigen, resulting in decreased tumor cell growth.
A melanoma peptide vaccine complexed with tetanus toxoid with potential antineoplastic activity. Peptide 946 contains a melanoma-specific epitope recognized by melanoma-specific cytotoxic T lymphocytes (CTL). In addition to the peptide 946 sequence, this vaccine contains tetanus toxin, a protein known to stimulate the induction of CD4+ T lymphocytes; it thereby enhances antigen processing and presentation. Vaccination with the peptide 946-tetanus conjugate melanoma vaccine may produce antibodies as well as elicit a cytotoxic T lymphocyte (CTL) response in tumor cells expressing the 946 epitope, thereby decreasing tumor cell growth.
A vaccine consisting of peptides derived from melanoma-associated antigens and a modified T-cell epitope derived from tetanus toxoid. Vaccination with this agent may stimulate a host cytotoxic and helper T-cell response against tumor cells expressing melanoma-associated antigens, resulting in decreased tumor growth. (NCI04)
A humanized murine monoclonal antibody (MoAb) against the 17-1A antigen, with potential adjuvant therapeutic properties in colorectal cancer. 17-1A antigen (EpCAM), a human epithelial cell adhesion molecule, expresses in a variety of carcinoma tissues, such as those of colon and breast carcinomas. Immunization with MoAb 3622W94 may elicit immune responses, which could result in eradicating tumor cells expressing 17-1A antigen.
A replication-defective adenoviral-CMV vector that encodes a wild-type p53 gene. Ad5CMV-p53 induces tumor cells that have been transfected with the vector to produce wild-type p53, a tumor suppressor gene that is deleted or mutated in a significant number of cancers. In transfected tumor cells, the wild-type p-53 gene product exerts an antitumor effect by blocking cell cycle progression at the G1/S regulation point, activating DNA repair proteins in the presence of DNA damage, and initiating apoptosis when DNA damage is irreparable. (NCI04)
A recombinant disulfide stabilized anti-Lewis Y IgG immunotoxin containing a 38 KD toxic element derived from the Pseudomonas aeruginosa exotoxin A and a monoclonal antibody fragment, designed to target adenocarcinomas expressing Lewis Y. LMB-9 immunotoxin attaches to tumor cells, facilitating he entry of the exotoxin. The exotoxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis.
A clinical finding that a lymph node is free from cancer spread.
A cancer vaccine consisting of dendritic cells harvested from a patient with cancer and pulsed or transduced with a peptide fragment of carcinoembryonic antigen (CEA), a tumor-associated antigen expressed by a wide range of cancers. When the altered dendritic cells are returned to the patient, they may stimulate the host immune system to mount a cytotoxic T-lymphocyte immune response against tumor cells expressing CEA.
The lactate salt form of squalamine, an aminosterol isolated from tissues of the dogfish shark Squalus acanthias. Possessing anti-angiogenic properties, squalamine inhibits the sodium-hydrogen exchanger NHE3, resulting in suppression of endothelial cell proliferation and migration. This agent also has broad-spectrum antimicrobial properties. (NCI04)
Stage I includes: T1, N0, M0. T1: Tumor 5 cm or less in greatest dimension, no extra-adrenal invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor greater than 5 cm, no extra-adrenal invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, N0, M0). T1: Tumor 5 cm or less in greatest dimension, no extra-adrenal invasion. T2: Tumor greater than 5 cm, no extra-adrenal invasion. T3: Tumor of any size with local invasion, but not invading adjacent organs. N1: Metastasis in regional lymph node(s). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: (T3, N1, M0); (T4, N0, M0); (T4, N1, M0); (Any T, Any N, M1). T3: Tumor of any size with local invasion, but not invading adjacent organs. T4: Tumor of any size with invasion of adjacent organs. N1: Metastasis in regional lymph node(s). N0: No regional lymph node metastasis. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
A vaccine containing a clustered pancarcinoma carbohydrate antigen conjugated with keyhole limpet hemocyanin (KLH) with potential antineoplastic activity. Alpha-N-acetylgalactosamine (Tn) is a monosaccharide usually O-linked to serine or threonine residues of mucins found on most epithelial cancers with the highest expression on prostate cancer. This vaccine contains the Tn epitope cluster (c) that is synthesized by linking 3 copies of the Tn epitope on a threonine backbone to achieve the essential immunogenic structure. KLH is a hapten carrier and serves as an immunostimulant to improve immune recognition. Vaccination with Tn(c)-KLH vaccine may produce antibodies and elicit a cytotoxic T lymphocyte (CTL) response against those tumor cells expressing Tn antigen, resulting in decreased tumor growth.
Any one of the family of genetically engineered chimeric molecules with strong activity in promoting megakaryocyte development. Promegapoietin consists of a truncated or modified interleukin-3 (IL-3) peptide, via a hinge peptide sequence from IgG, linked to multiple repeats of modified thrombopoietin (c-Mpl ligand). This agent is capable of activating megakaryocyte progenitor cells into producing platelets mediated through either IL-3 receptor or Mpl receptor.
A radioimmunoconjugate of the humanized IgG1 monoclonal antibody (MoAb) LL2 labeled with Technetium 99m (Tc-99m). Epratuzumab (MoAb LL2) recognizes CD22, a B-lymphocyte-restricted antigen expressed as a cytoplasmic protein in progenitor B cells, and as a cell surface protein in mature B cells. Tc-99m epratuzumab delivers gamma emission Tc-99m directly to B-lymphocyte lineage cells, thereby the agent may be used for diagnostic or treatment purposes.
A murine IgG monoclonal antibody against the external domain of the prostate-specific membrane antigen (PSMA), overexpressed in the malignant prostate and its metastases. Although PSMA is not a biomarker of disease progression, over-expression indicates an aggressive phenotype of the prostate cancer. Radiolabelled MoAb muJ591 may be used in prostate cancer diagnosis and therapy.
A radioimmunoconjugate of a humanized monoclonal antibody (MoAb) A33 labelled with Iodine 131 (I-131). MoAb A33 recognizes A33 antigen, a 43 KDa transmembrane glycoprotein of the immunoglobulin superfamily, highly and homogenously expressed in 95% of colorectal cancers, with only restricted expression in normal colonic mucosa. Using MoAb A33 as a carrier for I-131 results in the targeted imaging and/or destruction of cells expressed A33 antigen.
A small molecule containing 2 phenol rings, characterized as a hapten for use in vaccine preparation. Dinitrophenyl by itself will not elicit any immune response nor bind to any antigen. Dinitrophenyl compound is commonly used to couple with peptides in vaccine preparation to enhance the immunogenicity of otherwise weak immunogenic antigens.
A synthetic pentafluorophenylsulfonamide with potential antineoplastic activity. T138067 covalently binds to and selectively modifies the beta 1, beta 2, beta 3, and beta 4 isotypes of beta tubulin at a conserved cysteine residue, resulting in disruption of microtubule polymerization, collapse of the cytoskeleton, an increase in chromosomal ploidy, cell cycle arrest, and tumor cell apoptosis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43107&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43107&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1835"" NCI Thesaurus)
brand name of Paclitaxel an anti-cancer drug
A kind of anemia characterized by inadequate production of erythrocytes. [HPO:probinson]
A gestational trophoblastic disorder in which there is no embryo or normal placental tissue and the chorionic villi are hydropic.
A carcinoma arising from the breast, most commonly the terminal ductal-lobular unit. It is the most common malignant tumor in females. Risk factors include country of birth, family history, menstrual and reproductive history, fibrocystic disease and epithelial hyperplasia, exogenous estrogens, contraceptive agents, and ionizing radiation. The vast majority of breast carcinomas are adenocarcinomas (ductal or lobular). Breast carcinoma spreads by direct invasion, by the lymphatic route, and by the blood vessel route. The most common site of lymph node involvement is the axilla.
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
A disease that affects fewer than 200,000 people in the United States.
Drugs or chemical agents whose manufacture, possession, or use are regulated by government. This may include narcotics and prescription medications.
Contact with a chemical substance through touch, inhalation, or ingestion.
A series of thoughts that are difficult to suppress and may be a consequence or cause of anxiety.
Negative opinion about oneself characterized by low self-confidence and exaggeratedly critical feelings about oneself.
Pathological persistent sexual disinhibiting behavior, directed at oneself or to others.
An illness that has a prognosis of death.
A tumor (abnormal growth of tissue) of the genital system.
A non-neoplastic or neoplastic disorder which occurs during infancy, childhood, or adolescence.
Narrowing of the lumen of an artery or vein.
loss of or impaired ability to smell; may be caused by olfactory nerve diseases, paranasal sinus diseases, viral respiratory tract infections, craniocerebral trauma, smoking, and other conditions.
Incorrect conclusion as to source or cause of illness.
Student's unsuccessful attempt at academic achievement or a marked inadequacy in the areas of scholarship or study. This is not underachievement which is performance, usually in school work, poorer than that predicted from aptitude and/or intelligence testing.
Indicates that preschool is the highest level of education achievement.
Indicates that kindergarten is the highest level of education achievement.
Assigment of spiritual faith affiliation.
Employment involving less than the standard or customary working time.
Employed for a standard number of hours of working time, at least 50% or 20 hours per week
A series of chemical modifications of a drug compound by enzymatic activity that make the substrate (drug) more water soluble to allow its clearance from the body. Drug metabolism occurs in two phases: Phase I (biotransformation) involves oxidation, hydroxylation reduction, and hydrolysis. Phase II (conjugation) involves synthesis and conjugation.
State of severe distress associated with events that threaten the intactness of the person, can be physical, mental, or emotional.
A disorder characterized by persistent or recurrent episodes of feeling detached from one's self (either one's body or one's mental processes), although the sufferer remains aware that this is only a feeling and does not represent reality.
A description of the physiological status of a patient.
Person declares that a domestic partner relationship exists
A disorder characterized by involuntary and irregular muscle contractions not associated with muscle weakness or atrophy. It most often affects facial muscles. It may be localized or generalized.
Lung cancer is the leading cause of cancer deaths in the U.S. and worldwide. The 2 major forms of lung cancer are nonsmall cell lung cancer and small cell lung cancer (see 182280), which account for 85% and 15% of all lung cancers, respectively. Nonsmall cell lung cancer can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. Cigarette smoking causes all types of lung cancer, but it is most strongly linked with small cell lung cancer and squamous cell carcinoma. Adenocarcinoma is the most common type in patients who have never smoked. Nonsmall cell lung cancer is often diagnosed at an advanced stage and has a poor prognosis (summary by Herbst et al., 2008).
Mass of alcohol per unit of BLOOD volume.
Hemophilia is a bleeding disorder that slows the blood clotting process. People with this condition experience prolonged bleeding or oozing following an injury, surgery, or having a tooth pulled. In severe cases of hemophilia, continuous bleeding occurs after minor trauma or even in the absence of injury (spontaneous bleeding). Serious complications can result from bleeding into the joints, muscles, brain, or other internal organs. Milder forms of hemophilia do not necessarily involve spontaneous bleeding, and the condition may not become apparent until abnormal bleeding occurs following surgery or a serious injury.The major types of this condition are hemophilia A (also known as classic hemophilia or factor VIII deficiency) and hemophilia B (also known as Christmas disease or factor IX deficiency). Although the two types have very similar signs and symptoms, they are caused by mutations in different genes. People with an unusual form of hemophilia B, known as hemophilia B Leyden, experience episodes of excessive bleeding in childhood but have few bleeding problems after puberty.
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Return to a former state; a subsidence of the symptoms of a disease process; in cancer, a decrease in the size of a tumor or in the extent of cancer in the body.
Phosphoglycerate kinase deficiency is a genetic disorder that affects the body's ability to break down the simple sugar glucose, which is the primary energy source for most cells. Researchers have described two major forms of the condition. The most common form is sometimes called the hemolytic form. It is characterized by a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely. Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), fatigue, shortness of breath, and a rapid heart rate. Some people with the hemolytic form also have symptoms related to abnormal brain function, including intellectual disability, seizures, and stroke.The other form of phosphoglycerate kinase deficiency is often called the myopathic form. It primarily affects muscles, causing progressive weakness, pain, and cramping, particularly with exercise. During exercise, muscle tissue can be broken down, releasing a protein called myoglobin. This protein is processed by the kidneys and released in the urine (myoglobinuria). If untreated, myoglobinuria can lead to kidney failure.Most people with phosphoglycerate kinase deficiency have either the hemolytic form or the myopathic form. However, other combinations of signs and symptoms (such as muscle weakness with neurologic symptoms) have also been reported.
The Ewing sarcoma family of tumors (primitive neuroectodermal tumors; PNET) comprise morphologically heterogeneous tumors that are characterized by nonrandom chromosomal translocations involving the EWS gene on chromosome 22q12 and one of several members of the ETS family of transcription factors. The tumors include Ewing sarcoma, peripheral neuroepithelioma, and Askin tumor. In approximately 90% of cases of ESFT, the FLI1 gene (193067) on chromosome 11 is the fusion partner of EWS; in approximately 10%, the EWS fusion partner is the ERG gene (165080) on chromosome 22. Many other ETS family members have been identified as fusion partners of EWS, but these cases are rare (Khoury, 2005).
The term pseudophakia refers to having an artificial lens implanted after the natural eye lens has been removed. During cataract surgery the natural cloudy lens is replaced by an pseudophakia intraocular lens (IOL). [https://nei.nih.gov/faqs/cataract-pseudophakia]
A neoplasm that arises from the bone or articular cartilage and does not invade adjacent tissues or metastasize to other anatomic sites.
The spread of a malignant neoplasm to the spine. This may be from a primary spinal malignant neoplasm, or from a malignant neoplasm at a distant site.
A malignant neoplasm that has spread to the sternum from another anatomic site.
A malignant neoplasm affecting the skeletal or smooth muscles. Malignant neoplasms arising from the skeletal muscles are called rhabdomyosarcomas. Malignant neoplasms arising from the smooth muscles are called leiomyosarcomas.
A non-metastasizing neoplasm that arises from the neck region.
A malignant neoplasm that has spread to the neck region from a malignancy in a local or distant anatomic site.
A non-metastasizing neoplasm that arises from the structures of the axilla.
A malignant neoplasm that has spread to the structures of the axilla from another anatomic site.
A non-metastasizing neoplasm that arises from the chest wall.
A malignant neoplasm that has spread to the structures of the chest wall from another primary anatomic site.
A malignant neoplasm that has spread to the pharynx from another anatomic site.
A malignant neoplasm that has spread to the hypopharynx from another anatomic site.
A non-metastasizing neoplasm that arises from the pyriform sinus.
A malignant neoplasm that has spread to the larynx from another anatomic site.
A malignant neoplasm that has spread to the trachea from another anatomic site.
A non-metastasizing neoplasm that arises from the hilar region of the lung.
A malignant neoplasm that has spread to the heart from another primary anatomic site.
A non-metastasizing neoplasm that affects the inner layer of the pericardium.
A non-metastasizing neoplasm that arises from the pericardium.
A malignant neoplasm that has spread to the pericardium from another primary anatomic site.
A benign neoplasm arising from arteries or veins.
A hemangioma arising from the subcutaneous soft tissues.
Failure to complete ossification (maturation and calcification) of the palatine bone.
A congenital deformity characterized by the presence of hypoplastic radius. It is usually associated with club hand deformity.
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
A congenital fissure of both the thoracic and abdominal walls.
A congenital fissure of the thoracic wall.
An anomaly of the ischium, which forms the lower and back part of the hip bone.
Failure to complete ossification (maturation and calcification) of the pubic bone.
Defects in the formation of pulmonary lobules.
A congenital heart defect resulting from deficient growth or failure of fusion of the muscular component of the ventricular septum.
A congenital abnormality consisting of clefting in the lower face through the midline of the lip and/or mandible, which results from incomplete fusion of the embryonic mandibular prominence.
A congenital abnormality consisting of an opening or gap in the face, which results from incomplete fusion of one or more of the embryonic facial prominences.
An indication that the anogenital distance is greater than the norm.
Perrault syndrome is a rare condition that causes different patterns of signs and symptoms in affected males and females. A key feature of this condition is hearing loss, which occurs in both males and females. Affected females also have abnormalities of the ovaries. Neurological problems occur in some affected males and females.In Perrault syndrome, the problems with hearing are caused by changes in the inner ear, which is known as sensorineural hearing loss. The impairment usually affects both ears and can be present at birth or begin in early childhood. Unless hearing is completely impaired at birth, the hearing problems worsen over time.Females with Perrault syndrome have abnormal or missing ovaries (ovarian dysgenesis), although their external genitalia are normal. Severely affected girls do not begin menstruation by age 16 (primary amenorrhea), and most never have a menstrual period. Less severely affected women have an early loss of ovarian function (primary ovarian insufficiency); their menstrual periods begin in adolescence, but they become less frequent and eventually stop before age 40. Women with Perrault syndrome may have difficulty conceiving or be unable to have biological children (infertile).Neurological problems in individuals with Perrault syndrome can include intellectual disability, difficulty with balance and coordinating movements (ataxia), and loss of sensation and weakness in the limbs (peripheral neuropathy). However, not everyone with this condition has neurological problems.
A form of the neural tube defect spina bifida in which the entire spinal column is open.
A rare congenital abnormality characterized by the failure of the embryonic prosencephalon to separate the eye orbit into two distinct cavities. Facial features tend to be absent although a proboscis has been seen to develop in conjunction.
Abnormal shortness of the vertical dimensions of the eyelids.
Isolated congenital asplenia is a rare cause of primary immunodeficiency. Most affected individuals die of severe bacterial infections in early childhood. Isolated asplenia is distinct from asplenia associated with other complex visceral defects, notably heterotaxy syndromes such as Ivemark syndrome (208530) (summary by Mahlaoui et al., 2011).
Absence of the thymus. This feature may be appreciated by the lack of a thymic shadow upon radiographic examination.
A congenital anatomic defect characterised by the presence of a proboscis-like nose located above the eyes, which are partially or completely fused.
A congenital defect characterized by the absence of most or all of the head, with the presence of a mouth-like opening on the upper thorax.
Food-induced anaphylaxis is a severe, potentially fatal, systemic allergic reaction that occurs suddenly after contact with an allergy-causing food. [PMID:16461139]
Parotitis that is caused by a bacterial agent.
A primary or metastatic malignant neoplasm involving any part of the digestive system.
A malignant neoplasm that has spread to the lip from another anatomic site.
A non-metastasizing neoplasm that arises from the submandibular gland.
A malignant neoplasm that has spread to the oropharynx from another anatomic site.
A malignant neoplasm that has spread to the esophagus from another organ or system, or from another primary esophageal tumor. The primary esophageal tumor is not in continuity with the metastatic lesion. Representative examples of metastatic cancers to the esophagus include breast and lung metastatic carcinomas and melanomas.
A malignant neoplasm that has spread to the stomach from another organ or system, or from another primary gastric tumor. The primary gastric tumor is not in continuity with the metastatic lesion. Representative examples of metastatic malignant neoplasms to the stomach include breast, lung, and esophageal metastatic carcinomas and melanomas.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
An epithelial or non-epithelial malignant neoplasm which has spread to the anus from another anatomic site.
A malignant neoplasm that has spread to the gallbladder from another anatomic site. Representative examples include metastatic melanoma, and metastatic carcinomas from the breast and the stomach.
A malignant neoplasm that has spread to the extrahepatic bile ducts from another anatomic site. Representative examples include metastatic melanoma and metastatic breast and gastric carcinomas.
A non-metastasizing neoplasm that arises from the organs that comprise the urinary system. Representative examples include renal oncocytoma, bladder inverted papilloma, and urothelial papilloma.
A neoplastic endometrial proliferation that is confined to the endometrium and does not have metastatic potential.
A non-metastasizing neoplasm that arises from the placenta. Representative examples include hemangioma and polyp.
Stage 0 includes: (Tis, N0, M0). Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.)
A marked difference between the individual's expressed/experienced gender and the gender others would assign him or her, and it must continue for at least six months. (from DSM-5)
Tardive dyskinesia is a debilitating motor disorder manifest as hyperkinetic, involuntary, repetitive movements predominantly of the orofacial region. It is a complication of treatment with so-called typical antipsychotic or neuroleptic agents, such as chlorpromazine or haloperidol, and is estimated to occur in 20 to 30% of chronic schizophrenics on long-term treatment (Thelma et al., 2008).
Limb-girdle muscular dystrophy is a term for a group of diseases that cause weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs.The severity, age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition and may be inconsistent even within the same family. Signs and symptoms may first appear at any age and generally worsen with time, although in some cases they remain mild.In the early stages of limb-girdle muscular dystrophy, affected individuals may have an unusual walking gait, such as waddling or walking on the balls of their feet, and may also have difficulty running. They may need to use their arms to press themselves up from a squatting position because of their weak thigh muscles. As the condition progresses, people with limb-girdle muscular dystrophy may eventually require wheelchair assistance.Muscle wasting may cause changes in posture or in the appearance of the shoulder, back, and arm. In particular, weak shoulder muscles tend to make the shoulder blades (scapulae) ""stick out"" from the back, a sign known as scapular winging. Affected individuals may also have an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis). Some develop joint stiffness (contractures) that can restrict movement in their hips, knees, ankles, or elbows. Overgrowth (hypertrophy) of the calf muscles occurs in some people with limb-girdle muscular dystrophy.Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle muscular dystrophy. Some affected individuals experience mild to severe breathing problems related to the weakness of muscles needed for breathing. In some cases, the breathing problems are severe enough that affected individuals need to use a machine to help them breathe (mechanical ventilation).Intelligence is generally unaffected in limb-girdle muscular dystrophy; however, developmental delay and intellectual disability have been reported in rare forms of the disorder.
A malignant neoplasm that has spread to the central nervous system from another anatomic site or system. The majority are carcinomas (usually lung or breast carcinomas).
A malignant neoplasm that has spread from its original site of growth to the brain stem.
A malignant neoplasm that has spread to the retina from another anatomic site.
A malignant neoplasm arising from the parathyroid glands that has spread to other anatomic sites.
A non-metastasizing neoplasm arising from the adrenal medulla. (NCI05)
Burkitt lymphoma that involves the spleen.
History of leukemia after therapy with no evidence on the peripheral blood or bone marrow of leukemia (normalization of all hematologic parameters).
Acute leukemia not growing; responding to treatment.
Leukemia that is no longer growing or metastasizing; it is responding to therapy.
Myeloid leukemia not growing, responding to treatment.
Lymphoid leukemia not growing, responding to treatment.
Erythroleukemia that is responding to therapy, i.e. It is not progressing and possibly regressing.
A non-metastasizing neoplasm that arises from the spleen.
A malignant neoplasm that has spread to the thymus from another anatomic site.
The spread of a malignant neoplasm to the lymph nodes.
A finding of a fusion of two approximately spherical primary ossification centers at or near the mid-line through an ossified bony bridge, as indicated by staining.
A finding of two unfused primary ossification centers, as indicated by staining, usually resulting in two separate and distinct bones.
Break in the continuity of feeding milk from the breasts, which may compromise breastfeeding success and/or nutritional status of the infant/child.
A graft transferred to the same anatomic site in another individual.
Connectedness with self, others, higher power, all life, nature, and the universe that transcends and empowers the self
The nephronophthisis (NPH) phenotype is characterized by reduced renal concentrating ability, chronic tubulointerstitial nephritis, cystic renal disease, and progression to end-stage renal disease (ESRD) before age 30 years. Three age-based clinical subtypes are recongnized: infantile, juvenile, and adolescent/adult. Infantile NPH can present in utero with oligohydramnios sequence (limb contractures, pulmonary hypoplasia and facial dysmorphisms) or postnatally with renal manifestations that progress to ESRD before age 3 years. Juvenile NPH, the most prevalent subtype, typically presents with polydipsia and polyuria, growth retardation, chronic iron-resistant anemia, or other findings related to chronic kidney disease (CKD). Hypertension is typically absent due to salt wasting. ESRD develops at a median age of 13 years. Ultrasound findings are increased echogenicity, reduced corticomedullary differentiation, and renal cysts (in 50% of affected individuals). Histologic findings include tubulointerstitial fibrosis, thickened and disrupted tubular basement membrane, sporadic corticomedullary cysts, and normal or reduced kidney size. Adolescent/ adult NPH is clinically similar to juvenile NPH, but ESRD develops at a median age of 19 years. Within a subtype inter- and intrafamilial variability in rate of progression to ESRD is considerable. Approximately 80%-90% of individuals with the NPH phenotype have no extrarenal features (i.e., they have isolated NPH); ~10%-20% have extrarenal manifestations that constitute a recognizable syndrome (e.g., Joubert syndrome, Bardet-Biedl syndrome, Jeune syndrome and related skeletal disorders, Meckel-Gruber syndrome, Senior-Løken syndrome, Leber congenital amaurosis, COACH syndrome, and oculomotor apraxia, Cogan type).
Alteration of the disposition and/or effect of a drug, owing to the presence of another factor such as a second drug, or food.
The spectrum of CDC73-related disorders includes the following phenotypes: Hyperparathyroidism-jaw tumor (HPT-JT) syndrome. Primary hyperparathyroidism, the main finding of HPT-JT syndrome, occurs in up to 95% of affected individuals; onset is typically in late adolescence or early adulthood. HPT-JT-associated primary hyperparathyroidism is usually caused by a single parathyroid adenoma. In approximately 10%-15% of individuals, primary hyperparathyroidism is caused by parathyroid carcinoma. Ossifying fibromas of the mandible or maxilla, also known as cementifying fibromas and cemento-ossifying fibromas, occur in 30%-40% of individuals with HPT-JT syndrome. Although benign, these tumors can be locally aggressive and may continue to enlarge if not treated. Approximately 20% of individuals with HPT-JT syndrome have kidney lesions, most commonly cysts; renal hamartomas and (more rarely) Wilms tumor have also been reported. Benign and malignant uterine tumors appear to be common in women with HPT-JT syndrome. Parathyroid carcinoma. Most parathyroid carcinomas are functional, resulting in hyperparathyroidism and a high serum calcium level; however, non-functioning parathyroid carcinomas are also rarely described in individuals with a CDC73-related disorder. A germline CDC73 pathogenic variant has been identified in 20%-29% of individuals with apparently sporadic parathyroid carcinoma. Familial isolated hyperparathyroidism (FIHP). FIHP is characterized by primary hyperparathyroidism without other associated syndromic features. Individuals with CDC73-related FIHP tend to have a more severe clinical presentation and younger age of onset than individuals with FIHP in whom a CDC73 pathogenic variant has not been identified.
disturbance of structure, function, or both of the anus and/or rectum.
Painful sensation in the gastrointestinal region.
Neurohypophyseal diabetes insipidus is an autosomal dominant disorder of free water conservation characterized by childhood onset of polyuria and polydipsia. Affected individuals are apparently normal at birth, but characteristically develop symptoms of vasopression deficiency during childhood (summary by Wahlstrom et al., 2004).
Acanthocytosis is a type of poikilocytosis characterized by the presence of spikes on the cell surface. The cells have an irregular shape resembling many-pointed stars.
Activities performed to obtain licit or illicit substances.
AF that cannot be successfully terminated by cardioversion, and longstanding (more than 1 year) AF, where cardioversion is not indicated or has not been attempted, is termed permanent.
Abnormal enlargement of the heart resulting from long-standing hypertension.
Pneumonia that is not acquired in a hospital or long-term care facility setting.
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia. [HPO:probinson, pmid:15750465]
A state of abnormally strong desire for sleep during the daytime. []
A form of reactive arthritis in which the inflammation moves between joints.
Loss or absence of normal intestinal function due to nerve damage or birth defects. It is characterized by the inability to control the elimination of stool from the body.
A Chinese herbal medicine (CHM) containing the root of the perennial herbaceous plant Astragalus (Radix Astragali) belonging to the family Leguminosae. Huang Qi is believed to tonify Qi, induce diuresis, relieve edema and nourish blood. It may also replenish body fluids and help relieve pain.
A Chinese herb of a desiccated root from the plant Coptis chinensis. Although the mechanism of action remains to be fully elucidated, Huang Lian has antibacterial, antifungal, and antiprotozoal activities. In addition, this herb exhibits antioxidant property that influences positively on lipid metabolism, cause dilation of blood vessels, and may slow the growth of tumor cells. This herb contains rich amount of phytogens, such as berberine, palmatine, jatrorrhizine, columbamine, geniposide, and anti-HIV compound baicalin, which might explain the broad effects of this herb. Huang Lian is commonly used to treat diarrhea or dysentery in Chinese medicine.
Dried ripe fruit of Evodia ruticarpa that is used in DRUGS, CHINESE HERBAL.
The hydrochloride form of labetalol, a third generation selective alpha-1-adrenergic antagonist and non-selective beta-adrenergic antagonist with vasodilatory and antihypertensive properties. Labetalol competitively binds to alpha-1-adrenergic receptors in vascular smooth muscle, thereby inhibiting the adrenergic stimulation of endothelial cell function and vasoconstriction in peripheral blood vessels. This agent also binds to beta-receptors in the bronchial and vascular smooth muscle, resulting in a decrease in adrenergic stimulation. The result is a decrease in resting and exercise heart rates, cardiac output, and in both systolic and diastolic blood pressure, thereby resulting in vasodilation, and negative chronotropic and inotropic cardiac effects.
brand name of a synthetic female sex hormone
estrogen supplement drug used to relieve menopausal symptoms
group of peripheral nervous system hereditary disorders with varying course, symptoms, neuropathology, and genetics, but characterized by degeneration of peripheral nerves, and clinically by loss of sensation.
A viral or bacterial infection that affects the external, middle, or inner ear. It may follow an upper respiratory infection. Signs and symptoms include pain, ear discharge, ear fullness, hearing loss, vertigo, nausea, and vomiting.
The pathologic, physiologic, or biochemical mechanism resulting in the development of a disease or morbid process.
A cancer arising in any part of the stomach.
A highly purified alpha interferon produced by a human lymphoid cell line. Interferon alpha-n1 consists of multiple alpha interferon subtypes, at least two of which are glycosylated. In contrast, recombinant alpha interferons are individual non-glycosylated proteins produced from individual alpha interferon genes. Alpha interferons bind to specific cell-surface receptors, resulting in the transcription and translation of genes whose proteins have antiviral, antiproliferative, anticancer, and immune-modulating effects. (NCI04)
A carcinoma arising from the bladder epithelium. Approximately 90% of the bladder carcinomas are transitional cell carcinomas. The remainder are squamous cell carcinomas, adenocarcinomas and small cell neuroendocrine carcinomas.
A primary or metastatic malignant neoplasm involving the female reproductive system. Representative examples include endometrial carcinoma, cervical carcinoma, ovarian carcinoma, uterine corpus leiomyosarcoma, adenosarcoma, malignant mixed mesodermal (mullerian) tumor, and gestational choriocarcinoma.
A carcinoma that arises from the skin. Representative examples are basal cell carcinoma and squamous cell carcinoma.
A standardized, concentrated preparation, by Purdue, containing the anthraquinone glycosides sennosides extracted from senna leaves with laxative activity. Sennosides act on and irritate the lining of the intestine wall, thereby causing increased intestinal muscle contractions leading to vigorous bowel movement.
An inability to be still and/or the need to move.
Reduction of neurologic reflexes such as the knee-jerk reaction.
Malignant epithelial neoplasm arising from the urethra (lower urinary tract).
A carcinoma that has spread to the bone from another, primary anatomic site. Bone is one of the most frequent sites of metastatic carcinoma. Common sites of origin include lung, breast, and prostate.
The condition of being dilated or stretched.
Any vaccine derived from Neisseria meningitidis whether in whole-cell or acellular form used for prophylaxis against meningitis.
Inspiration of a foreign object into the airway.
An episode of lightheadedness and dizziness which may precede an episode of syncope.
A broad category of sleep disorders characterized by either hypersomnolence or insomnia. The three major subcategories include intrinsic (i.e., arising from within the body) (SLEEP DISORDERS, INTRINSIC), extrinsic (secondary to environmental conditions or various pathologic conditions), and disturbances of circadian rhythm. (From Thorpy, Sleep Disorders Medicine, 1994, p187)
An increased amount of creatinine in the blood.
A brachial plexus disorder characterized by regional paresthesia, pain and muscle weakness, and limited movement in the arm or hand.
A finding indicating decreased oxygen levels in the blood.
This is a form of nonspherocytic hemolytic anemia of Dacie type I (in vitro autohemolysis is not corrected by added glucose). After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies; 208530).
A light microscopic finding that describes the cellular characteristics and architectural patterns of cell populations in a tissue sample.
Infection of the VULVA and VAGINA with a fungus of the genus CANDIDA.
The sodium salt of pentobarbital, a short-acting barbituric acid derivative with central nervous system (CNS) depressant property. Pentobarbital sodium binds to the gamma-aminobutyric acid (GABA)-A subtype receptor, resulting in modulation of chloride transport through receptor channels and potentiation of GABA-induced increases in chloride conductance. This enhances postsynaptic responses to the inhibitory actions of GABA and causes CNS depression. In addition, this agent inhibits glutamate induced nerve depolarization and depresses voltage-activated calcium currents.
Disturbed mental state characterized by moodiness, irritability, agitation, anxiety, and/or depression resulting from physical or mental stress.
An electrocardiographic finding of three or more consecutive complexes of ventricular origin with a rate less than a certain threshold (100 or 120 beats per minute are commonly used). The QRS complexes are wide and have an abnormal morphology. (CDISC)
A highly malignant embryonal tumor of infancy and young childhood characterized by neuroectodermal elements organized in distinctive multilayered rosettes. Ependymoblastomas are large lesions that occur in the supratentorial compartment, typically displaying a physical connection to the ventricular system.
The hydrochloride salt of an iodine-rich benzofuran derivative with antiarrhythmic and vasodilatory activities. As a class III antiarrhythmic agent, amiodarone blocks the myocardial calcium, potassium and sodium channels in cardiac tissue, resulting in prolongation of the cardiac action potential and refractory period. In addition, this agent inhibits alpha- and beta-adrenergic receptors, resulting in a reduction in sympathetic stimulation of the heart, a negative chronotropic effect, and a decrease in myocardial oxygen demands. Amiodarone may cause vasodilation by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.
The hydrochloride salt of an anxiolytic agent chemically and pharmacologically unrelated to benzodiazepines, barbiturates, or other sedative/hypnotic drugs. Although its exact mechanism of action is unknown, buspirone may exert its anti-anxiety effects via serotonin (5-HT1A) and dopamine receptors (D2) and may indirectly affect other neurotransmitter systems. Unlike typical benzodiazepine anxiolytics, this agent does not exert anticonvulsant or muscle relaxant effects and lacks prominent sedative effects.
The sulfate salt of chloroquine, a quinoline compound with antimalarial and anti-inflammatory properties. Chloroquine is the most widely used drug against malaria, except for those cases caused by chloroquine resistant Plasmodium falciparum. Although the mechanism of action is not fully understood, chloroquine is shown to inhibit the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. Chloroquine may also interfere with the biosynthesis of nucleic acids.
The hydrochloride salt form of dobutamine, a synthetic catecholamine with direct inotropic activity. Dobutamine hydrochloride, mimics the effects of dopamine and stimulates beta-1 adrenergic receptors located in the myocardium. This leads to an increase in heart rate and force and results in an increase in cardiac output.
The maleate salt form of enalapril, a dicarbocyl-containing peptide and angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, enalapril is converted by de-esterification into its active form enalaprilat. Enalaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Enalapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
Fenoterol BromideThe hydrobromide salt of fenoterol, a short-acting sympathomimetic agent with bronchodilator activity. Fenoterol stimulates beta-2-adrenergic receptors in the lungs, thereby activating the enzyme adenylate cyclase that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP concentrations relax bronchial smooth muscle, relieve bronchospasms, and reduce inflammatory cell mediator release, especially from mast cells.
The hydrochloride salt form of maprotiline, a tetracyclic antidepressant closely related to the tricyclic antidepressants with adrenergic activity and sedative properties. Maprotiline hydrochloride exerts its effect by blocking the re-uptake of norepinephrine, thereby increasing the synaptic concentration of norepinephrine in the central nervous system and subsequently prolonging the action of norepinephrine on central receptors.
The hydrochloride salt of a short-acting benzodiazepine derivative with an imidazole structure and anxiolytic, amnestic, hypnotic, anticonvulsant and sedative properties. Midazolam binds to the benzodiazepine receptor at the gamma-aminobutyric acid (GABA) receptor-chloride ionophore complex in the central nervous system (CNS), resulting in increases in the opening of chloride channels, membrane hyperpolarization, and the inhibitory effect of GABA. This agent may also interfere with the reuptake of GABA, thereby causing accumulation of GABA in the synaptic cleft.
The hydrochloride salt of an anthracenedione antibiotic with antineoplastic activity. Mitoxantrone intercalates into and crosslinks DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, resulting in DNA strand breaks and inhibition of DNA repair. Mitoxantrone is less cardiotoxic compared to doxorubicin.
The hydrochloride salt form of nortriptyline, a tricyclic antidepressant agent used for short-term treatment of various forms of depression. Nortriptyline blocks the norepinephrine presynaptic receptors, thereby blocking the reuptake of this neurotransmitter and raising the concentration in the synaptic cleft in the CNS. Nortriptyline also binds to alpha-adrenergic, histaminergic and cholinergic receptors. Long-term treatment with nortriptyline produces a downregulation of adrenergic receptors due to the increased stimulation of these receptors.
The hydrochloride salt form of oxprenolol, a lipophilic, nonselective beta-adrenergic receptor antagonist with anti-arrhythmic, anti-anginal and antihypertensive activities. Oxprenolol competitively binds to and blocks beta-1 adrenergic receptors in the heart, thereby decreasing cardiac contractility and rate. This leads to a reduction in cardiac output and lowers blood pressure. In addition, oxprenolol prevents the release of renin, a hormone secreted by the kidneys that causes constriction of blood vessels.
The hydrochloride salt form of propafenone with class 1C antiarrhythmic effects. Propafenone hydrochloride stabilizes the neuronal membrane by binding to and inhibiting voltage-gated sodium channels, thereby reducing sodium influx required for the initiation and conduction of impulses in Purkinje and myocardial cells. This agent produces a marked depression of phase 0 and prolonged effective refractory period in the atrio-ventricular nodal and His-Purkinje tissue, resulting in a profound decrease in excitability, conduction velocity and automaticity, thereby counteracting atrial and ventricular arrythmias.
The hydrochloride salt form of selegiline, a levorotatory acetylenic derivative of phenethylamine with antiparkinsonian effect. As a selective monoamine oxidase (MAO) inhibitor, selegiline has the greatest affinity for type B MAO, found mainly in the brain. Selegiline is converted by MAO B to an active moiety, which binds irreversibly at the active site of the enzyme's cofactor FAD (flavin adenine dinucleotide) molecule. This prevents the oxidative deamination of catecholamines and serotonin by MAO B, and leads to an increase in these neurotransmitters' activities resulting in improved motor function. In addition, this agent may inhibit re-uptake of dopamine by the neuron and prolong dopamine activity.
The hydrochloride form of Verapamil, which is a phenylalkylamine calcium channel blocking agent. Verapamil inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents. (NCI04)
The hydrochloride salt form of guanfacine, a centrally acting alpha-2 adrenergic agonist with antihypertensive activity. Alpha-2 receptor stimulation by guanfacine hydrochloride results in a decreased sympathetic outflow from the vasomotor center to the heart, kidneys, and peripheral vasculature. This leads to a decrease in heart rate and peripheral vascular resistance. (NCI05)
The maleate salt form of fluvoxamine, a 2-aminoethyl oxime ether of aralkylketones, with antidepressant, antiobsessive-compulsive, and antibulimic activities. Fluvoxamine blocks serotonin reuptake by inhibiting the serotonin reuptake pump of the presynaptic neuronal membrane leading to an increase of serotonin levels within the synaptic cleft. This results in facilitated serotonergic transmission and decreased serotonin turnover leading to antidepressant and antiobsessive-compulsive effects.
The sodium salt of pravastatin with cholesterol-lowering and potential antineoplastic activities. Pravastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent lowers plasma cholesterol and lipoprotein levels, and modulates immune responses by suppressing MHC II (major histocompatibility complex II) on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. In addition, pravastatin, like other statins, exhibits pro-apoptotic, growth inhibitory, and pro-differentiation activities in a variety of tumor cells; these antineoplastic activities may be due, in part, to inhibition of the isoprenylation of Ras and Rho GTPases and related signaling cascades.
The acetate salt of a synthetic decapeptide analog of luteinizing hormone-releasing hormone (LHRH). Continuous, prolonged administration of goserelin in males results in inhibition of pituitary gonadotropin secretion, leading to a significant decline in testosterone production; in females, prolonged administration results in a decrease in estradiol production. (NCI04)
The acetate salt form of nafarelin, a modified synthetic porcine luteinizing hormone (LH)-releasing hormone peptide analog, with gonadotropin-releasing hormone (GnRH) agonist activity. Upon nasal inhalation, nafarelin acetate binds to the GnRH receptor. This initially results in the release of the gonadotropins, follicle-stimulating hormone (FSH) and LH, from the pituitary gland; however, prolonged stimulation of the GnRH receptor desensitizes the receptor, which leads to decreased secretion of FSH and LH. In females, the inhibition of gonadotropin secretion causes hypogonadotropic hypogonadism leading to decreased production of estrogen and progesterone and anovulation. In males, the inhibition of LH secretion prevents the production and release of testosterone from Leydig cells in the testes and causes a significant decline in testosterone production that is near the levels seen following castration.
The hydrochloride salt of the racemic form of ondansetron, a carbazole derivative and a selective, competitive serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist with antiemetic activity. Although its mechanism of action has not been fully characterized, ondansetron appears to competitively block the action of serotonin at 5HT3 receptors peripherally in the gastrointestinal tract as well as centrally in the area postrema of the CNS, where the chemoreceptor trigger zone (CTZ) for vomiting is located, resulting in the suppression of chemotherapy- and radiotherapy-induced nausea and vomiting.
A synthetic phenylmethyl-piperazinyl derivative, antihistaminic Cetirizine is a metabolite of hydroxyzine and a selective peripheral histamine H1-receptor antagonist. It is used for symptomatic treatment of seasonal and perennial allergic rhinitis and for chronic urticaria. (NCI04)
The mesylate salt form of fenoldopam, a benzazepine derivative with rapid-acting vasodilator activity. Fenoldopam mesylate is a racemic mixture of S- and R- isomers; the latter is responsible for the biological activity and has a significantly higher affinity for dopamine D1-like receptors (D1 and D5) as well as moderate affinity to alpha-2 adrenergic receptors. This agent selectively activates the dopamine D1-like receptor, thereby causing vasodilatation and increasing renal perfusion.
The sodium salt of alendronate, a second generation bisphosphonate and synthetic analog of pyrophosphate with bone anti-resorption activity. Alendronate sodium binds to and inhibits the activity of geranyltranstransferase (farnesyl pyrophosphate synthetase), an enzyme involved in terpenoid biosynthesis. Inhibition of this enzyme prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are donor substrates of farnesylation and geranylgeranylation during the post-translational modification of small GTPase signalling proteins, which is important in the process of osteoclast turnover. As a result, osteoclast activity is inhibited and bone resorption and turnover are reduced.
A synthetic antiviral agent. Indinavir selectively binds to the active site of human immunodeficiency virus (HIV) protease and inhibits its activity, preventing the protease-mediated cleavage of gag-pol viral polyproteins; as a result immature, noninfectious virions are produced.
An ester with sympathomimetic activities. Dipivefrin hydrochloride is a prodrug of epinephrine that, due to its greater lipophilicity, allows for better penetration into the anterior chamber. Once inside the eye, dipivefrin hydrochloride is converted by hydrolysis to epinephrine. Epinephrine enhances the outflow of aqueous humor and decreases the production of aqueous humor by vasoconstriction. This leads to a reduction in intraocular pressure.
The potassium salt of losartan, a non-peptide angiotensin II receptor antagonist with antihypertensive activity. Losartan selectively and competitively binds to the angiotensin II receptor (type AT1) and blocks the binding of angiotensin II to the receptor, thus promoting vasodilatation and counteracting the effects of aldosterone. Converted from angiotensin I by angiotensin-converting enzyme (ACE), angiotensin II stimulates the adrenal cortex to synthesize and secrete aldosterone, decreasing sodium excretion and increasing potassium excretion, and acts as a vasoconstrictor in vascular smooth muscle.
The hydrochloride salt form of pyridoxine, a water-soluble vitamin B. Pyridoxine hydrochloride is converted into the active form, pyridoxal 5'-phosphate (PLP), an essential cofactor in many enzymatic activities including synthesis of amino acids, neurotransmitters, and sphingolipids. This vitamin is essential to red blood cell, nervous system, and immune systems functions and helps maintain normal blood glucose levels.
The hydrochloride salt form of thioridazine, a piperidine phenothiazine derivative and a dopamine antagonist with antipsychotic property. Thioridazine hydrochloride binds to mesolimbic postsynaptic dopamine receptor D2, thereby decreasing dopamine activity leading to decreased psychotic effects, such as hallucinations and delusions. In addition, this agent binds to serotonin 5-HT2 receptors, resulting in decreased serotonin activity.
Nystagmus dating from or present at birth.
A type of hypothyroidism that results from a defect in the thyroid gland.
The hydrochloride salt of the tricyclic dibenzocycloheptadiene amitriptyline with antidepressant and antinociceptive activities. Amitriptyline inhibits the re-uptake of norepinephrine and serotonin by the presynaptic neuronal membrane in the central nervous system (CNS), thereby increasing the synaptic concentration of norepinephrine and serotonin. Due to constant stimulation to these receptors, amitriptyline may produce a downregulation of adrenergic and serotonin receptors, which may contribute to the antidepressant activity. In the CNS the antinociceptive activity of this agent may involve high affinity binding to and inhibition of N-methyl-D-aspartate (NMDA) receptors and/or the enhancement of the action of serotonin at the spinal terminals of an opioid-mediated intrinsic analgesia system.
The hydrochloride salt form of chlordiazepoxide, a long-acting benzodiazepine with anxiolytic, sedative and hypnotic activity. Chlordiazepoxide hydrochloride exerts its effect by binding to the benzodiazepine site at the gamma-aminobutyric acid (GABA) receptor-chloride ionophore complex in the central nervous system (CNS). This leads to an increase in the opening of chloride channels, membrane hyperpolarization, and increases the inhibitory effect of GABA on the CNS.
The hydrochloride salt form of desipramine, a secondary amine tricyclic antidepressant (TCA). In the central nervous system (CNS), desipramine hydrochloride blocks the re-uptake of neurotransmitters, including norepinephrine and serotonin. This leads to an increase in the amount of these neurotransmitters in the synaptic cleft and prolongs their activities postsynaptically.
An ergot derivative with agonistic activity for alpha-adrenergic, serotonergic, and dopaminergic receptors. Dihydroergotamine mesylate most likely relieves migraine headaches by binding to and stimulating the 5-HT1D receptor subtype, thereby causing constriction of cerebral blood vessels. However, it has also been proposed that dihydroergotamine mesylate acts upon 5-HT1D receptors on sensory nerve endings of the trigeminal system, thereby decreasing the release of pro-inflammatory neuropeptide release.
The hydrochloride salt form of hydromorphone, the hydrogenated ketone of morphine, a semi-synthetic opioid with analgesic effects. Hydromorphone selectively binds the mu-opioid receptor which is linked through G-proteins. Binding stimulates the exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) on the G-protein complex and interacts with and inhibits adenylate cyclase located at the inner surface of the plasma membrane. This leads to a reduction in intracellular cyclic 3',5'-adenosine monophosphate (cAMP). Further, voltage-gated potassium channels are activated, thereby causing hyperpolarization and reducing neuronal excitability. In addition, the opening of voltage-gated calcium channels is inhibited, thereby leading to an inhibition of calcium entry and a reduction in the release of various neurotransmitters, including GABA, vasopressin, somatostatin, insulin and glucagons.
A class Ia antiarrhythmic agent with cardiac depressant properties. Disopyramide phosphate exerts its actions by blocking both sodium and potassium channels in cardiac membrane during phase 0 of the action potential. This slows the impulse conduction through the AV node and prolongs the duration of the action potential of normal cardiac cells in atrial and ventricular tissues. Disopyramide prolongs the QT interval and causes a widening of the QRS complex. It also possesses some anticholinergic and local anaesthetic properties. Disopyramide phosphate is used in the treatment of supraventricular tachycardia.
A dibenzoxepin derivative and tricyclic antidepressant with antipruritic and sedative activities. Doxepin blocks the reuptake of norepinephrine and serotonin into presynaptic terminals thereby prolonging the availability of the monoaminergic neurotransmitters within the synaptic cleft and enhancing their action leading to sedative effects. Doxepin also has antagonistic effects on histamine (H1 and H2), 5-HT2, alpha-1 adrenergic, and muscarinic receptors. The antipruritic effect of this agent is the result mediated through inhibition of histamine receptors.
The bitartrate salt form of epinephrine, a direct-acting sympathomimetic amine with bronchodilator and vasoconstricting activity. Epinephrine bitartrate acts on both alpha and beta adrenergic receptors. By stimulating alpha adrenergic receptors locally, this agent causes vasoconstriction and reduces vascular blood flow. Administered in the conjunctiva, epinephrine bitartrate induces vasoconstriction and decreases the production of aqueous humor mediated through alpha-adrenergic receptors. Through its beta-stimulating actions, this agent relaxes bronchial smooth muscle and causes bronchodilation.
The pamoate salt form of hydroxyzine, a synthetic piperazine histamine H1-receptor antagonist with anti-allergic, antispasmodic, sedative, anti-emetic and anti-anxiety properties. Hydroxyzine pamoate blocks the H1 histamine receptor and prevents the symptoms that are caused by histamine activity on capillaries, bronchial smooth muscle, and gastrointestinal smooth muscle, including vasodilatation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastrointestinal smooth muscle. In addition, hydroxyzine pamoate crosses the blood-brain barrier and acts on the histamine H1-receptors in the central nervous system. (NCI05)
The sulfate salt of kanamycin, a naturally occurring aminoglycoside antibiotic with antimicrobial property. Derived from Streptomyces kanamyceticus, kanamycin is an antibiotic complex consisting of three components: kanamycin A, the major component (also usually designated as kanamycin), and kanamycins B and C, the minor components. This agent irreversibly binds to the bacterial 30S ribosomal subunit. Specifically, this antibiotic is lodged between 16S rRNA and S12 protein within the 30S subunit. This leads to interference with translational initiation complex, misreading of mRNA, thereby hampering protein synthesis and resulting in bactericidal effect. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.
The hydrochloride salt of a synthetic derivative of cyclohexanone with analgesic and anesthetic activities. Although its mechanism of action is not well understood, ketamine appears to non-competitively block N-methyl-D-aspartate (NMDA) receptors and may interact with opioid mu receptors and sigma receptors, thereby reducing pain perception, inducing sedation, and producing dissociative anesthesia.
The hydrochloride salt form of mepivacaine, an amide derivative with local anesthetic properties. At the injection site, mepivacaine hydrochloride acts by binding to specific membrane sodium ion channels in the neuronal cell membranes, thereby inhibiting sodium influx. This leads to a blockage of nerve impulse conduction and results in a loss of sensation.
The hydrochloride salt of the synthetic central nervous system stimulant methylphenidate. Methylphenidate appears to activate the brain stem arousal system and cortex to produce its stimulant effect and, in some clinical settings, may improve cognitive function.
The sodium succinate salt of a synthetic glucocorticoid receptor agonist with immunosuppressive and anti-inflammatory effects. Methylprednisolone sodium succinate is converted into active prednisolone in the body, which activates glucocorticoid receptor mediated gene expression. This includes inducing synthesis of anti-inflammatory protein IkappaB-alpha and inhibiting synthesis of nuclear factor kappaB (NF-kappaB). As a result, proinflammatory cytokine production such as IL-1, IL-2 and IL-6 is down-regulated and cytotoxic T-lymphocyte activation is inhibited. Therefore, an overall reduction in chronic inflammation and autoimmune reactions may be achieved.
The tartrate salt form of metoprolol, a cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties and devoid of intrinsic sympathomimetic activity. Metoprolol tartrate antagonizes beta 1-adrenergic receptors in the myocardium, thereby reducing the rate and force of myocardial contraction, and consequently a diminished cardiac output. This agent may also reduce the secretion of renin with subsequent reduction in levels of angiotensin II thus decreasing sympathetic activation, including vasoconstriction, aldosterone secretion.
The hydrochloride salt of naloxone, a thebaine derivate with opioid antagonist activity. Naloxone binds to opioid receptors in the CNS in a competitive manner, reversing or inhibiting characteristic opioid effects, including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia, and physical dependence. This agent binds to mu-opioid receptors with a high affinity, and a lesser degree to kappa- and gamma-opioid receptors.
Sodium salt of aminohippuric acid. Aminohippurate sodium is used as a non-toxic diagnostic tool to measure effective renal plasma flow. At low plasma concentration this agent is filtered by the glomeruli and almost completely cleared from the renal blood stream by active tubular secretion in a single transit through the kidney. Its clearance corresponds to the renal plasma blood flow. Aminohippurate sodium is also used to measure functional capacity of the renal tubular secretory mechanism. This is achieved by elevating the drug plasma concentration to levels sufficient to saturate the maximal secretion capacity of the tubular cells.
A synthetic, brick-red crystalline solid that is only slightly soluble in cold water and ethanol but is soluble in boiling water, acetic acid, glycerol, ethylene glycol and propylene glycol. It is used orally as a urinary tract analgesic. Side effects of phenazopyridine hydrochloride administration can include nausea, interference with the oxygen-carrying capacity of red blood cells (methemoglobinemia), hemolytic anemia as well as renal and hepatic toxicity. It is reasonably anticipated to be a human carcinogen. (NCI05)
The hydrochloride salt form of protriptyline, a tricyclic secondary amine with antidepressant property. Protriptyline hydrochloride blocks the re-uptake of norepinephrine and serotonin by nerve terminals, thereby increasing available norepinephrine and serotonin. Protriptyline does not block dopamine transport but may have an indirect dopamine-facilitating effect through interactions of increased peri-synaptic abundance of norepinephrine, particularly in the cerebral cortex, where adrenergic terminals exceed dopaminergic terminals. This results in elevation of mood and behavioral activity. In addition, this agent exhibits anticholinergic activity.
The hydrochloride salt of alfentanil, a synthetic short-acting opioid with analgesic and local anesthesia enhancing activity. Alfentanil primarily binds to mu-opioid receptor, a G-protein-coupled receptor, thereby mimicking the actions of morphine, the prototypical mu receptor agonist. This agent induces anti-nociception responses mediated through inhibiting the release of various neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline; in addition, the release of vasopressin, somatostatin, insulin and glucagon are also inhibited.
The hydrochloride salt of an aminoketone antidepressant. The molecular mechanism of the antidepressant effect of bupropion is unknown. This agent does not inhibit monoamine oxidase and, compared to classical tricyclic antidepressants, is a weak blocker of the neuronal uptake of serotonin and norepinephrine. Buproprion also weakly inhibits the neuronal re-uptake of dopamine.
The hydrochloride salt of fluphenazine, a phenothiazine with antipsychotic activity and potential antineoplastic activity. Fluphenazine blocks postsynaptic dopamine D2 receptors in the limbic system, cortical system and basal ganglia, resulting in a reduction of schizophrenia-associated hallucinations and delusions. In addition, as a serotonin antagonist, this agent may inhibit lymphocyte and myeloma cell proliferation by blocking 5-hydroxytrptamine type 1B (5-HT type 1B) receptors for serotonin.
A synthetic piperazine derivative with hypotensive antiadrenergic properties, Prazosin Hydrochloride reduces peripheral resistance and relaxes vascular smooth muscles as a selective adrenergic alpha-1 antagonist by a mechanism not completely known. It is used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. (NCI04)
A benzothiazepine calcium channel blocking agent. Diltiazem hydrochloride inhibits the transmembrane influx of extracellular calcium ions into select myocardial and vascular smooth muscle cells, causing dilatation of coronary and systemic arteries and decreasing myocardial contractility. Because of its vasodilatory activity, this agent has been shown to improve the microcirculation in some tumors, thereby potentially improving the delivery of antineoplastic agents to tumor cells. (NCI04)
The bromide salt form of ipratropium, a synthetic derivative of the alkaloid atropine with anticholinergic properties. Ipratropium antagonizes the actions of acetylcholine at parasympathetic, postganglionic, effector-cell junctions. When inhaled, ipratropium binds competitively to cholinergic receptors in the bronchial smooth muscle thereby blocking the bronchoconstrictor actions of the acetylcholine mediated vagal impulses. Inhibition of the vagal tone leads to dilation of the large central airways resulting in bronchodilation.
The hydrochloride salt of the 4'-epi-isomer of the anthracycline antineoplastic antibiotic doxorubicin. Epirubicin intercalates into DNA and inhibits topoisomerase II, thereby inhibiting DNA replication and ultimately, interfering with RNA and protein synthesis. This agent also produces toxic free-radical intermediates and interacts with cell membrane lipids causing lipid peroxidation.
The sodium form of DICLOFENAC. It is used for its analgesic and anti-inflammatory properties.
Disease involving a spinal nerve root (see SPINAL NERVE ROOTS) which may result from compression related to INTERVERTEBRAL DISK DISPLACEMENT; SPINAL CORD INJURIES; SPINAL DISEASES; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root.
A group of congenital neurodegenerative disorders affecting motor neurons, resulting in muscle weakness and atrophy in childhood. Signs and symptoms include hypotonia, difficulty breathing, poor feeding, and flaccid quadriplegia.
The acetate salt of a synthetic nonapeptide analogue of gonadotropin-releasing hormone. Leuprolide binds to and activates gonadotropin-releasing hormone (GnRH) receptors. Continuous, prolonged administration of leuprolide in males results in pituitary GnRH receptor desensitization and inhibition of pituitary secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to a significant decline in testosterone production; in females, prolonged administration results in a decrease in estradiol production. This agent reduces testosterone production to castration levels and may inhibit androgen receptor-positive tumor progression.
A combination product containing pyrimethamine and sulfadoxine. Pyrimethamine is a competitive inhibitor of dihydrofolate reductase (DHFR). DHFR is a key enzyme in the redox cycle for production of tetrahydrofolate, a cofactor that is required for the synthesis of DNA and proteins. Sulfadoxine competitively antagonizes paraaminobenzoic acid (PABA), resulting in disruption of folic acid synthesis and ultimately DNA synthesis. Sulfadoxine acts synergistically with pyrimethamine. (NCI04)
An oil extracted from the seeds of the plant Oenothera biennis, a North American native biennial branching shrub with small yellow flowers. The oil contains the fatty acids linoleic acid and gamma-linolenic acid (GLA), a rare essential fatty acid.
The disodium salt of the 21-phosphate ester of betamethasone, a synthetic glucocorticoid with metabolic, immunosuppressive and anti-inflammatory actions. Betamethasone sodium phosphate binds to specific intracellular glucocorticoid receptors and subsequently binds to DNA to modify gene expression. The synthesis of certain anti-inflammatory proteins is induced while the synthesis of certain inflammatory mediators is inhibited. As a result, there is an overall reduction in chronic inflammation and autoimmune reactions.
The hydrochloride salt form of esmolol, a short and rapid-acting beta adrenergic antagonist belonging to the class II anti-arrhythmic drugs and devoid of intrinsic sympathomimetic activity. Esmolol hydrochloride competitively blocks beta-1 adrenergic receptors in cardiac muscle and reduces the contractility and cardiac rate of heart muscle, thereby decreasing cardiac output and myocardial oxygen demands. This agent also decreases sympathetic output centrally and blocks renin secretion. At higher doses, esmolol hydrochloride also blocks beta-2 receptors located in bronchial and vascular smooth muscle, thereby leading to smooth muscle relaxation.
group of disorders genetically distinct from the other inherited hyperlipidemias classified on the basis of type I through V phenotypes; see narrower terms.
The Strudwick type of spondyloepimetaphyseal dysplasia (SEMD) is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (summary by Tiller et al., 1995).
A non-neoplastic, regenerating hepatocellular hyperplasia, secondary to the presence of focal vascular abnormalities in the liver.
An abnormality characterized by thickening of the muscle in the wall of the pylorus. It results in the narrowing of the pyloric channel. The overlying mucosa may appear hypertrophic as well. Clinical signs and symptoms appear early in life and include projectile vomiting and dehydration.
Botox is a drug made from a toxin produced by the bacterium Clostridium botulinum. It's the same toxin that causes a life-threatening type of food poisoning called botulism. Doctors use it in small doses to treat health problems, including. -Temporary smoothing of facial wrinkles and improving your appearance. -Severe underarm sweating . -Cervical dystonia - a neurological disorder that causes severe neck and shoulder muscle contractions . -Blepharospasm - uncontrollable blinking . -Strabismus - misaligned eyes . -Chronic migraine. -Overactive bladder. Botox injections work by weakening or paralyzing certain muscles or by blocking certain nerves. The effects last about three to twelve months, depending on what you are treating. The most common side effects are pain, swelling, or bruising at the injection site. You could also have flu-like symptoms, headache, and upset stomach. Injections in the face may also cause temporary drooping eyelids. You should not use Botox if you are pregnant or breastfeeding.
The hydrochloride salt form of buprenorphine, a synthetic phenanthrene with narcotic analgesic activity. Buprenorphine hydrochloride is a partial agonist at the mu-opioid receptor and an antagonist at the kapa-opioid receptor in the central nervous system. However, under the conditions of recommended use it behaves as a classic mu-opioid agonist, mimicking the actions of endogenous peptides at CNS opioid receptors. The agonist action results in a raised pain threshold and increased tolerance to pain. However, it also causes sedation, physical dependence, and respiratory depressant effects and decreases heart rate and blood pressure.
Inflammation of the uveal tract in which the primary site of inflammation is the anterior chamber.
Presence or formation of GALLSTONES in the COMMON BILE DUCT.
Fetal or infant death during the period of time that includes the antepartum, intrapartum, and neonatal stages.
Agents that are put on the SKIN to reduce SWEATING or prevent excess sweating (HYPERHIDROSIS).
A type of cataract characterised by club-shaped and dot opacities distributed radially in the deep cortex. These lens opacities surround the nucleus in an appearance that is though to resemble a crown. [ORCID:0000-0003-0986-4123]
A morphologic finding referring to the presence of intercellular edema in the epidermal keratinocytes or to the vacuolization of the central nervous system white matter.
Complete absence of any auricular structures. [HPO:probinson, pmid:19125421]
familial or idiopathic form, usually fatal; Fanconi's anemia presents before age 10, marked by microcephaly, skin discolorations, and sexual and mental retardation.
A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).
Partial or complete absence of the flat bones of the cranial vault. The condition is frequently, though not always, associated with anencephaly.
brand name of carisoprodol, a muscle relaxant drug
Abnormally high level of basophils in the blood.
A combination preparation of acetaminophen, butalbital, and caffeine. Acetaminophen exerts antipyretic and analgesic activities by inhibiting prostaglandin synthesis. Butalbital, a barbiturate with an intermediate duration of action, depresses the central nervous system and exerts sedative activity. Caffeine is a central nervous system stimulant and causes constriction of dilated cerebral blood vessels. This combination is used for the relief and treatment of migraine and tension headaches.
A combination preparation containing pyrilamine, caffeine and acetaminophen. Pyrilamine is an ethylenediamine antihistamine that blocks H1 receptors and exerts local anesthetic, sedative and mild analgesic activities. Caffeine is a central nervous system stimulant. Acetaminophen possesses analgesic and antipyretic effects. This preparation is used for the relief of premenstrual and menstrual symptoms.
A combination preparation containing isometheptane, dichloralphenazone and acetaminophen with analgesic activity. Isometheptene is an indirect-acting sympathomimetic agent with vasoconstricting activity, thereby reducing the pulsation in cerebral arteries by constricting dilated cerebral blood vessels. Dichloralphenazone, a complex of chloral hydrate, which possesses hypnotic and sedative activity, and antipyrine, a pyrazolone analgesic and an antipyretic. Acetaminophen inhibits prostaglandin synthesis, thereby exerting analgesic activity. This preparation is used for the relief of migraine and tension headaches.
A combination preparation containing pyrilamine, pamabron and acetaminophen. Pyrilamine is an ethylenediamine antihistamine that blocks H1 receptors and exerts local anesthetic, sedative and mild analgesic activity. Pamabrom, a xanthine derivate, is a mild diuretic that helps the body to excrete excess fluid. Acetaminophen possesses analgesic and antipyretic effects. This preparation is used for the relief of premenstrual and menstrual symptoms.
Vaccines or candidate vaccines used to prevent LYME DISEASE.
A synthetic p-aminophenol derivative and diphenhydramine combination with anti-inflammatory, analgesic, and anti-allergic properties. Acetaminophen Diphenhydramine is used to treat symptoms of allergies and hay fever. The active principal metabolite of phenacetin, acetaminophen appears to inhibit prostaglandin biosynthesis in the central nervous system and less in peripheral tissues. Diphenhydramine blocks histamine effects, preventing sneezing and itchy, watery eyes, as well as nasal and other allergy and hay fever symptoms. (NCI04)
A combination preparation of the analgesic acetaminophen and the semisynthetic opioid agonist hydrocodone with analgesic and antitussive activities. Acetaminophen exerts its analgesic activity by inhibiting prostaglandin synthesis while hydrocodone exerts its analgesic activity by binding to the mu-receptors in the central nervous system (CNS), thereby mimicking the effects of endogenous opioids.
A combination preparation of the analgesic and antipyretic acetaminophen and the semisynthetic opioid agonist oxycodone with analgesic and antitussive properties. Acetaminophen exerts its analgesic activity by inhibiting prostaglandin synthesis, while oxycodone exerts its analgesic activity by binding to the mu-receptors in the central nervous system (CNS), thereby mimicking the effects of endogenous opioids.
A combination of albuterol and ipratropium with a bronchodilatory effect. Albuterol stimulates beta-2 adrenergic receptors in the lungs, thereby activating the enzyme adenylate cyclase that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'- adenosine monophosphate (cAMP). This results in the relaxation of bronchial smooth muscle, relieve of bronchospasms, and reduction of inflammatory cell mediator release. Ipratropium is a synthetic quaternary ammonium compound and a competitive muscarinic acetylcholine (Ach) receptor antagonist. This agent inhibits vagally mediated reflexes by antagonizing the action of Ach and consequently, prevents the increase in intracellular cyclic guanosine monophosphate, which is a result of ACh interacting with the muscarinic receptor on bronchial smooth muscle.
A combination preparation of the synthetic angiotensin-converting enzyme (ACE) inhibitor prodrug benazepril and the thiazide diuretic hydrochlorothiazide, with antihypertensive activity. Benazepril is de-esterified by the liver into its active form benazeprilat, which competitively inhibits ACE. ACE inhibition prevents the formation of angiotensin II, and blocks angiotensin II-mediated activities, including vasoconstriction and stimulation of synthesis and secretion of aldosterone, which leads to an increase in sodium excretion and increases water outflow. Hydrochlorothiazide inhibits electrolyte reabsorption via binding to the Na-Cl cotransporter on the renal distal tubules, thereby increasing excretion of sodium, potassium, chloride, bicarbonate and water. Together, these agents lead to a reduction in blood pressure.
A calcium salt of acetic acid. Calcium is a mineral essential for many cellular functions including nerve impulse transmission, muscle contraction, cardiac function, bone formation, and capillary and cell membrane permeability. Calcium acetate is administered orally to prevent or treat calcium deficiency and to treat hyperphosphatemia due to its phosphate-binding properties.
A synthetic, benzimidazole-derived angiotensin II receptor antagonist prodrug with antihypertensive activity. Candesartan selectively competes with angiotensin II for the binding of the angiotensin II receptor subtype 1 (AT1) in vascular smooth muscle, blocking angiotensin II-mediated vasoconstriction and inducing vasodilatation. In addition, antagonism of AT1 in the adrenal gland inhibits angiotensin II-stimulated aldosterone synthesis and secretion by the adrenal cortex; sodium and water excretion increase, followed by a reduction in plasma volume and blood pressure.
A combination of laxatives, Casanthranol Docusate is used in constipation and various medical conditions. Casanthranol is a concentrated mixture of anthranol glycosides from cascara sagrada (dried bark of Rhamnus p.) and a stimulant laxative that encourages bowel movements by acting on the intestinal wall to increase muscle contractions. A surface-active emollient, stool softener Docusate helps liquids to mix into dry stool, allowing patients to have a bowel movement without straining. (NCI04)
A combination preparation containing guaifenesin and the opioid agonist codeine with expectorant and antitussive activities, respectively. Guaifenesin works by drawing water into respiratory tracts, by which reducing adhesiveness and surface tension of mucus as well as increasing hydration of mucus, thereby reducing the viscosity of mucus and making cough more productive. Codeine, a naturally occurring phenanthrene alkaloid and opioid agonist mimics the actions of opioids by binding to the opioid receptors at many sites within the central nervous system (CNS), thereby also suppressing the cough reflex by activating receptors in the cough center.
A combination of probenecid and colchicine with antihyperuricemic activity. Probenecid, a benzoic acid derivative, competitively inhibits the reabsorption of urate at the proximal tubule in the kidney, thereby increasing urinary excretion of uric acid and lowering serum urate concentrations. This prevents urate deposition and promotes resolution of existing urate deposits. Colchicine is a natural alkaloid with anti-gout and anti-inflammatory properties. Colchicine binds to tubulin, thereby interfering with the polymerization of tubulin, interrupting microtubule dynamics, and disrupting mitosis leading to an inhibition of leukocyte migration and reduction of the inflammatory response to deposited urate crystals. This agent also interrupts monosodium urate crystal deposition in joint tissues, thereby preventing the resultant inflammatory response.
A cytotoxic recombinant protein consisting of interleukin-2 (IL-2) protein sequences fused to diphtheria toxin. The IL-2 protein sequence moiety of denileukin difitox directs the cytocidal action of diphtheria toxin to cells that express IL-2 receptors. After the toxin moiety is internalized into target IL-2 receptor-expressing cells, its catalytic domain catalyzes the transfer of the ADP-ribose moiety of NAD to a posttranslationally modified histidine residue of elongation factor 2 (EF-2), called diphthamine. This covalent modification inactivates EF-2 and disrupts polypeptide chain elongation, resulting in cell death. (NCI04)
A combination preparation containing guaifenesin and the opioid agonist dextrometorphan with expectorant and antitussive activities, respectively. Guaifenesin works by drawing water into respiratory tracts, by which reducing adhesiveness and surface tension of mucus as well as increasing hydration of mucus, thereby reducing the viscosity of mucus and making cough more productive. Dextrometorphan, a synthetic, methylated dextrorotary analogue of levorphanol, exhibits antitussive activity by activating opioid receptors in the cough center in the central nervous system, thereby raising the threshold for coughing.
A pharmaceutical preparation containing a mixture of esterified estrogens derived from estrogen sulfates, principally from ESTRONE sulfate. Esterified estrogen content should be 75-85% of the estrone sulfate and 6-15% of the EQUILIN sulfate.
A recombinant soluble dimeric fusion protein consisting of the extracellular ligand-binding region of recombinant human tumor necrosis factor (rhTNF) receptor attached to the constant (Fc) region of human immunoglobulin G (FcIgG). The receptor moiety of etanercept binds to circulating TNF (2 molecules of TNF per receptor) and inhibits its attachment to endogenous TNF cell surface receptors, thereby rendering TNF inactive and inhibiting TNF-mediated mechanisms of inflammation. (NCI04)
A combination of two steroid sex hormones, an estrogen and a progestin, used for contraceptive purposes. Estradiol, the endogenous counterpart of ethinyl estradiol (EE), is the principal, most potent estrogen hormone produced by the ovaries and is vital to the maintenance of fertility and secondary sexual characteristics in females. Levonorgestrel is a synthetic progestogen. This drug combination prevents or delays ovulation and causes a variety of hormonal changes. Ethinyl estradiol inhibits the release of follicle stimulating hormone (FSH), thus suppressing the development of ovarian follicle; levonorgestrel inhibits the release of luteinizing hormone (LH), thus preventing ovulation. This combination of agents alters the endometrium in such a way as to discourage implantation. (NCI04)
An oral preparation combination containing the semisynthetic estrogen ethinyl estradiol and the synthetic progestagen norgestimate with contraceptive activity. Ethinyl estradiol and norgestimate act by negative feed back mechanism at pituitary gland suppressing the release of gonadotropin hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH). This combination inhibits ovulation and promotes the thickening of the cervical mucus and the endometrium. The combination of ethinyl estradiol and norgestimate may also be used in the treatment of acne.
A combination of two steroid sex hormones, the semisynthetic estrogen ethinyl estradiol and the synthetic progestogen norgestrel, with contraceptive activity. The combination of ethinyl estradiol with norgestrel suppresses the hypothalamic-pituitary system, leading to an inhibition of the release of follicle stimulating hormone (FSH), thus suppressing the development of ovarian follicles. The release of luteinizing hormone (LH) is also inhibited, thus preventing ovulation. In addition, thickening of the cervical mucus and the endometrium is promoted, thereby altering the endometrium in such a way as to discourage implantation.
synthetic polypeptide consisting of alanine, glutamic acid, lysine, and tyrosine; simulates myelin basic protein and is used experimentally in the treatment of relapsing and remitting multiple sclerosis.
A combination preparation containing guaifenesin and the indirect-acting sympathicomimetic agent pseudoephedrine with expectorant and decongestant activities, respectively. Guaifenesin works by drawing water into respiratory tracts, by which reducing adhesiveness and surface tension of mucus as well as increasing hydration of mucus, thereby reducing the viscosity of mucus and making cough more productive. Pseudoephedrine displaces norepinephrine from storage vesicles in presynaptic neurons, thereby releasing norepinephrine into the neuronal synapses where it stimulates primarily alpha-adrenergic receptors in the nasal mucosa, thereby producing vasoconstriction, reduces swelling of nasal mucous membranes and decreasing nasal and sinus congestion.
A vaccine against serotype b of the Gram-negative bacterium H. influenzae (Hib). Hib vaccines contain polysaccharide-protein conjugate antigens that produce greater host immune responses than first-generation purified polysaccharide vaccine. These vaccines may differ with regard to use of protein carriers, polysaccharides, diluents, and preservatives.
A combination preparation of a synthetic angiotensin II antagonist and a diuretic thiazide, with antihypertensive activity. Losartan, and its metabolite, selectively and competitively block the binding of angiotensin II to the angiotensin II (AT1) receptor. As a result, angiotensin II-AT1 mediated physiological effects such as vasoconstriction and stimulation of aldosterone synthesis and secretion, which regulates extracellular sodium concentration, are blocked. Hydrochlorothiazide inhibits electrolytes reabsorption via binding to Na-Cl cotransporter on the renal distal tubular, thereby increasing excretion of sodium, potassium, chloride, bicarbonate and water. Both agents lead to a reduction in blood pressure.
A combination of two synthetic nucleoside analogues with synergistic antiviral properties. Lamivudine is phosphorylated intracellularly to its active 5'-triphosphate metabolite, lamivudine triphosphate (L-TP); zidovudine is phosphorylated to its active 5'-triphosphate metabolite, zidovudine triphosphate (ZDV-TP). These active metabolites inhibit human immunodeficiency virus (HIV) viral reverse transcriptase (RT) by incorporating into viral DNA and terminating viral DNA chain elongation. (NCI04)
An oral combination preparation containing the antihistamine loratidine and the indirect-acting sympathicomimetic agent pseudoephedrine, with anti-allergic and decongestant activities. Loratadine, a piperidine, blocks the H1-receptor thereby preventing the symptoms that are caused by histamine activity on capillaries, bronchial smooth muscle, and gastrointestinal smooth muscle, including vasodilatation, increased capillary permeability, bronchoconstriction, and spasmodic contraction of gastrointestinal smooth muscle. Pseudoephedrine displaces norepinephrine from storage vesicles in presynaptic neurons, thereby releasing norepinephrine into the neuronal synapses where it stimulates primarily alpha-adrenergic receptors in the nasal mucosa, thereby producing vasoconstriction, reduces swelling of nasal tissues and decreasing nasal and sinus congestion.
A suspension of formalin-inactivated poliovirus grown in monkey kidney cell tissue culture and used to prevent POLIOMYELITIS.
A combination preparation containing potassium phosphate and sodium phosphate used for electrolyte-replacement purposes, dietary supplementation and to acidify urine. Phosphate, a predominant intracellular anion, plays an important role in energy storage, osteoblastic and osteoclastic activities, regulating serum calcium concentrations and numerous cellular phosphate-transfer reactions. Potassium phosphate and sodium phosphate are used to acidify the urine and lower the urinary calcium concentration. This may reduce rash and odor caused by ammonium in the urine.
A non-absorbable polymeric amine and phosphate binding agent that can be used to prevent hyperphosphatemia. Upon oral administration, the amine groups in sevelamer become protonated in the intestines and bind to the dietary phosphate groups in the gastrointestinal (GI) tract, thereby preventing the absorption of phosphate and controlling phosphate plasma levels. In addition, sevelamer, as a phosphate binder, can be used to prevent the absorption of the radionuclide phosphorus P 32 (P-32).
The sodium salt of phenylbutyrate, a derivative of the short-chain fatty acid butyrate, with potential antineoplastic activity. Phenylbutyrate reversibly inhibits class I and II histone deacetylases (HDACs), which may result in a global increase in gene expression, decreased cellular proliferation, increased cell differentiation, and the induction of apoptosis in susceptible tumor cell populations.
A topical solution containing the caustic agent trichloroacetic acid (TCA), with potential keratolytic, anti-viral and antineoplastic activities. Upon topical application to the affected area, TCA causes tissue necrosis through coagulation of proteins, leads to the destruction of human papilloma virus (HPV)-associated warts and inhibits HPV-driven proliferation of cancer cells.
brand name of a medication that is used to treat vaginal yeast infections
A combination preparation of propoxyphene napsylate and acetaminophen, with analgesic and antipyretic activities. Propoxyphene napsylate is a mild narcotic analgesic that binds to mu-opioid receptors in the central nervous system (CNS), thereby mimicking the effect of endogenous opioids. Acetaminophen possesses analgesic and antipyretic effects by interfering with prostaglandin synthesis.
An organic salt of ammonium (lactic acid neutralized with ammonium hydroxide), topical moisturizing Ammonium Lactate can be applied as a humectant in ichthyosis vulgaris and xerosis. Available as cream or lotion, this agent moisturizes the skin and breaks up the scales. (NCI04)
Used to relieve stomach/intestinal symptoms, menopause (hot flashes, sweats, restlessness, and insomnia), headaches, and tachycardia, Belladona Phenobarbital Ergotamine is a combination of an Atropa belladonna alkaloid, a Claviceps purpurea (Ergotamine) alkaloid, and a synthetic barbiturate. Parasympathomimetic Belladona decreases secretion, smooth muscle stimulant Ergotamine blocks alpha-adrenergic activity, and sedative Phenobarbital induces sleep. (NCI04)
A combination preparation containing the belladonna alkaloids atropine sulfate, hyoscyamine sulfate, and scopolamine hydrobromide, and the barbiturate phenobarbital with antispasmodic, anxiolytic and sedative activities. The belladonna alkaloids bind to and block muscarinic receptors in the gastrointestinal (GI) tract. This leads to a decrease in stomach secretions, GI motility and GI spasms. Phenobarbital binds to a distinct site on the gamma-aminobutyric acid (GABA)-A subtype receptor in the central nervous system (CNS), thereby increasing the influx of chloride ions into the neuron and potentiating GABA-induced increases in chloride conductance. This enhances postsynaptic responses to the inhibitory actions of GABA and causes CNS depression.
A nonsteroidal anti-inflammatory drug (NSAID) belonging to the salicylate family. Choline magnesium trisalicylate inhibits inflammation-related prostaglandin synthesis. This agent's analgesic effect is mediated through peripheral and central pathways, resulting in a decrease in pain perception; its antipyretic effect is mediated via the hypothalamic heat regulation center. (NCI04)
A daytime non-drowsy preparation used to relieve common cold and flu symptoms. Dextromethorphan, one of the active ingredients, exerts its activity by raising the threshold for coughing in the cough center. Another ingredient of Dayquil, phenylephrine, a post-synaptic alpha-adrenergic receptor agonist, induces vasoconstriction, and thereby reduces blood flow, decreases swelling and prevents nasal and sinus congestion.
brand name of a high blood pressure medication
brand name of a drug that is used to treat rheumatism
A commercial preparation, by Novartis, with laxative activity. Ex-Lax contains anthraquinone glycosides sennosides, extracted from senna leaves. Sennosides irritate the lining of the intestine wall, thereby causing increased intestinal muscle contractions that lead to vigorous bowel movement and relief constipation.
brand name of anti-inflammatory eye drops
The hydrochloride salt of methadone, a synthetic opioid with analgesic activity. Similar to morphine and other morphine-like agents, methadone mimics the actions of endogenous peptides at CNS opioid receptors, primarily the mu-receptor, resulting in characteristic morphine-like effects including analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia and physical dependence. Because of the prolonged half-life of methadone compared to other morphine-like agents such as heroin, the onset of opiate withdrawal symptoms is slower, the duration of opiate withdrawal is prolonged, and opiate withdrawal symptoms are less severe.
A dietary supplement containing all or most of the vitamins and some minerals which may not be readily available in the diet. The vitamin component may be classified according to their solubility either in lipids (vitamins A, D, E, K, F) or in water (vitamins C, B- complex). Present in minute amounts in various foods, vitamins are essential to maintaining normal metabolism and biochemical functions. The mineral component contains essential microelements and metals such as iron, magnesium, chromium and iodine. In addition, these agents may include various anti-oxidant phytochemicals such as flavonoids. (NCI04)
brand name of an estrogen replacement drug
An iron supplement consisting of an iron atom bound by a polysaccharide molecule.
brand name of infliximab a drug used to treat autoimmune disorders
A commercial combination preparation, by Purdue, containing a standardized senna concentrate and docusate sodium with laxative and stool softening activity. Senna concentrate consists of the anthraquinone glycosides sennosides extracted from senna leaves. Sennosides act on and irritate the lining of the intestine wall, thereby causing increased intestinal muscle contractions leading to vigorous bowel movement and relief of constipation. Docusate sodium, an anionic surfactant, softens the stool for smoother and easier evacuation.
A sodium salt form of sulfadiazine, an intermediate-acting bacteriostatic, synthetic sulfanilamide derivative.
brand name of a drug that is used to dissolve gallstones
A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.
A sulfate salt form of abacavir, a nucleoside reverse transcriptase inhibitor analog of guanosine. This agent decreases HIV viral loads, retards or prevents the damage to the immune system, and reduces the risk of developing AIDS.
The aspartate salt of amphetamine, a sympathomimetic amine with CNS stimulating properties. Amphetamine acts by facilitating the release of catecholamines, particularly noradrenaline and dopamine, from nerve terminals in the brain and inhibiting their uptake. Physiological effects include an increase in motor activity, euphoria, increased mental alertness, excitatory behavior, and appetite suppression.
The sodium salt of cerivastatin, a synthetic lipid-lowering agent.
The orally bioavailable hydrobromide salt of the racemic bicyclic phthalene derivative citalopram with antidepressant activity. As a selective serotonin reuptake inhibitor (SSRI), citalopram selectively inhibits the CNS neuronal reuptake of serotonin, thereby potentiating serotonergic activity in the central nervous system (CNS). This agent has minimal effects on the CNS neuronal reuptake of norepinephrine (NE) and dopamine (DA).
A tricarboxylic acid found in citrus fruits. Citric acid is used as an excipient in pharmaceutical preparations due to its antioxidant properties. It maintains stability of active ingredients and is used as a preservative. It is also used as an acidulant to control pH and acts as an anticoagulant by chelating calcium in blood.
A preparation used in cleaning something.
The saccharate salt form of the dextro-isomer of amphetamine, a synthetic substance related to natural sympathomimetic amines, with CNS stimulating properties. Dextroamphetamine saccharate acts by facilitating the release of catecholamines, particularly noradrenaline and dopamine, from its storage sites in nerve terminals in the brain, and inhibits their uptake within the mesocorticolimbic system, a major component of the brain reward system, thereby resulting in measurable behavioral changes such as euphoria. As a CNS stimulant, this agent may increase blood pressure and reduce appetite. Similar to other amphetamines, dextroamphetamine has a high potential for abuse, dependence, and addiction if used in large doses over extended periods of time.
The difumarate salt form of emedastine, a second generation, selective histamine H1 receptor antagonist with anti-allergic activity. Emedastine reversibly and competitively blocks histamine by binding to H1 receptors, thus blocking its downstream activity. As a result, this agent interferes with mediator release from mast cells either by inhibiting calcium ion influx across mast cell/basophil plasma membrane or by inhibiting intracellular calcium ion release within the cells. In addition, emedastine may also inhibit the late-phase allergic reaction mediated through leukotrienes or prostaglandins, or by producing an anti-platelet activating factor effect. Upon ocular administration, emedastine causes a dose-dependent inhibition of histamine-stimulated vascular permeability in the conjunctiva. Emedastine does not affect adrenergic, dopamine, or serotonin receptors.
Coagulation factor IX (461 aa, ~52 kDa) is encoded by the human F9 gene. This protein plays a role in the intrinsic pathway of blood coagulation through the mediation of proteolysis that converts factor X into an active protease.
The acetate salt form of fluorometholone, a synthetic glucocorticoid with anti-inflammatory and anti-allergic properties. Fluorometholone acetate exerts its effect by interacting with cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. The synthesis of certain anti-inflammatory proteins is induced while the synthesis of certain inflammatory mediators is inhibited. As a result, there is an overall reduction in chronic inflammation and autoimmune reactions.
A therapeutic glycoprotein hormone synthesized by recombinant DNA technology or purified from biological sources, whose endogenous counterpart follicle stimulating hormone (FSH) stimulates and maintains the normal functions of reproductive system in males and females. (NCI04)
The acetate salt form of histrelin, a long-acting, synthetic nonapeptide analog of gonadotropin-releasing hormone (GnRH) with potential anti-tumor activity. Upon administration, histrelin binds to and activates GnRH receptors; prolonged administration results in pituitary GnRH receptor desensitization and inhibition of follicle stimulating hormone (FSH) and luteinizing hormone (LH) secretion, leading to a significant decline in testosterone production in males and may inhibit androgen receptor-positive tumor progression; in females, prolonged administration results in decreased estradiol production.
Regular insulin preparations that contain the SUS SCROFA insulin peptide sequence.
The succinate salt form of metoprolol, a cardioselective competitive beta-1 adrenergic receptor antagonist with antihypertensive properties and devoid of intrinsic sympathomimetic activity. Metoprolol succinate antagonizes beta 1-adrenergic receptors in the myocardium, thereby reducing the rate and force of myocardial contraction, and consequently a diminished cardiac output. This agent may also reduce the secretion of renin with subsequent reduction in levels of angiotensin II thus decreasing sympathetic activation, including vasoconstriction, aldosterone secretion.
The hydrochloride salt form of moricizine, a phenothiazine analog with class I antiarrhythmic activity. Moricizine hydrochloride blocks the rapid flow of sodium ions into the myocardial cell during phase 0 of the action potential. This decreases excitability, slows the impulse conduction through the atrioventricular (AV) node and depresses depolarization.
The acetate salt of a synthetic long-acting cyclic octapeptide with pharmacologic properties mimicking those of the natural hormone somatostatin. Octreotide is a more potent inhibitor of growth hormone, glucagon, and insulin than somatostatin. Similar to somatostatin, this agent also suppresses the luteinizing hormone response to gonadotropin-releasing hormone, decreases splanchnic blood flow, and inhibits the release of serotonin, gastrin, vasoactive intestinal peptide (VIP), secretin, motilin, pancreatic polypeptide, and thyroid stimulating hormone.
Also known as Laudanum and formulated for oral administration, Opium tincture is made of air-dried poppy (Papaver somniferum) latex and contains alkaloids such as morphine and codeine. As an antidiarrheal agent, it slows transit of intestinal contents by increasing intestinal smooth muscle tone and inhibiting motility; water is absorbed from fecal contents, decreasing diarrhea. (NCI04)
The acetate salt form of pirbuterol, a synthetic catecholamine and a pyridine derivative with sympathomimetic and bronchodilatory effects. Pirbuterol acetate selectively stimulates beta-2 adrenergic receptors, resulting in initiation of intracellular adenylate cyclase activity leading to increased levels of cAMP. As a result muscle relaxation (broncho- and vasodilation) occurs via cAMP-dependent signal transduction. In addition, elevated levels of cAMP inhibit release of inflammatory mediators from mast cells.
A dibenzothiazepine and ANTIPSYCHOTIC AGENT that targets the SEROTONIN 5-HT2 RECEPTOR; HISTAMINE H1 RECEPTOR, adrenergic alpha1 and alpha2 receptors, as well as the DOPAMINE D1 RECEPTOR and DOPAMINE D2 RECEPTOR. It is used in the treatment of SCHIZOPHRENIA; BIPOLAR DISORDER and DEPRESSIVE DISORDER.
A PHOSPHODIESTERASE TYPE-5 INHIBITOR; VASODILATOR AGENT and UROLOGICAL AGENT that is used in the treatment of ERECTILE DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION.
The sodium salt form of tazobactam, a penicillanic acid sulfone derivative and beta-lactamase inhibitor with antibacterial activity. Tazobactam contains a beta-lactam ring and irreversibly binds to beta-lactamase at or near its active site. This protects other beta-lactam antibiotics from beta-lactamase catalysis. This drug is used in conjunction with beta-lactamase susceptible penicillins to treat infections caused by beta-lactamase producing organisms.
A cationic surface-active compound. As an additive to pharmacologic formulations, thonzonium bromide causes dispersion and penetration of cellular debris and exudate, thereby promoting tissue contact of the administered medication.
The sodium salt form of tolbutamide, a short-acting, first-generation sulfonylurea with hypoglycemic activity. Compared to second-generation sulfonylureas, tolbutamide is more likely to cause adverse effects, such as jaundice. This agent is rapidly metabolized by CYPC29.
An ANTIMUSCARINIC AGENT selective for the MUSCARINIC RECEPTORS of the BLADDER that is used in the treatment of URINARY INCONTINENCE and URINARY URGE INCONTINENCE.
The sulfate salt form of trimethoprim, a synthetic substituted pyrimidine with antibacterial activity. Trimethoprim sulfate selectively binds to and reversibly inhibits dihydrofolate reductase, thereby blocking the production of tetrahydrofolic acid from dihydrofolic acid. This leads to an inhibition of bacterial synthesis of folic acid, thereby affecting nucleic acid and protein synthesis. Trimethoprim sulfate has a stronger binding affinity for the bacterial enzyme than for the corresponding mammalian enzyme.
The tartrate salt of an imidazopyridine with non-benzodiazepine benzodiazepine-receptor agonist and sedative-hypnotic activities. Zolpidem binds selectively to the alpha 1 subunit of the omega-1 (BZ1) receptor of the gamma-aminobutyric acid type A (GABA-A) receptor-chloride ionophore complex, thereby opening neuronal chloride channels, hyperpolarizing neuronal cell membranes, and inhibiting neuronal firing. In contrast, benzodiazepines non-selectively bind to and activate all omega receptor subtypes, exhibiting anticonvulsant and myorelaxant activities in addition to a sedative-hypnotic activity.
A type of orange tree grown in Italy. The essential oil from the peel of this orange is used in perfume, to get rid of insects, and to flavor tea. Bergamot oil is also used in aromatherapy for depression, anxiety, and poor digestion. The scientific name for the bergamot orange tree is Citrus bergamia.
A low viscosity liquid by-product of the distillation of petroleum consisting of a mixture of alkanes in the C15 to C40 range. Light mineral oil has uses in biotechnology, pharmaceutics, cosmetics, and industry.
Fetus with birthweight of 1000-2499 grams AND/OR gestation of 28-37 weeks
A humanized monoclonal antibody against the ERBB-2 RECEPTOR (HER2). As an ANTINEOPLASTIC AGENT, it is used to treat BREAST CANCER where HER2 is overexpressed.
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.
A malignant neoplasm affecting the nasal cavity. Representative examples include carcinoma and lymphoma.
A developmental defect resulting in the presence of fewer than the normal number of fingers.
Disturbances in psychophysiological functions and responses as a result of administration or ingestion of a psychoactive substance.
A malignant epithelial neoplasm arising from the appendix. The vast majority of the cases are adenocarcinomas.
An abnormally decreased concentration of parathyroid hormone. [PMID:1302009, RGD:gthayman]
complex, lipid-soluble, macrocyclic lactone produced by the Japanese soil bacterium Streptomyces tsukubaensis; experimental immunosuppressant which inhibits T-lymphocyte activation and fungal growth by binding to peptidyl prolyl isomerase, forming a complex which interferes with calcium signaling.
A dissecting aneurysm formed between the intimal and medial layers of the wall of the proximal portion of the descending aorta proceeding from the arch of the aorta.
Preterm premature rupture of the membranes is defined as rupture of membranes before 37 weeks of gestation, which occurs in approximately 3% of all pregnancies and accounts for about one-third of spontaneous preterm births (ACOG Practice Bulletin, 1998). Srinivas and Macones (2005) reviewed the pathophysiology of PPROM and noted that familial clustering and ethnic differences in the incidence of PPROM suggest possible genetic influences.
Defective bone growth that affects the growth centers of bone in children.
MYCOSES of the brain, spinal cord, and meninges which may result in ENCEPHALITIS; MENINGITIS, FUNGAL; MYELITIS; BRAIN ABSCESS; and EPIDURAL ABSCESS. Certain types of fungi may produce disease in immunologically normal hosts, while others are classified as opportunistic pathogens, causing illness primarily in immunocompromised individuals (e.g., ACQUIRED IMMUNODEFICIENCY SYNDROME).
An acute or chronic infectious process affecting the mediastinum.
A viral, bacterial, fungal, or parasitic infectious process that affects the digestive system.
Floating-Harbor syndrome (FHS) is characterized by typical craniofacial features; low birth weight, normal head circumference, and short stature; bone age delay that normalizes between ages six and 12 years; skeletal anomalies (brachydactyly, clubbing, clinodactyly, short thumbs, prominent joints, clavicular abnormalities); severe receptive and expressive language impairment; hypernasality and high-pitched voice; and intellectual disability that is typically mild to moderate. Difficulties with temperament and behavior that are present in many children tend to improve in adulthood. Other features can include: hyperopia and/or strabismus; conductive hearing loss; seizures; gastroesophageal reflux; renal anomalies (e.g., hydronephrosis/renal pelviectasis, cysts, and/or agenesis) and genital anomalies (e.g., hypospadias and/or undescended testes).
Inflammation of the meninges of the brain and/or spinal cord caused by an infectious agent (viral, bacterial, or fungal). Symptoms include headache, fever, vomiting, neck stiffness, photophobia, confusion, and seizures.
A viral or bacterial infectious process affecting the cornea. Symptoms include pain and redness in the eye, photophobia and eye watering.
A neoplasm that arises from the glandular epithelium of the rectal mucosa. It is characterized by a villous architectural pattern. The neoplastic glandular cells have dysplastic features.
The following must be present on at least one OCT (Optical coherence tomography ) scan image: (i) Partial vitreous detachment as indicated by elevation of cortical vitreous above the retinal surface in the perifoveal area (ii) Persistent vitreous attachment.
A general term which describes a group of rare eye disorders that affect the cone cells of the RETINA. Cone dystrophy can cause a variety of symptoms including decreased visual clarity or acuity when looking straight ahead (central vision), a reduced ability to see colors, and an increased sensitivity to light (PHOTOPOBIA).
Macular dystrophy is a nonspecific term for premature retinal cell aging and cell death, generally confied to the macula in which no clear extrinsic cause is evident.
North Carolina macular dystrophy (NCMD, MCDR1) is a congenital autosomal dominant trait that appears to be completely penetrant. It is generally nonprogressive. The ophthalmoscopic findings are highly variable and are always much more dramatic than one would predict from the relatively good visual acuity level, which ranges from 20/20 to 20/400 (median, 20/60). Patients may have only a few drusen in the central macular region (grade I), confluent drusen confined to the central macular region (grade II), or a severe macular coloboma/staphyloma (grade III) involving 3 to 4 disc areas of the central macular region. Choroidal neovascular membranes develop in some patients. Color vision is normal. Electrophysiologic studies are also normal (summary by Small, 1998). Genetic Heterogeneity of Retinal Macular Dystrophy MCDR2 (608051) is caused by mutation in the PROM1 gene (604365) on chromosome 4p15, and MCDR3 (608850) has been mapped to chromosome 5p15-p13. See MAPPING for possible additional loci for MCDR.
Acute zonal occult outer retinopathy (AZOOR) is typified by acute loss of 1 or more zones of outer retinal function associated with photopsia, minimal funduscopic changes, and abnormal ERG findings
A benign vascular tumor of the retina without any neoplastic characteristics. [HPO:probinson]
A benign tumor of the retina that appears as a grouping of blood-filled saccules within the inner retinal layers or on the surface of the optic disc. Retinal cavernous angioma are described as having a 'cluster of grapes' appearance.
An anomaly of the retina with serous detachment of the neurosensory retina secondary to one or more focal lesions of the retinal pigment epithelium (RPE), and associated with blurred vision, usually in one eye only and perceived typically by the patient as a dark spot in the centre of the visual field with associated micropsia and metamorphopsia. Normal vision often recurs spontaneously within a few months. [PMID:17662099]
The presence of mildly increased concentrations of albumin in the urine (in adults, 30-150 mg per day). [Eurenomics:fschaefer]
A structural abnormality of the macula lutea, which is an oval-shaped highly pigmented yellow spot near the center of the retina.
An intermittent esotropia where there is binocular single vision on distance fixation and esotropia at near even when the accommodation is relieved. [ORCID:0000-0003-0986-4123]
An intermittent esotropia where binocular single vision is present on near fixation and an esotropia on distance fixation. Often associated with myopia and aging. [UManchester:psergouniotis]
Convergent strabismus in which normal binocular single vision is alternating with large angle esotropia in rhythmic cycle. [ORCID:0000-0003-0986-4123]
The false appearance of misalignment of the eyes.
A type of divergent strabismus (exotropia) in which an eye tends to turn outwards (i.e., the eye squints) mainly when looking at distant objects. The eyes tend to remain straight when they look at near objects. Distance exotropia may be constant or intermittant. [ORCID:0000-0003-0986-4123]
An intermittent exotropia where there is binocular single vision on distance fixation and exotropia at near (intermittent or constant). [ORCID:0000-0003-0986-4123]
Hydromorphone hydrochloride extended release.
An active metabolite of folic acid (also called folinic acid and citrovorum factor), which does not require metabolism by dihydrofolate reductase, the molecular target of folate antagonist-type chemotherapeutic drugs. Leucovorin calcium counteracts the toxic effects of these medications, 'rescuing' the patient while permitting the antitumor activity of the folate antagonist. This agent also potentiates the effects of fluorouracil and its derivatives by stabilizing the binding of the drug's metabolite to its target enzyme, thus prolonging drug activity. (NCI04)
A drug combination of aspirin and dipyridamole that functions as a PLATELET AGGREGATION INHIBITOR, used to prevent THROMBOSIS and STROKE in TRANSIENT ISCHEMIC ATTACK patients.
The sodium salt of the prodrug rabeprazole, a substituted benzimidazole proton pump inhibitor, with potential anti-ulcer activity. After protonation, accumulation, and transformation to the active sulfenamide within the acidic environment of gastric parietal cells, rabeprazole selectively and irreversibly binds to and inhibits the H+, K+ATPase (hydrogen-potassium adenosine triphosphatase) enzyme system located on the parietal cell secretory surface, inhibiting gastric acid secretion.
A structurally diverse group of compounds distinguished from ESTROGENS by their ability to bind and activate ESTROGEN RECEPTORS but act as either an agonist or antagonist depending on the tissue type and hormonal milieu. They are classified as either first generation because they demonstrate estrogen agonist properties in the ENDOMETRIUM or second generation based on their patterns of tissue specificity. (Horm Res 1997;48:155-63)
A term used in Russian literature for BHT that has no relationship to IONONES.
The hydrochloride salt form of levobunolol, a naphthalenone and non-cardioselective adrenergic beta-receptor antagonist with anti-glaucoma activity. Upon administration in the eye, levobunolol blocks beta-adrenergic receptors, thereby causing vasoconstriction. Levobunolol also decreases ciliary's body production of aqueous humor, leading to a decrease in aqueous humor.
The hydrochloride salt form of fluoxetine, a diphenhydramine derivative and selective serotonin reuptake inhibitor with antidepressant, antiobsessional and antibulimic effects. Fluoxetine binds to the presynaptic serotonin receptor resulting in negative allosteric modulation of the receptor complex, thereby blocking recycling of serotonin by the presynaptic receptor. Inhibition of serotonin reuptake by fluoxetine enhances serotonergic function through serotonin accumulation in the synaptic space, resulting in long-term desensitization and downregulation of 5HT1 (serotonin) receptors leading to antidepressant, antiobsessional and antibulimic effects via various nerve pathways in the brain.
The orally bioavailable, acetate salt form of guanabenz, a centrally-acting alpha-2 adrenergic receptor agonist, with anti-hypertensive and potential antineoplastic, cytoprotective and bone resorption inhibitory activities. Upon oral administration, guanabenz suppresses endoplasmic reticulum (ER) stress by inhibiting the stress-induced dephosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2a), thereby enhancing the phosphorylation level of eIF2a. This causes elF2a-mediated downregulation of the Rac1 pathway, upregulates the expression of activating transcription factor 4 (ATF4), which plays a key role in osteoblastogenesis, and downregulates the expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), which is a transcription factor that plays a key role in osteoclastogenesis. This enhances osteoblastogenesis and suppresses osteoclastogenesis. Altogether, this promotes new bone formation and prevents bone degradation. In addition, guanabenz blocks the proliferation, survival, motility and invasiveness of tumor cells through the eIF2a-mediated downregulation of Rac1 signaling. Rac1, a Ras-related small GTPase belonging to the Rho family, plays a key role in tumor cell proliferation, survival and motility.
The hydrochloride salt of the synthetic imidazothiazole derivative levamisole with anthelminthic and immunomodulating activities. In immunosuppressed states, levamisole may restore immune function by: 1) stimulating antibody formation, 2) stimulating T-cell activation and proliferation, 3) potentiating monocyte and macrophage phagocytosis and chemotaxis and 4) increasing neutrophil mobility, adherence, and chemotaxis.
The hydrochloride salt form of midodrine, a direct-acting prodrug and sympathomimetic agent with antihypotensive properties. Midodrine is converted to its active metabolite, desglymidodrine by deglycination reaction. Desglymidodrine selectively binds to and activates alpha-1-adrenergic receptors of the arteriolar and venous vasculature. This causes smooth muscle contraction and leads to an elevation of blood pressure. Desglymidodrine diffuses poorly across the blood-brain barrier, and is therefore not associated with effects on the central nervous system.
A naturally occurring antioxidant dicatechol originally derived from the creosote bush Larrea divaricatta with antipromoter, anti-inflammatory, and antineoplastic activities. Masoprocol directly inhibits activation of two receptor tyrosine kinases (RTKs), the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu receptor, resulting in decreased proliferation of susceptible tumor cell populations. This agent may induce apoptosis in susceptible tumor cell populations as a result of disruption of the actin cytoskeleton in association with the activation of stress activated protein kinases (SAPKs). In addition, masoprocol inhibits arachidonic acid 5-lipoxygenase (5LOX), resulting in diminished synthesis of inflammatory mediators such as prostaglandins and leukotrienes. It may prevent leukocyte infiltration into tissues and the release of reactive oxygen species.
The mesylate salt of a synthetic imidazoline with alpha-adrenergic antagonist activity. As a competitive alpha-adrenergic antagonist, phentolamine binds to alpha-1 and alpha-2 receptors, resulting in a decrease in peripheral vascular resistance and vasodilatation. This agent also may block 5-hydroxytryptamine (5-HT) receptors and stimulate release of histamine from mast cells.
The sodium salt of fosinopril, a phosphinic acid-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Fosinopril sodium is an ester prodrug that is hydrolysed by esterases to its active metabolite fosinoprilat. Fosinoprilat specifically and competitively inhibits angiotensin-converting enzyme thereby decreasing the formation of the potent vasoconstrictor angiotensin II, resulting in diminished vasopressor activity. In addition, angiotensin II-mediated aldosterone secretion by adrenal cortex is decreased, which results in a decrease of sodium retention and an increase of serum potassium. (NCI05)
Human interferons have been classified into 3 groups: alpha, beta, and gamma. Both alpha- and beta-IFNs, previously designated type I, are acid-stable, but they differ immunologically and in regard to some biologic and physiochemical properties. The IFNs produced by virus-stimulated leukocytes (leukocyte IFNs) are predominantly of the alpha type. Those produced by lymphoblastoid cells are about 90% alpha and 10% beta. Induced fibroblasts produce mainly or exclusively the beta type. The alpha- and beta-IFNs differ widely in amino acid sequence. The gamma or immune IFNs, which are produced by T lymphocytes in response to mitogens or to antigens to which they are sensitized, are acid-labile and serologically distinct from alpha- and beta-IFNs. (from OMIM 147570)
A non-recombinant from of Interferon-beta.
The phenotypic spectrum of X-linked hypophosphatemia (XLH) ranges from isolated hypophosphatemia to severe lower-extremity bowing. XLH frequently manifests in the first two years of life when lower-extremity bowing becomes evident with the onset of weight bearing; however, it sometimes is not manifest until adulthood, as previously unevaluated short stature. In adults, enthesopathy (calcification of the tendons, ligaments, and joint capsules) associated with joint pain and impaired mobility may be the initial presenting complaint. Persons with XLH are prone to spontaneous dental abscesses; sensorineural hearing loss has also been reported.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
brand name of a strong anti-inflammatory drug
A carcinoma of the larynx that arises from the glottic area.
The hydrochloride salt form of proparacaine, a benzoic acid derivative with local anesthetic property. Proparacaine hydrochloride stabilizes the neuronal membrane by binding to and inhibiting voltage-gated sodium channels, thereby inhibiting sodium ion influx required for the initiation and conduction of impulses within the neuronal cell, and resulting in a loss of sensation.
A malignant tumor arising from the epithelium of the intrahepatic or extrahepatic bile duct. Carcinomas that arise from the intrahepatic bile ducts and the hepatic ducts are called cholangiocarcinomas and are almost always adenocarcinomas. Carcinomas that arise from the extrahepatic bile ducts are adenocarcinomas, adenosquamous carcinomas, squamous cell carcinomas, small cell carcinomas, or mucoepidermoid carcinomas.
Atrophy (wasting) of the cerebellum. [HPO:probinson, pmid:12169461]
The 5q- syndrome is a myelodysplastic syndrome characterized by a defect in erythroid differentiation. Patients have severe macrocytic anemia, normal or elevated platelet counts, normal or reduced neutrophil counts, erythroid hypoplasia in the bone marrow, and hypolobated micromegakaryocytes (Ebert et al., 2008).
Abnormal results from the diagnostic tests resulting from cardiac catheterization.
Carcinoma, predominantly squamous cell, arising from epithelial cells of the larynx or pharynx.
An autosomal dominant inherited form of amyloidosis.
An undifferentiated pleomorphic sarcoma that has spread to other anatomical sites.
A non-Hodgkin or Hodgkin lymphoma that arises from any part of the digestive system, with the bulk of the disease localized to that site.
The trapping of bowel or omentum inside the inguinal canal that cannot be reduced, resulting in inflammation, pain, nausea, and possible bowel obstruction.
NECROSIS occurring in the MIDDLE CEREBRAL ARTERY distribution system which brings blood to the entire lateral aspects of each CEREBRAL HEMISPHERE. Clinical signs include impaired cognition; APHASIA; AGRAPHIA; weak and numbness in the face and arms, contralaterally or bilaterally depending on the infarction.
An abnormally high level of uric acid in the blood.
Encephalitis that is associated with systemic lupus erythematosus.
Menopause that is induced by the surgical removal of the ovaries.
Primary or metastatic malignant neoplasm involving the kidney.
A rare, high-grade pleomorphic malignant neoplasm arising from the bone. It usually presents with pain which may or may not be associated with swelling in the affected area. It is characterized by the presence of spindle-shaped cells, polygonal or epithelioid cells, multinucleated giant cells, and inflammatory cells. The neoplastic cells exhibit nuclear pleomorphism and high mitotic activity. It metastasizes frequently, most often in the lungs.
Benign and malignant neoplasms of the cerebellum that arise from astrocytes. During childhood the majority are benign pilocytic astrocytomas. In adults both benign and relatively higher grade forms may occur. The most common presenting symptoms are headache, nausea, vomiting, ataxia of gait or limb, paresis, diplopia, and dizziness. Objective signs include weakness, long tract signs, dysmetria, gait ataxia, papilledema, and nystagmus. Surgical resection is often curative.
A carcinoma that arises from the maxillary sinus. Representative examples include squamous cell carcinoma, adenocarcinoma, and adenoid cystic carcinoma.
Acute inflammation of the lung parenchyma caused by viruses, bacteria, fungi, radiation treatment, or exposure to chemicals. Signs and symptoms include cough, shortness of breath, fevers, chills, chest pain, headache, sweating, and weakness.
Increased resistance to the passage of air in the upper airway.
Maladaptive pattern of drug or alcohol use that may lead to social, occupational, psychological, or physical problems.
Angina pectoris which does not have associated classical symptoms of chest pain. Symptoms may include weakness, nausea, or sweating.
A ruptured aneurysm located in the wall of the aorta.
Asthmatic attacks requiring supplemental corticosteroids.
The condition of being irregular or not conforming to type.
Inflammation of the cartilage of the external ear.
Increased concentration of total (conjugated and unconjugated) bilirubin in the blood.
Hyperplasia of the epithelial cells in the breast ducts. It includes the atypical ductal hyperplasia, papillary intraductal hyperplasia, intraductal myoepitheliosis, and ductal hyperplasia of the usual type.
An increased susceptibility to bronchitis as manifested by a history of recurrent bronchitis.
Cardiovascular Pathology; a subdiscipline of pathology focusing on diseases of the heart or circulatory system.
In response to carotid sinus baroreceptor stimulation, a ventricular pause lasting greater than 3 seconds and/or a fall in systolic BP of greater than 50 mmHg.
A laboratory test result indicating the presence of an increased level of the tumor-associated antigen (TAA) CEA in a biological sample.
Wasting (atrophy) of the vermis of cerebellum.
A benign or malignant solid pathologic process involving the brain and/or the meninges.
A benign neoplasm that arises from the cervix. It is associated with human papillomavirus infection and is characterized by the presence of papillary structures with fibrovascular cores. The papillary structures are covered with stratified squamous epithelium. Koilocytosis is usually present.
Atrophy of the cervical segment of the spinal cord.
A vaso-occlusive crisis of the pulmonary vasculature occurring in patients with sickle cell disease. It is characterized by the presence of a new radiodensity on a chest radiograph accompanied by fever, cough, sputum production, dyspnea, or hypoxia.
A non-Hodgkin or Hodgkin lymphoma that arises in the brain or spinal cord as a primary lesion. There is no evidence of lymphoma outside the central nervous system at the time of diagnosis.
A serrated polypoid lesion that arises in the colon. It is usually found in the distant colon and it rarely produces symptoms. This group includes goblet cell rich, mucin poor, and microvesicular hyperplastic polyps.
A form of heart failure characterized by elevated cardiac output. This may be seen in patients with heart failure and hyperthyroidism, anemia, pregnancy, arteriovenous fistulae, and others.
An abnormal elevation of the C-reactive protein level in serum.
An inflammatory reaction of the skin to various organic and inorganic antigens. It is characterized by tumor-like masses or nodules of granulomatous tissue comprised of activated histiocytes, epitheliod cells, and multinucleated giant cells.
A circumscribed neoplasm that arises from the glandular epithelium of the duodenum. Morphologically, it is characterized by a proliferation of neoplastic glandular cells and it is associated with dysplasia. According to the growth pattern, it may be classified as tubular, villous, or tubulovillous.
A type of dystonia that is localized to a specific part of the body.
Increased susceptibility to ear infections, as manifested by recurrent episodes of ear infections.
A finding indicating a decrease in the volume of blood ejected during ventricular heart contraction.
A carcinoma that arises from the esophagus and is not amenable to surgical resection.
A short femur length is defined as either a measurement below the 2.5th percentile for gestational age or a measurement that is less than 0.9 of that predicted by the measured biparietal diameter. The femur should be measured with the bone perpendicular to the ultrasound beam and with epiphyseal cartilages visible but not included in the measurement (pmid:16100637).
A fetal position during delivery in which the spine of the fetus is not aligned with the mother's resulting in the descent into the birth canal in an oblique position.
A fetal position during delivery in which the alignment of the spine of the fetus is not parallel to the mother's spine.
An asymptomatic benign or malignant lesion discovered during an endoscopic, surgical, or radiologic procedure performed for unrelated reasons.
An acute or chronic infectious process affecting the gallbladder.
An anomalous configuration of blood vessels that shunts arterial blood directly into veins without passing through the capillaries and that is located in the stomach.
A malignant neoplasm of the stomach that grows submocosally in the gastric wall. Necrosis and hemorrhage may be visible radiologically. Histologically, spindle cells with abnormal mitotic activity may be visible.
An abnormal connection between arteries and veins, occurring within the vasculature of the gastrointestinal tract.
A polypoid tumor that arises from any part of the gastrointestinal tract and protrudes into the lumen. Representative examples include adenomatous polyps, hyperplastic polyps, and hamartomatous polyps.
An abnormality of the genital system. [HPO:probinson]
An acute or chronic infectious process affecting the gums.
Inflammation of the glomeruli characterized by the accumulation of antibody-antigen immune complexes, resulting in glomerular damage and impaired kidney function.
A non-metastasizing neoplasm that arises from the female reproductive system. Representative examples include uterine corpus leiomyoma, endocervical polyp, and benign ovarian germ cell tumor.
The minimum time between successive cycles of contraction and subsequent relaxation of the heart, usually expressed as beats per minute, obtained from a set of measurements of the heart rate.
A reduction below the normal ratio of the volume of red blood cells to the total volume of blood. []
A contraction of the diaphragm that repeats several times per minute. In humans, the abrupt rush of air into the lungs causes the epiglottis to close, creating a hic sound. Also known as synchronous diaphragmatic flutter (SDF), or singultus, from the Latin singult, the act of catching one's breath while sobbing. The hiccup is an involuntary action involving a reflex arc. [HPO:sdoelken]
A rare movement disorder characterised by involuntary spasmodic contractions of the inspiratory muscles synchronised with larynx closure lasting for more than 48 hours.In rare pathological cases, hiccups may last for more than two days. Recurrent episodes over long periods are also called chronic hiccup. Clinical repercussions of these episodes may include dehydration, weight loss and malnutrition due to difficulty eating, sleep disorders, depression and exhaustion.
Admission and confinement to a HOSPITAL without consent of person or persons confined.
Increased amount of pigmentation in the macula lutea.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the ileum. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A cessation of respiratory airflow that may affect infants of 1 to 23 months old, caused by neurological impairment of the respiratory rhythm or obstruction of airflow through the air passages. The symptoms include cyanosis, pallor or bradycardia and snoring in case of obstructive apnea.
A quality of directional uniformity in material such that physical properties do not vary in different directions. (from Oilfield glossary).
An electrocardiographic finding of a junctional rhythm with a heat rate which is abnormally low. (CDISC)
The presence of multiple lipomas (a type of benign tissue made of fatty tissue).
A disorder characterized by irreversible damage to the liver tissue, leading to complete liver failure. Causes include cirrhosis, viral hepatitis, metastases to the liver, genetic disorders, toxins, and drugs.
A persistent non-neoplastic disorder of the lungs. Representative examples include: chronic obstructive pulmonary disease, chronic bronchitis, emphysema, pulmonary fibrosis, pneumoconiosis, asbestosis, atelectasis, radiation induced pneumonitis, and radiation fibrosis.
The presence of metastatic cancer cells in a lymph node.
The reemergence of Hodgkin lymphoma after a period of remission.
An increased susceptibility to meningitis as manifested by a medical history of recurrent episodes of meningitis.
A reduction in the strength of muscles in multiple anatomic sites.
A primary or metastatic malignant neoplasm that affects the anatomic structures of the neck region.
Ability of the peripheral and central nervous systems to receive, process, and respond to internal and external stimuli
Fever accompanied by a significant reduction in the number of NEUTROPHILS.
A benign or malignant solid pathologic process involving a lymph node.
Failure to follow prescribed regulated course of medicinal substances
A low level of the degree to which oxygen is bound to hemoglobin given as a percentage calculated by dividing the maximum oxygen capacity into the actual oxygen content and multiplying by 100. Oxygen saturation usually is measured using pulse oximetry.
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Increased susceptibility to middle ear infections, as manifested by recurrent episodes of middle ear infections
The inability of the ovaries to function.
A squamous cell carcinoma that arises from the soft palate. It usually presents as an ulcerated or fungating mass.
A circumscribed, solid elevation of skin with no visible fluid that is reddish (erythematous) in color.
A successful invasion of a host by an organism that uses the host for food and shelter.
A primary or metastatic malignant neoplasm involving the parotid gland. Representative examples include carcinoma, malignant mixed tumor, and non-Hodgkin lymphoma.
An infectious process affecting the tissues that surround and support the teeth.
An accumulation of fluid in one or more of the perinephric spaces, which consist of the subcapsular, perirenal, anterior and posterior pararenal spaces. This abnormality can be demonstrated by cross-sectional imaging, particularly computed tomography.
Disease involving the common PERONEAL NERVE or its branches, the deep and superficial peroneal nerves. Lesions of the deep peroneal nerve are associated with PARALYSIS of dorsiflexion of the ankle and toes and loss of sensation from the web space between the first and second toe. Lesions of the superficial peroneal nerve result in weakness or paralysis of the peroneal muscles (which evert the foot) and loss of sensation over the dorsal and lateral surface of the leg. Traumatic injury to the common peroneal nerve near the head of the FIBULA is a relatively common cause of this condition. (From Joynt, Clinical Neurology, 1995, Ch51, p31)
Carcinoma, predominantly squamous cell, arising from the epithelial cells of the pharynx.
An increased susceptibility to pharyngitis as manifested by a history of recurrent pharyngitis.
Increased susceptibility to aspiration pneumonia, defined as pneumonia due to breathing in foreign material, as manifested by a medical history of repeated episodes of aspiration pneumonia.
A benign polypoid neoplasm of an epithelial lining projecting into a lumen or cavity. (CDISC)
Any adverse event that arises in the six week period immediately following the delivery of a fetus.
An electrocardiographic tracing demonstrating frequent premature ventricular contractions that exceed an acceptable, predetermined threshold. Different thresholds may apply to different patient populations.
An electrocardiographic finding of premature ventricular complexes which have two or more distinct morphologies, suggesting origin at more than one ventricular site. (CDISC)
An acute or chronic bacterial infection that affects the prostate gland.
A psychotic disorder characterized by prominent hallucinations or delusions that have been determined to be etiologically linked to a general medical condition.
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
A number of small lung lesions characterized by small round masses of 2- to 3-mm in diameter. They are usually detected by chest CT scans (COMPUTED TOMOGRAPHY, X-RAY). Such nodules can be associated with metastases of malignancies inside or outside the lung, benign granulomas, or other lesions.
The branch of pathology that focuses the causes and nature and effects of diseases of the lungs and respiratory structures.
A squamous cell carcinoma that arises from the pyriform sinus. Patients usually present with advanced stage disease and the prognosis is poor.
Disease involving the RADIAL NERVE. Clinical features include weakness of elbow extension, elbow flexion, supination of the forearm, wrist and finger extension, and thumb abduction. Sensation may be impaired over regions of the dorsal forearm. Common sites of compression or traumatic injury include the AXILLA and radial groove of the HUMERUS.
A heterogeneous and/or septated cyst located in the kidney.
Functional anomaly of the kidney persisting for at least three months.
An autoimmune disorder characterised by the association of primary biliary cirrhosis with limited cutaneous systemic sclerosis. Onset occurs between 30-65 years. Occurs sporadically, but rare familial cases with an unknown inheritance pattern have been observed. There is no cure and management is mainly supportive.
A blood clot in the right atrium of the heart.
Inflammation of the sacroiliac joint, generally accompanied by lower back pain.
The least progressive form of SYSTEMIC SCLERODERMA with skin thickening restricted to the face, neck and areas distal to the elbows and/or knees, sparing the trunk. The CREST SYNDROME is a form of limited scleroderma.
A benign or malignant neoplasm that occurs in sella turcica. Representative examples include craniopharyngioma and pituitary gland adenoma.
Accumulation of blood in the SUBDURAL SPACE with delayed onset of neurological symptoms. Symptoms may include loss of consciousness, severe HEADACHE, and deteriorating mental status.
Accumulation of blood in the SUBDURAL SPACE with acute onset of neurological symptoms. Symptoms may include loss of consciousness, severe HEADACHE, and deteriorating mental status.
A squamous cell carcinoma of the larynx that arises from the supraglottic area. Signs and symptoms include dysphagia, a sensation of foreign body in the throat, and hemoptysis. It spreads to the space anterior to the epiglottis, pyriform sinus, and base of the tongue.
Inflammation of the EPIGLOTTIS and supraglottic structures including the PHARYNX; UVULA; base of tongue; and aryepiglottic folds. It is usually caused by HAEMOPHILUS INFLUENZAE in children but often by different organisms in adults.
Syncope following a quick change in position from lying down to standing.
Repeated episodes of obstruction of blood flow due to an embolus, i.e., blood clot that has traveled from its point of origin within the blood stream.
Absence of the thyroid gland in a newborn.
Hurthle cell carcinoma of the thyroid accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms (Sanders and Silverman, 1998). Hurthle cell tumors, also known as oxyphil cell tumors, are composed of cells with increased numbers of mitochondria, which corresponds morphologically to their voluminous, granular, eosinophilic cytoplasm (Maximo et al., 2005).
Inflammation of the palatine tonsils and the posterior pharynx (throat).
Congenital structural abnormalities of the UPPER EXTREMITY.
The need to increase intra-abdominal pressure in order to initiate and maintain voiding.
An abscess that is located in the vagina.
A superficial polypoid lesion that arises from the vagina. It is characterized by the presence of a fibroblastic stroma which is often myxoid, covered by squamous epithelial cells.
An electrocardiographic finding of ventricular tachycardia less than 30 seconds in duration.
An electrocardiographic finding of ventricular tachycardia greater than 30 seconds in duration.
Warfarin is an oral anti-coagulant used world-wide to treat and prevent thrombotic disorders. While it is highly effective, it has a very narrow therapeutic index making it difficult to dose correctly. Genetic variants in both cytochrome P450-2C9 (CYP2C9) and vitamin K-epoxide reductase complex (VKORC1) enzymes, along with non-genetic factors, are known to affect warfarin dose variability. Patients with specific variants in the gene CYP2C9 (the primary warfarin-metabolizing enzyme), such as CYP2C9*2 and CYP2C9*3, may require a lower dose of warfarin as compared to patients without these variants. Patients with a specific variant in VKORC1 (the target enzyme of warfarin), known as -1639G>A or rs9923231, may require a lower warfarin dose as compared to patients who do not have this variant. The combination of CYP2C9 and VKORC1 genetic variants, along with clinical factors, can put some patients at risk for adverse events such as bleeding. Guidelines regarding the use of pharmacogenomic tests in dosing for warfarin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
A laboratory test result indicating a decreased number of white blood cells in the peripheral blood.
A laboratory test result indicating an increased number of white blood cells in the peripheral blood.
Having little chance of being the case or of coming about.
The superficial physical looks, characteristics or qualities of an individual as distinguished from the underlying unseen nature or attributes.
An extranodal non-Hodgkin lymphoma that arises from the colon. The majority are B-cell non-Hodgkin lymphomas.
The 17-valerate derivative of BETAMETHASONE. It has substantial topical anti-inflammatory activity and relatively low systemic anti-inflammatory activity.
Abnormally increased serum levels of alkaline phosphatase activity.
A primary or metastatic malignant neoplasm affecting the adrenal gland.
All FOXP2-related speech and language disorders, regardless of the underlying genetic alteration, have a core phenotype: childhood apraxia of speech (CAS), a disorder of speech motor programming or planning that affects the production, sequencing, timing, and stress of sounds, syllables, and words. All individuals with CAS – whether caused by an alteration of FOXP2 or of an unknown cause – have difficulties in automatically and accurately sequencing speech sounds into syllables, syllables into words, and words into sentences with the correct prosody. Additional findings in FOXP2-related speech and language disorders can include oral motor dyspraxia (difficulty planning or programming oral movements on command); dysarthria (a neuromuscular-based speech disorder that may affect nasal resonance, voice quality, prosody, and breath support for speech); moderate to severe receptive and expressive language disorder; and reading and spelling impairments. The underlying genetic cause of FOXP2-related speech and language disorders is either disruption of FOXP2 only (referred to in this GeneReview as FOXP2-only-related speech and language disorder) or large copy number variants (i.e., contiguous gene deletions), structural variants (i.e., chromosome translocation or inversion), or maternal uniparental disomy of chromosome 7 (UPD7) involving FOXP2 (here referred to as FOXP2-plus speech and language disorders). The genetic alteration determines if only speech and language problems are present (FOXP2-only-related speech and language disorder) or if more global developmental and behavioral issues are likely to be present as well (FOXP2-plus speech and language disorder). In FOXP2-only-related disorders, nonverbal (performance) IQ is typically more preserved compared to verbal IQ. Fine motor skills may be impaired (e.g., buttoning clothes, tying shoelaces), yet gross motor skills are normal. Autistic features and dysmorphic findings have been reported in a few affected individuals. In FOXP2-plus-related disorders oral motor deficits, global developmental delay, and autism spectrum disorder are common.
Chiari malformation type I (CM1) is the protrusion of the cerebellar tonsils through the foramen magnum, defined radiologically as tonsillar descent of 5 mm or more. CM1 is associated with syringomyelia (see 186700) in up to 80% of cases. Although many individuals with CM1 are asymptomatic, the malformation can cause headaches, ocular disturbances, otoneurologic disturbances, lower cranial nerve signs, cerebellar ataxia, or spasticity. Onset of symptoms is usually in the third decade of life (Speer et al., 2003). Since many cases of CM1 are asymptomatic, prevalence estimates may not be accurate. However, a retrospective investigation of brain MRIs reported the prevalence of CM1 to be 1 in 1,280 individuals (Meadows et al., 2000).
An astrocytoma that arises from the cerebral hemispheres.
A kind of ataxia that affects movements of the extremities.
Rubral tremor is characterized by a slow coarse tremor at rest that is exacerbated by postural adjustments and by guided voluntary movements.
The reemergence of a brain neoplasm after a period of remission.
A malignant neoplasm that arises from the brain. Representative examples include anaplastic astrocytoma, glioblastoma, and lymphoma.
Non-malignant neoplasms that arise from cerebellar tissue. During childhood the most common form is pilocytic astrocytoma although fibrillary astrocytomas may also occur. These tumors may present with slowly progressive signs caused by a slowly expanding mass lesion or acutely due to hemorrhage of a vascular tumor. Clinical signs and symptoms may include ataxia, nystagmus, spasticity long tract signs, headache, nausea, vomiting, papilledema, diplopia, spasticity, and weakness, etc.)
Outpouching of BASILAR ARTERY at the base of the skull. The basilar artery is the most important artery in the posterior cerebral circulation.
A widening (ballooning) localized in the wall of the posterior communicating artery. []
A brain aneurysm is an abnormal bulge or ballooning in the wall of an artery in the brain. They are sometimes called berry aneurysms because they are often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, begin to leak blood, or burst. If a brain aneurysm presses on nerves in your brain, it can cause signs and symptoms. These can include. -A droopy eyelid . -Double vision or other changes in vision . -Pain above or behind the eye . -A dilated pupil . -Numbness or weakness on one side of the face or body . Treatment depends on the size and location of the aneurysm, whether it is infected, and whether it has burst. If a brain aneurysm bursts, symptoms can include a sudden, severe headache, nausea and vomiting, stiff neck, loss of consciousness, and signs of a stroke. Any of these symptoms requires immediate medical attention. NIH: National Heart, Lung, and Blood Institute.
A form of cerebral palsy where no predominant motion can be determined; when it is a mixed CP form, i.e. spasticity with ataxia and/or dyskinesia, the child should be classified according to the dominant clinical feature
Cockayne syndrome is a rare disorder characterized by an abnormally small head size (microcephaly), a failure to gain weight and grow at the expected rate (failure to thrive) leading to very short stature, and delayed development. The signs and symptoms of this condition are usually apparent from infancy, and they worsen over time. Most affected individuals have an increased sensitivity to sunlight (photosensitivity), and in some cases even a small amount of sun exposure can cause a sunburn or blistering of the skin. Other signs and symptoms often include hearing loss, vision loss, severe tooth decay, bone abnormalities, hands and feet that are cold all the time, and changes in the brain that can be seen on brain scans.People with Cockayne syndrome have a serious reaction to an antibiotic medication called metronidazole. If affected individuals take this medication, it can cause life-threatening liver failure.Cockayne syndrome is sometimes divided into types I, II, and III based on the severity and age of onset of symptoms. However, the differences between the types are not always clear-cut, and some researchers believe the signs and symptoms reflect a spectrum instead of distinct types. Cockayne syndrome type II is also known as cerebro-oculo-facio-skeletal (COFS) syndrome, and while some researchers consider it to be a separate but similar condition, others classify it as part of the Cockayne syndrome disease spectrum.
Genetic based difficulty in distinguishing colors.
A level of awareness and arousal other than normal.
Febrile seizures with focal semiology, duration of more than 15 minutes, or occurring in a cluster of 2 or more convulsions within 24 hours.
Heterogeneous group of neurodegenerative disorders characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Multiple subtypes or forms are recognized based on presence or absence of TAU PROTEIN inclusions. FTLD includes three clinical syndromes: FRONTOTEMPORAL DEMENTIA, semantic dementia, and PRIMARY PROGRESSIVE NONFLUENT APHASIA.
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the limbs.
Viral encephalitis that is transmitted by mosquitos.
A genetic epilepsy of childhood with characteristics of drug-resistant seizures often induced by fever, presenting in previously healthy children, and which frequently leads to cognitive and motor impairment. Seizures can regress in adulthood but most patients have ongoing seizures that are refractory to medication. Around 85% of cases are due to a mutation or deletion in the SCN1A gene (2q24.3), encoding a voltage-gated sodium channel essential for the excitability of neurons. In families with a known SCN1A mutation, inheritance is autosomal dominant.
FRAXE mental retardation is a form of mild to moderate mental retardation associated with learning difficulties, communication deficits, attention problems, hyperactivity, and autistic behavior (summary by Bensaid et al., 2009). FRAXE is associated with a fragile site on chromosome Xq28 and is the cause of nonsyndromic X-linked mental retardation in 1 of 50,000 newborn males. The disorder can be caused either by silencing of the FMR2 gene as a consequence of a CCG expansion located upstream of this gene or by deletion within the gene (Stettner et al., 2011).
Epimerase deficiency galactosemia (GALE deficiency galactosemia) is a continuum comprising three forms: Generalized. Enzyme activity is profoundly decreased in all tissues tested. Peripheral. Enzyme activity is deficient in red blood cells (RBC) and circulating white blood cells, but normal or near normal in all other tissues. Intermediate. Enzyme activity is deficient in red blood cells and circulating white blood cells and less than 50% of normal levels in other cells tested. Infants with generalized epimerase deficiency galactosemia develop clinical findings on a regular milk diet (which contains lactose, a disaccharide of galactose and glucose); manifestations include hypotonia, poor feeding, vomiting, weight loss, jaundice, hepatomegaly, liver dysfunction, aminoaciduria, and cataracts. Prompt removal of galactose/lactose from their diet resolves or prevents these acute symptoms. In contrast, neonates with the peripheral or intermediate form generally remain clinically well even on a regular milk diet and are usually only identified by biochemical testing, often in newborn screening programs.
Pompe disease is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function normally.Researchers have described three types of Pompe disease, which differ in severity and the age at which they appear. These types are known as classic infantile-onset, non-classic infantile-onset, and late-onset.The classic form of infantile-onset Pompe disease begins within a few months of birth. Infants with this disorder typically experience muscle weakness (myopathy), poor muscle tone (hypotonia), an enlarged liver (hepatomegaly), and heart defects. Affected infants may also fail to gain weight and grow at the expected rate (failure to thrive) and have breathing problems. If untreated, this form of Pompe disease leads to death from heart failure in the first year of life.The non-classic form of infantile-onset Pompe disease usually appears by age 1. It is characterized by delayed motor skills (such as rolling over and sitting) and progressive muscle weakness. The heart may be abnormally large (cardiomegaly), but affected individuals usually do not experience heart failure. The muscle weakness in this disorder leads to serious breathing problems, and most children with non-classic infantile-onset Pompe disease live only into early childhood.The late-onset type of Pompe disease may not become apparent until later in childhood, adolescence, or adulthood. Late-onset Pompe disease is usually milder than the infantile-onset forms of this disorder and is less likely to involve the heart. Most individuals with late-onset Pompe disease experience progressive muscle weakness, especially in the legs and the trunk, including the muscles that control breathing. As the disorder progresses, breathing problems can lead to respiratory failure.
Headache triggered by coughing or straining in the absence of an intracranial disorder.
A secondary headache disorder attributed to low CEREBROSPINAL FLUID pressure caused by SPINAL PUNCTURE, usually after dural or lumbar puncture.
Homocystinuria caused by cystathionine ß-synthase (CBS) deficiency is characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (excessive height, long limbs, scolioisis, and pectus excavatum), vascular system (thromboembolism), and CNS (developmental delay/intellectual disability). All four ? or only one ? of the systems can be involved; expressivity is variable for all of the clinical signs. It is not unusual for a previously asymptomatic individual to present in adult years with only a thromboembolic event that is often cerebrovascular. Two phenotypic variants are recognized, B6-responsive homocystinuria and B6-non-responsive homocystinuria. B6-responsive homocystinuria is usually milder than the non-responsive variant. Thromboembolism is the major cause of early death and morbidity. IQ in individuals with untreated homocystinuria ranges widely, from 10 to 138. In B6-responsive individuals the mean IQ is 79 versus 57 for those who are B6-non-responsive. Other features that may occur include: seizures, psychiatric problems, extrapyramidal signs (e.g., dystonia), hypopigmentation of the skin and hair, malar flush, livedo reticularis, and pancreatitis.
Huntington disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition).Adult-onset Huntington disease, the most common form of this disorder, usually appears in a person's thirties or forties. Early signs and symptoms can include irritability, depression, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many people with Huntington disease develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these movements become more pronounced. Affected individuals may have trouble walking, speaking, and swallowing. People with this disorder also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with the adult-onset form of Huntington disease usually live about 15 to 20 years after signs and symptoms begin.A less common form of Huntington disease known as the juvenile form begins in childhood or adolescence. It also involves movement problems and mental and emotional changes. Additional signs of the juvenile form include slow movements, clumsiness, frequent falling, rigidity, slurred speech, and drooling. School performance declines as thinking and reasoning abilities become impaired. Seizures occur in 30 percent to 50 percent of children with this condition. Juvenile Huntington disease tends to progress more quickly than the adult-onset form; affected individuals usually live 10 to 15 years after signs and symptoms appear.
Insomnia that has persisted at least one month.
A disorder characterized by impairment of the auditory processing, resulting in deficiencies in the recognition and interpretation of sounds by the brain. Causes include brain maturation delays and brain traumas or tumors.
According to U.S. federal legislation, disabilities involved in understanding or using language, manifested in impaired listening, thinking, talking, reading, writing, or arithmetic skills. Includes perceptual handicaps, brain injury, minimal brain dysfunction, and developmental aphasia. Compare LEARNING DISORDERS.
Necrosis and softening of the white matter around the ventricles in the brain associated with cystic changes.
A medulloblastoma characterized by the presence of nodular, collagenous areas which do not contain reticulin, surrounded by hypercellular areas which contain an intercellular reticulin fiber network.
A malignant neoplasm that has spread from its original site to the two innermost layers of tissue that cover the brain and spinal cord.
A meningioma that affects the cerebral sulcus.
A meningioma that affects the falx cerebri.
RIMA shows preference for the A isoenzyme
A group of genetic degenerative muscle disorders affecting the muscles of the lower arms, hands, lower legs, and feet.
Focal seizure with eyelid myoclonia, not eyelid myoclonias in the context of absence seizures.
Myoclonus that occurs during the initial phases of sleep.
An umbrella term for diseases which have chronic muscle inflammation and weakness of unknown etiology. The types of idiopathic inflammatory myopathy are further defined by either clinicopathologic criteria or by the presence of certain autoantibodies.
Focal myositis is a rare inflammatory myopathy characterized by a localized swelling of skeletal muscle that is usually located in the lower extremities.
A localized myotonic contraction in a muscle in reaction to percussion (tapping with the examiner's finger, a rubber percussion hammer, or a similar object).
Narcolepsy is a chronic sleep disorder that disrupts the normal sleep-wake cycle. Although this condition can appear at any age, it most often begins in adolescence.Narcolepsy is characterized by excessive daytime sleepiness. Affected individuals feel tired during the day, and several times a day they may experience an overwhelming urge to sleep. ""Sleep attacks"" can occur at unusual times, such as during a meal or in the middle of a conversation. They last from a few seconds to a few minutes and often lead to a longer nap, after which affected individuals wake up feeling refreshed.Another common feature of narcolepsy is cataplexy, which is a sudden loss of muscle tone in response to strong emotion (such as laughing, surprise, or anger). These episodes of muscle weakness can cause an affected person to slump over or fall, which occasionally leads to injury. Episodes of cataplexy usually last just a few seconds, and they may occur from several times a day to a few times a year. Most people diagnosed with narcolepsy also have cataplexy. However, some do not, which has led researchers to distinguish two major forms of the condition: narcolepsy with cataplexy and narcolepsy without cataplexy.Narcolepsy also affects nighttime sleep. Most affected individuals have trouble sleeping for more than a few hours at night. They often experience vivid hallucinations while falling asleep (hypnogogic hallucinations) or while waking up (hypnopompic hallucinations). Affected individuals often have realistic and distressing dreams, and they may act out their dreams by moving excessively or talking in their sleep. Many people with narcolepsy also experience sleep paralysis, which is an inability to move or speak for a short period while falling asleep or awakening. The combination of hallucinations, vivid dreams, and sleep paralysis is often frightening and unpleasant for affected individuals.Some people with narcolepsy have all of the major features of the disorder, while others have only one or two. Most of the signs and symptoms persist throughout life, although episodes of cataplexy may become less frequent with age and treatment.
neoplasms or cancers that are caused or exacerbated by the exposure to radiation or radionuclides.
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a 'fingerprint' profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with CLN3 (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
Tumor (An abnormal mass of tissue resulting from abnormally dividing cells) of the nasal cavity.
A well-differentiated (WHO grade II), diffusely infiltrating neuroglial tumor, typically located in the cerebral hemispheres. It is composed predominantly of cells which morphologically resemble oligodendroglia. The neoplastic cells have rounded homogeneous nuclei and, on paraffin sections, a swollen, clear cytoplasm ('honeycomb' appearance). (Adapted from WHO)
Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement.
Hereditary inflammation conditions, characterized by recurrent episodes of systemic inflammation. Common symptoms include recurrent fever, rash, arthritis, fatigue, and secondary AMYLOIDOSIS. Hereditary autoinflammatory diseases are associated with mutations in genes involved in regulation of normal inflammatory process and are not caused by AUTOANTIBODIES, or antigen specific T-LYMPHOCYTES.
Malignant growth of cells in the peripheral nervous system (PNS)or Autonomic Nervous System (ANS), without specification as to location
A reduction in phenylalanine 4-monooxygenase activity.
An increased concentration of L-phenylalanine in the blood.
A fear of sounds, which can include fear of voices, including one's own voice, in addition to other sounds.
A type of primitive reflex characterized by an involuntary contraction of the mentalis muscle of the chin caused by stimulation of the thenar eminence of the palm.
An inherited malignant tumor that originates in the nuclear layer of the retina. A predisposition to retinoblastoma has been associated with 13q14 cytogenetic abnormalities. Patients with the inherited form appear to be at increased risk for secondary nonocular malignancies such as osteosarcoma, malignant fibrous histiocytoma, and fibrosarcoma.
A retinoblastoma that occurs in a patient without a family history of the disease.
A transitory alteration in movement, sensation or autonomic nerve function due to abnormal electric activity in a localized area of the cerebral cortex, usually without change in awareness or alertness. Symptoms vary with different lesion locations and may include but not limited to the motor (e.g. rhythmic muscle contractions in one area of the body), somatosensory and sensory alterations manifested by abnormal numbness, paresthesias or other hallucinations, including several types of aura; autonomic and psychic symptoms, e.g. with changes in speech, thought, personality, mood, sensation of deja vu or hallucinations.
In a review of various classification schemes for sleep disorders, Thorpy (1990) listed 'short sleeper' under the broad category of 'disorders of initiating and maintaining sleep' (DIMS); however, the short sleeper phenotype or trait is not considered a sleep disorder. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group. See also familial advanced sleep-phase syndrome (FASPS; 604348), which is a distinct disorder characterized by very early sleep onset and offset.
A cognitive or behavioral change that lasts for at least 30 minutes, with evidence of seizures on electroencephalogram.
Syncope followed by tonic or tonic-clonic movements due to cortical depression and not as a result of a cortical electrical seizure
An extremely uncommon form of vasculitis. Eleven documented cases have been reported in the literature, affecting older children and young adults. In contrast to the classic form of temporal arteritis, it is not a systemic disease nor does it cause local symptoms at the temporal area.The term juvenile temporal arteritis was coined by Lie and his colleagues, in 1975, when they reported four cases of an otherwise asymptomatic disease presenting with a painless nodule at the temporal region. None of the cases showed evidence of systemic disease or history of trauma to the temporal region. Excisional biopsy of the lesions revealed a non-giant cell granulomatous inflammation of the temporal arteries with eosinophilic infiltration, intimal proliferation and micro aneurysmal disruption of the media. The disease has a benign clinical course, is treated by surgical excision and does not recur.
A primary or metastatic malignant neoplasm involving the thymus. This category includes malignant thymomas, thymic lymphomas, primary thymic carcinomas, and metastatic carcinomas from other anatomic sites.
Pulsatile tinnitus is generally classified a kind of objective tinnitus, meaning that it is not only audible to the patient but also to the examiner on auscultation of the auditory canal and/or of surrounding structures with use of an auscultation tube or stethoscope. Usually, pulsatile tinnitus is heard as a lower pitched thumping or booming, a rougher blowing sound which is coincidental with respiration, or as a clicking, higher pitched rhythmic sensation. Pulsatile tinnitus may be associated with vascular abnormalities such as arterioevenous shunts or glomus tumors or the jugular vein, arterial bruits related to a high-riding carotid artery (close to the auditory areas) or carotid stenosis, or venous abnormalities such as a dehiscent jugular bulb or to hypertension. Finally, in some patients, mechanical abnormalities such a spatulous eustachian tubes, palatomyoclonus (small spasms of muscles in the soft palate area), or idiopathic stapedial muscle spasm may represent the underlying cause of pulsatile tinnitus.
A primary or metastatic malignant neoplasm that affects the tonsil.
A type of resting tremor characterized by simultaneous rubbing movements of thumb and index fingers against each other.
A primary or metastatic malignant tumor involving the urinary system. Common tumor types include carcinomas, lymphomas, and sarcomas.
Elongation, dilatation, and/or tortuosity of the vertebrobasilar segment. The definition of VBD includes: (i) diameter of basilar or vertebral artery over 4.5 mm; or (ii) deviation of any portion more than 10 mm from the shortest expected course; and (iii) length of basilar artery over 29.5 mm or length of intracranial vertebral artery over 23.5 mm. [PMID:24765483]
Decreased strength of the vocal fold on both sides.
A loss of the ability to move the vocal fold on one side.
Decreased strength of the vocal fold on one side.
A familial, cerebral arteriopathy mapped to chromosome 19q12, and characterized by the presence of granular deposits in small CEREBRAL ARTERIES producing ischemic STROKE; PSEUDOBULBAR PALSY; and multiple subcortical infarcts (CEREBRAL INFARCTION). CADASIL is an acronym for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. CADASIL differs from BINSWANGER DISEASE by the presence of MIGRAINE WITH AURA and usually by the lack of history of arterial HYPERTENSION. (From Bradley et al, Neurology in Clinical Practice, 2000, p1146)
A primary, noninvasive, slow growing neoplasm of the brain that occurs above the cerebellar tentorium. Representative examples include craniopharyngioma, meningioma and pituitary adenoma.
Malignant neoplasms which arise or occur within the intracranial cavity below the tentorium cerebelli. This includes neoplasms within the brain and/or surrounding spaces.
A class of naturally-isolated or recombinant therapeutic peptides used as antiviral and anti-tumor agents. Alpha interferons are cytokines produced by nucleated cells (predominantly natural killer (NK) leukocytes) upon exposure to live or inactivated virus, double-stranded RNA or bacterial products. These agents bind to specific cell-surface receptors, resulting in the transcription and translation of genes containing an interferon-specific response element. The proteins so produced mediate many complex effects, including antiviral effects (viral protein synthesis); antiproliferative effects (cellular growth inhibition and alteration of cellular differentiation); anticancer effects (interference with oncogene expression); and immune-modulating effects (natural killer cell activation, alteration of cell surface antigen expression, and augmentation of lymphocyte and macrophage cytotoxicity). (NCI04)
A recombinant protein which is chemically identical to or similar to endogenous interferon beta with antiviral and anti-tumor activities. Endogenous interferons beta are cytokines produced by nucleated cells (predominantly natural killer cells) upon exposure to live or inactivated virus, double-stranded RNA or bacterial products. These agents bind to specific cell-surface receptors, resulting in the transcription and translation of genes with an interferon-specific response element. The proteins so produced mediate many complex effects, including antiviral (the most important being inhibition of viral protein synthesis), antiproliferative and immune modulating effects. The recombinant therapeutic forms of interferon beta are interferon beta 1-a and interferon beta 1-b. (NCI05)
An X-linked leucodystrophy characterised primarily by spastic gait and autonomic dysfunction. When additional central nervous system (CNS) signs, such as intellectual deficit, ataxia, or extrapyramidal signs, are present, the syndrome is referred to as complicated spastic paraplegia. Spastic paraplegia type 2 is due to missense substitutions affecting the PLP1 gene. PLP1 encodes the proteolipid protein (PLP), the most abundant protein of the myelin sheath in the central nervous system, and its alternatively spliced isoform (DM20). Transmission is X-linked recessive.
An acute lymphoblastic leukemia occurring during adulthood.
Arachnoid cysts are extraparenchymal, nonneoplastic accumulations of fluid with density similar to that of cerebrospinal fluid. They account for approximately 1% of intracranial space-occupying lesions, although studies since the advent of CT scanning suggest a higher percentage. A striking male preponderance has been observed (summary by Wilson et al., 1988).
A type of holoprosencephaly in which the left and right frontal and parietal lobes are fused and the interhemispheric fissure is only present posteriorly.
A benign or malignant neoplasm that arises from the brain or the spinal cord.
A primary malignant neoplasm in a patient who has been already diagnosed with a primary malignant neoplasm in another anatomic site.
Canavan disease is a rare inherited disorder that damages the ability of nerve cells (neurons) in the brain to send and receive messages. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies disrupt the growth or maintenance of the myelin sheath, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses.Neonatal/infantile Canavan disease is the most common and most severe form of the condition. Affected infants appear normal for the first few months of life, but by age 3 to 5 months, problems with development become noticeable. These infants usually do not develop motor skills such as turning over, controlling head movement, and sitting without support. Other common features of this condition include weak muscle tone (hypotonia), an unusually large head size (macrocephaly), and irritability. Feeding and swallowing difficulties, seizures, and sleep disturbances may also develop.The mild/juvenile form of Canavan disease is less common. Affected individuals have mildly delayed development of speech and motor skills starting in childhood. These delays may be so mild and nonspecific that they are never recognized as being caused by Canavan disease.The life expectancy for people with Canavan disease varies. Most people with the neonatal/infantile form live only into childhood, although some survive into adolescence or beyond. People with the mild/juvenile form do not appear to have a shortened lifespan.
Mild Canavan disease (CD) is a neurodegenerative disorder characterized by mild speech delay or motor development.
Machado-Joseph disease type 1 is a rare, usually severe subtype of Machado-Joseph disease (SCA3/MJD, see this term) characterized by the presence of marked pyramidal and extrapyramidal signs.
Machado-Joseph disease type 2 is a subtype of Machado-Joseph disease (SCA3/MJD, see this term) with intermediate severity characterized by an intermediate age of onset, cerebellar ataxia and external progressive ophthalmoplegia, with variable pyramidal and extrapyramidal signs.
Machado-Joseph disease type 3 is a subtype of Machado-Joseph disease (SCA3/MJD, see this term) of milder severity characterized by late onset, slower progression, and peripheral amyotrophy.
Lymphangioleiomyomatosis (LAM) is a condition that affects the lungs, the kidneys, and the lymphatic system. The lymphatic system consists of a network of vessels that transport lymph fluid and immune cells throughout the body. Lymph fluid helps exchange immune cells, proteins, and other substances between the blood and tissues.LAM is found almost exclusively in women. It often occurs as a feature of an inherited syndrome called tuberous sclerosis complex. When LAM occurs alone it is called isolated or sporadic LAM.Signs and symptoms of LAM most often appear during a woman's thirties. Affected women have an overgrowth of abnormal smooth muscle-like cells (LAM cells) in the lungs, resulting in the formation of lung cysts and the destruction of normal lung tissue. They may also have an accumulation of fluid in the cavity around the lungs (chylothorax).The lung abnormalities resulting from LAM may cause difficulty breathing (dyspnea), chest pain, and coughing, which may bring up blood (hemoptysis). Many women with this disorder have recurrent episodes of collapsed lung (spontaneous pneumothorax). The lung problems may be progressive and, without lung transplantation, may eventually lead to limitations in activities of daily living, the need for oxygen therapy, and respiratory failure. Although LAM cells are not considered cancerous, they may spread between tissues (metastasize). As a result, the condition may recur even after lung transplantation.Women with LAM may develop cysts in the lymphatic vessels of the chest and abdomen. These cysts are called lymphangioleiomyomas. Affected women may also develop tumors called angiomyolipomas made up of LAM cells, fat cells, and blood vessels. Angiomyolipomas usually develop in the kidneys. Internal bleeding is a common complication of angiomyolipomas.
A central nervous system embryonal tumor, not otherwise specified arising from the cerebral hemispheres.
A benign neoplasm comprised of neoplastic ganglion and glial cells.
A malignant neurilemmoma with nerve sheath differentiation. It is often associated with NEUROFIBROMATOSIS 1 and RHABDOMYOSARCOMA.
A rare, almost always benign tumor composed entirely of neoplastic perineurial cells. It may occur in the soft tissues, intraneurally or in mucosal sites.
A form of frontotemporal dementia with characteristics of agrammatism, laborious speech, alexia, and agraphia, frequently accompanied by apraxia of speech. Language comprehension is relatively preserved.
A group of enzymatic disorders affecting the nervous system and to a variable degree the skeletal system, lymphoreticular system, and other organs. The conditions are marked by an abnormal accumulation of catabolic material within lysosomes.
A pathological condition caused by impaired blood flow in the basal regions of cerebral hemispheres (BASAL GANGLIA), such as INFARCTION; HEMORRHAGE; or ISCHEMIA in vessels of this brain region including the lateral lenticulostriate arteries. Primary clinical manifestations include involuntary movements (DYSKINESIAS) and muscle weakness (HEMIPARESIS).
Intracranial bleeding into the PUTAMEN, a BASAL GANGLIA nucleus. This is associated with HYPERTENSION and lipohyalinosis of small blood vessels in the putamen. Clinical manifestations vary with the size of hemorrhage, but include HEMIPARESIS; HEADACHE; and alterations of consciousness.
Brain dysfunction or damage caused by acquired (i.e., non-inborn) metabolic disorders. Associated conditions include ENDOCRINE DISEASES; WATER-ELECTROLYTE IMBALANCE; KIDNEY DISEASES; LIVER DISEASES; anoxia (HYPOXIA, BRAIN); nutritional disorders (see NUTRITIONAL AND METABOLIC DISEASES); an encephalopathy associated with HEMODIALYSIS; and other disorders. (From Plum & Posner, Diagnosis of Stupor and Coma, 3rd ed, pp208-260)
Disorders characterized by defective transport of amino acids across cell membranes. These include deficits in transport across brush-border epithelial cell membranes of the small intestine (MICROVILLI) and KIDNEY TUBULES; transport across the basolateral membrane; and transport across the membranes of intracellular organelles. (From Nippon Rinsho 1992 Jul;50(7):1587-92)
Glycine encephalopathy, also known as nonketotic hyperglycinemia (NKH), is an inborn error of glycine metabolism defined by deficient activity of the glycine cleavage enzyme and, as a consequence, accumulation of large quantities of glycine in all body tissues including the brain. The majority of glycine encephalopathy presents in the neonatal period (85% as the neonatal severe form and 15% as the neonatal attenuated form). Of those presenting in infancy, 50% have the infantile attenuated form and 50% have the infantile severe form. Overall, 20% of all children presenting as either neonates or infants have a less severe outcome, defined as developmental quotient greater than 20. A minority of patients have mild or atypical forms of glycine encephalopathy. The neonatal form manifests in the first hours to days of life with progressive lethargy, hypotonia, and myoclonic jerks leading to apnea and often death. Surviving infants have profound intellectual disability and intractable seizures. The infantile form is characterized by hypotonia, developmental delay, and seizures. The atypical forms range from milder disease, with onset from late infancy to adulthood, to rapidly progressing and severe disease with late onset.
Citrullinemia type I is a rare autosomal recessive urea cycle defect characterized biologically by hyperammonemia and clinically by progressive lethargy, poor feeding and vomiting in the neonatal form (Acute neonatal citrullinemia type I, see this term) and by variable hyperammonemia in the later-onset form (Adult-onset citrullinemia type I, see this term).
A rare and severe disorder of urea cycle metabolism most commonly characterised by either a neonatal-onset of severe hyperammonaemia that occurs few days after birth and manifests with lethargy, vomiting, hypothermia, seizures, coma and death or a presentation outside the newborn period at any age with (sometimes) milder symptoms of hyperammonaemia. The disease is due to mutations in the CPS1 gene (2p) that encodes carbamoyl-phosphate synthetase I (CPS1), an enzyme located in the mitochondrial matrix of hepatocytes and epithelial cells of intestinal mucosa that controls the first step of the urea cycle where ammonia is converted into carbamoyl-phosphate. Mutations in this gene lead to an interruption in the urea cycle and excess nitrogen is not converted to urea for excretion by the kidneys, leading to hyperammonemia. Inherited in an autosomal recessive manner.
A rare sleep disorder characterized by prolonged sleep at night and extreme sleepiness during the day. There are no apparent causes. This disorder affects the ability to function.
Non-24-hour sleep-wake disorder (non-24 disorder), also known as hypernychthemeral syndrome, is a circadian rhythm sleep disorder characterized by non-synchronization to a 24-hour day leading to insomnia and daytime sleepiness with sometimes severe associated manifestations.
A sleep disorder characterized by grinding and clenching of the teeth and forceful lateral or protrusive jaw movements. Sleep bruxism may be associated with TOOTH INJURIES; TEMPOROMANDIBULAR JOINT DISORDERS; sleep disturbances; and other conditions.
A disorder characterized by episodes of vigorous and often violent motor activity during REM sleep (SLEEP, REM). The affected individual may inflict self injury or harm others, and is difficult to awaken from this condition. Episodes are usually followed by a vivid recollection of a dream that is consistent with the aggressive behavior. This condition primarily affects adult males. (From Adams et al., Principles of Neurology, 6th ed, p393)
Excessive periodic leg movements during sleep that cause micro-arousals and interfere with the maintenance of sleep. This condition induces a state of relative sleep deprivation which manifests as excessive daytime hypersomnolence. The movements are characterized by repetitive contractions of the tibialis anterior muscle, extension of the toe, and intermittent flexion of the hip, knee and ankle. (Adams et al., Principles of Neurology, 6th ed, p387)
A heterogeneous group of primarily familial EPILEPSY disorders characterized by myoclonic seizures, tonic-clonic seizures, ataxia, progressive intellectual deterioration, and neuronal degeneration. These include LAFORA DISEASE; MERRF SYNDROME; NEURONAL CEROID-LIPOFUSCINOSIS; sialidosis (see MUCOLIPIDOSES), and UNVERRICHT-LUNDBORG SYNDROME.
The action myoclonus-renal failure syndrome is an autosomal recessive progressive myoclonic epilepsy associated with renal failure. Cognitive function is preserved (Badhwar et al., 2004). Some patients do not develop renal failure (Dibbens et al., 2009). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive disorder of ataxia, myoclonus, epilepsy, and progressive intellectual deterioration in children and ataxia, choreoathetosis, and dementia or character changes in adults. Onset ranges from before age one year to age 72 years; mean age of onset is 31.5 years. The clinical presentation varies depending on the age of onset. The cardinal features in adults are ataxia, choreoathetosis, and dementia. Cardinal features in children are progressive intellectual deterioration, behavioral changes, myoclonus, and epilepsy.
Progressive myoclonus epilepsy, Lafora type (also known as Lafora disease [LD]) is characterized by focal occipital seizures presenting as transient blindness or visual hallucinations and fragmentary, symmetric, or generalized myoclonus beginning in previously healthy individuals at age eight to 19 years (peak 14-16 years). Generalized tonic-clonic seizures, atypical absence seizures, atonic seizures, and focal seizures with impaired awareness may occur. The course of the disease is characterized by increasing frequency and intractability of seizures. Status epilepticus with any of the seizure types is common. Cognitive decline becomes apparent at or soon after the onset of seizures. Dysarthria and ataxia appear early while spasticity appears late. Emotional disturbance and confusion are common in the early stages of the disease and are followed by dementia. Most affected individuals die within ten years of onset, usually from status epilepticus or from complications related to nervous system degeneration.
Unverricht-Lundborg disease (EPM1) is a neurodegenerative disorder characterized by onset from age six to 15 years, stimulus-sensitive myoclonus, and tonic-clonic epileptic seizures. Some years after the onset, ataxia, incoordination, intentional tremor, and dysarthria develop. Individuals with EPM1 are mentally alert but show emotional lability, depression, and mild decline in intellectual performance over time.
A rare neurologic disease with characteristics of seizures that are triggered by acoustic stimulation, which can be simple (as in startle epilepsy) or complex (for example musicogenic seizures, seizures triggered by the voice).
Bleeding into structures of BRAIN STEM, including the MIDBRAIN; PONS; or MEDULLA OBLONGATA, as the result of CRANIOCEREBRAL TRAUMA. DIFFUSE AXONAL INJURY is commonly associated. Clinical manifestations may include OCULAR MOTILITY DISORDERS; ATAXIA; PARALYSIS; PERSISTENT VEGETATIVE STATE; and COMA.
A separation (dissection) of the layers of the internal carotid artery wall.
An acquired abnormality resulting from leaked blood from damaged CAROTID ARTERIES, often due to TRAUMA or INFECTION. The leaked blood is contained in the surrounding tissues and forms a pulsatile neck mass.
Gait abnormalities that are a manifestation of nervous system dysfunction. These conditions may be caused by a wide variety of disorders which affect motor control, sensory feedback, and muscle strength including: CENTRAL NERVOUS SYSTEM DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; NEUROMUSCULAR DISEASES; or MUSCULAR DISEASES.
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Loss of the power to comprehend written materials despite preservation of the ability to write (i.e., alexia without agraphia). This condition is generally attributed to lesions that ""disconnect"" the visual cortex of the non-dominant hemisphere from language centers in the dominant hemisphere. This may occur when a dominant visual cortex injury is combined with underlying white matter lesions that involve crossing fibers from the occipital lobe of the opposite hemisphere. (From Adams et al., Principles of Neurology, 6th ed, p483)
NECROSIS occurring in the ANTERIOR CEREBRAL ARTERY system, including branches such as Heubner's artery. These arteries supply blood to the medial and superior parts of the CEREBRAL HEMISPHERE, Infarction in the anterior cerebral artery usually results in sensory and motor impairment in the lower body.
Acute and chronic neurologic disorders associated with the various neurologic effects of ETHANOL. Primary sites of injury include the brain and peripheral nerves.
Inherited disorders characterized by progressive atrophy and dysfunction of anatomically or physiologically related neurologic systems.
A disorder characterized by the degeneration of the nervous system due to autoimmunity. Representative examples include multiple sclerosis, Guillain-Barre syndrome, and myasthenia gravis.
Conditions characterized by loss or dysfunction of myelin (see MYELIN SHEATH) in the brain, spinal cord, or optic nerves secondary to autoimmune mediated processes. This may take the form of a humoral or cellular immune response directed toward myelin or OLIGODENDROGLIA associated autoantigens.
Inherited conditions characterized by a loss of MYELIN in the central nervous system.
Vasculitis affecting the blood vessels of the brain and/or spinal cord.
Bleeding within the SKULL that is caused by systemic HYPERTENSION, usually in association with INTRACRANIAL ARTERIOSCLEROSIS. Hypertensive hemorrhages are most frequent in the BASAL GANGLIA; CEREBELLUM; PONS; and THALAMUS; but may also involve the CEREBRAL CORTEX, subcortical white matter, and other brain structures.
Constriction of arteries in the SKULL due to sudden, sharp, and often persistent smooth muscle contraction in blood vessels. Intracranial vasospasm results in reduced vessel lumen caliber, restricted blood flow to the brain, and BRAIN ISCHEMIA that may lead to hypoxic-ischemic brain injury (HYPOXIA-ISCHEMIA, BRAIN).
Idiopathic inflammation of the VESTIBULAR NERVE, characterized clinically by the acute or subacute onset of VERTIGO; NAUSEA; and imbalance. The COCHLEAR NERVE is typically spared and HEARING LOSS and TINNITUS do not usually occur. Symptoms usually resolve over a period of days to weeks. (Adams et al., Principles of Neurology, 6th ed, p304)
Degenerative or inflammatory conditions affecting the central or peripheral nervous system that develop in association with a systemic neoplasm without direct invasion by tumor. They may be associated with circulating antibodies that react with the affected neural tissue. (Intern Med 1996 Dec;35(12):925-9)
The transitional form of Pelizaeus-Merzbacher disease (PMD) is the intermediate form of PMD (see this term).
Disease involving the median nerve, from its origin at the BRACHIAL PLEXUS to its termination in the hand. Clinical features include weakness of wrist and finger flexion, forearm pronation, thenar abduction, and loss of sensation over the lateral palm, first three fingers, and radial half of the ring finger. Common sites of injury include the elbow, where the nerve passes through the two heads of the pronator teres muscle (pronator syndrome) and in the carpal tunnel (CARPAL TUNNEL SYNDROME).
Disease involving the femoral nerve. The femoral nerve may be injured by ISCHEMIA (e.g., in association with DIABETIC NEUROPATHIES), nerve compression, trauma, COLLAGEN DISEASES, and other disease processes. Clinical features include MUSCLE WEAKNESS or PARALYSIS of hip flexion and knee extension, ATROPHY of the QUADRICEPS MUSCLE, reduced or absent patellar reflex, and impaired sensation over the anterior and medial thigh.
Disease of the TIBIAL NERVE (also referred to as the posterior tibial nerve). The most commonly associated condition is the TARSAL TUNNEL SYNDROME. However, LEG INJURIES; ISCHEMIA; and inflammatory conditions (e.g., COLLAGEN DISEASES) may also affect the nerve. Clinical features include PARALYSIS of plantar flexion, ankle inversion and toe flexion as well as loss of sensation over the sole of the foot. (From Joynt, Clinical Neurology, 1995, Ch51, p32)
A non-neoplastic or neoplastic disorder affecting the olfactory nerve (first cranial nerve).
A non-neoplastic or neoplastic disorder affecting the glossopharyngeal nerve (ninth cranial nerve).
Conditions characterized by impaired transmission of impulses at the NEUROMUSCULAR JUNCTION. This may result from disorders that affect receptor function, pre- or postsynaptic membrane function, or ACETYLCHOLINESTERASE activity. The majority of diseases in this category are associated with autoimmune, toxic, or inherited conditions.
Central core disease (CCD) is characterized by muscle weakness ranging from mild to severe. Most affected individuals have mild disease with symmetric proximal muscle weakness and variable involvement of facial and neck muscles. The extraocular muscles are often spared. Motor development is usually delayed, but in general, most affected individuals acquire independent ambulation. Life span is usually normal. Severe disease is early in onset with profound hypotonia often accompanied by poor fetal movement, spinal deformities, hip dislocation, joint contractures, poor suck, and respiratory insufficiency requiring assisted ventilation. The outcome ranges from death in infancy to survival beyond age five years. The weakness in CCD is not typically progressive.
Tissue NECROSIS in any area of the brain, including the CEREBRAL HEMISPHERES, the CEREBELLUM, and the BRAIN STEM. Brain infarction is the result of a cascade of events initiated by inadequate blood flow through the brain that is followed by HYPOXIA and HYPOGLYCEMIA in brain tissue. Damage may be temporary, permanent, selective or pan-necrosis.
The most common clinical variant of MULTIPLE SCLEROSIS, characterized by recurrent acute exacerbations of neurologic dysfunction followed by partial or complete recovery. Common clinical manifestations include loss of visual (see OPTIC NEURITIS), motor, sensory, or bladder function. Acute episodes of demyelination may occur at any site in the central nervous system, and commonly involve the optic nerves, spinal cord, brain stem, and cerebellum. (Adams et al., Principles of Neurology, 6th ed, pp903-914)
Compounds or factors that act on a specific enzyme to increase its activity.
Agents and factors that activate GTP phosphohydrolase activity.
Brain disorders resulting from inborn metabolic errors, primarily from enzymatic defects which lead to substrate accumulation, product reduction, or increase in toxic metabolites through alternate pathways. The majority of these conditions are familial, however spontaneous mutation may also occur in utero.
Spinocerebellar ataxia type 1 (SCA1) is characterized by progressive cerebellar ataxia, dysarthria, and eventual deterioration of bulbar functions. Early in the disease, affected individuals may have gait disturbance, slurred speech, difficulty with balance, brisk deep tendon reflexes, hypermetric saccades, nystagmus, and mild dysphagia. Later signs include slowing of saccadic velocity, development of up-gaze palsy, dysmetria, dysdiadochokinesia, and hypotonia. In advanced stages, muscle atrophy, decreased deep tendon reflexes, loss of proprioception, cognitive impairment (e.g., frontal executive dysfunction, impaired verbal memory), chorea, dystonia, and bulbar dysfunction are seen. Onset is typically in the third or fourth decade, although childhood onset and late-adult onset have been reported. Those with onset after age 60 years may manifest a pure cerebellar phenotype. Interval from onset to death varies from ten to 30 years; individuals with juvenile onset show more rapid progression and more severe disease. Anticipation is observed. An axonal sensory neuropathy detected by electrophysiologic testing is common; brain imaging typically shows cerebellar and brain stem atrophy.
Spinocerebellar ataxia type 2 (SCA2) is characterized by progressive cerebellar ataxia, including nystagmus, slow saccadic eye movements, and in some individuals, ophthalmoparesis or parkinsonism. Pyramidal findings are present; deep tendon reflexes are brisk early on and absent later in the course. Age of onset is typically in the fourth decade with a ten- to 15-year disease duration.
Spinocerebellar ataxia type 6 (SCA6) is characterized by adult-onset, slowly progressive cerebellar ataxia, dysarthria, and nystagmus. Mean age of onset is 43 to 52 years. Initial symptoms are gait unsteadiness, stumbling, and imbalance (in ~90%) and dysarthria (in ~10%). Eventually all persons have gait ataxia, upper-limb incoordination, intention tremor, and dysarthria. Dysphagia and choking are common. Visual disturbances may result from diplopia, difficulty fixating on moving objects, horizontal gaze-evoked nystagmus, and vertical nystagmus. Hyperreflexia and extensor plantar responses occur in up to 40%-50%. Basal ganglia signs, including dystonia and blepharospasm, occur in up to 25%. Mentation is generally preserved.
Spinocerebellar ataxia type 7 (SCA7) is characterized by progressive cerebellar ataxia, including dysarthria and dysphagia, and cone-rod and retinal dystrophy with progressive central visual loss resulting in blindness in affected adults. Onset in early childhood or infancy has an especially rapid and aggressive course often associated with failure to thrive and regression of motor milestones.
Pathological processes involving any of the BLOOD VESSELS feeding the SPINAL CORD, such as the anterior and paired posterior spinal arteries or their many branches. Disease processes may include ATHEROSCLEROSIS; EMBOLISM; and ARTERIOVENOUS MALFORMATIONS leading to ISCHEMIA or HEMORRHAGE into the spinal cord (hematomyelia).
Reduced blood flow to the spinal cord which is supplied by the anterior spinal artery and the paired posterior spinal arteries. This condition may be associated with ARTERIOSCLEROSIS, trauma, emboli, diseases of the aorta, and other disorders. Prolonged ischemia may lead to INFARCTION of spinal cord tissue.
NECROSIS induced by ISCHEMIA in the POSTERIOR CEREBRAL ARTERY distribution system which supplies portions of the BRAIN STEM; the THALAMUS; TEMPORAL LOBE, and OCCIPITAL LOBE. Depending on the size and location of infarction, clinical features include OLFACTION DISORDERS and visual problems (AGNOSIA; ALEXIA; HEMIANOPSIA).
An abnormal structural condition of the human body, usually macroscopic, that is common to a variety of different diseases.
Pathological conditions involving ARTERIES in the skull, such as arteries supplying the CEREBRUM, the CEREBELLUM, the BRAIN STEM, and associated structures. They include atherosclerotic, congenital, traumatic, infectious, inflammatory, and other pathological processes.
Blocking of a blood vessel in the SKULL by an EMBOLUS which can be a blood clot (THROMBUS) or other undissolved material in the blood stream. Most emboli are of cardiac origin and are associated with HEART DISEASES. Other non-cardiac sources of emboli are usually associated with VASCULAR DISEASES.
Formation or presence of a blood clot (THROMBUS) in a blood vessel within the SKULL. Intracranial thrombosis can lead to thrombotic occlusions and BRAIN INFARCTION. The majority of the thrombotic occlusions are associated with ATHEROSCLEROSIS.
A headache disorder that occurs exclusively at night, waking the affected individual from sleep.
A congenital abnormality of the arteries and veins that is located in the brain or spina cord, and which may increase the risk of bleeding, possibly resulting in impaired mental or physical function.
Formed by an abnormal connection between arteries within the dura mater and veins that normally drain the brain.
A cavernous hemangioma arising from the central nervous system.
A vascular anomaly characterized by a radial or wedge-shaped arrangement of dilated VEINS draining into a larger vein in the brain, spinal cord, or the meninges. Veins in a venous angioma are surrounded by normal nervous tissue, unlike a CENTRAL NERVOUS SYSTEM CAVERNOUS HEMANGIOMA that lacks intervening nervous tissue. Drainage of venous angioma is fully integrated with the body's venous system, therefore, in most cases there is no clinical signs and rare bleeding.
Bardet-Biedl syndrome (BBS) is characterized by rod-cone dystrophy, truncal obesity, postaxial polydactyly, cognitive impairment, male hypogonadotropic hypogonadism, complex female genitourinary malformations, and renal abnormalities. The visual prognosis for children with BBS is poor. Night blindness is usually evident by age seven to eight years; the mean age of legal blindness is 15.5 years. Birth weight is usually normal, but significant weight gain begins within the first year and becomes a lifelong issue for most individuals. A majority of individuals have significant learning difficulties; a minority have severe impairment on IQ testing. Renal disease is a major cause of morbidity and mortality.
A thrombin-like enzyme from the venom of snakes of the viper/rattlesnake group. Species variants of the enzyme include ANCROD (Agkistrodon rhodostoma (Malayan pit viper)); BATROXOBIN from Bothrops atrox; and crotalase from Crotalus adamanteus (Eastern diamondback rattlesnake). EC 3.4.21.74.
The presence of calculi in a salivary duct or gland.
Bacterial infections of the brain, spinal cord, and meninges, including infections involving the perimeningeal spaces.
Infections of the brain, spinal cord, and meninges caused by parasites.
Infections of the brain, spinal cord, or meninges by single celled organisms of the former subkingdom known as protozoa. The central nervous system may be the primary or secondary site of protozoal infection. These diseases may occur as OPPORTUNISTIC INFECTIONS or arise in immunocompetent hosts.
Infections of the BRAIN; SPINAL CORD; or MENINGES caused by HELMINTHS (parasitic worms).
SCHISTOSOMIASIS of the brain, spinal cord, or meninges caused by infections with trematodes of the genus SCHISTOSOMA (primarily SCHISTOSOMA JAPONICUM; SCHISTOSOMA MANSONI; and SCHISTOSOMA HAEMATOBIUM in humans). S. japonicum infections of the nervous system may cause an acute meningoencephalitis or a chronic encephalopathy. S. mansoni and S. haematobium nervous system infections are associated with acute transverse myelitis involving the lower portions of the spinal cord. (From Joynt, Clinical Neurology, 1998, Ch27, pp61-2)
Infectious processes, including abscesses, effusions, and empyemas which occur in the epidural or subdural spaces surrounding the brain and spinal cord.
Episodic bouts of involuntary movements with dystonic, choreic, ballistic movements, or a combination thereof. There is no loss of consciousness during the attacks. [HPO:probinson]
Substances that possess antiestrogenic actions but can also produce estrogenic effects as well. They act as complete or partial agonist or as antagonist. They can be either steroidal or nonsteroidal in structure.
Nervous system infections caused by tick-borne spirochetes of the BORRELIA BURGDORFERI GROUP. The disease may affect elements of the central or peripheral nervous system in isolation or in combination. Common clinical manifestations include a lymphocytic meningitis, cranial neuropathy (most often a facial neuropathy), POLYRADICULOPATHY, and a mild loss of memory and other cognitive functions. Less often more extensive inflammation involving the central nervous system (encephalomyelitis) may occur. In the peripheral nervous system, B. burgdorferi infection is associated with mononeuritis multiplex and polyradiculoneuritis. (From J Neurol Sci 1998 Jan 8;153(2):182-91)
Rathke's pouch cysts are rarely symptomatic in the first two decades of life though they may produce symptoms in the third and fourth decades of life. When the cysts do present in the first decades of life, the symptoms are generally associated with diabetes insipidus or other conditions related to hypopituitarism.
Signs and symptoms associated with diseases of the muscle, neuromuscular junction, or peripheral nerves.
Disorders of sensory information received from superficial and deep regions of the body. The somatosensory system conveys neural impulses which pertain to proprioception, tactile sensation, thermal sensation, pressure sensation, and pain. PERIPHERAL NERVOUS SYSTEM DISEASES; SPINAL CORD DISEASES; and BRAIN DISEASES may be associated with impaired or abnormal somatic sensation.
An over-the-counter herbal remedy, extracted from North American herb purple coneflower belonging to the Family Asteraceae, with potential immunostimulating and anti-inflammatory activities. Echinacea extract might be helpful to boost the body's immune system and to help fight infections, especially those of the upper respiratory tract. This herbal remedy seems to increase the growth and activity of immune cells, including white blood cells, macrophages and natural killer cells, and to stimulate phagocytosis. Furthermore, echinacoside, one of the components in Echinacea extract, has been shown to inhibit hyaluronidase, whose action increases tissue permeability, thereby Echinacea extract may promote tissue growth for wound healing by preventing bacteria spreading into healthy cells.
A group of rare genetic muscle disorders characterized by hypotonia, muscle weakness, and delayed development of motor skills.
Dyssomnias (i.e., insomnias or hypersomnias) associated with dysfunction of internal sleep mechanisms or secondary to a sleep-related medical disorder (e.g., sleep apnea, post-traumatic sleep disorders, etc.). (From Thorpy, Sleep Disorders Medicine, 1994, p187)
Sleep disorders characterized by impaired arousal from the deeper stages of sleep (generally stage III or IV sleep).
A nocturnal episode characterized by disorientation, grogginess, and, at times, substantial agitation upon awakening from slow-wave sleep or following forced awakenings. These characteristics might present as agitation, crying or moaning, disorientation, and particularly slow mentation on arousal from sleep (i.e., sleep inertia). The duration of episodes is typically 5 to 15 min but they might last up to several hours.
Parasomnias characterized by behavioral abnormalities that occur during the transition between wakefulness and sleep (or between sleep and wakefulness).
Abnormal behavioral or physiologic events that are associated with REM sleep, including REM SLEEP BEHAVIOR DISORDER.
Clinical disturbances of the urinary system.
Ischemic brain damage in which the entire brain is deprived of oxygen. It may be fatal or lead to long term disabilities including developmental delays, intellectual disability, and seizures.
A disorder characterized by a reduction of oxygen in the blood combined with reduced blood flow (ISCHEMIA) to the brain from a localized obstruction of a cerebral artery or from systemic hypoperfusion. Prolonged hypoxia-ischemia is associated with ISCHEMIC ATTACK, TRANSIENT; BRAIN INFARCTION; BRAIN EDEMA; COMA; and other conditions.
The hydrochloride salt form of dexmedetomidine, an imidazole derivate and active d-isomer of medetomidine with analgesic, anxiolytic and sedative activities. Dexmedetomidine selectively binds to and activates presynaptic alpha-2 adrenoceptors located in the brain, thereby inhibiting the release of norepinephrine from synaptic vesicles. This leads to an inhibition of postsynaptic activation of adrenoceptors, which inhibits sympathetic activity, thereby leading to analgesia, sedation and anxiolysis.
An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell. [GOC:bf, GOC:mtg_signaling_feb11, PMID:20811974, PMID:9561267]
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A disorder characterized by recurrent focal onset seizures which have sensory (i.e., olfactory, visual, tactile, gustatory, or auditory) manifestations. Partial seizures that feature alterations of consciousness are referred to as complex partial seizures (EPILEPSY, COMPLEX PARTIAL).
Seizures with sustained increase in muscle contraction in parts of the body lasting a few seconds to minutes.
Inflammation of ARTERIES in the CENTRAL NERVOUS SYSTEM that occurs in patients with ACQUIRED IMMUNODEFICIENCY SYNDROME or AIDS-RELATED OPPORTUNISTIC INFECTIONS.
Inflammation that includes the brain, spinal cord and surrounding tissues secondary to systemic lupus erythematosus (SLE); it is associated with neurological and/or psychiatric features.
Infections of the nervous system caused by fungi of the genus ASPERGILLUS, most commonly ASPERGILLUS FUMIGATUS. Aspergillus infections may occur in immunocompetent hosts, but are more prevalent in individuals with IMMUNOLOGIC DEFICIENCY SYNDROMES. The organism may spread to the nervous system from focal infections in the lung, mastoid region, sinuses, inner ear, bones, eyes, gastrointestinal tract, and heart. Sinus infections may be locally invasive and enter the intracranial compartment, producing MENINGITIS, FUNGAL; cranial neuropathies; and abscesses in the frontal lobes of the brain. (From Joynt, Clinical Neurology, 1998, Ch 27, pp62-3)
Dementia with Lewy bodies (DLB) is a neurodegenerative disorder clinically characterized by dementia and parkinsonism, often with fluctuating cognitive function, visual hallucinations, falls, syncopal episodes, and sensitivity to neuroleptic medication. Pathologically, Lewy bodies are present in a pattern more widespread than usually observed in Parkinson disease (see PD; 168600). Alzheimer disease (AD; 104300)-associated pathology and spongiform changes may also be seen (McKeith et al., 1996; Mizutani, 2000; McKeith et al., 2005).
Early pregnancy loss during the EMBRYO, MAMMALIAN stage of development. In the human, this period comprises the second through eighth week after fertilization.
A group of primary or secondary disorders affecting the muscles. It is characterized by an abnormal reduction in the muscle volume and atrophy. The atrophy may be caused by diseases of the muscle tissues or diseases of the peripheral nerves.
A form of potassium-aggravated myotonia which is cold insensitive, dramatically fluctuating and profoundly worsened by potassium ingestion. Fluctuating myotonia develops during childhood or adolescence and involves the extraocular, bulbar and limb muscles. Myotonia fluctuans is a sodium muscle channelopathy due to missense mutations of the SCN4A gene encoding the alpha subunit of the skeletal muscle voltage-gated sodium channel Nav1.4. Transmission is autosomal dominant.
Clinical characteristics of disease or illness.
An analogue of cyclosporin-A. Valspodar inhibits p-glycoprotein, the multidrug resistance efflux pump, thereby restoring the retention and activity of some drugs in some drug-resistant tumor cells. This agent also induces caspase-mediated apoptosis. (NCI04)
A second generation non-nucleoside reverse transcriptase inhibitor derivative of oxathiin carboxanilide. Uniroyal compound 38 has activity against a wide range of biologically diverse laboratory and clinical strains of HIV-1 but is inactive against HIV-2.
A steroidal compound with antiandrogen activity. Abiraterone inhibits the enzymatic activity of steroid 17alpha-monooxygenase (17alpha-hydrolase/C17,20 lyase complex; CYP17A1), a member of the cytochrome p450 family that catalyzes the 17alpha-hydroxylation of steroid intermediates involved in testosterone synthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels.
A synthetic dolastatin 15 analogue with potential antineoplastic activity. Cemadotin suppresses spindle microtubule dynamics by binding to tubulin, thereby blocking mitosis.
A synthetic derivative of hydroxyethylamine sulfonamide that selectively binds to and inhibits human immunodeficiency virus (HIV) protease.
An orally bioavailable small molecule belonging to the azaspirane class of cationic amphiphilic agents with anti-inflammatory, antineoplastic, and antiangiogenic properties. Atiprimod inhibits the phosphorylation of signal transducer and activator of transcription 3 (STAT3), blocking the signalling pathways of interleukin-6 and vascular endothelial growth factor (VEGF) and downregulating the anti-apoptotic proteins Bcl-2, Bcl-XL, and Mcl-1, thereby inhibiting cell proliferation, inducing cell cycle arrest, and inducing apoptosis.
An orally active alkyl-phosphocholine compound with potential antineoplastic activity. Targeting cellular membranes, perifosine modulates membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis. Perifosine has a lower gastrointestinal toxicity profile than the related agent miltefosine. (NCI04)
A pipecolinate derivative. Functioning as a modulator of P-glycoprotein (P-gp) and multidrug resistance protein (MRP-1), biricodar restores drug sensitivity to cells expressing P-glycoprotein and MRP1, the cellular efflux pumps that are the major causes in tumor cell resistance to chemotherapeutic agents. This agent binds directly to Pgp and MRP-1 and inhibits efflux pump activity, resulting in increased intracellular accumulation and retention of cytotoxic agents.
A 5-ALPHA-REDUCTASE INHIBITOR that is reported to inhibit both type-1 and type2 isoforms of the enzyme and is used to treat BENIGN PROSTATIC HYPERPLASIA.
A synthetic organic compound that selectively inhibits the kinase activity of Mitogen-Activated Protein kinase, preventing cytokine and prostaglandin E2 production. (NCI)
A member of the cryptophycin family of antitumor agents that binds to microtubules, inducing growth arrest and apoptosis in solid tumors. (NCI)
A cationic tri-nuclear platinum complex related to cisplatin. BBR 3464 binds to and forms DNA crosslinks and platinum-DNA adducts, preventing DNA replication and tumor cell division.
An herbal mixture with potential antineoplastic effects. PC-SPES, an herbal supplement containing extracts from 8 herbs including Chrysanthemum morifolium, Ganoderma lucidum (a root fungus), Glycyrrhiza glabra (Spanish liquorice), Isatis indigotica, Panax pseudoginseng, Rabdosia rubescens, Scutellaria baicalensis, and Serona repens (saw palmetto), with potential antineoplastic and antiproliferative effects, specifically in prostate cancer cells. Its exact pharmacology is not fully understood due to the complexity of the herbal mixture and may involve multiple metabolic pathways. Exposure to PC-SPES in vitro has resulted in a decreased expression of genes encoding cell cycle regulatory proteins as well as an upregulation of genes that modulate apoptosis in both androgen-dependent and androgen-independent cells. The PC in the acronym PC-SPES stands for Prostate Cancer, while SPES is the Latin word for hope.
An orally active, synthetic, and potent inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Like other factor Xa inhibitors, fidexaban prevents thrombus formation.
A pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) and a ghrelin mimetic with growth hormone (GH) releasing activity. Ipamorelin mimics ghrelin and binds to the ghrelin receptor (or GH secretagogue receptor, GHSR) in the brain, thereby selectively stimulating the release of GH from the pituitary gland. This results in increased plasma GH levels, which would affect many biological processes. Besides its presence in the brain, GHSR can also be found in the gastrointestinal tract, heart, lung, liver, kidney, pancreas, adipose tissue and immune cells. Unlike other GH releasing peptides, ipamorelin only stimulates GH release in a manner very similar to that of growth hormone releasing hormone.
An orally-available synthetic derivative of the beta-amino acid cispentacin with antifungal properties. Icofungipen blocks isoleucyl-tRNA synthetase and results in inhibition of protein synthesis.
A cell-free mixture comprised of a variety of naturally-derived cytokines obtained from normal, unrelated donor lymphocytes with potential immunostimulatory activity. The cytokines in IRX-2, including interleukin (IL)-1, -2, -6, -8, -10, -12, tumor necrosis factor alpha (TNF-a), interferon-gamma (IFN-g) and colony stimulating factors (CSFs), play vital roles in regulating cellular immunity and may synergistically stimulate a cellular immune response against tumor cells.
A kind of Protein tyrosine kinase inhibitor involved in cell proliferation and differentiation. (NCI)
The hydrochloride salt of a 2-piperazinylbenzimidazole-derivative serotonin type 3 (5-HT3) receptor antagonist with antiemetic activity. Lerisetron specifically binds to 5-HT3 receptors, located peripherally on vagus nerve terminals and centrally in the chemoreceptor trigger zone (CTZ) of the area postrema, which may result in suppression of chemotherapy-induced nausea and vomiting.
A small-molecule inhibitor with activity against viruses in the picornaviridae family, including enterovirus and rhinovirus. Pleconaril binds to a hydrophobic pocket in the major capsid protein and prevents uncoating of the viral RNA genome. In enteroviruses it also prevents the virus from attaching itself to the host cell.
A water soluble analogue of the antineoplastic agent brefeldin A (BFA). (NCI04)
A natural analogue of actinomycin, a chromopeptide antineoplastic antibiotic isolated from the bacterial genus Streptomyces. Actinomycin C2 inhibits DNA replication as well as RNA and protein synthesis by various mechanisms including, intercalating into the minor groove of DNA and interfering with the function of topoisomerase II. In addition, actinomycin C2 appears to block the interaction between the SH2 domain of growth factor receptor-bound protein-2 (GRB2) and the Src homology 2 domain containing transforming protein 1 adaptor protein SHC, which plays a key role in the Ras signaling pathway thereby halting cellular differentiation and proliferation.
A synthetic triterpenoid compound with potential antineoplastic and anti-inflammatory activities. Bardoxolone blocks the synthesis of inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2), two enzymes involved in inflammation and carcinogenesis. This agent also inhibits the interleukin-1 (IL-1)-induced expression of the pro-inflammatory proteins matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-13 (MMP-13) and the expression of Bcl-3; Bcl-3 is an IL-1-responsive gene that preferentially contributes to MMP-1 gene expression.
A synthetic, nonsteroidal derivative of phenyl-furanone with antiinflammatory, antipyretic and analgesic properties and potential antineoplastic properties. Rofecoxib binds to and inhibits the enzyme cyclooxygenase-2 (COX-2), resulting in an inhibition of the conversion of arachidonic acid to prostaglandins. COX-related metabolic pathways may represent key regulators of cell proliferation and neo-angiogenesis. Some epithelial tumor cell types overexpress pro-angiogenic COX-2. (NCI04)
The active ingredient in a substance being studied in the treatment of small cell lung cancer and other types of cancer. It blocks certain enzymes needed for cell division and DNA repair, and it may kill cancer cells. It is a type of camptothecin analog and a type of topoisomerase inhibitor.
An immunotoxin comprised of an anti-B4 (anti-CD19) murine monoclonal antibody linked to the modified plant-derived toxin blocked ricin. The antibody moiety of anti-B4 blocked ricin immunotoxin binds to B lymphocytes that express B4; after internalization of the immunotoxin by the B4-expressing B cell, the ricin moiety cleaves the N-glycosidic bond between the ribose and adenine base at position 4324 in the B lymphocyte 28S ribosomal RNA, resulting in ribosome inactivation, inhibition of protein synthesis, and cell death. Blocked ricin is ricin which has been chemically modified such that the lectin binding sites of the B chain (galactose-binding sites) have been blocked by covalent attachment of affinity ligands, leaving the ribosome-inactivating activity of the ricin A chain intact.
A sterile suspension composed of an extract of bovine pulmonary surfactant with surfactant activity. Calfactant contains phospholipids, neutral lipids, and hydrophobic surfactant-associated proteins B (SP-B) and C (SP-C). Upon intratracheal administration, this agent, mimicking endogenous pulmonary surfactant, lines the alveoli and smallest bronchioles, keeping alveoli open during expiration by lowering surface tension. Resulting improvements in lung compliance and respiratory gas exchange may lead to improvements in ventilation and oxygenation.
A synthetic peptide vaccine consisting of the carboxy terminal peptide (CTP) of human beta chorionic gonadotropin (beta-hCG). Vaccination with CTP-37 may stimulate the host immune system to produce antibodies against beta-HCG, leading to a decrease in the proliferation of tumor cells that overexpress beta-HCG. (NCI04)
A synthetic retinoic acid agent with potential antineoplastic, chemopreventive, teratogenic and embryotoxic properties. Bexarotene selectively binds to and activates retinoid X receptors (RXRs), thereby inducing changes in gene expression that lead to cell differentiation, decreased cell proliferation, apoptosis of some cancer cell types, and tumor regression. (NCI04)
The R-isomer of a synthetic quinoxaline phenoxypropionic acid derivative with proapoptotic and antiproliferative activities. R(+)XK469 selectively inhibits topoisomerase II-beta, blocks activation of MEK/MAPK signaling kinases, stimulates caspases, and upregulates p53-dependent proteins, including cyclins A and B1, thereby arresting cancer cells in the G2/M phase of the cell cycle. Both R(+) and S(-) isomers of this agent are cytotoxic, although the R-isomer is more potent. (NCI05)
A non-iodinated derivative of amiodarone that is used for the treatment of ARRHYTHMIA.
A synthetic pentafluorophenylsulfonamide with potential antineoplastic activity. Batabulin covalently binds to beta tubulin, resulting in a disruption of microtubule polymerization, collapse of the cytoskeleton, cell cycle arrest, and tumor cell apoptosis.
The carbonate salt of lanthanum, a silvery white metallic element of the lanthanoids family, with phosphate binding property. Lanthanum carbonate dissociates in gastric acid to release lanthanum ions, which then binds dietary phosphate. This agent inhibits the absorption of phosphate by forming highly insoluble lanthanum-phosphate complexes that reduce concentrations of serum phosphate and calcium phosphate.
A monoclonal antibody directed against the CD20 protein expressed on the surface of B-lymphocytes and radiolabeled with the radioisotope iodine I 131 with potential antineoplastic activity. Iodine I 131 tositumomab binds to and selectively delivers cyctotoxic radiation to CD20-expressing B-lymphocytes, thereby minimizing systemic radiotoxicity.
A greenish, crystalline inorganic compound that produces toxic gases upon heating. Nickel acetate is used in textile dyeing processes, in electroplating, and as a catalyst intermediate. Exposure to this substance can cause severe dermatitis, skin and asthma-like allergies and causes damage to the lungs, kidneys, gastrointestinal tract and neurological system. Nickel acetate is a known carcinogen and is associated with an increased risk of developing lung and nasal cancers. (NCI05)
A mixture of highly sulfated, monophosphorylated mannose oligosaccharides, derived from the extracellular phosphomannan of the yeast Pichia (Hansenula) holstii, with potential antiangiogenic activity. Phosphomannopentaose sulfate inhibits the endo-beta-D-glucuronidase heparanase, which may interfere with the heparanase-mediated degradation of heparan-sulfate proteoglycans in extracellular matrices, an important step in the metastatic process. This agent may also bind with high affinity to the heparan sulfate-binding domains of vascular endothelial growth factor (VEGF) and fibroblast growth factors 1 and 2, thereby reducing their functional activities and inhibiting VEGF and FGF stimulation of tumor angiogenesis. Increased heparanase activity has been implicated in tumor angiogenesis and metastasis.
An agent that inhibits both mitogen-activated protein kinase kinases 1 and 2 (MEK1 and MEK2), substrates of Raf and phosphorylates extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2), preventing phosphorylation and activation of the Mitogen-Activated Protein Kinase (MAPK) pathways, involved with signal transduction pathways and tumor proliferation.
The hydrochloride salt form of terazosin, a quinazoline derivative with adrenergic antagonistic property. Terazosin hydrochloride selectively inhibits alpha-1 adrenergic receptors, resulting in vasodilation leading to decreased peripheral vascular resistance and a reduced venous return to the heart as well as decreased urethral resistance, which potentially improving urine flow and symptoms related to benign prostatic hyperplasia. In addition, terazosin decreases low-density lipoproteins (LDL) and triglycerides while increasing the concentration of high-density lipoproteins (HDL).
The hydrochloride salt form of nicardipine, a synthetic derivative of nitrophenyl-pyridine and potent calcium channel blocker, Nicardipine (Nifedipine Family) blocks calcium ions from certain cell walls and inhibits contraction of coronary and peripheral arteries, resulting in lowered oxygen requirements for heart muscle and decreased arterial contraction and spasm. It is used clinically as a cerebral and coronary vasodilator. (NCI04)
The hydrochloride salt form of phenformin, an agent belonging to the biguanide class of antidiabetics with antihyperglycemic activity. Phenformin is not used clinically due to the high risk of lactic acidosis that is associated with its use.
The hydrochloride salt form of thiamine, a vitamin essential for aerobic metabolism, cell growth, transmission of nerve impulses and acetylcholine synthesis. Upon hydrolysis, thiamine hydrochloride is phosphorylated by thiamine diphosphokinase to form active thiamine pyrophosphate (TPP), also known as cocarboxylase. TPP is a coenzyme for many enzymatic activities involving fatty acid, amino acid and carbohydrate metabolism.
The hydrochloride salt form of a metal chelating agent with potential anti-angiogenic activity. Trientine chelates excess copper (Cu) ions in the body; the excess copper is subsequently removed from the body through the kidneys. As Cu is an essential cofactor for cuproenzymes, such as superoxide dismutase 1 (SOD1), depletion of copper may inhibit the activation of signal transduction pathways required for cellular proliferation and angiogenesis. In addition, trientine may inhibit copper-induced secretion of interleukin-8 (IL-8).
A phenylpiperidine with antidiarrheal activity and active metabolite of diphenoxylate. Difenoxin is chemically related to the narcotic opioid meperidine. Difenoxin hydrochloride acts primarily on the gastrointestinal wall by binding to opioid receptors on acetylcholine-containing nerves and inhibits the release of acetylcholine from presynaptic nerve terminals. This leads to a reduction in intestinal motility. Difenoxin hydrochloride also mimics the action of endogenous opioid peptides at the CNS opioid receptors, (primarily mu-receptors), thereby inducing CNS effects.
A preparation of hog pancreatic enzymes standardized for lipase content.
The hydrochloride salt form of anileridine, an opioid receptor agonist belonging to the piperidine class with analgesic activity. By binding to and activating opioid receptors in the central nervous sytem (CNS), anileridine mimics the endogenous opioids resulting in a decrease of nociceptve neurotransmitters and eventually an analgesic effect.
The hydrochloride salt of a natural alkaloid extracted from plants of the genus Pilocarpus with cholinergic agonist activity. As a cholinergic parasympathomimetic agent, pilocarpine predominantly binds to muscarinic receptors, thereby inducing exocrine gland secretion and stimulating smooth muscle in the bronchi, urinary tract, biliary tract, and intestinal tract. When applied topically to the eye, this agent stimulates the sphincter pupillae to contract, resulting in miosis; stimulates the ciliary muscle to contract, resulting in spasm of accomodation; and may cause a transitory rise in intraocular pressure followed by a more persistent fall due to opening of the trabecular meshwork and an increase in the outflow of aqueous humor.
The hydrobromide salt form of homatropine, a synthetic tertiary amine alkaloid with antimuscarinic properties. Homatropine, a competitive inhibitor of acetylcholine at the muscarinic receptor, blocks parasympathetic nerve stimulation. When applied topically to the eye, dilation of the pupil (mydriasis) and paralysis of accommodation (cycloplegia) result from the local anticholinergic effects on the ciliary muscle and iris.
The hydrochloride salt form of protokylol, a derivative of the beta-adrenergic receptor agonist isoproterenol with bronchodilator activity. Protokylol binds to beta-2 adrenergic receptors in bronchial smooth muscle, thereby activating intracellular adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, relieve bronchospasms, improve mucociliary clearance and inhibit the release of mediators of immediate hypersensitivity from cells, especially from mast cells.
Calcitonin (32 aa, ~3 kDa) is encoded by the human CALCA gene. This protein is involved in the modulation of blood calcium and phosphate concentrations through promoting incorporation of these ions into bone.
The sodium salt of hydrocortisone succinate with glucocorticoid property. Hydrocortisone sodium succinate is chemically similar to the endogenous hormone that stimulates anti-inflammatory and immunosuppressive activities, in addition to exhibiting minor mineralocorticoid effects. This agent binds to intracellular glucocorticoid receptors and is translocated into the nucleus, where it initiates the transcription of glucocorticoid-responsive genes, such as various cytokines and lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both potent mediators of inflammation.
An herbal remedy derived from perennial plants of the genus Pulsatilla, a native to central and northern Europe and southern England. The plant contains lactones, saponins, anemone camphor, tannins, and a volatile oil. This remedy has been used traditionally to induce abortions and childbirth.
An herbal extract derived from the root of the plant Glycyrrhiza glabra with potential anti-inflammatory, antioxidant, and antineoplastic activities. Licorice root extract contains glycoside glycyrrhizinic acid and numerous flavonoids. Glycyrrhizinic acid in licorice root extract is hydrolyzed to glycyrrhetic acid (GA); GA inhibits 11 beta-hydroxysteroid dehydrogenase, resulting in inhibition of the conversion of cortisol to the inactive steroid cortisone and elevated cortisol levels. In addition, GA inhibits 17,20-lyase and 17 beta-hydroxysteroid dehydrogenase, resulting in decreased conversions of 17-hydroxyprogesterone to androstenedione and androstenedione to testosterone. The primary antioxidant found in licorice root, the flavonoid glabridin, may inactivate or inhibit the activities of some cytochrome P450 enzymes. In tumor cells, beta-hydroxy-DHP, another flavonoid, may induce Bcl-2 phosphorylation, apoptosis, and G2/M cell cycle arrest.
Vaccines or candidate vaccines used to prevent infection with viruses from the genus SIMPLEXVIRUS. This includes vaccines for HSV-1 and HSV-2.
A live, attenuated measles vaccine with potential antineoplastic activity. Upon subcutaneous administration, live attenuated measles virus vaccine may activate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against measles-positive tumor cells. Measles virus has been shown to be present in some non-small cell lung cancers.
A synthetic vaccine consisting of hemagglutinin (HA) antigens derived from three inactivated influenza viruses, two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine (TIV) is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. Upon administration, the TIV provides active immunization against the three influenza virus strains, thereby protecting against influenza infection. A form of TIV containing higher concentrations of HA antigens may be used in older patients to elicit a more effective immune response.
The hydrochloride salt form of betazole, a histamine H2 receptor agonist with diagnostic application. Betazole selectively targets and binds to the H2 receptor, thereby mimicking the effect of histamine on these receptors. This may lead to an increase in gastric secretions. Betazole can be used in gastric function tests.
The hydrochloride salt of the biguanide metformin with antihyperglycemic and potential antineoplastic activities. Metformin inhibits complex I (NADPH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, thereby increasing the cellular AMP to ATP ratio and leading to activation of AMP-activated protein kinase (AMPK) and regulating AMPK-mediated transcription of target genes. This eventually prevents hepatic gluconeogenesis, enhances insulin sensitivity and fatty acid oxidation and ultimately leads to a decrease in glucose levels. Metformin may exert antineoplastic effects through AMPK-mediated or AMPK-independent inhibition of mammalian target of rapamycin (mTOR), which is up-regulated in many cancer tissues. Furthermore, this agent also inhibits tumor cell migration and invasion by inhibiting matrix metalloproteinase-9 (MMP-9) expression which is mediated through the suppression of transcription activator protein-1 (AP-1) activation.
The hydrochloride salt form of bepridil, a calcium antagonist and class IV anti-arrhythmic agent. Bepridil hydrochloride blocks calcium entry through membranous calcium channels of coronary and peripheral vascular smooth muscle, thereby dilating coronary arteries and peripheral arterioles. This increases oxygen delivery and reduces oxygen requirements. This drug is used to treat chronic stable and variant angina pectoris.
An alpha-1-adrenergic antagonist that acts by blocking alpha-adrenergic receptors in the smooth muscle of blood vessels (arteries, arterioles and veins), gastrointestinal tract, and radial smooth muscle of the iris. This prevents smooth muscle contraction and results in vasodilatation. Administered in the eye, dapiprazole hydrochloride produces miosis. In the heart, it may antagonize alpha-1 adrenoreceptors in myocytes causing a mild negative inotropic effect.
The hydrochloride salt of benazepril, a carboxyl-containing angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, benazepril is metabolized to its active form benazeprilat. Benazeprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II, resulting in vasodilation. Benazeprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
The hydrochloride salt form of quinapril, a prodrug and non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Quinapril is hydrolized into its active form quinaprilat, which binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This abolishes the potent vasoconstrictive actions of angiotensin II and leads to vasodilatation. Quinapril also causes a decrease in angiotensin II-induced aldosterone secretion by the adrenal cortex, thereby promoting diuresis and natriuresis, and increases bradykinin levels.
The root of an herb called Polygala senega. It has been used in some cultures to treat certain medical problems, including problems of the respiratory system.
The hydrochloride salt form of azelastine, a phthalazinone derivative with antihistaminergic activity. Azelastine hydrochloride competes with histamine for the H1 receptor, thereby diminishing the actions of histamine on effector cells and decreasing the histamine-mediated symptoms of allergic reaction, such as bronchoconstriction, vasodilation, increased capillary permeability and spasmodic contractions of gastrointestinal smooth muscle.
The hydrochloride salt form of paroxetine, a phenylpiperidine derivative and a selective serotonin reuptake inhibitor (SSRI) with antidepressant and anxiolytic properties. Paroxetine binds to the pre-synaptic serotonin transporter complex resulting in negative allosteric modulation of the complex thereby blocking reuptake of serotonin by the pre-synaptic transporter. Inhibition of serotonin recycling enhances serotonergic function through serotonin accumulation in the synaptic cleft, resulting in long-term desensitization and downregulation of 5HT1 (serotonin) receptors and leading to symptomatic relief of depressive illness.
A synthetic allylamine derivative structurally related to naftifine, antifungal Terbinafine Hydrochloride blocks ergosterol biosynthesis by inhibition of squalene epoxidase, part of the sterol synthesis pathway for the fungal cell membrane. Highly lipophilic, it tends to accumulate in skin, nails, and fatty tissues. Terbinafine is active against dermatophytes. (NCI04)
A bifunctional alkylating agent and phenylalanine derivative of nitrogen mustard. Melphalan hydrochloride is converted into highly reactive ethylenimmonium intermediates that induce covalent guanine N7-N7 intra- and inter-crosslinks and alkylation of adenine N3 of DNA. This agent also alkylates RNA and protein structures. As a result RNA transcription and protein synthesis are inhibited, ultimately leading to cell growth arrest and/or death.
The hydrochloride salt of a dihydropyridine derivative with diuretic and antihypertensive activity. Cicletanine exerts thiazide-like diuretic activity. In addition, this agent inhibits protein kinase C (PKC) and is able to reverse vasoconstriction through the inhibition of PKC-mediated inhibition of Na/K-ATPase phosphorylation.
Vaccines or candidate vaccines used to prevent infection with Japanese B encephalitis virus (ENCEPHALITIS VIRUS, JAPANESE).
The synthetic dextro isomer of phenylalanine, an essential amino acid with anti-depressant and analgesic activities. D-Phenylalanine is converted into tyrosine and tyrosine in turn is converted into L-dopa, norepinephrine, and epinephrine, three key neurotransmitters. As a result this agent is associated with elevated levels of the neurotransmitters dopamine and norepinephrine in the brain, which may alleviate symptoms of depression. In addition, as an inhibitor of enkephalinase, which metabolizes endorphins, D-phenylalanine may be used to treat chronic pain through blocking the break down of endorphins (natural pain killers).
The hydrochloride salt form of tacrine, an aminoacridine derivative with cognitive stimulating property. Although the mechanism of action has not been fully elucidated, tacrine hydrochloride may bind reversibly to cholinesterase, acetylcholinesterase as well as butyrylcholinesterase, thereby decreasing the breakdown of acetylcholine, and prolonging synaptic actions as well as increased release of acetylcholine. In addition, this agent inhibits monoamine oxidase (MAO) and may inhibit the reuptake of catecholamines and serotonin. Finally, a novel mechanism of action studied in animal models suggests tacrine to attenuate the production of interleukin-1beta in the hippocampus and blood, thereby producing central and peripheral anti-inflammatory effects that may play a role in Alzheimer's disease.
The hydrochloride salt form of levocabastine, a synthetic piperidine derivative with antihistaminic properties. Levocabastine is a second generation histamine-1 receptor antagonist. When applied locally to the eye as a topical solution, this agent reduces itching, rhinorrhea, and symptoms of allergic rhinitis or conjunctivitis.
A cyclohexanol and phenylethylamine derivative that functions as a SEROTONIN AND NORADRENALINE REUPTAKE INHIBITOR (SNRI) and is used as an ANTIDEPRESSIVE AGENT.
Anhydrous from of tacrolimus, a macrolide isolated from Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus possesses similar immunosuppressive properties to cyclosporine, but is more potent.
The hydrochloride salt form of tropisetron, a selective, competitive serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, with antinauseant and antiemetic activities. Tropisetron competitively binds to and blocks the action of serotonin at 5HT3 receptors peripherally on vagus nerve terminals located in the gastrointestinal (GI) tract as well as centrally in the chemoreceptor trigger zone (CTZ) of the area postrema of the central nervous system (CNS). This results in the suppression of chemotherapy- and radiotherapy-induced nausea and vomiting.
The hydrochloride salt form of dorzolamide, an inhibitor of carbonic anhydrase, a zinc-containing enzyme that catalyzes the rapid conversion of carbon dioxide and water into carbonic acid, protons and bicarbonate ions. Distributed throughout many cells and tissues, various carbonic anhydrases play important roles in mineral and metabolic homeostasis. (NCI04)
The hydrochloride salt form of moexipril, a prodrug and non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Moexipril hydrochloride is hydrolized into its active form moexiprilat, which competitively inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the actions of the potent vasoconstrictor angiotensin II and leads to vasodilatation. It also prevents angiotensin II-induced aldosterone secretion by the adrenal cortex, thereby promoting diuresis and natriuresis. Moexipril hydrochloride also directly suppresses renin release.
The hydrochloride salt form of nalmefene, a naltrexone analogue with opioid antagonistic property. Nalmefene antagonizes the effects of opioids by competing for the opioid receptors in the CNS. This results in reversal of the effects of the opioids, including reversal of analgesia, euphoria, respiratory depression, hypotension, sedation and physical dependence.
The hydrochloride salt of valacyclovir. Valacyclovir is an acyclovir prodrug that, after metabolization, inhibits viral DNA replication. It is used in the management of herpes simplex and varicella zoster infections, as well as prophylactically for human cytomegalovirus infections.
A synthetic derivative of phenylpiperazine and chemically unrelated to selective serotonin reuptake inhibitors, tricyclics, tetracyclics, or monoamine oxidase inhibitors (MAOI), antidepressant Nefazadone Hydrochloride antagonizes central 5-HT2 receptors and inhibits reuptake of serotonin and norepinephrine. (NCI04)
A second generation bisphosphonate and synthetic analog of pyrophosphate with anti-bone-resorption activity. Alendronic acid binds to and inhibits the activity of farnesyl pyrophosphate synthetase, an enzyme involved in terpenoid biosynthesis. Inhibition of this enzyme prevents the biosynthesis of isoprenoid lipids, donor substrates of farnesylation and geranylgeranylation during the post-translational modification of small GTPase signalling proteins, which are important in the process of osteoclast turnover. As a result, bone resorption and turnover are reduced.
The sodium salt form of a benzimidazole with selective and irreversible proton pump inhibitor activity. In the acidic compartment of parietal cells, omeprazole is protonated and converted into the active achiral sulfenamide; the active sulfenamide forms one or more covalent disulfide bonds with the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting its activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production. H+/K+ ATPase is an integral membrane protein of the gastric parietal cell.
An herbal remedy containing parts of Leonurus cardiaca, a perennial plant in the mint family Lamiaceae. The parts used are the aerial parts, root, flowers and/or seeds depending on the remedy. The herb contains the alkaloids stachydrine and leonurinine, glycosides, diterpinoids, flavonoids, tannins, volatile oils, and vitamin A.
The anhydrous form of docetaxel, a semisynthetic side-chain analogue of paclitaxel with antineoplastic property. Docetaxel binds specifically to the beta-tubulin subunit of microtubules and thereby antagonizes the disassembly of the microtubule proteins. This results in the persistence of aberrant microtubule structures and results in cell-cycle arrest and subsequent cell death.
The acetate salt of a synthetic cyclic octapeptide analogue of somatostatin. Lanreotide binds to somatostatin receptors (SSTR), specifically SSTR-2 and also to SSTR-5 with a lesser affinity. However, compare with octreotide, this agent is less potent in inhibiting the release of growth hormone from the pituitary gland. Furthermore, lanreotide has an acute effect on decreasing circulating total and free insulin-like growth factor 1 (IGF-I). This agent is usually given as a prolonged-release microparticle or Autogel formulation for the treatment of acromegaly and to relieve the symptoms of neuroendocrine tumors.
An ADRENERGIC BETA-2 RECEPTOR AGONIST with a prolonged duration of action. It is used to manage ASTHMA and in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE.
The hydrochloride salt of an analogue of the antimetabolite nucleoside deoxycytidine with antineoplastic activity. Gemcitabine is converted intracellularly to the active metabolites difluorodeoxycytidine di- and triphosphate (dFdCDP, dFdCTP). dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and apoptosis.
An herb obtained from the plant Harpagophytum procumbens. Devil's claw has been used as a tonic, as a hypoglycemic, to cleanse the lymph system, and in the treatment of arthritis, rheumatism, and skin cancer. This agent may have anti-inflammatory and analgesic properties, possibly due to the presence of antioxidants, phenols, tannins, triterpenoids and volatile oils. (NCI04)
The lithium salt form of benzoic acid with diuretic and urinary antiseptic activity. Lithium benzoate exerts natriuretic activity and disinfects the urinary tract, but has considerable toxicity.
A sodium phosphate salt form of vidarabine, a nucleoside analog with activity against herpes simplex virus and varicella zoster virus. Vidarabine is converted to a monophosphate by viral thymidine kinase and is further modified to a triphosphate form by host enzymes. Vidarabine triphosphate directly inhibits DNA polymerase and also acts as a chain terminator in DNA replication.
An herbal supplement used commonly to alleviate symptoms of benign prostatic hyperplasia. In vitro studies show that it may also have anti-cancer properties specific for prostate cancer.
An herbal product made from the dried root of the several perennial trailing vines of the genus Smilax, native to Central America. Sarsaparilla, used commonly as a flavoring, contains steroidal saponins, numerous phytosterols and flavonoids.
An antibacterial agent used in an aerosol preparation for the treatment of infections of the nose and throat.
A levo isomer of menthol, an organic compound made synthetically or obtained from peppermint or mint oils with flavoring and local anesthetic properties. When added to pharmaceuticals and foods, menthol functions as a fortifier for peppermint flavors. It also has a counterirritant effect on skin and mucous membranes, thereby producing a local analgesic or anesthetic effect.
The sodium salt of a naphthydridine derivative of the broad spectrum, semisynthetic ampicillin with antibacterial activity. Apalcillin specifically binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, thereby preventing the cross-linkage of peptidoglycans, which are critical components of the bacterial cell wall. This leads to a weakening of the bacterial cell wall, eventually causing bacterial cell lysis.
A hydrochloride salt form of tromantadine, a cyclic amine with activity against herpes simplex virus. Tromantadine inhibits absorption of virions to cell surfaces, as well as penetration and uncoating of the virus.
The hydrochloride salt form of tizanidine, an imidazoline derivative structurally similar to clonidine and an adrenergic agonist with muscle relaxant property. Tizanidine stimulates alpha-2 adrenergic receptors in the central nervous system, thereby inhibiting presynaptic release of norepinephrine and increasing the inhibitory effect on alpha motor neurons and motor reflexes. Tizanidine exerts some activity at the postsynaptic excitatory amino acid receptors and imidazoline receptors which may contribute to the overall reduction in facilitation of spinal motor neurons. Overall, tizanidine hydrochloride causes muscle relaxation, reduces spasticity and antinociceptive effects.
The hydrochloride salt form of fexofenadine, a carboxylated metabolic derivative of terfenadine and second generation, long-lasting selective histamine H1 receptor antagonist, with antihistaminic activity. Upon administration, fexofenadine competitively binds of peripheral H1-receptors in the gastrointestinal (GI) tract, blood vessels, and bronchial smooth muscle. This prevents binding of histamine to peripheral H1-receptors and prevents their activation. This prevents a histamine-mediated allergic reaction. Fexofenadine does not cross the blood-brain-barrier (BBB).
The magnesium salt form of a benzimidazole with selective and irreversible proton pump inhibitor activity. In the acidic compartment of parietal cells, omeprazole is protonated and converted into the active achiral sulfenamide; the active sulfenamide forms one or more covalent disulfide bonds with the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting its activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production. H+/K+ ATPase is an integral membrane protein of the gastric parietal cell.
The hydrochloride salt of a guanylhydrazone with potential antineoplastic activity. Mitoguazone competitively inhibits S-adenosyl-L-methionine decarboxylase (SAMD), an enzyme involved in the synthesis of polyamines, resulting in decreased proliferation of tumor cells, antimitochondrial effects, and p53-independent apoptosis. Polyamines, specifically spermine and spermidine, are essential for thymidine kinase production, DNA synthesis, and cell proliferation.
The hydrochloride salt of tamsulosin, a sulfonamide derivative with adrenergic antagonist activity. Tamsulosin selectivity binds to and blocks the activity of alpha1 adrenoreceptors in the human prostate and bladder neck; blockade of these adrenoceptors can cause smooth muscle in the prostate and bladder neck to relax, resulting in an improvement in urinary flow rate.
The anhydrous, sodium salt form of sulfuric acid. Sodium sulfate anhydrous disassociates in water to provide sodium ions and sulfate ions. Sodium ion is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Sodium sulfate anhydrous is an electrolyte replenisher and is used in isosmotic solutions so that administration does not disturb normal electrolyte balance and does not lead to absorption or excretion of water and ions.
The hydrochloride salt of ropivacaine, a local anesthetic of the amide type with analgesic activity. Ropivacaine binds to voltage-gated sodium ion channels in the neuronal membrane, thereby preventing the permeability of sodium ions and resulting in a stabilization of the neuronal membrane and inhibition of depolarization; nerve impulse generation and propagation are blocked, resulting in a reversible loss of sensation.
The hydrochloride salt form of remifentanil, a synthetic anilidopiperidine derivative and short-acting opiate agonist with analgesic and anesthetic properties. Remifentanil selectively binds to and activates the mu-opioid receptor, thereby producing analgesia, respiratory depression, miosis, reduced gastrointestinal motility, and euphoria.
The hydrochloride salt form of ropinirole, a non-ergot dopamine agonist with antiparkinsonian property. Acting as a substitute for dopamine, ropinirole hydrochloride binds to and activates dopamine D2 and D3 receptors within the caudate putamen in the brain, thereby improving motor function.
The hydrochloride salt form of butenafine, a synthetic benzylamine derivative with fungicidal properties. Butenafine hydrochloride interferes with the biosynthesis of ergosterol, an important component of fungal cell membranes, by inhibiting the epoxidation of squalene. This alters fungal membrane permeability and causes growth inhibition. Butenafine hydrochloride is active against a number of dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Sporothrix schenckii, and yeasts, including Candida albicans and C. parapsilosis.
The hydrochloride salt of a piperidine derivative with neurocognitive-enhancing activity. Donepezil reversibly inhibits acetylcholinesterase, thereby blocking the hydrolysis of the neurotransmitter acetylcholine and, consequently, increasing its activity. This agent may improve neurocognitive function in Alzheimer's disease, reduce sedation associated with opioid treatment of cancer pain, and improve neurocognitive function in patients who have received radiation therapy for primary brain tumors or brain metastases.
An antihistamine with mast-cell stabilizing properties used as eye drops in the treatment of ALLERGIC CONJUNCTIVITIS.
The nitrate salt form of sertaconazole, a synthetic imidazole derivative with antifungal property. Sertaconazole nitrate inhibits fungal cytochrome P-450 sterol C-14 alpha-demethylation, resulting in the accumulation of fungal 14 alpha-methyl sterols and the inhibition of ergosterol synthesis, an essential component of the cell membrane of fungi. This leads to a disruption of cell membrane permeability and leakage of adenine triphosphate (ATP) and other constituents from fugal cells.
The hydrochloride salt of a synthetic quinazoline derivative, Anagrelide Hydrochloride reduces platelet production through a decrease in megakaryocyte maturation. Anagrelide inhibits cyclic AMP phosphodiesterase, as well as ADP- and collagen-induced platelet aggregation. At therapeutic doses, it does not influence white cell counts or coagulation parameters. Anagrelide is used for treatment of essential thrombocythemia to reduce elevated platelet counts and the risk of thrombosis. (NCI04)
A group of North American weedy herbs belonging to the genus Solidago (family Asteraceae) with potential chemopreventive activities. Goldenrod may also possess anti-inflammatory, antiseptic properties, diuretic and antifungal properties, and may relieve chemotherapy-induced side-effects.
A magnesium salt formulation of clofibrate, an aryloxyisobutyric acid derivate with antihyperlipidemic activity.
A triterpene-containing herb isolated from the roots and rhizomes of the plant Cimicifuga racemosa (also known as Actaea racemosa). While the mechanism of action of black cohosh is not completely understood, it appears to act as a selective estrogen receptor modulator. In vitro, this preparation has been shown to induce cell cycle arrest and caspase-dependent apoptosis of estrogen-sensitive breast cancer cells. (NCI04)
The hydrochloride salt of nimustine, a nitrosourea with antineoplastic activity. Nimustine alkylates and crosslinks DNA, thereby causing DNA fragmentation, inhibition of protein synthesis, and cell death.
The hydrochloride salt of memantine, a low-affinity, voltage-dependent, noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Memantine binds to and inhibits cation channels of glutamanergic NMDA receptors located in the central nervous system (CNS), preventing the prolonged influx of calcium ions and the associated neuronal excitotoxicity, and thereby potentially enhancing cognitive function. Memantine is also a 5-hydroxytryptamine type 3 (5HT3) receptor and nicotinic receptor antagonist.
The hydrochloride salt form of naratriptan, a sulfonamide with selective serotonin (5-HT) 1 receptor agonistic activity and anti-migraine property. Naratriptan hydrochloride binds selectively and with high affinity to the 5-HT1D and 5-HT1B receptor subtypes. Activation of these 5-HT1D/B receptors located on intracranial blood vessels leads to vasoconstriction and provides relief of migraine headaches. Naratriptan hydrochloride may also exerts its effect by stimulation of 5-HT1D/1B receptors on sensory nerve endings in the trigeminal system thereby decreasing the release of pro-inflammatory neuropeptides.
The hydrochloride salt of pramipexole, a benzothiazole derivative. As a nonergot dopamine agonist, pramipexole binds to D2 and D3 dopamine receptors in the striatum and substantia nigra of the brain. Compared to other dopamine agonists, the use of this agent may be associated with fewer dyskinetic side effects in treated subjects. (NCI04)
A monohalogenated 8-hydroxyquinoline with activity against bacteria, fungi, and protozoa. Cloxyquin is reported to have activity against Mycobacterium tuberculosis, including strains that show resistance to common first-line antibacterial agents.
Glucagon (29 aa, ~3 kDa) is encoded by the human GCG gene. This protein plays a role in the regulation of blood sugar levels through the stimulation of hepatic glycogenolysis and gluconeogenesis.
One of a group of substances that are found in several types of fruit and in milk. They are used in skin care products to reduce wrinkles and soften the skin. Examples of alpha hydroxyl acids are glycolic acid, lactic acid, and citric acid.
A substance derived from the plant Ginkgo biloba. Ginkgo biloba leaf extract contains potent anti-oxidants and substances believed to improve blood flow to the brain and peripheral tissues. Ginkgo biloba exocarp polysaccharides (GBEP) can inhibit proliferation and induce apoptosis and differentiation of tumor cells. As a medicinal herb, ginkgo requires standardization for medicinal use; typically, a 50:1 extract of ginkgo leaf is used in ginkgo supplements. (NCI04)
A nitrogen mustard compound that functions as an ALKYLATING ANTINEOPLASTIC AGENT and is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA and NON-HODGKIN'S LYMPHOMA.
A lipid-soluble azo dye and sulfonamide antibacterial agent.
Having an odor, which often is pleasant or spicy.
The hemihydrate form of estradiol, the most potent, naturally produced estrogen. Estradiol hemihydrate diffuses through the cell membrane and binds to and subsequently activates the nuclear estrogen receptor found in the reproductive tract, breast, pituitary, hypothalamus, liver, and bone. The activated complex binds to the estrogen response element on the DNA and activates the transcription of genes involved in the functioning of the female reproductive system and secondary sex characteristics.
The hydrochloride salt form of tiagabine, a nipecotic acid derivative with anticonvulsant property. Tiagabine hydrochloride inhibits the gamma-aminobutyric acid (GABA) transporter type 1 (GAT1), which is predominantly localized in presynaptic terminals of neurons thereby preventing the reuptake of GABA by the presynaptic endings. Consequently, this increases the level of available GABA within the synaptic cleft, thereby resulting in prolongation of its inhibitory actions. Tiagabine is effective against maximum electroshock seizures and both limbic and generalized tonic-clonic seizures.
The mesylate salt form of eprosartan, a non-biphenyl, non-tetrazole, nonpeptide angiotensin II antagonist with antihypertensive activity. Eprosartan mesylate antagonizes angiotensin II type I receptors in tissues such as vascular smooth muscle and the adrenal gland. This prevents angiotensin II-induced vasoconstriction and prevents angiotensin II-mediated stimulation of aldosterone secretion by the adrenal cortex, which decreases the excretion of sodium and water and increases the excretion of potassium.
The sodium salt form of ibandronic acid, a synthetic nitrogen-containing bisphosphonate. Ibandronic acid inhibits farnesyl pyrophosphate synthase, resulting in a reduction in geranylgeranyl GTPase signaling proteins and apoptosis of osteoclasts. This agent increases bone mineral density, decreases bone remodeling, inhibits osteoclast-mediated bone resorption, and reduces metastases-related and corticosteroid-related bone pain.
A racemic mixture of phenylalanine, an aromatic amino acid with antidepressant, analgesic and appetite suppressant properties. The antidepressant effect of DL-phenylalanine may be accounted for by its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects. This agent also plays a role in alleviating mood swings of premenstrual syndrome (PMS), increasing energy and mental alertness and heighten the ability to focus in individuals with attention deficit hyperactivity disorder (ADHD).
Any synthetic therapeutic agent which is chemically identical to or similar to the endogenous human corticotropin-releasing factor (hCRF). Synthesized in the hypothalamus, hCRF stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH). In cerebral edema, hCRF acts by impeding the flow of fluid from blood vessels into brain tissue, thereby decreasing edema and stabilizing intracranial pressure. This agent possesses anti-edema properties independent of adrenal gland function. (NCI05)
An histamine H1 receptor antagonist without sedative activity. Epinastine hydrochloride blocks the histamine H1 receptor and inhibits the release of histamine from mast cells. This prevents the typical allergic symptoms that are caused by histamine activity on capillaries, skin, mucous membranes, and on gastrointestinal and bronchial smooth muscles. Typical histamine activities include vasodilation, bronchoconstriction, increased vascular permeability, pain, itching, and spasmodic contractions of gastrointestinal smooth muscles. Epinastine also has affinity for the histamine H2, 5-HT2, and the alpha-1, alpha-2 adrenergic receptors.
A thienopyridine with antiplatelet activity. Clopidogrel bisulfate irreversibly alters the platelet receptor for adenosine diphosphate (ADP), thereby blocking the binding of ADP to its receptor, inhibiting ADP-mediated activation of the glycoprotein complex GPIIb/IIIa, and inhibiting fibrinogen binding to platelets and platelet adhesion and aggregation. (NCI04)
A yeast cell-derived recombinant polypeptide related to the naturally occurring, leech-derived anticoagulant hirudin. Lepirudin directly binds to and inactivates thrombin, producing dose-dependent increases in the activated partial thromboplastin time (aPTT) and prothrombin time (PT). The mechanism of action of this agent is independent of antithrombin III and is not inhibited by platelet factor 4. Natural hirudin, a family of highly homologous isopolypeptides, is produced in trace amounts by the leech Hirudo medicinalis.
A vitamin enriched supplement containing higher doses for specific nutrients such as folic acid, intended for women before, during and after pregnancy and also during their lactating phase.
The tartrate salt form of rivastigmine, a phenylcarbamate derivative exhibiting cognitive stimulating property. Although the mechanism of action has not been fully elucidated, rivastigmine tartrate may bind reversibly to cholinesterase, thereby decreasing the breakdown of acetylcholine and enhancing cholinergic function.
The benzoate salt form of rizatriptan, a member of the triptan class agents with anti-migraine property. Rizatriptan benzoate selectively binds to and activates serotonin (5-HT) 1B receptors expressed in intracranial arteries, and to 5-HT 1D receptors located on peripheral trigeminal sensory nerve terminals in the meninges and central terminals in brain stem sensory nuclei. Receptor binding results in constriction of cranial vessels and inhibition of nociceptive transmission, thereby providing relief of migraine headaches. Rizatriptan benzoate may also relief migraine headaches by inhibition of pro-inflammatory neuropeptide release.
Exudate from seeds of the grape plant Vitis vinifera, composed of oils and secondary plant metabolites (BIOFLAVONOIDS and polyphenols) credited with important medicinal properties.
A short-acting sympathomimetic beta-2 adrenergic receptor agonist with bronchodilator activity. Levalbuterol binds to beta-2 adrenergic receptors in bronchial smooth muscle and activates intracellular adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels lead to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation of bronchial smooth muscles. The increased cAMP concentrations also inhibit the release of inflammatory mediators, especially from mast cells.
The hydrochloride salt form of levalbuterol, a relatively selective sympathomimetic beta-2 adrenergic receptor agonist with bronchodilator activity. Levalbuterol hydrochloride binds to beta-2 adrenergic receptors in bronchial smooth muscle and activates intracellular adenyl cyclase, thereby increasing the production of cyclic-3', 5'-adenosine monophosphate (cAMP). Increased cAMP levels lead to the activation of protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in relaxation of bronchial smooth muscles. The increased cyclic AMP concentrations also inhibit the release of inflammatory mediators from mast cells.
The oil extracted from the seeds of Anethum graveolens. Dill seed oil is believed to sooth the nerves and is also used for digestive issues.
An ultra-pure form of water with potential antineoplastic activity. Derived by boiling impure water and condensing the resultant steam in a sterile container, distilled water has been shown to kill bladder cancer cells in vitro through osmotic lysis (cytolysis)
A combination of two synthetic agents with central nervous system stimulant activity. Both agents are non-catecholamine, sympathomimetic agents that elevate blood pressure and cause bronchodilation. These agents are commonly abused psychostimulant drugs that induce psychologic dependence manifested by elevated mood, increased wakefulness, concentration, physical performance and a feeling of well-being. Tolerance to various effects develops unequally, so that tachycardia and enhanced alertness diminish while psychotoxic effects (hallucinations and delusions) may occur. (NCI04)
A supplement containing granules composed of pollen gathered by bees for food and honey. Although the exact composition of nutrients in bee pollen differs depending on various factors, in general it contains important nutrients including vitamins, minerals, amino acids, carotenes, antioxidants, trace elements, carbohydrates as well as other unidentified substances.
A liposomal intrathecal formulation of the antimetabolite cytarabine. As an S-phase-specific antimetabolite, cytarabine is phosphorylated by deoxycytidine kinase to a triphosphate form which competes with thymidine for incorporation into DNA; the incorporation of cytarabine triphosphate into DNA appears to inhibit DNA polymerase and so DNA synthesis, resulting in cell death. (NCI04)
An inactivated virus vaccine that provides active immunization against hepatitis A virus (HAV). Immunization with hepatitis A vaccine induces the formation of anti-HAV antibodies which provide protection against hepatitis A infection.
Human isophane insulin that is used to manage BLOOD GLUCOSE levels in patients with DIABETES.
Regular insulin preparations that contain the HUMAN insulin peptide sequence.
The sodium salt form of a substituted benzimidazole with proton pump inhibitor activity. Pantoprazole is a lipophilic, weak base that crosses the parietal cell membrane and enters the acidic parietal cell canaliculus where it becomes protonated, producing the active metabolite sulfenamide, which forms an irreversible covalent bond with two sites of the H+/K+-ATPase enzyme located on the gastric parietal cell, thereby inhibiting both basal and stimulated gastric acid production.
Human serum-derived alpha-1 proteinase inhibitor (alpha-1-antitrypsin or AAT) with immunomodulating and anti-inflammatory activity. Upon administration, AAT reduces the production of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-32, IL-6, and proteinase 3, and induces the production of anti-inflammatory cytokines, such as IL-10 and the IL-1 receptor antagonist IL-1RN. This agent also downregulates heparan sulfate and reduces the expansion of cytotoxic effector T cells, interferes with the maturation of dendritic cells and increases T regulatory cells. Altogether, AAT may attenuate acute graft-versus-host disease (GvHD) and may facilitate graft acceptance and survival. In addition, AAT enhances levels of cAMP and activation of cAMP-dependent protein kinase A. AAT, a 52kD protein and serine protease inhibitor, belongs to the serpin superfamily.
The maleate salt of rosiglitazone, an orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity. Rosiglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, thereby inducing cell differentiation and inhibiting cell growth and angiogenesis. This agent also modulates the transcription of insulin-responsive genes, inhibits macrophage and monocyte activation, and stimulates adipocyte differentiation.
The hydrochloride salt form of tirofiban, a non-peptide tyrosine derivative with anticoagulant property. Tirofiban antagonizes fibrinogen binding to the platelet cell surface receptor, glycoprotein (GP) IIb/IIIA complex, one of the two purinergic receptors activated by ADP. The antagonism prevents adenylyl cyclase activation, which mediated via GP IIb/IIIa receptor complex, and results in decreased levels of cAMP and thereby interferes with platelet membrane function and subsequent platelet-platelet interaction, release of platelet granule constituents and prolongation of bleeding time.
An herbal extract isolated from the root of the plant Valeriana officinalis with sedative and anxiolytic activities. Valeriana officinalis extract contains four distinct classes of phytochemical constituents: volatile oils; sesquiterpenoids, including valerenic acid and its hydroxyl and acetoxyl derivative; valepotriates; and volatile pyridine alkaloids. Although the exact mechanism of action has not been established, the sesquiterpenoids in Valeriana officinalis extract, particularly valerenic acid, appear to account for its sedative and anxiolytic effects. Valerenic acid is both a subtype-selective GABA-A receptor agonist and a 5HT-5A receptor partial agonist. The sedative-hypnotic benzodiazepines are GABA-A receptor agonists.
von Willebrand factor (2813 aa, ~309 kDa) is encoded by the human VWF gene. This protein is involved in platelet adhesion and blood coagulation.
An omphalocele is an abdominal wall defect limited to an open umbilical ring, and is characterized by the herniation of membrane-covered internal organs into the open base of the umbilical cord. Omphalocele is distinguished from gastroschisis (230750), in which the abdominal wall defect is located laterally to a normally closed umbilical ring with herniation of organs that are uncovered by membranes (summary by Bugge, 2010). On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, Yang et al. (1992) concluded that omphalocele and gastroschisis are casually and pathogenetically distinct abdominal wall defects. Omphalocele can be a feature of genetic disorders, such as Beckwith-Wiedemann syndrome (130650) and the Shprintzen-Goldberg syndrome (182210).
Increase in blood LACTATE concentration often associated with SEPTIC SHOCK; LUNG INJURY; SEPSIS; and DRUG TOXICITY. When hyperlactatemia is associated with low body pH (acidosis) it is LACTIC ACIDOSIS.
Deletion of the short arm of chromosome 1. Common symptoms include mental deficiency, malformed ears, short neck, bulbous nose, heart defects, finger abnormalities, and small deeply set eyes but the phenotype varies with the breakpoint.
Duplication of the long arm of chromosome 1 associated with a variable phenotype, including psychomotor retardation, craniofacial malformations, and various limb, heart, and urogenital anomalies.
Presence of an additional (third) chromosome in an otherwise diploid chromosome complex with variable multiple congenital abnormalities consisting of craniofacial dysmorphism, genital malformation, hand and foot deformities, growth retardation, growth delay, congenital heart defects, and other anomalies.
Duplication of the short arm of chromosome 2 with psychomotor retardation, characteristic facies (prominent forehead, frontal upsweep of hair, hypertelorism, micrognathia, and nose and ear malformations), narrow palate, dolichostenomelia, finger and toe abnormalities, and genital anomalies. Less frequently occurring abnormalities include neural tube defects anencephaly, encephalocele, and spina bifida), bronchial and pulmonary hypoplasia, diaphragmatic hernia, neuroblastoma, a genital anomalies, and congenital heart defects.
Deletion of the long arm of chromosome 2 with a highly variable phenotype marked mainly by low birth weight, delayed somatic and mental development, craniofacial defects (relative small facial features with eye, ear, and nose abnormalities), short neck, finger deformities, heart and lung congenital defects, and other anomalies.
Duplication of the long arm of chromosome 2 with psychomotor retardation and multiple anomalies consisting of unusual facial appearance, clinodactyly, short neck, short toenails, congenital heart defects, anomalies of the genitourinary system, and other abnormalities.
3p deletion syndrome is a condition that results from a chromosomal change in which a small piece of chromosome 3 is deleted in each cell. The deletion occurs at the end of the short (p) arm of the chromosome. This chromosomal change often leads to intellectual disability, developmental delay, and abnormal physical features.Individuals with 3p deletion syndrome typically have severe to profound intellectual disability. Most have delayed development of language skills as well as motor skills such as crawling and walking. While affected individuals learn to walk in childhood, their language ability usually remains limited. Some individuals with 3p deletion syndrome have obsessive-compulsive disorder (OCD) or features of autism spectrum disorders, which are conditions characterized by impaired communication and social interaction.The physical signs and symptoms of 3p deletion syndrome vary greatly. Many affected individuals have slow growth, an abnormally small head (microcephaly), a small jaw (micrognathia), droopy eyelids (ptosis), malformed ears or nose, and widely spaced eyes (hypertelorism). Other frequent features include skin folds covering the inner corner of the eyes (epicanthal folds), extra fingers or toes (polydactyly), and an opening in the roof of the mouth (cleft palate). Additionally, individuals with 3p deletion syndrome may have seizures, weak muscle tone (hypotonia), intestinal abnormalities, or congenital heart defects.
Duplication of the short arm of chromosome 3 with severe delay in mental development, craniofacial dysmorphism, urogenital maldevelopment, and various occasional anomalies, including cardiac defects, cleft lip and palate, holoprosencephaly, dermatoglyphic findings, and other malformations.
Duplication of the long arm of chromosome 3 with psychomotor retardation, characteristic facies, congenital heart anomalies, abnormal dermatoglyphic patterns, skeletal defects, and other abnormalities. The syndrome was first reported as familial de Lange syndrome (1) with chromosomal abnormalities. Manifestations of dup(3q) are similar to those in de Lange syndrome. Intrauterine growth retardation, prominent philtrum, proximally placed thumbs, oligodactyly, and phocomelia are more frequent in de Lange syndrome, whereas craniosynostosis, cleft palate, and urinary tract anomalies are more common in dup(3q).
Duplication of the long arm of chromosome 4 with delayed development, craniofacial abnormalities, limb defects, and variable neurological, ophthalmological, urogenital and other anomalies.
A rare chromosomal anomaly syndrome with variable phenotype and principle characteristics of developmental delay, growth retardation/short stature, hypotonia, seizures, ventriculomegaly, hand and foot anomalies (for example clinodactyly, overlapping toes) and mosaic pigmentary skin changes. Patients may also present minor dysmorphic craniofacial features (including macrocephaly, upslanting palpebral fissures, hypertelorism, abnormal auricles, anteverted nasal tip, midface hypoplasia).
A rare chromosomal anomaly syndrome with a highly variable phenotype. Principle characteristics are prenatal/postnatal growth failure, intellectual disability, developmental delay, craniofacial dysmorphism (including microcephaly, microphthalmia, epicanthus, low-set and malformed ears, broad and flat nasal bridge, full lips, micrognathia), central nervous system anomalies (for example hydrocephalus, cortical atrophy, ventriculomegaly), short neck, and delayed bone age. Cardiac defects, limb anomalies, hip joint malformations and seizures have also been reported.
Deletion of the long arm of chromosome 6 with delayed mental development and variable multiple abnormalities, mainly microcephaly, orofacial anomalies, short neck, cardiovascular defects, abnormal dermatoglyphics, hand deformities, and other defects.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 6. The disorder has a highly variable phenotype with typical characteristics of growth and developmental delay, intellectual disability, craniofacial dysmorphism (microcephaly, flat facial profile, frontal bossing, hypertelorism, downward-slanting palpebral fissures, flat nasal bridge, anteverted nares, bow shaped mouth, micrognathia), short webbed neck and joint contractures. Cardiac, urogenital, ophthalmologic and hand and foot anomalies, as well as umbilical hernia, spasticity and seizures are other features that have been reported.
A rare chromosomal anomaly syndrome with a highly variable phenotype. Principle characteristics are growth failure, short stature, intellectual disability, dermatological abnormalities (naevus flammeus, dark pigmented naevi, cafe au lait spots), microcephaly and facial dysmorphism (including facial asymmetry, small ears, abnormal palpebral fissures, ptosis, epicanthic folds, hyper/hypotelorism). Additional reported features include convulsions, cleft lip and palate, clinodactyly, kyphoscoliosis and genital anomalies (cryptorchidism, hypospadias, micropenis).
Duplication of the short arm of chromosome 7. Clinical manifestations vary with the size of duplication and the involvement of additional chromosomes and usually include mental retardation, dolichocephaly, micrognathia, upslanting palpebral fissures, low-set malformed ears, abnormal dermatoglyphics, and other anomalies.
Duplication of the long arm of chromosome 7 with multiple abnormalities and delayed mental and physical development. Infants with dup(7)(q31-7qter) have large fontanels, prominent forehead, short downslanting palpebral fissures, long philtrum, thin vermilion border, downcurved upper lip, and micrognathia; those with dup(7)(q32-7qter) also have hypotonia, epicanthal folds, scoliosis, hip dislocation, and strabismus; and patients with inv dup(7)(q21.2-q36) have hydrocephalus, depressed nasal bridge, low-set ears, microretrognathia, and short neck. The phenotype varies with the size of the duplicated segment. Duplication of large segments usually results in early mortality.
Recombinant 8 syndrome is a condition that involves heart and urinary tract abnormalities, moderate to severe intellectual disability, and a distinctive facial appearance. The characteristic facial features include a wide, square face; a thin upper lip; a downturned mouth; a small chin (micrognathia); wide-set eyes (hypertelorism); and low-set or unusually shaped ears. People with recombinant 8 syndrome may have overgrowth of the gums (gingival hyperplasia) and abnormal tooth development. Males with this condition frequently have undescended testes (cryptorchidism). Some affected individuals have recurrent ear infections (otitis media) or hearing loss. Many children with recombinant 8 syndrome do not survive past early childhood, usually due to complications related to their heart abnormalities.
Deletion of the short arm of chromosome 8 postnatal growth retardation, microcephaly, subnormal mentality, epicanthal folds, malformed ears, brevicollis, widely spread nipples, heart defects, and other abnormalities. Congenital spherocytic anemia may occur.
A rare chromosomal anomaly syndrome, resulting from the partial duplication of the short arm of chromosome 8. The disease has a highly variable phenotype ranging from no dysmorphic features and only mild intellectual disability to patients with severe developmental delay, neonatal hypotonia, short stature, profound intellectual disability, mild dysmorphic features (for example mild ptosis, hypertelorism, down-slanting palpebral fissures, broad nasal bridge, short, prominent philtrum, abnormal dentition) and structural brain abnormalities. Autism, epilepsy, and spastic paraplegia have also been reported.
Deletion of the long arm of chromosome 8 with craniofacial abnormalities (microcephaly, midfacial hypoplasia, and prominent forehead), psychomotor retardation, and various eye, nose, ear, heart, and skeletal abnormalities. The phenotype and severity of symptoms vary with the type of deletion. Interstitial deletions 8q may be associated with several syndromes, including the tricho-rhino-phalangeal syndromes I and II (Langer-Giedion syndrome).
Duplication of the long arm of chromosome 8. The most commonly associated abnormalities include low birth weight, mental deficiency, prominent forehead, flat occiput, hypertelorism, upslanting palpebral fissures, ear and nose deformities, thin upper lips, and skeletal defects. The phenotype varies in relation to the type of duplication.
Partial deletion of the short arm of chromosome 9 with mental retardation, craniofacial anomalies, abnormal dermatoglyphics, short and webbed neck, heart murmurs, square nails, and other defects.
Partial tetrasomy involving the short arm of chromosome 9 with psychomotor retardation and variable multiple craniofacial, skeletal, cardiovascular, and urogenital abnormalities.
Kleefstra syndrome is characterized by intellectual disability, autistic-like features, childhood hypotonia, and distinctive facial features. The majority of individuals function in the moderate-to-severe spectrum of intellectual disability although a few individuals have mild delay and total IQ within low-normal range. While most have severe expressive speech delay with little speech development, general language development is usually at a higher level, making nonverbal communication possible. A complex pattern of other findings can also be observed; these include heart defects, renal/urologic defects, genital defects in males, severe respiratory infections, epilepsy/febrile seizures, psychiatric disorders, and extreme apathy or catatonic-like features after puberty.
Duplication of the long arm of chromosome 9 with psychomotor retardation, deeply-set eyes, microdolichocephaly, beaked nose, and microretrognathia. Depending on the length of the deleted segment, additional features may include small mouth, large ears, finger abnormalities, limited joint movement, failure to thrive, congenital heart defects, and other anomalies. Longer deletions are more likely to develop life-threatening malformations shorter ones. 9q34 is sometimes considered as a separate entity which is characterized by slight psychomotor retardation, limited speech capacity, hyperactivity, feeding difficulty, failure to thrive, joint contractures, finger abnormalities, erythema, heart murmur, blepharoptosis, strabismus, dolichocephaly, facial asymmetry, narrow palpebral fissures, microphthalmia, and downturned corners of the mouth.
Deletion of the short arm of chromosome 10 with retarded psychomotor development and variable abnormalities, including dwarfism, craniofacial dysmorphism (downslanting palpebral fissures, anteverted nostrils, and eye and ear anomalies), deformed hands and feet, cryptorchidism, and dysplasia of the olfactory system.
Deletion of the long arm of chromosome 10 with delayed physical and mental development and relatively nonspecific variable abnormalities. The phenotype varies in relation to the type of deletion. The most frequent abnormalities which are common to all types include microcephaly, congenital heart defects, and hypotonia. Terminal deletion is usually characterized by anoxia and respiratory distress at birth, frequent prematurity, malformed ears, prominent nose, hypertelorism, strabismus, and short or webbed neck. Patients with ring chromosome 10 usually have hydronephrosis, bladder obstruction, cryptorchidism, and hypoplastic scrotum.
Duplication of the long arm of chromosome 10 with cardiac, renal, and respiratory complications, orofacial dysmorphism, and psychomotor retardation which vary with different karyotypes.
Jacobsen syndrome is a condition caused by a loss of genetic material from chromosome 11. Because this deletion occurs at the end (terminus) of the long (q) arm of chromosome 11, Jacobsen syndrome is also known as 11q terminal deletion disorder.The signs and symptoms of Jacobsen syndrome vary considerably. Most affected individuals have delayed development, including the development of speech and motor skills (such as sitting, standing, and walking). Most also have cognitive impairment and learning difficulties. Behavioral problems have been reported, including compulsive behavior (such as shredding paper), a short attention span, and easy distractibility. Many people with Jacobsen syndrome have been diagnosed with attention deficit-hyperactivity disorder (ADHD). Jacobsen syndrome is also associated with an increased likelihood of autism spectrum disorders, which are characterized by impaired communication and socialization skills.Jacobsen syndrome is also characterized by distinctive facial features. These include small and low-set ears, widely set eyes (hypertelorism) with droopy eyelids (ptosis), skin folds covering the inner corner of the eyes (epicanthal folds), a broad nasal bridge, downturned corners of the mouth, a thin upper lip, and a small lower jaw. Affected individuals often have a large head size (macrocephaly) and a skull abnormality called trigonocephaly, which gives the forehead a pointed appearance.More than 90 percent of people with Jacobsen syndrome have a bleeding disorder called Paris-Trousseau syndrome. This condition causes a lifelong risk of abnormal bleeding and easy bruising. Paris-Trousseau syndrome is a disorder of platelets, which are blood cell fragments that are necessary for blood clotting.Other features of Jacobsen syndrome can include heart defects, feeding difficulties in infancy, short stature, frequent ear and sinus infections, and skeletal abnormalities. The disorder can also affect the digestive system, kidneys, and genitalia. The life expectancy of people with Jacobsen syndrome is unknown, although affected individuals have lived into adulthood.
Duplication of the long arm of chromosome 11 with delayed growth and mental development, craniofacial asymmetry, microcephaly, dysmorphic facies, strabismus, musculoskeletal abnormalities, imperforate anus, cryptorchidism, and congenital heart defects. Some patients exhibits symptoms of cri-du-chat or chromosome 5p deletion syndrome (a peculiar crying sound resembling that of a suffering kitten observed in infants with craniofacial abnormalities that include microcephaly, round facies, hypertelorism, upslanting palpebral fissures, epicanthus, large frontal sinus, and other anomalies). The phenotype is variable and is related to the size of duplication. Mental retardation ranges from moderate to severe.
An abnormality in which both ends of a chromosome have been lost (deletion) and the two broken ends reunited to form a ring-shaped figure. Abnormalities include short stature, microcephaly, mental deficiency, characteristic facies, highly arched palate, clinodactyly, and other defects.
Deletion of the short arm of chromosome 12. The syndrome is relatively rare and has a variable phenotype, consisting of growth and mental retardation and various craniofacial, neurological, and other abnormalities.
Duplication of the short arm of chromosome 12 with multiple congenital abnormalities consisting of characteristic facies, increased birth weight, severe psychomotor retardation, and occasional postpartum asphyxia. Additional findings may include turricephaly, high forehead, everted lower lip, ear abnormalities, foot deformities, accessory nipples and, less frequently, congenital heart defects, anal atresia, and other anomalies.
Duplication of the long arm of chromosome 12 with craniofacial, skeletal, and cardiovascular abnormalities, sacral dimple, simian creases, and psychomotor retardation.
A chromosomal anomaly of chromosome 13 with characteristics of a widely variable phenotype ranging from mild to severe. Principle manifestations include intrauterine growth retardation, developmental delay, short stature, moderate to severe intellectual deficit, microcephaly, facial dysmorphism (i.e. up-slanting palpebral fissures, hypertelorism, abnormal ears, broad nasal bridge, high arched palate, micrognathia, small mouth, and thin lips), hands and feet anomalies and genital abnormalities.
Cutis verticis gyrata, hypoplastic thyroid disease and mental retardation.
Duplication of the long arm of chromosome 13 with retarded development and craniofacial, neurological, and other abnormalities.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 14 in somatic cells.
A rare chromosomal anomaly syndrome with a highly variable phenotype. The syndrome has characteristics of pre and/or postnatal growth retardation, variable intellectual disability, short stature, dysmorphic features (microcephaly, triangular facies, frontal bossing, hypertelorism, ear anomaly, broad nasal bridge, highly arched palate, micrognathism), hand and feet anomalies (e.g. brachydactyly, clinodactyly, syndactyly), and multiple hyperpigmented and/or hypopigmented spots. Severe phenotypes present with cardiac abnormalities and/or renal malformations. Other reported features include hypotonia, speech delay, talipes equinovarus, and genital anomalies (cryptorchidism and hypospadias).
A chromosomal abnormality consisting of the presence of a third copy of chromosome 15 in somatic cells.
Duplication of the long arm of chromosome 15. Some cases have symptoms which are similar to those in Prader-Willi and Angelman syndromes but most exhibit a wide spectrum of manifestations which range from asymptomatic cases to variable combinations of skeletal, neurological, gastrointestinal, psychological, and other abnormalities in association with developmental delay. Phenotypic expression and degree of severe are related to the length of the duplicated segment.
A rare chromosomal aberration characterized by presence of two additional copies of a fragment of the long arms in an otherwise diploid chromosome 15 occurring in association with multiple abnormalities, including metopic craniosynostosis, facial anomalies, cranial asymmetry, atrio-septal defects, hydronephrosis, flexion contractures of the lower limbs, mental retardation, sensorineural hearing loss, and mental retardation.
Duplication of the short arm of chromosome 16 with severe psychomotor delay, rounded face, sparse hair, malformed ears, hypertelorism, cleft palate, a thin upper lip, and renal dysgenesis. The severity of expression varies with the type of duplication. Spontaneous abortion usually takes place in severe cases and about 50% die in infancy.
Deletion of the long arm of chromosome 16 characterized mainly by developmental delay, craniofacial anomalies, feeding difficulties, failure to thrive, hypotonia, and other disorders. The phenotype varies with the breakpoints.
Smith-Magenis syndrome (SMS) is characterized by distinctive physical features (particularly facial features that progress with age), developmental delay, cognitive impairment, and behavioral abnormalities. Infants have feeding difficulties, failure to thrive, hypotonia, hyporeflexia, prolonged napping or need to be awakened for feeds, and generalized lethargy. The majority of individuals function in the mild-to-moderate range of intellectual disability. The behavioral phenotype, including significant sleep disturbance, stereotypies, and maladaptive and self-injurious behaviors, is generally not recognized until age 18 months or older and continues to change until adulthood. Sensory integration issues are frequently noted. Children and adults typically have inattention, distractibility, hyperactivity, impulsivity, maladaptive behaviors including frequent outbursts/temper tantrums, attention seeking, disobedience, aggression, toileting difficulties, and self-injurious behaviors (SIB) including self-hitting, self-biting, and/or skin picking, inserting foreign objects into body orifices (polyembolokoilamania), and yanking fingernails and/or toenails (onychotillomania). Among the stereotypic behaviors described, the spasmodic upper-body squeeze or ""self-hug"" seems to be highly associated with SMS. The finger lick and page flipping (""lick and flip"") behavior may be less prevalent than initially reported. An underlying developmental asynchrony, specifically between intellectual functioning and emotional maturity, may also contribute to maladaptive behaviors in people with SMS.
A rare chromosomal abnormality resulting from the duplication of the short arm of chromosome 17 with characteristics of pre and post-natal growth retardation, developmental delay, hypotonia, digital abnormalities, congenital heart defects, and distinctive facial features. It has been described in fewer than 15 patients. Facial dysmorphism includes microcephaly, receding forehead, down-slanting palpebral fissures, ptosis, hypertelorism, low-set malformed ears, smooth philtrum, micrognathia, high-arched palate and a short broad neck. Digital abnormalities include absent fourth and fifth digits, brachydactyly and fifth finger clinodactyly. Genital hypoplasia in males and hypertrichosis are often observed. Intellectual deficit is severe to profound and the prognosis is poor. Trisomy 17p has been reported to be pure, as the result of a de novo 17p duplication or an extra chromosome derived from the 17p arm.
Tetrasomy 18p is a chromosomal condition that affects many parts of the body. This condition usually causes feeding difficulties in infancy, delayed development, intellectual disability that is often mild to moderate but can be severe, changes in muscle tone, distinctive facial features, and other birth defects. However, the signs and symptoms vary among affected individuals.Babies with tetrasomy 18p often have trouble feeding and may vomit frequently, which makes it difficult for them to gain weight. Some affected infants also have breathing problems and jaundice, which is a yellowing of the skin and the whites of the eyes.Changes in muscle tone are commonly seen with tetrasomy 18p. Some affected children have weak muscle tone (hypotonia), while others have increased muscle tone (hypertonia) and stiffness (spasticity). These changes contribute to delayed development of motor skills, including sitting, crawling, and walking.Tetrasomy 18p is associated with a distinctive facial appearance that can include unusually shaped and low-set ears, a small mouth, a flat area between the upper lip and the nose (philtrum), and a thin upper lip. Many affected individuals also have a high, arched roof of the mouth (palate), and a few have had a split in the roof of the mouth (cleft palate).Additional features of tetrasomy 18p can include seizures, vision problems, recurrent ear infections, mild to moderate hearing loss, constipation and other gastrointestinal problems, abnormal curvature of the spine (scoliosis or kyphosis), a shortage of growth hormone, and birth defects affecting the heart and other organs. Males with tetrasomy 18p may be born with undescended testes (cryptorchidism) or the opening of the urethra on the underside of the penis (hypospadias). Psychiatric conditions, such as attention deficit hyperactivity disorder (ADHD) and anxiety, as well as social and behavioral challenges have also been reported in some people with tetrasomy 18p.
A rare chromosomal anomaly syndrome with a highly variable phenotype that may range from normal to patients with profound intellectual disability, developmental delay, learning disability (especially speech) and mild dysmorphism (including micro/macrocephaly, prominent forehead, low-set and posteriorly rotated ears, hypertelorism, high nasal bridge, prominent philtrum, retro/micrognathia). Mild hypotonia and autistic-like mannerisms (for example hand opening and closing, head banging) may also be associated. Other anomalies, such as cutis laxa, hearing loss, syndactyly, digital hypoplasia and talipes equinovarus have also been reported.
Duplication of the long arm of chromosome 19 with psychomotor retardation, microbrachycephaly, open cranial sutures, downslanting palpebral fissures, blepharoptosis, hypertelorism, downturned corners of the mouth, and short nose. The severity of symptoms is related to the length of the duplicated segment.
This syndrome has characteristics of moderate intellectual deficit and severe, early-onset retinitis pigmentosa. It has been described in five males spanning three generations of one family. Some patients also had microcephaly. It is transmitted as an X-linked recessive trait.
The absence of one chromosome of one pair in an otherwise diploid chromosome 21. The syndrome is characterized by developmental retardation in association with craniofacial, skeletal, genital, cardiac, and other anomalies. The phenotype shares some similarities with the chromosome 21q deletion syndrome.
Partial tetrasomy involving the long arm of chromosome 21 with mental retardation, craniofacial dysmorphism, hernia, genital anomalies, and hand and foot deformities.
Absence of one chromosome of one pair in an otherwise diploid cell of chromosome 22 associated with psychomotor retardation and multiple orofacial, digital, and other congenital anomalies.
A frequently lethal ploidy syndrome marked by the presence of four sets of chromosomes (92,XXYY or 92,XXXX) usually resulting in spontaneous abortions. Infants who survive usually exhibit mental retardation and multiple craniofacial, limb, cardiovascular, renal, and other variable malformations.
Infantile or complex glycerol kinase deficiency is a contiguous gene syndrome caused by microdeletion of GK (300474) and its neighboring genes, dystrophin (300377), which causes Duchenne muscular dystrophy (DMD; 310200), and NR0B1 (300473), which causes congenital adrenal hypoplasia (AHC; 300200). Patients present with hyperglycerolemia and glyceroluria, associated with DMD and/or AHC (summary by Stanczak et al., 2007).
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypical, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options.
MCT8-specific thyroid hormone cell-membrane transporter deficiency is characterized by severe cognitive deficiency, infantile hypotonia, diminished muscle mass and generalized muscle weakness, progressive spastic quadriplegia, joint contractures, and dystonic and/or athetoid movement with characteristic paroxysms or kinesigenic dyskinesias. Seizures occur in about 25% of cases. Most affected males never sit or walk independently or lose these abilities over time; most never speak or have severely dysarthric speech. Brain MRI obtained in the first few years of life shows transient delayed myelination, which improves by age four years. Although psychomotor findings observed in affected males do not occur in heterozygous females, the latter often have thyroid test abnormalities intermediate between affected and normal individuals.
Duplication of the long arm of chromosome X with growth retardation, developmental delays, seizures, behavioral problems, gonadal dysgenesis, and symptoms of Ullrich-Turner XO syndrome, a syndrome wherein the affected patients have only 45 chromosomes producing an XO chromosome constitution, occurring with webbed neck, cubitus valgus, shield chest, short stature, lymphedema, coarctation of the aorta, pigmented nevi, and other anomalies.
A syndrome of total absence of hair, extreme growth failure, mental retardation, and multiple craniofacial, skeletal, and other abnormalities.
Syngnathia refers to congenital fusion of the maxilla and mandible. The fusion can be classified depending on the nature of the connecting tissue as either fibrous or bony fusion. Laster et al. (2001) proposed a classification for bony syngnathia into 4 types. Type 1a is simple anterior syngnathia characterized by bony fusion of the alveolar ridge only; type 1b is complex anterior syngnathia characterized by bony fusion of the alveolar ridges and also associated with other congenital malformations in the head and neck region; type 2a is simple mandibulozygomatic syngnathia characterized by bony fusion of the mandible to zygoma; and type 2b is complex mandibulozygomatic syngnathia characterized by bony fusion of the mandible to the zygoma and associated with cleft palate and/or temporomandibular joint ankylosis.
A syndrome of spastic dwarfism with prominent eyes associated with retarded bone age, delayed mental development, small size at birth and during early childhood, slender build, spasticity, convulsions, and characteristic facies.
Uveal coloboma-cleft lip and palate-intellectual disability is characterised by coloboma of the iris, bilateral cleft lip and palate, and intellectual deficiency of varying degree. A wide variability in clinical expression is observed. Some patients also present with microphthalmia, cataract, glaucoma, ptosis, sensorineural hearing loss and haematuria. To date, 12 cases have been described from three generations of a single family. Transmission is autosomal dominant.
Cantú syndrome and the related disorders acromegaloid facial appearance (AFA) and hypertrichosis and acromegaloid facial features (HAFF) are characterized by congenital hypertrichosis; distinctive coarse facial features (including broad nasal bridge, wide mouth with full lips and macroglossia); enlarged heart (increased ventricular mass, enlarged chambers, and normal cardiac function); and skeletal abnormalities (thickening of the calvaria, broad ribs, scoliosis, and flaring of the metaphyses). Other cardiovascular abnormalities may include patent ductus arteriosus (PDA) (in 50%), pericardial effusion (20%), and increased vascular tortuosity. Intellect is typically normal; behavioral problems can include anxiety, mood swings, obsessive-compulsive disorder, and tics.
A syndrome of dysmorphic facies and conotruncal heart defects having common genetic characteristics with DiGeorge and Shprinzen syndromes. Considered a variant of the CATCH 22 syndrome.
Cowchock syndrome (COWCK) is an X-linked recessive neuromuscular disorder characterized by early childhood onset of a slowly progressive axonal sensorimotor neuropathy associated in some patients with sensorineural deafness and cognitive impairment (summary by Rinaldi et al., 2012).
A lethal combination of manifestations including short stature, congenital cataracts, encephalopathy with epileptic fits and postmortem confirmation of nephropathy (renal tubular necrosis). The combination has been described in 2 female infant children of first cousin parents. The infants did not survive beyond 4 and 8 months respectively. There have been no further descriptions in the literature since 1963.
Curry-Jones syndrome is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas (summary by Twigg et al., 2016).
Alpha-thalassemia X-linked intellectual disability (ATRX) syndrome is characterized by distinctive craniofacial features, genital anomalies, severe developmental delays, hypotonia, intellectual disability, and mild-to-moderate anemia secondary to alpha-thalassemia. Craniofacial abnormalities include small head circumference, telecanthus or widely spaced eyes, short nose, tented vermilion of the upper lip, and thick or everted vermilion of the lower lip with coarsening of the facial features over time. Although all affected individuals have a normal 46,XY karyotype, genital anomalies range from hypospadias and undescended testicles to severe hypospadias and ambiguous genitalia, to normal-appearing female external genitalia. Global developmental delays are evident in infancy and some affected individuals never walk independently or develop significant speech.
DOORS syndrome (also known as DOOR syndrome) is a multiple congenital anomalies-intellectual disability syndrome characterized by sensorineural hearing loss (deafness), onychodystrophy, osteodystrophy, mild to profound intellectual disability, and seizures.
A syndrome reported in an Edinburgh family in which five infants (four female and one male) were found to have a characteristic facial appearance, hydrocephalus, and psychomotor retardation. Some characteristics of this syndrome are similar to those of the de Lange syndrome 1.
A multiple congenital anomalies, intellectual disability syndrome with characteristics of sensorineural hearing loss, onychodystrophy, osteodystrophy, mild to profound intellectual disability and seizures. About 50 cases have been reported to date. Caused by mutations in the TBC1D24 gene (16p13.3) encoding a protein involved in the regulation of membrane trafficking. Inherited autosomal recessively.
A very rare syndrome with characteristics of intellectual deficit, horseshoe kidney, and congenital heart defects. Four cases have been reported in the literature in two unrelated families. Dysmorphic features include plagiocephaly, malar hypoplasia, broad nasal bridge, poorly developed philtrum and nasal alae, cleft palate and hypodontia. Congenital heart defects were endocardial fibroelastosis in one family and prolapse of the tricuspid valve in the other. The condition is probably hereditary and transmitted as an autosomal recessive trait.
The pseudoaminopterin syndrome (aminopterin syndrome sine aminopterin; ASSA) is a multiple congenital anomaly disorder characterized by ossification defects of the skull, dysmorphic facial features, delayed development, and variable limb defects. The clinical features resemble the embryopathy caused by maternal treatment with the folic acid antagonist aminopterin, which has been recognized since 1952 (Thiersch, 1952) when aminopterin was used as an abortifacient. The characteristic phenotype of the children who survived infancy after having been exposed to aminopterin or its methyl derivative, methotrexate, in early pregnancy included a very unusual facies, skull anomalies, and skeletal defects (summary by Fraser et al., 1987).
Filippi syndrome is characterized by short stature, microcephaly, syndactyly, intellectual disability, and facial dysmorphism consisting of bulging forehead, broad and prominent nasal bridge, and diminished alar flare. Common features include cryptorchidism, speech impairment, and clinodactyly of the fifth finger, Some patients exhibit visual disturbances, polydactyly, seizures, and/or ectodermal abnormalities, such as nail hypoplasia, long eyelashes, hirsutism, and microdontia (summary by Hussain et al., 2014).
Syndrome with characteristics of psychomotor delay, brachycephaly with flat face, small nose, microstomia, cleft palate, cataract, hearing loss, hypoplastic scrotum and digital anomalies. Less than 10 patients have been described in the literature so far. Although the majority of reported cases were sporadic, the syndrome has been reported in one pair of siblings (a brother and sister) with an apparently autosomal recessive inheritance pattern.
This syndrome is characterized by slowly progressive spastic paraplegia, skeletal anomalies of the hands and feet with brachydactyly type E, cone-shaped epiphyses, abnormal metaphyseal phalangeal pattern profile, sternal anomaly (pectus carinatum or excavatum), dysarthria, and mild intellectual deficit. It has been reported in five patients, among which there were two sets of identical twins. The significance of the relationship between the twinning process and the condition is not clear. The mode of inheritance is unknown but single-gene transmission seems likely.
An extremely rare multi-systemic genetic disorder with characteristics of intellectual disability, deafness, skeletal abnormalities and coarse facial features.The syndrome is exceedingly rare and has been reported in only a few patients to date. Male and female patients have been described. The main clinical features include moderate to severe intellectual deficit, congenital sensorineural hearing impairment and broad, stubby hands and feet. A coarse face with full lips and cheeks is also found. These signs are reported to become more prominent with age. The pattern of inheritance appears to be autosomal recessive.
Mental and somatic retardation with Peters anomaly (defect of the Descemet membrane and deep stromal layers of the cornea), corneal clouding, hypoplastic facies, subvalvular aortic stenosis, and skeletal abnormalities.
Galloway-Mowat syndrome is a rare autosomal recessive neurodegenerative disorder characterized by infantile onset of microcephaly and central nervous system abnormalities resulting in severely delayed psychomotor development. Brain imaging shows cerebellar atrophy and sometimes cerebral atrophy. More variable features include optic atrophy, movement disorders, seizures, and nephrotic syndrome (summary by Vodopiutz et al., 2015). Genetic Heterogeneity of Galloway-Mowat Syndrome See also GAMOS2 (301006), caused by mutation in the LAGE3 gene (300060) on chromosome Xq28; GAMOS3 (617729), caused by mutation in the OSGEP gene (610107) on chromosome 14q11; GAMOS4 (617730), caused by mutation in the TP53RK gene (608679) on chromosome 20q13; GAMOS5 (617731), caused by mutation in the TPRKB gene (608680) on chromosome 2p13; GAMOS6 (618347), caused by mutation in the WDR4 gene (605924) on chromosome 21q22; GAMOS7 (618348), caused by mutation in the NUP107 gene (607617) on chromosome 12q15; and GAMOS8 (618349), caused by mutation in the NUP133 gene (607613) on chromosome 1q42.
Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), a neurodevelopmental and neurodegenerative disorder, is characterized by severe progressive sensorimotor neuropathy with resulting hypotonia, areflexia, and amyotrophy and variable degrees of dysgenesis of the corpus callosum. Mild-to-severe intellectual disability and ""psychotic episodes"" during adolescence are observed. Sensory modalities are moderately to severely affected beginning in infancy. The average age of onset of walking is 3.8 years; the average age of loss of walking is 13.8 years; the average age of death is 33 years.
Anomalies of the prosencephalic structures, atelencephaly, and microcephaly in association with congenital heart diseases, preaxial limb malformations, eye abnormalities, and genital and other deformities. The disorder is frequently lethal. Infants who survive are severely retarded. Ring chromosome 13, duplication of the long arm of chromosome 13, and this syndrome share many common clinical features. In the synonym XK syndrome, the letter ""X"" stands for the unreported name of the patient of Garcia and Duncan, and ""K"" for the initial of Lurie's patient.
Chylomicron retention disease is an autosomal recessive disorder of severe fat malabsorption associated with failure to thrive in infancy (Dannoura et al., 1999).
Gomez-Lopez-Hernandez syndrome, also known as cerebellotrigeminal dermal dysplasia, is a rare neurocutaneous syndrome classically characterized by the triad of rhombencephalosynapsis, trigeminal anesthesia, often giving rise to corneal opacities, and bilateral parietal or parietooccipital alopecia, However, trigeminal anesthesia is an inconsistent finding (summary by Sukhudyan et al., 2010).
Mental retardation syndrome with microcephaly, severely impaired vision, hearing defect, epileptic seizures, restricted movement, and early death.
A very rare syndrome consisting of microcephaly with facial dysmorphism, spondylometaphyseal dysplasia and severe intellectual deficit. Eight cases have been reported in the literature in two unrelated families. Dysmorphic features include hypertelorism, depressed nasal bridge, and large nose with a large nasal tip, anteverted nostrils and wide mouth with thick lips. Affected patients do not achieve language ability. The condition is probably hereditary, and transmitted as an autosomal recessive trait.
A syndrome of multiple congenital malformations with an association of cleft lip and palate, patchy pigmentary retinopathy (cat's paw), obstructive liver disease (cholestasis, portal hypertension) and obstructive renal disease (ectopic ureteric insertion, obstruction, hydronephrosis). Gastrointestinal tract and cardiac involvement have also been reported. An overlap with Kabuki syndrome is debated.
The association of intellectual deficit, facial dysmorphism (a highly arched palate, pointed chin, and small mouth, hypotelorism, a long nose and large protruding ears), arachnodactyly, hypogenitalism (undescended testes and hypospadias) and failure to thrive. So far, it has been described in three males (including two brothers). An autosomal recessive mode of transmission has been suggested.
A skin disease characterized by formation of bullae without evidence of trauma, hyperpigmentation or hypopigmentation and acrocyanosis in association with microcephaly, subnormal growth and mental development, short tapering fingers, and occasionally deformed nails.
A combination of congenital anomalies consisting of hirsutism, brachycephaly, abnormal position of thumbs, pedes excavatio with claw-toes, facial abnormalities, and mental deficiency.
Hypospadias, retarded mental development, microcephaly, craniofacial dysmorphism, joint laxity, and beaked nails.
Bilateral striatal necrosis (BSN) encompasses a heterogeneous group of neurologic disorders with different causation. Familial infantile striatal degeneration is rare and can be inherited as an autosomal recessive or mitochondrial (see 500003) disorder. The familial form has an insidious onset and a slowly progressive course; the sporadic form is associated with acute systemic illness. Many features of BSN overlap with Leigh syndrome (256000) and certain metabolic disorders, including glutaric acidemia I (231670) and methylmalonic aciduria (251000). See also Aicardi-Goutieres syndrome (225750) (Mito et al., 1986; De Meirleir et al., 1995). Genetic Heterogeneity of Stiatonigral Degeneration Childhood-onset striatonigral degeneration (617054) is caused by mutation in the VAC14 gene (604632) on chromosome 16q22. See also adult-onset autosomal dominant striatal degeneration (ADSD; 609161), caused by mutation in the PDE8B gene (603390) on chromosome 5q13.
A syndrome of unknown etiology with variable expression characterized mainly by non-ossifying fibromata, extraskeletal congenital anomalies such as cafe-au-lait spots, mental retardation, hypogonadism or cryptorchidism, and ocular and cardiovascular malformations.
A rare intellectual disability syndrome with characteristics of severe intellectual disability, spastic paraplegia (with wasting of the lower limbs) and distal transverse defects of the limbs (e.g. ectrodactyly, syndactyly, clinodactyly of the hands and/or feet).
Johnson neuroectodermal syndrome has characteristics of alopecia, anosmia or hyposmia, conductive deafness with malformed ears and microtia and/or atresia of the external auditory canal and hypogonadotropic hypogonadism. So far, less than 30 cases have been described in the literature. Other variable features include a congenital heart defect, facial asymmetry, intellectual deficit, cleft palate, choanal stenosis and an increased tendency for dental caries. The syndrome is transmitted as an autosomal dominant trait. The combination of developmental anomalies present in patients with this syndrome is suggestive of an embryological defect in the formation of the neuroectodermal derivatives of cephalic neural crest.
The term 'X-linked mental retardation-hypotonic facies syndrome' comprises several syndromes previously reported separately. These include Juberg-Marsidi, Carpenter-Waziri, Holmes-Gang, and Smith-Fineman-Myers syndromes as well as 1 family with X-linked mental retardation with spastic paraplegia. All these syndromes were found to be caused by mutation in the XH2 gene and are characterized primarily by severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women (Abidi et al., 2005). Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects. X-linked alpha-thalassemia/mental retardation syndrome (ATR-X; 301040) is an allelic disorder with a similar phenotype with the addition of alpha-thalassemia and Hb H inclusion bodies in erythrocytes.
Kabuki syndrome is a disorder that affects many parts of the body. It is characterized by distinctive facial features including arched eyebrows; long eyelashes; long openings of the eyelids (long palpebral fissures) with the lower lids turned out (everted) at the outside edges; a flat, broadened tip of the nose; and large protruding earlobes. The name of this disorder comes from the resemblance of its characteristic facial appearance to stage makeup used in traditional Japanese Kabuki theater.People with Kabuki syndrome have mild to severe developmental delay and intellectual disability. Affected individuals may also have seizures, an unusually small head size (microcephaly), or weak muscle tone (hypotonia). Some have eye problems such as rapid, involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).Other characteristic features of Kabuki syndrome include short stature and skeletal abnormalities such as abnormal side-to-side curvature of the spine (scoliosis), short fifth (pinky) fingers, or problems with the hip and knee joints. The roof of the mouth may have an abnormal opening (cleft palate) or be high and arched, and dental problems are common in affected individuals. People with Kabuki syndrome may also have fingerprints with unusual features and fleshy pads at the tips of the fingers. These prominent finger pads are called fetal finger pads because they normally occur in human fetuses; in most people they disappear before birth.A wide variety of other health problems occur in some people with Kabuki syndrome. Among the most commonly reported are heart abnormalities, frequent ear infections (otitis media), hearing loss, and early puberty.
An extremely rare syndrome with characteristics of facial dysmorphism, severe intellectual deficiency, cardiac and intestinal anomalies, and growth retardation. Only four cases have been reported in the literature, in three unrelated families. Dysmorphic features include bilateral cleft lip and palate, bulbous nasal tip and eye anomalies. The condition seems to be inherited as an autosomal recessive trait.
A convulsive seizure disorder observed in an isolated tribe in the interior of Tanzania. It is a chronic degenerative disorder of the central nervous system associated with seizures and other neurological complications, characteristic facies, psychomotor retardation, and pachyderma. Kifafa is a Swahili word meaning ""being half-dead and rigid.""
Peters plus syndrome is characterized by anterior chamber eye anomalies, short limbs with broad distal extremities, characteristic facial features, cleft lip/palate, and variable developmental delay/intellectual disability. The most common anterior chamber defect is Peters' anomaly, consisting of central corneal clouding, thinning of the posterior cornea, and iridocorneal adhesions. Cataracts and glaucoma are common. Developmental delay is observed in about 80% of children; intellectual disability can range from mild to severe.
A syndrome of gingival fibromatosis, hepatosplenomegaly, and anomalies of the nose, bones, and nails, occasionally associated with mental retardation.
Lenz microphthalmia syndrome (LMS) is characterized by unilateral or bilateral microphthalmia and/or clinical anophthalmia with malformations of the ears, teeth, fingers, skeleton, and/or genitourinary system. Microphthalmia is often accompanied by microcornea and glaucoma. Coloboma is present in approximately 60% of microphthalmic eyes with severity ranging from isolated iris coloboma to coloboma of the ciliary body, choroid, and optic disk. Ears may be low set, anteverted, posteriorly rotated, simple, cup shaped, or abnormally modeled. Hearing loss has been observed. Dental findings include irregularly shaped, missing, or widely spaced teeth. Duplicated thumbs, syndactyly, clinodactyly, camptodactyly, and microcephaly are common, as are narrow/sloping shoulders, underdeveloped clavicles, kyphoscoliosis, exaggerated lumbar lordosis, long cylindric thorax, and webbed neck. Genitourinary anomalies include hypospadias, cryptorchidism, renal hypoplasia/aplasia, and hydroureter. Approximately 60% of affected males have mild-to-severe intellectual disability or developmental delay.
Spastic paraplegia-23 is an autosomal recessive neurologic disorder characterized by childhood-onset spastic paraplegia resulting in gait difficulties and associated with pigmentary abnormalities, including premature graying of the hair and vitiligo-like or hyperpigmented skin lesions. Some patients may also have a peripheral neuropathy (summary by Lee et al., 2017).
A very rare syndrome with characteristics of microcephaly, craniosynostosis, glaucoma, growth failure and visceral malformations. Only three cases have been reported in the literature in three unrelated families. Dysmorphic features include trigonocephaly, exotropia, cleft palate, beaked nose and low-set ears. All the affected patients have associated congenital visceral malformations including congenital heart defects, diaphragmatic hernia, genital or cerebral abnormalities. The demonstration of congenital glaucoma, hallmark of the syndrome, in the father of an affected patient, supports autosomal dominant inheritance. Prognosis is poor.
Syndrome with the association of epiphyseal dysplasia, short stature, microcephaly and in the first reported cases congenital nystagmus. So far, less than 10 cases have been described in the literature. Variable degrees of intellectual deficit have also been reported. Other occasional features include retinitis pigmentosa and coxa vara. Transmission appears to be autosomal recessive.
Lysine malabsorption with severe malnourishment, extreme flaccidity, and psychomotor retardation.
A very rare syndrome described in two siblings with manifestation of prenatal onset of growth deficiency, microcephaly, hypoplastic genitalia, and birth onset of convulsions.
Arts syndrome, which is part of the spectrum of PRPS1-related disorders, is characterized by profound congenital sensorineural hearing impairment, early-onset hypotonia, delayed motor development, mild to moderate intellectual disability, ataxia, and increased risk of infection, all of which – with the exception of optic atrophy – present before age two years. Signs of peripheral neuropathy develop during early childhood. Twelve of 15 boys from the two Dutch families reported with Arts syndrome died before age six years of complications of infection. Carrier females can show late-onset (age >20 years) hearing impairment and other findings.
Mental retardation, ovarian dysgenesis, congestive cardiomyopathy, broad nasal base, blepharoptosis, and bone abnormalities. The phenotype varies and not all features are present in individual cases. Occasional marfanoid habitus (tall stature with long and thin limbs, little subcutaneous fat, arachnodactyly, joint hyperextensibility, narrow face, small chin, large testes, and hypotonia).
The term '3MC syndrome' encompasses 4 rare autosomal recessive disorders that were previously designated the Carnevale, Mingarelli, Malpuech, and Michels syndromes, respectively. The main features of these syndromes are facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis, and highly arched eyebrows, which are present in 70 to 95% of cases. Cleft lip and palate, postnatal growth deficiency, cognitive impairment, and hearing loss are also consistent findings, occurring in 40 to 68% of cases. Craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies occur in 20 to 30% of cases. Rare features include anterior chamber defects, cardiac anomalies, caudal appendage, umbilical hernia (omphalocele), and diastasis recti (summary by Rooryck et al., 2011). For a discussion of genetic heterogeneity of 3MC syndrome, see 3MC1 (257920).
A constellation of immobile facies, blepharophimosis, micrognathia, microcephaly, midfacial hypoplasia, multiple contractures, hypotonia, arachnodactyly, developmental delay, and other anomalies.
A cerebro-oculomuscular syndrome having the characteristics resembling those of the Marinesco-Sjogren syndrome. Infantile hypotonia, the presenting symptom, is followed in preschool age by ataxia, cataract, and mental retardation. Computed tomography shows cerebellar atrophy, muscle biopsy reveals myopathic changes with vascular degeneration and adipose tissue proliferation, and electron microscopy demonstrates myelin bodies and autophagic vacuoles.
RAB18 deficiency is the molecular deficit underlying both Warburg micro syndrome (characterized by eye, nervous system, and endocrine abnormalities) and Martsolf syndrome (characterized by similar – but milder – findings). To date Warburg micro syndrome comprises >96% of reported individuals with genetically defined RAB18 deficiency. The hallmark ophthalmologic findings are bilateral congenital cataracts, usually accompanied by microphthalmia, microcornea (diameter <10), and small atonic pupils. Poor vision despite early cataract surgery likely results from progressive optic atrophy and cortical visual impairment. Individuals with Warburg micro syndrome have severe to profound intellectual disability (ID); those with Martsolf syndrome have mild to moderate ID. Some individuals with RAB18 deficiency also have epilepsy. In Warburg micro syndrome, a progressive ascending spastic paraplegia typically begins with spastic diplegia and contractures during the first year, followed by upper limb involvement leading to spastic quadriplegia after about age five years, often eventually causing breathing difficulties. In Martsolf syndrome infantile hypotonia is followed primarily by slowly progressive lower limb spasticity. Hypogonadism – when present – manifests in both syndromes, in males as micropenis and/or cryptorchidism and in females as hypoplastic labia minora, clitoral hypoplasia, and small introitus.
Belongs to the group of multiple congenital anomalies/mental retardation syndromes with intellectual deficit, distinctive facies (upward slanting palpebral fissures, squint), kyphoscoliosis, diastasis recti, cryptorchidism, and a congenital heart defect. Autosomal recessive inheritance suggested.
Ataxia, deafness, mental retardation, and upper and lower neuron disease are the principal symptoms.
Moderate to severe intellectual deficit, seizures, short stature, and skeletal dysplasia. Other manifestations can be associated (retinal abnormalities, brachydactyly, prognathism, dental malocclusion). It is transmitted as an autosomal recessive trait.
Mercaptolactate-cysteine disulfiduria with mental retardation, seizures, flat nasal bridge, and highly arched palate.
Ataxia, microcephaly, hypotonia, cataracts, and nystagmus.
A syndrome of mental retardation, short stature, delayed puberty, polydactyly, synmetracarpalia, ocular torticollis, orofacial dysmorphism, and multiple cardiac malformations.
The term '3MC syndrome' encompasses 4 rare autosomal recessive disorders that were previously designated the Carnevale, Mingarelli, Malpuech, and Michels syndromes, respectively. The main features of these syndromes are facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis, and highly arched eyebrows, which are present in 70 to 95% of cases. Cleft lip and palate, postnatal growth deficiency, cognitive impairment, and hearing loss are also consistent findings, occurring in 40 to 68% of cases. Craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies occur in 20 to 30% of cases. Rare features include anterior chamber defects, cardiac anomalies, caudal appendage, umbilical hernia (omphalocele), and diastasis recti (summary by Rooryck et al., 2011). Genetic Heterogeneity of 3MC Syndrome Also see 3MC syndrome-2 (3MC2; 265050), caused by mutation in the COLEC11 gene (612502), and 3MC syndrome-3 (3MC3; 248340), caused by mutation in the COLEC1 gene (607620).
This syndrome has manifestations of microcephaly, deafness, intellectual deficit and facial dysmorphism (facial asymmetry, prominent glabella, low-set and cup-shaped ears, protruding lower lip, micrognathia). It has been described in a mother and her son. The mode of inheritance is probably autosomal dominant.
A craniodigital syndrome marked by characteristic facies, microcephaly, retrognathia, symmetrical digital defects, and retarded mental development.
A very rare disorder, features include microcephaly, facial dysmorphism (beaked nose, low-set ears, downslanting palpebral fissures, micrognathia), mild intellectual deficit, short stature, and cervical spine fusion anomalies producing spinal cord compression.
A rare autosomal dominant syndrome caused by mutations in the MYNC oncogene. It is characterized by microcephaly, limb abnormalities, esophageal and/or duodenal atresia.
Microphthalmia with linear skin defects (MLS) syndrome is characterized by unilateral or bilateral microphthalmia and/or anophthalmia and linear skin defects, usually involving the face and neck, which are present at birth and heal with age, leaving minimal residual scarring. Other findings can include a wide variety of other ocular abnormalities (e.g., corneal anomalies, orbital cysts, cataracts), central nervous system involvement (e.g., structural anomalies, developmental delay, infantile seizures), cardiac concerns (e.g., hypertrophic or oncocytic cardiomyopathy, atrial or ventricular septal defects, arrhythmias), short stature, diaphragmatic hernia, nail dystrophy, hearing impairment, and genitourinary malformations. Inter- and intrafamilial variability is described.
Mental retardation, retinal pigmentary degeneration, spastic cerebral palsy, and microcephaly with variable expressivity. Mirhosseini-Holmes-Walton and Cohen syndromes share many common characteristics.
Males with deafness-dystonia-optic neuronopathy (DDON) syndrome have prelingual or postlingual sensorineural hearing impairment in early childhood, slowly progressive dystonia or ataxia in the teens, slowly progressive decreased visual acuity from optic atrophy beginning approximately age 20 years, and dementia beginning at approximately age 40 years. Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress. The hearing impairment appears to be consistent in age of onset and progression, whereas the neurologic, visual, and neuropsychiatric signs vary in degree of severity and rate of progression. Females may have mild hearing impairment and focal dystonia.
Delayed growth and mental development with ocular disorders.
An inborn error of mucopolysaccharide metabolism with glucosamine-6-sulfate sulfatase deficiency and characteristics similar to those of mucopolysaccharidosis II and IV. Delayed physical and mental development, hypertrichosis, hepatosplenomegaly, dysostosis multiplex, and mild deafness are the main symptoms.
A rare intellectual disability syndrome with characteristics of growth retardation, microcephaly, characteristic facial features (including narrow forehead, bushy eyebrows, hypertelorism, small, downward-slanting palpebral fissures with blepharoptosis, malformed and low-set ears, broad straight nose, thin upper lip and a wide, tented mouth), developmental delay, intellectual disability, speech disorder, and multiple organ malformations (e.g. ventricular septal defect, megaloureter, dilated renal pelvis). Additional manifestations reported include neurocutaneous lesions (including palmoplantar hyperkeratosis), internal hydrocephalus, and bilateral partial soft-tissue syndactyly of second and third toe.
Myhre syndrome is a connective tissue disorder with multisystem involvement, progressive and proliferative fibrosis that may occur spontaneously or following trauma or surgery, mild-to-moderate intellectual disability, and in some instances, autistic-like behaviors. Organ systems primarily involved include: cardiovascular (congenital heart defects, long- and short-segment stenosis of the aorta and peripheral arteries, pericardial effusion, constrictive pericarditis, restrictive cardiomyopathy, and hypertension); respiratory (choanal stenosis, laryngotracheal narrowing, obstructive airway disease, or restrictive pulmonary disease), gastrointestinal (pyloric stenosis, duodenal strictures, severe constipation); and skin (thickened particularly on the hands and extensor surfaces). Additional findings include distinctive craniofacial features and skeletal involvement (intrauterine growth restriction, short stature, limited joint range of motion). To date, 55 individuals with molecularly confirmed Myhre syndrome have been reported.
Syndrome that associates dilated cardiomyopathy with hypergonadotropic hypogonadism. Prevalence is unknown but less than 20 affected families have been described in the literature so far. Occasional findings include a broad nasal base, blepharoptosis, mild intellectual deficit, mild skeletal anomalies and metabolic abnormalities. Mutations in the LMNA gene were recently detected in two sisters with an overlapping clinical phenotype but with additional findings that included a narrow chest, sloping shoulders, aged appearance of the hands and feet and facial dysmorphism (beaked nose and severe retrognathia). Transmission appears to be autosomal recessive.
A rare intellectual disability syndrome with most common characteristics of megalocornea, congenital hypotonia, varying degrees of intellectual disability, psychomotor/developmental delay, seizures, and mild facial dysmorphism (including round face, frontal bossing, antimongoloid slant of the eyes, epicanthal folds, large low set ears, broad nasal base, anteverted nostrils, and long upper lip). Interfamilial and intrafamilial clinical variability has been reported.
A multiple developmental anomalies syndrome with characteristics of neurological abnormalities (including megalencephaly, hypotonia, intellectual disability, abnormal EEG), dysmorphic facial features (high prominent forehead, grooved nasal tip, ptosis, ear anomalies) and acrorenal defects (such as triphalangism, broad halluces, unilateral renal agenesis). Additionally, intrauterine growth restriction, short stature and congenital heart defects may be associated. There have been no further descriptions in the literature since 1997.
Lissencephaly with cerebellar hypoplasia (LCH) affects brain development, resulting in the brain having a smooth appearance (lissencephaly) instead of its normal folds and grooves. In addition, the part of the brain that coordinates movement is unusually small and underdeveloped (cerebellar hypoplasia). Other parts of the brain are also often underdeveloped in LCH, including the hippocampus, which plays a role in learning and memory, and the part of the brain that is connected to the spinal cord (the brainstem).Individuals with LCH have moderate to severe intellectual disability and delayed development. They have few or no communication skills, extremely poor muscle tone (hypotonia), problems with coordination and balance (ataxia), and difficulty sitting or standing without support. Most affected children experience recurrent seizures (epilepsy) that begin within the first months of life. Some affected individuals have nearsightedness (myopia), involuntary eye movements (nystagmus), or puffiness or swelling caused by a buildup of fluids in the body's tissues (lymphedema).
Orbital cysts and other eye defects, multiple cerebral anomalies, and focal dermal defects are the principal characteristics of this syndrome.
A form of ectodermal dysplasia with hyperhidrosis, hyperkeratosis palmaris et plantaris, nail dystrophy, dry and sparse hair, facial erythema, peg-shaped incisors. and malformation of other teeth. Mild mental deficiency was reported in some cases. This condition is considered by some a specific form of a broad category of disorders involving dysplasia of skin appendages and teeth.
A syndrome of delayed development, blepharophimosis, blepharoptosis, dental hypoplasia, deafness, heart defect, cryptorchidism and scrotal hypoplasia in males, and other abnormalities.
The C syndrome, also known as Opitz trigonocephaly syndrome, is a malformation syndrome characterized by trigonocephaly, severe mental retardation, hypotonia, variable cardiac defects, redundant skin, and dysmorphic facial features, including upslanted palpebral fissures, epicanthal folds, depressed nasal bridge, and low-set, posteriorly rotated ears (summary by Kaname et al., 2007). C syndrome shows phenotypic overlap with Bohring-Opitz syndrome, or C-like syndrome (605039), a disorder with more severe features than C syndrome, caused by heterozygous mutation in the ASXL1 gene (612990) on chromosome 20q11.
A polymalformation syndrome that associates multiple skeletal anomalies with microcephaly, facial dysmorphism, urogenital anomalies and intellectual deficit.
W syndrome has characteristics of intellectual deficit, epileptic seizures and facial dysmorphism. Skeletal anomalies are also often present. To date, it has been described in six male patients. The mode of transmission appears to be X-linked dominant.
Perlman syndrome is an autosomal recessive congenital overgrowth syndrome with similarities to Beckwith-Wiedemann syndrome (BWS; 130650). Affected children are large at birth, are hypotonic, and show organomegaly, characteristic facial dysmorphisms (inverted V-shaped upper lip, prominent forehead, deep-set eyes, broad and flat nasal bridge, and low-set ears), renal anomalies (nephromegaly and hydronephrosis), frequent neurodevelopmental delay, and high neonatal mortality. Perlman syndrome is associated with a high risk of Wilms tumor, with a 64% incidence in infants surviving beyond the neonatal period. The tumor is diagnosed at an earlier age in these individuals compared with sporadic cases (less than 2 years and 3-4 years of age, respectively), and there is a high frequency of bilateral tumors (55%). Histologic examination of the kidneys in children with Perlman syndrome shows frequent nephroblastomatosis, which is a precursor lesion for Wilms tumor (summary by Astuti et al., 2012).
A syndrome that is considered as part of the spectrum of Wolf-Hirschhorn Syndrome variability. It maps to the short arm of chromosome 4, at 4p16.
An association of skeletal abnormalities with facial dysmorphism, neonatal respiratory disorders, and feeding problems due to poor suck. Metaphyseal splying, osteopenia, endosteal bone apposition, campomelia, and multiple fractures comprise skeletal abnormalities. The syndrome was originally reported in two siblings, one of whom had a mild developmental delay and other died in infancy. The proposed name ""pointer syndrome"" is based on pointing appearance of the index fingers in both patients and their family.
A rare central nervous system malformation syndrome with characteristics of bilateral porencephaly, absence of the septum pellucidum and cerebellar hypoplasia with absent vermis. Additionally, dysmorphic facial features (hypertelorism, epicanthic folds, high arched palate, prominent metopic suture), macrocephaly, corneal clouding, situs inversus, tetralogy of Fallot, atrial septal defects and/or seizures have been observed.
Primrose syndrome consists of recognizable facial features, macrocephaly, mental retardation, enlarged and calcified external ears, sparse body hair, and distal muscle wasting (summary by Carvalho and Speck-Martins, 2011). Patients with a deletion syndrome involving 3q13.31 (615433) exhibit features overlapping those of Primrose syndrome.
Cerebellar and ocular atrophic disease with delayed or absent psychomotor development, hypotonia, convulsions, hyperreflexia, transient or persistent edema, and dysmorphic facies.
Mild mental deficiency with cataracts, ataxia, deafness, polyneuropthy, and other disorders.
Proud syndrome is an X-linked developmental disorder characterized by agenesis of the corpus callosum, severe mental retardation, seizures, and spasticity. Males are severely affected, whereas females may be unaffected or have a milder phenotype (Proud et al., 1992). Proud syndrome is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome to infantile spasms without brain malformations (EIEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008).
Syndrome with characteristics of intellectual deficit associated with progressive spastic quadriplegia, microcephaly, and glaucoma, absence of the eyebrows and eyelashes, and a malformation of the nose. It has been described in two brothers.
A slowly progressive syndrome of cherubic facies (fullness of the cheeks, producing a typical chubby face suggestive of a cherub) maxillary fibrous dysplasia, gingival enlargement, radiolucent lesions of the jaws, seizures, delayed mental development, stunted growth, and other defects. Insulin dependent diabetes mellitus and vascular skin lesions may occur.
Renpenning syndrome is an X-linked mental retardation syndrome with clinically recognizable features. Affected individuals have microcephaly, short stature, small testes, and dysmorphic facies, including tall narrow face, upslanting palpebral fissures, abnormal nasal configuration, cupped ears, and short philtrum. The nose may appear long or bulbous, with overhanging columella. Less consistent manifestations include ocular colobomas, cardiac malformations, cleft palate, and anal anomalies. Stevenson et al. (2005) proposed that the various X-linked mental retardation syndromes due to PQBP1 mutations be combined under the name of Renpenning syndrome.
An extremely rare neurodegenerative disorder characterised by progressive spinocerebellar ataxia, sensorineural hearing loss, and hypergonadotropic hypogonadism associated with additional neurological manifestations (such as peripheral muscle wasting, nystagmus, intellectual disability or dementia) and ketoaciduria.
A rare multiple congenital anomalies syndrome with characteristics of craniofacial (prominent occiput and forehead, hypertelorism, ocular coloboma, cleft palate), cerebellar (Dandy-Walker malformation, cerebellar vermis hypoplasia) and cardiac (tetralogy of Fallot, atrial and ventricular septal defects) anomalies. To date less than 50 cases have been described. The exact cause is still unknown but mutations in KIAA0196 (8q24.13; coding for strumpellin) have been identified. Sporadic and familial cases have been reported. Transmission is autosomal recessive. Phenotypic variability exists between siblings.
A syndrome of anhidrosis-hypotrichosis, pili torti, microdontia, nail dysplasia, cleft lip/palate, urogenital abnormalities, and mental retardation.
A mild form of gingival hypertrophy with corneal opacity and failure of tooth eruption. Mental retardation and aggressive behavior have been noted but it is not certain whether they are related to this syndrome.
The Richieri-Costa/Guion-Almeida syndrome is characterized by mild mental retardation, short stature, microbrachycephaly, ptosis, esotropia, cleft lip/palate (Richieri-Costa and Guion-Almeida, 1992).
Scott syndrome is a mild platelet-type bleeding disorder characterized by impaired surface exposure of procoagulant phosphatidylserine (PS) on platelets and other blood cells, following activation with Ca(2+)-elevating agents (Munnix et al., 2003).
Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is characterized by pre- and postnatal macrosomia; distinctive craniofacial features (including macrocephaly, coarse facial features, macrostomia, macroglossia, and palatal abnormalities); and commonly, mild to severe intellectual disability with or without structural brain anomalies. Other variable findings include supernumerary nipples, diastasis recti / umbilical hernia, congenital heart defects, diaphragmatic hernia, genitourinary defects, and gastrointestinal anomalies. Skeletal anomalies can include vertebral fusion, scoliosis, rib anomalies, and congenital hip dislocation. Hand anomalies can include large hands and postaxial polydactyly. Affected individuals are at increased risk for embryonal tumors, including Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, hepatocellular carcinoma, and medulloblastoma.
An X-linked mental retardation syndrome characterised by facial dysmorphism (slanted palpebral fissures, narrow face, micrognathia, patulous lower lip, flat or small philtrum, and alternating exotropia and ptosis), short stature, early hypotonia and later hypertonia, prominent upper central incisors, foot deformities (pes planus, metatarsus varus, equinovarus), psychomotor retardation and behavioural problems. Prevalence is unknown. Since its initial description in 1980, the disorder has been described in males from 11 families and in one isolated case. In most cases the syndrome is caused by mutations in the ATRX gene (Xq13.3), however, the causative gene in a large Chinese family has been mapped to a 19.8 Mb interval on Xq25. Transmission is X-linked recessive.
Snyder-Robinson syndrome (SRS) is an X-linked intellectual disability syndrome characterized by asthenic build, facial dysmorphism with a prominent lower lip, kyphoscoliosis, osteoporosis, and speech abnormalities. Developmental delay usually presents as failure to meet early developmental milestones and then evolves to moderate to profound global intellectual disability (which appears to remain stable over time) and variable motor disability. Asthenic habitus and low muscle mass usually develop during the first year, even in males who are ambulatory. During the first decade, males with SRS develop osteoporosis, resulting in fractures in the absence of trauma.
A very rare syndrome described in three siblings of one Japanese family with main features of congenital heart disease, round face with depressed nasal bridge, small mouth, short stature, and relatively dark skin and typical dermatoglyphic anomalies, and intellectual deficit.
Syndrome that is marked by characteristic facies associated with dysarthria, delayed psychomotor development, ataxia, scoliosis and foot deformities. Three cases have been described and transmission appears to be autosomal recessive.
Dwarfism, coarse facial features, sclerotic changes of the skull, contractures of the hips and knees, hyperextensibility of stubby and tapering fingers, kyphosis, scoliosis, pectus carinatum, ossification of the metaphyses of the long bones, flat vertebral crests, and delayed growth and mental development.
Spondyloperipheral dysplasia is a disorder that impairs bone growth. This condition is characterized by flattened bones of the spine (platyspondyly) and unusually short fingers and toes (brachydactyly), with the exception of the first (big) toes. Other skeletal abnormalities associated with spondyloperipheral dysplasia include short stature, shortened long bones of the arms and legs, exaggerated curvature of the lower back (lordosis), and an inward- and upward-turning foot (clubfoot). Additionally, some affected individuals have nearsightedness (myopia), hearing loss, and intellectual disability.
Stuve-Wiedemann syndrome is an autosomal recessive disorder characterized by bowing of the long bones and other skeletal anomalies, episodic hyperthermia, and respiratory and feeding distress usually resulting in early death (Dagoneau et al., 2004). See also 'classic' Schwartz-Jampel syndrome type 1 (SJS1; 255800), a phenotypically similar but genetically distinct disorder caused by mutation in the HSPG2 gene (142461) on chromosome 1p36.
A rare genetic disease with characteristics of hypertelorism with facial features that can closely resemble craniofrontonasal dysplasia, such as prominent forehead, widow's peak, heavy and broad eyebrows, long palpebral fissures, ptosis, high and broad nasal bridge, short nose, low-set ears, natal teeth, thin upper lip and a grooved chin. Limb features include fifth-finger clinodactyly, pes adductus, mild interdigital webbing. Urogenital features include bilateral cryptorchidism and shawl scrotum in males. Other manifestations include umbilical hernia/omphalocele and cardiac defects. Psychomotor development is normal.
A rare variant of frontonasal dysplasia characterised by distinct craniofacial (large fontanelle, hypertelorism, bifid nasal tip, nasal clefting, brachycephaly, median cleft face, carp-shaped mouth), brain (interhemispheric lipoma, agenesis of the corpus callosum), and limb (tibial hypoplasia/aplasia, club foot, symmetric preaxial polydactyly of the feet and bilateral clubbed and thickened nail malformations as well as intellectual disability.
Toriello-Carey syndrome is a multiple congenital anomaly disorder with variable systemic manifestations, most commonly including mental retardation, agenesis of the corpus callosum, postnatal growth delay, cardiac defects, usually septal defects, distal limb defects, and urogenital anomalies in affected males. Patients have facial dysmorphic features, micrognathia, including full cheeks, hypertelorism, flattened nasal bridge, anteverted nares, and short neck. Not all features are found in all patients and some patients may have additional features such as anal anomalies or hernias (summary by Toriello et al., 2003). In a review of the Toriello-Carey syndrome, Toriello et al. (2016) stated that while corpus callosum abnormalities and micrognathia with highly arched or cleft palate are seen in most patients, other manifestations are widely variable. They noted that etiologic heterogeneity has been observed in reported patients, with at least 20% of patients having chromosome anomalies, and that no good candidate genes have been identified by exome sequencing. The authors commented that this condition might not be a unitary diagnostic entity. They recommended chromosome microarray for any child suspected of having the condition, followed by standard of care by genetic testing.
This syndrome has characteristics of intellectual deficit, short stature, obesity, genital abnormalities, and hand and/or toe contractures. It has been described in two brothers and in one isolated case. This syndrome is similar to Prader-Willi syndrome, but the hand contractures and osteoporosis, together with the lack of hypotonia, indicate this is a different entity.
Syndrome that is characterised by intellectual deficit, choroideraemia, acrokeratosis verruciformis, anhidrosis, and skeletal deformities. It has been observed in a single kindred. The syndrome is transmitted as an X-linked recessive trait and may be caused by a small X-chromosome deletion.
Waisman syndrome is an X-linked neurologic disorder characterized by delayed psychomotor development, intellectual disability, and early-onset Parkinson disease (summary by Wilson et al., 2014).
A rare otorhinolaryngological malformation syndrome with characteristics of a distinctive mask-like facial dysmorphism, lacrimal duct obstruction, extrapyramidal features, digital malformations and intellectual disability. Reported in 3 families to date. The facies has a mask-like appearance due to weakness of facial muscles and lacrimal duct obstruction is characteristic. Clinical features also include telecanthus, bulky nose, broad nasal bridge, sometimes a hypoplastic midface, longitudinal cheek furrows, trapezoidal upper lip and malformation of the ears. Intellectual disability, cutaneous syndactyly, torsion dystonia, increased deep tendon reflexes; Babinski sign, poor coordination and joint laxity are also observed.
A multiple congenital anomalies syndrome with characteristics of moderate-to-severe intellectual disability, decreased muscle mass, microcephaly, facial dysmorphism (prominent ears, midfacial hypoplasia, small mouth and cleft palate), clinodactyly of the fingers, delayed osseous maturation and general bone hypoplasia. The syndrome has been described in a brother and sister and an autosomal recessive mode of inheritance has been suggested. There have been no further descriptions in the literature since 1977.
Wieacker-Wolff syndrome is a severe X-linked recessive neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero (fetal akinesia). Affected boys are born with severe contractures, known as arthrogryposis, and have delayed motor development, facial and bulbar weakness, characteristic dysmorphic facial features, and skeletal abnormalities, such as hip dislocation, scoliosis, and pes equinovarus. Those that survive infancy show mental retardation. Carrier females may have mild features of the disorder (summary by Hirata et al., 2013).
Mental retardation with multiple congenital abnormalities consisting of craniofacial anomalies, delayed development, skeletal anomalies, urogenital anomalies, and deformed hands.
A craniodigital syndrome of prenatal growth retardation, microcephaly, mental retardation, syndactyly of the fingers, and minor facial anomalies.
A form of cerebral palsy with characteristics of congenital pseudobulbar (suprabulbar) paresis manifesting as selective weakness of the lips, tongue and soft palate, dysphagia, dysphonia, drooling and jaw jerking. Mean age at diagnosis is 6 years. The main clinical features are spasticity and limited movements around the mouth and throat from an early age, and brisk jaw jerks. Most cases are sporadic but several families with more than one affected member have been reported. Inheritance in these families appeared to follow an autosomal dominant pattern with variable expression and penetrance.
SCAX1 is an X-linked recessive neurologic disorder characterized by hypotonia at birth, delayed motor development, gait ataxia, difficulty standing, dysarthria, and slow eye movements. Brain MRI shows cerebellar ataxia (summary by Bertini et al., 2000). Genetic Heterogeneity of X-linked Spinocerebellar Ataxia X-linked recessive spinocerebellar ataxia (SCAX) is a clinically and genetically heterogeneous disorder. See also SCAX2 (302600), SCAX3 (301790), SCAX4 (301840), and SCAX5 (300703).
Atkin-Flaitz syndrome has characteristics of moderate to severe intellectual deficit, short stature, macrocephaly, and characteristic facies. It has been described in 11 males and three females from three successive generations of the same family. The males also presented with postpubertal macroorchidism. Transmission is X-linked.
Nonsyndromic mental retardation with a large head, relatively short stature, highly arched palate, square facies, short hands and feet, and macroorchidism.
Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range: In utero with fetal presentation of nonimmune hydrops, cardiomyopathy, and intrauterine growth restriction. Newborns, who can have microcephaly, poor feeding, and encephalopathy. Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS). Toddlers, who can have poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures. Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, thromboembolic compications, and/or subacute combined degeneration of the spinal cord.
Nonsyndromic mental retardation with hypotelorism, strabismus, large ears, and low birthweight.
Nonsyndromic mental retardation with inconsistent abnormalities.
Nonsyndromic mental retardation. Hypotonia in infancy, poor or absent speech, and other disorders are occasionally associated.
Nonsyndromic mental retardation. Variable minor clinical features include hypotonia, microcephaly, hypoactivity, feeding difficulty, intrauterine growth retardation, visual impairment, and seizures.
X-linked mental retardation-19 (MRX19) is a nonsyndromic form of mild to moderate mental retardation. Carrier females may be mildly affected. Mutation in the RPS6KA3 gene also causes Coffin-Lowry syndrome (CLS; 303600), a mental retardation syndrome with dysmorphic facial features and skeletal anomalies. Some patients with RPS6KA3 mutations have an intermediate phenotype with mental retardation and only mild anomalies reminiscent of CLS. These individuals have mutations resulting in some residual protein function, which likely explains the milder phenotype (summary by Field et al., 2006).
Impaired mental functioning occurs as an isolated feature or as part of many syndromes listed in the X-linked catalog. Mental retardation that is not associated with other distinguishing features is referred to as 'nonspecific.' The Human Gene Mapping Nomenclature Committee (Mulley et al., 1992) proposed to designate each newly reported apparently unique X-linked mental retardation (MRX) family with gene symbols (e.g., MRX1, MRX2) if a minimal lod score of 2.0 was demonstrated between the MR locus and 1 or more X chromosome markers.
Nonsyndromic mental retardation with speech disorders.
Bohring-Opitz syndrome (BOS) is characterized by distinctive facial features and posture, growth failure, variable but usually severe intellectual disability, and variable anomalies. The facial features may include microcephaly or trigonocephaly / prominent (but not fused) metopic ridge, hypotonic facies with full cheeks, synophrys, glabellar and eyelid nevus flammeus (simplex), prominent globes, widely set eyes, palate anomalies, and micrognathia. The BOS posture, which is most striking in early childhood and often becomes less apparent with age, is characterized by flexion at the elbows with ulnar deviation and flexion of the wrists and metacarpophalangeal joints. Feeding difficulties in early childhood, including cyclic vomiting, have a significant impact on overall health; feeding tends to improve with age. Seizures are common and typically responsive to standard epileptic medications. Minor cardiac anomalies and transient bradycardia and apnea may be present. Affected individuals may experience recurrent infections, which also tend to improve with age. Isolated case reports suggest that individuals with BOS are at greater risk for Wilms tumor than the general population, but large-scale epidemiologic studies have not been conducted.
Nonsyndromic mental retardation with microcephaly, restlessness, and hyperactivity.
Nonsyndromic mental retardation with delayed speech development and occasional strabismus and single palmar creases.
Nonsyndromic mental retardation associated with relative macrocephaly, broad and high forehead, round face, flat nasal bridge, obesity, and hyperactivity.
ARX-related mental retardation is a form of nonsyndromic X-linked mental retardation. It is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1; 308350) to Partington syndrome (309510) (Kato et al., 2004; Wallerstein et al., 2008).
Nonsyndromic moderate to severe mental retardation without any clinical manifestations.
Partington syndrome is an X-linked developmental disorder characterized by mental retardation and variable movement disturbances. Partington syndrome is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1; 308350) to nonsyndromic mental retardation (300419). Although males with ARX mutations are often more severely affected, female mutation carriers may also be affected (Kato et al., 2004; Wallerstein et al., 2008).
Pettigrew syndrome is characterized by mental retardation and highly variable additional features, including choreoathetosis, hydrocephalus, Dandy-Walker malformation, seizures, and iron or calcium deposition in the brain, both between and within families (summary by Cacciagli et al., 2014). See 311510 for another X-linked mental retardation syndrome associated with basal ganglia disease (Waisman syndrome). See 220219 for another mental retardation syndrome with Dandy-Walker malformation.
A very rare X-linked multisystem genetic disease characterised by intellectual disability, truncal obesity, gynaecomastia, hypogonadism, dysmorphic facial features, and short stature. The syndrome has been described in two families to date. The syndrome has been linked to a mutation in the consensus donor splice site of the histone deacetylase 8 HDAC8 gene (Xq13). X-linked recessive transmission and X-linked dominant inheritance with absence of male-to-male transmission have been reported.
A rare X-linked intellectual disability syndrome with characteristics of intellectual disability associated with short stature, obesity, primary hypogonadism and an ichthyosiform skin condition. There have been no further descriptions in the literature since 1982.
The principal features of Sabinas brittle hair syndrome, a form of nonphotosensitive trichothiodystrophy (TTDN; see 234050), include congenital hypotrichosis, mild to moderate onychodysplasia, varying mental retardation, and sterility. Ocular dysplasias are sometimes present and dentition is normal (Howell et al., 1980).
A rare X-linked intellectual disability syndrome with characteristics of failure to thrive, speech delay, intellectual disability, muscle hypotonia, spastic diplegia, optic atrophy with myopia and distinct facial features (including triangular face, bifrontal narrowness, deeply set eyes, low-set/cupped ears, prominent nose, short philtrum, and thin upper lip with tented morphology) that can be evident from birth. Additional manifestations reported in some patients include large joint contractures and pectus excavatum (which become more evident with age) and seizures.
Riboflavin transporter deficiency neuronopathy is a disorder that affects nerve cells (neurons). Affected individuals typically have hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and signs of damage to other nerves.In addition to nerves in the inner ear, riboflavin transporter deficiency neuronopathy involves nerves found in the part of the brain that is connected to the spinal cord (the brainstem), specifically in a region of the brainstem known as the pontobulbar region. Damage to these nerves causes paralysis of the muscles controlled by them, a condition called pontobulbar palsy. Nerves in the pontobulbar region help control several voluntary muscle activities, including breathing, speaking, and moving the limbs. As a result of pontobulbar palsy, people with riboflavin transporter deficiency neuronopathy can have breathing problems; slurred speech; and muscle weakness in the face, neck, shoulders, and limbs. Affected individuals can also have muscle stiffness (spasticity) and exaggerated reflexes.The age at which riboflavin transporter deficiency neuronopathy begins varies from infancy to young adulthood. When the condition begins in infancy, the first symptom is often breathing problems caused by nerve damage, which can be life-threatening. When the condition begins in children or young adults, sensorineural hearing loss usually occurs first, followed by signs of pontobulbar palsy.If not treated, the signs and symptoms of riboflavin transporter deficiency neuronopathy worsen over time. Severe breathing problems and respiratory infections are the usual cause of death in people with this condition. Without treatment, affected infants typically survive less than one year. However, those who develop the condition after age 4 often survive more than 10 years.Riboflavin transporter deficiency neuronopathy encompasses two conditions that were once considered distinct disorders: Brown-Vialetto-Van Laere syndrome (BVVLS) and Fazio-Londe disease. The two conditions have similar signs and symptoms, but Fazio-Londe disease does not include sensorineural hearing loss. Because these two conditions share a genetic cause and have overlapping features, researchers determined that they are forms of a single disorder.
Brunner syndrome is a recessive X-linked disorder characterized by impulsive aggressiveness and mild mental retardation associated with MAOA deficiency (Brunner et al., 1993).
A syndrome of craniosynostosis, limb abnormalities, brevicollis, micrognathia, pulmonary stenosis, and genital defects.
A multiple congenital anomalies/dysmorphic syndrome with characteristics of a progressively coarse acromegaloid-like facial appearance, thickening of the lips and intraoral mucosa, large and doughy hands and, in some cases, developmental delay. The syndrome appears to be part of a phenotypic spectrum that includes hypertrichotic osteochondrodysplasia, Cantu type and hypertrichosis-acromegaloid facial appearance syndrome.
This syndrome is characterised by congenital cataract, generalised hypertrichosis and intellectual deficit. It has been described in two Egyptian siblings born to consanguineous parents. It is transmitted as an autosomal recessive trait.
Malformations of the kidneys (renal aplasia or dysplasia) and limbs (mainly split hand and foot and digital abnormalities) with variable defects of other organs, short stature, and intellectual impairment.
A vaccine comprise of a canarypox viral vector that carries the gene for human B7.1 (CD80 antigen) with potential use as an autologous therapeutic cancer vaccine. Tumor cells harvested from a patient are infected with ALVAC-hB7 1, thereby producing an autologous cell line that exhibits increased expression of HLA class I and class II, CD54 (ICAM), and CD80. Increased expression of these proteins by this autologous cell line may activate an antitumor T-cell response when the modified cells are administered to the patient. (NCI04)
The isethionate salt of mivobulin, a synthetic colchicine analogue with potential antineoplastic activity. Mivobulin isethionate binds to tubulin, thereby inhibiting microtubule polymerization and mitosis.
A benzonitrile derivative capable of inhibiting some prenyltransferases. L-778,123 is a dual inhibitor of farnesyl:protein and geranylgeranyl:protein transferases; both enzymes catalyze prenylation of oncoprotein KRAS, a prerequisite step in activation of KRAS in signal transduction pathway of apoptosis. Although this agent was developed in part as an anti-KRAS agent, L-778,123 failed in a Phase I trial to inhibit KRAS, which is associated with many types of solid tumors.
A radioimmunoconjugate consisting of 81C6, a murine IgG2 anti-tenascin monoclonal antibody labeled with iodine 131 (I-131), with radioimaging and radioimmunotherapeutic activities. Using monoclonal antibody 81C6 as a carrier for I-131 results in the targeted imaging and/or destruction of cells expressing tenascin. Tenascin is an extracellular matrix protein which is overexpressed in gliomas and other cancers.
A radioimmunoconjugate of a IgG2 monoclonal antibody (MoAb) 81C6 labeled with iodine 123 (I-123). MoAb 81C6 recognizes the extracellular matrix antigen tenascin (hexabrachion), which is up-regulated in gliomas and other cancers. Using MoAb 81C6 as a carrier for I-123 allows detection of tumor localization and distribution of MoAb 81C6 in diagnostic imaging procedures.
A radioimmunoconjugate of a human-murine chimeric IgG2 monoclonal antibody (MoAb) 81C6 labeled with an alpha-emitting radionuclide Astatine 211 (At-211), with imaging and radioimmunotherapeutic properties. MoAb 81C6 recognizes the extracellular matrix antigen tenascin (hexabrachion), which is up-regulated in gliomas and other cancers. Using MoAb 81C6 as a carrier for At-211 results in the targeted imaging and/or destruction of cells expressing tenascin.
A cancer vaccine composed of peptides derived from a tumor-associated protein encoded by a mutated Von Hippel-Lindau (VHL) oncogene. VHL peptide vaccine may stimulate a cytotoxic T cell response against tumor cells expressing the VHL tumor-associated protein. (NCI04)
An adenovirus vector engineered to produce CD40 ligand. For use as a possible gene therapy agent. May induce apoptosis through the TNF pathway.
A monoclonal antibody directed against human Vascular Endothelial Growth Factor (VEGF), a protein that stimulates angiogenesis, and prevents VEGF from binding to its receptors, causing inhibition of angiogenesis. (NCI)
A radioactive isotope of iodine, a nonmetallic element of the halogen group. With a half-life of 60 days, iodine 125 occurs naturally and can be produced artificially. This agent has both therapeutic and diagnostic uses, particularly in thyroid disease. (NCI04)
A peptide vaccine containing the prostate specific antigen (PSA) with potential antineoplastic activity. PSA, a glycoprotein secreted by prostatic epithelial and ductal cells, is overexpressed in prostate cancer cells and is used as a tumor marker for both diagnosis and treatment evaluation. Vaccination with PSA peptide vaccine may produce anti-PSA antibodies as well as elicit a cytotoxic T-cell (CTL) response against prostate cancer cells expressing this antigen, thereby decreasing tumor cell growth.
A glioma that affects the optic tract. This condition can be seen in association with neurofibromatosis 1. It is most commonly seen in the pediatric age group.
A chimeric protein consisting of the Fv portion of a monoclonal antibody attached to a fragment of Pseudomonas exotoxin A without its cell-binding region. LMB-1 immunotoxin targets B3, a Lewis Y-related carbohydrate epitope found on some solid tumors. The antibody attaches to the tumor cell and the exotoxin stops protein synthesis by inactivating elongation factor 2. (NCI04)
A mouse-derived anti-human CD19 monoclonal antibody linked to pokeweed (Phytolacca americana) antiviral protein (PAP) with antileukemic activity. The monoclonal antibody portion specifically binds to the CD19 antigen, a cell surface molecule normally expressed only by B lymphocytes and follicular dendritic cells, while over-expressed in B-lineage lymphocytic leukemia cells. Following internalization, PAP, a plant hemitoxin and a ribosome-inactivating protein, is cleaved from the immunoconjugate and released into the cytoplasm where it enzymatically removes a single adenine base from a conserved, surface exposed loop sequence of rRNA leading to inhibition of protein synthesis and cell growth, but not necessarily cell death.
A synthetic formulation in which the antineoplastic agent cisplatin is encapsulated in lipids. Cisplatin liposomal consists of small aggregates of cisplatin covered by a single lipid bilayer. Encasement in liposomes improves cisplatin's tumor bioavailability and toxicity profile. Liposomal encapsulation does not affect the pharmacological properties of cisplatin directly. Cisplatin forms highly reactive, charged, platinum complexes which bind to nucleophilic groups such as GC-rich sites in DNA, inducing intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links. These cross-links result in apoptosis and cell growth inhibition. (NCI04)
CancerVax is an allogenic polyvalent vaccine composed of irradiated but viable cells from three melanoma cell lines and Bacille Calmette-Guerin (BCG). The vaccine was shown to induce humoral and cellular immune responses against multiple tumor antigens present on melanoma cells. A significant correlation between the magnitude of immune responses to the vaccine and the overall survival of patients receiving adjuvant therapy with CancerVax after surgical resection of stage III and IV melanoma was reported. Vaccine testing in patients with advanced colon cancer merits further investigation. (NCI)
A myelodysplastic syndrome characterized by bi-cytopenia or pancytopenia and dysplastic changes in 10% or more of the cells in two or more of the myeloid cell lines. (WHO, 2001)
A water-soluble prodrug derived from the African bush willow (Combretum caffrum) with tumor vascular-targeting activity. In vivo, combretastatin A4 phosphate is dephosphorylated to its active metabolite, combretastatin A4, which binds to tubulin and inhibits microtubule depolymerization, resulting in morphological changes in proliferating endothelial cells. As a result, the permeability of tumor vasculature is increased, leading to reduced tumor blood flow and ischemic necrosis of tumor tissue. In vitro, combretastatin A4 phosphate has been shown to be directly cytotoxic to proliferating endothelial cells and tumor cells. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43316&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43316&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2503"" NCI Thesaurus)
A recombinant immunotoxin consisting of the Fv portion of the anti-CD22 antibody RFB4 fused to a fragment of Pseudomonas exotoxin-A with potential antineoplastic activity. BL22 immunotoxin binds to CD22, an antigen expressed in B-cell malignancies, thereby delivering its toxin directly to tumor cells. The toxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also blocks translational elongation via binding to elongation factor-2 in eukaryotic cells.
A 7-methylthiomethyl ether derivative of paclitaxel with antineoplastic activity. BMS-184476 binds to and stabilizes the resulting microtubules, thereby inhibiting microtubule disassembly which results in cell- cycle arrest at the G2/M phase and apoptosis. (NCI)
A murine monoclonal antibody with potential antineoplastic activity. Monoclonal antibody HeFi-1 binds to CD30, a cell surface antigen found on mitogen-activated B-cells and T-cells, and Reed-Sternberg cells. Monoclonal antibody HeFi-1 has been shown to arrest tumor growth and prevent metastasis in animal models. (NCI04)
A radioimmunoconjugate of folic acid labeled with indium 111 (In-111) with immunotherapeutic property. In 111 Folic Acid emits gamma radiation and X-Ray photons that can be captured by gamma camera allowing imaging of tumor cells that express folate receptors.
A vaccinia virus based vaccine expressing human tumor associated epithelial mucin (DF3 antigen; MUC1). MUC1 antigen, a membrane bound glycoprotein expressed by most glandular and ductal epithelial cells, is overexpressed in various tumors such as breast, prostate, and ovarian cancers. This vaccine could be used in development of immunotherapeutics against cancers expressing MUC1.
A targeted radioimmunoconjugate composed of a murine monoclonal anti-CD20 antibody (ibritumomab) linked by a chelator (tiuxetan) to the imaging radioisotope indium-111. This radioimmunoconjugate binds to CD20-positive cells, permitting radioimmuno-localization of CD20-positive cell biodistribution.
A cancer vaccine composed of naked plasmid DNA of the gene for the tumor-associated antigen alpha-fetoprotein (AFP), a macromolecule that acts as a specific immunologic target for hepatocellular carcinoma. This agent exerts an antitumor effect by inducing cytotoxic T-lymphocytes to attack AFP-expressing tumor cells. (NCI04)
A protein produced by influenza viruses that can link the core material in the virus to the viral envelope. These proteins are involved in both the release of the viral genome into infected cells and the subsequent repackaging of the replicated genome into new virions.
A murine monoclonal antibody (MoAb) against human fibroblast activation protein (FAP). FAP is a 95 kDa cell surface glycoprotein and an inducible tumor stromal antigen of epithelial cancers and of a subset of soft tissue sarcomas. FAP shows a very limited distribution pattern in normal tissues, thereby MoAb F19 has possible diagnostic and therapeutic applications in epithelial cancers.
A radioimmunoconjugate of a murine monoclonal antibody (MoAb) F19 labelled with Iodine 131 (I-131). MoAb F19 was raised against fibroblast activation protein (FAP), which is highly expressed by tumor stromal cells. Using MoAb F19 as a carrier for I-131 results in the targeted imaging and/or destruction of cells overexpressed FAP.
A childhood rhabdomyosarcoma for which a patient has received treatment in the past.
A covalent conjugate of recombinant interferon alpha, subtype 2b, and polyethylene glycol (PEG), used as an antiviral and antineoplastic agent. The biological activity of this agent is derived from its interferon alpha-2b protein moiety. Interferons alfa bind to specific cell-surface receptors, leading to the transcription and translation of genes whose protein products mediate antiviral, antiproliferative, anticancer, and immune-modulating effects. The PEG moiety lowers the clearance of interferon alpha-2b, thereby extending the duration of its therapeutic effects, but may also reduce the interferon-mediated stimulation of an immune response. (NCI04)
A small round cell tumor with or without neural differentiation which is confined to a specific site without evidence of spread to another anatomic site.
The reemergence of Askin tumor after a period of remission.
A cancer vaccine prepared from human melanoma cancer cells. It can be used alone or with other therapy in treating melanoma.
A malignant neoplasm which is confined to a specific anatomic site and has not spread to other sites.
A peptide vaccine containing an epitope of human tumor-associated KSA antigen (Ep-CAM) conjugated with keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. KSA antigen, a type-I transmembrane glycoprotein and a cellular adhesion molecule with a molecular mass of 40 kDa, is overexpressed on the majority of epithelial tumor cells. KSA antigen is conjugated with KLH, an immunostimulant and a hapten carrier, to enhance immune recognition. Vaccination with KSA-KLH may result in the production of antibodies as well as eliciting a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the KSA antigen.
A recombinant virus-based vaccine that contains various peptide antigens. Fowlpox virus is an attractive vector because its genome is easy to manipulate and it does not multiply in human tissues. Strong CD8 T cell responses may be induced after prolonged immunization and have been associated with tumor regression.
An anticancer drug formed by the combination of diphtheria toxin and a colony-stimulating factor (GM-CSF). The colony-stimulating factor is attracted to cancer cells, and the diphtheria toxin kills the cells.
A recently diagnosed ependymoma during childhood.
The reemergence of ependymoma in childhood after a period of remission.
A mouse anti-human CD19 monoclonal antibody (MoAb). CD19 as well as CD22 are cell surface antigens present on a majority of B lymphocytes, including early B progenitor cells. Anti-CD19 MoAb, either alone or in combination with other immunotherapeutic agents, may be used in management of B-cell malignancies.
An Fc-engineered monoclonal antibody directed against human CD20 with potential antineoplastic activity. Ocaratuzumab specifically binds to CD20 antigen (B1), preventing mitogen-induced B-cell proliferation; inhibiting B-cell differentiation; and promoting antibody-dependent cell-mediated cytotoxicity (ADCC) and apoptosis of B cells expressing CD20. The Fc portion of this monoclonal antibody has been engineered to possess a higher binding affinity for variant Fc receptors on T helper cells, resulting in an augmentation of the anti-tumor immune response. Because of Fc engineering, this agent may be significantly more potent than rituximab in inducing B cell-directed ADCC. CD20 is a non-glycosylated cell surface phosphoprotein that is exclusively expressed on B cells during most stages of B cell development.
A whole cell vaccine expressing human granulocyte macrophage-colony stimulating factor (GM-CSF) with potential antineoplastic activity. Tumor cells from prostate cancer patients are harvested and then genetically modified to secrete GM-CSF, an immune stimulatory growth factor that plays a key role in stimulating the body's immune responses against tumor cells. Because the vaccine is derived from allogenic cells, it has demonstrated a favorable side effect profile than other approaches of delivering long-lasting GM-CSF.
A semisynthetic derivative of the vinca alkaloid vinblastine, with potential antineoplastic activity. Like vinblastine, anhydrovinblastine targets and binds to tubulin and inhibits microtubule formation, resulting in disruption of mitotic spindle assembly and causing tumor cell cycle arrest in the M phase.
Stage IB includes: (T2a, N0, M0, G1, GX); (T2b, N0, M0, G1, GX). T2a: Superficial tumor more than 5 cm in greatest dimension. T2b: Deep tumor more than 5 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Grade 1. GX: Grade cannot be assessed. (AJCC 7th ed.)
Stage IIA includes: (T1a, N0, M0, G2, G3); (T1b, N0, M0, G2, G3). T1a: Superficial tumor 5 cm or less in greatest dimension. T1b: Deep tumor 5 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G2: Grade 2. G3: Grade 3. (AJCC 7th ed.)
Stage IIB includes: (T2a, N0, M0, G2); (T2b, N0, M0, G2). T2a: Superficial tumor more than 5 cm in greatest dimension. T2b: Deep tumor more than 5 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G2: Grade 2. (AJCC 7th ed.)
Stage IA includes: (T1a, N0, M0, G1, GX); (T1b, N0, M0, G1, GX). T1a: Superficial tumor 5 cm or less in greatest dimension. T1b: Deep tumor 5 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Grade 1. GX: Grade cannot be assessed. (AJCC 7th ed.)
Stage III includes: (T2a, T2b, N0, M0, G3); (Any T, N1, M0, Any G). T2a: Superficial tumor more than 5 cm in greatest dimension. T2b: Deep tumor more than 5 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. G3: Grade 3. There is no T2a for the pathologic group. (AJCC 7th ed.)
Stage IV includes: Any T, Any N, M1, Any G. M1: Distant metastasis. (AJCC 7th ed.)
A radioimmunoconjugate consisting of BC8, a murine IgG1 anti-CD45 monoclonal antibody labeled with iodine 131 (I-131), with radioimmunotherapeutic properties. Using monoclonal antibody BC8 as a carrier for I-131 results in the targeted destruction of cells expressing CD45. CD45 is tyrosine phosphatase expressed on virtually all leukocytes, including myeloid and lymphoid precursors in bone marrow and mature lymphocytes in lymph nodes; it is also expressed on most myeloid and lymphoid leukemic cells, but not on mature erythrocytes or platelets. (NCI04)
A vaccine containing a clustered pancarcinoma carbohydrate antigen, Thomsen-Friedenreich (TF) antigen, conjugated with keyhole limpet hemocyanin (KLH) with potential antineoplastic activity. TF antigen is a disaccharide epitope (galactose-beta1-3-N-acetylgalactose), normally O-linked to serine or threonine of tumor-associated epithelial mucins. This vaccine contains the TF epitope cluster (c) that is synthesized by linking 3 copies of the TF epitope on a threonine backbone to achieve the essential immunogenic structure. KLH is a hapten carrier and serves as an immunostimulant to improve immune recognition. Vaccination with TF(c)-KLH peptide vaccine may produce antibodies and elicit a cytotoxic T lymphocyte (CTL) response against those tumor cells expressing TF antigen, resulting in decreased tumor growth.
A liposome-encapsulated formulation of lurtotecan with antineoplastic activity. Lurtotecan, a semisynthetic analogue of camptothecin, selectively stabilizes the topoisomerase I-DNA covalent complex and forms an enzyme-drug-DNA ternary complex during S phase of the cell cycle, thereby inhibiting religation of topoisomerase I-mediated single-stranded DNA breaks. This ultimately results in an inhibition of DNA replication, inducing double-stranded DNA breakages, obstruction of RNA and protein synthesis and triggering apoptosis. Furthermore, this agent also stimulates degradation of topoisomerase I, likely mediated through ubiquitin-proteasomal pathway. Liposomal delivery of lurtotecan improves its penetration and delivery into tumors while lowering systemic side effects.
A second-generation, mixed-backbone, phosphorothioate antisense oligonucleotide (ODN) with potential antitumor activity. MG 98 is a highly specific inhibitor of translation of the mRNA for human DNA (cytosine-5-)-methyltransferase 1 (DNMT1), hybridizing to the 3' un-translated region of DNMT1 mRNA. The silencing of DNMT1 translation by MG 98 may result in the prevention or reversal of abnormal methylation of tumor suppressor genes and ultimately in tumor growth inhibition or tumor regression.
A vaccine consisting of recombinant vaccinia virus, based on the modified vaccinia virus Ankara (MVA) that encodes the melanoma-associated antigen tyrosinase. Vaccination with vaccinia-tyrosinase may stimulate the host immune system to mount a cytotoxic T-cell response against tumor cells expressing tyrosinase. Tyrosinase is a melanoma-specific differentiation agent that catalyzes the synthesis of the melanin precursor L-3,4-dihydroxyphenylalanine (L-DOPA).
A childhood benign or malignant germ cell tumor arising from an anatomic site other than the brain.
A germ cell tumor that arises from the testis during childhood.
A germ cell tumor that arises from the ovary and occurs in children.
A malignant germ cell tumor in children arising from an anatomic site other than the testis or ovary.
A radioimmunoconjugate of m170 monoclonal antibody (MoAb) conjugated with isotope yttrium 90. MoAb m170 is a murine MoAb that recognizes MUC-1 antigen present on the surface of many adenocarcinomas. This radioimmunoconjugate emits beta particles that cause cytotoxicity in tumor cells and has both imaging and therapeutic uses.
A radioimmunoconjugate of the monoclonal antibody (MoAb) M170 labelled with Indium 111 (In-111). MoAb M170 recognizes an epitope of MUC1 mucins, which are up-regulated in many human adenocarcinomas. In-111 MoAb M170 emits gamma radiation and X-Ray photons, thereby allowing detection of tumor localization and distribution of MoAb M170 in diagnostic imaging procedures.
A radioimmunoconjugate of a murine monoclonal antibody, MoAb Lym-1, labeled with yttrium 90 (Y-90). MoAb Lym-1 recognizes an epitope of the histocompatibility antigen HLA-DR, which is over-expressed on most B-cell lymphomas. Y-90 MoAb Lym-1 delivers Y-90 radionuclide directly to tumor cells that express HLA-DR antigen, thereby this agent may be used in radioimmunotherapy of cancers.
A radioimmunoconjugate of a murine monoclonal antibody, MoAb Lym-1, labeled with indium 111 (In-111). MoAb Lym-1 recognizes an epitope of the histocompatibility antigen HLA-DR, which is over-expressed on most B-cell lymphomas. In-111 MoAb Lym-1 emits gamma radiation and X-Ray photons that can be captured by gamma camera allowing imaging of tumor cells that express HLA-DR antigen.
A tumor associated antigen derived from the cell surface antigen of lung cancer cells. Lung tumor associated antigen could be used as a diagnostic marker or as a form of immunotherapy targeted against lung cancer cells.
A molecular abnormality indicating rearrangement of the BCL2 gene.
A molecular abnormality indicating rearrangement of the BCL6 gene.
A molecular abnormality referring to the loss of at least one copy of the CDKN2A gene.
A term used to describe the workflow progression of a document or the state of the project or activity in terms of being finished, concluded, or made whole.
A finding indicating the spread of cancer to regional or distant lymph node(s).
A molecular abnormality indicating rearrangement of the MYC gene.
Duplication of the long arm of chromosome 18 with variable abnormalities, including intra-uterine growth retardation; characteristic facies with malformed ears, micrognathia, and prominent occiput; heart malformations; and psychomotor retardation.
The core phenotype of Elsahy-Waters syndrome consists of brachycephaly, facial asymmetry, marked hypertelorism, proptosis, blepharochalasis, midface hypoplasia, broad nose with concave nasal ridge, and prognathism; radicular dentin dysplasia with consequent obliterated pulp chambers, apical translucent cysts, recurrent infections, and early loss of teeth; vertebral fusions, particularly at C2-C3; and moderate mental retardation. Skin wrinkling over the glabellar region seems common, and in males, hypospadias has always been present. Inter- and intrafamilial variability has been reported regarding the presence of vertebral fusions, hearing loss,and dentigerous cysts. Midface hypoplasia, facial asymmetry, progressive dental anomalies, and impaired cognitive development become more evident in adulthood (Castori et al., 2010).
Limitation of independent operation of wheelchair within environment.
Applies to an individual who needs help in moving from bed to chair or requires a complete transfer.
Limitation of independent movement from one bed position to another.
Extension of the number of postoperative days required to initiate and perform activities that maintain life, health, and well-being.
Cyclical, recurring, and potentially progressive pattern of pervasive sadness experienced (by a parent, caregiver, individual with chronic illness or disability) in response to continual loss, throughout the trajectory of an illness or disability.
The potassium salt of hetacillin, a semi-synthetic penicillin antibiotic with bactericidal activity. Hetacillin is a prodrug that is converted to ampicillin via esterases. Ampicillin binds to and inactivated penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, thereby preventing the cross-linkage of peptidoglycans, which are critical components of the bacterial cell wall. This leads to an interruption of the bacterial cell wall and causes bacterial cell lysis.
A Malignant mesothelioma originating from cells of the pleura (the thin layer of mesothelium lining the lungs). Pleural mesothelioma is the most common form of mesothelioma.
Deletion of the short arm of chromosome 11 with a variable phenotype: Congenital absence of the iris, genitourinary abnormalities and mental retardation known as aniridia-ambiguous genitalia-mental retardation (AGR) triad; Wilms tumor-aniridia-ambiguous genitalia-mental retardation (WAGR) syndrome; Wilms tumor associated with congenital absence of the iris, genitourinary abnormalities, hemihypertrophy, mental retardation, and other anomalies termed AWTA;
Oculodentodigital syndrome is characterized by a typical facial appearance and variable involvement of the eyes, dentition, and fingers. Characteristic facial features include a narrow, pinched nose with hypoplastic alae nasi, prominent columella and thin anteverted nares together with a narrow nasal bridge, and prominent epicanthic folds giving the impression of hypertelorism. The teeth are usually small and carious. Typical eye findings include microphthalmia and microcornea. The characteristic digital malformation is complete syndactyly of the fourth and fifth fingers (syndactyly type III) but the third finger may be involved and associated camptodactyly is a common finding (summary by Judisch et al., 1979). Neurologic abnormalities are sometimes associated (Gutmann et al., 1991), and lymphedema has been reported in some patients with ODDD (Brice et al., 2013). See review by De Bock et al. (2013). Genetic Heterogeneity of Oculodentodigital Syndrome An autosomal recessive form of ODDD (257850) is also caused by mutation in the GJA1 gene, but the majority of cases are autosomal dominant.
The uterus is not entirely emptied of products of conception following spontaneous, medical or operative pregnancy termination.
An herbal extract prepared from the plant Hypericum perforatum (St. John's wort) with photodynamic, antineoplastic, and antidepressant activities. Hypericin, one of the active compounds found in Hypericum perforatum, is a photosensitizer that, when exposed to a particular wavelength and intensity of light, may induce tumor cell apoptosis. Another compound, hyperforin, induces caspase-dependent apoptosis in certain tumor cell lines. Hypericum perforatum preparations may also stimulate the activity of cytochrome P450 enzymes and P-glycoprotein drug transporters, resulting in increased metabolism and decreased efficacy of various chemotherapeutic agents and other drugs.
The 21-acetate derivative of desoxycorticosterone.
A sodium salt form of suramin, a polysulphonated naphthylurea with potential antineoplastic activity. Suramin blocks the binding of various growth factors, including insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor growth factor-beta (TGF-beta), to their receptors, thereby inhibiting endothelial cell proliferation and migration. This agent also inhibits vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis; retroviral reverse transcriptase; uncoupling of G-proteins from receptors; topoisomerases; cellular folate transport; and steroidogenesis.
A combination drug containing hydrochlorothiazide and triamterene used as a diuretic.
A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation.
An abnormal increase in the level of triglycerides in the blood. [HPO:probinson]
Product of the CANNABIS plant, CANNABINOIDS, or synthetic derivatives thereof, used in the treatment of a wide range of clinical symptoms.
Adverse psychological and behavioral reactions caused by the pressures and demands of employers or clients or other factors, such as the physical environment of the workplace, WORKPLACE VIOLENCE; or WORKPLACE BULLYING.
Outcomes that describe an individual's ideas and perceptions that influence health behavior
A form of liver inflammation caused by the hepatitis G virus.
A cognitive and neurological disorder due to fetal intrauterine exposure to maternal alcohol consumption. Typically, this presents without facies or other growth abnormalities.
A status of being neither employed nor unemployed for example students, the retired, carers and also those who are not in work or seeking work.
Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.
A personality trait characterized by a person's striving for flawlessness and setting excessively high performance standards, accompanied by overly critical self-evaluations and concerns regarding others' evaluations.
A hematology test result that indicates the presence of higher than normal platelet counts in the peripheral blood.
Spondylolysis, the cause of which is present from birth.
A benign epithelial skin tumor manifesting as a slightly elevant circular plaque or nodule with a red, pink or brown color and a diameter up to 22 mm.
Kidney damage that results from chronically elevated blood pressure; complications include glomerular damage resulting in proteinuria and hematuria.
A birth defect due to malformation of the URETHRA in which the urethral opening is below its normal location. In the male, the malformed urethra generally opens on the ventral surface of the PENIS or on the PERINEUM. In the female, the malformed urethral opening is in the VAGINA.
A carcinoma that arises from the ear. Representative examples include ceruminous adenocarcinoma and squamous cell carcinoma of the external ear and adenocarcinoma of the middle ear.
A carcinoma that arises from any of the structures of the eye.
A pathologic process that has spread from its original site of growth to multiple distant anatomic sites.
A question about an individual feeling emotional, such as angry or upset.
Gluten is a protein found in wheat, rye, and barley. It is found mainly in foods but may also be in other products like medicines, vitamins, and supplements. People with gluten sensitivity have problems with gluten. It is different from celiac disease, an immune disease in which people can't eat gluten because it will damage their small intestine. Some of the symptoms of gluten sensitivity are similar to celiac disease. They include tiredness and stomachaches. It can cause other symptoms too, including muscle cramps and leg numbness. But it does not damage the small intestine like celiac disease. Researchers are still learning more about gluten sensitivity. If your health care provider thinks you have it, he or she may suggest that you stop eating gluten to see if your symptoms go away. However, you should first be tested to rule out celiac disease. Dept. of Health and Human Services Office on Women's Health .
A cough that does not produce phlegm or mucus.
A carcinoma that arises from the cervix and is characterized by the lack of specific cellular differentiation.
Any problem arising from the use of a medical device.
A polypoid adenoma that arises from and protrudes into the lumen of the colon. Epithelial dysplasia is always present. According to the architectural pattern it is classified as tubular, tubulovillous, or villous.
Abnormal finding in a diagnostic test or assay. []
A lesion characterized by the proliferation of atypical or dysplastic cells without evidence of stromal invasion.
A bacterial infection of the stomach, caused by Helicobacter pylori. It is associated with the development of peptic ulcer and mucosa-associated lymphoid tissue lymphoma.
Geographic separation of members of a family.
An abnormality of the hematopoietic system.
A question about whether an individual feels or felt worried.
A lesion of the skin that is located in a specific region rather than being generalized.
Stage 0 includes: (Tis, N0, M0). Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
A radioactive isotope of phosphorus with beta particle-emitting radiocytotoxic activity. Emitted by phosphorus P32, beta particles directly damage cellular DNA and, by ionizing intracellular water to produce several types of cytotoxic free radicals and superoxides, indirectly damage intracellular biological macromolecules, resulting in tumor cell death.
A synthetic androgen analogue. Exemestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the conversion of cholesterol to pregnenolone and the peripheral aromatization of androgenic precursors into estrogens. (NCI04)
A class of disorders that encompasses conditions resulting from a congenital, familial hereditary trait or genetic abnormality as is manifested by a characteristic set of symptoms and signs.
Any deviation from the normal structure or function of the blood or lymphatic system that is manifested by a characteristic set of symptoms and signs.
Any deviation from the normal structure or function of the ear or labyrinth that is manifested by a characteristic set of symptoms and signs.
A non-neoplastic or neoplastic disorder that affects the respiratory system or the thorax including the mediastinum and the heart.
A class of disorders that encompasses conditions occurring as a result of metabolic dysfunction or deviation from the normal nutritional requirements.
A class of disorders that encompasses conditions of a general kind that result from a disease, the treatment of disease or administration of treatment at a particular site and are manifested by a characteristic set of symptoms and signs.
A class of conditions associated with pregnancy, puerperium and perinatal status.
Any deviation from the normal structure or function of the reproductive system or breast that is manifested by a characteristic set of symptoms and signs.
The development of a problematic medical situation that occurs during pregnancy.
The disposition to develop an allergic reaction, the allergic reaction itself or its consequences.
A hemorrhagic disorder that is caused by pathologic changes in the vasculature.
A change from the patient's baseline sleeping pattern, in the hours slept and/or an alteration/dysfunction in the stages of sleep.
Abnormal secretion of hormones in conjunction with neoplastic growth occurring anywhere in the body.
A hormone producing pituitary gland tumor, associated with a hormonal syndrome.
Infections with species in the genus PNEUMOCYSTIS, a fungus causing interstitial plasma cell pneumonia (PNEUMONIA, PNEUMOCYSTIS) and other infections in humans and other MAMMALS. Immunocompromised patients, especially those with AIDS, are particularly susceptible to these infections. Extrapulmonary sites are rare but seen occasionally.
Any disorder involving the peritoneal and retroperitoneal space.
Bleeding originating in and behind the tissues that line the wall of the abdominal cavity, intestine, and mesentery.
A disorder that affects the surface of the tooth.
A term that refers to disorders that result in pain and abnormal sensation in the teeth and/or periodontal tissues.
An infectious process affecting the esophagus.
An infectious process affecting the peritoneum.
A blood pressure elevation after 20 weeks of gestation in the absence of either proteinuria or systemic findings like thrombocytopenia, impaired liver function, progressive renal insufficiency, pulmonary edema or the new-onset of cerebral or visual disturbances.
A thyroid gland disorder present at birth. It includes thyroid gland aplasia and thyroid gland hypoplasia, both result in hypothyroidism.
Hemorrhagic and thrombotic disorders that occur as a consequence of inherited abnormalities in blood coagulation.
A hypertensive disorder that develops during pregnancy.
An acquired anemia resulting from immune-mediated destruction of the red blood cells. Causes include autoimmune disorders, blood transfusions, and drugs.
An increase in the concentration of red blood cells (hemoglobin) that is not caused by polycythemia vera.
A disorder characterized by reduced blood flow to the skin.
A non-metastasizing cartilaginous matrix-producing neoplasm characterized by the presence of neoplastic chondrocytes. Representative examples include osteochondroma and chondroma.
A sleep disorder (insomnia, hypersomnia, or parasomnia) for which there is strong physiological evidence that the disorder is etiologically linked to a general medical condition.
A classic form of congenital adrenal hyperplasia that is characterized by severe 21-hydroxylase deficiency, resulting in glucocorticoid and mineralocorticoid deficiency, without clinically significant salt wasting, and androgen excess, which causes virilization in female infants.
A laboratory test result which indicates increased levels of cardiac troponin T in a biological specimen.
A disorder that is caused by pathologic changes in the glomerular vasculature.
A laboratory test result which indicates increased levels of cardiac troponin I in a biological specimen.
A usually terminal event in the clinical course of lymphomas. The term indicates the presence of atypical, clonal (malignant) lymphocytes (lymphoma cells) in the peripheral blood. --2003
A high level of the degree to which oxygen is bound to hemoglobin given as a percentage calculated by dividing the maximum oxygen capacity into the actual oxygen content and multiplying by 100. Oxygen saturation usually is measured using pulse oximetry.
A severe acute inflammatory response affecting the hands and feet of individuals with with sickle cell disease, sickle cell-hemoglobin C disease or sickle cell-beta-thalassemia. It is caused by vaso-occlusive episodes leading to ischemia and finally infarction of the distal portions of the extremities. Clinical signs of pain, swelling and tenderness of digits usually begin in early childhood and may be the initial manifestations of sickle cell anemia. Clinical course is self-limited with instances typically lasting a few weeks and occurring during sickling crises. An initial episode before the age of 1 strongly correlates with a more severe disease course.
A carcinoma of the hypopharynx that arises from the postcricoid region.
Abnormally high levels of insulin in the blood.
Compression of the spinal cord in the cervical region, generally manifested by paresthesias and numbness, weakness, difficulty walking, abnormalities of coordination, and neck pain or stiffness.
A laboratory test result which indicates an increased level of alkaline phosphatase in a biological specimen.
Insomnia that is made worse by other factors, including pain, physiological or psychological disorders, external causes, or pharmacologic interventions.
A rare benign adipose tissue neoplasm located within the lumen of a bronchus. It is predominantly found in males and usually originates within the fatty tissue between bronchial cartilage. May cause irreversible pulmonary damage distally. Two-thirds of the tumors occur on the right side and most are located on the first three subdivisions of the tracheobronchial tree.
Pericarditis caused by the infiltration of the pericardium by a malignant neoplasm. The diagnosis is based on the cytological examination of pericardial fluid or the histologic examination of pericardial tissue.
An impairment of the structure or function of the blood vessels which carry blood away from the heart.
A flare of acne which may be precipitated by variety of factors, including hormonal activity, stress, oils and oily cosmetics, sweat, overwashing, and certain foods and drugs.
A benign or malignant neoplasm that affects the retro-orbital region.
An increase in the duration or intensity of epileptic symptoms in the setting of chronic epilepsy.
A benign condition in which the circulating AMYLASES are of high molecular masses, macroamylases. Macroamylases are amylase-plasma protein complexes, usually with immunoglobulins. Macroamylases cannot be cleared by the renal glomeruli.
A neoplasm that arises from the hair follicle and does not metastasize to other anatomic sites.
A laboratory test result which indicates a decreased glomerular filtration rate.
An decreased concentration of low-density lipoprotein cholesterol in the blood. [HPO:gcarletti]
A carcinoma that arises from the penis. Risk factors include phimosis and human papillomavirus infection. The majority of penile carcinomas are squamous cell carcinomas. The most frequent clinical presentation is an irregular mass in the glans of the penis. Treatment includes surgical management and radiation therapy.
A laboratory test result which indicates decreased levels of corticotrophin in the blood.
A laboratory test result which indicates decreased levels of CD4 lymphocytes in a biospecimen.
An abnormality of the function of the electrical signals with which peripheral nerve cells communicate with each other or with muscles.
A variation from the normal heart rhythm in a fetus.
Acute inflammation of the larynx caused by viruses, including rhinovirus, influenza virus, parainfluenza virus, and adenovirus.
A laboratory test result demonstrating an increased ratio of the patient's prothrombin time to a control sample.
A deviation from the normal circulating concentration of ferritin. Ferritin concentration can be measured in serum or plasma.
Facial diplegia (that is, bilateral facial palsy) with congenital onset.
Discrete, small lesions present in the cornea as a result of corneal inflammation and, in some cases, after soft contact lens wear especially extended-wear lenses.
A melanoma affecting the retinal portion of the eye. --2003
An x-ray of the carotid arteries that reveals normal results.
An x-ray of the cerebral arteries that reveals normal results.
An x-ray of the coronary arteries that reveals normal results.
A laboratory test result which indicates abnormal levels of antidiuretic hormone in the blood.
A laboratory test result which indicates abnormal levels of gonadotrophin hormone in the blood.
A laboratory test result which indicates abnormal levels of prolactin hormone in the blood.
A papillary tumor originating in the renal pelvis.
A disorder caused when there is a Rh-factor blood-type incompatibility between the mother and fetus, and the mother's immune system forms antibodies that attack the red blood cells of her unborn child. This disorder can only occur if the mother is Rh-negative and the fetus is Rh-positive.
Diethylstilbestrol (DES) syndrome is a set of signs reported in offspring (children and grandchildren) of women exposed to DES during pregnancy with manifestations of reproductive tract malformations, decreased fertility and increased risk of developing clear cell carcinoma of the vagina and cervix in young women. Reproductive malformations reported in DES syndrome include small, T-shaped uteri and other uterotubal anomalies that increase the risk of miscarriages in women and epididymal cysts, microphallus, cryptorchidism, or testicular hypoplasia in men.
A decrease in the number of neutrophils in the peripheral blood.
A laboratory test result indicating an abnormal increase in the number of lymphocytes in the peripheral blood, effusions, or bone marrow.
The reemergence of Waldenstrom macroglobulinemia after a period of remission.
A finding indicating the presence of a lower than expected number of spermatozoa in the semen.
A capillary or cavernous hemangioma arising from the breast.
An abnormally increased count of basophils per volume in the blood circulation. []
A pulmonary function test result indicating an abnormal vital capacity as compared to the predicted value.
Decreased blood supply to the small or large intestine due to narrowing or blockage of a visceral (mesenteric) artery. The ischemia results to the damage of the intestinal tissues. It may be chronic, caused by atherosclerosis or acute, secondary to the formation of a thrombus or embolus in the mesenteric arterial lumen. In chronic ischemia, patients present with abdominal pain manifested in a short time after a meal and weight loss. In acute ischemia, patients present with sudden and acute abdominal pain, nausea and vomiting, and blood in the stool.
A regionally-limited response to an antigen, which may include inflammation, induration, erythema, pruritus or pain.
Stage II includes: Any pT/TX, N1-3, M0, SX. pTX: Primary tumor cannot be assessed. N1: Metastasis with a lymph node mass 2 cm or less in greatest dimension; or multiple lymph nodes, none more than 2cm in greatest dimension. N2: Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, any one mass greater than 2 cm but not more than 5 cm in greatest dimension. N3: Metastasis with a lymph node mass more than 5 cm in greatest dimension. M0: No distant metastasis. SX: Marker studies not available or not performed. (AJCC 6th and 7th eds.)
An overwhelming, irrational, and persistent fear of contracting Acquired Immune Deficiency Syndrome.
An abnormal tract between the urinary system and the anterior surface of the gynecologic structures. These include vesico-vaginal, urethro-vaginal, uretero-vaginal, vesico-uterine, uretero-uterine, vesico-cervical, vesico-utero-vaginal fistulae.
A carcinoma that infiltrates the breast parenchyma. The vast majority are adenocarcinomas arising from the terminal ductal lobular unit (TDLU). Often, the invasive adenocarcinoma co-exists with ductal or lobular carcinoma in situ. It is the most common carcinoma affecting women.
A category of psychiatric disorders which are the direct physiologic consequence of a general medical condition.
Diabetes complications in which VENTRICULAR REMODELING in the absence of CORONARY ATHEROSCLEROSIS and hypertension results in cardiac dysfunctions, typically LEFT VENTRICULAR DYSFUNCTION. The changes also result in myocardial hypertrophy, myocardial necrosis and fibrosis, and collagen deposition due to impaired glucose tolerance.
The reemergence of inflammatory carcinoma of the breast after a period of remission
Inflammatory breast carcinoma is classified as AJCC Stage IIIB (T4d) unless other criteria indicate more advanced staging.
An inflammatory carcinoma of the breast that has spread to other anatomic sites.
An abnormally small number of lymphocytes in the circulating blood.
Abnormal result of a test designed to test an individual's central and peripheral vision by determining the ability of the individual to perceive objects at differing locations of the visual field.
An anomaly in the volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time.
An elevation in the total-iron binding capacity, which measures how much serum iron is bound if an excess of radioactive iron is added. A high TIBC corresponds to a high transferrin concentration. The latent (or free) iron binding capacity is the difference between the TIBC and the measured serum iron, corresponding to the transferrin not bound to iron, i.e., free iron binding capacity.
A painful sensation caused by the tumor growth.
Abnormal reduction in the count of eosinophils in the blood per volume. [HPO:probinson]
This term refers to an abnormally increased susceptibility to bruising (purpura, petechiae, or ecchymoses).
A seizure disorder that is present at the time of birth.
A type of diabetes mellitus related not to lack of insulin but rather to lack of response to insulin on the part of the target tissues of insulin such as muscle, fat, and liver cells. This type of diabetes is typically associated with increases both in blood glucose concentrations as will as in fasting and postprandial serum insulin levels.
The reemergence of nasal type NK/T-cell lymphoma after a period of remission.
Conjunctivitis that is characterized by the formation of papillae on the palpebral conjunctiva.
A malignant neoplasm that affects the liver parenchyma, bile ducts, and gallbladder. Representative examples include hepatocellular carcinoma, intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder carcinoma.
A malignant tumor that has spread to the adrenal gland from an adjacent or distant anatomic site. The majority of cases are metastatic carcinomas, and less frequently lymphomas.
A benign or malignant neoplasm that affects the liver parenchyma, bile ducts, and gallbladder. Representative examples of benign neoplasms include hepatocellular adenoma, bile duct adenoma, and gallbladder lipoma. Representative examples of malignant neoplasms include hepatocellular carcinoma, intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder carcinoma.
The spread of a malignant neoplasm from a primary site to an unspecified organ in the abdominal cavity.
Chronic myelomonocytic leukemia not growing; responding to treatment.
Dysplasia affecting the vasculature of the gastrointestinal tract.
An impediment to the flow of urine along the urinary tract, which is present at birth.
Excessive bleeding occurring after spontaneous miscarriage or therapeutic abortion.
A disorder characterized by impaired eyelid function.
Painful, localized rash caused by reactivation of latent varicella zoster virus residing in nerve cell bodies, with resulting infection of the skin in the region supplied by the affected nerve.
Localized rash characterized by grouped vesicles or pustules on an erythematous base that is caused by herpes simplex virus infection.
A genitourinary infection that is caused by Neisseria gonorrhoeae.
A neurological syndrome characterized by distorted perceptions of shape, loss of sense of time, and visual, auditory, and tactile hallucinations.
Lightening or darkening of the lips from their usual coloring.
An increase in the concentration of blood cells resulting from the loss of plasma or water from the blood stream.
A category of non-neoplastic disorders that affect the blood vessels in the lungs. Representative examples include pulmonary embolism, pulmonary hypertension, and arteriovenous malformations.
A granuloma that develops in the urinary bladder.
A laboratory test result indicating low production of erythrocytes, leukocytes and/or thrombocytes from the bone marrow.
A hormone producing pituitary gland adenoma, associated with a hormonal syndrome.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the cecum. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A usually slow-growing neuroendocrine tumor affecting the prostate gland.
Gastroenteritis resulting from an infection with enterovirus.
An infection that is caused by human herpesvirus-6.
Dislodgement, breakdown, or other malfunction of an artificial cardiac pacemaker, chemotherapy port, drip infusion valve, or similar implanted diagnostic or therapeutic device as a result of unconscious or habitual manipulation by the patient.
Device and/or fragments of device are embedded in patient's vessel and/or plaque.
A granuloma that forms in response to silicone exposure.
Complications of intraocular lens surgery; usually refers to intraocular lens contact with cornea, can be intermittent or chronic.
A group of disorders involving predominantly the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the RETINA; RETINAL PIGMENT EPITHELIUM; BRUCH MEMBRANE; CHOROID; or a combination of these tissues.
A brain hemorrhage caused by an intracranial tumor.
A disorder that is caused by pathologic changes in the spinal vasculature.
The reemergence of anal canal carcinoma in HIV-positive patients after a period of remission.
The reemergence of colorectal carcinoma after a period of remission.
An esophageal carcinoma which has reappeared after a period of remission or after presumed treatment.
An esophageal adenocarcinoma which has reappeared after a period of remission or after presumed treatment.
Stage II includes: IIA (T2, N0, M0, G3); IIB (T3, N0, M0, Any G); (T1-2, N1, M0, Any G). T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. M0: No distant metastasis. G3: Poorly differentiated. (AJCC 7th ed.)
Stage 0 includes: Tis (HGD), N0, M0, G1,GX. Tis: High-grade dysplasia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. (AJCC 7th ed.)
Stage I includes: IA (T1, N0, M0, G1-2, X); IB (T1, N0, M0, G3); (T2, N0, M0, G1-2, GX). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. G2: Moderately differentiated. G3: Poorly differentiated. GX: Grade cannot be assessed-stage grouping as G1. (AJCC 7th ed.)
Stage III includes: IIIA (T1-2, N2, M0, Any G); (T3, N1, M0, Any G); (T4a, N0, M0, Any G); IIIB (T3, N2, M0, Any G); IIIC (T4a, N1-2, M0, Any G); (T4b, Any N, M0, Any G); (Any T, N3, M0, Any G). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T4a: Resectable tumor invading pleura, pericardium, or diaphragm. T4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
An esophageal squamous cell carcinoma which has reappeared after a period of remission or after presumed treatment.
Stage 0 includes: Tis (HGD), N0, M0, G1, GX, Tumor location: Any. Tis: High-grade dysplasia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage I includes: IA (T1, N0, M0, G1, GX, Tumor location: Any); IB (T1, N0, M0, G2-3, Tumor location: Any); (T2-3, N0, M0, G1, GX, Tumor location: Lower, X). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage II includes: IIA (T2-3, N0, M0, G1, GX, Tumor location: Upper, middle); (T2-3, N0, M0, G2-3, Tumor location: Lower, X); IIB (T2-3, N0, M0, G2-3, Tumor location: Upper, middle); (T1-2, N1, M0, Any G, Tumor location: Any). T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage III includes: IIIA (T1-2, N2, M0, Any G, Tumor location: Any); (T3, N1, M0, Any G, Tumor location: Any); (T4a, N0, M0, Any G, Tumor location: Any); IIIB (T3, N2, M0, Any G, Tumor location: Any); IIIC (T4a, N1-2, M0, Any G, Tumor location: Any); (T4b, Any N, M0, Any G, Tumor location: Any); (Any T, N3, M0, Any G, Tumor location: Any). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T4a: Resectable tumor invading pleura, pericardium, or diaphragm. T4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Carcinoma of the pancreas that is not amenable to surgical removal.
The reemergence of pancreatic carcinoma after a period of remission.
Carcinoma of the pancreas amenable to surgical removal.
The reemergence of rectosigmoid carcinoma after a period of remission.
A carcinoma that arises from the small intestine and it has metastasized to other anatomic sites.
Carcinoma of the small intestine not amendable to resection.
The reemergence of small intestine carcinoma after a period of remission.
Carcinoma of the small intestine amendable to resection.
Extrahepatic bile duct carcinoma that is amenable to surgical removal.
A malignant neoplasm that affects the liver and it is not amenable to surgical resection.
The reemergence of liver carcinoma after a period of remission.
A malignant neoplasm that affects the liver and it is amenable to surgical resection.
Hepatoblastoma not amenable to surgical removal.
Hepatoblastoma amenable to surgical removal.
The reemergence of hepatoblastoma after a period of remission.
The reemergence of chronic lymphocytic leukemia after a period of remission.
Risk: Intermediate; Findings: Lymphocytosis, adenopathy, and enlarged spleen and/or liver; Survival (months): 72. (from AJCC 8th Ed.)
Risk: High; Findings: Lymphocytosis and platelets less than 100,000/microliter; Survival (months): 30. (from AJCC 8th Ed.)
The reemergence of lymphocyte-depleted classical Hodgkin lymphoma after a period of remission.
Lymphocyte-depleted classical Hodgkin lymphoma that is resistant to treatment.
Lymphoplasmacytic lymphoma resistant to treatment.
Adult T-cell leukemia/lymphoma that is resistant to treatment.
Anaplastic large cell lymphoma resistant to treatment.
Ann Arbor Classification: Stage I: Involvement of a single lymph node region (I); or localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE).- 2003
Ann Arbor Classification. Stage III: Involvement of lymph node regions on both sides of the diaphragm (III), which also may be accompanied by extralymphatic extension in association with adjacent lymph node involvement (IIIE) or by involvement of the spleen (IIIS) or both (IIIE,S). - 2003
The reemergence of T-cell non-Hodgkin lymphoma after a period of remission.
T-cell non-Hodgkin lymphoma resistant to treatment.
Nasal type extranodal NK/T-cell lymphoma that does not respond to treatment.
Angioimmunoblastic T-cell lymphoma resistant to treatment.
The reemergence of angioimmunoblastic T-cell lymphoma after a period of remission
The reemergence of enteropathy-associated T-cell lymphoma after a period of remission.
Enteropathy-associated T-cell lymphoma that is resistant to treatment.
Ann Arbor Classification: Stage I: Involvement of a single lymph node region (I); or localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE).-2003
The reemergence of mycosis fungoides after a period of remission.
Mycosis fungoides resistant to treatment.
Peripheral T-cell lymphoma not otherwise specified resistant to treatment.
The reemergence of T lymphoblastic leukemia/lymphoma after a period of remission.
T-lymphoblastic leukemia/lymphoma resistant to treatment
Ann Arbor Classification: Stage I: Involvement of a single lymph node region (I); or localized involvement of a single extralymphatic organ or site in the absence of any lymph node involvement (IE) (Rare in Hodgkin lymphoma). - 2003
Ann Arbor Classification: Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II); or localized involvement of a single extralymphatic organ or site in a with regional lymph node involvement with or without involvement of other lymph node regions on the same side of the diaphragm (IIE). - 2003
Ann Arbor Classification: Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement; or isolated extralymphatic organ involvement in the absence of adjacent regional lymph node involvement, but in conjunction with disease in distant site(s); or any involvement of the liver or bone marrow, or nodular involvement of the lungs(s). - 2003
The reemergence of non-Hodgkin lymphoma after a period of remission.
A non-Hodgkin lymphoma which does not respond to treatment.
The reemergence of non-Hodgkin lymphoma transformed after a period of remission.
A malignant mesothelioma extensively involving the pericardium.
The reemergence of malignant mesothelioma in the pericardium after a period of remission.
A malignant mesothelioma that arises from the peritoneum and has spread in the abdominal cavity. It may result in bowel obstruction.
The reemergence of malignant peritoneal mesothelioma after a period of remission
Malignant mesothelioma that arises from the pleura and is classified as stage II, stage III, or stage IV.
A malignant mesothelioma that arises from the pleura with the gross appearance of a localized nodular lesion without gross or microscopic evidence of diffuse pleural involvement.
The reemergence of pleural malignant mesothelioma after a period of remission.
An angiosarcoma that has spread to another anatomical site.
A malignant vascular neoplasm contained in the anatomical site where it initially manifested.
The reemergence of angiosarcoma after a period of remission.
A malignant hemangiopericytoma which has spread to another anatomical site.
A rare malignant mesenchymal neoplasm that is believed to have its origin in smooth muscle derived pericytes without evidence of metastases.
A rare malignant mesenchymal neoplasm, believed to have its origin in smooth muscle derived pericytes, which has recurred after treatment.
A lesion which is characterized by an irregularly nodular opalescent wall which has caused it to be termed a ""pearly tumor"". The Intramural contents are soft and waxy with a variable amount of cholesterol.
A germinoma that arises from the pineal gland.
Retinoblastoma involving both eyes. This occurs in the majority of patients with the inherited variant. A minority of patient with bilateral retinoblastoma were found to have involvement of the pineal gland as well.
A retinoblastoma that only involves a single eye.
A rhabdoid tumor that arises from the kidney. It occurs in children and it is associated with abnormalities of chromosome 22. It is characterized by the presence of cells with a large eccentric nucleus, prominent nucleolus, and abundant cytoplasm. The prognosis is poor.
A malignant neoplasm of the urethra that has spread to nearby tissues but has not spread to distant sites.
A malignant neoplasm of the ureter without spread to any other region.
Stage III includes: (T3, N0, M0); IIIA (T3a, N0, M0); IIIB (T3b, N0, M0); IIIC (T3c, N0, M0); (Any T, N1, M0). T3: Tumor involves one or both fallopian tubes, with peritoneal implants outside the pelvis. T3a: Microscopic peritoneal metastasis outside the pelvis. T3b: Macroscopic peritoneal metastasis outside the pelvis 2 cm or less in greatest dimension. T3c: Peritoneal metastasis outside the pelvis and more than 2 cm in diameter. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage I includes: T1, N0, M0. T1: Tumor confined to the vulva or vulva and perineum, 2cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.). - 2003
Stage II includes: T2, N0, M0. T2: Tumor confined to the vulva or vulva and perineum, more than 2cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, N0, M0); (T3, N1, M0). T3: Tumor of any size with contiguous spread to the lower urethra and/or vagina or anus. N1: Unilateral regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Carcinoma of the penis which has spread from its original site of growth to another anatomic site.
A carcinoma of the penis that reappears after a period of remission.
Stage I includes: T1a, N0, M0. T1a: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3-4). cN0: No palpable or visibly enlarged inguinal lymph nodes. pN0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: (T1b, N0, M0); (T2, N0, M0); (T3, N0, M0). T1b: Tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated. T2: Tumor invades corpus spongiosum or cavernosum. T3: Tumor invades urethra. cN0: No palpable or visibly enlarged inguinal lymph nodes. pN0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: IIIa (T1-3, N1, M0); IIIb (T1-3, N2, M0). T1: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3-4) or tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated. T2: Tumor invades corpus spongiosum or cavernosum. T3: Tumor invades urethra. cN1: Palpable mobile unilateral inguinal lymph node. pN1: Metastasis in a single inguinal lymph node. cN2: Palpable mobile multiple or bilateral inguinal lymph nodes. pN2: Metastasis in multiple or bilateral superficial inguinal lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
The reemergence of adenosquamous lung carcinoma after a period of remission.
The reemergence of large cell lung carcinoma after a period of remission.
The re-emergence of lung adenocarcinoma after a period of remission.
The re-emergence of squamous cell lung carcinoma after a period of remission.
A malignant epithelial neoplasm arising in the paranasal sinus.
The reemergence of carcinoma of the pharynx after a period of remission.
Stage I carcinoma of the pharynx according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Lung carcinoma that has re-emerged after a period of remission.
A small round cell tumor with neural differentiation which is confined to a specific area of the bone and has not spread to other parts of the skeleton.
A small round cell tumor of the bone with neural differentiation which has spread from its original site of growth to another anatomic site.
A small round cell tumor with neural differentiation arising from the bone. It may be associated with pain.
The reemergence of peripheral primitive neuroectodermal tumor of the bone after a period of remission.
A non-disseminated skeletal or extraskeletal chondrosarcoma.
A chondrosarcoma that has spread to a secondary anatomical site.
The reemergence of chondrosarcoma after a period of remission.
The reemergence of lentigo maligna after a period of remission
Reemergence of undifferentiated pleomorphic sarcoma after a period of remission.
An alveolar soft part sarcoma which has spread to another anatomic site.
An alveolar soft part sarcoma presently contained in the anatomical site where it initially manifested.
The reemergence of alveolar soft part sarcoma after a period of remission.
An epithelioid sarcoma which has spread to another anatomic site.
An epithelioid sarcoma presently contained in the anatomical site where it initially manifested.
The reemergence of epithelioid sarcoma after a period of remission
An Ewing sarcoma of the soft tissues which has spread from its original site of growth to another anatomic site.
An Ewing sarcoma of the soft tissues which is confined to its original site of growth without evidence of spread to another anatomic site.
Reemergence of extraskeletal Ewing sarcoma after a period of remission.
A soft tissue osteosarcoma which has spread to another anatomical site.
An osteosarcoma that arises from the soft tissue and remains confined to the primary anatomical site.
An osteosarcoma arising from the soft tissue.
The reemergence of extraskeletal osteosarcoma after a period of remission.
A fibrosarcoma that has spread to other anatomical sites.
A fibrosarcoma contained in the anatomical site where it initially manifested.
A leiomyosarcoma that has spread to other anatomical sites.
A leiomyosarcoma that arises from the anatomical part in which it presents and not due to metastasis from a different location.
The reemergence of leiomyosarcoma after a period of remission
A liposarcoma that has metastasized to a secondary site.
A liposarcoma that has not metastasized to secondary sites.
The reemergence of a malignant adipose tissue neoplasm after a period of remission.
The reemergence of rhabdomyosarcoma after a period of remission.
A synovial sarcoma that has metastasized to other anatomic sites.
Synovial sarcoma affecting an anatomic site as a primary tumor.
The reemergence of synovial sarcoma after a period of remission
An aggressive malignant mesenchymal neoplasm that arises from the liver and usually occurs in older children. It is composed of immature spindle, stellate, polymorphous, and giant cells.
An antiquated term that refers to the reemergence of either nodular lymphocyte predominant Hodgkin lymphoma or lymphocyte-rich classical Hodgkin lymphoma after a period of remission.
An antiquated term that refers either to nodular lymphocyte predominant Hodgkin lymphoma or to lymphocyte-rich classical Hodgkin lymphoma that is resistant to treatment.
Stage III adult Hodgkin disease means the involvement of lymph node regions on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an associated extralymphatic organ or site (IIIE), by involvement of the spleen (IIIS), or by involvement of both (IIIE + S). Stage III disease may be subdivided by anatomic distribution of abdominal involvement or by extent of splenic involvement. Stage III(1) indicates involvement that is limited to the upper abdomen above the renal vein. Stage III(2) indicates involvement of pelvic and/or para-aortic nodes. Five or more visible splenic nodules on a cut section constitutes extensive splenic involvement. Zero to four nodules is classified as minimal splenic disease. (from PDQ)
Stage IV adult Hodgkin disease means there is disseminated (multifocal) involvement of one or more extralymphatic organs, with or without associated lymph node involvement, or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement. (from PDQ)
The reemergence of mixed cellularity classical Hodgkin lymphoma after a period of remission.
Mixed cellularity classical Hodgkin lymphoma that is resistant to treatment.
The reemergence of nodular sclerosis classical Hodgkin lymphoma after a period of remission.
Nodular sclerosis classical Hodgkin lymphoma that is resistant to treatment.
The reemergence of B-cell non-Hodgkin lymphoma after a period of remission.
B-cell non-Hodgkin lymphoma that is resistant to treatment.
A non-Hodgkin lymphoma composed of monomorphic small, round B-lymphocytes in the lymph nodes. When the lymphoid process predominantly involves the bone marrow and the peripheral blood it is called chronic lymphocytic leukemia. (WHO, 2001)
The reemergence of small lymphocytic lymphoma after a period of remission.
B-cell small lymphocytic lymphoma that is resistant to treatment.
The reemergence of Burkitt lymphoma after a period of remission.
Burkitt lymphoma that is resistant to treatment.
The reemergence of diffuse large B-cell lymphoma after a period of remission.
Diffuse large B-cell lymphoma that is resistant to treatment.
Mantle cell lymphoma resistant to treatment.
A primary nodal B-cell non-Hodgkin lymphoma which morphologically resembles lymph nodes involved by marginal zone lymphomas of extranodal or splenic types, but without evidence of extranodal or splenic disease. (WHO, 2001)
Nodal marginal zone B-cell lymphoma resistant to treatment.
An uncommon type of lymphoma. It constitutes approximately 10% of cases of lymphoblastic lymphoma. Approximately 75% of cases reported in a literature review involved patients who were less than 18 years of age. The most commonly affected sites are the skin, bone, soft tissue, and lymph nodes. It has a high remission rate with a median survival of approximately 60 months. (WHO, 2001)
The reemergence of B lymphoblastic lymphoma after a period of remission.
B lymphoblastic lymphoma resistant to treatment.
The reemergence of mediastinal (thymic) large B-cell lymphoma after a period of remission.
Mediastinal (thymic) large B-cell lymphoma that is resistant to treatment.
An embryonal carcinoma that develops as a primary tumor in an anatomic site other than the testis or ovary.
An immature teratoma that develops as a primary tumor in an anatomic site other than the testis or ovary.
Choriocarcinoma that develops in the placenta. It is the rarest form of gestational choriocarcinoma. Metastases to the mother and infant may occur.
A recurrence of adenocarcinoma of the bladder after a period of remission.
Stage IV includes: (T4b, N0, M0); (Any T, N1-3, M0); (Any T, Any N, M1). T4b: Tumor invades pelvic wall, abdominal wall. N0: No regional lymph node metastasis. N1: Single regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node). N2: Multiple regional lymph node metastases in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node metastasis). N3: Metastasis to the common iliac lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage III includes: Any pT/TX, Any N, M1, SX. M1: Distant metastasis. SX: Marker studies not available or not performed. (AJCC 6th and 7th eds.)
The reemergence of bladder squamous cell carcinoma after a period of remission.
Stage I includes: pT1-4, N0, M0, SX. pT1: Tumor limited to the testis and epididymis without vascular/lymphatic invasion; tumor may invade into the tunica albuginea but not the tunica vaginalis. pT2: Tumor limited to the testis and epididymis with vascular/lymphatic invasion, or tumor extending through the tunica albuginea with involvement of the tunica vaginalis. pT3: Tumor invades the spermatic cord with or without vascular/lymphatic invasion. pT4: Tumor invades the scrotum with or without vascular/lymphatic invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. SX: Marker studies not available or not performed. (AJCC 6th and 7th eds.)
A malignant tumor predominantly affecting young men and often associated with cryptorchidism. Seminoma is the most frequently seen malignant testicular germ cell tumor, followed by embryonal carcinoma and yolk sac tumor.
Abnormal eating behaviors, including binge eating, compulsive eating, emotional eating, night eating, and self-induced vomiting, though not at a level that rises to the diagnosis of eating disorder.
A subtype of delusional disorder characterized by the central delusional theme that the individual's spouse or lover is unfaithful.
A subtype of delusional disorder characterized by the central delusional theme that another person (usually one of higher status) is in love with the individual.
A subtype of delusional disorder characterized by the central delusional theme that the individual has special worth, power, knowledge, or a special relationship to a famous person or deity.
A subtype of delusional disorder characterized by the central delusional theme that the individual has some physical defect or medical condition.
A subtype of delusional disorder applied when the dominant delusional theme cannot be clearly determined.
An anomaly of the pulse pressure, which is defined as the systolic pressured minus the diastolic pressure.
Increased amplitude of the pulse pressure (systolic blood pressure minus diastolic blood pressure).
An electrocardiographic finding of a change in cardiac electrical activity.
An electrocardiographic finding in which the QTc interval corrected for heart rate is prolonged. Thresholds for different age, gender, and patient populations exist. (CDISC)
An anomaly of the mobility of ejaculated sperm.
Any anomaly in the function of thrombocytes.
An anomaly in platelet form, ultrastructure, or intracellular organelles.
A decrease in any of the parameters used to measure the mechanical function of the lungs and upper airway.
A reduction from normal of the mean corpuscular volume, or mean cell volume (MCV) of red blood cells (usually defined as an MCV below 80 femtoliters). []
Larger than normal size of erythrocytes.
An abnormally reduced count of basophils per volume in the blood circulation. []
Any structural abnormality or abnormal count of basophils. [HPO:probinson]
An eosinophil abnormality. [HPO:probinson]
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue that is resistant to treatment.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue presenting as stage I disease.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue presenting as stage II disease.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue presenting as stage III disease.
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue presenting as stage IV disease.
A chronic, inflammatory skin condition characterized by raised, ring shaped eruptions occurring singly or in groups; often on the tops of the hands, feet, elbows, and knees. It is commonly seen in children and young adults, and in women twice as much as men.
An infectious process affecting the uterine cervix. Causative agents include Neisseria gonorrhoeae, Chlamydia trachomatis, human papillomavirus, and herpes simplex virus. Physical examination reveals an erythematous, raised lesion in the cervix and mucopurulent discharge.
An increased consentration of zinc in the blood.
A fetal position during delivery in which the head of the fetus is facing the mother's abdomen.
Inflammation of the alveoli of the lung.
The presence of multiple granulomata (small nodular inflammatory lesions containing grouped mononuclear phagocytes) in the lung.
Acute and progressive bronchopneumonia caused by Mycobacterium tuberculosis bacteria. It is characterized by widespread pulmonary patchy consolidations.
An infectious process that affects the brain and spinal cord tissues. It is usually caused by viruses.
Gallstones composed primarily of cholesterol, usually about 2-3 cm in length with an oval form and a yellow or green/brown color.
An abnormal localized widening (dilatation) of the tubular part of the ascending aorta. []
An abnormal localized widening (dilatation) of the aortic arch. []
A condition in which the hepatic venous outflow is obstructed anywhere from the small HEPATIC VEINS to the junction of the INFERIOR VENA CAVA and the RIGHT ATRIUM. Usually the blockage is extrahepatic and caused by blood clots (THROMBUS) or fibrous webs. Parenchymal FIBROSIS is uncommon.
Polycythemia resulting from dehydration.
A syndrome of immunologically mediated tissue damage that may occur following an allogeneic transplant, usually affecting the skin, liver, and GI tract. The onset is usually within one hundred days of transplantation or immunologic manipulation.
Chondrocalcinosis, or cartilage calcification, is a common condition that usually results from deposition of crystals of calcium pyrophosphate dihydrate (CPPD) in articular hyaline and fibro-cartilage. CPPD crystal deposition may be asymptomatic or associated with characteristic acute attacks ('pseudogout') or chronic arthritis. It can be detected radiographically. Chondrocalcinosis occurs in 3 forms: a primary hereditary form (e.g., CCAL2); a form associated with metabolic disorders (e.g., hyperparathyroidism, hemochromatosis, and hypomagnesemia), and a sporadic form, which may in some cases represent the hereditary form (summary by Hughes et al., 1995 and Richette et al., 2009). Genetic Heterogeneity of Chondrocalcinosis Another form of chondrocalcinosis (CCAL1; 600668) has been mapped to chromosome 8q.
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
A hemangioma that is not present at birth but develops later in life.
A sarcoma that arises from the skin. Representative examples include Kaposi sarcoma, angiosarcoma, lymphangiosarcoma, liposarcoma, and leiomyosarcoma.
An abnormal rise in the volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time.
A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual (DSM-IV). [DSM-IV:299.00, HPO:probinson]
A type of hyperbilirubinemia with neonatal onset.
Candidiasis that is persistent or long-standing in nature.
Increased pressure in both eyeballs due to obstruction of the outflow of aqueous humor.
A sensation of discomfort emanating from the inferiormost (verterbrochondral or vertebral) ribs.
A type of supraventricular tachycardia that originates in the atrioventricular node.
The kneecap normally is located within the groove termed trochlea on the distal femur and can slide up and down in it. Patellar subluxation refers to an unstable kneecap that does not slide centrally within its groove, i.e., a partial dislocation of the patella.
Any form of purpura in which the PLATELET COUNT is decreased. Many forms are thought to be caused by immunological mechanisms.
An abnormality of the pinna, which is also referred to as the auricle or external ear. [HPO:probinson]
An individual whose level of consciousness is such that he is not responsive to any stimulus.
An abnormal functionality of the thyroid gland.
Less serious form of hypersensitivity reaction which occurs in response to medicines, infections, or illness.
An infection that is caused by JC virus.
A deviation from normal concentrations of estradiol in the circulation.
An abnormal increased concentration of parathyroid hormone.
Lymph node infection by Mycobacterium avium or Mycobacterium intracellulare. It most often affects children and usually presents with cervical lymph node enlargement. It generally follows a benign clinical course.
The most common histologic type of breast carcinoma. Representative examples include invasive ductal carcinoma not otherwise specified, ductal carcinoma in situ, inflammatory carcinoma, secretory carcinoma, signet ring cell carcinoma, tubular carcinoma, invasive lobular carcinoma, and lobular carcinoma in situ.
Spinal nerve paralysis that is irreversible.
A type of cataract affecting the posterior pole of lens immediately adjacent to ('beneath') the Lens capsule.
A form of colorblindness in which only two of the three fundamental colors can be distinguished due to a lack of one of the retinal cone pigments.
Unprovoked explosive pathological sneezing.
Painful sensation in the pharyngolaryngeal region.
Coughing up and spitting out of an overproduction of mucus in the respiratory tract in reaction to a constantly recurring irritant.
Telangiectases (small dilated blood vessels) located near the surface of the skin of the face.
A reduced number of reticulocytes in the peripheral blood.
Bleeding between the conjunctiva and episclera in the absence of discharge or inflammation.
Trouble expectorating saliva or mucus from the respiratory tract.
Kidney damage resulting from uric acid precipitation within the renal tubules.
Inflammation of the glomeruli, in which all glomeruli are affected, resulting in renal failure.
A malignant neoplasm that affects the area of the nipple.
An abnormal accumulation of fluid beneath the skin on the palm of the hand.
A benign polypoid growth in the external or middle ear.
Any functional anomaly of the vocal cord. []
A benign or malignant neoplasm arising from the hair follicle.
A broad classification for humoral immunodeficiencies. These disorders may be caused by inadequate activation of progenitor B cells, defective class-switching or the effects of medications. Despite the potential for increased susceptibility to infection, these disorders are self-limited with eventual normalization of serum antibody levels.
Characterised by loss of oesophageal peristalsis and insufficient lower oesophageal sphincter relaxation in response to deglutition. A rare disease with no gender predilection, the peak incidence occurs between 30 and 60 years of age. Although the precise aetiology is unknown, it is often thought to be either autoimmune, viral immune, or neurodegenerative. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant aetiologic factor.
A granuloma that develops in response to Actinomycotic fungal infection.
A form of reactive arthritis that is associated with lesions on both the palms of the hands and the soles of the feet.
Damage to the liver tissue due to drug overdose.
An infection that arises secondary to catheter use.
A laboratory test result indicating an inheritable form of dysbetalipoproteinemia, in which there are excess intermediate-density lipoproteins in the blood.
Small, dome-shaped nodules without a prominent central vessel located on the conjunctiva. The lymphoid follicles are located in the subendothelial region of the conjunctiva. They consist of a germinal center that contains immature, proliferating lymphocytes, as well as a corona that contains mature lymphocytes and plasma cells.
Freezing of gait is defined as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. [PMID:23625316]
A condition of metabolic imbalance that is caused by complications of initially feeding a severely malnourished patient too aggressively. Usually occurring within the first 5 days of refeeding, this syndrome is characterized by WATER-ELECTROLYTE IMBALANCE; GLUCOSE INTOLERANCE; CARDIAC ARRHYTHMIAS; and DIARRHEA.
A syndrome observed in patients with acute promyelocytic leukemia treated with all-trans retinoic acid. It is characterized by weight gain, dyspnea, pleural and pericardial effusions, leukocytosis, and renal failure.
An infiltrating breast carcinoma with a relatively favorable prognosis. It is an uncommon carcinoma, accounting for less than 1% of all infiltrating breast carcinomas. It is well circumscribed, with soft cut surface and often of considerable size. Microscopically, the predominant growth pattern is syncytial with broad anastomosing bands or sheets of malignant cells. The malignant cells are round with abundant cytoplasm and vesicular nuclei. The sheets of malignant cells are associated with a marked lymphoplasmacytic infiltrate. Glandular or tubular structures are absent.
Uncontrolled episodes of crying, without apparent motivating stimuli.
A disorder characterized by the acute and sudden development of changes in attention, memory, language and/or perception that can be etiologically linked to the direct physiological consequences of a general medical condition.
A disorder involving memory impairment (either anterograde or retrograde) that is etiologically linked to the direct physiological consequence of a general medical condition. The memory impairment is not the result of a delirium or dementia.
Feigned coma or psychogenic coma. These patients appear comatose (i.e., unresponsive, unarousable, or both) but have no structural lesion, metabolic or toxic disorder.
Insomnia as a result of a physiological cause.
A laboratory test result which indicates abnormal levels of growth hormone in a biologic specimen.
An electrocardiographic finding of the Q axis from -30 to -90 degrees.
An abnormally decreased level of immunoglobulin E (IgE) in blood.
The reemergence of centroblastic lymphoma after a period of remission.
Centroblastic lymphoma, resistant to treatment.
A spectrum of non-invasive neoplastic lesions that arise from the terminal ductal lobular units of the breast. There is atypical small epithelial cell proliferation. Pagetoid involvement of the terminal ducts may or may not be present. In the minority of cases, there is a risk for subsequent development of invasive ductal or invasive lobular carcinoma.
Stage IV includes: (Any T, Any N, M1). M1: Distant metastasis. (AJCC 6th ed.) - 2003
The reemergence of a lip or oral cavity malignant neoplasm after a period of remission.
Reemergence of squamous cell carcinoma of the oral cavity after a period of remission.
An adenocarcinoma that arises from the exocrine pancreatic tissue and has metastasized to other anatomic sites.
An adenocarcinoma that arises from the small intestine and has metastasized to other anatomic sites.
The reemergence of duodenal carcinoma after a period of remission.
The reemergence of a malignant duodenal neoplasm after a period of remission.
Carcinoma of the duodenum amendable to surgical removal.
A carcinoma that arises from the extrahepatic bile ducts. It is characterized by the presence of glandular and squamous malignant epithelial components.
A morphologic variant of extrahepatic bile duct adenocarcinoma characterized by the presence of malignant glandular epithelium composed of clear cells.
An adenocarcinoma that arises from the extrahepatic bile ducts. It is characterized by the presence of extracellular mucin that constitutes more than fifty-percent of the tumor.
An adenocarcinoma that arises from the extrahepatic bile ducts. It is characterized by the presence of signet ring malignant epithelial cells.
A carcinoma that arises from the extrahepatic bile ducts. It is composed entirely by malignant squamous epithelial cells.
The reemergence of hepatocellular carcinoma after a period of remission
A neoplasm of lymphoblasts committed to the B-cell lineage, typically composed of small to medium-sized blast cells. When the neoplasm involves predominantly the bone marrow and the peripheral blood, it is called B acute lymphoblastic leukemia. When it involves nodal or extranodal sites, it is called B lymphoblastic lymphoma. (WHO, 2001)
Lymphomatoid granulomatosis characterized by the presence of occasional large lymphoid cells or immunoblasts in a polymorphous background. Necrosis is more commonly seen as compared to grade I lymphomatoid granulomatosis. By in situ hybridization, EBV-positive cells are readily seen.
A peripheral (mature) T-cell lymphoma presenting in the skin with patches/plaques and it is characterized by epidermal and dermal infiltration of small to medium-sized T-cells with cerebriform nuclei. Patients with limited disease generally have an excellent prognosis. In the more advanced stages, the prognosis is poor. (WHO, 2001) -- 2003
Mature T and NK neoplasms predominantly affecting the skin and the peripheral blood. Peripheral blood involvement by abnormal T-cells (cerebriform cells) is a late manifestation of mycosis fungoides, whereas it is the presenting finding in Sezary syndrome. --2003
The reemergence of mycosis fungoides/Sezary syndrome after a period of remission.
A malignant neoplasm arising from mesothelial cells in the pleura. It is characterized by the presence of neoplastic cells with an epithelioid appearance. In the majority of cases, the neoplastic epithelioid cells lack significant cytologic atypia; mitotic figures are infrequently seen. In a minority of cases, the neoplastic cells are poorly differentiated and there is evidence of nuclear atypia and increased mitotic activity.
The reemergence of a malignant bladder neoplasm after a period of remission.
The reemergence of bladder urothelial carcinoma after a period of remission.
Stage IV includes: (T4, N0, M0); (T4, N1, M0); (Any T, N2, M0); (Any T, Any N, M1). T4: Tumor invades beyond Gerota's fascia. N0: No regional lymph node metastases. N1: Metastasis in a single regional lymph node. N2: Metastasis in more than one regional lymph node. M0: No distant metastasis. M1: Distant metastasis. (AJCC 6th ed.)
The reemergence of transitional cell carcinoma in the urethra after a period of remission.
An adenocarcinoma which originated in the endometrium and has spread to another anatomic site.
An endometrioid adenocarcinoma that has spread from its original site of growth to another anatomic site.
An adenocarcinoma that arises from the vagina and has metastasized to other anatomic sites.
An adenocarcinoma that arises from the prostate gland and has spread to other anatomic sites.
Stage I includes: (T1a-c, N0, M0, PSA less than 10, Gleason equal or less than 6); (T2a, N0, M0, PSA less than 10, Gleason equal or less than 6); (T1-2a, N0, M0, PSA X, Gleason X). T1a: Tumor incidental histologic finding in 5% or less of tissue resected. T1b: Tumor incidental histologic finding in more than 5% of tissue resected. T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA). T2a: Tumor involves one-half of one lobe or less. cN0: No regional lymph node metastasis. pN0: No positive regional nodes. M0: No distant metastasis. Gleason Equal or Less than 6: Well differentiated (slight anaplasia). Gleason X: Gleason score cannot be processed. (AJCC 7th ed.)
Stage II includes: IIA (T1a-c, N0, M0, PSA less than 20, Gleason 7); (T1a-c, N0, M0, PSA equal or more than 10 and less than 20, Gleason equal or less than 6); (T2a, N0, M0, PSA less than 20, Gleason equal or less than 7); (T2b, N0, M0, PSA less than 20, Gleason equal or less than 7); (T2b, N0, M0, PSA X, Gleason X); IIB (T2c, N0, M0, Any PSA, Any Gleason); (T1-2, N0, M0, PSA equal or more than 20, Any Gleason); (T1-2, N0, M0, Any PSA, Gleason equal or more than 8). T1a: Tumor incidental histologic finding in 5% or less of tissue resected. T1b: Tumor incidental histologic finding in more than 5% of tissue resected. T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA). T2a: Tumor involves one-half of one lobe or less. T2b: Tumor involves more than one-half of one lobe, but not both lobes. T2c: Tumor involves both lobes. cN0: No regional lymph node metastasis. pN0: No positive regional nodes. M0: No distant metastasis. Gleason 7: Moderately differentiated (moderate anaplasia). Gleason Equal or Less than 6: Well differentiated (slight anaplasia). Gleason equal or more than 8: Poorly differentiated/undifferentiated (marked anaplasia). (AJCC 7th ed.)
Stage III includes: T3a-b, N0, M0, Any PSA, Any Gleason. cT3a: Tumor with extracapsular extension (unilateral or bilateral). pT3a: Tumor with extraprostatic extension or microscopic invasion of bladder neck. T3b: Tumor invades seminal vesicle(s). cN0: No regional lymph node metastasis. pN0: No positive regional nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: (T4, N0, M0, Any PSA, Any Gleason); (Any T, N1, M0, Any PSA, Any Gleason); (Any T, Any N, M1, Any PSA, Any Gleason). cT4: Tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall. pT4: Invasion of rectum, levator muscles, and/or pelvic wall. N1: Metastasis in regional lymph node(s). M1: Distant metastasis. (AJCC 7th ed.)
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (T4b, Any N, M0); (Any T, N3, M0); IVC: (Any T, Any N, M1). T4: (Supraglottis) T4a: Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. (Glottis) T4a: Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. (Subglottis) T4a: Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension. N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M1: Distant metastasis. (AJCC 6th ed.)
An aggressive morphologic variant of chondrosarcoma. It is composed of a low grade chondrosarcoma and a high grade non-cartilagenous sarcomatous component. Due to the aggressive nature of the disease, its prognosis is poor.
A type of basal cell carcinoma of the skin. It appears as a flesh-colored papule with telangiectatic vessels on its surface. It grows slowly; as it enlarges it becomes necrotic forming a central ulcer with raised borders.
A variant of basal cell carcinoma of the skin presenting as erythematous, often multiple patches. Morphologically, it is characterized by the presence of superficial lobules of basaloid cells projecting into the dermis. The basaloid cell lobules are surrounded by myxoid stroma and are usually confined to the papillary dermis.
A cholangiocarcinoma that is not amenable to surgical resection.
A cholangiocarcinoma that has recurred after a period of remission.
A cholangiocarcinoma that is amenable to surgical resection.
A transitional cell carcinoma that arises from the male or female urethra.
A rare adenocarcinoma that arises from the rete testis. It is usually manifested with a scrotal mass or lumbar pain.
A sex cord-stromal tumor that arises from the testis and is characterized by the presence of cells that resemble the successive stages of development of Leydig cells. It usually presents as a painless testicular mass. Gynecomastia is present in approximately thirty percent of the cases. Libido may be decreased. In children, precocious puberty may be present. A minority of cases exhibit malignant characteristics.
Ewing sarcoma which has not spread from its initial site.
A leukemia arising as a result of the mutagenic effect of chemotherapy agents that are used for the treatment of a malignant tumor.
A syndrome characterized by abnormal secretion of chorionic gonadotropin in conjunction with neoplastic growth occurring anywhere in the body.
Stage I includes: IA: (T1, N0, M0) and IB: (T1, N1, M0); (Ta/b, N0, M0). T1: Tumor invades lamina propria or submucosa. T2: Tumor invades the muscularis propria or the subserosa. T2a: Tumor invades muscularis propria. T2b: Tumor invades subserosa. N0: No regional lymph node metastasis. N1: Metastasis in 1 to 6 regional lymph nodes. N2: Metastasis in 7 to 15 regional lymph nodes. M0: No distant metastasis. (AJCC 6th ed.)
Stage III includes: IIIA (T2a/b, N2, M0); (T3, N1, M0); (T4, N0, M0). IIIB: (T3, N2, M0). N0: No regional lymph node metastasis. N1: Metastasis in 1 to 6 regional lymph nodes. N2: Metastasis in 7 to 15 regional lymph nodes. T2a: Tumor invades muscularis propria. T2b: Tumor invades subserosa. T3: Tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structures. T4: Tumor invades adjacent structures. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage II includes: (T1, N2, M0), (T2a/b, N1, M0), (T3, N0, M0). T1: Tumor invades lamina propria or submucosa. T2: Tumor invades muscularis propria or submucosa. T2a: Tumor invades muscularis propria. T2b: Tumor invades subserosa. T3: Tumor penetrates serosa (visceral peritoneum) without invasion of adjacent structures. N1: Metastasis in 1 to 6 regional lymph nodes. Metastasis in 7 to 15 regional lymph nodes. M0: No distant metastasis. (AJCC 6th ed.)
Stage IV includes: (T4, N1-3, M0); (T1-3, N3, M0); (Any T, Any N, M1). M1:Distant metastasis. (AJCC 6th ed.) - 2003
A hepatocellular carcinoma that is amenable to surgical resection.
Stage I bladder carcinoma associated with the presence of bladder carcinoma in situ.
A primary or metastatic malignant neoplasm that affects the uterine ligament.
A non-metastasizing neoplasm that arises from the uterine ligament.
The development of male secondary sexual characteristics (such as hirsutism, deepening of the voice, or clitoral enlargement) in girls or adult females.
Diffuse replacement of the lung tissue by connective tissue.
A renal functional disorder characterized by proteinuria, edema, hyperlipidemia and hypoalbuminemia. It results from damage to the renal vascular filtration apparatus. It is further characterized by scarring of some of the glomerular capillaries. Sequelae may include hypertension, atherosclerosis, infection, hypercoagulablity and renal failure.
A renal functional disorder characterized by proteinuria, edema, hyperlipidemia and hypoalbuminemia. It results from damage to the renal vascular filtration apparatus. It is further characterized by an inflammatory reaction in the filtering capillaries and the deposition of plasma components between the endothelium and glomerular basement membrane. Sequelae may include hypertension, atherosclerosis, infection, hypercoagulablity and renal failure.
A renal functional disorder characterized by proteinuria, edema, hyperlipidemia and hypoalbuminemia. It results from damage to the renal vascular filtration apparatus. It is further characterized by an inflammatory reaction in the endovascular lining of the glomerular capillaries. Sequelae may include hypertension, atherosclerosis, infection, hypercoagulablity and renal failure.
Nephrotic syndrome caused by glomerulonephritis associated with complement deficiency. It can result from an acute post-infectious glomerulonephritis, membranoproliferative glomerulonephritis or lupus glomerulonephritis.
A renal functional disorder characterized by proteinuria, edema, hyperlipidemia and hypoalbuminemia. It results from damage to the renal vascular filtration apparatus. It is further characterized by a chronic inflammatory reaction in the glomerular capillaries. Sequelae may include hypertension, atherosclerosis, infection, hypercoagulablity and renal failure.
A syndrome of immunologically mediated tissue damage that may occur following an allogeneic transplant, and may affect multiple organs with manifestations similar to autoimmune diseases. The onset is usually within three years of transplantation or immunologic manipulation.
A wide group of related learning disorders characterized by difficulties with mathematics and manipulating numbers; the difficulty with math may be caused or exacerbated by visuo-spatial or language processing difficulties.
Hyperkeratosis is thickening of the outer layer of the skin, the stratum corneum, which is composed of large, polyhedral, plate-like envelopes filled with keratin which are the dead cells that have migrated up from the stratum granulosum.
The continuous sequential physiological and psychological changes during ADOLESCENCE, approximately between the age of 13 and 18.
A mental illness that persists for a prolonged period of time. Use a more specific term if possible.
A period in which the infection is present in the host without producing overt symptoms. (from Online Medical Dictionary)
Temporary, non-covalent binding between protein molecules. Protein-protein interactions occur as a result of intermolecular physical forces and spatial complementation between domains or motifs. This interaction can be either homotypic or heterotypic and effect protein structure, conformation, and function.
Progressive decline in muscle mass due to aging which results in decreased functional capacity of muscles.
A DNA Strand Break involves one or more disruptions of the covalent linkages among phosphodeoxyribose moieties within the sugar-phosphate backbone in one or in both strands of a DNA molecule.
An impairment that causes an individual to require assistance in order to perform an activity.
An extremely rare autosomal recessively inherited neuromuscular disease characterised by ocular manifestations such as ptosis and diplopia followed by chronic diarrhoea, malnutrition and intestinal pseudo-obstruction.
A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Infectious diseases that are novel in their outbreak ranges (geographic and host) or transmission mode.
The round, black berries of the flowering shrub Vitex agnus-castus, native to Mediterranean countries and Asia. Chaste berries contain glycosides, flavonoids, alkaloids, monoterpenes, and sesquiterpenes. Chaste berries are considered as a reproductive tonic herb.
The acetate salt form of ganirelix, a synthetic decapeptide with high antagonistic activity against naturally occurring gonadotropin-releasing hormone (GnRH). Ganirelix directly competes with the GnRH for receptor binding in the anterior pituitary gland, thus induces a rapid and reversible suppression of the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH). This agent is used for the inhibition of premature LH surges in women undergoing controlled ovarian hyperstimulation, and in combination with other hormones for retrieval of the mature follicles for in-vitro fertilization.
The phosphate salt of oseltamivir, a synthetic derivative prodrug of ethyl ester with antiviral activity. By blocking neuraminidases on the surfaces of influenza viruses, oseltamivir interferes with host cell release of complete viral particles.
A 527 amino acid glycoprotein and the modified form of the naturally occurring human plasminogen activator (tPA) with tissue plasminogen activating activity. Tenecteplase (TNKase) is a serine protease created by introducing substitutions of threonine 103 with asparagine, asparagine 117 with glutamine within the kringle 1 domain, and a tetra-alanine substitution at amino acids 296-299 in the protease domain. TNKase converts fibrin-bound plasminogen to plasmin by cleaving the Arg/Val bond in plasminogen. Plasmin in turn degrades the fibrin matrix of the thrombus mass, thereby helps eliminate blood clots or arterial blockages that cause myocardial infarction.
The potassium salt form of pemirolast, a pyrimidinone derivative with antiallergic property. Pemirolast potassium exerts its action by blocking the antigen-mediated calcium ion influx into mast cells. This prevents mast cell degranulation, resulting in mast cell stabilization and inhibition of the release of inflammatory mediators, histamine and leukotrienes, which are involved in the allergic process. Pemirolast potassium also prevents inflammatory mediator release from eosinophils.
The hydrochloride salt of an orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity. Pioglitazone activates peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, thereby inducing cell differentiation and inhibiting cell growth and angiogenesis. This agent also modulates the transcription of insulin-responsive genes, inhibits macrophage and monocyte activation, and stimulates adipocyte differentiation. (NCI05)
The hydrochloride salt of imidapril, an angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, imidapril is converted by hydrolysis in the liver into its active form imidaprilat. Imidaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Imidaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
The orally bioavailable, hydrochloride salt form of berberine, a quaternary ammonium salt of an isoquinoline alkaloid and active component of various Chinese herbs, with potential antineoplastic, radiosensitizing, anti-inflammatory, anti-lipidemic and antidiabetic activities. Although the mechanisms of action through which berberine exerts its effects are not yet fully elucidated, upon administration this agent appears to suppress the activation of various proteins and/or modulate the expression of a variety of genes involved in tumorigenesis and inflammation, including, but not limited to transcription factor nuclear factor-kappa B (NF-kB), myeloid cell leukemia 1 (Mcl-1), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), cyclooxygenase (COX)-2, tumor necrosis factor (TNF), interleukin (IL)-6, IL-12, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 2 (CXCL2), cyclin D1, activator protein (AP-1), hypoxia-inducible factor 1 (HIF-1), signal transducer and activator of transcription 3 (STAT3), peroxisome proliferator-activated receptor (PPAR), arylamine N-acetyltransferase (NAT), and DNA topoisomerase I and II. The modulation of gene expression may induce cell cycle arrest and apoptosis, and inhibit cancer cell proliferation. In addition, berberine modulates lipid and glucose metabolism.
The dihydrate form of ceftibuten, a semisynthetic, beta-lactamase-stable, third-generation cephalosporin with antibacterial activity. Ceftibuten binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
An oligosaccharide composed of fructose units.
A standardized extract derived from the plant Boswellia serrata of the family Burseraceae with anti-inflammatory activity. Boswellia serrata extract contains terpenoid boswellic acids, which are potent inhibitors of 5-lipoxygenase activity and, so, leukotriene synthesis.
The aromatic root of perennial herbs of Panax ginseng.
S-enantiomer of bupivacaine that is used as a local anesthetic and for regional nerve blocks, including EPIDURAL ANESTHESIA.
The hydrochloride salt of levobupivacaine, an amide derivative with anesthetic property. Levobupivacaine reversibly binds voltage-gated sodium channels to modulate ionic flux and prevent the initiation and transmission of nerve impulses (stabilizing neuronal membrane), thereby resulting in analgesia and anesthesia. In comparison with racemic bupivacaine, levobupivacaine is associated with less vasodilation and has a longer duration of action.
The aromatic root of perennial herbs of Panax ginseng. Ginseng, used in traditional Chinese medicine and available as a nutritional supplement, is classified as an adaptogenic herb with multiple effects, many of them are regulatory in nature. It contains a complex mixture of saponins, ginsenosides and panaxosides. Although the mechanism of action is unclear, ginseng is reported to enhance the immune system and reduce fatigue.
The calcium salt of zofenopril, a sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, zofenopril is hydrolyzed in vivo into its active form zofenoprilat. Zofenoprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Zofenoprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A sulphonamide-derivative with thiazide-like diuretic activity. Meticrane acts in a similar manner as the thiazide diuretics.
The hydrochloride salt form of clorprenaline, a beta-2 adrenergic agonist with bronchodilator activity. Clorprenaline selectively binds to and activates beta-2 adrenergic receptors in bronchiolar smooth muscle, thereby causing stimulation of adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased intracellular cAMP levels cause relaxation of bronchial smooth muscle. This increases air flow and prevents bronchospasms and may eventually lead to an improvement of airway function.
The monohydrate form of creatine similar or identical to endogenous creatine produced in the liver, kidneys, and pancreas. Creatine, in phosphate form, helps supply energy to muscle cells for contraction. After intense effort, when ATP deposits are depleted, creatine phosphate donates phosphate groups toward the fast synthesis of ATP. Dietary supplementation with creatine may improve muscle wasting associated with cancer and other chronic diseases.
A synthetic derivative prodrug of ethyl ester with antiviral activity. Osetamivir blocks neuraminidases on the surfaces of influenza viruses, interfering with host cell release of complete viral particles.
A form of the mineral iron that is used to treat anemia caused by low amounts of iron in the blood. Anemia is a condition in which the number of red blood cells is below normal. Ferrlecit is a type of hematinic and a dietary supplement.
The hydrochloride salt form of aminolevulinic acid, an aminoketone, used for local photosensitizing therapy. Aminolevulinic acid (ALA) is a metabolic pro-drug that is converted into the photosensitizer protoporphyrin IX (PpIX), which accumulates intracellularly. Upon exposure to light of appropriate wavelength (red, or blue), PpIX catalyzes oxygen to singlet oxygen, an intracellular toxin, which can further react to form superoxide and hydroxyl radicals. This leads to cellular cytotoxic effects.
The recombinant form of the endogenous polypeptide hormone Glucagon consisting of 29 amino acids responsible for the release of stored glucose, causing increased blood glucose levels. Clinical Use: Diagnostic Aid for Imaging Studies and Hypoglycemia.
The hydrochloride salt form of levobetaxolol, the S-isomer of the -selective beta-1 adrenergic receptor antagonist betaxolol with anti-glaucoma activity and devoid of intrinsic sympathomimetic activity. When applied topically in the eye, levobetaxolol reduces aqueous humor secretion and lowers the intraocular pressure (IOP).
a kind of nonsteroidal anti-inflammatory drugs
An acute or chronic infectious process affecting the lungs.
Phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.
Weakness in the supporting structures of the pelvic floor allowing the pelvic viscera to descend or one or more of the pelvic organs drop from their normal position. [PMID:21505577, Sanford:krageth]
Bilateral convulsive seizures are focal seizure with secondary bilateral motor phenomena, not primary generalized seizures.
Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by spondyloepiphyseal dysplasia (SED) resulting in short stature, nephropathy, and T-cell deficiency. Radiographic manifestations of SED include ovoid and mildly flattened vertebral bodies, small deformed capital femoral epiphyses, and shallow dysplastic acetabular fossae. Adult height is 136-157 cm for men and 98.5-143 cm for women. Nearly all affected individuals have progressive steroid-resistant nephropathy, usually developing within five years of the diagnosis of growth failure and terminating with end-stage renal disease (ESRD). The majority of tested individuals have T-cell deficiency and an associated risk for opportunistic infection, a common cause of death. SIOD involves a spectrum that ranges from an infantile or severe early-onset form with death early in life to a juvenile or milder later-onset form with survival into adulthood if renal disease is appropriately treated.
An electrocardiographic finding of a lack of progression of R wave height across precordial leads. (CDISC)
An infectious process affecting a tooth.
A widespread acute rash characterized by fever and multiple small pustules on a reddish background.
Small areas of bleeding (hemorrhage) under the fingernail or toenail.
Inflammation of stomach that is associated with cytomegalovirus.
Inflammation of the esophagus that is associated with cytomegalovirus.
A non-neoplastic or neoplastic disorder arising as a result of the immunologic defects caused by Autoimmune Deficiency Syndrome.
A syndrome characterized by retropatellar or peripatellar PAIN resulting from physical and biochemical changes in the patellofemoral joint. The pain is most prominent when ascending or descending stairs, squatting, or sitting with flexed knees. There is a lack of consensus on the etiology and treatment. The syndrome is often confused with (or accompanied by) CHONDROMALACIA PATELLAE, the latter describing a pathological condition of the CARTILAGE and not a syndrome.
A variant of phlegmonous gastritis, typically progressing to gastric gangrene.
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Any deviation from the normal ratio of the volume of red blood cells to the total volume of blood. []
A collection of blood into the space between the dura mater and the skull.
The development of secondary female sex characteristics in males due to extrinsic factors.
A respiratory tract infection caused by a virus. Viruses represent the most common causes of upper and lower respiratory tract infections and include rhinoviruses, influenza viruses, parainfluenza viruses, and respiratory syncytial virus.
Ay severe form of gait ataxia such that an affected person cannot walk at all.
A finding of blood leakage from the intestinal stoma.
A laboratory finding indicating the presence of lower than normal bone mineral density.
A increased concentration of serotonin in the blood.
Any unfavorable or unintended disease, sign, or symptom (including an abnormal laboratory finding) that is temporally associated with the use of a medical treatment or procedure, and that may or may not be considered related to the medical treatment or procedure. Such events can be related to the intervention, dose, route of administration, patient, or caused by an interaction with another drug(s) or procedure(s).
A malignant neoplasm that has spread to the placenta from another anatomic site.
Pain experienced after a medical intervention through the time expected for associated acute effects to abate.
Ischemic necrosis of the bone tissue and the marrow.
A carcinoma that arises from the gallbladder and it has not spread to other anatomic sites.
The reemergence of gallbladder carcinoma after a period of remission.
An anatomic abnormality of the thyroid gland.
A malignant neoplasm that has spread to other anatomic sites or is no longer responding to treatment.
A hemangioma arising from the cerebral hemisphere.
A form of invasive candidiasis where species of CANDIDA are present in the blood.
A skin disease marked by scaly or thickened patches on the skin, and often caused by prolonged exposure to arsenic. The patches often occur on sunexposed areas of the skin and in older white men. These patches may become malignant (cancerous).
A non-congenital condition in which the head circumference is two standard deviations greater than the mean. Causes include infection, intraventricular hemorrhage, subdural hematoma, and arachnoid cysts.
Increased pigmentation, either focal or generalized, of the mucosa of the mouth.
Accumulation of fluid in the peritoneal cavity resulting from the growth of primary or metastatic carcinoma in the peritoneum.
A benign neoplasm of the ovary characterized by the presence of cystic structures lined by serous epithelial cells in a fibrotic stroma.
The development of a malignant neoplasm in response to medical or surgical treatment, induced by the treatment itself.
An aggressive malignant tumor of melanocytic origin that arises from the cervix.
A sleep disorder characterized by persistent sleep disruption (excessive sleepiness and/or insomnia) that is due to a conflict between the individual's internal sleep-wake system and the demands of his or her environment regarding the timing and duration of sleep.
The hydrochloride salt of a cytarabine congener prodrug with antineoplastic activity. Upon administration, ancitabine is slowly hydrolyzed into cytarabine. Subsequently, cytarabine is converted to the triphosphate form within the cell and then competes with cytidine for incorporation into DNA. Because the arabinose sugar sterically hinders the rotation of the molecule within DNA, DNA replication ceases, specifically during the S phase of the cell cycle. Cytarabine agent also inhibits DNA polymerase, resulting in a decrease in DNA replication and repair. Compared to cytarabine, a more prolonged, consistent cytarabine-mediated therapeutic effect may be achieved with ancitabine because of the slow hydrolytic conversion of ancitabine to cytarabine.
The maleate salt form of quipazine, a piperazine-based nonselective serotonin (5-HT) receptor agonist with antidepressant and oxytocic activities. Quipazine targets and binds to serotonin receptors, particularly to the 5HT2A and 5HT3 receptors. Serotonin receptor activation by quipazine may lead to smooth muscle contraction and antidepressant effects.
A primitive neuroectodermal tumor (small round blue cell tumor) of the thorax which can involve the periosteum, thoracic wall and/or pleura though it spares the lung parenchyma.
Embolism or thrombosis occurring in a cerebral vessel often leading to cerebral infarction.
A leukemia characterized by the absence of leukemic cells in the peripheral blood.
The sodium salt form of Brequinar. Brequinar inhibits the enzyme dihydroorotate dehydrogenase, thereby blocking de novo pyrimidine biosynthesis. This agent may also enhance the in vivo antitumor effect of antineoplastic agents such as 5-FU. (NCI04)
A dioxolane derivative and a novel L-configuration deoxycytidine analogue with potent antineoplastic activity. When incorporated into growing chain during DNA replication, troxacitabine stops DNA polymerization due to its unnatural L-configuration, in contrast to the normal nucleotides with D-configuration. As a result, this agent terminates DNA synthesis upon incorporated into DNA molecules, and consequently interrupts tumor cell proliferation.
An immunoconjugate of the monoclonal antibody ibritumomab conjugated with the linker-chelator tiuxetan, a high affinity, conformationally restricted chelation site for radioisotopes. When bound to indium In 111 or yttrium Y 90, ibritumomab tiuxetan, targeting the CD20 antigen on B cell surfaces, specifically delivers a potentially cytotoxic dose of radiation to B lymphocytes. Ibritumomab is a murine IgG1 kappa monoclonal antibody directed against the CD20 antigen, which is found on the surface of normal and malignant B lymphocytes.
Tradename for beta-Aminoethylisothiuronium Bromide
Originally, the name laetrile was the contraction of laevo-mandelonitrile glucoside, a cyanogenic glycoside found naturally in some plants. Over the years the meaning of laetrile has changed. There are now preparations called Laetrile where amygdalin is the major constituent. Laetrile and amygdalin are often used interchangeably, but are different agents. Cyanide and benzaldehyde are metabolites of both laetrile and amygdalin. Both metabolites may possess antineoplastic properties. Laetrile has been used as an anticancer treatment in humans worldwide, but scientific evidence does not support its effectiveness. It is not approved for use in the United States. (NCI04)
The thickening of the wall of the small arteries and arterioles. It is caused by deposition of hyaline material in the wall or concentric smooth muscle wall hypertrophy. It results in lumen narrowing and tissue ischemia.
A precancerous neoplastic process that affects the squamous, glandular, or transitional cell epithelium without evidence of invasion. According to the degree of nuclear atypia, number of mitotic figures, and presence of architectural distortion, it is classified as low grade (mild dysplasia) or high grade (moderate or severe dysplasia).
A neuroblastoma arising from the peripheral nervous system.
A disease of the heart muscle or myocardium proper. Cardiomyopathies may be classified as either primary or secondary, on the basis of etiology, or on the pathophysiology of the lesion: hypertrophic, dilated, or restrictive.
Diffuse panbronchiolitis (DPB) is a rare chronic inflammatory obstructive pulmonary disease primarily affecting the respiratory bronchioles. 'Diffuse' refers to the distribution of the lesions throughout both lungs, and 'pan-' refers to the involvement of inflammation in all layers of the respiratory bronchioles. Onset of the disorder occurs in the second to fifth decade of life, and is clinically manifest by chronic cough, exertional dyspnea, and sputum production. Most patients also have chronic paranasal sinusitis. If untreated, the disorder progresses to bronchiectasis, respiratory failure, and death (summary by Poletti et al., 2006).
A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
A condition that is characterized by HEADACHE; SEIZURES; and visual loss with edema in the posterior aspects of the CEREBRAL HEMISPHERES, such as the BRAIN STEM. Generally, lesions involve the white matter (nerve fibers) but occasionally the grey matter (nerve cell bodies).
Also known as shaky legs syndrome, this is a rare movement disorder with characteristics of fast, task-specific tremor, affecting the legs and trunk while standing. The prevalence is unknown. To date, around 390 cases have been reported in the literature. Women are predominantly affected (sex ratio: 2:1) with disease onset occurring in middle aged or elderly people. At present, the pathophysiology is unknown. The disorder is sporadic but exceptional familial cases have been reported.
Metastatic lesion of the UMBILICUS associated with intra-abdominal neoplasms especially of the GASTROINTESTINAL TRACT or OVARY.
Reduced motility through the sphincter of Oddi, resulting in impedance of bile and pancreatic juice flow from the common bile duct into the duodenum.
An abnormal increase or decrease of weight or an abnormal distribution of mass in the body.
A non-neoplastic polyp that arises from the stomach and is characterized by the presence of dilated gastric foveoli, edematous changes, and inflammation.
A skin change elicited by briskly rubbing the skin lesion in urticaria pigmentosa (UP), whereby the area begins to itch and becomes raised and surrounded by erythema. Unlike other forms of dermatographism, Darier's sign refers to urtication that is limited to the UP involved areas and, as in this case, spares the skin unaffected by UP.
A kind of short stature in which different regions of the body are shortened to differing extents.
A kind of short stature in which different regions of the body are shortened to a comparable extent.
Analbuminemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. Affected individuals have few clinical symptoms other than mild edema, hypotension, fatigue, and, occasionally, a peculiar lower body lipodystrophy (mainly in adult females). The most common biochemical finding is a gross hyperlipidemia, with a significant increase in the total and LDL cholesterol concentrations, but normal concentrations of HDL cholesterol and triglycerides. Analbuminemia often leads to fetal or neonatal death in sibs in families of analbuminemic subjects, which may explain the rarity of the trait (summary by Caridi et al., 2014).
Elevanted concentration of urate in the urine.
A rare form of non-Langerhans-cell histiocytosis (HISTIOCYTOSIS, NON-LANGERHANS-CELL) with onset in middle age. The systemic disease is characterized by infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones.
Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase (PAH; 612349), tyrosine hydroxylase (TH; 191290) and tryptophan hydroxylase (TPH1; 191060), the latter 2 of which are involved in neurotransmitter synthesis. The BH4-deficient HPAs are characterized phenotypically by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits (Dudesek et al., 2001). HPABH4A, caused by mutations in the PTS gene, represents the most common cause of BH4-deficient hyperphenylalaninemia (Dudesek et al., 2001). Other forms of BH4-deficient HPA include HPABH4B (233910), caused by mutation in the GCH1 gene (600225), HPABH4C (261630), caused by mutation in the QDPR gene (612676), and HPABH4D (264070), caused by mutation in the PCBD1 gene (126090). Niederwieser et al. (1982) noted that about 1 to 3% of patients with hyperphenylalaninemia have one of these BH4-deficient forms. These disorders are clinically and genetically distinct from classic phenylketonuria (PKU; 261600), caused by mutation in the PAH gene. Two additional disorders associated with BH4 deficiency and neurologic symptoms do not have overt hyperphenylalaninemia as a feature: dopa-responsive dystonia (612716), caused by mutation in the SPR gene (182125), and autosomal dominant dopa-responsive dystonia (DYT5; 128230), caused by mutation in the GCH1 gene. Patients with these disorders may develop hyperphenylalaninemia when stressed.
Danon disease is an X-linked dominant disorder predominantly affecting cardiac muscle. Skeletal muscle involvement and mental retardation are variable features. The accumulation of glycogen in muscle and lysosomes originally led to the classification of Danon disease as a variant of glycogen storage disease II (Pompe disease; 232300) with 'normal acid maltase' or alpha-glucosidase (GAA; 606800) (Danon et al., 1981). However, Nishino et al. (2000) stated that Danon disease is not a glycogen storage disease because glycogen is not always increased. Sugie et al. (2005) classified Danon disease as a form of autophagic vacuolar myopathy, characterized by intracytoplasmic autophagic vacuoles with sarcolemmal features. The characteristic vacuole is believed to be an autolysosome surrounded by secondarily-generated membranes containing sarcolemmal proteins, basal lamina, and acetylcholinesterase activity. X-linked myopathy with excessive autophagy (XMEA; 310440) is a distinct disorder with similar pathologic features.
Dent disease, an X-linked disorder of proximal renal tubular dysfunction, is characterized by low molecular-weight (LMW) proteinuria, hypercalciuria, and at least one additional finding including nephrocalcinosis, nephrolithiasis, hematuria, hypophosphatemia, chronic kidney disease (CKD), and evidence of X-linked inheritance. Males younger than age ten years may manifest only LMW proteinuria and/or hypercalciuria, which are usually asymptomatic. Thirty to 80% of affected males develop end-stage renal disease (ESRD) between ages 30 and 50 years; in some instances ESRD does not develop until the sixth decade of life or later. The disease may also be accompanied by rickets or osteomalacia, growth restriction, and short stature. Disease severity can vary within the same family. Males with Dent disease 2 (caused by pathogenic variants in OCRL) may also have mild intellectual disability, cataracts, and/or elevated muscle enzymes. Due to random X-chromosome inactivation, some female carriers may manifest hypercalciuria and, rarely, renal calculi and moderate LMW proteinuria. Females rarely develop CKD.
Aceruloplasminemia is characterized by iron accumulation in the brain and viscera. The clinical triad of retinal degeneration, diabetes mellitus (DM), and neurologic disease is seen in individuals ranging from age 30 years to older than 70 years. The neurologic findings of movement disorder (blepharospasm, grimacing, facial and neck dystonia, tremors, chorea) and ataxia (gait ataxia, dysarthria) correspond to regions of iron deposition in the brain. Individuals with aceruloplasminemia often present with anemia prior to onset of DM or obvious neurologic problems. Cognitive dysfunction including apathy and forgetfulness occurs in more than half of individuals with this condition.
PROP1-related combined pituitary hormone deficiency (CPHD) is associated with deficiencies of growth hormone (GH); thyroid-stimulating hormone (TSH); the two gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH); prolactin (PrL); and occasionally adrenocorticotropic hormone (ACTH). Most affected individuals are ascertained because of growth failure and failure to thrive starting in infancy or early childhood (approximate age range: 9 months to 8 years). Hypothyroidism is usually mild and occurs in later infancy and childhood. Affected individuals can have absent or delayed and incomplete secondary sexual development with infertility. Untreated males usually have a small penis and small testes. Some females experience menarche, but subsequently require hormone replacement therapy. ACTH deficiency is less common and, when present, usually occurs in adolescence or adulthood.
SHORT syndrome is a mnemonic for short stature, hyperextensibility, ocular depression (deeply set eyes), Rieger anomaly, and teething delay. It is now recognized that the features most consistently observed in SHORT syndrome are mild intrauterine growth restriction (IUGR); mild short stature; partial lipodystrophy (evident at birth in the face, and later in the chest and upper extremities, often sparing the buttocks and legs); and a characteristic facial gestalt. Other frequent features include: Axenfeld-Rieger anomaly or related ocular anterior chamber dysgenesis; delayed dentition and a variety of dental abnormalities; insulin resistance (typically in mid-childhood to adolescence) and/or diabetes mellitus in early adulthood; and sensorineural hearing loss. To date the diagnosis has been molecularly confirmed in individuals from 16 families; thus, the current understanding of the phenotypic spectrum and natural history are likely to evolve over time.
Symptom of overactive detrusor muscle of the URINARY BLADDER that contracts with abnormally high frequency and urgency. Overactive bladder is characterized by the frequent feeling of needing to urinate during the day, during the night, or both. URINARY INCONTINENCE may or may not be present.
Less than normal linear growth in an infant or child.
A cancer vaccine comprised of peptides derived from the extracellular domain of the tumor-associated antigen Her-2/neu with potential antineoplastic activity. HER-2/neu peptide vaccine may induce antibodies with anti-tumor activity and may also elicit a specific CD8 T-cell response against specific tumor cell types. (NCI04)
A radioimmunotherapeutic monoclonal antibody (MN-14) directed against tumor-associated carcinoembryonic antigen (CEA) and chelated to the radioisotope yttrium-90 (Y 90). Yttrium 90 monoclonal antibody MN-14 binds to tumor cell expressing CEA, delivering a cytotoxic dose of beta radiation. (NCI04)
A radioimmunoconjugate of a murine monoclonal antibody, MoAb MN-14, labeled with indium 111 (In-111). MoAb Lym-1 recognizes an epitope of carcinoembryonic antigen (CEA), which is over-expressed in many tumor cell types. In-111 MoAb MN-14 emits gamma radiation and X-Ray photons that can be captured by gamma camera allowing imaging of tumor cells that express CEA.
A familial carcinoma inherited in an autosomal dominant trait. It is characterized by the development of multiple, bilateral papillary renal cell carcinomas. The carcinomas range from microscopic lesions to clinically symptomatic tumors. It is associated with activating mutations of the MET oncogene.
An oral fluoropyrimidine antagonist composed of tegafur combined with two modulators of 5-flurouracil (5-FU) activity, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate, in a molar ratio of 1:0.4:1. Tegafur is a prodrug of 5-fluorouracil, an antimetabolite that inhibits thymidylate synthase, thereby inhibiting DNA synthesis and cell division, and competes with uridine triphosphate, thus inhibiting RNA and protein synthesis. CDHP is a reversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. Potassium oxonate preferentially localizes in the gut and inhibits the enzyme orotate phosphoribosyltransferase (the major enzyme responsible for 5-FU activation), thereby decreasing activation of 5-FU in the gut and activated 5-FU-related gastrointestinal toxicity. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43548&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43548&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1833"" NCI Thesaurus)
An autologous dendritic cells vaccine with antineoplastic property. Dendritic cells harvested from cancer patients are pulsed with human gp100 melanoma antigen and MART-1 (melanoma antigen recognized by T-cells) antigen; both antigens are up-regulated in melanomas. Vaccination with this vaccine may elicit the host immune response against MART-1 or gp100 expressing cells.
A therapeutic agent produced by isolating tumor cells from an individual and processing these tumor cells into a vaccine formulation in vitro; the vaccine is then administered to the individual from whom the tumor cells were isolated. Typically combined with an adjuvant immunostimulant, an autologous cell vaccine may elicit a cytotoxic T-lymphocytic immune response to cell surface-expressed tumor-associated antigens (TAAs), resulting in tumor cell death. (NCI04)
A proprietary vaccine adjuvant consisting of an oil-in-water emulsion of saponin QS21 and monophosphoryl lipid A with potential immunostimulating activity. Mono-phosphoryl lipid A is a detoxified derivative of lipid A, a component of lipopolysaccharide (LPS) found in most gram-negative bacteria. QS21 is a purified saponin fraction extracted from the South American tree Quillaja saponaria Molina. When co-administered with peptide vaccines, the adjuvant vaccine may elicit strong humoral and cellular immune responses.
An iodine 131 labeled radioimmunoconjugate of monoclonal antibody (MOAB) TNT-1/B with radioimaging and antineoplastic properties. MOAB TNT-1/B was developed for radioimmunotherapy of solid tumors, designated as Tumor Necrosis Treatment (TNT). TNT exploits the presence of degenerating and necrotic cells within tumors by utilizing MOAbs directed against universal, intracellular nucleosomal determinants consisting of histone H1 and DNA. This MOAB was conjugated with biotin (B) molecules, which increase pharmacokinetic performance of the monoclonal antibody. MOAB TNT-1/B delivers I 131 to tumor cells and results in the targeted imaging and/or destruction of cells with exposed necrotic antigens.
A pyridyl cyanoguanidine that exhibits antitumor activity by an unknown mechanism. (NCI)
A pyrimido-pyrimidine with antitumor activity. BIBX 1382 inhibits the intracellular tyrosine kinase domain of the Epidermal Growth Factor Receptor (EGFR) thus specifically reversing the aberrant enzymatic activity from overexpressed and constitutively activated EGFR, and subsequently inhibiting cell proliferation and inducing cell differentiation.
A cancer vaccine consisting of autologous dendritic cells which have been pulsed with a mutant p53 peptide. Vaccination with mutant p53 peptide pulsed dendritic cells may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing mutant p53, resulting in tumor cell lysis. Many tumor cells overexpress mutant p53 proteins, resulting in the loss of apoptosis regulation and abnormal cell proliferation. (NCI04)
A multivalent antineoplastic vaccine comprised of the bcr-abl oncogene breakpoint fusion peptide that elicits a bcr-abl specific T-cell immune response. (NCI04)
A synthetic peptide vaccine consisting of amino acids 86 through 93 (TLGIVCPI) of the viral oncoprotein human papillomavirus (HPV) 16 E7. Vaccination with HPV-16 E7:86-93 peptide, which binds to HLA-A* 0201 molecule, may stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells positive for HPV-16 E7.
A peptide-based cancer vaccine composed of amino acids 264 to 272 of the wild-type protein encoded by the P53 gene. p53 peptide vaccine may elicit an HLA-A2.1-restricted cytotoxic T lymphocyte immune response against tumor cells that overexpress p53 protein. (NCI04)
A radioimmunoconjugate of humanized monoclonal antibody (MoAb) HMFG1 labeled with Yttrium 90 (Y-90). MoAb MFG1 was raised against Human Milk Fat Globules and reacts with an epitope (PDTR) in the protein core of MUC1 mucins, which are up-regulated in human breast and other carcinomas.Y-90 MoAb HMFG1 delivers beta particle emitting Y-90 radionuclide directly to tumor cells that express MUC1, thereby this agent may be used in radioimmunotherapy of cancers.
A radioimmunotherapeutic humanized murine monoclonal antibody (LL2) directed against the CD22 pan-B-cell antigen and chelated to the radioisotope yttrium-90 (Y 90). Y 90 humanized monoclonal antibody LL2 binds to tumor cells expressing CD22, delivering a cytotoxic dose of beta radiation.
A recombinant vaccinia virus encoding the T-cell co-stimulatory molecule B7-1. Co-administration of recombinant vaccinia-B7.1 and a tumor-associated antigen vaccine may enhance tumor-associated antigen-specific T-cell responses. (NCI04)
A prodrug in which a peptide is covalently conjugated with the anthracycline antineoplastic antibiotic doxorubicin. This complex is hydrolyzed by the enzyme prostate-specific antigen (PSA), resulting in the formation of doxorubicin and leucine-doxorubicin. Selective targeting of these drugs to prostate tumor cells occurs because the hydrolyzing PSA enzyme is localized to the prostate gland. Doxorubicin and leucine-doxorubicin intercalate into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. These agents also produce toxic free-radical intermediates and interact with cell membrane lipids causing lipid peroxidation. (NCI04)
A synthetic oligodeoxynucleotide. Functioning as an anti-sense agent, it hybridizes to the translation initiation region of the human mRNA for the oncogene H-Ras. ISIS 2503 selectively inhibits the expression of H-Ras, and may inhibit the growth of some Ras-dependent tumor cells. (NCI04)
A humanized anti-idiotypic (anti-Id) monoclonal antibody (MoAb) that mimics the disialoganglioside GD2 with potential immunostimulating and antineoplastic activities. Upon administration, monoclonal antibody 4B5 anti-idiotype vaccine may elicit both cellular and humoral immune responses against GD2- expressing tumor cells. GD2 is a glycosphingolipid (ceramide and oligosaccharide) that may be highly expressed by melanomas and other neuroectodermal tumors, while only minimally expressed by normal tissues.
An autologous dendritic cell vaccine with potential immunostimulatory activity. Dendritic cells harvested from a prostate cancer patient are transfected with the mRNA encoding for prostate specific antigen (PSA), a tumor marker secreted by prostatic epithelial and ductal cells. When reintroduced back to the patient, these PSA RNA pulsed autologous dendritic cells may elicit a cytotoxic T-cell (CTL) response against PSA-positive prostate cancer cells.
A murine IgG2 monoclonal antibody directed against the CD20 antigen, found on the surface of B-cells. Tositumomab binds to the CD20 surface membrane antigen, resulting in apoptosis, and may stimulate antitumoral cell-mediated and/or antibody-dependent cytotoxicity. (NCI04)
An immunoconjugate comprised of an anti-CD19 monoclonal antibody conjugated with Genistein selectively targeting B-lineage progenitor cells and inhibiting protein tyrosine kinase, causing apoptosis.
A human monoclonal antibody produced in transgenic mice that attaches to the transmembrane epidermal growth factor (EGF) receptor. Panitumumab may inhibit autocrine EGF stimulation of tumor cells that express the EGF receptor, thereby inhibiting tumor cell proliferation.
A vitamin D3 analogue with potential antineoplastic activity. ILX23-7553 binds to and activates the vitamin D receptor, a cytoplasmic polypeptide expressed in normal vitamin D responsive tissues, but also overexpressed in certain cancers including hepatocellular carcinoma and pancreatic cancer. Mediated through vitamin D receptor, this agent induces cancer cell differentiation, inhibits cancer cell growth and induces apoptosis. In addition, ILX23-7553 may also induce growth arrest and apoptosis independent of vitamin D receptor activation through mechanisms that are not fully elucidated.
A cell that is antigenically distinct from other lymphocytes.
A cancer vaccine containing PR1, a 9 amino-acid human leukocyte antigen (HLA)-A2 restricted peptide derived from proteinase 3, with potential immunotherapeutic activity. Vaccination with PR1 leukemia peptide vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing proteinase 3, resulting in tumor cell lysis. Often overexpressed in leukemic cells, proteinase 3 is a serine proteinase that activates progelatinase A and is involved in angiogenesis and metastasis.
An anthranilamide derivative with multidrug resistance properties. Tariquidar non-competitively binds to the p-glycoprotein transporter, thereby inhibiting transmembrane transport of anticancer drugs. Inhibition of transmembrane transport may result in increased intracellular concentrations of an anticancer drug, thereby augmenting its cytotoxicity. (NCI04)
An agent binding to the leukotriene B4 receptor, leading to reduced interleukin-2 mediated hypoxia. Biomed 101 does not affect interleukin-2 antitumor activity. (NCI04)
ILX-295501 is a novel sulfonylurea compound that has demonstrated in-vivo antitumor activity against a broad spectrum of solid tumors.
A 19 amino-acid hybrid peptide antigen with immune adjuvant property. OVA-BiP peptide consists of 8 amino acids from ovalbumin joined via a tripeptide linker to a stretch of 8 amino acids, the minimum binding domain of BiP (immunoglobulin heavy chain-binding protein, aka grp78), a member of the heat shock protein (hsp) 70 family. As a chaperon, BiP binds to newly synthesized, unfolded mu immnoglobulin heavy chains prior to its assembly with light chains in the endoplasmic reticulum. In conjunction with a tumor antigen, this hybrid peptide is used to potentiate antigen presentation and consequently prime cytotoxic T lymphocyte responses.
An antibody with potential antineoplastic activity. Specific for both the high-affinity immunoglobulin G (IgG) receptor CD64 and epidermal growth factor receptor (EGFR), bispecific antibody MDX447 may enhance cellular immune responses against EGFR positive cells, resulting in increased tumor cell lysis. (NCI04)
A recombinant, chimeric, dual-receptor agonist fusion protein with immunohematopoietic activity. Progenipoietin (ProGP) consists of portions of the ligands for granulocyte colony-stimulating factor (G-CSF) and human fetal liver tyrosine kinase-3 (FLT3); variants progenipoietin-1, 2 and 3 differ in the orientation of the two receptor agonists. ProGP binds simultaneously to G-CSF and FLT3 receptors with receptor affinities approximately two- to three-fold higher than the respective native ligands. When administered in vivo, this agent may augment the number of circulating granulocytes and dendritic cells (DCs). ProGP may promote the proliferation of and prevent apoptosis in several human hematopoietic cell lineages, exhibiting the additive activities of a combination of C-GSF and FLT3.
A peptide vaccine consisting of the whole or partial beta subunit of human chorionic gonadotrophin hormone (hCG), linked to an adjuvant carrier of bacterial or viral origin, with anti-fertility activity. Anti-human chorionic gonadotropin vaccine blocks the activity of hCG which is naturally produced by the trophectoderm of the pre-implantation embryo within a few days of fertilization. hCG is required for the maintenance of the corpus luteum in the ovary thus ensuring its continued production of progesterone, which is required for the successful completion of implantation of the blastocyst. Without progesterone, the corpus luteum regresses, and menstruation is initiated.
A humanized monoclonal antibody deficient in Fc receptor binding directed against CD3 on the surfaces of T cells. Monoclonal antibody HuM291 binds to the CD3 portion of the CD3:TCR (T-cell receptor) complex expressed on the surface of T cells, resulting in apoptosis of antigen-activated T cells., Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38004&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38004&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2229"" NCI Thesaurus)
A radioimmunoconjugate of humanized M195 monoclonal antibody (MoAb) conjugated with isotope yttrium 90. MoAb M195 is reactive with the cell surface antigen CD33, a glycoprotein found on myeloid leukemia blasts and early hematopoietic progenitor cells but not on normal stem cells. This radioimmunoconjugate emits beta particles that causes cytotoxicity in tumor cells and has both imaging and therapeutic uses.
A humanized monoclonal antibody directed against the Lewis Y antigen, a tumor-associated epithelial antigen, with potential antineoplastic activity. Following binding, monoclonal antibody Hu3S193 triggers an antibody-dependent cell-mediated cytotoxicity in cells expressing Lewis Y antigen. (NCI05)
A peptide vaccine, containing human tumor-associated epithelial mucin (MUC1) conjugated with keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. Vaccination with MUC1-KLH conjugate vaccine may stimulate humoral and cytotoxic T-lymphocyte (CTL) responses against tumor cells expressing the MUC1 antigen. In this vaccine, MUC1 antigen is conjugated with KLH, an immunostimulant and a hapten carrier, to enhance immune recognition. MUC1 antigen, a membrane-bound glycoprotein expressed by most glandular and ductal epithelial cells, is overexpressed in an aberrant or deglycosylated form in various cancers such as those of the breast, prostate, and ovary.
A cell-based vaccine composed of autologous antigen-presenting peripheral blood mononuclear cells (enriched for a dendritic cell fraction) that have been exposed to a recombinant protein consisting of granulocyte-macrophage colony-stimulating factor (GM-CSF) fused to prostatic-acid phosphatase (PAP), a protein expressed by prostate cancer cells. Upon administration, the vaccine may stimulate an antitumor T-cell response against tumor cells expressing PAP. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38038&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38038&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1985"" NCI Thesaurus)
A genetically-engineered protein formed by the fusion of prostatic acid phosphatase (PAP) and sargramostim (GM-CSF). Vaccination with antigen-presenting cells (APC) loaded with prostatic acid phosphatase-sargramostim fusion protein may elicit a cytotoxic T-cell response against tumor cells that express PAP. (NCI05)
A population of a type of antigen-presenting cell (APC), the dendritic cell (DC), harvested from a patient and grown in vitro in the presence of tumor-associated antigens (TAAs) derived from the patient's tumor (a technique known as 'pulsing') and then injected back into the patient; autologous DCs so manipulated may stimulate a specific cell-mediated antitumoral cytotoxicity. DCs derived from a patient may also be fused with the patient's tumor cells in vitro to combine sustained tumor antigen expression with the antigen-presenting and immunostimulatory capacities of DCs; when injected back into the patient, these autologous DC-tumor cell hybrids (fusion cells) may stimulate an active antitumoral immune response.
An analog of thalidomide with potential antineoplastic activity that belongs to the functional class of agents called selective cytokine inhibitory drugs (SelCIDs). SelCIDs inhibit phosphodiesterase-4 (PDE 4), an enzyme involved in tumor necrosis factor alpha (TNF alpha) production. CC-1088 inhibits production of the cytokines vascular endothelial growth factor (VEGF) (a pro-angiogenic factor) and interleukin-6 (IL-6). (NCI04)
A quinolinone derivative that inhibits farnesyl protein transferase, an enzyme that mediates the farnesylation of RAS, causing possible inhibition of the RAS pathway.
A radioimmunoconjugate of humanized monoclonal antibody (MoAb) 3S193 labelled with Indium 111 (In-111). MoAb Hu3S193 recognizes a Lewis Y carbohydrate antigen present on the surface of many carcinomas. This radioimmunoconjugate emits gamma radiation and X-ray photons, thereby allowing detection of tumor localization and distribution of MoAb HuS193 in diagnostic imaging procedures.
An inherited condition characterized by the development of kidney oncocytomas which are often bilateral and multifocal. This condition may be connected to Birt-Hogg-Dube syndrome.
A gene-viral vector complex comprised of an adenovirus vector and B7-1 gene targeting the CD80 antigen. Adenovirus B7-1 is used as a component in antineoplastic vaccines to elicit a cytotoxic T-cell response. (NCI04)
A benign or malignant mesenchymal neoplasm composed of stromal cells. Representative examples include gastrointestinal stromal tumor, endometrial stromal sarcoma, and prostate stromal sarcoma.
A radioimmunoconjugate of the humanized IgG1 monoclonal antibody (MoAb) LL2 (epratuzumab) labeled with indium 111 (In-111). MoAb LL2 recognizes CD22, a B-lymphocyte-restricted antigen expressed as a cytoplasmic protein in progenitor B cells, and as a cell surface protein in mature B cells. In-111 MoAb LL2 emits gamma radiation and X-Ray photons that can be captured by gamma camera allowing imaging of tumor cells that express CD22 antigen.
The term was used in various ways in the past, to describe unintended effects of medical intervention, usually negative (unfavourable), but also positive (favourable) ones. It is recommended that this term no longer be used and particularly should not be regarded as synonymous with adverse event or adverse reaction.
The morpholinoethyl ester of mycophenolic acid (MPA). As an immunosuppressive agent in vivo, the active metabolite mycophenolate reversibly inhibits inosine 5'-monophosphate dehydrogenase (IMPDH), an enzyme involved in the de novo synthesis of guanine nucleotides, thereby retarding T-cell and B-cell proliferation. MPA displays high lymphocyte specificity and cytotoxicity because lymphocyte metabolism is highly dependent on both salvage and de novo synthesis of guanine nucleotides. (NCI04)
Aqueous extracts of flowers that are used in healing systems.
The alcoholic extract of the bulb or whole garlic plant Allium sativum (Liliaceae) with potential antineoplastic activity. The garlic plant has long been considered a beneficial plant for health and has been used as an antihelmintic, a rubefacient, an anti-infective, and an antihypertensive. Fresh or aged, garlic extracts contain compounds such as diallyl and allyl propyl disulfides with potent antioxidant, cholesterol-lowering properties; regular ingestion may be preventative for atherosclerosis and cardiovascular diseases. (NCI04)
The raw material from which QUININE was extracted.
An herb obtained from the plant Eugenia jambolana. Jambul seeds and fruits have important carminative and astringent properties and may reduce blood sugar levels. This agent contains glucosides, jamboline and ellagic acid which may check the conversion of starch into sugar. Jambul may have chemoprotective and chemopreventive effects. (NCI04)
A malignant germ cell tumor in children arising from the testis. It includes the embryonal carcinoma, yolk sac tumor, choriocarcinoma, and mixed germ cell tumors.
A malignant germ cell tumor in children arising from the ovary. It includes the dysgerminoma, yolk sac tumor, choriocarcinoma, embryonal carcinoma and immature teratoma.
The reemergence of a malignant germ cell tumor in children after a period of remission.
The mesylate salt form of nelfinavir, a synthetic antiviral agent that selectively binds to and inhibits human immunodeficiency virus (HIV) protease. Nelfinavir has activity against HIV 1 and 2.
An oral formulation of the hydrochloride salt of topotecan, a semisynthetic derivative of the quinoline alkaloid camptothecin, with potential antineoplastic activity. Topotecan selectively inhibits topoisomerase I activity by stabilizing topoisomerase I-DNA covalent complexes during the S phase of the cell cycle, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery.
A methylated tyrosine, a catecholamine synthesis antagonist with antihypertensive property. Metyrosine competitively inhibits tyrosine 3-monooxygenase, an enzyme that activates molecular oxygen to catalyze the hydroxylation of tyrosine to dihydroxyphenylalanine (Dopa), an intermediate to catecholamine (dopamine, norepinephrine, and epinephrine) production. This agent reduces the elevated levels of catecholamines associated with pheochromocytoma, thereby preventing hypertension.
The sodium salt form of nedocromil, a pyranoquinolone derivative with anti-inflammatory properties. Nedocromil sodium inhibits the activation and release of inflammatory mediators (leukotrienes, histamine and prostaglandins) from a variety of cells involved in hypersensitivity reactions, including mast cells, eosinophils, neutrophils, macrophages, monocytes and platelets. As a result, nedocromil sodium inhibits both immediate and late bronchoconstriction, decreases bronchial hyperresponsiveness and inhibits recruitment of other inflammatory cells into the airway epithelium.
The maleate salt of amlodipine, a synthetic phenylpyridine vasodilator with antihypertensive and antianginal effects. Amlodipine inhibits the influx of extracellular calcium ions into myocardial and peripheral vascular smooth muscle cells, thereby preventing vascular and myocardial contraction. Furthermore, decreased myocardial contractility and dilation of the main coronary and systemic arteries lead to increased blood flow and oxygen delivery to the myocardial tissue and decreases total peripheral resistance. This agent may also modulate multi-drug response activity through inhibition of the p-glycoprotein efflux pump.
The anhydrous form of the pyridazine angiotensin-converting enzyme (ACE) inhibitor cilazapril with antihypertensive activity. As a prodrug cilazapril is rapidly metabolized in the liver to cilazaprilat; cilazaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II, resulting in vasodilation. Cilazaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
The hydrochloride salt form of tocainide, a primary amine analog of lidocaine exhibiting class 1b antiarrhythmic property. Tocainide hydrochloride stabilizes the neuronal membrane by reversibly binding to and blocking open and inactivated voltage-gated sodium channels. This inhibits the inward sodium current required for the initiation and conduction of impulses and reduces the excitability of myocardial cells. This agent reduces the rate of rise and amplitude, and shortens the action-potential duration (APD) in both the Purkinje and muscle fibers. Tocainide also shortens the effective refractory period (ERP) of Purkinje fibers resulting in an increased the ERP/APD ratio. Overall these effects lead to the slowing of nerve impulses and stabilization of the heartbeat.
The anhydrous form of enalaprilat, a dicarbocyl-containing peptide and angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Enalaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Enalaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A stable coordination compound comprised of sodium valproate and valproic acid with anticonvulsant and antiepileptic activities. Divalproex dissociates to the valproate ion in the gastrointestinal tract. This agent binds to and inhibits gamma-aminobutyric acid (GABA) transaminase and its anticonvulsant activity may be exerted by increasing brain concentration of GABA and by inhibiting enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings. Divalproex may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels.
A benzamide derivative that is used as a dopamine antagonist.
The maleate salt form of pheniramine, an alkylamine derivative with antihistaminic and vasodilatory properties. Pheniramine maleate binds to histamine H1 receptors, thereby inhibiting phospholipase A2 and production of endothelium-derived relaxing factor, nitric oxide. Subsequent lack of activation of guanylyl cyclase through nitric oxide results in decreased cyclic GMP (cGMP) levels, thereby inhibiting constriction of smooth muscle tissue, and decreased capillary permeability and histamine-activated allergic reactions.
The hydrochloride salt of the substituted benzamide metoclopramide, a para-aminobenzoic acid (PABA) derivative that is structurally related to procainamide, with gastroprokinetic and antiemetic activities. Metoclopramide binds to dopamine 2 (D2) receptors in the peripheral nervous system (PNS), antagonizing dopamine-mediated relaxation of gastrointestinal smooth muscle and promoting gastroprokinesis; the pyloric sphincter and the duodenal bulb are relaxed, peristalsis of the duodenum and jejunum increase, and gastric emptying and intestinal transit accelerate. This agent may also increase the resting tone of the lower esophagus sphincter (LES), preventing acid reflux. In the central nervous system (CNS), metoclopramide antagonizes D2 dopamine receptors in the chemoreceptive trigger zone (CTZ) of the medulla, thereby preventing nausea and vomiting.
The phosphate ester of metronidazole, a synthetic nitroimidazole derivative with antiprotozoal and antibacterial activities.
The calcium salt form of fenoprofen, a propionic acid derivative with analgesic, non-steroidal antiinflammatory and antirheumatic properties. Fenoprofen inhibits both isozymes of cyclooxygenase; resulting in prostaglandin synthesis inhibition, thereby blocking the conversion of arachidonic acid to prostaglandins. In addition, fenoprofen activate both peroxisome proliferator activated receptors (PPAR)-alpha and -gamma, by which it may down-regulate leukotriene B4 production.
The tartrate salt form of dobutamine, a synthetic catecholamine with sympathomimetic activity. Dobutamine primarily binds to and stimulates beta-1-adrenergic receptors located in the myocardium. As a result, it leads to a positive inotropic effect and increases in cardiac output.
A long-acting, amide-type local anesthetic. Bupivicaine reversibly binds to specific sodium ion channels in the neuronal membrane, resulting in a decrease in the voltage-dependent membrane permeability to sodium ions and membrane stabilization; inhibition of depolarization and nerve impulse conduction; and a reversible loss of sensation.
The anhydrous, sodium salt form of acetic acid. Sodium acetate anhydrous disassociates in water to form sodium ions (Na+) and acetate ions. Sodium is the principal cation of the extracellular fluid and plays a large part in fluid and electrolyte replacement therapies. Sodium acetate anhydrous is used as an electrolyte replenisher in isosmotic solution for parenteral replacement of acute losses of extracellular fluid without disturbing normal electrolyte balance.
The sodium salt form of azathioprine, a pro-drug of purine analogue with immunosuppressive activity. Azathioprine is converted in vivo to its active metabolite 6-mercaptopurine (6-MP), which substitutes for the normal nucleoside and mistakenly gets incorporated into DNA sequences. This leads to inhibition of DNA, RNA, and protein synthesis. As a result, cell proliferation may be inhibited, particularly in lymphocytes and leukocytes.
Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS.
Infiltration of the skin and subcutaneous tissue by leukemic cells without evidence of leukemia in the bone marrow and peripheral blood. It results in clinically identifiable skin lesions. It may be the first manifestation of acute leukemia, preceding the involvement of the bone marrow and peripheral blood by the leukemic process.
Polycystic liver disease-1 is an autosomal dominant condition characterized by the presence of multiple liver cysts of biliary epithelial origin. Although the clinical presentation and histologic features of polycystic liver disease in the presence or absence of autosomal dominant polycystic kidney disease (see, e.g., PKD1, 173900) are indistinguishable, PCLD1 is a genetically distinct form of isolated polycystic liver disease (summary by Reynolds et al., 2000). A subset of patients (28-35%) may develop kidney cysts that are usually incidental findings and do not result in clinically significant renal disease (review by Cnossen and Drenth, 2014). Genetic Heterogeneity of Polycystic Liver Disease See also PCLD2 (617004), caused by mutation in the SEC63 gene (608648) on chromosome 6q21; PCLD3 (617874), caused by mutation in the ALG8 gene (608103) on chromosome 11p; and PCLD4 (617875), causes by mutation in the LRP5 gene (603506) on chromosome 11q13.
A type of arteriosclerosis in which calcification of the tunica media is the predominant feature.
Vaccines consisting of one or more antigens that stimulate a strong immune response. They are purified from microorganisms or produced by recombinant DNA techniques, or they can be chemically synthesized peptides.
Vaccines or candidate vaccines used to prevent infection with parainfluenza viruses in humans and animals.
Vaccines or candidate vaccines used to prevent infection with RESPIRATORY SYNCYTIAL VIRUSES.
Vaccines that are produced by using only the antigenic part of the disease causing organism. They often require a ""booster"" every few years to maintain their effectiveness.
Vaccines or candidate vaccines used to prevent infection by any virus from the family HERPESVIRIDAE.
Vaccines or candidate vaccines derived from edible plants. Transgenic plants (PLANTS, TRANSGENIC) are used as recombinant protein production systems and the edible plant tissue functions as an oral vaccine.
Vaccines or candidate vaccines used to prevent infection with CYTOMEGALOVIRUS.
Vaccines or candidate vaccines used to prevent STREPTOCOCCAL INFECTIONS.
Vaccines used in conjunction with diagnostic tests to differentiate vaccinated animals from carrier animals. Marker vaccines can be either a subunit or a gene-deleted vaccine.
Virosomes are reconstituted influenza virus (A/Singapore) envelopes. The membrane of these vesicles consists of a spherical, unilamellar lipid bilayer. Purified influenza envelope glycoproteins (hemagglutinin HA and neuramindase NA) are inserted into the lipid bilayer. Virosomes with a bilayer consisting of neutral phospholipids can be used as an unspecific or a specific drug carrier system, while positively charged vesicles can be used as a transfer system for any genetic materials.
Vaccines using VIROSOMES as the antigen delivery system that stimulates the desired immune response.
Any variance from the expected 1:1 ratio for the expression of the two inherited parental alleles for the same gene.
The sequential location of genes on a chromosome.
DEFENSINS found in azurophilic granules of neutrophils and in the secretory granules of intestinal PANETH CELLS.
Infections with bacteria of the genus CHLAMYDOPHILA.
The hydrochloride salt of a saturated derivative of sphingosine. As an inhibitor of protein kinase C (PKC), safingol competitively binds to the regulatory phorbol-binding domain of PKC, a kinase involved in tumorigenesis. This agent has been shown to act synergistically with other chemotherapeutic agents and may potentiate chemotherapy drug-induced apoptosis in vitro and in vivo.
A poorly adsorbed analog of prednisolone, a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. After cell surface receptor attachment and cell entry, prednisolone enters the nucleus where it binds to and activates specific nuclear receptors, resulting in an altered gene expression and inhibition of proinflammatory cytokine production. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis in sensitive tumor cells populations. (NCI)
A glycoprotein complex extracted from Klebsiella pneumoniae K2O1 strain with immunostimulating property. This glycoprotein complex consists of 2 repetitive glycoprotein subunits; P1 comes from the bacterial capsule about 95 kD in molecular mass and F1, having an lipopolysaccharide-related structure (350 kDa), is derived from bacterial external membrane. Although the mechanism of action is not fully elucidated, Klebsiella pneumoniae F1 fraction appears to suppress monocyte apoptosis, hence inducing the differentiation of monocytes into macrophages. Furthermore, this agent also enhances humoral and cell-mediated immune responses, and increases natural killer cell cytotoxicity functions. This glycoprotein has been shown to reduce the incidence of infection.
The sodium salt form of penciclovir, a synthetic acyclic guanine derivative with antiviral activity, mainly used to treat infections from herpes simplex virus (HSV) types 1 and 2. In HSV infected cells, penciclovir is phosphorylated by viral thymidine kinase and subsequently converted by cellular kinases into the active metabolite, penciclovir triphosphate, which competitively inhibits viral HSV polymerase by blocking deoxyguanosine triphosphate substrate binding. As a result, herpes viral DNA synthesis and replication are selectively inhibited.
A functionalized amino acid compound specifically synthesized as an anticonvulsive drug to use as add-on therapy for partial-onset seizures with antinociceptive and neuroprotective activities. Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels without affecting fast inactivation, thereby stabilizing hyperexcitabe neuronal membranes. Furthermore, this agent binds to collapsin response mediator protein 2 (CRMP2; DPYSL2), a cytosolic phosphoprotein expressed in most tissues. In the nervous system, CRMP2 acts as a mediator of growth cone collapse as well as modifies axon number, length, and neuronal polarity.
An inhibitor of cysteine protease with blood platelet aggregation inhibiting activity. Aloxistatin is an irreversible, membrane-permeable inhibitor of lysosomal and cytosolic cysteine proteases with the ability to inhibit calpain activity in intact platelets.
A phenylalanine and cyclohexane derivative that acts as a hypoglycemic agent by stimulating the release of insulin from the pancreas. It is used in the treatment of TYPE 2 DIABETES.
Recombinant form of endogenous Insulin-like Growth Factor 1 exhibiting mitogenic activity. Clinical Use: Diabetes Mellitus and Amyotrophic Lateral Sclerosis.
A vitamin D3 analogue with potential antineoplastic activity. Seocalcitol binds to and activates the vitamin D receptor, a cytoplasmic polypeptide expressed in normal vitamin D responsive tissues, but also overexpressed in certain cancers including hepatocellular carcinoma and pancreatic cancer. Mediated through vitamin D receptor, this agent induces cancer cell differentiation, inhibits cancer cell growth and induces apoptosis. In addition, seocalcitol may also induce growth arrest and apoptosis independent of vitamin D receptor activation through mechanisms that are not fully elucidated.
A succinic acid derivative with hypoglycemic activity. Like other meglitinide-type compounds, mitiglinide has a high affinity for SUR1 subunits.
A covalent conjugate of recombinant interferon alpha and polyethylene glycol (PEG), used as an antiviral and antineoplastic agent. The biological activity of this agent is derived from its interferon alpha protein moiety. Interferons alfa bind to specific cell-surface receptors, leading to the transcription and translation of genes whose protein products mediate antiviral, antiproliferative, anticancer, and immune-modulating effects. The PEG moiety lowers the clearance of interferon alpha, thereby extending the duration of its therapeutic effects, but may also reduce interferon-mediated stimulation of an immune response. (NCI04)
An arabinonucleoside antimetabolite with antineoplastic activity. Nelarabine is demethoxylated by adenosine deaminase to become biologically active 9-beta-D-arabinosylguanine (ara-G); ara-G incorporates into DNA, thereby inhibiting DNA synthesis and inducing an S phase-dependent apoptosis of tumor cells. (NCI04)
A recombinant LONG ACTING INSULIN and HYPOGLYCEMIC AGENT that is used to manage BLOOD GLUCOSE in patients with DIABETES MELLITUS.
The major and active metabolic product of dietary indole-3-carbinol, present in a wide variety of plant food substances from the Cruciferae family, with cytostatic and antiestrogenic properties. 2-(indol-3-ylmethyl)-3,3'-diindolylmethane is an antagonist of estrogen receptor, and could inhibit the proliferation of both estrogen-dependent and -independent breast cancer cells. In addition, this agent also activates binding of the aryl hydrocarbon (Ah) receptor to its cognate DNA responsive element and expression of the Ah receptor-responsive gene CYP1A1.
A derivative of rhodacyanine with potential antineoplastic activity. FJ5002 inhibits telomerase by interfering with holoenzyme assembly and telomere interaction, thus leading to replication-dependent shortening of telomeres with a concurrent increase in aneuploid metaphases and apoptotic cells. Telomerase is active in most tumors cells, but is quiescent in adjacent normal cells. (NCI04)
A synthetic compound that binds to the DNA minor groove and cause anti tumor activity. (NCI)
A long-acting piperidine derivate with selective H1 antihistaminergic and non-sedating properties. Desloratadine diminishes the typical histaminergic effects on H1-receptors in bronchial smooth muscle, capillaries and gastrointestinal smooth muscle, including vasodilation, bronchoconstriction, increased vascular permeability, pain, itching and spasmodic contractions of gastrointestinal smooth muscle. Desloratadine is used to provide symptomatic relieve of allergic symptoms.
An epipodophyllotoxin analogue possessing antineoplastic properties. GL331 binds to and inhibits topoisomerase II, resulting in the accumulation of single- or double-strand DNA breaks, the inhibition of DNA replication and transcription, and apoptotic cell death. (NCI)
A ganciclovir prodrug and antiviral agent that is used to treat CYTOMEGALOVIRUS RETINITIS in patients with AIDS, and for the prevention of CYTOMEGALOVIRUS INFECTIONS in organ transplant recipients who have received an organ from a CMV-positive donor.
A deoxycytidine analog and REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 and HEPATITIS B viruses. It is used to treat HIV INFECTIONS.
A B7 antigen that binds specifically to INDUCIBLE T-CELL CO-STIMULATOR PROTEIN on T-CELLS. It provides a costimulatory signal for T-cell proliferation and cytokine secretion.
5,7,4'-trihydroxy-flavone, one of the FLAVONES.
An orally bioavailable anilinophthalazine with potential antineoplastic activity. Vatalanib binds to and inhibits the protein kinase domain of vascular endothelial growth factor receptors 1 and 2; both receptor tyrosine kinases are involved in angiogenesis. This agent also binds to and inhibits related receptor tyrosine kinases, including platelet-derived growth factor (PDGF) receptor, c-Kit, and c-Fms.
A member of the tyrphostin family of tyrosine kinase inhibitors that exhibits anti-proliferative activity by selectively inhibiting the platelet-derived growth factor receptor tyrosine kinase. It inhibits phosphorylation, uncouples oxidative phosphorylation and induces apoptosis and cell growth arrest in certain cancer cell lines. (NCI)
A sulfonamide derivative and non-steroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic activities. Valdecoxib selectively binds to and inhibits cyclooxygenase (COX)-2, thereby preventing the conversion of arachidonic acid into prostaglandins, which are involved in the regulation of pain, inflammation, and fever. This NSAID does not inhibit COX-1 at therapeutic concentrations and therefore does not interfere with blood coagulation.
A pegylated, recombinant, human growth hormone (GH) structural analog with GH receptor antagonist activity. As a GH analog, the structure of pegvisomant is similar to that of native GH with the exception of 9 amino acid substitutions. Pegvisomant selectively binds to GH receptors on cell surfaces, interfering with endogenous GH receptor binding and so GH signal transduction. Inhibition of GH signal transduction results in decreased serum concentrations of insulin-like growth factor-I (IGF-I), and other GH-responsive serum proteins, including IGF binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS), and may inhibit the growth of cancers in which IGF-1 is upregulated.
A synthetic retinoid with differentiation inducing and potential antineoplastic activities. Like other retinoic acid agents, Ro 16-9100 binds to and activates retinoic acid receptors (RARs), thereby altering the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.
A member of the Tyrphostin family of tyrosine kinase inhibitors that inhibits signal transduction through platelet-derived growth factor receptor and selectively attenuates smooth muscle cell growth. (NCI)
A phosphorothioate antisense oligonucleotide. Targeted to the initiation codon region of the bcl-2 mRNA, oblimersen inhibits bcl-2 mRNA translation, resulting in decreased expression of the bcl-2 protein, an apoptotic inhibitor expressed in some types of cancer and linked to tumor drug resistance. This agent may enhance the efficacy of standard cytotoxic chemotherapy. (NCI04)
A synthetic oligodeoxynucleotide, containing unmethylated CpG motifs derived from bacterial DNA, with immunostimulatory activities. A CpG oligodeoxynucleotide (CpG ODN) binds to and activates a Toll-like receptor 9 (TLR9) and is taken up into cells by endocytosis; once internalized, it may activate numerous signaling transduction pathways resulting in the release of multiple cytokines. Through activation of TLR9, a CpG ODN can directly stimulate B-lymphocytes, dendritic and NK cells, resulting in an increase in innate immunity and antibody-dependant cell cytotoxicity (ADCC). Additionally, a CpG ODN can indirectly modulate T-cell responses, through the release of cytokines (IL-12 and IFN gamma), to induce a preferential shift to the Th1 (helper) phenotype resulting in enhanced CD8+ cellular cytotoxicity.
A sulfonamide triptan with extracerebral, intracranial vasoconstrictor activity. Almotriptan selectively binds to and activates serotonin 5-HT 1B and 1D receptors in the central nervous system (CNS), thereby causing extracerebral, intracranial blood vessel constriction. This may lead to pain relief from vascular headaches. Almotriptan may also relieve vascular headaches by preventing the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater during a migraine, by reducing extravasation of plasma proteins, and by decreasing the release of other mediators of inflammation from the trigeminal nerve.
An amide prodrug of the cyclooxygenase II (COX-2) selective, non-steroidal anti-inflammatory drug (NSAID) valdecoxib, with anti-inflammatory, analgesic, and antipyretic activities. Upon administration, parecoxib is hydrolyzed by hepatic carboxyesterases to its active form, valdecoxib. Valdecoxib selectively binds to and inhibits COX-2. This prevents the conversion of arachidonic acid into prostaglandins, which are involved in the regulation of pain, inflammation, and fever. This NSAID does not inhibit COX-1 at therapeutic concentrations and, therefore, does not interfere with blood coagulation.
A water-soluble, injectable sodium salt form of parecoxib, an amide prodrug of the cyclooxygenase II (COX-2) selective, non-steroidal anti-inflammatory drug (NSAID) valdecoxib, with anti-inflammatory, analgesic, and antipyretic activities. Upon intravenous or intramuscular administration, parecoxib is hydrolyzed by hepatic carboxyesterases to its active form, valdecoxib. Valdecoxib selectively binds to and inhibits COX-2. This prevents the conversion of arachidonic acid into prostaglandins, which are involved in the regulation of pain, inflammation, and fever. This NSAID does not inhibit COX-1 at therapeutic concentrations and, therefore, does not interfere with blood coagulation.
Belongs to a group of antihormone drugs.
A pyrrolo-pyrimidine epidermal growth factor receptor (EGFR) protein kinase inhibitor with anti-tumor activity.PKI-166 reversibly inhibits HER1 and HER2 tyrosine kinases, belong to the epidermal growth factor receptor family, thereby inhibiting tumor growth and metastasis.
A synthetic indolocarbazole protein kinase C (PKC) inhibitor. As a nonspecific inhibitor of protein kinase C enzymes, midostaurin inhibits oncogenic PKC signal transduction pathways involved in the regulation of the cell cycle in tumor cells, thereby initiating tumor cell apoptosis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=257390&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=257390&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1872"" NCI Thesaurus)
A analog of antimetabolite cytarabine (ara-C), with potential antineoplastic activity. Upon administration, thiarabine (T-araC) is phosphorylated to the triphosphate form T-araCTP and competes with cytidine for incorporation into DNA. This results in an inhibition of DNA replication and RNA synthesis, chain termination and may eventually decrease tumor cell proliferation. Compared to ara-C, T-araC appears to have a longer half-life and has a higher efficacy.
A stereoisomer of verapamil and third-generation P-glycoprotein inhibitor. Laniquidar inhibits the drug efflux pump P-glycoprotein, resulting in higher concentrations of antineoplastic agents in tumor cells that are multi-drug resistant due to the overexpression of P-glycoprotein. (NCI04)
A naturally-occurring, orally bioavailable bisbenzylisoquinoline plant alkaloid with potential chemosensitization activity. MDR modulator CBT-1 binds to and inhibits the MDR efflux pump P-glycoprotein (P-gp), which may inhibit the efflux of various chemotherapeutic agents from tumor cells and reverse P-gp-mediated tumor cell MDR. P-gp is a transmembrane ATP-binding cassette (ABC) transporter and is overexpressed by some multidrug resistant tumors.
Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder characterized by short stature, coarse and dysmorphic facies, bowing of the long bones, and vertebral anomalies. Facial features include hypertelorism, bushy eyebrows, micrognathia, small mouth with dental anomalies, low-set ears, and short neck. There is progressive focal bone destruction, including acroosteolysis and generalized osteoporosis. Additional and variable features include hearing loss, renal cysts, and cardiovascular anomalies (summary by Ramos et al., 1998; Simpson et al., 2011; Isidor et al., 2011).
Salts and derivatives of undecylenic acid.
The hydrochloride salt of the nonsteroidal aromatase inhibitor fadrozole with potential antineoplastic activity. Fadrozole specifically inhibits aromatase, blocking the aromatization of androstenedione and testosterone into estrone and estradiol, respectively, the final step in estrogen biosynthesis; the reduction in estrogen levels may inhibit growth in estrogen-dependent cancers. Aromatase, a member of the cytochrome P-450 superfamily, is found in many tissues; overexpression has been linked to the development of preneoplastic and neoplastic changes in breast tissue.
Diminished or absent blood supply to the brain caused by obstruction (thrombosis or embolism) of an artery resulting in neurologic damage.
A sleep disorder characterized by excessive sleepiness.
TBC1D24-related disorders comprise a continuum of features that were originally described as distinct, recognized phenotypes: DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures). Profound sensorineural hearing loss, onychodystrophy, osteodystrophy, intellectual disability / developmental delay, and seizures. Familial infantile myoclonic epilepsy (FIME). Early-onset myoclonic seizures, focal epilepsy, dysarthria, and mild-to-moderate intellectual disability. Progressive myoclonus epilepsy (PME). Action myoclonus, tonic-clonic seizures, progressive neurologic decline, and ataxia. Early-infantile epileptic encephalopathy 16 (EIEE16). Epileptiform EEG abnormalities which themselves are believed to contribute to progressive disturbance in cerebral function. Autosomal recessive nonsyndromic hearing loss, DFNB86. Profound prelingual deafness. Autosomal dominant nonsyndromic hearing loss, DFNA65. Slowly progressive deafness with onset in the third decade, initially affecting the high frequencies.
A sleep disorder characterized by difficulty in falling asleep and/or remaining asleep.
An abnormal connection between arteries and veins characterized by the absence of intervening capillaries in the brain. Signs and symptoms include headaches, bruit upon head examination, seizures, and bleeding. When bleeding occurs, the signs and symptoms are similar to those in stroke.
Absence of wakefulness and conscience, but (in contrast to coma) with involuntary opening of the eyes and movements (such as teeth grinding, yawning, or thrashing of the extremities).
A potent mast cell degranulator. It is involved in histamine release.
A pathological condition characterized by the presence of a number of ESOPHAGEAL DIVERTICULA in the ESOPHAGUS.
A WHO grade I slow growing tumor, more frequently affecting young adults. It is composed of small, uniform, mature cells resembling pineocytes with occasional large pineocytomatous rosettes. It may show a wide range of divergent phenotypes, including neuronal, glial, melanocytic, photoreceptor and mesenchymal differentiation. Pineocytoma generally has a relatively favorable prognosis. (Adapted from WHO)
A 3:1 mixture of alfaxalone with alfadolone acetate that previously had been used as a general anesthetic. It is no longer actively marketed. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1445)
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
A defined, decaffeinated green tea polyphenol mixture isolated from the plant Camellia sinensis with antiviral and antioxidant activities. Polyphenon E may possess chemopreventive properties. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=506041&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=506041&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C38689"" NCI Thesaurus)
Progressive spinal muscular atrophy, i.e., muscular weakness and atrophy related to loss of the motor neurons of the spinal cord and brainstem.
A condition that is characterized by degeneration of the distal phalanges.
A balloon type pouch or bulge in the wall of a cerebral blood vessel.
Ovarian cancer, the leading cause of death from gynecologic malignancy, is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases (Chi et al., 2001). These typical features relate to the biology of the disease, which is a principal determinant of outcome (Auersperg et al., 2001). Epithelial ovarian cancer is the most common form and encompasses 5 major histologic subtypes: papillary serous, endometrioid, mucinous, clear cell, and transitional cell. Epithelial ovarian cancer arises as a result of genetic alterations sustained by the ovarian surface epithelium (Stany et al., 2008; Soslow, 2008).
A synthetic hydroxamic acid derivative with potential antineoplastic activity. Prinomastat inhibits matrix metalloproteinases (MMPs) (specifically, MMP-2, 9, 13, and 14), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. As a lipophilic agent, prinomastat crosses the blood-brain barrier. (NCI04)
A tricyclic acridine-based (or carboxamide-based) drug with dual topoisomerase inhibitor and potential antineoplastic activities. Acridine carboxamide inhibits both topoisomerases I and II and intercalates into DNA, resulting in DNA damage, the disruption of DNA repair and replication, the inhibition of RNA and protein synthesis, and cell death.
Dimers and oligomers of flavan-3-ol units (CATECHIN analogs) linked mainly through C4 to C8 bonds to leucoanthocyanidins. They are structurally similar to ANTHOCYANINS but are the result of a different fork in biosynthetic pathways.
The chloride salt of a radioactive isotope of strontium. Strontium chloride Sr 89 is taken up and incorporated preferentially in metastatic lesions in bone where it emits cytotoxic beta radiation, resulting in an inhibition and/or reduction of tumor growth and so tumor-related bone pain. (NCI04)
A 1,1-bisphosphonate ester with potential antineoplastic and hypocholesterolemic activities. SR-45023A binds to hydroxyapatite crystals in the bone matrix where it inhibits enzymatic activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which is required for the formation of mevalonate, the precursor of cholesterol. Consequently, shortage of mevalonate impedes the synthesis of downstream isoprenoids that are essential for protein prenylation. This leads to the loss of activity of proteins involved in osteoclast function and cellular proliferation, such as Ras and Rho, leading to an inhibition of cellular proliferation, and induction of osteoclasts apoptosis. In addition, SR-45023A activates the farnesoid X activated receptor (FXR), a member of the nuclear hormone superfamily implicated in cholesterol metabolism and bile acid transport and may play a role in this agent's antineoplastic effect.
A recombinant chimeric dual G-CSF and IL-3 receptor agonist. Leridistim binds with high affinity to both the interleukin-3 (IL-3) and granulocyte colony-stimulating factor (G-CSF) receptors, thereby stimulating the production and maturation of neutrophils, platelets, and lymphocytes after chemotherapy. (NCI04)
A pharmacological agent that inhibits the catalytic activity of an enzyme.
A biological process consisting of chromosomal rearrangements and duplications. These phenotypes are often seen in the karyotype of cancer cells, where there is an imbalance between the mechanisms of cell-cycle control and mutation rates within aberrant genes. Ataxia telangiectasia is a disease that is resultant from mutations in the ATM gene, which is a cell cycle checkpoint gene. Nijmegen breakage syndrome is also a disease characterized by chromosomal and genomic instability.
Closure of the ductus arteriosus prior to birth.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the duodenum. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
Spontaneous DEEP VEIN THROMBOSIS of an upper extremity vein, mostly AXILLARY VEIN; and SUBCLAVIAN VEIN. It is frequently precipitated by repetitive physical activity often in young, healthy adults.
Inflammation of the postauricular lymph nodes.
Infection of the oropharynx with, or disease caused by, Candida, especially C. albicans. This disease usually results from debilitation (as in immunosuppression and especially AIDS), physiologic change, prolonged administration of antibiotics, and iatrogenic and barrier breakage. SYN candidosis, moniliasis.
Breakdown of the connection and subsequent leakage of effluent (fluids, secretions, air) from a SURGICAL ANASTOMOSIS of the digestive, respiratory, genitourinary, and cardiovascular systems. Most common leakages are from the breakdown of suture lines in gastrointestinal or bowel anastomosis.
Abnormal calcification of the mitral valve.
A transient increase in blood pressure following a surgical procedure.
Occurence of a patient becoming conscious during a procedure performed under GENERAL ANESTHESIA and subsequently having recall of these events. (From Anesthesiology 2006, 104(4): 847-64.)
Any platelet aggregation process that decreases the rate, frequency or extent of platelet aggregation.
A toxicity of hematopoietic stem cell transplantation that manifests as fever, rash and pulmonary deterioration which becomes evident at marrow engraftment. It occurs unexpectedly and is occasionally fatal. It can occur after an autogeneic or an allogeneic hematopoietic cell transplantation.
A below normal level of saturation of serum transferrin with iron.
An infection of the lymph nodes in the axilla.
Bleeding occurring after a medical intervention.
Fetal embryopathy associated with maternal angiotensis converting enzyme (ACE) inhibitor use during pregnancy that may include fetal acute renal failure, growth restriction, oligohydramnios, calvaria abnormalities, preterm birth, and pulmonary hypoplasia with respiratory distress.
Abnormally high level of fibrinogen in the blood.
An infectious process affecting the pleura.
Reduced fluid intake (drinking) in a clinical situation where the plasma molarity or sodium concentration normally would induce greater fluid intake.
An in vitro decrease in the platelet count.
An abscess that is located in the adrenal gland.
Paralysis of the glossopharyngeal nerve.
Poverty of behavior and speech output, lack of initiative, loss of emotional responses, psychomotor slowing, and prolonged speech latency.
An abnormal thickening of the Achilles tendon.
An electrocardiographic finding of the Q axis from +90 to +180 degrees.
Complications related to damage at the vascular access site. Examples include bleeding, formation of hematoma, aneurysm, pseudoaneurysm, or arteriovenous fistula, development of infection, and catheter thrombosis.
The most common gastric polyp in the Western hemisphere. The lesion consists of a localized hyperplasia of the deep epithelial compartment of the oxyntic mucosa, with variable degrees of cystic dilatation. Malignant transformation is the exception. (WHO, 2000)
Neuropathy, the cause of which is present at birth.
A carcinoma that arises from the eyelid. Examples include basal cell carcinoma and squamous cell carcinoma.
A non-invasive neoplastic process that affects the epithelium of any part of the digestive system. It is characterized by the presence of morphologic features of dysplasia (e.g., architectural and cytological epithelial alterations) or, in a minority of cases, lack of such morphologic features, as in colonic sessile serrated adenomas/polyps.
A form of DELIRIUM which occurs after GENERAL ANESTHESIA.
Genomic instability associated with defective DNA mismatch repair in tumors.
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest.
An aggressive malignant smooth muscle neoplasm, arising from the small intestine. It is characterized by a proliferation of neoplastic spindle cells.
Pancreatic enzymes are comprised primarily of proteases, lipase and amylase that catalyze the breakdown of fats, carbohydrates and proteins during the digestion of food. However, the pancreas also produces many other digestive enzymes such as ribonuclease, deoxyribonuclease, gelatinase and elastase.
A rare genetic disorder characterized by bone marrow failure, spinal abnormalities, saddle nose, and metaphysical striation.
An inflammatory disorder that affects the thyroid gland. It is characterized by the infiltration of the thyroid parenchyma by lymphocytes. It includes Hashimoto thyroiditis and subacute lymphocytic thyroiditis.
The study of the processes by which normal cells, exposed to ionizing radiation, are transformed into cancer cells.
Cancers caused by exposure to carcinogens in the general environment
Rare diseases that have not been well studied.
This category currently includes only malignancies in which there is a well documented association between the neoplastic process and a specific virus as a causative agent.--2003
Course of conduct directed at a specific person that involves repeated (two or more occasions) visual or physical proximity, nonconsensual communication, or verbal, written, or implied threats, or a combination thereof, that would cause a reasonable person fear.
A cancer vaccine adjuvant that consists of an oil droplet emulsion of monophosphoryl lipid A and mycobacterial cell wall skeleton. Detox-B adjuvant is a non-specific immunostimulant that may enhance the host immune response to certain cancer vaccines. Detox-B differs from Detox adjuvant in that Detox-B contains lecithin. (NCI04)
A synthetic vaccine comprised of a peptide consisting of peptide fragments of melanoma-associated antigen 12 (MAGE-12). MAGE-12 has been identified as an epitope recognized by tumor infiltrating lymphocytes (TIL). Vaccination with MAGE-12 peptide stimulates the host immune system to mount a TIL response against tumor cells expressing MAGE-12, potentially resulting in decreased tumor growth.
A radioimmunoconjugate of the humanized monoclonal antibody (MoAb) CC49 labeled with Yttrium 90 (Y-90). MoAb CC49 recognizes the pancarcinoma tumor-associated glycoprotein (TAG)-72 with high affinity. Y-90 MoAb CC49 delivers beta particles emitting Y-90 radionuclide directly to tumor cells that express TAG-72, thereby this agent may be used in radioimmunotherapeutic treatment of cancers.
A radioimmunoconjugate of the humanized monoclonal antibody (MoAb) CC49 labeled with lutetium 131 (Lu-177). MoAb CC49 binds to the pancarcinoma tumor-associated glycoprotein (TAG)-72 with high affinity. Lu-177 MoAb CC49 delivers gamma radiation emitting Lu-177 nuclide directly to tumor cells that express TAG-72, and so may be used in radioimmunotherapeutic treatment of cancers.
Cancer that does not begin in the blood or bone marrow.
A synthetic radioimmunoconjugate comprised of a humanized anti-interleukin-2 (IL-2) antibody linked to the radioisotope Yttrium 90 with potential antineoplastic activity. Daclizumab binds with high affinity to the Tac (also called CD25) subunit of the IL-2 receptor complex and inhibits the binding of IL-2, thereby blocking the IL-2-mediated activation of lymphocytes. As Yttrium Y 90 daclizumab, daclizumab delivers radiation specifically to lymphocytes that express the IL-2 receptor. (NCI04)
A sphingomyelin/cholesterol liposomal formulation of vincristine sulfate with potential antineoplastic activity. Vincristine, a vinca alkaloid isolated from the plant Vinca rosea, irreversibly binds to and stabilizes tubulin, thereby interrupting microtubule assembly/disassembly dynamics, thereby preventing the formation of the mitotic spindle and leading to cell cycle arrest in metaphase. Liposomal encapsulation prolongs bioavailability of vincristine, increases its delivery to tumor tissues and reduces its toxicity profile. Compared to standard liposomal delivery, sphingosomal drug delivery further increases circulation time of serum drug and enhances drug accumulation at tumor sites, thereby leading to a further increase in efficacy.
A formulation containing carmustine dissolved in ethanol for intra-tumoral administration that allows carmustine to enter both aqueous and lipid compartments of the target tissue. As an antineoplastic nitrosourea, carmustine alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis. Carmustine also carbamoylates proteins, including DNA repair enzymes, resulting in an enhanced cytotoxic effect. Carmustine is highly lipophilic and crosses the blood-brain barrier readily.
A radioimmunoconjugate of a mouse monoclonal antibody (MoAb) J591 labeled with Iodine 131 (I-131). MoAb muJ591 recognizes the extracellular domain of the prostate-specific membrane antigen (PSMA) and reacts with tumor vascular endothelium. Using MoAb muJ591 as a carrier for I-131 results in the targeted imaging and/or destruction of cells overexpressed PSM.
A vaccine consisting of a monoclonal antibody (MoAb) directed against an idiotype that mimics a human milk fat globule (HMFG) membrane epitope. Vaccination with monoclonal antibody 11D10 anti-idiotype vaccine induces anti-anti-idiotype antibodies (Ab3) that may react with breast cancer cell lines expressing the HMFG membrane epitope.
A radioimmunotherapeutic agent consisting of a monoclonal antibody (BrE-3) directed against the tumor-associated antigen epithelial glycoprotein mucin chelated to the radioisotope yttrium-90. Yttrium Y 90 monoclonal antibody BrE-3 binds to tumor cells expressing epithelial glycoprotein mucin, selectively delivering a cytotoxic dose of beta radiation. (NCI04)
A humanized monoclonal antibody conjugated to the imaging radioisotope (indium-111). This radioimmunoconjugate binds to the breast epithelial mucin antigen, which is found primarily on breast cancer cells, permitting radioactive immunodetection of mucin-positive tumor cells and an estimate of radiation dosimetry prior to administration of cytotoxic radiotherapy. (NCI04)
A panadenocarcinoma murine monoclonal antibody (MoAb) with potential antineoplastic activity. MoAb m170 recognizes MUC-1 antigen present on the surface of many adenocarcinomas. It may be conjugated with a radioactive element and used in radioimmunotherapy (RIT), a procedure that uses a tumor-specific monoclonal antibody to target radiation to cancer cells.
A radioimmunoconjugate of monoclonal antibody (MoAb) B3 conjugated with isotope yttrium 90. MoAb B3 is a murine MoAb that recognizes a Lewis Y carbohydrate antigen present on the surface of many carcinomas. This radioimmunoconjugate emits beta particles that causes cytotoxicity in tumor cells and has both diagnostic and therapeutic uses.
A radioimmunoconjugate of monoclonal antibody (MoAb) B3 labeled with Indium 111 (In-111). MoAb B3 is a murine MoAb that recognizes a Lewis Y carbohydrate antigen present on the surface of many carcinomas. This radioimmunoconjugate emits gamma radiation and X-Ray photons that can be captured by gamma camera, allowing imaging of Lewis Y expressing tissues.
A synthetic sequence of DNA constructed in the antisense orientation to a sequence of DNA in epidermal growth factor receptor (EGFR), a member of the erbB gene family. EGFR antisense DNA suppresses the expression of EGFR by tumor cells, thereby inhibiting tumor cell proliferation and decreasing tumor growth. This agent also appears to reduce the invasiveness of certain breast cancer cells. Members of the erbB gene family are overexpressed in many cancers and play roles in carcinogenesis and the regulation of cell proliferation. (NCI04)
A cationic cholesterol derivative mixed with dimethylaminoethane-carbamoyl and sonicated to form small unilamellar vesicles that can complex with DNA, DNA/protein complexes and other drug complexes and mediates the delivery into the cytosol from the endosome compartment. (NCI)
A vaccine consisting of recombinant vaccinia virus encoding the tumor-associated antigen carcinoembryonic antigen (CEA) and a TRIad of COstimulatory Molecules (B7-1, ICAM-1, and LFA-3; also called TRICOM). Vaccination with recombinant vaccinia-CEA(6D)-TRICOM vaccine stimulates the host immune system to mount a T-cell response against tumor cells expressing the CEA antigen. The use of TRICOM in the vaccine may elicit a greater antitumor cytotoxic T lymphocyte (CTL) immune response compared to the use of vaccinia-CEA alone.
A cancer vaccine comprised of a recombinant fowlpox virus vector encoding the carcinoembryonic antigen (CEA) and a TRIad of COstimulatory Molecules (B7-1, ICAM-1 and LFA-3) (TRICOM). This agent may enhance CEA presentation to antigen presenting cells (APC) and activate cytotoxic T-cells against CEA-expressing tumors. (NCI04)
A murine IgM monoclonal antibody (MoAb) developed for the potential treatment of graft versus host disease (GvHD). MoAb ABX-CBL recognizes human CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. This MoAb is capable of neutralizing inflammatory reactions via a complement-dependent cytotoxic mechanism. However, MoAb ABX-CBL does not offer an improvement over antithymocyte globulin in the treatment of acute steroid resistant GVHD.
A liposome-encapsulated form of the semi-synthetic doxorubicin analogue annamycin with antineoplastic activity. Annamycin intercalates into DNA and inhibits topoisomerase II, resulting in the inhibition of DNA replication and repair and RNA and protein synthesis. This agent circumvents multidrug-resistance (MDR) transporters, including P-glycoprotein (P-gp). Liposomal annamycin is less toxic and shows improved antitumor activity compared to annamycin.
A 9-residue human leukocyte antigen (HLA)-restricted fragment of carcinoembryonic antigen (CEA). Vaccination with carcinoembryonic antigen peptide 1-6D, which has the amino acid sequence YLSGANLNL, may elicit a cytotoxic T lymphocyte (CTL) immune response against tumors expressing CEA.
A genetically engineered oncolytic virus with potential antineoplastic property. NV1020 is constructed from the herpes simplex virus 1 (HSV-1) by the deletion of a single copy of the gamma (1)34.5 gene and the substitution of the UL23 region of the thymidine kinase (tk) gene with a DNA fragment from HSV-2, thereby resulting in a replication-competent, attenuated virus. This modified virus preferentially transfects rapidly dividing cells, which causes cell lysis in tumor cells. NV1020 has shown reduced virulence against normal tissues and a decreased neurovirulence in comparison with some other modified HSV strains.
Stage I includes: IA: (T1, pN0, M0) and IB: (T1, cN0, M0). T1: Primary tumor equal or less than 2 cm in size. pN0: No regional lymph node metastasis by pathologic examination. cN0: No regional lymph node metastasis by clinical examination. M0: No distant metastasis. (AJCC 7th Ed.)
Stage II includes: IIA: (T2/T3, pN0, M0), IIB: (T2/T3, cN0, M0), and IIC: (T4, N0, M0). T2: Primary tumor greater than 2 cm but not more than 5 cm in maximum dimension. T3: Primary tumor over 5 cm in maximum dimension. T4: Primary tumor invades bone, muscle, fascia, or cartilage. pN0: No regional lymph node metastasis by pathologic examination. cN0: No regional lymph node metastasis by clinical examination. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th Ed.)
Stage III includes: IIIA: (Any T, N1a, M0) and IIIB: (Any T, N1b/N2, M0). N1a: Micrometastasis in regional lymph nodes. N1b: Macrometastasis in regional lymph nodes. N2: In transit metastasis. M0: No distant metastasis. (AJCC 7th Ed.)
The reemergence of Merkel cell carcinoma after a period of remission.
An enzymatic preparation containing proteolytic enzymes papain, trypsin and chymotrypsin with potential anti-inflammatory and anticarcinogenic activities. Papain can be extracted from the fruit of the papaya plant. Trypsin and chymotrypsin are serine proteases produced and secreted by the pancreas. Although its exact mechanisms has yet to be fully illustrated, Wobe-Mugos E appears to have the ability to modulate the immune system by degrading cytokines, and cytokine receptors and clearing circulating immune protein complexes, as well as disrupting adhesion molecules. This agent has been shown to reduce chemotherapy-induced toxicity, inhibit tumor cell proliferation and prolong survival rates.
A bispecific antibody containing a 4G7 hybridoma secreting IgG1 antibody specific for B-lymphocytes and a monoclonal antibody targeting Fc gamma RI-expressing cells.
A radioimmunoconjugate consisting of murine monoclonal antibody (M195) and bismuth 213 (Bi213). Monoclonal antibody M195 binds to CD33, a surface antigen expressed by myelogenous leukemia cells. Bismuth 213 is an isotope that emits short-ranged high-energy alpha particles. This radioimmunoconjugate selectively delivers alpha particle-mediated cytotoxicity to leukemic cells, thereby limiting the exposure of normal tissues to ionizing radiation. (NCI04)
A semi-synthetic triterpene glycoside, derived from the naturally occurring saponins. GPI-0100 functions as an adjuvant when given as part of a vaccine preparation to improve the immunogenicity of antigens such as proteins, carbohydrates. GPI-0100 containing vaccines have been used with both viral and tumor antigens to elicit a Type 1 helper T cell response for those diseases in which a cytotoxic T lymphocyte (CTL) response is desired.
A multivalent vaccine comprised of the epitope antigens of Globo H hexasaccharide 1 (Globo H), GM2 ganglioside, Lewis-Y, MUC1-32-mer, TF(c), and Tn(c) conjugated with keyhole limpet hemocyanin, with potential antineoplastic activity. The antigens included in this vaccine are associated various cancer cells. Vaccination with this multivalent vaccine may induce production of IgG and IgM antibodies as well as an antibody-dependent cell-mediated cytotoxicity (ADCC) against tumors expressing these antigens.
A liposome-encapsulated formulation of paclitaxel, a taxoid compound extracted from the Pacific yew tree Taxus brevifolia, with antineoplastic property. Paclitaxel binds to tubulin and interferes with the assembly/disassembly dynamics of microtubules, thereby resulting in the inhibition of cell division. This agent also induces apoptosis via inactivation of the apoptosis inhibitor, B-cell Leukemia 2 (Bcl-2) protein. Paclitaxel liposome formulation potentially enhances delivery of higher doses of paclitaxel to the target tissues and exhibits lower systemic toxicity.
A water soluble antifolate with anti-proliferative activity. AG2037 inhibits activity of glycinamide ribonucleotide formyltransferase (GARFT), the first folate-dependent enzyme of the de novo purine synthesis pathway essential for cell proliferation. Enzyme inhibition reduces the purine nucleotides pool required for DNA replication and RNA transcription. As a result, this agent causes cell cycle arrest in S-phase, and ultimately inhibits tumor cell proliferation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38329&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38329&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2633"" NCI Thesaurus)
An immunotoxin containing an epitope of human gastrin conjugated to diphtheria toxin, with antineoplastic activity. The gastrin epitope in this vaccine is chemically identical or similar to the endogenous gastrin-17 (G-17), a 17-amino acid peptide hormone that stimulates secretion of gastric acid by the stomach. Diphtheria toxin inhibits protein synthesis via modifying translation elongation factor 2 (EF-2). Vaccination with this immunotoxin may elicit production of antibodies against gastrinoma cells overexpressing gastrin, in addition to the toxic effects on protein synthesis exerted by the diphtheria toxin moiety.
A recombinant peptide consisting of the amino acid residues 540 to 548 of the human telomerase reverse transcriptase (hTERT). Telomerase expression has been directly linked to tumor development; its catalytic subunit is expressed in the majority of human cancer cells, but infrequently in normal cells. Vaccination with telomerase:540-548 peptide may stimulate cytotoxic T cells to recognize and kill telomerase-expressing cells. (NCI04)
A sulfhydryl-based second-generation matrix metalloproteinase (MMP) inhibitor with potential antineoplastic activity. BMS-275291 selectively inhibits several MMPs (MMP 1, 2, 8, 9, and 14), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38088&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38088&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1875"" NCI Thesaurus)
An immunotoxin of monoclonal antibody (MoAb) RFB4 covalently linked to a single deglycosylated ricin toxin A-chain (dgA), originated from castor beans. MoAb RFB4 recognizes CD22 antigen, a B-cell adhesion protein expressed on malignant cells in about 70 percent of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Ricin toxin A-chain, a potent protein synthesis inhibitor, was deglycosylated and was used in this immunoconjugate to avoid hepatic entrapment. This agent limits specific cytotoxicity of ricin toxin to CD22-positive malignant cells.
A low molecular weight agent with antineoplastic activity. Benzoylphenylurea binds to the colchicine binding site on tubulin, thereby blocking tubulin polymerization and disrupting mitotic function. This agent also inhibits DNA polymerase, and has been shown to arrest leukemia cells in the G1-S transition phase of the cell cycle. (NCI04)
A carcinoma that arises from the breast and has metastasized to the skin.
A chimeric peptide immunogen of human epidermal growth factor-2 (HER-2) with antineoplastic property. HER-2 protein is a receptor tyrosine kinase and a tumor-associated antigen (TAA) that is overexpressed in a variety of cancers. MVF-HER-2(628-647)-CRL 1005 vaccine, coated with poloxamer CRL-1005 to form microparticles, consists of a mutated HER-2 B-cell epitope, HER-2(628-647), and a promiscuous T cell epitope (amino acid sequence 288-302) of the measles virus fusion protein (MVF). Vaccination with this immunogen may stimulate the host immune response to mount a cytotoxic T-lymphocyte response against tumor cells that overexpress the HER2 protein, resulting in tumor cell lysis.
A pyrrolidine and benzodioxole derivative that acts a RECEPTOR, ENDOTHELIN A antagonist. It has therapeutic potential as an antineoplastic agent and for the treatment of DIABETIC NEPHROPATHIES.
A synthetic estrogen receptor antagonist. Unlike tamoxifen (which has partial agonist effects) and the aromatase inhibitors (which reduce the estrogen available to tumor cells), fulvestrant binds competitively to estrogen receptors in breast cancer cells, resulting in estrogen receptor deformation and decreased estrogen binding. In vitro studies indicate that fulvestrant reversibly inhibits the growth of tamoxifen-resistant, estrogen-sensitive, human breast cancer cell lines. (NCI04)
Any substance used to reduce hyperglycemia or treat disorders associated with diabetes. Based on their mechanism of action, this class of agents can be classified to the following groups: directly acting insulomimetics, which activates insulin receptors; indirectly acting insulinomimetics, which increase insulin release such as sulfonylureas or which potentiate the effect of insulin such as metformin; those act directly on the metabolism of glucose such as inhibitors of glucosidases and inhibitors of aldose reductase.
The acetate salt of an antimycotic echinocandin lipopeptide, semisynthetically derived from a fermentation product of the fungus Glarea lozoyensis. Caspofungin inhibits 1,3-beta-glucan synthase, resulting in decreased synthesis of beta(1,3)-D-glucan (an essential component of the fungal cell wall), weakening of the fungal cell wall, and fungal cell wall rupture. This agent is active against Aspergillus and Candida species.
A semisynthetic, water-soluble derivative of camptothecin with antineoplastic activity. Exatecan mesylate inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA and inhibiting religation of DNA breaks, thereby inhibiting DNA replication and triggering apoptotic cell death. This agent does not require enzymatic activation and exhibits greater potency than camptothecin and other camptothecin analogues. (NCI04)
A short-acting, aerosolized uridine 5-triphosphate (UTP) solution used as a diagnostic aid for lung cancer. INS316 appears to improve sputum expectoration mediated through the P2Y2 receptor, a nucleotide receptor expressed in human airway epithelial cells and some other tissues. UTP binding to the P2Y2 receptor triggers signal transduction that leads to chloride ion secretion, thereby resulting in mucociliary clearance of airway.
A synthetic silicon-containing agent related to camptothecin with antineoplastic properties. Cositecan stabilizes the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks and consequently triggering apoptosis. Because it is lipophilic, cositecan exhibits enhanced tissue penetration and bio-availability compared to water-soluble camptothecins.
An antineoplastic agent that inhibits the Bcr-Abl fusion protein tyrosine kinase, an abnormal enzyme produced by chronic myeloid leukemia cells that contain the Philadelphia chromosome. Imatinib also inhibits the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF)/c-kit; the SCF/c-kit receptor tyrosine kinase is activated in gastrointestinal stromal tumor (GIST). This agent inhibits proliferation and induces apoptosis in cells that overexpress these oncoproteins.
A disorder also known as complete androgen insensitivity syndrome (CAIS). The 46,XY genetic male totally lacks androgen responsiveness in the target organs thus exhibits a female phenotype.
A cyclic depsipeptide extracted from the Caribbean tunicate Trididemnum cyanophorum. Didemnin B activates caspase, thereby inducing apoptosis, and prevents eukaryotic elongation factor 2 (eEF-2)-dependent translocation, thereby inhibiting protein synthesis. This agent also has immunosuppressive and antiviral properties. (NCI04)
The hydrochloride salt of amantadine, a synthetic tricyclic amine with antiviral, antiparkinsonian, and antihyperalgesic activities. Amantadine appears to exert its antiviral effect against the influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the release of infectious viral nucleic acids into host cells; furthermore, this agent prevents virus assembly during virus replication. Amantadine exerts its antiparkinsonian effects by stimulating the release of dopamine from striatal dopaminergic nerve terminals and inhibiting its pre-synaptic reuptake. This agent may also exert some anticholinergic effect through inhibition of N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine, resulting in antihyperalgesia.
The sodium salt form of thiopental, an ultrashort-acting barbituric acid derivative, with anesthetic activity. Thiopental binds to the chloride ionophore site of the gamma-aminobutyric acid (GABA)-A/chloride ionophore receptor complex, thereby enhancing the inhibitory actions of GABA-A in the brain. This leads to synaptic inhibition, decreased neuronal excitability and induction of anesthesia. In addition, this agent decreases glutamate (Glu) responses.
A non-peptide, kappa-opioid receptor agonist which has also been found to stimulate the release of adrenocorticotropin (ADRENOCORTICOTROPIC HORMONE) via the release of hypothalamic arginine vasopressin (ARGININE VASOPRESSIN) and CORTICOTROPIN-RELEASING HORMONE. (From J Pharmacol Exp Ther 1997;280(1):416-21)
A substance that is being studied in the treatment of osteoporosis in postmenopausal women. Strontium ranelate helps new bone tissue to grow and decreases bone loss. This lowers the risk of bone fractures.
The disodium salt of a synthetic pyrimidine-based antifolate. Pemetrexed binds to and inhibits the enzyme thymidylate synthase (TS) which catalyses the methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) to 2'-deoxythymidine-5'-monophosphate (dTMP), an essential precursor in DNA synthesis.
A broad-spectrum, second generation, triazole compound with antifungal activity. Posaconazole strongly inhibits 14-alpha demethylase, a cytochrome P450-dependent enzyme. Inhibition of 14-alpha-demethylase prevents the conversion of lanosterol to ergosterol, an important component of the fungal cell wall. Inhibition of ergosterol synthesis changes the fungal cell membrane composition and integrity, alters membrane permeability and eventually leads to fungal cell lysis. Compared to other azole antifungals, posaconazole is a significantly more potent inhibitor of sterol 14-alpha demethylase.
Drug combination of artemether and lumefantrine that is used to treat PLASMODIUM FALCIPARUM MALARIA.
A nutritional condition produced by a deficiency of VITAMIN B 6 in the diet, characterized by dermatitis, glossitis, cheilosis, and stomatitis. Marked deficiency causes irritability, weakness, depression, dizziness, peripheral neuropathy, and seizures. In infants and children typical manifestations are diarrhea, anemia, and seizures. Deficiency can be caused by certain medications, such as isoniazid.
A carcinoma that arises from the prostate gland and has spread to other anatomic sites.
A benign well circumscribed neoplasm of hyaline cartilage arising from bone or soft tissue. It is characterized by the presence of chondrocytes.
A malignant neoplasm composed of undifferentiated cells.
The magnesium salt of esomeprazole, the S-isomer of omeprazole, with gastric proton pump inhibitor activity. In the acidic compartment of parietal cells, esomeprazole is protonated and converted into the active achiral sulphenamide; the active sulphenamide forms one or more covalent disulfide bonds with the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting its activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production. H+/K+ ATPase is an integral membrane protein of the gastric parietal cell.
A substance derived from any of several Old World coarse prickly-leaved shrubs and subshrubs including the plant Silybum marianum. Milk thistle's active chemical component is silymarin, which is a combination of flavonoids such as silibinin, dehydrosilibinin, silychristin and silydianin. These compounds are antioxidants and may alter the membrane structure of the liver cell, thereby blocking the absorption of toxins; they may also stimulate the production of new liver cells. In addition, milk thistle may increase cellular adenosine triphosphate (ATP) levels, exhibiting dose-dependent cardiac myocyte cytoprotection against doxorubicin. The silibinin component of milk thistle has been shown to inhibit growth factor receptor-mediated mitogenic and cell survival signaling, thereby inhibiting tumor growth. (NCI04)
The S-isomer of omeprazole, with gastric proton pump inhibitor activity. In the acidic compartment of parietal cells, esomeprazole is protonated and converted into the active achiral sulfenamide; the active sulfenamide forms one or more covalent disulfide bonds with the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting its activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production. H+/K+ ATPase is an integral membrane protein of the gastric parietal cell.
A fluorinated hydrocarbon and gaseous substance used as an imaging contrast agent. After administration in microsphere form, perflutren exhibits lower acoustic impedance than blood and improves ultrasound signaling.
The malate salt of almotriptan, a sulfonamide triptan with vasoconstrictor activity. Almotriptan selectively binds to and activates serotonin 5-HT 1B and 1D receptors in the central nervous system (CNS), thereby causing cerebral blood vessel constriction. This may lead to pain relief from vascular headaches. Almotriptan may also relieve vascular headaches by preventing the release of vasoactive neuropeptides from perivascular trigeminal axons in the dura mater during a migraine, by reducing extravasation of plasma proteins, and by decreasing the release of other mediators of inflammation from the trigeminal nerve.
A cloprostenol derivative that is used as an ANTIHYPERTENSIVE AGENT in the treatment of OPEN-ANGLE GLAUCOMA and OCULAR HYPERTENSION.
A cloprostenol-derived amide that is used as an ANTIHYPERTENSIVE AGENT in the treatment of OPEN-ANGLE GLAUCOMA and OCULAR HYPERTENSION.
A hydrochloride salt form of valganciclovir, a prodrug form of ganciclovir, a nucleoside analog of 2'-deoxyguanosine, with antiviral activity. After phosphorylation, valganciclovir is incorporated into DNA, resulting in inhibition of viral DNA polymerase, and viral replication.
Dietary fiber source, extracted from rind of citrus fruits, and used as a gelling agent.
A recombinant urate oxidase enzyme isolated from a genetically-modified strain of Saccharomyces cerevisiae. Urate oxidase catalyzes the oxidation of uric acid to the excretable metabolite allantoin, a molecule that is 5-10 times more water-soluble than uric acid. An enzyme that occurs endogenously in most mammals, urate oxidase is not found in humans. (NCI04)
A recombinant analog of the endogenous cytokine erythropoietin, an erythropoiesis-stimulating protein. Due to the addition of two carbohydrate chains, darbepoetin alfa exhibits a three-fold greater half-life than does erythropoietin. Similar to erythropoietin, darbopoietin alfa binds to and activates epoetin receptors, thereby inducing the differentiation and maturation of erythrocyte progenitors, stimulating endothelial cell proliferation, and stimulating B-cell proliferation and immunoglobulin production. (NCI04)
A drug combination of fluticasone and salmeterol that is used as an inhaler formulation to manage the symptoms of ASTHMA and CHRONIC OBSTRUCTIVE PULMONARY DISEASE.
A fixed combination of two protease inhibitors, lopinavir and ritonavir, used to treat human immunodeficiency virus (HIV) infection. The ritonavir in the combination drug increases the concentration and biological half-life of lopinavir but is not present in sufficient concentration to act as a protease inhibitor.
A dry powdered inhaler formulation of fluticasone-salmeterol drug combination.
Name of the FDA approved preparation from J&J.
A tyrosine kinase inhibitor and ANTINEOPLASTIC AGENT that inhibits the BCR-ABL kinase created by chromosome rearrangements in CHRONIC MYELOID LEUKEMIA and ACUTE LYMPHOBLASTIC LEUKEMIA, as well as PDG-derived tyrosine kinases that are overexpressed in gastrointestinal stromal tumors.
A small, yellow citrus fruit that is a source of citric acid and ascorbic acid (vitamin C). The juice is used to flavor food and drink and to prevent scurvy. Lemon oil (scented liquid taken from the peel) is used in aromatherapy. The scientific name of the lemon tree is Citrus limon.
An extract of Uncaria tomentosa (U. tomentosa), also called Cat's claw, a native Amazonian plant belonging to the Rubiaceae species, with potential anti-inflammatory, immunomodulating, antioxidant and antineoplastic activities. Although the exact mechanism(s) by which U. tomentosa extract exerts its effect(s) has yet to be fully elucidated, this extract may inhibit the proliferation of certain types of cancer cells. This extract may modulate inflammatory and immune responses through the stimulation of T- and B-lymphocytes and certain cytokines, including interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-a). Components in U. tomentosa may both induce repair of chemically-induced DNA damage and scavenge free radicals, which may protect against reactive oxygen species (ROS)-mediated cellular damage. In addition, this extract stimulates myelopoiesis, which may prevent chemotherapy-induced neutropenia.
An extract of the rhizome of the perennial plant Zingiber officinale with potential antineoplastic activity. Ginger extract contains a number of different phenolic compounds, some of which have displayed antineoplastic, anti-inflammatory, and antioxidant activities. This agent also exhibits antiemetic properties.
A benign adipose tissue neoplasm originating in the colon. It is the second most common benign lesion of the colon after benign adenomatous polyps. Older patients are more likely to be affected, and most lesions are located at the right side of large bowel. Colon lipomas may lead to intestinal obstruction.
Narrowing of the lumen of the pancreatic duct.
A term used to describe the state or condition of substance use data.
Presence or formation of GALLSTONES in the GALLBLADDER.
Leukopenia that occurs in the neonatal period.
A non-metastasizing neoplasm that arises from the male reproductive system. Representative examples include benign prostate phyllodes tumor, benign Sertoli cell tumor, seminal vesicle cystadenoma, and epididymal adenomatoid tumor.
A non-neoplastic dental disorder that is present at birth.
A type of weakness that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
Bleeding originating in the organs and tissue that aid in reproduction.
A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. It is said to be the third leading cause of death in the United States. Gunel and Lifton (1996) noted that about 20% of strokes are hemorrhagic, resulting in bleeding into the brain. Ischemic strokes, resulting from vascular occlusion, account for the majority of strokes. Bersano et al. (2008) reviewed genetic polymorphisms that have been implicated in the development of stroke. Candidate genes include those involved in hemostasis (see, e.g., F5; 612309), the renin-angiotensin-aldosterone system (see, e.g., ACE; 106180), homocysteine (see, e.g., MTHFR; 607093), and lipoprotein metabolism (see, e.g., APOE; 107741). See also hemorrhagic stroke, or intracerebral hemorrhage (ICH; 614519).
A form of ischemia-reperfusion injury occurring in the early period following transplantation. Significant pathophysiological changes in MITOCHONDRIA are the main cause of the dysfunction. It is most often seen in the transplanted lung, liver, or kidney and can lead to GRAFT REJECTION.
Gastroenteritis resulting from an infection with cytomegalovirus.
Presence of nitrites in the urine. [OHSU:jpgourdine, PMID:27377945]
An infectious process affecting the tissues around the orbit.
An infectious process affecting the anal area.
An episode of MYOCARDIAL ISCHEMIA that generally lasts longer than a transient anginal episode that ultimately may lead to MYOCARDIAL INFARCTION.
A sporadic or less frequently familial neoplasm, arising from the glandular epithelium of the stomach, small intestine, biliary tract, colon, and rectum. It is a polypoid or flat circumscribed lesion. Morphologically, it is characterized by a proliferation of neoplastic glandular cells and it is associated with dysplasia. According to the growth pattern, it may be classified as tubular, villous, or tubulovillous. The dysplasia is classified as mild, moderate, or severe. The frequency of malignant transformation depends on the size of the lesion and the degree of dysplasia. Larger adenomas with severe dysplastic changes (sometimes called carcinoma in situ) carry a higher risk of progressing to invasive adenocarcinoma. Gastrointestinal adenomas may present as solitary or multifocal lesions. Familial adenomas tend to be multifocal and carry a higher risk of malignant transformation.
Breaking or tearing of the amniotic membranes during childbirth leading to the leakage of amniotic fluid and the progression of labor.
An infectious process affecting the spleen. Predisposing factors include immunosuppression, diabetes mellitus, and sickle cell anemia. Infectious agents include bacteria (e.g., staphylococcus and streptococcus) and fungi.
An infectious process affecting the pancreas.
An abnormality of the cerebral white matter.
A congenital or acquired abnormality of the wall of the trachea. In congenital cases, there is lack of rigidity in the cartilage of the tracheal wall. In acquired cases, the cartilage of the tracheal wall is degenerated, secondary to tracheostomy or prolonged presence of a breathing tube, or as a complication of a tracheoesophageal fistula surgical repair. Symptoms include stridor, noisy breathing, and upper respiratory infections.
An immune response to foreign (donor) antigens.
An adenocarcinoma that arises from the ovary. It is the most common type of ovarian carcinoma. It includes the serous adenocarcinoma, mucinous adenocarcinoma, clear cell adenocarcinoma, and endometrioid adenocarcinoma.
An abnormal communication between the renal pelvis and another anatomic site.
Fetal cystic hygromas are congenital malformations of the lymphatic system appearing as single or multiloculated fluid-filled cavities, most often in the neck. They are thought to arise from failure of the lymphatic system to communicate with the venous system in the neck. They often progress to hydrops and cause fetal death (Chervenak et al., 1983).
A syndrome that occurs after therapeutic infusion of antibodies into the blood and is characterized by nausea, headache, tachycardia, hypotension, rash, and shortness of breath. It is caused by the release of cytokines from the cells that are targeted by the antibodies. Most patients experience a mild to moderate reaction; however, the reaction may be severe and life-threatening.
A state of hypoperfusion that does not support normal organ perfusion or function. It can include periods of reduced, unstable, or abnormal blood pressure with near syncope, or episodes of syncope.
Endothelial decompensation that is manifested by opacity of the cornea. The condition often occurs as a nonspecific response to mechanical injury from incidental corneal contact by intraocular instruments during surgery; chemical injury from the improper use of intraocular drugs, drugs containing preservatives, or from residues from inadequate rinsing of detergents or other residues from surgical instruments. The most common causes of corneal endothelial decompensation in the adult population are cataract removal/IOL-related endothelial loss and Fuchs dystrophy. When severe, corneal endothelial decompensation requires corneal transplantation.
Displacement of the intraocular lens from the visual axis.
A rare but serious transfusion-related reaction in which fluid builds up in the lungs unrelated to excessively high infusion rate and/or volume (TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD). Signs of Transfusion-Related Acute Lung Injury include pulmonary secretions; hypotension; fever; DYSPNEA; TACHYPNEA; TACHYCARDIA; and CYANOSIS.
Non-infectious pyrexia secondary to malignancy; it may be attributable to cytokines elaborated by neoplasms, and is a diagnosis of exclusion.
A congenital variant of a coronary artery in which a portion of an epicardial coronary artery (most frequently the middle segment of the left anterior descending artery) takes an intramuscular course.
A bacterial, viral, or fungal infectious process affecting the urethra.
McKusick-Kaufman syndrome (MKS) is characterized by the combination of postaxial polydactyly (PAP), congenital heart disease (CHD), and hydrometrocolpos (HMC) in females and genital malformations in males (most commonly hypospadias, cryptorchidism, and chordee). HMC in infants usually presents as a large cystic abdominal mass arising out of the pelvis, caused by dilatation of the vagina and uterus as a result of the accumulation of cervical secretions from maternal estrogen stimulation. HMC can be caused by failure of the distal third of the vagina to develop (vaginal agenesis), a transverse vaginal membrane, or an imperforate hymen. Cardiac malformations that have been described at least once in individuals with MKS include atrioventricularis (AV) communis with a left-sided superior vena cava, atrial septal defect, ventricular septal defect, AV canal, small aorta and hypoplastic left ventricle, tetralogy of Fallot, and patent ductus arteriosus.
A form of adrenal insufficiency related to a lack of ACTH, which leads to a decrease in the production of cortisol by the adrenal glands. Aldosterone production is not usually affected.
Blockage of venous return (flow of blood from the periphery back towards the right atrium) in a vein.
Recurrent narrowing or constriction of a coronary artery following surgical procedures performed to alleviate a prior obstruction.
A disorder that is caused by pathologic changes in the ocular vasculature.
An increased concentration of 4-hydroxy-L-proline the urine.
A malignant neoplasm that affects the area of the nipple in males.
A primary or metastatic malignant tumor involving the lymph node. Lymphomas and metastatic carcinomas are representative examples. -- 2004
An abnormally high level of uric acid in the urine.
A condition that is characterized by venous dilation, which presents as soft, compressible lesions.
The multiple, potentially reversible changes in body systems brought about by physical inactivity and disuse.
A reaction to the infusion of pharmacological or biological substances. Symptoms may appear within minutes to hours following the infusion and may include pruritus, flushing, swelling, dyspnea, bronchospasm, and hypotension.
Incomplete development of the pituitary gland.
A rare carcinoma that arises from the retroperitoneal space.
A carcinoma that arises from the major or minor salivary glands. Representative examples include carcinoma ex pleomorphic adenoma, adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma.
Inflammation of the mucous membranes lining the nose and paranasal sinuses.
Transient pallor of the skin caused by reduced blood flow to the affected region.
Leakage of blood into the dialysate during hemodialysis due to apparatus malfunction.
Infiltration of the meninges by an acute or chronic leukemia.
Ovarian or testicular dysfunction associated with high levels of gonadotropins.
A malignant neoplasm that affects the area of the nipple in females.
A benign or malignant epithelial neoplasm that arises anywhere in the ductal system of the breast. This category includes intraductal papilloma, intraductal papillary carcinoma, ductal hyperplasia with or without atypia, and ductal carcinoma in situ.
Cutaneous involvement by an acute or chronic leukemia.
A subtype of delusional disorder characterized by the central delusional theme that the individual is being malevolently treated (for example, maligned, harassed, conspired against, poisoned or drugged) by another person or group.
A primary or metastatic malignant neoplasm that affects the rectum. Representative examples include carcinoma, lymphoma, and sarcoma.
A coagulation disorder characterized by the partial or complete absence of tissue factor (factor III) activity in the blood.
A polypoid lesion that arises from the colon or rectum and protrudes into the lumen. This group includes adenomatous polyps, serrated polyps, and hamartomatous polyps.
Thrombus formation within an apparatus that carries blood outside of the body, such as pheresis, dialysis or extracorporeal membrane oxygenation (ECMO).
Pneumonia acquired during a hospital stay.
A sensation of discomfort secondary to sampling of tissue or bodily fluid.
An inborn condition characterized by deficiencies of red cell precursors that sometimes also includes LEUKOPENIA and THROMBOCYTOPENIA.
A chalky white area that appears on a tooth surface indicating the presence of decalcified enamel and the potential to advance to cavitation.
A stable synthetic analog of methionine enkephalin (ENKEPHALIN, METHIONINE). Actions are similar to those of methionine enkephalin. Its effects can be reversed by narcotic antagonists such as naloxone.
A saturated solution of formaldehyde, water, and typically another agent, most commonly methanol. In its typical form, formalin is 37% formaldehyde by weight (40% by volume), 6-13% methanol, and the rest water.
The hydrobromide salt form of galantamine, a tertiary alkaloid obtained synthetically or naturally from the bulbs and flowers of Narcissus and several other genera of the Amaryllidaceae family with anticholinesterase and neurocognitive-enhancing activities. Galantamine competitively and reversibly inhibits acetylcholinesterase, thereby increasing the concentration and enhancing the action of acetylcholine (Ach). In addition, galantamine is a ligand for nicotinic acetylcholine receptors, which may increase the presynaptic release of Ach and activate postsynaptic receptors. This agent may improve neurocognitive function in mild and moderate Alzheimer' s disease and may reduce abstinence-induced cognitive symptoms that promote smoking relapse.
A congenital disorder characterized by the complete absence of gonadal tissue.
The sodium salt of methotrexate, an antimetabolite with antineoplastic and immunomodulating properties. Methotrexate binds to and inhibits the enzyme dihydrofolate reductase, resulting in inhibition of purine nucleotide and thymidylate synthesis and, subsequently, inhibition of DNA and RNA syntheses. Methotrexate also exhibits potent immunosuppressant properties. (NCI04)
A common form of DYSTONIA due to involuntary sustained or spasmodic, repetitive muscle contractions in the neck region. According to the position of the twisted neck and head, cervical dystonia can be categorized as torticollis, laterocollis, retrocollis, and a combination of these abnormal postures.
A multicellular process that regulates the number of transmembrane receptors, by means of increased internalization or decreased expression of the transmembrane receptor. This process is involved in dampening the response to extracellular signals.
A selective D1 dopamine receptor agonist used primarily as a research tool.
A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.
A positive regulatory process that increases ligand-receptor interactions. Increase in receptor binding after ligand exposure can result from receptor activation, aggregation, increase in half-life, and/or an increase in gene expression that leads to de novo receptor synthesis.
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and several individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Mutations in the MVK gene have been found to cause multiple types of porokeratosis, which have been described as porokeratosis of Mibelli, porokeratoma, genital porokeratosis, hyperkeratotic porokeratosis, and linear porokeratosis. The preferred title of this entry was formerly 'Porokeratosis 1, Mibelli Type; POROK1.' Genetic Heterogeneity of Porokeratosis Also see porokeratosis-2 (POROK2; 175850), mapped to chromosome 12q24; POROK3 (175900), caused by mutation in the MVK gene (251170) on chromosome 12q24; POROK4 (607728), mapped to chromosome 15q25-q26; POROK5 (612293), mapped to chromosome 1p31; POROK6 (612353), mapped to chromosome 1p31; POROK7 (614714), caused by mutation in the MVD gene (603236) on chromosome 16q24; POROK8 (616063), caused by mutation in the SLC17A9 gene (612107) on chromosome 20q13; and POROK9 (616631), caused by mutation in the FDPS gene (134629) on chromosome 1q22. A palmoplantar form of punctate porokeratosis has also been described (PPKP2; 175860). Genotype/Phenotype Correlations Zhang et al. (2015) screened 12 isoprenoid genes in 134 Chinese probands with porokeratosis and identified mutations in the MVK, MVD, PMVK, and FDPS genes in 113 patients. The authors noted that giant plaque-type porokeratosis ptychotropica with lesion diameters of at least 5 cm appeared to be uniquely associated with mutation in MVK; it was observed in 19 (50%) of 38 MVK probands, but not in patients with mutations in any of the other 3 genes or in the 21 probands in whom no mutation was found. MVK patients also showed the widest range in terms of the number and size of lesions, as well as presence of porokeratosis subtypes. In patients with MVD mutations, the age of onset ranged from 5 to 70 years, and lesion diameters were generally less than 2 cm. In addition, 6 of the 62 MVD probands exhibited solar facial porokeratosis, which was not seen in any other patients. Localized genital porokeratosis and porokeratoma appeared to be uniquely associated with mutation in the PMVK gene, whereas patients with mutations in the FDPS gene had more than 500 lesions, all with diameters of 1 cm or less.
An adenoma or carcinoma arising from the follicular cells of the thyroid gland. It is composed of large oncocytic cells with abundant granular eosinophilic cytoplasm.
Allergic reaction to wheat that is triggered by the immune system.
Inhibitors of the fusion of HIV to host cells, preventing viral entry. This includes compounds that block attachment of HIV ENVELOPE PROTEIN GP120 to CD4 RECEPTORS.
Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.
Hypergonadotropic ovarian failure is a heterogeneous disorder that, in the most severe forms, is a result of ovarian dysgenesis. Ovarian dysgenesis accounts for about half the cases of primary amenorrhea (Timmreck and Reindollar, 2003). Genetic Heterogeneity of Ovarian Dysgenesis Even in its isolated form, 46,XX ovarian dysgenesis is etiologically heterogeneous. See ODG2 (300510), caused by mutation in the BMP15 gene (300247); ODG3 (614324), caused by mutation in the PSMC3IP gene (608665); ODG4 (616185), caused by mutation in the MCMDC1 gene (610098); ODG5 (617690), caused by mutation in the SOHLH1 gene (610224); ODG6 (618078), caused by mutation in the NUP107 gene (607617); ODG7 (618117), caused by mutation in the MRPS22 gene (605810); and ODG8 (618187), caused by mutation in the ESR2 gene (601663). See also ovarian dysgenesis with sensorineural deafness, or Perrault syndrome (233400).
A condition characterized by the inheritance of a chromosome pair from one parent and no chromosomal copies from the other parent. It results in developmental abnormalities or rare recessive disorders. Examples of uniparental disomy include the Prader-Willi syndrome and Angelman syndrome.
Any of the four forms, alpha, beta, gamma and delta, of a member of the vitamin E family, with potential hypocholesterolemic, antithrombotic, antioxidant, immunomodulating and antineoplastic activities. Tocotrienol inhibits the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, thereby lowering cholesterol levels. In addition, tocotrienol acts through multiple signal transduction pathways to induce cell cycle arrest and caspase-mediated apoptosis, and to decrease tumor cell proliferation. In addition, this agent may inhibit angiogenesis through the blockage of vascular endothelial growth factor receptor (VEGFR) and the subsequent inhibition of tumor cell-induced vessel formation. Also, this agent prevents free radical formation and inhibits lipid peroxidation, thereby preventing DNA cell damage. Tocotrienol farnesyl isoprenoid side chains contain 3 double bonds, which are absent in tocopherols, likely contribute to its anti-cancer activities.
Hypertrophic cardiomyopathy (HCM) is typically defined by the presence of unexplained left ventricular hypertrophy (LVH). Such LVH occurs in a non-dilated ventricle in the absence of other cardiac or systemic disease capable of producing the observed magnitude of increased LV wall thickness, such as pressure overload (e.g., long-standing hypertension, aortic stenosis) or storage/infiltrative disorders (e.g., Fabry disease, amyloidosis). The clinical manifestations of HCM range from asymptomatic LVH to progressive heart failure to sudden cardiac death (SCD), and vary from individual to individual even within the same family. Common symptoms include shortness of breath (particularly with exertion), chest pain, palpitations, orthostasis, presyncope, and syncope. Most often the LVH of HCM becomes apparent during adolescence or young adulthood, although it may also develop late in life, in infancy, or in childhood.
Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.
Any quinolone antibiotic with a fluorine (F) atom attached to the quinolone structure, with broad-spectrum antibacterial activity. Fluoroquinolones diffuse through the bacterial cell wall and act by inhibiting bacterial topoisomerase II, DNA gyrase and/or bacterial topoisomerase IV, which are enzymes involved in bacterial DNA replication. This prevents DNA replication and leads to a blockage of bacterial cell proliferation.
Clinical conditions caused by an abnormal sex chromosome constitution (SEX CHROMOSOME ABERRATIONS), in which there is extra or missing sex chromosome material (either a whole chromosome or a chromosome segment).
A group of inflammatory rheumatic diseases associated with arthritis and enthesitis, and often involving the axial skeleton. The most common form of spondyloarthritis is ankylosing spondylitis. Other forms include axial spondyloarthritis, peripheral spondyloarthritis, reactive arthritis, psoriatic arthritis/spondylitis and enteropathic arthritis/spondylitis.
Heterogeneous group of arthritic diseases sharing clinical and radiologic features. They are associated with the HLA-B27 ANTIGEN and some with a triggering infection. Most involve the axial joints in the SPINE, particularly the SACROILIAC JOINT, but can also involve asymmetric peripheral joints. Subsets include ANKYLOSING SPONDYLITIS; REACTIVE ARTHRITIS; PSORIATIC ARTHRITIS; and others.
Group of alkaloids containing a benzylpyrrole group (derived from TRYPTOPHAN)
The enzymatic addition of a sequence of adenylyl residues at the 3' end of an RNA molecule.
Infections with POLYOMAVIRUS, which are often cultured from the urine of kidney transplant patients. Excretion of BK VIRUS is associated with ureteral strictures and CYSTITIS, and that of JC VIRUS with progressive multifocal leukoencephalopathy (LEUKOENCEPHALOPATHY, PROGRESSIVE MULTIFOCAL).
A highly fatal contagious disease of goats and sheep caused by PESTE-DES-PETITS-RUMINANTS VIRUS. The disease may be acute or subacute and is characterized by stomatitis, conjunctivitis, diarrhea, and pneumonia.
Clinically severe acute disease of cattle caused by noncytopathic forms of Bovine viral diarrhea virus 2 (DIARRHEA VIRUS 2, BOVINE VIRAL). Outbreaks are characterized by high morbidity and high mortality.
Denys-Drash syndrome is a condition that affects the kidneys and genitalia.Denys-Drash syndrome is characterized by kidney disease that begins within the first few months of life. Affected individuals have a condition called diffuse glomerulosclerosis, in which scar tissue forms throughout glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Denys-Drash syndrome, this condition often leads to kidney failure in childhood. People with Denys-Drash syndrome have an estimated 90 percent chance of developing a rare form of kidney cancer known as Wilms tumor. Affected individuals may develop multiple tumors in one or both kidneys.Although males with Denys-Drash syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female (ambiguous genitalia) or the genitalia appear completely female. The testes of affected males are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. As a result, males with Denys-Drash are typically unable to have biological children (infertile).Affected females usually have normal genitalia and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome.
Frasier syndrome is a rare disorder defined by pseudohermaphroditism and progressive glomerulopathy (Frasier et al., 1964; Haning et al., 1985; Kinberg et al., 1987). Patients present with normal female external genitalia, streak gonads, and XY karyotype, and frequently develop gonadoblastoma (Blanchet et al., 1977). Glomerular symptoms consist of childhood proteinuria and nephrotic syndrome, characterized by nonspecific focal and segmental glomerular sclerosis, progressing to end-stage renal failure in adolescence or early adulthood. Wilms tumor is not a usual feature (Barbaux et al., 1997).
Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.
An oral dietary supplement containing a natural cyclic monoterpene and major component of the oil extracted from citrus peels with potential chemopreventive and antitumor activities. Although the mechanism of action has yet to be fully elucidated, limonene and its metabolites perillic acid, dihydroperillic acid, uroterpenol and limonene 1,2-diol may inhibit tumor growth through inhibition of p21-dependent signaling and may induce apoptosis via the induction of the transforming growth factor beta-signaling pathway. In addition, they inhibit post-translational modification of signal transduction proteins, resulting in G1 cell cycle arrest as well as differential expression of cell cycle- and apoptosis-related genes.
A synthetic analog of fumagillin, an antibiotic isolated from the fungus Aspergillus fumigatus fresenius with antineoplastic activity. TNP-470 binds to and irreversibly inactivates methionine animopeptidase-2 (MetAP2), resulting in endothelial cell cycle arrest late in the G1 phase and inhibition of tumor angiogenesis. This agent may also induce the p53 pathway, thereby stimulating the production of cyclin-dependent kinase inhibitor p21 and inhibiting angiogenesis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41725&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=41725&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1298"" NCI Thesaurus)
A hydrochloride salt form of famotine, an isoquinoline antiviral agent with activity against myxoviruses and paramyxoviruses.
The hydrochloride salt form of methoxyamine, an alkoxyamine with potential chemotherapeutic adjuvant activity. Methoxyamine covalently binds to apurinic/apyrimidinic DNA damage sites and thereby inhibits base excision repair (BER) process, which may prevent repair of DNA strand breaks and result in an induction of apoptosis. This agent may potentiate the anti-tumor activity of alkylating agents.
The hydrochloride form of exaprolol, a lipophilic derivative of the adrenergic blocking agent propranolol with sympatholytic activity. Exaprolol competitively binds to and blocks beta-adrenergic receptors in the heart and vascular smooth muscle, thereby causing negative chronotropic and inotropic effects leading to a reduction in cardiac output.
An ansamacrolide and maytansine analogue originally isolated from the Ethiopian shrub Maytenus serrata with antineoplastic activity. Ansamitomicin P-3 binds to tubulin at the maytansine-binding site, thereby inhibiting microtubule assembly, inducing microtubule disassembly, and disrupting mitosis.
The hydrochloride salt of an anthracenyl bishydrazone with antineoplastic activity. Bisantrene intercalates with and disrupts the helical structure of DNA, resulting in DNA single-strand breaks, DNA-protein crosslinking, and inhibition of DNA replication. This agent is similar to doxorubicin in activity, but unlike doxorubicin, does not exhibit cardiotoxicity.
The hyrochloride salt form of amorolfine, a morpholine antifungal agent. Amorolfine inhibits delta-14-reductase and delta-7,8-isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membrane.
The fumarate salt form of linogliride, a guanidine-based insulin secratogogue and structural analogue of pirogliride with hypoglycemic activity. Linogliride blocks ATP-sensitive potassium channels on the membranes of pancreatic beta cells which stimulates the secretion of insulin and improves glucose tolerance.
The sodium salt form of darglitazone, an agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic and anti-inflammatory activities. Darglitazone may be able to abrogate acute cerebral inflammatory responses via its suppression of proinflammatory gene expression.
The hydrochloride salt form of boxidine, an agent that inhibits the transformation of 7-dehydrocholesterol to cholesterol and also inhibits sterol absorption.
An orally bioavailable receptor tyrosine kinase inhibitor. SU6668 binds to and inhibits the autophosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), thereby inhibiting angiogenesis and cell proliferation. SU6668 also inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit, often expressed in acute myelogenous leukemia cells. (NCI04)
A 3-cyanoquinoline pan-ErbB tyrosine kinase inhibitor with potential antineoplastic activity. EKB-569 irreversibly binds covalently to epidermal growth factor receptors (EGFR) ErbB-1, -2 and -4, thereby inhibiting receptor phosphorylation and signal transduction and resulting in apoptosis and suppression of proliferation in tumor cells that overexpress these receptors. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=352165&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=352165&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2713"" NCI Thesaurus)
A topical nonsteroidal anti-inflammatory drug that is used in eye drops for the treatment of eye pain and swelling.
A selective aldosterone receptor antagonist. Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, thereby decreasing sodium resorption and subsequently increasing water outflow. This leads to a decrease in blood pressure. Eplerenone is used in the treatment of hypertension and congestive heart failure.
The hydrate of tatirelin, a thyrotropin releasing hormone (TRH) analogue with potential neuroprotective, analgesic and central nervous system-stimulating (CNS)/analeptic activities. Taltirelin mimics the physiological actions of TRH on the CNS while exerting a minimal effect on the release of thyrotrophin (TSH) from the anterior lobe of the pituitary. Like TRH, the mechanism of action of this agent in the CNS has not been fully elucidated mechanism, but may involve various cerebral monoamine pathways. Compared to TRH, taltirelin has a much longer half-life and duration of effects.
A synthetic, highly lipophilic derivative of camptothecin, with potential antineoplastic and radiosensitizing activities. 7-tert-butyldimethylsilyl-10-hydroxycamptothecin binds to and stabilizes the topoisomerase I-DNA covalent complex. This inhibits the religation of topoisomerase I-mediated single-stranded DNA breaks and produces lethal double-stranded DNA breaks when encountered by the DNA replication machinery, thereby inhibiting DNA replication and inducing apoptosis. Camptothecin readily undergoes hydrolysis at physiological pH, changing its conformation from the active lactone structure to an inactive carboxylate form. Modifications on the E ring of camptothecin prevent binding of human serum albumin, which prefers the inactive carboxylate form, thereby enhancing the stability of the active lactone structure and resulting in prolonged agent activity. In addition, this agent sensitizes tumor cells toward radiation treatment.
A second generation polyamine analog synthesized through the restriction of molecular conformations of parent polyamine compounds with potential antineoplastic activity. SL-11047 may displace endogenous polyamines from DNA binding sites, thereby interfering with cell cycle processes dependent upon polyamine binding and function, and resulting in cell-cycle arrest, induction of apoptosis, depletion of polyamines, and interference with gene and ligand-receptor activities involved with cell growth. This agent may exhibit decreased toxicity and enhanced cytotoxicity profiles compared to first-generation polyamine compounds. In tumor cells, there is an increase dependence on polyamines as well as a dysregulated polyamine metabolic pathway resulting in abnormal or sustained tumor growth. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=467739&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=467739&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C60816"" NCI Thesaurus)
A nitro-oxazine and thiazole derivative that is used as a broad spectrum neonicotinoid insecticide.
The disodium salt of a water-soluble phosphate derivative of a natural stilbenoid phenol derived from the African bush willow (Combretum caffrum) with potential vascular disrupting and antineoplastic activities. Upon administration, the prodrug fosbretabulin is dephosphorylated to its active metabolite, the microtubule-depolymerizing agent combretastatin A4, which binds to tubulin dimers and prevents microtubule polymerization, resulting in mitotic arrest and apoptosis in endothelial cells. In addition, this agent disrupts the engagement of the endothelial cell-specific junctional molecule vascular endothelial-cadherin (VE-cadherin) and so the activity of the VE-cadherin/beta-catenin/Akt signaling pathway, which may result in the inhibition of endothelial cell migration and capillary tube formation. As a result of fosbretabulin's dual mechanism of action, the tumor vasculature collapses, resulting in reduced tumor blood flow and ischemic necrosis of tumor tissue.
A natural polyketide compound isolated from the myxobacterium Sorangium cellulosum. Also known as desoxyepothilone B, epothilone D binds to tubulin and inhibits the disassembly of microtubules, resulting in the inhibition of mitosis, cellular proliferation, and cell motility. (NCI04)
A recombinant dimeric fusion protein consisting of the extracellular CD2-binding domain of the human leukocyte function-associated antigen 3 (LFA-3; CD58) linked to the Fc portion of human immunoglobulin G1 (IgG1) with potential immunosuppressive activity. Alefacept binds to the CD2 receptor expressed on the majority of T lymphocytes, blocking the binding of endogenous LFA-3, located on antigen-presenting cells (APCs), to the CD2 receptor; the activation and proliferation of T lymphocytes in response to LFA-3 binding is thus inhibited. In addition, binding of the IgG1 moiety of this agent to the Fc gamma receptor on the surface of natural killer (NK)cells may bridge NK cells and target T lymphocytes, initiating NK cell-mediated apoptosis of T lymphocytes.
A dodecylthio-phenylacetanilide derivative with hypocholesterolemic and anti-atherosclerotic properties. Eflucimibe is an inhibitor of acyl-Coenzyme A:cholesterol acyltransferase (ACAT), an intracellular enzyme which catalyzes the esterification of cholesterol into cholesteryl esters and is believed to be involved in intestinal cholesterol absorption, lipoprotein assembly in the liver, steroid hormone production in the adrenal cortex, and foam cell formation in atherosclerotic lesions.
An arabinoxylane polysaccharide composed of the hemicellulose-Beta extract of rice bran, treated with enzymes from Shiitake mushrooms, that exerts antitumor and antiviral activity by increasing the level of natural killer cells activation. (NCI)
An orally bioavailable quinazoline with potential antineoplastic and radiosensitizing activities. CI-1033 binds to the intracellular domains of pan-erbB tyrosine kinases, irreversibly inhibiting their signal transduction functions and resulting in tumor cell apoptosis and suppression of tumor cell proliferation. This agent also acts as a radiosensitizing agent and displays synergistic activity with other chemotherapeutic agents. erbB is a member of the epidermal growth factor receptor (EGFR) family and is implicated in the malignant transformation of many solid tumors, including breast, ovarian, prostate, lung, and brain cancers. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38403&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38403&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1880"" NCI Thesaurus)
A synthetic metallotexaphyrin with radiosensitizing and chemosensitizing properties. Motexafin gadolinium accumulates in tumor cells preferentially due to their increased rates of metabolism, generating reactive oxygen species (ROS) intracellularly and lowering the tumor cell apoptotic threshold to ionizing radiation and chemotherapy. (NCI04)
A novel small molecule, and a phosphoramidate derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine with antitumor property. NB1011 is selectively active against tumor cells expressing high levels of thymidylate synthase (TS), a critical enzyme in DNA biosynthesis and its over-expression is associated with many solid tumors. This agent is different from the current TS-targeted drugs, which require inhibition of TS to be effective, while cytotoxicity of NB1011 depends upon activation by TS and is independent of tumor suppressor p53. Although the mechanism of action is unclear, NB1011 appears to induce expressions of bax (pro-apoptotic Bcl-2 family member), p21 and GADD45, both are involving in check point control of cell cycle. Activation of these genes results in deregulation of cell cycle and leads to apoptosis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38549&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38549&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1882"" NCI Thesaurus)
A statin with antilipidemic and potential antineoplastic activities. Rosuvastatin selectively and competitively binds to and inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a precursor of cholesterol. This leads to a decrease in hepatic cholesterol levels and increase in uptake of LDL cholesterol. In addition, rosuvastatin, like other statins, exhibits pro-apoptotic, growth inhibitory, and pro-differentiation activities in a variety of tumor cell types; these antineoplastic activities may be due, in part, to inhibition of the isoprenylation of Ras and Rho GTPases and related signaling cascades.
An orally bioavailable inhibitor of acyl-Coenzyme A:cholesterol acyltransferase (ACAT) that prevents cholesterol deposition in the arterial wall. Research was discontinued due to difficulties in assaying the effects of avasimibe on preventing plaque formation and due to its ability to increase the activity of Cytochrome P450 3A4, thus increasing the removal of other drugs from the body.
A synthetic decapeptide and antagonist of naturally occurring gonadotropin-releasing hormone (GnRH). Abarelix directly and competitively binds to and blocks the gonadotropin releasing hormone receptor in the anterior pituitary gland, thereby inhibiting the secretion and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone. As a result, this may relieve symptoms associated with prostate hypertrophy or prostate cancer, since testosterone is required to sustain prostate growth.
An imidazoquinolinamine and Toll-like receptor (TLR) agonist with potential immune response modifying activity. Resiquimod exerts its effect through the TLR signaling pathway by binding to and activating TLR7 and 8 mainly on dendritic cells, macrophages, and B-lymphocytes. This induces the nuclear translocation of the transcription activator NF-kB as well as activation of other transcription factors. This may lead to an increase in mRNA levels and subsequent production of cytokines, especially interferon-alpha (INF-a) and other cytokines, thereby enhancing T-helper 1 (Th1) immune responses. In addition, topical application of resiquimod appears to activate Langerhans' cells, leading to an enhanced activation of T-lymphocytes. Due to its immunostimulatory activity, this agent may potentially be useful as a vaccine adjuvant.
An orally available, long-acting inhibitor of phosphodiesterase (PDE) type 4 (PDE4), with anti-inflammatory and potential antineoplastic activities. Upon administration, roflumilast and its active metabolite roflumilast N-oxide selectively and competitively bind to and inhibit PDE4, which leads to an increase of both intracellular levels of cyclic-3',5'-adenosine monophosphate (cAMP) and cAMP-mediated signaling. cAMP prevents phosphorylation of spleen tyrosine kinase (SYK) and abrogates activation of the PI3K/AKT/mTOR signaling pathway, which may result in the induction of apoptosis. PDE4, a member of the PDE superfamily that hydrolyses cAMP and 3',5'-cyclic guanosine monophosphate (cGMP) to their inactive 5' monophosphates, is upregulated in a variety of cancers and may contribute to chemoresistance; it also plays a key role in inflammation, especially in inflammatory airway diseases.
A humanized monoclonal antibody directed against the C-epsilon 3 domain of immunoglobulin E. Olizumab binds to this IgE domain, thereby preventing IgE from binding to its high-affinity mast-cell receptor. (NCI04)
A synthetic derivative of hydroxamic acid with antineoplastic properties, Pyroxamide inhibits histone deacetylases involved in transcription; induces hyperacetylation of core histones, modulating chromatin structure and affecting transcription of some genes that inhibit tumor growth; and induces growth arrest and apoptosis. Pyroxamide is used in clinical studies for cancer chemotherapy. (NCI04)
An antibody-drug conjugate (ADC) composed of an as of yet publicly unknown monoclonal antibody against a tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of SC-002 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action.
An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody against a tumor-associated antigen (TAA) linked to a currently undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of SC-004 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an unknown mechanism of action.
An oligomeric proanthocyanidin extracted from grape seeds. IH636 grape seed proanthocyanidin extract exhibits dose-dependent free-radical scavenging and antioxidant properties.
A radiolabeled macromolecule consisting of the chelating agent diethylenetriamine pentaacetic acid (DTPA) and mannose each attached to a dextran backbone and labeled with metastable technetiumTc-99 (Tc-99m), with mannose binding and radioisotopic activities. Upon injection, the mannose moiety of technetium Tc 99m-labeled tilmanocept binds to mannose-binding protein (MBP). As MBPs reside on the surface of dendritic cells and macrophages, this gamma-emitting macromolecule tends to accumulate in lymphatic tissue where it may be imaged using gamma scintigraphy. This agent exhibits rapid clearance from the injection site, rapid uptake and high retention within the first draining lymph node, and low uptake by the remaining lymph nodes. MBP is a C-type lectin that binds mannose or fucose carbohydrate residues, such as those found on the surfaces of many pathiogens, and once bound activates the complement system.
A modified citrus pectin exhibiting antimetastatic activity. GBC-590 binds to and inhibits galectin-3 receptor, resulting in mitigation of the metastatic process. (NCI)
Diluted extracts isolated from plants and minerals, including belladonna, arnica, St. Johns wort, and Echinacea. As a homeopathic mouth rinse preparation, Traumeel S exhibits antiinflammatory activity; the mechanism of action has not been fully elucidated. This agent may reduce the severity and duration of treatment-related stomatitis. (NCI04)
A long-acting beta-2 adrenergic agonist and isomer of formoterol with bronchodilator activity. Arformoterol selectively binds to and activates beta-2 adrenergic receptors in bronchiolar smooth muscle, thereby causing stimulation of adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased intracellular cAMP levels cause relaxation of bronchial smooth muscle and lead to a reduced release of inflammatory mediators from mast cells. This may eventually lead to an improvement of airway function.
The presence in a cell of a chromosome pair that is composed of both homologous chromosomes from one parent.
The presence in a cell of a chromosome pair that is composed of duplicates of one parental chromosome.
A natural tocopherol and one of the most potent antioxidant tocopherols. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. It has four methyl groups on the 6-chromanol nucleus. The natural d form of alpha-tocopherol is more active than its synthetic dl-alpha-tocopherol racemic mixture.
The similarity between chromosome segments or chromosomes in the linear arrangement of genes (GENE ORDER) or genetic markers.
Infections with viruses of the order NIDOVIRALES. The concept includes ARTERIVIRUS INFECTIONS and CORONAVIRIDAE INFECTIONS.
The hydrochloride salt of an anthrapyrazole antineoplastic antibiotic. Teloxantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair, as well as RNA and protein synthesis
The hydrochloride salt of acodazole, a synthetic imidazoquinoline with antineoplastic activity. Acodazole intercalates into DNA, resulting in disruption of DNA replication. Use of this agent has been associated with significant cardiotoxicity.
An orally bioavailable receptor tyrosine kinase inhibitor. SU6668 binds to and inhibits the autophosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), thereby inhibiting angiogenesis and cell proliferation. SU6668 also inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit, often expressed in acute myelogenous leukemia cells. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38421&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38421&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1884"" NCI Thesaurus)
A synthetic analog of 2-deoxyguanosine with antiviral activity against hepatitis B virus (HBV). Entecavir is activated in vivo to a 5-triphosphate metabolite. In turn, the triphosphate form competes with the natural substrate deoxyguanosine triphosphate (dGTP) for incorporation into viral DNA. The incorporation of the activated triphosphate metabolite of entecavir inhibits the reverse transcriptase (RT) viral RNA-dependent HBV DNA polymerase and, so, the replication of viral DNA and transcription.
A cyclic Arg-Gly-Asp peptide with potential antineoplastic activity. Cilengitide binds to and inhibits the activities of the alpha(v)beta(3) and alpha(v)beta(5) integrins, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis. (NCI04)
A benzenesulfonamide derivative and phosphodiesterase type 5 (PDE5) inhibitor with vasodilatory activity. Vardenafil selectively inhibits PDE5, thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa and corpus spongiosum of the penis. The inhibition of cGMP degradation results in prolonged muscle relaxation, vasodilation, and blood engorgement of the corpus cavernosa, prolonging penile erection.
A non-nucleoside reverse transcriptase inhibitor. Capravirine shows antiviral activity against wild-type HIV as well as HIV strains with mutations in reverse transcriptase. Due to no statistically-significant difference between standard triple-drug HIV therapies and the same therapy with capravirine, its development was discontinued by the developer.
A sulfone and pyridine derivative that acts as a cyclooxygenase-2 inhibitor. It is used as a NSAID for the treatment of pain associated with RHEUMATOID ARTHRITIS and ANKYLOSING SPONDYLITIS. It is also used for the short-term treatment of moderate postoperative dental pain.
A polyatomic ion whose formula is HCO3-.
Impairment of verbal communication skills, often resulting from brain damage.
Organic substances belonging to diverse chemical families and present in foods in minute amounts, Vitamins are essential to normal metabolism and biochemical functions, usually as coenzymes. Vitamins can be classified by solubility: lipo-soluble (vitamins A, D, E, K, F) and water-soluble (B- complex). Lack of one or more vitamins in the diet cause metabolic deficiency diseases. (NCI04)
An active immunizing agent used to prevent infection by the bacterium Streptococcus pneumoniae. Pneumococcal 7-valent conjugate vaccine consists of a solution of saccharides of the capsular antigens of Streptococcus serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F individually conjugated to diphtheria CRM 197 protein.
A synthetic radiopharmaceutical in which human serum albumin (HSA) is radiolabelled with iodine 131. Upon intravenous injection, iodine-131 human serum albumin is slowly deiodinated in vivo, releasing radioactive iodide that is taken up by thyroid gland. Iodine-131 primarily emits beta particles and has a half-life of 8 days. (NCI04)
The hydrochloride salt of amodiaquine, an orally active 4-aminoquinoline derivative with antimalarial and anti-inflammatory properties. Similar in structure and activity to chloroquine, amodiaquine is effective against some chloroquine-resistant strains, particularly Plasmodium falciparum, the most deadly malaria parasite. Although the mechanism of plasmodicidal action has not been fully elucidated, like other quinoline derivatives, amodiaquine likely is able to inhibit heme polymerase activity in the body. This results in accumulation of free heme, which is toxic to the parasites.
A sterile, freeze dried fraction of human plasma containing factor VIII coagulant antigen and both the inactive and active forms of coagulation factors II (prothrombin), VII, IX and X, with factor VIII (FVIII) inhibitor bypassing activity. Upon reconstitution and infusion, anti-inhibitor coagulant complex is able to, either directly or indirectly, activate thrombin, which facilitates the formation of fibrin from fibrinogen. This results in clot formation. In hemophilic patients, antibodies formed against factor VIII prevent factor VIII activation and impair thrombin formation; anti-inhibitor coagulant complex can both overcome the inhibitory activity of the antibodies and facilitate hemostasis in hemophilic patients.
The hydrochloride salt of a bisdioxopiperazine with iron-chelating, chemoprotective, cardioprotective, and antineoplastic activities. After hydrolysis to an active form that is similar to ethylenediaminetetraacetic acid (EDTA), dexrazoxane chelates iron, limiting the formation of free radical-generating anthracycline-iron complexes, which may minimize anthracycline-iron complex-mediated oxidative damage to cardiac and soft tissues. This agent also inhibits the catalytic activity of topoisomerase II, which may result in tumor cell growth inhibition.
The sodium salt form of fomivirsen, an antisense phosphorothioate oligodeoxynucleotide (ODN) with potent antiviral property. Fomivirsen is a 21-nucleotide ODN complementary to mRNA of the immediate-early region 2 of human cytomegalovirus (CMV). Hybridization of this antisense ODN to CMV mRNA prevents RNA transcription from the immediate-early region 2 gene, thereby inhibiting viral replication. In addition, this agent inhibits adsorption of CMV into host cells via a sequence-independent mechanism. Overall, fomivirsen inhibits viral propagation via inhibiting viral replication and viral uptake by host cells, hence delaying progression of CMV-associated retinitis.
The sodium salt of indomethacin, a methylated indole derivative with anti-inflammatory, analgesic-antipyretic and tocolytic effects. Indomethacin is a non-selective, reversible, and competitive inhibitor of cyclooxygenases 1 and 2, thereby blocking the conversion of arachidonic acid into prostaglandin precursors. Consequently, prostaglandin synthesis is decreased, and prostaglandin-mediated activities are prevented, including pain, inflammation, fever and uterine contraction.
A synthetic version of naturally occurring interferons that have immunomodulatory, antiviral and antiproliferative activities. It may exert antitumor activity by anti-angiogenic and cell differentiation activities. (NCI)
The acetate salt form of magnesium. Magnesium is a divalent cation essential for a number of biochemical processes involved in nerve signaling, bone mineralization and muscle contractions. About 350 enzymes involved in glycolysis and the Krebs cycle, formation of cyclic-AMP and ATP, cellular signal transduction and protein and nucleic acid synthesis are dependent on magnesium.
The hydrated acetate salt form of magnesium. Magnesium is a divalent cation essential for a number of biochemical processes involved in nerve signaling, bone mineralization and muscle contractions. About 350 enzymes involved in glycolysis and the Krebs cycle, formation of cyclic-AMP and ATP, cellular signal transduction and protein and nucleic acid synthesis are dependent on magnesium.
A chemical reagent containing at least any one of the many phosphoric acid derivatives, usually in salt form. The phosphoric salt may be one of three types: strongly acid monometallic, neutral or mildly alkaline dimetallic, and strongly alkaline tri-metallic. Phosphate buffers are typically adjusted to maintain a certain pH or are ""buffered"" with other chemical compounds. Phosphate reagents are used in research laboratories, medicine or industry in various technical procedures. (NCI04)
The pentasodium salt of samarium Sm 153 lexidronam, a therapeutic agent consisting of a medium energy beta- and gamma-emitting radioisotope, samarium Sm 153, and a teraphosphonate chelator, ethylenediaminetetramethylene phosphonic acid (EDTMP). The chelator moiety of samarium Sm 153 lexidronam associates with hydroxyapatite crystals concentrated in areas of bone turnover, thereby selectively delivering samarium Sm 153-mediated cytotoxic radiation to osteoblastic bone metastases.
a drug made of the substance obtained from elder plant
A synthetic derivative of dioxolo-benzodiazepine with anti-seizure activity. Talampanel antagonizes the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) subtype of glutamate excitatory amino acid receptors and may inhibit the growth of gliomas by interfering with neurotransmitters involved in brain tumor growth. This agent may also protect against traumatic brain injury.
The presence of pancreatic tissue outside the normal pancreas, in many cases along the foregut and proximal midgut.
Seed isolated from one of several species of the plant genus Linum. Flaxseed-derived foods, lignans, and essential fatty acids such as alpha-linolenic acid, possess anti-inflammatory, lipid-lowering, antioxidant, and antineoplastic properties.
A nitrovinyl furan used as a schistosomicidal agent and proposed for trypanosomiasis, especially Chagas disease.
A chimeric monoclonal antibody that functions as an ANTINEOPLASTIC AGENT through its binding to the EPIDERMAL GROWTH FACTOR RECEPTOR, where it prevents the binding and signaling action of cell growth and survival factors.
A species of Bifidobacterium that occurs in the LARGE INTESTINE of humans and other mammals and in FERMENTED DAIRY PRODUCTS. It is used as a PROBIOTIC.
A standardized ginkgo biloba extract with antioxidant and neuroprotective activities. EGb761 has been shown to inhibit the proliferation of certain tumor cells in vitro. (NCI04)
The juice of the beetroot, with potential antioxidant and protective activities. Beetroot juice contains antioxidants, including betacyanin, which scavenge free radicals. In addition, beetroot contains high levels of nitrates and folic acid. Consumption of beetroot juice leads to the conversion of nitrate to nitric oxide (NO) in the body. This juice may have a beneficial effect on blood flow and blood pressure through the induction of NO-mediated vasodilation. Additionally, this agent may decrease fatigue and increase physical performance.
Membranous areas between cranial bones in a newborn that appear depressed or sunken.
Increased period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount.
Epilepsy that is refractory to treatment.
Transmission of light through the iris as visualized upon slit lamp examination or infrared iris transillumination videography. The light passes through defects in the pigmentation of the iris.
A group of disorders characterized by the presence of an abnormal inner layer of the cornea. This abnormality results in iris distortion, corneal swelling, pupil distortion, and glaucoma. It usually affects only one eye.
Acquired hemophilia A (AHA) is a rare,often severe, hematological autoimmune disorder characterized by spontaneous hemorrhages into the skin, muscles, soft tissues,or mucous membranes.
A complication of rheumatic disease that is caused by excessive activation and uncontrolled proliferation of T lymphocytes and well-differentiated macrophages. It is characterized by fever, pancytopenia, liver insufficiency, coagulopathy and neurologic symptoms.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 17 in somatic cells.
Mitochondrial Damage involves any process that leads to dysfunction of mitochondria, whether by oxidative damage, mutation of mitochondrial DNA or other by means.
An infectious process related to a central venous catheter.
Calcification, that is, pathological deposition of calcium salts in the aorta.
A decreased anteroposterior thickness of the cornea.
Aberrant mesenchymal cell growth within the placenta. It may be associated with Beckwith-Wiedemann Syndrome.
A benign extrauterine tumor composed of mature adipocytes and smooth muscle cells.
A rare malignant soft tissue neoplasm that occurs primarily in the pancreas.
A rare neurofibroma that affects the heart.
Average platelet volume above the upper limit of the normal reference interval.
Average platelet volume below the lower limit of the normal reference interval. [DDD:wouwehand]
An infectious disorder of newborn infants that is characterized by a systemic inflammatory response within 72 hours of life and is most commonly caused by bacteria.
Mosaic trisomy 8 is a chromosomal disorder defined by the presence of three copies of chromosome 8 in some cells of the organism. The disorder has manifestations of facial dysmorphism, mild intellectual deficit and joint, urinary, cardiac and skeletal anomalies. Most patients present a moderate intellectual deficit with some patients having a normal intelligence. Mosaic trisomy 8 is the result of a post-zygotic event.
A congenital condition described by the presence of symmetric or asymmetric angular deformity and shortening of the long bones, particularly the femurs, tibiae and ulnae. Prevalence is unknown. It manifests at radiography as posteromedial bowing with cortical thickening along the concavity of the curvature and, in some cases, diaphyseal broadening. Bowing of the long bones can be detected on antenatal ultrasound screening, but it is a nonspecific sign that can be associated with a variety of conditions, whose recognition is important for differentiating those that will resolve spontaneously from those that require surgery or other treatment.
An infection that is caused by Campylobacter jejuni.
An adenocarcinoma that arises from the ovary and is characterized by the presence of cystic structures. It includes the serous cystadenocarcinoma, mucinous cystadenocarcinoma, and clear cell cystadenocarcinoma.
An adenocarcinoma arising from the appendix, characterized by the presence of mucinous stroma formation and cystic structures.
An infection caused by the BK virus. It usually causes an asymptomatic infection, except in immunocompromised individuals where it may cause nephropathy or hemorrhagic cystitis.
Serum sample with a grossly white (milk-like, i.e., lactescent) appearance. This feature is indicative of an extremely elevated serum triglyceride level.
A malignant germ cell tumor that arises from the testis and has spread to another anatomic site.
An infectious disorder of newborn infants that is characterized by a systemic inflammatory response beyond 72 hours of life and is most commonly caused by bacteria.
Allergic disposition to the substance derived from the mold rather than the intact mold organism itself.
ANTIMONY salt of meglumine that is used in the treatment of LEISHMANIASIS.
The allelic disorders of free sialic acid metabolism – Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD) ? are neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. The mildest phenotype is Salla disease, which is characterized by normal appearance and neurologic findings at birth followed by slowly progressive neurologic deterioration resulting in mild to moderate psychomotor retardation, spasticity, athetosis, and epileptic seizures. The most severe phenotype is ISSD, characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood.
An orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Otamixaban has a short half-life of 1.5 to 3 hours.
A chimeric IgG1 monoclonal antibody directed against CD80, the natural ligand for the T-cell antigen CD28 which mediates T-cell and B-cell adhesion. Galiximab binds to CD80 expressed on the cell surfaces of follicular lymphomas, resulting in antibody-dependent cell-mediated cytotoxicity (ADCC). CD80 is expressed on activated B-cells and gamma-interferon-stimulated monocytes and is often expressed at low levels on the surfaces of follicular lymphoma cells and other lymphoid malignancies.
A synthetic imidazole derivative and angiotensin II receptor antagonist with antihypertensive activity. Olmesartan selectively binds to the angiotensin type 1 (AT1) receptor subtype in vascular smooth muscle and adrenal gland, thereby competing with angiotensin II for binding to the AT1 receptor. This prevents angiotensin II-induced vasoconstriction and interferes with angiotensin II-mediated aldosterone secretion, thereby decreasing aldosterone production and preventing aldosterone-stimulated sodium retention and potassium excretion.
A synthetic glucopyranoside with antithrombotic activity. Fondaparinux selectively binds to antithrombin III, thereby potentiating the innate neutralization of activated factor X (Factor Xa) by antithrombin. Neutralization of Factor Xa inhibits its activity and interrupts the blood coagulation cascade, thereby preventing thrombin formation and thrombus development.
A vaccine consisting of recombinant vaccinia virus encoding a TRIad of COstimulatory Molecules (B7-1, ICAM-1, and LFA-3; also called TRICOM). Vaccination with recombinant vaccinia-TRICOM vaccine stimulates the host immune system to mount a non-specific T-cell response. With the addition of a tumor-associated antigen peptide, this vaccine may enhance a tumor-specific immune response.
A yeast glycolipid biosurfactant with potential antineoplastic activity. Mannosylerythritol lipid activates protein kinase signal cascades, resulting in cell differentiation, condensation of chromatin, DNA fragmentation, G1 phase cell-cycle arrest, and apoptosis of tumor cells. (NCI04)
A novel sulfonamide compound with potential antineoplastic activity. Indisulam inhibits cyclin-dependent kinases (CDK), which regulate cell cycle progression and are usually over-expressed in cancerous cells. Inhibition of CDK results in G1/S phase arrest of the cell cycle, and may lead to induction of apoptosis and inhibition of tumor cell proliferation. In addition, indisulam also inhibits carbonic anhydrases (CA), especially isoforms IX and XII that are involved in aqueous humor production and are highly overexpressed in some types of cancers. Inhibition of CA IX and XII results in interference with ion exchange and pH in hypoxic tumor tissue and preventing chemoresistance to weakly basic antineoplastic agents.
A 33-epi-chloro-derivative of the ascomycin macrolactam with immunosuppressant property. Pimecrolimus binds to the receptor macrophilin-12 (FKBP-12) forming a complex that blocks the calcium-dependent signal transduction cascade mediated by calcineurin. Via dephosphorylation, calcineurin is the enzyme responsible for activating nuclear factor of activated T-cells (NF-AT), a T cell transcriptional regulatory factor. As a consequence, the synthesis and release of Th1- (T helper 1) and Th2- (T helper 2) type cytokines, and other inflammatory mediators from T-cells and mast cells are blocked and the expression of signals essential for the activation of inflammatory T-lymphocytes is inhibited. However, pimecrolimus mode of action is cell-selective and does not affect Langerhans' cells/dendritic cells and primary fibroblasts.
The sodium salt form of fondaparinux, a synthetic glucopyranoside with antithrombotic activity. Fondaparinux sodium selectively binds to antithrombin III, thereby potentiating the innate neutralization of activated factor X (Factor Xa) by antithrombin. Neutralization of Factor Xa inhibits its activity and interrupts the blood coagulation cascade, thereby preventing thrombin formation and thrombus development. (NCI05)
A pro-drug, fumaric acid salt form of tenofovir, a nucleoside reverse transcriptase inhibitor analog of adenosine. Tenofovir disoproxil fumarate is prescribed to treat HIV and chronic hepatitis B virus (HBV) in adults.
The succinate salt form of frovatriptan, a synthetic triptan with serotonin (5-HT) receptor agonist activity. Frovatriptan succinate binds selectively and with high affinity to 5-HT 1B and presynaptic 5-HT 1D receptors in the extracerebral and intracranial arteries. This leads to an inhibition of serotonin activity and results in vasoconstriction of the painfully dilated blood vessels during migraine attack. Frovatriptan succinate is indicated for the acute treatment of migraine. (NCI05)
A 25-mer antisense oligodeoxynucleotide phosphorothioate. GEM-92 is complementary to the gag mRNA of human immunodeficiency virus type 1 (HIV-1), resulting in HIV-1 replication inhibition. (NCI)
A synthetic, aromatic derivative with anti-estrogenic properties. Similar to the agent raloxifene, arzoxifene binds to and interacts with estrogen receptors as a mixed estrogen agonist/antagonist. This agent exhibits greater bioavailability and higher anti-estrogenic potency in the breast than does raloxifene; it exhibits reduced estrogenicity in the uterus compared with either tamoxifen or raloxifene. Arzoxifene may have beneficial effects on bone and the cardiovascular system (NCI04)
A microsomal triglyceride transfer protein (MTP) inhibitor with antihyperlipidemic activity. In an animal model, inhibition of MTP by implitapide reduced both total cholesterol and triglyceride levels and suppressed progression of atherosclerotic lesions.
Complex compounds in which a dumbbell shaped molecule is encircled by a macrocycle. They are named after rota (wheel) and axis (axle). Notation with a prefix is used to indicate the number of interlocked components. They have potential use in NANOTECHNOLOGY. Rotaxanes have been made with CYCLODEXTRINS and CYCLIC ETHERS.
An orally bioavailable second-generation selective apoptotic antineoplastic drug (SAAND) and analog of the nonsteroidal anti-inflammatory drug (NSAID) sulindac, with potential pro-apoptotic and antineoplastic activities. Upon administration, CP-461 specifically binds to and blocks the activity of cyclic guanosine monophosphate-phosphodiesterase (cGMP-PDE), an enzyme that inhibits the normal apoptosis signal pathway. Inhibition of cGMP-PDE permits the apoptotic signal pathway to proceed unopposed, resulting in apoptotic cell death. cGMP-PDE is overexpressed in a variety of cancer cell types; therefore, CP-461 selectively induces apoptosis in cancer cells, with minimal or no effect in healthy cells.
A HYDROXYMETHYLGLUTARYL-COA-REDUCTASE INHIBITOR, or statin, that reduces the plasma concentrations of LDL-CHOLESTEROL; APOLIPOPROTEIN B, and TRIGLYCERIDES while increasing HDL-CHOLESTEROL levels in patients with HYPERCHOLESTEROLEMIA and those at risk for CARDIOVASCULAR DISEASES.
A novel statin that induces plaque regression and elevates HDL-cholesterol levels.
A benign or malignant neoplasm that arises in the area of the nipple.
Infection in the abdominal cavity resulting from injury, acute intestinal inflammation (e.g., acute appendicitis), intestinal perforation, or complication of abdominal surgery.
An acute or chronic infectious process affecting the liver.
Infection at the site of needle puncture or intravenous catheter placement due to poor aseptic techniques. It is characterized by erythema, pain, swelling, and induration at the catheter insertion site.
Any problem with a feeding tube or its site of insertion.
An overwhelming, irrational, and persistent fear of operating a motor vehicle.
Any disorder occurring postoperatively as a consequence of a thoracic procedure.
A carcinoma of the larynx that arises from the epiglottis.
A teratoma that arises within the myocardium or cardiac chambers.
A cerebrovascular accident (stroke) that occurs because of thromboembolism.
A small round cell tumor with neural differentiation arising from the soft tissues.
A hepatocellular carcinoma that is not amenable to surgical resection.
Migraine associated with an ischemic brain lesion.
Des-gamma carboxyprothrombin (DCP) or pro-thrombin induced by vitamin K absence-II (PIVKA-II) is an abnormal prothrombin protein that is increased in the serum of patients with HCC. Generation of DCP is thought to be a result of an acquired defect in the post- translational carboxylation of the prothrombin precursor in malignant cells.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the esophagus. It is characterized by the presence of malignant small cells.
Bleeding originating from the mediastinum.
An aggressive and progressive mast cell neoplasm characterized by systemic infiltration of internal organs by aggregates of neoplastic mast cells. There is no evidence of mast cell leukemia or clonal hematologic malignancy. Clinical symptoms include hepatomegaly, splenomegaly, portal hypertension, malabsorption syndrome, and pathologic fractures.
An abscess that is located in the parathyroid gland(s).
A serrated polypoid lesion that arises in the colon and rectum. It is usually found in the distant colon and it rarely produces symptoms. This group includes goblet cell rich, mucin poor, and microvesicular hyperplastic polyps.
A usually polypoid neoplasm that arises from the glandular epithelium of the colonic mucosa. It is characterized by a tubular architectural pattern. The neoplastic glandular cells have dysplastic features.
An inflammatory process affecting the salivary duct.
An abscess resulting from infection by Mycobacterium tuberculosis.
The presence of gas within the wall of the large or small intestine.
Pemphigus is a group of chronic autoimmune skin diseases characterised by blisters formation on the outer layer of the skin and the mucous membranes. Three clinical forms have been characterised, of which paraneoplastic pemphigus is extremely rare.
Sexual dysfunction characterized by a delay in climax.
Gastritis that is associated with the presence of granulomas.
Elevation of the voltage (height) of the QRS complex. There are several criteria in use, but the most common is the Sokolov-Lyon criterion (S wave depth in V1 + tallest R wave height in V5-V6 greater than 35 mm).
A type of cataract that forms deep in the central zone (nucleus) of the lens. Nuclear cataracts are usually associated with aging.
Inflammation of the urethra secondary to infection with any bacteria other than Neisseria gonorrhoeae.
An acute or chronic infectious process affecting the stomach.
A rare lymphoma that arises from the liver and the bulk of the tumor is located in the liver. The most frequent types of lymphoma that arise from the liver are diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma.
A neoplasm that arises from the glandular epithelium of the colonic mucosa. It is characterized by tubular and villous architectural patterns. The neoplastic glandular cells have dysplastic features.
A type of cataract affecting the anterior pole of lens immediately adjacent to ('beneath') the lens capsule.
An infectious process originating from an implanted vascular device.
Illnesses that exist and/or were observed in a patient at the time the patient received vaccination.
The aromatic root of the perennial herb Panax quinquefolius, native to eastern North America. American ginseng, used in Chinese traditional medicine and available as a nutritional supplement, is classified as an adaptogenic herb with multiple effects, many of which are regulatory in nature. It contains a complex mixture of saponin glycosides, also known as ginsenosides or panaxosides. Although the mechanism of action is unclear, this agent is reported to enhance the immune system and reduce fatigue.
An orally active nonpeptide renin inhibitor with antihypertensive activity. Aliskiren selectively binds to the S3 sub-pocket of renin, an enzyme in the renin-angiotensin-aldosterone system (RAAS) that is responsible for converting angiotensinogen to angiotensin I (AT I). By inhibiting the activity of renin, the conversion to AT I is prevented, which in turn prevents the conversion of AT I to AT II. This prevents arterial vasoconstriction by AT II and inhibits the production of aldosterone by AT II. As aldosterone causes re-uptake of sodium and water and eventually an increase in extracellular volume, aliskiren is able to prevent the effects that contribute to an increase in blood pressure.
A recombinant, humanized monoclonal antibody directed against CD22, a cell surface glycoprotein present on mature B-cells and on many types of malignant B-cells. After binding to CD22, epratuzumab's predominant antitumor activity appears to be mediated through antibody-dependent cellular cytotoxicity (ADCC).
A spermicidal contraceptive vaginal gel that contains nonoxynol-9 (N-9), available without prescription
An orally bioavailable 4-anilinoquinazoline. Vandetanib selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2), thereby blocking VEGF-stimulated endothelial cell proliferation and migration and reducing tumor vessel permeability. This agent also blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that mediates tumor cell proliferation and migration and angiogenesis.
A humanized monoclonal antibody that binds specifically to TNF-ALPHA and blocks its interaction with endogenous TNF RECEPTORS to modulate INFLAMMATION. It is used in the treatment of RHEUMATOID ARTHRITIS; PSORIATIC ARTHRITIS; CROHN'S DISEASE and ULCERATIVE COLITIS.
A water-soluble phosphate prodrug of N-acetylcolchinol with potential antiangiogenesis and antineoplastic activities. ZD-6126 is converted in vivo into N-acetylcolchinol. N-acetylcolchinol binds to and destabilizes the tubulin cytoskeleton of endothelial cells in tumor blood vessels, which may result in tumor endothelial cell apoptosis, the selective occlusion of tumor blood vessels, cessation of tumor blood flow, and tumor necrosis.
A humanized monoclonal antibody directed against 1D10, a polymorphic determinant on the HLA-DR beta chain that is expressed on normal and neoplastic B cells. Apolizumab induces complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and apoptosis of 1D10 antigen-positive B cells in vitro. (NCI04)
A selective tyrosine kinase inhibitor for the EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) that is used for the treatment of locally advanced or metastatic NON-SMALL CELL LUNG CANCER.
An herbal extract derived from the root of the plant Angelica sinensis with possible antiinflammatory, antispasmodic, vasodilatory, estrogenic, and antitumor activities. Angelica sinensis contains volatile oils, including safrole, isosafrole, and n-butylphthalide; coumarin derivatives, including psoralens, bergapten, osthol, imperatorin, and oxypeucedanin; and ferulic acid. The coumarin derivatives in this agent may vasodilate and relax smooth muscle and may exhibit additive anticoagulant effects. Ferulic acid, a phenolic phytochemical present in plant cell walls, may neutralize free radicals such as reactive oxygen species.In addition, Angelica sinensis extract has been shown to inhibit the growth and induce apoptosis of glioblastoma mutltiforme brain tumor cells through p53-dependent and p53-independent pathways. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=467927&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=467927&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C60817"" NCI Thesaurus)
The sodium salt of a mixture of oligomers formed by ether and ester linkages of up to eight porphyrin units with photodynamic activity. Absorbed selectively by tumor cells, porfimer produces oxygen radicals after activation by 630 nm wavelength laser light, resulting in tumor cell cytotoxicity. In addition, tumor cell death may occur due to ischemic necrosis secondary to vascular occlusion that appears to be partly mediated by the release of thromboxane A2.
A synthetic flavonoid derivative. Idronoxil activates the mitochondrial caspase system, inhibits X-linked inhibitor of apoptosis (XIAP), and disrupts FLICE inhibitory protein (FLIP) expression, resulting in tumor cell apoptosis. This agent also inhibits DNA topoisomerase II by stabilizing the cleavable complex, thereby preventing DNA replication and resulting in tumor cell death.
A formulation of the anthracycline antibiotic doxorubicin in which doxorubicin is bound to microscopic beads of activated carbon and iron as a magnetic-targeted carrier (MTC). Doxorubicin, an intercalator and a topoisomerase II inhibitor, prevents DNA replication and ultimately inhibits protein synthesis. This agent also generates oxygen free radicals, resulting in cytotoxic lipid peroxidation of cell membrane lipids. Guided by the placement of a magnet on the body surface overlying a tumor site, the doxorubicin-MTC complex delivers doxorubicin directly to the tumor site, thereby targeting and prolonging the duration of doxorubicin-mediated cytotoxicity to the tumor bed while minimizing systemic toxicity.
A cancer vaccine consisting of a humanized monoclonal antibody that mimics a tumor-associated antigen 791Tgp72 (also known as CD55). Vaccination with this agent may stimulate a host cytotoxic T-cell response against tumor cells expressing CD55, resulting in tumor cell lysis. (NCI04)
A prodrug comprised of the naturally occurring omega-3 fatty acid docosahexaenoic acid (DHA) covalently conjugated to the anti-microtubule agent paclitaxel. Because tumor cells take up DHA, DHA-paclitaxel is delivered directly to tumor tissue, where the paclitaxel moiety binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. Paclitaxel also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). DHA-paclitaxel exhibits improved pharmacokinetic and toxicity profiles when compared to conventional paclitaxel and has demonstrated antineoplastic activity in animal models of cancer. (NCI04)
A recombinant plasmid DNA vaccine encoding epitopes of tyrosinase with potential antineoplastic activity. Synchrotope TA2M vaccine contains a plasmid encoding 2 epitopes, amino acid sequences 207-216 and 1-17 of tyrosinase, a protein frequently expressed by melanoma cells. Vaccination with the TA2M plasmid DNA vaccine may induce the production of anti-tyrosinase antibodies as well as elicit a cytotoxic T-lymphocyte (CTL) response against tyrosinase-expressing tumor cells, resulting in decreased tumor growth.
A radioimmunoconjugate consisting of the humanized CH2 domain-deleted monoclonal antibody CC49 and iodine I 131 with antineoplastic activity. Monoclonal antibody CC49-deltaCH2 targets the tumor-associated glycoprotein 72 (TAG-72) that is expressed by a wide range of human neoplasms including colorectal, gastric, pancreatic, ovarian, endometrial, breast, non-small cell lung, and prostate cancers. Iodine I 131 monoclonal antibody CC49-deltaCH2 binds to tumor cells expressing TAG-72, selectively delivering a cytotoxic dose of beta and gamma radiation.
A humanized monoclonal antibody (MoAb) against the external domain of the Prostate-specific membrane antigen (PSMA), overexpressed in the malignant prostate and its metastases. Although PSMA is not a biomarker of disease progression, over-expression indicates an aggressive phenotype of the prostate cancer. This humanized J591 (huJ591) MoAb was generated by replacing murine Ig sequences with human ones, thereby MoAb huJ591can be administered to patients on multiple occasions over long time periods without inducing an immune response. Radiolabelled MoAb huJ591 may be used in immunotherapy of prostate cancer.
A finding indicating a deficiency or excess of one or more hormones.
A sulfonyl hydrazine prodrug with antineoplastic activity. VNP40101M alkylates the 06 position of guanine, resulting in DNA crosslinking, strand breaks, chromosomal aberrations, and disruption of DNA synthesis. Intracellular metabolism of this agent also releases methyl isocyanate which inhibits 06-alkyl-guanine transferase, an enzyme involved with DNA repair. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38440&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38440&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2653"" NCI Thesaurus)
A humanized CH2 domain-deleted second-generation monoclonal antibody based on the antibody B72.3 that is directed against tumor-associated glycoprotein 72 (TAG72). TAG72 is expressed by gastric, breast, pancreatic, colorectal, and ovarian carcinoma cells. (NCI04)
A substance being studied in the treatment of oral mucositis (painful mouth sores) caused by cancer therapy and other conditions. Iseganan hydrochloride kills certain bacteria, fungi, and viruses by making holes in their outer membranes and causing them to burst. It is a type of synthetic antimicrobial peptide and a type of synthetic protegrin analog.
An antiserum raised against endotoxins of Escherichia coli J5 strain with potential antibacterial activity. J5 antiserum reacts with lipid A, the key endotoxic component of the lipopolysaccharides (LPS), found mostly in gram-negative bacteria. By binding to endotoxins, J5 antiserum prevents the initiation of a cascade of events in host cells, including the production of pro-inflammatory cytokines that eventually leads to the sepsis syndrome.
A benign or malignant neoplasm affecting the spinal cord during childhood.
A small round cell tumor with neural differentiation arising from the kidney.
A cancer vaccine consisting of an immunogenic peptide derived from the cancer-testis antigen (NY-ESO-1), an antigen found in normal testis and various tumors. Vaccination with NY-ESO-1 peptide vaccine may stimulate the host immune system to mount a humoral and cytotoxic T lymphocyte (CTL) response to cells expressing NY-ESO-1 antigen, resulting in tumor cell lysis.
A radioimmunotherapeutic agent consisting of a murine monoclonal anti-CD20 antibody (ibritumomab) linked by the chelator tiuxetan to the radioisotope yttrium-90 (Y 90). Yttrium Y 90 ibritumomab tiuxetan binds to and specifically delivers beta radiation to CD20-expressing tumor cells, thereby minimizing the systemic effects of radiation.
A cancer vaccine that uses a viral vector system derived from the canarypox virus engineered to target the carcinoembryonic antigen (CEA). It causes infected cells to temporarily display CEA and activates the immune system to attack the tumor cells.
A Chinese herb isolated from the plant Scutellaria barbata D. Don (Lamiaceae) with potential antineoplastic activity. Containing the antioxidant flavone scutellarin, herba Scutellaria barbata has been shown to induce apoptosis of ovarian and breast tumor cells in vitro.
Herbs used in Chinese Herbal Therapy for toxicity attenuation. (NCI)
A radioimmunoconjugate of a murine monoclonal antibody, MoAb Lym-1, labeled with iodine 131 (I-131). MoAb Lym-1 recognizes an epitope of the histocompatibility antigen HLA-DR, which is over-expressed on most B-cell lymphomas. I-131 MoAb Lym-1 delivers beta and gamma radiation emitting I-131 nuclide directly to tumor cells that express HLA-DR, thereby allowing imaging and/or treatment of cancers.
A cancer vaccine comprised of a recombinant fowlpox virus vector encoding the stimulatory molecule transgene B7-1. Recombinant fowlpox-B7.1 vaccine may enhance antigen presentation and activate antitumoral cytotoxic T-cells. (NCI04)
A vaccine comprised of a recombinant fowlpox virus vector encoding a TRIad of COstimulatory Molecules (B7-1, ICAM-1 and LFA-3) (TRICOM), which may enhance antigen presentation and activate cytotoxic T-cells. Fowlpox virus is an attractive vector because its genome is easy to manipulate and it is replication incompetent in mammalian cells. (NCI04)
A heptavalent vaccine consisting of the tumor-associated carbohydrate antigens globohexaosylceramide (globo-H), GM2, Lewis-y, MUC1-32(aa), sTn(c), TF(c), and Tn(c) conjugated with keyhole limpet hemocyanin (KLH), an immunomodulator. This vaccine may induce the production of IgG and IgM antibodies and an antibody-dependent cell-mediated cytotoxicity (ADCC) against tumors expressing these antigens. (NCI04)
A bivalent DNA vaccine encoding epitopes for both Melan-A (MART-1) and tyrosinase with potential antineoplastic activity. Synchrovax SEM plasmid DNA vaccine contains a plasmid pSEM that encodes 4 epitopes: Melan-A (26-35), Melan-A (31-96), tyrosinase (1-9), and tyrosinase (369-377). Both Melan-A and tyrosinase are tumor antigens associated with melanoma. Vaccination with this plasmid DNA vaccine may induce both humoral and cytotoxic lymphocyte (CTL) responses against cells expressing either or both of these antigens, resulting in decreased tumor growth.
A murine monoclonal antibody directed against of the beta subunit of interleukin-2 receptor (IL-2R), expressed on resting T-lymphocytes, natural killer (NK) cells, and some leukemic cell types. Monoclonal antibody Mik-Beta-1 prevents the binding of IL-2 to IL-2R beta, thereby inhibiting the IL-2-mediated proliferation and activation of T-cells.
An orally-agent agent with potential antineoplastic activity. S-3304 inhibits matrix metalloproteinases (MMPs), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. (NCI04)
A recombinant vaccinia virus that encodes granulocyte-macrophage colony stimulating factor (GM-CSF). By activating T-cells and macrophages, vaccination with recombinant vaccinia GM-CSF may enhance the host immune system response to poorly immunogenic tumors, resulting in decreased tumor growth. (NCI04)
A cancer vaccine consisting of a recombinant fowlpox virus encoding human prostate-specific antigen (PSA). Administration of this agent may stimulate a cytotoxic T cell response against PSA-expressing tumor cells. Fowlpox virus is an attractive vector because its genome is easy to manipulate and it is replication incompetent in mammalian cells. (NCI04)
A polysaccharide isolated from the cell walls of bacteria, plants, and fungi with immunostimulant and antineoplastic activities. In a solubilized form, beta-glucan binds to a lectin site within complement receptor 3 (CR3) on leukocytes, priming the receptor to trigger cytotoxic degranulation of leukocytes when leukocyte CR3 binds to complement 3 (iC3b)-coated tumors. Thus, the attachment of beta-glucan to CR3 of circulating leukocytes simulates leukocytes to kill iC3b-coated tumor cells in the same way as they kill iC3b-coated yeast. (NCI04)
An orally bioavailable antimitotic sulfonamide. ABT- 751 binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of microtubules, thereby preventing tumor cell replication. This agent also disrupts tumor neovascularization, reducing tumor blood flow and so inducing a cytotoxic effect. (NCI04)
A specific melanoma antigen protein derived from a patient (NA17) with cutaneous melanoma metastases. When administered in a vaccine formulation, NA17-A antigen may stimulate a cytotoxic T lymphocyte (CTL) response against tumors that express this antigen, which may result in a reduction in tumor size. The NA17-A antigen is part of the enzyme N-acetyl glucosaminyltransferase V (GnT-V). Approximately half of melanomas have been found to express significant levels of this atypical protein, which is not expressed by normal tissues.
A protein comprised of segments of the extracellular domains of human vascular endothelial growth factor receptors 1 (VEGFR1) and 2 (VEGFR2) fused to the constant region (Fc) of human IgG1. VEGF trap binds to vascular endothelial growth factor (VEGF), a pro-angiogenic growth factor, thereby preventing VEGF from binding to its cell receptors. Disruption of this cell receptor binding results in the inhibition of angiogenesis and metastasis, and tumor regression. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38652&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38652&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2682"" NCI Thesaurus)
A murine IgG2a monoclonal antibody directed against a 48 kDa antigen expressed on the cell surface of normal and malignant gastrointestinal epithelium. MoAb D6.12 has been shown to induce antibody-dependent cell-mediated cytotoxicity (ADCC). This MoAb, either alone or in combination with other immunotherapeutic agents, may have possible diagnostic or therapeutic applications in gastrointestinal cancers.
A human IgM monoclonal antibody (MoAb) directed against a human Cytomegalovirus (CMV) antigen. MoAb C-58 recognizes the p51 protein of viral capsid, thereby this agent might be used for the early detection or treatment of CMV infection.
A synthetic 24-mer oligonucleotide containing 3 CpG motifs with potential antineoplastic and immunostimulatory activity. CpG 7909 selectively targets Toll-like receptor 9 (TLR9), thereby activating dendritic and B cells and stimulating cytotoxic T cell and antibody responses against tumor cells bearing tumor antigens. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38660&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38660&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C28580"" NCI Thesaurus)
An injectable formulation of yttrium Y 90 consisting of glass microspheres containing the radioisotope yttrium Y 90. When injected into the tumor vascular bed, yttrium Y 90 glass microspheres occlude tumor blood vessels and deliver a cytotoxic dose of beta radiation to the tumor site, thereby reducing the tumor burden. (NCI04)
A group of agents that bind to endothelin receptors, thereby inhibiting the actions of endothelins. Inhibition of endothelins may decrease tumor growth, progression, and angiogenesis. (NCI04)
A cancer vaccine adjuvant consisting of a recombinant fowlpox virus encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF binds to specific cell surface receptors on various immuno-hematopoietic cell types, enhancing their proliferation and differentiation and stimulating macrophage and dendritic cell functions in antigen presentation and antitumor cell-mediated immunity. Administration of recombinant fowlpox GM-CSF vaccine adjuvant may induce an immune response against tumor cells. Fowlpox virus is an attractive vector because its genome is easy to manipulate and it is replication incompetent in mammalian cells.
A water-soluble camptothecin derivative conjugated to a carbohydrate moiety exhibiting antineoplastic activity. BAY 56-3722 stabilizes the topoisomerase I-DNA covalent complex and forms an enzyme-drug-DNA ternary complex. As a consequence of the formation of this complex, both the initial cleavage reaction and religation steps are inhibited and subsequent collision of the replication fork with the cleaved strand of DNA results in inhibition of DNA replication, double strand DNA breakage and triggering of apoptosis. The peptide carbohydrate moiety of this agent stabilizes the lactone form of camptothecin in blood.
A synthetic nonapeptide derived from a melanoma-associated antigen. Vaccination with MAGE-10.A2 may stimulate a host cytotoxic T-cell response against tumor cells that express the melanoma-associated antigen, resulting in tumor cell lysis. (NCI04)
A tumor vaccine comprised of ethylchlorformate polymerized tumor protein, obtained by treating tumor cells with ethylchloroformate to produce a tumor-specific immunotherapeutic agent. (NCI)
A neuroattenuated, replication-competent, recombinant herpes simplex virus-1 (HSV-1) with potential oncolytic activity. Upon intracerebral administration, oncolytic HSV-1 G207 preferentially replicates within glioma cells, which may elicit tumor-specific systemic immune and cytotoxic T lymphocyte (CTL) responses in addition to direct cytopathic effects. Derived from wild-type HSV-1 strain F, this agent has been neuroattenuated by deletions in both copies of the gamma34.5 gene, the major determinant of HSV neurovirulence. In addition, the HSV-1 gene UL39, encoding the viral ribonucleotide reductase large subunit infected cell protein 6 (ICP6), has been inactivated through the insertion of the Escherichia coli lacZ gene. By inactivating UL39, viral ribonucleotide reductase activity is disrupted, resulting in the inhibition of nucleotide metabolism and viral DNA synthesis in nondividing cells but not in dividing cells.
An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST.
Many people with chronic cancer-related pain experience intermittent flares of pain that can occur even though a person is taking analgesic medications on a fixed schedule for pain control. These severe flares of pain are called breakthrough pain because the pain ""breaks through"" the regular pain medication.
An enteric-coated formulation of ixabepilone, a semisynthetic analogue of epothilone B and a non-taxane tubulin inhibitor, with antineoplastic activity. Ixabepilone binds to and stabilizes tubulin molecules, thereby interfering with the dynamics of microtubule assembly/disassembly. This results in cell cycle arrest at the G2-M phase and leads to apoptosis within fast growing tumor cells. This agent demonstrates antineoplastic activity against taxane-resistant cell lines. Compared to intravenously administered ixabepilone, the oral formulation provides a more manageable way to administer this agent.
A quinazoline derivative with antineoplastic properties. Competing with adenosine triphosphate, erlotinib reversibly binds to the intracellular catalytic domain of epidermal growth factor receptor (EGFR) tyrosine kinase, thereby reversibly inhibiting EGFR phosphorylation and blocking the signal transduction events and tumorigenic effects associated with EGFR activation.
Localized primary tumor, as defined for stage 1, 2A, or 2B, with dissemination limited to skin, liver, and/or bone marrow (limited to infants younger than 1 year). Marrow involvement should be minimal (i.e., <10% of total nucleated cells identified as malignant by bone biopsy or by bone marrow aspirate). More extensive bone marrow involvement would be considered stage 4 disease. The results of the MIBG scan, if performed, should be negative for disease in the bone marrow. (cancer.gov)
A quinolone derivative with potential antineoplastic activity. Semaxanib reversibly inhibits ATP binding to the tyrosine kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2), which may inhibit VEGF-stimulated endothelial cell migration and proliferation and reduce the tumor microvasculature. This agent also inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit, often expressed in acute myelogenous leukemia cells.
Acute muscle weakness and paralysis that develops in critically ill patients who have been treated with multiple drugs during their intensive care unit stay. It is associated with delayed weaning from mechanical ventilation and prolonged rehabilitation.
Heart failure caused by abnormal myocardial contraction during SYSTOLE leading to defective cardiac emptying.
Heart failure caused by abnormal myocardial relaxation during DIASTOLE leading to defective cardiac filling.
An acute episode of worsening pulmonary symptoms related to cystic fibrosis.
A recombinant human deoxyribonuclease I (rhDNAse) with selective DNA cleaving activity. Upon intrapleural administration, dornase alfa catalyzes the degradation of extracellular DNA in airway secretions, which can reduce their viscosity. Thus, dornase alfa may both promote the clearing of airway mucus and improve pulmonary function.
An acute, transmissible, infectious disease associated with high MORTALITY and MORBIDITY in young turkeys (poults). It is characterized by DIARRHEA; ANOREXIA; growth depression, and immune dysfunction. The cause is unknown but astroviruses (AVASTROVIRUS) and coronaviruses (CORONAVIRUS, TURKEY) have been isolated from diseased poults and are thought to cause the enteritis and increased susceptibility to bacterial infections.
HERPES ZOSTER but without eruption of vesicles. Patients exhibit the characteristic pain minus the skin rash, sometimes making diagnosis difficult.
A diverse group of pregnancy-related tumors characterized by excessive proliferation of trophoblasts. Representative examples include hydatidiform mole, gestational choriocarcinoma, and placental site trophoblastic tumor.
A systemic infection of various salmonid and a few nonsalmonid fishes caused by Viral hemorrhagic septicemia virus (see NOVIRHABDOVIRUS),
A highly malignant CHORIOCARCINOMA derived from the non-placental origin such as the totipotent cells in the TESTIS, the OVARY, and the PINEAL GLAND. It produces high levels of CHORIONIC GONADOTROPIN and can metastasize widely through the bloodstream to the lungs, brain, liver, bone, and other viscera by the time of diagnosis.
A transmissible spongiform encephalopathy (prion disease) of DEER and elk characterized by chronic weight loss leading to death. It is thought to spread by direct contact between animals or through environmental contamination with the prion protein (PRIONS).
A class of compounds isolated from the myxobacterium Sorangium cellulosum. Similar to taxanes, epothilone compounds induce microtubule polymerization and stabilize microtubules against depolymerization conditions, thereby inhibiting mitosis. (NCI)
A form of mastocytosis characterized by mast cell infiltration of the skin. (WHO, 2001)
A bilateral vestibular Schwannoma (acoustic neurinoma).
An abnormal laboratory test result indicating the presence of monoclonal immunoglobulins in the blood or urine.
A condition characterized by a broad range of progressive disorders ranging from TENOSYNOVITIS to tendon rupture with or without hindfoot collapse to a fixed, rigid, FLATFOOT deformity. Pathologic changes can involve associated tendons, ligaments, joint structures of the ANKLE, hindfoot, and midfoot. Posterior tibial tendon dysfunction is the most common cause of acquired flatfoot deformity in adults.
The property of the T-CELL RECEPTOR which enables it to react with some antigens and not others. The specificity is derived from the structure of the receptor's variable region which has the ability to recognize certain antigens in conjunction with the MAJOR HISTOCOMPATIBILITY COMPLEX molecule.
A condition characterized by a series of interrelated digital symptoms and joint changes of the lesser digits and METATARSOPHALANGEAL JOINTS of the FOOT. The syndrome can include some or all of the following conditions: hammer toe, claw toe, mallet toe, overlapping fifth toe, curly toe, EXOSTOSIS; HYPEROSTOSIS; interdigital heloma, or contracted toe.
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Antigenic variation as the pathogen passes through an entire host population rather than just a single host.
A polypeptide hormone isolated from the equine placenta. In animals, the activity of pregnant mare serum gonadotropin is similar to that of follicle-stimulating hormone; in humans, this agent is relatively ineffective. This agent is used in veterinary medicine to stimulate ovulation. (NCI04)
A class of genetic disorders resulting in INTELLECTUAL DISABILITY that is associated either with mutations of GENES located on the X CHROMOSOME or aberrations in the structure of the X chromosome (SEX CHROMOSOME ABERRATIONS).
Generically, any agent that destroys microbes. However, usage of the term is increasingly being confined to agents that prevent or reduce the transmission of SEXUALLY TRANSMITTED DISEASES.
Generically, any topical agent that destroys microbes. However, usage of the term is increasingly being confined to topical agents that prevent or reduce the transmission of SEXUALLY TRANSMITTED DISEASES.
A class of non-sedating drugs that bind to but do not activate histamine receptors (DRUG INVERSE AGONISM), thereby blocking the actions of histamine or histamine agonists. These antihistamines represent a heterogenous group of compounds with differing chemical structures, adverse effects, distribution, and metabolism. Compared to the early (first generation) antihistamines, these non-sedating antihistamines have greater receptor specificity, lower penetration of BLOOD-BRAIN BARRIER, and are less likely to cause drowsiness or psychomotor impairment.
A type of COUMARINS with added pyran ring(s).
COUMARINS with two added pyran rings. Some are found in the CALOPHYLLUM genus of plants.
Defective metabolism leading to fat maldistribution in patients infected with HIV. The etiology appears to be multifactorial and probably involves some combination of infection-induced alterations in metabolism, direct effects of antiretroviral therapy, and patient-related factors.
Infections with BACTERIA of the order Bifidobacteriales. This includes infections in the genera BIFIDOBACTERIUM and GARDNERELLA, in the family Bifidobacteriaceae.
A long-acting pegylated form of a recombinant therapeutic agent which is chemically identical to or similar to an endogenous human granulocyte colony-stimulating factor (G-CSF). Produced endogenously by monocytes, fibroblasts, and endothelial cells, G-CSF binds to and activates specific cell surface receptors, stimulating neutrophil progenitor proliferation and differentiation and selected neutrophil functions. Conjugation of the cytokine with a branched polyethylene glycol molecule (pegylation) significantly increases its therapeutic half-life. (NCI04)
A novel oxime derivative of radicicol that destabilizes the hsp90 client proteins, such as erbB2, raf-1 and AKT, which are essential for tumor cell growth and survival. (NCI)
A novel palladium-substituted bacteriochlorophyll derivative and photosensitizer with potential antitumor activity. Upon administration, inactive palladium-bacteriopheophorbide is activated locally when the tumor bed is exposed to photoirradiation; the activated form induces local cytotoxic processes, resulting in local tissue damage, disruption of tumor vasculature, and tumor hypoxia and necrosis.
A synthetic psoralen, light-activated DNA and RNA crosslinking agent, with protective activity against pathogens such as bacteria, viruses, protozoa, and leukocytes. Prior to administration amotosalen is added to plasma and platelets, then in vivo this agent penetrates pathogens and targets DNA and RNA. Upon activation by ultraviolet A light, this agent is able to form interstrand DNA and RNA crosslinks and prevents replication. Inactivation of leukocytes can prevent graft versus host disease upon transfusion.
A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE with D-tryptophan substitution at residue 6.
Splitting of the RETINA into two layers at the level of the outer plexiform layer, beginning as a cystic degeneration in the extreme retinal periphery. It usually occurs after 40 years of age and is generally not progressive.
A botanical formulation with potential chemopreventive activities. Sho-Saiko-to, an herbal mixture, contains seven herbal extracts whose mechanism of action if not fully understood. There is evidence of antiproliferative effects against hepatocellular carcinoma in vitro. Other effects of this agent described in animal models include the prevention of liver injury and hepatocyte-regenerating activity. Antitumor effects associated with this herbal product may include induction of apoptosis, cell cycle arrest at the G0/G1 phase, and activation of an immune response, characterized by the release of cytokines as well as activation of effector cells, such as macrophages and natural killer cells.
A pyrazinecarboxamide derivative with activity against RNA viruses. Favipiravir is converted to the ribofuranosyltriphosphate derivative by host enzymes and selectively inhibits the influenza viral RNA-dependent RNA polymerase.
The hydrochloride salt of xaliproden, an orally-active, synthetic, non-peptidic 5-hydroxytryptamine (5-HT) 1A receptor agonist with neurotrophic and neuroprotective activities. Although its mechanism of action is not fully understood, xaliproden appears to either mimic the effects of neurotrophins or stimulate their synthesis, thereby stimulating neuronal cell differentiation and proliferation and inhibiting neuronal cell death. The neuroprotective effect of this agent involves the activation of MAP kinase pathways via stimulation of the 5-HT1A receptor.
Complement activation triggered by the interaction of microbial POLYSACCHARIDES with serum MANNOSE-BINDING LECTIN resulting in the activation of MANNOSE-BINDING PROTEIN-ASSOCIATED SERINE PROTEASES. As in the classical pathway, MASPs cleave COMPLEMENT C4 and COMPLEMENT C2 to form C3 CONVERTASE (C4B2A) and the subsequent C5 CONVERTASE (C4B2A3B) leading to cleavage of COMPLEMENT C5 and assembly of COMPLEMENT MEMBRANE ATTACK COMPLEX.
Genetic diseases that are linked to gene mutations on the X CHROMOSOME in humans (X CHROMOSOME, HUMAN) or the X CHROMOSOME in other species. Included here are animal models of human X-linked diseases.
The process by which cells convert mechanical stimuli into a chemical response. It can occur in both cells specialized for sensing mechanical cues such as MECHANORECEPTORS, and in parenchymal cells whose primary function is not mechanosensory.
A dietary supplement containing cocoa extract derived from the cacao bean, with potential vasodilating, anti-inflammatory, cardiovascular protective, neuroprotective, cognition enhancing and chemopreventive activities. Cocoa extract contains flavonoids, including high levels of epicatechin, catechin, procyanidins and xanthines, such as theobromine. Upon oral administration, the bioactive ingredients in the cocoa extract inhibit angiotensin-converting enzyme (ACE) and increase the production of nitric oxide (NO) through the activation of endothelial nitric oxide synthase (eNOS). This causes vasodilation, improves blood flow, and decreases blood pressure. The cocoa extract also improves insulin sensitivity, enhances cognition, and decreases the production of pro-inflammatory molecules. In addition, this extract exerts antioxidant effects and is able to scavenge reactive oxygen species (ROS). As a result, healthy cells are protected from oxidative stress and DNA damage.
Ovarian cancer is a disease that affects women. In this form of cancer, certain cells in the ovary become abnormal and multiply uncontrollably to form a tumor. The ovaries are the female reproductive organs in which egg cells are produced. In about 90 percent of cases, ovarian cancer occurs after age 40, and most cases occur after age 60.The most common form of ovarian cancer begins in epithelial cells, which are the cells that line the surfaces and cavities of the body. These cancers can arise in the epithelial cells on the surface of the ovary. However, researchers suggest that many or even most ovarian cancers begin in epithelial cells on the fringes (fimbriae) at the end of one of the fallopian tubes, and the cancerous cells migrate to the ovary.Cancer can also begin in epithelial cells that form the lining of the abdomen (the peritoneum). This form of cancer, called primary peritoneal cancer, resembles epithelial ovarian cancer in its origin, symptoms, progression, and treatment. Primary peritoneal cancer often spreads to the ovaries. It can also occur even if the ovaries have been removed. Because cancers that begin in the ovaries, fallopian tubes, and peritoneum are so similar and spread easily from one of these structures to the others, they are often difficult to distinguish. These cancers are so closely related that they are generally considered collectively by experts.In about 10 percent of cases, ovarian cancer develops not in epithelial cells but in germ cells, which are precursors to egg cells, or in hormone-producing ovarian cells called granulosa cells.In its early stages, ovarian cancer usually does not cause noticeable symptoms. As the cancer progresses, signs and symptoms can include pain or a feeling of heaviness in the pelvis or lower abdomen, bloating, feeling full quickly when eating, back pain, vaginal bleeding between menstrual periods or after menopause, or changes in urinary or bowel habits. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a woman has ovarian cancer.In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If ovarian cancer spreads, cancerous tumors most often appear in the abdominal cavity or on the surfaces of nearby organs such as the bladder or colon. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.Some ovarian cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary ovarian cancers tend to develop earlier in life than non-inherited (sporadic) cases.Because it is often diagnosed at a late stage, ovarian cancer can be difficult to treat; it leads to the deaths of about 14,000 women annually in the United States, more than any other gynecological cancer. However, when it is diagnosed and treated early, the 5-year survival rate is high.
A sialoglycoprotein hormone secreted by the placenta and maintains the corpus luteum at the beginning of the gestation period.
A finding indicating an increased density of minerals in the bones. Causes include osteopetrosis and Paget disease.
Stage IV includes: Any T, Any N, M1, Any G, Tumor location: Any. M1: Distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
A finding of increased space between the intersections of a newborn's cranial bones.
Uncoordinated or ineffective drawing of saliva or breast milk by a newborn infant.
An uncommon complication of INTRAMUSCULAR INJECTION leading to variable degrees of necrosis of skin and underlying tissue.
Elevation in the concentration of albumin in the blood.
An infectious process affecting the small and large intestines. Symptoms include diarrhea, cramping abdominal pain, and fever.
A decreased concentration of carnitine in the blood.
An abnormal growth in the small or large intestine.
Brugada syndrome is characterized by cardiac conduction abnormalities (ST-segment abnormalities in leads V1-V3 on ECG and a high risk for ventricular arrhythmias) that can result in sudden death. Brugada syndrome presents primarily during adulthood although age at diagnosis may range from infancy to late adulthood. The mean age of sudden death is approximately 40 years. Clinical presentations may also include sudden infant death syndrome (SIDS; death of a child during the first year of life without an identifiable cause) and the sudden unexpected nocturnal death syndrome (SUNDS), a typical presentation in individuals from Southeast Asia. Other conduction defects can include first-degree AV block, intraventricular conduction delay, right bundle branch block, and sick sinus syndrome.
The presence of a thrombus within a vascular shunt.
An infection that is caused by Orbivirus.
A painful restriction of joint motion due to post-traumatic excessive scarring.
Accumulation of cell free, noninflammatony fluid within the wall of the intestinal tract producing uniform thickening of the mucosal folds.
An acute inflammatory disorder of the colon secondary to infection with any species of the bacterial genus Clostridium. Symptoms include acute diarrhea, abdominal pain, and myalgia.
Brown or black discoloration of the nails.
A benign ovarian cyst that develops and regresses during the menstrual cycle as part of normal ovarian function.
Movements, behaviors and sensations similar to a seizure, but due to psychological distress instead of a neurological disorder.
A syndrome of emergence or increment of neuropsychiatric symptoms, such as confusion and behavioral disturbances, in the late afternoon, early evening or at night.
A problem with a central venous access catheter or site of insertion.
Leakage of contents from the intestinal stoma.
A papillomatous lesion that arises from the eyelid. The representative example is eyelid squamous cell papilloma.
Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.
Pneumonia that is caused by Staphylococcus aureus and is resistant to methicillin treatment.
Endocarditis affecting a native valve of the heart.
An electrocardiographic finding in which there is an alternating pattern of any of the waveform components.
A cyclic lipopeptide echinocandin derivative with antifungal activity. Anidulafungin inhibits 1,3 beta-D-glucan synthase, an enzyme involved in fungal cell wall synthesis, resulting in cell lysis and death. This agent is active against Candida species and Aspergillus. (NCI04)
An inactive agent that is used as a negative control for the inhibition of epidermal growth factor receptor tyrosine kinase activity. (NCI)
A pyrazole and piperidine derivative that acts as a selective cannabinoid type-1 receptor (CB1 RECEPTOR) antagonist. It inhibits the proliferation and maturation of ADIPOCYTES, improves lipid and glucose metabolism, and regulates food intake and energy balance. It is used in the management of OBESITY.
An orally administered third generation platinum compound with potential antineoplastic activity. Satraplatin forms highly reactive, charged, platinum complexes which bind to nucleophilic groups in DNA, inducing intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links. These cross-links result in cell growth inhibition and apoptosis.
An azetidine derivative and ANTICHOLESTEREMIC AGENT that inhibits intestinal STEROL absorption. It is used to reduce total CHOLESTEROL; LDL CHOLESTEROL, and APOLIPOPROTEINS B in the treatment of HYPERLIPIDEMIAS.
A 20-mer antisense oligonucleotide complementary to a coding region in the mRNA of the R2 small subunit component of human ribonucleotide reductase. GTI-2040 decreases mRNA and protein levels of R2 in vitro and may inhibit tumor cell proliferation in human tumors in vivo. (NCI04)
A piperazinyl quinazoline receptor tyrosine kinase inhibitor with antineoplastic activity. Tandutinib inhibits the autophosphorylation of FLT3 (FMS-Like Tyrosine kinase-3), c-KIT and PDGF (platelet-derived growth factor) receptor tyrosine kinases, thereby inhibiting cellular proliferation and inducing apoptosis.
A cytokine-peptide conjugate composed of the cytokine tumor necrosis factor alpha (TNF-alpha) chemically linked to the peptide CNGRC. The peptide moiety CNGRC, a ligand for the membrane-bound metalloprotease CD13, binds to endothelial cells of the angiogenic vasculature that express CD13 (also known as aminopeptidase N); subsequently, the TNF-alpha moiety induces apoptosis in endothelial cells expressing CD13, thereby inhibiting tumor-associated angiogenesis. (NCI05)
A synthetic peptide corresponding to the first 11 N-terminal amino acids of human lactoferrin (hLF1-11) with potential antimicrobial activity. Human lactoferrin, a 692 amino acid glycoprotein belonging to the transferrin family of metal-binding proteins, can be found in milk and other secretory fluids as well as in polymorphonuclear cells and leukocytes. Human lactoferrin plays a role in the innate defense of mucosal surfaces and neutrophils. Although the exact mechanism through which this peptide exerts its effect has yet to be fully elucidated, hLF1-11 may seize iron, thereby limiting the availability of free iron for microorganisms in the body. hLF1-11 appears to be effective against a variety of bacteria and fungi, including the multidrug-resistant Acinetobacter baumannii, multidrug-resistant Staphylococcus aureus, and fluconazole-resistant Candida albicans strains.
A phthalimide and piperidone derivative that has immunomodulatory and antiangiogenic properties. It is used for the treatment of transfusion-dependent anemia in MYELODYSPLASTIC SYNDROMES, and for the treatment of MULTIPLE MYELOMA, and relapsed or refractory MANTLE CELL LYMPHOMA.
Peptides that regulate the WATER-ELECTROLYTE BALANCE in the body, also known as natriuretic peptide hormones. Several have been sequenced (ATRIAL NATRIURETIC FACTOR; BRAIN NATRIURETIC PEPTIDE; C-TYPE NATRIURETIC PEPTIDE).
Diseases of the parasympathetic or sympathetic divisions of the AUTONOMIC NERVOUS SYSTEM; which has components located in the CENTRAL NERVOUS SYSTEM and PERIPHERAL NERVOUS SYSTEM. Autonomic dysfunction may be associated with HYPOTHALAMIC DISEASES; BRAIN STEM disorders; SPINAL CORD DISEASES; and PERIPHERAL NERVOUS SYSTEM DISEASES. Manifestations include impairments of vegetative functions including the maintenance of BLOOD PRESSURE; HEART RATE; pupil function; SWEATING; REPRODUCTIVE AND URINARY PHYSIOLOGY; and DIGESTION.
The citrate salt of piperazine, a cyclic amine with anthelminthic property. Piperazine citrate is a gamma-aminobutyric acid GABA receptor agonist and blocks the activity of acetylcholine at the neuromuscular junction thereby altering neuronal cell membrane permeability and causing hyperpolarization. This results in flaccid paralysis of worm musculature allowing the worm to become dislodged by peristalsis and expelled from the body.
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
An aza-dipeptide analogue with a bis-aryl substituent on the (hydroxethyl)hydrazine moiety with activity against both wild type and mutant forms of HIV protease. Atazanavir does not elevate serum lipids, a common problem with other protease inhibitors.
The state or condition of being living or deceased; also includes the case where the vital status is unknown.
The result of observation and overall assessment of a subject's outward aspect including appearance and movements; for example, in a human newborn general appearance includes skin color and tone, range of motion, and spontaneous movements.
Complete sensorineural hearing loss which develops suddenly over a period of hours or a few days.
A pathological condition characterized by the presence of a number of GASTRIC DIVERTICULA in the STOMACH.
Antigen Binding Interaction involves specific and high affinity non-covalent interaction (binding) of an endogenous antibody through intermolecular physical forces of attraction and spatial complementarity with a soluble or particulate substance (antigen) that induces an immune response.
Heparin Binding involves a biophysical interaction between a biological molecule, such as a protein, and heparin, a sulfated glycosaminoglycan of mixed polysaccharide nature, varying in molecular weight, and released by mast cells and basophils in many tissues. Lipotrophic by activation of lipoprotein lipase, anticoagulant heparin also binds to and enhances antithrombin III activity and inhibits several coagulation factors.
Hyaluronic Acid Binding involves a biophysical interaction between a biological molecule, such as a protein, and hyaluronic acid, a linear glycosaminoglycan of repeating disaccharide units, in proteoglycans.
Lipid Binding is the molecular interaction between a lipid molecule and a macromolecule (usually protein) for transport, catalysis, localization, or modification of function.
Phospholipid Interaction involves the molecular interaction between a phospholipid molecule and a macromolecule (usually protein) for transport, catalysis, localization, or modification of function.
GTP Binding is a molecular interaction between specific proteins (containing a GTP binding site) and guanosine 5-prime triphosphate during diverse cellular processes, such as RNA synthesis, translation, signal transduction, and cytoskeletal assembly.
Growth Factor Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction and often spatial complementarity with extracellular signaling molecules (ligands) involved in the control of target cell proliferation, survival, and differentiation.
The action characteristic of a hormone, any substance formed in very small amounts in one specialized organ or group of cells and carried (sometimes in the bloodstream) to another organ or group of cells in the same organism, upon which it has a specific regulatory action. The term was originally applied to agents with a stimulatory physiological action in vertebrate animals (as opposed to a chalone, which has a depressant action). Usage is now extended to regulatory compounds in lower animals and plants, and to synthetic substances having comparable effects; all bind receptors and trigger some biological process. [GOC:dph, GOC:mah, ISBN:0198506732]
A process that involves the binding of an integrin to one of its ligands, including fibronectin, vitronectin, collagen and laminin. These interactions are involved in attachment of the cell to the extracellular matrix and transduction of signals related to cell growth, division, differentiation, survival and apoptosis.
The determination of the amount of total transforming growth factor beta in a biological specimen.
Catalysis of the reaction: sn-glycerol 3-phosphate + a quinone = glycerone phosphate + a quinol. [EC:1.1.5.3]
Enables the facilitated diffusion of a calcium ion (by an energy-independent process) involving passage through a transmembrane aqueous pore or channel without evidence for a carrier-mediated mechanism. [GOC:mtg_transport, GOC:pr, ISBN:0815340729]
An adenocarcinoma arising from the uterine body cavity. This is the most frequent malignant tumor affecting the uterine body, and is linked to estrogen therapy. Most patients present with uterine bleeding and are over age 40 at the time of diagnosis. The prognosis depends on the stage of the tumor, the depth of the uterine wall invasion, and the histologic subtype. Endometrioid adenocarcinoma is the most frequently seen morphologic variant of endometrial adenocarcinoma.
The chemical reactions and physical changes involving a xenobiotic compound, a compound foreign to living organisms. Used of chemical compounds, e. g. a xenobiotic chemical, such as a pesticide. (Gene Ontology)
A part of innate immunity, the Inflammatory Response occurs when injured tissues induce release of vasodilatory, opsonizing, and chemotactic mediators that attract macrophages and leukocytes to phagocytize and destroy foreign substances; dilate local blood vessels increasing local blood flow; increase capillary permeability; produce edematous swelling; and induce pain. Plasma- and cell-derived inflammatory mediators include Prostaglandins, Leukotrines, Cytokines, Lymphokines, Monokines, PAF, Histamine, Bradykinin, Complement, and Interferons.
A series of molecular signals initiated by the binding of an extracellular ligand to a transforming growth factor beta receptor on the surface of a target cell, and ending with regulation of a downstream cellular process, e.g. transcription. [GOC:BHF, GOC:mah, GOC:signaling]
A series of molecular signals initiated by the binding of a member of the BMP (bone morphogenetic protein) family to a receptor on the surface of a target cell, and ending with regulation of a downstream cellular process, e.g. transcription. [GOC:signaling, ISBN:0878932437, PR:000000034]
The hepatocyte growth factor receptor, also called c-Met, is activated by HGF and stimulates proliferation of hepatocytes and other cell types. Mutated forms of the HGF receptor are associated with oncogenesis and metastasis, making the HGF receptor a potential therapeutic target for cancer drugs. Changes in cell motility, cell shape, adhesion, resistance to apoptosis, and anchorage independent growth all contribute to the role of c-Met in cancer. The HGF receptor is a heterodimer with tyrosine kinase activity and associates with a multiprotein complex involved in downstream signal transduction. The HGF receptor can associate with several different signaling systems, including src, Grb2/SOS, PI3 kinase and Gab1. One of the major substrates of the activated HGF receptor tyrosine kinase is the adaptor protein Gab1. Gab1 interacts with Crk and CrkL, two proteins with SH2 and SH3 protein interaction domains that couple to signaling further downstream. The actions of HGF on paxillin, DOCK180, and Rap1, mediated through GAB1 and other members of this complex, alter cell motility. Regulation of Rho, Rac1, and CDC42 pathways in response to HGF all contribute to changes in cellular motility. Another target of the HGF receptor kinase is the focal adhesion kinase, FAK. The activation of FAK induces the formation of focal adhesions, a preliminary step to increased cell motility and tissue invasion by transformed cells, and paxillin phosphorylation may also alter cell adhesion of Met transformed cells. Src and p130cas are required for the role of FAK in HGF induced cellular transformation. HGF also blocks anoikis, the induction of apoptosis through suspension of cells, by acting on Erk and AKT kinases. This activity may contribute to anchorage independent growth of Met transformed cells. Signaling by integrins also plays a key role in the activation of tissue invasive growth by HGF. The alpha6beta4 integrin acts as a cofactor along with Meta to participate in cell growth and proliferation. In addition to altering cell adhesion, proliferation, and cell motility, HGF alters cellular transcription through activation of STAT3. STAT3 activation by HGF is independent of PI3 kinase or map kinases and alters gene expression leading to changes in cellular shape. Although HGF is associated with cellular proliferation and survival, in rat liver epithelial cells HGF induces apoptosis and inhibits cell growth. (This definition may be outdated - see the DesignNote.)
A series of molecular signals initiated by the binding of an extracellular ligand to the receptor Notch on the surface of a target cell, and ending with regulation of a downstream cellular process, e.g. transcription. [GOC:go_curators, GOC:signaling]
A series of molecular signals generated as a consequence of activation of the transmembrane protein Smoothened. [GOC:mah, PMID:15205520]
Post-translational processing of amino acids within a histone protein.
Histone Acetylation involves covalent linkage of acetyl groups to highly basic histone proteins associated with DNA, particularly in active chromatin, and may be involved in regulation of gene expression.
Histone Deacetylation is the covalent post-translational enzymatic addition of an acetyl group(s) to a histone protein. By exposing cationic sites on the protein that promote ionic interaction with the negatively charged DNA backbone, Histone Deacetylation induces DNA condensation and regulates genetic functions, such as transcription. (NCI)
The chemical reactions and pathways involving galactose, the aldohexose galacto-hexose. D-galactose is widely distributed in combined form in plants, animals and microorganisms as a constituent of oligo- and polysaccharides; it also occurs in galactolipids and as its glucoside in lactose and melibiose. [ISBN:0198506732]
The chemical reactions and pathways resulting in the formation of sterols, steroids with one or more hydroxyl groups and a hydrocarbon side-chain in the molecule. [GOC:go_curators]
The chemical reactions and pathways resulting in the formation of lysine, 2,6-diaminohexanoic acid. [GOC:go_curators]
Polyamine Catabolism is a destructive metabolic process in which low molecular weight cations, containing two or more amine groups (polyamines), are converted into excreted compounds.
The chemical reactions and pathways involving tryptophan, the chiral amino acid 2-amino-3-(1H-indol-3-yl)propanoic acid. [ISBN:0198547684]
The chemical reactions and pathways involving tyrosine, an aromatic amino acid, 2-amino-3-(4-hydroxyphenyl)propanoic acid. [GOC:go_curators]
The chemical reactions and pathways involving D-alanine, the D-enantiomer of the amino acid alanine, i.e. (2R)-2-aminopropanoic acid. [CHEBI:15570, GOC:ai, GOC:jsg]
The chemical reactions and pathways involving histidine, 2-amino-3-(1H-imidazol-4-yl)propanoic acid. [GOC:go_curators]
The chemical reactions and pathways involving beta-alanine (3-aminopropanoic acid), an achiral amino acid and an isomer of alanine. It occurs free (e.g. in brain) and in combination (e.g. in pantothenate) but it is not a constituent of proteins. [GOC:jl, ISBN:0198506732]
Keratan sulfate (KS) is a glycosaminoglycan with the basic disaccharide unit of N-acetyllactosamine, Gal(b1-4)GlcNAc(b1-3), with sulfate esters at C-6 of GlcNAc and Gal residues. There are two types of KS distinguished by the protein linkage: type I for N-linked via the N-glycan core structure and type II for O-linked via the O-glycan core 2 structure.
Biogenic Amine Metabolism involves anabolic and catabolic biochemical changes to a type of nitrogen containing hydrocarbons (biogenic amines) involved in signaling as neurotransmitters or hormones or as components of vitamins, phospholipids, or ribosomes within a cell as materials needed for important life processes.
The chemical reactions and pathways resulting in the formation of folic acid, pteroylglutamic acid. [GOC:ai]
Metabolic processes that utilize folic acid (as tetrahydrofolate) as a carbon unit donor.
The chemical reactions and pathways resulting in the formation of lactose, the disaccharide galactopyranosyl-glucose. [GOC:go_curators]
A complex cycle of enzyme-mediated reactions which catalyzes the reduction of carbon dioxide to sugar. As well as carbon dioxide the cycle requires reducing power in the form of reduced nicotinamide adenine dinucleotide phosphate (NADP) and chemical energy in the form of adenosine triphosphate (ATP). The reduced NADP (NADPH) and ATP are produced by the 'light' reactions. [ISBN:0582015952]
The fixation of carbon dioxide (CO2) as glucose in the chloroplasts of C3 plants; uses ATP and NADPH formed in the light reactions of photosynthesis; carbon dioxide reacts with ribulose 1,5-bisphosphate (catalyzed by the function of ribulose-bisphosphate carboxylase) to yield two molecules of 3-phosphoglycerate; these are then phosphorylated by ATP to 1,3-bisphosphateglyceraldehyde which, in turn, is then reduced by NADPH to glyceraldehyde 3-phosphate. The glyceraldehyde 3-phosphate is converted to fructose 5-phosphate and ribulose 5-phosphate by aldolase and other enzymes; the ribulose 5-phosphate is phosphorylated by ATP to ribulose 1,5-bisphosphate. [ISBN:0198547684]
The chemical reactions and pathways resulting in the formation of lipopolysaccharides, any of a group of related, structurally complex components of the outer membrane of Gram-negative bacteria. [GOC:ai, GOC:mr]
The chemical reactions and pathways resulting in the formation of ubiquinone, a lipid-soluble electron-transporting coenzyme. [GOC:mah]
The chemical reactions and pathways resulting in the formation of terpenoids, any member of a class of compounds characterized by an isoprenoid chemical structure. [GOC:ai]
The chemical reactions and pathways resulting in the formation of ceramide oligosaccharides carrying in addition to other sugar residues, one or more sialic acid residues. [ISBN:0198506732]
The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. Choline kinase is the initial enzyme that produces phosphocholine from choline in the sequence and may play a regulatory role. (From LocusLink and NCI)
Bile acids are steroid carboxylic acids derived from cholesterol in vertebrates. The primary bile acids, cholic acid and chenodeoxycholic acid, are synthesized in the liver and conjugated with taurine or glycine before secretion via bile into the intestine. The conversion from cholesterol to cholic and chenodeoxycholic acids involves four steps: 1) the initiation of synthesis by 7alpha-hydroxylation of sterol precursors, 2) further modifications to the ring structures, 3) side-chain oxidation and shortening (cleavage) by three carbons, and 4) conjugation of the bile acid with taurine or glycine.
The enzymatic synthesis of PEPTIDES without an RNA template by processes that do not use the ribosomal apparatus (RIBOSOMES).
Nucleotide Biosynthesis consists of activities of biologic molecules or complexes involved in the enzymatic formation of nucleoside phosphates, the monomeric building blocks from which DNA or RNA polymers are constructed.
The chemical reactions and pathways resulting in the breakdown of glycoproteins, any protein that contains covalently bound glycose (i.e. monosaccharide) residues; the glycose occurs most commonly as oligosaccharide or fairly small polysaccharide but occasionally as monosaccharide. [GOC:go_curators, ISBN:0198506732]
A type of POST-TRANSLATIONAL PROTEIN MODIFICATION by SMALL UBIQUITIN-RELATED MODIFIER PROTEINS (also known as SUMO proteins).
The generation of ubiquitin from proproteins and the processing of polyubiquitin chains to release monomeric ubiquitin. (NCI)
The chemical reactions and pathways involving glutathione, the tripeptide glutamylcysteinylglycine, which acts as a coenzyme for some enzymes and as an antioxidant in the protection of sulfhydryl groups in enzymes and other proteins; it has a specific role in the reduction of hydrogen peroxide (H2O2) and oxidized ascorbate, and it participates in the gamma-glutamyl cycle. [CHEBI:16856, ISBN:0198506732]
Triglyceride Metabolism involves anabolic and catabolic biochemical changes to triglycerides.
The chemical reactions and pathways involving biotin, cis-tetrahydro-2-oxothieno(3,4-d)imidazoline-4-valeric acid; the (+) enantiomer is very widely distributed in cells and serves as a carrier in a number of enzymatic beta-carboxylation reactions. [ISBN:0198506732]
Androgen Metabolism consists of diverse biochemical reactions in the adrenal cortex that produce 19-carbon steroid hormones, which promote male sexual development or convert such steroids to metabolic derivatives.
Estrogen Metabolism consists of diverse biochemical reactions primarily in the ovary that produce 19-carbon steroid hormones, which promote secondary female sexual development and menstrual function or convert such steroids to metabolic derivatives.
The chemical reactions and pathways involving glycerolipids, any lipid with a glycerol backbone. Diacylglycerol and phosphatidate are key lipid intermediates of glycerolipid biosynthesis. [GOC:ai, PMID:8906569]
The chemical reactions and pathways involving globosides, globotetraosylceramides, ceramides containing a core structure of GalNAc-beta-(1->3)-Gal-alpha-(1->4)-Glc(I). Globosides are the major neutral glycosphingolipid in normal kidneys and erythrocytes. [ISBN:0198506732]
Phospholipid Metabolism involves anabolic and catabolic biochemical changes made to phospholipids.
The chemical reactions and pathways involving methane, a colorless, odorless, flammable gas with the formula CH4. It is the simplest of the alkanes. [ISBN:0198506732]
The chemical reactions and pathways involving pyruvate, 2-oxopropanoate. [GOC:go_curators]
The covalent chemical or post-translational biochemical removal of a phosphate group(s) from a peptide or protein, by phosphatases. (NCI)
Protein phosphorylation is one of various post-translational protein modifications that regulates protein function and enzymatic activity. The major phosphoryl acceptors in proteins are serine, threonine, and tyrosine.
Peptide Metabolism involves cellular biotransforming chemical modifications of peptides.
Conformational transitions of a protein from unfolded states (after PROTEIN UNFOLDING) to a more folded state.
A biochemical reaction that covalently attaches nitric oxide to the sulfur atom in an organic thiol.
Post-translational enzymatic covalent addition of a methyl group(s) to a peptide or protein.
The process of targeting specific proteins to particular regions of the cell, typically membrane-bounded subcellular organelles. Usually requires an organelle specific protein sequence motif. [GOC:ma]
The chemical reactions and pathways involving the nonmetallic element sulfur or compounds that contain sulfur, such as the amino acids methionine and cysteine or the tripeptide glutathione. [GOC:ai]
The chemical reactions and pathways involving thiamine (vitamin B1), a water soluble vitamin present in fresh vegetables and meats, especially liver. [CHEBI:18385, GOC:jl, ISBN:0198506732]
The chemical reactions and pathways involving riboflavin (vitamin B2), the precursor for the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). [GOC:jl, http://www.indstate.edu/thcme/mwking/vitamins.html]
Caspase Activation involves induction of the activity of intracellular cysteine endopeptidase family members kept inactive by mitochondrial surface proteins (BcL-2 Family) and involved in initial signaling and downstream proteolytic cleavages (at P1 aspartic acids) in inflammation and apoptotic cell death when signals block BcL-2 function and activators initiate caspase cascades.
The anhydrous form of D-glucose, a natural monosaccharide and carbohydrate. Dextrose serves to replenish lost nutrients and electrolytes. The agent provides metabolic energy and is the primary ingredient in oral rehydration salts (ORS) and is used in intravenous (IV) fluids to provide nutrients to patients under intensive care who are unable to receive them by the oral route. Solutions containing dextrose restore blood glucose levels and provide calories and may aid in minimizing liver glycogen depletion and exerts a protein-sparing action. Dextrose anhydrous also plays a role in the production of proteins and in lipid metabolism.
An extract of the whole plant Viscum album (mistletoe) with potential biological response modifier (BRM) activity. Mistletoe extract may both stimulate the antitumoral functions of the immune system and have a direct toxic effect on tumor cells. (NCI04)
Involves temporary, non-covalent binding of two or more molecules as a result of intermolecular physical forces and often involves spatial complementarity between the interacting objects.
An infection that affects the gastrointestinal system and the abdomen.
Polyneuropathy that is persistent or long-standing in nature.
A laboratory test result indicating abnormally high concentration of hydroxyproline in the urine.
A laboratory test result indicating other than normal parameters after a phenolsulfonphthaliein test.
A laboratory test result indicating normal parameters after a phenolsulfonphthaliein test.
A constellation of features seen in the hyperinsulinemic fetus of a diabetic mother that include macrosomia, postnatal hypoglycemia and polycythemia.
Inflammation of both the PERICARDIUM and the PLEURA.
Stage I includes: (T1, N0, M0); (T2, N0, M0). T1: Tumor invades lamina propria or submucosa. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: IIA (T3, N0, M0); IIB (T4, N0, M0). T3: Tumor invades through the muscularis propria into the subserosa or into the nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less. T4: Tumor perforates the visceral peritoneum or directly invades other organs or structures (including other loops of small intestine, mesentery, or retroperitoneum more than 2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: IIIA (Any T, N1, M0); IIIB (Any T, N2, M0); N1: Metastasis in 1-3 regional lymph nodes. N2: Metastasis in four or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis. (AJCC 7th ed.)
A necrotic process occurring in the gallbladder.
Abnormal permanent enlargement of the lung air spaces distal to terminal bronchiole not resulted from wall destruction, e.g. due to loss of opposite lung.
An abnormally increased level of circulationg alpha-globulin.
Encapsulated collection of lymphatic fluid around a transplanted kidney.
Increased concentration of lactate in the cerebrospinal fluid.
An increase in any of the parameters used to measure the mechanical function of the lungs and associated structures.
Pathological deposition of calcium salts in one or more arteries.
A very rare syndrome characterized by eye abnormalities that lead to vision impairment. These abnormalities include iris atrophy, decreased corneal endothelium, iris nodules, adhesion of the iris to the lens and glaucoma.
A rare disease caused by the human papillomavirus (HPV), most commonly types 6 and 11, that affects tissue along the respiratory tract with the majority of cases affecting the larynx. The disease has a bimodal distribution and manifests in those younger than age 5, juvenile-onset recurrent respiratory papillomatosis (JORRP), and those older than age 40, adult-onset recurrent respiratory papillomatosis (AORRP). JORRP is more common and more severe in presentation than AORRP. In a small percentage of patients, respiratory papillomas may undergo malignant transformation to squamous cell carcinomas that have a poor prognosis.
Stage IVA includes: T4, N0-1, M0. T4: Tumor invades the main portal vein or hepatic artery, or invades two or more extrahepatic organs or structures. N0: No regional lymph node metastasis. N1: Metastases to nodes along the cystic duct, common bile duct, hepatic artery, and/or portal vein. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IVB includes: (Any T, N2, M0); (Any T, Any N, M1). N2: Metastases to periaortic, pericaval, superior mesenteric artery, and/or celiac artery lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (from AJCC 7th Ed.)
Cancer has spread to organs that are near the pancreas (such as the stomach, spleen, or colon) but has not spread to distant organs (such as the liver or lungs).
Stage IVA carcinoma of the liver according to the American Joint Committee on Cancer, 7th and 8th editions.
Cancer of the pancreas in which the cancer has spread to distant organs (such as the liver or lungs).
Stage I includes: IA: (T1, N0, M0); IB: (T2, N0, M0). T1: Tumor confined to the bile duct histologically. T2: Tumor invades beyond the wall of the bile duct. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage II includes: IIA: (T3, N0, M0); IIB: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor invades the liver, gallbladder, pancreas, and/or unilateral branches or the portal vein (right or left) or hepatic artery (right or left). N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage III includes: T4, Any N, M0. T4: Tumor invades any of the following main portal vein or its branches bilaterally, common hepatic artery, or other adjacent structures, such as the colon, stomach, duodenum, or abdominal wall. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: Distant metastasis. (AJCC 6th ed.) - 2003
Inflammation of the anatomical structures of the inner ear secondary to an infectious process. Symptoms include severe vertigo, nausea, vomiting, anxiety, and pain. Viral etiology is most common, and recent history of an upper respiratory infection is common. In rare cases an infection of the middle ear can spread to the inner ear, resulting in a bacterial or fungal etiology.
An asymmetriy, i.e., difference in size, shape or position between the left and right ear.
A reduction in the strength of the eye muscles.
Back flow of gastric contents to the LARYNGOPHARYNX where it comes in contact with tissues of the upper aerodigestive tract. Laryngopharyngeal reflux is an extraesophageal manifestation of GASTROESOPHAGEAL REFLUX.
An electrocardiographic finding in which the ventricular rhythm is controlled by an electrical impulse from an artificial cardiac pacemaker. (CDISC)
Prostatic intraepithelial neoplasia characterized by the presence of morphologically malignant cells lining the acini and ducts. The malignant cells are enlarged, contain prominent nucleoli, and have increased nuclear/cytoloplasmic ratio. The malignant cells may grow within the ducts and acini in four architectural patterns: flat, tufting, micropapillary, and cribriform. The presence of high grade prostatic intraepithelial neoplasia in needle biopsy is a risk factor for the subsequent detection of carcinoma on repeat biopsy.
Prostatic intraepithelial neoplasia characterized by the proliferation of secretory cells with irregular spacing in the ducts and acini. Although some proliferating epithelial cells may contain prominent nucleoli, the cytologic atypia and architectural growth patterns that are seen in the high grade prostatic intraepithelial neoplasia are absent. The presence of low grade prostatic intraepithelial neoplasia in needle biopsy is not a risk factor for the subsequent detection of carcinoma on repeat biopsy.
Squamous cell carcinoma is a cancer that arises from particular cells called squamous cells. Squamous cells are found in the outer layer of skin and in the mucous membranes, which are the moist tissues that line body cavities such as the airways and intestines. Head and neck squamous cell carcinoma (HNSCC) develops in the mucous membranes of the mouth, nose, and throat.HNSCC is classified by its location: it can occur in the mouth (oral cavity), the middle part of the throat near the mouth (oropharynx), the space behind the nose (nasal cavity and paranasal sinuses), the upper part of the throat near the nasal cavity (nasopharynx), the voicebox (larynx), or the lower part of the throat near the larynx (hypopharynx). Depending on the location, the cancer can cause abnormal patches or open sores (ulcers) in the mouth and throat, unusual bleeding or pain in the mouth, sinus congestion that does not clear, sore throat, earache, pain when swallowing or difficulty swallowing, a hoarse voice, difficulty breathing, or enlarged lymph nodes.HNSCC can spread (metastasize) to other parts of the body, such as the lymph nodes or lungs. If it spreads, the cancer has a worse prognosis and can be fatal. About half of affected individuals survive more than five years after diagnosis.
A pharmaceutical preparation that combines buprenorphine, an OPIOID ANALGESIC with naloxone, a NARCOTIC ANTAGONIST to reduce the potential for NARCOTIC DEPENDENCE in the treatment of pain. It may also be used for OPIATE SUBSTITUTION THERAPY.
The d-threo-enantiomer of methylphenidate, a central nervous system stimulant, appearing to block the reuptake of norepinephrine and dopamine into the presynaptic neuron, increasing their availability in the extracellular space. The mechanism of action in Attention Deficit Hyperactivity Disorder is unknown. (NCI)
A recombinant form of human protein C with anti-thrombotic, anti-inflammatory, and profibrinolytic properties.
Trade name of escitalopram, the active S-enantiomer of the racemic citalopram.
Any commercial combination preparation, by Novartis, containing the decongestant pseudoephedrine hydrochloride used to relieve symptoms of cold and flu. Pseudoephedrine hydrochloride, a sympathomimetic agent, stimulates alpha-adrenergic receptors and causes vasoconstriction. This reduces blood flow, decreases swelling and prevents nasal and sinus congestion.
A propylamine derivative and selective ADRENERGIC UPTAKE INHIBITOR that is used in the treatment of ATTENTION DEFICIT HYPERACTIVITY DISORDER.
A methylphenidate derivative, DOPAMINE UPTAKE INHIBITOR and CENTRAL NERVOUS SYSTEM STIMULANT that is used in the treatment of ATTENTION DEFICIT HYPERACTIVITY DISORDER.
The sodium salt of ertapenem, a 1-beta-methyl carbapenem and a broad-spectrum beta-lactam antibiotic with bactericidal activity. Ertapenem binds to penicillin binding proteins (PBPs) located on the bacterial cell wall, in particular PBPs 2 and 3, thereby inhibiting the final transpeptidation step in the synthesis of peptidoglycan, an essential component of the bacterial cell wall. Inhibition of peptidoglycan synthesis results in weakening and lysis of the cell wall and cell death. In vitro, this agent has shown activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. Erapenem is resistant to hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases and extended-spectrum beta-lactamases.
The oxalate salt of escitalopram, a pure S-enantiomer of the racemic bicyclic phthalane derivative citalopram, with antidepressant activity. As a selective serotonin reuptake inhibitor (SSRI), escitalopram blocks the reuptake of serotonin by neurons in the central nervous system (CNS), thereby potentiating CNS serotonergic activity.
The mesylate salt form of ziprasidone, a benzothiazolylpiperazine derivative and an atypical antipsychotic agent with an antischizophrenic property. Ziprasidone mesylate functions as an antagonist at the dopamine D2 and serotonin 5-HT2A and 5-HT1D receptors, and as an agonist at the 5-HT1A receptor. Ziprasidone mesylate also inhibits the synaptic reuptake of serotonin and norepinephrine. The mechanism of action by which ziprasidone mesylate exerts its antischizophrenic effect is unknown but is potentially mediated through a combination of dopamine D2 and serotonin 5-HT2 antagonism. This agent also has antagonistic activity against histamine H1 and alpha-1-adrenergic receptors.
Increased chance of harm by preventing the conception of an offspring/child
Increased chance of harm during the period supporting the expulsion of an offspring / child at birth
Increased chance of conception to develop an offspring/child
Decreased chance of conception to develop an offspring/child
Increased chance of harm during the period supporting the bringing forth of an offspring / child
Increased chance of harm before, during, and immediately after the creation of an offspring / child
Increased chance of injury during the operative processes
Increased chance of harm during the time period immediately following the delivery of an offspring / child
Increased chance of harm in the process of replicating or giving rise to an offspring/child
The S-isomer of betaxolol, a selective beta-1 adrenergic receptor antagonist with anti-glaucoma activity and devoid of intrinsic sympathomimetic activity. When applied topically in the eye, levobetaxolol reduces aqueous humor secretion and lowers the intraocular pressure (IOP).
An agent composed of substance P (SP) conjugated to the ribosome-inactivating protein and neurotoxin saporin (SAP), isolated from the seeds of the plant Saponaria officinalis (SP-SAP), with potential analgesic activity. Upon administration, SP-SAP targets the SP receptor, neurokinin-1 receptor (NK-1R), located on neurons. When SP-SAP binds NK-1R and the receptor/conjugate complex internalizes, the saporin moiety inactivates ribosomes and prevents protein synthesis, which causes cell death, destroys NK-1R-expressing nerves and decreases pain perception.
A second-generation, semi-synthetic lipoglycopeptide antibiotic, with bactericidal activity against a variety of gram-positive bacteria. Upon administration, dalbavancin binds, at a site different from that of penicillins and cephalosporins, tightly to the D-alanyl-D-alanine portion of peptidoglycan chains, thereby preventing peptidoglycan elongation and interfering with bacterial cell wall synthesis. This leads to activation of bacterial autolysins and induces cell wall lysis.
A humanized monoclonal immunoglobulin G4 antibody to human INTEGRIN ALPHA4 that binds to the alpha4 subunit of INTEGRIN ALPHA4BETA1 and integrin alpha4beta7. It is used as an IMMUNOLOGIC FACTOR in the treatment of RELAPSING-REMITTING MULTIPLE SCLEROSIS and CROHN'S DISEASE.
A broad-spectrum peptide nucleic acid formulation comprised of breakdown products of casein, peptone, RNA and serum albumin, with potential anti-inflammatory, immunomodulatory, anti-anorectic and anti-cachexia activities. AVR118 mainly contains two peptides, peptide A and peptide B, in approximately a 1:1 ratio: peptide A (31 a. a.) is derived from bovine casein; peptide B (21 a. a.) is covalently linked via phosphodiester bond to a diadenosine unit. In addition, AVR118 contains nucleosides, nucleoside diphosphates and nucleoside monophosphates. Upon subcutaneous injection of AVR118, this agent affects the synthesis of many pro-inflammatory chemokines and cytokines, especially monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-8, IL-1 beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha). In particular, AVR118 stimulates macrophages to produce these mediators while in highly activated macrophages this agent inhibits their synthesis. This way, AVR118 may prevent the excessive release of cytokines seen during chemotherapy. Controlling the release of pro-inflammatory mediators may ultimately improve appetite and mood, increase strength and weight gain, and decrease fatigue.
An orally bioavailable synthetic peptide containing the amino acids D-glutamine and L-tryptophan connected by a gamma-glutamyl linkage with potential immunostimulating, antimicrobial and antineoplastic activities. Although the exact mechanism of action is unknown, golotimod appears to inhibit the expression of STAT-3, reversing immunosuppression and stimulating an anti-tumor immune response. This agent may stimulate the production of T-lymphocytes, in particular the helper T (Th1) cells, activate macrophages, and increase levels of interleukin 2 and interferon gamma. STAT-3, a transcription factor upregulated in many cancer cell types, is involved in tumor cell growth and survival and immunosuppression.
A thiocarbamate and squalene epoxidase inhibitor with antifungal activity. Liranaftate inhibits fungal squalene epoxidase, an enzyme that plays a key role in the synthesis of sterol which is essential for cell membrane integrity. By preventing ergosterol synthesis and causing accumulation of squalene, this agent increases cell membrane permeability, cell leakage and eventually cell lysis.
The acetate salt form of pramlintide, a peptide analogue of human amylin with 3 proline substitutions at position 25, 28 and 29, with antihyperglycemic activity. By mimicking amylin, pramlintide slows gastric emptying, inhibits digestive secretions (gastric acid, pancreatic enzymes, and bile), reduces glucagon secretion, and increases satiety; all of these actions are mediated mostly by glucose-sensitive areas in the brain stem. The overall result is a decrease in blood glucose levels. The use of pramlintide may cause an increased risk of insulin-induced hypoglycemia.
A third generation, non-sedating, selective histamine H1 receptor antagonist, with antihistamine, anti-inflammatory and potential anti-angiogenic activities. Levocetirizine competes with endogenous histamine for binding at peripheral H1-receptor sites on the effector cell surface. This prevents the negative symptoms associated with histamine release and an allergic reaction. In addition, as histamine plays an important role in angiogenesis during an allergic inflammatory reaction, blocking the action of histamine may modulate the expression of proangiogenic factors and thus may prevent angiogenesis. As a third-generation histamine H1 receptor antagonist, levocetirizine has fewer side effects than most second-generation antihistamines.
A humanized IgG1 monoclonal antibody directed against CD11a, the alpha subunit of human leukocyte-function-associated antigen type 1 (LFA-1), with immunosuppressant activity. Efalizumab binds to CD11a, which is expressed on all leukocytes, resulting in a reduction in the cell surface expression of CD11a. In addition, this agent inhibits the binding of LFA-1 to intercellular adhesion molecule-1 (ICAM-1), resulting in the inhibition of leukocyte adherence and the suppression of cell-mediated immunity. LFA-1 binding to ICAM-1 is involved in the activation of T lymphocytes, adhesion of T lymphocytes to endothelial cells, and migration of T lymphocytes to sites of inflammation.
A dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist with hypoglycemic activity. Ragaglitazar reduces blood pressure (BP) and improves endothelial function in antihypertensive studies.
A viral disorder characterized by high FEVER, dry COUGH, shortness of breath (DYSPNEA) or breathing difficulties, and atypical PNEUMONIA. A virus in the genus CORONAVIRUS is the suspected agent.
A polyhydroxylated stilbene extract from the seeds of Euphorbia lagascae, which inhibits protein tyrosine kinase Syk and induces apoptosis. (NCI)
An indole and pyrrole derivative that inhibits VEGF-R2 and PDGFR BETA RECEPTOR TYROSINE KINASES. It is used as an antineoplastic agent for the treatment of GASTROINTESTINAL STROMAL TUMORS, and for treatment of advanced or metastatic RENAL CELL CARCINOMA.
A nonpeptidomimetic quinolinone with potential antineoplastic activity. Tipifarnib binds to and inhibits the enzyme farnesyl protein transferase, an enzyme involved in protein processing (farnesylation) for signal transduction. By inhibiting the farnesylation of proteins, this agent prevents the activation of Ras oncogenes, inhibits cell growth, induces apoptosis, and inhibits angiogenesis. (NCI04)
A morpholine neurokinin-1 (NK1) receptor antagonist that is used in the management of nausea and vomiting caused by DRUG THERAPY, and for the prevention of POSTOPERATIVE NAUSEA AND VOMITING.
A benzazepine derivative and selective VASOPRESSIN V2 RECEPTOR antagonist that is used to treat euvolemic and hypervolemic HYPONATREMIA. It is also used in the treatment of rapidly progressing AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE to slow the rate of cyst development and renal insufficiency.
A dipeptide boronic acid analogue with antineoplastic activity. Bortezomib reversibly inhibits the 26S proteasome, a large protease complex that degrades ubiquinated proteins. By blocking the targeted proteolysis normally performed by the proteasome, bortezomib disrupts various cell signaling pathways, leading to cell cycle arrest, apoptosis, and inhibition of angiogenesis. Specifically, the agent inhibits nuclear factor (NF)-kappaB, a protein that is constitutively activated in some cancers, thereby interfering with NF-kappaB-mediated cell survival, tumor growth, and angiogenesis. In vivo, bortezomib delays tumor growth and enhances the cytotoxic effects of radiation and chemotherapy.
A prodrug form of amprenavir. In the body fosamprenavir is metabolized to amprenavir, a synthetic derivative of hydroxyethylamine sulfonamide that selectively binds to and inhibits human immunodeficiency virus (HIV) protease.
A carboline derivative and PHOSPHODIESTERASE 5 INHIBITOR that is used primarily to treat ERECTILE DYSFUNCTION; BENIGN PROSTATIC HYPERPLASIA and PRIMARY PULMONARY HYPERTENSION.
A sulfate salt form of atazanavir, an aza-dipeptide analogue with a bis-aryl substituent on the (hydroxethyl)hydrazine moiety with activity against both wild type and mutant forms of HIV protease. Atazanavir does not elevate serum lipids, a common problem with other protease inhibitors.
a drug used to treat attention deficit hyperactivity disorder (ADHD)
Malignant neoplasms involving the ductal systems of any of a number of organs, such as the MAMMARY GLANDS, the PANCREAS, the PROSTATE, or the LACRIMAL GLAND.
Copper ion requiring two electrons to return to its elemental state.
A triptan with specific affinity for the 5-hydroxytriptamine1B/1D receptor. Eletriptan hydrobromide binds to and acts at serotonin 5-HT1B receptors located on intracranial blood vessels which leads to vasoconstriction. This drug may also exerts its effects by binding to and activating 5-HT 1D receptors on sensory nerve endings in the trigeminal system, which results in the inhibition of pro-inflammatory neuropeptide release. Eletriptan hydrobromide is used to relieve pain or symptoms associated with migraine headaches.
Over curvature of the thoracic region, leading to a round back or if sever to a hump.
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Upward and/or sideward growth of anterior hair.
A highly diluted solution of sodium hypochlorite (0.5% w/v) with topical anti-infective activity. Dakin's solution is used as an antiseptic to clean infected topical wounds.
Abnormally increased amount of fluid in a joint cavity, usually as a result of joint inflammation.
Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.
A synthetic tricyclic derivative of carboxamide with antineoplastic properties. Lonarfanib binds to and inhibits farnesyl transferase, an enzyme involved in the post-translational modification and activation of Ras proteins. Ras proteins participate in numerous signalling pathways (proliferation, cytoskeletal organization), and play an important role in oncogenesis. Mutated ras proteins have been found in a wide range of human cancers. (NCI04)
Malnutrition, occurring in infants ages 1 month to 24 months, which is due to insufficient intake of food, dietary nutrients, or a pathophysiologic condition which prevents the absorption and utilization of food. Growth and development are markedly affected.
Malnutrition occurring in children ages 2 to 12 years, which is due to insufficient intake of food, dietary nutrients, or a pathophysiologic condition which prevents the absorption and utilization of food. Growth and development are markedly affected.
An imbalanced NUTRITIONAL STATUS resulting from excessive intake of nutrients. Generally, overnutrition generates an energy imbalance between food consumption and energy expenditure leading to disorders such as OBESITY.
An increase number of repeats of a genomic, tandemly repeated DNA sequence from one generation to the next.
Estrogenic STEROIDS with aliphatic hydrocarbon chain substitution on C17 or other position. 17-alpha-ALKYLATION renders the molecule more stable, resistant to metabolic degradation, and improves oral efficacy. Examples of synthetic alkyl estrogens include ETHINYL ESTRADIOL and MESTRANOL. Substitutions at other sites generates antiestrogenic and cytotoxic properties.
Characterized by the diverticulum arising from the extrahepatic biliary tree.
Characterized by the choledochocele dilatation of the distal portion of the COMMON BILE DUCT in the DUODENUM where the pancreatic duct (PANCREATIC DUCTS) enters.
Characterized by the presence of multiple extrahepatic and intrahepatic cysts.
Characterized by the presence of a singular or multiple intrahepatic cysts.
The instability of chromosomes is attributed to the continuous formation of novel chromosome mutations. These mutations form at an elevated rate in comparison to the normal cell population. The increased frequency of structural chromosome aberrations can be caused by an abnormally high incidence of DNA double-strand breaks and translocations. Screening for chromosomal breakage and rearrangement is used as a diagnostic tool in Fanconi anemia.
Errors in metabolic processing of STEROIDS resulting from inborn genetic mutations that are inherited or acquired in utero.
Agents that modulate the PHYSIOLOGIC ANGIOGENESIS process. This is accomplished by endogenous ANGIOGENIC PROTEINS and a variety of other chemicals and pharmaceutical agents.
Agents that induce or stimulate PHYSIOLOGIC ANGIOGENESIS or PATHOLOGIC ANGIOGENESIS.
Symptom characterized by the passage of stool once a week or less.
A benign or malignant sympathetic paraganglioma arising from paraganglia outside the adrenal gland. Clinical symptoms are related to secretion of catecholamines. Representative examples include the superior and inferior paraaortic and bladder paragangliomas.
Infections with bacteria of the family PISCIRICKETTSIACEAE, causing septicemic disease of salmonid fish (SALMONIDAE). Piscirickettsia-like bacteria are also associated with disease syndromes in non-salmonid fish.
A collective term for a group of around nine geometric and positional isomers of LINOLEIC ACID in which the trans/cis double bonds are conjugated, where double bonds alternate with single bonds.
Exposure to DNA-damaging agents and subsequent energy expenditures by a cell to repair DNA damage. Genotoxic stress elicits biochemical responses that either enhance cell survival or lead to cell death. These biochemical responses include DNA-damage-inducible repair and increasing expression of a variety of proteins by both transcriptional and post-transcriptional mechanisms. Genotoxic stresses frequently activate signal transduction pathways that originate in the cell membrane or cytoplasm, triggering similar phosphorylation cascades to those induced by the activation of cell-surface receptors.
The growth of INTESTINAL POLYPS. Growth processes include neoplastic (ADENOMA and CARCINOMA) and non-neoplastic (hyperplastic, mucosal, inflammatory, and other polyps).
Tumor or cancer of the human MAMMARY GLAND.
A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.
A metabolic disorder characterized by abnormal blood glucose levels.
A rare autosomal recessive lysosomal storage disease characterized by a deficient activity of the enzymes alpha-D-mannosidase or beta-mannosidase. Clinical signs and symptoms include hepatomegaly, splenomegaly, hearing loss, mental retardation, skeletal abnormalities, and recurrent respiratory infections.
A GLUCOSE-induced HYPERINSULINEMIA, a marker of insulin-resistant state. It is a mechanism to compensate for reduced sensitivity to insulin.
Heterodimers of FLAVONOIDS bound to LIGNANS.
A group of FLAVONOLS based on kaempferol. They are derived from naringenin and can be hydroxylated to QUERCETIN or reduced to leucopelargonidin.
A group of FLAVONOIDS characterized with a 4-ketone.
THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).
Aggregation of ERYTHROCYTES in vivo, caused by specific interactions such as those induced by antibodies.
Infections with viruses of the genus AVULAVIRUS, family PARAMYXOVIRIDAE. This includes NEWCASTLE DISEASE and other infections of domestic fowl.
Infections with viruses of the genus HENIPAVIRUS, family PARAMYXOVIRIDAE.
Pharmacological activities at the molecular level of DRUGS and other exogenous compounds that are used to treat DISEASES and affect normal BIOCHEMISTRY.
A chronic, clinically mild, infectious pneumonia of PIGS caused by MYCOPLASMA HYOPNEUMONIAE. Ninety percent of swine herds worldwide are infected with this economically costly disease that primarily affects animals aged two to six months old. The disease can be associated with porcine respiratory disease complex. PASTEURELLA MULTOCIDA is often found as a secondary infection.
A rapid onset form of SYSTEMIC SCLERODERMA with progressive widespread SKIN thickening over the arms, the legs and the trunk, resulting in stiffness and disability.
A modified glutathione analog. TLK286 is selectively activated by glutathione S-Transferase P1-1 into an alkylating metabolite which forms covalent linkages with nucleophillic centers in tumor cell DNA, thereby inducing a cellular stress response and cytotoxicity, and decreasing tumor proliferation. S-transferase P1-1 is an enzyme that is overexpressed in many human malignancies. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38367&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38367&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2641"" NCI Thesaurus)
A condition caused by the lack of intestinal PERISTALSIS or INTESTINAL MOTILITY without any mechanical obstruction. This interference of the flow of INTESTINAL CONTENTS often leads to INTESTINAL OBSTRUCTION. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced.
Infections with bacteria of the family Desulfovibrionaceae.
Infections with bacteria of the family Fusobacteriaceae, in the order Fusobacterales, phylum FUSOBACTERIA.
Infections with bacteria of the family FLAVOBACTERIACEAE.
Infections with bacteria of the family CYTOPHAGACEAE.
Infections with bacteria of the family MORAXELLACEAE.
The sodium salt of a phosphorothioate antisense oligonucleotide targeted to the initiation codon region of mRNA for the anti-apoptotic gene Bcl-2. Oblimersen inhibits Bcl-2 mRNA translation, which may result in decreased expression of the Bcl-2 protein and tumor cell apoptosis. This agent may enhance the efficacy of standard cytotoxic chemotherapy. The anti-apoptotic bcl-2 protein is an integral outer mitochondrial membrane protein (OMMP) that is overexpressed in some cancer cell types and is linked to tumor drug resistance.
Nodular tumor-like lesions or mucoid flesh, arising from tendon sheaths, LIGAMENTS, or JOINT CAPSULE, especially of the hands, wrists, or feet. They are not true cysts as they lack epithelial wall. They are distinguished from SYNOVIAL CYSTS by the lack of communication with a joint cavity or the SYNOVIAL MEMBRANE.
A recombinant immunotoxin consisting of the single chain anti-mesothelin monoclonal antibody SS1(dsFv) linked to Pseudomonas exotoxin PE-38. The monoclonal antibody moiety of the agent binds to cells that express mesothelin, a cell surface glycoprotein which may be overexpressed in ovarian cancer, mesotheliomas, and some squamous cell carcinomas; after internalization, the exotoxin moiety inactivates eukaryotic translation elongation factor 2, thereby disrupting tumor cell protein synthesis. (NCI04)
These compounds stimulate anabolism and inhibit catabolism. They stimulate the development of muscle mass, strength, and power.
A synthetic compound of the polyamine class of chemicals with potential antineoplastic activity. Natural endogenous polyamines bind to DNA and are involved in a number of cellular processes such as cell division, differentiation, and membrane function. SL11093 displaces these polyamines from their DNA binding sites, resulting in cessation of cell growth and cell death. (NCI04)
An anti-idiotype monoclonal antibody that mimics the disialoganglioside GD2, a cancer-associated antigen present on melanoma, small cell lung cancer, sarcoma, neuroblastoma and other malignancies. GD2 is a highly expressed glycosphingolipid by melanoma and other neuroectodermal tumors with only minimal expression on normal tissues. TriGem induces an immune response and can be the base for immunotherapy of melanoma and other cancers. (NCI04)
A naturally-occurring salinosporamide, isolated from the marine actinomycete Salinospora tropica, with potential antineoplastic activity. Marizomib irreversibly binds to and inhibits the 20S catalytic core subunit of the proteasome by covalently modifying its active site threonine residues; inhibition of ubiquitin-proteasome mediated proteolysis results in an accumulation of poly-ubiquitinated proteins, which may result in the disruption of cellular processes, cell cycle arrest, the induction of apoptosis, and the inhibition of tumor growth and angiogenesis. This agent more may more potent and selective than the proteasome inhibitor bortezomib.
An oral traditional Chinese herbal formulation in powder form containing a spray dried aqueous extract from the herbs Scutellaria baicalensis, Glycyrrhiza uralensis, Ziziphus jujuba and Paeonia lactiflora with potential immunomodulating and chemoprotective activities. Although the mechanism of actions remain to be fully elucidated, PHY906 possesses a wide range of pharmacological activities such as the enhancement of oral uptake of pharmacologically active agents, inhibition of CYP3A4, modulation of certain cytokines, macrophages and lymphocytes, and inhibition of expression of MMP, NF-kB, beta-glucuronidase, the NK-1 receptor, and the delta-opioid receptor.
A naphthalene derivative and CALCIMIMETIC AGENT that increases the sensitivity of PARATHYROID GLAND calcium-sensing receptors to serum calcium. This action reduces parathyroid hormone secretion and decreases serum calcium in the treatment of PARATHYROID DISEASES.
An oral contraceptive formulation containing the semisynthetic estrogen, ethinyl estradiol, combined with the synthetic progestin, norethindrone, with estrogenic and progestogenic activities, respectively. Ethinyl estradiol binds to and activates intracellular estrogen receptors found in the reproductive tract and other estrogen-responsive tissues. The activated complex enters the nucleus, binds to the estrogen response elements on DNA, activates the transcription of genes involved in the maintenance of the female reproductive system, inhibits the release of follicle stimulating hormone (FSH) from the anterior pituitary, and suppresses the development of the ovarian follicle. Norethindrone binds to intracellular progesterone receptors in progesterone-responsive tissues, such as the pituitary and those found in the reproductive system, and the activated ligand/receptor complex interacts with specific progesterone response elements on DNA, which results in the alteration in protein synthesis, the inhibition of ovulation, an increase in cervical mucus production, the induction of the secretory phase of the endometrial cycle, and the inhibition of luteinizing hormone (LH) release. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system and alters the structure of the endometrium to discourage implantation.
A neoplasm composed of spindle to ovoid cells which have morphologic and immunophenotypic characteristics of follicular dendritic cells. It affects lymph nodes and other sites including the tonsils, gastrointestinal tract, spleen, liver, soft tissues, skin, and oral cavity. It usually behaves as a low grade sarcoma. Treatment options include complete surgical removal of the tumor with or without adjuvant chemotherapy or radiotherapy. Recurrences have been reported in up to half of the cases.
A neoplastic proliferation of spindle to ovoid cells which show phenotypic features similar to those of interdigitating dendritic cells. The clinical course is generally aggressive. (WHO, 2008)
A neoplastic proliferation of Langerhans cells with overtly malignant cytologic features. It can be considered a higher grade variant of Langerhans cell histiocytosis (LCH) and it can present de novo or progress from antecedent LCH. (WHO, 2001)
Glucocorticoid-remediable aldosteronism is an autosomal dominant disorder characterized by hypertension, variable hyperaldosteronism, and abnormal adrenal steroid production, including 18-oxocortisol and 18-hydroxycortisol (Lifton et al., 1992). There is significant phenotypic heterogeneity, and some individuals never develop hypertension (Stowasser et al., 2000). Genetic Heterogeneity of Familial Hyperaldosteronism Familial hyperaldosteronism type II (HALD2; 605635) is caused by mutation in the CLCN2 gene (600570) on chromosome 3q27. Familial hyperaldosteronism type III (HALD3; 613677) is caused by mutation in the KCNJ5 gene (600734) on chromosome 11q24. Familial hyperaldosteronism type IV (HALD4; 617027) is caused by mutation in the CACNA1H gene (607904) on chromosome 16p13.
A heart disorder characterized by a defect in aortic valve structure or function.
Diamond-Blackfan anemia (DBA) in its classic form is characterized by a profound normochromic and usually macrocytic anemia with normal leukocytes and platelets, congenital malformations in up to 50% of affected individuals, and growth retardation in 30% of affected individuals. The hematologic complications occur in 90% of affected individuals during the first year of life. The phenotypic spectrum ranges from a mild form (e.g., mild anemia, no anemia with only subtle erythroid abnormalities, physical malformations without anemia) to a severe form of fetal anemia resulting in nonimmune hydrops fetalis. DBA is associated with an increased risk for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and solid tumors including osteogenic sarcoma.
A coagulation disorder caused by abnormalities in fibrin that result in defective clot formation. This disorder may be inherited or acquired.
Latent syphilis when infection was acquired more than twelve months previously.
In a position where one or both knees are on the ground.
When you're short of breath, it's hard or uncomfortable for you to take in the oxygen your body needs. You may feel as if you're not getting enough air. Sometimes you can have mild breathing problems because of a stuffy nose or intense exercise. But shortness of breath can also be a sign of a serious disease. Many conditions can make you feel short of breath:. -Lung conditions such as asthma, emphysema, or pneumonia. -Problems with your trachea or bronchi, which are part of your airway system. -Heart disease can make you feel breathless if your heart cannot pump enough blood to supply oxygen to your body. -Anxiety and panic attacks. -Allergies. If you often have trouble breathing, it is important to find out the cause.
An abnormality in the formation or distribution of pigment in the skin, hair or nails.
Drusen (singular, 'druse') are tiny yellow or white accumulations of extracellular material (lipofuscin) that build up in Bruch's membrane of the eye.
A lipoma usually occurring in the extremities of young children (usually boys). It is characterized by lobules of adipose tissue, separated by fibrous septa. The adipose tissue is composed of mature adipocytes and lipoblasts. The lipoblasts may be scarce, depending on the age of the patient.
A rare, benign, intraosseous neoplasm arising from tooth-forming tissues in the mandible and maxilla. It is characterized by the presence of odontogenic epithelium which is embedded in a fibrous stroma. Local enucleation of the tumor is curative.
Mulvihill-Smith syndrome is characterized by premature aging, multiple pigmented nevi, lack of facial subcutaneous fat, microcephaly, short stature, sensorineural hearing loss, and mental retardation. Immunodeficiency may also be a feature. Adult manifestations include the development of tumors, a sleep disorder with severe insomnia, and cognitive decline (summary by Yagihashi et al., 2009).
Pontocerebellar hypoplasia is a group of related conditions that affect the development of the brain. The term ""pontocerebellar"" refers to the pons and the cerebellum, which are the brain structures that are most severely affected in many forms of this disorder. The pons is located at the base of the brain in an area called the brainstem, where it transmits signals between the cerebellum and the rest of the brain. The cerebellum, which is located at the back of the brain, normally coordinates movement. The term ""hypoplasia"" refers to the underdevelopment of these brain regions.Pontocerebellar hypoplasia also causes impaired growth of other parts of the brain, leading to an unusually small head size (microcephaly). This microcephaly is usually not apparent at birth but becomes noticeable as brain growth continues to be slow in infancy and early childhood.Researchers have described at least ten types of pontocerebellar hypoplasia. All forms of this condition are characterized by impaired brain development, delayed development overall, problems with movement, and intellectual disability. The brain abnormalities are usually present at birth, and in some cases they can be detected before birth. Many children with pontocerebellar hypoplasia live only into infancy or childhood, although some affected individuals have lived into adulthood.The two major forms of pontocerebellar hypoplasia are designated as type 1 (PCH1) and type 2 (PCH2). In addition to the brain abnormalities described above, PCH1 causes problems with muscle movement resulting from a loss of specialized nerve cells called motor neurons in the spinal cord, similar to another genetic disorder known as spinal muscular atrophy. Individuals with PCH1 also have very weak muscle tone (hypotonia), joint deformities called contractures, vision impairment, and breathing and feeding problems that are evident from early infancy.Common features of PCH2 include a lack of voluntary motor skills (such as grasping objects, sitting, or walking), problems with swallowing (dysphagia), and an absence of communication, including speech. Affected children typically develop temporary jitteriness (generalized clonus) in early infancy, abnormal patterns of movement described as chorea or dystonia, and stiffness (spasticity). Many also have impaired vision and seizures.The other forms of pontocerebellar hypoplasia, designated as type 3 (PCH3) through type 10 (PCH10), appear to be rare and have each been reported in only a small number of individuals. Because the different types have overlapping features, and some are caused by mutations in the same genes, researchers have proposed that the types be considered as a spectrum instead of distinct conditions.
Inflammation of the trigone of the urinary bladder.
A disease or disorder that is associated with a transplanted kidney.
A disease or disorder that is associated with a transplanted liver.
A chronic granulomatous inflammation involving the deep dermis and the subcutaneous tissues. It is caused by Actinomycetes bacteria.
Narrowing or stricture of a vessel, duct or canal.
A sarcoma characterized by the presence of large, anaplastic malignant cells.
A congenital abnormality in which the meninges protrude through a defect in the spinal column or the cranium.
A connective tissue neoplasm formed by proliferation of mesodermal cells. Bone and soft tissue sarcomas are the main types of sarcoma. Sarcoma is usually highly malignant.
MCH is the HEMOGLOBIN divided by the ERYTHROCYTE COUNT.
An abnormality of XY sexual development characterized by the absence of both testes at birth.
A congenital deformity in which there is no laryngeal structure.
A primary headache disorder with characteristics of unilateral trigeminal pain that occurs in association with ipsilateral cranial autonomic symptoms (conjunctival injection and tearing). The disease manifests with strictly unilateral pain attacks of moderate-to-severe intensity. The typical patient may have 50 to 100 short attacks a day, lasting for 1 to 5 minutes. The attacks predominate during the daytime. Prominent, ipsilateral conjunctival injection and lacrimation regularly accompany the attacks. Trauma, arteriovenous malformations and pituitary adenoma may have a causative role.
Hyperthyroidism, the cause of which is present at birth.
Hypertrophy of the subcutaneous adipose tissue at the site of multiple subcutaneous injections of insulin.
The onset of acute renal failure, normally coupled with marked hypertension in a patient with scleroderma.
An overuse injury causing lateral knee pain that results from repetitive friction of the iliotibial band over the lateral femoral epicondyle.
Tubulointerstitial hemorrhage resulting from hantavirus infection.
Mycoses which manifest as infections of deep tissue or blood.
Gastroenteritis that is characterized by eosinophilic infiltration.
The position or physical attitude of the body.
The presence of abnormally large testes.
An inherited disorder that affects the metabolism of any acidic compound containing carbon in a covalent linkage.
A term that refers to glomerular damage resulting in hematuria, proteinuria, and azotemia. The histopathologic changes include rapidly progressive glomerulonephritis and membranoproliferative glomerulonephritis.
A benign or malignant neoplasm that affects the uterine corpus. Representative examples of benign neoplasms include leiomyoma, adenomyoma, endometrial stromal nodule, and endometrial polyp. Representative examples of malignant neoplasms include endometrial carcinoma, adenosarcoma, carcinosarcoma, and leiomyosarcoma.
An infectious disorder that occurs during the neonatal period. Representative examples include streptococcal infection, E.coli infection, and bacterial meningitis.
A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-V)
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Merosin-deficient congenital muscular dystrophy is an autosomal recessive form of muscular dystrophy characterized by muscle weakness apparent at birth or in the first 6 months of life. Patients show hypotonia, poor suck and cry, and delayed motor development; most never achieve independent ambulation. Most patients also have periventricular white matter abnormalities on brain imaging, but mental retardation and/or seizures occur only rarely (summary by Xiong et al., 2015).
A meningioma that affects the cerebellopontine angle.
Benign and malignant neoplasms which arise from or metastasize to the trigeminal or fifth cranial nerve which provides sensory innervation to the face, oral cavity and sinuses and the muscles of mastication. Clinical features may include facial pain or sensory loss or weakness of jaw closure.
A state of unconsciousness as a complication of diabetes mellitus. It occurs in cases of extreme HYPERGLYCEMIA or extreme HYPOGLYCEMIA as a complication of INSULIN therapy.
Blue skin coloration due to elevated blood levels of methemoglobin. The degree of cyanosis is directly correlated to the concentration of methemoglobin in the blood. As methemoglobin is not suitable for carrying oxygen, hypoxemia becomes a serious sequela.
A subtype of von Willebrand disease that results from a total or near total deficiency of VON WILLEBRAND FACTOR.
A myelodysplastic syndrome characterized by an anemia in which 15% or more of the erythroid precursors are ring sideroblasts. The ring sideroblast is an erythroid precursor in which one third or more of the nucleus is encircled by granules which are positive for iron stain. (WHO, 2001)
A disorder that follows infection but is distinct from the infection itself and its usual manifestations
Telangiectases (small dilated blood vessels) with a diffuse localization.
An inflammatory process characterized by the localized collection of polymorphonuclear neutrophils.
Deposition of mineral in normally non mineralized tissue
Hyperplasia characterized by the presence of a diffuse cellular infiltrate.
A morphologic finding indicating increased keratin formation, preservation of the nuclei in the superficial cells, and absence of the stratum granulosum in a skin or squamous mucosa sample.
A purely morphologic term that describes a neoplasm in which all or the majority of the neoplastic cells have a clear cytoplasm, when examined under light microscopy, using the conventional staining method (H-E). This term does not provide any information about the nature of the neoplasm (benign or malignant), cell of origin (e.g. epithelial versus mesenchymal versus hematopoietic), or prognosis. Further examination using special stains and/or immunohistochemistry is required to appropriately classify this tumor.
A usually aggressive carcinoma composed of large malignant cells which display neuroendocrine characteristics. It is characterized by the presence of high mitotic activity and necrotic changes. The vast majority of cases are positive for neuron-specific enolase. Representative examples include lung, breast, cervical, and thymic neuroendocrine carcinomas.
A large cell lung carcinoma characterized by the presence of rhabdoid cells.
A malignant epithelial neoplasm composed of atypical cells with glassy cytoplasm.
A malignant epithelial neoplasm characterized by the absence of neoplastic small epithelial cells. A representative example is the lung non-small cell carcinoma.
A well differentiated squamous cell carcinoma characterized by a papillary, exophytic growth pattern, hyperkeratosis, and absence of invasion of adjacent tissues.
A keratinizing squamous cell carcinoma characterized by the presence of horn pearls. Representative examples include squamous cell carcinomas of the face presenting as a cutaneous horn.
A squamous cell carcinoma characterized by the presence of cells with hyperchromatic nuclei, scant amount of cytoplasm, and peripheral nuclear palisading.
A squamous cell carcinoma characterized by the presence of malignant cells with clear cytoplasm.
A rare malignant tumor arising from the outer hair sheath and infundibulum on the face. It is considered the malignant counterpart of tricholemmoma. Complete surgical excision is required.
A papillary neoplasm of the urinary bladder in which the transitional cells form papillae. The papillary structures exhibit minimal architectural distortion and minimal atypia. Mitoses are infrequent. Patients are at an increased risk of developing new papillary lesions. Occasionally, the new lesions are urothelial carcinomas.
A transitional cell carcinoma characterized by a papillary growth pattern and lack of stromal invasion.
A transitional cell carcinoma characterized by a micropapillary growth pattern. Typical example is the micropapillary variant of infiltrating bladder urothelial carcinoma.
A high grade intraepithelial neoplasia in which there is marked architectural distortion and crowding of the glands, associated with severe cellular atypia. The neoplastic cells display pleomorphic and hyperchromatic nuclei.
A malignant neuroendocrine tumor arising from delta cells which produce somatostatin. It displays vascular invasion and metastasizes to other anatomic sites.
An endocrine neoplasm producing glucagon.
A glucagon-producing malignant endocrine neoplasm. It displays vascular invasion and metastasizes to other anatomic sites.
An uncommon type of hepatocelluar carcinoma, morphologically characterized by significant fibrosis around the sinusoid-like spaces and atrophy of the tumor trabeculae.
A tubular type adenoma of the breast in which, during pregnancy and lactation, the epithelial cells show extensive secretory changes.
An adenoma of the gastrointestinal tract mucosa which grossly and morphologically does not appear as an elevated or polypoid lesion.
An adenoma that arises from the large intestine and the appendix. It is characterized by prominent serration of the glands and the presence of generalized low-grade dysplasia.
An adenocarcinoma of the stomach arising from the parietal cells. It is characterized by the presence of malignant cells with eosinophilic, finely granular cytoplasm.
An anal adenocarcinoma arising from the epithelium of the anal glands. The overlying anal mucosa does not show evidence of neoplastic changes.
A carcinoid tumor characterized by a high mitotic rate, often associated with the presence of necrosis and nuclear pleomorphism.
A morphologic variant of minimally invasive lung adenocarcinoma characterized by the presence of Clara cells and/or type II cells.
A morphologic variant of minimally invasive lung adenocarcinoma characterized by tall columnar cells and mucin production.
A rare morphologic variant of bronchiolo-alveolar lung carcinoma characterized by the presence of both mucin and non-mucin producing cells.
Multifocal neoplastic proliferations of the glandular epithelium displaying a papillary pattern.
A type of carcinoma that comprises a minority of renal cell carcinomas. It is characterized by loss of chromosomes 1 and Y. Based on the cytoplasmic characteristics of the neoplastic cells, this type of carcinoma is classified as classic (typical) or eosinophilic. It has a much better prognosis than other renal cell carcinomas.
A high grade carcinoma of the kidney. It is not a distinct clinicopathological entity and includes a diverse group of renal cell carcinomas which have been transformed from a lower to a higher grade.
Also known as collecting duct carcinoma, this is a rare type of renal carcinoma. It arises from the collecting ducts of the renal medulla, and most authors suggest that this is an aggressive tumor.
A benign, well-circumscribed renal cortical neoplasm affecting females more often than males. Polycythemia has been reported in twelve-percent of patients.
A thyroid gland adenoma with increased cellularity and nuclear atypia. There is no capsular or vascular invasion. The clinical course is benign.
An adenocarcinoma arising from the thyroid gland showing only limited evidence of follicular cell differentiation. Microscopically, the adenocarcinoma cells are arranged in insular, solid, and trabecular patterns. There is associated necrosis, and vascular invasion. The prognosis depends on the tumor stage, complete or partial surgical removal of the tumor, and the degree of response to radioactive iodine therapy (adapted from WHO Tumors of Endocrine Organs, IARC Press, Lyon 2004)
An adenocarcinoma characterized by the presence of malignant glandular epithelium resembling the endocervical epithelium.
A rare, benign eccrine neoplasm usually arising on acral areas as a solitary papular or nodular lesion. Multiple lesions are referred as syringofibroadenomatosis. It is characterized by the presence of epithelial cuboidal cells forming anastomosing cords in a fibrovascular stroma.
A very rare, aggressive carcinoma of the sweat glands arising from malignant transformation of a long standing spiradenoma. It usually grows in the upper extremities, lower extremities, trunk, and head and neck. It has the tendency to recur and metastasize most often to the lymph nodes, bones, and lungs.
A carcinoma with eccrine differentiation arising from the sweat glands. It may arise de novo or as a malignant transformation of a pre-existing poroma. It usually grows in the legs, buttocks, feet, and trunk and usually presents as an ulcerative plaque. It is characterized by the presence of intraepidermal and dermal nests of malignant epithelial cells. It may recur after excision and metastasize to the lymph nodes and less frequently to distal anatomic sites.
A multicystic tumor arising in the inferior interatrial septum in the region of the atrioventricular node. The vast majority of patients present with complete heart block and a minority with partial heart block. Sudden death is reported in approximately 10% of the cases. It is a morphologically benign tumor composed of cuboidal, transitional, or squamoid cells. The cells may also show sebaceous differentiation and originate from the endoderm.
A mucinous adenocarcinoma characterized by the presence of malignant glandular cells which resemble the endocervical epithelium.
A cystic adenocarcinoma characterized by the presence of relatively uniform neoplastic cells which produce pancreatic enzymes and are arranged in acinar patterns. Signs and symptoms include abdominal pain, weight loss, nausea, and diarrhea. It usually has an aggressive clinical course.
An invasive adenocarcinoma characterized by the presence of focal or extensive neurosecretory cell differentiation with the formation of organoid patterns.
A general term used to describe carcinomas arising from epithelial cells that have been transformed into another cells type (metaplastic epithelial cells). A representative example is the adenocarcinoma arising in Barrett esophagus. This term is also used to describe carcinomas in which the malignant epithelial cells show differentiation towards another cell type. A representative example of the latter is the metaplastic breast carcinoma in which the malignant glandular cells show squamous, spindle cell, or chondroid/osseous differentiation.
An adenocarcinoma with morphologic characteristics similar to hepatocellular carcinoma, arising from an anatomic site other than the liver.
A thymic epithelial neoplasm characterized by the presence of spindle and/or oval neoplastic epithelial cells. Lymphocytic infiltration is minimal or absent. It may be associated with myasthenia gravis or pure red cell aplasia. The majority of cases occur in the anterior mediastinum as Masaoka stage I tumors. Approximately 20% of the cases occur as stage II or stage III tumors. Type A thymoma generally behaves as a benign tumor and the overall survival is reported to be 100% at 5 and 10 years.
A thymic epithelial neoplasm characterized by the presence of a lymphocyte-poor component similar to that seen in type A thymoma and a lymphocyte-rich component which contains neoplastic small polygonal epithelial cells. It may be associated with myasthenia gravis and pure red cell aplasia. The majority of cases occur in the anterior mediastinum as Masaoka stage I tumors. A minority of the cases occur as stage II or stage III tumors. The overall survival is reported to be 80-100% at 5 and 10 years.
A type AB thymoma which is characterized by an aggressive clinical course (capsular invasion, infiltration of the surrounding tissues) and can metastasize.
A thymic epithelial neoplasm characterized by the presence of expanded areas which resemble the normal thymic cortex. The neoplastic epithelial cells are small and scant and there is a dense T-lymphocytic component present. Areas of medullary differentiation with or without Hassall's corpuscles are also present. It may be associated with myasthenia gravis, pure red cell aplasia, and hypogammaglobulinemia. It has a low grade malignant potential. The majority of cases occur in the anterior mediastinum as Masaoka stage I tumors. A minority of the cases occur as stage II tumors.
A thymic epithelial neoplasm characterized by the presence of neoplastic large, polygonal epithelial cells with large vesicular nuclei and prominent nucleoli. The neoplastic cells are arranged around perivascular spaces and along septa. Immature T-lymphocytes are also present. It may be associated with myasthenia gravis, pure red cell aplasia, and hypogammaglobulinemia. It is a tumor of moderate malignancy. The majority of cases occur in the anterior mediastinum as Masaoka stage I, stage II, or stage III tumors. Metastatic, stage IV tumors occur less frequently.
A type B2 thymoma which is characterized by an aggressive clinical course (capsular invasion, infiltration of the surrounding tissues) and can metastasize.
A benign, well-circumscribed tumor of the neck occurring in adults. It is characterized by the presence of spindle cells, epithelial islands, and adipose tissue. There is no evidence of thymic origin or differentiation, despite the use of the term thymoma in the literature.
A rare, slow growing, primary carcinoma of the thyroid gland characterized by a lobulated architectural pattern and the presence of a biphasic cellular population composed of spindle epithelial cells and glandular cells. A small number of cases are composed exclusively of spindle epithelial cells or glandular cells.
An epithelial neoplasm that affects the thymus gland. This category includes thymomas and carcinomas.
A sex cord-stromal tumor of the testis in which the neoplastic cells do not show specific differentiation.
A sex cord-stromal tumor of the testis which may contain any combination of cell types, for example Sertoli cells, Leydig cells, and granulosa cells. Symptoms include testicular swelling and gynecomastia.
A very rare morphologic variant of glomus tumor with a size greater than 2 cm. The tumor arises in subfascial or visceral tissues. It is characterized by the presence of atypical mitotic figures, or marked nuclear atypia, or the combination of both. It has an aggressive clinical course.
A diffuse or multifocal proliferation of uniform nevoid polygonal cells in the leptomeninges. Cells may spread into the Virchow-Robin spaces without frank invasion of the brain. Diffuse melanocytosis carries a poor prognosis even in the absence of histologic malignancy. (WHO)
A usually well differentiated melanocytic neoplasm arising from the meninges. It is characterized by the presence of epithelioid, fusiform, polyhedral, and spindle melanocytes without evidence of hemorrhage, necrosis, or high mitotic activity. Presenting symptoms include headache, vomiting, and neurological manifestations. Complete excision is usually curative.
A meningeal melanoma with secondary diffuse meningeal spread. (WHO)
An acral lentiginous melanoma affecting mucosal surfaces.
A benign proliferation of epithelioid or spindled melanocytes usually in the upper or mid dermis in a background of congenital melanocytic nevus. The congenital melanocytic nevus is usually of the deep type, involving the dermis and extending into the subcutaneous tissue. It presents as a dark plaque or nodule above a giant congenital melanocytic nevus.
A morphologic variant of fibroma characterized by increased cellularity.
A localized neoplasm of probable fibroblastic derivation. It is characterized by the presence of round to spindle-shaped cells, hylanized stroma formation, thin-walled branching blood vessels, and thin bands of collagen.
A malignant neoplasm of probable fibroblastic derivation. It is characterized by the presence of atypical round to spindle-shaped cells, increased cellularity, necrotic change and high mitotic activity.
A benign tumor that consists chiefly of fibrous CONNECTIVE TISSUE, with variable numbers of MUSCLE CELLS forming portions of the neoplasm (From Stedman's, 27th ed).
A benign myofibroblastic neoplasm, usually arising in the pelviperineal region. It is characterized by the presence of neoplastic spindle to round cells, dilated thin walled vessels, and stromal edema. Most patients present with painless circumscribed masses.
A rare lung neoplasm that occurs in the intrauterine and perinatal period. It is characterized by the proliferation of spindle cells in an interstitial, peribronchial pattern. Surgical resection of the involved lung parenchyma is the treatment of choice.
A rare, well-circumscribed, pseudo-encapsulated benign fibrous histiocytoma that arises entirely within the subcutaneous tissue or deep soft tissue. It usually affects the extremities or the head and neck region. It recurs locally in a minority of cases.
An intermediate cutaneous fibrohistiocytic neoplasm that usually affects children and young adults. It is a multinodular, poorly circumscribed tumor characterized by the presence of multinucleated giant cells, mononuclear histiocyte-like cells, and spindle fibroblast-like cells arranged in a plexiform pattern.
A low malignant potential soft tissue neoplasm of uncertain differentiation. It typically affects young patients, presenting as a slowly growing nodular or cystic tumor mass, most often in the subcutaneous tissues of the extremities. Occasionally, patients have systemic symptoms (anemia, fever, and weight loss). This tumor has a relatively good prognosis. A minority of patients develop local recurrences. Metastases are rare.
A rare soft tissue tumor of uncertain lineage characterized by the presence of neoplastic spindle to round cells forming cords in a fibromyxoid stroma. The lesions are associated with the formation of metaplastic bone. Most patients present with painless subcutaneous masses. Recurrences have been reported in a minority of patients.
An intermediate, locally aggressive lipomatous neoplasm. Microscopically, the adipose tissue contains large and pleomorphic lipoblasts, and is dissected by fibrous septa containing spindle cells. It requires a wide local excision, may recur locally, but never metastasizes.
A liposarcoma characterized by the presence of a fibroblastic component.
A rare benign adipose tissue neoplasm characterized by nests and cord of abundant univacuolated and multivacuolated lipoblasts and mature adipocytes in a prominent myxoid to hyalinized chondroid matrix admix. It predominantly affects females.
A rare benign skeletal muscle neoplasm arising from the female genital tract. It is characterized by the presence of small nucleated rhabdomyoblasts within a fibrous and myxoid stroma.
An uncommon variant of rhabdomyosarcoma characterized by the presence of whorls of spindle cells forming a storiform pattern. In children it usually arises in the paratesticular region. In adults it usually arises from the deep soft tissues in the head and neck.
A gastrointestinal stromal tumor that is characterized by a maximum diameter equal or less than 5 cm (gastric localization), or equal or less than 2 cm (intestinal localization) and no more than 5 mitotic figures per 50 high power fields.
A benign encapsulated neoplasm of the kidney, characterized by the presence of cysts separated by septa. There are no solid areas present. The septa are lined by one layer of epithelial cells that have eosinophilic or clear cytoplasm. The cystic spaces contain serous or hemorrhagic fluid.
A variant of Wilms tumor of the kidney characterized by the presence of cystic spaces separated by septa. The septa contain immature epithelial cells, immature stromal cells, and blastema cells. Surgical resection is usually curative.
A benign, solitary, and partially cystic neoplasm arising from the kidney. It occurs in children and adults. Presenting symptoms include hematuria and polycythemia. It is characterized by the presence of epithelial nodules embedded in a stroma containing spindle cells.
A benign neoplasm characterized by the proliferation of cells with myoepithelial differentiation around spaces which are lined by epithelial cells.
A term that refers to teratoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, or mixed forms of these tumors.
A gestational trophoblastic tumor characterized by the presence of a monomorphous cellular population of intermediate trophoblastic cells infiltrating in a nodular pattern.
A low grade osteosarcoma arising from the medullary portion of the bone. It affects the long bones and is characterized by the presence of fibroblastic stroma and osteoid production. Pain and swelling are the usual sign and symptom. The prognosis is more favorable than conventional osteosarcoma.
A usually aggressive high grade malignant bone-forming mesenchymal neoplasm arising from the surface of the bone.
A high grade malignant bone-forming mesenchymal neoplasm producing osteoid. The tumor arises from the medullary portion of the bone. It affects the long bones and most commonly, the distal femur, proximal tibia, and proximal humerus. Pain with or without a palpable mass is the most common clinical presentation. It usually has an aggressive growth and may metastasize through the hematogenous route. The lung is the most frequent site of metastasis.
A rare, usually low grade chondrosarcoma characterized by the presence of tumor cells with clear cytoplasm. It usually arises in the epiphyseal ends of long bones.
An uncommon malignant tumor arising from the tendon sheath. Morphologically, it is characterized by the presence of a cellular infiltrate reminiscent of a giant cell tumor with prominent malignant characteristics. Recurrent giant cell tumors with a sarcomatous dedifferentiation are included in this category as well.
A slow-growing malignant bone tumor arising from the remnants of the notochord and occurring in the base of the skull. The tumor is characterized by a lobulated growth pattern, myxoid stroma formation, and the presence of physaliphorous cells and cartilage.
A high-grade malignant bone tumor arising from the remnants of the notochord. It is characterized by a lobulated growth pattern, myxoid stroma formation, the presence of physaliphorous cells, and a sarcomatous component.
A rare, usually benign myoepithelial tumor characterized by the presence of epithelioid, often vacuolated neoplastic cells. Most patients present with painless swelling in the subcutaneous or subfascial soft tissues of the extremities.
A choroid plexus papilloma characterized by increased mitotic activity.
A benign glial-neuronal neoplasm. It is usually supratentorial, located, generally, in the cortex and occurs in children and young adults with a long-standing history of partial seizures. A histologic hallmark of this tumor is the 'specific glioneuronal element', characterized by columns, made up of bundles of axons, oriented perpendicularly to the cortical surface. (Adapted from WHO)
An astrocytic tumor affecting young people. Morphologically, it is characterized by the presence of collagenous tissue surrounding neoplastic astrocytes. In some cases the collagen is produced by the tumor cells (desmoplastic astrocytoma), whereas in others it is produced by mesenchymal cells (mixed glioma/fibroma).
A medulloblastoma composed of large cells with prominent nucleoli and a larger amount of cytoplasm in contrast with the cells of the classic medulloblastoma.
An aggressive malignant embryonal neoplasm arising from the central nervous system. It is composed of cells with a large eccentric nucleus, prominent nucleolus, and abundant cytoplasm. Mutations of the INI1 gene or very rarely SMARCA4 (BRG1) gene are present. The vast majority of cases occur in childhood. Symptoms include lethargy, vomiting, cranial nerve palsy, headache, and hemiplegia.
A retinoblastoma characterized by the absence of a distinct retinal mass and the presence of malignant cells diffusely infiltrating the retina. It is often confused with uveitis and endophthalmitis, resulting in delayed diagnosis of the malignancy.
This term applies to a retinoblastoma which has regressed spontaneously. Histologic examination of the tumor reveals benign-appearing tumor cells, with no evidence of nuclear atypia, pleomorphism, or rosettes formation. There is a well-vascularized stroma which contains calcifications.
A very rare malignant tumor with morphologic features similar to those of benign perineurioma of soft tissue along with hypercellularity, nuclear atypia, hyperchromasia, and a high mitotic rate.
A subtype of classical Hodgkin lymphoma with scattered Hodgkin and Reed-Sternberg cells and a nodular or less often diffuse cellular background consisting of small lymphocytes and with an absence of neutrophils and eosinophils. (WHO, 2008)
Cyclic hexapeptides of proline-ornithine-threonine-proline-threonine-serine. The cyclization with a single non-peptide bond can lead them to be incorrectly called DEPSIPEPTIDES, but the echinocandins lack ester links. Antifungal activity is via inhibition of 1,3-beta-glucan synthase production of BETA-GLUCANS.
Any substance that inhibits tyrosine kinase, an enzyme involved in the transduction and processing of many extracellular and intracellular signals including cell proliferation. Inhibition of tyrosine kinase may result in inhibition of cell growth and cell proliferation.
Susceptible to a decrease in normal frequency of defecation accompanied by difficult or incomplete passage of stool, which may compromise health.
Susceptible to involuntary passage of urine occurring soon after a strong sensation or urgency to void, which may compromise health.
Potential for an abnormal regulation of fluid volume balance resulting in more fluids than the body can get rid of or less fluids than the body can take in.
Susceptible to deterioration of body systems as the result of prescribed or unavoidable musculoskeletal inactivity, which may compromise health.
Potential for allergic reaction to products containing processed natural rubber latex.
Susceptible to experiencing discomfort associated with a desire or need for more contact with others, which may compromise health.
Susceptible to difficulty in fulfilling care responsibilities, expectations and/or behaviors for family or significant others, which may compromise health.
Susceptible to an impaired ability to experience and integrate meaning and purpose in life through connectedness within self, literature, nature, and/or a power greater than oneself, which may compromise health.
Susceptible to disruption in the circulation, sensation, and motion of an extremity, which may compromise health.
Potential for damage to skin, soft tissue, joints, ligaments, bones, eyes, nerves and blood and lymph vessels as a result of the mechanism of compression or stretching that occurs while positioning the patient to expose the surgical site especially in patients identified at risk for perioperative pressure injury.
Susceptible to delay of 25% or more in one or more of the areas of social or self-regulatory behavior, or in cognitive, language, gross, or fine motor skills, which may compromise health.
Susceptible to disintegration in the pattern of modulation of the physiological and neurobehavioral systems of functioning, which may compromise health.
Increased chance of destroying a limb or essential part of the body
Susceptible to behaviors in which an individual demonstrates that he or she can be physically, emotionally, and/or sexually harmful to self.
Susceptible to sustained maladaptive response to a traumatic, overwhelming event, which may compromise health.
Susceptible to physiological and/or psychosocial disturbance following transfer from one environment to another, which may compromise health.
Susceptible to the lived experience of lack of control over a situation, including apperception that one's actions do not significantly affect the outcome, which may compromise health.
Susceptible to developing a negative perception of self-worth in response to a current situation, which may compromise health.
Increased chance of conditions that results in falls
A pattern of management of adaptive tasks by primary person (family member, significant other, or close friend) involved with the client's health challenge, which can be strengthened.
A pattern of community activities for adaptation and problem-solving for meeting the demands or needs of the community, which can be strengthened.
A pattern of experiencing and integrating meaning and purpose in life through connectedness with self, others, art, music, literature, nature, and/or a power greater than oneself, which can be strengthened.
Change in or modification of the systolic or diastolic pressure
Disruption in tooth development/eruption pattern or structural integrity of individual teeth.
Any agent that binds to the gonadotropin releasing hormone receptors and causes both the inhibition of gonadotropin releasing hormone activities and a decrease in the pituitary output of follicle stimulating hormone and luteinizing hormone.
Agents administered before, with, or after cancer therapy to reduce or prevent damage or toxicity to the normal cells. (NCI)
The classic pentad of TTP includes hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and nonfocal neurologic findings, decreased renal function, and fever. Congenital TTP, also known as Schulman-Upshaw syndrome, is characterized by neonatal onset, response to fresh plasma infusion, and frequent relapses (Savasan et al., 2003; Kokame et al., 2002). Acquired TTP, which is usually sporadic, usually occurs in adults and is caused by an IgG inhibitor against the von Willebrand factor-cleaving protease.
Hemolytic uremic syndrome caused by gastrointestinal infection, usually with shiga toxin-producing enterobacteria.
A subtype of myelodysplastic syndrome which initially lacks findings appropriate for classification into any other myelodysplastic category. There are no specific morphologic findings. The diagnosis can be made in the following instances: 1. in cases of refractory cytopenia with unilineage dysplasia or refractory cytopenia with multilineage dysplasia but with 1% blasts in the peripheral blood; 2: in cases of myelodysplastic syndrome with unilineage dysplasia which are associated with pancytopenia; 3: in cases with persistent cytopenia (s) with 1% or fewer blasts in the blood and fewer than 5% in the bone marrow, unequivocal dysplasia in less than 10% of the cells in one or more myeloid lineages, and cytogenetic abnormalities considered as presumptive evidence of myelodysplastic syndrome. (WHO, 2008)
An abnormal enlargement of the renal calices, the system of ducts of the kidney that collect urine. [HPO:sdoelken]
The local spread of tumor cells of a malignant neoplasm through infiltration or destruction of adjacent tissue; for epithelial neoplasms, invasion signifies infiltration beneath the epithelial basement membrane.
A malignant neoplasm arising from mesothelial cells. It is characterized by the presence of a dense collagenous tissue and atypical neoplastic cells. Sarcomatoid features, collagenous necrosis, and infiltration of muscle and adipose tissue may be present. It occurs in the pleura and less commonly in the peritoneum.
Some forgetfulness can be a normal part of aging. However, some people have more memory problems than other people their age. This condition is called mild cognitive impairment, or MCI. People with MCI can take care of themselves and do their normal activities. MCI memory problems may include. -Losing things often. -Forgetting to go to events and appointments. -Having more trouble coming up with words than other people of the same age. Memory problems can also have other causes, including certain medicines and diseases that affect the blood vessels that supply the brain. Some of the problems brought on by these conditions can be managed or reversed. Your health care provider can do thinking, memory, and language tests to see if you have MCI. You may also need to see a specialist for more tests. Because MCI may be an early sign of Alzheimer's disease, it's really important to see your health care provider every 6 to 12 months. At this time, there is no proven drug treatment for MCI. Your health care provider can check to see if you have any changes in your memory or thinking skills over time. NIH: National Institute on Aging.
This is the original version, published in 1974. It has a maximum score of 14.
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis
Susceptible to unpredicted death of an infant.
A test result that reports the diastolic and systolic pressure of the blood.
A malposition of the pupil owing to a developmental defect of the iris.
Clinical triad of uveitis, glaucoma, and hyphema (UGH), especially associated with the early anterior chamber intraocular lens (IOL).Glaucoma is believed to be caused by movement of the IOL against the iris causing release of inflammatory and red blood cell debris, which obstruct the trabecular meshwork. The haptic also may cause direct damage to the trabecular meshwork contributing to the glaucoma. Incidence of UGH is dependent on both surgical methodology applied in the cataract population and type of IOL used. UGH is particularly common if metal clip lenses have been used. Components of the condition may be reversed if the offending IOL is removed before permanent damage has occurred.
The lactate form of amsacrine, an aminoacridine analog and topoisomerase II inhibitor, with antineoplastic activity. Although the exact relationship between DNA binding and its activity has yet to be fully elucidated, amsacrine intercalates DNA through its acridine moiety, and its nonintercalative headgroup impedes topoisomerase II activity, augmenting enzyme-mediated DNA cleavage and resulting in DNA double-strand breaks. This ultimately induces programmed cell death.
Death of a live newborn during the first 7 days of life.
Death of an infant after 28 days of age and before 1 year of age
Abnormally low concentration of vitamin D3 (cholecalciferol) in the blood.
A morphologic variant of glioblastoma characterized by the presence of a highly proliferative and monotonous population of malignant small glial cells.
Cutaneous lesion induced by minor, but constant mechanical trauma occurring typically on the lateral edges of the nasal root or on top of or behind the auricle.
The blood pressure in the ARTERIES. It is commonly measured with a SPHYGMOMANOMETER on the upper arm which represents the arterial pressure in the BRACHIAL ARTERY.
A rare, benign neoplasm that most often manifests as a multiloculated cystic renal mass. It is characterized by the presence of solid and cystic components. The solid components contain a mixture of epithelial and stromal elements.
An adamantinoma arising from the tibia. The tibia is the site which is more frequently involved by adamantinoma (80-90% of cases).
Abnormal function of the left ventricule during left ventricular relaxation and filling.
A pattern of exchanging information and ideas with others, which can be strengthened.
A pattern of family functioning to support the well-being of its members, which can be strengthened.
A pattern of natural, periodic suspension of relative consciousness to provide rest and sustain a desired lifestyle, which can be strengthened.
A pattern of perceptions or ideas about the self, which can be strengthened.
A person worthy of responsibility or trust or one held accountable.
An area of real estate divided into multiple lots.
The value of the sum of the primary and secondary Gleason scores (range 2-10). If three patterns are identified, it is the sum of the primary pattern score and the score of the least well-differentiated pattern.
A paraneoplastic disorder affecting the skeletal system. It associated with one of four tumor types: phosphaturic mesenchymal tumor, mixed connective tissue type; osteoblastoma-like tumor; ossifying fibroma-like tumor or non-ossifying fibroma-like tumor. These neoplasms secrete fibroblast growth factor 23, which in addition to causing decreased renal phosphate reabsorption also affects the expression of 25-hydroxy-1-alpha-hydroxylase resulting in poor bone mineralization. Clinical signs include fractures, bone pain and muscle weakness. Once lesions are detected, prognosis is extremely favorable as resection most often results in cure.
A broad classification of disorders that affect the cell-mediated aspect of the immune response. Circulating numbers of T lymphocytes are decreased or ineffective.
An uncommon benign lesion in the vulva. It manifests with multiple papular lesions which are purple in color. They are usually asymptomatic. Histologically, there is hyperkeratosis, papillomatosis, and dilated blood vessels in the papillary dermis.
A benign neoplasm arising from the lymphatic vessels.
A benign neoplasm affecting the skin. It is composed of fibrohistiocytic cells, spindle fibroblastic cells, and histiocytes arranged in a storiform pattern.
Central centrifugal cicatricial alopecia (CCCA) is the most common type of primary scarring alopecia affecting women of African ancestry, with an estimated prevalence of 2.7 to 5.6%. It may be triggered by hair-grooming habits; however, familial occurrence has been reported. Mean age at presentation is 36 years. The first sign is often unexplained hair breakage, followed by hair thinning, primarily involving the vertex scalp and progressing centrifugally. Histopathologic examination shows varying degrees of lymphocytic inflammation, follicular degeneration, and fibrosis (Malki et al., 2019).
Hyperhidrosis palmaris et plantaris (HYPRPP) is characterized by excessive perspiration of the eccrine sweat gland in the palm, sole, and axilla. Perspiration in those affected may be aggravated by emotional stimuli (summary by Higashimoto et al., 2006). Stolman (1998) noted that hyperhidrosis may be complicated by skin maceration as well as secondary microbial infections, and that treatment modalities are associated with complications.
Hereditary mucoepithelial dysplasia (HMD) is a rare autosomal dominant genodermatosis characterized by onset in infancy of a panepithelial defect involving the oral, nasal, conjunctival, vaginal, cervical, perineal, urethral, and bladder mucosa. Patients develop cataracts, blindness, nonscarring alopecia, perineal psoriasiform lesions, and follicular keratoses (Witkop et al., 1982). Although 1 family was reported to have progressive severe interstitial lung disease (Witkop et al., 1979), this feature has not been reported in other families and is not considered a criterion for diagnosis (review by Boralevi et al., 2005).
A chronic autoimmune phenomenon characterized by fibrosis (or hardening) and vascular alterations of the skin.
Carpenter syndrome is a condition characterized by the premature fusion of certain skull bones (craniosynostosis), abnormalities of the fingers and toes, and other developmental problems.Craniosynostosis prevents the skull from growing normally, frequently giving the head a pointed appearance (acrocephaly). In severely affected individuals, the abnormal fusion of the skull bones results in a deformity called a cloverleaf skull. Craniosynostosis can cause differences between the two sides of the head and face (craniofacial asymmetry). Early fusion of the skull bones can affect the development of the brain and lead to increased pressure within the skull (intracranial pressure). Premature fusion of the skull bones can cause several characteristic facial features in people with Carpenter syndrome. Distinctive facial features may include a flat nasal bridge, outside corners of the eyes that point downward (down-slanting palpebral fissures), low-set and abnormally shaped ears, underdeveloped upper and lower jaws, and abnormal eye shape. Some affected individuals also have dental abnormalities including small primary (baby) teeth. Vision problems also frequently occur.Abnormalities of the fingers and toes include fusion of the skin between two or more fingers or toes (cutaneous syndactyly), unusually short fingers or toes (brachydactyly), or extra fingers or toes (polydactyly). In Carpenter syndrome, cutaneous syndactyly is most common between the third (middle) and fourth (ring) fingers, and polydactyly frequently occurs next to the big or second toe or the fifth (pinky) finger.People with Carpenter syndrome often have intellectual disability, which can range from mild to profound. However, some individuals with this condition have normal intelligence. The cause of intellectual disability is unknown, as the severity of craniosynostosis does not appear to be related to the severity of intellectual disability.Other features of Carpenter syndrome include obesity that begins in childhood, a soft out-pouching around the belly-button (umbilical hernia), hearing loss, and heart defects. Additional skeletal abnormalities such as deformed hips, a rounded upper back that also curves to the side (kyphoscoliosis), and knees that are angled inward (genu valgum) frequently occur. Nearly all affected males have genital abnormalities, most frequently undescended testes (cryptorchidism).A few people with Carpenter syndrome have organs or tissues within their chest and abdomen that are in mirror-image reversed positions. This abnormal placement may affect several internal organs (situs inversus); just the heart (dextrocardia), placing the heart on the right side of the body instead of on the left; or only the major (great) arteries of the heart, altering blood flow.The signs and symptoms of this disorder vary considerably, even within the same family. The life expectancy for individuals with Carpenter syndrome is shortened but extremely variable.The signs and symptoms of Carpenter syndrome are similar to another genetic condition called Greig cephalopolysyndactyly syndrome. The overlapping features, which include craniosynostosis, polydactyly, and heart abnormalities, can cause these two conditions to be misdiagnosed; genetic testing is often required for an accurate diagnosis.
Cardiofaciocutaneous (CFC) syndrome is characterized by cardiac abnormalities (pulmonic stenosis and other valve dysplasias, septal defects, hypertrophic cardiomyopathy, rhythm disturbances), distinctive craniofacial appearance, and cutaneous abnormalities (including xerosis, hyperkeratosis, ichthyosis, keratosis pilaris, ulerythema ophryogenes, eczema, pigmented moles, hemangiomas, and palmoplantar hyperkeratosis). The hair is typically sparse, curly, fine or thick, woolly or brittle; eyelashes and eyebrows may be absent or sparse. Nails may be dystrophic or fast growing. Some form of neurologic and/or cognitive delay (ranging from mild to severe) is seen in all affected individuals. Neoplasia, mostly acute lymphoblastic leukemia (ALL), has been reported in some individuals.
Keratitis-ichthyosis-deafness (KID) syndrome is characterized by eye problems, skin abnormalities, and hearing loss.People with KID syndrome usually have keratitis, which is inflammation of the front surface of the eye (the cornea). The keratitis may cause pain, increased sensitivity to light (photophobia), abnormal blood vessel growth over the cornea (neovascularization), and scarring. Over time, affected individuals experience a loss of sharp vision (reduced visual acuity); in severe cases the keratitis can lead to blindness.Most people with KID syndrome have thick, hard skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Affected individuals also have thick, reddened patches of skin (erythrokeratoderma) that are dry and scaly (ichthyosis). These dry patches can occur anywhere on the body, although they most commonly affect the neck, groin, and armpits. Breaks in the skin often occur and may lead to infections. In severe cases these infections can be life-threatening, especially in infancy. Approximately 12 percent of people with KID syndrome develop a type of skin cancer called squamous cell carcinoma, which may also affect mucous membranes such as the lining of the mouth.Partial hair loss is a common feature of KID syndrome, and often affects the eyebrows and eyelashes. Affected individuals may also have small, abnormally formed nails.Hearing loss in this condition is usually profound, but occasionally is less severe.
Multiple familial trichoepithelioma, also called epithelioma adenoides cysticum (EAC), is an autosomal dominant dermatosis characterized by the presence of many skin tumors predominantly on the face. Since histologic examination shows dermal aggregates of basaloid cells with connection to or differentiation toward hair follicles, this disorder has been thought to represent a benign hamartoma of the pilosebaceous apparatus. Trichoepitheliomas can degenerate into basal cell carcinoma (Johnson and Bennett, 1993). Because BRSS, familial cylindromatosis, and MFT1 are allelic, and because different manifestations of each have been described within a single family, many consider these disorders to represent a phenotypic spectrum of a single disease entity (Lee et al., 2005; Bowen et al., 2005; Young et al., 2006; Saggar et al., 2008). Blake and Toro (2009) provided a detailed review of the spectrum of disorders associated with CYLD mutations.
Tumor necrosis factor receptor-associated periodic syndrome (commonly known as TRAPS) is a condition characterized by recurrent episodes of fever. These fevers typically last about 3 weeks but can last from a few days to a few months. The frequency of the episodes varies greatly among affected individuals; fevers can occur anywhere between every 6 weeks to every few years. Some individuals can go many years without having a fever episode. Fever episodes usually occur spontaneously, but sometimes they can be brought on by a variety of triggers, such as minor injury, infection, stress, exercise, or hormonal changes.During episodes of fever, people with TRAPS can have additional signs and symptoms. These include abdominal and muscle pain and a spreading skin rash, typically found on the limbs. Affected individuals may also experience puffiness or swelling in the skin around the eyes (periorbital edema); joint pain; and inflammation in various areas of the body including the eyes, heart muscle, certain joints, throat, or mucous membranes such as the moist lining of the mouth and digestive tract. Occasionally, people with TRAPS develop amyloidosis, an abnormal buildup of a protein called amyloid in the kidneys that can lead to kidney failure. It is estimated that 15 to 20 percent of people with TRAPS develop amyloidosis, typically in mid-adulthood.The fever episodes characteristic of TRAPS can begin at any age, from infancy to late adulthood, but most people have their first episode in childhood.
An uncommon intraepithelial malignant neoplasm of eccrine or apocrine origin, arising from the vulva. It usually affects post-menopausal women. In approximately 10-20% of the cases there is an associated anorectal, or urothelial carcinoma or a skin appendage adenocarcinoma identified. It presents as a red, eczematous lesion. Microscopically, it is characterized by the presence of the typical Paget cells which are large, round cells with abundant cytoplasm and prominent nuclei.
A glomus tumor arising from the skin. It is characterized by the presence of dilated veins surrounded by glomus cells.
A small, slow growing, benign neoplasm arising from the tendon sheaths. The tumor is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation.
Small white or flesh-colored waxy papules ranging in size from 0.5 to 1.2 cm.
A morphologic variant of dermatofibrosarcoma protuberans characterized by the presence of areas of myofibroblastic differentiation.
A morphologic variant of atypical fibroxanthoma characterized by the presence of spindle-shaped fibrohistiocytic cells and a storiform growth pattern.
An undifferentiated pleomorphic sarcoma arising from the skin. It is characterized by the presence of spindle cells in a storiform pattern and histiocytes with abundant cytoplasm.
A rare neurofibroma with epithelioid morphology.
A usually painless, slow growing benign tumor that most often arises from the extremities. It is characterized by the presence of abundant myxoid matrix and small epithelioid neoplastic Schwann cells.
A rare benign genetic skin disease with characteristics of numerous, painless, encapsulated lipomas located in the subcutaneous adipose tissue of the trunk and extremities, with relative sparing of the neck and shoulders. Association with gastroduodenal lipomatosis, brain anomalies or lipomatosis, and refractory epilepsy has been reported.
A morphologic variant of well differentiated liposarcoma characterized by the presence of bland spindle cells and lipoblasts within a myxoid or fibrous stroma.
A benign neoplasm arising from the extraskeletal soft tissues near tendons and joints. It is a well circumscribed tumor characterized by the presence of chondrocytes, a lobulated hyaline cartilage growth pattern, and in some cases calcification.
Extraskeletal myxoid chondrosarcoma is a rare soft tissue neoplasm of chondroblastic origin. The tumors are most commonly found in middle-aged and elderly individuals, are more common among men, and are often detected as deep-seated lesions in the extremities. Despite their relatively low-grade malignancy, recurrence and metastasis may appear many years after the initial diagnosis. Histologic tissue section examination reveals a mixture of cellular and myxoid stromal components (Panagopoulos et al., 2002).
A rare malignant tumor of soft tissue characterized by a bimorphic pattern composed of undifferentiated small round cells and islands of well differentiated hyaline cartilage.
An angiomyxoma arising from the dermis or subcutaneous tissues. It may recur following resection.
A low grade, late-metastasizing variant of fibrosarcoma characterized by alternating fibrous and myxoid areas and a whorling growth pattern. The neoplastic cells have a spindle morphology, and lack hyperchromasia or significant nuclear atypia. Approximately 40% of cases show the focal presence of collagen rosettes. A t(7;16)(q33;p11) translocation has been identified in the majority of cases, associated with the presence of FUS-CREB3L2 fusion protein. Rare cases carry the t(11;16)(p11;p11) translocation which is associated with the presence of the FUS-CREB3L1 fusion protein.
A diffuse large B-cell lymphoma that arises from the skin. This category includes primary cutaneous diffuse large B-cell lymphoma, leg type, and primary cutaneous diffuse large B-cell lymphoma, other, which includes primary cutaneous intravascular large B-cell lymphoma and primary cutaneous T-cell/histiocyte-rich large B-cell lymphoma.
A cutaneous necrobiotic disorder characterized by firm, yellow plaques or nodules, often in a periorbital distribution. It is often accompanied by an elevated ERYTHROCYTE SEDIMENTATION RATE; LEUKOPENIA; and MONOCLONAL GAMMOPATHY (IgG-kappa type) and systemic involvement.
A Spitz nevus associated with fibrous stroma formation.
An insidious poorly circumscribed neoplasm arising from the soft tissues outside the abdomen. It is characterized by the presence of elongated spindle-shaped fibroblasts, vascular collagenous stroma formation, and an infiltrative growth pattern.
An acute inflammation of the umbilical cord. It is characterized by the presence of polymorphonuclear cells migrating from the fetal umbilical cord vessels through the umbilical cord towards the bacteria containing amniotic fluid.
A group of acute myeloid leukemias characterized by recurrent genetic abnormalities, mainly balanced translocations. (WHO, 2001)
A rare malignant embryonal neoplasm characterized by the presence of small cells which resemble the cells of classic medulloblastoma and a minor population of melanin-forming neuroepithelial cells. It usually has an unfavorable clinical course.
A type of blepharitis that affects the meibomian glands and meobomian gland orifices. This abnormality can be associated with a spectrum of appearances ranging from meibomian seborrhoea (foaming meibomian gland secretions) and meibomianitis (inflamed meibomian glands), to chalazia. [ORCID:0000-0003-0986-4123]
A number sign (#) is used with this entry because the Avellino type of corneal dystrophy (CDA) is caused by mutation in the gene encoding keratoepithelin (TGFBI; 601692). Several other forms of autosomal dominant corneal dystrophy are caused by mutation in this gene, which maps to chromosome 5q31.
Care providers in the perioperative environment provide health services within their legal and ethical scope of practice. Health care professionals are responsible for meeting legal, institutional, professional, and regulatory standards.
Injury to perineum involving anal sphincter complex and internal anal sphincter and anal epithelium. (reVITALize)
Congenital central hypoventilation syndrome (CCHS) is a rare disorder of respiratory and autonomic regulation. It is typically characterized by a classic presentation in newborns and, rarely, a milder later-onset (LO-CCHS) presentation in toddlers, children, and adults. Classic CCHS presents in newborns as: Apparent hypoventilation with monotonous respiratory rates and shallow breathing either during sleep only or while awake as well as asleep; Autonomic nervous system dysregulation (ANSD); and In some individuals, altered development of neural crest-derived structures (i.e., Hirschsprung disease) and/or tumors of neural crest origin (neuroblastoma, ganglioneuroma, and ganglioneuroblastoma). Individuals with CCHS who have been diagnosed as newborns and ventilated conservatively and consistently throughout childhood have now reached the age of 20 to 30 years; they are highly functional and live independently. LO-CCHS manifests as nocturnal alveolar hypoventilation and mild ANSD. Individuals with LO-CCHS who were not identified until age 20 years or older have now reached the age of 30 to 55 years.
A type of transposition of the great arteries (TGA) in which aorta is in front of and primarily to the left of the pulmonary artery.
A cyanotic congenital cardiovascular abnormality characterized by the transposition of the aorta and the pulmonary artery.
A morphologic finding indicating the presence of dysplastic changes in the transitional cell epithelium of the urinary tract.
A common ocular motility disorder characterized by vertical incomitance of the eyes in lateral gaze. In primary inferior oblique muscle overaction, an upshoot of the adducting eye occurs when gaze is directed into the field of action of the inferior oblique muscle, producing a greater upward excursion of the adducted eye than of the abducted eye. [ORCID:0000-0003-0986-4123, PMID:11545636]
An ocular motility abnormality characterized by an overacting superior oblique muscle resulting to vertical incomitance of the eyes in lateral gaze. On examination, this is commonly seen as a downshoot of the adducting eye occuring when gaze is directed into the field of action of the inferior oblique muscle, producing a greater downward excursion of the adducted eye than of the abducted eye. [ORCID:0000-0003-0986-4123, PMID:11545636]
The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290). Genetic Heterogeneity of Fetal Akinesia Deformation Sequence FADS2 (618388) is caused by mutation in the RAPSN gene (601592), FADS3 (618389) is caused by mutation in the DOK7 gene (618389), and FADS4 (618393) is caused by mutation in the NUP88 gene (602552). As mutations in the MUSK, RAPSN, and DOK7 genes have been associated with congenital myasthenic syndromes (see, e.g., CMS1A, 601462), the disorders in these patients likely represent extreme phenotypes of CMS (Vogt et al., 2009).
A generalized or disseminated form of pagetoid reticulosis. Some authors consider it to be a primary cutaneous aggressive epidermotrophic CD8+ T-Cell lymphoma.
Occurence of adrenarche at a later than normal age. Adrenarche normally occurs between six and eight years of age with increased adrenal androgen secretion; its exact biologic role is not well understood. It is accompanied by changes in pilosebaceous units, a transient growth spurt and the appearance of axillary and pubic hair in some children, but no sexual development.
Describes a tumor border with an expanding and smooth configuration.
A Gleason score that is relatively uncommon and indicates a low-grade prostatic adenocarcinoma. The score or sum is estimated by adding the most prevalent and the second most prevalent histopathologic pattern of the malignant infiltrate.
An infection caused by Erysipelothrix rhusiopathiae that is almost wholly restricted to persons who in their occupation handle infected fish, shellfish, poultry, or meat. Three forms of this condition exist: a mild localized form manifested by local swelling and redness of the skin; a diffuse form that might present with fever; and a rare systemic form associated with endocarditis.
Red blood cells remaining after separating plasma from human blood, or collected by apheresis.
A vaccine consisting of DIPHTHERIA TOXOID; TETANUS TOXOID; and whole-cell PERTUSSIS VACCINE. The vaccine protects against diphtheria, tetanus, and whooping cough.
Abnormality of left ventricular contraction, often defined operationally as an ejection fraction of less than 40 percent.
Culture-positive postnatal infections associated with sensorineural hearing loss, including confirmed bacterial and viral (especially herpes viruses and varicella) meningitis.
An infectious process affecting the peripheral nerves.
An acute or chronic infectious process affecting any part of the genitourinary system.
A slowly progressing leukemia characterized by a clonal (malignant) proliferation of maturing and mature myeloid cells or mature lymphocytes. When the clonal cellular population is composed of myeloid cells, the process is called chronic myelogenous leukemia. When the clonal cellular population is composed of lymphocytes, it is classified as chronic lymphocytic leukemia, hairy cell leukemia, or T-cell large granular lymphocyte leukemia.
Term was discontinued in 1997. In 2000, the term was removed from all records containing it, and replaced with ANXIETY DISORDERS, its postable counterpart.
X-linked severe combined immunodeficiency (X-SCID) is a combined cellular and humoral immunodeficiency caused by a hemizygous pathogenic variant in IL2RG. In typical X-SCID lack of IL2RG function results in near-complete absence of T and natural killer (NK) lymphocytes and nonfunctional B lymphocytes. X-SCID is almost universally fatal in the first two years of life unless reconstitution of the immune system is achieved through bone marrow transplant or gene therapy. In the absence of family history of X-SCID and prior to newborn screening for X-SCID, most males with typical X-SCID come to medical attention between ages three and six months with failure to thrive, oral/diaper candidiasis, absent tonsils and lymph nodes, recurrent infections, infections with opportunistic organisms such as Pneumocystis, and persistence of infections despite conventional treatment. Additional common features include rashes, diarrhea, cough and congestion, fevers, pneumonia, sepsis, and other severe bacterial infections. Males with atypical X-SCID may have immune dysregulation and autoimmunity associated with rashes, gastrointestinal malabsorption, and short stature.
A rare, rapidly progressing interstitial lung disorder characterized by diffuse and bilateral alveolar damage. Patients present with sudden onset of dyspnea and rapid development of respiratory failure. Management is supportive and hospitalization and mechanical ventilation are usually required.
Nonfilarial, noninfective, usually crystalline blockage of the limb lymphatics, almost always affecting the lower limbs and especially the feet.
Platelet-type von Willebrand disease, also known as pseudo-von Willebrand disease, is an autosomal dominant bleeding disorder characterized by abnormally enhanced binding of von Willebrand factor by the platelet glycoprotein Ib (GP Ib) receptor complex. Hemostatic function is impaired due to the removal of VWF multimers from the circulation (Murata et al., 1993). Miller (1996) gave a comprehensive review of the disorder.
Obesity caused by caloric intake greater than caloric expenditures.
Blockage of the lacrimal duct. [HPO:probinson]
A type of ectropion associated with orbicularis muscle weakness caused by cranial nerve VII palsy. [ISBN-13:9781416029076, ORCID:0000-0003-0986-4123]
An acute infection of the anterior portion of the eyelid and surrounding tissues.
A chronic autoimmune disorder that belongs to the mucous membrane pemphigoid disorders. It is characterized by bilateral scarring and opacification of the conjunctivae. It presents with pain and burning sensation in the eyes and photophobia. It leads to blindness.
A benign tumor composed of adipose tissue and dense connective tissue usually located near the temporal fornix. [Dutton, Jonathan J., Gregg S. Gayre, and Alan D. Proia. Diagnostic atlas of common eyelid diseases. New York: Informa Healthcare, 2007. Print.]
A finding of partial or decreased ossification, as indicated by reduced stain uptake.
Raynaud phenomenon associated with an underlying autoimmune disorder.
Inflammation at the site of insertion of ligaments, tendons, and other fibrous structures into bone.
An autosomally inherited (generally dominant) coagulation disorder characterized by qualitative abnormalities of the von Willebrand factor (VWF). The mutant VWF causes decreased platelet adhesion due to a selective deficiency of high molecular weight multimers. The decrease in large multimers can be due to a failure to synthesize the multimers ('group 1') or enhanced ADAMTS13-mediated proteolysis of the secreted high molecular weight protein ('group 2').
An autosomally inherited (generally dominant) coagulation disorder characterized by qualitative abnormalities of the von Willebrand factor (VWF). The mutant VWF shows increased affinity to platelet glycoprotein Ib alpha, resulting in increased platelet aggregation, and increased proteolysis of VWF subunits causing a decrease of large VWF multimers; patients often have secondary thrombocytopenia due to platelet consumption.
An autosomally inherited (generally dominant) coagulation disorder characterized by qualitative abnormalities of the von Willebrand factor (VWF). The mutant VWF shows decreased platelet adhesion without a deficiency of high molecular weight multimers; this functional defect is caused by mutations that disrupt VWF binding to platelets or to subendothelium.
An autosomally inherited (generally recessive) coagulation disorder characterized by qualitative abnormalities of the von Willebrand factor (VWF). The mutant VWF shows markedly decreased binding affinity for factor VIII, which can be confused with mild hemophilia A. The phenotype is characterized by a disproportionate decrease in factor VIII compared to VWF.
Pseudocholinesterase deficiency is a condition that results in increased sensitivity to certain muscle relaxant drugs used during general anesthesia, called choline esters. These fast-acting drugs, such as succinylcholine and mivacurium, are given to relax the muscles used for movement (skeletal muscles), including the muscles involved in breathing. The drugs are often employed for brief surgical procedures or in emergencies when a breathing tube must be inserted quickly. Normally, these drugs are broken down (metabolized) by the body within a few minutes of being administered, at which time the muscles can move again. However, people with pseudocholinesterase deficiency may not be able to move or breathe on their own for a few hours after the drugs are administered. Affected individuals must be supported with a machine to help them breathe (mechanical ventilation) until the drugs are cleared from the body.People with pseudocholinesterase deficiency may also have increased sensitivity to certain other drugs, including the local anesthetic procaine, and to specific agricultural pesticides. The condition causes no other signs or symptoms and is usually not discovered until an abnormal drug reaction occurs.
Congenital sucrase-isomaltase deficiency is a disorder that affects a person's ability to digest certain sugars. People with this condition cannot break down the sugars sucrose and maltose. Sucrose (a sugar found in fruits, and also known as table sugar) and maltose (the sugar found in grains) are called disaccharides because they are made of two simple sugars. Disaccharides are broken down into simple sugars during digestion. Sucrose is broken down into glucose and another simple sugar called fructose, and maltose is broken down into two glucose molecules. People with congenital sucrase-isomaltase deficiency cannot break down the sugars sucrose and maltose, and other compounds made from these sugar molecules (carbohydrates).Congenital sucrase-isomaltase deficiency usually becomes apparent after an infant is weaned and starts to consume fruits, juices, and grains. After ingestion of sucrose or maltose, an affected child will typically experience stomach cramps, bloating, excess gas production, and diarrhea. These digestive problems can lead to failure to gain weight and grow at the expected rate (failure to thrive) and malnutrition. Most affected children are better able to tolerate sucrose and maltose as they get older.
A disorder characterized by the progressive loss of function and/or structure of the affected tissues.
Disorders caused by nutritional imbalance, either overnutrition or undernutrition, in the FETUS in utero.
Accumulation of fluid in the peritoneal cavity during the fetal period.
A respiratory system disorder that occurs during the neonatal period. A representative example is the respiratory distress syndrome.
A sleep disorder (insomnia, hypersomnia, or parasomnia) for which there is strong evidence that the disorder is etiologically linked to the direct physiological effects of a substance (i.e., a drug of abuse, a medication, or toxin exposure).
Reversible disturbances of consciousness, attention, cognition and perception that develop over a short period of time, and which last less than 3 months.
The position of the fetus in the uterus.
Past record of an individual's working life, including periods of unemployment.
Measure of how well someone performs given tasks at their place of work.
The first part of the fetus that is visible at the cervical opening during delivery.
A newborn reflex that is characterized by flexion of the toes when the sole of the foot is stroked.
Well-demarcated area(s) of partial or complete depigmentation in the macula, reflecting atrophy of the retinal pigment epithelium with associated retinal photoreceptor loss.
Circumscribed morphea in which the lesions are restricted to the skin and the immediately underlying subcutaneous tissues.
A condition in which there are visceral manifestations of systemic sclerosis without any cutaneous findings.
The occurrence of arthritis after infection with group A streptococcus. It is non-migratory, protracted in course, and poorly responsive to anti-inflammatory agents. (from Textbook of Pediatric Rheumatology, 6th ed. Cassidy, Petty, Laxer, and Lindsley)
A benign or malignant neoplasm that affects the sternum.
A benign or malignant neoplasm that affects the structures of the axilla. Representative examples include axillary lipoma, axillary lymph node lymphoma, and metastatic carcinoma to the axillary lymph nodes.
A benign or malignant neoplasm that affects the structures of the chest wall. Representative examples include chest wall lipoma and chest wall lymphoma.
A cyst composed of maxillary sinus epithelium along a surgical line of entry
Idiopathic interstitial pneumonia characterized by chronic inflammation and fibrosis in the interstitial lung tissue. It includes cases that cannot be classified into one of the other types of idiopathic interstitial pneumonia.
A benign or malignant neoplasm that affects the epiglottis.
A benign or malignant neoplasm that arises from the hilar region of the lung.
The presence of a localized dilatation or ballooning of a cerebral artery.
A benign or malignant neoplasm that affects the endocardium.
A benign or malignant neoplasm that affects the myocardium.
A benign or malignant neoplasm that affects the inner layer of the pericardium.
Congenital portal-systemic shunt in which at least some portal blood perfuses the liver
The presence of an altered number of of teeth.
A congenital defect characterized by the absence of one or more permanent teeth, including oligodontia, hypodontia, and adontia of the of permanent teeth. [HPO:probinson]
Congenital small optic disc with normal visual function
Noncarious lesion, where tooth is fatigued, flexed, and deformed by biomechanical loading of tooth, primarily at the cervical region. Usually wedge-shaped lesions with sharp-line angles, but sometimes circular invaginations on occlusal surfaces.
A fibroma of the gums with calcification and possibly ossification
Disorders characterized by eye movement abnormalities that are the result of brain, cranial nerve, or neuromuscular junction dysfunction
A non-neoplastic or neoplastic disorder that affects structures of the skull.
A non-neoplastic or neoplastic disorder that affects the structures of the axilla. Representative examples include axillary lymphadenitis, axillary lipoma, and metastatic carcinoma to the axillary lymph nodes.
An infectious or non infectious disorder characterized by signs and symptoms derived from focal or extensive tissue infiltration by acute (e.g., polymorphonuclear) or chronic (e.g., lymphocytic-plasmacytic) inflammatory cells. Representative examples of infectious disorders include viral infections, bacterial infections, and parasitic infections. Representative examples of non-infectious inflammatory disorders include inflammatory bowel disease and inflammatory polyps.
A person becomes a claimant under a motor vehicle accident insurance because of a motor vehicle accident related health condition or injury.
Imaging results obtained through a radiology procedure.
Complex activities performed to support basic life skills
A response indicating that an individual can transfer independently of help from others.
An inhalation reflex stimulated by an irritation of the mucous membrane of the nose
Symptoms, physical examination results, and/or laboratory test results related to the integumentary system.
An anomaly of the wave-like muscle contractions of the digestive tract.
Distention of the abdomen associated with a feeling of fullness.
An elevated concentration of circulating cholesterol esters, which are fatty acid esters of cholesterol and make up about two-thirds of total plasma cholesterol. [https://www.ncbi.nlm.nih.gov/mesh/68002788]
intermediate in the Krebs' cycle; also produced from glutamate in amino group transfer reactions and by oxidative deamination.
3-hydroxyacyl-CoA dehydrogenase deficiency is an inherited condition that prevents the body from converting certain fats to energy, particularly during prolonged periods without food (fasting).Initial signs and symptoms of this disorder typically occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, and lack of energy (lethargy). Affected individuals can also have muscle weakness (hypotonia), liver problems, low blood sugar (hypoglycemia), and abnormally high levels of insulin (hyperinsulinism). Insulin controls the amount of sugar that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-CoA dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden death. This condition may explain some cases of sudden infant death syndrome (SIDS), which is defined as unexplained death in babies younger than 1 year.Problems related to 3-hydroxyacyl-CoA dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
A reduction in aldehyde oxidase activity.
Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). The most prevalent cause of thyroid dyshormonogenesis is TPO deficiency (Park and Chatterjee, 2005). Defects in TPO cause a severe form of congenital hypothyroidism characterized by a complete and immediate release of accumulated radioiodide from the thyroid after sodium perchlorate administration (Bakker et al., 2000). This release of radioiodide represents total iodine organification defect (TIOD), a disruption of the process by which iodide present in the thyroid is oxidized by hydrogen peroxide and bound to tyrosine residues in thyroglobulin (TG; 188450) to form iodotyrosine.
A deficiency in an enzyme that promotes reduction of an organic compound.
Transaldolase deficiency is a rare inborn error of pentose metabolism. Typical features include intrauterine growth restriction, triangular vase, loose wrinkly skin at birth, and development of progressive liver failure (summary by Lee-Barber et al., 2019).
SHPK deficiency is an autosomal recessive inborn error of metabolism characterized by increased urinary erythritol and sedoheptulose. Additional phenotypic consequences of this deficiency are unclear (summary by Wamelink et al., 2015).
D-glyceric aciduria is a rare autosomal recessive metabolic disorder with a highly variable phenotype. Some patients have an encephalopathic presentation, with severe mental retardation, seizures, microcephaly, and sometimes early death, whereas others have a mild phenotype with only mild speech delay or even normal development (summary by Sass et al., 2010).
An autosomal recessive lysosomal storage disease caused by mutation(s) in the HYAL1 gene, encoding hyaluronidase-1. It is characterized by short stature and hyaluronidase deficiency.
Beta-ureidopropionase deficiency is a rare autosomal recessive inborn error of metabolism due to a defect in pyrimidine degradation. Less than 10 patients have been reported, and the phenotype can range from severe neurologic involvement with mental retardation and seizures to normal neurologic development (Yaplito-Lee et al., 2008).
AADC deficiency is an autosomal recessive inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency (Abeling et al., 2000). The disorder is clinically characterized by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction, usually beginning in infancy or childhood (summary by Brun et al., 2010).
A rare, autosomal dominant, inherited disorder caused by mutation of the ENO1 gene. It is associated with spherocytic hemolytic anemia, exercise-induced myalgia and weakness.
Deficiency of maleylacetoacetate isomerase (MAAID) is characterized by mild elevations in succinylacetone in blood and urine, usually identified by newborn screening. Liver function and coagulation are normal. MAAID is differentiated from hepatorenal tyrosinemia (TYRSN1; 276700), which is also identified by hypersuccinylacetonemia on newborn screening but is a severe disorder with hepatic failure, renal tubulopathy, rickets, and porphyria-like neurologic crises. MAAID and TYRSN1 are caused by mutations in genes encoding the penultimate and ultimate enzymes, respectively, in the phenylalanine and tyrosine degradation pathway (summary by Yang et al., 2017).
A decreased rate of glucose-6-phosphate isomerase activity.
A rare, autosomal recessive, inherited disorder caused by mutation of the BPGM gene. It is characterized by hemolytic anemia and splenomegaly.
Symptoms, physical examination results, and/or laboratory test results related to the urinary system.
The beginning of development of the breasts in the female. [GOC:curators, PMID:19117864]
Symptoms, physical examination results, and/or laboratory test results related to the immune system.
The process of hematopoiesis occurring outside of the bone marrow (in the liver, thymus, and spleen) in the postnatal organisms.
Symptoms, physical examination results, and/or laboratory test results related to the hematopoietic system.
Autosomal recessive inheritance of the Lutheran null blood group phenotype is extremely rare, and has been reported in only 5 individuals. There is no obvious associated clinical or hematologic pathology, and all patients have been identified through identification of anti-Lu3 antibodies in their serum (Karamatic Crew et al., 2007). The Lutheran inhibitor blood group phenotype (In(Lu); 111150) is characterized phenotypically by the apparent absence of the Lu antigen on red blood cells during serologic tests, i.e. Lu(a-b-). Since it is inherited as an autosomal dominant trait, it was initially postulated to result from an inhibitor of the Lu antigen. However, Singleton et al. (2008) found that the phenotype results from a mutation in the transcription factor KLF1 that regulates expression of the BCAM gene. These 2 forms of Lutheran absence on red blood cells can be differentiated both by the pedigree and by serologic studies. An X-linked recessive form (309050) has been rarely reported.
An aggressive non-Hodgkin B-cell lymphoma composed of large cells, presenting as a serous effusion without detectable tumor masses. It is universally associated with human herpes virus 8 (HHV-8)/Kaposi sarcoma herpes virus (KSHV) [HHV-8/KSHV]. It mostly occurs in the setting of immunodeficiency; most cases have been reported in HIV positive patients. The most common sites of involvement are the pleural, pericardial, and peritoneal cavities. The prognosis is extremely unfavorable.
A large B-cell non-Hodgkin lymphoma arising in the mediastinum. Morphologically it is characterized by a massive diffuse lymphocytic proliferation associated with compartmentalizing fibrosis. Response to intensive chemotherapy, with or without radiotherapy, is usually good. (WHO, 2001)
The most frequent type of lymphoblastic lymphoma. It comprises approximately 85-90% of cases. It is more frequently seen in adolescent males. It frequently presents with a mass lesion in the mediastinum. Pleural effusions are common. (WHO, 2001)
The most frequent type of acute lymphoblastic leukemia. Approximately 75% of cases occur in children under six years of age. This is a good prognosis leukemia. In the pediatric age group the complete remission rate is approximately 95% and the disease free survival rate is 70%. Approximately 80% of children appear to be cured. In the adult age group the complete remission rate is 60-85%. (WHO, 2001)
A myelodysplastic/myeloproliferative disorder characterized by myelodysplasia associated with bone marrow and peripheral blood patterns similar to CHRONIC MYELOID LEUKEMIA, but cytogenetically lacking a PHILADELPHIA CHROMOSOME or bcr/abl fusion gene (GENES, ABL).
An acute myeloid leukemia arising de novo and not as a result of treatment. It is characterized by the presence of myelodysplastic features in at least 50% of the cells of at least two hematopoietic cell lines. Patients often present with severe cytopenia.
An acute myeloid leukemia with t(8;21)(q22; q22.1) giving rise to RUNX1/RUNX1T1 fusion transcript and showing maturation in the neutrophil lineage. The bone marrow and the peripheral blood show large myeloblasts with abundant basophilic cytoplasm, often containing azurophilic granules. This type of AML is associated with good response to chemotherapy and high complete remission rate.
Acute myeloid leukemias, myelodysplastic syndromes, and myelodysplastic/myeloproliferative neoplasms arising as a result of the mutagenic effect of chemotherapy agents and/or radiation that are used for the treatment of neoplastic or non-neoplastic disorders.
A rare, highly aggressive, Epstein-Barr virus-associated leukemia, also known as aggressive NK-cell leukemia/lymphoma; it may represent the leukemic counterpart of nasal type extranodal NK/T-cell lymphomas. It affects primarily teenagers and young adults. It is characterized by the systemic proliferation of NK cells in the peripheral blood, bone marrow, liver, and spleen.
A clonal hematopoietic stem cell disorder, characterized by proliferation in the bone marrow of one or more of the myeloid (i.e., granulocytic, erythroid, megakaryocytic, and mast cell) lineages. It is primarily a neoplasm of adults. (WHO 2008)
A myelodysplastic syndrome characterized by a deletion between bands q31 and 33 on chromosome 5. The number of blasts in the bone marrow and blood is <5%. The bone marrow is usually hypercellular or normocellular with increased number of often hypolobated megakaryocytes. The peripheral blood shows macrocytic anemia. This syndrome occurs predominantly but not exclusively in middle age to older women. The prognosis is good and transformation to acute leukemia is rare. (WHO, 2001)
A myelodysplastic syndrome caused by chemotherapy and/or radiotherapy.
A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.
Susceptible to life-threatening, uninhibited response of the sympathetic nervous system post-spinal shock, in an individual with spinal cord injury or lesion at the 6th thoracic vertebra (T6) or above (has been demonstrated in patients with injuries at the 7th thoracic vertebra [T7] and the 8th thoracic vertebra [T8]), which may compromise health.
Reduced amount of the thyroid-stimulating hormone (TSH), which is produced by the anterior pituitary gland and stimulates the function of the thyroid gland.
An elevation above normal limits of the concentration of estradiol in the circulation.
An elevated concentration of glucagon in the blood circulation.
A reduced concentration of glucagon in the blood circulation.
A laboratory test result which indicates decreased levels of fibrinogen in a biological specimen.
A general term that refers to atypical hyperplastic proliferations of the epithelial cells in the breast parenchyma. Examples include atypical ductal hyperplasia, atypical lobular hyperplasia, and columnar cell hyperplasia with atypia.
Recurrent or persistent pain that has lasted at least 3 months, and that significantly affects daily functioning or well-being.
Underdevelopment of the optic disc, that is of the optic nerve head, where ganglion cell axons exit the eye to form the optic nerve.
Any ventricular septal defect (VSD) that does not restrict flow across it sufficiently to generate a pressure gradient between the two sides of the VSD.
An abnormal localized widening (dilatation) of the aortic root. []
The non-affirmative response to a question.
Any agent that inhibits the enzyme alpha-glucosidase located in the intestines. This prevents the breakdown of complex carbohydrates to glucose and other monosaccharides, which results in decreased intestinal absorption of monosaccharides.
A carcinoma that arises from the squamous epithelium of the exocervix.
A carcinoma of the larynx that arises from the subglottic area.
A carcinoma of the larynx that arises from the supraglottic area.
A score assigned to a biopsy sample based on the appearance of nuclei in a tumor.
A bacterial, fungal or viral infectious process affecting the scrotum.
A response indicating that an individual cannot do something.
Something not easily done, accomplished, comprehended, or solved.
A syndrome characterized by orthostatic intolerance resulting in tachycardia, often accompanied by a decrease in the blood pressure. It occurs when individuals change from the supine position to an upright position. Other signs and symptoms include lightheadedness, fainting, fatigue and muscle weakness.
A form of spastic cerebral palsy affecting the lower half of the body, including both legs.
Rupture of the fibrous strands connecting the ciliary body and the crystalline lens of the eye.
Vaccines or candidate vaccines used to prevent infection with WEST NILE VIRUS.
This anomaly, also known as Mittendorf dot, is a benign, nonprogressive recognizable lesion that does not cause visual impairment. However, it can resemble a pathological congenital or acquired cataract lesion which may enlarge and cause visual impairment. The dot appears as a black speck that ranges in size from the dot made by a sharp pencil point to the size of a poppy seed. It is usually well defined, although occasionally there may be irregular, fine lines radiating outward from the dot.
protozoan infection found in animals and man; caused by several different genera of Coccidia.
Describes the morphologic appearance where a tumor meets the adjacent tissue.
The distance of the closest surgical margin from tumor after surgical resection of the tumor. The closest distance between a tumor and its resection margin has prognostic significance.
A soft tissue mesenchymal tumor with perivascular epithelioid cell differentiation. Representative examples include angiomyolipoma, clear cell-sugar-tumor of the lung, and lymphangioleiomyomatosis.
T-cell immune response with diffuse perivillous fibrin deposition associated with intrauterine growth restriction, pre-term birth and recurrent fetal loss.
Thanatophoric dysplasia characterized by a normally shaped skull and curved femurs. It is the most common type of thanatophoric dysplasia.
Thanatophoric dysplasia (TD) is a short-limb dwarfism syndrome that is usually lethal in the perinatal period. TD is divided into type I, characterized by micromelia with bowed femurs and, uncommonly, the presence of cloverleaf skull deformity (Kleeblattschädel) of varying severity; and type II, characterized by micromelia with straight femurs and uniform presence of moderate-to-severe cloverleaf skull deformity. Other features common to type I and type II include: short ribs, narrow thorax, macrocephaly, distinctive facial features, brachydactyly, hypotonia, and redundant skin folds along the limbs. Most affected infants die of respiratory insufficiency shortly after birth. Rare long-term survivors have been reported.
Sponastrime dysplasia is a rare autosomal recessive bone disorder. Radiographic findings include abnormal vertebral bodies with age-dependent changes, and striations of the metaphyses, scoliosis, and retarded ossification of the carpal bones. Physical features include severe short stature, lumbar lordosis, midface hypoplasia, frontal bossing, and a depressed nasal root (summary by Cooper et al., 2000).
Hyperparathyroidism in an infant less than one month a=of age that resolves spontaneously.
A rare benign soft tissue neoplasm characterized by the presence of an abundant collagenous or myxocollagenous matrix, spindle-shaped, and stellate-shaped fibroblasts. It usually presents as an asymptomatic, slowly growing subcutaneous mass. The most common sites of involvement are the upper arm, shoulder, and lower limb.
An adenomyoma characterized by the presence of marked glandular architectural complexity.
A neuroendocrine carcinoma of the prostate gland with unfavorable prognosis, composed of small cells containing neurosecretory granules. Approximately half of the cases show a mixture of small cells and adenocarcinoma cells.
A pre-cancerous, non-invasive pancreatic epithelial neoplasm that arises from and is confined to the pancreatic ducts. It is a papillary or flat neoplasm that usually measures less than 5 mm in diameter.
A carcinoma that arises from the pancreas showing a mixture of ductal and neuroendocrine malignant cells in both the primary tumor and in the metastatic sites.
Any structural anomaly of mast cells, which are found in almost all tissues and contain numerous basophilic granules and are capable of releasing large amounts of histamine and heparin upon activation.
An aggressive, high grade adenocarcinoma that arises from the salivary glands. It usually affects elderly males and presents as a rapidly enlarging mass. It metastasizes to regional lymph nodes and distant anatomic sites.
A benign epithelial neoplasm of the skin. It presents as a papular or nodular lesion. Morphologically, it is characterized by the presence of hyperkeratosis, acanthosis, papillomatosis, and prominent acantholysis.
A category of clonal hematopoietic disorders that have both myelodysplastic and myeloproliferative features at the time of initial presentation.
A myelodysplastic syndrome characterized by bi-cytopenia or pancytopenia, dysplastic changes in 10% or more of the cells in two or more of the myeloid cell lines, and 15% or more ring sideroblasts in the bone marrow. (WHO, 2001)
An acute leukemia in which the blasts lack sufficient evidence to classify as myeloid or lymphoid or they have morphologic and/or immunophenotypic characteristics of both myeloid and lymphoid cells. (WHO, 2001)
A neoplasm of lymphoblasts committed to the T-cell lineage, typically composed of small to medium-sized blast cells. When the neoplasm involves predominantly the bone marrow and the peripheral blood, it is called T acute lymphoblastic leukemia. When it involves nodal or extranodal sites it is called T lymphoblastic lymphoma. (WHO, 2001)
A clonal B-cell lymphoproliferative disorder arising as a result of post-transplant immunosuppression therapy. It is characterized by destructive infiltration of lymph nodes and extranodal sites by a polymorphic B-cell infiltrate composed of small and medium sized lymphocytes, immunoblasts, and plasma cells. In some cases, reduction of the immunosuppression therapy may lead to regression of the lesions. In other cases the lesions may progress to lymphoma.
An anaplastic large cell lymphoma limited to the skin at the time of diagnosis. Most patients present with solitary or localized skin lesions, which may be tumors, nodules or papules. The t(2;5) translocation that is present in many cases of systemic anaplastic large cell lymphoma, is not found in this disease. (WHO, 2001)
An aggressive immature hematologic neoplasm formerly known as blastic NK cell lymphoma, composed of cells with a lymphoblast-like morphology. Recent evidence suggests derivation from a plasmacytoid monocyte. Patients present with cutaneous tumors and bone marrow involvement.
A dendritic cell neoplasm that does not fall into well-defined categories or shows hybrid features.
A disorder characterized by systemic infiltration of internal organs by aggregates of neoplastic mast cells and the presence of a clonal non-mast cell hematologic neoplasm (e.g., myelodysplastic syndrome, chronic myeloproliferative disorder, acute myeloid leukemia, and lymphoma).
Ocular pain which may be very intense, accompanied by corneal epithelium damage, conjunctival injection, lacrimation, blepharospasm, photophobia and hazy vision following corneal edema caused by overwear of contact lenses, principally the PMMA type.
The perioperative plan of care reflects the uniqueness of each patient, and social or economic status, personal attributes of lifestyle, culture, ethnicity, or level of health are considered and respected and reflected in the nursing plan of care.
The patient's personal privacy, confidentiality, and security within the perioperative environment are maintained. This includes: maintaining the patient's privacy; securing patient records, personal belonging, and valuables; entering appropriate and accurate information into the patient record; and maintaining confidentiality of patient information.
The treatment and care received is consistent with an individualized perioperative plan of care.
The patient receives consistent and comparable care regardless of the setting and from the appropriate care providers. The patient's care is delivered in a nondiscriminatory and nonjudgmental manner according to published legal, facility, professional, and regulatory standards.
Patient and designated support person communicates an understanding of pain assessment methods and the plan for pain management, including knowledge of pharmacologic and non-pharmacologic methods of pain management and the need to report pain in a timely manner.
A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).
A deformity of foot and ankle that has different subtypes that are talipes equinovarus, talipes equinovalgus, talipes calcaneovarus and talipes calcaneovalgus.
Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia.
A combination preparation of a synthetic angiotensin-converting enzyme (ACE) inhibitor prodrug and a diuretic thiazide, with antihypertensive activity. Enalapril maleate is de-esterified within the cells into its active form enalaprilat that inhibits ACE, thereby prevents the formation of angiotensin II, and blocks angiotensin II mediated activities, including vasoconstriction and stimulation of aldosterone synthesis and secretion, which regulates extracellular sodium concentration. Hydrochlorothiazide inhibits electrolytes reabsorption via binding to Na-Cl cotransporter on the renal distal tubular, thereby increasing excretion of sodium, potassium, chloride, bicarbonate and water. Both agents lead to a reduction in blood pressure.
Having a substantial blood pressure lowering capability, Amlodipine Besylate Benazepril Hydrochloride contains a dihydropyridine calcium blocker (amlodipine) and an angiotensin-converting enzyme (ACE) inhibitor (benazepril). A long-acting calcium channel antagonist, Amlodipine inhibits transmembrane calcium influx into vascular smooth muscle. Blocking ACE, Benazepril decreases vasopressive plasma angiotensin II. (NCI04)
A combination of a synthetic antihypertensive phenoxy-2-propanol derivative and a diuretic thiazide used for hypertension, Bisoprolol Fumarate Hydrochlorothiazide acts as a selective beta-1 (cardio) adrenergic antagonist, without membrane stabilizing activity or intrinsic sympathomimetic activity. Hydrochlorothiazide affects renal tubular electrolyte reabsorption, increasing excretion of sodium and chloride. (NCI04)
A topical combination preparation containing the sulfate salt form of the aminoglycoside antibiotic neomycin, the sulfate salt form of the polypeptide antibiotic polymyxin B, and the glucocorticoid dexamethasone, with antimicrobial, anti-infective and anti-inflammatory activities. Upon topical application, neomycin irreversibly binds to the bacterial 30S ribosomal subunit, thereby preventing mRNA from binding, causing both misreading and the inhibition of protein synthesis. Polymyxin B binds, with its positively charged amino groups, to negatively charged phospholipids in the outer cell membrane of Gram-negative bacteria, thereby disrupting cell wall integrity and altering the permeability of the bacterial cytoplasmic membrane. Dexamethasone binds to the cytoplasmic glucocorticoid receptor, and this receptor-ligand complex is translocated to the nucleus where it initiates the transcription of genes encoding for anti-inflammatory mediators, such as cytokines and lipocortins.
A combination formulation containing the hydrochloride salt form of the benzodiazepine chlordiazepoxide and the bromide salt form of the quaternary ammonium antimuscarinic clidinium with anxiolytic, sedative and antispasmodic activities. Chlordiazepoxide binds to a specific benzodiazepine-binding site on the gamma-aminobutyric acid (GABA)-A receptor in the central nervous system (CNS). This leads to an increase in the opening of chloride channels, membrane hyperpolarization and increases the inhibitory effect of GABA on the CNS. Clidinium binds to and blocks muscarinic receptors in the gastrointestinal (GI) tract. This leads to a decrease in stomach secretions, GI motility and GI spasms.
Features of tetralogy of Fallot with either rudimentary ridges or the complete absence of pulmonic valve tissue.
Study subjects in COHORT STUDIES whose outcomes are unknown e.g., because they could not or did not wish to attend follow-up visits.(from Dictionary of Epidemiology, 5th ed.)
A morphologic finding indicating the presence of dysplastic glandular epithelial cells in the colonic mucosa. There is no evidence of invasion.
A neoplasm that arises from the glandular epithelium of the small intestine. It is a polypoid or flat circumscribed lesion. Morphologically, it is characterized by a proliferation of neoplastic glandular cells and it is associated with dysplasia. According to the growth pattern, it may be classified as tubular, villous, or tubulovillous.
An adenoma that arises from the colon or rectum. The group of colorectal adenomas includes tubular, villous, and tubulovillous adenomas, traditional serrated adenomas, sessile serrated adenomas/polyps, and familial adenomatous polyposis.
An invasive prostate carcinoma characterized by the presence of squamous differentiation of the malignant cellular infiltrate. There is no evidence of glandular differentiation.
A human papillomavirus-related neoplasm that arises from the vagina. It is characterized by papillomatosis, acanthotic changes, and hyperkeratosis. Koilocytosis is usually present.
An indolent, mature B-cell neoplasm composed of small, round B-lymphocytes. When the bone marrow and peripheral blood are involved, the term chronic lymphocytic leukemia is used. The term small lymphocytic lymphoma is restricted to cases which do not show leukemic involvement of the bone marrow and peripheral blood.
A teratoma that arises from the ovary and is characterized by the presence of tissues derived exclusively from one embryonic germ cell layer.
A discrete abnormal tissue mass that protrudes into the lumen of the small intestine and is attached to the intestinal wall either by a stalk, pedunculus, or a broad base.
An adenoma that arises from the rectum. The group of rectal adenomas includes tubular, villous, and tubulovillous adenomas, traditional serrated adenomas, sessile serrated adenomas/polyps, and familial adenomatous polyposis.
A hamartoma characterized by localized malformation of one or more of the skin appendages; including sweat glands, sebaceous glands, and hair follicles.
A hamartoma (tissue malformation consisting of an abnormal mixture of constitutive components) originating in the skin.
A hamartomatous lesion which is present at birth.
A precancerous neoplastic process characterized by the presence of mild dysplastic cytological changes which are usually present in the lower part of the squamous epithelium. Representative examples include the low grade esophageal squamous intraepithelial neoplasia, low grade cervical squamous intraepithelial neoplasia, low grade vaginal intraepithelial neoplasia, and low grade vulvar intraepithelial neoplasia.
A syndrome characterized by the presence of congenital abnormalities that affect more than one organ or system.
A usually slow growing, subcutaneous nodular neoplasm arising from myopericytes. It is composed of myoid cells arranged in a perivascular growth pattern. The vast majority of cases have a benign clinical course.
A benign hamartomatous lesion composed predominantly of adipose tissue.
Congenital non-progressive ophthalmoplegia with multiple extraocular muscle restrictions. Typically, there is ptosis and variable degrees of restriction of horizontal and vertical eye movements.
Partial fusion of the upper and lower eyelid margins by single or multiple bands of tissue.
Euryblepharon is a congenital eyelid anomaly characterized by horizontal enlargement of the palpebral fissure. The eyelid is shortened vertically compared with the horizontal dimension, with associated lateral canthal malpositioning and lateral ectropion abnormally wide lid opening. [HPO:probinson, pmid:15249382, pmid:15530943, pmid:24719364]
A type of epicanthus in which a primarily upper lid fold is present. [ORCID:0000-0003-0986-4123]
A fold of skin starting at or just below the medial aspect of the lower lid and arching upward to cover, extend in front of and lateral to the medial canthus.
A type of epicanthus in which a medial vertical fold is present between upper and lower lids. [ORCID:0000-0003-0986-4123]
The presence of whitish spots in a ring-like arrangement at the periphery of the iris.
Inherited congenital microcoria, also referred to as congenital miosis, is characterized by bilateral small pupils (diameter less than 2 mm) that result from an underdevelopment of the dilator pupillae muscle of the iris (Holth and Berner, 1923; Simpson and Parsons, 1989). Iris transillumination defects are a constant feature. The pupil dilates poorly or not at all in response to topically administered mydriatic drugs. The disorder is transmitted as an autosomal dominant trait with complete penetrance and is associated with goniodysgenesis and glaucoma (Tawara and Inomata, 1983; Mazzeo et al., 1986; Toulemont et al., 1995).
Nicolaides-Baraitser syndrome (NCBRS) is characterized by sparse scalp hair, prominence of the inter-phalangeal joints and distal phalanges due to decreased subcutaneous fat, characteristic coarse facial features, microcephaly, seizures, and developmental delay / intellectual disability. Seizures are of various types and can be difficult to manage. Developmental delay / intellectual disability (ID) is severe in nearly a half, moderate in a third, and mild in the remainder. Nearly a third never develop speech or language skills.
Abnormal tortuous (i.e., twisted) form of the carotid arteries.
A variant of basal cell carcinoma morphologically characterized by the presence of thin strands of basaloid cells forming a reticulate pattern.
A variant of basal cell carcinoma with the architectural features of a nodular basal cell carcinoma. It is characterized by the formation of keratin (horn cysts) in the center of the tumor islands. Dystrophic calcification is frequently present.
A basal cell carcinoma of the skin that often appears as elevated nodules which may become ulcerated.
A malignant vascular neoplasm arising from blood vessels and lymphatics of the skin.
Linear and whorled hypermelanosis (LWNH) is a benign skin condition characterized by onset in infancy of hyperpigmented regions composed of small light brown spots that coalesce with age and follow the lines of Blaschko on the trunk and limbs. The soles, palms, face, and mucous membranes are spared. The lesions are asymptomatic and progress with age; affected individuals have no accompanying extradermal features. There is no previous history of inflammation on affected areas (summary by Kalter et al., 1988).
A hemangioma characterized by the presence of spindle endothelial cells.
A glomus tumor arising in the finger and usually associated with pain.
A histologically distinctive, cutaneous, benign vascular tumor that is characterized by a solitary or multiple blue-red papules and histologically resembles renal glomeruli.
An intermediate, locally aggressive and rarely metastasizing blood vessel neoplasm. It is characterized by the presence of hobnail endothelial cells and formation of arborizing vascular channels.
An intermediate, locally aggressive and rarely metastasizing blood vessel neoplasm. It is characterized by the presence of spindle, plump, and epithelioid endothelial cells and cellular atypia.
A reactive, painless lesion which is characterized by a pseudosarcomatous proliferation of fibroblasts and myofibroblasts usually in the deep subcutaneous tissue. It occurs mainly around the limb girdles, sacral region, and greater trochanter. It affects mainly elderly patients and sometimes is associated with physical immobility. Local excision is usually curative.
A rhabdoid tumor which arises in the soft tissues. It occurs in infants and children and may be associated with loss of chromosome 22. It is characterized by the presence of cells with a large eccentric nucleus, prominent nucleolus, and abundant cytoplasm.
A chromosomal abnormality in that is characterized by an addition of chromosomes that results in a chromosome number that is not an exact multiple of the haploid number.
An uncommon lipoma characterized by prominent vascularity that invades the surrounding deep tissue.
An adenoma characterized by increased cellularity and nuclear atypia without evidence of vascular or capsular invasion. A representative example is thyroid gland atypical follicular adenoma.
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
The complement pathway consists of a series of over thirty proteins in plasma that are part of the immune response. Activation of the complement system lyses bacterial cells, forms chemotactic peptides (C3a and C5a) attracting immune cells, and increases phagocytotic clearance of infecting cells. Complement can also increase the permeability of vascular walls and cause inflammation. Most complement proteins exist in plasma as inactive precursors that cleave and activate each other in a proteolytic cascade in response to three different mechanisms by which the complement system is activated, the classical pathway, the alternative pathway and the lectin-induced pathway. These three systems are distinct in the initiation of the proteolytic cascade but share most of their components and all three converge in the creation of a C3 convertase that cleaves the C3 complement protein, leading ultimately to the formation of the membrane attack complex, MAC, a pore causing lysis of cells. The classical pathway is activated by the recognition of foreign cells by antibodies bound to the surface of the cells. The alternative and lectin-induced pathways are both antibody independent. Proteolysis is triggered in the alternative pathway by the spontaneous activation of C3 convertase from C3 and is triggered in the lectin-induced pathway by the recognition of carbohydrates on the bacterial cell surface by mannan-binding protein, Mbp. In addition to providing a key part of the response to bacterial infection, the complement system can be involved in the response to fungi, viruses and protists. While activation of the complement system is a key part of the immune system, it must also be kept in check to prevent inappropriate or exaggerated responses. Twelve different proteins have been identified that inhibit complement activation to control the system, including Factor H, Factor I and C1 inhibitor. Deficiencies in components of the complement system have been identified in humans that cause a variety of immune related disorders. C3 deficiency is associated with recurrent bacterial infections, while a lack of C2 can cause antibody-antigen complexes to accumulate and cause the autoimmune disorder systemic lupus erythematosus. People lacking C1 inhibitor have also been identified and found to be prone to uncontrolled complement activation and dangerous swelling through production of C3a and C5a anaphylatoxins. (This definition may be outdated - see the DesignNote.)
A malocclusion in which maxillary incisor and canine teeth project over the mandibular teeth excessively. The overlap is measured perpendicular to the occlusal plane and is also called vertical overlap. When the overlap is measured parallel to the occlusal plane it is referred to as overjet.
A benign skin adnexal tumor of eccrine differentiation.
Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000). Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006). CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970). Genetic Heterogeneity of Developmental Dysplasia of the Hip Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21.
A drug that selectively activates certain subclasses of muscarinic receptors and also activates postganglionic nicotinic receptors. It is commonly used experimentally to distinguish muscarinic receptor subtypes.
A pituitary adenoma which secretes ADRENOCORTICOTROPIN, leading to CUSHING DISEASE.
A locally infiltrating, non-metastasizing angiomyxoma arising from the pelviperineal region. It may recur following resection
A rare circumscribed, non-encapsulated and grossly pigmented nerve sheath tumor. It is composed of cells with the immunophenotypic and electron microscopic features of Schwann cells which contain melanosomes and are positive for melanoma markers. It usually involves spinal nerve roots but may occur in other locations. It may be associated with PRKAR1A gene mutation and Carney complex. Malignant behavior has been reported in a significant number of patients.
crucial, sudden, or decisive point or situation wherein emotional factors predominate.
Provision of liquid nutrition via a closed container system with a rubber like mouthpiece resembling a nipple.
A malignant tumor at the original site of growth.
A HERNIA due to an imperfect closure or weakness of the umbilical ring. It appears as a skin-covered protrusion at the UMBILICUS during crying, coughing, or straining. The hernia generally consists of OMENTUM or SMALL INTESTINE. The vast majority of umbilical hernias are congenital but can be acquired due to severe abdominal distention.
Conditions in which the LIVER functions fall below the normal ranges. Severe hepatic insufficiency may cause LIVER FAILURE or DEATH. Treatment may include LIVER TRANSPLANTATION.
A morphologic variant of embryonal rhabdomyosarcoma arising from organs with a mucosal epithelial surface. It is characterized by the formation of a cambium layer in the affected tissue and polypoid nodules within an abundant myxoid stroma.
A life-threatening disorder characterized by delirium, seizures, and neuromuscular changes.
A finding indicating the absence of balanced proportions between parts of the face.
Eosinophils are a type of white blood cell. They help fight off infections and play a role in your body's immune response. They can also build up and cause inflammation. Normally your blood doesn't have a large number of eosinophils. Your body may produce more of them in response to. -Allergic disorders. -Skin conditions. -Parasitic and fungal infections. -Autoimmune diseases. -Some cancers. -Bone marrow disorders. In some conditions, the eosinophils can move outside the bloodstream and build up in organs and tissues. Treatment of the problem depends on the cause.
A scopolamine derivative and CHOLINERGIC ANTAGONIST that functions as a BRONCHODILATOR AGENT. It is used in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE.
An abrupt onset drug reaction characterized by a red rash that involves the face, neck, and upper torso.
Botulism that is caused by toxin that is produced in a wound contaminated with Clostridium botulinum.
Thyroiditis associated with painless enlargement of the thyroid gland. It occurs more frequently in females and is characterized by alterations between hyperthyroidism and hypothyroidism and the eventual return to normal thyroid gland function.
A rare subtype of renal cell carcinoma arising from the renal tubular epithelium and showing a papillary growth pattern, which typically manifests with haematuria, flank pain, palpable abdominal mass or nonspecific symptoms, such as fatigue, weight loss or fever. Symptoms related to metastatic spread, such as bone pain or persistent cough, are frequently associated since early diagnosis is not common. It is typically multifocal, bilateral, and in most cases sporadic, although different hereditary syndromes may predispose to the development of papillary renal cell carcinoma.
abnormally high globulin content of the blood.
epidemic, highly communicable disease of sudden onset, caused by the epidemic gastroenteritis virus (especially Norwalk agent) which affects all age groups; infection is associated with fever, abdominal cramps, nausea, vomiting, diarrhea, and headache, one or another of which may be predominant.
Disorder caused by the occlusion of the lumen of the peripheral arteries. Causes include atherosclerosis, inflammatory processes, thrombosis, and embolism. The arterial occlusion results in chronic or acute pain usually in the lower limbs due to muscle ischemia.
An abnormality of the placenta, the organ that connects the developing fetus to the uterine wall to enable nutrient uptake, waste elimination, and gas exchange.
Coagulation factor VIII (2351 aa, ~267 kDa) is encoded by the human F8 gene. This protein plays a role in the modulation of coagulation factor IX activity and blood coagulation.
A Swiss multinational pharmaceutical company that is engaged in the development, manufacturing, and marketing of healthcare products.
The hydrochloride salt of palonosetron, a carbazole derivative and a selective serotonin receptor antagonist with antiemetic activity. Palonosetron competitively blocks the action of serotonin at 5-hydroxytryptamine type 3 (5-HT3) receptors located on vagal afferents in the chemoreceptor trigger zone (CTZ), resulting in suppression of chemotherapy-induced nausea and vomiting. The CTZ is located in the area postrema on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle and outside the blood-brain barrier (BBB).
A complex structure that includes isoquinolines joined by a cyclic ester; it is a DNA-binding agent and guanine N2 alkylator derived from the marine tunicate, Ecteinascidia turbinata. Trabectedin is used for the treatment of advanced soft-tissue SARCOMA, after failure of ANTHRACYCLINES or IFOSFAMIDE drug therapy.
Inhibitor of growth protein 1 (422 aa, ~47 kDa) is encoded by the human ING1 gene. This protein is involved in the regulation of the cell cycle.
A synthetic analogue of 9-cis retinoic acid with potential antineoplastic and chemopreventive activities. Retinoid 9cUAB30 binds to and activates retinoid X receptor (RXR) homodimers and/or and retinoic acid receptor (RAR)/RXR heterodimers, which may result in the dissociation of corepressor protein and the recruitment of coactivator protein, followed by transcription of downstream target genes into mRNAs and protein translation. Gene transcription regulated by these transcription factors may result in inhibition of cell proliferation, induction of cell differentiation, and apoptosis of both normal cells and tumor cells.
A water-in-oil emulsion that stimulates the T-cell immune response to antigens and may be used in various types of cancer vaccines. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42976&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42976&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1573"" NCI Thesaurus)
The mesylate salt of an orally active small molecule with antineoplastic and hematopoiesis- stimulating activities. By cleaving N-terminal Xaa-Pro or Xaa-Ala residues, talabostat inhibits dipeptidyl peptidases, such as fibroblast activation protein (FAP), resulting in the stimulation of cytokine and chemokine production and specific T-cell immunity and T-cell dependent activity. This agent may also stimulate the production of colony stimulating factors, such as granulocyte colony stimulating factor (G-CSF), resulting in the stimulation of hematopoiesis. Dipeptidyl peptidases are involved in the activation of polypeptide hormones and chemokines.
An orally bioavailable organoselenium inhibitor of thioredoxin reductase 1 (TrxR1), with potential antineoplastic activity. Upon oral administration, ethaselen specifically binds to the selenocysteine-cysteine redox pair in the C-terminal active site of TrxR1 and inhibits its activity, which may result in growth inhibition and the induction of apoptosis in TrxR1 overexpressing tumor cells. TrxR1, upregulated in many cancer cell types, plays a key role in various redox-dependent cellular pathways, regulates transcription factor activity, inhibits apoptosis, and promotes cell growth and survival.
An agent consisting of chlorin e6, derived from chlorophyll, and L-aspartic acid with photosensitizing activity. After intratumoral activation by light emitting diodes, taporfin sodium forms an extended high energy conformational state that generates singlet oxygen, resulting in free radical-mediated cell death. (NCI04)
Monoclonal recombinant antibody J591 (mAb HuJ591) recognizes the extracellular domain of prostate specific membrane antigen (PSMA), a cell surface peptidase highly expressed by malignant prostate epithelial cells and vascular endothelial cells of numerous solid tumor malignancies. Early results of clinical Phase I and II studies indicate that mAb HuJ591 represents targeted therapy to PSMA and has therapeutic potential in disseminated prostate cancer and other urological and solid tumor malignancies and did not result in a host immune response to the antibody. (NCI)
A drug used to control the amount of sugar in the blood of patients with diabetes mellitus. It is a form of the hormone insulin that is made in the laboratory. Insulin glulisine gets into the blood faster than insulin when it is injected under the skin before or shortly after a meal. It is a type of therapeutic insulin.
A liposomal formulation of the ether lipid 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine with potential antineoplastic activity. TLC ELL-12 induces tumor cell apoptosis via mitochondria- and caspase-mediated mechanisms. Liposomal encapsulation reduces the free agent's hemolytic toxicity. (NCI04)
A substance being studied in the treatment of cancer. It is made by combining interleukin-4 with a bacterial toxin. Interleukin-4 PE38KDEL immunotoxin is a type of recombinant chimeric protein.
A semi-synthetic orally-available taxane derivative with potent antineoplastic properties. DJ-927 binds to tubulin, promoting microtubule assembly and stabilization and preventing microtubule depolymerization, thereby inhibiting cell proliferation. As it represents poor substrate for P-glycoprotein-related drug resistance mechanisms, this agent may be useful for treating multi-drug resistant tumors. DJ-927I is more potent than paclitaxel and docetaxel and is the first oral taxane derivative. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=346914&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=346914&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C37451"" NCI Thesaurus)
An encapsulated accumulation of URINE in the retroperitoneal area. It has the appearance of a cyst (CYSTS). Urinoma is usually caused by URETERAL OBSTRUCTION, renal trauma or perforation of the renal collecting system.
An abnormal pattern of respiration characterized by cycles of respiration that are increasingly deeper then shallower with possible periods of apnea. Affected patients may display a 10 to 20 second episode of hypoventilation or apnea, followed by respiration of increased depth and frequency over the course of about one minute. The cycle repeats every 45 seconds to 3 minutes.
Trichothiodystrophy is a rare autosomal recessive disorder in which patients have brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern, called 'tiger tail banding,' under polarizing microscopy. TTD patients display a wide variety of clinical features, including cutaneous, neurologic, and growth abnormalities. Common additional clinical features are ichthyosis, intellectual/developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections. There are both photosensitive and nonphotosensitive forms of the disorder (summary by Faghri et al., 2008). Sabinas brittle hair syndrome (211390) is another form of nonphotosensitive TTD. For a discussion of genetic heterogeneity of trichothiodystrophy, see 601675.
Acute inflammation of the conjunctiva characterized by pink or red color in the eyes.
Inhibits the activity of prostaglandins.
Abnormally increased serum levels of alkaline phosphatase activity. [HPO:probinson]
A rare, cytologically malignant ameloblastoma that may metastasize.
Age of first menstruation. A risk factor for breast cancer
A nucleoside reverse transcriptase inhibitor analog of cytosine. Elvucitabine has activity against HIV and chronic hepatitis B.
A morphologic finding referring to a tumor that has spread along and infiltrated nerve fibers. The presence of perineural invasion by malignant tumor cells may represent a poor prognostic factor.
A morphologic finding that refers to the replacement of a group of one type of epithelial cells (e.g., glandular epithelial cells) to another type of epithelial cells (e.g., squamous epithelial cells).
Diffuse benign transformation of the hepatic parenchyma into small regenerative nodules with minimal or no fibrosis.
Sporadic nodular enlargement of the thyroid gland that is not associated with changes in thyroid function or malignancy.
A rare congenital disorder of bone resorption characterised by generalised skeletal densification. Bone marrow failure, fractures and visual impairment are the classical features of the disease, which begins in early infancy or in fetal life. It results from the failure of osteoclasts to resorb immature bone. This leads to abnormal bone marrow cavity formation and to the clinical signs and symptoms of bone marrow failure. It is accompanied by hepatosplenomegaly due to compensatory extramedullary hematopoiesis. The disease is heterogeneous. Over 50% of cases are due to mutations in the TCIRG1 gene and another 10% are due to mutations in the CLCN7 gene. A small number of patients have been described with mutations in the OSTM1 gene. Transmission is autosomal recessive.
A rare condition that involves inflammation and necrosis of the walls of the blood vessels; may occur in rheumatoid arthritis.
Polycythemia resulting from an elevated concentration of erythropoietin.
A tumor usually arising in the synovium of joints, bursa or tendon sheath. It is characterized by the presence of mononuclear cells, multinucleated osteoclast-like giant cells, hemosiderin-laden macrophages, foam cells, and an inflammatory infiltrate. According to the growth pattern, it is classified as localized or diffuse.
An acute myeloid leukemia in which the majority of monocytic cells are promonocytes. (WHO, 2001)
A myelodysplastic syndrome defined by 5-9% blasts in the bone marrow, and <5% blasts in the blood. Approximately 25% of cases progress to an acute leukemia. (WHO)
A myelodysplastic syndrome defined by 10-19% blasts in the bone marrow or 5-19% blasts in the blood. Approximately 33% of cases progress to acute leukemia. The prognosis is usually poor.
Bleeding into the epidural space that is not associated with physical trauma.
A melanocytic nevus that is present at birth. It may present as a small macular, papular, or plaque-like lesion or as a large brown to black hairy skin lesion.
A benign tumor made up of mostly myofibroblasts that appears almost exclusively on the digits of the hands and feet, rarely involving the thumb or big toe. The lesion displays a proliferation of bland intradermal spindle cells arranged in whorls, fascicles, or a storiform pattern in a collagenous background of varying degrees. Also usually present are perpendicular tumor cell fascicles that extend to the epidermis. The small intracytoplasmic inclusions are said to appear similar to red blood cells. The inclusion bodies have been shown to be made up of densely packed vimentin and actin filaments. The tumor often causes a dome-shaped elevation of the overlying structures, forming a protuberant or polypoid nodule. The overlying epidermis can display a host of changes, including acanthosis, hyperkeratosis, parakeratosis, rete ridge flattening, entrapment of adnexal structures, and, rarely, ulceration.
An orally active, synthetic structural analogue of N-acetylglutamate (NAG) and carbamoyl phosphate synthetase 1 (CPS 1) activator, with ammonia lowering activity. NAG, which is formed by the hepatic enzyme N-acetylglutamate synthase (NAGS), is an essential allosteric activator of the enzyme carbamoyl phosphate synthetase 1 (CPS 1). CPS 1 plays an essential role in the urea cycle and converts ammonia into urea. Upon oral administration, carglumic acid can replace NAG in NAGS deficient patients and activates CPS 1, which prevents hyperammonaemia.
Compounds that specifically inhibit PHOSPHODIESTERASE 5.
The state of having been made ready or prepared for use or action.
An infectious process in which the bacteria Staphylococcus aureus is present.
A nephrogenic rest found within the renal lobe.
A nephrogenic rest found at the periphery of the renal lobe.
Capacity of a community to collectively problem solve to achieve community goals
Incidence of violent acts compared with local, state, or national values
Community preparedness to respond to a natural or man-made calamitous event
Extent of positive perception of access to nursing staff, supplies, and equipment needed for care
Extent of positive perception of nursing staff's concern for the client
Extent of positive perception of integration of cultural beliefs, values, and social structures into nursing care
Extent of positive perception of nursing staff's knowledge and expertise used in providing care
A male individual who has had his testicles removed.
A female individual who has had her ovaries removed.
Severity of manifested physical or mental tension resulting from factors that alter an existing equilibrium
Severity of manifested apprehension, tension, or uneasiness arising from an identifiable source in a child from 1 year through 17 years of age
Personal actions to maintain proper body alignment and to prevent muscular skeletal strain
Extent of understanding conveyed about safely caring for a child from 1 year through 17 years of age
Extent of understanding conveyed about promotion of a healthy pregnancy and prevention of complications
Extent of understanding conveyed about sexual development and responsible sexual practices
Extent of understanding conveyed about fertility testing and the conditions that affect conception
Extent of understanding conveyed about maternal health in the period following birth of infant
Extent of understanding conveyed about caring for a baby from birth to first birthday
Extent of understanding conveyed about diabetes, its treatment, and the prevention of complications
Extent of understanding conveyed about prevention of unintended pregnancy
Extent of understanding conveyed about maternal health prior to conception to insure a healthy pregnancy
Outcomes that describe an individual's understanding in applying information to optimize health
Extent of understanding conveyed about provision of a nurturing and constructive environment for a child from 1 year through 17 years of age
Extent of understanding conveyed about proper body alignment, balance, and coordinated movement
Extent of understanding conveyed about prevention of falls
Extent of understanding conveyed about maintenance of an ostomy for elimination
Extent of understanding conveyed about heart disease, its treatment, and the prevention of disease progression and complications
Severity of signs and symptoms of injuries to the body
Physical, psychospiritual, sociocultural, and environmental ease with the impending end of life
Severity of adverse physical, emotional, and social responses
Severity of reported adverse physical and emotional responses due to declining hormonal levels
Severity of observed or reported disruptive effects of chronic nausea, retching, and vomiting on daily functioning
Severity of signs and symptoms of nausea, retching, and vomiting
Therapeutic and adverse effects of prescribed medication
Extent to which maternal well-being is within normal limits from conception to the onset of labor
Extent to which maternal well-being is within normal limits from onset of labor to delivery
Evidence that the victim is no longer receiving substandard or omitted care
Extent of healing following physical or psychological abuse that may include sexual or financial exploitation
Capacity of a family to develop strategies for optimal functioning when a member has a chronic illness or disability
Capacity of a family to positively adapt and function following a significant adversity or crisis
Physiologic response to energy-consuming movements with daily activities
Extent to which fetal signs are within normal limits from conception to the onset of labor
Extent to which fetal signs are within normal limits from onset of labor to delivery
Milestones of physical, cognitive, and psychosocial progression by 1 month of age
Ability of muscles to work together voluntarily for purposeful movement
Readiness of a patient to relocate from a health care institution to living independently
Readiness of a patient to relocate from a health care institution to a lower level of supported living
Open, clear tracheobronchial passages for air exchange
Severity of signs and symptoms of internal or external bleeding
Severity of signs and symptoms of excess intracellular and extracellular fluids
Severity of systemic hypersensitive immune response to a specific environmental (exogenous) antigen
Severity of signs and symptoms of infection during the first 28 days of life
Severity of melancholic mood and loss of interest in life events
Severity of manifested apprehension, tension, or uneasiness arising from an identifiable source
Severity of localized hypersensitive immune response to a specific environmental (exogenous) antigen
A malignant tumor that arises from the transitional (urothelial) epithelial cells lining the urinary tract from the renal calyces to the ureteral orifice.
A malignant epithelial tumor with a glandular organization that originates in the large intestine.
A squamous cell carcinoma that arises from the pharynx.
Body Mass Index (kg/m²) equal to or greater than 40 (WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. WHO Technical Report Series 854. Geneva: World Health Organization, 1995).
Barber-Say syndrome is a rare congenital condition characterized by severe hypertrichosis, especially of the back, skin abnormalities such as hyperlaxity and redundancy, and facial dysmorphism, including macrostomia, eyelid deformities, ocular telecanthus, abnormal and low-set ears, bulbous nasal tip with hypoplastic alae nasi, and low frontal hairline (summary by Roche et al., 2010).
A type of asthma in which aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygen-ase 1 (COX-1) exacerbate bronchoconstriction.
Injectable form of risperidone that is encapsulated in MICROSPHERES.
Indicator of paid employment, e.g., letter of hire, contract, employer letter; copy of pay check or pay stub.
Abnormally persistent clusters of embryonal cells, representing microscopic malformations (dysplasias) of the developing kidney.
Resistnace of the extensor muscles of the neck to being bent forwards (i.e., impaired neck flexion) as a result of muscle spasm of the extensor muscles of the neck. Nuchal rigidity is not a fixed rigidity. Nuchal rigidity has been used as a bedside test for meningism, although its sensitivity for this purpose has been debated. [PMID:12060874]
Overall physical, psychological, and social functioning of a school-age child
Overall physical, psychological, social, and spiritual functioning of an adult 18 years or older
Capacity of a family to provide a supportive milieu as characterized by family member relationships and goals
Capacity of family members to maintain cohesion and emotional bonding
General state of well-being of a community or population
Extent of positive perception of information exchanged between client and nursing staff
Extent of positive perception of coordination of care as the client moves from one care setting to another
Extent of positive perception of nursing assistance to achieve mobility and self-care
Extent of positive perception of nursing care to maintain body functions and cleanliness
Extent of positive perception of living environment, treatment environment, equipment, and supplies in acute or long-term care settings
Extent of positive perception of protection of a client's legal and moral rights provided by nursing staff
Extent of positive perception of nursing assistance to cope with emotional issues and perform mental activities
Extent of positive perception of procedures, information, and nursing care to prevent harm or injury
Extent of positive perception of nursing care to relieve symptoms of illness
Extent of positive perception of instruction provided by nursing staff to improve knowledge, understanding, and participation in care
Balance among heat production, heat gain, and heat loss during the first 28 days of life
Severity of patterns of inattention or impulsivity in a child from 1 year through 17 years of age
Safe passage of fluids and/or solids from the mouth to the stomach
Preparation, containment, and posterior movement of fluids and/or solids in the mouth
Safe passage of fluids and/or solids from the mouth to the esophagus
Extent of regeneration of cells and tissues following bone injury
Personal drive and energy to maintain activities of daily living, nutrition, and personal safety
Milestones of physical, cognitive, and psychosocial progression by 5 years of age
Milestones of physical, cognitive, and psychosocial progression from 6 years through 11 years of age
Balance of electrolytes and non-electrolytes in the intracellular and extracellular compartments of the body
Bleeding from the bronchial wall and/or lung parenchyma.
A biphasic neoplasm that arises from the ovary or the testis. It is characterized by the presence of neoplastic germ cells and neoplastic sex cord-stromal cells. It includes the gonadoblastoma and mixed germ cell-sex cord stromal tumor, unclassifiable.
A scotoma (area of diminished vision within the visual field) that surrounds the central fixation point.
An abnormally slow velocity of the saccadic eye movements.
A rare variant of malignant peripheral nerve sheath tumor composed predominantly or exclusively of epithelioid cells.
An electrocardiographic finding of a supraventricular arrhythmia characterized by 3 or more distinct P wave morphologies with an isoelectric baseline, variable PR intervals and no predominant atrial rhythm. The ventricular rate is typically below 100 beats per minute. (CDISC)
A diffuse large B-cell lymphoma variant characterized by the presence of large round, oval, or polygonal cells with bizarre pleomorphic nuclei resembling Hodgkin or Reed-Sternberg cells. It is unrelated to anaplastic large cell lymphoma which is a T-cell non-Hodgkin lymphoma.
A large B-cell lymphoma characterized by the presence of a limited number of scattered neoplastic large B-lymphocytes which are admixed with numerous non-neoplastic T-lymphocytes and frequently histiocytes.
Shprintzen-Goldberg syndrome (SGS) is characterized by: craniosynostosis of the coronal, sagittal, or lambdoid sutures; dolichocephaly; distinctive craniofacial features; skeletal changes (dolichostenomelia, arachnodactyly, camptodactyly, pes planus, pectus excavatum or carinatum, scoliosis, joint hypermobility or contractures and C1/C2 spine malformation); neurologic abnormalities; intellectual disability; and brain anomalies (hydrocephalus, dilatation of the lateral ventricles, and Chiari 1 malformation). Cardiovascular anomalies may include mitral valve prolapse, mitral regurgitation/incompetence, aortic regurgitation, and aortic root dilatation. Minimal subcutaneous fat, abdominal wall defects, myopia, and cryptorchidism in males are also characteristic findings.
A synthetic, N-alkylated imino analogue of D-glucose. Miglustat competitively and reversibly binds to and inhibits the activity of UDP-glucose ceramide glucosyltransferase, which catalyzes the initial step in the synthesis of glycosphingolipids (GSL). This leads to a decrease in the production of glycosphingolipid, which has important roles in various cellular processes. Miglustat can be used in substrate reduction therapy in diseases in which the enzyme glucocerebrosidase, that is responsible for the breakdown of GSL, is deficient.
The dihydrochloride salt form of the active levorotatory enantiomer of cetirizine, levocetirizine; a third generation, non-sedating, selective histamine H1 receptor antagonist, with antihistamine, anti-inflammatory and potential anti-angiogenic activities. Levocetirizine competes with endogenous histamine for binding at peripheral H1-receptor sites on the effector cell surface. This prevents the negative symptoms associated with histamine release and an allergic reaction. In addition, as histamine plays an important role in angiogenesis during an allergic inflammatory reaction, blocking the action of histamine may modulate the expression of proangiogenic factors and thus may prevent angiogenesis. As a third-generation histamine H1 receptor antagonist, levocetirizine has fewer side effects than most second-generation antihistamines.
The calcium salt form of fosamprenavir, prodrug of amprenavir, and a human immunodeficiency virus (HIV) protease inhibitor with antiviral property. Fosamprenavir is converted to amprenavir by cellular phosphatases in the epithelial cells of the intestine. Then amprenavir binds to the active site of HIV-1 protease, thereby preventing the proteolytic cleavage of viral Gag-Pol polypeptide into individual functional proteins, thereby leading to the formation of immature non-infectious viral particles.
A benign, darkly pigmented skin lesion characterized by proliferation of keratinocytes and melanocytes.
The mesylate salt form of gatifloxacin, a synthetic 8-methoxyfluoroquinolone with antibacterial activity against a wide range of gram-negative and gram-positive microorganisms. Gatifloxacin exerts its effect through inhibition of DNA gyrase, an enzyme involved in DNA replication, transcription and repair, and inhibition of topoisomerase IV, an enzyme involved in partitioning of chromosomal DNA during bacterial cell division.
Failure of the smooth muscle fibers of the gastrointestinal tract to relax at any one point of junction of one part with another.
A small round cell tumor confined to a specific area of the thoracic cavity without evidence of spread to another anatomic site.
A non-invasive or invasive adenocarcinoma arising from the neoplastic glandular cells in an adenomatous polyp.
A morphologic variant of papillary carcinoma of the thyroid gland that more often affects young patients and commonly metastasizing to the lungs. It is characterized by a diffuse infiltration of the thyroid gland by malignant follicular cells, squamous metaplasia, stromal fibrosis, and lymphocytic infiltration.
An astrocytic tumor appearing before the age of twenty one without designation of benign or malignant nor designated location.
Retinoblastoma during childhood that has not spread beyond the eye.
Retinoblastoma during childhood that has spread beyond the eye.
A WHO grade I large cystic tumor that occurs almost exclusively in infants, with a prominent desmoplastic stroma having a neuroepithelial population of neoplastic astrocytes together with a variable neuronal component. It involves the superficial cerebral cortex and leptomeninges, and often attaches to the dura. Although clinically it presents as a large tumor, it generally has a good prognosis following surgical resection. (Adapted from WHO)
Congenital occlusion of the vagina or adhesion of the walls of the vagina causing occlusion.
Stage 0 includes: (Tis, N0, M0) and (Ta, N0, M0). Tis: Carcinoma in situ. Ta: Non-invasive verrucous carcinoma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
A finding indicating the presence of blood in stool. It is the result of gastrointestinal hemorrhage and it may be easily seen in stool or may be identified microscopically.
A malignant neoplasm that affects the sweat glands.
A combination product containing prochlorperazine maleate and isopropamide iodide that was used as an antiemetic agent.
Stage IV includes: (Any T, Any N, M1). M1: Distant metastasis (excludes metastasis within the peritoneal cavity). (AJCC 6th and 7th eds.)
A rare, slow-growing neuroepithelial neoplasm of uncertain origin affecting adults. It is located in the third ventricle. It is characterized by the presence of epithelioid cells which express GFAP, and mucinous stroma which contains lymphoplasmacytic infiltrates.
A diverse group of carcinomas of the thymus gland, previously known as thymoma type C. It includes morphologic variants derived from purely epithelial cells, as well as from cells with neuroendocrine differentiation.
A naturally-occurring form of vitamin E, a fat-soluble vitamin with potent antioxidant properties. Considered essential for the stabilization of biological membranes (especially those with high amounts of polyunsaturated fatty acids), d-alpha-Tocopherol is a potent peroxyl radical scavenger and inhibits noncompetitively cyclooxygenase activity in many tissues, resulting in a decrease in prostaglandin production. Vitamin E also inhibits angiogenesis and tumor dormancy through suppressing vascular endothelial growth factor (VEGF) gene transcription. (NCI04)
Reference to a chemical group or moiety that can complex or chelate a metal ion.
A process that involves the binding of any member of the tumor necrosis factor family to a cognate receptor. These interactions are involved in regulation of signaling cascades that mediate inflammation, immune cell functions and organogenesis.
A sub-family of smad proteins that inhibit cell signaling by RECEPTOR-REGULATED SMAD PROTEINS. They form autoinhibitory feedback loops in the TGF-BETA signaling pathway and mediate signaling cross-talk with other signaling pathways
A series of molecular signals initiated by the cross-linking of an antigen receptor on a B cell. [GOC:add]
A series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell. [GOC:add]
Any series of molecular signals generated as a consequence of a glucocorticoid binding to its receptor. [GOC:mah]
The chemical reactions and pathways involving L-phenylalanine, the L-enantiomer of 2-amino-3-phenylpropanoic acid, i.e. (2S)-2-amino-3-phenylpropanoic acid. [CHEBI:17295, GOC:go_curators, GOC:jsg, GOC:mah]
A process that begins with the synthesis of a pri-miRNA from a DNA template by RNA Polymerase II, which is then enzymatically processed to produce a pre-miRNA intermediate by the microprocessor complex, and ends with the release of the mature miRNA from the pre-miRNA catalyzed by the enzyme Dicer.
The production of PEPTIDES or PROTEINS by the constituents of a living organism. The biosynthesis of proteins on RIBOSOMES following an RNA template is termed translation (TRANSLATION, GENETIC). There are other, non-ribosomal peptide biosynthesis (PEPTIDE BIOSYNTHESIS, NUCLEIC ACID-INDEPENDENT) mechanisms carried out by PEPTIDE SYNTHASES and PEPTIDYLTRANSFERASES. Further modifications of peptide chains yield functional peptide and protein molecules.
The chemical reactions and pathways involving retinol, one of the three compounds that makes up vitamin A. [GOC:jl, http://www.indstate.edu/thcme/mwking/vitamins.html, PMID:1924551]
Non-enzymatic addition of carbamoyl (-CONH2) on protein or amino acid functional groups from isocyanic acid or CARBAMOYL-PHOSPHATE. Carbamylation may induce a structural change that results in a functional loss and serves as a biomarker for protein aging and disease pathophysiology.
A malignant epithelial neoplasm that arises from the rectosigmoid area and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas. About 50% of colorectal carcinomas occur in the rectosigmoid area.
A recombinant, chimeric protein derived from a melanoma antigenic epitope (MAGE-3) and recognized by specific cytotoxic T lymphocytes. MAGE-3, a human peptide epitope present in the cytosol of melanoma cells, may be expressed as the fusion protein D1/3-Mage-3; this fusion protein may boost antitumoral immune responses when used in a vaccine formulation. (NCI04)
A proprietary oil-in-water emulsion specifically designed for combining protein preparations used in vaccines. SB-AS02B adjuvant contains monophosphoryl lipid A and QS21, a saponin extracted from the South American tree Quillaja Saponaria Molina. This agent may be used for formulating cancer-specific vaccine preparations such as those containing MAGE-3 melanoma protein. (NCI04)
A vaccine comprised of autologous dendritic cells pulsed with a recombinant prostate specific membrane antigen. (NCI)
A cancer vaccine consisting of lymphocytes harvested from a patient with lung cancer and induced to become antigen-presenting cells (APCs) known as dendritic cells. The dendritic cells are transduced with the gene encoding an antigen specific to the patient's cancer and then returned to the patient. In the host, the altered cells stimulate the immune system to mount a primary T cell response against lung tumor cells expressing the target antigen. Dendritic cell-autologous lung tumor vaccines have been investigated for use in cancer immunotherapy. (NCI04)
An orally active synthetic enantiomer of flurbiprofen. Tarenflurbil activates c-Jun N terminal kinase, increases AP-1 binding to DNA, and downregulates cyclin D1 expression, resulting in arrest of tumor cells in the G1 phase of the cell cycle and apoptosis. This agent also affects the expression of nuclear factor kappa B, a rapid response transcription factor that stimulates the immune response to tumor cells. R-flurbiprofen does not inhibit the enzyme cyclo-oxygenase.
A tumor-associated antigen belonging to the family of immunogenic testicular proteins that are aberrantly expressed in human cancers in a lineage-nonspecific fashion. Reverse transcription-PCR analysis showed NY-ESO-1 mRNA expression in a variable proportion of a wide array of human cancers, including melanoma, breast cancer, bladder cancer, prostate cancer, and hepatocellular carcinoma; and restricted expression in normal tissues, with high-level mRNA expression found only in testis and ovary tissues. The gene for NY-ESO-1 maps to Xq28 and codes for an 18-kDa protein having no homology with any known protein. NY-ESO-1 elicits a strong, integrated humoral and cellular immune response in a high proportion of patients with NY-ESO-1-expressing tumors and is under investigation as a cancer immunotherapy agent.
An oral polymer matrix-based rinse formulation that contains N-acetylcysteine, an antioxidant amino acid derivative with antiinflammatory properties. RK-0202 may alleviate symptoms of radiation-induced oral mucositis. (NCI04)
An autologous vaccine composed of dendritic cells (DC) that have been transduced with a p53 tumor suppressor gene-modified virus. When the autologous dendritic cell-adenovirus p53 vaccine is administered, the host cytotoxic T lymphocytes (CTL) are directed against p53-positive tumor cells, which may result in tumor cell death and decreased tumor growth. (NCI04)
An attenuated, replication-competent, oncolytic strain of Newcastle disease virus. PV701 selectively lyses tumor cells. The selectivity of this agent is related to defects in the interferon-mediated antiviral response found in tumor cells. (NCI04)
A recombinant agent consisting of a genetically-modified adenovirus 5 vector encoding the protein cytokine tumor necrosis factor (TNF) alpha. TNF exhibits potent anti-tumor cytolytic properties; the adenovirus 5 vector efficiently infects tumor cells, delivering tumor-specific TNF.
A substance being studied in the treatment of certain types of cancer, including non-Hodgkin lymphoma, breast, colon, lung, ovarian, and prostate. Enzastaurin blocks certain cell signaling pathways, and may prevent the growth of new blood vessels that tumors need to grow. It is a type of serine threonine kinase inhibitor and a type of antiangiogenesis agent.
The hexyl ester of 5-aminolevulinic acid (ALA) with photodynamic properties. As a precursor of photoactive porphorins, hexyl 5-aminolevulinate induces the endogenous production of the photosensitizer protoporphyrin IX (PPIX) which accumulates selectively in tumor tissue. When exposed to specific wavelengths of light, PPIX is activated and, depending on the wavelength and/or intensity of light, either fluoresces, thereby allowing tumor imaging, or induces tumor cell apoptosis.
A recombinant chimeric protein composed of the heat shock protein 65 (Hsp65) from Mycobacterium bovis, and the human papilloma viral (HPV) protein E7. Hsp65, similar to other members of its family of proteins, elicits a strong immune response and may be used to design vaccines against a number of different cancers. E7 protein is involved in carcinogenesis of anal and cervical tumors, and represents a tumor antigen that may be specifically targeted by lymphocytes. (NCI04)
A radioimmunoconjugate of the humanized monoclonal antibody CC49 labeled with iodine I 131. Iodine I 131 monoclonal antibody CC49 delivers beta and gamma radiation-emitting I 131 radionuclide specifically to tumor cells that express tumor-associated glycoprotein (TAG)-72, allowing localization of TAG-72-expressing tumor cells with radioimaging devices in diagnostic applications or resulting in specific TAG-72-expressing tumor cell radiocytotoxicity in therapeutic applications. Monoclonal antibody CC49 binds to TAG-72, a pancarcinoma antigen, with high affinity.
A pentafluorophenylsulfonamide compound with potential antineoplastic activity. T900607 inhibits tubulin polymerization by binding irreversibly to colchicine binding sites, resulting in cell cycle arrest and apoptosis. (NCI04)
The eicosasodium salt of a mixed-backbone antisense oligodeoxynucleotide with chemosensitizing properties. Custirsen inhibits testosterone-repressed prostate message-2 (TRPM-2). Administration of custirsen abrogates the anti-apoptotic effect of TRPM-2, thereby sensitizing cells to chemotherapy and resulting in tumor cell death. TRPM-2 is an anti-apoptotic clusterin that is overexpressed by prostate cancer cells and is associated with chemoresistance.
A recombinant fowlpox virus vaccine with potential antineoplastic activity. Binding to the melanoma antigen tyrosinase, recombinant fowlpox-tyrosinase vaccine generates cellular immune responses against melanoma cells expressing the tyrosinase antigen; this effect is enhanced by the co-administration of interleukin 2 (IL-2). Fowlpox virus is an attractive vector because its genome is easy to manipulate and it is replication incompetent in mammalian cells.
A peptide derived from cytomegalovirus (CMV) internal matrix protein pp65. CMV pp65 peptide antigen is used in recombinant vaccinia virus as an HLA-A-restricted epitope to produce vaccines and specific CD8+ and CD4+ cell responses against CMV infection, a serious complication of allogeneic bone marrow transplantation (BMT). In BMT, CMV infection may be prevented by passive immunization with donor-derived CMV-pp65-specific T-cell clones if provided early post-BMT.
A cancer vaccine composed of tumor-specific idiotype determinants derived from an individual's tumor cells which are conjugated to keyhole limpet hemocyanin, an immunostimulant carrier protein. When injected into the individual from whom the tumor cells were isolated, this vaccine may stimulate an antitumoral cytotoxic T-lymphocytic immune response. (NCI04)
An orally bioavailable quinazoline with potential antineoplastic activity. CP-724,714 selectively binds to the intracellular domain of HER2, reversibly inhibiting its tyrosine kinase activity and resulting in suppression of tumor cell growth. HER2, a member of the epidermal growth factor receptor (EGFR) family, is overexpressed in many adenocarcinomas, particularly breast cancers. (NCI04)
Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder expressed in infancy and characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies (Muraoka et al., 1997). King et al. (2005) proposed a new classification of CAMT based on the course and outcome of the disease, as exemplified by 20 patients: CAMT type I (11 patients) was characterized by early onset of severe pancytopenia, decreased bone marrow activity, and very low platelet counts. CAMT type II (9 patients) was somewhat milder and characterized by transient increases of platelet counts up to nearly normal values during the first year of life and an onset of bone marrow failure at age 3 or later.
A rare severe phenotypic variant of dyskeratosis congenita with onset in early childhood. The syndrome has features of dyskeratosis congenita (for example skin hyper/hypopigmentation, nail dystrophy, high risk of bone marrow failure and cancer, developmental delay sparse and fine hair) in conjunction with bilateral exudative retinopathy and intracranial calcifications.
Syndrome is characterised by haematological anomalies (Fanconi anaemia, leukaemia and lymphoma) often appearing during childhood. Anomalies of the limbs and hands are also present: bifid or hypoplastic thumbs, cutaneous syndactyly and ulnar and radial defects. The syndrome has been described in several families. Transmission is autosomal dominant.
A very rare genetic malformation syndrome with characteristics of upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances and congenital bilateral non-progressive mixed hearing loss. Prevalence is not known. To date, four affected families from Venezuela, Italy, Hungary, and Turkey (discordant monozygotic twins) have been described. The syndrome has been linked to mutations in the SALL4 gene (20q13.2) encoding a transcription factor. Inherited in an autosomal dominant manner.
SAMD9L-related ataxia-pancytopenia (ATXPC) syndrome is characterized by cerebellar ataxia, variable hematologic cytopenias, and predisposition to marrow failure, myelodysplasia, and myeloid leukemia, sometimes associated with monosomy 7. The onset of hematologic abnormalities has been reported as early as age three months. The cytopenias in all cell lineages ranged from mild to very severe. Onset of neurologic impairment is variable. Nystagmus, dysmetria, increased deep tendon reflexes, and clonus are common. Gait impairment and other neurologic abnormalities are slowly progressive.
A chronic myelogenous leukemia occurring during childhood.
IDEC-152 was developed to decrease the body's response to allergens, thereby affecting diseases related to asthma and allergic disorders. This chimeric monoclonal antibody binds to the CD23 receptor, by which IDEC-152 may favorably influence asthma through its selective regulation of IgE production and its inhibition of other inflammatory pathways.
An immunoconjugate that consists of a humanized monoclonal antibody (MLN591), directed against prostate-specific membrane antigen linked to a maytansinoid (DM1). The monoclonal antibody moiety of MLN2704 binds to tumor cells expressing prostate-specific membrane antigen; MLN274 is then internalized into the tumor cell where the DM1 maytansinoid moiety binds to tubulin and inhibits tubulin polymerization and microtubule assembly, resulting in a disruption of microtubule activity and cell division, and cell death. (NCI04)
A proprietary cancer DNA vaccine that contains multiple natural and modified epitopes derived from the four tumor associated antigens, CEA, HER2/neu, p53, and MAGE 2/3. EP-2101 also includes CAP1-6D, a heteroclitic CEA analog, and PADRE, a proprietary universal T-cell epitope that serves to enhance the immunogenicity of the epitopes. This agent has been shown to elicit cytotoxic T-lymphocyte responses against tumor cells expressing these multiple epitopes. (NCI04)
A fully human monoclonal antibody with potential antineoplastic activity. MDX-060 is a fully humanized antibody that targets CD30, a member of the tumor necrosis factor receptor superfamily found on activated lymphocytes. CD30 is over-expressed in various lymphoproliferative disorders, Hodgkin disease and other lymphomas, and other cancers. (NCI04)
A therapeutic formulation consisting of camptothecin, an alkaloid isolated from the Chinese tree Camptotheca acuminata, conjugated with polyglutamate. During the S phase of the cell cycle, camptothecin selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. Conjugation with polyglutamate renders this agent more water soluble and less toxic than the parent molecule. (NCI04)
A cancer vaccine consisting of a recombinant fowlpox virus encoding human prostate-specific antigen (PSA) and TRICOM, a combination of three immunostimulants (i.e., B7.1, ICAM-1, and LFA-3). Administration of this agent may induce a cytotoxic T cell response against PSA-expressing tumor cells. Dendritic cells infected with TRICOM vectors greatly enhance naive T-cell activation and peptide-specific T-cell stimulation. Fowlpox virus is an attractive vector because its genome is easy to manipulate and it is replication incompetent in mammalian cells.
A vaccine consisting of a preparation of allogeneic lymphocytes that encode a gene for telomerase. In transgenic lymphocyte immunization, the transgenic cells are infused into the patient, where they serve as antigen- presenting cells (APCs) with the dual function of antigen synthesis and presentation. Vaccination produces an immune response targeting cancer cells expressing telomerase. (NCI04)
A humanized monoclonal antibody directed against MUC1, a mucin glycoprotein overexpressed in breast and other carcinomas. Monoclonal antibody HuHMFG1 stimulates antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells expressing MUC1, resulting in a decrease in tumor burden. (NCI04)
A humanized recombinant monoclonal antibody directed against the extracellular dimerization domain of the HER-2 tyrosine kinase receptor. Binding of the antibody to the dimerization domain of the HER-2 tyrosine kinase receptor protein directly inhibits the ability of the HER-2 tyrosine kinase receptor protein (the most common pairing partner) to dimerize with other HER tyrosine kinase receptor proteins; inhibiting receptor protein dimerization prevents the activation of HER signaling pathways, resulting in tumor cell apoptosis. (NCI04)
An epithelial neoplasm arising from the thymus. It may be associated with myasthenia gravis, pure red cell aplasia, and hypogammaglobulinemia. It includes thymoma type B1 which is a thymoma of low grade malignant potential, thymoma type B2 which is a thymoma of moderate malignancy, and thymoma type B3 which is also known as well differentiated thymic carcinoma.
A preparation of cytotoxic T-lymphocytes (CTL), specifically reactive to Epstein-Barr virus (EBV) latent membrane protein-2A (LMP2A), with potential antineoplastic activity. T-lymphocytes are exposed ex vivo to dendritic cells (DCs) transfected with a replication-deficient adenovirus encoding EBV LMP2A. Subsequently, LMP2A-specific CTLs are exposed to EBV infected cells transfected with adenovirus encoding LMP2A, thereby further stimulating CTLs. Administered to patients with EBV-positive tumors, LMP2A-specific CTLs target LMP2A-positive cells, resulting in cell lysis and inhibition of cancer cell proliferation. EBV LMP2A may be expressed in various malignancies, including nasopharyngeal carcinoma and Hodgkin and non-Hodgkin lymphomas.
A recombinant cancer vaccine made with tumor-derived heat shock protein 70 (HSP70) peptide complexes. HSP70 associates with antigenic peptides, transporting them into antigen presenting cells (APC) for processing. Tumor-derived HSP70-peptide complexes used in vaccine preparations have been shown to prime tumor immunity and tumor-specific T cells in animal models. (NCI04)
This entity includes cases that have clinical, laboratory, and morphologic features that support the diagnosis of both a myelodysplastic syndrome and a myeloproliferative neoplasm, but do not meet the criteria for any of the other entities included in the myelodysplastic/myeloproliferative neoplasm category. (WHO, 2001)
A pegylated form of recombinant human erythropoietin, a glycosylated protein naturally produced in the kidney that stimulates erythrocyte production in the bone marrow. Methoxypolyethylene glycol epoetin beta may reverse anemias induced by cancer therapy. (NCI04)
A vaccine containing a recombinant vaccinia virus that encodes the gene for human mucin-1, a tumor-associated antigen. Upon administration, recombinant vaccinia-MUC-1 vaccine may elicit a MUC-1-specific cytotoxic T cell response against tumor cells bearing MUC-1.
A radioimmunotherapeutic agent consisting of a humanized murine monoclonal antibody (hu3S193) directed against the tumor-associated Lewis Y epithelial antigen chelated to the radioisotope yttrium-90. Yttrium Y 90 monoclonal antibody Hu3S193 binds to Lewis Y epithelial antigen-expressing tumor cells, selectively delivering a cytotoxic dose of beta radiation. (NCI04)
A peptide cancer vaccine consisting of a combination of peptides derived form several melanoma epitopes. Vaccination with multi-epitope melanoma peptide vaccine stimulates the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the corresponding antigens, resulting in tumor cell lysis. This vaccine may stimulate a broader CTL response compared to single-antigen vaccines. (NCI04)
A multivalent vaccine consisting of peptides derived from melanoma-associated antigens and an adjuvant peptide derived from tetanus toxoid. Vaccination with this agent may stimulate a host cytotoxic T-cell response against tumor cells expressing melanoma-associated antigens, resulting in tumor cell lysis. (NCI04)
A benzopyran with potential antineoplastic activity. CC-8490 acts as a selective estrogen receptor modulator (SERM), inhibiting the proliferation of estrogen-sensitive breast cancer cells. This agent also inhibits growth and induces apoptosis of glioblastoma cells via a mechanism independent of estrogen receptor-related mechanisms. (NCI04)
An autologous lung cancer vaccine consisting of patient-specific lung cancer cells genetically modified to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), an immunostimulatory cytokine. GM-CSF modulates the proliferation and differentiation of a variety of hematopoietic progenitor cells with some specificity towards stimulation of leukocyte production and may reverse treatment-induced neutropenias. This agent also promotes antigen presentation, up-regulates antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function and may augment host antitumoral immunity. For safety, cells are irradiated prior to vaccination. (NCI04)
A recombinant, chimeric toxin composed of human transforming growth factor alpha (TGF-alpha) fused to a fragment of Pseudomonas exotoxin (PE38) without its cell-binding domain. The TGF-alpha moiety of the agent attaches to tumor cells expressing the epithelial growth factor receptor (EGFR); the exotoxin induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis. (NCI04)
A vaccine composed of tumor cells isolated from the tumor of one patient, killed and processed, and administered to another patient to stimulate cytotoxic immune responses to a similar tumor cell type. The cells found in this type of whole-cell vaccine express many cell-surface tumor-associated antigens. This vaccine is frequently administered with an adjuvant immunostimulant. (NCI04)
A humanized monoclonal antibody with antineoplastic activity. Matuzumab binds the epidermal growth factor receptor (EGFR) with high affinity, competitively blocking natural ligand binding and inhibiting receptor-mediated downstream signalling, resulting in impaired tumor cell proliferation.
A liposome-encapsulated formulation of the benzoquinazoline folate analog OSI-7904 with antineoplastic activity. As a thymidylate synthase inhibitor, OSI-7904 noncompetitively binds to thymidylate synthase, resulting in inhibition of thymine nucleotide synthesis and DNA replication. Liposome encapsulation improves the efficacy and increases the half-life of OSI-7904. (NCI04)
An orally bioavailable tyrosine kinase inhibitor. AG-013736 inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGF), thereby exerting an anti-angiogenic effect. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=352181&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=352181&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C38718"" NCI Thesaurus)
A replication-defective adenovirus containing a gene that encodes the human protein L523S with potential antineoplastic activity. Upon administration, recombinant adenovirus-L523S vaccine expresses L523S, which may stimulate antibody and cytotoxic T lymphocyte (CTL) responses against tumor cells expressing L523S. L523S is an RNA-binding protein that belongs to the KOC (K homology domain containing protein over-expressed in cancer) family of proteins. As an oncofetal protein, L523S is normally expressed in early embryonic tissues and certain normal adult tissues such as colon, fallopian tube, gall bladder, and ovary tissues but may be overexpressed in squamous cell cancers of the lung.
An oral high dose formulation of calcitriol, the biologically active form of Vitamin D. Acting as a ligand for the Vitamin D receptor (VDR), DN-101 binds to the VDR inhibiting VDR-regulated gene transcription involved in cell proliferation, differentiation and apoptosis. (NCI)
A radio-sensitizing pyrimidine nucleoside with potential antineoplastic activity. Cytochlor is metabolized first to a phosphate derivative, CldCMP, by the enzyme deoxycytidine kinase and then to the active uracyl derivative, CldUMP, by the enzyme dCMP deaminase; deoxycytidine kinase and dCMP deaminase have been found in abnormally high concentrations in most cancers. CldUMP, the active metabolite, incorporates into DNA and, upon exposure to radiation, induces the formation of uracil radicals and double-strand DNA breaks. (NCI04)
A phosphorothioate oligonucleotide harboring nucleotide sequences complementary to tumor suppressor p53 mRNA. EL625 hybridizes with p53 mRNA molecules, and induces Rnase H dependent hydrolysis of p53 transcripts in the double stranded section of the hybrids, thereby resulting in loss of p53 production. Loss of p53 activity leads to sensitization of cancer cells to other therapeutics. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=354249&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=354249&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C37454"" NCI Thesaurus)
An agent consisting of the arginine-degrading enzyme arginine deiminase combined with polyethylene glycol (20,000 MW) (ADI-PEG 20) with potential antineoplastic activity. Upon administration, arginine deiminase breaks down the amino acid arginine into citrulline. Although arginine is a nonessential amino acid for normal human cells, certain cancer cells are autotrophic for arginine and need arginine in order to survive. Depletion of arginine may lead to an inhibition of cellular proliferation in those cancer cells. ADI is coupled to PEG in order to enhance this agent's half-life.
An orally available selective antagonist of the endothelin-A (ET-A) receptor with potential antineoplastic activity. ZD4054 binds selectively to the ET-A receptor, thereby inhibiting endothelin-mediated mechanisms that promote tumor cell proliferation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=355727&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=355727&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48430"" NCI Thesaurus)
A murine IgG1 anti-CD45 monoclonal antibody (MoAb) with immunotherapeutic activity. CD45 antigen, a receptor protein-tyrosine phosphatase essential for T cell development and lymphocyte activation, is expressed on virtually all leukocytes. MoAb BC8 has specificity for hematopoietic tissues and may be used in targeted immunotherapy.
An orally bioavailable antiangiogenic isocoumarin with potential antineoplastic activity. NM-3 inhibits vascular endothelial growth factor (VEGF), a pro-angiogenic growth factor, thereby inhibiting endothelial cell proliferation. This agent also induces apoptosis by a mechanism involving reactive oxygen species. (NCI04)
The liposomal formulation of SN-38 (7-ethyl-10-hydroxy-camptothecin), a biologically active metabolite of the prodrug irinotecan, with potential antineoplastic activity. SN-38 binds to and inhibits topoisomerase I by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication, and apoptosis. SN-38 has been reported to exhibit up to 1,000-fold more cytotoxic activity against various cancer cells in vitro than irinotecan. The liposomal formulation of SN-38 increases the solubility of SN-38, which is a relatively insoluble compound, and improves the pharmacodynamic profile as compared to SN-38 alone.
An orally bioavailable form of the element gallium (Ga) composed of a trivalent gallium cation (Ga3+) coordinated to three maltolate ligands, with anti-inflammatory, anti-proliferative, antineoplastic, analgesic, antiresorptive and antibacterial activities. Upon administration of gallium maltolate, Ga3+, which is structurally similar to the ferric ion (Fe3+), competes with and replaces Fe3+ in many vital Fe 3+-mediated biological reactions.. Unlike Fe3+, Ga3+ cannot be reduced, cannot participate in redox reactions and cannot mimic Fe3+ functions. In rapidly proliferating cells, such as cancer cells, high amounts of iron are needed for DNA synthesis. The incorporation of Ga3+ inactivates the Fe3+-dependent enzyme ribonucleotide reductase (RR), an enzyme essential for DNA synthesis, leading to an inhibition of DNA synthesis and induction of cell death in rapidly proliferating cells. Gallium similarly reduces bacterial cell growth. In addition, Ga3+ is able to suppress inflammation through the down-regulation of pro-inflammatory cells and the inhibition of pro-inflammatory cytokine secretion. Gallium also exerts analgesic effects due to the inhibition of Fe3+-dependent enzymes involved in inflammation and may interfere with the activity of certain metalloproteinases and neuropeptides that are implicated in pain. Also, gallium is able to inhibit bone resorption by osteoclasts, may inhibit metastasis to bone and may prevent the destruction of bone by tumors.
A genetically-engineered, chimeric mouse-human, anti-CD30 monoclonal antibody with potential antineoplastic activity. Monoclonal antibody SGN-30 specifically binds to the receptor CD-30, a member of the tumor necrosis factor receptor super-family, which may be overexpressed on the surfaces of Hodgkins lymphoma cells and anaplastic-large cell lymphoma cells. After binding to CD30, this agent interferes with the G1 phase of the cell cycle, thereby inducing growth arrest and apoptosis in susceptible tumor cell populations. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=357600&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=357600&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2007"" NCI Thesaurus)
An engineered monoclonal antibody (MAb) directed against the tumor-associated antigen (TAA) human epithelial cell adhesion molecule (Ep-CAM; EpCAM; CD326), with potential antitumor activity. Upon administration, anti-Ep-CAM monoclonal antibody ING-1 binds to Ep-CAM, which may result in a cytotoxic T-lymphocyte (CTL)-mediated immune response against Ep-CAM-expressing tumor cells. Ep-CAM, a cell surface protein upregulated on many tumor cell types, promotes the proliferation, migration and invasiveness of tumor cells.
A disease characterized by the chronic, progressive spread of lesions from New World cutaneous leishmaniasis caused by species of the L. braziliensis complex to the nasal, pharyngeal, and buccal mucosa some time after the appearance of the initial cutaneous lesion. Nasal obstruction and epistaxis are frequent presenting symptoms.
A liver disorder caused by primary or secondary defects in the function of the mitochondria in the hepatocytes.
Laryngo-onycho-cutaneous (LOC) syndrome is a disorder that leads to abnormalities of the voicebox (laryngo-), finger- and toenails (onycho-), and skin (cutaneous). Many of the condition's signs and symptoms are related to the abnormal growth of granulation tissue in different parts of the body. This red, bumpy tissue is normally produced during wound healing and is usually replaced by skin cells as healing continues. However, in people with LOC syndrome, this tissue grows even when there is no major injury.One of the first symptoms in infants with LOC syndrome is a hoarse cry due to ulcers or overgrowth of granulation tissue in the voicebox (the larynx). Excess granulation tissue can also block the airways, leading to life-threatening breathing problems; as a result many affected individuals do not survive past childhood.In LOC syndrome, granulation tissue also grows in the eyes, specifically the conjunctiva, which are the moist tissues that line the eyelids and the white part of the eyes. Affected individuals often have impairment or complete loss of vision due to the tissue overgrowth.Another common feature of LOC syndrome is missing patches of skin (cutaneous erosions). The erosions heal slowly and may become infected. People with LOC syndrome can also have malformed nails and small, abnormal teeth. The hard, white material that forms the protective outer layer of each tooth (enamel) is thin, which contributes to frequent cavities.LOC syndrome is typically considered a subtype of another skin condition called junctional epidermolysis bullosa, which is characterized by fragile skin that blisters easily. While individuals with junctional epidermolysis bullosa can have some of the features of LOC syndrome, they do not usually have overgrowth of granulation tissue in the conjunctiva.
A benign, well circumscribed neoplasm that arises from the breast. Representative examples include apocrine adenoma, tubular adenoma, and pleomorphic adenoma.
The presence of developmental dysplasia of the acetabular part of hip bone.
Rare and often fatal drug complication which affects patients undergoing long-term treatment with high doses of PROPOFOL. It is characterized by METABOLIC ACIDOSIS; HYPERLIPIDEMIA; RHABDOMYOLYSIS; cardiovascular CIRCULATORY COLLAPSE; CARDIAC FAILURE; and KIDNEY FAILURE.
Abnormality of an amino acid metabolic process.
A disorder characterized by an uncomfortable persistent sensation in the area of the laryngopharynx.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the pancreas. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
Bleeding originating from the bile duct.
Prostate carcinoma that grows and continues to spread despite the surgical removal of the testes or medical intervention to block androgen production.
An invasive adenocarcinoma of the breast with a favorable prognosis. It is composed of tubular structures lined by a single layer of epithelium.
A state of consciousness that permits the formation of explicit and implicit memories while under general anesthesia.
A reduction in the circulating levels of all the major classes of immunoglobulin. is characterized by profound decreases in all classes of immunoglobulin with an absence of circulating B lymphocytes.
An inflammatory process affecting the mucous membrane of the rectum.
Impaired ability to recognize letters or numbers drawn by an examiner's fingertip on the patient's skin (the patients eyes are closed or covered throughout this examination).
A radioconjugate consisting of the octreotide derivative edotreotide labeled with yttrium 90 (Y-90) with potential radiotherapeutic uses. Similar to octreotide, yttrium Y 90-edotreotide binds to somatostatin receptors (SSTRs), especially type 2 receptors, present on the cell membranes of many types of neuroendocrine tumor cells, delivering tissue-specific, beta-emitting nuclide Y-90-mediated cytotoxicity to SSTR-positive cells. Yttrium Y 90-edotreotide is produced by substituting tyrosine for phenylalanine at the 3 position of the somatostatin analogue octreotide and chelating the substituted octreotide to Y-90 via dodecanetetraacetic acid (DOTA).
A synthetic indolocarbazole with antineoplastic activity. Edotecarin inhibits the enzyme topoisomerase I through stabilization of the DNA-enzyme complex and enhanced single-strand DNA cleavage, resulting in inhibition of DNA replication and decreased tumor cell proliferation. (NCI04)
A class of vaccines that consist of anti-idiotype monoclonal antibodies against the tumor-associated antigen disialoganglioside GD2 with potential antineoplastic activity. Vaccination with a monoclonal antibody GD2 anti-idiotype vaccine produces an immunoglobulin response against GD2 with subsequent destruction of GD2 positive tumor cells via antibody-dependent cellular cytotoxicity (ADCC). GD2 is overexpressed in melanoma, neuroblastoma, soft tissue sarcoma, and small cell carcinoma of the lung. (NCI04)
A synthetic photosensitizer agent containing a large macrocyclic ring chelated with silicon. Silicon phthalocyanine 4 localizes primarily in mitochondrial cytosolic membranes and, after photoexcitation, forms reactive oxygen species that induce apoptosis.
A recombinant chimeric protein composed of the heat shock protein 65 (Hsp65) from Mycobacterium bovis, and the human papilloma viral (HPV) protein E7. Hsp65, similar to other members of its family of proteins, elicits a strong immune response and may be used to design vaccines against a number of different cancers. E7 protein is involved in carcinogenesis of anal and cervical tumors, and represents a tumor antigen that may be specifically targeted by lymphocytes. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=269165&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=269165&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2811"" NCI Thesaurus)
A mixed-backbone antisense oligodeoxynucleotide with chemosensitizing properties. OGX-011 inhibits testosterone-repressed prostate message-2 (TRPM-2). Administration of OGX-011 abrogates the anti-apoptotic effect of TRPM-2, thereby sensitizing cells to chemotherapy and resulting in tumor cell death. TRPM-2 is an anti-apoptotic clusterin that is overexpressed by prostate cancer cells and is associated with chemoresistance. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=271195&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=271195&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1055"" NCI Thesaurus)
A dolastatin-10 derivative. Soblidotin inhibits tubulin polymerization, resulting in cell cycle arrest and induction of apoptosis. (NCI04)
A pegylated form of recombinant human erythropoietin, a glycosylated protein naturally produced in the kidney that stimulates erythrocyte production in the bone marrow. Methoxypolyethylene glycol epoetin beta may reverse anemias induced by cancer therapy. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=339378&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=339378&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C38687"" NCI Thesaurus)
A humanized monoclonal immunoglobulin G1 antibody with potential antineoplastic activity. Siplizumab binds to CD2, a specific receptor found in T cells and NK cells, thereby triggering a host immune response that results in lysis of CD2+ cells, selective suppression of the immune system, and control of activated T cell growth.
An extract prepared from the fruit of Morinda citrifolia, a plant that yields various herbal preparations. Morinda citrifolia fruit juice has antioxidant properties and may prevent tumorigenesis via inhibition of DNA-carcinogen adduct formation.
A pattern of valid appraisal of stressors with cognitive and/or behavioral efforts to manage demands related to well-being, which can be strengthened.
A pattern of cognitive information related to a specific topic, or its acquisition, which can be strengthened.
Change in or modification of the oxygenation of tissues
Autoimmune lymphoproliferative syndrome (ALPS), caused by defective lymphocyte homeostasis, is characterized by the following: Non-malignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly with or without hypersplenism) that often improves with age. Autoimmune disease, mostly directed toward blood cells. Lifelong increased risk for both Hodgkin and non-Hodgkin lymphoma. In ALPS-FAS (the most common and best-characterized type of ALPS, associated with heterozygous germline pathogenic variants in FAS), non-malignant lymphoproliferation typically manifests in the first years of life, inexplicably waxes and wanes, and then often decreases without treatment in the second decade of life; in many affected individuals, however, neither splenomegaly nor the overall expansion of lymphocyte subsets in peripheral blood decreases. Although autoimmunity is often not present at the time of diagnosis or at the time of the most extensive lymphoproliferation, autoantibodies can be detected before autoimmune disease manifests clinically. In ALPS-FAS caused by homozygous or compound heterozygous (biallelic) pathogenic variants in FAS, severe lymphoproliferation occurs before, at, or shortly after birth, and usually results in death at an early age. ALPS-sFAS, resulting from somatic FAS pathogenic variants in selected cell populations, notably the alpha/beta double-negative T cells (a/ß-DNT cells), appears to be similar to ALPS-FAS resulting from heterozygous germline pathogenic variants in FAS, although lower incidence of splenectomy and lower lymphocyte counts have been reported in ALPS-sFAS and no cases of lymphoma have yet been published.
Presence of an unusually high number of lentigines (singular: lentigo), which are flat, tan to brown oval spots.
Used to denote the transcription of DNA into RNA. The biochemical machinery includes sequence-specific DNA binding proteins that directly act in the regulation of the transcription process, other protein factors that participate in the assembly of the transcription complex, and RNA polymerase.
Preparations used as alternatives or supplements to hand washing with soap and water to destroy microorganisms and prevent transmission of pathogens. The active ingredient may be ETHANOL; 1-PROPANOL; or POVIDONE-IODINE in a gel, foam, or liquid solution.
The acetate salt form of estradiol, the most potent, naturally produced estrogen. Estradiol acetate diffuses through the cell membrane and binds to and subsequently activates the nuclear estrogen receptor found in the reproductive tract, breast, pituitary, hypothalamus, liver, and bone. The activated complex binds to the estrogen response element on the DNA and activates the transcription of genes involved in the functioning of the female reproductive system and secondary sex characteristics.
An adenoma that arises from the extrahepatic bile ducts. It is classified as papillary, tubular, or tubulopapillary.
A rare adenoma that arises from the intrahepatic biliary tree.
The developmental arrest and architectural distortion of the thymus that results in immunodeficiency.
A sustained temperature of 38C (100.4F) or greater beyond the first 24 hours following birth, or a temperature of 39C (102.2F) within the first 24 hours following birth. (adapted from ACOG)
A carcinoma arising from the anus and occurring in HIV-positive patients. Homosexual HIV-positive men have an increased risk of developing anal squamous cell carcinoma in comparison to the general male population. Sexually transmitted human papillomavirus is detected in the majority of the cases.
A carcinoma that arises from the cervix in a patient with acquired immunodeficiency syndrome.
Enterocolitis associated with the AIDS virus.
An opportunistic infection caused by herpes zoster in a patient with AIDS.
A malignant neoplasm arising from the anus and occurring in HIV-positive patients. Representative examples include squamous cell carcinoma and non-Hodgkin lymphoma. Homosexual HIV-positive men have an increased risk of developing such malignancies in comparison to the general male population.
A malignant neoplasm that arises from the cervix in a patient with acquired immunodeficiency syndrome. This category includes cervical carcinoma, Kaposi sarcoma, and non-Hodgkin lymphoma.
A non-Hodgkin lymphoma that develops in a patient with AIDS.
A non-Hodgkin lymphoma that arises from the cervix in a patient with acquired immunodeficiency syndrome.
Pelvic inflammatory disease that develops in a patient with HIV/AIDS.
A serious AIDS-related opportunistic infection of the lungs, caused by Pneumocystis jirovecii. It is one of the most common AIDS-related illnesses and is a major cause of morbidity in patients with AIDS. Signs and symptoms include cough, fever, dyspnea, and pain or tightness in the chest.
Primary effusion lymphoma occurring in HIV-positive patients.
AIDS related research with a minimum of 20% (or $100,000) relevance to individuals with hemophilia, a sex-linked hereditary blood defect that occurs almost exclusively in males and is characterized by delayed clotting of the blood and consequent difficulty in controlling hemorrhage even after minor injuries. (FMB)
A T-cell peripheral lymphoma morphologically indistinguishable from anaplastic large cell lymphoma, ALK-positive. It is characterized by the absence of the translocation involving the ALK gene and lacks expression of ALK fusion protein.
A T-cell peripheral lymphoma composed of usually large, pleomorphic, CD30 positive T-lymphocytes with abundant cytoplasm characterized by the presence of a translocation involving the ALK gene and expression of ALK fusion protein. Most patients present with peripheral and/or abdominal lymphadenopathy, and often have advanced disease and extranodal involvement.
A laboratory test result that indicates the presence of abnormal blood chemistry and/or hematology values.
A laboratory test result that indicates the presence of abnormal peripheral blood and/or bone marrow values.
A syndrome which occurs following withdrawal of an abused substance. Clinical signs vary depending on the substance that was abused and may include irritability, trembling and vomiting. The clinical course depends on the ability to manage the withdrawal symptoms.
A rare genetic syndrome featuring connective tissue abnormalities. Clinical signs include brachycephaly, arachnodactyly, receding mandible and joint laxity at the hands and feet.
A morphologic variant of lung adenocarcinoma characterized by the presence of acinar structures composed of columnar or cuboidal cells. (NCI05)
An invasive adenocarcinoma of the prostate gland composed of secretory cells. It is the most common histologic type of prostate adenocarcinoma. Several morphologic variants exist, including atrophic, pseudohyperplastic, foamy gland, and oncocytic variants.
A disorder which affects sensation in the hands. Clinical signs usually include tingling or numbness with onset in middle-age. There is a female predominance among those affected.
The most common variant of adult T-cell leukemia/lymphoma. It is characterized by systemic disease with a leukemic phase, generalized lymphadenopathy, and skin lesions. Hypercalcemia is commonly seen. -- 2004
Acute erythroid leukemia that is responding to therapy, i.e. It is not progressing and possibly regressing
Acute encephalitis that is characterized by bleeding.
An acute myeloid leukemia developing in patients with a prior history of myelodysplastic syndrome.
Acute myeloid leukemia characterized by the presence of abnormal bone marrow eosinophils and the characteristic cytogenetic abnormality t(16;16)(p13.1;q22) which results in the expression of the fusion protein CBFB-MYH11.
Acute myelomonocytic leukemia characterized by the presence of abnormal bone marrow eosinophils. It is associated with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22). It has a favorable prognosis.
The sudden shrinking and/or complete disappearance of the thymus gland; this often happens as a response to a physiologic stressor, such as infection or malnutrition.
A lung carcinoma characterized by a combination of small cell carcinoma and adenocarcinoma.
An adenocarcinoma that arises from and straddles the junction of the stomach and esophagus. The category of adenocarcinomas of the gastroesophageal junction also includes the majority of adenocarcinomas previously called gastric cardia adenocarcinomas. Squamous cell carcinomas that affect or cross the junction of the stomach and esophagus are classified as carcinomas of the distal esophagus. Adenocarcinoma of the gastroesophageal junction occurs more often in Caucasian middle aged and elderly males. Clinical signs and symptoms include dysphagia, abdominal pain, and weight loss. The prognosis depends on the completeness of the surgical resection, the number of lymph nodes involved by cancer, and the presence or absence of postoperative complications. The presence of TP53 mutations indicates worse prognosis.
An adenoid cystic carcinoma primarily involving the breast. Three morphologic patterns are seen: cribriform, trabecular, and solid. The prognosis is excellent.
An intramucosal malignant glandular epithelial infiltrate in a colonic adenoma. There is no evidence of submucosal invasion.
A rare carcinoma that arises from the thymus and is characterized by the presence of glandular and squamous carcinomatous components.
A disorder which limits movement of the eye following ocular surgery. It is caused by the inadvertent scarring down of the middle portion of the inferior oblique muscle at or near the insertion of the inferior rectus muscle. Clinical signs include hypotropia and excyclotropia. Surgical release of the incarcerated segment will usually correct the deviation of the affected eye.
A ganglioneuroblastoma arising from the adrenal gland.
An acute monoblastic and monocytic leukemia occurring in adults.
An astrocytic tumor occurring during adulthood. Representative examples include diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma.
An atypical meningioma that occurs during adulthood.
A morphologic variant of embryonal rhabdomyosarcoma occurring in adults. The neoplasm arises from organs containing a mucosal epithelial surface. It is characterized by the formation of a cambium layer in the affected tissue and polypoid nodules with an abundant myxoid stroma.
An ependymoma of the brain occurring in adults.
A brain glioblastoma that occurs during adulthood.
A medulloblastoma arising from the brain, occurring in adults.
A brain meningioma that occurs during adulthood.
A central nervous system embryonal tumor, not otherwise specified that occurs in adults.
A clear cell sarcoma of soft parts occurring during adulthood.
A desmoplastic small round cell tumor occurring in adults.
A low grade (WHO grade II) astrocytoma occurring during adulthood. It is characterized by a high degree of cellular differentiation, slow growth, and diffuse infiltration of neighboring brain structures.
A melanoma that arises from leptomeningeal melanocytes and occurs in adulthood.
A mesenchymal chondrosarcoma occurring in adults.
A myxoid chondrosarcoma occurring in adults.
A nodular lymphocyte predominant Hodgkin lymphoma occurring in adults.
An aggressive rhabdomyosarcoma occurring in adults. The neoplasm is characterized by the presence of bizarre round, spindle, and polygonal cells. Clinical presentation includes a rapidly enlarging painful mass usually in the lower extremities.
An ependymoma of the spinal cord occurring in adults.
A granulosa cell tumor that affects middle aged or postmenopausal women. Patients may present with uterine bleeding.
Wilms tumor of the kidney which occurs in adults.
A hepatocellular carcinoma that develops following exposure to aflatoxin.
A non-Hodgkin lymphoma with an aggressive clinical course. Representative examples include Burkitt lymphoma, mantle cell lymphoma, and angioimmunoblastic T-cell lymphoma.
An esophageal carcinoma that results from alcohol consumption. The alcohol-related esophageal carcinomas are always of squamous cell type. There is no association between alcohol consumption and esophageal adenocarcinomas.
A hepatocellular carcinoma that develops following alcohol-induced injury of the liver parenchyma.
A carcinoma that arises from the larynx and is caused by alcohol abuse.
Acute myeloid leukemia occurring as late complication of prior therapy with alkylating agents.
Acute myeloid leukemias and myelodysplastic syndromes arising as a result of the mutagenic effect of alkylating agents that are used for the treatment of malignant tumors. Patients usually develop a myelodysplastic syndrome which may evolve to a higher grade myelodysplastic syndrome or acute myeloid leukemia. A minority of patients present with an acute myeloid leukemia. Clonal cytogenetic abnormalities are frequently present and usually are unbalanced translocations or deletions of chromosomes 5 and 7. Patients with acute myeloid leukemia usually do not respond to treatment and have an unfavorable clinical outcome.
A disorder seen following cancer chemotherapy. It is the most common cause of therapy-related myelodysplastic syndromes. It typically manifests several years after initiation of single or multi-agent chemotherapy with alkylators. Mutagenic potential of alkylating agents is believed to be age and cumulative dose-dependent. Deletions in chromosomes 5 and 7 are associated with susceptibility to this disorder. Clinical signs may include fatigue, dyspnea, bruising and frequent infections. Clinical course may progress to bone marrow failure or acute myeloid leukemia that is refractory to treatment. Prognosis is dismal with survivability usually less than one year.
A change to taste and/or olfactory perception resulting from disease processes or treatment.
A very rare ameloblastic carcinoma that originates from a pre-existing benign ameloblastoma.
A rare, aggressive malignant tumor that originates from an odontogenic cyst in the maxillomandibular region. It combines the histologic features of an ameloblastoma and carcinoma.
An invasive carcinoma with glandular differentiation arising from the ampulla of Vater. Signs and symptoms include jaundice, abdominal pain, anorexia, nausea, vomiting, and weight loss.
An adenoma that arises from the ampulla of Vater and resembles the adenomas of the small and large intestines. Morphologically, according to the growth pattern, it may be classified as tubular, tubulovillous, or villous. Dysplasia is always present. Jaundice may be an early symptom.
A carcinoma with glandular and squamous differentiation arising from the ampulla of Vater. Signs and symptoms include jaundice, abdominal pain, anorexia, nausea, vomiting, and weight loss.
A carcinoma with glandular differentiation arising from the ampulla of Vater. Morphologically, it is characterized by the presence of glycogen-rich cells with hyperchromatic nuclei.
An invasive adenocarcinoma arising from the ampulla of Vater. Morphologically, it is characterized by the presence of intestinal-type malignant epithelial cells.
A carcinoma with glandular differentiation arising from the ampulla of Vater. Morphologically, it is characterized by the presence of mucoid stroma formation.
An adenocarcinoma arising from the ampulla of Vater. Morphologically, it is characterized by the presence of mucin-containing signet-ring cells.
An aggressive neuroendocrine carcinoma arising from the ampulla of Vater and the periampullary region. Morphologically, it is characterized by the presence of small malignant cells, necrosis, and a high mitotic rate. Signs and symptoms include jaundice, abdominal pain, anorexia, nausea, vomiting, and weight loss.
An intestinal-type adenoma arising from the ampulla of Vater. It is characterized by the presence of tubular epithelial structures and it is associated with dysplasia.
An intestinal-type adenoma arising from the ampulla of Vater. It is characterized by the presence of tubular and villous epithelial structures and it is associated with dysplasia.
An aggressive carcinoma arising from the ampulla of Vater. Morphologically, it is characterized by the presence of malignant epithelial cells without evidence of glandular or squamous differentiation. Signs and symptoms include jaundice, abdominal pain, anorexia, nausea, vomiting, and weight loss.
An intestinal-type adenoma arising from the ampulla of Vater. It is characterized by the presence of villous epithelial structures and it is associated with dysplasia.
An adenocarcinoma arising in the anal canal epithelium, including the mucosal surface, the anal glands, and the lining of fistulous tracts. The prognosis is related to the stage at diagnosis.
An anal adenocarcinoma arising from the lining of an anorectal fistulous tract. The overlying anal mucosa does not show evidence of neoplastic changes. Some cases are associated with Crohn disease.
A very rare tumor of the intestine, originating from the epithelium of the anal canal (including the mucosal surface, anal glands, and lining of fistulous tracts), macroscopically appearing as a nodular, often ulcerated, invasive mass located in the anal canal. Patients often present with rectal bleeding, as well as difficulty and pain during defecation. Inguinal lymphadenopathy, if present, usually indicates metastatic spread.
A precancerous neoplastic intraepithelial process involving the anal canal. When it is clinically noticeable, it may appear as an eczematous or papillary lesion, plaques, or papules. Morphologically, it is characterized by loss of epithelial stratification and nuclear polarity, cytologic atypia, and the presence of mitotic figures. It may be classified as low or high grade.
Paget disease involving the squamous epithelium of the anal canal.
A squamous cell carcinoma arising from the mucosa of the anal canal.
An anal adenocarcinoma arising from the lining of an anorectal fistulous tract or the anal glands. The overlying anal mucosa does not show evidence of neoplastic changes. It usually presents as a submucosal tumor.
A Kaposi sarcoma arising from the anus. HIV-positive patients have an increased risk of developing Kaposi sarcoma in the perianal region.
A well-circumscribed benign smooth muscle neoplasm arising from the anus. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the anus. It is characterized by a proliferation of neoplastic spindle cells.
A usually large cell non-Hodgkin lymphoma of B-cell phenotype, arising from the anus. Lymphomas originating from the anal region are rare in the general population, but they are seen with a higher frequency in HIV-positive patients, particularly homosexual men.
A basal cell carcinoma arising from the perianal skin. Local excision is the treatment of choice. Metastases are extremely rare.
An intraepithelial adenocarcinoma originating in the anal margin and characterized by presence of typical Paget's cells, appearing as large rounded vacuolated cells.
A precancerous neoplastic intraepithelial process involving the squamous epithelium of the perianal skin. Clinically, it usually presents as a white or red area in the perianal skin. Morphologically, it is characterized by full thickness dysplasia of the squamous epithelium and sometimes of the pilosebaceous epithelium. Human papillomavirus DNA sometimes may be identified in the dysplastic epithelium. It may recur after treatment, however only a small percentage of cases progress to squamous cell carcinoma.
An anal adenocarcinoma characterized by the presence of mucoid stroma formation.
A neoplasm with neuroendocrine differentiation that arises from the anal canal. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A slowly spreading, erythematous eczematoid plaque in the anal region. Histologically, the basal part or whole thickness of the squamous epithelium is infiltrated by large cells with abundant pale cytoplasm and large nuclei. Half of the cases are associated with an internal malignancy, most often a colorectal adenocarcinoma. The other half of the cases, have a high local recurrence rate and they may become invasive (WHO).
A malignant mesenchymal tumor with skeletal muscle differentiation affecting the anus.
A malignant soft tissue neoplasm arising from the anus. Representative examples include leiomyosarcoma, rhabdomyosarcoma, and Kaposi sarcoma.
A large, well differentiated squamous cell carcinoma with a cauliflower-like appearance, characterized by the presence of an exophytic and endophytic growth pattern. Morphologically, there is papillomatosis and acanthosis present, however cytologically the neoplastic squamous cells have a benign appearance. Dysplastic changes are minimal. It does not respond to conservative treatment and it is regarded by many authors as an intermediate lesion between condyloma acuminatum and squamous cell carcinoma.
An anaplastic astrocytoma that arises from the cerebral hemispheres.
An anaplastic meningioma that arises within the cranial cavity.
An anaplastic (malignant) meningioma involving the spinal meninges.
Wilms tumor of the kidney characterized by the presence of nuclear anaplasia. Anaplasia is defined by the presence of all of the following: multipolar polyploid mitotic figures, marked nuclear enlargement, and hyperchromasia. When anaplasia is diffuse, it is associated with an unfavorable clinical outcome.
An angiosarcoma that develops in association with long standing lymphedema.
A meningioma that affects the anterior cranial fossa.
A meningioma that affects the anterior foramen magnum.
An adenoid cystic carcinoma arising from the minor salivary glands in the anterior tongue.
A carcinoma that arises from the anterior two-thirds of the tongue. Representative examples include squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma.
A mucoepidermoid carcinoma arising from the minor salivary glands in the anterior tongue.
A benign or malignant neoplasm that affects the anterior portion of the tongue.
A meningioma that affects the anterior visual pathway.
Inflammation of the glomeruli secondary to presence of autoantibodies directed at specific antigenic targets within the glomerular basement membrane, causing hematuria, proteinuria, and impaired renal function.
A malignant vascular neoplasm arising from the aorta.
Breast adenosis characterized by the presence of extensive apocrine metaplasia.
A ductal breast carcinoma in situ, characterized by the presence of neoplastic epithelial cells with apocrine differentiation.
An adenocarcinoma of the breast characterized by the presence of two intermingled cellular components: cells with abundant granular, eosinophilic cytoplasm, and cells with abundant cytoplasm containing fine empty vacuoles.
A benign or malignant sweat gland neoplasm with apocrine differentiation. Representative examples include apocrine adenoma, ceruminous adenocarcinoma, and apocrine breast carcinoma.
A hamartoma characterized by localized apocrine sweat gland malformation.
A well-circumscribed benign smooth muscle neoplasm arising from the appendix. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A lymphoma arising from the appendix. The majority of lymphomas affecting the appendix represent disease extension from the intestinal wall; primary lymphomas of the appendix are rare.
An adenoma arising from the appendix. It is characterized by the presence of villous epithelial structures and it is associated with dysplasia.
Severe cellular and nuclear atypia in the cells of the endometrial glands. It often occurs during gestation, gestational trophoblastic disease, and treatment with gonadotropins or high doses of progestins.
A carcinoma arising in the lung due to exposure to asbestos.
Malignant mesothelioma occurring in a patient exposed to asbestos.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the ascending colon. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A bone osteosarcoma affecting multiple skeletal sites, with multifocal lesions discovered between 6 and 24 months after the appearance of the initial tumor. Patients with asynchronous tumors have a better prognosis than those with synchronous osteosarcomas.
A benign or malignant extra-adrenal paraganglioma arising from paraganglia located in the cardiac atrium.
A condition in which deposits of fat accumulate within the interatrial septum.
A preinvasive lesion in the lung. It is characterized by the presence of a small, localized proliferation of mildly to moderately atypical type II pneumocytes and/or Clara cells lining alveolar walls and sometimes respiratory bronchioles.
An intraductal papilloma of the breast characterized by the presence of focal epithelial atypia.
A neoplastic process that arises from the terminal ductal lobular unit of the breast parenchyma. It is usually solitary and confined to a single lobular unit. It is characterized by the presence of a monomorphic epithelial proliferation in a cribriform, micropapillary, or solid growth pattern. Focal architectural features of low grade ductal carcinoma in situ are present. There is an increased risk for development of invasive breast carcinoma.
A morphologic finding indicating the presence of atypical mitoses in malignant cells.
Focal proliferation of small acinar glandular cells in the prostate gland with cytologic changes ranging from atypia to highly suggestive of malignancy.
Benign and malignant neoplasms which arise from or directly involve the central or peripheral elements of the autonomic nervous system.
A B-cell lymphoproliferative disorder with uncertain malignant potential. The representative example of this category is lymphomatoid granulomatosis.
Kidney dysfunction resulting from complications of bone marrow transplantation.
An autosomal dominant inherited syndrome caused by mutations in the BRCA1 gene. Patients are at high risk of developing breast cancer, ovarian cancer, and other cancers including cervical, endometrial, fallopian tube, and colon cancer.
An autosomal dominant inherited syndrome caused by mutations in the BRCA2 gene. Patients are at high risk of developing female and male breast cancer, ovarian cancer, and other cancers including prostatic cancer, pancreatic cancer, gastric cancer, and melanoma.
An adenocarcinoma arising from Barrett metaplastic epithelium in the esophagus. There is evidence supporting the idea that the Barrett adenocarcinomas develop through a stepwise progression through intestinal metaplastic epithelium to epithelial dysplasia to malignancy. Adenocarcinomas arising in the setting of Barrett esophagus are typically papillary and/or tubular. In terms of grading, they are well or moderately differentiated adenocarcinomas. -- 2002
An aggressive, human papillomavirus-related squamous cell carcinoma that arises from the penis. It is characterized by the presence of nests of small malignant cells. The malignant cells tend to invade deeply into the adjacent tissues. Comedo-type necrosis is often present.
A large cell lung carcinoma characterized by the presence of a solid nodular or anastomotic trabecular growth pattern, peripheral palisading, and comedo type necrosis.
A rare primary thymic carcinoma, characterized by the presence of tumor cell lobules with peripheral palisading, and a basophilic staining pattern. More than half of reported cases were associated with the presence of a multilocular thymic cyst. Metastases to lung and liver have been reported in approximately 30% of cases.
An ameloblastoma that does not recur or metastasize.
A non-metastasizing neoplasm arising from the anus. It is characterized by the presence of large polygonal cells with abundant granular cytoplasm.
A non-metastasizing neoplasm that arises from the anterior portion of the tongue.
A non-metastasizing cardiac neoplasm that arises from the right or left atrium.
A benign, nodular tumor that arises from the breast parenchyma. It is characterized by the proliferation of myoepithelial cells around spaces that are lined by epithelial cells. Occasionally, adenomyoepitheliomas may undergo malignant transformation.
A non-metastasizing germ cell tumor that arises within the myocardium or cardiac chambers.
A benign peripheral nervous system neoplasm that is composed of well-differentiated Schwann cells and affects the heart.
A non-metastasizing mesenchymal, non-meningothelial neoplasm that arises from the central nervous system.
A non-metastasizing neoplasm that arises from the brain during childhood.
A non-metastasizing neoplasm that arises from the central nervous system during childhood.
A non-metastasizing neoplasm that arises from the cerebral hemispheres during childhood.
A non-metastasizing germ cell tumor that occurs during childhood.
A non-metastasizing neoplasm that arises from the supratentorial region of the brain during childhood.
A very rare, benign sweat gland neoplasm that affects the breast. It is characterized by the proliferation of basaloid epithelial cells.
A non-metastasizing eccrine appendage sweat gland neoplasm. Representative examples include hidrocystoma, syringoma, and syringofibroadenoma.
A slowly growing, benign, usually encapsulated neoplasm arising from the esophagus. Morphologically, it is composed of neoplastic differentiated Schwann cells.
A non-metastasizing germ cell tumor that arises from an anatomic site other than the testis or ovary.
A non-metastasizing mesenchymal neoplasm that arises from the extrahepatic bile ducts. Representative examples include leiomyoma and lipoma.
A non-metastasizing neoplasm that arises from the extrahepatic bile ducts tissues, excluding the epithelial tissue.
A benign mesenchymal neoplasm with cartilaginous or osseous differentiation arising from the soft tissues exclusively. Representative examples include chondroma and osteoma.
A benign mesenchymal neoplasm composed of fibrohistiocytic cells, spindle fibroblastic cells, and histiocytes, in a storiform pattern.
A benign mesenchymal neoplasm characterized by the presence of neoplastic fibroblasts without malignant characteristics.
A non-metastasizing neoplasm arising from the gallbladder. It is characterized by the presence of large polygonal cells with abundant granular cytoplasm.
A non-metastasizing neoplasm arising from the gastric wall. It is characterized by the presence of large polygonal cells with abundant granular cytoplasm.
A non-metastasizing mesenchymal neoplasm of the stomach. Representative examples include leiomyoma, lipoma, and hemangioma.
A germ cell tumor without metastatic potential.
A glomus tumor of small size characterized by the absence of nuclear atypia and mitotic activity.
A benign granular cell tumor that arises from the extrahepatic bile ducts.
A grade I, slowly growing meningioma within the cranial cavity.
A benign hemangiopericytoma arising from the kidney.
A benign, solid or cystic germ cell tumor that arises from the mediastinum. Solid tumors are classified as benign teratomas. Cystic tumors are classified as dermoid cysts.
A benign hemangiopericytoma arising from the mediastinum.
A schwannoma that arises from the posterior mediastinum. It is characterized by the presence of psammoma bodies.
A non-metastasizing mesenchymal neoplasm that arises from the mediastinum. Representative examples include lipoma, leiomyoma, and rhabdomyoma.
A benign soft tissue tumor in which the line of differentiation is uncertain.
A cystically dilated epithelial neoplasm arising from the appendix. It is characterized by the presence of a cystic structure that is filled with mucus.
A non-metastasizing neoplasm that arises in the area of the nipple.
A non-metastasizing neoplasm arising from the gallbladder wall. The neoplastic process does not involve the epithelial layer. Representative examples include leiomyoma, lipoma, and neurofibroma.
A benign non-epithelial neoplasm that affects the liver parenchyma and intrahepatic bile ducts. Representative examples include hemangioma, angiomyolipoma, and solitary fibrous tumor.
A benign hemangiopericytoma arising from the orbit.
A non-metastasizing bone-forming neoplasm. This category includes osteoma, osteoid osteoma, and osteoblastoma.
A non-metastasizing thecoma of the ovary that is characterized by the presence of lutein cells.
A non-metastasizing mixed epithelial neoplasm that arises from the ovary. It is characterized by the presence of more than one epithelial cell type, most often serous and endocervical-type mucinous. This category includes seromucinous cystadenoma and seromucinous adenofibroma.
A non-metastasizing neoplasm that arises from the ovary and is characterized by the presence of neoplastic epithelium that resembles the epithelium of the fallopian tube. It includes serous cystadenoma, serous adenofibroma, serous cystadenofibroma, and surface papilloma.
A sex cord-stromal tumor arising from the ovary, without metastatic potential.
A thecoma of the ovary that does not metastasize to other anatomic sites.
A benign mesenchymal neoplasm arising from the perivascular cells of the connective and soft tissues. It is characterized by the presence of pericytes that grow in a circumferential pattern around vessels.
A usually unilateral, benign and well circumscribed biphasic neoplasm that arises from the breast. It usually affects middle-aged women. It is characterized by the presence of a double layer of epithelial cells that are arranged in clefts, surrounded by a cellular, monomorphic spindle cell mesenchymal component. Mitoses are rare. Necrotic changes may be present in large tumors.
A rare benign neoplasm that arises from the prostate gland and is characterized by the presence of hyperplastic glands and stroma that contains spindle-shaped cells.
A non-metastasizing neoplasm that arises from the male or female reproductive system. Representative examples include benign prostate phyllodes tumor, benign Sertoli cell tumor, uterine corpus leiomyoma, and benign ovarian serous tumor.
A rare benign tumor composed of sheets and islands of spindle, plasmacytoid, epithelioid, and clear cells that exhibit myoepithelial but not ductal differentiation. The average age of patients has been reported as 44 years. Clinically, these tumors present as asymptomatic masses. Discrimination between myoepithelioma and myoepithelial carcinoma is based primarily on the infiltrative growth of the latter.
A benign mesenchymal neoplasm arising from skeletal muscle tissue.
A benign mesenchymal neoplasm arising from smooth muscle tissue.
A non-metastasizing sex cord-stromal tumor that arises from the testis. Morphologically, it is characterized by the presence of Sertoli cells forming tubules. Leydig cells are rare or absent.
A non-metastasizing neoplasm that arises from the uterine corpus and is composed of epithelial and mesenchymal elements. Representative examples include adenomyoma and adenofibroma.
Cancer that occurs in both of a pair of organs, such as both breasts, ovaries, eyes, lungs, kidneys, or adrenal glands, at the same time.
Meningiomas that affects both optic nerves.
A mucoepidermoid carcinoma that arises from the extrahepatic bile ducts.
A pulmonary blastoma composed of a mixture of irregular tubular structures and mesenchymal elements.
A rare morphologic variant of bladder adenocarcinoma characterized by the presence of malignant glandular epithelial cells and clear cells distributed in a tubulo-cystic, papillary, or diffuse pattern. There is a female predilection. Clinical presentation includes hematuria and dysuria.
A non-papillary neoplasm of the urinary bladder, whose classification categories include low-grade intraurothelial neoplasia and urothelial carcinoma in situ.
A well-circumscribed benign smooth muscle neoplasm arising from the bladder. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A benign or malignant extra-adrenal sympathetic paraganglioma arising from the urinary bladder. Clinical signs include hypertension and hematuria.
A highly aggressive carcinoma, histologically resembling small cell lung carcinoma. In most cases it is associated with carcinoma in situ.
A granulocytic sarcoma composed primarily of myeloblasts (WHO 2001).
A distinct subtype of high-grade follicular center cell lymphoma, representing a diffuse transformation of conventional follicular lymphoma. Although this type of lymphoma strongly expresses BCL-2, it does not carry the characteristic t(14;18)(q32;q21) chromosomal translocation found in follicular lymphomas. Instead, extra copies of chromosome 18 are often detected.
An aggressive mantle cell lymphoma characterized by the presence of neoplastic B-lymphocytes resembling lymphoblasts.
Breast adenosis characterized by the presence of ducts with distended lumen and columnar cell metaplasia.
A high-grade malignant vascular neoplasm that arises from the bone. It is characterized by the presence of neoplastic cells with endothelial differentiation.
A locally aggressive hemangioma that arises from the bone. It is characterized by the presence of epithelioid endothelial cells.
A benign or malignant glomus tumor arising from the bone.
A rare aggressive malignant smooth muscle neoplasm, arising from the bone. It is characterized by a proliferation of neoplastic spindle cells.
A benign neoplasm which is composed of adipocytes and arises from the surface of the bone or the medullary cavity.
A very rare malignant adipose tissue neoplasm that arises from the bone.
A rare non-Hodgkin lymphoma or even more rarely, a Hodgkin lymphoma that arises from the bone, without lymph node or other extranodal involvement. The femur, spine, and pelvic bones are the most commonly affected sites. The majority of patients present with bone pain in the affected area. A single bone or multiple skeletal sites may be involved. The prognosis is related to the cell type and the stage of the disease.
A usually aggressive malignant bone-forming mesenchymal neoplasm arising from the surface of the bone.
A phyllodes tumor of the breast characterized by the presence of intermediate features and a stroma which usually resembles low grade fibrosarcoma.
A group of epithelial neoplasms that arise from the exocrine pancreatic tissue and have the potential to evolve into invasive malignant neoplasms. This group includes the pancreatic intraepithelial neoplasias, non-invasive pancreatic mucinous-cystic neoplasms, pancreatic intraductal papillary-mucinous neoplasms, and pancreatic intraductal tubulopapillary neoplasms.
A lesion characterized by the presence of atypical or low-grade neoplastic cells, which may or may not exhibit stromal microinvasion and cannot be qualified as completely malignant.
An epithelial neoplasm that arises from the ovary characterized by the presence of cystic spaces which are lined by atypical glandular epithelial cells resembling endometrial cells. The surrounding ovarian stroma is fibrotic. There is no evidence of stromal invasion.
A low grade, non-invasive mixed epithelial proliferative neoplasm that arises from the ovary and is composed of more than one epithelial cell type, most often serous and endocervical-type mucinous.
A low grade serous epithelial neoplasm arising from the ovary. It is characterized by an atypical proliferation of serous-type epithelial cells without evidence of stromal invasion. It is often asymptomatic but rarely it may present with abdominal pain or abdominal enlargement due to rupture or torsion.
An astrocytoma that arises from the brain stem.
An ependymoma that arises from the brain stem.
A malignant, clinically aggressive astrocytic tumor (glioma) localized in the brain stem. -- 2003
A morphologic variant of meningioma arising from the brain stem. It is characterized by the presence of clear glycogen-rich polygonal cells.
An invasive breast carcinoma characterized by the presence of a predominant squamous cell component that is admixed with the adenocarcinoma component.
A malignant vascular neoplasm arising from the breast.
A capillary hemangioma arising from the breast.
A carcinoma that arises from the breast and has metastasized to the bone.
A carcinoma that has spread to the brain from its original site in the breast, through the hematogenous route.
A carcinoma that originates from the breast and has spread to the liver.
A carcinoma that arises from the breast and has metastasized to the lung.
A hemangioma characterized by the presence of epithelioid endothelial cells, arising from the breast.
Breast fibrocystic change characterized by the absence of epithelial cell hyperplasia.
Breast fibrocystic change characterized by the presence of epithelial cell hyperplasia. Epithelial atypia may be present or absent.
A usually aggressive malignant neoplasm arising from the breast. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
An aggressive malignant smooth muscle neoplasm, arising from the breast. It is characterized by a proliferation of neoplastic spindle cells.
A malignant adipose tissue neoplasm of the breast.
An extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue that arises from the breast as a primary tumor.
A neoplasm that arises from the breast and is composed of cells of neuroendocrine origin. Most cases are neuroendocrine carcinomas. Primary carcinoid tumors of the breast are very rare.
A benign breast neoplasm characterized by the proliferation of multiple papillomas.
A malignant mesenchymal tumor with skeletal muscle differentiation affecting the breast.
A small cell carcinoma that arises from the breast. The morphologic and immunohistochemical features are identical to those seen in the small cell carcinoma of the lung.
A benign adenomatous neoplasm that arises from the mucous glands in the bronchus.
A benign, exophytic and polypoid growth that arises from the buccal mucosa. It is covered by hyperplastic epithelium. Some cases are caused by human papillomavirus infection.
Burkitt lymphoma characterized by the presence of malignant cells with eccentric basophilic cytoplasm. The nucleoli of these cells are often single and central. This morphologic variant of Burkitt lymphoma is more often seen in patients with immunodeficiency.
A rare genetic disorder with an autosomal recessive pattern of inheritance. It is caused by the ineffective or decreased biosynthesis of the third complement component, C3. C3 deficiency may also be acquired acutely post-infection or chronically from co-morbid autoimmune disorders. If C3 is adequately synthesized, its rapid depletion may result in a functional deficiency. Clinical signs of the inherited deficiency present within the first decade of life and are consistent with the signs of recurrent systemic infection or immune complex disease. Deficiency of serum C3 and its major cleavage product, C3b, will decrease the effective humoral immune response to encapsulated bacteria. Deficiency of C3 also impairs clearance of circulating immune complexes and therefore predisposes to rheumatic and renal disease.
A non-Hodgkin lymphoma arising from the anus and occurring in HIV-positive patients. Homosexual HIV-positive men have an increased risk of developing anal non-Hodgkin lymphoma in comparison to the general male population. The majority of the cases are large cell lymphomas of B-cell phenotype.
A benign well-circumscribed paucicellular lesion arising from the soft tissues. It is characterized by the presence of fibroblasts, lymphoplasmacytic infiltrates, collagenous stroma formation, psammoma bodies, and dystrophic calcifications.
A debilitating tiredness or total lack of energy, often reported as the most common symptom in individuals with cancer. Cancer fatigue can result from chemotherapy, radiation therapy, surgery, and other treatments; chemotherapy-induced anemia is a very frequent cause. -- 2004
A carcinoid tumor that arises from the breast. Primary carcinoid tumors of the breast are rare; most cases represent metastases from other anatomic sites.
A rare squamous cell carcinoma that either arises from or is associated with the presence of inverted papilloma in the nose.
An aggressive, high grade malignant tumor that arises from the salivary gland. It is characterized by the presence of a malignant epithelial and a sarcomatous component.
A usually aggressive malignant neoplasm arising from the heart. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
A very rare granular cell tumor that arises from the heart.
A low-grade malignant blood vessel neoplasm, arising from the heart. IIt is characterized by the presence of epithelioid endothelial cells. The neoplastic cells are arranged in cords and nests, which are embedded in a myxoid to hyalinized stroma.
A Kaposi sarcoma arising from the heart.
An aggressive malignant smooth muscle neoplasm, arising from the heart. It is characterized by a proliferation of neoplastic spindle cells.
A rare benign adipose tissue neoplasm of the heart usually originating in the epicardial or pericardial fatty tissue.
An extranodal lymphoma that arises from the heart and/or the pericardium. The majority of the cases are diffuse large B-cell lymphomas. Patients may present with chest pain, heart failure, pericardial effusion, arrhythmia, or syncope.
A benign or malignant extra-adrenal paraganglioma arising from paraganglia located in the heart.
A benign tumor of cardiac striated muscle.
An extra-adrenal spinal paraganglioma arising from the cauda equina. It should not be confused with glomus coccygeum, a structure unrelated to paraganglia. Clinically, it may be asymptomatic or present with cauda equina syndrome, lower back pain, or leg pain.
A cavernous hemangioma arising from the face.
A meningioma that affects the cavernous sinus.
An adenocarcinoma arising from the cecum. It is more frequently seen in populations with a Western type diet and in patients with a history of chronic inflammatory bowel disease. Histologic variants include mucinous adenocarcinoma, signet ring cell carcinoma, medullary carcinoma, serrated adenocarcinoma, cribriform comedo-type adenocarcinoma, and micropapillary adenocarcinoma.
An extranodal lymphoma that arises from the cecum. The majority are B-cell non-Hodgkin lymphomas.
An extranodal non-Hodgkin lymphoma that arises from the cecum. The majority are B-cell non-Hodgkin lymphomas.
A neoplasm that arises from the glandular epithelium of the cecal mucosa. It is characterized by a villous architectural pattern. The neoplastic glandular cells have dysplastic features.
A malignant vascular neoplasm arising from the brain, spinal cord or meninges.
A malignant germ cell tumor of the central nervous system characterized by extra-embryonic differentiation along trophoblastic lines. The diagnosis requires the identification of cytotrophoblastic elements, as well as syncytiotrophoblastic giant cells. (WHO)
A central nervous system multilobular lesion, characterized by a thick wall. The Intramural contents are soft and waxy with a variable amount of cholesterol. Teeth are rarely present though hair is not uncommon.
A usually aggressive malignant neoplasm arising from the central nervous system. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
A unique group of rare tumors of the central nervous system that affect mainly children and adolescents. Their morphologic and biologic profile corresponds to that of homologous germ cell tumors that arise in the gonads and in other extragonadal sites. Representative examples include: germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma.
A primary or metastatic neoplasm of hematopoietic origin that affects the brain, meninges, or spinal cord. Representative examples include Hodgkin and non-Hodgkin lymphomas, histiocytic tumors, and leukemias.
A variant of teratoma composed of incompletely differentiated components resembling fetal tissues. Even if the immature component is only a minor element of an otherwise differentiated teratoma, the tumor is still classified as immature. (Adapted from WHO)
Leukemia infiltrating the central nervous system structures.
A rare benign adipose tissue neoplasm of the central nervous system frequently found in midline locations such as the corpus callosum, the quadrigeminal plate, the hypothalamus, the spinal canal or the cauda equina. Some contain Schwann cells, bone, cartilage or hamartomatous blood vessels.
A teratoma composed exclusively of fully differentiated, 'adult-type' tissue elements that are sometimes arranged in a pattern resembling normal tissue relationships. Mitotic activity is low or absent. The more common ectodermal components present in a mature teratoma include skin, brain and choroid plexus. The more common mesodermal components include cartilage, bone, fat and muscle (both smooth and striated). And the most common endodermal components are cysts lined by epithelia of respiratory or enteric type and in some cases pancreatic or hepatic tissue. (Adapted from WHO)
A primary tumor of the central nervous system that arises from leptomeningeal melanocytes. It may present as a diffuse proliferative leptomeningeal process (often as a component of the neurocutaneous melanosis complex) or as a distinct mass lesion.
A melanoma that affects the central nervous system. It is characterized by pleomorphism, melanin pigmentation, a high mitotic rate, necrosis, and hemorrhage. It is a highly aggressive and radioresistant tumor. The prognosis is usually poor.
A benign or malignant extra-adrenal paraganglioma arising from the central nervous system.
A malignant mesenchymal neoplasm with skeletal muscle differentiation affecting the central nervous system.
A sarcoma that arises from the central nervous system.
A benign or malignant mesenchymal neoplasm originating in the central nervous system or the meninges and showing fibrous, fibrohistiocytic, adipose, myoid, endothelial, chondroid or osseous, but not meningothelial differentiation. Depending on the histological features and clinical behavior of these neoplasms, their grade ranges from benign (WHO grade I) to highly malignant (WHO grade IV). (Adapted from WHO)
A T-cell lymphoblastic lymphoma or a mature T-cell and NK-cell neoplasm that affects the brain, meninges, or spinal cord.
A mature or immature teratoma that affects the central nervous system.
A benign papillary neoplasm that arises in a large duct of the breast. It is characterized by the presence of a fibrovascular core that is lined by benign epithelial and myoepithelial proliferations. Patients usually present with nipple discharge.
A papillary meningioma that affects the cerebellum.
A medulloblastoma arising from the vermis of the cerebellum.
A central nervous system embryonal tumor, not otherwise specified arising from the cerebellopontine angle of the infratentorial brain.
A rare benign adipose tissue neoplasm within the cerebral hemisphere often associated with partial or complete agenesis of the corpus callosum.
A Hodgkin lymphoma that arises from the cerebral hemispheres as a primary lesion.
A non-Hodgkin lymphoma that arises in the cerebral hemispheres as a primary lesion.
An adenoma or carcinoma that arises from the ceruminous glands in the external auditory canal.
A rare carcinoma that arises from the cervix. It is characterized by the presence of cystic spaces surrounded by palisaded epithelial cells. The cystic spaces contain eosinophilic hyaline material or mucin. Nuclear pleomorphism, necrotic changes, and a high mitotic rate are also present.
A rare morphologic variant of cervical adenocarcinoma composed of clear and hobnail cells. It is associated with in utero exposure to diethylstilbestrol (DES).
A cervical adenocarcinoma with the histologic characteristics of the endometrioid adenocarcinoma of the endometrium.
A meningioma that arises from the meninges of the cervical region of the spinal cord.
An aggressive malignant mixed epithelial and mesenchymal neoplasm that arises from the cervix and is characterized by the presence of malignant epithelial elements and malignant mesenchymal elements.
A benign endocervical polypoid epithelial hyperplasia characterized by the presence of tightly packed glandular structures. It is usually seen in women on oral contraceptive therapy and during pregnancy.
A usually well to moderately differentiated cervical adenocarcinoma characterized by the presence of malignant glandular cells that contain significant amount of intracytoplasmic mucin.
A non-neoplastic disorder that affects the cervix. Representative examples include endometriosis and cervicitis.
A neoplastic process that affects the squamous epithelium of the cervix. It is classified as cervical squamous intraepithelial neoplasia 1, 2, or 3, according to the degree of squamous cell maturation and cellular atypia, and the number of mitotic figures.
A non-neoplastic or neoplastic disorder that affects the structures of the chest wall. Representative examples include infection, chest wall lipoma, and chest wall lymphoma.
An extraabdominal fibromatosis arising from the soft tissue of the chest wall. It is characterized by the presence of elongated spindle-shaped fibroblasts, collagenous stroma formation, and an infiltrative growth pattern.
A Hodgkin lymphoma that affects the structures of the chest wall.
A benign adipose tissue neoplasm of the chest wall.
A lymphoma that affects the structures of the chest wall. The majority of cases are diffuse large B-cell lymphomas.
A parachordoma arising from the chest wall.
An intermediate cutaneous fibrohistiocytic neoplasm arising from the chest wall. It is a multinodular poorly circumscribed tumor, characterized by the presence of multinucleated giant cells, mononuclear histiocyte-like cells, and spindle fibroblast-like cells arranged in a plexiform pattern.
A solitary plasmacytoma that arises from the chest wall.
An acute erythroid leukemia occurring in children.
An acute monoblastic and monocytic leukemia occurring in children.
An anaplastic large cell lymphoma that occurs during childhood.
An anaplastic oligodendroglioma that arises from the central nervous system and occurs during childhood.
A morphologic variant of embryonal rhabdomyosarcoma occurring in children. The tumor arises from organs with a mucosal epithelial surface. It is characterized by the formation of a cambium layer in the affected tissue and polypoid nodules within an abundant myxoid stroma.
A morphologic variant of embryonal rhabdomyosarcoma occurring in female children. The neoplasm arises from the vagina. It is characterized by the formation of a cambium layer in the affected tissue and polypoid nodules with an abundant myxoid stroma.
A morphologic variant of embryonal rhabdomyosarcoma occurring in female children. The neoplasm arises from the vulva. It is characterized by the formation of a cambium layer in the affected tissue and polypoid nodules with an abundant myxoid stroma.
An anaplastic astrocytoma that arises from the brain and occurs during childhood.
A germinoma arising from the brain during childhood.
A brain meningioma that occurs during childhood.
An astrocytoma that arises from the brain stem and occurs during childhood.
A neoplasm that affects the brain stem and occurs during childhood.
A germinoma arising from the central nervous system during childhood.
An immature teratoma that arises from the central nervous system and occurs during childhood.
A mature teratoma that arises from the central nervous system during childhood.
A mixed germ cell tumor that arises from the central nervous system and occurs during childhood.
A central nervous system embryonal tumor, not otherwise specified that occurs in childhood.
A neoplasm that affects the cerebellum and occurs during childhood.
A diffuse astrocytoma that arises from the cerebral hemispheres and occurs during childhood.
An embryonal tumor with multilayered rosettes, C19MC-altered that arises from the cerebral hemispheres and occurs in children.
A choroid plexus papilloma that arises in the brain during childhood.
A rare malignant neoplasm with melanocytic differentiation characterized by the presence of polygonal or spindle shaped clear cells affecting children. This sarcoma usually affects the tendons and aponeuroses and is associated with a poor prognosis due to recurrences and metastases.
A low grade childhood congenital malignant neoplasm arising from the kidney. It is characterized by the presence of fibroblastic cells. The majority of cases occur in the first year of life. Complete excision is usually associated with an excellent prognosis.
A desmoplastic small round cell tumor occurring in children.
A diffuse large B-cell lymphoma that occurs during childhood.
An osteosarcoma arising from the soft tissue, and occurring during childhood.
A ganglioglioma that arises from the central nervous system and occurs during childhood.
A benign or malignant neoplasm of the liver parenchyma and intrahepatic bile ducts that occurs during childhood.
An embryonal tumor with multilayered rosettes, C19MC-altered that arises from the infratentorial region and occurs in children.
A neoplasm that affects the infratentorial region of the brain and occurs during childhood.
A high grade malignant bone-forming mesenchymal neoplasm that produces osteoid and occurs in childhood. It arises from the medullary portion of the bone. It affects the long bones, and most commonly, the distal femur, proximal tibia, and proximal humerus. Pain with or without a palpable mass is the most common clinical presentation. It usually has an aggressive growth and may metastasize through the hematogenous route. The lung is the most frequent site of metastasis.
A neoplasm that arises within the skull and occurs during childhood.
A melanoma that arises from leptomeningeal melanocytes and occurs in childhood.
An acute or chronic leukemia that occurs during childhood.
Lymphocyte-rich classical Hodgkin lymphoma occurring in childhood.
A Hodgkin or non-Hodgkin lymphoma that occurs during childhood.
A mature T- and NK-cell non-Hodgkin lymphoma that occurs during childhood.
A mesenchymal chondrosarcoma occurring in children.
A cystic neoplasm which arises from the kidney and occurs in children. It includes the cystic partially differentiated nephroblastoma and cases in which nephroblastomatous elements are not present.
A myxoid chondrosarcoma occurring in children.
A nodular lymphocyte predominant Hodgkin lymphoma occurring in children.
A non-gestational choriocarcinoma that arises from the ovary and occurs in children.
A dysgerminoma that arises from the ovary and occurs in children.
An embryonal carcinoma that arises from the ovary and occurs in children.
An immature teratoma that arises from the ovary and occurs in children.
A mature teratoma that arises from the ovary and occurs in children.
A mature or immature teratoma that arises from the ovary and occurs in children.
A yolk sac tumor that arises from the ovary and occurs in children.
A low grade malignant bone-forming mesenchymal neoplasm arising from the surface of the bone. It occurs in childhood and usually affects the distal posterior femur, the proximal tibia, and proximal humerus. Painless swelling is the usual clinical sign. The prognosis is usually excellent.
A pilocytic astrocytoma that occurs during childhood.
A B lymphoblastic lymphoma that occurs during childhood.
A T lymphoblastic leukemia/lymphoma that occurs during childhood.
A T lymphoblastic lymphoma that occurs during childhood.
An anaplastic large cell lymphoma that occurs during childhood and is limited to the skin at the time of diagnosis.
An angiomyolipoma occurring in childhood.
A renal cell carcinoma that occurs during childhood.
A neoplasm that affects the supratentorial region of the brain and occurs during childhood.
A systemic anaplastic large cell lymphoma that occurs during childhood.
A choriocarcinoma that arises from the testis during childhood.
An embryonal carcinoma that arises from the testis during childhood.
A malignant testicular mixed germ cell neoplasm that occurs during childhood. It is characterized by the presence of embryonal carcinoma and teratoma components.
A malignant mixed germ cell neoplasm that arises from the testis during childhood.
A neoplasm that arises from the testis during childhood.
A teratoma that arises from the testis during childhood.
A yolk sac tumor that arises from the testis during childhood.
An astrocytoma that arises from the visual pathway and occurs during childhood.
A Wilms tumor of the kidney which occurs in children.
A yolk sac tumor that occurs during childhood.
An extraskeletal chondroma usually arising from the dura.
An adult T-cell leukemia/ lymphoma associated with skin lesions and mild lymphadenopathy. Neoplastic lymphocytes are not numerous in the peripheral blood. Hypercalcemia is absent. -- 2004
Chronic pain that results from cancer and/or its treatment. The mechanism for chronic cancer pain may be inflammatory, neuropathic, ischemic, and/or mechanical in nature.
A morphologic finding indicating the presence of reactive lymphocytes, lymphoplasmacytic cells, and/or reactive plasma cells in a tissue sample.
A recently recognized variant of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) expressing somatic hypermutations of the Immunoglobulin heavy chain (IGH) genes. The recognition of this variant alters the belief that CLL/SLL is always derived from a naive, pregerminal center B-cell. The presence of somatic hypermutations of IGH genes occurs in approximately 50% of CLL/SLL cases and implies a postgerminal center, memory origin. Patients with this variant of CLL/SLL have a favorable prognosis, with a reported median survival of more than 24 years.
A recently recognized variant of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) that lacks somatic hypermutations of the Immunoglobulin heavy chain (IGH) genes, implying pregerminal center B-cell origin. Microarray gene expression profiling studies have demonstrated the expression of ZAP-70 gene (Syk family tyrosine kinase) in this subset of CLL/CLL. Patients with this variant of CLL/SLL have an unfavorable prognosis compared to those with somatic hypermutations of the IGH genes, with a median survival of approximately 6-8 years.
Chronic lymphocytic leukemia characterized by the presence of somatic hypermutation within the immunoglobulin heavy chain gene variable region of neoplastic clones. Patients have a better prognosis as compared to those with unmutated immunoglobulin heavy chain gene variable region rearrangements.
A chronic lymphocytic leukemia characterized by the presence of neoplastic lymphocytes with plasmacytoid morphology.
Chronic lymphocytic leukemia characterized by the absence of somatic hypermutation within the immunoglobulin heavy chain gene variable region of neoplastic clones. Patients have a significantly worse prognosis as compared to those with mutated immunoglobulin heavy chain gene variable region rearrangements.
A chronic myelomonocytic leukemia characterized by the presence of less than 10 percent blasts in the bone marrow and less than 5 percent blasts in the peripheral blood.
A chronic myelomonocytic leukemia characterized by the presence of 10-19 percent blasts in the bone marrow and 5-19 percent blasts in the peripheral blood or by the presence of Auer rods regardless of the blasts count.
A chronic myelomonocytic leukemia characterized by a peripheral blood eosinophil count of equal or greater than 1.5x10E9/L, and absence of PDGFRA or PDGFRB gene abnormalities.
This subgroup of myeloproliferative neoplasms includes cases which do not meet the morphologic criteria of any of the defined myeloproliferative neoplasms, or which have characteristics that overlap at least two of the myeloproliferative neoplasms.
A morphologic variant of atypical fibroxanthoma characterized by the presence of atypical mitotic figures, high mitotic activity, and pleomorphic cells.
A benign well-circumscribed tumor, composed of lobules of mature adipocytes, that arises within subcutaneous tissue, deep soft tissues or on the surface of bones.
A Burkitt lymphoma characterized by the presence of a uniform malignant lymphocytic infiltrate that is composed of medium-sized cells with round nuclei and multiple basophilic nucleoli, abundant mitotic figures, and a starry-sky pattern due to the presence of multiple tangible body macrophages.
A monoclonal B-cell lymphoproliferation in the vast majority of cases. It is characterized by a bimodal age distribution (15-30 years of life and late life). Epstein-Barr virus has been postulated to play a role in the pathogenesis of classical Hodgkin lymphoma. Morphologically, it is characterized by the presence of Reed-Sternberg cells and mononuclear Hodgkin cells. The Reed-Sternberg and mononuclear Hodgkin cells are CD30 positive in nearly all cases and CD15 positive in the majority of cases. Four histologic subtypes have been distinguished: lymphocyte-rich, nodular sclerosis, mixed cellularity, and lymphocyte-depleted classical Hodgkin lymphoma.
A rare benign lung tumor with perivascular epithelioid cell differentiation. It is composed of round or oval cells with abundant clear or eosinophilic cytoplasm and distinct cell borders. The vast majority of patients are asymptomatic and the tumors are discovered incidentally. Excision is curative.
A morphologic variant of hepatocellular carcinoma characterized by the presence of clear cells.
A very rare, usually benign neoplasm with perivascular epithelioid cell differentiation characterized by the presence of clear spindle cells arranged in fascicles and nests that usually affects young girls. Patients usually present with a painful abdominal mass.
A rare, usually aggressive, primary thymic carcinoma, characterized by the presence of carcinoma cells with clear cytoplasm.
A carcinoma that arises from the clitoris.
A slow-growing malignant bone tumor arising from the remnants of the notochord and occurring in the clivus. It is characterized by a lobulated growth pattern, myxoid stroma formation, and the presence of physaliphorous cells.
A slow-growing malignant bone tumor arising from the remnants of the notochord and occurring in the clivus. It is characterized by a lobulated growth pattern, myxoid stroma formation, the presence of physaliphorous cells and cartilage.
A carcinoma that arises from the transitional zone at the junction of the rectum and anus.
When radioactive material is used to examine the thyroid with a scanner, nodules that collect less radioactive material than the surrounding thyroid tissue are considered ""cold."" A nodule that is cold does not make thyroid hormone. Cold nodules may be benign or cancerous. Cold nodules are sometimes called hypofunctioning nodules.
An infiltrating pancreatic ductal adenocarcinoma, characterized by the presence of malignant cells floating in pools of mucin. It has a more favorable prognosis than the conventional infiltrating ductal adenocarcinoma. It often arises in association with intraductal pancreatic mucinous neoplasms and in some cases it may result in the development of pseudomyxoma peritonei.
An unusual colon carcinoma characterized by the presence of glandular and squamous carcinomatous components. The two carcinomatous components may be admixed within the tumor, or the two may appear separately in different areas.
A rare Burkitt lymphoma that arises from the colon.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the colon. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A carcinoma that originates from the colonic wall and has spread to the liver.
A cavernous hemangioma arising from the colon.
A ganglioneuroma that arises from the colon. It usually presents as a small mucosal polyp.
An extranodal Hodgkin lymphoma that arises from the colon.
A non-neoplastic hamartomatous polyp that arises from the colon. It is characterized by the presence of tortuous and cystically dilated glands, edematous changes, and inflammation.
A Kaposi sarcoma arising from the colon.
A well-circumscribed benign smooth muscle neoplasm arising from the colon. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm that arises from the colon. It is characterized by a proliferation of neoplastic spindle cells.
A mantle cell lymphoma that arises from the colon. It often presents as a polypoid lesion.
An extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue that arises from the colon.
A neoplasm with neuroendocrine differentiation that arises from the colon. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A malignant soft tissue neoplasm that arises from the colon. Representative examples include angiosarcoma, Kaposi sarcoma, and leiomyosarcoma.
An aggressive, high-grade, and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the colon. It is characterized by the presence of malignant small cells.
A very rare colon carcinoma characterized by the presence of a malignant squamous cell infiltrate.
A well differentiated neuroendocrine tumor that arises from the colon and produces serotonin.
An adenoma that arises from the colon or rectum. It is characterized by the presence of mild epithelial dysplasia.
An adenoma that arises from the colon or rectum. It is characterized by the presence of moderate epithelial dysplasia.
An adenoma that arises from the colon or rectum. It is characterized by the presence of severe epithelial dysplasia.
A gastrointestinal stromal tumor that arises from the colon or rectum. The majority of cases have spindle cell morphology. Gastrointestinal stromal tumors of the colon are usually advanced upon detection and tend to have a poor prognosis; gastrointestinal stromal tumors of the rectum usually have an aggressive clinical course.
A precancerous neoplastic process that affects the colon or rectum. It is characterized by moderate or severe epithelial dysplasia and complex architectural alterations of the mucosal epithelium. There is no evidence of invasion.
A non-neoplastic polypoid lesion in the colon and rectum. It may arise in a background of inflammatory bowel disease or colitis. It is characterized by the presence of a distorted epithelium, inflammation, and fibrosis.
A precancerous neoplastic process that affects the colon or rectum. It is characterized by low or high grade dysplasia of the mucosal epithelium. There is no evidence of invasion.
A well-circumscribed benign smooth muscle neoplasm arising from the colorectal area. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A rare benign adipose tissue neoplasm arising from the wall of the colon and rectum.
A precancerous neoplastic process that affects the colon or rectum. It is characterized by mild epithelial dysplasia and mild architectural alterations of the mucosal epithelium. There is no evidence of invasion.
An adenoma that arises from the colon or rectum. It is characterized by prominent serration of the glands and the presence of generalized low-grade dysplasia.
A usually polypoid neoplasm that arises from the glandular epithelium of the colonic and rectal mucosa. It is characterized by a tubular architectural pattern. The neoplastic glandular cells have dysplastic features.
A neoplasm that arises from the glandular epithelium of the colonic and rectal mucosa. It is characterized by tubular and villous architectural patterns. The neoplastic glandular cells have dysplastic features.
A neoplasm that arises from the glandular epithelium of the colonic and rectal mucosa. It is characterized by a villous architectural pattern. The neoplastic glandular cells have dysplastic features.
A morphologic variant of papillary carcinoma of the thyroid gland characterized by the presence of pseudostratified malignant follicular cells.
A morphologic finding indicating the transformation of non-columnar epithelial cells into columnar cells.
A subtype of large cell neuroendocrine lung carcinoma characterized by the presence of large neuroendocrine cells in combination with adenocarcinoma, squamous cell carcinoma, giant cell carcinoma and/ or spindle cell carcinoma.
A lung carcinoma characterized by the presence of large or small neuroendocrine carcinoma cells in combination with malignant glandular or squamous epithelial cells.
A morphologic variant of small cell lung carcinoma in combination with a non-small cell carcinoma.
A morphologic finding that indicates the presence of a cancerous tumor with a central area that contains necrotic cancer cells.
A breast fibroadenoma that displays fibrocystic changes including apocrine metaplasia, sclerosing adenosis, and cyst formation.
A hyperplasia characterized by excessive proliferation of endometrial cells, resulting in the formation of complex epithelial structures. It is associated with cytologic atypia and an increased risk of endometrial adenocarcinoma.
A hyperplasia characterized by excessive proliferation of endometrial cells, resulting in the formation of complex epithelial structures. Epithelial atypia is absent.
Insomnia that results from a developed tendency to not sleep well under particular conditions.
A genetic disorder that affects the adrenal gland. It includes adrenal gland hyperplasia and adrenal gland hypoplasia.
A broad classification of inherited disorders presenting at birth that affect the initial immunologic response to infection. In these disorders, the primary role of innate immunity to detect and neutralize pathogens which the individual has not been previously exposed is decreased or ineffective.
A broad classification of inherited disorders presenting at birth that affect the cell-mediated aspect of the immune response. Circulating numbers of T lymphocytes are decreased or ineffective.
A non-neoplastic or neoplastic disorder that affects the connective and soft tissue.
An alveolar rhabdomyosarcoma characterized by the presence of large striated muscle cells with clear cytoplasm, giant cells with myoblastic differentiation, and fibrovascular septa.
An angiosarcoma characterized by the presence of malignant spindle endothelial cells.
A malignant mesenchymal neoplasm composed of fibroblasts, and characterized by collagen production and usually a herringbone architectural pattern.
An uncommon, aggressive malignant smooth muscle neoplasm. It is characterized by the presence of atypical large spindle or round cells, nuclear palisading, tumor cell necrosis, mitotic figures and may be associated with vascular invasion.
A malignant hemangiopericytoma characterized by the presence of necrotic changes and in some cases high mitotic activity.
A rare benign adipose tissue neoplasm of the corpus callosum.
A rare self-limiting, rapidly growing, non-encapsulated benign neoplasm that arises from the cranium. This is an osteolytic lesion. It is characterized by the presence of plump spindle-shaped fibroblasts, multinucleated osteoclast-like giant cells, chronic inflammatory infiltrate, red blood cell extravasation, and high mitotic activity.
A morphologic finding indicating the presence of sheets of malignant epithelial cells punctuated by gland-like spaces in a tissue sample.
A benign or malignant neoplasm affecting the skin. The tumor is composed of fibrohistiocytic cells, spindle fibrous cells, and histiocytes in a storiform pattern.
A primary lymphoma of the skin composed of various numbers of small and large irregular neoplastic follicle center cells. Its morphologic pattern can be nodular, diffuse, or nodular and diffuse. It presents with solitary or grouped plaques and tumors, and it usually involves the scalp, forehead, or trunk. It rarely involves the legs. This type of cutaneous lymphoma tends to remain localized to the skin.
A follicular lymphoma involving the skin. A cutaneous follicular lymphoma may be metastatic to the skin from the lymph nodes or other anatomic sites or primary (cutaneous follicle center lymphoma). --2003
Hodgkin lymphoma primarily involving the skin. This diagnosis can only be made when there is no evidence of Hodgkin lymphoma in the lymph nodes or other anatomic sites. Patients usually present with papules or nodular lesions. Morphologically, primary cutaneous Hodgkin lymphoma may resemble lymphomatoid papulosis or anaplastic large cell lymphoma. Immunohistochemical tissue evaluation is essential in establishing the diagnosis. --2003
A benign or malignant adipose tissue neoplasm of the skin.
A malignant adipose tissue neoplasm of the skin.
A malignant vascular neoplasm arising from an area of skin exposed to radiation therapy.
A benign or malignant neoplasm that contains a single or multiple cystic spaces. Examples include cystadenoma, mucinous cystadenocarcinoma, and serous cystadenocarcinoma.
A rare, aggressive odontogenic malignant tumor that arises usually from the mandible and less frequently from the maxilla. It combines the histologic features of an ameloblastoma and carcinoma.
The cellular and vascular changes occurring in the endometrium at the time of implantation.
A morphologic variant of dermatofibrosarcoma protuberans characterized by the presence of poorly differentiated sarcomatous components.
A hemangioma arising from the deep soft tissues.
A rare benign smooth muscle neoplasm arising from deep tissue. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A benign well-circumscribed tumor, composed of mature adipocytes, that arises within deep soft tissues.
A meningioma that is associated with deletion of chromosome 22. This abnormality is the most consistent cytogenetic finding that is detected in meningiomas.
A meningioma that is associated with deletion of chromosomal arm 3p.
A meningioma that is associated with deletion of chromosomal arm 1p.
An infectious process that affects the teeth and/or the periodontal tissues.
A benign neoplasm arising from the dermis. It is characterized by the presence of spindle-shaped fibroblasts.
A morphologic variant of dermatofibrosarcoma protuberans characterized by areas of fibroblastoma like-differentiation, and the presence of giant cells.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the descending colon. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A melanoma of the skin characterized by a proliferation of atypical spindled melanocytes in the dermis, in a background of abundant collagen. It usually presents as an amelanotic raised nodular lesion.
A meningioma that affects the diaphragma sellae.
A granulocytic sarcoma composed of promyelocytes and more mature neutrophils (WHO 2001). --2003
A lymphoma with the morphologic and immunophenotypic features of a follicular lymphoma that shows entirely a diffuse pattern. It is usually seen in small biopsy specimens and most probably represents a diffuse area of a follicular lymphoma.
A very rare condition characterized by generalized proliferation of pulmonary neuroendocrine cells. It manifests as progressive cough and dyspnea. It is considered a precursor for pulmonary carcinoid tumor.
This is usually an oligoclonal CD8+ lymphocytic infiltration of various organs.
A usually aggressive large B-cell lymphoma characterized by the presence of monomorphic immunoblast-like neoplastic B-lymphocytes in a sinusoidal growth pattern. The neoplastic B-lymphocytes express the ALK kinase but they lack the 2;5 translocation.
A biologic subset of diffuse large B-cell lymphomas with a unique molecular signature or expression profile. It represents approximately 50% of diffuse large B-cell lymphomas, and is characterized by the expression of CD10, BCL-6, A-myb, and LMO2 genes, BCL-2 translocation, and c-REL amplification. Morphologically, the vast majority of these lymphomas are centroblastic and a small minority are immunoblastic (ratio20:1). Patients with this type of diffuse large B-cell lymphoma have a more favorable outcome, with a 5-year survival rate of 60% and a median survival of 10 years.
A biologic subset of diffuse large B-cell lymphomas with a unique molecular signature or expression profile. It represents approximately 30% of diffuse large B-cell lymphomas, and is characterized by the expression of CD44, PKCbeta1, Cyclin D2, BCL-2, and IRF4/MUM1 genes. Morphologically, these lymphomas are either centroblastic or immunoblastic (ratio 2:1). Patients with this type of diffuse large B-cell lymphoma are reported to have a less favorable outcome compared to those with a germinal center B-cell expression profile, with a 5-year survival rate of 35% and a median survival of 2 years.
A variant of lymphomatoid papulosis characterized clinically by regressing skin papules, and morphologically by features resembling anaplastic large cell lymphoma.
A neoplastic process characterized by a diffuse poorly circumscribed overgrowth of adipose tissue. It has been associated with several genetic disorders and different clinical conditions such as liver disease, excessive alcohol intake, adrenocortical steroid therapy, and antiretroviral therapy.
A morphologic architectural pattern in which a cellular population is distributed in a relatively uniform fashion throughout a specified tissue area; not focal.
A term that refers to the classification of a disorder according to the anatomic site that is involved in the pathologic process.
An epithelioid sarcoma involving the extremities. It usually presents as nodular masses in the dermis and subcutaneous tissues or in the tendons and fascia. It frequently recurs and metastasizes to other anatomic sites. The most common sites of metastasis are the lungs, lymph nodes, bones, and brain.
An adenocarcinoma that arises from the distal third of the common bile duct.
A carcinoma that arises from the common bile duct distal to the insertion of the cystic duct.
A malignant tumor that has spread from its original (primary) site of growth to another site distant from the primary site.
Abnormal functioning of the small and/or large intestine.
An intradural extramedullary spinal metastasis from an intracranial tumor through the cerebrospinal fluid.
An invasive breast carcinoma characterized by the presence of a predominant squamous cell component that is admixed with the ductal carcinomatous component.
A somatostatin-producing neuroendocrine tumor that arises from the duodenum. It is characterized by the presence of tubulo-glandular structures.
A gastrin-producing neuroendocrine tumor that arises from the duodenum. It is characterized by the presence of uniform cells that form pseudorosettes. The neoplastic cells have uniform nuclei and small amount of eosinophilic cytoplasm.
A neoplasm that arises from the glandular epithelium of the duodenum. It is characterized by a villous architectural pattern. The neoplastic glandular cells have dysplastic features.
Epithelial dysplasia that develops in Barrett esophagus. It is classified as low or high grade. When technical reasons make the interpretation of atypia difficult, atypia is present but it is not quite to the level of dysplasia, or atypia is present at the bases of the crypts but does not reach the surface of the crypts, then the diagnosis of Barrett esophagus-indefinite for dysplasia is made.
A cervical adenocarcinoma with minimal stromal invasion. The risk of local lymph node metastasis is insignificant and the prognosis is excellent.
A cervical squamous cell carcinoma with minimal stromal invasion. The risk of lymph node metastasis is low.
A hamartoma characterized by localized eccrine sweat gland malformation.
A meningothelial neoplasm that arises from an anatomic site outside the intracranial and intraspinal compartments.
A syndrome characterized by abnormal secretion of parathyroid hormone in conjunction with neoplastic growth occurring anywhere in the body.
A condition in which the thymus gland is abnomally located; this can be secondary to failure of descent during fetal development, or failure of involution.
A malignant germ cell tumor of the central nervous system composed of large cells that proliferate in cohesive nests and sheets. In rare occasions, tumor cells may replicate the structure of the early embryo, forming ""embryoid bodies"" replete with germ discs and miniature amniotic cavities. Additional morphologic characteristics include enlarged nucleoli, abundant clear to somewhat violet-hued cytoplasm, a high mitotic rate and zones of coagulative necrosis. (Adapted from WHO)
A malignant neoplasm of embryonal origin, arising from the central nervous system. It usually affects children. Representative examples include ependymoblastoma, medulloblastoma, and atypical teratoid/rhabdoid tumor.
The movement of one cell within another cell (non-phagocytic).
Confined to a specific, localized area and surrounded by a thin layer of tissue.
A thymoma that is confined within the capsule and may display benign or malignant morphologic characteristics.
A Kaposi sarcoma that occurs in adults and children in Equatorial Africa.
A benign neoplasm that arises endobronchially. It is characterized by the presence of mesenchymal tissues admixed with entrapped respiratory epithelium. It presents with signs and symptoms of bronchial obstruction. Bronchoplastic resection is usually curative. Recurrence is very rare.
A benign smooth muscle neoplasm arising endobronchially. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A group of signs, symptoms, and clinicopathological characteristics that result from the pathologic function of one or more endocrine organs.
Patient complaints, physical findings, laboratory findings referable to the endocrinologic system.
A premalignant neoplastic process that affects the endometrial epithelium and glands. It is characterized by architectural glandular alterations and cytological abnormalities in the epithelial cells. The lesion exceeds 1 mm in maximum linear dimension.
A primary carcinoma of the endometrium characterized by the presence of malignant squamous cells.
A well-defined area of unequivocally increased signal intensity on MRI or CT scan images compared with the normal-appearing surrounding tissues, following intravenous injection of gadolinium-based contrast material.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) arising from the gastrointestinal tract. It is characterized by the presence of enterochromaffin-like type granules in the neoplastic cells.
A group of neoplasms which arise from the ependymal lining of the cerebral ventricles and from the remnants of the central canal of the spinal cord. Ependymal tumors occur predominantly in children and young adults with varied morphological features and biological behavior. There are 4 types: ependymoma, anaplastic ependymoma, myxopapillary ependymoma and subependymoma. (WHO)
A rare benign adipose tissue neoplasm of the epicardium of the heart.
A benign epithelial verrucous lesion of the skin. Morphologically, it is characterized by the presence of epidermolytic hyperkeratosis and papillomatosis.
A benign, usually asymptomatic small mesothelial tumor that arises from the epididymis.
An uncommon lipoma characterized by prominent vascularity that arises in the epidural space of the spinal canal.
A meningioma that arises in the epidural spinal canal space.
A disorder seen following cancer chemotherapy. It typically manifests a few years after initiation of epipodophyllotoxin chemotherapy. Mutagenic potential of these non-intercalating DNA topoisomerase II inhibitors is believed to be increased with concurrent use of asparaginase or granulocyte colony-stimulating factor. Balanced translocations involving chromosomal bands 11q23 and 21q22 are commonly associated with this disorder. Clinical signs may include fatigue, dyspnea, bruising and frequent infections. Clinical course usually progresses to acute myeloid leukemia though most epipodophyllotoxin-related leukemias do not have an antecedent myelodysplastic phase. Prognosis is dismal with survivability usually less than one year.
A benign or malignant epithelial neoplasm that affects the liver parenchyma and intrahepatic bile ducts. Representative examples of benign epithelial neoplasms include hepatocellular adenoma and intrahepatic bile duct adenoma. Representative examples of malignant epithelial neoplasms include hepatocellular carcinoma and intrahepatic cholangiocarcinoma.
A non-encapsulated, well defined pulmonary blastoma, composed of irregular tubular structures. It affects mostly middle-aged adults and it is rare in children. The prognosis is better compared to the biphasic pulmonary blastoma.
A uveal melanoma characterized by the presence of malignant large epithelioid melanocytes.
An angiomyolipoma composed exclusively or predominantly by polygonal epithelioid cells with eosinophilic cytoplasm, often associated with cytologic atypia.
Carcinoma that develops in individuals infected with Epstein-Barr virus (EBV), and in which there is a well-documented association between the neoplastic process and EBV.
A clonal lymphoproliferative disorder that develops following an organ transplantation and is caused by Epstein-Barr virus infection.
An infrequent esophageal carcinoma arising from esophageal glands. (WHO)
A rare morphologic variant of esophageal squamous cell carcinoma. Histologically, it is composed of closely packed cells with hyperchromatic nuclei and scant basophilic cytoplasm. It has a similar prognosis to the conventional squamous cell carcinoma of the esophagus. (WHO)
A rare, well differentiated, low grade tumor with neuroendocrine differentiation that arises from the esophagus. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent. The majority of cases have a polypoid appearance, are small lesions, and found incidentally.
A benign neoplasm arising from the fibrous soft tissue of the esophagus. The tumor is characterized by the presence of spindle-shaped fibroblasts.
A gastrointestinal stromal tumor that arises from the esophagus. The majority are spindle cell tumors that exhibit high mitotic activity and affect the distal esophagus.
A lesion in which the architectural and cytologic abnormalities involve either the lower or both the lower and the upper half of the esophageal glandular epithelium.
A tumor that usually presents with small nodules or small sessile polyps, predominantly in the distal esophagus. Histologically, it is composed of sheets of oval to polygonal cells with a small central nucleus and abundant granular cytoplasm. This is usually a benign tumor. (WHO, 2000) -- 2003
A lesion in which the architectural and cytologic abnormalities involve both the lower and the upper half of the esophageal glandular epithelium.
A lesion in which the architectural and cytologic abnormalities involve both the lower and the upper half of the esophageal mucosa. It includes lesions termed moderate dysplasia, and carcinoma in situ (severe dysplasia). (WHO, 2000) -- 2003
A lesion in which the architectural and cytologic abnormalities involve both the lower and the upper half of the esophageal squamous epithelium.
A very rare Hodgkin lymphoma that arises from the esophagus.
A Kaposi sarcoma arising from the esophagus.
An aggressive malignant smooth muscle neoplasm, arising from the esophagus. It is characterized by a proliferation of neoplastic spindle cells.
A benign adipose tissue neoplasm of the esophagus. Clinical presentation includes obstruction, dysphagia, regurgitation, vomiting and reflux. It may be associated with aspiration and consecutive respiratory infections.
A malignant adipose tissue neoplasm of the esophagus, characterized by multivacuolated lipoblasts with hyperchromatic nuclei, a solid pattern of growth, and a rich vascular network. It arises from the mucosal and submucosal layers of the lower esophagus. Clinical presentation includes progressive dysphagia, nausea, throat discomfort, and foreign body sensation.
A lesion in which the architectural and cytologic abnormalities are confined to the lower half of the esophageal glandular epithelium.
A lesion in which the architectural and cytologic abnormalities are confined to the lower half of the esophageal squamous epithelium.
An extranodal lymphoma that arises from the esophagus with the bulk of the mass located in the esophagus. Dysphagia may be the presenting symptom. The vast majority of cases are diffuse large B-cell lymphomas and B-cell lymphomas of the mucosa-associated lymphoid tissue.
A melanoma affecting the esophageal wall. Melanoma in the esophagus is more commonly metastatic than primary. Primary melanomas of the esophagus are polypoid and clinically aggressive. (WHO, 2000)
A rare carcinoma of the esophagus which contains squamous cells, mucus secreting cells, and cells of an intermediate type. (WHO)
A neoplasm with neuroendocrine differentiation that arises from the esophagus. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A non-metastasizing encapsulated neoplasm arising from nerves in the esophagus. Morphologically, it is characterized by the presence of fibroblasts and Schwann cells.
An extranodal non-Hodgkin lymphoma that arises from the esophagus with the bulk of the mass located in the esophagus. Dysphagia may be the presenting symptom. The vast majority of cases are diffuse large B-cell lymphomas and B-cell lymphomas of the mucosa-associated lymphoid tissue.
A malignant soft tissue neoplasm that arises from the esophagus. Representative examples include Kaposi sarcoma, leiomyosarcoma, rhabdomyosarcoma, and synovial sarcoma.
A rare benign epithelial tumor that is usually asymptomatic but can present with pyrosis and epigastric discomfort with or without dysphagia. Histopathologically, esophageal squamous papilloma has fingerlike projections lined with acanthotic stratified squamous epithelium with conservation of normal cellular with or without cellular atypia.
A lesion in which the architectural and cytologic abnormalities involve either the lower or both the lower and the upper half of the esophageal squamous epithelium.
A rare variant of esophageal squamous cell carcinoma. It is an exophytic, cauliflower-like or papillary mass that can arise in any part of the esophagus. This variant of squamous cell carcinoma grows slowly and invades locally, with a very low metastasizing potential. (WHO)
An adenocarcinoma that arises from the ethmoid sinus. It is classified as intestinal-type or non-intestinal-type adenocarcinoma. Nasal obstruction and epistaxis are the presenting signs.
An adenoid cystic carcinoma that affects the ethmoid sinus.
A benign neoplasm that arises from the ciliated respiratory mucosa that lines the ethmoid sinus. It results from the invagination and proliferation of epithelial cells in the underlying stroma.
An extremely rare meningioma that arises as a primary ectopic tumor in the ethmoid sinus.
A papilloma that arises from the ciliated respiratory mucosa that lines the ethmoid sinus. It is classified as inverted papilloma and oncocytic papilloma.
A squamous cell carcinoma that arises from the mucosal epithelial surface of the ethmoid sinus. Patients may present with nasal fullness, obstruction, and/or epistaxis.
A spectrum of malignant tumors arising from the bone and characterized morphologically by the presence of small round cells. Ewing sarcoma and peripheral primitive neuroectodermal tumor represent the ends of a spectrum, with Ewing sarcoma lacking evidence of neural differentiation and the markers that characterize the peripheral primitive neuroectodermal tumor. Ewing sarcoma and peripheral primitive neuroectodermal tumor may share cytogenetic abnormalities, proto-oncogene expression, cell culture and immunohistochemical abnormalities. Pain and the presence of a mass are the most common clinical symptoms.
A non-neoplastic trophoblastic disorder characterized by the presence of an increased number of implantation-site intermediate trophoblasts infiltrating the endometrium and myometrium extensively. It is associated with pregnancy or abortion.
A benign epithelial neoplasm derived from ceruminous glands in the external auditory canal. It presents as a grey mass covered by skin. It is characterized by a proliferation of glands composed of cells with abundant eosinophilic and granular cytoplasm.
Actinic keratosis that develops in the skin of the external ear.
A basal cell carcinoma that arises from the skin of the external ear.
A carcinoma that arises from the external ear. This category includes squamous cell carcinoma, basal cell carcinoma, and ceruminous adenocarcinoma.
A squamous cell carcinoma that arises from the skin of the external ear.
A benign or malignant sympathetic paraganglioma arising from the retroperitoneum, outside the adrenal gland.
A neuroblastoma arising from an anatomic site other than the brain.
A rare gastrointestinal stromal tumor that presents as a solitary mass outside the gastrointestinal tract.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the extrahepatic bile ducts. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A mucinous cystic neoplasm that arises from the extrahepatic bile ducts.
An embryonal rhabdomyosarcoma that arises from the extrahepatic bile ducts.
A benign neoplasm arising from the extra hepatic bile duct. It is characterized by the presence of spindle-shaped fibroblasts.
A benign smooth muscle neoplasm arising from an extrahepatic bile duct. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from an extrahepatic bile duct. It is characterized by a proliferation of neoplastic spindle cells.
A rare benign adipose tissue neoplasm of the extrahepatic bile duct.
An adenoma that arises from the extrahepatic bile ducts. It is characterized by the presence of a papillary growth pattern.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the extrahepatic bile ducts.
An adenoma that arises from the extrahepatic bile ducts. It is characterized by the presence of a tubular pattern.
An ameloblastoma that arises from the soft tissues in the gingiva or alveolar mucosa. It presents as a painless exophytic mass.
A spectrum of malignant tumors arising from the soft tissues, characterized morphologically by the presence of small round cells. Ewing sarcoma and peripheral primitive neuroectodermal tumor represent the ends of a spectrum, with Ewing sarcoma lacking evidence of neural differentiation and the markers that characterize the peripheral primitive neuroectodermal tumor. Ewing sarcoma and peripheral primitive neuroectodermal tumor may share cytogenetic abnormalities, proto-oncogene expression, cell culture and immunohistochemical abnormalities. Pain and the presence of a mass are the most common clinical symptoms.
A benign or malignant mesenchymal neoplasm with cartilaginous or osseous differentiation arising from the soft tissues exclusively. Representative examples include chondroma, osteoma, and osteosarcoma.
A rare benign overgrowth of bone arising from extraskeletal sites.
Symptoms, physical examination results, and/or laboratory test results related to the organs of special sense.
Lesion affects the lungs, with or without known genital structures invasion.
Lesion invades outside of the uterus, but it is limited to the genital structures.
Gestational trophoblastic tumor in all other metastatic sites.
An adenocarcinoma that arises from the fallopian tube. Histologic subtypes include clear cell, endometrioid, serous, and mucinous adenocarcinoma. It spreads to adjacent organs, regional lymph nodes, and peritoneum.
A rare adenocarcinoma of the fallopian tube composed of malignant glandular epithelium containing clear cells.
An adenocarcinoma that arises from the fallopian tube and resembles the endometrioid adenocarcinoma of the uterus. It usually has a favorable prognosis.
A malignant trophoblastic tumor that arises from the fallopian tube during pregnancy.
A non-neoplastic disorder that affects the fallopian tube. Representative examples include acute and chronic salpingitis, salpingitis isthmica nodosa, and endometriosis.
An adenocarcinoma that arises from the fallopian tube and is characterized by a papillary architectural pattern.
A rare squamous cell carcinoma that arises from the fallopian tube.
A medulloblastoma developing in patients with familiar adenomatous polyposis syndrome. It is observed in patients with Turcot syndrome, type 2.
Cancer aggregating among blood relatives. Does not necessarily imply a genetic inheritance.
A non-neoplastic disorder that affects the female reproductive system. Representative examples include endometriosis, pelvic inflammatory disease, and endometritis.
A precancerous lesion that arises from the female reproductive system. Representative examples include atypical endometrial hyperplasia, endometrial intraepithelial neoplasia, and cervical intraepithelial neoplasia.
A non-neoplastic soft tissue disorder characterized by the localized formation of reactive fibrous and bone tissues. It usually occurs in the subcutaneous tissue of the proximal phalanx. Less frequently, it involves the toe. It presents with swelling and pain of the affected area. The prognosis is excellent. However, incomplete excision may lead to the re-growth of the lesion.
A morphologic finding that indicates the presence of reactive fibrotic stroma in a tissue sample.
A term that refers to the classification of a clinical or laboratory finding according to the anatomic site or system that is involved.
A breast lesion characterized by the presence of dilated terminal ductal lobular units in which the epithelial lining has been replaced by a single layer of mildly atypical cells, or there is atypical, monotonous epithelial hyperplasia of three to five layers. This lesion relates to columnar cell change with atypia and columnar cell hyperplasia with atypia.
A type of hyperplasia that is characterized by a marked thickening of the urinary tract epithelium. There is no evidence of cytologic atypia. -- 2003
A non-neoplastic disorder characterized by the formation of reactive lymphoid follicles adjacent to distal bronchi and bronchioles. It presents with mild shortness of breath and is associated with immunodeficiency syndromes and collagen vascular disorders.
A meningioma that affects the foramen magnum.
A carcinoid tumor that arises from the lung, thymus, esophagus, stomach, or duodenum.
A meningioma that affects the frontal sulcus.
A benign neoplasm that arises from the ciliated respiratory mucosa that lines the frontal sinus. It results from the invagination and proliferation of epithelial cells in the underlying stroma.
A papilloma that arises from the ciliated respiratory mucosa that lines the frontal sinus. It is classified as inverted papilloma and oncocytic papilloma.
A squamous cell carcinoma that arises from the mucosal epithelial surface of the frontal sinus. Patients may present with nasal fullness, obstruction, and/or epistaxis.
A carcinoma that arises from the gallbladder. It is characterized by the presence of glandular and squamous malignant epithelial components.
A malignant vascular neoplasm arising from the gallbladder.
A polypoid tumor that arises from the gallbladder. It is characterized by the presence of elongated, serrated crypts lined by proliferative epithelium.
A Kaposi sarcoma arising from the gallbladder.
A benign smooth muscle neoplasm arising from the gallbladder. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the gallbladder. It is characterized by a proliferation of neoplastic spindle cells.
A benign adipose tissue neoplasm involving the gallbladder wall.
A lymphoma that arises from the gallbladder, with the bulk of the tumor located at this site.
A melanoma that arises from the gallbladder.
An adenocarcinoma that arises from the gallbladder. It is characterized by the presence of extracellular mucin that constitutes more than fifty-percent of the tumor.
A non-metastasizing encapsulated neoplasm arising from nerves in the gallbladder. Morphologically, it is characterized by the presence of fibroblasts and Schwann cells.
An intraluminal papillary neoplasm, usually with high grade intraepithelial neoplasia, that arises from the gallbladder. It is associated with the presence of an invasive carcinoma. The carcinomatous component is usually an adenocarcinoma.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the gallbladder. Intraepithelial neoplasia is present.
A malignant mesenchymal tumor with skeletal muscle differentiation affecting the gallbladder.
A malignant soft tissue neoplasm that arises from the gallbladder. Representative examples include Kaposi sarcoma, leiomyosarcoma, and rhabdomyosarcoma.
An adenocarcinoma that arises from the gallbladder. It is characterized by the presence of signet ring malignant epithelial cells.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the gallbladder. It is characterized by the presence of malignant small cells.
A meningioma that affects the trigeminal ganglion.
A carcinoma that arises from the stomach and is characterized by the presence of malignant cells with glandular and squamous differentiation.
An adenocarcinoma that arises from the gastric cardia. The majority of cases have been reclassified as gastroesophageal junction adenocarcinomas.
A carcinoma that arises from the gastric cardia.
Non-neoplastic polyps that arise from the stomach and are often indistinguishable from hyperplastic polyps. They may be associated with the presence of polyps in other parts of the gastrointestinal tract. Associated clinical signs and symptoms are nail atrophy, alopecia, and hyperpigmentation.
A well differentiated neuroendocrine tumor that arises from the stomach. It produces gastrin and it may be associated with Zollinger-Ellison syndrome.
A gastrointestinal stromal tumor that arises from the stomach. It covers a spectrum of benign to malignant soft tissue neoplasms and includes most gastric smooth muscle tumors, leiomyoblastomas, and tumors formerly called gastrointestinal autonomic nerve tumors.
A benign or malignant germ cell tumor that arises from the stomach. Representative examples include teratoma and choriocarcinoma.
A multinodular intermediate fibroblastic neoplasm arising from the stomach. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells.
A non-neoplastic polyp that arises from the stomach and is characterized by the presence of elongated, tortuous, and cystic foveolar zones, edematous changes, and inflammation. It may be associated with juvenile polyposis in other parts of the gastrointestinal tract.
A Kaposi sarcoma arising from the stomach.
A rare benign adipose tissue neoplasm of the stomach. Clinical presentation includes obstruction and gastrointestinal bleeding. Gastric lipomas occur as solitary lesions most frequently in the antrum.
A malignant adipose tissue neoplasm of the stomach.
A lymphangioma arising from the stomach.
A mantle cell lymphoma that affects the stomach. It may arise as a solitary mass or it may be a component of multifocal lymphomatous polyposis of the gastrointestinal tract. It usually has an aggressive clinical course.
A low grade, indolent B-cell lymphoma, usually associated with Helicobacter pylori infection. Morphologically it is characterized by a dense mucosal atypical lymphocytic (centrocyte-like cell) infiltrate with often prominent lymphoepithelial lesions and plasmacytic differentiation. Approximately 40% of gastric MALT lymphomas carry the t(11;18)(q21;q21). Such cases are resistant to Helicobacter pylori therapy.
A neoplasm with neuroendocrine differentiation that arises from the stomach. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
An extranodal non-Hodgkin lymphoma that arises from the stomach with the bulk of the mass located in the stomach. The vast majority of cases are diffuse large B-cell lymphomas and B-cell lymphomas of the mucosa-associated lymphoid tissue.
A variant of gastric adenocarcinoma with exophytic growth and elongated finger-like processes lined by cylindrical or cuboidal cells supported by fibrovascular connective tissue cores.
A carcinoma that arises from the pylorus.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the stomach. It is characterized by the presence of malignant small cells.
A rare carcinoma of the stomach resembling squamous cell carcinomas arising elsewhere in the body.
A mature or immature teratoma that arises from the stomach.
A variant of gastric adenocarcinoma characterized by prominent dilated or slit-like tubules.
An intestinal-type adenomatous polyp that arises from the stomach. It is characterized by the presence of a tubular architectural pattern.
An intestinal-type adenomatous polyp that arises from the stomach. It is characterized by the presence of a tubulovillous architectural pattern.
An intestinal-type adenomatous polyp that arises from the stomach. It is characterized by the presence of a villous architectural pattern.
A Hodgkin lymphoma that arises from any part of the digestive system, with the bulk of the disease localized to that site.
A melanoma that arises from any part of the digestive system.
A neoplasm with neuroendocrine differentiation arising from the digestive system. It includes neuroendocrine tumors (well-differentiated endocrine tumors or carcinoid tumors and well differentiated endocrine carcinomas) and neuroendocrine carcinomas (poorly differentiated neuroendocrine carcinomas, small cell carcinomas, and large cell neuroendocrine carcinomas).
A non-Hodgkin lymphoma that arises from any part of the digestive system, with the bulk of the disease localized to that site.
A stromal tumor that originates from the interstitial cells of Cajal. It may involve any part of the gastrointestinal tract. The majority of cases occur in the stomach. Morphologic variants include the epithelioid cell type, spindle cell type, and mixed cell type. Most cases contain KIT- or PDGFRA-activating mutations. Lesions with a diameter greater than 10cm and more than 5 mitotic figures per 50HPF tend to have a more aggressive clinical course. Until recently, surgery has been the only effective therapy for this tumor. However, many patients still experience recurrence. A KIT tyrosine kinase inhibitor, imatinib mesylate (also known as STI-571 or Gleevec), is now effective in the treatment of relapsed and unresectable cases.
Symptoms, physical examination results, and/or laboratory test results related to the digestive system.
Infection of the genitalia by human papillomavirus.
Patient complaints (symptoms), physical or laboratory findings (signs) related to the genitourinary system.
A malignant germ cell tumor arising from the central nervous system. It is composed of uniform cells resembling primitive germ cells. These cells have large, vesicular nuclei, prominent nucleoli and a clear, glycogen-rich cytoplasm. Additional features are lymphoid or lymphoplasmacytic infiltrates and, less frequently, scattered syncytiotrophoblastic giant cells. (Adapted from WHO)
A benign, elongated intraluminal polypoid neoplasm of the esophagus. It is characterized by the presence of adipose tissue lobules separated by dense fibrous tissue bands and dilated blood vessels. The polyp is covered by normal squamous epithelium.
A cavernous hemangioma characterized by the presence of hylanized vascular channels and is often associated with the presence of calcifications, fibrosis, and hemorrhage.
A benign neoplasm arising from the fibrous soft tissues of the gingiva. It is characterized by the presence of spindle-shaped fibroblasts and numerous dilated vascular channels.
A variant of malignant peripheral nerve sheath tumor characterized by the presence of glandular epithelium.
A benign multifocal proliferation of glomus cells forming clusters around dilated vascular spaces.
A glomus tumor that shows atypical characteristics and has borderline malignant potential.
A well differentiated invasive breast carcinoma.
A moderately differentiated invasive breast carcinoma.
A poorly differentiated invasive breast carcinoma.
A grade 3 follicular lymphoma in which centrocytes are present.
A grade 3 follicular lymphoma composed of solid sheets of centroblasts.
A colon adenocarcinoma characterized by the presence of a malignant cellular infiltrate with less than 50% glandular formation.
A colorectal adenocarcinoma characterized by the presence of a malignant cellular infiltrate with less than 50% glandular formation.
A rectal adenocarcinoma characterized by the presence of a malignant cellular infiltrate with less than 50% glandular formation.
A colon adenocarcinoma characterized by the presence of a malignant cellular infiltrate with 50-95% glandular formation.
A colorectal adenocarcinoma characterized by the presence of a malignant cellular infiltrate with 50-95% glandular formation.
Penile intraepithelial neoplasia characterized by the proliferation of transformed basaloid cells that occupy the lower two thirds of the epithelial thickness.
High grade prostatic intraepithelial neoplasia characterized by the presence of moderate architectural and cytologic abnormalities.
A rectal adenocarcinoma characterized by the presence of a malignant cellular infiltrate with 50-95% glandular formation.
A colon adenocarcinoma characterized by the presence of a malignant cellular infiltrate with more than 95% glandular formation.
A colorectal adenocarcinoma characterized by the presence of a malignant cellular infiltrate with more than 95% glandular formation.
A pancreatic intraepithelial neoplasia characterized by the presence of tall columnar cells that form flat or papillary, micropapillary, and basally pseudostratified architectural patterns. Mild cytological atypia is present.
A rectal adenocarcinoma characterized by the presence of a malignant cellular infiltrate with more than 95% glandular formation.
An aggressive malignant smooth muscle neoplasm. It is characterized by the presence of malignant smooth muscle cells with granular cytoplasmic changes.
A generally benign intrasellar and/or suprasellar mass arising from the neurohypophysis or infundibulum. It is composed of nests of large cells with granular, eosinophilic cytoplasm due to abundant intracytoplasmic lysosomes. It generally has a slow progression and lacks invasive growth. (Adapted from WHO)
Chronic inflammation of the endometrium characterized by the presence of epithelioid granulomas. Causes include tuberculosis, fungal infections, parasitic infections, and sarcoidosis.
A group of lymphomas displaying molecular, morphologic, immunophenotypic, and clinical overlap between classical Hodgkin lymphoma and diffuse large B-cell lymphoma. This term particularly applies to mediastinal lymphomas with overlapping features of mediastinal (thymic) large B-cell lymphoma and classical Hodgkin lymphoma.
A microscopic finding indicating the presence of nuclei with ground glass appearance due to the presence of intranuclear viral particles that cause peripheral margination of the chromatin.
An adenoid cystic carcinoma arising from the minor salivary glands in the hard palate.
A benign epithelial neoplasm arising from the minor salivary glands in the hard palate. It is characterized by the presence of a monomorphic cellular infiltrate.
A mucoepidermoid carcinoma arising from the minor salivary glands in the hard palate.
A benign, slow-growing and painless neoplasm that arises from the minor salivary glands in the hard palate. It is composed of cells that demonstrate both epithelial and mesenchymal differentiation.
A high-grade, aggressive variant of squamous cell carcinoma that arises from the head and neck region. The most common sites of origin are pyriform sinus, epiglottis, and base of tongue. It is characterized by the presence of small malignant cells with hyperchromatic nuclei and scant amount of cytoplasm forming lobules with peripheral palisading. Comedonecrosis may be present.
A non-neoplastic or neoplastic disorder that affects the anatomic structures of the head and neck region. This category includes inflammatory disorders, benign neoplasms, precancerous conditions, and malignant neoplasms.
A benign or malignant extra-adrenal paraganglioma arising from paraganglia in the head and neck. Representative examples include the carotid body and jugulotympanic paragangliomas.
A premalignant pathologic process that affects the anatomic structures of the head and neck. Representative examples include oral leukoplakia and leukoplakia of the vocal cords.
A rare extramedullary myeloid tumor that arises from the heart. It may present in association with or as a site of relapse of acute myeloid leukemia. Rare cases of myeloid sarcoma of the heart preceding acute myeloid leukemia have also been reported.
An adenocarcinoma that arises from the gastric mucosa and is caused by persistent infection with Helicobacter pylori.
A low grade, indolent B-cell lymphoma that is associated with Helicobacter pylori infection.
A hemangioblastoma arising from structures of the central nervous system.
A hemangioma arising from the peripheral nerves.
A hemangioma arising from the brain and spinal cord.
An angiomyolipoma arising from the liver.
An extremely rare, usually solitary, well-differentiated neuroendocrine tumor (carcinoid tumor) arising from the liver. There is mild nuclear atypia and low mitotic activity present. The neoplastic cells express immunohistochemical evidence of neuroendocrine differentiation. The vast majority of carcinoid tumors found in the liver represent metastases from other anatomic sites.
A premalignant neoplastic nodular lesion of the liver that usually measures less than 15 mm. It is found during microscopic examination of liver tissues, usually in cirrhotic livers. Based on the degree of atypia, it is classified as low or high grade.
A solitary fibrous tumor that arises from the liver. It affects females more frequently than males. Signs and symptoms include the presence of an abdominal mass and abdominal discomfort.
A usually aggressive malignant neoplasm arising from the liver. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
A multinodular intermediate fibroblastic neoplasm arising from the liver. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells.
A benign smooth muscle neoplasm arising from the liver. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the liver. It is characterized by a proliferation of neoplastic spindle cells.
A rare benign adipose tissue neoplasm of the liver.
A multicystic, tumor-like hamartomatous lesion that arises from the liver during fetal development. Clinically, it usually presents as an abdominal mass associated with abdominal distention. Following resection, the prognosis is usually good.
A rare mucosa-associated lymphoid tissue lymphoma that arises from the liver. It is characterized by the presence of centrocyte-like cells surrounding germinal centers. Lymphoepithelial lesions involving the bile duct epithelium may also be present.
A rare non-Hodgkin lymphoma that arises from the liver and the bulk of the tumor is located in the liver. The most frequent types of non-Hodgkin lymphoma that arise from the liver are diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma.
A malignant mesenchymal tumor with skeletal muscle differentiation affecting the liver.
A benign or malignant neoplasm that affects the liver parenchyma or intrahepatic bile ducts. Representative examples of benign neoplasms include hepatocellular adenoma, and bile duct adenoma. Representative examples of malignant neoplasms include hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and lymphoma.
A hepatocellular carcinoma that develops following hepatitis B virus exposure and injury of the liver parenchyma.
A hepatocellular carcinoma that develops following hepatitis C virus exposure and injury of the liver parenchyma.
A hepatocellular carcinoma that develops following hepatitis virus exposure and injury of the liver parenchyma.
A hepatoblastoma composed of cells resembling fetal epithelial cells and small round cells resembling blastema cells.
A hepatoblastoma composed of small cells resembling the fetal hepatocytes, forming thin trabeculae.
An extranodal, mature T-cell non-Hodgkin lymphoma that originates from cytotoxic T-cells, usually of gamma/delta T-cell type. It is characterized by the presence of medium-size neoplastic lymphocytes infiltrating the hepatic sinusoids. A similar infiltrating pattern is also present in the spleen and bone marrow that are usually involved at the time of the diagnosis.
A manifestation of von Hippel-Lindau disease or other familial renal cell cancer syndromes that present as a malignant epithelial neoplasm of the kidney. It is characterized by the presence of lipid-containing clear cells within a vascular network. The tumor usually is bilateral and polycentric, and metastasizes to unusual sites. Late metastasis is common.
Breast carcinoma that has developed in female relatives of patients with history of breast carcinoma.
Breast carcinoma that has developed in male relatives of patients with history of breast carcinoma.
A meningioma that is transmitted from the parents to an offspring.
Ovarian carcinoma that has developed in relatives of patients that have a history of ovarian carcinoma.
An inherited neoplasm arising from paraganglia. The majority of cases (up to 80%) are multifocal.
The protrusion of an organ, or the fascia of an organ, through the wall of the cavity that normally contains it, which results in obstruction, without mention of necrosis of the herniated contents.
A ductal carcinoma in situ characterized by the presence of neoplastic cells with severe dysplasia and the formation of micropapillary, cribriform, or solid patterns. The nuclei show marked pleomorphism and have prominent nucleoli. Mitotic activity is usually present. There is comedo-type of necrosis present in the ducts. The necrotic debris is surrounded by pleomorphic malignant cells.
A finding indicating the presence of Barrett esophagus in which there is marked nuclear pleomorphism and loss of polarity, increased number of atypical mitotic figures, and crypt budding, branching, and crowding.
A gastric intraepithelial lesion characterized by the presence of neoplastic cells that are cuboidal with a high nucleus to cytoplasmic ratio, prominent nucleoli, significant architectural changes, and increased number of mitotic figures.
An aggressive mucoepidermoid carcinoma characterized by the presence of focal necrosis and high mitotic activity. Lymph node and distant metastases are common. The prognosis is usually poor.
A sarcoma with the morphologic features of a high grade tumor and lack of differentiation.
Intraepithelial neoplasia involving the anal canal. The epithelial cells exhibit moderate dysplasia (grade II intraepithelial neoplasia) or severe dysplasia (grade III intraepithelial neoplasia or carcinoma in situ).
Cervical glandular intraepithelial neoplasia characterized by the presence of severe dysplastic changes.
Squamous or glandular cervical intraepithelial neoplasia characterized by the presence of moderate or severe dysplastic changes.
This lesion shows moderate or marked architectural distortion with glandular crowding and prominent cellular atypia. It includes moderate dysplasia and severe dysplasia. (WHO, 2000) -- 2003
A precancerous neoplastic process that affects the squamous, glandular, or transitional cell epithelium without evidence of invasion. According to the degree of nuclear atypia, number of mitotic figures, and presence of architectural distortion, it is classified as grade II (moderate dysplasia) or grade III (severe dysplasia).
An aggressive malignant soft tissue neoplasm that arises from the paranasal sinus. It is characterized by the presence of high-grade histologic features.
Penile intraepithelial neoplasia characterized by the proliferation of transformed basaloid cells that occupy either the lower two thirds of the epithelial thickness (grade II) or the entire thickness of the epithelium (grade III, Bowen atypia, or squamous cell carcinoma in situ).
A carcinoid tumor that arises from the distal colon or rectum.
Rare tumors that affect the hematopoietic and lymphoid tissues. The cells of origin are the histiocytes and accessory cells. They can occur at any age and show no significant variations in geographical distribution. This category includes the histiocytic sarcoma, Langerhans cell histiocytosis, Langerhans cell sarcoma, interdigitading dendritic cell sarcoma/tumor, follicular dendritic cell sarcoma/tumor, and dendritic cell sarcoma, not otherwise specified. (WHO, 2001)
A lymphoproliferative disorder with morphologic features resembling Hodgkin lymphoma that develops in a patient following transplantation.
An Epstein-Barr positive lymphoproliferation fulfilling the criteria for classical Hodgkin lymphoma and arising as a result of post-transplant immunosuppression therapy. It is most often seen in renal transplant patients.
When radioactive material is used to examine the thyroid with a scanner, nodules that collect more radioactive material than the surrounding thyroid tissue are considered ""hot."" Hot nodules are rarely malignant. Hot nodules are sometimes called hyperfunctioning nodules.
An adenocarcinoma strongly associated with human papillomavirus infection.
An anal squamous cell carcinoma related to infection with sexually transmittable human papillomavirus.
A carcinoma that arises from the cervix and is caused by human papillomavirus infection.
A cervical squamous cell carcinoma associated with human papilloma virus infection. Histologic variants include papillary carcinoma, warty carcinoma, and squamotransitional carcinoma.
An endocervical adenocarcinoma that is caused by human papillomavirus infection.
An esophageal squamous cell carcinoma that arises from squamous epithelial cells infected with human papillomavirus.
A squamous cell carcinoma that arises from the penis and is caused by human papillomavirus infection. Morphologic variants include basaloid carcinoma and warty carcinoma.
A squamous cell carcinoma that arises from the vulva and is caused by human papillomavirus infection.
A serious disorder affecting newborns, particularly premature infants. It is caused by deficiency of surfactant, resulting in the formation of a membrane in the alveoli lining. This membrane contains fibrin and cellular debris and interferes with respiration. Infants with this disorder develop breathing problems immediately or in a few hours after delivery. It may lead to respiratory failure.
Replacement of tissue stromal elements by hyaline material.
An abnormal finding in a bone marrow aspirate or biopsy specimen indicating increased cellularity. It can result from hyperplasia of one or more hematopoietic cell lines or malignant neoplasms that affect the bone marrow.
A Kaposi sarcoma that develops after organ transplantation or immunosuppressive treatment.
A malignant teratoma that arises from the stomach.
The presence of an increased number of granulocytic leukocytes, indicating an early-stage response to infection, inflammation, or neoplastic process.
A granulocytic sarcoma composed of myeloblasts and promyelocytes (WHO 2001). --2003
A teratoma that arises from the testis and is composed of immature, fetal type-tissues.
A group of non-neoplastic and neoplastic disorders resulting from the deregulation and/or deficiency of immune system functions. It includes autoimmune disorders (e.g., lupus erythematosus, dermatomyositis, rheumatoid arthritis), congenital and acquired immunodeficiency syndromes including the acquired immune deficiency syndrome (AIDS), and neoplasms (e.g., lymphomas and malignancies secondary to transplantation).
A non-neoplastic or neoplastic disorder that develops in a patient with immunodeficiency. Representative examples include AIDS-related disorders and disorders that develop following organ transplantation.
A non-Hodgkin lymphoma with an indolent clinical course. Representative examples include grade 1 and grade 2 follicular lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma.
A dysfunction in the production of blood cells, resulting in decreased numbers of mature, functioning blood cells of all lines in circulation.
An early post-transplant lymphoproliferative lesion characterized by immunoblastic proliferation and paracortical expansion as seen in infectious mononucleosis. There is architectural preservation of the involved tissues. Oligoclonal or monoclonal cellular populations have been detected in a small number of cases. In some cases, a polymorphic or monomorphic post-transplant lymphoproliferative disorder may follow this early lesion.
An aggressive malignant smooth muscle neoplasm, arising from the inferior vena cava. It is characterized by a proliferation of neoplastic spindle cells.
A carcinoma that arises from the cervix and invades into the stromal tissue.
A morphologic variant of leiomyosarcoma characterized by the presence of an inflammatory infiltrate admixed with malignant spindle cells.
An undifferentiated pleomorphic sarcoma characterized by the presence of numerous inflammatory cells.
A multinodular intermediate fibroblastic neoplasm affecting the central nervous system. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells.
Acute compression of the thoracic cavity, causing increased intrathoracic pressure and the backflow of blood from the right atrium and superior vena cava into the brachiocephalic and jugular veins, with resulting stagnation of blood flow and subsequent localized blood-oxygen desaturation in the head and neck.
Patient complaints (symptoms), physical and/or laboratory findings related to the skin or integument.
Ductal breast carcinoma in situ characterized by the presence of monomorphic neoplastic cells that form cribriform, micropapillary, or solid patterns. Intraluminal necrosis is present in some ducts. Ducts that contain neoplastic cells with occasional nucleoli and coarse chromatin may also be present.
A borderline blood vessel neoplasm that can be locally aggressive, and may metastasize on rare occasions.
Choroid melanoma characterized by the presence of intermediate cells which are similar to but smaller than epithelioid cells.
Ciliary body melanoma characterized by the presence of intermediate cells which are similar to but smaller than epithelioid cells.
Iris melanoma characterized by the presence of intermediate cells which are similar to but smaller than epithelioid cells.
A borderline fibrohistiocytic neoplasm arising from the dermis and extending to the subcutaneous tissues.
A locally aggressive or rarely metastasizing neoplasm that arises from the soft tissues. It is characterized by the presence of neoplastic spindle-shaped fibroblasts.
A fibrohistiocytic neoplasm usually affecting younger patients. It is characterized by an increased risk of local recurrence and a low risk of metastasis.
A lipomatous neoplasm characterized by a high risk of local recurrence and no risk of metastasis.
A morphologic variant of fetal rhabdomyoma characterized by the presence of spindle cell myoblasts and strap-like skeletal muscle cells.
A soft tissue tumor characterized by an increased risk of local recurrence and/or a low risk of metastasis.
A vascular neoplasm with borderline malignant potential.
A rare benign adipose tissue neoplasm of the internal auditory canal, often presenting as an acoustic tumor. It may be intermixed with the vestibulocochlear nerve and may adhere to adjacent structures.
A meningioma that affects the internal auditory canal.
A precancerous neoplastic process that affects the small or large intestine. It is characterized by low or high grade dysplasia of the mucosal epithelium. There is no evidence of invasion.
A finding indicating the replacement of part of the esophageal mucosal epithelium by intestinal-type epithelium.
A neoplasm with neuroendocrine differentiation that arises from the small or large intestine. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A usually indolent, extra-adrenal paraganglioma affecting the intestine. Patients may present with gastrointestinal hemorrhage. Unlike the conventional paragangliomas, this tumor has a peculiar morphologic appearance; it consists of a mixture of epithelioid neuroendocrine cells, Schwann-like cells, and ganglion cell-like elements.
A lymphangioma arising from the organs of the abdominal cavity.
A benign or malignant extra-adrenal paraganglioma arising from the abdominal cavity.
A cystic meningioma that grows within the cerebral hemispheres.
A cavernous hemangioma arising from the brain and meninges.
An extraskeletal myxoid chondrosarcoma arising from the structures within the cranium.
Colloid cysts i.e. cysts filled with gelatinous material, in the central nervous system often are found in the third ventricle. Due to their location, chronic or intermittent hydrocephalus can result. Case reports of sudden death due to acute obstructive hydrocephalus are in the literature. Colloid cysts are benign lesions that should be considered for neurosurgical resection.
A rare benign adipose tissue neoplasm located in the intracranial region. It is a congenital hamartomatous malformation derived from the embryologic meninx primitiva.
A malignant adipose tissue neoplasm of the intracranial region.
A myeloid sarcoma that affects the meninges or the cerebral hemispheres.
A central nervous system embryonal tumor, not otherwise specified arising from the brain.
A benign breast neoplasm characterized by the proliferation of multiple papillomas within the lumen of the ducts.
A ductal carcinoma in situ of the breast characterized by the presence of a cribriform architectural pattern.
An intraductal papillary carcinoma in which the neoplastic epithelial cells are arranged in micropapillary patterns.
A ductal carcinoma in situ of the breast characterized by the presence of sheets of tumor cells without evidence of central necrosis or cell death.
A benign or malignant papillary neoplasm that arises anywhere in the ductal system of the breast. It is characterized by fibrovascular structures lined by epithelial proliferations. This category includes intraductal papilloma and intraductal papillary carcinoma.
A neoplasm that occurs within the spinal canal in the space between the spinal cord and the dura mater. Representative examples include meningioma, neurofibroma, and sarcoma. Signs and symptoms include local and radicular pain, weakness and spinal cord compression.
A mucinous cystic neoplasm that arises from the intrahepatic bile ducts.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the intrahepatic bile ducts.
A benign tumor that is usually solitary, painless, palpable mass that is firm in consistency and slightly movable and often fluctuant. It can occur in any location, but tends to involve the muscles of the thighs, buttocks, and shoulders. On microscopic examination, there is abundant mucoid material and relative hypo cellularity and loose reticulin fibers. Vascular structures are sparse. The cells have a stellate shape with small hyper chromatic pyknotic nuclei and scanty cytoplasm. Some myxomas may show focal areas of hyper cellularity. However absence of nuclear atypia, mitotic figures or necrosis helps to rule out malignancy.
A meningioma that affects the intraorbital structures.
A meningioma that arises from the spinal meninges.
A benign or malignant intrathoracic sympathetic paraganglioma arising from paravertebral paraganglia. In functional tumors, the hypersecretion of catecholamines results in hypertension.
Neoplastic changes in the urinary tract transitional cell epithelium, characterized by cytologic and architectural abnormalities involving part or the entire thickness of the urothelium. It is classified as either low-grade or high-grade. -- 2003
A morphologic variant of angioleiomyoma characterized by the adherence of neoplastic smooth muscle cells to the walls of vascular channels.
A meningioma that affects the ventricles of the brain.
An invasive breast adenocarcinoma with cytological and immunophenotypic characteristics of apocrine differentiation in more than 90 percent of the malignant cells.
A carcinoma that is not confined to the epithelium, and has spread to the surrounding stroma.
An invasive adenocarcinoma of the breast with a favorable clinical outcome, characterized by the presence of a sieve-like or cribriform infiltrating pattern.
An invasive ductal breast carcinoma associated with an invasive lobular carcinomatous component.
An invasive ductal breast carcinoma associated with a lobular carcinomatous component. The lobular carcinomatous component may be in situ or invasive.
A malignant cellular population that has increased in size and infiltrates the surrounding tissues.
A ductal breast carcinoma which invades the breast parenchyma. It is characterized by the formation of papillary structures.
An invasive transitional cell carcinoma that arises from the urinary bladder urothelium.
An endophytic lesion in the urinary tract which shares several morphologic features with urothelial papilloma. This lesion may recur after complete excision. Transitional cell carcinomas may arise within inverted urothelial papillomas.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the jejunum. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A somatostatin-producing neuroendocrine tumor that arises from the jejunum. It is characterized by the presence of tubulo-glandular structures.
A meningioma that affects the jugular foramen.
A neoplasm that affects the jugular foramen. Representative examples include paraganglioma, schwannoma, and meningioma.
A rare intracranial schwannoma that affects the jugular foramen.
A benign, usually solitary, well circumscribed multicystic neoplasm that arises from the breast and typically affects young females. The cysts are lined by papillary proliferations that contain epithelial and myoepithelial layers. In a minority of cases, atypia may be present.
A granulosa cell tumor that affects females in the first three decades of life. In young girls it may present with pseudoprecocity. In women during reproductive years, it may present with menstrual abnormalities.
A rare myxoma that usually arises in an area close to a large joint. Morphologically it resembles a cellular myxoma. In contrast to an intramuscular myxoma, it is not associated with mutations of the GNAS gene.
A Kaposi sarcoma arising from the brain, spinal cord, or meninges.
A squamous cell carcinoma that arises centrally from the jaw. It is characterized by a solid pattern, keratin production, infiltration of the marrow spaces, and osseous resorption.
A carcinoma that arises from the labia majora.
A carcinoma that arises from the labia minora.
A carcinoma that arises from the lacrimal glands. Representative examples include adenocarcinoma, carcinoma ex pleomorphic adenoma, squamous cell carcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma.
An extremely rare carcinoma that arises from the lacrimal gland. It is characterized by the presence of infiltrating nests of epidermoid cells and mucus producing cells.
A high grade malignant neoplasm that arises from the lung and is characterized by the presence of large neuroendocrine cells. It usually has an aggressive clinical course.
An aggressive, non-small cell, poorly differentiated thymic neuroendocrine carcinoma, characterized by the presence of a high mitotic rate and, almost always, necrosis.
A rare adenoid cystic carcinoma of the larynx. It usually arises from the supraglottic or subglottic area. It is characterized by slow progression and late distant metastases.
A rare, well differentiated, low grade neuroendocrine neoplasm that arises from the larynx.
A benign smooth muscle neoplasm arising from the larynx. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the larynx. It is characterized by a proliferation of neoplastic spindle cells.
A rare malignant adipose tissue neoplasm of the larynx. It predominantly affects males. Clinical presentation includes dysphonia, dysphagia and respiratory symptoms. The supraglottis is the most common site of involvement.
A rare mucoepidermoid carcinoma of the larynx. It usually arises from the supraglottic area. Hoarseness and dysphagia are the presenting symptoms.
A benign or malignant neoplasm with neuroendocrine differentiation that arises from the larynx. This category includes paraganglioma, carcinoid tumor, small cell carcinoma, and large cell neuroendocrine carcinoma.
A benign or malignant extra-adrenal parasympathetic paraganglioma arising from paraganglia adjacent to the larynx. Patients may present with hoarseness and dysphagia.
A premalignant pathologic process that affects the epithelial cells of the laryngeal mucosa.
A rare malignant soft tissue neoplasm that arises from the larynx.
A rare carcinoma that arises from the larynx. It is characterized by the presence of small neuroendocrine cells. It metastasizes early and has an aggressive clinical course.
A meningioma that affects the lateral ventricle of the brain.
A benign smooth muscle neoplasm arising from the central nervous system. It is characterized by the presence of intersecting fascicles composed of spindle cells that often lack mitotic activity.
An aggressive malignant smooth muscle neoplasm, arising from the central nervous system. It is characterized by a proliferation of neoplastic spindle cells.
A melanoma that arises from leptomeningeal melanocytes.
A benign hemangiopericytoma with lipomatous differentiation.
A morphologic finding indicating the presence of a cellular infiltrate forming lobules in a tissue sample.
An Ewing sarcoma which is confined to a specific area of the bone and has not spread to other parts of the skeleton.
A small round cell tumor with neural differentiation, confined to a specific site without evidence of spread to another anatomic site.
A pheochromocytoma that does not invade surrounding tissues and is confined to the adrenal glands.
Refers to cancer that has grown beyond the original (primary) tumor to nearby lymph nodes or organs and tissues.
Intraepithelial neoplasia involving the anal canal. The epithelial cells exhibit mild dysplasia (grade I intraepithelial neoplasia).
Ductal breast carcinoma in situ characterized by the presence of small, monomorphic neoplastic cells that form cribriform, micropapillary, or solid patterns. The nuclei are uniform and mitotic figures are rare.
A finding indicating the presence of Barrett esophagus in which the crypts are preserved or mildly distorted. There is nuclear elongation, mild pleomorphism and loss of polarity, mucin depletion, and increased number of mitotic figures.
A gastric intraepithelial lesion characterized by the presence of neoplastic cells with mild cytologic atypia, mild architectural changes, and low number of mitotic figures.
A slow growing mucoepidermoid carcinoma characterized by the presence of keratinization in the neoplastic squamous cells and lumina formation by glandular neoplastic cells. Complete excision may be curative.
Cervical glandular intraepithelial neoplasia characterized by the presence of mild dysplastic changes.
A malignant soft tissue neoplasm that arises from the paranasal sinus. It is characterized by the presence of low-grade histologic features.
Penile intraepithelial neoplasia characterized by the proliferation of transformed basaloid cells that occupy the lower one third of the epithelial thickness.
A meningioma that affects the lower clivus.
A meningioma that arises from the meninges of the lumbar region of the spinal cord.
A benign well-circumscribed tumor, composed of lobules of mature adipocytes, that arises within the lumbosacral tissue of the spine.
A rare usually indolent lung carcinoma characterized by a cribiform and tubular pattern and the presence of glandular epithelial cells. Clinical symptoms include shortness of breath, cough, wheeze, hemopytsis and chest pain.
A carcinoma that has spread to the brain from its original site in the lung, through the hematogenous route.
A carcinoma that originates from the lung and has spread to the liver.
A benign neoplasm arising from the lung. It is characterized by the presence of spindle-shaped fibroblasts.
A lung carcinoma arising from the hilum of the lung.
A benign smooth muscle neoplasm arising from the lung. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the lung. It is characterized by a proliferation of neoplastic spindle cells.
A primary or metastatic meningioma that is present in the lung. The lung is the most frequent site of metastasis of meningiomas.
A benign tumor of the lung composed of mature adipocytes and smooth muscle cells.
A low, intermediate, or high grade malignant neoplasm with neuroendocrine differentiation that arises from the lung. This category includes typical carcinoid tumor, atypical carcinoid tumor, small cell carcinoma, large cell neuroendocrine carcinoma, and combined carcinoma.
A rare non-Hodgkin lymphoma that arises in and is confined to the lung at the time of diagnosis. Representative examples include bronchial mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma.
A benign tumor that arises from the lung. It is characterized by the presence of sclerotic, papillary, solid, and hemorrhagic patterns and hyperplastic type II pneumocytes. Cholesterol clefts, hemosiderin deposition, chronic inflammation, and calcifications may be present. In the majority of cases, it is a solitary and peripheral tumor. Patients are usually asymptomatic.
A Kaposi sarcoma affecting the lymph nodes.
A finding indicating the presence of enlarged lymph nodes and associated polyclonal hypergammaglobulinemia.
A rare carcinoma that arises from the salivary glands, most often the parotid gland. It is characterized by the presence of an undifferentiated carcinomatous component associated with a prominent reactive lymphoplasmacytic infiltrate.
A histologic variant of anaplastic large cell lymphoma characterized by the presence of a large number of histiocytes admixed with the anaplastic lymphoma cells.
An adult T-cell leukemia/lymphoma characterized by generalized lymphadenopathy without peripheral blood involvement. Most patients have advanced disease, however hypercalcemia is not frequently present. -- 2004
A finding referring to the presence of a cellular infiltrate that is composed of lymphocytes and plasma cells in a tissue sample.
A pure fetal or fetal and embryonal epithelial hepatoblastoma characterized by the presence of broad trabeculae.
An adenocarcinoma with serous acinar cell differentiation that arises from the major salivary glands. The vast majority of cases occur in the parotid gland. Patients usually present with a slow growing mass in the parotid area.
An adenocarcinoma that arises from the parotid gland, submandibular gland, or sublingual gland.
An aggressive carcinoma that arises from the major salivary glands. It is characterized by the presence of malignant epithelial and myoepithelial cells forming cribriform, tubular, and solid patterns. It usually presents as a slow growing mass. Patients develop pain because of the tendency of these carcinomas to invade perineural tissues.
A carcinoma that arises from the parotid gland, submandibular gland, or sublingual gland.
A carcinoma that arises from a pleomorphic adenoma in the major salivary glands. It usually originates in the parotid gland. Patients usually present with a history of a long-standing tumor mass which grew rapidly in the past few months. Patients with non-invasive or minimally invasive carcinoma have an excellent prognosis. In cases where there is invasion of the surrounding tissues, the clinical course is aggressive.
A carcinoma that arises from the major salivary glands. It usually arises from the parotid gland. It is the most common primary carcinoma of the salivary glands and usually presents as a firm and painless mass. It is characterized by the presence of epidermoid cells, mucus producing cells, and cells of intermediate type. The majority of cases have a favorable outcome.
A non-Hodgkin lymphoma that arises from the parotid gland, submandibular gland, or sublingual gland. Representative examples include mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma.
A rare malignant soft tissue neoplasm that arises from the parotid gland, submandibular gland, or sublingual gland. Representative examples include fibrosarcoma, angiosarcoma, leiomyosarcoma, and Kaposi sarcoma.
A non-neoplastic disorder that affects the male reproductive system. Representative examples include prostatitis, balanitis, and phimosis.
A premalignant pathologic process arising from an organ of the male reproductive system. It is characterized by cellular atypia and/or dysplasia but does not show morphologic evidence of stromal invasion at the time of diagnosis. Representative examples include prostatic intraepithelial neoplasia, giant condyloma acuminatum of the penis, and penile intraepithelial neoplasia.
A rare, hormonally functioning or non-functioning pituitary gland adenocarcinoma that produces corticotropin. It may be associated with Cushing disease.
A solitary fibrous tumor/hemangiopericytoma, grade 3 that arises from the brain and occurs in the adult population.
A primary or metastatic malignant neoplasm that affects the anterior portion of the tongue.
An extra-adrenal sympathetic paraganglioma of the bladder that metastasizes to other anatomic sites.
An adenomyoepithelioma of the breast in which the epithelial, myoepithelial, or both components have undergone malignant transformation. Such cases may follow an aggressive clinical course, including recurrences and local and distant metastases.
A rare tumor characterized by malignant transformation of an eccrine spiradenoma of the breast.
A rare malignant germ cell tumor that arises within the myocardium or cardiac chambers.
A malignant hemangiopericytoma arising in the heart.
A paraganglioma of the heart that metastasizes to regional or distant anatomic sites.
A very rare malignant peripheral nerve sheath tumor that arises from the heart.
A metastasizing mesenchymal, non-meningothelial neoplasm that arises from the central nervous system.
An uncommon malignant neoplasm that arises from the chest wall bones. Representative examples include chondrosarcoma, osteosarcoma, and Ewing sarcoma/peripheral primitive neuroectodermal tumor.
Malignant neoplasms which occur in the brain, spinal cord, or meninges of children. Brainstem gliomas, medulloblastomas, ependymomas, and certain pineal tumors are relatively common primary malignant tumors of the CNS in children.
A malignant germ cell tumor that occurs during childhood.
Esophageal segments used primarily in pathology, and distinct from the anatomic segments used for clinical purposes.
A malignant germ cell tumor that develops as a primary tumor in an anatomic site other than the testis or ovary.
A malignant non-seminomatous germ cell tumor that develops as a primary tumor in an anatomic site other than the testis or ovary.
A malignant mesenchymal neoplasm with cartilaginous or osseous differentiation arising from the soft tissues exclusively. Extraskeletal osteosarcoma is a representative example.
A malignant germ cell tumor that arises from the stomach. It includes choriocarcinoma and immature teratoma.
A metastasizing granular cell tumor that arises from the stomach.
A metastasizing mesenchymal neoplasm of the stomach. Representative examples include Kaposi sarcoma, leiomyosarcoma, and liposarcoma.
A rare, hormonally functioning or non-functioning pituitary gland adenocarcinoma that produces growth hormone. It may be associated with acromegaly.
A malignant germ cell tumor that affects the structures within the cranium.
An intrathoracic paravertebral paraganglioma that metastasizes to other anatomic sites.
A primary or metastatic malignant tumor involving the leptomeninges.
An extragonadal malignant germ cell tumor that arises from the mediastinum. This category includes seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, mixed germ cell tumors, and immature malignant teratoma.
A malignant hemangiopericytoma arising in the mediastinum.
A malignant neoplasm that arises from the soft tissues of the mediastinum.
A rare variant of malignant peripheral nerve sheath tumor that arises from the mediastinum. It is characterized by the presence of malignant cells that contain melanin.
A malignant soft tissue tumor in which the line of differentiation is uncertain.
A mixed epithelial stromal tumor of the kidney with malignant stromal features.
An aggressive malignant tumor of the female reproductive system, affecting predominantly elderly menopausal women. The endometrium and ovary are the most common sites of tumor origin. Morphologically, it is a high grade tumor, composed of carcinomatous and sarcomatous elements.
A malignant tumor arising from the parotid gland, submandibular gland, or sublingual gland. It includes carcinoma ex pleomorphic adenoma, a malignant epithelial tumor arising from a pre-existing pleomorphic adenoma and carcinosarcoma which is characterized by a mixture of malignant epithelial and sarcomatous elements.
A malignant tumor arising from the minor salivary glands. It includes carcinoma ex pleomorphic adenoma, a malignant epithelial tumor arising from a pre-existing pleomorphic adenoma and carcinosarcoma which is characterized by a mixture of malignant epithelial and sarcomatous elements.
A malignant non-epithelial neoplasm that affects the liver parenchyma and intrahepatic bile ducts. Representative examples include lymphoma, angiosarcoma, and undifferentiated (embryonal) sarcoma.
A thecoma of the ovary that contains lutein cells and may metastasize to other anatomic sites. It is usually characterized by nuclear atypia and mitotic activity.
A malignant neoplasm arising from the ovary. This category includes the poorly differentiated ovarian Sertoli-Leydig cell tumor, malignant ovarian granulosa cell tumor, malignant ovarian steroid cell tumor, and malignant ovarian thecoma.
A malignant tumor arising from the parotid gland. It includes carcinoma ex pleomorphic adenoma, a malignant epithelial tumor arising from a pre-existing pleomorphic adenoma and carcinosarcoma which is characterized by a mixture of malignant epithelial and sarcomatous elements.
A malignant mesenchymal neoplasm arising from the perivascular cells of the connective and soft tissues. It is characterized by the presence of pericytes that grow in a circumferential pattern around vessels, and cytologic atypia.
A malignant germ cell tumor that arises in the pineal region. Representative examples include germinoma, immature teratoma, choriocarcinoma, embryonal carcinoma and yolk sac tumor.
A rare, hormonally functioning or non-functioning pituitary gland adenocarcinoma that produces prolactin.
An unusual malignant tumor that arises from the prostate gland. It is characterized by the presence of glandular elements and a cellular stroma that exhibits mitotic activity and nuclear atypia.
A primary or metastatic malignant neoplasm that affects the male or female reproductive system. Representative examples include prostate carcinoma, penile carcinoma, testicular seminoma, testicular embryonal carcinoma, endometrial carcinoma, cervical carcinoma, ovarian carcinoma, and uterine corpus leiomyosarcoma.
A malignant neoplasm arising from skeletal muscle.
A malignant neoplasm arising from smooth muscle.
A malignant tumor arising from the submandibular gland. It includes carcinoma ex pleomorphic adenoma, a malignant epithelial tumor arising from a pre-existing pleomorphic adenoma and carcinosarcoma which is characterized by a mixture of malignant epithelial and sarcomatous elements.
A classification of testicular cancers that arise in specialized sex cells called germ cells. Nonseminomas include embryonal carcinoma, teratoma, choriocarcinoma, and yolk sac tumor.
A Sertoli cell tumor that arises from the testis and is characterized by nuclear pleomorphism, increased mitotic activity and necrotic changes. Metastases may be present at diagnosis.
A rare, hormonally functioning or non-functioning pituitary gland adenocarcinoma that produces thyrotropin.
A primary malignant neoplasm of the uterine corpus characterized by the presence of an epithelial and a mesenchymal component. This category includes carcinosarcoma, carcinofibroma, and adenosarcoma.
A primary or metastatic malignant neoplasm that affects the choroid, ciliary body, or iris.
A malignant neoplasm arising from the vascular tissue. It is characterized by vascular channel formation and malignant endothelial cells.
A group of non-invasive epithelial proliferations that occur in the ductal system of the breast. The vast majority of cases arise in the terminal ductal lobular units. This category includes atypical ductal hyperplasia, usual ductal hyperplasia, flat epithelial atypia, and ductal carcinoma in situ. There is an increased risk for subsequent development of invasive breast carcinoma.
A neoplasm that arises from mature B-lymphocytes or plasma cells. Representative examples include mature B-cell non-Hodgkin lymphomas, chronic lymphocytic leukemia, hairy cell leukemia, and plasma cell neoplasms.
A non-Hodgkin lymphoma that originates from mature B lymphocytes. Representative examples include diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, mantle cell lymphoma, and small lymphocytic lymphoma.
A benign teratoma that arises from the stomach.
An extragonadal mature teratoma that arises from the mediastinum. It is usually encapsulated and characterized by the presence of unilocular or multilocular cysts. The cysts can contain clear fluid, mucoid material, sebaceous debris, fat, hair, cartilage, and rarely teeth or bone.
An ovarian teratoma which may be cystic, composed entirely of well differentiated, adult-type tissues, without evidence of fetal-type tissues.
A benign teratoma that arises from the pericardium.
A group of neoplasms composed of T-lymphocytes with a mature (peripheral/post-thymic) immunophenotypic profile and/or NK-cells.
A teratoma that arises from the testis and is composed of well differentiated, adult-type tissues.
An adenocarcinoma that arises from the maxillary sinus. It is classified as intestinal-type or non-intestinal-type adenocarcinoma. Nasal obstruction and epistaxis are the presenting signs.
An adenoid cystic carcinoma that arises from the maxillary sinus. It usually has an aggressive clinical course.
A rare, progressive, non-neoplastic pathologic process that arises from the maxillary sinus mucosal epithelium. It is characterized by the proliferation of keratinizing squamous epithelium and the formation of keratin sheets. It may lead to bone erosion and infections. Surgical removal is the appropriate treatment.
A benign neoplasm that arises from the ciliated respiratory mucosa that lines the maxillary sinus. It results from the invagination and proliferation of epithelial cells in the underlying stroma.
A papilloma that arises from the ciliated respiratory mucosa that lines the maxillary sinus. It is classified as inverted papilloma and oncocytic papilloma.
A squamous cell carcinoma that arises from the mucosal epithelial surface of the maxillary sinus. Patients may present with nasal fullness, obstruction, and/or epistaxis.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises in a Meckel diverticulum.
A malignant vascular neoplasm arising from the mediastinum.
A benign neoplasm composed of hyaline cartilage arising from the mediastinum. It is characterized by the presence of chondrocytes, a lobulated growth pattern, and calcification.
An extragonadal malignant germ cell tumor that arises from the mediastinum and is composed of syncytiotrophoblasts, cytotrophoblasts, and intermediate trophoblasts. The prognosis is usually poor.
An extragonadal malignant germ cell tumor that arises from the mediastinum and is composed of primitive large cells with clear or granular cytoplasm forming solid, glandular, or papillary patterns. It usually affects young males. It manifests with respiratory distress, thoracic or shoulder pain, fever, cough, superior vena cava syndrome, or hoarseness.
A ganglioneuroblastoma arising from the mediastinum.
A ganglioneuroma arising from the mediastinum.
A germ cell tumor that arises from the mediastinum. Representative examples include seminoma, embryonal carcinoma, yolk sac tumor, teratoma, and mixed germ cell tumor.
An exceptionally rare, generally benign, granular cell tumor that arises from the mediastinum. All the reported cases were located in the posterior mediastinum.
A mediastinal lymphoma with molecular, morphologic, immunophenotypic, and clinical features of both mediastinal (thymic) large B-cell lymphoma and classical Hodgkin lymphoma. The identification of this group of lymphomas, along with recent gene expression profiling results (PDL2 gene expression in both mediastinal (thymic) large B-cell lymphoma tissues and Hodgkin lymphoma cell lines), further supports the hypothesis that mediastinal (thymic) large B-cell lymphomas and classical Hodgkin lymphomas are related entities.
A Hodgkin lymphoma that arises from the mediastinum. It usually involves mediastinal lymph nodes and/or the thymus. Signs and symptoms include fever, weight loss, fatigue, and night sweats.
A benign smooth muscle neoplasm arising from the mediastium. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the mediastinum. It is characterized by a proliferation of neoplastic spindle cells.
A benign adipose tissue neoplasm of the anterior, middle or posterior mediastinum.
A neoplastic process characterized by a diffuse poorly circumscribed overgrowth of adipose tissue in the mediastinum.
A malignant adipose tissue neoplasm of the anterior, middle or posterior mediastinum.
A lymphangioma arising from the mediastinum.
A lymphoma that arises from the mediastinum. Representative examples include mediastinal (thymic) large B-cell lymphoma and Hodgkin lymphoma.
An extragonadal non-seminomatous malignant germ cell tumor that arises from the mediastinum. This category includes embryonal carcinoma, yolk sac tumor, choriocarcinoma, and mixed germ cell tumors.
A malignant peripheral nerve sheath tumor that arises from the mediastinum. It may be associated with neurofibromatosis. It often spreads to the lungs or pleura.
A melanotic schwannoma that affects the mediastinum.
A benign or malignant soft tissue neoplasm of the mediastinum. Representative examples of benign mediastinal soft tissue neoplasms include chondroma, leiomyoma, lipoma, and rhabdomyoma. Representative examples of malignant mediastinal soft tissue neoplasms include angiosarcoma, leiomyosarcoma, liposarcoma, osteosarcoma, rhabdomyosarcoma, and synovial sarcoma.
An extragonadal non-seminomatous malignant germ cell tumor that arises from the mediastinum and contains teratoma and embryonal carcinoma components.
An extragonadal non-seminomatous malignant germ cell tumor that arises from the mediastinum and is composed of two or more germ cell tumor types. It manifests with respiratory distress, thoracic pain, cough, superior vena cava syndrome, or hoarseness.
A neurogenic tumor that arises from the mediastinum. Neural tumors are the most common tumors that arise from the posterior mediastinum. Representative examples include Schwannoma, neurofibroma, and neuroblastoma.
A neuroblastoma arising from the mediastinum.
A neurofibroma that arises from the posterior mediastinum. Excision is usually curative.
An osteosarcoma arising from the mediastinum.
A rare benign skeletal muscle neoplasm arising from the mediastinum.
A malignant mesenchymal tumor with skeletal muscle differentiation affecting the mediastinum.
A rare sarcoma that arises from the mediastinum. Examples include liposarcoma, leiomyosarcoma, and angiosarcoma.
A schwannoma that arises from the posterior mediastinum. It is the most common neurogenic tumor of the mediastinum. Excision is usually curative.
An extragonadal malignant germ cell tumor that arises from the mediastinum. It is characterized by the presence of uniform cells with clear or eosinophilic cytoplasm, round nucleus with one or more nucleoli, and distinct cellular borders. It usually arises from the anterior mediastinum. It may present with respiratory distress, chest pain, or superior vena cava syndrome or it may be asymptomatic, with the tumor detected on routine chest x-ray. The prognosis of mediastinal pure seminomas is favorable compared to the mediastinal non-seminomatous malignant germ cell tumors.
A synovial sarcoma arising from the mediastinum.
A teratoma located with the mediastinum (the cavity between the pleural sacs that contains the heart and all of the thoracic viscera except the lungs).
An extragonadal non-seminomatous malignant germ cell tumor that arises from the mediastinum. It is characterized by the presence of small pale cells with small amount of cytoplasm and round to oval nuclei with small nucleoli forming a variety of patterns, including microcystic, macrocystic, pseudopapillary, myxomatous, hepatoid, polyvesicular vitelline, and solid. It manifests with respiratory distress, thoracic pain, fever, and superior vena cava syndrome.
A medulloblastoma which has spread from its original site to the leptomeninges surrounding the brain and spinal cord.
A neoplasm that arises from meningothelial cells. This category refers to meningiomas.
A benign, intermediate, or malignant neoplasm that arises from the mesenchyma-derived cells of the soft tissue or bone. Representative examples include lipoma, leiomyoma, leiomyosarcoma and osteosarcoma.
A malignant tumor that arises at a site separate from another, primary malignant tumor in the same anatomic system. It is not clear if metachronous malignant neoplasms represent new primary tumors or metastatic disease. Examples include metachronous osteosarcoma of the bones that develops in patients with known primary bone osteosarcoma, and metachronous Wilms' tumor that affects the opposite kidney in patients with a history of Wilms' tumor.
A bone osteosarcoma that has metastasized to skeletal or extraskeletal sites.
Wilms tumor arising in the remaining kidney following treatment of the original Wilms tumor.
A group of invasive breast carcinomas characterized by the presence of an adenocarcinomatous component which is admixed with a dominant component that is composed of squamous cells, spindle cells, or mesenchymal cells.
A very rare pleomorphic adenoma of the salivary glands that metastasizes inexplicably, despite the benign histopathologic features. The most common sites of metastasis are bone, lung, and head and neck.
An Ewing sarcoma of the bone which has spread from its original site of growth to another anatomic site.
A carcinoid tumor that arises from the breast and has metastasized to other anatomic sites.
A carcinoid tumor that has extended beyond its original site of growth to other anatomic sites.
A carcinoma that has spread to the adrenal cortex from an adjacent or distal anatomic site.
A carcinoma that has spread to the adrenal medulla from an adjacent or distant anatomic site.
A small round cell tumor with or without neural differentiation which has spread from its original site of growth to another anatomic site.
A jugulotympanic paraganglioma that has metastasized to other anatomic sites.
The presence of malignant Schwann cell growth (benign variant is known as neurofibroma) at a site removed from the primary site of tumor growth.
A meningioma that has spread from its original site of growth to another anatomic site.
A malignant neoplasm that has spread from its original site of growth to the brain in an adult patient.
A malignant neoplasm that has spread to the nasopharynx from another anatomic site.
A primary small cell carcinoma of the ovary that is associated with hypercalcemia and has metastasized to other anatomic sites.
A signet ring cell carcinoma that arises from the breast and has metastasized to other anatomic sites.
A squamous cell carcinoma that arises from the breast parenchyma and has metastasized to other anatomic sites.
A lymphoproliferative disorder that develops in patients who are immunosuppressed with methotrexate. This disorder is often Epstein-Barr virus positive, and morphologically it may resemble large B-cell non-Hodgkin lymphoma, Hodgkin lymphoma, or a polymorphous post-transplant lymphoproliferative disorder. (WHO, 2001)
A rare variant of breast adenosis characterized by the proliferation of small round glands in a collagenous stroma. The epithelial cells are cuboidal and there are no myopepithelial cells present. There is no evidence of atypia.
A morphologic finding indicating the presence of an architectural pattern dominated by the presence of small papillary structures.
A meningioma that affects the middle cranial fossa.
A rare adenocarcinoma that arises from the middle ear.
A benign, well-circumscribed glandular neoplasm that arises from the middle ear and may exhibit neuroendocrine differentiation. It usually presents with conductive hearing loss.
A carcinoma that arises from the middle ear. This category includes adenocarcinoma and squamous cell carcinoma.
A benign or malignant jugulotympanic paraganglioma arising from paraganglia in the middle ear.
A rare squamous cell carcinoma that arises from the middle ear.
A carcinoid tumor that arises from the jejunum, ileum, proximal colon, or appendix.
An adenocarcinoma with serous acinar cell differentiation that arises from the minor salivary glands.
An adenocarcinoma that arises from the minor salivary glands.
An aggressive carcinoma that arises from the minor salivary glands. It is characterized by the presence of malignant epithelial and myoepithelial cells forming cribriform, tubular, and solid patterns. It usually presents as a slow growing mass.
An infrequent small cell carcinoma that arises from a minor salivary gland and is characterized by the presence of a high number of mitotic figures.
A carcinoma that arises from the minor salivary glands. Representative examples include adenoid cystic carcinoma, acinic cell carcinoma, polymorphous low grade adenocarcinoma, and mucinous adenocarcinoma.
A carcinoma that arises from a pleomorphic adenoma in the minor salivary glands. Patients usually present with a history of a long-standing tumor mass which grew rapidly in the past few months. Patients with non-invasive or minimally invasive carcinoma have an excellent prognosis. In cases where there is invasion of the surrounding tissues, the clinical course is aggressive.
A carcinoma that arises from the minor salivary glands. It usually presents as a firm and painless mass. It is characterized by the presence of epidermoid cells, mucus producing cells, and cells of intermediate type. The majority of cases have a favorable outcome.
A squamous cell carcinoma that affects the minor salivary glands.
A carcinoma that affects the minor salivary glands and is characterized by the presence of undifferentiated, anaplastic malignant epithelial cells.
A benign,intermediate, or malignant soft tissue tumor in which the line of differentiation is uncertain. Representative examples include neoplasm with perivascular epithelioid cell differentiation, alveolar soft part sarcoma, desmoplastic small round cell tumor, epithelioid sarcoma, extraskeletal myxoid chondrosarcoma, and synovial sarcoma.
Having to do with the presence of dividing (proliferating) cells. Cancerous tissue generally has more mitotic activity than normal tissues.
A gastrointestinal stromal tumor composed of a mixture of neoplastic epithelioid and spindle cells.
A melanoma arising from the choroid, ciliary body, or the iris. It is characterized by the presence of a mixture of spindle A melanoma cells, spindle B melanoma cells, and epithelioid melanoma cells.
A malignant germ cell tumor arising from the testis. It is characterized by a mixture of embryonal carcinoma, yolk sac, and seminomatous morphologic elements. Patients may present with painless or painful testicular swelling.
A hepatoblastoma characterized by the presence of fetal and embryonal epithelial components and a mesenchymal component.
A malignant germ cell tumor of the central nervous system characterized by the presence of at least two types of germ cell neoplasia.
A hepatoblastoma characterized by the presence of mixed epithelial and mesenchymal components and additional tissues such as striated muscle, bone, epithelial tissues, and melanin pigment.
A lung carcinoma characterized by a combination of small cell carcinoma and squamous cell carcinoma.
An invasive prostate adenocarcinoma characterized by the presence of malignant cells exhibiting moderate differentiation.
A less common form of myeloid sarcoma composed of monoblasts. Monoblastic sarcoma may precede or occur simultaneously with acute monoblastic leukemia. (WHO 2001)
A clonal B-cell lymphoproliferative disorder arising as a result of post-transplant immunosuppression therapy. It is characterized by destructive infiltration of lymph nodes and extranodal sites by a monotonous population of transformed B-lymphocytes or plasma cells. The clonal cellular infiltrates fulfill the criteria for a diffuse large B-cell lymphoma, Burkitt lymphoma, or a plasma cell neoplasm.
A clonal lymphoproliferative disorder arising as a result of post-transplant immunosuppression therapy. It is characterized by destructive infiltration of lymph nodes and extranodal sites by a monotonous population of transformed lymphocytes or plasma cells. It includes two variants: monomorphic B-cell and monomorphic T/NK cell post-transplant lymphoproliferative disorders.
A clonal T-cell lymphoproliferative disorder arising as a result of post-transplant immunosuppression therapy. It is characterized by destructive infiltration of lymph nodes and extranodal sites by a monotonous population of transformed T-lymphocytes/NK-cells. The clonal cellular infiltrates fulfill the criteria for any of the T-cell or natural killer cell lymphomas.
A synovial sarcoma characterized by the presence of an epithelial or a spindle cell component only.
A microscopic finding that relates to the architectural patterns of a normal or abnormal cellular population in a tissue specimen.
A morphologic finding indicating the replacement of part of the glandular endometrial epithelium by nodular structures that contain non-keratinizing squamous cells.
The presence of an alteration in the ability to move one's body or any body parts in accordance with one's intent.
An invasive adenocarcinoma of the breast characterized by the presence of islands of small and uniform cells, surrounded by large amounts of mucin. Pure mucinous breast carcinomas generally have a favorable prognosis.
A variant of gastric adenocarcinoma with more than half of the tumor containing extracellular mucinous pools.
A carcinoma of the breast characterized by pools of mucin and islands of malignant squamous cells. Mucoepidermoid carcinomas of the breast are extremely rare.
A rare primary thymic carcinoma, characterized by the presence of squamous cells, intermediate type cells, and mucus-producing cells. The prognosis depends on histologic grade and stage.
A form of angiofollicular lymphoid hyperplasia characterized by fever, generalized lymphadenopathy, hypergammaglobulinemia, and dysfunction of multiple organs. Other signs and symptoms include anemia, thrombocytopenia, hepatomegaly, peripheral neuropathy and pleural effusions. Morphologically, in the majority of cases the lymph nodes show features of angiofollicular lymphoid hyperplasia of the plasma cell type. In a minority of cases, changes of angiofollicular lymphoid hyperplasia of the hyaline-vascular type are seen. In contrast to patients with localized disease who are usually cured following resection of the lesion, patients with the multicentric form of the disease may follow a progressive clinical course, complicated by infection, Kaposi sarcoma, or lymphoma.
A papillary carcinoma arising from the thyroid gland from multiple foci.
A cystic mesothelioma that arises from the peritoneum and usually affects young to middle aged females. Grossly, it presents as a large multiloculated tumor mass, usually in the pelvic peritoneum. Histologically it is characterized by the presence of multiple cysts that are lined by one or more layers of mesothelial cells that do not show atypia. Patients usually present with abdominal or pelvic mass and pain. The clinical course is indolent. The tumor may recur, but transformation to diffuse malignant mesothelioma is rare.
A lesion arising from or having many locations.
A primary bone osteosarcoma affecting multiple bone sites.
The presence of multiple hamartomas in the lungs. Hamartomas are usually solitary lesions on chest-x-rays. Multiple lung hamartomas are rare.
Multiple meningiomas that arises from the spinal meninges.
A lobular hemangioma present in multiple anatomical sites.
Multiple painful, dome-shaped, translucent pink to skin-colored papules on oral mucosa. Histologically, the lesions may demonstrate dermal proliferation of well-demarcated nerve bundles associated with abundant mucin and surrounded by a distinct perineural sheath.
Multiple meningiomas that affect the skull base.
A morphologic variant of fetal rhabdomyoma characterized by the presence of a prominent myxoid stroma and primitive skeletal spindle cells.
A morphologic finding that indicates the presence of myxoid changes in the stroma of a tissue sample.
An adenocarcinoma that arises from the nasal cavity. It is classified as intestinal-type or non-intestinal-type adenocarcinoma. Nasal obstruction and epistaxis are the presenting symptoms.
A primary lymphoma that affects the nasal cavity and the bulk of the tumor is in this anatomic area.
A primary non-Hodgkin lymphoma that affects the nasal cavity and the bulk of the tumor is in this anatomic area. The majority of the cases are nasal type extranodal NK/T-cell lymphomas and diffuse large B-cell lymphomas.
An olfactory neuroblastoma arising in the nasal cavity.
A non-neoplastic or neoplastic disorder that affects the nasal cavity or paranasal sinuses. Representative examples include inflammatory disorders, papillomas, and carcinomas.
A benign or malignant neoplasm that affects the nasal cavity or paranasal sinuses. Representative examples of benign neoplasms include Schneiderian papilloma and salivary gland-type adenoma. Representative examples of malignant neoplasms include carcinoma and lymphoma.
A nasopharyngeal carcinoma characterized by the lack of keratinization and the presence of a dense lymphoplasmacytic infiltrate. It is subdivided into undifferentiated and differentiated types, based on the cytologic features of the malignant cells. The undifferentiated type is characterized by the presence of cells with large vesicular nuclei with prominent nucleoli and a syncytial pattern of growth. The differentiated type is characterized by the presence of smaller cells and cellular stratification reminiscent of transitional cell carcinoma. While morphologically distinct, both types have similar clinical presentation and prognosis.
A carcinoma that arises from the anatomic structures of the neck region.
A finding indicating the presence of cellular necrosis in a tissue specimen.
A uveal melanoma characterized by the presence of tumor cell necrosis.
A test result that indicates that a specific disease, condition, or attribute being assessed is not present.
A neoplasm defined by its unique characteristic as they apply to clinical presentation and course, morphologic patterns, frequency, and/or age distribution.
A lymphoproliferative disorder arising as a result of post-transplant immunosuppression therapy. It is characterized by the presence of tissue destruction and effacement of the architecture of the involved tissues. There is clonal rearrangement of the immunoglobulin or the T-cell receptor genes. It includes the following variants: polymorphic, monomorphic, and classical Hodgkin lymphoma type post-transplant lymphoproliferative disorders.
Benign and malignant neoplasms arising from one or more of the cervical, thoracic, lumbar, sacral, or coccygeal nerve roots. The majority of these tumors are benign. Clinical manifestations may include pain, weakness and loss of sensation along the course of the involved nerve root. Large tumors may cause spinal cord compression.
A microscopic finding indicating that the neoplastic cells are arranged in compact nests in a tumor sample.
A group of nervous system tumors which display neuronal differentiation. It includes tumors that are composed of immature round cells and tumors that display advanced differentiation and the formation of ganglion cells.
A common pediatric extracranial tumor arising from neural crest cells. It involves the adrenal medulla and the sympathetic nervous system.
A morphologic category that includes neoplasms arising from cells that form and support the nervous system. Such neoplasms include neuroepithelial cell neoplasms and neoplasms that arise from the perineural sheaths (perineurial cell neoplasms and Schwann cell neoplasms). --2003
A low-grade neoplasm that arises from the neurohypophysis. It includes the granular cell tumor of the neurohypophysis and pituicytoma.
A morphologic finding referring to an acute inflammatory infiltrate that is composed of polymorphonuclear cells.
A medulloblastoma developing in patients with multiple basal cell carcinomas. It is observed in patients with nevoid basal cell carcinoma syndrome and it is associated with PTCH gene inactivation.
A carcinoma that arises in the area of the nipple. Representative examples include Paget disease and skin squamous cell carcinoma.
A carcinoma that develops in the ducts of the nipple.
A monoclonal B-cell neoplasm characterized by a nodular, or a nodular and diffuse proliferation of scattered large neoplastic cells known as popcorn or lymphocyte predominant cells (LP cells)- formerly called L&H cells for lymphocytic and/or histiocytic Reed-Sternberg cell variants. The LP cells lack CD15 and CD30 in nearly all instances. Patients are predominantly male, frequently in the 30-50 year age group. Most patients present with limited stage disease (localized peripheral lymphadenopathy, stage I or II). (WHO 2008)
A reactive lymphoid proliferation manifesting as solitary or multiple nodules in the lung.
A medulloblastoma characterized by nodularity and neuronal differentiation.
A benign or malignant neoplasm characterized by the formation of nodules by the proliferating neoplastic cells.
A morphologic architectural pattern characterized by the presence of proliferating non-neoplastic or neoplastic cells forming single or multiple nodules within a lesion.
Melanoma is a malignant tumor of melanocytes, cells that are derived from the neural crest. Although most melanomas arise in the skin, they also may arise from mucosal surfaces or at other sites to which neural crest cells migrate. (PDQ)
A benign or malignant non-epithelial neoplasm that affects the liver parenchyma and intrahepatic bile ducts. Representative examples of benign non-epithelial neoplasms include hemangioma, angiomyolipoma, and solitary fibrous tumor. Representative examples of malignant non-epithelial neoplasms include lymphoma, angiosarcoma, and undifferentiated (embryonal) sarcoma.
A low or intermediate grade well differentiated tumor with neuroendocrine differentiation that arises from the pancreas. It is characterized by the absence of a hormone-related clinical syndrome.
The most common type of renal cell carcinoma, characterized by a loss of genetic material of the short arm of chromosome 3. The most common symptom at the time of diagnosis is hematuria. The tumor has a golden-yellow color because of the abundance of intracytoplasmic lipid. This is a clinically aggressive type of renal cell carcinoma. The tumor usually metastasizes to unusual sites and late metastasis is common.
A neoplastic process that is confined to the site of origin without morphologic evidence of cellular infiltration of the surrounding tissues.
A squamous cell carcinoma that arises centrally from the jaw. It is characterized by a solid pattern, lack of prominent keratinization, infiltration of the marrow spaces, and osseous resorption.
A neoplasm for which no exact measurement may be obtained. This may be due to a size below detection, an invasive presentation, or pertain to an effusion or ascites.
A lesion characterized by the absence of clinical and/or morphologic criteria that are suggestive of melanoma.
A non-neoplastic disorder that affects the structures of the axilla. Representative examples include axillary lymphadenitis and axillary abscess.
A non-neoplastic disorder that affects the urinary bladder. Representative examples include cystitis, cystolithiasis, and urinary bladder rupture.
A non-neoplastic disorder that affects the bone or articular cartilage.
A non-neoplastic disorder that affects the breast. Representative examples include fibrocystic disease, gynecomastia, mastitis, and adenosis.
A non-neoplastic disorder that affects the heart and/or vessels. Representative examples include myocardial infarction, endocarditis, arteriosclerosis, thrombosis, and lymphedema.
A non-neoplastic disorder that affects the structures of the chest wall.
A non-neoplastic disorder that affects the connective and soft tissue.
A non-neoplastic disorder that affects the teeth and/or the periodontal tissues. Representative examples include odontoma, enamel hypoplasia, and periodontitis.
A non-neoplastic disorder that affects the ear. Representative examples include infection, cholesteatoma, and hearing disorders.
A non-neoplastic disorder that affects the endocrine system. Representative examples include diabetes mellitus, hyperthyroidism, and adrenal gland insufficiency.
A non-neoplastic disorder that affects the pinna and/or the ear canal.
A non-neoplastic disorder that affects the gastrointestinal tract, anus, liver, biliary system, and pancreas. Representative examples include infections, ulcers, cirrhosis, and diverticulosis.
A non-neoplastic disorder that affects the testis or the ovary. Representative examples include gonadal agenesis, dysgenesis, and hypogonadism.
A non-neoplastic disorder that affects the hair. Representative examples may include alopecia, male pattern baldness, hirsutism, and hair shaft disorders.
A non-neoplastic disorder that affects the anatomic structures of the head and neck region.
A non-neoplastic disorder that affects the heart and/or the pericardium. Representative examples include congestive heart disease, endocarditis, and constrictive pericarditis.
A non-neoplastic disorder that affects the inner ear. Representative examples include infection and sensory hearing loss.
A non-neoplastic pathologic process that affects the larynx. Representative examples include laryngitis, vocal cord nodule, and laryngeal cleft.
A lung disorder not caused by a neoplasm. Representative examples include chronic obstructive pulmonary disease, atelectasis, lung infections, pulmonary fibrosis, and pneumoconiosis.
A non-neoplastic disorder that affects the structures of the mediastinum. Representative examples include mediastinitis and thymic hyperplasia.
A non-neoplastic disorder that affects the nasal cavity. Representative examples include rhinitis and Wegener granulomatosis.
A non-neoplastic disorder that affects the nasal cavity or paranasal sinuses. Representative examples include rhinitis, sinusitis, and mucocele.
A non-neoplastic disorder that affects the anatomic structures of the neck region. This category includes non-neoplastic disorders of the pharynx, larynx, thyroid gland, and parathyroid gland.
A non-neoplastic disorder that affects the oral cavity. Representative examples include inflammation, fibroepithelial polyp, and cleft palate.
A non-neoplastic disorder that affects the oral cavity or the lips.
A non-neoplastic disorder that affects the paranasal sinuses. Representative examples include sinusitis and mucocele.
A non-neoplastic disorder that affects the parathyroid glands. Representative examples include hyperparathyroidism and hypoparathyroidism.
A non-neoplastic disorder that affects the peritoneal cavity. Representative examples include peritonitis and panniculitis.
A non-neoplastic disorder that affects the pharynx. Representative examples include pharyngitis and mucositis.
A non-neoplastic disorder that affects the pituitary gland. Representative examples include pituitary gland hypoplasia and apoplexy.
A non-neoplastic disorder that affects the pleura. Representative examples include pleural infection and pneumothorax.
A lymphoproliferative disorder arising as a result of post-transplant immunosuppression therapy. It is characterized by the lack of tissue destruction and the architectural preservation of the involved tissues. It includes two morphologic variants: plasmacytic hyperplasia and infectious mononucleosis-like lymphoproliferative disorders.
A non-neoplastic disorder that affects the renal parenchyma and/or renal pelvis. Representative examples include glomerulonephritis and pyelonephritis.
A non-neoplastic disorder that affects the male or female reproductive system. Representative examples include prostatitis, balanitis, phimosis, endometriosis, and pelvic inflammatory disease.
A non-neoplastic disorder that affects the respiratory system. Representative examples include pneumonia, chronic obstructive pulmonary disease, pulmonary failure, tracheitis, and tracheal agenesis.
A non-neoplastic disorder that affects the major or minor salivary glands.
A non-neoplastic disorder that affects the soft tissue.
A non-neoplastic disorder that affects the sternum.
A non-neoplastic disorder that affects the thorax and/or the organs of the thoracic cavity. Representative examples include pleural infection, mediastinitis, pneumonia, and chronic obstructive pulmonary disease.
A non-neoplastic disorder that affects the thymus. Representative examples include acute thymic involution and thymic hyperplasia.
A non-neoplastic disorder that affects the thyroid gland. Representative examples include hyperthyroidism, hypothyroidism, thyroiditis, and thyroid gland abscess.
A non-neoplastic disorder that affects the trachea. Representative examples include tracheitis, tracheal agenesis, and tracheal atresia.
A non-neoplastic disorder affecting the ureter.
A non-neoplastic disorder affecting the urethra.
A non-neoplastic disorder that affects the urinary system. Representative examples include urinary tract infections, urolithiasis, and acute kidney insufficiency.
A group of testicular cancers that begin in the germ cells (cells that give rise to sperm). Nonseminomas are identified by the type of cell in which they begin and include embryonal carcinoma, teratoma, choriocarcinoma, and yolk sac carcinoma.
A carcinoma characterized by the presence of large adenocarcinoma cells.
Chronic endometritis characterized by the presence of plasmacytic infiltrates in the endometrium. There are no granulomas present.
Wilms tumor of the kidney characterized by the absence of nuclear anaplasia.
A rare soft tissue tumor of uncertain lineage characterized by the presence of neoplastic spindle to round cells forming cords in a fibromyxoid stroma. Metaplastic bone formation is not present.
A bone tumor arising from the remnants of the fetal notochord. This category includes the chordoma and benign notochordal cell tumor.
An adenosquamous lung carcinoma detectable by sputum cytology only. The primary tumor is undetectable radiographically or during bronchoscopy; therefore, it can not be assessed.
A large cell lung carcinoma detectable by sputum cytology only. The primary tumor is undetectable radiographically or during bronchoscopy; therefore, it can not be assessed.
A lung adenocarcinoma detectable by sputum cytology only. The primary tumor is undetectable radiographically or during bronchoscopy; therefore, it can not be assessed.
A lung carcinoma detectable by sputum cytology or bronchial washings only. The primary tumor is undetectable radiographically or during bronchoscopy; therefore, it can not be assessed.
A non-small cell lung carcinoma detectable by sputum cytology only. The primary tumor is undetectable radiographically or during bronchoscopy; therefore, it can not be assessed.
A small cell lung carcinoma detectable by sputum cytology only. The primary tumor is undetectable radiographically or during bronchoscopy; therefore, it can not be assessed.
A squamous cell lung carcinoma detectable by sputum cytology only. The primary tumor is undetectable radiographically or during bronchoscopy; therefore, it can not be assessed.
Malignant neoplasm secondary to occupational exposure to carcinogens.
An extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue that arises from the ocular adnexa. It is the most common type of primary ocular adnexal lymphoma.
A meningioma that affects the olfactory sulcus.
A neoplasm of the central nervous system composed predominantly of cells morphologically resembling oligodendroglia. Oligodendroglial tumors histologically comprise a continuous spectrum ranging from well-differentiated neoplasms to frankly malignant tumors. WHO grading system recognizes two malignancy grades: WHO grade II for well-differentiated tumors (oligodendroglioma) and WHO grade III for anaplastic oligodendroglioma. (Adapted from WHO)
A cholangiocarcinoma that has developed following infection with Opisthorchis viverrini.
An adenocarcinoma that arises from the oral cavity.
A monomorphic or pleomorphic adenoma that arises from the salivary glands in the oral cavity.
A rare benign neoplasm that arises from the oral cavity, usually the tongue. It is characterized by the presence of plump eosinophilic cells with abundant granular cytoplasm. The neoplastic cells extend into the surrounding tissues, usually skeletal muscle. Recurrences are rare after removal of the tumor.
A rare neoplasm that arises from the oral cavity, usually the tongue. It is characterized by the presence of plump eosinophilic cells with abundant granular cytoplasm. The neoplastic cells extend into the surrounding tissues, usually skeletal muscle. The vast majority of cases follow a benign clinical course. Recurrences are rare after removal of the tumor.
A benign smooth muscle neoplasm arising from the oral cavity. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A benign adipose tissue neoplasm of the oral cavity. It usually occurs within the lingual and buccal mucosa.
A benign epithelial neoplasm arising from the salivary glands in the oral cavity. It is characterized by the presence of a monomorphic cellular infiltrate.
A rare melanoma that arises from the oral cavity. It is associated with a poor prognosis.
A benign, slow-growing and painless neoplasm that arises from the salivary glands in the oral cavity. It is composed of cells that demonstrate both epithelial and mesenchymal differentiation.
A malignant soft tissue neoplasm that arises from the oral cavity. Representative examples include Kaposi sarcoma and angiosarcoma.
A premalignant pathologic process that affects the mucosa surface of the oral cavity or lip. It includes leukoplakia, erythroplakia, and smoker's keratosis.
A malignant mesenchymal neoplasm that arises in the orbit. It is characterized by the presence of round cells with myoblastic differentiation and a fibrovascular stroma.
A malignant mesenchymal neoplasm that arises from the orbit. It is characterized by the presence of skeletal muscle tissue exhibiting embryonic features.
A benign or malignant extra-adrenal paraganglioma arising from the orbit. Patients may present with visual disturbances or proptosis.
A malignant soft tissue neoplasm that arises from the structures of the orbit. The majority of the cases are rhabdomyosarcomas.
A rare adenoid cystic carcinoma that arises from the oropharynx.
A benign exophytic growth that arises from the oropharynx.
A benign exophytic neoplasm that arises from the oropharynx. It is characterized by the presence of a connective tissue core covered by stratified squamous epithelium [NCI thesaurus].
A benign, intermediate, or malignant bone-forming neoplasm. Representative examples include osteoma, osteoblastoma, and osteosarcoma.
A sarcomatous transformation of pre-existing Paget disease of the bone. Osteosarcomas arising from Paget disease of the bone are high grade lesions and usually have a poor prognosis.
An osteosarcoma arising from the breast tissue.
An osteosarcoma arising from the brain or spinal cord.
A malignant vascular neoplasm arising from the ovary.
A well differentiated neuroendocrine neoplasm that arises from the ovary. Histologically, it is classified as insular, trabecular, mucinous, or stromal carcinoid. Clinical manifestations of carcinoid syndrome occur in approximately thirty percent of patients with insular carcinoid tumor. Carcinoid syndrome is rare in other types of primary ovarian carcinoid tumor. With the exception of mucinous carcinoid tumor, the prognosis is favorable. Primary ovarian mucinous carcinoid tumor has a more aggressive clinical course and it can metastasize to other anatomic sites.
A benign neoplasm arising from soft tissue of the ovary. It is characterized by the presence of spindle-shaped fibroblasts and increased cellularity.
A teratoma that arises from the ovary and is characterized by the presence of cystic structures. Representative example is the dermoid cyst.
An adult-type tumor that has derived from an ovarian dermoid cyst. Representative examples include dermoid cyst with secondary carcinoma, dermoid cyst with secondary sarcoma, and dermoid cyst with pituitary-type tumor.
A benign neoplasm of the ovary characterized by the presence of cystic structures lined by endometrial-type well-differentiated cells in a fibrotic stroma.
A benign, borderline, or malignant epithelial tumor of the ovary characterized by the presence of glands and/or cysts lined by neoplastic cells that resemble endometrial cells.
A usually aggressive malignant neoplasm arising from the ovary. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
A group of sex cord-stromal tumors that arise from the ovary. These tumors are characterized by the presence of granulosa cells, stromal cells, and/or theca cells. This group includes granulosa cell tumor and tumors of the thecoma/fibroma group.
An aggressive malignant smooth muscle neoplasm, arising from the ovary. It is characterized by a proliferation of neoplastic spindle cells.
A rare, benign steroid tumor that arises from the ovary and is composed of Leydig cells that contain Reinke crystals. It usually affects postmenopausal women and in most cases, is associated with androgenic manifestations.
A malignant adipose tissue neoplasm of the ovary.
A neoplasm that arises from the ovary and is characterized by the presence of germ cell and sex cord-stromal tissues that are intimately admixed. If there is no malignant germ cell component present, the clinical course is benign.
An invasive adenocarcinoma that arises from the ovary and is characterized by the presence of malignant epithelial cells that contain intracytoplasmic mucin. There is cellular atypia, increased layering of cells, complexity of glands, and papillary formations.
A benign, borderline, or malignant epithelial tumor of the ovary characterized by the presence of neoplastic epithelial cells that contain intracytoplasmic mucin and may resemble the epithelial cells of the endocervix or gastrointestinal tract.
A biphasic neoplasm that arises from the ovary and is characterized by the presence of mullerian-type epithelial tissue in a mesenchymal sarcomatous stroma. The presence of a high grade sarcomatous component is associated with recurrences and metastases.
A liposarcoma that arises from the ovary and is composed of round to oval mesenchymal cells, small signet ring lipoblasts, and a rich network of capillaries in a myxoid stroma.
An epithelial neoplasm with neuroendocrine differentiation that arises from the ovary. It includes carcinoid tumor, small cell carcinoma pulmonary type, and large cell neuroendocrine carcinoma.
A non-neoplastic disorder that affects the ovary. Representative examples include endometriosis and polycystic ovarian disease.
A carcinoma that arises from the ovary and is characterized by the presence of large malignant cells exhibiting neuroendocrine differentiation. The prognosis is poor.
A serous cystadenoma of the ovary characterized by the presence of small papillary projections in the inner surface of the cysts.
A malignant mesenchymal tumor with skeletal muscle differentiation affecting the ovaries.
An adenocarcinoma that arises from the ovary and is characterized by the presence of malignant epithelial cells that, in well differentiated tumors, resemble the epithelium of the fallopian tube or, in poorly differentiated tumors, show anaplastic features and marked nuclear atypia.
A serous adenocarcinoma that arises from the ovary and is characterized by the presence of a papillary architectural pattern.
A benign or malignant soft tissue neoplasm of the ovary. Representative examples include myxoma, fibroma, and sarcoma.
A mature teratoma that arises from the ovary and presents as a large solid mass. It contains multiple cysts that vary in size. Small foci of hemorrhage are also present.
A benign serous neoplasm characterized by the presence of papillary proliferations on the surface of the ovary.
A carcinoma that arises from the ovary and is characterized by the presence of malignant epithelial cells that resemble malignant urothelial cells. There is no morphologic evidence of a benign or borderline Brenner tumor component present.
A benign, borderline, or malignant epithelial tumor that arises from the ovary and is characterized by the presence of neoplastic cells that resemble urothelial cells and their neoplastic counterparts. This category includes benign Brenner tumor, borderline Brenner tumor, malignant Brenner tumor, and transitional cell carcinoma.
An internationally developed presurgical anatomic staging system using imaging techniques: Tumor involves only 1 quadrant; 3 adjoining liver quadrants are free of tumor. (from PDQ 2004)
An internationally developed presurgical anatomic staging system using imaging techniques: Tumor involves 2 adjoining quadrants; 2 adjoining quadrants are free of tumor. (from PDQ 2004)
An internationally developed presurgical anatomic staging system using imaging techniques: Tumor involves 3 adjoining quadrants or 2 nonadjoining quadrants; 1 quadrant or 2 nonadjoining quadrants are free of tumor. (from PDQ 2004)
An internationally developed presurgical anatomic staging system using imaging techniques: Tumor involves all 4 quadrants; there is no quadrant free of tumor. (from PDQ 2004)
A myofibroblastoma arising from the inguinal lymph nodes. It is characterized by the presence of nuclear palisading.
A carcinoma that arises from the pancreas showing both ductal and squamous differentiation. The squamous component should represent at least 30% of the malignant cellular infiltrate. The prognosis is usually worse than that of ductal adenocarcinoma.
A malignant, ectopic ACTH secreting pancreatic neuroendocrine tumor, associated with Cushing's syndrome. The prognosis is usually poor.
A usually malignant neuroendocrine tumor arising from the delta cells of the pancreas. It may be associated with inappropriate secretion of somatostatin and an associated clinical syndrome, or it may be hormonally inactive (non-functioning).
An infiltrating adenocarcinoma that arises from the epithelial cells of the pancreas. It affects males more often than females and the patients are usually over 50 years of age. Microscopically it is characterized by the presence of glandular (ductal) differentiation and desmoplastic stroma formation. Signs and symptoms include pain, loss of weight, and jaundice. It grows rapidly and is usually detected after it has metastasized to other anatomic sites. The prognosis is usually poor.
A pancreatic ductal adenocarcinoma characterized by the presence of adenocarcinoma cells with foamy cytoplasm.
A malignant glandular neoplasm arising from the exocrine pancreas. Microscopically it is characterized by the presence of mucoid stroma formation, papillary patterns, and cystic changes. It has been associated with KRAS and Tp53 gene mutations.
A non-invasive pancreatic intraductal papillary mucinous neoplasm characterized by the presence of neoplastic epithelial cells that exhibit nuclear stratification, loss of polarity, and crowding. There is moderate nuclear hyperchromasia.
A lymphoma that arises from the pancreas with the bulk of the tumor localized to this organ. The vast majority of cases are non-Hodgkin lymphomas of B-cell phenotype and include mucosa-associated lymphoid tissue lymphomas, follicular lymphomas, and diffuse large B-cell lymphomas.
A non-metastasizing cystic epithelial neoplasm arising from the exocrine pancreas. It is composed of columnar, mucin-producing epithelial cells. It occurs almost exclusively in women. Large tumors are often accompanied by a palpable abdominal mass.
A usually malignant neuroendocrine tumor arising from the delta cells of the pancreas. It is not associated with a hormonal syndrome.
A non-Hodgkin lymphoma that arises from the pancreas with the bulk of the tumor localized to this organ. The vast majority of cases are of B-cell phenotype and include mucosa-associated lymphoid tissue lymphomas, follicular lymphomas, and diffuse large B-cell lymphomas.
A pathologic process that arises from the pancreas and has the potential to evolve into a malignant neoplasm.
A metastasizing, slow-growing malignant epithelial neoplasm that arises from the exocrine pancreas. It is characterized by the presence of cysts and is composed of glycogen-rich malignant epithelial cells which produce a watery fluid. Signs and symptoms include upper gastrointestinal bleeding, weight loss, jaundice, and abdominal pain.
A benign, non-metastasizing cystic epithelial neoplasm arising from the exocrine pancreas. It is composed of glycogen-rich epithelial cells which produce a watery fluid. Signs and symptoms include abdominal mass, abdominal pain, nausea, vomiting, and weight loss.
A rare pancreatic ductal adenocarcinoma with poor prognosis. It is characterized by the presence of malignant signet ring cells infiltrating the pancreatic parenchyma in an individual cell pattern.
A benign or malignant papillary neoplasm that arises from the breast. It is characterized by the presence of epithelial proliferations that are supported by fibrovascular cores. Representative examples are intraductal papilloma and papillary carcinoma.
A squamous cell carcinoma that arises from the penis and is characterized by the presence of a papillary growth pattern.
Benign papillary proliferation within the ductal system of the breast parenchyma.
A morphologic variant of lung adenocarcinoma characterized by the presence of papillary structures.
A morphologic finding indicating the presence of a cellular infiltrate with papillary growth in a tissue sample.
A rare primary thymic adenocarcinoma, characterized by a papillary growth pattern.
A type of hyperplasia that is characterized by variable thickening of the urinary tract epithelium and a slight papillary growth. The latter is not associated with the presence of fibrovascular cores. There is no evidence of atypia. The relationship between this lesion and papillary urothelial neoplasia is not clear. -- 2003
A neoplastic lesion of the urinary tract transitional cell epithelium characterized by papillary formations. -- 2003
A benign primary melanocytic tumor of the skin that presents as a dermal nodule. Morphologically, it is characterized by the presence of paraganglioma-like features that include a nested growth pattern of the tumor cells. The nests are composed of epithelioid cells and are separated by delicate fibrous strands. Cytoplasmic melanin is not present; however immunohistochemical studies have confirmed the melanocytic lineage of the tumor cells.
An adenocarcinoma that arises from the paranasal sinuses. It is classified as intestinal-type or non-intestinal-type adenocarcinoma. Nasal obstruction and epistaxis are the presenting symptoms.
A rare adenoid cystic carcinoma that arises from the paranasal sinuses. It usually has an aggressive clinical course characterized by high recurrence rates and distant metastases.
A non-Hodgkin lymphoma that arises from the paranasal sinus and is characterized by the presence of a diffuse malignant infiltrate composed of large B-lymphocytes.
A lymphoma that arises from the paranasal sinus. Representative examples include diffuse large B-cell lymphoma and extranodal NK/T-cell lymphoma, nasal type.
A rare carcinoma that arises from the paranasal sinus. It is characterized by the presence of epidermoid cells, mucus producing cells, and cells of intermediate type.
A non-Hodgkin lymphoma that arises from the paranasal sinus. Representative examples include diffuse large B-cell lymphoma and extranodal NK/T-cell lymphoma, nasal type.
A malignant soft tissue neoplasm that arises from the paranasal sinus.
A papilloma that arises from the ciliated respiratory mucosa that lines the paranasal sinuses. It is classified as inverted papilloma and oncocytic papilloma.
A sensory neuropathy caused by the effects of a distant neoplasm (usually a small cell carcinoma). It is usually caused by the production of anti-neuronal autoantibodies: anti-Hu (ANNA-1) or anti-CV2 (CRMP-5), which result in cytotoxic T-cell mediated destruction of dorsal root ganglia. It is the most common clinical presentation of paraneoplastic encephalomyelitis. Clinical signs include asymmetric paresthesia of the face, trunk and proximal extremities followed by lancinating pain, vibrioceptive and proprioceptive impairment, and muted reflexes. Clinical course usually follows a progressive neurologic deterioration which stabilizes at a level of severe, permanent disability.
A rare benign adipose tissue neoplasm of the paratesticular tissues. It is incidentally discovered and presents as a non-tender scrotal mass. It affects patients over a wide age range.
A parathyroid gland adenoma composed predominantly or entirely of neoplastic cells with abundant granular eosinophilic cytoplasm.
Malignant epithelial tumor arising in the accessory urethral glands.
An adenocarcinoma with serous acinar cell differentiation that arises from the parotid gland. Patients usually present with a slow growing mass in the parotid area.
An adenocarcinoma that arises from the parotid gland. Representative examples include acinic cell carcinoma, basal cell adenocarcinoma, cystadenocarcinoma, and oncocytic carcinoma.
An aggressive carcinoma that arises from the parotid gland. It is characterized by the presence of malignant epithelial and myoepithelial cells forming cribriform, tubular, and solid patterns. It usually presents as a slow growing mass. Patients develop pain because of the tendency of these carcinomas to invade perineural tissues.
A carcinoma that arises from a pleomorphic adenoma in the parotid gland. Patients usually present with a history of a long-standing tumor mass which grew rapidly in the past few months. Patients with non-invasive or minimally invasive carcinoma have an excellent prognosis. In cases where there is invasion of the surrounding tissues, the clinical course is aggressive.
An aggressive, high grade malignant tumor that arises from the parotid gland. It is characterized by the presence of a malignant epithelial and a sarcomatous component.
A hemangioma arising from the parotid gland.
A Kaposi sarcoma arising from the parotid gland.
A rare benign adipose tissue neoplasm of the major salivary gland. It predominantly occurs in males.
A lymphangioma arising from the parotid gland.
A benign epithelial neoplasm that arises from the parotid gland. It is characterized by the presence of a monomorphic cellular infiltrate.
A carcinoma that arises from the parotid gland. It usually presents as a firm and painless mass. It is characterized by the presence of epidermoid cells, mucus producing cells, and cells of intermediate type. It usually spreads to pre-auricular lymph nodes. The majority of cases have a favorable outcome.
A low-grade extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue arising from the parotid gland. It is the most common type of non-Hodgkin lymphoma in the parotid gland and is often associated with Sjogren syndrome. The prognosis is favorable.
A non-Hodgkin lymphoma that arises from the parotid gland. Representative examples include mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma.
A rare, benign epithelial neoplasm that arises from the parotid gland. It is composed of irregular proliferating nests and islands of epithelium, including solid and gland-like sebaceous elements, surrounded by lymphoid stroma. Patients present with a progressively enlarging and painless mass.
An invasive squamous cell carcinoma that arises from the parotid gland. It usually affects elderly patients and presents as a rapidly enlarging tumor mass, often associated with pain.
A lesion connected to the underlying tissue by a small stalk.
A Kaposi sarcoma arising from the penis.
A non-neoplastic disorder that affects the penis. Representative examples include phimosis, balanitis, and hypospadias.
An adenocarcinoma that arises from the periampullary region.
Carcinoma that has spread diffusely to the pericardium.
A benign smooth muscle neoplasm arising from the pericardium. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A Malignant mesothelioma originating from cells of the pericardium (the thin layer of mesothelium lining the heart).
A hemangioma arising from perineural tissues.
A meningioma that affects the periocular region.
A ganglioneuroblastoma arising from the peripheral nervous system.
A malignant vascular neoplasm arising from the peripheral nerves.
A tumor composed of mature adipocytes and fibrous tissue infiltrating the epineurium and peripheral nerves. It is often seen at birth or during childhood and may be associated with macrodactyly.
A benign papillary neoplasm that arises in a terminal ductal lobular unit. It is characterized by the presence of a fibrovascular core that is lined by benign epithelial and myoepithelial proliferations. Peripheral breast papillomas are often multiple and are usually found microscopically. Patients are often asymptomatic.
A benign or malignant, primary or metastatic neoplasm involving the walls and/or cavities of the abdomen, pelvis, and retroperitoneal space.
A benign or malignant mesenchymal neoplasm arising from the perivascular cells of the connective and soft tissues. It is characterized by the presence of pericytes that grow in a circumferential pattern around vessels.
A meningioma that affects the petroclival region.
A meningioma that affects the petrous apex.
A non-neoplastic polyp that arises from the stomach and is characterized by the presence of smooth muscle branching bands, and hyperplasia with cystic dilatation of the foveolar epithelium.
An adenoid cystic carcinoma that arises from the pharynx.
An unusual, biphasic benign or malignant neoplasm that arises from the prostate gland. It is characterized by the presence of an epithelial glandular component and a proliferating stroma.
A hamartoma characterized by localized pilosebaceous apparatus malformation.
A fluid filled sac within the pineal gland. It is usually an incidental finding of no real clinical significance.
A meningioma that affects the pineal gland.
A mature or immature teratoma that arises in the pineal region.
A meningioma that affects the pituitary stalk.
A non-neoplastic disorder that arises from the placenta. Representative examples include chorioamnionitis, infarction, and malformations.
A lymphoproliferative disorder that develops following an organ transplantation and exhibits plasma cell myeloma features.
An early post-transplant lymphoproliferative lesion characterized by plasmacytic proliferation and architectural preservation of the involved tissues. It often regresses either spontaneously or after reduction in immunosuppression. The immunoglobulin genes are not rearranged. In some cases, a polymorphic or monomorphic post-transplant lymphoproliferative disorder may follow this early lesion.
Carcinoma that has spread diffusely to the pleura.
A benign adipose tissue neoplasm of the pleural cavity. It may be purely intra-thoracic or extend to the chest wall.
A disorder affecting a network of nerves, blood vessels, or lymph vessels.
An angiosarcoma characterized by the presence of significant cytologic atypia, necrosis and high mitotic activity.
A usually aggressive malignant neoplasm arising from the deep soft tissue. It is characterized by the presence of poorly-differentiated spindle-shaped fibroblasts, collagenous stroma formation and increased mitotic activity.
An invasive prostate adenocarcinoma characterized by the presence of malignant cells exhibiting poor differentiation.
A laboratory test result that indicates that a specific disease, condition, or attribute being assessed is present.
A meningioma that affects the posterior cranial fossa.
A meningioma that affects the posterior foramen magnum.
A carcinoma that arises from the posterior wall of the pharynx.
A squamous cell carcinoma that arises from the posterior wall of the pharynx.
An adenoid cystic carcinoma arising from the minor salivary glands in the base of the tongue.
A mucoepidermoid carcinoma arising from the minor salivary glands in the base of the tongue.
A benign, reactive lesion of the bladder, occurring status post bladder instrumentation; histologic exam demonstrates a fascicular growth pattern of plump or elongated spindle cells infiltrating the bladder wall without atypia or necrosis.
No distant metastases, tumor unresectable or resected with gross residual tumor, or positive lymph nodes. (from PDQ 2004)
No metastases, tumor grossly resected with microscopic residual disease (i.e., positive margins); or tumor rupture, or tumor spill at the time of surgery. (from PDQ 2004)
Distant metastases, regardless of the extent of liver involvement. (from PDQ 2004)
No metastases, tumor completely resected. (from PDQ 2004)
A polyp with severe dysplastic features.
A neoplasm of immature malignant lymphocytes (lymphoblasts) committed to the B-cell or T-cell lineage. Neoplasms involving the bone marrow and the peripheral blood are called precursor lymphoblastic leukemias or acute lymphoblastic leukemias. Neoplasms involving primarily lymph nodes or extranodal sites are called lymphoblastic lymphomas. -- 2003
A hematologic disorder which does not display the morphologic and/or clinical characteristics of an overt malignancy. Representative examples include atypical lymphoproliferative disorders and myelodysplastic syndromes.
A neoplasm that is composed of dysplastic cells and there is no morphologic evidence of infiltration of the surrounding tissues.
A chondrosarcoma arising from the central portion of bone without a benign precursor.
An anaplastic large cell lymphoma that affects the brain, meninges, or spinal cord.
An extranodal Burkitt lymphoma that arises from the stomach with the bulk of the mass located in the stomach.
An extranodal diffuse large B-cell lymphoma that arises from the stomach with the bulk of the mass located in the stomach.
A rare, extranodal T-cell non-Hodgkin lymphoma that arises from the stomach with the bulk of the mass located in the stomach.
A non-keratinizing or keratinizing squamous cell carcinoma that arises centrally from the jaw. It is characterized by a solid pattern, infiltration of the marrow spaces, and osseous resorption.
A rare squamous cell carcinoma that arises centrally from the jaw from the lining of an odontogenic cyst.
A rare meningioma that is present in the lung without clinical or radiologic evidence of central nervous system involvement.
A non-Hodgkin lymphoma that arises from the breast. There is no history of extramammary breast non-Hodgkin lymphoma and ipsilateral axillary lymph node involvement does not exclude the diagnosis of primary breast non-Hodgkin lymphoma. Most patients present with a painless breast lump. The vast majority of cases are B-cell non-Hodgkin lymphomas. Diffuse large B-cell lymphoma, follicular lymphoma, and extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue are the most common types of primary non-Hodgkin lymphoma of the breast.
A CD30 (Ki-1)-positive anaplastic large cell lymphoma with cytoplasmic and/or nuclear expression of the ALK (anaplastic lymphoma kinase) protein. It usually affects both the lymph nodes and extranodal sites (primarily skin, bones, lungs, and soft tissues), and has been associated with a favorable clinical outcome. -- 2004
A T-cell non-Hodgkin lymphoma that arises from the breast as a primary tumor. Primary T-cell non-Hodgkin lymphomas of the breast are rare.
A central nervous system embryonal tumor, not otherwise specified which has spread from its original site to the leptomeninges surrounding the brain and spinal cord.
The term refers to the treatment that was performed in the effort to cure the neoplastic disease before (prior) the current or being currently planned treatment regimen or given clinical event. Primary treatment is usually surgery, chemotherapy, or radiation therapy, or combination of some or all modalities listed above.
A disease process that is increasing in scope or severity.
Breast fibrocystic change characterized by the presence of epithelial cell hyperplasia. There is no evidence of epithelial atypia.
An adenoid cystic carcinoma that arises from the prostate gland.
An infrequent invasive carcinoma of the prostate gland characterized by the presence of both glandular and squamous neoplastic components. It is more often located in the transitional zone of the prostate gland and it tends to rapidly metastasize to the bones.
A malignant vascular neoplasm arising from the prostate.
A carcinoma that arises from the prostate gland and has spread to the bone.
A carcinoma that arises from the prostate gland and has spread to the lungs.
A malignant mesenchymal neoplasm of the prostate. It is characterized by the presence of skeletal muscle exhibiting embryonic features.
A Kaposi sarcoma arising from the prostate.
A benign smooth muscle neoplasm arising from the prostate. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the prostate. It is characterized by a proliferation of neoplastic spindle cells.
A rare non-Hodgkin or Hodgkin lymphoma that arises from the prostate gland.
A usually aggressive morphologic variant of acinar adenocarcinoma of the prostate gland characterized by the presence of lakes of extracellular mucin. This diagnosis applies when at least 25% of the resected tumor contains extracellular mucin.
Myeloid sarcoma that affects the prostate gland. It may present in association with or as a site of relapse of acute myeloid leukemia. Cases of myeloid sarcoma of the prostate gland preceding acute myeloid leukemia have also been reported.
A neoplasm with neuroendocrine differentiation that arises from the prostate gland. This category includes carcinoid tumors and small cell carcinomas.
A rare non-Hodgkin lymphoma that arises from the prostate gland.
A non-neoplastic disorder that affects the prostate gland. Representative examples include acute and chronic prostatitis.
A malignant mesenchymal neoplasm with skeletal muscle differentiation affecting the prostate.
A rare morphologic variant of acinar adenocarcinoma of the prostate gland with unfavorable prognosis, composed of both malignant glandular and sarcomatous components. The sarcomatous component contains a malignant spindle cell proliferation or specific mesenchymal elements including osteosarcoma, chondrosarcoma, and leiomyosarcoma.
A morphologic variant of acinar adenocarcinoma of the prostate gland characterized by the presence of signet ring malignant cells.
A rare malignant neoplasm arising from specialized prostatic stroma. It is characterized by the presence of stromal overgrowth and hypercellularity, increased number of mitotic figures, and pleomorphism.
A prostatic hyperplasia characterized by the presence of crowded adenomatous epithelial nodules.
An epithelioid sarcoma predominantly involving the pelvis, perineum, and genital organs. It tends to have a more aggressive clinical course as compared to the more frequently seen distal-type epithelioid sarcoma.
A morphologic finding indicating the presence of poorly cohesive neoplastic cells arranged around fibrovascular cores in a tissue sample.
A malignant vascular neoplasm arising from the pulmonary artery.
A rare choriocarcinoma that arises from a pulmonary artery.
An aggressive malignant smooth muscle neoplasm, arising from the pulmonary artery It is characterized by a proliferation of neoplastic spindle cells.
A premalignant pathologic process that affects the lungs. This category includes bronchial intraepithelial neoplasia and atypical adenomatous hyperplasia.
A neoplasm originating from the apical lung. Most superior sulcus neoplasms are bronchogenic carcinomas. This tumor may be associated with Pancoast syndrome. It is also known as Pancoast tumor.
An aggressive malignant smooth muscle neoplasm, arising from the pulmonary vein. It is characterized by a proliferation of neoplastic spindle cells.
Pure erythroid leukemia that is responding to therapy, i.e. It is not progressing and possibly regressing.
A carcinoma that arises from the pyriform sinus. Patients usually present with advanced stage disease and the prognosis is poor.
A morphologic architectural pattern in which the tumor cells spread horizontally.
A meningioma that arises within the cranial cavity and results from exposure to radiation.
A malignant vascular neoplasm arising in an anatomic site exposed to radiation therapy.
A benign, epidermal skin lesion characterized by overexpression of collagen during wound healing.
An adenoma that arises from the rectum. It is characterized by the presence of severe epithelial dysplasia.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the rectum. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A serrated polypoid lesion that arises in the rectum. It rarely produces symptoms. This group includes goblet cell rich, mucin poor, and microvesicular hyperplastic polyps.
A non-neoplastic hamartomatous polyp that arises from the rectum. It is characterized by the presence of tortuous and cystically dilated glands, edematous changes, and inflammation.
A Kaposi sarcoma arising from the rectum.
A well-circumscribed benign smooth muscle neoplasm arising from the rectum. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm that arises from the rectum. It is characterized by a proliferation of neoplastic spindle cells.
A benign adipose tissue neoplasm of the rectum.
An extranodal lymphoma that arises from the rectum. The majority are B-cell non-Hodgkin lymphomas.
A neoplasm with neuroendocrine differentiation that arises from the rectum. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A malignant mesenchymal tumor with skeletal muscle differentiation affecting the rectum.
A malignant soft tissue neoplasm that arises from the rectum. Representative examples include angiosarcoma, Kaposi sarcoma, and leiomyosarcoma.
A biphasic rectal carcinoma with a spindle cell, sarcomatoid component.
A very rare rectal carcinoma characterized by the presence of a malignant squamous cell infiltrate.
A neoplasm that arises from the glandular epithelium of the rectal mucosa. It is characterized by tubular and villous architectural patterns. The neoplastic glandular cells have dysplastic features.
The reemergence of anaplastic large cell lymphoma after a period of remission.
The reemergence of Ewing sarcoma of the bone after a period of remission.
The reemergence of brain stem astrocytoma in childhood after a period of remission.
The reemergence of central nervous system neoplasm in childhood after a period of remission.
The reemergence of optic nerve astrocytoma in childhood after a period of remission.
The reemergence of visual pathway astrocytoma in childhood after a period of remission.
The reemergence of female reproductive system carcinoma after a period of remission.
The reemergence of follicular lymphoma after a period of remission.
The reemergence of carcinoma in any part of the digestive system after a period of remission.
The reemergence of carcinoma in the head and neck region after a period of remission.
The reemergence of a carcinoma that affects the male reproductive system after a period of remission.
The reemergence of a malignant neoplasm of the endocervix after a period of remission.
The reemergence of a malignant neoplasm of the stomach after a period of remission.
A malignant tumor of neural sheath origin-lesions reappearing after an intermission or remission.
The reemergence of mature T- and NK-cell non-Hodgkin lymphoma after a period of remission.
The reemergence of medulloblastoma after a period of remission.
The reemergence of a meningioma after a period of remission.
The reemergence of metastatic squamous cell carcinoma of unknown primary in the neck region after a period of remission.
The reemergence of nodular lymphocyte predominant Hodgkin lymphoma after a period of remission.
The reemergence of carcinoma in the oral cavity after a period of remission.
The reemergence of a small round cell tumor with neural differentiation after a period of remission.
The reemergence of a primitive neuroectodermal tumor of the central or the peripheral nervous system after a period of remission.
Follicular lymphoma grade I, II, III that is resistant to treatment.
A hematologic malignancy that is resistant to treatment.
Mature T-cell and NK-cell non-Hodgkin Lymphoma resistant to treatment.
Nodular lymphocyte predominant Hodgkin lymphoma that is resistant to treatment.
A medulloblastoma characterized by the loss of one of the p13 regions of chromosome 17. Loss of genetic material of chromosome arm 17p is the most common molecular genetic abnormality found in medulloblastomas.
A benign neoplasm arising from the kidney. It is characterized by the presence of spindle-shaped fibroblasts.
An aggressive malignant smooth muscle neoplasm, arising from the kidney. It is characterized by a proliferation of neoplastic spindle cells.
A rare benign adipose tissue neoplasm of the kidney. It predominantly affects middle-aged females. It may originate from renal parenchymal fat or fat cells within the renal capsule. Clinical presentation includes hematuria and pain.
A rare malignant adipose tissue neoplasm of the fat cells surrounding the kidney, usually of the well-differentiated or myxoid type. It may be associated with tuberous sclerosis.
A distinctive epithelioid renal neoplasm often affecting young patients, bearing a characteristic t(6;11)(p21;q12) chromosomal translocation resulting in Alpha-TFEB gene fusion. -- 2004
An osteosarcoma arising from the kidney.
A carcinoma arising in the renal pelvis. The majority of renal pelvis carcinomas are transitional cell and less frequently squamous cell carcinomas.
A benign, mesodermal tumor located in the renal pelvis.
A neoplasm of the renal pelvis in which the epithelial cells grow downward into the underlying supportive tissue.
An infiltrating transitional cell carcinoma that arises from the renal pelvis and exhibits sarcomatoid features.
An aggressive malignant smooth muscle neoplasm, arising from the renal vein. It is characterized by a proliferation of neoplastic spindle cells.
A benign or malignant endocrine neoplasm that arises from the testis or the ovary.
Symptoms, physical examination results, and/or laboratory test results related to the reproductive system.
Increased reticular fiber deposition within bone marrow.
A ganglioneuroma arising from the retroperitoneum.
A benign or malignant hemangiopericytoma arising from the retroperitoneum.
A benign mesenchymal neoplasm arising from the central nervous system. It consists of mature skeletal muscle tissue.
A meningioma that arises from the meninges of the sacral region of the spinal cord.
A rare, aggressive carcinoma that arises from the salivary glands. It is characterized by the presence of a squamous and a glandular epithelial component.
A benign epithelial neoplasm primarily composed of branching and interconnecting cords of single and double-cell thick rows of columnar epithelium in a very loose stroma. It often occurs in the upper lip, where only pleomorphic adenoma is more frequent. Asymptomatic swelling of the upper lip is the most common clinical finding. It may present clinically and histologically as a multifocal lesion, a feature not generally seen with other intraoral salivary gland tumors.
A rare, low-grade adenocarcinoma that arises from the salivary glands. It presents as a slow growing asymptomatic mass and is characterized by the presence of multiple cystic spaces.
An uncommon benign epithelial tumor, characterized by predominantly unicystic or multicystic growth; there is focal intraluminal papillary proliferation of the lining epithelium. Nearly half occur in the parotid gland. In the minor salivary glands, women are affected more than men. In the major salivary glands, cystadenomas present as slowly enlarging, asymptomatic masses that may be slightly compressible. Cystadenocarcinoma is the malignant counterpart.
A benign papillary neoplasm that arises from the salivary glands. This category includes intraductal papilloma, inverted ductal papilloma, and sialadenoma papilliferum.
A carcinoma that arises from the salivary glands, most often the parotid gland. It presents as a slow growing and painless mass. It is characterized by the presence of duct-like structures lined by two layers of cells, an inner layer composed of epithelial-type cells and an outer layer composed of clear, myoepithelial-type cells.
An intraluminal papillary proliferation that causes unicystic dilatation of the duct and may have features in common with papillary cystadenoma. It is quite rare, and involves almost exclusively the excretory ducts of intraoral minor salivary glands. It presents as an asymptomatic submucosal swelling. -- 2003
A very rare benign tumor of the minor salivary glands, characterized by a luminal papillary proliferation that arises at the junction of the salivary gland duct and the oral mucosal surface epithelium and expands as a nodular mass into the lamina propria. It presents as an asymptomatic mucosal swelling.
A carcinoma that arises from the salivary glands. It is the most common primary carcinoma of the salivary glands and usually presents as a firm and painless mass. It is characterized by the presence of epidermoid cells, mucus producing cells, and cells of intermediate type. The majority of cases have a favorable outcome.
A locally aggressive carcinoma that arises from the salivary glands, predominantly the parotid gland. It is characterized by the presence of a malignant cellular infiltrate which exhibits myoepithelial differentiation. Patients usually present with a painless mass.
A benign epithelial neoplasm composed of layers of oncocytes (small round nucleus, micro-granular, eosinophilic cytoplasm with numerous tightly-packed mitochondria. [NCIT:C5932, PMID:20181155]
A low grade malignant epithelial neoplasm arising from the salivary gland. It usually arises from the oral cavity, with approximately 60% of the cases involving the palate. The most common presenting sign is a painless mass in the palate. It is characterized by the presence of uniform, small to medium size malignant epithelial cells and an infiltrating pattern. There is a variety of morphologic patterns which may be present within an individual tumor, including lobular, papillary, papillary-cystic, cribriform, and trabecular pattern. It usually has a favorable clinical outcome and a low metastatic potential.
A rare, benign, encapsulated epithelial tumor composed of cells that form solid, variably shaped islands and cysts, both showing focal sebaceous differentiation. The mean age of patients is reported to be 58 years, and most tumors occur in the parotid gland. There is a male predominance. Most patients are asymptomatic. -- 2003
A rare, benign epithelial neoplasm composed of irregular proliferating nests and islands of epithelium, including solid and gland-like sebaceous elements, surrounded by lymphoid stroma. Most occur in the parotid gland. Symptoms include a progressively enlarging, painless mass. Sebaceous lymphadenocarcinoma is the malignant counterpart.
An uncommon exophytic papillary proliferation that involves mucosal surface epithelium and salivary duct epithelium. It is exceptional among salivary gland neoplasms because it manifests as an exophytic papillary excrescence of the mucosa, rather than as a submucosal or intraglandular mass. It most often affects the hard or soft palate. It is generally asymptomatic. -- 2003
A rare, congenital or perinatal, aggressive and potentially low-grade malignant, basaloid neoplasm that occurs in the major salivary glands. It typically presents as a mass over the angle of the mandible. Most involve the parotid gland.
A sarcoma with a total score of 2 or 3 according to the FNCLCC guidelines.
A sarcoma with a total score of 4 or 5 according to the FNCLCC guidelines.
A sarcoma with a total score of 6 or higher according to the FNCLCC guidelines.
Grading of sarcomas according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC). This sarcoma grading system is based on three factors: differentiation, mitotic count, and tumor necrosis. The scores for each factor are added to determine the grade (1 to 3) for the sarcoma.
A squamous cell carcinoma that arises from the penis and is characterized by the presence of malignant spindle-shaped cells.
A rare, usually aggressive, primary thymic carcinoma, characterized by the presence of tumor cells morphologically resembling soft tissue sarcoma.
Schwannomatosis is characterized by a predisposition to develop multiple schwannomas and, less frequently, meningiomas. Individuals with schwannomatosis most commonly present between the second and fourth decade of life. The most common presenting feature is localized or diffuse pain or asymptomatic mass. Schwannomas most often affect peripheral nerves and spinal nerves. Meningiomas occur in about 5% of individuals with schwannomatosis and have only been reported in individuals with SMARCB1-related schwannomatosis. Malignancy remains a theoretic risk especially in individuals with a SMARCB1 pathogenic variant.
Breast adenosis characterized by the proliferation of acini, a lobulated architectural pattern, and stromal sclerosis. The luminal epithelial and myopepithelial cells are preserved. Microcalcifications and foci of apocrine metaplasia may be present.
A breast papilloma characterized by the presence of predominant sclerosing architectural features.
A hemangioma arising from the skin of the scrotum.
A Hodgkin lymphoma that has metastasized to the cerebral hemisphere following the initial presentation in another nodal or extranodal site.
A chondrosarcoma that arises either in a pre-existing enchondroma or close to the cartilaginous cap of a pre-existing osteochondroma.
A lymphoma that has spread to the heart from another primary anatomic site.
A broad classification of dysgammaglobulinemias characterized by low or undetectable serum levels of one of the five immunoglobulin classes. Deficiencies of immunoglobulins present variably according to isotype. Selective deficiencies may be caused by decreased or inefficient production from progenitor B cells without any corresponding decreases in the other isotypes. The clinical course and prognosis is dependent upon the severity of the selective deficiency and associated morbidity.
Attached directly by the base; not having an intervening stalk.
The non-catalytic beta subunit of Shiga toxin may be useful as a fusion vector for induction of antigen-specific cytotoxic T lymphocyte responses.
An invasive breast adenocarcinoma characterized by the presence of malignant epithelial cells with signet ring appearance.
A poorly cohesive gastric adenocarcinoma characterized by malignant cells containing intracytoplasmic mucin.
A proliferation of endometrial cells resulting in glandular enlargement and budding without changes in the basic structure of the endometrium. Epithelial atypia is present.
A proliferation of endometrial cells resulting in glandular enlargement and budding without changes in the basic structure of the endometrium. Epithelial atypia is absent.
HPV-negative vulvar squamous intraepithelial proliferation with abnormal keratinocyte differentiation and basal cell atypia. These lesions are most strongly linked to cancer by association rather than outcome. Risk of progression to invasion is unclear but can be rapid, often less than six months. Management is predicated on complete removal. (WHO, 2014)
A benign or malignant mesenchymal neoplasm arising from skeletal muscle.
A slow-growing malignant bone tumor arising from the remnants of the notochord and occurring in the base of the skull. It is characterized by a lobulated growth pattern, myxoid stroma formation, and the presence of physaliphorous cells..
A meningioma that arises from the skull base.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the extrahepatic bile ducts. It is characterized by the presence of malignant small cells.
An aggressive, small cell, poorly differentiated thymic neuroendocrine carcinoma, characterized by the presence of a high mitotic rate and numerous apoptotic bodies.
A hepatoblastoma composed exclusively of noncohesive sheets of small undifferentiated cells.
An infrequent small cell carcinoma that arises from the salivary glands and is characterized by the presence of a high number of mitotic figures.
A histologic variant of anaplastic large cell lymphoma characterized by the presence of a predominant population of small to medium size malignant cells with irregular nuclei.
A morphologic variant of Burkitt lymphoma that arises from the small intestine. It is characterized by marked nuclear pleomorphism, abundant apoptotic debris, and the presence of tangible body macrophages.
A Burkitt lymphoma that arises from the small intestine.
A somatostatin-producing neuroendocrine tumor that arises from the small intestine. It is characterized by the presence of tubulo-glandular structures.
A usually aggressive malignant neoplasm arising from the small intestine. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
A gastrointestinal stromal tumor that arises from the small intestine. It usually affects adults over fifty years of age. The majority of cases have spindle cell morphology. The prognosis depends on the tumor size and the mitotic activity.
A precancerous neoplastic process that affects the small intestine. It is characterized by moderate or severe epithelial dysplasia and complex architectural alterations of the mucosal epithelium. There is no evidence of invasion.
A Hodgkin lymphoma that arises from the small intestine.
A precancerous neoplastic process that affects the small intestine. It is characterized by low or high grade dysplasia of the mucosal epithelium. There is no evidence of invasion.
A rare benign adipose tissue neoplasm of the small intestine. It usually arises from the submucosa and occasionally protrudes into the lumen.
A precancerous neoplastic process that affects the small intestine. It is characterized by mild epithelial dysplasia and mild architectural alterations of the mucosal epithelium. There is no evidence of invasion.
A mantle cell lymphoma that arises from the small intestine. It may present as an isolated mass in the small intestine or as a part of the multiple lymphomatous polyposis.
A mucosa-associated lymphoid tissue lymphoma (MALT) that arises from the small intestine. The morphologic characteristics are similar to those seen in gastric MALT lymphomas, with the exception of the lymphoepithelial lesions that are less prominent in the small intestine.
A neoplasm with neuroendocrine differentiation that arises from the small intestine. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A B-cell or T-cell non-Hodgkin lymphoma that arises from the small intestine. Representative examples of B-cell non-Hodgkin lymphoma include diffuse large B-cell lymphoma, MALT lymphoma, alpha heavy chain disease/immunoproliferative small intestinal disease, Burkitt lymphoma, follicular lymphoma, and mantle cell lymphoma. The T-cell non-Hodgkin lymphomas are the enteropathy-associated T-cell lymphoma and the monomorphic CD56 positive intestinal T-cell lymphoma.
A malignant soft tissue neoplasm that arises from the small intestine. Representative examples include leiomyosarcoma, angiosarcoma, and Kaposi sarcoma.
An aggressive, high-grade, and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the small intestine. It is characterized by the presence of malignant small cells.
A neuroendocrine tumor that arises from the small intestine and produces vasoactive intestinal peptide.
Small lymphocytic lymphoma characterized by the presence of somatic hypermutation within the immunoglobulin heavy chain gene variable region of neoplastic clones. Patients have a better prognosis as compared to those with unmutated immunoglobulin heavy chain gene variable region rearrangements.
A small lymphocytic lymphoma characterized by the presence of neoplastic lymphocytes with plasmacytoid morphology.
Small lymphocytic lymphoma characterized by the absence of somatic hypermutation within the immunoglobulin heavy chain gene variable region of neoplastic clones. Patients have a significantly worse prognosis as compared to those with mutated immunoglobulin heavy chain gene variable region rearrangements.
An adult T-cell leukemia/lymphoma characterized by less than 5% neoplastic lymphocytes in the peripheral blood, absence of lymphadenopathy and hypercalcemia, and occasional skin or pulmonary lesions. -- 2004
A rare benign neoplasm that arises from the soft palate. It is characterized by the presence of plump eosinophilic cells with abundant granular cytoplasm. The neoplastic cells extend into the surrounding tissues. Recurrences are rare after removal of the tumor.
A benign, slow-growing and painless neoplasm that arises from the minor salivary glands in the soft palate. It is composed of cells that demonstrate both epithelial and mesenchymal differentiation.
A usually aggressive malignant neoplasm arising from the soft tissue. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
A morphologic variant of alveolar rhabdomyosarcoma. It is characterized by the presence of a solid growth pattern and the absence of fibrovascular stroma.
A morphologic variant of lung adenocarcinoma characterized by the presence of polygonal malignant cells forming sheets. Acinar, papillary, micropapillary, or lepidic growth patterns are absent. If the tumor is 100 percent solid, intracellular mucin should be present in at least five tumor cells in each of two high-power fields and confirmed with mucin immunohistochemical stains. Tumors formerly classified as large cell carcinomas expressing pneumocyte immunohistochemical markers, even if intracellular mucin is absent, are now included in this category.
A well circumscribed, low grade neoplasm that arises from the breast. It is characterized by the presence of sheets of malignant epithelial cells that are supported by fibrovascular structures. When there is an invasive component present, it is usually a mucinous carcinoma.
A microscopic finding indicating that the neoplastic cells are arranged in solid sheets in a tumor sample.
A malignant neoplasm arising from the exocrine pancreas. It occurs predominantly in young women. It is characterized by the presence of extensive necrosis and hemorrhage and is composed of polyhedral cells forming solid and pseudopapillary patterns. There is morphologic evidence of perineural invasion, vascular invasion, or extensive invasion into the surrounding tissues.
A low-grade malignant neoplasm that arises from the exocrine pancreas. It is characterized by the presence of uniform cells that form solid and pseudopapillary patterns, cystic changes, and hemorrhage. Perineural invasion, vascular invasion, and invasion into surrounding tissues may be present. It usually presents as an encapsulated, solitary, and lobulated pancreatic mass. It is usually found incidentally during physical examination or it may present with abdominal discomfort and pain. It occurs predominantly in young women. Complete removal of the tumor is curative in the majority of cases.
A solitary benign neoplasm arising from the fibrous soft tissues. The tumor is characterized by the presence of spindle-shaped fibroblasts.
A meningioma that affects the sphenocavernous region.
A benign neoplasm that arises from the ciliated respiratory mucosa that lines the sphenoid sinus. It results from the invagination and proliferation of epithelial cells in the underlying stroma.
A papilloma that arises from the ciliated respiratory mucosa that lines the sphenoid sinus. It is classified as inverted papilloma and oncocytic papilloma.
A squamous cell carcinoma that arises from the mucosal epithelial surface of the sphenoid sinus. Patients may present with nasal fullness, obstruction, and/or epistaxis.
A meningioma that affects the sphenoorbital region.
A non-Hodgkin or Hodgkin lymphoma that arises in the spinal cord as a primary lesion.
A neuroblastoma that affects the spinal cord.
A neurofibroma that arises from the spinal cord.
A central nervous system embryonal tumor, not otherwise specified arising from the spinal cord.
A sarcoma that arises from the spinal cord.
A clear cell meningioma arising in multiple areas of the spinal cord characterized by the presence of clear glycogen-rich polygonal cells.
A benign or malignant neoplasm characterized by the presence of neoplastic spindle cells.
A benign lipomatous neoplasm characterized by the presence of an admixture of mature adipose tissue and bland spindle cells. The pleomorphic variant contains in addition multinucleated giant cells. It usually arises in the neck and upper trunk in older males.
A uveal melanoma characterized by the presence of malignant spindle-shaped melanocytes with slender nuclei and no visible nucleoli.
A uveal melanoma characterized by the presence of malignant spindle-shaped melanocytes with larger nuclei and distinct nucleoli.
A gastrointestinal stromal tumor composed of neoplastic spindle cells.
Infiltration and expansion of the red pulp cords and sinusoids of the spleen by T-cell large granular lymphocyte leukemia. The white pulp of the spleen is not involved and is often hyperplastic.
A carcinoma that arises from the breast and is not caused by inherited genetic mutations.
A clinical variant of Burkitt lymphoma that occurs throughout the world. It affects both children and adults and is more frequently seen in males.
A papillary renal cell carcinoma that occurs in a patient who does not have a family history of papillary renal cell carcinoma nor is a carrier of an inherited DNA change that would increase the risk of developing this carcinoma.
A rare carcinoma that arises from the breast parenchyma and is entirely composed of squamous cells.
An intraepidermal squamous cell carcinoma involving the area of the nipple. -- 2003
A squamous cell carcinoma that arises from the penis and cannot be classified according to other morphologic subtypes.
A rare primary thymic carcinoma, characterized by the presence of keratinizing or non-keratinizing malignant squamous cells. Approximately 10-20% of cases occur in combination with thymoma. The prognosis depends on the tumor stage and the degree of cellular differentiation.
A term referring to neoplastic changes in the bronchial epithelium manifested as dysplasia.
A benign exophytic neoplasm that arises from the nasopharynx. It is characterized by the presence of a connective tissue core covered by stratified squamous epithelium.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th, 7th, and 8th eds.)
Stage 0 includes: 0a (Ta, N0, M0); 0is (Tis, N0, M0). Ta: Papillary noninvasive carcinoma. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage 0 includes: pTis, N0, M0, S0. pTis: Intratubular germ cell neoplasia (carcinoma in situ). N0: regional lymph node metastasis. M0: No distant metastasis. S0: Marker study levels within normal limits. (AJCC 6th and 7th eds.)
Stage 0 includes: 0a (Ta, N0, M0); 0is (Tis, N0, M0); (Tis pu, N0, M0); (Tis pd, N0, M0). Ta: Noninvasive papillary, polypoid, or verrucous carcinoma. Tis: Carcinoma in situ. Tis pu: Carcinoma in situ, involvement of the prostatic urethra. Tis pd: Carcinoma in situ, involvement of the prostatic ducts. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage 0a includes: Ta, N0, M0. Ta: Papillary noninvasive carcinoma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage 0a includes: Ta, N0, M0. Ta: Noninvasive papillary, polypoid, or verrucous carcinoma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IA1 includes: T1a1, N0, M0. T1a1: Measured stromal invasion 3.0 mm or less in depth and 7.0 mm or less in horizontal spread. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IA2 includes: T1a2, N0, M0. T1a2: Measured stromal invasion more than 3.0 mm and not more than 5.0 mm with a horizontal spread 7.0 mm or less. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IA includes: (T1a, N0, M0); (T1b, N0, M0). T1a: Lung cancer with a tumor size of 2 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a. T1b: Lung cancer with a tumor size more than 2 cm but 3 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). N0: No regional lymph metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IA includes: T1, N0, M0, G1, G2, GX. T1: Tumor 8 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated-low grade. G2: Moderately differentiated-low grade. GX: Grade cannot be assessed. (AJCC 7th ed.)
Stage IA includes: T1a, N0, M0. T1a: Tumor limited to the endometrium or invades less than one-half of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IA includes: T1a, N0, M0. T1a: Tumor limited to one tube, without penetrating the serosal surface; no ascites. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IA includes: T1, N0, M0. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IA includes: T1a, N0, M0. T1a: Tumor limited to one ovary; capsule intact, no tumor on ovarian surface. No malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IA includes: (T1a, N0, M0). T1a: Tumor limited to one ovary; capsule intact, no tumor on ovarian surface. No malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage IA includes: Tia, N0, M0. T1a: Tumor confined to the vulva or vulva and perineum, 2cm or less in greatest dimension, and with stromal invasion no greater than 1mm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage IB1 includes: T1b1, N0, M0. T1b1: Clinically visible lesion 4.0 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IB2 includes: T1b2, N0, M0. T1b2: Clinically visible lesion more than 4.0 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IB includes: T2a, N0, M0. T2a: Lung cancer with a tumor size more than 3 cm but 5 cm or less in greatest dimension. N0: No regional lymph metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IB includes: (T2, N0, M0, G1, G2, GX); (T3, N0, M0, G1, G2, GX). T2: Tumor more than 8 cm in greatest dimension. T3: Discontinuous tumors in the primary bone site. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated-low grade. G2: Moderately differentiated-low grade. GX: Grade cannot be assessed. (AJCC 7th ed.)
Stage IB includes: T1b, N0, M0. T1b: Tumor invades one-half or more of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IB includes: T1b, N0, M0. T1b: Tumor limited to both tubes, without penetrating the serosal surface; no ascites. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IB includes: (T2, N0, M0); (T1, N1, M0). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IB includes: T1b, N0, M0. T1b: Tumor limited to both ovaries; capsules intact, no tumor on ovarian surface. No malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IB includes: (T1b, N0, M0). T1b: Tumor limited to both ovaries; capsules intact, no tumor on ovarian surface. No malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage IB includes: T1b, N0, M0. T1ab Tumor confined to the vulva or vulva and perineum, 2cm or less in greatest dimension, and with stromal invasion greater than 1mm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage IC includes: T1c, N0, M0. T1c: Tumor limited to one or both tubes with extension onto or through the tubal serosa, or with malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IC includes: T1c, N0, M0. T1c: Tumor limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IC includes: (T1c, N0, M0). T1c: Tumor limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage IIA includes: (T2b, N0, M0); (T1a, N1, M0); (T1b, N1, M0); (T2a, N1, M0). T2b: Lung cancer with a tumor size more than 5 cm but 7 cm or less in greatest dimension. T1a: Lung cancer with a tumor size of 2 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a. T1b: Lung cancer with a tumor size more than 2 cm but 3 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). T2a: Lung cancer with a tumor size more than 3 cm but 5 cm or less in greatest dimension. N0: No regional lymph node metastasis. N1: Lung cancer with metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary lymph nodes, including involvement by direct extension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIA includes: T1, N0, M0, G3, G4. T1: Tumor 8 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G3: Poorly differentiated. G4: Undifferentiated. (AJCC 7th ed.)
Stage IIA includes: (T0, N1, M0); (T1, N1, M0); (T2, N0, M0). T0: No evidence of primary tumor. T1: Tumor 20 mm or less in greatest dimension. T1 includes T1mi. T1mi: Tumor 1 mm or less in greatest dimension. T2: Tumor more than 20 mm but not more than 50 mm in greatest dimension. N1: Metastasis to movable ipsilateral level I, II axillary lymph node(s). N0: No regional lymph node metastasis. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 6th and 7th Eds.)
Stage IIA includes: T2, N0, M0, G3. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. G3: Poorly differentiated. (AJCC 7th ed.)
Stage IIA includes: For squamous cell carcinoma: (T2-3, N0, M0, G1, GX, Tumor location: Upper, middle); (T2-3, N0, M0, G2-3, Tumor location: Lower, X). For adenocarcinoma: (T2, N0, M0, G3). T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IIA includes: (T2-3, N0, M0, G1, GX, Tumor location: Upper, middle); (T2-3, N0, M0, G2-3, Tumor location: Lower, X). T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IIA includes: T2a, N0, M0. T2a: Extension and/or metastasis to the uterus and/or ovaries. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIA includes: T2a, N0, M0. T2a: Extension and/or implants on uterus and/or tube(s). No malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIB includes: (T2b, N1, M0); (T3, N0, M0). T2b: Lung cancer with a tumor size more than 5 cm but 7 cm or less in greatest dimension. T3: Lung cancer with a tumor size more than 7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumor in the main bronchus (less than 2 cm distal to the carina but without involvement of the carina); or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe. N0: No regional lymph node metastasis. N1: Lung cancer with metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary lymph nodes, including involvement by direct extension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: T2, N0, M0, G3, G4. T2: Tumor more than 8 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G3: Poorly differentiated. G4: Undifferentiated. (AJCC 7th ed.)
Stage IIB includes: (T2, N1, M0); (T3, N0, M0). T2: Tumor more than 20 mm but not more than 50 mm in greatest dimension. T3: Tumor more than 50 mm in greatest dimension. N1: Metastasis to movable ipsilateral level I, II axillary lymph node(s). N0: No regional lymph node metastasis. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 6th and 7th Eds.)
Stage IIB includes: (T3, N0, M0, Any G); (T1-2, N1, M0, Any G). T3: Tumor invades adventitia. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: For squamous cell carcinoma: (T2-3, N0, M0, G2-3, Tumor location: Upper, middle); (T1-2, N1, M0, Any G, Tumor location: Any). For adenocarcinoma: (T3, N0, M0, Any G); (T1-2, N1, M0, Any G). T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IIB includes: (T2-3, N0, M0, G2-3, Tumor location: Upper, middle); (T1-2, N1, M0, Any G, Tumor location: Any). T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. M0: No distant metastasis. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IIB includes: T2b, N0, M0. T2b: Extension to other pelvic structures. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIB includes: (T3b, N0, M0); (T4a, N0, M0). T3b: Cutaneous melanoma with a tumor measuring 2.01-4.0 mm in thickness, with ulceration. T4a: Cutaneous melanoma with a tumor measuring more than 4.0 mm in thickness, without ulceration. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 6th and 7th Eds.)
Stage IIB includes: T2b N0, M0. T2b: Extension and/or implants on other pelvic tissues. No malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIC includes: T2c, N0, M0. T2c: Pelvic extension with malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIC includes: T2c, N0, M0. T2c: Pelvic extension and/or implants (T2a or T2b) with malignant cells in ascites or peritoneal washing. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIC includes: (Any pT/TX, N3, M0, S0); (Any pT/TX, N3, M0, S1). pTX: Primary tumor cannot be assessed. N3: Metastasis with a lymph node mass more than 5 cm in greatest dimension. M0: No distant metastasis. S0: Marker study levels within normal limits. S1: LDH less than 1.5 x N (N indicates the upper limit of normal for the LDH assay) and hCG less than 5,000 and AFP less than 1,000. (AJCC 6th and 7th eds.)
Stage IIIA includes: T3a, N0, M0. T3a: Tumor involves lower third of vagina, no extension to pelvic wall. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIIA includes: T3a, N0, M0. T3a: Tumor involves serosa and/or adnexa (direct extension or metastasis). N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IIIA includes: T3a, N0, M0. T3a: Microscopic peritoneal metastasis outside the pelvis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: (T4a, N1, M0); (T3, N2, M0); (T2, N3, M0). T2: Tumor invades the muscularis propria. T3: Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures. T4a: Tumor invades serosa (visceral peritoneum). N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: T3a, N0, M0. T3a: Multiple tumors more than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Ovarian cancer with positive retroperitoneal lymph nodes and/or microscopic metastasis beyond the pelvis. (FIGO, 2014)
Stage IIIA includes: T3a, N0, M0. T3a: Microscopic peritoneal metastasis beyond pelvis (no macroscopic tumor). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIIB includes: (T3b, Any N, M0); (T1-3, N1, M0). T3: Tumor extends to pelvic wall and/or involves lower third of vagina, and/or causes hydronephrosis or non-functioning kidney. T3b: Tumor extends to pelvic wall and/or causes hydronephrosis or non-functioning kidney. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIIB includes: T3b, N0, M0. T3b: Tumor involves vagina (direct extension or metastasis) or parametrial tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Macroscopic peritoneal metastasis outside the pelvis 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: (T4b, N0, M0); (T4b, N1, M0); (T4a, N2, M0); (T3, N3, M0). T3: Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures. T4a: Tumor invades serosa (visceral peritoneum). T4b: Tumor invades adjacent structures. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIIB small cell lung carcinoma that has spread to the pleural fluid.
Stage IIIB small cell lung carcinoma that has not spread to the pleural fluid.
Stage IIIC includes: IIIC1 (T1-T3, N1, M0); IIIC2 (T1-T3, N2, M0). T1: Tumor confined to corpus uteri. T2: Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus. Endocervical glandular involvement only should be considered as Stage I and not as Stage II. T3: Tumor involves serosa and/or adnexa, vagina, or parametrial tissue. N1: Regional lymph node metastasis to pelvic lymph nodes. N2: Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IIIC includes: (T3c, N0, M0); (Any T, N1, M0). T3c: Peritoneal metastasis outside the pelvis and more than 2 cm in diameter. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Ovarian cancer with macroscopic, extrapelvic, peritoneal metastasis greater than 2 cm +/- positive retroperitoneal lymph nodes. Includes extension to capsule of liver/spleen. (FIGO, 2014)
Stage IIIC includes: (T3c, N0, M0); (Any T, N1, M0). T3c: Peritoneal metastasis beyond pelvis more than 2cm in greatest dimension and/or regional lymph node metastasis. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage III includes: IIIA (T1, N1, M0); (T2, N1, M0); (T3, N1, M0); (T4, N0, M0); IIIB (T4, N1, M0); (Any T, N2, M0); (Any T, N3, M0). T1: Tumor 2 cm or less in greatest dimension. T2: tumor more than 2 cm but not more than 5 cm in greatest dimension. T3: Tumor more than 5 cm in greatest dimension. T4: Tumor of any size that invades adjacent organ(s). N1: Metastasis in perirectal lymph node(s). N0: No regional lymph node metastasis. N2: Metastasis in unilateral internal iliac and/or inguinal lymph node(s). N3: Metastasis in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage III includes: T4, Any N, M0. T4: Tumor invades peripancreatic soft tissues or other adjacent organs or structures other than the pancreas. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage III includes: T3, N0, M0, G3, G4. T3: Tumor more than 8 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G3: Poorly differentiated. G4: Undifferentiated. (AJCC 7th ed.)
Stage III includes: IIIA: (T3, N0, M0); IIIB: (T4, N0, M0); IIIC: (Any T, Any N, M0). IIIA: T3: Multiple tumors more than 5 cm or tumor involving a major branch of the portal or hepatic vein(s). T4: Tumors(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor more than 4 cm in greatest dimension or with fixation of hemilarynx. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 6th ed.)
Stage III carcinoma of the liver according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. T1: Tumor restricted to any one subsite, with or without bony invasion. T2: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Unresectable unilateral tumor infiltrating across the midline, with or without regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration (unresectable) or by lymph node involvement. The midline is defined as the vertebral column. Tumors originating on one side and crossing the midline must infiltrate to or beyond the opposite side of the vertebral column. (cancer.gov)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Maxillary sinus: Tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. Ethmoid sinus: Tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage III includes: (T1, T2, N1, M0); (T1, T2, N2, M0); (T3, N0, N1, N2, M0). T1: Pleural mesothelioma with a tumor limited to the ipsilateral parietal pleura with or without mediastinal pleura and with or without diaphragmatic pleural involvement. T2: Pleural mesothelioma with a tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following: involvement of diaphragmatic muscle; extension of tumor from visceral pleura into the underlying pulmonary parenchyma. T3: Pleural mesothelioma with a locally advanced but potentially respectable tumor. Tumor involving all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following: involvement of the endothoracic fascia; extension into the mediastinal fat; solitary, completely respectable focus of tumor extending into the soft tissues of the chest wall; nontransmural involvement of the pericardium. N0: No regional lymph node metastasis. N1: Pleural mesothelioma with metastases in the ipsilateral bronchopulmonary or hilar lymph nodes. N2: Pleural mesothelioma with metastases in the subcarinal or the ipsilateral mediastinal lymph nodes including the ipsilateral internal mammary and peridiaphragmatic nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: T3, N0, M0. T3: Tumor invades beyond muscularis into peripelvic fat or the renal parenchyma. N0: No lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: T3, N0, M0. T3: For renal pelvis only: tumor invades beyond muscularis into peripelvic fat or the renal parenchyma. For ureter only: tumor invades beyond muscularis into periureteric fat. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor with invasion of maxilla, mandible, orbit, or temporal bone. T1: Tumor 2 cm or less in greatest dimension with less than two high-risk features. T2: Tumor size greater than 2 cm in greatest dimension or tumor of any size with two or more high-risk features. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. M0: No clinical or radiographic evidence of distant metastasis. (AJCC 7th Ed.)
Stage III includes: (T1, N1a, M0); (T2, N1a, M0); (T3, N1a, M0). T1: Tumor size 2 cm or less in greatest dimension, limited to the thyroid gland. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid gland. T3: Tumor more than 4 cm in greatest dimension and limited to the thyroid gland, or tumor of any size with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues). N1a: Metastasis to pretracheal, paratracheal or prelaryngeal/Delphian lymph nodes (Level VI lymph nodes). M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: T3, N0, M0. T3: Tumor invades beyond muscularis into periureteric fat. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, N0, M0), (T3, N1, M0). T1: Tumor invades subepithelial connective tissue. T2: Tumor invades any of the following: corpus spongiosum, prostate, periurethral muscle. T3: Tumor invades any of the following: corpus cavernosum, beyond prostatic capsule, anterior vagina, bladder neck. N1: Metastasis in a single lymph node 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: IIIA (T2c-d, N0, M0); (T3b-c, N0, M0); (T4a, N0, M0); IIIB (T3d, N0, M0); (T4b-c, N0, M0); IIIC (T4d-e, N0, M0). T2c: Ciliary body and choroid: Tumor size category 2 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. T2d: Ciliary body and choroid: Tumor size category 2 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. T3b: Ciliary body and choroid: Tumor size category 3 with ciliary body involvement. T3c: Ciliary body and choroid: Tumor size category 3 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. T4a: Iris: Tumor with extrascleral extension less than or equal to 5 mm in diameter. Ciliary body and choroid: Tumor size category 4 without ciliary body involvement and extraocular extension. T3d: Ciliary body and choroid: Tumor size category 3 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. T4b: Iris: Tumor with extrascleral extension more than 5 mm in diameter. Ciliary body and choroid: Tumor size category 4 with ciliary body involvement. T4c: Ciliary body and choroid: Tumor size category 4 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. T4d: Ciliary body and choroid: Tumor size category 4 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. T4e: Ciliary body and choroid: Any tumor size category with extraocular extension more than 5 mm in diameter. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: (T2, N0, M0); (T3,N0, M0). T2: Tumor more than 2 cm but not more than 5 cm in greatest dimension. T3: Tumor more than 5 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage II includes: IIA (T3, N0, M0); IIB (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor invades the pancreas. T1: Tumor limited to ampulla of Vater or sphincter of Oddi. T2: Tumor invades the duodenal wall. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage II includes: IIA (T1, N0, M0, G3, G4); IIB (T2, N0, M0, G3, G4). T1: Tumor 8 cm or less in greatest dimension. T2: Tumor more than 8 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G3: Poorly differentiated. G4: Undifferentiated. (AJCC 7th ed.)
Stage II carcinoma of the liver according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage II includes: T2, N0, M0. T2: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage 2 includes stage 2A and stage 2B. Stage 2A: Localized tumor with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumor microscopically. Stage 2B: Localized tumor with or without complete gross excision, with ipsilateral nonadherent lymph nodes positive for tumor. Enlarged contralateral lymph nodes must be negative microscopically. (cancer.gov)
Stage II includes: T2, N0, M0. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage II includes: T2, N0, M0. T2: Pleural mesothelioma with a tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following: involvement of diaphragmatic muscle; extension of tumor from visceral pleura into the underlying pulmonary parenchyma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor invades muscularis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor invades the muscularis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor size greater than 2 cm in greatest dimension or tumor of any size with two or more high-risk features. High-risk features for the primary tumor staging are defined as follows: depth/invasion of more than 2 mm thickness; Clark level equal or greater than IV; and perineural invasion. Anatomic location: primary site ear and primary site non-hair-bearing lip. Differentiation: poorly differentiated or undifferentiated. N0: No regional lymph node metastasis. M0: No clinical or radiographic evidence of distant metastasis. (AJCC 7th ed.)
Stage II includes: IIA (T1a, N0, M0, G2, G3); (T1b, N0, M0, G2, G3); IIB (T2a, N0, M0, G2); (T2b, N0, M0, G2). T1a: Superficial tumor 5 cm or less in greatest dimension. T1b: Deep tumor 5 cm or less in greatest dimension. T2a: Superficial tumor more than 5 cm in greatest dimension. T2b: Deep tumor more than 5 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G2: Grade 2. G3: Grade 3. (AJCC 7th ed.)
Ann Arbor Classification: Stage II: Involvement of two or more lymph node regions on the superior side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph node(s) with or without involvement of other lymph node regions on the same side of the diaphragm (IIE). Note: The number of lymph node regions involved may be indicated by a subscript.
Stage II includes: (T2, N0, M0); (T3, N0, M0). T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid gland. T3: Tumor more than 4 cm in greatest dimension and limited to the thyroid gland, or tumor of any size with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor invades any of the following: corpus spongiosum, prostate, periurethral muscle. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: IIA (T1b-d, N0, M0); (T2a, N0, M0); IIB (T2b, N0, M0); (T3a, N0, M0). T1b: Iris: Tumor limited to the iris more than 3 clock hours in size. Ciliary body and choroid: Tumor size category 1 with ciliary body involvement. T1c: Iris: Tumor limited to the iris with secondary glaucoma. Ciliary body and choroid: Tumor size category 1 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. T1d: Ciliary body and choroid: Tumor size category 1 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. T2a: Iris: Tumor confluent with or extending into the ciliary body, choroid, or both, with secondary glaucoma. Ciliary body and choroid: Tumor size category 2 without ciliary body involvement and extraocular extension. T2b: Ciliary body and choroid: Tumor size category 2 with ciliary body involvement. T3a: Iris: Tumor confluent with or extending into the ciliary body, choroid, or both, with sclera extension and secondary glaucoma. Ciliary body and choroid: Tumor size category 3 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes T4b, NO,MO/any T NI, MO/ any T N2 MO,/ any T N3 MO/ any T any N M1 : T4b: Tumor invades the pelvic wall, abdominal wall. N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension. N2: Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension. N3: Metastasis in a lymph node more than 5 cm in greatest dimension. M1: Distant metastasis.
Stage IVA includes: Any T, N0, M1a, Any G. N0: No regional lymph node metastasis. M1a: Distant metastasis to lung. (AJCC 7th ed.)
Stage IVA includes: T4, Any N, M0. T4: Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4). M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IVA includes: Any T, N1, M0. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Tumor with moderately advanced local disease. Tumor invades the thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue. Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. T1: Tumor limited to one subsite of hypopharynx and/or 2 cm or less in greatest dimension. T2: Tumor invades more than one subsite of the hypopharynx or an adjacent site, or measures more than 2 cm but not more than 4 cm in greatest diameter without fixation of hemilarynx. T3: Tumor measuring more than 4 cm in greatest dimension or tumor with fixation of hemilarynx or extension to esophagus. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Tumor with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); T4a: Supraglottis: Moderately advanced local disease. Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). Glottis: Moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). Subglottis: Moderately advanced local disease. Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Lip cancer with moderately advanced local disease. Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose. T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension. T3: Tumor more than 4 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Moderately advanced disease. Tumor invades skin, mandible, ear canal, and/or facial nerve. T1: Tumor measuring 2 cm or less in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. T2: Tumor measuring more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. T3: Tumor measuring more than 4 cm in greatest dimension, and/or tumor having extraparenchymal extension. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0). T4: Nasopharyngeal cancer with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit, or with extension to the infratemporal fossa/masticator space. N0: No regional lymph node metastasis. N1: Nasopharyngeal cancer with unilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral, retropharyngeal lymph nodes, 6 cm or less in greatest dimension. Midline nodes are considered ipsilateral nodes. N2: Nasopharyngeal cancer with bilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa. Midline nodes are considered ipsilateral nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Oral cavity cancer with moderately advanced local disease. Tumor invades adjacent structures only (e.g., through cortical bone [mandible or maxilla] into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face). T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension. T3: Tumor more than 4 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Tumor with moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of larynx. T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension. T3: Tumor measuring more than 4 centimeters in greatest dimension or extension to lingual surface of epiglottis. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Tumor with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); T4a: Maxillary sinus: Moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. Ethmoid sinus: Moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. T3: Maxillary sinus: Tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. Ethmoid sinus: Tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA carcinoma of the pharynx according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage IVA includes: IVA (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4, Any N, M0). N2: Bilateral regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage IVB includes: (Any T, N1, Any M, Any G); (Any T, Any N, M1b, Any G). N1: Regional lymph node metastasis. M1b: Metastasis to other distant sites. (AJCC 7th ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, or lung, liver, or bone. It excludes metastasis to para-aortic lymph nodes, vagina, pelvic serosa, or adnexa). This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis. (AJCC 7th ed.)
Stage IVB includes: (T4b, Any N, M0); (Any T, N3, M0). T4b: Tumor with very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: (T4b, Any N, M0); (Any T, N3, M0). T4b: Supraglottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. Glottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. Subglottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB carcinoma of the liver according to the American Joint Committee on Cancer, 7th and 8th editions.
Stage IVB includes: (T4b, Any N, M0); (Any T, N3, M0). T4b: Very advanced disease. Tumor invades skull base and/or pterygoid plates and/or encases carotid artery. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: Any T, N3, M0. N3: Nasopharyngeal cancer with metastasis in a lymph node (s) more than 6 cm in greatest dimension and/or to supraclavicular fossa. Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described by Ho. It is defined by three points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, (3) the point where the neck meets the shoulder. This would include caudal portions of levels IV and VB. All cases with lymph nodes (whole or part) in the fossa are considered N3b. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: (Any T, N3, M0); (T4b, Any N, M0). T4b: Oral cavity cancer with very advanced local disease. Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: (T4b, Any N, M0); (Any T, N3, M0). T4b: Tumor with very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery. N3: Tumor with metastasis in a lymph node more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: (T4b, Any N, M0); (Any T, N3, M0). T4b: Very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve, nasopharynx, or clivus. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB carcinoma of the pharynx according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage IVC includes: Any T, Any N, M1. M1: Distant metastasis. (AJCC 7th ed.)
Stage IVC carcinoma of the pharynx according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage IV includes: (Any T, Any N, M1). M1: Distant metastasis. (AJCC 6th and 7th Eds.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 7th Ed.)
Stage IV includes: IVA (Any T, N0, M1a, Any G); IVB (Any T, N1, Any M, Any G); (Any T, Any N, M1b, Any G). N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M1a: Distant metastasis to lung. M1b: Metastasis to other distant sites. (AJCC 7th ed.)
Stage IV includes (Any T, Any N, M1). M1: Distant metastasis. (AJCC 6th ed.) - 2003
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB (T4b, Any N, M0); (Any T, N3, M0); IVC (Any T, Any N, M1). T4a: Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophagus, or central compartment soft tissue. T4b: Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. N2: Metastasis in a single ipsilateral lymph node, more than 3cm but not more than 6cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in greatest dimension. N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M1: Distant metastasis. (AJCC 6th ed.)
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0);. IVB (Any T, N3, M0); (T4b, Any N, M0); IVC (Any T, Any N, M1). T4a (lip): Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose. T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in dimension. N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M1: Distant metastasis. (AJCC 6th and 7th eds.)
Stage IV carcinoma of the liver according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage IV carcinoma of the major salivary glands with regional lymph nodes and/or distant metastases.
Stage IV carcinoma of the major salivary glands without regional lymph nodes or distant metastases.
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (T4b, Any N, M0); (Any T, N3, M0); IVC: (Any T, Any N, M1). T4a: Moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. T4b: Very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve, nasopharynx, or clivus. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (T4b, Any N, M0); (Any T, N3, M0); IVC: (Any T, Any N, M1). T4a: Maxillary sinus: Moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. Ethmoid sinus: Moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. T4b: Very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve, nasopharynx, or clivus. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage IV includes: (T4, Any N, M0); (Any T, N3, M0); (Any T, Any N, M1). T4: Pleural mesothelioma with a locally advanced technically unresectable tumor. Tumor involving all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following: diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction; direct transdiaphragmatic extension of tumor to the peritoneum; direct extension of tumor to the contralateral pleura; direct extension of tumor to mediastinal organs; direct extension of tumor into the spine; tumor extending through to the internal surface of the pericardium with or without a pericardial effusion or tumor involving the myocardium. N3: Pleural mesothelioma with metastases in the contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral supraclavicular lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage IV includes: (T4, N0, M0); (Any T, N1, M0); (Any T, N2, M0); (Any T, N3, M0); (Any T, Any N, M1). T4: Tumor invades adjacent organs, or through the kidney into perinephric fat. N0: No regional lymph node metastasis. N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension. N2: Metastasis in a single lymph node, more than 2 cm but not more than 5cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension. N3: Metastasis in a lymph node, more than 5 cm in greatest dimension. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage IV includes: (T4, N0, M0); (Any T, N1, M0); (Any T, N2, M0); (Any T, N3, M0); (Any T, Any N, M1). T4: Tumor invades adjacent organs, or through the kidney into the perinephric fat. N0: No regional lymph node metastasis. N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension. N2: Metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension. N3: Metastasis in a lymph node, more than 5 cm in greatest dimension. M0: No distant metastasis. N1: Distant metastasis. (AJCC 7th ed.)
Stage IV includes: (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T Any, N3, M0); (T4, N Any, M0); (T Any, N Any, M1). T1: Tumor 2 cm or less in greatest dimension with less than two high-risk features. T2: Tumor size greater than 2 cm in greatest dimension or tumor of any size with two or more high-risk features. T3: Tumor with invasion of maxilla, mandible, orbit, or temporal bone. T4: Tumor with invasion of skeleton or perineural invasion of skull base. N0: No regional lymph node metastasis. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M1: Distant metastases. (AJCC 7th Ed.)
Stage IV includes: (T4, N0, M0); (T4, N1, M0); (Any T, N2, M0), (Any T, Any N, M1). T4: Tumor invades other adjacent organs. N0: No regional lymph node metastasis. N1: Metastasis in a single lymph node 2 cm or less in greatest dimension. N2: Metastasis in a single lymph node more than 2 cm in greatest dimension, or in multiple lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage IV includes: (Any T, N1, M0); (Any T, Any N, M1a-c). N1: Regional lymph node metastasis. M1a: Distant metastasis, with the largest diameter of the largest metastasis measuring 3 cm or less. M1b: Distant metastasis, with the largest diameter of the largest metastasis measuring 3.1-8.0 cm. M1c: Distant metastasis, with the largest diameter of the largest metastasis measuring 8.0 cm or more. (AJCC 7th ed.)
Stage IV includes: IVA: (T4, Any N, M0) and IVB: (Any T, Any N, M1). T4: Tumor invades mucosa of the bladder or rectum and/or extends beyond the true pelvis (bullous edema is not sufficient evidence to classify tumor as T4). M0: No distant metastasis. M1: Distant metastasis. (AJCC 6th and 7th eds.)
Stage I includes: IA (T1, N0, M0); IB (T2, N0, M0). T1: Tumor limited to ampulla of Vater or sphincter of Oddi. T2: Tumor invades duodenal wall. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage I includes: IA (T1, N0, M0, G1, G2, GX); IB (T2, N0, M0, G1, G2, GX); (T3, N0, M0, G1, G2, GX). T1: Tumor 8 cm or less in greatest dimension. T2: Tumor more than 8 cm in greatest dimension. T3: Discontinuous tumors in the primary bone site. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated-low grade. G2: Moderately differentiated-low grade. GX: Grade cannot be assessed. (AJCC 7th ed.)
Stage I carcinoma of the liver according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage I includes: T1, N0, M0. T1:Tumor restricted to any one subsite, with or without bony invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Localized tumor with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumor microscopically. (cancer.gov)
Stage I includes: T1, N0, M0. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage I includes: (T1, N0, M0); IA: (T1a, N0, M0); IB: (T1b, N0, M0). T1: Pleural mesothelioma with a tumor limited to the ipsilateral parietal pleura with or without mediastinal pleura and with or without diaphragmatic pleural involvement. T1a: Pleural mesothelioma with no involvement of the visceral pleura. T1b: Pleural mesothelioma with a tumor also involving the visceral pleura N0: No regional lymph metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage I includes: T1, M0, M0. T1: Tumor invades subepithelial connective tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage I includes: T1, N0, M0. T1: Tumor invades subepithelial connective tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage I includes: T1, N0, M0. T1: Tumor 2 cm or less in greatest dimension with less than two high-risk features. High-risk features for the primary tumor staging are defined as follows: depth/invasion of more than 2 mm thickness, Clark level equal or greater than IV, and perineural invasion. Anatomic location: primary site ear and primary site non-hair-bearing lip. Differentiation: poorly differentiated or undifferentiated. N0: No regional lymph node metastasis. M0: No clinical or radiographic evidence of distant metastasis. (AJCC 7th ed.)
Stage I includes: IA (T1a, N0, M0, G1, GX); (T1b, N0, M0, G1, GX); IB (T2a, N0, M0, G1, GX); (T2b, N0, M0, G1, GX). T1a: Superficial tumor 5 cm or less in greatest dimension. T1b: Deep tumor 5 cm or less in greatest dimension. T2a: Superficial tumor more than 5 cm in greatest dimension. T2b: Deep tumor more than 5 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Grade 1. GX: Grade cannot be assessed. (AJCC 7th ed.)
Stage I includes: T1, N0, M0. T1: Tumor size 2 cm or less in greatest dimension, limited to the thyroid gland. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage I includes: T1a, N0, M0. T1a: Iris: Tumor limited to the iris not more than 3 clock hours in size. Ciliary body and choroid: Tumor size category 1 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
An uncommon benign cartilaginous neoplasm arising from the sternum. It is characterized by the presence of spindle-shaped or stellate chondrocytes, a lobulated growth pattern, myxoid stroma formation, and sometimes multinucleated giant cells.
A non-neoplastic or neoplastic disorder that affects the sternum.
A rare schwannoma that arises from the sternum.
A rare lymphoma that arises from the bone or soft tissue of the sternum.
A neoplastic process characterized by a diffuse poorly circumscribed overgrowth of adipose tissue in the face, upper middle back, and sternal region. It is associated with adrenocortical steroid therapy or an increase in endogenous adrenocortical hormone.
A term referring to the presence of tumor emboli or tumor masses within the stroma of an organ.
A hemangioma arising from the subglottic area.
An adenocarcinoma that arises from the sublingual gland.
An adenocarcinoma with serous acinar cell differentiation that arises from the submandibular gland.
An adenocarcinoma that arises from the submandibular gland. Representative examples include polymorphic low-grade adenocarcinoma and acinic cell carcinoma.
An aggressive carcinoma that arises from the submandibular gland. It is characterized by the presence of malignant epithelial and myoepithelial cells forming cribriform, tubular, and solid patterns. It usually presents as a slow growing mass. Patients develop pain because of the tendency of these carcinomas to invade perineural tissues.
A carcinoma that arises from a pleomorphic adenoma in the submandibular gland. Patients usually present with a history of a long-standing tumor mass which grew rapidly in the past few months. Patients with non-invasive or minimally invasive carcinoma have an excellent prognosis. In cases where there is invasion of the surrounding tissues, the clinical course is aggressive.
A carcinoma that arises from the submandibular gland. It usually presents as a firm and painless mass. It is characterized by the presence of epidermoid cells, mucus producing cells, and cells of intermediate type. The majority of cases have a favorable outcome.
An invasive squamous cell carcinoma that arises from the submandibular gland. It usually affects elderly patients and presents as a rapidly enlarging tumor mass, often associated with pain.
A carcinoma that arises from the submandibular gland and is characterized by the presence of undifferentiated, anaplastic malignant epithelial cells.
A term used by urologists to describe an infiltrating carcinoma of the bladder that has not invaded into the muscularis propria of the bladder wall regardless of histologic type or grade.
A lesion with limited invasion of deeper tissues.
A carcinoma originating from the apical lung. Most superior sulcus lung carcinomas are bronchogenic carcinomas. This carcinoma may be associated with Pancoast syndrome. lt is also known as Pancoast tumor.
A malignant vascular neoplasm arising from the superior vena cava.
An aggressive malignant smooth muscle neoplasm, arising from the superior vena cava. It is characterized by a proliferation of neoplastic spindle cells.
Blockage of blood flow through the superior vena cava (SVC). Because the venous drainage from the upper extremities, upper thorax and head is obstructed, SVC obstruction presents with symptoms related to engorgement of these areas. Both the degree of SVC compromise and the extent of collateral veins determine the varied clinical presentation, which can be as mild as slight facial and upper extremity edema or as dire as intracranial swelling, seizures, hemodynamic instability and tracheal obstruction.
A meningioma that affects the suprasellar region.
A meningioma that affects the supratentorial brain.
A central nervous system embryonal tumor, not otherwise specified arising from the supratentorial region.
A benign tumor derived from schwann cells of the peripheral sympathetic nervous system, including the sympathetic plexus.
A bone osteosarcoma affecting multiple skeletal sites, with multifocal lesions discovered within 6 months of the appearance of the initial tumor. It has a poor prognosis.
A rare hemangioma arising from synovium lining surfaces.
An anaplastic large cell lymphoma that is not confined to a single anatomic site and involves multiple nodal and/or extranodal sites.
A T-cell lymphoproliferative disorder with uncertain malignant potential. A representative example is lymphomatoid papulosis.
A T-cell prolymphocytic leukemia characterized by the presence of neoplastic prolymphocytes with irregular or cerebriform nuclear outline.
A T-cell prolymphocytic leukemia characterized by the presence of small neoplastic prolymphocytes often with invisible nucleolus by light microscopy.
A morphologic variant of papillary carcinoma of the thyroid gland characterized by the presence of tall malignant follicular cells, arranged in papillary and trabecular patterns. Necrotic changes and high mitotic activity are present.
A glomus tumor characterized by huge vascular channel formations.
A benign tumor, composed of mature adipocytes, that arises within the tendon sheath.
A central nervous system teratoma characterized by the presence of a malignant component. The malignant component most often is sarcomatous (rhabdomyosarcoma or undifferentiated sarcoma) or carcinomatous (squamous cell carcinoma or adenocarcinoma).
A carcinoid tumor that arises from the testis. It usually presents as a testicular mass without the symptoms of carcinoid syndrome.
A mature teratoma that arises from the testis and is characterized by the presence of one or more cysts. The cysts are lined by squamous epithelium and contain skin appendages. Other teratomatous components may or may not be present.
A germ cell tumor arising from the testis. Representative examples include teratoma, seminoma, embryonal carcinoma, and yolk sac tumor.
A rare sex cord-stromal tumor that arises from the testis. It is characterized by the presence of granulosa-like cells and Call-Exner bodies. There are two variants described, the adult and the juvenile.
A malignant neoplasm that arises from the testis and is characterized by the presence of large germ cells with abundant cytoplasm in the seminiferous tubules, associated with an invasive germ cell tumor in the adjacent tissues.
A myeloid or more commonly lymphoid leukemia (acute or chronic) affecting the testis. Microscopically, there is interstitial infiltration of the testis by leukemic cells. Acute lymphoblastic leukemia with testicular involvement is not uncommon in boys. Sometimes (up to 10% of the cases), testicular involvement may be the initial manifestation of relapsed acute lymphoblastic leukemia. --03
A malignant mixed germ cell tumor that arises from the testis and is characterized by the presence of choriocarcinoma and embryonal carcinoma morphologic components.
A malignant germ cell tumor arising from the testis. It is characterized by a mixture of choriocarcinoma and seminomatous morphologic elements. Patients may present with painless or painful testicular swelling.
A malignant mixed germ cell tumor arising from the testis. It is characterized by the presence of a teratomatous component and malignant syncytiotrophoblastic cells.
A malignant mixed germ cell tumor arising from the testis. It is characterized by the presence of a mixture of embryonal carcinoma and a seminomatous component.
A malignant mixed germ cell tumor arising from the testis, characterized by the presence of an embryonal carcinomatous component and a teratomatous component.
A malignant mixed germ cell tumor arising from the testis. It is characterized by the presence of a mixture of embryonal carcinoma, a teratomatous component, and a seminomatous component.
A malignant non-seminomatous germ cell tumor arising from the testis. It is characterized by a mixture of embryonal carcinoma and yolk sac morphologic elements. Patients may present with painless or painful testicular swelling.
A testicular mixed germ cell-sex cord-stromal tumor in which the neoplastic germ cells and the neoplastic sex cord-stromal cells do not form nests and are instead arranged in a diffuse pattern.
A malignant germ cell tumor that arises from the testis and is characterized by the presence of more than one histologic component. Representative examples include mixed choriocarcinoma and embryonal carcinoma, mixed embryonal carcinoma and seminoma, and mixed yolk sac tumor and teratoma.
A malignant non-seminomatous germ cell tumor arising from the testis. It is characterized by a mixture of yolk sac and teratomatous morphologic elements. Patients may present with painless or painful testicular swelling.
A malignant germ cell tumor arising from the testis. It is characterized by a mixture of yolk sac, teratomatous, and seminomatous morphologic elements. Patients may present with painless or painful testicular swelling.
A non-neoplastic disorder that affects the testis. Representative examples include infection, torsion, and infarction.
A testicular germ cell tumor characterized by the absence of a seminomatous component. It includes embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, and mixed forms.
A malignant mesenchymal tumor with skeletal muscle differentiation affecting the testis.
A sarcoma that arises from the testis. The majority of cases arise from teratomas or spermatocytic seminomas.
This is a new term included in the 2003 edition of the WHO classification of testicular tumors. Previously, testicular teratomas were classified as mature, immature, and ""with malignant transformation"". WHO '03 reorganizes the classification into two categories: teratoma and teratoma with somatic-type malignancy (possibly ""non-germ cell malignancy""). It is clear by now that teratomas (both mature and immature) in postpubertal patients can be associated with metastases. In contrast, teratomas (both mature and immature) in prepubertal patients are always benign (from the 2003 International Society of Urological Pathology companion meeting syllabus-annual meeting of the United States and Canadian Academy of Pathology).--2002
A group of neoplasms that arise from the ovary and represent a spectrum of tumors ranging from neoplasms that are composed entirely of fibroblasts to those that are composed predominantly of theca cells.
An acute myeloid leukemia arising as a result of the mutagenic effect of chemotherapy agents and/or ionizing radiation. (WHO, 2001)
A meningioma that arises from the meninges of the thoracic region of the spinal cord.
Exposure to thorotrast, which contains particles of the radioactive compound thorium dioxide, as a radiocontrast agent. It is a carcinogenic compound, linked to the development of bile duct cancer, leukemia, and angiosarcoma.
A process that involves either a blood clot or bleeding, such as a heart attack or stroke.
A rare primary thymic carcinoma, characterized by the presence of carcinoma cells with glandular differentiation.
A well-circumscribed tumor of the thymus composed of islands of normal thymic parenchyma and mature adipose tissue. It is not clear if thymolipoma is a neoplastic or non-neoplastic lesion.
A lymphoma that arises from the thymus. Representative examples include mediastinal (thymic) large B-cell lymphoma and Hodgkin lymphoma.
A primary thymic neuroendocrine tumor, often associated with Cushing syndrome. Two morphologic subtypes are recognized: typical and atypical carcinoid tumors. Atypical carcinoid tumors have a more aggressive clinical course.
A usually aggressive malignant vascular tumor primarily involving the thyroid gland. It is often associated with longstanding nodular goiter.
A diffuse large B-cell lymphoma primarily involving the thyroid gland.
A kind of thyroid adenoma characterized by the presence of oxyphil cells.
A rare, circumscribed or encapsulated tumor arising from the follicular cells of the thyroid gland. It is characterized by a trabecular growth pattern and hyalinized stroma formation. The vast majority of cases have a benign clinical course.
A diffuse large B-cell lymphoma variant, primarily involving the thyroid gland. It is composed predominantly of immunoblasts.
A lymphoma primarily involving the thyroid gland.
An extranodal marginal zone B-cell lymphoma arising from mucosa-associated lymphoid tissue in the thyroid gland. The vast majority of cases are associated with chronic lymphocytic thyroiditis.
A non-Hodgkin lymphoma primarily involving the thyroid gland. The vast majority of cases are either mucosa-associated lymphoid tissue lymphomas or diffuse large B-cell lymphomas.
A malignant soft tissue neoplasm primarily involving the thyroid gland.
A benign adipose tissue neoplasm of the tonsils.
A primary lymphoma that affects the tonsil and the bulk of the tumor is in this anatomic area. The majority of cases are B-cell non-Hodgkin lymphomas.
A non-keratinizing carcinoma arising from the tonsil. It is characterized by the presence of large malignant cells with vesicular nuclei, prominent nucleoli, syncytial growth pattern, and a lymphoplasmacytic infiltrate.
Acute myeloid leukemias arising as a result of the mutagenic effect of therapeutic agents targeting DNA-topoisomerase II. The vast majority of patients present without a preceding myelodysplastic phase. The acute myeloid leukemias are usually of the monoblastic or myelomonocytic type. Clonal cytogenetic abnormalities are frequently present and usually involve chromosome 11q23 (MLL gene).
A microscopic finding indicating that the neoplastic cells are arranged in trabeculae in a tumor sample.
A benign smooth muscle neoplasm arising from the trachea. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A rare lymphoma that arises from the trachea. Signs and symptoms include dyspnea, cough, wheezing, and stridor.
A rare malignant soft tissue neoplasm that arises from the trachea.
A hepatocellular carcinoma that develops following renal transplantation.
A Kaposi sarcoma that develops after organ transplantation.
A lung carcinoma in a patient with a history of organ transplantation.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the transverse colon. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A cutaneous myxoma arising from the hair follicle.
Infectious and parasitic diseases endemic in tropical and subtropical zones, including Chagas' disease, leishmaniasis, leprosy, malaria, onchocerciasis, schistosomiasis, sleeping sickness, yellow fever, and others; often water- or insect-borne.
An increase in gross volume and weight of the thymus gland, with maintenance of normal lobular architecture, and preservation of corticomedullary differentiation.
A meningioma that affects the tuberculum sellae.
A morphological appearance characteristic of neoplasms which arise from the glandular or ductal (or both) epithelium, consisting of glandular or ductal neoplastic proliferations forming small tubules with a lumen lined by neoplastic cells.
A morphologic finding that indicates the presence of cells undergoing necrosis within a tumor.
A papillary renal cell carcinoma characterized by the presence of papillae covered by small cells with scant amount of cytoplasm. The cells are arranged in a single layer on the basement membrane of the papillae.
A papillary renal cell carcinoma characterized by the presence of papillae covered by cells of a higher nuclear grade as compared to type 1 papillary renal cell carcinoma. The cells have eosinophilic cytoplasm and pseudostratified nuclei.
A variant of lymphomatoid papulosis characterized by the presence of scattered anaplastic large lymphocytes, often resembling Reed-Sternberg cells, admixed with acute and chronic inflammatory cells.
A variant of lymphomatoid papulosis characterized by an epidermotropic infiltrate composed of small atypical cerebriform-like lymphocytes.
The protrusion of contents of the abdominal cavity through the abdominal wall, at the site of the umbilicus, which results in obstruction, without mention of necrosis of the herniated contents.
A renal cell carcinoma characterized by morphologic features that do not fit easily into one of the other well-defined categories of renal cell carcinoma. Examples of such features include mixtures of morphologic patterns, mucin production, and sarcomatoid morphology.
A carcinoma without evidence of differentiation arising from the extrahepatic bile ducts.
An invasive carcinoma arising from the fallopian tube. It is characterized by the presence of a diffuse malignant infiltrate that is composed of epithelial cells without evidence of glandular or squamous differentiation.
A carcinoma that arises from the stomach and is characterized by the absence of microscopic features of glandular or squamous differentiation.
A carcinoma with poor prognosis that arises from the pancreas. It is characterized by the presence of a significant malignant component that does not show differentiation. The malignant cells represent a mixture of large, pleomorphic cells and giant cells, or adenocarcinoma cells and spindle cells, or spindle cells.
A carcinoma that arises from the parotid gland and is characterized by the presence of undifferentiated, anaplastic malignant epithelial cells.
An invasive prostate carcinoma without evidence of cellular differentiation.
An invasive malignant epithelial tumor that arises from the rectum. There is no morphologic, immunophenotypic, or molecular biological evidence of glandular or squamous differentiation.
A rare primary thymic carcinoma, characterized by an undifferentiated solid tumor growth, without associated sarcomatoid features.
An ovarian cyst that has a single compartment.
A malignant neoplasm which is not amenable to surgical resection.
A meningioma that affects the upper clivus.
A verrucous carcinoma of the oral cavity that arises from the upper gingiva.
A neoplasm of the ureter in which the epithelial cells grow downward into the underlying supportive tissue, which often causes hematuria.
A benign smooth muscle neoplasm arising from the ureter. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A benign nerve sheath tumor composed of Schwann cells, occurring in the ureter.
A rare carcinoma that arises from the ureter. It is characterized by the presence of small neuroendocrine cells. The prognosis is poor.
A rare squamous cell carcinoma that arises from the ureter.
A sexually transmitted papillary neoplasm that arises from the epithelial surface of the urethra, and caused by the human papillomavirus.
A benign polypoid lesion of mesodermal origin that arises from the urethra.
An adenocarcinoma that arises from the male or female urethra.
A morphologic variant of urethral adenocarcinoma characterized by the presence of tubulocystic or papillary structures lined with clear cuboidal or hobnail cells.
A neoplasm of the urethra in which the epithelial cells grow downward into the underlying supportive tissue.
A benign smooth muscle neoplasm arising from the urethra. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A metaplastic lesion of the urothelium found in the urethra. It is characterized by the presence of aggregates of cuboidal or hobnail cells and represents a reaction of the urothelium to injury caused by instrumentation, surgery or calculi.
A well differentiated, moderately differentiated, or poorly differentiated squamous cell carcinoma that arises from the male or female urethra.
A multinodular intermediate fibroblastic neoplasm arising from the bladder. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells.
A metaplastic lesion of the urothelium found in the urinary bladder. It is characterized by the presence of aggregates of cuboidal or hobnail cells and represents a reaction of the urothelium to injury caused by instrumentation, surgery or calculi.
An exophytic glandular neoplasm of the bladder, morphologically similar to its intestinal counterpart. It often coexists with in situ or infiltrating bladder adenocarcinoma.
A benign or malignant extra-adrenal paraganglioma that arises from the urinary system. The representative example is bladder paraganglioma.
Hyperplasia of the transitional epithelium of the urinary tract. Morphologically it is subdivided into flat and papillary hyperplasia. -- 2003
A malignant vascular neoplasm arising from the uterus.
A papilloma that arises from the squamous epithelium of the cervix.
A usually polypoid, benign neoplasm that arises from the endometrial cavity. It is characterized by the presence of a mesenchymal core component and an epithelial component that forms a lining on the mesenchymal core.
A benign mesothelial tumor of the serosal surface of the uterine body and myometrium. It is characterized by the presence of gland-like structures.
A usually polypoid, benign neoplasm that arises from the uterine corpus. It is characterized by the presence of benign epithelial glands embedded in benign fibromyomatous tissue.
An aggressive malignant tumor arising from trophoblastic cells in the uterus during pregnancy. Approximately half of the cases develop from a complete hydatidiform mole. There is often marked elevation of human chorionic gonadotropin (hCG) in the blood. Choriocarcinomas disseminate rapidly through the hematogenous route; the lungs are most frequently affected.
A primary endometrial adenocarcinoma composed of neoplastic cells that form complex glandular patterns associated with budding and branching of the neoplastic glands. The neoplastic glands resemble those of the normal endometrium and may or may not be associated with sheet-like proliferation of malignant cells. Endometrioid adenocarcinoma is the most commonly seen morphologic variant of endometrial adenocarcinoma.
An endometrioid adenocarcinoma arising from the endometrium, in which ciliated cells line the majority of the malignant glands.
An endometrioid adenocarcinoma arising from the endometrium. Morphologically it is characterized by the presence of malignant glandular cells containing glycogen vacuoles which are usually subnuclear and reminiscent of early secretory endometrium.
A morphologic variant of endometrioid adenocarcinoma characterized by the presence of large multinucleated clear cells.
A primary endometrioid adenocarcinoma of the endometrium characterized by the presence of spindled malignant epithelial cells.
A primary endometrioid adenocarcinoma of the endometrium characterized by the presence of a component with poorly differentiated carcinoma cells.
A primary endometrioid adenocarcinoma of the endometrium characterized by the presence of a component with undifferentiated malignant cells.
A primary polypoid malignant neoplasm of the uterine corpus characterized by the presence of a sarcomatous mesenchymal component and a benign epithelial component. Patients usually present with abnormal vaginal bleeding. It is considered a low grade malignant neoplasm and may recur following resection.
A non-neoplastic disorder that affects the uterine corpus. Representative examples include endometritis and uterine adenomyosis.
A non-neoplastic disorder that affects the uterine corpus or the cervix. Representative examples include endometritis, uterine adenomyosis, and cervicitis.
A high grade, aggressive adenocarcinoma arising from the endometrium. It is characterized by the presence of complex papillary patterns with cellular budding. Atypical mitoses, necrosis, and psammoma bodies may be present. It is classified as type II endometrial carcinoma and it is not associated with endometrial hyperplasia. It tends to invade deeply into the myometrium and spreads into the lymphatic vessels. Patients frequently present with spread of the tumor beyond the uterus at the time of diagnosis. The prognosis is usually poor.
A Kaposi sarcoma arising from the cervix in patients who are infected with the human immunodeficiency virus.
A Kaposi sarcoma arising from the stomach in patients who are infected with the human immunodeficiency virus.
A benign smooth muscle neoplasm arising from the vagina. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the vagina. It is characterized by a proliferation of neoplastic spindle cells.
A non-neoplastic disorder that affects the vagina. Representative examples include vaginal infection and vaginal fibroepithelial polyp.
A rare benign polypoid skeletal muscle neoplasm arising from the vagina. It is characterized by the presence of round striated muscle cells and strap-like skeletal muscle cells, and vascular space formations within a fibrous and myxoid stroma.
A benign papillary neoplasm that arises from the vagina and is characterized by the presence of a fibrovascular stalk lined by normal squamous epithelium. There is no evidence of atypia or relation to human papillomavirus.
A squamous cell carcinoma that arises from the vagina and is characterized by a papillary growth pattern, acanthotic epithelium with minimal or absent atypia, and pushing borders.
A rare yolk sac tumor that arises from the vagina.Patients present with abnormal vaginal bleeding or bloody discharge.
A benign, intermediate, or malignant vascular neoplasm that arises from the bone.
A benign or malignant vascular neoplasm that arises from the breast.
An aggressive malignant smooth muscle neoplasm, arising from the walls of the vascular system. It is characterized by a proliferation of neoplastic spindle cells.
The 20 kDa C-terminal domain of the vascular basement protein, Nidogen-1. It may have anti-angiogenic properties.
The protrusion of contents of the abdominal cavity through the abdominal wall, at the site of the linea alba, which results in obstruction, without mention of necrosis of the herniated contents.
A slow growing, locally recurring, very well differentiated papillary squamous cell carcinoma that arises from the penis. It is characterized by the presence of acanthosis and hyperkeratosis. The neoplastic infiltrate extends into the underlying stroma with a pushing border. Koilocytotic atypia is not present.
A morphologic architectural pattern in which the tumor cells spread vertically.
A primary endometrioid adenocarcinoma of the endometrium characterized by the presence of numerous finger-like villi lined by neoplastic columnar cells.
A morphological appearance resembling the villi seen on the mucosa of the small bowel
An astrocytoma that affects the optic tract. This condition can be seen in association with neurofibromatosis 1. It is most commonly seen in the pediatric age group.
A meningioma that affects the visual pathway.
A slow growing, locally infiltrating carcinoma that arises from the vulva. It is characterized by the presence of malignant cells that resemble the basal cells that are present in the epidermis.
A polypoid lesion that arises from the vulva and is characterized by the presence of fibrovascular stroma lined by squamous epithelium. There is no evidence of epithelial atypia.
A non-neoplastic disorder that affects the vulva. Representative examples include infection and fibroepithelial polyp.
A benign squamous neoplasm that arises from the vulva. It is characterized by the proliferation of the basal cells in the squamous epithelium, acanthosis, hyperkeratosis, and cysts formation.
A benign papillary neoplasm that arises from the vulva and is characterized by the presence of a delicate fibrovascular stalk lined by squamous epithelium. There is no evidence of epithelial atypia.
A highly differentiated squamous cell carcinoma that arises from the vulva. It is characterized by the presence of a warty and hyperkeratinized surface, malignant cells with abundant eosinophilic cytoplasm, minimal cytologic atypia, and absence or rarity of mitotic figures. The tumor infiltrates the underlying stroma with a pushing border.
A squamous cell carcinoma that arises from the penis. It is characterized by a papillary growth pattern, hyperkeratosis and parakeratosis. Koilocytotic atypia is present. Human papillomavirus types 16 and 6 have been identified in some cases.
A well differentiated extraskeletal myxoid chondrosarcoma.
A low or intermediate grade well differentiated tumor with neuroendocrine differentiation that arises from the pancreas. According to the presence or absence of clinical syndromes that result from hormone hypersecretion, pancreatic neuroendocrine tumors are classified either as functional or nonfunctional.
A localized or multifocal mesothelioma arising from the peritoneum and less often the pleura. Cases arising from the peritoneum predominantly occur in women. It is characterized by the formation of papillae, covered by a single layer of blunt mesothelial cells. Mitotic figures are not present. There is no evidence of severe cytologic atypia. It has a relatively favorable clinical outcome, compared to malignant mesothelioma.
An adenocarcinoma arising from the thyroid gland showing extensive evidence of follicular cell differentiation. According to the nuclear features of the malignant follicular cells, it is classified either as papillary, or follicular carcinoma.
A low-grade chondrosarcoma characterized by the presence of moderate cellularity, hyperchromatic and plump nuclei of uniform size, and occasional binucleated cells. Mitotic figures are absent.
A well-differentiated malignant neoplasm arising from the deep soft tissues. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
Grade I malignant smooth muscle neoplasm. It is characterized by a proliferation of neoplastic spindle cells.
A malignant hemangiopericytoma with well-differentiated morphological features.
An invasive prostate adenocarcinoma characterized by the presence of well differentiated malignant glandular epithelial components.
Cholecystitis that is characterized by nodules containing lipid.
A group of kidney carcinomas characterized by the presence of different translocations involving the chromosome Xp11.2. These translocations result in the creation of gene fusions involving the TFE3 gene. Patients are usually children and young adults. Morphologically, the malignant epithelial cells form papillary patterns.
A malignant germ cell tumor of the central nervous system composed of primitive-appearing epithelial cells - putatively representing yolk sac endoderm - set in a loose, variably cellular, and often conspicuously myxoid matrix, resembling extra-embryonic mesoblast. Eosinophilic hyaline globules immunoreactive for AFP are a diagnostic feature. (WHO)
A characteristic of a medicinal product, specifying that its most predominant agreeable savor detected by the unified sensation of taste and olfactory receptors resembles marshmallow.
A dietary supplement containing the levo-enantiomers of carnitine and tartrate with potential chemoprotective and antioxidant activities. L-carnitine L-tartrate increases fatty acid oxidation and reduces purine catabolism and free radical formation, which may prevent exercise fatigue, muscle weakness, chemotherapy-induced peripheral neuropathy, and hyperlipoproteinemia. L-carnitine, the biologically active form of carnitine, is a carrier molecule that transports activated long-chain fatty acids (LCFAs) from the cytosol to mitochondria where fatty acids are oxidized, resulting in ATP production. L-tartrate, a salt of tartaric acid, is a potent antioxidant.
The sodium salt of the S-isomer of omeprazole, with gastric proton pump inhibitor activity. In the acidic compartment of parietal cells, esomeprazole is protonated and converted into the active achiral sulfenamide; the active sulfenamide forms one or more covalent disulfide bonds with the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting its activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production. H+/K+ ATPase is an integral membrane protein of the gastric parietal cell.
The trisodium salt form of zinc diethylene triamine pentaacetate (Zn-DTPA or pentetate zinc) with chelating activity. Upon administration, Zn-DTPA loses the Zn ion to form stable chelates with metal ions because DTPA has a higher affinity for heavy metal ions than for Zn ions. Specifically, this agent is able to bind to and form strong complexes with the radioactive plutonium, americium, and cerium after internal contamination. The formation of these heavy metal chelates enhances radionuclide excretion.
Pre-clinical trials experiment conducted on the animal model with the goal to reduce cancer burden.
The sodium salt of bemiparin, a second generation, synthetic, low-molecular-weight heparin (LMWH) with anticoagulant activity. Derived, after depolymerisation and fractionation, from medical-grade porcine unfractionated heparin (UFH), bemiparin has an average molecular weight of 3,600 daltons and has a higher anti-factor Xa/anti-factor IIa ratio (8:1) than first-generation LMWHs. This anticoagulant binds to antithrombin III, thereby enhancing the inactivation of activated factor X (Factor Xa) and, to a lesser extent, activated factor II (Factor IIa). Compared to unfractionated heparins, the use of bemiparin is associated with lower incidences of major bleeding, osteoporosis, and heparin-induced thrombocytopenia. Bemiparin also promotes a greater release of tissue factor pathway inhibitor than UFH or dalteparin.
A whole phytocomplex concentrate (W.P.C.) composed of a standardized extract of the Cynara scolymus (artichoke) leaf with potential antioxidant, protective and chemopreventive activities. The artichoke W.P.C. is high in flavonoids and polyphenols, such as caffeoylquinic acids, which are mainly responsible for the pharmacological effects of the extract. Artichoke W.P.C. also contains protein, fiber, vitamins, minerals, numerous enzymes, volatile oils, phytosterols and polyunsaturated fatty acids.
The mesylate salt form of paroxetine, a phenylpiperidine derivative and a selective serotonin reuptake inhibitor (SSRI) with antidepressant and anxiolytic properties. Paroxetine binds to the pre-synaptic serotonin transporter complex resulting in negative allosteric modulation of the complex, thereby blocking reuptake of serotonin by the pre-synaptic transporter. Inhibition of serotonin recycling enhances serotonergic function through serotonin accumulation in the synaptic cleft, which resulting in long-term desensitization and downregulation of 5HT1 (serotonin) receptors and leading to symptomatic relief of depressive illness.
The oil extracted from the seeds of Apium graveolens. Celery seed oil is used to treat disorders of the digestive system.
The fruit of the hawthorn tree or bush. It has been used in some cultures to treat certain medical problems, including heart problems and gastrointestinal problems.
A methylene-substituted bisphosphonate. Medronic acid has affinity for and adheres to the surface of hydroxyapatite crystals in the bone matrix. This agent accumulates at sites of osteoid mineralization and can be used, complexed with radioisotopes such as technetium 99m, in bone imaging.
A dietary supplement consisting of bovine colostrum, containing high titers of immunoglobulins (Igs), with immunostimulating and anti-infective activities. Hyperimmune bovine colostrum is harvested during the first days after calving from cows that have been inoculated repeatedly with specific pathogens during pregnancy. In addition to high titers of anti-pathogen specific antibodies, hyperimmune colostrum is also rich in other immune factors, proline-rich polypeptides (PRP), lactoferrin, glycoproteins, lactalbumins, cytokines, growth factors, vitamins, and minerals. This dietary supplement may exhbit anti-infective activity in immunocompromised patients.
Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord comprising closely clustered, enlarged capillary channels (caverns) with a single layer of endothelium without mature vessel wall elements or normal intervening brain parenchyma. The diameter of CCMs ranges from a few millimeters to several centimeters. CCMs increase or decrease in size and increase in number over time. Hundreds of lesions may be identified, depending on the person's age and the quality and type of brain imaging used. Although CCMs have been reported in infants and children, the majority become evident between the second and fifth decades with findings such as seizures, focal neurologic deficits, nonspecific headaches, and cerebral hemorrhage. Up to 50% of individuals with FCCM remain symptom free throughout their lives. Cutaneous vascular lesions are found in 9% of those with familial cerebral cavernous malformations (FCCM; see Diagnosis/testing) and retinal vascular lesions in almost 5%.
A permanent mark created by the insertion of pigment below the skin.
A recombinant human immunoglobulin (Ig) G1 monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), with immune checkpoint inhibitory and antineoplastic activities. Ipilimumab binds to CTLA4 expressed on T-cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system.
An intermediate, locally aggressive blood vessel neoplasm characterized by the presence of spindle endothelial cells, and formation of capillary-sized and slit-like vascular channels. It is often associated with hemorrhage and hemosiderin deposition.
A benign mesenchymal neoplasm that usually arises in the superficial soft tissues of the vulva or inguinal and scrotal regions. It is characterized by the presence of a cellular fibroblastic proliferation in an edematous to fibrous stroma containing numerous vessels.
A benign but highly vascular nasopharyngeal neoplasm. The tumor originates from the sphenopalatine foramen and involves both the pterygopalatine fossa and the posterior nasal cavity.
A morphologic variant of angiofibroma characterized by the presence of multinucleated giant cells, collagenous or myxoid stroma, focal sclerotic areas, and angiectoid spaces.
A low grade malignant neoplasm arising from the long bones. The tibia is the most frequently affected bone site. Patients present with swelling which may or may not be associated with pain. Morphologically, it is characterized by a biphasic pattern consisting of an epithelial and an osteofibrous component. The vast majority of cases recur if they are not treated with radical surgery. In a minority of cases the tumor may metastasize to other anatomic sites including lymph nodes, lungs, liver, brain, and skeleton.
An extranodal marginal zone lymphoma that arises from the lung. It is characterized by the neoplastic proliferation of small B-lymphocytes, monocytoid cells and cells with plasma cell differentiation in the marginal zones of reactive lymphoid follicles. The neoplastic cells infiltrate the interfollicular areas and the bronchial epithelium forming lymphoepithelial lesions. The neoplasm is usually discovered as a mass in a chest x-ray in asymptomatic patients. When symptoms occur, they include cough, dyspnea, hemoptysis, and chest pain. If the lung lesions are resectable, surgery can result in prolonged remission.
A low-grade, extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue that arises from the skin. It usually presents with multifocal papular or nodular lesions in the arms or trunk. It rarely disseminates to internal organs or progresses to high grade lymphoma.
A usually indolent mature B-cell lymphoma, arising from the marginal zone of lymphoid tissues. It is characterized by the presence of small to medium sized atypical lymphocytes. It comprises three entities, according to the anatomic sites involved: extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, which affects extranodal sites (most often stomach, lung, skin, and ocular adnexa); nodal marginal zone B-cell lymphoma, which affects lymph nodes without evidence of extranodal disease; and splenic marginal zone B-cell lymphoma, which affects the spleen and splenic hilar lymph nodes, bone marrow, and often the peripheral blood.
An adenocarcinoma arising from the sweat glands. Most cases present as nodular lesions on the digits, usually in the hands. It is characterized by the presence of epithelial cells in the dermis forming nodules. Cystic structures containing papillary projections are also present. It may recur and metastasize, most commonly to the lungs.
A WHO grade II or III pineal parenchymal neoplasm of intermediate-grade malignancy, affecting all ages. It is composed of diffuse sheets or large lobules of uniform cells with mild to moderate nuclear atypia and low to moderate level mitotic activity. (Adapted from WHO)
A basal cell carcinoma of the skin characterized by the presence of small nodules that permeate the dermis. It presents as an elevated or flat infiltrating tumor, usually in the back.
A primary malignant neoplasm of the ureter which has spread either into adjacent tissues or to a distant site.
A primary malignant neoplasm of the urethra which has spread either into adjacent tissues or to a distant site.
A variant of mycosis fungoides, characterized by an exclusively intraepidermal atypical (cerebriform) lymphocytic infiltrate. Patients present with a localized psoriasiform or hyperkeratotic patch or plaque, usually in the extremities. Extracutaneous dissemination of the disease has never been reported.
A malignant neoplasm composed of large cells with large nuclei, prominent nucleoli, and abundant pale cytoplasm (Paget cells). Paget cell neoplasms include Paget disease of the nipple and extramammary Paget disease which may affect the vulva, penis, anus, skin and scrotum.
A neuroendocrine tumor arising from the delta cells of the pancreas. It is characterized by inappropriate secretion of somatostatin and associated with diabetes mellitus, hypochlorhydria, gallbladder disease, diarrhea, steatorrhea, anemia, and weight loss.
A raised vasculitic hemorrhage into the skin and/or mucous membranes.
A neuroendocrine tumor arising from the pancreas. It is characterized by inappropriate secretion of gastrin and associated with Zollinger Ellison syndrome. The latter is characterized by the presence of peptic ulcer, gastroesophageal reflux disease, abdominal pain, diarrhea, and malabsorption.
Depletion of stem cells in the bone marrow that results in the lack of production of hematopoietic cells.
A benign, localized, nodular and well-circumscribed neoplasm usually seen as a congenital neoplasm or in the first year of life. It is characterized by a biphasic growth pattern and is composed of small, undifferentiated mesenchymal cells associated with branching thin-walled vessels and more mature neoplastic spindle cells with abundant eosinophilic cytoplasm in a collagenous stroma.
A basal cell carcinoma that contains large amounts of melanin. The melanin is produced by symbiotic nontumoral proliferating melanocytes. - 2002.
A neoplasm composed of basal cells that metastasizes to other anatomic sites.
A neoplasm composed of at least two distinct cellular populations.
Carcinoma, predominantly squamous cell, arising from the epithelial cells of the hypopharynx.
A non-metastasizing neoplasm arising from the adrenal cortex. (NCI05)
A benign or malignant neoplasm that arises from and is composed of epithelial cells. This category include adenomas, papillomas, and carcinomas [NCIT:C3709].
A morphologic variant of Burkitt lymphoma characterized by marked nuclear pleomorphism, abundant apoptotic debris, and the presence of tangible body macrophages.
A benign, well circumscribed neoplasm arising from the sebaceous glands. It usually presents as a small yellowish tumor in the sun exposed skin of head and neck. It is characterized by the presence of sebaceous cells aggregates with a peripheral rim of basaloid cells.
A benign ovarian stromal tumor characterized by the presence of cellular areas which contain fibroblasts and round cells. The cellular areas are separated by sclerotic or edematous hypocellular tissue. Symptoms include abdominal discomfort and menstrual abnormalities.
A benign or malignant neoplasm arising during childhood.
A teratoma which may be cystic; it is composed entirely of well differentiated, adult-type tissues, without evidence of fetal-type tissues.
A rare, serous papillary adenocarcinoma that arises from the lining of the peritoneum. It affects females. The clinical behavior and pathologic characteristics are similar to the serous papillary adenocarcinoma that arises from the ovary.
Lobular neoplasia characterized by lobular epithelial proliferation that does not completely fill the lobular unit of the breast.
Any symptom or condition which is a result of a medical intervention but arises months or years after it.
An anal canal carcinoma which has spread to another anatomic site.
A granulosa-stromal cell tumor that arises from the ovary. It is characterized by the presence of granulosa cells that comprise at least ten percent of the cellular population. The granulosa cells are often found in a background that contains theca and fibrous cells. There are two major subtypes recognized, adult and juvenile granulosa cell tumor. Clinically, patients may present with an abdominal mass. Symptoms depend on the patient's age. The most important indicator of prognosis is tumor stage. Age over forty years at the time of the initial diagnosis, large tumor size, bilaterality, cellular atypia, and increased mitotic activity are factors indicating a potentially aggressive clinical course and relative poor prognosis.
The reemergence of plasma cell myeloma after a period of remission.
A variant of ependymoma, often found in the spinal cord, with tumor cells arranged in fascicles of variable width and cell density. Ependymal rosettes are generally absent, so this lesion must be distinguished from astrocytic neoplasms, but its EM characteristics are ependymal. (Adapted from WHO.)
A mature or immature teratoma affecting the central nervous system and occurring in adults.
A rare, WHO grade II cerebellar neoplasm which shows consistent neuronal, variable astrocytic and focal lipomatous differentiation. It occurs in adults, has a low proliferative potential and usually has a favorable prognosis. (Adapted from WHO)
A germ cell tumor that arises within the cranium and occurs during adulthood.
A WHO grade II, usually recurring meningioma characterized by the predominance of tissues that are histologically similar to chordoma.
A usually benign perineurioma not associated with a nerve, arising from the soft tissues.
A WHO grade I perineurioma that arises within the endoneurium. It is characterized by the formation of pseudo-onion bulbs by the proliferating perineural cells.
A schwannoma characterized by a plexiform or multinodular growth pattern. It usually arises from the skin or subcutaneous tissues in the extremities, trunk, and head and neck.
An uncommon benign neoplasm of the sweat glands characterized by the presence of clear cells.
A malignant neoplasm characterized by the presence of atypical mesenchymal-stromal cells. Representative examples include endometrial stromal sarcoma and prostate stromal sarcoma.
An adenocarcinoma that arises from the intrahepatic bile ducts, the hepatic ducts, or the extrahepatic bile ducts. Adenocarcinomas that arise from the intrahepatic bile ducts or the hepatic ducts are called cholangiocarcinomas.
Pathologic accumulation of air in the interstitium of the lungs, which is caused by the rupture of alveoli and terminal bronchioles, and is most often seen in premature infants that need mechanical ventilation for respiratory distress syndrome.
A hepatocellular carcinoma that occurs during childhood and has recurred after a period of remission.
The reemergence of a malignant salivary gland neoplasm after a period of remission.
A locally aggressive malignant neoplasm composed of mature adipocytes showing cell size variation and nuclear atypia. It is often associated with the presence of hyperchromatic multinucleated stromal cells, and varying numbers of lipoblasts. There are three histologic subtypes, sclerosing, inflammatory, and spindle cell liposarcoma. These tumors do not usually metastasize unless they undergo dedifferentiation.
A rare morphologic variant of well differentiated liposarcoma occurring most often in the retroperitoneum. It is characterized by the presence of a predominant inflammatory infiltrate composed of lymphoplasmacytic aggregates.
A phyllodes tumor with morphologic characteristics which are intermediate between a benign and a malignant phyllodes tumor. The stromal sarcomatous changes are of low grade and are often reminiscent of low grade fibrosarcomas.
The reemergence of optic nerve glioma in childhood after a period of remission.
Tumor is clinically localized to the periprostatic area, but extends through the prostatic capsule; the seminal vesicles may be involved. -- 2004
Tumor is clinically palpable but confined to the prostate. -- 2004
A clinically undetectable tumor confined to the prostate gland, normally an incidental finding during surgery. -- 2004
This entity represents a spectrum of lymphoproliferative disorders characterized by CD30 (Ki-1)-positive cutaneous T-cell infiltrates. The two ends of the spectrum include lymphomatoid papulosis (benign end) and primary cutaneous anaplastic large cell lymphoma (malignant end). Borderline lesions are also included in this spectrum. (WHO, 2001)
A human plasma-derived immunoglobulin G (IgG) formulation containing high levels of antibodies against varicella zoster virus (VZV), a double-stranded DNA virus that causes chickenpox and herpes zoster (shingles), with potential immunomodulating and antiviral activities. VZV IgG (VZIG) is isolated from donors expressing high amounts of VZV antibodies. Upon intramuscular (IM) administration, the anti-VZV antibodies provide passive immunization against VZV. This may prevent infection by VZV in immunocompromised patients.
Any substance that inhibits thymidylate synthase, an enzyme that catalyzes the conversion of uridine monophosphate to thymidine monophosphate, the rate-limiting step in de novo production of dTMP. Inhibition of thymidylate synthase causes inhibition of DNA synthesis and cell proloferation.
Any substance that inhibits nitric oxide synthase, an enzyme that catalyzes the production of nitric oxide from L-arginine. Nitric oxide is an important intercellular signaling molecule and inhibition of nitric oxide synthase effects many wide-ranging body processes and systems.
A germ cell tumor arising from brain during childhood.
A mature or immature teratoma affecting the central nervous system and occurring in children.
A choriocarcinoma that arises from the central nervous system and occurs during childhood.
An embryonal carcinoma that arises from the central nervous system and occurs during childhood.
A benign or malignant mesothelial neoplasm that arises from the peritoneum.
A yolk sac tumor that arises from the central nervous system and occurs during childhood.
A benign or malignant neoplasm of the brain, spinal cord, or meninges occurring in children. Representative examples include posterior fossa astrocytoma, optic pathway glioma, medulloblastoma, ependymoma, and craniopharyngioma.
A benign or malignant neoplasm of the brain, spinal cord, or meninges occurring in adults. Representative examples of primary neoplasms include astrocytoma, meningioma, pituitary adenoma, and neurilemoma. Representative examples of tumor metastases from other organs to the central nervous system include lung and breast carcinoma.
A non-neoplastic hamartomatous polyp that arises from the colon and rectum. It is characterized by the presence of tortuous and cystically dilated glands, edematous changes, and inflammation.
The reemergence of a nasopharyngeal malignant neoplasm after a period of remission.
A carcinoma of the oral cavity that arises from the floor of the mouth. Representative examples include squamous cell carcinoma, mucoepidermoid carcinoma, and adenoid cystic carcinoma.
A malignant epithelial neoplasm arising in the nasal cavity.
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis. (AJCC 6th and 7th eds.)
Ataxia associated with chaotic multidirectional conjugate eye movements secondary to metastatic tumors to cerebellum. The most common malignant tumor associated with this paraneoplastic syndrome is lung carcinoma. (NCI)
An intermediate grade malignant bone-forming mesenchymal neoplasm with chondroblastic differentiation. It arises from the surface of the bone and affects the diaphysis or diaphyseal- metaphyseal portion of the long bones. A painless mass or swelling is the most common clinical sign. It is associated with a better prognosis than conventional osteosarcoma.
A benign neoplasm characterized by the presence of cystic structures lined by mucinous columnar epithelial cells in a fibrotic stroma.
A biphasic polypoid neoplasm characterized by the presence of papillary projections that are lined by epithelial cells and fibrotic stroma.
A benign neoplasm characterized by the presence of cystic glandular and fibrous tissues and clear cells.
Malignant testicular germ cell tumor that is resistant to treatment.
A papillary transitional cell carcinoma that arises from the renal pelvis.
A neoplasm that arises from the mesothelial cells of the pleura. The primary cause is exposure to asbestos. The major histologic variants are the epithelioid malignant mesothelioma, desmoplastic malignant mesothelioma, and sarcomatoid malignant mesothelioma. Patients present with persistent cough and shortness of breath.
A benign neoplasm arising from vascular tissue usually of the skin. It is characterized by the presence of vascular channel formation and endothelial cells.
Stage I includes: T1, N0, M0. T1: Tumor confined to the nasopharynx. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.)
Stage III includes: (T1, N2, M0); (T2a, N2, M0); (T2b, N2, M0); (T3, N0, M0); (T3, N1, M0); (T3, N2, M0). T3: Tumor involves bony structures and/or paranasal sinuses. N2: Bilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa. M0: No distant metastasis. (AJCC 6th ed.)
An intraosseous odontogenic neoplasm with good prognosis, arising from the mandible and less frequently from the maxilla. It is characterized by the presence of stellate cells, myxoid stroma formation, and prominent collagen. Small tumors may be cured with enucleation. Complete excision may be required for larger tumors.
A usually benign neoplasm composed of large cells with abundant eosinophilic granular cytoplasm. Representative examples include oncocytic neoplasms of the thyroid gland, and kidney. (NCI05)
Stage II includes: (T2, N0, M0); IIA: (T2a, N0, M0); IIB (T2b, N0, M0); IIC (T2c, N0, M0). T2: Tumor involves one or both fallopian tubes with pelvic extension. T2a: Extension and/or metastasis to the uterus and/or ovaries. T2b: Extension to other pelvic structures. T2c: Pelvic extension with malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage I includes: (T1, N0, M0); IA (T1a, N0, M0); IB (T1b, N0, M0); IC (T1c, N0, M0). T1: Tumor limited to the fallopian tube(s). T1a: Tumor limited to one tube, without penetrating the serosal surface; no ascites. T1b: Tumor limited to both tubes, without penetrating the serosal surface; no ascites. T1c: Tumor limited to one or both tubes with extension onto or through the tubal serosa, or with malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage III includes: (T3, N0, M0); IIIA (T3a, N0, M0); IIIB (T3b, N0, M0); IIIC (T3c, N0, M0). T3: Tumor involves one or both fallopian tubes, with peritoneal implants outside the pelvis. T3a: Microscopic peritoneal metastasis outside the pelvis. T3b: Macroscopic peritoneal metastasis outside the pelvis 2cm or less in greatest dimension. T3c: Peritoneal metastasis more than 2cm in diameter. (AJCC 6th ed.) - 2003
Stage II carcinoma of the pharynx according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage III carcinoma of the pharynx according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
Stage IV carcinoma of the pharynx according to the American Joint Committee on Cancer, 6th, 7th, and 8th editions.
A benign squamous neoplasm characterized by a papillary growth pattern, diffusely involving a specific anatomic site.
Stage IV includes: Any T, Any N, M1. IVA: Any T, Any N, M1a. IVB: Any T, Any N, M1b. M1: Distant Metastasis. (AJCC 6th ed.) -2003
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB (T4b, Any N, M0); IVC (Any T, Any N, M1). T4a: Tumor invades the larynx, deep/extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible. T4b: Tumor invades lateral pterygoid muscle, pterygoid plates lateral nasopharynx, or skull base or encases carotid artery. M1: Distant Metastasis. (AJCC 6th ed.)
The reemergence of hypopharyngeal carcinoma after a period of remission.
The reemergence of ureter carcinoma after a period of remission
A carcinoma arising from the epithelium of the renal parenchyma or the renal pelvis. The majority are renal cell carcinomas. Kidney carcinomas usually affect middle aged and elderly adults. Hematuria, abdominal pain, and a palpable mass are common symptoms.
A primary or metastatic malignant neoplasm that affects the sternum.
An acute phenomenon characterized by hypotension and anasarca due to the loss of plasma volume into peripheral tissues, with evidence of decreased plasma volume (hemoconcentration) and protein loss from the intravascular space (hypoalbuminemia) during acute episodes. []
The hydrochloride salt of chloroquine, a synthetic quinoline with antimalarial and anti-inflammatory properties. Chloroquine is the most widely used drug against malaria, except for those cases caused by chloroquine resistant Plasmodium falciparum. Although the mechanism of action is not fully understood, chloroquine is shown to inhibit the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. Chloroquine may also interfere with the biosynthesis of nucleic acids.
Enlargement of the HEART due to chamber HYPERTROPHY, an increase in wall thickness without an increase in the number of cells (MYOCYTES, CARDIAC). It is the result of increase in myocyte size, mitochondrial and myofibrillar mass, as well as changes in extracellular matrix.
An ependymoma which shows conspicuous cellularity without a significant increase in mitotic rate. (Adapted from WHO)
A WHO grade I meningioma characterized by the presence of epithelial differentiation and numerous intracellular PAS positive bodies that are rich in glycogen.
A WHO grade I meningioma characterized by the presence of a prominent mesenchymal component. The mesenchymal component may be osseous, cartilaginous, myxoid, lipomatous, or a mixture of mesenchymal elements.
A WHO grade I meningioma characterized by the presence of intercellular microcystic spaces that contain mucinous fluid.
A sarcoma arising from the leptomeninges.
An epithelial hyperplasia on the surface of the tongue associated with Epstein-Barr virus and found almost exclusively in persons with HIV infection. The lesion consists of a white patch that is often corrugated or hairy.
Birth of the fetus through the vagina without the application of vacuum or forceps or any other instrument. (adapted from reVITALize)
Inflammation of a mucous membrane with increased flow of mucous in humans or animals. Catarrh is used mostly in a historical context.
A carcinoma which has spread from the original site of growth to another anatomic site.
A form of hyperaldosteronism caused by a defect within the adrenal gland.
Testicular failure due to a condition directly affecting the testes.
In the evaluation of male infertility, the Sertoli cell-only (SCO) syndrome is diagnosed on testicular biopsy when either no germ cells are visible in any seminiferous tubules (SCO type I) or germ cells are present in a minority of tubules (SCO type II). It is believed that the latter variant arises from a failure to complete differentiation and maturation of spermatocytes and spermatids, leading to degeneration of germ cells within most tubules (Sargent et al., 1999). There is evidence that Sertoli cell-only syndrome can be caused by interstitial deletions in the 'azoospermia factor' (AZF) region on the long arm of the Y chromosome (SPGFY1; 400042). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Myocarditis that is caused by an infection with a bacterial agent.
A significant descent of the kidney as the patient moves from the supine to the erect position.
A category of juvenile idiopathic arthritis defined by the presence of arthritis and high fevers, and accompanied by at least 2 of the following systemic features: lymphadenopathy, organomegaly, rash, or serositis. Macrophage activation syndrome is a well known complication.
The presence of arthrosis, i.e., of degenerative joint disease, affecting the cervical vertebral column.
An orally bioavailable 4-anilinoquinazoline. ZD-6474 selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGF2), thereby blocking VEGF-stimulated endothelial cell proliferation and migration and reducing tumor vessel permeability. This agent also blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that mediates tumor cell proliferation and migration and angiogenesis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=269177&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=269177&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2737"" NCI Thesaurus)
A decreased magnitude of the sensory perception of sound. [HPO:probinson]
Congenital abnormality where one, instead of the usual two, UMBILICAL ARTERY connects the fetus to the placenta.
Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy).
A benign neoplasm of the bladder that involves the transitional epithelium projecting above the surrounding epithelial surface and consisting of villous or arborescent outgrowths of fibrovascular stroma.
Ancylostomiasis that is caused by infection by Ancylostoma Duodenale.
Small hands and feet in proportion to the rest of the body. [HPO:probinson, PMID:22043168]
Recurrent attacks of severe anxiety, whose occurence is not restricted to any particular situation or set of circumstances and is therefore unpredictable. []
An abnormal localized widening (dilatation) of the descending thoracic aorta. []
A rare, benign and well circumscribed neoplasm that arises from the breast. It is characterized by the proliferation of epithelial cells with extensive apocrine metaplasia.
Congenital absence of the normal opening of a structure of the urinary tract.
A defect of the atrioventricular septum of the heart.
A congenital heart defect characteizred by a specific combination of heart defects with a common atrioventricular valve, primum atrial septal defect and inlet ventricular septal defect.
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Atrophy of the peroneous muscles, peroneus longus (also known as Fibularis longus), Peroneus brevis (also known as fibularis brevis, and Peroneus tertius (also known as fibularis tertius).
The presence of calcium deposition affecting one or more structures of the basal ganglia.
Developmental hypoplasia of the parathyroid gland.
Bleeding within the fundus of the eye. []
The presence of hemorrhage within the body.
The health and other ramifications of military and civilian exposure to WAR .
An abnormally increased tendency to fractures of bones caused by an abnormal reduction in bone strength that is generally associated with an increased risk of fracture.
Any disorder of the muscles and bones occurring as a consequence of injury to the musculoskeletal system.
A large maternal clot that separates the chorionic place from the villous chorion.
A type of anterior polar cataract which projects as a conical opacity into the anterior chamber.
A 'coral-like' pattern of opacity in the lens of the eye. That is, a cataract with an irregular, stellate form.
A necrotic process affecting the brain and/or spinal cord.
Abnormal enlargement of one or both hands, along with hyperhydrosis.
A type of cirrhosis characterized by the presence of regenerative nodules of a variety of sizes.
Pertaining to or characterized by cognition. That operation of the mind which we become aware of objects of thought or perception; it includes all aspects of perceiving, thinking, or remembering.
A rare larynx anomaly with a cyst involving the larynx or supraglottis locations, such as the epiglottis and vallecula. Timing and severity of presentation depend on the size of the cyst and its proximity to the glottis and range from severe prenatal airway obstruction leading to polyhydramnios and pulmonary hypoplasia to postnatal inspiratory stridor associated with muffled cry, hoarseness and cyanotic episodes, feeding difficulties and failure to thrive. It can be associated with laryngomalacia.
Multiple bent (flexed) finger joints that cannot be straightened actively or passively.
A mild form of hypospadias in which the urethra opens just under the corona glandis. [HPO:probinson]
A condition characterized by the herniation of the bladder into the vagina due to tearing of the tough fibrous wall between a woman's bladder and her vagina (the pubovesical fascia).
The presence of multiple diverticula of the intestine.
Congenital pernicious anemia (PA), or intrinsic factor deficiency, is a rare disorder characterized by the lack of gastric intrinsic factor in the presence of normal acid secretion and mucosal cytology and the absence of GIF antibodies that are found in the acquired form of pernicious anemia (170900). See also pernicious anemia due to defect in the receptor for vitamin B12/intrinsic factor (261100).
A deep folliculitis due to a cutaneous dermatophyte infection, usually on the legs. It is most commonly caused by trichophyton rubrum and is characterized by the formation of spongy granulomas which persist for three to four months and leaves deep scars.
An obstruction of a vessel caused by a detached fragment of an indwelling dialysis catheter.
Blockage of a dialysis catheter by a thrombus or other substance.
The presence of multiple diverticula of the intestine. [HPO:probinson]
A population of lymphocytes from the blood of a donor and administered to a patient who has already received a stem cell transplant from the same donor (Allogeneic Hematopoietic Stem Cell Transplantation). The donor lymphocytes may be able to boost the patient's immune system and kill remaining cancer cells.
Supernumerary digits located at the radial side of the hand. Polydactyly (supernumerary digits) involving the thumb occurs in many distinct forms of high variability and severity. Ranging from fleshy nubbins over varying degrees of partial duplication/splitting to completely duplicated or even triplicated thumbs or preaxial (on the radial side of the hand) supernumerary digits.
A disorder characterized by impaired ability to comprehend numerical representation and rules, recall numerical facts, and perform arithmetic and related operations due to innate neurological lesion in areas of the brain that are important in numerical processing.
A type of eczema that occurs in the lips and perioral area.
A type of encephalopathy (brain disease, damage, or malfunction accompanied by an altered mental state) that is characterized by evidence of necrosis of brain tissue.
A morphologic finding indicating the alteration of the mature endometrial glandular epithelium to another that differs from that of normal endometrioid glands.
A type of cyclophoria (latent strabismus in which the occluded eye wheel-rotates on dissociation.) in which the upper poles of the globes are rotated outward (laterally) to each other. []
The presence of calcium deposition in the falx cerebri.
A disorder characterized by a necrotic process occurring in the pharynx.
A disorder characterized by an abnormal communication between the ileum and another organ or anatomic site.
A disorder characterized by an abnormal communication between the larynx and another organ or anatomic site.
An abnormal communication between the lung and another organ or anatomic site.
Birth at greater than or equal to 42 weeks and 0 days.
Width of the palate more than 2 SD below the mean (objective) or apparently decreased palatal width (subjective).
Cleft lip and cleft palate affecting both sides of the face.
A gap (cleft) affecting one of the alveolar ridges, which are the protuberances in the mouth that contain the sockets (alveoli) of the teeth. An alveolar cleft can affect all structures of the alveolar ridge, including the gingiva, other mucosa, periosteum, alveolar bone, and teeth.
Increase in body weight of the mother during the course of her PREGNANCY.
Accumulation of calcium salts in the pineal gland.
Growth arrest lines are alternating transverse rings of sclerosis at the metaphysis of a long bone.
A collection of blood into the space between the pia membrane and arachnoid membrane.
A primary headache disorder that is similar to the CLUSTER HEADACHE with unilateral head pain, but differs by its multiple short severe attacks. It is usually seen in females, and may be responsive to non-steroidal-anti-inflammatory drugs (NSAIDS).
The criteria for the hemifacial type of congenital hypertrophy are (1) unilateral enlargement of the viscerocranium bounded superiorly by the frontal bone (not including the eye), inferiorly by the inferior border of the mandible, medially by the midline of the face, and laterally by the ear, the pinna being included within the hypertropic area, and (2) enlargement of all tissues--teeth, bone, and soft tissue--within this area (Rowe, 1962).
A general term referring to a defect in immunity resulting from impaired antibody production.
A fluid-filled VAGINA that is obstructed.
Hypothyroidism due to insufficient intake of iodine.
A disorder characterized by blockage of the normal flow of the intestinal contents in the ileum.
A type of cyclophoria (latent strabismus in which the occluded eye wheel-rotates on dissociation.) in which the upper poles of the globes are rotated inward (medially) to each other. [ORCID:0000-0003-0986-4123]
A local or systemic infection associated with the use of a dialysis catheter.
Inflammation of the meninges and brain caused by an infectious agent.
A condition in which there is inadequate blood flow through the peripheral blood vessels due to intrinsic disease of the vasculature.
A type of ectopic pregnancy in which the extrauterine EMBRYO IMPLANTATION occurs in the portion of the FALLOPIAN TUBE that traverses the muscular wall of the uterus.
A disorder characterized by blockage of the normal flow of the intestinal contents in the jejunum.
Surgery to remove a lens and replace it with an artificial lens.
A term that refers to a pathologic process in its original anatomic site of growth.
A benign or malignant teratoma that arises from the liver.
Abnormal anatomical location of the stomach. This feature may be due to intestinal malrotation.
Increased size and molar morphology of premolar tooth.
A benign proliferation of pigment cells of the oral mucosa producing brown or bluish dome-shaped or sessile mass, usually with a smooth surface.
Damage to the laryngeal nerve that results in paralysis of the layrnx.
Kidney damage resulting from exposure to drugs.
An abnormal communication between the pleural cavity and another anatomic site.
A rare, paralytic poliomyelitis associated with the orally administered live attenuated strain of the poliovirus, OPV.
Blood-tinged vaginal secretion in a neonate that results from the residual influence of maternal estrogen.
Missing radius bone associated with congenital failure of development. [HPO:probinson]
Persons adversely effected by DISASTERS, occurrences that result in property damage, deaths, and/or injuries to a community.
A disorder characterized by blockage of the normal flow of the intestinal contents in the rectum.
The presence of cells with and without three copies of chromosome 21 in either somatic or germinal tissue.
One or more bent (flexed) toe joints that cannot be straightened actively or passively.
A condition characterized by excessive fatigue and lack of energy, increasing irritability, and feelings of demoralization. Persons who experience this condition are not at an increased risk for cancer.
Rotated position of the glans, with or without the penile shaft, of 30 degrees or more.
Refers to an underlying pathologic process that has not been identified.
Congenital or acquired blockage of the vagina.
A vertical gaze palsy with inability to direct the gaze of the eyes downwards.
Complete absence of any auricular structures.
Ossification affecting the external ear cartilage.
Incisor that has marked lateral borders occurring lingually.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in a cerebral artery.
A specific learning disability involving mathematics and arithmetic.
Any condition characterized by an inability to regulate body temperature.
Ischemic tissue injury produced by insufficient perfusion of intestinal tissue by the MESENTERIC CIRCULATION (i.e., CELIAC ARTERY; SUPERIOR MESENTERIC ARTERY; INFERERIOR MESENTERIC ARTERY; and MESENTERIC VEINS). It can progress from ISCHEMIA; EDEMA; and GANGRENE of the bowel wall to PERITONITIS and cardiovascular collapse.
Historical term that references a form of pneumonia caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae, or Legionella species.
Neoplasms that are located in the pineal gland. These neoplasms arise either from pineal parenchymal cells (pineocytes), as do pineocytomas and the more aggressive pineoblastomas, or from other cell types, as do pineal astrocytic tumors (notably pilocytic astrocytomas) and germ cell tumors. Clinical symptoms include neuro-ophthalmologic dysfunction, changes in mental status, dysfunction of the brain stem, and hypothalamic-based endocrine abnormalities.
A carcinoma arising from the sweat glands. Representative examples include tubular carcinoma, spiradenocarcinoma, eccrine carcinoma, hidradenocarcinoma, and apocrine carcinoma.
A squamous cell carcinoma (SCC) arising from the anal canal or the anal margin (perianal skin). Human papillomavirus is detected in the majority of cases. Homosexual HIV-positive men have an increased risk of developing anal squamous cell carcinoma in comparison to the general male population. Symptoms include anal pruritus, discomfort when sitting, pain, change in bowel habit, and bleeding. The prognosis is generally better for anal margin SCC than for anal canal SCC.
A squamous cell carcinoma arising from the perianal skin.
Mental retardation, microcephaly, spastic diplegia, seizures, and mild aminoaciduria are the principal features. Seemanova syndrome 1 and Paine syndrome are considered as variants of the same entity termed Paine-Seemanova syndrome.
Dystonia-6 is an autosomal dominant movement disorder characterized by early involvement of craniofacial muscles with secondary generalization often involving the arms, and laryngeal dystonia that causes speech difficulties (review by Djarmati et al., 2009). Blanchard et al. (2011) provided a review of dystonia-6 and the THAP1 gene.
The more common form of transposition of the great arteries, dextro-looped TGA, consists of complete inversion of the great vessels, so that the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the left ventricle. (In the less common type of TGA, levo-looped TGA, the ventricles are inverted instead) (Goldmuntz et al., 2002). This creates completely separate pulmonary and systemic circulatory systems, an arrangement that is incompatible with life. Patients with TGA often have atrial and/or ventricular septal defects or other types of shunting that allow some mixing between the circulations in order to support life minimally, but surgical intervention is always required. For a discussion of genetic heterogeneity of dextro-looped transposition of the great arteries, see 608808.
Cone-rod dystrophy is a group of related eye disorders that causes vision loss, which becomes more severe over time. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with cone-rod dystrophy, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.The first signs and symptoms of cone-rod dystrophy, which often occur in childhood, are usually decreased sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). These features are typically followed by impaired color vision (dyschromatopsia), blind spots (scotomas) in the center of the visual field, and partial side (peripheral) vision loss. Over time, affected individuals develop night blindness and a worsening of their peripheral vision, which can limit independent mobility. Decreasing visual acuity makes reading increasingly difficult and most affected individuals are legally blind by mid-adulthood. As the condition progresses, individuals may develop involuntary eye movements (nystagmus).There are more than 30 types of cone-rod dystrophy, which are distinguished by their genetic cause and their pattern of inheritance: autosomal recessive, autosomal dominant, and X-linked. Additionally, cone-rod dystrophy can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body.
A drug derived from a betulinic acid-like compound, first isolated from the Chinese herb Syzygium claviflorum, with activity against human immunodeficiency virus (HIV). Bevirimat acts by binding to the Gag capsid precursor protein and blocking its conversion to mature capsid protein by protease cleavage. It potently inhibits replication in both wild-type and drug-resistant (reverse transciptase or protease) HIV-1 isolates.
A symmetrical dimeric bis-naphthalimide compound and a topoisomerase II inhibitor with antineoplastic activity. Elinafide contains two neutral chromophores joined by a cationic linker and is capable of bis-intercalation at the TpG and CpA steps of the DNA hexanucleotide. Intercalation inhibits topoisomerase II activity and causing DNA stand breakage, thereby leads to inhibition of DNA, RNA, and protein synthesis.
A monoclonal antibody that selectively binds with KDR and blocks the vascular endothelial growth factor-induced endothelial cell proliferation and prevents angiogenesis. (NCI)
A recombinant chimeric protein with potent antitumor activity. Cintredekin besudotox is composed of interleukin-13 (IL13), a pleiotropic immunoregulatory cytokine, linked to a mutated form of pseudomonas exotoxin A; this agent targets and kills tumor cells that express the IL13 receptor (IL13R).The IL13 moiety attaches to the IL13R on the tumor cell membrane, facilitating the entry of the exotoxin. The exotoxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis.
A humanized monoclonal antibody against CD4, with anti-human immunodeficiency virus (HIV) activity. Ibalizumab binds to CD4, the primary receptor for HIV, thereby inhibiting HIV entry into CD4-positive T-cells. This leads to a reduction in viral load.
A synthetic derivative of inosinic acid with antiretroviral and immunomodulatory properties. Atvogen acts through a number of pathways to stimulate intracellular antiviral activity of the immune system: it stimulates interferon production; activates the oligoadenylate synthase-RNase L pathway; stimulates natural killer cell activity; and acts as a non-mitogenic stimulator of the immune system. This agent also inhibits replication of human immunodeficiency virus (HIV) in vitro. (NCI04)
A diarylpyrimidine non-nucleoside reverse transcriptase inhibitor. Dapivirine has activity against wild-type virus strains and strains harboring different NNRTI resistance-inducing mutations and may have direct virucidal activity.
A member of the tyrphostin family of tyrosine kinase inhibitors, that actively blocks lipopolysaccharide-induced production of tumor necrosis factor-a and nitric oxide in macrophages. (NCI)
A synthetic, antiestrogenic steroidal compound with potential antitumor activity. TAS-108 binds to and inhibits estrogenic receptor alpha (ERa), mainly expressed in the mammary gland and uterus and upregulated in estrogen-dependent tumors. Blockage of ERa by TAS-108 prevents the binding and effects of estrogen and may lead to an inhibition of estrogen-dependent cancer cell proliferation. TAS-108 also is a partial agonist of the estrogenic receptor beta (ERb), expressed in many tissues including the central nervous system, urogenital tract, bone and cardiovascular system, thereby exerting a positive effect on these tissues. In addition, TAS-108 activates the co-repressor Silencing Mediator for Retinoid and Thyroid hormone receptor (SMRT), a protein that inhibits the activities of the estrogen receptors, which may contribute to the antitumor activity of TAS-108.
An HIV PROTEASE INHIBITOR that is used in the treatment of AIDS and HIV INFECTIONS. Due to the emergence of ANTIVIRAL DRUG RESISTANCE when used alone, it is administered in combination with other ANTI-HIV AGENTS.
An orally-active synthetic hydroxamic acid derivative with potential antineoplastic activity. MMI270 inhibits a broad spectrum of matrix metalloproteinases (MMPs) (specifically MMP-1, 2, 3, 9, and 13), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. This agent may also downregulate lymphangiogenesis, resulting in decreased lymphatic system-related metastasis. (NCI04)
A melphalan prodrug in which the alkylating agent melphalan is bound to flufenamide, with potential antineoplastic and anti-angiogenic activities. Upon administration, the dipeptide bond in the melphalan-flufenamide compound is hydrolyzed by peptidases, which are overexpressed by certain cancer cells. This results in the specific release and accumulation of the active metabolite melphalan in cancer cells. Melphalan alkylates DNA at the N7 position of guanine residues and induces DNA intra- and inter-strand cross-linkages. This results in the inhibition of DNA and RNA synthesis and the induction of apoptosis, thereby inhibiting tumor cell proliferation. The administration of the melphalan-flufenamide prodrug allows for enhanced efficacy and reduced toxicity compared to melphalan alone.
Polyketides of up to a few dozen carbons in length, formed by chain extension of multiple PROPIONATES and oxygenated to form tetrahydrofuran and lactone rings along the length of the chain. They are found in ANNONACEAE and other PLANTS. Related compounds cyclize to MACROLIDES.
A nonbenzodiazepine, cyclopyrrolone and active stereoisomer of zopiclone with hypnotic and sedative activity and without significant anxiolytic activity. Although the exact mechanism of action remains to be fully elucidated, eszopiclone is able to bind to and activate the omega-1 subtype of the alpha subunit of the gamma-aminobutyric acid-benzodiazepine GABA receptor complex (GABA-A), a chloride ionophore complex in the central nervous system (CNS). This leads to the opening of chloride channels, causing hyperpolarization, inhibition of neuronal firing, and enhancement of the inhibitory effect of GABA. This eventually leads to a hypnotic effect and allows for an induction of sleep.
The liposomal formulation of a c-raf-1 antisense oligonucleotide, with potential antineoplastic activity. Liposomal c-raf antisense oligonucleotide targets the translation initiation site of human c-raf-1 mRNA, thereby blocking the expression and production of Raf-1 protein and thus inhibit tumor cell growth and development. Raf-1 plays a key role in the RAF/MEK/ERK signaling pathway, which regulates mammalian cell proliferation and growth. The liposomal formulation increases the solubility of the c-raf antisense oligonucleotide, thus improving its pharmacodynamic profile.
A glycogen phosphorylase inhibitor with antihyperglycemic and cardioprotective activities. Ingliforib inhibits glycogen phosphorylase, the rate-limiting enzyme in glycogenolysis, thereby preventing the release of glucose-1 phosphate from a glycogen molecule in liver. This agent also inhibits glycogen phosphorylase in cardiac muscle and may protect the heart from myocardial ischemic injury by preserving glycogen content and improving glycolytic-oxidative coupling.
An orally bioavailable, synthetic analog of the fatty acid oleic acid, with potential antitumor activity. Upon administration, 2-hydroxyoleic acid (2OHOA) activates sphingomyelin synthase (SMS), thereby increasing the concentration of sphingomyelin (SM) and diacylglycerol (DAG) in the tumor cell membrane and decreasing membrane levels of phosphatidylethanolamine (PE) and phosphatidylcholine (PC). This restores the normal, healthy levels and ratios of membrane lipids. By restoring normal membrane lipid structure and composition, this agent inhibits membrane-protein associated signaling and the aberrant activity of signaling pathways in certain tumor cells, including the Ras/MAPK and PI3K/AKt pathways. This inhibits tumor cell proliferation, induces tumor cell differentiation, and eventually can cause cell death.
Carcinoma that is spread throughout the body.
A radioactive form of iodine, often used for imaging tests or to treat an overactive thyroid, thyroid cancer, and certain other cancers. For imaging tests, the patient takes a small dose of radioactive iodine that collects in thyroid cells and certain kinds of tumors and can be detected by a scanner. To treat thyroid cancer, the patient takes a large dose of radioactive iodine, which kills thyroid cells. Radioactive iodine is also used in internal radiation therapy for prostate cancer, intraocular (eye) melanoma, and carcinoid tumors. Radioactive iodine is given by mouth as a liquid or in capsules, by infusion, or sealed in seeds, which are placed in or near the tumor to kill cancer cells.
Loss of a DNA sequence that contains one or more genes. This typically occurs via rearrangement, whereby DNA sequences that are normally separated become joined together. A gene deletion abnormality can be either heritable or somatic.
An acute infection of the upper or lower respiratory tract.
Irreversible damage to heart tissue (myocardium) due to lack of oxygen after a heart attack (myocardial infarction).
Intermittent, incomplete or complete paralysis with or without tremors to any of the organs or body parts innervated by the phrenic nerve.
An exostosis is a benign growth the projects outward from the bone surface. It is capped by cartilage, and arises from a bone that develops from cartilage.
The presence of a hernia in the abdominal wall.
A sterile solution containing culture filtrate of various Trichophyton species. It is used to test for delayed hypersensitivity to the fungus.
Infection of the lung often accompanied by inflammation that is acquired through an interaction within a healthcare institution often through a therapeutic experience (e.g., use of catheters or ventilators).
A form of myopia related to an axial length above the norm and too long for the refractive power of the whole optical system of the eye. [ORCID:0000-0003-0986-4123, PMID:24113300]
The reason the treatment was administered.
The retinal vessels stop and then a linear flat white line is present that usually runs the circumference of the vascular retina. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham, PMID:16009843]
The accumulating neovascularization thickens and manifests as a linear bump. The neovascularization remains along the surface of the retina and does not extend off the retina into the cortical vitreous. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
The neovascularization accumulates at the edge of the vascularized retina and extends into the vitreous (also called extra retinal fibrosis proliferation). In cases of Zone 2 and Zone 3, this may be sausage shaped. In more posterior Zone 1 disease, the stage 3 can appear as a direct extension of the normal retinal vessels but extending tangentially over the avascular retina. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
Scar tissue that forms a continuous sheet coming up from the edge of the vascularized retina. This scar tissue can grow toward the vitreous base/posterior lens capsule resulting in traction, distortion, and even detachment. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
Funnel detachment from the retina with generally traction in all four quadrants. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
Impaired ability to exercise reliance on beliefs and/or participate in rituals of a particular faith tradition.
Susceptible to an impaired ability to exercise reliance on religious beliefs and/or participate in rituals of a particular faith tradition, which may compromise health.
Any substance that inhibits the proteasome complex, an enzyme complex responsible for degradation of ubiquitinated proteins. Inhibition of proteasome activity and ubiquitin-proteasome mediated proteolysis results in an accumulation of poly-ubiquitinated proteins, which may result in the disruption of cellular processes, cell cycle arrest, the induction of apoptosis, and the inhibition of tumor growth and angiogenesis.
Small organic molecules that act as allosteric activators of the calcium sensing receptor (CaSR) in the PARATHYROID GLANDS and other tissues. They lower the threshold for CaSR activation by extracellular calcium ions and diminish PARATHYROID HORMONE (PTH) release from parathyroid cells.
Any tyrosine kinase inhibitor that targets the activity of the epidermal growth factor receptor (EGFR) tyrosine kinase. Inhibition of epidermal growth factor receptor tyrosine kinase may inhibit the growth of epidermal-lineage tumor cells, especially those that overexpress epidermal growth factor receptor.
The process by which an infection is transmitted to a person.
A chronic inflammatory process affecting the esophageal wall.
A congenital anatomic defect characterised by the absence of a normally present opening in an organ or tissue.
Mechanical limitation of the range of movement of the medial rectus muscle. [ORCID:0000-0003-0986-4123]
Mechanical limitation of the range of movement of the inferior rectus muscle. [ORCID:0000-0003-0986-4123]
State of a particular method of treatment, regimen, procedure, medication, etc. of being unsuitable and inadvisable, often because of a likely adverse reaction.
To stop or end, permanently or temporarily.
A term used to describe the state or condition of the completeness of the physical examination data.
Applied to pain that is described as sharp, i.e., sudden and severe.
A recombinant form of human bone morphogenetic protein 2 (rhBMP-2), with potential bone remodeling and osteoinductive activities. Following administration, rhBMP-2 induces BMP-2 signaling cascades, which leads to osteoblast differentiation, enhancement of bone repair and formation, and improvement of re-vascularization. This promotes bone healing. BMP-2, a protein belonging to the transforming growth factor beta (TGFb) superfamily of proteins, plays a key role in bone and cartilage formation.
Hormones made from cholesterol and protein produced by the adrenal glands and regulate electrolyte balance, blood pressure, inflammation, blood sugar balance, and immune system control.
A combination preparation of glucosamine, a hexosamine sugar polymer, and methyl sulfonyl methane (MSM), a derivative of dimethyl sulphoxide, with anti-arthritic and anti-inflammatory activities. The mechanism of action has not yet been fully elucidated but addition of glucosamine to chondrocytes results in inhibition of proteoglycan catabolism. Glucosamine inhibits interleukin-1-induced production of inflammatory mediators (nitric oxide, prostaglandin E2), and inhibit aggrecanase activity, which results in preservation of proteoglycan and chondrocytes. Other studies have also shown glucosamine to reduce the generation of reactive oxygen species by macrophages, and inhibit lysosomal enzymes. MSM has been suggested to exert its analgesic effect by inhibiting pain impulses along type C nerve fibers, reducing inflammation and muscle spasms, as well as promoting blood flow, thereby promoting the healing of cartilage lesions.
The hydrochloride salt form of Methaqualone. As a sedative, hypnotic agent, methaqualone was used for insomnia. Due to its high risk for abuse, methaqualone was taken off the U.S. market in 1983. (NCI)
A combination preparation containing phenylephrine, phenylpropanolamine and guaifenesin with decongestant and expectorant activities. Phenylephrine and phenylpropanolamine, direct-acting sympathicomimetic amines, activate alpha-adrenergic receptors in the nasal mucosa thereby causing vasoconstriction, reduces swelling of nasal mucous membranes and decreasing nasal and sinus congestion. Phenylpropanolamine also releases norepinephrine from its storage sites resulting in the effects already described. Guaifenesin increases respiratory tract mucus secretions and reduces the viscosity of mucus secretion by reducing adhesiveness and surface tension as well as increasing hydration of mucus, thereby increasing the efficiency of removing accumulated secretions from the upper and lower airways and making cough more productive.
A commercial combination preparation by Novartis containing acetaminophen, aspirin, and caffeine with analgesic activity. Acetaminophen exerts antipyretic and analgesic activities by inhibiting prostaglandin synthesis while aspirin, a salicylate, inhibits cyclooxygenases (COX) with anti-inflammatory, antipyretic and analgesic properties. Caffeine is a central nervous system stimulant and causes constriction of dilated cerebral blood vessels. Excedrin is used for the relief and treatment of migraine and tension headaches.
Difficulty in looking at another person in the eye.
A formulated therapeutic oral agent consisting of a combination of the 5-fluorouracil (5-FU) congener prodrug tegafur (tetrahydrofuranyl-5-fluorouracil) and uracil (1:4). The high concentration of uracil reversibly inhibits the uracil-reducing enzyme dihydropyrimidine dehydrogenase (DPD), thereby inhibiting first-pass DPD-mediated hepatic metabolism of the uracil analogue 5-FU and permitting administration of 5-FU as the orally bioavailable prodrug tegafur. Tegafur is bioactivated to 5-FU by liver microsomal cytochrome P450 enzymes. 5-FU is subsequently converted into its active metabolites 5-fluoro-deoxyuridine-monophosphate (FdUMP) and 5-fluorouridine-triphosphate (FUTP) intracellularly; these metabolites inhibit the enzyme thymidylate synthase and intercalate into RNA, resulting in decreased thymidine synthesis, reduced DNA synthesis, disrupted RNA function, and tumor cell cytotoxicity.
An L-tyrosine derived and peroxisome proliferator-activated receptor (PPAR) agonist with hypoglycemic and lipid lowering activity. Farglitazar shows greater selectivity over PPARgamma than PPARalpha. This agent is developed for the treatment of hepatic fibrosis.
Vaccines or candidate vaccines used to prevent EBOLA HEMORRHAGIC FEVER.
LMNA-related dilated cardiomyopathy (DCM) is caused by pathogenic variants in LMNA and is characterized by left ventricular enlargement and/or reduced systolic function preceded or accompanied by significant conduction system disease and/or arrhythmias. LMNA-related DCM usually presents in early to mid-adulthood with symptomatic conduction system disease or arrhythmias, or with symptomatic DCM including heart failure or embolus from a left ventricular mural thrombus. Sudden cardiac death can occur, and in some instances is the presenting manifestation; sudden cardiac death may occur with minimal or no systolic dysfunction.
Any of the enzymatically catalyzed modifications of the individual AMINO ACIDS of PROTEINS, and enzymatic cleavage or crosslinking of peptide chains that occur pre-translationally (on the amino acid component of AMINO ACYL TRNA), co-translationally (during the process of GENETIC TRANSLATION), or after translation is completed (POST-TRANSLATIONAL PROTEIN PROCESSING).
A subvariety of CADASIL characterized by the high frequency of MIGRAINE. The acronym stands for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts, Leukoencephalopathy, and Migraine.
Reduced motility of the gallbladder with reduced emptying fraction.
Tradename for histamine dihydrochloride.
Agents that antagonize ANGIOTENSIN II TYPE 1 RECEPTOR. Included are ANGIOTENSIN II analogs such as SARALASIN and biphenylimidazoles such as LOSARTAN. Some are used as ANTIHYPERTENSIVE AGENTS.
Breast diseases which are hormone-dependent or responsive to endocrine signals.
Gynecomastia that occurs during puberty and is not due to exogenous substances or disease processes.
Transient bilateral swelling of breast tissue in a neonate that results from the waning influence of maternal estrogen.
Myopia that increases at an abnormally rapid rate or increases after maturity (Hofstetter et al, Dictionary of Visual Science and Related Clinical Terms, 5th ed).
A multifactorial disease of CATTLE resulting from complex interactions between environmental factors, host factors, and pathogens. The environmental factors act as stressors adversely affecting the IMMUNE SYSTEM and other host defenses and enhancing transmission of infecting agents.
Autosomal dominant pseudohypoaldosteronism type I is characterized by salt wasting resulting from renal unresponsiveness to mineralocorticoids. Patients may present with neonatal renal salt wasting with hyperkalaemic acidosis despite high aldosterone levels. These patients improve with age and usually become asymptomatic without treatment. Some adult patients with the disorder may have elevated aldosterone levels, but no history of clinical disease. This observation suggests that only those infants whose salt homeostasis is stressed by intercurrent illness and volume depletion develop clinically recognized PHA I (summary by Geller et al., 1998). Autosomal recessive pseudohypoaldosteronism type I (PHA1B; 264350), caused by mutation in any one of 3 genes encoding the epithelial sodium channel (ENaC), is a similar but more severe systemic disorder with persistence into adulthood.
Autosomal recessive pseudohypoaldosteronism type I is characterized by renal salt wasting and high concentrations of sodium in sweat, stool, and saliva. The disorder involves multiple organ systems and is especially threatening in the neonatal period. Laboratory evaluation shows hyponatremia, hyperkalemia, and increased plasma renin activity with high serum aldosterone concentrations. Respiratory tract infections are common in affected children and may be mistaken for cystic fibrosis (CF; 219700). Aggressive salt replacement and control of hyperkalemia results in survival, and the disorder appears to become less severe with age (review by Scheinman et al., 1999). A milder, autosomal dominant form of type I pseudohypoaldosteronism (PHA1A; 177735) is caused by mutations in the mineralocorticoid receptor gene (MCR, NR3C2; 600983). Gitelman syndrome (263800), another example of primary renal tubular salt wasting, is due to mutation in the thiazide-sensitive sodium-chloride cotransporter (SLC12A3; 600968). Hanukoglu and Hanukoglu (2016) provided a detailed review of the ENaC gene family, including structure, function, tissue distribution, and associated inherited diseases.
A hereditary renal tubular defect characterized by hypertension and hyperkalemic metabolic acidosis in the presence of suppressed plasma renin levels and relatively low aldosterone levels.
Compounds based on ERYTHROMYCIN with the 3-cladinose replaced by a ketone. They bind the 23S part of 70S bacterial RIBOSOMES.
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
A reaction that introduces an aminoacyl group to a molecule. TRANSFER RNA AMINOACYLATION is the first step in GENETIC TRANSLATION.
A phospholipid with the polar ethanolamine found in phosphoester linkage to diacylglycerol.
The orally available hydrochloride salt of the opioid agonist noscapine, a phthalideisoquinoline alkaloid derived from the opium poppy Papaver somniferum, with mild analgesic, antitussive, and potential antineoplastic activities. Noscapine binds to tubulin and alters its conformation, resulting in a disruption of the dynamics of microtubule assembly (by increasing the time that microtubules spend idle in a paused state) and subsequently, the inhibition of mitosis and tumor cell death. Unlike other tubulin inhibitors such as the taxanes and vinca alkaloids, noscapine does not affect microtubule polymerization.
A human plasma-derived fibrin sealant that rapidly forms a clot.
A small aminothiazole molecule and cyclin dependent kinase (CDK) inhibitor with potential antineoplastic activity. SNS-032 binds to and prevents the phosphorylation of cyclin-dependent kinases, especially CDK2, 7, and 9 that regulate cell cycle progression. Inhibition of CDKs leads to cell cycle arrest and induces apoptosis. As a result, this agent causes cytotoxicity and prevents further tumor cell growth.
Single-chain polypeptides of about 65 amino acids (7 kDa) from LEECHES that have a neutral hydrophobic N terminus, an acidic hydrophilic C terminus, and a compact, hydrophobic core region. Recombinant hirudins lack tyr-63 sulfation and are referred to as 'desulfato-hirudins'. They form a stable non-covalent complex with ALPHA-THROMBIN, thereby abolishing its ability to cleave FIBRINOGEN.
A small molecule and a naphthyridine analogue with antineoplastic activity. Vosaroxin intercalates into DNA in a site-specific manner and blocks the re-ligation process carried out by topoisomerase II during DNA replication. As a result, inhibition of DNA replication, RNA and protein synthesis occurs, followed by cell cycle arrest at G2 phase and induced p53-independent apoptosis. This agent shows a favorable toxicity profile in several aspects: it does not generate reactive oxygen species, as do anthracyclines, hence reducing the risk of cardiotoxicity; it is not a P-glycoprotein (P-gp) substrate, and thereby evades the common mechanism for multidrug resistance; and it has limited distribution to normal tissues and a more chemically stable molecular structure.
A selective small-molecule activator of protein kinase C (PKC) isolated from the plant Euphorbia peplus with potential antineoplastic activity. Ingenol 3-angelate (I3A) activates various protein kinase C (PKC) isoforms, thereby inducing apoptosis in some tumor cells, including myeloid leukemia cells, melanoma cells, and basal cell carcinoma cells. The PKC family consists of signaling isoenzymes that regulate many cell processes including proliferation, differentiation, and apoptosis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=432941&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=432941&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48398"" NCI Thesaurus)
A piperazine-based CCR5 receptor antagonist with activity against human immunodeficiency virus. Vicriviroc is designed to bind to CCR5 and inhibit the entry of HIV into CD4 cells.
An orally available, acyclic retinoid with potential antineoplastic and chemopreventive activities. Peretinoin binds to and activates nuclear retinoic acid receptors (RAR), which in turn recruit coactivator proteins and promote, with other transcriptional complexes, the transcription of target genes. As a result, this agent may modulate the expression of genes involved in the regulation of cell proliferation, cell differentiation, and apoptosis of both normal and tumor cells.
A pentahydrochloride salt of omiganan, a synthetic cationic antimicrobial peptide with wide-spectrum activity against both gram-positive and gram-negative bacteria and fungi. Omiganan pentahydrochloride, an analog of indolicidin, acts by disrupting bacterial cytoplasmic membranes and has been tested in a topical gel for the prevention of catheter-related bloodstream infections.
The sodium salt of the trans-isomer of the carotenoid crocetin with potential antihypoxic and radiosensitizing activities. Trans sodium crocetinate (TSC) increases the diffusion rate of oxygen in aqueous solutions such as from plasma to body tissue. The agent has been shown to increase available oxygen during hypoxic and ischemic conditions that may occur in hemorrhage, vascular and neurological disorders, and in the tumor microenvionment.
A synthetic thymidine nucleoside analogue with antiviral activity highly specific for the treatment of hepatitis B virus (HBV). Intracellularly, telbivudine is phosphorylated to its active metabolite, telbivudine triphosphate. The dideoxy telbivudine triphosphate competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). This results in the blockade of HBV DNA replication and viral propagation.
A nucleoside inhibitor with activity against hepatitis B virus. Torcitabine is modified in vivo to its triphosphate form and acts as a competitive inhibitor of viral DNA polymerase.
An orally available, 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile, irreversible inhibitor of the HER-2 receptor tyrosine kinase with potential antineoplastic activity. HKI-272 binds to the HER-2 receptor irreversibly, thereby reducing autophosphorylation in cells, apparently by targeting a cysteine residue in the ATP-binding pocket of the receptor. Treatment of cells with this agent results in inhibition of downstream signal transduction events and cell cycle regulatory pathways; arrest at the G1-S (Gap 1/DNA synthesis)-phase transition of the cell division cycle; and ultimately decreased cellular proliferation. HKI-272 also inhibits the epidermal growth factor receptor (EGFR) kinase and the proliferation of EGFR-dependent cells. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=453548&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=453548&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C49094"" NCI Thesaurus)
A fumagillin analogue and inhibitor of methionine aminopeptidase 2 (METAP2), with potential antiangiogenic and anti-obesity activity. As an irreversible inhibitor, beloranib blocks METAP2's functions, which include both protecting eukaryotic initiation factor 2 from inhibitory phosphorylation during translation, and by removing the amino-terminal methionine residue from nascent protein permitting the conversion of an inactive or non-functional protein to an active one. As a result, this agent prevents endothelial cell growth and inhibits tumor angiogenesis. In addition, METAP2 inhibition also down-regulates ERK1/2 signaling pathway, which is usually overactive in the fat tissues of obese people. Therefore, at a much lower dose, beloranib can induce liver fat utilization and reduce cholesterol and fatty acid synthesis. METAP2, a member of the dimetallohydrolase family, plays an important role during angiogenesis and is over-expressed in various cancers.
A long-acting, synthetic peptide with gonadotrophin-releasing hormone (GnRH) antagonistic properties. Degarelix targets and blocks GnRH receptors located on the surfaces of gonadotroph cells in the anterior pituitary, thereby reducing secretion of luteinizing hormone (LH) by pituitary gonadotroph cells and so decreasing testosterone production by interstitial (Leydig) cells in the testes.
A pyrimidine and thiazole derived ANTINEOPLASTIC AGENT and PROTEIN KINASE INHIBITOR of BCR-ABL KINASE. It is used in the treatment of patients with CHRONIC MYELOID LEUKEMIA who are resistant or intolerant to IMATINIB.
An orally bioavailable, semi-synthetic lipophilic analogue of camptothecin, a quinoline alkaloid extracted from the Asian tree Camptotheca acuminate, with potential antineoplastic and antiangiogenic activities. Gimatecan binds to and inhibits the activity of topoisomerase I, stabilizing the cleavable complex of topoisomerase I-DNA, which inhibits the religation of single-stranded DNA breaks generated by topoisomerase I; lethal double-stranded DNA breaks occur when the topoisomerase I-DNA complex is encountered by the DNA replication machinery, DNA replication is disrupted, and the tumor cell undergoes apoptosis. Although the mechanism of its antiangiogenic activity has yet to be full elucidated, this agent may inhibit endothelial cell migration, tumor neovascularization, and the expression of proangiogenic basic fibroblast growth factor (bFGF).
Langerhans cell histiocytosis affecting the lungs. It is characterized by an interstitial proliferation of Langerhans cells in the lung parenchyma. Most patients are current or former smokers. Steroids are the mainstay therapy for this condition.
Acute fatty liver of pregnancy is a rare but severe complication occurring in the third trimester of pregnancy or in early postpartum period bearing a risk for perinatal and maternal mortality with manifestations of jaundice, rise of hepatic injuries and evolving to acute liver failure and encephalopathy.
Deficiency of parathyroid hormone with congenital onset.
Irreversible retardation of growth and psychomotor development due to child abuse.
An anti-cholesteremic agent that inhibits delta 7-reductase, delta 14 reductase, and sterol biosynthesis.
A dihydropyridine derivative, which, in contrast to NIFEDIPINE, functions as a calcium channel agonist. The compound facilitates Ca2+ influx through partially activated voltage-dependent Ca2+ channels, thereby causing vasoconstrictor and positive inotropic effects. It is used primarily as a research tool.
Lack of anterior tooth contact in any occluding position of the anterior teeth.
Lack of posterior tooth contact in any occluding position of the anterior teeth.
An abnormal dilation of the rectum. There is a large filled rectum as a result of underlying innervation or mulscular abnormalities, which remains after disimpaction of the rectum.
A weakened live virus vaccine containing three seasonal influenza reassortants with prophylactic activity against influenza subtypes A and B. The trivalent live-attenuated influenza vaccine (LAIV) contains 2 strains of the influenza subtype A, one for H1N1 and one for H3N2, and one strain of subtype B. Upon intranasal administration by sprayer of the trivalent LAIV, the live viruses replicate in the upper respiratory tract and induce an immune response leading to active immunization against influenza subtypes A and B.
A long-acting, fatty acylated glucagon-like peptide-1 (GLP-1) analog administered subcutaneously, with antihyperglycemic activity. Liraglutide's prolonged action and half-life of 11-15 hours are attributed to the attachment of the fatty acid palmitic acid to GLP-1 that reversibly binds to albumin. Albumin binding protects liraglutide from immediate degradation and elimination and causes GLP-1 to be released from abumin in a slow and consistent manner. This agent may cause thyroid C-cell tumors and increases the risk of acute pancreatitis.
A diarylpyrimidine non-nucleoside reverse transcriptase inhibitor. Etravirine is designed to be active against HIV isolates with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs. It can bind the enzyme reverse transcriptase (RT) in multiple conformations, both for native and mutant RT, thereby blocking the enzymatic activity of RT.
A class of polyphenolic compounds ranging in molecular weights from 500 to over 20,000 and are generally divided into 1)hydrolyzable tannins and 2)proanthocyanidins.
Having to do with, or derived from, plants.
The exposure to incident light from the sun.
A benign, circumscribed proliferation of melanocytes in the skin. Variants include the Spitz nevus, halo nevus, blue nevus, and balloon cell nevus.
A persecutory delusion of supposed hostility of others.
Pain, cramping, and fatigue of the lower extremities upon ambulation due to ischemia.
Delivery of newborn by means of a ventouse, a vacuum device used to assist the delivery of a baby when the second stage of labour has not progressed adequately. [DDD:hfirth]
A benign, intermediate, or malignant vascular neoplasm that arises from the skin.
Lawfully induced expulsion of all products of conception.
Subjective evidence of disease perceived by the patient.
Used with microorganisms, plants, and the postnatal period of animals for growth and development. It includes also the postnatal growth or development of organs or anatomical parts.
Having to do with the physical, psychological, cognitive, and social consequences of disease, including stigmatization of persons affected.
A malignant neoplasm arising from the blood vessels.
A coagulation disorder characterized by a tendency for excessive bleeding.
A rare, locally invasive neoplasm arising from tooth-forming tissues. It usually grows intraosseously in the mandible. The maxilla is less frequently involved. It is characterized by the presence of well differentiated squamous cells which form islands. Recurrences may rarely occur and probably are related to incomplete excision of the tumor.
Breast cancer is a disease in which certain cells in the breast become abnormal and multiply uncontrollably to form a tumor. Although breast cancer is much more common in women, this form of cancer can also develop in men. In both women and men, the most common form of breast cancer begins in cells lining the milk ducts (ductal cancer). In women, cancer can also develop in the glands that produce milk (lobular cancer). Most men have little or no lobular tissue, so lobular cancer in men is very rare.In its early stages, breast cancer usually does not cause pain and may exhibit no noticeable symptoms. As the cancer progresses, signs and symptoms can include a lump or thickening in or near the breast; a change in the size or shape of the breast; nipple discharge, tenderness, or retraction (turning inward); and skin irritation, dimpling, or scaliness. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a person definitely has breast cancer.In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If breast cancer spreads, cancerous cells most often appear in the bones, liver, lungs, or brain. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers.A small percentage of all breast cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary breast cancers tend to develop earlier in life than noninherited (sporadic) cases, and new (primary) tumors are more likely to develop in both breasts.
The reemergence of a malignant neoplasm after a period of remission.
The presence of aneurysmal polypoidal lesions in the choroidal vasculature. The aneurysmal dilatations, also known as polyps, may be found at subfoveal, juxtafoveal, extrafoveal, peripapillary or even peripheral regions. These polypoidal dilatations may be visible as reddish-orange subretinal nodules during ophthalmoscopic examination. The polypoidal lesions are best detected on indocyanine green angiography (ICGA) and might be associated with a branching vascular network (BVN) of neovascularization. [PMID:24653824]
Increase in mass of the tunica media of the arteries in the pulmonary circulation.
A functional anomaly of the upper motor neuron. The upper motor neurons are neurons of the primary motor cortex which project to the brainstem and spinal chord via the corticonuclear, corticobulbar and corticospinal (pyramidal) tracts. They are involved in control of voluntary movements.\nDysfunction leads to weakness, impairment of fine motor movements, spasticity, hyperreflexia and abnormal pyramidal signs.
Familial precocious puberty in boys usually presents by age 4 with rapid VIRILIZATION and is also characterized by gonadotropin-independent testosterone secretion, low secretion of LUTEINIZING HORMONE, and advanced SPERMATOGENESIS in the testis. Mutations in the LHCGR gene have been identified. OMIM: 176410
A complication during pregnancy; it occurs when the mother is Rh-negative and the infant is Rh-positive. This complication generally does not affect first-born Rh-positive babies. Rh-positive newborn babies from subsequent pregnancies develop complications of Rh incompatibility which include hemolysis, jaundice, enlarged liver and spleen, petechiae, hypotonia, neurologic damage, and heart problems.
An inflammatory lung disease characterized by diffuse interstitial pneumonitis and alveolitis leading to interstitial fibrosis in the absence of an identifiable infectious agent.
An air-filled cystic space within a lung.
Narrowing or constriction of the inner surface (lumen) of a cerebral artery.
Postoperative hemorrhage from an endovascular AORTIC ANEURYSM repaired with endoluminal placement of stent grafts (BLOOD VESSEL PROSTHESIS IMPLANTATION). It is associated with pressurization, expansion, and eventual rupture of the aneurysm.
The reemergence of acute lymphoblastic leukemia after a period of remission.
Bleeding within the subependymal germinal matrix.
Narrowing or constriction of the inner surface (lumen) of the anterior cerebral artery.
Narrowing or constriction of the inner surface (lumen) of the middle cerebral artery.
Narrowing or constriction of the inner surface (lumen) of the posterior cerebral artery.
CD59 glycoprotein (128 aa, ~14 kDa) is encoded by the human CD59 gene. This protein is involved in the inhibition of the assembly of the membrane attack complex in the complement cascade.
Interleukin-1 receptor antagonist protein (177 aa, ~20 kDa) is encoded by the human IL1RN gene. This protein is involved in the inhibition of the interaction between interleukin-1 and its receptor.
The ditosylate salt of lapatinib, a synthetic, orally-active quinazoline with potential antineoplastic activity. Lapatinib reversibly blocks phosphorylation of the epidermal growth factor receptor (EGFR), ErbB2, and the Erk-1 and-2 and AKT kinases; it also inhibits cyclin D protein levels in human tumor cell lines and xenografts. EGFR and ErbB2 have been implicated in the growth of various tumor types.
A isoindolinone derivative and potent inhibitor of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) with chemosensitization and radiosensitization properties. INO-1001 inhibits PARP, which may result in inhibition of tumor cell DNA repair mechanisms and, so, tumor cell resistance to chemotherapy and radiation therapy. PARP enzymes are activated by DNA breaks and have been implicated in the repair of DNA single-strand breaks (SSB).
A thiophene derivative and selective NEUROTRANSMITTER UPTAKE INHIBITOR for SEROTONIN and NORADRENALINE (SNRI). It is an ANTIDEPRESSIVE AGENT and ANXIOLYTIC, and is also used for the treatment of pain in patients with DIABETES MELLITUS and FIBROMYALGIA.
A synthetic derivative of fumagillin with antineoplastic and cytotoxic properties. PPI-2458 irreversibly inhibits the enzyme methionine aminopeptidase type 2 (MetAP2), thereby preventing abnormal cell growth and angiogenesis. PPI-2458 is reported to have a better toxicity profile compared to other agents of its class. (NCI04)
A recombinant protein with megakarypoiesis stimulating activity. AMG 531 mimics endogenous thrombopoietin (TPO), directly binding to and activating the platelet thrombopoietin receptor (TpoR, Mpl, or CD110 antigen), a cytokine receptor belonging to the hematopoietin receptor superfamily. Activation of TPO-R stimulates the proliferation and differentiation of megakaryocytes, resulting in an increase in the production of blood platelets. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=459753&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=459753&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C52183"" NCI Thesaurus)
An orally bioavailable multiple-receptor tyrosine kinase inhibitor. AEE788 inhibits phosphorylation of the tyrosine kinases of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and vascular endothelial growth factor receptor 2 (VEGF2), resulting in receptor inhibition, the inhibition of cellular proliferation, and induction of tumor cell and tumor-associated endothelial cell apoptosis. (NCI05)
An azole derivative of pleuromutilin, an antibacterial agent that inhibits protein synthesis by binding to bacterial ribosomes. Azamulin is a highly selective inhibitor of cytochrome P450 3A4 (CYP3A4).
An orally available inhibitor of CXC chemokine receptor types 1 (CXCR1) and 2 (CXCR2), with potential antineoplastic activity. Upon administration, reparixin allosterically binds to CXCR1 and prevents CXCR1 activation by its ligand interleukin 8 (IL-8 or CXCL8). This may cause cancer stem cell (CSC) apoptosis and may inhibit tumor cell progression and metastasis. CXCR1, overexpressed on CSCs, plays a key role in CSC survival and the ability of CSC to self-renew; it is also linked to tumor resistance to chemotherapy. Inhibition of the IL-8/CXCR1 interaction also potentiates the cytotoxic effect of chemotherapeutic agents. In addition, reparixin inhibits CXCR2 activation and may reduce both neutrophil recruitment and vascular permeability during inflammation or injury.
A quinazoline derivative that inhibits EPIDERMAL GROWTH FACTOR RECEPTOR and HER2 (RECEPTOR, ERBB-2) tyrosine kinases. It is used for the treatment of advanced or metastatic breast cancer, where tumors overexpress HER2.
A synthetic analogue of halichondrin B, a substance derived from a marine sponge (Lissodendoryx sp.) with antineoplastic activity. E7389 binds to the vinca domain of tubulin and inhibits the polymerization of tubulin and the assembly of microtubules, resulting in inhibition of mitotic spindle assembly, induction of cell cycle arrest at G2/M phase, and, potentially, tumor regression. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=257773&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=257773&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C26644"" NCI Thesaurus)
A molecular abnormality indicating rearrangement of the KMT2A gene.
A severe deficiency of spermatogenesis. Chromosome Y deletions are a frequent genetic cause of male infertility. The mode of transmission follows a Y-linked pattern, with incomplete penetrance, but as deletions are often associated with infertility, they generally occur de novo. Molecular diagnosis is made by PCR amplification of STS type sequences (sequence-tagged sites) from the AZFa, b, and c regions. All chromosome Y deletions do not necessarily lead to infertility: firstly, some deletions (especially some partial deletions) do not result in spermatogenesis defects; secondly, among men with severe oligospermia, some can father children without infertility treatment. Finally, when mature spermatozoa are found in the sperm or in the testicles, the infertility problem can be solved with medically assisted procreation techniques. However, there is a risk of transmitting the microdeletion to every male infant.
A somatic dysfunction usually characterized by a rib being held in a position of inhalation such that motion toward inhalation is more free and motion toward exhalation is restricted. Synonyms: inhaled rib, anterior rib, inhalation strain, elevated rib, exhalation restriction.
A synthetic trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine with peripherally selective opioid mu receptor antagonist activity. Alvimopan is a selective and competitive antagonist at mu-opioid receptors, found in myenteric and submucosal neurons and the immune cells of the lamina propria in the human gut. Upon administration, this agent binds to mu-opioid receptors in the gut, thereby reversing opioid-related disturbances in gut motility. Alvimopan is approximately three to nine times more potent than naloxone.
An orally available benzimidazole riboside compound with activity against cytomegalovirus (CMV). Maribavir is a selective ATP competitor of viral UL97 kinase, which is involved in viral nuclear maturation events, such as viral DNA assembly and movement of viral capsids from the nucleus of infected cells. Maribavir has activity against strains of CMV that are resistant to standard anti-CMV agents.
A mesenchymal tumor composed of fibroblastic and histiocytic cells.
A quinuclidine and tetrahydroisoquinoline derivative and selective M3 MUSCARINIC ANTAGONIST. It is used as a UROLOGIC AGENT in the treatment of URINARY INCONTINENCE.
Inability of the brain to properly identify an odors natural smell.
The conversion of a cell from a normal phenotype, which undergoes a limited number of mitotic divisions, into an aberrant phenotype that is immortal and divides indefinitely. Transformed cells no longer retain cell-cycle checkpoints and may ultimately become malignant cancer cells via additional genetic mutations, or damaging environmental events.
Not an aneurysm but a well-defined collection of blood and CONNECTIVE TISSUE outside the wall of a blood vessel or the heart. It is the containment of a ruptured blood vessel or heart, such as sealing a rupture of the left ventricle. False aneurysm is formed by organized THROMBUS and HEMATOMA in surrounding tissue.
Gait apraxia affecting the ability to make walking movements with the legs.
A choroid plexus carcinoma that occurs during childhood.
A recombinant tumor-specific melanoma antigen. Vaccination with recombinant MAGE-3.1 antigen may induce a host immune response against MAGE-expressing cells, resulting in antitumoral T cell-mediated cytotoxicity. MAGE-expressing cells are found in melanoma, non-small-cell lung carcinoma (NSCLC), head and neck squamous cell carcinoma, transitional cell carcinoma of the bladder, and esophageal carcinoma. (NCI04)
A bacterial, fungal, or parasitic abscess that develops in the cerebral hemispheres. Causes include skull trauma, middle ear infection, congenital heart disease, and frontal and ethmoid sinus infection.
Any nerve disorder caused by the entrapment and compression of a nerve.
Inflammation of a superficial vein associated with venous thrombosis (blood clot formation within the vein).
One of 800 terephthalanilides synthesized and tested preclinically in the late 1950's and early 1960's. Chosen in the 1990's for further clinical investigation by the NCI's Project for the Review of Old Drugs because of its structure and activity spectrum.
Uveitis that is usually insidious in onset, bilateral, and can be asymptomatic, most often affecting the anterior uveal tract, including the iris and ciliary body, and can result in long-term complications. It is most commonly associated with certain forms of juvenile idiopathic arthritis, but may occur independent of arthritis.
A genetic disorder characterized by craniosynostosis and fusion of the fingers and toes.
Impairment in the comprehension of speech and meaning of words, both spoken and written, and of the meanings conveyed by their grammatical relationships in sentences. It is caused by lesions that primarily affect Wernicke's area, which lies in the posterior perisylvian region of the temporal lobe of the dominant hemisphere. (From Brain & Bannister, Clinical Neurology, 7th ed, p141; Kandel et al., Principles of Neural Science, 3d ed, p846)
Oral-facial-digital syndrome type I (OFD1) is usually male lethal during gestation and predominantly affects females. OFD1 is characterized by the following features: Oral (lobulated tongue, tongue nodules, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities). Facial (widely spaced eyes or telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft upper lip, micrognathia). Digital (brachydactyly, syndactyly, clinodactyly of the fifth finger; duplicated hallux [great toe]). Kidney (polycystic kidney disease). Brain (e.g., intracerebral cysts, agenesis of the corpus callosum, cerebellar agenesis with or without Dandy-Walker malformation). Intellectual disability (in ~50% of individuals).
A disorder that is caused by the deficiency of a vitamin. The deficiency may result from either suboptimal vitamin intake or conditions that prevent the vitamin's use or absorption in the body. Representative examples include beriberi caused by thiamine deficiency, scurvy caused by vitamin C deficiency, and rickets caused by vitamin D deficiency.
Drug dependence - replaced the term ""drug addiction"" and is defined as a state, psychic and sometimes also physical, resulting from the interaction between a living organism and a drug, characterized by behavioral and other responses that always include a compulsion to take the drug on a continuous or periodic basis in order to experience its psychic effects, and sometimes to avoid the discomfort of its absence. Tolerance may or may not be present. A person may be dependent on more than one drug.
A condition characterized by the presence of multiple diverticuli in the walls of an organ.
A synthetic benzamide derivative. MS-275 binds to and inhibits histone deacetylase, an enzyme that regulates chromatin structure and gene transcription. MS-275 appears to exert dose-dependent effects in human leukemia cells including p21(CIP1/WAF1)-dependent growth arrest and differentiation at low drug concentrations; a marked induction of reactive oxygen species (ROS); mitochondrial damage; caspase activation; and, at higher concentrations, apoptosis. p21(CIP1/WAF1) is an inhibitor of cyclin-dependent kinases; in normal cells, its expression has been associated with cell-cycle exit and differentiation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38294&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38294&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2724"" NCI Thesaurus)
Describes a group of rare familial central nervous system disorders characterised by amyloid deposition in the cerebral blood vessels leading to haemorrhagic and non-haemorrhagic strokes, focal neurological deficits, and progressive cognitive decline eventually leading to dementia. Clinical features depend on the disease type. Most forms of HCHWA (Dutch, Arctic, Piedmont, Iowa, Flemish and Italian) are due to a point-mutation in the APP gene on chromosome 21q21.2, which encodes the beta-amyloid precursor protein. This mutation causes increased accumulation of amyloid-beta protein in the walls of cerebral arteries and capillaries. Only one form of HCHWA, Icelandic type, is due to a mutation in the CST3 gene on chromosome 20p11.2, encoding the precursor protein cystatin C.
Oncocytomas are usually benign tumors that occur in various organs but particularly in the kidneys. Histologic evaluation of renal oncocytomas shows that they are composed entirely of peculiar epithelial cells with granular eosinophilic cytoplasm. Ultrastructural characterization exhibits densely packed cells with mitochondria, which show morphologic differences from those in normal cells. On the average they are larger than those in renal carcinoma cells and their shape is abnormal (summary by Welter et al., 1989).
Epithelial neutrophil activating peptide-78. A 78 amino acid member of the CXC family of chemokines, produced and secreted upon stimulation by interleukin 1 beta or tumor necrosis factor alpha. Stimulates chemotactic migration of neutrophils, monocytes, lymphocytes, and fibroblasts.
Autism spectrum disorder (ASD) is a condition that appears very early in childhood development, varies in severity, and is characterized by impaired social skills, communication problems, and repetitive behaviors. These difficulties can interfere with affected individuals' ability to function in social, academic, and employment settings. People with ASD also have an increased risk of psychiatric problems such as anxiety, depression, obsessive-compulsive disorder, and eating disorders.From as early as 1 to 2 years of age, people with ASD have an impaired ability to interact with other people; they are often more comfortable dealing with objects. Affected individuals have difficulty understanding and using non-verbal social cues such as eye contact, facial expressions, gestures, and body language. Inability to recognize and use these cues makes it hard for affected individuals to understand the feelings of others or communicate their own feelings appropriately. Behavioral signs of ASD, such as reduced eye contact and social interaction, can sometimes be detected before age 2. However, the condition is usually diagnosed between ages 2 and 4, when more advanced communication and social skills, such as learning to play with others, typically begin to develop.Repetitive behaviors in ASD can include simple actions such as rocking, hand-flapping, or repetition of words or noises (echolalia). Affected individuals often dwell on or repeatedly express particular thoughts; this behavior is called perseveration. People with ASD tend to be rigid about their established routines and may strongly resist disruptions such as changes in schedule. They may also have difficulty tolerating sensory stimuli such as loud noises or bright lights.While social and communication difficulties and unusual behaviors define ASD, affected individuals can have a wide range of intellectual abilities and language skills. A majority of people with ASD have mild to moderate intellectual disability, while others have average to above-average intelligence. Some have particular cognitive abilities that greatly surpass their overall level of functioning, often in areas such as music, mathematics, or memory.Some people with ASD do not speak at all, while others use language fluently. However, fluent speakers with ASD often have problems associated with verbal communication. They might speak in a monotone voice, have unusual vocal mannerisms, or choose unusual topics of conversation.Several diagnoses that used to be classified as separate conditions are now grouped together under the diagnosis of ASD. For example, autistic disorder was a term that was used when affected individuals had limited or absent verbal communication, often in combination with intellectual disability. By contrast, Asperger syndrome was a diagnosis formerly applied to affected individuals of average or above-average intelligence who were not delayed in their language development. The broader diagnosis of ASD was established because many affected individuals fall outside of the strict definitions of the narrower diagnoses, and their intellectual and communication abilities may change over time. However, some individuals who were previously diagnosed with one of the subtypes now do not meet all the criteria of the new umbrella diagnosis.
An amide analogue of Trichostatin A studied for potential antineoplastic activity. A-65 inhibits zinc-dependent histone deacetylase, inducing terminal cell differentiation and anti-angiogenic activity. (NCI04)
ABC Transporter Binding involves temporary non-covalent interaction of a molecule through intermolecular physical forces of attraction with the ABC Transporter complex to move the substrate across the plasma cell membrane against a concentration gradient.
A tyrphostin compound inhibiting receptor autophosphorylation by inhibiting protein tyrosine kinase and is used to study receptor function.
The Ah receptor, bHLH/PAS transcription factor, upon binding of an agonist such as 2,3,7,8-tetrachlorodibenzo-p-dioxin translocates into the nucleus and heterodimerizes with the transcription factor ARNT. The Ah receptor/ARNT heterodimer binds to dioxin-responsive elements and alters expression of a number of genes including; CYP1A1, CYP1A2, CYP1B1, and NAD(P)H quinone oxidoreductase. The inactive form of the Ah receptor exists in the cytoplasm as a tetrameric complex composed of the ligand binding subunit, a dimer of the 90-kDa heat shock protein, and X-associated protein 2 (also referred to as AIP or ARA9). (This definition may be outdated - see the DesignNote.)
An oil-water emulsion comprised of QS21 and 3D-MPL used as a vaccine adjuvant to improve T-helper cells and antibody response.
A change in the nucleotide sequence of the ATM gene.
The ataxia telangiectasia-mutated gene (ATM) encodes a protein kinase that acts as a tumor suppressor. ATM activation by ionizing radiation damage to DNA stimulates DNA repair and blocks progression through the cell cycle. Mutation of the ATM gene causes the disease ataxia telangiectasia which involves an inherited predisposition to some cancers. To play this role ATM interacts with a broad network of proteins, including checkpoint factors (chk1, chk2), tumor suppressors (p53 and BRCA), DNA repair factors (RAD50, RAD51, GADD45), and other signaling molecules (c-Abl and NF-kB). In addition to regulating DNA repair and the cell cycle, ATM can also trigger apoptosis in radiation treated cells. (This definition may be outdated - see the DesignNote.)
ATP Hydrolysis is the cleavage of a high-energy phosphate bond of adenosine triphosphate by the addition of water. The energy derived from hydrolysis of ATP is used to drive metabolic reactions including nucleic acid and protein synthesis, to move molecules against concentration gradients (active transport), and to produce mechanical motion (contraction of microfibrils and microtubules).
A vaccine comprised of autologous epithelial ovarian cells infected with ALVAC-hB7.1.
Abasic Site Formation involves the creation of an apurinic or apyrimidinic site resulting from the loss of a purine or pyrimidine residue from DNA.
An intestinal tract lesion where one or more crypts are enlarged and elevated above the surrounding mucosa. Additionally, these crypts often have a slit-shaped luminal opening. Cells are methylene blue positive on whole-mount sections of the intestinal mucosa.
The loss of a fluid from an abscess into the surrounding tissue or body cavity.
Acetaminophen is one of the world's most commonly used drugs, used for the treatment of pain and fever. Like other NSAIDs (non-steroidal anti-inflammatory drugs), acetaminophen has a unique activity profile based in part on its action at its molecular targets, the cyclooxygenase enzymes that produce prostaglandins responsible for pain, fever and inflammation. Until very recently, only two Cox enzymes, Cox-1 and Cox-2, were known to be targets of NSAIDS. Cox-1 is expressed in a constitutive manner throughout most tissues, and plays an essential role in maintaining the integrity of the stomach mucosal lining. Cox-2 is an inducible enzyme whose expression is induced by inflammation. NSAIDS selective for Cox-2 have been developed to avoid the development of ulcers by some non-selective NSAIDs, including aspirin. While these two isoforms were sufficient to account for most NSAIDs pharmacology, the actions of acetaminophen remained hard to explain on the basis of inhibiting Cox-1 and Cox-2 alone, such as its efficacy at reducing pain and fever but lack of anti-inflammatory effects. A novel Cox enzyme isoform encoded by the Cox-1 gene, Cox-3, contains an additional 30-34 amino acids and is expressed selectively in the brain. This insertion alters the pharmacology of the Cox enzyme, making Cox-3 sensitive to selective inhibition by acetaminophen and other drugs that reduce pain and fever but have weak anti-inflammatory activity, explaining the pharmacology of these drugs. Another characteristic of acetaminophen is its liver toxicity when taken at high doses. The target of this toxicity has also been recently been revealed. The nuclear receptor CAR is activated by many different exogenous compounds, including acetaminophen, inducing expression of three cytochrome P450 enzymes that transform acetaminophen into NAPQI, a reactive and toxic metabolite. Blocking CAR activation with an antagonist protects against acetaminophen liver toxicity, suggesting a strategy to treat acetaminophen toxicity. (This definition may be outdated - see the DesignNote.)
Acetyl-CoA is produced in mitochondria through the metabolism of fatty acids and the oxidation of pyruvate to acetyl-CoA. When ATP is needed, this acetyl-CoA can enter the Krebs cycle to drive oxidative phosphorylation. When ATP supplies are abundant, the acetyl-CoA can be diverted to other purposes like energy storage in the form of fatty acids. The biosynthesis of fatty acids from this acetyl-CoA cannot take place directly however, since it is produced inside mitochondria while fatty acid biosynthesis occurs in the cytosol. Also, there is not a mechanism that directly transports acetyl-CoA out of mitochondria. To be transported, the acetyl-CoA must be chemically converted to citric acid using a pathway called the tricarboxylate transport system. Inside mitochondria, the enzyme citrate synthase joins acetyl-CoA with oxaloacetate to make citrate. This citrate is transported from the mitochondria to the cytosol, thus transporting the acetyl-CoA in the form of citrate. Once in the cytosol, the citrate is converted back to oxaloacetate, which is then reduced to malate. Malate can be oxidized to pyruvate by the malic enzyme, with production of NADPH as well, that can contribute to fatty acid biosynthesis. Pyruvate can be reimported back into the mitochondria. Alternatively, malate can be transported itself back into the mitochondria and used to produce NADH once inside mitochondria. (This definition may be outdated - see the DesignNote.)
A carcinoma arising from the ovary. It is characterized by the presence of malignant epithelial cells in a fibrotic stroma. Histologic variants include clear cell, serous, mucinous, and endometrioid adenocarcinofibroma.
A rare adenocarcinoma that arises from the epididymis. It usually presents as a scrotal mass and may be associated with testicular pain.
A rare, benign neoplasm that arises from the vulva It is characterized by the presence of clusters of small glands lined by mucinous epithelial cells. Bartholin duct structures are not present.
A usually benign tumor arising from the breast. It is characterized by the proliferation of cells with myoepithelial differentiation around spaces which are lined by epithelial cells. Rarely, the epithelial and/or myoepithelial cells may undergo malignant transformation. Cases with malignant transformation may follow an aggressive clinical course, including recurrences and local and distant metastases.
An invasive breast carcinoma characterized by the presence of tubular and glandular neoplastic cell structures, admixed with islands of neoplastic cells showing squamous differentiation.
Any substance that inhibits adenylosuccinate synthetase, an enzyme involved in the de novo synthesis of adenosine. A reduction in adenosine interferes with DNA, RNA, and ATP biosynthesis and can cause cell cycle arrest.
Drugs used in combination with other pain drugs to assist or enhance their action.
the ability to nonspecifically stimulate the immune response.
A specific identifiable level (defined qualitatively or quantitatively) of probability of adverse event being caused or associated with the product or procedure administration to a patient.
The heparan sulfate proteoglycan agrin is well known as the key assembly factor of postsynaptic differentiation at the neuromuscular junction (NMJ), but recent data suggest it also plays a direct role in the organization of the cytoskeleton in the skeletal muscle. Signaling through muscle-specific proteins such as muscle specific kinase (MuSK) and or acetylcholine receptor (AchRs)/rapsyn, agrin can activate ubiquitously expressed Rac, Cdc42, and p21-activated kinase (PAK) that are involved in actin polymerization. Agrin also engages signaling pathways of several potent oncogenes (i.e., SFK, ErbB receptors, and cortactin). (This definition may be outdated - see the DesignNote.)
A process in which the hydrogen ion concentration of a solution is decreased, resulting in an increase in alkalinity. Pharmaceuticals that have the capacity to buffer blood or urine solutes are often classified as alkaline agents.
Used topically or systemically for management of metabolic acidosis, improved muscle contraction, and hyper-acidic conditions, Alkalinizing Agent Preparations contain one or more substances with basic properties, such as sodium bicarbonate, sodium citrate, and phosphate salts (potassium phosphate, sodium acid phosphate, and tribasic sodium phosphate). Usually the alkalinizing agent(s) acts as a proton acceptor, neutralizing the acidity of a biologic environment (skin, gastric content, urine, etc.) and raising the pH. (NCI04)
Any substance that inhibits O6-Alkylguanine-DNA alkyltransferase, a DNA repair enzyme that catalyzes the removal of alkyl groups from DNA. Inhibition of O6-Alkylguanine-DNA alkyltransferase increases the effectiveness of DNA alkylating agents.
An ether-linked lysophosphatidylcholine with potential antineoplastic activity. Exhibiting anti-proliferative and immunomodulatory properties, alkyl-phosphocholine compounds modulate cell membrane permeability, phospholipid metabolism, and intracellular growth signal transduction pathways and induce cytotoxic macrophages, cell differentiation, and apoptosis. (NCI04)
An amino acid derivative. As an analog of arginine, amino-arginine competes with the normal substrate arginine and binds to the heme of the NOS as a false substrate, thereby inhibiting endothelial and inducible nitric oxide synthases (eNOS / NOS III and iNOS / NOS II). Arginine is the only physiological substrate for NOS which, in eukaryotic cells, generates NO and L-citrulline from L-arginine and molecular oxygen in a five-electron transfer reaction. This clinical use of amino-arginine is limited due to its epileptogenic properties. (NCI04)
A process that involves the binding of any member of the group of amino acid neurotransmitters, including glutamate, aspartate, serine, glycine and gamma-aminobutyric acid, to their respective receptors. These interactions are involved in neurotransmission.
Natural products containing carbon-phosphorous bonds, so-called C-P compounds, are derivatives of phosphonate and phosphinate with substitution of alkyl group for hydrogen of phosphorus-hydrogen bonds. C-P compounds have been found in many organisms, but only protists and bacteria, mostly Actinobacteria, have biosynthetic capacity. A common reaction in the biosynthetic pathway is C-P bond forming reaction from phosphoenolpyruvate (PEP) to phosphonopyruvate (PnPy) catalyzed by PEP phosphomutase. 2-Aminoethylphosphonate (AEP) is the most abundant C-P compound in the natural world. AEP derivatives include phosphonoprotein, phosphonoglycan, and phosphonolipid. Other known C-P compounds are bioactive substances used in medicine (antibiotics) and agriculture (herbicide) such as fosfomycin, FR-33289, rhizocticin, and bialaphos.
Alzheimer's disease is associated with dense aggregations of proteins in the brain called amyloid plaques that contain beta-amyloid fragments as a primary component. If the development of amyloid plaques is responsible for neurodegeneration in Alzheimer's disease, reduction of beta-amyloid formation may prevent the development and progression of disease symptoms. Beta-amyloid fragments are derived from proteolytic processing of amyloid precursor protein (APP) in neurons, and the subsequent release of fragments into the extracellular space. APP in the ER is cleaved at residue 17 by alpha-secretase protease activity encoded by ADAM-10 and TACE. Beta-secretase activity, recently identified as BACE, cleaves in the N-terminus of the beta-amyloid fragment. Gamma-secretase cuts APP within the transmembrane domain at amino acids 40 and 42, releasing the beta-amyloid fragment containing residues 1-40/42 as well as shorter products such as p3 (residues 17-40/42) that requires alpha-secretase cleavage. The gamma-secretase activity requires the transmembrane protein Presenilin-1 that is itself cleaved into an N-terminal and C-terminal fragment that both are required for gamma-secretase activity. Mutations in presenilin-1 have been genetically associated with familial forms of Alzheimer's disease, further supporting the role of APP processing the development of the disease. Inhibition of the beta- or gamma-secretases may provide a mechanism to treat this disease. Other mechanisms may include altering degradation of beta-amyloid, and the use of vaccines against beta-amyloid to remove aggregates. (This definition may be outdated - see the DesignNote.)
Amyloid Fibril Interaction involves temporary non-covalent binding of a molecule through intermolecular physical forces of attraction with insoluble forms of a secretase-processed metal ion-binding type I cell surface glycoprotein (APP Family) required for endocytosis and basolateral sorting; important in developing synapses, for cell mobility, adhesion, and axonogenesis; and Notch signaling inhibitor, copper homeostasis regulator, transcription activator, and apoptosis enhancer.
Amyloid Resorption Induction involves initiation of activities involved in the breakdown and assimilation of amyloid deposits.
Loss of the balance between stimulation and inhibition of new blood vessel growth. A required early step in cancer growth and metastasis.
A term referring to the presence of tumor emboli or tumor masses within blood vessels (arteries or veins).
An angiosarcoma arising from the skin of the arm following radical mastectomy and resulting lymphedema.
Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. The major regulator of blood pressure homeostasis is the renin-angiotensin system. Angiotensinogen is digested by renin to produce angiotensin I (AGT I). AGT I is an inactive 10 amino-acid peptide that is further degraded to produce angiotensin II by the angiotensin-converting enzyme (ACE). Angiotensin II is the master regulator of blood pressure increase acting on the heart, kidneys and blood vessels. Angiotensin II causes direct constriction of the resistance vessels and stimulation of the adrenal thereby increasing blood volume and sodium absorption. In 2000, Tipnis et al. discovered ACE 2 a second carboxypeptidase that digests angiotensin. ACE is a di-peptidase, cleaving off 2 peptides from the c-terminal end of angiotensin. ACE 2 only cleaves 1 amino acid to produce angiotensin 1-9 (AGT 1-9) which has no identified function at this time. AGT 1-9 is not converted to angiotensin II but further degraded by ACE to AGT 1-7, a vasodilator. It would appear that ACE 2 inhibits the formation of angiotensin and reduces blood pressure increases. Crackower et al determined that ace2 -/- mice suffered significant heart defects at 6 months. Further deletion of ACE resulted in restored cardiac functions. (This definition may be outdated - see the DesignNote.)
Ang II binding to AT1-R triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to Pyk2 and to the small G protein Rac1 but not Cdc42. In turn, Rac1 activates a small G protein-activated kinase whose identity is still controversial, but which has been suggested to be PAK1. Finally, the JNK cascade, including MEKK1, SEK1, and JNK, is activated, causing induction of the c-Jun gene via binding of ATF2 and c-Jun heterodimer to the junTRE2 site. Ang II is closely involved in cardiac remodeling by stimulating synthesis of extracellular matrix proteins. It was recently found that expression of fibronectin by Ang II is transcriptionally regulated by AP-1 complex in cardiac fibroblasts. The collagenase gene, containing AP-1 sites, is also regulated by AP-1 components, including c-Jun. AP-1 activity is also enhanced in Ang II-induced cardiac hypertrophy. Expression of ANF is regulated by AP-1 components. (This definition may be outdated - see the DesignNote.)
A process that involves the non-covalent binding of angiotensin II to an angiotensin receptor family protein. These interactions are involved in signaling that modulates both blood vessel constriction and blood pressure.
Anion Transporter Binding involves temporary non-covalent interaction of a molecule through intermolecular physical forces of attraction with an anion transporter protein that moves the bound ion carrying a negative charge across a cell membrane with or against a concentration gradient.
One of the key causes of anthrax virulence is the action of three specific factors produced by the bacterium Bacillus anthracis. Even with successful antibiotic treatment, anthrax toxins can remain in the circulation and cause lethality. The toxins produced by anthrax bacteria are lethal factor (LF), protective antigen (PA) and edema factor (EF). The entry of toxin into cells begins with the recognition of a cellular receptor in the plasma membrane by PA. Proteolytic cleavage of cell-bound PA creates a smaller fragment that then multimerizes into a pore-like structure in the plasma membrane. The LF and EF proteins bind to the PA pre-pore, followed by internalization of the entire structure through receptor-mediated endocytosis. In the endosomal compartment, the acidic pH causes a conformational change that inserts PA fragments and releases LF and EF into the cytoplasm. In the cytoplasm, LF acts as a protease that cleaves MAP kinase kinase (MAPKK 1 and MAPKK 2), inhibiting pathways that rely on this kinase family and causing cell death. Edema factor is an adenylate cyclase that inhibits the immune response, including phagocytosis by macrophages. (This definition may be outdated - see the DesignNote.)
An agent that inhibits metastasis by interfering with the binding of tumor cells to each other or to endothelial cells.
An immunoconjugate of the humanized monoclonal antibody hP67.6 chemically linked to a bacterial toxin, N-acetyl-gamma calicheamicin, by 4-acetylphenylacetic acid, with antileukemic property. The monoclonal antibody portion specifically binds to CD33 antigen, a cell surface antigen expressed on normal non-pluripotent hematopoietic stem cells as well as over-expressed on myelogenous leukemia cells. Upon internalization, calicheamicin, an enediyne class antibiotics, is released from the conjugate by hydrolysis, and binds in a sequence specific manner to the minor groove of DNA. Thereby leads to breakage of double-stranded DNA and consequently resulting in cell death.
An immunoconjugate of the anti-dopamine-b-hydroxylase monoclonal antibody covalently linked to the ribosome-inactivating protein (RIP) saporin derived from Saponaria officinalis. The monoclonal antibody component recognizes and attaches to the membrane-associated antigen, dopamine-b-hydroxylase, resulting in the conjugate being internalized by receptor-mediated endocytosis. The saporin toxin is then released from the complex, and binds to ribosomal subunits, thereby halts protein synthesis, and results in cell death. This immunoconjugate targets the dopamine-beta-hydroxylase enzyme localized on adrenergic nerves in the brainstem particular medulla and pons, thereby could be used to study neurodegenerative disorders and/or address fundamental neurobiological questions.
A vaccine made of antibodies that see other antibodies as the antigen and bind to it. Anti-idiotype vaccines can stimulate the body to produce antibodies against tumor cells.
A substance that blocks the activity of a progestin.
Glutamine is converted to glutamate by glutaminase, or several other enzymes, by the removal of the amide nitrogen. Proline is first converted to a Schiff base and then converted by hydrolysis to glutamate-5-semialdehyde. All of these changes occur on the same carbon. Arginine and histidine contain 5 adjacent carbons and a sixth carbon attached through a nitrogen atom. The catabolism of these amino acids is thus slightly more complicated than glutamine or proline. Arginine is converted to ornithine and urea. Ornithine is further transaminated to produce glutamate-5-semialdehyde. Glutamate-5-semialdehyde is converted to glutamate. Tetrahydrofolate is the cofactor in the final step converting histidine to glutamate. Transamination or deamination of glutamate produces a-ketoglutarate which feeds into the citric acid cycle. (This definition may be outdated - see the DesignNote.)
A neurofibroma characterized by the presence of cellular pleomorphism.
An autologous therapeutic vaccine for the treatment of acute myelogenous leukemia. This vaccine is prepared from blood samples of patients following their first relapse. Tumor cells extracted from blood sample are modified with hapten, a process that makes the cells appear foreign to the patient's body and results in stimulating immune response against the cancer.
An autologous-cell vaccine for melanoma.
A vaccine consisting of autologous cancer cells modified with the hapten, Dinitrophenyl. The treatment program consists of multiple intradermal injections of irradiated DNP-modified autologous tumor cells mixed with bacillus Calmette-Guerin.
A process that involves the binding of an antigen to the transmembrane B cell receptor, an IgD molecule. These interactions are involved in signaling the B cell to be activated and to participate in immune function.
Physical interactions between integrin alpha4beta1 heterodimer expressed on B cells and counter receptors on stroma cells are key mediators of the survival of normal and malignant B cells. Recent data indicate that integrin stimulation increases FBI-1, XIAP, survivin, and CCT4 expression but inhibits Requiem, c-Fos, and caspase 3 and 7 induction. (This definition may be outdated - see the DesignNote.)
A change in the nucleotide sequence of the BRAF gene.
A mutation that is typically a heritable, permanent change in the nucleotide sequence of the BRCA1 gene. Single nucleotide substitutions and small deletions or insertions (1-20 bases) account for the majority of mutations in the BRCA1 gene. Approximately 75% of these alterations result in a truncated form of the breast cancer type 1 susceptibility protein. Mutations in the BRCA1 gene predispose individuals to breast and ovarian cancers.
A mutation that is typically a heritable, permanent change in the nucleotide sequence of the BRCA2 gene. Single nucleotide substitutions and small deletions or insertions (1-20 bases) account for the majority of mutations in the BRCA2 gene. Most of these alterations result in a truncated form of the breast cancer type 2 susceptibility protein. Mutations in the BRCA2 gene predispose males to breast cancer.
BTG2 is found to be one of the immediate early genes up-regulated by neural growth factor (NGF) and epidermal growth factor (EGF). Its transcriptional level is also up-regulated by p53, gamma radiation, adriamycin, and UV treatment of cells. BTG seems to be important for the cell cycle progression as BTG2 is preferentially expressed in quiescent cells. Over-expression of BTG2 decreases the growth of NIH3T3 cells and induces neuronal differentiation and prevention apoptosis of PC12 cells. Molecularly, BTG2 expression induces hypophosphorylation of RB and G1 arrest which could be rescued by overexpression of cyclin D1. BTG1 and BTG2 interact with PRMT1 (predominant cellular arginine N-methyltransferase) and increase PRMT1 methyltransferase activity. Box C domain in BTG1 and 2 are responsible for the interaction. Box C domain alone acts as a dominant negative which blocks PRMT1 activity. PRMT1 activity is essential for NGF induced PC12 differentiation, and blocking PRMT1 by Box C domain of BTG1 or 2 induces apoptosis. In addition, BTG2 and HoxB9 interaction enhances the transcription of Hoxb9. Lastly, association of BTG2 and BTG1 with Caf1 is also reported to modulate transcriptional activity of CAF1. (This definition may be outdated - see the DesignNote.)
A recombinant human prostate-specific antigen (PSA) protein expressed by baculovirus. Baculovirus-derived PSA protein is cross-reactive with native PSA, and has potential use in immunotherapy for prostate cancer. (NCI04)
A vaccine consisting of recombinant carcinoembryonic antigen (CEA) produced by a baculovirus expression system with potential antineoplastic activity. Vaccination with baculovirus CEA protein vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against CEA positive cells, resulting in decreased tumor growth. CEA is overexpressed in several cancer cell types, including gastrointestinal, breast, and non-small cell lung cancers. (NCI04)
Interchanges of genetic material among different chromosomes following the breaking off of pieces of chromosomes such that the total chromosome composition may still contain all of the genetic material.Balanced Chromosomal Rearrangement.
A carcinoma that arises from the Bartholin gland and is characterized by the presence of islands of uniform malignant cells forming cribriform patterns.
A rare, benign neoplasm that arises from the Bartholin gland and is characterized by the presence of clustered glands and tubules lined by mucin-secreting epithelial cells.
A rare, benign neoplasm that arises from the Bartholin gland and is characterized by the presence of a fibromuscular stroma and glands lined by mucin-secreting epithelial cells, arranged in a lobular architecture.
A carcinoma that arises from the Bartholin gland and is characterized by the presence of malignant glandular epithelial cells and malignant squamous epithelial cells.
A rare neuroendocrine carcinoma that arises from the Bartholin gland and is characterized by the presence of malignant small cells and high mitotic activity.
A carcinoma that arises from the Bartholin gland and is characterized by the presence of malignant squamous epithelial cells.
A rare carcinoma that arises from the Bartholin gland and is characterized by the presence of malignant urothelial-type epithelial cells.
A solid/multicystic ameloblastoma with follicular pattern in which the odontogenic epithelial islands are composed of uniform basaloid cells.
An aggressive variant of cervical squamous cell carcinoma characterized by the presence of nests of malignant basaloid squamous cells with scant amount of cytoplasm.
Base-Base Mismatch results from mutagenic factors that induce chemical modification of DNA bases so that pairing between specific bases on complementary DNA strands is eliminated causing mispairing.
A vaccine consisting of replication-defective recombinant adenovirus that encodes for Bcl-Xs with potential antineoplastic activity. Vaccination with Bcl-Xs adenovirus vaccine induces apoptosis in Bcl-2 and Bcl-XL positive cancer cells, resulting in decreased tumor growth while leaving normal cells unaffected. Bcl-Xs block the function of the protooncogenes Bcl-2 and Bcl-XL which are overexpressed in a variety of solid tumors and promote cancer cell survival by inhibiting apoptosis. (NCI04)
A neoplasm that arises from the cervix and is characterized by the presence of benign epithelial and benign mesenchymal elements. This category includes adenofibroma and adenomyoma.
A cytologically benign smooth muscle neoplasm that arises from the uterine corpus and has metastasized to the lungs, abdomen, or lymph nodes. It usually presents in women with a history of benign uterine leiomyomas that have been surgically removed years before the extrauterine neoplasm spread.
A benign neoplasm that arises from the vulva and is characterized by the presence of epithelial cells forming nests and tubules in a fibrotic stroma. It may recur locally and complete excision is recommended.
A non-metastasizing neoplasm that arises from the ovary. It is characterized by a predominance of clear and hobnail benign epithelial cells.
A non-metastasizing neoplasm that arises from the ovary and is characterized by the presence of neoplastic epithelium that resembles the epithelium of the endocervix or gastrointestinal tract. It includes mucinous adenofibroma, mucinous cystadenofibroma, and mucinous cystadenoma.
A non-metastasizing neoplasm that arises from the ovary and is characterized by the presence of neoplastic epithelial cells that resemble urothelial cells.
A mature monodermal teratoma that arises from the ovary and is characterized by the presence of benign, thyroid-type tissues.
A neoplasm that arises from the vagina and is characterized by the proliferation of nests of benign melanocytes.
A non-metastasizing neoplasm that arises from the vagina and is characterized by the presence of benign epithelial and benign mesenchymal elements.
A non-metastasizing, well circumscribed neoplasm that arises from the vagina and is characterized by the presence of a predominant benign mesenchymal component and benign glandular or squamous epithelial cells.
A synthetic vaccine combining the peptide antigens of two proteins, ras oncoprotein and tumor suppressor p53. (NCI04)
Lipopolysaccharide (LPS) from XX bacteria induces a wide range of inflammatory responses, including the response of alveolar macrophages to bacteria in the lungs. CD14 and the Toll-like receptor TLR4 are activated by LPS, initiating a signaling cascade that activates PI3 kinase and increases synthesis of the inositol phosphate PIP3. PIP3 activates the inositol phosphate dependent protein kinase PDK1, which activates AKT (protein kinase B). One of the key actions of AKT is to block apoptosis. AKT phosphorylation of NF-kB promotes the survival and activation of macrophages responding to LPS. Another substrate of AKT is the protein kinase Gsk3-beta. AKT phosphorylates and deactivates Gsk3-beta. Non-phosphorylated Gsk3-beta is active and phosphorylates beta-catenin, leading to its degradation in the ubiquitin dependent proteasome pathway. Stimulation by LPS causes the accumulation of beta-catenin in the nucleus and the activation of genes in concert with the transcription factor LEF1. This pathway is probably not restricted to alveolar pathway, but leads to the activation of beta-catenin dependent genes by LPS in other cells as well. Other pathways regulate this pathway also, such as the modulation of PI3 kinase activity by ceramide and the inhibition of Gsk3-beta activity by the Wnt/frizzled/disheveled (DSH) pathway. (This definition may be outdated - see the DesignNote.)
A change in the nucleotide sequence of the CTNNB1 gene.
Cyclin-dependent kinase 5 (cdk5), a multi-functional kinase, and its neuron-specific activator p35 are required for neurite outgrowth and cortical lamination. Proteolytic cleavage of p35 produces p25, which accumulates in the brains of patients with Alzheimer's disease. Conversion of p35 to p25 causes prolonged activation and mislocalization of cdk5 and the hyperphosphorylates tau, leading to the formation of paired helical filaments and promotion of apoptosis. In cultured primary cortical neurons, excitotoxins, hypoxic stress and calcium influx induce the production of p25. In fresh brain lysates, addition of calcium can stimulate cleavage of p35 to p25. Specific inhibitors of calpain1 effectively inhibit the calcium-induced cleavage of p35. In vitro, calpain1 directly cleaves p35 to release a fragment with relative molecular mass 25,000. Application of the amyloid beta-peptide A beta induces the conversion of p35 to p25 in primary cortical neurons. Inhibition of cdk5 or calpain activity reduces cell death in A beta-treated cortical neurons. These observations indicate that cleavage of p35 to p25 by calpain may be involved in the pathogenesis of Alzheimer's disease. GSK3B also phosphorylates tau but does not induce hyperphosphorylation in response to calpain activating stimuli. Additionally, down-regulation or inhibition of PP2A increases the hyper-phosphorylation of tau. (This definition may be outdated - see the DesignNote.)
The motor defects of Parkinson's disease are related to the loss of dopaminergic neurons in specific brain regions. Examination of these neurons in diseased tissue has revealed the presence of Lewy bodies, dense aggregates that include the protein alpha-synuclein. A genetic basis for most cases of Parkinson's disease has not yet been identified, but mutations in alpha-synuclein have been associated with at least one rare form of the disease, and mutations in another protein, the parkin gene, are associated with another inherited form of Parkinson's disease. Parkin is found in Lewy bodies along with alpha-synuclein and the parkin protein is an enzyme, an E3 ubiquitin ligase. This ligase tags specific proteins in normal cells with ubiquitin, targeting them for destruction in the proteasome. One of the proteins that parkin normally targets for destruction is a specific O-glycosylated form of alpha-synuclein. Failure of parkin-mediated degradation of alpha-synuclein may be a key factor leading to the death of dopaminergic neurons. Another substrate of parkin is a GPCR-like protein called Pael-R that accumulates in the ER of affected cells and may cause neuronal cell death. The involvement of Parkin and alpha-synuclein mutations in genetic forms of Parkinson's suggests that failure of ubiquitination and protein degradation may be causative in other forms of Parkinson's. Questions remaining include the cause of the lack of effective ubiquitination in individuals lacking obvious genetic defects in this pathway and how to use this knowledge of ubiquitination and protein degradation in Parkinson's disease to identify therapeutic strategies. (This definition may be outdated - see the DesignNote.)
Many different peptides act as signaling molecules, including the proinflammatory peptide bradykinin, the protease enzyme thrombin, and the blood pressure regulating peptide angiotensin. While these three proteins are distinct in their sequence and physiology, and act through different cell surface receptors, they share in a common class of cell surface receptors called G-protein coupled receptors (GPCRs). Other polypeptide ligands of GPCRs include vasopressin, oxytocin, somatostatin, neuropeptide Y, GnRH, luteinizing hormone, follicle stimulating hormone, parathyroid hormone, orexins, urotensin II, endorphins, enkephalins, and many others. GPCRs form a broad and diverse gene family that responds not only to peptide ligands but also small molecule neurotransmitters (acetylcholine, dopamine, serotonin and adrenaline), light, odorants, taste, lipids, nucleotides, and ions. The main signaling mechanism used by GPCRs is to interact with G-protein GTPase proteins coupled to downstream second messenger systems including intracellular calcium release and cAMP production. The intracellular signaling systems used by peptide GPCRs are similar to those used by all GPCRs, and are typically classified according to the G-protein they interact with and the second messenger system that is activated. For Gs-coupled GPCRs, activation of the G-protein Gs by receptor stimulates the downstream activation of adenylate cyclase and the production of cyclic AMP, while Gi-coupled receptors inhibit cAMP production. One of the key results of cAMP production is activation of protein kinase A. Gq-coupled receptors stimulate phospholipase C, releasing IP3 and diacylglycerol. IP3 binds to a receptor in the ER to cause the release of intracellular calcium, and the subsequent activation of protein kinase C, calmodulin-dependent pathways. In addition to these second messenger signaling systems for GPCRs, GPCR pathways exhibit crosstalk with other signaling pathways including tyrosine kinase growth factor receptors and map kinase pathways. Transactivation of either receptor tyrosine kinases like the EGF receptor or focal adhesion complexes can stimulate ras activation through the adaptor proteins Shc, Grb2 and Sos, and downstream Map kinases activating Erk1 and Erk2. Src kinases may also play an essential intermediary role in the activation of ras and map kinase pathways by GPCRs. (This definition may be outdated - see the DesignNote.)
A linked series of non-equivalent biochemical interactions and enzymatic reactions, and/or a linked series of biochemical processes.
A chemical process, typically mediated by an enzyme, in which one or more substances (a substrate) are transformed by covalent modification into another substance(s) (a product) or in which the state of a substance is transformed.
Studies of the role of non-viral biological agents as factors or cofactors in the etiology of human and animal cancer.
A non-viral expression system using multifunctional plasmid DNA to deliver disease-specific to immune cells and encode peptides/proteins to modulate various diseases. (NCI04)
A protein tyrosine kinase inhibitor that competitively inhibits epidermal growth factor receptor kinase activity. (NCI)
A sulfur mustard vesicant that had application in chemical warfare, treatment of psoriasis and has been studied as an alkylating agent in cancer therapy. (NCI)
Location on a DNA strand where the phosphate backbone is intact but the nitrogenous base has been lost from both DNA strands.
A rare morphologic variant of bladder adenocarcinoma characterized by the presence of malignant glandular epithelial cells and clear cells forming a diffuse pattern.
A neoplasm of the bladder in which the epithelial cells grow downward into the underlying supportive tissue, which often causes hematuria.
A rare morphologic variant of bladder adenocarcinoma characterized by the presence of malignant glandular epithelial cells and clear cells forming a papillary pattern.
A rare, benign neoplasm of bladder that is composed of papillary cores with overlying histologically benign squamous epithelium.
A rare morphologic variant of bladder carcinoma characterized by the presence of malignant glandular epithelial cells and clear cells forming a tubulo-cystic pattern.
A transitional cell carcinoma of the urinary bladder that arises from the urachal epithelium.
The loss of any normal body fluid into the surrounding tissue or body cavity.
An agent that antagonizes bombesin, an endogenous neurotransmitter found in many animals, and affects smooth muscle, gastrin secretion, and renal function.
Osteoblasts mineralize bone matrix by promoting hydroxyapatite crystal formation and growth in the interior of membrane-limited matrix vesicles (MVs) and by propagating the crystals onto the collagenous extracellular matrix. Two osteoblast proteins, tissue-nonspecific alkaline phosphatase (TNAP) and plasma cell membrane glycoprotein-1 (PC-1) are involved in this process. In the bone matrix, PC-1 is the major producer of PPi, which in turn has an inhibitory effect on hydroxyapatite deposition. TNAP has a positive influence on mineralization primarily by controlling the size of the inhibitory pool of PPi through its inorganic pyrophosphatase activity. TNAP also generates Pi by using NTPs and PPi as substrates, but other more major sources of Pi e.g., intestinal absorption, are likely to contribute the bulk of the Pi needed for hydroxyapatite deposition. (This definition may be outdated - see the DesignNote.)
A neoplasm of low malignant potential arising from the fallopian tube. It is characterized by the presence of glandular or cystic spaces which contain atypical glandular epithelial cells resembling endometrial cells. There is no evidence of stromal invasion.
A neoplasm of low malignant potential arising from the fallopian tube. It is characterized by an atypical proliferation of mucinous-type epithelial cells without evidence of stromal invasion.
A rare epithelial tumor arising from the fallopian tube without definitive morphologic characteristics of malignancy. This category includes borderline mucinous and serous neoplasms and borderline endometrioid tumor.
A neoplasm of low malignant potential arising from the fallopian tube. It is characterized by an atypical proliferation of serous-type epithelial cells without evidence of stromal invasion.
An epithelial neoplasm with low malignant potential affecting the ovary. It is characterized by the presence of atypical glands and/or cystic spaces lined with clear or hobnail cells.
An epithelial neoplasm with low malignant potential affecting the ovary. It is characterized by the presence of atypical glands and/or cystic spaces lined with clear or hobnail cells. The cells display nuclear atypia and prominent nucleoli. There is no invasion of the ovarian stroma by the atypical cells.
An epithelial neoplasm with low malignant potential affecting the ovary. It is characterized by the presence of prominent cystic spaces lined with clear or hobnail cells. There is no evidence of stromal invasion.
An epithelial neoplasm with low malignant potential affecting the ovary. It is characterized by the presence of clear or hobnail cells. In some cases, the cells may display nuclear atypia and prominent nucleoli. When such cells are present, they remain confined to the glands. There is no evidence of stromal invasion.
An epithelial neoplasm that arises from the ovary characterized by the presence of glandular or cystic spaces which contain atypical glandular epithelial cells resembling endometrial cells. The surrounding ovarian stroma is fibrotic. There is no evidence of stromal invasion.
A low grade mucinous epithelial neoplasm arising from the ovary. It is characterized by an atypical proliferation of mucinous-type epithelial cells without evidence of stromal invasion. The mucinous epithelial cells may be of intestinal or endocervical type.
A neoplasm of low malignant potential arising from the ovary. It is characterized by the proliferation of neoplastic epithelial cells that resemble endocervical epithelial cells. There is no evidence of stromal invasion.
A neoplasm of low malignant potential arising from the ovary. It is characterized by the proliferation of neoplastic mucinous epithelial cells that resemble intestinal epithelial cells. There is no evidence of stromal invasion.
A low malignant potential adenofibroma arising from the ovary. It is characterized by an atypical epithelial hyperplasia. The epithelial cells are of serous type. There is no evidence of stromal destructive invasion.
A neoplasm of low malignant potential arising from the ovary. It is characterized by the presence of cystic spaces which are lined by atypical serous epithelial cells. The surrounding ovarian stroma is fibrotic. There is no evidence of stromal invasion.
A neoplasm of low malignant potential arising from the ovary. It is characterized by the presence of papillary proliferations of atypical serous epithelial cells and a cystic component. There is no evidence of stromal invasion.
A neoplasm of low malignant potential arising from the ovary. It is characterized by the presence of papillary proliferations that contain atypical serous epithelial cells in the outer surface of the ovary. There is no evidence of stromal invasion.
A low grade ovarian epithelial neoplasm characterized by the presence of neoplastic serous epithelial cells, atypia, and microinvasion of the ovarian stroma.
An ovarian epithelial neoplasm that resembles the transitional cell neoplasms found in the urinary tract. It is characterized by the presence of atypia and absence of stromal invasion.
A rare borderline tumor that arises from the uterine ligament. The majority of the reported cases are serous cystic tumors.
Agents used in Boron Neutron Capture Therapy, a type of radiotherapy, as boron (boron-10) carriers.
A morphologic variant of embryonal rhabdomyosarcoma arising from the vagina. It is characterized by the formation of a cambium layer in the affected tissue and polypoid nodules within an abundant myxoid stroma.
The neuromuscular junction communicates action potentials from motor neurons across a synapse to skeletal muscle. When an action impulse arrives at the neuromuscular junction, the entry of calcium through voltage-gated calcium channels causes synaptic vesicles to fuse with the presynaptic plasma membrane and release the neurotransmitter acetylcholine into the synaptic cleft. Acetylcholine diffuses across the cleft and binds to muscle acetylcholine receptors, causing depolarization and an action potential that travels throughout the length of the muscle cell triggering muscle contraction. The release of neurotransmitter at the synapse involves the fusion of synaptic vesicles with the neuronal plasma membrane and requires several proteins that act together to form a synaptic fusion complex. These proteins, collectively called SNARE proteins, include SNAP-25, syntaxin, and synaptobrevin. Homologs of these proteins are also involved in membrane fusion in other aspects of vesicle trafficking. Synaptobrevin (also called VAMP2) is localized at the synaptic vesicle membrane, while SNAP-25 and syntaxin are associated with the plasma membrane. Calcium release causes the formation of a complex, bringing the synaptic vesicle in close proximity with the plasma membrane and allowing fusion of the membranes. Biological toxins often disrupt nervous function, particularly the action of motor neurons. Botulinum toxin, synthesized by the bacteria Clostridium botulinum, is one of the most potent toxins known and acts by blocking neurotransmitter release at the neuromuscular junction. Botulinum toxin is a protein composed of two subunits joined by a disulfide bond, a 100 kD heavy subunit and a 50 kD light subunit that is a protease. There are seven serotypes of botulinum with distinct toxins. Tetanus toxin is similar in structure and in mechanism of action to botulinum toxin. The toxins can be absorbed in the intestine to travel in the blood to its site of action, at the neuromuscular junction. At the synapse botulinum toxin binds to the presynaptic membrane, and large subunit mediates internalization into the neuron through endocytosis. Once inside the neuron, the light chain is translocated across the vesicular membrane to act as a protease on cytoplasmic substrates. The targets of the toxin protease include the components of the synaptic fusion complex. Tetanus toxin and botulinum B, D, F and G toxins degrade synaptobrevin, while botulinum A, C and E toxins cleave SNAP-25. Syntaxin is also targeted by serotype C toxin. Destruction of these proteins by botulinum toxin prevents vesicular fusion in response to action potentials, blocking the release of acetylcholine. This blockade of communication between the nervous system and skeletal muscle can cause paralysis and can lead to death if the paralysis is severe enough to prevent breathing. In addition to acting as a toxin during botulism infection, botulinum toxin is also now being used as a pharmaceutical. Careful administration of very small doses of toxin can restrict its action locally to reduce overactive muscles, such as those involved in twitching of the eyes. Relaxing the muscles around the eyes can also reduce wrinkles in the eye region, leading to cosmetic use of this potent bacterial toxin. The potency of botulinum toxin has also caused concern that it could be used as a biological weapon, creating interest in the identification of inhibitors of this toxin. (This definition may be outdated - see the DesignNote.)
A substance isolated from the pituitary glands of cattle which contains a variety of proteins, hormones, and growth factors. Bovine pituitary extract is used in research as a mitogenic supplement in the cell culture of various epithelial and endothelial cell lines. (NCI04)
An invasive adenocarcinoma of the breast usually affecting post-menopausal women, characterized by extensive spindle cell metaplasia of the neoplastic glandular cells.
A breast hamartoma characterized by the presence of brown fat that contains entrapped glands.
An uncommon variant of breast adenosis characterized by the presence of irregularly shaped glands, epithelial cells with eosinophilic cytoplasm, and prominent myopepithelial cells. Mild atypia may be present.
A benign diffuse vascular proliferation in the breast. It is characterized by the formation of capillary-sized and cavernous vascular spaces.
A neoplastic process characterized by the proliferation of spindle to cuboidal myoepithelial cells in and around small breast ducts exhibiting cytologic atypia and mitotic activity.
A Burkitt lymphoma that arises from the breast. It usually affects pregnant or lactating women and presents with bilateral breast involvement and breast swelling.
An invasive ductal breast carcinoma, not otherwise specified, characterized by increased levels of human beta-chorionic gonadotropin in the serum. Morphologic evidence of choriocarcinomatous differentiation is rare.
A very rare primary malignant tumor of the breast, characterized by an invasive breast carcinoma that co-exists with a melanoma component. The vast majority of melanotic tumors that affect the breast are metastatic melanomas that originate in extra-mammary sites.
An invasive breast adenocarcinoma characterised by the presence of non-neoplastic stromal osteoclastic giant cells. The carcinomatous component is usually an invasive ductal carcinoma, although all other breast adenocarcinoma subtypes have also been described. The prognosis depends on the characteristics of the adenocarcinomatous component, and is not related to the presence of the giant cells.
An invasive breast adenocarcinoma characterized by the presence of tall columnar neoplastic cells that contain intracytoplasmic mucin. Grossly, cystic changes are not identified.
A diffuse large B-cell lymphoma that arises from the breast. It is the most common type of primary breast lymphoma.
A benign, well circumscribed neoplasm that is located within the lumen of a duct in the breast parenchyma. It is characterized by the presence of glandular structures at the periphery and fibrous tissue at the center of the tumor.
A benign or malignant biphasic neoplasm that arises from the breast parenchyma. It is characterized by the presence of an epithelial and a mesenchymal (stromal) component. The typical examples are fibroadenoma and phyllodes tumor.
A follicular lymphoma that arises from the breast as a primary tumor.
A usually benign neoplasm that arises from the breast. It presents as a single, firm, and painless mass. It is characterized by the presence of neoplastic cells with eosinophilic granular cytoplasm.
A hemangiopericytoma arising from the breast.
A multinodular intermediate fibroblastic neoplasm arising from the breast. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes, and plasma cells.
A poorly differentiated neuroendocrine carcinoma that arises from the breast. It is characterized by the presence of large neuroendocrine cells and high mitotic activity.
A well-circumscribed benign smooth muscle neoplasm arising from the breast. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An invasive breast adenocarcinoma characterized by the presence of tall columnar neoplastic cells that contain intracytoplasmic mucin. Grossly, cystic changes are identified.
A benign or malignant tumor that arises from the breast and originates from or is composed of myoepithelial cells. Representative examples include adenomyoepithelioma, myoepitheliosis, and malignant myoepithelioma.
A myofibroblastoma occurring in the breast of both women and men. It presents as a slowly growing mass.
A breast hamartoma characterized by the predominance of a smooth muscle component.
A rare, benign and well circumscribed neoplasm that arises from the breast. It is characterized by the proliferation of epithelial and myoepithelial cells surrounded by chondroid stroma.
A benign or malignant mesenchymal neoplasm of the breast. Representative examples of benign mesenchymal neoplasms include leiomyoma, lipoma, and myofibroblastoma. Representative examples of malignant mesenchymal neoplasms include angiosarcoma, leiomyosarcoma, and liposarcoma.
Expression of Fas-Ligand by T cells can induce apoptosis through interaction with Fas on the target cell. A target of Fas-mediated apoptosis is the B cell. B cells that are not activated by antigen, bystander B cells, can interact through CD40 with the CD40 ligand on T cells. The CD40-CD40L interaction induces Fas expression by bystander B cells, and the interaction of Fas with the T cell Fas-Ligand, followed by B cell apoptosis. B cells that are activated by antigen binding and that interact with the T cell receptor through the B cell MHC II appear to become resistant to Fas-mediated apoptosis, survive and proliferate. IL-4 also appears to confer B cell resistance to Fas-mediated apoptosis. The induction of apoptosis in non-antigen stimulated B cells may prevent B cells from proliferating inappropriately and failure of this mechanism may be involved in autoimmune disorders and B cell lymphomas. (This definition may be outdated - see the DesignNote.)
A point mutation of the KIT gene that originated in non-germline cells.
A molecular abnormality indicating the presence of an abnormally high level of the mast/stem cell growth factor receptor Kit protein.
A cytogenetic abnormality that refers to the translocation of the MYC gene to a new chromosomal location.
Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known. (This definition may be outdated - see the DesignNote.)
Expression of a fusion protein that results from an inversion or translocation, which involves the human genes CBFB and MYH11 and is associated with acute myeloid leukemias.
An immunoglobulin derived from the single-chain antigen-binding domain (sFv) of the monoclonal antibody CC-49 with potential antineoplastic activity. The parent monoclonal antibody CC-49 binds to the tumor-associated glycoprotein TAG-72 with high affinity, recognizing many tumor cell types that express TAG-72. Because of its single-chain structure, CC-49/218 sFv may exhibit a longer half-life than the parent monoclonal antibody CC-49; 218 represents the linker sequence that helps reduce aggregation and proteolysis of this agent. (NCI04)
A molecular genetic abnormality indicating the presence of multiple copies of the CCND1 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the CCNE1 gene.
Eosinophils are a key class of leukocytes involved in inflammatory responses, including allergic reactions in skin and airway. The eosinophil response in inflammation is absent in mice lacking CCR3, indicating the key role of this G protein coupled receptor in inflammation and allergic responses. Eotaxin is a chemokine ligand for CCR3 that recruits eosinophils to the site of inflammation and activates them. Other chemokine ligands of CCR3 include eotaxin-2, MCP-3, MCP-4, and RANTES. Multiple signaling pathways activated by CCR3 participate in the inflammatory response of eosinophils. Eotaxin stimulates intracellular calcium release, production of reactive oxygen species, and changes in actin polymerization through a pertussis sensitive pathway. Rho is a G protein that activates ROCK, a protein kinase. Rho and ROCK regulate actin stress fiber formation and are required for eosinophil chemotaxis. Map kinase pathways are also involved in chemotaxis. Another key action of activated eosinophils is the release of reactive oxygen species, causing tissue damage during chronic inflammatory responses. Blocking eosinophil activation and the signaling pathways that lead to chemotaxis, degranulation, and reactive oxygen release may alleviate inflammatory conditions and inflammation-associated tissue damage. (This definition may be outdated - see the DesignNote.)
The chemokine receptors CCR5 and CXCR4 in macrophages are activated by their peptide ligands and also by the HIV envelope protein GP120 during HIV infection. One mechanism of signaling by these GPCRs is through activation of Gi signaling. These chemokine receptors can also signal through a Gi-independent pertussis toxin-insensitive pathway. This pathway elevates calcium influx into the cell through CRAC channels, ion channels that are activated by calcium release. Elevated calcium from CRAC is required for downstream activation of Pyk2, a focal adhesion-associated protein kinase. Non Gi signaling by these chemokine receptors also involves the Jnk and p38 Map kinase pathways leading to AP-1 activation and activation of genes such as MIP-1 and MCP-1. This pathway may be involved in the role of macrophages in the pathogenesis of AIDS. (This definition may be outdated - see the DesignNote.)
An immunotoxin composed of an anti-CD22 monoclonal antibody and a toxin moiety, which targets antigen-positive cells and causes cytotoxic activity. (NCI)
A finding that a sample of neoplastic cells has detectable immunoreactivity for CD30 (TNFRSF8).
An immunotoxin composed of an anti-CD30 monoclonal antibody and a toxin moiety, which targets antigen-positive cells and causes cytotoxic activity. (NCI)
The CD40 receptor was first associated with expression in B cells and the role it plays through its ligand CD40L (CD154) in moderating T cell activation. Broader expression may indicate a broader role for CD40 and CD40L in immune function and disease states such as transplant rejection and HIV infection. Disruption and modulation of CD40 interaction with CD40L may prove therapeutic in the treatment of autoimmune disorders, heart disease, and cancer. As a member of the TNF receptor family, CD40 relies on interaction with TRAF proteins to mediate an intracellular signal in response to CD40L binding. The pathway downstream of TRAFs activates the transcription factor NF-kappaB through a kinase pathway involving map kinases, NIK (NF-kappaB inducing kinase) and I-kappa B kinases. Some CD40 responses like regulation of immunoglobulin expression might be mediated by NF-kappaB transcriptional activation. (This definition may be outdated - see the DesignNote.)
Cdc25 is a protein phosphatase responsible for dephosphorylating and activating cdc2, a crucial step in regulating the entry of all eukaryotic cells into the M-phase of the cell cycle. Cdc25 is phosphorylated throughout interphase but not in mitosis. The primary site for phosphorylation of cdc25 is Ser216. Phosphorylated cdc25 binds to members of the 14-3-3 family of proteins which prevents its activation of cdc2. Chk1, a protein kinase involved in the DNA damage checkpoint response in fission yeast, has been shown to phosphorylate cdc25 at Ser216 in vitro. (This definition may be outdated - see the DesignNote.)
A mutation in the CDKN2A gene that either inhibits expression of the CDKN2A protein or results in the translation of an inactive CDKN2A protein.
Initiation of DNA replication in eukaryotes is a highly conserved, multi-step process (replication licensing) designed to restrict initiation events to once per replication origin per S phase. Its control has been uncovered by the discovery of the cyclin dependent kinases (CDKs) as master regulators of the cell cycle and the initiator proteins of DNA replication, such as the Origin Recognition Complex (ORC), Cdc6/18, Cdt1 and the mini-chromosome maintenance complex (Mcm). The proteins and the sequence of events involved in this process are conserved throughout the eukaryotic kingdom. First, the ORC comprised of six proteins binds to replication origins in the chromosomal DNA. At the end of mitosis, ORC, Cdc6/18 and Cdt1 assist the binding of Mcm proteins 2-7 to chromatin, and chromatin becomes licensed for replication. The activated Mcm complex functions as a replicating helicase and moves along with the replication fork to bring the origins to the unlicensed state. The cycling of CDK activity in the cell cycle regulates the two states of replication origins, the licensed state in G1-phase and the unlicensed state for the rest of the cell cycle. The restriction on licensing is relieved when CDK falls off at the completion of mitosis to allow a new round of replication. (This definition may be outdated - see the DesignNote.)
The defects in cAMP-regulated chloride channel CTFR are believed to be the major cause for cystic fibrosis. Regulation of CFTR protein by the surface receptor beta adrenergic receptor is mediated through the ezrin/radixin/moesin binding phosphoprotein 50 (EBP50), which binds both the C-termini CFTR and b2AR through their PDZ binding motifs. In the resting state, CFTR, b2AR, and EBP50 exist as a macromolecular complex on the apical surface of epithelial cells. Upon agonist activation of the b2AR, the adenylate cyclase is stimulated through the G protein pathway, leading to an increase in cAMP. The elevated concentration of cAMP activates PKA, which is anchored near CFTR via interaction with Ezrin. The phosphorylation of CFTR by PKA disrupts the complex and leads to compartmentalized and specific signaling of the channel. (This definition may be outdated - see the DesignNote.)
A recombinant peptide fragment containing adhesion domains of fibronectin. Fibronectin is high molecular weight glycoprotein, and has important roles in cell adhesion, morphology, and surface architecture. Fibronectin fragment CH-296 is used in retroviral-based gene transfer procedures, which utilizes adhesive property of fibronectin to bring virions to target cells and to facilitate co-localization, thereby increasing gene transfer efficiency.
A change in the nucleotide sequence of the CHEK2 gene.
Cdk5 is a cyclin dependent protein kinase involved in dopaminergic signaling in the neostriatal region of the brain. The role of cdk5 in dopamine responses occurs through phosphorylation of DARPP-32. Casein kinase 1 (CK1) also regulates DARPP-32 phosphorylation and dopamine signaling. The phosphorylation of DARPP-32 by cdk5 reduced dopamine signaling. Depending on its phosphorylation state, DARPP-32 inhibits either protein phosphatase 1 (PP1) or PKA. The role of mGLUR1 in this process is supported by the induction of cdk5 and CK1 activity by the mGLUR1 agonist DHPG and the subsequent phosphorylation of DARPP-32 associated with DHPG treatment of nigrostriatal neurons. CK-1 and Ckd5 inhibitors block the DHPG induced DARPP-32 phosphorylation. Dopamine exerts a positive signal that increases dopamine response by reversing phosphorylation of DARPP-32 at threonine-75. Dopamine initiates this pathway through activation of the D1 dopamine receptor, a Gs coupled GPCR, elevating cAMP and activating PKA. PKA activates protein phosphatase 2A (PP2A) which dephosphorylates DARPP-32 and increases dopamine responsiveness. This also removes the inhibition of PKA by DARPP-32, forming a positive feedback loop for further DARPP-32 inactivation by PKA. Activation of the D2 dopamine receptor has the opposite effect, shifting the DARPP-32 population toward the threonine-75 phosphorylated form. (This definition may be outdated - see the DesignNote.)
The transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including neurotransmitters, hormones, membrane depolarization, and growth and neurotrophic factors. Protein kinase A and the calmodulin-dependent protein kinases CaMKII stimulate CREB phosphorylation at Ser133, a key regulatory site controlling transcriptional activity. Growth and neurotrophic factors also stimulate CREB phosphorylation at Ser133. Phosphorylation occurs at Ser133 via p44/42 MAP Kinase and p90RSK and also via p38 MAP Kinase and MSK1. CREB mutants exhibit deficiencies in spatial learning tasks, while flies overexpressing or lacking CREB show enhanced or diminished learning, respectively. (This definition may be outdated - see the DesignNote.)
Interaction of T cell receptor with specific antigen in the context of MHC II activates a signal transduction pathway that leads to T cell activation. In the T cell receptor signaling pathway, the src family kinases Lck and Fyn are activated to phosphorylate proteins in the T cell receptor complex which recruit and activate the ZAP70 kinase. The activation of ZAP70 phosphorylates downstream targets that activate MAP kinase pathways and cause T cell activation. The CD45 phosphorylase also plays a role in T cell receptor signaling, dephosphorylated Lck and Fyn to activate them. Other factors modulate T cell receptor activation. Csk (COOH-terminal Src kinase) phosphorylates Lck and deactivates it, opposing the action of CD45. The phosphorylation of Lck by Csk inhibits T cell receptor signaling and inhibits T cell activation. Csk activity is regulated in T cells by PKA, the cAMP-dependent protein kinase activated by the second messenger cAMP. The activity of Csk also appears to depend on other factors such as CBP, which recruits Csk to the plasma membrane in lipid rafts where other signaling factors such the T cell receptor complex are localized. CBP also directly activates Csk. (This definition may be outdated - see the DesignNote.)
CTCF is central to signaling pathways in immature B cells elicited by cross-linking the Ig BCR and stimulation with TGF. Both stimuli result in induction of cell cycle arrest and apoptosis. BCR ligation stimulates a transient induction of MYC that leads to high level CTCF expression and feedback suppression of MYC transcription. BCR ligation also activates PTEN opposing PI3K activation of MYC. Pharmacologic inactivation of PI3K or mTOR/FRAP results in suppression of S6K resulting in activation of CTCF and suppression of MYC. CTCF activation induces transcriptional activation of p19ARF, with its downstream consequences, and of p27. Growth arrest is occasioned by co-expression of p21 and p27 and inhibition of MYC. CTCF, is a multivalent DNA-sequence binder whose specificity is mediated by different sets of zinc finger (ZF) proteins. (This definition may be outdated - see the DesignNote.)
Cytotoxic T lymphocytes (CTLs), also known as killer T cells, provide a cell-mediated response to specific foreign antigens associated with cells. CTLs only respond to foreign antigen when it is presented bound to the MHC-1 expressed on the surface of cells. CTLs do not respond to soluble antigen, but induce apoptosis in viral-infected cells and in cancer cells. When the complex of antigen bound to MHC-1 is bound to antigen-specific T cell receptor, the cytotoxic T cell induces apoptosis in the target cell primarily by two pathways, one involving perforin-mediated apoptosis and the other involving Fas/Fas-ligand interaction. When CTLs are activated by recognition of specific antigen on a cell, they release perforin proteins that integrate into the membrane of the target cell and organize to form a membrane pore. This allows the protease granzyme to enter the cell and activate the apoptotic caspase proteolytic cascade, and also allows other molecules to cross the cell membrane and trigger osmotic lysis of the membrane. The interaction of T-cell Fas ligand with the Fas receptor in the target cell can also activate the caspase cascade and other pathways involved in apoptosis. The interaction of a CTL with antigen-MHC I complex activates the CTL to proliferate and amplify the clone of T cells that respond to that antigen, amplifying the immune response against that specific antigen. (This definition may be outdated - see the DesignNote.)
A series of molecular signals initiated by a the C-X-C chemokine type 4 receptor on the surface of a cell binding to one of it's physiological ligands, and ending with regulation of a downstream cellular process, e.g. transcription. [GOC:nhn, GOC:signaling]
A cancer vaccine consisting of a peptide derived from MAGE-3 and the pan-DR epitope (PADRE), an immunostimulant. Vaccination with CY-2010 may elicit a cytotoxic T lymphocyte (CTL) immune response against tumor cells expressing MAGE-3. MAGE-is an antigen found on many tumor cell types, including melanoma and lung, prostate, colon, thyroid, and breast cancers. (NCI04)
Mutation of the CEBPA gene encoding CCAAT/enhancer binding protein alpha. It is seen in acute myeloid leukemias usually associated with a normal karyotype.
Exposure to divalent cadmium ions (Cd2+) is a known cancer risk factor, but the molecular mechanisms responsible for the inappropriate induction of cellular proliferation by cadmium are still being figured out. One cellular model used to study this process is macrophages grown in culture. In cultured macrophages, cadmium acts both at the cell surface and in the cytoplasm to induce proliferation. At the cell surface, cadmium interacts with a pertussis-sensitive cell surface receptor, probably a Gi-coupled GPCR, to stimulate proliferation. Cadmium can enter cells through calcium ion channels and once in cells affects calcium release by the ER. In addition to changes in intracellular calcium, the proliferative effects of cadmium are mediated by the Ras/Map kinase pathway, and also NF-kB. Inhibition of phospholipase C, map kinases, or NF-kB with a variety of pharmacological inhibitors all blocked the activation of cellular proliferation by cadmium. Protein kinase C is also activated by cadmium, upstream of the Map kinase pathway. Changes in transcription induced by cadmium include induction of immediate early genes like fos, jun, and myc. In addition to inducing cellular proliferation, cadmium also is slightly genotoxic due to inhibition of DNA repair, activates stress genes, and inhibits the immune system. The immunomodulatory effects observed with cadmium treatment may also involvement transcriptional disregulation, including the expression of cytokines such as IL-4, IL-10, and TNF-alpha. Although macrophages have been used for many studies, other cell types are also the target of cadmium's toxicity. (This definition may be outdated - see the DesignNote.)
A term that usually refers to the clinical course of lymphomas and indicates that the cancerous lymph nodes are next to each other.
Copper Chelation involves non-covalent coordination bonding between copper and an organic chemical, often as part of an enzyme.
Synthetic compounds or mixtures that usually contain a combination of any of the following agents depending on the symptoms that need to be treated: an antitussive, a decongestant, an antihistamine, an analgesic antipyretic, an expectorant and/or an anticholinergic agent. A cough and cold preparation is usually administered orally to relieve symptoms of the cold, flu or allergy, such as cough, congestion, itchy, watery eyes, runny nose, sore throat and fever.
A physical connection between two atoms or radicals in which a chemical bond is formed by sharing electrons.
A B-cell non-Hodgkin lymphoma arising from the skin. Representative examples include cutaneous marginal zone B-cell lymphoma and cutaneous follicle center lymphoma.
A bacterial cell wall mimetic. It is a potent inducer of cytokines and is beginning Phase II trials in combination with chemotherapy for patients with non-small cell lung cancer.
The chemical reactions and pathways involving cyanoamino acids, amino acid derivatives that contain a cyanide group. [GOC:mah, PMID:11575729]
Any substance that inhibits cyclin-dependent kinase (CDK), an enzyme that catalyzes the addition of a phosphate group to a protein in the cell cycle regulation pathway. Inhibition of cyclin-dependent kinase results in cell cycle arrest and apoptosis.
A molecular abnormality indicating the presence of an abnormally high level of the G1/S-specific cyclin-D1 protein.
Cyclins are proteins that associate with cyclin-dependent protein kinases to regulate their activity and the progression of the cell cycle through specific checkpoints. The cyclical increase and decrease in cyclin levels is a key to cell cycle regulation. Disruption of cyclin action can lead to either cell cycle arrest, or to uncontrolled cell proliferation. When cyclin E is abundant it interacts with the cell cycle checkpoint kinase cdk2 to activate cdk2 and allow progression of the cell cycle from G1 to S phase. One of the key targets of activated cdk2 complexed with cyclin E is the tumor suppressor Rb. When dephosphorylated in G1, Rb complexes with and blocks transcriptional activation by E2F transcription factors. When Rb is phosphorylated by cdk2/Cyclin E, it dissociates from E2f, allowing E2F to activate the transcription of genes required for S phase. One of the genes activated by E2F is cyclin E itself, leading to a positive feedback cycle as cyclin E accumulates. The decision by the cell to either remain in G1 or progress into S phase is the result in part of the balance between cyclin E production and proteolytic degradation in the proteasome. Cyclin E is targeted for destruction by the proteasome through ubiquitination when associated with a complex of proteins called the SCF or F box complex. Proteins included this complex include an F box protein that targets specific substrates such as Cyclin E for degradation. In the case of cyclin E the F box protein Fbw7, also called hCdc4, associates with phosphorylated free cyclin E to recruit it into the SCF complex for degradation. SCFFbw7 is a ubiquitin ligase recruited into the complex that specifically targets cyclin E. Cul3, skp1, and Rbx1 also are part of the complex that degrades cyclin E. There may be redundancy for some components of the complex since cul1 deletion also disrupts cyclin E degradation, and multiple F box proteins may contribute to cyclin E degradation. The interaction of multiple different factors in cyclin E accumulation integrates different signaling pathways with cell cycle regulation and may play a role in the unregulated cell cycle progression of cancer. (This definition may be outdated - see the DesignNote.)
The cell cycle is regulated by the interplay of many molecules. Key among these are the cyclins which are expressed and then degraded in a concerted fashion to drive the stages of the cell cycle. Cyclins combine with cyclin dependent kinases (cdks) to form activated kinases that phosphorylate targets leading to cell cycle regulation. A breakdown in the regulation of this cycle can lead to out of control growth and contribute to tumor formation. Defects in many of the molecules that regulate the cell cycle have been implicated in cancer. Key among these are p53, the cdk inhibitors (p15, p16, p18, p19, p21, p27), and Rb, all of which act to keep the cell cycle from progressing until all repairs to damaged DNA have been completed. (This definition may be outdated - see the DesignNote.)
Cyclooxygenase Interaction involves temporary non-covalent binding, typically through intermolecular physical forces of attraction and spatial complementarity, between a molecular entity and Cyclooxygenase, an enzyme complex that catalyzes the formation of prostaglandins from unsaturated fatty acid, molecular oxygen, and a reduced acceptor.
A microscopic finding indicating the formation of cystic structures in a tissue sample.
A pathologic process that contains a single or multiple sac-like spaces.
Any substance that inhibits cytidine deaminase, an enzyme that scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis. Inhibition of cytidine deaminase increases the biological half-life of cytidine-containing compounds.
Any substance that inhibits cytidine triphosphate synthetase, an enzyme that catalyses the rate-limiting step in the synthesis of CTP. Inhibition of cytidine triphosphate synthetase interferes with DNA, RNA, and CTP biosynthesis and can cause cell cycle arrest.
Several different cell types coordinate their efforts as part of the immune system, including B cells, T cells, macrophages, neutrophils, basophils and eosinophils. Each of these cell types has a distinct role in the immune system, and each communicates with other immune cells using secreted factors called cytokines, including interleukins, TNF, and the interferons. Macrophages phagocytose foreign bodies and are antigen-presenting cells, using cytokines to stimulate specific antigen dependent responses by B and T cells and non-specific responses by other cell types. T cells secrete a variety of factors to coordinate and stimulate immune responses to specific antigen, such as the role of helper T cells in B cell activation in response to antigen. The proliferation and activation of eosinophils, neutrophils and basophils respond to cytokines as well. Cytokine communication is often local, within a tissue or between cells in close proximity. Each of the cytokines is secreted by one set of cells and provokes a response in another target set of cells, often including the cell that secretes the cytokine. Some cytokines, like IL-1, interferons and TNF, stimulate a broad inflammatory response in response to infection or injury. Other cytokines have more specific functions such the following examples. IL-2 stimulates the proliferation and activation of B and T cells. IL-4 plays a role in the differentiation of Th2 cells, in allergic responses, and in the switching of antibody types. IL-5 stimulates the production and maturation of eosinophils during inflammation. IL-8 is a chemokine, a chemotactic factor that attracts neutrophils, basophils and T cells to sites of inflammation. IL-12 and IL-18 are involved in helper T cell differentiation. IL-10 apparently acts to repress secretion of proinflammatory cytokines. The complex interplay of these different cytokine functions with immune cells is essential for correct immune function. (This definition may be outdated - see the DesignNote.)
A process that involves the binding of any member of the cytokine family to a cognate cytokine receptor. These interactions are involved in the regulation of responses that promote antibody synthesis and cellular immune functions.
Any environment-to-cell cummunication that involves cytokines. This process is involved in immune function.
D4-GDP dissociation inhibitor (D4-GDI) is a negative regulator of the ras related Rho Family of GTPases. Since the rho GTPases promote cytoskeletal and membrane changes associated with apoptotic cell death, the removal of the D4-GDI block through its cleavage is important for inducing apoptosis. Caspase-3 cleaves the 28 kDa mature form of D4-GDI to give a 5 kDa and 23 kDa size fragment. The 23 kDa fragment then translocates to the nucleus. The mechanisms involving cleavage of D4-GDI with apoptosis are not presently known. Activation of the Jun N-Terminal kinase, a regulator of apoptosis, may be one of the mechanisms. (This definition may be outdated - see the DesignNote.)
Endothelial cells respond to treatment with the protease thrombin with increased secretion of the PDGF B-chain. This activation occurs at the transcriptional level and a thrombin response element was identified in the promoter of the PDGF B-chain gene. A transcription factor called the DNA-binding protein B (dbpB) mediates the activation of PDGF B-chain transcription in response to thrombin treatment. DbpB is a member of the Y box family of transcription factors and binds to both RNA and DNA. In the absence of thrombin, endothelial cells contain a 50 kD form of dbpB that binds RNA in the cytoplasm and may play a role as a chaperone for mRNA. The 50 kD version of dbpB also binds DNA to regulate genes containing Y box elements in their promoters. Thrombin activation results in the cleavage of dbpB to a 30 kD form. The proteolytic cleavage releases dbpB from RNA in the nucleus, allowing it to enter the nucleus and binds to a regulatory element distinct from the site recognized by the full length 50 kD dbpB. The genes activated by cleaved dbpB include the PDGF B chain. Dephosphorylation of dbpB also regulates nuclear entry and transcriptional activation. RNA digestion in vitro can release dbpB in its active form, suggesting that the protease responsible for dbpB may be closely associated in a complex. Identification of the protease that cleaves dbpB, the mechanisms of phosphorylation and dephosphorylation, and elucidation of the signaling path by which thrombin induces dbpB will provide greater understanding of this novel signaling pathway. (This definition may be outdated - see the DesignNote.)
An agent capable of attaching to DNA with a covent bond. DNA adduct forming agents cause disruption of DNA replication and mitosis.
DNA Adduction involves formation of a covalent bond between a molecule and the DNA macromolecule.
DNA binding molecules regulate mechanisms central to cellular function, including DNA replication and gene expression. Many small molecules that mimic or block these processes offer potential therapeutic agents. Understanding how complexation affects both the structural and mechanical properties of DNA is an important step towards understanding the functional mechanisms of binding agents, and may also provide a key to more rational drug design. There are three major classes of binding modes: intercalation, groove binding and covalent crosslinking.
A synthetic peptide used to formulate and deliver deoxyribonucleic acids (DNA, usually in plasmid form) in gene therapy. The carrier peptides may condense plasmids into nano-particles with a hydrodynamic diameter ranging from 40 to 200 nm, which are sterically stable for long periods of time. Peptide-based gene delivery systems are used for transfection in a variety of cell lines. (NCI04)
DNA Crosslinking involves the formation of a covalent bond between two bases on DNA. (NCI)
A DNA Double Strand Break involves a disruption of the covalent linkages among the phosphodeoxyribose moieties within the sugar-phosphate backbone in both strands of a DNA molecule.
Energetics and biophysical mechanisms of DNA higher order structure
An agent that binds covalently or non-covalently in the major or minor groove of DNA and can disrupt DNA replication.
DNA Interstrand Crosslinking involves the formation of a covalent bond between two bases on different DNA strand. (NCI)
DNA Intrastrand Crosslinking involves the formation of a covalent bond between two bases on the same DNA strand. (NCI)
An agent that binds to the major groove of DNA, interfering with DNA replication.
DNA Methylation Inhibition involves interference with, or restraint of, the process by which methyl groups are added to genomic DNA nucleotides.
DNA Methylation Regulation involves cellular mechanisms that control covalent addition of methyl groups to specific cytosine residues of a DNA molecule, which typically influence gene expression and other genetic functions.
An antineoplastic agent that either covalently or noncovalently binds to the minor groove of DNA, causing inhibition of DNA synthesis. (NCI)
A topical agent containing a DNA repair enzyme.
DNA sequence errors introduced via DNA replication.
A DNA Single Strand Break involves one or more disruptions of the covalent linkages among phosphodeoxyribose moieties within the sugar-phosphate backbone in one strand of a DNA molecule.
Apoptosis is specifically induced via signaling through a family of receptors known collectively as 'death receptors' including Fas, TNFR, DR3, -4 and -5. Death receptor ligands characteristically initiate signaling via receptor oligomerization, recruitment of specialized adaptor proteins and activation of caspase cascades. Apo3L recruits initiator caspase 8 via the adapter protein FADD. Caspase 8 then oligomerizes and is activated via autocatalysis. Activated caspase 8 stimulates apoptosis via two parallel cascades: it directly cleaves and activates caspase-3, and it cleaves Bid (a Bcl-2 family protein). Truncated Bid (tBid) translocates to mitochondria, inducing cytochrome C release, which sequentially activates caspases 9 and 3. DR-3L can deliver pro- or anti-apoptotic signals. DR-3 promotes apoptosis via the adaptor proteins TRADD/FADD and the activation of caspase 8. Alternatively, apoptosis is inhibited via an adaptor protein complex including RIP which activates NF-kB and induces survival genes including IAP. Induction of apoptosis via Apo2L requires caspase activity, but the adaptor requirement is unclear. (This definition may be outdated - see the DesignNote.)
Deacetylation is the covalent chemical or post-translational biochemical removal of an acetyl group(s) from organic compounds.
Refers to a mechanism leading to a fixed state of immunity that fails to adapt to a changing pathogen and has lost the ability to discriminate antigen after the establishment of a strong primary immune response.
The hydrochloride salt form of deferoxamine, an iron chelating agent. Deferoxamine chelates iron from intra-lysosomal ferritin and hemosiderin forming ferrioxamine, a water-soluble chelate excreted by the kidneys and in the feces via the bile. This agent does not readily bind iron from transferrin, hemoglobin, myoglobin or cytochrome. (NCI)
Definite adverse event attribution to study product or procedure is established when there is a clear-cut temporal association between product or procedure administration and adverse event, and no other possible cause is present.
A nitrogen mustard compound that cross-links with DNA, causing inhibition of DNA synthesis. (NCI)
Any rearrangement to the genomic content that results in the loss of one or more nucleotides of DNA. Deletions are generally irreversible rearrangements. They may alter the reading frame of a gene, or may result in loss of large chromosomal regions.
A vaccine composed of dendritic cells pulsed with tumor cells lysates that stimulate a potent and specific cell mediated anti-tumor immune response. (NCI)
A vaccine composed of dendritic cells pulsed with peptide epitopes that stimulate cytotoxic T lymphocyte anti-tumor activity. (NCI)
A vaccine made of antigens and dendritic antigen-presenting cells (APCs).
A folate analog that interferes with RNA, DNA, and protein synthesis. (NCI)
This term refers to the growth of fibrous or connective tissue. Some tumors elicit a desmoplastic reaction, the pervasive growth of dense fibrous tissue around the tumor. Scar tissue (adhesion) within the abdomen after abdominal surgery is another type of desmoplastic reaction. (MedicineNet.com)
An anticancer drug that is a type of angiogenesis inhibitor.
A characteristic of an organism that contributes to the diagnosis or treatment of a disease or to the prediction of clinical outcomes.
A sulfonylurea compound containing aryl groups with potential antineoplastic activity. Originally developed as herbicides, diarylsulfonylureas have shown a broad spectrum of antitumor activity in vivo. The precise mechanism of antitumor action has not yet been elucidated, however, certain diarylsulfonylurea compounds have been shown in preliminary studies to exert antimitotic effects through their inhibition of tubulin polymerization, and others have been shown to be effective antitumor agents in animal models by the mechanism of uncoupling mitochondrial oxidative phosphorylation.
The degradation of endogenous mRNA in a sequence-specific manner can be induced by dsRNA [RNA interference (RNAi)], antisense transcription, or viral infection. In the current model for posttranscriptional gene silencing by RNAi, the ribonuclease III like enzyme Dicer processes dsRNA into small fragments (siRNA) of 21-25 nts. The siRNA is incorporated into the RNA-induced silencing complex (RISC), which targets and degrades the homologous mRNA. Most of the proteins in the RISC (with the exception of Ago2 and Dicer have not been identified) but likely contain endonuclease, helicase, exonuclease and homology scanning activity. (This definition may be outdated - see the DesignNote.)
An antimetabolite and folate analogue with anti-proliferative activity. Dideazatetrahydrofolic acid inhibits activity of glycinamide ribonucleotide formyltransferase (GARFT), the first folate-dependent enzyme of the de novo purine synthesis pathway essential for cell proliferation. Enzyme inhibition reduces the purine nucleotides pool required for DNA replication and RNA transcription. As a result, this agent causes cell cycle arrest in S-phase, and ultimately inhibits tumor cell proliferation.
A neuroblastoma in which the differentiating neuroblasts constitute more than five-percent of the tumor cells.
An agent that inhibits the differentiation or maturation of cells, specifically neoplastic cells.
A syndrome characterized by multiple, benign nodular smooth muscle neoplasms of the esophagus, tracheobronchial tree and the genitourinary tract. Clinical signs include dysphagia with retrosternal pain, dyspnea and genital hypertrophy. There is a strong association with Alport Syndrome in patients with deletions in the type IV collagen alpha chain genes COL4A5 and COL4A6.
Any substance that inhibits dihydroorotate reductase, an enzyme required for de novo biosynthesis of pyrimidine. Inhibition of dihydroorotate reductase interferes with DNA and RNA synthesis.
Any substance that inhibits dihydropyrimidine dehydrogenase, a rate limiting enzyme in the degradation of pyrimidines. Inhibition of dihydropyrimidine dehydrogenase increases the biological half-life and efficacy of 5-Fluorouracil (5-FU).
A substance originally isolated from the marine mollusk Dolabella auricularia with potential neoplastic activity. Dolastatin 9 binds to tubulin and blocks microtubule assembly, thereby inhibiting mitosis. (NCI04)
Any of a class of natural peptides originally isolated from the marine mollusk Dolabella auricularia that bind to tubulin at the vinca/peptide region, thereby inhibiting microtubule assembly and leading to cell cycle arrest and/or apoptosis.
A aluminum solution with astringent, antibacterial, and antifungal properties. Domeboro solution is a commercial preparation of modified Burow's solution, (5% aluminum acetate) by Bayer. Aluminum sulfate, the active ingredient of Domeboro, is attributed for this agent's bacteriostatic effect. Domeboro is used most often to cleanse irritated skin and soothe inflammation.
Any mutation that encodes an altered gene product that acts to antagonize the wild-type allele. Dominant negative mutations are characterized by a dominant or semi-dominant phenotype, and usually result in loss of function.
The sodium salt of Dorzolamide. An inhibitor of carbonic anhydrase, a zinc-containing enzyme that catalyzes the rapid conversion of carbon dioxide and water into carbonic acid, protons and bicarbonate ions. Distributed throughout many cells and tissues, various carbonic anhydrases play important roles in mineral and metabolic homeostasis. (NCI04)
Transport of drugs out of a cell. A mechanism of drug resistance.
A finding indicating a deficiency or excess in metabolism of one or more drugs.
Drug Metabolism Induction involves the initiation of enzymatic biotransforming chemical modifications exerted on a naturally occurring or synthetically produced organic or inorganic substances, elements, and isotopes used in research or for prevention, diagnosis, and /or treatment of disease states.
Drug Metabolism Inhibition involves interference with, or restraint of, enzymatic biotransforming chemical modifications exerted on a naturally occurring or synthetically produced organic or inorganic substances, elements, and isotopes used in research or for prevention, diagnosis, and /or treatment of disease states.
Any drug derived from microorganisms, plants, or animals; also, synthesized versions of these substances or their derivatives.
A spirocyclopropylhexadienone-containing antineoplastic antibiotic isolated from Streptomyces bacterial species or derived synthetically. Duocarmycin antibiotics alkylate DNA by binding to adenine-thymine (A-T)- rich sequences in the minor groove of DNA, thereby inhibiting DNA replication and inducing apoptosis.
Expression of a fusion protein that results from a t(1;19)(q23;p13) translocation, which involves the human genes E2A and PBX1 and is associated with B lymphoblastic leukemias.
E2F-1 is a transcription factor that regulates the expression of genes involved in the cell cycle and that is involved in progression of the cell cycle from G1 into S phase. Over-expression of E2F-1 can induce cellular transformation and under-expression can repress apoptosis. Association with the tumor suppressor Rb represses E2F-1 activity, and this repression is relieved when the cdk2/cyclin E complex at the G1 to S phase transition phosphorylates Rb. Like many cell cycle regulators, E2F-1 is regulated through phosphorylation by a cyclin-dependent protein kinase, cdk2/cyclin A, and by proteolytic degradation. Phosphorylation of E2F-1 by cdk2/cyclin A leads to E2F-1 inactivation, blocking DNA binding. E2F-1 is also regulated through degradation in the proteasome at the S/G2 transition. The F box complex that degrades E2F-1 contains components shared with the complexes that target other cell cycle factors for degradation. The F box protein that specifically recruits E2F for ubiquitination and degradation is Skp2. Other components of the SCF complex include Skp1, Cul1, and cdc34. Skp2 expression is cyclical, increasing in the S/G2 transition as E2F-1 is degraded. Knowledge of E2F-1 activity and its regulation form part of the complex set of interactions regulating the cell cycle and potential targets for the treatment of cancer. (This definition may be outdated - see the DesignNote.)
A molecular genetic abnormality indicating the presence of multiple copies of the EGFR gene.
A molecular genetic abnormality indicating the presence of an abnormally high level of EGFR protein.
A synthetic peptide sequence derived from the tumor specific mutant variant of epidermal growth factor receptor EGFRvIII originally found in glioblastoma multiforme, caused by the deletion of exons 2-7. Unlike wild-type EGFR, EGFRvIII is a dominant oncogene that can directly lead to cancer. EGFRvIII is expressed in multiple cancer types including breast, ovarian, and metastatic prostate cancers, and other types of solid tumors due to alternative splicing; has not been observed in normal human tissues. Vaccination with EGFRvIII peptide may stimulate the host immune system to mount a cytotoxic T lymphocyte response against tumor cells positive for EGFRvIII, resulting in decreased tumor growth. (NCI04)
As with many cell-surface receptors, activation of the EGF receptor can result in receptor internalization through receptor-mediated endocytosis, desensitizing further receptor signaling. This process requires clathrin and occurs in clathrin-coated pits, which pinch off from the plasma membrane to form vesicles that move to the early endosome. From the early endosome, receptors can either be recycled back to the cell surface, or they can move through the late endosome to the lysosome for proteolytic degradation. The sorting of receptors in the early endosome for degradation requires the tyrosine kinase activity of activated growth factor receptor and involves ubiquitination of the receptor. Targeting of receptors for degradation requires members of the Cbl gene family. Cbl proteins bind to tyrosine phosphorylated EGF receptor, and are E3 ubiquitination ligases that label receptor for degradation. Cbl also recruits Cin85 to the receptor complex, and blocking Cin85 interaction blocks receptor internalization and degradation. Endophilins are also a member of this receptor-bound protein complex. In its role as a ubiquitin ligase and docking protein, Cbl desensitizes EGF signaling and also opposes cellular proliferation induced by EGF. EGF activation also appears to activate the tyrosine kinase Src, which phosphorylates Cbl, and helps to activate the ubiquitination and degradation of EGF receptor. PKC activation and threonine phosphorylation of the EGF receptor can induce heterologous receptor internalization, but opposes Cbl-mediated receptor degradation. PKC phosphorylated receptors are sorted for recycling to the cell surface, and directed away from the late endosome and proteasome. Other growth factor receptors are regulated in a similar manner, including the PDGF receptor, HGF receptor and the CSF-1 receptor, indicating that this is a fairly general regulatory mechanism. The importance of Cbl in the down-regulation of growth factor signaling means that it will have an important role in cellular transformation and the development and treatment of cancer. (This definition may be outdated - see the DesignNote.)
The epidermal growth factor (EGF) peptide induces cellular proliferation through the EGF receptor. Inhibitors of the EGF receptor are being pursued as potential cancer therapies and EGF may stimulate wound healing. Mutation of the EGF receptor has been associated with cancer in humans. The proliferative effects of EGF are signaled through several pathways. Binding of EGF results in EGF receptor dimerization, autophosphorylation of the receptor, and tyrosine phosphorylation of other proteins. The EGF receptor activates ras and the MAP kinase pathway, ultimately causing phosphorylation of transcription factors such as c-Fos to create AP-1 and ELK-1 that contribute to proliferation. Activation of STAT-1 and STAT-3 transcription factors by JAK kinases in response to EGF contributes to proliferative signaling. Phosphatidylinositol signaling and calcium release induced by EGF activate protein kinase C, another component of EGF signaling. Crosstalk of EGF signaling with other pathways make the EGF receptor a junction point between signaling systems. (This definition may be outdated - see the DesignNote.)
An electrocardiographic finding about the position of the heart in the chest (axis). The electrical axis of the heart is a term used to describe the mean direction and magnitude of electrical impulses generated by the heart during the cardiac cycle. Normally, the heart is positioned in the chest so that the majority of the electrical impulse travels downward (interior) and towards the left. The normal axis of the heart is called normal axis deviation. Age, body build, and sex may influence axis location and produce a number of normal variations. The axis may deviate from normal position due to structural problems (valve conditions), pulmonary or systemic hypertension and/or heart attacks.
A murine monoclonal antibody targeting the epidermal growth factor receptor (EGFR) exhibiting anti-tumor activity. EMD 55900 antibody binds to the extracellular domain of EGFR close to the EGF binding domain and does not induce any tyrosine kinase activity on its own. As a result, EMD 55900 binding inhibits receptor activation by natural ligands thereby interrupting activation of downstream signaling cascade, required for tumor cell growth and proliferation.
Erythropoietin functions to increase the number of red blood cells. Thus, it has found utility as a drug for those needing to replenish erythrocytes for any number of reasons. The signaling mechanism includes multimerization of the receptor upon ligand binding, activation of MAPK cascade, and phosphorylation and activation of Stat5. (This definition may be outdated - see the DesignNote.)
A molecular genetic abnormality indicating the presence of multiple copies of the ERBB2 gene.
A series of molecular signals initiated by binding of a ligand to a member of the ERBB family of receptors on the surface of a cell, where the signal is transmitted by ERBB2. The pathway ends with regulation of a downstream cellular process, e.g. transcription. ERBB2 receptors are themselves unable to bind to ligands, but act as a signal-amplifying tyrosine kinase within a heterodimeric pair. [GOC:jc, PMID:16460914, PR:000002082, Reactome:REACT_115755.1]
The endoplasmic reticulum (ER) of the cell operates a quality control system that identifies misfolded proteins, transports them into the cytoplasm and then targets them for degradation by the proteasome. Aberrant protein degradation is the mechanism underlying many diseases, including cystic fibrosis and heritable forms of lung and liver disease. The pathways that orchestrate the destruction of aberrant proteins are collectively termed ER-associated degradation (ERAD). Most of the proteins synthesized in the ER are cotranslationally modified with N (asparagine)-linked glycans by addition of triglycosylated, branched oligosaccharides at asparagines residues. Rapid glucose trimming by ER glucosidases generates monoglucosylated N-glycans (Glc0-3Man9GlcNAc2). Productive folding of the polypeptides to which the glycans are attached requires the services of an ER lectin chaperone called calnexin (CNX) that recognize the Glc1Man9GlcNAc2 oligosaccharide and assists the folding of newly synthesized glycoproteins. Because the half-time of monoglucose in the nascent glycoproteins is about 2 min, the protein should be repeatedly reglycosylated by UDP-glucose: glycoprotein glucosyltransferase (UGGT) resulting in association with CNX. Next, the mannose residue from the middle branch of the Man9GlcNAc2 oligosaccharide is removed by ER -mannosidase I, then correctly folded glycoproteins bearing Man8GlcNAc2 isomer B (Man8B form) are transported out of the ER to the Golgi apparatus. If the native structure of the glycoprotein cannot be achieved it is retained in the ER. When substrates are released from CNX by glucosidase II, they may be transferred to one of 2 pathways: EDEM for degradation or UUGT for reentry into CNX cycle. A glycoprotein with permanent structural defects is modified by the slow-acting enzyme ER mannosidase I. This enzyme attaches Man8 glycans to misfolded glycoproteins and in so doing generates a signal that results in ER-associated glycoprotein degradation (GERAD). A glycoprotein with a glycan in the form Glc0-3Man8GlcNAc2 is released from the calnexin cycle, recognised by a mannosidase- like protein EDEM and dislocated from the ER to the cytosol. Here the protein binds to the glycan-specific F box protein Fbx2 and is targeted to the SCF-Fbx2-type E3 ubiquitin ligase complex. This results in the protein being polyubiquitinated. The protein is subsequently deglycosylated by a cytosolic peptide N-glycanase (PNGase) that is closely associated with the ubiquitin ligase complex and/or the 19S lid of the proteasome. Finally, the ubiquitinated, deglycosylated protein is degraded by the proteasome. (This definition may be outdated - see the DesignNote.)
A 9-residued peptide vaccine consisting of amino acids 157 through 165 of the cancer/testis (CT) antigen ESO-1. Modified at position 165 (cysteine to valine) to improve immunogenicity, ESO-1:157-165(165v) peptide administered as a vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for ESO-1, resulting in decreased tumor growth. ESO-1 is expressed in a variety of cancers, including melanoma, breast, bladder, prostate, and hepatocellular cancers. (NCI04)
Expression of a fusion protein that results from a t(3;21)(q26;q22) translocation, which involves the human genes EVI1 and RUNX1 and is associated with chronic myelogenous leukemia.
An antisense oligonucleotide that targets the type 8 form of EWS/FLI-1, an oncogenic fusion gene found in Ewing's sarcoma and primitive neuro-ectodermal tumor that results from a t(11;22) chromosomal translocation. EWS/FLI 1 type 8 antisense oligonucleotide inhibits the expression of the EWS/FLI 1 type 8 gene and/or the translation of EWS/FLI 1 type 8 mRNA, thereby down-regulating the abnormal transcription factor and inhibiting tumor cell growth and tumorigenicity. (NCI04)
Eicosanoid Degradation consists of conjugation, transport, and/or oxidation of hormone-like endogenous unsaturated and oxygenated fatty acid derivatives of arachidonic acid (eicosanoids) that act near the site of synthesis and have a specific regulatory effect on the activity of target cells in host defense reactions, immediate hypersensitivity, and inflammation. Eicosanoids include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds.
Any agent or mixture of agents that are used to replenish electrolytes in body fluids, such as sodium, potassium, calcium, magnesium, phosphorus, chloride and bicarbonate.
A mixture containing electrolytes used to prevent or treat electrolyte imbalance that can be caused by abnormal levels of sodium, magnesium, phosphate, chloride, bicarbonate and/or potassium. Severe electrolyte disturbances can cause cardiac and neurological problems, organ failure and eventually death.
A morphologic finding that refers to microvascular proliferation that resembles glomeruloid structures. It is seen in gliomas.
A process that involves the non-covalent binding of glucogon to the glucogon receptor. This interaction plays a role in the initiation of a Gs protein-dependent signaling cascade, which modulates both blood glucose levels and gluconeogenesis.
Glucose Transport Induction consists of the initiation of subcellular or molecular processes directly involved in the physical translocation from one site or compartment to another (typically, extracellular to intracellular) of the simple C6H12O6 monosaccharide, glucose, that acts as an energy source for cells.
Glucose Transport Inhibition involves interference with, or restraint of, subcellular or molecular processes directly involved in the physical translocation from one site or compartment to another (typically, extracellular to intracellular) of the simple C6H12O6 monosaccharide, glucose, that acts as an energy source for cells.
Any substance that inhibits glucosidase, specifically alpha-glucosidase in the brush border of the small intestines, an enzyme that catalyzes the breakdown of carbohydrates to simple sugars. Inhibition of glucosidase reduces and delays the effects of ingested carbohydrates on blood sugar.
Any substance that inhibits glucuronidase, an enzyme involved in the hydrolysis of glucuronic acid from glucuronides. One of the key processes by which the human body eliminates toxic chemicals and hormones is by glucuronidation. When beta-glucuronidase deconjugates these glucuronides, it prolongs the stay of the hormone or toxic chemical in the body. Inhibition of glucuronidase can produce chemoprotective effects.
Any substance that inhibits glutamine amidotransferase, an enzyme that catalyzes the removal of the ammonia group from glutamine and transfers it to another substrate. Inhibition of glutamine amidotransferase inhibits de novo purine synthesis and results in inhibition of DNA synthesis and cell cycle arrest.
Any substance that inhibits glutathione transferase, an enzyme that catalyzes the addition of a glutathione moiety to a substrate and is involved in detoxification of endogenous and exogenous compounds. Inhibition of glutathione transferase can increase the half-life and activity of chemotherapeutic agents.
Any substance that inhibits glycinamide ribonucleotide formyltransferase, the first folate dependent enzyme in de novo purine synthesis. Inhibition of glycinamide ribonucleotide formyltransferase causes purine depletion and results in inhibition of DNA synthesis and cell cycle arrest.
A process that involves the binding of glycine to a glycine receptor. These interactions are involved in various activities, including synaptic plasticity, learning, memory and inhibition of neurotransmission.
Serine is derived from 3-phospho-D-glycerate, an intermediate of glycolysis, and glycine is derived from serine. Threonine is an essential amino acid, which animals cannot synthesize. In bacteria and plants, threonine is derived from aspartate.
An uncommon, usually aggressive adenocarcinoma of the breast characterized by the presence of clear cells that contain glycogen.
Glycolysis is the process of converting glucose into pyruvate and generating small amounts of ATP (energy) and NADH (reducing power). It is a central pathway that produces important precursor metabolites: six-carbon compounds of glucose-6P and fructose-6P and three-carbon compounds of glycerone-P, glyceraldehyde-3P, glycerate-3P, phosphoenolpyruvate, and pyruvate. Acetyl-CoA, another important precursor metabolite, is produced by oxidative decarboxylation of pyruvate. When the enzyme genes of this pathway are examined in completely sequenced genomes, the reaction steps of three-carbon compounds from glycerone-P to pyruvate form a conserved core module, which is found in almost all organisms and which often corresponds to operon structures in bacterial genomes. Gluconeogenesis is a synthesis pathway of glucose from non-carbohydrate precursors. It is essentially a reversal of glycolysis with minor variations of alternative paths.
In glycolysis, the six-carbon sugar glucose is oxidized and split in two halves, to create two molecules of pyruvate (3 carbons each) from each molecule of glucose. Along the way, the cell extracts a relatively small amount of energy from glucose in the form of ATP, 2 ATP molecules collected for each glucose molecule that starts down the glycolytic path. The pyruvate produced has one of three metabolic fates, to either become acetyl-CoA, ethanol, or lactate. When oxygen is available, the pyruvate can be converted to acetyl-CoA and enter the Krebs Cycle, where the acetyl-CoA will be completely oxidized and generate ATP through oxidative phosphorylation. Fermentation is much less efficient than oxidative phosphorylation in making ATP, creating only 2 ATP per glucose while oxidative phosphorylation creates 36 ATP per glucose in mammalian cells. Oxidative phosphorylation does not work in the absence of oxygen, however, and in the absence of oxygen glycolysis is forced to a halt due to a lack of NAD+, unless NAD+ is regenerated through fermentation. In mammalian muscle, strenuous exertion can create conditions in which oxygen is consumed faster than blood can provide it, forcing the muscle to use fermentation and create lactic acid; it is the lactic acid that makes your muscles sore after a workout. There are ten enzymes that catalyze the steps in glycolysis that convert glucose into pyruvate, and the entire pathway is located in the cytoplasm of eukaryotic cells. The activity of the pathway is regulated at key steps to ensure that glucose consumption and energy production match the needs of the cell. The steps along the pathway each involve a change in the free energy of the products and reactants, and as long as the overall change in free energy is negative, the reaction continues forward, like water flowing down hill to its lowest energy point. The key steps in the regulation of glycolysis, or any pathway, are those that catalyze the rate-limiting, irreversible steps along the pathway. In glycolysis in mammals, the key regulatory enzyme is phosphofructokinase, which catalyzes the rate-limiting committed step. Phosphofructokinase is activated by AMP and inhibited by ATP, among other regulatory mechanisms. Thus, when ATP is low (and AMP is high), phosphofructokinase will be activated and generate more ATP. Similarly, when ATP is abundant, phosphofructokinase will be inhibited to prevent wasting glucose on making energy when it is not needed. Failure to provide energy can have lethal consequences for cells - the absence of oxygen caused by a stroke or a heart attack that prevents ATP generation can have lethal consequences for the cells involved. Cancer cells often generate energy through glycolytic fermentation more than oxidative phosphorylation, suggesting that manipulation of metabolism may provide a therapeutic strategy. Well known glycolytic enzymes such as glyceraldehyde-3-phosphate dehydrogenase may play roles in other cellular processes such as apoptosis. (This definition may be outdated - see the DesignNote.)
The biosynthesis pathway of N-glycans is a costly system with respect to the number of enzymes that are involved in the synthesis and trimming of N-glycans. While the structural diversity of N-glycans in mature proteins in the cell surface is introduced by glycosyltransferases in the Golgi complex, the core glycans in the ER are universal from yeast to mammal and have been considered as intermediates. (This definition may be outdated - see the DesignNote.)
Cell surface proteins can be attached to the cell membrane via the glycolipid structure called glycosylphosphatidylinositol (GPI) anchor. Hundreds of GPI-anchored proteins have been identified in many eukaryotes ranging from protozoa and fungi to mammals. All protein-linked GPI anchors share a common core structure, characterized by the substructure Man (a1-4) GlcN (a1-6) myo-inositol-1P-lipid. Biosynthesis of GPI anchors proceeds in three stages: (i) preassembly of a GPI precursor in the ER membrane, (ii) attachment of the GPI to the C-terminus of a newly synthesized protein in the lumen of the ER, and (iii) lipid remodeling and/or carbohydrate side-chain modifications in the ER and the Golgi. Defects of GPI anchor biosynthesis genes result in a genetic disorder, paroxysmal nocturnal hemoglobinuria.
A Danish brand name for a laxative product containing glycerin and docusate sodium. As a hyperosmotic laxative, glycerin draws water into the bowel from surrounding tissues, thereby softening the stool and increasing bowel action. Docusate sodium acts as a surface-active agent (emollient) that promotes the mixing of intestinal liquid and dry stool. (NCI04)
Any agent that inhibits golgi alpha-mannosidase II, a mannose-trimming enzyme that is the final hydrolase in the N-glycosylation pathway. Inhibition of golgi alpha-mannosidase II decreases the formation of carbohydrate structures required for cell-cell adhesion.
1) To direct or use toward the Golgi apparatus as a target. Targeting of the Golgi apparatus by specific substances to disrupt or alter its function. 2) Related to structural elements in a protein, such as a peptide sequence, that directs the localization of a protein or protein complex to the Golgi apparatus.
A primary endometrioid adenocarcinoma of the endometrium that contains equal to or less than 5% non-squamous solid areas.
A primary mucinous adenocarcinoma of the endometrium that contains equal to or less than 5% non-squamous solid areas.
An immature teratoma that arises from the ovary and is characterized by the presence of rare foci of immature neuroepithelial tissue that occupy less than one low power field (40x) in any slide. (adapted from WHO 2003)
A primary endometrioid adenocarcinoma of the endometrium that contains 6-50% non-squamous solid areas.
A primary mucinous adenocarcinoma of the endometrium that contains 6-50% non-squamous solid areas.
An immature teratoma that arises from the ovary and is characterized by the presence of foci of immature neuroepithelial tissue that occupy one to three low power fields (40x) in any slide. (adapted from WHO 2003)
A primary endometrioid adenocarcinoma of the endometrium that contains more than 50% non-squamous solid areas.
A primary mucinous adenocarcinoma of the endometrium that contains more than 50% non-squamous solid areas.
An immature teratoma that arises from the ovary and is characterized by the presence of large amounts of immature neuroepithelial tissue that occupy more than three low power fields (40x) in any slide. (adapted from WHO 2003)
An atypical meningioma which may recur in approximately 29-40% of the cases. This category includes the atypical meningioma, chordoid meningioma, and clear cell meningioma.
A benign meningioma which may recur in approximately 7-20% of the cases. This category includes the angiomatous meningioma, fibrous meningioma, lymphoplasmacyte-rich meningioma, meningothelial meningioma, metaplastic meningioma, microcystic meningioma, psammomatous meningioma, secretory meningioma, and transitional meningioma.
Growth hormone plays a major role in regulating growth during childhood and adolescence and also regulates metabolism. Defects in growth hormone signaling can result in dwarfism and decreases in growth hormone levels with age have been suggested to play a role in the reduced function of some physiological systems. Growth hormone signals a response in cells through the growth hormone receptor, a member of the cytokine receptor gene family. Growth hormone causes the receptor to dimerize, activating the JAK2 protein kinase. The activity of JAK2 mediates many of the downstream responses to growth hormone through phosphorylation of STAT transcription factors, MAP kinases, other kinase cascades and molecules involved in metabolism like IRS-1. Factors like SOCS and SHP-1 appear to play a role in the down regulation of signaling by growth hormone and cytokines. (This definition may be outdated - see the DesignNote.)
An immunotoxin comprised of an anti-CD7 antibody, HB-2, linked to Saporin, a toxin that inhibits protein synthesis, eliciting an antibody-dependent cellular immunity response. (NCI)
Hepatitis B is a small DNA virus that contains only 4 open reading frames in its genome. Three of these ORFs have been identified as the envelope, capsid and polymerase genes, while the function of the fourth has remained unknown until recently. The fourth reading frame has been called the X gene and produces HBx protein that is essential for viral replication in liver cells and acts broadly to activate a variety of transcription factors. One hypothesis of HBx activity has been that it enters the nucleus to act as a transcriptional regulator. One piece of evidence supporting this mechanism of HBx action is that HBx interacts with the transcription factor CREB and increases its DNA-binding activity. This mechanism does not explain all of the effects of HBx however. Another hypothesis for the HBx mechanism of action is that HBx increases calcium release into the cytoplasm. This mechanism of action is consistent with the variety of transcription factors and kinases affected by HBx since calcium signaling affects many different signaling pathways. HBx does not appear to interact directly with Ras or protein kinases but does appear to activate the calcium activate protein kinase Pyk2. A dominant negative form of Pyk2 blocks HBx activity and the involvement of calcium in HBx activation of Pyk2 is indicated by the action of several molecular probes that alter cytosolic calcium signaling. BAPTA-AM chelates cytosolic and blocks HBx action. Cyclosporin A blocks mitochondrial calcium signaling and also blocked HBx signaling. CGP37157 is a compound that blocks the mitochondrial sodium calcium pump and also blocks hepatitis B viral replication, indicating that mitochondrial calcium signaling is the target of HBx function. Compounds that elevate cytoplasmic calcium levels (valinomycin and thapsigargin) increase the rate of replication of viruses that lack HBx, further supporting the role of HBx as an inducer of intracellular calcium signaling. The mechanism by which HBx causes calcium release is not yet known. Src activation appears to induce viral replication while Ras signaling does not, suggesting that the activation of Ras signaling by HBx may play a distinct function, perhaps the induction of cancer. (This definition may be outdated - see the DesignNote.)
A vaccine comprised of autologous dendritic cells pulsed with HER2/neu intracellular domain protein to induce a T-cell response.
HIV infection leads to drastic declines in CD4 T helper cells, in part through apoptosis of uninfected cells. Apoptosis of uninfected cells may be induced through the expression of Fas ligand on the surface of HIV-infected cells, stimulating the Fas-dependent apoptotic pathway in cells that come in contact with infected cells. The NEF protein expressed by HIV may play a role in the inducing the expression of Fas-ligand by infected cells. If this is the case, then a question that arises is how infected cells themselves escape Fas-mediated apoptosis. The NEF protein appears to play a role in this process as well. NEF interacts with the ASK1 kinase (apoptosis signal-regulating kinase) involved in apoptotic signaling by TNF and Fas-ligand. Interaction of NEF with ASK1 prevents phosphorylation of downstream MAP kinases and JNK kinases involved in apoptotic signaling. (This definition may be outdated - see the DesignNote.)
HIV Budding is a process in which newly generated viral RNA and protein complexes are assembled at, packaged in, and released from the cell surface membrane taking a piece of the cell membrane to form their own viral membranes. To bud from infected cells, HIV-1 employs several host proteins such as endosomal sorting protein Tsg101, which functions in the Vps pathway. The L domain (PTAP) in the p6 domain of HIV-1 Gag interacts with the N-terminal domain of TSG101; the Vps28-binding domain of TSG101 inhibits budding.
HIV infection is associated with immunosuppression caused by a dramatic reduction in the helper T cell population. The loss of helper T cells may be caused by HIV-induced apoptosis of both infected and uninfected helper T cells. HIV uses the CCR5 chemokine receptor as a coreceptor for macrophage cell entry and upregulates fas-ligand on these cells. CD4 on helper T cells is essential for viral cell entry and infection. Cross-linking of CD4 on the T cell surface may be involved in upregulation of Fas and sensitization of T cells to apoptosis induced by the Fas/Fas-ligand interaction. (This definition may be outdated - see the DesignNote.)
A vaccine containing one or more peptides derived from the human immunodeficiency virus (HIV). As a vaccine antigen, an HIV peptide may stimulate the host immune response against HIV, thereby preventing or treating HIV infection. (NCI04)
A synthetic HIV vaccine based on a recombinant canary pox virus vector expressing the human immunodeficiency virus (HIV) glycoprotein gp160. HIVgP160 vaccine has been used to generate in vivo primary T lymphocyte response against HIV antigens. (NCI04)
A vaccine directed against Human Papillomavirus Type 11 that causes majority of the genital warts and anogenital cancers. (NCI)
A peptide derived from the oncogenic human papillomavirus (HPV) early gene product E6. The HPV 16 transforming protein E6 is expressed in precancerous and malignant cervical lesions and has a high affinity for the most common human lymphocyte antigen (HLA), HLA-A2. Immunogenic peptides from the HPV 16 E6 may be used to trigger a T-cell-mediated immune response to HPV. (NCI04)
A vaccine consisting of human papillomavirus-derived noninfectious virus-like particles (VLPs), containing the L1 major capsid protein. Vaccination with HPV 16 L1-VLP results in increases in T cell-proliferative response to HPV 16 L1-VLP, as well as significant increases in cytokine (interferon-gamma, interleukin-5 and -10) responses to L1 VLP. This agent may reduce the incidence of persistent HPV-16 infection, which may be responsible for half of all cases of cervical cancer including high-grade cervical intraepithelial neoplasia. (NCI04)
A synthetic peptide vaccine consisting of amino acids 13 through 21 of the viral oncoprotein human papillomavirus (HPV) 18 E6. The HPV 18E6 peptide cross-reacts immunologically with both HPV type 16 and HPV type 18, the most common HPV types involved in cervical cancer. Vaccination with HPV-18 E6:13-21 peptide may stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells positive for HPV 16 and 18.
A molecular genetic abnormality indicating the presence of multiple copies of the FGF4 gene.
Hematopoiesis Inhibition involves interference or restraint of a process of blood formation; more specifically formation of blood cells that are all derived from hematopoietic stem cells.
The process of hematopoiesis is regulated by various cytokines. The combination of cytokines stimulates the proliferation and/or differentiation of the various hematopoietic cell types. Bone marrow stromal cells are the major source of hematopoietic cytokines in the non-infectious state. In the presence of infection, cytokines produced by activated macrophages and TH cells induce hematopoietic activity. The induction by cytokines results in rapid expansion of the population of white blood cells to fight infection. (This definition may be outdated - see the DesignNote.)
Neoplasms of the hematopoietic system, including hematopoietic cell neoplasms (e.g. leukemias, lymphomas) and non-hematopoietic cell neoplasms that can affect the hematopoietic system (e.g. lymph node and splenic sarcomas). --2003
The function of hemoglobin in oxygen transport by red blood cells requires precise assembly of a tetramer of two beta-subunits and two alpha-units. If too many beta-subunits are present, then all tetramers of beta-subunits are formed that bind oxygen but do not release it when needed. When alpha-subunits are in excess they form precipitates with oxidized heme that damage red blood cells. Red blood cells require a precise coregulation of alpha and beta subunit expression to maintain the proper ratio of the subunits and normal red blood cell function. Generally red blood cells express slightly more alpha than beta-subunits to avoid forming unproductive beta-tetramers (HbH). The slight excess of alpha units are blocked from precipitation by a molecular chaperone, AHSP, alpha-hemoglobin stabilizing protein. Expression of the AHSP gene is coordinately activated with the globin genes and heme biosynthesis genes by the GATA-1 gene involved in erythrocyte differentiation. AHSP blocks precipitation of alpha-units, and promotes the formation of normal productive alpha-beta tetramers (HbA). People with mutation or deletion of the beta-subunit gene have Beta-thalassemias resulting from an over-abundance of alpha subunits and their precipitation. The severity of the phenotype may depend on the AHSP genotype of these individuals and elevating AHSP levels through gene therapy may provide a treatment strategy for beta-thalassemia. (This definition may be outdated - see the DesignNote.)
Passage or transfer, as of a disease, affecting recipients who suffer from hemophilia. (NCI)
Heparan Sulfate Biosynthesis consists of cellular enzymatic reactions that produce heparan sulfate, a glycosaminoglycan of repeating disaccharide units, in most cell plasma membranes. Heparan Sulfate accumulates in several mucopolysaccharidoses.
The processes which result in cancers in the liver.
Agents administered before, with, or after cancer therapy to reduce or prevent damage or toxicity to the liver. (NCI)
Fallopian tube carcinoma that has developed in relatives of patients that have a history of fallopian tube carcinoma.
Heterodimerization involves a biophysical interaction between two dissimilar biological molecules or subunits, such as between two proteins. The interaction is often mediated by a biophysical interaction between one or more specific domains within each subunit and, typically, significantly influences the function of each subunit.
The presence of genomic instability associated with defective DNA mismatch repair in greater than 30% of the microsatellite instability (MSI) biomarkers in a tumor sample.
A high grade B-cell lymphoma showing greater pleomorphism in nuclear size and shape than the classical Burkitt lymphoma.
A precancerous neoplastic process that affects the cervical squamous epithelium. It is usually associated with human papillomavirus infection. It is classified as cervical squamous intraepithelial neoplasia 2 when there is nuclear atypia in both the upper and lower epithelial layers, mitotic figures are confined to the basal two-thirds of the epithelium, and maturation is present in the upper half of the epithelium. It is classified as cervical squamous intraepithelial neoplasia 3 when there is nuclear atypia and mitotic figures throughout the entire thickness of the epithelium, and maturation is absent or confined to the upper third of the epithelium.
A papillary transitional cell carcinoma of the urinary bladder, characterized by marked architectural and cytologic abnormalities and frequent mitotic figures (at all levels of the urothelium). This type of carcinoma is commonly associated with invasive disease at the time of presentation.
High grade prostatic intraepithelial neoplasia characterized by the presence of large glands with papillary infoldings that contain cells with xanthomatous cytoplasm.
High grade prostatic intraepithelial neoplasia characterized by the presence of secretory cells with their nuclei polarized towards the lumen of the glands.
High grade prostatic intraepithelial neoplasia characterized by the presence of masses of mucin within the affected distended glands.
High grade prostatic intraepithelial neoplasia characterized by the presence of signet ring cells in the affected glands.
High grade prostatic intraepithelial neoplasia characterized by the presence of small neuroendocrine cells in the affected glands.
Cancer that is likely to recur (come back), or spread.
Histamine Degradation consists of conjugation, transport, oxidation, or enzymatic breakdown of a decarboxylation product of histidine (histamine), found particularly in mast cells and basophils, and involved in capillary dilation and permeability; blood pressure decrease; smooth muscle contraction; gastric secretion; heart rate acceleration; immediate hypersensitivity; and central neurotransmission.
A process that involves the non-covalent binding of histamine to one of four known histamine receptor proteins. These interactions play a role in signaling pathways that modulate vasodilation, neurotransmitter release, gastric acid secretion, neutrophil release and smooth muscle contraction and relaxation.
Any substance that inhibits histone deacetylase, an enzyme that catalyzes the removal of acetyl groups from core histones. Inhibition of histone deacetylase can result in hyperacetylation of histones, with an effect on gene expression and cell differentiation.
Homodimerization involves a biophysical interaction between two identical biological molecules or subunits, such as proteins. The interaction is often mediated by a biophysical interaction between one or more specific domains within the subunits and, typically, significantly influences the function of the subunits.
A region on a chromosome which, when stained, is uniform in appearance. (Normally, a stained chromosome shows a banding pattern.) Homogeneously staining regions contain multiple copies of a single gene. (Online Medical Dictionary)
Synthetic female sex hormones mixture administered either orally or transdermally to maintain adequate levels of estrogen in women with diminished circulating sex hormones. Hormone replacement preparation is usually given to menopausal women to alleviate menopausal symptoms, including hot flashes, night sweats, irregular menstruation, fat redistribution, mood swings, sleep disorders, vaginal dryness and to prevent osteoporosis. The preparation usually contains conjugated estrogens, estradiol, or estrone sulfate and a progesterone derivative, such as medroxyprogesterone, norgestimate or norethindrone, which is used to offset an increased risk of estrogen-induced endometrial cancer.
Heterologous antisera to mouse lymphocytes produced in horses and used to treat or prevent transplant rejection. These polyclonal antisera produced by immunization of horses with mice splenocytes exhibit some general anti-leucocyte activity as well as some antiplatelet activity and may produce varying degrees of leucopenia or thrombocytopenia; the primary effect of anti-lymphocyte antisera is to reduce the T-lymphocyte count. Antibodies directed against lymphocytes are among the most potent immunosuppressive agents available for organ transplantation. (NCI04)
An immunoconjugate comprised of a humanized monoclonal antibody with antitumor activity. The monoclonal antibody CC49 is developed from the murine monoclonal antibody B72.3 and is humanized by grafting the hypervariable regions onto the variable light (VL) and variable heavy (VH) frameworks of the monoclonal antibodies LEN and 21/28' CL. In addition the CH2 domain in the constant region is deleted to increase plasma clearance. The resultant antibody binds to the pancarcinoma tumor-associated glycoprotein (TAG)-72 with high affinity. Furthermore, the antibody is conjugated to PA-DOTA, a bifunctional chelating agent and commonly radiolabeled, resulting in an effective agent for radioimmunotherapy.
An infectious process caused by the human herpesvirus 8. This infection is associated with Kaposi sarcoma.
A human monoclonal immunoglobulin M (IgM) antibody with potential antineoplastic activity. Human MOAB LICO 28a32 binds to the colon tumor-associated antigen 28A32 (CTAA 28A32) found on the cell surface and in the cytoplasm of colon carcinoma cells. (NCI04)
A recombinant vaccine of different types of HPV proteins which are well-conserved within types with a significant inter-type variation.
A salt that is comprised of a hydrogen and chloride ion that can be linked to a base form of a drug making it water-soluble. (NCI)
A semisynthetic, high viscosity polymer used as a food additive which may have the ability to lower total cholesterol and low-density lipoprotein cholesterol (LDL-C).
A radioimmunoconjugate of a murine monoclonal antibody (MoAb) COL1, labeled with iodine 131 (I-131). COL1 recognizes an epitope of carcinoembryonic antigen (CEA), which is over-expressed in many tumor cell types. I-131 MoAb COL1 delivers beta and gamma radiation emitting I-131 nuclide directly to tumor cells that express CEA, thereby allowing imaging and/or treatment of cancers.
IGF-1R, the type 1 receptor for insulin-like growth factor, mediates cell survival and growth in response to its ligands IGF-1 and IGF-2. This tyrosine kinase receptor is widely expressed in many cell types and is a key mediator of growth. Overexpression or activation of IGF-1R may be involved in the proliferation of transformed cells, making inhibition of IGF-1R signaling a strategy for the development of cancer drugs. IGF-1R activates three signaling pathways that converge to phosphorylate BAD protein and block apoptosis. The first pathway activated by IGF-1R stimulates PI3-kinase and the AKT pathway to phosphorylate BAD and block apoptosis. A second pathway activated by IGF-1R involves ras mediated activation of the map kinase pathway to block apoptosis. A third pathway involves interaction of raf with mitochondria in response to IGF-1R activation. The convergence of these pathways to block apoptosis may enhance the IGF-1R response. (This definition may be outdated - see the DesignNote.)
IL-10 is a cytokine with potent anti-inflammatory properties, repressing the expression of inflammatory cytokines such as TNF-alpha, IL-6 and IL-1 by activated macrophages. The IL-10 receptor is in the JAK/STAT class of receptors but activation of the JAK/STAT pathways by IL-10 does not appear on its own to be responsible for the anti-inflammatory properties of this cytokine. The anti-inflammatory actions of IL-10 appear to require induction of the enzyme heme oxygenase-1 (HO-1) through a map kinase pathway involving the p38 kinases. HO-1 is involved in the biosynthesis of heme, and catalyzes a reaction producing carbon monoxide, free iron, and the heme precursor biliverdin. HO-1 is induced by IL-10 and is also induced by oxidative stress. Blocking HO-1 with inhibitors or antisense blocks the anti-inflammatory actions of IL-10. The anti-inflammatory actions of HO-1 appear to be the result of signaling by the carbon monoxide it produces since removal of CO blocks the anti-inflammatory action of IL-10 and HO-1. The anti-inflammatory actions of IL-10 may be therapeutically useful either directly or through modulation of HO-1 activity. (This definition may be outdated - see the DesignNote.)
The IL-2 receptor is a key component of immune signaling and is required for the activation, proliferation, and survival of T cells. This receptor is composed of three polypeptide chains, the alpha, beta, and gamma chains. The IL-2 receptor gamma chain is a common component for several other cytokine receptors, including IL-4, IL-7, IL-9 and IL-15. The IL-2 receptor beta chain is essential for IL-2 signaling and is also a component of the IL-15 receptor complex. The polypeptides of the IL-2 receptor do not themselves have intrinsic catalytic activity, but interact with cytoplasmic signaling proteins to transduce signals. Different regions of the cytoplasmic domain of the IL-2 receptor beta chain interact and couple with distinct signaling pathways and cellular responses. JAK1 associates with the beta chain and JAK3 with the gamma chain. Binding of IL-2 induces heterodimerization of receptor subunits, and activation of JAK kinase activity. Tyrosine residues in the beta chain cytoplasmic domain are phosphorylated during activation, recruiting other factors to the phosphorylated tyrosine residues through src homology 2 (SH2) domains. The adaptor protein Shc binds to phosphorylated tyrosine 338 of the beta chain. When bound, Shc is phosphorylated and couples through Grb2 and Sos-1 to activate Ras and stimulate T cell proliferation. Another key proliferative pathway activated by IL-2 is phosphorylation of STAT-5 by JAK kinases. STAT-5 is recruited to IL-2 beta phosphorylated tyrosines at multiple positions, including Y338, Y392 and Y510. Once phosphorylated, STAT-5 enters the nucleus to regulate the transcription of several genes, some proliferative, such as cyclin genes, and others that are involved in T cell immune function such as cytokine genes. The suppressors of cytokine activation, SOCS-3 and SOCS-1, oppose phosphorylation and activation of STAT-5 and JAK1 caused by IL-2. PI3 kinase is another protein recruited to IL-2 receptor beta chain tyrosines when phosphorylated. Activation of PI3 Kinase also contributes to the proliferative activity of IL-2 in T cells. The role of other tyrosines in the IL-2 receptor beta chain, Y355, Y358 and Y361, is not yet clear, but may be involved in signaling by the protein kinase p56lck. In addition to stimulating T cell activation and proliferation, IL-2 activation blocks T cell apoptosis through multiple pathways. Among the genes activated by STAT-5 are BCL-xL, an inhibitor of apoptosis, and fas-ligand, an activator of apoptosis in cells expressed the fas receptor. PI3 kinase also contributes to anti-apoptotic activity of IL-2 through AKT activation. T cell responses to IL-2 must be coordinated in part in the complex protein-protein interactions with the IL-2 receptor beta chain. (This definition may be outdated - see the DesignNote.)
A state of ill health caused by medical treatment, usually due to mistakes made in treatment.
An immunotoxin of monoclonal antibody (MoAb) RFB4 covalently linked to a single deglycosylated ricin toxin A-chain (dgA), originated from castor beans. MoAb RFB4 recognizes CD22 antigen, a B-cell adhesion protein expressed on malignant cells in about 70 percent of non-Hodgkin lymphoma and chronic lymphocytic leukemia. Ricin toxin A-chain, a potent protein synthesis inhibitor, was deglycosylated and was used in this immunoconjugate to avoid hepatic entrapment. This immunotoxin was conjugated through SMPT linker, which confers a slower breakdown of the toxin, and limits specific cytotoxicity of ricin toxin to CD22-positive malignant cells.
A process that involves the binding of an immunoglobulin on the surface of a B cell to a cognate antigen on the surface of a follicular dendritic cell, resulting in a strong survival signal for the immunoglobulin-bearing cell. These interactions are involved in activation, proliferation and maturation of selected B cells and apoptosis of non-selected populations.
Immunologic Factor Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction and often spatial complementarity with antibody or cytokine proteins that affect immune functions, immune responses, or inflammation.
A purified Norwegian Beta-Glucan (NBG), extracted from the cell walls of baker's yeast. Used as an immunostimulant in complementary medicine, NBG binds specifically to receptors found on the surface of specialized macrophages, granulocytes and natural killer cells and may stimulate these cells to become more active in engulfing and digesting foreign antigens; NBG also induces the production of cytokines that further augment the host immune response to foreign antigens. Use of this agent may enhance overall resistance to infectious agents and promote wound healing and tissue repair. (NCI04)
Impaired Cell Membrane Integrity consists of activities that interfere with, or restrain, fabrication, construction, or maintenance of the regular structure and function of semipermeable lipid bilayer membranes that surround or reside within a cell.
An alkylsulfonate alkylating agent that cross-links with DNA, causing inhibition of DNA synthesis.
A humanized IgG1 form of the mouse monoclonal antibody (MoAb) anti-Tac with anti-leukemic activity. This MoAb recognizes human IL-2 receptor alpha chain (CD25) and blocks the interaction of IL-2 with IL-2 receptor, and thus prevents activation of T-cells in some leukemia and lymphomas as well as some autoimmune disorders. In addition, this antibody is radiolabeled with gamma emitting radionuclide Indium-111, thereby targeting the Indium radioisotope to the cancer cells which results in non-repairable DNA double-stranded breaks and subsequent cell death.
A poxvirus made non-infectious by ultraviolet light or other inactivation methods in order to reduce its pathogenicity. In cancer gene therapy, inactivated vaccinia virus may be used as a vector to express a protein that kills tumor cells or elicits specific anti-tumor immunity. In a cancer vaccine application, tumor cells taken from the host may be adsorbed with inactivated vaccinia virus and returned to the host, where the modified tumor cells may stimulate an anti-tumor immune response. (NCI04)
A genetic finding indicating that there is increased activation of the NFkappaB pathway.
A record of a patient's medical background regarding the occurrence of cancer and cancer-related problems.
An Epstein-Barr virus negative disorder with a chronic clinical course affecting predominantly adults and characterized by the proliferation of large granular lymphocytes with natural killer cell immunophenotype. The T-cell receptor genes are not rearranged.
An invasive transitional cell carcinoma of the bladder characterized by the presence of clear cells.
An invasive transitional cell carcinoma of the bladder that exhibits spindle cell sarcomatoid features.
An invasive transitional cell carcinoma of the bladder that exhibits glandular differentiation.
An invasive transitional cell carcinoma of the bladder that exhibits squamous differentiation.
A microscopic finding indicating that the neoplastic cells exhibit an infiltrating growth in a tumor sample.
A rare neoplasm that arises from the inner ear. Representative examples include lipoma and acoustic schwannoma.
Any substance that inhibits inosine monophosphate dehydrogenase, an enzyme that catalyzes the conversion of inosine monophosphate to xanthosine monophosphate, the rate-limiting step in the de novo biosynthesis of guanine nucleotides. Inhibition of inosine monophosphate dehydrogenase can lead to inhibition of cell proliferation.
The chemical reactions and pathways involving inositol phosphate, 1,2,3,4,5,6-cyclohexanehexol, with one or more phosphate groups attached. [CHEBI:24848, GOC:jl]
The appropriate signaling through the insulin pathway is critical for the regulation of glucose levels and the avoidance of diabetes. Insulin forms a complex with the insulin receptor (IR) and b chains to form the active signaling complex. Through recruitment of adaptor molecules and the activation of RAS, the activated IR can cause transcriptional activation. (This definition may be outdated - see the DesignNote.)
Integrin Inhibition involves interference with, or restraint of, the activities of a family of noncovalent heterodimeric transmembrane glycoprotein signal transduction receptors for fibronectin, laminin, and other adhesive extracellular matrix glycoproteins, complement, and other cells. Different alpha and beta complexes vary in ligand-specificity and the intracellular domains interact with cytoskeleton.
Integrins are cell surface receptors that interact with the extracellular matrix and mediate intracellular signals in response to the extracellular matrix including cellular shape, mobility, and progression through the cell cycle. Integrins do not themselves possess a kinase domain or enzymatic activity but rely on association with other signaling molecules to transmit signals. Interactions between the extracellular matrix and the actin cytoskeleton commonly take place at focal adhesions on the cell surface that contain localized concentrations of integrins, signaling molecules, and cytoskeletal elements. Talin forms a direct interaction with the integrin cytoplasmic domain, and interacts with cytoskeletal elements (actin) and signaling factors. Paxillin and CAS also localize in focal adhesions and may serve as a scaffold for other integrin signaling components like FAK and src. Interaction of FAK, CAS and src may be required for integrin regulation of cell cycle progression. The CrkL adaptor protein may regulate downstream integrin signaling. Growth factor signaling pathways and the caveolin receptor exhibit important cross talk with integrin receptors in cellular responses like activation of map kinase, proliferation and motility. (This definition may be outdated - see the DesignNote.)
Signaling by interferon-gamma stimulates anti-viral responses and tumor suppression through the heterodimeric interferon-gamma receptor. Signaling is initiated by binding of interferon-gamma to its receptor, activating the receptor-associated JAK2 tyrosine kinase to phosphorylate STAT transcription factors that activate interferon responsive genes. Molecular chaperones that modulate or alter protein folding interact with different components of the interferon signaling pathway. One chaperone that modulates interferon signaling is hTid-1, a member of the DnaJ family of chaperones and a co-chaperone for the heat shock protein Hsp70, another molecular chaperone. hTid-1 was found in a two-hybrid screen to bind to JAK2 and also to interact with the interferon-gamma receptor. In addition, hTid-1 and JAK2 also interact with Hsp70. Overexpression of hTid-1 represses transcriptional activation by interferon-gamma and Hsp70 dissociates from these proteins when interferon is added to cells, suggesting that Hsp70 holds Jak2 in an inactive conformation prior to ligand activation, and is released in the presence of agonist to allow the activation of Jak-2 and downstream pathways. hTid-1 and Hsp-70 interact with other signaling proteins as well. One of these is Tax, a protein encoded by the HTLV-1 virus that binds to hTid-1. hTid-1 also represses NF-kB activation by blocking the phosphorylation and inactivation of I-kappaB by the IkappaB kinase beta. Hsp70 plays a significant role in protein unfolding for entry into mitochondria and also interacts with tumor suppressor gene products to produce their anti-proliferative activity. One of the actions of interferon is to induce apoptosis of infected target cells, in part through a mitochondrial dependent mechanism. An interaction between interferon signaling and Hsp70 may alter this mitochondrial apoptosis pathway, perhaps playing a role in interferon-mediated apoptosis of infected or transformed cells. The HTLV-1 Tax protein that interacts with Hsp70 blocks mitochondrial induced apoptosis, providing a protection against interferon-mediated cellular defenses. (This definition may be outdated - see the DesignNote.)
An aqueous therapeutic analogue of the endogenous cytokine interleukin-1-beta (IL-1-beta). Produced mainly by monocytes, endogenous IL-1-beta plays a role in hematopoiesis, is a potent stimulator of T-cell activity, and may promote or inhibit tumor growth, depending on tumor type. (NCI04)
A vaccine based on anti-idiotype (Id) monoclonal antibodies combined with interleukin-2 (IL-2). Anti-Id vaccines have been shown to be effective in treatment of B-cell lymphoma in animal models and in clinical trials, resulting in tumor regression; the addition of interleukin-2 (IL-2) may augment the therapeutic effect of anti-Id vaccines. (NCI04)
A glycoprotein cytokine produced by the human leukemia T-cell line Jurkat. As a paracrine factor, IL-2 drives the expansion of antigen- specific cells and stimulates B cell, NK cell and LAK cell activities. (NCI04)
A Sertoli-Leydig cell tumor of the ovary characterized by the presence of spindle-shaped gonadal stromal cells and Sertoli cells, some of which are atypical. Leydig cells are also present forming clusters at the periphery of the cellular aggregates. Metastases have been reported in a minority of patients.
An ovarian Sertoli-Leydig cell tumor of intermediate differentiation, characterized by the presence of a heterologous component, usually consisting of cartilage, skeletal muscle, or rhabdomyosarcoma.
A neoplastic process characterized by the proliferation of spindle to cuboidal myoepithelial cells within small breast ducts.
A malignant neoplasm that arises from the vagina and is characterized by the presence of an epithelial and a mesenchymal component. This category includes adenosarcoma, carcinosarcoma, and malignant mixed tumor resembling synovial sarcoma.
A very rare malignant mixed epithelial and mesenchymal neoplasm that arises from the vagina and resembles synovial sarcoma. It is characterized by a biphasic pattern and is composed of gland-like structures that are lined by epithelial cells and a cellular mesenchymal component.
A malignant neoplasm that arises from sweat glands in the vulva. Representative examples include eccrine adenocarcinoma, apocrine adenocarcinoma, and Paget disease.
Production of a new growth or growths in the mammary gland.
Corepressors are coregulators that interact with transcriptional silencers in a variety of pathways such as cell proliferation, differentiation and apoptosis. Abnormal corepressor-silencer interactions have been implicated in a variety of human disease pathways including several types of leukemia. The regulation of the SMRT corepressor via the p38 and Mek-1 Kinase pathway is represented in this pathway. The EGF receptor represents one mechanism by which SMRT function is inhibited by the tyrosine kinase signaling pathway. The MEKK1 and p38 pathways are activated by EGF resulting in cross-regulation of SMRT. The induction of SMRT phosphorylation by either pathway causes SMRT to unbind from the transcription factor complexes represented by RXR, RAR, T3R and PLZF. (This definition may be outdated - see the DesignNote.)
Specific molecular molecules or signatures that indicate that a cell will become neoplastic at a future time.
Any substance that inhibits matrix metalloproteinase (MMP), an endopeptidase that degrades components of the extracellular matrix during tissue remodeling processes, wound healing, angiogenesis, and tumor invasion.
A ganglioneuroma characterized by the presence of mature ganglion cells and a mature Schwannian stroma.
A ganglioneuroma characterized by the presence of differentiating neuroblasts, maturing and mature ganglion cells.
A tumor that can be accurately measured in size. This information can be used to judge response to treatment.
A nitrogen mustard alkylating agent that causes DNA cross linkages. It is a known carcinogen especially in mice. (NCI)
A synthetic allogeneic cancer vaccine. Melanoma theraccine typically consists of lysed melanoma cells obtained from several melanoma cell lines combined with an adjuvant (such as DETOX or RIBI). This agent may be combined with immunomodulatory cytokines such as interferon alpha. Melanoma theraccine may induce a rise in the level of cytotoxic T-lymphocyte precursors. (NCI04)
A malignant peripheral nerve sheath tumor characterized by the presence of malignant cells that contain melanin and formation of psammoma bodies.
Membrane Fusion Activity involves merging of adjacent structures delimited by lipid bilayer membranes into a single structure.
Posttranslational modification of proteins targeted for membranes.
A gastrointestinal stromal tumor that arises from the mesentery. This is an extragastrointestinal tumor, meaning that it does not arise directly from the gastrointestinal tract.
Metabolite Interaction involves a biophysical interaction with a biological metabolite.
A tumor arising at a location distant to the primary lesion.
The carbon chains of methionine, isoleucine, threonine, and valine are broken down to produce succinyl-CoA, which feeds into the Citric Acid Cycle. Methionine donates its methyl group via S-adenosylmethionine to one of several acceptors and the four remaining carbons are the backbone of propionyl-CoA that is subsequently converted to succinyl-CoA. The transdeamination and decarboxylation of valine are followed by a series of steps resulting in the formation of propionyl-CoA. Isoleucine also undergoes transdeamination, followed by oxidative decarboxylation. These steps yield propionyl-CoA as well as acetyl-CoA. Deficiency in the steps that convert isoleucine to propionyl-CoA causes sudden unexplained infant death, Reye-like syndrome, cardiomyopathy, and skeletal myopathy. (This definition may be outdated - see the DesignNote.)
A systemic administered polymeric micelle containing paclitaxel that may be used for chronic inflammatory diseases, such as rheumatoid arthritis and psoriasis. Paclitaxel, a toxoid, binds to and stabilizes tubulin and inhibits the disassembly of microtubules, thereby inhibiting cell division. Paclitaxel also inhibits metalloproteinase, thereby blocking the activities of matrix metalloproteinases (MMPs) and preventing collagen degradation in cartilage and bone.
A tiny cyst that is usually identified by microscopic examination in a tissue specimen.
Metastasis in the form of small clusters of malignant cells identifiable only under the microscope.
Having a relatively minor degree of severity. For quantitative traits, a deviation of between two and three standard deviations from the appropriate population mean.
The incorporation of minerals and electrolytes in coenzymes and gradients.
Chemicals which protect normal cells from the effects of chemotherapy.
The oxidation of fatty acids is an important source of energy for ATP production in mitochondria through the entry of acetyl-CoA into the Krebs cycle. Fatty acids are oxidized inside the mitochondrial matrix but the fatty acids to be oxidized come from the cytosol. Fatty acids are activated in the cytosol by esterification with Coenzyme A (CoA) to form acyl-CoA (RCO-CoA, where R is the fatty acid acyl group). Activated medium-chain fatty acids (C8 and C10) freely diffuse into mitochondria to be oxidized but long chain fatty acids must be transported in. The transport of long chain fatty acids into mitochondria for oxidation is accomplished by the carnitine palmitoyltransferase system (CPTI and CPTII). CPTI exchanges carnitine for the CoA attached to long chain fatty acids to form a fatty acid-carnitine conjugate (RCO-carnitine). The fatty acid-carnitine is transported into the matrix by a transporter protein in the inner mitochondrial membrane. Once the fatty acid-carnitine is inside the matrix, CPTII exchanges CoA for carnitine to produce fatty acid-CoA once again, ready to enter fatty acid oxidation in the matrix to produce energy. The free carnitine is transported back out to renew the cytoplasmic pool of carnitine and allow the transfer process to continue. (This definition may be outdated - see the DesignNote.)
Any substance that inhibits mitogen-activated protein kinase (MAPK), an enzyme that catalyzes the addition of a phosphate group to a protein in the cell proliferation signaling pathway in response to external stimuli. Inhibition of mitogen-activated protein kinase can result in the inhibition of cell proliferation.
A morphologic finding indicating the presence of a cellular infiltrate with a mixed population of cells in a tissue sample.
A rare primary neoplasm of the uterine corpus characterized by the presence of endometrial stromal and smooth muscle components.
An invasive breast carcinoma characterized by the presence of a mesenchymal cellular component. The mesenchymal cellular component ranges from cartilaginous and osseous, to purely sarcomatous.
A squamous cell carcinoma that arises from the penis and is characterized by a mixture of morphologic patterns (e.g., high grade squamous cell carcinoma and verrucous carcinoma or warty-basaloid carcinoma).
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activites of daily living.
Any subcellular process that results in a specific change in the primary sequence of a biological macromolecule.
A murine monoclonal antibody directed against CD20, a cross-membrane ion channel phosphoprotein expressed by B cells, with potential antineoplastic activity. MOAB 1F5 binds to CD20, thereby directly inhibiting B-cell proliferation and differentiation. When cross-linked by secondary anti-mouse antibodies or Fc receptor-bearing cells, MOAB 1F5 may induce activation of B-cell protein tyrosine kinases, increases in B-cell intracellular calcium ion concentrations, and B-cell caspase activation, resulting in apoptosis of B cells expressing CD20. (NCI04)
A monoclonal immunoglobulin G 1 (IgG1) antibody to murine leukemia virus (MuLV) 1.4. (NCI04)
A nonspecific monoclonal antibody Fab fragment for murine leukemia virus (MuLV) 1.4. Monoclonal antibody 1.4 F(ab) has been used as a control in tests of specific monoclonal antibodies to cancers such as melanoma. (NCI04)
A murine monoclonal antibody that recognizes CD7 (previously known as 3A1), a cell surface antigen expressed by most normal mature peripheral T cells and T cell acute lymphoblastic leukemias. Monoclonal antibody 3A1 is used to diagnose and classify T cell malignancies. This agent can also be conjugated to toxins for potential use in cancer immunotherapy. (NCI04)
A mouse monoclonal antibody (MoAb) with proteoglycan antigen detection and binding activity. Hybridomas of SP2/0 mouse myeloma cells and mouse spleen cells are immunized with cultured human melanoma cells, and subsequently one of the hybridomas secreted MoAb 48.7. MoAb 48.7 is used for detection and binding to the proteoglycan antigen expressed on the cell surface of melanoma cells.
A Fab fragment of the mouse monoclonal antibody (MoAb) 48.7. MoAb 48.7 Fab (fragment antigen binding) recognizes proteoglycan antigen expressed on the cell surface of melanoma cells. The Fab fragments are obtained through papain digestion in the presence of cysteine. The advantage of using MoAb 48.7 Fab fragments over whole antibodies is that they have reduced immunogenicity, better penetration of tissues, rapid clearance from the body and that they do not induce precipitation.
A murine IgM monoclonal antibody against Fas antigen with antineoplastic property. Fas antigen is a member of tumor necrosis factor family that mediates antibody-triggered apoptosis. Upon binds to Fas, monoclonal antibody 7C11 (MoAb 7C11) induces apoptosis in Fas-expressing cells.
A murine IgG2 monoclonal antibody (MoAb) 81C6 raised against the extracellular matrix antigen tenascin (hexabrachion), up-regulated in gliomas and other cancers. Conjugated MoAb 81C6 may be used in diagnosis or treatment of cancers that over-express tenascin.
A mouse monoclonal antibody (MoAb) with binding specificity for the human melanoma-associated cell surface marker p97. Hybridomas of mouse myeloma cells and mouse spleen cells immunized with human melanoma cell were produced, of which one secreted MoAb 8.2. MoAb 8.2 is a monoclonal IgG1 antibody that recognizes an epitope near the amino-terminal portion of p97. This agent is used for detection and binding to p97 antigen expressed on the cell surface of melanoma cells.
A monovalent Fab fragment of the mouse monoclonal antibody (MoAb) 8.2 raised against human melanoma-associated cell surface marker p97. MoAb 8.2 Fab fragments are obtained through papain digestion in the presence of cysteine. The advantage of using 8.2 Fab fragments over whole antibodies is that they have reduced immunogenicity, better penetration of tissues, rapid clearance from the body and that they do not induce precipitation.
A mouse monoclonal antibody (MoAb) with binding specificity for the human melanoma-associated cell surface marker p97. Hybridomas of mouse myeloma cells and mouse spleen cells immunized with human melanoma cell were produced, of which one secreted MoAb 96.5. MoAb 96.5 is a monoclonal IgG2a antibody that recognizes an epitope near the amino-terminal portion of p97. This agent is used for detection and binding to p97 antigen expressed on the cell surface of melanoma cells.
A monoclonal antibody directed against the neurohormone bombesin that is conjugated to diethylenetriaminepenta-acetic acid (DPTA), a bifunctional chelating agent that allows the antibody to be labeled with a metal species such as radioactive indium. Levels of bombesin, also known as gastrin releasing peptide (GRP), are elevated in lung and thyroid cancers, where the substance acts as an autocrine growth factor. (NCI04)
A monoclonal antibody directed against the neurohormone bombesin that is conjugated to isothiocyanobenzyl diethylenetriaminepentaacetic acid (ITC-D), a bifunctional chelating agent that allows the antibody to be labeled with a metal species. Levels of the neurohormone bombesin, also known as gastrin releasing peptide (GRP), are elevated in lung and thyroid cancers, where the substance acts as an autocrine growth factor. (NCI04)
A murine and humanized monoclonal antibody that targets epitopes of epithelial glycoprotein mucin (MUC-1) on breast cancer surfaces. (NCI)
A monoclonal antibody directed against carcinoembryonic antigen (CEA) which is expressed by most gastrointestinal carcinomas and by some breast, lung and ovarian carcinomas. (NCI04)
A murine IgG2 monoclonal antibody against the tumor-associated antigen 17-1A. Administration of monoclonal antibody CO17-1A (Mab C017-1A) elicits an antibody-dependent cell-mediated cytotoxicity. In addition, Mab C017-1A has preclinically acted as an immunogen for development of anti-idiotypic antibody BR3E4. (NCI)
A recombinant immunoglobulin antibody directed against the tumor-associated antigen carcinoembryonic antigen (CEA). CEA is a cell surface glycoprotein expressed at high levels in embryonic and fetal digestive epithelial tissue, breast carcinoma, and squamous cell carcinoma of the head and neck. Except for some reactivity to skin and gastric and colon mucosa, monoclonal antibody COL-1COL-1 does not appear to react with normal tissues. (NCI04)
A recombinant immunoglobulin antibody directed against the tumor-associated carcinoembryonic antigen (CEA). CEA is a cell surface glycoprotein expressed at high levels in embryonic and fetal digestive epithelial tissue, breast carcinoma, and squamous cell carcinoma of the head and neck. Except for some reactivity to skin and gastric and colon mucosa, monoclonal antibody COL-6 does not appear to react with normal tissues.
A human IgG2kappa monoclonal antibody specific for the epidermal growth factor receptor (EGFR). Monoclonal antibody E7.6.3 binds to the EGFR, blocking the binding of epidermal growth factor and transforming growth factor alpha to EGFR-expressing cancer cells and ultimately inhibiting EGFR-dependent cell activation and proliferation. (NCI)
An immunotoxin consisting of the murine anti-CD19 monoclonal antibody HD37 conjugated to a deglycosylated ricin A chain (dgA) via the linking molecule N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene (SMPT). The HD37 component binds to CD19, a B-cell restricted antigen, thereby targeting the delivery of the cytotoxic ricin A chain to B-cells. The ricin A chain component binds to B-cells and disrupts ribosomal activity and protein synthesis and induces cell cycle arrest. (NCI04)
An anti-carcinoembryonic antigen (anti-CEA) murine monoclonal immunoglobulin G (IgG) with potential antineoplastic activity. CEA is overexpressed in several cancer cell types, including gastrointestinal, breast, and non-small cell lung cancers. MOAB IMMU-14 can be conjugated with a radioactive element for use in radioimmunotherapy (RIT), a regimen that uses a tumor-specific monoclonal antibody to deliver targeted radiation to cancer cells. (NCI04)
A recombinant murine monoclonal antibody directed against a human class II molecule variant found on the surfaces of normal and neoplastic human B cells. Monoclonal antibody LYM-2 may induce cell-mediated lysis of neoplastic human B cells. (NCI04)
A chimeric murine-human anti-CD4 monoclonal antibody that down regulates T-helper-inducer function. Clinical Trails: Multiple Sclerosis.
A synthetic immunotoxin consisting of the murine monoclonal antibody N901 conjugated with toxin-blocked ricin (BR). Monoclonal antibody N901-BR binds to CD56, a neural cell adhesion molecule (NCAM) that is expressed by tumor cells of neuroectodermal origin (including small cell lung cancer (SCLC) and neuroblastoma), and by normal cells (including neuroendocrine cells, cardiac muscle cells, and cells in peripheral nerve tissue). (NCI04)
A mouse monoclonal IgG3 antibody that reacts with the cytoplasm and cell surface of colonic adenocarcinoma and shows restricted normal tissue reactivity. NR-CO 04 has been suggested to mediate antibody-dependent cellular cytotoxicity (ADCC).
A murine monoclonal antibody directed against the human epidermal growth factor receptor (EGFR). Monoclonal antibody RG 83852 binds to the EGFR, inhibiting the high-affinity binding of epidermal growth factor (EGF) and receptor activation. Overexpression of EGFR, a tyrosine kinase, and its upregulated activity have been implicated in the pathogeneses of several malignancies. (NCI04)
A teratoma that arises from the testis. It is composed exclusively of one of the following tissue types endoderm, ectoderm, or mesoderm.
A chromosomal abnormality consisting of the absence of a copy (homolog) of chromosome 13.
A chromosomal abnormality consisting of the absence of one of the copies of chromosome 17.
A cytogenetic aneuploidy abnormality that refers to the presence of one chromosome 5 only. It is associated with the development of refractory anemia with excess blasts, refractory anemia with multilineage dysplasia, and refractory anemia with multilineage dysplasia and ringed sideroblasts.
A chromosomal abnormality consisting of the absence of one complete copy of chromosome 6 in somatic cells.
A chromosomal abnormality consisting of the absence of one of the copies of chromosome 7 in somatic cells.
The type of ubiquitin modification determines the functional consequences for the modified protein. Monoubiquitination does not serve as a proteasome targeting signal, but plays other distinct roles. Target proteins are monoubiquitinated on one or more lysine residues, which serve as a signal for intracellular sorting as well as endocytosis of cell-surface proteins. Monoubiquitination of cell-surface receptors serves as a signal to target them to lysosome, where they are degraded by lysosomal proteases. (From PMID and NCI)
An organization of mouse disorders based on the body site affected.
A mucinous cystic tumor of the ovary characterized by the presence of one or more well circumscribed solid nodules in the wall of the cysts (mural nodules) that protrude into the lumen. The mural nodules may be benign (sarcoma-like) or malignant. The malignant mural nodules histologically are anaplastic carcinomas, carcinosarcomas, or sarcomas. The clinical course depends on the histology of the mural nodules. The prognosis of mucinous cystic tumors with benign mural nodules is the same as the corresponding types of mucinous cystic tumors without the mural nodules. Mucinous cystic tumors with malignant mural nodules may follow a malignant clinical course.
An intrahepatic cholangiocarcinoma that produces abundant mucin.
A low grade carcinoma of the kidney characterized by the presence of tubules which are separated by mucinous stroma. Often the tubular structures have a spindle cell appearance. Patients are usually asymptomatic and occasionally they may present with hematuria or flank pain.
A primary, low grade carcinoma of the thyroid gland composed of groups of squamoid and mucous cells, surrounded by fibrous tissue. Prominent cystic structures may be present. The clinical course is usually indolent.
Focal or diffuse epithelial hyperplasia in the intestinal mucosa of the mouse.
An intraosseous ameloblastoma that arises from the jaw, usually the mandible. It grows slowly, invades locally, and recurs frequently. It presents with swelling of the jaw.
A cystic lesion that has more than one compartment.
A finding indicating the presence of more than two tumor masses in a single anatomic site or different anatomic sites.
An immunotoxin consisting of a murine monoclonal antibody (MCA) conjugated to the toxin ricin. The monoclonal antibody component binds to cell surface antigens, thereby targeting delivery of cytotoxic ricin to a specific cell type. The ricin component binds to cells and disrupts ribosomal activity and protein synthesis and induces cell cycle arrest. (NCI04)
A murine retrovirus that contains plasmid DNA (cDNA) coding for the B chain of platelet-derived growth factor (PDGFB). Overexpressed in some human brain tumors, PDGFB and PDGF receptors may stimulate tumor development in an autocrine manner. A murine retrovirus containing human PDGFB cDNA may be used to induce brain tumors in animal models of brain tumorigenesis. (NCI04)
A process that involves the non-covalent interaction of acetylcholine with one of the five muscarinic receptors. These interactions play a role in signal transduction, which influences bodily functions including salivation, lacrimation, urination, digestion and defecation.
Synthetic compounds or mixtures with muscle relaxant activity. A muscle relaxant preparation is used to prevent muscle spasms by inhibiting muscle contractions and to relief pain associated with the spasms.
A blistering agent primarily containing sulfur and chlorine groups that alkylates DNA to form DNA crosslinks, causing inhibition of DNA synthesis.
A mustard compound that gets converted to an active mustard alkylating agent at a tumor site, causing DNA cross-linking. These compounds may be used in antibody-directed enzyme prodrug therapy (ADEPT).
Point-mutation products of Ras proto-oncogene are found to associated with a broad spectrum of human carcinomas. Mutation locations are notably at codons 12, 13, and 61. Codon 12 mutations form more than 90% of all Ras mutations in human cancers. Degraded Ras peptides have been shown to stimulate immunogenic response. Various forms of mutated Ras peptides-adjuvant are used as vaccine along with cytokines that could potentially enhance the body's immunological response in many neoplastic conditions. (NCI04)
A vaccine consisting of myeloma-specific immunoglobulin conjugated to keyhole limpet hemocyanin (KLH), an immune stimulant, with potential antineoplastic activity. Vaccination with myeloma Ig Id-KLH conjugate vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against myeloma cells, resulting in decreased tumor growth. (NCI04)
A multifocal neoplastic process characterized by the proliferation of spindle to cuboidal myoepithelial cells within and/or around small breast ducts.
The phosphorylation of myosin affects its role in smooth muscle contraction, platelet formation, and possibly other processes. Phosphorylation by myosin light chain kinase (MLCK) increases myosin activity and dephosphorylation by myosin phosphatase decreases myosin activity. CPI, a factor that binds to and inhibits myosin phosphatase, is a target of phosphorylation by PKC and PKN. The inhibitory activity of CPI is regulated by its own phosphorylation state; when CPI is phosphorylated, its inhibitory activity is increased. The activation of signal transduction cascades such as GPCR pathways can lead to activation of PKC, phosphorylation of CPI, inhibition of myosin phosphatase, increased myosin phosphorylation, and increased smooth muscle contraction or platelet release. The action of histamine in vasoconstriction, for example, may be mediated by activation of PKC through the histamine receptor, resulting in phosphorylation of CPI-17, increased inhibition of myosin phosphatase, and increased smooth muscle contraction. (This definition may be outdated - see the DesignNote.)
N-Myristoylation is the covalent attachment of myristic acid, a saturated 14-carbon fatty acid inserted in the cytoplasmic leaflet of the lipid bilayer, by an amide linkage to the amino-terminal glycine residue of a protein in order to increase the hydrophobicity of some membrane proteins or to promote membrane localization of some cytoplasmic proteins.
A change in the structure of the NRAS gene.
A synthetic peptide vaccine derived from the melanoma antigen NA17. Dendritic cells (DC) harvested from a cancer patient may be exposed to or pulsed with the NA17 peptide (VLPDVFIRCV). Autologous vaccination with these altered dendritic cells may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for NA17, resulting in decreased tumor growth. (NCI04)
The role of Hemophilus influenzae in ear infections and chronic obstructive pulmonary disease includes the induction of an inflammatory response through activation of the transcription factor NF-kB. In addition to activation of inflammatory cytokine genes like IL-1 and TNF, H. influenzae activates TLR2 expression and genes involved in mucus production. Hemophilus influenzae activates NF-kB by multiple mechanisms, starting with activation of the Toll-like receptor 2 (TLR2) by the p16 protein in the H. influenzae outer membrane. TLR2 plays a key role in innate immune responses and is expressed in high levels in lymphoid cells as well as low levels in epithelial cells. The role of TLR2 was supported by blocking NF-kB activation with a dominant negative TLR2 and increasing it with transfection of a normal TLR2 gene. TLR2 in turn activates TAK1, which activates two divergent signaling pathways. One of these pathways leads to IkB kinase activation, IkB phosphorylation, and degradation, releasing the NF-kB heterodimer to translocate into the nucleus and activate transcription of target genes. In the alternate pathway, TAK1 also activates NF-kB through a Map kinase pathway, activating p38 and NF-kB in a nuclear translocation independent manner. Investigation of the mechanisms of H. influenzae signaling involved in NF-kB activation may provide the information needed to develop better treatments for inflammatory conditions caused by this pathogen. Other pathways modulate the role of NF-kB in H. influenzae pathogenesis. Glucocorticoids, widely used as anti-inflammatory drugs, increase TLR2 activation by H. influenzae through the NIK/I-kB kinase pathway, while they repress the p38 dependent activation of NF-kB. The repression of the p38 pathway by glucocorticoids occurs through activation of the MAP kinase phosphatase-1 (MKP-1) which dephosphorylates and deactivates p38. Another aspect of the inflammatory response to H. influenzae infection is the production of excessive mucus, contributing to the overall symptoms of infection. NF-kB activation of the Muc2 gene contributes to mucus overproduction, in addition to H. influenzae activation of the TGF-beta receptor, activating SMAD transcription factors SMAD3 and SMAD4. Understanding mechanisms that modify H. influenzae signaling will contribute to further understanding the pathogenesis and treatment of ear infections and chronic obstructive pulmonary disease. (This definition may be outdated - see the DesignNote.)
A finding of normality following an examination or investigation looking for the presence of a microorganism, disease, or condition.
Agents administered before, with, or after cancer therapy to reduce or prevent damage or toxicity to the kidney. (NCI)
Nerve growth factor (NGF) is one of a family of neurotrophins that induce the survival and proliferation of neurons. In cell culture NGF induces the formation of neurite projections and in vivo may stimulate the innervation of tissues. NGF plays a role in the repair, regeneration, and protection of neurons, and as such could serve as a therapeutic agent in neurodegenerative conditions such as Alzheimer's disease. One potential method of NGF application would be through gene therapy or through implantation of cells that have been genetically modified ex vivo. NGF has also been suggested to play a role in other physiological systems and tissues such as the immune system. NGF has two receptors, TrkA and the p75(NTR). NGF may signal its neuroprotective actions through the tyrosine kinase TrkA receptor and trigger apoptosis in some cells through the p75 receptor. High-affinity binding of NGF requires both TrkA and p75(NTR). Binding of NGF to the TrkA receptor causes activation of the receptor tyrosine kinase and downstream signaling cascades. One of the downstream signaling pathways of NGF activates phospholipase C, releasing DAG and IP3 and activating associated downstream pathways such as protein kinase C. Another NGF-activated pathway is the ras-mediated activation of the map kinase pathway. This pathway is initiated through recruitment and activation of Shc, which leads to ras activation through Grb-2 and Sos-1. The Map kinase cascade includes raf, Mek and Erk. The downstream effectors of the ras pathway include activation of fos and jun to form AP-1, activating genes through this transcription factor. Other transcription factors involved in NGF responses include Egr and CREB. The Egr family of transcription factors, as well as the Mek/Erk pathway, contribute to NGF-induced neurite formation. The CREB family of transcription factors are involved in NGF-induced survival of sympathetic neurons. Further understanding of NGF signaling may be applied to the modulation of NGF responses in neurodegenerative conditions. (This definition may be outdated - see the DesignNote.)
A process that involves the binding of any member of the group of pituitary hormones, including growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone and prolactin, to their respective receptors. These interactions are essential for glandular development and homeostasis.
A non-neoplastic trophoblastic disorder characterized by the presence of remnants of intermediate trophoblasts in the uterine cavity from a previous pregnancy.
Plasminogen Activator Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction with heterogeneous group of widely expressed lysosomal and secreted serine proteases having fibrin-binding activity that convert plasminogen to fibrinolytic plasmin. Inhibited by PAI-1, encoded by the PLAT Gene (Peptidase S1 Family), and cleaved by plasmin, tissue kallikrein, or factor XA to disulfide-linked A/B chains, tissue-type plasminogen activator plays a role in cell migration and tissue remodeling.
Eph kinases are a family of receptor tyrosine kinases with an extracellular domain that binds their ligand, the ephrins, and an intracellular kinase domain. The ephrins are also expressed on the cell surface, so that interaction between Eph kinases and ephrins occurs at the interface between neighboring cells. Binding of ephrins to Eph kinases stimulates signaling in both directions across the interface between cells, in both the receptor expressing and the ligand expressing cells. Eph kinases and ephrins are involved in several biological processes, and their role in neuronal development has been extensively examined. Both Eph kinases (EphA4 and EphB1) and ephrins (ephrinB1) are expressed on platelets, suggesting that activation of eph kinases by ephrins may play a role in clotting when platelets are brought into close proximity in the developing clot. Platelet activation progresses in stages with an early stage that is stimulated by soluble factors like ADP acting through GPCRs and is reversible and later stages with stronger interaction between platelets that may require interaction between Eph kinases and ephrins. One of the molecular targets of signaling by Eph kinases and ephrins is the actin cytoskeleton, which also plays a role in platelet activation. Clustering Eph kinases or ephrins in platelets stimulated cytoskeletal changes as well as other markers of platelet activation during clotting such as secretion of alpha-granules to release clotting factors. Clustering ephrins together activated Rap1b, a ras gene family member that may regulate integrins. Platelet activation caused Eph kinases to bind to src family members Fyn and Lyn and also with the cell adhesion molecule L1. Failure of the ephrins/Eph kinase pathway to function normally in platelets may result in loosely associated platelets and improper clot formation. Eph kinases and ephrins are also expressed on the vascular wall by endothelial cells, suggesting that signaling by these proteins may also play a role in the interaction of platelets with the vascular wall and clot formation in the vasculature. (This definition may be outdated - see the DesignNote.)
The amyloid-beta peptide (Ab), a proteolytic fragment of amyloid precursor protein (APP), is the major component of senile plaques, the hallmark of Alzheimer's disease. Platelets contain both APP and Ab and probably contribute greater than 90% of circulating APP. The soluble APP is the major inhibitor of coagulation factors IXa and XIa, and platelet aggregation. Agonists such as ADP, thrombin, epinephrine and collagen activate the release of APP and plasminogen activator inhibitor I (an important regulator of coagulation) from platelet storage granules. These important molecules released from platelets are key regulators of hemostasis, the physiologic arrest of hemorrhage at site of vascular leakage. (This definition may be outdated - see the DesignNote.)
A rare, aggressive, high grade invasive ductal carcinoma, not otherwise specified. It is characterized by the presence of pleomorphic and bizarre malignant cells that constitute more than 50 percent of the malignant cellular infiltrate.
A cancer vaccine consisting of Her2/neu peptides incorporated into microspheres of poly (lactide-co-glycolide) (PLGA), a biodegradable polymer. Poly microsphere encapsulated HER2/neu oral vaccine has been investigated for use in immunotherapy for tumors positive for HER-2/neu, a tumor associated antigen that is overexpressed in various cancers, including breast and ovarian cancer. (NCI04)
A compound that inhibits the synthesis of the naturally occurring polyamines, intracellular compounds that bind to DNA and play a critical role in cell division, differentiation and membrane function. These inhibitors affect the activity of enzymes like ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (SAMD) that are involved in the biosynthesis of polyamines. A reduction in intracellular polyamine concentration may lead to a decreased cell growth.
A class of vaccines consisting of multiple antigens conjugated an immunostimulant, keyhole limpet hemocyanin (KLH), QS21 or gp-100. (NCI)
Polycythemia vera characterized by the proliferation of the erythroid, granulocytic, and megakaryocytic lineages. The peripheral blood shows excess of red blood cells, neutrophilia, and thrombocytosis. The bone marrow is hypercellular for the patient's age.
A rare, malignant germ cell tumor arising from the ovary. It is characterized by the presence of embryoid bodies which resemble early embryos.
A rare malignant germ cell tumor that arises from the testis and is characterized by the presence of embryoid bodies.
A raised, outward growing lesion from the surface epithelium or the lumen of an organ. Representative examples include adenomatous and fibroepithelial polyps.
The condition of having additional copies of a chromosome present in a cell.
The type of ubiquitin modification determines the functional consequences for the modified protein. Polyubiquitination, which involves chains of usually four or more ubiquitins, typically seen on cytoplasmic proteins, serve as an efficient signal for recognition by the proteasome and subsequent protein degradation. (From PMID and NCI)
A vaccine designed to elicit an immune response either to more than one infectious agent or to several different antigenic determinants of a single agent.
A neuroblastoma in which the differentiating neuroblasts constitute less than five-percent of the tumor cells.
An ovarian poorly differentiated Sertoli-Leydig cell tumor. It is characterized by the presence of a heterologous component, usually consisting of cartilage, skeletal muscle, or rhabdomyosarcoma.
A finding of abnormality following an examination or observation confirming something, such as the presence of a disease, condition, or microorganism.
Possible adverse event relationship to study product or procedure is defined when there is less clear temporal association between product or procedure administration and adverse event, and other etiologies of the event are also possible.
A malignant vascular neoplasm arising from the skin of the breast secondary to radiation treatment for breast cancer.
Post-Translational Regulation is controlled biochemical alteration of proteins involving generally reversible covalent modification or irreversible processing to regulate activity, location, or stability.
A process that involves the binding of an ion, usually Ca++, Na+ or Cl-, to a potassium channel. These interactions are involved in potassium ion transport, which establishes the electrochemical potential of the resting membrane.
Any disorder caused by an insufficient amount or availability of potassium, which generally manifests with myalgia, tetany, hypotension, polyuria, and polydipsia.
Acute lymphoblastic leukemia of early B-lineage.
Any alteration in cell state that promotes or renders a cell or cell population more vulnerable or prone to malignant conversion or transformation. (NCI)
A serous epithelial tumor that arises from the peritoneum and histologically resembles the serous borderline tumors/atypical proliferative serous tumors that arise from the ovary.
A glioblastoma that arises de novo. It is more commonly seen in older patients. Mutations in IDH1 or IDH2 genes are not present.
A rare carcinoma that arises from the peritoneum and resembles the malignant surface epithelial-stromal tumors that arise from the ovary. Serous adenocarcinoma is the most common histologic variant. It affects women almost exclusively. The diagnosis of primary peritoneal carcinoma can be made only if both ovaries are not involved by tumor, or, if the ovaries are involved, the tumor is confined to the ovarian surface without invasion of the ovarian stroma and the peritoneal involvement is greater than the ovarian surface involvement.
A rare, serous adenocarcinoma that arises from the lining of the peritoneum. It affects females. The clinical behavior and pathologic characteristics are similar to the serous adenocarcinoma that arises from the ovary.
An urothelial carcinoma that arises from the urothelial lining of the prostatic ducts or the prostatic urethra.
Having received extensive radiation before the present time.
Cancer therapy using ionizing radiation to a limited (< 50%) portion of the body.
Probable adverse event relationship to study product or procedure is defined when there is a clear-cut temporal association between product or procedure administration and adverse event, and a potential alternative etiology of the event is not apparent.
A 16 kD N-terminal fragment of prolactin formed endogenously by cleavage of intact prolactin. Possessing anti-angiogenic properties, prolactin 16-kD fragment inhibits the pro-angiogenic effects of basal fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on endothelial cell proliferation, migration, and capillary organization. This agent also induces caspase-mediated endothelial cell apoptosis and upregulates the expression of plasminogen activator inhibitor-1 (PAI-1); PAI-1 inhibits the activity of urokinase, an enzyme essential to angiogenesis. (NCI04)
A finding indicating the presence of a Schwann cell-rich stromal component in a neoplastic tissue specimen.
A topical emollient ointment, by Rystan Company, containing sodium propionate and chlorophyllin copper complex. Chlorophyllin copper complex deodorizes the skin whereas sodium propionate has antifungal activity.
Prostaglandin Degradation consists of conjugation, transport, and/or oxidation of compounds derived primarily from arachidonic acid (cyclooxygenase pathway) (prostaglandins) having potent regulatory effects on the activity of cells involved in host defense and inflammation.
A process that involves the binding of a prostaglandin to a prostaglandin receptor. These interactions are involved in regulation of various functions including the contraction and relaxation of smooth muscle tissue, aggregation and disaggregation of platelets, and inflammation.
An invasive prostate adenocarcinoma characterized by the focal presence of malignant cells that exhibit neuroendocrine differentiation.
An invasive prostate carcinoma composed of prostatic basal cells.
A prostate ductal adenocarcinoma characterized by the presence of neoplastic large back-to-back glands with slit-like lumens.
A prostate ductal adenocarcinoma characterized by the presence of a papillary growth pattern.
A prostate ductal adenocarcinoma characterized by the presence of cribriform and/or papillary patterns and areas of solid nests of malignant cells.
A neoplastic lesion that arises from the prostate gland stroma. Morphologic characteristics include hypercellular stroma with scattered atypical cells, prominent overgrowth of the prostatic stroma, or changes resembling benign phyllodes tumor. The majority of cases do not have an aggressive clinical course. A minority of cases however, may progress to stromal sarcoma.
An urothelial carcinoma that arises from the urothelial lining of the prostatic ducts.
An urothelial carcinoma that arises from the urothelial lining of the prostatic urethra.
Proteasome Binding involves temporary non-covalent interaction through intermolecular physical forces of attraction with multicatalytic macromolecular cellular structures in the cytosol and nucleus with multiple proteolytic activities involved in ATP-dependent ubiquitinated protein degradation and antigen processing.
Proteasome Inhibition involves interference with, or restraint of, the activities of macromolecular multicatalytic cellular structures in the cytosol and nucleus with multiple proteolytic activities involved in ATP-dependent ubiquitinated protein degradation and antigen processing.
Protein-Carbohydrate Interaction is a molecular interaction between protein and carbohydrate molecules.
Protein export is the active transport of proteins from the cytoplasm to the exterior of the cell, or to the periplasmic compartment in Gram-negative bacteria. The sec dependent pathway is the general protein export system that transports newly synthesized proteins into or across the cell membrane. The translocation channel is formed from a conserved trimeric membrane protein complex, called the Sec61/SecY complex. The twin-arginine translocation (Tat) pathway is another protein transport system that transports folded proteins in bacteria, archaea, and chloroplasts. Many Tat systems comprise three functionally different membrane proteins, TatA, TatB, and TatC, but TatA and TatE seem to have overlapping functions, with TatA having by far the more important role.
Nuclear pore complexes (NPCs) are large proteinaceous assemblies that provide the only known portals for exchanging macromolecules between the nucleus and cytoplasm. This includes the movement of small molecules and the selective, facilitated transport of large proteins and RNAs. Faithful, continuous NPC assembly is key for maintaining normal physiological function and is closely tied to proper cell division. One of the unexpected developments during the past decade was the realization that the NPC itself probably does not function primarily as a gating mechanism or by directly transporting cargo macromolecules between the nuclear and cytoplasmic compartments. Instead, nuclear trafficking relies on a range of soluble components. Transport factors bind their cargo in one compartment and then move through the NPCs to the other compartment, where the cargo is released. The transport factor then recycles back through the NPC to participate in another round of transport. In many instances, this process is orchestrated by the Ras-superfamily GTPase Ran. Bischoff et al. describe in detail how the nucleotide state of Ran is controlled by its nuclear guanine-nucleotide-exchange factor (RCC1) and cytoplasmic GTPase-activating protein (RanGAP). The nucleotide state of Ran is crucial to defining the interactions between transport factors, their cargoes and nucleoporins, and is fundamental to the sorting mechanism that defines the directionality of transport. (This definition may be outdated - see the DesignNote.)
G-protein coupled receptors (GPCRs) comprise one of the largest gene families of signaling proteins. Residing in the plasma membrane with seven transmembrane domains, GPCRs respond to extracellular stimuli that include catecholamine neurotransmitters, neuropeptides, larger protein hormones, lipids, nucleotides and other biological molecules. When a GPCR binds its extracellular ligand, it interacts with a G-protein to transduce a signal across the membrane into the cellular interior. G-proteins are a heterotrimeric complex containing a Ga subunit with GTPase activity, as well as b and g subunits. Ga can exist in an active state and an inactive state. Ga in the off state has GDP bound and does not activate downstream signaling molecules. When a GPCR is activated by ligand, it stimulates Ga subunits to bind GTP instead of GDP and become active, dissociating from the receptor and from the b/g subunits to activate downstream signaling factors like the enzyme adenylyl cyclase that synthesizes cyclic-AMP (cAMP) from ATP. Ga turns itself back off again with its intrinsic GTPase activity, hydrolyzing GTP to GDP to become inactive. Activated G proteins interact with downstream signaling factors to alter the production of second messenger signaling molecules like inositolphosphates, calcium and cAMP. GPCRs that activate the Gi class of Ga subunits inhibit cAMP production and GPCRs that activate the Gs class of Ga subunits activate cAMP production. cAMP in turn activates the cAMP-dependent protein kinase, protein kinase A (PKA). PKA is a tetramer composed of catalytic subunits and regulatory subunits that repress the catalytic units when they are bound together. The regulatory subunits bind cAMP when it is present and release the catalytic units, releasing their inhibition of the catalytic subunits as well. The catalytic subunits of PKA when they are released and active phosphorylate target substrate proteins on serine and threonine residues, altering the activity of the modified protein and creating a cellular response to the extracellular stimulus acting on the GPCR. The PKA activation pathway is an example of a signal transduction cascade, in which tying several signaling events together amplifies the original signal in the cell. For each GPCR molecule that is activated, many G-proteins can be activated, and each active G protein can synthesize many cAMP molecules, continuing the cascade to PKA and further downstream. One of the roles of PKA that was first studied was the regulation of glycogen metabolism. When epinephrine binds to its receptor in liver, it activates cAMP production and PKA activation. One substrate of PKA is phosphorylase kinase, which is activated by phosphorylation and is part of the signaling cascade that mobilizes glycogen into glucose to provide energy that fuels the response to epinephrine. Another substrate of PKA is glycogen synthase, which is turned off by PKA phosphorylation. PKA also participates in many other signaling pathways, integrating the key signaling intermediary cAMP with a wide range of biological responses. (This definition may be outdated - see the DesignNote.)
G-protein coupled receptors (GPCRs) transduce a variety of signals from the extracellular environment across the plasma membrane. One of the common signaling systems utilized by GPCRs activates protein kinase C (PKC), a ubiquitous family of serine/threonine protein kinases. The pathway leading to PKC activation starts with a class of GPCRs that interact with and activate Gq G-proteins when the receptor has agonist ligand bound. GPCRs that act through Gq include some muscarinic acetylcholine receptors, many peptide receptors, and the 5-HT2 serotonin receptors. Activated Gq with GTP bound activates its downstream target phospholipase C (PLC) to hydrolyze the membrane lipid PIP2, producing IP3 and diacylglycerol (DAG). IP3 is water-soluble and diffuses through the cytoplasm to the ER, where it binds to and opens a calcium channel, releasing calcium stores from inside the ER into the cytoplasm. Calcium alters many cellular processes, in part by binding to regulatory proteins such as calmodulin and calcineurin. The interaction of both DAG and calcium with PKC activates its kinase activity and the phosphorylation of many different protein targets alters their activity. The involvement of PKC in cellular proliferation and the cell cycle is indicated by the activity of tumor promoters like phorbol esters as PKC activators. (This definition may be outdated - see the DesignNote.)
Any substance that inhibits protein kinase c (PKC), a serine/threonine protein kinase that catalyzes certain cell protein phosphorylation reactions involved in inflammation, mitogenesis, and cell differentiation.
Protein Kinase Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction and spatial complementarity with members of a family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Protein Kinase Protein Phosphorylation involves covalent linkage of a phosphate group (from a donor compound such as ATP) with a serine, threonine, or tyrosine residue of a Protein Kinase acceptor, often as a mechanism of kinase activity regulation.
A process that involves the binding of a cognate ligand to a transmembrane receptor. These interactions are involved in signaling pathways that influence cellular division, cellular differentiation and morphogenesis.
Any substance that inhibits a protein phosphatase, especially those that inhibit the serine/threonine protein phosphatases 1 and 2A, enzymes that regulate entry of the cell into the cell cycle, mitosis and apoptosis. Inhibition of protein phosphatases 1 and 2A can cause cell cycle arrest and apoptosis.
Protein Phosphorylation Inhibition involves interference with, or restraint of, enzymatic activities involved in covalent transfer of a phosphate group from ATP to a protein via the action of a kinase. The major phosphoryl acceptors in proteins are serine, threonine, and tyrosine. Typically, such post-translational modifications regulate protein function.
Any subcellular or molecular event, process, or condition that produces a divergence from the usual wild-type condition in the primary sequence of a peptide or protein molecule. (NCI)
The scanning translation initiation model suggests that 40S ribosomal subunit preloaded with factors bind to the 5' end of the mRNA near the cap. The 48S subunit moves along the mRNA until it finds the initiation triplet and in complex with tRNA and 60S subunit forms the first peptide bond. Translation control is mostly regulated at the protein initiation step through translation initiation factors such as eIF2 or eIF4. (This definition may be outdated - see the DesignNote.)
Termination of the translation process at a stop codon.
Generally irreversible, Proteolytic Processing involves removal of peptide segments from proteins, usually from the N- or C-terminus and often during polypeptide maturation, to regulate activity, location, or stability.
Proton Pump Interaction consists of temporary non-covalent binding of a molecule through intermolecular physical forces of attraction with a membrane associated enzyme, or complex, involved in ATP-dependent transmembrane transport of protons against a concentration gradient, often in exchange for other cations, resulting directly from the expenditure of energy.
Sonic Hedgehog (Shh) is a secreted protein identified genetically as an important developmental factor. Shh provides a morphogenic signal in the developing CNS, organizing the spatial patterning of cells in the midbrain and inducing proliferation of neuronal precursor cells in the developing cerebellum, neural tube, and retina. Proliferative signaling by Shh is involved in the development of cancer, including specific brain and skin cancers such as basal cell carcinomas. Sonic hedgehog signaling may proceed by more than one mechanism. One signaling pathway is activated by Shh binding to Patched (Ptc-1) which releases inhibition of the GPCR Smoothened, activating the Shh signaling pathway and allowing progression through the G1 phase of the cell cycle. Shh can also affect progression through the G2/M transition. Patched binds to phosphorylated Cyclin B1, one component of the M-phase promoting factor (MPF), along with the kinase Cdc2. The interaction of Cyclin B1 with Patched blocks MPF activity, blocking progression through the G2/M transition. Shh binding leads to degradation of Ptc-1, release of Cyclin B1, and entry of the cyclin B1 into the nucleus. Patched acts as a tumor suppressor by blocking MPF activity. Blockade of the Hedgehog pathway by cyclopamine demonstrated the therapeutic potential of Hedgehog inhibition in the treatment of some cancers. (This definition may be outdated - see the DesignNote.)
A germ cell tumor that arises from the testis and is characterized by the presence of one histologic component. This category includes seminoma, teratoma, embryonal carcinoma, yolk sac tumor, and trophoblastic tumor.
Any substance that inhibits purine nucleoside phosphorylase, an enzyme involved in the purine salvage pathway that metabolizes adenosine into adenine, inosine into hypoxanthine, and guanosine into guanine. Inhibition of purine nucleoside phosphorylase results in accumulation of dGTP and the subsequent failure of DNA synthesis, with its greatest effect in T-cells.
This pathway is a compilation of Pyk2 effort cascades; in specific cell types the receptor and effectors will vary. Binding of a transmembrane receptor triggers the activation of Ca2+ signaling and PKC. The signal is then transmitted to Pyk2 and further to the small G protein Rac1. In turn, Rac1 initiatives the JNK cascade, starting with PAK followed by MEKK1, SEK1, and JNK. JNK activation causes induction of c-Jun gene binding. Pyk2 stimulation has also been shown to activate MKK3 leading to activation of p38. The other major mitogen activated kinase cascade for ERK1/2 is stimulated via RAS, RAF and MEKK1/2. (This definition may be outdated - see the DesignNote.)
Quinone Metabolism consists of various biochemical reactions that convert quinones, conjugated aromatic diketones derived from benzene or multiple ring hydrocarbons, to metabolic derivatives.
Once retinoids are bound by the RAR/RXR heterodimer they became transcriptional activated. As a consequence they are degraded by the proteasome. Phosphorylation in the activation domain one (AF1) and presence of the activation domain 2 (AF2) trigger the ubiquitination of the receptors. Moreover, heterodimerization of RAR and RXR accelerate degradation of the receptors. (This definition may be outdated - see the DesignNote.)
A mutation in the RB1 gene that either inhibits expression of the RB1 protein or results in the translation of an inactive RB1 protein.
A recombinant retroviral virus derived from SR-A strain of Rous sarcoma virus carrying a constitutively active form of the AKT Gene. The viral vector RCAS harbors a Replication Competent ALV Splice acceptor. This recombinant virus was use in animal model to study gliomagenesis.
A recombinant retroviral virus derived from SR-A strain of Rous sarcoma virus carrying a human gene encoding the G12D mutant form of K-Ras. The viral vector, RCAS harbors a Replication Competent ALV Splice acceptor. This recombinant virus was use in animal model to study gliomagenesis.
The rel/NF-kB family of transcription factors regulates the activity of genes involved in the immune response, hematopoiesis, and inflammation. NF-kB is a complex of two proteins, p65 (rel) and p50. NF-kB is held inactive in the cytoplasm by I-kB, until signals initiated by TNF or several other factors lead to the phosphorylation and degradation of I-kB and the subsequent release of NF-kB to bind DNA and activate genes. The activation of transcription by NF-kB requires transcriptional coactivators such as p300 and CBP to interact with the rest of the transcriptional apparatus. These coactivators posses enzyme activity, acting to catalyze the posttranslational acetylation of proteins on lysine groups. Acetylation of histones has been known for some time to occur in transcriptionally active chromatin regions. Histone deacetylase (HDAC) enzymes reverse the acetylation of histones. As with other signals, there an off-switch as well as an on-switch for NF-kB activation. The signal to terminate gene activation by NF-kB involves regulation of NF-kB acetylation. P300 and CBP recruited by NF-kB to the transcriptional complex acetylate RelA. Acetylated NF-kB proteins do not interact with I-kB and so continue stimulating transcription. To turn off NF-kB dependent transcription, the histone deacetylase HDAC3 binds to and deacetylates RelA, which then interacts strongly with I-kB once again and is inactivated. The reformed complex of NF-kB and I-kB is exported from the nucleus to the cytoplasm where it replenishes the pool of inactive NF-kB awaiting the next activation signal. The activity of other proteins may also be regulated by acetylation in a similar manner. (This definition may be outdated - see the DesignNote.)
Any substance that inhibits RNA polymerase, an enzyme that catalyzes the polymerization of an RNA strand from a DNA template.
Any recombination occurring in response to DNA breakage induced by ionizing radiation, and resolved with possible exchange and frequent loss of segments of DNA by either homologous recombination or non-homologous end-joining of broken DNA strands. This process is involved in sustaining viability among cells that are irradiated, and occurs frequently at the expense of long-term genomic stability.
Damage to DNA caused by ionizing radiation. Can cause base change mutations or strand breakage.
A macrocyclic antifungal antibiotic, radicicol oxime derivative that binds and selectively depletes heat shock protein 90 (Hsp90) chaperone, a signaling molecule involved in signal transduction that plays a vital role in tumor cells growth. (NCI)
Compounds comprised of a radioactive agent linked to a pharmacological substance to be used to prevent, diagnose, or treat various diseases, including cancer. (NCI)
A radioimmunoconjugate comprised of a humanized monoclonal antibody with antitumor activity. The monoclonal antibody CC49 is developed from the murine monoclonal antibody B72.3 and is humanized by grafting the hypervariable regions onto the variable light (VL) and variable heavy (VH) frameworks of the monoclonal antibodies LEN and 21/28' CL. The resultant antibody binds the pancarcinoma tumor-associated glycoprotein (TAG)-72 with high affinity. Furthermore, the antibody is commonly radiolabeled resulting in an effective agent for use in radioimmunotherapy for treatment of cancer.
Any substance that inhibits Raf Kinase, an enzyme active in signal transduction in the Ras pathway. Inhibition of Raf kinase may result in reduced cell proliferation and cell death.
Ran is a member of the Ras family of small GTPases. Ran is an important component of many crucial nucleocytoplasmic transport pathways. The cycling of Ran is controlled by the RanGTP-RanGDP gradient established by the Ran Guanine nucleotide exchange Factor (RanGEF) RCC1 and the Ran GTPase-activating Protein (RanGAP). These two proteins combine to create a Ran gradient where RanGDP is predominantly cytoplasmic. RCC1 binds to chromatin and so RanGTP is found associated with DNA. RCC1 dissociated GDP from Ran and allows GTP to be bound. As Ran leaves the nucleus the two Ran binding proteins, RanBP1 and RanBP2 cooperate with RanGAP to induce GTP hydrolysis of Ran. There are several nuclear import factors that use the Ran gradient as part of their translocation mechanism. (This definition may be outdated - see the DesignNote.)
An agent designed to inhibit the signal transduction process by interfering with the action of the ras protein.
A synthetic form of the ras peptide containing a point mutation at position 12 (glycine to aspartic acid) with potential antineoplastic activity. Vaccination with ras peptide Asp may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for this ras mutation, resulting in decreased tumor growth. (NCI04)
A synthetic form of the Ras peptide containing a point mutation at position 12 (glycine to cysteine) with potential antineoplastic activity. Vaccination with this peptide may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for this Ras mutation, resulting in decreased tumor growth. (NCI04)
A synthetic form of the Ras peptide containing a point mutation at position 12 (glycine to valine) with potential antineoplastic activity. Vaccination with this peptide may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for this Ras mutation, resulting in decreased tumor growth. (NCI04)
Ras activates many signaling cascades. Here we illustrate some of the well-characterized cascades in a generic compilation of effector molecules. The effectors mediate Ras stimulation to a diverse set of cellular signals. Many of these signals are interpreted differently depending on the cell type or microenvironment receiving the stimulus. Not all of these effectors are activated in any given cell type. The primary method of activation is to promote the translocation of the molecule to the plasma membrane where additional interactions lead to the activation of the molecule. RalGDS is a Guanine Exchange Factor (GEF) for Ral but also has other independent functions. RalGDS activates RalA/B-related small GTPases. RalBP1 is a GTPase activating protein that leads to the inhibition of the Rac and CDC42 GTPases. Ral can also interact with phospholipase D1 (PLD1) that can also be activated by RhoA. Ras stimulation of the lipid kinase activity of PI3K occurs through an interaction with the p110 catalytic subunit. PI3K phosphorylates the D3 position of phosphatidylinositides. In this example Pip2 is converted to PIP3. PIP3 stimulates the AKT/PKB kinase and several of the Rac-GEFs such as Sos1 AND Vav. AKT activation inhibits apoptosis by inhibiting the actions of Bad, Caspase 9, and AFX. AKT further hinders apoptosis by phosphorylating the IkB repressor of NFkB. Stimulus of Rac causes, among other things, the activation of NFkB. Ras also stimulates the mitogen-activated kinases ERK1/2 via the Raf1 cascade. The Erk kinases translocate to the nucleus where they phosphorylate various transcription factors such as ELK1. (This definition may be outdated - see the DesignNote.)
An intercellular process that involves a cellular receptor binding to a cognate ligand and results in a specific cellular response.
Passage or transfer, as of a disease, by blood transfusion from a donor individual to a recipient. (NCI)
Adult T-cell Leukemia derived factor: Human thioredoxin. A cytokine.
A replication-defective, recombinant adenoviral vector encoding the wild-type human tumor-suppressor protein p53 gene with potential antineoplastic activity. Upon intratumoral administration, rAD-p53 binds to the coxsackie-and-adenovirus receptor (CAR) on tumor cells and enters cells selectively via receptor-mediated endocytosis, which may result in the overexpression of wild-type p53 intracellularly and p53-mediated tumor regression. In addition, this agent may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) immune response against tumor cells, may activate natural killer (NK) cells to exert antitumor 'bystander effects' and may downregulate the expression of various oncogenes. The p53 protein blocks tumor cell cycle progression and directly initiates apoptosis; the p53 gene, a tumor suppressor gene, is deleted or mutated in a significant number of cancers.
A recombinant form of amphiregulin, a member of the heparin-binding epidermal growth factor (EGF) family. Endogenous amphiregulin is an autocrine growth factor, and binds to the EGF receptor. Overexpressed in several cancer cell types, endogenous amphiregulin may contribute to tumor cell proliferation and metastasis. (NCI04)
A 14kD non-glycosylated human derived angiogenesis factor, which has the ability to induce neovascularisation with a unique ribonucleolytic activity. (NCI)
A recombinant form of the endogenous Betacellulin, a member of the Epidermal Growth Factor family that is expressed primarily in the pancreas and induces differentiation of a pancreatic acinar cell line.
A recombinant form of the heparin-binding fibroblast growth factor 5 (FGF-5). FGF-5 may function as a growth factor during embryogenesis and may have a role in wound repair throughout adulthood because of its mitogenic effects on fibroblasts and endothelial cells. Overexpressed in certain tumor cell types, this agent may promote tumor growth and angiogenesis. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous fibroblast growth factor 6 (FGF-6). Because of the mitogenic effects of FGF-6 on fibroblasts and endothelial cells and the stimulatory effects of FGF-6 on muscle stem cell migration, therapeutic FGF-6 has a potential role in wound healing and muscle regeneration. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous fibroblast growth factor 7 (FGF-7). Because it stimulates proliferation and differentiation in parenchymal epithelial cells of differentiated tissues, recombinant FGF-7 may be useful in the treatment of wounds and pathologies associated with dermal adnexa, liver, lungs and the gastrointestinal tract. (NCI04)
A vaccine consisting of a replication-defective recombinant fowlpox virus that encodes for the murine melanoma antigen glycoprotein 100 (mgp100) with potential antineoplastic activity. Vaccination with recombinant fowlpox-mgp100 vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the gp100 antigen, resulting in decreased tumor growth. (NCI04)
A viral vaccine comprised of a recombinant fowlpox vector construct encoding a modified epitope of the melanoma antigen glycoprotein 100 (gp100), ES-2092M(gp100), containing an endoplasmic reticulum signal sequence targeted to the endoplasmic reticulum apparatus. Vaccination with recombinant fowlpox-gp100p209 vaccine may stimulate the host immune system more efficiently to mount a cytotoxic T lymphocyte response against tumor cells expressing the gp100 antigen.
Recombinant form of endogenous Insulin-like Growth Factor II exhibiting mitogenic activity.
Recombinant form of endogenous thymopoietin, a thymic hormone.
A recombinant vaccinia virus encoding carcinoembryonic antigen (CEA). CEA is overexpressed in several cancer cell types, including gastrointestinal, breast, and non-small cell lung cancers. Attenuated vaccinia virus is a highly effective immunizing agent that evokes both humoral and cell-mediated responses. Vaccination with this agent may evoke a cytotoxic immune response to CEA-expressing cells. (NCI04)
An admixture of recombinant vaccinia virus encoding MUC-1 and recombinant vaccinia virus encoding the murine T-cell co-stimulatory molecule B7.1. MUC-1 is a glycosylated mucin that is overexpressed in breast, lung, pancreatic, prostate, stomach, colon, and ovarian carcinomas. Vaccination with MUC-1 in combination with B7.1 may enhance the cytotoxic T cell (CTL) immune response to tumors expressing MUC-1, compared to vaccination with MUC-1 alone. (NCI04)
A recombinant vaccinia virus encoding prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA) with potential use in cancer immunotherapy. (NCI04)
A recombinant vaccinia virus encoding prostate-specific antigen (PSA). Vaccination with recombinant vaccinia-PSA may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for PSA, which may decrease tumor growth. (NCI04)
A recombinant vaccinia virus encoding the melanocyte differentiation antigen tyrosinase-related protein-1 (TRP-1) with potential use in cancer immunotherapy. (NCI04)
A recombinant vaccinia virus encoding a modified peptide of the gp100 melanoma-melanocyte antigen with potential use in cancer immunotherapy. gp100 human antigen is a wild type self-antigen expressed by melanocytes, pigmented retinal cells and most melanomas. gp100p209 is a fragment epitope of gp100 in which the threonine in position 2 is replaced with methionine; this modification may stimulate tumor infiltrating lymphocytes (TIL) more efficiently. (NCI04)
The reemergence of high grade B-cell lymphoma Burkitt-like lymphoma after a period of remission
Reelin is an extracellular protein secreted by neurons. Reeler mice with a defective Reelin gene exhibit neuronal abnormalities in development. Mice that are heterozygous for the Reelin knockout have neuroanatomical and behavioral traits similar to those of schizophrenia patients, suggesting that mice with a deficiency in Reelin may provide a useful model for schizophrenia. Reelin protein may be involved in cognitive function in adults as well as playing a role in the developmental organization of neurons in the cortex. Multiple cell surface receptors transduce Reelin signaling into neurons. One class of Reelin receptor includes the VLDL receptor and the ApoER2. The intracellular adaptor Dab1 binds to the VLDL receptor and ApoER2 receptor through an NPxY motif and is involved in transmission of Reelin signals through these lipoprotein receptors. Mutation of the mDab1 gene in mice creates a phenotype identical to Reeler mice, supporting the role of this cytoplasmic factor in signaling downstream from Reelin. Another class of receptor for Reelin is the cadherin-related neuronal receptors, CNR receptors. Reelin signaling through several different CNR receptors activates the Fyn tyrosine kinases. Reelin stimulates phosphorylation of Dab1 and Dab1 appears to link Reelin signaling with tyrosine kinases. Disruption of the p35 and Cdk5 genes in mice indicates that cdk5 is also involved in the role of Reelin in neuronal development. (This definition may be outdated - see the DesignNote.)
High grade B-cell lymphoma Burkitt-like lymphoma resistant to treatment.
A disease or condition that extends beyond the site and spreads into adjacent tissues and regional lymph nodes.
Nicotinic acetylcholine receptors are essential for neuromuscular signaling and are also expressed in non-neuronal tissues, where their function is less clear. Although nicotinic acetylcholine receptors are primarily known for their action as ligand-gated ion channels transducing action potentials across synapses, they may have other actions. Nicotinic acetylcholine receptors in neurons alter apoptotic signaling, protecting against cell death in some settings, and this action may in some cases be directed through alternative signaling pathways. In neurons the alpha-7 nicotinic receptor activates PI3 kinase through a src-family kinase, activating the anti-apoptotic kinase AKT (See AKT signaling pathway). One pathway involved in AKT signaling involves phosphorylation of the forkhead transcription factor FKHRL1, causing its retention in the cytoplasm associated with 14-3-3, and blocking expression of the apoptotic fas protein. The PI3 kinase/AKT pathway protects a broad range of neurons against apoptotic cell death and may block apoptosis triggered by beta-amyloid fragments that contributes to the progression of Alzheimer's disease. If so, nicotinic agents may prove useful in the treatment of this and other neurodegenerative conditions. There are several proteins that modulate the response of nicotinic acetylcholine receptors, include synapse formation. Prior to synapse formation, nicotinic receptors are randomly dispersed in the post-synaptic membrane. A neuronal protein, agrin, binds to the Musk receptor in the muscle membrane, stimulating clustering of nicotinic receptors and synapse formation. Rapsyn is present at high levels at synapses with nicotinic receptors, bringing them together at high densities and anchoring clustered receptors to the cytoskeleton. Members of the Src family of tyrosine kinases also play a role in clustering caused by Rapsyn, phosphorylating the nicotinic receptors, rapsyn, and other targets. Nicotinic receptors expressed in non-neuronal tissues may also be involved in the response to smoking. In lung epithelial cells, nicotine from cigarette smoke blocks apoptosis by activating the anti-apoptotic kinase AKT, contributing perhaps to carcinogenesis and resistance to chemotherapy. Activation of nicotinic acetylcholine receptors in dermal fibroblasts may contribute to the altered wound healing and skin elasticity related to smoking. Activation of keratinocyte nicotinic receptors may also alter the properties of skin. (This definition may be outdated - see the DesignNote.)
Cholesterol is essential for life but a key in the development of heart disease. Cholesterol homeostasis is achieved through regulation of cholesterol uptake, cholesterol biosynthesis, cholesterol conversion to bile acids and excretion of bile acids. Inhibition of cholesterol biosynthesis up regulates LDLR expression and is the mechanism of action of many drugs used to lower plasma LDL to reduce coronary heart disease. Many aspects of cholesterol homeostasis are regulated by the nuclear receptors FXR and LXR, both nuclear receptor transcription factors that form heterodimers with the retinoic acid RXR receptors and that are activated by cholesterol metabolites. One of the primary tissues in cholesterol metabolism is the liver, a key site of cholesterol biosynthesis and where cholesterol low-density lipoprotein (LDL) is taken up from the plasma by the LDL-receptor. When cholesterol accumulates in liver cells, some of the cholesterol is oxidized to create oxysterols. Oxysterols activate LXR through LXR/RXR heterodimers to activate genes such as the CYP7A1 enzyme that catalyzes the rate-limiting step in bile acid biosynthesis and a major route for the elimination of cholesterol. Animals lacking the CYP7A1 enzyme accumulate cholesterol in the liver. In the intestine LXR activates the ABC-1 gene, a transporter that actively transports cholesterol out of cells to clear it from the body. Activation of ABC-1 expression by LXR in macrophages in atherosclerotic plaques appears to be another mechanism by which LXR plays a role in heart disease. The FXR receptor is activated by bile acids. In the liver, activation of FXR-RXR heterodimers by bile acids results in the feedback inhibition of CYP7A expression and reduced biosynthesis of bile acids. In the intestine, FXR activates expression of I-BABP, a protein that increases the transport of bile acids back to the liver from the intestine, reducing their excretion. Drugs targeting the FXR and LXR receptors could play an important role in modulating cholesterol homeostasis and heart disease in the future. (This definition may be outdated - see the DesignNote.)
Biochemical and cellular mechanisms involved in Regulation of Proteolysis ensure that hydrolysis of one or more peptide bonds within target proteins by proteolytic enzymes occur at the correct time and location.
A renal cell carcinoma with papillary architecture comprised of clear cells. It is characterized by the inv(X)(p11;q12) resulting in fusion of the NONO (p54nrb) and TFE3 genes.
A renal cell carcinoma with papillary architecture comprised of clear cells. It is characterized by the t(X;1)(p11.2;q25) resulting in fusion of the ASPL and TFE3 genes.
A renal cell carcinoma with papillary architecture comprised of clear cells. It is characterized by the t(X;1)(p11.2;p34) resulting in fusion of the PSF and TFE3 genes.
A renal cell carcinoma with papillary architecture comprised of clear cells. It is characterized by the t(X;1)(p11.2;q21) resulting in fusion of the PRCC and TFE3 genes.
A benign neoplasm of the renal pelvis that involves the transitional epithelium projecting above the surrounding epithelial surface and consisting of villous or arborescent outgrowths of fibrovascular stroma.
A Replication Error results from the covalent addition of an incorrect nucleotide subunit, or the lack of addition of a nucleotide subunit, during polymerization of the growing newly synthesized DNA strand during replication. (NCI)
Return to the normal structure and/or function, e.g. the subsidence of a pathologic process, as the subsidence of an inflammatory lesion or new growth.
An adenoma that arises from the rete ovarii. It is composed of elongated tubules. The clinical course is benign.
An exceptionally rare cystadenofibroma that arises from the rete ovarii.
An exceptionally rare cystadenoma that arises from the rete ovarii.
A benign or malignant neoplasm that arises from the rete ovarii which is located in the ovarian hilus. It includes adenoma, cystadenoma, cystadenofibroma, and adenocarcinoma.
A benign epithelial neoplasm arising from the rete testis.
A benign or malignant neoplasm that affects the rete testis. Representative examples include adenoma and adenocarcinoma.
A benign vascular tumor of the retina without any neoplastic characteristics.
Retinoic Acid Binding consists of a biophysical interaction between retinoic acid (ligand) and a biological molecule, such as specific steroid receptor-like transcriptional regulator proteins containing an N-terminal modulating domain, a DNA-binding domain, and a C-terminal ligand-binding domain. The ligand-activated receptor complexes selectively bind as homodimers or heterodimers (with other steroid family receptors) to DNA response elements in target gene promoters, enhance transcriptional activity with coactivators, and mediate tissue growth and differentiation in embryogenesis, organogenesis, limb development, bone growth, and maintenance of normal epithelia.
Peptides built of D-amino acids in the reversed sequence order. These may adopt structures similar to their L-counterparts while being more resistant to proteolytic degradation.
A multinodular intermediate fibroblastic neoplasm arising from the retroperitoneum. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells.
A recombinant retrovirus containing the modified murine retroviral vector MFG-S encoding a chimeric construct, MOv18-gamma. MOv18 is a murine monoclonal antibody developed against epitope of human folate binding protein, which is overexpressed on more than 90% of non-mucinous epithelial ovarian neoplasms. The chimeric construct (MOv18-gamma) encodes the variable region of MOv18 antibody, and the gamma chain of human T-cell receptor. This virion might be used to transduce autologous T lymphocytes, and reintroduced back to the patient after expansion ex vivo to invoke specific immune response against ovarian cancer cells.
Cyclin-dependent kinase inhibitor-2A (CDKN2A) goes by the colloquial designation p16, which is sometimes referred to as p16(INK4). The alpha transcript of CDKN2A has been shown to encode p16(INK4a), a recognized tumor suppressor that induces a G1 cell cycle arrest by inhibiting the phosphorylation of the RB protein by the cyclin-dependent kinases CDK4 and CDK6. The beta transcript of CDKN2A encodes p14(ARF). The predicted 132-amino acid p14(ARF) is shorter than the corresponding mouse protein, p19(ARF), and the 2 proteins share only 50% identity. However, both proteins have the ability to elicit a p53 response, manifest in the increased expression of both CDKN1A and MDM2, and resulting in a distinctive cell cycle arrest in both the G1 and G2/M phases. Two unrelated proteins encoded by the INK4A-ARF locus function in tumor suppression. ARF binds to MDM2 and promotes the rapid degradation of MDM2. This interaction is mediated by the E1-beta-encoded N-terminal domain of ARF and a C-terminal region of MDM2. ARF-promoted MDM2 degradation is associated with MDM2 modification and concurrent p53 stabilization and accumulation. The p19(Arf) tumor suppressor inhibits production of ribosomal RNA, retarding processing of 47/45S and 32S precursors. These effects correlate with but do not strictly depend upon inhibition of rRNA biosynthesis or cell cycle arrest, are not mimicked by p53, and require neither p53 nor Mdm2. Arf mutants lacking conserved amino acid residues 2-14 do not block rRNA synthesis and processing or inhibit cell proliferation. Evolution may have linked a primordial nucleolar Arf function to Mdm2 and p53, creating a more efficient checkpoint-signaling pathway for coordinating ribosomal biogenesis and cell cycle progression. (This definition may be outdated - see the DesignNote.)
Ribosomal Interaction involves temporary non-covalent binding between biomolecules and ribosomes.
Ribosome Assembly Interference involves inhibition or restraint of the formation of ribosomes.
Processes that involve interference with, or restraint of, the activity of ribosomes.
Stage IV NHL means disseminated (multifocal) involvement of one or more extralymphatic sites with or without associated lymph node involvement or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement. (from PDQ)
Stage I NHL means involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE). (from PDQ)
STATs, Signal Transducers and Activators of Transcription, are transcription factors that are phosphorylated by JAK kinases in response to cytokine activation to dimerize and move into the nucleus to activate transcription of cytokine-responsive genes. There are at least 3 JAK kinases and at least six STATs, with different cytokines inducing different patterns of JAK and STAT activation. Cytokines that activate STAT3 include growth hormone, IL-6 family cytokines, and G-CSF. STAT3, as well as STAT5, induces progression through the cell cycle, prevents apoptosis, and may be associated with cancer development in some cases. STAT3 plays an important role in normal development, particularly hematopoiesis. The importance of STAT3 is underscored by the failure of mice lacking STAT3 to survive embryogenesis. Crosstalk from pathways other than JAK kinases also leads to phosphorylation and activation of STAT3 as indicated by a role of mTOR (mammalian target of rapamycin, or p70 S6 kinase) and mitogen-activated protein kinase (MAP kinase) pathways in STAT3 activation and signaling. (This definition may be outdated - see the DesignNote.)
Stathmin is a ubiquitous, cytosolic 19-kDa protein, that is phosphorylated on up to four sites in response to many regulatory signals within cells. Its molecular characterization indicates a functional organization including an N-terminal regulatory domain that bears the phosphorylation sites linked to a putative alpha-helical binding domain predicted to participate in coiled-coil, protein-protein interactions. In addition to the protein kinases that phosphorylate Stathmin such as CaMK, MAPK, p34cdc2, PKA, a few other proteins have been suggested to interact with stathmin in vivo. One of them was identified as BiP, a member of the hsp70 heat-shock protein family. Another is a previously unidentified, putative serine/threonine kinase, KIS, which might be regulated by stathmin or, more likely, be part of the kinases controlling its phosphorylation state. Finally, proteins CC1 and CC2, predicted to form alpha-helices participating in coiled-coil interacting structures. It has been suggest that the action of antimicrotubule drugs can be affected by stathmin in at least two ways: (a) altered drug binding; and (b) growth arrest at the G2 to M boundary. Mutant p53 breast cancers exhibiting high levels of stathmin may be resistant to antimicrotubule agents. (This definition may be outdated - see the DesignNote.)
An aromatase inhibitor with a steroidal structure. Steroidal aromatase inhibitors work by forming a permanent bond with the enzyme.
A predominantly female hormone derived from cholesterol belonging to the family of Steroid Hormones and is responsible for maintaining the health of reproductive tissues, breast, skin, and brain. By-products of estrogen metabolism are thought to cause breast and prostate cancer.
The A-kinase anchor protein 13 (AKAP13, also known as AKAP-LBC) is one of a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. AKAP13 is a splice variant of the oncogene Lbc. Alternative splicing of the AKAP13 gene results in at least 3 transcript variants encoding different isoforms containing a Dbl oncogene homology (DH) domain and a pleckstrin homology (PH) domain. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. These splice variants contain a fragment that was originally identified as Ht31 (See Carr et al 1991) which acts as a scaffolding protein to regulate the Rho signaling pathway and as protein kinase A-anchoring protein creating a coordination of these two signaling pathways. Diviani et al. found that in HEK293 cells LPA induced stimulation preferentially activates AKAP13 via G-alpha12. As yet targets for the anchored PKA have not been identified. AKAP13 and Rho do not appear to be phosphorylated by PKA. Diviani et al also found that the Lbc oncogene and protooncogene splice variant show higher activation and stress fiber localization. This appears to be a result of the presence of N terminal inhibitory sequences. A similar model of regulation has been proposed for Dbl and Vav. (This definition may be outdated - see the DesignNote.)
Any intracellular process that involves a chemical or mechanical stimulus and results in a cellular response that is specific to the stress.
Any change in the structure of one or more chromosomes.
An adenocarcinoma of the colon that has invaded into the submucosa.
Substrate Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction and spatial complementarity between biologically-active molecules and their target molecule or between a biological molecule and an underlaying surface.
Like ubiquitin, SUMO (small ubiquitin-related modifier) proteins are small protein tags that are conjugated to proteins to modify their function. The ubiquitin system tags proteins for degradation by the proteasome but SUMO conjugation has a range of other functions, stabilizing some proteins and altering their subcellular localization. Sumoylation may also influence ubiquitination and protein stability indirectly. Three different SUMO proteins are conjugated to proteins, SUMO-1, SUMO-2 and SUMO-3. The SUMO-2 and SUMO-3 genes are closely related, with 86% sequence identity while SUMO-1 is less closely related with about 50% sequence identity with SUMO-2 and SUMO-3. These SUMO proteins also have distinct functions, with SUMO-1 conjugated to proteins as a monomer, while SUMO-2 and SUMO-3 are conjugated to proteins as higher molecular weight polymers with SUMO-1 terminating further SUMO addition. SUMO proteins are first activated by adenylation by one enzyme complex (SAE1/SAE2), then transferred to Ubc-9 and finally to the terminal amino group of a lysine side chain in target proteins. The same conjugation system appears to work for all three SUMO proteins. One target of SUMO modification is proteins involved in formation of the PML nuclear bodies, promoting the stability of these structures and perhaps altering their role in transcriptional regulation, cellular proliferation and anti-viral responses. Other targets of SUMO addition include DAXX, p53 and ran-Gap. The transcriptional activation by p53 is increased by SUMO addition. The localization of DAXX to the PML nuclear bodies and the localization of ran-Gap to the nuclear pores are also regulated by SUMO addition. The activity of several transcription factors is altered by sumoylation, including C/EBP proteins, c-Myb, glucocorticoid receptor, androgen receptor, and progesterone receptor. PIAS is a protein that modulates the activity of many different transcription factors perhaps by acting itself as a sumo ligase. Sumoylation of topoisomerase I alters its localization in the nucleus, and histone deacetylase enzymes are targets of this system. Viral proteins are targets of sumoylation, suggesting that infection and anti-viral cellular defenses may be affected by this system. Sumoylation may also alter the stability of proteins with polyglutamine repeats involved in neurodegenerative disorders, adding further to the important and diverse roles of this protein modification system. (This definition may be outdated - see the DesignNote.)
Current data indicates that nuclear pore complex (NPC) RanBP2 (SUMO E3 ligase) protein sumoylates Mdm2 and HDAC proteins during nuclear translocation. A sumoylation-deficient HDAC showed reduced deacetylation activity and suggests that sumoylation may be an important regulatory mechanism for the control of transcriptional repression. (This definition may be outdated - see the DesignNote.)
Covalent attachment of one eukaryotic protein to another is a prominent posttranslational modification and Ubiquitin is the most familiar of the protein modifiers. Recently a new group of ubiquitin-like (Ubl) proteins have come to light. One of the most intriguing of them is SUMO (small ubiquitin-like modifier, 12kDa) also known as Sentrin. SUMO family has been described in vertebrates: SUMO-1 and the closest homologs SUMO-2 and SUMO-3. SUMO have been shown to bind and regulate mammalian SP-RINGs (such as Mdm2, PIAS and PML), RanGAP1, RanBP2, p53, p73, HIPK2, TEL, c-Jun, CtBP, Fas, Daxx, TNFRI, Topo-I, Topo-II, WRN, Sp100, IkB-alpha, Androgen receptor (AR), GLUT1/4, Drosophila Ttk69, Dorsal, CaMK, yeast Septins, and viral CMV-IE1/2, EBV-BZLF1, HPV/BPV-E1. In the case of the transcription co-repressor CtBP, which can be recruited to the target promoter via interaction with a conserved PxDLS motif in the interacting repressor, CtBP SUMOylation profoundly affected its subcellular localization. SUMOylation occurred at a single Lys residue, Lys428, of CtBP1. Mutating Lys428 into Arg (K428R) shifted CtBP1 from the nucleus to the cytoplasm, while it had little effect on its interaction with the PxDLS motif. The K428R mutation also abolished the ability of CtBP1 to repress the E-cadherin promoter activity. Consistent with the known inhibitory effect of nNOS on the nuclear accumulation of CtBP1, PDZ domain of nNOS inhibits the SUMOylation of CtBP1. The current data indicates that SUMOylation can regulate CtBP1-dependent transcriptional repression. (This definition may be outdated - see the DesignNote.)
Carcinoma that is detected in one breast within two months from the diagnosis of carcinoma in the other breast.
A cationic liposomal, tumor-targeting p53 (TP53) gene delivery system with potential anti-tumor activity. Transferrin receptor-targeted liposomal p53 cDNA contains plasmid DNA encoding the tumor suppressor protein p53 packaged in membrane-like liposome capsules that are complexed with anti-transferrin receptor single-chain antibody (TfRscFv). Upon systemic administration, the anti-TfRscFv selectively binds to tumor cells expressing transferrin receptors. The p53 plasmid is delivered into the nucleus and as a result, p53 protein is produced in tumor cells that have altered p53 function. This results in the restoration of normal cell growth control mechanisms as well as normal response mechanisms to DNA damage.
An ozonide of Terpene designed to oxidize tumor cells and control metastasis. (NCI)
For a T cell to be activated by a specific antigen, the T cell receptor must recognize complexes of MHC-1 with the antigen on the surface of an antigen-presenting cell. T cells and the T cell receptor complex do not respond to antigen in solution, but even for the specific antigen they only respond to antigen-MHC-1 complexes on the cell surface. This interaction is necessary for T cell activation, but it is not sufficient. T cell activation also requires a co-stimulatory signal involving interaction of CD28 on the T cell with CD80 or CD86 (B7 family genes) on the antigen-presenting cell. CD28 activates a signal transduction pathway acting through PI-3K, Lck and Grb-2/ITK to provide its co-stimulatory signal for T cell activation. Another means to control T cell activation is by expressing factors that down-regulate T cell activation. Signaling by activated T cell receptors induces expression of CTLA-4, a receptor that opposes T cell activation. CTLA-4 has a higher affinity than CD28 for B7 proteins, terminating T cell activation. ICOS is a protein related to CD28 that is only expressed on activated T cells, and that provides another important co-stimulatory signal. The requirement for co-stimulatory signals provides additional control mechanisms that prevent inappropriate and hazardous T cell activation. (This definition may be outdated - see the DesignNote.)
Vasoactive intestinal peptide (VIP) and the structurally related pituitary adenylate cyclase-activating polypeptide (PACAP), two neuropeptides present in the lymphoid microenvironment, elicit a broad spectrum of biological functions, including the modulation of innate and adaptive immunity. Another important immunoregulatory function of VIP and PACAP is their inhibition effect on AICD in T cells. They inhibit the TCR-stimulated FasL expression and apoptosis of T cell through specific receptors and induction of intracellular cAMP. VIP down-regulate c-Myc synthesis, the NF-AT-dependent Egr2 and Egr3 expression, the NF-AT and NF-kB. (This definition may be outdated - see the DesignNote.)
Mef2 (Myocyte enhancer factor 2) transcription factors play a role in T-Cell calcium induced apoptosis. Several factors regulate Mef2 transcription factors, including Map kinases and histone deacetylase (HDAC) enzymes. (This definition may be outdated - see the DesignNote.)
T-cell large granular lymphocyte leukemia defined by the presence of CD3-positive, CD8-positive, and T-cell receptor alpha-beta-positive cytotoxic T-cells.
An uncommon variant of T-cell large granular lymphocyte leukemia expressing the gamma-delta T-cell receptor. Approximately 60% of these cases are CD8-positive and the remainder are CD4/CD8-negative.
A cancer vaccine consisting of a recombinant vector encoding the tumor-associated carcinoembryonic antigen (CEA) that is contaminated with bovine viral diarrhea virus (BVDV). The carcinoembryonic antigen (CEA) is a prevalent tumor marker expressed by a number of different cancers such as colorectal, breast, lung and ovarian carcinomas; vaccination with vaccinia virus genetically engineered to express CEA may generate antitumoral T-cell responses. BVDV is an RNA pestivirus that may contaminate vaccines due to its presence in fetal calf serum used as a growth supplement in the tissue culture of mammalian cells used in vaccine production. (NCI04)
Any process in which a specific pair of interactions is observed between a T cell and an antigen-presenting cell, where the interactions include those between the T cell receptor and the major histocompatibility complex and those between CD28 and B7 family members. This process is involved in anergy and specification of the immune response to a particular antigen.
Expression of a fusion protein containing the helix-loop-helix domain encoded by the human ETV6 gene and the DNA-binding and transactivation domains encoded by the human RUNX1 gene as a result of a t(12;21)(p13; q22) translocation.
Expression of the ETV6-PDGFRB fusion transcript resulting from the rearrangement of the PDGFRB gene.
An immunotoxin composed of an anti-p80 monoclonal antibody and a toxin moiety, which targets antigen-positive cells and causes cytotoxic activity. (NCI)
A mutation in the TP53 gene that either inhibits the expression of or results in the translation of an inactive cellular tumor antigen p53 protein.
A recombinant peptide consisting of amino acid residues 1 to 9 of the tyrosinase-related protein 1 (TRP1). Expressed by cells of melanocyte origin, TRP1 is an enzyme involved in the process that converts tyrosinase to melanin pigments. Vaccination with TRP1(0RF3):1-9 may stimulate cytotoxic T cell responses to melanoma cells.(NCI04)
A mutation in the TSC1 gene that either inhibits the expression of or results in the translation of an inactive hamartin protein.
A mutation in the TSC2 gene that either inhibits the expression of or results in the translation of an inactive tuberin protein.
As tissues grow they require angiogenesis to occur if they are to be supplied with blood vessels and survive. Factors that inhibit angiogenesis might act as cancer therapeutics by blocking vessel formation in tumors and starving cancer cells. Thrombospondin-1 (TSP-1) is a protein that inhibits angiogenesis and slows tumor growth, apparently by inducing apoptosis of microvascular endothelial cells that line blood vessels. TSP-1 appears to produce this response by activating a signaling pathway that begins with its receptor, CD36, at the cell surface of the microvascular endothelial cell. The non-receptor tyrosine kinase fyn is activated by TSP-1 through CD36, activating the apoptosis inducing proteases such as caspase-3 and p38 protein kinases. p38 is a mitogen-activated kinase that also induces apoptosis in some conditions, perhaps through AP-1 activation and the activation of genes that lead to apoptosis. (This definition may be outdated - see the DesignNote.)
A synthetic peptide vaccine consisting of amino acids 206 through 214 of the melanoma-associated antigen tyrosinase. Vaccination with TYROSINASE_206-214 may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for tyrosinase, resulting in decreased tumor growth. (NCI04)
A synthetic peptide consisting of amino acids 368 through 376 of the melanoma-associated antigen tyrosinase with an amino acid aspartic acid at position 370 to improve immunogenicity. Vaccination with TYROSINASE:368-376(370D) may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for tyrosinase, thereby decreasing tumor growth.
A spectrum of endometrial abnormalities that occur in women who use tamoxifen to treat or prevent the development of breast cancer. These abnormalities include endometrial polyps, endometrial hyperplasia, and endometrial carcinoma.
A biphenyl matrix metalloproteinase (MMP) inhibitor (MMPI) with potential antineoplastic activity. Tanomastat inhibits MMP-2, MMP-3, and MMP-9, inhibiting extracellular matrix degradation and potentially inhibiting angiogenesis, tumor growth and invasion, and metastasis. MMPs consist of at least 18 zinc-containing endo-proteinases that are capable of degrading collagen and proteoglycan.
Telomeres, which define the ends of chromosomes, consist of short, tandemly repeated DNA sequences loosely conserved in eukaryotes. Telomerase is a ribonucleoprotein complex which in vitro recognizes a single-stranded G-rich telomere primer and adds multiple telomeric repeats to its 3-prime end by using an RNA template. Telomerase may also have a role in de novo formation of telomeres. Telomerase has been identified in many cultured cell lines and actively dividing cell types. The active reverse transcriptase component has been identified as the TERT protein. The presence of this factor determines the availability of the telomerase function. The TERT protein has a high turnover rate and its expression is regulated by factors that promote growth (c-MYC, v-k-ras, Bcl-2, and E6) and inhibiting factors (RB and p53) that promote cell death or that block cell division. It appears that the regulation of active telomerase has many levels and can be inhibited by TEP1 not releasing TERT or by TRF1 which binds the end repeats and prevents access to the chromosome ends. Additional modulation is due to phosphorylation by PKC and AKT or dephosphorylation by PP2A. Human telomeres consist of many kilobases of (TTAGGG)n together with various associated proteins. Small amounts of these terminal sequences are lost from the tips of the chromosomes during each S phase because of incomplete DNA replication, but de novo addition of TTAGGG repeats by the enzyme telomerase compensates for this loss. Many human cells progressively lose terminal bases with each cell division, a loss that correlates with the apparent absence of telomerase in these cells. There has been considerable interest in the possible relationship between human telomeres and cellular senescence and immortalization. This interest includes the question of a role in the malignant process and the question of the use of telomerase inhibitors as anti-tumor drugs. (This definition may be outdated - see the DesignNote.)
Telomere Shortening occurs every time linear eukaryotic chromosomes are replicated due to premature stoppage of the DNA polymerase complex in the highly repetitive telomere DNA region several hundred bases before the end of a chromosome.
Telomerase is an enzyme that replicates the terminal sequences of eukaryotic chromosomes, namely the telomeres. Cells that have an unlimited replicative capacity, such as male germ cells and the majority of human cancers, have high levels of telomerase activity. The level and frequency of telomerase activity in more than 85% of all cancers highlights the critical role telomerase plays in tumor progression. Telomerase activation is the most common general marker for a cancer cell to date making it an attractive target for new cancer diagnostics and therapeutics. Human telomerase activity can be reconstituted in vitro by the essential RNA subunit, hTERC, and the catalytic protein component coded for by the hTERT gene. Both the human telomerase reverse transcriptase gene (hTERT) and the telomerase RNA gene (hTERC) are controlled at least in part at the transcriptional level. The hTERC gene is expressed at high levels in cancer cells, and is absent or at low levels in some normal tissues. (This definition may be outdated - see the DesignNote.)
Telomerase is an enzyme that replicates the terminal sequences of eukaryotic chromosomes, namely the telomeres. Cells that have an unlimited replicative capacity, such as male germ cells and the majority of human cancers, have high levels of telomerase activity. The level and frequency of telomerase activity in more than 85% of all cancers highlights the critical role telomerase plays in tumor progression. Telomerase activation is the most common general marker for a cancer cell to date making it an attractive target for new cancer diagnostics and therapeutics. Human telomerase activity can be reconstituted in vitro by the essential RNA subunit, hTERC, and the catalytic protein component coded for by the hTERT gene. Both the human telomerase reverse transcriptase gene (hTERT) and the telomerase RNA gene (hTERC) are controlled at least in part at the transcriptional level. The hTERT gene is expressed at low levels in cancer cells and is generally undetectable in normal cells. (This definition may be outdated - see the DesignNote.)
An uncommon usually benign neoplasm that arises from the testis. It is characterized by the presence of cysts lined by transitional cells and solid nests of transitional cells in a spindle cell stroma.
A benign neoplasm that arises from the testis and is characterized by the presence of fusiform cells and collagenization.
A testicular mixed germ cell-sex cord-stromal tumor. It is usually associated with mixed gonadal dysgenesis and ambiguous genitalia. It is characterized by the presence of nests of large neoplastic germ cells and immature cells that resemble Sertoli cells.
A rare sex cord-stromal tumor that arises from the testis in adults. Gynecomastia is present in approximately a quarter of the patients. Several morphologic patterns have been identified and include insular, gyriform, trabecular, pseudosarcomatous, and solid. Metastases occur in approximately twenty percent of the cases.
A rare sex cord-stromal tumor that arises from the testis. It is the most frequent congenital testicular neoplasm and is usually diagnosed during the perinatal period. It usually presents as an asymptomatic scrotal or abdominal mass. Morphologically it is characterized by the presence of cysts that are lined by cells resembling granulosa and theca cells.
A non-invasive lesion of the testis, characterized by the presence of malignant large germ cells with abundant cytoplasm in the seminiferous tubules. It may be associated with undescended or atrophic testis and infertility. The vast majority of cases progress to invasive germ cell tumors.
A testicular Sertoli cell tumor characterized by the presence of large polygonal cells with eosinophilic cytoplasm in a myxoid and hyalinized stroma. Calcifications may be present in the stroma.
A Leydig cell tumor characterized by a large size, cellular atypia, high mitotic activity, vascular invasion and necrotic changes. The prognosis is usually poor.
A malignant sex cord-gonadal stromal tumor that arises from the testis. It is characterized by cellular pleomorphism, anaplastic features, increased mitotic activity, and vascular invasion.
A choriocarcinoma that arises from the testis and is characterized by the predominance of cytotrophoblastic and intermediate trophoblastic cells. Syncytiotrophoblastic cells are absent or not prominent.
A rare testicular Sertoli cell tumor characterized by the presence of neoplastic tubules that are surrounded by a dense fibrotic stroma.
A morphologic variant of testicular seminoma characterized by the presence of seminoma cells arranged in cribriform patterns and few lymphocytes.
A morphologic variant of testicular seminoma characterized by the presence of seminoma cells arranged in pseudoglandular patterns and few lymphocytes.
A morphologic variant of testicular seminoma characterized by the presence of seminoma cells arranged in tubular patterns and few lymphocytes.
A testicular seminoma characterized by the presence of syncytiotrophoblastic giant cells.
A testicular Sertoli cell tumor in which the neoplastic cells have clear and vacuolated cytoplasm due to accumulation of intracytoplasmic lipids.
A malignant germ cell tumor that arises from the testis and is characterized by the presence of a spermatocytic seminomatous component which is contiguous with an undifferentiated or differentiated sarcomatous component. It usually presents as a slowly growing mass that enlarges very rapidly soon after the initial diagnosis.
A rare benign tumor that arises from the testis and is characterized by the presence of lipid-rich neoplastic spindle cells.
A tumor that arises from the testis and is composed of neoplastic trophoblastic cells. The vast majority of cases are choriocarcinomas.
A group of rare, slow-growing stromal tumors that arise from the testis. This category includes thecoma and fibroma.
A yolk sac tumor that arises from the testis and is characterized by the presence of connective tissue stalks that contain a blood vessel and are lined by cells with clear cytoplasm and prominent nucleoli.
A yolk sac tumor that arises from the testis and is characterized by the presence of immature glands.
A yolk sac tumor that arises from the testis and is characterized by the presence of gland-like spaces, irregular alveoli, and tubular structures.
A yolk sac tumor that arises from the testis and is characterized by the presence of hepatoid cells collections.
A yolk sac tumor that arises from the testis and is characterized by the presence of collections of thin-walled spaces.
A yolk sac tumor that arises from the testis and is characterized by the presence of a meshwork of small vacuolated cells resulting in a honeycomb appearance.
A yolk sac tumor that arises from the testis and is characterized by the presence of myxomatous tissue that contains collections of malignant cells with prominent nucleoli.
A yolk sac tumor that arises from the testis and is characterized by the presence of numerous papillary structures that are lined by cells with prominent nucleoli.
A yolk sac tumor that arises from the testis and is characterized by the presence of collections of vesicles that are surrounded by connective tissue.
A yolk sac tumor that arises from the testis and is characterized by the presence of aggregates of polygonal malignant cells with clear cytoplasm and prominent nucleoli.
Obtained by genetic engineering from the bacterial Clostridium tetani toxoid, tetanus toxoid helper peptide QYIKANSKFIGITEL (amino acids 830-844) binds to class II MHC molecules as a nonspecific vaccine helper epitope (adjuvant) and induces an increased (and long term) immune response by increasing the helper T-cell response. (NCI05)
A vaccine that contains detoxified tetanus toxin of Clostridium tetani. Aluminum phosphate is an adjunct that adsorbs the tetanus antigens to increase the half-life and immunogenicity of the vaccine.
CD4+ helper T cells differentiate into distinct subtypes, Th1 and Th2. Th2 cells are involved in the response to extracellular helminth parasites and allergic responses and secrete a distinct set of cytokines including IL-4, IL-5 and IL-13. The development and differentiation of T cells is influenced by many factors, including transcription factors such as GATA-3, a transcription factor associated with induction of Th2 cells. Factors that increase cAMP levels in Th2 cells activate p38 kinase, which phosphorylates and activates GATA-3 independently of PKA. Cells expressing GATA-3 develop the profile of Th2 cells, secreting IL-4, IL-5 and IL-13. These cytokines are found in a gene cluster together and are regulated coordinately by GATA-3. Binding of GATA-3 in the regulatory regions of these genes alters chromatin structure, increasing accessibility to other transcription factors. Activation of the T cell receptor through interaction with antigen on antigen presenting cells activates NFAT and other transcription factors that cooperate with GATA-3 in inducing Th2 cell differentiation. Dominant negative GATA-3 can repress the secretion of these cytokines and block the airway inflammation that causes asthma. Blocking GATA-3 action such as through antisense treatment has been suggested as a therapeutic strategy to treat asthma. GATA-3 has also been implicated in developmental processes such as the development of the inner ear. (This definition may be outdated - see the DesignNote.)
Any of the commercial combination preparations, by Novartis, containing a combination of any of the following agents: the analgesic antipyretic acetaminophen, an antihistamine (chlorpheniramine maleate, diphenhydramine hydrochloride, doxylamine succinate or pheniramine maleate), the antitussive dextromethorphan maleate and/or a decongestant (phenylephrine hydrochloride or pseudoephedrine hydrochloride). Theraflu preparations are used to relieve symptoms of cold and flu. Acetaminophen exerts its actions by inhibiting prostaglandin synthesis. The antihistamines block the effects of histamine. Dextromethorphan exerts its activity by raising the threshold for coughing in the cough center. The decongestants are sympathomimetic agents that cause vasoconstriction mediated through alpha-adrenergic receptors. This reduces blood flow, decreases swelling and prevents nasal and sinus congestion.
A therapeutic analogue of an endogenous, platelet-specific protein that is a member of the alpha chemokine family. Beta thromboglobulin may be used as a marker for platelet activation. (NCI04)
Formulated therapeutic analogs of one of a number of endogenous chemokines other than those classified as CXC, CC, C, or CX3C (previously known as alpha, beta, gamma, and delta, respectively). (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous epidermal growth factor (EGF). As a mitogen, EGF stimulates the proliferation of epidermal, epithelial, and embryonic cells. This agent is also a strong chemoattractant for fibroblasts and epithelial cells and is an important factor mediating angiogenesis and wound healing. EGF and EGF-like factors have been shown to promote regeneration of the epidermis and the generation of granulation tissues following severe burns and, when locally administered, may improve healing of injured corneal tissues. (NCI04)
A recombinant agent, which is chemically identical to or similar to the endogenous protein Fas ligand, a protein related to tumor necrosis factor (TNF) with potential antineoplastic activity. Fas ligand binds to the Fas receptor, thereby activating caspases and inducing apoptosis. (NCI04)
A recombinantly produced fibroblast growth factor family protein, with potential therapeutic applications.
Formulated therapeutic proteins that are either isolated from endogenous sources or manufactured in a laboratory. Growth factors bind to specific receptors expressed by various cell types, thereby stimulating cell differentiation and/or proliferation. (NCI04)
Drugs derived from hematopoietic growth factor that promote the development of blood cells.
A recombinantly produced form of the leukemia inhibitory factor protein. Endogenous leukemia inhibitory factor regulates neurogenesis and hematopoiesis.
A formulated therapeutic analog of the endogenous lymphokine leukoregulin with potential antineoplastic activity. Leukoregulin displays direct and indirect cytotoxicity through tumor cell lysis and enhancing tumor cell susceptibility to natural killer cell-mediated cytotoxicity. This agent enhances membrane permeability and decreases p-glycoprotein expression, thereby promoting cytotoxic drug uptake into tumor cells. Leukoregulin also induces the synthesis of collagenase and hyaluronan, expression and secretion of interleukin-8, and upregulates stromelysin-1 gene expression in human fibroblasts, thereby regulating extracellular matrix degradation. (NCI04)
Recombinant forms of endogenous neuropoietic cytokines.
Expressed in platelets, human Platelet-Derived Growth Factor (PDGF/VEGF Family) is a mitogenic factor for mesenchymal cells characterized by a motif of eight cysteines and released upon wounding to stimulate adjacent cell growth. PDGF can exist as antiparallel disulfide-linked homodimers (PDGFA, PDGFB) or heterodimers (PDGFA/PDGFB) that could bind to PDGF receptor and may elicit a variety of cellular responses. A and B homodimers are implicated in transformation processes. (NCI)
A recombinant form of the endogenous Transforming Growth Factor-Beta 1, a protein involved with the regulation of cell proliferation and differentiation.
A recombinant agent, which is chemically identical to or similar to the endogenous cytokine transforming growth factor-beta-3 (TGF-beta-3). TGF-beta-3 modulates cell growth and immune function and may promote or inhibit tumor growth, depending on the tumor cell type; this agent may also suppress host immune system recognition of and/or response to tumor cells. (NCI04)
An antimetabolite analogue of purine with antineoplastic and immuno-suppressant properties. 9H-Purine-6Thio-98D substitutes for the normal nucleoside and fraudulently incorporates into DNA and inhibits de novo purine synthesis, thereby inducing cell death. In vivo, this agent, also known as 6MP-arabinoside, may occur as a metabolite of the antineoplastic agent mercaptopurine. (NCI04)
A peptide vaccine derived from the von Hippel-Lindau (VHL) tumor suppressor protein, a general transcription factor. In (H115D)VHL35 peptide, histidine is substituted for an aspartic acid in position 115. It might be used to elicit or boost cellular immunity to cancers that expressing the von Hippel-Lindau mutation. (NCI04)
An oligonucleotide targeting the c-fos gene which decreases c-fos target mRNA and protein expression, thereby inducing differentiation and inhibiting cell proliferation. (NCI)
A molecular genetic abnormality indicating the presence of multiple copies of the MYC gene.
Any substance that inhibits cGMP phosphodiesterase, an enzyme that breaks the phosphodiester bond in cGMP. Inhibition of cGMP phosphodiesterase can be used to affect vasodilation.
This is an invalid term; lymphoblastic lymphomas are not chronic processes, but counterparts of acute lymphoblastic leukemias.
A chromosomal aberration where there is a loss of part of the long arm of chromosome 11, which deletes the chromosomal bands q22 and q23.
A cytogenetic abnormality that refers to the deletion of the chromosomal band 11q23.
A deletion of chromosomal material at 17p13. This chromosomal aberration includes deletion of the TP53 gene and is associated with multiple myeloma, chronic lymphocytic leukemia, acute myeloid leukemia and myelodysplastic syndrome.
A chromosomal deletion involving the p36 band of chromosome 1. This deletion is associated with 1p36 deletion syndrome.
Protein phosphorylation plays an important role in the control of translation by eukaryotic initiation factor-2 (eIF-2). eIF-2 binds GTP and Met-tRNAi and transfers the Met-tRNA to the 40S subunit, to form the 43S preinitiation complex. Later in the cycle, prior to elongation, the bound GTP is hydrolyzed, releasing eIF-2-GDP. For eIF-2 to promote another round of initiation, GDP must be exchanged for GTP, a reaction catalyzed by eIF-2B. Kinases activated by viral infection (PKR), endoplasmic reticulum stress (PERK/PEK), amino acid deprivation (GCN2), and hemin deficiency (HRI) can phosphorylate the a subunit of eIF-2. This phosphorylation stabilizes the eIF-2-GDP-eIF-2B complex, inhibiting the turnover of eIF-2B. eIF-2B is also inhibited by GSK-3b phosphorylation. These events result in a shut-down of cellular protein synthesis and can lead to apoptosis. (This definition may be outdated - see the DesignNote.)
eIF-4F and p70 S6 kinase play critical roles in translational regulation. eIF-4F is a complex whose functions include the recognition of the mRNA 5' cap structure (eIF-4E), delivery of an RNA helicase to the 5' region (eIF-4A), bridging of the mRNA and the ribosome (eIF-4G), and circularization of the mRNA via interaction between eIF-4G and the poly(A) binding protein (PABP). Several stimuli, including growth factors and cytokines, regulate the eIF-4 complex and p70 S6 kinase by initiating a phosphorylation cascade involving the sequential activation of PI3-K, PDK1/2, Akt/PKB, and FRAP/mTOR kinase. FRAP/mTOR, together with an unidentified kinase, phosphorylates 4E-BP, leading to its dissociation from and activation of eIF-4E. MNK1/2, activated by ERK and p38 MAPK, phosphorylates and activates eIF-4E. Both processes contribute to the association of eIF-4E and eIF-4G to form the active eIF-4F complex, a necessary component of the 48S initiation complex. Phosphorylation of ribosomal protein S6 by p70 S6 kinase stimulates the translation of mRNAs with a 5' oligopyrimidine tract which typically encode components of the protein synthesis. (This definition may be outdated - see the DesignNote.)
A recombinant HIV gp120 envelope protein with potential use in HIV vaccine therapy. Gp-120 antigen is used to elicit a gp120-specific T-cell response. (NCI04)
A cancer vaccine comprised of a recombinant fowlpox virus vector encoding the melanoma antigen glycoprotein 100 (gp 100) with potential antineoplastic activity. The expression of gp100 may generate a cellular immune response to melanoma cells; this effect is enhanced by the co-administration of interleukin 2 (IL-2). (NCI04)
A peptide consisting of amino acid residues 154 through 162 of the melanoma-melanocyte antigen gp100. Vaccination with gp100:154-162 peptide may enhance tumor-specific T-cell immunity. gp100 antigen is a self-antigen expressed by melanocytes, pigmented retinal cells, and most melanoma lesions and is recognized via class I and II HLA-restricted mechanisms.
A synthetic peptide vaccine consisting of amino acids 17 through 25 of the glycoprotein 100 (gp100) melanoma antigen. Vaccination with gp100_17-25 may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for gp100, resulting in decreased tumor growth. (NCI04)
A synthetic peptide vaccine consisting of the amino acids 209 through 217 of the glycoprotein 100 (gp100) melanoma antigen. Vaccination with gp100_209-217 may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for gp100, resulting in decreased tumor growth. (NCI04)
A vaccine consisting of the amino acids 280 through 288 of the melanoma antigen glycoprotein 100 (gp100) with potential antineoplastic activity. Vaccination with gp100:280-288 peptide may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the gp100 antigen, resulting in decreased tumor growth. (NCI04)
A synthetic peptide vaccine consisting of the amino acids 44 through 59 of the glycoprotein 100 (gp100) melanoma antigen. Vaccination with gp100_44-59 may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for gp100, resulting in decreased tumor growth. (NCI04)
A vaccine consisting of a replication-defective recombinant adenovirus that encodes the melanoma antigen glycoprotein 100 (gp100) with potential antineoplastic activity. Vaccination with gp100 adenovirus vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the gp100 antigen, resulting in decreased tumor growth. (NCI04)
A vaccine consisting of synthetic glycoprotein 100 (gp100) melanoma antigen and incomplete Freund's adjuvant (IFA), an emulsifying agent and immune system stimulant, with antineoplastic activity. Vaccination with gp100 human melanoma peptide vaccine with IFA may stimulate the host immune system to direct cytotoxic T lymphocytes (CTL) against gp100 positive melanoma cells, resulting in decreased tumor growth. (NCI04)
A vaccine consisting of a plasmid DNA encoding the human melanoma-associated antigen gp100. Upon administration, expressed gp100 antigen may stimulate a cytotoxic T cell HLA-A2.1-restricted immune response against tumor cells that express this antigen, resulting in tumor cell lysis. (NCI05)
A recombinant peptide derived from the human melanoma antigen glycoprotein 100 (gp100) with potential use in cancer immunotherapy. gp100 protein(184V) has a valine substitution at position 184. Vaccination with this peptide may evoke a cytotoxic T lymphocyte (CTL) response against tumor cells expression the gp100 antigen.
A cancer vaccine consisting of a recombinant vaccinia virus encoding the gp100 melanoma-melanocyte antigen. gp100 human antigen is a wild-type self-antigen expressed by melanocytes, pigmented retinal cells and most melanomas. (NCI04)
A vaccine consisting of microscopic gold particles coated with plasmid DNA encoding the glycoprotein 100 (gp100) melanoma antigen and granulocyte-macrophage colony-stimulating factor (GM-CSF). Vaccination with gp100 and GM-CSF DNA/gold vaccine may stimulate the host immune system to direct cytotoxic T lymphocytes (CTL) against gp100 positive cells, resulting in decreased tumor growth. GM-CSF is thought to increase the induction and activation of antigen-presenting cells (APC), allowing for a reduction in the dose of gp100 administered. (NCI04)
A synthetic agent derived from the tumor-associated differentiation antigen gp100 DNA. Gp100 DNA is coated onto microscopic gold beads and used to immunize animals and generate polyclonal antibodies that specifically recognize gp100 antigen. Gp100 human antigen is a non-mutated self-antigen - glycoprotein -expressed by melanocytes, pigmented retinal cells and most melanoma lesions, but is not expressed in other normal tissues or non-melanoma tumors. Immunization with human gp100 DNA may induce protective immunity against melanoma and may provide an effective approach for vaccine therapy with tumor-associated antigens against human melanoma. (NCI04)
A mutation in the SMARCB1 gene that either inhibits expression of the SMARCB1 protein or results in the translation of an inactive SMARCB1 protein.
The eukaryotic genome is packaged by histone and nonhistone proteins to form chromatin. The assembly of nucleosomes, as well as compaction of nucleosomal arrays into higher-order chromatin structures, creates a highly restrictive environment for nuclear processes that require access to DNA. The packaging of eukaryotic DNA into nucleosomes inhibits the access of factors to DNA and thus results in the repression of transcription, replication, and recombination. To counterbalance the repressive nature of chromatin, a variety of chromatin remodeling factors use the energy of ATP hydrolysis to facilitate the interaction of proteins with nucleosomal DNA. ATP dependent chromatin remodeling complexes are characterized by the presence of an ATPase subunit from the SNF2-like family of the DEAD/H (SF2) DNA-stimulated ATPases. The highly conservative hSWI/SNF multisubunit complexes contain hBRM or BRG1 ATPases which alter the histone-DNA contacts enabling the access of general transcription factors to promoter regions. Remodeling complexes are targeted to promoters via interactions with sequence-specific transcription factors. Since chromatin constitutes a barrier for processes affecting DNA, such a transcription, replication, and repair, a mechanism is required that can open up or remodel chromatin to make it accessible to replication and transcription factors. Steroid receptors are a class of transcription factors that can interact with the repressive chromatin structure and remodel the chromatin to allow other transcription factors to bind. In addition to nuclear receptors, transcription activators as divergent as erythroid Kruppel-like factor, C/EBPs, c-Myc, MyoD, HSF1, and EBNA2 have also been found to recruit SWI/SNF to specific promoters. The role of steroid receptors in chromatin remodeling and transcription is exemplified by the glucocorticoid receptor (GR)-mediated transactivation of the mouse mammary tumor virus (MMTV) promoter. The MMTV promoter is organized into a phased array of six nucleosomes when stably integrated into mammalian cells. The second nucleosome (nucB) is positioned over the binding sites for the GR and nuclear factor 1 (NF1). Binding of NF1 is essential for GR-mediated transactivation of the MMTV promoter; in the absence of glucocorticoid, the chromatin structure of the promoter excludes the binding of NF1. Upon hormone administration, GR recruits an ATP-dependent remodeling hSWI/SNF complex (BRG1-BAF) to remodel the chromatin Individually, the GR makes direct interactions with BRG1-associated factor 60a (BAF60a) and BAF57. Further, BAF60a possesses at least two interaction surfaces, one for GR and BRG1 and a second for BAF155 and BAF170.The remodeling process converts the closed conformation of the MMTV promoter to an open one without altering the nucleosomal positioning. The remodeling of the promoter permits NF1 binding and the assembly of a transcription initiation complex. (This definition may be outdated - see the DesignNote.)
A cytogenetic abnormality involving chromosome 17 that results from loss of the short arm and duplication of the long arm. This aberration is associated with a variety of neoplastic diseases, and is indicative of a poor prognosis for individuals with hematologic malignancies.
mTOR (mammalian target of rapamycin) appears to play a central role in signaling caused by nutrients and mitogens such as growth factors to regulate translation. The drug rapamycin acts on mammalian cells through the mTOR protein kinase, also known as FRAP. When bound to the immunophilin binding protein FKBP12, rapamycin inhibits mTOR kinase activity and has immunosuppressant activity. Rapamycin and the mTOR inhibitor CCI-779 are being tested as anti-cancer agents, acting to block mitogenic signaling. Recently, mTOR was also found to act as an ATP sensor to regulate cell growth. Upstream activation of PI 3 kinase activity that leads to oncogenic transformation can be blocked by inhibition of mTOR by rapamycin. Growth factor receptors first stimulate PI 3 kinase, and through inositol phosphates activate PDK-1 and AKT (protein kinase B). AKT phosphorylates mTOR. The phosphorylation of p70S6K and 4EBP by mTOR and the phosphorylation downstream of RPS6 and EIF-4B stimulate translational initiation and contribute to cell growth. (This definition may be outdated - see the DesignNote.)
Expression of a fusion protein with an apparent molecular weight of 190 kilodaltons that results from a fusion of the human genes BCR and ABL1.
Expression of a fusion protein with an apparent molecular weight of 210 kilodaltons that results from a fusion of the human genes BCR and ABL1.
Expression of a fusion protein with an apparent molecular weight of 230 kilodaltons that results from a fusion of the human genes BCR and ABL1.
p27/Kip1 regulates the cell cycle by inhibiting the checkpoint kinase cdk2/cyclin E and blocking cell cycle progression through the G1-S transition. Cancer cells in some cases have reduced levels of p27, supporting the importance of p27 in cell cycle regulation. The activity of p27 is regulated by phosphorylation, synthesis and degradation. Phosphorylation of p27 at threonine-187 by cdk2 causes p27 to associate with an SCF complex that targets p27 for proteolytic degradation. The F box protein Skp2 binds specifically to threonine-187 phosphorylated p27, recruiting it to the SCF complex for degradation. Other components of the p27 ubiquitin ligase complex include Skp1, Cul1, and Roc1/Rbx-1. Cks-1 has also been identified in a reconstituted system as an essential component for recruitment of p27 for degradation by the SCF complex. Signaling by cytokines may modulate cell survival, proliferation, or apoptosis through modulation of p27 expression. Cytokine and AKT signaling pathways activate forkhead transcription factors that induce p27 expression at the transcriptional level. (This definition may be outdated - see the DesignNote.)
p38 MAPKs are members of the MAPK family that are activated by a variety of environmental stresses and inflammatory cytokines. Stress signals are delivered to this cascade by members of small GTPases of the Rho family (Rac, Rho, and Cdc42). As with other MAPK cascades, the membrane-proximal component is a MAPKKK, typically a MEKK or a mixed lineage kinase (MLK). The MAPKKK phosphorylates and activates MKK3/5. The p38 MAPK kinase. MKK3/6 can also be activated directly by ASK1, which is stimulated by apoptotic stimuli. P38 MAK is involved in regulation of Hsp27 and MAPKAP-2 and several transcription factors including ATF2, STAT1, Max/Myc complex, MEF-2, ELK-1, and indirectly CREB via activation of MSK1. (This definition may be outdated - see the DesignNote.)
p53 is a transcription factor who's activity is regulated by phosphorylation. The function is p53 is to keep the cell from progressing through the cell cycle if there is damage to DNA present. It may do this in multiple ways from holding the cell at a checkpoint until repairs can be made to causing the cell to enter apoptosis if the damage cannot be repaired. The critical role of p53 is evidenced by the fact that it is mutated in a very large fraction of tumors from nearly all sources. (This definition may be outdated - see the DesignNote.)
A plasmid vector encoding interleukin-12 (IL-12) with potential use in the gene therapy of cancer. pNGVL3-hIL12 may induce a high level of IL-12 protein expression during transient transfection of host cells. IL-12 is a proinflammatory cytokine with numerous immunoregulatory functions and may augment host immune responses to tumor cells. (NCI04)
A synthetic fowlpox viral vaccine containing the tumor-associated antigens prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and a TRIad of COstimulatory Molecules (B7-1, ICAM-1 and LFA-3; TRICOM). Vaccination with this viral vaccine may enhance antigen presentation and activate cytotoxic T-cells against PSA- or PSMA-expressing tumor cells.
A cancer vaccine consisting of a recombinant fowlpox virus encoding fragment of human prostate-specific antigen (PSA), PSA:154-163 (155L), and a TRIad of COstimulatory Molecules (B7-1, ICAM-1 and LFA-3) (TRICOM). Administration of this agent may induce a cytotoxic T cell response against PSA-expressing tumor cells. Dendritic cells infected with TRICOM vectors greatly enhance naive T-cell activation and peptide-specific T-cell stimulation. Fowlpox virus is an attractive vector because its genome is easy to manipulate and it is replication incompetent in mammalian cells.
A cancer vaccine consisting of recombinant modified vaccinia Ankara (rMVA) encoding the prostate specific antigen (PSA), the prostate-specific membrane antigen (PSMA) and a TRIad of COstimulatory Molecules (B7-1, ICAM-1 and LFA-3) (TRICOM). Vaccination with PSA/PSMA in combination with TRICOM may enhance antigen presentation, resulting in the augmentation of a cytotoxic T cell (CTL) immune response against tumor cells over-expressing PSA or PSMA.
A vaccine formulation consisting of recombinant vaccinia virus encoding prostate specific antigen (PSA) and recombinant vaccinia virus encoding three co-stimulatory molecule transgenes B7.1, ICAM-1, and LFA-3 (TRICOM). Vaccination with PSA in combination with TRICOM may enhance antigen presentation, resulting in the augmentation of a cytotoxic T cell (CTL) immune response against tumor cells expressing PSA.
A synthetic lipid second messenger. As an analog of the second messenger diacylglycerol, sn-1,2-didecanoylglycerol substitutes for diacylglycerol in the cascade of calcium and phospholipid dependent PKC activation. Topical application of this agent results in a striking inflammatory response characterized by edema, extensive epidermal infiltration of neutrophils and macrophages, intraepidermal microabscesses. sn-1,2-Didecanoylglycerol is used as a tumor promoter in experimental animal models of skin cancer due to its stimulation of epidermal protein kinase C activity. (NCI04)
A cytogenetic abnormality that refers to the translocation of the short arm (p11) of chromosome 10 and the long arm (q23) of chromosome 11. It is associated with the development of acute myeloid leukemia with variant MLL translocations.
A chromosomal abnormality consisting of the translocation of 10q24 with 14q11, leading to inappropriate and abundant expression of HOX11 protein in T cells bearing the translocation.
A cytogenetic abnormality that refers to the translocation of the long arm (q13) of chromosome 11 and the long arm (q32) of chromosome 14. It results in up-regulation of cyclin D1 and is the most common translocation detected in multiple myeloma.
A cytogenetic abnormality that refers to the translocation of the long arm (q23) of chromosome 11 and the short arm (p13.1) of chromosome 19. It is associated with the development of acute myeloid leukemia with variant MLL translocations and topoisomerase II inhibitor-related acute myeloid leukemia.
A chromosomal abnormality consisting of the translocation of genetic material from any one of several chromosomes to the 11q23.3 region, resulting in an MLL gene rearrangement.
A chromosomal translocation that involves chromosome 12 and chromosome 16. It is often associated with the development of angiomatoid fibrous histiocytoma or myxoid liposarcoma.
A translocation between chromosomes 12 and 21 involved in TEL-AML1 oncogene formation. The translocation produces a chimeric gene encoding a protein consisting of the N-terminal HLH domain of the TEL ETS-like transcription factor fused with a nearly complete AML1 protein. t(12;21) is the most frequent translocation causing ALL, accounting for 20% of ALL cases.
A cytogenetic abnormality that refers to the a translocation involving the long arm (q13) of chromosome 12 and the long arm (q12) of chromosome 22.
A chromosomal translocation associated with creation of a fusion between the PML and RARA genes. It is seen in variants of acute promyelocytic leukemia.
A chromosomal abnormality consisting of the translocation of 19p13.3 with 1q23, resulting in the fusion of the TCF3 (E2A) gene with the PBX1 gene.
A chromosomal translocation associated with Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor and Olfactory Neuroblastoma.
A cytogenetic abnormality that refers to the translocation of the long arm (q25) of chromosome 3 and the long arm (q34) of chromosome 5. It is associated with the development of acute myeloid leukemia arising from myelodysplastic syndrome, acute myeloid leukemia with multilineage dysplasia, and acute myeloid leukemia with myelodysplasia-related changes.
A chromosomal abnormality consisting of the translocation of 4q21 with 11q23.
A cytogenetic abnormality that refers to the translocation of the long arm (q27) of chromosome 6 and the long arm (q23) of chromosome 11. It is associated with the development of de novo acute myeloid leukemia.
A chromosomal abnormality consisting of the translocation of 8q24 with 14q11, which juxtaposes the c-MYC gene with the gene for the T cell receptor alpha chain resulting in overexpression of c-MYC in T cells bearing the translocation.
A chromosomal translocation that fuses 8q24 with 14q32. This juxtaposes the MYC gene with the promoter regions of the immunoglobulin heavy chain gene locus, which results in overexpression of Myc proto-oncogene protein in B-cells bearing the translocation.
A cytogenetic abnormality that involves a translocation between 8q22 and 21q22. It is associated with the development of acute myeloid leukemia with RUNX1-RUNX1T1 fusion protein expression.
A cytogenetic abnormality that refers to the translocation of the short arm (p22.3) of chromosome 9 and the long arm (q23.3) of chromosome 11. It is associated with the development of acute myeloid leukemia with the MLLT3-MLL fusion gene transcript.
A translocation between chromosomes 9 and 22 that is associated with the Philadelphia chromosome.
A chromosomal translocation that involves the X chromosome and chromosome 18. It is often associated with the development of synovial sarcoma.
Programmed cell death is induced by many different factors and involves numerous signaling pathways, some dependent on caspase proteases and others that are caspase independent. Like cytochrome C, AIF (apoptosis-inducing factor) is a protein found in mitochondria that is released from mitochondria by apoptotic stimuli. While cytochrome C is linked to caspase-dependent apoptotic signaling, AIF release stimulates caspase-independent apoptosis, moving into the nucleus where it binds DNA. DNA binding by AIF stimulates chromatin condensation, and DNA fragmentation, perhaps through recruitment of nucleases. DNA-binding by AIF occurs through a distinct domain of the protein in a manner that does not rely on specific DNA sequences. AIF also has another domain that acts as an NADH oxidase, a redox enzyme. The NADH oxidase activity of AIF is separable from its DNA-binding activity and is not required for AIF to induce apoptosis. In this role, AIF protects against apoptosis rather than inducing apoptosis. In mice down regulation of the AIF gene created harlequin mice with oxidative damage to neurons and increased neuronal cell death. Loss of AIF also increased sensitivity to peroxides, suggesting that AIF may act as a peroxide scavenger. The mechanism by which AIF protects against peroxide damage is not clear, but may involve a more indirect mechanism than direct peroxide scavenging since the enzyme does not appear to have this activity in vitro. Elucidating further the role of AIF as a redox enzyme will shed further light on its normal function in mitochondria as well as its role in apoptosis and disease. (This definition may be outdated - see the DesignNote.)
Chromatin packaging of the genome is dynamic, changing with the cell cycle and with transcriptional regulation. During mitosis, chromatin is condensed for segregation of chromosomes, while for transcription chromatin is more open. The nuclear matrix, or scaffold, is a protein network in the nucleus providing structure and regulating chromatin condensation. Regulated interactions of matrix proteins with each other, DNA and other factors in different phases of the cell cycle alter the structure and function of chromatin. AKAP95 (A-kinase anchoring protein) is a nuclear matrix associated protein that also binds DNA and different proteins during different phases of the cell cycle. The interaction of AKAP95 with DNA and proteins alters the condensation and transcription of chromatin. A specific domain of AKAP95 regulates its interaction with the nuclear matrix and another regulates its association with DNA. One key protein that AKAP95 interacts with is the cAMP-dependent protein kinase, PKA. AKAP95 binds to PKA through a PKA RII regulatory subunit, an interaction that requires PKA phosphorylation by Cdk1. PKA activity and cAMP are reduced during entry into mitosis, but PKA recruited by AKAP95 to condensed chromosomes is essential to maintain the condensed state. Another protein recruited by AKAP95 is Eg7, a 150 kD protein recruited during mitotic chromatin condensation. Eg7 is a part of a multiprotein condensin complex, recruiting another key component of mitotic chromatin condensation. Modification of the core histones through phosphorylation regulates chromatin condensation. Histone H3 interacts with the condensin complex, and is phosphorylated during mitosis. Histone H3 phosphorylation by Aurora-2 induces chromatin condensation, and dephosphorylation by PP1 promotes chromatin decondensation for reentry into interphase. AKAP95 may play a role during the regulation of chromatin structure for transcription during interphase as well. The interaction of AKAP95 with the p68 RNA helicase recruits this enzyme to the nuclear matrix during interphase. Other nuclear RNA helicases interact with transcription factors and cofactors, suggesting that the p68 RNA helicase also may regulate interactions of transcription complexes. (This definition may be outdated - see the DesignNote.)
Many cell-surface receptors induce production of second messengers like PIP3, phosphatidylinositol 3,4,5-trisphosphate, that convey signals to the cytoplasm from the cell surface. PIP3 signals activate the kinase PDK1, 3-phosphoinositide-dependent protein kinase-1, which in turn activates the kinase AKT, also known as protein kinase B. Proteins phosphorylated by activated AKT promote cell survival. Phosphorylation of Ikappa-B kinase leads to activation of the transcription factor NF-kB to oppose apoptosis. Bad is a protein in the Bcl-2 gene family that opposes Bcl-2 to induce apoptosis. Phosphorylation of Bad by AKT blocks anti-apoptotic activity to promote cell survival. Similarly, phosphorylation of the protease caspase 9 or forkhead transcription factors by AKT block the induction of apoptosis by these factors. AKT promotes cell survival and opposes apoptosis by a variety of routes. (This definition may be outdated - see the DesignNote.)
Heart formation is cued by a combination of positive and negative signals from surrounding tissues. Inhibitory signals that block heart formation in anterior paraxial mesoderm include Wnt family members expressed in dorsal neural tube and anti-BMPs expressed in the axial tissues (i.e., noggin in the notochord). Wnt signaling pathway, which is essential for setting up the entire body pattern during embryonic development, involves glycogen synthase kinase-3 (GSK3). In the absence of Wnt signaling, GSK3 is active and phosphorylates b-catenin resulting in its degradation by ubiquitin-mediated proteolysis. Activation of Wnt signaling inhibits GSK3, thereby preventing phosphorylation of b-catenin, which is then able to move to the nucleus. There it associates with members of the LEF-1/TCF family of transcription factors, which activate the transcription of genes like cyclin-D1, myc, and MMPs. The Wnt signaling pathway is blocked by a family of secreted proteins such as crescent and Dkk-1 sufficient for induction of heart formation in posterior mesoderm. BMP signaling can also be blocked by the BMP antagonists noggin and chordin, which are secreted from the notochord and cooperate with Wnts to prevent cardiogenesis. Receptors for BMPs, members of the transforming growth factor-beta (TGFb) superfamily, are persistently expressed during cardiac development, yet mice lacking type II or type IA BMP receptors die at gastrulation and cannot be used to assess potential later roles in creation of the heart. Activin receptor-like kinase 3 (ALK3) is specifically required at mid-gestation for normal development of the trabeculae, compact myocardium, interventricular septum, and endocardial cushion. Cardiac muscle lacking ALK3 is specifically deficient in expressing TGFb2, an established paracrine mediator of cushion morphogenesis. In humans, congenital heart defects occur with a prevalence of at least 1% in newborns, and are even more common in death before term. Most frequent are defects in septation and the cardiac valves, and few single gene etiologies are known. The invariable defects in myocardium and AV cushion resulting from congenital deletion of ALK3 provide strong support for its assessment as a candidate gene in human congenital heart disease. (This definition may be outdated - see the DesignNote.)
A cancer vaccine consisting of ALVAC, a highly attenuated poxvirus strain derived from the canarypox virus. ALVAC-B7-CEA expresses carcinoembryonic antigen (CEA), a protein that is overexpressed by many tumor cells, and B7.1 (also known as CD80), the natural ligand for the T-cell antigen CD28, to augment the host immune response. This agent has been shown to stimulate a host immune response against tumor cells that express CEA. (NCI04)
A cancer vaccine consisting of ALVAC, a highly attenuated poxvirus strain derived from the canarypox virus. ALVAC-CEA (6D)-B7.1 vaccine expresses both a highly immunogenic analogue (6D) of the immunodominant epitope of carcinoembryonic antigen (CEA) and B7.1 (also known as CD80), the natural ligand for the T-cell antigen CD28. This agent was designed to stimulate host immune responses against tumor cells that express CEA. (NCI04)
A replication-defective recombinant canarypox virus (ALVAC) that contains the entire human carcinoembryonic antigen (CEA) gene. Vaccination with ALVAC-CEA (VCP248) may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against CEA-positive tumor cells, thereby decreasing tumor growth. (NCI04)
Expression of a fusion protein that results from a t(8;21)(q22;q22) translocation, which involves the human genes RUNX1 and RUNX1T1 and is associated with acute myeloid leukemia.
A cell-based vaccine targets tumors expressing the HER2/neu marker. HER-2/neu is a growth factor receptor, and its overexpression has been associated with a number of cancers including breast, ovarian, colon and lung cancers. APC8024 comprise of autologous antigen-presenting peripheral blood mononuclear cells (APCs) that have been exposed to HER2/neu protein and can be administered to the patient. These cells may stimulate an antitumor T-cell response to cancer cells expressing HER2/neu. (NCI04)
A vaccine made of antigens and antigen-presenting cells (APCs). APCs boost an immune response by presenting antigens on their surfaces to other cells of the immune system.
An unusual variant of acinar prostate adenocarcinoma characterized by the presence of neoplastic small atrophic glands that contain malignant cells with scant cytoplasm.
A variant of acinar prostate adenocarcinoma characterized by the presence of malignant cells with abundant xanthomatous appearing cytoplasm.
A variant of prostate carcinoma characterized by the presence of malignant cells forming syncytial patterns and dense lymphocytic infiltrates.
A variant of acinar prostate adenocarcinoma characterized by the presence of malignant large cells with granular eosinophilic cytoplasm.
A variant of acinar prostate adenocarcinoma characterized by the presence of neoplastic large glands that resemble the benign, non-neoplastic prostate glands.
A breast adenocarcinoma characterized by the presence of serous (acinic cell) differentiation.
Mammalian cell motility requires actin polymerization in the direction of movement to change membrane shape and extend cytoplasm into lamellipodia. The polymerization of actin to drive cell movement also involves branching of actin filaments into a network oriented with the growing ends of the fibers near the cell membrane. Manipulation of this process helps bacteria like Salmonella gain entry into cells they infect. Two of the proteins involved in the formation of Y branches and in cell motility are Arp2 and Arp3, both members of a large multiprotein complex containing several other polypeptides as well. The Arp2/3 complex is localized at the Y branch junction and induces actin polymerization. Activity of this complex is regulated by multiple different cell surface receptor signaling systems, activating WASP, and Arp2/3 in turn to cause changes in cell shape and cell motility. Wasp and its cousin Wave-1 interact with the Arp2/3 complex through the p21 component of the complex. The crystal structure of the Arp2/3 complex has revealed further insights into the nature of how the complex works. Activation by Wave-1, another member of the WASP family, also induces actin alterations in response to Rac1 signals upstream. Wave-1 is held in an inactive complex in the cytosol that is activated to allow Wave-1 to associate with Arp2/3. While WASP is activated by interaction with Cdc42, Wave-1, is activated by interaction with Rac1 and Nck. Wave-1 activation by Rac1 and Nck releases Wave-1 with Hspc300 to activate actin Y branching and polymerization by Arp2/3. Different members of this gene family may produce different actin cytoskeletal architectures. The immunological defects associated with mutation of the WASP gene, the Wiskott-Aldrich syndrome for which WASP was named, indicates the importance of this system for normal cellular function. (This definition may be outdated - see the DesignNote.)
A morphologic variant of embryonal rhabdomyosarcoma arising from the vagina. It is characterized by the formation of a cambium layer in the affected tissue and polypoid nodules with an abundant myxoid stroma. It occurs in female adults.
A vaccine composed of killed glioma cancer cells from another patient for use in immunotherapy.
An angiogenesis inhibitor that acts by blocking the action of alpha(v)beta integrins. An alpha(v)beta integrin inhibitor blocks the activity of an endothelial cell-surface expressed alpha(v)integrin, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis.
A salt or hydroxide mixture of aluminum and magnesium metals used as an antacid, aluminum magnesium absorbs and neutralizes stomach acid, helping to relieve intermittent, infrequent heartburn and indigestion. Aluminum and magnesium antiacids may be used to treat symptoms of peptic ulcer, gastritis, esophagitis, hiatal hernia and gastric hyperacidity. (NCI04)
Acetate salt of Ametantrone, a topoisomerase II inhibitor of the anthrapyrazole family that causes covalent cross-links in DNA.
Any substance that inhibits amidophosphoribosyltransferase, an enzyme that catalyzes the commiting step on de novo purine synthesis. Inhibition of amidophosphoribosyltransferase inhibits DNA synthesis and results in cell cycle arrest.
The lipid anandamide derived from arachidonic acid binds to the cannabinoid G-protein coupled receptors CB-1 and CB-2 to exert its biological effects. The CB-1 receptor is also the site of action of the psychoactive components of marijuana, including tetrahydrocannabinol (THC), and responsible for the effects of cannabinoids to repress learning, memory, and anxiety, relieve pain and nausea, and to stimulate appetite. The CB-2 receptor is expressed mainly in cells of the immune system and appears to modulate immune functions, but not to be involved in the effects of cannabinoids in the central nervous system. In addition to the illicit use of cannabinoids as drugs of abuse, the pharmaceutical use of natural and synthetic cannabinoids is being intensely studied, including a possible role in neurodegenerative diseases. Another therapeutic approach is the pharmacological modulation of levels of the endogenous cannabinoid anandamide. Although the subject of some controversy, the most likely route for the biosynthesis of anandamide starts with the formation of phosphatidylethanolamine from arachidonic acid and ethanolamine. Phosphatidylethanolamine is converted by N-acyltransferase to the phospholipid N-arachidonoyl-phosphatidylethanolamine (NAPE) and hydrolysis by phospholipase D releases phosphatidic acid and anandamide, which binds to the cannabinoid receptors. The signal it induces is terminated in part by degradation of anandamide by anandamide hydrolase (FAAH). 2-arachidonoyl-glycerol (2-AG) and 2-arachidonoyl glyceryl ether have also been shown to bind the cannabinoid receptors, and has been suggested to be important endocannabinoids. Also complicating cannabinoid pharmacology is the suggestion that some effects of cannabinoids might be moderated by additional receptor subtypes that have not yet been identified or by the vanilloid receptors. (This definition may be outdated - see the DesignNote.)
Oral leukoplakia associated with advanced dysplasia in which genetic studies show aneuploidy. The vast majority of patients develop aggressive invasive squamous cell carcinomas. Complete resection of the lesion does not reduce the risk of developing invasive squamous cell carcinoma.
An angiogenesis inhibitor that acts by blocking the action of endogenous pro-angiogenic substance(s).
Natural or synthetic Anti-glaucoma Agents relieve or prevent glaucoma, a condition characterized by increased intraocular pressure, excavation, and optic nerve damage. Such an agent may decrease ocular pressure and improve glaucoma as a beta-adrenergic blocker, a parasympathomimetic, an alpha-adrenergic agonist, a prostaglandin synthesis agonist, or by other mechanisms. (NCI04)
An agent that reduces plasma lipids, such as cholesterol or low density lipoproteins (LDL), acting systemically or locally (intestines) to decrease fat digestion, absorption, production, and accumulation in the plasma and reducing pathogenic atherosclerosis and thrombosis.
Used topically or systemically, natural or synthetic Anti-psoriatic agents relieve symptoms of psoriasis by controlling rapid growth of skin cells, reducing DNA synthesis and mitotic activity in hyperplastic epidermis, and restoring normal epidermal cell proliferation and keratinization. (NCI04)
Drugs which reduce the fatigue and weight loss often associated with cancer.
A process that involves the non-covalent binding of vasopressin to one of three arginine vasopressin receptor proteins. These interactions play a role in signaling pathways that modulate the maintenance of blood osmolality.
A key part of the immune system is the production of immunoglobulins (antibodies) by B cells to bind and inactivate specific foreign antigens. The body produces B cells with a wide range of antigen specificities in their immunoglobulin B cell receptor, but each cell only has a single specificity. When the B cell receptor immunoglobulin binds antigen, that cell is activated to proliferate and create plasma cells secreting immunoglobulins to bind that specific antigen. B cell activation also creates memory cells with the same antigen specificity that do not actively secrete immunoglobulin but provide for rapid future immune responses to the same antigen. B cells are not activated by antigen on their own, but require interaction with helper CD4+ T cells to become activated and proliferate. The B cell first expresses immunoglobulin on the cell surface as the B cell receptor. If the B cell receptor immunoglobulin binds specific antigen, then the cell internalizes the antigen and presents it to T cells in MHC II, where it is recognized by the T cell receptor. In addition to the interaction between the T cell receptor and the B cell MHC-antigen, T cell interaction with the B cell involves additional positive and negative regulatory signals. CD40 interaction with CD40L and CD28 interaction with CD80 provide positive costimulatory signals that stimulate B cell activation and proliferation. T cell receptor activation induces expression of molecules like the CD40 ligand that modulate the B cell-T cell interaction. The CD40-CD40L interaction induces cytokine production and expression of other genes and alters the fate of the B cell involved in the interaction. If the interaction between CD40 and CD40L is prolonged, the B cell can be induced to become a memory cell rather than a plasma cell. Fas ligand binding to Fas between B and T cells may negatively modulate B cell activation, inducing apoptosis that limits B cell proliferation and activation. Cytokines like IL-2, IL-4 and IL-10 also play an important role in B cell activation. (This definition may be outdated - see the DesignNote.)
Antigen Presentation Interaction involves specific non-covalent interaction (binding) through intermolecular physical forces of attraction and spatial complementarity of T-Cell Antigen Receptors with proteolytically processed fragments of antigenic foreign proteins displayed in association with self MHC antigens on the surface of antigen presenting macrophages.
Antigen Targeting involves specific and high affinity non-covalent interaction (binding) of an antibody reagent through intermolecular physical forces of attraction and spatial complementarity with a soluble or particulate substance (antigen) that induces an immune response. Using the keen specificity of antigen recognition by antibodies, targeting selectively localizes antibody-associated reagents to antigen sites for therapeutic or diagnostic effect.
Pharmaceutical Anti-gout Preparations such as colchicine, allopurinol, probenecid, and sulfinpyrazone contain natural or synthetic agents against gout, a condition characterized by increased uric acid accumulation. Anti-gout agents may reduce inflammation, stimulate elimination of uric acid, or increase production of uric acid. (NCI04)
Monoclonal antibody K4-2C10 conjugated with deglycosylated ricin A chain. This antibody recognizes human endoglin (Transforming Growth Factor P Receptor III), present on tumor vasculature.
Natural or synthetic Antihypertensive Preparations reduce elevated blood pressure through diverse mechanisms: calcium channel (and conductance) blockage, beta- and alpha-adrenergic blockage, angiotensin-converting enzyme inhibition, etc.. Their effects induce diuresis and peripheral vasodilation. (NCI04)
Treatment of cancer that utilizes antimetabolite substances to disrupt DNA, RNA, or protein synthesis.
An agent that prevents or impairs tumor metastasis.
Plant-derived compound used to treat cancer.
Used systemically or topically, natural or synthetic Antirheumatic Preparations relieve and control the symptoms of rheumatic diseases (rheumatoid arthritis) by reducing inflammation and pain, or reinstating mobility and function of articulations. Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive cytotoxics are examples of antirheumatic agents. (NCI04)
A tetracyclic diterpene antibiotic isolated from the fungus Cephalosporium aphidicola and other fungal species with potential antineoplastic activity. Aphidicoline glycinate blocks the cell cycle at early S-phase by specifically inhibiting DNA polymerases in eukaryotic cells, induces apoptosis, and stops the growth of eukaryotic cells and certain viruses by selectively inhibiting DNA polymerase II or viral-induced DNA polymerases. (NCI04)
The cellular activation of the caspase cascade resulting in cell death is triggered by chemical damage to DNA which stimulates a sequence resulting in the cleavage of BID or directly initiates the permeability transition of the mitochondrial membrane. The permeability transition releases several factors including cytochrome c, AIF and other factors in to the cytoplasm. Cytochrome c, a key protein in electron transport, is released from mitochondria in response to apoptotic signals, and activates Apaf-1, a protease released from mitochondria. Activated Apaf-1 activates caspase-9 and the rest of the caspase cascade. The caspases are a class of cysteine proteases that includes several representatives involved in apoptosis. The caspases convey the apoptotic signal in a proteolytic cascade, with caspases cleaving and activating other caspases that then degrade other cellular targets that lead to cell death. (This definition may be outdated - see the DesignNote.)
Apoptotic cell death can be triggered by many different cellular stimuli, resulting in activation of apoptotic signaling pathways including caspases and mitochondria. A cellular response that is characteristic of apoptosis is fragmentation of the nuclear genome to create a nucleosomal ladder. This activity is conducted by multiple nucleases activated by apoptotic signaling pathways. One nuclease involved in apoptosis is DNA fragmentation factor (DFF), a caspase-activated DNAse (CAD). DFF/CAD is activated through cleavage of its associated inhibitor ICAD by caspases proteases during apoptosis. DFF/CAD interacts with chromatin components such as topo II and histone H1 to condense chromatin structure and perhaps recruit CAD to chromatin. Another apoptosis activated protease is endonuclease G, EndoG. EndoG is encoded in the nuclear genome but is localized to mitochondria in normal cells. EndoG may play a role in the replication of the mitochondrial genome, as well as in apoptosis. Apoptotic signaling causes the release of EndoG from mitochondria. Mitochondria are involved in apoptotic signaling in other ways as well, through the release of cytochrome c induced by Bid to activate the caspase protease cascade. These pathways are independent since the EndoG pathway still occurs in cells lacking DFF. (This definition may be outdated - see the DesignNote.)
Containing natural or synthetic agents, Asthma Preparations relieve asthma (a recurrent airway obstruction) in various ways by reducing bronchial spasm, dyspnea, allergic reaction, local inflammation, and pain. Anti-asthmatic agents can be mainly bronchodilators (beta-adrenoreceptor agonists, xanthines, muscarinic-receptor antagonists) and anti-inflammatory agents (glucocorticoids, cromolyn). Other agents, such as anti-histamines and antibiotics, may be used in asthma preparations. (NCI04)
Stage I includes: (T1, N0, M0) and (T2, N0, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.)
Stage I includes: (T1, N0, M0) and (T2, N0, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. (AJCC 6th ed.)
Live vaccines prepared from microorganisms which have undergone physical adaptation (e.g., by radiation or temperature conditioning) or serial passage in laboratory animal hosts or infected tissue/cell cultures, in order to produce avirulent mutant strains capable of inducing protective immunity. Live-attenuated vaccines are used when a CD8+ T Cell (cellular cytotoxicity) response is desired.
The G-protein coupled receptor (GPCR) family transduces extracellular signals across the plasma membrane, activating cellular responses through a variety of second messenger cascades (see PKA and PKC signaling pathways). These receptors provide rapid responses to a variety of stimuli, and are often rapidly attenuated in their signaling. Failure to attenuate GPCR signaling can have dramatic consequences. One method to attenuate GPCR signaling is by removal of the stimulus from the extracellular fluid. At the synapse, removal of neurotransmitter or peptide signaling molecules is accomplished by either reuptake or degradation. Acetylcholine is removed from synapses through degradation by the enzyme acetylcholinesterase. Inhibition of acetylcholinesterase results in prolonged signaling at the neuromuscular junction, and uncontrollable spasms in humans caused by nerve gas or in insects by some insecticides. Inhibition of acetylcholinesterase is also used therapeutically to treat Alzheimer's disease, compensating for the loss of cholinergic neurons. Transporters for serotonin, dopamine, GABA and noradrenaline remove these neurotransmitters from the synapse to terminate signaling. Antidepressants such as Prozac inhibit reuptake of serotonin and many drugs of abuse such as cocaine act by blocking reuptake of dopamine or adrenaline. Reuptake not only terminates signaling, but can also conserve neurotransmitter through recycling back into the presynaptic cell. The next step in the attenuation of GPCR signaling is receptor desensitization, in which receptors are modified to no longer transduce a signal even if the stimulus is still present. Desensitization of GPCRs occurs through protein kinases that phosphorylate the GPCR to turn off signaling. Downstream protein kinases such as PKA and PKC turned on by GPCR signaling can phosphorylate the activated GPCR and other GPCRs to prevent further signaling. G-protein receptor kinases (GRKs) are a family of kinases that specifically phosphorylate only agonist-occupied GPCRs. GRKs attenuate GPCR signaling in concert with arrestins, proteins that bind GRK-phosphorylated GPCRs to disrupt interaction with G-protein and to terminate signaling. Reducing the number of receptor expressed on the cell surface can also attenuate receptor signaling. Many GPCRs are removed from the cell surface by receptor-mediated endocytosis when they are activated. Endocytosis of activated GPCRs appears to be stimulated by GRKs and arrestins. Once internalized, receptors can either be degraded in lysosomes or they can be recycled back to the cell surface. (This definition may be outdated - see the DesignNote.)
Malignant transformation and proliferation of B lymphocytes.
An allogenic whole tumor cell vaccine with potential antineoplastic activity. B7 transfected melanoma cell vaccine consists of melanoma cells that have been induced to express the human leukocyte antigen (HLA) B7. Vaccination with these altered cells may elicit an anti-tumor immune response via CD8+ cytotoxic T lymphocytes (CTL). (NCI04)
The function of the pro-apoptotic molecule BAD is regulated by phosphorylation of three sites (ser 112, 136, and 155). Phosphorylation at these sites results in loss of the ability of BAD to heterodimerize with the survival proteins BCL-XL or BCL-2. Phosphorylated BAD binds to 14-3-3 and is sequestered in the cytoplasm. While ser-136 phosphorylation is concordant with the activation of Akt, Ser-112 phosphorylation requires activation of the Ras-MAPK pathway. BAD Ser 155 was found to be a major site of phosphorylation induced following stimulation by growth factors and prevented by protein kinase A inhibitors. (This definition may be outdated - see the DesignNote.)
BRCA1 is a breast and ovarian cancer tumor suppressor protein that associates with BARD1 to form a RING/RING heterodimer. The BRCA1/BARD1 RING complex functions as an ubiquitin (Ub) ligase with activity substantially greater than individual BRCA1 or BARD1 subunits. The BRCA1 tumor suppressor forms a heterodimer with the BARD1 protein, and the resulting complex functions as an E3 ubiquitin ligase that catalyzes the synthesis of polyubiquitin chains. UbcH5c and UbcH7 also interact with the BRCA1/BARD1 complex with similar affinity (not shown on this figure). Although the in vivo substrate(s) is not yet known, BRCA1 has been observed to undergo autoubiquitination and is capable of monoubiquitinating histones 2A and 2AX in vitro. (This definition may be outdated - see the DesignNote.)
A niacinamide and phenylurea derivative that inhibits multiple intracellular and cell surface kinases thought to be involved in ANGIOGENESIS, including RAF KINASES and VEGF RECEPTORS. It is used in the treatment of advanced RENAL CELL CARCINOMA and HEPATOCELLULAR CARCINOMA, and for treatment of THYROID CARCINOMA refractory to radioactive iodine therapy.
A mycobacterial cell wall material and serves as an immunoadjuvant that induces both cell-mediated and humoral immunity.
A purified Keyhole Limpet Hemocyanin, a potent antigenic protein capable of eliciting both humoral and cellular immune responses against tumor cells.
A cytogenetic abnormality that refers to any translocation involving the BCL2 gene.
Bcr/abl is the gene rearrangement that is associated primarily with the disease chronic myelogenous leukemia and less frequently with acute lymphoblastic leukemia. This rearrangement results in the formation of the BCR-ABL1 fusion protein.
The differentiation of keratinocytes constantly replenishes the upper layers of human skin we lose each day. One factor that contributes to terminal keratinocyte differentiation is increased levels of intracellular calcium. Adding calcium to the medium of cultured keratinocytes elevates intracellular calcium and triggers differentiation. Intracellular calcium levels are also increased in response to phospholipase C activation, producing IP3 and releasing calcium from stores in the ER. Intracellular calcium alters multiple signaling pathways, one of which is binding to calmodulin to activate the serine-threonine protein phosphatase calcineurin. Calcineurin dephosphorylates and activates the transcription factor NFAT and both calcineurin and NFAT are expressed in differentiating keratinocytes. Activated NFAT can regulate transcription through binding its own cognate DNA binding site. One marker of keratinocyte differentiation, the p21 gene, is activated by NFAT by a different mechanism, with NFAT activating the p21 promoter by acting as a coactivator for the transcription factors Sp1 and Sp3.Another protein activated by calcium that may be involved in keratinocyte differentiation is protein kinase C (PKC). One substrate of activated PKC is MARCKS (myristoylated alanine-rich kinase C substrate). Phosphorylation of MARCKS by PKC in intact keratinocytes is not induced during calcium-induced differentiation, but does increase when tested in vitro. PKC activity is increased by calcium during keratinocyte differentiation but PKC MARCKS phosphorylation is blocked by the formation of a complex between calmodulin and MARCKS. The immunosuppressants cyclosporin-A (CsA) and FK506 inhibit T cell activation through indirect inhibition of NFAT activation and have several side effects including changes in the skin, suggesting that calcineurin activity may play a role in normal skin physiology. CsA is used to treat psoriasis, a disease involving abnormal proliferation of skin cells. The activity of CsA in treating psoriasis may involve inhibition of immune cells, but may also directly involve inhibition of calcineurin activity in keratinocytes. (This definition may be outdated - see the DesignNote.)
Calcium Binding consists of a biophysical interaction between one or more calcium ion(s) and a biological molecule, such as a protein. Calcium binding with proteins often involves interaction of the ion(s) with a specific region, domain, or motif (e.g., EF-Hand) that supports protein structure or induces an alteration of protein activity in enzymatic or cell signaling cascades.
A process that involves the binding of a cognate ligand to a member of the calcium channel receptor family. These interactions are involved in the release of calcium from intracellular stores.
The calcium/calmodulin-dependent kinases (CaMKs) are involved in a large number of cellular responses induced by hormones, neurotransmitters and other signaling. Elevation of calcium functions as a major second messenger, where the intracellular concentration of calcium can be maintained at extremely low levels and subsequently increased following specific calcium-mobilizing stimuli. There are many buffers to the calcium fluctuations including membrane pumps and calcium-binding proteins that create discrete spatial control of its effectors and their targets. The current family of multifunctional calcium/calmodulin (CaM)-dependent protein kinases (CaMKs) consists of CaMKI, CaMKII and CaMKIV. These kinases translate and co-ordinate the calcium fluctuations into the appropriate cellular responses via phosphorylation. These kinases are partially regulated by the intracellular calcium receptor calmodulin (CaM), and have common as well as unique features in their structure, regulation and activation. CaMKII, CaMKI and CaMKIV, have an autoregulatory domain that restricts or inhibits enzymatic activity in the absence of calcium/CaM. Calcium/CaM binding alone produces maximal activity of CaMKII, whereas CaMKI and CaMKIV have an activation loop that requires phosphorylation of a threonine residue by CaMK kinase (CaMKK) for maximal activity. Two genes (alpha and beta) for CaMKK, which is also regulated by CaM, have been identified. The highest expression of these isoforms occurs in the brain but the activity of the CaMKs has been identified in most cell types. CaMKIV has a post-calmodulin autophosphorylation step that is not observed in CaMKI. The CaMKII multimer can autophosphorylate either the autoregulatory domain or the CaM-binding domain, producing diverse effects in its regulation and sensitivity to Calcium/CaM. Autophosphorylation of CaMKII can produce Calcium/CaM- independent activity (autonomous activity), without affecting its maximal Calcium/CaM-stimulated activity. The CaMKII autophosphorylation involves a kinase cascade of sorts, with each subunit of the multimeric enzyme acting as both kinase and kinase kinase. Autophosphorylation establishes a 1000-fold increase in the affinity for its activator Calcium/CaM (also known as CaM trapping); however, autophosphorylation within the CaM-binding domain following CaM dissociation of activated/autophosphorylated enzyme restricts or prevents CaM from rebinding (CaM capping). The mechanisms and consequences of autophosphorylation are central to the CaMKII enzyme's complex regulatory behavior enabling it to become differentially activated at different frequencies and levels of calcium spikes. The target proteins for the CaMKs are very similar. An example target of the CaMKs is the transcriptional activating protein CREB. The phosphorylation states of CREB after CaMK phosphorylation differ by the additional phosphorylation of CREB at serine 142 that functions as an additional inhibitory site. This difference appears to be the result of adjacent amino acids. (This definition may be outdated - see the DesignNote.)
The sodium salt of camptothecin, an alkaloid isolated from the Chinese tree Camptotheca acuminata, with antineoplastic activity. During the S phase of the cell cycle, camptothecin selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. The sodium salt of camptothecin is more water-soluble than the parent molecule. (NCI04)
Any of the genetically engineered live canarypox vectors with application in anti-cancer therapy. Canarypox vectors retain the pancytotropism of most poxviruses, but is unable to productively replicate in non-avian species, thus eliminating the safety concerns exist with other vectors. Canarypox viral vector is designed to carry a gene of interest into a eukaryotic cell where the gene of interest can be expressed subsequently.
The unregulated growth of cancer cells insofar as growth control and contact inhibition.
Control of the rate or manner of occurrence of the complex series of phenomena occurring after division and before death of cancer cells. (NCI)
Any gene mutation that promotes neoplastic cellular transformation. Cancer gene mutations include both activation of oncogenes and inactivation of tumor suppressor genes.
An elaboration of a sequence of biological or biochemical events that play a role in the metabolism of carbohydrates.
An agent that interferes with the intracellular glycoprotein glycosylation pathway. Intracellular glycosylation of glycoproteins is involved in many cellular processes, including lymphocyte trafficking, immune cell stimulation, embryogenesis, and cancer metastasis. (NCI04)
A cancer vaccine comprised of an epitope from the Carcinoembryonic Antigen obtained from cancer cells that can stimulate an immune response against tumor cells. (NCI)
The sum of the chemical and physical changes occurring in tissue and resulting in biodegradation of any cancer-producing substance or organism.
The natural or acquired ability of an organism to maintain its immunity to or to resist the effects of a cancer causing agent.
Apoptosis, programmed cell death, is triggered by a variety of stimuli, including cell surface receptors like FAS, mitochondrial response to stress, and cytotoxic T cells. Caspases are a class of cysteine proteases that includes several representatives involved in apoptosis. The caspases convey the apoptotic signal in a proteolytic cascade, with caspases cleaving and activating other caspases that then degrade other cellular targets that lead to cell death. The caspases at the upper end of the cascade include caspase-8 and caspase-9. Caspase-8 is the initial caspase involved in response to receptors with a death domain like FAS. The mitochondrial stress pathway begins with the release of cytochrome c from mitochondria, which then interacts with Apaf-1, causing self-cleavage and activation of caspase-9. Caspase-3, -6, and -7 are downstream caspases that are activated by the upstream proteases and act themselves to cleave cellular targets. Granzyme B and perforin proteins released by cytotoxic T cells induce apoptosis in target cells, forming transmembrane pores, and triggering apoptosis, perhaps through cleavage of caspases, although caspase-independent mechanisms of Granzyme B mediated apoptosis have been suggested. (This definition may be outdated - see the DesignNote.)
Any substance that inhibits a caspase-family protease. Caspases play a key role in apoptosis as well as in inflammation and immune regulation. Caspase inhibition can be used to regulate these processes.
Any type of stress response signaling that results in modification to the process of cell death.
An agent that either induces or inhibits the differentiation or maturation of cells, specifically neoplastic cells, resulting in decreases in tumor growth and metastasis. (NCI04)
Any subcellular process that is initated by a chemical or mechanical stimulus and results in a specific cellular response.
Cellular or subcellular processes involved in disturbance or restoration of a homeostatic condition. (NCI)
Interactions between cells, responsible for cell to cell adhesion, can communicate signals into the cellular interior. These signals often involve interactions with cytoskeletal elements to produce changes in cell motility, migration, proliferation and shape. The cadherins are cell surface adhesion molecules that help form tight junctions between cells, such as in formation of epithelial cell layers. E-cadherin inactivation has been implicated in cancer development. In addition to mediating adhesion with other cells, cadherins transduce signals into cells through interactions with the catenins. Catenins probably affect actin cytoskeletal function through interactions with proteins such as actinin and vinculin. Catenins also probably trigger changes in cell shape and motility by signals through the Rho small GTPases. Another important cell adhesion molecule is CD-31, or PECAM-1, involved in the formation of junctions between endothelial cells, cell migration, migration of lymphocytes, and regulation of lymphocyte activation. Src phosphorylates PECAM-1 on tyrosine residues causing SHP-2 association with PECAM-1. Paxillin acts as an adaptor protein between proteins involved in adhesion signaling like FAK and src and cytoskeletal elements. In addition to signals created by adhesion molecules to alter cellular responses, other signaling pathways can alter adhesion through components of the focal adhesion complex. (This definition may be outdated - see the DesignNote.)
A neurofibroma characterized by the presence of areas with increased cellularity.
Cellular or subcellular processes involved with significant disturbance from a homeostatic condition. (NCI)
Protein kinase A regulatory subunit RII-alpha (PKA-RIIa) is tightly bound to centrosomal structures during interphase through interaction with the A-kinase anchoring protein AKAP350 (also known as AKAP450 and CGNAP), MAP2 and Pericentrin. This diagram illustrates these three PKA-RII binding complexes. The cyclin B-p34(cdc2) kinase (CDK1) has been shown to phosphorylate PKA-RIIa on T54 and this has been proposed to alter the subcellular localization of PKA-RIIa at the onset of mitosis. It has been demonstrated that PKA-RIIa dissociates and redistributes from centrosomes at mitosis. The focal point of this illustration is the AKAP350 complex. In addition to binding PKA-RIIa, AKAP350 binds PKN (Takahashi et al 1999) and the phosphatases PP1 and PPA2 (Takahashi et al 1999). PKN is a serine/threonine protein kinase, having a catalytic domain homologous to the PKC family in the C-terminal region and a unique regulatory region in the N-terminal region. PKN is activated by a small GTPase RhoA and unsaturated fatty acids such as arachidonic acid. The binding of both kinases and phosphatases by the same scaffold protein provides a focal point where physiological events, such as cell cycle progression and intracellular membrane traffic, may be regulated by phosphorylation state of specific protein substrates. There are at least 4 isoforms of AKAP350 which lead to the possibility that they may behave differently at different subcellular locations. MAP2 is a member of a group of proteins that provide microtubule stabilization. MAP2 affinity appears to be dependent on PKA phosphorylation of MAP2. Pericentrin is also an AKAP (Diviani and Scott). Pericentrin binds Dynein which is also regulated by PKA leading to the possibility that pericentrin positions PKA to regulate dynein function (Diviani and Scott). (This definition may be outdated - see the DesignNote.)
The cephalostatins comprise a family of more than 30 trisdecacyclic bissteroidal pyrazines with extreme cytotoxicity against human tumors, isolated from the African marine worm Cephalodiscus gilchristi. The mechanism of action of these compounds remains unknown. Beside a steroidal platform, critical features implicated in the pharmacophore include a set of covalently linked polar and nonpolar domains and the spiroketals. It was shown that cephalostatin 1 induces a novel pathway of receptor-independent apoptosis that selectively uses Smac/DIABLO (second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with a low isoelectric point) as a mitochondrial signaling molecule. Apoptosis was found to be dependent on caspase activity because the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone blocks cephalostatin 1-mediated DNA fragmentation. (NCI)
Ceramide is a sphingosine-based lipid-signaling molecule involved in the regulation of cellular differentiation, proliferation, and apoptosis. This diagram represents some of the current understanding of the cascades that couple ceramide to specific signaling pathways. These cascades illustrate that ceramide can be a growth stimulus or proapoptotic signal. The ultimate ceramide action is determined within the context of other stimuli and by the subcellular topology of its production and is cell-type specific. There are 2 forms of sphingomyelinase, acid (acid-sphingomyelinase, A-SMase) and neutral (neutral-sphingomyelinase, N-SMase), that can produce ceramide. TNF-alpha can stimulate either form of sphingomyelinase as can other death receptors. Different domains of TNF-alpha stimulate the different SMases. N-SMase stimulation is enhanced by the receptor for activated-C kinase 1 (RACK1). The activity of each form is dependent on the local intracellular pH. In the illustration the forms are separated to reduce confusion however ceramide produced by either method can stimulate either cascade depending on the presence of specific co-factors and activators. A-SMase has been recognized as one of the required molecules to mediate proapoptotic signaling in cell death induced by a diverse array of stresses such as H2O2, Heat, UV exposure and Radiation. ROS generation in mitochondria activates caspase-3 via cooperation of cytochrome c, Aif and caspase-9 and stimulates or increases ceramide generation through A-SMase in a proapoptotic activation cycle. Caspase-3 further increases its own activation by proteolytically cleaving ceramide inhibited catalase which is an inhibitor of ROS generation. Ceramide-activated protein kinase(CARK) also known as Kinase Suppressor of RAS (KSR) activity is in some cases the switch point in the balance between proapoptotic and antiapoptotic signals and is also cell-type specific. In endothelial cells for example the activation of KSR is required for apoptosis. In contrast in epithelial cells activation of KSR is required for cell proliferation. An additional switch point is the availability of Bad in the cell. Activation of KSR leads to further mitochondrial stimulation or association with RAS and activation of the Raf1 cascade leading to proliferation or differentiation. (This definition may be outdated - see the DesignNote.)
A benign, polypoid neoplasm that arises from the cervix. It is characterized by the presence of epithelial and mesenchymal elements.
A rare low grade carcinoma that arises from the cervix. It is characterized by the presence of nests of basaloid cells with focal glandular formations.
A rare, benign, usually polypoid neoplasm that arises from the cervix. It is characterized by the presence of a glandular component and a smooth muscle cell component. Variants include the endocervical type, endometrial type, and atypical polypoid adenomyoma.
An adenomyoma that arises from the cervix and is characterized by the presence of endocervical mucinous glands and a smooth muscle cell component. There is no atypia or significant mitotic activity present.
An adenomyoma that arises from the cervix and is characterized by the presence of endometrial type glands and endometrial stroma, surrounded by smooth muscle. There is no evidence of atypia.
A poorly differentiated variant of adenosquamous carcinoma that arises from the cervix. It is characterized by the presence of large malignant cells with ground glass cytoplasm and stromal eosinophilic infiltrates.
An alveolar soft part sarcoma arising from the cervix.
An adenomyoma that arises from the cervix and is characterized by the presence of a glandular component exhibiting architectural complexity.
A nevus that arises from the cervix. It is characterized by the presence of benign, heavily pigmented dendritic melanocytes.
A usually solitary polypoid lesion that arises from the cervix. It usually affects women in their reproductive years. It is characterized by the presence of a connective tissue core and overlying epithelium.
A benign, malignant, or precancerous neoplasm that arises from the glandular epithelium of the cervix. Representative examples include endocervical polyp, cervical adenocarcinoma, and cervical glandular intraepithelial neoplasia.
A rare, aggressive neuroendocrine carcinoma that arises from the cervix and is characterized by the presence of malignant cells with abundant cytoplasm, large nuclei, and prominent nucleoli.
A variant of cervical squamous cell carcinoma characterized by the presence of islands of cells with uniform, vesicular nuclei and prominent nucleoli and a dense lymphocytic infiltrate.
A cervical adenocarcinoma that arises from mesonephric remnants. It is usually characterized by the presence of tubular glands lined by cuboidal epithelial cells.
A benign or malignant neoplasm that arises from the cervix and is characterized by the presence of epithelial and mesenchymal elements. This category includes adenofibroma, adenomyoma, adenosarcoma, and carcinosarcoma.
A cervical mucinous adenocarcinoma characterized by the presence of malignant glandular cells that resemble those of the endocervix.
A cervical mucinous adenocarcinoma that resembles the large intestinal adenocarcinoma.
A rare, extremely well differentiated cervical mucinous adenocarcinoma in which most of the neoplastic glands cannot be distinguished from the normal endocervical glands.
A rare cervical mucinous adenocarcinoma characterized by the presence of signet ring cells.
A rare malignant mixed epithelial and mesenchymal neoplasm that arises from the cervix and is characterized by the presence of malignant mesenchymal elements and benign epithelial elements.
A rare, benign, papillary neoplasm that arises from the cervix. It is characterized by the presence of a fibrovascular core covered by mucinous epithelial cells.
A human papillomavirus-related cervical squamous cell carcinoma characterized by the presence of papillary structures covered with epithelial cells which show features of cervical intraepithelial neoplasia. The malignant cellular component below the papillary structures is a squamous cell carcinoma.
A rare benign skeletal muscle neoplasm arising from the cervix. It is characterized by the presence of small nucleated rhabdomyoblasts within a fibrous and myxoid stroma.
A rare adenocarcinoma that arises from the cervix. It is characterized by the presence of papillary patterns and cellular budding. Psammoma bodies are often seen.
A benign or malignant mesenchymal neoplasm of the cervix. Representative examples include rhabdomyoma, alveolar soft part sarcoma, and AIDS-related Kaposi sarcoma.
A human papillomavirus-related cervical squamous cell carcinoma characterized by the presence of papillary structures with fibrovascular cores. It is covered with multiple layers of atypical cells that resemble cervical intraepithelial neoplasia 3.
A benign, precancerous, or malignant neoplasm that arises from the squamous epithelium of the cervix. Representative examples include condyloma acuminatum, cervical intraepithelial neoplasia, and squamous cell carcinoma.
A highly differentiated variant of cervical squamous cell carcinoma characterized by the presence of a warty surface and stromal invasion with pushing borders. The malignant cells have abundant cytoplasm and minimal nuclear atypia. Koilocytosis is not present.
A human papillomavirus-related cervical squamous cell carcinoma characterized by the presence of a warty surface and koilocytotic atypia.
An embryonal neoplasm arising from the cervix with morphologic features resembling Wilms tumor of the kidney.
Although insulin and glucagon play important roles in regulating the response of cells to nutrients, cells also respond to carbohydrates through transcriptional regulation by the glucose responsive transcription factor ChREBP. ChREBP, carbohydrate responsive element binding protein, is a transcription factor that is activated by high levels of carbohydrates and repressed by cAMP. The activation of ChREBP by elevated carbohydrate levels increases the activity of genes involved in glucose metabolism such as pyruvate kinase, a rate-limiting enzyme in glycolysis, increasing the overall rate of utilization of carbohydrates. Excess carbohydrates also increase the transcription of genes that convert carbohydrates to triglycerides in the liver for storage in adipose tissue. cAMP regulates ChREBP activity by activating PKA, which phosphorylates ChREBP. Phosphorylation of ChREBP at ser(196) inactivates nuclear import and phosphorylation at Thr(666) prevents DNA binding by ChREBP. A metabolite of glucose activates protein phosphatase PP2A that then dephosphorylates both sites on ChREBP in response to increased glucose levels and increases ChREBP activity. Other pathways also regulate ChREBP activity and response to nutrients. High fat diets repress ChREBP activation by increasing AMP in liver cells, activating the AMP kinase. Phosphorylation of ChREBP by AMP kinase inactivates ChREBP and blocks glucose induction of ChREBP, linking dietary fatty acids to the regulation of carbohydrate metabolism. (This definition may be outdated - see the DesignNote.)
Chaperone Protein Inhibition involves interference with, or restraint of, the activities of diverse cellular proteins that noncovalently bind to nascent or unfolded polypeptides and mediate assembly/disassembly, stability, and transmembrane translocation of other polypeptides or complexes, but which are not components of those structures.
Chaperone Protein Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction by cellular proteins that mediate assembly/disassembly, stabilization, and transmembrane translocation of other polypeptides or complexes, but which are not components of those final structures.
An immunoconjugate of a murine monoclonal antibody CYT-099 (B72.3), with specificity for tumor-associated glycoprotein-72 (TAG-72), a human pancarcinoma antigen, chemically-linked to a linker-chelator molecule, glycyl-tyrosyl-(N,N-diethylenetriaminepentaacetic acid)-lysine hydrochloride (GYK-DTPA-HCl). This agent is reacted in the nuclear pharmacy with Indium-111 radioisotope to form the active radioimmune conjugate, which is injected for radioimaging of tumors expressing TAG-72.
Adjuvant used in chemotherapy that acts by stimulating the immune system.
A natural or synthetic substance, such as a drug, vitamin, hormone, plant product or food supplement, that may reduce the risk of developing or recurrence of tumor formation. Chemopreventive agent may work at different stages and may inhibit the initiation, promotion, transformation, and/or progression of the malignant process.
An agent applied topically that inhibits the maturation, growth or spread of tumor cells.
The psychological, emotional, and sexual abuse of a child, typically by a parent, stepparent, or parent surrogate.
A congenital mesoblastic nephroma characterized by increased cellularity, sheet-like proliferation of fibroblastic cells, and increased mitotic activity. Necrotic changes are commonly present.
A congenital mesoblastic nephroma characterized by the presence of interlacing fascicles of fibroblastic cells, low mitotic activity, and collagen formation.
A second generation murine monoclonal antibody with high affinity for the tumor-associated glycoprotein (TAG)-72, a human pancarcinoma antigen. Chimeric humanized CC49 (CHCC49) antibodies are generated through replacing the murine immunoglobulin (Ig) constant regions with the human constant regions of the heavy and light Ig chains, as well as through grafting CC49 hypervariable regions onto frameworks of the variable light (VL) and variable heavy (VH) regions of human monoclonal antibodies LEN and 21/28'CL, respectively. Utilizing CHCC49 antibodies avoid anti-mouse immune response in human, which occured with the use of mouse CC49 antibody, but still exhibit the same affinity for human TAG-72 antigen, thereby resulting in strong radioimaging activity when linked to a radioisotope.
A process that involves the binding of calcium or an extracellular ligand to a calcium channel. These interactions are involved in restoring the electrochemical potential of the resting membrane.
An alkylating antineoplastic agent no longer used in the United States, because it induces chromosomal aberration and causes cancer. (NCI)
A pyrimidine derivative with antitumor activity. Chlorodihydropyrimidine competitively and reversibly inhibits dihydropyrimidine dehydrogenase, a rate-limiting enzyme in the catabolism of fluoropyrimidines thereby blocking the degradation of the fluoropyrimidines.
Chlorzoxazone Acetaminophen is a combination of muscle relaxant (Chlorzoxazone) and anti-inflammatory analgesic (Acetaminophen) indicated in acute painful musculoskeletal diseases. The active principal metabolite of phenacetin, Acetaminophen appears to inhibit prostaglandin biosynthesis in the central nervous system and less in peripheral tissues. With mild sedative properties, centrally acting Chlorzoxazone inhibits muscle spasm at the spinal cord and subcortical levels of the brain. (NCI04)
An intrahepatic cholangiocarcinoma that arises from the canals of Hering.
Glycosaminoglycans (GAGs) are linear polysaccharide chains consisting of repeating disaccharide units and form proteoglycans by covalently attaching to their core proteins. Chondroitin sulfate (CS) is a glycosaminoglycan with the disaccharide unit GalNAc(b1-4)GlcA(b1-3), modified with ester-linked sulfate at certain positions. Dermatan sulfate (DS) is a modified form of CS, in which a portion of D-glucuronate residues is epimerized to L-iduronates. CS and DS are linked to serine residues in core proteins via a linkage tetrasaccharide formed by the transfer of xylose and three more residues. The assembly process of CS is initiated by the transfer of N-acetylgalactosamine to the linkage tetrasaccharide. The polymerization step is catalyzed by bifunctional enzymes (chondroitin synthases) that have both b-3 glucuronosyltransferase and b1-4 N-acetylgalactosaminyltransferase activities. Chondroitin polymerization also requires the action of the chondroitin polymerizing factor. Sulfation of chondroitin in vertebrates is a complex process, with multiple sulfotransferases involved in 4-O sulfation and 6-O sulfation of N-acetylgalactosamine residues. Additional enzymes exist for epimerization of glucuronic acid to iduronic acid in DS, sulfation at the C-2 position of the uronic acids, and other patterns of sulfation found in unusual species of chondroitin.
RXR and RAR are nuclear receptors that bind either all trans retinoic (tRA) or 9cis retinoic acid (9cisRA). In the absence of ligand corepressors with histone deacetylase activity are bound to the RAR/RXR heterodimer and suppress transcription. Once they bind retinoic acid a conformational change in the receptors cause the dissociation of the corepressors and the binding of coactivators with histone acetylase activity. Following ligand binding by the heterodimer the receptors and proteins in the basal transcription machinery (like TBP and TAF135) are degraded by the proteasome. (This definition may be outdated - see the DesignNote.)
An aberration in which an extra chromosome or a chromosomal segment is made.
A chromosomal rearrangement in which a segment a segment of DNA is added internally to a chromosome.
Loss of an entire chromosome or chromosome arm.
Primary myelofibrosis characterized by reticulin or collagen fibrosis in the bone marrow. The bone marrow is usually normocellular or hypocellular. Myeloblasts account for less than 10% of the bone marrow cells. Atypical megakaryocytes are present.
Primary myelofibrosis characterized by bone marrow hypercellularity and the presence of atypical megakaryocytes. There is no increase in the percentage of myeloblasts and no significant increase in reticulin or collagen fibrosis in the bone marrow.
The citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form of acetate, derived from glycolysis and pyruvate oxidation of carbohydrates and from beta oxidation of fatty acids. The two-carbon acetyl group in acetyl-CoA is transferred to the four-carbon compound of oxaloacetate to form the six-carbon compound of citrate. In a series of reactions two carbons in citrate are oxidized to CO2 and the reaction pathway supplies NADH for use in the oxidative phosphorylation and other metabolic processes. The pathway also supplies important precursor metabolites including 2-oxoglutarate. At the end of the cycle the remaining four-carbon part is transformed back to oxaloacetate. According to the genome sequence data, many organisms seem to lack genes for the full cycle, but contain genes for specific segments.
A morphologic variant of basal cell carcinoma characterized by the presence of clear cells.
The process by which a normal cell accumulates genetic changes that allow it to become a tumor-causing cell and furthers its development to more malignant states.
Multiplication or reproduction by cell division of a population of identical cells descended from a single progenitor. In immunology, may refer to the clonal proliferation of cells responsive to a specific antigen as part of an immune response. (NCI)
A DNA sequence rearrangement that results in the creation of a novel immunoglobulin. This process occurs during the differentiation of B-lymphocytes, such that individual B-cell progenitors, and their descendents, express an identical antibody molecule.
A molecular abnormality indicating rearrangement of the IGH gene in clonal populations of either lymphocytes or lymphocyte lineage neoplastic cells.
During HIV infection, the virus may evolve and become able to use alternative cell surface factors as receptors for cell attachment and entry. This can increase the tissue range of infection or allow the virus to overcome drugs which block virus entry.
A T cell that has been coated with monoclonal antibodies to enhance its ability to kill tumor cells.
A morphologic finding indicating the presence of dense stromal fibrosis in a tissue sample.
A combination of two or more anti-infective agents in a single product to increase the products effectiveness.
A medication containing two or more active ingredients acting in a synergistic or potentiating manner to treat a disease state.
A neuroblastic tumor characterized by the presence of a ganglioneuroblastoma component and the formation of Schwannian stroma which constitutes more than fifty-percent of the tumor volume.
A neuroblastic tumor characterized by the presence of a ganglioneuroblastoma component and the formation of Schwannian stroma which is the predominant component of the tumor volume.
A immunoconjugate comprised of a monoclonal antibody directed against the pancarcinoma antigen TAG-72.conjugated to PA-DOTA, a bifunctional chelant. TAG-72 is a protein/sugar complex found on the surface of many cancer cells, including breast, colon, and pancreatic cancer cells. (NCI04)
The body gets energy through the oxidation of food such as glucose and fatty acids. The chemical energy contained in these foods is extracted and converted until it reaches a common form, the high-energy phosphate bonds of ATP. The hydrolysis of ATP is highly favorable and is coupled to a variety of energetically unfavorable processes to drive them forward. Most of the energy of glucose or fatty acids is extracted through oxidation to produce the reduced high-energy electron carriers NADH and FADH2. From there, the energy is transferred next to the electron transport system associated with the mitochondrial inner membrane. This chain includes a series of protein complexes and non-membrane cofactors that transfer the electrons from NADH and FADH2 in a series of redox reactions from carrier to carrier. Oxygen is the final electron acceptor at the end of the chain, resulting in the production of water. The oxygen we breathe, and which is transported by hemoglobin in the blood to all of the tissues, serves this purpose and allows electron transport to occur. As the electrons pass through the chain, they transfer their energy to the complexes, which use the energy to pump protons out of the mitochondrial matrix, creating a proton gradient across the inner mitochondrial membrane. The chemical energy that started with glucose, and was transferred to NADH and FADH2, is then converted to the energy of a concentration gradient. The inner mitochondrial membrane is impermeable to protons on its own, so the energy of the proton gradient is stable, waiting to be recaptured. The energy is recaptured by ATP synthase in the inner mitochondrial membrane. This enzyme allows protons to flow back down their concentration gradient across the membrane, and in the process uses the energy of the gradient to drive ATP synthesis. The movement of the electrons through electron transport, the proton gradient and ATP synthesis are all coupled processes that require each other to occur. The cell does not store energy as ATP, but only has enough ATP on hand for its immediate energy needs. If electron transport ceases or is inhibited, then ATP synthesis also rapidly halts. This regulation ensures that ATP production closely matches the needs of the cell. Glycolysis and the Krebs cycle are also closely linked to the energy needs of the cell. The abundance of ATP, NADH and pathway intermediates regulates key steps in these pathways so that they are activated when energy is required to feed the electron transport system and they are inhibited when not needed to save metabolic energy. If oxygen is absent, electron transport and the Krebs cycle rapidly halt, leaving glycolysis and fermentation as the main means of energy production. During aerobic exercise, the rapid consumption of ATP leads to use of the proton gradient to make more ATP, increased electron transport to regenerate the proton gradient, increased oxygen consumption, and increased activity of the Krebs cycle and glycolysis to supply high energy electrons to drive electron transport. Uncoupling agents allow protons to flow across the mitochondrial membrane without producing ATP. The chemical compound dinitrophenol (DNP), for example, can transport protons across the inner mitochondrial membrane without ATP synthase. In the presence of dinitrophenol, energy is consumed to pump protons out of mitochondria, but this energy is not recaptured in chemical form in ATP. Instead, this energy is released as heat. Dinitrophenol was once used as diet remedy to lose weight without exercise or diet, but this compound is a metabolic poison and resulted in deaths in when purposefully given to humans. Proteins also can act as uncoupling agents in the mitochondria. A mitochondrial uncoupling protein is found in brown adipose tissue. An increase in the activity of uncoupling proteins increases heat production by allowing protons to flow down their gradient without making ATP and may serve as protection against cold, as well as a potential means of obesity control. (This definition may be outdated - see the DesignNote.)
Any mutation that results in the embryonic death of the organism carrying the mutation.
Simple or complex endometrial hyperplasia characterized by the absence of epithelial atypia.
An adenocarcinoma that arises from the endometrium and is characterized by the presence of both type I and type II endometrial adenocarcinoma components. The minor component constitutes at least 5% of the entire tumor.
A precursor of endometrial serous adenocarcinoma characterized by the replacement of the normal endometrial cells by malignant glandular cells that resemble the malignant cells of invasive serous adenocarcinoma. The endometrial neoplastic process is non-invasive. It may coexist with invasive endometrial adenocarcinoma or can be associated with metastases outside the uterus, in the absence of invasive endometrial carcinoma.
A primary carcinoma of the endometrium that is similar to the small cell carcinoma of the lung, histologically.
A rare primary carcinoma of the endometrium characterized by the presence of malignant epithelial cells resembling urothelial transitional cells. The malignant transitional cells constitute at least 90% of the tumor cells.
A primary carcinoma of the endometrium characterized by the presence of malignant cells that lack evidence of differentiation.
An angiogenesis inhibitor that acts by blocking the action of endothelial integrins. An endothelial-specific integrin/survival signaling inhibitor binds to and blocks the activity of endothelial-specific integrins, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis.
An angiogenesis inhibitor that acts by inhibiting the growth, migration, and proliferation of endothelial cells and/or induces endothelial cell apoptosis.
A group of agents that bind to the endothelin-1 receptor (primarily endothelin-A receptor, or ET-A), thereby inhibiting tumor cell proliferation and tumor associated angiogenesis. (NCI04)
An enediyne antineoplastic antibiotic isolated from Streptomyces bacterial species or derived synthetically. After cycloaromatization, the enediyne core of these antibiotics is converted to a benzene diradical intermediate that removes hydrogens from deoxyriboses along the minor groove of DNA, resulting in single- and double-strand breaks and apoptosis.
Any process by which signals are passed between two distinct cell types over a distance, typically through the circulatory system. This process is employed in most hormone-receptor communication, and is involved in metabolism, immune response, sexual development, behavior, nervous system function, regulation of mood and circadian rhythms, as well as other processes.
Synthetic enzyme or mixture of enzymes used to replace or supplement enzymes to treat enzyme deficiency or to promote healthy body functions.
Through physical or functional dissociation, Enzyme Uncoupling involves alteration (typically disruption) of activity of a physically or functionally coordinated biological complex that possesses catalytic activity.
A cyclic ether compound with a three-atom ring containing oxygen linked to two carbons. These rings are highly stressed and more reactive than a typical acyclic ether.
The neuregulins comprise a subfamily of at least four epidermal growth factor (EGF)-like growth factors that influence a variety of cellular events, including proliferation, differentiation, migration, survival, and fate. The most thoroughly examined neuregulin, neu differentiation factor NDF (AKA: neuregulin-1; NRG1; also heregulin, glial growth factor, or acetylcholine receptor-inducing activity), has been shown to play essential roles in the development of cardiac and neural tissues and also has been shown to play a role in the postsynaptic development of the neuromuscular junction. The neuregulins bind to ErbB3 or ErbB4 and can activate the ErbB2 receptor through a heterodimerization mechanism. Heterodimers of ErbB3 and ErbB2, which has no direct ligand, are potent in causing cell transformation. Controlled levels of signaling through ErbB and other growth factor receptors are maintained by keeping a relatively limited amount of receptors at the cell surface. Receptor overexpression can lead to disease states such as the genesis or progression of tumors. Hence, mechanisms must exist for localizing and maintaining a precise concentration of growth factor receptors at the site of signal reception. ErbB2, ErbB3, and ErbB4 are somewhat unique among studied receptor tyrosine kinases in that they exhibit impaired ligand-induced internalization, down-regulation, and degradation. In fact, the rate of degradation is dependent on factors that appear to act independent of ligand binding. Nrdp-1 (Neuregulin receptor degradation protein-1) is one such protein. Ndrp-1 is an E3 ubiquitin ligase that tags ErbB3 for degradation in non-lysosomal compartments. The cycling of ErbB1 is similar to that of EGF receptor and is included for contrast. (This definition may be outdated - see the DesignNote.)
Erythropoietin (Epo) is most commonly known as the cytokine secreted by the kidneys that stimulates red blood cell production and is used as a drug for the treatment of anemias. Epo is also secreted in the brain in response to hypoxia, such as ischemic stroke. Epo production in the brain is stimulated by the hypoxia-inducible transcription factor HIF-1 (see HIF pathway). Administration of Epo to the brain in rodents before hypoxic stress or other neuronal stresses is neuroprotective, preventing neuronal apoptosis. The erythropoietin receptor (EpoR) is known to associate with JAK kinases that phosphorylate and activate the STAT family of transcription factors. The neuroprotection by Epo involves cross-talk between Epo receptor and anti-apoptotic pathways through activation of NF-kB by the JAK2 kinase. Epo stimulates JAK2 phosphorylation of I-kB, releasing NF-kB to translocate into the nucleus and activate transcription of neuroprotective genes. Neuroprotective genes activated by NF-kB include the anti-oxidant enzyme manganese superoxide dismutase and calbindin-D28k. The erythropoietin receptor is also essential for proper brain development in mice. The absence of EpoR causes high levels of neuronal apoptosis in the developing mouse brain, further confirming the important role of Epo as a neuroprotective agent. (This definition may be outdated - see the DesignNote.)
Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known. The methylation activity of CARM1 modulates the activity of specific transcriptional regulators. CARM1 acts as a coactivator for the myogenic transcription factor Mef2c, and is necessary for normal muscle cell differentiation. The estrogen receptor is another transcription factor that uses CARM1 as one of several coactivators, acting synergistically with CBP through the Grip1 member of the p160 family of coactivators. The interaction of estrogen receptor with various ligand-dependent coactivators may produce the tissue selective response of some estrogen receptor ligands like tamoxifen. (This definition may be outdated - see the DesignNote.)
The chloride salt of ethidium (a fluorochrome), Ethidium Chloride intercalates within double-stranded nucleic acids, particularly DNA. In molecular biology, the bromide salt of ethidium is used to detect and visualize DNA after electrophoresis or in cytochemical preparations. In veterinary pharmacology, it is used as a trypanosomicide. Ethidium bromide and chloride are toxic substances and potent noncompetitive antagonists of the nicotinic acetylcholine receptor. (NCI04)
Disease that cannot be measured directly by the size of the tumor but can be evaluated by other methods specific to a particular clinical trial.
Environmental factors considered as variables in disease incident, transmission, and control.
Any adverse event associated with a medical product or procedure, whose nature and severity have been previously observed, identified in nature, severity, or frequency, and documented in the investigator brochure, investigational plan, protocol, current consent form, scientific publication, or in other relevant and reliable document. The old term Side Effect is retired and should not be used.
Activation of the MAPK kinase pathway has been identified as a mechanism that integrins use to regulate gene expression, leading to cell shape changes during cell spreading or migration. Epithelial cells respond to extracellular matrix (ECM) causing integrin-mediated FAK phosphorylation; this, in turn, phosphorylates the surrounding proteins (paxillin, Fyn/shc, and src) and leads to signal amplification. FAK also binds PI-3 kinase and acts upstream in the MAP kinase pathway. When MAP kinase or PI-3 kinase is inhibited, actin reorganization is blocked. Src phosphorylates p190RhoGAP, inactivating its GAP function and allowing RhoGTP to stay active longer, promoting further signal amplification. Activated RhoGTP binds to downstream kinases such as Rho-associated coiled coil-containing protein kinase (p160ROCK) and p140 diaphanous (p140Dia) to increase actin polymerization and contraction. Actin reorganization assists integrin clustering, allowing more ECM binding that increase FAK phosphorylation and other signal transduction events. (This definition may be outdated - see the DesignNote.)
A finding indicating the presence of disease beyond the skin.
A clinical finding that refers to the spread or absence of lymphoid cancer in anatomic sites or systems other than the original lymph node site of growth.
A naturally occurring 9-residue peptide of fibroblast growth factor 5 (FGF-5). Recognized by tumor infiltrating cytotoxic T lymphocytes originally isolated from a renal cell carcinoma that overexpressed FGF-5, FGF-5:172-176/217-220 peptide activates various cytotoxic CD8 lymphocytes in an HLA-restricted manner. Overexpressed in several cancer cell lines, FGF-5 is a tumor-associated antigen that may be useful in cancer immunotherapy. (NCI04)
A molecular genetic abnormality indicating the presence of multiple copies of the FGFR1 gene.
A change in the nucleotide sequence of the FGFR3 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the FGFR2 gene.
A fusion protein of clotting factor VII with the Fc portion of an IgG1 antibody. In the lab it can target to the blood vessels of solid tumors and initiate an immune response that results in the destruction of the blood vessel and death of the tumor.
A rare, benign, asymptomatic neoplasm that arises from the fallopian tube. The majority of cases are incidental findings during operation for an unrelated gynecologic disorder. The tumors are round and solitary and contain connective tissue and papillary or tubular structures lined by serous-type epithelium.
A benign neoplasm that arises from the fallopian tube and originates from mesothelial cells. It is characterized by the presence of gland-like structures that are lined by flat or cuboidal cells. It is usually discovered as an incidental finding.
A rare, benign, asymptomatic neoplasm that arises from the fallopian tube. The tumors are round and solitary and contain connective tissue and cystic structures lined by serous-type epithelium. The majority of cases are incidental findings during operation for an unrelated gynecologic disorder.
An adenomatous polyp that arises from the interstitial portion of the fallopian tube and is characterized by the presence of endometrial epithelium. It may obstruct the lumen of the fallopian tube and result in infertility or tubal pregnancy.
A benign, borderline, or malignant epithelial tumor of the fallopian tube that is characterized by the presence of glands and/or cysts lined by neoplastic cells that resemble endometrial cells.
A rare germ cell tumor that affects the fallopian tube. The vast majority of cases are teratomas.
A benign smooth muscle neoplasm arising from the fallopian tube. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
An aggressive malignant smooth muscle neoplasm, arising from the fallopian tube. It is characterized by a proliferation of neoplastic spindle cells.
A carcinosarcoma that arises from the fallopian tube. It usually affects postmenopausal women and presents with abdominal pain, abdominal distension or genital bleeding. The prognosis is usually poor.
A rare metaplastic lesion that arises from the fallopian tube. It is characterized by the presence of an intraluminal papillary proliferation composed of atypical epithelial cells with abundant eosinophilic cytoplasm. In the vast majority of cases, it is an incidental finding during microscopic examination of a fallopian tube in the postpartum period.
An extremely rare adenocarcinoma that arises from the fallopian tube. It is characterized by the presence of neoplastic epithelial cells that contain intracytoplasmic mucin. The cases that have been reported are predominantly in situ mucinous adenocarcinomas.
A rare borderline or malignant epithelial tumor of the fallopian tube characterized by the presence of neoplastic epithelial cells that contain intracytoplasmic mucin and may resemble the epithelial cells of the endocervix or gastrointestinal tract.
An extremely rare malignant neoplasm that arises from the fallopian tube and is characterized by the presence of a benign epithelial component and a sarcomatous component.
A benign epithelial neoplasm that arises from the fallopian tube. It is characterized by the presence of fibrovascular stalks lined by serous epithelial cells.
A serous adenocarcinoma that arises from the fallopian tube. It is usually a high grade invasive adenocarcinoma.
A benign, borderline, or malignant epithelial tumor of the fallopian tube characterized by the presence of neoplastic serous epithelial cells.
A benign or malignant mesenchymal neoplasm of the fallopian tube. Representative examples include leiomyoma and leiomyosarcoma.
A teratoma that arises from the fallopian tube. It is a rare tumor, often found incidentally.
A rare transitional cell carcinoma that arises from the fallopian tube.
Any substance that inhibits protein farnesyltransferase, an enzyme that catalyzes the transfer of a farnesyl moiety from farnesyl pyrophosphate to a cysteine. Protein farnesyltransferase is involved in Ras-mediated post-translational modification. Inhibition of protein farnesyltransferase may inhibit the oncogenic activity of Ras.
Farnesylation Inhibition involves interference with, or restraint of, enzymatic activities involved in covalent addition of farnesyl group(s) (three isoprene units) to polypeptide chains that contain the C terminal motif CAAX after assembly from messenger RNA at the ribosome.
Receptors in the TNF receptor family are associated with the induction of apoptosis, as well as inflammatory signaling. The Fas receptor (CD95) mediates apoptotic signaling by Fas-ligand expressed on the surface of other cells. The Fas-FasL interaction plays an important role in the immune system and lack of this system leads to autoimmunity, indicating that Fas-mediated apoptosis removes self-reactive lymphocytes. Fas signaling is also involved in immune surveillance to remove transformed cells and virus infected cells. Binding of FAS to oligomerized FasL on another cell activates apoptotic signaling through a cytoplasmic domain termed the death domain that interacts with signaling adaptors including FAF, FADD and DAX to activate the caspase proteolytic cascade. Caspase-8 and caspase-10 are first activated and then cleave and activate downstream caspases, and a variety of cellular substrates, leading to cell death. Caspases cleave nuclear lamins, causing the nucleus to break down and lose its normal structure. They also cleave DFF, inducing cleavage and degradation of the genome. Other caspase substrates are involved in cytoskeletal structure, cell cycle regulation and signaling pathways. Activation of JNK kinase, activation of Jun, and production of ceramide may also play roles in Fas-mediated apoptosis. Activation of Fas-mediated apoptosis is opposed by I-FLICE and FAP. Viruses and tumors may escape immune surveillance in part through suppression of Fas-mediated apoptosis. (This definition may be outdated - see the DesignNote.)
The Fc Epsilon Receptor 1 signaling pathway in mast cells uses multiple core signal paths to achieve its necessary ends. Through the BTK protein and PKC Mast cells are able to degranulate, through the PKC and MAPK paths the cells are able to alter cytokine expression and arachidonic acid release. (This definition may be outdated - see the DesignNote.)
A substance derived from folic acid that acts as a precursor or cofactor of enzymes and inhibitors involved in biosynthesis of amino acids, proteins and nucleic acid components.
Formation of Apurinic Site involves the creation of an apurinic site as a result of the loss of a purine residue from DNA. Purine residues are especially vulnerable to cleavage of the N-glycosylic bond between the purine residue and sugar moiety of the nucleotide, leaving in DNA a nucleotide position with no base attached.
Formation of Apyrimidine Site involves the creation of an apyrimidinic site as a result of the loss of a pyrimidine residue from DNA.
Formation of Bistrand Abasic Site involves the creation of an apurinic or apyrimidinic site on one strand with a loss of the opposing purine or pyrimidine residue on the other DNA strand.
Neutrophils respond to bacterial infection by releasing reactive oxygen species that kill bacteria and by expressing chemokines that attract other immune cells to the site of infection. The multisubunit enzyme NADPH oxidase, expressed by neutrophils, produces reactive oxygen species that are rapidly released in what is known as the respiratory burst. Activity of the NADPH oxidase is induced by fMLP receptor ligands, formylated peptides from bacteria. The fMLP receptor is a G-protein coupled receptor, FPR-1, that activates Map kinase pathways and phospholipase C. Phospholipase C activation releases IP3 and calcium, activating protein kinase C and also activating the transcription factor NFAT, which contributes to activation of chemokine genes. One of the components of the NADPH oxidase is p47phox. PKC activation phosphorylates p47phox to activate NADPH oxidase activity. Activation of Map kinase cascades leads to Erk1/Erk2 dependent p47phox phosphorylation as well as activation of the Elk-1 transcription factor and chemokine gene expression. Inhibition of p38 did not affect p47phox phosphorylation, indicating that p38 is not involved in Erk1/2 activation of the NADPH oxidase. Inhibition of p38 did inhibit NADPH oxidase though, indicating that other pathways contribute to activation of this enzyme. (This definition may be outdated - see the DesignNote.)
A peptide derived from the tumor suppressor protein Von Hippel-Lindau (VHL). This peptide, sequence: MEAGRPRPCCAR, was constructed based on a frameshift mutation of one of the VHL gene products; the more abundant protein VHLp18(MEA) (where MEA stands for three amino acids, Met-Glu-Ala). Vaccination with FrSh61(MEA)VHL33 peptide may stimulate a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing this VHL mutant protein.
Any subcellular metabolic process in which at least one of the participants has one or more electrons that singly occupy an electron orbital. Free radical processes may promote or prevent damage to tissues in which they arise.
Free Radical Formation involves production in normal or pathological processes of chemically unstable, short half-life and highly reactive molecules carrying at least one unpaired or 'free' electron in the outermost electron shell. Appropriating electron(s) from a nearby molecule and damaging that molecule by altering the electron number in its outermost electron shell, Free Radicals produce tissue damage.
Oxidative stress is one factor that can trigger programmed cell death. Activated neutrophils responding to inflammatory stimulation produce reactive oxygen species like superoxide free radicals to kill invading bacteria, but these reactive oxygen species can also attack endothelial cells lining the vascular wall and trigger apoptosis. Endothelial cells also produce reactive oxygen species inside the cell that can contribute to oxidative stress and apoptosis, such as during reperfusion injury following ischemia. Superoxide dismutase (SOD) converts highly reactive and damaging superoxide free radicals to peroxides that are less reactive than superoxide but stimulate apoptosis. The glutathione (GSH) peptide reducing agent removes toxic metabolites and repairs damage created by reactive oxygen species. Glutathione peroxidase (GPx), for example, removes peroxides using glutathione as a reducing agent, and glutathione reductase (GSR) regenerates reduced glutathione. Inside the endothelial cell peroxide can be converted to hydroxyl ions in the presence of iron. Peroxides and hydroxyl radicals activate NF-kB and activate expression of inflammatory genes including adhesion molecules, TNF and IL-8. The apoptotic response of endothelial cells to oxidative stress may be involved in the development and progression of atherosclerosis. (This definition may be outdated - see the DesignNote.)
Free Radical Binding involves temporary interaction with chemically unstable and highly reactive molecules (free radicals) having an unsatisfied electron valence pair. Agents of tissue damage through exposure to radiation, environment chemicals, and aging, reactive free radicals stabilize themselves by appropriating an electron from a nearby molecule and damaging that molecule by altering the electron number in its outermost electron shell.
Free Radical Suppression involves interference with, or restraint of, production in normal or pathological processes of chemically unstable, short half-life and highly reactive molecules carrying at least one unpaired or 'free' electron in the outermost electron shell. Appropriating electron(s) from a nearby molecule and damaging that molecule by altering the electron number in its outermost electron shell, Free Radicals produce tissue damage.
A receptor-targeted complex comprised of a truncated toxin fused to a hormone, growth factor, or immunologic agent (i.e. antibody) that binds to the tumor cell allowing the toxin to kill the cell following internalization.
G-aS-coupled receptors stimulate adenylyl cyclase (AC), which synthesizes cAMP from ATP. In contrast Gai-coupled receptors inhibit AC and so reduce cAMP formation. The bg subunits from Gai and other G proteins are able to activate the MAP kinase pathways and PLCb. GPCRs coupled to the Gaq family of G proteins stimulate PLCb, which cleaves membrane phospholipids to produce IP3, which mobilizes intracellular calcium, and DAG, which activates PKC. Second messenger pathways then activate a range of effector systems to change cell behavior; in many cases this includes the regulation of gene transcription. (This definition may be outdated - see the DesignNote.)
G1-S Arrest consists of cellular biochemical mechanisms, responsive to diverse governing conditions (DNA damage, contact inhibition, growth factors, etc.), that control cellular commitment at the G1 restriction point to DNA replication and the proliferative cycle. G1 to S is controlled by de/phosphorylated cyclin/CDK complexes. During G1, cycD/CDK phosphorylation of Rb/HDAC repressor permits E2F/DP1 transcription of genes that promote the G1/S switch and DNA replication. p53 induces p21 inhibition of cycD/CDK; Mdm2 inhibits p53/p21. TGF-b induces p15 inhibition of cycD/CDK. cAMP induces p27 inhibition of cycD/CDK. GSK3b induction of cycD degradation, and INK4, Kip, and Cdc25A regulate cycD/CDK activity.
Processes that mark, promote, and sustain the commencement of, and commitment to continue, cellular processes involved in the S phase of the cell cycle, such as replication.
G1 Arrest consists of cellular biochemical mechanisms, responsive to diverse governing conditions (DNA damage, contact inhibition, growth factors, etc.), that control cellular progress through the G1 phase of the cell cycle. G1 progress is controlled by de/phosphorylated cyclin/CDK complexes. During G1, cycD/CDK phosphorylation of Rb/HDAC repressor permits E2F/DP1 transcription of genes that promote the G1/S switch and DNA replication. p53 induces p21 inhibition of cycD/CDK; Mdm2 inhibits p53/p21. TGF-b induces p15 inhibition of cycD/CDK. cAMP induces p27 inhibition of cycD/CDK. GSK3b induction of cycD degradation, and INK4, Kip, and Cdc25A regulate cycD/CDK activity.
G2/M Arrest consists of cellular biochemical mechanisms, responsive to diverse conditions, that control cellular transition from the G2 to M phase of the cell cycle. Cdc2/cycB regulates this transition. During G2, Cdc2 is inactivated by Wee1 and Mt1 kinases. Activation of Cdc25 phosphatase activates Cdc2. If genome damage has occurred, activated DNA-PK/ATM/ATR kinases inactivate Cdc2/cycB by two channels. First, Cdc25 is inactivated by CHK kinases. Second, phosphorylated p53 dissociates from MDM2, is acetylated by p300/PCAF, binds DNA, and activates transcription of genes that inhibit Cdc2/cyclin (14-3-3s, GADD45, and p21Cip1).
Progression from G2 phase to M phase of the standard mitotic cell cycle. (From Gene Ontology)
A process that involves the binding of gamma-aminobutyric acid to a GABA A receptor. These interactions are involved in inhibition of neurotransmission.
A process that involves the non-covalent binding of gamma-amino butyric acid to the gamma-amino butyric acid type b receptor. This interaction is involved in the stimulation of Gs protein-dependent signaling, which regulates potassium ion flux, neuronal action potentials, voltage-dependent calcium channel activity and neurotransmitter release.
Gamma-amino butyric acid (GABA) is an inhibitory neurotransmitter that acts at synapses through binding to ligand-gated ion channels, the GABA receptors. Clustering of the GABA-A receptor chloride channel alters receptor pharmacology on the cell surface and reduced clustering of the GABA receptor is associated with anxiety. GABA-A interacts with several proteins that modulate its clustering, endocytosis, and recycling or degradation. Plic-1 is a ubiquitin-like protein that binds to GABA-A receptors and causes them to accumulate at inhibitory synapses. Gephyrin interacts with the cytoplasmic domain of GABA-A, and with microtubules, bringing receptors together in plasma microdomains. Curiously, Gephyrin appears to be a bifunctional protein, with a domain involved in molybdenum metabolism. Another protein interacting with the GABA-A receptor is GABARAP, a microtubule-associated protein. Anchoring of the GABA-A receptor to GABARAP helps to cluster the receptor at the synaptic termini and to mediate fast synaptic transmission. GABARAP may mediate interaction of gephyrin with the GABA-A receptor and gephyrin may stabilize clusters by forming multimeric structures. GABARAP and gephyrin may play more of a role in receptor sorting and transport to the cell surface than in anchoring to the cytoplasm, since at inhibitory synapses GABARAP appears to associate with transport vesicles rather than the cell surface. The association of GABARAP with NSF (N-ethyl maleimide sensitive factor), a protein involved in intracellular vesicle transport, supports this hypothesis. (This definition may be outdated - see the DesignNote.)
GD2 Binding Interaction involves non-covalent attachment of a molecule through intermolecular physical forces of attraction to a widely expressed cell surface ganglioside antigen, GD2.
GD3 Binding Interaction involves non-covalent attachment of a molecule through intermolecular physical forces of attraction to a cell surface liposaccharide disialoganglioside, GD3.
A mixed-backbone antisense oligonucleotide that is complementary to a pro-angiogenic vascular endothelial growth factor (VEGF) mRNA sequence. Because of its antiangiogenic properties, GEM 220 has been studied as a potential antineoplastic agent. (NCI04)
DNA that encodes granulocyte-macrophage colony stimulating factor (GM-CSF). GM-CSF enhances the host immune response to poorly immunogenic tumors, possibly by activating T-cell and macrophage anti-tumor responses, and, so, decreasing tumor growth. (NCI04)
Expression vectors containing the complementary DNA (cDNA) of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) coated onto gold particles. A protein cytokine secreted by T-cells and macrophages following cell activation by antigens or mitogens, GM-CSF is indispensable for the growth and development of granulocyte and macrophage progenitor cells. Subsequently, GM-CSF has been shown to activate and stimulate proliferation of mature macrophages and lymphocytes. (NCI04)
Homologous desensitization of GPCRs results from the binding of b-arrestins (b-arr) to agonist -occupied receptors following phosphorylation of the receptor by GRKs. b-arrestin binding sterically precludes coupling between the receptor and heterotrimeric G proteins, leading to termination of signaling by G proteins effectors. Receptor-bound b-arrestins also act as adapter proteins, binding to components of the clathrin endocytic machinery including clathrin, b2-adaptin (AP-2). Receptor sequestration reflects the dynamin (Dyn)-dependent endocytosis of GPCRs via clathrin-coated pits. Once internalized, GPCRs exhibit two distinct patterns of b-arrestin interaction. Class A GPCRs, for example the b2 adrenergic receptor, rapidly dissociate from b-arrestin upon internalization. These receptors are trafficked to an acidified endosomal compartment, wherein the ligand is dissociated and the receptor dephosphorylated by a GPCR-specific protein phosphatase PP2A isoform, and are subsequently recycled to the plasma membrane. Class B receptors, for example the angiotensin II AT1a receptor, form stable receptor-b-arrestin complexes. These receptors accumulate in endocytic vesicles and are either targeted for degradation or slowly recycled to the membrane via as yet poorly defined routes. (This definition may be outdated - see the DesignNote.)
A series of molecular signals that proceeds with an activated receptor promoting the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, or for basal GPCR signaling the pathway begins with the receptor activating its G protein in the absence of an agonist, and ends with regulation of a downstream cellular process, e.g. transcription. The pathway can start from the plasma membrane, Golgi or nuclear membrane (PMID:24568158 and PMID:16902576). [GOC:bf, GOC:mah, PMID:16902576, PMID:24568158, Wikipedia:G_protein-coupled_receptor]
Antineoplastic vaccine being developed against liver cancer. (NCI)
GVAX cancer vaccines are autologous cell vaccines comprised of tumor cells which have been irradiated and genetically modified to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), a hormone which plays a key role in stimulating the body's immune response to vaccines.
A cellular process that initiates with the binding of a G protein-associated transmembrane receptor to its cognate ligand,and results in a specific cellular response. This process is involved in signaling related to neurotranmission, immune responses, and cellular metabolism, differentiation and proliferation.
A chromosomal aberration where there are 3 copies of the long arm of chromosome 12. This aberration is associated with 12q duplication syndrome.
A cytogenetic abnormality that refers to the allelic gain of all or part of chromosome 17.
A cytogenetic abnormality that refers to the duplication of all or part of the long arm of chromosome 17.
A cytogenetic abnormality that refers to allelic gain within the chromosomal arm 1q.
A cytogenetic abnormality that refers to the duplication of all or part of the short arm of chromosome 2.
A chromosomal abnormality that refers to the gain of genetic material in the short arm of chromosome 6.
A chromosomal abnormality that refers to the gain of genetic material in the long arm of chromosome 8.
Any substance that inhibits glutamate-cysteine ligase (gamma-glutamylcysteine synthetase), an enzyme that catalyzes the ATP-dependent condensation of cysteine and glutamate to form the dipeptide gamma-glutamylcysteine, the rate-limiting step in the biosynthesis of glutathione. Since glutathione is critical in protecting cells against oxidative stress, its depletion results in free radical-induced apoptosis.
The HER4/erbB4 receptor tyrosine kinase is a member of the EGF1 receptor family. HER4 is a receptor for the neuregulins (NRGs), a family of growth and differentiation factors. HER4 can also bind and be activated by heparin-binding EGF growth factor, betacellulin, and epiregulin, members of the EGF family which, unlike the NRGs, are also ligands for the EGF receptor. HER4 mRNA is expressed in several tissues such as heart, brain, kidney, and skeletal muscle, suggesting that this receptor is involved in the development and maintenance of a variety of organs and cell types. It is likely that the control of expression and function of HER4 is important in normal development as well as in disease. (This definition may be outdated - see the DesignNote.)
A ganglioneuroblastoma characterized by the presence of neuroblastic cells in a Schwannian stroma, without the presence of hemorrhagic neuroblastic nodules.
A ganglioneuroblastoma characterized by the presence of neuroblastic cells in a Schwannian stroma, and the formation of hemorrhagic neuroblastic nodules.
A finding indicating the presence of large ganglion cells, neural cellular infiltrates and a stroma with Schwannian differentiation in a neoplastic tissue specimen.
Any substance that inhibits gastrointestinal lipase, an enzyme that is involved in the absorption of dietary lipids. Inhibition of gastrointestinal lipase causes a decrease in lipid absorption and a increase in fecal excretion.
A variation in or modification of the nucleic acid sequence of a gene that can alter its expression and may result in either a congenital disorder or the clinical presentation of a disease.
DNA constructs or co-administered agents used in gene therapy. Gene therapy constructs are used in delivery of genetic material into cells in order to permanently correct an inherited disease or an acquired disease such as cancer.
Agents used to transport genes or genetic material to a target tissue, including viruses, liposomal encapsulation, direct naked DNA injection, or molecular conjugates.
Generation of Antibody Diversity during B-lymphocyte development results from a cascade of temporally ordered random gene shuffling translocations by a recombinase that join any one of multiple alternative discrete V, D, and J (heavy chain) or V and J (light chain) antibody gene variable region DNA coding segments that produce in each B-lymphocyte an antibody with a unique antigen binding region composed of a heavy and a light protein chain. In addition, splicing inaccuracies or insertion of additional nucleotides at the segment junctions generate further junctional diversity and somatic hypermutation of V regions, as B-lymphocytes proliferate, create better fitting antigen-binding sites.
A rare malignant trophoblastic tumor that arises from the ovary as a result of ectopic ovarian pregnancy. There is no germ cell component present.
Metastasis that involves transfer of malignant cells via the cardiovascular system from one organ or part to another that is not directly connected with it.
Passage or transfer, as of a disease, by intravenous injection with shared drug paraphernalia from a donor intravenous drug abuser to a recipient intravenous drug abuser. (NCI)
An invasive breast carcinoma containing both ductal and lobular carcinomatous components.
An infiltrating bladder transitional cell carcinoma exhibiting micropapillary growth pattern. -- 2003
Molecules transmitting signals into cells often act through receptors in the plasma membrane that stimulate production of second messengers. When activated by a plasma membrane receptor, the enzyme phospholipase C (PLCg) hydrolyzes the membrane lipid phosphatidylinositol (PIP2) into the second messengers diacylglycerol (DAG) and IP3. IP3 releases calcium from intracellular stores into the cytoplasm where calcium alters many cellular activities, including activating protein kinase C. DAG also activates protein kinase C. Biologists often study signaling by artificially manipulating pathways using molecules like ionomycin and phorbol esters as research tools. Ionomycin is a molecule that carries calcium through the plasma membrane to increase the calcium concentration in the cytoplasm and activate protein kinase C without activating phospholipase C. Phorbol esters are molecules that mimic the action of DAG in the activation of protein kinase C, and were originally identified as tumor-promoting agents. The combination of ionomycin and phorbol esters is often used experimentally to study the effect of calcium and DAG signaling in cellular responses like T cell activation. (This definition may be outdated - see the DesignNote.)
Ion Exchanger Interaction consists of temporary non-covalent binding of a molecule through intermolecular physical forces of attraction with a membrane associated enzyme, or complex, involved in ATP-dependent transmembrane transport of a positively (cation) or negatively (anion) charged atom or radical against a concentration gradient resulting directly from the expenditure of energy.
Any cellular process involved in the translocation of charged macromolecules, solutes and solvents into or out of a cell.
Iron Chelation involves non-covalent coordination bonding between iron and an organic chemical, often as part of an enzyme or protein complex, as in the iron-binding porphyrin group of hemoglobin.
Iron Uptake Inhibition involves interference with, or restraint of, subcellular or molecular processes directly involved in the physical translocation from the extracellular to intracellular compartment of the metallic element Iron, which forms part of hemoglobin and enzyme systems essential for energy metabolism.
Isoprenylation Inhibition involves interference with, or restraint of, enzymatic activities involved in covalent addition of prenyl and multiprenyl residues to polypeptide chains after assembly from messenger RNA at the ribosome.
An orally available isoxazole urea with potential anti-tumor activity. In preclinical trials, N-(5-tert-butyl-3-isoxazolyl)-N-(4-(4-pyridinyl)oxyphenyl)urea inhibited raf kinase, an enzyme capable of reversing the phenotype of ras-transformed cells and blocking tumor growth. (NCI)
A granulosa cell tumor that involves both ovaries. It affects females in the first three decades of life.
A mutant form of the p21-ras protein transcribed from a mutant form of the oncogene K-ras. K-Ras is located in the plasma membrane and transduces growth and differentiation signals from activated receptors to protein kinases within the cell. K-RAS ASP-12 contains a mutation at codon 12 and may be used in cancer immunotherapy. (NCI04)
A synthetic form of the ras protein containing a point mutation at position 13 (glycine to asparagine). Vaccines using mutant K-ras proteins may be used in the immunotherapy of various cancers that express mutated K-ras proteins. (NCI04)
A synthetic form of the K-ras protein containing any one of a number of point mutations at position 12 which is normally occupied by glycine (GLY). Vaccines using mutant K-ras proteins may be used in the immunotherapy of various cancers that express mutated K-ras proteins. (NCI04)
A vaccine composed of tumor-associated antigen, mutant K-ras, which produces both a cytotoxic and helper T cell response to challenge tumor cells expressing the relevant K-ras oncogene. (NCI)
A synthetic form of the K-ras protein containing a point mutation at position 12 (glycine to valine). Vaccines using mutant K-ras proteins may be used in the immunotherapy of various cancers that express mutated K-ras proteins. (NCI04)
A chimeric lymphoma vaccine generated by combining the recipient's Ig idiotype (Id) protein with keyhole limpet hemocyanin (KLH), an immune stimulant, with potential antineoplastic activity. Vaccination with KLH-Lymphoma Ig Vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against lymphoma cells, resulting in decreased tumor growth. (NCI04)
A synthetic form of the K-ras protein containing a point mutation at position 12 (glycine to cysteine). Vaccines using mutant K-ras proteins may be used in the immunotherapy of various cancers that express mutated K-ras proteins. (NCI04)
A molecular genetic abnormality indicating the presence of multiple copies of the KRAS gene.
A variant of cervical squamous cell carcinoma characterized by the presence of keratin pearls. Intercellular bridges and cytoplasmic keratinization are usually present.
The tartrate salt form of ketanserin, a selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. Ketanserin is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.
Infiltration of the bone marrow by a malignant neoplasm.
A synthetic triarylimidazole with potential antineoplastic activity. As a Raf kinase inhibitor, L-779450 competes with ATP for binding to the Raf-1 and A-Raf catalytic sites, thus inhibiting their enzymatic activities and blocking various signal transduction pathways that depend on Raf-1 kinase (particularly the Ras-Raf-MEK-ERK cascade which is often up-regulated in neoplasms). (NCI04)
The amino acid methionine with selenium substituting for the sulphur moiety. Methionine is an essential amino acid in humans, whereas selenium is a free-radical scavenging anti-oxidant, essential for the protection of various tissues from the damages of lipid peroxidation. As a trace mineral that is toxic in high doses, selenium is a cofactor for glutathione peroxidase, an anti-oxidant enzyme that neutralizes hydrogen peroxide. L-Selenomethionine is considered a safe, efficacious form of selenium and is readily bioavailable. Selenium may be chemoprotective for certain cancers, particularly prostate cancer. (NCI04)
A molecular genetic abnormality indicating the presence of multiple copies of the MYCL gene.
Low-density lipoprotein (LDL) is a plasma lipoprotein particle whose lipid component includes cholesterol and triglycerides and is commonly referred to as bad cholesterol due to its role promoting atherogenic heart disease. LDL in the plasma originates from very-low density lipoprotein (vLDL) produced by the liver with the apoprotein B-100. vLDL is converted to LDL by the action of lipoprotein lipase, an enzyme that hydrolyzes triglycerides in vLDL, removing them from the vLDL particle and releasing free fatty acids. The removal of triglycerides from vLDL by lipoprotein lipase leaves a greater proportion of cholesterol, increasing the density of the particle and changing it to LDL. Atherogenic heart disease involves the formation of plaques in arterial walls that narrow the arterial passage, restricting blood flow and increasing the risk of occlusion of blood flow by a myocardial infarction. One of the first steps in the development of atherogenic heart disease is the passage of LDL out of the arterial lumen and into the arterial wall. Once there, the lipids in LDL are chemically modified and oxidized. Oxidized LDL stimulates inflammatory signaling by neighboring endothelial cells, releasing chemokines and cytokines such as M-CSF and MCP-1 and recruiting monocytes into the arterial wall. Once there, monocytes differentiate into macrophages and internalize modified LDL. These macrophages continue to internalize LDL, becoming enlarged and full of lipid. These cells accumulate in tissue and are transformed into foam cells, dying and forming part of the atherogenic plaque. Therapeutic intervention in atherogenic heart disease focuses first on lowering plasma LDL levels through diet and medication. The statins are drugs commonly used to block cholesterol production and increase the expression of the LDL receptor by the liver, removing LDL from circulation. Blocking LDL oxidation may also protect against atherogenesis, and may be the mechanism by which antioxidants such as vitamin E are proposed to reduce heart disease. Blocking the uptake of LDL by macrophages or inhibiting the inflammatory reaction against modified LDL may also offer routes to reduce the formation of atherogenic plaques. (This definition may be outdated - see the DesignNote.)
An orally-active synthetic aromatic retinoic acid agent with potential antineoplastic and chemopreventive activities. LGD 1550 selectively binds to all three retinoic acid receptors (RAR-alpha, RAR-beta, and RAR-gamma), resulting in alterations in the expression of genes responsible for cell differentiation and proliferation. This agent also acts as an inhibitor of activator protein 1 (AP-1), a protein that mediates trophic responses and malignant transformation. (NCI04)
LIS1 can bind to MT bundles; however, phospho-LIS1 binding to MT bundles is mediated through the distal zinc finger motif of CLIP-170. When the distal zinc finger motif of CLIP-170 is mutated, the phospho-LIS1 isoform can no longer bind to MT bundles. This can also explain why p150/dynactin is not recruited to the MT bundles. CLIP-170 targets the dynein/dynactin complex to the MT, using phopho-LIS1 as an adapter; the motor complex, being in the proximity of the MT, associates with it. The initial static link to the MT provided by CLIP-170 is released by its hyperphosphorylation and the retrograde dynein/dynactin-dependent movement of the cargo (endocytic vesicle, kinetochore, etc.) takes place. Doublecortin (DCX) is placed close to the LIS1 pathway based on its interaction with LIS1 and its role in microtubule dynamics. (This definition may be outdated - see the DesignNote.)
A humanized monoclonal antibody that recognizes carcinoembryonic antigen.
Late yaws is the tertiary, non-contagious stage of yaws, endemic tropical treponemal nonvenereal infection. Late yaws is characterized by destructive and deforming lesions of the skin, bones, and joints.
The complement cascade of proteolytic factors involved in cellular lysis can be initiated by several different factors, including antibody-dependent and antibody-independent recognition of infectious organisms. In the lectin-induced complement cascade, carbohydrates on the surface of microbial cells activate the complement cascade by binding to mannan-binding lectin (also called the mannan-binding protein, Mbl/Mbp). Mbp is an acute phase serum protein whose expression is induced by microbial infection. The binding of Mbl to microbial ligands activates the Mbl associated serine proteases Masp1 and Masp2, triggering the cleavage of C2 and C4 to create C4bC2a, a C3 convertase that cleaves large numbers of C3. Masp1 and Masp2 are similar to the C1 protease in the classical complement pathway. Once formed the C3 convertase cleaves and activates the remaining complement factors leading ultimately to formation of a pore in the bacterial membrane by the membrane attack complex (MAC) that lyses the bacterial cell. The lectin-induced pathway also appears to play an important role of the activation of phagocytotic cells by infection. Although the initiating event activating the complement cascade is distinct in the lectin-induced pathway, from the C3 convertase onward the lectin induced complement pathway is the same as the classical complement pathway. Since antibodies are not required in the lectin-induced pathway, this aspect of the immune response is part of the innate immune response. The importance of this pathway to the immune response has been demonstrated by the identification of children and adults with little or no Mbl who lacked normal phagocytotic responses and are highly susceptible to infection. (This definition may be outdated - see the DesignNote.)
An agent that inhibits metastasis by interfering with the interaction between tumor cells and lectins.
Leukotriene Degradation consists of conjugation, transport, and/or oxidation of a family of oxidative derivatives of arachidonic acid (5-lipoxygenase pathway) (leukotrienes) having potent regulatory effects on the activity of cardiovascular, pulmonary, central neural, gastrointestinal, and immune system cells involved in host defense, immediate hypersensitivity, and inflammation.
A process that involves the non-covalent binding of leukotrienes to one of three leukotriene receptors. These interactions are involved in neutrophil chemotaxis, endothelial cell adherence and cytokine production.
A non-neoplastic and self-limited condition that occurs during pregnancy. It is characterized by proliferation of luteinized stromal cells that replace the normal ovarian stromal cells. It is usually manifested with bilateral multinodular ovarian masses. Treatment is not required.
Lewis Y Antigen Binding involves non-covalent interaction of a molecule through intermolecular physical forces of attraction with the Lewis Y cell surface antigen.
An oral suspension of viscous lidocaine, diphenhydramine (Benadryl) and aluminum and magnesium hydroxides (Maalox). This agent possesses anesthetic, antihistamine, and antacid properties. (NCI04)
An adverse event that has life-threatening consequences; for which urgent intervention is indicated; that puts the patient at risk of death at the time of the event if immediate intervention is not undertaken.
Ligand Binding is the tight and specific (high affinity) interaction between a small molecule (typically) and a macromolecule (usually protein) that ordinarily results in modification of its function, e.g., antigen-antibody binding, hormone- or neurotransmitter-receptor binding.
Typically used in biomedical research, Linker-Oligonucleotides are usually short nucleic acids (DNA) that bridge or link, by complementary base pairing, two nucleic acids related by sequence and that lead to extension of the nucleic acid molecule. (NCI04)
An invasive breast carcinoma characterized by the presence of cytoplasmic neutral lipids in the vast majority of the malignant cells.
Nuclear receptors are transcription factors that are activated upon binding to its ligands. Initially, they had been classified as classic endocrine nuclear hormone receptors and orphan receptors. However, further studies have led to the identification of lipid ligands for some of these receptors, which are responsible for lipid metabolism, storage, and elimination. One of the characteristics of these receptors is that they act by forming heterodimers with retinoid X receptor (RXR). The receptors include peroxisome proliferators-Activated receptors (PPARs) for fatty acids, liver X receptor (LCR) for oxysterols, Farnesoid X receptors (FXR) for bile acids, and steroid xenobiotic receptor/X receptor (SXR/PXR or Nsil2) for xenobiotics. Other orphan receptors also requiring RXR for its functions are vitamin D receptor (VDR) for vitamin D and retinoic acid receptor (RAR) for retinoid acids, although these receptors are not involved in lipid metabolism. Upon binding to various ligands, three classes of proteins are synthesized including lipid binding proteins, the ATP-binding cassette (ABC) transporters and cytochrome P450 member proteins which catalyze lipid anabolism, metabolism, and elimination. In addition to lipid metabolism, some members of the cytochrome P450 family genes are responsible for activation of procarcinogens, detoxification of environmental toxins, and metabolism of drugs and xenobiotics. In particular, CAR, Nsil2, and recently identified VDR are important in up-regulation of these cytochromes. Of all the human cytochrome P450 genes, only a few CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 account for most toxicity effects, specifically CYP3A is responsible for clearing approximately half of the clinically prescribed drugs. For instance, acetaminophen, one of the most commonly used drug, is toxic in high doses due to the activation of CAR and the drug's subsequent conversion to acetyl-p-benzoquinone imine (NAPQI) by CYP1A2, CYP2E1 and CYP3A. (This definition may be outdated - see the DesignNote.)
Sterol-regulatory element binding proteins (SREBPs) play a key role in transcriptional regulation of cholesterol metabolism in response to cholesterol levels in the cell. When cholesterol is abundant in the cell, the SREBPs are retained in the ER. When cholesterol levels decrease, SREBPs are cleaved and released to act as transcription factors, binding to the promoters of genes such as the LDL receptor and HMG CoA Synthase. Binding of SREBPs to the LDL receptor promoter increases the expression of LDL receptor on the cell surface and increases the internalization of LDL from plasma, increasing cellular cholesterol levels and lowering LDL cholesterol in the plasma. Upregulation of genes such as HMG CoA synthase increases the biosynthesis of cholesterol. The SREBP proteins are cleaved and activated by two proteases, S1P (Site 1 protease) and S2P (Site 2 protease). S1P cleaves SREBP region in the ER lumen and S2P cleaves in the transmembrane region of SREBPs. Regulation by sterols is provided by SCAP. SCAP activates S1P when sterols are low, inducing SREBP activation, and does not activate S1P when sterol levels increase. Drugs acting at various steps in this process can alter cholesterol metabolism and plasma cholesterol levels that contribute to coronary heart disease. The statins such as lovastatin are drugs that inhibit cholesterol biosynthesis, lowering intracellular cholesterol levels and activating SREBP cleavage to increase LDLR expression on the cell surface. Inhibition of S1P may provide another mechanism to alter plasma cholesterol levels, as suggested by the low cholesterol levels in mice lacking the S1P gene. Ligands that bind to SCAP also lower cholesterol levels through induction of LDLR expression. (This definition may be outdated - see the DesignNote.)
Any substance that inhibits lipooxygenase, an enzyme that catalyses the dioxygenation of polyunsaturated fatty acids in lipids. Lipooxygenase is involved in the metabolism of eicosanoids (such as prostaglandins and leukotrienes) and its inhibition can suppress hypersensitivity reactions.
The situation where a person has survived a disease for years
A chromosomal abnormality that refers to the allelic loss of chromosome 1.
A cytogenetic abnormality that refers to the allelic loss of all or part of the long arm of chromosome 11.
A cytogenetic abnormality that refers to the allelic loss of all or part of the short arm of chromosome 12.
A chromosomal aberration where there is a loss of the long arm of chromosome 14. Loss of heterozygosity for chromosome 14q is associated with primary neuroblastomas.
A cytogenetic abnormality that refers to the allelic loss of all or part of the short arm of chromosome 17.
A cytogenetic abnormality that refers to the allelic loss of the chromosomal arm 19q. It has been described in gliomas and hemangiopericytomas.
A cytogenetic abnormality that refers to the allelic loss of the chromosomal arm 1p. It has been described in gliomas, meningiomas, neuroblastomas, hepatocellular carcinomas, breast carcinomas, acinar prostate adenocarcinomas, pancreatic carcinomas, and adrenal gland adenomas.
A chromosomal abnormality that refers to the allelic loss of chromosome 3.
A cytogenetic abnormality that refers to the loss of all or part of the short arm of chromosome 3.
A cytogenetic abnormality that refers to the allelic loss of all or part of the long arm of chromosome 6.
A cytogenetic abnormality that refers to deletion of part of the long arm of chromosome 7. It is associated with the development of chronic myelomonocytic leukemia with eosinophilia, refractory anemia with excess blasts, refractory anemia with multilineage dysplasia, and refractory anemia with multilineage dysplasia and ringed sideroblasts.
A structural cytogenetic abnormality characterized by partial or complete loss of chromosome 8.
A cytogenetic abnormality that refers to deletion of part of the long arm of chromosome 9. It is associated with the development of acute myeloid leukemia and various types of carcinomas.
A cytogenetic abnormality that refers to deletion of the sex-determining chromosome Y. It is associated with the development of the accelerated and blast phases of chronic myelogenous leukemia, BCR-ABL1 positive, and various types of carcinomas.
A molecular abnormality indicating the absence of merlin protein.
A precancerous neoplastic process that affects the cervical squamous epithelium without evidence of invasion. It is usually associated with human papillomavirus infection. It is characterized by the presence of mild atypia in the superficial epithelial layer that may be associated with koilocytosis. Maturation is present in the upper two thirds of the epithelium. Mitotic figures are not numerous and are present in the basal third of the epithelium.
A papillary transitional cell carcinoma of the urinary bladder, characterized by minimal cytologic atypia and infrequent mitotic figures (usually limited to the lower half of the tumor). This type of carcinoma recurs frequently, may invade the bladder wall, and has a low risk of progression.
A low grade metaplastic carcinoma of the breast with morphologic features similar to the adenosquamous carcinoma of the skin. In the majority of cases the prognosis is excellent.
A rare invasive mesenchymal tumor that arises from the ovary. It is characterized by the absence of marked pleomorphism and nuclear atypia in the neoplastic mesenchymal cells. It may have a favorable clinical outcome.
An intermediate fibroblastic neoplasm arising from the lung. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes and plasma cells.
A synthetic analogue of the endogenous hormone gonadotropin-releasing hormone (GnRH), with potential antineoplastic activity. Upon administration, GnRH analogue mimics endogenous GnRH and strongly binds to and activates pituitary GnRH receptors, which stimulates the synthesis and secretion of the gonadotropic hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Continuous, prolonged activation by the GnRH analogue results in pituitary GnRH receptor desensitization and receptor downregulation. This causes inhibition of pituitary gonadotropin secretion of LH and FSH. In males, the inhibition of LH secretion prevents the production and release of testosterone from Leydig cells in the testes and causes a significant decline in testosterone production that is near the levels seen after castration. This may inhibit androgen receptor-positive tumor progression. In females, this results in a decrease in estradiol production. GnRH, also called luteinizing hormone-releasing hormone (LH-RH), is normally synthesized in and secreted by the hypothalamus. Synthetic analogues of GnRH have a stronger receptor binding affinity than the endogenous form.
A radioimmunoconjugate consisting of a humanized monoclonal antibody directed against the extracellular domain of prostate-specific membrane antigen linked to a beta-emitting radioisotope (lutetium-177). This radioimmunoconjugate binds to tumor cells that express the extracellular domain of prostate-specific membrane antigen, delivering beta particle radiation selectively to tumor cells expressing this antigen and so limiting the exposure of normal tissues to ionizing radiation.
An antiquated term that refers either to nodular lymphocyte predominant Hodgkin lymphoma or to lymphocyte-rich classical Hodgkin lymphoma.
A phase of the virus life cycle during which the virus replicates within the host cell, releasing a new generation of viruses when the infected cell lyses.
A cancer vaccine consisting of a recombinant vaccinia virus encoding the tumor-associated gene MAGE-1 that is contaminated with bovine viral diarrhea virus (BVDV). The MAGE-1 gene is a member of the melanoma antigen-encoding gene family which is expressed in various malignant tumors such as hepatocellular carcinoma and germ cell tumors in addition to melanoma. Vaccination with vaccinia virus expressing human MAGE-1 may generate antitumoral T-cell responses. BVDV is an RNA pestivirus that may contaminate vaccines due to its presence in the fetal calf serum used as a growth supplement in the tissue culture of mammalian cells used in vaccine production. (NCI04)
The binding of b-arrestins to agonist-occupied GPCRs triggers the assembly of a MAP kinase activation complex using b-arrestin as a scaffold, with subsequent activation of a b-arrestin-bound pool of ERK1/2. The receptor-b-arrestin-ERK complexes are localized to endosomal vesicles, and their formation does not result in nuclear translocation of activated ERK1/2 or stimulation of cell proliferation. The function of b-arrestin-bound ERK1/2 is presently unknown. Activation of ERK1/2 by b-arrestin scaffolds may favor the phosphorylation of plasma membrane, cytosolic, or cytoskeletal ERK1/2 substrates, or it may lead to transcriptional activation through the ERK-dependent activation of other kinases. The model depicts b-arrestin scaffolding of the ERK1/2 MAP kinase cascade, based upon data obtained with the protease-activated PAR2 and angiotensin AT1a receptors. A similar mechanism has been proposed for regulation of the JNK3 MAP kinase cascade by AT1a receptors. (This definition may be outdated - see the DesignNote.)
Map kinases transduce responses to extracellular signals by a variety of routes, and communicate with other pathways through extensive crosstalk networks. A closely studied Map kinase cascade originates with tyrosine kinase activation, and activation of Ras. Ras activates Raf, Raf activates the Map kinase kinases Mek1 and Mek2 and these kinases activate downstream Map kinases like Erk1 and Erk2. Erk1 and Erk2 in turn activate transgenes like p35 through the Map kinase activated transcription factor EGR-1. Mek1 plays a central role in many different Map kinase pathways. Factors that activate Mek1 include growth factors like NGF, cytokines, chemokines, and phorbol ester, resulting in cellular proliferation and survival. Mek1 activation may also play a role in differentiation in neuronal tissues. In cultured neuronal PC-12 cells, NGF induces neurite outgrowth via Mek1 and the map kinase pathway. Constitutive activation of Mek1 can transform cells and may play a role in cancer. The crucial role of Mek1 in a variety of pathways including cellular transformation suggests that the cell must tightly regulate its activity. Cdk5 is a kinase that regulates the activity of Mek1. Although Cdk5 is a member of the cyclin-dependent kinase gene family, the activity of Cdk5 does not appear to be regulated by cyclins, but is activated by association with p35. Cdk5 does not act as a checkpoint kinase to regulate cell cycle progression, but acts as a regulatory kinase involved in other post-mitotic processes such as neuronal activity such as neuronal migration during development and neurite outgrowth. Mice lacking Cdk5 exhibit defects in neuronal development. One target of Cdk5 is Mek1. Phosphorylation of Mek1 by Cdk5 represses Mek1 activity and blocks downstream cellular responses. The activation of p35 by Map kinase pathways followed by deactivation of Map kinase signaling by the Cdk5/p35 complex completes the loop of a feedback circuit to terminate Map kinase signaling. (This definition may be outdated - see the DesignNote.)
Mitogen-activated protein (MAP) kinases are important players in signal transduction pathways activated by a range of stimuli and mediate a number of physiological and pathological changes in cell function. There are three major subgroups in the MAPK family: ERK, p38, and JNK/SAPK. ERK is activated mainly by mitogenic stimuli, whereas p38 and JNK/SAPK are activated mainly by stress stimuli or inflammatory cytokines. MAP kinases are part of a three-tiered phosphorylation cascade and MAP kinase phosphorylation on a threonine and tyrosine residue located within the activation loop of kinase subdomain VIII results in activation. However, this process is reversible even in the continued presence of activating stimuli, indicating that protein phosphatases provide an important mechanism for MAP kinase control. Dual specificity phosphatases (DSPs) from the tyrosine phosphatase (PTP) gene superfamily are selective for dephosphorylating the critical phosphothreonine and phosphotyrosine residues within MAP kinases. Ten members of dual specificity phosphatases specifically acting on MAPKs, termed MAPK phosphatases (MKPs), have been reported. They share sequence homology and are highly specific for MAPKs but differ in the substrate specificity, tissue distribution, subcellular localization, and inducibility by extracellular stimuli. MKPs have been shown to play important roles in regulating the function of the MAPK family. DSP gene expression is induced strongly by various growth factors and/or cellular stresses. Expression of some gene family members, including CL100/MKP-1, hVH-2/MKP-2, and PAC1, is dependent at least in part on MAP kinase activation providing negative feedback for the inducing MAP kinase or for regulatory cross talk between parallel MAP kinase pathways. DSPs are localized to different subcellular compartments and certain family members appear highly selective for inactivating distinct MAP kinase isoforms. This enzymatic specificity is due to catalytic activation of the DSP phosphatase after tight binding of its amino-terminal to the target MAP kinase. Thus, DSP phosphatases provide a sophisticated mechanism for targeted inactivation of selected MAP kinase activities. (This definition may be outdated - see the DesignNote.)
A peptide-based cancer vaccine consisting of amino acid residues 26 through 35 of MART-1 (melanoma antigen recognized by T-cells-1) with a leucine substitution at amino acid position 27 to improve immunogenicity. Upon administration, MART-1:26-35(27L) peptide vaccine may induce a cytotoxic T-lymphocyte (CTL) response against MART-1-expressing tumor cells, resulting in decreased tumor growth. The tumor-associated antigen (TAA) MART-1 may be overexpressed on melanoma cancer cells.
A vaccine consisting of recombinant adenovirus vector encoding MART-1 (melanoma antigen recognized by T-cells 1), an immunogenic protein of unknown function that is expressed by certain types of melanoma. Vaccination with MART-1 adenovirus vaccine may stimulate the host immune system to direct cytotoxic T lymphocytes (CTL) against MART-1 positive melanoma cells, resulting in an antitumor effect. (NCI04)
A synthetic cancer vaccine derived from a melanoma-associated antigen, MART-1. Antigenic peptides derived from MART-1 are recognized by CD8+ T lymphocytes and have been used to immunize patients with advanced melanomas; prolonged immunization may result in a reduction in tumor size. Fowlpox virus is an attractive vector because its genome is easy to manipulate and it does not multiply in human tissues. (NCI04)
A cancer vaccine consisting of an attenuated recombinant vaccinia virus expressing the melanoma-associated antigen MART-1. Vaccination with this agent may stimulate cytotoxic host immune responses to melanoma cells. (NCI04)
A monoclonal antibody used to purge leukemia cells from bone marrow. (NCI)
A bispecific antibody containing a patented Trigger antibody and a humanized antibody that targets TAG-72. TAG-72 is overexpressed in a variety of cancers.
A change in the nucleotide sequence of the MET gene.
A vaccine that contains the GM2 and GD2 antigens separately coupled to the carrier protein Keyhole Limpet Hemocyanin and mixed with QS-21 adjuvant (an immune system stimulant), designed to stimulate a patient's immune system to control or eradicate residual cancer cells after surgery, radiation or chemotherapy. (NCI)
MHC Interaction involves temporary non-covalent binding of a molecule through intermolecular physical forces of attraction with protein complexes on the surface of diverse cell types that typically mediate cellular cooperation in the immune response.
Expression of a fusion protein that results from the insertion mutation ins(5;11)(q31;q13q23), which involves the human genes KMT2A and AFF1 and is associated with acute lymphoblastic leukemia.
Expression of a fusion protein that results from a t(9;11)(p22;q23) translocation, which involves the human genes KMT2A and MLLT3 and is associated with many leukemias.
Expression of a fusion protein that results from a t(11;19)(q23;p13.3) translocation which fuses the 5' half of the KMT2A gene to most of the MLLT1 gene and is associated with acute lymphoblastic leukemia and other leukemia types.
A monoclonal antibody B3, recognizing the tumor-associated Lewis Y antigen, is conjugated to a backbone-substituted derivative of DTPA, 2-(p-isothiocyanatobenzyl)-cyclohexyl-diethylenetriaminepentaacetic acid (CHX-A DTPA). DTPA is a bifunctional chelating agent thereby allowing for the binding of radioisotopes to the immunoconjugate.
A recombinant, murine monoclonal antibody directed against gastrin-releasing peptide, one of a number of bombesin-like peptides (BLP). Tumor cells, such as small cell lung cancer (SCLC) cells, express and secrete BLP that activate specific cell growth-promoting receptors. Monoclonal antibody 2A11 has been shown to decrease the growth of SCLC cells in vitro and in animal models. (NCI04)
Peripheral blood lymphocytes (PBL) transfected to express MOv have been designed for possible use in autologous adoptive cellular immunotherapy of ovarian adenocarcinomas that overexpress folate-binding protein. MOv-PBLs express MOv-gamma (MOv), a chimeric receptor gene product derived from a recombinant gene encoding the variable region of murine monoclonal antibody MOv18 against folate-binding protein (FBP), often overexpressed in human ovarian cancer cells, and the human gene encoding the IgG and IgE Fc receptor gamma subunit. Autologous vaccination with these PBLs stimulates a host cytotoxic T lymphocyte response against ovarian cancer cells that overexpress FBP. (NCI04)
MSP, macrophage-stimulating protein, acts through the transmembrane receptor kinase RON (Stk in mice) to play a role in inflammation and the response to tissue injury. MSP is secreted by the liver into the blood as pro-MSP, an inactive precursor form. MSP is related to clotting factors that are activated by proteolytic cleavage and pro-MSP is itself also activated by cleavage to MSP. Binding of activated MSP heterodimer to RON expressed on macrophages, monocytes and keratinocytes stimulates activation of the RON kinase and second messenger pathways, including PI-3 kinase. Macrophages respond to MSP with changes in cell shape and motility and keratinocytes respond by proliferating. Tissue injury leads to pro-MSP cleavage and activation, and macrophages and keratinocytes that respond to MSP are key cells in tissue injury response, supporting a role for MSP and RON in the response to tissue injury. The interaction of MSP and macrophages at sites of inflammation such as infection also depends on chemotactic factors such as MCP1 and inflammatory cytokines such as IL-1 and TNF that attract and activate immune cells in the affected tissue. (This definition may be outdated - see the DesignNote.)
Most of the energy derived from the oxidation of glucose is not extracted directly as ATP, but as reduced NADH that transfers high-energy electrons to the electron transport chain in the inner mitochondrial membrane. This NADH comes primarily from the Krebs cycle in the mitochondrial matrix and is therefore directly accessible to electron transport. NADH generated during glycolysis cannot reach the electron transport chain directly however and there is no direct mechanism for the transfer of NADH across the mitochondrial membrane. Instead shuttle mechanisms have evolved to move the energy of reduced NADH across the membrane in the form of other reduced molecules. One shuttle is the glycerophosphate shuttle and another is the malate-aspartate shuttle. The malate-aspartate shuttle occurs in mammalian tissues. First, oxaloacetate on the cytoplasmic side is reduced by NADH, creating malate and NAD+. Malate and the electrons it carries are transported into the mitochondria across the inner mitochondrial membrane, in exchange for alpha-ketoglutarate, which is transported out of the mitochondria. Once inside, the energy in malate is extracted again by reducing NAD+ to make NADH, regenerating oxaloacetate. This NADH is then free to transfer its high energy electrons to the electron transport chain. The oxaloacetate is transaminated with glutamate to make aspartate and alpha-ketoglutarate. Aspartate is returned to the cytosol by the aspartate-glutamate transporter, which moves glutamate into the mitochondria as it transports aspartate out. The overall result is that NADH is transported into the mitochondria, and can be used to generate 3 ATP per every NADH transported in from the cytosol, a very efficient process. (This definition may be outdated - see the DesignNote.)
Substances that demonstrate efficacy in treating tumor induced hypercalcemia.
An invasive malignant tumor that arises from the breast. It is characterized by the presence of spindle-shaped myoepithelial cells. Mitoses are present. Rarely, local recurrences and distant metastases have been reported.
A mixed epithelial and mesenchymal neoplasm that arises from the cervix and is characterized by the presence of malignant mesenchymal elements and benign or malignant epithelial elements. This category includes adenosarcoma and carcinosarcoma.
The transformation of a cell or cell population from a pre- or non-malignant condition to a malignant condition. (NCI)
An antiquated term that refers to a morphologic variant of non-Hodgkin lymphoma which is composed predominantly or exclusively of large neoplastic lymphocytes.
An invasive malignant neoplasm that arises from the ovary and is characterized by a predominance of clear and hobnail malignant epithelial cells.
An invasive malignant neoplasm that arises from the ovary characterized by the presence of malignant, endometrial-type cells. It includes endometrioid adenocarcinoma and carcinosarcoma.
A malignant mixed epithelial neoplasm that arises from the ovary and is composed predominantly of serous and endocervical-type mucinous epithelium.
An invasive malignant neoplasm that arises from the ovary and is characterized by the presence of malignant epithelial cells that contain intracytoplasmic mucin and may resemble the epithelial cells of the endocervix or gastrointestinal tract. It includes mucinous adenocarcinoma and mucinous adenocarcinofibroma.
An invasive malignant neoplasm that arises from the ovary and is characterized by the presence of malignant epithelial cells that, in well differentiated tumors, resemble the epithelium of the fallopian tube or, in poorly differentiated tumors, show anaplastic features and marked nuclear atypia. It includes serous adenocarcinoma and serous adenocarcinofibroma.
An invasive malignant tumor that originates from the surface epithelium of the ovary. It is composed of malignant epithelial cells and stroma. Representative examples include serous adenocarcinoma, mucinous adenocarcinoma, endometrioid adenocarcinoma, clear cell adenocarcinoma, and malignant Brenner tumor.
An invasive malignant neoplasm that arises from the ovary and is characterized by the presence of malignant epithelial cells that resemble malignant urothelial cells. It includes transitional cell carcinoma and malignant Brenner tumor.
The N-substituted benzamide metoclopramide, a potential radiosensitizer, which inhibits DNA repair and induces apoptosis. (NCI)
The origin or causation of a disease of the nervous system.
Processes by which certain microorganisms and toxins are attracted to nervous tissue.
A nevus that arises from the female genital organs. This category includes congenital nevus, acquired nevus, dysplastic nevus, blue nevus, and atypical melanocytic nevus of the genital type.
An invasive, non-metastasizing neoplasm with sweat duct differentiation that arises in the area of the nipple. Local recurrences have been reported.
Nitric oxide (NO) has a number of important physiological actions in the cardiovascular system. In the heart, NO plays a role in keeping the vessels open via vasodilation and prevention of platelet aggregation. It also plays an important role in regulating the force and rate of contraction. In vivo NO is released by shear stress of ligands that increase intracellular Ca2+ in endothelial cells. The increased intracellular Ca2+ activates nitric oxide synthase III (NOSIII) by promoting the binding of Ca/Calmodulin to the enzyme. NOSIII, which is resident in the Golgi complex, is transported together with caveolin-1 to the caveolae at the plasma membrane via vesicles. Shear stress signals via a potassium channel and the cytoskeleton, which results in tyrosine phosphorylation of specific proteins, activation of phosphatidylinositol 3-kinase, and subsequently in activation of Akt kinase. Akt activation by shear stress, but also by VEGF, activates NOSIII by serine phosphorylation, which increases the affinity of NOSIII for calmodulin. After agonist binding at the plasma membrane, NOSIII-activating receptors translocate to caveolae. VEGF receptor signals via its tyrosine kinase domain. Furthermore, agonist receptors activate calcium channels of the endoplasmic reticulum (ER) via phospholipase C and inositol 1,4,5-trisphosphate. This calcium flux induces binding of calmodulin to NOSIII, whereas the NOSIII-caveolin-1 interaction is disrupted. At the same time, NOSIII is translocated into the cytosol. On binding of calmodulin, NOSIII generates NO, is enhanced by the interaction with Hsp90. Once activated, NOSIII catabolizes L-arginine to NO, which diffuses out of the cell. NO stimulates guanylate (G-) cyclase and increases cGMP levels. cGMP activates cGMP-dependent protein kinase (PKG), cGMP-inhibited phosphodiesterase (PDEIII), and cGMP-stimulated phosphodiesterase (PDEII). PKG may reduce the force and rate of contraction, possibly by phosphorylating troponin I or by phosphorylating phospholamban. PDEIII is inhibited by the increases in cGMP brought about by NO. This may result in an increase in cAMP and cAMP-dependent protein kinase (PKA). PKA in turn activates Ca2+ channels, countering the effects of PKG. In contrast, cGMP may stimulate PDEII, reduce cAMP levels and PKA activity, and thereby reduce Ca2+ channel activity. (This definition may be outdated - see the DesignNote.)
Glutamatergic-mediated nitric oxide (NO) production occurs via the N-methyl-D-aspartic acid (NMDA) postsynaptic density protein 95 (PSD95)-neuronal nitric oxide synthase (NOS1) ternary complex. The increased intracellular Ca2+ stimulates the interaction of nNOS and calmodulin (CaM) and the translocation of nNOS from the plasma membrane to the cytoplasm. The dephosphorylation of nNOS by Calcineurin catalyzes the conversion of arginine to citrulline and nitric oxide (NO), which turns on guanylate cyclase and the various cGMP regulated signaling pathways. (This definition may be outdated - see the DesignNote.)
Nitrosamine Metabolism involves important cellular biochemical detoxification reactions that chemically modify the N-nitroso derivatives of secondary amines, formed by the combination of nitrates with amines. Some nitrosamines show carcinogenic activity; under certain conditions, nitrite-containing foods can form nitrosamines.
Diagnostic tests fail to detect presence of disease.
An impulse that gives rise to sensations of pain.
A term that usually refers to the clinical course of lymphomas and indicates that the cancerous lymph nodes are not next to each other, but are on the same side of the diaphragm.
A malignant germ cell tumor that arises from the ovary and is composed of cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts. The prognosis is less favorable than gestational choriocarcinoma.
A variant of cervical squamous cell carcinoma characterized by the presence of polygonal squamous cells. Intercellular bridges and cytoplasmic keratinization may be present, but keratin pearls are absent.
A disorder of the blood. Some nonmalignant hematologic disorders may lead to leukemia.
A category of non-neoplastic trophoblastic disorders that affect the placenta. It includes the exaggerated placental site and placental site nodule or plaque.
An aromatase inhibitor with a non-steroidal structure. Non-steroidal aromatase inhibitors work by reversible competition with the enzyme.
Non-Voltage-Dependent Calcium Channels are membrane-associated protein-based structures that regulate the movement of calcium ions through cellular membranes, independent of the transmembrane potential gradient, to affect cellular homeostatic conditions and/or signaling processes.
Any adverse experience that does not meet the definition of serious. Non-serious adverse events are classified as mild, moderate and severe.
Presenilin-1 (PS1) is associated with gamma secretase activity that cleaves amyloid precursor protein (APP) and is implicated in Alzheimer's disease. Presenilin-1 is also a component in gamma-secretase activity involved in signaling by the transmembrane protein Notch. Active gamma secretase requires PS-1 N-terminal fragment and a C-terminal fragment and is unique in catalyzing proteolysis within the transmembrane region of proteins. Other proteins such as nicastrin may also be components of the gamma-secretase. Binding of the ligand Delta by Notch appears to trigger two proteolytic cleavages of Notch. The first step cleaves an extracellular domain and is catalyzed by a metalloprotease termed alpha-secretase or TACE. The second cleavage step appears to occur within the transmembrane domain of Notch, and releases a Notch intracellular domain (NICD). Once released, NICD moves into the nucleus where it is involved in transcriptional regulation through CSL family transcription factors (CBF1, Su(H), Lag-1) or other transcriptional regulators such as LEF-1. Presenilin is also involved in the Wnt/frizzled signaling pathway through beta-catenin. Beta-catenin is a cytoskeletal component that enters the nucleus to act as a transcriptional cofactor. Binding of WNT to Frizzled causes disheveled (DSH) to inhibit Glycogen synthase kinase 3 beta (GSK-3b) activity. Phosphorylation of Beta-catenin induces the ubiquitination and proteolytic degradation of beta-catenin by the proteasome. Non-phosphorylated beta-catenin is stable and enters the nucleus to regulate transcription with TCF. The beta-catenin/TCF complex activates genes that promote cellular survival, proliferation and differentiation during development. Presenilin stimulates beta-catenin turnover, reducing its transcriptional activation. (This definition may be outdated - see the DesignNote.)
A nitrogen mustard agent that crosslinks with DNA, causing inhibition of DNA synthesis. (NCI)
Having nuclei with various distinct forms.
Nuclear Translocation is a subcellular process in which activated cytoplasmic proteins are transported into the cell nucleus as part of a signal transduction pathway to modify cell function (typically gene expression) in response to a signaling event or condition.
Process by which a nucleic acid macromolecule assumes an energetically favorable three-dimensional conformation as a result of intrinsic and extrinsic atomic physical forces. (NCI)
A process that involves the non-covalent binding of nucleosides to nucleoside receptor proteins. This interaction plays a role in the initiation of signal transduction.
Nucleotide Metabolism Alteration involves a change in the quality of the existing state of activities of biologic molecules or complexes involved in the enzymatic formation or degradation of nucleoside phosphates, the monomeric building blocks from which DNA or RNA polymers are constructed.
An irregularity in the number of chromosomes.
O-glycans are a class of glycans that modify serine or threonine residues of proteins. Biosynthesis of O-glycans starts from the transfer of N-acetylgalactosamine (GalNAc) to serine or threonine. The first GalNAc may be extended with sugars including galactose, N-acetylglucosamine, fucose, or sialic acid, but not mannose, glucose, or xylose. Depending on the sugars added, there are four common O-glycan core structures, cores 1 through 4, and an additional four, cores 5 though 8. Mucins are highly O-glycosylated glycoproteins ubiquitous in mucous secretions on cell surfaces and in body fluids. Mucin O-glycans can be branched, and many sugars or groups of sugars are antigenic. Important modifications of mucin O-glycans include O-acetylation of sialic acid and O-sulfation of galactose and N-acetylglucosamine.
Nuclear hormone receptors are transcription factors that bind DNA and regulate transcription in a ligand-dependent manner. PPAR-gamma is a member of this gene family that is activated by fatty acids and thiazolidinedione drugs that plays a role in insulin sensitivity and adipogenesis. Like PPAR-alpha and other members of this gene family, PPAR-gamma activates transcription in concert with coactivators including Src-1 and Tif2. Although these coactivators act for multiple members of this gene family, coactivators may have specific functions in some settings. Deletion of the Src-1 gene or Tif2 gene in mice reduced the response to steroid hormones and development dependent on these hormones. Some PPAR-gamma ligands induce the specific recruitment of coactivators, and might evoke different functional responses based on the interactions they favor. The natural ligand 15-deoxy prostaglandin J2 stimulated PPAR-gamma interaction with SRC-1, TIF2, TRAP220, and p300, while the synthetic PPAR-gamma ligand troglitazone, an antidiabetic thiazolidinedione drug, did not promote these interactions, indicating that other distinct coactivators may mediate the response to PPAR-gamma when it binds this ligand. In normal rodents, a high-fat diet leads to high levels and free fatty acids and PPAR-gamma activation in white adipose tissue, stimulating fat uptake, adipogenesis and obesity. PPAR-gamma activation in brown adipose tissue depends mainly on Src-1 as a coactivator and Src-1 is essential for PGC-1 alpha to act as a coactivator to stimulate thermogenesis. Regulation of energy use by PGC-1 in other tissues such as muscle may contribute to weight loss associated with cancer and increased metabolism induced by exercise. High-fat feeding and high plasma free fatty acids reduce thermogenesis in brown fat due to the greater requirement of PPAR-gamma for Src-1 than Tif2 for activation in these cells. In white adipose cells, Tif2 predominates as the PPAR-gamma coactivator, stimulating fat uptake and adipogenesis in conditions of high-fat feeding. Trap220, a component of the TRAP coactivator complex, is also required for adipogenesis. Examining the metabolic consequences of coactivator deletion, Src-1 and Tif2 specifically alter PPAR-gamma signaling. Compared to normal rodents, Mice lacking the Tif2 coactivator are resistant to obesity when fed a high-fat diet, with increased lipolysis in adipocytes and decreased fatty acid uptake in adipose tissue. A high-fat diet increases the expression of Tif2 in both brown and white adipose cells, changing the Tif2 to Src-1 ratio. This change in the ratio of coactivators favors increased adipogenesis in white adipose while it blocks thermogenesis in brown adipose cells by opposing Src-1/PGC-1 alpha dependent signaling. (This definition may be outdated - see the DesignNote.)
Passage or transfer, as of a disease, to a recipient individual within or due to occupational circumstances. (NCI)
A gastrointestinal stromal tumor that arises from the omentum. This is an extragastrointestinal tumor, meaning that it does not arise directly from the gastrointestinal tract.
A rare breast adenocarcinoma characterized by the presence of neoplastic oncocytic cells. The oncocytic cells comprise more than 70 percent of the malignant cellular population.
Any DNA sequence alteration process occurring in a proto-oncogene, resulting in loss of regulation of the gene product, and predisposing the cell to neoplastic transformation. Proto-oncogenes are ordinarilly involved in transduction of signals that regulate cell growth and differentiation. Activation of such genes overrides the normal mechanisms of regulation and is an important step in the process of cellular transformation.
A cancer vaccine consisting of a mixture of a murine lymphoma-derived idiotype and interleukin-2 (IL-2) encapsulated in dimyristoylphosphatidylcholine liposomes. The use of a liposomal carrier confers immunogenicity to the naturally non-immunogenic idiotype. (NCI04)
A process that involves the non-covalent binding of opioids to one of four opioid receptors. These interactions are involved in mediation of analgesia, euphoria, and physical dependence to opioids.
Any substance that inhibits ornithine decarboxylase, an enzyme that catalyzes the decarboxylation of ornithine, the rate-limiting, commiting reaction in polyamine synthesis. Polyamines are important for stabilizing DNA structure, for the DNA double strand-break repair pathway, and as antioxidants, and inhibition of ornithine decarboxylase inhibits cell growth.
Any substance that inhibits orotidine 5'-phosphate decarboxylase (orotidylate decarboxylase), an enzyme that catalyzes the decarboxylation of orotidine monophosphate to form uridine monophosphate and is required for the de novo synthesis of uridine and pyrimidines. Inhibition of orotidine 5'-phosphate decarboxylase inhibits DNA, RNA, and protein synthesis.
The result of therapy for a given disease or condition in a patient or group of patients.
A germ cell tumor that arises from the ovary and is composed of tissues that originate from two or three of the following germ layers, endoderm, ectoderm, or mesoderm.
A malignant glandular epithelial neoplasm characterized by the presence of clear and hobnail cells. It is highly associated with ovarian endometriosis, pelvic endometriosis and paraendocrine hypercalcemia.
An uncommon benign neoplasm of glandular epithelium characterized by the presence of clear or hobnail cells within a dense fibrous stroma.
A benign neoplasm of glandular epithelium characterized by the presence of clear or hobnail cells within a dense fibrous stroma and cystic structures.
A secondary adenocarcinoma that has developed in an ovarian dermoid cyst.
A secondary angiosarcoma that has developed in an ovarian dermoid cyst.
A corticotropin secreting adenoma that has developed in an ovarian dermoid cyst. It may present with Cushing syndrome. The clinical course is benign.
A secondary leiomyosarcoma that has developed in an ovarian dermoid cyst.
A secondary melanocytic nevus that has developed in an ovarian dermoid cyst.
A secondary melanoma that has developed in an ovarian dermoid cyst.
A prolactin secreting adenoma that has developed in an ovarian dermoid cyst. It may present with hyperprolactinemia and amenorrhea. The clinical course is benign.
A secondary sebaceous adenoma that has developed in an ovarian dermoid cyst.
A secondary sebaceous carcinoma that has developed in an ovarian dermoid cyst.
A secondary carcinoma that has developed in an ovarian dermoid cyst. In the majority of cases, the secondary carcinoma is a squamous cell carcinoma.
A secondary melanoma or melanocytic nevus that has developed in an ovarian dermoid cyst.
A secondary corticotropin secreting adenoma or prolactin secreting adenoma that has developed in an ovarian dermoid cyst. The clinical course is benign.
A secondary sarcoma that has developed in an ovarian dermoid cyst. Representative examples of secondary sarcomas include leiomyosarcoma, fibrosarcoma, and angiosarcoma.
A secondary sebaceous adenoma or sebaceous carcinoma that has developed in an ovarian dermoid cyst.
A secondary squamous cell carcinoma that has developed in an ovarian dermoid cyst.
A malignant neoplasm of the ovary characterized by the presence of malignant glandular cells resembling endometrial cells in a fibrotic stroma.
A benign neoplasm of the ovary characterized by the presence of cystic structures lined by endometrial-type well-differentiated cells.
A rare type of teratoma that arises from the ovary and resembles a malformed fetus.
A neoplasm that arises from the ovary and is composed of tissues that resemble dysgerminoma or seminoma and are admixed with sex cord tissues. It is found in children or young adults and usually is associated with secondary sex organs abnormalities. The majority of patients present as phenotypic females with virilization. The minority of patients present as phenotypic males with feminization. It typically affects both gonads. If a malignant germ cell component is present, it may metastasize to other anatomic sites.
A carcinoid tumor that arises from the ovary and is characterized by the presence of round cells with abundant eosinophilic cytoplasm forming cribriform patterns. Clinical manifestations of carcinoid syndrome occur in approximately thirty percent of patients. The prognosis is favorable.
A Leydig cell tumor that arises from the ovarian stroma.
A lymphoma that affects the ovary. Lymphomatous involvement of the ovary is rare and in approximately half of the cases both ovaries are affected.
A rare malignant mesothelial neoplasm that usually involves both the ovarian surface and the ovarian stroma. In most cases there is bilateral ovarian involvement.
A benign neoplasm of the ovary characterized by the presence of glands with mucinous columnar epithelial cells in a fibrotic stroma.
A rare carcinoid tumor that arises from the ovary and is characterized by the presence of glands that are lined by cells that contain intracytoplasmic mucin or resemble goblet cells. Pools of mucin, containing glands, may also be present. It may have an aggressive clinical course and it can metastasize to other anatomic sites.
A benign neoplasm of the ovary characterized by the presence of cystic structures lined by mucinous columnar epithelial cells in a fibrotic stroma.
The presence of abundant mucoid or gelatinous, cellular or acellular material in the pelvis and abdominal cavity (pseudomyxoma peritonei) that is associated with the presence of an ovarian mucinous cystic tumor. In the vast majority of cases, the presence of pseudomyxoma peritonei is the result of metastasis from a primary appendiceal or gastrointestinal tumor site, and the ovarian mucinous tumor is metastatic rather than primary.
A malignant tumor that arises from the ovary and is characterized by the presence of malignant germ cell components but lacks a teratoma component.
A Sertoli-Leydig cell tumor of the ovary in which anastomosing, slit-like spaces resembling rete testis constitute at least 90% of the tumor elements. It may present with estrogenic and less often androgenic manifestations. It usually follows a benign clinical course.
A benign neoplasm of the ovary characterized by the presence of glands with serous epithelial cells in a fibrotic stroma.
A Sertoli-Leydig cell tumor that arises from the ovary. It is characterized by the presence of epithelial and/or mesenchymal components and neoplasms that arise from these components.
A Sertoli-Leydig cell tumor characterized by the presence of spaces that resemble rete testis (retiform elements). These spaces form anastomosing patterns and comprise at least ten percent but less than ninety percent of the tumor. When the retiform elements comprise ninety percent or more of the tumor, the term retiform Sertoli-Leydig cell tumor is used. A minority of patients may have an aggressive clinical course.
A sex cord-stromal tumor that arises from the ovary and is composed entirely of, or in various combinations of, Sertoli cells, Leydig cells, and fibroblast-like cells.
A sex cord-stromal tumor that arises from the ovary in a patient diagnosed with Peutz-Jeghers syndrome.
A sex cord-stromal tumor that arises from the ovary and lacks the morphologic features that belong to the categories of granulosa-stromal tumors, Sertoli-stromal tumors, or steroid cell tumors.
A rare, benign sex cord-stromal tumor that arises from the ovary and is characterized by the presence of round cells with a single cytoplasmic vacuole and an eccentric nucleus resembling signet ring cells. Mucin stains are negative.
An undifferentiated small cell carcinoma that arises from the ovary and is associated with hypercalcemia. Electron microscopic studies show neurosecretory granules are either absent or, when present, are in small numbers.
An aggressive small cell neuroendocrine carcinoma that arises from the ovary. Morphologically, it resembles the small cell carcinoma that arises from the lung.
A squamous cell tumor that arises from the ovary and is not associated with a germ cell tumor.
A steroid cell tumor that arises from the ovary and is defined by morphologic features that do not fit into the categories of Leydig cell tumor and stromal luteoma. These features include solid proliferations of polygonal neoplastic cells with eosinophilic and granular cytoplasm. Grossly, these tumors usually present as large and well circumscribed masses and are usually associated with androgenic manifestations. Approximately one third of the cases have a malignant clinical course.
A rare, benign and well circumscribed stromal tumor of the ovary. It is characterized by the presence of a fibrotic stroma with clusters of Leydig cells. The Leydig cells contain crystals of Reinke. Patients may present with virilization.
A non-neoplastic disorder that usually affects postmenopausal women. It is characterized by proliferation of ovarian stromal cells without evidence of atypia. There is usually bilateral ovarian involvement. The ovaries may or may not be enlarged.
A non-neoplastic disorder that usually affects postmenopausal women. It is characterized by the leuteinization of ovarian stromal cells. The ovaries are bilaterally involved and enlarged. When it affects women in reproductive age, it causes virilization, high blood pressure, and increased insulin levels.
A carcinoid tumor that arises from the ovary and is characterized by the presence of columnar cells with abundant cytoplasm forming ribbons. The prognosis is excellent.
An embryonal neoplasm arising from the ovary with morphologic features resembling Wilms tumor of the kidney. It occurs during the reproductive age and may present as a rapidly growing adnexal mass.
A yolk sac tumor that arises from the ovary and is characterized by the presence of extensive differentiation into endodermal type glandular structures.
A yolk sac tumor that arises from the ovary and is characterized by the presence of extensive differentiation into hepatic tissue.
A yolk sac tumor that arises from the ovary and is characterized by the presence of multiple dilated spaces lined by cells that resemble mesothelial cells. The dilated spaces coexist with columnar epithelial tissues.
An Oxidation-Reduction Interaction is a non-enzymatic physical interaction between atoms or radicals in which the positive charges on an atom increase (or the negative charges on that atom decrease) while the negative charges on the other atom increase (or the positive charges on that other atom decrease).
Oxidative Regulation involves cellular and biochemical mechanisms that localize and control oxidation/reduction reactions, or that constrain their byproducts, in order to maintain cellular health and homeostasis.
Oxidative Stress Induction involves initiation of activities that induce a disturbance in the pro-oxidant/antioxidant balance, leading to disruption of cell function by superoxide and other free radicals through damage to DNA bases, protein oxidation products, and lipid peroxidation products. Not synonymous with hypoxia or hyperoxia, oxidative stress promotes a range of degenerative disorders.
Reactive oxygen species (ROS) are detrimental to cellular health and can damage biological macromolecules. Electrophilic compounds, xenobiotics and antioxidants are sources of reactive oxygen species, creating oxidative stress that can harm cells. Enzymes involved in the Phase II detoxification of xenobiotics to reduce cellular stress include glutathione transferases, quinone reductase, epoxide hydrolase, heme oxygenase, UDP-glucuronosyl transferases, and gamma-glutamylcysteine synthetase. Expression of these genes protects cells from oxidative damage and can prevent mutagenesis and cancer. Transcription of these enzymes is coordinately regulated through antioxidant response elements (AREs). Nrf2 (NF-E2-related factor 2) and Nrf1 are transcription factors that bind to AREs and activate these genes. Inactive Nrf2 is retained in the cytosol by association a complex with the cytoskeletal protein Keap1. Cytosolic Nrf2 is phosphorylated and translocates into the nucleus in response to protein kinase C activation and Map kinase pathways. In the nucleus, Nrf2 activate genes through AREs by interacting with transcription factors in the bZIP family, including CREB, ATF4 and fos or jun. Nrf2 activation of genes is opposed by small maf proteins, including MafG and MafK, maintaining a counterbalance to Nrf2 and balancing the oxidation level of the intracellular environment. (This definition may be outdated - see the DesignNote.)
A primary endometrioid adenocarcinoma of the endometrium characterized by the presence of eosinophilic malignant glandular epithelial cells.
Compounds that contain Ozone, a highly active oxidizing agent that have application in the treatment of bacterial and viral infections, cancer diagnosis, treatment, and evaluation of disease progression. (NCI)
The disodium salt form of N-phosphonacetyl-L-aspartate (PALA), a pyrimidine antimetabolite with antineoplastic activity. PALA inhibits pyrimidine biosynthesis and increases the extent to which fluorouracil is incorporated into RNA. (NCI04)
A synthetic HIV-1 envelope peptide that was developed for use as a vaccine. Vaccination with PCLUS 3-18MN may stimulate the host immune system to mount cytotoxic T lymphocyte (CTL) and T helper cell responses, and induce the production of neutralizing antibodies. (NCI04)
A synthetic HIV-1 envelope peptide that was developed for use as a vaccine. Vaccination with PCLUS 6.1-18MN may stimulate the host immune system to mount cytotoxic T lymphocyte (CTL) and T helper cell responses, and induce the production of neutralizing antibodies. (NCI04)
A quinazolone compound with anti-tumor activity. PD-168393 is a cell-permeable, irreversible, and selective inhibitor of ligand-dependent epidermal growth factor (EGF) receptor (EGFR). This agent binds to the catalytic domain of EGFR with a 1:1 stoichiometry and inactivates the EGFR tyrosine kinase activity through alkylation of a cystine residue (Cys-773) within the ATP-binding pocket, thereby inhibiting proliferation of EGFR-expressing tumor cells.
A molecular genetic abnormality indicating the presence of a mutation in the PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) gene on chromosome 4q12.
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) is a tissue-specific coactivator that enhances the activity of many nuclear receptors and coordinates transcriptional programs important for energy metabolism and energy homeostasis. Inappropriate increases in PGC-1a activity have been linked to a number of pathological conditions including heart failure and diabetes. PGC-1a is highly expressed in metabolically active tissues including brown fat, skeletal muscle and heart. PGC-1a has been implicated in mitochondrial biogenesis in the heart and increased mitochondrial respiration in brown fat. PGC-1a is a coactivator for many factors including, CBP, Scr-1, PPARa, glucocorticoid receptor, thyroid hormone receptor, several orphan receptors, and MEF2. This pathway illustrates two of the cofactor regulatory factors, MEF2 and PPARa, and an example orphan receptor feedback inhibition loop. Glut4 is used as an example of the downstream elements leading to changes in metabolism. Ichida et al discovered the ERRa repression of PGC-1a. Their results suggest a novel mechanism of transcriptional control wherein ERR-a can function as a specific molecular repressor of PGC-1a. This suggests that other co-activators might also have specific repressors, adding another layer of combinatorial complexity in transcriptional regulation. Czubryt et al identified PGC-1a as a key target of the MEF2/HDAC regulatory pathway and demonstrated this pathway's importance in maintenance of cardiac mitochondrial function. The linking of MEF2/HDAC provides a potential explanation for the increase in mitochondrial number observed in response to CaMK signaling. (This definition may be outdated - see the DesignNote.)
A fusion protein encoded by a t(15;17) translocation, which involves the human genes ZBTB16 and RARA and is characteristic of acute promyelocytic leukemia. It is a transcriptional repressor with both gain-of-function and dominant-negative properties, resulting in transcriptional repression of retinoic acid and non-retinoic acid target genes and culminating in differentiation arrest.
Expression of a fusion protein that results from a fusion of the human genes PML and RARA.
A recombinant fusion protein of the bacterial superantigen Staphylococcal enterotoxin A (SEA) and the variable Fab fragment of the C242 monoclonal antibody. Upon administering PNU-214565, the Fab fragment binds to Lewis antigen, a glycoprotein overexpressed in human colon and pancreatic carcinoma cell surfaces, thereby directing PNU-214565 to the tumor target area and providing tumor specificity. Superantigen staphylococcal enterotoxin A (SEA) promotes the crosslinking of T-cell receptor (TCR) Vb regions with major histocompatibility complex (MHC) class II molecules on antigen presenting cells, thereby enhancing cytotoxic T-lymphocyte activation, cytokine production and tumor cell lysis.
Similar to other nuclear hormone receptors, PPAR acts as a ligand activated transcription factor. Upon binding fatty acids or hypolipidemic drugs, PPARa interacts with RXR and regulates the expression of target genes. These genes are involved in the catabolism of fatty acids. Conversely, PPARg is activated by prostaglandins, leukotrienes, and anti-diabetic thiazolidinediones and affects the expression of genes involved in the storage of the fatty acids. PPARb is only weakly activated by fatty acids, prostaglandins, and leukotrienes and has no known physiologically relevant ligand. However, data from PPARb null mice suggest PPARb does serve a role in fatty acid metabolism and perhaps in skin proliferation and cancer. (This definition may be outdated - see the DesignNote.)
A synthetic form of the ras peptide containing a point mutation at position 12 (glycine to cysteine). Vaccines using mutant ras peptides may be used in the immunotherapy of various cancers that express ras mutations. (NCI04)
A truncated synthetic form of the oncogene Ras, whose protein product p21 is located in the plasma membrane and transduces growth and differentiation signals from activated receptors to protein kinases within the cell. Because mutated Ras proteins may represent highly specific epitopes for T-cell recognition, PR18 (ras-13 Cys) peptide may be used in the vaccine immunotherapy of cancer. (NCI04)
A synthetic form of the ras peptide containing a point mutation at position 13 (glycine to asparagine). Vaccines using mutant ras peptides may be used in the immunotherapy of various cancers that express ras mutations. (NCI04)
A synthetic form of the ras peptide containing a point mutation at position 12 (glycine to valine). Vaccines using mutant ras peptides may be used in the immunotherapy of various cancers that express ras mutations. (NCI04)
A truncated synthetic form of the oncogene Ras, whose protein product p21 is located in the plasma membrane and transduces growth and differentiation signals from activated receptors to protein kinases within the cell. Because mutated Ras proteins may represent highly specific epitopes for T-cell recognition, PR6V10 (ras-12 Asp) peptide may be used in the vaccine immunotherapy of cancer. (NCI04)
A natural or synthetic peptide derived from the Ras protein with potential use in cancer immunotherapy. Ras protein regulates a number of signalling molecules by translocating them to the plasma membrane for activation and may serve as a branchpoint in signal transduction because it orchestrates the activity of multiple signalling pathways to regulate diverse cellular functions. Ras-12 Ala is a mutated form of the wild-type Ras protein in which the amino acid glycine at codon 12 is replaced with alanine. Vaccination with mutated Ras proteins or peptides may stimulate cytotoxic host immune responses to tumor cells that express similarly mutated Ras proteins. (NCI04)
A vaccinia virus carrying a copy of the human gene encoding prostate-specific antigen (PSA), contaminated with bovine viral diarrhea virus (BVDV).
A synthetic peptide based on sequence corresponding to positions 154-163 of the amino acids of prostate-specific antigen (PSA), VISNDVCAQV. Upon administration, PSA:154-163 peptide vaccine may elicit a cytotoxic T-cell response against tumor cells that express PSA.
A 30-residue prostate specific antigen (PSA) oligoepitope peptide (OP) vaccine with potential antineoplastic activity. PSA-OP peptide vaccine contains the PSA-1 and PSA-3 HLA-A2 epitopes and the PSA-9 HLA-class I-A3 epitope joined by peptide linker sequences. In an animal model, vaccination with this agent has been shown to elicit a cytotoxic T-lymphocyte immune response. (NCI04)
PTEN is a tumor suppressor gene. Recombinant PTEN is capable of dephosphorylating phosphatidylinositol 3,4,5-triphosphate[PI(3,4,5)P3], the product of phosphatidylinositol 3-kinase. Many of the cancer-related mutations have been mapped to the phosphatase catalytic domain; it has been suggested that the phosphatase activity of PTEN is required for its tumor suppressor function. The activation of PKB/AKT is regulated in a complex manner via phosphorylation of AKT on Thr308 and Ser473 by PDK1 and ILK (integrin-linked kinase) respectively. Inactivation of PTEN will constitutively activate PKB/AKT pathway. In addition to its role in regulating the PI 3-K/AKT cell survival pathway, PTEN also inhibits growth factor-induced Shc phosphorylation and suppresses the mitogen-activated protein (MAP) kinase signaling pathway. PTEN also interacts with FAK, a key molecule implicated in integrin signaling pathways, and it directly dephosphorylates tyrosine-phosphorylated FAK. PTEN down-regulation of p130CAS through FAK results in inhibition of cell migration and spreading. (This definition may be outdated - see the DesignNote.)
A molecular genetic abnormality indicating the presence of an inactivating mutation in the PTEN gene on chromosome 10q23.
A paclitaxel formulation containing paclitaxel incorporated in biodegradable polyphosphoester (PPE) polymer form with potential antineoplastic activity. Upon intraperitoneal delivery, paclitaxel PPE microspheres slowly and continuously dissolve and deliver paclitaxel to the tumor site, where it binds to tubulin and inhibits the dynamics of disassembly-assembly of microtubules. As a result, this formulation induces cell cycle arrest and leads to cell death.
The molecular events that lead to the perception of pain are a key research field in medicine and drug discovery. The opioid receptors modulate pain signaling in response to endogenous peptide ligands and opiate drugs such as morphine. The kappa opioid receptor plays a key role in the profound analgesia of opiates and is activated by the endogenous peptide ligand dynorphin, encoded by the prodynorphin gene. Production of prodynorphin is transcriptionally regulated by a downstream regulatory element (DRE) in the prodynorphin gene. A transcription factor called DREAM (DRE antagonistic modulator) binds to the DRE and represses prodynorphin transcription when bound. DREAM binds calcium with 4 EF-hand motifs and the binding of DREAM to DNA is repressed in the presence of calcium. Many transcription factors are regulated by calcium indirectly through calcium sensitive kinases and phosphatases, but DREAM is unique to date in being a transcription factor that directly binds calcium and is regulated by calcium binding. DREAM may also regulate other genes such as c-fos. DREAM is expressed in spinal cord neurons in regions involved in pain signaling. The regulation of prodynorphin expression by DREAM also leads to the hypothesis that DREAM is involved in pain signaling. Transgenic mice lacking the DREAM gene were unusually pain insensitive and had elevated spinal levels of dynorphin and tonic activation of the kappa opioid receptor, supporting this hypothesis. Other functions of DREAM may exist such as regulation of presenilins and potassium channel activity in the heart. DREAM is also known as calsenilin and KChIP3 through its association with these other proteins. These processes were not affected in mice lacking the DREAM gene however. (This definition may be outdated - see the DesignNote.)
A non-invasive pancreatic intraductal papillary mucinous neoplasm characterized by the presence of neoplastic epithelial cells that form a single layer and are well polarized. The neoplastic cells exhibit small and uniform nuclei, mild pleomorphism, and rare mitotic figures.
A cystic epithelial neoplasm characterized by the presence of columnar mucin-producing epithelial cells, ovarian-type stroma formation, and a focal or extensive invasive carcinomatous component.
A pancreatic intraductal papillary mucinous neoplasm characterized by the presence of a focal or multifocal invasive carcinomatous component. The invasive carcinoma is either colloid or ductal adenocarcinoma.
A non-invasive or invasive cystic epithelial neoplasm that affects almost exclusively females. It is characterized by the presence of columnar mucin-producing epithelial cells and ovarian-type stroma formation.
A non-invasive pancreatic intraductal papillary mucinous neoplasm characterized by the presence of neoplastic epithelial cells that exhibit loss of polarity, nuclear stratification, hyperchromasia, and pleomorphism. There is severe architectural atypia and frequent mitotic figures present.
A non-invasive malignant cystic epithelial neoplasm arising from the exocrine pancreas. It occurs almost exclusively in women. Small tumors are usually found incidentally. Larger tumors usually produce symptoms related to compression of the adjacent structures. It is characterized by the presence of columnar, mucin-producing epithelial cells which often form papillary projections with irregular branching and budding. There is cellular stratification, severe dysplasia, and high mitotic activity present. Complete surgical removal is usually associated with an excellent prognosis.
A benign or malignant epithelial neoplasm that is usually cystic and arises from the exocrine pancreas. It is characterized by the presence of neoplastic epithelial cells that produce fluid similar to serum. Representative examples include serous cystadenoma and serous cystadenocarcinoma.
A controversial term, used for renal papillary lesions which measure 1cm or less in diameter and contain small, regular nuclei.
An invasive or non-invasive papillary transitional cell carcinoma of the urinary bladder. It is classified as low - or high-grade. -- 2003
A process that involves the non-covalent binding of parathyroid hormone to one of the parathyroid hormone receptors. This interaction plays a role in signal transduction, which mediates the maintenance of calcium and magnesium homeostasis.
Induction or development of an organ or tissue disorder(s) that results from retroviral activity or arises due to the immunocompromised state of an HIV infected individual. (NCI)
Induction or development of a malignant disease(s) or condition(s) that results from retroviral activity or arises due to the immunocompromised state of an HIV infected individual. (NCI)
The pathogenic mechanisms involved in HIV-associated neurological diseases and neurobehavioral dysfunction.
Induction or development of microbe-induced disease(s) in an immunocompromised HIV infected individual.
Any event, process, or activity that produces a deleterious alteration of DNA. (NCI)
Proline-, glutamic acid-, leucine-rich protein 1 (Pelp1 or modulator of nongenomic activity of estrogen, MNAR) is a recently discovered transmitter of estrogen signals. The receptors for estrogen (ER), progestin (PR), androgen (AR) and others are steroid hormone receptors, which are part of a large family of ligand-inducible transcription factors. It has been established that estrogen has at least two courses of action termed classical or genomic and nongenomic. The classical activation cascade is well known. The nongenomic or nontranscriptional activation cascade for the estrogen receptor was determined based on the rapid response times observed for the activation of the MAPK cascade and other cell proliferation effects. The mechanism was believed to involve a membrane bound ER but attempts to isolate such a protein have not been successful. A second possibility would involve a scaffold protein that interacts with ER. Pelp1 appears to fit the second scenario. Pelp1 was first isolated as a coactivator of transcription for ER-alpha. It was observed that Pelp1 was expressed at levels 3-5 times normal in breast tumors. Several breast cancer cell lines have been shown to express Pelp1. Like many nuclear hormone receptors Pelp1 also interacts with Cbp and p300. More recently it has been demonstrated that Pelp1 mediates the interaction of ER and Src leading to the activation of the Mitogen Activated Protein Kinases Erk1 and Erk2. (This definition may be outdated - see the DesignNote.)
A basal cell carcinoma of the penis with an indolent clinical course. It is usually superficial and arises from the shaft and rarely the glans.
The pentose phosphate pathway is a process of glucose turnover that produces NADPH as reducing equivalents and pentoses as essential parts of nucleotides. There are two different phases in the pathway. One is irreversible oxidative phase in which glucose-6P is converted to ribulose-5P by oxidative decarboxylation, and NADPH is generated. The other is reversible non-oxidative phase in which phosphorylated sugars are interconverted to generate xylulose-5P, ribulose-5P, and ribose-5P. Phosphoribosyl pyrophosphate (PRPP) formed from ribose-5P is an activated compound used in the biosynthesis of histidine and purine/pyrimidine nucleotides. This pathway map also shows the Entner-Doudoroff pathway where 6-P-gluconate is dehydrated and then cleaved into pyruvate and glyceraldehyde-3P.
A measure of how well a patient is able to perform ordinary tasks and carry out daily activities.
A neoplastic process characterized by the proliferation of spindle to cuboidal myoepithelial cells around small breast ducts.
Passage or transfer, as of a disease, to a recipient unborn offspring in utero. (NCI)
A class of vaccines with potential antineoplastic activity. Peripheral blood lymphocytes (PBL) are first harvested from a cancer patient and induced to express a particular tumor-associated antigen or multiple antigens. Autologous vaccination with activated PBL may stimulate the host immune system to produce antibodies and/or mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the antigen(s), resulting in decreased tumor growth. (NCI04)
A benign, usually encapsulated slow growing tumor of the peripheral nervous system composed of Schwann cells. It recurs infrequently and only rare cases associated with malignant transformation have been reported.
A gastrointestinal stromal tumor that arises from the peritoneum. This is an extragastrointestinal tumor, meaning that it does not arise directly from the gastrointestinal tract.
Any substance that inhibits phosphatidylinositol 3-kinase (phosphatidylinositide 3-kinase), an enzyme that catalyzes the phosphorylation of the 3 position hydroxyl group of the inositol ring of phosphatidylinositol and functions as an intracellular signal transducer in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. Inhibition of phosphatidylinositol 3-kinase produces antiproliferative and antiangiogenic effects.
Nine currently identified phosphoinositide 3-kinases (PI 3-K) constitute a subfamily of lipid kinases that catalyze the addition of a phosphate molecule on the 3-position of the inositol ring of phosphoinositides. Phosphatidylinositol (PtdIns), the precursor of all phosphoinositides (PI), constitutes less than 10% of the total lipid in eukaryotic cell membranes. Approximately 5% of cellular PI is phosphorylated at the 4-position (PtdIns-4-P), and another 5% is phosphorylated at both the 4- and 5-positions (PtdIns-4, 5-P2). However, less than 0.25% of the total inositol-containing lipids are phosphorylated at the 3-position, consistent with the idea that these lipids exert specific regulatory functions inside the cell, as opposed to a structural function. Here we have chosen to highlight a group of the phosphoinositide targets of the PI3-Ks and their downstream targets. The downstream effects of these PI-3 targets are indicated, illustrating the important role the PI3Ks have in cell function and survival. (This definition may be outdated - see the DesignNote.)
Proposed model for b2-AR- and prostanoid-receptor-mediated PLC and calcium signaling. Receptors coupling to Gs stimulate AC, resulting in elevated cAMP levels and activation of Epac1. Epac1 then catalyses GTP-loading on Rap2B, which leads to PLC-e activation. The proposed pathway may involve additional signaling components to attain PLC stimulation. The action of cAMP seems to be independent of PKA; instead, the cAMP-activated Rap-GEF Epac seems to serve as a cAMP effector, inducing GTP loading and, hence, activation of Rap2B, which then leads to specific activation of PLC-e, which has been shown to interact with Rap GTPases. It is an attractive hypothesis, therefore, that the Rap-dependent PLC and calcium signaling pathway reported here is not restricted to Gs-and AC-coupled receptors, such as the b2-AR and the prostanoid receptor, but could be used by other receptors as well. (This definition may be outdated - see the DesignNote.)
Phospholipase C comes in multiple forms and plays a key role in the signal transduction process for many receptors. Its main function is to hydrolyze phosphatidylinositol diphosphate into diacylglycerol (DG) and inositol triphosphate (IP3). DG is necessary for further activation of Protein Kinase C while IP3 leads to the release of intracellular calcium. (This definition may be outdated - see the DesignNote.)
Phospholipase C (PLC) d1 is a member of the PLC family that produces two second messengers, diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3) by hydrolyzing the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2). DAG in combination with Ca++ is necessary for further activation of Protein Kinase C, while IP3 diffuses into the cytoplasm and mediates the release of intracellular calcium. PLC d1 has a pleckstrin homology (PH) domain that binds to PIP2 in the membrane with an affinity of 1.7 mM. It has selectivity for PIP2 over other phosphatidylinositol lipids and provides a specific probe for activation of PIP2 metabolism to DG and IP3. Activation of PLC d1 results in its translocation from the membrane to the cytoplasm. PLC d1 activity is feedback-inhibited by IP3, which has an 8-fold higher affinity for PLC d1 than does PIP2. The members of the PLC family play a key role in the signal transduction cascade for many receptors. At basal Ca++ levels PLC d1 has been shown to be activated by the adrenoreceptor a1B, adrenoreceptor a1D, a-thromboxane receptor and oxytocin receptor. The G protein involved is the GTP-binding protein known as tissue transglutaminase (Gah or TGII). Gah is a bifunctional enzyme, having GTPase and transglutaminase (TGase) activity and is present in the plasma membrane, cytosol, and nucleus. Exchange of GDP to GTP by Gah is facilitated by activation of the receptors. However, a bimodal regulation of PLC d1 activity has been observed depending on Ca++ levels and occupancy of the guanine nucleotide binding site of Gah. In addition, the GTPase activating protein RhoGAP interacts with and stimulates PLC d1. The complex regulation of PLC d1 activity enables the protein to modulate intracellular signaling. (This definition may be outdated - see the DesignNote.)
Sphingosine-1-phosphate (S1P) is an example of a lipid messenger with both intracellular and extracellular functions. Intracellularly S1P regulates proliferation and survival; extracellularly S1P is a ligand for EDG1 (also known as S1P1). Activation of sphingosine kinase (SPHK), the enzyme that catalyzes the phosphorylation of sphingosine, increases cellular levels of S1P. Inhibitors of SPHK block formation of S1P and inhibit cellular proliferation induced by a variety of factors, including platelet-derived growth factor (PDGF) and PMA. In a study using endothelial cells it was demonstrated that S1P induces activation of alpha-v and B3 integrins via RhoA. S1P also activates Akt via Gi and PI3K. The activated Akt phosphorylates the Edg1 receptor on threonine 236 leading to the activation of Rac1 and subsequent signals leading to actin assembly, chemotaxis and lamellipodia formation. Edg1 stimulation also leads to the activation of the ERK signaling cascade resulting in anti-apoptotic reversal, proliferation and cell survival. (This definition may be outdated - see the DesignNote.)
Modified oligonucleotides in which one of the oxygens of the phosphate group is replaced with a sulfur atom.
Phosphorylation Inhibition involves interference with, or restraint of, the enzymatic creation of a phosphate derivative of an organic molecule; often by transfer of a phosphate group from ATP via the action of a kinase.
An astrocytic tumor of uncertain relation to pilocytic astrocytoma. It occurs predominantly in infants and young children. It is characterized by a monomorphic architectural pattern, usually associated with the absence of Rosenthal fibers and eosinophilic granular bodies. The clinical course is usually aggressive.
The hydrochloride salt form of pimonidazole, a hypoxia-selective 2-nitroimidazole with potential radiosensitizing activity. Pimonidazole is reduced in hypoxic environments such as those found in tumors. In hypoxic cells and tumors, reduced pimonidazole binds to thiol-containing proteins and glutathione. The resulting complexes accumulate in hypoxic tumors, deplete radioprotective thiol compounds, and cause the tumor to be more susceptible to radiation treatment.
Any substance that inhibits S-adenosyl-methionine decarboxylase, an enzyme involved in the biosynthesis of the polyamines spermidine and spermine. Polyamines are essential for cell division, cell differentiation and membrane function and inhibition of S-adenosyl-methionine decarboxylase results in inhibition of cell growth and differentiation.
Severe Acute Respiratory Syndrome (SARS) has affected thousands of individuals, causing fever, and pneumonia with a mortality rate estimated at 10-18%. Human coronaviruses cause mild respiratory illness and account for about a third of all cases of the common cold. A novel coronavirus has been identified as the causative agent of SARS and its genome has been sequenced. The enveloped SARS virus contains a large plus strand RNA genome, approximately 30,000 nucleotides. Examination of the SARS coronavirus sequences reveals that the rep gene covers over 20,000 nucleotides and encodes two overlapping polyproteins cleaved by viral proteases into smaller protein products. Translation of the longer polyprotein encoded by the rep gene requires a ribosomal frameshift. Other viral genes are predicted to encode the transmembrane spike protein S involved in viral fusion with host cells, the envelope protein E, the membrane protein M and the nucleocapsid protein N that binds to the RNA genome as well as several additional open reading frames with unknown functions. Viral entry into the cell is followed by translation of the viral rep gene, which codes for a viral protease within the polyprotein, Mpro or 3CLpro. The SARS 3CLpro has also been verified in vitro to cleave after the Gln residue at Leu-Gln-(Ser, Ala, Gly). Polypeptides released from the polyproteins by the main viral protease Mpro or 3CLpro include the viral polymerase and a protease. Both products are essential for viral replication and transcription. Structural crystals of a porcine coronavirus protease with a transition state inhibitor suggest that inhibitors of the distantly related rhinovirus protease like the drug AG7088 may be modified to produce drugs that block the SARS protease and viral replication. Blocking entry of the SARS virus into cells, involving recognition of cellular receptors by the S spike protein, may provide another strategy for the development of drugs to treat SARS. (This definition may be outdated - see the DesignNote.)
An retroviral vector encoding human IL-2 with potential antineoplastic property. SBIL-2 (Surgery Branch IL-2) can be used to transfect tumor infiltrating lymphocytes, which can then be re-introduced back to cancer patients, thereby stimulate T cell activation and immunopotentiation responses.
A humanized monoclonal antibody targeting the CD40 antigen with potential antineoplastic activity. CD-40, an integral membrane protein found on the surface of B lymphocytes and member of the tumor necrosis factor receptor super-family, is highly overexpressed on the cell surface of a number of B-cell malignancies. Monoclonal antibody SGN-14 specifically binds to and inhibits CD-40, thereby inhibiting cell proliferation and inducing cell lysis via antibody-dependent cellular cytotoxicity (ADCC) in cells.
A substance composed of a monoclonal antibody-enzyme fusion protein (SGN-17), containing a cloned binding region of the L49 monoclonal antibody and the enzyme beta-lactamase, and an inactive prodrug form of Mephalan (SGN-19) used in Antibody Directed Enzyme Therapy (ADEPT). (NCI)
A pyrrolobenzodiazepine dimer with potential antineoplastic activity. SJG-136 binds to the minor groove of DNA and induces interstrand cross-links between two N-2 guanine positions, thereby inhibiting DNA replication and transcription. With a preference for binding to purine-GATC-pyrimidine sequences, SJG-136 adducts do not appear to be subject to p53-mediated DNA excision repair mechanisms. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=415963&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=415963&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C29435"" NCI Thesaurus)
The tumor necrosis factor (TNF) receptor superfamily contains several members with homologous cytoplasmic domains known as death domains (DD). The intracellular DD are important in initiating apoptosis and other signaling pathways following ligand binding by the receptors. In the absence of ligand, DD-containing receptors are maintained in an inactive state. TNFR1 contains a cytoplasmic DD required for signaling pathways associated with apoptosis and NF-kB activation. Jiang et al. identified a widely expressed 60 kDa protein, named SODD (silencer of death domains), associated with the DD of TNFR1 and DR3. Overexpression of SODD suppresses TNF-induced cell death and NF-kB activation demonstrating its role as a negative regulatory protein for these signaling pathways. TNF-induced receptor trimerization aggregates the DD of TNFR1 and recruits the adapter protein TRADD. This in turn promotes the recruitment of the DD-containing cytoplasmic proteins FADD, TRAF2, and RIP to form an active TNFR1 signaling complex. In contrast, SODD acts as a silencer of TNFR1 signaling and does not interact with TRADD, FADD, or RIP. It is associated with the DD of TNFR1 and maintains TNFR1 in an inactive, monomeric state. TNF-induced aggregation of TNFR1 promotes the disruption of the SODD-TNFR1 complex. SODD does not interact with the DD of other TNF receptor superfamily members such as Fas, DR4, DR5, or TNFR2. SODD association with TNFR1 may represent a general model for the prevention of spontaneous TNF signaling by other DD-containing receptors. (This definition may be outdated - see the DesignNote.)
Progression through the cell cycle is accompanied by activation of the proto-oncogene c-Src, a protein tyrosine kinase. Overexpression of Src leads to tyrosine phosphorylation of multiple protein substrates and cellular transformation. During interphase the Src protein folds back upon itself to stay in the inactive state, with a phosphotyrosine residue in one domain at Tyrosine 529 bound by an SH2 domain in the same protein. Activation of c-Src involves protein-tyrosine phosphatase alpha (PTP-alpha, or RPTP-alpha), a transmembrane protein with a cytoplasmic phosphatase domain. A variety of evidence has indicated that PTP-alpha dephosphorylates c-Src at Tyr529, allowing Src to open up and become activated, and that this activation occurs in association with mitosis. To activate Src, PTP-alpha must first open up the folded Src through binding itself to the phosphorylated Src domain, a process blocked by binding of Grb-2 to PTP-alpha at phosphorylated Tyr789. PTP-alpha phosphorylated at Tyr789 also binds to the Src SH2 domain, causing the Src structure to open at Src Tyr529 to become available for dephosphorylation. During mitosis the mitotic kinase Cdc-2 phosphorylates Src, along with other cellular substrates, and in so doing makes Src more prone to PTP-alpha dephosphorylation and activation. The activity of PTP-alpha toward Src is also regulated by phosphorylation of PTP-alpha by protein kinase C at serines 180 and 204, releasing the inhibition of PTP-alpha by Grb-2. In the normal cell cycle, Src activity is down-regulated after cell division through dephosphorylation by protein phosphatases and phosphorylation by Csk (C-terminal src kinase) and PTP-alpha dephosphorylation returns the cycle to its interphase condition. The regulation of Src activity during mitosis demonstrates how protein phosphorylation can shift the delicate equilibrium of molecular interactions and cellular responses. (This definition may be outdated - see the DesignNote.)
Serum response factor (SRF) is a transcription factor, which binds to a serum response element (SRE) associated with a variety of genes including immediate early genes such as c-fos, fosB, junB, egr-1 and -2, neuronal genes such as nurr1 and nur77, and muscle genes such as actins and myosins. By regulating expression of these genes, SRF controls cell growth and differentiation, neuronal transmission, as well as muscle development and function. SRF can be activated by serum, lysophosphatidic acid (LPA), lipopolysaccharide (LPS), 12-O-tetradecanoylphorbol-13-acetate (TPA), cytokines, tumor necrosis factor-alpha (TNFalpha), agents that increase intracellular Ca2+, T-cell virus1 activator protein, hepatitis B virus activator proteins pX, activated oncogenes and protooncogenes, and extracellular stimuli such as antioxidant and UV light. In serum-starved cells, MAL is predominantly cytoplasmic where it is sequestered by actin monomers. Upon serum stimulation, Rho becomes active and, through its interaction with ROCK and mDia1, causes an accumulation of F-actin and a commensurate decrease in the level of G-actin. As a consequence, MAL is no longer sequestered and is free to translocate to the nucleus where it associates with SRF and activates SRE-mediated gene expression. (This definition may be outdated - see the DesignNote.)
A vaccine comprised of a synthetic Sialyl-Tn antigen linked to the protein carrier, keyhole limpet hemocyanin (KLH), administered with immunostimulant, Detox. Vaccination with STn-KLH plus Detox may elicit an IgG-based anti-STn antibody response and ultimately a cytotoxic T-cell response against STn-expressing cancer cells.
A combination preparation of the nonsteroidal anti-inflammatory drug salicylic acid and the inorganic compound sulfur with keratolytic activity. Salicylic acid and sulfur loosen and shed dead cells, thereby preventing skin pores from clogging up. This combination treats acne, dandruff and several other skin and scalp disorders.
A carcinoma that arises from a pleomorphic adenoma in the salivary glands. It usually originates in the parotid gland. Patients usually present with a history of a long-standing tumor mass which grew rapidly in the past few months. Patients with non-invasive or minimally invasive carcinoma have an excellent prognosis. In cases where there is invasion of the surrounding tissues, the clinical course is aggressive.
A benign or malignant tumor that arises from the salivary glands. It is characterized by the presence of neoplastic cells with myoepithelial differentiation. This category includes benign myoepithelioma and myoepithelial carcinoma.
A benign, slow-growing tumor composed of cells that demonstrate both epithelial and mesenchymal differentiation. It is the most common neoplasm of salivary gland origin, and mostly occurs in the parotid gland. The average age of patients has been reported to be 43 years; women are more often affected than men. The malignant change rate has been estimated to be 6%. The malignant counterpart is carcinoma ex pleomorphic adenoma.
A microscopic finding indicating the presence of cells with sarcomatoid, usually spindle cell differentiation in a tumor sample.
A rare, aggressive variant of intrahepatic cholangiocarcinoma. It is characterized by the presence of adenocarcinoma cells that are intermingled with malignant pleomorphic spindle cells.
Peeling skin patches. Causes include psoriasis, eczema, and sunburns.
A rare type of mucoepidermoid carcinoma of the thyroid gland, usually associated with chronic lymphocytic thyroiditis. It exhibits a unique morphologic appearance consisting of a squamoid, nested growth pattern, dense fibrosis, and mucinous differentiation. The histogenesis of this unusual carcinoma has been debated, and it is unclear if it arises from remnants of the ultimobranchial body or from the follicular epithelial cells.
A very rare breast adenocarcinoma with sebaceous differentiation.
A glioblastoma arising from a lower grade astrocytoma. It is more commonly seen in younger patients and is associated with IDH1 or IDH2 gene mutations.
A transitional cell carcinoma that has spread to the prostate gland directly from the bladder.
The trihydrochloride salt of the anthrapyrazole antineoplastic antibiotic sedoxantrone with potential antineoplastic activity. Sedoxantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis.
In most animal species, the anteroposterior body axis is generated by the formation of repeated structures called segments. In vertebrate segmentation, a specialized mesodermal structure called the somite gives rise to skeletal muscles, vertebrae, and some dermis. Formation of the somites is a rhythmic process that involves an oscillator, the segmentation clock, driven by Wnt and Notch signaling. The clock ticks in somite precursors and halts when they reach a specific maturation stage defined as the wavefront, established by FGF and Wnt signaling. Lunatic fringe was shown to act downstream of Notch and to bind and negatively regulate its own promoter. Another cyclic gene is hes1. It acts also downstream of Notch and codes for an unstable protein able to negatively regulate its own promoter too. (This definition may be outdated - see the DesignNote.)
Agents that selectively bind to estrogen receptors on breast cancer cells and stop estrogen-dependent cell proliferation. (NCI)
An extremely rare adenocarcinoma that arises from the seminal vesicle.
A rare benign cystadenoma that arises from the seminal vesicle.
The fruit of Cassia acutifolia and Cassia angustifolia (Cassia) with laxative and purgative activities. The active ingredients in senna fruit include the hydroxyanthracene glycosides sennosides A and B (rhein dianthrones) and sennosides C and D (rhein aloe-emodin heterodianthrones). Sennosides irritate the bowel lining and stimulate the bowel muscular coat, particularly in the colon, resulting in accelerated bowel transit and evacuation.
Serine/Threonine Phosphorylation involves covalent linkage of a phosphate group (from a donor compound such as ATP) with a serine or threonine residue of a Protein Kinase acceptor, often as a mechanism of kinase activity regulation.
Any expected or unexpected adverse event, related or unrelated to the intervention, occurring at any agent dose, any phase of product or procedure testing, that results in any of the following outcomes: death, a life-threatening adverse event, requires inpatient hospitalization (not required as part of the treatment) or prolongation of existing hospitalization, a persistent or significant disability or incapacity, or cancer, or a congenital anomaly or birth defect. Important medical events that may not result in the listed outcomes may be considered as serious when, based upon appropriate medical judgment, they represent significant hazards or potentially serious harm to the research subject or others and may require medical intervention to prevent one of the outcomes listed in this definition.
By induction of conjugation, transport, and/or oxidation, Serotonin Degradation consists of breakdown of a secreted biochemical messenger and regulator (serotonin) synthesized from L-Tryptophan that mediates neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity through multiple receptor families on specific target cells.
A process that involves the binding of serotonin to the serotonin receptor. These interactions are involved in regulation of mood, appetite, sleep, muscle contraction and some cognitive functions including memory and learning.
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activites of daily living.
An ovarian sex cord-stromal tumor characterized by the presence of Sertoli cells forming annular tubules. It may be associated with Peutz-Jeghers syndrome. Cases associated with Peutz-Jeghers syndrome have followed a benign clinical course. Cases which are not associated with Peutz-Jeghers syndrome have been reported having a clinically malignant course.
A monoclonal antibody directed against a specific tumor-associated antigen (TAA). (NCI04)
A murine monoclonal anti-idiotype antibody that targets human B-cell lymphomas with potential antineoplastic activity. Shared Anti-Id-Ab-S006 binds to antigens on neoplastic B cells, resulting in tumor cell destruction by the reticuloendothelial system or cytotoxic T lymphocytes (CTL). (NCI04)
A murine monoclonal anti-idiotype antibody with potential antineoplastic activity. Shared anti-id-Ab-S024A binds to tumor-associated antigens (TAAs) on the surface of neoplastic cells resulting in tumor cell destruction by the reticuloendothelial system or cytotoxic T lymphocytes (CTL).
The differentiation of muscle cells is regulated by many factors, including the MyoD/MEF2 family of transcription factors. The MyoD/MEF2 dimer binds to promoters to activate genes involved in muscle cell differentiation. One of the factors that regulates the role of MyoD/MEF2 in myogenesis is the protein MEF2-interacting transcription repressor (MITR), a transcriptional repressor. When MITR is bound to MEF2, myogenesis genes are repressed rather than being activated. The transcriptional repression by MITR occurs in part at least through interaction with the CtBP (carboxy-terminal binding protein) corepressor. The inhibitory activity of MITR is itself regulated by the calmodulin dependent protein kinase CAMK. When CAMK is activated by factors such as IGF-1, it phosphorylates two specific residues in MITR, ser218 and ser448. Phosphorylated MITR does not bind to MEF2, but does bind to the protein 14-3-3, helping to block the repression of myogenesis. CAMK also plays a role in myogenesis through phosphorylation of histone deacetylase (HDAC), in which HDAC alters chromatin to repress myogenesis. Like MITR, phosphorylation of HDAC removes the repression, allowing myogenesis to continue. MITR shares sequence homology with HDAC, but itself lacks the enzyme motif. (This definition may be outdated - see the DesignNote.)
Signal induction is the intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (e.g., hormone, neurotransmitter, etc.) is transferred to a receptor molecule through a physical binding interaction that alters the conformational and functional state of the receptor molecule and promotes an alteration in cell function.
Repression of any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals.
A substance that inhibits kinase enzymes and other proteins involved in signal transduction pathways to prevent tumor cell growth and induce apoptosis.
An intrahepatic cholangiocarcinoma characterized by the presence of signet ring adenocarcinoma cells.
A microscopic finding indicating the invasion of sinusoidal spaces by malignant cells.
The process by which normal skin cells are transformed into cancer cells.
A small (less than 5-10 mm) elevation of skin that is non-suppurative.
An enteropathy-associated T-cell lymphoma arising from the small intestine, most commonly the jejunum or ileum. Patients usually present with abdominal pain, often associated with intestinal perforation. There is often a history of celiac disease. The lymphoma cells are usually medium-sized to large and form an ulcerating mucosal lesion with invasion of the small intestinal wall. Villous atrophy is present in the adjacent small intestinal mucosa. In a minority of cases the lymphoma cells are medium-sized and form a monomorphic infiltrate.
A record of an individual's background in regard to smoking tobacco. This would include such factors as start date, end date (if applicable), number of cigarette smoked, attempts to quit, and others.
A process that involves the binding of a neurotransmitter to a ligand-gated sodium channel protein. This interaction plays a role in the regulation of signaling pathways that mediate muscle cell depolarization.
Sonic Hedgehog (Shh) is one of a family of three secreted proteins, including Indian Hedgehog (Ihh) and Desert Hedgehog (Dhh), that play distinct and crucial roles in development. The morphogenic signal Shh provides in the developing CNS induces proliferation of neuronal precursor cells in the developing cerebellum and other tissues. Proliferative signaling by Shh is involved in the development of cancer, including specific brain and skin cancers such as basal cell carcinomas, while activation of Shh signaling in neurons may also provide a means to induce neuronal regeneration. Mitogenic Shh signaling does not appear to involve Map kinase pathways, but may involve induction of Cyclin D1 expression to maintain Rb in the hyperphosphorylated state and allow progression through the G1 phase of the cell cycle. Activation of myc may be one mechanism by which Shh induces cell cycle progression. Activation of Shh proliferative signaling occurs through binding to a receptor complex including Patched (Ptc-1) and Smoothened, a G-protein coupled receptor. Patched is an integral membrane protein with twelve transmembrane domains that acts as an inhibitor of Smoothened activation. Patched has been classified as a tumor suppressor due to its inhibition of Smoothened and the presence of inactivated Ptc-1 mutations in some cancers. One possibility is that Ptc-1, which resembles transmembrane channels, may not directly associate with Smoothened but may repress Smoothened signaling by transporting an endogenous Smoothened inhibitor across the plasma membrane into the cytoplasm. Small non-peptide agonists and antagonists of the Shh pathway have been identified and appear to act at the level of the Smoothened receptor, providing pharmacological tools to study Shh signaling. The pathway downstream of the Smoothened receptor has remained somewhat unclear, but involves the Gli family of transcriptional activators, including Gli-1, Gli-2, and Gli-3, homologs of the drosophila gene cubitis interruptis. Kinases including GSK-3 and PKA oppose activation of the Shh pathway, perhaps by regulating the stability of Shh pathway intermediate signaling factors transcription factors. Suppressor of Fused (SUFU) interacts directly with Gli proteins, repressing Shh signaling while Dyrk1 is a kinase that acts by a distinct pathway to stimulate Gli1 activation of transcription. The multiplicity of factors involved in Shh signaling creates many opportunities for therapeutic intervention in the treatment of cancer and possibly neurodegenerative diseases. (This definition may be outdated - see the DesignNote.)
The transcriptional regulator CREM plays a key role in spermatogenesis, acting as a central transcription factor triggering a cascade of transcriptional activation of post-meiotic genes involved in this process such as calspermin and testis angiotensin-converting enzyme. The key role of CREM in sperm formation is demonstrated by the male sterility of mice lacking CREM, the failure of spermatids to develop into mature sperm, and a lack of post-meiotic gene expression in these animals. Prior to meiosis, splice variants of CREM act as antagonists of cAMP-dependent transcriptional activation, but coordinate with spermatogenesis, the potent transcriptional activator CREM tau splice variant is highly expressed. In other tissues CREM activates genes in response to cAMP through phosphorylation and CBP association, but transcriptional activation by CREM in male germ cells is CBP independent. Stimulation of spermatids with follicle-stimulating hormone (FSH) induces cAMP formation, and the association of CREM with the coactivator ACT, although the mechanism regulating the interaction of CREM with ACT is not yet known. A two-hybrid screen looking for ACT interacting factors revealed another surprising component regulating CREM, the kinesin Kif17b. Kinesins are molecular motors that interact with microtubules to transport organelles and other material within the cell. Kif17b is actively exported from the nucleus in a Crm1-dependent manner, so when it is bound to ACT the export of Kif17b excludes CREM-ACT from the nucleus and blocks transcriptional activation by this complex. The mechanism regulating the interaction of Kif17b with ACT to drive CREM activation is not yet known. Although the regulation of transcription by a kinesin is surprising, a functional connection between cytoskeletal elements and transcriptional regulation is not unprecedented, as demonstrated by the transcription factor MIZ-1 that regulates transcription in response to changes in microtubule structure. (This definition may be outdated - see the DesignNote.)
Spindle Assembly Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction with the mitotic spindle that can affect spindle function and mitosis.
While transcriptional regulation is often viewed as the most prevalent way extracellular signals act to regulate gene expression, post-transcriptional regulation of splicing, RNA stability, and translation are also regulated by extracellular signals. Sam68, a member of a family of RNA-binding proteins called STAR proteins, mediates alternative splicing in response to extracellular signals, such as altered splicing of CD44 in response to phorbol ester treatment of T cells. RNA binding and activity of SAM68 is regulated by upstream signals through phosphorylation and modulating of its interaction with other proteins, itself, and with RNA. Phorbol ester treatment of T cells stimulates the ras/ Map kinase pathway, activating Erk and phosphorylation of Sam68, inducing alternative splicing of CD44 and perhaps other cellular RNA targets. Sam68 is localized in the nucleus to a specific substructure called the Sam68/SLM Nuclear Bodies, colocalizing with splicing factors and helping to link signal transduction with RNA processing. Sam68 has been suggested to play a role in a variety of pathways, including insulin signaling and HIV gene expression, substituting for the activity of viral Rev protein, and being regulated by arginine methylation as well as phosphorylation. In addition to the role of Sam68 regulating posttranscriptional gene expression, Sam68 also interacts with transcription factors such as CBP and appears to regulate gene expression. Sam68 also appears to play a role in cell cycle progression through influencing RNA processing. During mitosis SAM68 is tyrosine phosphorylated and associated with Src. The interaction of Sam68 with RNA is repressed by this phosphorylation, whereas interaction of Sam68 with Ras-GAP is stimulated by phosphorylation. Sam68 appears to be downregulated in tumors and transformed cells and its expression is reduced during mitosis, suggesting it inhibits proliferation. The RNA binding domain in Sam68, called a KH domain, is absent in a splice isoform that is expressed in cells that display contact inhibition of cellular growth. Sam68 with the KH domain appears in some settings to stimulate the G1/S transition, while blocking mitosis in some reports. (This definition may be outdated - see the DesignNote.)
Any change in the DNA sequence of a breast tumor susceptibility gene that is not found in the parental samples.
A squamous cell carcinoma that arises from the breast parenchyma and is characterized by cellular discohesion resulting in a pseudoangiosarcomatous pattern.
A squamous cell carcinoma that arises from the breast parenchyma and is characterized by the presence of large malignant cells that exhibit keratinization.
A squamous cell carcinoma that arises from the breast parenchyma and is characterized by the presence of spindle-shaped malignant cells.
A microscopic finding indicating the presence of cells with squamous differentiation in a tumor sample.
Stage III NHL means involvement of lymph node regions on both sides of the diaphragm (III) that may also be accompanied by localized involvement of an extralymphatic organ or site (IIIE), by involvement of the spleen (IIIS), or both (IIIS+E). (from PDQ)
Stage II NHL means involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph nodes with or without other lymph node regions on the same side of the diaphragm (IIE). Note: The number of lymph node regions involved may be indicated by a subscript (e.g., II3). (from PDQ)
Any substance that inhibits topoisomerase-II, a topoisomerase that relieves torsional stress in a DNA molecule by cutting both strands of the DNA double helix. A topoisomerase II inhibitor can either stabilize the DNA-protein complex or inhibit the catalytic activity of the enzyme. Inhibition of topoisomerase-II causes DNA damage, inhibition of DNA replication, and apoptosis.
Any substance that inhibits topoisomerase-IV, a bacterial topoisomerase that works by cutting both strands of the DNA double helix. Inhibition of topoisomerase-IV causes DNA damage, inhibition of DNA replication, and cell death.
Topoisomerase Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction and spatial complementarity with enzymes that change the degree of supercoiling in DNA by cutting one or both strands. Type I topoisomerases cut only one strand of DNA, while type II topoisomerases cut both strands of DNA.
The PML nuclear bodies are ring-shaped nuclear substructures associated with the regulation of transcription, transformation, cell growth, and apoptosis and are characterized by the presence of the protein PML. The activities of PML as a tumor suppressor and apoptosis inducing factor are exerted through the numerous proteins it interacts with in the PML-nuclear bodies including the tumor suppressor p53. DNA damage-induced activation of p53-dependent apoptosis requires PML. PML acts as a coactivator for p53 and increases acetylation of p53 by the transcriptional coactivator CBP. This acetylation of p53 is reversed by the deacetylase SirT1, the human homolog of the yeast gene Sir2, and this deacetylation opposes the transcriptional activation of p53. The tumor suppressor Rb also interacts with the PML nuclear body, increasing transcriptional repression of genes involved in cell cycle progression, suggesting that PML may affect cellular transformation through more than one mechanism. PML interacts directly with Ubc9, which modifies PML through the attachment of the ubiquitin-like peptide Sumo-1. Sumo-1 modification of PML is not necessary for the nuclear bodies to form, but may affect the recruitment of proteins that interact with PML. PML is involved in non-p53 mediated apoptotic pathways, such as DAXX-mediated apoptosis induced by Fas and TNF and regulates the transcriptional repressor activity of Daxx. The sequestration of Daxx by the PML nuclear bodies relieves the repression of other transcription factors like Pax3 by Daxx. Tumor suppression by PML may in general involve the formation of specific regulatory transcription complexes, including those with DAXX, p53 and CBP. Factors that affect the assembly of PML into the PML nuclear bodies affect the proliferation and transformation of cells. Viral early proteins can interact with PML to disrupt the nuclear bodies, allowing increased proliferation of cells and reduced apoptosis, good conditions for DNA virus infection. Another factor that disrupts the formation of PML nuclear bodies is a translocation between the PML and RAR-alpha genes found in acute promyelocytic leukemia (APL) patients. Binding of retinoic acid to the RAR-alpha steroid hormone receptor activates transcription of retinoic-acid responsive genes. The translocation found in APL patients creates two chimeric proteins, RARalpha-PML and PML-RARalpha. Retinoic acid given to APL patients causes the reappearance of nuclear bodies, and the reversal of cellular transformation, affecting a cure for these patients. (This definition may be outdated - see the DesignNote.)
An account of all experiences related to the receipt of blood, WBC, platelets, and/or other blood components.
Any subcellular or molecular process involved in translocation of a biological entity, such as a macromolecule, from one site or compartment to another.
Any of the commercial combination preparations, by Novartis, containing the antihistamine chlorpheniramine maleate and the decongestant pseudoephedrine hydrochloride, either alone or in combination with the analgesic antipyretic acetaminophen and/or the antitussive dextromethorphan hydrobromide. Chlorpheniramine maleate, an antihistamine, blocks the effects of histamine, thereby preventing symptoms such as sneezing and itchy, watery eyes, runny nose and sore throat. Pseudoephedrine hydrochloride, a sympathomimetic agent, acts as a decongestant by inducing vasoconstriction mediated via alpha-adrenergic receptors. This reduces blood flow, decreases swelling and prevents nasal and sinus congestion.
An orally-active synthetic hydrochloride salt form of swainsonine, an inhibitor of Golgi alpha-mannosidase II. Tridolgosir inhibits formation of carbohydrate structures affecting cell-cell adhesion, resulting in decreases in tumor growth or metastasis. This agent also stimulates the immune system. (NCI04)
A chromosomal abnormality consisting of the presence of a third copy of chromosome 4 in somatic cells.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 5 in somatic cells.
Nerve growth factor (NGF) is a neurotrophic factor that stimulates neuronal survival and growth through TrkA, a member of the trk family of tyrosine kinase receptors that also includes TrkB and TrkC. Some NGF responses are also mediated or modified by p75LNTR, a low affinity neurotrophin receptor. Binding of NGF to TrkA stimulates neuronal survival, and also proliferation. Pathways coupled to these responses are linked to TrkA through association of signaling factors with specific amino acids in the TrkA cytoplasmic domain. Cell survival through inhibition of apoptosis is signaled through activation of PI3-kinase and AKT. Ras-mediated signaling and phospholipase C both activate the MAP kinase pathway to stimulate proliferation. (This definition may be outdated - see the DesignNote.)
The tubby gene product is expressed in the brain and has been implicated by mouse genetics in obesity and other disorders such as blindness. Structural analysis predicts that this gene acts as a transcription factor, binding to DNA to regulate gene expression. More recently, it was reported that tubby binds to phosphoinositides in the plasma membrane, helping to localize this factor in the membrane region in the absence of pathway activation. Tubby also interacts with Gq-alpha g-protein subunits, localizing tubby to regions of g-protein activation. Activation of phosphatase C activity and hydrolysis of membrane phosphoinositides leads to release of tubby from the plasma membrane, allowing tubby to enter the nucleus to bind DNA and regulate transcription. Some G-protein coupled receptors such as 5-HT2c may signal in part through tubby in addition to calcium-mediated pathways and protein-kinase signaling pathways. The identity of genes regulated by tubby and the mechanism by which tubby affects obesity remain to be explored. (This definition may be outdated - see the DesignNote.)
A rare, typically benign ovarian neoplasm composed of Sertoli cells. Patients may present with pseudoprecocity, menometrorrhagia, amenorrhea, hirsutism, and hoarseness. Rarely it may invade the ovarian stroma and extend beyond the ovary.
Any agent that binds to tubulin molecules and interferes with the microtubule assembly and disassembly dynamic. A tubulin binding agent impedes cell division and can be used to treat a variety of cancers.
An event, process, or condition that supports, or results from, tumor development.
Proliferation of blood vessels in a tumor.
Any type of motility of a tumor cell that involves translocation of the cell, or cell body, from one site to another; distinct from forms of cell movement that involve only movement of cell processes (e.g., axons, microvilli, etc.). (NCI)
A mixture of allogeneic or autologous tumor cells and bacillus Calmette-Guerin (BCG) in a liquid vehicle with potential antineoplastic activity. Vaccination of the host with tumor cell vaccine plus BCG may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against similar host tumor cells, resulting in decreased tumor growth. The BCG component serves as an adjuvant, a nonspecific stimulator of the immune response. (NCI04)
Growth of a tumor involving either an increase in size of a continuous tumor tissue mass or translocation of tumor cells to secondary sites. (NCI)
Mechanisms that prevent immune detection and elimination of tumor cells
The loss of a fluid from a tumor. This can occur under normal circumstances or during biopsy or other surgical procedure.
A recombinant form of endogenous Tumor Necrosis Factor alpha manufactured by Knoll Pharmaceuticals. Tumor necrosis factor-alpha binds to and activates receptors on the cell surface, resulting in modulation of adipocyte metabolism, lysis of tumor cells, and induction of hemorrhagic necrosis of certain transplantable tumors. (NCI04)
The second step in two-stage carcinogenesis: the conversion of an initiated (premalignant) cell to malignancy.
Tumor suppression involves inhibition of tumor cell growth, proliferation, malignancy, or metastasis.
A recombinant form of endogenous Tumor Necrosis Factor alpha. Tumor necrosis factor-alpha binds to and activates receptors on the cell surface, resulting in modulation of adipocyte metabolism, lysis of tumor cells, and induction of hemorrhagic necrosis of certain transplantable tumors. (NCI04)
A recombinant form of endogenous Tumor Necrosis Factor alpha manufactured by Genzyme Pharmaceuticals. Tumor necrosis factor-alpha binds to and activates receptors on the cell surface, resulting in modulation of adipocyte metabolism, lysis of tumor cells, and induction of hemorrhagic necrosis of certain transplantable tumors. (NCI04)
A rare neoplasm arising from specialized prostatic stroma. This category includes prostatic stromal proliferations of uncertain malignant potential and prostatic stromal sarcomas.
A sex cord-stromal tumor that arises from the ovary or the testis. Representative examples include fibroma, fibrosarcoma, and thecoma.
A measurement of the tumor-producing/cancer cell-producing potency of an agent. The carcinogenicity value is usually expressed as milligrams of agent administered per tumor developed.
An autosomal dominant hereditary neoplastic syndrome caused by mutations in the PMS2, MLH1, or MSH2 genes. It is characterized by the presence of glioblastoma and the absence of familiar adenomatous polyposis. Patients often develop hereditary nonpolyposis colorectal carcinoma.
An autosomal dominant hereditary neoplastic syndrome caused by mutations in the APC gene. It is characterized by the presence of medulloblastoma and familiar adenomatous polyposis.
A rare, primary immunodeficiency with an autosomal dominant pattern of inheritance but variable penetrance. It is the most common subtype of autoimmune lymphoproliferative syndrome (ALPS). It is usually caused by a germline mutation in the Fas gene that leads to defective Fas-induced apoptosis but in a minority of cases, it also may be attributed to a somatic Fas mutation. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.
A rare, primary immunodeficiency with an autosomal dominant pattern of inheritance but incomplete penetrance. It is caused by a mutation in the FASLG (Fas ligand) gene that leads to defective Fas-induced apoptosis. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.
A rare, primary immunodeficiency with an autosomal dominant pattern of inheritance but incomplete penetrance. It is caused by a mutation in the CASP10 (caspase-10) gene that leads to defective Fas-induced apoptosis. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.
A rare, primary immunodeficiency. It is caused by a currently undetermined defect in the Fas-induced apoptosis pathway. No mutations in Fas, FASLG or CASP10 are detectable. Disruption of Fas-induced apoptosis impairs lymphocyte homeostasis and immune tolerance. Characteristic laboratory findings include an increase in circulating, double-negative (CD4-/CD8-) T cells in the setting of immune-mediated anemia, thrombocytopenia and neutropenia. Clinical signs present in childhood include fatigue, pallor, bruising, hepatosplenomegaly and chronic, non-malignant, non-infectious lymphadenopathy. The clinical course is influenced by a strong association with other autoimmune disorders and an increased risk for developing Hodgkin and non-Hodgkin lymphoma.
A classification of primary endometrial adenocarcinomas that refers to clear cell adenocarcinoma, serous adenocarcinoma, and serous endometrial intraepithelial carcinoma.
A classification of primary endometrial adenocarcinomas that refers to endometrioid adenocarcinoma and mucinous adenocarcinoma.
An ovarian thecoma characterized by the presence of cells with uniform nuclei and abundant vacuolated cytoplasm. Mitoses are not present or, when present, are rare.
A recombinant peptide consisting of amino acid residues 240 to 251 of the enzyme tyrosinase, a protein frequently expressed by melanoma cells, with serine substitution at position 244 to improve immunogenicity. Vaccination with tyrosinase:240-251(244S) may stimulate the host immune response to mount a cytotoxic T lymphocyte (CTL) response against tyrosinase-expressing tumor cells.
Any substance that inhibits tyrosine 3-monooxygenase (tyrosine hydroxylase), an enzyme that catalyzes the conversion of tyrosine to dihydroxyphenylalanine, a precursor to dopamine, norepinephrine, and epinephrine. Inhibition of tyrosine hydroxylase can lead to a depletion of dopamine and norepinephrine in the brain.
Tyrosine phosphorylation involves the introduction of a phosphoryl group into a compound through the formation of an ester bond between a tyrosine residue in the compound and a phosphorus moiety.
A member of the Tyrphostin family of tyrosine kinase inhibitors that inhibits epidermal growth factor receptor tyrosine kinase. (NCI)
A protein tyrosine inhibitor that is used as a negative control for the inhibition of epidermal growth factor receptor tyrosine kinase activity. (NCI)
A member of the tyrphostin family of tyrosine kinase inhibitors that inhibits the GTPase activity of transducin and competitively inhibits calcineurin activity. (NCI)
A protein tyrosine kinase inhibitor that blocks tumor necrosis factor alpha induced cytotoxicity. (NCI)
A member of the Tyrphostin family of tyrosine kinase inhibitors that selectively inhibits platelet-derived growth factor beta-receptor kinase and angiogenesis. (NCI)
A member of the Tyrphostin family of tyrosine kinase inhibitors that inhibits platelet derived growth factor (PDGF), autophosphorylation and PDGF-induced mitogenesis in fibroblast. (NCI)
An enantiomer of tyrosine kinase inhibitor that inhibits epidermal growth factor receptor kinase autophosphorylation and phosphorylation of the poly-GAT. (NCI)
A member of the tyrphostin family of tyrosine kinase inhibitors that inhibits epidermal growth factor receptor and blocks metavanadate-induced respiratory burst in alveolar macrophages. (NCI)
Any of a class of synthetic protein tyrosine kinase inhibitors based on the structure of Erbstatin, a compound initially isolated from Streptomyces MH435-hF3 that inhibits the autophosphorylation of the receptor for epidermal growth factor.
The process by which the genetic information of an organism is changed in a stable manner by the radiation in the UV spectrum.
The motor defects of Parkinson's disease are related to the loss of dopaminergic neurons in specific brain regions. Examination of these neurons in diseased tissue has revealed the presence of Lewy bodies, dense aggregates that include the protein alpha-synuclein. A genetic basis for most cases of Parkinson's disease has not yet been identified, but mutations in alpha-synuclein have been associated with at least one rare form of the disease, and mutations in another protein, the parkin gene, are associated with another inherited form of Parkinson's disease. Parkin is found in Lewy bodies along with alpha-synuclein and the parkin protein is an E3 ubiquitin ligase. Parkin appears to work in conjunction with ubiquitin activating (Uba)1, an E1 protein and the ubiquitin-conjugating (Ubc) enzymes UbcH7 and 8. The E1 delivers ubiquitin to the E2 in a cycle that creates an increasing chain of ubiquitin. The Parkin E3 ligates this onto substrates and so tags these proteins in normal cells, targeting them for destruction in the proteasome. One of the proteins that parkin normally targets for destruction is a specific O-glycosylated form of alpha-synuclein. Failure of parkin-mediated degradation of alpha-synuclein may be a key factor leading to the death of dopaminergic neurons. Another substrate of parkin is a GPCR-like protein called Pael-R that accumulates in the ER of affected cells and may cause neuronal cell death. The involvement of Parkin and alpha-synuclein mutations in genetic forms of Parkinson's suggests that failure of ubiquitination and protein degradation may be causative in other forms of Parkinson's. Questions remaining include the cause of the lack of effective ubiquitination in individuals lacking obvious genetic defects in this pathway and how to use this knowledge of ubiquitination and protein degradation in Parkinson's disease to identify therapeutic strategies. (This definition may be outdated - see the DesignNote.)
Protein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to proteins being degraded is performed by a reaction cascade consisting of three enzymes, named E1 (ubiquitin activating enzyme), E2 (ubiquitin conjugating enzyme), and E3 (ubiquitin ligase). Each E3 has specificity to its substrate, or proteins to be targeted by ubiquitination. Many E3s are discovered in eukaryotes and they are classified into four types: HECT type, U-box type, single RING-finger type, and multi-subunit RING-finger type. Multi-subunit RING-finger E3s are exemplified by cullin-Rbx E3s and APC/C. They consist of a RING-finger-containing subunit (RBX1 or RBX2) that functions to bind E2s, a scaffold-like cullin molecule, adaptor proteins, and a target recognizing subunit that binds substrates.
Ubiquitinated Protein Degradation involves the regulated covalent conjugation of one or more ubiquitin residues to one or more sites on a protein that acts as a tag by which the protein-transport machinery ferries the targeted ubiquinated protein to the proteosome for proteolytic destruction.
Ubiquitin is a family of widely distributed proteins found in all eukaryotes that contain a highly conserved sequence of 76 amino acids identical in organisms from humans to insects. It participates in diverse cellular functions by conjugation to other proteins through its carboxy terminus. Ubiquitination is associated with many highly regulated biological events including protein degradation, chromatin remodelling, heat shock, cell cycle progression, differentiation, antigen presentation, retrovirus assembly, apoptosis, signal transduction, transcriptional activation, biological clocks, receptor down regulation, and endocytosis. Protein ubiquitination regulates the half-lives of many proteins by targeting them for degradation. Newly discovered families of ubiquitination and deubiquitination enzymes participate in these processes. Ubiquitination enzymes may provide new therapeutic targets and ways of intervention in many human diseases.
Interchanges of genetic material among different chromosomes following the breaking off of pieces of chromosomes such that the total chromosome composition does not contain all of the genetic material.
Passage or transfer, as of a disease, to a recipient individual due to miscellaneous or not otherwise specified circumstances. (NCI)
A vaccine consisting of lymphoma-specific immunoglobulin that is not conjugated to a carrier molecule. Vaccination with unconjugated lymphoma Ig Id may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against lymphoma cells, resulting in decreased tumor growth. (NCI04)
A vaccine consisting of myeloma-specific immunoglobulin that is not conjugated to a carrier molecule. Vaccination with unconjugated myeloma Ig Id may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against myeloma cells, resulting in decreased tumor growth. (NCI04)
A high grade undifferentiated sarcoma that arises from the endocervix.
A neuroblastoma characterized by the absence of differentiating neuroblasts.
Any adverse event associated with a medical product or procedure that has not been previously observed, whether or not the event was anticipated because of the pharmacologic properties of the study agent or the nature of the medical procedure. This includes events that are more serious than expected or occur more frequently than expected, particularly, any adverse experience, the nature, severity or frequency of which is not consistent with the product label, or with the current investigator brochure for investigational agent; or with the risk information described in the investigational plan or protocol or consent form.
An aziridine alkylating agent that cross-links with DNA, causing inhibition of DNA synthesis. It has been used as a chemosterilant. (NCI)
A benign epithelial neoplasm that produces visible warty projections from the epithelial surface of the ureter.
Papilloma's are benign epithelial neoplasms that produce visible warty projections from epithelial surfaces. Papilloma's of the urethra typically occur just within or on the external meatus. - 2003
An epithelial neoplasm of the urethra, which is morphologically characterized by the presence of a villous architectural pattern.
Bladder tumor associated antigen is a human complement factor H-related protein (hCFHrp), a glycoprotein produced by cancer cells and macrophages but not by normal epithelia. In cell culture, hCFHrp was shown to be produced by several human bladder cancer cell lines, but not by normal epithelial cell lines. By interaction with complement factor C3b, hCFH serves to inhibit the formation of a membrane attack complex, thereby preventing cell lysis. Production of bladder tumor associated antigen may confer a selective growth advantage to cancer cells in vivo by allowing the cells to evade the host immune system. Approved by FDA as a tumor marker for screening test for transitional cell carcinoma.
Agents administered before, with, or after cancer therapy to reduce or prevent damage or toxicity to the urinary tract. (NCI)
An adenomyoma that arises from the uterine corpus and is characterized by the presence of marked glandular architectural complexity. It may recur following excision.
A morphologic variant of leiomyoma arising from the uterine corpus. It is characterized by a dense cellular infiltrate composed of spindle or round cells with scant cytoplasm and a less obvious interlacing fascicle pattern.
A rare morphologic variant of uterine corpus leiomyoma. Macroscopically, it is characterized by large, fungating, and multinodular neoplasm masses arising from the uterine corpus, and extending into the broad ligament or the peritoneal cavity. Microscopically, it shows neoplastic smooth muscle cells infiltrating the myometrium. The neoplastic cells are arranged in a micronodular pattern. Hydropic changes and increased vascularity are also present.
A uterine corpus sarcoma originating from the endometrial stroma. It is further subdivided into low grade and high grade endometrial stromal sarcoma.
A morphologic variant of uterine corpus leiomyoma characterized by the presence of round or polygonal epithelioid smooth muscle cells forming clusters.
A morphologic variant of leiomyosarcoma arising from the uterine corpus. It is characterized by the presence of epithelioid round cells with eosinophilic to clear cytoplasm.
A morphologic variant of uterine corpus leiomyoma characterized by zones of hemorrhagic infarction surrounded by hypercellular areas. It usually develops in women of childbearing years, particularly those that are pregnant, post-partum, or taking oral contraceptives.
A morphologic variant of uterine corpus leiomyoma characterized by significant cytologic atypia. The atypical cells are large with pleomophic hyperchromatic nuclei.
A morphologic variant of uterine corpus leiomyoma characterized by an increased number of mitoses (up to 19 mitoses per 10 high-powered fields).
An unusual condition characterized by the presence of numerous small benign smooth muscle neoplasms located throughout the body of the uterus.
A rare morphologic variant of uterine corpus leiomyoma characterized by the presence of scattered islands of mature adipocytes within the smooth muscle neoplasm.
A rare, indolent, invasive mesenchymal tumor that arises from the endometrial stroma. It is characterized by the presence of a plexiform vasculature, infrequent mitoses, and insignificant cytologic atypia. Late recurrences may occur.
A primary, benign or malignant neoplasm of the uterine corpus characterized by the presence of an epithelial and a mesenchymal component. Representative examples include adenomyoma, adenosarcoma, and carcinosarcoma.
A primary, usually low grade adenocarcinoma of the endometrium in which the majority of the malignant epithelial cells contain abundant intracytoplasmic mucin.
A morphologic variant of uterine corpus leiomyoma characterized by extensive myxoid degeneration of the neoplasm connective tissue stroma.
A morphologic variant of leiomyosarcoma arising from the uterus corpus. It is characterized by the presence of cellular pleomorphism, malignant cells with large nuclei, and a myxoid stroma.
A neoplasm with perivascular epithelioid cell differentiation arising from the uterine corpus wall.
A benign, intermediate, or malignant neoplasm that arises from the uterine corpus and is composed of neoplastic cells with smooth muscle differentiation.
A smooth muscle neoplasm which arises from the uterine corpus and can not be reliably diagnosed as benign or malignant, because of the presence of ambiguous morphologic findings.
A benign or malignant mesenchymal neoplasm of the uterine corpus. Representative examples include leiomyoma, leiomyosarcoma, and endometrial stromal sarcoma.
A rare adenocarcinoma that arises from the uterine ligament.
A clear cell adenocarcinoma of the uterine ligament composed mainly of clear or hobnob cells. The clear cells are large, bizarre, and multinucleated.
A rare endometrioid adenocarcinoma that arises from the uterine ligament. Some of the reported cases were associated with endometriosis.
A rare mucinous adenocarcinoma that arises from the uterine ligament.
A benign, borderline, or malignant neoplasm that affects the uterine ligaments. Representative examples include Wolffian adnexal tumor, papillary cystadenoma, and adenocarcinoma.
A rare serous adenocarcinoma that arises from the uterine ligament.
A peptide vaccine consisting of amino acids 65 through 76 derived from the tumor suppressor protein Von Hippel-Lindau (VHL) with a glycine substitution at position 74. As a cancer vaccine, VHL-59: 65-76(V74G) may stimulate a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing this VHL mutant protein.
A peptide vaccine consisting of amino acids 116 through 128 derived from the tumor suppressor protein Von Hippel-Lindau (VHL) with a frameshift mutation. As a cancer vaccine, VHL-59: 116-128(FrSh116-128) peptide may stimulate a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing this VHL mutant protein.
A peptide vaccine derived from the von Hippel-Lindau (VHL) tumor suppressor protein, a general transcription factor. VHL14 peptide is a point mutation variant of the VHL protein; the mutation is in amino acid position 166. It might be used to elicit or boost cellular immunity to cancers that expressing the von Hippel-Lindau mutation. (NCI04)
A peptide vaccine derived from the von Hippel-Lindau (VHL) tumor suppressor protein, a general transcription factor. VHL16 peptide, also known as S111I, is a point mutation variant of the VHL tumor suppressor protein; the mutation is in amino acid position 111. Vaccination with this agent may stimulate a cytotoxic T-cell response in patients with VHL-associated cancers that express this variant of the VHL tumor suppressor protein. (NCI04)
A peptide vaccine derived from the von Hippel-Lindau (VHL) tumor suppressor protein, a general transcription factor. VHL2 (Y12M) peptide is a point mutation variant (from tyrosine to methionine at amino acid position 12) of the VHL protein. Vaccination with this peptide may stimulate a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing this VHL mutant protein.
A vaccine component consisting of a protein, small peptide, or polysaccharide, natural or synthetic, that once administered is bound by antibody, thereby inducing mechanisms of antibody-dependent cell-mediated cytotoxicity (ADCC). In cancer immunotherapy, a cancer vaccine containing specific tumor-associated antigens (TAAs) may be used to boost an immune response against a tumor expressing those TAAs. (NCI04)
A class of antineoplastic vaccines containing the vaccinia virus, originally used for immunization against smallpox, as a viral vector and immunogenic substance.
Vacuolar Protein Sorting consists of subcellular and biochemical mechanisms involving cell membranes that govern the subcellular location of certain membrane-bound or -associated proteins.
A carcinoma that arises from the vagina and is characterized by the presence of nests of basaloid cells with focal glandular formations.
An adenoid cystic carcinoma that arises from the vagina. Myoepithelial cells are usually not present.
A glandular epithelial neoplasm that arises from the vagina and shows intestinal differentiation.
A malignant mixed epithelial and mesenchymal neoplasm that arises from the vagina and is characterized by the presence of a malignant mesenchymal component and a benign or atypical mullerian-type epithelial component.
A carcinoma that arises from the vagina and is characterized by the presence of malignant glandular and malignant squamous epithelial components.
A squamous cell carcinoma that arises from the vagina and is characterized by the presence of nests of malignant basaloid squamous cells with scant amounts of cytoplasm.
A neoplasm that arises from the vagina and is characterized by the proliferation of subepithelial benign dendritic melanocytes.
An aggressive mixed epithelial and mesenchymal neoplasm that arises from the vagina and is characterized by the presence of a malignant epithelial component and a malignant mesenchymal component.
A locally infiltrating, non-metastasizing vaginal angiomyxoma. It may recur following resection.
A rare adenocarcinoma that arises from the vagina with histologic features resembling the endometrioid adenocarcinoma of the endometrium.
A benign or malignant neoplasm that arises from the vagina and is characterized by the presence of neoplastic glandular epithelial cells. Representative examples include adenoma, endometrioid adenocarcinoma, and clear cell adenocarcinoma.
A squamous cell carcinoma that arises from the vagina and is characterized by the presence of keratin pearls. Intercellular bridges and cytoplasmic keratinization are usually present.
A rare adenocarcinoma that arises from the vagina and is characterized by the presence of tubular structures lined by atypical epithelial cells that resemble remnants of mesonephric duct.
A benign or malignant neoplasm that arises from the vagina and is characterized by the presence of epithelial and mesenchymal elements. This category includes benign mixed tumor, adenosarcoma, carcinosarcoma, and malignant mixed tumor resembling synovial sarcoma.
A rare adenocarcinoma that arises from the vagina with histologic features resembling cervical mucinous adenocarcinoma, endocervical type or cervical mucinous adenocarcinoma, intestinal variant.
A benign papilloma that arises from the vagina in infants and young women.
A squamous cell carcinoma that arises from the vagina and is characterized by the presence of polygonal squamous cells. Intercellular bridges and cytoplasmic keratinization may be present, but keratin pearls are absent.
A rare neuroendocrine carcinoma that arises from the vagina and is composed of small cells.
A benign or malignant mesenchymal neoplasm of the vagina. Representative examples include leiomyoma, rhabdomyoma, leiomyosarcoma, endometrioid stromal sarcoma, and botryoid-type embryonal rhabdomyosarcoma.
A benign or malignant neoplasm that arises from the squamous epithelium of the vagina. Representative examples include condyloma acuminatum, squamous papilloma, and squamous cell carcinoma.
An adenoma that arises from the vagina and is characterized by a tubular architectural pattern.
An adenoma that arises from the vagina and is characterized by a tubulovillous architectural pattern.
A carcinoma that arises from the vagina and is characterized by the lack of specific cellular differentiation.
A high grade infiltrating sarcoma that arises from the vagina. It is characterized by the presence of malignant small spindle cells with scant cytoplasm.
An adenoma that arises from the vagina and is characterized by a villous architectural pattern.
A squamous cell carcinoma that arises from the vagina and is characterized by a papillary growth pattern, hyperkeratosis, and koilocytosis.
A class of plant alkaloids which include the capsaicins
A benign neoplastic process characterized by the presence of multiple vestibular papillomas in the vulva.
A liposomal formulation of Vincristine designed to reduce toxicity and improve efficacy. Vincristine binds irreversibly to microtubules and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle, thereby arresting tumor cells in metaphase. This agent also depolymerizes microtubules and may also interfere with amino acid, cyclic AMP, and glutathione metabolism; calmodulin-dependent Ca++ -transport ATPase activity; cellular respiration; and nucleic acid and lipid biosynthesis. (NCI)
A change in the rate of division or growth of cells that have undergone cellular transformation, which is usually induced either by infection with or genomic integration of a transforming virus.
A disease state resulting from virus infection.
A viral gene transduction agent used to transfer genes or genetic materials, such as retroviruses and adenoviruses.
A function, activity, or process involving the physical interaction between a virus or viral particle and a cell membrane.
Virus-Induced Membrane Fusion involves merging of an envelope type virus particle with a cellular lipid bilayer membrane, often occurring in the course of viral cell infection.
A finding indicating a deficiency or excess in absorption or assimilation of one or more vitamins.
A human monoclonal antibody that targets the cytokeratin tumor-associated antigen and is used for the detection of recurrence and/or metastases of carcinoma of the colon or rectum. (NCI)
A nevus that arises from the vulva during childhood and grows with increasing age.
An alveolar soft part sarcoma arising from the vulva.
A deep or superficial angiomyxoma of the vulva. It may recur following resection.
A small, well circumscribed melanocytic neoplasm that arises from the vulva and affects women in their reproductive years. It is characterized by the presence of junctional nests of melanocytes. Some of the superficial melanocytes show atypia. During pregnancy the atypical melanocytic changes may appear more prominent. This neoplasm is not associated with the presence of dysplastic nevi in other anatomic areas.
A nevus that arises from the vulva and is characterized by the presence of heavily pigmented dendritic melanocytes exclusively in the dermis.
A benign neoplasm arising from the fibrous tissue of the vulva. It is characterized by the presence of spindle-shaped fibroblasts, numerous dilated vascular channels, and increased cellularity.
A vulvar sweat gland carcinoma characterized by the presence of clear cells.
A nevus that arises from the vulva and is present at birth.
A locally infiltrating, non-metastasizing vulvar angiomyxoma. It may recur following resection.
A rare, elevated and pigmented, compound or junctional nevus that arises from the vulva. It affects women in their reproductive years and may be associated with the presence of dysplastic nevi in other anatomic areas. It is characterized by the presence of epithelioid or spindle-shaped melanocytes exhibiting nuclear pleomorphism and prominent nucleoli.
An eccrine porocarcinoma that arises from the sweat glands in the vulva.
A benign or malignant neoplasm that arises from the vulva and is composed of glandular epithelial cells. Representative examples include adenoma of the minor vestibular glands, Bartholin gland adenoma, and Bartholin gland adenocarcinoma.
A usually benign granular cell tumor that arises from the vulva.
Seborrheic keratosis that arises from follicular structures in the vulva. It is characterized by the presence of prominent squamous eddies.
A rapidly growing squamous cell carcinoma that arises from the vulva. It is self-limited and is characterized by the presence of a central crater that contains squamous cells. The proliferating squamous cells infiltrate the dermis below and produce keratin masses that are pushed towards the surface of the tumor.
A benign smooth muscle neoplasm arising from the vulva. It is characterized by the presence of spindle cells with cigar-shaped nuclei, interlacing fascicles, and a whorled pattern.
A neoplasm that originates from melanocytes and arises from the vulva. This category includes congenital and acquired melanocytic nevus, blue nevus, dysplastic melanocytic nevus, atypical melanocytic nevus, genital type, and melanoma.
A benign neoplasm that arises from sweat glands in the vulva and is characterized by the presence of lobules composed of epithelial cells with clear cytoplasm.
A squamous cell carcinoma that arises from the vulva and is characterized by the absence of keratin pearls.
An epithelioid sarcoma of the proximal type involving the vulva.
A carcinoma that arises from the vulva. It is characterized by the presence of malignant basaloid glandular epithelial cells that resemble sebaceous epithelium and are arranged in cords and nests.
A benign or malignant mesenchymal neoplasm of the vulva. Representative examples include leiomyoma, cellular angiofibroma, angiomyxoma, leiomyosarcoma, liposarcoma, and childhood botryoid-type embryonal rhabdomyosarcoma.
An aggressive squamous cell carcinoma that arises from the vulva and is characterized by the prominence of malignant giant cells.
A benign, precancerous, or malignant neoplasm that arises from the squamous epithelium of the vulva. Representative examples include vestibular papilloma, intraepithelial neoplasia, and squamous cell carcinoma.
A vulvar angiomyxoma arising from the dermis or subcutaneous tissues. It may recur following resection.
A benign neoplasm that arises from eccrine ducts in the vulva and is characterized by the presence of tubules and cysts which are lined by epithelial cells in the densely fibrotic dermis.
A benign neoplasm that arises from the vulva and is characterized by the presence of nests of monomorphic basaloid cells forming small cysts that contain keratin.
A benign or malignant neoplasm that arises from the vulva and is characterized by differentiating characteristics towards sweat or sebaceous glands or hair follicles. Representative examples include trichoepithelioma, syringoma, and eccrine adenocarcinoma.
A squamous cell carcinoma that arises from the vulva and is characterized by the presence of a warty surface and cellular changes that are caused by human papillomavirus infection.
A complex signaling pathway whose name is derived from the DROSOPHILA Wg gene, and the vertebrate INT gene. The signaling pathway is initiated by the binding of WNT PROTEINS to cell surface WNT RECEPTORS which interact with the AXIN SIGNALING COMPLEX and an array of second messengers that influence the actions of BETA CATENIN.
An anti-CD7 immunotoxin comprised of the monoclonal antibody WT1 and the ricin-a chain toxin, causing decreased T-lymphocyte production, natural killer cell activity, and protein synthesis.
This effect refers to the high cellular levels of lactic acid in tumor cells, and is named after Otto Warburg who worked on photosynthesis. Tumor cells use excessive glucose in their rapid growth, and lactic acid is a product of the glycolytic pathway. This process is not inhibited by oxygen, therefore, it is also called aerobic glycolysis.
An ovarian steroid cell tumor not otherwise specified, and characterized by the absence of nuclear atypia, mitotic figures, necrosis, and hemorrhage.
White Petrolatum/Minerals is a compounded agent containing various minerals and white petrolatum, a colloid of semisolid hydrocarbons from petroleum. Approved as a skin protectant, it has topical therapeutic applications since it prevents moisture loss and forms a protective barrier on the skin. White Petrolatum provides an optimal vehicle for delivering many therapeutic ingredients. It is also used in food, plastic and other industries. (NCI04)
A vaccine composed of suspensions of intact cells. In cancer vaccines, whole cell vaccines may refer to vaccines generated from whole cancer cells or cells of the immune system intended to be used in defending against cancers or in promoting tissue regeneration. Traditionally, a whole cell vaccine refers to vaccine made up of inactivated bacteria in contrast to acellular vaccine.
Wild Type and Mutant MGMT Vectors are genetic carrier vehicles containing an in vivo selection marker derived from natural or mutant O-6 methylguanine-DNA methyltransferase (MGMT) and are used in gene therapy and biomedical research for selection of specific traits in targeted cells, such as genes that confer resistance to chemotherapeutic agents. Mutant MGMTs resistant to the MGMT inactivator O-6-benzylguanine (BG) are potent markers for in vivo selection in irradiated and non-myelo ablated mouse models using BG plus alkylating agents to drive selection. (NCI04)
Wnt glycoproteins play a role in diverse processes during embryonic patterning in metazoa through interaction with frizzled-type seven-transmembrane-domain receptors (Frz) to stabilize b-catenin. LDL-receptor-related protein 6 (LRP6), a Wnt co-receptor, is required for this interaction. Dikkopf (dkk) proteins are both positive and negative modulators of this signaling. (This definition may be outdated - see the DesignNote.)
A benign or malignant epithelial neoplasm of probable Wolffian origin. It predominantly arises from the broad ligament and presents as a unilateral adnexal mass.
A radioimmunoconjugate of monoclonal antibody against human carcinoembryonic antigen (CEA), labeled with yttrium 90 (Y-90). CEA is over-expressed in many tumor cell types. Using anti-CEA monoclonal antibody to deliver beta emitting nuclide Y-90 to CEA-positive cells results in tissue specific cytotoxicity.
A murine monoclonal antibody directed against the CD5 antigen and labeled with Yttrium-90, a beta-emitting radioisotope. CD5 is a type-I transmembrane glycoprotein found on thymocytes, T-cells and a subset of B-cells. Yttrium 90 monoclonal antibody T101 may bind to and selectively irradiate and kill CD5-positive tumor cells. Yttrium 90 has a half-life of 2.5 days and can be administered on an outpatient basis. (NCI04)
A humanized BrE-3 monoclonal antibody (MoAb) conjugated with either Yttrium Y90 or Indium 111. MoAb BrE-3 is an IgG1-kappa murine monoclonal antibody, which recognizes breast epithelial mucin, a surface antigen expressed by breast cancer cells. This human/mouse chimeric antibody (by joining the murine variable domains to human constant domains) has the same binding affinity and is considerably less immunogenic to humans than the original murine antibody. This MoAb has both imaging and therapeutic uses, when conjugated with either Yttrium Y90 or Indium 111, which emits beta particles and causes cytotoxicity to breast cancer cells.
A fragment of fibroblast growth factor-5 (FGF-5). Originally isolated from a renal cell carcinoma cell line that overexpressed FGF-5, FGF-5:117-126 peptide is recognized by tumor infiltrating cytotoxic T lymphocytes. Overexpressed by several cancer cell types, this peptide is being tested as a potential target for antineoplastic immunotherapies. (NCI04)
A monoclonal anti-idiotype antibody adsorbed to aluminum hydroxide gel (AluGel) with potential antineoplastic activity. 11D10 AluGel anti-idiotype monoclonal antibody mimics the human milk fat globule (HMFG) antigen found in breast and other cancers. Vaccination with 11D10 AluGel anti-idiotype monoclonal antibody may induce a host antibody response against tumor cells positive for the HMFG antigen. (NCI04)
A radiopharmaceutical comprised of a thymidine analog, 5-iodo-2''-deoxyuridine (idoxuridine), labelled with the Auger electron emitter Iodine 125 that has been used as an assay for testing cell-mediated cytotoxicity and exhibits cytotoxicity by incorporating into DNA, causing DNA strand breaks. (NCI04)
A recombinant 19-residue peptide vaccine consisting of amino acids 161 through 180 of the cancer/testis (CT) antigen. ESO-1 (161-180) peptide vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for ESO-1, resulting in decreased tumor growth. ESO-1 is expressed in a variety of cancers, including melanoma, breast, bladder, prostate, and hepatocellular cancers. (NCI04)
A conjugate of a murine immunoglobulin antibody directed against the Lewis carbohydrate epitope (B3 antigen) and a isothiocyanatobenzyl derivative (1B4M) of diethylenetriaminepentaacetic acid (DTPA) with potential use in cancer immunotherapy. The Lewis carbohydrate epitope is present on a variety of proteins located on the surface of many different types of tumor cells and a limited number of normal tissues. (NCI04)
A ureido-derivative of pyrimidine developed to induce leukemic cell differentiation. This agent has been shown to induce erythroleukemia cell differentiation. (NCI04)
A podophyllic acid derivative of podophyllotoxin, a substance extracted from the mandrake root Podophyllum peltatum. Possessing potent antineoplastic properties, 2-ethylhydrazide binds to and inhibits topoisomerase II and its function in ligating cleaved DNA molecules, resulting in the accumulation of single- or double-strand DNA breaks, the inhibition of DNA replication and transcription, and apoptotic cell death.
A hydroxysteroid dehydrogenase inhibitor that is specific for 3-hydroxysteroid dehydrogenase.
An aluminum hydroxide-precipitated recombinant monoclonal antibody in which the heavy and light chain variable domains mimic a specific epitope of the tumor-associated protein carcinoembryonic antigen (CEA). This agent may be used as a cancer vaccine against tumors that express CEA. (NCI04)
A ureido-derivative of pyrimidine developed to induce leukemic cell differentiation. This agent ahs been shown to induce erythroleukemia cell differentiation. (NCI04)
A thiosemicarbazone antimetabolite. A derivative of 5-hydroxypicolinaldehyde, 5-HP inhibits DNA polymerase, resulting in the inhibition of DNA replication and cell death. (NCI04)
An ureido-derivative of pyrimidine and a potent inducer of neoplastic cell differentiation. (NCI04)
A cytogenetic abnormality that refers to deletion of part of the long arm of chromosome 5. It is associated with the development of myelodysplastic syndrome with isolated deletion (5q), acute myeloid leukemia with multilineage dysplasia, and acute myeloid leukemia with myelodysplasia-related changes.
An ureido-derivative of pyridine and a potent inducer of neoplastic cell differentiation. (NCI04)
A finding indicating that there is a decrease in the size and the extent of tissue involvement by a malignant tumor in a patient.
The covalent chemical or post-translational biochemical addition of an acetyl group(s) to a peptide or protein. (NCI)
An analogue of the anthracycline antineoplastic antibiotic doxorubicin. 13-Deoxydoxorubicin intercalates DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. This agent was designed to be a non-cardiotoxic anthracycline antibiotic.
A fluorinated derivative of the 2-nitroimidazole etanidazole. EF5 is effective in accessing oxygen levels in tumor tissue through its adduct formation to intracellular macromolecules in the absence of oxygen. Reduction of this agent is carried out by a diverse group of enzymes in the cytoplasm, microsomes and mitochondria. Tissue hypoxia detection via EF5 has been reported in several cancers, including squamous cell carcinoma of the cervix and the head and neck, and in sarcoma.
Antiquated term describing follicular (nodular) or diffuse non-Hodgkin lymphomas that are composed of a mixture of large cells: large cleaved cells, with irregular nuclei without visible nucleoli; and large non-cleaved cells (centroblasts), having a rounder nucleus with two to three small, peripherally placed nucleoli and a small amount of basophilic cytoplasm. The follicular variants represent mature B-cell lymphomas, whereas the diffuse variants can be either mature B- or mature T-cell lymphomas. --2004
Allowing establishment of infection or acceptance of graft material.
A murine IgG1 monoclonal antibody directed against Lewis Y antigen and related carbohydrate antigens of cell surface glycoproteins found in many tumor cells. Monoclonal antibody B3 can be conjugated with various toxins in order to target their cytotoxic activity to tumor cells expressing these carbohydrate antigens. (NCI04)
Nodular sclerosis Hodgkin lymphoma in which at least 75% of the tumor nodules contain scattered Reed-Sternberg cells. The background cellular infiltrate is lymphocytic, mixed, or fibrohistiocytic.
Intraurothelial neoplasia characterized by dysplastic changes which are not severe enough to warrant the diagnosis of bladder carcinoma in situ. -- 2003
Bone density and structure is maintained through a balance of bone resorption by osteoclasts and bone deposition by osteoblasts. The combination of simultaneous resorption and deposition creates continual remodeling of bone while excess osteoclast activity leads to an imbalance and a loss of bone density, causing osteoporosis. RANK (receptor activator of NF-kB ligand) is a receptor in the TNF receptor gene family that is involved in osteoclast differentiation. RANK-ligand, also called osteoprotegerin-ligand, binds to RANK, induces receptor dimerization, and activates downstream signaling. Osteoprotegerin is a decoy receptor for RANK-ligand that suppresses osteoclast activity and bone remodeling, helping to maintain balanced bone remodeling. RANK-ligand and osteoprotegerin are produced by osteoblasts and some factors regulate osteoclast activity indirectly through their action on the expression of these factors by osteoblasts. Binding of RANK-ligand to RANK activates signaling through TRAF-6. TRAF-6 induces several downstream signaling events, including activation of NF-kB, c-Fos and the kinase JNK1. Jnk-1 activation contributes to fos activation by RANK-ligand and may be involved in the modulation of RANK-ligand by other factors such as estrogen. Mice lacking the c-Fos gene have overly dense bone and decreased bone resorption due to reduced osteoclast differentiation, indicating that c-Fos is an important mediator of osteoclast differentiation. One of the results of c-Fos induction is transcriptional activation of interferon-beta. Interferon-beta binds to its receptor on neighboring osteoclast precursor cells to block RANK-ligand signaling and down-regulate c-Fos expression, inhibiting further osteoclast differentiation. Mice lacking interferon-beta or the interferon-beta receptor lose bone due to uncontrolled osteoclast activity, demonstrating the importance of this mechanism in vivo. Interferon-beta signaling could be used as a mechanism to prevent osteoporosis and other conditions involving excessive osteoclast resorption of bone. (This definition may be outdated - see the DesignNote.)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous macrophage inflammatory protein-1, a member of the CC chemokine family produced by activated macrophages. Macrophage inflammatory protein-1 alpha activates granulocytes and induces pro-inflammatory cytokine synthesis. The addition of macrophage inflammatory protein-1 alpha to a vaccine consisting of a DNA immunogen or a pro-inflammatory peptide may enhance vaccine-induced host immune anti-tumor responses. (NCI04)
A molecular genetic abnormality indicating the presence of multiple copies of the MYCN gene.
Ischemic tissue necrosis characterized by the preservation of the architectural pattern and a necrotic ghost appearance of the cells.
The isethionate salt of piritrexim, a synthetic antifolate agent with antiparasitic, antipsoriatic and antitumor properties. Piritrexim inhibits the enzyme dihydrofolate reductase enzyme, thereby disrupting folate metabolism and DNA synthesis and cell division.
A recombinant polypeptide chemically identical to or similar to the endogenous cytokine transforming growth factor-beta-2 (TGF-beta-2). TGF-beta-2 modulates cell growth and immune function and may promote or inhibit tumor growth, depending on the tumor cell type. TGF-beta-2 may also suppress host immune system recognition of and/or response to tumor cells.
A peptide based vaccine consisting of amino acids 12 through 20 of the E7 gene of the Human Papilloma Virus type 16. HPV-16 E7 12-20 peptide vaccine may elicit a specific CD8 T-cell response to the E7 oncogene protein, thereby inhibiting the abrogation of p53 and pRb function and thus prevent tumorigenesis. (NCI04)
A laboratory test result indicating an increased amount of cholesterol in the blood.
Higher than normal levels of sodium in the circulating blood.
An abnormal increase in the level of triglycerides in the blood.
Dimeric growth factors of the TGF family with effects on a range of cell types in addition to promoting FSH release in gonadal sites. Composed of two of the subunits of inhibin, the isoforms A and B.
A therapeutic analogue of the endogenous CXC cytokine macrophage inflammatory protein-2 alpha. Macrophage inflammatory protein-2 alpha attracts and activates neutrophils and may play a role in cell proliferation. In experimental models of acute hepatic injury, macrophage inflammatory protein-2 alpha has been shown to promote liver regeneration by stimulating the proliferation of hepatocytes. (NCI04)
The hydrochloride salt form of piroxantrone, an anthrapyrazole antineoplastic antibiotic. Piroxantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Although less cardiotoxic than doxorubicin, this agent exhibits a narrow spectrum of antineoplastic activity.
A recombinant chemokine of human lymphotactin which is produced by activated progenitor T cells and characterized by specific chemotactic activity for lymphocytes. (NCI)
A binding interaction that results in localization of the ligand.
Thyroid gland carcinoma that arises from parafollicular cells (C cells) and occurs in a mouse.
A spectrum of disorders characterized by clonal expansions of the peripheral blood LYMPHOCYTE populations known as large granular lymphocytes which contain abundant cytoplasm and azurophilic granules. Subtypes develop from either CD3-negative NATURAL KILLER CELLS or CD3-positive T-CELLS. The clinical course of both subtypes can vary from spontaneous regression to progressive, malignant disease.
A class of formulated therapeutic analogs of the endogenous gonadotropin that stimulates or promotes the function of the gonads. Therapeutic gonadotropins are derived from animal or recombinant sources. Gonadotropins include follicle-stimulating hormone, luteinizing hormone and chorionic gonadotropin. These agents stimulate discrete cellular components of the gonads, exerting effects in both males and females. (NCI04)
Any recombinant analog of endogenous interleukin-2 (IL-2), a cytokine involved in intercellular communication related to cell differentiation, proliferation, inflammation, hematopoiesis, neuronal functions, and release of hormones. IL-2 binds to and activates specific receptors, triggering expression of specific genes, and may induce T cell-mediated tumor regression in some tumor types.
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-1 (IL-1). Produced mainly by monocytes, endogenous IL-1 plays a role in hematopoiesis, is a potent stimulator of T-cell activity, may promote or inhibit tumor growth, depending on tumor type. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous protein cytokine interleukin 1 (IL-1)-beta. Produced by monocytes and activated macrophages, endogenous mature IL-1 is generated through proteolytic cleavage by proteases such as IL-1-beta converting enzyme (ICE). This agent promotes angiogenesis, fibroblast proliferation, and neutrophil chemotaxis; it also regulates the functions of lymphocytes and epithelial cells and is involved in the 'acute phase response' to infection. (NCI04)
A recombinantly produced form of human nerve growth factor (NGF) protein with potential therapeutic application. Endogenous NGF can regulate neuronal proliferation, differentiation and survival.
Recombinant form of endogenous neurotrophic factors, a family of polypeptide growth factors produced by peripheral target tissues as well as the nervous system. Neurotrophic factors are critical to neuronal growth, regeneration, survival, and differentiation. (NCI)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous fibroblast growth factor 1 (FGF-1. Because of the mitogenic and angiogenetic effects of FGF-1 on fibroblasts and endothelial cells, therapeutic FGF-1 has a potential role in wound healing; because FGF-1 has been shown to induce neurogenesis, therapeutic FGF-1 may have a role in nerve regeneration. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine Flt3. Flt3 ligand binds to the Flt3 tyrosine kinase receptor and, synergistically with other growth factors, stimulates the proliferation and mobilization of bone marrow precursor cells, including CD34+ cells, and dendritic cells. When proteolytically cleaved, the transmembrane isoform of Flt3 ligand generates the soluble form soluble Flt3 ligand, which is also biologically active.
A heat-inactivated preparation of Corynebacterium parvum with immunoadjuvant properties. Therapeutic Corynebacterium parvum may stimulate host antitumor immune responses when added to cancer vaccines. (NCI04)
A recombinant human soluble protein corresponding to amino acids 114-281 of the Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (RhApo2L/TRAIL) with potential antineoplastic activity. Dulanermin binds to and activates TRAIL receptors 1 and 2 (TRAIL-R1/R2), which may activate caspases and induce p53-independent apoptosis in TRAIL-R1/R2-expressing tumor cells. The pro-apoptotic cell surface receptors TRAIL-R1 and -R2, also known as DR4 (death receptor 4) and DR5 (death receptor 5), are members of the TNF receptor family and are overexpressed by a variety of cancer cell types.
A recombinant therapeutic agent which is chemically identical to or similar to endogenous fibroblast growth factor 2 (FGF-2). Reflecting its endogenous role, therapeutic FGF-2 exhibits a wide spectrum of biological activities, including the promotion of growth and differentiation in target cells, the regulation of hormone secretion, and the promotion of angiogenesis. This agent's mitogenic effects on fibroblasts and endothelial cells indicates a potential role in therapeutic angiogenesis and wound healing. In addition, therapeutic FGF-2 may stimulate neurogenesis and protect neurons against degeneration; FGF-2 supplementation via gene transfer may reduce neuronal degeneration in experimental animal models. (NCI04)
A pro-inflammatory delta chemokine with potential antineoplastic activity. Fractalkine induces the adhesion and migration of T lymphocytes, monocytes and natural killer (NK) cells. In lymphomas, this agent may promote cell-mediated lympholysis by recruiting activated NK cells. (NCI04)
The dicitrate salt of a synthetic pipecolinate derivative with potential chemosensitizing activity. Biricodar binds directly to the plasma membrane drug-efflux pumps P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP-1) and inhibits their activities, which may result in increased intracellular accumulation and retention of cytotoxic agents.
One of a group of recombinant therapeutic glycoprotein cytokines with antiviral, anti-proliferative, and immunomodulating activities. Interferons bind to specific cell-surface receptors, leading to the transcription and translation of genes with interferon-specific response elements (ISREs). The resultant proteins mediate many complex effects, ultimately leading to inhibition of viral protein synthesis and cellular growth, alteration of cellular differentiation, interference with oncogene expression, activation of natural killer cells, alteration of cell surface antigen expression, and augmentation of lymphocyte and macrophage cytotoxicity. The production of endogenous interferons is induced in response to foreign agents such as bacteria, viruses and parasites and to tumor cells.
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-9 (IL-9). Produced by CD4+ lymphocytes, IL-9 stimulates the proliferation of T-helper cells and the growth of mast cells and megakaryoblasts. This agent also enhances the growth of some leukemia cell lines and may play a role in the pathogenesis of Hodgkin disease and large cell anaplastic lymphoma. (NCI04)
The recombinant analogue of an endogenous cytokine interleukin 13 with potential antineoplastic activity. Produced by lymphocytes and exhibiting a variety of functions, interleukin-13 (therapeutic) inhibits DNA synthesis and regulates inflammatory and immune responses. In animal models, this agent has been shown to kill tumor cells both directly and indirectly by activating the host immune system at the tumor site. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous human monocyte chemoattractant protein-1, a member of the CC chemokine family which is chemotactic for monocytes. (NCI04)
A recombinant human antiapoptotic growth factor. Recombinant insulin-like growth factor (IGF) binds to and activates the insulin and IGF receptors; activation of these receptors initiates intracellular phosphorylation events and the activation of several signaling pathways, thereby promoting cellular proliferation and inhibiting apoptosis. High levels of circulating endogenous insulin-like growth factor may indicate a poor prognosis in some cancers. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous vascular endothelial growth factor (VEGF). Produced by a wide variety of cell types, endogenous VEGF is a homodimeric, glycosylated protein that is a highly specific mitogen for vascular endothelial cells; significantly influences vascular permeability; appears to play a role in neovascularisation under physiological conditions; is a potent chemoattractant; has pro-coagulatory activities; and is hypoxia-inducible. Therapeutic VEGF may be used to induce angiogenesis in the treatment of ischemic conditions and may have a role in stimulating nerve regeneration. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine tumor necrosis factor-alpha with antineoplastic properties. Tumor necrosis factor-alpha binds to and activates ""death receptors"" on the cell surface, resulting in apoptosis and cell death by the p53-independent extrinsic pathway. This agent also disrupts tumor vascularization. (NCI04)
A liposome-encapsulated preparation of the hydrochloride salt of the anthracycline antineoplastic antibiotic doxorubicin. Doxorubicin intercalates between DNA base pairs, thereby hinders the movement of replication machinery along DNA strands, as well as blocks the activity of topoisomerase II during replication. As a result, this agent causes DNA adducts formation, renders single- and double-stranded DNA breakages that induce DNA repair and or apoptotic processes. Doxorubicin also generates reactive oxygen species that leads to cytotoxicity secondary to lipid peroxidation of cell membrane lipids. Liposomal delivery of doxorubicin HCl improves drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic drug effects. A liposomal formulation of doxorubicin also modulates toxicity, specifically the cardiac effects commonly seen with anthracycline antitumor drugs.
A recombinant agent, chemically identical or similar to the endogenous small inducible cytokine B10 (IP-10). Interferon-alpha inducible protein 10 is secreted from macrophages, endothelial cells, and keratinocytes in response to stimulation of IFN-gamma. This agent is a potent inhibitor of angiogenesis, bone marrow colony formation, and is a chemoattractant for monocytes and T-cells, promotes T-cell adhesion to endothelial cells, and probably participates in chronic cell-mediated inflammatory reactions.
Connective Tissue-Activating Peptide III is a platelet-derived growth factor that stimulates in fibroblasts mitogenesis, extracellular matrix synthesis, glucose metabolism, and plasminogen activator synthesis through interaction with a GPCR. It is present in platelet granules, released by inducers of platelet aggregation, and is chemoattractant for fibroblasts, presumably for repair. Pro-platelet basic protein is the precursor of platelet basic protein (PBP) and CTAP III. Upon platelet activation they are released and processed in plasma to beta-thromboglobulin and neutrophil-activating peptide-2. The thrombocidins TC1 and TC2 are variants of NAP2 and CTAP III, respectively. TC1 and TC2 differ from NAP2 and CTAP III by their bactericidal and fungicidal properties, which apparently do not involve pore formation. (from OMIM 121010 and NCI)
A therapeutic recombinant analogue of a member of the endogenous CC chemokines with potential antineoplastic activity. Expressed by various lymphoid tissues, endogenous 6Ckine is chemotactic for B and T lymphocytes and dendritic cells.
A recombinant agent which is chemically identical to or similar to the endogenous protein cytokine interleukin-1 (IL-1). The IL-1 precursor is produced by monocytes, activated macrophages, and other cell types; mature IL-1 is generated by proteolytic cleavage by proteases such as IL-1-beta converting enzyme (ICE). This agent enhances T cell proliferation and B cell growth and differentiation and induces the expression of proinflammatory cytokines. (NCI04)
A modified version of Vitaxin, a humanized monoclonal IgG1 antibody to alpha(v)beta(3)integrin. Exhibiting improved affinity to alpha(v)beta(3)integrin compared to first-generation Vitaxin, Vitaxin-2 blocks the binding of ligands, such as vitronectin, to alpha(v)beta(3) integrin, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis. (NCI04)
TRIad of COstimulatory Molecules (B7-1, ICAM-1 and LFA-3). An immunostimulant.
The sodium salt form of batabulin, a synthetic pentafluorophenylsulfonamide with potential antineoplastic activity. Batabulin covalently binds to and selectively modifies the beta 1, beta 2, beta 3, and beta 4 isotypes of beta tubulin at a conserved cysteine residue, resulting in disruption of microtubule polymerization, collapse of the cytoskeleton, an increase in chromosomal ploidy, cell cycle arrest, and tumor cell apoptosis.
A recombinant peptide hormone chemically identical to or similar to human polypeptide hormone corticotropin (adrenocorticotropic hormone; ACTH). Secreted by the anterior pituitary gland, circulating ACTH stimulates the adrenal cortex to secrete adrenocortical steroids, especially cortisone, which elevate blood pressure in response to stress. With normally functioning adrenal glands, recombinant corticotropin could be used to achieve pharmacologic effects similar to those from cortisone administration.
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous glycoprotein cytokine hepatocyte growth factor (HGF), which is produced by the liver and the pancreas. Endogenous HGF synthesis is stimulated by injuries affecting liver tissues. This agent, a potent angiogenic and neurotrophic factor and a multifunctional cytokine that acts as a mitogen, motogen and a morphogen, is important for organogenesis and tissue regeneration. Therapeutic HGF has been shown to attenuate brain ischemic injury in animal models through angiogenic and neuroprotective actions. (NCI04)
Studies which look at the causal relationship between depression and suicide.
A breast hamartoma characterized by the presence of adipose tissue that contains entrapped glands.
A synthetic microsphere formulation with arterial occlusive properties. Amilomer, a product produced by partially hydrolyzing starch and epichlorohydrin, contains degradable starch microspheres (DSM) with a diameter size of 45 micrometers that are readily degraded by amylase. When used in transcatheter arterial chemoembolization (TACE) procedures, infusion leads to lodging of the microspheres in the precapillary vessels and, consequently, to the occlusion of the hepatic artery. Local occlusion of selected blood vessels in conjunction with intrahepatic chemotherapy administration, results in elevated intracellular hepatocyte drug concentrations and enhances localized cytotoxicity against hepatic tumor lesions.
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous protein cytokine macrophage colony-stimulating factor (M-CSF). Synthesized endogenously by mesenchymal cells, M-CSF stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series and can reverse treatment-related neutropenias. Recombinant M-CSF may also enhance antigen presentation and activate antitumoral cytotoxic T-cells.
A recombinant form of the heparin-binding cytokine pleiotrophin. Developmentally regulated, pleiotrophin functions as a growth factor during embryogenesis and the neonatal period, contributing to trophoblast formation, organ development, bone formation, and early brain development by inducing the differentiation and proliferation of neuronal tissue. Expressed in certain tumor cell types, this agent may stimulate tumor cell growth, angiogenesis, and metastasis. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous fibroblast growth factor 4 (FGF-4). Therapeutic FGF-4 induces vascular permeability, angiogenesis, and arteriogenesis and has potential uses in the treatment of peripheral vascular disease. (NCI04)
Analogues of epothilone B exhibiting antineoplastic activity. Epothilone B analogues bind to tubulin and promote tubulin polymerization and microtubule stabilization, thereby inhibiting mitosis. (NCI)
A therapeutic glycoprotein cytokine chemically identical to or similar to endogenous human stem cell factor with hematopoietic activity. Recombinant human stem cell factor (rhSCF) binds to the receptor tyrosine kinase c-kit, which may stimulate the growth of peripheral blood progenitor cells (PBPCs). This agent works synergistically with other hematopoietic growth factors. rhSCF may promote bone marrow recovery after myeloablative therapies and procedures.
A recombinant therapeutic agent which is chemically identical to or similar to CD40-ligand. CD40-ligand, also known as CD40L/TRAP and CD154, is a type II membrane protein which binds to CD40, a cell surface receptor that belongs to the tumor necrosis factor receptor family; CD40 is expressed on B lymphocytes, monocytes, dendritic cells (DC), hematopoietic progenitors, endothelial cells and epithelial cells. Recombinant CD40-ligand may be used to activate DC ex vivo via CD40 binding; CD40-ligand-activated DC may provide or augment a protective antitumor immunity when administered in dendritic cell cancer vaccines. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to endogenous glial cell line-derived neurotrophic factor (GDNF). GDNF is a glycosylated, disulfide-bonded homodimer distantly related member of the transforming growth factor-beta superfamily. This agent is important in the development and maintenance of dopamine neurons, has restorative effects in a wide variety of rodent and primate models of Parkinson disease, and may have utility in the treatment of Parkinson's disease, which is marked by progressive degeneration of midbrain dopaminergic neurons. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to an endogenous glycoprotein which inhibits pituitary production of follicle-stimulating hormone (FSH). Produced and secreted by the testis or ovarian follicle, endogenous inhibin B contributes to the control of gametogenesis, embryonic and fetal development, and hematopoiesis. (NCI04)
A recombinant agent, which is chemically identical to or similar to the endogenous protein Fas ligand OX40, a member of the tumor necrosis factor (TNF) family. Expressed by antigen presenting cells (APC), OX40 ligand binds to the OX40 receptor on CD4 T-cells, thereby priming antigen-specific activation of CD4 T-cells and inducing CD4 T-cell secretion of interleukin 4 (IL-4). (NCI04)
One of a number of chemotactic cytokines. Alpha chemokines are small polypeptides released by macrophages, endothelial cells, keratinocytes, fibroblasts, and smooth muscle cells in the presence of infection or physical tissue damage. In a therapeutic setting, these agents may act as chemoattractants to recruit neutrophils and T cells from the blood to sites of infection or damage and may either promote or inhibit tumor growth by modulating tumor-associated angiogenesis and metastasis. Also known as CXC chemokines. (NCI04)
An antiangiogenic polysaccharide toxin derived from group B streptococcus.
A recombinant therapeutic agent which is chemically identical to or similar to an endogenous glycoprotein which inhibits pituitary production of follicle-stimulating hormone (FSH). Produced and secreted by the testis or ovarian follicle, endogenous inhibin A contributes to the control of gametogenesis, embryonic and fetal development, and hematopoiesis and enhances LH-stimulated androgen secretion by human thecal cells. (NCI04)
The hydrochloride salt form of cemadotin, a synthetic dolastatin 15 analogue with potential antineoplastic activity. Cemadotin suppresses spindle microtubule dynamics by binding to tubulin, thereby blocking mitosis. (NCI04)
A recombinant form of the endogenous polypeptide hormone that exerts immunomodulatory effects primarily on mononuclear cells. Prothymosin alpha stimulates the production of various cytokines including granulocyte/macrophage colony stimulating factor (GM-CSF) alpha, gamma interferon (IFN) and interleukins such as IL-2. This agent may also increase some tumor antigens expression, thus inducing better T lymphocyte responses to tumor cells. Combined with chemotherapy, prothymosin alpha may exhibit significant anti-tumor effects. This agent also helps to regenerate lymph node and bone marrow cells after treatment with certain toxic chemotherapeutics. (NCI04)
A new generation organic platinum analog with an extended spectrum of antineoplastic activity. Designed to overcome platinum drug resistance, picoplatin alkylates DNA, forming both inter- and intra-strand cross-linkages, resulting in inhibition of DNA replication and transcription, and the induction of apoptosis.
The hydrochloride salt of arzoxifene, a synthetic aromatic derivative with anti-estrogenic properties. Arzoxifene binds to estrogen receptors as a mixed estrogen agonist/antagonist. In comparison to other selective estrogen receptor modulators (SERMs), arzoxifene exhibits greater bioavailability and higher anti-estrogenic potency in the breast than raloxifene; it exhibits reduced estrogenicity in the uterus compared with either tamoxifen or raloxifene. This agent may have beneficial effects on bone and the cardiovascular system.
A semisynthetic, second-generation taxane derivative with potential antineoplastic activity. Ortataxel binds to and stabilizes tubulin molecules, thereby interfering with the dynamics of microtubule assembly/disassembly. This results in the inhibition of cell division and cellular proliferation. As it represents a poor substrate for P-glycoprotein (P-gp), multi-drug resistance protein (MRP-1) and breast cancer resistance protein (BCRP) mediated efflux, ortataxel modulates multi-drug resistance mechanisms and may be useful for treating multi-drug resistant tumors that express Pgp, MRP-1 and BCRP.
The action of enzymes, regulators, chaperones etc.
A recombinant form of thyroglobulin identical to or similar to the endogenous iodine-containing glycoprotein. Thyroglobulin is synthesized in the thyroid follicular cell, and is the precursor of thyroid hormones T3 and T4. Thyroglobulin levels can serve as a tumor marker for monitoring the status of differentiated thyroid carcinomas.
A methylglyoxal-bis(guanylhydrazone) (MGBG) derivative with potential antineoplastic and antiviral properties. Sardomozide selectively binds to and inhibits S-adenosylmethionine decarboxylase (SAMDC), an enzyme essential for the biosynthesis of polyamines, such as spermine and spermidine that bind to DNA and play critical roles in cell division, cell differentiation and membrane function. By inhibiting SAMDC, sardomozide reduces the intracellular polyamine concentration, thereby interfering with cell growth and differentiation. In addition, this agent also exhibits anti-HIV effect via suppressing expression of eukaryotic translation initiation factor 5A (eIF-5A), which is essential for retroviral replication.
A synthetic peptide identical to the endogenous nonapeptide hormone with antidiuretic property. Synthesized in the hypothalamus and stored/released from the posterior lobe of the pituitary, argipressin's primary function is regulating extracellular fluid volume. This agent can also act as a vasoconstrictor, increasing blood pressure and systemic vascular resistance.
A recombinant form of interleukin-3, a cytokine produced by activated T-cells and mast cells involved in intercellular communication, hematopoiesis, and inflammation. IL-3 binds and activates specific receptors on hematopoietic cells and in the nervous system, triggering expression of specific genes via the Ras signaling pathway and through Jak2 activation. This agent stimulates the proliferation of pluripotent hematopoietic progenitor cells.
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-6 (IL-6) with antiapoptotic, proinflammatory, antiinflammatory, proproliferative and proangiogenic activities. IL-6 binds to its receptor (IL-6R), activating a receptor-CD130 receptor complex; the CD130 portion of the complex is a signal transduction protein that activates JAK kinases and Ras-mediated signaling pathways, which in turn activate downstream signaling pathways, resulting in the activation of various transcription factors (STAT, ELK-1, NF-IL-6, etc.) and gene transcription. The physiological effects of IL-6 are complex and varied and include hematopoietic, pyrogenic and thermogenic, proinflammatory, antiinflammatory, proproliferative (anti-apoptotic), and angiogenic effects.
A family of synthetic or recombinant C-type chemokines lacking adjacent cysteine residues and act as chemoattractants for lymphocytes.
A therapeutic chemically synthesized form of the pineal indole melatonin with antioxidant properties. The pineal synthesis and secretion of melatonin, a serotonin-derived neurohormone, is dependent on beta-adrenergic receptor function. Melatonin is involved in numerous biological functions including circadian rhythm, sleep, the stress response, aging, and immunity.
A recombinant peptide that is chemically identical to or similar to the endogenous 70-kD heat shock protein (HSP70). HSP70 is a molecular chaperone that prevents physiologic stress-induced cell death by inhibiting both caspase-dependent and caspase-independent apoptosis. Because this peptide is often overexpressed in tumor cells, autologous vaccination with HSP70 derived from tumor cells may stimulate the host immune system to mount a tumoricidal cytotoxic T lymphocyte (CTL) response. (NCI04)
A recombinant agent, which is chemically identical to or similar to the endogenous cytokine tumor necrosis factor-beta (TNF-beta). Produced predominantly by T-lymphocytes and leukocytes, TNF-beta is cytolytic or cytostatic for many tumor cells, and can inhibit the growth of endothelial cells, resulting in an antiangiogenic effect. (NCI04)
A recombinant therapeutic agent which is chemically identical to or similar to the endogenous glycoprotein hormone human chorionic gonadotropin (HCG). HCG binds to cells of the corpus luteum, thereby stimulating progesterone production and helping to maintain a secretory endometrium. (NCI04)
A class of immunotoxins targeting CD19, a common B-cell marker.
A genetic syndrome which occurs in females. It is caused by the inheritance of only one complete X chromosome (45, X). Clinical signs of the symmetrical form are identical to those of Turner syndrome and include bilateral webbing of the neck and edema of the extremities. Clinical characteristics include decreased stature and under-developed sexual organs. Patients usually have a normal life expectancy.
An immunotherapeutic agent consisting of a plasmid DNA encoding human Interleukin-2 (IL-2) complexed with a cationic lipid, 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl-phosphatidyl-ethanolamine (DMRIE/DOPE), in a 5:1 ratio. Due to the lipophilic nature of this cation liposome complex, this gene transfer system may improve the efficiency of introducing the IL-2 gene into the cells, thereby increasing the production of IL-2 and inducing an immune response.
A drug being studied to make cancer cells less resistant to the effects of chemotherapy.
Formulated therapeutic analogs of one of a number of endogenous cytokine interleukins. Produced by T cells, macrophages, and other cells, interleukins bind to a specific surface receptor on immunohematopoietic cells, thereby inducing a multitude of biologic effects including stimulation of growth, differentiation, and proliferation of lymphocytes and eosinophils; activation of lymphocytes and macrophages; enhancement of mast cell activity; activation of the acute phase response; and stimulation of hematopoiesis. Some interleukins may enhance the host's immune response to malignant cells by stimulating lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL), which are capable of lysing some tumor cells. (NCI04)
A type of cytokine produced by lymphocytes for therapeutic use involving cellular immunity.
A recombinant therapeutic agent which is chemically identical to or similar to an endogenous non-mutated melanocyte differentiation antigen expressed by both normal and malignant melanocytes. Vaccinations with recombinant tyrosinase-related protein-2 may elicit an antitumoral cytotoxic T-cell response against tumor cells and some normal cells that express tyrosinase-related protein-2. (NCI04)
A water-soluble prodrug, consisting of camptothecin covalently linked to polymeric backbone methacryloylglycynamide, with potential antineoplastic activity. After entering tumor cells, the active moiety camptothecin is slowly released from mureletecan via hydrolysis of the ester linkage. Camptothecin, an alkaloid isolated from the Chinese tree Camptotheca acuminata, binds to and stabilizes the topoisomerase I-DNA covalent complex. This inhibits the religation of topoisomerase I-mediated single-stranded DNA breaks and produces potentially lethal double-stranded DNA breaks when encountered by the DNA replication machinery, resulting in the inhibition of DNA replication and apoptosis. Compared to camtpothecin, this prodrug formulation increases camptothecin drug delivery to the tumor site while reducing systemic toxicity.
A bivalent cancer vaccine comprised of a modified vaccinia virus Ankara (MVA) strain encoding human mucin 1 (MUC1) and interleukin-2 (IL-2) with potential immunostimulating and antineoplastic activities. Originally developed for the eradication of smallpox, MVA is a highly attenuated and replication-defective strain incapable of virion assembly and exerts potent immunostimulatory activity against antigens. Vaccination with MVA-MUC1-IL2 vaccine may stimulate the host immune system to mount a humoral and cytotoxic T lymphocyte (CTL) responses against tumor cells expressing MUC1, a tumor associated antigen, resulting in tumor cell lysis. Expression of IL-2 augments the specific CTL response against MUC1 expressing cells.
A Cremophor EL-free, albumin-stabilized nanoparticle formulation of the natural taxane paclitaxel with antineoplastic activity. Paclitaxel binds to and stabilizes microtubules, preventing their depolymerization and so inhibiting cellular motility, mitosis, and replication. This formulation solubilizes paclitaxel without the use of the solvent Cremophor, thereby permitting the administration of larger doses of paclitaxel while avoiding the toxic effects associated with Cremophor.
A non-neoplastic or neoplastic disorder which results from exposure to radiation. Examples of non-neoplastic disorders include dermatitis, enteritis, stomatitis, pneumonitis, and cerebritis. Examples of neoplastic disorders include myelodysplastic syndromes, leukemias, and sarcomas.
A preparation of plasma proteins derived from the pooled plasma of adult donors. Largely comprised of IgG antibodies, therapeutic immune globulin provides passive immunization by increasing the recipient's serum levels of circulating antibodies. IgG antibodies have multiple functions, including binding to and neutralizing bacterial toxins; opsonization of pathogens; activation of complement; and suppression of pathogenic cytokines and phagocytes through binding to CD5, interleukin-1a (IL-1a), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and T-cell receptors. Therapeutic immune globulin may diminish pathogenic mechanisms in some autoimmune diseases by binding to and inhibiting the activity of autoantibodies. (NCI04)
A recombinant replication-defective adenovirus which encodes the gene for the cytokine human interferon-beta (IFN-beta). Once inserted into and replicating in host tumor cells, recombinant adenovirus-hIFN-beta expresses human IFN-beta, which may stimulate an antiproliferative natural killer (NK) cell response against tumor cells and induce caspase-mediated tumor cell apoptosis. (NCI04)
A recombinant counterpart of tumor-associated KSA antigen (Ep-CAM), a type-I transmembrane glycoprotein cellular adhesion molecule with a molecular mass of 40 kDa, overexpressed on the majority of tumor cells of most human epithelia in a of variety of tumor tissues such as stomach, colon, pancreas, gall bladder, bile duct, mammary gland, breast, and lung carcinoma. It has been suggested to be involved in the differentiation, growth, and organization of epithelial cells within tissues under normal physiological conditions. The antigen has been used as a target for diagnosis and for passive and active immunotherapy of colorectal cancer. Immunization with KSA Glycoprotein elicits both humoral and Th1-associated cellular immune responses.
The colon and rectum are part of the large intestine. Colorectal cancer occurs when tumors form in the lining of the large intestine. It is common in both men and women. The risk of developing colorectal cancer rises after age 50. You're also more likely to get it if you have colorectal polyps, a family history of colorectal cancer, ulcerative colitis or Crohn's disease, eat a diet high in fat, or smoke. Symptoms of colorectal cancer include. -Diarrhea or constipation. -A feeling that your bowel does not empty completely. -Blood (either bright red or very dark) in your stool. -Stools that are narrower than usual. -Frequent gas pains or cramps, or feeling full or bloated. -Weight loss with no known reason. -Fatigue. -Nausea or vomiting. Because you may not have symptoms at first, it's important to have screening tests. Everyone over 50 should get screened. Tests include colonoscopy and tests for blood in the stool. Treatments for colorectal cancer include surgery, chemotherapy, radiation, or a combination. Surgery can usually cure it when it is found early. NIH: National Cancer Institute.
Multiple punctate calcifications in the dental pulp.
A tropical infectious disease found mainly in Africa that is caused by the filarial parasite ACANTHOCHEILONEMA. Symptoms include skin rashes, abdominal, chest, muscle, and joint pains, neurologic disorders, skin lumps, and elevated levels of white blood cells. The parasite is transmitted through the bite of small flies.
DYSENTERY caused by gram-negative rod-shaped enteric bacteria (ENTEROBACTERIACEAE), most often by the genus SHIGELLA. Shigella dysentery, Shigellosis, is classified into subgroups according to syndrome severity and the infectious species. Group A: SHIGELLA DYSENTERIAE (severest); Group B: SHIGELLA FLEXNERI; Group C: SHIGELLA BOYDII; and Group D: SHIGELLA SONNEI (mildest).
An allergy is an immune response or reaction to substances that are usually not harmful.
An optical condition in the eye where there is an error of refraction of light rays on the retina.
Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6)
Deficiency of PYRIDOXINE, one of the VITAMIN B 6 compounds. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).
The dihydrochloride salt of amonafide, an imide derivative of naphthalic acid. Amonafide intercalates into DNA and inhibits topoisomerase II, resulting in protein-associated strand breaks and impaired DNA and RNA synthesis.
Sjogren syndrome is an autoimmune disease that mainly affects the exocrine glands. It is clinically characterized by keratoconjunctivitis sicca and xerostomia (Goransson et al., 2006). See 200400 for association of Sjogren syndrome with achalasia in sisters.
Cerebral amyloid angiopathy (CAA), defined by the deposition of congophilic material in the vessels of the cortex and leptomeninges, is a major cause of intracerebral hemorrhage in the elderly (Vinters, 1987, Greenberg, 1998). Palsdottir et al. (1988) referred to the disorder in Icelandic patients as hereditary cystatin C amyloid angiopathy (HCCAA).
A speech disorder resulting in impaired utterance of sounds by the vocal folds.
A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia, and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives.
A breast carcinoma arising from the ducts. While ductal carcinomas can arise at other sites, this term is universally used to refer to carcinomas of the breast. Ductal carcinomas account for about two thirds of all breast cancers. Two types of ductal carcinomas have been described: ductal carcinoma in situ (DCIS) and invasive ductal carcinoma. The latter often spreads to the axillary lymph nodes and other anatomic sites. The two forms of ductal carcinoma often coexist.
A nonimmunologic, chemically induced type of photosensitivity.
A sudden flexion, extension or mixed extension-flexion of predominantly proximal and truncal muscles which is usually more sustained than a myoclonic movement but not as sustained as a tonic seizure.
VINCENT INFECTION where the lesions spread to the SOFT PALATE and OROPHARYNX.
Isolated patches of hardened skin (scleroderma).
Annular constrictions around the digits, limbs, or trunk, occurring congenitally (sometimes causing intrauterine autoamputation) and also associated with a wide variety of disorders. Constrictive amniotic bands are the result of primary amniotic rupture, which can lead to entanglement of fetal tissue (especially limbs) in fibrous amniotic strands.
A benign or malignant neoplasm that arises from or metastasizes to structures within the cranium. This includes meningeal and other tumors that occur in the spaces that surround the brain, and neoplasms of the brain.
agents of both drug and biological origin often used in immunotherapy to stimulate, potentiate, or depress the immune response; also used to inhibit or enhance specific subclasses of immunocytes.
A hypoglycemic reaction to overdosage of insulin, a skipped meal, or strenuous exercise in an insulin-dependent diabetic.
Abnormally high level of red blood cells in the blood.
An inflammatory lung disorder characterized by an increased number of eosinophils in the lungs. The majority of cases are idiopathic, without identifiable cause. In a minority of cases, medications, fungal infections, and environmental triggers have been implicated. It manifests as acute or chronic. Acute eosinophilic pneumonia is a severe and rapidly progressing pneumonia that may lead to respiratory failure requiring mechanical ventilation. Chronic eosinophilic pneumonia follows a slower course and manifests as fever, dyspnea, cough, and weight loss.
metabolic bone disease due to increased bone resorption resulting from the acidosis and secondary hyperparathyroidism of renal insufficiency.
Cervical squamous intraepithelial neoplasia characterized by the presence of maturation in the upper two-thirds of the squamous epithelium and mild nuclear atypia which is present in all epithelial layers. Mitotic figures are present in the basal third of the epithelium.
A rare adenocarcinoma arising from Skene gland. It presents as a periurethral or anterior vaginal submucosal mass. It is characterized by morphological features similar to prostate adenocarcinoma.
A laboratory test result indicating abnormally high concentration of non-protein nitrogen in the blood.
A member of the CXC chemokine family. This chemokine is one of the major mediators of the inflammatory response. This chemokine is secreted by several cell types including monocytes, macrophages, T-lymphocytes, fibroblasts, endothelial cells, and keratinocytes. It functions as a chemoattractant, and is also a potent angiogenic factor. (from LocusLink)
An orally active small molecule with potential antineoplastic activity. Although its mechanism of action has yet to be fully elucidated, HIF1-alpha inhibitor PX-478 appears to inhibit hypoxia-inducible factor 1-alpha (HIF1A) expression, which may result in decreased expression of HIF1A downstream target genes important to tumor growth and survival, a reduction in tumor cell proliferation, and the induction of tumor cell apoptosis. The inhibitory effect of this agent is independent of the tumor suppressor genes VHL and p53 and may be related to derangements in glucose uptake and metabolism due to inhibition of glucose transporter-1 (Glut-1).
The hydrochloride salt form of spirapril, a prodrug and non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Spirapril is converted in the body to its active metabolite spiraprilat. Spiraprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Spirapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A nucleoside reverse transcriptase inhibitor prodrug analog of guanosine.
A recombinant protein consisting of the hu14.18 monoclonal antibody fused to the cytokine interleukin-2 (IL2) with potential antineoplastic activity. The monoclonal antibody portion of the hu14.18-IL2 fusion protein binds to tumor cells expressing the GD2 antigen (melanoma, neuroblastoma and certain other tumors); the Fc component of the fusion protein antibody moiety and natural killer (NK) cells mediate antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDCC) towards GD2-expressing tumor cells. The localized IL2 moiety of the fusion protein stimulates NK and T-cell antitumor cellular immune responses.
A selective serotonin (5-HT) reuptake inhibitor (SSRI) and a 5-HT-1A receptor partial agonist, with antidepressant and anti-anxiety activities. Vilazodone inhibits the reuptake of serotonin from the synaptic cleft while stimulating the release of 5-HT into the synaptic cleft. This increases the concentration of 5-HT in the synaptic cleft and potentiates serotonergic neurotransmission in the central nervous system.
A 28-mer RNA aptamer covalently linked to two branched 20-kD polyethylene glycol (PEG) chains, with anti-angiogenic activity. Pegaptanib binds and blocks the activity of the extracellular vascular endothelial growth factor, specifically the 165-amino acid isoform (VEGF165). This prevents VEGF165 from binding to VEGF receptors, thereby blocking angiogenesis as well as preventing VEGF165-induced increases in vessel permeability. VEGF165 is preferentially involved in pathological ocular neovascularisation.
Compromise of blood supply to the anterior segment of the eye.
A plasma cell myeloma lacking clinical manifestations and organ impairment.
Abnormal enlargement of the cerebral ventricles.
A diagnostic reflex elicited by stimulation of the skin over the surface of the lateral malleolus of the foot. The Chaddock refelx is present if there is extension of one or more or all of the toes with or without fanning of them when the external inframalleolar skin is stimulated. The Chaddock sign, similar to the Babinski sign, is taken to be an indication of disease of the spinocortical (pyramidal) tract.
A pattern of reliance on religious beliefs and/or participation in rituals of a particular faith tradition, which can be strengthened.
The atherogenic lipoprotein phenotype (ALP) is a common heritable trait characterized by a preponderance of small, dense low density lipoprotein (LDL) particles (subclass pattern B), increased levels of triglyceride-rich lipoproteins, reduction in high density lipoprotein, and a 3-fold increased risk of myocardial infarction (summary by Nishina et al., 1992). The so-called atherogenic lipoprotein phenotype was shown by Austin et al. (1988) to be independently associated with an increased risk for coronary artery disease. Allayee et al. (1998) concluded, furthermore, that there is a genetically based association between familial combined hyperlipidemia (FCHL; 144250) and small, dense LDL particles and that the genetic determinants for LDL particle size are shared, at least in part, among FCHL families and the more general population at risk for coronary artery disease. Juo et al. (1998) concluded from a bivariate segregation analysis of small, dense LDL particles and elevated apolipoprotein B levels (APOB; 107730), which are commonly found together in members of FCHL families, that the 2 traits share a common major gene plus individual polygenic components. The common major gene was estimated to explain 37% of the variance of adjusted LDL particle size and 23% of the variance of adjusted apoB levels.
A hamartoma of lymph vessels that usually presents in childhood. It tends to increase in size with head-down posture and with the Valsalva manoeuvre. Superficial lesions are visible as transilluminable cystic spaces of the lid or conjunctiva that may also contain blood. Deep lesions may cause gradual proptosis or present acutely with orbital pain and reduced vision due to haemorrhage. [ISBN-13: 978-0199679980]
A type of lifestyle that lacks physical exercise, characterized by sitting, reading, watching television or using a computer for much of the day without vigorous physical exertion.
Infectious condition of the internal eye.
A rare non-encapsulated and poorly circumscribed lesion that usually affects the posterior neck. It is seen more frequently in men and is characterized by the presence of thick collagen fibers. It may recur but does not metastasize.
Inflammation of the lining of the ocular cavities, which results from a fungal infection.
An ethyl ester form of omega-3 fatty acid derived from fish oil, with activity in decreasing serum triglyceride levels. Although its mechanism of action isn't known, omega-3-acid ethyl esters may work by decreasing the amount of triglycerides and other fats made in the liver.
A pharmaceutical preparation of ezetimibe and simvastatin that is used in the treatment of HYPERCHOLESTEROLEMIA and HYPERLIPIDEMIAS.
Dorsiflexion of the big toe, sometimes accompanied by fanning of the other toes, elicited by stroking along the medial side of the tibia (the normal response would be no movement of the big toe).
A cyclopropanecarboxamide serotonin and norepinephrine reuptake inhibitor (SNRI) that is used in the treatment of FIBROMYALGIA.
A benign, well circumscribed sweat gland neoplasm with eccrine or apocrine differentiation. It usually presents as a solitary, dome-shaped papule, nodule, or plaque on acral sites. It is characterized by a proliferation of uniform basaloid cells in the dermis and it is associated with the presence of focal ductal and cystic structures. Complete excision is curative.
Acute myeloid leukemia characterized by the presence of abnormal bone marrow eosinophils and the characteristic cytogenetic abnormality inv(16)(p13.1q22) which results in the expression of the fusion protein CBFB-MYH11.
The oil extracted from the fruit peel of Citrus aurantifolia. Lime oil can be taken as an antioxidant and may help support immune health. Additionally, it is used as a flavoring agent.
A quinazoline derivative and ANTINEOPLASTIC AGENT that functions as a PROTEIN KINASE INHIBITOR for EGFR associated tyrosine kinase. It is used in the treatment of NON-SMALL CELL LUNG CANCER.
A synthetic or animal-derived form of insulin used in the treatment of diabetes mellitus. Therapeutic insulin is formulated to be short-, intermediate- and long-acting in order to individualize an insulin regimen according to individual differences in glucose and insulin metabolism. Therapeutic insulin may be derived from porcine, bovine or recombinant sources. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats and has anabolic effects on many types of tissues.
A paraganglioma that metastasizes to regional or distant anatomic sites. Extraadrenal paragangliomas have a higher tendency to metastasize, as compared to pheochromocytomas. Common sites of metastasis include the lymph nodes, lungs, bones, and liver.
An abnormal connection between arteries and veins, occurring within the renal vasculature, which can result in flank pain, and hematuria.
Failure of parents or caretakers to provide basic care and emotional support necessary for normal development.
An imperfection if the retina of the eye in association with detachment of the retina from its blood supply.
A recombinant, humanized anti-CD33 monoclonal antibody attached to the cytotoxic antitumor antibiotic calicheamicin. In this conjugate, the antibody binds to and is internalized by tumor cells expressing CD33 antigen (a sialic acid-dependent glycoprotein commonly found on the surface of leukemic blasts), thereby delivering the attached calicheamicin to CD33-expressing tumor cells. Calicheamicin binds to the minor groove of DNA, causing double strand DNA breaks and resulting in inhibition of DNA synthesis. (NCI04)
A sulfated oligosaccharide. PI-88 inhibits heparanase activity and heparan sulfate binding to fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF), resulting in decreased tumor proliferation, inhibition of angiogenesis, and inhibition of metastasis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=339562&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=339562&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C38690"" NCI Thesaurus)
Decreased number of granulocyte precursors in the bone marrow.
A recombinant form of the heterodimeric human anterior pituitary glycoprotein thyroid-stimulating hormone (TSH) with potential use in hormone replacement therapy. Recombinant TSH binds to TSH receptors on thyroid epithelial cells and stimulates TSH-dependent signaling pathways. This stimulates iodine uptake and organification, and induces synthesis and secretion of thyroglobulin (Tg), triiodothyronine (T3), and thyroxine (T4).
A condition characterized by development of symptoms while standing. It is an autonomic nervous system disorder and the symptoms are relieved once the person sits back down. Symptoms include heart palpitations, sweating, anxiety, lightheadedness, hyperpnea, anxiety, and blurred vision.
A reduction in the strength of the muscles of the pelvic floor.
A childhood disorder that has a neurological basis and manifests as a developmental disability.
A pulmonary disease in humans occurring in immunodeficient or malnourished patients or infants, characterized by DYSPNEA, tachypnea, and HYPOXEMIA. Pneumocystis pneumonia is a frequently seen opportunistic infection in AIDS. It is caused by the fungus PNEUMOCYSTIS JIROVECII. The disease is also found in other MAMMALS where it is caused by related species of Pneumocystis.
The usual amount of blood that is forced from the heart ventricle to produce cardiac output. Quantitatively, the ejection fraction is considered between 50% to 70%.
Inflammation of the alimentary part of the gastrointestinal system.
Increased plasma concentrations of chylomicrons, the large lipid droplet (up to 100 mm in diameter) of reprocessed lipid synthesized in epithelial cells of the small intestine and containing triacylglycerols, cholesterol esters, and several apolipoproteins.
Rupture of the umbilical cord during labor and delivery.
A form of MACULAR DEGENERATION also known as dry macular degeneration marked by occurrence of a well-defined progressive lesion or atrophy in the central part of the RETINA called the MACULA LUTEA. It is distinguishable from WET MACULAR DEGENERATION in that the latter involves neovascular exudates.
A clinical syndrome defined by MYOCARDIAL ISCHEMIA symptoms; persistent elevation in the ST segments of the ELECTROCARDIOGRAM; and release of BIOMARKERS of myocardial NECROSIS (e.g., elevated TROPONIN levels). ST segment elevation in the ECG is often used in determining the treatment protocol (see also NON-ST ELEVATION MYOCARDIAL INFARCTION).
Problem associated with the failure to achieve effective and consistent depolarization of the heart resulting from the electrical stimulus of the pacemaker.
An abnormal communication between the pharynx and another organ or anatomic site.
Alpha-methylacetoacetic aciduria, also known as 3-ketothiolase deficiency, is an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and 2-butanone.
A cutaneous, usually multifocal lesion in the penis characterized by the presence of verrucous papules. It is caused by human papillomavirus infection. Morphologically there is bowenoid dysplasia present. Progression to invasive carcinoma is infrequent.
A benign neoplasm that arises from the ciliated respiratory mucosa that lines the nasal cavity or paranasal sinuses. It results from the invagination and proliferation of epithelial cells in the underlying stroma. Clinical manifestations include nasal obstruction, epistaxis, and anosmia. It has the tendency to recur and extend to adjacent structures. Inverted papillomas are occasionally associated with the development or presence of carcinomas, usually squamous cell carcinomas.
Medical device failure or malfunction associated with device functions, including any deviations from documented specifications, requirements, and intended uses.
A syndrome characterized by persistent eosinophilia, for which no underlying cause can be found, and which is associated with signs of organ involvement and dysfunction. This term has often been applied to cases of chronic eosinophilic leukemia. (WHO, 2001)
A chimeric monoclonal antibody with potential antineoplastic activity. Volociximab binds to and inhibits the activity of alpha(5)beta(1) integrin, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis. (NCI05)
A formulation of polyethylene glycol (PEG) conjugated paclitaxel, a compound extracted from the Pacific yew tree Taxus brevifolia, with antineoplastic activity. Paclitaxel binds to and stabilizes tubulin molecules, thereby interfering with the dynamics of microtubule assembly/disassembly and resulting in the inhibition of cell division. This agent also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein B-cell Leukemia 2 (Bcl-2). Compared to paclitaxel alone, pegylated paclitaxel has an enhanced water solubility leading to an increase in bioavailability, and decreases its toxicity profile. Therefore, the pegylated formulation potentially supports delivery of higher doses of paclitaxel to the specific site.
An irradiated, autologous pancreatic cancer vaccine consisting of patient-specific pancreatic cancer cells genetically modified to secrete the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Upon vaccination, GVAX pancreatic cancer vaccine secretes GM-CSF. In turn, GM-CSF may stimulate the body's immune system against tumor cells by enhancing the activation of dendritic cells (DCs) and promoting antigen presentation to both B- and T-cells. In addition, GM-CSF promotes antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function.
Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph nodes with or without other lymph node regions on the same side of the diaphragm (IIE). Note: The number of lymph node regions involved may be indicated by a subscript (e.g., II3). (PDQ)
The reemergence of marginal zone lymphoma after a period of remission.
A formulation composed of DOTAP:cholesterol liposomal nanoparticles complexed with a plasmid expression cassette encoding human FUS1 protein, with potential antineoplastic activity. Upon administration, DOTAP:chol-Fus1 liposome complex accumulates mainly in the lungs and particularly in cancer cells. Upon transfer of the Fus1 gene into tumor cells, the expression of Fus1 may induce tumor cell apoptosis and suppress tumor cell proliferation. Fus1, a potent tumor-suppressor protein, is present in normal, healthy cells but often absent in certain cancer cells. DOTAP:cholesterol liposome is composed of cationic lipid dioleoyl-trimethylammonium propane (DOTAP) and cholesterol at a molar ratio of 1:1.
A chemotherapy drug combination consisting of everolimus and gefitinib. Everolimus is a proliferation inhibitor with immunosuppressive and anti-angiogenic properties. Gefitinib is an epidermal growth factor receptor (EGFR) inhibitor with anti-angiogenic activity. This combination chemotherapy may result in increased tumor cell death compared to the use of either agent alone. (NCI05)
A vaccine adjuvant containing CpG 7909, monophosphoryl lipid, and QS-21 with potential antineoplastic and immunostimulatory activities. CpG 7909 is a synthetic 24-mer oligonucleotide containing 3 CpG motifs that selectively targets Toll-like receptor 9 (TLR9), thereby activating dendritic and B cells and stimulating cytotoxic T cell and antibody responses against tumor cells bearing tumor antigens. Monophosphoryl lipid is a detoxified derivative of lipid A, a component of Salmonella minnesota lipopolysaccharide (LPS); this agent may enhance humoral and cellular responses to various antigens. QS-21 is a purified, naturally occurring saponin derived from the South American tree Quillaja saponaria Molina and exhibits various immunostimulatory activities. Combinations of monophosphoryl lipid and QS-21 may be synergistic in inducing humoral and cellular immune responses. (NCI05)
A radioconjugate consisting of sestamibi labeled with the positron-emitting isotope Tc 94m. Sestamibi is a synthetic molecule of the isonitrile family that diffuses through cell membranes and may preferentially accumulate within mitochondria. Technetium Tc 94m sestamibi may be used in tumor-imaging studies utilizing positron emission tomography (PET). (NCI05)
A giant cell glioblastoma occurring in adults.
An acute myeloid leukemia with t(16;16)(p13.1;q22) occurring in adults.
An acute myeloid leukemia with t(9;11)(p22.3;q23.3); MLLT3-KMT2A occurring in adults.
A cancer vaccine comprised of a recombinant vaccinia viral vector encoding the carcinoembryonic antigen (CEA), MUC-1 (mucin-1), a transmembrane glycoprotein secreted by glandular tissues, and TRICOM, comprised of the three co-stimulatory molecule transgenes B7-1, ICAM-1 and LFA-3. Upon administration, inalimarev may enhance CEA and MUC-1 presentation to antigen presenting cells (APC) and may activate a cytotoxic T lymphocyte (CTL) response against CEA- and MUC-1-expressing tumor cells.
A cancer vaccine comprised of a recombinant fowlpox viral vector encoding the carcinoembryonic antigen (CEA), MUC-1, a transmembrane glycoprotein secreted by glandular epithelial tissues, and TRICOM, comprised of three co-stimulatory molecule transgenes (B7-1, ICAM-1 and LFA-3). This agent may enhance CEA and MUC-1 presentation to antigen-presenting cells (APC) and may activate a cytotoxic T-cell response against CEA- and MUC-1-expressing tumor cells.
A vaccine consisting of a recombinant adenoviral vector encoding alpha fetoprotein. After vaccination, expressed alpha fetoprotein may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells that express alpha fetoprotein, resulting in tumor cell lysis. (NCI05)
A vaccine consisting of plasmid DNA encoding alpha fetoprotein. After vaccination, expressed alpha fetoprotein may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells that express alpha fetoprotein, resulting in tumor cell lysis. (NCI05)
A vaccine adjuvant consisting of a plasmid DNA encoding sargramostim (granulocyte-macrophage colony-stimulating factor). Upon administration, expressed sargramostim may stimulate a cytotoxic T cell response enhancing the host immune response to a concomitantly administered hepatocellular carcinoma vaccine. (NCI05)
An allogenic vaccine consisting of irradiated breast cancer cells transfected with the granulocyte macrophage-colony-stimulating factor (GM-CSF) gene. Upon vaccination, the genetically modified cells secrete GM-CSF, thereby potentiating a tumor-specific T cell response against breast cancer cell-asociated antigens.
A synthetic imidazoquinoline Toll-like receptor 7 (TLR7) agonist with immunostimulating and potential antitumor activities. TLR7 agonist 852A binds to and activates TLR7, thereby stimulating plasmacytoid dendritic cells (pDC) through the TLR7-MyD88-dependent signaling pathway. Activation of pDC results in secretion of interferon alpha, the production of proimflammatory cytokines, the upregulation of co-stimulatory molecules, and enhanced T and B-cell stimulatory responses.
A cell-based vaccine composed of irradiated tumor cells transduced with granulocyte-macrophage colony-stimulating factor (GM-CSF) and CD40-ligand (CD40L) genes. Upon administration, this vaccine may stimulate an anti-tumoral dendritic cell-mediated host immune response. (NCI05)
A cell-based vaccine composed of autologous tumor cells fused with Epstein-Barr virus-transformed B-lymphoblastoid cells. Upon administration, this vaccine may stimulate a cytotoxic T cell response against tumor cells, resulting in tumor cell lysis. (NCI05)
Grade III lymphomatoid granulomatosis that occurs during childhood.
The reemergence of grade III lymphomatoid granulomatosis in childhood after a period of remission.
The reemergence of grade I lymphomatoid granulomatosis after a period of remission.
The reemergence of grade II lymphomatoid granulomatosis after a period of remission.
Grade III lymphomatoid granulomatosis that occurs in adulthood.
The reemergence of grade III lymphomatoid granulomatosis in adulthood after a period of remission.
An orally bioavailable pan-HER tyrosine kinase inhibitor with potential antineoplastic activity. BMS-599626 inhibits human epidermal growth factor receptors (HER) HER1, HER2 and HER4, thereby inhibiting the proliferation of tumor cells that overexpress these receptors. (NCI05)
An orally bioavailable multiple-receptor tyrosine kinase inhibitor with potential antineoplastic activity. AMG 706 selectively targets and inhibits vascular endothelial growth factor (VEGFR), platelet-derived growth factor (PDGFR), kit, and Ret receptors, thereby inhibiting angiogenesis and cellular proliferation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=391228&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=391228&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48374"" NCI Thesaurus)
A cancer vaccine consisting of PEP-3, a synthetic peptide encompassing a tumor-specific mutated segment of the epidermal growth factor receptor type vIII (EGFRvIII), conjugated to the naturally-occurring immunoadjuvant keyhole limpet hemocyanin (KLH) with potential immunostimulating and antineoplastic activities. Upon administration, PEP-3-KLH conjugate vaccine may induce a cytotoxic immune response against tumor cells that overexpress EGFRvIII; this antitumoral immune response may involve antibody-dependent cellular cytotoxicity (ADCC).
A peptide cancer vaccine comprised of a peptide derived from the human melanoma antigen A3 (MAGE-A3), with potential immunostimulating and antineoplastic activities. Upon administration, MAGE-A3 peptide vaccine may stimulate the immune system to mount a cytotoxic T-cell (CTL) response against tumor cells expressing MAGE-A3, resulting in tumor cell lysis. MAGE-A3, a tumor-associated antigen (TAA), is overexpressed by a variety of cancer cell types.
A humanized monoclonal antibody directed against terminal complement protein C5. Eculizumab binds to terminal complement protein C5, thereby blocking C5 cleavage into pro-inflammatory components and blocking the complement-mediated destruction of paroxysmal nocturnal hemoglobinuria (PNH) red blood cells. (NCI05)
A chimeric monoclonal antibody directed against a primate-restricted N-linked carbohydrate epitope (glycotope) expressed on various human carcinomas with potential antineoplastic activity. Following binding, monoclonal antibody RAV12 disrupts sodium channels of tumor cells expressing this glycotope, resulting in cell and organelle swelling, loss of membrane integrity, and cell death. (NCI05)
A sustained-release formulation for inhalation in which the inorganic platinum (Pt) agent cisplatin is encapsulated in lipids, with potential antineoplastic activity. Upon inhalation of the sustained-release lipid inhalation targeting (SLIT) cisplatin into the lungs, this agent forms highly reactive, positively charged, Pt complexes, which covalently bind to nucleophilic groups in DNA, preferably at the N7 position of guanine bases. Pt complex binding introduces intrastrand and interstrand DNA cross-links, and DNA-Pt-protein cross-links. These cross-links result in apoptosis and cell growth inhibition of lung cancer cells. Encasement in liposomes prolongs cisplatin's efficacy when compared to intravenously administered cisplatin; inhalation of cisplatin improves its concentration at tumor sites in the lungs while minimizing its systemic toxicity.
A humanized monoclonal antibody directed against alpha fetoprotein with potential antineoplastic activity. Upon administration, monoclonal antibody HuAFP31 (mAb HuAFP31) binds to and stimulates a cytotoxic T lymphocyte (CTL) response against tumor cells that express alpha fetoprotein.
A radioimmunoconjugate comprised of the humanized monoclonal antibody tacatuzumab, directed against alpha fetoprotein, that is conjugated to the chelating agent tetraxetan and radiolabeled with the beta-emitting radioisotope Yttrium Y 90. Yttrium Y 90 tacatuzumab tetraxetan binds to tumor cells expressing alpha fetoprotein, thereby selectively delivering a cytotoxic dose of beta radiation.
A radioimmunoconjugate comprised of the humanized monoclonal antibody clivatuzumab, directed against the pancreatic cancer antigen MUC1, that is conjugated to the chelating agent tetraxetan and radiolabeled with the beta-emitting radioisotope Yttrium Y 90. Yttrium Y 90 clivatuzumab tetraxetan binds to tumor cells expressing MUC1 antigen, thereby selectively delivering a cytotoxic dose of beta radiation.
A humanized monoclonal antibody directed against the pancreatic cancer antigen MUC1 with potential antineoplastic activity. Monoclonal antibody HuPAM4 (mAb HuPAM4) binds to cells expressing MUC1 antigen; mAb HuPAM4 may be useful as a carrier for radioisotopes and other antineoplastic therapeutic agents. (NCI05)
A small molecule inhibitor of numerous tyrosine kinases (TKs) including fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), FMS-related tyrosine kinase 3 (FLT3), and SRC, with potential antineoplastic activity. Upon administration, XL999 binds to and inhibits the activity of these TKs, thereby preventing both the activation of downstream signaling pathways and the proliferation of tumor cells overexpressing these TKs. FGFR, VEGFR, PDGFR, FLT-3, and SRC are upregulated in a variety of cancer cell types and play key roles in tumor cell proliferation, angiogenesis, and metastasis.
An indole ether quinazoline derivative with antineoplastic properties. Competing with adenosine triphosphate, AZD2171 binds to and inhibits all three vascular endothelial growth factor receptor (VEGF-1,-2,-3) tyrosine kinases, thereby blocking VEGF-signaling, angiogenesis, and tumor cell growth. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=425596&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=425596&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48379"" NCI Thesaurus)
A cell-based vaccine composed of autologous dendritic cells (DCs) pulsed with lysates from heat-treated allogeneic melanoma tumor cells. Upon administration, this vaccine may stimulate anti-tumoral cytotoxic T-cell and antibody responses to melanoma cells bearing shared melanoma antigens such as MelanA/MART-1, gp100, MAGE3, resulting in tumor cell lysis.
A cancer vaccine consisting of a recombinant vaccinia viral vector encoding an immunogenic peptide derived from the cancer-testis antigen NY-ESO-1, an antigen found in normal testis and various tumors, including bladder, breast, hepatocellular, melanoma, and prostate cancers. Vaccination with recombinant vaccinia NY-ESO-1 peptide vaccine may stimulate the host immune system to mount a humoral and cytotoxic T lymphocyte (CTL) response against tumor cells expressing NY-ESO-1 antigen, resulting in tumor cell lysis. (NCI05)
A cancer vaccine consisting of a recombinant fowlpox virus vector encoding an immunogenic peptide derived from the cancer-testis antigen NY-ESO-1, an antigen found in normal testis and various tumors, including bladder, breast, hepatocellular, melanoma, and prostate cancers. Vaccination with NY-ESO-1 peptide vaccine may stimulate the host immune system to mount a humoral and cytotoxic T lymphocyte (CTL) response against tumor cells expressing NY-ESO-1 antigen, resulting in tumor cell lysis. (NCI05)
A monoclonal antibody directed against the CD20 antigen with potential antineoplastic activity. Monoclonal antibody hA20 (mAb hA20) is a fully humanized antibody that targets the CD20 antigen, a hydrophobic transmembrane protein located on normal pre-B and mature B lymphocytes. Following binding, mAb hA20 triggers a complement-dependent cell lysis and antibody-dependent cell-mediated cytotoxicity in cells overexpressing CD20. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=428486&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=428486&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48406"" NCI Thesaurus)
An endogenous pentapeptide with potential antineoplastic and antiangiogenic activities. Opioid growth factor (OGF) binds to and activates the OGF receptor, present on some tumor cells and vascular cells, thereby inhibiting tumor cell proliferation and angiogenesis. (NCI05)
A radiopharmaceutical comprised of the thymidine analog, 5-iodo-2-deoxyuridine (idoxuridine), labeled with the positron emitter iodine I 124. After incorporation into tumor cell DNA, positron emission tomography (PET) is used to image iodine I 124 localized to tumor cells for determining and monitoring tumor burden.
A cancer vaccine comprised of a synthetic peptide with an amino acid sequence corresponding to positions 154-163 of the amino acid sequence for prostate-specific antigen (PSA) with a leucine substitution at position 155. Upon administration, PSA:154-163 (155L) peptide vaccine may elicit a cytotoxic T-cell response against tumor cells that express PSA. (NCI05)
An ependymal tumor of the central nervous system occurring in adults.
An oligodendroglial tumor of the central nervous system occurring in adults.
A radioimmunoconjugate consisting of the iodine 131-radiolabeled murine IgG1 monoclonal antibody 8H9 directed against the surface immunomodulatory glycoprotein 4Ig-B7-H3 with potential radioimaging and radioimmunotherapeutic uses. Iodine I 131 monoclonal antibody 8H9 binds to 4Ig-B7-H3 (human B7-H3 with 4 Ig-like domains) and may be used to radioimage and/or destroy tumor cells that express tenascin. 4Ig-B7-H3 inhibits T-cell activation and the production of effector cytokines such as interferon-gamma and interleukin-4; it is expressed on the cell membranes of a wide variety of tumors of neuroectodermal, mesenchymal and epithelial origin and is highly expressed on monocyte-derived dendritic cells (mdDCs). In vitro, it has been shown that monoclonal antibody-mediated masking of 4Ig-B7-H3 on neuroblastoma cells resulted in the enhancement of natural killer (NK)-mediated lysis of target cells.
A cell-based vaccine composed of previously frozen autologous antigen-presenting peripheral blood mononuclear cells (enriched for a dendritic cell fraction) that have been exposed to a recombinant protein consisting of granulocyte-macrophage colony-stimulating factor (GM-CSF) fused to prostatic-acid phosphatase (PAP), a protein expressed by prostate cancer cells. Upon administration, the vaccine may stimulate an antitumor T-cell response against tumor cells expressing PAP.
A peptide vaccine comprised of synthetic HLA-A2- and HLA-A3-binding peptides, derived from amino acid sequences of fibroblast growth factor-5 (FGF-5), combined with the adjuvant Montanide ISA-51 with potential antineoplastic activity. HLA-A2, A3-restricted FGF-5 peptides contain motifs recognized by the MHC class I molecules HLA-A2 and HLA-A3 and may stimulate a cytotoxic T-cell response against tumor cells that overexpress FGF-5. Montanide ISA-51, a stabilized water-in-oil emulsion adjuvant containing mineral oil with mannide oleate added as a surfactant, non-specifically stimulates cell-mediated immune responses to antigens.
A cancer vaccine comprised of synthetic peptides corresponding to naturally-occurring peptides derived from ovarian cancer cell antigens. Ovarian cancer peptide vaccine may elicit a cytotoxic T-cell response against tumor cells expressing the related ovarian cancer cell antigens. (NCI05)
An orally bioavailable indolocarbazole derivative with antineoplastic properties. Lestaurtinib inhibits autophosphorylation of FMS-like tyrosine kinase 3 (FLT3), resulting in inhibition of FLT3 activity and induction of apoptosis in tumor cells that overexpress FLT3. (NCI05)
Malignant neoplasm originating from mast cells.
An infectious process involving the endocardial layer of the heart.
An intraepithelial carcinoma arising from any part of the digestive system without evidence of invasion.
A finding that generally has features of degeneration and necrosis.
Vaccines or candidate vaccines used to prevent infection with DENGUE VIRUS. These include live-attenuated, subunit, DNA, and inactivated vaccines.
Vaccines or candidate vaccines used to prevent infection with LEISHMANIA.
No inquiry was made to gather this information.
An indication that a question was asked and the response is unknown.
The condition existing when an order or judgement is considered temporary until either a specified period of time has passed or specific information is provided to assist in rendering a permanent decision.
A marital status in which a voidable marriage is legally declared null and void, as though it never existed. Specific grounds for annullment vary within the presiding jurisdiction, whether geographic or religious.
Indicates a person who is a member of an unmarried couple, including same sex couples, living together in longstanding relationships, that are registered or unregistered.
A type of living arrangement or mating system in which at least one member of a relationship has more than one mate.
A class of viral vaccines based on adenovirus genome which was engineered to harbor gene of therapeutic interest, and were to be used in vaccination against cancers.
Extent to which body weight, muscle, and fat are congruent to height, frame, gender, and age
Asymptomatic, intervention not indicated
Symptomatic, intervention not indicated; change in medication initiated
Life-threatening consequences; urgent intervention indicated
Symptomatic; non-urgent medical intervention indicated
An adverse event characterized by premature atrial contractions of the heart caused by signals originating from ectopic atrial sites or the atrioventricular node.
Non-urgent medical intervention indicated
Symptomatic, urgent intervention indicated
Life-threatening consequences; hemodynamic compromise
Adult: Systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg; Pediatric: Systolic/diastolic BP >90th percentile but< 95th percentile; Adolescent: BP >= 120/80 even if < 95th percentile
Adult: Systolic BP 140-159 mm Hg or diastolic BP 90-99 mm Hg if previously WNL; change in baseline medical intervention indicated; recurrent or persistent (>=24 hrs); symptomatic increase by >20 mm Hg (diastolic) or to >140/90 mm Hg; monotherapy indicated initiated; Pediatric and adolescent: Recurrent or persistent (>=24 hrs) BP >ULN; monotherapy indicated; systolic and /or diastolic BP between the 95th percentile and 5 mmHg above the 99th percentile; Adolescent: Systolic between 130-139 or diastolic between 80-89 even if < 95th percentile
Adult: Systolic BP >=160 mm Hg or diastolic BP >=100 mm Hg; medical intervention indicated; more than one drug or more intensive therapy than previously used indicated; Pediatric and adolescent: Systolic and/or diastolic > 5 mmHg above the 99th percentile
Adult and Pediatric: Life-threatening consequences (e.g., malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis); urgent intervention indicated
Medical intervention indicated; hospitalization indicated
Life-threatening consequences and urgent intervention indicated
Symptomatic due to drop in ejection fraction responsive to intervention
Refractory or poorly controlled heart failure due to drop in ejection fraction; intervention such as ventricular assist device, intravenous vasopressor support, or heart transplant indicated
Severe with symptoms at rest or with minimal activity or exertion; intervention indicated; new onset of symptoms
Life-threatening consequences; urgent intervention indicated (e.g., continuous IV therapy or mechanical hemodynamic support)
Asymptomatic, ECG or physical findings (e.g., rub) consistent with pericarditis
Symptomatic pericarditis (e.g., chest pain)
Pericarditis with physiologic consequences (e.g., pericardial constriction)
Minimal dyspnea; findings on physical exam or other evaluation
Moderate dyspnea, cough; requiring evaluation by cardiac catheterization and medical intervention
Severe symptoms, associated with hypoxia, right heart failure; oxygen indicated
Life-threatening airway consequences; urgent intervention indicated (e.g., tracheotomy or intubation)
Symptomatic without signs of heart failure
Symptomatic heart failure or other cardiac symptoms, responsive to intervention; new onset of symptoms
Refractory heart failure or other poorly controlled cardiac symptoms
A disorder characterized by impairment of right ventricular function associated with low ejection fraction and a decrease in motility of the right ventricular wall.
Asymptomatic with laboratory (e.g., BNP [B-Natriuretic Peptide ]) or cardiac imaging abnormalities
Symptoms with moderate activity or exertion
Life-threatening consequences; urgent intervention indicated (e.g., ventricular assist device); heart transplant indicated
An unfavorable feeling of fatigue temporally associated with the use of a medical treatment or procedure.
Fatigue not relieved by rest; limiting instrumental ADL
Fatigue not relieved by rest, limiting self care ADL
<=28 degrees C; 82.4 degrees F; life-threatening consequences (e.g., coma, hypotension, pulmonary edema, acidemia, ventricular fibrillation)
Mild difficulty falling asleep, staying asleep or waking up early
Moderate difficulty falling asleep, staying asleep or waking up early
Severe difficulty in falling asleep, staying asleep or waking up early
Loss of appetite without alteration in eating habits
Oral intake decreased without significant weight loss, dehydration or malnutrition
Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
Life-threatening consequences; urgent invasive intervention indicated
A disorder characterized by a necrotic process occurring in the peritoneum.
Tube feeding or TPN indicated; invasive intervention indicated
Life-threatening consequences; urgent operative intervention indicated
Inability to aliment adequately by GI tract; invasive intervention indicated; tube feeding or TPN indicated
A disorder characterized by a necrotic process occurring in the rectal wall.
Asymptomatic; clinical or diagnostic observations only; intervention not indicated
Symptomatic; altered GI function; IV fluids indicated <24 hrs
Symptomatic and severely altered GI function; tube feeding, TPN or hospitalization indicated; non-emergent operative intervention indicated
Symptomatic; altered GI function; limiting instrumental ADL; naso-gastric tube indicated
Hospitalization indicated; invasive intervention indicated; limiting self care ADL; long intestinal tube indicated
Symptomatic; altered GI function; limiting instrumental ADL
Hospitalization indicated; invasive intervention indicated; limiting self care ADL
Mild symptoms; intervention not indicated
Moderate symptoms; intervention indicated
Transfusion indicated; invasive intervention indicated; hospitalization
Life-threatening consequences; intubation or urgent intervention indicated
A disorder characterized by bleeding from the pleural cavity.
Asymptomatic; mild hemorrhage confirmed by thoracentesis
Symptomatic or associated with pneumothorax; chest tube drainage indicated
>1000 ml of blood evacuated; persistent bleeding (150-200 ml/hr for 2-4 hr); persistent transfusion indicated; elective operative intervention indicated; hospitalization
A disorder characterized by bleeding from the trachea.
Symptomatic; medical intervention indicated
Severe symptoms; invasive intervention indicated
Enzyme elevation; radiologic findings only
Severe pain; vomiting; medical intervention indicated (e.g., analgesia, nutritional support)
ANC <1000/mm3 with a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >=38 degrees C (100.4 degrees F) for more than one hour
New onset seizures (partial or generalized); multiple seizures despite medical intervention
Life-threatening consequences; prolonged repetitive seizures
Moderate symptoms; limiting instrumental ADL
Symptomatic; moderate decrease in visual acuity (best corrected visual acuity 20/40 and better or 3 lines or less decreased vision from known baseline); glare symptoms affecting instrumental ADL
Symptomatic with marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or more than 3 lines of decreased vision from known baseline, up to 20/200); limiting self care ADL
Less than 8 mmHg of elevated intraocular pressure (EIOP); no visual field deficit
EIOP which can be reduced to 21 mmHg or under with topical medications and no visual field deficit
Visual field deficit within the central 10 degrees of the visual field in the affected eye
A disorder characterized by inflammation to the cornea of the eye.
Symptomatic; moderate decrease in visual acuity (best corrected visual acuity 20/40 and better or 3 lines or less decreased vision from known baseline)
Symptomatic with marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or more than 3 lines of decreased vision from known baseline, up to 20/200); corneal ulcer; limiting self care ADL
Perforation; best corrected visual acuity of 20/200 or worse in the affected eye
Macular sparing rhegmatogenous detachment
Macula-off rhegmatogenous retinal detachment
Asymptomatic; clinical or diagnostic observations only
Symptomatic; moderate decrease in visual acuity (best corrected visual acuity 20/40 and better or 3 lines or less decreased vision from known baseline); limiting instrumental ADL
Best corrected visual acuity of 20/200 or worse in the affected eye
Anterior uveitis with 3+ or greater cells; intermediate posterior or pan-uveitis
A disorder characterized by visual perception of unclear or fuzzy images.
Symptomatic with marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or more than 3 lines of decreased vision from known baseline, up to 20/200); limiting self care ADL; vitrectomy indicated
Moderate pain; limiting instrumental ADL
Present with radiologic findings; intubation not indicated
Life-threatening respiratory or hemodynamic compromise; intubation or urgent intervention indicated
Altered eating habits; coughing or choking episodes after eating or swallowing; medical intervention indicated (e.g., suction or oxygen)
Dyspnea and pneumonia symptoms (e.g., aspiration pneumonia); hospitalization indicated; unable to aliment orally
Symptomatic (e.g., dyspnea, cough); medical intervention indicated (e.g., chest physiotherapy, suctioning); bronchoscopic suctioning
Supplemental oxygen indicated; hospitalization or elective operative intervention indicated (e.g., stent, laser)
Symptomatic; medical intervention indicated (e.g., fat-restricted diet); thoracentesis or tube drainage indicated
Severe symptoms; elective operative intervention indicated
Mild symptoms; nonprescription intervention indicated
Moderate symptoms, medical intervention indicated; limiting instrumental ADL
Shortness of breath with moderate exertion
Shortness of breath with minimal exertion; limiting instrumental ADL
Shortness of breath at rest; limiting self care ADL
Symptomatic, invasive intervention not indicated
Decreased oxygen saturation with exercise (e.g., pulse oximeter <88%); intermittent supplemental oxygen
Decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 <=55 mm Hg)
Life-threatening airway compromise; urgent intervention indicated (e.g., tracheotomy or intubation)
Sclerosis and/or operative intervention indicated; hospitalization indicated
Occasional (e.g., with coughing, sneezing, etc.), pads not indicated
Spontaneous; pads indicated; limiting instrumental ADL
Intervention indicated (e.g., clamp, collagen injections); operative intervention indicated; limiting self care ADL
Symptomatic; elective intervention indicated
Blockage of the normal flow of the contents of the spermatic cord.
Blockage of the normal flow of the sperm in the vas deferens.
Life-threatening consequences; organ failure; urgent operative intervention indicated
A rupture of the fallopian tube wall due to tubal pregnancy, or other traumatic or pathologic processes.
Life-threatening consequences; urgent operative intervention indicated (e.g., organ resection)
A rupture in the kidney due to traumatic or pathologic processes.
An opening in the wall of the spermatic cord.
A rupture in the wall of the vas deferens.
A disorder characterized by accumulation of urine within the bladder because of the inability to urinate.
Urinary, suprapubic or intermittent catheter placement not indicated; able to void with some residual
Placement of urinary, suprapubic or intermittent catheter placement indicated; medication indicated
Elective invasive intervention indicated; substantial loss of affected kidney function or mass
Decrease in erectile function (frequency or rigidity of erections) but intervention not indicated (e.g., medication or use of mechanical device, penile pump)
Decrease in erectile function (frequency/rigidity of erections), erectile intervention indicated, (e.g., medication or mechanical devices such as penile pump)
Decrease in erectile function (frequency/rigidity of erections) but erectile intervention not helpful (e.g., medication or mechanical devices such as penile pump); placement of a permanent penile prosthesis indicated (not previously present)
Symptomatic (e.g., pain or psychosocial impact)
Mild vaginal dryness not interfering with sexual function
Moderate vaginal dryness interfering with sexual function or causing frequent discomfort
Fluid retention; <3 kg of weight gain; intervention with fluid restriction and/or diuretics indicated
Moderate signs or symptoms; steroids indicated
Severe symptoms; hospitalization indicated
Life-threatening consequences; ventilatory support indicated
A finding of damage to the inferior vena cava.
Asymptomatic diagnostic finding; intervention not indicated
Symptomatic; repair or revision not indicated
Severe symptoms; limiting self care ADL; repair or revision indicated
5 to <10% from baseline; intervention not indicated
10-<20% from baseline; nutritional support indicated
>=20% from baseline; tube feeding or TPN indicated
Covering <10% BSA; associated with telangiectasias or changes in skin color
Covering 10-30% BSA; associated with striae or adnexal structure loss
Minimal symptoms; intervention not indicated
Medical intervention; minimal debridement indicated
Moderate to major debridement or reconstruction indicated
Severe symptoms; limiting self care ADL; intervention indicated
Covering <10% BSA and no associated erythema or pruritus
Covering 10-30% BSA and associated with erythema or pruritus; limiting instrumental ADL
Covering >30% BSA and associated with pruritus; limiting self care ADL
A disorder characterized by a decrease in density of hair compared to normal for a given individual at a given age and body location.
Hair loss of <50% of normal for that individual that is not obvious from a distance but only on close inspection; a different hair style may be required to cover the hair loss but it does not require a wig or hair piece to camouflage
Hair loss of >=50% normal for that individual that is readily apparent to others; a wig or hair piece is necessary if the patient desires to completely camouflage the hair loss; associated with psychosocial impact
Painless erythema and erythema covering <10% BSA
Erythema covering >30% BSA and erythema with blistering; photosensitivity; oral corticosteroid therapy indicated; pain control indicated (e.g., narcotics or NSAIDs)
A disorder characterized by an intense itching sensation.
Mild or localized; topical intervention indicated
Widespread and intermittent; skin changes from scratching (e.g., edema, papulation, excoriations, lichenification, oozing/crusts); oral intervention indicated; limiting instrumental ADL
Widespread and constant; limiting self care ADL or sleep; systemic corticosteroid or immunosuppressive therapy indicated
Telangiectasias covering >=10% BSA; associated with psychosocial impact
A disorder characterized by an itchy skin eruption characterized by wheals with pale interiors and well-defined red margins.
Urticarial lesions covering <10% BSA; topical intervention indicated
Urticarial lesions covering 10-30% BSA; oral intervention indicated
Urticarial lesions covering >30% BSA; IV intervention indicated
Moderate symptoms; medical intervention indicated
Oral intake altered without significant weight loss or malnutrition; oral nutritional supplements indicated
Associated with significant weight loss or malnutrition (e.g., inadequate oral caloric and/or fluid intake); tube feeding or TPN indicated
Occasional or intermittent symptoms; occasional use of stool softeners, laxatives, dietary modification, or enema
Persistent symptoms with regular use of laxatives or enemas; limiting instrumental ADL
Obstipation with manual evacuation indicated; limiting self care ADL
Increased oral fluids indicated; dry mucous membranes; diminished skin turgor
A disorder in the gingival tissue around the teeth.
Gingival recession or gingivitis; limited bleeding on probing; mild local bone loss
Moderate gingival recession or gingivitis; multiple sites of bleeding on probing; moderate bone loss
Spontaneous bleeding; severe bone loss with or without tooth loss; osteonecrosis of maxilla or mandible
Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline
Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental ADL
Increase of >=7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL
Rectal discomfort, intervention not indicated
Symptomatic (e.g., rectal discomfort, passing blood or mucus); medical intervention indicated; limiting instrumental ADL
Severe symptoms; fecal urgency or stool incontinence; limiting self care ADL
Symptomatic (e.g., abdominal pain, fever, change in bowel habits with ileus); peritoneal signs
Severely altered GI function; TPN indicated; elective invasive intervention indicated
Symptomatic; altered GI function (e.g., altered dietary habits, vomiting, diarrhea)
Outpatient IV hydration; medical intervention indicated
Tube feeding, TPN, or hospitalization indicated
1+ proteinuria; urinary protein > or = to ULN-<1.0 g/24 hrs
Adult: 2+ and 3+ proteinuria; urinary protein 1.0-<3.5 g/24 hrs; Pediatric: Urine P/C (Protein/Creatinine) ratio 0.5-1.9
Adult: Urinary protein >=3.5 g/24 hrs; 4+ proteinuria; Pediatric: Urine P/C (Protein/Creatinine) ratio >1.9
Severe symptoms; limiting self care ADL; elective operative intervention indicated
Fibrotic degeneration of the deep connective tissues.
Symptomatic but non-displaced; immobilization indicated
Severe symptoms; displaced or open wound with bone exposure; limiting self care ADL; operative intervention indicated
Severe symptoms; limiting self care ADL; invasive intervention indicated
Severe arthralgia or arthritis; extensive rash; steroids or IV fluids indicated
Moderate symptoms, medical intervention indicated
Severe symptoms, medical intervention indicated (e.g., steroids)
Life-threatening consequences; evidence of peripheral or visceral ischemia; urgent intervention indicated
A disorder characterized by laboratory test results that indicate widespread erythrocyte cell membrane destruction.
Laboratory evidence of hemolysis only (e.g., direct antiglobulin test; DAT; Coombs'; schistocytes; decreased haptoglobin)
Evidence of hemolysis and >=2 g decrease in hemoglobin
Transfusion or medical intervention indicated (e.g., steroids)
Moderate symptoms; intervention not indicated
Periods of asystole; non-urgent medical management indicated
A disorder characterized by a dysrhythmia with a progressively lengthening PR interval prior to the blocking of an atrial impulse. This is the result of intermittent failure of atrial electrical impulse conduction through the atrioventricular (AV) node to the ventricles.
Symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker)
Symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker); new onset
A longer than normal interval (corrected for heart rate) between the Q and T waves in the heart's cycle. Prolonged QTc can cause premature action potentials during late phase depolarizations thereby leading to ventricular arrhythmias and ventricular fibrillations.
Symptomatic, urgent intervention indicated; device (e.g., pacemaker); ablation; new onset
Life-threatening consequences; embolus requiring urgent intervention
Symptomatic, urgent intervention indicated; device (e.g., pacemaker); ablation
A disorder characterized by difficulty in swallowing.
Symptomatic and altered eating/swallowing
Severely altered eating/swallowing; tube feeding, TPN, or hospitalization indicated
Symptomatic; altered eating/swallowing; oral supplements indicated
A disorder characterized by an abnormal communication between the pharynx and another organ or anatomic site.
Moderate; persistent; psychosocial sequelae
A disorder characterized by inflammation of the stomach.
Symptomatic; altered GI function; medical intervention indicated
Severely altered eating or gastric function; TPN or hospitalization indicated
Symptomatic; banding or medical intervention indicated
A disorder characterized by failure of the ileum to transport intestinal contents.
Asymptomatic and radiologic observations only
Symptomatic; altered GI function; bowel rest indicated
Severely altered GI function; TPN indicated; tube placement indicated
Altered diet; oral intervention indicated
Inability to aliment adequately; TPN indicated
No breast development by age 13 yrs for females; testes volume of <3 cc or no Tanner Stage 2 development by age 14.5 yrs for males
No breast development by age 14 yrs for females; no increase in testes volume or no Tanner Stage 2 by age 16 yrs for males; hormone replacement indicated
Physical signs and biochemical markers of puberty for females <8 years and males <9 years
Minimally invasive evacuation or aspiration indicated
Transfusion; invasive intervention indicated
A disorder characterized by bleeding from the mouth.
Self-limited; intervention not indicated
Analgesics and hematocrit monitoring indicated
A disorder characterized by bleeding from the uterus.
Mild cough or trace hemoptysis; laryngoscopic findings
Life-threatening consequences; urgent intervention indicated (e.g., tracheotomy or intubation)
A disorder characterized by bleeding from the mediastinum.
Mild symptoms; intervention not indicated; radiologic evidence only
A disorder characterized by bleeding from the pharynx.
Moderate pain associated with weakness; pain limiting instrumental ADL
Pain associated with severe weakness; limiting self care ADL
Adult: Radiologic evidence of osteoporosis or Bone Mineral Density (BMD) t-score -1 to -2.5 (osteopenia); Pediatric: Radiologic evidence of low BMD with z score of <= -2.0 and no history of significant fractures
Adult: BMD t-score < -2.5; loss of height <2 cm; therapy to improve BMD indicated; limiting instrumental ADL; Pediatric: Low BMD (z-score <= -2.0) and significant fracture history (defined as a long bone fracture of the lower extremity, vertebral compression, 2 or more long bone fractures of the upper extremities); therapy to improve BMD indicated
Adult: Loss of height >=2 cm; hospitalization indicated; limiting self care ADL; Pediatric: Limiting self care ADL
Symptomatic; simple aspiration indicated
Symptomatic, elective invasive intervention indicated
A necrotic process affecting the soft tissues of the head.
Local wound care; medical intervention indicated (e.g., dressings or topical medications)
Operative debridement or other invasive intervention indicated (e.g., tissue reconstruction, flap, or grafting)
A necrotic process affecting the soft tissues of the neck.
A necrotic process affecting the soft tissues of the pelvis.
A disorder characterized by lack of ability to open the mouth fully due to a decrease in the range of motion of the muscles of mastication.
Decreased ROM (range of motion) without impaired eating
Decreased ROM requiring small bites, soft foods or purees
Decreased ROM with inability to adequately aliment or hydrate orally
Severe symptoms; limiting self care ADL; mechanical assistance indicated
Mild cognitive disability; not interfering with work/school/life performance; specialized educational services/devices not indicated
Moderate cognitive disability; interfering with work/school/life performance but capable of independent living; specialized resources on part time basis indicated
Severe cognitive disability; significant impairment of work/school/life performance
Moderate disorientation; limiting instrumental ADL
Severe disorientation; limiting self care ADL
Mild unsteadiness or sensation of movement
Moderate unsteadiness or sensation of movement; limiting instrumental ADL
Severe unsteadiness or sensation of movement; limiting self care ADL
Severe symptoms or neurological deficit; intervention indicated
Moderate memory impairment; limiting instrumental ADL
Severe memory impairment; limiting self care ADL
Severe agitation; hospitalization not indicated
Severe symptoms; limiting self care ADL; hospitalization indicated
Moderate depressive symptoms; limiting instrumental ADL
Severe depressive symptoms; limiting self care ADL; hospitalization not indicated
Life-threatening consequences, threats of harm to self or others; hospitalization indicated
Asymptomatic; mild signs (e.g., Babinski's reflex or Lhermitte's sign)
Moderate weakness or sensory loss; limiting instrumental ADL
Severe weakness or sensory loss; limiting self care ADL
A finding indicating the presence of multiple pouches, usually in the colonic or gastric wall.
An adverse event marked by a change in FEV1 lung function.
Functional anomaly of the kidney persisting for at least three months. [Eurenomics:ewuehl]
A childhood disorder characterized by difficulty initiating and maintaining sleep due to negative sleep associations, refusal to go to bed, and/or repeated attempts to delay bedtime.
A complex translational motion of the sacrum in its relationship to the innominates. (Sometimes described as a sidebending in one direction and rotation in the opposite direction. Alternatively described as a unilateral movement along the arc of the L-shaped curve of the sacroiliac joint.)
Rib motion of ribs 11 and 12 characterized by single joint motion; analogous to internal and external rotation.
Impaired or altered function of the cranial region.
1. A physiologic function occurring in the sacrum during ambulation and forward bending. 2. A sacral somatic dysfunction around an oblique axis in which a torque occurs between the sacrum and innominates. The L5 vertebra rotates in the opposite direction of the sacrum. 3. If the L5 does not rotate opposite to the sacrum, L5 is termed maladapted.4. Other terms for this maladaption include: rotations about an oblique axis, anterior or posterior sacrum and a torsion with a non-compensated L5 (Archaic use).
A somatic dysfunction in which the anterior superior iliac spine (ASIS) and posterior superior iliac spines (PSIS) are superior to the contralateral landmarks. The innominate (os coxa) moves more freely in a superior direction and is restricted from movement in an inferior direction.
Any agent that inhibits calcineurin (protein phosphatase 3; PPP3), a serine/threonine protein phosphatase dependent on calcium and calmodulin, with immunosuppressant activity. Inhibition of calcineurin prevents dephosphorylation of the transcription factor nuclear factor of activated T-cells, cytoplasmic (NFATc), which prevents its translocation to the nucleus and the subsequent induction of the expression of interleukin-2 (IL-2). This prevents IL-2-mediated proliferation and activation of T-cells, and T-lymphocyte-mediated immune responses.
A sacral somatic dysfunction described as a superior shear of one side of the sacrum resulting in a shallow (full) sacral sulcus and ipsilateral superior-anterior inferolateral angle of the sacrum.
A somatic dysfunction in which movement or position of one or several ribs is altered or disrupted.For example, an elevated rib is one held in a position of inhalation such that motion toward inhalation is freer, and motion toward exhalation is restricted. A depressed rib is one held in a position of exhalation such that motion toward exhalation is freer, and there is a restriction in inhalation.
1. A sacral somatic dysfunction that involves rotation of the sacrum about a middle transverse axis such that the sacral base has moved anteriorly between the pelvic bones. Forward movement of the sacral base is freer, backward movement is restricted and both sulci are deep. 2. The reverse of bilateral sacral extension.
Lens of the eye is smaller than normal and spherically shaped.
Impaired or altered function of the cervical region.
Fleck corneal dystrophy (CFD) is a rare autosomal dominant disease characterized by numerous tiny, dot-like white flecks scattered in all layers of the corneal stroma. Typically, the stroma located in between the flecks is clear, and the endothelium, the epithelium, Bowman layer, and Descemet membrane are normal. Patients are usually asymptomatic with normal vision, yet a small number of patients report the sensation of a minor photophobia. The flecks in CFD can appear as early as 2 years of age, or sometimes even at birth, and appear not to progress significantly throughout life. Histologically, the corneal flecks appear to correspond to abnormal keratocytes swollen with membrane-limited intracytoplasmic vesicles containing complex lipids and glycosaminoglycans (summary by Kawasaki et al., 2012).
A somatic dysfunction in which the pubic bones are pulled away from each other at the pubic symphysis. This dysfunction is frequently seen in women following childbirth.
A somatic dysfunction in which the innominate bone is rotated posteriorly around a transverse axis relative to the sacrum. The innominate moves more freely in posterior rotation and is restricted in anterior rotation. The anterior superior iliac spine (ASIS) is positioned superiorly and the posterior superior iliac spine (PSIS) is positioned inferiorly when compared to the contralateral landmarks.
A positional term based on the Strachan model referring to a sacral somatic dysfunction in which the sacral base has rotated posterior and sidebent to the side opposite to the rotation. The dysfunction is named for the side on which the posterior rotation occurs. The tissue texture changes are found at the lower pole on the side of rotation.(Foundations). (The motion characteristics of L5 are not described.)
A sacral somatic dysfunction described as an inferior shear of one side of the sacrum resulting in a deep sacral sulcus and ipsilateral inferior-posterior inferolateral angle of the sacrum.
A somatic dysfunction in which one pubic bone is displaced superiorly with relation to its normal mate.
A somatic dysfunction of the innominate (os coxae) resulting in lateral positioning of the anterior superior iliac spine (ASIS). The innominate moves more freely in a lateral direction, and is restricted from movement in a medial direction.
A somatic dysfunction in which one pubic bone is displaced inferiorly with relation to its normal mate.
A somatic dysfunction of the innominate (os coxae) resulting in medial positioning of the anterior superior iliac spine (ASIS). The innominate moves more freely in a medial direction and is restricted from movement in a lateral direction.
A somatic dysfunction in which the anterior superior iliac spine (ASIS) is anterior and inferior to the contralateral landmark. The innominate (os coxae) moves more freely in an anterior and inferior direction, and is restricted from movement in a posterior and superior direction.
A somatic dysfunction in which the basisphenoid and basiocciput are held forced together significantly limiting SBS motion.
Any of a group of somatic dysfunctions involving primarily the interrelationship between the basilarportion of the sphenoid (basisphenoid) and the basilar portion of the occiput (basiocciput).The abbreaviation, SBS, is often used in reporting somatic dysfunctions in this area.
Peptides which stimulate INSULIN release from the PANCREATIC BETA CELLS following oral nutrient ingestion, or postprandially.
A painful low back condition characterized by hypertonicity of psoas musculature. The syndrome consists of a constellation of typically related signs and symptoms.
A positional term based on the Strachan model referring to sacral somatic dysfunction in which the sacral base has rotated anterior and sidebent to the side opposite the rotation. The upper limb of the SI (sacroiliac) joint has restricted motion and is named for the side on which forward rotation had occurred. Tissue texture changes are found at the deep sulcus. (The motion characteristics of L5 are not described.)
A somatic dysfunction in which the anterior superior iliac spine (ASIS) and posterior superior iliac spines (PSIS) are inferior to the contralateral landmarks. The innominate (os coxa) moves more freely in an inferior direction, and is restricted from movement in a superior direction.
Motion and/or positional asymmetry associated with elastic deformation of connective tissue (fascia, ligament, membrane).
Sense of resistance to light traction applied to the skin. Related to the degree of moisture and degree of sympathetic nervous system activity.
1. Somatic dysfunction usually characterized by a rib being held in a position of exhalation such that motion toward exhalation is more free and motion toward inhalation is restricted. Synonyms: inhalation rib restriction exhalation strain, depressed rib. 2. An anterior rib tender point in counterstrain. . Somatic dysfunction usually characterized by a rib being held in a position of exhalation such that motion toward exhalation is more free and motion toward inhalation is restricted; Synonyms: inhalation rib restriction, exhalation strain, depressed rib. 2. An anterior rib tender point in counterstrain.
Movement of the ribs during respiration such that with inhalation the lateral aspect of the rib moves cephalad resulting in an increase of transverse diameter of the thorax. This type of rib motion is predominantly found in lower ribs, increasing from the upper to the lower ribs.
1. A system of reflex points that present as predictable anterior and posterior fascial tissue texture abnormalities (plaque-like changes or stringiness of the involved tissues) assumed to be reflections of visceral dysfunction or pathology.2. Originally used by Frank Chapman, DO, and described by Charles Owens, DO.
A concentric contraction against resistance in which the angular change of joint motion is at the same rate and the counterforce is less than the patient force.
The precise physiologic point in which the proprioceptive information provided by the ligaments allows the body to equalize the stresses exerted on an articulation in all directions.
An arteriovenous malformation in the vein of Galen that is located at the base of the brain. The malformation may result in developmental delays, hydrocephalus, seizures, and congestive heart failure.
The limit of motion imposed by anatomic structure; the limit of passive motion.
Impaired or altered function of the thoracic region.
Leprosy, also called Hansen disease, is a disorder known since ancient times. It is caused by bacteria called Mycobacterium leprae and is contagious, which means that it can be passed from person to person. It is usually contracted by breathing airborne droplets from affected individuals' coughs and sneezes, or by coming into contact with their nasal fluids. However, it is not highly transmissible, and approximately 95 percent of individuals who are exposed to Mycobacterium leprae never develop leprosy. The infection can be contracted at any age, and signs and symptoms can take anywhere from several months to 20 years to appear.Leprosy affects the skin and the peripheral nerves, which connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat. Most affected individuals have areas of skin damage (cutaneous lesions) and problems with nerve function (peripheral neuropathy); however, the severity and extent of the problems vary widely. Leprosy occurs on a spectrum, in which the most severe form is called multibacillary or lepromatous, and the least severe form is called paucibacillary or tuberculoid. Patterns of signs and symptoms intermediate between these forms are sometimes called borderline forms.Multibacillary leprosy usually involves a large number of cutaneous lesions, including both surface damage and lumps under the skin (nodules). The moist tissues that line body openings such as the eyelids and the inside of the nose and mouth (mucous membranes) can also be affected, which can lead to vision loss, destruction of nasal tissue, or impaired speech. Some affected individuals have damage to internal organs and tissues. The nerve damage that occurs in multibacillary leprosy often results in a lack of sensation in the hands and feet. Repeated injuries that go unnoticed and untreated because of this lack of sensation can lead to reabsorption of affected fingers or toes by the body, resulting in the shortening or loss of these digits.Paucibacillary leprosy typically involves a small number of surface lesions on the skin. There is generally loss of sensation in these areas, but the other signs and symptoms that occur in multibacillary leprosy are less likely to develop in this form of the disorder.In any form of leprosy, episodes called reactions can occur, and can lead to further nerve damage. These episodes can include reversal reactions, which involve pain and swelling of the skin lesions and the nerves in the hands and feet. People with the more severe forms of leprosy can develop a type of reaction called erythema nodosum leprosum (ENL). These episodes involve fever and painful skin nodules. In addition, painful, swollen nerves can occur. ENL can also lead to inflammation of the joints, eyes, and the testicles in men.Leprosy has long been stigmatized because of its infectious nature and the disfigurement it can cause. This stigma can cause social and emotional problems for affected individuals. However, modern treatments can prevent leprosy from getting worse and spreading to other people. While the infection is curable, nerve and tissue damage that occurred before treatment is generally permanent.
A form of eccentric contraction designed to break adhesions using an operator-induced force to lengthen the muscle and in which, the counterforce is greater than the patient force.
Impaired or altered function of the hand.
Any somatic dysfunction resulting in abnormal ligamentous tension or strain.
Any of a group of somatic dysfunctions involving the sacrum. These may be the result of restriction of normal physiologic motion or trauma to the sacrum.
Posterior movement of the base of the sacrum in relation to the ilia.
A type of keratitis characterized by inflammation in pinpoint areas of the corneal epithelium.
Impaired or altered function of the elbow.
Impaired or altered function of the ligament.
Impaired or altered function of the knee.
A sacral somatic dysfunction in which the entire sacrum has moved posteriorly (backward) between the ilia. Posterior motion is freer, and anterior motion is restricted.
Impaired or altered function of the forearm.
A form of LEPROSY classified by the World Health Organization for the purpose of treatment, based on clinical manifestations and skin smear results. Patients with paucibacillary leprosy have fewer than six skin lesions with no causative agent MYCOBACTERIUM LEPRAE on any slit-skin smear testing. Paucibacillary leprosy encompasses indeterminate, borderline tuberculoid, and tuberculoid leprosy.
A sacral somatic dysfunction in which the entire sacrum has moved anteriorly (forward)between the ilia. Anterior motion is freer, and posterior motion is restricted.
Movement of the ribs during respiration such that with inhalation, the anterior aspect of the rib moves cephalad and causes an increase in the anteroposterior diameter of the thorax. This type of rib motion is found predominantly in the upper ribs, decreasing in motion from the upper to the lower ribs.
Localized visceral stimuli producing patterns of reflex response in segmentally related somatic structures.
1. A sacral somatic dysfunction that involves rotation of the sacrum about a middle transverse axis such that the sacral base has moved posteriorly relative to the pelvic bones. Backward movement of the sacral base is freer, forward movement is restricted and both sulci are shallow. 2. The reverse of bilateral sacral flexion.
A somatic dysfunction in which one pubic bone is displaced posteriorly with relation to its normal mate.
Any cranial somatic dysfunction resulting in abnormal dural membrane tension.
An objective quantification of lumbar lordosis typically determined by measuring the angle between the superior surface of the second lumbar vertebra and the inferior surface of the fifth lumbar vertebra; best measured from a standing lateral x-ray film.
Impaired or altered function of the arm.
The limit to motion; in defining barriers, the palpatory end-feel characteristics are useful.
A tissue texture abnormality characterised principally by a palpable sense of sponginess in the tissue, interpreted as resulting from congestion due to increased fluid content.
A somatic dysfunction in which the pubic bones are forced toward each other at the pubic symphysis. This dysfunction is characterized by tenderness to palpation over the pubic symphysis, lack of apparent asymmetry, but associated with restricted motion of the pelvic ring.
Movements used to potentiate, accentuate, or compensate for an impairment in a physiologic motion (e.g., the movements needed to move a paralyzed limb).
Anterior movement of sacral base in relation to the ilia.
The inability to close the eyelids during sleep.
With the patient in a standing or seated position, any deviation of the sacral base from the horizontal in a coronal plane. Generally, the rotation of the sacrum about an anterior-posterior axis.
Impaired or altered function of the lumbar region.
Perceived quality of motion as an anatomic or physiologic restrictive barrier is approached.
A tissue texture abnormality characterized by a cord-like feeling.
Localized somatic stimuli producing patterns of reflex response in segmentally related somatic structures.
A somatic dysfunction in which one pubic bone is displaced anteriorly with relation to its normal mate.
The ideal physiologic state of harmonious equilibrium in the tension of the dura mater of the brain and spinal cord.
A sphenobasilar synchondrosis somatic dysfunction where the sphenoid and occiput have rotated in the same direction around parallel vertical axes. Lateral strains of the SBS are named for the position of the basisphenoid, right or left.
Yellow-white inflammatory aggregates in the vitreous that are found in the midvitreous and inferior periphery.
Posterior movement of the sacral base around a transverse axis in relation to the ilia.
Disorders resulting from defective DNA REPAIR processes or the associated cellular responses to DNA DAMAGE.
Agents that affect ION PUMPS; ION CHANNELS; ABC TRANSPORTERS; and other MEMBRANE TRANSPORT PROTEINS.
Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.
Agents that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS which are concentrated in the thick ascending limb at the junction of the LOOP OF HENLE and KIDNEY TUBULES, DISTAL. They act as DIURETICS. Excess use is associated with HYPOKALEMIA and HYPERGLYCEMIA.
Andersen-Tawil syndrome (ATS) is characterized by a triad of: episodic flaccid muscle weakness (i.e., periodic paralysis); ventricular arrhythmias and prolonged QT interval; and anomalies including low-set ears, widely spaced eyes, small mandible, fifth-digit clinodactyly, syndactyly, short stature, and scoliosis. Affected individuals present in the first or second decade with either cardiac symptoms (palpitations and/or syncope) or weakness that occurs spontaneously following prolonged rest or following rest after exertion. Mild permanent weakness is common. Mild learning difficulties and a distinct neurocognitive phenotype (i.e., deficits in executive function and abstract reasoning) have been described.
A congenital condition characterized by hypoplasia, absence, or ectopic position of the thyroid gland. It is manifested with congenital hypoparathyroidism.
Agents that reduce the excretion of URINE, most notably the octapeptide VASOPRESSINS.
The appearance of carbonyl groups (such as aldehyde or ketone groups) in PROTEINS as the result of several oxidative modification reactions. It is a standard marker for OXIDATIVE STRESS. Carbonylated proteins tend to be more hydrophobic and resistant to proteolysis.
Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS.
Genetic diseases that are linked to mutant ALLELES on the Y CHROMOSOME in humans (Y CHROMOSOME, HUMAN) or the Y chromosome in other species. Included here are animal models of human Y-linked diseases.
Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.
Agents that affect the function of FIBRIN in BLOOD COAGULATION. They used as COAGULANTS for HEMORRHAGE or ANTICOAGULANTS for THROMBOSIS.
The GENETIC RECOMBINATION of the parts of two or more GENES, including an ONCOGENE as at least one of the fusion partners. Such gene fusions are often detected in neoplastic cells and are transcribed into ONCOGENE FUSION PROTEINS.
Infections by MESOMYCETOZOEA, general or unspecified.
Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.
A dolastatin-10 peptide derivative with potent antimitotic activity and potential antineoplastic activity as part of an antibody-drug conjugate (ADC). Monomethyl auristatin E (MMAE) binds to tubulin, blocks tubulin polymerization, and inhibits microtubule formation, which results in both disruption of mitotic spindle assembly and arrest of tumor cells in the M phase of the cell cycle. To minimize toxicity and maximize efficacy, MMAE is conjugated, via a cleavable peptide linker, to a monoclonal antibody that specifically targets a patient's tumor. The linker is stable in the extracellular milieu but is readily cleaved to release MMAE following binding and internalization of the ADC by the target cells.
Conditions in which the primary symptom is HEADACHE and the headache cannot be attributed to any known causes.
Conditions with HEADACHE symptom that can be attributed to a variety of causes including BRAIN VASCULAR DISORDERS; WOUNDS AND INJURIES; INFECTION; drug use or its withdrawal.
A headache disorder characterized by episodes of unilateral, short lasting pain and associated ipsilateral cranial autonomic symptoms.
Difficulty in walking from place to place.
A synthetic melatonin analogue with hypnotic and circadian rhythm-modulating activities. Ramelteon binds to and activates melatonin receptors 1 and 2 in the suprachiasmatic nucleus (SCN) of the brain, thereby promoting the onset of sleep. Unlike the nonbenzodiazepine sedative hypnotics zolpidem and zaleplon, this agent does not activate GABA receptors and, so, produces no GABA receptor-mediated anxiolytic, myorelaxant, and amnesic effects.
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism. [HPO:probinson]
Conditions in which the function of KIDNEYS deteriorates suddenly in a matter of days or even hours. It is characterized by the sudden drop in GLOMERULAR FILTRATION RATE.
An orally available, competitive, beta-amino acid-derived inhibitor of dipeptidyl peptidase 4 (DDP-4) with hypoglycemic activity. Sitagliptin may cause an increased risk in the development of pancreatitis.
An embolic particle composed of water-soluble, compressible, nonabsorbable microspheres composed of tris-acryl gelatin, with potential use for embolization. Upon administration, the tris-acryl gelatin microspheres (TAGM) serve as an embolic agent before surgery for highly vascularized areas, such as those seen in certain tumors, by penetrating into the blood vessel system and blocking blood flow. These microspheres may be used to encapsulate various therapeutic agents; drug-loaded microspheres can then be used as drug delivery vehicles during embolization of tumor vasculature.
A thiazolidinedione derivative with antihyperglycemic activity. Balaglitazone exerts partial peroxisome proliferator-activated receptor (PPAR) gamma agonistic activity and appears to be associated with fewer side effects as compared to full PPAR gamma agonists.
A recombinant humanized monoclonal antibody fragment that binds VEGF-A to prevent its binding to VEGFR-1 and VEGFR-2 receptors. This activity reduces vessel permeability and angiogenesis in the treatment of neovascular age-related MACULAR DEGENERATION.
The need for dialysis within a week of kidney transplant.
The mesylate salt form of pradefovir, a cyclodiester antiviral prodrug with specific activity against hepatitis B virus (HBV). Pradefovir is specifically metabolized in the liver by hepatic enzymes, mainly by CYP4503A4, to adefovir. In turn, adefovir is phosphorylated by cellular kinases to its activated form adevofir diphosphate. By competing with the natural substrate dATP, the diphosphate form is incorporated into viral DNA and inhibits RNA-dependent DNA polymerase. This causes DNA chain termination and eventually results in an inhibition of HBV replication.
A diarylpyrimidine derivative and REVERSE TRANSCRIPTASE INHIBITOR with antiviral activity against HIV-1 that is used in the treatment of HIV INFECTIONS. It is also used in combination with other ANTI-HIV AGENTS, since ANTIVIRAL DRUG RESISTANCE emerges rapidly when it is used alone.
An inhibitor of the protein tyrosine phosphatase 1B (PTP1B) and dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist with hypoglycemic and anti-lipidemic activity. Ertiprotafib inhibits PTP1B preventing the dephosphorylation of the insulin receptor, which improves insulin sensitivity and decreases blood glucose levels. In addition, this agent is able to stimulate both PPAR alpha and gamma thereby further improving glucose homeostasis and reducing triglyceride (TG) and free fatty acid levels. Ertiprotafib was also shown to be a potent inhibitor of IkappaB kinase beta (IKKbeta), which cotributes to its anti-inflammatory properties.
A second-generation synthetic antisense oligonucleotide with potential antineoplastic activity. AEG35156 selectively blocks the cellular expression of X-linked inhibitor of apoptosis protein (XIAP), a pivotal inhibitor of apoptosis that is overexpressed in many tumors. This agent reduces total levels of XIAP in tumor cells, working synergistically with cytotoxic drugs to overcome tumor cell resistance to apoptosis. XIAP interferes with both the intrinsic and extrinsic program-death signaling pathways, which may render tumor cells resistant to apoptosis.
A CD22-targeted cytotoxic immunoconjugate composed of a humanized IgG4 anti-CD22 antibody covalently linked to N-acetyl-gamma-calicheamicin dimethyl hydrazide (CalichDMH) with potential antineoplastic activity. Inotuzumab ozogamicin is rapidly internalized upon binding of the antibody moiety to B cell-specific CD22 receptors, delivering the conjugated CalichDMH intracellularly; the CalichDMH moiety binds to the minor groove of DNA in a sequence-specific manner, resulting in double-strand DNA breaks and apoptosis. CalichDMH is a derivative of gamma calicheamicin, a cytotoxic antibiotic produced by the bacterium Micromonospora echinospora.
Unilateral multicystic dysplastic kidney is the form of multicystic dysplastic kidney (MCDK, see this term), a congenital anomaly of the kidney and urinary tract (CAKUT), in which one kidney is large, distended by multiple cysts, and non-functional.
Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities.People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as this condition progresses, resulting in end-stage renal disease (ESRD).People with Alport syndrome frequently develop sensorineural hearing loss, which is caused by abnormalities of the inner ear, during late childhood or early adolescence. Affected individuals may also have misshapen lenses in the eyes (anterior lenticonus) and abnormal coloration of the light-sensitive tissue at the back of the eye (retina). These eye abnormalities seldom lead to vision loss.Significant hearing loss, eye abnormalities, and progressive kidney disease are more common in males with Alport syndrome than in affected females.
In Alport syndrome (AS) a spectrum of phenotypes ranging from progressive renal disease with extrarenal abnormalities to isolated hematuria with a non-progressive or very slowly progressive course is observed. Approximately two thirds of AS is X-linked (XLAS); approximately 15% is autosomal recessive (ARAS), and approximately 20% is autosomal dominant (ADAS). In the absence of treatment, renal disease progresses from microscopic hematuria (microhematuria) to proteinuria, progressive renal insufficiency, and end-stage renal disease (ESRD) in all males with XLAS, and in all males and females with ARAS. Progressive sensorineural hearing loss (SNHL) is usually present by late childhood or early adolescence. Ocular findings include anterior lenticonus (which is virtually pathognomonic), maculopathy (whitish or yellowish flecks or granulations in the perimacular region), corneal endothelial vesicles (posterior polymorphous dystrophy), and recurrent corneal erosion. In individuals with ADAS, ESRD is frequently delayed until later adulthood, SNHL is relatively late in onset, and ocular involvement is rare.
An orally active, synthetic retinoid, developed to overcome all-trans retinoic acid (ATRA) resistance, with potential antineoplastic activity. As a specific retinoic acid receptor (RAR) alpha/beta agonist, tamibarotene is approximately ten times more potent than ATRA in inducing cell differentiation and apoptosis in HL-60 (human promyelocytic leukemia) cell lines in vitro. Due to a lower affinity for cellular retinoic acid binding protein (CRABP), tamibarotene may show sustained plasma levels compared to ATRA. In addition, this agent may exhibit a lower toxicity profile than ATRA, in part, due to the lack of affinity for the RAR-gamma receptor, the major retinoic acid receptor in the dermal epithelium.
A purine nucleotide analog prodrug with activity against wild-type and lamivudine-resistant hepatitis B virus (HBV). Alamifovir acts by inhibiting viral DNA priming and viral DNA packaging, thereby decreasing HBV replication.
A C-C Chemokine Receptor Type 5 (CCR5) antagonist with activity against HIV-1. Aplaviroc inhibits HIV-1 entry via CCR5 coreceptor interaction.
Derivatives of TRYPTAMINES that are SEROTONIN RECEPTOR AGONISTS acting at 5-HT1 RECEPTORS. Some are used to treat MIGRAINE DISORDERS.
An injectable microemulsion of a purified oil extracted from the seeds of the traditional Chinese medicinal herb Coix lacryma-jobi (Job's tears), with potential antineoplastic activity. Although the exact mechanism of action is unknown, kanglaite exhibits an antineoplastic effect, potentially via interfering with the cell cycle and halting tumor cells in the G2/M phase, which may eventually inhibit mitosis and proliferation of cancer cells.
Usher syndrome type I is characterized by congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa. Unless fitted with a cochlear implant, individuals do not typically develop speech. Retinitis pigmentosa (RP), a progressive, bilateral, symmetric degeneration of rod and cone functions of the retina, develops in adolescence, resulting in progressively constricted visual fields and impaired visual acuity.
Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995). For a discussion of phenotypic heterogeneity of Usher syndrome, see USH1 (276900). Genetic Heterogeneity of Usher syndrome Type III Usher syndrome type IIIB (614504) is caused by mutation in the HARS gene (142810) on chromosome 5q31.3.
Clinical syndrome describing overuse tendon injuries characterized by a combination of PAIN, diffuse or localized swelling, and impaired performance.
Chronic degeneration of tendon without inflammation.
An orally active, 1,2-benzisoxazole-containing, inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Razaxaban forms an isoxazole-ring opened, stable, benzamidine metabolite which is subsequently excreted through the bile.
A dual peroxisome proliferator-activated receptor (PPAR) agonist, with hypoglycemic activity. Muraglitazar causes an increase in HDL-C levels, and a decrease in total cholesterol, apolipoprotein B, triglycerides and HbA1c. This agent is associated with an increased risk of adverse cardiovascular events and heart failure.
An orally available pyridopyrimidine-derived cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. PD-0332991 selectively inhibits cyclin-dependent kinases (particularly Cdk4/cyclin D1 kinase), which may inhibit retinoblastoma (Rb) protein phosphorylation; inhibition of Rb phosphorylation prevents Rb-positive tumor cells from entering the S phase of the cell cycle (arrest in the G1 phase), resulting in suppression of DNA replication and decreased tumor cell proliferation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=454586&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=454586&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C49176"" NCI Thesaurus)
An orally bioavailable small-molecule androgen receptor modulator and CYP17 lyase inhibitor with potential antiandrogen activity. Galeterone exhibits three distinct mechanisms of action: 1) as an androgen receptor antagonist, 2) as a CYP17 lyase inhibitor and 3) by decreasing overall androgen receptor levels in prostate cancer tumors, all of which may result in a decrease in androgen-dependent growth signaling. Localized to the endoplasmic reticulum (ER), the cytochrome P450 enzyme CYP17 (P450C17 or CYP17A1) exhibits both 17alpha-hydroxylase and 17,20-lyase activities, and plays a key role in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.
A benzazepine derivative that functions as an ALPHA4-BETA2 NICOTINIC RECEPTOR partial agonist. It is used for SMOKING CESSATION.
An iodine 131 (I 131) radioconjugate of the synthetic chlorotoxin (CTX) TM-601 with potential antiangiogenic and antineoplastic activities. CTX is a 36 amino acid neurotoxin found in the venom of the giant yellow scorpion Leiurus quinquestriatus that preferentially binds malignant cells of neuroectodermal origin. The recombinant version of this peptide, TM-601, is expressed in and purified from E. coli and then covalently linked to I 131 to produce 131I-TM-601. 131I-TM-601 binds to tumor cells of neuroectodermal origin and is internalized; administered once, it may be used as a radioimaging agent; repeated administration may result in a tumor-specific, cumulative radiocytotoxic dose of I 131. In addition, TM-601 alone, similar to native CTX, may inhibit angiogenesis due to its ability to bind to and inhibit matrix metalloproteinase 2 (MMP-2), an endopeptidase involved in tissue remodeling processes such as angiogenesis.
Insulin-like growth factor II (180 aa, ~20 kDa) is encoded by the human IGF2 gene. This protein plays a role in cellular growth, development, and mitogenesis.
An orally bioavailable, selective small molecule B-cell lymphoma 2 (Bcl-2) Homology 3 (BH3) mimetic, with potential pro-apoptotic and antineoplastic activities. ABT-737 binds to the hydrophobic groove of multiple members of the anti-apoptotic Bcl-2 protein family, including Bcl-2, Bcl-xl and Bcl-w. This inhibits the activity of these pro-survival proteins and restores apoptotic processes in tumor cells, via activation of Bak/Bax-mediated apoptosis. The pro-survival Bcl-2 proteins are overexpressed in many cancers and play important roles in the regulation of apoptosis. Their expression is associated with increased drug resistance and tumor cell survival. ABT-737 does not inhibit the pro-survival proteins Mcl-1, Bcl-B, Bfl-1 (A1); therefore, tumors that overexpress these Bcl-2 family proteins are resistant to ABT-737.
A dual peroxisome proliferator-activated receptor (PPAR) agonist, with hypoglycemic activity. Tesaglitazar is more potent on the gamma subtype than on the alpha subtype of PPAR. This agent improves atherogenic dyslipidemia but may cause an increase in fibrosarcoma formation.
A humanized monoclonal antibody directed against the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Nimotuzumab binds to and inhibits EGFR, resulting in growth inhibition of tumor cells that overexpress EGFR. This agent may act synergistically with radiation therapy.
The hydrochloride salt form of 2-amino-2 propanediol (KRP-203), a sphingosine 1-phosphate (S1P) receptor agonist, with potential immunosuppressive activity. Upon administration of S1P receptor agonist KRP203, this agent binds to S1P receptors on lymphocytes, which prevents binding of serum S1P to S1P receptors and leads to S1P receptor internalization. This reduces the number of circulating blood leukocytes and accelerates lymphocyte homing into peripheral lymph nodes, thereby preventing their infiltration into peripheral inflammatory sites. This agent also decreases the production of inflammatory cytokines by lymphocytes, such as interferon gamma (IFN-g), interleukin-12 (IL-12), and tumor necrosis factor (TNF).
A cyanopyrrolidine-based, orally bioavailable inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Vildagliptin's cyano moiety undergoes hydrolysis and this inactive metabolite is excreted mainly via the urine.
Interacting selectively and non-covalently with tetrahydrodictyopterin, the pterin 2-amino-6-[(1R,2R)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydropteridin-4(3H)-one. [CHEBI:52447, GOC:mah, GOC:vw]
Severe mental disorder with onset in MIDDLE AGE, marked by withdrawal, abnormal affect, disturbed intellectual processes, and there may be regression.
A mouse monoclonal antibody directed against human cluster of differentiation 15 (CD15 or 3-fucosyl-N-acetyllactosamine). Fanolesomab binds to CD15; radioactive labeled fanolesomab may facilitate the visualization of infection sites upon imaging. The CD15 antigen, a carbohydrate adhesion molecule, is expressed on the surface of the majority of granulocytes, including neutrophils and eosinophils and, to a lesser extent, on monocytes. Due to life-threatening side effects, this antibody is no longer on the market.
The sodium salt form of pegaptanib, a 28-mer RNA aptamer covalently linked to two branched 20-kD polyethylene glycol (PEG) chains, with anti-angiogenic activity. Pegaptanib binds and blocks the activity of the extracellular vascular endothelial growth factor, specifically the 165-amino acid isoform (VEGF165). This prevents VEGF165 from binding to VEGF receptors, thereby blocking angiogenesis as well as preventing VEGF165-induced increases in vessel permeability. VEGF165 is preferentially involved in pathological ocular neovascularisation.
The tartrate salt form of levalbuterol, the R-enantiomer of the short-acting beta-2 adrenergic receptor agonist albuterol, with bronchodilator activity. Levalbuterol selectively binds to beta-2 adrenergic receptors in bronchial smooth muscle, thereby activating intracellular adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels cause relaxation of bronchial smooth muscle, relieve bronchospasms, improve mucociliary clearance and inhibit the release of mediators of immediate hypersensitivity from cells, especially from mast cells.
A highly purified preparation of ovine testicular hyaluronidase with potential chemoadjuvant activity. Upon subcutaneous administration, hyaluronidase modifies the permeability of connective tissue by hydrolyzing hyaluronic acid. This temporarily decreases interstitial viscosity and allows drugs that are co-injected to spread rapidly through the interstitial space, thereby facilitating absorption and/or distribution of co-injected agents.
An outward deviation of the foot at the talocalcaneal or subtalar joint.
Sexual intercourse without the use of precautions to prevent conception or the transmission of sexually transmitted diseases.
Insulinomatosis and diabetes mellitus syndrome is an autosomal dominant disorder in which affected individuals within a family present with either hyperinsulinemic hypoglycemia secondary to pancreatic neuroendocrine tumors, or a noninsulin-dependent form of diabetes mellitus. A few affected individuals show only impaired glucose tolerance. Some patients also exhibit congenital cataract and/or congenital glaucoma (Iacovazzo et al., 2018).
A class of agents that act by selectively inhibiting aldosterone receptor activation with diuretic activity. Aldosterone receptor antagonists bind to and block the activation of aldosterone (mineralocorticoid) receptors on the epithelial cells in the late distal tubule and collecting duct of the kidney, thus preventing the synthesis of aldosterone-induced proteins which enhance Na+ retention and K+ and H+ secretion. The enhanced excretion of Na+ produces diuresis ultimately resulting in a reduction in blood pressure without the loss of K+.
A vaccine containing detoxified tetanus toxoid, detoxified diphtheria toxoid and acellular pertussis antigens, adsorbed on aluminum phosphate, with active immunizing activity against diphtheria, tetanus and pertussis. The acellular pertussis vaccine components, produced by Bordetella pertussis, are detoxified pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and fimbriae types 2 and 3 (FIM). Intramuscular injection with this vaccine activates the immune system to develop antibodies against tetanus toxin, diphtheria toxin and B. pertussis antigens.
An active immunizing vaccine used to prevent infection by the bacterium Streptococcus pneumoniae. It consists of a solution of saccharides of the capsular antigens of Streptococcus serotypes individually conjugated to proteins.
Drugs that selectively block or suppress the plasma membrane transport of SEROTONIN and NORADRENALINE into axon terminals and are used as ANTIDEPRESSIVE AGENTS.
The monohydrate bromide salt form of tiotropium, a quaternary ammonium derivative of atropine and a long-acting muscarinic receptor antagonist, with bronchodilating activity. Upon inhalation, tiotropium binds to and blocks mainly muscarinic M3 receptors located on smooth muscle cells, thereby preventing smooth muscle contraction.
synthetic or natural chemical compound resembling nucleosides in structure and/or function.
A thiophene-containing local anesthetic pharmacologically similar to MEPIVACAINE.
A rare syndrome characterized by the presence of an enlarged and weak bladder (megacystis), a very small large intestine (microcolon), and weak small intestine that does not function properly (hypoperistalsis). It is caused by a disorder of the smooth muscles of the abdomen and gastrointestinal tract.
A head tremor of moderate speed (3 to 4 Hz) in the anterior-posterior direction.
Description:The medication is being re-prescribed at a different dosage.
A humanized monoclonal antibody that binds to IL-12 and IL-23 and is used as a DERMATOLOGIC AGENT in the treatment of patients with plaque PSORIASIS who have not responded to other therapies.
Leakage of a pharmacologic or a biological substance from the infusion site into the surrounding tissue. Signs and symptoms include induration, erythema, swelling, burning sensation, and pain at the infusion site.
A recombinant, humanized IgG1 monoclonal antibody directed against the interleukin-6 receptor (IL-6R) with immunosuppressant activity. Tocilizumab targets and binds to both the soluble form of IL-6R (sIL-6R) and the membrane-bound form (mIL-6R), thereby blocking the binding of IL-6 to its receptor. This prevents IL-6-mediated signaling. Il-6, a pro-inflammatory cytokine that plays an important role in the regulation of the immune response, is overproduced in autoimmune disorders and certain types of cancers.
A bilateral form of agenesis of the kidney.
FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent.
A fungal infection by any of the Candida species in a sterile body compartment.
The asymptomatic presence of Mycobacterium tuberculosis in the body, which is determined by a positive result to a tuberculin skin test or interferon-gamma release assay.
An orally available small molecule and cyclin-dependent kinase (CDK) inhibitor with potential apoptotic and antineoplastic activity. CDKs, serine/threonine kinases that play an important role in cell cycle regulation, are overexpressed in various malignancies. Seliciclib primarily inhibits CDK 2, 7, and 9 by competing for the ATP binding sites on these kinases, leading to a disruption of cell cycle progression. In addition, this agent seems to interfere with CDK-mediated phosphorylation of the carboxy-terminal domain of RNA polymerase II, thereby inhibiting RNA polymerase II-dependent transcription. This may lead to the down-regulation of anti-apoptotic factors, such as myeloid cell leukemia sequence 1 (Mcl-1), a protein crucial for the survival of a range of tumor cell types. The down-regulation of anti-apoptotic factors may lead to an induction of apoptosis, thereby further contributing to seliciclib's antiproliferative effects.
A chimeric, human-murine, monoclonal antibody targeting the pro-inflammatory cytokine interleukin 6 (IL-6), with antitumor and anti-inflammatory activities. Upon intravenous administration of siltuximab, this agent targets and binds to IL-6. This inhibits the binding of IL-6 to the IL-6 receptor (IL-6R), which results in the blockade of the IL-6/IL-6R-mediated signal transduction pathway. This inhibits cancer cell growth in tumors overexpressing IL-6.
Congenital anomaly characterized by closure or failure to develop an opening in the urethra.
A long-acting salicylate derivative with antilipidemic properties. Hydroxytoluic acid has been shown to lower plasma free fatty acid and cholesterol levels.
A third generation, synthetic, water-soluble, pentapeptide analog of the marine depsipeptide dolastatin 15, with potential antimitotic and antineoplastic activities. Tasidotin and its metabolite, tasidotin C-carboxylate, suppress the dynamic instability behavior of the microtubules through a reduction of the shortening rate (disassembly); reduction of the switching frequency from growth to shortening; and by reducing microtubules growth time. This may eventually result in a reduction of cell growth.
A cystatin subtype that has a diverse tissue distribution, target specificity, and functions as an endogenous inhibitor of lysosomal cysteine proteases.
Nail whose growth pattern or speed deviates from normal.
A complication of INTERNAL MAMMARY-CORONARY ARTERY ANASTOMOSIS whereby an occlusion or stenosis of the proximal SUBCLAVIAN ARTERY causes a reversal of the blood flow away from the CORONARY CIRCULATION, through the grafted INTERNAL MAMMARY ARTERY (internal thoracic artery), and back to the distal subclavian distribution.
An infectious process affecting a surgically created opening in the surface of the body.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in a coronary artery.
A rare genetic non-dystrophic myopathy characterised by early diffuse, progressive muscle and joint contractures that result in severe limitation of movement of axial, proximal and distal joints, walking difficulties in early childhood and toe walking. Patients typically present thin, sclerotic muscles with a woody consistency, mild girdle and proximal limb weakness with moderate distal weakness and scoliosis. Muscle biopsy shows partial collagen VI deficiency at the myofibre basement membrane and absent collagen VI around most endomysial/perimysial capillaries. There is evidence the disease is caused by homozygous mutation in the COL6A2 gene.
A pathologic finding indicating the presence of leukemic cell infiltrates in the brain tissue.
A potent, selective and competitive, cyanopyrrolidine-based, orally bioavailable inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Saxagliptin is metabolized into an, although less potent, active mono-hydroxy metabolite.
A liposomal small-molecule glutathione analog inhibitor of glutathione S-transferase (GST) P1-1 with hematopoiesis-stimulating activity. After intracellular de-esterification, the active form of TLK199 (TLK117) binds to and inhibits GST P1-1, thereby restoring Jun kinase and MAPK pathway activities and promoting MAPK-mediated cellular proliferation and differentiation pathways. This agent promotes the proliferation and maturation of hematopoietic precursor cells, granulocytes, monocytes, erythrocytes and platelets. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=485244&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=485244&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61326"" NCI Thesaurus)
A nutritional supplement composed of an aqueous extract derived from the leaves of the tropical fern belonging to the Polypodiaceae family, Polypodium leucotomos (PL; Phlebodium aureum), with potential photoprotective, skin protective, anti-inflammatory, immunomodulating and antioxidant activities. This extract contains many phenolic compounds, such as ferulic, caffeic, coumaric and vanillic acid, which are mainly responsible for this extract's effects. Upon administration, Polypodium leucotomos extract (PLE) exerts antioxidant activity by scavenging free radicals and inhibiting the generation and release of reactive oxygen species (ROS), thereby preventing ultraviolet (UV)-induced as well as ROS-induced DNA damage. In addition, the chemicals in this extract protect antioxidant enzymes and modulate expression of cancer and inflammation-related genes, including the induction of the expression of tumor suppressor genes and the inhibition of the expression of pro-inflammatory cytokines and inflammatory enzymes, thereby inhibiting the activation of signal transduction pathways involved in carcinogenesis and inflammation, respectively. PLE also stimulates tissue inhibitors of metalloproteinases (TIMPs) and inhibits matrix metalloproteinases (MMPs).
A selective thiophene-derived tyrosine kinase inhibitor with potential antineoplastic activity. Tyrosine kinase inhibitor OSI-930 inhibits stem cell factor receptor (c-Kit) and the vascular endothelial growth factor receptor 2 (VEGFR2), which may result in the inhibition of both tumor cell proliferation and tumor angiogenesis. Both c-Kit and VEGFR2 are overexpressed in a variety of cancers.
A synthetic, orally bioavailable, achiral, tridentate triazole derived from salicylic acid with iron-chelating activity. Deferasirox chelates iron at a 2:1 (ligand:iron) ratio. Because of its oral availability and long plasma half-life, this agent may be superior to desferrioxamine (desferal, DFO), which is orally inactive and has a short plasma half-life.
A chronic, acquired, idiopathic, progressive eruption of the skin that occurs in the context of RENAL FAILURE. It is sometimes accompanied by systemic fibrosis. The pathogenesis seems to be multifactorial, with postulated involvement of circulating fibrocytes. There is a strong association between this disorder and the use of gadolinium-based contrast agents.
Renal hypodysplasia/aplasia belongs to a group of perinatally lethal renal diseases, including bilateral renal aplasia, unilateral renal agenesis with contralateral dysplasia (URA/RD), and severe obstructive uropathy. Renal aplasia falls at the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT; 610805), and usually results in death in utero or in the perinatal period. Families have been documented in which bilateral renal agenesis or aplasia coexists with unilateral renal aplasia, renal dysplasia, or renal aplasia with renal dysplasia, suggesting that these conditions may belong to a pathogenic continuum or phenotypic spectrum (summary by Joss et al., 2003; Humbert et al., 2014). Genetic Heterogeneity of Renal Hypodysplasia/Aplasia RHDA2 (615721) is caused by mutation in the FGF20 gene (605558) on chromosome 8p22, and RHDA3 (617805) is caused by mutation in the GREB1L gene (617782) on chromosome 18q11.
An infectious disorder caused by the use of a medical device.
Telangiectasia affecting thegastrointestinal tract.
Pain associated with examination, treatment or procedures.
Exuberant inflammatory response towards a previously acquired or undiagnosed opportunistic infection. It is frequently seen in AIDS patients following antiretroviral treatment.
A fusion protein immunoconjugate of the extracellular domain of CTLA4 and the Fc domain of human IgG1. It functions as a T-cell co-stimulation blocker that inhibits TNF-ALPHA and prevents the activation of T-LYMPHOCYTES. It is used in the treatment of RHEUMATOID ARTHRITIS.
A novel platelet inhibitor approved for the reduction of thrombotic cardiovascular events in patients with acute coronary syndrome. Prasugrel produces inhibition of platelet aggregation by binding to receptors for ADP on the surface of platelets.
A formulated therapeutic analog of the endogenous alpha interferon containing multiple interferon species with antiviral and antitumor properties. Interferons bind to specific cell-surface receptors, leading to the transcription and translation of genes with an interferon-specific response element, thereby inducing: antiviral effects (the most important being inhibition of viral protein synthesis); antiproliferative effects (including inhibition of cellular growth and alteration of cellular differentiation); anticancer effects (including interference with oncogene expression); and immune-modulating effects (including activation of natural killer cells, alteration of cell surface antigen expression, and augmentation of lymphocyte and macrophage cytotoxicity). (NCI04)
Compounds that bind to and inhibit the action of ADENYLYL CYCLASES.
A protein that plays a role in the regulation of ubiquitination of other proteins and, subsequently, modulates the targeting of proteins for degradation by the proteasome.
A variant of peripheral T-cell lymphoma, not otherwise specified. It is characterized by the presence of neoplastic small lymphocytes infiltrating the lymph nodes in a diffuse and less frequently interfollicular pattern. There is an associated proliferation of epithelioid histiocytes forming confluent clusters.
A mental state of reduced level of consciousness, with decreased response to stimuli, including pain.
A congenital or acquired hyperplasia of the cells of the adrenal cortex or medulla.
A tumor arising from glia in the central nervous system with macroscopic regions of necrosis and hemorrhage. Microscopically, glioblastoma multiforme is characterized by regions of pseudopalisading necrosis, pleomorphic nuclei and cells, and microvascular proliferation.
A water-soluble prodrug of ceftobiprole, a pyrrolidinone cephalosporin antibiotic, with bactericidal activity. Ceftobiprole binds to and inactivates penicillin-binding proteins (PBPs), enzymes involved in the terminal stages of bacterial cell wall assembly and cell wall reshaping during bacterial growth and division. This agent exhibits a broad spectrum of activity against gram-negative and gram-positive pathogens including methicillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA). Ceftobiprole is refractory to hydrolysis by class A and class C lactamases.
The Finnish type of systemic amyloidosis is characterized clinically by a unique constellation of features including corneal lattice dystrophy, and cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure. The disorder is usually inherited in an autosomal dominant pattern; however, homozygotes with a more severe phenotype have also been reported (Meretoja, 1973).
Exaggerated curvature of the lens of the eye, producing an anterior or posterior spherical bulging.
A nutritional cirrhosis that is characterized by increase connective tissue surrounding the portal spaces.
A benign brain tumor composed of neural elements which most often arise from the SEPTUM PELLUCIDUM and the walls of the lateral ventricles. Immunohistochemistry and electron microscopy evaluations may reveal expression of neuron specific enolase and synaptophysin and cells containing microtubuli, neurosecretory granules, and presynaptic vesicles. (From Acta Med Port 1994 Feb;7(2):113-9)
An antiquated term for a diffuse B-or T-cell lymphoma composed of small cleaved lymphocytes, occurring in adults.
Specific degradation of a protein - involving conjugation, transport, oxidation, and proteolysis - involved in signal transduction or cell communication events; not to be confuse with proteolysis, which applies only to peptide bond hydrolysis. (NCI)
SALL4-related disorders include Duane-radial ray syndrome (DRRS, Okihiro syndrome), acro-renal-ocular syndrome (AROS), and SALL4-related Holt-Oram syndrome (HOS), three phenotypes previously thought to be distinct entities: DRRS is characterized by uni- or bilateral Duane anomaly and radial ray malformation that can include thenar hypoplasia and/or hypoplasia or aplasia of the thumbs, hypoplasia or aplasia of the radii, shortening and radial deviation of the forearms, triphalangeal thumbs, and duplication of the thumb (preaxial polydactyly). AROS is characterized by radial ray malformations, renal abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, vesico-ureteral reflux, bladder diverticula), ocular coloboma, and Duane anomaly. Rarely, pathogenic variants in SALL4 may cause clinically typical HOS (i.e., radial ray malformations and cardiac malformations without additional features).
A rare variant of mycosis fungoides, characterized by cerebriform lymphocytic infiltration of the hair follicles of the head and neck. Most cases show mucinous degeneration of the hair follicles, and are designated as mycosis fungoides-associated follicular mucinosis. Cases without mucinous degeneration have been reported as pilotropic mycosis fungoides. There is no difference in clinical presentation or outcome between mycosis fungoides-associated follicular mucinosis and pilotropic mycosis fungoides. In the recent WHO-EORTC classification, folliculotropic mycosis fungoides is the preferred term for all cases.
A palpable change in tissues from skin to periarticular structures that represents any combination of the following signs: vasodilation, edema, flaccidity, hypertonicity, contracture, fibrosis, as well as the following symptoms: itching, pain, tenderness, paresthesias. Types of TTA's include: bogginess, thickening, stringiness, ropiness, firmness (hardening), increased/decreased temperature and/or increased/decreased moisture.
Pelvic rotation about a transverse (horizontal) axis (forward or backward tilt) or about an anterior-posterior axis (right or left side tilt).
The age at which permanent cessation of menses occurs.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by episodic syncope occurring during exercise or acute emotion in individuals without structural cardiac abnormalities. The underlying cause of these episodes is the onset of fast ventricular tachycardia (bidirectional or polymorphic). Spontaneous recovery may occur when these arrhythmias self-terminate. In other instances, ventricular tachycardia may degenerate into ventricular fibrillation and cause sudden death if cardiopulmonary resuscitation is not readily available. The mean age of onset of symptoms (usually a syncopal episode) is between age seven and twelve years; onset as late as the fourth decade of life has been reported. If untreated, CPVT is highly lethal, as approximately 30% of affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. Sudden death may be the first manifestation of the disease.
Macular corneal dystrophy (MCD) is an autosomal recessive disorder in which progressive punctate opacities in the cornea result in bilateral loss of vision, eventually necessitating corneal transplantation. MCD is classified into 2 subtypes, type I and type II, defined by the respective absence and presence of sulfated keratan sulfate in the patient serum, although both types have clinically indistinguishable phenotypes (summary by Akama et al., 2000).
An allergic reaction to an allergen substance derived from a non-food plant, rather than a reaction to the plant organism itself.
While performing an assessment of the eyes, the examiner notes whether the pupils are equal, round, and reactive to light. If all findings are normal, the abbreviation PERRL is noted in the examiner's account of the physical examination.
The spectrum of ADAMTSL4-related eye disorders is a continuum that includes the phenotypes known as ""autosomal recessive isolated ectopia lentis"" and ""ectopia lentis et pupillae"" as well as more minor eye anomalies with no displacement of the pupil and very mild displacement of the lens. Typical eye findings are dislocation of the lens, congenital abnormalities of the iris, refractive errors that may lead to amblyopia, and early-onset cataract. Increased intraocular pressure and retinal detachment may occur on occasion. Eye findings can vary within a family and between the eyes in an individual. In general, no additional systemic manifestations are observed, although skeletal features have been reported in a few affected individuals.
An allergy to a substance derived from an adhesive bandage rather than the physical bandage itself.
A racemic mixture of alanine, a non-essential alpha-amino acid. Alanine is one of the most common residues for protein synthesis and is involved in the metabolism of tryptophan and vitamin pyridoxine. Furthermore, alanine is an important source of energy for muscles and central nervous system. It strengthens the immune system, helps in the metabolism of sugars and organic acids, and displays a cholesterol-reducing effect in animals.
The presence of mildly increased concentrations of albumin in the urine (in adults, 30-150 mg per day).
Trapping and compression of the rotator cuff tendons during shoulder movements.
A drug implant that acts as a birth control device and which is inserted under the skin for drug delivery into the body.
A synthetic human therapeutic agent which is chemically identical or similar to endogenous secretin, a peptide hormone found in the mucosal S-cells of the proximal small intestine. Secretin stimulates the pancreatic acinar cells and ductal epithelial cells to emit bicarbonate rich digestive fluids, thereby increases duodenal bicarbonate level. Bicarbonate neutralizes acidity of the intestines, consequently increasing the pH and facilitating the action of intestinal digestive enzymes. In addition, secretin stimulates the stomach and the liver to produce pepsin and bile, respectively. Both pepsin and bile aide the digestive action of the duodenum, which resulting in the prevention of gastric inflammation.
Measurement of relative composition of different BREAST tissue types often determined from MAMMOGRAPHY; ULTRASONOGRAPHY; or MRI.
A sensation of tightness in a toe joint when attempting to move it, especially after a period of inactivity.
The 3-O-valine ester prodrug of the nucleoside analog 2'-C-methylcytidine with anti-hepatitis C virus (HCV) activity. Upon administration, valopicitabine is converted into 2'-C-methylcytidine; upon phosphorylation into its 5-triphosphate form, this metabolite inhibits viral RNA chain elongation and viral RNA-dependent RNA polymerase activity. This blocks viral production of HCV RNA and thus viral replication.
A diarylquinoline antibiotic that works by inhibiting mycobacterial ATP synthase. TMC207 enhances the antibacterial activity of second-line drug combinations.
A fully human agonistic monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor-1 (TRAIL-R1) with apoptosis promoting and potential antitumor activities. TRAIL-R1 is a cell surface receptor expressed on many malignant cell types. Mapatumumab selectively binds to and activates the TRAIL cell receptor, thereby inducing apoptosis and reducing tumor growth.
A C-C Chemokine Receptor Type 5 (CCR5) antagonist with activity against human immunodeficiency virus (HIV). Maraviroc inhibits HIV-1 entry via CCR5 coreceptor interaction.
A pyrazine-derived DIPEPTIDYL-PEPTIDASE IV INHIBITOR and HYPOGLYCEMIC AGENT that increases the levels of the INCRETIN hormones GLUCAGON-LIKE PEPTIDE-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). It is used in the treatment of TYPE 2 DIABETES.
A quinacrine mustard compound with potential antineoplastic activity. Amustaline binds to, intercalates and crosslinks DNA and RNA. This agent is mainly used for ex vivo purposes, specifically for the inactivation of pathogens such as viruses, protozoa and bacteria in red blood cells (RBCs).
A cyclopentane derivative with activity against influenza A and B viruses. Peramivir is a neuraminidase inhibitor which prevents normal processing of virus particles such that virus particles are not released from infected cells.
An orally bioavailable, synthetic organic molecule targeting mitogen-activated protein kinase kinase (MAPK/ERK kinase or MEK) with potential antineoplastic activity. MEK inhibitor PD325901, a derivative of MEK inhibitor CI-1040, selectively binds to and inhibits MEK, which may result in the inhibition of the phosphorylation and activation of MAPK/ERK and the inhibition of tumor cell proliferation. The dual specific threonine/tyrosine kinase MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors.
The tosylate salt of sorafenib, a synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis.
A humanized monoclonal antibody directed against interferon-gamma (IFN-g) with immunomodulatory activity. Fontolizumab binds to and prevents the activity of IFN-g. This leads to a suppression of IFN-g-mediated signaling and thus a suppression of IFN-g immune related responses. IFN-g is a cytokine often overexpressed in various auto-immune diseases.
A bicyclic fatty acid derived from prostaglandin E1 and a chloride channel activator with laxative activity. Upon intake, lubiprostone specifically binds to and activates the type 2 chloride channel (ClC-2) in the apical membrane of the gastrointestinal epithelium. This produces an efflux of chloride ions, thereby drawing water into the gastrointestinal lumen. The resulting increased amounts of intestinal fluid soften the stool, increase motility, and improve bowel movements.
A sulfhydryl-based second-generation matrix metalloproteinase (MMP) inhibitor with potential antineoplastic activity. Rebimastat selectively inhibits several MMPs (MMP 1, 2, 8, 9, and 14), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis.
A response indicating that an individual is or has been unhappy.
Lattice corneal dystrophy type I is an eye disorder that affects the clear, outer covering of the eye called the cornea. The cornea must remain clear for an individual to see properly; however, in lattice corneal dystrophy type I, protein clumps known as amyloid deposits cloud the cornea, which leads to vision impairment. The cornea is made up of several layers of tissue, and in lattice corneal dystrophy type I, the deposits form in the stromal layer. The amyloid deposits form as delicate, branching fibers that create a lattice pattern.Affected individuals often have recurrent corneal erosions, which are caused by separation of particular layers of the cornea from one another. Corneal erosions are very painful and can cause sensitivity to bright light (photophobia). Lattice corneal dystrophy type I is usually bilateral, which means it affects both eyes. The condition becomes apparent in childhood or adolescence and leads to vision problems by early adulthood.
A fully human monoclonal antibody directed against the receptor activator of nuclear factor kappa beta ligand (RANKL) with antiosteoclast activity. Denosumab specifically binds to RANKL and blocks the interaction of RANKL with RANK, a receptor located on osteoclast cell surfaces, resulting in inhibition of osteoclast activity, a decrease in bone resorption, and a potential increase in bone mineral density. RANKL, a protein expressed by osteoblastic cells, plays an important role in osteoclastic differentiation and activation.
A galectin-binding polysaccharide derived from citrus pectin with potential antineoplastic activity. Apoptosis inducer GCS-100 binds to the carbohydrate-binding domain of the lectin galectin-3, which may result in apoptosis mediated through mitochondria/caspase activation cascades; this agent may overcome tumor growth mediated through anti-apoptotic protein Bcl-2, heat-shock protein 27 (Hsp27), and nuclear factor-kappa B (NF-kB). Galectin-3, a chimeric molecule consisting of both carbohydrate recognition and collagen-like domains, interacts with a variety of carbohydrate and protein ligands to form pentamers with unique crosslinking abilities; this lectin also exhibits anti-apoptotic properties, perhaps, in part, through the regulation of intracellular signaling pathways.
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
A congenital or acquired kidney disorder characterized by the presence of renal cysts.
Hearing loss caused by damage to the cochlea in the inner ear.
An influx of cells, generally leukocytes, in locations or numbers not normally found, without other features of inflammation.
The inflammation of one or more joints caused by a bacterial infection within the joint space. Symptoms include pain, stiffness, and decreased range of motion in the affected joint.
A cyclodiester antiviral prodrug with specific activity against hepatitis B virus (HBV). Pradefovir is specifically metabolized in the liver by hepatic enzymes, mainly by CYP4503A4, to adefovir. In turn, adefovir is phosphorylated by cellular kinases to its activated form adevofir diphosphate. By competing with the natural substrate dATP, the diphosphate form is incorporated into viral DNA and inhibits RNA-dependent DNA polymerase. This causes DNA chain termination and eventually results in an inhibition of HBV replication.
An abnormal shape of the vertebral bodies whereby the vertebral bodies are thick on one side and taper to a thin edge at the other.
Lewis-Sumner syndrome (LSS) is a rare acquired demyelinating polyneuropathy characterized by asymmetrical distal weakness of the upper or lower extremities and motor dysfunction with adult onset. It is considered to be a variant of chronic inflammatory demyelinating polyneuropathy.
A necrotic process affecting the peritoneum.
An abnormal communication between the oral cavity and the adjacent tissues.
Accumulation of an excessive amount of watery fluid in the visceral tissues. Symptoms include abdominal pain, nausea, vomiting, and diarrhea.
An opening in the prostate gland due to traumatic or pathologic processes.
An abnormal communication between the uterus and another organ.
Germ cell tumors of the central nervous system other than germinoma. This category includes teratoma, choriocarcinoma, embryonal carcinoma, and yolk sac tumor.
Blockage of the uterine outlet. Causes include uterine tumors and adhesions.
A rupture in the vaginal wall due to traumatic or pathologic processes.
The presence of abnormal calcium deposition in the liver.
Repetitive and compulsive picking of skin which results in tissue damage.
Leakage due to breakdown of a pharyngeal anastomosis.
A rupture in the wall of the ureter due to traumatic or pathologic processes.
Average of two or more properly measured readings at each of two or more visits after an initial screen with a systolic 120 to 139 mmHg or diastolic 80 to 89 mmHg.
An excessive reaction to stress caused by one's environment that may be characterized by feelings of emotional and physical exhaustion, coupled with a sense of frustration and failure.
A rupture through the testicular tissue.
Spontaneous development of hematomas (hematoma) or bruises without significant trauma.
Blockage of the normal flow of the intestinal contents in the rectum.
A bacterial or viral infectious process affecting an artery.
An infectious process affecting a cranial nerve.
Narrowing or stricture of the spermatic cord.
A rupture in the wall of the urethra due to traumatic or pathologic processes.
A lung function test result in which the lung capacity to absorb carbon monoxide is decreased.
A necrotic process involving the esophageal wall.
Leakage of urine due to breakdown of a bladder anastomosis.
Abnormally low testosterone production; possibly due to testicular dysfunction (primary hypogonadism) or hypothalamic-pituitary dysfunction (secondary hypogonadism) and may be congenital or acquired.
A necrotic process involving the rectal wall.
A necrotic process involving the area of the anus.
An infectious process affecting the small intestine.
A reduction in the strength of the muscles in the left side of the body.
Leakage due to breakdown of a fallopian tube anastomosis.
Decreased flexibility of a cervical spine joint.
A malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include carcinomas and sarcomas. Hematopoietic and lymphoid tissue malignancies are not considered solid neoplasms.
Leakage due to breakdown of a vaginal anastomosis.
Leakage due to breakdown of a small intestinal anastomosis.
A reduction in the strength of the upper limb muscles.
An adenosine derivative and selective A2A adenosine receptor agonist with coronary vasodilating activity. Upon administration, regadenoson selectively binds to and activates the A2A adenosine receptor, which induces coronary vasodilation. This leads to an increase in coronary blood flow and enhances myocardial perfusion. Compared to adenosine, regadenoson has a longer half-life and shows higher selectivity towards the A2A adenosine receptor. This agent is a very weak agonist for the A1 adenosine receptor and has negligible affinity for the A2B and A3 adenosine receptors.
An infectious process affecting the oral cavity, pharynx, and/or larynx.
An acute or chronic infectious process affecting a mucosal surface.
Leakage due to breakdown of a rectal anastomosis.
Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is characterized by utero-vaginal atresia in an otherwise phenotypically normal female with a normal 46,XX karyotype. Anomalies of the genital tract range from upper vaginal atresia to total mullerian agenesis with urinary tract abnormalities. It has an incidence of approximately 1 in 5,000 newborn girls (Cheroki et al., 2006). The abnormality of sexual development in MRKH syndrome is the same as that in the MURCS association (601076), in which cervicothoracic somite anomalies, unilateral renal agenesis, and conductive deafness are also seen. Mullerian aplasia and hyperandrogenism (158330) is caused by mutation in the WNT4 gene (603490). Familial cases of unilateral or bilateral renal agenesis in combination with mullerian anomalies have also been reported (see urogenital adysplasia, 191830).
An inflammatory process affecting the mucous membrane of the small intestine.
An infectious process affecting the duodenum.
A necrotic process affecting the soft tissues of the upper extremity.
Impaired functioning of the upper extremity.
An acute or chronic infectious process affecting the lips.
A necrotic process affecting the soft tissues of the lower extremity.
Fibrotic degeneration of the superficial soft tissues.
Leakage due to breakdown of a ureteral anastomosis.
Narrowing of the lumen of the vas deferens.
A necrotic process affecting the post-operative stoma area in the gastrointestinal tract.
An inflammatory process affecting the mucous membrane of the larynx.
An orally-available synthetic quinoline derivative with multidrug resistance modulating properties. Dofequidar binds to the drug-binding site of the transmembrane P-glycoprotein efflux pump and is preferentially transported from the cell, thereby blocking the efflux of other therapeutic agents.
An inflammatory process affecting the mucous membrane of the stomach.
An inflammatory process affecting the mucous membrane of the large intestine.
An intestinal stoma complication characterized by protrusion of the intestine above the abdominal surface.
Narrowing of the lumen of a gastrointestinal stoma.
A reduction in the strength of the muscles in the right side of the body.
Decreased flexibility of a lumbar spine joint.
Leakage due to breakdown of a urethral anastomosis.
A regimen consisting of gemcitabine and oxaliplatin used for the treatment of biliary adenocarcinoma, pancreatic cancer, hepatocellular cancer and testicular cancer. This regimen is currently being studied in a variety of other cancers.
An inflammatory process affecting the mucous membrane of the pharynx.
A perforation in the anatomic parts which are used in the construction of a urostomy.
Leakage due to breakdown of a vas deferens anastomosis.
Leakage due to breakdown of a large intestinal anastomosis.
Leakage due to breakdown of a spermatic cord anastomosis.
An inflammatory process affecting the mucous membrane of the trachea.
An infectious process affecting the vulva. Causative agents include human papillomavirus, herpes virus, Trichomonas, and Candida. Symptoms include itching and pain in the genital area and discharge.
An abnormal communication between the larynx and another organ or cavity.
Blockage of the normal flow of the small intestinal contents in the ileum.
An inflammatory process affecting the mucous membrane of the anus.
An inflammatory process affecting the mucous membrane of the esophagus.
An abnormal communication between the ileum and another organ or cavity.
An infectious process affecting the cecum.
A necrotic process occurring in the soft tissues of the abdominal wall.
Leakage of urine due to breakdown of a kidney anastomosis.
Leakage due to breakdown of a uterine anastomosis.
The orally bioavailable malate salt of an indolinone-based tyrosine kinase inhibitor with potential antineoplastic activity. Sunitinib blocks the tyrosine kinase activities of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor b (PDGFRb), and c-kit, thereby inhibiting angiogenesis and cell proliferation. This agent also inhibits the phosphorylation of Fms-related tyrosine kinase 3 (FLT3), another receptor tyrosine kinase expressed by some leukemic cells.
A gamma-cyclodextrin that functions as a reversal agent for the neuromuscular blocker ROCURONIUM BROMIDE.
A selective neurokinin 1 (NK1) receptor antagonist with potential antiemetic activity. Netupitant competitively binds to and blocks the activity of the human substance P/NK1 receptors in the central nervous system (CNS), thereby inhibiting NK1-receptor binding of the endogenous tachykinin neuropeptide substance P (SP), which may result in the prevention of chemotherapy-induced nausea and vomiting (CINV). SP is found in neurons of vagal afferent fibers innervating the brain-stem nucleus tractus solitarii and the area postrema, which contains the chemoreceptor trigger zone (CTZ), and may be elevated in response to chemotherapy. The NK-receptor is a G-protein receptor coupled to the inositol phosphate signal-transduction pathway and is found in both the nucleus tractus solitarii and the area postrema.
A benzamide and indazole derivative that acts as a TYROSINE KINASE inhibitor of the VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR. It is used in the treatment of advanced RENAL CELL CARCINOMA.
A vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with potential antineoplastic activity. BMS-582664 strongly binds to and inhibits VEGFR2, a tyrosine kinase receptor expressed almost exclusively on vascular endothelial cells; inhibition of VEGFR2 may result in inhibition of tumor angiogenesis, inhibition of tumor cell growth, and tumor regression. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=462556&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=462556&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C53397"" NCI Thesaurus)
The R-enantiomer of the racemic synthetic agent modafinil with central nervous system (CNS) stimulant and wakefulness-promoting activities. Although the exact mechanism of action has yet to be fully elucidated, armodafinil appears to inhibit the reuptake of dopamine by binding to the dopamine-reuptake pump, which leads to an increase in extracellular dopamine levels in some brain regions. This agent does not bind to or inhibit several receptors and enzymes that may be involved in sleep/wake regulation and is not a direct- or indirect-acting dopamine receptor agonist. Armodafinil has a longer half-life than modafinil.
A synthetic small molecule, derived from quinazolinone, with antineoplastic properties. Ispinesib selectively inhibits the mitotic motor protein, kinesin spindle protein (KSP), resulting in inhibition of mitotic spindle assembly, induction of cell cycle arrest during the mitotic phase, and cell death in tumor cells that are actively dividing. Because KSP is not involved in nonmitotic processes, such as neuronal transport, ispinesib may be less likely to cause the peripheral neuropathy often associated with the tubulin-targeting agents.
Pulmonary hypertension that results from another disorder (e.g., connective tissue disorder).
Serious INFLAMMATION of the LUNG in patients who required the use of PULMONARY VENTILATOR. It is usually caused by bacterial cross-infections in hospitals (NOSOCOMIAL INFECTIONS).
The agent paclitaxel linked to a biodegradable, water-soluble polyglutamate polymer with antineoplastic properties. The polyglutamate residue increases the water solubility of paclitaxel and allows delivery of higher doses than those achievable with paclitaxel alone. Paclitaxel promotes microtubule assembly and prevents microtubule depolymerization, thus interfering with normal mitosis.
A condition characterized by the complete absence of SEMEN. This disorder should be differentiated from AZOOSPERMIA, absence of sperm in the semen.
A synthetic cyclic peptide form of the naturally occurring posterior pituitary hormone oxytocin. Oxytocin binds to oxytocin receptors in the uterine myometrium, which triggers the G-protein coupled receptor signal transduction cascade that causes increased intracellular calcium concentrations. Increased calcium concentration levels activate myosin light chain kinase which, in turn, induces the formation of the contractile protein actomyosin. This stimulates uterine smooth muscle contractions. This agent also stimulates smooth muscles in the mammary glands, thereby causing lactation.
A mass of clotted blood or other formed elements, such as bubbles of air, calcium fragments, etc. brought by the blood from another vessel and forced into a smaller one, thus obstructing the circulation.
An inflammatory lesion comprised of lipoid material.
A malignant epithelial neoplasm characterized by the presence of neoplastic cells with hyperchromatic nuclei, small amount of cytoplasm, and peripheral nuclear palisading.
A locally aggressive neoplasm arising from tooth-forming tissues. It is more often intraosseous and less frequently extraosseous and occurs in the jaw. It is characterized by the presence of ameloblastoma-like epithelium, connective tissue stroma, ghost cells, and dysplastic dentin. Wide local resection is recommended for intraosseous neoplasms and enucleation for extraosseous neoplasms.
A rare, locally aggressive neoplasm arising from tooth-forming tissues. It occurs in the mandible and maxilla. It is characterized by the presence of odontogenic epithelium and adjacent myxoid tissue, fibrous stroma, and mineralized dental tissues.
An adenocarcinoma arising from the follicular cells of the thyroid gland. According to the degree of differentiation, it is classified either as differentiated carcinoma (extensive evidence of follicular cell differentiation), or poorly differentiated carcinoma (limited evidence of follicular cell differentiation).
A malignant neoplasm that has spread from its original site of growth to the leptomeninges.
A benign neoplasm characterized by the presence of spindle-shaped fibroblasts surrounding the hair follicle.
A lymphoma that arises from the breast. There is no history of extramammary breast lymphoma and ipsilateral axillary lymph node involvement does not exclude the diagnosis of primary breast lymphoma. Most patients present with a painless breast lump. The vast majority of cases are B-cell non-Hodgkin lymphomas. Diffuse large B-cell lymphoma, follicular lymphoma, and extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue are the most common types of primary non-Hodgkin lymphoma of the breast. Primary Hodgkin lymphoma of the breast is rare.
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
Any alteration in the inherited nucleic acid sequence of the genotype of an organism.
A condition that differs from the usual physical or mental state.
A series of biochemical reactions which occurs in a known sequence and can result in all or part of the initiation, progression or completion of a biological process or function.
A defined, decaffeinated green tea polyphenol mixture isolated from Camellia sinensis, a plant native to Asia, with antiviral and antioxidant activities and potential chemopreventive activity. Green tea extract contains antioxidant compounds, including flavonoids, vitamins and polyphenols such as epigallocatechin-3-gallate (EGCG), which may have antineoplastic properties. Consumption of green tea extract may confer chemopreventive protection against various cancers including those of the prostate, stomach, and esophagus.
A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.
Benign prostatic hyperplasia (BPH) refers to the nonmalignant growth of the prostate gland, and is histologically defined as hyperplasia of the prostate gland. BPH is an age-related phenomenon in men beginning at about age 40 years. BPH may result in prostatic enlargement and clinical symptoms most commonly affecting the lower urinary tract. These symptoms may be obstructive, including hesitancy, weak flow, and urinary retention, or irritative, including increased frequency and urgency. However, not all men with histologic BPH will develop prostatic enlargement or urinary symptoms (review by Roehrborn, 2005).
A benign nodular lesion protruding above the surface of the endometrium. It is composed of a fibrous stroma that contains thick-walled blood vessels and dilated endometrial glands. Polypectomy is the treatment of choice. Only few cases with recurrence have been reported.
An intramuscular suppuration of the large skeletal muscle groups. It is associated with INFECTION such as STAPHYLOCOCCUS AUREUS and PYODERMA. It was known as a tropical disease but is increasing among the immunocompromised (IMMUNOCOMPROMISED HOST). Symptoms include muscle pain, FEVER, and leucocytosis. It has been diagnosed by MRI SCANS.
A solution or suspension composed of an anionic surfactant and intended for administration to the hair and/or scalp.
A usually aggressive malignant bone-forming mesenchymal neoplasm arising from the bone. It usually involves the long bones and predominantly affects adolescents and young adults. Pain and a palpable mass are the most frequent clinical sign and symptom. It may spread to other anatomic sites, particularly the lungs.
A hormone made in the pituitary gland. In females, it acts on the ovaries to make follicles release their eggs and to make hormones that get the uterus ready for a fertilized egg to be implanted. In males, it acts on the testes to cause cells to grow and make testosterone.
An autosomal dominant disorder of lipid metabolism. It is caused by mutations of APOLIPOPROTEINS B, main components of CHYLOMICRONS and BETA-LIPOPROTEINS (low density lipoproteins or LDL). Features include abnormally low LDL, normal triglyceride level, and dietary fat malabsorption.
Leukoplakic lesions related to abnormal keratin fiber formation.
The presence of minimal changes visible by light microscopy but flattened and fused podocyte foot processes on electron microscopy in a person with nephrotic range proteinuria.
A renal functional disorder characterized by proteinuria, edema, hyperlipidemia and hypoalbuminemia. It results from damage to the renal vascular filtration apparatus. It is further characterized by an inflammatory reaction in the glomerular capillaries and the effacement of the surrounding epithelial cell foot processes worsening protein leakage. Sequelae may include hypertension, atherosclerosis, infection, hypercoagulablity and renal failure.
A malignant epithelial cellular proliferation characterized by the presence of atypical cells with large nuclei and abundant pale cytoplasm within the squamous epithelium of the nipple. In almost all cases there is an underlying intraductal breast carcinoma or intraductal and invasive carcinoma. The skin changes range from redness to eczematous appearance.
A sarcoma that arises from the bone. Representative examples are osteosarcoma and chondrosarcoma.
A conventional osteosarcoma characterized by the predominance of osteoid matrix.
A non-neoplastic or neoplastic (benign or malignant) disorder affecting the teeth.
A benign sweat gland cystic lesion that arises from the dermis. It is lined by a thin epithelial layer of cells with a slightly eosinophilic cytoplasm.
A cystic lesions that forms a benign tumor of an apocrine sweat gland.
A common benign hyaline cartilage neoplasm arising in the intramedullary bone. It is characterized by the presence of chondrocytes, low mitotic activity, and in some cases, a nodular pattern and calcification. The small bones of the hands and feet are the most frequently affected sites.
Disorder characterized by an emotionally constricted manner that is unduly conventional, serious, formal, and stingy, by preoccupation with trivial details, rules, order, organization, schedules, and lists, by stubborn insistence on having things one's own way without regard for the effects on others, by poor interpersonal relationships, and by indecisiveness due to fear of making mistakes.
A disorder characterized by HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; resulting from lack of phosphate reabsorption by the kidneys and possible defects in vitamin D metabolism.
An aggressive malignant mixed epithelial and mesenchymal tumor that arises from the uterine corpus. It usually affects elderly postmenopausal women and presents with vaginal bleeding. It is characterized by the presence of a malignant epithelial component that is usually glandular and a sarcomatous component.
A historical classification which is no longer used. It described acute glomerulonephritis, acute nephritic syndrome, or acute nephritis. Named for Richard Bright.
An experimental rat model of human membranous nephropathy characterized by complement activation and formation of subepithelial immune deposits in the glomerular capillary wall.
A type of renal tubular acidosis characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron. The urine cannot be acidified below a pH of 5.3, associated with acidemia and hypokalemia.
A rare non-Hodgkin or Hodgkin lymphoma that arises in and is confined to the lung at the time of diagnosis.
A vaccine composed of synthetic peptides derived from beta-human chorionic gonadotropin (hCG) conjugated to diphtheria toxoid. Vaccination with this peptide may elicit the host immune response against hCG-producing cancer cells.
A gastrointestinal stromal tumor that is characterized by a maximum diameter greater than 5 cm and equal or less than 10 cm (gastric localization), or greater than 2 cm and equal or less than 5 cm (intestinal localization) and no more than 5 mitotic figures per 50 high power fields.
A description of the life cycle of the West Nile virus.
A disorder of the skin characterized by loss or reduction of the skin color. It is caused by loss of melanocytes or abnormalities in melanin production.
Milroy disease is characterized by lower-limb lymphedema, present as pedal edema at (or before) birth or developing soon after. Occasionally it develops later in life. The severity of edema shows both inter- and intrafamilial variability. Swelling is usually bilateral but can be asymmetric. The degree of edema can progress but in some instances can improve, particularly in early years. Other features sometimes associated with Milroy disease include hydrocele (37% of males), prominent veins (23%), upslanting toenails (14%), papillomatosis (10%), and urethral abnormalities in males (4%). Cellulitis, which can damage the lymphatic vessels, occurs in approximately 20% of affected individuals, with infection significantly more likely in males than females.
A synthetic peptide that mimics the anti-angiogenic activity of the endogenous protein thrombospondin-1 (TSP-1). ABT-510 inhibits the actions of several pro-angiogenic growth factors important to tumor neovascularization; these pro-angiogenic growth factors include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)), hepatocyte growth factor (HGF), and interleukin 8 (IL-8). (NCI04)
A syndrome which occurs in individuals with a history of alcohol abuse. It is caused by prolonged alcohol-induced neurological damage and malnutrition including vitamin and electrolyte deficiencies. Clinical signs include altered mental status, visual impairment and decreased muscle coordination. The clinical course varies and is, in part, dependent upon the severity of symptoms at presentation. The prognosis is poor and worsens if alcohol abuse continues.
Twenty to 30% of early familial coronary heart disease (CHD) is ascribed to hypoalphalipoproteinemia, or high density lipoprotein deficiency. Although not initially recognized as a predisposing dyslipidemia, extensive epidemiologic work has implicated low high-density lipoprotein cholesterol (HDLC) levels in increased risk of cardiovascular disease, and low HDLC is considered to be a true dyslipidemic syndrome (Warnick and Wood, 1995).
Abnormality of the homeostasis (concentration) of a monoatomic ion.
A disorder of the arteries supplying the upper and lower extremity and the visceral organs. This includes the mesenteric arteries, the renal arteries and the aorta and excludes cerebrovascular arterial disease. Patients experience cramping and pain usually in the calves and thighs while walking. The symptoms subside with rest.
A benign neoplasm with exophytic and endophytic growth arising from the lateral nasal wall or the paranasal sinuses. It is characterized by the proliferation of columnar cells with oncocytic features. Microcysts containing mucin and neutrophils are present in the epithelium. Clinical manifestations include nasal obstruction and epistaxis. Occasionally, it is associated with the development or presence of a carcinoma, usually squamous cell carcinoma.
Impaired or altered function of the lower extremity.
A rare primary carcinoma of the thyroid gland, composed of groups of carcinoma cells, separated by a desmoplastic stroma. The architectural pattern resembles the lobulation that is present in thymomas and thymic carcinomas.
An undifferentiated pleomorphic sarcoma usually arising from the left atrium of the heart. It is characterized by the presence of fibrohistiocytic cells, giant cells, and spindle cells arrranged iin a storiform pattern. Clinical presentation includes signs and symptoms associated with left atrial hemodynamic changes.
A rare malignant mesenchymal tumor with skeletal muscle differentiation arising within the myocardium. It is characterized by the presence of small round spindle cells. Most cardiac rhabodomyosarcomas are of embryonal type and usually present in children and young adults.
The pathologic and/or clinical changes that result from treatment. The changes may include eradication of detectable disease, stabilization of disease, or disease progression.
A recombinant 28-amino-acid neuropeptide that is chemically identical or similar to the endogenous vasoactive intestinal peptide (VIP), with anti-inflammatory and anti-arthritic activities. This agent exerts a wide spectrum of anti-inflammatory activity by inhibiting macrophage functions, including phagocytosis, respiratory burst, and chemotaxis, and also by inhibiting T cell proliferation and decreasing lymphocyte migration. VIP has also been reported to inhibit the production of pro-inflammatory cytokines such as TNF alpha, interferon-gamma, IL-6, IL-12, to reduce the activity of inducible nitric oxide synthase and to enhance the production of the anti-inflammatory cytokines IL-10 and IL-1Ra. This agent exerts its anti-arthritic activity by reducing the titers of autoreactive antibodies against type II collagen (CII), a major factor in determining susceptibility to collagen-induced arthritis (CIA).
A recombinant fowlpox virus-based vaccine vector designed to express various tumor-associated peptide antigens. Strong CD8 cytotoxic T cell responses may be induced after prolonged immunization with fowlpox virus vaccines and have been associated with tumor regression. Fowlpox virus is an attractive vector because its genome is easy to manipulate and it does not multiply in human tissues. (NCI05)
A class of nutrients that are in the water-soluble B-vitamin family. B vitamins include thiamine, riboflavin, niacin (nicotinic acid), niacinamide (nicotinamide), the vitamin B6 group (including pyridoxine, pyridoxal, pyridoxamine), biotin, pantothenic acid, folic acid, and possibly para-aminobenzoic.
Lobular Cancerization (or cancerization of lobules, COL) is the presence in a lobule of ductal carcinoma in situ (DCIS) tumor cells with preservation of the normal lobular pattern. It appears to represents a variation in the growth pattern of DCIS, not secondary extension of DCIS into a lobule.
A recombinant human proteolytic fragment of the C-terminal end of type XVIII collagen. Endostatin induces microvascular endothelial cell apoptosis and inhibits endothelial proliferation and angiogenesis, which may result in a reduction in tumor burden. This agent also may decrease hepatic metastasis by inhibiting proinflammatory cytokines and vascular cell adhesion molecule (VCAM)-dependent cell attachment to the hepatic microvasculature. (NCI04)
A variation from processes or procedures defined in a protocol. Deviations usually do not preclude the overall evaluability of subject data for either efficacy or safety, and are often acknowledged and accepted in advance by the sponsor. (CDISC Glossary)
Therapeutically inactive dye or coloring agent that is a component of pharmaceutical product. There are the more than 100 excipient colors approved by the FDA for pharmaceutical use.
A congenital anatomic abnormality manifested during the neonatal period.
Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.
A pharmaceutical preparation containing a mixture of arg-vasopressin and lys-vasopressin. It is prepared by synthesis or obtained from neurohypophyseal extract of domestic animals. Its vasopressor activity is not less than 300 USP vasopressin units per mg.
A person who was assigned to the male gender at birth based on physical characteristics but who self-identifies psychologically and emotionally as female.
The perception of sudden or brief bursts (flashes) of light.
A condition or event that is attributed to the adverse event and is the result or conclusion of the adverse event.
Decreased period of time required for the concentration or amount of drug in the body to be reduced to exactly one-half of a given concentration or amount.
A structural change in genomic DNA where the 5' to 3' order of a nucleotide sequence is completely reversed to the 3' to 5' order relative to its adjacent sequences. This inversion is termed either pericentric, if it includes the centromere of a chromosome, or pancentric, if it excludes the centromere. An inversion mutation abnormality may be heritable or occur somatically.
Fusion of two genes or segments of genes that were previously separated prior to a mutation abnormality such as translocation. A gene fusion abnormality results in the formation of a new genetic unit that typically exhibits altered functional characteristics. This type of mutation abnormality can be either heritable or occur somatically.
An increase in the copy number of a particular gene. This type of abnormality can be either inherited or somatic.
Problem with all or part of an implanted or invasive medical device being completely expelled from its intended location within the body.
Paget disease of the nipple without invasive carcinoma and/or carcinoma in situ in the underlying breast parenchyma. (from AJCC 6th and 7th Ed.)
Generation of an extra copy of a particular gene in the genome. A gene duplication abnormality may occur by gene amplification, random breakage and reunion, retrotransposition or unequal crossing-over at meiosis. A gene duplication abnormality can be either heritable or somatic.
A class of synthetic peptides based on the sequences of carcinoembryonic antigen (CEA), a tumor-associated antigen overexpressed in several cancer cell types. These peptides may be used in vaccination against cancers.
A group of inherited metabolic disorders characterized by the intralysosomal accumulation of sulfur-containing lipids (SULFATIDES), including SULFOGLYCOSPHINGOLIPIDS normally found in the MYELIN SHEATH of the brain. These disorders are caused by defective degradative enzymes leading to substrate accumulation (or storage).
A mild inflammatory tissue reaction; it can be caused by physical contact with an irritant or can be a local response to a systemic trigger.
The strength of the active ingredient(s) is not provided.
A change in the amino acid sequence of a wild-type protein. This alteration typically occurs due to a mutation of the gene that encodes the protein. The change in amino acid sequence may enhance, reduce, abolish or have no effect on protein activity.
Translation of a truncated form of a wild-type protein that originates from a mutation or mutations in the coding sequence of a gene. Genetic alterations that yield truncated protein products include frameshift mutations, nonsense mutations or splice site mutations. The activity of a truncated protein is usually reduced or abolished in comparison to the activity of the wild-type protein.
Abnormally high level of lipids in blood.
Recombinant forms of endogenous Heparin-binding Neurotrophic factors(NCI)
Golden brown or gray deposits with a clockwise, whorl-like distribution in the inferior interpalpebal portion of the cornea.
ABC Transporter Inhibition involves interference with, or restraint of, the activities of cell membrane glycoproteins selectively permeable to P-glycoprotein substrates.
A small, cyclic pentapeptide vascular-targeting agent with potential antineoplastic and antiangiogenic activities. ADH-1 selectively and competitively binds to and blocks N-cadherin, which may result in disruption of tumor vasculature, inhibition of tumor cell growth, and the induction of tumor cell and endothelial cell apoptosis. N-cadherin, a cell- surface transmembrane glycoprotein of the cadherin superfamily of proteins involved in calcium-mediated cell-cell adhesion and signaling mechanisms; may be upregulated in some aggressive tumors and the endothelial cells and pericytes of some tumor blood vessels.
A synthetic lysyl prodrug of the amino-substituted flavone derivate aminoflavone with antiproliferative and antineoplastic activities. AFP464 is rapidly converted to aminoflavone in plasma. Aminoflavone activates the aryl hydrocarbon receptor (AhR) signaling pathway leading to an increase in cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1A2 (CYP1A2) expression and, to a lesser extent, an increase in cytochrome P450 1B1 (CYP1B1) expression. Subsequently, aminoflavone is metabolized to toxic metabolites by the cytochromome P450 enzymes that it induces; these toxic metabolites covalently bind to DNA, resulting in the phosphorylation of p53, the induction of the p53 downstream target p21Waf1/Cip1, and apoptosis. Pulmonary toxicity may be dose-limiting.
A cyclin-dependent kinase (CDK) inhibitor with antineoplastic activity. AG-024322 selectively inhibits cyclin-dependent kinases (particularly CDK1,2 and 4), enzymes that regulate cell cycle progression. Inhibition of CDK may result in cell cycle arrest, induction of apoptosis, and inhibition of DNA replication and tumor cell proliferation.
A cell-based vaccine composed of autologous antigen-presenting peripheral blood mononuclear cells (enriched for a dendritic cell fraction) that have been exposed to a recombinant protein consisting of granulocyte-macrophage colony-stimulating factor (GM-CSF) fused to prostatic-acid phosphatase (PAP), a protein expressed by prostate cancer cells. Upon administration, the vaccine may stimulate an antitumor T-cell response against tumor cells expressing PAP. (NCI05)
A proprietary vaccine adjuvant composed of the inorganic compound aluminum phosphate mixed with 3-deacylated monophosphoryl lipid A, a derivate of the bacterial endotoxin. The aluminum component of this adjuvant binds to the protein conjugate, resulting in improved antigenicity, whereas the modified lipid A component enhances the immune responses by activating monocytes, macrophages and cytokines. Combined with vaccine antigens, AS04 adjuvant may help to boost the host's immune responses.
A synthetic non-toxic tellurium derivative, structurally similar to cisplatin, with immunostimulatory and anti-hair loss properties. Ammonium trichlorotellurate induces production of colony stimulating factor (CSF), interleukin-2 (IL-2), and IL-2 receptors by increasing the calcium ion influx through the cell membrane and subsequently exerts its immunostimulatory effects through the CSF-mediated increase in macrophage/granulocytes. This agent is also a potent inducer of interferon and a spectrum of cytokines such as IL-1, IL-6, and tumor necrosis factor (TNF). In animal studies, ammonium trichlorotellurate exerts its anti-hair loss effect by inducing anagen and obstructing spontaneous catagen via promoting follicular keratinocyte proliferation and interfering with terminal differentiation, respectively.
A small peptide antagonist of integrin alpha5beta1 with potential antineoplastic activity. ATN-161 selectively binds to and blocks the receptor for integrin alpha5beta1, thereby preventing integrin alpha5beta1 binding. This receptor blockade may result in inhibition of endothelial cell-cell interactions, endothelial cell-matrix interactions, angiogenesis, and tumor progression. Integrin alpha5beta1 is expressed on endothelial cells and plays a crucial role in endothelial cell adhesion and migration.
An orally available, synthetic small molecule with potential antineoplastic activity. AVN944 inhibits inosine monosphosphate dehydrogenase (IMPDH), an enzyme involved in the de novo synthesis of guanosine triphosphate (GTP), a purine molecule required for DNA and RNA synthesis. Inhibition of IMPDH deprives cancer cells of GTP, resulting in disruption of DNA and RNA synthesis, inhibition of cell proliferation, and the induction of apoptosis. AVN944 appears to have a selective effect on cancer cells in that deprivation of GTP in normal cells results in a temporary slowing of cell growth only. IMPDH is overexpressed in some cancer cells, particularly in hematological malignancies.
An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. AZD0530 is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and their effects on cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, AZD0530 inhibits Src kinase-mediated osteoclast bone resorption. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=453588&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=453588&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48378"" NCI Thesaurus)
An infrequent pituitary gland adenoma composed of cells showing immunoreactivity for prolactin and less often growth hormone. Electron microscopic studies reveal giant mitochondria, a finding not present in any other type of pituitary gland adenomas.
Acute myelomonocytic leukemia without an abnormal eosinophilic component in the bone marrow.
A point mutation involving the substitution of Cytosine (a pyrimidine base) for Adenosine (a purine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A point mutation involving the substitution of Guanosine (a purine base) for Adenosine (a purine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A point mutation involving the substitution of Thymidine (a pyrimidine base) for Adenosine (a purine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A nonreplicating adenoviral vector (adenovector) encoding the melanoma differentiation-associated 7 gene (MDA7) with potential antineoplastic activity. After intratumoral injection and adenovector-mediated gene transfer of MDA7 into tumor cells, the expressed MDA7 transgene may inhibit tumor cell proliferation and induce tumor cell apoptosis.
A usually non-functioning variant of adrenal cortex adenoma, composed of large cells with abundant granular eosinophilic cytoplasm.
A benign neoplasm probably arising from mesothelial inclusions in the adrenal gland tissue. (NCI05)
A rare malignant soft tissue neoplasm arising from the vascular endothelium of the adrenal gland.
A benign or malignant neoplasm arising from the adrenal medulla. It combines morphologic characteristics of pheochromocytoma and neuroectodermal tumors such as neuroblastoma, ganglioneuroma, ganglioneuroblastoma, or peripheral nerve sheath tumors.
Cardiac rhabdomyoma occurring in adults. It is characterized by the presence of neoplastic striated muscle cells with eosinophilic granular cytoplasm and increased cellularity.
An extraskeletal myxoid chondrosarcoma occurring in adults.
A hepatocellular carcinoma that occurs during adulthood and has spread extensively to other anatomical sites or is no longer responding to treatment.
A clinical stage II or IV non-Hodgkin lymphoma with up to three of the following risk factors: albumin level less than 4.0 g/dl, hemoglobin level of less than 10.5 g/dl, male sex, forty-five years of age or older, stage IV disease, white cell count of at least 15,000 per cubic millimeter, absolute lymphocytic count of less than 600 per cubic millimeter or a lymphocytic count of less than 8% of the total white cell count.
A clinical stage II or IV non-Hodgkin lymphoma with at least four of the following risk factors: albumin level less than 4.0 g/dl, hemoglobin level of less than 10.5 g/dl, male sex, forty-five years of age or older, stage IV disease, white cell count of at least 15,000 per cubic millimeter, absolute lymphocytic count of less than 600 per cubic millimeter or a lymphocytic count of less than 8% of the total white cell count.
An adenoma of the adrenal cortex that produces aldosterone. It may be associated with Conn syndrome. Clinical presentation includes hypertension, hypokalemia, and muscle weakness.
A very rare ameloblastic carcinoma that originates from a pre-existing intraosseous benign ameloblastoma.
A very rare ameloblastic carcinoma that originates from a pre-existing extraosseous benign ameloblastoma.
The trihydrate form of a phosphorylated aminosulfhydryl compound. After dephosphorylation of amifostine by alkaline phosphatase to an active free sulfhydryl (thiol) metabolite, the thiol metabolite binds to and detoxifies cytotoxic platinum-containing metabolites of cisplatin and scavenges free radicals induced by cisplatin and ionizing radiation. The elevated activity of this agent in normal tissues results from both the relative abundance of alkaline phosphatase in normal tissues and the greater vascularity of normal tissues compared to tumor tissues. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39741&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39741&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C488"" NCI Thesaurus)
The hydrochloride salt of a third-generation synthetic 9-amino-anthracycline with antineoplastic activity. Amrubicin intercalates into DNA and inhibits the activity of topoisomerase II, resulting in inhibition of DNA replication, and RNA and protein synthesis, followed by cell growth inhibition and cell death. This agent has demonstrated a higher level of anti-tumor activity than conventional anthracycline drugs without exhibiting any indication of the cumulative cardiac toxicity common to this class of compounds.
A soft tissue neoplasm composed of acellular amyloid material.
Amyloidogenesis is the formation or growth of amyloid structures, implicated in many human diseases including Alzheimer s disease (AD), Parkinson s disease (PD), type II diabetes, and spongiform encephalopathies. In these disease states, normally soluble proteins aggregate as amyloidogenic insoluble fibrils that accumulate in affected tissues or organs.
A rare adenoma of the adrenal cortex that produces androgens. Female patients usually have symptoms related to virilism.
A neoplasm arising from the anterior lobe of the pituitary gland. The vast majority are adenomas.
Antigen Sensitization is a process of immunization with an antigen preparation that renders an immune-response involving generation of antibodies against the specific antigen(s) injected.
A carcinoma with apocrine differentiation arising from the sweat glands. It presents as single or multiple nodular lesions which may be ulcerated or hemorrhagic and is usually in the axilla and less often in the anogenital region. It grows in the dermis and infiltrates subcutaneous tissues. It is characterized by the presence of large cells with abundant eosinophilic cytoplasm and large often vesicular nuclei. Most cases are slow growing tumors and have a prolonged course.
A circumscribed neoplasm arising from the glandular epithelium of the appendix. Morphologically, it is characterized by a proliferation of neoplastic glandular cells and it is associated with dysplasia. According to the growth pattern, it may be classified as tubular, villous, or tubulovillous. The dysplasia is classified as mild, moderate, or severe.
A benign adipose tissue neoplasm involving the wall of the appendix.
A carcinoma that arises from the appendix. It is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
An adenocarcinoma arising from the appendix, characterized by the presence of mucinous stroma formation.
An aggressive, poorly differentiated neuroendocrine malignant neoplasm arising from the wall of the appendix. It is characterized by the presence of small malignant cells, necrotic changes, and an increased mitotic rate.
An adenoma arising from the appendix. It is characterized by the presence of tubular epithelial structures and it is associated with dysplasia.
A neuroendocrine tumor that arises from the appendix. It does not show the morphologic characteristics of typical carcinoid tumors (neoplastic cells forming solid nests). In contrast, the tumor cells form small discrete tubules.
An adenoma arising from the appendix. It is characterized by the presence of tubular and villous epithelial structures and it is associated with dysplasia.
A high grade carcinoma arising from the appendix, characterized by the absence of glandular or squamous differentiation.
Consisting of abnormally decreased sensitivity, particularly to touch in the arm or hand.
Features commonly associated with lymphoma, including fever above 38C, drenching night sweats, and weight loss of more than 10% of body mass in the previous 6 months. B symptoms are signs of a poor prognosis in patients with lymphoma.
A change in the nucleotide sequence of the FLCN gene.
A small molecule compound with potential antineoplastic activities. BI 2536 binds to and inhibits Polo-like kinase 1 (Plk1), resulting in mitotic arrest, disruption of cytokinesis, and apoptosis in susceptible tumor cell populations. Plk1, a serine/threonine-protein kinase, is a key regulator of multiple processes fundamental to mitosis and cell division.
A change in the nucleotide sequence of the BLM gene.
A sporadic or familial pheochromocytoma that is confined to the adrenal gland and does not have any metastatic potential. The majority of cases are sporadic, and usually unilateral. Familial cases are usually bilateral.
A rare, benign neoplasm, usually arising from the non-metaphyseal regions of long bones or pelvis. It is characterized by the presence of fibroblastic spindle cells arranged in a whorled storiform pattern, osteoclast-like giant cells, foam cells, inflammatory cells, hemosiderin deposition and stromal hemorrhage.
A benign mesenchymal neoplasm arising from the pilar sheath of the hair follicle. Representative examples include fibrofolliculoma, perifollicular fibroma, pilar leiomyoma, and trichogenic myxoma.
Primary cutaneous marginal zone lymphoma of mucosa-associated lymphoid tissue that arises from chronically stimulated lymphoid tissue in the skin in response to Borrelia burgdoferi infection.
An extract of soybeans enriched in Bowman-Birk inhibitor (BBI), a soybean-derived, 71-amino acid, polypeptide and serine protease inhibitor with potential chemopreventive activity. Bowman-Birk inhibitor contains distinct inhibitory sites for trypsin and chymotrypsin. Although the exact mechanism by which BBI suppresses carcinogenesis is unknown, its antiproliferative activity appears to be linked to the chymotrypsin inhibitory region.
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, endoscopy, biopsy or laboratory testing.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes. TNM pathologic regional lymph nodes findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system.
Breast cancer in which there is no evidence of distant metastasis. (from AJCC 6th Ed.)
Breast cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Breast cancer in which the status of distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Breast cancer without histological evidence of regional lymph node involvement (no isolated tumor cell cluster greater than 0.2mm), and in which no examination for isolated tumor cells is performed. (from AJCC 6th Ed.)
Breast cancer without histological evidence of regional lymph node involvement, and negative morphologic findings for isolated tumor cells using any morphologic technique (including hematoxylin-eosin and/or immunohistochemistry). (from AJCC 6th Ed.)
Breast cancer without histological evidence of regional lymph node involvement, and positive morphologic findings for isolated tumor cells (ITCs) using any morphologic technique (including hematoxylin-eosin and/or immunohistochemistry), and no ITC cluster greater than 0.2 mm. (from AJCC 6th Ed.)
Breast cancer without histological evidence of regional lymph node involvement, and with negative molecular findings by RT-PCR. (from AJCC 6th and 7th Ed.)
Breast cancer with positive molecular findings by RT-PCR, but without histological or immunohistochemical evidence of regional lymph node involvement. (from AJCC 6th and 7th Ed.)
Breast cancer with metastasis to 1 to 3 axillary lymph nodes, and/or internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent. (from AJCC 6th Ed.)
Breast cancer with metastasis in 1 to 3 axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm). (from AJCC 6th and 7th Eds.)
Breast cancer with metastasis in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent. (from AJCC 6th Ed.)
Breast cancer with metastasis in 1 to 3 axillary lymph nodes and in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent. (from AJCC 6th Ed.)
Breast cancer with micrometastasis (greater than 0.2 mm, none greater than 2.0 mm). (from AJCC 6th Ed.)
Breast cancer with metastasis in 4 to 9 axillary lymph nodes or in clinically apparent internal mammary lymph nodes in the absence of axillary lymph node metastasis. (from AJCC 6th Ed.)
Breast cancer with metastasis in 4 to 9 axillary lymph nodes (at least 1 tumor deposit greater than 2.0 mm). (from AJCC 6th and 7th Eds.)
Breast cancer with metastasis in clinically apparent internal mammary lymph nodes in the absence of axillary lymph node metastases. (from AJCC 6th Ed.)
Breast cancer with metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes, or in clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes with clinically negative microscopic metastasis in internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes. (from AJCC 6th Ed.)
Breast cancer with metastases in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm); or metastases to the infraclavicular (level III axillary) lymph nodes. (from AJCC 6th and 7th Eds.)
Breast cancer with metastasis in clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent. (from AJCC 6th Ed.)
Breast cancer with metastasis in ipsilateral supraclavicular lymph nodes. (from AJCC 6th and 7th Eds.)
Breast cancer in which regional lymph nodes cannot be assessed (e.g., previously removed, or not removed for pathologic study). (from AJCC 6th and 7th Eds.)
Breast cancer with no evidence of primary tumor. (from AJCC 6th and 7th Eds.)
Breast cancer with tumor size 2.0 cm or less in greatest dimension. (from AJCC 6th and 7th Ed.)
Breast cancer with tumor size more than 0.1 cm, but not more than 0.5 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Breast cancer with tumor size more than 0.5 cm, but not more than 1.0 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Breast cancer with tumor size more than 1.0 cm, but not more than 2.0 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Breast cancer with tumor size 0.1 cm or less in greatest dimension (microinvasion). (from AJCC 6th and 7th Eds.)
Breast cancer with tumor size more than 2.0 cm, but not more than 5.0 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Breast cancer with tumor size more than 5.0 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Breast cancer with tumor of any size with direct extension to chest wall or skin, but only as described in pT4 sub-categories, in accordance with TNM guidelines. (from AJCC 6th and 7th Eds.)
Breast cancer with extension to the chest wall, not including the pectoralis muscle. (from AJCC 6th and 7th Eds.)
Breast cancer with ulceration and/or ipsilateral satellite nodules and/or edema (including peau d'orange) of the skin, which do not meet the criteria for inflammatory carcinoma. (from AJCC 6th and 7th Eds.)
Breast cancer with extension to the chest wall, not including the pectoralis muscle, and with edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast. (from AJCC 6th and 7th Eds.)
Breast cancer meeting the clinical-pathologic criteria of inflammatory carcinoma. (from AJCC 6th and 7th Eds.)
Breast cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Breast cancer with a finding of ductal carcinoma in situ. (from AJCC 6th and 7th Ed.)
Breast cancer with a finding of lobular carcinoma in situ. (from AJCC 6th and 7th Ed.)
Breast cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
An invasive carcinoma of the breast showing differentiation towards cartilaginous structures.
A second generation ATP-competitive anthrapyrazolone c-Jun N terminal kinase (JNK) inhibitor with potential antineoplastic activity. Based on the chemistry of SP600125, another anthrapyrazolone inhibitor of JNK, CC-401 competitively binds the ATP binding site of JNK, resulting in inhibition of the phosphorylation of the N-terminal activation domain of transcription factor c-Jun; decreased transcription activity of c-Jun; and a variety of cellular effects including decreased cellular proliferation.
An ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors.
An indication that expression of CD4 has been detected in a sample of neoplastic cells.
The hydrochloride salt of an orally bio-available quinazoline with potential antineoplastic and radiosensitizing activities. Canertinib binds to the intracellular domains of epidermal growth factor receptor tyrosine kinases (ErbB family), irreversibly inhibiting their signal transduction functions and resulting in tumor cell apoptosis and suppression of tumor cell proliferation. This agent also acts as a radiosensitizing agent and displays synergistic activity with other chemotherapeutic agents.
The lipophilic 5'-elaidic acid ester of the deoxycytidine analog cytosine arabinoside (cytarabine; Ara-C) with potential antineoplastic activity. As a prodrug, CP-4055 is converted intracellularly into cytarabine triphosphate by deoxycytidine kinase and subsequently competes with cytidine for incorporation into DNA, thereby inhibiting DNA synthesis. Compared to cytarabine, CP-4055 shows increased cellular uptake and retention, resulting in increased activation by deoxycytidine kinase to cytarabine triphosphate, decreased deamination and deactivation by deoxycytidine deaminase, and increased inhibition of DNA synthesis. This agent also inhibits RNA synthesis, an effect not seen with cytarabine. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=463939&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=463939&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C53401"" NCI Thesaurus)
A human monoclonal antibody directed against the insulin-like growth factor type I receptor (IGF1R) with potential antineoplastic activity. CP-751871 selectively binds to IGF1R, preventing insulin-like growth factor type 1 (IGF1) from binding to the receptor and subsequent receptor autophosphorylation. Inhibition of IGF1R autophosphorylation may result in a reduction in receptor expression on tumor cells that express IGF1R, a reduction in the anti-apoptotic effect of IGF, and inhibition of tumor growth. IGF1R is a receptor tyrosine kinase expressed on most tumor cells and is involved in mitogenesis, angiogenesis, and tumor cell survival. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=456793&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=456793&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C52187"" NCI Thesaurus)
A mucosa-associated lymphoid tissue lymphoma that arises from the small intestine and it is associated with Campylobacter jejuni infection.
A cancer finding in the TNM system that is relevant to the diagnosis of cancer.
Aspects of the context prevent the evaluation needed to determine a value.
The tightening of scar tissue that forms around the implant.
A microscopic finding indicating the infiltration of the capsule that surrounds an organ by a malignant cellular population.
A rare, highly aggressive and lethal carcinoma that affects children and young adults. It arises from midline epithelial structures, most commonly the head, neck, and mediastinum. It is a poorly differentiated carcinoma and is characterized by mutations and rearrangement of the NUT gene. A balanced translocation t(15;19) is present that results in the creation of a fusion gene involving the NUT gene, most commonly BRD4-NUT fusion gene.
A biphasic synovial sarcoma arising from the heart.
A hemangioma arising from the heart. It is characterized by the presence of cavernous vascular spaces.
An intermediate fibroblastic neoplasm arising from the heart. It is characterized by the presence of spindle-shaped fibroblasts and myofibroblasts, and a chronic inflammatory infiltrate composed of eosinophils, lymphocytes, and plasma cells.
A hemangioma arising from the myocardium.
A monophasic synovial sarcoma arising from the heart.
A synovial sarcoma arising from the heart.
Tooth decay that has invaded the dentin, creating dentin that is partially demineralized and containing mineral crystals in the tubules.
Any apoptotic process that involves pathways that activate intracellular proteolytic caspases.
Any apoptotic process that does not involve pathways that activate intracellular proteolytic caspases.
A morphologic variant of angioleiomyoma characterized by the presence of markedly dilated vascular channels.
The sodium salt form of cefamandole, a beta-lactam, second-generation cephalosporin antibiotic with bactericidal activity. Cefamandole binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
An intramuscular myxoma with increased cellularity and increased numbers of collagen fibers and blood vessels.
The monohydrate form of cephradine, a beta-lactam, first-generation cephalosporin antibiotic with bactericidal activity. Cephradine monohydrate binds to and inactivates penicillin-binding proteins (PBP) located on the inner membrane of the bacterial cell wall. PBPs participate in the terminal stages of assembling the bacterial cell wall, and in reshaping the cell wall during cell division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
A rare benign lesion that arises from the rib cage and affects infants. It results in the formation of a mass which is composed of spindle cells, cartilage, and hemorrhagic cysts. Surgical resection is usually curative.
Children affected by toxins may be due to silicone breast implants and their effects on unborn children and from breastfeeding.
A chimeric, IgG1 monoclonal antibody directed against anionic phospholipids with potential antineoplastic activity. Bavituximab binds to anionic phospholipids in a beta 2-glycoprotein I-dependent manner, inhibiting tumor growth by stimulating antibody-dependent cellular cytotoxicity (ADCC) to tumor vessels.
Mucosa-associated lymphoid tissue lymphoma that arises from the ocular adnexa and caused by stimulation of lymphoid tissue due to Chlamydia psittaci bacterial infection.
A medulloblastoma composed of malignant cells with hyperchromatic nucleus and scanty cytoplasm. Homer Wright rosettes may be present.
A low grade fibromyxoid sarcoma that may have poorly formed collagen rosettes, but lacks prominent, well formed collagen rosettes.
A morphologic variant of intrahepatic cholangiocarcinoma composed of malignant glandular epithelium, an abundant fibrous stroma, and the presence of clear cells. Clinical symptoms include abdominal pain, weight loss and malaise.
A large cell lung carcinoma characterized by a predominance of clear cells that may or may not contain glycogen.
A morphologic variant of follicular carcinoma of the thyroid gland characterized by the predominance of malignant follicular clear cells. These cells lack the nuclear features that characterize the papillary carcinomas of the thyroid gland.
A morphologic variant of papillary carcinoma of the thyroid gland characterized by the predominance of malignant follicular clear cells. These cells have the nuclear features that characterize the papillary carcinomas of the thyroid gland.
TNM staging performed with access to clinical information only.
A substance used to increase the quality or quantity of a sample harvest.
An adenocarcinoma that arises from the colonic glandular epithelium and invades the lamina propria or muscularis mucosa but not the submucosa.
An adenoma that arises from the colon. It is characterized by prominent serration of the glands and the presence of generalized low-grade dysplasia.
An invasive adenocarcinoma of the colon characterized by the presence of malignant glandular epithelial cells which contain prominent intracytoplasmic mucin (signet ring cells). The signet ring cells constitute more than 50% of the malignant cells.
An unusual colorectal carcinoma characterized by the presence of glandular and squamous carcinomatous components. The two carcinomatous components may be admixed within the tumor, or the two may appear separately in different areas.
A rare, invasive colorectal adenocarcinoma characterized by the presence of sheets of malignant epithelial cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. It usually has a favorable prognosis.
An invasive colorectal adenocarcinoma characterized by the presence of extracellular mucin pools that contain malignant glandular epithelial structures. The extracellular mucin pools occupy more than 50% of the malignant lesion.
An invasive colorectal adenocarcinoma characterized by the presence of malignant glandular epithelial cells with prominent intracytoplasmic mucin resulting in the displacement of the nuclei. The malignant glandular cells with intracytoplasmic mucin constitute more than 50% of the malignant cellular infiltrate.
An aggressive, high-grade, and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the colon or rectum. It is characterized by the presence of malignant small cells.
A very rare colorectal carcinoma characterized by the presence of a malignant squamous cell infiltrate.
An invasive malignant epithelial tumor that arises from the colon or rectum. There is no morphologic, immunophenotypic, or molecular biological evidence of glandular or squamous differentiation.
A columnar cell lesion characterized by the presence of enlarged terminal ductal lobular units with dilated acini. The acini are lined by one or two layers of columnar epithelial cells. Apical cytoplasmic snouts may be present, but they are not prominent. Secretions may be present in the lumina of the dilated acini.
A columnar cell lesion characterized by the presence of enlarged terminal ductal lobular units with dilated acini. The acini are lined by one or two layers of columnar epithelial cells. Cytologic atypia is present.
A columnar cell lesion characterized by the presence of enlarged terminal ductal lobular units with dilated acini. The acini are lined by more than two layers of columnar epithelial cells. Prominent apical cytoplasmic snouts are present. Secretions are often present in the lumina of the dilated acini.
A columnar cell lesion characterized by the presence of enlarged terminal ductal lobular units with dilated acini. The acini are lined by more than two layers of columnar epithelial cells. Cytologic atypia is present. Prominent apical cytoplasmic snouts and intraluminal secretions are also present.
A morphologic spectrum of lesions that arise in the terminal ductal lobular units of the breast parenchyma. These lesions are characterized by the presence of columnar epithelial cells that line dilated terminal ductal lobular units. Cytological and architectural atypia may be absent or minimal, or significant enough to raise the possibility of atypical ductal hyperplasia or ductal carcinoma in situ. Columnar cell lesions are frequently found in breast biopsies but their biologic significance is not known.
A primary thymic epithelial neoplasm, characterized by the presence of at least two distinct areas, one representing a thymoma and the other a carcinoma. The most aggressive component usually determines the clinical outcome.
When the permission to do something is rescinded or withdrawn.
The patient becomes contaminated from contact with blood/fluids on a device.
An interaction in which one entity regulates, modifies, or otherwise influences another.
A morphologic variant of dermatofibrosarcoma protuberans characterized by the presence of spindle-shaped fibroblastic cells, histiocytic cells, and a storiform growth pattern.
An adenoma of the adrenal cortex that produces cortisol. It may be associated with Cushing syndrome. Clinical presentation includes weight gain, round face, easy bruising, muscle weakness, emotional changes, hirsutism, and hypertension.
A heterocyclic compound with anticoagulant activity. It is found naturally in many plants or can be prepared synthetically. A coumarin compound contains the 1,2-benzopyrone structure.
A split located on a leaflet of a heart valve that prevents its complete closing, which can result in valvular dysfunction.
An aggressive mature T-cell non Hodgkin lymphoma involving the skin. It is characterized by the presence of a polymorphic cellular infiltrate which contains neoplastic small to medium sized T-lymphocytes.
A morphologic variant of cutaneous fibrous histiocytoma characterized by the presence of spindle-shaped fibrohistiocytic cells and increased cellularity.
A morphologic variant of cutaneous fibrous histiocytoma characterized by the presence of epitheloid fibrohistiocytic cells.
A morphologic variant of cutaneous fibrous histiocytoma characterized by the presence of spindle-shaped fibrohistiocytic cells and associated acanthosis.
A morphologic variant of cutaneous fibrous histiocytoma characterized by the presence of xanthomatous fibrohistiocytic cells, giant cells, and hemosiderin deposition.
An aggressive cutaneous lymphoma of mature, activated gamma/delta T-lymphocytes. It usually presents with disseminated plaques and nodules. Involvement of mucosal sites is frequent. However, involvement of lymph nodes, spleen, or bone marrow is uncommon. Morphologically, there are three patterns of cutaneous involvement: epidermotropic, dermal, and subcutaneous. Often, more than one pattern may co-exist in a single biopsy specimen, or may be present in different biopsy specimens from the same patient. The lymphocytic infiltrate is composed of medium- to large-sized lymphocytes expressing CD56. Most cases lack both CD4 and CD8, although CD8 may be present in some cases. This group of lymphomas includes cases previously known as subcutaneous panniculitis-like T-cell lymphoma with a gamma/delta phenotype.
Cutaneous melanoma with no evidence of distant metastasis. (from AJCC 6th Ed.)
Cutaneous melanoma with metastases to all other visceral sites associated with normal serum lactate dehydrogenase (LDH) or distant metastases to any site associated with an elevated serum LDH. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma in which the status of distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Cutaneous melanoma without involvement of regional lymph nodes. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma involving four or more regional lymph nodes, or with a finding of matted metastatic nodes, or with in-transit metastasis or satellite(s) with metastasis in regional lymph node(s). (from AJCC 6th and 7th Eds.)
Cutaneous melanoma with no evidence of primary tumor. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma 1.01 to 2 mm in thickness, with or without ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma 1.01 to 2 mm in thickness, with no ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma 1.01 to 2 mm thick, with ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma 2.01 to 4 mm thick, with or without ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma 2.01 to 4 mm in thickness, with no ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma 2.01 to 4 mm thick, with ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma greater than 4.0 mm in thickness, with or without ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma greater than 4.0 mm in thickness, without ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma greater than 4.0 mm in thickness, with ulceration. (from AJCC 6th and 7th Eds.)
Cutaneous melanoma in situ. (from AJCC 6th and 7th Eds.)
A morphologic finding indicating the presence of cystic structures in a tissue sample.
Any interaction between a cognate ligand and any of a series of cytokine receptors. Activation of cytokine receptors is involved in regulation of the immune system, cell proliferation, cell death, as well as other multicellular processes.
A point mutation involving the substitution of Adenosine (a purine base) for Cytosine (a pyrimidine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A point mutation involving the substitution of Guanosine (a purine base) for Cytosine (a pyrimidine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A point mutation involving the substitution of Thymidine (a pyrimidine base) for Cytosine (a pyrimidine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
Decreased area under the plot of plasma concentration of a concomitant drug against time after its administration.
Decreased period of time required for the concentration or amount of a concomitant drug in the body to be reduced to exactly one-half of a given concentration or amount.
Decreased maximum (peak) concentration of a concomitant drug observed after its administration.
Decreased area under the plot of plasma concentration of a drug against time after drug administration.
Decreased maximum (peak) concentration of a drug observed after its administration.
Decreased time following concomitant drug administration at which the peak drug blood concentration occurs.
Decreased time following drug administration at which the peak drug blood concentration occurs.
A rare prolactin producing pituitary gland adenoma composed of acidophilic cells with many large secretory granules. The endoplasmic reticulum is not as abundant as in the sparsely granulated subtype.
A growth hormone producing pituitary gland adenoma composed of medium-sized acidophilic cells with granular cytoplasm and abundant secretory granules.
A symptom complex characterized by nervousness, chest pain, back pain, palpations, pruritus, and other usually mild symptoms occurring minutes following the initiation of dialysis with a new dialyzer.
A header term that includes the following diffuse large B-cell lymphoma subtypes by gene expression profiling: activated B-cell-like diffuse large B-cell lymphoma, germinal center B-cell-like diffuse large B-cell lymphoma, and type 3 diffuse large B-cell lymphoma.
Lymphangiomatosis diffusely involving the lung parenchyma.
Infection produced by direct contact with another person.
A morphologic finding indicating the presence of dysplastic epithelial changes in a large intestinal tissue sample that is affected by ulcerative colitis.
A synthetic peptide derived from the protein ESW/FLI1 type 1 with potential use in cancer immunotherapy. EWS/FLI1 is a fusion protein frequently found in patients with Ewing's sarcoma or primitive neuroectodermal tumors (PNET). Vaccination with EF-1 peptide may stimulate the host immune response to elicit a cytotoxic T-cell response against tumor cells that express this EWS/FL1 type 1 fusion protein.
A synthetic peptide derived from the protein ESW/FLI1 type 2 with potential use in cancer immunotherapy. EWS/FLI1 is a fusion protein frequently found in patients with Ewing's sarcoma or primitive neuroectodermal tumors (PNET). Vaccination with EF-2 peptide may stimulate the host immune response to elicit a cytotoxic T-cell response against tumor cells that express this EWS/FL1 type 2 fusion protein.
A nanoparticle-based formulation composed of a non-viral plasmid DNA vector encoding the human pro-inflammatory cytokine interleukin-12 (IL-12) encapsulated in a biodegradable, biocompatible lipoplex composed of polyethylene glycol (PEG), polyethylenimine (PEI), and cholesterol, with potential immunoactivating and antineoplastic activities. Upon intraperitoneal (IP) delivery of the PEG-PEI-cholesterol lipopolymer-encased IL-12 DNA plasmid vector GEN-1, the lipoplex is endocytosed by nearby cells, and the plasmid DNA is transported into the nucleus, which leads to local expresssion of IL-12. In turn, the increased IL-12 production at the tumor site activates the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma (IFN-g) and promoting cytotoxic T-cell responses against tumor cells.
A clinical stage I or II non-Hodgkin lymphoma with at least one of the following risk factors: large mediastinal mass, extranodal spread, elevated erythrocyte sedimentation rate, involvement of at least three lymph node areas, and B symptoms.
An adenocarcinoma with eccrine differentiation arising from the sweat glands. It includes the following subtypes: ductal eccrine adenocarcinoma, papillary eccrine carcinoma, and eccrine porocarcinoma.
Very small, round vesicles containing fluid and cellular debris observed on the surface of the cornea under slit-lamp examination in some types of corneal dystrophy and in wearers of extended-wear lenses.
A normal feature of responses to infectious agents that allows recognition of multiple antigenic targets, Epitope Spreading involves non-cross-reactive epitopes, distinct from the inducing epitope, becoming major targets of an ongoing immune response. Epitope spreading (ES) involves an increased presentation of cryptic epitopes on one protein (intermolecular ES) or dominant epitopes on neighboring molecules (intramolecular ES). The result is an increase in antibody repertoire diversify, resulting in an enhanced overall immune response. Conversely, epitope spreading is the primary immunopathogenic event in autoimmune diseases.
A rare adenoma of the adrenal cortex that produces estrogens. Male patients may develop gynecomastia and impotence.
A benign exophytic papillary neoplasm with fibrovascular cores lined by epithelial cells. It arises from the lower anterior nasal septum. Clinical manifestations include nasal obstruction, epistaxis, and the presence of a mass.
A benign mesenchymal neoplasm that shows mature skeletal muscle differentiation.
A change in the nucleotide sequence of the FH gene.
A rare morphologic variant of lung adenocarcinoma characterized by the presence of glandular structures containing glycogen-rich cells forming tubules that resemble fetal lung tubules.
A pharmaceutical product that has undergone all stages of production and testing, including packaging in its final container and labelling.
A morphologic architectural pattern in which a cellular population is distributed in a localized or relatively uneven fashion throughout a specified tissue area; not diffuse.
Consisting of abnormally decreased sensitivity, particularly to touch in the foot or leg.
An intermediate grade well differentiated tumor with neuroendocrine differentiation that arises from the pancreas. It is characterized by the presence of a clinical syndrome that results from hormone hypersecretion.
A low or intermediate grade well differentiated tumor with neuroendocrine differentiation that arises from the pancreas. It is characterized by the presence of a clinical syndrome that results from hormone hypersecretion.
A type of skin lesion that is marked by ulcerations (breaks on the skin or surface of an organ) and necrosis (death of living tissue) and that usually has a bad smell. This kind of lesion may occur in many types of cancer, including breast cancer, melanoma, and squamous cell carcinoma, and especially in advanced disease.
A cell-based vaccine comprised of K562 cells transfected with the granulocyte macrophage-colony stimulating factor (GM-CSF) gene with potential immunopotentiating properties. Vaccination with GM-K562 cells may stimulate the host immune system to produce an antitumoral T-lymphocyte response, thereby inhibiting tumor growth. K562 cells are derived from the human erythroleukemia cell line K562. GM-CSF (also known as sagramostim) expressed by vaccine cells binds to specific cell surface receptors, modulating the proliferation and differentiation of a variety of hematopoietic progenitor cells with some specificity towards stimulation of leukocyte production. GM-CSF also promotes antigen presentation, up-regulates antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function; it may also augment host antitumoral immunity.
The sodium salt of imetelstat, a synthetic lipid-conjugated, 13-mer oligonucleotide N3' P5'-thio-phosphoramidate with potential antineoplastic activity. Complementary to the template region of telomerase RNA (hTR), imetelstat acts as a competitive enzyme inhibitor that binds and blocks the active site of the enzyme (a ""telomerase template antagonist""), a mechanism of action which differs from that for the antisense oligonucleotide-mediated inhibition of telomerase activity through telomerase mRNA binding. Inhibition of telomerase activity in tumor cells by imetelstat results in telomere shortening, which leads to cell cycle arrest or apoptosis.
An adenocarcinoma that arises from the gallbladder. It is characterized by the presence of neoplastic tubular glands lined by columnar cells or neoplastic glands lined by goblet cells.
A rare morphologic variant of gallbladder adenocarcinoma composed of malignant glandular epithelium with a predominance of glycogen rich clear cells. The cells display hyperchromic nuclei and well-defined cytoplasmic borders.
Biliary intraepithelial neoplasia that affects the gallbladder epithelium. It is characterized by the absence of intraluminal micropapillary projections.
A neoplastic, non-invasive lesion that affects the gallbladder epithelium. It is characterized by the presence of atypical epithelial cells with an increased nuclear/cytoplasmic ratio, nuclear hyperchromasia, and loss of nuclear polarity.
An adenoma that arises from the gallbladder. It is characterized by the presence of a papillary growth pattern.
Biliary intraepithelial neoplasia that affects the gallbladder epithelium. It is characterized by the presence of intraluminal micropapillary projections.
An adenoma that arises from the gallbladder. It is characterized by the presence of a tubular growth pattern.
An adenoma that arises from the gallbladder. It is characterized by the presence of tubular and papillary growth patterns.
An uncommon, poorly circumscribed, benign neoplasm arising in the soft tissues of infants, children and adolescents. It is characterized by the presence of haphazardly arranged spindle-shaped fibroblasts, collagenous stroma formation, and plaque-like growth pattern. There is a strong genetic component associating the neoplasm with Gardners syndrome and deep fibromatosis/desmoid tumor.
A benign or malignant granular cell tumor that arises from the stomach.
A benign, intermediate, or malignant mesenchymal neoplasm that arises from the stomach.
An adenoma of the anterior lobe of the pituitary gland that produces gonadotrophic hormones (FSH and/or LH) or shows evidence towards gonadotroph differentiation. The majority of cases are hormonally non-functional. Clinical manifestations include visual disturbances, hypopituitarism, headache, and acute hemorrhagic necrosis of the pituitary gland.
A change in the nucleotide sequence of the GNAS gene.
A point mutation involving the substitution of Adenosine (a purine base) for Guanosine (a purine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A point mutation involving the substitution of Cytosine (a pyrimidine base) for Guanosine (a purine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A point mutation involving the substitution of Thymidine (a pyrimidine base) for Guanosine (a purine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A vaccine comprised of HER-2-neu and carcinoembryonic antigen synthetic (CEA) peptides, combined with the adjuvants granulocyte-macrophage colony stimulating factor (GM-CSF), and Montanide ISA-51 with potential antineoplastic activity. HER-2-neu, CEA peptides, GM-CSF, Montanide ISA-51 vaccine may stimulate a cytotoxic T-cell response against HER-2-neu- and CEA-expressing tumor cells. The GM-CSF adjuvant stimulates the proliferation of monocytes and monocyte differentiation into macrophages and dendritic cells, immunohematopoietic elements with important antitumoral functions. Montanide ISA-51, also known as incomplete Freund's adjuvant or IFA, is a stabilized water-in-oil emulsion adjuvant containing mineral oil with mannide oleate added as a surfactant that non-specifically stimulates cell-mediated immune responses to antigens.
T cells specific for the human epidermal growth factor receptor 2 (HER2) with potential immunopotentiating activity. T cells directed against HER2, overexpressed on many tumor cells, are collected from HER2-expressing tumor tissue, expanded ex vivo and, then re-introduced in the patient. Re-introduction of ex vivo-expanded HER2-specific T cells may enhance the cytotoxic T cell response against tumor cells overexpressing HER2, resulting in inhibition of tumor growth.
A neoplastic process characterized by a diffuse poorly circumscribed overgrowth of adipose tissue in the breast and cervical areas, and an accumulation of visceral fat. It is associated with antiretroviral therapy. Clinical presentation includes hyperlipidemia, insulin resistance, and fat atrophy of the face and limbs.
A peptide vaccine comprised of synthetic HLA-A1, -A2 and -B35 restricted survivin epitopes combined with the adjuvant Montanide ISA-51 with potential antineoplastic activity. Upon administration, HLA-A1, A2, B35-restricted survivin peptides/Montanide ISA-51 vaccine may stimulate a cytotoxic T cell response against tumor cells that overexpress survivin, resulting in tumor cell lysis. Montanide ISA-51, also known as incomplete Freund's adjuvant or IFA, is a stabilized water-in-oil emulsion adjuvant containing mineral oil with mannide oleate added as a surfactant that non-specifically stimulates cell-mediated immune responses to antigens.
A peptide comprised of the synthetic human leukocyte antigen (HLA)-B44-binding peptides derived from amino acid sequences of MAGE-3 with potential antitumor activity. Vaccination with HLA-B44-restricted MAGE-3 peptide may elicit a cytotoxic T lymphocyte immune response against tumor cells expressing MAGE-3. MAGE-3 is an antigen found on many tumor cell types, including melanoma and lung, prostate, colon, thyroid, and breast cancers.
A synthetic peptide consisting of synthetic human leukocyte antigen (HLA)-B44-binding peptides derived from amino acid sequences of the melanoma-associated enzyme tyrosinase with potential antitumor activity. Vaccination with HLA-B44-restricted tyrosinase peptide may stimulate cytotoxic T lymphocyte response against tyrosinase-expressing tumor cells, resulting in decreased tumor growth and cell lysis.
A second generation synthetic oligonucleotide with immunomodulatory and potential antineoplastic activities. HYB2055 consists of unmethylated CpG dinucleotide motifs that are present abundantly in bacterial and parasitic DNA, and a novel DNA structure, called an immunomer that contributes to metabolic stability of the agent. Upon infections, CpG-containing DNA released from pathogenic organisms triggers host immune responses, which are mediated by the action of intracellular toll-like receptor 9 (TLR9), a pattern recognition receptor. This agent mimics bacterial DNA and selectively activates TLR9, thereby initiating immune signaling pathways, and leading to activation of B-cells and dendritic cells and induction of Th1-type cytokine production.
A non-malignant, focal growth in the heart, composed of unencapsulated nodules of enlarged, hypertrophic, mature cardiac myocytes with a variable amount of collagen and fat.
An analog of the sponge-derived anti-microtubule tripeptide hemiasterlin with antimitotic and potential antineoplastic activities. Hemiasterlin analog E7974 binds to the Vinca domain on tubulin, resulting in inhibition of tubulin polymerization and microtubule assembly; depolymerization of existing microtubules; inhibition of mitosis; and inhibition of cellular proliferation. This agent may have more affinity for the beta-3 tubulin isotype.
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant susceptibility for diffuse gastric cancer, a poorly differentiated adenocarcinoma that infiltrates into the stomach wall causing thickening of the wall (linitis plastica) without forming a distinct mass. Diffuse gastric cancer is also referred to as signet ring carcinoma or isolated cell-type carcinoma. The average age of onset of HDGC is 38 years (range: 14-69 years). The majority of the cancers in individuals with a CDH1 pathogenic variant occur before age 40 years. The estimated cumulative risk of gastric cancer by age 80 years is 70% for men and 56% for women. Women are also at a 42% risk for lobular breast cancer.
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is characterized by cutaneous leiomyomata (multiple or single in 76% of affected individuals), uterine leiomyomata (fibroids), and/or a single renal tumor. Cutaneous leiomyomata appear as skin-colored to light brown papules or nodules distributed over the trunk and extremities, and occasionally on the face, and appear at a mean age of 25 years, increasing in size and number with age. Uterine leiomyomata are present in almost all females with HLRCC and tend to be numerous and large; age at diagnosis ranges from 18 to 52 years, with most women experiencing irregular or heavy menstruation and pelvic pain. Renal tumors causing hematuria, lower back pain, and a palpable mass are usually unilateral, solitary, and aggressive and range from type 2 papillary to tubulo-papillary to collecting-duct carcinomas. They occur in about 10%-16% of individuals with HLRCC; the median age of detection is 44 years.
A pathologic process inherited in a familial pattern.
A morphologic finding indicating the presence of tissues that do not normally occur in the specific anatomic site or are found admixed with a neoplastic cellular infiltrate of a different cellular origin.
A rare benign slow growing adipose tumor, characterized by the presence of polygonal brown fat cells with abundant cytoplasm, that arises within the nervous system.
A high grade malignant neoplasm that arises from the lung and is characterized by the presence of malignant neuroendocrine cells. This category includes small cell lung carcinoma, large cell lung neuroendocrine carcinoma, and combined lung carcinoma.
Histiocytoid cardiomyopathy, which was initially described by Voth (1962), goes by various names, including infantile xanthomatous cardiomyopathy (MacMahon, 1971), focal lipid cardiomyopathy (Bove and Schwartz, 1973), oncocytic cardiomyopathy (Silver et al., 1980), infantile cardiomyopathy with histiocytoid change (Ferrans et al., 1976), and foamy myocardial transformation of infancy (Yatani et al., 1988). The disorder is a rare but distinctive entity of infancy and childhood characterized by the presence of characteristic pale granular foamy histiocyte-like cells within the myocardium. It usually affects children younger than 2 years of age, with a clear predominance of females over males. Infants present with dysrhythmia or cardiac arrest, and the clinical course is usually fulminant, sometimes simulating sudden infant death syndrome (Andreu et al., 2000).
A patient condition where evaluation and/or treatment in a hospital is considered mandatory.
Growth of tissue in or around a foreign body as the body's antibody response to the foreign body.
A rare, EBV-positive cutaneous T-cell lymphoproliferative disorder, composed of CD8 positive cytotoxic T-lymphocytes. It affects children, almost exclusively in Latin America and Asia. Patients present with papulovesicular skin lesions, clinically resembling hydroa vacciniforme, in areas of sun-exposed skin.
A tumor characterized by the presence of mature ganglion cells and neuronal differentiation, arising in the hypothalamus. It is often associated with the presence of pituitary gland adenomas. Symptoms include acromegaly and precocious puberty.
A small-molecule inhibitor of heat shock protein 90 (HSP90) with antiproliferative and antineoplastic activity. IPI-504 binds to and inhibits the cytosolic chaperone functions of HSP90, which maintains the stability and functional shape of many oncogenic signaling proteins and may be overexpressed or overactive in tumor cells. IPI-504-mediated inhibition of HSP90 promotes the proteasomal degradation of oncogenic signaling proteins in susceptible tumor cell populations, which may result in the induction of apoptosis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=437784&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=437784&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48401"" NCI Thesaurus)
An increased number of myeloid precursors in the bone marrow.
Insufficient structural and functional connection between living bone and the surface of a synthetic implant.
Increased area under the plot of plasma concentration of a concomitant drug against time after its administration.
Increased period of time required for the concentration or amount of a concomitant drug in the body to be reduced to exactly one-half of a given concentration or amount.
Increased maximum (peak) concentration of a concomitant drug observed after its administration.
Increased area under the plot of plasma concentration of a drug against time after drug administration.
Increased maximum (peak) concentration of a drug observed after its administration.
Increased time following concomitant drug administration at which the peak drug blood concentration occurs.
Infection transmitted by water, food or other means of conveyance.
A cataract that has been produced artificially or by induction, e.g. as a result of device use, medication, trauma, tears, falls, accidental injury, etc.
Inhibition of Amyloidogenesis is a process that prevents the formation or growth of amyloid structures.
Insulin that has been modified to contain an ASPARTIC ACID instead of a PROLINE at position 38 of the B-chain.
An intermediate grade malignant neoplasm with neuroendocrine differentiation that arises from the lung. This category includes atypical carcinoid tumor.
A borderline blood vessel neoplasm that has locally aggressive behavior.
A borderline blood vessel neoplasm that may metastasize on rare occasions.
A patient condition when action or ministration whose purpose is to improve health or to alter the course of a disease is considered essential and mandatory in order to prevent permanent impairment or damage.
A dissection of an artery that occurs though a tear in the inner lining of the blood vessel.
A malignant neoplasm arising from the large blood vessels. It is characterized by the presence of tumor cells that grow within the lumen of the blood vessels. The intraluminal tumor growth may result in vascular obstruction and spread of tumor emboli to peripheral organs. The prognosis is usually poor.
Increased pressure of the intraocular fluid in the eye.
An epithelial neoplasm that arises from ectopic thymic tissue in the lung. Histologically it is identical to the thymomas that arise from the mediastinum. Signs and symptoms include cough, dyspnea, fever, and weight loss. Surgical excision is the recommended treatment.
The entry of a cell or foreign substance into a blood or lymphatic vessel. This process is pertinent to the description of the entry of cancer cells into a vessel, and the initiation of metastasis.
A melanoma of the skin that is not confined to the dermal-epidermal junction, and has infiltrated the dermis.
A carcinoma that is not confined to the prostatic epithelium but has spread to the surrounding stroma of the prostate gland. The vast majority of invasive prostate carcinomas are adenocarcinomas.
A radioimmunoconjugate comprised of the chimeric monoclonal antibody G250 conjugated with the positron emitter iodine I 124. The antibody moiety of iodine I 124 chimeric monoclonal antibody G250 may bind to renal cell carcinoma (RCC) cells that express the RCC-associated antigen G250, allowing detection of tumor-localized iodine I 124 with positron emission tomography (PET). G250 is a cell surface tumor-associated antigen (TAA) that is found in the majority of renal cell carcinomas.
A squamous cell carcinoma that arises from the head and neck region and is characterized by prominent production of keratin.
A squamous cell carcinoma that arises from the paranasal sinuses and is characterized by prominent production of keratin.
A benign uni- or multicystic, intraosseous tumor of odontogenic origin, with a characteristic lining of parakeratinized stratified squamous epithelium and potential for aggressive, infiltrative behaviour.
Having an appearance of thin plate-like structures.
A prolonged-release depot suspension of microparticles containing the acetate salt of lanreotide, a synthetic peptide analog of the naturally occurring somatostatin, and copolymers. Lanreotide inhibits the secretion of growth hormone (GH) by binding to pituitary somatostatin receptors, and may inhibit various other hormones, including thyroid-stimulating hormone (TSH) and the gastroenteropancreatic hormones insulin, glucagon and gastrin. This agent has a much longer duration of action than natural somatostatin and is selective towards the inhibition of growth hormone.
A rare variant of squamous cell carcinoma that arises from the larynx. It is characterized by acantholysis of the tumor cells that results in the formation of pseudolumina that resemble glandular structures.
A rare, aggressive carcinoma that arises from the larynx. It is characterized by the presence of squamous cell carcinoma and adenocarcinoma components. Hoarseness, sore throat, and dysphagia are the presenting symptoms.
An aggressive variant of squamous cell carcinoma that arises from the pyriform sinus or supraglottic area. It is characterized by the presence of small malignant cells with hyperchromatic nuclei and scant amount of cytoplasm forming lobules with peripheral palisading. Comedonecrosis may be present. An in situ or invasive keratinizing squamous cell carcinoma component is always present. Signs and symptoms include hoarseness, dysphagia, pain, and neck mass.
A rare and aggressive carcinoma that arises from the larynx. It is characterized by the presence of an undifferentiated carcinoma accompanied by a prominent reactive lymphoplasmacytic infiltrate.
A carcinoma that arises from the larynx and is characterized by the presence of a malignant spindle cell cellular component and a squamous cell carcinoma component. The latter is either in situ or invasive squamous cell carcinoma.
The disturbance of a cusp of a heart valve, often resutling in dysfunction of the valve.
The disturbance of a cusp of a heart valve secondary to the accumulation of calcium on the valve tissue. This most often results in stenosis of the valve.
The disturbance of a cusp of a heart valve secondary to an increase in tissue mass at the valve site, which can lead to valve dysfunction. This often happens as a result of fibrosis of tissue surrounding the suture line of a prosthetic valve.
The disturbance of a cusp of a heart valve secondary to infection affecting the valve tissue, which can result in valvular dysfunction.
The disturbance of a cusp of a heart valve secondary to irritation by surgical sutures, which can result in valvular dysfunction.
The disturbance of a cusp of a heart valve without an identifiable cause.
A term referring to the number of anatomic sites affected by a disease.
A localized neoplasm of probable fibroblastic derivation, that arises from the pericardium. It is characterized by the presence of round to spindle-shaped cells, hylanized stroma formation, thin-walled branching blood vessels, and thin bands of collagen.
A localized hepatocellular carcinoma that occurs during adulthood and it is amenable to surgical resection.
A localized hepatocellular carcinoma that occurs during adulthood and it is not amenable to surgical resection.
A finding that the flexibility of a joint is below the expected range of normal for that individual.
A well differentiated mucinous adenocarcinoma that arises from the appendix. It is characterized by slow growth and it is associated with the development of pseudomyxoma peritonei. Unlike the high grade mucinous adenocarcinoma of the appendix, it usually does not spread beyond the peritoneum and it does not metastasize to distant anatomic sites.
A low grade fibromyxoid sarcoma characterized by the presence of prominent collagen rosettes.
A low grade malignant neoplasm with neuroendocrine differentiation that arises from the lung. This category includes typical carcinoid tumor.
A low grade malignant neoplasm arising from the deep soft tissues. It is characterized by the presence of spindle-shaped myofibroblasts and collagenous stroma formation in a storiform growth pattern. Metastasis is very rare.
The most frequently seen morphologic variant of lung adenocarcinoma characterized by a mixture of architectural patterns, including acinar, papillary, bronchioloalveolar, and solid pattern.
A carcinoid tumor of the lung showing focal necrotic changes or a number of mitotic figures between 2 and 10/10 high power fields.
A biphasic synovial sarcoma arising from the lungs.
A benign neoplasm composed of hyaline cartilage arising from the lung. It is characterized by the presence of chondrocytes, a lobulated growth pattern, and calcification.
A well differentiated morphologic variant of lung adenocarcinoma characterized by the predominance of clear cells.
A lung carcinoma arising within the bronchi or bronchial tubes. It is characterized by the presence of myoepithelial cells, spindle cells, clear cells, and duct-forming epithelial cells. Surgical resection may be curative.
A germ cell tumor that arises from the lung.
A benign papillary neoplasm that arises endobronchially. It is characterized by the presence of fibrovascular cores lined by columnar, cuboidal, and goblet cells. Patients usually present with signs and symptoms of bronchial obstruction. Complete resection is curative.
A rare malignant neoplasm that derives from melanocytes and arises from the lung in a patient with no history of previous melanoma and no evidence of melanoma in another site at the time of diagnosis. It usually presents as a solitary lesion and the prognosis is poor.
An exceedingly rare benign endobronchial neoplasm characterized by the presence of fibrovascular cores which are lined by both squamous and glandular epithelium. Patients present with obstructive symptoms. Complete resection is curative.
A monophasic synovial sarcoma arising from the lungs.
A morphologic variant of lung adenocarcinoma characterized by the presence of mucin pools containing islands of well differentiated adenocarcinoma cells.
A very rare, well circumscribed, benign cystic neoplasm that arises from the lung. It is characterized by the presence of cysts which are lined by tall mucinous epithelium and filled with mucin.
A lung carcinoma characterized by the presence of malignant non-keratinizing squamoid cells, mucin-producing cells and intermediate type cells.
A very rare, well circumscribed, benign epithelial neoplasm that arises from the bronchus. It is characterized by the presence of epithelial cells, myoepithelial cells, and fibromyxoid stroma.
A rare, aggressive, poorly differentiated, non-small cell lung carcinoma characterized by the presence of a sarcomatoid component often associated with giant cell differentiation. There is a male to female ratio of 4:1. Clinical symptoms include cough, hemoptysis, chest pain, progressive dyspnea and fever secondary to recurrent pneumonia. Cigarette smoking is a major risk factor.
A morphologic variant of lung adenocarcinoma characterized by the presence of signet ring cells.
A benign, intermediate, or malignant mesenchymal neoplasm that arises from the lung.
A morphologic variant of sarcomatoid carcinoma characterized by the presence of malignant spindle cells and focal lymphoplasmacytic infiltrates. Adenocarcinoma cells, malignant squamous cells, and giant cells are not present.
A papillary neoplasm that arises endobronchially. It is characterized by the presence of a delicate fibrovascular core lined by stratified squamous epithelium. Squamous cell papillomas can be solitary or multiple. Patients usually present with signs and symptoms of bronchial obstruction. Because of the possibility of recurrence and reported cases of squamous cell carcinomas arising at the excision site of squamous cell papillomas, complete excision is indicated.
A synovial sarcoma arising from the lungs.
A carcinoid tumor of the lung characterized by the absence of necrosis and the presence of less than 2 mitoses per 10 high power fields.
A term referring to the presence of tumor emboli or tumor masses within lymphatic vessels.
A rare and distinctive type of lung carcinoma characterized by the presence of a syncytial growth pattern, large vesicular nuclei with eosinophilic nucleoli, and dense lymphoplasmacytic infiltration.
A synthetic small molecule with potential antineoplastic activity. MK0731 selectively inhibits kinesin spindle protein (KSP), which may result in the inhibition of mitotic spindle assembly, induction of cell cycle arrest during the mitotic phase, and apoptosis in tumor cells that overexpress KSP.
A synthetic small molecule with potential antineoplastic activity. MK0752 inhibits the Notch signaling pathway, which may result in induction of growth arrest and apoptosis in tumor cells in which the Notch signaling pathway is overactivated. The Notch signaling pathway plays an important role in cell-fate determination, cell survival, and cell proliferation.
Expression of a fusion protein that results from a translocation involving the human MOZ gene and various fusion gene partners. The fusion transcript is the result of the translocation of genetic material from any one of several chromosomes to the 8p11 region. This fusion protein is associated with acute myeloid leukemia.
CD34+ peripheral blood stem cells (PBSC) isolated from patient with hematopoietic cell tumor, and transfected with murine stem cell virus retroviral vector encoding a mutant version of the human DNA repair protein O6-alkylguanine-DNA methyltransferase (MGMT). This mutant MGMT protein, MGMTP140K, is resistant to the O6-benzylguanine (BG), an inhibitor of the wild type MGMT. Introduction of these transfected autologous PBSCs back to the patient, may stimulate the expression of the O6 BG resistant mutant MGMT protein, which when used in combination with O6-alkylating drugs could protect the hematopoietic system against the hematopoietic toxicity of chemotherapeutic agents.
A radioimaging agent consisting of the 131 I-labeled murine monoclonal antibody 791T/36 which is directed against the tumor-associated antigen 791Tgp72. M A 131I Osteogenic Sarcoma binds to an antigen found in osteogenic sarcomas and colorectal and breast carcinomas, thereby enabling the scintigraphic visualization of primary and metastatic tumors that express 791Tgp72. (NCI04)
A monoclonal antibody, subtype IgG2a, that targets lactate dehydrogenase (LDH) with potential use in cancer immunotherapy and immunodiagnostics. Isoforms of LDH are recognized by the immune systems of patients with breast cancer, indicating that these antigens may be expressed by breast cancer cells. Consequently, M A idiotypic determinants may have utility in the immunodiagnosis or immunotherapy of certain types of cancer. (NCI04)
A radiolabeled monoclonal antibody directed against an antigen expressed by breast cancer cells with potential use in cancer immunodiagnostics and immunotherapy. (NCI04)
A radiolabeled monoclonal antibody (also known as B72.3) directed against the tumor-associated glycoprotein (TAG)-72 with potential use in cancer radioimmunodiagnostics, radioimmunoscintigraphy, and radioimmunoguided surgery (RIGS). (TAG)-72 is an antigen that may be expressed by breast, colorectal, and ovarian carcinomas. (NCI04)
A radiolabeled murine monoclonal antibody (also known as T101) directed against T65, an antigen found on cutaneous T cell lymphoma (CTCL) cells and chronic lymphocytic leukemia (CLL) cells as well as normal T lymphocytes. T101 labeled with 131I, 125I, or 111In has potential use in the radioimaging of CTCL. M A radiolabeled T101 human T-lymph may induce a cytotoxic T-cell response against T65-expressing T cells. (NCI04)
A morphologic variant of papillary carcinoma of the thyroid gland characterized by the predominance or the exclusive presence of macrofollicles. Some of the malignant follicular cells display the nuclear features that characterize the papillary adenocarcinomas of the thyroid gland.
A germ cell tumor that affects the central nervous system, characterized by the presence of malignant morphologic characteristics. Representative examples include choriocarcinoma, embryonal carcinoma, and germinoma.
A neoplasm that arises from the hair follicle and metastasizes to other anatomic sites.
A primary or metastatic malignant neoplasm that affects the lung and pleura.
Malignant neoplasm involving the accessory urethral glands
A pituitary gland adenoma composed of acidophilic cells that produce both growth hormone and prolactin. Immunohistochemical studies reveal the presence of these two hormones localized in the same cell.
Lymph nodes adherent to each other, usually a result of tumor spread.
A rare extragonadal germ cell tumor that arises from the mediastinum and is associated with the presence of a somatic-type malignant component. The somatic malignancy is usually a sarcoma (e.g., embryonal rhabdomyosarcoma, angiosarcoma, or leiomyosarcoma), adenocarcinoma, squamous cell carcinoma, adenosquamous carcinoma, or primitive neuroectodermal tumor. The prognosis is poor.
An extragonadal non-seminomatous malignant germ cell tumor that arises from the mediastinum and is associated with a hematologic malignancy. The hematologic malignancies are clonally related to the malignant germ cell tumor and include acute leukemias, myelodysplastic syndromes, myeloproliferative neoplasms, and mastocytosis.
A mass-forming malignant neoplasm that arises from the mediastinum and is characterized by the proliferation of myeloblasts or immature myeloid cells. It may present in association with or precede acute myeloid leukemia, or it may be the first manifestation of relapse of acute myeloid leukemia.
A benign or malignant extra-adrenal parasympathetic paraganglioma that arises from paraganglia in the mediastinum. Clinical signs and symptoms include chest pain, cough, hoarseness, and dysphagia.
A precursor T-lymphoblastic lymphoma that arises from the mediastinum. It usually presents with an anterior mediastinal mass and respiratory distress. It may present acutely with superior vena cava syndrome. It usually affects adolescent and young adult males. It is treated with aggressive chemotherapy and radiation. The prognosis is better in the pediatric patients.
A precursor T-cell lymphoid neoplasm composed of small to medium-sized lymphoblasts that affects the mediastinum.
A localized neoplasm of probable fibroblastic derivation, that arises from the mediastinum. It is characterized by the presence of round to spindle-shaped cells, hylanized stroma formation, thin-walled branching blood vessels, and thin bands of collagen.
An invasive or non-invasive thymoma that arises from the mediastinum. Thymomas are the most common anterior mediastinal tumors.
Tumor infiltrating lymphocytes (TIL) harvested directly from infiltrate of a patient's melanoma and cultured with interleukin-2 to expand the TIL cell population. Tumor infiltrating lymphocytes have specific activity against the melanoma from which they are derived. Introducing these melanoma tumor-reactive autologous tumor infiltrating lymphocytes back into the same patient may enhance a cytotoxic T-cell-mediated immune response against the melanoma cancer cells.
A morphologic variant of chondrosarcoma arising from the bone. It is characterized by the presence of malignant small round cells, biphasic growth pattern, and well differentiated hyaline cartilage. Clinical presentation includes pain and swelling. The clinical course is aggressive, with local recurrences and distant metastases.
A rare type of well circumscribed or encapsulated thymoma with a biphasic architecture, consisting of epithelial cell islands and bundles of spindle cells. The vast majority of reported cases had a benign clinical course.
An extraskeletal myxoid chondrosarcoma which has spread to another anatomic site.
A pheochromocytoma that has metastasized to other anatomic sites.
A finding of microcalcifications located within neoplastic tissue.
A finding of microcalcifications located within neoplastic tissue, and in tissues without neoplasm.
A rare type of thymoma characterized by the presence of multiple, well formed epithelial nodules separated by a lymphocytic stroma that usually contains germinal centers. Reported cases have not been associated with recurrences or metastases.
A rare type of thymoma, composed of multifocal epithelial proliferations less than 1 mm in diameter. This type of thymoma usually occurs in myasthenia gravis patients without any macroscopic (gross) evidence of tumor.
A thymoma that focally infiltrates the surrounding capsule and invades the mediastinal fat. This type of thymoma is usually recognized only after microscopic examination. Grossly, it appears indistinguishable from encapsulated thymoma.
A dose of medicine that was not taken at the prescribed dosing interval.
A change in the nucleotide sequence of any gene that encodes one of the proteins in the succinate dehydrogenase (SDH) complex.
A rare carcinoma with a poor prognosis, characterized by the presence of a mixture of exocrine and neuroendocrine malignant epithelial cells in both the pancreas and metastatic sites. Symptoms include jaundice, abdominal pain, and weight loss.
Point mutations at various locations in a DNA sequence from eukaryotic or prokaryotic organisms in which a nucleotide substitution, deletion or insertion has occurred at each affected site. These abnormalities can be either heritable or occur somatically.
An infrequent pituitary gland adenoma composed of an admixture of acidophilic and chromophobic cells that produce growth hormone and prolactin respectively. Unlike mammosomatotroph adenomas, these two hormones are not localized in the same cell by immunohistochemistry.
A rhabdomyosarcoma composed of embryonic and alveolar components. It is characterized by the presence of spindle cells with myoblastic differentiation, a myxoid stroma, and fibrous septa. These tumors were previously considered variants of alveolar rhabdomyosarcoma. The lack of PAX3-FOXO1 fusions in most of these tumors suggests that are biologically and clinically related to embryonal rhabdomyosarcoma.
A monoclonal antibody directed against the B-cell surface antigen CD40 with potential antineoplastic activity. Monoclonal antibody CHIR-12.12 binds to and inhibits CD40, thereby inhibiting CD40 ligand-induced cell proliferation and triggering cell lysis via antibody-dependent cellular cytotoxicity (ADCC) in cells overexpressing CD40. CD40, an integral membrane protein found on the surface of B lymphocytes, is a member of the tumor necrosis factor receptor superfamily and is highly expressed in a number of B-cell malignancies. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=432936&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=432936&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48405"" NCI Thesaurus)
A chromosomal abnormality consisting of the absence of a copy (homolog) of chromosome 3.
A morphologic finding indicating the presence of more than five mitotic figures per fifty high power fields in a cellular infiltrate.
A vaccine consisting of a plasmid DNA encoding the murine prostate-specific membrane antigen (PSMA). Upon administration, expressed PSMA may stimulate a cytotoxic T cell response against tumor cells that express PSMA, resulting in tumor cell lysis. (NCI05)
A vaccine consisting of a plasmid DNA encoding the murine melanoma-associated antigen gp100. Upon administration, expressed gp100 antigen may stimulate a cytotoxic T cell HLA-A2.1-restricted immune response against tumor cells that express the gp100 antigen, resulting in tumor cell lysis. (NCI05)
A multicystic lesion that arises from the epithelial component of the thymus gland. It is usually associated with the presence of lymphoid follicles and degenerative changes. Although its etiology is unknown, it has been described in patients with HIV infection and in patients with nodular sclerosis Hodgkin lymphoma affecting the thymus gland.
Point mutations at various locations in a DNA sequence from either a eukaryotic or prokaryotic organism that causes a base change which results in an amino acid change in the protein product. This alteration may affect the stability and/or activity of the protein. Multiple mutation abnormalities may be heritable or occur spontaneously.
Multiple point mutations in a DNA sequence from eukaryotic or prokaryotic organisms in which each mutation occurs by substitution of a purine base for a different purine base or a pyrimidine base for another pyrimidine base. These abnormalities can be either heritable or occur somatically.
Multiple point mutations in a DNA sequence from eukaryotic or prokaryotic organisms in which each mutation occurs by substitution of a purine base for a pyrimidine base or vice versa. These abnormalities can be either heritable or occur somatically.
An involuntary, compulsive, repetitive stereotyped movement, usually of the face or shoulders.
A morphologic finding that indicates the presence of myofibroblastic differentiation in a cellular infiltrate of a tissue sample.
A low grade, locally aggressive, fibroblastic neoplasm that occurs primarily in the distal extremities. It is characterized by the presence of spindle-shaped fibroblasts, multivacuolated lipoblast-like cells, bizarre ganglion-like cells with inclusion-like nuclei, myxoid stroma formation, and a mixture of acute and chronic inflammatory cells. Distant metastases are very rare.
A general term that refers to a TNM finding of cancer metastases usually in a limited number of regional lymph nodes. The definition of N1c TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases in 1 to 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected; for colorectal cancer it refers to tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional lymph node metastasis.
A general term that refers to a TNM finding of cancer metastases in multiple lymph nodes. The definition of N3a TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm) or metastases to the infraclavicular (level III axillary) lymph nodes; for gastric cancer it refers to metastases in 7-15 regional lymph nodes; for nasopharyngeal cancer it refers to metastases to one or more lymph nodes greater than 6 cm in greatest dimension.
A general term that refers to a TNM finding of cancer metastases in multiple lymph nodes. The definition of N3b TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases in clinically detected ipsilateral internal mammary lymph nodes in the presence of one or more positive axillary lymph nodes, or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected; for gastric cancer it refers to metastases in sixteen or more regional lymph nodes; for nasopharyngeal cancer it refers to extension to the supraclavicular fossa.
A general term that refers to a TNM finding of cancer metastases in multiple lymph nodes. The definition of N3c TNM finding depends on the specific type of cancer that it refers to; for example, for breast cancer it refers to metastases in ipsilateral supraclavicular lymph nodes.
A molecular genetic abnormality that refers to the mutation of the NF2 gene located at 22q12.2.
A nonkeratinizing nasopharyngeal carcinoma characterized by the presence of cells without prominent nucleoli, cellular stratification, and a lymphoplasmacytic infiltrate.
A benign or malignant extra-adrenal paraganglioma arising from the nasopharynx and nose. Epistaxis or nasal obstruction are common presenting symptoms.
Indicates the absence of tumor cells at the edge of a surgically excised specimen.
An abnormality that affects hearing within the first month after birth. It may or may not result in hearing loss.
A neoplastic process arising from the C-cells of the thyroid gland. It is considered a precursor of hereditary medullary thyroid gland carcinoma, and it is associated with mutations of the RET gene.
A morphological appearance characteristic of invasive carcinomas in which there is focal or extensive transformation (metaplasia) of nests of malignant epithelial cells into cells which resemble neurosecretory cells morphologically, immunohistochemically, and by electron microscopy.
A finding of pathologic function within the central or peripheral nervous system, secondary to developmental abnormalities, infections, neurologic damage, or tumors.
A desmoplastic melanoma characterized by the presence of nerve infiltration by atypical spindled melanocytes.
Diagnostic tests fail to detect presence of metastatic lesions.
An adenoma of the adrenal cortex characterized by the absence of a hormonal syndrome or symptoms suggestive of adrenal disease.
An intermediate grade well differentiated tumor with neuroendocrine differentiation that arises from the pancreas. It is characterized by the absence of a hormone-related clinical syndrome.
A pathologic process that is not inherited in a familial pattern.
A non-neoplastic disorder that affects the anus. Representative examples include hemorrhoids, ulcers, and infections.
Any disorder other than abnormal tissue growth resulting from uncontrolled cell proliferation.
A non-neoplastic disorder that affects the esophagus. Representative examples include infections, ulcers, and gastroesophageal reflux disease.
A non-neoplastic disorder that affects the liver parenchyma and the intrahepatic bile ducts. Representative examples include hepatitis, cirrhosis, and cholangitis.
A non-neoplastic disorder that affects the pancreas. Representative examples include pancreatitis and pancreatic insufficiency.
A non-neoplastic disorder that causes a disturbance in normal vision. Representative examples include amblyopia, astigmatism, myopia, and cataracts.
An expected natural death from a cardiac cause. This condition usually occurs in persons with pre-existing cardiac abnormalities or disease.
An indication that a subject has not agreed with or followed the instructions related to the study medication.
Cancer that is not dependent upon the presence of estrogen for metastasis or growth. 2005
One of the possible results of an adverse event outcome that indicates that the event has not improved or recuperated.
Nucleoside Analogue Incorporation involves assimilation of nucleoside or nucleotide analogues into DNA or RNA.
A non-functioning pituitary gland adenoma without hormonal immunoreactivity or evidence of specific adenohypophysial cell derivation.
A morphologic variant of papillary carcinoma of the thyroid gland characterized by the presence of papillary or follicular structures, containing malignant follicular cells with abundant granular eosinophilic cytoplasm. These cells have the nuclear features that characterize the papillary carcinomas of the thyroid gland.
A recombinant oncolytic adenovirus encoding the immunohematopoietic cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) with potential antineoplastic activity. Upon administration, the oncolytic adenovirus selectively infects and replicates in tumor cells, which may result in tumor cells lysis. Synergistically, GM-CSF (sargramostim) expressed by the oncolytic adenovirus may promote a cytotoxic T cell response against tumor cells harboring the oncolytic adenovirus, resulting in an immune-mediated tumor cell death.
A morphologic finding indicating the presence of bone elements in a tissue sample.
A benign, usually self-limited fibro-osseous lesion of the bone that affects infants and children. It usually arises from the cortical bone of the anterior mid-shaft of the tibia. Patients usually present with swelling or painless bowing of the tibia. Progression to adamantinoma has been reported in some cases.
The potassium salt form of oxaprozin and a member of the propionic acid group of non-steroidal anti-inflammatory drugs (NSAIDs) with anti-inflammatory, analgesic and antipyretic properties. Oxaprozin potassium reversibly and competitively inhibits cyclooxygenases (COX), thereby blocking the conversion of arachidonic acid to pro-inflammatory prostaglandins. This inhibits the formation of prostaglandins that are involved in pain, inflammation and fever.
A synthetic peptide vaccine based on the sequences of a translocation mutation of 2 transcriptional factor genes, PAX3 and FKHR. PAX3/FKHR fusion proteins are frequently found in patients with rhabdomyosarcomas. Vaccination with PAX3/FKHR peptide may stimulate the host immune response to elicit a cytotoxic T-cell response against tumor cells that express this PAX3/FKHR fusion protein.
A highly selective, small-molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase with potential antineoplastic activity. PF-00299804 specifically binds to and inhibits human EGFRs Her-1, Her-2, and Her-4, resulting in decreased tumor cell proliferation and survival of cells that overexpress these receptors. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=462567&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=462567&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C53398"" NCI Thesaurus)
An epoxomicin derivate with potential antineoplastic activity. PR-171 irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome, an enzyme responsible for degrading a large variety of cellular proteins. Inhibition of proteasome-mediated proteolysis results in an accumulation of polyubiquinated proteins, which may lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor growth. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=459751&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=459751&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C52196"" NCI Thesaurus)
An injectable ten percent solution of rose bengal disodium, an iodinated fluorescein derivative, with potential antineoplastic and radiosensitizing activities. When injected into tumor tissue, PV-10 specifically targets and concentrates in tumor cells, producing cytotoxic singlet oxygen when exposed to ionizing radiation. In addition, PV-10 may stimulate an anti-tumor immune response.
A biodegradable poly(ethylene glycol)-poly(D,L-lactide) copolymer micelle nanoparticle-entrapped formulation of paclitaxel with antineoplastic activity. Paclitaxel promotes microtubule assembly and prevents depolymerization, thus interfering with normal mitosis. The copolymer residue increases the water-solubility of paclitaxel and allows delivery of higher doses than those achievable with paclitaxel alone.
Paget disease involving the skin overlying the mammary gland, without accompanying invasive ductal or lobular breast carcinoma.
A well differentiated pancreatic neuroendocrine tumor which measures less than 0.5 cm in diameter and it is not associated with a hormonal syndrome.
Superficial vascularization of the cornea with infiltration of granulation tissue; an inflammatory exudate overlying the lining layer of synovial cells on the inside of a joint.
A papillary carcinoma of the thyroid gland measuring 10mm or less in diameter. The survival rates of patients with this type of carcinoma are the same with those of the normal population.
A parathyroid gland tumor that shares certain morphologic characteristics with parathyroid gland carcinomas (e.g. broad fibrous bands formation with or without hemosiderin deposition, presence of mitotic figures) but lacks unequivocal evidence of capsular or vascular invasion. It is considered a tumor of uncertain malignant potential (adapted from WHO, IARC Press, Lyon, 2004).
A parathyroid gland adenoma that contains mature adipocytes.
A pathologic finding about one or more characteristics of a specific cancer, following the rules of the TNM classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of a specific cancer, following the rules of the TNM classification system as they pertain to staging of regional lymph nodes.
TNM staging performed as part of pathologic specimen.
A rare benign or malignant germ cell tumor that arises from the pericardium. The reported cases have been teratomas and yolk sac tumors.
A localized or multifocal mesothelioma arising from the peritoneum. It predominantly occurs in women. It is characterized by the formation of papillae, covered by a single layer of blunt mesothelial cells. Mitotic figures are not present. There is no evidence of severe cytologic atypia. It has a relatively favorable clinical outcome, compared to diffuse malignant mesothelioma.
A condition resulted from the escape of blood around a heart valve, particularly around its leaflets.
An adverse event that extends continuously, without resolution between treatment cycles or courses.
Molecular variants of the desired biological product formed during manufacture and/or storage, which are active and have no deleterious effect on the safety and efficacy of the drug substance or drug product. These variants possess properties comparable to the desired product and are not considered impurities.
Processes that effect the level of a drug in the body.
The outcome that results from chemical interactions between a drug and another drug or food.
A B-cell acute leukemia characterized by the presence of lymphoblasts that carry a translocation between the BCR gene on chromosome 22 and the ABL1 gene on chromosome 9. It results in the production of the p190 kd or p210 kd fusion protein. It has an unfavorable clinical outcome.
An objective visual sensation that appears with the eyes closed and in the absence of visual light.
A mesenchymal neoplasm arising from the pilar sheath of the hair follicle.
A cutaneous leiomyoma arising from the arrector pili muscle.
A standardized extract containing the active alkaloid piperine, derived from the fruit of the plant Piper nigrum (black pepper) and/or the plant Piper longum L. (long pepper), with thermogenic properties. Co-ingestion of piperidine enhances the bioavailability of various nutrients, including beta-carotene, curcumin, selenium, pyridoxine and coenzyme Q10. In addition, this agent may exert anti-inflammatory and anti-tumor activities and may enhance the production of serotonin.
A tumor characterized by the presence of mature ganglion cells and neuronal differentiation, arising in the pituitary gland. It is often associated with the presence of pituitary gland adenomas. Symptoms include acromegaly and precocious puberty.
A pituitary gland adenoma with a diameter greater than 10 mm. Clinical manifestations include headache, visual field disturbances, pituitary insufficiency, and mild hyperprolactinemia.
A pituitary gland adenoma with a diameter equal or less than 10 mm.
A null cell pituitary gland adenoma, characterized by the presence of eosinophilic cells and mitochondrial abundance.
A morphologic variant of hepatocellular carcinoma, characterized by the presence of malignant cells which show marked variation in their size and shape. Bizarre mononuclear or multinucleated giant cells are often present.
A non-metastasizing soft tissue neoplasm characterized by the presence of a neoplastic stroma containing spindle cells, dilated thin-walled vessels lined by fibrin, and a chronic inflammatory infiltrate. The majority of cases develop in the subcutaneous tissues usually in the lower extremities and present as slow growing masses. Recurrences occur in approximately half of the cases.
Malignant mesothelioma that arises from the pleura. It is characterized by the presence of epithelioid and sarcomatoid components, with each component representing at least 10% of the tumor.
A biphasic synovial sarcoma arising in the pleural cavity.
Malignant mesothelioma that arises from the pleura and is characterized by the presence of dense collagenized stroma occupying at least 50% of the tumor. The malignant cells are arranged in a vague storiform pattern.
A low-grade malignant blood vessel neoplasm arising from the pleura. It is characterized by the presence of epithelioid endothelial cells. The neoplastic cells are arranged in cords and nests, which are embedded in a myxoid to hyalinized stroma.
Malignant mesothelioma that arises from the pleura and is characterized by the presence of cells with epithelioid morphology. The epithelioid cells usually have eosinophilic cytoplasm, bland nuclei, and form tubulopapillary, microglandular, or sheet-like patterns.
A rare extranodal lymphoma that arises from the pleura with no evidence of involvement of other sites at the time of diagnosis. This category includes primary effusion lymphoma and pyothorax-associated lymphoma.
A monophasic synovial sarcoma arising in the pleural cavity.
Malignant mesothelioma that arises from the pleura and is characterized by the presence of spindle-shaped cells forming fascicles, or that are distributed haphazardly resembling a sarcoma.
A synovial sarcoma arising in the pleural cavity.
A rare, non-invasive, localized or multifocal neoplasm that arises from the pleura. It is characterized by the presence of papillae with myxoid fibrovascular cores, lined by a single layer of mesothelial cells. The clinical course is usually indolent.
An infrequent chromophobic or slightly eosinophilic pituitary gland adenoma that shows immunoreactivity for more than one pituitary hormone, excluding the following two combinations: growth hormone/prolactin/TSH, and FSH/LH.
A compound that mimics the naturally occurring polyamines but is modified in such a way that its function differs from that of the natural polyamines and is usually biologically inactive. Polyamine analogues most likely exert their actions through their ability to displace the natural polyamines from their DNA binding sites. Since the natural polyamines are involved in numerous important cellular processes such as cell division, differentiation and membrane function, their displacement from the DNA binding site may lead to an inhibition of cell growth.
An intermediate, rarely metastasizing blood vessel neoplasm. It is characterized by the presence of a polymorphic cellular infiltrate.
Indicates the presence of tumor cells at the edge of a surgically excised specimen.
A high grade osteosarcoma arising in an irradiated bone.
The potassium salt form of aminosalicylic acid, an analog of aminobenzoic acid used to treat tuberculosis. Although the mechanism of action of potassium aminosalicylate remains to be elucidated, its effects on mycobacteria may be attributed to inhibition of folic acid or mycobactin (cell wall component) synthesis. This agent also inhibits the onset of drug resistance to streptomycin and isoniazid.
The state before the onset or development of clinical disease. Persons who have presymptomatic cancer already have developed the disease of cancer, which is in a pre-clinical state. 2005
An aggressive primary cutaneous B-cell lymphoma, usually involving the lower leg. It is composed of a generally monotonous proliferation of immunoblasts, or less frequently centroblasts, with few admixed reactive cells. This type of lymphoma occurs most often in elderly women who present with rapidly growing tumors, usually on one or both legs. Dissemination to extracutaneous sites is frequent. Treatment with combination chemotherapy is usually required.
A rare type of primary cutaneous diffuse large B-cell lymphoma that does not belong in the group of primary cutaneous diffuse large B-cell lymphomas, leg type, or the group of primary cutaneous follicle center lymphomas. It includes subtypes/entities of diffuse large B-cell lymphoma (e.g. intravascular large B-cell lymphoma, plasmablastic lymphoma, T-cell/histiocyte rich lymphoma) that can involve the skin as the primary anatomic site. Such cases, unlike their nodal counterparts, usually have an excellent prognosis.
Focal scarring of the glomerulus, which may result in isolated proteinuria or nephrotic syndrome, which affects only part of the glomerulus and only some of the glomeruli. The condition is considered primary in cases for which no underlying cause has been identified.
A squamous cell carcinoma that arises centrally from the jaw. It derives from odontogenic epithelial remnants. It includes solid type squamous cell carcinoma, squamous cell carcinoma that arises from an odontogenic cyst, and squamous cell carcinoma that derives from a keratocystic odontogenic tumor.
A rare, well-differentiated, keratinizing squamous cell carcinoma that arises centrally from the jaw and is associated with the presence of a keratocystic odontogenic tumor.
A diffuse large B-cell lymphoma that is localized to the lungs at the time of presentation. Signs and symptoms include cough, dyspnea, and hemoptysis.
Referring to the fact that the original site of growth of a metastatic cancer is unknown or uncertain.
A clinical finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v6 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, endoscopy, biopsy or laboratory testing.
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v6 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
Prostate cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Prostate cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Prostate cancer with metastasis to non-regional lymph node(s). (from AJCC 6th and 7th Eds.)
Prostate cancer with metastasis to bone(s). (from AJCC 6th and 7th Eds.)
Prostate cancer with metastasis to other site(s) with or without bone disease. (from AJCC 6th and 7th Eds.)
Prostate cancer with no positive regional nodes. (from AJCC 6th and 7th Eds.)
Prostate cancer with metastases in regional node(s). (from AJCC 6th and 7th Eds.)
Prostate cancer in which the regional lymph nodes were not sampled. (from AJCC 6th and 7th Eds.)
Prostate cancer confined to the prostate gland. (from AJCC 6th and 7th Eds.)
Prostate cancer limited to one-half or less of one lobe of the prostate gland. (from AJCC 6th and 7th Eds.)
Prostate cancer involving more than one-half of one lobe, but not both lobes of the prostate gland. (from AJCC 6th and 7th Eds.)
Prostate cancer involving both lobes of the prostate gland. (from AJCC 6th and 7th Eds.)
Prostate cancer with extraprostatic extension. (from AJCC 6th and 7th Eds.)
Prostate cancer with seminal vesicle invasion. (from AJCC 6th and 7th Eds.)
The formation of a blood clot that is attached to or near an artificial heart valve; this can cause dysfunction of the valve, and possibly lead to an embolic event should the thrombus become dislodged.
A change in the amino acid sequence of a wild-type protein, resulting from aberrant excision of in-frame protein sequences (inteins) from a precursor protein followed by ligation of the flanking sequences (exteins).
A rare neoplastic polyp that arises from the stomach. It is characterized by the presence of gastric epithelial differentiation and pyloric gland-type tubular structures, which are closely packed.
An aggressive diffuse large B-cell lymphoma arising in the pleural cavity of patients with a history of long standing pyothorax. Patients present with chest and back pain, fever, productive cough, dyspnea, and hemoptysis.
An infection caused by pus-producing organisms.
Fever reaction due to the presence of bacterial endotoxins.
An electrocardiographic finding of a QS wave, which is atypical.
An outcome or conclusion that can be arrived at by measurement.
A synthetic vaccine used for cancer immunotherapy also known as Ras(cis 12)-Vaccinia Vaccine, RASVAC-C is based on a mutant peptide epitope of the Ras oncoprotein at codon 12 that induces recognition and induction of tumor-specific, cell-mediated immune responses. Ras is an intracellular GTP-binding protein involved in signal transduction and regulation of proliferation and differentiation. (NCI04)
A synthetic vaccine used for cancer immunotherapy also known as Ras(val 12)-Vaccinia Vaccine, RASVAC-C is based on a mutant peptide epitope of the Ras oncoprotein at codon 12 (valine instead of glycine) that induces recognition and induction of tumor-specific, cell-mediated immune responses. Ras is an intracellular GTP-binding protein involved in signal transduction and regulation of proliferation and differentiation. (NCI04)
A gene rearrangement involving the RET proto-oncogene. RET gene rearrangements are associated with several different neoplastic conditions.
A higher than intended cumulative dose of radiation to a single field.
The complex of symptoms characterizing the disease known as radiation injury, resulting from excessive exposure (greater than 200 rads or 2 gray) of the whole body (or large part) to ionizing radiation. The earliest of these symptoms are nausea, fatigue, vomiting, and diarrhea, which may be followed by epilation, hemorrhage, inflammation of the mouth and throat, and general loss of energy. In severe cases, where the radiation exposure has been approximately 1000 Rad (10 gray) or more, death may occur within two to four weeks. Those who survive six weeks after the receipt of a single large dose of radiation to the whole body may generally be expected to recover. (U.S. Nuclear Regulatory Commission).
The use of compounds targeting anatomic structures to enhance radiation cytotoxicity.
A non-neoplastic proliferation of C-cells in the thyroid gland caused by external stimuli such as hypercalcemia and chronic lymphocytic thyroiditis.
A multicellular process that regulates the extent of response to a stimulus either by modulation of active receptors or inhibition of intracellular catalytic activities that are initiated by receptor activation.
A multicellular process that regulates the number of tyrosine kinase-associated transmembrane receptors, by means of increased internalization or decreased expression of the transmembrane receptor. This process is involved in dampening the response to extracellular signals.
A plasmid DNA encoding human L523S, an RNA-binding protein that belongs to the KOC (K homology domain containing protein overexpressed in cancer) family, with potential antineoplastic activity. Vaccination with L523S DNA may stimulate a cytotoxic T lymphocytes (CTL) response against tumor cells that express the L523S protein. As an oncofetal protein, L523S is normally expressed in early embryonic tissue, but is overexpressed in certain cancer cell types.
An immunoconjugate of recombinant CD4 antigen (rCD4) covalently linked to an immunoglobulin G heavy chain with activity against human immunodeficiency virus (HIV). Recombinant CD4 antigen competitively binds to the envelope glycoprotein gp120 of HIV, prevents the attachment of gp120 to CD4 on T lymphocytes, and acts as an HIV fusion inhibitor; the immunoglobulin G portion extends the length of time that rCD4 stays in the body.
A cancer vaccine comprised of a recombinant modified vaccinia Ankara (MVA) viral vector encoding the 5T4 fetal oncoprotein (MVA-h5T4). Vaccination with recombinant modified vaccinia Ankara-5T4 vaccine may stimulate the host immune system to mount a humoral and cytotoxic T lymphocyte (CTL) response against tumor cells expressing 5T4 fetal oncoprotein antigen, resulting in tumor cell lysis. The MVA viral vector, derived from the replication-competent strain Ankara, is a highly attenuated, replication-defective vaccinia strain incapable of virion assembly.
A recombinant vaccinia virus encoding a modified peptide of the gp100 melanoma-melanocyte antigen with potential use in cancer immunotherapy. gp100 human antigen is a wild type self-antigen expressed by melanocytes, pigmented retinal cells and most melanomas. This recombinant vaccinia Mgp100 encodes a fragment epitope of gp100 bearing 2 amino acids substitution; T->M at position 210 and 288 A ->V at position 210. This modification may stimulate tumor infiltrating lymphocytes (TIL) more efficiently.
A cancer vaccine consisting of an inactivated recombinant vaccinia virus encoding epitope peptides derived from melanoma-related HLA-A2-restricted tumor-associated antigens (TAAs), including Melan-A(27-35), gp100(280-288) and tyrosinase(1-9), and two co-stimulatory B7 proteins, B7.1 (CD80) and B7.2 (CD86). Upon administration, recombinant vaccinia-multiepitope melanoma peptides-B7.1-B7.2 vaccine may stimulate a cytotoxic T-lymphocyte response against melanoma cells that express TAAs which share epitopes with the epitope peptides expressed by the vaccine viral vector, resulting in tumor cell lysis; vaccine viral vector-expressed co-stimulatory proteins B7.1 and B7.2 may enhance the cytotoxic T-lymphocyte immune response to the TAAs.
A cancer vaccine consisting of a truncated recombinant HER2 peptide (dHER2) with potential antineoplastic activity. Upon administration, recombinant dHER2 vaccine may stimulate the host immune response to mount a cytotoxic T-lymphocyte response against tumor cells that overexpress the HER2 protein, resulting in tumor cell lysis. The HER2 protein is a tumor-associated antigen (TAA) that is overexpressed in a variety of cancers. dHER2 includes the extracellular domain (ECD) and a part of the intracellular domain (ICD) of the HER2 protein.
One of the possible results of an adverse event outcome where the subject recuperated but retained pathological conditions resulting from the prior disease or injury.
One of the possible results of an adverse event outcome that indicates that the event has improved or recuperated.
An unusual rectal carcinoma characterized by the presence of glandular and squamous carcinomatous components. The two carcinomatous components may be admixed within the tumor, or the two may appear separately in different areas.
An invasive adenocarcinoma of the rectosigmoid area characterized by the presence of pools of extracellular mucin. Malignant glandular epithelial cells are present in the mucin collections. Mucin constitutes more than 50% of the lesion.
An infiltrating adenocarcinoma arising from the rectosigmoid area. It is characterized by the presence of malignant glandular cells with prominent intracytoplasmic mucin. These cells constitute more than 50% of the malignant cellular population.
TNM staging performed for recurrent cancer.
Reemergence of extraskeletal myxoid chondrosarcoma after a period of remission
The reemergence of a pheochromocytoma following surgical removal.
The re-emergence of a pituitary gland neoplasm after a period of remission.
An adverse event that occurs and resolves during a cycle or course of medical intervention and then reoccurs in a later cycle or course.
A tumor deposit found in a resected specimen in the fatty adjacent tissue and not contained within lymphoid tissue.
A pheochromocytoma that invades surrounding tissues adjacent to the adrenal glands.
Peripheral blood lymphocytes (PBL) harvested from the blood of a renal cancer patient and exposed in vitro to renal tumor-associated antigens (TAA). Introducing these renal tumor-reactive autologous peripheral blood lymphocytes back to the same patient target tumor cells expressing these TAAs and could induce a cytotoxic T-cell-mediated immune response against renal cell cancer.
Tumor infiltrating lymphocytes (TIL) harvested directly from infiltrate of a patient's renal tumor and cultured with interleukin-2 to expand the TIL cell population. Tumor infiltrating lymphocytes have specific activity against the tumor from which they are derived. Introducing these renal tumor-reactive autologous tumor infiltrating lymphocytes back into the same patient may enhance a cytotoxic T-cell-mediated immune response against the renal cancer cells.
An inherited change of a single base in a DNA sequence from an organism that changes the specific pattern of bases recognized and hydrolyzed by a restriction endonuclease enzyme. Restriction site polymorphisms can either create or abolish recognition sites for restriction enzymes.
Any environment-to-cell communication in which the ligand retinoic acid binds to intracellular retinoic acid receptors. This process is involved in embryonic developmental patterning.
A process that involves the binding of a retinoid to an intracellular retinoid receptor. These interactions have diverse functions throughout the body, including roles in vision, activation of tumor suppressor genes, and regulation of cell proliferation, differentiation and immune function.
A replication-incompetent, pathotropic, tumor matrix (collagen)-targeted, retroviral vector encoding an N-terminal deletion mutant form of the cyclin G1 gene with potential antineoplastic activity. Under the control of a hybrid long-terminal repeat/cytomegalovirus (CMV) promoter, retrovector encoding mutant anti-cyclin G expresses the mutant cyclin G1 construct, resulting in disruption of tumor cell cyclin G1 activity and decreased cellular proliferation and angiogenesis. This agent preferentially targets collagen of the tumor matrix because of the incorporation of the collagen-binding domain of von Willebrand factor (vWF) on the retrovector surface. Exploiting the collagen-targeting mechanism of vWF permits delivery of the retrovector to tumor sites where angiogenesis and collagen matrix exposure occur.
Ribosomal Function Inhibition is a process that prevents normal translation, typically by interfering with ribosomal protein subunits or RNA components.
A synthetic small molecule with potential antineoplastic properties. SB-743921 selectively inhibits kinesin spindle protein (KSP), an important protein involved in the early stages of mitosis that is expressed in proliferating cells. Inhibition of KSP results in inhibition of mitotic spindle assembly and interrupts cell division, thereby causing cell cycle arrest and induction of apoptosis.
A change in the nucleotide sequence of the SDHB gene.
A change in the nucleotide sequence of the SDHC gene.
A change in the nucleotide sequence of the SDHD gene.
The expression of fusion proteins that result from a chromosomal aberration, t(X;18)(p11.2;q11.2), which fuses the first 10 exons of the SS18 gene with exon six of one of three SSX genes (SSX1, SSX2 or SSX4) and is associated with synovial sarcoma.
An adjuvant comprised of saponin, derived from the bark of Quillaia saponaria Molina, cholesterol and phospholipid with antigen-delivery and immunostimulatory activities. This saponin-based adjuvant in combination with various antigens, including those for human papilloma virus (HPV), hepatitis C virus (HCV), and the human cancer antigen NY-ESO-1, may result in potent antibody, CD4+ T-helper-cell, and CD8+ cytotoxic T-cell responses against the targeted antigen. In addition, this agent may reduce the amount of antigen necessary to induce an efficient immune response in the host.
A morphologic variant of hepatocellular carcinoma characterized by the presence of malignant spindle cells or atypical giant cells.
Additional, separate neoplastic nodules surrounding a central neoplastic lesion.
A well-circumscribed rare morphologic variant of fibrosarcoma, that arises from the soft tissue. It is characterized by the presence of nests of malignant epithelioid fibroblasts and sclerotic collagen stroma formation.
A rare type of thymoma, characterized by an exuberant amount of collagen-rich stroma.
Focal segmental glomerulosclerosis due to another medical condition.
An osteosarcoma arising from a pre-existing lesion of the bone, usually Paget disease, or due to radiation therapy.
The common saw-tooth architectural pattern observed within hyperplastic polyps.
A rare adenoma of the adrenal cortex that produces androgens or estrogens.
A carcinoma arising from the nasal cavity or paranasal sinuses.
A rare, highly aggressive carcinoma that arises from the sinonasal tract. It is characterized by the presence of small to medium size malignant cells. The prognosis is poor.
An uncommon carcinoma that arises from the skin. It is characterized by the presence of malignant glandular and malignant squamous cellular components.
A cavernous hemangioma arising from the skin.
An invasive adenocarcinoma that arises from the small intestine. It is composed of malignant glandular cells which contain intracytoplasmic mucin. Often, the infiltrating glandular structures are associated with mucoid stromal formation.
An invasive adenocarcinoma that arises from the small intestine. It is characterized by the presence of malignant glandular cells in which the nucleus is pressed to one side by the presence of intracytoplasmic mucus.
A carcinoma that arises from the small intestine. It is composed of malignant squamous cells.
A usually polypoid neoplasm that arises from the glandular epithelium of the small intestine. It is characterized by a tubular architectural pattern. The neoplastic glandular cells have dysplastic features.
A neoplasm that arises from the glandular epithelium of the small intestine. It is characterized by tubular and villous architectural patterns. The neoplastic glandular cells have dysplastic features.
A carcinoma that arises from the small intestine. It is composed of malignant epithelial cells which do not display evidence of glandular, squamous, or transitional cell differentiation.
A neoplasm that arises from the glandular epithelium of the small intestine. It is characterized by a villous architectural pattern. The neoplastic glandular cells have dysplastic features.
A morphologic variant of angioleiomyoma characterized by the presence of numerous small, slit-like vascular channels.
The most common morphologic variant of glomus tumor. It is characterized by the presence of a nest of glomus cells surrounding capillary sized vessels.
An osteochondroma affecting a single anatomical site.
A prolactin producing pituitary gland adenoma composed of relatively large, chromophobic or slightly acidophilic cells with well developed, abundant endoplasmic reticulum, and many immature secretory granules. Mature secretory granules are sparse.
A growth hormone producing pituitary gland adenoma composed of small, round cells containing fibrous bodies and scarce, small secretory granules.
A chronic adhesive arachnoiditis in the spinal arachnoid, with root and spinal cord symptoms similar to those caused by pressure from a tumor.
A sporadic adenocarcinoma that arises from the gastric mucosa and is characterized by the presence of poorly cohesive malignant cells and absence of glandular formations.
A non-hereditary medullary carcinoma of the thyroid gland not associated with multiple endocrine neoplasia. The majority of thyroid gland medullary carcinomas are sporadic.
A sporadic thyroid gland medullary carcinoma measuring less than 10mm in diameter.
A morphologic variant of squamous cell lung carcinoma characterized by nuclear palisading.
A morphologic variant of squamous cell lung carcinoma characterized by the presence of clear cells.
A morphologic variant of squamous cell lung carcinoma characterized by the presence of papillary structures.
A poorly differentiated morphologic variant of squamous cell lung carcinoma characterized by the presence of small tumor cells with focal squamous differentiation.
A rapidly growing primary carcinoma of the thyroid gland composed of malignant squamous cells. The clinical course is usually aggressive.
Condition where there are a greater number of inhalations relative to the number of exhalations.
A self-limiting, rapidly growing, non-encapsulated benign neoplasm arising from the subcutaneous tissues. It is characterized by the growth of plump spindle-shaped fibroblasts in a storiform pattern, multinucleated osteoclast-like giant cells, red blood cell extravasation, chronic inflammatory cells, and high mitotic activity.
Decentration, or malposition of intraocular lens; zonular dehiscence or lens malposition caused by zonular or parsplana fixation.
A benign or malignant extra-adrenal sympathetic paraganglioma arising from paraganglia located along the aorta, including suprarenal, infrarenal, and renal hilar sites. In functional tumors, the hypersecretion of catecholamines results in hypertension.
Wearing away of the surface of a suture as a result of bending and frictional forces.
A cancer vaccine containing synthetic epitope peptides derived from melanoma tumor-associated antigens (TAAs), including melanoma-melanocyte antigen gp100(280-288), melanoma-associated antigen tyrosinase(1-9), and melanoma-associated antigen melan-A(27-35). Upon administration, synthetic melanoma-associated antigens vaccine may stimulate a cytotoxic T-lymphocyte immune response against melanoma cells that express TAAs which share epitopes with the vaccine epitope peptides, resulting in tumor cell lysis.
A synthetic, third generation taxane with potential antineoplastic activity. TPI 287 binds to tubulin and stabilizes microtubules, resulting in inhibition of microtubule assembly/disassembly dynamics, cell cycle arrest at the G2/M phase, and apoptosis.
A molecular abnormality indicating rearrangement of the NTRK1 gene.
An inherited polymorphism in eukaryotic DNA that results from variations in the number of tandem repeat nucleotide sequences, which are end-to-end adjacent copies of a short (2 to 60 nucleotides) DNA sequence located between two restriction endonuclease recognition sites. These are referred to as variable number of tandem repeats (VNTR), and the number of alleles at these loci can vary from 2 to more than 20. VNTRs provide important genetic information that is used to identify an individual via the DNA fingerprinting technique.
The finding of bodily harm due to the poisonous effects associated with the action or administration of therapeutic agents.
A primary thymic carcinoid tumor, characterized by a high mitotic rate often associated with the presence of necrosis and nuclear pleomorphism. This type of thymic carcinoid tumor has a more aggressive clinical course, compared to typical thymic carcinoid tumors.
A benign thymic tumor morphologically resembling fibroadenoma of the breast.
A low-grade extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue that affects the thymus. It is characterized by the presence of centrocyte-like or monocytoid lymphocytes that surround reactive lymphoid follicles. There is infiltration of the thymic epithelium by lymphocytes and formation of lymphoepithelial lesions. It is associated with the presence of autoimmune disease, most frequently Sjogren syndrome. Patients are usually asymptomatic and the tumor is detected incidentally as a mediastinal mass on chest x-ray. A minority of patients present with dyspnea, hemoptysis, and chest pain. The prognosis is excellent.
A primary thymic carcinoid tumor, characterized by the presence of uniform, polygonal neoplastic cells, a low mitotic rate, and absence of necrosis.
A point mutation involving the substitution of Adenosine (a purine base) for Thymidine (a pyrimidine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A point mutation involving the substitution of Cytosine (a pyrimidine base) for Thymidine (a pyrimidine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A point mutation involving the substitution of Guanosine (a purine base) for Thymidine (a pyrimidine base) in a DNA sequence from eukaryotic or prokaryotic organisms. This abnormality can be either heritable or occur somatically.
A thyroid gland adenoma composed of follicular cells with cytoplasmic clearing.
A thyroid gland adenoma containing follicular cells with large hyperchromatic nuclei. The clinical course is benign.
A thyroid gland adenoma affecting predominantly children and adolescents. It is composed of branching papillary structures and follicles.
A thyroid gland adenoma composed of follicles and mature adipocytes.
A primary carcinoma of the thyroid gland containing a medullary carcinoma component that is immunohistochemically positive for calcitonin, and follicular cell carcinoma structures that are immunohistochemically positive for thyroglobulin.
A thyroid gland adenoma composed of follicles and characterized by the presence of abundant extracellular mucin.
A rare, circumscribed or encapsulated neuroendocrine tumor arising from the thyroid gland. Microscopically, it is characterized by the presence of tumor cells arranged in a nesting (Zellballen) growth pattern. The reported cases have followed a benign clinical course.
A thyroid gland adenoma characterized by the presence of signet ring cells that stain positive for thyroglobulin.
A mature or immature multicystic germ cell tumor involving or being in direct continuity with the thyroid gland. Microscopically, many tissue types and growth patterns may be seen. According to the presence of mature or immature tissue elements, these lesions are graded from I to IV. The prognosis depends on the age of the patient, the tumor size at presentation, and the histologic grade.
A thyroid gland adenoma producing thyroxin. It is associated with hyperthyroidism. Radioactive iodine scan reveals a hot nodule.
An abnormality that results from a functional change in the mRNA sequence at the translation initiation codon. In eukaryotic organisms, the initiation codon is always AUG. A mutation in either DNA or corresponding mRNA that alters this initiation sequence causes termination of mRNA translation. No functional protein product is synthesized when a translation initiation abnormality exists.
A biologic subset of diffuse large B-cell lymphomas (DLBCL) that do not overexpress the genes whose overexpression characterizes the germinal center B-cell-like and activated B-cell-like DLBCL. Morphologically, these lymphomas are either immunoblastic or centroblastic. Patients with this type of diffuse large B-cell lymphoma are reported to have a less favorable outcome, similar to those with an activated B-cell-like gene expression profile.
A pleuropulmonary blastoma characterized by a solid pattern and sarcomatous features. It usually follows an aggressive clinical course.
A pleuropulmonary blastoma composed of malignant small cells and characterized by the presence of a sarcomatous component. It usually follows an aggressive clinical course.
A pleuropulmonary blastoma composed of malignant small cells. Sarcomatous features are absent.
A synthetic peptide consisting of amino acid residues 146 through 156 of the enzyme tyrosinase, a protein frequently expressed by melanoma cells, with antitumor activity. Vaccination with tyrosinase:146-156 peptide may stimulate cytotoxic T lymphocyte response against tyrosinase-expressing tumor cells, resulting in decreased tumor growth and cell lysis.
A UV Mutation Abnormality is an altered heritable state of the genetic DNA nucleotide sequence caused by exposure to ultraviolet light (UV) that results mostly in the formation of cyclobutane pyrimidine dimers and (6-4) photoproducts. UV-damaged DNA interferes with DNA replication and transcription, and can lead to cell killing or mutagenesis if the damage is not properly repaired.
Changes in the fluid pressure inside the eye.
An infiltrating high grade mesenchymal tumor arising from the uterine corpus, cervix, vagina, and the ovary.
A lesion arising from or having a single location.
Breast carcinoma of one breast, or one side of the breast.
Expression of a fusion protein that results from the translocation mutation t(V;11)(v;q23), which involves the human MLL gene and various fusion gene partners. The fusion transcript is the result of the translocation of genetic material from any one of several chromosomes to the 11q23 region. This fusion protein is associated with acute myelomonocytic leukemia.
An angiomyofibroblastoma arising from the vagina.
An antisense oligonucleotide with potential antiangiogenesis activity. Vascular endothelial growth factor (VEGF) antisense oligonucleotide binds directly to binds VEGF A/C/D mRNA, leading to mRNA degradation and the inhibition of VEGF A-mediated angiogenesis and VEGF C/D-mediated lymphangiogenesis.
Sudden drop of the blood pressure, bradycardia, and peripheral vasodilation that may lead to loss of consciousness. It results from an increase in the activity of the vagus nerve. It may be triggered by emotions of fear or pain or gastrointestinal upset and may be relieved by lying down while keeping the legs elevated.
A recombinant human fibroblast growth factor-20 (rhFGF-20) protein with pro-proliferative activity. Velafermin stimulates DNA synthesis and cell proliferation, specifically promoting epithelial and mesenchymal cell proliferation, and may prevent radiation or chemotherapy-induced oral mucositis.
A morphologic variant of angioleiomyoma characterized by the presence of thick-walled veins.
A term referring to the presence of tumor emboli or tumor masses within veins.
A cardiac myxoma arising from the ventricle.
An angiomyofibroblastoma arising from the vulva.
An intermediate grade well differentiated tumor with neuroendocrine differentiation that arises from the pancreas. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3-20%.
A thymoma that spreads by direct extension into adjacent tissues (lung, pericardium, or large vessels). This type of thymoma usually appears invasive at the time of excision.
An orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. XL184 strongly binds to and inhibits several tyrosine receptor kinases. Specifically, XL184 appears to have a strong affinity for the hepatocyte growth factor receptor (Met) and vascular endothelial growth factor receptor 2 (VEGFR2), which may result in inhibition of tumor growth and angiogenesis, and tumor regression. This agent has also been shown to inhibit mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (Flt3) and tyrosine-protein kinase receptor (Tie-2). Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=461103&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=461103&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C52200"" NCI Thesaurus)
An orally bioavailable, small molecule receptor tyrosine kinase inhibitor with potential antineoplastic activity. XL820 binds to and inhibits the receptor tyrosine kinases for vascular endothelial growth factor (VEGF), c-kit, and platelet-derived growth factor (PDGF). In tumor models of breast carcinomas, gliomas, and leukemia, this agent exhibits dose-dependent growth inhibition and has been shown to cause tumor regression.
A radioimmunoconjugate comprised of the chimeric monoclonal antibody cG250 conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and labeled with the beta-emitting radioisotope yttrium 90. The antibody moiety of yttrium 90 DOTA chimeric monoclonal antibody cG250 binds to renal cell carcinoma cells expressing the G250 antigen, thereby selectively delivering a cytotoxic dose of beta radiation.
A radiofluorinated 2-nitroimidazole derivate with hypoxia-specific tracer activity. Misonidazole is reduced under hypoxic conditions and in reduced form covalently binds to macromolecules in hypoxic cells. 18F (fluorine-18) radiofluorination of misonidazole to form 18F-fluoromisonidazole allows radioisotopic imaging of reduced misonidazole bound to macromolecules in hypoxic cells.
A synthetic peptide consisting of amino acids 27 through 35 of the melanoma differentiation antigen MART-1. 27-35(27L) MART-1 has a leucine substitution at amino acid position 27 to improve binding to HLA-A*0201. Vaccination with this agent may stimulate the host immune response to mount a cytotoxic T-lymphocyte response against melanoma cells expressing MART-1.
A topical gel containing a peptide derived from the human papillomavirus (HPV). Application of 851B gel may stimulate the host immune system to trigger a cytotoxic T-lymphocyte response to cells that express HPV.
A molecular genetic abnormality indicating the presence of multiple copies of the MET gene.
A change in the nucleotide sequence of the MYC gene.
A synthetic peptide cancer vaccine consisting of amino acid residues 209 through 217 of the glycoprotein 100 (gp100) melanoma antigen, with a methionine substitution at position 210 designed to improve immunogenicity. Vaccination with gp100:209-217(210M) peptide may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing gp100.
A synthetic peptide vaccine consisting of amino acids 209 through 217 of the glycoprotein 100 (gp100) melanoma antigen with an endoplasmic reticulum signal sequence (ES) to increase binding activity. Vaccination with gp100:ES209-217(210M) may stimulate the host immune system to mount a cytotoxic T lymphocyte response against tumor cells positive for gp100, resulting in decreased tumor growth. (NCI04)
A clinical and/or pathologic regional lymph nodes TNM finding usually indicating the presence of metastasis in one to three regional lymph nodes.
An antigen-specific DNA cancer vaccine consisting of the coding sequences of a signal peptide (pNGVL4a-Sig), a detox form of the human papillomavirus type 16 (HPV-16) antigen E7, and the heat shock protein 70 (HSP70). Upon administration, this vaccine may generate potent cytotoxic CD8(+) T-cell responses against E7-expressing tumor cells, resulting in tumor cell death.
A pathologic primary tumor TNM stage finding. The definition of pT1a stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pT1a stage finding is defined as follows: cancer with tumor size more than 0.1 cm, but not more than 0.5 cm in greatest dimension; for lung cancer, pT1a stage finding is defined as follows: cancer with a tumor size of 2 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT1b stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pT1b stage finding is defined as follows: cancer with tumor size more than 0.5 cm, but not more than 1.0 cm in greatest dimension; for lung cancer, pT1b stage finding is defined as follows: cancer with a tumor size more than 2 cm but 3 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT1c stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pT1c stage finding is defined as follows: cancer with tumor size more than 1.0 cm, but not more than 2.0 cm in greatest dimension; for fallopian tube cancer, pT1c stage finding is defined as follows: cancer with tumor limited to one or both tubes with extension onto or through the tubal serosa, or with malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT2a stage finding depends on the particular type of cancer that it refers to; for example, for prostate cancer, pT2a stage finding is defined as follows: cancer limited to one-half or less of one lobe of the prostate gland; for lung cancer, pT2a stage finding is defined as follows: cancer with a tumor size more than 3 cm but 5 cm or less in greatest dimension. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT2b stage finding depends on the particular type of cancer that it refers to; for example, for prostate cancer, pT2b stage finding is defined as follows: cancer involving more than one-half of one lobe, but not both lobes of the prostate gland; for lung cancer, pT2b stage finding is defined as follows: cancer with a tumor size more than 5 cm but 7 cm or less in greatest dimension. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT2c stage finding depends on the particular type of cancer that it refers to; for example, for prostate cancer, pT2c stage finding is defined as follows: cancer involving both lobes of the prostate gland; for fallopian tube cancer, pT2c stage finding is defined as follows: cancer with pelvic extension and malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT3a stage finding depends on the particular type of cancer that it refers to; for example, for cervical cancer, pT3a stage finding is defined as follows: cancer involves lower third of vagina, without extension to pelvic wall; for kidney cancer, pT3a stage finding is defined as follows: cancer with tumor grossly extending into the renal vein or its segmental (muscle containing) branches or tumor invading perirenal and/or renal sinus fat but not beyond Gerota's fascia. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT3b stage finding depends on the particular type of cancer that it refers to; for example, for cervical cancer, pT3b stage finding is defined as follows:cancer extends to pelvic wall and/or causes hydronephrosis or nonfunctioning kidney; for kidney cancer, pT3b stage finding is defined as follows: cancer with tumor grossly extending into the vena cava below the diaphragm. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT3c stage finding depends on the particular type of cancer that it refers to; for example, for kidney cancer, pT3c stage finding is defined as follows: cancer with tumor grossly extending into the vena cava above the diaphragm, or invading the wall of the vena cava; for fallopian tube cancer, pT3c stage finding is defined as follows: cancer with peritoneal metastasis outside the pelvis and more than 2 cm in diameter. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT4a stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pT4a stage finding is defined as follows: cancer with extension to the chest wall, not including the pectoralis muscle; for thyroid cancer, pT4a stage finding is defined as follows: cancer with moderately advanced local disease. Tumor of any size extending beyond the thyroid gland capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve. (from AJCC 7th Ed.)
A pathologic primary tumor TNM stage finding. The definition of pT4b stage finding depends on the particular type of cancer that it refers to; for example, for breast cancer, pT4b stage finding is defined as follows: cancer with ulceration and/or ipsilateral satellite nodules and/or edema (including peau d'orange) of the skin, which do not meet the criteria for inflammatory carcinoma; for gastric cancer, pT4b stage finding is defined as follows: cancer with tumor invading adjacent structures. (from AJCC 7th Ed.)
An immunotoxin consisting of the monoclonal antibody anti-Tac directed against the interleukin 2 receptor (also known as IL-2R or CD25) conjugated to a derivative of the pseudomonas exotoxin. M A Tac conjugated pseudomonas exo is cytotoxic against T lymphocytes that express IL-2R. (NCI04)
A precursor T-cell lymphoblastic leukemia that involves the mediastinum. It usually affects adolescent and young adult males. It is treated with aggressive chemotherapy and radiation.
An adenoma that arises from the appendix. It is characterized by prominent serration of the glands and the presence of generalized low-grade dysplasia.
A cardiac rhabdomyoma characterized by the presence of neoplastic large striated muscle cells with clear cytoplasm and spider cells.
A vaccine consisting of a plasmid DNA encoding the human prostate-specific membrane antigen (PSMA). Upon administration, expressed PSMA may stimulate a cytotoxic T cell response against tumor cells that express this antigen, resulting in tumor cell lysis. (NCI05)
A carcinoma that arises from the small intestine. It is composed of malignant glandular cells and malignant squamous cells.
A primary adenocarcinoma of the stomach in a patient with no family history of gastric cancer or inherited high risk mutations.
A cancer finding in the TNM system that is not specifically identified as a clinical, pathologic, recurrent (retreatment), or autopsy classification using an accepted prefix in accordance with TNM classification guidelines. Though the 6th Edition of the AJCC Cancer Staging Manual indicates that unspecified TNM staging descriptors may be considered synonymous with the corresponding fully specified clinical category, such omission may lead to ambiguity in meaning, and in practice unqualified descriptors are frequently used with other intended meanings. The generic TNM concepts in the NCI Thesaurus are intended to explicitly reflect this lack of specification.
A microscopic finding indicating the presence of cells with glandular differentiation in a tumor sample.
A melanoma of the skin arising from a congenital melanocytic nevus.
A rare lymphoproliferative disorder that affects the lungs. It is characterized by the presence of an angiocentric and angiodestructive polymorphic cellular infiltrate composed of EBV-positive neoplastic B-lymphocytes and reactive T-lymphocytes. The majority of patients present with bilateral nodular lesions in the lungs. The prognosis depends on the histologic grade of the lesions. One third of patients with grade 1 lesions and two thirds of patients with grade 2 lesions progress to non-Hodgkin lymphoma. Grade 3 lesions, by definition, are classified as non-Hodgkin lymphomas.
An aggressive variant of squamous cell carcinoma that arises from the nasopharynx. It is characterized by the presence of small malignant cells with hyperchromatic nuclei and scant amount of cytoplasm forming lobules with peripheral palisading. Comedonecrosis may be present.
A dietary supplement to support joint health. Ingredients include ascorbic acid, chicken collagen II, methylsulfonylmethane, cetyl myristoleate 5%, lipase, bromelain, and turmeric extract.
A cell-based vaccine composed of autologous lymphoblastoid B cells activated against Epstein-Barr virus (EBV) in vitro with potential immunoprotective activity. Upon prophylactic administration, this vaccine may stimulate specific cytotoxic T-lymphocyte (CTL) and antibody responses against EBV-transformed B cells, thereby preventing an EBV-induced post-transplantation lymphoproliferative disorder.
A cancer vaccine containing of a synthetic form of the renal cell carcinoma (RCC)-associated antigen G250 with potential antineoplastic activity. Vaccination with G250 peptide vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the G250 antigen, resulting in decreased tumor growth. Found in the majority of renal cell carcinomas, G250 is a cell surface tumor-associated antigen (TAA) that contains an HLA-A2.1-restricted epitope that is recognized by CTLs.
A capillary hemangioma arising from the heart.
A benign or malignant extra-adrenal paraganglioma arising from the cerebellum.
A morphologic variant of lung sarcomatoid carcinoma composed of a mixture of non-small cell lung carcinoma and a sarcomatous component.
A rare, low-grade exophytic adenocarcinoma with papillary growth that arises from the epithelium of the nasopharynx. If it is completely removed, the prognosis is excellent.
A cancer vaccine comprised of a synthetic peptide derived from the mucin 1 (MUC1) antigen with potential antineoplastic activity. Upon administration, MUC1 peptide vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the MUC1 antigen, resulting in decreased tumor growth. Overexpressed on many tumor cells, MUC1 antigen, a mammary-type apomucin, is a high-molecular-weight transmembrane glycoprotein.
An invasive breast carcinoma showing differentiation towards bone structures.
A clinical stage I or II non-Hodgkin lymphoma without any of the following risk factors: large mediastinal mass, extranodal spread, elevated erythrocyte sedimentation rate, involvement of at least three lymph node areas, and B symptoms.
An adenocarcinoma arising from the appendix, characterized by the presence of signet-ring, mucin-producing malignant cells. The signet-ring cells constitute more than fifty-percent of the malignant cells.
A carcinoma that arises from the small intestine. It is characterized by the presence of malignant epithelial cells with vesicular nucleus, distinct nucleolus, and abundant pink cytoplasm.
Noninfectious, synthetic, virus-like particles (VLP) containing the major viral capsid protein, L1, of the human papillomavirus type 18 with potential immunoprotective activity. Vaccination with HPV 18 L1-VLP may stimulate the host immune system to mount cytotoxic T lymphocyte (CTL) response against cells positive for HPV 18, thereby preventing cervical infection upon exposure to HPV type 18.
A morphologic variant of papillary carcinoma of the thyroid gland that predominantly affects children. It is characterized by the presence of a solid growth pattern. The malignant cells have nuclear features that are characteristic of papillary carcinomas of the thyroid gland.
A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. E7080 blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=445461&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=445461&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48636"" NCI Thesaurus)
Diagnosis of celiac disease at a later age despite an asymptomatic clinical course. Serologic evidence with minimal histological changes in the intestinal mucosa are noted. The presence of human tissue transglutaminase, endomysial and gliadin antibodies without substantial villous changes follow many years of a seemingly gluten-tolerant diet. Despite an unremarkable clinical course, continued unrestricted gluten intake may predispose to the same sequelae as overt disease.
A change in the structure of the RET gene.
A squamous cell carcinoma that arises from the nasal cavity and is characterized by prominent production of keratin.
An adenocarcinoma arising from the rectosigmoid area. It is more frequently seen in populations with a Western type diet and in patients with a history of chronic inflammatory bowel disease. Signs and symptoms include intestinal bleeding, anemia, and change in bowel habits. According to the degree of cellular differentiation, rectosigmoid adenocarcinomas are divided into well, moderately, and poorly differentiated. Histologic variants include mucinous adenocarcinoma, signet ring cell carcinoma, medullary carcinoma, serrated adenocarcinoma, cribriform comedo-type adenocarcinoma, and micropapillary adenocarcinoma.
A hepatocellular carcinoma that occurs during adulthood and has recurred after a period of remission.
A morphologic variant of sarcomatoid carcinoma characterized by the presence of malignant glandular or squamous cells associated with malignant giant and spindle cells.
A synthetic peptide consisting of amino acid residues 614 through 622 of the melanoma-melanocyte antigen glycoprotein 100 (gp100). Vaccination with gp100:614-622 peptide may stimulate a cytotoxic T-cell immune response against tumor cells that express this antigen, resulting in decreased tumor growth and cell lysis. gp100 antigen is a self-antigen expressed by melanocytes, pigmented retinal cells and most melanoma lesions and recognized via class I and II HLA-restricted mechanisms.
A semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata radiolabeled with carbon 11 (11C) with antineoplastic and radiotracer properties. During the S phase of the cell cycle, topotecan inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. Quantitation of 11C topotecan accumulated in tumor tissues by positron emission tomography (PET) may help predict responses to topotecan therapy.
A drug used to help people stop smoking by acting the same way nicotine acts in the brain. It is a type of nicotine receptor partial agonist.
The hydrochloride salt form of fentanyl, a synthetic, lipophilic phenylpiperidine opioid agonist with analgesic and anesthetic properties. Fentanyl selectively binds to the mu-receptor in the central nervous system (CNS) thereby mimicking the effects of endogenous opiates. Stimulation of the mu-subtype opioid receptor stimulates the exchange of GTP for GDP on the G-protein complex and subsequently inhibits adenylate cyclase. This results in a decrease in intracellular cAMP and leads to a reduction in the release of neurotransmitters such as substance P, GABA, dopamine, acetylcholine and noradrenaline. The analgesic effect of fentanyl is likely due to its metabolite morphine, which induces opening of G-protein-coupled inwardly rectifying potassium (GIRK) channels and blocks the opening of N-type voltage-gated calcium channels, thereby resulting in hyperpolarization and reduced neuronal excitability.
The presence of malignant tubular formations which are thought to represent malignant counterparts of the terminal ductal-lobular units of the breast.
A tooth whose root canal system has been filled in three dimensions and where a surplus of material extrudes beyond the foramina.
A tooth whose root canal system has been inadequately obturated in any dimension, leaving large reservoirs for recontamination.
Clinical syndrome defined by the presence of both infection and a systemic inflammatory response that progresses to multi-organ failure.
Episodic ataxia type 1 (EA1) is a potassium channelopathy characterized by constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks individuals may experience a number of variable symptoms including vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing, among others. EA1 may be associated with epilepsy. Other possible associations include delayed motor development, cognitive disability, choreoathetosis, and carpal spasm. Usually, onset is in childhood or early adolescence.
Refractive error in which the vertical meridian is relatively hypermetropic and the horizontal meridian is relatively myopic (or ocular astigmatism in which the refractive power of the horizontal meridian is the greatest). [ORCID:0000-0003-0986-4123]
Thinning in the layers of the retina and retinal pigment epithelium around the optic nerve. [PMID:20920826]
A Burkitt lymphoma occurring in HIV-positive patients.
A human recombinant form of the naturally occurring human enzyme hyaluronidase with potential chemoadjuvant activity. Upon local administration, recombinant human hyaluronidase hydrolyzes hyaluronic acid, a glucosaminoglycan responsible for the viscosity of the interstitial barrier. The digestion of hyaluronic acid lowers the viscosity in the interstitial space, thereby increasing permeability and facilitating local penetration of chemotherapeutic agents into cancer cells.
A supranuclear gaze palsy is an inability to look in a particular direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.
Periodic spells of incoordination and imbalance, that is, episodes of ataxia typically lasting from 10 minutes to several hours or days.\n
Astigmatism with more plus power on the horizontal meridian. []
Episodic ataxia type 2 (EA2) is characterized by paroxysmal attacks of ataxia, vertigo, and nausea typically lasting minutes to days in duration. Attacks can be associated with dysarthria, diplopia, tinnitus, dystonia, hemiplegia, and headache. About 50% of individuals with EA2 have migraine headaches. Onset is typically in childhood or early adolescence (age range 2-32 years). Frequency of attacks can range from once or twice a year to three or four times a week. Attacks can be triggered by stress, exertion, caffeine, alcohol, fever, heat, and phenytoin; they can be stopped or decreased in frequency and severity by administration of acetazolamide or 4-aminopyridine. Between attacks, individuals may initially be asymptomatic but commonly develop interictal findings that can include nystagmus, pursuit and saccade alterations, and ataxia.
Deposits of various size, shape, consistency, refractive index, and motility within the eye's vitreous humour, which is normally transparent.
A morphologic variant of diffuse large B-cell lymphoma occurring in HIV-positive patients.
Edema/fluid accumulating between the retinal pigment epithelium and Bruch's membrane.
Substances that inhibit the SCHIZONTS stage of protozoa. There is particular interest in them as ANTIMALARIALS.
High doses of contraceptive substances that can be taken before, the morning after, or up to five days after the unprotected vaginal intercourse.
Pathological processes of the female URINARY TRACT, the reproductive system (GENITALIA, FEMALE), and disorders related to PREGNANCY.
Accumulation of clear fluid in the between the layers of membrane (tunica vaginalis) surrounding the testis.
A condition with abnormally low levels of PREBETA-LIPOPROTEINS in the blood.
The repeated weak excitation of brain structures, that progressively increases sensitivity to the same stimulation. Over time, this can lower the threshold required to trigger seizures.
An acute infection of the prostate gland caused by bacteria, most often Escherichia coli, Proteus mirabilis, Klebsiella, and Pseudomonas aeruginosa. Signs and symptoms include fever, lower back pain, urinary frequency, and painful urination. The urinalysis reveals the presence of white cells. Risk factors include intraprostatic ductal reflux, phimosis, urinary tract infections, and unprotected anal intercourse.
Inflammation of the prostate gland that is not associated with any symptoms. It is characterized by the presence of inflammatory cells in the prostatic fluid.
A chronic infection of the prostate gland caused by bacteria. It is manifested with recurring urinary tract infections. The culture of the prostatic fluid, semen, or post-massage urine specimen reveals the presence of bacteria.
Acute skin inflammatory reaction caused by drugs, especially chemotherapeutic agents, weeks or months following radiotherapy. The inflammatory reaction is confined to the previously irradiated skin and the symptoms disappear after the removal of the pharmacologic agent.
A type of mesangiocapillary glomerulonephritis that is characterized by subepithelial immune deposit and may be a variant of type I.
Sudden suspension of cardiac activity that is usually due to ARRHYTHMIA, in contrast to heart attack (MYOCARDIAL INFARCTION) which occurs due to blockage. The sudden suspension of cardiac activity generally requires RESUSCITATION.
Familial partial lipodystrophy type 1 (FPLD1), or Kobberling-type lipodystrophy, is characterized by loss of adipose tissue confined to the extremities, with normal or increased distribution of fat on the face, neck, and trunk (Kobberling and Dunnigan, 1986). For a general description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.
Familial partial lipodystrophy is a metabolic disorder characterized by abnormal subcutaneous adipose tissue distribution beginning in late childhood or early adult life. Affected individuals gradually lose fat from the upper and lower extremities and the gluteal and truncal regions, resulting in a muscular appearance with prominent superficial veins. In some patients, adipose tissue accumulates on the face and neck, causing a double chin, fat neck, or cushingoid appearance. Metabolic abnormalities include insulin-resistant diabetes mellitus with acanthosis nigricans and hypertriglyceridemia; hirsutism and menstrual abnormalities occur infrequently. Familial partial lipodystrophy may also be referred to as lipoatrophic diabetes mellitus, but the essential feature is loss of subcutaneous fat (review by Garg, 2004). The disorder may be misdiagnosed as Cushing disease (see 219080) (Kobberling and Dunnigan, 1986; Garg, 2004). Genetic Heterogeneity of Familial Partial Lipodystrophy Familial partial lipodystrophy is a clinically and genetically heterogeneous disorder. Types 1 and 2 were originally described as clinical subtypes: type 1 (FPLD1; 608600), characterized by loss of subcutaneous fat confined to the limbs (Kobberling et al., 1975), and FPLD2, characterized by loss of subcutaneous fat from the limbs and trunk (Dunnigan et al., 1974; Kobberling and Dunnigan, 1986). No genetic basis for FPLD1 has yet been delineated. FPLD3 (604367) is caused by mutation in the PPARG gene (601487) on chromosome 3p25; FPLD4 (613877) is caused by mutation in the PLIN1 gene (170290) on chromosome 15q26; FPLD5 (615238) is caused by mutation in the CIDEC gene (612120) on chromosome 3p25; FPLD6 (615980) is caused by mutation in the LIPE gene (151750) on chromosome 19q13; and FPLD7 (606721) is caused by mutation in the CAV1 gene (601047) on chromosome 7q31.
Pathological processes of the female URINARY TRACT and the reproductive system (GENITALIA, FEMALE).
Pathological processes of the male URINARY TRACT and the reproductive system (GENITALIA, MALE).
An attenuated vaccine used to prevent and/or treat HERPES ZOSTER, a disease caused by HUMAN HERPESVIRUS 3.
Inhaling liquid or solids, such as stomach contents, into the RESPIRATORY TRACT. When this causes severe lung damage, it is called ASPIRATION PNEUMONIA.
Interacting DNA-encoded regulatory subsystems in the GENOME that coordinate input from activator and repressor TRANSCRIPTION FACTORS during development, cell differentiation, or in response to environmental cues. The networks function to ultimately specify expression of particular sets of GENES for specific conditions, times, or locations.
Hyper-IgM syndrome type 2 (HIGM2) is a rare immunodeficiency characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
HIGM3, first described in humans by Ferrari et al. (2001), is characterized by hypogammaglobulinemia with normal or elevated levels of IgM. For a general phenotypic description and a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
An autosomal dominant form of ectodermal dysplasia which is due to mutations in the gene for the EDAR RECEPTOR.
A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.
A highly contagious parvovirus infection in mink, caused by MINK ENTERITIS VIRUS or the closely related FELINE PANLEUKOPENIA VIRUS or CANINE PARVOVIRUS. Transmission usually occurs by the fecal/oral route.
An autosomal dominant disorder that is manifested by thickened spongiform ORAL MUCOSA with a white opalescent tint. Other MUCOSAL TISSUE may also be involved mucosa found in the VAGINA; RECTUM, and NASAL CAVITY may be similarly involved. This form of LEUKOKERATOSIS can be caused by a mutation in the gene for KERATIN 4 and is not considered a PRENEOPLASTIC CONDITION.
Palmoplantar keratoderma (PPK) is a common hereditary cutaneous disorder characterized by marked hyperkeratosis on the surface of palms and soles (Hennies et al., 1995). PPK has been classified into diffuse, focal, and punctate forms according to the pattern of hyperkeratosis on the palms and soles (Lucker et al., 1994). Diffuse PPK develops at birth or shortly thereafter and involves the entire palm and sole with a sharp cutoff at an erythematous border; there are no lesions outside the volar skin, and, in particular, no follicular or oral lesions. In contrast, focal PPK is a late-onset form in which focal hyperkeratotic lesions develop in response to mechanical trauma; an important distinguishing feature is the presence of lesions at other body sites, e.g., oral and follicular hyperkeratosis (Stevens et al., 1996). Palmoplantar keratodermas can be further subdivided histologically into epidermolytic and nonepidermolytic PPK (Risk et al., 1994). Genetic Heterogeneity of Palmoplantar Keratoderma Nonepidermolytic palmoplantar keratoderma (NEPPK; 600962) is caused by mutation in the KRT1 gene. A focal form of NEPPK (FNEPPK1; 613000) is caused by mutation in the KRT16 gene (148067). Another focal form, FNEPPK2 (616400), is caused by mutation in the TRPV3 gene (607066); mutation in TRPV3 can also cause Olmsted syndrome (OLMS; 614594), a severe mutilating form of PPK. The diffuse Bothnian form of NEPPK (PPKB; 600231) is caused by mutation in the AQP5 gene (600442). The Nagashima type of nonepidermolytic diffuse PPK (PPKN; 615598) is caused by mutation in the SERPINB7 gene (603357). A generalized form of epidermolytic hyperkeratosis (EHK; 113800), also designated bullous congenital ichthyosiform erythroderma (BCIE), is caused by mutation in the keratin genes KRT1 and KRT10 (148080). For a discussion of punctate PPK, see 148600; for a discussion of striate PPK, see 148700.
A worldwide emerging disease of weaned piglets first recognized in swine herds in western Canada in 1997. This syndrome is characterized by progressive weight loss, rapid (tachypnea) and difficult (dyspnea) breathing, and yellowing of skin. PMWS is caused by PORCINE CIRCOVIRUS infection, specifically type 2 or PCV-2.
The presence of the following interrelated signs observed in active women and girls: low energy availability with or without disordered eating; menstrual dysfunction; low bone mineral density.
Compounds that contain benzimidazole joined to a 2-methylpyridine via a sulfoxide linkage. Several of the compounds in this class are ANTI-ULCER AGENTS that act by inhibiting the POTASSIUM HYDROGEN ATPASE found in the PROTON PUMP of GASTRIC PARIETAL CELLS.
The random catabolism of DNA accompaning the irreversible damage to tissue which leads to the pathological death of one or more cells.
A reaction that severs one of the covalent sugar-phosphate linkages between NUCLEOTIDES that compose the sugar phosphate backbone of DNA. It is catalyzed enzymatically, chemically or by radiation. Cleavage may be exonucleolytic - removing the end nucleotide, or endonucleolytic - splitting the strand in two.
Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.
Sets of enzymatic reactions occurring in organisms and that form biochemicals by making new covalent bonds.
Vaccines or candidate vaccines used to prevent PAPILLOMAVIRUS INFECTIONS. Human vaccines are intended to reduce the incidence of UTERINE CERVICAL NEOPLASMS, so they are sometimes considered a type of CANCER VACCINES. They are often composed of CAPSID PROTEINS, especially L1 protein, from various types of ALPHAPAPILLOMAVIRUS.
Interruptions in the sugar-phosphate backbone of DNA.
An agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic activity. Netoglitazone exerts both peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist activity. Netoglitazone decreases bone formation and increases marrow adipocyte formation in vivo.
A folate analogue inhibitor of dihydrofolate reductase (DHFR) exhibiting high affinity for reduced folate carrier-1 (RFC-1) with antineoplastic and immunosuppressive activities. Pralatrexate selectively enters cells expressing RFC-1; intracellularly, this agent is highly polyglutamylated and competes for the folate binding site of DHFR, blocking tetrahydrofolate synthesis, which may result in depletion of nucleotide precursors; inhibition of DNA, RNA and protein synthesis; and apoptotic tumor cell death. Efficient intracellular polyglutamylation of pralatrexate results in higher intracellular concentrations compared to non-polyglutamylated pralatrexate, which is more readily effuxed by the MRP (multidrug resistance protein) drug efflux pump. RFC-1, an oncofetal protein expressed at highest levels during embryonic development, may be over-expressed on the cell surfaces of various cancer cell types.
A recombinant fusion protein comprised of a human monoclonal antibody directed against the epithelial cell adhesion molecule (EpCAM or KS) linked to an active interleukin-2 (IL2) molecule with potential antineoplastic activity. Tucotuzumab Celmoleukin recognizes and binds to EpCAM, a cell surface epithelial protein that is expressed on a wide variety of cancer cells, thereby concentrating IL2 in EpCAM-expressing tumor tissue. Subsequently, the localized IL2 moiety of the fusion protein may stimulate a cytotoxic T-cell antitumor immune response.
An orally bioavailable aminopyrimidine-derivative Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity. Designed to overcome imatinib resistance, nilotinib binds to and stabilizes the inactive conformation of the kinase domain of the Abl protein of the Bcr-Abl fusion protein, resulting in the inhibition of the Bcr-Abl-mediated proliferation of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) cells. This agent also inhibits the receptor tyrosine kinases platelet-derived growth factor receptor (PDGF-R) and c-kit, a receptor tyrosine kinase mutated and constitutively activated in most gastrointestinal stromal tumors (GISTs). With a binding mode that is energetically more favorable than that of imatinib, nilotinib has been shown to have an approximately 20-fold increased potency in kinase and proliferation assays compared to imatinib.
An orally available, s-triazine derivative, ATP-competitive phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor ZSTK474 inhibits all four PI3K isoforms. Inhibiting the activation of the PI3K/AKT kinase (or protein kinase B) signaling pathway results in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents. This agent does not induce apoptosis but rather induces strong G(0)/G(1) arrest, which might contribute to its favorable efficacy in tumor cells.
A fully human monoclonal agonistic antibody directed against tumor necrosis factor-alpha (TNF-alpha)-related apoptosis-inducing ligand receptor-2 (TRAIL-R2) with potential antitumor activity. Mimicking the natural ligand TRAIL, lexatumumab binds to and activates TRAIL-R2, which may trigger apoptosis in and inhibit the growth of TRAIL-R2-expressing tumor cells. TRAIL-R2, also known as death receptor 5 (DR5), is a member of the TNF receptor family and is expressed on many malignant cell types.
A recombinant, bivalent, human papillomavirus (HPV) vaccine, containing virus-like particles for HPV types 16 and 18 linked to the adjuvant ASO4, with potential immunoprotective and antineoplastic properties. Upon administration, HPV 16/18 L1 virus-like particle/ASO4 vaccine may generate humoral and cellular immunity against HPV types-16 and -18 antigens, thereby preventing cervical infection upon exposure to HPV types 16 and 18. In addition, this agent may stimulate an antitumoral cellular immune response against cervical cancer associated with HPV infection.
An immunoradioconjugate containing metuximab, an antibody fragment targeting the hepatocellular cancer (HCC)-associated antigen HAb18G/CD147, that is conjugated to the radioisotope iodine I 131, with potential antineoplastic activity. Upon administration, the metuximab moiety of licartin targets and binds to HAb18G/CD147 on HCC cells; upon internalization, the radioisotope I 131 delivers a cytotoxic dose of gamma radiation, thereby causing selective destruction of HAb18G/CD147-expressing cells. HAb18G/CD147, a member of CD147 family, is overexpressed in HCC and fibroblasts and its expression is associated with cancer cell progression and increased adhesion, invasion and metastasis.
A water-soluble and biodegradable polymer naturally synthesized by various strains of Bacillus and composed of D- and L-glutamic acid polymerized via gamma-amide linkages, with potential antineoplastic activity. Upon administration, poly-gamma glutamic acid may augment the immune response by increasing the production of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) and inducing the activation of macrophage and natural killer (NK) cells. IFN-gamma is a major mediator of innate and adaptive immunity against viral and intracellular bacterial infections as well as for tumor control. TNF-alpha is a cytokine involved in systemic inflammation, which is capable of inducing apoptotic cell death and exhibits anti-tumoral effects.
A murine monoclonal antibody with two antigen-recognition sites: one for CD3, an antigen expressed on mature T cells, and one for HER-2-neu, a tumor-associated antigen that promotes tumor growth. Ertumaxomab attaches to CD3-expressing T cells and HER-2-neu-expressing tumor cells, selectively cross-linking tumor and immunologic cells which results in the recruitment of cytotoxic T cells to the T cell/tumor cell aggregate.
A fully human IgG1 monoclonal antibody directed against B-Lymphocyte stimulator protein (BlyS or TNFSF13B) with potential immunomodulating activity. Belimumab specifically recognizes and inhibits the biological activity of BlyS, thereby preventing the binding of BlyS to B-lymphocytes. This inhibits the maturation of B-lymphocytes and may induce apoptosis in B-lymphocytes. In addition, it may decrease B-lymphocyte proliferation and/or survival. BlyS, a member of TNF family supporting B-lymphocyte maturation and survival, has been implicated in the pathogenesis of autoimmune diseases and B-lymphocyte malignancies.
A tyrosyl-based arylsulfonamide inhibitor of human immunodeficiency virus (HIV) protease.
A metered dose inhaler formulation of fluticasone-salmeterol drug combination.
Delayed acquisition of age appropriate motor milestones that produce small and precise movements.
VACTERL association is a disorder that affects many body systems. VACTERL stands for vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. People diagnosed with VACTERL association typically have at least three of these characteristic features. Affected individuals may have additional abnormalities that are not among the characteristic features of VACTERL association.Defects in the bones of the spine (vertebrae) are present in 60 to 80 percent of people with VACTERL association. These defects may include misshapen vertebrae, fused vertebrae, and missing or extra vertebrae. In some people, spinal problems require surgery or cause health problems, such as back pain of varying severity, throughout life. Sixty to 90 percent of individuals with VACTERL association have narrowing or blockage of the anus (anal atresia). Anal atresia may be accompanied by abnormalities of the genitalia and urinary tract (genitourinary anomalies). Heart (cardiac) defects occur in 40 to 80 percent of individuals with VACTERL association. Cardiac defects can range in severity from a life-threatening problem to a subtle defect that does not cause health problems. Fifty to 80 percent of people with VACTERL association have a tracheo-esophageal fistula, which is an abnormal connection (fistula) between the esophagus and the windpipe (trachea). Tracheo-esophageal fistula can cause problems with breathing and feeding early in life and typically requires surgical correction in infancy. Kidney (renal) anomalies occur in 50 to 80 percent of individuals with VACTERL association. Affected individuals may be missing one or both kidneys or have abnormally developed or misshapen kidneys, which can affect kidney function. Limb abnormalities are seen in 40 to 50 percent of people with VACTERL association. These abnormalities most commonly include poorly developed or missing thumbs or underdeveloped forearms and hands.Some of the features of VACTERL association can be subtle and are not identified until late in childhood or adulthood, making diagnosis of this condition difficult.
A congenital coronary vessel anomaly in which the left main CORONARY ARTERY originates from the PULMONARY ARTERY instead of from AORTA. The congenital heart defect typically results in coronary artery FISTULA; LEFT-SIDED HEART FAILURE and MITRAL VALVE INSUFFICIENCY during the first months of life.
Repeated episodes of the formation of a blot clot in a deep vein.
Longstanding abnormal acid accumulation or depletion of base.
Polyneuropathy associated with IgM monoclonal gammapathy (MG) with anti-MAG (myelin-associated-glycoprotein) activity is a demyelinating polyneuropathy characterized clinically by sensory ataxia, tremor, paresthesia, and impaired gait.
Increased susceptibility to mycobacterial avium complex infections, as manifested by recurrent episodes of mycobacterial infection.
An orally bioavailable receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Linifanib inhibits members of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor families; it exhibits much less activity against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. This agent does not have a general antiproliferative effect due to its high dose requirement. However, linifanib may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases, such as FMS-related tyrosine kinase receptor-3 (FLT3).
An orally bioavailable nonsteroidal anti-inflammatory agent (NSAID) with potential antiangiogenic and antineoplastic activities. Apricoxib binds to and inhibits the enzyme cyclooxygenase-2 (COX-2), thereby inhibiting the conversion of arachidonic acid into prostaglandins. Apricoxib-mediated inhibition of COX-2 may induce tumor cell apoptosis and inhibit tumor cell proliferation and tumor angiogenesis. COX-related metabolic pathways may represent crucial regulators of cellular proliferation and angiogenesis.
An orally bioavailable, synthetic tripeptide inhibitor of the nonstructural protein 3 and 4A complex (NS3/NS4A), with potential activity against hepatitis C virus (HCV) genotype 1. Upon administration, boceprevir reversibly binds to the active center of the HCV NS3/NS4A and prevents NS3/NS4A protease-mediated polyprotein maturation. This disrupts the processing of viral proteins and the formation of a viral replication complex, which inhibits viral replication in HCV genotrype 1-infected host cells. NS3, a serine protease, is essential for the proteolytic cleavages within the HCV polyprotein and plays a key role during HCV viral RNA replication. NS4A is an activating factor for NS3. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family.
A T-cell immunostimulatory factor derived from the soluble form of lymphocyte-activation gene 3 (LAG-3) protein with potential antineoplastic activity. Upon administration, alone or in combination with tumor antigens, IMP321 binds, with high affinity, to MHC class II molecules expressed by dendritic cells (DC), which may result in DC maturation, DC migration to lymph nodes, enhanced DC cross-presentation of antigens to T cells, and antitumor cytotoxic T cell responses. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=496939&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=496939&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C62509"" NCI Thesaurus)
Botulism that is caused by consuming food or beverage that contains the botulinum toxin.
Congenital urachal anomaly (CUA) describes a group of urachal remnants, found more frequently in males than females, that result from incomplete closure of the urachus (an embryological remnant of the allantois) during prenatal development, and that are usually asymptomatic (and found as an incidental finding on a radiological study) but can also present with umbilical discharge (in patent urachus or urachal sinus), infraumblical mass and pain, or with complications such as obstruction and infection. CUAs include patent urachus, urachal sinus, urachal cyst and urachal diverticulum (see these terms).
Autoimmune diabetes in adults with slowly progressive PANCREATIC BETA CELL failure and the presence of circulating autoantibodies to PANCREATIC ISLETS cell antigens.
An acute inflammation of a synovial membrane. It is associated with swelling and pain in the affected area.
A form of acromelic dysplasia with the distinctive radiological sign of angel-shaped middle phalanges, a typical metacarpophalangeal pattern profile (mainly affecting first metacarpals and middle phalanges of second, third and fifth digits which all appear short), epiphyseal changes in the hips and in some, abnormal dentition and delayed bone age. A rare disease with less than 20 cases reported in the literature, however, it is likely under diagnosed. Caused by mutations in the growth differentiation factor 5 (GDF5) gene, located on chromosome 20q11.2, encoding CDMP1 (cartilage derived morphogenetic protein). CDMP1 belongs to the TGF beta super family and plays a role in bone growth and joint morphogenesis. Transmitted as an autosomal dominant condition.
Remaining collapsed and obliterated urachal tissue between the bladder dome and umbilicus.
A rare disorder characterized by transient left ventricular wall systolic dysfunction, resulting in apical ballooning appearance, chest pain, and ST segment elevation.
A transforming growth factor beta2 (TGF-beta2) antisense gene-modified allogeneic tumor cell vaccine with potential immunostimulatory and antineoplastic activities. Belagenpumatucel-L is prepared by transfecting allogeneic non-small cell lung cancer (NSCLC) cells with a plasmid containing a TGF-beta2 antisense transgene, expanding the cells, and then irradiating and freezing them. Upon administration, this agent may elicit a cytotoxic T lymphocyte (CTL) response against host NSCLC cells, resulting in decreased tumor cell proliferation; vaccine immunogenicity may be potentiated by suppression of tumor TGF-beta2 production by antisense RNA expressed by the vaccine plasmid TGF-beta2 antisense transgene. Elevated levels of TGF-beta2 are frequently linked to immunosuppression in cancer patients and may be inversely correlated with prognosis in patients with NSCLC.
A morpholine and thiophene derivative that functions as a FACTOR XA INHIBITOR and is used in the treatment and prevention of DEEP-VEIN THROMBOSIS and PULMONARY EMBOLISM. It is also used for the prevention of STROKE and systemic embolization in patients with non-valvular ATRIAL FIBRILLATION, and for the prevention of atherothrombotic events in patients after an ACUTE CORONARY SYNDROME.
A dextroamphetamine drug precursor that also functions as a CENTRAL NERVOUS SYSTEM STIMULANT and DOPAMINE UPTAKE INHIBITOR and is used in the treatment of ATTENTION DEFICIT HYPERACTIVITY DISORDER.
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Height greater than two standard deviations below the mean for the age and sex of the reference population.
A recombinant human IgG1 monoclonal antibody (MoAb) directed against the tumor associated antigen (TAA) epithelial cell adhesion molecule (EpCAM) with potential antitumor activity. Adecatumumab binds to EpCAM, which may result in antibody-dependent cellular cytotoxicity (ADCC) directed against EpCAM-expressing tumor cells. EpCAM (CD326), a cell surface protein upregulated on many tumor cell types, promotes the proliferation, migration and invasiveness of tumor cells; for some cancers, overexpression has been correlated with decreased survival.
A prodrug form of the acyclic guanosine derivative omaciclovir with activity against varicella zoster virus (VZV) and other members of the herpesvirus family. Valomaciclovir is converted in vivo to omaciclovir, a nucleoside analog inhibitor of VZV DNA polymerase.
A benzenesulfonamide derivative with vasodilatory activity. Udenafil selectively inhibits phosphodiesterase type 5 (PDE5), thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa and corpus spongiosum of the penis; inhibition of cGMP degradation results in prolonged muscle relaxation, vasodilation, and blood engorgement of the corpus cavernosa, and, so, prolonged penile erection. This agent does not significantly inhibit the PDE11 isozyme; PDE11 inhibition may be associated with significant myalgia.
A cyclohexanol and phenol derivative and metabolite of venlafaxine that functions as a SEROTONIN AND NORADRENALINE REUPTAKE INHIBITOR (SNRI) and is used as an ANTIDEPRESSIVE AGENT.
A small-molecule inhibitor of heat shock protein 90 (HSP90) with antiproliferative and antineoplastic activities. Retaspimycin binds to and inhibits the cytosolic chaperone functions of HSP90, which maintains the stability and functional shape of many oncogenic signaling proteins and may be overexpressed or overactive in tumor cells. Retaspimycin-mediated inhibition of HSP90 promotes the proteasomal degradation of oncogenic signaling proteins in susceptible tumor cell populations, which may result in the induction of apoptosis.
A cytidine analogue and nucleoside reverse transcriptase inhibitor (NRTI) with anti-HIV activity. Apricitabine is effective against nucleoside-resistant HIV.
A 26-base guanine-rich oligodeoxynucleotide aptamer with potential apoptotic induction activity. Upon administration, anti-nucleolin aptamer AS1411 targets and binds to nucleolin, a nucleolar phosphoprotein which is overexpressed on the surface of certain cancer cells. Via binding to cell surface nucleolin, AS1411 is internalized and may prevent nucleolin from binding to and stabilizing mRNA of the anti-apoptotic BCL2, thereby destabilizing BCL2 mRNA, leading to a reduction in BCL2 protein synthesis. This may lead to the induction of apoptosis.
The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFFD3 is an autosomal recessive disorder characterized by bitemporal skin lesions with variable facial findings, including thin and puckered periorbital skin, distichiasis and/or absent eyelashes, upslanting palpebral fissures, a flat nasal bridge with a broad nasal tip, large lips, and redundant facial skin (summary by Slavotinek et al., 2013). FFDD2 (614973) is characterized by the same facial features as FFDD3, but the inheritance is autosomal dominant. For a classification and a discussion of genetic heterogeneity of FFDD, see FFDD1 (136500).
Malignant epithelial neoplasm arising from the tracheal mucosa.
The proteasome is a protein-destroying apparatus involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. It is capable of degrading a variety of cellular proteins in a rapid and timely fashion and most substrate proteins are modified by ubiquitin before their degradation by the proteasome. The proteasome is a large protein complex consisting of a proteolytic core called the 20S particle and ancillary factors that regulate its activity in various ways. The most common form is the 26S proteasome containing one 20S core particle and two 19S regulatory particles that enable the proteasome to degrade ubiquitinated proteins by an ATP-dependent mechanism. Another form is the immunoproteasome containing two 11S regulatory particles, PA28 alpha and PA28 beta, which are induced by interferon gamma under the conditions of intensified immune response. Other regulatory particles include PA28 gamma and PA200. Although PA28 gamma also belongs to a family of activators of the 20S proteasome, it is localized within the nucleus and forms a homoheptamer. PA28 gamma has been implicated in the regulation of cell cycle progression and apoptosis. PA200 has been identified as a large nuclear protein that stimulates proteasomal hydrolysis of peptides.
Inflammation of the lungs due to the inhalation of solid or liquid material.
Dilatation of the blood vessels of the conjunctiva leading to a red appearance of the sclera.
The orally available hydrochloride salt of pyrrolidine-3-carboxylic acid with potential antineoplastic activity. As a selective antagonist of the endothelin-A (ETA) receptor, atrasentan binds selectively to the ETA receptor, which may result in inhibition of endothelin-induced angiogenesis and tumor cell proliferation.
The hydrochloride salt of enzastaurin, a synthetic macrocyclic bisindolemaleimide with potential antineoplastic activity. Binding to the ATP-binding site, enzastaurin selectively inhibits protein kinase C beta, an enzyme involved in the induction of vascular endothelial growth factor (VEGF)-stimulated neo-angiogenesis. This agent may decrease tumor blood supply and so tumor burden.
An antimetabolite analogue of aminopterin with potential antineoplastic activity. As a folate antagonist, talotrexin binds to and inhibits the function of dihydrofolate reductase, resulting in the inhibition of folate metabolism, DNA synthesis, and cell division. Hydrosoluble, talotrexin is actively transported into cells by the reduced folate carrier (RFC) and, therefore, is unlikely to be associated with P-glycoprotein-mediated multidrug resistance.
Familial pulmonary fibrosis (FPF in this GeneReview) is defined as idiopathic interstitial pneumonia (IIP) in two or more first-degree relatives (parent, sib, or offspring). Up to 20% of cases of IIP cluster in families. The clinical findings of IIP are bibasilar reticular abnormalities, ground glass opacities, or diffuse nodular lesions on high-resolution computed tomography and abnormal pulmonary function studies that include evidence of restriction (reduced VC with an increase in FEV1/FVC ratio) and/or impaired gas exchange (increased P(A-a)O2 with rest or exercise or decreased diffusion capacity of the lung for carbon monoxide [DLCO]). FPF usually presents between ages 50 and 70 years. FPF may be complicated by lung cancer; bronchoalveolar cell carcinoma, small-cell carcinoma, and adenocarcinoma have been described.
Duplication of the long arm of chromosome 5 with a variable clinical picture consisting of psychomotor retardation and craniofacial, cardiovascular, musculoskeletal, and other anomalies.
Summitt syndrome is an extremely rare disorder originally described in two brothers and with characteristics of mild to severe craniosynostosis and syndactyly, obesity and normal intelligence. Acrocephaly, brachydactyly, clinodactyly, mild syndactyly of the hands and feet, genu valgum and marked obesity were later described in another patient. There have been no further descriptions in the literature since 1979.
The oil extracted from the cloves of Allium sativum. Garlic oil is used as a flavoring and is also reported to treat high blood pressure, high cholesterol, and diseases of the circulatory system.
Increased concentration of protein in the cerebrospinal fluid.
A combination preparation containing sodium bicarbonate, aspirin and citric acid, with analgesic and acid neutralizing properties. Sodium bicarbonate and citric acid provide rapid dissolution of aspirin in water. Sodium bicarbonate also neutralizes stomach acid. Aspirin, a salicylate, binds to and blocks the activities of cyclooxygenases thereby exerting analgesic, antipyretic and anti-inflammatory effects. This preparation is used to relief pain associated with stomach acid.
A hereditary condition caused by calcium sensing receptor gene mutations, resulting in calcium-hyposensitivity, and compensatory hypercalcemia and hypocalciuria.
Signal molecules that are involved in the control of cell growth and differentiation.
The tartrate salt of arformoterol, the (R,R)-enantiomer of formoterol and a long-acting beta-2 adrenergic agonist with bronchodilator activity. Arformoterol selectively binds to and activates beta-2 adrenergic receptors in bronchiolar smooth muscle, thereby causing stimulation of adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased intracellular cAMP levels cause relaxation of bronchial smooth muscle and lead to an inhibition of release of inflammatory mediators from mast cells. This may eventually lead to an improvement of airway function.
The phosphate salt form of carvedilol, a racemic mixture and adrenergic blocking agent with antihypertensive activity and devoid of intrinsic sympathomimetic activity. The S enantiomer of carvedilol nonselectively binds to and blocks beta-adrenergic receptors, thereby exerting negative inotropic and chronotropic effects, and leading to a reduction in cardiac output. In addition, both enantiomers of carvedilol bind to and block alpha 1-adrenergic receptors, thereby causing vasodilation and reducing peripheral vascular resistance.
The essential oil of Anethum graveolens. Dill weed oil is used as treatment for digestive complaints.
A sterile, lyophilized preparation of the Oka/Merck strain of the live, attenuated varicella-zoster virus (VZV), that can be used to prevent varicella, commonly known as chickenpox, or herpes zoster (HZ), commonly known as shingles. Upon reconstitution and subcutaneous vaccination with the VZV strain Oka/Merck live antigen, this vaccine induces antigen-specific T-cell and B-cell immune responses against the VZV, thereby protecting against VZV infection.
Any series of molecular signals generated as a consequence of binding to a toll-like receptor. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate innate immune response. [GO_REF:0000022, GOC:add, GOC:mtg_15nov05, ISBN:0781735149, PMID:12467241, PMID:12524386, PMID:12855817, PMID:15585605, PMID:15728447]
The chemical reactions and pathways involving linoleic acid, an unsaturated omega-6 fatty acid that has the molecular formula C18H32O2. [Wikipedia:Linoleic_Acid]
A hypersensitivity reaction mediated by antibodies formed against cell surface antigens.
Disordered thermoregulation characterized by an impaired ability to maintain a balance between heat production and heat loss, with resulting instability of body temperature.
Inability to achieve a full feeding volume.
The ratio of WAIST CIRCUMFERENCE to BODY HEIGHT.
Feelings of being unimportant or useless.
A relationship bound by mutual interests or loyalties.
A pattern of ease, relief, and transcendence in physical, psychospiritual, environmental, and/or social dimensions, which can be strengthened.
Compounds that suppress the degradation of INCRETINS by blocking the action of DIPEPTIDYL-PEPTIDASE IV. This helps to correct the defective INSULIN and GLUCAGON secretion characteristic of TYPE 2 DIABETES MELLITUS by stimulating insulin secretion and suppressing glucagon release.
A unilateral form of atrophy of the kidney.
Yellow-white intraretinal deposits in the macula typically associated with damaged outer blood-retina barrier and exudation of serous fluid and lipids from the retinal microvasculature. [ORCID:0000-0003-0986-4123]
Only part of the septum pellucidum (a thin, triangular, vertical membrane separating the lateral ventricles of the brain) is present. This feature can be appreciated on magnetic resonance tomography or computed tomography of the brain.
Extensively drug resistant TB are strains of TB that are resistant to at least rifampicin and isoniazid, and also resistant to a fluoroquinolone and to at least one of the three injectable TB drugs, capreomycin, kanamycin and amikacin.
Susceptible to reversible disturbances of consciousness, attention, cognition and perception that develop over a short period of time, which may compromise health.
A pattern of performing activities for oneself to meet health-related goals, which can be strengthened.
A pattern of participating knowingly in change for well-being, which can be strengthened.
A larger than usual distance between the left and right nipple.
Recurring actions that are often non-purposeful.
Excessive amounts and types of demands that require action.
A pattern of expectations and desires for mobilizing energy on one's own behalf, which can be strengthened.
An acyclic state that resembles PREGNANCY in that there is no ovarian cycle, ESTROUS CYCLE, or MENSTRUAL CYCLE. Unlike pregnancy, there is no EMBRYO IMPLANTATION. Pseudopregnancy can be experimentally induced to form DECIDUOMA in the UTERUS.
The presence of Neurofibromas in the subcutis.
A primary or metastatic malignant neoplasm that affects the eyelid.
A radioconjugate consisting of a lipophilic copper(II)bis(thiosemicarbazone) labeled with the positron- and beta-emitting isotope (64)Cu with hypoxia-selective and antineoplastic activities. With a high membrane permeability and redox potential, copper Cu 64-ATSM is preferentially taken up by hypoxic cells compared to normoxic cells; the extent of retention in tissue is inversely related to the state of tissue oxygenation allowing the quantitation of tissue hypoxia by positron emission tomography (PET). In addition, the radioactive copper moiety of this agent may deliver a selective cytotoxic dose of beta radiation to hypoxic tumor cells.
Potential for unstable blood glucose levels providing a susceptibility to comprised health status.
Benign concentric annular macular dystrophy (BCAMD) is initially characterized by parafoveal hypopigmentation and good visual acuity, but progresses to a retinitis pigmentosa (RP)-like phenotype with a bull's eye configuration (van Lith-Verhoeven et al., 2004).
A group of rare skeletal muscle ion-channel disorders caused by genetic mutations in the sodium and chloride channel genes. It is characterized by altered membrane excitability resulting in skeletal muscle stiffness. This group of myotonias is distinct from myotonic dystrophy because of the absence of systemic features or progressive weakness.
A pattern of choosing a course of action for meeting short- and long-term health-related goals, which can be strengthened.
A benign bone-forming neoplasm arising from the skull.
A rare autosomal recessive inherited disorder caused by mutations in the CPT1A gene. It is characterized by the presence of defective carnitine palmitoyltransferase 1A which is involved in fatty acid oxidation. Signs and symptoms may be exacerbated during fasting and include hypoketotic hypoglycemia, increased levels of carnitine in the blood, hepatomegaly, seizures, and coma.
The act of bending one's back forward from the waist on down.
Below normal weather temperatures that may lead to serious health problems. Extreme cold is a dangerous situation that can bring on health emergencies in susceptible people.
High temperature weather exceeding the average and of several weeks duration. Extreme heat is a dangerous situation that can bring on health emergencies in susceptible people.
A recombinant peptide similar to or identical to endogenous human cytokine interleukin-21 (IL-21) with potential antineoplastic activity. Denenicokin binds to and activates IL-21 receptors, expressed on T-cells, B-cells, dendritic cells (DC), and natural killer (NK) cells, modulating the proliferation and/or differentiation of T and B cells, promoting T cell survival, and increasing the cytolytic activity of cytotoxic T lymphocytes (CTLs) and NK cells.
A small synthetic molecule of triazolopyrimidine derivative with potential antitumor activity. With a novel mechanism of action distinct from the action of other vinca alkaloid compounds, TTI-237 specifically binds to tubulin at the vinca site, and promotes the polymerization of tubulin into microtubules. TTI-237 stabilizes tubulin and inhibits microtubule disassembly. This results in cell cycle arrest at the G2/M phase, and leading to cell death.
An extremely rare, benign or malignant mesenchymal tumor arising from the soft tissues. It is a distinctive tumor, which usually displays the following morphologic characteristics: low cellularity, myxoid changes, presence of spindled cells and osteoclasts, hemangiopericytoma-like vessels, hemorrhage, and osteoid-like matrix. It is associated with the presence of a paraneoplastic syndrome called osteogenic osteomalacia. This syndrome usually precedes the appearance of the tumor, and it is characterized by phosphaturia, hypophosphatemia, normal serum calcium levels, and decreased levels of 1,25-dihydroxyvitamin D3. Patients present with bone and muscle pain, severe muscle weakness, fractures, gait disturbances, skeletal deformity, height loss, and slow growth. The metabolic disturbances improve or completely disappear after the complete resection of the tumor.
A 24-base phosphorothiolate antisense oligodeoxynucleotide (ODN) for the proto-oncogene c-myb with potential antineoplastic activity. C-myb antisense oligonucleotide G4460 binds to codon sequences 2 to 9 of c-myb mRNA, inhibiting translation of the transcript. Suppression of c-myb expression with this agent may result in the restoration of normal differentiation pathways, increased antiproliferative effects, and the induction of apoptosis in early progenitor hematopoietic cells and in tumor cells that overexpress c-myb. Tumor-cell overexpression of c-myb blocks differentiation, promotes proliferation, and inhibits apoptosis.
A replication incompetent adenovirus encoding human pro-inflammatory cytokine interleukin-12 (IL-12) (Ad.hIL-12), with potential immunomodulating and antineoplastic activities. Upon intratumoral administration, the adenovirus selectively infects and replicates in tumor cells, which may result in tumor cell lysis. Synergistically, IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma and inducing cytotoxic T cell responses against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation.
An allogeneic vaccine consisting of Hodgkin lymphoma cells transfected with the granulocyte macrophage-colony-stimulating factor (GM-CSF) gene with potential antineoplastic activity. Upon vaccination, Hodgkin antigens-GM-CSF-expressing cell vaccine may stimulate a cytotoxic T-lymphocyte (CTL) immune response against Hodgkin lymphoma-associated antigens, which may result in the lysis of tumor cells expressing these antigens. In addition, transfected Hodgkin lymphoma cells secrete GM-CSF, which may potentiate the CTL response against Hodgkin lymphoma-associated antigens.
The non-glycosylated recombinant interferon alpha, subtype 1b, with immunostimulatory and antineoplastic activities. Alpha interferon-1b binds to specific cell-surface receptors, resulting in the transcription and translation of genes whose protein products mediate antiviral, antiproliferative, anticancer, and immune-modulating effects.
A recombinant, bispecific, single-chain antibody directed against both the T-cell surface-associated costimulatory molecule CD28 and a melanoma-associated proteoglycan (MAPG) with potential antitumor activity. By targeting both CD28 and MAPG, recombinant bispecific single-chain antibody rM28 enhances cytotoxic T-cell recognition of melanoma cells, which may result in immune effector cell-mediated tumor cell death and a decrease in distant metastases. This agent appears to have a long serum half-life secondary to the formation of dimers. When activated, CD28 facilitates interactions between T-cells and other immune effector cells resulting in cytotoxic T-lymphocyte responses; MAPG is a surface antigen expressed on the majority of melanomas, including primary cutaneous, ocular, and metastatic melanomas.
A synthetic quinolone derivative and dual kinase inhibitor that targets both Abl and Src kinases with potential antineoplastic activity. Unlike imatinib, bosutinib inhibits the autophosphorylation of both Abl and Src kinases, resulting in inhibition of cell growth and apoptosis. Because of the dual mechanism of action, this agent may have activity in resistant CML disease, other myeloid malignancies and solid tumors. Abl kinase is upregulated in the presence of the abnormal Bcr-abl fusion protein which is commonly associated with chronic myeloid leukemia (CML). Overexpression of specific Src kinases is also associated with the imatinib-resistant CML phenotype.
Side effects of cancer treatment received during adulthood occurring a long time after the treatment was completed.
Performance status defined as poor according to the ECOG performance score or Karnofsky performance score.
A low-fucose, human-mouse chimeric IgG1 monoclonal antibody with potential antineoplastic activity targeting at the ganglioside GD3, a surface antigen expressed on many malignant melanoma cells. Monoclonal antibody KW-2871 binds to GD3-positive cells, thereby initiating antibody-dependent cytotoxicity against GD3-positive cells. This agent is prepared by fusing murine immunoglobulin (Ig) light and heavy variable regions derived from the murine IgG3 antibody KM-641 to a human constant (Fc) region. The low fucose content of the oligosaccharide side chains of this antibody may enhance binding of the antibody Fc region to lymphocyte Fc receptors.
A sterile aqueous complex of polynuclear iron (III)-hydroxide in sucrose for intravenous use. Following intravenous administration, iron sucrose is dissociated by the reticuloendothelial system into iron and sucrose; the sucrose component is eliminated mainly by urinary excretion. Iron sucrose can be administered with or without erythropoietin to raise hemoglobin levels and may be used in cases of oral iron therapy intolerance or ineffectiveness. Hypersensitivity reactions are less common with iron sucrose compared to other parenteral iron products, such as iron dextran.
An orally bioavailable powder formulation of a synthetic phenylretinamide analogue of retinol with potential chemopreventive and antineoplastic activities. Fenretinide binds to and activates retinoic acid receptors (RARs), thereby inducing cell differentiation and apoptosis in some tumor cell types, including those of the colon, breast, prostate, and neuroblastoma. Independent of RAR activation, this agent also modulates gene expression that leads to ceramide-induced, caspase-independent programmed cell death (PCD) via effectors such as ganglioside GD3 and reactive oxygen species (ROS). Compared to the capsule form, the powder contains a mixture of wheat flour, fats, and sugar that may contribute to the enhanced bioavailability of fenretinide.
A plasmid DNA cancer vaccine encoding the intracellular domain (ICD) of the HER-2/neu proto-oncogene. Upon administration and after cellular uptake by skin or muscle cells, the pNGVL3-hICD vaccine plasmid expresses the HER-2/neu protein, which, after intracellular processing, may elicit both antigen-specific cytotoxic T-lymphocyte (CTL) and humoral immune responses against tumor cells expressing HER-2. The HER-2/neu ICD protein is highly immunogenic and, as a subdominant epitope, may be associated with decreased immune tolerance.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) transduced with a replication-deficient adenovirus vector encoding HER-2 with potential antineoplastic activity. Upon administration, adenovirus HER2-transduced autologous dendritic cell vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against HER-2-positive tumor cells, which may result in tumor cell death and decreased tumor growth. HER-2, a tyrosine kinase receptor for epidermal growth factor (EGF) (also known as neu and ErbB2), is overexpressed by some breast, ovarian, and gastric cancers.
A synthetic small-molecule inhibitor of checkpoint kinases 1 and 2 (Chk1 and Chk2) with potential antineoplastic activity. XL844 binds to and inhibits Chks 1 and 2, resulting in inhibition of cell cycle arrest, progressive DNA damage, inhibition of DNA repair, and, ultimately, tumor cell apoptosis. This agent also inhibits vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 3 (VEGFR3), important mediators of tumor angiogenesis and lymphogenesis, respectively. In the presence of extensive damage or absence of timely repair, these checkpoint-signaling pathways may also trigger a pathway that effects apoptosis. Normal functions of Chks involve the initiation of cell-cycle arrest and the up-regulation of transcription genes involved with DNA excision repair and dNTP synthesis.
A cell-based vaccine composed of allogeneic dendritic cells pulsed ex-vivo with an autologous myeloma idiotype with potential antineoplastic activity. Upon administration, allogeneic dendritic cell-myeloma idiotype vaccine may stimulate the host immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against myeloma cells, resulting in cell lysis.
A synthetic peripheral sigma receptor ligand with immunomodulatory and potential antitumor activities. Although the exact mechanism by which SR31747A exerts its antitumor effects has not been fully established, SR31747A binds to and inhibits the sigma1 receptor (SR31747A-binding protein-1 or SR-BP1), human sterol isomerase (emopamil-binding protein) and the sigma2 receptor, which may result in a reduction in tumor cell proliferation and tumor cell apoptosis. In addition, this agent inhibits the production of pro-inflammatory cytokines while increasing anti-inflammatory cytokines. Upregulated in various cancers, the sigma1 and sigma2 receptors and human sterol isomerase are proteins that are involved in the regulation of cell proliferation and survival.
A sterically stabilized, pegylated liposomal formulation containing CKD602, a semi-synthetic analogue of campthotecin with potential antitumor activity. CKD602 inhibits the action of topoisomerase I, an enzyme that produces reversible single-strand breaks in DNA during DNA replication. CDK602 stabilizes the topoisomerase I and DNA complex, thereby prevents religation of DNA breaks. This leads to an inhibition of DNA replication and triggers apoptotic cell death. The polyethylene glycol coating of S-CKD602 allows for greater plasma circulation time, thereby enhancing the concentration of CKD602 at the tumor site. Encapsulation of CKD602 preserves the active lactone form leading to an increased cytotoxic effect of CKD602. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=471934&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=471934&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61437"" NCI Thesaurus)
A pegylated, cross-linked, humanized divalent-Fab' antibody fragment directed against vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antiangiogenic and antitumor activities. Pegylated anti-GFR antibody fragment binds to and inhibits VEGFR-2, which may inhibit angiogenesis and tumor cell proliferation. Multivalent Fab' antibody fragments may exhibit improved retention and internalization properties compared to their parent IgGs.
A transdermal formulation containing the synthetic form of estradiol, the most potent, endogenously produced estrogen. Upon topical administration, estradiol diffuses through the cell membrane and binds to and activates specific intracellular estrogen receptors located on estrogen-responsive tissues, including the reproductive tract, breast, pituitary, hypothalamus, liver, and bone. The activated ligand-receptor complex binds to estrogen response elements on DNA and promotes the transcription of genes involved in the functioning of the female reproductive system and secondary sex characteristics. In addition, estradiol inhibits the pituitary secretion of the gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH) through a negative feedback mechanism.
A synthetic peptide vaccine consisting of the amino acids 126 through 134 of the human Wilms' Tumor protein-1 (WT1) with potential antitumor activity. WT1, a tumor associated antigen, is overexpressed in most types of leukemia and in a variety of solid cancers. Vaccination with WT1 126-134 peptide vaccine may induce a WT1-specific cytotoxic T-lymphocyte (CTL) response against WT1 expressing cells, resulting in cell lysis and inhibition of cancer cell proliferation.
A novel cancer vaccine designed to treat HER-2- and/or CEA-expressing cancers.
A proprietary, allogeneic tumor cell vaccine expressing a recombinant secretory form of the heat shock protein gp96 fusion (gp96-Ig) with potential antineoplastic activity. Upon administration of viagenpumatucel-L, the irradiated live tumor cells continuously secrete gp96-Ig along with its chaperoned tumor associated antigens (TAAs) into the blood stream, thereby activating antigen presenting cells, natural killer cells and priming potent cytotoxic T lymphocytes (CTLs) to respond against TAAs on the endogenous tumor cells. Furthermore, this vaccine may induce long-lived memory T cells that could fight recurring cancer cells. gp96-Ig is constructed by replacing the KDEL retention sequence of gp96, normally an endoplasmatic reticulum-resident chaperone peptide, with the Fc portion of mouse and human IgG1.
An orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. Auora kinase inhibitor MLN8054 binds to and inhibits Aurora kinase A, resulting in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation. Aurora A localizes in mitosis to the spindle poles and to spindle microtubules and is thought to regulate spindle assembly. Aberrant expression of Aurora kinases occurs in a wide variety of cancers, including colon and breast cancers.
A cancer vaccine comprised of multiple synthetic breast cancer peptides and the adjuvant tetanus toxoid helper peptide emulsified in the adjuvant Montanide ISA-51 with immunopotentiation activity. Vaccination with this cancer vaccine may elicit a specific cytotoxic T-lymphocyte response against breast cancer cells. Synthetic breast cancer peptides may stimulate the immune response against cells that produce breast cancer markers such as erbB2 (HER2/neu) while tetanus toxoid helper peptide binds to class II MHC molecules as a nonspecific vaccine helper epitope, resulting in a long-term immunopotentiation by increasing the helper T-cell response. Montanide ISA-51, also known as incomplete Freund's adjuvant or IFA, is a stabilized water-in-oil emulsion adjuvant containing mineral oil with mannide oleate added as a surfactant that non-specifically stimulates cell-mediated immune responses to antigens.
A cancer vaccine consisting of autologous dendritic cells transfected with autologous tumor mRNA and the human CD40 ligand (CD40L) gene with immunostimulatory and antitumor activities. Vaccination with autologous dendritic cell-autologous tumor mRNA-human CD40L vaccine may elicit a cytotoxic T cell response against tumor cells from which the autologous tumor mRNA was derived. When expressed by dendritic cells, tumor antigens and the co-stimulatory molecule CD40L, which binds to CD40 receptors on antigen presenting cells (APC), facilitate both humoral and cellular immune responses against tumor cells.
A cancer vaccine comprised of irradiated allogeneic pancreatic cancer cells transfected to express murine alpha-1,3-galactosyltransferase with potential antitumor activity. Vaccination is associated with the expression of murine alpha-1,3-galactosyl (alpha-gal) carbohydrate residues on cell membrane glycoproteins and glycolipids of the vaccine pancreatic cancer cell allograft; murine alpha-gal epitopes, not present on human cells, then induce a hyperacute rejection of the vaccine pancreatic cancer cell allograft. The hyperacute rejection involves the binding of pre-existing human anti-alpha-gal antibodies (which naturally occur against gut flora) to murine alpha-gal epitopes, resulting in the rapid activation of antibody-dependent cell-mediated cytotoxicity (ADCC) towards allograft cells. The host immune system then attacks endogenous pancreatic cancer cells, resulting in ADCC towards endogenous pancreatic cancer cells.
A natural or synthetic peptide cancer vaccine consisting of amino acid residues 27 through 35 of the melanoma-associated antigen MART-1 with potential antineoplastic activity. Vaccination with MART-1:27-35 peptide may induce cytotoxic host immune responses against melanoma cells that express this peptide.
A small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated.
The mesylate salt of a centrally-acting neurokinin 1 (NK1) receptor antagonist with antidepressant and antiemetic activities. Casopitant competitively binds to and blocks the activity of the NK-receptor, thereby inhibiting NK1-receptor binding of the endogenous tachykinin neuropeptide substance P (SP), which may result in antiemetic effects. SP is found in neurons of vagal afferent fibers innervating the brain-stem nucleus tractus solitarii and the area postrema, which contains the chemoreceptor trigger zone (CTZ), and may be elevated in response to chemotherapy. The NK-receptor is a G-protein receptor coupled to the inositol phosphate signal-transduction pathway and is found in both the nucleus tractus solitarii and the area postrema.
A non-infectious recombinant, quadrivalent vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid (L1) protein of human papillomavirus (HPV) types 6, 11, 16, and 18 with immunoprophylactic activity. L1 proteins are produced by separate fermentations in recombinant Saccharomyces cerevisiae, self-assembled into VLPs, and adsorbed onto amorphous aluminium hydroxyphosphate sulfate adjuvant following purification. The immunoprophylactic efficacy of L1 VLP vaccines, such as quadrivalent human papillomavirus (types 6,11,16,18) recombinant vaccine, appear to be mediated by the development of humoral immune responses. HPV Types 16 and 18 account for approximately 70% of cervical cancers and HPV Types 6 and 11 account for approximately 90% of genital warts.
A novel proapoptotic agent with potential antineoplastic activity. Survivin inhibitor YM155 selectively inhibits survivin expression in tumor cells, resulting in inhibition of survivin antiapoptotic activity (via theextrinsic or intrinsic apoptotic pathways) and tumor cell apoptosis. Survivin, a member of the inhibitor of apoptosis (IAP) gene family, is expressed during embryonal development and is absent in most normal, terminally differentiated tissues; upregulated in a variety of human cancers, its expression in tumors is associated with a more aggressive phenotype, shorter survival times, and a decreased response to chemotherapy. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=476771&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=476771&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61091"" NCI Thesaurus)
A multi-epitope Trojan antigen (TA) construct vaccine consisting of human melanoma antigen A3 (MAGE-A3) and human papillomavirus (HPV) 16 peptide epitopes linked by the furin-sensitive linker peptide RVKR (arginine-serine-lysine-arginine) with immunostimulatory and antitumor activities. The TA construct enters the cytoplasm of antigen-presenting cells (APC) and is processed by the endoplasmic reticulum (ER) and the trans-Golgi network (TGN), where the endopeptidase furin releases the epitopes from the RVKR linker peptide and, together with various exopeptidases, generates MHC class I-binding peptides. Expressed on the cell surfaces of APC, these MHC class I-binding peptides stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells that display the same peptide epitopes on their cell surfaces.
An orally active inhibitor of coagulation factor Xa with anticoagulant activity. Apixaban directly inhibits factor Xa, thereby interfering with the conversion of prothrombin to thrombin and preventing formation of cross-linked fibrin clots.
An orally bioavailable small molecule with potential antineoplastic activity. CHIR-265 binds and inhibits Raf kinases, which may result in a reduction of tumor cell growth and proliferation, and tumor cell death. In addition, this agent inhibits vascular endothelial growth factor receptor type 2 (VEGFR-2), thereby disrupting tumor angiogenesis. Raf kinases are critical enzymes in the Ras/Raf/MEK/ERK signaling pathway and are frequently upregulated in neoplasms.
A traditional Chinese herbal medicine derived from the plant Astragalus membranaceus with potential immunopotentiation activity. Jin Fu Kang may stimulate anti-tumor macrophage and natural killer cell activity and may enhance immune recognition of tumor cells by inhibiting the production of T-helper cell type 2 (Th2) cytokines such as interleukin-4 (IL-4) and interleukin-10 (IL-10).
A gel formulation containing reduced glutathione, L-cysteine, and anthocyanins with potential antioxidant, immunostimulating, and chemoprotective properties. Reduced glutathione is the primary cellular antioxidant and plays important roles in the antioxidation of reactive oxygen species and free radicals and, as a thiol-containing co-enzyme, in the detoxification of xenobiotic compounds. In addition, glutathione affects DNA synthesis and repair and exerts immunostimulating activity by increasing the production of interleukin-2 (IL-2), promoting antigen presentation, and stimulating T-suppressor/cytotoxic (CD8 cells) cells. The flavonoid anthocyanins, derived from various blue and purple flowering plants, are potent scavengers of reactive oxygen species.
A peptide vaccine consisting of the bcr-abl b3a2 fusion oncoprotein, frequently expressed in chronic myelogenous leukemia (CML), with potential antineoplastic activity. Vaccination with the bcr-abl (b3a2)-derived peptide vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells that express the bcr-abl b3a2 fusion protein. Fusion genes in CML typically result from the fusion of either BCR exon b2 or BCR exon b3 to ABL exon a2, a 'b3a2' or a 'b2a2' fusion.
A peptide vaccine consisting of the bcr-abl b2a2 fusion oncoprotein, frequently expressed in chronic myelogenous leukemia (CML), with potential antineoplastic activity. Vaccination with the bcr-abl (b2a2)-derived peptide vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells that express the bcr-abl b2a2 fusion protein. Fusion genes in CML typically result from the fusion of either BCR exon b2 or BCR exon b3 to ABL exon a2, a 'b3a2' or a 'b2a2' fusion.
The malate salt of amonafide, an imide derivative of naphthalic acid, with potential antineoplastic activity. Amonafide intercalates into DNA and inhibits topoisomerase II, resulting in DNA double-strand breaks (DSB) and inhibition of DNA replication and RNA synthesis.
The levo-enantiomer of an orally bioavailable polyphenolic aldehyde, derived primarily from unrefined cottonseed oil, with potential antineoplastic activity. Mimicking the inhibitory BH3 (Bcl-2 homology 3) domain of endogenous antagonists of Bcl-2, L-gossypol binds to and inhibits various anti-apoptotic Bcl-2 proteins, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. This agent has greater affinity for Bcl-2 proteins than racemic gossypol.
A synthetic antisense oligonucleotide against Bcl-2 messenger RNA with potential antitumor activity. Oligonucleotide SPC2996 binds to and inactivates Bcl-2 mRNA, thereby inhibiting the expression of Bcl-2 protein, promoting tumor cell apoptosis, and potentially enhancing the efficacy of standard cytotoxic chemotherapy. Linked to tumor drug resistance, the antiapoptotic protein Bcl-2 is upregulated in several types of cancers.
A vaccine consisting of two plasmids encoding the human cytomegalovirus (CMV) tegument phosphoprotein 65 (pp65), a major internal matrix protein, and glycoprotein B (gB), an important CMV component responsible for attachment and entry into cells, with immunostimulatory properties. Vaccination with VCL-CB01 may stimulate the host immune system to mount cellular and humoral immune responses against CMV positive cells, resulting in cell lysis.
A selective, orally available, 1,5-benzodiazepine-derivative gastrin/cholecystokinin 2 (CCK-2) receptor antagonist with potential antineoplastic activity. Z-360 binds to the gastrin/CCK-2 receptor, thereby preventing receptor activation by gastrin, a peptide hormone frequently associated with the proliferation of gastrointestinal and pancreatic tumor cells.
The lactate salt of tozasertib, a synthetic, small-molecule Aurora kinase inhibitor with potential antitumor activity. Tozasertib binds to and inhibits Aurora kinases (AKs), thereby inducing apoptosis in tumor cells in which AKs are overexpressed. AKs, a family of serine-threonine kinases, are essential for mitotic progression, spindle formation, centrosome maturation, chromosomal segregation, and cytokinesis.
A vaccine containing a heat-killed recombinant Saccharomyces cerevisiae yeast transfected with mutated forms of Ras, an oncogene frequently found in solid tumors, with potential immunostimulant and antitumor activity. Upon administration, GI-4000 vaccine elicits an immune response by stimulating a specific cytotoxic T-cell response against the mutated forms of Ras. This may lead to a destruction of cancer cells expressing a Ras mutation.
A replication-defective, recombinant oncolytic adenovirus encoding human endostatin with potential antineoplastic activity. Endostatin, a 20 kDa C-terminal proteolytic fragment of collagen XVIII, is an important angiogenesis inhibitor. Upon intratumoral administration, the adenovirus infects and replicates in tumor cells. The expressed endostatin may inhibit endothelial cell proliferation and angiogenesis which may result in a reduction of tumor growth.
A vaccine consisting of the melanocyte differentiation antigen Melan A (also called MART-1) encapsulated in noninfectious virus-like particles (VLP) with potential immunostimulating and antineoplastic activities. Upon administration, Melan-A VLP vaccine may activate the immune system to exert a specific cytotoxic T lymphocyte (CTL) response against cancer cells expressing the Melan A antigen, resulting in tumor cell lysis. Melan A is an antigen that is upregulated in most melanomas. VLP stimulates the immune system and promotes the CTL response.
A recombinant immunotoxin consisting of the anti-CD25 monoclonal antibody RFT5 fused to the deglycosylated ricin A-chain (dgA) with potential antitumor activity. The monoclonal antibody moiety of RFT5-dgA immunotoxin attaches to CD25 (the alpha chain of the IL-2 receptor complex) on the cell membrane; after internalization, the dgA moiety cleaves the N-glycosidic bond between the ribose and adenine base at position 4324 in 28S ribosomal RNA, resulting in ribosome inactivation, inhibition of protein synthesis, and cell death. CD25 is expressed on activated normal T and B cells and macrophages and is frequently upregulated in many hematologic malignancies.
An oral formulation of the phosphate salt of fludarabine, a synthetic purine nucleoside analogue antimetabolite with antineoplastic activity. Fudarabine is preferentially transported into malignant cells and metabolized by deoxycytidine kinase to its active form, 2-fluoro-ara-ATP; 2-fluoro-ara-ATP competes directly with deoxyadenosine triphosphate (dATP) and inhibits alpha DNA polymerase, RNA reductase, and DNA primase, which may result in inhibition of DNA synthesis and cell death.
A probiotic containing live, cultivated, freeze-dried lactic acid bacteria with gastrointestinal (GI) protective, anti-inflammatory, immunomodulating and potential antitumor properties. Oral administration of probiotic bacteria help maintain adequate colonization of the GI tract and modulate the composition of the normal microflora. Upon colonization of the GI tract, the probiotic bacteria form a protective barrier, interfere with the attachment of pathogenic bacteria and other harmful substances and may bind to and degrade carcinogens. This may prevent inflammation and possibly cancer. In addition, these bacteria produce lactic acid, thereby creating an acidic environment that is unfavorable for pathogens.
An orally-active, tyrosine kinase receptor inhibitor with potential antitumor activity. SU014813 binds to and inhibits the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR) alpha and beta, c-Kit and Fms-related tyrosine kinase 3 (Flt-3). This leads to an inhibition of cellular proliferation and angiogenesis and an induction of apoptosis.
A long-acting aqueous gel preparation of lanreotide, a synthetic cyclic octapeptide analogue of somatostatin. Lanreotide inhibits the secretion of growth hormone (GH) by binding to pituitary somatostatin receptors, and may inhibit the release of various other hormones, including thyroid stimulating hormone (TSH) and the gastroenteropancreatic hormones insulin, glucagon and gastrin. This agent also decreases circulating total and free insulin-like growth factor 1 (IGF-I). Lanreotide exhibits a high binding affinity for somatostatin receptor 2 (SSTR-2) and a lesser binding affinity for SSTR-5. However, compared to octreotide, this agent is less potent in inhibiting the release of growth hormone from the pituitary gland.
A trifunctional bispecific monoclonal antibody with potential antineoplastic activity. Catumaxomab has two antigen-recognition sites: one for human CD3, a T cell surface antigen; and one for human epithelial cell adhesion molecule (EpCAM), a cell surface antigen expressed by a variety of epithelial tumor cells. In addition, the modified Fc portion of this antibody binds Fc receptors on antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs). Catumaxomab brings T cells, EpCAM-expressing epithelial tumor cells and APCs together into tricellular complexes, which may result in a potent cytotoxic T-lymphocyte (CTL) response against EpCAM-expressing epithelial tumor cells. Fc-mediated binding of APCs in the tricellular complex potentiates EpCAM antigen presentation to T cells and the activation of anti-tumor cytotoxic T cell functions.
An orally bioavailable taxane compound, a C-4 methyl carbonate analogue of paclitaxel, labeled with radioactive carbon 14, with potential antineoplastic and radioimaging activities. BMS-275183 binds to tubulin and as a result inhibits microtubule disassembly or assembly. This leads to cell cycle arrest at the G2/M phase, thereby resulting in an inhibition of cell division and ultimately cell death. BMS-275183 may be useful for treating multi-drug resistant tumors as it does not appear to be a substrate for P-glycoprotein.
A recombinant chimeric, mouse-human monoclonal antibody IgG1, directed against the epidermal growth factor receptor (EGFR) and labeled with the radioisotope indium-111, with potential radioimaging activity. Indium 111 chimeric monoclonal antibody 806 binds to a specific epitope on EGFR-expressing tumor cells, allowing imaging of EGFR-expressing tumor cells using gamma scintigraphy. EGFR is a receptor tyrosine kinase that is involved in the regulation of cell growth and is found to be overexpressed on the cell surfaces of many tumor cell types.
A mixture of non-digestible carbohydrates, containing the fermentable plant fructans oligosaccharide and inulin, with potential prebiotic activity. Resisting hydrolysis by intestinal digestive enzymes, inulin and oligofructose serve as growth media and energy substrates for bifidobacteria in the colon; beneficial colonic commensal bacteria such as bifidobacteria may inhibit the colonization of the intestine by pathogenic bacteria and have been implicated to inhibit colon carcinogenesis. Oligofructose-enriched inulin may be administered in combination with probiotic bifidobacteria. In addition, this agent may promote the absorption of calcium and magnesium from the gastrointestinal tract.
An orally bioavailable liquid formulation containing the small molecule 2-methoxyestradiol with potential antineoplastic activity. 2-Methoxyestradiol, a naturally occurring estradiol metabolite, exerts its antitumor effect by inhibiting endothelial cells as well as tumor cells through multiple mechanisms. This agent binds to tubulin and disrupts microtubule formation, thereby preventing mitosis and subsequent cellular proliferation. In addition, 2-methoxyestradiol induces caspase activation, resulting in cell cycle arrest in G2 phase and apoptosis in due course. This agent also down-regulates hypoxia inducible factor-one alpha (HIF-1a). The nanocrystal colloidal dispersion increases the absorption of 2-methoxyestradiol, thereby improving its bioavailability, which results in enhanced drug plasma levels.
A replication-defective oncolytic adenovirus, encoding rat Her-2/neu (ErbB-2), with potential antineoplastic activity. Upon administration, adenovirus encoding rat HER-2/neu may induce an immune response against tumor cells expressing the HER-2/neu antigen, which may result in the immune-mediated inhibition of tumor cell proliferation and tumor cell death. Her-2/neu, a tumor-associated antigen and member of the epidermal growth factor receptor (EGFR) family of tyrosine kinases, is overexpressed in various tumor cell types.
A naturally-occurring human IgM monoclonal antibody with potential antineoplastic activity. Human monoclonal antibody 216, derived from the gene VH4-34, binds to the glycosylated epitope CDIM on the surface of both malignant and normal B cells. Upon binding to B cells, this antibody may crosslink two or more CDIM molecules, resulting in the formation of cell membrane pores, the disruption of cell membrane integrity, and B cell lysis; this mechanism of antibody-mediated cell death is direct and does not involve mechanisms of complement-mediated cytotoxicity or antibody-dependent cell-mediated cytotoxicity (ADCC). CDIM is the glyco-moiety of a 75kD B-cell cell surface glycoprotein.
A small synthetic molecule with potential antitumor activity. PHA-739358 inhibits catalytic activity of Aurora kinases, a family of serine-threonine kinases that are important regulators of cellular proliferation and division, and are overexpressed in certain types of cancer. Through the inhibition of Aurora kinases, PHA-739358 may induce cell growth arrest and apoptosis in tumor cells in which Aurora kinases are overexpressed. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=489092&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=489092&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61587"" NCI Thesaurus)
A fully human agonistic monoclonal antibody targeting the CD137 receptor with potential immunostimulatory and antineoplastic activities. Anti-CD137 monoclonal antibody specifically binds to and activates CD137-expressing immune cells, stimulating an immune response, in particular a cytotoxic T cell response, against tumor cells. CD137 is a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family of receptors and is expressed by activated T- and B-lymphocytes and monocytes; its ligand has been found to play an important role in the regulation of immune responses.
A plasmid DNA encoding an immunogenic peptide derived from the cancer-testis antigen NY-ESO-1 with potential immunostimulating and antitumor activities. Upon administration, NY-ESO-1 plasmid DNA cancer vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the NY-ESO-1 antigen, resulting in tumor cell lysis. NY-ESO-1 is a tumor associated antigen (TAA) found in normal testes and expressed on the surfaces of various tumor cells, including melanoma, breast, bladder, prostate, lung, ovarian, and hepatocellular tumor cells.
A peptide vaccine, containing nanoparticles of cholesteryl hydrophobized pullulan (CHP) complexed with the tumor-associated antigen HER-2/neu (ErbB-2), with potential antineoplastic activity. Her-2/neu, a member of the epidermal growth factor receptor (EGFR) family of tyrosine kinases, is overexpressed in various tumors, including breast, ovarian, and gastric cancers. Vaccination with CHP-HER-2 peptide vaccine may stimulate the host immune system to mount a humoral as well as a cytotoxic T-cell response against tumor cells expressing the HER-2/neu antigen. This results in an inhibition of tumor cell proliferation and tumor cell death. The self-aggregating CHP, composed of a pullulan backbone and cholesterol branches, forms stable colloidal nanoparticles in water.
A conjugate consisting of fluorescein isothiocyanate (FITC) conjugated with folate with potential antineoplastic activity. Folate-FITC binds to folate receptors, which are overexpressed on the surfaces of many cancer cells including kidney and ovarian cancer cells. Once bound to the cancer cell through the folate moiety of the conjugate, circulating anti-fluorescein antibodies may recognize and bind to the FITC moiety, resulting in antibody-dependent cellular cytotoxicity.
A radiolabeled antibody-targeted antineoplastic antibiotic consisting of the enediyne antibiotic calicheamicin conjugated with anti-Lewis Y antibody and labeled with indium In 111. In 111 CMD-193 binds to Lewis Y antigen-expressing tumor cells via its antibody moiety and is internalized; subsequently, the calicheamicin moiety binds to the minor groove of tumor cell DNA, causing double-strand DNA breaks, the inhibition of DNA synthesis, and apoptosis. The indium In 111 radiolabel allows the detection of CMD-193 distribution and tumor localization using gamma scintigraphy.
A pyrrolotriazine-based compound and a pan inhibitor of receptor tyrosine kinases with potential antineoplastic activity. Pan HER/VEGFR2 receptor tyrosine kinase inhibitor BMS-690514 binds to human epidermal growth factor receptors (EGFR) 1, 2 and 4 (HER1, HER2 and HER4) and vascular endothelial growth factor receptor 1, 2 and 3 (VEGFR-1, -2 and -3), all of which are frequently overexpressed by a variety of tumor types. Binding of this agent to these receptors may result in the inhibition of tumor cell proliferation; the inhibition of endothelial cell migration and proliferation and angiogenesis; and tumor cell death.
A specialized enteric nutritional supplement, containing substantial amounts of polyunsaturated fatty acids, arginine, and nucleotides, with potential immunostimulating activity. Compared to traditional enteric nutritional supplements, the omega-3 fatty acids/arginine/nucleotides oral supplement may enhance the growth, development, and activity of key components of the immune system, including lymphocytes, antigen presenting cells, and various cytokines.
An anthracycline derivative with potential antitumor activity. RTA 744 intercalates into DNA and interrupts topoisomerase II activity, thereby inhibits DNA replication and repair, as well as RNA and protein synthesis. Unlike other anthracycline derivatives, RTA 744 crosses the blood-brain barrier and reaches therapeutic levels in the brain. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=491929&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=491929&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61568"" NCI Thesaurus)
An oral bioadherent gel containing polyvinylpyrrolidone (PVP) and sodium hyaluronate with muco-protective activity. Upon oral application, this gel adheres to the mucosal surface of the mouth and throat, forming a thin layer that acts as a barrier to protect exposed and sensitized nerve endings from the painful stimuli associated with eating, drinking, and talking.
An orally active thrombopoietin receptor agonist with megakaryopoiesis stimulating activity. Eltrombopag binds to and stimulates the platelet thrombopoietin receptor (TPO-R or CD110), a member of the hematopoietin receptor superfamily. Activation of TPO-R leads to the proliferation and differentiation of megakaryocytes, thereby increasing the production of blood platelets.
A non-toxic, small-molecule, hypoxia-activated, 3,5-dinitrobenzamide nitrogen mustard pre-prodrug with potential antitumor activity. Upon intravenous administration, PR-104 is converted by systemic phosphatases to the alcohol intermediate PR-104A, which is reduced to form the active DNA-crosslinking mustard species hydroxylamine PR-104H intracellularly under hypoxic conditions. PR-104H specifically crosslinks hypoxic tumor cell DNA, resulting in the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis in susceptible hypoxic tumor cell populations while sparing normoxic tissues.
A simian virus 40 (SV40)-based shuttle vector, encoding small interfering RNA (siRNA), with potential antineoplastic activity. The expression of siRNA in target tumor cells transfected with an siRNA-expressing SV40 vector may result in siRNA-mediated silencing of target oncogenes and, so, the inhibition of tumor cell growth and the induction of tumor cell death.
An immunotoxin of a humanized monoclonal antibody C242 (MoAb HuC242) conjugated to a derivative of the cytotoxic agent maytansine, DM4, with potential antitumor activity. Cantuzumab ravtansine is generated from MoAb C242, which is raised against a cell surface superantigen, CA242, found in a variety of human tumor cells. Upon binding and entry, the immunoconjugate releases the maytansinoid agent DM4, which binds to tubulin, thereby affecting microtubule assembly/disassembly dynamics. As a result, this agent prevents cell division and reduces cell growth of cancer cells that express CA242.
A peptide vaccine consisting of the amino acids 280 through 288 of the melanoma antigen glycoprotein 100 (gp100) with potential antineoplastic activity. gp100:280-288(288V) peptide has a valine substitution at amino acid position 288 to improve immunogenicity. Vaccination with gp100:280-288(288V) peptide may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the gp100 antigen, resulting in decreased tumor growth.
A nanoparticle delivery system for recombinant human tumor necrosis factor (TNF) consisting of recombinant TNF bound to pegylated colloidal gold nanoparticles with potential antineoplastic activity. Upon intravenous administration, colloidal gold-bound recombinant human TNF travels through the bloodstream, avoiding immune detection and uptake by the reticuloendothelial system because of nanoparticle pegylation. Due to their size, the colloidal gold nanoparticles exit the circulatory system only at hyperpermeable tumor neovasculature sites; TNF then binds to and activates tumor cell TNF receptors, which may result in an increase in tumor cell apoptosis and a reduction in tumor cell proliferation. Compared to the administration of unbound TNF, colloidal gold-bound TNF may improve the efficacy and safety of TNF administration by delivering TNF specifically to tumor tissue.
Any skin disorder occurring as a consequence of injury to the skin tissue.
A controlled-release formulation of a biodegradable poly(ortho ester) polymer, encapsulating the indazole derivative granisetron, with antiemetic activity. Upon administration of APF530, the polymer slowly erodes and releases the active ingredient granisetron. As a selective serotonin receptor antagonist, granisetron competitively blocks the action of serotonin at 5-hydroxytryptamine3 (5-HT3) receptors, resulting in the suppression of nausea and vomiting over a sustained period of time.
A stabilized formulation of disodium glutathione disulfide (GSSG; oxidized glutathione) and cisplatin (1000:1) with potential chemoprotective and immunomodulating activities. Mimicking endogenous GSSG, glutathione disulfide NOV-002 acts as a competitive substrate for gamma-glutamyl-transpeptidase (GGT), which may result in the S-glutathionylation of proteins, predominantly actin, a redox stress on endoplasmic reticulum (ER), and ER stress-induced apoptosis; S-glutathionylation may be stimulated by reactive oxygen species (ROS) liberated by a glutathione disulfide NOV-002-induced increase in GGT activity. Glutathione disulfide NOV-002 may also induce phosphorylation of proteins such as ERK and p38, two kinases that play critical regulatory roles in cell proliferation and apoptosis. The cisplatin component of this agent does not provide an effective therapeutic concentration of cisplatin in vivo.
A poly(ADP-ribose) polymerase (PARP) -1 and -2 inhibitor with chemosensitizing and antitumor activities. With no antiproliferative effects as a single agent at therapeutic concentrations, ABT-888 inhibits PARPs, thereby inhibiting DNA repair and potentiating the cytotoxicity of DNA-damaging agents. PARP nuclear enzymes are activated by DNA single or double strand breaks, resulting in the poly(ADP-ribosyl)ation of other nuclear DNA binding proteins involved in DNA repair; poly(ADP-ribosyl)ation contributes to efficient DNA repair and to survival of proliferating cells exposed to mild genotoxic stresses as induced by as oxidants, alkylating agents or ionizing radiation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=496464&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=496464&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C60768"" NCI Thesaurus)
An orally available inhibitor of FMS-related tyrosine kinase 3 (FLT3, STK1, or FLK2), the tyrosine kinase ABL, and aurora kinases, with potential antineoplastic activity. Upon administration, FLT3/ABL/Aurora kinase inhibitor KW-2449 specifically binds to and inhibits both wild-type and mutated forms of FLT3, ABL and aurora kinases, which both interferes with the activation of signal transduction pathways mediated by these kinases and reduces the proliferation of susceptible cancer cells. FLT3 and ABL kinases are upregulated in certain tumor cells and play important roles in tumor cell proliferation and metastasis. Aurora kinases, serine-threonine kinases overexpressed by a wide variety of cancer cell types, play essential roles in mitotic checkpoint control.
A c-Myc antisense phosphorodiamidate morpholino oligomer (PMO) with potential antineoplastic activity. Phosphorodiamidate morpholino oligomer AVI-4126 binds to c-Myc mRNA and blocks its translation, which may result in the death of tumor cells overexpressing c-Myc. Differing from traditional antisense oligodeoxynucleotides (ODNs), neutrally charged PMOs are composed of subunits of nucleic acid bases linked to a synthetic backbone and, so, are less prone to enzymatic degradation. c-Myc, a proto-oncogene overexpressed in a variety of cancers, is involved in cellular proliferation, differentiation, and apoptosis.
An orally active inhibitor of heat shock protein 90 (HSP90) with potential antineoplastic activity. HSP90, a chaperon protein upregulated in a variety of tumor cells, regulates the folding and degradation of many oncogenic signaling proteins. HSP90 inhibitor BIIB021 specifically blocks active HSP90, thereby inhibiting its chaperon function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. As a result, CNF2024 has the potential to inhibit the growth of a wide range of cancer cells in both solid tumors and blood-based cancers.
The liposomal preparation of oxaliplatin, an organoplatinum complex in which the platinum atom is complexed with 1,2-diaminocyclohexane (DACH) and with an oxalate ligand as a 'leaving group'. A leaving group is an atom or a group of atoms that is displaced as a stable species taking with it its bonding electrons. After displacement of the labile oxalate ligand leaving group, the active oxaliplatin derivatives (monoaquo and diaquo DACH platinum) alkylate macromolecules, and form both inter- and intra-strand platinum-DNA crosslinks, thereby inhibiting DNA replication and resulting in cytotoxicity. The DACH side chain appears to inhibit DNA repair mechanism, therefore overcoming the limits observed in other platinum-based therapies.
Spores of the bacterial strain Clostridium novyi-NT, the attenuated obligate anaerobic C. novyi, with potential immunostimulating, bacteriolytic, and antineoplastic activities. Upon intravenous administration, Clostridium novyi-NT spores germinate exclusively in hypoxic tissue, such as avascular regions of tumors. Germination results in lysis and destruction of surrounding viable tumor cells. Due to their anaerobic nature, C. novyi-NT spores do not proliferate in oxygenated tumor regions. However, this agent may stimulate the immune system to exert a cellular immune response, resulting in additional killing of tumor cells not lysed by the bacteria, including those in the well-oxygenated tumor area.
The mesylate salt of obatoclax, a synthetic small-molecule inhibitor of the bcl-2 family of proteins with potential pro-apoptotic and antineoplastic activities. Obatoclax binds to members of the Bcl-2 protein family, preventing the binding of these anti-apoptotic proteins to the pro-apoptotic proteins Bax and Bak and so promoting the activation of the apoptotic pathway in Bcl-2-overexpressing cells. The Bcl-2 family of proteins (bcl-2, bcl-xl, bcl-w, and Mcl-1) are overexpressed in a wide variety of cancers, including those of the lymphatic system, breast, lung, prostate, and colon.
A peptide vaccine containing amino acids residues from 340 through 349 of the latent membrane protein-2 (LMP-2) of the Epstein-Barr virus (EBV) with potential immunostimulating and antineoplastic activities. LMP-2, an EBV transmembrane protein, is expressed in various malignancies including nasopharyngeal cancer and EBV-positive Hodgkin disease. Vaccination with the LMP-2:340-349 peptide may boost the immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against LMP-2 producing cells, resulting in cell lysis and inhibition of cancer cell proliferation.
A peptide vaccine containing amino acids residues from 419 through 427 of the latent membrane protein-2 (LMP-2) of the Epstein-Barr virus (EBV) with potential immunostimulating and antineoplastic activities. LMP-2, an EBV transmembrane protein, is expressed in various malignancies including nasopharyngeal cancer and EBV-positive Hodgkin disease. Vaccination with the LMP-2:49-427 peptide may boost the immune system to mount a specific cytotoxic T-lymphocyte response against LMP-2 producing cells, resulting in cell lysis and inhibition of cancer cell proliferation.
A preparation of allogeneic Epstein-Barr virus (EBV) specific cytotoxic T-lymphocytes (CTL) with potential antineoplastic activity. The allogeneic EBV-specific CTLs are either harvested from a donor with an EBV-positive tumor or are donor CTLs activated against EBV-specific antigens ex vivo. Administration into a patient exerts a CTL response against EBV-positive tumor cells or EBV-infected cells. This results in cell lysis and inhibition of cancer cell proliferation. EBV, a ubiquitous human herpes virus, is associated with various malignancies, including nasopharyngeal carcinoma, Hodgkin disease, non-Hodgkin lymphoma, and other lymphomas.
A synthetic cancer vaccine comprised of multiple peptides derived from MAGE-1A, Her-2/neu, and folate binding protein (FBP), with potential immunostimulating and antineoplastic properties. MAGE-A1, Her-2/neu, and FBP proteins are simultaneously over-expressed in various cancer cell types, such as epithelial ovarian cancer. The MAGE-A1, Her-2/neu, FBP peptides cancer vaccine includes the peptides MAGE-A1:161-169, FBP:191-199, Her-2/neu:369-377, MAGE-A1:96-104, and Her-2/neu:754-762. Vaccination with this cancer vaccine may activate the immune system to mount a cytotoxic T-cell (CTL) response against tumor cells expressing the corresponding antigens, resulting in tumor cell lysis.
A formulation of the semisynthetic vinca alkaloid, vinorelbine, encapsulated within liposomes, with antineoplastic activity. Vinorelbine binds to tubulin and prevents formation of the mitotic spindle, resulting in cell cycle arrest in metaphase. Like other vinca alkaloids, vinorelbine may also interfere with the metabolism of nucleic acids, lipids, amino acids, cAMP, and glutathione, as well as other biological processes including calmodulin-dependent Ca2+-transport, ATPase activity, or cellular respiration. Liposomal delivery of vinorelbine improves drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic effects while lowering the toxicity profile.
A combination preparation containing minocycline, a broad-spectrum, semi-synthetic tetracycline antibiotic, and ethylenediaminetetraacetate (EDTA) with antimicrobial and anticoagulant activities. Minocycline exerts its bacteriostatic effect by binding to the bacterial 30S ribosomal subunit and preventing binding of aminoacyl-tRNA to the mRNA-ribosome complex during protein translation. This leads to an inhibition of bacterial protein synthesis and consequently interferes with cell growth. EDTA, a metal chelator, exerts its anticoagulant activity by binding to calcium, thereby impeding the activity of calcium-dependent coagulation proteins. This leads to an inhibition of thrombotic occlusion and prevention of bacterial colonization that could occur upon clot formation.
A formulation of a plasmid DNA encoding an inactivated form of the carcinogen activator cytochrome P450 1B1 (CYP1B1) encapsulated in biodegradable poly-DL-lactide-coglycolide microparticles with potential antineoplastic activity. CYP1B1, an extrahepatic monooxygenase of the cytochrome P450 family, is overexpressed in many cancers with only restricted expression in normal tissues. Vaccination with ZYC300 may stimulate the immune system to elicit a cytotoxic T lymphocyte (CTL) response against the tumor associated antigen CYP1B1, thereby causing lysis of tumor cells expressing CYP1B1.
An orally bioavailable small molecule with potential antineoplastic activity. AT7519M selectively binds to and inhibits cyclin dependent kinases (CDKs), which may result in cell cycle arrest, induction of apoptosis, and inhibition of tumor cell proliferation. CDKs are serine/threonine kinases involved in regulation of the cell cycle and may be overexpressed in some types of cancer cells.
A mature polarized dendritic cell with potent immunostimulating activity. Treating dendritic cells (DCs) with interferon-alpha (IFN-a) and polyinosinic:polycytidylic acid (p-I:C) in addition to a cytokine cocktail (tumor necrosis factor alpha/Interleukin-1beta/IFN-gamma) produces mature but not exhausted alpha type-1 polarized DCs (alphaDC1) that are capable of: 1) high responsiveness to other lymphoid chemokines, and 2) producing high level of interleukin-12p70 (IL-12p70). Therefore, alphaDC1 has a much more significant capability of inducing helper T cell (CD4+ T-cell) responses in comparison with the ""gold standard"" DCs. When pulsed with specific tumor associated antigens (TAAs), alphaDC1 is able to induce a potent cytotoxic T lymphocyte (CTL) response against TAAs; as a result it can be used as a cancer vaccine.
A recombinant protein consisting of human interleukin 3 (IL3) fused to the first 388 amino acids of diphtheria toxin [DT(388)] (DT388IL3) with potential antineoplastic activity. Upon intravenous administration, the IL3 moiety of the DT(388)IL3 fusion protein SL-401 binds to IL3 receptors on cells expressing the receptor. Subsequently, the DT(388) toxin moiety, which contains both translocation and catalytic domains, is transported across the cell membrane via endocytosis. Within the cytosol, the catalytic domain of the toxin both catalyzes the ADP-ribosylation of, and inactivates, translation elongation factor 2 (EF-2), which results in the inhibition of translation during protein synthesis. IL3 may be overexpressed by a variety of cancers, including blastic plasmacytoid dendritic cell neoplasm and acute myeloid leukemia (AML).
A fully human IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR) with potential antineoplastic activity. EGFR is a cell surface receptor tyrosine kinase, overexpressed on many cancer cells. Zalutumumab selectively binds to and blocks binding of EGF and transforming growth factor-alpha (TGF-a) to the EGFR receptor, thereby interfering with cellular signaling, leading to cell growth inhibition and apoptosis in tumor cells. In addition, zalutumumab also triggers cell lysis mediated through antibody dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells.
An orally bioavailable benzimidazole targeting the platelet-derived growth factor receptor (PDGFR) subtypes alpha and beta and FMS-related tyrosine kinase 3 (Flt3), with potential antineoplastic activity. Upon oral administration, crenolanib binds to and inhibits both wild-type and mutated forms of PDGFR and Flt3, which may result in the inhibition of PDGFR- and Flt3-related signal transduction pathways. This results in inhibition of tumor angiogenesis and tumor cell proliferation in PDGFR and/or Flt3 overexpressing tumor cells. PDGFR and Flt3, class III receptor tyrosine kinases, are upregulated or mutated in many tumor cell types.
A peptide vaccine comprised of an epitope of human Wilms tumor 1 (WT-1) with potential antineoplastic activity. WT-1, a transcription factor, is overexpressed in most types of leukemia and in some solid cancers. Vaccination with the WT-1 analog peptide vaccine may induce a cytotoxic T-lymphocyte (CTL) response against WT-1 expressing cells, resulting in cell lysis and inhibition of cancer cell proliferation.
Human autologous peripheral blood lymphocytes (PBLs) transduced with a glycoprotein 100 (gp100) epitope-determined T cell receptor (TCR) gene, with potential antineoplastic activity. PBLs are isolated from a melanoma patient and pulsed with a viral vector encoding the TCR specific for amino acid residues 154-162 of gp100 (KTWGQYWQV). After expansion ex vivo, the transduced autologous PBLs, expressing this specific TCR, are reintroduced into the patient and bind to melanoma cells expressing the gp100 protein, which may result in specific cytotoxic T-lymphocyte (CTL) killing of gp100-expressing melanoma cells. gp100 is a melanocyte lineage-specific antigen overexpressed in melanomas.
An attenuated oncolytic Edmonston (Ed) strain of measles virus (MV) encoding the soluble extracellular N-terminal domain of human carcinoembryonic antigen (CEA) (MV-CEA) with potential antineoplastic activity. The cellular receptor of MV is human CD46 antigen, a type 1 integral membrane glycoprotein found on nearly all human tissues and overexpressed on many cancer cell types. Mediated through CD46, both haemagglutinin and fusion glycoproteins of MV are required for the attachment to and fusion of host cell membranes, thereby leading to syncytia and cell lysis. The expressed CEA, a tumor associated antigen, can be detected in serum and used as a sensitive marker to monitor viral gene expression in order to easily optimize individual therapy. Compared to wild-type MV, the Ed strain of MV has a lower affinity for the MV receptor signaling lymphocyte-activation molecule (CD150), mainly expressed in B- and T-lymphocytes, but a higher affinity for CD46.
An injectable formulation of the radioisotope yttrium Y 90 encapsulated in resin microspheres with potential antineoplastic activity. When injected into arterial vasculature supplying the tumor, yttrium Y 90 resin microspheres occlude tumor blood vessels and selectively deliver a cytotoxic dose of beta emitting yttrium Y 90 to the tumor site, which may result in tumor cell death and tumor regression.
A plasmid DNA encoding the A chain of the diphtheria toxin (DT-A) driven by the transcriptional regulatory sequences of human H19, with potential antineoplastic activity. Because the expression of DT-A is under the control of H19 promotor elements, DT-A is selectively expressed in tumor cells capable of turning on H-19. DT-A catalyzes ADP-ribosylation of translation elongation factor 2 (EF-2), resulting in the inhibition of protein synthesis and apoptosis. In addition, DT-A protein released from lysed cells cannot enter and kill neighboring cells because of the absence of the DT-B chain, further enhancing the selective cytotoxicity of this agent. Human H19 is a paternally-imprinted, oncofetal gene encoding an RNA product; it acts as a riboregulator in gene expression and is found at substantial levels in different human tumor cell types while its expression in normal adult tissue is limited.
A broad-acting, apoptosis-inducing, small molecule with potential antineoplastic activity. Although the exact mechanism of action has yet to be fully elucidated, apoptosis inducer MPC-2130 exhibits proapoptotic activities in tumor cells, including membrane phosphatidylserine externalization, release of cytochrome C from mitochondria, caspase activation, cell condensation, and DNA fragmentation. In addition, because this agent is not a substrate for several types of multidrug resistance (MDR) ABC superfamily transporters, such as P-glycoprotein 1 (MDR-1), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein 1 (BCRP1/ABCG2), it may be useful in treating MDR tumors that express these particular MDR efflux pumps.
A cell-based vaccine comprised of prostate cancer cells transduced with an adenoviral vector encoding human RTVP-1 (AdRTVP-1), with potential antineoplastic and immunostimulating activities. RTVP-1, also referred to as glioma pathogenesis-related protein 1 (GLIP1), is down-regulated in prostate tumors. Regulated by tumor suppressor p53, the expression of RTVP-1 functions as a tumor suppressor, and is abundant in normal human prostate epithelial cells as well as in differentiated macrophages. Administration of this vaccine leads to an induction of apoptosis through the expression of RTVP-1 and results in a reduction in cellular proliferation in prostate cancer cells. In addition, this cancer-cell based vaccine may induce a cytotoxic T lymphocyte (CTL) response against prostate specific tumor associated antigens, resulting in an immune-mediated prostate cancer cell death. Furthermore, RTVP-1 stimulates CTL and natural killer (NK) cell activities.
An orally bioavailable diaminopyrimidine compound and a cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. CDKs are ATP-dependent serine/threonine kinases that are important regulators of cell cycle progression and are frequently overexpressed in cancerous cells. R547 selectively binds to and inhibits CDKs, especially CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1. The inhibition of CDKs results in cell cycle arrest, inhibition of tumor cell proliferation, and induction of apoptosis. By inhibiting CDK activity, R547 also reduces phosphorylation of the retinoblastoma (Rb) protein, thereby preventing activation of transcription factor E2F and leading to further suppression of tumor cell proliferation.
A monoclonal antibody (MoAb) against extracellular melanin with tumor targeting activity. Anti-melanin monoclonal antibody PTI-6D2 binds to extracellular melanin, a melanocyte pigment which is released during tumor cell turnover from dead melanoma tumor cells, while avoiding the binding of melanin in normal, healthy tissue because of melanin's normal intracellular location. Upon labeling with the beta-emitting radioisotope rhenium Re 188 (PTI-188), this MoAb may target multiple melanoma (MM) cells, thereby delivering a cytotoxic dose of radiation specifically to the targeted tumor cells.
A chimeric IgG1 monoclonal antibody against CD123 (Interleukin-3 receptor alpha chain) with potential antineoplastic activity. Derived from mouse monoclonal antibody 7G3, anti-CD123 monoclonal antibody CSL360 binds to and neutralizes CD123 which is upregulated on leukemic stem cells (LSC) in acute myeloid leukemia (AML). This may inhibit IL-3-dependent signalling and proliferation and may prevent the uncontrolled growth and differentiation of mutated LSC.
A liposome-encapsulated peptide vaccine consists of a synthetic peptide derived from the mucin 1 (MUC-1) antigen with potential antineoplastic property. MUC-1 antigen is a high-molecular-weight transmembrane glycoprotein, which is overexpressed on many tumor cells. Upon vaccination, MUC-1 peptide vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against MUC-1 expression tumor cells, thereby results in inhibiting tumor growth. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=529341&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=529341&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C2195"" NCI Thesaurus)
A second-generation E2F1 pathway activator with potential antineoplastic activity. ARQ 171 induces the expression of E2F transcription factor 1, thereby activating the E2F1-mediated checkpoint process. E2F1, down-regulated in cancer cells, regulates expression of genes involved in the cell cycle progression from G1 into S phase. The G1/S checkpoint process selectively induces cell cycle arrest in cancer cells with irreparable DNA damages and triggers subsequent apoptosis, while allowing cell division to proceed in cells without or with minor reparable DNA damage. As a result, this agent exerts anti-tumor activity through checkpoint activation independent of p53 mediated tumor suppression.
A proprietary preparation of mycobacterial DNA oligonucleotides embedded in mycobacterial cell wall fragments derived from cultures of Mycobacterium phlei, with potential immunomodulatory and antineoplastic activities. DNA oligonucleotides in the mycobacterial cell wall-DNA complex (MCC) are capable of inducing apoptosis by increasing BAX protein levels, releasing cytochrome C from mitochondria, and activating caspase-3 and -7. This leads to the cleavage of poly (ADP-ribose) polymerase and the release of nuclear matrix proteins (NuMA). In addition to its pro-apoptotic effect, MCC activates monocytes and macrophages to produce various cytokines, including interleukin 6 (IL-6), IL-8, IL-12, IL-18, and tumor necrosis factor alpha (TNF-a). This leads to an activation of natural killer cells and cytotoxic T lymphocytes and to interferon gamma (INF-g) synthesis, thereby attaining an anti-angiogenic effect.
A water-soluble triazole prodrug with broad-spectrum antifungal activity. Isavuconazole is absorbed easily, given either orally or intravenously, and is hydrolyzed to its active moiety BAL4815 by plasma esterases. BAL4815 inhibits fungal cytochrome P450 lanosterol 14-alpha-demethylase (CYP51) that catalyzes the conversion of lanosterol to ergosterol, an important component of the fungal cell membrane. Enzyme inhibition by this agent leads to a decrease in ergosterol pool and therefore disturbs synthesis of fungal cell membrane, thereby increasing cell membrane permeability and promoting loss of essential intracellular elements. This ultimately causes fungal cell lysis and death.
An extract of fermented wheat germ containing a concentrated, standardized amount of methoxy-substituted benzoquinones with immunomodulatory and potential antineoplastic activities. Fermented wheat germ extract (FWGE) inhibits the activities of several enzymes involved in de novo nucleic acid synthesis and in supplying the dNTP pool required for DNA replication. This agent also induces caspase-3- mediated inactivation of poly(ADP)ribose polymerase (PARP), a key enzyme in DNA repair that is overexpressed in many cancers; cleavage of PARP prevents DNA repair and induces apoptosis. The benzoquinones may contribute to the immunomodulatory effects of FWGE, down-regulating major histocompatibility complex class I (MHC-1) protein on the surface of cancer cells, allowing natural killer (NK) cell surveillance; and up-regulating the expression of intracellular adhesion molecule 1 (ICAM-1) on tumor endothelial cells.
A fully human, high-affinity IgG1 monoclonal antibody directed against the B cell CD20 cell surface antigen with potential antineoplastic activity. Ofatumumab binds specifically to CD20 on the surfaces of B cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B cells overexpressing CD20. The CD20 antigen, found on over 90% of B cells, B cell lymphomas, and other B cells of lymphoid tumors of B cell origin, is a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel; it is exclusively expressed on B cells during most stages of B cell development.
Subependymal giant cell astrocytoma that occurs during childhood.
An allogeneic human cytotoxic T-lymphocyte cell line (TALL-104) with potential antineoplastic activity. TALL-104 is an IL-2-dependent human leukemic T cell line, expressing CD8 and T-cell receptor CD3, but not CD16. Because these cells are endowed with MHC-non-restricted killer activity, TALL-104 has destructive potential against a broad range of tumors, while sparing normal cells. Upon administration, TALL-104 targets and interacts with tumor cells and activates apoptotic and necrotic pathways, eventually leading to lysis of tumor cells. In addition, TALL-104 may induce secretion of various cytokines, such as interferon-gamma, thereby potentially enhancing the cytotoxic activity.
A murine IgG1 monoclonal anti-idiotype antibody, containing a variable antigen-binding region that functionally mimics the three-dimensional structure of a specific epitope on the ovarian cancer tumor-associated antigen CA-125, with potential antineoplastic activity. With a variable antigen-binding region that acts as a surrogate antigen for CA-125, abagovomab may stimulate the host immune system to elicit humoral and cellular immune responses against CA-125-positive tumor cells, resulting in inhibition of tumor cell proliferation.
A humanized monoclonal antibody directed against the human CS1 (CD2 subset 1, CRACC, SLAMF7) antigen with potential antineoplastic activity. Elotuzumab binds to the CS1 antigen, which may trigger antibody-dependent cellular cytotoxicity (ADCC) in cells expressing CS1. CS1 is a cell surface glycoprotein belonging to the CD2 subset of the immunoglobulin superfamily (IgSF) and is highly expressed by multiple myeloma cells, but minimally expressed by normal cells.
Any disorder of the liver occurring as a consequence of injury to the liver parenchyma.
Wilms tumor is a form of kidney cancer that primarily develops in children. Nearly all cases of Wilms tumor are diagnosed before the age of 10, with two-thirds being found before age 5.Wilms tumor is often first noticed because of abdominal swelling or a mass in the kidney that can be felt upon physical examination. Some affected children have abdominal pain, fever, a low number of red blood cells (anemia), blood in the urine (hematuria), or high blood pressure (hypertension). Additional signs of Wilms tumor can include loss of appetite, weight loss, nausea, vomiting, and tiredness (lethargy).Wilms tumor can develop in one or both kidneys. About 5 to 10 percent of affected individuals develop multiple tumors in one or both kidneys. Wilms tumor may spread from the kidneys to other parts of the body (metastasize). In rare cases, Wilms tumor does not involve the kidneys and occurs instead in the genital tract, bladder, abdomen, chest, or lower back. It is unclear how Wilms tumor develops in these tissues.With proper treatment, children with Wilms tumor have a 90 percent survival rate. However, the risk that the cancer will come back (recur) is between 15 and 50 percent, depending on traits of the original tumor. Tumors usually recur in the first 2 years following treatment and develop in the kidneys or other tissues, such as the lungs. Individuals who have had Wilms tumor may experience related health problems or late effects of their treatment in adulthood, such as decreased kidney function, heart disease, and development of additional cancers.
A rare primary bone dysplasia with characteristics of small, flat epiphyses (especially the capital femoral epiphyses), rhizomelic shortening of limbs, cleft of secondary palate, micrognathia, mild joint contractures and facial dysmorphism (including mildly upward-slanting palpebral fissures, hypertelorism, broad nasal tip). Additionally reported features include scoliosis, genu valgum, mild pectus excavatum, platyspondyly, dislocated radial heads, brachydactyly, hypoplastic fibulae and talipes equinovarus.
Facial contours, as viewed from the front, show a broad upper face/cranium and lower face/mandible, creating a square appearance.
An abnormality of the appearance of the face caused by constant contraction of the lips leading to a puckered or pursed appearance.
Reduction in density of metaphyseal bony tissue.
An abnormality of temperature homeostasis. [HPO:probinson]
Traboulsi syndrome is characterized by dislocated crystalline lenses and anterior segment abnormalities in association with a distinctive facies involving flat cheeks and a beaked nose. Some affected individuals develop highly unusual nontraumatic conjunctival cysts (filtering blebs), presumably caused by abnormal thinning of the sclera (Patel et al., 2014).
Mutations in the CRYBB2 gene have been found to cause several types of cataract, which have been described as congenital cerulean, 'blue dot,' Coppock-like, sutural with punctate and cerulean opacities, pulverulent embryonal, pulverulent with cortical opacities, dense posterior star-shaped subcapsular with pulverulent opacities in the cortical and embryonal regions, and dense embryonal. Before it was known that mutations in the CRYBB2 gene cause several types of cataract, the preferred title of this entry was 'Cataract, Congenital, Cerulean Type 2,' with the symbol CCA2.
Syndrome with characteristics of deafness, central hypoventilation, congenital ocular paralysis and developmental retardation. Cardiac anomalies and paralysis of the vocal chords may also be present. Six cases have been reported so far. Transmission is thought to be autosomal recessive.
Syndrome with characteristics of variable horizontal gaze dysfunction, profound and bilateral sensorineural deafness associated commonly with severe inner ear maldevelopment, cerebrovascular anomalies, cardiac malformation, developmental delay and occasionally autism. The syndrome is caused by homozygous mutations in the HOXA1 gene (7p15.2) and is transmitted in an autosomal recessive manner. The syndrome overlaps clinically and genetically with Athabaskan brain dysfunction syndrome, however unlike Athabaskan brain dysfunction syndrome it does not manifest central hypoventilation.
Axenfeld-Rieger syndrome is a disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, which results in blindness from glaucoma in approximately 50% of affected individuals. Systemic abnormalities, including cardiac and dental anomalies, are associated. For a general phenotypic description and a discussion of genetic heterogeneity and nomenclature of Axenfeld-Rieger syndrome, see RIEG1 (180500).
Agammaglobulinemia, non-Bruton type (autosomal agammaglobulinemia) is a rare form of agammaglobulinemia, a primary immunodeficiency disease, and is characterized by variable immune dysfunction with frequent and recurrent bacterial infections and/or chronic diarrhea.
Left ventricular noncompaction is a heart (cardiac) muscle disorder that occurs when the lower left chamber of the heart (left ventricle), which helps the heart pump blood, does not develop correctly. Instead of the muscle being smooth and firm, the cardiac muscle in the left ventricle is thick and appears spongy. The abnormal cardiac muscle is weak and has an impaired ability to pump blood because it either cannot completely contract or it cannot completely relax. For the heart to pump blood normally, cardiac muscle must contract and relax fully.Some individuals with left ventricular noncompaction experience no symptoms at all; others have heart problems that can include sudden cardiac death. Additional signs and symptoms include abnormal blood clots, irregular heart rhythm (arrhythmia), a sensation of fluttering or pounding in the chest (palpitations), extreme fatigue during exercise (exercise intolerance), shortness of breath (dyspnea), fainting (syncope), swelling of the legs (lymphedema), and trouble laying down flat. Some affected individuals have features of other heart defects. Left ventricular noncompaction can be diagnosed at any age, from birth to late adulthood. Approximately two-thirds of individuals with left ventricular noncompaction develop heart failure.
GARS-associated axonal neuropathy (Charcot-Marie-Tooth neuropathy type 2D / distal spinal muscular atrophy V [CMT2D/dSMA-V]) is characterized by adolescent or early-adult onset of weakness in the hands that may be preceded by transient cramping and pain in the hands on exposure to cold and cramping in calf muscles on exertion. This is followed by progressive weakness and atrophy of thenar and first dorsal interosseus muscles; hypothenar eminence is spared until later in the course of illness. The lower limbs are involved in about half of affected individuals, with severity varying from weakness and atrophy of the extensor digitorum brevis and weakness of toe dorsiflexors to classic peroneal muscular atrophy with foot drop. The phenotype is considered the CMT2D subtype when sensory deficits (reduction of pinprick, temperature, touch, and vibration perception in a stocking and [less often] glove pattern) are present and dSMA-V when sensory deficits are absent.
Hereditary congenital facial paresis (HCFP) is the isolated dysfunction of the facial nerve (CN VII). HCFP is considered to be distinct from Moebius syndrome (157900), which shares some of the same clinical features. Genetic Heterogeneity of Hereditary Congenital Facial Paresis One locus for HCFP (HCFP1) has been mapped to chromosome 3q. Another locus (HCFP2; 604185) has been mapped to chromosome 10q. HCFP3 (614744) is caused by mutation in the HOXB1 gene (142968) on chromosome 17q21.
Severe combined immunodeficiency refers to a genetically and clinically heterogeneous group of disorders with defective cellular and humoral immune function. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms, including Candida albicans, Pneumocystis carinii, and cytomegalovirus, among many others. Laboratory analysis shows profound lymphopenia with diminished or absent immunoglobulins. The common characteristic of all types of SCID is absence of T cell-mediated cellular immunity due to a defect in T-cell development. Without treatment, patients usually die within the first year of life. The overall prevalence of all types of SCID is approximately 1 in 75,000 births (Fischer et al., 1997; Buckley, 2004). SCID can be divided into 2 main classes: those with B lymphocytes (B+ SCID) and those without (B- SCID). Presence or absence of NK cells is variable within these groups. The most common form of SCID is X-linked T-, B+, NK- SCID (300400) caused by mutation in the IL2RG gene (308380) on chromosome Xq13.1. Autosomal recessive SCID includes T-, B+, NK- SCID (600802) caused by mutation in the JAK3 gene (600173) on 19p13.1; T-, B+, NK+ SCID (608971) caused by mutation in the IL7R gene (146661) on 5p13, the CD45 gene (151460) on 1q31-q32, or the CD3D gene (186790) on 11q23; T-, B-, NK- SCID (102700) caused by mutation in the ADA (608958) gene on 20q13.11; T-, B-, NK+ SCID with sensitivity to ionizing radiation caused by mutation in the Artemis gene on 10p; and T-, B-, NK+ SCID caused by mutation in the RAG1 and RAG2 genes on 11p13 (Kalman et al., 2004). Approximately 20 to 30% of all SCID patients are T-, B-, NK+, and approximately half of these patients have mutations in the RAG1 or RAG2 genes (Schwarz et al., 1996; Fischer et al., 1997).
Insufficient weight gain or inappropriate weight loss for a child, that is attributed to an endogenous recurrent infections.
Increased susceptibility to opportunistic infections, as manifested by recurrent episodes of infection by opportunistic agents, i.e., by microorganisms that do not usually cause disease in a healthy host, but are able to infect a host with a compromised immune system.
Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal recessive disorder of the peripheral nervous system characterized by early-onset distal muscle weakness and atrophy, foot deformities, and sensory loss affecting all modalities. Affected individuals develop deafness by the third decade of life (summary by Okamoto et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive Charcot-Marie-Tooth disease, see CMT4A (214400).
A reduction in the number of axons in the peripheral nervous system.
Curvilinear intracellular accumulation of autofluorescent lipopigment storage material within axons.
Hair whose growth is slower than normal.
The OAFNS phenotype combines abnormalities of the morphogenesis of the first and second branchial arches (microtia/skin tags, epibulbar dermoids, cleft lip/palate, mandibular hypoplasia, and facial asymmetry) with malformations due to the anomalous development of the frontonasal eminence and maxillary processes (notched/bifid nasal tip, cleft lip and/or palate, and encephalocele) (Gabbett et al., 2008).
A hearing loss condition that appears as a consequence of annular ligament destruction followed by excessive connective tissue production during the healing process. This condition is mainly observed in otosclerosis, but is also found in chronic otitis media with tympanosclerosis, and other rare bone diseases such as Paget's disease and osteogenesis imperfecta (Lobstein disease).
Myofibrillar myopathy is characterized by slowly progressive weakness that can involve both proximal and distal muscles. Distal muscle weakness is present in about 80% of individuals and is more pronounced than proximal weakness in about 25%. A minority of individuals experience sensory symptoms, muscle stiffness, aching, or cramps. Peripheral neuropathy is present in about 20% of affected individuals. Overt cardiomyopathy is present in 15%-30%.
6q24-related transient neonatal diabetes mellitus (6q24-TNDM) is defined as transient neonatal diabetes mellitus caused by genetic aberrations of the imprinted locus at 6q24. The cardinal features are: severe intrauterine growth retardation, hyperglycemia that begins in the neonatal period in a term infant and resolves by age 18 months, dehydration, and absence of ketoacidosis. Macroglossia and umbilical hernia may be present. 6q24-TNDM associated with a multilocus imprinting disturbance (MLID) can be associated with marked hypotonia, congenital heart disease, deafness, neurologic features including epilepsy, and renal malformations. Diabetes mellitus usually starts within the first week of life and lasts on average three months but can last longer than a year. Although insulin is usually required initially, the need for insulin gradually declines over time. Intermittent episodes of hyperglycemia may occur in childhood, particularly during intercurrent illnesses. Diabetes mellitus may recur in adolescence or later in adulthood. Women who have had 6q24-TNDM are at risk for relapse during pregnancy.
Disease that is characterised by moderate thrombocytopenia, abnormal platelet function and the propensity to develop myeloid malignancies, in particular acute myelogenous leukaemia. The prevalence is unknown but the disease has been reported in less than 20 families. Causative mutations have been identified in the RUNX1 gene (also known as AML1 or CBFA2; chromosome 21q22.3) in most of the analysed families. The condition is inherited as an autosomal dominant trait.
A rare multiple congenital anomalies syndrome with mild to severe intellectual disability, a distinctive facial gestalt (blepharophimosis, maxillary hypoplasia, telecanthus, microtia and atresia of the external auditory meatus) as well as skeletal and articular abnormalities (e.g. camptodactyly of the fingers, cutaneous syndactyly, talipes equinovarus, flexion contractures of the proximal interphalangeal joints, hip or elbow subluxation, joint laxity). May also present with neonatal hypotonia, variable respiratory manifestations, chronic feeding difficulties and gray matter heterotopia.
Type 1 diabetes is a disorder characterized by abnormally high blood sugar levels. In this form of diabetes, specialized cells in the pancreas called beta cells stop producing insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Lack of insulin results in the inability to use glucose for energy or to control the amount of sugar in the blood.Type 1 diabetes can occur at any age; however, it usually develops by early adulthood, most often starting in adolescence. The first signs and symptoms of the disorder are caused by high blood sugar and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet, and weight loss. These symptoms may recur during the course of the disorder if blood sugar is not well controlled by insulin replacement therapy. Improper control can also cause blood sugar levels to become too low (hypoglycemia). This may occur when the body's needs change, such as during exercise or if eating is delayed. Hypoglycemia can cause headache, dizziness, hunger, shaking, sweating, weakness, and agitation.Uncontrolled type 1 diabetes can lead to a life-threatening complication called diabetic ketoacidosis. Without insulin, cells cannot take in glucose. A lack of glucose in cells prompts the liver to try to compensate by releasing more glucose into the blood, and blood sugar can become extremely high. The cells, unable to use the glucose in the blood for energy, respond by using fats instead. Breaking down fats to obtain energy produces waste products called ketones, which can build up to toxic levels in people with type 1 diabetes, resulting in diabetic ketoacidosis. Affected individuals may begin breathing rapidly; develop a fruity odor in the breath; and experience nausea, vomiting, facial flushing, stomach pain, and dryness of the mouth (xerostomia). In severe cases, diabetic ketoacidosis can lead to coma and death.Over many years, the chronic high blood sugar associated with diabetes may cause damage to blood vessels and nerves, leading to complications affecting many organs and tissues. The retina, which is the light-sensitive tissue at the back of the eye, can be damaged (diabetic retinopathy), leading to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) may also occur and can lead to kidney failure and end-stage renal disease (ESRD). Pain, tingling, and loss of normal sensation (diabetic neuropathy) often occur, especially in the feet. Impaired circulation and absence of the normal sensations that prompt reaction to injury can result in permanent damage to the feet; in severe cases, the damage can lead to amputation. People with type 1 diabetes are also at increased risk of heart attacks, strokes, and problems with urinary and sexual function.
This syndrome has characteristics of craniosynostosis, intellectual deficit, short stature, facial dysmorphism (oval face with almond-shaped palpebral fissures, droopy eyelids and a small nose) and minor distal anomalies. It has been described in 10 patients. Transmission is autosomal dominant and the syndrome is associated with partial duplication of the long arm of chromosome 5 (5q35-5qter).
Crisponi syndrome, the infantile presentation of cold-induced sweating syndrome (CISS), is characterized by dysmorphic features (distinctive facies, lower facial weakness, flexion deformity at the elbows, camptodactyly with fisted hands, misshapen feet, and overriding toes), poor suck reflex and severely impaired swallowing, and temperature spikes associated with an increased risk for seizures and sudden death. During the first decade of life, children with CISS develop profuse sweating of the face, arms, and chest with ambient temperatures below 18º to 22º C, and with other stimuli including apprehension or ingestion of sweets. Affected individuals sweat very little in hot environments and may feel overheated. In the second decade, progressive thoracolumbar kyphoscoliosis requires intervention.
A type of age-related cataract that primarily affects the nucleus of the lens.
DFNA9 is an autosomal dominant adult-onset form of progressive sensorineural hearing loss associated with variable vestibular dysfunction (summary by Robertson et al., 2006).
A congenital condition caused by a deletion on the short arm of chromosome 10p13-p14. The NEBL gene, encoding nebulette, a heart-specific component of the sarcomere, may be responsible for the clinical findings. The condition is characterized by immunodeficiency, unusual facies, congenital heart anomalies (tetralogy of Fallot, pulmonary atresia with ventricular septal defect, truncus arteriosus, interrupted aortic arch, isolated anomalies of the aortic arch, and ventricular septal defect), hypoparathyroidism, and increased susceptibility to infections.
Syndrome with characteristics of absence of the upper limbs and severe underdevelopment of the lower limbs. Minor facial abnormalities (depressed nasal root, upturned nose, infra-orbital creases, prominent cheeks and micrognathia) were also reported. The syndrome has been described in three fetuses born to non-consanguineous parents.
Brachial amelia, cleft lip, and holoprosencephaly (ACLH) is a severe multiple congenital anomaly disorder characterized by brachial amelia, cleft lip, and forebrain defects consistent with holoprosencephaly. Although the disorder is rarely reported, the features are consistent enough to constitute a distinct entity (summary by Kariminejad et al., 2009).
This syndrome has characteristics of sensorineural deafness, short stature, femoral epiphyseal dysplasia, umbilical and inguinal hernias and developmental delay (growth retardation and mild intellectual deficit). It has been described in two brothers born to consanguineous parents. They also have dysmorphic features (triangular face, pointed chin) and bilateral obstruction of lacrimal ducts. This syndrome is transmitted as an autosomal recessive trait.
This syndrome has characteristics of short stature presenting in the neonatal period, associated with osteochondrodysplastic lesions and facial dysmorphism. It has been described in two members from the same family.
The Martinez-Frias syndrome is characterized by pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia or hypoplasia, with or without tracheoesophageal fistula. There is considerable phenotypic overlap between Martinez-Frias syndrome and Mitchell-Riley syndrome (MTCHRS; 615710), the latter being characterized by neonatal diabetes in addition to the features of the Martinez-Frias syndrome, but without tracheoesophageal fistula (Smith et al., 2010).
A rare disorder with manifestation of hypo or oligodontia and acanthosis nigricans. It has been described in four generations of one family. Onset generally occurs during adolescence. Some patients are born with multiple teeth. Hair anomalies (sparse body and scalp hair) also reported. Inheritance is autosomal dominant.
Decreased density/number and/or decreased diameter of eyebrow hairs.
Excessive growth of the bones of cranium, i.e., of the skull.
ATP1A3-related neurologic disorders represent a clinical continuum in which at least three distinct phenotypes have been delineated: rapid-onset dystonia-parkinsonism (RDP); alternating hemiplegia of childhood (ACH); and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS). However, some affected individuals have intermediate phenotypes or only a few features that do not fit well into one of these major phenotypes. RDP has been characterized by: abrupt onset of dystonia over days to weeks with parkinsonism (primarily bradykinesia and postural instability); common bulbar involvement; and absence or minimal response to an adequate trial of L-dopa therapy, with few exceptions. Often fever, physiologic stress, or alcoholic binges trigger the onset of symptoms. After their initial appearance, symptoms often stabilize with little improvement; occasionally second episodes occur with abrupt worsening of symptoms. Rarely, affected individuals have reported a more gradual onset of symptoms over weeks to months. Anxiety, depression, and seizures have been reported. Age of onset ranges from four to 55 years, although a childhood variation of RDP with onset between ages nine and 14 months has been reported. AHC is a complex neurodevelopmental syndrome most frequently manifesting in infancy or early childhood with paroxysmal episodic neurologic dysfunction including alternating hemiparesis or dystonia, quadriparesis, seizure-like episodes, and oculomotor abnormalities. Episodes can last for minutes, hours, days, or even weeks. Remission of symptoms occurs with sleep and immediately after awakening. Over time, persistent neurologic deficits including oculomotor apraxia, ataxia, choreoathetosis, dystonia, parkinsonism, and cognitive and behavioral dysfunction develop in the majority of those affected; more than 50% develop epilepsy in addition to their episodic movement disorder phenotype. CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome is characterized by episodes of ataxic encephalopathy and/or weakness during and after a febrile illness. Onset is between ages six months and four years. Some acute symptoms resolve; progression of sensory losses and severity vary.
Autosomal dominant deafness-11 is a nonsyndromic form of progressive neurosensory hearing loss with postlingual onset. Some affected individuals have mild vestibular symptoms (summary by Sun et al., 2011).
Hereditary hemorrhagic telangiectasia is a disorder that results in the development of multiple abnormalities in the blood vessels.In the circulatory system, blood carrying oxygen from the lungs is normally pumped by the heart into the arteries at high pressure. The pressure allows the blood to make its way through the arteries to the smaller vessels (arterioles and capillaries) that supply oxygen to the body's tissues. By the time blood reaches the capillaries, the pressure is much lower. The blood then proceeds from the capillaries into veins, through which it eventually returns to the heart.In hereditary hemorrhagic telangiectasia, some arterial vessels flow directly into veins rather than into the capillaries. These abnormalities are called arteriovenous malformations. When they occur in vessels near the surface of the skin, where they are visible as red markings, they are known as telangiectases (the singular is telangiectasia).Without the normal buffer of the capillaries, the blood moves from the arteries at high pressure into the thinner walled, less elastic veins. The extra pressure tends to strain and enlarge these blood vessels, and may result in compression or irritation of adjacent tissues and frequent episodes of severe bleeding (hemorrhage). Nosebleeds are very common in people with hereditary hemorrhagic telangiectasia, and more serious problems may arise from hemorrhages in the brain, liver, lungs, or other organs.There are several forms of hereditary hemorrhagic telangiectasia, distinguished mainly by their genetic cause but with some differences in patterns of signs and symptoms. People with type 1 tend to develop symptoms earlier than those with type 2, and are more likely to have blood vessel malformations in the lungs and brain. Type 2 and type 3 may be associated with a higher risk of liver involvement. Women are more likely than men to develop blood vessel malformations in the lungs with type 1, and are also at higher risk of liver involvement with both type 1 and type 2. Individuals with any form of hereditary hemorrhagic telangiectasia, however, can have any of these problems.Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is a condition that involves both arteriovenous malformations and a tendency to develop growths (polyps) in the gastrointestinal tract. Hereditary hemorrhagic telangiectasia types 1, 2 and 3 do not appear to increase the likelihood of such polyps.
The caveolinopathies, a group of muscle diseases, can be classified into five phenotypes, which can be seen in different members of the same family: Limb-girdle muscular dystrophy 1C (LGMD1C), characterized by onset usually in the first decade, mild-to-moderate proximal muscle weakness, calf hypertrophy, positive Gower sign, and variable muscle cramps after exercise. Isolated hyperCKemia (i.e., elevated serum concentration of creatine kinase (CK) in the absence of signs of muscle disease) (HCK). Rippling muscle disease (RMD), characterized by signs of increased muscle irritability, such as percussion-induced rapid contraction (PIRC), percussion-induced muscle mounding (PIMM), and/or electrically silent muscle contractions (rippling muscle). Distal myopathy (DM), observed in one individual only Hypertrophic cardiomyopathy (HCM), without skeletal muscle manifestations.
Cerebellar ataxia Cayman type has characteristics of psychomotor retardation, hypotonia and cerebellar dysfunction (nystagmus, ataxic gait, truncal ataxia, dysarthric speech and intention tremor), associated with cerebellar hypoplasia. The prevalence is unknown, but the disorder is very rare in the general population. However, a founder mutation has led to a high incidence in the Cayman island population. The disorder is transmitted as an autosomal recessive trait and is caused by mutations in the ATCAY gene (19p13.3), encoding Caytaxin.
The hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas (CRC). Genetic Heterogeneity of Hereditary Mixed Polyposis HMPS2 (610069) is caused by mutation in the BMPR1A gene (601299) on chromosome 10q23.
Potocki-Shaffer syndrome is a rare contiguous gene deletion syndrome due to haploinsufficiency of the 11p12-p11.2 region and is characterized by craniofacial abnormalities, developmental delay, intellectual disability, multiple exostoses (168500), and biparietal foramina (605957) (summary by Swarr et al., 2010).
A form of syndromic craniosynostosis with characteristics of sagittal/dolichocephalic head shape with a relatively normal facial appearance and complete soft tissue syndactyly of hand and foot. Transmission is autosomal dominant with variable expression of the hand findings, and incomplete penetrance of the sagittal craniosynostosis.
Syndrome with characteristics of osteoporosis and congenital oculocutaneous hypopigmentation. Three cases have been described in the literature. The mode of inheritance appears to be autosomal recessive.
Dental anomalies and short stature (DASS) is characterized by significant short stature with brachyolmia as well as hypoplastic amelogenesis imperfecta with almost absent enamel (Huckert et al., 2015). Some patients exhibit valvular and/or vascular defects, including mitral valve prolapse, aortic root dilation, and aortic as well as other arterial aneurysms (Dugan et al., 2015; Guo et al., 2018). Inter- and intrafamilial variability has been reported.
The presence of one or more herniated nucleus pulposus of intervertebral disk.
A reduction of the distance between vertebral pedicles, which are the two short, thick processes, which project backward, one on either side, from the upper part of the vertebral body, at the junction of its posterior and lateral surfaces.
Keratoderma with woolly hair is a group of related conditions that affect the skin and hair and in many cases increase the risk of potentially life-threatening heart problems. People with these conditions have hair that is unusually coarse, dry, fine, and tightly curled. In some cases, the hair is also sparse. The woolly hair texture typically affects only scalp hair and is present from birth. Starting early in life, affected individuals also develop palmoplantar keratoderma, a condition that causes skin on the palms of the hands and the soles of the feet to become thick, scaly, and calloused.Cardiomyopathy, which is a disease of the heart muscle, is a life-threatening health problem that can develop in people with keratoderma with woolly hair. Unlike the other features of this condition, signs and symptoms of cardiomyopathy may not appear until adolescence or later. Complications of cardiomyopathy can include an abnormal heartbeat (arrhythmia), heart failure, and sudden death.Keratoderma with woolly hair comprises several related conditions with overlapping signs and symptoms. Researchers have recently proposed classifying keratoderma with woolly hair into four types, based on the underlying genetic cause. Type I, also known as Naxos disease, is characterized by palmoplantar keratoderma, woolly hair, and a form of cardiomyopathy called arrhythmogenic right ventricular cardiomyopathy (ARVC). Type II, also known as Carvajal syndrome, has hair and skin abnormalities similar to type I but features a different form of cardiomyopathy, called dilated left ventricular cardiomyopathy. Type III also has signs and symptoms similar to those of type I, including ARVC, although the hair and skin abnormalities are often milder. Type IV is characterized by palmoplantar keratoderma and woolly and sparse hair, as well as abnormal fingernails and toenails. Type IV does not appear to cause cardiomyopathy.
Anterior polar cataracts are small opacities on the anterior surface of the lens. They usually do not interfere with vision (Moross et al., 1984). The preferred title/symbol of this entry was formerly 'Cataract, Anterior Polar, 2; CTAA2.'
Neonatal severe hyperparathyroidism usually manifests in the first 6 months of life with severe hypercalcemia, bone demineralization, and failure to thrive. Early diagnosis is critical because untreated NSHPT can be a devastating neurodevelopmental disorder, which in some cases is lethal without parathyroidectomy. Some infants have milder hyperparathyroidism and a substantially milder clinical presentation and natural history (summary by Egbuna and Brown, 2008).
Garfield and Karaplis (2001) reviewed the various causes and clinical forms of hypoparathyroidism. They noted that hypoparathyroidism is a clinical disorder characterized by hypocalcemia and hyperphosphatemia. It manifests when parathyroid hormone (PTH; 168450) secreted from the parathyroid glands is insufficient to maintain normal extracellular fluid calcium concentrations or, less commonly, when PTH is unable to function optimally in target tissues, despite adequate circulating levels. Congenital absence of the parathyroid and thymus glands (III and IV pharyngeal pouch syndrome, or DiGeorge syndrome, 188400) is usually a sporadic condition (Taitz et al., 1966).
Autosomal dominant spastic paraplegia-9A is a neurologic disorder characterized by onset of slowly progressive spasticity mainly affecting the lower limbs. The age at onset usually ranges from adolescence to adulthood, and patients have gait difficulties, motor neuropathy, and dysarthria. Additional variable features include cerebellar signs, cataract, pes cavus, and urinary urgency (summary by Coutelier et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
Brachydactyly type A2 is an autosomal dominant disorder characterized by malformations of the middle phalanx of the index finger and by anomalies of the second toe (summary by Su et al., 2011).
A rare disorder characterised by tetralogy of Fallot, minor facial anomalies, and severe intellectual deficiency and growth delay. Dysmorphic features include large, protruding, abnormally modelled ears and broad nasal root. Microcephaly and syndactyly of second and third toes have also been recorded. All patients have severe intellectual deficiency. The condition is transmitted as an autosomal recessive trait.
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). CDG1D is a type I CDG that generally presents with severe neurologic involvement associated with dysmorphism and visual impairment. Liver involvement is sometimes present (summary by Marques-da-Silva et al., 2017). For a discussion of the classification of CDGs, see CDG1A (212065).
Hereditary hemorrhagic telangiectasia (HHT) is characterized by the presence of multiple arteriovenous malformations (AVMs) that lack intervening capillaries and result in direct connections between arteries and veins. The most common clinical manifestation is spontaneous and recurrent nosebleeds (epistaxis) beginning on average at age 12 years. Telangiectases (small AVMs) are most evident on the lips, tongue, buccal mucosa, face, chest, and fingers. The average age of onset is generally later than epistaxis, but may be during childhood. Large AVMs often cause symptoms when they occur in the lungs, liver, or brain; complications from bleeding or shunting may be sudden and catastrophic. Approximately 25% of individuals with HHT have GI bleeding, which most commonly begins after age 50 years.
Ayme-Gripp syndrome is a clinically homogeneous phenotype characterized by congenital cataracts, sensorineural hearing loss, intellectual disability, seizures, brachycephaly, a distinctive flat facial appearance, and reduced growth (Niceta et al., 2015).
OTOF-related deafness (DFNB9 nonsyndromic hearing loss) is characterized by two phenotypes: prelingual nonsyndromic hearing loss and, less frequently, temperature-sensitive nonsyndromic auditory neuropathy (TS-NSAN). The nonsyndromic hearing loss is bilateral severe-to-profound congenital deafness. In the first one or two years of life, OTOF-related deafness can appear to be an auditory neuropathy based on electrophysiologic testing in which auditory brain stem responses (ABRs) are absent and otoacoustic emissions (OAEs) are present. However, with time OAEs disappear and electrophysiologic testing is more consistent with a cochlear defect. The distinction between auditory neuropathy and a cochlear defect is important as cochlear implants may be of marginal value in persons with auditory neuropathy but have been shown to be effective for individuals with OTOF-related deafness. TS-NSAN is characterized by normal-to-mild hearing loss in the absence of fever and significant hearing loss ranging from severe to profound in the presence of fever. When the fever resolves, hearing returns to normal.
Absence of the acoustic reflex, an involuntary contraction of the stapedius muscle that occurs in response to high-intensity sound stimuli.
Familial cortical myoclonic tremor associated with epilepsy (FCMTE) is characterized by an autosomal dominant inheritance, adult-onset cortical myoclonus, and seizures in 40% of patients. Myoclonus is usually the first symptom and is characterized by tremulous finger movements and myoclonus of the extremities (summary by Depienne et al., 2010). FAME1 tends to occur in patients of Japanese or Han Chinese descent (summary by Cen et al., 2018). Genetic Heterogeneity of Familial Adult Myoclonic Epilepsy See also FAME2 (607876), caused by mutation in the ADRA2B gene (104260) on chromosome 2q11; FAME3 (613608), which maps to chromosome 5p15; FAME4 (615127), which maps to chromosome 3q26.32-q28; FAME5 (615400), caused by mutation in the CNTN2 gene (190197) on chromosome 1q32; FAME6 (618074), caused by mutation in the TNRC6A gene (610739) on chromosome 16p12; and FAME7 (618075), caused by mutation in the RAPGEF2 gene (609530) on chromosome 4. Progressive myoclonic epilepsy is a more severe disorder (see, e.g., EPM1, 254800).
The phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS) is now known to be a continuum that includes the classic phenotype as well as paroxysmal exercise-induced dyskinesia and epilepsy (previously known as dystonia 18 [DYT18]) and paroxysmal choreoathetosis with spasticity (previously known as dystonia 9 [DYT9]), atypical childhood absence epilepsy, myoclonic astatic epilepsy, and paroxysmal non-epileptic findings including intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia. The classic phenotype is characterized by infantile-onset seizures, delayed neurologic development, acquired microcephaly, and complex movement disorders. Seizures in classic early-onset Glut1 DS begin before age six months. Several seizure types occur: generalized tonic or clonic, focal, myoclonic, atypical absence, atonic, and unclassified. In some infants, apneic episodes and abnormal episodic eye-head movements similar to opsoclonus may precede the onset of seizures. The frequency, severity, and type of seizures vary among affected individuals and are not related to disease severity. Cognitive impairment, ranging from learning disabilities to severe intellectual disability, is typical. The complex movement disorder, characterized by ataxia, dystonia, and chorea, may occur in any combination and may be continuous, paroxysmal, or continual with fluctuations in severity influenced by environmental factors such as fasting or with infectious stress. Symptoms often improve substantially when a ketogenic diet is started.
Sporadic hemiplegic migraine is a rare form of migraine headache. Migraines typically cause intense, throbbing pain in one area of the head. Some people with migraines also experience nausea, vomiting, and sensitivity to light and sound. These recurrent headaches typically begin in childhood or adolescence and can be triggered by certain foods, emotional stress, and minor head trauma. Each headache may last from a few hours to a few days.In sporadic hemiplegic migraine and some other types of migraine, a pattern of neurological symptoms called an aura occurs before onset of the headache. An aura commonly includes temporary visual changes such as blind spots (scotomas), flashing lights, zig-zagging lines, and double vision. In people with sporadic hemiplegic migraine, auras are also characterized by temporary numbness or weakness, often affecting one side of the body (hemiparesis). Additional features of an aura can include difficulty with speech, confusion, and drowsiness. An aura typically develops gradually over a few minutes and lasts about an hour.Some people with sporadic hemiplegic migraine experience unusually severe migraine episodes. These episodes can include fever, prolonged weakness, seizures, and coma. Although most people with sporadic hemiplegic migraine recover completely between episodes, neurological symptoms such as memory loss and problems with attention can last for weeks or months. Some affected individuals develop mild but permanent difficulty coordinating movements (ataxia), which may worsen with time, and rapid, involuntary eye movements called nystagmus. Mild to severe intellectual disability has been reported in some people with sporadic hemiplegic migraine.
Timothy syndrome is a multisystem disorder characterized by cardiac, hand/foot, facial, and neurodevelopmental features. Typical cardiac findings include a rate-corrected QT interval >480 ms, functional 2:1 AV block with bradycardia, tachyarrhythmias, and congenital heart defects (patent ductus arteriosus, patent foramen ovale, ventricular septal defect, tetralogy of Fallot, hypertrophic cardiomyopathy). The diagnosis of Timothy syndrome is generally made within the first few days of life although it may be suspected prenatally due to 2:1 AV block or bradycardia in the fetus. Hand/foot findings are unilateral or bilateral cutaneous syndactyly variably involving fingers two (index), three (middle), four (ring), and five (little) and bilateral cutaneous syndactyly of toes two and three. Facial findings include depressed nasal bridge, low-set ears, thin vermilion border of the upper lip, and round face. Neuropsychiatric involvement includes global developmental delays and autism spectrum disorders. Ventricular tachyarrhythmia is the leading cause of death, followed by infection and complications of intractable hypoglycemia. Average age of death is 2.5 years.
Brody myopathy, a disorder of fast-twitch skeletal muscle function, is characterized by exercise-induced impairment of skeletal muscle relaxation, stiffening, and cramps, predominantly in the arms, legs, and eyelids (summary by Odermatt et al., 2000).
A rare genetic renal malformation syndrome with characteristics of variable degrees of malformation in the pelvicalyceal system (including unilateral or bilateral calyceal dilatation, infundibular stenosis, hypoplasia or stenosis of the renal pelvis) which lead to multicystic kidney. Clinically it exhibits abdominal, lumbar or flank pain, recurrent urinary tract infections, hypertension, proteinuria and often progresses to renal insufficiency. Calyceal dilatation and hydronephrosis are frequently seen on imaging.
Primary congenital glaucoma (PCG) is characterized by elevated intraocular pressure (IOP), enlargement of the globe (buphthalmos), edema, and opacification of the cornea with rupture of Descemet's membrane (Haab’s striae), thinning of the anterior sclera and iris atrophy, anomalously deep anterior chamber, and structurally normal posterior segment except for progressive glaucomatous optic atrophy. Symptoms include photophobia, blepharospasm, and excessive tearing. Typically, the diagnosis is made in the first year of life. Depending on when treatment is instituted, visual acuity may be reduced and/or visual fields may be restricted. In untreated individuals, blindness invariably occurs.
Bony outgrowths that extend laterally from the margin of the metaphysis.
Autosomal dominant multiple epiphyseal dysplasia (MED) presents in early childhood, usually with pain in the hips and/or knees after exercise. Affected children complain of fatigue with long-distance walking. Waddling gait may be present. Adult height is either in the lower range of normal or mildly shortened. The limbs are relatively short in comparison to the trunk. Pain and joint deformity progress, resulting in early-onset osteoarthritis, particularly of the large weight-bearing joints.
Abnormally low level of cortisol in the blood.
Permanent neonatal diabetes mellitus (PNDM) is characterized by the onset of hyperglycemia within the first six months of life (mean age: 7 weeks; range: birth to 26 weeks). The diabetes mellitus is associated with partial or complete insulin deficiency. Clinical manifestations at the time of diagnosis include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. Therapy with insulin corrects the hyperglycemia and results in dramatic catch-up growth. The course of PNDM varies by genotype.
A kind of congenital cataract that is characterized by a hollow sphere of punctate opacities involving the fetal nucleus and that usually occurs bilaterally.
Van den Ende-Gupta syndrome is an autosomal recessive disorder characterized by severe contractual arachnodactyly from birth and distinctive facial dysmorphism, including triangular face, malar hypoplasia, narrow nose, everted lips, and blepharophimosis. Skeletal anomalies include slender ribs, hooked clavicles, and dislocated radial head. There is no neurologic involvement (summary by Patel et al., 2014).
Underdevelopment of the distal portion of the ulna.
Incisors with a thick marginal ridge surrounding a deep lingual fossa are termed shovel-shaped incisors.
Delay in cutaneous immune reaction to specific antigens mediated not by antibodies but by cells. The delayed hypersensitivity test is an immune function test measuring the presence of activated T cells that recognize a specific antigen and is performed by injecting a small amount of the antigen into the skin. The area of the injection is examined 48-72 hours thereafter.
Absence of the fingerlike protrusive, actin-dependent structures found on the surface of peripheral blood lymphocytes.
Average platelet volume below the lower limit of the normal reference interval.
Hyperferritinemia-cataract syndrome is a disorder characterized by an excess of an iron storage protein called ferritin in the blood (hyperferritinemia) and tissues of the body. A buildup of this protein begins early in life, leading to clouding of the lenses of the eyes (cataracts). In affected individuals, cataracts usually develop in infancy, rather than after age 60 as typically occurs in the general population. Cataracts that are not removed surgically cause progressive dimming and blurriness of vision because the clouded lenses reduce and distort incoming light.Although the hyperferritinemia in this disorder does not usually cause any health problems other than cataracts, the elevated ferritin levels in the blood can be mistaken for a sign of certain liver disorders. These conditions result in excess iron in the body and may be treated by blood-drawing. However, individuals with hyperferritinemia-cataract syndrome do not have an excess of iron, and with repeated blood draws will develop reduced iron levels leading to a low number of red blood cells (anemia). Therefore, correct diagnosis of hyperferritinemia-cataract syndrome is important to avoid unnecessary treatments or invasive test procedures such as liver biopsies.
Spontaneous detachment (amputation) of an appendage from the body.
Toenail changes apart from changes of the color of the toenail (nail dyschromia) that involve partial or complete disruption of the various keratinous layers of the nail plate.
Mutations in the CRYBA1 gene have been found to cause multiple types of cataract, which have been described as congenital zonular with sutural opacities, congenital nuclear progressive, and progressive lamellar. The preferred title/symbol of this entry was formerly 'Cataract, Congenital Zonular, with Sutural Opacities; CCZS.'
JAK3-deficient severe combined immunodeficiency (SCID) is an inherited disorder of the immune system. Individuals with JAK3-deficient SCID lack the necessary immune cells to fight off certain bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. Often the organisms that cause infection in people with JAK3-deficient SCID are described as opportunistic because they ordinarily do not cause illness in healthy people. Affected infants typically develop chronic diarrhea, a fungal infection in the mouth called oral thrush, pneumonia, and skin rashes. Persistent illness also causes affected individuals to grow more slowly than other children. Without treatment, people with JAK3-deficient SCID usually live only into early childhood.
Chromosome 3-linked frontotemporal dementia (FTD3) has been described in a single family from Denmark and in one individual with familial FTD3 from Belgium. It typically starts between ages 46 and 65 years with subtle personality changes and slowly progressive behavioral changes, dyscalculia, and language disturbances. Disinhibition or loss of initiative is the most common presenting symptom. The disease progresses over a few years into profound dementia with mutism. Several individuals have developed an asymmetric akinetic rigid syndrome with arm and gait dystonia and pyramidal signs that may be related to treatment with neuroleptic drugs. Disease duration may be as short as three years or longer than 20 years.
Primitive reflexes traditionally held to be a sign of disorders that affect the frontal lobes.
An early-onset chorioretinal dystrophy with characteristics of large atrophic macular and nasal retinal lesions, nystagmus, myopia, poor vision and slow disease progression. It has been described in two large families. Transmission is autosomal dominant and the causative gene has been mapped to a region on chromosome 6q, close to the macular dystrophy retinal 1 (MCDR1) locus.
Abnormal thinning of the cortical region of bones.
A generalized decrease in bone mineral density.
A morphological abnormality of epiphyses whereby they are abnormally outwardly curving (protuberant).
A very rare multiple congenital anomaly syndrome with characteristics of anophthalmia or severe microphthalmia, cleft lip/palate, facial cleft and sacral neural tube defects, along with various additional anomalies including congenital glaucoma, iris coloboma, primary hyperplastic vitreous, hypertelorism, low-set ears, clinodactyly, choanal atresia/stenosis, dysgenesis of sacrum, tethering of spinal cord, syringomyelia, hypoplasia of corpus callosum, cerebral ventriculomegaly and endocrine abnormalities. An autosomal recessive inheritance has been suggested.
A kind of craniosynostosis affecting the lambdoidal suture.
Any abnormal alteration of an individuals cricadian rhythm that affects the timing of sleeping and being awake.
GNE-related myopathy, also known as inclusion body myopathy 2, is characterized by slowly progressive distal muscle weakness that begins in the late teens to early adult years with gait disturbance and foot drop secondary to anterior tibialis muscle weakness. Weakness eventually includes the hand and thigh muscles but commonly spares the quadriceps muscles, even in advanced disease. Affected individuals are usually wheelchair bound about 20 years after onset. If quadriceps sparing is incomplete, loss of ambulation tends to occur earlier.
A very rare multiple congenital anomalies syndrome with short stature, facial dysmorphism (elongated face, hypertelorism, broad and high nasal bridge, mild epicanthus, posteriorly angulated ears, narrow and high-arched palate), skeletal anomalies (mesomelic brachymelia, short broad hands, prominent finger pads, short stubby thumbs, hyperextensibility of small joints, small feet), hypernasality and normal intelligence. Delayed bone age has also been reported.
Monogenic diabetes caused by inactivating mutation(s) in the PDX1 gene, encoding pancreas/duodenum homeobox protein 1. Homozygous PDX1 mutations result in permanent neonatal diabetes.
An increased concentration of 2-hydroxyglutaric acid in the urine.
Cerebral cysts, usually located in the wall of the caudate nucleus or in the caudothalamic groove. They are found in up to 5.2% of all neonates, using transfontanellar ultrasound in the first days of life.
Satoyoshi syndrome is a rare disorder characterized by progressive, painful, intermittent muscle spasms, diarrhea or unusual malabsorption, endocrinopathy with amenorrhea, and secondary skeletal abnormalities. The disorder is also called komuragaeri disease by the Japanese; in Japanese 'komura' means calf and 'gaeri' means 'turnover' or spasm. All cases have apparently been sporadic, even when occurring in large families (Ehlayel and Lacassie, 1995).
Hereditary nonpolyposis colorectal cancer type 5 is a cancer predisposition syndrome characterized by onset of colorectal cancer and/or extracolonic cancers, particularly endometrial cancer, usually in mid-adulthood. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by Castellsague et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of hereditary nonpolyposis colorectal cancer (HNPCC), see HNPCC1 (120435).
Microtia-anotia (M-A) can occur either as an isolated defect or in association with other defects. Only in a minority of cases has a genetic or environmental cause been found; in these cases, M-A is usually part of a specific pattern of multiple congenital anomalies. For instance, M-A is an essential component of isotretinoin embryopathy (243440), is an important manifestation of thalidomide embryopathy, and can be part of the prenatal alcohol syndrome and maternal diabetes embryopathy. M-A occurs with a number of single gene disorders, such as Treacher Collins syndrome (154500), branchiotorenal/branchiootic syndromes (see 113650 and 602588), oculoauricular syndrome (612109), microtia with hearing impairment and cleft palate (612290), or chromosomal syndromes, such as trisomy 18. M-A also occurs as part of seemingly nonrandom patterns of multiple defects, such as Goldenhar syndrome (164210) (Mastroiacovo et al., 1995). Alasti and Van Camp (2009) reviewed the genetics of microtia and microtia-associated syndromes and discussed their clinical aspects in relation to the causative genes. They stated that the estimated prevalence of microtia is 0.8 to 4.2 per 10,000 births, that it is more common in males, and that it can have a genetic or environmental predisposition.
Syndrome that is characterised by communicating hydrocephalus, endocardial fibroelastosis and congenital cataracts. It has been described in two children, both of whom died a few months after birth (the first as a result of a respiratory infection and the second due to cardiac complications). The aetiology of the syndrome is unknown but a viral or genetic origin has been proposed.
Paroxysmal extreme pain disorder, formerly known as familial rectal pain, is characterized by paroxysms of rectal, ocular, or submandibular pain with flushing. Onset is usually in the neonatal period or infancy (Fertleman et al., 2006).
An abnormally increased level of bone isoforms of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
Pacman dysplasia has characteristics of epiphyseal stippling and osteoclastic overactivity. It has been described in less than 10 patients but may be underdiagnosed. The syndrome may be inherited as an autosomal recessive trait. In order to make a definitive diagnosis, lysosomal storage should be investigated by electron microscopy, or enzyme assays should be performed. Familial recurrence can be easily detected by prenatal ultrasonography. This skeletal dysplasia is lethal.
Kleta (2006) reviewed aspects of renal stone disease. Nephrolithiasis and urolithiasis remain major public health problems of largely unknown cause. While disorders such as cystinuria (220100) and primary hyperoxaluria (see 259900) that have nephrolithiasis as a major feature have advanced understanding of the metabolic and physiologic processes of stone formation in general, they have not addressed the etiology of calcium oxalate stone formation, responsible for approximately 75% of urolithiasis cases in humans. Men are affected twice as often as women, but children show no such gender bias. The recurrence rate is also high. In populations of European ancestry, 5 to 10% of adults experience the painful precipitation of calcium oxalate in their urinary tracts. Thorleifsson et al. (2009) noted that between 35 and 65% of hypercalciuric stone formers and up to 70% of subjects with hypercalciuria have relatives with nephrolithiasis, and twin studies have estimated the heritability of kidney stones to be 56%.
Southeast Asian ovalocytosis is a hereditary red blood cell disorder that is widespread in certain ethnic groups of Malaysia, Papua New Guinea, the Philippines, and Indonesia. Ovalocytic erythrocytes are rigid and exhibit reduced expression of many erythrocyte antigens. The ovalocytes are resistant to invasion in vitro by several strains of malaria, including Plasmodium falciparum and Plasmodium knowlesi (summary by Jarolim et al., 1991). The disorder is most often asymptomatic but has been reported to be associated with signs of mild hemolysis such as intermittent jaundice and gallstones (summary by Reardon et al., 1993).
A rare genetic developmental defect during embryogenesis with characteristics of distinct facial features (long triangular face, broad forehead, narrow nose and mandible, high arched palate), prominent, dysmorphic ears (low-set and cup-shaped with large conchae and hypoplastic tragus, antitragus and lobe), long neck, preauricular and/or branchial fistulas and/or cysts, hypoplastic cervical muscles with sloping shoulders and clavicles, winged, low, and laterally-set scapulae, hearing impairment and mild intellectual deficit. Vertebral defects and short stature may also be associated.
Otodental syndrome is an autosomal dominant condition characterized by grossly enlarged canine and molar teeth (globodontia), associated with sensorineural hearing loss. Ocular coloboma segregating with otodental syndrome has been reported (summary by Gregory-Evans et al., 2007).
An exceedingly rare autosomal dominant disorder reported in only a few patients to date with characteristics of dacryocystitis due to lacrimal canal stenosis and osteopoikilosis (demonstrated radiologically as discrete spherical osteosclerotic lesions of 2-10 mm in diameter).
An increased resorption of bone matrix by osteoclasts leading to bony defects involving the tarsal bones.
Gnathodiaphyseal dysplasia is an autosomal dominant generalized skeletal syndrome characterized by cementoosseous lesions of the jawbones, in conjunction with bone fragility, bowing/cortical thickening of tubular bones, and diaphyseal sclerosis of long bones (summary by Marconi et al., 2013).
An elevation in bone density of the cortex of one or more diaphyses. Sclerosis is normally detected on a radiograph as an area of increased opacity.
Congenital onset bending or abnormal curvature of the femur that normalizes with age.
Abnormal reduction in ossification of the calvaria (roof of the skull consisting of the frontal bone, parietal bones, temporal bones, and occipital bone).
Syndrome characterised by the association of osteosarcoma, limb anomalies (clinodactyly with brachymesophalangia, bilateral radioulnar synostosis and absence of one digital ray of the foot) and red cell macrocytosis without anaemia. It has been described in three out of nine children from one family.
A congenital abnormality characterized by the underdevelopment of both optic nerves.
Autosomal dominant optic atrophy and cataract is an eye disorder that is characterized by impaired vision. Most affected individuals have decreased sharpness of vision (visual acuity) from birth, while others begin to experience vision problems in early childhood or later. In affected individuals, both eyes are usually affected equally. However, the severity of the vision loss varies widely, even among affected members of the same family, ranging from nearly normal vision to complete blindness.Several abnormalities contribute to impaired vision in people with autosomal dominant optic atrophy and cataract. In the early stages of the condition, affected individuals experience a progressive loss of certain cells within the retina, which is a specialized light-sensitive tissue that lines the back of the eye. The loss of these cells (known as retinal ganglion cells) is followed by the degeneration (atrophy) of the nerves that relay visual information from the eyes to the brain (optic nerves), which contributes to vision loss. Atrophy of these nerves causes an abnormally pale appearance (pallor) of the optic nerves, which can be seen only during an eye examination. Most people with this disorder also have clouding of the lenses of the eyes (cataracts). This eye abnormality can develop anytime but typically appears in childhood. Other common eye problems in autosomal dominant optic atrophy and cataract include involuntary movements of the eyes (nystagmus), or problems with color vision (color vision deficiency) that make it difficult or impossible to distinguish between shades of blue and green.Some people with autosomal dominant optic atrophy and cataract develop disturbances in the function of other nerves (neuropathy) besides the optic nerves. These disturbances can lead to problems with balance and coordination (cerebellar ataxia), an unsteady style of walking (gait), prickling or tingling sensations (paresthesias) in the arms and legs, progressive muscle stiffness (spasticity), or rhythmic shaking (tremors). In some cases, affected individuals have hearing loss caused by abnormalities of the inner ear (sensorineural deafness).
Complete blindness due to corneal opacities, difficult mastication due to temporomandibular fusion and anomalies of the arms. Micrognathia, shortening and bowing of the forearm, ulnar deviation and bowed radius, short fibula, genu valgum and coxa vara have been reported. Intelligence is normal. The causative gene has not yet been identified. Autosomal dominant inheritance has been suggested.
Hereditary distal onycholysis is an autosomal dominant nail disorder characterized by a decreased rate of growth of the nail, scleronychia, and a straight or concave proximal edge of detachment. Clinical features may include palmoplantar hyperhydrosis and marked sensitivity of the fingers to cold (summary by Bazex et al., 1990). Hereditary distal onycholysis is referred to here as nonsyndromic congenital nail disorder-5 (NDNC5). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
Odontoma-dysphagia syndrome is a malformation syndrome, with characteristics of odontomas and severe dysphagia. Less than ten cases have been reported so far. Three of the reported patients manifested multiple odontomas. Occasionally, cardiac, renal and hepatic involvement has been described. In several cases, autosomal dominant inheritance has been suspected. Currently, there are no genes associated with this condition.
Oculopharyngodistal myopathy (OPDM) is characterized by adult-onset of eye and facial muscle weakness, distal muscle weakness and atrophy, and pharyngeal involvement, resulting in dysphagia and dysarthria. There are variable manifestations of the disorder regarding muscle involvement and severity. Both autosomal recessive and autosomal dominant inheritance have been reported. OPDM is considered distinct from oculopharyngeal muscular dystrophy (OPMD; 164300), which is caused by mutation in the PABPN1 gene (602279) (summary by Durmus et al., 2011).
Congenital fusion (ankylosis) of the interphalangeal joint of the thumb.
Absence or underdevelopment (hypoplasia) of the middle phalanx of the little (5th) finger.
Schilbach-Rott syndrome is an autosomal dominant disorder characterized by hypotelorism, epicanthal folds, cleft palate, dysmorphic facies, and hypospadias in males. The phenotype is variable; mild mental retardation has been reported (summary by Shkalim et al., 2009).
Underdevelopment of one or more muscles innervated by the facial nerve (the seventh cranial nerve).
Thinned, deficient, or excessively arched ala nasi.
Excessive growth of the bones of the vertebral bodies.
Absence or underdevelopment (hypoplasia) of the middle phalanx of the fifth finger.
Syndactyly with fusion of toes three and four.
Classic congenital or infantile nystagmus presents as conjugate, horizontal oscillations of the eyes, in primary or eccentric gaze, often with a preferred head turn or tilt. Other associated features may include mildly decreased visual acuity, strabismus, astigmatism, and occasionally head nodding. Eye movement recordings reveal that infantile nystagmus is predominantly a horizontal jerk waveform, with a diagnostic accelerating velocity slow phase. However, pendular and triangular waveforms may also be present. The nystagmus may rarely be vertical. As these patients often have normal visual acuity, it is presumed that the nystagmus represents a primary defect in the parts of the brain responsible for ocular motor control; thus the disorder has sometimes been termed 'congenital motor nystagmus' (Tarpey et al., 2006; Shiels et al., 2007). For a discussion of genetic heterogeneity of congenital nystagmus, see NYS1 (310700).
A broad chest. [HPO:probinson, pmid:22368597]
An abnormality of one or more of the vertebrae. [HPO:probinson]
Sick sinus syndrome (also known as sinus node dysfunction) is a group of related heart conditions that can affect how the heart beats. ""Sick sinus"" refers to the sino-atrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally. In some cases, it does not produce the right signals to trigger a regular heartbeat. In others, abnormalities disrupt the electrical impulses and prevent them from reaching the rest of the heart.Sick sinus syndrome tends to cause the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia). In some cases, the heartbeat rapidly switches from being too fast to being too slow, a condition known as tachycardia-bradycardia syndrome. Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue). Once symptoms of sick sinus syndrome appear, they usually worsen with time. However, some people with the condition never experience any related health problems.Sick sinus syndrome occurs most commonly in older adults, although it can be diagnosed in people of any age. The condition increases the risk of several life-threatening problems involving the heart and blood vessels. These include a heart rhythm abnormality called atrial fibrillation, heart failure, cardiac arrest, and stroke.
Neuronal ceroid lipofuscinosis-4B is an autosomal dominant neurodegenerative disorder characterized by onset of symptoms in adulthood. It belongs to a group of progressive neurodegenerative diseases characterized by accumulation of intracellular autofluorescent lipopigment storage material in the brain and other tissues. Several different forms have been described according to age of onset (see, e.g., CLN3, 204200). Individuals with the adult form, sometimes referred to as Kufs disease, develop psychiatric manifestations, seizures, cerebellar ataxia, and cognitive decline. Retinal degeneration is usually not present (summary by Benitez et al., 2011 and Velinov et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
Spinal neurofibromatosis is an autosomal dominant disorder characterized by a high load of spinal tumors. These tumors may be asymptomatic or result in neurologic symptoms, including back pain, difficulty walking, and paresthesias. Spinal NF is considered to be a subtype of neurofibromatosis type I (NF1; 162200), which is an allelic disorder. Patients with spinal NF may or may not have the classic cutaneous cafe-au-lait pigmentary macules or ocular Lisch nodules typically observed in patients with classic NF1. Patients with spinal NF should be followed closely for spinal sequelae (summary by Burkitt Wright et al., 2013).
Multiple neurofibromas of the spinal nerve roots with a symmetric distribution.
The presence in the inguinal region (groin) of an increased number of freckles, small circular spots on the skin that are darker than the surrounding skin because of deposits of melanin.
Hereditary neuralgic amyotrophy (HNA) is characterized by sudden onset of severe, non-abating pain in the shoulder girdle and/or the upper limb and amyotrophy (muscle wasting or atrophy) that typically develops within two weeks of the onset of severe pain. Other sites may also be involved in an attack; sensory symptoms, present in the majority of affected individuals, can include hypoesthesia (decreased sensation) and paresthesias. Onset is typically in the second or third decade (median age 28 years). Although attacks appear to become less frequent with age, residual deficits accumulate with subsequent attacks. In some families, non-neurologic findings (characteristic craniofacial features, bifid uvula or cleft palate, short stature, and/or partial syndactyly of the fingers or toes) are present.
Mitochondrial DNA (mtDNA)-associated Leigh syndrome and NARP (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) are part of a continuum of progressive neurodegenerative disorders caused by abnormalities of mitochondrial energy generation. Leigh syndrome (or subacute necrotizing encephalomyelopathy) is characterized by onset of symptoms typically between ages three and 12 months, often following a viral infection. Decompensation (often with elevated lactate levels in blood and/or CSF) during an intercurrent illness is typically associated with psychomotor retardation or regression. Neurologic features include hypotonia, spasticity, movement disorders (including chorea), cerebellar ataxia, and peripheral neuropathy. Extraneurologic manifestations may include hypertrophic cardiomyopathy. About 50% of affected individuals die by age three years, most often as a result of respiratory or cardiac failure. NARP is characterized by proximal neurogenic muscle weakness with sensory neuropathy, ataxia, and pigmentary retinopathy. Onset of symptoms, particularly ataxia and learning difficulties, is often in early childhood. Individuals with NARP can be relatively stable for many years, but may suffer episodic deterioration, often in association with viral illnesses.
Thickening of the periosteum of long bone.
Adie (1926) first delineated narcolepsy as a separate and specific entity. It is a sleep disorder characterized by attacks of disabling daytime drowsiness and low alertness. The normal physiologic components of rapid eye movement (REM) sleep, dreaming and loss of muscle tone, are separated and also occur while the subject is awake, resulting in half-sleep dreams and episodes of skeletal muscle paralysis and atonia (cataplexy and sleep paralysis). Unlike normal sleep, that of narcolepsy often begins with REM activity and the time taken to fall asleep is shorter than normal. In contrast to animal models, human narcolepsy is not a simple genetic disorder. Most human cases of narcolepsy are sporadic and carry a specific HLA haplotype (Peyron et al., 2000). Familial cases are the exception rather than the rule, and monozygotic twins show only partial concordance (25 to 31%) (Mignot, 1998). Genetic Heterogeneity of Narcolepsy Additional narcolepsy loci have been mapped to chromosomes 4 (NRCLP2; 605841), 21q (NRCLP3; 609039), 22q13 (NRCLP4; 612417), 14q11 (NRCLP5; 612851), and 19p13.2 (NRCLP6; 614223). NRCLP7 (614250) is caused by mutation in the MOG gene (159465) on chromosome 6p22. Resistance to narcolepsy is associated with minor alleles of a SNP and a marker in the NLC1A gene (610259) on chromosome 21q22.
Underdevelopment of the glenoid fossa, which is the cavity in the lateral part of the scapula which articulates with the head of the humerus.
The presence of developmental dysplasia of the nail.
The presence of one or more obsessive-compulsive personality traits. Obsessions refer to persistent intrusive thoughts, and compulsions to intrusive behaviors, which the affected person experiences as involuntary, senseless, or repugnant.
Distal arthrogryposis is a clinically and genetically heterogeneous disorder characterized by clenched fist, overlapping fingers, camptodactyly, ulnar deviation, and positional foot deformities from birth. It is a disorder of primary limb malformation without primary neurologic or muscle disease. DA1 is not associated with other abnormalities, whereas other forms of DA have additional phenotypic features (Bamshad et al., 1996). The congenital contractures in DA2B (Sheldon-Hall syndrome, SHS) are similar to those observed in DA1, but affected individuals tend to have more prominent nasolabial folds, downslanting palpebral fissures, and a small mouth. DA2B is thought to be the most common of the distal arthrogryposis disorders (summary by Bamshad et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004). Genetic Heterogeneity of Susceptibility to Myopia MYP2 maps to chromosome 18p. Other myopia loci include MYP1 (310460) on Xq28; MYP3 (603221) on 12q21-q23; MYP5 (608474) on 17q21-q22; MYP6 (608908), caused by mutation in the SCO2 gene (602474) on 22q13; MYP7 (609256) on 11p13; MYP8 (609257) on 3q26; MYP9 (609258) on 4q12; MYP10 (609259) on 8p23; MYP11 (609994) on 4q22-q27; MYP12 (609995) on 2q37.1; MYP13 (300613) on Xq23-q27; MYP14 (610320) on 1p36; MYP15 (612717) on 10q21.1; MYP16 (612554) on 5p15.33-p15.2; MYP17 (formerly MYP4) (608367) on 7p15; MYP18 (255500) on chromosome 14q22-q24; MYP19 (613969) on 5p15.1-p13.3; MYP20 (614166) on 13q12.12; MYP21 (614167), caused by mutation in the ZNF644 gene (614159) on 1p22; MYP22 (615420), caused by mutation in the CCDC111 gene (615421) on 4q35; MYP23 (615431), caused by mutation in the LRPAP1 gene (104225) on 4p16; MYP24 (615946), caused by mutation in the SLC39A5 gene (608730) on 12q13; MYP25 (617238), caused by mutation in the P4HA2 gene (600608) on 5q31; and MYP26 (301010), caused by mutation in the ARR3 gene (301770) on Xq13.
An inherited neuromuscular disorder defined by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy. The exact prevalence remains unknown. Most commonly, the age of onset is in adolescence, although earlier presentations in infancy or childhood have been reported. Muscle weakness of variable severity is the major clinical manifestation. Mutations in the dynamin 2 (DNM2) gene on chromosome 19p13.2 are responsible.
A rare metabolic myopathy with characteristics of episodic myalgia with myoglobinuria which is induced by fever, viral or bacterial infection, prolonged exercise or alcohol abuse, and could, on occasion, lead to acute renal failure. Between episodes, patients may be asymptomatic or could present elevated creatine kinase levels and mild muscle weakness. There have been no further descriptions in the literature since 1997.
Myoclonus-dystonia (M-D) is a movement disorder characterized by a combination of rapid, brief muscle contractions (myoclonus) and/or sustained twisting and repetitive movements that result in abnormal postures (dystonia). The myoclonic jerks typical of M-D most often affect the neck, trunk, and upper limbs with less common involvement of the legs. Approximately 50% of affected individuals have additional focal or segmental dystonia, presenting as cervical dystonia and/or writer's cramp. Non-motor features may include obsessive-compulsive disorder (OCD), depression, anxiety, personality disorders, alcohol abuse, and panic attacks. Symptom onset is usually in childhood or early adolescence but ranges from age six months to 80 years. Most affected adults report a dramatic reduction in myoclonus in response to alcohol ingestion. M-D is compatible with an active life of normal span.
A myeloid proliferation occurring in newborns with Down syndrome. It is clinically and morphologically indistinguishable from acute myeloid leukemia and is associated with GATA1 mutations. The blasts display morphologic and immunophenotypic features of megakaryocytic lineage. In the majority of patients the myeloid proliferation undergoes spontaneous remission.
Perfect pitch, or absolute pitch (AP), is defined as the ability immediately and effortlessly to name a note or collection of notes when they are sounded. Often, persons with perfect pitch possess a memory capacity whereby they can remember the pitch of a note and the configuration of a group or series of notes after a significant interval of time has elapsed. These recognitive and memory talents involve a potential capacity for performing these functions together with a practice factor which is necessary for the maintenance of the skills at the highest level (summary by Profita and Bidder, 1988). Absolute pitch likely results from a combination of environmental and genetic factors (Theusch et al., 2009).
LGMD1 is an autosomal dominant disorder characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region. Distal muscle weakness may occur later. Daniele et al. (2007) provided a review of therapeutic strategies in various forms of LGMD, including ongoing studies in gene therapy. Genetic Heterogeneity of Autosomal Dominant Limb-Girdle Muscular Dystrophy Other forms of autosomal dominant LGMD include LGMD1B (159001), caused by mutation in the LMNA gene (150330) on chromosome 1q22; LGMD1C (607801), caused by mutation in the CAV3 gene (601253) on chromosome 3p25; LGMD1E (603511), caused by mutation in the DNAJB6 gene (611332) on chromosome 7q36; LGMD1F (608423), caused by mutation in the TNPO3 gene (610032) on chromosome 7q32; LGMD1G (609115), caused by mutation in the HNRNPDL gene (607137) on chromosome 4q21; and LGMD1H (613530), which maps to chromosome 3p25-p23. The symbol LGMD1D was formerly used for a disorder later found to be the same as desmin-related myopathy (601419).
Facioscapulohumeral muscular dystrophy (FSHD) typically presents before age 20 years with weakness of the facial muscles and the stabilizers of the scapula or the dorsiflexors of the foot. Severity is highly variable. Weakness is slowly progressive and approximately 20% of affected individuals eventually require a wheelchair. Life expectancy is not shortened.
Collagen VI-related myopathy is a group of disorders that affect skeletal muscles (which are the muscles used for movement) and connective tissue (which provides strength and flexibility to the skin, joints, and other structures throughout the body). Most affected individuals have muscle weakness and joint deformities called contractures that restrict movement of the affected joints and worsen over time. Researchers have described several forms of collagen VI-related myopathy, which range in severity: Bethlem myopathy is the mildest, an intermediate form is moderate in severity, and Ullrich congenital muscular dystrophy is the most severe.People with Bethlem myopathy usually have loose joints (joint laxity) and weak muscle tone (hypotonia) in infancy, but they develop contractures during childhood, typically in their fingers, wrists, elbows, and ankles. Muscle weakness can begin at any age but often appears in childhood to early adulthood. The muscle weakness is slowly progressive, with about two-thirds of affected individuals over age 50 needing walking assistance. Older individuals may develop weakness in respiratory muscles, which can cause breathing problems. Some people with this mild form of collagen VI-related myopathy have skin abnormalities, including small bumps called follicular hyperkeratosis on the arms and legs; soft, velvety skin on the palms of the hands and soles of the feet; and abnormal wound healing that creates shallow scars.The intermediate form of collagen VI-related myopathy is characterized by muscle weakness that begins in infancy. Affected children are able to walk, although walking becomes increasingly difficult starting in early adulthood. They develop contractures in the ankles, elbows, knees, and spine in childhood. In some affected people, the respiratory muscles are weakened, requiring people to use a machine to help them breathe (mechanical ventilation), particularly during sleep.People with Ullrich congenital muscular dystrophy have severe muscle weakness beginning soon after birth. Some affected individuals are never able to walk and others can walk only with support. Those who can walk often lose the ability, usually in adolescence. Individuals with Ullrich congenital muscular dystrophy develop contractures in their neck, hips, and knees, which further impair movement. There may be joint laxity in the fingers, wrists, toes, ankles, and other joints. Some affected individuals need continuous mechanical ventilation to help them breathe. As in Bethlem myopathy, some people with Ullrich congenital muscular dystrophy have follicular hyperkeratosis; soft, velvety skin on the palms and soles; and abnormal wound healing.Individuals with collagen VI-related myopathy often have signs and symptoms of multiple forms of this condition, so it can be difficult to assign a specific diagnosis. The overlap in disease features, in addition to their common cause, is why these once separate conditions are now considered part of the same disease spectrum.
Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder characterized by degeneration of spinal cord motor neurons resulting in muscle weakness. SMALED shows autosomal dominant inheritance with muscle weakness predominantly affecting the proximal lower extremities (Harms et al., 2010). The most common form of SMA (see, e.g., SMA1, 253300) shows autosomal recessive inheritance and is due to mutation in the SMN1 gene (600354) on chromosome 5q. Genetic Heterogeneity of Lower Extremity-Predominant Spinal Muscular Atrophy See also SMALED2A (615290) and SMALED2B (618291), both of which are caused by mutation in the BICD2 gene (609797) on chromosome 9q22. SMALED2A and SMALED2B differ in age at onset and severity, with SMALED2B being more severe.
Distal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells in the spinal cord. It results in muscle weakness and affects movement, primarily in the legs.Onset of distal hereditary motor neuropathy, type II ranges from the teenage years through mid-adulthood. The initial symptoms of the disorder are cramps or weakness in the muscles of the big toe and later, the entire foot. Over a period of approximately 5 to 10 years, affected individuals experience a gradual loss of muscle tissue (atrophy) in the lower legs. They begin to have trouble walking and running, and eventually may have complete paralysis of the lower legs. The thigh muscles may also be affected, although generally this occurs later and is less severe.Some individuals with distal hereditary motor neuropathy, type II have weakening of the muscles in the hands and forearms. This weakening is less pronounced than in the lower limbs and does not usually result in paralysis.
Reduced intensity of muscle tendon reflexes in the lower limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping.
Distal hereditary motor neuronopathy type VIIa is an autosomal dominant neurologic disorder characterized by onset in the second decade of progressive distal muscle wasting and weakness affecting the upper and lower limbs and resulting in walking difficulties and hand grip. There is significant muscle atrophy of the hands and lower limbs. The disorder is associated with vocal cord paresis due to involvement of the tenth cranial nerve (summary by Barwick et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN, see HMN type I (HMN1; 182960).
Slightly pigmented smooth or warty papules that are flesh colored and found on the upper surface of hands and feet.
The presence of a malignant neoplasm of the genital system.
A soft tissue continuity in the anteroposterior axis between adjacent foot digits that involves at least half of the proximodistal length of one of the two involved digits; or, a soft tissue continuity in the A/P axis between two digits of the foot that does not meet the prior objective criteria.
Chromosomal mosaicism as described here refers to a tendency to chromosomal nondisjunction. See also premature chromatid separation (PCS; 176430), which may also predispose to chromosomal nondisjunction.
Mycobacterium tuberculosis latently infects approximately one-third of humanity and is comparable only to human immunodeficiency virus (HIV; see 609423) as a leading infectious cause of mortality worldwide. Obstacles for controlling TB infection include lengthy treatment regimens of 6 to 9 months, drug resistance, lack of a highly efficacious vaccine, and incomplete understanding of the factors that control infectivity and disease progression. Although only 10% of individuals infected with M. tuberculosis develop active disease, the immune responses associated with TB susceptibility or resistance are not known. In addition, it is not known why some individuals have disseminated TB that spreads to the meninges and central nervous system, while most people have localized disease in the lungs. A number of studies suggest that host genetic factors influence susceptibility and resistance to TB (review by Berrington and Hawn, 2007).
A very rare genetic overgrowth/obesity syndrome with characteristics of macrocephaly, obesity, mental (intellectual) disability and ocular abnormalities. Other frequent clinical signs include macrosomia, downslanting palpebral fissures, hypertelorism, broad nasal root, high and broad forehead and delay in bone maturation, in association with normal thyroid function and karyotype.
Mitral valve prolapse (MVP) has a prevalence of approximately 2 to 3% in the general population. It is characterized by fibromyxomatous changes in mitral leaflet tissue, with upward displacement of 1 or both leaflets into the left atrium during systole; MVP is diagnosed when the movement of the mitral leaflets exceeds 2 mm. In classic MVP, leaflets are at least 5 mm thick, whereas in nonclassic MVP, they are less than 5 mm thick. Auscultatory findings, when present, consist of a midsystolic click and/or a late systolic murmur. The natural history of MVP varies from benign, with a normal life expectancy, to severe complications associated with the development of significant mitral regurgitation, including congestive heart failure, bacterial endocarditis, atrial fibrillation, thromboembolism, and even sudden death. However, complications are uncommon, affecting less than 3% of individuals with MVP (Freed et al., 1999; Grau et al., 2007; Delling and Vasan, 2014). Grau et al. (2007) provided a detailed review of the genetics of mitral valve prolapse. Delling and Vasan (2014) reviewed the epidemiology and pathophysiology of MVP, with discussion of disease progression, genetics, and molecular basis. Genetic Heterogeneity of Familial Mitral Valve Prolapse Several loci for mitral valve prolapse (MVP) have been been mapped: MVP1 to chromosome 16p; MVP2 (607829) to chromosome 11p; and MVP3 (610840) to chromosome 13q.
The disorder of congenital mirror movements (CMM) is characterized by early-onset, obvious mirror movements (involuntary movements of one side of the body that mirror intentional movements on the opposite side) in individuals with no other clinical signs or symptoms. Although mirror movements vary in severity, most affected individuals have strong and sustained mirror movements of a lesser amplitude than the corresponding voluntary movements. Mirror movements usually persist throughout life, without deterioration or improvement, and are not associated with subsequent onset of additional neurologic manifestations.
A developmental defect characterized by fusion of the left and right halves of the thalamus. [HPO:probinson]
Truncus arteriosus (single great artery leaving the base of the heart, giving rise to the coronary, pulmonary, and systemic arteries) with a short pulmonary trunk arises from the truncus arteriosus, giving rise to both pulmonary arteries.
Frontal schisis (cleft or cleavage) of vertebral bodies.
Metaphyseal cupping affecting the proximal phalanges.
Increased cytoplasmic staining of fibroblasts with toluidine blue.
Kantaputra mesomelic dysplasia (MMDK) is a rare, autosomal dominant skeletal disease characterized by symmetric marked shortening of the upper and lower limbs. The ulnae are very short and the radii are bowed. The distal humerus has a dumbbell shape, whereas the hands are relatively normal but show progressive flexion contractures of the proximal interphalangeal joints. Carpal and tarsal synostoses are observed in some individuals. In the lower limbs, the feet are fixed in plantar flexion with the sole facing backward, causing 'ballerina-like standing.' The prominent distal fibula on the ventral aspect is considered to be the signature finding of the syndrome. The calcaneus is small or missing, and a small fibula and talus as well as fibulocalcaneal synostosis are characteristic features. The tibial bony knot articulates with the proximal end of the fibula (summary by Kantaputra et al., 2010). See 613681 for discussion of the chromosome 2q31.1 duplication syndrome, which shows cytogenetic and phenotypic overlap with MMDK.
An extremely rare tumor association characterized by dual predisposition to melanoma and neural system tumors (typically astrocytoma). Fewer than 20 affected families have been reported to date. Affected individuals had cutaneous melanoma in association with dysplastic nevi, astrocytoma, benign or malignant peripheral nerve sheath tumor, neurofibroma, medulloblastoma, glioblastoma multiforme, ependymoma, glioma, and meningioma. In some cases, melanoma was described first followed by nervous system tumors, and in other cases, melanoma was a secondary cancer. The etiology of this tumor association is unknown. Genetic mutations or germline deletions are thought to underlie this cancer susceptibility syndrome.
Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs most often in the skin, but may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes (summary by Habif, 2010). For a discussion of genetic heterogeneity of cutaneous malignant melanoma, see CMM1 (155600).
Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs most often in the skin, but may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes (summary by Habif, 2010). Genetic Heterogeneity of Susceptibility to Cutaneous Malignant Melanoma The locus for susceptibility to familial cutaneous malignant melanoma-1 (CMM1) has been mapped to chromosome 1p36. Other CMM susceptibility loci include CMM2 (155601), caused by variation in the CDKN2A gene (600160) on chromosome 9p21; CMM3 (609048), caused by variation in the CDK4 gene (123829) on chromosome 12q14; CMM4 (608035), mapped to chromosome 1p22; CMM5 (613099), caused by variation in the MC1R gene (155555) on chromosome 16q24; CMM6 (613972), caused by variation in the XRCC3 gene (600675) on chromosome 14q32; CMM7 (612263), mapped to chromosome 20q11; CMM8 (614456), caused by variation in the MITF gene (156845) on chromosome 3p13; CMM9 (615134), caused by variation in the TERT gene (187270) on chromosome 5p15; and CMM10 (615848), caused by mutation in the POT1 gene (606478) on chromosome 7q31. Somatic mutations causing malignant melanoma have also been identified in several genes, including BRAF (164757), STK11 (602216), PTEN (601728), TRRAP (603015), DCC (120470), GRIN2A (138253), ZNF831, BAP1 (603089), and RASA2 (601589). A large percentage of melanomas (40-60%) carry an activating somatic mutation in the BRAF gene, most often V600E (164757.0001) (Davies et al., 2002; Pollock et al., 2003).
Pai syndrome is characterized by mild hypertelorism, midline cleft lip, nasal and facial polyps, pericallosal lipoma, ocular anomalies, and normal neuropsychologic development (Guion-Almeida et al., 2007).
Increased size of the maxillary central secondary incisor tooth.
Abnormal largeness of the eye with an axial length > 2.5 standard deviations from population mean.
Mitral annular calcification (MAC) results from progressive calcium deposition along and beneath the mitral valve annulus.
High urine magnesium in the presence of hypomagnesemia.
A neurocutaneous syndrome with characteristics of congenital hypomelanotic and hypermelanotic cutaneous macules. It has been described in individuals spanning three generations of an Indian family. Some of the patients also had retarded growth and intellectual deficit.
Waldenstrom macroglobulinemia (WM) is a malignant B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and hypersecretion of monoclonal immunoglobulin M (IgM) protein (review by Vijay and Gertz, 2007). The importance of genetic factors is suggested by the observation of familial clustering of WM (McMaster, 2003). Whereas WM is rare, an asymptomatic elevation of monoclonal IgM protein, termed 'IgM monoclonal gammopathy of undetermined significance' (IgM MGUS) is more common. Patients with IgM MGUS can progress to develop WM, at the rate of 1.5% to 2% per year (Kyle et al., 2003). Genetic Heterogeneity of Waldenstrom Macroglobulinemia One locus for susceptibility to Waldenstrom macroglobulinemia (WM1) maps to chromosome 6p21.3. Another locus (WM2; 610430) maps to chromosome 4q.
Increased vertical dimension of the corpus callosum. This feature can be visualized by sagittal sections on magnetic resonance tomography imaging of the brain.
Psoriasis (177900) is a chronic inflammatory skin disease that may have an autoimmune basis. The disorder has a strong but complex genetic basis, with a concordance rate of 50 to 70% among monozygotic twins. Psoriatic arthritis affects more than 10% of patients with psoriasis and, in most cases, there is an association between the severity of the arthritis and the skin involvement (Gudjonsson et al., 2002).
Localized fluid retention and tissue swelling caused by a compromised lymphatic system, affecting mainly the legs.
Nails whose growth is slower than normal.
Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation is an autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes (summary by Ostergaard et al., 2012). Robitaille et al. (2014) found that MCLMR includes a broader spectrum of ocular disease, including retinal detachment with avascularity of the peripheral retina, and noted phenotypic overlap with familial exudative vitreoretinopathy (FEVR; see EVR1, 133780). Birtel et al. (2017) observed intrafamilial and intraindividual variability in retinal phenotype, and noted that syndromic manifestations in some patients are too subtle to be detected during a routine ophthalmologic evaluation. Variable expressivity and reduced penetrance have also been observed in some families (Jones et al., 2014; Li et al., 2016). Autosomal recessive forms of microcephaly with chorioretinopathy have been reported (see 251270). See also Mirhosseini-Holmes-Walton syndrome (autosomal recessive microcephaly with pigmentary retinopathy and mental retardation; 268050), which has been mapped to chromosome 8q21.3-q22.1.
Loss (reduction of previously present) of subcutaneous adipose tissue in the region of the trunk.
An abnormal increase in the amount of intramuscular fat tissue.
An abnormal increase in the amount of intraabdominal fat tissue.
A minor trait of the lip transmitted in an autosomal dominant fashion. It has been described through several generations from three families in Japan. In all cases the nodule was asymptomatic and strictly isolated.
HCV, which is principally transmitted by blood, infects about 3% of the world's population. HCV infection causes acute hepatitis, which is self-resolving in 20 to 50% of cases but does not confer permanent immunity. In 50 to 80% of cases, HCV infection becomes chronic and results in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. As a result, HCV infection is a leading killer worldwide and the most common cause of liver failure in the U.S. HCV is opportunistic in individuals infected with human immunodeficiency virus (HIV; see 609423), approximately 25% of whom are coinfected with HCV. HCV infection is also associated with cryoglobulinemia (see 123550), a B-lymphocyte proliferative disorder (Pawlotsky, 2004; Chisari (2005); Pileri et al., 1998).
Platyspondylic lethal skeletal dysplasia, Torrance type is a severe disorder of bone growth. People with this condition have very short arms and legs, underdeveloped pelvic bones, and unusually short fingers and toes (brachydactyly). This disorder is also characterized by flattened spinal bones (platyspondyly) and an exaggerated curvature of the lower back (lordosis). Infants with this condition are born with a small chest with short ribs that can restrict the growth and expansion of the lungs.As a result of these serious health problems, some affected fetuses do not survive to term. Infants born with platyspondylic lethal skeletal dysplasia, Torrance type usually die at birth or shortly thereafter from respiratory failure. A few affected people with milder signs and symptoms have lived into adulthood.
Leri pleonosteosis is an autosomal dominant skeletal disorder characterized by flexion contractures of the interphalangeal joints, limited movement of multiple joints, and short, broad metacarpals, metatarsals, and phalanges. Additional features may include chronic joint pain, short stature, bony overgrowths, spinal cord compression, scleroderma-like skin changes, and blepharophimosis. The clinical features overlap with several other musculoskeletal conditions, including Myhre syndrome (MYHRS; 139210), and geleophysic dysplasia (GPHYSD1; 231050) (summary by Banka et al., 2015).
Progressively increasing bone density of the skull base without significant changes in bony contour.
Congenital laryngeal (glottic) webs are uncommon, membrane-like structures that extend across the laryngeal lumen near the level of the vocal cords. They are thought to result from incomplete resorption of an epithelial layer that normally obliterates the developing laryngeal opening at about the sixth week of embryologic life. This layer is usually completely eliminated by the tenth week. Most laryngeal webs occur at the glottic level and affect the vocal cords. More than 90% are located anteriorly and extend toward the arytenoids. While affected persons may have onset of manifestations at any age, with hoarse or weak voice and frequent upper respiratory infections, they usually manifest the condition as infants, with respiratory distress, stridor, and an unusual cry (Strakowski et al., 1988; Singh et al., 2009).
A delay in the process of formation and maturation of the epiphysis of one or more long bones.
A two-part calcaneus, a finding that probably results from delayed coalescence of two primary calcaneal centers of ossification.
Multiple circumscribed bony excrescences located in the ribs.
A mild degree of slow or limited growth after birth, being between two and three standard deviations below age- and sex-related norms.
Multiple exostoses originating in long bones.
Absence or underdevelopment of the lacrimal gland.
Congenital nasolacrimal drainage system impatency is relatively common, occurring in approximately 20% of children within the first year of life. Such infants typically manifest persistent epiphora and/or recurrent infections of the lacrimal pathway such as conjunctivitis. The most frequent site of such obstruction occurs at the distal intranasal segment of the nasolacrimal drainage system at the valve of Hasner (summary by Wang and Cunningham, 2011). Congenital dacryocystocele, an uncommon variant of nasolacrimal duct obstruction, characterized by the appearance of a cystic blue mass over the area of the lacrimal duct soon after birth. Dacryocystoceles are thought to result from a persistent membrane at the valve of Hasner and a functional obstruction of the common canaliculus or valve of Rosenmuller. The resulting lacrimal sac distention has been reported to be more common in female and non-Hispanic white patients, and familial cases have been described only sporadically. Common presenting signs include dacryocystitis, facial cellulitis, and respiratory distress; the development of astigmatism in association with dacryocystocele has only rarely been observed (summary by Shekunov et al., 2010).
A hereditary neurological disorder with characteristics of excessive startle responses. The disease manifests shortly after birth with violent jerking to noise and touch, and massive and sustained stiffening of the trunk and limbs, clenching fists, and attacks of a high frequency trembling. Motor milestones are often mildly delayed, but intellectual development is usually normal. Mutations in the GLRA1 gene (5q32) are found in about 30% of patients. These mutations are transmitted as an autosomal dominant or recessive trait. The GLRA1 gene encodes the alpha1 subunit of the juvenile neuronal receptor for the inhibitory neurotransmitter, glycine. Mutations of this subunit cause a variety of dysfunctions of the neuronal chloride (Cl-) channel. Mutations in the GLRB, GPHN and SLC6A5 genes (4q31.3, 14q24 and 11p15.2-p15.1) have also been observed.
Hyperkeratosis affecting the palm of the hand and the sole of the foot in areas exposed to friction.
Punctate palmoplantar keratoderma type I, also called keratosis punctate palmoplantaris type Buschke-Fisher-Brauer, is a rare autosomal dominant hereditary skin disease characterized by multiple hyperkeratotic centrally indented papules that develop in early adolescence or later and are irregularly distributed on the palms and soles. In mechanically irritated areas, confluent plaques can be found. Interfamilial and intrafamilial severity shows broad variation. There have been reports of an association between PPKP and the development of early- and late-onset malignancies, including squamous cell carcinoma (summary by Giehl et al., 2012). Another form of PPKP type I has been mapped to chromosome 8q24 (PPKP1B; 614936). Other forms of punctate palmoplantar keratoderma include a porokeratotic type (PPKP2; 175860) and focal acrohyperkeratosis (PPKP3; 101850). For a general phenotypic description and a discussion of genetic heterogeneity of palmoplantar keratoderma (PPK), see epidermolytic PPK (144200).
Palmoplantar keratoderma (PPK) is a complex group of hereditary syndromes that have been classified into diffuse, punctate, and focal forms according to the pattern of hyperkeratosis on the palms and soles (Lucker et al., 1994). For a discussion of phenotypic and genetic heterogeneity of palmoplantar keratoderma, see epidermolytic PPK (144200).
Palmoplantar keratoderma with deafness is a disorder characterized by skin abnormalities and hearing loss. Affected individuals develop unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma) beginning in childhood. Hearing loss ranges from mild to profound. It begins in early childhood and gets worse over time. Affected individuals have particular trouble hearing high-pitched sounds.The signs and symptoms of this disorder may vary even within the same family, with some individuals developing only skin abnormalities and others developing only hearing loss.
Keratoconus, the most common corneal dystrophy, is a bilateral, noninflammatory progressive corneal ectasia. Clinically, the cornea becomes progressively thin and conical, resulting in myopia, irregular astigmatism, and corneal scarring. The disease usually arises in the teenage years, eventually stabilizing in the third and fourth decades. The incidence of keratoconus is 1 in 2,000 in the general population; it occurs with no ethnic or gender preponderance, and causes significant visual impairment in young adults. No specific treatment exists except to replace the corneal tissue by surgery (corneal transplantation) when visual acuity can no longer be corrected by contact lenses (summary by Dash et al., 2006). Ihalainen (1986) reviewed various conditions with which keratoconus is at times associated. Keratoconus is frequent in cases of amaurosis congenita of Leber (204000). Genetic Heterogeneity of Keratoconus Also see KTCN2 (608932), mapped to 16q22.3-q23.1; KTCN3 (608586), mapped to 3p14-q13; KTCN4 (609271), mapped to 2p24; KTCN5 (614622), mapped to 5q14.1-q21.3; KTCN6 (614623), mapped to 9q34; KTCN7 (614629), mapped to 13q32; KTCN8 (614628), mapped to 14q24; and KTCN9 (617928), caused by mutation in the TUBA3D gene (617878) on 2q21.
Increased susceptibility to bacterial infections of the skin, as manifested by recurrent episodes of infectious dermatitis.
Keratoendotheliitis fugax hereditaria is an autosomal dominant corneal disease that periodically and fleetingly affects the corneal endothelium, stroma, and vision, eventually resulting in central corneal stromal opacities in some patients. The disease is characterized by episodes of unilateral ocular pain, pericorneal injection, and photophobia. The acute symptoms vanish in 1 to 2 days, but vision remains blurry for several weeks. Onset occurs between ages 3 and 12 years, and may involve either eye. Episodes generally decrease in frequency and become more mild with age (summary by Turunen et al., 2018).
Keratitis is a rare ocular disorder presenting with congenital and progressive features predominantly involving the anterior segment of the eye. The major clinical symptoms are anterior stromal corneal opacification and vascularization of the peripheral cornea. Progression of the opacification and vascularization into the central cornea may occur with corresponding reduction in visual acuity. Other anterior segment features include variable radial defects of the iris stroma and foveal hypoplasia (summary by Mirzayans et al., 1995).
Increased distance between the maxillary central permanent incisor tooth. [HPO:ibailleulforestier]
A developmental defect leading to the union of two adjacent vertebrae.
A morphological abnormality of the vertebral arch, i.e., of the posterior part of a vertebra.
A developmental anomaly in which the kidneys are fused and localized on the same side of the midline. This anomaly is thought to result from disruption of the normal embryologic migration of the kidneys.
The presence of a fistula (abnormal tunnel) between the anal canal and the perineum.
Eyelashes that draw the attention of the viewer due to increased density and/or length and/or curl without meeting the criteria of trichomegaly.
A soft tissue prominence of the ventral aspects of the fingertips. The term ""persistent fetal fingertip pads"" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist.
Patients with mitral valve prolapse-3 (MVP3) have nonsyndromic MVP of variable severity with an autosomal dominant pattern of inheritance. For a general phenotypic description and discussion of genetic heterogeneity of mitral valve prolapse, see MVP1 (157700).
Osteoarthritis is a common disease of the joints that primarily occurs in older adults. This condition is characterized by the breakdown of cartilage, the tough but flexible tissue that covers the ends of the bones at the joints and allows smooth joint movements. One or more parts of the body can be affected, most often the hands, shoulders, spine, knees, or hips.Osteoarthritis usually develops slowly, causing pain, stiffness, and restricted movement as the condition gets worse. Areas of bone no longer cushioned by cartilage rub against each other and start to break down. Further damage is caused as the body attempts to repair and rebuild these tissues. The immune system, which plays a role in healing injuries, targets these areas, and its response leads to inflammation of the joint tissues. Abnormal growths of bone (osteophytes) and other tissue can also occur, and may be visible as enlarged joints. Enlargement of the joints of the fingers is especially noticeable.People with osteoarthritis typically experience stiffness following periods of inactivity such as upon awakening or rising from a chair; the stiffness usually improves as they move around. In some affected individuals, the condition never causes major problems. In others, severe osteoarthritis can impair mobility and the ability to perform daily tasks, affecting quality of life and increasing the risk of other health conditions such as cardiovascular disease.Osteoarthritis is most common in middle age or late adulthood, because the cartilage at the joints naturally begins to thin as people age. However, it can occur earlier in life, especially after injuries affecting the joints such as a type of knee injury called an anterior cruciate ligament (ACL) tear. People who are overweight or whose activities are particularly stressful to the joints are also at increased risk of developing osteoarthritis.
Congenital anomalies of the kidney and urinary tract (CAKUT) comprise a broad spectrum of renal and urinary tract malformations. CAKUT structural anomalies range from complete renal agenesis (the most severe), to renal hypodysplasia, multicystic kidney dysplasia, duplex renal collecting system, ureteropelvic junction obstruction (UPJO), megaureter, posterior urethral valves (PUV), and vesicoureteral reflux (VUR). Renal abnormalities are observed in close relatives of up to 10% of CAKUT patients, although these are frequently asymptomatic. The phenotype often does not follow classic mendelian inheritance: family members with the same genetic defect may have variable phenotypes, ranging from severe renal insufficiency to asymptomatic anomalies. CAKUT occurs in about 1 in 500 live births, but are severe enough to cause neonatal death in about 1 in 2,000 births. In addition, CAKUT can occur in syndromic disorders in association with other congenital anomalies, such as papillorenal syndrome (120330) (summary by Renkema et al., 2011). Genetic Heterogeneity of Congenital Anomalies of Kidney and Urinary Tract Also see CAKUT2 (143400), caused by mutation in the TBX18 gene (604613) on chromosome 6q14, and CAKUT3 (618270), caused by mutation in the NRIP1 gene (602490) on chromosome 21q.
Recurrent invasive pneumococcal disease (IPD) is defined as 2 episodes of IPD occurring at least 1 month apart, whether caused by the same or different serotypes or strains (Ku et al., 2007). Recurrent IPD occurs in at least 2% of patients in most series, making IPD the most important known risk factor for subsequent IPD.
DOLK-congenital disorder of glycosylation (DOLK-CDG, formerly known as congenital disorder of glycosylation type Im) is an inherited condition that often affects the heart but can also involve other body systems. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.Individuals with DOLK-CDG typically develop signs and symptoms of the condition during infancy or early childhood. Nearly all individuals with DOLK-CDG develop a weakened and enlarged heart (dilated cardiomyopathy). Other frequent signs and symptoms include recurrent seizures; developmental delay; poor muscle tone (hypotonia); and dry, scaly skin (ichthyosis). Less commonly, affected individuals can have distinctive facial features, kidney disease, hormonal abnormalities, or eye problems.Individuals with DOLK-CDG typically do not survive into adulthood, often because of complications related to dilated cardiomyopathy, and some do not survive past infancy.
gene, encoding the recently identified protease, matriptase. Analysis of skin samples from the patients suggests that this enzyme plays a role in epidermal desquamation.
Rupture of an intracranial aneurysm, an outpouching or sac-like widening of a cerebral artery, leads to a subarachnoid hemorrhage, a sudden-onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension, and excessive alcohol intake are associated with subarachnoid hemorrhage (summary by Krischek and Inoue, 2006). For a discussion of genetic heterogeneity of intracranial berry aneurysm, see ANIB1 (105800).
WNV is an enveloped, neurotropic, single-stranded sense RNA flavivirus that is naturally maintained in a zoonotic cycle between avian hosts and mosquito vectors. The virus was first isolated from a Ugandan woman in 1937 and subsequently emerged in Europe and, in 1999, in New York, with eventual spread throughout North America. WNV causes a spectrum of disease ranging from acute fever to lethal encephalitis. Susceptibility to WNV is increased in the elderly and in immunocompromised individuals (summary by Diamond and Klein (2006) and Glass et al. (2005)).
A type of hypoplastic anemia in which the erythrocytes have a normal cell volume (the mean corpuscular volume is within normal limits).
Intermittently increased size of the liver.
Intermittently increased size of the spleen.
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
An exceedingly rare genetic gastroenterological disease characterised by severe malabsorption diarrhoea and a lack of intestinal enteroendocrine cells. Within the first weeks of life, patients present with vomiting, dehydration and severe diarrhoea unresponsive to various nutrients and formulas and require home parenteral nutrition. The syndrome is also associated with type 1 diabetes during childhood. This phenotype is caused by loss-of-function mutations in the NEUROG3 gene, coding for neurogenin 3, a protein implicated in endocrine enteric and pancreatic cell development.
SPG30 is an autosomal recessive form of slowly progressive spastic paraplegia characterized by onset in the first or second decades of unsteady spastic gait and hyperreflexia of the lower limbs. Mildly impaired sensation and cerebellar involvement has been reported in 1 putatively affected family (summary by Erlich et al., 2011).
Cone dystrophy with supernormal rod responses (CDSRR) is characterized by onset in the first or second decade of life of very marked photophobia, myopia, reduced color vision along the red-green axis with relatively preserved tritan discrimination, and central scotomata with peripheral widespread sensitivity loss predominating in the superior visual field. Nyctalopia is a later feature of the disorder. There is often retinal pigment epithelium disturbance at the macula with a normal retinal periphery. Autofluorescence (AF) imaging shows either a perifoveal ring or a central macular area of relative increased AF (summary by Michaelides et al., 2005).
Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is characterized by clusters of nocturnal motor seizures, which are often stereotyped and brief (5 seconds to 5 minutes). They vary from simple arousals from sleep to dramatic, often bizarre hyperkinetic events with tonic or dystonic features. Affected individuals may experience aura. Retained awareness during seizures is common. A minority of individuals experience daytime seizures. Onset ranges from infancy to adulthood. About 80% of individuals develop ADNFLE in the first two decades of life; mean age of onset is ten years. Clinical neurologic examination is normal and intellect is usually preserved, but reduced intellect, psychiatric comorbidity, or cognitive deficits may occur. Within a family, the manifestations of the disorder may vary considerably. ADNFLE is lifelong but not progressive. As an individual reaches middle age, attacks may become milder and less frequent.
Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues, such as cartilage and the lining of blood vessels, which provide strength and flexibility to structures throughout the body. The signs and symptoms of SLE vary among affected individuals, and can involve many organs and systems, including the skin, joints, kidneys, lungs, central nervous system, and blood-forming (hematopoietic) system. SLE is one of a large group of conditions called autoimmune disorders that occur when the immune system attacks the body's own tissues and organs.SLE may first appear as extreme tiredness (fatigue), a vague feeling of discomfort or illness (malaise), fever, loss of appetite, and weight loss. Most affected individuals also have joint pain, typically affecting the same joints on both sides of the body, and muscle pain and weakness. Skin problems are common in SLE. A characteristic feature is a flat red rash across the cheeks and bridge of the nose, called a ""butterfly rash"" because of its shape. The rash, which generally does not hurt or itch, often appears or becomes more pronounced when exposed to sunlight. Other skin problems that may occur in SLE include calcium deposits under the skin (calcinosis), damaged blood vessels (vasculitis) in the skin, and tiny red spots called petechiae. Petechiae are caused by a shortage of cell fragments involved in clotting (platelets), which leads to bleeding under the skin. Affected individuals may also have hair loss (alopecia) and open sores (ulcerations) in the moist lining (mucosae) of the mouth, nose, or, less commonly, the genitals.About a third of people with SLE develop kidney disease (nephritis). Heart problems may also occur in SLE, including inflammation of the sac-like membrane around the heart (pericarditis) and abnormalities of the heart valves, which control blood flow in the heart. Heart disease caused by fatty buildup in the blood vessels (atherosclerosis), which is very common in the general population, is even more common in people with SLE. The inflammation characteristic of SLE can also damage the nervous system, and may result in abnormal sensation and weakness in the limbs (peripheral neuropathy); seizures; stroke; and difficulty processing, learning, and remembering information (cognitive impairment). Anxiety and depression are also common in SLE.People with SLE have episodes in which the condition gets worse (exacerbations) and other times when it gets better (remissions). Overall, SLE gradually gets worse over time, and damage to the major organs of the body can be life-threatening.
Aminoacylase-1 deficiency (ACY1D) is a rare autosomal recessive inborn error of metabolism characterized by increased urinary excretion of specific N-actyl amino acids. Most patients show neurologic abnormalities such as intellectual disability, seizures, hypotonia, and motor delay (summary by Ferri et al., 2014).
Leprosy is a disease of peripheral sensory nerves that results from infection with Mycobacterium leprae, which was first detected in Bergen, Norway, in 1873 by Dr. Armauer Hansen. It can be effectively treated with long-term multidrug therapy. In 2006, more than 250,000 new cases of leprosy were reported to the World Health Organization. Many infected individuals have self-healing indeterminate lesions. Others with initially indeterminate lesions proceed to develop leprosy that can be classified along a clinical and immunologic spectrum from paucibacillary or tuberculoid leprosy to multibacillary or lepromatous leprosy. Most patients fall somewhere between these 2 polar forms of the disease and are classified, using pathology-based criteria developed by Ridley and Jopling (1966), as borderline tuberculoid, midborderline, and borderline lepromatous. The paucibacillary form is associated with strong M. leprae-specific cell-mediated immunity (CMI), whereas the multibacillary form is notable for the lack of antigen-specific CMI. The prevalence of paucibacillary versus multibacillary leprosy varies in different populations. M. leprae cannot be cultured in vitro and grows slowly in the footpads of mice, the liver and spleen of armadillos, and in some nonhuman primates. A genetic component to leprosy susceptibility has long been suspected. While contact with a multibacillary patient increases the relative risk of acquiring disease, most new patients have no known contact with other patients. For further information, see reviews by Fitness et al. (2002), Mira (2006), Moraes et al. (2006), Scollard et al. (2006), and Alter et al. (2008).
Autosomal dominant tubulointerstitial kidney disease caused by UMOD pathogenic variants (ADTKD-UMOD) was previously known as familial juvenile hyperuricemic nephropathy type 1 (FJHN1), medullary cystic kidney disease type 2 (MCKD2), and UMOD-associated kidney disease (or uromodulin-associated kidney disease). Typical clinical findings: Urinalysis revealing minimal protein and no blood. Slowly progressive chronic kidney failure, usually first noted in the teen years and progressing to end-stage renal disease (ESRD) between the fourth and seventh decades (Age at ESRD varies among and within families.) Hyperuricemia and gout (resulting from reduced kidney excretion of uric acid) that occurs as early as the teenage years.
A situation in which phenotypic abnormalities become evident with age.
Parietal foramina-3 is a nonsyndromic developmental defect characterized by symmetrical oval holes in the parietal bone (Chen et al., 2003). For a discussion of genetic heterogeneity of parietal foramina, see 168500.
Decreased activity of the mitochondrial respiratory chain.
Facial diplegia refers to bilateral facial palsy (bilateral facial palsy is much rarer than unilateral facial palsy).
Prostate cancer is a common disease that affects men, usually in middle age or later. In this disorder, certain cells in the prostate become abnormal and multiply without control or order to form a tumor. The prostate is a gland that surrounds the male urethra and helps produce semen, the fluid that carries sperm.Early prostate cancer usually does not cause pain, and most affected men exhibit no noticeable symptoms. Men are often diagnosed as the result of health screenings, such as a blood test for a substance called prostate specific antigen (PSA) or a medical procedure called a digital rectal exam. As the tumor grows larger, signs and symptoms can include difficulty starting or stopping the flow of urine, a feeling of not being able to empty the bladder completely, blood in the urine or semen, or pain with ejaculation. However, these changes can also occur with many other genitourinary conditions. Having one or more of these symptoms does not necessarily mean that a man has prostate cancer.The severity and outcome of prostate cancer varies widely. Early-stage prostate cancer can usually be treated successfully, and some older men have prostate tumors that grow so slowly that they may never cause health problems during their lifetime, even without treatment. In other men, however, the cancer is much more aggressive; in these cases, prostate cancer can be life-threatening.Some cancerous tumors can invade surrounding tissue and spread to other parts of the body. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers. The signs and symptoms of metastatic cancer depend on where the disease has spread. If prostate cancer spreads, cancerous cells most often appear in the lymph nodes, bones, lungs, liver, or brain. Bone metastases of prostate cancer most often cause pain in the lower back, pelvis, or hips.A small percentage of all prostate cancers cluster in families. These hereditary cancers are associated with inherited gene mutations. Hereditary prostate cancers tend to develop earlier in life than non-inherited (sporadic) cases.
Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive spastic paraplegia resulting in loss of independent ambulation in the teenage years. Additional features include optic atrophy, later onset of sensorimotor peripheral neuropathy, and progressive joint contractures; cognition remains intact (summary by Melo et al., 2015).
A type of spinal dysraphism presenting as a subcutaneous fatty mass, that is, a spinal defect associated with lipomatous tissue, and covered by skin. The most usual location for lipomyelomeningocele is at the gluteal cleft.
CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma) syndrome refers to a unique constellation of clinical manifestations including microcephaly, severe neurologic impairment, psychomotor retardation, failure to thrive, and facial dysmorphism, as well as palmoplantar keratoderma and late-onset ichthyosis. Brain magnetic resonance imaging (MRI) shows various degrees of cerebral dysgenesis including absence of corpus callosum and cortical dysplasia. The syndrome has been found to be uniformly fatal between the ages of 5 and 12 years (Fuchs-Telem et al., 2011).
Difficulty to maintain correct position of the head while standing or sitting.
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Fiber splitting or branching is a common finding in human and rat skeletal muscle pathology. Fiber splitting refers to longitudinal halving of the complete fiber, while branching originates from a regenerating end of a necrotic fiber as invaginations of the sarcolemma. In fiber branching, one end of the fiber remains intact as a single entity, while the other end has several branches.
Blau syndrome is an inflammatory disorder that primarily affects the skin, joints, and eyes. Signs and symptoms begin in childhood, usually before age 4.A form of skin inflammation called granulomatous dermatitis is typically the earliest sign of Blau syndrome. This skin condition causes a persistent rash that can be scaly or involve hard lumps (nodules) that can be felt under the skin. The rash is usually found on the torso, arms, and legs.Arthritis is another common feature of Blau syndrome. In affected individuals, arthritis is characterized by inflammation of the lining of joints (the synovium). This inflammation, known as synovitis, is associated with swelling and joint pain. Synovitis usually begins in the joints of the hands, feet, wrists, and ankles. As the condition worsens, it can involve additional joints and restrict movement by decreasing the range of motion in many joints.Most people with Blau syndrome also develop uveitis, which is swelling and inflammation of the middle layer of the eye (the uvea). The uvea includes the colored portion of the eye (the iris) and related tissues that underlie the white part of the eye (the sclera). Uveitis can cause eye irritation and pain, increased sensitivity to bright light (photophobia), and blurred vision. Other structures in the eye can also become inflamed, including the outermost protective layer of the eye (the conjunctiva), the tear glands, the specialized light-sensitive tissue that lines the back of the eye (the retina), and the nerve that carries information from the eye to the brain (the optic nerve). Inflammation of any of these structures can lead to severe vision impairment or blindness.Some individuals with Blau syndrome develop kidney disease (nephritis) due to inflammation. They may also have deposits of calcium in the kidneys (nephrocalcinosis) and often develop chronic kidney failure. Inflammation of blood vessels (vasculitis) can cause scarring and tissue death in the vessels and impedes blood flow to tissues and organs.Less commonly, Blau syndrome can affect other parts of the body, including the liver, spleen, salivary gland, brain, blood vessels, lungs, and heart. Inflammation involving these organs and tissues can impair their function and cause life-threatening complications. Rarely, affected individuals have episodes of fever or high blood pressure in the blood vessels that carry blood from the heart to the lungs (pulmonary hypertension).
Goldberg-Shprintzen syndrome is an autosomal recessive multiple congenital anomaly syndrome characterized by intellectual disability, microcephaly, and dysmorphic facial features. Most patients also have Hirschsprung disease and/or gyral abnormalities of the brain, consistent with defects in migration of neural crest cells and neurons. Other features, such as megalocornea or urogenital anomalies, may also be present. Goldberg-Shprintzen syndrome has some resemblance to Mowat-Wilson syndrome (MOWS; 235730) but is genetically distinct (summary by Drevillon et al., 2013). Yomo et al. (1991) referred to this disorder as Goldberg-Shprintzen syndrome, which should not be confused with Shprintzen-Goldberg craniosynostosis syndrome (182212) or 2 other Shprintzen syndromes (192430, 182210).
A phenotypic abnormality that is present at birth.
Progressive supranuclear palsy is a brain disorder that affects movement, vision, speech, and thinking ability (cognition). The signs and symptoms of this disorder usually become apparent in mid- to late adulthood, most often in a person's 60s. Most people with progressive supranuclear palsy survive 5 to 9 years after the disease first appears, although a few affected individuals have lived for more than a decade.Loss of balance and frequent falls are the most common early signs of progressive supranuclear palsy. Affected individuals have problems with walking, including poor coordination and an unsteady, lurching gait. Other movement abnormalities develop as the disease progresses, including unusually slow movements (bradykinesia), clumsiness, and stiffness of the trunk muscles. These problems worsen with time, and most affected people ultimately require wheelchair assistance.Progressive supranuclear palsy is also characterized by abnormal eye movements, which typically develop several years after the other movement problems first appear. Restricted up-and-down eye movement (vertical gaze palsy) is a hallmark of this disease. Other eye movement problems include difficulty opening and closing the eyelids, infrequent blinking, and pulling back (retraction) of the eyelids. These abnormalities can lead to blurred vision, an increased sensitivity to light (photophobia), and a staring gaze.Additional features of progressive supranuclear palsy include slow and slurred speech (dysarthria) and trouble swallowing (dysphagia). Most affected individuals also experience changes in personality and behavior, such as a general loss of interest and enthusiasm (apathy). They develop problems with cognition, including difficulties with attention, planning, and problem solving. As the cognitive and behavioral problems worsen, affected individuals increasingly require help with personal care and other activities of daily living.
A type of dystonia that affects the midline muscles, i.e., the chest, abdominal, and back muscles.
Lack of strength of the proximal muscles that becomes progressively more severe.
Episodic bouts of involuntary movements with dystonic, choreic, ballistic movements, or a combination thereof. There is no loss of consciousness during the attacks.
An abnormally short femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Bending or curvature of a finger toward the radial side (i.e., towards the thumb). The deviation is at the metacarpal-phalangeal joint, and this finding is distinct from clinodactyly.
Aplasia or Hypoplasia affecting the metacarpal bones.
A toe that appears disproportionately short compared to the foot.
DFNB48 is an autosomal recessive form of deafness. Affected individuals have prelingual onset of severe to profound sensorineural hearing loss affecting all frequencies (summary by Riazuddin et al., 2012).
Mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) represents a distinctive combination of clinical features that includes mesoaxial osseous synostosis at a metacarpal level, reduction of one or more phalanges, hypoplasia of distal phalanges of preaxial and postaxial digits, clinodactyly of fifth fingers, and preaxial fusion of toes (Malik et al., 2014).
Fusion of the proximal and middle phalanges of the 5th finger.
Absence or underdevelopment of the big toe.
Congenital fibrosis of the extraocular muscles (CFEOM) refers to at least eight genetically defined strabismus syndromes (CFEOM1A, CFEOM1B, CFEOM2, CFEOM3A, CFEOM3B, CFEOM3C, Tukel syndrome, and CFEOM3 with polymicrogyria) characterized by congenital non-progressive ophthalmoplegia (inability to move the eyes) with or without ptosis (droopy eyelids) affecting part or all of the oculomotor nucleus and nerve (cranial nerve III) and its innervated muscles (superior, medial, and inferior recti, inferior oblique, and levator palpabrae superioris) and/or the trochlear nucleus and nerve (cranial nerve IV) and its innervated muscle (the superior oblique). In general, affected individuals have severe limitation of vertical gaze (usually upgaze) and variable limitation of horizontal gaze. Individuals with CFEOM frequently compensate for the ophthalmoplegia by maintaining abnormal head positions at rest and by moving their heads rather than their eyes to track objects. Individuals with CFEOM3A may also have intellectual disability, social disability, Kallmann syndrome, facial weakness, and vocal cord paralysis; and/or may develop a progressive sensorimotor axonal polyneuropathy. Individuals with Tukel syndrome also have postaxial oligodactyly or oligosyndactyly of the hands. Those with CFEOM3 with polymicrogyria also have microcephaly and intellectual disability.
The pathogenesis of HIV infection and the progression from infection to AIDS vary significantly between exposed individuals. Infection occurs after the virus, which has macrophage (M)- and T lymphocyte (T)-tropic strains and more than 12 subtypes, survives an array of nonspecific, nongenetic environmental and host factors.
Preeclampsia is a complication of pregnancy in which affected women develop high blood pressure (hypertension); they can also have abnormally high levels of protein in their urine (proteinuria). This condition usually occurs in the last few months of pregnancy and often requires early delivery of the infant. However, this condition can also appear shortly after giving birth (postpartum preeclampsia).Many women with mild preeclampsia do not feel ill, and the condition is often first detected through blood pressure and urine testing in their doctor's office. In addition to hypertension and proteinuria, signs and symptoms of preeclampsia can include excessive swelling (edema) of the face or hands and a weight gain of more than 3 to 5 pounds in a week due to fluid retention. Affected women may also experience headaches, dizziness, irritability, shortness of breath, a decrease in urination, upper abdominal pain, and nausea or vomiting. Vision changes may develop, including flashing lights or spots, increased sensitivity to light (photophobia), blurry vision, or temporary blindness.In many cases, symptoms of preeclampsia go away within a few days after the baby is born. In severe cases, however, preeclampsia can damage the mother's organs, such as the heart, liver, and kidneys, and can lead to life-threatening complications. Extremely high blood pressure in the mother can cause bleeding in the brain (hemorrhagic stroke). The effects of high blood pressure on the brain (hypertensive encephalopathy) may also result in seizures. If seizures occur, the condition is considered to have worsened to eclampsia, which can result in coma. About 1 in 200 women with untreated preeclampsia develop eclampsia. Eclampsia can also develop without any obvious signs of preeclampsia.Between 10 and 20 percent of women with severe preeclampsia develop another potentially life-threatening complication called HELLP syndrome. HELLP stands for hemolysis (premature red blood cell breakdown), elevated liver enzyme levels, and low platelets (cell fragments involved in blood clotting), which are the key features of this condition.Severe preeclampsia can also affect the fetus, with impairment of blood and oxygen flow leading to growth problems or stillbirth. Infants delivered early due to preeclampsia may have complications associated with prematurity, such as breathing problems caused by underdeveloped lungs.Women who have had preeclampsia have approximately twice the lifetime risk of heart disease and stroke than do women in the general population. Researchers suggest that preeclampsia, heart disease, and stroke may share common risk factors. Women who have health conditions such as obesity, hypertension, heart disease, diabetes, or kidney disease before they become pregnant have an increased risk of developing preeclampsia. Preeclampsia is most likely to occur in a woman's first pregnancy, although it can occur in subsequent pregnancies, particularly in women with other health conditions.
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of genetic heterogeneity of autism, see 209850.
SPG28 is an autosomal recessive neurodegenerative disorder characterized by early-onset, slowly progressive lower-limb spasticity resulting in walking difficulties. Some patients also have distal sensory impairment (summary by Tesson et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
A reduction in the strength of the lower limb muscles.
A rare primary bone dysplasia disorder characterised by strikingly small secondary ossification centres (mini-epiphyses) in all or only some joints, resulting in severe bone dysplasia of the proximal femoral heads. Short stature, increased lumbar lordosis, genua vara and generalised joint laxity have also been reported.
Joint hypermobility (ability of a joint to move beyond its normal range of motion) affecting many or all joints of the body.
A rare primary bone dysplasia characterised by severe early-onset dysplasia of the proximal femurs, with almost complete absence of the secondary ossification centres and abnormal development of the femoral necks (short and broad with irregular metaphyses). It is associated with gait abnormality, mild short stature, arthralgia, and joint stiffness with limited mobility of the hips and irregular acetabula, and hip and knee pain. Coxa vara and mild spinal changes are also associated.
Irregularity of the normally smooth surface of the proximal metaphysis of the femur.
Rhabdoid tumor predisposition syndrome (RTPS) is characterized by a markedly increased risk of developing rhabdoid tumors – rare and highly aggressive malignant tumors occurring predominantly in infants and children younger than age three years. Rhabdoid tumors can occur in almost any anatomic location, commonly in the central nervous system (i.e., atypical teratoid/rhabdoid tumor [AT/RT]); more than 50% occur in the cerebellum. Other common locations include extracranial extrarenal malignant rhabdoid tumors (e.g., rhabdoid tumors of the head and neck, paravertebral muscles, liver, bladder, mediastinum, retroperitoneum, pelvis, and heart) (eMRT), rhabdoid tumor of the kidney (RTK), and possibly small-cell carcinoma of the ovary (hypercalcemic type). Individuals with RTPS typically present before age 12 months with synchronous tumors that exhibit aggressive clinical behavior.
MEDNIK is a severe multisystem disorder characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma. It shows phenotypic similarities to CEDNIK (609528) (summary by Montpetit et al., 2008).
Charcot-Marie-Tooth neuropathy type 4H (CMT4H) is a demyelinating form of CMT that is characterized by early onset (usually before age 3 years; range: birth to age 10 years) and slow progression. The degree of distal muscle weakness and amyotrophy varies between affected individuals as does the presence or absence and severity of foot deformities, scoliosis, and sensory involvement. Neuropathic pain has not been reported. To date, findings in18 individuals with molecularly confirmed CMT4H from 13 families have been reported.
Limb-girdle muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) represent the mildest end of the phenotypic spectrum of muscular dystrophies collectively known as dystroglycanopathies. The limb-girdle phenotype is characterized by onset of muscular weakness apparent after ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; review by Godfrey et al., 2007). The most severe end of the phenotypic spectrum of dystroglycanopathies is represented by congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and the intermediate range of the spectrum is represented by congenital muscular dystrophy-dystroglycanopathy with or without mental retardation (type B; see MDDGB1, 613155). Genetic Heterogeneity of Limb-Girdle Muscular Dystrophy-Dystroglycanopathy (Type C) Limb-girdle muscular dystrophy due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGC2 (613158), caused by mutation in the POMT2 gene (607439); MDDGC3 (613157), caused by mutation in the POMGNT1 gene (606822); MDDGC4 (611588), caused by mutation in the FKTN gene (607440); MDDGC5 (607155), caused by mutation in the FKRP gene (606596); MDDGC7 (616052), caused by mutation in the ISPD gene (614631); MDDGC8 (618135), caused by mutation in the POMGNT2 gene (614828); MDDGC9 (613818) caused by mutation in the DAG1 gene (128239); MDDGC12 (616094), caused by mutation in the POMK gene (615247); MDDGC14 (615352) caused by mutation in the GMPPB gene (615320); and MDDGC15 (612937), caused by mutation in the DPM3 gene (605951).
The controller signal for saccadic eye movements has two components: the pulse that moves the eye rapidly from one point to the next, and the step that holds the eye in the new position. When both the pulse and the step are not the correct size, a dysmetric refixation eye movement results.
An abnormality of eye movement characterized by impaired smooth-pursuit eye movements.
The BILU syndrome comprises humoral immunodeficiency, distal limb anomalies, dysmorphic facial features, and urogenital malformations inherited in an autosomal dominant pattern. The disorder referred to as Hoffman syndrome shows many similar features, suggesting that they represent the same disorder (summary by Hugle et al., 2011).
Vasovagal syncope (VVS) is an exaggerated tendency toward the common faint caused by a sudden and profound hypotension with or without bradycardia. Several lines of evidence indicate central and peripheral abnormalities of sympathetic function. Newton et al. (2005) stated that a definitive diagnosis of VVS is made only when a patient has reproduction of symptoms in association with hypotension or bradycardia. The head up tilt (HUT) test is the investigation carried out to induce these hemodynamic changes (Parry and Kenny, 1999). This disorder may be the same as Streeten-type orthostatic hypotensive disorder (143850).
Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Patients with C10ORF2-linked adPEO may have other clinical features including proximal muscle weakness, ataxia, peripheral neuropathy, cardiomyopathy, cataracts, depression, and endocrine abnormalities (summary by Fratter et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640). PEO caused by mutations in the POLG gene (174763) are associated with more complicated phenotypes than those forms caused by mutations in the SLC25A4 (103220) or C10ORF2 genes (Lamantea et al., 2002).
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism.
Reduced strength of the distal musculature of the legs.
Progressive external ophthalmoplegia is characterized by multiple mitochondrial DNA deletions in skeletal muscle. The most common clinical features include adult onset of weakness of the external eye muscles and exercise intolerance. Both autosomal dominant and autosomal recessive inheritance can occur; autosomal recessive inheritance is usually more severe (Filosto et al., 2003; Luoma et al., 2004). PEO caused by mutations in the POLG gene are associated with more complicated phenotypes than those forms caused by mutations in the ANT1 or C10ORF2 genes (Lamantea et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640).
Autosomal recessive spinocerebellar ataxia is a neurologic disorder characterized by onset of progressive gait difficulties, eye movement abnormalities, and dysarthria in the first or second decade of life (summary by Dy et al., 2015).
An abnormality of tracking eye movements in which smooth pursuit is interrupted by an abnormally high number of saccadic movements.
Li-Fraumeni syndrome is a rare disorder that greatly increases the risk of developing several types of cancer, particularly in children and young adults.The cancers most often associated with Li-Fraumeni syndrome include breast cancer, a form of bone cancer called osteosarcoma, and cancers of soft tissues (such as muscle) called soft tissue sarcomas. Other cancers commonly seen in this syndrome include brain tumors, cancers of blood-forming tissues (leukemias), and a cancer called adrenocortical carcinoma that affects the outer layer of the adrenal glands (small hormone-producing glands on top of each kidney). Several other types of cancer also occur more frequently in people with Li-Fraumeni syndrome.A very similar condition called Li-Fraumeni-like syndrome shares many of the features of classic Li-Fraumeni syndrome. Both conditions significantly increase the chances of developing multiple cancers beginning in childhood; however, the pattern of specific cancers seen in affected family members is different.
Stuttering is a speech disorder characterized by the presence of syllable repetitions, syllable prolongations, and interruptions in the smooth flow of speech known as blocks (summary by Riaz et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of familial persistent stuttering, see 184450.
Charcot-Marie-Tooth hereditary neuropathy type 2A (CMT2A) is a classic axonal peripheral sensorimotor neuropathy characterized by earlier and more severe involvement of the lower extremities than the upper extremities, distal upper-extremity involvement as the neuropathy progresses, more prominent motor deficits than sensory deficits, and normal (>42 m/s) or only slightly decreased nerve conduction velocities (NCVs). Postural tremor is common. Most affected individuals develop symptoms in the first or second decade. It has recently been suggested that CMT2A represents more than 90% of the severe dominant CMT2 cases. However, milder late-onset cases and unusual presentations have also been described.
Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004). For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700.
Generalized seizures with sustained increase in muscle contraction lasting a few seconds to minutes.
Seizures characterized by a sudden loss or diminution of muscle tone, which may be fragmentary, confined to a segment (limb, jaw, head), or massive, leading to a slumping to the ground .
Senior-Loken syndrome is an autosomal recessive disorder with the main features of nephronophthisis (NPHP; see 256100) and Leber congenital amaurosis (LCA; see 204000).
Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder with atypical features. It is clinically heterogeneous with 3 main phenotypes: type I is an infantile-onset neuroaxonal dystrophy (609241); type II, also known as Kanzaki disease, is an adult-onset disorder characterized by angiokeratoma corporis diffusum and mild intellectual impairment; and type III is an intermediate disorder (see 609241) with mild to moderate neurologic manifestations (Desnick and Schindler, 2001).
Excretion of peptides conjugated to sialic acid in the urine.
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Increased width of the skin of vermilion border region of upper lip.
Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disorder. It is clinically heterogeneous with 3 main phenotypes: type I is an infantile-onset neuroaxonal dystrophy; type II, also known as Kanzaki disease (609242), is an adult-onset disorder characterized by angiokeratoma corporis diffusum and mild intellectual impairment; and type III is an intermediate disorder with mild to moderate neurologic manifestations (Desnick and Schindler, 2001).
Alpha-N-acetylgalactosaminidase (NAGA) deficiency type 3 is a rare clinically heterogeneous type of NAGA deficiency (see this term) with developmental, neurologic and psychiatric manifestations presenting at an intermediate age.
Griscelli syndrome is an inherited condition characterized by unusually light (hypopigmented) skin and light silvery-gray hair starting in infancy. Researchers have identified three types of this disorder, which are distinguished by their genetic cause and pattern of signs and symptoms.Griscelli syndrome type 1 involves severe problems with brain function in addition to the distinctive skin and hair coloring. Affected individuals typically have delayed development, intellectual disability, seizures, weak muscle tone (hypotonia), and eye and vision abnormalities. Another condition called Elejalde disease has many of the same signs and symptoms, and some researchers have proposed that Griscelli syndrome type 1 and Elejalde disease are actually the same disorder.People with Griscelli syndrome type 2 have immune system abnormalities in addition to having hypopigmented skin and hair. Affected individuals are prone to recurrent infections. They also develop an immune condition called hemophagocytic lymphohistiocytosis (HLH), in which the immune system produces too many activated immune cells called T-lymphocytes and macrophages (histiocytes). Overactivity of these cells can damage organs and tissues throughout the body, causing life-threatening complications if the condition is untreated. People with Griscelli syndrome type 2 do not have the neurological abnormalities of type 1.Unusually light skin and hair coloring are the only features of Griscelli syndrome type 3. People with this form of the disorder do not have neurological abnormalities or immune system problems.
Hypopigmented hair that appears silver-gray.
Reduced ability to move the femur outward to the side.
A situation in which mutation carriers do not show clinically evident phenotypic abnormalities.
An abnormal enlargement of the head, including the scalp, the cranial bone, and the contents of the cranium that is present at the time of birth; representative examples include tuberous sclerosis, neurofibromatosis, and various other genetic causes.
A congenital defect in the occipital region of the skull, covered by skin of the scalp and containing meninges or remnants of glial or neural tissues.
Progressively reduced strength of the distal musculature.
Familial isolated glucocorticoid deficiency is an adrenocortical failure characterized by very low levels of plasma cortisol despite high levels of plasma adrenocorticotropin (ACTH). Moreover, the adrenal response to ACTH is severely impaired. There is no mineralocorticoid deficiency and the renin-angiotensin system is not affected (summary by Genin et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200).
Abnormally reduced concentration of cortisol in the blood.
SPG26 is an autosomal recessive form of complicated spastic paraplegia characterized by onset in the first 2 decades of life of gait abnormalities due to lower limb spasticity and muscle weakness. Some patients have upper limb involvement. Additional features include intellectual disability, peripheral neuropathy, dysarthria, cerebellar signs, extrapyramidal signs, and cortical atrophy. The disorder is slowly progressive (summary by Boukhris et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Loeys-Dietz Syndrome with aortic aneurysm or dissection.
An abnormally increased ability of the skin to permit light to pass through (translucency) such that subcutaneous structures such as veins display an increased degree of visibility.
Abnormal tortuous (i.e., twisted) form of arteries affecting most or all arteries.
A separation of the layers within the wall of the ascending aorta. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space.
Congenital disorders of glycosylation (CDGs) are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. Different forms of CDGs can be recognized by altered isoelectric focusing (IEF) patterns of serum transferrin. For a general discussion of CDGs, see CDG Ia (212065) and CDG Ib (602579).
Autosomal recessive hypotrichosis is a condition that affects hair growth. People with this condition have sparse hair (hypotrichosis) on the scalp beginning in infancy. This hair is usually coarse, dry, and tightly curled (often described as woolly hair). Scalp hair may also be lighter in color than expected and is fragile and easily broken. Affected individuals often cannot grow hair longer than a few inches. The eyebrows, eyelashes, and other body hair may be sparse as well. Over time, the hair problems can remain stable or progress to complete scalp hair loss (alopecia) and a decrease in body hair.Rarely, people with autosomal recessive hypotrichosis have skin problems affecting areas with sparse hair, such as redness (erythema), itchiness (pruritus), or missing patches of skin (erosions) on the scalp. In areas of poor hair growth, they may also develop bumps called hyperkeratotic follicular papules that develop around hair follicles, which are specialized structures in the skin where hair growth occurs.
A multiple congenital anomalies syndrome, described in one family to date, with characteristics of branchial cysts or fistula, ear malformations, congenital hearing loss (conductive, sensorineural, and mixed), internal auditory canal hypoplasia, strabismus, trismus, abnormal fifth fingers, vitiliginous lesions, short stature and mild learning disability. Renal and urethral abnormalities are absent.
Hypoplastic/small distal phalanx of the fifth finger.
An abnormality of the middle-ear ossicles (three small bones called malleus, incus, and stapes) that are contained within the middle ear and serve to transmit sounds from the air to the fluid-filled labyrinth (cochlea).
Ichthyosis with confetti is a disorder of the skin. Individuals with this condition are born with red, scaly skin all over the body, which can be itchy in some people. In childhood or adolescence, hundreds to thousands of small patches of normal skin appear, usually on the torso. The numerous pale spots surrounded by red skin look like confetti, giving the condition its name. The patches of normal skin increase in number and size over time.In addition to red, scaly skin, people with ichthyosis with confetti typically have abnormally thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma). Many affected individuals have excess hair (hirsutism) on some parts of the body, particularly on the arms and legs. Because of their skin abnormalities, people with ichthyosis with confetti are at increased risk of developing skin infections.
Czech dysplasia is an autosomal dominant skeletal dysplasia characterized by early-onset, progressive pseudorheumatoid arthritis, platyspondyly, and short third and fourth toes (Marik et al., 2004; Kozlowski et al., 2004).
Decreased width of the wing (or ala) of the ilium (which is the large expanded portion which bounds the greater pelvis laterally).
'Familial pseudohyperkalemia' (PSHK) is a term that was coined to describe conditions in which a patient presents with pseudohyperkalemia as a result of a temperature-based abnormality in the transport of potassium (K) and sodium (Na) across the red cell membrane, in association with essentially normal hematology. PSHK can be considered to be the clinically benign, nonhemolytic cousin of hereditary stomatocytic leaky-cell, congenital hemolytic anemias (see 194380) (summary by Gore et al., 2002). For a discussion of clinical and genetic heterogeneity of the hereditary stomatocytoses, see 194380.
PCWH syndrome is a complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy (see 118200), central dysmyelination, Waardenburg syndrome, and Hirschsprung disease (see 142623) (Inoue et al., 2004). Inoue et al. (2004) proposed the acronym PCWH for this disorder.
An abnormality of the regulation of the autonomic nervous system. [HPO:probinson]
White color (lack of pigmentation) of the eyelashes.
White color (lack of pigmentation) of the eyebrow.
Lack of measurable response to stimulation of auditory evoked potentials.
Auditory neuropathy is a type of hearing loss defined by the preservation of cochlear outer hair cell function and abnormal or absent auditory brainstem responses. Auditory neuropathy may accompany peripheral neuropathy in a variety of dominant syndromes such as Charcot-Marie-Tooth disease (Satya-Murti et al., 1979) and has been observed in Friedreich ataxia (Satya-Murti et al., 1980). Auditory neuropathy unassociated with peripheral neuropathy most commonly occurs as a sporadic or recessive trait; see, for example, 601071.
A type of hearing impairment prominently characterized by a difficulty in understanding speech, rather than an inability to hear speech. Poor speech discrimination is a very common symptom of high frequency hearing loss.
Distal arthrogryposis type 4 (DA4) is distinguished by the presence of scoliosis (summary by Bamshad et al., 2009). For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Autosomal dominant limb-girdle muscular dystrophy-3 is characterized by slowly progressive proximal muscle weakness affecting the upper and lower limbs. Onset is usually in adulthood, but can occur during the teenage years. Affected individuals may also develop cataracts before age 50 (summary by Vieira et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511).
Muscular atrophy affecting proximally located muscles of the legs, i.e., of the thigh.
Individuals with high altitude adaptation hemoglobin can survive in extremely hypoxic conditions without an increase in hematocrit or the development of erythrocytosis or polycythemia vera (summary by Lorenzo et al., 2014).
Excessive bending, twisting, and winding of a cerebral artery.
Combined oxidative phosphorylation deficiency is an autosomal recessive multisystem disorder with variable manifestations resulting from a defect in the mitochondrial oxidative phosphorylation (OXPHOS) system. Onset occurs at or soon after birth, and features can include growth retardation, microcephaly, hypertonicity, axial hypotonia, encephalopathy, cardiomyopathy, and liver dysfunction. Death usually occurs in the first weeks or years of life (summary by Smits et al., 2011). Genetic Heterogeneity of Combined Oxidative Phosphorylation Deficiency See also COXPD2 (610498), caused by mutation in the MRPS16 gene (609204) on 10q22; COXPD3 (610505), caused by mutation in the TSFM gene (604723) on 12q14; COXPD4 (610678), caused by mutation in the TUFM gene (602389) on 16p11; COXPD5 (611719), caused by mutation in the MRPS22 gene (605810) on 3q23; COXPD6 (300816), caused by mutation in the AIFM1 gene (300169) on Xq26; COXPD7 (613559), caused by mutation in the C12ORF65 gene (613541) on 12q24; COXPD8 (614096), caused by mutation in the AARS2 gene (612035) on 6p21; COXPD9 (614582), caused by mutation in the MRPL3 gene (607118) on 3q22; COXPD10 (614702), caused by mutation in the MTO1 gene (614667) on 6q13; COXPD11 (614922), caused by mutation in the RMND1 gene (614917) on 6q25; COXPD12 (614924), caused by mutation in the EARS2 gene (612799) on 16p13; COXPD13 (614932), caused by mutation in the PNPT1 gene (610316) on 2p16; COXPD14 (614946), caused by mutation in the FARS2 gene (611592) on 6p25; COXPD15 (614947), caused by mutation in the MTFMT gene (611766) on 15q; COXPD16 (615395), caused by mutation in the MRPL44 gene (611849) on 2q36; COXPD17 (615440), caused by mutation in the ELAC2 gene (605367) on 17p11; COXPD18 (615578), caused by mutation in the SFXN4 gene (615564) on 10q26; COXPD19 (615595), caused by mutation in the LYRM4 gene (613311) on 6p25; COXPD20 (615917), caused by mutation in the VARS2 gene (612802) on 6p21; COXPD21 (615918), caused by mutation in the TARS2 gene (612805) on 1q21; COXPD22 (616045), caused by mutation in the ATP5A1 gene (164360) on 18q12; COXPD23 (616198), caused by mutation in the GTPBP3 (608536) gene on 19p13; COXPD24 (616239), caused by mutation in the NARS2 gene (612803) on 11q14; COXPD25 (616430), caused by mutation in the MARS2 gene (609728) on 2q33; COXPD26 (616539), caused by mutation in the TRMT5 gene (611023) on 14q23; COXPD27 (616672), caused by mutation in the CARS2 gene (612800) on 13q34; COXPD28 (616794), caused by mutation in the SLC25A26 gene (611037) on 3p14; COXPD29 (616811), caused by mutation in the TXN2 gene (609063) on 22q12; COXPD30 (616974), caused by mutation in the TRMT10C gene (615423) on 3q12; and COXPD31 (617228), caused by mutation in the MIPEP gene (602241) on 13q12; COXPD32 (617664), caused by mutation in the MRPS34 gene (611994) on 16q13; COXPD33 (617713), caused by mutation in the C1QBP gene (601269) on 17p13; and COXPD34 (617872), caused by mutation in the MRPS7 gene (611974) on 17q25; COXPD35 (617873), caused by mutation in the TRIT1 gene (617840) on 1p34; COXPD36 (617950), caused by mutation in the MRPS2 gene (611971) on 9q34; COXPD37 (618329), caused by mutation in the MICOS13 gene (616658) on 19p13; COXPD38 (618378), caused by mutation in the MRPS14 gene (611978) on 1q23; and COXPD39 (618397), caused by mutation in the GFM2 gene (606544) on 5q13.
Decreased occipito-frontal (head) circumference (OFC). For the microcephaly OFC must be between -3 SD and -2 SD compared to appropriate, age matched, normal standards (i.e. -3 SD <= OFC < -2 SD).
Salt and pepper developmental regression syndrome, also known as Amish infantile epilepsy syndrome, is an autosomal recessive neurocutaneous disorder characterized by infantile onset of refractory and recurrent seizures associated with profoundly delayed psychomotor development and/or developmental regression as well as abnormal movements and visual loss (summary by Fragaki et al., 2013). Affected individuals develop hypo- or hyperpigmented skin macules on the trunk, face, and extremities in early childhood (summary by Boccuto et al., 2014). Not all patients have overt seizures (Lee et al., 2016).
A cessation of the development of a child in the areas of motor skills, speech and language, cognitive skills, and social and/or emotional skills, following the onset of epilepsy.
Loss of developmental skills, as manifested by loss of developmental milestones. [DDD:hvfirth]
Reduced intensity of muscle tendon reflexes in the upper limbs. Reflexes are elicited by stretching the tendon of a muscle, e.g., by tapping.
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). For a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis, see CLN1 (256730).
Loss of previously present mental and motor abilities.
An intracellular accumulation of autofluorescent lipopigment storage material in a trabecular or fingerprint-like pattern.
An intracellular accumulation of autofluorescent lipopigment storage material in a curved pattern.
The presence of clear, sharply defined vacuoles in the lymphocyte cytoplasm.
Increased width of the ischium, which forms the lower and back part of the hip bone.
An alteration of the normally relatively smooth margins of the kneecap in radiographic images leading to an irregular contour.
Reduction in bone mineral density affecting any or all of the tarsal bones, seven bones of the foot comprising the calcaneus, talus, cuboid, navicular, and the cuneiform bones.
Decrease in mass and density of the metatarsal bones.
Pierson syndrome is an autosomal recessive disorder comprising congenital nephrotic syndrome with diffuse mesangial sclerosis and distinct ocular abnormalities, including microcoria and hypoplasia of the ciliary and pupillary muscles, as well as other anomalies. Many patients die early, and those who survive tend to show neurodevelopmental delay and visual loss (summary by Zenker et al., 2004). Mutations in the LAMB2 gene also cause nephrotic syndrome type 5 with or without mild ocular anomalies (NPHS5; 614199).
Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs most often in the skin, but may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes (summary by Habif, 2010). For a discussion of genetic heterogeneity of malignant melanoma, see 155600.
A large pigmented lesion measuring 5-15 mm in diameter with irregular, notched, and ill defined border and with color that may range from tan to dark brown to pink.
Posterior column ataxia with retinitis pigmentosa is an autosomal recessive neurologic disorder characterized by childhood-onset retinitis pigmentosa and later onset of gait ataxia due to sensory loss (summary by Ishiura et al., 2011).
Abnormal intestinal contractions, such as spasms and intestinal paralysis, related to the loss of the ability of the gut to coordinate muscular activity because of endogenous or exogenous causes.
Pigment migration into the retina in a bone-spicule configuration (resembling the nucleated cells within the lacuna of bone).
Emanuel syndrome is characterized by pre- and postnatal growth deficiency, microcephaly, hypotonia, severe global developmental delays, ear anomalies, preauricular tags or pits, cleft or high-arched palate, congenital heart defects, kidney abnormalities, and genital abnormalities in males.
Placement of the nipples at a lower than normal location.
A thickening of the skin thickness in the posterior aspect of the fetal neck. A nuchal fold measurement is obtained in a transverse section of the fetal head at the level of the cavum septum pellucidum and thalami, angled posteriorly to include the cerebellum. The measurement is taken from the outer edge of the occiput bone to the outer skin limit directly in the midline. A measurement 6 mm or more is considered significant between 18 and 24 weeks and a measurement of 5 mm or more is considered significant at 16 to 18 weeks (pmid:16100637).
Age-related cataracts are one of the leading causes of visual impairment and blindness among the elderly worldwide. Among age-related cataracts, cortical opacities rank as the second most common type (Iyengar et al., 2004). The preferred title/symbol of this entry was formerly 'Cataract, Age-Related Cortical, 1; ARCC1.'
A tall and slim body build with increased arm span to height ratio (>1.05) and a reduced upper-to-lower segment ratio (<0.85), i.e., unusually long arms and legs. The extremities as well as the hands and feet are unusually slim.
Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
A multiple malformation syndrome with characteristics of congenital diaphragmatic abnormalities, genital defects and cardiac malformations. Less than 15 patients have been reported worldwide. Ambiguous or female external genitalia are present in individuals with 46,XY karyotype. The genital abnormalities are variable and may include a true double vagina or septate vagina, absent uterus, abnormal male gonads in the presence of normal external female genitalia or male pseudohermaphroditism with abnormal internal female genitalia. Complex cyanotic congenital heart defects, (hypoplastic right lungs, anomalous pulmonary venous return and abnormalities of the diaphragm) are frequent. One patient with rhabdomyomatous dysplasia of the lungs has been reported. Mutations in the WT1 gene have been identified in some patients with Meacham syndrome. All patients reported to date died in early childhood.
Butterfly-shaped pigmentary macular dystrophy is an autosomal dominant eye disease characterized by bilateral accumulation of pigment in the macular area that resembles the wings of a butterfly (summary by van Lith-Verhoeven et al., 2003). For a general phenotypic description and a discussion of genetic heterogeneity of patterned macular dystrophy, see 169150.
A rare primary immunodeficiency due to a defect in adaptive immunity characterised by the absence of CD8 positive T cells with normal immunoglobulin and specific antibody titres in blood and susceptibility to recurrent respiratory bacterial and viral infections. Symptom severity ranges from fatal respiratory insufficiency to mild or asymptomatic phenotypes.
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
Spondylometaphyseal dysplasia with cone-rod dystrophy (SMDCRD) is characterized by postnatal growth deficiency resulting in profound short stature, rhizomelia with bowing of the lower extremities, platyspondyly with anterior vertebral protrusions, progressive metaphyseal irregularity and cupping with shortened tubular bones, and early-onset progressive visual impairment associated with a pigmentary maculopathy and electroretinographic evidence of cone-rod dysfunction (summary by Hoover-Fong et al., 2014). Yamamoto et al. (2014) reviewed 16 reported cases of SMDCRD, noting that all affected individuals presented uniform skeletal findings, with rhizomelia and bowed lower limbs observed in the first year of life, whereas retinal dystrophy had a more variable age of onset. There was severe disproportionate short stature, with a final height of less than 100 cm; scoliosis was usually mild. Visual loss was progressive, with stabilization in adolescence.
A bending or abnormal curvature of the tibia.
Metaphyseal cupping refers to an inward bulging of the metaphyseal profile giving the metaphysis a cup-like appearance.
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Abnormality of macular or foveal pigmentation.
An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed.
Nortriptyline is a tricyclic that can be identified by the secondary amine in its chemical structure. Tricyclics are commonly prescribed for psychological disorders and pain management. Genetic variants in cytochrome P450 2D6 (CYP2D6) may affect treatment success of nortriptyline or other tricyclics with the secondary amine functional group. Patients with poor metabolizer variants of CYP2D6 may require reductions in dose or alternative agents in order to circumvent common adverse anticholinergic, central nervous system, or cardiac effects. Guidelines regarding the use of pharmacogenomic tests in dosing for nortriptyline and other tricyclics have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Codeine, an opioid analgesic, is used for the treatment of pain. It is metabolized by cytochrome P450-2D6 (CYP2D6) to morphine, an active metabolite with pain-relief action. The CYP2D6 gene has many polymorphisms that result in different enzyme activities. An individual can be an ultra-rapid, extensive, intermediate, or poor metabolizer of codeine, based on their CYP2D6 genotype. The CYP2D6 ultra-rapid phenotype is associated with a higher risk of severe toxicity when treated with codeine, due to increased metabolism of codeine and thus enhanced morphine formation. Conversely, the CYP2D6 poor metabolizer phenotype is associated with ineffective pain relief from codeine treatment due to reduced formation of morphine. Accordingly, therapeutic recommendations for codeine based on an individual’s CYP2D6 genotype have been published by the Clinical Pharmacogenetics Implementation Consortium (CPIC) in Clinical Pharmacology and Therapeutics and are available on the PharmGKB website.
Waardenburg syndrome type 2 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (review by Read and Newton, 1997). WS type 2D is caused by mutation in the SNAI2 gene (602150). Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; 193510). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS3 (148820), and WS4 (277580).
Stomatin-deficient cryohydrocytosis with neurologic defects is an autosomal dominant disorder characterized by delayed psychomotor development, seizures, cataracts, and pseudohyperkalemia resulting from defects in the red blood cell membrane. The disorder combines the neurologic features of Glut1 deficiency syndrome-1 (GLUT1DS1; 606777), resulting from impaired glucose transport at the blood-brain barrier, and hemolytic anemia/pseudohyperkalemia with stomatocytosis, resulting from a cation leak in erythrocytes (summary by Bawazir et al., 2012). For a discussion of clinical and genetic heterogeneity of red cell stomatocyte disorders, see 194380.
Cleft palate as an isolated malformation behaves as an entity distinct from cleft lip with or without cleft palate (see 119530). Dominantly inherited cleft soft palate in 4 generations has been reported (Jenkins and Stady, 1980); see 119570.
MDDGB6 is an autosomal recessive congenital muscular dystrophy with mental retardation and structural brain abnormalities (Longman et al., 2003). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Mercuri et al., 2009). For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
The presence of calcium deposition in the cerebral white matter surrounding the cerebral ventricles.
Cerebral hemorrhage that occurs before birth.
A diverse group of congenital brain developmental disorders characterized by defects in neuronal migration in the brain during early fetal development. The neuronal migration defects result in brain abnormalities that are usually manifested with mental retardation and epilepsy.
A form of hepatic steatosis characterized by the presence of large, lipid-laden vesicles in the affected hepatocytes.
Forward prominence of the entire forehead, due to protrusion of the frontal bone. [pmid:19125436]
An abnormal accumulation of lipids in skeletal muscle.
An increase in the level of long-chain dicarboxylic acid in the urine.
Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003). For additional information and a discussion of genetic heterogeneity of restless legs syndrome, see RLS1 (102300).
Decreased intensity of the Achilles reflex (also known as the ankle jerk reflex), which can be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
The more common form of transposition of the great arteries, dextro-looped TGA, consists of complete inversion of the great vessels, so that the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the left ventricle. (In the less common type of TGA, levo-looped TGA, the ventricles are inverted instead) (Goldmuntz et al., 2002). This creates completely separate pulmonary and systemic circulatory systems, an arrangement that is incompatible with life. Patients with TGA often have atrial and/or ventricular septal defects or other types of shunting that allow some mixing between the circulations in order to support life minimally, but surgical intervention is always required.
Onset of disease at the age of between 1 and 5 years.
Pelizaeus-Merzbacher-like disease 1 (PMLD1) is a slowly progressive leukodystrophy that typically presents during the neonatal or early-infantile period with nystagmus, commonly associated with hypotonia, delayed acquisition of motor milestones, speech delay, and dysarthria. Over time the hypotonia typically evolves into spasticity that affects the ability to walk and communicate. Cerebellar signs (gait ataxia, dysmetria, intention tremor, head titubation, and dysdiadochokinesia) frequently manifest during childhood. Some individuals develop extrapyramidal movement abnormalities (choreoathetosis and dystonia). Hearing loss and optic atrophy are observed in rare cases. Motor impairments can lead to swallowing difficulty and orthopedic complications, including hip dislocation and scoliosis. Most individuals have normal cognitive skills or mild intellectual disability – which, however, can be difficult to evaluate in the context of profound motor impairment.
Sudden infant death with dysgenesis of the testes syndrome (SIDDT) is a rare condition that is fatal in the first year of life; its major features include abnormalities of the reproductive system in males, feeding difficulties, and breathing problems.Infants with SIDDT who are genetically male, with one X chromosome and one Y chromosome in each cell, have underdeveloped or abnormal testes. They may also have external genitalia that appear female or that do not look clearly male or clearly female (ambiguous genitalia). In affected infants who are genetically female, with two X chromosomes in each cell, development of the internal and external reproductive organs is normal.SIDDT is associated with abnormal development of the brain, particularly the brainstem, which is the part of the brain that is connected to the spinal cord. The brainstem regulates many basic body functions, including heart rate, breathing, eating, and sleeping. It also relays information about movement and the senses between the brain and the rest of the body. Many features of SIDDT appear to be related to brainstem malfunction, including a slow or uneven heart rate, abnormal breathing patterns, difficulty controlling body temperature, unusual tongue and eye movements, abnormal reflexes, seizures, and feeding difficulties. Affected infants also have an unusual cry that has been described as similar to the bleating of a goat, which is probably a result of abnormal nerve connections between the brain and the voicebox (larynx).The brainstem abnormalities lead to death in the first year of life, when affected infants suddenly stop breathing or their heart stops beating (cardiorespiratory arrest).
An anomaly of the rhythm or depth of breathing.
A severe delay in the achievement of motor or mental milestones in the domains of development of a child. [DDD:hvfirth]
Reduced convexity of the occiput (posterior part of skull).
The presence of a high and narrow palate.
Arm shortening because of underdevelopment of one or more bones of the upper extremity.
A chronic loss of ankle joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevent normal movement of the joints of the ankle.
In moyamoya disease, stenosis of the intracranial portion of the internal carotid artery leads to secondary establishment of intracranial compensatory anastomoses at different levels (leptomeninges, basal ganglia, and transdural) (summary by Sakurai et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of moyamoya disease, see MYMY1 (252350).
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.
Asperger syndrome is considered to be a form of childhood autism (see, e.g., 209850). The DSM-IV (American Psychiatric Association, 1994) specifies several diagnostic criteria for Asperger syndrome, which has many of the same features as autism. In general, patients with Asperger syndrome and autism exhibit qualitative impairment in social interaction, as manifest by impairment in the use of nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases. Gillberg et al. (2001) described the development of the Asperger syndrome (and high-functioning autism) Diagnostic Interview (ASDI), which they claimed has a strong validity in the diagnosis of the disorder. For a discussion of genetic heterogeneity of Asperger syndrome, see ASPG1 (608638).
SCA8 is a slowly progressive ataxia with disease onset typically occurring in adulthood. Onset ranges from age one to 73 years. The progression is typically over decades regardless of the age of onset. Common initial symptoms are scanning dysarthria with a characteristic drawn-out slowness of speech and gait instability; life span is typically not shortened. Some individuals present with nystagmus, dysmetric saccades and, rarely, ophthalmoplegia. Tendon reflex hyperreflexity and extensor plantar responses are present in some severely affected individuals. Life span is typically not shortened.
An impairment of the ability to track objects with the ocular smooth pursuit system, a class of rather slow eye movements that minimizes retinal target motion. [HPO:probinson]
Idiopathic scoliosis, an abnormality of the vertebral column in which patients develop lateral curvature of the spine of at least 10 degrees, affects approximately 2 to 3% of the worldwide population and has a heritable component (summary by Bashiardes et al., 2004). For a discussion of genetic heterogeneity of isolated scoliosis, see IS1 (181800).
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective). [pmid:19125436]
Insufficient circulating insulin-like growth factor-I.
Hypertension is abnormally high blood pressure in the arteries, which are the blood vessels that carry blood from the heart to the rest of the body. As the heart beats, it forces blood through the arteries to deliver nutrients and oxygen to the rest of the body. The strength of the blood pushing against the artery walls is blood pressure, which is measured in units called millimeters of mercury (mmHg). The top number in a blood pressure reading is the pressure when the heart pumps (systolic blood pressure), and the bottom number is the pressure between heart beats (diastolic blood pressure). In adults, a normal blood pressure measurement is about 120/80 mmHg. Blood pressure is considered high when the measurement is 130/80 mmHg or greater.Hypertension usually has no symptoms, and many affected individuals do not know they have the condition. However, hypertension is a major risk factor for heart disease, stroke, kidney failure, and eye problems. When blood pressure is elevated, the heart and arteries have to work harder than normal to pump blood through the body. The extra work thickens the muscles of the heart and arteries and hardens or damages artery walls. As a result, the flow of blood and oxygen to the heart and other organs is reduced. Damage to the heart caused by the extra work and a lack of oxygen causes heart disease. In addition, damage to the arteries increases the risk of blood clots that block the flow of blood to the heart, causing a heart attack, or to the brain, causing a type of stroke known as an ischemic stroke. Another type of stroke, called a hemorrhagic stroke, can occur when a weakened blood vessel in the brain bursts. Damage to blood vessels in the kidneys impairs their ability to filter waste and remove fluid, leading to kidney failure. Problems with blood flow in the arteries of the eyes can lead to vision loss.In rare cases, dangerously high blood pressure can cause severe headaches, confusion, shortness of breath, chest pain, or nosebleeds.In about 95 percent of cases, the cause of hypertension is unknown. These cases are classified as essential hypertension. When hypertension results from an underlying condition, such as blood vessel defects that reduce blood flow; kidney disorders, which alter the amount of fluids and salts in the body; or problems with hormone-producing glands called the adrenal glands or the thyroid gland, it is classified as secondary hypertension. Hypertension is a key feature of some rare genetic disorders, including familial hyperaldosteronism, pseudohypoaldosteronism type 2, Liddle syndrome, Bartter syndrome, Gitelman syndrome, and tumors known as paragangliomas.
Flattening of the superior part of the acetabulum, which is a cup-shaped cavity at the base of the hipbone into which the ball-shaped head of the femur fits. The acetabular roof thereby appears horizontal rather than arched, as it normally does.
Autosomal recessive primary microcephaly-5 (MCPH5) is characterized by decreased occipitofrontal circumference (OFC), usually less than 3 standard deviations (SD) of the mean, present at birth and associated with mental retardation and speech delay. Other features may include short stature or mild seizures. MCPH5 is associated with a simplification of the cerebral cortical gyral pattern in some cases, which is considered within the phenotypic spectrum of primary microcephaly (review by Woods et al., 2005; Saadi et al., 2009; Passemard et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly (MCPH), see MCPH1 (251200).
A reduced level of the complement component C3 in circulation.
A complete loss of the ability to perceive vibration.
Reduced ability to perceive painful stimuli.
Fusion of the labia minora as a result of labial adhesions resulting in vaginal obstruction.
Spinocerebellar ataxia type 20 (SCA20) is characterized by a slowly progressive ataxia and dysarthria. Approximately two thirds of those affected also display palatal tremor (""myoclonus"") and/or abnormal phonation clinically resembling spasmodic adductor dysphonia. Dysarthria, which may be abrupt in onset, precedes the onset of ataxia in about two thirds of affected individuals, sometimes by a number of years. Hypermetric horizontal saccades (without nystagmus or disturbance of vestibulo-ocular reflex gain) are seen in about half of affected persons. Although minor pyramidal signs (brisk knee jerks, crossed adductor spread) may be seen, spasticity and extensor plantar responses are not. Cognition is normal. Clinical information is based on the findings in 16 personally examined affected members of a single Australian family of Anglo-Celtic descent.
An increased tendency to fractures following trauma, with fractures occurring without pain.
Ulceration and osteomyelitis of the distal parts of the limbs associated with necrosis and spontaneous detachment of digits or parts of digits. [HPO:probinson]
DFNB32 is characterized by prelingual progressive moderate to profound sensorineural deafness. Some affected men are infertile, and semen analysis has shown high percentages of immotile sperm with abnormal morphology (Imtiaz et al., 2018).
Decreased concentration of homovanillic acid (HVA) in the cerebrospinal fluid. HVA is a metabolite of dopamine.
Asperger syndrome is considered to be a form of childhood autism (see, e.g., 209850). The DSM-IV (American Psychiatric Association, 1994) specifies several diagnostic criteria for Asperger syndrome, which has many of the same features as autism. In general, patients with Asperger syndrome and autism exhibit qualitative impairment in social interaction, as manifest by impairment in the use of nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases. Gillberg et al. (2001) described the development of the Asperger syndrome (and high-functioning autism) Diagnostic Interview (ASDI), which they claimed has a strong validity in the diagnosis of the disorder. Genetic Heterogeneity of Susceptibility to Asperger Syndrome ASPG1 maps to chromosome 3q. Other autosomal loci include ASPG2 (608631) on chromosome 17p, ASPG3 (608781) on 1q21-q22, and ASPG4 (609954) on 3p24-p21. Two X-linked forms, ASPGX1 (300494) and ASPGX2 (300497), are associated with mutation in the NLGN3 gene (300336) and the NLGN4 gene (300427), respectively.
A very rare bone disorder with clinical characteristics of short stature of prenatal onset; dislocation of the knees, hips or elbows; club feet; limitation of range of motion of large joints; progressive kyphosis and occasional scoliosis. In a few patients, minor heart valve dysplasia has also been described. Intellect, vision and hearing are normal.
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
A progressive form of decreased height of the intervertebral disk.
A condition in which the helix is folded over to a greater degree than normal. That is, excessive curling of the helix edge, whereby the free edge is parallel to the plane of the ear.
Increased thickness of the helix of the ear.
Regional increase in the width (height) of the lateral eyebrow.
Hypertension is a significant risk factor for cardiac and renal disease, arteriosclerosis, retinopathy, and stroke. Systolic hypertension reflects an increase in the force of cardiac contraction, whereas diastolic hypertension reflects an increase in peripheral vascular resistance. Normalization of blood pressure is associated with reductions in morbidity and mortality related to end-organ damage.
Mandibuloacral dysplasia is a condition that causes a variety of abnormalities involving bone development, skin coloring (pigmentation), and fat distribution. People with this condition may grow slowly after birth. Most affected individuals are born with an underdeveloped lower jaw bone (mandible) and small collar bones (clavicles), leading to the characteristic features of a small chin and sloped shoulders. Other bone problems include loss of bone from the tips of the fingers (acroosteolysis), which causes bulbous finger tips; delayed closure of certain skull bones; and joint deformities (contractures).People with mandibuloacral dysplasia can have mottled or patchy skin pigmentation or other skin abnormalities. Some people with this condition have features of premature aging (a condition called progeria), such as thin skin, loss of teeth, loss of hair, and a beaked nose. Some individuals with mandibuloacral dysplasia have metabolic problems, such as diabetes.A common feature of mandibuloacral dysplasia is a lack of fatty tissue under the skin (lipodystrophy) in certain regions of the body. The two types of this disorder, mandibuloacral dysplasia with type A lipodystrophy (MADA) and mandibuloacral dysplasia with type B lipodystrophy (MADB) are distinguished by the pattern of fat distribution throughout the body. Type A is described as partial lipodystrophy; affected individuals have a loss of fatty tissue from the torso and limbs, but it may build up around the neck and shoulders. Type B is a generalized lipodystrophy, with loss of fatty tissue in the face, torso, and limbs.MADA usually begins in adulthood, although children can be affected. MADB begins earlier, often just after birth. Many babies with MADB are born prematurely.
Progressive bone resorption in the distal part of the clavicle.
Reduced amount of adipose tissue in the region of the neck.
Loss (disappearance) of previously present subcutaneous fat tissue in arm or leg.
Loss of normal subcutaneous fat tissue in the face.
The presence of an abnormally increased amount of subcutaneous adipose tissue in the trunk of the body.
A condition in which superficial veins (i.e., veins just under the skin) are more conspicuous or noticable than normal.
Abnormally prominent umbilicus (belly button).
An abnormally reduced amount of adipose tissue in the thoracic cavity.
A decreased concentration of leptin in the blood.
Autosomal dominant Charcot-Marie-Tooth disease type 2G (CMT2G) is a form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy. CMT2G [has only been described in 1 familly and] onset is associated to development of foot deformity and walking difficulties between the 1st and the 8th decades, with a median range in the 2nd one. Weakness and sensory loss involve primarily the legs and ankles tendon reflexes are reduced. CMT2G has a slowly progressive course.
Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis (Laitinen et al., 2001; Illig and Wjst, 2002). For a general phenotypic description and a discussion of genetic heterogeneity of asthma, see 600807.
Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
Burn-McKeown syndrome (BMKS) is characterized by typical craniofacial features (bilateral choanal atresia/stenosis, short palpebral fissures, coloboma of the lower eyelids, prominent nasal bridge and widely spaced eyes, and large and protruding ears), congenital heart defects, and short stature. Intellect is usually normal. To date, the diagnosis of BMKS has been molecularly confirmed in 14 individuals from 11 families.
A rare developmental defect during embryogenesis with characteristics of unilateral or bilateral, partial or full-thickness, variably sized defect of the inferior eyelid (ranging from a small notch to complete absence of the entire lid) which is usually triangular in shape (with base at eyelid margin) and located on the lateral third of the lid. It can occur isolated, associated with facial clefting or as part of a syndrome.
Underdevelopment of the ulna on only one side.
Bilateral clubfoot deformity (see HP:0001762).
Syndactyly with fusion of toes four and five.
The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors, in which case it is considered to be a congenital disorder (Benson et al., 2003). Genetic Heterogeneity of Sick Sinus Syndrome Sick sinus syndrome-2 (SSS2; 163800) is caused by mutation in the HCN4 gene (605206). Susceptibility to sick sinus syndrome (SSS3; 614090) is influenced by variation in the MYH6 gene (160710).
Legionnaire disease (LD) is a type of pneumonia caused by Legionella pneumophila, a flagellated gram-negative bacterium found primarily in warm water environments. The disease and the bacterium were discovered following an outbreak traced to a 1976 American Legion convention in Philadelphia. A number of risk factors for acquiring LD have been identified, including age, smoking, chronic lung disease, cancer, and immunosuppression (summary by Hawn et al., 2003).
Early-onset neurodegeneration in the human retina can lead to Leber congenital amaurosis (LCA), the most severe human form of inherited photoreceptor-neuron degeneration resulting in congenital blindness, with an incidence of approximately 1 in 80,000 (summary by Koenekoop et al., 2012). NMNAT1 (608700) mutations consistently cause severe and rapidly progressive macular degeneration leading to severe central atrophy with an appearance of congenital macular coloboma in the neonatal period, as well as an unusual early-onset atrophy of the optic nerve (Perrault et al., 2012).
Intracranial berry aneurysms are saccular outpouchings of the intracranial arteries, most commonly at arterial bifurcations, characterized by arterial wall remodeling. Most cases of ruptured intracranial berry aneurysms result in a subarachnoid hemorrhage, associated with high morbidity and mortality (summary by van der Voet et al., 2004). For a discussion of genetic heterogeneity of intracranial berry aneurysm, see ANIB1 (105800).
Abnormal transferrin isoform profile consistent with a type I congenital disorder of glycosylation. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II.
Familial erythrocytosis-2 is an autosomal recessive disorder characterized by increased red blood cell mass, increased serum levels of erythropoietin (EPO; 133170), and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events (Cario, 2005). Familial erythrocytosis-2 has features of both primary and secondary erythrocytosis. In addition to increased circulating levels of EPO, consistent with a secondary, extrinsic process, erythroid progenitors are also hypersensitive to EPO, consistent with a primary, intrinsic process (Prchal, 2005).
Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004). For a discussion of genetic heterogeneity of susceptibility to myopia, see (160700).
MUTYH-associated polyposis (MAP), caused by biallelic pathogenic variants in MUTYH, is characterized by a greatly increased lifetime risk of colorectal cancer (CRC) (43% to almost 100% in the absence of timely surveillance). Although typically associated with ten to a few hundred colonic adenomatous polyps that are evident at a mean age of about 50 years, colonic cancer develops in some individuals with biallelic MUTYH pathogenic variants in the absence of polyposis. Duodenal adenomas are found in 17%-25% of individuals with MAP. Serrated adenomas, hyperplastic/sessile serrated polyps, and mixed (hyperplastic and adenomatous) polyps can also occur. The lifetime risk of duodenal cancer is about 4%. Also noted are a modestly increased risk for rather late-onset malignancies of the ovary, bladder, and skin, and some evidence for an increased risk for breast and endometrial cancer. Some affected individuals develop sebaceous gland tumors and more recently, thyroid abnormalities (multinodular goiter, single nodules, and papillary thyroid cancer) have been reported.
Auras with sensations of buzzing, drumming sounds or single tones.
Monogenic diabetes caused by inactivating mutation(s) in the gene HNF1A, encoding hepatocyte nuclear factor 1-alpha.
Belongs to the heterogeneous family of metabolic myopathies. It is characterised by progressive exercise intolerance manifesting in childhood, onset of sideroblastic anaemia around adolescence, lactic acidaemia and mitochondrial myopathy. Less than 10 cases have been described so far. A 656C-->T mutation in the nuclear pseudouridine synthase 1 gene (PUS1), localised to 12q24.33, has recently been identified in some patients. Deficient pseudouridylation of mitochondrial tRNAs may be responsible for the oxidative phosphorylation disorder. Transmission is autosomal recessive.
Generalized (unlocalized) atrophy affecting muscles of the limbs in both proximal and distal locations.
A rare form of localised hypertrichosis characterised by hair growth near the laryngeal prominence during childhood. This isolated anomaly has been described in around 20 individuals. Transmission may be autosomal recessive or dominant with variable penetrance.
The Verloes-David-Pfeiffer mesomelia-synostoses syndrome is an autosomal dominant form of mesomelic dysplasia comprising typical acral synostoses combined with ptosis, hypertelorism, palatal abnormality, congenital heart disease, and ureteral anomalies (summary by Isidor et al., 2009). Mesomelia and synostoses are also cardinal features of the Kantaputra type of mesomelic dysplasia (156232).
Telangiectases in the area of the nails.
CODAS is an acronym for cerebral, ocular, dental, auricular, and skeletal anomalies. CODAS syndrome is a rare disorder characterized by a distinctive constellation of features that includes developmental delay, craniofacial anomalies, cataracts, ptosis, median nasal groove, delayed tooth eruption, hearing loss, short stature, delayed epiphyseal ossification, metaphyseal hip dysplasia, and vertebral coronal clefts (summary by Strauss et al., 2015).
A shift from the normally round (convex) appearance of the iliac wing towards a square-like appearance.
An extremely rare variant of aplasia cutis congenita with characteristics of congenital absence of skin on the upper and/or lower limbs. These lesions usually heal spontaneously resulting in a hypotrichotic scar. May be associated with junctional epidermolysis bullosa. There have been no further descriptions in the literature since 1980.
Udd distal myopathy is characterized by weakness of ankle dorsiflexion and inability to walk on the heels after age 35 years. Disease progression is slow and muscle weakness remains confined to the anterior tibial muscles. The long toe extensors become clinically involved after ten to 20 years, leading to foot drop and clumsiness when walking. In the mildest form, Udd distal myopathy can remain unnoticed even in the elderly.
A rare syndrome with features of multiple congenital anomalies with macrocephaly (of post-natal onset), large anterior fontanelle, progressive complex spastic paraplegia, coarse facial features (broad and high forehead, deeply set eyes, short philtrum with thin upper lip, large mouth and prominent incisors), seizures, and intellectual deficit of varying severity. Inheritance appears to be autosomal recessive.
The primitive reflexes are a group of behavioural motor responses which are found in normal early development, are subsequently inhibited, but may be released from inhibition by cerebral, usually frontal, damage. They are thus part of a broader group of reflexes which reflect release phenomena, such as exaggerated stretch reflexes and extensor plantars. They do however involve more complex motor responses than such simple stretch reflexes, and are often a normal feature in the neonate or infant.
A tendency or compulsion to examine objects by mouth.
Disease with characteristics of early-onset severe polycystic kidney disease with various manifestations of tuberous sclerosis (multiple angiomyolipomas, lymphangioleiomyomatosis and periventricular calcifications of the central nervous system). A contiguous gene syndrome caused by a large deletion involving both the PKD1 and TSC2 genes (16p13.3). Transmission is autosomal dominant.
A very rare syndrome with the association of thin and short upper and lower tarsus and absence of the lower eyelashes. It has been described in 11 patients from a four-generation family. There is no other unusual feature. Inheritance is autosomal dominant.
Syndrome that is characterised by the association of epibulbar dermoids and aplasia cutis congenital.
Helicobacter pylori is a microaerophilic, gram-negative bacterium that colonizes the gastric mucosa of approximately 50% of the world's population, and is a primary pathogenic factor in benign and malignant gastroduodenal disease (Warren and Marshall, 1983; Blaser and Parsonnet, 1994). Tomb et al. (1997) reported the complete sequence of the circular genome of H. pylori. The 1,667,867-bp genome contains 1,590 predicted coding sequences (genes). Sequence analysis of these genes indicated that the organism has systems for motility, for scavenging iron, and for DNA restriction and modification. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.
Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (the endometrium). People with Lynch syndrome may occasionally have noncancerous (benign) growths (polyps) in the colon, called colon polyps. In individuals with this disorder, colon polyps occur earlier but not in greater numbers than they do in the general population.
Oblique facial clefts are a rare form of orofacial clefting, comprising about 0.25% of all facial clefts. Two major types have been described classically: nasoocular and oroocular, the latter of which can be subdivided into oromedial-canthal and orolateral-canthal (summary by Dasouki et al., 1988).
Hereditary palmoplantar keratoderma is characterized by hyperkeratosis of the skin of palms and soles. Lind et al. (1994) described an autosomal dominant form of diffuse nonepidermolytic PPK, designated PPK type Bothnia, which has a high prevalence of 0.3 to 0.55% in the 2 northernmost provinces of Sweden, situated to the west and the northwest of the Gulf of Bothnia. The Bothnian form is frequently complicated by fungal infections and lacks the histopathologic features distinctive of epidermolytic PPK (144200). For discussion of phenotypic and genetic heterogeneity of palmoplantar keratoderma (PPK), see epidermolytic PPK (144200).
The condition multiple cutaneous and mucosal venous malformations (VMCM) is characterized by the presence of small, multifocal bluish cutaneous and/or mucosal venous malformations. They are usually present at birth. New lesions appear with time. Small lesions are usually asymptomatic; larger lesions can invade subcutaneous muscle and cause pain. Malignant transformation has not been reported.
An inherited non-syndromic congenital ichthyosis characterised by the infancy-onset of palmoplantar peeling of the skin (aggravated by exposure to water and by occlusion) associated with dry, scaly skin over most of the body. Pruritus and hypohidrosis may also be associated. Well-demarcated areas of denuded skin appear in moist and traumatised regions and skin biopsies reveal reduced cell-cell adhesion in the basal and suprabasal layers, prominent intercellular oedema, numerous aggregates of keratin filaments in basal keratinocytes, attenuated cornified cell envelopes, and epidermal barrier impairment.
Waardenburg syndrome type II (WS2) is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (Hughes et al., 1994). WS type 2B (WS2B) maps to chromosome 1p. Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; 193510). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS3 (148820), and WS4 (277580).
This autosomal recessive neurodevelopmental disorder is characterized by pachygyria, mental retardation, seizures, and diffuse localization of arachnoid cysts. It most likely represents a neuronal migration disorder within the lissencephaly spectrum (summary by Guzel et al., 2007).
Autosomal dominant nanophthalmos is characterized by a small eye, as indicated by short axial length, high hyperopia, high lens/eye volume ratio, and a high incidence of angle-closure glaucoma (summary by Othman et al., 1998). Genetic Heterogeneity of Nanophthalmos Nanophthalmos-1 (NNO1) has been mapped to chromosome 11p. Nanophthalmos-2 (NNO2; 609549) is caused by mutation in the MFRP gene (606227) on chromosome 11q23. Nanophthalmos-3 (NNO3; 611897) has been mapped to chromosome 2q11-q14. Nanophthalmos-4 (NNO4; 615972) is caused by mutation in the TMEM98 gene (615949) on chromosome 17q11.
Melanoma-pancreatic cancer syndrome is an inherited cancer predisposition syndrome in which mutation carriers have an increased risk of developing malignant melanoma and/or pancreatic cancer. Mutation carriers within families may develop either or both types of cancer (summary by Harinck et al., 2012). For background and phenotypic information on malignant melanoma and pancreatic cancer, see 155600 and 260350, respectively.
This syndrome has characteristics of pterygium colli, digital anomalies and craniofacial abnormalities. Digital anomalies include abnormal small thumbs, widened interphalangeal joints, and broad terminal phalanges. Craniofacial abnormalities include brachycephaly, epicanthic folds, angulated eyebrows, upward slanting of the palpebral fissures, ptosis, hypertelorism, prominent low-set and posteriorly rotated ears. It has been described in a woman and her son, but the manifestations were much less severe in the mother. The son also had intellectual deficit. The inheritance is either X-linked dominant or autosomal dominant.
Sacral defect with anterior meningocele (SDAM) is a form of caudal dysgenesis. It is present at birth and becomes symptomatic later in life, usually because of obstructive labor in females, chronic constipation, or meningitis. Inheritance is autosomal dominant (Chatkupt et al., 1994). Welch and Aterman (1984) gave a population frequency of 0.14%. Caudal dysgenesis syndrome and caudal regression syndrome are broad terms that refer to a heterogeneous constellation of congenital caudal anomalies affecting the caudal spine and spinal cord, the hindgut, the urogenital system, and the lower limbs. Approximately 15 to 25% of mothers of children with caudal dysgenesis have insulin-dependent diabetes mellitus (222100) (Lynch et al., 2000). See also Currarino syndrome (176450), a similar disorder caused by mutation in the HLXB9 gene (142994) on chromosome 7q36. Currarino syndrome classically comprises the triad of hemisacrum, anorectal malformation, and presacral mass. However, Currarino syndrome also shows phenotypic variability: Lynch et al. (2000) stated that there is variable expressivity of clinical features and that some patients with Currarino syndrome are asymptomatic. Kochling et al. (2001) found the complete triad of Currarino syndrome in only 8 of 23 patients with mutations in the HLXB9 gene, These reports suggest that some patients previously reported as having forms of sacral agenesis, including SDAM, may have had Currarino syndrome and vice versa. See also spina bifida (182940), which can be seen in some patients with sacral agenesis or caudal regression syndrome and may be etiologically related.
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment patterns observed most often in CLN8 comprise mixed combinations of 'granular,' 'curvilinear,' and 'fingerprint' profiles (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
The neuronal ceroid lipofuscinoses (NCL, or CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally (summary by Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by early-onset changes in the deep white matter of the brain observed on MRI and associated neurologic findings. The most frequent initial symptom is gait disturbance from spasticity beginning between ages 20 and 30 years. Twenty-three percent of affected individuals have stroke-like episodes before age 40 years. Mood changes (apathy and irritability), pseudobulbar palsy, and cognitive dysfunction begin between ages 20 and 50 years. The disease progresses slowly over the five to 20 years following the onset of neurologic symptoms. Scalp alopecia before age 30 years and acute mid- to lower-back pain (lumbago) with onset between ages ten and 40 years are characteristic.
Pseudobulbar signs result from injury to an upper motor neuron lesion to the corticobulbar pathways in the pyramidal tract. Patients have difficulty chewing, swallowing and demonstrate slurred speech (often initial presentation) as well as abnormal behavioral symptoms such as inappropriate emotional outbursts of uncontrolled laughter or weeping etc.
Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by a progressive degeneration of photoreceptors, eventually resulting in severe visual impairment. For a discussion of genetic heterogeneity of RP, see 268000.
Childhood absence epilepsy (CAE, ECA), a subtype of idiopathic generalized epilepsy (EIG; 600669), is characterized by a sudden and brief impairment of consciousness that is accompanied by a generalized, synchronous, bilateral, 2.5- to 4-Hz spike and slow-wave discharge (SWD) on EEG. Seizure onset occurs between 3 and 8 years of age and seizures generally occur multiple times per day. About 70% of patients experience spontaneous remission of seizures, often around adolescence. There are no structural neuropathologic findings in patients with ECA (Crunelli and Leresche, 2002). Genetic Heterogeneity of Susceptibility to Childhood Absence Epilepsy The ECA1 locus has been mapped to chromosome 8q24; see also EIG1 (see 600669), which also maps to 8q24. Susceptibility to the development of childhood absence epilepsy may be conferred by variation in several genes: ECA2 (607681), conferred by variation in the GABRG2 gene (137164) on chromosome 5q31.1; ECA4 (611136), conferred by variation in the GABRA1 gene (137160) on chromosome 5q34; ECA5 (612269), conferred by variation in the GABRB3 gene (137192) on chromosome 15q12; and ECA6 (see 611942), conferred by variation in the CACNA1H gene (607904) on chromosome 16p13. See EIG11 (607628) for discussion of a locus previously designated ECA3 on chromosome 3q26.
Rhizomelic chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized by disproportionately short stature primarily affecting the proximal parts of the extremities, a typical facial appearance including a broad nasal bridge, epicanthus, high-arched palate, dysplastic external ears, and micrognathia, congenital contractures, characteristic ocular involvement, dwarfism, and severe mental retardation with spasticity. Biochemically, plasmalogen synthesis and phytanic acid alpha-oxidation are defective. Most patients die in the first decade of life. RCDP1 is the most frequent form of RCDP (summary by Wanders and Waterham, 2005). Whereas RCDP1 is a peroxisomal biogenesis disorder (PBD), RCDP3 is classified as a single peroxisome enzyme deficiency (Waterham and Ebberink, 2012). For a discussion of genetic heterogeneity of rhizomelic chondrodysplasia punctata, see 215100.
A severe form of developmental verbal apraxia with characteristics of a deficit in spontaneous speech, writing, grammatical judgment and repetition, defective articulation, moderate to severe degree of dyspraxia, a reduced use of consonant clusters and comprehension delay. Hearing and intelligence are normal. Inheritance is autosomal dominant with full penetrance.
Stargardt macular degeneration is a genetic eye disorder that causes progressive vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, Stargardt macular degeneration affects a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. In most people with Stargardt macular degeneration, a fatty yellow pigment (lipofuscin) builds up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. In addition to central vision loss, people with Stargardt macular degeneration have problems with night vision that can make it difficult to navigate in low light. Some affected individuals also have impaired color vision. The signs and symptoms of Stargardt macular degeneration typically appear in late childhood to early adulthood and worsen over time.
The distal limb deficiencies-micrognathia syndrome is characterized by the combination of symmetric severe distal limb reduction deficiencies affecting all four limbs (oligodactyly), microretrognathia, and microstomia with or without cleft palate.
An extremely rare disorder of sex development, reported in only two siblings to date. The syndrome has clinical features of 46,XY complete gonadal dysgenesis in association with severe dwarfism with generalised chondrodysplasia (bell-shaped thorax, micromelia, brachydactyly). Other reported features in the live sibling included eye anomalies, dysmorphic features, muscular hypoplasia, mild intellectual deficiency and severe microcephaly with cerebellar vermis hypoplasia. An autosomal recessive inheritance has been suggested.
An autosomal recessive form of rickets caused by inactivating mutation(s) in the CYP2R1 gene, encoding vitamin D 25-hydroxylase, the hepatic enzyme that converts vitamin D to 25-hydroxyvitamin D, the precursor of 1,25-dihydroxyvitamin D (calcitriol). The condition is characterized by reduced serum concentrations of 25-hydroxyvitamin D, hypophosphatemia, hypocalcemia with secondary hyperparathyroidism and elevated serum alkaline phosphatase, and by failure to thrive, seizures, muscle weakness, and rickets.
Irregularity of the normally smooth surface of the metaphyses.
Bladder exstrophy and epispadias complex (BEEC) is an anterior midline defect with variable expression involving the infraumbilical abdominal wall including the pelvis, urinary tract, and external genitalia (Gearhart and Jeffs, 1998). BEEC is one of the most severe urologic birth defects because of its profound impact on continence, sexual function, and morbidity due to the effect of chronic and recurrent infections on renal function. The term 'exstrophy,' derived from the Greek work ekstriphein, which literally means 'turn inside out,' was first used by Chaussier in 1780. Martinez-Frias et al. (2001) emphasized that exstrophy of the cloaca and exstrophy of the bladder are 2 different expressions of a primary developmental field defect. Cloacal exstrophy is a feature of the OEIS (omphalocele-exstrophy-imperforate anus-spinal defects) complex (258040). Exstrophy of the cloaca includes the persistence and exstrophy of a common cloaca that receives ureters, ileum, and a rudimentary hindgut and is associated with failure of fusion of the genital tubercles and pubic rami, incomplete development of the lumbosacral vertebrae with spinal dysraphism, imperforate anus, cryptorchidism and epispadias in males and anomalies of the mullerian duct derivatives in females, and a wide range of urinary tract anomalies. Omphalocele is common, and most patients have a single umbilical artery.
A rare familial skeletal dysplasia with characteristics of multiple epiphyseal dysplasia with extremely retarded ossification. It has been described in 6 members of a unique consanguineous family. A mutation in PTHR1 gene is responsible for this syndrome. Transmission is autosomal recessive.
Mitochondrial nonsyndromic hearing loss and deafness is characterized by sensorineural hearing loss (SNHL) of variable onset and severity. Pathogenic variants in MT-RNR1 can be associated with predisposition to aminoglycoside ototoxicity and/or late-onset SNHL. Hearing loss associated with aminoglycoside ototoxicity is bilateral and severe to profound, occurring within a few days to weeks after administration of any amount (even a single dose) of an aminoglycoside antibiotic such as gentamycin, tobramycin, amikacin, kanamycin, or streptomycin. Pathogenic variants in MT-TS1 are usually associated with childhood onset of SNHL that is generally nonsyndromic – although the MT-TS1 substitution m.7445A>G has been found in some families who also have palmoplantar keratoderma (scaling, hyperkeratosis, and honeycomb appearance of the skin of the palms, soles, and heels).
A lack of strength of the proximal muscles.
Recurring episodes of myoglobinuria, i.e., of the presence of myoglobin in the urine. This is usually a consequence of rhabdomyolysis, i.e., of the destruction of muscle tissue.
Paroxysmal, recurrent episodes of vomiting.
Descreased amplitude of eletrical response upon electroretinography.
Reduced strength of the orbicularis oculi, the circumorbital muscle in the face that closes the eyelid.
A functional anomaly of the upper motor neuron. The upper motor neurons are neurons of the primary motor cortex which project to the brainstem and spinal chord via the corticonuclear, corticobulbar and corticospinal (pyramidal) tracts. They are involved in control of voluntary movements.nDysfunction leads to weakness, impairment of fine motor movements, spasticity, hyperreflexia and abnormal pyramidal signs. [HPO:probinson]
Y chromosome infertility is characterized by azoospermia (absence of sperm), severe oligozoospermia (<1 x 106 sperm/mL semen), moderate oligozoospermia (1-5 x 106 sperm/mL semen), or mild oligozoospermia (5-20 x 106 sperm/mL semen). Males with Y chromosome infertility usually have no obvious symptoms, although physical examination may reveal small testes.
Berg and Bearn (1966, 1966) discovered an X-linked serum protein type by means of heteroantiserum made specific by absorption. Since the group-specific antigen appears to be located in the alpha-2-macroglobulin of serum, the name Xm was assigned to the system. The distribution of phenotypes in families and in populations was consistent with X-linkage.
Syndrome with characteristics of short stature, trigonocephaly and developmental delay. It has been described in three males. Moderate intellectual deficit was reported in one of the males and the other two patients displayed psychomotor retardation. X-linked transmission has been suggested but autosomal recessive inheritance cannot be ruled out.
Individuals with X-linked dystonia-parkinsonism (XDP) have dystonia of varying severity and parkinsonism. XDP afflicts primarily Filipino men and, rarely, women. The mean age of onset in men is 39 years; the clinical course is highly variable with parkinsonism as the initial presenting sign, overshadowed by dystonia as the disease progresses. Features of parkinsonism include resting tremor, bradykinesia, rigidity, postural instability, and severe shuffling gait. The dystonia develops focally, most commonly in the jaw, neck, trunk, and eyes, and less commonly in the limbs, tongue, pharynx, and larynx, the most characteristic being jaw dystonia often progressing to neck dystonia. Individuals with pure parkinsonism have non-disabling symptoms that are only slowly progressive; those who develop a combination of parkinsonism and dystonia can develop multifocal or generalized symptoms within a few years and die prematurely from pneumonia or intercurrent infections. Female carriers are mostly asymptomatic, though a small minority may manifest dystonia, parkinsonism, or chorea.
Inherited thyroxine-binding globulin deficiency is a genetic condition that typically does not cause any health problems.Thyroxine-binding globulin is a protein that carries hormones made or used by the thyroid gland, which is a butterfly-shaped tissue in the lower neck. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Most of the time, these hormones circulate in the bloodstream attached to thyroxine-binding globulin and similar proteins. If there is a shortage (deficiency) of thyroxine-binding globulin, the amount of circulating thyroid hormones is reduced.Researchers have identified two forms of inherited thyroxine-binding globulin deficiency: the complete form (TBG-CD), which results in a total loss of thyroxine-binding globulin, and the partial form (TBG-PD), which reduces the amount of this protein or alters its structure. Neither of these conditions causes any problems with thyroid function. They are usually identified during routine blood tests that measure thyroid hormones.Although inherited thyroxine-binding globulin deficiency does not cause any health problems, it can be mistaken for more serious thyroid disorders (such as hypothyroidism). Therefore, it is important to diagnose inherited thyroxine-binding globulin deficiency to avoid unnecessary treatments.
GATA1-related cytopenia is characterized by thrombocytopenia and/or anemia ranging from mild to severe. One or more of the following may also be present: platelet dysfunction, mild ß-thalassemia, neutropenia, and congenital erythropoietic porphyria (CEP) in males. Thrombocytopenia typically presents in infancy as a bleeding disorder with easy bruising and mucosal bleeding (e.g., epistaxis). Anemia ranges from minimal (mild dyserythropoiesis) to severe (hydrops fetalis requiring in utero transfusion). At the extreme end of the clinical spectrum, severe hemorrhage and/or erythrocyte transfusion dependence are life long; at the milder end, anemia and the risk for bleeding may decrease spontaneously with age. Heterozygous females may have mild to moderate symptoms such as menorrhagia.
Reduced platelet count that occurs sporadically, i.e., it comes and goes.
Underdevelopment of the proximal epiphysis of the femur.
Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals (Elliott and Evans, 2006). For additional phenotypic information and a discussion of genetic heterogeneity of split-hand/split-foot malformation, see SHFM1 (183600).
Spinal and bulbar muscular atrophy (SBMA) is a gradually progressive neuromuscular disorder in which degeneration of lower motor neurons results in muscle weakness, muscle atrophy, and fasciculations. SBMA occurs only in males. Affected individuals often show gynecomastia, testicular atrophy, and reduced fertility as a result of mild androgen insensitivity.
A cleft of the lip with overlying mucous membrane.
A decreased proportion of circulating CD4-positive helper T cells relative to total T cell count.
A decreased proportion of circulating CD8-positive, alpha-beta T cells relative to total number of T cells.
Syndrome with manifestations of syndactyly of the fingers and toes, characteristic facies (startled facial expression with a small pointed nose, micrognathia, long dark eyelashes and prominent eyebrows) and intellectual deficit. Less than 10 cases have been described in the literature so far. Abnormal dermatoglyphic patterns, growth retardation and brachycephaly have also been reported. Transmission appears to be autosomal or X-linked recessive.
Syndrome with the association of skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, psychomotor retardation and facial abnormalities. So far, it has been described in two males (maternal first cousins). The mode of inheritance was suggested to be X-linked recessive.
Early infantile epileptic encephalopathy-2 is an X-linked dominant severe neurologic disorder characterized by onset of seizures in the first months of life and severe global developmental delay resulting in mental retardation and poor motor control. Other features include lack of speech development, subtle dysmorphic facial features, sleep disturbances, gastrointestinal problems, and stereotypic hand movements. There is some phenotypic overlap with Rett syndrome (312750), but EIEE2 is considered to be a distinct entity (summary by Fehr et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
An abnormality of the T wave on the electrocardiogram, which mainly represents the repolarization of the ventricles.
Degenerative changes of the peripheral retina consisting of close-packed tiny cystic spaces at the outer plexiform/inner nuclear retinal level. The degeneration is very common in adult eyes and starts adjacent to the ora serrata and extends circumferentially and posteriorly.
A reduction of previously attained ability to see. [HPO:probinson]
Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in children. Most cases are caused by mutation in the E1-alpha subunit gene on the X chromosome. X-linked PDH deficiency is one of the few X-linked diseases in which a high proportion of heterozygous females manifest severe symptoms. The clinical spectrum of PDH deficiency is broad, ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis (Robinson et al., 1987; Brown et al., 1994). Genetic Heterogeneity of Pyruvate Dehydrogenase Complex Deficiency PDH deficiency can also be caused by mutation in other subunits of the PDH complex, including a form (PDHXD; 245349) caused by mutation in the component X gene (PDHX; 608769) on chromosome 11p13; a form (PDHBD; 614111) caused by mutation in the PDHB gene (179060) on chromosome 3p14; a form (PDHDD; 245348) caused by mutation in the DLAT gene (608770) on chromosome 11q23; a form (PDHPD; 608782) caused by mutation in the PDP1 gene (605993) on chromosome 8q22; and a form (PDHLD; 614462) caused by mutation in the LIAS gene (607031) on chromosome 4p14.
Properdin (factor P) is a plasma protein that is active in the alternative complement pathway of the innate immune system. It is a positive regulatory factor that binds to many microbial surfaces to stabilize the C3b,Bb convertase. Deficiency of properdin is associated in particular with a heightened susceptibility to Neisseria species (Janeway et al., 2001).
An abnormality of the functioning of any aspect of the alternative complement pathway.
A rare developmental defect during embryogenesis syndrome with characteristics of Robin sequence (micrognathia, glossoptosis, cleft palate), atrial septal defect, persistence of the left superior vena cava and talipes equinovarus. The phenotype is variable, some patients present with further dysmorphic characteristics (e.g. hypertelorism, ear abnormalities) while others do not have any key findings. Additional features, such as syndactyly, polydactyly, or brain anomalies (e.g. cerebellar hypoplasia), have also been reported. The syndrome is almost invariably lethal with affected males either dying prenatally or living just a few months. There is evidence this syndrome is caused by mutation in the RBM10 gene on chromosome Xp11.23.
A decreased concentration of citrulline in the blood.
An increased concentration of glutamine in the blood.
A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.
X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5), part of the spectrum of PRPS1-related disorders, is characterized by peripheral neuropathy, early-onset (prelingual) bilateral profound sensorineural hearing loss, and optic neuropathy. The onset of peripheral neuropathy is between ages five and 12 years. The lower extremities are affected earlier and more severely than upper extremities. Initial manifestations often include foot drop or gait disturbance. Onset of visual impairment is between ages seven and 20 years. Intellect and life span are normal. Carrier females do not have findings of CMTX5.
A rare form of hereditary optic atrophy seen in only 4 families to date. With onset in early childhood the disease has characteristics of progressive loss of visual acuity, significant optic nerve pallor and occasionally additional neurological manifestations, with females being unaffected.
FRMD7-related infantile nystagmus (FIN) is characterized by either the onset of horizontal, conjugate, gaze-dependent nystagmus in the first six months of life or periodic alternating nystagmus (with cyclical changes of nystagmus direction) of infantile onset. Binocular vision and color vision are normal and visual acuity is typically better than 6/12. An abnormal head posture is seen in approximately 15% of affected individuals. The eyes are structurally normal and electrophysiologic studies (e.g., visual evoked potential, electroretinogram) are normal. Affected females report slightly better visual acuity than affected males; however, no differences between males and females in the amplitude, frequency, and waveform of nystagmus are observed.
A proximal renal tubular disorder resulting in diminished reabsorption of phosphate, glucose, amino acids, urate, and low molecular weight proteins.
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Excretion in urine of proteins of a size smaller than albumin (molecular weight 69 kD).
Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004). For a discussion of genetic heterogeneity of myopia, see 160700.
X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive skeletal muscle disorder characterized by childhood onset of progressive muscle weakness and atrophy primarily affecting the proximal muscles. While onset is usually in childhood, it can range from infancy to adulthood. Many patients lose ambulation and become wheelchair-bound. Other organ systems, including the heart, are clinically unaffected. Muscle biopsy shows intracytoplasmic autophagic vacuoles with sarcolemmal features and a multilayered basal membrane (summary by Ramachandran et al., 2013; Kurashige et al., 2013, and Ruggieri et al., 2015). Danon disease (300257), caused by mutation in the LAMP2 gene (309060) on chromosome Xq24, is a distinct disorder with similar pathologic features.
A severe degree of muscular hypotonia characterized by markedly reduced muscle tone.
Enlargement of the muscles of the calf due to their replacement by connective tissue or fat.
This syndrome combines skeletal anomalies (short stature, ridging of the metopic suture, fusion of cervical vertebrae, thoracic hemivertebrae, scoliosis, sacral hypoplasia and short middle phalanges) and mild intellectual deficit. It has been described in four male cousins in three sibships. Glucose intolerance was present in three cases, and imperforated anus in one case. Carrier females had minor manifestations (fusion of cervical vertebrae and glucose intolerance). Transmission seems to be X-linked.
Mental retardation syndrome with facial abnormalities, subcortical cerebral atrophy, defective tooth development, skin dimples at the lower back, lower limb defects, clinodactyly, luxation of the patella, and eye abnormalities.
X-linked mental retardation, Miles-Carpenter type is characterised by severe intellectual deficit, microcephaly, exotropia and low digital arches.
Wilson-Turner syndrome is an X-linked recessive neurologic disorder characterized by intellectual disability, dysmorphic facial features, hypogonadism, short stature, and truncal obesity. Females are unaffected (Wilson et al., 1991).
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective). [HPO:curators, pmid:19125428]
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base. [pmid:19125428]
The presence of a folate sensitive fragile site at chromosome Xq28.
Accentuated, prominent philtral ridges giving rise to an exaggerated groove in the midline between the nasal base and upper vermillion border.
Distance from nasion to subnasale more than two standard deviations above the mean, or alternatively, an apparently increased length from the nasal root to the nasal base.
Increased inferior-superior length of the neck.
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Excessive amount of hair growth on forehead.
A type of cardiomyopathy characterized anatomically by deep trabeculations in the ventricular wall, which define recesses communicating with the main ventricular chamber.
Bipolar disorder is a mental health condition that causes extreme shifts in mood, energy, and behavior. This disorder most often appears in late adolescence or early adulthood, although symptoms can begin at any time of life.People with bipolar disorder experience both dramatic ""highs,"" called manic episodes, and ""lows,"" called depressive episodes. These episodes can last from hours to weeks, and many people have no symptoms between episodes. Manic episodes are characterized by increased energy and activity, irritability, restlessness, an inability to sleep, and reckless behavior. Depressive episodes are marked by low energy and activity, a feeling of hopelessness, and an inability to perform everyday tasks. People with bipolar disorder often have repeated thoughts of death and suicide, and they have a much greater risk of dying by suicide than the general population.Manic and depressive episodes can include psychotic symptoms, such as false perceptions (hallucinations) or strongly held false beliefs (delusions). Mixed episodes, which have features of manic and depressive episodes at the same time, also occur in some affected individuals.Bipolar disorder often occurs with other mental health conditions, including anxiety disorders (such as panic attacks), behavioral disorders (such as attention-deficit hyperactivity disorder), and substance abuse.
An elevation of alpha-feto protein measured in the amniotic fluid.
A bent (flexed) finger or toe joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Abnormally increased concentration of hydrogencarbonate in the urine.
Low molecular weight proteinuria with hypercalciuria and nephrocalcinosis is a form of X-linked hypercalciuric nephrocalcinosis, a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrocalcinosis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009.
Kallmann syndrome is a condition characterized by delayed or absent puberty and an impaired sense of smell.This disorder is a form of hypogonadotropic hypogonadism, which is a condition resulting from a lack of production of certain hormones that direct sexual development. These hormones are normally made in a part of the brain called the hypothalamus. Males born with hypogonadotropic hypogonadism often have an unusually small penis (micropenis) and undescended testes (cryptorchidism). At puberty, most affected individuals do not develop secondary sex characteristics, such as the growth of facial hair and deepening of the voice in males, the start of monthly periods (menstruation) and breast development in females, and a growth spurt in both sexes. Without treatment, most affected men and women are unable to have biological children (infertile).In Kallmann syndrome, the sense of smell is either diminished (hyposmia) or completely absent (anosmia). This feature distinguishes Kallmann syndrome from most other forms of hypogonadotropic hypogonadism, which do not affect the sense of smell. Many people with Kallmann syndrome are not aware that they are unable to detect odors until the impairment is discovered through testing.Kallmann syndrome can have a wide variety of additional signs and symptoms. These include a failure of one kidney to develop (unilateral renal agenesis), abnormalities of bones in the fingers or toes, a cleft lip with or without an opening in the roof of the mouth (a cleft palate), abnormal eye movements, hearing loss, and abnormalities of tooth development. Some affected individuals have a feature called bimanual synkinesis, in which the movements of one hand are mirrored by the other hand. Bimanual synkinesis can make it difficult to do tasks that require the hands to move separately, such as playing a musical instrument.
The presence of multiple impacted teeth.
Reduced ability of the natural killer cell to function in the adaptive immune response.
An abnormally increased level of immunoglobulin M in blood.
The IFAP/BRESHECK syndrome is an X-linked multiple congenital anomaly disorder with variable severity. The classic triad, which defines IFAP, is ichthyosis follicularis, atrichia, and photophobia. Some patients have additional features, including mental retardation, brain anomalies, Hirschsprung disease, corneal opacifications, kidney dysplasia, cryptorchidism, cleft palate, and skeletal malformations, particularly of the vertebrae, which constitutes BRESHECK syndrome (summary by Naiki et al., 2012).
Intrauterine growth retardation that is at least 2 standard deviations (SD) below average, but not as low as 3 SD, corrected for sex and gestational age.
A very rare benign bone dysplasia affecting skeletal structures of the lower limb and the pelvis. Less than 50 patients have been reported worldwide. The main clinical features include patellar aplasia or hypoplasia, associated with absent, delayed or irregular ossification of the ischiopubic junctions and/or the infra-acetabular axe-cut notches. Additional features found in the majority of reported patients include femur and foot anomalies. Craniofacial anomalies have been reported occasionally. Inherited in an autosomal dominant manner and is caused by mutations in the human TBX4 gene (chromosome 17q22). TBX4 mutations account for familial cases with a distinctive facial appearance and those without facial features.
Underdevelopment of the lesser trochanter.
A widely spaced gap between the first toe (the great toe) and the second toe.
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Underdevelopment of the pectoralis major.
An abnormal limitation of the mobility of the wrist.
The presence of a single, median maxillary incisor, affecting both the primary maxillary incisor and the permanent maxillary incisor.
Abnormal narrowing (stenosis) of the midnasal cavity, i.e., of the middle nasal meatus, which in neonates can cause respiratory distress.
This syndrome has features of ichthyosis, prominent full cheeks and sparse lateral eyebrows. It has been described in several individuals from four generations of one family. Transmission is autosomal dominant.
Leber congenital amaurosis comprises a group of early-onset childhood retinal dystrophies characterized by vision loss, nystagmus, and severe retinal dysfunction. Patients usually present at birth with profound vision loss and pendular nystagmus. Electroretinogram (ERG) responses are usually nonrecordable. Other clinical findings may include high hypermetropia, photodysphoria, oculodigital sign, keratoconus, cataracts, and a variable appearance to the fundus (summary by Chung and Traboulsi, 2009). For a general description and a discussion of genetic heterogeneity of LCA, see 204000.
Anton-Lamprecht (1978) stated that 4 genetic disorders of keratinization were known to have a structural defect of tonofibrils. (1) In the harlequin fetus (242500), an abnormal x-ray diffraction pattern of the horn material points to a cross-beta-protein structure instead of the normal alpha-protein structure of keratin. (2) Bullous ichthyosiform erythroderma (EHK; 113800) is characterized by an early formation of clumps and perinuclear shells due to an abnormal arrangement of tonofibrils. (3) In the Curth-Macklin form of ichthyosis hystrix, concentric unbroken shells of abnormal tonofilaments form around the nucleus. (4) In ichthyosis hystrix gravior (146600), only rudimentary tonofilaments are found with compensatory production of mucous granules.
Hypotrichosis simplex can affect all body hair or be limited to the scalp. Usually patients with the scalp-limited form of hypotrichosis present with normal hair at birth; they experience a progressive, gradual loss of scalp hair beginning at the middle of the first decade and leading to almost complete loss of scalp hair by the third decade. A few sparse, fine, short hairs remain in some individuals. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. Light and electron microscopy of hairs from early hypotrichosis simplex revealed no structural changes, whereas hairs from patients with advanced hypotrichosis showed focal areas of defective cuticular structure. Men and women are equally affected (summary by Betz et al., 2000). For a discussion of genetic heterogeneity of nonsyndromic hypotrichosis, see 605389.
A rare congenital abnormality in the laryngo-tracheal wall. It results from the incomplete development of the tracheoesophageal septum. Signs and symptoms include coughing, cyanosis, repeated pulmonary infections, and failure to gain weight.
Excess skin around the neck, often lying in horizontal folds.
Hypophosphastasia characterized by the premature loss of deciduous teeth, but without accompanying bony abnormalities.
A condition characterized by hypoparathyroidism, sensorineural deafness, and renal failure. It is related to autosomal dominant inactivating mutation(s) in GATA3, encoding a transcription factor important for the embryonic development of the parathyroid gland, the auditory stem, and the kidneys.
Hypoparathyroidism associated with homozygous mutation(s) in the PTH gene, which encodes parathyroid hormone, or in the GCM2 gene, which encodes chorion-specific transcription factor GCMb.
Hypertrichosis is defined as hair growth that is excessive for a particular site of the body or age of the patient and that is not hormone-dependent (summary by Fantauzzo et al., 2012). Genetic Heterogeneity of Congenital Generalized Hypertrichosis HTC1 has been mapped to chromosome 8q. HTC2 (307150) is caused by palindrome-mediated interchromosomal insertion at chromosome Xq27. HTC3 (135400), which can occur with or without associated gingival hyperplasia, is caused by deletion or duplication at chromosome 17q24 or by mutation in the ABCA5 gene (612503) on chromosome 17q24. Also see lanugo-like generalized congenital hypertrichosis (145700).
A rare genetic non-dystrophic myopathy with characteristics of the triad of congenital myopathy, dysmorphic features and susceptibility to malignant hyperthermia. Patients present with a wide phenotypic range, including delayed motor development, muscle weakness and fatigability, ptosis and myopathic facies (with or without creatine kinase elevations), skeletal abnormalities (short stature, scoliosis, kyphosis, lumbar lordosis and pectus carinatum/excavatum), mild dysmorphic facial features (hypertelorism, down-slanting palpebral fissures, epicanthic folds, low set ears, micrognathia), webbing of the neck, cryptorchidism, and a susceptibility to malignant hyperthermia and/or rhabdomyolysis due to intensive physical strain, viral infection or statin use.
Abnormal increase in systolic blood pressure.
Abnormal increase in diastolic blood pressure.
An abnormal increase in the average blood pressure in an individual during a single cardiac cycle.
Underdevelopment of the vermis of cerebellum.
If the two laminae of the septum pellucidum are not fused then a fluid-filled space or cavum is present. The cavum septum pellucidum is present at birth but usually obliterates by the age of 3 to 6 months. It is up to 1cm in width and the walls are parallel. It is an enclosed space and is not part of the ventricular system or connected with the subarachnoid space.
Pseudohypoaldosteronism type II (PHAII) is characterized by hyperkalemia despite normal glomerular filtration rate (GFR) and frequently by hypertension. Other associated findings in both children and adults include hyperchloremia, metabolic acidosis, and suppressed plasma renin levels. Aldosterone levels are variable, but are relatively low given the degree of hyperkalemia (elevated serum potassium is a potent stimulus for aldosterone secretion). Hypercalciuria is well described.
Patches of hyperpigmentation in the skin, which are present at birth or in early infancy and increase in size and number with age. A rare autosomal dominant disorder.
A disordered proliferation of mature tissues that are native to the kidneys.
Hyperostosis cranialis interna is a bone disorder characterized by endosteal hyperostosis and osteosclerosis of the calvaria and the skull base. The progressive bone overgrowth causes entrapment and dysfunction of cranial nerves I, II, V, VII, and VIII (Waterval et al., 2010).
Abnormal thickening of the cortex of long bones.
Increase in bone denisty in the diaphyseal (shaft) region of a metacarpal bone.
Osteosclerosis of the endosteal surface of the diaphyses (shafts) of the metatarsal bones.
Isolated hyperchlorhidrosis is an autosomal recessive condition in which excessive salt wasting in sweat can result in severe infantile hyponatremic dehydration and hyperkalemia (summary by Muhammad et al., 2011).
Congenital anomalies of the kidneys and urinary tract (CAKUT) encompasses a spectrum of developmental disorders of the urinary tract that can range from mild vesicoureteral reflux to severe renal agenesis. Other phenotypes include renal duplication, small kidneys, ureteropelvic junction obstruction, hydronephrosis, and renal dysplasia. These abnormalities can result in kidney damage, and possibly renal failure (summary by Vivante et al., 2015). For a discussion of genetic heterogeneity of CAKUT, see 610805.
A form of vitreoretinopathy characterized by thinning (erosion) of the retinal pigment epithelium that permits increased visualization of the choroidal vessels.
A mild form of myopia with up to -3.00 diopters. [ORCID:0000-0003-0986-4123]
Atrophy (loss or wasting) of the retinal pigment epithelium observed on fundoscopy or fundus imaging.
Horner syndrome, resulting from unilateral paralysis of the cervical sympathetics, comprises the classic triad of unilateral ptosis, unilateral miosis with anisocoria, and ipsilateral facial anhidrosis. Iris heterochromia may also be present (Takanashi et al., 2003).
An abnormality affecting the carpal bones of the wrist (scaphoid, lunate, triquetral, pisiform, trapezium, trapezoid, capitate, hamate).
Abacavir is a nucleoside reverse transcriptase inhibitor indicated for the treatment of HIV infection, in combination with other medications, as part of highly active antiretroviral therapy. Although abacavir is generally well tolerated, ~5–8% of patients experience a hypersensitivity reaction (HSR) during the first 6 weeks of treatment. Suspicion of an HSR requires immediate discontinuation of abacavir. Drug re-challenge is contraindicated because immediate life-threatening reactions can occur. HLA-B is a member of the major histocompatibility complex gene family and patients with at least one HLA-B*57:01 allele may develop HSR when treated with abacavir. HLA-B allele status has no effect on abacavir pharmacodynamics or pharmacokinetics; it only influences the likelihood that an HSR will occur. Guidelines regarding the use of pharmacogenomic tests in dosing for abacavir have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Acne inversa is a chronic relapsing inflammatory skin disease characterized by recurrent draining sinuses and abscesses, predominantly in skin folds that carry terminal hairs and apocrine glands. Healing occurs with substantial scarring (summary by Jansen et al., 2001). Jansen et al. (2001) provided a detailed history and review of the disorder. Genetic Heterogeneity of Familial Acne Inversa Familial acne inversa-2 with or without Dowling-Degos disease (ACNINV2; 613736) is caused by mutation in the PSENEN gene (607632) on chromosome 19q13, and familial acne inversa-3 (ACNINV3; 613737) is caused by mutation in the PSEN1 gene (104311) on chromosome 14q24.
Beukes hip dysplasia is characterized by severe progressive degenerative osteoarthritis of the hip joint in early adulthood, with underlying dysplasia confined to that region. Affected individuals are of normal stature and have no associated health problems. Symptoms of hip joint discomfort usually develop in infancy or later childhood, but may present as late as the fourth decade. Phenotypic expression is age-related and variable in severity; penetrance is incomplete and has been estimated to be 80%. The earliest primary radiographic features of BHD include bilateral shortening and broadening of the femoral neck, delayed appearance of the secondary ossification center, coxa vara, displacement of the femoral head in the acetabulum, and overgrowth of the greater trochanters. After onset of symptoms, the characteristic signs of osteoarthritis develop, including bone sclerosis, cyst formation, and narrowing of the joint space, with rapid deterioration of the joint (summary by Watson et al., 2015).
Fetal hemoglobin (HbF) levels vary considerably in healthy normal adults. The distribution of HbF and F cells, erythrocytes that contain measurable HbF, in healthy adults is continuous, although most adults have HbF of less than 0.6% of total Hb. Approximately 10 to 15% of individuals have increases of HbF ranging from 0.8% to 5%, a trait often referred to as hereditary persistence of fetal hemoglobin (HPFH), usually distributed unevenly among red cells. When coinherited with beta-thalassemia (see 613985) or sickle cell anemia (603903), HPFH can increase HbF output to levels that are clinically beneficial (Thein et al., 2007). For a general phenotypic description and a discussion of loci that may affect fetal hemoglobin levels, see HBFQTL1 (141749).
More than 2 billion people have been infected with the hepatitis B virus (HBV; see 610424), and more than 350 million of these people are chronic carriers. Each year more than half a million die as a result of acute or chronic HBV infection. Vaccination has been highly successful at preventing new HBV infections and has been implemented into the national immunization programs of more than 150 countries. However, the immune response to HBV vaccination varies greatly among individuals, with 5 to 10% of healthy adults failing to produce protective levels of antibodies. Several factors have been implicated in determining the response to HBV vaccination, including physical factors, such as age, gender, obesity, immunosuppression, and smoking, as well as variation in genes of the immune system (summary by Davila et al., 2010).
Methemoglobinemia, beta-globin type is a condition that affects the function of red blood cells. Specifically, it alters a molecule called hemoglobin within these cells. Hemoglobin within red blood cells attaches (binds) to oxygen molecules in the lungs, which it carries through the bloodstream, then releases in tissues throughout the body. Instead of normal hemoglobin, people with methemoglobinemia, beta-globin type have an abnormal form called methemoglobin, which is unable to efficiently deliver oxygen to the body's tissues. In methemoglobinemia, beta-globin type, the abnormal hemoglobin gives the blood a brown color. It also causes a bluish appearance of the skin, lips, and nails (cyanosis), which usually first appears around the age of 6 months. The signs and symptoms of methemoglobinemia, beta-globin type are generally limited to cyanosis, which does not cause any health problems. However, in rare cases, severe methemoglobinemia, beta-globin type can cause headaches, weakness, and fatigue.
Classic hereditary persistence of fetal hemoglobin (HPFH) is characterized by a substantial elevation of fetal hemoglobin (HbF) in adult red blood cells. There are no other phenotypic or hematologic manifestations. Expression of the HBG1 and HBG2 genes, which encode the gamma isoforms of HbF, is normally suppressed shortly before birth and replaced by expression of the beta- (HBB; 141900) or delta- (HBD; 142000) chains, which form adult hemoglobin. Adults normally have less than 1% HbF, whereas heterozygotes for HPFH have 5 to 30% HbF. HPFH heterozygotes have essentially normal red cell indices and a rather homogeneous distribution of HbF among red cells, termed 'pancellular.' Homozygotes for HPFH can express HbF in up to 100% of red blood cells (Thein and Craig, 1998). Delta-beta thalassemia is a hemoglobin disorder characterized by decreased or absent synthesis of the delta- and beta-globin chains with a compensatory increase in expression of fetal gamma-chain synthesis from the affected chromosome. Individuals with delta-beta thalassemia have hypochromic, microcytic anemia and increased HbF, which may mitigate the anemia depending on the level of HbF. Delta-beta thalassemia and some forms of HPFH result from deletions within the beta-globin gene cluster on chromosome 11p15; this has been referred to as 'deletional' HPFH. HPFH can also result from point mutations in the promoter regions of the gamma globulin genes HBG1 and HBG2; this has been referred to as 'non-deletional' HPFH (Ottolenghi et al., 1982; Forget, 1998). Forget (1998) noted that HPFH and delta-beta thalassemia are not clearly distinct disorders, but rather show partially overlapping features that may defy classification. Higher expression of HbF is often termed 'pancellular,' whereas lower expression of HbF is often termed 'heterocellular,' although these represent a spectrum. Approximately 10% of the population has HPFH manifest as modest elevations of HbF (1 to 4%) present in a subset of red cells (about 4.5%) termed F cells. This is also sometimes referred to as 'heterocellular' HPFH, and is considered to be a multifactorial trait influenced by multiple genetic loci (Thein and Craig, 1998).
Hemifacial spasm is usually diagnosed in persons in their mid-forties. It often begins with involuntary clonic contractions or twitching of the orbicularis oculi muscle and progresses to involve the entire musculature innervated by the facial nerve (summary by Coad et al., 1991 and Miwa et al., 2002).
A malformation syndrome involving the abnormal growth of the facial skeleton as well as its soft tissue structure and organs. The syndrome has characteristics of mild facial asymmetry with unaffected neurocranium and eyeballs, along with esotropia, amblyopia and/or convergent strabismus and occasionally submucous cleft palate. Transmission is autosomal dominant. There have been no further descriptions in the literature since 1979.
A very rare type of heart-hand syndrome described in three members of a Spanish family to date. The syndrome has characteristics of cardiac conduction defect (sick sinus, bundle-branch block) and brachydactyly, resembling brachydactyly type C of the hands, affecting principally the middle phalanges in conjunction with an extra ossicle on the proximal phalanx of both index fingers. Feet abnormalities are more subtle.
Progressive familial heart block type II (PFHB2) is an autosomal dominant disorder, similar to type I progressive familial heart block (PFHB1; see 113900). The pattern of PFHB2, however, tends to develop along the lines of a sinus bradycardia with a left posterior hemiblock, presenting clinically as syncopal episodes, Stokes-Adams seizures, or sudden death when complete heart block supervenes (Brink and Torrington, 1977).
A type of third degree heart block in which the escape rhythm arises at the atrioventricular node, which produces a narrow QRS complex.
Hand-foot-genital syndrome (HFGS) is characterized by limb malformations and urogenital defects. Mild bilateral shortening of the thumbs and great toes, caused primarily by shortening of the distal phalanx and/or the first metacarpal or metatarsal, is the most common limb malformation and results in impaired dexterity or apposition of the thumbs. Urogenital abnormalities include: abnormalities of the ureters and urethra and various degrees of incomplete müllerian fusion in females; hypospadias of variable severity with or without chordee in males. Vesicoureteral reflux, recurrent urinary tract infections, and chronic pyelonephritis are common; fertility is normal.
The presence of a longitudinal vaginal septum, thereby creating a vaginal duplication.
Ossification of carpal bones occurs later than age-adjusted norms.
Aplasia of the hallux, that is, a development defect such that the big toe does not develop.
Hairy elbows is a rare form of localized hypertrichosis. The lanugo type of hair usually appears in infancy, becomes coarser during early childhood, and regresses at adolescence (summary by Visser et al., 2002).
A rare osteogenesis imperfecta-like disorder, described in two patients to date, with clinical characteristics of persistent wormian bones, blue sclera, mandibular hypoplasia, shallow glenoid fossa, and campomelia. There have been no further descriptions in the literature since 1986.
Gout is a common disorder resulting from tissue deposition of monosodium urate crystals as a consequence of hyperuricemia. Patients with gout experience very painful attacks caused by precipitation of urate in joints, which triggers subsequent inflammation. Elevated serum uric acid concentration is a key risk factor for gout (summary from Matsuo et al., 2009 and Woodward et al., 2011). Genetic Heterogeneity of Serum Uric Acid Concentration Quantitative Trait Loci See also UAQTL2 (see 612076), conferred by variation in the SLC2A9 gene (606142) on chromosome 4p; UAQTL4 (612671), conferred by variation in the SLC17A3 gene (611034) on chromosome 6p21; UAQTL5 (614746), associated with a SNP on chromosome 19q13; and UAQTL6 (614747), associated with a SNP on chromosome 1.
A very rare syndrome characterised by the association of multinodular goitre, cystic renal disease and digital anomalies. It has been described in two siblings and one unrelated child. The two siblings had digitalised thumbs and preaxial polydactyly, the third child had normal thumbs and postaxial polydactyly. Goitre and/or digitalised thumbs and/or polydactyly were present in other members of families. This syndrome seems to be transmitted as an autosomal dominant trait with variable expression and incomplete penetrance.
An extremely rare syndrome involving goniodysgenesis, intellectual disability and short stature in addition to microcephaly, short nose, small hands and ears, and that has been seen in one family to date. There have been no further descriptions in the literature since 1992.
Generalized glucocorticoid resistance is an autosomal dominant disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of clinical stigmata of Cushing syndrome. The clinical expression of the disease is variable. Common features include hypoglycemia, hypertension, and metabolic alkalosis. In females, overproduction of adrenal androgens has been associated with infertility, male-pattern baldness, hirsutism, and menstrual irregularities. Other features include chronic fatigue and profound anxiety (summary by Chrousos et al., 1983; Donner et al., 2013).
Glomuvenous malformations, also known as 'venous malformations with glomus cells' or glomangiomas, are similar to mucocutaneous venous malformations (VMCM; 600195), but clinically are distinguishable: they have a cobble-stone appearance, have a consistency harder than that of venous malformations, and are painful on palpation. Histologically, GVMs are distinguishable by the presence of pathognomonic rounded cells (glomus cells) around the distended vein-like channels. The term glomus (Latin for ball) stems from the morphologically similar contractile cells of the Sucquet-Hoyer arteriovenous anastomoses in glomus bodies that are involved in cutaneous thermoregulation. Glomus cells in GVMs appear to be incompletely or improperly differentiated vascular smooth muscle cells, since they stain positively with smooth muscle cell alpha-actin (102620) and vimentin (193060) (summary by Brouillard et al., 2002). The genetic distinctness of glomuvenous malformations from mucocutaneous venous malformations is indicated by the fact that mutations have been found in the TIE2/TEK gene (600221) in mucocutaneous venous malformations and not in glomuvenous malformations.
A reduction in the count of nephrons per kidney.
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Patients with ASGD4 have been reported with iridogoniodysgenesis or Peters anomaly subtypes. Iridogoniodysgenesis, which is characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma, is the result of aberrant migration or terminal induction of the neural crest cells involved in the formation of the anterior segment of the eye (summary by Mears et al., 1996). Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (Peters, 1906).
Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, 155600), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (249400), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by Kinsler et al., 2008; Kinsler et al., 2012). Spitz nevi are benign melanocytic melanomas composed of epithelioid or spindle cell melanocytes. They usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms (summary by Sarin et al., 2013). Nevus spilus, also known as speckled lentiginous nevus, is a congenital hyperpigmented patch that progressively evolves, with affected individuals developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanomas (summary by Sarin et al., 2014).
Greater than average forward and/or lateral protrusion of the supraorbital portion of the frontal bones.
Autosomal dominant limb-girdle muscular dystrophy-2 is a myopathy characterized by proximal muscle weakness primarily affecting the lower limbs, but also affecting the upper limbs in most patients. Affected individuals also have distal muscle weakness of the hands and lower leg muscles. There is variability in presentation and progression. Some patients present in early childhood with mildly delayed walking and difficulty running and jumping, whereas others present as adults with mainly pelvic-girdle weakness. Patients with early onset tend to have a more severe disorder, and may develop contractures, loss of independent ambulation, and respiratory insufficiency. Muscle biopsy shows dystrophic changes with abnormal nuclei, rimmed vacuoles, and filamentous inclusions (summary by Melia et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511).
Bradyopsia is a rare condition that affects vision. The term ""bradyopsia"" is from the Greek words for slow vision. In affected individuals, the eyes adapt more slowly than usual to changing light conditions. For example, people with this condition are blinded for several seconds when going from a dark environment into a bright one, such as when walking out of a darkened movie theater into daylight. Their eyes also have trouble adapting from bright light to dark conditions, such as when driving into a dark tunnel on a sunny day.Some people with bradyopsia also have difficulty seeing some moving objects, particularly small objects moving against a bright background. As a result, they often have trouble watching or participating in sports with a ball, such as soccer or tennis. People with bradyopsia can have reduced sharpness (acuity) of vision, although acuity may depend on the conditions under which vision is tested. Visual acuity may appear to be severely affected if it is tested under bright lights, but it can be near normal if tested in a dim environment. The ability to see colors and distinguish between them is normal.The vision problems associated with bradyopsia become apparent in early childhood. They are usually stable, which means they do not worsen over time.
Complete or partial merging of the posterior part of adjacent ribs.
Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for ""microcephaly primary hereditary"") is a condition in which infants are born with a very small head and a small brain. The term ""microcephaly"" comes from the Greek words for ""small head.""Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal.MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed.People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems.
Branchiootorenal spectrum disorder (BORSD) is characterized by malformations of the outer, middle, and inner ear associated with conductive, sensorineural, or mixed hearing impairment, branchial fistulae and cysts, and renal malformations ranging from mild renal hypoplasia to bilateral renal agenesis. Some individuals progress to end-stage renal disease (ESRD) later in life. Extreme variability can be observed in the presence, severity, and type of branchial arch, otologic, audiologic, and renal abnormality from right side to left side in an affected individual and also among individuals in the same family.
A progressive form of hearing impairment.
Disease with characteristics of short stature and premature degenerative arthropathy. It has been described in one multigenerational South African family of English white descent. The main clinical features may include proportionate short stature (less than fifth percentile for age), stocky habitus and early-onset progressive osteoarthropathy of the weight-bearing joints. Radiographic features are flattened vertebral bodies with sclerosis and prominent endplate irregularity and flattened femoral epiphyses. Caused by mutation in the aggrecan gene (AGC1, locus 15q26.1) and transmitted as an autosomal dominant trait.
An irregular surface of the vertebral end plates, which are normally relatively smooth.
An abnormal flattening of the proximal epiphysis of the femur.
Myosin storage myopathy, also known as hyaline body myopathy, is a congenital myopathy characterized by the accumulation of ATPase and antibody positive myosin in hyaline subsarcolemmal bodies in type I muscle fibers. The clinical features are variable, with different patients displaying proximal, scapuloperoneal, or generalized weakness and progressive or nonprogressive courses (summary by Dye et al., 2006).
Muscular atrophy in the distribution of shoulder girdle and peroneal muscles.
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
RASA1-related disorders are characterized by the presence of multiple small (1-2 cm in diameter) capillary malformations mostly localized on the face and limbs. About 30% of affected individuals also have associated arteriovenous malformations (AVMs) and/or arteriovenous fistulas (AFVs), fast-flow vascular anomalies that typically arise in the skin, muscle, bone, spine, and brain; life-threatening complications of these lesions can include bleeding, congestive heart failure, and/or neurologic consequences. Symptoms from intracranial AVMs/AVFs appear to occur early in life. Several individuals have RASA1-related Parkes Weber syndrome (multiple micro-AVFs associated with a cutaneous capillary stain and excessive soft-tissue and skeletal growth of an affected limb).
GDAP1-related hereditary motor and sensory neuropathy (GDAP1-HMSN) is a peripheral neuropathy (also known as a subtype of Charcot-Marie-Tooth disease) that typically affects the lower extremities earlier and more severely than the upper extremities. As the neuropathy progresses, the distal upper extremities also become severely affected. Proximal muscles can also become weak. Age at onset ranges from infancy to early childhood. In most cases, disease progression causes disabilities within the first or second decade of life. At the end of the second decade, most individuals are wheelchair bound. Disease progression varies considerably even within the same family. The neuropathy can be either of the demyelinating type with reduced nerve conduction velocities or the axonal type with normal nerve conduction velocities. Vocal cord paresis is common. Intelligence is normal. Life expectancy is usually normal, but on occasion may be reduced because of secondary complications.
Increased side-to-side width of a metatarsal bone.
Coronary artery disease (CAD) and its most important complication, acute myocardial infarction (MI), are leading causes of death and disability in the developed world. Multiple risk factors for CAD/MI have been identified, including family history, hypertension, hypercholesterolemia, obesity, smoking, and diabetes. Several genomewide scans of affected sib pairs have identified susceptibility loci for CAD, e.g., 607339 and 300464.
The association of ectodermal dysplasia (hypotrichosis and hypohidrosis) with acanthosis nigricans. So far, only eight cases have been described in the literature. Other clinical features may include palmoplantar hyperkeratosis, nail dystrophy, intellectual deficit and hypodontia. Transmission is autosomal recessive.
An autosomal recessive disorder caused by mutations in the HGF gene, encoding hepatocyte growth factor receptor. It is characterized by profound deafness.
A hereditary demyelinating motor and sensory neuropathy with characteristics of slowed nerve conduction velocities in the absence of clinically apparent neurological deficits, gait abnormalities or muscular atrophy, associated with a germline mutation in the ARGHEF10 gene.
Reduced muscle tone secondary to an abnormality of the central nervous system.
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella.
Autosomal dominant deafness-41 (DFNA41) is characterized by onset of progressive sensorineural hearing loss usually in the second decade. The hearing loss is severe and ultimately affects all frequencies. Exposure to noise exacerbates the hearing loss, particularly at high frequencies (summary by Yan et al., 2013).
Aspirin (acetylsalicylic acid) is a classic nonsteroidal antiinflammatory agent that irreversibly inhibits type I cyclooxygenase (PTGS1, or COX1; 176805) in platelets, resulting in decreased production of thromboxane A2 (TXA2) and inhibition of platelet aggregation. Because of this feature, it is used therapeutically to prevent cardiothrombotic events. Individuals show a variable response to the drug, referred to as aspirin ineffectiveness or resistance, in which not all individuals or populations appear to receive the full prophylactic or therapeutic benefits (summary by Zhou et al., 2011). Halushka and Halushka (2002) discussed a possible basis for resistance to the cardioprotective effect of aspirin.
A primary immunodeficiency characterised by neutrophilia with severe neutrophil dysfunction, leucocytosis, a predisposition to bacterial infections and poor wound healing, including an absence of pus in infected areas. The disease is due to a point dominant negative mutation in the RAC2 gene causing decreased Rac2 protein expression and a defect in a signalling pathway controlling shape change/motility of neutrophils as well as assembly and activation of NADPH oxidase. The mode of transmission is unknown.
Ketosis-resistant diabetes is a synonym for type II diabetes. This term thus refers to a form of type II diabetes in which patients are dependent on insulin.
The presence of abnormal calcium deposition lesions in the pancreas.
Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process (summary by Imai et al., 2003). For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230).
The autoimmune thyroid disorders, or AITDs, comprise 2 related disorders, Graves disease (GD; 275000) and Hashimoto thyroiditis (HT; 140300). See 608173.
Nablus mask-like facial syndrome (NMLFS) is a rare entity defined by distinctive facial features, including blepharophimosis, tight-appearing glistening facial skin, an abnormal hair pattern with an upswept frontal hairline, sparse arched eyebrows, flat and broad nose, long philtrum, distinctive ears, and a happy demeanor (summary by Jain et al., 2010).
Transient neonatal zinc deficiency occurs in breast-fed infants as a consequence of low milk zinc concentration in their nursing mothers, which cannot be corrected by maternal zinc supplementation. A large amount of zinc, an essential trace mineral, is required for normal growth particularly in infants, and breast milk normally contains adequate zinc to meet the requirement for infants up to 4 to 6 months of age. Zinc deficiency can lead to dermatitis, alopecia, decreased growth, and impaired immune function. The disorder shows autosomal dominant inheritance with incomplete penetrance (summary by Chowanadisai et al., 2006). Some aspects of TNZD resemble the more severe disorder acrodermatitis enteropathica (AEZ; 201100), an autosomal recessive disorder caused by mutation in the zinc transporter SLC39A4 (607059). However, infants with transient neonatal zinc deficiency do not require zinc supplementation following weaning and have normal zinc absorption, whereas those with AEZ require lifelong zinc supplementation (summary by Chowanadisai et al., 2006).
An impairment of the class-switch recombination process that normally leads B lymphocytes to produce IgG, IgA, or IgE.
Muscular atrophy affecting the muscles of the limb girdle.
Periventricular heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Heterotopia means ""out of place."" In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. The neurons then migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. In periventricular heterotopia, some neurons fail to migrate to their proper position and form clumps around the ventricles.Periventricular heterotopia usually becomes evident when seizures first appear, often during the teenage years. The nodules around the ventricles are then typically discovered when magnetic resonance imaging (MRI) studies are done. Affected individuals usually have normal intelligence, although some have mild intellectual disability. Difficulty with reading and spelling (dyslexia) and movement problems have been reported in some people with periventricular heterotopia.Less commonly, individuals with periventricular heterotopia may have other features including more severe brain malformations, small head size (microcephaly), developmental delays, recurrent infections, blood vessel abnormalities, stomach problems, or lung disease. Periventricular heterotopia may also occur in association with other conditions such as Ehlers-Danlos syndrome, which results in extremely flexible joints, skin that stretches easily, and fragile blood vessels.
Familial temporal lobe epilepsy (FTLE, ETL) is a genetically heterogeneous syndrome characterized by relatively benign simple or complex partial seizures with intense psychic or autonomic auras (Berkovic et al., 1996). For a discussion of genetic heterogeneity of temporal lobe epilepsy, see ETL1 (600512).
An abnormality of eye movement characterized by impairment of fast (saccadic) eye movements.
The hereditary sensory and autonomic neuropathies (HSAN), which are also referred to as hereditary sensory neuropathies (HSN) in the absence of significant autonomic features, are a genetically and clinically heterogeneous group of disorders associated with sensory dysfunction. For a discussion of genetic heterogeneity of HSAN, see HSAN1A (162400).
An axonal neuropathy of peripheral sensory nerves.
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of genetic heterogeneity of autism, see 209850. See also chromosome 13q14 deletion syndrome (613884) in which retinoblastoma and mental retardation are features.
Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs most often in the skin, but may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes (summary by Habif, 2010). For a discussion of genetic heterogeneity of cutaneous malignant melanoma (CMM), see 155600.
Underdevelopment of the helix, i.e., of the outer rim of the pinna.
Pontocerebellar hypoplasia (PCH) refers to a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. Clinical features vary, but usually include severe developmental delay, dysmorphic features, seizures, and early death (summary by Durmaz et al., 2009). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
Diaphanospondylodysostosis is a rare, recessively inherited, perinatal lethal skeletal disorder. The primary skeletal characteristics include small chest, abnormal vertebral segmentation, and posterior rib gaps containing incompletely differentiated mesenchymal tissue. Consistent craniofacial features include ocular hypertelorism, epicanthal folds, depressed nasal bridge with short nose, and low-set ears. The most commonly described extraskeletal finding is nephroblastomatosis with cystic kidneys, but other visceral findings have been described in some cases (summary by Funari et al., 2010).
Lack of formation and mineralization of the ribs in utero.
Radiolucent focal defect of the posterior portion of a rib shaft. The 'gaps' may lead to flail chest.
Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is an immunoosseous dysplasia combining the typical metaphyseal and vertebral bone lesions of spondyloenchondrodysplasia (SPENCD) with immune dysfunction and neurologic involvement. The skeletal dysplasia is characterized by radiolucent and irregular spondylar and metaphyseal lesions that represent islands of chondroid tissue within bone. The vertebral bodies show dorsally accentuated platyspondyly with disturbance of ossification. Clinical abnormalities such as short stature, rhizomelic micromelia, increased lumbar lordosis, barrel chest, facial anomalies, and clumsy movements may be present (Menger et al., 1989). Central nervous system involvement includes spasticity, mental retardation, and cerebral calcifications, and immune dysregulation ranges from autoimmunity to immunodeficiency. Neurologic and autoimmune manifestations have been observed in different combinations within a single family, suggesting that this disorder may be defined by specific radiographic features but has remarkably pleiotropic manifestations (Renella et al., 2006). Briggs et al. (2016) also noted variability in skeletal, neurologic, and immune phenotypes, which was sometimes marked between members of the same family. Classification of the Enchondromatoses In their classification of the enchondromatoses, Spranger et al. (1978) called Ollier disease and Maffucci syndrome types I and II enchondromatosis, respectively; metachondromatosis (156250), type III; and spondyloenchondrodysplasia (SPENCD), also called spondyloenchondromatosis, type IV; enchondromatosis with irregular vertebral lesions, type V; and generalized enchondromatosis, type VI. Halal and Azouz (1991) added 3 tentative categories to the 6 in the classification of Spranger et al. (1978). Pansuriya et al. (2010) suggested a new classification of enchondromatosis (multiple enchondromas).
A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size.
Increased susceptibility to upper and lower respiratory tract infections, as manifested by recurrent episodes of upper and lower respiratory tract infections.
Any anomaly of the progression of electrical impulses through the heart.
Localized autosomal recessive hypotrichosis is characterized by fragile hairs that break easily, leaving short, sparse scalp hairs. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas. In some patients with congenital hypotrichosis, monilethrix-like hairs showing elliptical nodes have been observed (summary by Schaffer et al., 2006). Genetic Heterogeneity of Autosomal Recessive Localized Hypotrichosis LAH2 (HYPT7; 604379) is caused by mutation in the LIPH gene (607365) on chromosome 3q27, and LAH3 (HYPT8; 278150) is caused by mutation in the LPAR6 (P2RY5) gene (609239) on chromosome 13q14.12-q14.2. See also hypotrichosis and recurrent skin vesicles (613102), which is caused by mutation in the DSC3 gene (600271).
Familial adult myoclonic epilepsy-2 is an autosomal dominant neurologic disorder characterized by rhythmic myoclonic jerks of cortical origin. Some affected individuals have generalized tonic-clonic seizures, and rare patients show cognitive decline (summary by De Fusco et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of familial adult myoclonic epilepsy, see FAME1 (601068).
1p36 deletion syndrome is characterized by typical craniofacial features consisting of straight eyebrows, deeply set eyes, midface retrusion, wide and depressed nasal bridge, long philtrum, pointed chin, large, late-closing anterior fontanel (77%), microbrachycephaly (65%), epicanthal folds (50%), and posteriorly rotated, low-set, abnormal ears. Other characteristic findings include brachy/camptodactyly and short feet. Developmental delay/intellectual disability of variable degree are present in all, and hypotonia in 95%. Seizures occur in 44%-58% of affected individuals. Other findings include structural brain abnormalities (88%), congenital heart defects (71%), eye/vision problems (52%), hearing loss (47%), skeletal anomalies (41%), abnormalities of the external genitalia (25%), and renal abnormalities (22%).
Lack of prominence of the nose resulting from a posteriorly-placed nasal ridge.
Hypoplasia (congenital reduction in size) of the fifth finger, also known as the little finger.
LAMA2-related muscular dystrophy is a disorder that causes weakness and wasting (atrophy) of muscles used for movement (skeletal muscles). This condition varies in severity, from a severe, early-onset type to a milder, late-onset form.Early-onset LAMA2-related muscular dystrophy is apparent at birth or within the first few months of life. It is considered part of a class of muscle disorders called congenital muscular dystrophies and is sometimes called congenital muscular dystrophy type 1A. Affected infants may have severe muscle weakness, lack of muscle tone (hypotonia), little spontaneous movement, and joint deformities (contractures). Weakness of the muscles in the face and throat can result in feeding difficulties and an inability to grow and gain weight at the expected rate. Respiratory insufficiency, which occurs when muscles in the chest are weakened, causes a weak cry and breathing problems that can lead to frequent, potentially life-threatening lung infections.As affected children grow, they often develop an abnormal, gradually worsening side-to-side curvature of the spine (scoliosis) and inward curvature of the back (lordosis). Children with early-onset LAMA2-related muscular dystrophy often do not develop the ability to walk. Difficulty with speech may result from weakness of the facial muscles and an enlarged tongue. Seizures occur in about a third of individuals with early-onset LAMA2-related muscular dystrophy; rarely, heart complications occur in this form of the disorder.Symptoms of late-onset LAMA2-related muscular dystrophy become evident later in childhood or adulthood, and are similar to those of a group of muscle disorders classified as limb-girdle muscular dystrophies. In late-onset LAMA2-related muscular dystrophy, the muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area, and thighs. Children with late-onset LAMA2-related muscular dystrophy sometimes have delayed development of motor skills such as walking, but generally achieve the ability to walk without assistance. Over time, they may develop rigidity of the back, joint contractures, scoliosis, and breathing problems. However, most affected individuals retain the ability to walk and climb stairs.
Adult-onset foveomacular vitelliform dystrophy, also known as adult vitelliform macular dystrophy, adult-type foveomacular dystrophy, adult vitelliform macular degeneration, pseudovitelliform macular degeneration, and adult-onset foveomacular pigment epithelial dystrophy, is characterized by a solitary, oval, slightly elevated yellowish subretinal lesion of the fovea that is similar in appearance to the vitelliform or egg-yolk stage of Best disease (153700). Initially the yellow lesion may be present in only one eye. The size is generally one-third to one disc diameter, and small yellow flecks are seen in the paracentral lesion. Patients usually become symptomatic in the fourth or fifth decade of life with a protracted decrease of visual acuity and mild metamorphopsia. Electrooculographic testing reveals a normal or only slightly reduced Arden ratio, which is intensely abnormal in Best disease. The prognosis is optimistic, as most patients retain reading vision throughout life (Felbor et al., 1997; Yamaguchi et al., 2001). For a discussion of genetic heterogeneity of vitelliform macular dystrophy, see VMD1 (153840).
Nonimmune chronic idiopathic neutropenia of adults (NI-CINA) is a relatively mild form of neutropenia diagnosed in adults but predisposing to leukemia in a subset of patients (Papadaki et al., 2002).
Altmann (1955) was the first to describe a congenital aural atresia (CAA) classification, which has been modified over the years (Cremers et al., 1988; Schuknecht, 1989; Jahrsdoerfer et al., 1992). In CAA type I, there is bony or fibrous atresia of the lateral part of the external auditory canal and an almost normal medial part and middle ear. CAA type II is the most frequent type and is characterized by partial or total aplasia of the external auditory canal. CAA type IIA involves an external auditory canal with either complete bony atresia of the medial part or partial aplasia that ends blindly in a fistula leading to a rudimentary tympanic membrane. CAA type IIB is characterized by bony stenosis of the total length of the external auditory canal. CAA type III involves bony atresia of the external auditory canal and a very small or absent middle-ear cavity (summary by Feenstra et al., 2011).
Personality trait related to tendency to respond to threat, frustration or a loss with negative emotions (e.g., ANGER; ANXIETY; FRUSTRATION; embarrassment and sadness).
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
A rare form of axonal Charcot-Marie-Tooth peripheral sensorimotor polyneuropathy with characteristics of a mild phenotype, onset during the second decade of life and very slow progression. Walking ability is retained. Caused by mutations in the GDAP1 gene (8q13.3), encoding a protein required for mitochondrial fission.
Patients with MVP2 have nonsyndromic MVP of variable severity inherited as an autosomal dominant trait. For a general phenotypic description and discussion of genetic heterogeneity of mitral valve prolapse, see MVP1 (157700).
Hypotrichosis-lymphedema-telangiectasia syndrome is an autosomal recessive disorder characterized by these 3 features, which begin at birth or in early childhood and are progressive (summary by Irrthum et al., 2003).
Alzheimer disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. This disorder usually appears in people older than age 65, but less common forms of the disease appear earlier in adulthood.Memory loss is the most common sign of Alzheimer disease. Forgetfulness may be subtle at first, but the loss of memory worsens over time until it interferes with most aspects of daily living. Even in familiar settings, a person with Alzheimer disease may get lost or become confused. Routine tasks such as preparing meals, doing laundry, and performing other household chores can be challenging. Additionally, it may become difficult to recognize people and name objects. Affected people increasingly require help with dressing, eating, and personal care.As the disorder progresses, some people with Alzheimer disease experience personality and behavioral changes and have trouble interacting in a socially appropriate manner. Other common symptoms include agitation, restlessness, withdrawal, and loss of language skills. People with this disease usually require total care during the advanced stages of the disease. Affected individuals usually survive 8 to 10 years after the appearance of symptoms, but the course of the disease can range from 1 to 25 years. Death usually results from pneumonia, malnutrition, or general body wasting (inanition).Alzheimer disease can be classified as early-onset or late-onset. The signs and symptoms of the early-onset form appear before age 65, while the late-onset form appears after age 65. The early-onset form is much less common than the late-onset form, accounting for less than 5 percent of all cases of Alzheimer disease.
Craniolenticulosutural dysplasia is an autosomal recessive disorder characterized by facial dysmorphism, late-closing fontanels, cataract, and skeletal defects (summary by Boyadjiev et al., 2011).
Muscle hypertrophy affecting the calf muscles.
A segmental pattern of demyelination and regeneration (remyelination) affecting peripheral nerves.
A skeletal dysplasia with clinical characteristics of short stature of variable degrees with short limbs, brachydactyly and narrow thorax. Affected patients have normal intelligence. Radiographically, cone-shaped epiphyses are observed in the hands, the proximal part of the femur and to a variable degree, at the shoulders, knees, and ankles. Homozygous mutations in the Indian hedgehog homolog gene (IHH; 2q33-q35), outside the region where brachydactyly type A-1 mutations are clustered, have been identified in affected patients. The condition is transmitted as an autosomal recessive trait.
An abnormal enlargement of the distal epiphysis of the femur.
Congenital defects of bile acid synthesis are autosomal recessive disorders characterized by neonatal onset of progressive liver disease with cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract resulting from a primary failure to synthesize bile acids. Affected infants show failure to thrive and secondary coagulopathy. In most forms of the disorder, there is a favorable response to oral bile acid therapy (summary by Cheng et al., 2003). Genetic Heterogeneity of Congenital Defects in Bile Acid Synthesis There are several disorders that result from defects in bile acid synthesis. See CBAS2 (235555), caused by mutation in the delta(4)-3-oxosteroid 5-beta-reductase gene (AKR1D1; 604741) on chromosome 7q33; CBAS3 (613812), caused by mutation in the 7-alpha hydroxylase gene (CYP7B1; 603711) on chromosome 8q12; CBAS4 (214950), caused by mutation in the AMACR gene (604489) on chromosome 5p13; CBAS5 (616278), caused by mutation in the ABCD3 gene (170995) on chromosome 1p21; and CBAS6 (617308), caused by mutation in the ACOX2 gene (601641) on chromosome 3p14. See also progressive familial intrahepatic cholestasis (PFIC1; 211600), which has a similar phenotype.
A very rare genetic disorder with clinical characteristics of elevated serum bile acid concentrations, itching and fat malabsorption reported in patients of Old Order Amish descent. Can be caused by mutation in the TJP2 gene on chromosome 9q21, the BAAT gene on chromosome 9q31, or the EPHX1 gene on chromosome 1q42.
Benign familial neonatal-infantile seizures is an autosomal dominant disorder in which afebrile seizures occur in clusters during the first year of life, without neurologic sequelae (Shevell et al., 1986). For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764). BFIS1 has a slightly later onset than BFIS3, while benign neonatal seizures (see BFNS1, 121200) has a slightly earlier onset.
Lack of observable abnormal electroencephalographic (EEG) patterns in an individual with a history of seizures. About half of individuals with epilepsy show interictal epileptiform discharges upon the first investigation. The yield can be increased by repeated studies, sleep studies, or by ambulatory EEG recordings over 24 hours. Normal interictal EEG is a sign that can be useful in the differential diagnosis.
For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
A progressive form of sensorineural hearing impairment.
Charcot-Marie-Tooth neuropathy type 2E/1F (CMT2E/1F) is characterized by a progressive peripheral motor and sensory neuropathy with variable clinical and electrophysiologic expression. Disease onset ranges from the first to the fifth decade of life; in some cases disease onset can be in infancy. Affected individuals have difficulty walking and running because of progressive distal weakness and wasting of the muscles of the lower limbs. Paresis in the distal part of the lower limbs varies from mild weakness to a complete paralysis of the distal muscle groups. Tendon reflexes are diminished or absent. Sensory signs are not prominent but are present in all affected individuals. Pes cavus, hammer toes, and claw hands are frequently observed. Ambulation is generally preserved.
The presence of excessive redundant myelin in the peripheral nerve sheath.
Groups of small caliber axons in peripheral nerve biospies indicative of axonal regeneration.
An axonal peripheral sensorimotor polyneuropathy associated with pyramidal involvement. So far, it has been described in 13 members of a large Tunisian family. Onset occurred during the first decade of life with progressive distal atrophy involving both the upper and lower limbs, associated with a mild pyramidal syndrome (brisk patellar and upper limb reflexes, absent ankle reflexes and unattainable plantar reflexes). Transmitted in an autosomal recessive manner and the disease-causing locus has been mapped to 8q13-21.1.
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members as well as individuals expressing more than one variant have been reported, suggesting that the distinctions among these variants may be artificial. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life (summary by Wu et al., 2004 and Zhang et al., 2012). For a discussion of genetic heterogeneity of porokeratosis, see 175800.
A Noonan-related syndrome with characteristics of facial anomalies suggestive of Noonan syndrome, a distinctive hair anomaly described as loose anagen hair syndrome, frequent congenital heart defects, distinctive skin features with darkly pigmented skin, keratosis pilaris, eczema or occasional neonatal ichthyosis and short stature, often associated with a growth hormone deficiency and psychomotor delay. There is evidence that this syndrome is caused by heterozygous mutation in the SHOC2 gene on chromosome 10q25.
Childhood absence epilepsy is a condition characterized by recurrent seizures (epilepsy). This condition begins in childhood, usually between ages 3 and 8. Affected children have absence seizures (also known as petit mal seizures), which are brief episodes of impaired consciousness that look like staring spells. During seizures, children are not aware of and do not respond to people or activities around them. The seizures usually last several seconds and they occur often, up to 200 times each day.Some affected individuals have febrile seizures before they develop childhood absence epilepsy. Febrile seizures are involuntary muscle contractions (convulsions) brought on by a high body temperature (fever).In most people with childhood absence epilepsy, the absence seizures disappear in adolescence. However, some affected individuals continue to have absence seizures into adulthood, or they may develop generalized tonic-clonic seizures, which cause muscle rigidity, convulsions, and loss of consciousness, or myoclonic seizures, which are characterized by rapid, uncontrolled muscle jerks.
IRAK4 deficiency is an autosomal recessive primary immunodeficiency that impairs Toll (see TLR4; 603030)/IL1R (see IL1R1; 147810) immunity, except for the TLR3 (603029)- and TLR4-interferon-alpha (IFNA; 147660)/beta (IFNB; 147640) pathways (Ku et al., 2007).
An autoimmune disorder comprising tubulointerstitial nephritis and uveitis.
Acute inflammation of the kidney affecting the interstitium of the kidneys surrounding the tubules.
Acute renal failure with resolution of manifestations.
An extremely rare ectodermal dysplasia syndrome with characteristics of hypotrichosis universalis with mild to severe scarring alopecia, acro-osteolysis, onychogryphosis, thin and tapered fingertips, periodontitis and caries leading to premature teeth loss, linear or reticular palmoplantar keratoderma and erythematous, scaling, psoriasis-like skin lesions on arms and legs. Lingua plicata and ventricular tachycardia have also been observed.
An extremely rare ectodermal dysplasia syndrome with characteristics of premature loss of curly, brittle, dry hair, premature loss of teeth due to caries, nail dystrophy with thickening of the finger and toe-nails, acral keratoderma and hypohidrosis. Additionally, sparse eyebrows and eyelashes, receding frontal hairline and flattened malar region are associated. The severity of features appears to increase with age.
The osteopetroses are a heterogeneous group of genetic disorders characterized by increased bone density due to impaired bone resorption by osteoclasts. Autosomal dominant osteopetrosis-1 is characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate (summary by Van Hul et al., 2002). Genetic Heterogeneity of Autosomal Dominant Osteopetrosis Autosomal dominant osteopetrosis-2 (OPTA2; 166600) is caused by mutation in the CLCN7 gene (602727) on chromosome 16p13. Autosomal dominant osteopetrosis-3 (OPTA3; 618107) is caused by mutation in the PLEKHM1 gene (611466) on chromosome 17q21.
An abnormal increase of bone mineral density with generalized involvement of the skeleton.
A very rare complex ichthyosis syndrome with characteristics of scalp hypotrichosis, scarring alopecia, ichthyosis and sclerosing cholangitis. The ichthyosis presents with diffuse white scales sparing the skin folds and is accompanied by scalp hypotrichosis, cicatricial alopecia, and sparse eyelashes/eyebrows. Additional manifestations may include oligodontia, hypodontia and enamel dysplasia. All patients present with neonatal sclerosing cholangitis with jaundice and pruritus, hepatomegaly and biochemical cholestasis. Caused by a mutation in the CLDN1 gene on chromosome 3q28 coding for the tight junction protein claudin-1. Autosomal recessive pattern of inheritance.
A supranuclear gaze palsy is an inability to look in a vertical direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal. [HPO:probinson, pmid:20671861]
A reduction in the rate of cholesterol esterification.
Decreased ability to react to a delayed hypersensitivity skin test.
Death in during childhood, defined here as between the ages of 2 and 10 years.
A rare clinical variant of epidermolytic ichthyosis, with manifestations of blistering phenotype at birth and the development from early infancy of annular polycyclic erythematous scales on the trunk and extremities. It has been reported in less than 10 families. The disease is caused by mutations in the KRT1 (12q11-q13) and KRT10 (17q21-q23) genes, encoding keratins 1 and 10 respectively. These mutations impair keratin filament formation and weaken the structural stability of the keratinocyte cytoskeleton. Transmission is autosomal dominant.
A congenital abnormality characterized by the presence of two abnormally small eye globes.
Underdevelopment of the ventral portion of the pons.
The presence of an increased number of twists and turns of the retinal arterioles.
An abnormal gait pattern characterized by the failue of the heel to contact the floor at the onset of stance during gait.
Weakness of the muscles involved in neck flexion (sternocleidomastoid, longus capitus, longus colli, and scalenus anterior).
Abnormal function of a sphincter of the urinary bladder.
An abnormal enlargement of the sella turcica.
Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). Genetic Heterogeneity of Familial Atrial Fibrillation ATFB1 shows linkage to chromosome 10q22-q24. ATFB2 (608988) maps to chromosome 6q. ATFB3 (607554) is caused by mutation in the KCNQ1 gene (607542) on chromosome 11. ATFB4 (611493) is caused by mutation in the KCNE2 gene (603796) on chromosome 21. Variants in a region of chromosome 4q25 are associated with ATFB5 (611494). ATFB6 (612201) is caused by mutation in the NPPA gene (108780) on chromosome 1p36. ATFB7 (612240) is caused by mutation in the KCNA5 gene (176267) on chromosome 12p13. ATFB8 (613055) maps to chromosome 16q22. ATFB9 (613980) is caused by mutation in the KCNJ2 gene (600681) on chromosome 17q24.3. ATFB10 (614022) is caused by mutation in the SCN5A gene (600163) on chromosome 3p21. ATFB11 (614049) is caused by mutation in the GJA5 (121013) gene on chromosome 1q21.1. ATFB12 (614050) is caused by mutation in the ABCC9 gene (601439) on chromosome 12p12.1. ATFB13 (615377) is caused by mutation in the SCN1B gene (600235) on chromosome 19q13. ATFB14 (615378) is caused by mutation in the SCN2B gene (601327) on chromosome 11q23. ATFB15 (615770) is caused by mutation in the NUP155 gene (606694) on chromosome 5p13. ATFB16 (see 613120) is caused by mutation in the SCN3B gene (608214) on chromosome 11q24. ATFB17 (see 611819) is caused by mutation in the SCN4B gene (608256) on chromosome 11q23. ATFB18 (617280) is caused by mutation in the MYL4 gene (160770) on chromosome 17q21. Olesen et al. (2014) analyzed 192 Danish Caucasian patients with onset of lone atrial fibrillation before the age of 40 years for the presence of rare variants in 14 AF-associated genes and found that 29 (7.6%) alleles harbored a very rare variant (minor allele frequency less than 1%), a significantly higher percentage than that found in 6,503 individuals in the NHLBI Exome Variant Server database (4.1%; p = 0.0012). Twenty-four of the 29 rare variants found in the lone AF patient cohort had previously been studied, with 23 (96%) showing abnormal ion channel function by patch-clamp analysis. Olesen et al. (2014) suggested that rare variants in AF susceptibility genes may play a role in the pathophysiology of AF.
Multiminicore disease (MmD) is a clinically heterogeneous condition in which several subgroups can be distinguished (see 255320 and 602771). General features include neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy, which may progress slowly or remain stable. Muscle biopsy shows multiple, poorly circumscribed, short areas of sarcomere disorganization and mitochondria depletion (areas termed 'minicores') in most muscle fibers. Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present in multiminicore disease (Ferreiro and Fardeau, 2002).
Reduced strength of the axial musculature (i.e., of the muscles of the head and neck, spine, and ribs).
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
This form of isolated toenail dystrophy has been found to segregate as an autosomal dominant trait in families in which another member has the autosomal recessive skin disorder dystrophic epidermolysis bullosa (226600) or transient bullous dermolysis of the newborn (131705), the features of which include dystrophic nails. The nail changes in isolated toenail dystrophy are most severe in the great toes and consist of the nail plate being buried in the nail bed with a deformed and narrow free edge (summary by Sato-Matsumura et al., 2002). This form of toenail dystrophy is referred to here as nonsyndromic congenital nail disorder-8 (NDNC8). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
For a phenotypic description and discussion of genetic heterogeneity of migraine headaches, see MGR1 (157300).
The spectrum of frontotemporal dementia associated with GRN (also known as PGRN) mutation (FTD-GRN or FTD-PGRN) includes the behavioral variant (FTD-bv), primary progressive aphasia (PPA; further subcategorized as progressive non-fluent aphasia [PNFA] and semantic dementia [SD]), and movement disorders with extrapyramidal features such as parkinsonism and corticobasal syndrome. A broad range of clinical features both within and across families is observed. The age of onset ranges from 35 to 87 years. Behavioral disturbances are the most common early feature, followed by progressive aphasia. Impairment in executive function manifests as loss of judgment and insight. In early stages, PPA often manifests as deficits in naming, word finding, or word comprehension. In late stages, affected individuals often become mute and lose their ability to communicate. Early findings of parkinsonism include rigidity, bradykinesia or akinesia (slowing or absence of movements), limb dystonia, apraxia (loss of ability to carry out learned purposeful movements), and disequilibrium. Late motor findings may include myoclonus, dysarthria, and dysphagia. Most affected individuals eventually lose the ability to walk. Disease duration is three to 12 years.
Progressive loss of previously present language abilities.
Biotin-thiamine-responsive basal ganglia disease (BTBGD) is characterized by recurrent subacute encephalopathy manifest as confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and/or dysphagia which, if left untreated, can eventually lead to coma and even death. Dystonia and cogwheel rigidity are nearly always present; hyperreflexia, ankle clonus, and Babinski responses are common. Hemiparesis or quadriparesis may be seen. Episodes are often triggered by febrile illness or mild trauma or surgery. Less frequently, BTBGD presents as chronic or slowly progressive dystonia, seizures, and/or psychomotor delay. Although onset is usually in childhood (ages three to ten 10 years), it is extremely variable, ranging from the newborn period to adulthood. Prompt administration of biotin and thiamine early in the disease course results in partial or complete improvement within days.
Caused by mutation in the gene encoding retinaldehyde-binding protein-1. A high frequency of a distinctive form of retinal dystrophy was found to occur in northern Sweden. Typical manifestations are night blindness from early childhood and in young adults retinitis punctata albescens was observed followed by macular degeneration.
Deficiency of all vitamin K-dependent clotting factors leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. Familial multiple coagulation factor deficiency is rare. Clinical symptoms of the disease include episodes of intracranial hemorrhage in the first weeks of life, sometimes leading to a fatal outcome (Fregin et al., 2002).
Myoclonic epilepsy myopathy sensory ataxia, commonly called MEMSA, is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. The signs and symptoms of MEMSA typically appear during young adulthood. This condition had previously been known as spinocerebellar ataxia with epilepsy (SCAE).The first symptom of MEMSA is usually cerebellar ataxia, which refers to problems with coordination and balance due to defects in the part of the brain that is involved in coordinating movement (cerebellum). Recurrent seizures (epilepsy) usually develop later, often in combination with uncontrollable muscle jerks (myoclonus). The seizures usually begin in the right arm and spread to become generalized throughout the body. Additionally, affected individuals may have severe brain dysfunction (encephalopathy) or muscle weakness (myopathy). The myopathy can affect muscles close to the center of the body (proximal), such as the muscles of the hips, thighs, upper arms, or neck, or muscles farther away from the center of the body (distal), such as the muscles of the hands or feet. The myopathy may be especially noticeable during exercise (exercise intolerance).
An abnormality of the functioning of the vestibular apparatus.
A type of gait ataxia displaying progression of clinical severity.
Square wave jerks are saccadic eye movements which, when recorded with open eyes are considered to be a pathological sign, caused by fixation instability, and pointing to a central neurological lesion.
A genetically heterogeneous condition, typically inherited in an autosomal recessive fashion, characterized by coenzyme Q10 deficiency.
A tendency to fall or the inability to keep oneself from falling; imbalance. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, Use of the retropulsion test includes a rapid balance perturbation in the backward direction, and the number of balance correcting steps (or total absence thereof) is used to rate the degree of postural instability. Healthy subjects correct such perturbations with either one or two large steps, or without taking any steps, hinging rapidly at the hips while swinging the arms forward as a counterweight. In patients with balance impairment, balance correcting steps are often too small, forcing patients to take more than two steps. Taking three or more steps is generally considered to be abnormal, and taking more than five steps is regarded as being clearly abnormal. Markedly affected patients continue to step backward without ever regaining their balance and must be caught by the examiner (this would be called true retropulsion). Even more severely affected patients fail to correct entirely, and fall backward like a pushed toy soldier, without taking any corrective steps.
Inflammation of the liver due to infection with enterovirus.
Heterotaxy Heterotaxy ('heter' meaning 'other' and 'taxy' meaning 'arrangement'), or situs ambiguus, is a developmental condition characterized by randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another (Srivastava, 1997). Heterotaxy is a clinically and genetically heterogeneous disorder. Multiple Types of Congenital Heart Defects Congenital heart defects (CHTD) are among the most common congenital defects, occurring with an incidence of 8/1,000 live births. The etiology of CHTD is complex, with contributions from environmental exposure, chromosomal abnormalities, and gene defects. Some patients with CHTD also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions (summary by van de Meerakker et al., 2011). Reviews Obler et al. (2008) reviewed published cases of double-outlet right ventricle and discussed etiology and associations. Genetic Heterogeneity of Visceral Heterotaxy See also HTX2 (605376), caused by mutation in the CFC1 gene (605194) on chromosome 2q21; HTX3 (606325), which maps to chromosome 6q21; HTX4 (613751), caused by mutation in the ACVR2B gene (602730) on chromosome 3p22; HTX5 (270100), caused by mutation in the NODAL gene (601265) on chromosome 10q22; HTX6 (614779), caused by mutation in the CCDC11 gene (614759) on chromosome 18q21; HTX7 (616749), caused by mutation in the MMP21 gene (608416) on chromosome 10q26; and HTX8 (617205), caused by mutation in the PKD1L1 gene (609721) on chromosome 7p12. Genetic Heterogeneity of Multiple Types of Congenital Heart Defects An X-linked form of CHTD, CHTD1, is caused by mutation in the ZIC3 gene on chromosome Xq26. CHTD2 (614980) is caused by mutation in the TAB2 gene (605101) on chromosome 6q25. A form of nonsyndromic congenital heart defects associated with cardiac rhythm and conduction disturbances (CHTD3; 614954) has been mapped to chromosome 9q31. CHTD4 (615779) is caused by mutation in the NR2F2 gene (107773) on chromosome 15q26. CHTD5 (617912) is caused by mutation in the GATA5 gene (611496) on chromosome 20q13. CHTD6 (613854) is caused by mutation in the GDF1 gene (602880) on chromosome 19p13.
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory response resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis); granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. CGD may present any time from infancy to late adulthood; however, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival.
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection. [HPO:probinson]
Increased susceptibility to fungal infections, as manifested by multiple episodes of fungal infection.
An absence of the phase of elevated metabolic activity, during which oxygen consumption increases, that occurs in neutrophils, monocytes, and macrophages shortly after phagocytosing material. An enhanced uptake of oxygen leads to the production, by an NADH dependent system, of hydrogen peroxide (H2O2), superoxide anions and hydroxyl radicals, which play a part in microbiocidal activity.
Habib et al. (1973) recognized 2 morphologic classes for the glomerular changes seen in patients with mesangiocapillary (membranoproliferative) glomerulonephritis (MPGN). Type I is characterized by double contour appearance of the capillary walls due to mesangial cell interposition, with nonargyrophilic subendothelial deposits which are finely granular on electron microscopy. Type II is characterized by linear dense deposits within the basement membrane and only rare double contours. These 2 types appear to be distinct with no conversion of one type to another on serial biopsy. Strife et al. (1977) described a third variety in which there are not only subendothelial deposits but also numerous subepithelial and intramembranous deposits, associated with replication of the lamina densa and frequently disruption of the whole basement membrane.
A marked tapering of the lower face to the chin.
An abnormal increase in the size of the foramen magnum.
Anterior mislocalization of the dens of the axis.
Developmental hypoplasia of the clitoris.
Developmental defect resulting in congenital absence of the middle portion of the clavicle.
Underdevelopment of the middle portion of the clavicle.
The presence of a notch in the margin of the ala nasi.
Abnormally short finger associated with developmental hypoplasia.
An abnormal distribution of eyebrow hair growth in the medial direction.
Elevated ratio between the upper and the lower segment of the body, where the lower segment is defined as the length between the top of pubic symphysis to floor, and the upper segment is defined as the top of head to top of pubic symphysis.
Increased volume of the earlobe, that is, abnormally prominent ear lobules.
The ability of the finger joints to move beyond their normal range of motion.
Subjective impression of increased softness upon palpitation of the skin. [HPO:probinson]
Bluish-grey, spongy nodules associated with scars over pressure points and easily traumatized areas like the elbows and knees.
Increased pigmentation of the skin in the region surrounding the orbit of the eye.
Absence or developmental hypoplasia of the eccrine sweat glands.
Leukoplakia is a precancerous dermatosis of mucous membranes analogous Leukoplakia is basically a chronic inflammatory hypertrophy in which anaplasia and malignant dyskeratosis may develop and subsequently advance to an invasive squamous cell cancer. The clinical diagnosis of primary anal leukoplakia is indicated by single or multiple slightly raised,irregular, marginated, grayish-white keratinized' patches in the anal canal. Tissue biopsy is necessary for confirmation.
Episodes of fever for which no infectious cause can be identified.
Altered immune function characterized by lymphoid proliferation, immune activation, and excessive autoreactivity often leading to autoimmune/inflammatory complications.
An exceedingly rare, benign, congenital, corneal tumor characterized by bilateral opacification of the cornea with superficial grayish layers and irregular raised whitish plaques, as well as fine blood vessels covering the central cornea, and intact peripheral corneal borders. No other ocular or systemic abnormality is noted. The pattern of inheritance described in the affected family is consistent with X-linked transmission.
DFNX1 nonsyndromic hearing loss and deafness is part of the spectrum of PRPS1-related disorders. Hearing loss in hemizygous males is bilateral, sensorineural, and moderate to profound; prelingual or postlingual in onset; and progressive or non-progressive. The audiogram shape is variable. Hearing in female carriers can be normal or abnormal.
DFNX2, also known as DFN3, is an X-linked recessive disorder characterized by progressive conductive and sensorineural hearing loss and a pathognomonic temporal bone deformity that includes dilatation of the inner auditory canal and a fistulous connection between the internal auditory canal and the cochlear basal turn, resulting in a perilymphatic fluid 'gusher' during stapes surgery (summary by de Kok et al., 1995 and Song et al., 2010). See also choroideremia, deafness, and mental retardation (303110), a contiguous gene deletion syndrome involving the POU3F4 and CHM (300390) genes on Xq21; isolated choroideremia (303100) is caused by mutation in the CHM gene.
This syndrome is characterised by the association of congenital mixed hearing loss with perilymphatic gusher, hypogonadism and abnormal behaviour. It has been described in five related males. Inheritance appears to be X-linked recessive and a microdeletion, encompassing the POU3F4 gene (DFN3 locus), was detected in one of the patients leading to the suggestion that deafness hypogonadism is a contiguous gene deletion syndrome.
A benign growth the projects outward from the bone surface of the pelvis. Exostoses are capped by cartilage, and arise from a bone that develops from cartilage.
An abnormal vertical orientation of the clivus (which normally forms a kind of slope from the sella turcica down to the region of the foramen magnum).
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Absent or nearly absent fibula. (Does not include aplastic)
Displacement of the 2nd finger towards the radial side.
The presence of a fifth metatarsal bone that has not undergone ossification at an age when ossification is usually visible.
Underdevelopment of the breast on one side only.
Shortening of a leg affecting only one side.
Presence of a cutaneous membrane (flap) in the armpit.
Complete or partial merging of adjacent ribs.
Punched out lesions in the pigmented layer of the retina.
In the orthopedic and radiological literature, sagittally cleft vertebra is generally known as a butterfly vertebra.
Congenital synostosis between two or more adjacent vertebrae (partial or complete fusion of adjacent vertabral bodies).
X-linked cone-rod dystrophy is a rare, progressive visual disorder primarily affecting cone photoreceptors (Demirci et al., 2002). Affected individuals, essentially all of whom are males, present with decreased visual acuity, myopia, photophobia, abnormal color vision, full peripheral visual fields, decreased photopic electroretinographic responses, and granularity of the macular retinal pigment epithelium. The degree of rod photoreceptor involvement is variable, with increasing degeneration. Although penetrance appears to be nearly 100%, there is variable expressivity with respect to age at onset, severity of symptoms, and findings (Hong et al., 1994). Genetic Heterogeneity of X-linked Cone-Rod Dystrophy Additional forms of X-linked cone-rod dystrophy include CORDX2 (300085), mapped to chromosome Xq27, and CORDX3 (300476), caused by mutation in the CACNA1F gene (300110) on chromosome Xp11.23. For a discussion of autosomal forms of cone-rod dystrophy, see CORD2 (120970).
Abnormally increased thickness of the nasal septum.
Increased spaces (diastemata) between most of the teeth in the same dental arch.
The ability of a joint to move beyond its normal range of motion.
Rounding and broadening of the tufts of the distal phalanges.
When viewed on end (with the finger tip pointing toward the examiner's eye) the curve of the fingernail forms a tighter curve of convexity.
An X-linked retinal dystrophy, characterised by choroideraemia, causing in affected males progressive nyctalopia and eventual central blindness. Obesity, moderate intellectual disability and congenital mixed (sensorineural and conductive) deafness are also observed. Female carriers show typical retinal changes indicative of the choroideraemia carrier state.
Point-shaped (punctate) calcifications affecting the carpal bones.
The presence of abnormal punctate (speckled, dot-like) calcifications in one or more tarsal bones.
X-linked chondrodysplasia punctata 1 (CDPX1), a congenital disorder of bone and cartilage development, is caused by a deficiency of the Golgi enzyme arylsulfatase E (ARSE). It is characterized by chondrodysplasia punctata (stippled epiphyses), brachytelephalangy (shortening of the distal phalanges), and nasomaxillary hypoplasia. Although most affected males have minimal morbidity and skeletal findings that improve by adulthood, some have significant medical problems including respiratory compromise, cervical spine stenosis and instability, mixed conductive and sensorineural hearing loss, and intellectual disability.
Reduced superior to inferior length of the nasal septum.
A multiple congenital anomalies syndrome with manifestations of cleft palate, ocular coloboma, hypospadias, mixed conductive-sensorineural hearing loss, short stature and radio-ulnar synostosis. To date, 4 cases have been described in the literature. These manifestations overlap with those of CHARGE syndrome, however, in contrast to CHARGE syndrome, patients with Abruzzo-Erikson syndrome do not show intellectual disability, choanal atresia or genital hypoplasia. Inherited in an X-linked recessive manner, with a carrier female having a 50% chance of transmitting the mutation to her offspring.
Catel-Manzke syndrome is characterized by the Pierre Robin anomaly, which comprises cleft palate, glossoptosis, and micrognathia, and a unique form of bilateral hyperphalangy in which there is an accessory bone inserted between the second metacarpal and its corresponding proximal phalanx, resulting in radial deviation of the index finger (summary by Manzke et al., 2008).
Displacement of the 2nd (index) finger towards the ulnar side.
Increased width of a non-thumb digit of the hand.
Recurrent infections at an early age with improvement in later childhood.
An intermittent (discontinuous) form of lactic acidemia.
An extremely rare multiple congenital abnormality syndrome that has characteristics of microcephaly, malar hypoplasia with downslanting palpebral fissures, highly arched palate, apparently low-set and protruding ears, micrognathia, short stature, bilateral hearing loss, and learning disability. Occasionally, additional features have been observed such as bilateral cryptorchidism, cardiac valvular lesions, body asymmetry, and pectus excavatum.
An abnormal narrowing of the cervical spinal canal.
Spinocerebellar ataxia, X-linked, type 4 has characteristics of ataxia, pyramidal tract signs and adult-onset dementia. It has been described in three generations of one large family. The disease manifests during early childhood with delayed walking and tremor. The pyramidal signs appear progressively and by adulthood memory problems and dementia gradually become apparent. Transmission is X-linked but the causative gene has not yet been identified. The disease is usually fatal during the sixth decade of life.
X-linked infantile spinal muscular atrophy (XL-SMA) is characterized by congenital hypotonia and areflexia and evidence of degeneration and loss of anterior horn cells (i.e., lower motor neurons) in the spinal cord and brain stem. Often congenital contractures and/or fractures are present. Intellect is normal. Life span is shortened because of progressive ventilatory insufficiency resulting from chest muscle involvement.
This syndrome is a form of spinocerebellar degeneration with onset in infancy of hypotonia, ataxia, sensorineural deafness, developmental delay, esotropia and optic atrophy and by a progressive course leading to death in childhood. It has been described one family with at least six affected males from five different sibships (connected through carrier females). It is transmitted as an X-linked recessive trait.
Death within the first 24 months of life.
The dividing wall between left and right sides of the heart, thickens and bulges into the left ventricle.
X-linked sideroblastic anemia and ataxia (XLSA/A) is characterized by moderate anemia and early-onset spinocerebellar syndrome in males, manifest primarily as delayed walking, ataxia evident in early childhood, dysmetria, and dysdiadochokinesis. When present the intention tremor is mild and the dysarthria is mild to moderately severe. The ataxia has been described to be either non-progressive or slowly progressive. Upper motor neuron (UMN) signs in the legs, manifest by brisk deep tendon reflexes, unsustained ankle clonus, and equivocal or extensor plantar responses, are present in some males. Need for crutches or a wheelchair has been reported. Strabismus is seen in some males. Nystagmus and hypometric saccades may occur. Mild learning disability and depression are seen. The moderate hypochromic and microcytic anemia does not cause symptoms. Carrier (heterozygous) females have a normal neurologic examination and may show mild hematologic abnormalities.
X-linked reticulate pigmentary disorder shows more severe manifestations in hemizygous males compared to heterozygous females. Affected males have early onset of recurrent respiratory infections and failure to thrive resulting from inflammatory gastroenteritis or colitis. Patients also show reticular pigmentation abnormalities of the skin and may develop corneal scarring. Carrier females may be unaffected or have only pigmentary abnormalities along the lines of Blaschko (summary by Starokadomskyy et al., 2016).
Amelogenesis imperfecta is an inherited defect of dental enamel formation that shows both clinical and genetic heterogeneity. In the hypoplastic type of AI, the enamel is of normal hardness but does not develop to normal thickness. The thinness of the enamel makes the teeth appear small. Radiographically, enamel contrasts normally from dentin. The surface of the enamel can vary, showing smooth, rough, pitted, or local forms (Witkop, 1988).
Syndrome with characteristics of congenital nerve deafness and piebaldness without ocular albinism. Transmission is X-linked with affected males presenting with profound sensorineural deafness and severe pigmentary abnormalities of the skin and carrier females presenting with variable hearing impairment without any pigmentary changes. The causative gene has been mapped to Xq26.3-q27.1.
Ocular albinism is a genetic condition that primarily affects the eyes. This condition reduces the coloring (pigmentation) of the iris, which is the colored part of the eye, and the retina, which is the light-sensitive tissue at the back of the eye. Pigmentation in the eye is essential for normal vision.Ocular albinism is characterized by severely impaired sharpness of vision (visual acuity) and problems with combining vision from both eyes to perceive depth (stereoscopic vision). Although the vision loss is permanent, it does not worsen over time. Other eye abnormalities associated with this condition include rapid, involuntary eye movements (nystagmus); eyes that do not look in the same direction (strabismus); and increased sensitivity to light (photophobia). Many affected individuals also have abnormalities involving the optic nerves, which carry visual information from the eye to the brain.Unlike some other forms of albinism, ocular albinism does not significantly affect the color of the skin and hair. People with this condition may have a somewhat lighter complexion than other members of their family, but these differences are usually minor.The most common form of ocular albinism is known as the Nettleship-Falls type or type 1. Other forms of ocular albinism are much rarer and may be associated with additional signs and symptoms, such as hearing loss.
X-linked lymphoproliferative disease (XLP) has two recognizable subtypes, XLP1 and XLP2. XLP1 is characterized predominantly by one of three commonly recognized phenotypes: Inappropriate immune response to Epstein-Barr virus (EBV) infection leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis. Dysgammaglobulinemia. Lymphoproliferative disease (malignant lymphoma). XLP2 is most often characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease. HLH resulting from EBV infection is associated with an unregulated and exaggerated immune response with widespread proliferation of cytotoxic T cells, EBV-infected B cells, and macrophages. Dysgammaglobulinemia is typically hypogammaglobulinemia of one or more immunoglobulin subclasses. The malignant lymphomas are typically B-cell lymphomas, non-Hodgkin type, often extranodal, and in particular involving the intestine.
X-linked deafness-5 is a neurologic disorder characterized by childhood onset of auditory neuropathy and later onset of distal sensory impairment affecting the peripheral nervous system (summary by Zong et al., 2015).
Unusual prominence of the median palatal raphe, which is the ridge formed by the fusion of the two plates of the skull that form the hard palate.
Increased depth of the median tongue furrow.
Increased distance between the maxillary central permanent incisor tooth.
Decreased size of the maxillary permanent incisor.
Idiopathic short stature is usually defined as a height below the third percentile for chronological age or minus 2 standard deviations (SD) of national height standards in the absence of specific causative disorders (Rao et al., 1997). For a discussion of genetic heterogeneity of quantitative trait loci for stature, see STQTL1 (606255).
FG syndrome is a genetic condition that affects many parts of the body and occurs almost exclusively in males. ""FG"" represents the surname initials of the first family diagnosed with the disorder.FG syndrome affects intelligence and behavior. Almost everyone with the condition has intellectual disability, which ranges from mild to severe. Affected individuals tend to be friendly, inquisitive, and hyperactive, with a short attention span. Compared to people with other forms of intellectual disability, their socialization and daily living skills are strong, while verbal communication and language skills tend to be weaker.The physical features of FG syndrome include weak muscle tone (hypotonia), broad thumbs, and wide first (big) toes. Abnormalities of the tissue connecting the left and right halves of the brain (the corpus callosum) are also common. Most affected individuals have constipation, and many have abnormalities of the anus such as an obstruction of the anal opening (imperforate anus). People with FG syndrome also tend to have a distinctive facial appearance including small, underdeveloped ears; a tall, prominent forehead; and outside corners of the eyes that point downward (down-slanting palpebral fissures).Additional features seen in some people with FG syndrome include widely set eyes (hypertelorism), an upswept frontal hairline, and a large head compared to body size (relative macrocephaly). Other health problems have also been reported, including heart defects, seizures, undescended testes (cryptorchidism) in males, and a soft out-pouching in the lower abdomen (an inguinal hernia).
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period and affecting the entire musculature.
Presence of myoglobin in the urine following exercise. [HPO:probinson]
X-linked recessive hypophosphatemic rickets is a form of X-linked hypercalciuric nephrolithiasis, which comprises a group of disorders characterized by proximal renal tubular reabsorptive failure, hypercalciuria, nephrocalcinosis, and renal insufficiency. These disorders have also been referred to as the 'Dent disease complex' (Scheinman, 1998; Gambaro et al., 2004). For a general discussion of Dent disease, see 300009.
High urine phosphate in the presence of hypophosphatemia.
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. The syndrome manifests as an inability to excrete a free water load, with inappropriately concentrated urine and resultant hyponatremia, hypoosmolality, and natriuresis. SIADH occurs in a setting of normal blood volume, without evidence of renal disease or deficiency of thyroxine or cortisol. Although usually transient, SIADH may be chronic; it is often associated with drug use or a lesion in the central nervous system or lung. When the cardinal features of SIADH were defined by Bartter and Schwartz (1967), levels of AVP could not be measured. Subsequently, radioimmunoassays revealed that SIADH is usually associated with measurably elevated serum levels of AVP. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is characterized by a clinical picture similar to SIADH, but is associated with undetectable levels of AVP (Feldman et al., 2005).
An decreased level of renin (PRO:000013883) in the blood.
Ehlers-Danlos syndrome (EDS) with periventricular heterotopia is a newly described variant of EDS.
The presence of a forehead that is abnormally small.
Reduced muscle tone of a muscle that is innervated by the facial nerve (the seventh cranial nerve).
The presence of an abnormally prominent antihelix.
Any deviation from the normal motor coordination of the eyes that allows for bilateral fixation on a single object.
Hypergonadotropic ovarian failure is a heterogeneous disorder that, in the most severe forms, is a result of ovarian dysgenesis. Ovarian dysgenesis accounts for about half the cases of primary amenorrhea (Timmreck and Reindollar, 2003). Most cases are associated with major X chromosome abnormalities. Accordingly, genetic studies have identified several loci at Xq and Xp11.2-p.22.1 whose functions are relevant for ovarian development (Zinn et al., 1998; Simpson and Rajkovic, 1999; Marozzi et al., 2000).
Asperger syndrome is considered to be a form of childhood autism (see, e.g., 209850). The DSM-IV (American Psychiatric Association, 1994) specifies several diagnostic criteria for Asperger syndrome, which has many of the same features as autism. In general, patients with Asperger syndrome and autism exhibit qualitative impairment in social interaction, as manifest by impairment in the use of nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures, failure to develop appropriate peer relationships, and lack of social sharing or reciprocity. Patients also exhibit restricted, repetitive and stereotyped patterns of behavior, interests, and activities, including abnormal preoccupation with certain activities and inflexible adherence to routines or rituals. Asperger syndrome is primarily distinguished from autism by the higher cognitive abilities and a more normal and timely development of language and communicative phrases. Gillberg et al. (2001) described the development of the Asperger syndrome (and high-functioning autism) Diagnostic Interview (ASDI), which they claimed has a strong validity in the diagnosis of the disorder. For a discussion of genetic heterogeneity of Asperger syndrome, see 608638.
Cone-rod dystrophy is a retinal disorder with predominantly cone involvement. Rod impairment may occur at the same time as the cone impairment or appear later. Patients with CORD usually have reduced visual acuity, photophobia, and color vision defects (summary by Huang et al., 2013). For a discussion of genetic heterogeneity of X-linked cone-rod dystrophy, see 304020.
Laterally protruding ear that lacks antihelical folding (including absence of inferior and superior crura).
Mental retardation, bilateral congenital hip luxation, and short stature associated the presence of a variant of glucose-6-phosphate dehydrogenase.
CASK-related disorders include a spectrum of phenotypes in both females and males. The two main types of clinical presentation are: Microcephaly with pontine and cerebellar hypoplasia (MICPCH), generally associated with pathogenic loss-of-function variants in CASK; and X-linked intellectual disability (XLID) with or without nystagmus, generally associated with hypomorphic CASK pathogenic variants. MICPCH is typically seen in females with moderate to severe intellectual disability, progressive microcephaly with or without ophthalmologic anomalies, and sensorineural hearing loss. To date a total of 53 females with MICPCH have been reported, the eldest of whom is 21 years old. Most are able to sit independently; 20%-25% attain the ability to walk; language is nearly absent in most. Neurologic features may include axial hypotonia, hypertonia/spasticity of the extremities, and dystonia or other movement disorders. Nearly 40% have seizures. Behaviors may include sleep disturbances, hand stereotypies, and self-biting. To date, only seven males have been reported with the severe phenotype. The under-representation in this cohort is likely to be a consequence of early male lethality. These males typically present with intellectual disability and MICPCH, or early-infantile epileptic encephalopathy (Ohtahara syndrome, West syndrome, or early myoclonic epilepsy). In individuals and families with milder (i.e., hypomorphic) pathogenic variants, the clinical phenotype is usually that of X-linked intellectual disability (XLID) with or without nystagmus and additional clinical features. More than 24 males and nine females have been reported. The males have mild to severe intellectual disability, with or without nystagmus and other ocular features. Females are typically normal, with some displaying mild intellectual disability with or without ocular features.
An increased susceptibility to bacterial meningitis as manifested by a medical history of recurrent episodes of bacterial meningitis.
Polymicrogyria (PMG) is a malformation of cortical development in which the brain surface is irregular and the normal gyral pattern replaced by multiple small, partly fused gyri separated by shallow sulci. Microscopic examination shows a simplified 4-layered or unlayered cortex. Several patterns of PMG, including bilateral frontal, bilateral perisylvian, and bilateral mesial occipital PMG, have been described on the basis of their topographic distribution. All but the perisylvian form appear to be rare. Bilateral perisylvian PMG (BPP) often results in a typical clinical syndrome that is manifested by mild mental retardation, epilepsy, and pseudobulbar palsy, which causes difficulties with expressive speech and feeding (Kuzniecky et al., 1993). PMG may be a feature of other conditions as well (see, e.g., 300643).
Abnormally increased density of craniofacial bone tissue.
Dyserythropoietic anemia and thrombocytopenia is a condition that affects blood cells and primarily occurs in males. A main feature of this condition is a type of anemia called dyserythropoietic anemia, which is characterized by a shortage of red blood cells. The term ""dyserythropoietic"" refers to the abnormal red blood cell formation that occurs in this condition. In affected individuals, immature red blood cells are unusually shaped and cannot develop into functional mature cells, leading to a shortage of healthy red blood cells. People with dyserythropoietic anemia and thrombocytopenia can have another blood disorder characterized by a reduced level of circulating platelets (thrombocytopenia). Platelets are cell fragments that normally assist with blood clotting. Thrombocytopenia can cause easy bruising and abnormal bleeding. While people with dyserythropoietic anemia and thrombocytopenia can have signs and symptoms of both blood disorders, some are primarily affected by anemia, while others are more affected by thrombocytopenia.The most severe cases of dyserythropoietic anemia and thrombocytopenia are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. For many others, the signs and symptoms of dyserythropoietic anemia and thrombocytopenia begin in infancy. People with this condition experience prolonged bleeding or bruising after minor trauma or even in the absence of injury (spontaneous bleeding). Anemia can cause pale skin, weakness, and fatigue. Severe anemia may create a need for frequent blood transfusions to replenish the supply of red blood cells; however, repeated blood transfusions over many years can cause health problems such as excess iron in the blood. People with dyserythropoietic anemia and thrombocytopenia may also have a shortage of white blood cells (neutropenia), which can make them prone to recurrent infections. Additionally, they may have an enlarged spleen (splenomegaly). The severity of these abnormalities varies among affected individuals.Some people with dyserythropoietic anemia and thrombocytopenia have additional blood disorders such as beta thalassemia or congenital erythropoietic porphyria. Beta thalassemia is a condition that reduces the production of hemoglobin, which is the iron-containing protein in red blood cells that carries oxygen. A decrease in hemoglobin can lead to a shortage of oxygen in cells and tissues throughout the body. Congenital erythropoietic porphyria is another disorder that impairs hemoglobin production. People with congenital erythropoietic porphyria are also very sensitive to sunlight, and areas of skin exposed to the sun can become fragile and blistered.
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
This form of syndromic X-linked mental retardation is characterized primarily by short stature, hypogonadism, and abnormal gait, with other more variable features such as speech delay, prominent lower lip, and tremor (Cabezas et al., 2000).
Ocular coloboma is a developmental defect of the eye resulting from abnormal or incomplete fusion of the optic fissure. The defect can be unilateral or bilateral and can involve the cornea, iris, ciliary body, lens, choroid, retina, and/or optic nerves. Clinically, coloboma is often associated with microphthalmia or clinical anophthalmia and can occur as part of complex malformation syndromes (summary by Wang et al., 2012). Genetic Heterogeneity of Isolated Microphthalmia With Coloboma Isolated colobomatous microphthalmia-1 (MCOPCB1) has been mapped to the X chromosome. MCOPCB2 (605738) has been mapped to chromosome 15q12-q15. MCOPCB3 (610092) is caused by mutation in the CHX10 gene (142993) on chromosome 14q24. MCOPCB5 (611638) is caused by mutation in the SHH gene (600725) on chromosome 7q36. MCOPCB6 (613703) is caused by mutation in the GDF3 gene (606522) on chromosome 12p13.1. MCOPCB7 (614497) is caused by mutation in the ABCB6 gene (605452) on chromosome 2q36. MCOPCB8 (see 601186) is caused by mutation in the STRA6 gene (601745) on chromosome 15q24. MCOPCB9 (615145) is caused by mutation in the TENM3 gene (610083) on chromosome 4q35. See 251505 for a discussion of MCOPCB4.
Irregular distribution of the teeth along the dental arch, i.e., and irregular spatial pattern of teeth.
Although the phenotypic spectrum and severity of FG syndrome is wide, the cardinal features include congenital hypotonia, delayed speech development, relative macrocephaly, dysmorphic facies, and anal anomalies or severe constipation (Unger et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of FG syndrome, see FGS1 (305450).
Immunodeficiency-61 (IMD61) is an X-linked recessive primary immunodeficiency characterized by onset of recurrent infections in early childhood due to impaired antibody production. Affected individuals have normal numbers of circulating B and T cells, but B cells have an intrinsic defect in antibody production (summary by Keller et al., 2018). For a general phenotypic description of X-linked agammaglobulinemia, see AGMX1 (300755).
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
Ectodermal dysplasia with immunodeficiency-1 is an X-linked recessive disorder characterized by variable ectodermal features, but most often including hypo/anhidrosis, and various immunologic and infectious phenotypes of differing severity. Genetic Heterogeneity of Ectodermal Dysplasia and Immune Deficiency Also see EDAID2 (612132), caused by mutation in the NFKBIA gene (164008).
IMAGe syndrome is an acronym for the major findings of intrauterine growth restriction (IUGR), metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary abnormalities (in males). Findings reported in individuals with a clinical and/or molecular diagnosis include: IUGR; Some type of skeletal abnormality (most commonly delayed bone age and short stature and, occasionally, metaphyseal and epiphyseal dysplasia of varying severity); Adrenal insufficiency often presenting in the first month of life as an adrenal crisis or rarely later in childhood with failure to thrive and recurrent vomiting; Genital abnormalities in males (cryptorchidism, micropenis, and hypospadias) but not in females. Hypotonia and developmental delay are reported in some; cognitive outcome appears to be normal in the majority.
Coarse facial features reminiscent of those of a boxer.
Severe hypertrophy (increase in size) of muscle cells.
The development of Pes cavus that is progressive with age.
Multinodular goiter is a common disorder characterized by nodular enlargement of the thyroid gland. It occurs with a female:male ratio of 5:1 (summary by Capon et al., 2000). For additional phenotypic information and a discussion of genetic heterogeneity of multinodular goiter, see MNG1 (138800).
An extremely rare genetic endocrine disease with characteristics of primary adrenal insufficiency, dystrophic myopathy, hepatic steatosis, severe psychomotor delay, megalocornea, failure to thrive, chronic constipation, and terminal bladder ectasia which can lead to death. There have been no further descriptions in the literature since 1982.
Spastic paraplegias (SPGs) are a genetically heterogeneous group of neurologic disorders characterized by progressive weakness and spasticity of the legs. Complicated SPGs are accompanied by additional neurologic symptoms such as cerebellar ataxia, sensory loss, mental retardation, nystagmus, and optic atrophy (summary by Steinmuller et al., 1997). A locus for spastic paraplegia-16 has been mapped to Xq11.2-q23 (Steinmuller et al., 1997). For a discussion of genetic heterogeneity of X-linked spastic paraplegia, see 303350.
X-linked intellectual disability, Siderius type is a condition characterized by mild to moderate intellectual disability that affects only males. Affected boys often have delayed development of motor skills such as walking, and their speech may be delayed.Individuals with X-linked intellectual disability, Siderius type frequently also have an opening in the lip (cleft lip) with an opening in the roof of the mouth (cleft palate). A cleft can occur on one or both sides of the upper lip.Some boys and men with this condition have distinctive facial features, including a long face, a sloping forehead, a broad nasal bridge, a prominent bone in the lower forehead (supraorbital ridge), and outside corners of the eyes that point upward (upslanting palpebral fissures). Affected individuals may also have low-set ears and large hands.
The MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by infantile hypotonia, delayed psychomotor development leading to severe intellectual disability, poor speech development, progressive spasticity, recurrent respiratory infections (in ~75% of affected individuals), and seizures (in ~50%). MECP2 duplication syndrome is 100% penetrant in males. Occasionally females have been described with a MECP2 duplication and related clinical findings, often associated with concomitant X-chromosomal abnormalities that prevent inactivation of the duplicated region. Generalized tonic-clonic seizures are most often observed; atonic seizures and absence seizures have also been described. One third of affected males are never able to walk independently. Almost 50% of affected males die before age 25 years, presumably from complications of recurrent infection and/or neurologic deterioration. In addition to the core features, autistic behaviors and gastrointestinal dysfunction have been observed in several affected boys. Although interfamilial phenotypic variability is observed, severity is usually consistent within families.
Roifman syndrome is a multisystem disorder characterized by growth retardation, spondyloepiphyseal dysplasia, retinal dystrophy, distinctive facial dysmorphism, and immunodeficiency (summary by de Vries et al., 2006).
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs with onset in infancy.
Terminal osseous dysplasia is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma during infancy (Sun et al., 2010).
Generalized tonic-clonic seizures that are triggered by flashing or flickering light.
Hoyeraal-Hreidarsson syndrome is a multisystem disorder affecting males and is characterized by aplastic anemia, immunodeficiency, microcephaly, cerebellar hypoplasia, and growth retardation.
The term progressive intellectual disability should be used if intelligence decreases/deteriorates over time.
An increase in size of the anatomic space between the arachnoid membrane and pia mater.
A cone-shaped deformity of the proximal epiphysis of the femur.
Classic Hodgkin lymphoma is a malignancy of B-cell origin in which the neoplastic cells, known as 'Reed-Sternberg' (RS) cells, are characteristically binucleated (summary by Salipante et al., 2009). See also 236000.
X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females may be unaffected or have a milder phenotype (Bonneau et al., 2002). LISX2 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1; 308350) to syndromic (309510) and nonsyndromic (300419) mental retardation (Kato et al., 2004; Wallerstein et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Simpson-Golabi-Behmel syndrome is a condition that affects many parts of the body and occurs primarily in males. This condition is classified as an overgrowth syndrome, which means that affected infants are considerably larger than normal at birth (macrosomia) and continue to grow and gain weight at an unusual rate. The other signs and symptoms of Simpson-Golabi-Behmel syndrome vary widely. People with mild cases often live into adulthood.People with Simpson-Golabi-Behmel syndrome have distinctive facial features including widely spaced eyes (ocular hypertelorism), an unusually large mouth (macrostomia), a large tongue (macroglossia) that may have a deep groove or furrow down the middle, a broad nose with an upturned tip, and abnormalities affecting the roof of the mouth (the palate). The facial features are often described as ""coarse"" in older children and adults with this condition.Other features of Simpson-Golabi-Behmel syndrome involve the chest and abdomen. Affected infants may be born with one or more extra nipples, an abnormal opening in the muscle covering the abdomen (diastasis recti), a soft out-pouching around the belly-button (an umbilical hernia), or a hole in the diaphragm (a diaphragmatic hernia) that allows the stomach and intestines to move into the chest and crowd the developing heart and lungs.Simpson-Golabi-Behmel syndrome can also cause heart defects, malformed or abnormally large kidneys, an enlarged liver and spleen (hepatosplenomegaly), and skeletal abnormalities. Additionally, the syndrome can affect the development of the gastrointestinal system, urinary system, and genitalia. Some people with this condition have mild to severe intellectual disability, while others have normal intelligence.About 10 percent of people with Simpson-Golabi-Behmel syndrome develop cancerous or noncancerous tumors in early childhood. The most common tumors are a rare form of kidney cancer called Wilms tumor and a cancerous tumor called a neuroblastoma that arises from developing nerve cells.
Developmental hypoplasia of the adrenal glands.
This syndrome has characteristics of the association of Alport syndrome, midface hypoplasia, intellectual deficit and elliptocytosis. It has been described in two families. The syndrome is transmitted as an X-linked trait is caused by a contiguous gene deletion in Xq22.3 involving several genes including COL4A5, FACL4 and AMMECR1.
In mammals, the potential imbalance of gene expression for the two X chromosomes in females is resolved by inactivating one X in all the somatic tissues. In the embryo proper, the process of X inactivation is believed to be random between the maternal and paternal chromosomes. Thus, most females have mosaic expression of maternal and paternal alleles of X chromosome loci, with a contribution of about 50% from each chromosome. However, some females show a skewed ratio of X inactivation, which can be due to negative or positive selection, or to an underlying primary genetic process. Belmont (1996) observed familial clustering of females with highly skewed patterns of X inactivation and reviewed the genetic control of X inactivation. See also SXI1 (300087), due to mutation in the XIST gene (314670) on chromosome Xq13.2.
MEHMO syndrome has characteristics of severe intellectual deficit, epilepsy, microcephaly, hypogenitalism and obesity. Growth delay and diabetes are also present. To date, it has been described in seven boys, all of who died within the first two years of life. The causative gene has been located to the 21.1-22.13p region of the X chromosome and the syndrome appears to result from mitochondrial dysfunction.
Recurrent episodes of decreased concentration of glucose in the blood.
Baraitser-Winter cerebrofrontofacial (BWCFF) syndrome is a multiple congenital anomaly syndrome characterized by typical craniofacial features and intellectual disability (ID) that ranges from mild (usually in those with normal brain structure) to profound (typically in those with a neuronal migration defect). Many (but not all) affected individuals have iris or retinal coloboma, sensorineural deafness, and muscle wasting resulting in a peculiar stance with kyphosis, anteverted shoulders, and slightly flexed elbows and knees. Seizures, congenital heart defects, and renal malformations also are common.
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal (or neonatal) forms of Bartter syndrome (e.g., BARTS1, 601678) typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). Genetic Heterogeneity of Bartter Syndrome Antenatal Bartter syndrome type 1 (601678) is caused by loss-of-function mutations in the butmetanide-sensitive Na-K-2Cl cotransporter NKCC2 (SLC12A1; 600839). Antenatal Bartter syndrome type 2 (241200) is caused by loss-of-function mutations in the ATP-sensitive potassium channel ROMK (KCNJ1; 600359). One form of neonatal Bartter syndrome with sensorineural deafness, Bartter syndrome type 4A (602522), is caused by mutation in the BSND gene (606412). Another form of neonatal Bartter syndrome with sensorineural deafness, Bartter syndrome type 4B (613090), is caused by simultaneous mutation in both the CLCNKA (602024) and CLCNKB (602023) genes. Also see autosomal dominant hypocalcemia-1 with Bartter syndrome (601198), which is sometimes referred to as Bartter syndrome type 5 (Fremont and Chan, 2012), caused by mutation in the CASR gene (601199). See Gitelman syndrome (GTLMN; 263800), which is often referred to as a mild variant of Bartter syndrome, caused by mutation in the thiazide-sensitive sodium-chloride cotransporter SLC12A3 (600968).
An abnormally increased activity of the renin-angiotensin system, causing hypertension by a combination of volume excess and vasoconstrictor mechanisms.
A high concentration of one or more electrolytes in the urine in the presence of low serum concentrations of the electrolyte(s).
High urine potassium in the presence of hypokalemia.
An increased concentration of potassium(1+) in the urine.
An increased concentration of chloride in the urine.
Meckel syndrome is an autosomal recessive pre- or perinatal lethal malformation syndrome characterized by renal cystic dysplasia and variably associated features including developmental anomalies of the central nervous system (typically occipital encephalocele), hepatic ductal dysplasia and cysts, and postaxial polydactyly (summary by Smith et al., 2006). For a more complete phenotypic description and information on genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Idiopathic scoliosis is a structurally fixed lateral curvature of the spine with a rotatory component. There is at least a 10 degree curvature as demonstrated by upright spine roentgenograms by the Cobb method (Weinstein, 1994). For a discussion of genetic heterogeneity of isolated scoliosis, see 181800.
Focal cortical dysplasia type II (FCORD2), or focal cortical dysplasia of Taylor (FCDT), is a cerebral developmental malformation that results in a clinical phenotype of intractable epilepsy, usually requiring surgery. FCORD2 has been classified histologically into 2 subtypes: a type without balloon cells, known as type IIA, and a type with balloon cells, known as type IIB (Palmini et al., 2004). Affected individuals have refractory seizures, usually with onset in early childhood, and may have persistent intellectual disability. Most patients require neurosurgical resection of affected brain tissue to ameliorate seizure frequency and severity (summary by Moller et al., 2016).
An extremely rare inborn error of sterol biosynthesis with manifestations of facial dysmorphism, congenital anomalies (including limb and kidney anomalies), failure to thrive, developmental delay and liver disease. Only 4 cases have been reported in the literature to date. Lathosterolosis is due to mutations in the SC5D gene (11q23.3). A mutation in this gene leads to a deficiency in 3-beta-hydroxysteroid-delta-5-desaturase, which is necessary in the conversion of lathosterol into 7-dehydrocholesterol. This prevents the synthesis of cholesterol, which among other functions acts as a structural lipid, a precursor for bile acids and steroid hormones, and is necessary for the maturation of hedgehog morphogens during embryonic development. Inherited in an autosomal recessive manner.
The presence of a bilobed gallbladder, related to a duplication of the gallbladder primordium.
Height of the vermilion of the upper lip in the midline more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the upper lip in the frontal view (subjective).
A rare spondyloepimetaphyseal dysplasia with the clinical manifestations of coarse facies, short neck, short trunk dwarfism with barrel-shaped chest and rhizomelic limb shortening, as well as specific radiological features and normal intelligence.
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs.
The odontoid process, or dens, is a bony projection from the axis (C2) upward into the ring of the atlas (C1) at the top of the spine. During embryogenesis, the body of the odontoid derives from the centrum of the atlas and separates from the atlas, fusing with the superior portion of the axis. If the odontoid is hypoplastic or absent, the attachments for the apical and alar ligaments are missing, allowing for excessive rotation of the atlas, craniocervical instability, and possibly cord compression (summary by Stevens et al., 2009).
Delayed ossification of the femoral head.
There is normally one ossification center in the head of the femur. This term applies if there are multiple such centers.
An alteration of the normally smooth contour of the epiphysis leading to an irregular appearance.
A type of stenosis of the external auditory meatus in which the opening of the external auditory meatus appears as a vertical slit.
A malformation of the auricle of the ear.
An impaired ability of the eye to move in the outward direction (towards the side of the head).
Reduced ability to move the eye in the direction of the nose.
Developmental defect associated with absence of one or more metacarpal bones.
Underdevelopment of the thenar eminence with reduced palmar soft tissue mass surrounding the base of the thumb.
Underdevelopment of the pectoral muscle.
VPS13D movement disorder is a hyperkinetic movement disorder (dystonia, chorea, and/or ataxia) of variable age of onset that can be associated with developmental delay. Onset ranges from birth to adulthood. Individuals can present in childhood with motor delays and gait instability. Cognitive impairment ranging from mild intellectual disability to developmental delay has been reported, and several individuals have normal cognitive function. Individuals have also presented as young adults with gait difficulties caused by spastic ataxia or ataxia. In addition to gait ataxia, affected individuals had limb ataxia, dysarthria, and eye movement abnormalities (macro-saccadic oscillations, nystagmus, and saccadic pursuit). Additional features reported in some individuals include peripheral neuropathy and/or seizures. The disorder progresses to spastic ataxia or generalized dystonia, which can lead to loss of independent ambulation.
Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis (Laitinen et al., 2001; Illig and Wjst, 2002; Pillai et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of asthma, see 600807.
Caspase 8 deficiency is a syndrome of lymphadenopathy and splenomegaly, marginal elevation of 'double-negative T cells' (DNT; T-cell receptor alpha/beta+, CD4-/CD8-), defective FAS-induced apoptosis, and defective T-, B-, and natural killer (NK)-cell activation, with recurrent bacterial and viral infections (summary by Madkaikar et al., 2011).
An increased susceptibility to infections involving both the paranasal sinuses and the lungs, as manifested by a history of recurrent sinopulmonary infections.
Decreased or impaired activation of T cells in response to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
A reduced ability of a B cell to become activated, i.e., the change in morphology and behavior of
Spastic paraplegia 7 (SPG7) is characterized by insidiously progressive bilateral leg weakness and spasticity. Most affected individuals have decreased vibration sense and cerebellar signs. Onset is mostly in adulthood, although symptoms may start as early as age 11 years and as late as age 72 years. Additional features including ataxia (gait and limbs), spastic dysarthria, dysphagia, pale optic disks, ataxia, nystagmus, strabismus, ptosis, hearing loss, motor and sensory neuropathy, amyotrophy, scoliosis, pes cavus, and urinary sphincter disturbances may be observed.
Deterioration of the tissues of the lateral corticospinal tracts.
Spinocerebellar ataxia with axonal neuropathy (SCAN1) is characterized by late-childhood-onset slowly progressive cerebellar ataxia, followed by areflexia and signs of peripheral neuropathy. Gaze nystagmus and cerebellar dysarthria usually develop after the onset of ataxic gait. As the disease advances, pain and touch sensation become impaired in the hands and legs; vibration sense disappears in hands and lower thigh. Individuals with advanced disease develop a steppage gait and pes cavus and eventually become wheelchair dependent.
Celiac disease, also known as celiac sprue and gluten-sensitive enteropathy, is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins (summary by Farrell and Kelly, 2002). For additional information and a discussion of genetic heterogeneity of celiac disease, see 212750.
Amish lethal microcephaly is characterized by severe congenital microcephaly and highly elevated 2-ketoglutarate or lactic acidosis. The occipitofrontal circumference is typically more than two standard deviations (occasionally >6 SD) below the mean; anterior and posterior fontanels are closed at birth and facial features are distorted. The average life span of an affected infant is between five and six months among the Lancaster Amish, although an affected Amish-Mennonite child was reported to be living with severe developmental delay at age seven years.
This syndrome has characteristics of cloverleaf skull, limb anomalies, facial dysmorphism and multiple congenital anomalies. It has been described in three siblings from one family. Dysmorphic features include protruding forehead, hypertelorism, broad nasal bridge, wide anterior fontanelle and short philtrum, down turning mouth, micrognathia and low-set ears. The limbs show rhizomelic shortening. Additional malformations are not constant: omphalocele, bilateral microphthalmia, cataract, narrow chest, ambiguous genitalia, cardiac ventricular septal defect and agenesis of the corpus callosum. The condition seems to be inherited as an autosomal recessive trait. Prognosis is poor.
MDGDC5 is an autosomal recessive muscular dystrophy characterized by variable age at onset, normal cognition, and no structural brain changes (Brockington et al., 2001). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Mercuri et al., 2006). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
Muscle hypertrophy affecting the thighs.
Moyamoya disease is a progressive cerebral angiopathy characterized by bilateral internal carotid artery stenosis and abnormal collateral vessels. The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral angiogram. Affected individuals can develop transient ischemic attacks and/or cerebral infarction, and rupture of the collateral vessels can cause intracranial hemorrhage (summary by Kamada et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of moyamoya disease, see MYMY1 (252350).
Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course.
Anauxetic dysplasia is a disorder characterized by extremely short stature (dwarfism) and other skeletal abnormalities, an unusually large range of joint movement (hypermobility), dental problems, and distinctive facial features. Mild intellectual disability can also occur in this disorder.People with anauxetic dysplasia have dwarfism with unusually short limbs for their height (disproportionate short stature) beginning before birth. Dislocation of the bones at the top of the spine (atlantoaxial subluxation) can also occur in this disorder, and may cause pinching (compression) of the spinal cord. As a result, affected individuals may experience neurological symptoms including pain, tingling, numbness, coordination problems, weakness, and paralysis. In severe cases, the spinal cord compression may lead to paralysis of the muscles needed for breathing, which can be life-threatening during early childhood.Other skeletal abnormalities in anauxetic dysplasia include a barrel-shaped chest and a rounded upper back that also curves to the side (kyphoscoliosis). Without surgical correction, the kyphoscoliosis can constrict the lungs and cause difficulty breathing. People with anauxetic dysplasia can also have an exaggerated curvature of the lower back (hyperlordosis), dislocation of the hips, and soles of the feet that are rounded outward (rocker-bottom feet).Typical facial features in anauxetic dysplasia include closely spaced eyes (hypotelorism), a flat or sunken appearance of the middle of the face (midface hypoplasia), an unusually large tongue (macroglossia), and a protruding chin (prognathism). Affected individuals can also have fewer teeth than normal (hypodontia).
A partial dislocation of one or more intervertebral joints in the cervical vertebral column.
Reduction in the size or volume of epiphyses.
An abnormality of the process of blood coagulation. That is, altered ability or inability of the blood to clot.
Distal spinal muscular atrophy (DSMA), also known as distal hereditary motor neuronopathy (dHMN or HMN), is characterized by distal muscle weakness and wasting without significant sensory involvement. For a general phenotypic description and a discussion of genetic heterogeneity of distal SMA, see HMN1 (182960). Harding (1993) classified autosomal recessive distal hereditary motor neuronopathy as dHMN IV (HMN4) and dHMN III (HMN3). Both have juvenile onset and differ only by less severe involvement in HMN3. However, Viollet et al. (2004) reported an extended Lebanese kindred in which both HMN III and HMN IV occurred, suggesting that the same gene was involved in both phenotypes (see Irobi et al., 2006).
Atrophy of the interosseus muscles (including the palmar interossei that lie on the anterior aspect of the metacarpals, the dorsal interosseus muscles of the hand, which lie between the intercarpals, the plantar interosseus muscles, which lie underneath the metatarsal bones, and the dorsal interossei, which are located between the metatarsal bones.
Familial thoracic aortic aneurysm and dissection (familial TAAD) involves problems with the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Familial TAAD affects the upper part of the aorta, near the heart. This part of the aorta is called the thoracic aorta because it is located in the chest (thorax). Other vessels that carry blood from the heart to the rest of the body (arteries) can also be affected.In familial TAAD, the aorta can become weakened and stretched (aortic dilatation), which can lead to a bulge in the blood vessel wall (an aneurysm). Aortic dilatation may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection), allowing blood to flow abnormally between the layers. These aortic abnormalities are potentially life-threatening because they can decrease blood flow to other parts of the body such as the brain or other vital organs, or cause the aorta to break open (rupture).The occurrence and timing of these aortic abnormalities vary, even within the same affected family. They can begin in childhood or not occur until late in life. Aortic dilatation is generally the first feature of familial TAAD to develop, although in some affected individuals dissection occurs with little or no aortic dilatation.Aortic aneurysms usually have no symptoms. However, depending on the size, growth rate, and location of these abnormalities, they can cause pain in the jaw, neck, chest, or back; swelling in the arms, neck, or head; difficult or painful swallowing; hoarseness; shortness of breath; wheezing; a chronic cough; or coughing up blood. Aortic dissections usually cause severe, sudden chest or back pain, and may also result in unusually pale skin (pallor), a very faint pulse, numbness or tingling (paresthesias) in one or more limbs, or paralysis.Familial TAAD may not be associated with other signs and symptoms. However, some individuals in affected families show mild features of related conditions called Marfan syndrome or Loeys-Dietz syndrome. These features include tall stature, stretch marks on the skin, an unusually large range of joint movement (joint hypermobility), and either a sunken or protruding chest. Occasionally, people with familial TAAD develop aneurysms in the brain or in the section of the aorta located in the abdomen (abdominal aorta). Some people with familial TAAD have heart abnormalities that are present from birth (congenital). Affected individuals may also have a soft out-pouching in the lower abdomen (inguinal hernia), an abnormal curvature of the spine (scoliosis), or a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin (dermal capillaries). However, these conditions are also common in the general population. Depending on the genetic cause of familial TAAD in particular families, they may have an increased risk of developing blockages in smaller arteries, which can lead to heart attack and stroke.
Delayed maturation and calcification of any of the tarsal bones, seven bones of the foot comprising the calcaneus, talus, cuboid, navicular, and the cuneiform bones.
LRRK2-related Parkinson disease (PD) is characterized by features consistent with PD of other etiologies: initial motor features of slowly progressive asymmetric tremor at rest and/or bradykinesia, cog-wheel muscle rigidity, postural instability, and gait abnormalities that may include festination and freezing. Non-motor symptoms in LRRK2-related PD occur with similar frequency as observed in typical PD of other etiologies. Onset is generally after age 50 years.
Focal proliferation of glial cells in the substantia nigra.
Parkinsonism is a clinical syndrome that is a feature of a number of different diseases, including Parkinson disease itself, other neurodegenerative diseases such as progressive supranuclear palsy, and as a side-effect of some neuroleptic medications. Some but not all individuals with Parkinsonism show responsiveness to dopaminergic medication defined as a substantial reduction of amelioration of the component signs of Parkinsonism (including mainly tremor, bradykinesia, rigidity, and postural instability) upon administration of dopaminergic medication.
A tendency to hold the chin elevated by about 20 to 30 degrees to compensate for a limitation of eye movement.
Short (hypoplastic) middle phalanx of finger, affecting one or more fingers.
Abnormally early fusion of the bone growth plate.
Senior-Løken syndrome is a rare disorder characterized by the combination of two specific features: a kidney condition called nephronophthisis and an eye condition known as Leber congenital amaurosis.Nephronophthisis causes fluid-filled cysts to develop in the kidneys beginning in childhood. These cysts impair kidney function, initially causing increased urine production (polyuria), excessive thirst (polydipsia), general weakness, and extreme tiredness (fatigue). Nephronophthisis leads to end-stage renal disease (ESRD) later in childhood or in adolescence. ESRD is a life-threatening failure of kidney function that occurs when the kidneys are no longer able to filter fluids and waste products from the body effectively.Leber congenital amaurosis primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. This condition causes vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). Some people with Senior-Løken syndrome develop the signs of Leber congenital amaurosis within the first few years of life, while others do not develop vision problems until later in childhood.
Oculocutaneous albinism type 1 (OCA1) is characterized by hypopigmentation of the skin and hair and the distinctive ocular changes found in all types of albinism, including: nystagmus; reduced iris pigment with iris translucency; reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination; foveal hypoplasia with substantial reduction in visual acuity, usually in the range of 20/100 to 20/400; and misrouting of the optic nerve fiber radiations at the chiasm, resulting in strabismus, reduced stereoscopic vision, and altered visually evoked potentials (VEP). Individuals with OCA1A have white hair, white skin that does not tan, and fully translucent irides, none of which darken with age. At birth, individuals with OCA1B have white or very light yellow hair that darkens minimally with age, white skin that over time develops some minimal generalized pigment and may tan slightly with judicious sun exposure, and blue irides that darken to green/hazel or light brown/tan with age, although transillumination defects persist. Visual acuity may be 20/60 or better in some eyes.
CAMOS syndrome is characterised by the association of a non-progressive congenital ataxia, severe intellectual deficit, optic atrophy and structural anomalies of the skin vessels. It has been described in five children from a large consanguineous Lebanese family. Short stature and microcephaly were also reported. Transmission is autosomal recessive.
An abnormal dilatation of the fourth cerebral ventricle.
Generalized tonic-clonic seizures on awakening are a form of Generalized tonic-clonic seizures that occur upon awaking.
Primary intraosseous vascular malformation, previously called intraosseous hemangioma, is a rare malformation that usually involves the vertebral column and the skull. The most commonly affected bones in the skull are the mandible and the maxilla, and life-threatening bleeding after a simple tooth extraction is frequent (Vargel et al., 2002).
A familial syndrome characterised by gastrointestinal stromal tumours and paragangliomas, often at multiple sites. It is a very rare syndrome presenting at a young age. The gastric stromal sarcomas are multifocal and the paragangliomas are multicentric. The clinical spectrum of this syndrome varies widely, depending on the localisation and the size of the tumours. The vast majority of cases are due to germline mutations of the succinate dehydrogenase (SDH) subunit genes SDHB, SDHC and SDHD. Predisposition to developing these tumours is inherited in an autosomal dominant manner with incomplete penetrance.
Polymicrogyria is a condition characterized by abnormal development of the brain before birth. The surface of the brain normally has many ridges or folds, called gyri. In people with polymicrogyria, the brain develops too many folds, and the folds are unusually small. The name of this condition literally means too many (poly-) small (micro-) folds (-gyria) in the surface of the brain.Polymicrogyria can affect part of the brain or the whole brain. When the condition affects one side of the brain, researchers describe it as unilateral. When it affects both sides of the brain, it is described as bilateral. The signs and symptoms associated with polymicrogyria depend on how much of the brain, and which particular brain regions, are affected.Researchers have identified multiple forms of polymicrogyria. The mildest form is known as unilateral focal polymicrogyria. This form of the condition affects a relatively small area on one side of the brain. It may cause minor neurological problems, such as mild seizures that can be easily controlled with medication. Some people with unilateral focal polymicrogyria do not have any problems associated with the condition.Bilateral forms of polymicrogyria tend to cause more severe neurological problems. Signs and symptoms of these conditions can include recurrent seizures (epilepsy), delayed development, crossed eyes, problems with speech and swallowing, and muscle weakness or paralysis. The most severe form of the disorder, bilateral generalized polymicrogyria, affects the entire brain. This condition causes severe intellectual disability, problems with movement, and seizures that are difficult or impossible to control with medication.Polymicrogyria most often occurs as an isolated feature, although it can occur with other brain abnormalities. It is also a feature of several genetic syndromes characterized by intellectual disability and multiple birth defects. These include 22q11.2 deletion syndrome, Adams-Oliver syndrome, Aicardi syndrome, Galloway-Mowat syndrome, Joubert syndrome, and Zellweger spectrum disorder.
Absence of germinal centers in lymph nodes. Germinal centers are the parts of lymph nodes in which B lymphocytes proliferate, differentiate, mutate through somatic hypermutation and class switch during antibody responses.
A reduced ejection fraction and an enlarged left ventricle chamber, the latter by an increased resistance to filling with increased filling pressures. Systolic dysfunction is clinically associated with left ventricular failure in the presence of marked cardiomegaly.
Sleep bruxism is a stereotyped movement disorder characterized by grinding or clenching of the teeth during sleep (American Academy of Sleep Medicine, 2005). It is a parasomnia, defined as a clinical disorder resulting in undesirable physical phenomena that occur predominantly during sleep. Parasomnias are not abnormalities of the processes responsible for sleep and wake states (summary by Hublin and Kaprio, 2003).
Individuals with familial digital arthropathy-brachydactyly appear normal at birth, with no clinical or radiographic evidence of a developmental skeletal dysplasia. The earliest changes appear during the first decade of life and involve irregularities in the proximal articular surfaces of the distal interphalangeal joints of the hand. By adulthood, all interphalangeal, metacarpophalangeal, and metatarsophalangeal joints are affected by a deforming, painful osteoarthritis. The remainder of the skeleton is clinically and radiographically unaffected, thus distinguishing this disorder from other TRPV4 skeletal dysplasias, the cardinal features of which include abnormalities of the spine and disproportionate short stature (Lamande et al., 2011).
Disproportionately short middle and distal phalanges compared to the hand/foot.
A type of Abnormal glucose tolerance observed following administration of an oral bolus of glucose.
Eating disorders are characterized by severe disturbances in eating behavior that typically have onset during late adolescence and early adulthood. Three major types are recognized: anorexia nervosa (AN), bulimia nervosa (BN; 607499), and eating disorder not otherwise specified (EDNOS). AN is characterized by obsessive fear of weight gain, severely restricted eating, and low body weight. In women, AN has the highest mortality among the psychiatric disorders (Sullivan, 1995). AN is divided into 2 clinical subtypes, restricting anorexia nervosa (RAN) and binge-eating/purging anorexia nervosa (BPAN). BN can occur at any body weight and is characterized by binge-eating and compensatory weight-loss behaviors. Family studies have indicated an increased prevalence of eating disorders in relatives of probands with AN (Lilenfeld et al., 1998), and twin studies (Holland et al., 1984; Wade et al., 2000) have estimated concordance rates for monozygotic twins with AN to be 52 to 56%, whereas concordance rates for dizygotic twins with AN have been estimated to be 5 to 11% (Grice et al., 2002).
Peripheral arterial occlusive disease (PAOD) results from atherosclerosis of large and medium peripheral arteries, as well as the aorta. Many risk factors contribute to PAOD, including smoking, diabetes, hypertension, and hyperlipidemia. PAOD often coexists with coronary artery disease and cerebrovascular disease.
GLUT1 deficiency syndrome is a disorder affecting the nervous system that can have a variety of neurological signs and symptoms. Approximately 90 percent of affected individuals have a form of the disorder often referred to as common GLUT1 deficiency syndrome. These individuals generally have frequent seizures (epilepsy) beginning in the first months of life. In newborns, the first sign of the disorder may be involuntary eye movements that are rapid and irregular. Babies with common GLUT1 deficiency syndrome have a normal head size at birth, but growth of the brain and skull is often slow, which can result in an abnormally small head size (microcephaly). People with this form of GLUT1 deficiency syndrome may have developmental delay or intellectual disability. Most affected individuals also have other neurological problems, such as stiffness caused by abnormal tensing of the muscles (spasticity), difficulty in coordinating movements (ataxia), and speech difficulties (dysarthria). Some experience episodes of confusion, lack of energy (lethargy), headaches, or muscle twitches (myoclonus), particularly during periods without food (fasting).About 10 percent of individuals with GLUT1 deficiency syndrome have a form of the disorder often known as non-epileptic GLUT1 deficiency syndrome, which is usually less severe than the common form. People with the non-epileptic form do not have seizures, but they may still have developmental delay and intellectual disability. Most have movement problems such as ataxia or involuntary tensing of various muscles (dystonia); the movement problems may be more pronounced than in the common form.Several conditions that were originally given other names have since been recognized to be variants of GLUT1 deficiency syndrome. These include paroxysmal choreoathetosis with spasticity (dystonia 9); paroxysmal exercise-induced dyskinesia and epilepsy (dystonia 18); and certain types of epilepsy. In rare cases, people with variants of GLUT1 deficiency syndrome produce abnormal red blood cells and have uncommon forms of a blood condition known as anemia, which is characterized by a shortage of red blood cells.
Repeated episodes of sudden-onset and transient lethargy.
Microcephaly (HP:0000252) with onset in the postnatal period, that is, the head circumference is in the normal range at birth but falls behind normal values later in development.
Sudden-onset episode of abnormal, involuntary eye movements.
A form of astigmatism in which one meridian is hyperopic while the one at a right angle to it has no refractive error.
In spermatogenic failure-3, primary infertility is associated with nonobstructive asthenozoospermia (Dirami et al., 2013). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Congenital hyperinsulinism is a condition that causes individuals to have abnormally high levels of insulin, which is a hormone that helps control blood sugar levels. People with this condition have frequent episodes of low blood sugar (hypoglycemia). In infants and young children, these episodes are characterized by a lack of energy (lethargy), irritability, or difficulty feeding. Repeated episodes of low blood sugar increase the risk for serious complications such as breathing difficulties, seizures, intellectual disability, vision loss, brain damage, and coma.The severity of congenital hyperinsulinism varies widely among affected individuals, even among members of the same family. About 60 percent of infants with this condition experience a hypoglycemic episode within the first month of life. Other affected children develop hypoglycemia by early childhood. Unlike typical episodes of hypoglycemia, which occur most often after periods without food (fasting) or after exercising, episodes of hypoglycemia in people with congenital hyperinsulinism can also occur after eating.
Seckel syndrome is a rare autosomal recessive disorder characterized by growth retardation, microcephaly with mental retardation, and a characteristic facial appearance (Borglum et al., 2001). For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600).
An abnormal reduction in sensation in the distal portions of the extremities.
Recessive multiple epiphyseal dysplasia (EDM4/rMED) is characterized by joint pain (usually in the hips or knees); malformations of hands, feet, and knees; and scoliosis. Approximately 50% of affected individuals have an abnormal finding at birth, e.g., clubfoot, clinodactyly, or (rarely) cystic ear swelling. Onset of articular pain is variable but usually occurs in late childhood. Stature is usually within the normal range prior to puberty; in adulthood, stature is only slightly diminished and ranges from 150 to 180 cm. Functional disability is mild.
Van der Woude syndrome (VWS) is a dominantly inherited developmental disorder characterized by pits and/or sinuses of the lower lip, and cleft lip and/or cleft palate (CL/P, CP). It is the most common cleft syndrome. For a discussion of genetic heterogeneity of van der Woude syndrome, see VWS1 (119300).
A delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts.
Specific language impairment (SLI) is a common developmental disorder characterized by difficulty in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors (summary by Newbury et al., 2009). Genetic Heterogeneity of Specific Language Impairment Multiple loci for specific language impairment have been mapped, including SLI1 on chromosome 16q; SLI2 (606712) on chromosome 19q; SLI3 (607134) on chromosome 13q21; SLI4 (612514) on chromosome 7q35-36; and SLI5 (615432), caused by mutation in the TM4SF20 gene (615404) on chromosome 2q36.
Split-hand/split-foot malformation (SHFM) is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM5 have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting (Elliott and Evans, 2006). For additional phenotypic information and a discussion of genetic heterogeneity in this disorder, see SHFM1 (183600).
ADCY5-related dyskinesia is characterized by infantile to late-adolescent onset of paroxysmal choreiform, myoclonic, and/or dystonic movements that involve the limbs, neck, and/or face. Dyskinesias are often exacerbated by anxiety (although not by startle, caffeine, or alcohol). Facial ""twitches"" (previously thought to be myokymia) involving the periorbital and/or perioral muscles may also be present. Hypotonia and delayed motor milestones may be present in more severely affected infants. The movement disorder can be static or slowly progressive, with a tendency to stabilize in early middle age. Intellect and life span are normal.
Dilated cardiomyopathy, a disorder characterized by cardiac dilation and reduced systolic function, represents an outcome of a heterogeneous group of inherited and acquired disorders. For background and phenotypic information on dilated cardiomyopathy, see CMD1A (115200).
Hypermethioninemia is an excess of a particular protein building block (amino acid), called methionine, in the blood. This condition can occur when methionine is not broken down (metabolized) properly in the body.People with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit intellectual disability and other neurological problems; delays in motor skills such as standing or walking; sluggishness; muscle weakness; liver problems; unusual facial features; and their breath, sweat, or urine may have a smell resembling boiled cabbage.Hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia and galactosemia, which also involve the faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula.
Waardenburg syndrome type II (WS2) is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (Selicorni et al., 2002). WS type 2C (WS2C) maps to chromosome 8p. Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; 193510). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS3 (148820), and WS4 (277580).
Spinocerebellar ataxia type 15 (SCA15) is characterized by slowly progressive gait and limb ataxia, often in combination with ataxic dysarthria, titubation, upper limb postural tremor, mild hyperreflexia, gaze-evoked nystagmus, and impaired vestibuloocular reflex gain. Onset is between ages seven and 72 years, usually with gait ataxia but sometimes with tremor. Affected individuals remain ambulatory for ten to 54 years after symptom onset. Mild dysphagia usually after two or more decades of symptoms has been observed in members of multiple affected families and movement-induced oscillopsia has been described in one member of an affected family.
Primary familial brain calcification (PFBC) is a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas visualized on neuroimaging. Most affected individuals are in good health during childhood and young adulthood and typically present in the fourth to fifth decade with a gradually progressive movement disorder and neuropsychiatric symptoms. The movement disorder first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia. Seizures of various types occur frequently, some individuals experience chronic headache and vertigo; urinary urgency or incontinence may be present.
High density lipoproteins (HDLs) are antiatherogenic lipoproteins that have a major role in transporting cholesterol from peripheral tissues to the liver, where it is removed. Epidemiologic studies show that low levels of high density lipoprotein cholesterol (HDLC; see 604091) are associated with an increased risk of coronary heart disease and an increased mortality rate. HDLC levels are influenced by several genetic and nongenetic factors. Nongenetic factors include smoking, which decreases the HDLC level. Exercise and alcohol increase HDLC levels. Decreased HDLC is often associated with other coronary heart disease risk factors such as obesity, hyperinsulinemia and insulin resistance, hypertriglyceridemia, and hypertension.
MDDGB5 is an autosomal recessive congenital muscular dystrophy with mental retardation and structural brain abnormalities (Brockington et al., 2001). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Mercuri et al., 2006). For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
Amyotrophy affecting the muscles of the shoulder girdle.
Waardenburg syndrome type I (WS1) is an auditory-pigmentary disorder comprising congenital sensorineural hearing loss and pigmentary disturbances of the iris, hair, and skin, along with dystopia canthorum (lateral displacement of the inner canthi). The hearing loss in WS1, observed in approximately 60% of affected individuals, is congenital, typically non-progressive, either unilateral or bilateral, and sensorineural. Most commonly, hearing loss in WS1 is bilateral and profound (>100 dB). The majority of individuals with WS1 have either a white forelock or early graying of the scalp hair before age 30 years. The classic white forelock observed in approximately 45% of individuals is the most common hair pigmentation anomaly seen in WS1. Affected individuals may have complete heterochromia iridium, partial/segmental heterochromia, or hypoplastic or brilliant blue irides. Congenital leukoderma is frequently seen on the face, trunk, or limbs.
A hereditary disorder associated with impaired DNA double-strand break repair mechanisms with characteristics of microcephaly, unusual facial features, growth and developmental delay, skin anomalies, and pancytopenia, which is associated with combined immunodeficiency. Caused by mutations in the LIG4 gene (13q22-q34). The resulting defect of DNA ligase IV, a component of the classical non-homologous end-joining (NHEJ) pathway, affects the major mechanism of DNA double-strand break repair. Transmission is autosomal recessive.
Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other autoimmune diseases. It is a genetically complex disorder involving multiple susceptibility genes and unknown environmental triggers. Patients with generalized vitiligo have elevated frequencies of other autoimmune diseases, suggesting that these diseases involve shared genetic components (summary by Jin et al., 2010). Genetic Heterogeneity of Vitiligo-Associated Multiple Autoimmune Disease Susceptibility Additional forms of vitiligo-associated multiple autoimmune disease susceptibility have been mapped to chromosomes 1p31 (VAMAS2, 607836, associated with mutation in the FOXD3 gene, 611539), 7 (VAMAS3; 608391), 8 (VAMAS4; 608392), 4 (VAMAS5; 609400), and 6p21.3 (VAMAS6; 193200).
Oculocutaneous albinism type 4 (OCA4) is characterized by hypopigmentation of the hair and skin plus the characteristic ocular changes found in all other types of albinism, including: nystagmus; reduced iris pigment with iris translucency; reduced retinal pigment with visualization of the choroidal blood vessels on ophthalmoscopic examination; foveal hypoplasia associated with reduction in visual acuity; and misrouting of the optic nerves at the chiasm associated with alternating strabismus, reduced stereoscopic vision, and an altered visual evoked potential (VEP). Individuals with OCA4 are usually recognized within the first year of life because of hypopigmentation of the hair and skin and the ocular features of nystagmus and strabismus. Vision is likely to be stable after early childhood. The amount of cutaneous pigmentation in OCA4 ranges from minimal to near normal. Newborns with OCA4 usually have some pigment in their hair, with color ranging from silvery white to light yellow. Hair color may darken with time, but does not vary significantly from childhood to adulthood.
An increased concentration of all types of amino acid in the urine.
PHACE is an acronym for a neurocutaneous syndrome encompassing the following features: posterior fossa brain malformations, hemangiomas of the face (large or complex), arterial anomalies, cardiac anomalies, and eye abnormalities. The association is referred to as PHACES when ventral developmental defects, such as sternal clefting or supraumbilical raphe, are present (summary by Bracken et al., 2011).
A mode of inheritance that is observed for dominant traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked dominant disorders tend to manifest very severely in affected males. The severity of manifestation in females may depend on the degree of skewed X inactivation.
Hemangioma is a benign tumor of the vascular endothelial cells. This term refers to facial hemangiomas that have a plaque-like morphology.
Charcot-Marie-Tooth disease is a clinically and genetically heterogeneous disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. CMT neuropathy is subdivided into CMT1 (see 118200) and CMT2 (see 118210) types on the basis of electrophysiologic and neuropathologic criteria. CMT1 is a demyelinating neuropathy, whereas CMT2 is an axonal neuropathy. Most patients with CMT are classified as having CMT1 or CMT2 by use of a cut-off value of 38 m/s for the motor median nerve conduction velocity (NCV). However, in some families with CMT, patients have motor median NCVs ranging from 25 to 45 m/s. Davis et al. (1978) proposed that this form be designated 'intermediate' CMT. For a phenotypic description and a discussion of genetic heterogeneity of dominant intermediate CMT neuropathy, see CMTDIB (606482).
DNM2-related intermediate Charcot-Marie-Tooth neuropathy (DI-CMTB) has a classic, mild to moderately severe Charcot-Marie-Tooth hereditary neuropathy phenotype that often includes pes cavus foot deformity, depressed tendon reflexes, distal muscle weakness and atrophy, and sensory loss. Age of onset varies greatly among affected individuals and ranges from age two to 50 years. It is unusual for individuals with DI-CMTB to become wheelchair bound. Other findings include asymptomatic neutropenia and early-onset cataracts (often noted in childhood before age 15 years).
Repeated episodes of segmental demyelination and remyelination lead to the accumulation of supernumerary Schwann cells around axons, which is referred to as onion bulb formation. This finding affects peripheral nerves.
Persistent polyclonal B-cell lymphocytosis (PPBL) is characterized by chronic, stable, persistent, and polyclonal lymphocytosis, the presence of binucleated lymphocytes in the peripheral blood, and a polyclonal increase in serum IgM. It is significantly associated with cigarette smoking (summary by Cornet et al., 2009).
Huntington disease-like 2 (HDL2) typically presents in midlife with a relentless progressive triad of movement, emotional, and cognitive abnormalities progressing to death over ten to 20 years. In some individuals the presentation resembles juvenile-onset Huntington disease (HD) or the Westphal variant of HD, usually presenting in the fourth decade (ages 29 to 41 years) with diminished coordination and weight loss despite increase in food intake. Neurologic abnormalities include parkinsonism (rigidity, bradykinesia, tremor), dysarthria, and hyperreflexia. In others the presentation is more variable but, in general, corresponds to typical HD.
Classic-like Ehlers-Danlos syndrome is a connective tissue disorder characterized by hyperextensible skin, hypermobile joints, and tissue fragility (Burch et al., 1996). For a phenotypic description of classic-type EDS, see 130000.
Reduced side to side width of the pelvis.
Epileptic encephalopathy-9 is an X-linked disorder characterized by seizure onset in infancy and mild to severe intellectual impairment. Autistic and psychiatric features have been reported in some individuals. The disorder affects heterozygous females only; transmitting males are unaffected (summary by Jamal et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
In mammals, the potential imbalance of gene expression for the two X chromosomes in females is resolved by inactivating one X in all somatic tissues. In the embryo proper, the process of X inactivation is considered to be random between the maternal and paternal chromosomes. Thus, most females have mosaic expression of maternal and paternal alleles of X chromosome loci, with a contribution of about 50% from each chromosome. However, some females show a skewed ratio of X inactivation, which can be due to negative or positive selection, or to an underlying primary genetic process. Belmont (1996) observed familial clustering of females with highly skewed patterns of X inactivation and reviewed the genetic control of X inactivation. Genetic Heterogeneity of Skewed X Inactivation See also SXI2 (300179) for a locus that maps to chromosome Xq25-q26.
A syndrome with characteristics of immune deficiency and neurological disorders in females and neonatal death in males. The syndrome has been described in only one family with nine affected individuals (five males and four females) spanning two generations. Symptomatic females present slowly progressive proximal muscle weakness, leg hyperreflexia, pes cavus, increased muscle tone in the legs, poor bladder function, static reduced night vision and frequent sinopulmonary infections associated with IgG2 deficiency. Males present with low birth weight and severe hypotonia that leads to death in the neonatal period. The gene locus has been mapped to Xq26-qter.
X-linked congenital stationary night blindness (CSNB) is characterized by: non-progressive retinal findings of reduced visual acuity ranging from 20/30 to 20/200; defective dark adaptation; refractive error, most typically myopia ranging from low (-0.25 diopters [D] to -4.75 D) to high (=-10.00 D) but occasionally hyperopia; nystagmus; strabismus; normal color vision; and normal fundus examination. Two overlapping, yet distinct, phenotypes are recognized: Complete CSNB (CSNB1A), caused by pathogenic variants in NYX (45%). Incomplete CSNB (CSNB2A), caused by pathogenic variants in CACNA1F (55%).
The presence of female external genitalia in a person with a male karyotype.
Normally, the female reproductive canal is connected to the internal genitalia. ""Blind vagina"" denotes cases, where this canal ends in a sac.
A gonadal sex cord-stromal tumor with malignant characteristics. It includes the poorly differentiated ovarian Sertoli-Leydig cell tumor, malignant ovarian granulosa cell tumor, malignant ovarian steroid cell tumor, and malignant ovarian thecoma.
Subcortical band heterotopia is a condition in which nerve cells (neurons) do not move (migrate) to their proper locations in the fetal brain during early development. (Heterotopia means ""out of place."") Normally, the neurons that make up the outer surface of the brain (cerebral cortex) are distributed in a well-organized and multi-layered way. In people with subcortical band heterotopia, some neurons that should be part of the cerebral cortex do not reach it. These neurons stop their migration process in areas of the brain where they are not supposed to be and form band-like clusters of tissue. Since these bands are located beneath the cerebral cortex, they are said to be subcortical. In most cases, the bands are symmetric, which means they occur in the same places on the right and left sides of the brain.The abnormal brain development causes neurological problems in people with subcortical band heterotopia. The signs and symptoms of the condition depend on the size of the bands and the lack of development of the cerebral cortex. The signs and symptoms can vary from severe intellectual disability and seizures that begin early in life and affect both sides of the brain (generalized seizures) to normal intelligence with seizures occurring later in life and affecting only one side of the brain (focal seizures). Some affected individuals also have weak muscle tone (hypotonia), loss of fine motor skills such as using utensils, or behavioral problems. Subcortical band heterotopia is typically found when brain imaging is done following the onset of seizures, usually in adolescence or early adulthood.
X-linked deafness-4 is a nonsyndromic form of progressive hearing loss with postlingual onset. Affected males show earlier onset of hearing loss than affected females (summary by del Castillo et al., 1996).
PPM-X syndrome is a condition characterized by psychotic disorders (most commonly bipolar disorder), a pattern of movement abnormalities known as parkinsonism, and mild to severe intellectual disability with impaired language development. Other symptoms may include muscle stiffness (spasticity), exaggerated reflexes, and an abnormally small head (microcephaly). Affected males may have enlarged testes (macro-orchidism). Not all affected individuals have all these symptoms, but most have intellectual disability. Males with this condition are typically more severely affected than females, who usually have only mild intellectual disability or learning disabilities.
FLNA-related periventricular nodular heterotopia (PVNH), a neuronal migration disorder, is characterized by the presence of uncalcified nodules of neurons ectopically situated along the surface of the lateral ventricles. Affected individuals are predominantly heterozygous females; males most often show early lethality. Affected females present with seizures at an average age of 14-15 years; intelligence ranges from normal to borderline. The risk for cardiovascular disease, stroke, and other vascular/coagulation problems appears to be increased.
Swyer syndrome is a condition that affects sexual development. Sexual development is usually determined by an individual's chromosomes; however, in Swyer syndrome, sexual development does not match the affected individual's chromosomal makeup.People usually have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Girls and women typically have two X chromosomes (46,XX karyotype), while boys and men usually have one X chromosome and one Y chromosome (46,XY karyotype). In Swyer syndrome, individuals with one X chromosome and one Y chromosome in each cell, the pattern typically found in boys and men, have female reproductive structures.People with Swyer syndrome have typical female external genitalia. The uterus and fallopian tubes are normally-formed, but the gonads (ovaries or testes) are not functional; affected individuals have undeveloped clumps of tissue called streak gonads. Because of the lack of development of the gonads, Swyer syndrome is also called 46,XY complete gonadal dysgenesis. The residual gonadal tissue often becomes cancerous, so it is usually removed surgically early in life.People with Swyer syndrome are typically raised as girls and have a female gender identity. Because they do not have functional ovaries, affected individuals usually begin hormone replacement therapy during adolescence to induce menstruation and development of female secondary sex characteristics such as breast enlargement and uterine growth. Hormone replacement therapy also helps reduce the risk of reduced bone density (osteopenia and osteoporosis). Women with this disorder do not produce eggs (ova), but they may be able to become pregnant with a donated egg or embryo.Swyer syndrome usually affects only sexual development; such cases are called isolated Swyer syndrome. However, depending on the genetic cause, Swyer syndrome may also occur along with health conditions such as nerve problems (neuropathy) or as part of a syndrome such as campomelic dysplasia, which causes severe skeletal abnormalities.
Zunich neuroectodermal syndrome is an extremely rare autosomal recessive multisystem disorder clinically characterized by colobomas, congenital heart defects, migratory ichthyosiform dermatosis, mental retardation, and ear anomalies (CHIME). Other clinical features include distinctive facial features, abnormal growth, genitourinary abnormalities, seizures, and feeding difficulties (summary by Ng et al., 2012). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
A fetus or infant who is larger than expected for the age or gender, or who has a birth weight greater than the 90th percentile.
The presence of xanthine-containing calculi (stones) in the kidneys.
A rare intellectual disability syndrome with manifestations of severe intellectual disability, characteristic facial features (low anterior hairline, upward slanting palpebral fissures, ocular hypertelorism, broad, bulbous nose, large ears with helix incompletely developed, thick lips, and micrognathia) and additional anomalies including peripheral joint contractures, delayed skeletal maturation, bilateral cleft lip and palate, strabismus, terminal hypoplasia of fingers, hypospadias, and bilateral inguinal hernias.
A partial dislocation of the atlantoaxial joints.
An increased concentration of non ceruloplasmin bound copper in the blood.
A multiple congenital anomalies syndrome with characteristics of poliosis, distinct facial features (epicanthal folds, hypertelorism, posterior rotation of ears, prominent philtrum, high-arched palate) and congenital anomalies/malformations of the eye (blue sclera), cardiopulmonary (atrial septal defect, prominent thoracic and abdominal veins) and skeletal (clinodactyly, syndactyly of the fingers and second and third toes) systems. There have been no further descriptions in the literature since 1980.
Whistling face syndrome is characterized by an atypical facial appearance with anomalies of the hands and feet. Most cases show autosomal dominant inheritance: see distal arthrogryposis 2A (DA2A; 193700). There are rare reports of presumably autosomal recessive inheritance (summary by Altunhan et al., 2010).
An abnormality of facial morphology characterized by a small mouth opening and constant contraction of the lips as if the patient were whistling.
Limitation in the ability to open the mouth.
Arteriosclerosis occuring at an age that is younger than usual.
Weissenbacher-Zweymüller syndrome is a condition that affects bone growth. It is characterized by skeletal abnormalities, hearing loss, and distinctive facial features. The features of this condition significantly overlap those of two similar conditions, otospondylomegaepiphyseal dysplasia (OSMED) and Stickler syndrome type III. All of these conditions are caused by mutations in the same gene, and in some cases, it can be difficult to tell them apart. Some researchers believe they represent a single disorder with a range of signs and symptoms.Infants born with Weissenbacher-Zweymüller syndrome are smaller than average because the bones in their arms and legs are unusually short. The thigh and upper arm bones are wider than usual at the ends (described as dumbbell-shaped), and the bones of the spine (vertebrae) may also be abnormally shaped. High-frequency hearing loss occurs in some cases. Distinctive facial features include wide-set protruding eyes, a small and upturned nose with a flat bridge, and a small lower jaw. Some affected infants are born with an opening in the roof of the mouth (a cleft palate).Most people with Weissenbacher-Zweymüller syndrome experience significant ""catch-up"" growth in the bones of the arms and legs during childhood. As a result, adults with this condition are not unusually short. However, affected adults still have other signs and symptoms of Weissenbacher-Zweymüller syndrome, including distinctive facial features and hearing loss.
Waardenburg syndrome type 4 (WS4), also known as Waardenburg-Shah syndrome, is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes, congenital sensorineural hearing loss, and Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 4A is caused by mutation in the EDNRB gene (131244). Clinical Variability of Waardenburg Syndrome Types 1-4 Waardenburg syndrome has been classified into 4 main phenotypes. Type I Waardenburg syndrome (WS1; 193500) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type II (WS2) is distinguished from type I by the absence of dystopia canthorum. WS type III (WS3; 148820) has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type 4 has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010). Genetic Heterogeneity of Waardenburg Syndrome Type 4 Waardenburg syndrome type 4 is genetically heterogeneous. WS4B (613265) is caused by mutation in the EDN3 gene (131242) on chromosome 20q13, and WS4C (613266) is caused by mutation in the SOX10 gene (602229) on chromosome 22q13.
TSEN54-related pontocerebellar hypoplasia (PCH) includes three PCH types (PCH2, 4, and 5) that share characteristic neuroradiologic and neurologic findings. The three types (which differ mainly in life expectancy) were thought to be distinct entities before their molecular basis was known. Children with PCH2 usually succumb before age ten years, whereas those with PCH4 and 5 usually succumb as neonates. Children with PCH2 have generalized clonus, incoordination of sucking and swallowing, impaired motor and cognitive development with lack of voluntary motor development, central visual impairment, and an increased risk for rhabdomyolysis complicating severe infections. Epilepsy is present in approximately 50%. Neonates with PCH4 often have seizures, multiple joint contractures (""arthrogryposis""), generalized clonus, and central respiratory impairment. PCH5, which resembles PCH4, has been described in one family.
An impairment of the ability to track objects with the ocular smooth pursuit system, a class of rather slow eye movements that minimizes retinal target motion.
Ataxia with vitamin E deficiency (AVED) generally manifests in late childhood or early teens between ages five and 15 years. The first symptoms include progressive ataxia, clumsiness of the hands, loss of proprioception, and areflexia. Other features often observed are dysdiadochokinesia, dysarthria, positive Romberg sign, head titubation, decreased visual acuity, and positive Babinski sign. The phenotype and disease severity vary widely among families with different pathogenic variants; age of onset and disease course are more uniform within a given family, but symptoms and disease severity can vary even among sibs.
Deficiency of all vitamin K-dependent clotting factors leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. Acquired forms of the disorder can be caused by intestinal malabsorption of vitamin K. Familial multiple coagulation factor deficiency is rare. Clinical symptoms of the disease include episodes of intracranial hemorrhage in the first weeks of life, sometimes leading to a fatal outcome. The pathomechanism is based on a reduced hepatic gamma-carboxylation of glutamic acid residues of all vitamin K-dependent blood coagulation factors, as well as the anticoagulant factors protein C (612283) and protein S (176880). Posttranslational gamma-carboxylation of proteins enables the calcium-dependent attachment of the proteins to the phospholipid bilayer of membranes, an essential prerequisite for blood coagulation. Vitamin K1 acts as a cofactor for the vitamin K-dependent carboxylase in liver microsomes, GGCX. Genetic Heterogeneity of Combined Deficiency of Vitamin K-Dependent Clotting Factors Combined deficiency of vitamin K-dependent clotting factors-2 (VKFCD2; 607473) is caused by mutation in the gene encoding vitamin K epoxide reductase (VKORC1; 608547) on chromosome 16p11.
Abnormal outward curving (protuberance) of the junction of ribs and costal cartilage.
Loss of bone mass occurring beneath the periosteum (the periosteum is the connective-tissue membrane that surrounds all bones except at the articular surfaces). This process may create a serrated and lace-like appearance in periosteal cortical bone.
A decreased concentration of methionine in the blood.
Decreased concentration of adenosylcobalamin. Adenosylcobalamin is one of the active forms of vitamin B12.
An abnormality of Krebs cycle metabolism that is characterized by a decreased rate of methylmalonyl-CoA mutase activity.
A reduction in methionine synthase activity.
Intestinal pseudo-obstruction is a condition characterized by impairment of the muscle contractions that move food through the digestive tract. It can occur at any time of life, and its symptoms range from mild to severe. The condition may arise from abnormalities of the gastrointestinal muscles themselves (myogenic) or from problems with the nerves that control the muscle contractions (neurogenic).Intestinal pseudo-obstruction leads to a buildup of partially digested food in the intestines. This buildup can cause abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those of an intestinal blockage (obstruction), but in intestinal pseudo-obstruction no blockage is found.Depending on the cause of intestinal pseudo-obstruction, affected individuals can have additional signs and symptoms. Some people with intestinal pseudo-obstruction have bladder dysfunction such as an inability to pass urine. Other features may include decreased muscle tone (hypotonia) or stiffness (spasticity) of the torso and limbs, weakness in the muscles that control eye movement (ophthalmoplegia), intellectual disability, seizures, unusual facial features, or recurrent infections.When intestinal pseudo-obstruction occurs by itself, it is called primary or idiopathic intestinal pseudo-obstruction. The disorder can also develop as a complication of another health problem; in these cases, it is called secondary intestinal pseudo-obstruction. The condition can be episodic (acute) or persistent (chronic).
A rare congenital heart malformation with characteristics of underdevelopment of the right ventricle associated with patent foramen ovale or interauricular communication and normally developed tricuspid and pulmonary valves. Manifests with severe cyanosis, congestive heart failure, and in severe cases, death in early infancy.
The presence of a supernumerary finger or toe (not a thumb or hallux) involving the third or fourth metacarpal/tarsal with associated osseous syndactyly.
A central Y-shaped metacarpal is the result of a partial fusion of two central metacarpals (i.e., metacarpals 2-4) of the hand, with the two arms of the Y pointing in the distal direction. Central Y-shaped metacarpals may be seen as a result of a central polydactyly with partial fusion of the duplicated metacarpal.
VACTERL describes a constellation of congenital anomalies, including vertebral anomalies, anal atresia, congenital cardiac disease, tracheoesophageal fistula, renal anomalies, radial dysplasia, and other limb defects; see 192350. Cases of familial VACTERL with hydrocephalus (H) have been reported with suggestion of autosomal recessive or X-linked inheritance (see 314390). Other patients thought to have VACTERL-H, including 2 unrelated infants reported by Porteous et al. (1992), had been found to have Fanconi anemia (see 227650). Porteous et al. (1992) suggested that chromosomal breakage studies should be performed in all cases of VACTERL/VACTERL-H to rule out Fanconi anemia. Alter et al. (2007) noted that a VATER phenotype had been reported in Fanconi anemia of complementation groups A (227650), C (227645), D1 (605724), E (600901), F (603467), and G (614082). X-linked VACTERL-H is also associated with mutations in the FANCB gene (300515).
Reduced functioning of the vestibular apparatus.
The Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome (AARRS) is a rare autosomal recessive disorder characterized by severe malformations of upper and lower limbs with severely hypoplastic pelvis and abnormal genitalia. The disorder is believed to represent a defect of dorsoventral patterning and outgrowth of limbs (summary by Kantaputra et al., 2010).
A herniation of meninges through a congenital bone defect in the skull in the occipital region.
Median longitudinal ear length greater than two SD above the mean determined by the maximal distance from the superior aspect to the inferior aspect of the external ear.
Small or missing phalangeal bones of the fingers of the hand.
Absence or underdevelopment of the tarsal bones.
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
Increased concentration of pyruvic acid in the urine.
Increased concentration of 4-hydroxyphenylacetic acid in the urine.
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
An increased concentration of 5-aminolevulinic acid (CHEBI:17549) in the urine.
Muscular atrophy affecting muscles in the distal portions of the extremities.
Absence or underdevelopment of the eyebrow.
Overconstriction, or narrowness of the diaphysis and metaphysis of long bones.
Graves disease is an autoimmune disorder in which antibodies to the thyrotropin receptor (TSHR; 603372) result in constitutive activation of the receptor and increased levels of thyroid hormone. Wilkin (1990) reviewed endocrine disorders of hormone excess and hormone deficiency resulting from receptor autoimmunity.
Approximately 10% of patients with congenital hypothyroidism harbor inborn errors of metabolism in one of the steps for thyroid hormone synthesis in thyrocytes (Vono-Toniolo et al., 2005). Dyshormonogenesis can be caused by recessive defects at any of the steps required for normal thyroid hormone synthesis. In untreated patients thyroid dyshormonogenesis is typically associated with goitrous enlargement of the thyroid secondary to long-term thyrotropin (TSH; see 188540) stimulation. Park and Chatterjee (2005) reviewed the genetics of primary congenital hypothyroidism, summarizing the different phenotypes associated with known genetic defects and proposing an algorithm for investigating the genetic basis of the disorder. Genetic Heterogeneity of Thyroid Dyshormonogenesis Other forms of thyroid hormone dysgenesis include TDH2A (274500), caused by mutation in the thyroid peroxidase gene (TPO; 606765) on 2p25; Pendred syndrome, a form of thyroid hormone dysgenesis associated with deafness (TDH2B; 274600) and caused by mutation in the SLC26A4 gene (605646) on 7q31; TDH3 (274700), caused by mutation in the thyroglobulin gene (TG; 188450) on 8q24; TDH4 (274800), caused by mutation in the iodotyrosine deiodinase gene (IYD; 612025) on 6q25; TDH5 (274900), caused by mutation in the DUOXA2 gene (612772) on 15q21; and TDH6 (607200), caused by mutation in the DUOX2 gene (606759) on 15q21.
This syndrome has characteristics of intrauterine growth retardation, renal dysgenesis and a unilobed or absent thymus. It has been described in three girls born to a nonconsanguineous couple.
Thymomas are low-grade epithelial cancers of the thymus. Familial occurrence of thymoma is rare.
Missing radius bone on both sides associated with congenital failure of development.
Naevus flammeus localised in the skin of the forehead.
An increased concentration of threonine in the blood.
Three M syndrome is characterized by severe pre- and postnatal growth deficiency (final height 5-6 SD below the mean; i.e., 120-130 cm), characteristic facies, and normal intelligence. Additional features of three M syndrome include short broad neck, prominent trapezii, deformed sternum, short thorax, square shoulders, winged scapulae, hyperlordosis, short fifth fingers, prominent heels, and loose joints. Males with three M syndrome have hypogonadism and occasionally hypospadias.
Lack of external genitalia in a male or female individual.
Any abnormality of the diaphragm, the sheet of skeletal muscle that separates the thoracic cavity from the abdominal cavity.
Underdevelopment of the alveolar process (also known as alveolar bone). [HPO:probinson]
Hypoplasia of the maxillozygomatic complex.
Teebi-Shaltout syndrome is characterized by slow hair growth, scaphocephaly with prominent forehead, bitemporal depression, absence of primary teeth, camptodactyly, and caudal appendage with sacral dimple (summary by Aldemir et al., 2013).
Onset of signs or symptoms of disease between 28 days to one year of life.
Susceptibility to lysis by alloreactive natural killer (NK) cells is an autosomal recessive trait (thus differing from the behavior of conventional MHC products) (Ciccone et al., 1990; Ciccone et al., 1990).
A type of dystonia that affects all or most of the body.
Increased concentration of SO3(2-), i.e., sulfite, in the urine.
Decreased concentration of sulfate in the urine.
Subvalvular stenosis is caused by a diaphragm-like membrane. The stenosis is clinically manifested like any other form of aortic stenosis but is often associated with some aortic insufficiency.
A cessation of the development of a child in the areas of motor skills, speech and language, cognitive skills, and social and/or emotional skills.
An abnormally wide femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Diminished length of a metatarsal bone, with resultant proximal displacement of the associated toe.
A face with a rounded and slightly elongated outline.
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
A skin texture that is unusually soft (and may feel silky), and has a malleable consistency resembling that of dough.
An autosomal recessive form of brachyolmia a group of rare genetic skeletal disorders, with features of short stature, short trunk, platyspondyly and corneal opacities.
Early ossification of the costochondral junction, which is the joint between the ribs and costal cartilage in the front of the rib cage.
Rock et al. (2008) provided an overview of the brachyolmias, a heterogeneous group of skeletal dysplasias that affect primarily the spine. Type 1 brachyolmia includes the Hobaek and Toledo (BCYM1B; 271630) forms, which are inherited in an autosomal recessive fashion. Both forms of type 1 are characterized by scoliosis, platyspondyly with rectangular and elongated vertebral bodies, overfaced pedicles, and irregular, narrow intervertebral spaces. The Toledo form is distinguished by the presence of corneal opacities and precocious calcification of the costal cartilage. Type 2 brachyolmia (BCYM2; 613678), sometimes referred to as the Maroteaux type, is also an autosomal recessive disorder, primarily distinguished from type 1 by rounded vertebral bodies and less overfaced pedicles. Some cases are associated with precocious calcification of the falx cerebri. Type 3 brachyolmia (BCYM3; 113500) is an autosomal dominant form, caused by mutation in the TRPV4 gene (605427), with severe kyphoscoliosis and flattened, irregular cervical vertebrae. Paradoxically, although the limbs are mildly shortened in all types of brachyolmia, they show minimal epiphyseal and metaphyseal abnormalities on radiographs. Type 4 brachyolmia (BCYM4; 612847) is an autosomal recessive form, caused by mutation in the PAPSS2 gene (603005), with mild epiphyseal and metaphyseal changes.
An abnormally flat form of the proximal epiphysis of the radius.
Syndrome with the association of spondylocostal dysostosis with anal and genitourinary malformations (anal atresia and agenesis of external and internal genitalia). To date, only four cases have been described in the literature.
A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.
Narrowing (becoming gradually narrower) of the distance between lumbar vertebral pedicles that gets progressively more severe towards to caudal (lower) end of the vertebral column.
Longitudinal densities on radiographs located in a metaphysis (the narrow region of a long bone between the epiphysis and the diaphysis).
Extremely rare syndrome with features of spastic ataxia in association with bilateral congenital cataract, corneal dystrophy, and nonaxial myopia. It has been described in an inbred Bedouin family. Immunological abnormalities were frequent. Transmission is autosomal recessive and the disease is monogenic.
Syndrome with the unusual combination of spinocerebellar degeneration and corneal dystrophy. Three sisters born to normal consanguineous parents have been reported, one of who had only minor spinocerebellar signs without ocular involvement. This autosomal recessive syndrome differs from the Mousa-Al-Din-Al-Nassar syndrome by the subnormal intellectual development and the epithelial (versus stromal) nature of the corneal dystrophy.
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Deterioration or loss of the tissues of the cochlea.
Infantile-onset spinocerebellar ataxia (IOSCA) is a severe, progressive neurodegenerative disorder characterized by normal development until age one year, followed by onset of ataxia, muscle hypotonia, loss of deep-tendon reflexes, and athetosis. Ophthalmoplegia and sensorineural deafness develop by age seven years. By adolescence, affected individuals are profoundly deaf and no longer ambulatory; sensory axonal neuropathy, optic atrophy, autonomic nervous system dysfunction, and hypergonadotropic hypogonadism in females become evident. Epilepsy can develop into a serious and often fatal encephalopathy: myoclonic jerks or focal clonic seizures that progress to epilepsia partialis continua followed by status epilepticus with loss of consciousness.
Quadriplegia in association with mental retardation, retinitis pigmentosa, and impaired hearing.
Spastic paraplegia-5A is an autosomal recessive neurologic disorder with a wide phenotypic spectrum. Some patients have pure spastic paraplegia affecting only gait, whereas others may have a complicated phenotype with additional manifestations, including optic atrophy or cerebellar ataxia (summary by Arnoldi et al., 2012). The hereditary spastic paraplegias (SPG) are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997). Inheritance is most often autosomal dominant (see 182600), but X-linked (see 303350) and autosomal recessive forms also occur. Genetic Heterogeneity of Autosomal Recessive Spastic Paraplegia Autosomal recessive forms of SPG include SPG7 (607259), caused by mutation in the paraplegin gene (602783) on chromosome 16q24; SPG9B (616586), caused by mutation in the ALDH18A1 gene (138250) on 10q24; SPG11 (604360), caused by mutation in the spatacsin gene (610844) on 15q21; SPG15 (270700), caused by mutation in the ZFYVE26 gene (612012) on 14q24; SPG18 (611225), caused by mutation in the ERLIN2 gene (611605) on 8p11; SPG20 (275900), caused by mutation in the spartin gene (607111) on 13q12; SPG21 (248900), caused by mutation in the maspardin gene (608181) on 15q21; SPG26 (609195), caused by mutation in the B4GALNT1 gene (601873) on 12q13; SPG28 (609340), caused by mutation in the DDHD1 gene (614603) on 14q22; SPG30 (610357), caused by mutation in the KIF1A gene (601255) on 2q37; SPG35 (612319), caused by mutation in the FA2H gene (611026) on 16q23; SPG39 (612020), caused by mutation in the PNPLA6 gene (603197) on 19p13.3; SPG43 (615043), caused by mutation in the C19ORF12 gene (614297) on 19q12; SPG44 (613206), caused by mutation in the GJC2 gene (608803) on 1q42; SPG45 (613162), caused by mutation in the NT5C2 gene (600417) on 10q24; SPG46 (614409), caused by mutation in the GBA2 gene (609471) on 9p13; SPG48 (613647), caused by mutation in the KIAA0415 gene (613653) on 7p22.1; SPG49 (615031) caused by mutation in the TECPR2 gene (615000) on 14q32; SPG54 (615033), caused by mutation in the DDHD2 gene (615003) on 8p11; SPG55 (615035), caused by mutation in the C12ORF65 gene on 12q24; SPG56 (615030), caused by mutation in the CYP2U1 gene (610670) on 4q25; SPG57 (615658), caused by mutation in the TFG gene (602498) on 3q12; SPG61 (615685), caused by mutation in the ARL6IP1 gene (607669) on 1p12; SPG62 (615681), caused by mutation in the ERLIN1 gene on 10q24; SPG63 (615686), caused by mutation in the AMPD2 gene (102771) on 1p13; SPG64 (615683), caused by mutation in the ENTPD1 gene (601752) on 10q24; SPG72 (615625), caused by mutation in the REEP2 gene (609347) on 5q31; SPG74 (616451), caused by mutation in the IBA57 gene (615316) on 1q42; SPG75 (616680), caused by mutation in the MAG gene (159460) on 19q13; SPG76 (616907), caused by mutation in the CAPN1 gene (114220) on 11q13; SPG77 (617046), caused by mutation in the FARS2 gene (611592) on 6p25; SPG78, caused by mutation in the ATP13A2 gene (610513) on 1p36; and SPG79 (615491), caused by mutation in the UCHL1 gene (191342) on 4p13. Additional autosomal recessive forms of SPG have been mapped to chromosomes 3q (SPG14; 605229), 13q14 (SPG24; 607584), 6q (SPG25; 608220), and 10q22 (SPG27; 609041).
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Spastic paraplegia-15 is an autosomal recessive neurodegenerative disorder characterized by progressive spasticity primarily affecting the lower limbs. It is a complex form of spastic paraplegia, associated with other neurologic dysfunction, including variable mental retardation, hearing and visual defects, and thin corpus callosum (summary by Goizet et al., 2009).
A decrease in the ability to perceive vibration in the legs.
ARSACS (autosomal recessive spastic ataxia of Charlevoix-Saguenay) is characterized in individuals born in Quebec Province by early-onset (age 12-18 months) difficulty in walking and gait unsteadiness. In individuals with ARSACS born outside the Province of Quebec, onset is often delayed until later childhood and even adulthood. Ataxia, dysarthria, spasticity, extensor plantar reflexes, distal muscle wasting, a distal sensorimotor neuropathy predominant in the legs, and horizontal gaze-evoked nystagmus constitute the most frequent progressive neurologic signs. Increased demarcation of the retinal nerve fibers located near the vessels close to the optic disc (formerly designated as yellow streaks of hypermyelinated fibers) is very common in individuals with ARSACS who originate from Quebec but may be absent in non-Quebec born individuals. Individuals with ARSACS born in the Province of Quebec become wheelchair bound at the average age of 41 years; cognitive skills are preserved in the long term as individuals remain able to perform daily living tasks late into adulthood. Death commonly occurs in the sixth decade.
Reduced speed of conduction of the action potential along a sensory nerve.
A swan neck deformity describes a finger with a hyperextended PIP joint and a flexed DIP joint. The most common cause for a swan neck-like deformity is a disruption of the end of the extensor tendon. Conditions that loosen the PIP joint and allow it to hyperextend, for example conditions that weaken the volar plate, can produce a swan neck deformity of the finger. One example is rheumatoid arthritis. Another cause are conditions that tighten up the small (intrinsic) muscles of the hand and fingers, for example hand trauma or nerve disorders, such as cerebral palsy, Parkinson's disease, or stroke.
Patients with mutations in the receptor for insulin-like growth factor I show intrauterine growth retardation and postnatal growth failure, resulting in short stature and microcephaly. Other features may include delayed bone age, developmental delay, and dysmorphic features.
Underdevelopment of the frontal lobe of the cerebrum.
A form of gray matter heterotopia were the mislocalized gray matter is typically located periventricularly, also sometimes called subependymal heterotopia. Periventricular means beside the ventricles. This is by far the most common location for heterotopia. Subependymal heterotopia present in a wide array of variations. There can be a small single node or a large number of nodes, can exist on either or both sides of the brain at any point along the higher ventricle margins, can be small or large, single or multiple, and can form a small node or a large wavy or curved mass.
A severe degree of photosensitivity of the skin.
Peeling skin syndrome is a rare genodermatosis with variable age of onset from birth to adulthood. Clinically, it is characterized by a pruritic or nonpruritic spontaneous superficial peeling of the skin, which sometimes is accompanied by erythema or vesiculation. The skin involvement is usually general, but in some patients the scalp, face, palms, and soles may be unaffected. Seasonal changes have been reported. The histologic picture is characterized by separation of the epidermis between the statum corneum and the stratum granulosum (summary by Hacham-Zadeh and Holubar, 1985). Generalized PSS has been subclassified into a noninflammatory type, designated type A, and an inflammatory type, designated type B (Traupe, 1989; Judge et al., 2004). Type B, in which generalized peeling skin is associated with pruritus and atopy, is characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly thereafter. Several patients have been reported with high IgE levels (summary by Oji et al., 2010). Type A, a continuous nonerythematous exfoliation, is usually congenital or appears during childhood (summary by Mallet et al., 2013). Genetic Heterogeneity of Peeling Skin Syndrome Peeling skin syndrome-2 (PSS2; 609796), an acral form of the disorder that mainly involves palmar and plantar skin, is caused by mutation in the TGM5 gene (603805) on chromosome 15q15. Peeling skin syndrome-3 (PSS3; 616265) is caused by mutation in the CHST8 gene (610190) on chromosome 19q13. Peeling skin syndrome-4 (PSS4; 607936) is caused by mutation in the CSTA gene (184600) on chromosome 3q21. Peeling skin syndrome-5 (PSS5; 617115) is caused by mutation in the SERPINB8 gene (601697) on chromosome 18q22. PSS6 (618084) is caused by mutation in the FLG2 gene (616284) on chromosome 1q21.
Lack of transparency of the corneal epithelium.
Abnormally increased hair growth over much of the entire body.
A human hair color characterized by low levels of eumelanin.
A bony peculiarity underlies the Y-shaped fissure of the chin.
ZAP70-related combined immunodeficiency (ZAP70-related CID) is a cell-mediated immunodeficiency caused by abnormal T-cell receptor (TCR) signaling. Affected children usually present in the first year of life with recurrent bacterial, viral, and opportunistic infections, diarrhea, and failure to thrive. Severe lower-respiratory infections and oral candidiasis are common. Affected children usually do not survive past their second year without hematopoietic stem cell transplantation (HSCT).
An abnormality of the physiological functioning of B cells.
Paralysis of the facial nerves on the basis of overgrowth of the cranial bones causing impingement upon the seventh cranial nerve.
Increased density of the bony tissue of the scapula.
Excessive postnatal growth which may comprise increased weight, increased length, and/or increased head circumference.
Increased density of the compact bone of long bone.
The ilia is round and hypoplastic with a very flat acetabular roof and a very unusual medial projection of bone that is said to resemble the head of a snail. Figure 4 of PMID:3799723 illustrates this feature.
Ossification of carpal bones at an abnormally early age.
Precocious (accelerated) maturation and calcification of any of the tarsal bones, seven bones of the foot comprising the calcaneus, talus, cuboid, navicular, and the cuneiform bones.
An abnormally increased width of the cranial fontanelles and sutures.
Absence or underdevelopment of the pubic bone.
An abnormal increase in the bone density of the long bones.
Increased width of the distal part of the shaft (metaphysis) of the femur.
In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits. [HPO:probinson]
Missing radius bone associated with congenital failure of development.
ROR2-related Robinow syndrome is characterized by distinctive craniofacial features, skeletal abnormalities, and other anomalies. Craniofacial features include macrocephaly, broad prominent forehead, low-set ears, ocular hypertelorism, prominent eyes, midface hypoplasia, short upturned nose with depressed nasal bridge and flared nostrils, large and triangular mouth with exposed incisors and upper gums, gum hypertrophy, misaligned teeth, ankyloglossia, and micrognathia. Skeletal abnormalities include short stature, mesomelic or acromesomelic limb shortening, hemivertebrae with fusion of thoracic vertebrae, and brachydactyly. Other common features include micropenis with or without cryptorchidism in males and reduced clitoral size and hypoplasia of the labia majora in females, renal tract abnormalities, and nail hypoplasia or dystrophy. The disorder is recognizable at birth or in early childhood.
Distance between medial and lateral canthi is more than two standard deviations above the mean for age (objective); or, apparently increased length of the palpebral fissures.
The presence of a triangular form of the mouth.
This term applies if one or more of the distal phalanges of the hand are either partially duplicated, depending on severity leading to a broad or bifid appearance of the phalanges, or completely duplicated.
Patients with Richieri-Costa-Pereira syndrome display a pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of the mandible, cleft palate/Robin sequence, absence of lower central incisors, minor ear anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability is also a common finding (summary by Favaro et al., 2011).
An abnormality of the aryepiglottic fold.
Increase in size of the folds of skin between the outer labia.
Absence of fleshy non-cartilaginous tissue inferior to the tragus and incisura.
Slender, slit-like aperture of the nostril.
Increased breadth of the nasal bridge (and with it, the nasal root).
Phocomelia involving all four extremities.
Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis associated with muscle pain and weakness and followed by excretion of myoglobin in the urine. Renal failure may occasionally occur. Onset is usually in early childhood under the age of 5 years. Unlike the exercise-induced rhabdomyolyses such as McArdle syndrome (232600), carnitine palmitoyltransferase deficiency (see 255110), and the Creteil variety of phosphoglycerate kinase deficiency (311800), the attacks in recurrent myoglobinuria no relation to exercise, but are triggered by intercurrent illnesses, commonly upper respiratory tract infections. (Ramesh and Gardner-Medwin, 1992). See 160010 for discussion of a possible autosomal dominant form of myglobinuria. Severe rhabdomyolysis is a major clinical feature of anesthetic-induced malignant hyperthermia (145600), an autosomal dominant disorder.
Longitudinal, linear prominences in the fingernail plate.
A subtype of retinitis pigmentosa in which, instead of the pathology starting in the mid-periphery like typical retinitis pigmentosa, the disease starts in the near periphery closer to the vascular arcades and tends to spare the far periphery.
Syndrome that is characterised by total colour blindness caused by progressive cone dystrophy, degenerative liver disease, and endocrine dysfunction (hypothyroidism, diabetes, repeated abortions or infertility). It has been described in six females from two sibships with a high degree of consanguinity, and in a male from another family.
Reticular pigmentary retinal dystrophy is a form of patterned dystrophy (see MDPT1, 169150) characterized by a reticular pattern of pigmentation that likely appears in infancy and may be fully developed at age 15 years. Indirect funduscopy has shown that the condition is bilateral and symmetric and that the pigmentary deposits are localized below the neuroepithelium, very likely in the pigment epithelium. The reticulum extends from the macula in all directions, sparing the midperiphery and periphery. Visual acuity is unaffected or only minimally affected in advanced stages. Retinal function testing is normal, although the electrooculogram and dark adaptation can be at the lower limit of normal values (summary by Schauwvlieghe et al., 2013).
Mental retardation, hypotonicity, incontinence, muscle atrophy, and inability to walk or speak originally reported in 7 males in 2 generations.
Complete inability of T cells to perform their functions in cell-mediated immunity.
Syndrome with characteristics of renal dysplasia, growth retardation, phocomelia or mesomelia, radiohumeral fusion, rib abnormalities, anomalies of the external genitalia and a potter-like facies. The syndrome has been described in three infants, all of whom died shortly after birth from respiratory distress resulting from pulmonary hypoplasia and oligohydramnios caused by renal dysplasia. The mode of transmission appears to be autosomal recessive.
Two types of melanin, the red pheomelanin and the black eumelanin, are present in human skin. Valverde et al. (1995) noted that eumelanin is photoprotective, whereas pheomelanin may contribute to UV-induced skin damage because of its potential to generate free radicals in response to ultraviolet radiation. Individuals with red hair have a predominance of pheomelanin in hair and skin and/or a reduced ability to produce eumelanin, which may explain why they fail to tan and are at risk from ultraviolet radiation. In mammals, the relative proportions of pheomelanin and eumelanin are regulated by melanocyte-stimulating hormone (see 176830), which acts via its receptor (MC1R) on melanocytes to increase the synthesis of eumelanin, and also via the product of the agouti locus (AGTI; 600201), which antagonizes this action.
RAPADILINO syndrome is a rare condition that involves many parts of the body. Bone development is especially affected, causing many of the characteristic features of the condition.Most affected individuals have underdevelopment or absence of the bones in the forearms and the thumbs, which are known as radial ray malformations. The kneecaps (patellae) can also be underdeveloped or absent. Other features include an opening in the roof of the mouth (cleft palate) or a high arched palate; a long, slender nose; and dislocated joints.Many infants with RAPADILINO syndrome have difficulty feeding and experience diarrhea and vomiting. The combination of impaired bone development and feeding problems leads to slow growth and short stature in affected individuals.Some individuals with RAPADILINO syndrome have harmless light brown patches of skin that resemble a skin finding known as café-au-lait spots. In addition, people with RAPADILINO syndrome have a slightly increased risk of developing a type of bone cancer known as osteosarcoma or a blood-related cancer called lymphoma. In individuals with RAPADILINO syndrome, osteosarcoma most often develops during childhood or adolescence, and lymphoma typically develops in young adulthood.The condition name is an acronym for the characteristic features of the disorder: RA for radial ray malformations, PA for patella and palate abnormalities, DI for diarrhea and dislocated joints, LI for limb abnormalities and little size, and NO for slender nose and normal intelligence.The varied signs and symptoms of RAPADILINO syndrome overlap with features of other disorders, namely Baller-Gerold syndrome and Rothmund-Thomson syndrome. These syndromes are also characterized by radial ray defects, skeletal abnormalities, and slow growth. All of these conditions can be caused by mutations in the same gene. Based on these similarities, researchers are investigating whether Baller-Gerold syndrome, Rothmund-Thomson syndrome, and RAPADILINO syndrome are separate disorders or part of a single syndrome with overlapping signs and symptoms.
An increased concentration of pyruvate in the blood.
Deficiency of pyrimidine 5-prime nucleotidase, also called uridine 5-prime monophosphate hydrolase, causes an autosomal recessive hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. The enzyme is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. Hirono et al. (1988) suggested that this deficiency is the third most common RBC enzymopathy--after G6PD (300908) and pyruvate kinase (see 266200) deficiencies--causing hemolysis (summary by Marinaki et al., 2001).
Pyridoxine-dependent epilepsy is characterized by intractable seizures within the first weeks to months of life that are not controlled with antiepileptic drugs but respond both clinically and electrographically to large daily supplements of pyridoxine (vitamin B6). Multiple types of clinical seizures have been reported in individuals with pyridoxine-dependent epilepsy. Dramatic presentations consisting of prolonged seizures and recurrent episodes of status epilepticus are typical; recurrent self-limited events including partial seizures, generalized seizures, atonic seizures, myoclonic events, and infantile spasms also occur. Affected individuals may have electrographic seizures without clinical correlates. Infants with the classic neonatal presentation begin to experience seizures soon after birth. Atypical features include: late-onset seizures (seizures that begin from late infancy up until age 3 years); seizures that initially respond to antiepileptic drugs and then become intractable; seizures during early life that do not respond to pyridoxine but are then controlled with pyridoxine several months later; and prolonged seizure-free intervals (=5.5 months) that occur after discontinuation of pyridoxine. Intellectual disability is common. Elevated concentration of a-aminoadipic semialdehyde (a-AASA) in urine and plasma is a strong biomarker of the disorder; pipecolic acid may also be elevated in plasma and cerebrospinal fluid.
Pyknoachondrogenesis is a lethal skeletal osteochondrodysplasia characterised by severe generalised osteosclerosis. The disease is very rare and only five cases (four males and one female) have been reported in the literature so far. Pyknoachondrogenesis may be detected prenatally due to the extreme shortening of the limbs and hydrops fetalis, or is recognised at birth. The main clinical manifestations include a large head, palpebral oedema, a flat nose, low-set ears, a short neck, a short and wide trunk, a prominent abdomen, and severe micromelic dwarfism. Aetiology remains unknown. Pyknoachondrogenesis has a lethal outcome, either prenatally or during the early neonatal period.
The anterior fontanelle generally ossifies by around the 18th month of life. A persistent open anterior fontanelle is diagnosed if closure is delayed beyond this age.
Delayed tooth eruption affecting the primary dentition.
Delayed tooth eruption affecting the secondary dentition.
A congenital abnormality in the lungs characterized by the presence of dilated lymphatic vessels in the interlobar, perivascular, and peribronchial areas of the lungs. Signs and symptoms appear at birth and include tachypnea, cyanosis, and respiratory distress.
Anterior schisis (cleft or cleavage) of vertebral bodies.
Atherosclerosis which occurs in a person with certain risk factors (e.g., SLE, diabetes, smoking, hypertension, hypercholesterolaemia, family history of early heart disease) at an earlier age than would occur in another person without those risk factors.
A very rare disorder associating pseudopapilledema (optic disc swelling not secondary to increased intracranial pressure) mixed hearing loss, facial dysmorphism and limb extremity anomalies. Only 4 cases have been reported in the literature from 3 inbred sibships. The affected patients have no intellectual deficit. Transmitted as an autosomal recessive trait.
Increased distance between the attachments of the alae nasi to the face.
Peroxisomal acyl-CoA oxidase deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also D-bifunctional protein deficiency (261515), caused by mutation in the HSD17B4 gene (601860) on chromosome 5q2. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (see 601539) (Watkins et al., 1995).
Any abnormality of the electrical responses of various cell types in the retina as measured by electroretinography.
Progesterone prepares the endometrium for blastocyst implantation and allows maintenance of pregnancy. The major sources of progesterone are the corpus luteum during the second half of the menstrual cycle and at the beginning of pregnancy, and the placenta. The main hormones responsible for stimulation of progesterone secretion are luteinizing hormone (LH) for the corpus luteum of the menstrual cycle and chorionic gonadotropin for the corpus luteum of pregnancy. Complete end-organ resistance to progesterone would be incompatible with reproductive competence in females. Males would not be expected to be affected since progesterone has no known function in men. Failure of the uterus to respond to progesterone would lead to the development of a 'constantly proliferative' endometrium incompatible with blastocyst implantation. Partial resistance to progesterone, on the other hand, would be expected to be associated with various degrees of incomplete maturation of the endometrium, perhaps expressed clinically as infertility or early abortions. The syndrome would present with the clinical and histologic picture of a luteal phase defect in which the life span of the corpus luteum and the plasma progesterone concentrations would be normal or elevated.
Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) D is an autosomal recessive disorder characterized by mild transient hyperphenylalaninemia often detected by newborn screening. Patients also show increased excretion of 7-biopterin. Affected individuals are asymptomatic and show normal psychomotor development, although transient neurologic deficits in infancy have been reported (Thony et al., 1998). Patients may also develop hypomagnesemia and nonautoimmune diabetes mellitus during puberty (summary by Ferre et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of BH4-deficient hyperphenylalaninemia, see HPABH4A (261640).
Bartsocas-Papas syndrome (lethal popliteal pterygium syndrome) is an autosomal recessive disorder characterized by multiple popliteal pterygia, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and syndactyly. Early lethality is common, although survival into childhood and beyond has been reported (summary by Mitchell et al., 2012). A less severe form of popliteal pterygium syndrome (119500) is caused by mutation in the IRF6 gene (607199).
Syndrome with characteristics of polysyndactyly, hexadactyly (duplication of the first toe) and complex cardiac malformation (including atrial and ventricular septal defect, single ventricle, aortic dextroposition, or dilation of the right heart). It has been described in six patients from three unrelated families. Other manifestations were present in some patients (i.e. facial dysmorphism, hepatic cysts).
Adult polyglucosan body disease (APBD) is characterized by adult-onset progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities, and mild cognitive difficulties (often executive dysfunction).
Underdevelopment of the helix that either affects the entire helix, or is localized.
Gillessen-Kaesbach-Nishimura syndrome is an autosomal recessive multiple congenital anomaly disorder characterized by skeletal dysplasia, dysmorphic facial features, and variable visceral abnormalities, including polycystic kidneys, diaphragmatic hernia, lung hypoplasia, and congenital heart defects. It may be lethal in utero or early in life. The disorder is at the severe end of the phenotypic spectrum of congenital disorders of glycosylation (summary by Tham et al., 2016).
A lack of differentiation between renal cortex and medulla on diagnostic imaging.
The presence of fibrosis affecting the interlobular stroma of liver.
Kowarski syndrome, or short stature associated with bioinactive growth hormone, is characterized clinically by normal or slightly increased GH secretion, pathologically low IGF1 (147440) levels, and normal catch-up growth on GH replacement therapy (Besson et al., 2005).
Chronic degenerative changes of the teeth, mainly the incisors, due to trauma or inflammation. It involves abnormal development of odontogenic tissue and is characterized by abnormal deposits of dentin, cementum, and osteoid.
A very rare syndrome with the association of limb pterygia, heart anomalies, autosomal recessive inheritance, vertebral defects, ear anomalies and radial defects. It has been described in two siblings. One of the siblings also had a myelomeningocele. The reported cases suggest the condition is hereditary with probable autosomal recessive inheritance.
A very rare dysmorphic syndrome described in two siblings. The syndrome has characteristics of short stature, unique facies, enamel hypoplasia, progressive joint stiffness, high-pitched voice, cup-shaped ears and narrow palpebral fissures with epicanthal folds and intellectual deficit.
The persistent mullerian duct syndrome is characterized by the persistence of mullerian derivatives, uterus and tubes, in otherwise normally virilized males (summary by Knebelmann et al., 1991).
A type of disproportionate short stature characterized by a short limbs but an average-sized trunk.
Agenesis of one or more maxillary lateral incisor, comprising the maxillary lateral primary incisor and maxillary lateral secondary incisor.
An abnormally squared appearance of the bony pelvis, a normally rounded or basin-shaped structure.
An abnormal punctate (speckled, dot-like) pattern of calcifications in soft tissues within or surrounding bones (as observed on radiographs).
Eosinophil peroxidase deficiency is a rare abnormality of eosinophil granulocytes characterized by decreased or absent peroxidase activity and decreased volume of the granule matrix (summary by Romano et al., 1994). Nakagawa et al. (2001) noted that there are no clinical symptoms and the diagnosis is made solely by cytochemical analysis.
Syndrome with characteristics of pelviscapular dysplasia with epiphyseal abnormalities, congenital dwarfism and facial dysmorphism. The facial dysmorphism has manifestations of frontal bossing, hypertelorism, narrow palpebral fissures, deep-set eyes, strabismus, low-set posteriorly rotated and malformed ears, dysplasia of conchae, a small chin, a short neck with redundant skin folds, and a low hairline. Intelligence may vary from normal to moderately impaired. Radiographic features comprise aplasia of the body of the scapula, hypoplasia of the iliac bone, humeroradial synostosis, dislocation of the femoral heads, and moderate brachydactyly. Mutations in the TBX15 gene have been identified as potentially causative. Pelviscapular dysplasia is phenotypically similar to pelvis-shoulder dysplasia.
Absence of the proximal interphalangeal flexion creases of the fingers.
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Autosomal recessive hypomyelinating leukodystrophy-3 (HLD3) is a severe neurologic disorder characterized by early infantile onset of global developmental delay, lack of development, lack of speech acquisition, and peripheral spasticity associated with decreased myelination in the central nervous system (summary by Feinstein et al., 2010). The disorder is phenotypically similar to X-linked Pelizaeus-Merzbacher disease (PMD; 312080), which is caused by mutation in the PLP1 gene (300401). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080.
PEHO is a severe autosomal recessive neurodevelopmental disorder characterized by extreme cerebellar atrophy due to almost total loss of granule neurons. Affected individuals present in early infancy with hypotonia, profoundly delayed psychomotor development, optic atrophy, progressive atrophy of the cerebellum and brainstem, and dysmyelination. Most patients also develop infantile seizures that are often associated with hypsarrhythmia on EEG, and many have peripheral edema (summary by Anttonen et al., 2017).
Triangular appearance of the oral aperture with the apex in the midpoint of the upper vermilion and the lower vermilion forming the base.
A rare disorder characterized by rigid, thick skin that covers the entire body and affects movements. The movement of the chest and abdomen is severely restricted. Affected individuals develop respiratory insufficiency which may lead to death.
The sacroiliac joint in the bony pelvis connects the sacrum and the ilium of the pelvis, which are joined by strong ligaments. The notch is located directly superior to the joint. This term refers to a reduction in the lateral dimension of the notch.
Partial agenesis of the pancreas is characterized by the congenital absence of a critical mass of pancreatic tissue.
Raine syndrome is a neonatal osteosclerotic bone dysplasia of early and aggressive onset that usually results in death within the first few weeks of life, although there have been some reports of survival into childhood. Radiographic studies show a generalized increase in the density of all bones and a marked increase in the ossification of the skull. The increased ossification of the basal structures of the skull and facial bones underlies the characteristic facial features, which include narrow prominent forehead, proptosis, depressed nasal bridge, and midface hypoplasia. Periosteal bone formation is also characteristic of this disorder and differentiates it from osteopetrosis and other known lethal and nonlethal osteosclerotic bone dysplasias. The periosteal bone formation typically extends along the diaphysis of long bones adjacent to areas of cellular soft tissue (summary by Simpson et al., 2009).
Osteopetrosis (OPT) is a life-threatening disease caused by subnormal osteoclast function, with an incidence of 1 in 250,000 births. The disease usually manifests in the first few months of life with macrocephaly and frontal bossing, resulting in a characteristic facial appearance. Defective bone remodeling of the skull results in choanal stenosis with concomitant respiratory problems and feeding difficulties, which are the first clinical manifestation of disease. The expanding bone encroaches on neural foramina, leading to blindness, deafness, and facial palsy. Complete visual loss invariably occurs in all untreated patients, and hearing loss is estimated to affect 78% of patients with OPT. Tooth eruption defects and severe dental caries are common. Calcium feedback hemostasis is impaired, and children with OPT are at risk of developing hypocalcemia with attendant tetanic seizures and secondary hyperparathyroidism. The most severe complication of OPT, limiting survival, is bone marrow insufficiency. The abnormal expansion of cortical and trabecular bone physically limits the availability of medullary space for hematopoietic activity, leading to life-threatening cytopenia and secondary expansion of extramedullary hematopoiesis at sites such as the liver and spleen (summary by Aker et al., 2012). Genetic Heterogeneity of Autosomal Recessive Osteopetrosis Other forms of autosomal recessive infantile malignant osteopetrosis include OPTB4 (611490), which is caused by mutation in the CLCN7 gene (602727) on chromosome 16p13, and OPTB5 (259720), which is caused by mutation in the OSTM1 gene (607649) on chromosome 6q21. A milder, osteoclast-poor form of autosomal recessive osteopetrosis (OPTB2; 259710) is caused by mutation in the TNFSF11 gene (602642) on chromosome 13q14, an intermediate form (OPTB6; 611497) is caused by mutation in the PLEKHM1 gene (611466) on chromosome 17q21, and a severe osteoclast-poor form associated with hypogammaglobulinemia (OPTB7; 612301) is caused by mutation in the TNFRSF11A gene (603499) on chromosome 18q22. Another form of autosomal recessive osteopetrosis (OPTB8; 615085) is caused by mutation in the SNX10 gene (614780) on chromosome 7p15. A form of autosomal recessive osteopetrosis associated with renal tubular acidosis (OPTB3; 259730) is caused by mutation in the CA2 gene (611492) on chromosome 8q21. Autosomal dominant forms of osteopetrosis are more benign (see OPTA1, 607634).
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones.
A rare syndrome described in two sisters of Mennonite descent, with characteristics of sparse hair, osteopenia, intellectual disability, minor facial abnormalities, joint laxity and hypotonia. There have been no further descriptions in the literature since 1992.
Multicentric osteolysis nodulosis and arthropathy (MONA) is a skeletal dysplasia characterized by progressive osteolysis (particularly of the carpal and tarsal bones), osteoporosis, subcutaneous nodules on the palms and soles, and progressive arthropathy (joint contractures, pain, swelling, and stiffness). Other manifestations include coarse facies, pigmented skin lesions, cardiac defects, and corneal opacities. Onset is usually between ages six months and six years (range: birth to 11 years).
Bruck syndrome is characterized by congenital contractures with pterygia, onset of fractures in infancy or early childhood, postnatal short stature, severe limb deformity, and progressive scoliosis (McPherson and Clemens, 1997). Genetic Heterogeneity of Bruck Syndrome Bruck syndrome-2 (609220) is caused by homozygous mutation in the PLOD2 gene (601865) on chromosome 3q24. Van der Slot et al. (2003) stated that they were unaware of any phenotypic differences between the 2 forms of Bruck syndrome.
Osteogenesis imperfecta is a connective tissue disorder characterized clinically by bone fragility and increased susceptibility to fractures. Osteogenesis imperfecta type IX is a severe autosomal recessive form of the disorder (summary by van Dijk et al., 2009).
A type of short-limbed dwarfism that is manifest beginning in the neonatal period.
Curvature of the shafts of the long bones due to multiple fractures.
A polar cataract that affects the posterior pole of the lens.
An excessive concavity of the posterior surface of one or more vertebral bodies.
A type of cleft lip presenting as a midline (median) gap in the upper lip.
Underdevelopment (reduced size) of the tibia.
Total ophthalmoplegia involves total paralysis of all extra- and intraocular muscles. If one or more of the external muscles, including the levator palpebrae, is not affected, the condition is known as incomplete or partial ophthalmoplegia. If only 1 nerve is affected, the palsy is named after that nerve (see, e.g., abducens palsy, 100200) (Waardenburg, 1963).
Syndrome with the association of omphalocele and cleft palate. It has been described in three daughters of normal unrelated parents. They were all diagnosed at birth. This syndrome is likely to be inherited as an autosomal recessive condition.
Omodysplasia-1 (OMOD1) is a rare autosomal recessive skeletal dysplasia characterized by severe congenital micromelia with shortening and distal tapering of the humeri and femora to give a club-like appearance. Typical facial features include a prominent forehead, frontal bossing, short nose with a depressed broad bridge, short columella, anteverted nostrils, long philtrum, and small chin. Variable findings are cryptorchidism, hernias, congenital heart defects, and cognitive delay (Elcioglu et al., 2004; Albano et al., 2007). Genetic Heterogeneity of Omodysplasia In an autosomal dominant form of omodysplasia (OMOD2; 164745), abnormalities are limited to the upper limbs. The facial changes and typical growth defect of the distal humerus with complex deformity of the elbows appear to be similar in both entities (Baxova et al., 1994).
A very rare syndrome with characteristics of intellectual deficit, postaxial polydactyly and epilepsy. To date, seven individuals in three families have been reported. Facial features are not characteristic except for a prominent jaw. Concordant features in all subjects are postaxial polydactyly, which in four individuals affect also the feet, and intellectual deficit, which is usually severe, with absent or indistinct speech. Seizures are common with onset in the first months of life or in early childhood. Cutaneous syndactyly, camptodactyly and clinodactyly of fingers and brachydactyly and syndactyly of the toes have been recorded.
A rare combination of congenital abnormalities that includes omphalocele, cloacal exstrophy, imperforate anus, and spine abnormalities.
This disease has characteristics of retinitis pigmentosa, trichodysplasia, dental anomalies, and onychodysplasia. It has been described in two siblings (brother and sister) born to first cousin parents. Transmission appears to be autosomal recessive.
Presence of only one (instead of two, as normal) interphalangeal crease of the fifth finger.
Oculopalatocerebral syndrome is a rare disorder characterized by low birth weight, microcephaly, persistent hyperplastic primary vitreous, microphthalmia, large ears, small hands and feet, cleft palate, joint hypermobility, developmental delay, and cerebral atrophy (summary by Pellegrino et al., 2001).
Mosaic variegated aneuploidy (MVA) syndrome is a rare disorder in which some cells in the body have an abnormal number of chromosomes instead of the usual 46 chromosomes, a situation known as aneuploidy. Most commonly, cells have an extra chromosome, which is called trisomy, or are missing a chromosome, which is known as monosomy. In MVA syndrome, some cells are aneuploid and others have the normal number of chromosomes, which is a phenomenon known as mosaicism. Typically, at least one-quarter of cells in affected individuals have an abnormal number of chromosomes. Because the additional or missing chromosomes vary among the abnormal cells, the aneuploidy is described as variegated.In MVA syndrome, growth before birth is slow (intrauterine growth restriction). After birth, affected individuals continue to grow at a slow rate and are shorter than average. In addition, they typically have an unusually small head size (microcephaly). Another common feature of MVA syndrome is an increased risk of developing cancer in childhood. Cancers that occur most frequently in affected individuals include a cancer of muscle tissue called rhabdomyosarcoma, a form of kidney cancer known as Wilms tumor, and a cancer of the blood-forming tissue known as leukemia.Less commonly, people with MVA syndrome have eye abnormalities or distinctive facial features, such as a broad nasal bridge and low-set ears. Some affected individuals have brain abnormalities, the most common of which is called Dandy-Walker malformation. Intellectual disability, seizures, and other health problems can also occur in people with MVA syndrome.There are at least three types of MVA syndrome, each with a different genetic cause. Type 1 is the most common and displays the classic signs and symptoms described above. Type 2 appears to have slightly different signs and symptoms than type 1, although the small number of affected individuals makes it difficult to define its characteristic features. Individuals with MVA syndrome type 2 grow slowly before and after birth; however, their head size is typically normal. Some people with MVA syndrome type 2 have unusually short arms. Individuals with MVA syndrome type 2 do not seem to have an increased risk of cancer. Another form of MVA syndrome is characterized by a high risk of developing Wilms tumor. Individuals with this form may also have other signs and symptoms typical of MVA syndrome type 1.
Autosomal recessive congenital stationary night blindness is a disorder of the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing and distinguishing objects in low light (night blindness). For example, they may not be able to identify road signs at night or see stars in the night sky. They also often have other vision problems, including loss of sharpness (reduced acuity), nearsightedness (myopia), involuntary movements of the eyes (nystagmus), and eyes that do not look in the same direction (strabismus).The vision problems associated with this condition are congenital, which means they are present from birth. They tend to remain stable (stationary) over time.
Giant axonal neuropathy (GAN) is an early-onset fatal neurodegenerative disorder. GAN starts as severe peripheral motor and sensory neuropathy during infancy and evolves into central nervous system impairment (intellectual disability, seizures, cerebellar signs, and pyramidal tract signs). Most individuals become wheelchair dependent in the second decade of life and eventually bedridden with severe polyneuropathy, ataxia, and dementia. Death usually occurs in the third decade.
MPV17-related mitochondrial DNA (mtDNA) maintenance defect presents in the vast majority of affected individuals as an early-onset encephalohepatopathic (hepatocerebral) disease that is typically associated with mtDNA depletion, particularly in the liver. A later-onset neuromyopathic disease characterized by myopathy and neuropathy, and associated with multiple mtDNA deletions in muscle, has also rarely been described. MPV17-related mtDNA maintenance defect, encephalohepatopathic form is characterized by: Hepatic manifestations (liver dysfunction that typically progresses to liver failure, cholestasis, hepatomegaly, and steatosis); Neurologic involvement (developmental delay, hypotonia, microcephaly, and motor and sensory peripheral neuropathy); Gastrointestinal manifestations (gastrointestinal dysmotility, feeding difficulties, and failure to thrive); and Metabolic derangements (lactic acidosis and hypoglycemia). Less frequent manifestations include renal tubulopathy, nephrocalcinosis, and hypoparathyroidism. Progressive liver disease often leads to death in infancy or early childhood. Hepatocellular carcinoma has been reported.
Repeated occurrences of acute noninflammatory encephalopathy and fatty degenerative liver failure.
A form of hepatic steatosis characterized by the presence of small, lipid-laden vesicles in the affected hepatocytes.
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment patterns observed most often in CLN5 comprise mixed combinations of 'granular,' 'curvilinear,' and 'fingerprint' profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
An intracellular accumulation of autofluorescent lipopigment storage material in a straight or rectilinear pattern.
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment pattern seen most often in CLN1 is referred to as granular osmiophilic deposits (GROD). The patterns most often observed in CLN2 and CLN3 are 'curvilinear' and 'fingerprint' profiles, respectively. CLN4, CLN5, CLN6, CLN7, and CLN8 show mixed combinations of granular, curvilinear, fingerprint, and rectilinear profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). Zeman and Dyken (1969) referred to these conditions as the 'neuronal ceroid lipofuscinoses.' Goebel (1995) provided a comprehensive review of the NCLs and noted that they are possibly the most common group of neurodegenerative diseases in children. Mole et al. (2005) provided a detailed clinical and genetic review of the neuronal ceroid lipofuscinoses. Genetic Heterogeneity of Neuronal Ceroid Lipofuscinosis See also CLN2 (204500), caused by mutation in the TPP1 gene (607998) on chromosome 11p15; CLN3 (204200), caused by mutation in the CLN3 gene (607042) on 16p12; CLN4A (204300), caused by mutation in the CLN6 gene (606725) on 15q21; CLN4B (162350), caused by mutation in the DNAJC5 gene (611203) on 20q13; CLN5 (256731), caused by mutation in the CLN5 gene (608102) on 13q; CLN6 (601780), caused by mutation in the CLN6 gene (602780) on 15q21; CLN7 (610951), caused by mutation in the MFSD8 gene (611124) on 4q28; CLN8 (600143) and the Northern epilepsy variant of CLN8 (610003), caused by mutation in the CLN8 gene (607837) on 8pter; CLN10 (610127), caused by mutation in the CTSD gene (116840) on 11p15; CLN11 (614706), caused by mutation in the GRN gene (138945) on 17q; CLN13 (615362), caused by mutation in the CTSF gene (603539) on 11q13; and CLN14 (611726), caused by mutation in the KCTD7 gene (611725) on 7q11. CLN9 (609055) has not been molecularly characterized. A disorder that was formerly designated neuronal ceroid lipofuscinosis-12 (CLN12) is now considered to be a variable form of Kufor-Rakeb syndrome (KRS; 606693).
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Generalized abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Dehydration resulting from abnormally high levels of sodium in the blood. Infants and individuals that are intubated are at highest risk.
Clinical features of atelosteogenesis type 2 (AO2) include rhizomelic limb shortening with normal-sized skull, hitchhiker thumbs, small chest, protuberant abdomen, cleft palate, and distinctive facial features (midfaceretrusion, depressed nasal bridge, epicanthus, micrognathia). Other typical findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot. AO2 is lethal at birth or shortly thereafter because of pulmonary hypoplasia and tracheobronchomalacia.
This autosomal recessive systemic autoinflammatory disorder is characterized by early childhood onset of annular erythematous plaques on the face and extremities with subsequent development of partial lipodystrophy and laboratory evidence of immune dysregulation. More variable features include recurrent fever, severe joint contractures, muscle weakness and atrophy, hepatosplenomegaly, basal ganglia calcifications, and microcytic anemia (summary by Agarwal et al., 2010; Kitamura et al., 2011; Arima et al., 2011). This disorder encompasses Nakajo-Nishimura syndrome (NKJO); joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome); and chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE). Among Japanese patients, this disorder is best described as Nakajo-Nishimura syndrome, since both Nakajo (1939) and Nishimura et al. (1950) contributed to the original phenotypic descriptions. Genetic Heterogeneity of Proteasome-Associated Autoinflammatory Syndrome See also PRAAS2 (618048), caused by mutation in the POMP gene (613386) on chromosome 13q12, and PRAAS3 (617591), caused by mutation in the PSMB4 gene (602177) on chromosome 1q21.
Asthenic habitus refers to a slender build with long limbs, an angular profile, and prominent muscles or bones.
Bailey-Bloch congenital myopathy, also known as Native American myopathy (NAM), is an autosomal recessive disorder characterized by congenital weakness and arthrogryposis, cleft palate, ptosis, myopathic facies, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia provoked by anesthesia. It was first reported in the Lumbee Indian tribe in North Carolina (summary by Stamm et al., 2008).
Nathalie syndrome has characteristics of deafness, cataract, muscular atrophy, skeletal abnormalities, growth retardation, underdeveloped secondary sexual characteristics and electrocardiographic abnormalities. It has been described in a Dutch family: in three sisters (one named Nathalie) and their brother.
Keipert syndrome is characterized by brachydactyly, broad thumbs and halluces, hypertelorism and other minor facial dysmorphic features, and sensorineural deafness. Phenotypically related syndromes include Teunissen-Cremers syndrome (184460), Muenke syndrome (602849) and Keutel syndrome (245150) (Nik-Zainal et al., 2008).
More pronounced paramedian peaks and median notch of the Cupid's bow.
Abnormally wide (broad) distal phalanx of finger.
An abnormal flattening of an epiphysis of femur.
An abnormal anterior curvature of a long bone.
Muscle hypertrophy primarily affecting the legs.
Multiminicore disease (MMD) is an inherited neuromuscular disorder defined pathologically by the presence of multiple areas of reduced mitochondrial oxidative activity running along a limited extent of the longitudinal axis of the muscle fiber, so-called 'minicores.' These regions show sarcomere disorganization and mitochondria depletion. Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present. MMD is a pathologic diagnosis and shows clinical and genetic heterogeneity. Affected individuals have clinical features of a congenital myopathy, including neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy, which may progress slowly or remain stable (Ferreiro and Fardeau, 2002). Patients with recessive mutations in the RYR1 gene typically show severe congenital muscular dystrophy with ophthalmoplegia, although there is phenotypic variability. Some patients may present in utero with fetal akinesia, arthrogryposis, and lung hypoplasia resulting in fetal or perinatal death (McKie et al., 2014). Skeletal muscle biopsy of patients with recessive RYR1 mutations show variable features, including central cores (Jungbluth et al., 2007), congenital fiber-type disproportion (CFTD) (Monnier et al., 2009), and centronuclear myopathy (Wilmshurst et al., 2010).
Myopathy with deficiency of ISCU, a mitochondrial myopathy, is classically characterized by lifelong exercise intolerance in which minor exertion causes tachycardia, shortness of breath, fatigue, and pain of active muscles; episodes of more profound exercise intolerance associated with rhabdomyolysis, myoglobinuria, and weakness that may be severe; and typically full recovery of muscle strength between episodes of rhabdomyolysis. Affected individuals usually have near-normal strength; they can have large calves.
Recurrent episodes of brain dysfunction that may be triggered by factors such as metabolic disturbances or infections.
Carey-Fineman-Ziter syndrome (CFZS) is a multisystem congenital disorder characterized by hypotonia, Moebius sequence (bilateral congenital facial palsy with impairment of ocular abduction), Pierre Robin complex (micrognathia, glossoptosis, and high-arched or cleft palate), delayed motor milestones, and failure to thrive. More variable features include dysmorphic facial features, brain abnormalities, and intellectual disability. It has been postulated that many clinical features in CFZS may be secondary effects of muscle weakness during development or brainstem anomalies (summary by Pasetti et al., 2016). Di Gioia et al. (2017) determined that CFZS represents a slowly progressive congenital myopathy resulting from a defect in myoblast fusion.
A type of focal seizure (i.e., affecting initially only one hemisphere of the brain) that is simple (not resulting in alteration of consciousness) that originates in the occipital lobe. Visual hallucinations are the hallmark of occipital seizures, but are not invariably present. Hallucinations typically commence in the visual field contralateral to the affected visual cortex and then spread to involve the entire visual field. Elementary visual seizures are characterized by fleeting visual manifestations which may be either positive (flashes, phosphenes) or, less commonly, negative (scotoma, hemianopia, amaurosis). Positive phenomena are usually flashes of colour or light, which are simple in shape and may be static or mobile.
A decreased alkaline phosphatase activity measured within leukocytes.
Amyotrophy (muscular atrophy) affecting the proximal musculature.
Dysferlinopathy includes a spectrum of muscle disease characterized by two main phenotypes: Miyoshi myopathy with primarily distal weakness and limb-girdle muscular dystrophy type 2B (LGMD2B) with primarily proximal weakness. Miyoshi myopathy (median age of onset 19 years) is characterized by muscle weakness and atrophy, most marked in the distal parts of the legs, especially the gastrocnemius and soleus muscles. Over a period of years, the weakness and atrophy spread to the thighs and gluteal muscles. The forearms may become mildly atrophic with decrease in grip strength; the small muscles of the hands are spared. LGMD2B is characterized by early weakness and atrophy of the pelvic and shoulder girdle muscles in adolescence or young adulthood, with slow progression. Other phenotypes are scapuloperoneal syndrome, distal myopathy with anterior tibial onset, elevated serum CK concentration only, and congenital muscular dystrophy.
The occurrence of an unusually high amount of muscle pain following exercise.
The clinical manifestations of LAMA2-related muscular dystrophy (LAMA2 MD) range from severe, early-onset congenital muscular dystrophy (CMD) – referred to as early-onset LAMA2-related muscular dystrophy (LAMA2 MD) in this GeneReview – to mild, later childhood-onset limb-girdle type muscular dystrophy – referred to here as late-onset LAMA2-related muscular dystrophy (LAMA2 MD). Children with early-onset LAMA2 MD have profound hypotonia with muscle weakness evident at birth or within the first six months of life, poor spontaneous movements with contractures of the large joints, and weak cry often associated with respiratory failure. Feeding difficulties with failure to thrive, aspiration, and recurrent chest infections are typical. Progressive scoliosis starting in childhood is common. Seizures and, less often, cardiac involvement can occur. Typically, individuals with early-onset LAMA2 MD do not achieve independent ambulation. Intellect is usually normal. Those with limb-girdle type muscular dystrophy have later onset of proximal muscle weakness and delayed motor milestones, but achieve independent ambulation; they may develop a rigid spine syndrome with joint contractures. Progressive respiratory insufficiency and scoliosis can occur.
Abnormal cell death involving muscle fibers usually associated with break in, or absence of, muscle surface fiber membrane and resulting in irreversible damage to muscle fibers.
The ability of the wrist joints to move beyond their normal range of motion.
Sorsby fundus dystrophy is an autosomal dominant retinal dystrophy characterized by the loss of central vision as a result of macular disease by the fourth to fifth decade and peripheral visual loss in late life (summary by Wijesuriya et al., 1996).
Fuchs endothelial corneal dystrophy (FECD) is a progressive, bilateral condition characterized by dysfunction of the corneal epithelium, leading to reduced vision. The prevalence of FECD has been estimated at about 5% among persons over the age of 40 years in the United States. The vision loss in patients with FECD results from a loss of corneal transparency associated with irregularity of inner corneal layers in early disease and edema of the cornea in advanced disease. Ultrastructural features of FECD include loss and attenuation of endothelial cells, with thickening and excrescences of the underlying basement membrane. These excrescences, called guttae, are the clinical hallmark of FECD and become more numerous with progression of the disease. As the endothelial layer develops confluent guttae in the central cornea, the cells are no longer able to keep the cornea dehydrated and clear (summary by Baratz et al., 2010). Genetic Heterogeneity of Fuchs Endothelial Corneal Dystrophy More common, late-onset forms of FECD have been shown to be caused by mutation in the SLC4A11 gene (610206) on chromosome 20p13 (FECD4; 613268), in the ZEB1 gene (189909) on chromosome 10p11.2 (FECD6; 613270), and in the AGBL1 gene (615496) on chromosome 15q25 (FECD8; 615523). Other loci for late-onset FECD have been identified on chromosomes 13pter-q12.13 (FECD2; 610158), 18q21.2-q21.32 (FECD3; 613267), 5q33.1-q35.2 (FECD5; 613269), and 9p (FECD7; 613271).
Cleft palate of the midline of the palate.
Presence of a cutaneous lipoma on the forehead.
A severe delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts.
Abnormally increased hair growth in the lumbosacral region.
A hand or foot with more than five digits that has a recognizable A/P axis of symmetry. The axis can lie within a normally formed or partially duplicated digit resembling a middle finger, index finger, thumb, toe, or hallux. Alternatively, the axis can be in an interdigital space with a flanking pair of digits that resemble a middle finger, index finger, thumb, toe or hallux. The most lateral digits on each side of the hand typically resemble fifth fingers/toes.
Atrophy of the levator palpebrae superioris, the extraocular muscle that elevates the superior eyelid.
Atrophy of the superior rectus, the extraocular muscle whose primary function is to elevate the globe.
This syndrome has characteristics of gingival fibromatosis associated with progressive sensorineural hearing loss. It has been described in two families (with at least 16 affected members spanning five generations in one of the families and five affected members spanning three generations in the other family). It is transmitted as an autosomal dominant trait.
An abnormal localized widening (dilatation) of the aortic arch.
Extreme hirsutism with gingival fibromatosis follows a dominant pattern of inheritance (Weski, 1920; Garn and Hatch, 1950). There is no necessary relationship between the age of development of the gingival changes and the hypertrichosis. The latter may be present at birth but often appears at puberty (Anderson et al., 1969). For a discussion of genetic heterogeneity of congenital generalized hypertrichosis, see HTC1 (145701).
Hereditary desmoid disease usually presents as an extraintestinal manifestation of familial adenomatous polyposis (FAP; 175100), also known as Gardner syndrome, which is an autosomal dominant disorder caused by germline mutation in the APC gene. The desmoid tumors are usually intraabdominal and, although benign, can be locally aggressive and result in significant morbidity. Desmoid tumors can also arise sporadically (Couture et al., 2000).
An abnormality of the renal collecting system.
A developmental defect of the sacrum characterized by partial or disordered development of the sacrum in which portions of the sacrum, which normally is formed by fusion of five sacral vertebrae S1-S5, fail to form or fail to form normally.
Absence or underdevelopment of the femur.
A limitation of the range of movement of the shoulder joint.
Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is characterized by failure of peripheral retinal vascularization. The visual problems and variable phenotype associated with adFEVR result from secondary complications caused by retinal ischemia. The retinal avascularity is probably present from birth and generates sequelae that stabilize in early adult life or progress in later life. Expressivity may be asymmetric and is highly variable, ranging from mild or asymptomatic to severe (e.g., registered as blind) within the same family.
The presence of multiple exostoses on the scapula. An exostosis is a benign growth the projects outward from the bone surface. It is capped by cartilage.
The presence of multiple protuberances (bulges, or knobs) at the ends of the long bones.
Cerebrooculofacioskeletal syndrome is a severe, progressive neurologic disorder characterized by prenatal onset of arthrogryposis, microcephaly, and growth failure. Postnatal features include severe developmental delay, congenital cataracts (in some), and marked UV sensitivity of the skin. Survival beyond 6 years of age is rare. COFS represents the severe end of the spectrum of disorders caused by mutations in nucleotide excision repair (NER) genes, with Cockayne syndrome and xeroderma pigmentosum being milder NER-related phenotypes (summary by Drury et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of cerebrooculofacioskeletal syndrome, see COFS1 (214150).
Spinocerebellar ataxia-34 is an autosomal dominant disorder characterized by slowly progressive cerebellar ataxia. The age at onset is usually during the young adult years, and most patients remain ambulatory until late in life. One family with SCA34 also had onset of erythema and hyperkeratosis in early childhood (Cadieux-Dion et al., 2014), whereas other families have additional neurologic signs, including ocular movement disturbances and pyramidal tract signs (Ozaki et al., 2015). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Familial erythroleukemia is a leukemic or preleukemic state in which red cell proliferation is the predominant feature. Hematologic characteristics include particularly ineffective and hyperplastic erythropoiesis with megaloblastic components accompanied by myeloblastic proliferation of varying degree (Park et al., 2002). Park et al. (2002) discussed the evolution of the definition of 'erythroleukemia,' which is considered by most to be a subtype of acute myelogenous leukemia (AML; 601626). Controversy about the precise definition of erythroleukemia revolves around the number or percentage of erythroblasts and myeloblasts found in the bone marrow and peripheral circulation. In the French-American-British (FAB) classification system (Bennett et al., 1985), it is known as AML-M6, whereas in the revised World Health Organization (WHO) classification system (Harris et al., 1999), it is known as 'AML, not otherwise categorized' (Zini and D'Onofrio, 2004).
Erythema palmare hereditarium is a benign condition that was first described by Lane (1929). Erythema usually presents at birth and remains stable throughout life. Histology shows dilated vessels in the entire dermis with inflammatory infiltrate. Capillaroscopy reveals an increased number of capillary loops running parallel to the surface (summary by Kluger and Guillot, 2010).
The disorders classically referred to as familial cylindromatosis, Brooke-Spiegler syndrome, and multiple familial trichoepithelioma were originally described as distinct clinical entities. Patients with BRSS develop multiple skin appendage tumors including cylindromas, trichoepitheliomas, and spiradenomas. Patients with familial cylindromatosis have only cylindromas, and those with MFT1 have only trichoepitheliomas. However, because these disorders show overlapping phenotypic features, and because different manifestations of each have been described within a single family, many consider these disorders to represent a phenotypic spectrum of a single disease entity (Guggenheim and Schnyder, 1961; Welch et al., 1968; Gerretsen et al., 1995; Lee et al., 2005; Bowen et al., 2005; Young et al., 2006; Saggar et al., 2008). Van Balkom and Hennekam (1994), who preferred the designation 'dermal eccrine cylindromatosis' for familial cylindromatosis, provided a review. 'Eccrine' referred to histologic evidence that the tumors may originate from the eccrine sweat glands. Blake and Toro (2009) provided a detailed review of the spectrum of disorders associated with CYLD mutations.
A severe bone dysplasia in which osteopathia striata is associated with cranial sclerosis, dysmorphic facies, cleft palate, deafness, heart defects, and vertebral anomalies with variability of expression. Neurological findings range from normal development to psychomotor retardation and hydrocephalus.
A decreased ability to move the femur at the hip joint associated with a decreased range of motion of the hip.
An ependymoma that arises from the central nervous system and occurs during childhood.
PDGFRB-associated chronic eosinophilic leukemia is a type of cancer of blood-forming cells. It is characterized by an elevated number of white blood cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRB-associated chronic eosinophilic leukemia. Some people with this condition have an increased number of other types of white blood cells, such as neutrophils or mast cells, in addition to eosinophils. People with this condition can have an enlarged spleen (splenomegaly) or enlarged liver (hepatomegaly). Some affected individuals develop skin rashes, likely as a result of an abnormal immune response due to the increased number of eosinophils.
Abnormally low level of eosinophils in the blood.
The presence of an adenoma of the pancreas with origin in a pancreatic B cell.
Lateral meningocele syndrome (LMS) is characterized by multiple lateral spinal meningoceles (protrusions of the arachnoid and dura through spinal foramina), distinctive facial features, joint hyperextensibility, hypotonia, and skeletal, cardiac, and urogenital anomalies. Neurologic sequelae of the meningoceles depend on size and location and can include neurogenic bladder, paresthesias, back pain, and/or paraparesis. Other neurologic findings can include Chiari I malformation, syringomyelia, and rarely, hydrocephalus. Additional findings of LMS include mixed or conductive hearing loss and cleft palate. Skeletal abnormalities may include scoliosis, vertebral fusion, scalloping of vertebrae, and wormian bones. Although developmental delay is common, cognition is often preserved. Feeding difficulties and gastroesophageal reflux disease (GERD) are common.
A widening or ballooning of the dural sac surrounding the spinal cord usually at the lumbosacral level.
Increased bone density of the skull base without significant changes in bony contour.
The presence of large polyhedral cells with eosinophilic granular cytoplasm and enlarged nuclei in the adrenal cortex.
This EEG variant is characterized by almost complete absence of alpha waves except, in some cases, for a few seconds after the eyes are closed and after hyperventilation (summary by Vogel and Motulsky, 1986).
A reduced ability to heal cutaneous wounds.
Absence or underdevelopment of the ear lobes.
A developmental defect consisting in the duplication of the first metatarsal bone.
A form of ectodermal dysplasia with hair, teeth and nail involvement. The disease has predominant characteristics of hypodontia, hypotrichosis, delayed hair growth and brittle nails. Additionally focal dermal hypoplasia, irregular hyperpigmentation, hypoplastic or absent nipples, amastia, hearing impairment, congenital hip dislocation and asthma have been associated. There have been no further descriptions in the literature since 1996.
Sharply demarcated, typically linear and approximately horizontal, indentations in the outer surface of the ear lobe.
A form of focal dystonia affecting the face and especially the jaw that is induced by the act of speaking. It is an involuntary contraction of the masticatory muscles, resulting in dysarthria or dysphagia.
GTP cyclohydrolase 1-deficient dopa-responsive dystonia (GTPCH1-deficient DRD) is characterized by childhood-onset dystonia and a dramatic and sustained response to low doses of oral administration of levodopa. This disorder typically presents with gait disturbance caused by foot dystonia, later development of parkinsonism, and diurnal fluctuation of symptoms (aggravation of symptoms toward the evening and alleviation of symptoms in the morning after sleep). Initial symptoms are often gait difficulties attributable to flexion-inversion (equinovarus posture) of the foot. Occasionally, initial symptoms are arm dystonia, postural tremor of the hand, or slowness of movements. Brisk deep-tendon reflexes in the legs, ankle clonus, and/or the striatal toe (dystonic extension of the big toe) are present in many affected individuals. In general, gradual progression to generalized dystonia is observed. Intellectual, cerebellar, sensory, and autonomic disturbances generally do not occur.
Episodes of choreoathetosis that can occur following triggers such as quick voluntary movements.
Dystonia-4, also known as whispering dysphonia, is an autosomal dominant neurologic disorder characterized by onset in the second to third decade of progressive laryngeal dysphonia followed by the involvement of other muscles, such as the neck or limbs. Some patients develop an ataxic gait (summary by Hersheson et al., 2013).
DYT1 early-onset isolated dystonia typically presents in childhood or adolescence and only on occasion in adulthood. Dystonic muscle contractions causing posturing or irregular tremor of a leg or arm are the most common presenting findings. Dystonia is usually first apparent with specific actions such as writing or walking. Over time, the contractions frequently (but not invariably) become evident with less specific actions and spread to other body regions. No other neurologic abnormalities are present. Disease severity varies considerably even within the same family. Isolated writer's cramp may be the only sign.
Kirner deformity, or dystelephalangy, is a rare malformation of the fifth finger that consists of radial bowing of the terminal phalanx, with the tip of the finger pointing toward the thenar eminence. The deformity is usually bilateral (summary by Temtamy and McKusick, 1978).
Dyslexia is a disorder manifested by difficulty learning to read despite conventional instruction, adequate intelligence, and sociocultural opportunity. It is among the most common neurodevelopmental disorders, with a prevalence of 5 to 12%. Although there is evidence for familial clustering and heritability, the disorder is considered a complex multifactorial trait (Schumacher et al., 2007). Genetic Heterogeneity of Susceptibility to Dyslexia Additional dyslexia susceptibility loci include DYX2 (600202) on chromosome 6p22, DYX3 (604254) on chromosome 2p16-p15, DYX5 (606896) on chromosome 3p12-q13, DYX6 (606616) on chromosome 18p11.2, DYX8 (608995) on chromosome 1p36-p34, and DYX9 (300509) on chromosome Xq27.3. See MAPPING for other possible dyslexia susceptibility loci, including DYX4 and DYX7.
Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.
Increased pigmentation of the skin with a netlike (reticular) pattern.
Partial dislocation of the ulna in the dorsal direction.
This syndrome has characteristics of multiple doughnut-shaped hyperostotic or osteosclerotic lesions of the calvaria. It has been observed in approximately 20 individuals. Clinical manifestations include the presence of cranial lumps, numerous pathologic fractures, elevated serum alkaline phosphatase levels, and dental caries. Transmission is autosomal dominant.
In general, the distal arthrogryposes are a group of disorders characterized by contractures mainly involving the distal parts of the limbs. The hands have a characteristic position with medially overlapping fingers, clenched fists, ulnar deviation of fingers, and camptodactyly, and the feet have deformities. Contractures at other joints are variable; there are no associated visceral anomalies, and intelligence is normal. Classically, DA was defined as being without overt neurologic or muscle disease (Lin et al., 1977 and Hall et al., 1982), although more recent evidence suggests that DA1A due to TPM2 mutations results from muscle dysfunction (Robinson et al., 2007; Mokbel et al., 2013; Davidson et al., 2013). The prototypic distal arthrogryposis is type 1 (DA1), which is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected. While the pattern of affected joints is consistent, the degree to which the joints are affected is highly variable, with equinovarus deformities ranging from mild to severe and hand involvement ranging from isolated hypoplasia of the distal interphalangeal crease of the fifth digit to severely clenched fists and ulnar deviation of the wrist. The various phenotypic forms of distal arthrogryposis are classified hierarchically according to the proportion of features they share with one another and are designated DA1 through DA10 (summary by Bamshad et al., 2009). Bamshad et al. (1996) revised the classification by Hall et al. (1982) of the common mendelian arthrogryposis syndromes. Krakowiak et al. (1997) provided a useful classification of the distal arthrogryposes. Genetic Heterogeneity of Distal Arthrogryposes Distal arthrogryposis type 1 includes DA1A, caused by mutation in the TPM2 gene, and DA1B (614335), caused by mutation in the MYBPC1 gene (160794) on chromosome 12q23. Other forms include DA2A (Freeman-Sheldon syndrome, 193700), caused by mutation in the MYH3 gene (160720) on chromosome 17p13; DA2B (Sheldon-Hall syndrome, 601680), caused by mutation in the MYH3 gene, the TNNT3 gene (600692) on chromosome 11p15, the TNNI2 gene (191043), also on 11p15, or TPM2 (190990) on chromosome 9p13; DA3 (Gordon syndrome, 114300) and DA5 (108145), caused by mutation in the PIEZO2 gene (613629) on chromosome 18p11; DA4 (609128); DA5D (615065), caused by mutation in the ECEL1 gene (605896) on chromosome 2q36; DA6 (108200); DA7 (158300), caused by mutation in the MYH8 gene (160741) on chromosome 17p13.1; DA8 (178110), caused by mutation in the MYH3 gene (160720) on chromosome 17p13; DA9 (121050), caused by mutation in the FBN2 gene (612570) on chromosome 5q23; and DA10 (187370), which maps to chromosome 2q. See 277720 for discussion of a possible autosomal recessive form of DA2A. See 208155 for a description of Illum syndrome, which includes 'whistling face,' central nervous system dysfunction, and calcium deposition in central nervous system and muscle. There are other forms of arthrogryposis multiplex congenita (AMC), including a lethal congenital form (see LCCS1, 253310).
Monogenic diabetes caused by inactivating mutation(s) in the gene HNF4A, encoding hepatocyte nuclear factor 4-alpha.
PPKS2 is characterized by linear hyperkeratosis of the palms, which is particularly evident in affected individuals who perform manual labor. Hyperkeratosis of the soles primarily involves pressure points, and diffuse background palmoplantar thickening may also be present. (Armstrong et al., 1999; Whittock et al., 1999). For a discussion of genetic heterogeneity of the striate form of palmoplantar keratoderma, see PPKS1 (148700).
A net-like pattern of increased pigmentation of the oral cavity.
Dermal ridge patterns are the result of the interaction of 2 embryologic processes: the formation and later regression of the volar pads between the eighth and twelfth week of gestation and dermal ridge differentiation at around the twelfth week of gestation. The size and shape of the volar pad at the time of ridge differentiation influences the ultimate ridge pattern: in general, if the pad is large, a whorl will be formed, whereas if the pad is small, a plain arch will be formed. A loop is an intermediate pattern. In Caucasians, the loop is the most common pattern, and the arch is a rare pattern comprising 4 to 5% of fingertip patterns in the population. Fingertip arches are more common in females than males (Reed et al, 2006).
Radiolucency (reflecting a reduction in the bony substance) around the apex (the tip of the dental root). [HPO:ibailleulforestier]
An acute condition characterized by sudden visual loss (usually discovered in the morning), optic disc edema at onset, optic disc-related visual field defects. Nonarteritic anterior ischemic optic neuropathy can be associated with flame hemorrhages on the swollen disc or nearby neuroretinal layer, and sometimes with nearby cotton-wool exudates.
This syndrome has characteristics of the association of congenital hearing loss and facial dysmorphism (facial asymmetry, a broad nasal root and small nasal alae). It has been described in two members (father and daughter) of one Jewish family. Temporal alopecia was also noted. Transmission appeared to be autosomal dominant.
DFNA1 is an autosomal dominant form of progressive hearing loss with onset in the first decade. Some patients may have mild thrombocytopenia and enlarged platelets, although most of these individuals do not have significant bleeding tendencies (summary by Neuhaus et al., 2017).
The presence of multiple pits (small, pinpoint-large indentations on the surface of the skin) located on the skin of sole of foot.
The syndrome has been described in a single Greek Cypriot family, over three generations. There have been no further descriptions in the literature since 1992. Affected individuals have a striking facial appearance (described as Mephistophelian) and variable skeletal deformities and neuromuscular abnormalities. The facial appearance consists of a thickened, ridged, triangular skin fold extending from the glabella to the anterior fontanelle, elevation of the medial portion of the eyebrows bilaterally, hypertelorism, low-set ears, posteriorly rotated ears and widow's peak. Musculoskeletal features may coexist and include congenital kyphoscoliosis, hip dislocation, congenital talipes equinovarus and arthrogryposis. Neurological and musculoskeletal defects are severe and incapacitating in some affected family members, while all have normal intelligence. The cause of this syndrome is not known.
Increased size of the ridge of tissue that extends along the midline of the scrotum.
A groove of the skin immediately in front of the ear.
Mutations in the CRYGC gene have been found to cause several types of cataract, which have been described as Coppock-like; embryonic, fetal, infantile nuclear; zonular pulverulent; and lamellar. Some patients also exhibit microcornea. Before it was known that mutations in the CRYGC gene cause several types of cataract, this entry was titled 'Cataract, Coppock-like,' with the symbol CCL.
Cryptophthalmos is a condition of eyelid malformation with an underlying malformed eye. Complete, incomplete, and symblepharon varieties exist. The skin in complete cryptophthalmos extends uninterrupted from the forehead to the cheek. In the incomplete form, there is medial eyelid fusion, but coincident intact lateral structures. The symblepharon variety presents with fusion of the upper eyelid skin to the superior aspect of the globe. The complete variety is the most common form (summary by Egier et al., 2005).
This syndrome describes a combination of malformations that include bilateral cryptomicrotia (recessed, hidden and small or absent ears), brachytelomesophalangy with short middle and distal phalanges of digits two through five, hypoplastic toenails and excess fingertip arch patterns. The syndrome has been reported in one family (mother and son). There have been no further descriptions in the literature since 1988.
Any abnormality of the cervical vertebral column.
Muscular rigidity (continuous contraction of muscles with constant resistance to passive movement).
Autosomal dominant craniometaphyseal dysplasia (designated AD-CMD in this review) is characterized by progressive diffuse hyperostosis of cranial bones evident clinically as wide nasal bridge, paranasal bossing, widely spaced eyes with an increase in bizygomatic width, and prominent mandible. Development of dentition may be delayed and teeth may fail to erupt as a result of hyperostosis and sclerosis of alveolar bone. Progressive thickening of craniofacial bones continues throughout life, often resulting in narrowing of the cranial foramina, including the foramen magnum. If untreated, compression of cranial nerves can lead to disabling conditions such as facial palsy, blindness, or deafness (conductive and/or sensorineural hearing loss). In individuals with typical uncomplicated AD-CMD life expectancy is normal; in those with severe AD-CMD life expectancy can be reduced as a result of compression of the foramen magnum.
Abnormal alignment, positioning, or spacing of the teeth, i.e., misaligned teeth.
Craniofacial-deafness-hand syndrome is characterized by distinctive facial features, profound hearing loss, and hand abnormalities.The distinctive facial features of people with craniofacial-deafness-hand syndrome result from a variety of developmental abnormalities involving the skull (cranium) and face. Affected individuals often have underdeveloped or absent nasal bones resulting in a small nose, thin nostrils, and a flattened mid-face with a flat nasal bridge. Individuals with this condition typically also have widely spaced eyes (ocular hypertelorism), narrowed openings of the eyes (narrowed palpebral fissures), a small upper jaw (hypoplastic maxilla), and a small mouth with pursed lips.People with this condition also have profound hearing loss that is caused by abnormalities in the inner ear (sensorineural deafness). Hearing loss in these individuals is present from birth.In affected individuals, a common abnormality of the muscles in the hand is a malformation in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). People with craniofacial-deafness-hand syndrome may also have permanently bent third, fourth, and fifth fingers (camptodactyly), which can limit finger movement and lead to joint deformities called contractures. Contractures in the wrist can further impair hand movements.
An extremely rare primary bone defect described only in a mother and her three daughters to date. The disease has characteristics of short stature, hip dislocation, minor vertebral and pelvic changes and microtia with hearing loss. There have been no further descriptions in the literature since 1981.
Tegafur is a chemotherapeutic agent and a member of the fluoropyrimidine group of substances. It is a prodrug of 5-fluorouracil and mainly used to treat solid tumors, such as colorectal, breast and aerodigestive cancers. Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) is the rate-limiting enzyme for fluoropyrimidine metabolism and is therefore responsible for the detoxification of these types of drugs. Patients who are homozygous for variants in DPYD that lead to a non-functional protein, such as *2A or *13, have a high risk of severe or fatal drug toxicities and may benefit from receiving an alternative chemotherapeutic drug. Patients heterozygous for these variants also have an increased risk for drug toxicities, and reduced dosing is recommended for these individuals. Guidelines regarding the use of pharmacogenomic tests in dosing for tegafur have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA452620).
A rare anomaly with characteristics of fixation of the scapula to the first rib, resulting in a cosmetic deformity with rounding of the shoulders and loss of the anterior clavicular contour. It has been described only once in several members of a single family from Canada. The abnormality resulted in a strong pectoral girdle with lack of mobility. Movements requiring rotation or retraction of the scapula were limited, but this does not normally interfere with daily activities.
Corticosteroid-binding globulin deficiency is a condition with subtle signs and symptoms, the most frequent being extreme tiredness (fatigue), especially after physical exertion. Many people with this condition have unusually low blood pressure (hypotension). Some affected individuals have a fatty liver or experience chronic pain, particularly in their muscles. These features vary among affected individuals, even those within the same family.Many people with corticosteroid-binding globulin deficiency have only one or two of these features; others have no signs and symptoms of the disorder and are only diagnosed after a relative is found to be affected.Some people with corticosteroid-binding globulin deficiency also have a condition called chronic fatigue syndrome. The features of chronic fatigue syndrome are prolonged fatigue that interferes with daily activities, as well as general symptoms, such as sore throat or headaches.
Underdevelopment of part or all of the male external reproductive organs (which include the penis, the scrotum and the urethra).
Increased susceptibility to coronavirus 229e, as manifested by recurrent episodes of coronavirus 229e.
Epithelial recurrent erosion dystrophy is characterized by frequent painful recurrent corneal erosions, with onset in the first decade of life and subsequent gradual decrease in frequency, with cessation in the third or fourth decade. Small gray anterior stromal flecks associated with larger focal gray-white disc-shaped, circular, or wreath-like lesions with central clarity, in the Bowman layer and immediately subjacent anterior stroma, varying from 0.2 to 1.5 mm in diameter, appear to be clinically diagnostic of ERED (Oliver et al., 2016).
Cornea plana is clinically characterized by reduced corneal curvature leading in most cases to hyperopia, hazy corneal limbus, and arcus lipoides at an early age. CNA1, an autosomal dominant form of the disorder, is mild (summary by Tahvanainen et al., 1996). Genetic Heterogeneity of Cornea Plana Also see CNA2 (217300), an autosomal recessive form of the disorder, which is severe and frequently associated with additional ocular manifestations.
A rare disorder of mineral absorption and transport characterised by hypocupraemia that manifests as failure to thrive, mild anaemia, repeated seizures, hypotonia and seborrhoeic skin. Spurring of the femur and tibia are also noted on radiographic imaging. Symptoms are reversible or improve with supplements of oral copper. There have been no further descriptions in the literature since 1982.
Childhood seizures associated with febrile episodes are relatively common and represent the majority of childhood seizures. A febrile convulsion is defined as a seizure event in infancy or childhood, usually occurring between 6 months and 6 years of age, associated with fever but without any evidence of intracranial infection or defined pathologic or traumatic cause (Nabbout et al., 2002). Although the majority of patients do not develop epilepsy, the risk of developing subsequent afebrile seizures is 5 to 7 times higher in those with a history of febrile seizures compared to the general population (Annegers et al., 1987; Hedera et al., 2006). The FEB1 locus maps to chromosome 8q13-q21. Genetic Heterogeneity of Familial Febrile Seizures FEB3A (604403) is caused by mutation in the SCN1A gene (182389) on chromosome 2q24; FEB3B (see 604403) is caused by mutation in the SCN9A gene (603415) on chromosome 2q24; FEB4 (604352) is caused by mutation in the ADGRV1 gene (602851) on chromosome 5q14; FEB8 (611277) is caused by mutation in the GABRG2 gene (137164) on chromosome 5q31; and FEB11 (614418) is caused by mutation in the CPA6 gene (609562) on chromosome 8q13. Several loci for familial febrile seizures have been identified: see FEB2 (602477) on chromosome 19p, FEB5 (609255) on chromosome 6q, FEB6 (609253) on chromosome 18p, FEB7 (611515) on chromosome 21q22, FEB9 (611634) on chromosome 3p24.2-p23, and FEB10 (612637) on chromosome 3q26. A phenotype termed 'generalized epilepsy with febrile seizures plus' (GEFS+; 604233) is a clinical subset of familial febrile convulsions in which affected individuals later develop afebrile seizures. GEFS+ is associated with mutations in several genes. Deprez et al. (2009) provided a review of the genetics of epilepsy syndromes starting in the first year of life, and included a diagnostic algorithm.
KCNQ3-related disorders include benign familial neonatal epilepsy (BFNE) and benign familial infantile epilepsy (BFIE), seizure disorders that occur in children who typically have normal psychomotor development. An additional KCNQ3-related disorder involves developmental disability. In BFNE seizures begin in an otherwise healthy infant between days two and eight of life and spontaneously disappear between the first and the sixth to 12th month of life. Seizures are generally brief, lasting one to two minutes. Seizure types include tonic or apneic episodes, focal clonic activity, and autonomic changes. Motor activity may be confined to one body part, migrate to other regions, or generalize. Infants are well between seizures and feed normally. In BFIE seizures start in the first year of life, beyond the neonatal period, and disappear after age one to two years. Seizures are generally brief, lasting two minutes; they appear as daily repeated clusters. Seizure type is usually focal, but can be also generalized, causing diffuse hypertonia with jerks of the limbs, head deviation, or motor arrest with unconsciousness and cyanosis. Infants are normal between seizures and psychomotor development is usually normal. In the KCNQ3-related developmental disability phenotype, individuals present with intellectual disability with or without seizures and/or cortical visual impairment. As little clinical information on these individuals is available, the clinical presentation of KCNQ3-related developmental disability remains to be defined.
Branchiootorenal (BOR) syndrome is a condition that disrupts the development of tissues in the neck and causes malformations of the ears and kidneys. The signs and symptoms of this condition vary widely, even among members of the same family. Branchiootic (BO) syndrome includes many of the same features as BOR syndrome, but affected individuals do not have kidney abnormalities. The two conditions are otherwise so similar that researchers often consider them together (BOR/BO syndrome or branchiootorenal spectrum disorders).""Branchio-"" refers to the second branchial arch, which is a structure in the developing embryo that gives rise to tissues in the front and side of the neck. In people with BOR/BO syndrome, abnormal development of the second branchial arch can result in the formation of masses in the neck called branchial cleft cysts. Some affected people have abnormal holes or pits called fistulae in the side of the neck just above the collarbone. Fistulae can form tunnels into the neck, exiting in the mouth near the tonsil. Branchial cleft cysts and fistulae can cause health problems if they become infected, so they are often removed surgically.""Oto-"" and ""-otic"" refer to the ear; most people with BOR/BO syndrome have hearing loss and other ear abnormalities. The hearing loss can be sensorineural, meaning it is caused by abnormalities in the inner ear; conductive, meaning it results from changes in the small bones in the middle ear; or mixed, meaning it is caused by a combination of inner ear and middle ear abnormalities. Some affected people have tiny holes in the skin or extra bits of tissue just in front of the ear. These are called preauricular pits and preauricular tags, respectively.""Renal"" refers to the kidneys; BOR syndrome (but not BO syndrome) causes abnormalities of kidney structure and function. These abnormalities range from mild to severe and can affect one or both kidneys. In some cases, end-stage renal disease (ESRD) develops later in life. This serious condition occurs when the kidneys become unable to filter fluids and waste products from the body effectively.
A malformation syndrome with the combination of bilateral coloboma of macula, horizontal pendular nystagmus, severe visual loss and brachydactyly type B. The hand and feet defects comprise shortening of the middle and terminal phalanges of the second to fifth digits, hypoplastic or absent nails, broad or bifid thumbs and halluces, syndactyly and flexion deformities of the joints of some digits. Inherited in a dominant manner.
PAX2-related disorder is an autosomal dominant disorder associated with renal and eye abnormalities. The disorder was originally referred to as renal coloboma syndrome and characterized by renal hypodysplasia and abnormalities of the optic nerve; with improved access to molecular testing, a wider range of phenotypes has been recognized in association with pathogenic variants in PAX2. Abnormal renal structure or function is noted in 92% of affected individuals and ophthalmologic abnormalities in 77% of affected individuals. Renal abnormalities can be clinically silent in rare individuals. In most individuals, clinically significant renal insufficiency / renal failure is reported. End-stage renal disease requiring renal transplant is not uncommon. Uric acid nephrolithiasis has been reported. Ophthalmologic abnormalities are typically described as optic nerve coloboma or dysplasia. Iris colobomas have not been reported in any individual with PAX2–related disorder. Ophthalmologic abnormalities may significantly impair vision in some individuals, while others have subtle changes only noted after detailed ophthalmologic examination. Additional clinical findings include high-frequency sensorineural hearing loss, soft skin, and ligamentous laxity. PAX2 pathogenic variants have been identified in multiple sporadic and familial cases of nonsyndromic renal disease including renal hypodysplasia and focal segmental glomerulosclerosis.
A congenital defect of the macula distinct from coloboma associated with optic fissure closure defects. Macular coloboma is characterized by a sharply defined, rather large defect in the central area of the fundus that is oval or round, and coarsely pigmented.
Cerebrooculofacioskeletal syndrome-4 is a severe autosomal recessive disorder characterized by growth retardation, dysmorphic facial features, arthrogryposis, and neurologic abnormalities. Cellular studies show a defect in both transcription-coupled and global genome nucleotide excision repair (TC-NER and GG-NER) (summary by Jaspers et al., 2007 and Kashiyama et al., 2013). For a discussion of genetic heterogeneity of cerebrooculofacioskeletal syndrome, see 214150.
SYNE1 deficiency comprises a phenotypic spectrum that ranges from autosomal recessive cerebellar ataxia at the mild end to arthrogryposis multiplex congenita (AMC) at the severe end. SYNE1-deficient cerebellar ataxia, the most commonly recognized manifestation of SYNE1 deficiency to date, is a slowly progressive disorder typically beginning in adulthood (age range 6-45 years). While some individuals have a pure cerebellar syndrome (i.e., cerebellar ataxia, dysarthria, dysmetria, abnormalities in ocular saccades and smooth pursuit), many also have upper motor neuron dysfunction (spasticity, hyperreflexia, Babinski sign) and/or lower motor neuron dysfunction (amyotrophy, reduced reflexes, fasciculations). Most patients develop features of the cerebellar cognitive and affective syndrome (i.e., significant deficits in attention, executive functioning, verbal working memory, and visuospatial/visuoconstructional skills). The two less common phenotypes are SYNE1-deficient childhood-onset multisystem disease (ataxia, upper and lower motor neuron dysfunction, muscle weakness and wasting, intellectual disability) and SYNE1-deficient arthrogryposis multiplex congenita (decreased fetal movements and severe neonatal hypotonia associated with multiple congenital joint contractures including clubfoot).
Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.Approximately 20 percent of people with severe congenital neutropenia develop certain cancerous conditions of the blood, particularly myelodysplastic syndrome or leukemia during adolescence.Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.
Nephrotic syndrome, a malfunction of the glomerular filter, is characterized clinically by proteinuria, edema, and end-stage renal disease (ESRD). Renal histopathology may show diffuse mesangial sclerosis (DMS) or focal segmental glomerulosclerosis (FSGS) (Hinkes et al., 2006). Most patients with NPHS3 show diffuse mesangial sclerosis on renal biopsy, which is a pathologic entity characterized by mesangial matrix expansion with no mesangial hypercellularity, hypertrophy of the podocytes, vacuolized podocytes, thickened basement membranes, and diminished patency of the capillary lumen (Gbadegesin et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Neutral lipid storage disease with myopathy is an autosomal recessive muscle disorder characterized by adult onset of slowly progressive proximal muscle weakness affecting the upper and lower limbs and associated with increased serum creatine kinase; distal muscle weakness may also occur. About half of patients develop cardiomyopathy later in the disease course. Other variable features include diabetes mellitus, hepatic steatosis, hypertriglyceridemia, and possibly sensorineural hearing loss. Leukocytes and muscle cells show cytoplasmic accumulation of triglycerides (summary by Reilich et al., 2011). Neutral lipid storage disease with myopathy belongs to a group of disorders termed neutral lipid storage disorders (NLSDs). These disorders are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Chanarin-Dorfman syndrome (CDS; 275630) is defined as NLSD with ichthyosis (NLSDI). Patients with NLSDM present with myopathy but without ichthyosis (summary by Fischer et al., 2007).
OPA5 is an autosomal dominant form of nonsyndromic optic atrophy, manifest as slowly progressive visual loss with variable onset from the first to third decades. Additional ocular abnormalities may include central scotoma and color vision defects. The pathogenesis is related to defective mitochondrial fission (summary by Gerber et al., 2017). For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
Congenital deafness with labyrinthine aplasia, microtia, and microdontia (LAMM syndrome) is characterized by: profound bilateral congenital sensorineural deafness associated with inner ear anomalies (most often bilateral complete labyrinthine aplasia); microtia (type I) that is typically bilateral (although unilateral microtia and normal external ears are observed on occasion); and microdontia (small teeth). Individuals with LAMM syndrome commonly have motor delays during infancy presumably due to impaired balance from inner ear (vestibular) abnormalities. Growth, physical development, and cognition are normal.
Osteogenesis imperfecta is a connective tissue disorder characterized by bone fragility and low bone mass. OI type VII is an autosomal recessive form of severe or lethal OI (summary by Barnes et al., 2006).
The presence of bone fractures in the prenatal period that are diagnosed at birth or before.
Infections of the skin that happen multiple times.
Glycosylphosphatidylinositol is a glycolipid that anchors more than 150 proteins to the cell surface, and these proteins, termed GPI-anchored proteins (GPI-APs), have various important roles. Reduced surface levels of GPI-APs or abnormal GPI-AP structure can cause various symptoms, mainly including intellectual disability, and sometimes other congenital malformations, seizures, or dysmorphic facial features (summary by Makrythanasis et al., 2016). Genetic Heterogeneity of Glycosylphosphatidylinositol Biosynthesis Defects Also see GPIBD2 (239300), caused by mutation in the PIGV gene (610274); GPIBD3 (614080), caused by mutation in the PIGN gene (606097); GPIBD4 (300868), caused by mutation in the PIGA gene (311770); GPIBD5 (280000), caused by mutation in the PIGL gene (605947); GPIBD6 (614749), caused by mutation in the PIGO gene (614730); GPIBD7 (615398), caused by mutation in the PIGT gene (610272); GPIBD8 (614207), caused by mutation in the PGAP2 gene (615187); GPIBD9 (615802), caused by mutation in the PGAP1 gene (611655); GPIBD10 (615716), caused by mutation in the PGAP3 gene (611801); GPIBD11 (616025), caused by mutation in the PIGW gene (610275); GPIBD12 (616809), caused by mutation in the PIGY gene (610662); GPIBD13 (616917), caused by mutation in the PIGG gene (616918); GPIBD14 (617599), caused by mutation in the PIGP gene (605938); GPIBD15 (617810), caused by mutation in the GPAA1 gene (603048); GPIBD16 (617816), caused by mutation in the PIGC gene (601730); GPIBD17 (618010), caused by mutation in the PIGH gene (600154); and GPIBD18 (618143), caused by mutation in the PIGS gene (610271).
Anterior segment dysgeneses are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes, including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Some patients with ASGD2 have been reported with a congenital primary aphakia subtype. Congenital primary aphakia is a rare developmental disorder characterized by absence of the lens, the development of which is normally induced during the fourth to fifth week of human embryogenesis. This original failure leads, in turn, to complete aplasia of the anterior segment of the eye, which is the diagnostic histologic criterion for CPAK. In contrast, in secondary aphakia, lens induction occurs and the lens vesicle develops to some degree, but is progressively resorbed perinatally, resulting in less severe ocular defects (summary by Valleix et al., 2006).
A congenital anomaly in which a part or the whole of the cornea acquires the characteristics of sclera, resulting in clouding of the cornea.
Cases of the disease in question occur without a previous family history, i.e., as isolated cases without being transmitted from a parent and without other siblings being affected.
A congenital malformation of the outflow tract of the heart. Conotruncal defects are thought to result from a disturbance of the outflow tract of the embryonic heart, and comprise truncus arteriosus, tetralogy of Fallot, interrupted aortic arch, transposition of the great arteries, and double outlet right ventricle.
Absence of concavity or convexity of the face when viewed in profile.
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle. [DDD:jclayton-smith, pmid:19125436]
An abnormal configuration of the lower lip such that it is turned outward i.e., everted, with the Inner aspect of the lower lip vermilion (normally opposing the teeth) being visible in a frontal view.
Spastic paraplegia type 31 is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia) caused by degeneration of nerve cells (neurons) that trigger muscle movement. Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only the lower limbs, while the complicated types also involve the upper limbs and other areas of the body, including the brain. Spastic paraplegia type 31 is usually a pure hereditary spastic paraplegia, although a few complicated cases have been reported.The first signs and symptoms of spastic paraplegia type 31 usually appear before age 20 or after age 30. An early feature is difficulty walking due to spasticity and weakness, which typically affect both legs equally. People with spastic paraplegia type 31 can also experience progressive muscle wasting (amyotrophy) in the lower limbs, exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, reduced bladder control, and high-arched feet (pes cavus). As the condition progresses, some individuals require walking support.
Spinocerebellar ataxia type 28 (SCA28) is characterized by young-adult onset, very slowly progressive gait and limb ataxia resulting in coordination and balance problems, dysarthria, ptosis, nystagmus, and ophthalmoparesis. In most individuals, SCA28 presents as a loss of coordination of lower limbs (unsteadiness, gait ataxia). Less frequently, ptosis/ophthalmoplegia, dysarthria, or upper-limb incoordination may occur as the initial finding. The course of the disease is slowly progressive without impairment of functional autonomy even decades after onset.
Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder characterized by the presence of hypophosphatemia secondary to renal phosphate wasting, radiographic and/or histologic evidence of rickets, limb deformities, muscle weakness, and bone pain. HHRH is distinct from other forms of hypophosphatemic rickets in that affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption (summary by Bergwitz et al., 2006).
An autosomal recessive disorder caused by mutations in the TRIOBP gene, encoding TRIO and F-actin-binding protein. The condition is characterized by severe to profound sensorineural hearing loss.
Platelet-type bleeding disorder-8 is an autosomal recessive condition characterized by mild to moderate mucocutaneous bleeding and excessive bleeding after surgery or trauma. The defect is due to the inability of ADP to induce platelet aggregation (review by Cattaneo, 2011).
Familial erythrocytosis is an inherited condition characterized by an increased number of red blood cells (erythrocytes). The primary function of these cells is to carry oxygen from the lungs to tissues and organs throughout the body. Signs and symptoms of familial erythrocytosis can include headaches, dizziness, nosebleeds, and shortness of breath. The excess red blood cells also increase the risk of developing abnormal blood clots that can block the flow of blood through arteries and veins. If these clots restrict blood flow to essential organs and tissues (particularly the heart, lungs, or brain), they can cause life-threatening complications such as a heart attack or stroke. However, many people with familial erythrocytosis experience only mild signs and symptoms or never have any problems related to their extra red blood cells.
The presence of an increased mass of red blood cells in the circulation.
Syndactyly type I (185900) is an autosomal dominant limb malformation characterized in its classical form by complete or partial webbing between the third and fourth fingers and/or the second and third toes. Zygodactyly is a subtype of type I syndactyly in which webbing of second and third toes occurs without hand involvement (summary by Malik et al., 2005).
Monogenic diabetes caused by inactivating mutation(s) in the gene NEUROD1, encoding neurogenic differentiation 1. In addition to diabetes, this condition may be associated with neurogenic anomalies. Homozygous NEUROD1 mutations result in permanent neonatal diabetes.
Increase in size of the cisterna magna, one of three principal openings in the subarachnoid space between the arachnoid and pia mater, located between the cerebellum and the dorsal surface of the medulla oblongata.
Immunodeficiency-41 is an autosomal recessive complex disorder of immune dysregulation. Affected individuals present in infancy with recurrent viral, fungal, and bacterial infections, lymphadenopathy, and variable autoimmune features, such as autoimmune enteropathy and eczematous skin lesions. Immunologic studies show a defect in T-cell regulation (summary by Goudy et al., 2013).
Horizontal nystagmus made apparent by looking to the right or to the left.
ALS2-related disorders involve retrograde degeneration of the upper motor neurons of the pyramidal tracts and comprise a clinical continuum from infantile ascending hereditary spastic paraplegia (IAHSP), to juvenile forms without lower motor neuron involvement (juvenile primary lateral sclerosis [JPLS]), to forms with lower motor neuron involvement (autosomal recessive juvenile amyotrophic lateral sclerosis [JALS]). IAHSP is characterized by onset of spasticity with increased reflexes and sustained clonus of the lower limbs within the first two years of life, progressive weakness and spasticity of the upper limbs by age seven to eight years, and wheelchair dependence in the second decade with progression toward severe spastic tetraparesis and a pseudobulbar syndrome. JPLS is characterized by onset and loss of ability to walk during the second year of life, progressive signs of upper motor neuron disease, wheelchair dependence by adolescence, and later loss of motor speech production. JALS is characterized by onset during childhood (mean age of onset 6.5 years), spasticity of facial muscles, uncontrolled laughter, spastic dysarthria, spastic gait, moderate muscle atrophy (variably present), bladder dysfunction, and sensory disturbances; some individuals are bedridden by age 12 to 50 years.
Spasticity of one or more muscles innervated by the facial nerve.
Heterotaxy ('heter' meaning 'other' and 'taxy' meaning 'arrangement'), or situs ambiguus, is a developmental condition characterized by randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another (Srivastava, 1997). Heterotaxy is a clinically and genetically heterogeneous disorder. For a discussion of the genetic heterogeneity of visceral heterotaxy, see HTX1 (306955).
Stature (adult height) is an example of a complex genetic trait involving multiple genetic loci. Although complex traits are often difficult to study by linkage analysis, Hirschhorn et al. (2001) suggested that stature is a suitable complex trait for study because of the high heritability and the relatively limited contribution of environmental factors. Thus, linkage analysis has been used to identify quantitative trait loci for stature (STQTL) including STQTL1 on chromosome 6q24, STQTL2 (606256) on chromosome 7q31-q36, STQTL3 (606257) on chromosome 12p11-q14, STQTL4 (606258) on chromosome 13q32-q33, STQTL5 (608982) on chromosome 3p26, STQTL6 (300591) on chromosome Xq24, STQTL7 (609822) on chromosome 1p21, STQTL8 (610114) on chromosome 9q22, STQTL9 (611547) on chromosome 12q14.3, STQTL10 (612221) on chromosome 3q23, STQTL11 (612223) on chromosome 7q21-q22, STQTL12 (612224) on chromosome 4q28-q32, STQTL13 (612226) on chromosome 4p13.3, STQTL14 (612228) on chromosome 20q11.22, STQTL15 (612578) on chromosome 8q21.13, STQTL16 (612579) on chromosome 15q22.31, STQTL17 (612737) on chromosome 7p15, STQTL18 (612892) on chromosome 6p22.1, STQTL19 (612893) on chromosome 6p21.31, STQTL20 (612894) on chromosome 13q14.3, STQTL21 (613440) on chromosome 2q37.1, STQTL22 (613547) on chromosome 16q24, STQTL23 (613548) on chromosome 1p32, and STQTL24 (613549) on chromosome 2p16. See also X-linked short stature (300582) associated with mutations in the SHOX gene (312865).
Frontal hairline with bilateral arcs to a low point in the midline of the forehead.
Increased density/number and/or increased diameter of eyebrow hairs.
Phelan-McDermid syndrome is characterized by neonatal hypotonia, absent to severely delayed speech, developmental delay, and minor dysmorphic facial features. Most affected individuals have moderate to profound intellectual disability. Other features include large fleshy hands, dysplastic toenails, and decreased perspiration that results in a tendency to overheat. Normal stature and normal head size distinguishes Phelan-McDermid syndrome from other autosomal chromosome disorders. Behavior characteristics include mouthing or chewing non-food items, decreased perception of pain, and autism spectrum disorder or autistic-like affect and behavior.
Heterotaxy syndrome is a condition in which the internal organs are abnormally arranged in the chest and abdomen. The term ""heterotaxy"" is from the Greek words ""heteros,"" meaning ""other than,"" and ""taxis,"" meaning ""arrangement."" Individuals with this condition have complex birth defects affecting the heart, lungs, liver, spleen, intestines, and other organs.In the normal body, most of the organs in the chest and abdomen have a particular location on the right or left side. For example, the heart, spleen, and pancreas are on the left side of the body, and most of the liver is on the right. This normal arrangement of the organs is known as ""situs solitus."" Rarely, the orientation of the internal organs is completely flipped from right to left, a situation known as ""situs inversus."" This mirror-image orientation usually does not cause any health problems, unless it occurs as part of a syndrome affecting other parts of the body. Heterotaxy syndrome is an arrangement of internal organs somewhere between situs solitus and situs inversus; this condition is also known as ""situs ambiguus."" Unlike situs inversus, the abnormal arrangement of organs in heterotaxy syndrome often causes serious health problems.Heterotaxy syndrome can alter the structure of the heart, including the attachment of the large blood vessels that carry blood to and from the rest of the body. It can also affect the structure of the lungs, such as the number of lobes in each lung and the length of the tubes (called bronchi) that lead from the windpipe to the lungs. In the abdomen, the condition can cause a person to have no spleen (asplenia) or multiple small, poorly functioning spleens (polysplenia). The liver may lie across the middle of the body instead of being in its normal position to the right of the stomach. Some affected individuals also have intestinal malrotation, which is an abnormal twisting of the intestines that occurs in the early stages of development before birth.Depending on the organs involved, signs and symptoms of heterotaxy syndrome can include a bluish appearance of the skin or lips (cyanosis, which is due to a shortage of oxygen), breathing difficulties, an increased risk of infections, and problems with digesting food. The most serious complications are generally caused by critical congenital heart disease, a group of complex heart defects that are present from birth. Biliary atresia, a problem with the bile ducts in the liver, can also cause severe health problems in infancy.The severity of heterotaxy syndrome varies depending on the specific abnormalities involved. Some affected individuals have only mild health problems related to the condition. At the other end of the spectrum, heterotaxy syndrome can be life-threatening in infancy or childhood, even with treatment.
The term 'atrioventricular septal defect' (AVSD) covers a spectrum of congenital heart malformations characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. In ostium primum atrial septal defect (ASD) there are separate atrioventricular valvar orifices despite a common junction, whereas in complete AVSD the valve itself is also shared (summary by Craig, 2006). AVSD, also designated endocardial cushion defect or atrioventricular canal defect (AVCD), is known to occur in either a nonsyndromic (isolated) form or, more commonly, as part of a malformation syndrome. The 2 syndromes most frequently associated with AVSD are Down syndrome (190685), in which AVSD is the most frequent congenital heart defect, and Ivemark syndrome (208530) (summary by Carmi et al., 1992). Genetic Heterogeneity of Isolated Atrioventricular Septal Defect An AVSD susceptibility locus (AVSD1) maps to chromosome 1p31-p21; AVSD2 (606217) is caused by mutation in the CRELD1 gene (607170) on chromosome 3p25; AVSD3 (600309) is caused by mutation in the GJA1 gene (121014) on chromosome 6q22; AVSD4 (614430) is caused by mutation in the GATA4 gene (600576) on chromosome 8p23.1; and AVSD5 (614474) is caused by mutation in the GATA6 gene (601656) on chromosome 18q11. Somatic mutations in the HAND1 gene (602406) have been identified in tissue samples from patients with AVSDs.
Onset of disease manifestations in adulthood, defined here as at the age of 16 years or later.
KAT6B-related disorders include genitopatellar syndrome (GPS) and Say-Barber-Biesecker variant of Ohdo syndrome (Ohdo syndrome, SBBYS variant, or SBBYSS [Say-Barber-Biesecker-Young-Simpson syndrome]). Both phenotypes are characterized by significant global developmental delay / intellectual disability, hypotonia, genital abnormalities in males (cryptorchidism), and patellar hypoplasia/agenesis. Congenital heart defects, dental anomalies, hearing loss, and thyroid anomalies are common to both phenotypes. Also observed in GPS are flexion contractures of the hips and knees, clubfoot, agenesis of the corpus callosum with microcephaly, and hydronephrosis and/or multiple renal cysts. In SBBYS lower-extremity joint stiffness, long thumbs / great toes, immobile mask-like face, blepharophimosis/ptosis, and lacrimal duct anomalies are observed.
Neuroferritinopathy typically presents with progressive adult-onset chorea or dystonia affecting one or two limbs, and subtle cognitive deficits. The movement disorder affects additional limbs within five to ten years and becomes more generalized within 20 years. When present, asymmetry remains throughout the course of the disorder. The majority of individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity and orolingual dyskinesia are common. Cognitive deficits and behavioral issues become major problems with time.
Increased dimensions of the Virchow-Robin spaces (also known as perivascular spaces), which surround the walls of vessels as they course from the subarachnoid space through the brain parenchyma. Perivascular spaces are commonly microscopic, and not visible on conventional neuroimaging. This term refers to an increase of size of these spaces such that they are visible on neuroimaging (usually magnetic resonance imaging). The dilatations are regular cavities that always contain a patent artery. [ORCID:0000-0001-5208-3432, pmid:17620468, pmid:23867200]
Iris coloboma, ptosis, hypertelorism, broad nasal bridge, short stature, and mental retardation are the main elements of this syndrome.
Increased side-to-side width of the neck.
Multinodular goiter is a common disorder characterized by nodular enlargement of the thyroid gland (summary by Takahashi et al., 2001). For additional phenotypic information and a discussion of genetic heterogeneity of multinodular goiter, see MNG1 (138800).
Mechanical percussion (i.e., striking a muscle with a reflex hammer) leads to spreading waves of muscle contractions that begin proximally and spread laterally across the muscle.
Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hereditary hemochromatosis is also called an iron overload disorder.Early symptoms of hereditary hemochromatosis may include extreme tiredness (fatigue), joint pain, abdominal pain, weight loss, and loss of sex drive. As the condition worsens, affected individuals may develop arthritis, liver disease (cirrhosis) or liver cancer, diabetes, heart abnormalities, or skin discoloration. The appearance and severity of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.There are four types of hereditary hemochromatosis, which are classified depending on the age of onset and other factors such as genetic cause and mode of inheritance.Type 1, the most common form of the disorder, and type 4 (also called ferroportin disease) begin in adulthood. Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause.Type 2 hemochromatosis is known as a juvenile-onset disorder because symptoms often begin in childhood. By age 20, iron accumulation causes decreased or absent secretion of sex hormones. Affected females usually begin menstruation normally but menses stop after a few years. Males may experience delayed puberty or symptoms related to a shortage of sex hormones. If type 2 hemochromatosis is untreated, potentially fatal heart disease becomes evident by age 30.The onset of type 3 hemochromatosis is usually intermediate between types 1 and 2 with symptoms generally beginning before age 30.
A form of congenital disorders of N-linked glycosylation characterised by generalised hypotonia, craniofacial dysmorphism (prominent occiput, short palpebral fissures, long eyelashes, broad nose, high arched palate, retrognathia), hypoplastic genitalia, seizures, feeding difficulties, hypoventilation, severe hypogammaglobulinaemia with generalised oedema and increased resistance to particular viral infections (particularly to enveloped viruses). The disease is caused by loss-of-function mutations in the gene MOGS (2p13.1).
Increased convexity of the occiput (posterior part of the skull).
Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
IDDAS is a neurodevelopmental disorder characterized by varying degrees of intellectual disability, autism spectrum disorder, and language deficits (Deriziotis et al., 2014; den Hoed et al., 2018).
Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset of ataxia between age three and 30 years after initial normal development, axonal sensorimotor neuropathy, oculomotor apraxia, cerebellar atrophy, and elevated serum concentration of alpha-fetoprotein (AFP).
Atrophy affecting the pons and the cerebellum.
A decrease in the ability to perceive vibration in the distal portions of the limbs.
Syndrome with characteristics of a combination of distal limb abnormalities (syndactyly of all fingers and toes, preaxial polydactyly in the feet and/or hands) and upper sternum malformations. It has been described in 22 patients from a six-generation Turkish family. It is transmitted as an autosomal dominant trait and the causative gene is located at 7q36.
Characterised by metaphyseal undermodelling with broadening of the long bones and femora with an 'Erlenmeyer flask' appearance, expansion and bowing of the radii with severe varus deformity and flat exostoses of the long bones at the metadiaphyseal junctions. It has been described in four German families originating from the same town in Bohemia and in a 7-year-old Japanese girl. Transmission is autosomal dominant.
PINK1 type of young-onset Parkinson disease is characterized by early onset (mean age 33 years) of tremor, bradykinesia, and rigidity that are often indistinguishable from other causes of Parkinson disease. Lower-limb dystonia may be a presenting sign. Postural instability, hyperreflexia, abnormal behavior, and psychiatric manifestations have been described. The disease is usually slowly progressive. Individuals have a marked and sustained response to oral administration of levodopa (L-dopa), frequently associated with L-dopa-induced fluctuations and dyskinesias.
An extremely rare autosomal recessive glycine metabolism disorder characterised clinically in the single reported case to date by muscle fatigue and a fish-like odour.
An abnormality of Krebs cycle metabolism that is characterized by a decreased rate of fumarate hydratase activity.
Spondylo-ocular syndrome is a very rare association of spinal and ocular manifestations that is characterized by dense cataracts, and retinal detachment along with generalized osteoporosis and platyspondyly. Mild craniofacial dysphormism has been reported including short neck, large head and prominent eyebrows.
Presence of abnormal vacuoles (membrane-bound organelles) in the sarcolemma. On histological staining with hematoxylin and eosin, rimmed vacuoles are popcorn-like clear vacuoles with a densely blue rim. The vacuoles are often associated with cytoplasmic and occasionally intranuclear eosinophilic inclusions.
Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2). Often citrin deficiency is characterized by strong preference for protein-rich and/or lipid-rich foods and aversion to carbohydrate-rich foods. NICCD. Children younger than age one year have a history of low birth weight with growth restriction and transient intrahepatic cholestasis, hepatomegaly, diffuse fatty liver, and parenchymal cellular infiltration associated with hepatic fibrosis, variable liver dysfunction, hypoproteinemia, decreased coagulation factors, hemolytic anemia, and/or hypoglycemia. NICCD is generally not severe and symptoms often resolve by age one year with appropriate treatment, although liver transplantation has been required in rare instances. FTTDCD. Beyond age one year, many children with citrin deficiency develop a protein-rich and/or lipid-rich food preference and aversion to carbohydrate-rich foods. Clinical abnormalities may include growth restriction, hypoglycemia, pancreatitis, severe fatigue, anorexia, and impaired quality of life. Laboratory changes are dyslipidemia, increased lactate-to-pyruvate ratio, higher levels of urinary oxidative stress markers, and considerable deviation in tricarboxylic acid (TCA) cycle metabolites. One or more decades later, some individuals with NICCD or FTTDCD develop CTLN2. CTLN2. Presentation is sudden and usually between ages 20 and 50 years. Manifestations are recurrent hyperammonemia with neuropsychiatric symptoms including nocturnal delirium, aggression, irritability, hyperactivity, delusions, disorientation, restlessness, drowsiness, loss of memory, flapping tremor, convulsive seizures, and coma. Symptoms are often provoked by alcohol and sugar intake, medication, and/or surgery. Affected individuals may or may not have a prior history of NICCD or FTTDCD.
An abnormal reduction in the amplitude of the miniature endplate potentials, i.e. the postsynaptic response to transmitter released from an individual vesicle at the neuromuscular junction.
Atopic dermatitis (also known as atopic eczema) is a disorder characterized by inflammation of the skin (dermatitis). The condition usually begins in early infancy, and it often disappears before adolescence. However, in some affected individuals the condition continues into adulthood; in others, it does not begin until adulthood. Hallmarks of atopic dermatitis include dry, itchy skin and red rashes that come and go. The rashes can occur on any part of the body, although the pattern tends to be different at different ages. In affected infants, the rashes commonly occur on the face, scalp, hands, and feet. In children, the rashes are usually found in the bend of the elbows and knees and on the front of the neck. In adolescents and adults, the rashes typically occur on the wrists, ankles, and eyelids in addition to the bend of the elbows and knees. Scratching the itchy skin can lead to oozing and crusting of the rashes and thickening and hardening (lichenification) of the skin. The itchiness can be so severe as to disturb sleep and impair a person's quality of life.The word ""atopic"" indicates an association with allergies. While atopic dermatitis is not always due to an allergic reaction, it is commonly associated with other allergic disorders: up to 60 percent of people with atopic dermatitis develop asthma or hay fever (allergic rhinitis) later in life, and up to 30 percent have food allergies. Atopic dermatitis is often the beginning of a series of allergic disorders, referred to as the ""atopic march."" Development of these disorders typically follows a pattern, beginning with atopic dermatitis, followed by food allergies, then hay fever, and finally asthma. However, not all individuals with atopic dermatitis will progress through the atopic march, and not all individuals with one allergic disease will develop others.Individuals with atopic dermatitis have an increased risk of developing other conditions related to inflammation, such as inflammatory bowel disease, rheumatoid arthritis, and hair loss caused by a malfunctioning immune reaction (alopecia areata). They also have an increased risk of having a behavioral or psychiatric disorder, such as attention deficit hyperactivity disorder (ADHD) or depression.In a particular subset of individuals with atopic dermatitis, the immune system is unable to protect the body from foreign invaders such as bacteria and fungi (which is known as immunodeficiency). These individuals are prone to recurrent infections. Most also have other allergic disorders, such as asthma, hay fever, and food allergies.Atopic dermatitis can also be a feature of separate disorders that have a number of signs and symptoms, which can include skin abnormalities and immunodeficiency. Some such disorders are Netherton syndrome; immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome; and severe dermatitis, multiple allergies, metabolic wasting (SAM) syndrome.
Isolated congenital onychodysplasia, here referred to as nonsyndromic congenital nail disorder-7 (NDNC7), is characterized by longitudinal streaks, thinning, and impaired formation of the nail plates leading to increased vulnerability of the free nail margins. The most characteristic finding is a conspicuous reddish dome-shaped prominence of the proximal nail plate from which the longitudinal ridges originate, but this is present in only about half of patients. In most cases, all fingernails and toenails are involved, with some accentuation of the changes in the thumb nails and great toe nails (summary by Hamm et al., 2000 and Krebsova et al., 2000). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
PRRT2-associated paroxysmal movement disorders (PRRT2-PxMD) include paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC), and hemiplegic migraine (HM). In addition, PRRT2 pathogenic variants have been identified in other childhood-onset movement disorders and different types of seizures, suggesting that the understanding of the spectrum of PRRT2-PxMD is still evolving. The paroxysmal attacks in PKD are characterized by dystonia, choreoathetosis, and less commonly ballismus. The seizures of BFIE are usually focal with or without generalization. Thirty percent of PRRT2-associated PKD is associated with BFIE and is referred to as PKD/IC.
A locus on chromosome 9q12-q22 has been found for multiple types of cataract in 1 family. These include cortical, pulverulent, nuclear, and posterior subcapsular cataracts. The preferred title/symbol for this entry was formerly 'Cataract, Autosomal Recessive, Early-Onset, Pulverulent; CAAR.'
Distal spinal muscular atrophy-2 is an autosomal recessive neuromuscular disorder characterized by onset of distal muscle weakness and wasting affecting the lower and upper limbs in the first decade; there is no sensory involvement (summary by Li et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of DSMA, see HMN1 (182960).
This syndrome has characteristics of woolly hair, palmoplantar keratoderma and dilated cardiomyopathy principally affecting the left ventricle. Only a few cases have been reported, all involving patients from Ecuador, India or Turkey. The woolly hair is present at birth and the palmoplantar keratoderma appears during the first year of life. The cardiac anomaly presents during childhood and is marked by dilation of the left ventricle accompanied by alterations in muscle contractility. The syndrome is transmitted as an autosomal recessive trait and is caused by mutations in the DSP gene (6p24) encoding desmoplakin, a protein involved in cell adhesion. The syndrome is similar to Naxos disease.
Late-onset retinal degeneration (LORD) is an autosomal dominant disorder characterized by onset in the fifth to sixth decade with night blindness and punctate yellow-white deposits in the retinal fundus, progressing to severe central and peripheral degeneration, with choroidal neovascularization and chorioretinal atrophy (Hayward et al., 2003).
Proximal myopathy and ophthalmoplegia is a relatively mild muscle disorder characterized by childhood onset of symptoms. The disorder is either slowly progressive or nonprogressive, and affected individuals retain ambulation, although there is variable severity. MYPOP can show both autosomal dominant and autosomal recessive inheritance; the phenotype is similar in both forms (summary by Lossos et al., 2005 and Tajsharghi et al., 2014).
Familial hyperaldosteronism type II is an autosomal dominant disorder characterized by hypertension due to increased aldosterone, often with hypokalemia. Patients usually present before age 20 years, although some may present in infancy. The disorder shows incomplete penetrance and variable expressivity; some patients may have normal blood pressure but have an increased aldosterone:renin ratio (ARR) on laboratory testing. Spironolactone is an effective treatment (summary by Scholl et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of familial hyperaldosteronism, see HALD1 (103900).
A multisystem malformation syndrome that has been reported in about 10 patients. The clinical features include bilateral anophthalmia, abnormal nares, central nervous system anomalies, and neurodevelopmental delay. Additional features include brachycephaly and other facial anomalies. Non-facial anomalies have also been reported: postaxial polydactyly, genital hypoplasia. All cases reported so far have been sporadic, suggesting that the syndrome may be due to a new dominant mutation.
Distance between the philtral ridges, measured just above the vermilion border, more than 2 standard deviations above the mean, or alternatively, an apparently increased distance between the ridges of the philtrum.
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies. On the basis of electrophysiologic criteria, CMT is divided into 2 major types: type 1, the demyelinating form, characterized by a motor median nerve conduction velocity less than 38 m/s (see CMT1B; 118200); and type 2, the axonal form, with a normal or slightly reduced nerve conduction velocity. For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A1 (118210). Autosomal recessive forms of CMT are less frequent than the autosomal dominant or X-linked forms. One form of autosomal recessive axonal CMT (CMT2B1; 605588) is caused by mutation in the LMNA gene (150330) on chromosome 1q21.2-q21.3.
Charcot-Marie-Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies. On the basis of electrophysiologic criteria, CMT is divided into 2 major types: type 1, the demyelinating form, characterized by a motor median nerve conduction velocity less than 38 m/s (see CMT1B; 118200); and type 2, the axonal form, with a normal or slightly reduced nerve conduction velocity. For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A1 (118210).
Hereditary gingival fibromatosis is a benign disorder manifested by a slowly progressive enlargement of the oral gingival tissues (summary by Xiao et al., 2001). For general phenotypic information and a discussion of genetic heterogeneity of hereditary gingival fibromatosis, see GINGF (135300).
Alzheimer disease (AD) is a neurodegenerative disorder characterized by subtle onset of memory loss followed by a slowly progressive dementia. The great majority of AD cases are of late onset (LOAD) after age 65 years. LOAD shows complex, nonmendelian patterns of inheritance, and most likely results from the combined effects of variation in a number of genes as well as from environmental factors (summary by Grupe et al., 2006). The Alzheimer disease-6 (AD6) designation refers to a susceptibility locus on chromosome 10q. Although significant associations with several candidate genes on chromosome 10 have been reported, these findings have not been consistently replicated, and they remain controversial (Grupe et al., 2006). For a discussion of genetic heterogeneity of Alzheimer disease, see 104300.
DFNB26M is characterized by normal hearing despite the presence of homozygosity for a causative deafness mutation in the GAB1 gene (Yousaf et al., 2018).
DFNB26 is characterized by prelingual severe to profound nonsyndromic hearing loss (Yousaf et al., 2018).
Doing or saying again; a repeated performance.
A type of Developmental delay characterized by a delay in acquiring motor skills.
Disorder with characteristics of reduced pilosity over the scalp and body (with sparse, thin, and short hair) in the absence of other anomalies. Prevalence is unknown but numerous large pedigrees with several affected members have been described. Both men and women are equally affected. Hair loss is diffuse and progressive and usually begins during early childhood. Body hair may also be sparse with variable involvement of the eyebrows, eyelashes, and pubic and axillary hair. There are no anomalies of the skin, nails or teeth. A scalp-limited form has also been reported with mutations in the corneodesmosin (CDSN) gene. Both autosomal dominant and recessive modes of transmission have been reported for this disorder.
Mutations in the CHMP4B gene have been found to cause multiple types of cataract, which have been described as posterior polar, progressive posterior subcapsular, nuclear, and anterior subcapsular. The preferred title/symbol of this entry was formerly 'Cataract, Posterior Polar, 3; CTPP3.'
Repeated episodes of headache with rapid onset, reaching a peak within minutes and of short duration (less than one hour) with pain that is throbbing, pulsating, or bursting in quality.
Recurrent attacks of severe anxiety, whose occurence is not restricted to any particular situation or set of circumstances and is therefore unpredictable.
Spinocerebellar ataxia type 14 (SCA14) is characterized by slowly progressive cerebellar ataxia, dysarthria, and nystagmus. Axial myoclonus, cognitive impairment, tremor, and sensory loss may also be observed. Parkinsonian features including rigidity and tremor have been described in some families. Findings seen in other ataxia disorders (e.g., dysphagia, dysphonia) may also occur in SCA14. Age of onset ranges from childhood to the sixth decade. Life span is not shortened.
A decrease in the ability to perceive vibration at the ankles. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to the malleoli of the ankles.
An abnormal predominance of type I muscle fibers (in general, this feature can only be observed on muscle biopsy).
Naevus flammeus localised in the skin of the eyelid.
Macrocephaly/autism syndrome is an autosomal dominant disorder characterized by increased head circumference, abnormal facial features, and delayed psychomotor development resulting in autistic behavior or mental retardation (Herman et al., 2007). Some patients may have a primary immunodeficiency disorder with recurrent infections associated with variably abnormal T- and B-cell function (Tsujita et al., 2016).
The postnatal development of an abnormally large skull (macrocephaly).
A narrowing of the biparietal diameter (i.e., of the transverse distance between the protuberances of the two parietal bones of the skull).
HMSNR is an autosomal recessive progressive complex peripheral neuropathy characterized by onset in the first decade of distal lower limb weakness and muscle atrophy resulting in walking difficulties. Distal impairment of the upper limbs usually occurs later, as does proximal lower limb weakness. There is distal sensory impairment, with pes cavus and areflexia. Laboratory studies suggest that it is a myelinopathy resulting in reduced nerve conduction velocities in the demyelinating range as well as a length-dependent axonopathy (summary by Sevilla et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive hereditary motor and sensory neuropathy, also known as Charcot-Marie-Tooth disease, see CMT4A (214400).
The presence of axonal regeneration following a previous axonal lesion.
Noonan syndrome (NS) is a multiple congenital anomalies syndrome characterized by a typical face, congenital heart disease, and short stature (summary by van der Burgt and Brunner, 2000). For a general phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950).
Severely hypoplastic and triangular-shaped tibiae and absence of the fibulae.Two sporadic cases have been described. Moderate mesomelia of the upper limbs, proximal widening of the ulnas, pelvic anomalies and marked bilateral glenoid hypoplasia also reported.
In the families described to date, the phenotype of spinocerebellar ataxia type 13 (SCA13) has ranged from slowly progressive childhood-onset cerebellar gait ataxia associated with cerebellar dysarthria and often accompanied by mild intellectual disability and occasional seizures to adult-onset progressive ataxia. Life span is not shortened and many persons live beyond age 70 years, but assistance with gait may be required as the disease progresses.
A type of dysmetria involving the limbs.
Recurrent infection of the gastrointestinal tract.
Abnormality affecting one or more of the cranial nerves, which emerge directly from the brain stem. [HPO:probinson]
An autosomal dominant disorder characterized by the triad of thrombocytopenia, giant platelets, and characteristic inclusions in peripheral blood leukocytes, without other organ dysfunction; it is associated with mutation of the MYH9 gene.
Wiedemann-Steiner syndrome is a congenital malformation syndrome characterized by hypertrichosis cubiti associated with short stature; consistent facial features, including long eyelashes, thick or arched eyebrows with a lateral flare, wide nasal bridge, and downslanting and vertically narrow palpebral fissures; mild to moderate intellectual disability; behavioral difficulties; and hypertrichosis on the back (summary by Jones et al., 2012 and Miyake et al., 2016).
Fasciculations affecting the musculature of the arms and legs.
A rare congenital myopathy syndrome characterised by nonprogressive myopathy (manifesting with mild facial and generalised weakness, bilateral ptosis, and severe lumbar lordosis), severe intellectual disability, short stature, and sexual infantilism (due to hypogonadotropic hypogonadism). The presence of a small pituitary fossa was also noted. There have been no further descriptions in the literature since 1985.
Autosomal recessive lethal congenital contracture syndrome (LCCS) is the most severe, neonatally lethal, form of arthrogryposis (see 108120), a disorder characterized by congenital nonprogressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth (summary by Markus et al., 2012). Genetic Heterogeneity of Lethal Congenital Contracture Syndrome See also lethal congenital contracture syndrome-2 (LCCS2; 607598), caused by mutation in the ERBB3 gene (190151); LCCS3 (611369), caused by mutation in the PIP5K1C gene (606102); LCCS4 (614915), caused by mutation in the MYBPC1 gene (160794); LCCS5 (615368), caused by mutation in the DNM2 gene (602378); LCCS6 (616248), caused by mutation in the ZBTB42 gene (613915); LCCS7 (616286), caused by mutation in the CNTNAP1 gene (602346); LCCS8 (616287), caused by mutation in the ADCY6 gene (600294); LCCS9 (616503), caused by mutation in the ADGRG6 gene (612243); LCCS10 (617022), caused by mutation in the NEK9 gene (609798); and LCCS11 (617194), caused by mutation in the GLDN gene (608603).
Multiple pterygium syndrome is a condition that is evident before birth with webbing of the skin (pterygium) at the joints and a lack of muscle movement (akinesia) before birth. Akinesia frequently results in muscle weakness and joint deformities called contractures that restrict the movement of joints (arthrogryposis). As a result, multiple pterygium syndrome can lead to further problems with movement such as arms and legs that cannot fully extend.The two forms of multiple pterygium syndrome are differentiated by the severity of their symptoms. Multiple pterygium syndrome, Escobar type (sometimes referred to as Escobar syndrome) is the milder of the two types. Lethal multiple pterygium syndrome is fatal before birth or very soon after birth.In people with multiple pterygium syndrome, Escobar type, the webbing typically affects the skin of the neck, fingers, forearms, inner thighs, and backs of the knee. People with this type may also have arthrogryposis. A side-to-side curvature of the spine (scoliosis) is sometimes seen. Affected individuals may also have respiratory distress at birth due to underdeveloped lungs (lung hypoplasia). People with multiple pterygium syndrome, Escobar type usually have distinctive facial features including droopy eyelids (ptosis), outside corners of the eyes that point downward (downslanting palpebral fissures), skin folds covering the inner corner of the eyes (epicanthal folds), a small jaw, and low-set ears. Males with this condition can have undescended testes (cryptorchidism). This condition does not worsen after birth, and affected individuals typically do not have muscle weakness later in life.Lethal multiple pterygium syndrome has many of the same signs and symptoms as the Escobar type. In addition, affected fetuses may develop a buildup of excess fluid in the body (hydrops fetalis) or a fluid-filled sac typically found on the back of the neck (cystic hygroma). Individuals with this type have severe arthrogryposis. Lethal multiple pterygium syndrome is associated with abnormalities such as underdevelopment (hypoplasia) of the heart, lung, or brain; twisting of the intestines (intestinal malrotation); kidney abnormalities; an opening in the roof of the mouth (a cleft palate); and an unusually small head size (microcephaly). Affected individuals may also develop a hole in the muscle that separates the abdomen from the chest cavity (the diaphragm), a condition called a congenital diaphragmatic hernia. Lethal multiple pterygium syndrome is typically fatal in the second or third trimester of pregnancy.
Diffuse unlocalised atrophy affecting the cerebellum.
A deformity of the sella turcica whereby the sella extends further anterior than normal such that the anterior clinoid process appears to overhang it, giving the appearance of the letter J on imaging of the skull.
Some or all of the metacarpal bones (i.e., metacarpal II to V) have a pointed proximal appearance.
An increased concentration of dermatan sulfate in the urine.
The presence of wide, concave anterior rib ends.
A grey discoloration of the dental enamel.
All of the metacarpal bones of the hand have a pointed proximal appearance.
An increased concentration of heparan sulfates in the urine.
An abnormal increase of density of the bones making up the calvaria.
Complete lack of development of speech and language abilities.
Defective structure and function of myelin sheaths of the white matter of the brain.
Mucolipidosis III gamma (ML III gamma) is a slowly progressive disorder characterized by childhood onset of radiographic evidence of mild to moderate dysostosis multiplex; joint stiffness and pain initially in the shoulders, hips, and fingers; and gradual mild coarsening of facial features. Cardiorespiratory complications (restrictive lung disease, thickening and insufficiency of the mitral and aortic valves, left ventricular hypertrophy) can be significant. A few affected individuals have mild cognitive impairment. Because ML III gamma has only recently been distinguished from the more common ML III alpha/beta, previously published descriptions of ML III may have inadvertently included both of these disorders. Thus, much is to yet be learned about the specific manifestations and natural history of ML III gamma.
An increased rate of iduronate-2-sulfatase activity in the blood.
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
A thrusting or bulging out of the abdomen.
A reduction of the distance between the lower thoracic vertebral pedicles.
The presence of short and wide phalanges which taper distally (""bullet shaped"").
Familial monosomy 7 is characterized by early-childhood onset of bone marrow insufficiency/failure associated with increased risk for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). In all reported individuals, the monosomy 7 is believed to be an acquired cytogenetic abnormality within hematopoietic cells due to as-yet poorly defined inherited genetic predisposition. Identification of peripheral blood leukocytes with monosomy 7 usually precedes bone marrow failure/MDS/AML by a few months to years. Nearly all individuals reported with familial monosomy 7 have died of their disease. Note: Only a minority of individuals with bone marrow failure/MDS/AML with monosomy 7 have familial monosomy 7.
Molybdenum cofactor deficiency is a rare condition characterized by brain dysfunction (encephalopathy) that worsens over time. Babies with this condition appear normal at birth, but within a week they have difficulty feeding and develop seizures that do not improve with treatment (intractable seizures). Brain abnormalities, including deterioration (atrophy) of brain tissue, lead to severe developmental delay; affected individuals usually do not learn to sit unassisted or to speak. A small percentage of affected individuals have an exaggerated startle reaction (hyperekplexia) to unexpected stimuli such as loud noises. Other features of molybdenum cofactor deficiency can include a small head size (microcephaly) and facial features that are described as ""coarse.""Tests reveal that affected individuals have high levels of chemicals called sulfite, S-sulfocysteine, xanthine, and hypoxanthine in the urine and low levels of a chemical called uric acid in the blood.Because of the serious health problems caused by molybdenum cofactor deficiency, affected individuals usually do not survive past early childhood.
Molybdenum cofactor deficiency is a rare autosomal recessive metabolic disorder characterized by neonatal onset of intractable seizures, opisthotonus, and facial dysmorphism associated with hypouricemia and elevated urinary sulfite levels. Affected individuals show severe neurologic damage and often die in early childhood (summary by Reiss et al., 1999). For a general phenotypic description and a discussion of genetic heterogeneity of MOCOD, see MOCODA (252150), which is clinically indistinguishable from MOCODB.
Agenesis of one or more central incisors, i.e., of lower secondary incisor, lower primary incisor, upper secondary incisor, or of upper central primary incisor.
Mitochondrial complex II deficiency is an autosomal recessive disorder with a highly variable phenotype. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Measurement of complex II activity in muscle is the most reliable means of diagnosis; however, there is no clear correlation between residual complex II activity and severity or clinical outcome. In some cases, treatment with riboflavin may have clinical benefit (summary by Jain-Ghai et al., 2013).
Loss of developmental skills, as manifested by loss of developmental milestones.
Leukoencephalopathy that gets more severe with time.
Microphthalmia designates a heterogeneous group of ocular malformations with a more or less evident reduction in the size of the eyeball. Additional features include high hypermetropia and a short axial length. The size of the anterior chamber and the cornea may also be reduced, whereas the lens is normal or thicker than usual for age (summary by Fuchs et al., 2005). Genetic Heterogeneity of Isolated Microphthalmia MCOP1 has been mapped to chromosome 14q32. MCOP2 (610093) is caused by mutation in the CHX10 gene (142993) on chromosome 14q24. MCOP3 (611038) is caused by mutation in the RAX gene (601881) on chromosome 18q21.3. MCOP4 (613094) is caused by mutation in the GDF6 gene (601147) on chromosome 8q22.1. MCOP5 (611040) is caused by mutation in the MFRP gene (606227) on chromosome 11q23. MCOP6 (613517) is caused by mutation in the PRSS56 gene (613858) on chromosome 2q37.1. MCOP7 (613704) is caused by mutation in the GDF3 gene (606522) on chromosome 12p13.1. MCOP8 (615113) is caused by mutation in the ALDH1A3 gene (600463) on chromosome 15q26.
An abnormal decrease from the normal count of B cells.
Deaths that occur before LIFE EXPECTANCY is reached within a given population.
Microcephaly-micromelia syndrome (MIMIS) is a severe autosomal recessive disorder that usually results in death in utero or in the perinatal period. Affected individuals have severe growth retardation with microcephaly and variable malformations of the limbs, particularly the upper limbs. Defects include radial ray anomalies, malformed digits, and clubfeet (summary by Evrony et al., 2017).
Syndrome with characteristics of severe intellectual deficit, microcephaly and dilated cardiomyopathy. Hand and foot anomalies have also been reported. The syndrome has been described in three individuals. Transmission is autosomal recessive.
Primary microcephaly refers to the clinical finding of a head circumference more than than 3 standard deviations (SD) below the age- and sex-related mean, present at birth. Primary microcephaly is a static developmental anomaly, distinguished from secondary microcephaly, which refers to a progressive neurodegenerative condition. Microcephaly is a disorder of fetal brain growth; individuals with microcephaly have small brains and almost always have mental retardation, although rare individuals with mild microcephaly (-3 SD) and normal intelligence have been reported. Additional clinical features may include short stature or mild seizures. MCPH is associated with a simplification of the cerebral cortical gyral pattern and a slight reduction in the volume of the white matter, consistent with the small size of the brain, but the architecture of the brain in general is normal, with no evidence of a neuronal migration defect (review by Woods et al., 2005). Most cases of primary microcephaly show an autosomal recessive mode of inheritance. Because MCPH directly affects neurogenesis, or neurogenic mitosis, rather than growth of the skull, some prefer the term 'micrencephaly' (Hofman, 1984). MCPH1 in particular is associated with premature chromosome condensation in cell studies (Darvish et al., 2010). Genetic Heterogeneity of Primary Microcephaly Primary microcephaly is a genetically heterogeneous disorder. See MCPH2 (604317), caused by mutation in the WDR62 gene (613583) on chromosome 19q13; MCPH3 (604804), caused by mutation in the CDK5RAP2 gene (608201) on 9q33; MCPH4 (604321), caused by mutation in the CASC5 gene (609173) on 15q14; MCPH5 (608716), caused by mutation in the ASPM gene (605481) on 1q31; MCPH6 (608393), caused by mutation in the CENPJ gene (609279) on 13q12; MCPH7 (612703), caused by mutation in the STIL gene (181590) on 1p33; MCPH8 (614673), caused by mutation in the CEP135 gene (611423) on 4q12; MCPH9 (614852), caused by mutation in the CEP152 gene (613529) on 15q21; MCPH10 (615095), caused by mutation in the ZNF335 gene (610827) on 20q13; MCPH11 (615414), caused by mutation in the PHC1 gene (602978) on 12p13; MCPH12 (616080), caused by mutation in the CDK6 gene (603368) on 7q21; MCPH13 (616051), caused by mutation in the CENPE gene (117143) on 4q24; MCPH14 (616402), caused by mutation in the SASS6 gene (609321) on 1p21; MCPH15 (616486), caused by mutation in the MFSD2A gene (614397) on 1p34; MCPH16 (616681), caused by mutation in the ANKLE2 gene (616062) on 12q24; MCPH17 (617090), caused by mutation in the CIT gene (605629) on 12q24; MCPH18 (617520), caused by mutation in the WDFY3 gene (617485) on 4q21; and MCPH19 (617800), caused by mutation in the COPB2 gene (606990) on 3q23; MCPH20 (617914), caused by mutation in the KIF14 gene (611279) on 1q31; MCPH21 (617983), caused by mutation in the NCAPD2 gene (615638) on 12p13; MCPH22 (617984), caused by mutation in the NCAPD3 gene (609276) on 11q25; MCPH23 (617985), caused by mutation in the NCAPH gene (602332) on 2q11; MCPH24 (618179), caused by mutation in the NUP37 gene (609264) on 12q23; and MCPH25 (618351), caused by mutation in the MAP11 gene (618350) on 7q22.
Growth retardation with prenatal onset, cataracts, microcephaly, intellectual deficit, immune deficiency, delayed ossification and enamel hypoplasia. Transmission is autosomal recessive.
Hypoplastic (short) proximal phalanx of the thumb. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Onset of signs or symptoms of disease within the first 28 days of life.
Increased concentration of methylmalonic acid in the urine.
The category of 3-methylglutaconic aciduria type IV (MGCA4) represents a heterogeneous unclassified group of patients who share mild or intermittent urinary excretion of 3-methylglutaconic acid. MGCA excretion is a nonspecific finding observed in many other disorders caused by defects in mitochondrial energy metabolism (Gunay-Aygun, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA1 (250950)
Metaphyseal cupping affecting the metacarpal bones.
Abnormally flat configuration of the glenoid fossa, also known as the glenoid cavity, which is the articular surface of the scapula that articulates with the head of the humerus.
A polar cataract that affects the anterior pole of the lens.
Irregularity of the iliac crest, which is the superior border of the wing of the ilium.
Increased side-to-side width of one or more phalanges of the fingers or toes.
Progressive bending or abnormal curvature of the leg.
An immunodeficiency characterized by defective cell-mediated immunity or humoral immunity.
Increased susceptibility to chicken pox, as manifested by recurrent episodes of chicken pox.
Developmental delay of ossification of the proximal epiphysis of the femur.
Sedaghatian-type spondylometaphyseal dysplasia (SMDS) is a rare lethal disorder characterized by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, delayed epiphyseal ossification, irregular iliac crests, and pulmonary hemorrhage. Affected infants present with severe hypotonia and cardiorespiratory problems; most die within days of birth due to respiratory failure. Cardiac abnormalities include conduction defects, complete heart block, and structural anomalies. Half of infants with SMDS are reported to have central nervous system malformations consistent with abnormal neuronal migration, including agenesis of the corpus callosum, pronounced frontotemporal pachygyria, simplified gyral pattern, partial lissencephaly, and severe cerebellar hypoplasia (summary by Smith et al., 2014).
A congenital absence of the convolutions of the cerebral cortex and a poorly formed sylvian fissure that affects a particular part of the cortex.
An enlargement of the posterior fontanelle relative to age-dependent norms.
A cone-shaped appearance of the epiphyses of the metacarpal bones, producing a 'ball-in-a-socket' appearance. This epiphyses are located at the distal ends of the metacarpal bones.
A type of disproportionate short stature characterized by disproportionate shortening of the medial parts of the extremities (forearm or lower leg).
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective). [pmid:19152421]
Forearm shortening because of underdevelopment of one or more bones of the forearm.
Absence of the proximal radial epiphysis.
This syndrome has characteristics of moderate intellectual deficit, craniofacial dysmorphism, hypergonadotropic hypogonadism, eunuchoid habitus, type 1 diabetes mellitus, and epilepsy. It has been described in four patients (three brothers and their sister). This syndrome is probably transmitted as an autosomal recessive trait.
The primary characteristics of the Frank-ter Haar syndrome are brachycephaly, wide fontanels, prominent forehead, hypertelorism, prominent eyes, macrocornea with or without glaucoma, full cheeks, small chin, bowing of the long bones, and flexion deformity of the fingers. Protruding, simple ears and prominent coccyx are also regarded as important diagnostic signs (summary by Maas et al., 2004). Borrone syndrome was described as a severe progressive multisystem disorder with features overlapping those of FTHS, including thick skin, acne conglobata, osteolysis, gingival hypertrophy, brachydactyly, camptodactyly, and mitral valve prolapse. Although it was initially thought to be a distinct phenotype, mutations in the FTHS-associated gene SH3PXD2B have been identified in patients diagnosed with Borrone syndrome. The earlier differential description was attributed to phenotypic variability as well as to differences in the ages at which patients were examined (Wilson et al., 2014).
Underdevelopment of part or all of the external reproductive organs.
Underdevelopment of the urinary bladder.
A bending or abnormal curvature of a long bone.
Mast syndrome is an autosomal recessive complicated form of hereditary spastic paraplegia in which progressive spastic paraparesis is associated in more advanced cases with cognitive decline, dementia, and other neurologic abnormalities. Symptom onset usually occurs in adulthood, and the disorder is progressive with variable severity. Brain imaging shows thinning of the corpus callosum. The disorder occurs with high frequency in the Old Order Amish (summary by Simpson et al., 2003). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
A syndrome marked by marfanoid habitus (tall stature with long and slim limbs, little subcutaneous fat, arachnodactyly, joint hyperextensibility, narrow face, small chin, large testes, and hypotonia) associated with microcephaly and glomerulonephritis.
Underdevelopment of the inferior portion of the vermis of cerebellum.
A pathologic fibrous band that impedes passage of intestinal contents through the duodenum.
The presence of an increased number of twists and turns of the conjunctival blood vessels.
A moderate form recognized before age ten years with presence of skeletal abnormalities, myopathy, and slow progression.
Hyperconvexity of the thoracolumbar spine producing a rounded or humped appearance.
Manitoba oculotrichoanal (MOTA) syndrome is characterized by an aberrant hairline (unilateral or bilateral wedge-shaped extension of the anterior hairline from the temple region to the ipsilateral eye) and anomalies of the eyes (ocular hypertelorism, anophthalmia/microphthalmia, cryptophthalmos, colobomas of the upper eyelid and corneopalpebral synechiae), nose (bifid or wide with a notched tip), abdominal wall (omphalocele or umbilical hernia), and anus (stenosis and/or anterior displacement of the anal opening). The manifestations and degree of severity vary even among affected members of the same family. Growth and psychomotor development are normal.
HOMG5 is an autosomal recessive disorder characterized by severe renal magnesium wasting, progressive renal failure, nephrocalcinosis, and severe visual impairment (Konrad et al., 2006). Amelogenesis imperfecta may also be present in some patients (Yamaguti et al., 2017). For a discussion of genetic heterogeneity of renal hypomagnesemia, see 602014.
A very rare ectodermal dysplasia syndrome, described in 2 adult brothers, characterised by the association of hypoparathyroidism, nephropathy, congenital lymphoedema, mitral valve prolapse and brachytelephalangy. Additional features include mild facial dysmorphism, hypertrichosis and nail abnormalities.
An abnormal increase in the carrying angle, which is the angle he long axis of the extended forearm as it lies lateral to the long axis of the arm.
Abnormal dilatation of the pulmonary lymphatic vessels. Lymphatic fluid in the lung is derived from normal leakage of fluid out of the blood capillaries in the lung. In pulmonary lymphangiectasia, the pulmonary lymphatics are not properly connected and become dilated with fluid.
Depression of profile in both temporal regions.
A rare disorder caused by mutation in the LMF1 gene resulting in combined lipase deficiency with concomitant hypertriglyceridemia and associated disorders.
FATCO syndrome comprises fibular aplasia, tibial campomelia, and oligosyndactyly (Courtens et al., 2005). See also ectrodactyly (split-hand/foot malformation) associated with fibular hypoplasia/aplasia (113310).
Syndrome with characteristics of frequent infections associated with osteoporosis, a tendency for fractures and osseous anomalies. It has been described in two monozygotic twin brothers. Transmission is autosomal recessive.
Abnormally high BLOOD GLUCOSE level after a meal.
A face that is short (HP:0011219) and narrow (HP:0000275).
Abnormal increase in size of one or more metaphyses.
A very rare syndrome described in four siblings of one French family and with characteristics of branchial dysplasia (malar hypoplasia, macrostomia, preauricular tags and meatal atresia), club feet, inguinal hernia and cholestasis due to paucity of interlobular bile ducts and intellectual deficit.
A rare metabolic myopathy with characteristics of muscle cramping and/or stiffness after exercise (especially during heat exposure), post-exertional rhabdomyolysis and myoglobinuria and elevation of serum creatine kinase. Caused by mutation in the SLC16A1 gene.
Sudden and involuntary contractions of one or more muscles brought on by physical exertion.
A type of muscle stiffness that occurs following physical exertion.
An abnormally increased tendency towards muscle fatigue induced by physical exercise.
Keutel syndrome is an autosomal recessive disorder characterized by multiple peripheral pulmonary stenoses, brachytelephalangy, inner ear deafness, and abnormal cartilage ossification or calcification (summary by Khosroshahi et al., 2014).
Calcification of the costal cartilages, which are bars of hyaline cartilage found at the anterior ends of the ribs which serve to prolong the ribs forward and contribute to the elasticity of the walls of the thorax.
Fusion of the epiphysis and metaphysis of one or more phalanges prior to the normal age or stage of growth.
Ossification affecting the set of cartilages of larynx.
Haim-Munk syndrome is an autosomal recessive disorder characterized by palmoplantar keratoderma, severe periodonitis, arachnodactyly, acroosteolysis, atrophic changes of the nails, and a radiographic deformity of the fingers (summary by Hart et al., 2000).
An autosomal recessive form of Kenny-Caffey syndrome due to mutation(s) in the TBCE gene, encoding tubulin-specific chaperone E. This condition is characterized by hypoparathyroidism with hypocalcemia, marked growth retardation, craniofacial anomalies, absent diploic space in the skull, cortical thickening of long bones with medullary stenosis, and small hands and feet.
A fetus that does not grow beyond the 10th percentile of conventionally accepted weight for gestational age.
An increase in bone density affecting the calvaria (roof of the skull).
Kaufman oculocerebrofacial syndrome (KOS) is characterized by severe intellectual disability and distinctive craniofacial features. Most affected children have prenatal-onset microcephaly, failure to thrive, hypotonia, and short stature. Eye abnormalities are common and can include structural abnormalities (microcornea or microphthalmia, coloboma, optic nerve hypoplasia), refractive errors (myopia ± astigmatism, hyperopia), strabismus, and entropion. Less common findings can include: unilateral or bilateral conductive hearing loss or mixed conductive-sensorineural hearing loss of variable severity; congenital heart defects; breathing problems; feeding difficulties; urogenital abnormalities; and/or skeletal abnormalities.
When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval. [HPO:probinson]
Any abnormality of the cornea, which is the transparent tissue at the front of the eye that covers the iris, pupil, and anterior chamber.
Absence or underdevelopment of the vermis of cerebellum. [HPO:curators]
A developmental structural anomaly of the stalk-like part of the brain that comprises the midbrain (aka mesencephalon), the pons (aka pons Varolii), and the medulla oblongata, and connects the cerebral hemispheres with the cervical spinal cord.
Lack of any response to stimulation upon electroretinography.
Developmental hypoplasia of the primary teeth.
A developmental defect resulting in the congenital absence of skin on the scalp.
Stromme syndrome is an autosomal recessive congenital disorder affecting multiple systems with features of a ciliopathy. Affected individuals typically have some type of intestinal atresia, variable ocular abnormalities, microcephaly, and sometimes involvement of other systems, including renal and cardiac. In some cases, the condition is lethal in early life, whereas other patients show normal survival with or without mild cognitive impairment (summary by Filges et al., 2016).
A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.
Baraitser-Winter syndrome is a condition that affects the development of many parts of the body, particularly the face and the brain.An unusual facial appearance is the most common characteristic of Baraitser-Winter syndrome. Distinctive facial features can include widely spaced eyes (hypertelorism), large eyelid openings, droopy eyelids (ptosis), high-arched eyebrows, a broad nasal bridge and tip of the nose, a long space between the nose and upper lip (philtrum), full cheeks, and a pointed chin.Structural brain abnormalities are also present in most people with Baraitser-Winter syndrome. These abnormalities are related to impaired neuronal migration, a process by which nerve cells (neurons) move to their proper positions in the developing brain. The most frequent brain abnormality associated with Baraitser-Winter syndrome is pachygyria, which is an area of the brain that has an abnormally smooth surface with fewer folds and grooves. Less commonly, affected individuals have lissencephaly, which is similar to pachygyria but involves the entire brain surface. These structural changes can cause mild to severe intellectual disability, developmental delay, and seizures.Other features of Baraitser-Winter syndrome can include short stature, ear abnormalities and hearing loss, heart defects, presence of an extra (duplicated) thumb, and abnormalities of the kidneys and urinary system. Some affected individuals have limited movement of large joints, such as the elbows and knees, which may be present at birth or develop over time. Rarely, people with Baraitser-Winter syndrome have involuntary muscle tensing (dystonia).
Hair on the neck extends more inferiorly than usual.
An abnormal deviation from normal levels of immunoglobulins in blood.
A developmental anomaly with lateral displacement of the femoral head.
Less than normal number of natural killer cells, a type of lymphocyte in the innate immune system that contains cytoplasmic granzymes, i.e., small granules with perforin and proteases that allow natural killer cells to form pores in the cell membrane of the target cell through which the granzymes and associated molecules can enter, inducing apoptosis. [HPO:probinson]
Vici syndrome is a rare congenital multisystem disorder characterized by agenesis of the corpus callosum (ACC), cataracts, pigmentary defects, progressive cardiomyopathy, and variable immunodeficiency. Affected individuals also have profound psychomotor retardation and hypotonia due to a myopathy (summary by Finocchi et al., 2012).
Inability to react to a delayed hypersensitivity skin test.
An ectodermal dysplasia syndrome characterised by severe generalised lamellar icthyosis at birth with alopecia, eclabium, ectropion and intellectual disability. Although similar to Sjogren-Larsson syndrome, this syndrome lacks the presence of neurologic or macular changes. There have been no further descriptions in the literature since 1987.
A minor variant of autosomal recessive congenital ichthyosis with manifestation of a collodion membrane at birth that heals within the first weeks of life. The exact prevalence is unknown. Approximately 25 cases have been reported in the literature. After the shedding of the membrane, patients present with mild scaling. Caused by mutations in the TGM1, ALOXE3 or ALOX12B genes encoding respectively transglutaminase 1, involved in the cornification of the stratum corneum, and arachidonate 3 and 12(R) lipoxygenases involved in lipid metabolism. Transmission is autosomal recessive.
A very rare syndrome of congenital hypothyroidism with characteristics of thyroid dysgenesis, cleft palate and spiky hair, with or without choanal atresia, and bifid epiglottis. Facial dysmorphism and porencephaly have been reported in isolated cases. Only 8 patients from 6 families have been reported to date. Newborns present at birth with thyroid dysgenesis (in most cases athyreosis) leading to congenital hypothyroidism that manifests with lethargy, poor feeding, macroglossia, cold or mottled skin, persistent jaundice and umbilical hernia. All newborns have a cleft palate and spiky hair. The syndrome is due to homozygous loss-of-function missense mutations located within the forkhead domain of the FOXE1 gene (9q22), encoding thyroid transcription factor 2 (TTF-2). TTF-2 is expressed in the thyroid gland (as well as elsewhere like the tongue, epiglottis and palate) and is thought to play a crucial role in thyroid morphogenesis. The disease is inherited autosomal recessively.
The presence of calcium-containing calculi (stones) in the kidneys.
Schisis (cleft or cleavage) of vertebral bodies.
HRDS is an autosomal recessive multisystem disorder characterized by intrauterine and postnatal growth retardation, infantile-onset hypoparathyroidism that can result in severe hypocalcemic seizures, dysmorphic facial features, and developmental delay (summary by Padidela et al., 2009 and Ratbi et al., 2015).
Intrauterine growth retardation that is 4 or more standard deviations below average, corrected for sex and gestational age.
Patchy (irregular) increase in bone density. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Hypomandibular faciocranial syndrome consists of craniosynostosis, prominent eyes, deficient midface and zygomatic arches, short nose with anteverted nares, protruding lower face, minute oral aperture, persistent buccopharyngeal membrane, severe mandibular hypoplasia, and various extracephalic anomalies (summary by Gorlin et al., 2001).
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, 607364) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Diffusely large eye (with megalocornea) without glaucoma. [HPO:probinson]
An impairment in the rate and degree to which platelets aggregate after the addition of an agonist that stimulates platelet clumping. Platelet aggregation is measured using aggregometer to measure the optical density of platelet-rich plasma, whereby platelet aggregation causes the plasma to become more transparent.
Syndrome with the association of hypergonadotropic hypogonadism and cataracts with onset during adolescence. It has been described in three brothers from a consanguineous family. An autosomal recessive mode of transmission appears likely.
Glycogen storage disease type 0 (also known as GSD 0) is a condition caused by the body's inability to form a complex sugar called glycogen, which is a major source of stored energy in the body. GSD 0 has two types: in muscle GSD 0, glycogen formation in the muscles is impaired, and in liver GSD 0, glycogen formation in the liver is impaired.The signs and symptoms of muscle GSD 0 typically begin in early childhood. Affected individuals often experience muscle pain and weakness or episodes of fainting (syncope) following moderate physical activity, such as walking up stairs. The loss of consciousness that occurs with fainting typically lasts up to several hours. Some individuals with muscle GSD 0 have a disruption of the heart's normal rhythm (arrhythmia) known as long QT syndrome. In all affected individuals, muscle GSD 0 impairs the heart's ability to effectively pump blood and increases the risk of cardiac arrest and sudden death, particularly after physical activity. Sudden death from cardiac arrest can occur in childhood or adolescence in people with muscle GSD 0.Individuals with liver GSD 0 usually show signs and symptoms of the disorder in infancy. People with this disorder develop low blood sugar (hypoglycemia) after going long periods of time without food (fasting). Signs of hypoglycemia become apparent when affected infants begin sleeping through the night and stop late-night feedings; these infants exhibit extreme tiredness (lethargy), pale skin (pallor), and nausea. During episodes of fasting, ketone levels in the blood may increase (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars (such as glycogen) are unavailable. These short-term signs and symptoms of liver GSD 0 often improve when food is eaten and sugar levels in the body return to normal. The features of liver GSD 0 vary; they can be mild and go unnoticed for years, or they can include developmental delay and growth failure.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inherited condition that affects many of the body's organs. It is one of many autoimmune diseases, which are disorders that occur when the immune system malfunctions and attacks the body's own tissues and organs by mistake.In most cases, the signs and symptoms of APECED begin in childhood or adolescence. This condition commonly involves three characteristic features: chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal gland insufficiency. Affected individuals typically have at least two of these features, and many have all three.CMC is a tendency to develop infections of the skin, the nails, and the moist lining of body cavities (mucous membranes) caused by a type of fungus called Candida. These infections, which are commonly known as yeast infections, are chronic, which means they recur and can last a long time. CMC is usually the first of the three characteristic features of APECED to become apparent in people with this disorder. Almost all affected individuals develop infections of the oral cavity (known as thrush). Infections of the tube that carries food from the mouth to the stomach (the esophagus) are also common, while the skin and nails are affected less often. In women, vaginal infections frequently occur.Other features of APECED result from the body's immune system attacking the network of hormone-producing glands (the endocrine system). The second characteristic feature of the disorder is hypoparathyroidism, which is a malfunction of the parathyroid glands. These glands secrete a hormone that regulates the body's use of calcium and phosphorus. Damage to the parathyroid glands leads to reduced parathyroid hormone production (hypoparathyroidism). Hypoparathyroidism can cause a tingling sensation in the lips, fingers, and toes; muscle pain and cramping; weakness; and fatigue.Damage to the small hormone-producing glands on top of each kidney (adrenal glands) results in a third major feature of APECED, adrenal gland insufficiency (Addison disease). Reduced hormone production by the adrenal glands leads to signs and symptoms that can include fatigue, muscle weakness, loss of appetite, weight loss, low blood pressure, and changes in skin coloring. Other endocrine problems that can occur in APECED include type 1 diabetes resulting from impaired production of the hormone insulin; a shortage of growth hormone leading to short stature; problems affecting the internal reproductive organs (ovaries or testes) that can cause inability to conceive children (infertility); and dysfunction of the thyroid gland (a butterfly-shaped tissue in the lower neck), which can result in many symptoms including weight gain and fatigue.Autoimmune problems affecting non-endocrine tissues can lead to a variety of additional signs and symptoms in people with APECED. These features occur more often in North American populations than in European populations. Rashes that resemble hives (urticarial eruptions) are common and often occur in infancy and early childhood. Other early signs and symptoms may include thin enamel on the teeth (enamel hypoplasia) and chronic diarrhea or constipation associated with difficulty in absorbing nutrients from food. Additional features that occur in people with APECED, many of which can lead to permanent organ and tissue damage if left untreated, include stomach irritation (gastritis), liver inflammation (hepatitis), lung irritation (pneumonitis), dry mouth and dry eyes (Sjogren-like syndrome), inflammation of the eyes (keratitis), kidney problems (nephritis), vitamin B12 deficiency, hair loss (alopecia), loss of skin color in blotches (vitiligo), high blood pressure (hypertension), or a small (atrophic) or absent spleen (asplenia).
Increased side-to-side width of the first metatarsal bone.
A confluent, generalized overgrowth of silvery blonde to gray lanugo hair at birth.
A very rare syndrome associating an acro-fronto-facio-nasal dysostosis with genitourinary anomalies. It has been described in three families. Craniofacial manifestations include wide anterior fontanelle, flat occiput, hypertelorism, ptosis, proptosis, broad nasal bridge and nasal tip, long philtrum and posteriorly rotated or low set ears. Hypospadias and shawl scrotum are present in all males. Acral manifestations include syndactyly of fingers, broad thumbs or halluces or preaxial polydactyly. The affected patients have no intellectual deficit. The condition seems to be hereditary, and transmitted as an autosomal recessive trait.
Mabry syndrome is a condition characterized by intellectual disability, distinctive facial features, increased levels of an enzyme called alkaline phosphatase in the blood (hyperphosphatasia), and other signs and symptoms.People with Mabry syndrome have intellectual disability that is often moderate to severe. They typically have little to no speech development and are delayed in the development of motor skills (such as sitting, crawling, and walking). Many affected individuals have low muscle tone (hypotonia) and develop recurrent seizures (epilepsy) in early childhood. Seizures are usually the generalized tonic-clonic type, which involve muscle rigidity, convulsions, and loss of consciousness.Individuals with Mabry syndrome have distinctive facial features that include wide-set eyes (hypertelorism), long openings of the eyelids (long palpebral fissures), a nose with a broad bridge and a rounded tip, downturned corners of the mouth, and a thin upper lip. These facial features usually become less pronounced over time.Hyperphosphatasia begins within the first year of life in people with Mabry syndrome. There are many different types of alkaline phosphatase found in tissues; the type that is increased in Mabry syndrome is called the tissue non-specific type and is found throughout the body. In affected individuals, alkaline phosphatase levels in the blood are usually increased by one to two times the normal amount, but can be up to 20 times higher than normal. The elevated enzyme levels remain relatively stable over a person's lifetime. Hyperphosphatasia appears to cause no negative health effects, but this finding can help health professionals diagnose Mabry syndrome.Another common feature of Mabry syndrome is shortened bones at the ends of fingers (brachytelephalangy), which can be seen on x-ray imaging. Underdeveloped fingernails (nail hypoplasia) may also occur. Sometimes, individuals with Mabry syndrome have abnormalities of the digestive system, including narrowing or blockage of the anus (anal stenosis or anal atresia) or Hirschsprung disease, a disorder that causes severe constipation or blockage of the intestine. Rarely, affected individuals experience hearing loss.The signs and symptoms of Mabry syndrome vary among affected individuals. Those who are least severely affected have only intellectual disability and hyperphosphatasia, without distinctive facial features or the other health problems listed above.
Farsightedness, also known as hyperopia, is an eye condition that causes blurry near vision. People who are farsighted have more trouble seeing things that are close up (such as when reading or using a computer) than things that are far away (such as when driving).For normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. Some people who are farsighted have eyeballs that are too short from front to back. Others have a cornea or lens that is abnormally shaped. These changes cause light entering the eye to be focused too far back, behind the retina instead of on its surface. It is this difference that causes nearby objects to appear blurry. In a person with this condition, one eye may be more farsighted than the other.If it is not treated with corrective lenses or surgery, farsightedness can lead to eye strain, excess tearing, squinting, frequent blinking, headaches, difficulty reading, and problems with hand-eye coordination. However, some children with the eye changes characteristic of farsightedness do not notice any blurring of their vision or related signs and symptoms early in life. Other parts of the visual system are able to compensate, at least temporarily, for the changes that would otherwise cause light to be focused in the wrong place.Most infants are born with a mild degree of farsightedness, which goes away on its own as the eyes grow. In some children, farsightedness persists or is more severe. Children with a severe degree of farsightedness, described as high hyperopia, are at an increased risk of developing other eye conditions, particularly ""lazy eye"" (amblyopia) and eyes that do not look in the same direction (strabismus). These conditions can cause significant visual impairment.In general, older adults also have difficulty seeing things close up; this condition is known as presbyopia. Presbyopia develops as the lens of the eye becomes thicker and less flexible with age and the muscles surrounding the lens weaken. Although it is sometimes described as ""farsightedness,"" presbyopia is caused by a different mechanism than hyperopia and is considered a separate condition.
2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA).The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory. Researchers have described two subtypes of D-2-HGA, type I and type II. The two subtypes are distinguished by their genetic cause and pattern of inheritance, although they also have some differences in signs and symptoms. Type II tends to begin earlier and often causes more severe health problems than type I. Type II may also be associated with a weakened and enlarged heart (cardiomyopathy), a feature that is typically not found with type I.L-2-HGA particularly affects a region of the brain called the cerebellum, which is involved in coordinating movements. As a result, many affected individuals have problems with balance and muscle coordination (ataxia). Additional features of L-2-HGA can include delayed development, seizures, speech difficulties, and an unusually large head (macrocephaly). Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood.Combined D,L-2-HGA causes severe brain abnormalities that become apparent in early infancy. Affected infants have severe seizures, weak muscle tone (hypotonia), and breathing and feeding problems. They usually survive only into infancy or early childhood.
A severe loss of myelin from nerve fibers in the central nervous system.
Abnormal development of the adrenal gland.
An abnormality of the gyri (i.e., the ridges) of the cerebral cortex of the brain.
An abnormality of the vagina. [HPO:probinson]
A multiple congenital anomalies syndrome described in two sisters and with the presence of hydrocephalus (onset in infancy), tall stature, joint laxity, and thoracolumbar kyphosis. There have been no further descriptions in the literature since 1989.
A rare developmental disorder described in 4 siblings so far. Main characteristics include delayed fetal growth, hydrocephaly with patent aqueduct of Sylvius, underdeveloped lungs and various other anomalies such as small jaw, intestinal malrotation, shortness of lower limbs, bowed tibias and foot deformities.
MARCH is an autosomal recessive lethal congenital disorder characterized by severe hydranencephaly with almost complete absence of the cerebral hemispheres, which are replaced by fluid, relative preservation of the posterior fossa structures, and renal dysplasia or agenesis. Affected fetuses either die in utero or shortly after birth, and show arthrogryposis and features consistent with anhydramnios. Histologic examination of residual brain tissue shows multinucleated neurons resulting from impaired cytokinesis (summary by Frosk et al., 2017).
Methylenetetrahydrofolate reductase deficiency is a common inborn error of folate metabolism. The phenotypic spectrum ranges from severe neurologic deterioration and early death to asymptomatic adults. In the classic form, both thermostable and thermolabile enzyme variants have been identified (Rosenblatt et al., 1992).
Methylenetetrahydrofolate Reductase (MTHFR) Deficiency is the most common genetic cause of elevated levels of homocysteine in the plasma (hyperhomocysteinemia). The MTHFR enzyme plays an important role in processing amino acids, specifically, the conversion of homocysteine to methionine. Genetic variations in the MTHFR gene can lead to impaired function or inactivation of this enzyme, which results in mildly elevated levels of homocysteine, especially in individuals who are also deficient in folate. In these individuals, a daily supplement of low dose folic acid may reduce and often normalize their homocysteine levels, but this has not been demonstrated to improve health outcomes. A common genetic variant in the MTHFR gene is a 677C>T polymorphism (NM_005957.4:c.665C>T, rs1801133). This variant encodes a thermolabile enzyme that is less active at higher temperatures. Individuals who carry two copies of this variant (“TT homozygous”) tend to have higher homocysteine levels and lower serum folate levels compared to controls. More than 25% of Hispanics and around 10-15% of North America Caucasians are estimated to be homozygous for the “thermolabile” variant (TT genotype). The TT genotype is least common in individuals of African descent (6%). Another common MTHFR variant, 1298A>C (NM_005957.4:c.1286A>C, rs1801131), does not cause increased homocysteine levels in heterozygous or homozygous individuals, but combined heterozygosity of 1298A>C and 677C>T results in an outcome similar to TT homozygous individuals. Until recently, it was thought that MTHFR deficiency, by causing elevated homocysteine levels, led to an increased risk of venous thrombosis, coronary heart disease, and recurrent pregnancy loss. However, more recent analysis has not found an association between elevated homocysteine levels and the risk of venous thrombosis or the risk of coronary heart disease. MTHFR polymorphism genotyping should not be ordered as part of the clinical evaluation for thrombophilia, recurrent pregnancy loss, or for at-risk family members. Rarely, more severe variants in the MTHFR gene can be a cause of an autosomal recessive inborn error or metabolism where extremely high levels of homocysteine accumulate in the urine and plasma. This can cause developmental delay, eye disorders, thrombosis, and osteoporosis. But more commonly, homocystinuria is caused by variants in a different gene (cystathionine beta-synthase, CBS).
Homocystinuria due to methylene tetrahydrofolate reductase (MTHFR) deficiency is a metabolic disorder characterised by neurological manifestations.
Exaggerated concavity of the anterior or posterior surface of the vertebral body, i.e., the upper and lower vertebral endplates are hollowed inward.
Mowat-Wilson syndrome (MWS) is characterized by the following: Distinctive facial features. Structural anomalies including: Hirschsprung disease. Genitourinary anomalies (particularly hypospadias in males). Congenital heart defects (particularly abnormalities of the pulmonary arteries and/or valves). Agenesis or hypogenesis of the corpus callosum. Eye defects (microphthalmia and Axenfeld anomaly). Functional differences including: Moderate to severe intellectual disability. Severe speech impairment with relative preservation of receptive language. Seizures. Growth retardation with microcephaly. Chronic constipation in those without Hirschsprung disease.
A conspicuously happy disposition with frequent smiling and laughing that may be context-inappropriate or unrelated to context.
An abnormal orientation of the earlobes such that they point out- and upward. That is, the lateral surface of ear lobe faces superiorly.
Columella extending inferior to the level of the nasal base, when viewed from the side.
Regional increase in the width (height) of the eyebrow.
An anomalous origin of the left pulmonary artery, such that it arises from the posterior aspect of the right pulmonary artery and passes between the trachea and esophagus to reach the left hilum.
Congenital bile acid synthesis defect type 2 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Bile is used during digestion to absorb fats and fat-soluble vitamins, such as vitamins A, D, E, and K. People with congenital bile acid synthesis defect type 2 cannot produce (synthesize) bile acids, which are a component of bile that stimulate bile flow and help it absorb fats and fat-soluble vitamins. As a result, an abnormal form of bile is produced.The signs and symptoms of congenital bile acid synthesis defect type 2 often develop in infancy. Affected infants usually have a failure to gain weight and grow at the expected rate (failure to thrive) and yellowing of the skin and eyes (jaundice) due to impaired bile flow and a buildup of partially formed bile. Excess fat in the feces (steatorrhea) is another feature of congenital bile acid synthesis defect type 2. As the condition progresses, affected individuals can develop liver abnormalities including inflammation or chronic liver disease (cirrhosis). Some individuals with congenital bile acid synthesis defect type 2 cannot absorb certain fat-soluble vitamins, which can result in softening and weakening of the bones (rickets) or problems with blood clotting that lead to prolonged bleeding.If left untreated, congenital bile acid synthesis defect type 2 typically leads to cirrhosis and death in childhood.
Hepatic veno-occlusive disease with immunodeficiency (VODI) is characterized by: (1) primary immunodeficiency; and (2) terminal hepatic lobular vascular occlusion and hepatic fibrosis manifest as hepatomegaly and/or hepatic failure. Onset is usually before age six months. The immunodeficiency comprises severe hypogammaglobulinemia, clinical evidence of T-cell immunodeficiency with normal numbers of circulating T cells, absent lymph node germinal centers, and absent tissue plasma cells. Bacterial and opportunistic infections including Pneumocystis jirovecii infection, mucocutaneous candidiasis, and enteroviral or cytomegalovirus infections occur. In the past the prognosis for affected individuals was poor, with 100% mortality in the first year of life if unrecognized and untreated with intravenous immunoglobulin (IVIG) and Pneumocystis jirovecii prophylaxis. However, with early recognition and treatment there is a marked improvement in prognosis.
The presence of lymphangiectasis of the thyroid gland.
An abnormal conical morphology of the incisor tooth.
An abnormal dilatation of lymph vessels in the pericardium.
The presence of lymphangiectasis in the pancreas.
Isolated hemihyperplasia is an abnormality of cell proliferation leading to asymmetric overgrowth of one or more regions of the body. The term 'hemihyperplasia' has replaced the term 'hemihypertrophy' to describe accurately the increase in cell number found in these patients. The incidence of isolated hemihyperplasia is estimated to be 1 in 86,000. Idiopathic hemihypertrophy is associated with increased risk of embryonal cancers in childhood, particularly Wilms tumor (194070) (Shuman et al., 2006). Hoyme et al. (1998) provided an anatomic classification of hemihyperplasia: complex hemihyperplasia is involvement of half of the body, including at least 1 arm and 1 leg; affected parts may be contralateral or ipsilateral. Simple hemihyperplasia is involvement of a single limb. See also facial hemihyperplasia (133900). Although isolated hemihyperplasia is a distinct clinical entity, it can also occur as a feature of overgrowth syndromes, including Beckwith-Wiedemann syndrome (BWS; 130650), neurofibromatosis (NF1; 162200), Proteus syndrome (176920), and Klippel-Trenaunay-Weber syndrome (149000) (Shuman et al., 2006).
This syndrome is characterised by sensorineural hearing loss, generalised enamel hypoplasia of the permanent dentition with normal primary dentition and nail defects (Beau's lines and leukonychia). Less than 10 patients have been described so far. Transmission is autosomal recessive.
Gentle upward curve of the upper lip vermilion such that the center is placed well superior to the commissures.
A less than normal number of sternal ossification centers. The sternum is initially formed from bilateral sternal plates that chondrify and begin to fuse with ribs at 10 weeks gestational age. Ossification starts in the manubrium and upper part of the sternal body at the 6th month, in the middle of the sternal body at the 7th month, in the lower part of the body during the 1st postnatal year and in the xiphoid process between years 5 and 18. The number of ossification centers vary up to six, and it is the ossification centers that are visualized by prenatal ultrasound. This term describes a reduction in the number of ossification centers compared with age-related norms.
The presence of an abnormally thin calvarium.
Syndrome with the association of stubby, coarse, sparse and fragile hair, eyebrows and eyelashes with photosensitivity and nonprogressive intellectual deficit, without a demonstrable metabolic aberration. It has been described in three sisters born to consanguineous parents.
Congenital grouped pigmentation of the retina is a rare disorder characterized by a grouping together of round to oval spots of pigment in one or more quadrants of the retina, except for the macula (summary by Renardel de Lavalette et al., 1991).
Immunodeficiency-59 is an autosomal recessive primary immunologic disorder characterized by combined immunodeficiency and recurrent septic infections of the respiratory tract, skin, and mucous membranes, as well as disturbed glucose metabolism. Granulocytopenia and B-cell and dentritic cell deficiency are present (Haapaniemi et al., 2017).
Premature closure of the coronal suture of skull.
An association syndrome described only once in two sisters. They had a 46,XY karyotype, cleft lip and palate, preauricular pits and a 'squashed down' appearance because of a short columella and small nares. Other anomalies included broad hands and feet, and a hypermuscular appearance. Cardiac, renal, musculoskeletal and ectodermal anomalies were also present. Ectodermal defects included 'punched out scalp defects' and unusual positioning of hair whorls. They also had short stature, streak gonads, and mild developmental delay.
Nonsyndromic disorders of testicular development are a group of conditions characterized by the following: A generally normal physical examination with absence of clinical findings involving organ systems other than the reproductive organs. A normal 46,XY karyotype by conventional staining. External genitalia that range from ambiguous to normal female. Internal genitalia that range from absent müllerian structures to a fully developed uterus and fallopian tubes. Gonads that are characterized as normal testis, ovotestis, dysgenetic testis, or streak. Based on the particular features seen in any given individual, the clinical diagnosis may be designated as 46,XY disorder of sex development (DSD) or 46,XY complete gonadal dysgenesis (CDG).
An increase in the amount of glycogen stored in hepatocytes compared to normal.
A characteristic facial appearance with a round facial form, full cheeks, a short nose, and a relatively small chin.
Two forms of glutathione synthetase deficiency have been described; a mild form, referred to as glutathione synthetase deficiency of erythrocytes, causing hemolytic anemia, and a more severe form causing 5-oxoprolinuria with secondary neurologic involvement (266130).
Encephalopathy with onset in the infantile period.
An increased concentration of dicarboxylic acid in the urine.
A decreased concentration of glucose in the blood associated with a reduced concentration of ketone bodies.
Ghosal hematodiaphyseal dysplasia is a rare inherited condition characterized by abnormally thick bones and a shortage of red blood cells (anemia). Signs and symptoms of the condition become apparent in early childhood.In affected individuals, the long bones in the arms and legs are unusually dense and wide. The bone changes specifically affect the shafts of the long bones, called diaphyses, and areas near the ends of the bones called metaphyses. The bone abnormalities can lead to bowing of the legs and difficulty walking.Ghosal hematodiaphyseal dysplasia also causes scarring (fibrosis) of the bone marrow, which is the spongy tissue inside long bones where blood cells are formed. The abnormal bone marrow cannot produce enough red blood cells, which leads to anemia.Signs and symptoms of anemia that have been reported in people with Ghosal hematodiaphyseal dysplasia include extremely pale skin (pallor) and excessive tiredness (fatigue).
The facial appearance is more circular than usual as viewed from the front.
An abnormally slow velocity of horizontal saccadic eye movements.
Saccadic undershoot of horizontal saccadic eye movements, i.e., a horizontal saccadic eye movement that has less than the magnitude that would be required to gain fixation of the object.
Abnormal calcification of a cardiac valve.
Gaucher disease is an inherited disorder that affects many of the body's organs and tissues. The signs and symptoms of this condition vary widely among affected individuals. Researchers have described several types of Gaucher disease based on their characteristic features.Type 1 Gaucher disease is the most common form of this condition. Type 1 is also called non-neuronopathic Gaucher disease because the brain and spinal cord (the central nervous system) are usually not affected. The features of this condition range from mild to severe and may appear anytime from childhood to adulthood. Major signs and symptoms include enlargement of the liver and spleen (hepatosplenomegaly), a low number of red blood cells (anemia), easy bruising caused by a decrease in blood platelets (thrombocytopenia), lung disease, and bone abnormalities such as bone pain, fractures, and arthritis.Types 2 and 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by problems that affect the central nervous system. In addition to the signs and symptoms described above, these conditions can cause abnormal eye movements, seizures, and brain damage. Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy. Type 3 Gaucher disease also affects the nervous system, but it tends to worsen more slowly than type 2.The most severe type of Gaucher disease is called the perinatal lethal form. This condition causes severe or life-threatening complications starting before birth or in infancy. Features of the perinatal lethal form can include extensive swelling caused by fluid accumulation before birth (hydrops fetalis); dry, scaly skin (ichthyosis) or other skin abnormalities; hepatosplenomegaly; distinctive facial features; and serious neurological problems. As its name indicates, most infants with the perinatal lethal form of Gaucher disease survive for only a few days after birth.Another form of Gaucher disease is known as the cardiovascular type because it primarily affects the heart, causing the heart valves to harden (calcify). People with the cardiovascular form of Gaucher disease may also have eye abnormalities, bone disease, and mild enlargement of the spleen (splenomegaly).
Abnormally decreased rate of beta-galactosidase activity. Beta-galactosidase activity can be measured in leukocyte, fibroblast, or plasma.
The presence of foam cells in the bone marrow, generally demonstrated by bone-marrow aspiration or biopsy. Foam cells have a vacuolated appearance due to the presence of complex lipid deposits, giving them a foamy or soap-suds appearance.
Anterior tongue-like protrusions of the vertebral bodies.
Gamma-glutamylcysteine synthetase deficiency is 1 of 4 diseases involving enzymes in the gamma-glutamyl cycle (Meister, 1974). The other 3 disorders are glutathione synthetase deficiency (231900), 5-oxoprolinuria, which is a severe or generalized form of glutathione synthetase deficiency (266130), and gamma-glutamyl transpeptidase deficiency (231950). All except gamma-glutamyl transpeptidase deficiency are accompanied by hemolytic anemia (Larsson and Anderson, 2001).
Ribs that are increased in width and taper to the posterior ends.
Aplasia or hypoplasia of the paranasal sinuses.
A flattened vertebral body shape with reduced distance between the vertebral endplates affecting the cervical spine.
An increased concentration of chloride in the sweat.
Polysplenia is a congenital disease manifested by multiple small accessory spleens.
An abnormality of the helix. The helix is the outer rim of the ear that extends from the insertion of the ear on the scalp (root) to the termination of the cartilage at the earlobe.
Reduced transparency of the stroma of cornea.
A loss or impairment of the sensation of the relative position of parts of the body and joint position.
Inability to elicit tendon reflexes in the lower limbs.
Subnormal concentration of follicle stimulating hormone (FSH), associated with mutations in the FSHB gene, encoding follitropin subunit beta.
Familial benign fleck retina is an autosomal recessive condition associated with a distinctive retinal appearance and no apparent visual or electrophysiologic deficits. Affected individuals are asymptomatic, but fundus examination reveals a striking pattern of diffuse, yellow-white, fleck-like lesions extending to the far periphery of the retina but sparing the foveal region (summary by Sergouniotis et al., 2011).
This syndrome has features of fibuloulnar dysostosis with renal anomalies. It has been described in two siblings born to nonconsanguinous parents. The syndrome is lethal at birth (respiratory failure). Clinical manifestations include ear and facial anomalies (including micrognathia), symmetrical shortness of long bones, fibular agenesis and hypoplastic ulna, oligosyndactyly, congenital heart defects, and cystic or hypoplastic kidney. It is transmitted as an autosomal recessive trait.
This syndrome has main characteristics of bowing of the femora, aplasia or hypoplasia of the fibulae and poly, oligo and syndactyly. It has been reported in 11 patients. Most of the patients also had a hypoplastic pelvis and hypoplasia of the fingers and fingernails. Some had congenital dislocation of the hip, absence or fusion of tarsal bones, absence of various metatarsals and hypoplasia and aplasia of the toes. The syndrome is caused by a partial loss of WNT7A function (gene mapped to 3p25).
Absence or underdevelopment of the fibula.
Severe reduction or absence of the fibula and complex brachydactyly. The syndrome is inherited in an autosomal recessive manner and is caused by mutations in the cartilage-derived morphogenetic protein-1 gene.
Malalignement of carpal bone angles either with respect to each other, to the corresponding metacarpals or with respect to the wrist (radius and ulna).
Absence or underdevelopment of the toenail.
The presence of a coronal suture (the cranial suture that separates the frontal and parietal bones) that is not ossified but rather wide open at an age when it is normally closed.
The presence of a sagittal suture (the cranial suture that separates the left and right parietal bones) that is not ossified but rather wide open at an age when it is normally closed.
A very rare malformation with main features of ectrodactyly of the hand and ipsilateral bifurcation of the femur. Approximately 200 cases have been reported worldwide. Congenital aplasia/hypoplasia of the tibia, accompanied by pre-axial oligodactyly or monodactyly of the feet, may also be present. In most cases, the bifurcation of the distal femur is unilateral. Patients are often small. Autosomal dominant and autosomal recessive modes of transmission have been suggested.
A very rare syndrome including short stature, facial dysmorphism, hand abnormalities and shawl scrotum. It has been observed in 16 subjects from five distantly related sibships of a large Kuwaiti Bedouin tribe. The affected patients had no intellectual deficit. Transmitted as an autosomal recessive trait.
The ability of the joints of the hand to move beyond their normal range of motion.
An inherited bleeding disorder caused by the reduction in activity and antigen levels of both factor V and factor VIII with manifestation of mild-to-moderate bleeding symptoms. Caused by mutations either in the LMAN1 gene (chromosome 18; q21) or in the MCFD2 gene (chromosome 2). Transmission is autosomal recessive.
Syndactyly with fusion of fingers three and four.
Lethal faciocardiomelic dysplasia is an extremely rare polymalformative syndrome. It was described only once, in 1975, in 3 affected males in a sibship of 13, from second-cousin parents. Patients were all of low birth weight, had microretrognathia, microstomia, and microglossia, hypoplasia of the radius and ulna with radial deviation of the hands, simian creases and hypoplasia of fingers I and V, hypoplasia of the fibula and tibia with talipes and wide space between toes I and II, and severe malformation of the left heart which may have been responsible for death of all 3 in the first week or so of life.
Genetic Heterogeneity of Variation in Skin/Hair/Eye Pigmentation Multiple genes influence normal human skin, hair, and/or eye pigmentation. Pigmentation phenotypes influenced by variation in the OCA2 gene are termed SHEP1. The SHEP2 association (266300) is determined by variation at the MC1R locus (155555) and describes a phenotype predominantly characterized by red hair and fair skin. SHEP3 (601800) encompasses pigment variation influenced by the TYR gene (606933); SHEP4 (113750), that influenced by the SLC24A5 gene (609802). Variation in the SLC45A2 (606202) and SLC24A4 (609840) genes result in the phenotypic associations SHEP5 (227240) and SHEP6 (210750), respectively. Sequence variation thought to affect expression of KITLG (184745) results in the SHEP7 (611664) phenotypic association. SHEP8 (611724) is associated with variation in the IRF4 gene (601900). Polymorphism in the 3-prime untranslated region of the ASIP gene (600201) influences the SHEP9 association (611742). The SHEP10 association (612267) comprises variation in the TPCN2 gene (612163), and SHEP11 (612271) is associated with polymorphism near the TYRP1 gene (115501).
A rare skin disorder characterised by erythrodermic peeling skin from birth with no obvious nail or hair-shaft abnormalities and other associated anomalies including diarrhoea, failure to thrive and severe hypoalbuminaemia resistant to correction by enteral or intravenous supplementation. An autosomal recessive mode of inheritance is highly probable. The prognosis is poor and infants die in the first months of life. There have been no further descriptions in the literature since 1992.
Reduced number of beta cells in the pancreatic islets of Langerhans.
Sclerosis of the epiphyses, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Short (hypoplastic middle phalanx of finger, affecting all fingers.
An anomaly of the patella characterized by two layers visible on lateral knee X-ray such that one layer is in front of the other in the sagittal orientation (See Figure 2A and 3B of PMID:12966518). This finding persists into adulthood.
Epidermolysis bullosa with pyloric atresia (EB-PA) is characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma; congenital pyloric atresia; and ureteral and renal anomalies (dysplastic/multicystic kidney, hydronephrosis/hydroureter, ureterocele, duplicated renal collecting system, absent bladder). The course of EB-PA is usually severe and often lethal in the neonatal period. Most affected children succumb as neonates; those who survive may have severe blistering with formation of granulation tissue on the skin around the mouth, nose, fingers, and toes, and internally around the trachea. However, some affected individuals have little or no blistering later in life. Additional features shared by EB-PA and the other major forms of EB include congenital localized absence of skin (aplasia cutis congenita) affecting the extremities and/or head, milia, nail dystrophy, scarring alopecia, hypotrichosis, contractures, and dilated cardiomyopathy.
Hyperkeratosis affecting the sole of the foot.
The proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome is a rare, autosomal recessive, usually prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. It is usually diagnosed by ultrasound between 26 and 33 weeks' gestation (summary by Meyer et al., 2010). Rarely, affected individuals may survive, but are severely impaired with almost no neurologic development (Kvarnung et al., 2016).
Multiple areas of darker than expected signal on magnetic resonance imaging emanating from the deep cerebral white matter.
Increased concentration of interferon alpha in the cerebrospinal fluid (CSF).
Recurrent partial dislocations of the mandible.
Pneumothorax occurring neonatally without traumatic injury to the chest or lung.
A progressive form of scoliosis with congenital onset.
Ehlers-Danlos syndrome, cardiac valvular type is a form of Ehlers-Danlos syndrome characterized by soft skin, skin hyperextensibility, easy bruisability, atrophic scar formation, joint hypermobility and cardiac valvular defects comprising mitral and/or aortic valve insufficiency.
Syndrome with the association of ectodermal dysplasia, ectrodactyly, and macular dystrophy. So far, it has been described in individuals from seven families. Hypotrichosis, dental anomalies and absent eyebrows have also been reported. Appears to be transmitted as an autosomal recessive trait and may be caused by mutations in the cadherin-3 gene (CH3, 16q22.1).
Decreased number of head hairs per unit area.
Progressively reduced or lacking hair growth.
Lack of formation of mineralized bony tissue of the sternum.
IWith incomplete partition II, the cochlea consists of 1.5 turns; the apical and middle cochlea turns are undifferentiated and form a cystic apex. The vestibule is normal while the vestibular aqueduct is always enlarged. Developmental arrest occurs at the seventh week of gestation.
Absence or failure to form of the external auditory canal.
Torsion dystonia-2 is an autosomal recessive neurologic disorder characterized by onset of symptoms in childhood or adolescence. 'Dystonia' is characterized by involuntary, sustained muscle contractions affecting 1 or more sites of the body; 'torsion' refers to the twisting nature of body movements observed in dystonia. DYT2 first affects distal limbs and later involves the neck, orofacial, and craniocervical regions. DYT2 is slowly progressive but mild overall (summary by Muller and Kupke, 1990; Nemeth, 2002; Khan et al., 2003).
A rare genetic primary bone dysplasia and lethal form of neonatal short-limbed dwarfism, with characteristics of anisospondyly, severe short stature and limb shortening, metaphyseal flaring and distinct dysmorphic features (flat facial appearance, abnormal ears, short neck, narrow thorax). Additional features may include other skeletal findings (for example joint contractures, bowed limbs, talipes equinovarus) and urogenital and cardiovascular abnormalities.
Abnormally increased variability of the size of the vertebral bodies.
A reduction in the freedom of movement of one or more joints.
Parietal bossing is a marked prominence in the parietal region.
Progressive bending or abnormal curvature of a long bone.
An abnormality of the pattern of trabecula (small interconnecting rods of bone) in a metaphyseal region of bone.
Intermittent episodes of abnormally increased perspiration.
Abnormally increased size of the costochondral junctions, which are located between the distal part of the ribs and the costal cartilages, which are bars of hyaline cartilage that connect the ribs to the sternum.
Irregularities of the iliac crest that produce the appearance of a lace border around it.
Abnormally increased width of the pubic symphysis is the midline cartilaginous joint uniting the superior rami of the left and right pubic bones.
Decreased density/number and/or decreased diameter of lateral eyebrow hairs.
A very rare disorder with phocomelia of upper limbs, encephalocele, variable brain anomalies, urogenital abnormalities and thrombocytopenia. Less than 15 cases have been reported. The spectrum of upper limb defects varies from radial agenesis and phocomelia to amelia. A meningoencephalocele is constant. The intellectual development may be normal. Pathogenesis and cause of this syndrome are unknown. Parental consanguinity reported in a family suggests an autosomal recessive pattern of inheritance.
Rhizomelic chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized by disproportionately short stature primarily affecting the proximal parts of the extremities, a typical facial appearance including a broad nasal bridge, epicanthus, high-arched palate, dysplastic external ears, and micrognathia, congenital contractures, characteristic ocular involvement, dwarfism, and severe mental retardation with spasticity. Biochemically, plasmalogen synthesis and phytanic acid alpha-oxidation are defective. Most patients die in the first decade of life. RCDP1 (215100) is the most frequent form of RCDP (summary by Wanders and Waterham, 2005). Whereas RCDP1 is a peroxisomal biogenesis disorder (PBD), RCDP2 is classified as a single peroxisome enzyme deficiency (Waterham and Ebberink, 2012). For a discussion of genetic heterogeneity of rhizomelic chondrodysplasia punctata, see 215100.
DECR deficiency is a rare autosomal recessive inborn error of metabolism resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic dysfunction beginning in early infancy. Laboratory studies show decreased activity of the mitochondrial NADP(H)-dependent enzymes DECR1 (222745) and AASS (605113), resulting in increased C10:2-carnitine levels and hyperlysinemia (summary by Houten et al., 2014).
Characterised by infantile-onset hypoglycaemia and hyperprolinaemia associated, in certain cases, with intellectual deficit. Less than 10 cases have been reported to date. Defects in renal and intestinal glutamate and aspartate transport were also reported, suggesting that anomalies of the EAAC1 transporter, involved in the transport of these two amino acids, are the underlying cause of this syndrome.
Although the spectrum of phenotypic expression in trichohepatoenteric syndrome (THES) is broad, the characteristic features include intrauterine growth retardation, woolly hair, facial dysmorphism, intractable diarrhea in infancy requiring total parenteral nutrition, and immunodepression. Hepatic involvement contributes to the poor prognosis of affected patients (summary by Fabre et al., 2007). Genetic Heterogeneity of Trichohepatoenteric Syndrome Trichohepatoenteric syndrome-2 (THES2; 614602) is caused by mutation in the SKIV2L gene (600478) on chromosome 6p21.
Donnai-Barrow syndrome (DBS) is characterized by typical craniofacial features (large anterior fontanel, wide metopic suture, widow's peak, markedly widely spaced eyes, enlarged globes, downslanted palpebral fissures, posteriorly rotated ears, depressed nasal bridge, and short nose. Ocular complications include high myopia, retinal detachment, retinal dystrophy, and progressive vision loss. Additional common features include agenesis of the corpus callosum, sensorineural hearing loss, intellectual disability, and congenital diaphragmatic hernia and/or omphalocele. Both inter- and intrafamilial phenotypic variability are observed.
Skin crease extending from below the inner canthus laterally along the malar process of the maxilla and zygoma.
Congenital diaphragmatic hernia is a defect in the diaphragm. The diaphragm, which is composed of muscle and other fibrous tissue, separates the organs in the abdomen from those in the chest. Abnormal development of the diaphragm before birth leads to defects ranging from a thinned area in the diaphragm to its complete absence. An absent or partially formed diaphragm results in an abnormal opening (hernia) that allows the stomach and intestines to move into the chest cavity and crowd the heart and lungs. This crowding can lead to underdevelopment of the lungs (pulmonary hypoplasia), potentially resulting in life-threatening breathing difficulties that are apparent from birth.In 5 to 10 percent of affected individuals, signs and symptoms of congenital diaphragmatic hernia appear later in life and may include breathing problems or abdominal pain from protrusion of the intestine into the chest cavity. In about 1 percent of cases, congenital diaphragmatic hernia has no symptoms; it may be detected incidentally when medical imaging is done for other reasons.Congenital diaphragmatic hernias are often classified by their position. A Bochdalek hernia is a defect in the side or back of the diaphragm. Between 80 and 90 percent of congenital diaphragmatic hernias are of this type. A Morgnani hernia is a defect involving the front part of the diaphragm. This type of congenital diaphragmatic hernia, which accounts for approximately 2 percent of cases, is less likely to cause severe symptoms at birth. Other types of congenital diaphragmatic hernia, such as those affecting the central region of the diaphragm, or those in which the diaphragm muscle is absent with only a thin membrane in its place, are rare.
No consensus exists on what a stroke-like episode is, but these episodes can be functionally defined as a new neurological deficit, occurring with or without the context of seizures, which last longer than 24 hours.
Disease with characteristics of recurrent skin ulceration, arthralgia, fever, peri-articular osteolysis, oligodontia and nail dystrophy. This disease has been described in five siblings in a family of Kirghizian origin (Central Asia). Three of the siblings also presented with keratitis leading to visual impairment or blindness. Transmission is autosomal recessive.
Chronic loss of joint motion in a finger due to structural changes in non-bony tissue.
A cataract that affects the anterior part of the cortex of the lens.
This syndrome is characterised by the association of a progressive leukodystrophy marked by generalised mental and motor impairment with the presence of thickened and wrinkled skin. It has been described in a Japanese brother and sister born to healthy parents. Both patients died in early childhood.
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures (resulting from radiologically demonstrable polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages: (1) The latent stage is characterized by normal early development. (2) The osseous stage (3rd decade of life) is characterized by pain and tenderness, mostly in ankles and feet, usually following strain or injury. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities. (3) In the early neurologic stage (4th decade of life), a change of personality begins to develop insidiously. Affected individuals show a frontal lobe syndrome (loss of judgment, euphoria, loss of social inhibitions, disturbance of concentration, and lack of insight, libido, and motor persistence) leading to serious social problems. (4) The late neurologic stage is characterized by progressive dementia and loss of mobility. Death usually occurs before age 50 years.
Rare syndrome with manifestation of sensorineural hearing loss and oligodontia/hypodontia. It has been described in two pairs of siblings and in one isolated case. Transmission appears to be autosomal recessive.
Syndrome with characteristics of progressive sensorineural deafness, progressive sensory neuropathy and gastrointestinal abnormalities (progressive loss of gastric motility, small bowel diverticulosis). It has been described in five patients (three sisters in a family and two sisters born to consanguineous parents). This syndrome is transmitted as an autosomal recessive trait.
A rare genetic ectodermal dysplasia syndrome with characteristics of conductive hearing loss due to atresia of the external auditory canal and the middle ear complicated by chronic infection, ptosis and skeletal anomalies (internal rotation of hips, dislocation of the radial heads and fifth finger clinodactyly). In addition, a thin, pinched nose, delayed hair growth and dysplastic teeth are associated. There have been no further descriptions in the literature since 1978.
An extremely rare genetic syndrome with clinical characteristics of split hand/split foot malformation and mild to moderate sensorineural hearing loss, sometimes associated with cleft palate and intellectual deficit. There is evidence this syndrome may be caused by homozygous mutation in the DLX5 gene on chromosome 7q21.
A syndromic disorder with the association between Dandy-Walker malformation and postaxial polydactyly as a major feature. The Dandy-Walker malformation has a variable expression and characteristics of a posterior fossa cyst communicating with the fourth ventricle, the partial or complete absence of the cerebellar vermis, and facultative hydrocephalus. Postaxial polydactyly includes tetramelic postaxial polydactyly of hands and feet with possible enlargement of the fifth metacarpal and metatarsal bones, as well as bifid fifth metacarpals.
A discrete posterior fossa cerebrospinal fluid (CSF) collection that does not communicate directly with the fourth ventricle.
The French Canadian type of Leigh syndrome is an autosomal recessive severe neurologic disorder with onset in infancy. Features include delayed psychomotor development, mental retardation, mild dysmorphic facial features, hypotonia, ataxia, and the development of lesions in the brainstem and basal ganglia. Affected individuals tend to have episodic metabolic and/or neurologic crises in early childhood, which often lead to early death (summary by Debray et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of Leigh syndrome, see 256000.
A genetic disorder characterized by impairment of the function of the proximal tubules of the kidney, which results in decreased reabsorption of electrolytes, glucose, amino acids, and other nutrients.
Ventriculomegaly with cystic kidney disease is a severe autosomal recessive developmental disorder characterized by onset in utero of dilated cerebral ventricles and microscopic renal tubular cysts. The pregnancies of affected individuals are associated with increased alpha-fetoprotein (AFP). Most affected pregnancies have been terminated (summary by Slavotinek et al., 2015). See also 602200 for a disorder characterized by ventriculomegaly and defects of the radius and kidney.
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an endogenous form of adrenal Cushing syndrome characterized by multiple bilateral adrenocortical nodules that cause a striking enlargement of the adrenal glands. Although some familial cases have been reported, the vast majority of AIMAH cases are sporadic. Patients typically present in the fifth and sixth decades of life, approximately 10 years later than most patients with other causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005). Approximately 10 to 15% of adrenal Cushing syndrome is due to primary bilateral ACTH-independent adrenocortical pathology. The 2 main subtypes are AIMAH and primary pigmented nodular adrenocortical disease (PPNAD, see 610489), which is often a component of the Carney complex (160980) and associated with mutations in the PRKAR1A gene (188830) on chromosome 17q23-q24. AIMAH is rare, representing less than 1% of endogenous causes of Cushing syndrome (Swain et al., 1998; Christopoulos et al., 2005). See also ACTH-independent Cushing syndrome (615830) due to somatic mutation in the PRKACA gene (601639). Cushing 'disease' (219090) is an ACTH-dependent disorder caused in most cases by pituitary adenomas that secrete excessive ACTH. Genetic Heterogeneity of ACTH-Independent Macronodular Adrenal Hyperplasia AIMAH2 (615954) is caused by germline mutation of 1 allele of the ARMC5 gene (615549) coupled with a somatic mutation in the other allele.
Absence or underdevelopment of the kidney.
A pattern of hair growth in which there is hair exnteding from the temples to the lateral eyebrows.
An abnormality of the morphology or structure of the middle ear.
Characterised by frontal encephalocoele, craniosynostosis, and developmental delay.
The presence of multiple areas of atresia affecting the small intestine.
Reduced distance from the anterior border of the naris to the subnasale.
Digits are disproportionately narrow (reduced girth) for the hand/foot size or build of the individual. [pmid:19125433]
Poorly defined or shallow palmar creases.
Ears that are low-set (HP:0000369) and posteriorly rotated (HP:0000358).
An extremely rare disorder found in less than ten patients worldwide with characteristics of congenital heart defect, sagittal craniosynostosis and severe developmental delay. Genital and renal anomalies, and various dysmorphic features may be present. Joint and palpebral abnormalities may also occur. The occurrence of the syndrome in a brother-sister sibship supports the hypothesis of autosomal recessive inheritance. Autosomal dominant inheritance and submicroscopic deletions have also been proposed as possible causes.
Excessive growth (overgrowth) of the facial bones, that is of the facial skeleton.
An abnormal conformation of the femur that becomes gradually enlarged towards the distal end. This feature affects the distal femoral metaphysis and epiphysis.
Uneven (irregular) increase in bone density of one or more of the phalanges of the hand.
Temtamy syndrome is a mental retardation/multiple congenital anomaly syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities, including abnormalities of the corpus callosum and thalamus (summary by Akizu et al., 2013).
Abnormal flatness (decreased height) of epiphyses.
A very rare syndrome characterised by poorly mineralised calvarium, facial dysmorphism, vertebral abnormalities and absent clavicles. Nine cases have been reported in the literature so far. Dysmorphic features include micrognathia, cleft palate, hypertelorism and upturned nares. Clavicular aplasia is constant and agenesis of cervical vertebral bodies is frequent. Intra uterine growth retardation is constant. It is most likely that the condition is hereditary, transmitted as an autosomal recessive trait. Prognosis is poor, the syndrome is almost always lethal soon after birth.
Corneal endothelial dystrophy is characterized by thickening and opacification of the cornea, altered morphology of the endothelium, and secretion of an abnormal collagenous layer at the Descemet membrane (summary by Vithana et al., 2006).
A degenerative corneal disorder characterised by the association of congenital hereditary endothelial dystrophy with progressive postlingual sensorineural hearing loss. The ocular manifestations include diffuse bilateral corneal oedema occurring with severe corneal clouding, blurred vision, visual loss and nystagmus. Caused by mutations in the SLC4A11 gene located at the CHED2 locus on chromosome 20p13p12.
Cornea plana is clinically characterized by reduced corneal curvature leading in most cases to hyperopia, hazy corneal limbus, and arcus lipoides at an early age. CNA2 is a severe form of the disorder, which is frequently associated with additional ocular manifestations (summary by Tahvanainen et al., 1996). For discussion of genetic heterogeneity of CNA, see CNA1 (121400).
A facial cleft characterized by involvment of the orbit. [PMID:2503273]
Amaurosis hypertrichosis is characterised by severe retinal dystrophy marked by visual impairment and profound photophobia without night blindness. Eye examination suggested a cone-rod type of congenital amaurosis. Trichomegaly, bushy eyebrows with synophyrys, and excessive facial and body hair were also reported. The syndrome has been described in two female cousins both born to consanguineous parents.
For children from birth to 4 years of age, the palm width is more than 2 SD below the mean; for children from 4 to 16 years of age the palm width is below the 5th centile; or, the width of the palm appears disproportionately narrow for its length.
Patchy loss of myelin from nerve fibers in the central nervous system.
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Severely slow or limited growth after birth, being four standard deviations or more below age- and sex-related norms.
Mottling (spots or blotches with different shades) of the retinal pigment epithelium, i.e., localized or generalized fundal pigment granularity associated with processes at the level of the retinal pigment epithelium.
Sclerosis of the epiphyses of the phalanges of the fingers, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
A reduction in the level of thymic horomone.
A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.
COACH syndrome is an autosomal recessive disorder characterized by mental retardation, ataxia due to cerebellar hypoplasia, and hepatic fibrosis. Other features, such as coloboma and renal cysts, may be variable. COACH syndrome is considered by some to be a subtype of Joubert syndrome (JBTS; see 213300) with congenital hepatic fibrosis. Identification of liver disease in these patients is critical because some may develop complications such as portal hypertension with fatal variceal bleeding (Brancati et al., 2009; Doherty et al., 2010).
Yunis-Varon syndrome is a severe autosomal recessive disorder characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss. Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. The disorder is usually lethal in infancy (summary by Campeau et al., 2013).
Absence of the clavicles as a developmental defect.
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Elongated and tortuous mesenteric veins, which comprise the inferior mesenteric vein and the superior mesenteric vein.
Telangiectasia (that is, the presence of small dilated superficial blood vessels) of the lips.
The presence of small (ca. 0.5-1.0 mm) dilated blood vessels near the surface of the mucous membranes of the palate.
Any anomaly in the process by which myelin sheaths are formed and maintained around neurons.
A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.
Hereditary angioedema type III is a rare disorder characterized clinically by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. HAE III occurs almost exclusively in women and is often precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). It differs from HAE types I and II (106100) in that both concentration and function of C1 inhibitor (C1NH; 606860) are normal (summary by Dewald and Bork, 2006).
Leber congenital amaurosis is an eye disorder that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this disorder typically have severe visual impairment beginning in infancy. The visual impairment tends to be stable, although it may worsen very slowly over time.Leber congenital amaurosis is also associated with other vision problems, including an increased sensitivity to light (photophobia), involuntary movements of the eyes (nystagmus), and extreme farsightedness (hyperopia). The pupils, which usually expand and contract in response to the amount of light entering the eye, do not react normally to light. Instead, they expand and contract more slowly than normal, or they may not respond to light at all. Additionally, the clear front covering of the eye (the cornea) may be cone-shaped and abnormally thin, a condition known as keratoconus.A specific behavior called Franceschetti's oculo-digital sign is characteristic of Leber congenital amaurosis. This sign consists of poking, pressing, and rubbing the eyes with a knuckle or finger. Researchers suspect that this behavior may contribute to deep-set eyes and keratoconus in affected children.In rare cases, delayed development and intellectual disability have been reported in people with the features of Leber congenital amaurosis. However, researchers are uncertain whether these individuals actually have Leber congenital amaurosis or another syndrome with similar signs and symptoms.At least 13 types of Leber congenital amaurosis have been described. The types are distinguished by their genetic cause, patterns of vision loss, and related eye abnormalities.
Neonatal diabetes mellitus with congenital hypothyroidism (NDH) syndrome is characterized by intrauterine growth retardation and onset of nonimmune diabetes mellitus within the first few weeks of life. Other features include renal parenchymal disease, primarily renal cystic dysplasia, and hepatic disease, with hepatitis in some patients and hepatic fibrosis and cirrhosis in others. Facial dysmorphism, when present, consistently involves low-set ears, epicanthal folds, flat nasal bridge, long philtrum, and thin upper lip. Most patients exhibit developmental delay (Dimitri et al., 2015).
3-Methylglutaconic aciduria type V is an autosomal recessive disorder characterized by the onset of dilated or noncompaction cardiomyopathy in infancy or early childhood. Many patients die of cardiac failure. Other features include microcytic anemia, growth retardation, mild ataxia, mild muscle weakness, genital anomalies in males, and increased urinary excretion of 3-methylglutaconic acid. Some patients may have optic atrophy or delayed psychomotor development (summary by Davey et al., 2006 and Ojala et al., 2012). For a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950).
Partial or complete wasting (loss) of dentate nucleus.
Kyphoscoliosis is a 3-dimensional deformity of spinal growth characterized by curvature in the coronal plane (scoliosis) in conjunction with thoracic kyphosis in excess of the normal range in the sagittal plane (summary by Miller et al., 2006).
Late-onset Fuchs endothelial corneal dystrophy (FECD) is a degenerative disorder affecting roughly 4% of the population older than 40 years. It is distinguished from other corneal disorders by the progressive formation of guttae, which are microscopic refractile excrescences of the Descemet membrane, a collagen-rich basal lamina secreted by the corneal endothelium. From onset, it usually takes 2 decades for FECD to impair endothelial cell function seriously, leading to stromal edema and impaired vision (Sundin et al., 2006). For a discussion of genetic heterogeneity of Fuchs endothelial corneal dystrophy, see FECD1 (136800).
Syndrome with the association of intellectual deficit, truncal obesity, retinal dystrophy and micropenis. It has been described in 14 individuals from a consanguineous family. It is transmitted in an autosomal recessive manner. The causative locus has been mapped to chromosome region 9q34.
An autosomal recessive disorder caused by mutations in the MARVELD2 gene, encoding MARVEL domain-containing protein 2. The condition is characterized by profound prelingual deafness.
Leber congenital amaurosis is a severe retinal dystrophy, causing blindness or severe visual impairment at birth or during the first months of life (summary by den Hollander et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000).
The electrocardiographic (ECG) QT interval, a measure of cardiac repolarization, is a genetically influenced quantitative trait with estimated heritability of approximately 30% (Arking et al., 2006). Very long or short QT intervals occur in a heterogeneous collection of mendelian disorders, the various forms of long QT syndrome (LQTS; see 192500) and short QT syndrome (SQTS; see 609620). These are usually due to rare, highly penetrant mutations in ion channel genes that are associated with increased risk of sudden cardiac death (SCD; see 115080). Familial clustering of SCD has been observed, but the vast majority of subjects who are at risk for SCD do not have mutations in the known genes for LQTS or SQTS.
A rare autosomal dominant form of heart-hand syndrome, first described in members of a Slovenian family. The syndrome has characteristics of adult onset, progressive cardiac conduction disease, tachyarrhythmias that can lead to sudden death, dilated cardiomyopathy and brachydactyly, with the hands less severely affected than the feet. Muscle weakness and/or myopathic electromyographic findings have been observed in some cases.
7q11.23 duplication syndrome is characterized by distinctive facial features; cardiovascular disease (dilation of the ascending aorta in 46%); neurologic abnormalities (hypotonia, adventitious movements, and abnormal gait and station); speech sound disorders including motor speech disorders (childhood apraxia of speech and/or dysarthria) and phonologic disorders; behavior problems including anxiety disorders (especially social anxiety disorder [social phobia]), selective mutism, attention deficit hyperactivity disorder (ADHD), oppositional disorders, physical aggression, and autism spectrum disorders (ASD); delayed motor, speech, and social skills in early childhood; and intellectual ability ranging from intellectual disability (~18%) to borderline intellectual ability (~20%) to low average to high average (the remainder). Approximately 30% of individuals with the 7q11.23 duplication have one or more congenital anomalies.
Mutations in the CRYBB3 gene have been identified in families with cataract, described as congenital nuclear cataract with cortical riders, nuclear, posterior polar, anterior polar, and cortical. The preferred title/symbol of this entry was formerly 'Cataract, Congenital Nuclear, Autosomal Recessive 2; CATCN2.'
Proopiomelanocortin (POMC) deficiency is characterized by severe, early-onset hyperphagic obesity and congenital adrenal insufficiency, the latter secondary to corticotropin (ACTH) deficiency. In the first months of life most children with POMC deficiency experience exponential weight gain, hyperphagia, cholestasis, and adrenal insufficiency. Weight gain continues rapidly, so that by the end of the first year of life obesity is severe (i.e., weight well above the 98th centile for age, without increased height). Red hair and Fitzpatrick type 1 skin (which always burns and never tans) are common, but not invariably present. On occasion central hypothyroidism (resulting from thyroid stimulating hormone [TSH] deficiency), adolescent-onset growth hormone (GH) deficiency, and adolescent-onset hypogonadotropic hypogonadism resulting from deficiency of luteinizing hormone (LH) and follicule stimulating hormone (FSH) can be observed.
Brooke-Spiegler syndrome is an autosomal dominant disorder classically characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life (Scheinfeld et al., 2003). Because BRSS, familial cylindromatosis, and MFT1 are allelic, and because different manifestations of each have been described within a single family, many consider these disorders to represent a phenotypic spectrum of a single disease entity (Gerretsen et al., 1995; Lee et al., 2005; Bowen et al., 2005; Young et al., 2006; Saggar et al., 2008). Blake and Toro (2009) provided a review of Brooke-Spiegler syndrome and pathogenic mutations in the CYLD gene.
Vertical bony ridge positioned in the midline of the forehead.
The presence of unusually deep creases (ridges/wrinkles) on the skin of sole of foot.
Hypobetalipoproteinemia (HBL) is defined as permanently low levels, below the 5th percentile of sex- and age-matched individuals in the population, of apolipoprotein B (apoB), total cholesterol, and low-density lipoprotein (LDL) cholesterol; the lipid profile in FHBL2 includes low HDL cholesterol as well. HBL can result from environmental factors such as a strict vegetarian diet, or can be secondary to certain diseases such as intestinal fat malabsorption, chronic pancreatitis, severe liver disease, malnutrition, or hyperthyroidism. Heritable primary causes of HBL include chylomicron retention disease (CMRD; 246700), abetalipoproteinemia (200100), and familial hypobetalipoproteinemia (FHBL) (summary by Martin-Campos et al., 2012). For a discussion of genetic heterogeneity of familial hypobetalipoproteinemia, see FHBL1 (615558).
Microhydranencephaly (MHAC) is a severe neurodevelopmental defect characterized by extreme microcephaly, profound motor and mental retardation, spasticity, and incomplete cerebral formation. Radiologic studies show gross dilation of the ventricles resulting from the absence of cerebral hemispheres or severe delay in their development, as well as hypoplasia of the corpus callosum, cerebellum, and brainstem (summary by Guven et al., 2012).
Reduced ability to move the vertebral column with a resulting limitation of neck and trunk flexion.
Wolfram syndrome-2 is an autosomal recessive neurodegenerative disorder characterized by diabetes mellitus, high frequency sensorineural hearing loss, optic atrophy or neuropathy, and defective platelet aggregation resulting in peptic ulcer bleeding (summary by Mozzillo et al., 2014). For a discussion of genetic heterogeneity of Wolfram syndrome, see WFS1 (222300).
Lack of symmetry between the left and right halves of the thorax.
Okamoto syndrome is characterised by congenital hydronephrosis, intellectual deficit, growth retardation, cleft palate, generalised hypotonia and a characteristic face. Cardiac anomalies have also been reported. To date, 6 cases have been reported.
North American Indian childhood cirrhosis is a rare liver disorder that occurs in children. The liver malfunction causes yellowing of the skin and whites of the eyes (jaundice) in affected infants. The disorder worsens with age, progressively damaging the liver and leading to chronic, irreversible liver disease (cirrhosis) in childhood or adolescence. Unless it is treated with liver transplantation, North American Indian childhood cirrhosis typically causes life-threatening complications including liver failure.
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
The middle finger is more than 2 SD above the mean for newborns 27 to 41 weeks EGA or above the 97th centile for children from birth to 16 years of age AND the five digits retain their normal length proportions relative to each other (i.e., it is not the case that the middle finger is the only lengthened digit), or, Fingers that appear disproportionately long compared to the palm of the hand.
Spastic paraplegia-12 is an autosomal dominant neurodegenerative disorder characterized by lower limb spasticity and hyperreflexia, resulting in walking difficulties. Some patients may have urinary symptoms and distal sensory impairment. The age at onset is variable and can range from childhood to adulthood (summary by Montenegro et al., 2012). For a general description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
As its name suggests, a Huntington disease-like (HDL) syndrome is a condition that resembles Huntington disease. Researchers have described four HDL syndromes, designated Huntington disease-like 1 (HDL1) through Huntington disease-like 4 (HDL4). These progressive brain disorders are characterized by uncontrolled movements, emotional problems, and loss of thinking ability. HDL syndromes occur in people with the characteristic features of Huntington disease who do not have a mutation in HD, the gene typically associated with that disorder.HDL1, HDL2, and HDL4 usually appear in early to mid-adulthood, although they can begin earlier in life. The first signs and symptoms of these conditions often include irritability, emotional problems, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many affected people develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these abnormal movements become more pronounced. Affected individuals may develop problems with walking, speaking, and swallowing. People with these disorders also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with an HDL syndrome can live for a few years to more than a decade after signs and symptoms begin.HDL3 begins much earlier in life than most of the other HDL syndromes (usually around age 3 or 4). Affected children experience a decline in thinking ability, difficulties with movement and speech, and seizures. Because HDL3 has a somewhat different pattern of signs and symptoms and a different pattern of inheritance, researchers are unsure whether it belongs in the same category as the other HDL syndromes.
Generalized muscular hypotonia (abnormally low muscle tone).
Weakness of the limb-girdle muscles (also known as the pelvic and shoulder girdles), that is, lack of strength of the muscles around the shoulders and the pelvis.
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a general phenotypic description and discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).
Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).
Bare lymphocyte syndrome type I (BLS I) is an inherited disorder of the immune system (primary immunodeficiency). Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria or viruses. Starting in childhood, most people with BLS I develop recurrent bacterial infections in the lungs and airways (respiratory tract). These recurrent infections can lead to a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems.Many people with BLS I also have open sores (ulcers) on their skin, usually on the face, arms, and legs. These ulcers typically develop in adolescence or young adulthood. Some people with BLS I have no symptoms of the condition.People with BLS I have a shortage of specialized immune proteins called major histocompatibility complex (MHC) class I proteins on cells, including infection-fighting white blood cells (lymphocytes), which is where the condition got its name.
Autosomal recessive Charcot-Marie-Tooth disease type 4B is a demyelinating hereditary motor and sensory neuropathy characterized by abnormal folding of myelin sheaths. CMT4B1 (601382) is a clinically similar disorder caused by mutation in the MTMR2 gene (603557) on 11q22. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating CMT, see CMT4A (214400).
A loss of myelinated nerve fibers in the peripheral nervous system (in general, this finding can be observed on nerve biopsy).
A suprabasal subtype of epidermolysis bullosa simplex characterised by generalised superficial erosions and less commonly blistering. Prevalence is unknown but 11 cases have been reported to date. Onset of the disease is usually at birth with skin blistering and generalised erythema which rapidly regresses. The disease is due to mutations in the PKP1 (1q32) gene encoding plakophilin-1. Transmission is autosomal recessive.
Familial combined hyperlipidemia is a common familial lipid disorder characterized by a variable pattern of elevated levels of plasma cholesterol and/or triglycerides. It is present in 10 to 20% of patients with premature coronary artery disease.
HMSNO is an autosomal dominant neurodegenerative disorder characterized by young adult onset of proximal or distal muscle weakness and atrophy, muscle cramps, and fasciculations, with later onset of distal sensory impairment. The disorder is slowly progressive and clinically resembles amyotrophic lateral sclerosis (ALS; 105400) (summary by Ishiura et al., 2012).
Spinocerebellar ataxia type 11 (SCA11) is characterized by progressive cerebellar ataxia and abnormal eye signs (jerky pursuit, horizontal and vertical nystagmus). Pyramidal features, peripheral neuropathy, and dystonia are seen on occasion. Four families have been reported to date: one each from the UK, France, Germany, and Pakistan. In them, age of onset ranged from the early teens to the mid 20s. Life span is normal.
A rare pleiotropic auto-inflammatory disorder of childhood, primarily affecting the joints and skin. The first affected family contained ten affected members from three generations and manifested variable expression of a pauciarticular, nonaxial, arthritis that began in childhood; pyoderma gangrenosum; and severe cystic acne in adolescence and beyond. Recurrent sterile arthritis usually occurs after minor trauma, but can also occur spontaneously. PAPA syndrome is a self-limiting disease, but it can lead to severe joint destruction. The gene responsible for the syndrome is the proline-serine-threonine phosphatase interacting protein 1 (PSTPIP1).
Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (LCA), whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). Various intermediate phenotypes between LCA and retinitis pigmentosa are known and are sometimes described as 'early-onset severe rod-cone dystrophy' or 'early-onset retinal degeneration' (Booij et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000; for cone-rod dystrophy, see 120970.
The presence of renal tubules with thick redundant basement membranes, or a reduction of greater than 50% in tubular diameter compared to surrounding non-atrophic tubules.
Cardioencephalomyopathy due to cytochrome c oxidase deficiency is an autosomal recessive mitochondrial disorder characterized by onset of cardiomyopathy either in utero or in the first days of life. Most patients also show neurologic abnormalities, such as abnormal breathing pattern, nystagmus, and gyral abnormalities, consistent with encephalopathy. The disorder is usually fatal in early infancy (summary by Papadopoulou et al., 1999). Genetic Heterogeneity of Fatal Infantile Cardioencephalomyopathy Due to Cytochrome c Oxidase Deficiency See also CEMCOX2 (615119), caused by mutation in the COX15 gene (603646) on chromosome 10q24; CEMCOX3 (616500), caused by mutation in the COA5 gene (613920) on chromosome 2q11; and CEMCOX4 (616501), caused by mutation in the COA6 gene (614772) on chromosome 1q42. For a phenotypic description and a discussion of genetic heterogeneity of cytochrome c oxidase deficiency, see 220110.
Death within the first 24 months of life. [HPO:probinson]
The presence of an abnormally thick calvaria.
A designation that has some relationship to motherhood.
A rare genetic epilepsy disorder with characteristics of autosomal dominant lesional and nonlesional focal epilepsy with variable penetrance. Focal seizures emanate from different cortical locations (temporal, frontal, centroparietal, parietal, parietal-occipital, occipital) in different family members, but for each individual a single focus remains constant throughout lifetime. Seizure type (tonic, tonic-clonic or hyperkinetic) and severity varies among family members and tends to decrease (but do not disappear) during adulthood. Many patients have an aura and show automatisms during diurnal seizures whereas others have nocturnal seizures. Most individuals are of normal intelligence but patients with intellectual disability, autistic spectrum disorder and obsessive-compulsive disorder have been described.
Spastic paraplegia 11 (SPG11) is characterized by progressive spasticity and weakness of the lower limbs frequently associated with the following: mild intellectual disability with learning difficulties in childhood and/or progressive cognitive decline; peripheral neuropathy; pseudobulbar involvement; and increased reflexes in the upper limbs. Less frequent findings include: cerebellar signs (ataxia, nystagmus, saccadic pursuit); retinal degeneration; pes cavus; scoliosis; and parkinsonism. Onset occurs mainly during infancy or adolescence (range: age 1-31 years). Most affected individuals become wheelchair bound one or two decades after disease onset.
A very rare circadian rhythm sleep disorder with main features of very early sleep onset and offset possibly resulting in emotional and physical disruptions.
Primary microcephaly (MCPH) is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean and mental retardation, with no other associated malformations and with no apparent etiology. Most cases of primary microcephaly show an autosomal recessive mode of inheritance (summary by Woods et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an inherited condition that causes muscle weakness and respiratory failure typically beginning in infancy. Early features of this condition are difficult and noisy breathing, especially when inhaling; a weak cry; problems feeding; and recurrent episodes of pneumonia. Typically between the ages of 6 weeks and 6 months, infants with this condition will experience a sudden inability to breathe due to paralysis of the muscle that separates the abdomen from the chest cavity (the diaphragm). Normally, the diaphragm contracts and moves downward during inhalation to allow the lungs to expand. With diaphragm paralysis, affected individuals require life-long support with a machine to help them breathe (mechanical ventilation). Rarely, children with SMARD1 develop signs or symptoms of the disorder later in childhood.Soon after respiratory failure occurs, individuals with SMARD1 develop muscle weakness in their distal muscles. These are the muscles farther from the center of the body, such as muscles in the hands and feet. The weakness soon spreads to all muscles; however, within 2 years, the muscle weakness typically stops getting worse. Some individuals may retain a low level of muscle function, while others lose all ability to move their muscles. Muscle weakness severely impairs motor development, such as sitting, standing, and walking. Some affected children develop an abnormal side-to-side and back-to-front curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). After approximately the first year of life, individuals with SMARD1 may lose their deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer.Other features of SMARD1 can include reduced pain sensitivity, excessive sweating (hyperhidrosis), loss of bladder and bowel control, and an irregular heartbeat (arrhythmia).
Interruption of the innervation of the diaphragm.
Microcephaly-2 with or without cortical malformations is an autosomal recessive neurodevelopmental disorder showing phenotypic variability. Classically, primary microcephaly is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations (SD) below the age- and sex-matched population mean, and mental retardation with no other associated malformations and with no apparent etiology (Hofman, 1984). Patients with WDR62 mutations have head circumferences ranging from low-normal to severe (-9.8 SD), and most patients with brain scans have shown various types of cortical malformations. All have delayed psychomotor development; seizures are variable (summary by Yu et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Superior margin of the scrotum superior to the base of the penis.
Hemangioma, a benign tumor of the vascular endothelial cells with small endothelial spaces, occurring in the face.
Juvenile idiopathic arthritis refers to a group of conditions involving joint inflammation (arthritis) that first appears before the age of 16. This condition is an autoimmune disorder, which means that the immune system malfunctions and attacks the body's organs and tissues, in this case the joints.Researchers have described seven types of juvenile idiopathic arthritis. The types are distinguished by their signs and symptoms, the number of joints affected, the results of laboratory tests, and the family history.Systemic juvenile idiopathic arthritis causes inflammation in one or more joints. A high daily fever that lasts at least 2 weeks either precedes or accompanies the arthritis. Individuals with systemic arthritis may also have a skin rash or enlargement of the lymph nodes (lymphadenopathy), liver (hepatomegaly), or spleen (splenomegaly).Oligoarticular juvenile idiopathic arthritis (also known as oligoarthritis) has no features other than joint inflammation. Oligoarthritis is marked by the occurrence of arthritis in four or fewer joints in the first 6 months of the disease. It is divided into two subtypes depending on the course of disease. If the arthritis is confined to four or fewer joints after 6 months, then the condition is classified as persistent oligoarthritis. If more than four joints are affected after 6 months, this condition is classified as extended oligoarthritis.Rheumatoid factor positive polyarticular juvenile idiopathic arthritis (also known as polyarthritis, rheumatoid factor positive) causes inflammation in five or more joints within the first 6 months of the disease. Individuals with this condition also have a positive blood test for proteins called rheumatoid factors. This type of arthritis closely resembles rheumatoid arthritis as seen in adults.Rheumatoid factor negative polyarticular juvenile idiopathic arthritis (also known as polyarthritis, rheumatoid factor negative) is also characterized by arthritis in five or more joints within the first 6 months of the disease. Individuals with this type, however, test negative for rheumatoid factor in the blood.Psoriatic juvenile idiopathic arthritis involves arthritis that usually occurs in combination with a skin disorder called psoriasis. Psoriasis is a condition characterized by patches of red, irritated skin that are often covered by flaky white scales. Some affected individuals develop psoriasis before arthritis while others first develop arthritis. Other features of psoriatic arthritis include abnormalities of the fingers and nails or eye problems.Enthesitis-related juvenile idiopathic arthritis is characterized by tenderness where the bone meets a tendon, ligament or other connective tissue. This tenderness, known as enthesitis, accompanies the joint inflammation of arthritis. Enthesitis-related arthritis may also involve inflammation in parts of the body other than the joints.The last type of juvenile idiopathic arthritis is called undifferentiated arthritis. This classification is given to affected individuals who do not fit into any of the above types or who fulfill the criteria for more than one type of juvenile idiopathic arthritis.
A duplication of the collecting system of the kidney, defined as a kidney with two (instead of, normally, one) pyelocaliceal systems. The pyelocaliceal system is comprised of the renal pelvis and calices. The duplicated renal collecting system can be associated with a single ureter or with double ureters. In the latter case, the two ureters empty separately into the bladder or fuse to form a single ureteral orifice.
An abnormality of the lacrimal duct, a duct that drain tears from the conjunctiva, via the lacrimal puncta, into the lacrimal sac.
A human skin color characterized by low levels of eumelanin.
Reduced number or density of pubic hair.
Reduced number or density of axillary hair.
More than a quarter of the human population is affected by soil-transmitted helminthes, which impair nutrition and the immune response to widespread pandemics, such as acquired immunodeficiency syndrome (see 609423) and tuberculosis (see 607948). The roundworm Ascaris lumbricoides, the most common human parasite of the gastrointestinal tract, causes ascariasis, which has a worldwide distribution with highest prevalence in tropical and subtropical regions and in areas with inadequate sanitation. Ascariasis is triggered by ingestion of parasite eggs. During its life cycle, Ascaris threatens human health with nonspecific abdominal symptoms, intestinal obstruction and perforation, biliary colic, gallstone formation, liver abscesses, pancreatitis, and pulmonary eosinophilia (Sanglas et al., 2009).
Anemia not associated with symptoms of fatigue, headaches, palpitations, or shortness of breath. In asymptomatic anemia the hematocrit levels usually range from 32 to 35%.
A rare non-hereditary condition characterised by gastrointestinal stromal tumours (GIST), pulmonary chondromas and extraadrenal paragangliomas. Less than 100 cases have been reported worldwide. The disease primarily affects young women (mean age of onset 20 years). Most patients initially present with two of the three tumours (incomplete Carney's triad). The main symptoms at presentation are gastrointestinal bleeding, epigastric pain, anaemia and palpable abdominal mass. These symptoms are related to the GIST, which occur in 99% of cases. Pulmonary chondromas occur in approximately 80% of cases. Secreting paragangliomas (typically extraadrenal and most often mediastinal) occur in approximately 50% of patients. The aetiology is not completely understood. Impaired succinate dehydrogenase (SDH) function resulting from chromosomal losses (but not mutations) has been detected in some patients with Carney's triad.
TFR2-related hereditary hemochromatosis (TFR2-HHC) is characterized by increased intestinal iron absorption resulting in iron accumulation in the liver, heart, pancreas, and endocrine organs. Age of onset is earlier than in HFE-associated HHC. The majority of individuals present with signs and symptoms of iron overload in the third decade (e.g., weakness, fatigue, abdominal pain, hepatomegaly, arthritis, arthralgia, progressive increase in skin pigmentation). Others present as young adults with nonspecific symptoms and abnormal serum iron studies or as adults with abnormal serum iron studies and signs of organ involvement including cirrhosis, diabetes mellitus, and arthropathy.
SCN1A seizure disorders encompass a spectrum that ranges from simple febrile seizures and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end. Phenotypes with intractable seizures including Dravet syndrome are often associated with cognitive decline. Less commonly observed phenotypes include myoclonic astatic epilepsy (MAE), Lennox-Gastaut syndrome, infantile spasms, epilepsy with focal seizures, and vaccine-related encephalopathy and seizures. The phenotype of SCN1A seizure disorders can vary even within the same family.
Mutations in the GABRG2 gene cause a spectrum of seizure disorders, ranging from early-onset isolated febrile seizures to generalized epilepsy with febrile seizures plus, type 3, which represents a more severe phenotype. Patients with isolated febrile seizures usually have onset in the first year of life and show spontaneous remission by age 6 years, whereas patients with GEFS+ continue to have various types of febrile and afebrile seizures later in life (summary by Singh et al., 1999). Mutation in the GABRG2 gene can also cause childhood absence epilepsy (ECA2; 607681). Mutations in certain genes can cause a phenotypic spectrum of overlap between the isolated febrile phenotype and the GEFS+ phenotype. For a general phenotypic description and a discussion of genetic heterogeneity of GEFS+, see 604233. For a phenotypic description and a discussion of genetic heterogeneity of familial febrile seizures, see 121210.
Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis, whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). Mackay et al. (2011) concluded that SPATA7 retinopathy is an infantile-onset severe cone-rod dystrophy with early extensive peripheral retinal atrophy but with variable foveal involvement. For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000.
Mutations in the CRYAA gene have been found to cause multiple types of cataract, which have been described as nuclear, zonular central nuclear, laminar, lamellar, anterior polar, posterior polar, cortical, embryonal, anterior subcapsular, fan-shaped, and total. Cataract associated with microcornea, sometimes called the cataract-microcornea syndrome, is also caused by mutation in the CRYAA gene. Both autosomal dominant and autosomal recessive modes of inheritance have been reported. The symbol CATC1 was formerly used for the autosomal recessive form of cataract caused by mutation in the CRYAA gene.
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a disorder that causes progressive dysfunction of the brain (encephalopathy). It is characterized by a loss of intellectual functioning (dementia) and seizures. At first, affected individuals may have difficulty sustaining attention and concentrating. They may experience repetitive thoughts, speech, or movements. As the condition progresses, their personality changes and judgment, insight, and memory become impaired. Affected people lose the ability to perform the activities of daily living, and most eventually require comprehensive care.The signs and symptoms of FENIB vary in their severity and age of onset. In severe cases, the condition causes seizures and episodes of sudden, involuntary muscle jerking or twitching (myoclonus) in addition to dementia. These signs can appear as early as a person's teens. Less severe cases are characterized by a progressive decline in intellectual functioning beginning in a person's forties or fifties.
Chudley-McCullough syndrome is an autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal (summary by Alrashdi et al., 2011).
Hepatointestinal schistosomiasis is caused by 2 species of helminths: Schistosoma japonicum, which is prevalent in Asia, and S. mansoni, which is prevalent in Africa and South America. Both worms develop in the host mesenteric system and lay eggs that trigger inflammation in the hepatic periportal space in which they are trapped. Worms live for years, and chronic liver inflammation and significant tissue destruction are therefore common in infected individuals. Tissue repair begins with deposition of extracellular matrix proteins (ECMPs) in the damaged tissues, which are later replaced by normal hepatocytes. In some individuals, ECMPs accumulate in the periportal space, forming fibrosis deposits that reduce blood flow and cause varicose veins. These individuals may die from the subsequent effects of hepatic fibrosis. About 5 to 10% of the 350 million infected individuals develop severe hepatic fibrosis. Development of hepatic fibrosis in schistosome-infected individuals is influenced by a locus on chromosome 6q23, designated SM2, which contains 2 major candidate genes: IFNGR1 (107470), which encodes a chain of the receptor for interferon-gamma (IFNG; 147570), and CTGF (121009), which encodes a profibrogenic molecule produced by hepatocytes (summary by Dessein et al., 2009).
Spastic paraplegia-10 is an autosomal dominant neurologic disorder with variable manifestations. Some patients have onset of a 'pure' spastic paraplegia, with lower limb spasticity, hyperreflexia, extensor plantar responses, and variable involvement of the upper limbs beginning in childhood or young adulthood. Some patients show distal sensory impairment, which can be part of the 'pure' phenotype. However, some patients also show an axonal sensorimotor peripheral neuropathy with distal sensory impairment and distal muscle atrophy reminiscent of Charcot-Marie-Tooth disease type 2 (see, e.g., CMT2A, 118210). Rarely, patients with KIF5A mutations may have additional neurologic features, including parkinsonism or cognitive decline, consistent with a 'complicated' phenotype. Spastic paraplegia and peripheral neuropathy in isolation may represent extreme ends of the phenotypic spectrum of KIF5A mutations (summary by Goizet et al., 2009 and Crimella et al., 2012).
Poikiloderma with neutropenia (PN) is characterized by an inflammatory eczematous rash (ages 6-12 months) followed by post-inflammatory poikiloderma (age >2 years) and chronic noncyclic neutropenia typically associated with recurrent sinopulmonary infections in the first two years of life and (often) bronchiectasis. There is increased risk for myelodysplastic syndrome and, rarely, acute myelogenous leukemia. Other ectodermal findings include nail dystrophy and palmar/plantar hyperkeratosis. Most affected individuals also have reactive airway disease and some have short stature, hypogonadotropic hypogonadism, midfacial retrusion, calcinosis cutis, and non-healing skin ulcers.
Left ventricular noncompaction (LVNC) is characterized by numerous prominent trabeculations and deep intertrabecular recesses in hypertrophied and hypokinetic segments of the left ventricle (Sasse-Klaassen et al., 2004). The mechanistic basis is thought to be an intrauterine arrest of myocardial development with lack of compaction of the loose myocardial meshwork. LVNC may occur in isolation or in association with congenital heart disease. Distinctive morphologic features can be recognized on 2-dimensional echocardiography (Kurosaki et al., 1999). Noncompaction of the ventricular myocardium is sometimes referred to as spongy myocardium. Stollberger et al. (2002) commented that the term 'isolated LVNC,' meaning LVNC without coexisting cardiac abnormalities, is misleading, because additional cardiac abnormalities are found in nearly all patients with LVNC. Genetic Heterogeneity of Left Ventricular Noncompaction A locus for autosomal dominant left ventricular noncompaction has been identified on chromosome 11p15 (LVNC2; 609470). LVNC3 (see 605906) is caused by mutation in the LDB3 gene (605906) on chromosome 10q23. LVNC4 (see 613424) is caused by mutation in the ACTC1 gene (102540) on chromosome 15q14. LVNC5 (see 613426) is caused by mutation in the MYH7 gene (160760) on chromosome 14q12. LVNC6 (see 601494) is caused by mutation in the TNNT2 gene (191045) on chromosome 1q32. LVNC7 (615092) is caused by mutation in the MIB1 gene (608677) on chromosome 18q11. LVNC8 (615373) is caused by mutation in the PRDM16 gene (605557) on chromosome 1p36. LVNC9 (see 611878) is caused by mutation in the TPM1 gene (191010) on chromosome 15q22. LVNC10 (615396) is caused by mutation in the MYBPC3 gene (600958) on chromosome 11p11. LVNC can also occur as part of an X-linked disorder, Barth syndrome (302060), caused by mutation in the TAZ gene (300394) on chromosome Xq28.
Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) is characterized by abnormalities of the eye (bilateral congenital cataracts, microcornea, microphthalmia, micropupils); mildly dysmorphic facial features apparent in late childhood; and a hypo/demyelinating, symmetric, distal peripheral neuropathy. The neuropathy is predominantly motor at the onset and results in delays in early motor development, progressing to severe disability by the third decade. Secondary scoliosis and foot deformities are common. Sensory neuropathy develops after age ten years. Most affected individuals have a mild non-progressive intellectual deficit and cerebellar involvement including ataxia, nystagmus, intention tremor, and dysmetria. All have short stature and subnormal weight. Adults have hypogonadotropic hypogonadism. Parainfectious rhabdomyolysis (profound muscle weakness, myoglobinuria, and excessively elevated serum concentration of creatine kinase usually following a viral infection) is a potentially life-threatening complication. To date all affected individuals and carriers identified have been from the Roma/Gypsy population.
A type of decreased nerve conduction velocity that affects the motor neuron.
Prominence of the malar process of the maxilla and infraorbital area appreciated in profile and from in front of the face.
The classic phenotype of megalencephalic leukoencephalopathy with subcortical cysts (MLC) is characterized by early-onset macrocephaly, often in combination with mild gross motor developmental delay and seizures; gradual onset of ataxia, spasticity, and sometimes extrapyramidal findings; and usually late onset of mild mental deterioration. Macrocephaly, observed in virtually all individuals, may be present at birth but more frequently develops during the first year of life. The degree of macrocephaly is variable and can be as great as 4 to 6 SD above the mean in some individuals. After the first year of life, head growth rate normalizes and growth follows a line parallel to and usually several centimeters above the 98th centile. Initial mental and motor development is normal in most individuals. Walking is often unstable, followed by ataxia of the trunk and extremities, then minor signs of pyramidal dysfunction and brisk deep-tendon stretch reflexes. Almost all individuals have epilepsy from an early age. The epilepsy is typically well controlled with medication, but status epilepticus occurs relatively frequently. Mental deterioration is late and mild. Disease severity ranges from independent walking for a few years only to independent walking in the fifth decade. Some individuals have died in their teens or twenties; others are alive in their fifties. An improving phenotype has a similar initial presentation with delayed mental or motor development, followed by an improving clinical course: macrocephaly usually persists, but some children become normocephalic; motor function improves or normalizes; hypotonia and clumsiness may persist in some or neurologic examination may become normal. Some have intellectual disability that is stable, with or without autism. Epilepsy and status epilepticus may occur.
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (review by Meyrier, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome (NPHS), see FSGS1 (603278).
A reduction in the rate of apoptosis in lymphocytes.
A chronic form of lymphadenopathy that is not related to infection.
An abnormal increase from the normal count of B cells.
An abnormally increased proportion of CD4-negative, CD8-negative (double negative or DN) alpha-beta regulatory T cells (Tregs) as compared to total number of T cells.
An elevated proportion of T cells that express human leukocyte antigen (HLA)-DR. HLA-DR is an MHC class II cell surface receptor that presents antigens (peptides of at least 9 amino acids), thereby constituting a ligand for the T-cell receptor. HLA-DR can be upregulated in response to immune stimulation.
An abnormally increased level of immunoglobulin G in blood.
Beta thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red blood cells that carries oxygen to cells throughout the body.In people with beta thalassemia, low levels of hemoglobin lead to a lack of oxygen in many parts of the body. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. People with beta thalassemia are at an increased risk of developing abnormal blood clots.Beta thalassemia is classified into two types depending on the severity of symptoms: thalassemia major (also known as Cooley's anemia) and thalassemia intermedia. Of the two types, thalassemia major is more severe.The signs and symptoms of thalassemia major appear within the first 2 years of life. Children develop life-threatening anemia. They do not gain weight and grow at the expected rate (failure to thrive) and may develop yellowing of the skin and whites of the eyes (jaundice). Affected individuals may have an enlarged spleen, liver, and heart, and their bones may be misshapen. Some adolescents with thalassemia major experience delayed puberty. Many people with thalassemia major have such severe symptoms that they need frequent blood transfusions to replenish their red blood cell supply. Over time, an influx of iron-containing hemoglobin from chronic blood transfusions can lead to a buildup of iron in the body, resulting in liver, heart, and hormone problems.Thalassemia intermedia is milder than thalassemia major. The signs and symptoms of thalassemia intermedia appear in early childhood or later in life. Affected individuals have mild to moderate anemia and may also have slow growth and bone abnormalities.
Childhood ataxia with central nervous system hypomyelination / vanishing white matter (CACH/VWM) is characterized by ataxia, spasticity, and variable optic atrophy. The phenotypic range includes a prenatal/congenital form, a subacute infantile form (onset age <1 year), an early childhood-onset form (onset age 1 to <4 years), a late childhood-/juvenile-onset form (onset age 4 to <18 years), and an adult-onset form (onset =18 years). The prenatal/congenital form is characterized by severe encephalopathy. In the later-onset forms initial motor and intellectual development is normal or mildly delayed, followed by neurologic deterioration with a chronic progressive or subacute course. While in childhood-onset forms motor deterioration dominates, in adult-onset forms cognitive decline and personality changes dominate. Chronic progressive decline can be exacerbated by rapid deterioration during febrile illnesses or following head trauma or major surgical procedures, or by acute and extreme fright.
An reduced concentration of progesterone in the blood.
A rare congenital disorder in which congenital central hypoventilation syndrome occurs concurrently with Hirschsprung disease. Intestinal aganglionosis is more extensive, and the gender ratio is 1:1, unlike in classical Hirschsprung disease. Mutations in the PHOX2B gene are found in a significant number of patients with Haddad syndrome.
Long QT syndrome (LQTS) is a cardiac electrophysiologic disorder, characterized by QT prolongation and T-wave abnormalities on the ECG that are associated with tachyarrhythmias, typically the ventricular tachycardia torsade de pointes (TdP). TdP is usually self-terminating, thus causing a syncopal event, the most common symptom in individuals with LQTS. Such cardiac events typically occur during exercise and emotional stress, less frequently during sleep, and usually without warning. In some instances, TdP degenerates to ventricular fibrillation and causes aborted cardiac arrest (if the individual is defibrillated) or sudden death. Approximately 50% of untreated individuals with a pathogenic variant in one of the genes associated with LQTS have symptoms, usually one to a few syncopal events. While cardiac events may occur from infancy through middle age, they are most common from the preteen years through the 20s. Some types of LQTS are associated with a phenotype extending beyond cardiac arrhythmia. In addition to the prolonged QT interval, associations include muscle weakness and facial dysmorphism in Andersen-Tawil syndrome (LQTS type 7), hand/foot, facial, and neurodevelopmental features in Timothy syndrome (LQTS type 8), and profound sensorineural hearing loss in Jervell and Lange-Nielson syndrome.
Aplasia or developmental hypoplasia of the nail.
A multiple congenital anomalies/dysmorphic syndrome with characteristics of multiple skeletal malformations (short femora and humeri, bilateral absence of metatarsal and metacarpal bone in hands and feet, bilateral partial syndactyly of fingers and toes or oligo/polysyndactyly, deformed lumbosacral spine), congenital heart disease (truncus arteriosus), lung and urogenital malformations (bilateral bilobar lungs, horseshoe kidney, cryptorchidism), and facial malformations (bilateral cleft lip and palate, micrognathia, small, low-set ears without external meatus). It is lethal in the neonatal period. There have been no further descriptions in the literature since 1981.
This syndrome has characteristics of intellectual deficit, calcification of the choroid plexus and elevated levels of cerebrospinal fluid protein. It has been described in two sibships from two unrelated families. The seven children of one of the sibships were born to consanguineous parents. Some patients also had strabismus, hyperactive deep tendon reflexes and foot deformities.
A slow-growing malignant bone tumor arising from the remnants of the notochord and occurring in the spine. It is characterized by a lobulated growth pattern, myxoid stroma formation, and the presence of physaliphorous cells.
Deposition of calcium salts in point-like foci within the anterior portion of one or more ribs.
The presence of abnormal punctate (speckled, dot-like) calcifications in one or more epiphyses.
Rhizomelic chondrodysplasia punctata type 1 (RCDP1) classic type, a peroxisome biogenesis disorder (PBD), is characterized by proximal shortening of the humerus and to a lesser degree the femur (rhizomelia), punctate calcifications in cartilage with epiphyseal and metaphyseal abnormalities (chondrodysplasia punctata, or CDP), coronal clefts of the vertebral bodies, and cataracts that are usually present at birth or appear in the first few months of life. Birth weight, length, and head circumference are often at the lower range of normal; postnatal growth deficiency is profound. Intellectual disability is severe, and the majority of children develop seizures. Most affected children do not survive the first decade of life; a proportion die in the neonatal period. A milder phenotype in which all affected individuals have congenital cataracts and chondrodysplasia is now recognized; some do not have rhizomelia, and some have less severe intellectual disability and growth deficiency.
Blomstrand chondrodysplasia is an autosomal recessive disorder characterized by short limbs, polyhydramnios, hydrops fetalis, facial anomalies, increased bone density, and advanced skeletal maturation (summary by Loshkajian et al., 1997).
Calcification (abnormal deposits of calcium) in the laryngeal tissues.
Griscelli syndrome type 1 (GS1) represents hypomelanosis with a primary neurologic deficit and without immunologic impairment or manifestations of hemophagocytic syndrome (Menasche et al., 2002). Griscelli syndrome with immune impairment, or Griscelli syndrome type 2 (607624), is caused by mutation in the RAB27A gene (603868). Griscelli syndrome type 3 (609227), characterized by hypomelanosis with no immunologic or neurologic manifestations, can be caused by mutation in the melanophilin (MLPH; 606526) or MYO5A genes. Griscelli syndrome is a rare autosomal recessive disorder that results in pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. While most patients also develop hemophagocytic syndrome, leading to death in the absence of bone marrow transplantation (Menasche et al., 2000), some show severe neurologic impairment early in life without apparent immune abnormalities. Bahadoran et al. (2003) characterized GS1 as comprising hypomelanosis and severe central nervous system dysfunction, corresponding to the 'dilute' phenotype in the mouse, and GS2 as comprising hypomelanosis and lymphohistiocytotic hemophagocytosis, corresponding to the 'ashen' phenotype in mouse. Anikster et al. (2002), Menasche et al. (2002), Huizing et al. (2002), and Bahadoran et al. (2003, 2003) suggested that Elejalde syndrome (256710) in some patients and GS1 represent the same entity.
Klippel-Feil syndrome (KFS) is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae, resulting in a fused appearance. The clinical triad consists of short neck, low posterior hairline, and limited neck movement, although less than 50% of patients demonstrate all 3 clinical features (Tracy et al., 2004). Clarke et al. (1998) proposed a classification system for KFS in which an autosomal recessive form is characterized by the most rostral fusion at C1 and the presence of severe associated anomalies, including short neck, cardiac defects, and craniofacial anomalies. For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100).
Narrow, paramedian longitudinal depressions in the plantar skin of the forefoot.
Neonatal jaundice refers to a yellowing of the skin and other tissues of a newborn infant as a result of increased concentrations of bilirubin in the blood. Neonatal jaundice affects over half of all newborns to some extent in the first week of life. Prolonged neonatal jaundice is said to be present if the jaundice persists for longer than 14 days in term infants and 21 days in preterm infants. [HPO:probinson]
Increased concentration of long-chain fatty acid.
Cerebro-facio-thoracic dysplasia is a rare condition characterized by abnormal development (dysplasia) of the brain (cerebro) and structures in the face (facio) and torso (thoracic). The problems with development lead to the key features of cerebro-facio-thoracic dysplasia, which include severe intellectual disability, distinctive facial features, and abnormalities of the ribs and spinal bones (vertebrae).In addition to intellectual disability, individuals with cerebro-facio-thoracic dysplasia have delayed development of speech and movement (motor) skills, and in some, these skills never develop. Nearly one-quarter of affected individuals never learn to speak and almost half are unable to walk. Weak muscle tone (hypotonia) and difficulty feeding occur in some affected infants. People with cerebro-facio-thoracic dysplasia can have behavioral problems, such as anxiety, autism spectrum disorder, or self-injuring behavior; however, many people with the condition are described as friendly and good-natured.Distinctive facial features common in cerebro-facio-thoracic dysplasia include a wide, short skull (brachycephaly); highly arched eyebrows or eyebrows that grow together in the middle (synophrys); widely spaced eyes (hypertelorism); a wide nasal bridge; low-set ears; an upper lip with pronounced curves (Cupid's bow upper lip); and small teeth (microdontia). Some affected individuals have overgrowth of the gums (gingival hyperplasia), an opening in the roof of the mouth (cleft palate), or a split in the upper lip (cleft lip).Problems with bone development in the torso (thorax) commonly leads to bone abnormalities such as two or more ribs that are joined together (fused) or ribs that are abnormally shaped with two prongs at one end (bifid ribs). Many people with cerebro-facio-thoracic dysplasia have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae; some vertebrae may also be fused. Additionally, the shoulder blades can be affected in people with this condition.A wide variety of other features can occur in cerebro-facio-thoracic dysplasia, such as abnormalities involving the eyes, skin, or hair. Heart defects, digestive problems, or genitourinary problems (such as abnormal kidneys or reproductive organs) can also occur. Affected individuals may also have bone or joint abnormalities in other parts of the body.
A facial appearance characterized by a permanently or nearly permanently opened mouth, in which the upper lip is tented in a way that the opened mouth has the appearance of a triangle.
Autosomal recessive spinocerebellar ataxia-2 is an neurologic disorder characterized by onset of impaired motor development and ataxic gait in early childhood. Additional features often include loss of fine motor skills, dysarthria, nystagmus, cerebellar signs, and delayed cognitive development with intellectual disability. Brain imaging shows cerebellar atrophy. Overall, the disorder is non- or slowly progressive, with survival into adulthood (summary by Jobling et al., 2015).
A very rare disease, characterised by hypodontia and sparse hair in combination with cerebellar ataxia and normal intelligence. Imaging demonstrates cerebellar atrophy.
A congenital malformation syndrome that associates a complex syndactyly of the hands with malformations of the forearm bones and similar manifestations in the lower limbs. Fewer than 30 cases have been described, the majority of cases occurred in related families. The syndrome affects both the upper and lower limbs but, in general, the latter are less severely affected. Associated malformations (renal hypoplasia and vertebral and hemi-vertebral anomalies) have occasionally been reported. Mild facial dysmorphism has been described in isolated cases. The disease is transmitted as an autosomal recessive trait. Homozygous or compound heterozygous mutations of the LRP4 gene (11p12-p11.2) have been identified.
Palmoplantar keratoderma and congenital alopecia-2 (PPKCA2) is an autosomal recessive disorder characterized by congenital alopecia and progressive hyperkeratosis resulting in sclerodactyly, severe contractures and tapering of the digits, and pseudoainhum formation. Nail changes occur in some patients (Castori et al., 2010). Also see PPKCA1 (104100), a less severe, autosomal dominant disorder.
Sengers syndrome is an autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy (summary by Mayr et al., 2012). Skeletal muscle biopsies of 2 affected individuals showed severe mtDNA depletion (Calvo et al., 2012).
Heart defects limb shortening is an association disorder combining congenital heart malformation and skeletal dysplasia (including coronal clefting of the vertebral bodies and short limbs). It has been described only once in the literature, in two male siblings from Kuwaiti first cousins. The clinical and radiological features of these patients were reported as a distinct cardio-skeletal syndrome.
Hypoplasia of the cerebellum, pontine nuclei, and inferior olivary nucleus.
A rare syndrome with characteristics of camptodactyly, muscle hypoplasia and weakness, skeletal anomalies, facial dysmorphism and abnormal dermatoglyphics. Dysmorphic features include facial asymmetry, hypertelorism, broad nasal bridge, long philtrum and a small mouth. Winging scapulae, scoliosis, syndactyly and clinodactyly are commonly observed. The affected patients usually have normal mental development. The molecular basis of the syndrome has not yet been elucidated.
A rare syndrome consisting of growth retardation, facial dysmorphism, camptodactyly and skeletal anomalies. To date only eight cases have been reported in the literature. Dysmorphic features include flat face, epicanthic folds, telecanthus, small downturned mouth, small ears with attached lobule and abnormal dental eruption and occlusion. Some patients had psychomotor development delayed. The reported cases suggest the condition is hereditary and is transmitted as an autosomal recessive trait.
An abnormality of tooth eruption. [HPO:ibailleulforestier]
The distal interphalangeal joint and/or the proximal interphalangeal joint of the second to fifth fingers cannot be extended to 180 degrees by either active or passive extension.
The association of limb defects and multivisceral anomalies. The syndrome has been reported in eight infants from four different families. Skeletal features include tetramelic campomelia and short long bones. Extraskeletal manifestations may include cervical lymphocele, generalised hydrops, polycystic kidneys, pancreas and liver, fibrotic liver or pancreas, polysplenia, heterotaxia, hypoplastic lung, short bowel. All newborns reported so far were either stillborn or died shortly after birth.
Adult-onset calcification of the lower extremity arteries, including the iliac, femoral, and tibial arteries, and hand and foot capsule joints is an autosomal recessive condition that represents only the second mendelian disorder of isolated calcification (see generalized arterial calcification of infancy (GACI), 208000). Age of onset has been reported as early as the second decade of life, usually involving intense joint pain or calcification in the hands (St. Hilaire et al., 2011).
This syndrome has characteristics of congenital anodontia, a small maxilla, short stature with shortened metacarpals and metatarsals, sparse hair, albinoidism and multiple ocular anomalies. It has been described in three siblings (one brother and two sisters). Transmission is autosomal recessive.
A bending or abnormal curvature of the radius.
Bowen-Conradi syndrome is a disorder that affects many parts of the body and is usually fatal in infancy. Affected individuals have a low birth weight, experience feeding problems, and grow very slowly. Their head is unusually small overall (microcephaly), but is longer than expected compared with its width (dolichocephaly). Characteristic facial features include a prominent, high-bridged nose and an unusually small jaw (micrognathia) and chin. Affected individuals typically have pinky fingers that are curved toward or away from the ring finger (fifth finger clinodactyly) or permanently flexed (camptodactyly), feet with soles that are rounded outward (rocker-bottom feet), and restricted joint movement.Other features that occur in some affected individuals include seizures; structural abnormalities of the kidneys, heart, brain, or other organs; and an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Affected males may have the opening of the urethra on the underside of the penis (hypospadias) or undescended testes (cryptorchidism).Babies with Bowen-Conradi syndrome do not achieve developmental milestones such as smiling or sitting, and they usually do not survive more than 6 months.
A lethal bone dysplasia with characteristics of low birth weight, rhizomelic dwarfism, bent femora and short chest producing asphyxia. The disease has been described in three siblings from healthy, non-consanguineous parents of Finnish origin and in four siblings from non-consanguineous parents of French origin with no family history of dwarfism. There has been no further description of this disease in the literature since 1988.
A type of chromosomal aberration reduced resistance of chromosomes to change or deterioration.
Reduced strength of the frontalis muscle (which is located on the forehead).
A type of dysharmonic skeletal maturation in which there is a delay in skeletal maturation whose degree differs markedly in different bones.
Underdevelopment of the ischium, which forms the lower and back part of the hip bone.
Decreased width of the diaphysis of long bones.
Microcephalic osteodysplastic primordial dwarfism type I is a severe autosomal recessive skeletal dysplasia characterized by dwarfism, microcephaly, and neurologic abnormalities, including mental retardation, brain malformations, and ocular/auditory sensory deficits. Patients often die in early childhood (summary by Pierce and Morse, 2012).
Abnormally decreased size of the anterior fontanelle with respect to age-dependent norms.
A discontinuity of the vertebral arch, i.e., of the posterior part of a vertebra.
A bending or abnormal curvature of the humerus.
Bowing (abnormal curvature) of the femur.
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of severe short stature and craniofacial dysmorphism (microcephaly, narrow face with flat cheeks, ptosis, prominent nose with a convex ridge, low-set ears with small or absent lobes, high-arched/cleft palate, micrognathia), associated with premature graying and loss of scalp hair, redundant, dry and wrinkled skin of the palms, premature senility and varying degrees of intellectual disability. Cryptorchidism and skeletal anomalies may also be observed. There have been no further descriptions in the literature since 1970.
Proximal radial shortening owing to a congenital defect of development.
A cone-shaped appearance of the epiphyses of the fingers of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
Bietti crystalline dystrophy (BCD) is a chorioretinal degeneration characterized by the presence of yellow-white crystals and/or complex lipid deposits in the retina and (to a variable degree) the cornea. Progressive atrophy and degeneration of the retinal pigment epithelium (RPE) / choroid lead to symptoms similar to those of other forms of retinal degeneration that fall under the category of retinitis pigmentosa and allied disorders, namely: reduced visual acuity, poor night vision, abnormal retinal electrophysiology, visual field loss, and often impaired color vision. Marked asymmetry between eyes is not uncommon. Onset is typically during the second to third decade of life, but ranges from the early teenage years to beyond the third decade. With time, loss of peripheral visual field, central acuity, or both result in legal blindness in most if not all affected individuals.
An exceedingly rare genetic neurological and developmental disorder reported in a very small number of patients with a poorly defined phenotype including iris coloboma, short stature, obesity, hypogonadism, post axial polydactyly, and intellectual disability. Hydrocephalus and facial dysostosis were also reported. The syndrome shares features with Bardet-Biedl syndrome. There have been no new descriptions in the literature since 1997.
A form of hemolytic anemia that occurs in repeated episodes.
An increased concentration of ammonia in the blood with sudden onset.
Repeated transient episodes of metabolic acidosis, that is, of the buildup of acid or depletion of base due to accumulation of metabolic acids.
Beta-aminoisobutyric acid (BAIB) is a product of pyrimidine catabolism. Excretion of BAIB in urine is a benign 'metabolic polymorphism' present in many human populations (Scriver and Perry, 1989).
Spasticity that increases in degree with time.
A lethal malformation syndrome reported in 2 brothers of first-cousin parents with characteristics of hydrocephalus, cardiac malformation, dense bones and unusual facies with down-slanting palpebral fissures, bulbous nose, broad nasal bridge, micrognathia and a long upper lip. Transmission is likely autosomal recessive. There have been no further descriptions in the literature since 1984.
Bare lymphocyte syndrome type II (BLS II) is an inherited disorder of the immune system categorized as a form of combined immunodeficiency (CID). People with BLS II lack virtually all immune protection from bacteria, viruses, and fungi. They are prone to repeated and persistent infections that can be very serious or life-threatening. These infections are often caused by ""opportunistic"" organisms that ordinarily do not cause illness in people with a normal immune system.BLS II is typically diagnosed in the first year of life. Most affected infants have persistent infections in the respiratory, gastrointestinal, and urinary tracts. Because of the infections, affected infants have difficulty absorbing nutrients (malabsorption), and they grow more slowly than their peers. Eventually, the persistent infections lead to organ failure. Without treatment, individuals with BLS II usually do not survive past early childhood.In people with BLS II, infection-fighting white blood cells (lymphocytes) are missing specialized proteins on their surface called major histocompatibility complex (MHC) class II proteins, which is where the condition got its name. Because BLS II is the most common and best studied form of a group of related conditions, it is often referred to as simply bare lymphocyte syndrome (BLS).
The patients are born with hair that falls out and is not replaced. Histologic studies show malformation of the hair follicles. Papillary lesions over most of the body and almost complete absence of hair are features.
Ataxia with oculomotor apraxia type 1 (AOA1) is characterized by childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. The first manifestation is progressive gait imbalance (mean age of onset: 4.3 years; range: 2-10 years), followed by dysarthria, then upper-limb dysmetria with mild intention tremor. Oculomotor apraxia, usually noticed a few years after the onset of ataxia, progresses to external ophthalmoplegia. All affected individuals have generalized areflexia followed by a peripheral neuropathy and quadriplegia with loss of ambulation about seven to ten years after onset. Hands and feet are short and atrophic. Chorea and upper-limb dystonia are common. Intellect remains normal in some individuals; in others, different degrees of cognitive impairment have been observed.
A reduced number of large myelinated nerve fibers.
Reduced functionality of the process in which a precursor cell type acquires the specialized features of a B cell. A B cell is a lymphocyte of B lineage with the phenotype CD19-positive and capable of B cell mediated immunity.
Bizygomatic (upper face) and bigonial (lower face) width greater than 2 standard deviations above the mean (objective); or an apparent increase in the width of the face (subjective).
The camptodactyly-arthropathy-coxa vara-pericarditis syndrome is an autosomal recessive condition characterized by the association of congenital or early-onset camptodactyly and noninflammatory arthropathy with synovial hyperplasia. Progressive coxa vara deformity and/or noninflammatory pericardial or pleural effusions are found in some patients (summary by Faivre et al., 2000).
A question about whether an individual is or was easily fatigued.
An abnormal enlargement of the proximal epiphysis of the femur.
Sclerosis (increased density) affecting vertebral end plates.
Arthrogryposis-like syndrome, also known as Kuskokwim disease, is a very rare congenital contracture disorder, reported exclusively in Yup'ik Eskimos of the Kuskokwim River delta region of Alaska, characterized by multiple contractures of large joints (predominantly the knees and ankles) that present at birth or during childhood but are lifelong; deformities of the spine, pelvis and feet; and sometimes proximally or distally displaced patellae and muscle atrophy in the limbs with contractures. Additional radiological features include mild vertebral wedging, elongation of the vertebral pedicle, and clubbing of the distal clavicle. An autosomal recessive pattern of inheritance has been suggested.
An arthrogryposis syndrome described in two siblings to date with the association of multiple congenital joint contractures (of the large joints, fingers and toes) and hyperkeratosis (i.e. thick, scaling and fissured skin) and death occurring in early infancy. There have been no further reports in the literature since 1993.
An extremely rare type of arthrogryposis multiplex congenita with the combination of multiple joint contractures with movement limitation and microstomia with a whistling appearance of the mouth that may cause feeding, swallowing and speech difficulties, a distinctive expressionless facies, severe developmental delay, central and autonomous nervous system dysfunction, occasionally Pierre-Robin sequence and lethality generally occurring during the first months of life.
Decreased distance from the nasal tip to the nasal base.
Arterial tortuosity syndrome (ATS) is characterized by the following: Severe and widespread arterial tortuosity of the aorta and middle-sized arteries (with an increased risk of aneurysms and dissections) and focal and widespread stenosis which can involve the aorta and/or pulmonary arteries. The risk for ischemic vascular events involving cerebrovascular circulation and the abdominal arteries is increased. In addition, large veins may be dilated and valvular regurgitation and mitral valve prolapse can occur. Craniofacial involvement with characteristic facies and high palate with dental crowding. Soft/doughy skin and other evidence of a generalized connective tissue disorder including skeletal findings (scoliosis, pectus excavatum/carinatum, joint laxity, knee/elbow contractures, arachnodactyly, camptodactyly); inguinal/abdominal wall hernia; sliding hiatal or diaphragmatic hernia; hypotonia; and ocular involvement (myopia, keratoconus).
A decreased concentration of arginine in the blood.
An extremely rare congenital limb malformation syndrome, described in only 3 patients to date with the association of hypoplasia or aplasia of the hand and foot phalanges, hemivertebrae and various urogenital and/or intestinal abnormalities (i.e. dysgenesis of the urogenital tract and rectum). There have been no further descriptions in the literature since 1991.
SOX2-related eye disorders are characterized by anophthalmia and/or microphthalmia that is usually bilateral, severe, and apparent at birth or by prenatal ultrasound examination. Other common findings include brain malformations, esophageal atresia, cryptorchidism and/or micropenis in males, and hypogonadotropic hypogonadism and/or pituitary hypoplasia. Postnatal growth failure, delayed motor development, and learning disability are common.
Underdevelopment of the anterior pituitary gland.
A defect in the ability to concentrate the urine.
Lipofuscin, a generic term applied to autofluorescent lipopigment, is a mixture of protein and lipid that accumulates in most aging cells, particularly those involved in high lipid turnover (e.g., the adrenal medulla) or phagocytosis of other cell types (e g., the retinal pigment epithelium or RPE; macrophage). This term pertains if there is an increase in the extraneuronal accumulation of lipofuscin (also known as autofluorescent lipoprotein) more than expected for the age of the patient.
Truncal obesity with onset during childhood, defined as between 2 and 10 years of age.
Alopecia universalis congenita is a severe autosomal recessive form of alopecia characterized by a complete absence of hair development affecting all scalp and body hair (Nothen et al., 1998). This rare disorder is clearly distinct from alopecia areata (AA1; 104000), which has an autoimmune basis with probable genetic predisposition.
Alopecia-mental retardation syndrome (APMR) is a rare autosomal recessive disorder in which affected individuals show loss of hair on the scalp, absence of eyebrows, eyelashes, and axillary and pubic hair, and mild to severe mental retardation (summary by Wali et al., 2007). Genetic Heterogeneity of Alopecia-Mental Retardation Syndrome Loci for alopecia-mental retardation syndrome have been mapped to chromosome 3q26.2-q26.31 (APMR2; 610422) and chromosome 18q11.2-q12.2 (APMR3; 613930).
The progressive development of an abnormally large skull.
A very rare syndrome associating microcephaly, micrognathia, oculocutaneous albinism, hypoplasia of the distal phalanx of fingers and agenesia of the distal end of the right big toe. It has been described in two siblings. Both brother and sister had psychomotor retardation and died in the course of a respiratory infection. The reported cases suggest that the condition is hereditary, and is transmitted as an autosomal recessive trait.
Syndrome with the association of microcephaly, low birth weight and severe intellectual deficit with dwarfism, small teeth and diabetes mellitus. Two cases have been described. Biochemical tests reveal the presence of high levels of alanine in the urine and elevated alanine, pyruvate and lactate levels in the blood.
PAGOD syndrome is a severe developmental syndrome with characteristics of multiple congenital anomalies including cardiovascular defects, pulmonary hypoplasia, diaphragmatic defects and genital anomalies. Since the first publication in 1991, only 11 patients have been described. Neonates with PAGOD syndrome present with several visceral anomalies: hypoplasia of right or left lung, diaphragmatic hernia, omphalocele, various cardiac anomalies including, amongst others atrial septal defect, left ventricular hypoplasia or ventricular septal defect and great vessels anomalies such as aortic hypoplasia and pulmonary artery hypoplasia or atresia. Cardiac and mediastinal structures may be in dextroposition. Ambiguous external genitalia can be observed in some cases and all patient's present gonadal agenesis or hypoplasia and developmental anomalies of Wolffian and Mullerian duct structures. Vitamin A deficiency has been suggested to play a role in the development of the syndrome. Almost all cases are sporadic.
Congenital defect with failure of the development of the cerebral white matter.
Adrenocortical carcinoma (ADCC) is a rare but aggressive childhood tumor, representing about 0.4% of childhood tumors, with a high incidence of associated tumors. ADCC occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome (130650) and is a component tumor in Li-Fraumeni syndrome (LFS; 151623).
The onset of puberty before the age of 9 years in boys.
Ambiguous genitalia in an individual with XX genetic gender.
21-hydroxylase deficiency is an inherited disorder that affects the adrenal glands. The adrenal glands are located on top of the kidneys and produce a variety of hormones that regulate many essential functions in the body. In people with 21-hydroxylase deficiency, the adrenal glands produce excess androgens, which are male sex hormones.There are three types of 21-hydroxylase deficiency. Two types are classic forms, known as the salt-wasting and simple virilizing types. The third type is called the non-classic type. The salt-wasting type is the most severe, the simple virilizing type is less severe, and the non-classic type is the least severe form.Males and females with either classic form of 21-hydroxylase deficiency tend to have an early growth spurt, but their final adult height is usually shorter than others in their family. Additionally, affected individuals may have a reduced ability to have biological children (decreased fertility). Females may also develop excessive body hair growth (hirsutism), male pattern baldness, and irregular menstruation.Approximately 75 percent of individuals with classic 21-hydroxylase deficiency have the salt-wasting type. Hormone production is extremely low in this form of the disorder. Affected individuals lose large amounts of sodium in their urine, which can be life-threatening in early infancy. Babies with the salt-wasting type can experience poor feeding, weight loss, dehydration, and vomiting. Individuals with the simple virilizing form do not experience salt loss.In both the salt-wasting and simple virilizing forms of this disorder, females typically have external genitalia that do not look clearly male or female (ambiguous genitalia). Males usually have normal genitalia, but the testes may be small.Females with the non-classic type of 21-hydroxylase deficiency have normal female genitalia. As affected females get older, they may experience hirsutism, male pattern baldness, irregular menstruation, and decreased fertility. Males with the non-classic type may have early beard growth and small testes. Some individuals with this type of 21-hydroxylase deficiency have no symptoms of the disorder.
Cytochrome P450 oxidoreductase deficiency is a disorder of hormone production. This condition specifically affects steroid hormones, which are needed for normal development and reproduction. The hormonal changes associated with cytochrome P450 oxidoreductase deficiency can affect the development of the reproductive system, skeleton, and other parts of the body. These signs and symptoms are usually present at birth or become apparent in early childhood.The signs and symptoms of cytochrome P450 oxidoreductase deficiency vary from mild to severe. Signs and symptoms of mild cases can include a failure to begin menstruation by age 16 (primary amenorrhea), an inability to have biological children (infertility) in both men and women, and a condition called polycystic ovarian syndrome (PCOS). PCOS is characterized by a hormonal imbalance in women that can lead to irregular menstruation, acne, excess body hair (hirsutism), and weight gain.People with moderate cases of cytochrome P450 oxidoreductase deficiency may have external genitalia that do not look clearly male or female (ambiguous genitalia), and they may have infertility. People with moderate cytochrome P450 oxidoreductase deficiency usually do not have skeletal abnormalities.The severe form of cytochrome P450 oxidoreductase deficiency is sometimes called Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis. Hormonal changes in affected males and females lead to the development of ambiguous genitalia or other genital abnormalities, as well as infertility. Severe cases are also characterized by skeletal abnormalities, particularly involving bones of the head and face. These include premature fusion of the skull bones (craniosynostosis), a flattened mid-face, a prominent forehead, and low-set ears. Other skeletal abnormalities can include joint deformities (contractures) that limit movement; unusually long, slender fingers (arachnodactyly); bowing of the thigh bones; and radiohumeral synostosis, which is a bone abnormality that locks the elbows in a bent position. A blockage of the nasal passages (choanal atresia), intellectual disability, and delayed development are also associated with the severe form of the disorder.Some women who are pregnant with fetuses affected by cytochrome P450 oxidoreductase deficiency experience mild symptoms of the disorder even though they themselves do not have the disorder. They may develop excessive body hair growth (hirsutism), acne, and a deep voice. These changes go away soon after delivery.
Trilobar skull configuration when viewed from the front or behind.
Presence of myoglobin in the urine following exercise.
An increase in the level of medium chain dicarboxylic acid in the urine.
A type of digital ulcer that manifests as an open sore on the surface of the skin at the tip of a finger or toe.
A bending or abnormal curvature of the distal portion of the femur.
A very rare congenital malformation syndrome with the association of facial and skeletal anomalies, severe intellectual deficit and occasional genitourinary anomalies. The cranio-facial malformations are numerous and variable and include brachycephaly or microbrachycephaly. Other skeletal malformations are also present, with syndactyly of fingers, hypoplastic toes, anomalies of feet structure and fibular hypoplasia. Short stature may be observed. Eye anomalies include bilateral ptosis, cataract and congenital glaucoma. In some male patients, hypospadias and bifid scrotum are reported. Patients suffer from potentially severe intellectual deficit and present with anomalies of the cortical gyration.
A multiple malformation syndrome in which mandibulofacial dysostosis and severe limb reduction defects are associated with complex malformations of different organs and systems especially the central nervous system, urogenital tract, heart, and lungs. The mandibulofacial defect causes death by respiratory distress. Limb reduction is severe and includes shoulder and pelvis hypoplasia, phocomelia with humerus hypoplasia, absent radius and ulna, complete absence of long bones of the legs, and various hand anomalies, predominantly preaxial reduction. These infants also show facial dysmorphism and ear anomalies. The condition is a rare with an autosomal recessive mode of inheritance. The prognosis is poor and this condition leads to death in utero or shortly after birth.
Abnormally reduced ability of T cells to perform their functions in cell-mediated immunity.
An increased susceptibility to candida infections, as manifested by a history of recurrent episodes of candida infections.
Abnormally reduced serum levels of alkaline phosphatase activity.
A morphologic finding indicating the presence of necrosis associated with an inflammatory infiltrate in a tissue sample.
A very rare form of acrofacial dysostosis, reported in two sisters to date, with characteristics of short stature, acrocephaly, ocular hypertelorism, ptosis of eyelids, ocular proptosis, downslanting palpebral fissures, high nasal bridge, anteverted nostrils, short philtrum, cleft palate, micrognathia, abnormal external ears, preauricular pits, mixed hearing loss, bulbous digits, metatarsus varus, pectus excavatum and various radiological abnormalities. Features of this syndrome were reported to overlap with otopalatodigital syndrome types 1 and 2. There have been no further descriptions in the literature since 1988.
Acrocephalopolydactylous dysplasia, or Elejalde syndrome, is a lethal multiple congenital disorder characterized by increased birth weight, globular body with thick skin, organomegaly, and fibrosis in multiple tissues (summary by Phadke et al., 2011).
Cleft (split into two parts) distal phalanx of thumb. [HPO:probinson]
Partial or complete duplication of one or more phalanx of big toe.
Any defect in the valve connecting the heart and the pulmonary artery.
A very rare multiple congenital anomalies syndrome with characteristics of limb deficiencies and renal anomalies that include split hand-split foot malformation, renal agenesis, polycystic kidneys, uterine anomalies and severe mandibular hypoplasia.
Ackerman syndrome has characteristics of pyramidal molar roots and taurodontism associated with variable anomalies. It has been described in two generations of one family. Both parents and their six siblings had pyramidal, taurodont or fused molar roots. Some of the patients also had hypotrichosis, an abnormal upper lip, thickened and wide philtrum, and/or juvenile glaucoma. Other features included entropion of the eyelid, syndactyly and clinodactyly of the fifth fingers.
Absence or underdevelopment of the metatarsal bones.
A lack of bone mineralization of the vertebral bodies.
A lack of ossification of the vertebral bodies.
An extremely rare genetic syndrome, reported in a few families to date with characteristics of the association of microcephaly, intellectual deficit and achalasia. Symptoms of achalasia include coughing, dysphagia, vomiting, failure to thrive and aspiration appearing in infancy/early-childhood.
Achalasia is a primary motor disorder of the esophagus. It is characterized by aperistalsis and a failure of the lower esophageal sphincter to relax due to a loss of inhibitory nitrinergic neurons in the esophageal myenteric plexus. Patients typically present with dysphagia, regurgitation, retrosternal pain, and substantial weight loss (Farrokhi and Vaezi, 2007; summary by Gockel et al., 2010).
Ablepharon-macrostomia syndrome is a congenital ectodermal dysplasia characterized by absent eyelids, macrostomia, microtia, redundant skin, sparse hair, dysmorphic nose and ears, variable abnormalities of the nipples, genitalia, fingers, and hands, largely normal intellectual and motor development, and poor growth (summary by Marchegiani et al., 2015).
Woolly hair (WH) refers to a group of hair shaft disorders that are characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, WH grows slowly and stops growing after a few inches. Under light microscopy, WH shows some structural anomalies, including trichorrhexis nodosa and tapered ends. WH can appear as part of several syndromes, such as Naxos disease (601214) and cardiofaciocutaneous syndrome (115150) (summary by Petukhova et al., 2009). See 278150 for a discussion of genetic heterogeneity of autosomal recessive woolly hair.
Any anomaly in the formation of the bony substance of the sternum.
A deviation from the normal rotation of the midgut during embryologic development with mislocalization of the small bowel.
A pseudoepiphysis is a secondary ossification center distinct from the normal epiphysis. The normal metacarpal epiphyses are located at the distal ends of the metacarpal bones. Accessory epiphyses (which are also known as pseudoepiphyses) can also occasionally be observed at the proximal ends of the metacarpals, usually involving the 2nd metacarpal bone.
Decreased density/number and/or decreased diameter of medial eyebrow hairs.
H-shaped crease in the fat pad of the chin.
DYT4 type primary dystonia has characteristics of predominantly laryngeal dystonia (manifesting as whispering dysphonia) and cervical dystonia (manifesting as torticollis). So far, the disease has been reported in one large Australian family. The age of onset varies from 13 to 37 years. The locus for DYT4 remains unknown. The disease is transmitted in an autosomal dominant manner.
A larger than normal amount or percentage of hematopoietic cells relative to marrow fat.
A clear, yellow, or brown, well-defined, dome-shaped elevation projecting from the surface of the iris. It is composed of hamartomatous melanocytic aggregates and is the most common ocular manifestation of neurofibromatosis type 1.
The presence in the axillary region (armpit) of an increased number of freckles, small circular spots on the skin that are darker than the surrounding skin because of deposits of melanin.
Waardenburg syndrome type 2 is an autosomal dominant auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi, which is seen in some other forms of WS (reviews by Read and Newton, 1997 and Pingault et al., 2010). Clinical Variability of Waardenburg Syndrome Types 1-4 Waardenburg syndrome has been classified into 4 main phenotypes. Waardenburg syndrome type 1 (WS1; 193500) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type 2 (WS2) is distinguished from type 1 by the absence of dystopia canthorum. WS type 3 (WS3; 148820) has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type 4 (WS4; 277580), also known as Waardenburg-Shah syndrome, has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010). Genetic Heterogeneity of Waardenburg Syndrome Type 2 Waardenburg syndrome type 2 is a genetically heterogeneous disorder. WS2B (600193) has been mapped to chromosome 1p, WS2C (606662) has been mapped to chromosome 8p23, WS2D (608890) is caused by mutation in the SNAI2 gene (602150) on chromosome 8q11, and WS2E (611584) is caused by mutation in the SOX10 gene (602229) on chromosome 22q13.
The appearance of yellow/white crystalline-like (hence the name) spots in the retina and thickening of the peripheral part of the vitreous.
Abnormal plantar flexion of the calcaneus relative to the longitudinal axis of the tibia. This results in the angle between the long axis of the tibia and the long axis of the heel bone (calcaneus) being greater than 90 degrees.
This is a postural deformity in which the foot is positioned up against the tibia. The heel (calcaneus) is positioned downward (that is, the ankle is flexed upward), and the heel is turned outward (valgus).
The presence of an increased number of twists and turns of the retinal blood vessels.
An abnormality of an internal carotid artery.
An anomaly of the sternum, also known as the breastbone.
Retinal vasculopathy with cerebral leukodystrophy is an adult-onset autosomal dominant disorder involving the microvessels of the brain and resulting in central nervous system degeneration with progressive loss of vision, stroke, motor impairment, and cognitive decline. Death occurs in most patients 5 to 10 years after onset. A subset of affected individuals have systemic vascular involvement evidenced by Raynaud's phenomenon, micronodular cirrhosis, and glomerular dysfunction (summary by Richards et al., 2007).
Upington disease has characteristics of Perthes-like pelvic anomalies (premature closure of the capital femoral epiphyses and widened femoral necks with flattened femoral heads), enchondromata and ecchondromata. It has been described in siblings from three generations of one family. Transmission is autosomal dominant.
An autosomal dominant ectodermal dysplasia syndrome, with characteristics of uncombable hair syndrome, congenital hypotrichosis and dental abnormalities such as oligodontia or hyperdontia and associated with early-onset cataract, retinal pigmentary dystrophy and brachydactyly with brachymetacarpia. Furthermore, hyperactivity and a mild intellectual deficit have been reported in affected patients.
Congenital hypoplasia of one or more proximal phalanx of finger.
Hair that is disorderly, stands out from the scalp, and cannot be combed flat.
Underdevelopment of the ulna. [HPO:curators]
Disproportionate short stature present from birth with dysplasia of the ulna and fibula. Curvatures of the forearm, radial head luxation, and tibial anomalies have also been described. The syndrome is transmitted in an autosomal dominant manner.
Tune deafness, or congenital amusia, is a lifelong deficient in music perception that cannot be explained by hearing loss, brain damage, intellectual deficiencies, or lack of exposure. The disorder affects predominantly the melodic pitch dimension (summary by Peretz et al., 2009). See 159300 for an opposite situation, that of musical perfect pitch.
Areas of the retina lacking pigmentation. Punched out areas of chorioretinal hypopigmentation less than 1 disc diameter in size and tending to be located in the midperiphery of the retina.
The presence of small depressions in the dental enamel.
Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening (hypertrophy) of the heart (cardiac) muscle. Thickening usually occurs in the interventricular septum, which is the muscular wall that separates the lower left chamber of the heart (the left ventricle) from the lower right chamber (the right ventricle). In some people, thickening of the interventricular septum impedes the flow of oxygen-rich blood from the heart, which may lead to an abnormal heart sound during a heartbeat (heart murmur) and other signs and symptoms of the condition. Other affected individuals do not have physical obstruction of blood flow, but the pumping of blood is less efficient, which can also lead to symptoms of the condition. Cardiac hypertrophy often begins in adolescence or young adulthood, although it can develop at any time throughout life.The symptoms of familial hypertrophic cardiomyopathy are variable, even within the same family. Many affected individuals have no symptoms. Other people with familial hypertrophic cardiomyopathy may experience chest pain; shortness of breath, especially with physical exertion; a sensation of fluttering or pounding in the chest (palpitations); lightheadedness; dizziness; and fainting.While most people with familial hypertrophic cardiomyopathy are symptom-free or have only mild symptoms, this condition can have serious consequences. It can cause abnormal heart rhythms (arrhythmias) that may be life threatening. People with familial hypertrophic cardiomyopathy have an increased risk of sudden death, even if they have no other symptoms of the condition. A small number of affected individuals develop potentially fatal heart failure, which may require heart transplantation.
An extremely rare familial bone deformity described only in Japanese patients to date. The deformity is bilateral in nearly half of patients (with bilateral involvement, the condition is symmetrical) and sometimes causes ulnar nerve palsy or cubitus varus.
The narrowing or partial blockage of a portion of the duodenum.
This syndrome has characteristics of triphalangeal thumbs and brachydactyly of the hands. Ectrodactyly of the feet and, more rarely, ectrodactyly of the hands were also reported in some family members. Transmission is autosomal dominant.
Syndrome with characteristics of triphalangeal thumbs, brachydactyly, camptodactyly, recurrent dislocation of the patellas and relatively short stature. It has been described in a mother and her three daughters.
Triosephosphate isomerase deficiency is an autosomal recessive multisystem disorder characterized by congenital hemolytic anemia, and progressive neuromuscular dysfunction beginning in early childhood. Many patients die from respiratory failure in childhood. The neurologic syndrome is variable, but usually includes lower motor neuron dysfunction with hypotonia, muscle weakness and atrophy, and hyporeflexia. Some patients may show additional signs such as dystonic posturing and/or spasticity. Laboratory studies show intracellular accumulation of dihydroxyacetone phosphate (DHAP), particularly in red blood cells (summary by Fermo et al., 2010).
A rudimentary tag of sking often containing ear tissue including a core of cartilage and located just anterior to the auricle (outer part of the ear).
Deformity of the hip characterized by enlargement and deformation of the FEMUR HEAD and FEMUR NECK, often with associated changes in the ACETABULUM. These changes may be secondary to other diseases (e.g. LEGG-PERTHES DISEASE; ARTHRITIS; HIP DISLOCATION, CONGENITAL) or TRAUMA.
Muscular hypotonia (abnormally low muscle tone) manifesting in infancy.
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Familial multiple discoid fibromas (FMDF) is an autosomal dominant dermatologic condition characterized by the appearance of multiple skin-colored, firm, flat or dome-shaped papules on the pinnae and the central area of the face in childhood or adolescence. Most lesions show a hair at or just outside the periphery, and many have a telangiectatic surface (summary by Starink et al., 2012). Trichodiscoma, as this lesion was first described by Pinkus et al. (1974), is a small benign fibrovascular tumor of the dermal part of the hair disc. The hair disc is a richly vascularized dermal pad in close association with a hair. It is supplied by a thick myelinated nerve and is considered to be a slow-adapting mechanoreceptor. Trichodiscomas are small, flat or dome-shaped, skin-colored, firm papules with a telangiectatic surface. Many of the lesions show a hair at the periphery or just outside it. Starink et al. (2012) renamed the lesion 'discoid fibroma' as a clarification of the histologic findings. FMDF is similar to, but histologically and genetically distinct from, Birt-Hogg-Dube syndrome (BHD; 135150), which is characterized by fibrofolliculomas as well as renal and pulmonary cysts.
Absence of the spongy bone structure (or tissue) of the internal part of the skull cap (i.e., of the calvarial diploe).
Essential tremor may be the most common human movement disorder. The main feature of essential tremor is postural tremor of the arms, but the head, legs, trunk, voice, jaw, and facial muscles also may be involved. Aggravated by emotions, hunger, fatigue, and temperature extremes, the condition may cause a functional disability or even incapacitation. Autosomal dominant inheritance can be demonstrated in most families (summary by Higgins et al., 1997). Deng et al. (2007) provided a detailed review of the genetics of essential tremor. Genetic Heterogeneity of Essential Tremor Other forms of hereditary essential tremor include ETM2 (602134), mapped to chromosome 2p25-p22; ETM3 (611456), mapped to chromosome 6p23; ETM4 (614782), caused by mutation in the FUS gene (137070) on chromosome 16p11; and ETM5 (616736), caused by mutation in the TENM4 gene (610084) on chromosome 11q14.
Geniospasm is characterized by spontaneous intermittent involuntary quivering or trembling of the chin that is intensified by stress or anxiety. The movements are first noticed in infancy or childhood and usually abate by late adulthood (Wadlington, 1958; Danek et al., 1991).
Torus palatinus (TP) is a spindle-shaped bony elevation along the midline of the hard palate. Torus mandibularis (TM) is a bony elevation along the mandible generally just below the lower premolars. Both exostoses usually appear in the form of a series of swellings (summary by Suzuki and Sakai, 1960).
Tibial torsion (twisting of the tibia) can cause toeing in or out, depending on whether it is internal or external torsion. Although some degree of internal tibial torsion is present in almost all infants because of the intrauterine position, it usually corrects spontaneously. Persistence of internal tibial torsion may be inherited as an autosomal dominant trait (summary by Fitch, 1974).
Occlusion of the lumen of a vein by a thrombus that has migrated from a distal site via the blood stream.
ANKRD26-related thrombocytopenia is characterized by lifelong mild-to-moderate thrombocytopenia with a normal platelet size and no syndromic associations. Most individuals have normal hemostasis or a mild bleeding phenotype and do not develop severe spontaneous bleeding. Some individuals may have concomitant erythrocytosis and leukocytosis. The risk for myeloid malignancies (including myelodysplastic syndrome, acute myelogenous leukemia, and chronic myelogenous leukemia) is increased in individuals with ANKRD26 pathogenic variants.
Platelet-type bleeding disorder-17 is an autosomal dominant disorder characterized by increased bleeding tendency due to abnormal platelet function. It is a type of 'gray platelet syndrome' because the platelets appear abnormal on light microscopy. Electron microscopy shows decreased or absent alpha-granules within platelets, and bone marrow biopsy shows increased numbers of abnormal megakaryocytes, suggesting a defect in megakaryopoiesis and platelet production. The bleeding severity is variable (summary by Monteferrario et al., 2014). For a discussion of genetic heterogeneity of platelet-type bleeding disorder, see BDPLT1 (231200).
BDPLT16 is an autosomal dominant form of congenital macrothrombocytopenia associated with platelet anisocytosis. It is a disorder of platelet production. Affected individuals may have no or only mildly increased bleeding tendency. In vitro studies show mild platelet functional abnormalities (summary by Kunishima et al., 2011 and Nurden et al., 2011).
A short-rib dysplasia with characteristics of thoracic dystrophy, laryngeal stenosis and a small pelvis. Less than 10 cases have been reported in the literature so far. Patients present with severe respiratory distress (requiring intubation) during the neonatal period. The rib shortening is less severe than in Jeune syndrome and the thorax is characteristically small, narrow and bell-shaped. The pelvis is reduced in all dimensions and the combination of the thorax anomalies and the small pelvis give the appearance of a protruding abdomen. Subglottic stenosis has also been described but it remains unclear whether this is a congenital anomaly or is secondary to long-term intubation. Transmission is autosomal dominant.
Irregular surface of the normally relatively smooth border between the distal part of the ribs and the costal cartilages, which are bars of hyaline cartilage that connect the ribs to the sternum.
An abnormal narrowing of the foramen magnum.
Telangiectasia (small dilated blood vessels) located in the fingerpads at the tips of the fingers.
Syringomyelia is characterised by cerebrospinal fluid (CSF)-filled cavities (syrinx) inside the spinal cord, either as a result of a known cause (secondary syringomyelia, SS) or, more rarely, due to an unknown cause (primary syringomyelia, PS).
Blau syndrome is characterized by the triad of granulomatous arthritis, uveitis, and dermatitis. First described in 1985, it was considered to be distinct from sarcoidosis due to the early age of onset and autosomal dominant inheritance pattern. Published reports of sporadic cases of children with 'early-onset sarcoidosis' (EOS) with granulomatous involvement of different organs, primarily affecting joints, eyes, and skin, were suspected to represent the same disorder because the patients' characteristics were nearly identical. Subsequently, identical NOD2 mutations were identified in patients with Blau syndrome as well as in patients diagnosed with EOS, confirming earlier suspicions that they represented the same disease (summary by Borzutzky et al., 2010). Unlike older children diagnosed with sarcoidosis, these patients have no apparent pulmonary involvement; however, the disease is progressive and may result in severe complications such as blindness and/or joint destruction (Shetty and Gedalia, 1998).
Tarsal-carpal coalition syndrome is a rare, inherited bone disorder that affects primarily the hands and feet. Several individual bones make up each wrist (carpal bones) and ankle (tarsal bones). In tarsal-carpal coalition syndrome, the carpal bones fuse together, as do the tarsal bones, which causes stiffness and immobility of the hands and feet. Symptoms of the condition can become apparent in infancy, and they worsen with age. The severity of the symptoms can vary, even among members of the same family.In this condition, fusion at the joints between the bones that make up each finger and toe (symphalangism) can also occur. Consequently, the fingers and toes become stiff and difficult to bend. Stiffness of the pinky fingers and toes (fifth digits) is usually noticeable first. The joints at the base of the pinky fingers and toes fuse first, and slowly, the other joints along the length of these digits may also be affected. Progressively, the bones in the fourth, third, and second digits (the ring finger, middle finger, and forefinger, and the corresponding toes) become fused. The thumb and big toe are usually not involved. Affected individuals have increasing trouble forming a fist, and walking often becomes painful and difficult. Occasionally, there is also fusion of bones in the upper and lower arm at the elbow joint (humeroradial fusion). Less common features of tarsal-carpal coalition syndrome include short stature or the development of hearing loss.
Liebenberg syndrome is an upper limb malformation characterized by the combination of dysplastic elbow joints and the fusion of wrist bones with consequent radial deviation (summary by Spielmann et al., 2012).
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
A progressive type of conductive deafness.
Stapes ankylosis refers to congenital or acquired fixation of the stapes (the stirrup-shaped small bone or ossicle in the middle ear), which is associated with conductive hearing resulting from impairment of the sound-conduction mechanism (the external auditory canal, tympanic membrane, and/or middle-ear ossicles).
An abnormal narrowing of the spinal canal.
A limitation of the ability to place the forearm in a position such that the palm faces anteriorly (supination) and to place the forearm in a position such that the palm faces posteriorly (pronation).
Absence or underdevelopment of the distal phalanges.
Aplasia (absence) of the distal phalanges.
A very rare congenital limb malformation with characteristics of postaxial syndactyly of hands and feet, associated with metacarpal and metatarsal fusion of fourth and fifth digits. So far, less than ten reports have been described in the literature. Soft tissue syndactyly (involving the third and fourth fingers and the second and third toes) may be present. The locus associated with SD5 maps to 2q31-q32. Mutations in the HOXD13 gene may be causative. The condition is inherited as an autosomal dominant trait.
Absence of the distal interphalangeal flexion creases of the fingers.
A very rare congenital distal limb malformation with characteristics of complete bilateral syndactyly involving all digits 1 to 5. So far, only four reports have been described in the literature. A frequent association with polydactyly (with six metacarpals and six digits) has been reported. Feet are affected occasionally. The SD4 locus maps to 7q36. The condition is inherited as an autosomal dominant trait.
A rare congenital distal limb malformation with complete and bilateral syndactyly between the fourth and fifth fingers. In most cases, it is a soft tissue syndactyly, but occasionally the distal phalanges may be fused. The feet are not affected. Inherited in an autosomal dominant manner.
Y-shaped metacarpals are the result of a partial fusion of two metacarpal bones, with the two arms of the Y pointing in the distal direction. Y-shaped metacarpals may be seen in combination with polydactyly.
An exceedingly rare syndrome described in one family and with characteristics of proximal symphalangism and multiple hand and feet disorders (syndactyly, clinodactyly, hypoplasia of the thenar and hypothenar eminences and a distinctive dermatoglyphic pattern). There have been no further descriptions in the literature since 1981.
Reduced muscle mass on the ulnar side of the palm, that is, reduction in size of the hypothenar eminence.
Distal symphalangism is ankylosis or rigidity of the distal interphalangeal joints of the hands and/or the feet (summary by Poush, 1991).
A variable severity of phenotypic features.
Hemangioma, a benign tumor of the vascular endothelial cells, occurring in the face.
A multiple congenital anomalies syndrome with characteristics of wormian bones, dextrocardia and short stature due to a growth hormone deficiency. Additional manifestations that have been reported include brachycamptodactyly, kidney hypoplasia, bilateral cryptorchidism, midshaft hypospadias, imperforate anus/anorectal agenesis, body asymmetry, mild developmental delay, hemimegalencephaly and facial dysmorphism, such as hypotelorism, downslanting palpebral fissures, low-set and posteriorly angulated ears, depressed nasal bridge and microstomia.
Strabismus, a misalignment of the eyes also referred to as 'squint,' is one of the most common ocular disorders in humans, affecting 1 to 4% of the population. It is frequently associated with amblyopia (uniocular visual neglect) (Parikh et al., 2003). Strabismus is also a feature of several syndromes, including congenital fibrosis of extraocular muscles (see, e.g., CFEOM1; 135700), Duane retraction syndrome (126800), and chronic progressive external ophthalmoplegia with myopathy (530000).
Stormorken syndrome is an autosomal dominant disorder characterized by mild bleeding tendency due to platelet dysfunction, thrombocytopenia, anemia, asplenia, tubular aggregate myopathy, congenital miosis, and ichthyosis. Additional features may include headache or recurrent stroke-like episodes (summary by Misceo et al., 2014).
Cryohydrocytosis is an exceedingly rare condition characterized by a mild stomatocytic hemolytic state with hyperbilirubinemia. A hallmark of this condition is that red blood cells (RBCs) lyse on storage at 4 degrees centigrade. RBC cation permeability is increased at 37 degrees centigrade, and the cells also accumulate sodium in the cold (summary by Coles et al., 1999). Patients present with fatigue, mild anemia, and pseudohyperkalemia due to a potassium leak from the RBCs (summary by Bogdanova et al., 2010). For a discussion of clinical and genetic heterogeneity of the hereditary stomatocytoses, see 194380.
Overhydrated hereditary stomatocytosis is a variably compensated macrocytic hemolytic anemia of fluctuating severity, characterized by circulating erythrocytes with slit-like lucencies (stomata) evident on peripheral blood smears. OHST red cells exhibit cation leak, resulting in elevated cell Na+ content with reduced K+ content, with increased ouabain-resistant cation leak fluxes in the presence of presumably compensatory increases in ouabain-sensitive Na(+)-K(+) ATPase activity, and red cell age-dependent loss of stomatin/EBP7.2 (EBP72; 133090) from the erythroid membrane. Clinically, patients with OHST exhibit overhydrated erythrocytes and a temperature-dependent red cell cation leak. The temperature dependence of the leak is 'monotonic' and has a steep slope, reflecting the very large leak at 37 degrees centigrade (summary by Bruce, 2009 and Stewart et al., 2011). For a discussion of clinical and genetic heterogeneity of the hereditary stomatocytoses, see 194380.
Stiff skin syndrome is characterized by hard, thick skin, usually over the entire body, which limits joint mobility and causes flexion contractures. Other occasional findings include lipodystrophy and muscle weakness (Loeys et al., 2010). Patients with similar phenotypes involving stiff skin have been described; see, e.g., familial progressive scleroderma (181750), symmetric lipomatosis (151800), and congenital fascial dystrophy (228020).
Rare syndrome with manifestation of progressive sensorineural hearing loss due to severe cochleosaccular degeneration and cataract. So far reported in two families. Transmission is autosomal dominant.
The classification for headache disorders of the International Headache Society (1988) listed the following criteria for cluster headache (CH): at least 5 attacks of severe unilateral orbital, supraorbital, and/or temporal pain, lasting 15 to 180 minutes, associated with at least 1 of 8 local autonomic signs, and occurring once every other day to 8 per day. Approximately 85% of CH patients have the episodic subtype, in which the headaches occur in cluster periods lasting from 7 days to 1 year and separated by attack-free intervals of 1 month or more. The remainder of patients have the chronic subtype, in which attacks recur for greater than 1 year without remission or with remissions lasting less than 1 month (Lipton et al., 2004).
A rhizo-mesomelic dysplasia with characteristics of rhizomelic short stature in combination with lateral clavicular defects. Additional manifestations include brachydactyly with bilateral clinodactyly and hypoplastic middle phalanx of the fifth digit. The syndrome has been reported in one family (mother and son) and is suspected to be transmitted in an autosomal dominant manner. There have been no further descriptions in the literature since 1988.
A moderate degree of short stature, more than -3 SD but not more than -4 SD from mean corrected for age and sex.
Delayed maturation and calcification of the pubic bone.
An ectodermal dysplasia syndrome with the association of abnormalities of the eyelids, lips, and teeth. These anomalies include lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate and conical teeth. Additional occasional features include hypertelorism, lagophthalmos, imperforate anus, and syndactyly. Prevalence is unknown. Over 50 cases have been described in literature to date. Transmission is autosomal dominant with 100% penetrance.
Nonsyndromic cleft lip with or without cleft palate is a complex disease with a wide phenotypic spetrum ranging from notches of the vermilion and/or grooves in the philtrum to complete unilateral and bilateral clefts of the lip and palate (summay by Neiswanger et al., 2007). Genetic Heterogeneity of Orofacial Cleft Isolated cleft lip with or without cleft palate (CL/P) is genetically heterogeneous. The OFC1 locus has been mapped to chromosome 6p24. Other CL/P loci have been mapped to 2p13 (OFC2; 602966), 19q13 (OFC3; 600757), 4q (OFC4; 608371), 13q33.1-q34 (OFC9; 610361), 8q24.3 (OFC12; 612858), and 1p33 (OFC13; 613857). OFC5 (608874) is caused by mutation in the MSX1 gene (142983) on 4p16; OFC6 (608864) is associated with variation in an enhancer of the IRF6 gene (607199) on 1q; OFC7 (see 225060) is associated with mutation in the NECTIN1 gene (600644) on 11q23; OFC8 (618149) is caused by mutation in the TP63 gene (603273) on 3q28; OFC10 (613705) is associated with haploinsufficiency of the SUMO1 gene (601912) on 2q33; OFC11 (600625) is caused by mutation in the BMP4 gene (112262) on 14q22; OFC14 (615892) is associated with a 273-kb deleted region on 1p31; and OFC15 (616788) is caused by mutation in the DLX4 gene (601911) on 17q21. A common polymorphism in the MTR gene (156570.0008) has been associated with susceptibility to orofacial clefting. Cleft lip with or without cleft palate has been found in association with gastric cancer (see 137215) in individuals with mutation in the CDH1 gene (192090).
Depression located on the vermilion of the lower lip, usually paramedian.
Choroidal osteoma is a benign tumor found in the peripapillary region, most characteristically in one eye of otherwise healthy, young females. Histopathologic changes include bone formation with trabeculae, blood-filled cavernous spaces, and cells typical of bone formation, i.e., osteoblasts, osteocytes, and osteoclasts.
The presence of reduced numbers of intrahepatic bile duct than normal.
Butterfly vertebrae have a cleft through the body of the vertebrae and a funnel shape at the ends.
Inferior malposition of the lower eyelid margin without eyelid eversion.
Sudden and involuntary contractions of one or more muscles brought on by exposure to cold temperatures.
Dysplasia of the cervical vertebral column.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the calcaneus.
Hereditary cerebral amyloid angiopathy is a condition that can cause a progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. Due to neurological decline, this condition is typically fatal in one's sixties, although there is variation depending on the severity of the signs and symptoms. Most affected individuals die within a decade after signs and symptoms first appear, although some people with the disease have survived longer.There are many different types of hereditary cerebral amyloid angiopathy. The different types are distinguished by their genetic cause and the signs and symptoms that occur. The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed.The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. Stroke is frequently the first sign of the Dutch type and is fatal in about one third of people who have this condition. Survivors often develop dementia and have recurrent strokes. About half of individuals with the Dutch type who have one or more strokes will have recurrent seizures (epilepsy).People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. Individuals with the Piedmont type may have one or more strokes and typically experience impaired movements, numbness or tingling (paresthesias), confusion, or dementia.The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. Strokes associated with the Icelandic type usually occur earlier than the other types, with individuals typically experiencing their first stroke in their twenties or thirties.Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. Strokes are also uncommon in individuals with the Iowa type. This type is characterized by memory loss, problems with vocabulary and the production of speech, personality changes, and involuntary muscle twitches (myoclonus).Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. Strokes are uncommon in these types. People with the Danish type may also have clouding of the lens of the eyes (cataracts) or deafness.
Compression of the CELIAC ARTERY by the median arcuate ligament, a fibrous band of the DIAPHRAGM, causing abdominal pain after eating and weight loss. OMIM: 116870
Zonular cataracts are defined to be cataracts that affect specific regions of the lens.
Mutations in the EPHA2 gene have been found to cause multiple types of cataract, which have been described as posterior polar, congenital total, complete, and age-related cortical. The preferred title/symbol of this entry was formerly 'Cataract, posterior polar, 1; CTPP1,' and 'Cataract, Age-Related Cortical, 2; ARCC2' was formerly a distinct entry.
Mutations in the GJA8 gene have been found to cause several types of autosomal dominant cataract, which have been described as congenital, zonular pulverulent, nuclear progressive, nuclear pulverulent, stellate nuclear, nuclear total, total, and posterior subcapsular. Cataract associated with microcornea, sometimes called the cataract-microcornea syndrome, is also caused by mutation in the GJA8 gene. Before it was known that mutation in the GJB8 gene caused multiple types of cataract, this entry was titled 'Cataract, zonular pulverulent, 1,' with the symbols CZP1, CZP, and CAE1.
The association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Clinical findings include a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye, and an inherited cataract, which is most often bilateral posterior polar with opacification in the lens periphery. The cataract progresses to form a total cataract after visual maturity has been achieved, requiring cataract extraction in the first to third decade of life. The syndrome can be associated with other rare ocular manifestations, including myopia, iris coloboma, sclerocornea and Peters anomaly. Transmission is in most cases autosomal dominant, but cases of autosomal recessive transmission have recently been described. There is marked genetic heterogeneity. Mutations have been described in several crystallin genes (CRYAA, CRYBB1, CRYGD), and in the gap junction protein alpha 8 gene (GJA8).
A kind of nuclear cataract characterized by fiberglasslike or needlelike crystals projecting in different directions, through or close to the axial region of the lens.
The Volkmann type of cataract has been variously described as progressive, central, or zonular, with opacities in the embryonic, fetal, and juvenile nucleus and around the anterior and posterior Y-suture. Expression is highly variable, ranging from hardly recognizable opacities in the lens to dense cataracts. Affected members may thus be unaware of having the disease (Eiberg et al., 1995). The preferred title/symbol of this entry was formerly 'Cataract, Congenital, Volkmann Type; CCV.'
Absence or underdevelopment of the corpus callosum.
Flatness of the supraorbital portion of the frontal bones.
The presence of multiple creases on the palm of the hand (more than the normal three major creases (distal transverse crease, proximal transverse crease, and thenar crease).
A soft tissue continuity in the A/P axis between two digits that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two digits that lies significantly distal to the flexion crease that overlies the metacarpophalangeal or metatarsophalangeal joint of the adjacent digits.
Campomelic dysplasia (CD) is a skeletal dysplasia characterized by distinctive facies, Pierre Robin sequence with cleft palate, shortening and bowing of long bones, and clubfeet. Other findings include laryngotracheomalacia with respiratory compromise and ambiguous genitalia or normal female external genitalia in most individuals with a 46,XY karyotype. Many affected infants die in the neonatal period; additional problems identified in long-term survivors include short stature, cervical spine instability with cord compression, progressive scoliosis, and hearing impairment.
A rarer variant of campomelic dysplasia. The characteristics match campomelic dysplasia except that long bone curvature is not present (acampomelia).
An abnormal anterior bending or curvature of the tibia.
An extremely rare brachydactyly syndrome with characteristics of short broad hands and feet with brachydactyly associated with congenital flexion contractures of the proximal and/or distal interphalangeal joints of the fingers, as well as syndactyly of feet. Polydactyly, septate vagina and urinary incontinence were also occasionally reported. Camptobrachydactyly has been described in 18 members of 1 family, suggesting an autosomal dominant inheritance. There have been no further descriptions in the literature since 1972.
Bilateral striopallidodentate calcinosis, also known as idiopathic basal ganglia calcification (IBGC), is characterized by the accumulation of calcium deposits in different brain regions and is associated with a neurodegenerative clinical phenotype. The changes seen in IBGC occur in the absence of calcium or parathyroid hormone (PTH; 168450) metabolic disorders, such as hypoparathyroidism (see 146200) or pseudohypoparathyroidism (PHP; see 103580). See also the adult-onset form (213600), which is sometimes erroneously referred to as 'Fahr disease.'
The presence of six or more cafe-au-lait spots.
A type of third degree heart block in which the escape rhythm arises at a relatively low part of the conduction system (below the atrioventricular node), which produces a wide QRS complex.
Gustatory lacrimation results from an aberrant innervation of fibres from the seventh cranial nerve to the pterygopalatine ganglion which are destined originally for the submandibular ganglion. This aberrant innervation leads to uncontrollable tearing while eating or in anticipation of a meal.
Benign congenital lesion of the supraauricular soft tissue consisting of a blind-ending narrow tube or pit.
Congenital developmental defect arising from the primitive branchial apparatus.
Bony fusion of malleus, incus, and stapes.
A very rare malformation syndrome with characteristics of short stature, hypoplastic fifth digits with tiny dysplastic nails, facial dysmorphism with coarse features including a wide mouth and broad nose, and mild intellectual disability. It has been suggested that Coffin-Siris syndrome and BOD syndrome are perhaps allelic variants.
Underdevelopment (hypoplasia) of the fourth toe.
Shortening of the middle parts of the arm in relation to the upper and terminal segments.
Syndrome that resembles type A1 brachydactyly (variable shortening of the middle phalanges of all digits) with associated symphalangism (producing a distal phalanx with the shape of a chess pawn). Scoliosis, clubfoot and tall stature are also characteristic. The syndrome has been described in one family with five affected individuals from three successive generations. Transmission appears to be autosomal dominant.
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease on both hands.
Absence of one or more middle phalanx of a finger.
A morphological abnormality of distal phalanges such that they have the appearance of chess pawns.
Ectrodactyly (split-hand/foot malformation) associated with fibular hypoplasia/aplasia is a rare disorder that appears to be inherited in an autosomal dominant fashion with reduced penetrance and variable expression (Evans et al., 2002). A form of fibular hypoplasia/aplasia associated with oligosyndactyly and tibial campomelia has been reported (FATCO syndrome; 246570). Split-hand/foot malformation associated with tibial hypoplasia/aplasia has also been described (see SHFLD1, 119100).
In type E brachydactyly, shortening of the fingers is mainly in the metacarpals and metatarsals.
The Osebold-Remondini syndrome is a bone dysplasia with mesomelic shortness of limbs and, hence, shortness of stature, absence or hypoplasia of second phalanges with synostosis of the remaining phalanges, carpal and tarsal coalitions, and apparently no other anomalies (summary by Opitz and Gilbert, 1985).
Abnormally developed (dysplastic) distal epiphysis of the radius.
An abnormality of the tarsus are the cluster of seven bones in the foot between the tibia and fibula and the metatarsus, including the calcaneus (heel) bone and the talus (ankle) bone.
Brachydactyly type A5 (BDA5) is a very rare congenital malformation of the digits characterized by absence of the middle phalanges (usually of digits 2 to 5), nail dysplasia and duplicated terminal phalanx of the thumb.
A type of brachydactyly characterized by brachymesophalangy affecting mainly the 2nd and 5th digits.
Hypoplasia of the second finger, also known as the index finger.
In the classification of the brachydactylies, the analysis by Bell (1951) proved highly useful. The type A brachydactylies of Bell have the shortening confined mainly to the middle phalanges. In the A1 type, the middle phalanges of all the digits are rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. Genetic Heterogeneity of Brachydactyly Type A1 BDA1B (607004) has been mapped to chromosome 5. BDA1C (615072) is caused by mutation in the GDF5 gene (601146) on chromosome 20q11. BDA1D (616849) is caused by mutation in the BMPR1B gene (603248) on chromosome 4q22.
The term distal symphalangism refers to a bony fusion of the distal and middle phalanges of the digits of the hand, in other words the distal interphalangeal joint (DIJ) is missing which can be seen either on x-rays or as an absence of the distal interphalangeal finger creases.
Underdevelopment (hypoplasia) of the proximal phalanx of big toe.
Ballard syndrome has characteristics of hypoplasia of the distal phalanges of the ulnar side of the hand and shortening of one or more metacarpals. In contrast to brachydactyly type E, patients with Ballard syndrome have normal stature. The syndrome has been described in 12 members from four generations of one family. Transmission appears to be autosomal dominant.
A very rare autosomal dominant heart-hand syndrome with characteristics of bisymmetric brachydactyly accompanied by long thumbs, joint anomalies (restriction of motion at the shoulder and metacarpophalangeal joints) and cardiac conduction defects. Additional features include small hands and feet, clinodactyly, narrow shoulders with short clavicles, pectus excavatum and mild shortness of the limbs, cardiomegaly and murmur of pulmonic stenosis. It has been described in four family members from three generations, with no new cases having been reported since 1981.
The hypertension and brachydactyly syndrome is characterized by brachydactyly type E, severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, altered baroreflex blood pressure regulation, and death from stroke before age 50 years when untreated (summary by Maass et al., 2015).
The diagnostic hallmarks of Weismann-Netter syndrome (WNS) are anterior bowing of the diaphyses of the tibia and fibula, broadening or 'tibialization' of the fibula, posterior cortical thickening of both bones, and short stature. The diaphyses of other long bones may be similarly affected, but usually to a milder degree. Some WNS patients have also displayed mental retardation (summary by Peippo et al., 2009).
Diaphyseal medullary stenosis with malignant fibrous histiocytoma is an autosomal dominant bone dysplasia characterized by pathologic fractures due to abnormal cortical growth and diaphyseal medullary stenosis. The fractures heal poorly, and there is progressive bowing of the lower extremities. In 2 families, affected individuals also showed a limb-girdle myopathy, with muscle weakness and atrophy. Approximately 35% of affected individuals develop an aggressive form of bone sarcoma consistent with malignant fibrous histiocytoma or osteosarcoma. Thus, the disorder may be considered a tumor predisposition syndrome (summary by Camacho-Vanegas et al., 2012).
Bone dysplasia due to autosomal dominant mutation(s) in the P4HB gene, encoding prolyl 4-hydroxylase subunit beta, or autosomal recessive mutation(s) in the SEC24D gene, encoding SEC24 homolog D, COPII coat complex component. This condition is characterized by bone fragility, growth failure, craniosynostosis, hydrocephalus, and distinctive facial features, including marked frontal bossing, blue sclerae, ocular proptosis, midface hypoplasia, and micrognathia.
A chronic form of disseminated intravascular coagulation in which a persistent weak or intermittent activating stimulus is present and destruction and production of coagulation factors and platelets are balanced.
Overproduction of gonadotropins (FSH, LH) by the anterior pituitary gland.
Primary basilar impression of the skull is a developmental defect of the cranium in which there is invagination of the foramen magnum upward into the posterior cranial fossa. Basilar impression is often associated with other malformations of the notochord and craniovertebral junction, such as occipitalization of the atlas, Klippel-Feil anomaly (see 118100), Chiari type I malformation (118420), and syringomyelia (186700) (Paradis and Sax, 1972; Bhangoo and Crockard, 1999). Secondary basilar impression occurs as a result of generalized skeletal diseases, including hyperparathyroidism (see 145000), Paget disease (see 167250), and osteogenesis imperfecta (see, e.g., 166200). Platybasia refers to a skull base with an abnormally obtuse angle between the planes of the clivus and the anterior fossa. Platybasia may occur in basilar impression, but it is not of medical significance on its own (Bhangoo and Crockard, 1999). Historically, basilar impression was defined radiologically by numerous parameters, including the lines defined by Chamberlain (1939), McGregor (1948), and Fischgold and Metzger (1952), and the angle defined by Bull et al. (1955).
Polyp-like protrusions which are histologically hamartomas located in the stomach.
Hypoplastic (short) distal phalanx of the thumb.
A synostosis syndrome reported in a single Hungarian family in which members of 3 generations showed lunotriquetral synostosis, clinodactyly, clinometacarpy, brachymetacarpy and leptometacarpy (thin diaphysis). It appeared to be a unique dominant mutation. There have been no further descriptions in the literature since 1965.
A rare hereditary red cell membrane defect characterised by the presence of oval-shaped erythrocytes. Most patients are asymptomatic or occasionally have mild symptoms such as pallor, jaundice, anaemia and gallstones. The disease is common in Southeast Asian and Western Pacific countries and can occur at any age. Results from a 27 bp deletion in the SLC4A1 gene, localised on chromosome 17q21.31 (SLC4A1del27 mutation). This gene codes for a band 3 anion transport protein which is the bicarbonate/chloride exchanger in red blood cell membranes and defects in this protein cause membrane rigidity. The disease follows an autosomal dominant pattern of inheritance.
Fasciculations affecting the tongue muscle and the musculature of the face.
A rare autosomal dominant inherited chorioretinal degenerative disease presenting at birth or during infancy. The disease has characteristics of progressive bilateral retinal and choroidal atrophy which appears as lesions on the optic nerve and peripheral ocular fundus and leads to loss of central vision. Congenital anterior polar cataracts are sometimes associated with this disease. There is evidence this disease is caused by heterozygous mutation in the TEA domain family member-1 gene (TEAD1) on chromosome 11p15.
Secundum atrial septal defect (ASD) is a common congenital heart malformation that occurs as an isolated anomaly in 10% of individuals with congenital heart disease. Uncorrected ASD can cause pulmonary overcirculation, right heart volume overload, and premature death (summary by Benson et al., 1998). Genetic Heterogeneity of Atrial Septal Defect The ASD1 locus has been mapped to chromosome 5p. Other forms of atrial septal defect that are associated with other congenital heart disease but no conduction defects or noncardiac abnormalities include ASD2 (607941), caused by mutation in the GATA4 gene (600576), and ASD4 (611363), caused by mutation in the TBX20 gene (606061). ASD3 (614089) and ASD5 (612794), in which atrial septal defect is not associated with other cardiac abnormalities, are caused by mutation in the MYH6 (160710) and ACTC1 (102540) genes, respectively. ASD6 (613087), in which atrial septal defect may be associated with aneurysm of the interatrial septum and cardiac arrhythmias, is caused by mutation in the TLL1 gene (606742). ASD7 (108900), in which ASD is often associated with atrioventricular conduction defects, is caused by mutation in the NKX2-5 gene (600584). ASD8 (614433), in which ASD may be associated with other cardiac anomalies, is caused by mutation in the CITED2 gene (602937). ASD9 (614475) is caused by mutation in the GATA6 gene (601656). Somatic mutations in the HAND1 gene (602406) have been identified in tissue samples from patients with ASDs.
An abnormality related to a defect of vertebral separation of cervical vetebrae during development.
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
A flattened vertebral body shape with reduced distance beween the vertebral endplates affecting the thoracic spine.
A rare hereditary ataxia with characteristics of an apparently non-progressive or slowly progressive symmetrical ataxia of gait, pyramidal signs in the limbs, spasticity and hyperreflexia (especially in the lower limbs) together with dysarthria and impaired pupillary reaction to light, presenting as a fixed miosis. Nystagmus may also be present.
Distal arthrogryposis type 6 (DA6) is distinguished by the additional feature of sensorineural deafness (summary by Bamshad et al., 2009). For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120).
Distal arthrogryposis type 5 is distinguished from other forms of DA by the presence of ocular abnormalities, typically ptosis, ophthalmoplegia, and/or strabismus, in addition to contractures of the skeletal muscles. Some cases have been reported to have pulmonary hypertension as a result of restrictive lung disease (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA5 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 3 (DA3, or Gordon syndrome; 114300) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of cleft palate and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders might represent variable expressivity of the same condition. For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1A (108120). Genetic Heterogeneity of Distal Arthrogryposis 5 A subtype of DA5 due to mutation in the ECEL1 gene (605896) on chromosome 2q36 has been designated DA5D (615065). See NOMENCLATURE.
A reduced degree of voluntary and involuntary facial movements involved in responded to others or expressing emotions.
Absence of one or more interphalangeal creases (i.e., of the transverse lines in the skin between the phalanges of the fingers).
Hemangioma, a benign tumor of the vascular endothelial cells, occurring in the midline region of the face.
Familial hypobetalipoproteinemia (FHBL) is a disorder that impairs the body's ability to absorb and transport fats. This condition is characterized by low levels of a fat-like substance called cholesterol in the blood. The severity of signs and symptoms experienced by people with FHBL vary widely. The most mildly affected individuals have few problems with absorbing fats from the diet and no related signs and symptoms. Many individuals with FHBL develop an abnormal buildup of fats in the liver called hepatic steatosis or fatty liver. In more severely affected individuals, fatty liver may progress to chronic liver disease (cirrhosis). Individuals with severe FHBL have greater difficulty absorbing fats as well as fat-soluble vitamins such as vitamin E and vitamin A. This difficulty in fat absorption leads to excess fat in the feces (steatorrhea). In childhood, these digestive problems can result in an inability to grow or gain weight at the expected rate (failure to thrive).
The presence of a supernumerary, i.e. third, crus of the helix in the helix, arising at or above the normal bifurcation of the antihelix.
Familial anonychia/onychodystrophy with hypoplasia or absence of distal phalanges (ODP) is a rare disorder characterized by onychodystrophy, anonychia, brachydactyly of the fifth finger, and digitalization of the thumbs, with absence or hypoplasia of the distal phalanges of the hands and feet. Generally the nails of the first to third digits are progressively deformed with total anonychia in the last 2 digits and in all toes (summary by Genzer-Nir et al., 2010). A syndrome has been described in which affected females display juvenile hypertrophy of the breast (JHB; 113670) in association with ODP, whereas males have only ODP (mammary-digital-nail syndrome; 613689).
Spondyloarthropathy (SpA), one of the commonest chronic rheumatic diseases, includes a spectrum of related disorders comprising the prototype ankylosing spondylitis (AS), a subset of psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthropathy (Miceli-Richard et al., 2004). These phenotypes are difficult to differentiate because they may occur simultaneously or sequentially in the same patient. Studies have suggested that a predominant shared component, including HLA-B27, predisposes to all phenotypic subsets, and that these subsets should be considered as various phenotypic expressions of the same disease (Said-Nahal et al., 2000, Said-Nahal et al., 2001). Braun and Sieper (2007) provided a detailed review of ankylosing spondylitis, including clinical features, pathogenesis, and management. Genetic Heterogeneity of Susceptibility to Spondyloarthropathy Additional susceptibility loci for spondyloarthropathy have been identified on chromosome 9q31-q34 (SPDA2; 183840) and chromosome 2q36 (SPDA3; 613238).
Rupture of an intracranial aneurysm, an outpouching or sac-like widening of a cerebral artery, leads to a subarachnoid hemorrhage, a sudden-onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension, and excessive alcohol intake are associated with subarachnoid hemorrhage (summary by Krischek and Inoue, 2006). Genetic Heterogeneity of Intracranial Berry Aneurysm Intracranial berry aneurysm-1 (ANIB1) has been mapped to chromosome 7q11.2. Other mapped loci for intracranial berry aneurysm include ANIB2 (608542) on chromosome 19q13, ANIB3 (609122) on 1p36.13-p34.3, ANIB4 (610213) on 5p15.2-14.3, ANIB5 (300870) on Xp22, ANIB6 (611892) on 9p21, ANIB7 (612161) on 11q24-q25, ANIB8 (612162) on 14q23, ANIB9 (612586) on 2q, ANIB10 (612587) on 8q, and ANIB11 (614252) on 8p22.
A rare syndrome comprising hypocalcified-hypoplastic tooth enamel, onycholysis with subungual hyperkeratosis, and hypohidrosis.
Transient episodes of weakness of the arm, leg, and in some cases the face on one side of the body.
Intermittent episodes of paralysis of all four limbs.
Hereditary persistence of alpha-fetoprotein (HPAFP) is a clinically benign autosomal dominant condition characterized by continued expression of alpha-fetoprotein in adult life (summary by McVey et al., 1993).
Alpha-fetoprotein deficiency appears to be a benign genetic trait (Greenberg et al., 1992; Sharony et al., 2004).
Syndrome characterised by congenital permanent alopecia universalis, intellectual disability, psychomotor epilepsy and periodontal pyorrhoea. Total permanent alopecia and periodontal pyorrhoea are invariably concomitant while intellectual disability and psychomotor epilepsy are observed in most patients. No other abnormality of nails or skin (apart from absence of hair) has been reported. Transmission is autosomal dominant.
Autosomal dominant palmoplantar keratoderma with congenital alopecia (PPK-CA) is a rare genetic skin disorder characterized by absence of scalp and body hair and palmoplantar keratoderma, without other hand complications.
Alopecia areata is a genetically determined, immune-mediated disorder of the hair follicle with an estimated lifetime risk of approximately 2%, making it one of the most common human autoimmune diseases. It shows a spectrum of severity that ranges from patchy localized hair loss on the scalp to the complete absence of hair everywhere on the body (Gilhar and Kalish, 2006).
The presence of calcium deposition in the choroid plexus.
Congenital absence or closure of the opening of the lacrimal punctum.
Hypoglossia-hypodactyly syndrome is characterized by a hypoplastic mandible, absence of the lower incisors, hypoglossia, and a variable degree of absence of the digits and limbs. Intelligence is normal (Hall, 1971). Hall (1971) classified what he termed the 'syndromes of oromandibular and limb hypogenesis,' which comprised a range of disorders with hypoglossia in common. Type I included hypoglossia and aglossia in isolation. Type II included hypoglossia with hypomelia/hypodactylia. Type III included glossopalatine ankylosis with hypoglossia or hypoglossia and hypomelia/hypodactyly. Type IV included intraoral bands with fusion with hypoglossia or hypoglossia and hypomelia/hypodactyly. Type V included several syndromes, such as Hanhart syndrome, Pierre Robin syndrome (261800), Moebius syndrome (157900), and amniotic band syndrome (217100). Hall (1971) noted that complete aglossia or adactylia had not been reported, and suggested that 'hypoglossia-hypodactylia' is a more accurate term. See also hypoglossia and situs inversus (612776).
Adenosine deaminase (ADA) deficiency is a systemic purine metabolic disorder that primarily affects lymphocyte development, viability, and function. The clinical phenotypic spectrum includes: Severe combined immunodeficiency disease (SCID), often diagnosed by age six months and usually by age 12 months; Less severe ""delayed"" onset combined immune deficiency (CID), usually diagnosed between age one and ten years; ""Late/adult onset"" CID, diagnosed in the second to fourth decades; Benign ""partial ADA deficiency"" (very low or absent ADA activity in erythrocytes but greater ADA activity in nucleated cells), which is compatible with normal immune function. Infants with typical early-onset ADA-deficient SCID have failure to thrive and opportunistic infections associated with marked depletion of T, B, and NK lymphocytes, and an absence of both humoral and cellular immune function. If immune function is not restored, children with ADA-deficient SCID rarely survive beyond age one to two years. Infections in delayed- and late-onset types (commonly, recurrent otitis, sinusitis, and upper respiratory) may initially be less severe than those in individuals with ADA-deficient SCID; however, by the time of diagnosis these individuals often have chronic pulmonary insufficiency and may have autoimmune phenomena (cytopenias, anti-thyroid antibodies), allergies, and elevated serum concentration of IgE. The longer the disorder goes unrecognized, the more immune function deteriorates and the more likely are chronic sequelae of recurrent infection.
Absence of specific immunoglobulins directed against a specific antigen or microorganism.
Acropectorovertebral dysgenesis, or F syndrome, is an autosomal dominant skeletal dysplasia characterized by carpal and tarsal synostoses, syndactyly between the first and second fingers, hypodactyly and polydactyly of feet, and abnormalities of the sternum and spine (summary by Thiele et al., 2004).
Acromial dimples are skin depressions overlying the acromial process of the scapula. They are thought to arise from the entrapment of tissue between a bony structure and the uterine wall. The skin and bone become compressed and tethering results when the pressure is released. They are usually bilateral and are an isolated finding warranting no further investigation (summary by Liu and Nanan, 2008). Acromial dimples occur as a virtually consistent feature of 18q deletion (Insley, 1967).
An abnormal indentation of the skin in the region of the nasal tip.
Calvarial hyperostosis is a benign X-linked disorder that affects only the skull. Symptoms are prominent frontoparietal bones, flat nasal root, short upturned nose, high forehead with ridging of the metopic and sagittal sutures, and lateral frontal prominences. Radiographs of the skull show increased bone thickness at the sagittal suture line and prominent lateral frontal horns. Increased intracranial pressure and cranial nerve entrapment do not occur (summary by Borra et al., 2014).
A developmental defect characterized by the absence of the first metatarsal bone.
Any structural anomaly of the limbic system, a set of midline structures surrounding the brainstem of the mammalian brain, originally described anatomically, e.g., hippocampal formation, amygdala, hypothalamus, cingulate cortex. Although the original designation was anatomical, the limbic system has come to be associated with the system in the brain subserving emotional functions. As such, it is very poorly defined and doesn't correspond closely to the anatomical meaning any longer. [BirnLex].
An abnormality of head shape characterized by the presence of a short, wide head as well as a pointy or conical form of the top of the head owing to premature closure of the coronal and lambdoid sutures.
Increased width of the distal phalanx of thumb.
An abnormality of the C-shaped rings of hyaline cartilage, normally 16 to 20 in number, that occupy the anterior two-thirds of the circumference of the trachea (the posterior portion of the ring is completed by fibrous and smooth muscle tissue).
A hamartoma (a benign, focal malformation consisting of a disorganized mixture of cells and tissues) of the retina.
Autosomal Dominant Compelling Helioopthalmic Outburst (ACHOO) Syndrome is characterized by uncontrollable sneezing in response to the sudden exposure to bright light, typically intense sunlight. This type of sneezing is also known as photic sneezing. About one in four individuals who already have a prickling sensation in their nose will sneeze in response to sunlight, but “pure” photic sneezing is far less common. Sneezing is usually triggered by contact with infectious agents or after inhaling irritants, but the cause of photic sneezing is not fully understood. It may involve an over-excitability of the visual cortex in response to light, leading to a stronger activation of the secondary somatosensory areas.
A developmental defect resulting in the congenital absence of skin on the scalp in the parietal area.
A developmental defect resulting in the congenital absence of skin on the trunk or the limbs.
Autosomal recessive hypercholesterolemia is a rare monogenic disease characterized by very high levels of low-density lipoprotein (LDL) cholesterol (usually above 400 mg/dl) and increased risk of premature atherosclerotic cardiovascular disease (summary by Sanchez-Hernandez et al., 2018).
Hydroa vacciniforme (HV) is a rare photodermatosis characterized by acute vesiculation and crusting and scarring following sun exposure (Gupta et al., 1999).
Stargardt disease is the most common hereditary macular dystrophy and is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. STGD is most commonly inherited as an autosomal recessive trait (see 248200), but STGD4 is inherited as an autosomal domiant trait (summary by Kniazeva et al., 1999).
Substantial differences in cognitive abilities (e.g., visuospatial abilities, memory, vocabulary, semantics, and symbolic reasoning) tend to cluster within individuals. Model-fitting metaanalyses based on dozens of twin and adoption studies have estimated that approximately 50% of total population variance in intelligence can be attributed to genetic factors (Devlin et al., 1997). Heritability of quantitatively distributed traits such as intelligence is likely to be due to multiple genes of varying effect size, called quantitative trait loci (QTLs). QTLs for intelligence have been mapped to chromosome 4 (INTLQ1), chromosome 2q (INTLQ2; 610294), and chromosome 6p (INTLQ3; 610295).
Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support. The disease course varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s.
Verloes et al. (1992) described a rare variant of frontonasal dysplasia (see FND1, 136760), designated acromelic frontonasal dysplasia (AFND), in which similar craniofacial anomalies are associated with variable central nervous system malformations and limb defects including tibial hypoplasia/aplasia, talipes equinovarus, and preaxial polydactyly of the feet.
The common blue nevus of Jadassohn-Tieche most frequently presents as a solitary blue 1- to 10-mm dome-shaped papule on the dorsal hand or foot. It is characterized by greatly elongated wavy groups of spindled dermal melanocytes that are oriented parallel to the epidermis. Cellular blue nevi resemble common blue nevi clinically but are usually larger, ranging from 1 to 3 cm in diameter, and occur primarily on the buttocks or sacrum as a solitary blue nodule (summary by Knoell et al., 1998).
A unilateral vestibular Schwannoma (acoustic neurinoma).
Xanthinuria type II is an autosomal recessive inborn error of metabolism resulting from a defect in the synthesis of the molybdenum cofactor, which is necessary for the 2 enzymes that degrade xanthine: XDH (607633) and AOX1 (602841). Most individuals with type II xanthinuria are asymptomatic, but some develop urinary tract calculi, acute renal failure, or myositis due to tissue deposition of xanthine. Laboratory studies show increased serum and urinary hypoxanthine and xanthine and decreased serum and urinary uric acid (summary by Ichida et al., 2001). Two clinically similar but distinct forms of xanthinuria are recognized. In type I xanthinuria (XAN1; 278300), there is an isolated deficiency of xanthine dehydrogenase resulting from mutation in the XDH gene; in type II, there is a dual deficiency of xanthine dehydrogenase and aldehyde oxidase. Type I patients can metabolize allopurinol, whereas type II patients cannot (Simmonds et al., 1995).
Hereditary spastic paraplegia 8 (SPG8) is a pure hereditary spastic paraplegia characterized by slowly progressive spastic paraplegia of the lower limbs (i.e., hyperreflexia and clonus) with onset between ages 18 and 59 years (average: 37.2 years in one study). Other findings can include weakness with muscle wasting of the lower limbs, urinary urgency, and decreased vibration sense. Affected individuals often become wheelchair dependent.
A severe form of B lymphocytopenia in which the count of B cells is very low or absent. [HPO:probinson]
Spondyloepimetaphyseal dysplasia with joint laxity type 2 (SEMDJL2) is characterized by short stature, distinctive midface retrusion, progressive knee malalignment (genu valgum and/or varum), generalized ligamentous laxity, and mild spinal deformity. Intellectual development is not impaired. Radiographic characteristics include significantly retarded epiphyseal ossification that evolves into epiphyseal dysplasia and precocious osteoarthritis, metaphyseal irregularities and vertical striations, constricted femoral neck, slender metacarpals and metatarsals, and mild thoracolumbar kyphosis or scoliosis with normal or mild platyspondyly (summary by Min et al., 2011). For a discussion of genetic heterogeneity of SEMD with joint laxity, see SEMDJL1 (271640).
Narrowing (becoming gradually narrower) of the distance between vertebral pedicles that gets progressively more severe towards to caudal (lower) end of the vertebral column. Note that normally, the interpedicular distances get progressively wider as one proceeds down the spine.
An abnormally reduced diameter of the femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Underdevelopment of one or more carpal bones.
Increased size of the vestibular aqueduct.
Neuronal intranuclear inclusion disease (NIID) is characterized pathologically by eosinophilic intranuclear inclusions in neurons of the peripheral, central, and autonomic nervous systems associated with varying degrees of neuronal loss. Symptoms usually begin in childhood but adult-onset cases have also been described. Clinical expression is variable, depending on the sites of maximal neuronal loss, but is usually a multisystem degenerative process of the central nervous system or a visceral neuropathy (summary by Kimber et al., 1998). See the neuronal form of intestinal pseudoobstruction (243180).
A rare developmental defect during embryogenesis with a typically unilateral, partial or full-thickness, variably sized defect of the superior eyelid, ranging from a small notch to complete absence of the entire lid, which is commonly triangular in shape (with base at eyelid margin) and located on the medial third of the lid. It can occur isolated, associated with other anomalies (e.g. ocular/orbital and facial), or as part of a syndrome.
Bosma arhinia microphthalmia syndrome (BAMS) is characterized by severe hypoplasia of the nose and eyes, palatal abnormalities, deficient taste and smell, inguinal hernias, hypogonadotropic hypogonadism with cryptorchidism, and normal intelligence (summary by Graham and Lee, 2006). Also see absence of nasal bones (161480).
Graves disease is a condition that affects the function of the thyroid, which is a butterfly-shaped gland in the lower neck. The thyroid makes hormones that help regulate a wide variety of critical body functions. For example, thyroid hormones influence growth and development, body temperature, heart rate, menstrual cycles, and weight. In people with Graves disease, the thyroid is overactive and makes more hormones than the body needs. The condition usually appears in mid-adulthood, although it may occur at any age.Excess thyroid hormones can cause a variety of signs and symptoms. These include nervousness or anxiety, extreme tiredness (fatigue), a rapid and irregular heartbeat, hand tremors, frequent bowel movements or diarrhea, increased sweating and difficulty tolerating hot conditions, trouble sleeping, and weight loss in spite of an increased appetite. Affected women may have menstrual irregularities, such as an unusually light menstrual flow and infrequent periods. Some people with Graves disease develop an enlargement of the thyroid called a goiter. Depending on its size, the enlarged thyroid can cause the neck to look swollen and may interfere with breathing and swallowing.Between 25 and 50 percent of people with Graves disease have eye abnormalities, which are known as Graves ophthalmopathy. These eye problems can include swelling and inflammation, redness, dryness, puffy eyelids, and a gritty sensation like having sand or dirt in the eyes. Some people develop bulging of the eyes caused by inflammation of tissues behind the eyeball and ""pulling back"" (retraction) of the eyelids. Rarely, affected individuals have more serious eye problems, such as pain, double vision, and pinching (compression) of the optic nerve connecting the eye and the brain, which can cause vision loss.A small percentage of people with Graves disease develop a skin abnormality called pretibial myxedema or Graves dermopathy. This abnormality causes the skin on the front of the lower legs and the tops of the feet to become thick, lumpy, and red. It is not usually painful.
Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome is characterized by megalencephaly, polymicrogyria, and hydrocephalus with variable polydactyly. It has been described in six unrelated patients. Intellectual deficit or slow development is also present. The mode of inheritance of this syndrome is unknown since all cases were sporadic.
The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. One peculiar form of thyroid tumors is characterized by the presence of cell oxyphilia. Oxophil cells are found in a minority of thyroid tumors, either benign or malignant. These cells show a large volume of granular eosinophilic cytoplasm and are very rich in mitochondria. The familial occurrence of thyroid tumors with cell oxyphilia was reported by Katoh et al. (1998). Canzian et al. (1998) reported such a family with affected members in 3 generations and by linkage analysis mapped the gene to 19p13. For general phenotypic information and a discussion of genetic heterogeneity of NMTC, see 188550.
Some degree of stimulation of the thyroid gland by chorionic gonadotropin (see 118860) is common during early pregnancy. When serum chorionic gonadotropin concentrations are abnormally high, e.g., in women with molar pregnancies (231090), overt hyperthyroidism may ensue. The pathophysiologic mechanism appears to be promiscuous stimulation of the thyrotropin receptor by the excess chorionic gonadotropin. The explanation for this stimulation is the close structural relations between chorionic gonadotropin and thyrotropin and between their receptors (Grossmann et al., 1997).
GRACILE syndrome is a severe disorder that begins before birth. GRACILE stands for the condition's characteristic features: growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death.In GRACILE syndrome, growth before birth is slow (intrauterine growth retardation). Affected newborns are smaller than average and have an inability to grow and gain weight at the expected rate (failure to thrive). A characteristic of GRACILE syndrome is excess iron in the liver, which likely begins before birth. Iron levels may begin to improve after birth, although they typically remain elevated. Within the first day of life, infants with GRACILE syndrome have a buildup of a chemical called lactic acid in the body (lactic acidosis). They also have kidney problems that lead to an excess of molecules called amino acids in the urine (aminoaciduria). Babies with GRACILE syndrome have cholestasis, which is a reduced ability to produce and release a digestive fluid called bile. Cholestasis leads to irreversible liver disease (cirrhosis) in the first few months of life.Because of the severe health problems caused by GRACILE syndrome, infants with this condition do not survive for more than a few months, and about half die within a few days of birth.
Focal proliferation of glial cells in the basal ganglia.
Meckel syndrome is a rare autosomal recessive lethal condition characterized by an occipital meningoencephalocele, enlarged kidneys with multicystic dysplasia and fibrotic changes in the portal area of the liver and with ductal proliferation, and postaxial polydactyly. For a more complete phenotypic description and information on genetic heterogeneity, see MKS1 (249000).
Elevations of the levels of SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) that occur during infections.
A very rare condition with characteristics of craniosynostosis and clavicular hypoplasia, delayed closure of the fontanelle, anal anomalies, genitourinary malformations and skin eruptions. It has been described in seven patients from four unrelated families. Cranial abnormalities include a coronal synostosis with wide-open anterior and posterior fontanelles and large parietal foramina. In some patients the skin eruption has been classified as porokeratosis. Sensorineural hearing loss and mild to severe developmental delay are common. The condition is transmitted as an autosomal recessive trait.
Age-related macular degeneration (ARMD) is a progressive degeneration of photoreceptors and underlying retinal pigment epithelium (RPE) cells in the macula region of the retina. It is a highly prevalent disease and a major cause of blindness in the Western world. Drusen, pale excrescences of variable size, and other deposits accumulate below the RPE on the Bruch membrane; clinical and histopathologic investigations have shown that these extracellular deposits are the hallmark of early ARMD. As ARMD advances, areas of geographic atrophy of the RPE can cause visual loss, or choroidal neovascularization can occur to cause wet, or exudative, ARMD with accompanying central visual loss (summary by De et al., 2007). Genetic Heterogeneity of Age-Related Macular Degeneration ARMD2 (153800) is associated with mutation in the ABCR gene (601691) on chromosome 1p, and ARMD3 (608895) is caused by mutation in the FBLN5 gene (604580) on chromosome 14q31. Up to 50% of the attributable risk of age-related macular degeneration (ARMD4; 610698) appears to be explained by a polymorphism in the CFH gene (134370.0008). ARMD5 (613761) and ARMD6 (613757) are associated with mutation in the ERCC6 (609413) and RAX2 (610362) genes, respectively. ARMD7 (610149) and ARMD8 (613778), which both represent susceptibility linked to chromosome 10q26, are associated with single-nucleotide polymorphisms in the HTRA1 (602194) and ARMS2 (611313) genes, respectively. ARMD9 (611378) is associated with single-nucleotide polymorphisms in the C3 gene (120700). ARMD10 (611488) maps to chromosome 9q32 and may be associated with a polymorphism in the TLR4 gene (603030). ARMD11 (611953) is association with variation in the CST3 gene (604312); ARMD12 (613784) with variation in the CX3CR1 gene (601470); and ARMD13 (615439) with variation in the CFI gene (217030). ARMD14 (615489) is associated with variation in or near the C2 (613927) and CFB (138470) genes on chromosome 6p21. ARMD15 (615591) is associated with variation in the C9 gene (120940). There is evidence for a form of ARMD caused by mutation in the mitochondrial gene MTTL1 (590050). A haplotype carrying deletion of the complement factor H-related genes CFHR1 (134371) and CFHR3 (605336) is also associated with reduced risk of ARMD. Lotery and Trump (2007) reviewed the molecular biology of age-related macular degeneration and tabulated the genes associated with ARMD, including those with only positive findings versus genes for which conflicting results have been found.
An abnormal prolongation of the miniature endplate potentials, i.e. the postsynaptic response to transmitter released from an individual vesicle at the neuromuscular junction.
Relatively increased growth of the fibula compared to that of the tibia.
The Maroteaux type of mesomelic sysplasia is an autosomal recessive disorder characterized by severe dwarfism (height below 120 cm) with shortening of the middle and distal segments of the limbs. This condition is usually diagnosed at birth and becomes more obvious in the first 2 years of life. X-rays show short broad fingers, square flat feet, and shortening of the long bones (particularly the forearms). The radius is bowed; the ulna is shorter than the radius, and its distal end is occasionally hypoplastic. The skull is dolichocephalic and a shortness of the trunk, with decreased vertebral height and narrowing of the lumbar interpedicular distances, is consistently observed. Facial appearance and intelligence are normal (summary by Faivre et al., 2000).
Over curvature of the lower thoracic region, leading to a round back or if sever to a hump.
A reduction of the distance between thoracolumbar vertebral pedicles.
Premature chromatid separation consists of separate and splayed chromatids with discernible centromeres and involves all or most chromosomes of a metaphase. It is found in up to 2% of metaphases in cultured lymphocytes from approximately 40% of normal individuals. When PCS is present in 5% or more of cells, it is known as the 'heterozygous PCS trait' and has no obvious phenotypic effect, although some have reported decreased fertility (Gabarron et al., 1986). Inheritance is autosomal codominant (Kajii and Ikeuchi, 2004). See also 158250 for a possible inherited predisposition to nondisjunction, which may be a related phenomenon.
Muenke syndrome is defined by the presence of the specific FGFR3 pathogenic variant – c.749C>G – that results in the protein change p.Pro250Arg. Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pan synostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (reduced anteroposterior dimension of the skull), although turribrachycephaly (a ""tower-shaped"" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: temporal bossing; widely spaced eyes, ptosis or proptosis (usually mild); midface retrusion (usually mild); and highly arched palate or cleft lip and palate. Strabismus is common. Other findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); epilepsy; intracranial anomalies; intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family. Of note, some individuals who have the p.Pro250Arg pathogenic variant may have no signs of Muenke syndrome on physical or radiographic examination.
The histiocytosis-lymphadenopathy plus syndrome comprises features of 4 histiocytic disorders previously thought to be distinct: Faisalabad histiocytosis (FHC), sinus histiocytosis with massive lymphadenopathy (SHML), H syndrome, and pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome (PHID). FHC described an autosomal recessive disease involving joint deformities, sensorineural hearing loss, and subsequent development of generalized lymphadenopathy and swellings in the eyelids that contain histiocytes (summary by Morgan et al., 2010). SHML, or familial Rosai-Dorfman disease, was described as a rare cause of lymph node enlargement in children, consisting of chronic massive enlargement of cervical lymph nodes frequently accompanied by fever, leukocytosis, elevated erythrocyte sedimentation rate, and polyclonal hypergammaglobulinemia. Extranodal sites were involved in approximately 25% of patients, including salivary glands, orbit, eyelid, spleen, and testes. The involvement of retropharyngeal lymphoid tissue sometimes caused snoring and sleep apnea (summary by Kismet et al., 2005). H syndrome was characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism; hearing loss was also found in about half of patients, and many had short stature. PHID was characterized by predominantly antibody-negative insulin-dependent diabetes mellitus associated with pigmented hypertrichosis and variable occurrence of other features of H syndrome, with hepatosplenomegaly occurring in about half of patients (Cliffe et al., 2009). Bolze et al. (2012) noted that mutations in the SLC29A3 gene (612373) had been implicated in H syndrome, PHID, FHC, and SHML, and that some patients presented a combination of features from 2 or more of these syndromes, leading to the suggestion that these phenotypes should be grouped together as 'SLC29A3 disorder.' Bolze et al. (2012) suggested that the histologic features of the lesions seemed to be the most uniform phenotype in these patients. In addition, the immunophenotype of infiltrating cells in H syndrome patients was shown to be the same as that seen in patients with the familial form of Rosai-Dorfman disease, further supporting the relationship between these disorders (Avitan-Hersh et al., 2011; Colmenero et al., 2012).
Mutations in the PITX3 gene have been found to cause multiple types of cataract, which have been described as congenital total and posterior polar. The preferred title/symbol for this entry was formerly 'Cataract, Posterior Polar, 4; CTPP4.'
A type of posterior subcapsular cataract characterized by an iridescent color.
Atrophy (wasting) affecting primary type 2 muscle fibers. This feature in general can only be observed on muscle biopsy.
Absence of hair in the anterior midline and/or parietal areas.
Mandibulofacial dysostosis with microcephaly (MFDM) is characterized by malar and mandibular hypoplasia; microcephaly (congenital or postnatal onset); malformations of the pinna, auditory canal, and/or middle ear (ossicles and semi-circular canals) with associated conductive hearing loss; and distinctive facial features (metopic ridge, up- or downslanting palpebral fissures, prominent glabella, broad nasal bridge, bulbous nasal tip, and everted lower lip). Associated craniofacial malformations may include cleft palate, choanal atresia, and facial asymmetry. Intellectual disability is a prominent feature. Major extracranial malformations include: esophageal atresia (~40%), congenital heart disease (~40%), and thumb abnormalities (~25%). Short stature is present in approximately one third of individuals.
Hypomyelination and congenital cataract (HCC) is usually characterized by bilateral congenital cataracts and normal psychomotor development in the first year of life, followed by slowly progressive neurologic impairment manifest as ataxia, spasticity (brisk tendon reflexes and bilateral extensor plantar responses), and mild to moderate cognitive impairment. Dysarthria and truncal hypotonia are observed. Cerebellar signs (truncal titubation and intention tremor) and peripheral neuropathy (muscle weakness and wasting of the legs) are present in the majority of affected individuals. Seizures can occur. In a few cases cataracts may be absent.
Progressive external ophthalmoplegia-4 is an autosomal dominant form of mitochondrial disease that variably affects skeletal muscle, the nervous system, the liver, and the gastrointestinal tract. Age at onset ranges from infancy to adulthood. The phenotype ranges from relatively mild, with adult-onset skeletal muscle weakness and weakness of the external eye muscles, to severe, with a multisystem disorder characterized by delayed psychomotor development, lactic acidosis, constipation, and liver involvement (summary by Young et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640).
CLN10 disease is a severe disorder that primarily affects the nervous system. Individuals with this condition typically show signs and symptoms soon after birth. These signs and symptoms can include muscle rigidity, respiratory failure, and prolonged episodes of seizure activity that last several minutes (status epilepticus). It is likely that some affected individuals also have seizures before birth while in the womb. Infants with CLN10 disease have unusually small heads (microcephaly) with brains that may be less than half the normal size. There is a loss of brain cells in areas that coordinate movement (the cerebellum) and control thinking and emotions (the cerebral cortex). Nerve cells in the brain also lack a fatty substance called myelin, which protects them and promotes efficient transmission of nerve impulses. Infants with CLN10 disease often die hours to weeks after birth.In some individuals with CLN10 disease, the condition does not appear until later in life, between late infancy and adulthood. These individuals have a gradual loss of brain cells and often develop problems with balance and coordination (ataxia), loss of speech, a progressive loss in intellectual functioning (cognitive decline), and vision loss. Individuals with later-onset CLN10 disease have a shortened lifespan, depending on when their signs and symptoms first started.CLN10 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs). All of these disorders affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation ""CLN,"" meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype.
Reduced strength of the musculature of the distal extremities.
The term dystrophy means abnormal growth. However, muscular dystrophy is used to describe primary myopathies with a genetic basis and a progressive course characterized by progressive skeletal muscle weakness and wasting, defects in muscle proteins, and histological features of muscle fiber degeneration (necrosis) and regeneration. If possible, it is preferred to use other HPO terms to describe the precise phenotypic abnormalities.
Wasting of thenar muscles, which are located on palm of the hand at the base of the thumb.
Atrophy of the intrinsic muscle groups of the hand, comprising the thenar and hypothenar muscles; the interossei muscles; and the lumbrical muscles.
PNPOD is an autosomal recessive inborn error of metabolism resulting in vitamin B6 deficiency that manifests as neonatal-onset severe seizures and subsequent encephalopathy. Patients with PNPO mutations tend to respond better to treatment with pyridoxal 5-prime phosphate (PLP) than with pyridoxine (summary by Plecko et al., 2014).
Opioid addiction is a long-lasting (chronic) disease that can cause major health, social, and economic problems. Opioids are a class of drugs that act in the nervous system to produce feelings of pleasure and pain relief. Some opioids are legally prescribed by healthcare providers to manage severe and chronic pain. Commonly prescribed opioids include oxycodone, fentanyl, buprenorphine, methadone, oxymorphone, hydrocodone, codeine, and morphine. Some other opioids, such as heroin, are illegal drugs of abuse.Opioid addiction is characterized by a powerful, compulsive urge to use opioid drugs, even when they are no longer required medically. Opioids have a high potential for causing addiction in some people, even when the medications are prescribed appropriately and taken as directed. Many prescription opioids are misused or diverted to others. Individuals who become addicted may prioritize getting and using these drugs over other activities in their lives, often negatively impacting their professional and personal relationships. It is unknown why some people are more likely to become addicted than others.Opioids change the chemistry of the brain and lead to drug tolerance, which means that over time the dose needs to be increased to achieve the same effect. Taking opioids over a long period of time produces dependence, such that when people stop taking the drug, they have physical and psychological symptoms of withdrawal (such as muscle cramping, diarrhea, and anxiety). Dependence is not the same thing as addiction; although everyone who takes opioids for an extended period will become dependent, only a small percentage also experience the compulsive, continuing need for the drug that characterizes addiction.Opioid addiction can cause life-threatening health problems, including the risk of overdose. Overdose occurs when high doses of opioids cause breathing to slow or stop, leading to unconsciousness and death if the overdose is not treated immediately. Both legal and illegal opioids carry a risk of overdose if a person takes too much of the drug, or if opioids are combined with other drugs (particularly tranquilizers called benzodiazepines).
Congenital stromal corneal dystrophy is characterized by the presence of bilateral corneal opacities that can be seen at or shortly after birth. The surface of the cornea is normal or slightly irregular; small opacities are seen throughout the stroma of the entire cornea and give the cornea a cloudy appearance. Strabismus is common. Nystagmus is uncommon. Amblyopia can develop in children.
Abnormality of the dens of the axis, which is also known as the odontoid process.
Pectus carinatum affecting primarily the superior part of the sternum.
Pectus excavatum (defect of the chest wall characterized by depression of the sternum) affecting primarily the inferior region of the sternum.
Trichilemmal cysts, also known as pilar cysts or tricholemmal cysts, are derived from the outer root sheath of the deeper parts of a hair follicle and consist of a well-keratinized epidermal wall surrounding semisolid hair keratin. They occur predominantly on the scalp, are easily enucleated, and appear as a firm, smooth, white-walled cyst without a punctum (McGavran and Binnington, 1966; Pinkus, 1969; Leppard and Sanderson, 1976).
Frias syndrome is characterized by mild exophthalmia, palpebral ptosis, hypertelorism, short square hands with minimal proximal syndactyly between the second and third fingers, small broad great toes, and short stature. Some patients may exhibit bilateral pedunculated postminimi (summary by Martinez-Fernandez et al., 2014).
Primary pigmented micronodular adrenocortical disease is a form of ACTH-independent adrenal hyperplasia resulting in Cushing syndrome. It is usually seen as a manifestation of the Carney complex (CNC1; 160980), a multiple neoplasia syndrome. However, PPNAD can also occur in isolation (Groussin et al., 2002). Genetic Heterogeneity of Primary Pigmented Micronodular Adrenocortical Disease See also PPNAD2 (610475), caused by mutation in the PDE11A gene (604961) on chromosome 2q31; PPNAD3 (614190), caused by mutation in the PDE8B gene (603390) on chromosome 5q13; and PPNAD4 (615830), caused by a duplication on chromosome 19p13 that includes the PRKACA gene (601639).
Increased top to bottom height of vertebral bodies.
Buruli ulcer is an infectious disease prevalent in many tropical and subtropical regions caused by infection with Mycobacterium ulcerans. It is the third most frequent mycobacterial disease in humans worldwide, after tuberculosis (607948) and leprosy (246300). Lesions are most common on exposed parts of the body, especially the limbs. Buruli ulcer derives its name from a county in Uganda, East Africa, north of Kampala, where the disease was found in the late 1950s in hundreds of people living near marshes and riverine areas near the Nile River (Clancey et al., 1961; Barker, 1971). The disease was first described in the medical literature in 1948 in a report on patients in Australia (MacCallum et al., 1948). Patients have also been reported from tropical areas in Latin America and Asia (Stienstra et al., 2006; van der Werf et al., 2005).
The KANSL1-related intellectual disability syndrome is characterized by developmental delay/intellectual disability, neonatal/childhood hypotonia, dysmorphisms, congenital malformations, and behavioral features. Global psychomotor developmental delay is noted in all individuals from an early age. The majority of individuals with the KANSL1-related intellectual disability syndrome function in the mild to moderate range of intellectual disability. Other findings include epilepsy (55%), congenital heart defects (39%), renal and urologic anomalies (37%), and cryptorchidism (71% of males). Behavior in most is described as friendly, amiable, and cooperative.
Spondyloepiphyseal dysplasia of the Genevieve type (SEMDG) is characterized by infantile-onset severe developmental delay and skeletal dysplasia, including short stature, premature carpal ossification, platyspondyly, longitudinal metaphyseal striations, and small epiphyses (summary by van Karnebeek et al., 2016).
Testicular microlithiasis, the deposition of calcium phosphate microliths within the seminiferous tubules, has a population prevalence of 0.6 to 9% (Kim et al., 2003). Middleton et al. (2002) found that it was associated with a majority of primary testicular malignancies. Miller and Sidhu (2002) found that it was present in 1% of male idiopathic infertility cases.
HBV is a DNA virus that enters the liver via the bloodstream, and replication occurs only in liver tissue. Transmission occurs by percutaneous or mucosal exposure to infected blood or other body fluids. Approximately one third of all cases of cirrhosis and half of all cases of hepatocellular carcinoma (HCC; 114550) can be attributed to chronic HBV infection. Worldwide, 2 billion people have been infected with HBV, 360 million have chronic infection, and 600,000 die each year from HBV-related liver disease or HCC. However, there is marked geographic variability in HBV prevalence, with chronic infection affecting less than 2% of the populations of North America and western and northern Europe; between 2 and 7% of the populations of eastern and central Europe, the Amazon basin, the Middle East, and the Indian subcontinent; and more than 8% of the populations of Asia, sub-Saharan Africa, and the Pacific (Seeff and Hoofnagle, 2006; Shepard et al., 2006).
An increased concentration of insulin combined with a decreased concentration of glucose in the blood.
A form of diazoxide-sensitive diffuse hyperinsulinism characterised by episodes of hypoglycaemia induced by exercise due to an inappropriate lactate and pyruvate sensitivity in pancreatic beta-cells. Patients present with recurring episodes of hypoglycaemia associated with elevated insulin levels, within 30 minutes of a short period of anaerobic exercise. The degree of hypoglycaemia associated with exercise is variable and is only partially responsive to diazoxide. Mutations in the promoter element of SLC16A1 leads to an inappropriate presence of monocarboxylic acid transporter 1(MCT1). Mutations of the promoter region of SLC16A1 that permit gene expression in pancreatic beta-cells identified to date are dominant.
Mutations in the FYCO1 gene have been identified in families with autosomal recessive cataract described as congenital and congenital nuclear. The preferred title/symbol of this entry was formerly 'Cataract, Autosomal Recessive Congenital 2; CATC2.'
Congenital glutamine deficiency is a severe autosomal recessive disorder characterized by onset at birth of encephalopathy, lack of normal development, seizures, and hypotonia associated with variable brain abnormalities (summary by Haberle et al., 2011).
2-Methylbutyryl-CoA dehydrogenase (MBD) deficiency is an autosomal recessive metabolic disorder of impaired isoleucine degradation. It is most often ascertained via newborn screening and is usually clinically asymptomatic, although some patients have been reported to have delayed development and neurologic signs. Therefore, the clinical relevance of the deficiency is unclear (Sass et al.., 2008).
Immunodeficiency-54 is an autosomal recessive primary immunodeficiency characterized by severe intra- and extrauterine growth retardation, microcephaly, decreased numbers of natural killer (NK) cells, and recurrent viral infections, most often affecting the respiratory tract and leading to respiratory failure. Affected individuals also have adrenal insufficiency requiring corticosteroid replacement therapy and may have an increased susceptibility to cancer. Laboratory studies of patient cells showed a DNA repair defect (summary by Gineau et al., 2012).
An increased concentration of insulin in the blood in the fasting state, i.e., not as the response to food intake.
Majeed syndrome is characterized by: Chronic recurrent multifocal osteomyelitis (CRMO) that is of early onset with a lifelong course; and Congenital dyserythropoietic anemia (CDA) that presents as hypochromic, microcytic anemia during the first year of life and ranges from mild to transfusion dependent. Some individuals also develop a transient inflammatory dermatosis, often manifesting as Sweet syndrome (neutrophilic skin infiltration).
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Short QT syndrome is a cardiac channelopathy associated with a predisposition to atrial fibrillation and sudden cardiac death. Patients have a structurally normal heart, but electrocardiography (ECG) exhibits abbreviated QTc (Bazett's corrected QT) intervals of less than 360 ms (summary by Moreno et al., 2015). For a discussion of genetic heterogeneity of short QT syndrome, see SQT1 (609620).
Short QT syndrome is a cardiac channelopathy associated with a predisposition to atrial fibrillation and sudden cardiac death. Patients have a structurally normal heart, but electrocardiography (ECG) exhibits abbreviated QTc (Bazett's corrected QT) intervals of less than 360 ms (summary by Moreno et al., 2015). Genetic Heterogeneity of Short QT Syndrome Short QT syndrome-2 (SQT2; 609621) is caused by mutation in the KCNQ1 gene (607542). SQT3 (609622) is caused by mutation in the KCNJ2 gene (600681).
Underdevelopment of the pubis, which together with the ilium and the ischium, is one of the three bones that make up the hip bone.
Abnormally large size of the metaphyseal epiphyses.
Abnormally large size of the epiphyses of the phalanges of the fingers with respect to age-dependent norms.
Cone-shaped epiphyses (also known as coned epiphyses) are epiphyses that invaginate into cupped metaphyses. That is, the epiphysis has a cone-shaped distal extension resulting from increased growth of the central portion of the epiphysis relative to its periphery.
Visible increase in width of the non-hallux digit without an increase in the dorso-ventral dimension.
Enlarged parietal foramina are characteristic symmetric, paired radiolucencies of the parietal bones, located close to the intersection of the sagittal and lambdoid sutures, caused by deficient ossification around the parietal notch, which is normally obliterated by the fifth month of fetal development. Enlarged parietal foramina are usually asymptomatic. Meningeal, cortical, and vascular malformations of the posterior fossa occasionally accompany the bone defects and may predispose to epilepsy. In a minority of individuals, headaches, vomiting, or intense local pain are sometimes associated with the defects, especially on application of mild pressure to the unprotected cerebral cortex.
An abnormal appearance of the midbrain in axial magnetic resonance imaging in which the elongated superior cerebellar peduncles give the midbrain an appearance reminiscent of a molar or wisdom tooth.
Irregularity of the normally smooth surface of the metaphysis at the proximal end of the humerus (at the shoulder).
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065). CDG Ib is clinically distinct from most other CDGs by the lack of significant central nervous system involvement. The predominant symptoms are chronic diarrhea with failure to thrive and protein-losing enteropathy with coagulopathy. Some patients develop hepatic fibrosis. CDG Ib is also different from other CDGs in that it can be treated effectively with oral mannose supplementation, but can be fatal if untreated (Marquardt and Denecke, 2003). Thus, CDG Ib should be considered in the differential diagnosis of patients with unexplained hypoglycemia, chronic diarrhea, liver disease, or coagulopathy in order to allow early diagnosis and effective therapy (Vuillaumier-Barrot et al., 2002) Freeze and Aebi (1999) reviewed CDG Ib and CDG Ic (603147). Marques-da-Silva et al. (2017) systematically reviewed the literature concerning liver involvement in CDG.
A very rare disorder with characteristics of intrauterine growth retardation, under-ossification of the skull with large fontanelles, short limbs with absent phalanges and finger and toe syndactyly. Only 4 cases have been reported in the literature in 3 unrelated families. Dysmorphic features include narrow face with small palpebral fissures, small pointed nose, microstomia, micrognathia and low-set and posteriorly rotated ears. A posterior encephalocele and other congenital malformations can be observed. Prognosis is poor.
Shohat-type spondyloepimetaphyseal dysplasia (SEMDSH) is a chondrodysplasia characterized by vertebral, epiphyseal, and metaphyseal abnormalities, including scoliosis with vertebral compression fractures, flattened vertebral bodies, and hypomineralization of long bones. Affected individuals may exhibit a small trunk, short neck, small limbs, joint laxity, bowlegs, and/or abdominal distention with hepatosplenomegaly (summary by Egunsola et al., 2017).
The rib cage has the shape of a wide mouthed bell. That is, the superior portion of the rib cage is constricted, follwed by a convex region, and the inferior portion of the rib cage expands again to have a large diameter.
Megaconial-type congenital muscular dystrophy is an autosomal recessive disorder characterized by early-onset muscle wasting and mental retardation. Some patients develop fatal cardiomyopathy. Muscle biopsy shows peculiar enlarged mitochondria that are prevalent toward the periphery of the fibers but are sparse in the center (summary by Mitsuhashi et al., 2011).
Hystrix-like ichthyosis with deafness (HID) is a disorder characterized by dry, scaly skin (ichthyosis) and hearing loss that is usually profound. Hystrix-like means resembling a porcupine; in this type of ichthyosis, the scales may be thick and spiky, giving the appearance of porcupine quills.Newborns with HID typically develop reddened skin. The skin abnormalities worsen over time, and the ichthyosis eventually covers most of the body, although the palms of the hands and soles of the feet are usually only mildly affected. Breaks in the skin may occur and in severe cases can lead to life-threatening infections. Affected individuals have an increased risk of developing a type of skin cancer called squamous cell carcinoma, which can also affect mucous membranes such as the inner lining of the mouth. People with HID may also have patchy hair loss caused by scarring on particular areas of skin.
Reduced depth of the orbits associated with prominent-appearing ocular globes.
Abnormal increase in width of the distal region of the metacarpal bones.
Grange syndrome is a rare condition that primarily affects the blood vessels. It is characterized by narrowing (stenosis) or blockage (occlusion) of arteries that supply blood to various organs and tissues, including the kidneys, brain, and heart. Stenosis or occlusion of the arteries that supply blood to the kidneys (renal arteries) can result in chronic high blood pressure (hypertension). Blockage of the arteries that carry blood to the brain (cerebral arteries) can cause a stroke.Additional features of Grange syndrome can include short fingers and toes (brachydactyly), fusion of some of the fingers or toes (syndactyly), fragile bones that are prone to breakage, and learning disabilities. Most people with this disorder also have heart defects that are present from birth.
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal (or neonatal) forms of Bartter syndrome typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome (see BARTS3, 607364) present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Complete and diffuse scarring of glomerulus.
Abnormally increased production of urine by the fetus resulting in polyhydramnios.
PIK3CA-associated segmental overgrowth includes disorders of brain (e.g., MCAP [megalencephaly-capillary malformation] syndrome, hemimegalencephaly); and segmental body overgrowth (e.g., CLOVES [congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies] syndrome, fibroadipose hyperplasia [FH]). Heterozygous (usually somatic mosaic) pathogenic variants of PIK3CA are causative. MCAP syndrome is characterized by the major findings of (1) megalencephaly (MEG) or hemimegalencephaly (HMEG) associated with neurologic findings of hypotonia, seizures, and mild to severe intellectual disability; and (2) cutaneous capillary malformations with focal or generalized somatic overgrowth. Additional findings can include digital anomalies (syndactyly, polydactyly), cortical malformations – most distinctively polymicrogyria (PMG); and variable connective tissue dysplasia. CLOVES (or CLOVE) syndrome and fibroadipose hyperplasia (FH) may be associated with (1) MEG or HMEG; and (2) patchy segmental overgrowth associated with skeletal anomalies, lipomatosis, vascular malformations, and epidermal nevi.
A condition in which the superior portion of the helix is folded over to a greater degree than normal.
Impairment in the physical production of speech sounds.
An anomaly of the temporomandibular joint.
Transient blurring of vision associated with the aura phase of migraine.
Ossification of the posterior longitudinal ligament of the spine (OPLL) is a common degenerative spinal disorder that causes severe neurologic dysfunction in middle-aged and elderly populations. This ectopic ossification results in compression of the spinal cord and nerve root by the ossified ligament. Histologic studies of OPLL suggest that OPLL develops through a process of endochondral ossification (summary by Nakajima et al., 2016).
Ethylmalonic encephalopathy (EE) is a severe, early-onset, progressive disorder characterized by developmental delay / mild-to-severe intellectual disability; generalized infantile hypotonia that evolves into hypertonia, spasticity, and (in some instances) dystonia; generalized tonic-clonic seizures; and generalized microvascular damage (diffuse and spontaneous relapsing petechial purpura, hemorrhagic suffusions of mucosal surfaces, and chronic hemorrhagic diarrhea). Infants sometimes have frequent vomiting and loss of social interaction. Speech is delayed and in some instances absent. Swallowing difficulties and failure to thrive are common. Children may be unable to walk without support and may be wheelchair bound. Neurologic deterioration accelerates following intercurrent infectious illness, and the majority of children die in the first decade.
A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hyperintensity affecting a particular region of the basal ganglia.
An increased concentration of ethylmalonic acid in the urine.
Short stature, auditory canal atresia, mandibular hypoplasia, and skeletal abnormalities (SAMS) is an autosomal recessive multiple congenital anomaly syndrome with features of a first and second branchial arch syndrome. Craniofacial abnormalities can lead to conductive hearing loss, respiratory insufficiency, and feeding difficulties. Additional features include rhizomelic skeletal anomalies as well as abnormalities of the shoulder and pelvic joints. Affected individuals may also have some features of a neurocristopathy or abnormal mesoderm development, such as urogenital anomalies, that are distinct from other branchial arch syndromes (summary by Parry et al., 2013).
Bony fusion between the humerus and scapula, leading to an impairment in mobility of the affected shoulder joint.
Delayed maturation and calcification of the rami (branches) of the pubic bone.
Autosomal dominant deafness-15 is a form of progressive nonsyndromic sensorineural hearing loss with postlingual onset between the second and sixth decades of life (summary by Kim et al., 2013).
A type of severe combined immunodeficiency disease characterised by severe and recurrent infections, diarrhoea, failure to thrive, and cell sensitivity to ionising radiation. Prevalence is unknown. Results from null mutations in the DCLRE1C gene (10p13) that lead to a defect in the V(D)J recombination and thus to an early arrest of both B and T cell maturation. Transmission is autosomal recessive.
Severe combined immunodeficiency (SCID) due to DCLRE1C deficiency is a type of SCID (see this term) characterized by severe and recurrent infections, diarrhea, failure to thrive, and cell sensitivity to ionizing radiation.
Monomelic amyotrophy, also known as Hirayama disease, is characterized by insidious onset of weakness and wasting of the muscles of the hand and forearm. It is usually unilateral, but can be bilateral. It occurs most commonly as a sporadic condition, is most common in young men, and follows a relatively benign course after a few years of progression (Nalini et al., 2004; Misra et al., 2005).
Any structural anomaly of the lower motor neuron.
A dislocation of the head of the radius from its socket in the elbow joint in an proximal direction.
Absence or underdevelopment of the ulna.
Desmosterolosis is a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells (summary by Waterham et al., 2001).
Increased width of the alveolar ridges. [pmid:19125428]
Gracile bone dysplasia is a perinatally lethal condition characterized by gracile bones with thin diaphyses, premature closure of basal cranial sutures, and microphthalmia (summary by Unger et al., 2013).
Pierpont syndrome is a multiple congenital anomaly syndrome associated with learning disability. Key features include distinctive facial characteristics, especially when smiling, plantar fat pads, and other limb anomalies (summary by Burkitt Wright et al., 2011).
Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on electroretinogram. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora (summary by Suzuki et al., 2011).
Chronic loss of joint motion in the 5th finger due to structural changes in non-bony tissue. The term camptodactyly of the 5th finger is used if the distal and/or proximal interphalangeal joints are affected.
RHYNS syndrome is characterized by gaze palsy, retinitis pigmentosa, sensorineural hearing loss, hypopituitarism, nephronophthisis, and mild skeletal dysplasia (Di Rocco et al., 1997).
Idiopathic torsion dystonia (ITD) is a clinically and genetically heterogeneous group of movement disorders characterized by sustained dystonic muscle contractions causing involuntary twisting movements and/or postures, where causes such as cerebral lesions (especially of the basal ganglia), drugs, or other neurologic disorders have not been found. Adult-onset torsion dystonia usually remains focal and is localized in the upper part of the body (summary by Leube et al., 1996).
Disorder with manifestations of moderate-to-severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. The syndrome has been described in a large Missouri (US) kindred with 14 affected members in 4 generations. Though some spontaneous improvement of the skeletal defects may occur in adolescence, the affected individuals remained shorter than their age-matched unaffected siblings. Predisposition deformities to osteoarthritis have been noted. This condition is caused by mutation in the MMP13 gene (locus 11q22.3) and transmitted in an autosomal dominant manner.
Widening of the ilium ala, that is of the wing of the ilium, combined with external rotation, leading to a flared appearance of the iliac wing.
Bending of the diaphysis (shaft) of the ulna.
A type of hearing impairment caused by an abnormal functionality of the cochlear nerve with congenital onset.
Progressive cone dystrophy usually presents in childhood or early adult life, with many patients developing rod photoreceptor involvement in later life, thereby leading to considerable overlap between progressive cone dystrophy and cone-rod dystrophy. Both progressive cone dystrophy and cone-rod dystrophy have been associated with mutation in the GUCA1A gene (Michaelides et al., 2006). Intrafamilial variability in GUCA1A-associated macular disease ranges from mild photoreceptor degeneration to central areolar choroidal dystrophy (CACD), a form of retinal degeneration that primarily involves the macula and is characterized by a well-defined atrophic region of retinal pigment epithelium and choriocapillaris in the latest stage (Chen et al., 2017).
Capillary hemangiomas are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births (Mulliken and Young, 1988). Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma. Hemangiomas are classified as distinct from vascular malformations (see, e.g., CMC1, 163000; 108010; and CCM, 116860), in that the latter are present from birth, tend to grow with the individual, do not regress, and show normal rates of endothelial cell turnover (Spring and Bentz, 2005; Legiehn and Heran, 2006). Legiehn and Heran (2006) noted that the term 'hemangioma' in adults is considered inaccurate and should be discarded. Most hemangiomas occur sporadically, but some families with autosomal dominant inheritance have been reported (Walter et al., 1999).
Cysts of microscopic size confined to the cortex of the kidney.
Fibrosis of the external ocular muscles such that the eyes of affected individuals are partially or completely fixed in a strabismic position. Residual eye movements are significantly limited. [HPO:probinson]
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia of the hair/nail type is a rare congenital condition characterized by hypotrichosis and nail dystrophy without nonectodermal or other ectodermal manifestations.
Familial hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder characterized by very low serum magnesium levels. Hypocalcemia is a secondary consequence of parathyroid failure and parathyroid hormone resistance as a result of severe magnesium deficiency. The disease typically manifests during the first months of life with generalized convulsions or signs of increased neuromuscular excitability, such as muscle spasms or tetany. Untreated, the disease may be fatal or lead to severe neurologic damage. Treatment includes immediate administration of magnesium, usually intravenously, followed by life-long high-dose oral magnesium (review by Knoers, 2009). Genetic Heterogeneity of Hypomagnesemia A form of hypomagnesemia due to kidney defects and high urinary magnesium excretion associated with hypocalciuria (HOMG2; 154020) is caused by mutation in the FXYD2 gene (601814). Renal hypomagnesemia-3 (HOMG3; 248250), associated with hypercalciuria and nephrocalcinosis, is caused by mutation in the CLDN16 gene (603959). Renal hypomagnesemia-4 (HOMG4; 611718), which is normocalciuric, is caused by mutation in the EGF gene (131530). Renal hypomagnesemia-5 (HOMG5; 248190), associated with hypercalciuria, nephrocalcinosis, and severe ocular involvement, is caused by mutation in the CLDN19 gene (610036). Renal hypomagnesemia-6 (HOMG6; 613882) is caused by mutation in the CNNM2 gene (607803). Patients with Gitelman syndrome (263800) and Bartter syndrome (see 241200) also show hypomagnesemia, and steatorrhea and severe chronic diarrhea states, such as Crohn disease (see 226600) and Whipple disease, that can result in severe hypomagnesemia.
Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in the first or second decade, before the end of puberty (summary by Delatycki et al., 2000). For a general phenotypic description of Friedreich ataxia (FRDA), see FRDA1 (229300), which is caused by mutation in the FXN gene (606829) on chromosome 9q13.
Underdevelopment (hypoplasia) of the big toe.
This syndrome has characteristics of neonatal teeth, trichodystrophy and malformations of the hands and feet. To date, it has been reported in 21 patients and is transmitted as an autosomal dominant trait.
A lack of strength of the proximal muscles of the legs.
A lack of strength of the proximal muscles of the arms.
Muscular atrophy affecting proximally located muscles of the arms.
The presence of an abnormally increased amount of connective tissue.
An inherited epidermal disorder with characteristics of palmoplantar keratoderma, linear hyperkeratotic papules on the flexural side of large joints (cord-like distribution around wrists, in antecubital and popliteal folds), hyperkeratotic plaques (on neck, axillae, elbows, wrists, and knees), mild ichthyosiform scaling, and sclerotic constrictions around fingers that present flexural deformities. The disease is caused by homozygous mutation in the POMP gene.
Glomerulopathy with fibronectin deposits is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life. Pathologic examination shows enlarged glomeruli with mesangial and subendothelial fibrillary deposits that show strong immunoreactivity to fibronectin (Castelletti et al., 2008). For a discussion of genetic heterogeneity of GFND, see 137950.
Mutations in the GJA3 gene have been found to cause multiple types of cataract, which have been described as zonular pulverulent, posterior polar, nuclear coralliform, embryonal nuclear, and Coppock-like. The preferred title/symbol for this entry was formerly 'Cataract, Zonular Pulverulent 3; CZP3.'
Juvenile primary osteoporosis is a skeletal disorder characterized by thinning of the bones (osteoporosis) that begins in childhood. Osteoporosis is caused by a shortage of calcium and other minerals in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple fractures in the long bones of the arms and legs, especially in the regions where new bone forms (metaphyses). They also have fractures in the bones that form the spine (vertebrae), which can cause collapse of the affected vertebrae (compressed vertebrae). Multiple fractures can cause bone pain and lead to movement problems.
This form of autosomal recessive deafness is sensorineural and nonsyndromic, and shows prelingual onset (summary by Charizopoulou et al., 2011).
Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which the body cannot properly regulate the number of immune system cells (lymphocytes). ALPS is characterized by the production of an abnormally large number of lymphocytes (lymphoproliferation). Accumulation of excess lymphocytes results in enlargement of the lymph nodes (lymphadenopathy), the liver (hepatomegaly), and the spleen (splenomegaly).Autoimmune disorders are also common in ALPS. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Most of the autoimmune disorders associated with ALPS target and damage blood cells. For example, the immune system may attack red blood cells (autoimmune hemolytic anemia), white blood cells (autoimmune neutropenia), or platelets (autoimmune thrombocytopenia). Less commonly, autoimmune disorders that affect other organs and tissues occur in people with ALPS. These disorders can damage the kidneys (glomerulonephritis), liver (autoimmune hepatitis), eyes (uveitis), or nerves (Guillain-Barre syndrome). Skin problems, usually rashes or hives (urticaria), can also occur in ALPS.ALPS can have varying patterns of signs and symptoms. Most commonly, lymphoproliferation becomes apparent during childhood. Enlargement of the lymph nodes and spleen frequently occur in affected individuals. Autoimmune disorders typically develop several years later, most frequently as a combination of hemolytic anemia and thrombocytopenia, also called Evans syndrome. People with this classic form of ALPS generally have a near-normal lifespan, but have a greatly increased risk of developing cancer of the immune system cells (lymphoma) compared with the general population.Some people have signs and symptoms that resemble those of ALPS, including lymphoproliferation, lymphadenopathy, splenomegaly, and low blood counts, but the specific pattern of these signs and symptoms or the genetic cause may be different. Researchers disagree whether individuals with these non-classic forms should be considered to have ALPS or a separate condition.
An abnormality of the cerebellum. [HPO:probinson]
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
A very rare form of acrofacial dysostosis, reported in four members of a family from the Sicilian village of Palagonia. The syndrome has characteristics of normal intelligence, shortness of stature, and mild acrofacial dysostosis (malar hypoplasia, micrognathia and webbing of digits with shortening of the fourth metacarpals) associated with oligodontia, normal or high arched palate, aplasia cutis verticis with pili torti, mild cutaneous syndactyly of digits 2-5, webbing of digits and shortening of the fourth metacarpals and unilateral cleft lip.
Phosphoglycerate dehydrogenase deficiency is an autosomal recessive inborn error of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures (summary by Jaeken et al., 1996).
Horizontal nystagmus dating from or present at birth.
Penttinen syndrome is characterized by a prematurely aged appearance involving lipoatrophy and epidermal and dermal atrophy, as well as hypertrophic lesions that resemble scars, thin hair, proptosis, underdeveloped cheekbones, and marked acroosteolysis (Johnston et al., 2015).
Absence or failure to form of the external auditory canal. [HPO:probinson]
A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.
A congenital malformation of the pulmonary valve characterized by leaflet deformation.
A congenital malformation of the aortic valve characterized by leaflet deformation.
The presence of genetically distinct populations of somatic cells in a given organism caused by DNA mutations, epigenetic alterations of DNA, chromosomal abnormalities or the spontaneous reversion of inherited mutations.
Increased prominence or roundness of soft tissues between zygomata and mandible.
A foot for which the measured width is above the 95th centile for age; or, a foot that appears disproportionately wide for its length.
Decreased number of head hairs per unit area on the anterior region of the scalp.
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The lipopigment patterns observed most often in CLN6 comprise mixed combinations of 'granular,' 'curvilinear,' and 'fingerprint' profiles. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). Adult-onset neuronal ceroid lipofuscinosis, also known as Kufs disease, is a neurodegenerative disorder without retinal involvement. There are 2 overlapping phenotypes: type A, characterized by progressive myoclonic epilepsy, and type B, characterized by dementia and a variety of motor-system signs (summary by Arsov et al., 2011). For a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
Loss of previously present motor (i.e., movement) abilities.
The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility (Beighton et al., 1998). The major characteristics of the musculocontractural form of EDS include distinctive craniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, muscular hypotonia, hyperextensible thin skin with easy bruisability and atrophic scarring, wrinkled palms, joint hypermobility, and ocular involvement (summary by Malfait et al., 2010). Janecke et al. (2015) reviewed the clinical findings in 34 reported EDSMC patients, 31 with CHST14 mutations and 3 with DSE (605942) mutations (see 615539), and stated that the disorder can be recognized based on the presence of distal arthrogryposis, including adducted thumbs or clenched fists and talipes equinovarus, as well as hands with atypically shallow palmar creases and tapering fingers, and neonatal muscular hypotonia. Characteristic craniofacial features include brachycephaly, large fontanel, hypertelorism, downslanting palpebral fissures, microcorneae, strabismus, prominent nasolabial folds, short philtrum, thin upper lip, small mouth, high palate, microretrognathia, and prominent and often low-set and posteriorly rotated ears. In addition, EDSMC patients show muscular hypoplasia and weakness, which has been confirmed by ultrasound and electromyography, and intellectual development appears to be normal. Genetic Heterogeneity of Musculocontractural Ehlers-Danlos Syndrome Ehlers-Danlos syndrome musculocontractural type 2 (EDSMC2; 615539) is caused by mutation in the DSE gene (605942) on chromosome 6q22.
Proteus like syndrome describes patients who do not meet the diagnostic criteria for Proteus syndrome but who share a multitude of characteristic clinical features of the disease. The prevalence is unknown. The main clinical features include skeletal overgrowth, hamartomous overgrowth of multiple tissues, cerebriform connective tissue nevi, vascular malformations and linear epidermal nevi. Mutations in the PTEN gene are found in 50% of Proteus-like syndrome cases, making them a part of the PTEN harmatoma syndrome group.
Quebec platelet disorder is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. The disorder shows a favorable therapeutic response to fibrinolytic inhibitors (summary by Diamandis et al., 2009).
An exceedingly rare genetic disorder with characteristics of cutaneous pigmentation anomalies, ocular disorders and hearing loss. The syndrome was described in 1990 in two patients from the same Yemenite family. A brother and sister were described as having cutaneous patchy hypo and hyperpigmentation on the trunk and extremities, grey hair, white brows and lashes. Ocular manifestations were microcornea, coloboma and abnormalities of the anterior chamber of the eye. Both patients had severe hearing loss and dental abnormalities. Intelligence was reported to be normal. Their parents were unaffected and possibly consanguineous. The cause of this syndrome has not been determined. The inheritance pattern appears to be autosomal recessive.
T-cell immunodeficiency, congenital alopecia, and nail dystrophy is a type of severe combined immunodeficiency (SCID), which is a group of disorders characterized by an almost total lack of immune protection from foreign invaders such as bacteria and viruses. People with this form of SCID are missing functional immune cells called T cells, which normally recognize and attack foreign invaders to prevent infection. Without functional T cells, affected individuals develop repeated and persistent infections starting early in life. The infections result in slow growth and can be life-threatening; without effective treatment, most affected individuals live only into infancy or early childhood.T-cell immunodeficiency, congenital alopecia, and nail dystrophy also affects growth of the hair and nails. Congenital alopecia refers to an absence of hair that is apparent from birth. Affected individuals have no scalp hair, eyebrows, or eyelashes. Nail dystrophy is a general term that describes malformed fingernails and toenails; in this condition, the nails are often ridged, pitted, or abnormally curved.Researchers have described abnormalities of the brain and spinal cord (central nervous system) in at least two cases of this condition. However, it is not yet known whether central nervous system abnormalities are a common feature of T-cell immunodeficiency, congenital alopecia, and nail dystrophy.
Sebaceous gland hyperplasia presents as one or more elevated, soft, yellow papules with central umbilication on the face, particularly the forehead. Lesions may spread to the neck and upper part of the thorax. Sebaceous gland hyperplasia occurs frequently in older individuals, particularly in men past middle age (Nomland, 1930). A premature form has its appearance during puberty or just afterwards, male predominance, and excessive sebaceous secretion. Most cases are sporadic (summary by Boonchai and Leenutaphong, 1997).
Human personality traits that can be reliably measured by rating scales show a considerable heritable component. One such instrument is the tridimensional personality questionnaire (TPQ), which was designed by Cloninger et al. (1993) to measure 4 distinct domains of temperament--novelty seeking, harm avoidance, reward dependence, and persistence--that are hypothesized to be based on distinct neurochemical and genetic substrates. Risk-taking is a characteristic of behaviors that occur under conditions of uncertainty and involves a tradeoff between beneficial versus detrimental outcomes, perceived or real. Risk-taking may or may not involve conscious evaluation of the probability and magnitude of possible outcomes (Anokhin et al., 2009). See also harm avoidance (607834) and pathologic gambling (606349), which may be related.
Leptin (LEP; 164160) is a serum protein produced by adipocytes and is thought to play a role in the regulation of body fat. Leptin levels in humans are highly correlated with the individual's total adiposity (Maffei et al., 1995; Considine et al., 1996).
Exaggerated bulkiness of the crease or fold of skin running from the lateral margin of the nose, where nasal base meets the skin of the face, to a point just lateral to the corner of the mouth (cheilion, or commissure).
Increased number and size of the juxtaglomerular cells.
An increased concentration of prostaglandin in the urine.
Trichothiodystrophy (TTD) is a rare autosomal recessive disorder in which patients have brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern, called 'tiger tail banding,' under polarizing microscopy. TTD patients display a wide variety of clinical features, including cutaneous, neurologic, and growth abnormalities. Common additional clinical features are ichthyosis, intellectual/developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections. There are both photosensitive and nonphotosensitive forms of the disorder. TTD patients have not been reported to have a predisposition to cancer (summary by Faghri et al., 2008). Genetic Heterogeneity of Trichothiodystrophy Also see TTD2 (616390), caused by mutation in the ERCC3/XPB gene (133510); TTD3 (616395), caused by mutation in the GTF2H5 gene (608780); TTD4 (234050), caused by mutation in the MPLKIP gene (609188); TTD5 (300953), caused by mutation in the RNF113A gene (300951); and TTD6 (616943), caused by mutation in the GTF2E2 gene (189964).
The presence of discolored lateral incisors.
Neural tube defects have a birth incidence of approximately 1 in 1,000 in American Caucasians and are the second most common type of birth defect after congenital heart defects. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly (206500) (Detrait et al., 2005). Women with elevated plasma homocysteine, low folate, or low vitamin B12 (cobalamin) are at increased risk of having a child with a neural tube defect (O'Leary et al., 2005). Motulsky (1996) cited evidence from the Centers for Disease Control ( Anonymous, 1992) that folic acid given before and during the first 4 weeks of pregnancy can prevent 50% or more of neural tube defects. Botto et al. (1999) and Detrait et al. (2005) provided reviews of neural tube defects. De Marco et al. (2006) provided a detailed review of neurulation and the possible etiologies of neural tube defects.
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Some patients with ASGD3 have been reported with the following subtypes: iridogoniodysgenesis, Peters anomaly, Axenfeld anomaly, and Rieger anomaly. Iridogoniodysgenesis, which is characterized by iris hypoplasia, goniodysgenesis, and juvenile glaucoma, is the result of aberrant migration or terminal induction of the neural crest cells involved in the formation of the anterior segment of the eye (summary by Mears et al., 1996). Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (Peters, 1906). In Axenfeld anomaly, strands of iris tissue attach to the Schwalbe line; in Rieger anomaly, in addition to the attachment of iris tissue to the Schwalbe line, there is clinically evident iris stromal atrophy with hole or pseudo-hole formation and corectopia (summary by Smith and Traboulsi, 2012).
Charcot-Marie-Tooth neuropathy type 4C (CMT4C) is a demyelinating neuropathy characterized by early-onset severe spine deformities. The majority of affected children present with scoliosis or kyphoscoliosis between ages two and ten years, although earlier and later onset are observed. Slowly progressive neuropathy usually manifests in the first decade or adolescence, and occasionally earlier or later. Foot deformities (pes cavus, pes planus, or pes valgus) are common.
A type of onion bulb formation prominently affecting the area of the basal lamina.
This syndrome has characteristics of holoprosencephaly, predominantly radial limb deficiency (absent thumbs, phocomelia), heart defects, kidney malformations and absence of gallbladder. It has been described in two families (with at least seven affected persons). Variable manifestations include vertebral anomalies, cleft lip/palate, microphthalmia, absent nose, dysplastic ears, hearing loss, colobomas of the iris and retina and/or bifid uvula. Inheritance is likely to be autosomal dominant with variable expressivity.
This syndrome has characteristics of congenital conductive deafness due to stapes ankylosis, broad thumbs and first toes and hyperopia. So far, it has been described in multiple members of six families. Other skeletal malformations were also reported including short distal phalanges and syndactyly, but symphalangism is usually absent. Transmission is autosomal dominant and the syndrome is caused by mutations in the NOG gene (17q22).
A form of stapes ankylosis with congenital onset.
Presence of abnormal convexity of the upper and lower end plates of the vertebrae, i.e., an exaggerated bulging out of the upper and lower vertebral end plates.
Spondylometaphyseal dysplasia, Schmidt type has characteristics of short stature, myopia, small pelvis, progressive kyphoscoliosis, wrist deformity, severe genu valgum, short long bones, and severe metaphyseal dysplasia with moderate spinal changes and minimal changes in the hands and feet. This condition has been reported in five members of an Algerian family and one Polish boy. Autosomal dominant inheritance has been suggested, but the causative gene has not yet been identified.
The sacroiliac joint in the bony pelvis connects the sacrum and the ilium of the pelvis, which are joined by strong ligaments. The notch is located directly superior to the joint. This term refers to a reduction in the height of the notch.
Delayed maturation and calcification of the pubic bone. [HPO:probinson]
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Bulbous appearance of the anterior vertebral bodies, such that the vertebral bodies have the greatest vertical height anteriorly as well as bulbous anterior superior-inferior contours.
A lateral bending or abnormal curvature of the femur.
A rare syndrome with characteristics of split-hand and split-foot deformity and ocular abnormalities mainly a congenital nystagmus. Ten cases from four families have been reported in the literature. In some cases the hands are monodactylous. The affected patients have normal mental development. The condition seems to be autosomal dominant with a relatively high proportion of gonadal mosaicism.
Splenogonadal fusion (SGF) is a rare congenital anomaly of abnormal fusion between the spleen and the gonad or the remnants of the mesonephros. In 'continuous SGF,' there is a cord-like connection between the 2 organs, whereas in 'discontinuous SGF,' there is fusion of accessory splenic tissue and the gonad without a distinct structural connection to the spleen itself. Forty-eight percent of individuals with continuous SGF have additional malformations, compared to 9% of those with discontinuous SGF (McPherson et al., 2003).
An abnormality of ocular smooth pursuit characterized by an impairment of the ability to track horizontally moving objects.
Segmental spinal muscular atrophy is a form of anterior horn cell disease that affects predominantly the hand muscles (Kamholz et al., 1988). The disease is usually sporadic and nonprogressive.
Spinal muscular atrophy is characterized by degeneration of the anterior horn cells in the spinal cord, leading to symmetric muscle weakness and wasting. See also autosomal recessive adult-onset proximal spinal muscular atrophy (SMA4; 271150), caused by defect in the SMN1 gene (600354), and autosomal dominant childhood-onset proximal SMA (158600).
Distal hereditary motor neuronopathy (dHMN or HMN) is a heterogeneous group of neuromuscular disorders caused by anterior horn cell degeneration and characterized by progressive distal motor weakness and muscular atrophy of the peripheral nervous system without sensory impairment. Distal HMN is also referred to as spinal Charcot-Marie-Tooth disease (spinal CMT). Distal HMN is often referred to as a 'neuronopathy' instead of a 'neuropathy' based on the hypothesis that the primary pathologic process resides in the neuron cell body and not in the axons (Irobi et al., 2006). Genetic Heterogeneity of Autosomal Dominant Distal Hereditary Motor Neuronopathy Harding (1993) proposed a classification of distal HMN into 7 phenotypic subtypes according to age at onset, mode of inheritance, and presence of additional features. Those that show autosomal dominant inheritance include distal HMN type I, and II (HMN2A, 158590 and HMN2B, 608634), characterized by juvenile and adult onset, respectively; HMN type V (HMN5A, 600794 and HMN5B, 614751), characterized by upper limb involvement; HMN VII (HMN7A, 158580 and HMN7B, 607641), with vocal cord paralysis; HMN8 (600175); and HMN9 (617721). HMN2A is caused by mutation in the HSPB8 gene (608014), HMN2B by mutation in the HSPB1 gene (602195), HMN2C (613376) by mutation in the HSPB3 gene (604624), and HMN2D (615575) by mutation in the FBXO38 gene (608533). HMN5A is caused by mutation in the GARS gene (600287) and HMN5B is caused by mutation in the REEP1 gene (609139). HMN7A is caused by mutation in the SLC5A7 gene (608761). HMN7B is caused by mutation in the DCTN1 gene (601143). HMN8 is caused by mutation in the TRPV4 gene (605427). See also autosomal dominant ALS4 (602433) and congenital autosomal dominant distal SMA (600175). Genetic Heterogeneity of Autosomal Recessive Distal Hereditary Motor Neuronopathy (Distal Spinal Muscular Atrophy) Harding (1993) classified autosomal recessive distal hereditary motor neuronopathy as dHMN IV (HMN4) and dHMN III (HMN3) (see DSMA3; 607088). HMN has also been referred to as distal spinal muscular atrophy (DSMA). 'Distal' SMA is distinguished from 'proximal' autosomal recessive spinal muscular atrophy (SMA, 253300) by the primary muscles involved. DSMA here refers to the autosomal recessive forms of HMN. See DSMA1 (SMARD1; 604320), caused by mutation in the IGHMBP2 gene (600502); DSMA2 (605726), caused by mutation in the SIGMAR1 gene (601978) on chromosome 9p13; DSMA3 (607088), encompassing HMN types III and IV, which maps to chromosome 11q13; DSMA4 (611067), caused by mutation in the PLEKHG5 gene (611101); and DSMA5 (614881), caused by mutation in the DNAJB2 gene (604139). See also X-linked SMAX3 (300489).
Spheroid body myopathy is a form of myofibrillar myopathy (MFM). Myofibrillar myopathy refers to a genetically heterogeneous group of muscular disorders characterized by a pathologic morphologic pattern of myofibrillar degradation and abnormal accumulation of proteins involved with the sarcomeric Z disc (summary by Foroud et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures on one side only.
Hereditary elliptocytosis-3 is a hemolytic disorder characterized by the presence of elliptical erythrocytes and resulting in some cases in hemolytic anemia (summary by Qualtieri et al., 1997). For a general description and a discussion of genetic heterogeneity of hereditary elliptocytosis (HE), see EL1 (611804).
Spastic paraplegia 4 (SPG4; also known as SPAST-associated HSP) is characterized by insidiously progressive bilateral lower-limb gait spasticity. More than 50% of affected individuals have some weakness in the legs and impaired vibration sense at the ankles. About one third have sphincter disturbances. Onset is insidious, mostly in young adulthood, although symptoms may start as early as age one year and as late as age 76 years. Intrafamilial variation is considerable.
Diminution of tendon reflexes, which is an invariable sign of peripheral nerve disease.
A very rare inherited malformation syndrome with characteristics of omphalocele, scoliosis, mild dysmorphic features (downslanted palpebral fissures, s-shaped eyelids and thin upper lip), laryngeal and pharyngeal hypoplasia and learning disabilities.
Systemic sclerosis is a clinically heterogeneous connective tissue disorder characterized by immune activation, vascular damage, and fibrosis of the skin and major internal organs. Clinical and experimental data suggest that the disorder is multifactorial, involving both genetic and environmental factors (Fonseca et al., 2007). Gabrielli et al. (2009) provided a detailed review of scleroderma, including clinical manifestations and pathophysiology. See also Reynolds syndrome (613471), which shares some clinical features with scleroderma and CREST syndrome.
Sclerocornea is a primary anomaly in which scleralization of a peripheral part of the cornea, or the entire corneal tissue, occurs. In the peripheral type, the affected area is vascularized with regular arcades of superficial scleral vessels. In total sclerocornea, the entire cornea is opaque and vascularized (summary by Elliott et al., 1985).
This syndrome has characteristics of severe intellectual deficit, patella luxations, acromicria, hypogonadism, facial dysmorphism (including midface hypoplasia and premature frontotemporal balding). It has been described in three unrelated males.
The ulnar-mammary syndrome is an autosomal dominant disorder characterized by posterior limb deficiencies or duplications, apocrine/mammary gland hypoplasia and/or dysfunction, abnormal dentition, delayed puberty in males, and genital anomalies (Bamshad et al., 1996).
Developmental hypoplasia of the apocrine sweat glands in the region of the axilla.
Scalp-ear-nipple syndrome is characterized by aplasia cutis congenita of the scalp, breast anomalies that range from hypothelia or athelia to amastia, and minor anomalies of the external ears. Less frequent clinical characteristics include nail dystrophy, dental anomalies, cutaneous syndactyly of the digits, and renal malformations. Penetrance appears to be high, although there is substantial variable expressivity within families (Marneros et al., 2013).
A rare genetic syndrome with characteristics of cleft palate, large protruding ears, microcephaly and short stature (prenatal onset). Other skeletal abnormalities (delayed bone age, distally tapering fingers, hypoplastic distal phalanges, proximally placed thumbs, fifth finger clinodactyly), Pierre Robin sequence, cystic renal dysplasia, proximal renal tubular acidosis, hypospadia, cerebral anomalies on imaging (enlargement of lateral ventricles, mild cortical atrophy), seizures, hypotonia and developmental delay are also observed.
No identifiable superior and/or inferior lacrimal punctum.
Limited ability to straighten the arm at the elbow joint.
Visible increase in width of the hallux without an increase in the dorso-ventral dimension.
The presence of unusually deep creases (ridges/wrinkles) on the skin of sole of foot located between the first and second toe.
A type of tremors that is triggered by holding an arm in a fixed position.
Saethre-Chotzen syndrome is a genetic condition characterized by the premature fusion of certain skull bones (craniosynostosis). This early fusion prevents the skull from growing normally and affects the shape of the head and face.Most people with Saethre-Chotzen syndrome have prematurely fused skull bones along the coronal suture, the growth line that goes over the head from ear to ear. Other parts of the skull may be malformed as well. These changes can result in an abnormally shaped head, a high forehead, a low frontal hairline, droopy eyelids (ptosis), widely spaced eyes, and a broad nasal bridge. One side of the face may appear noticeably different from the other (facial asymmetry). Most people with Saethre-Chotzen syndrome also have small, unusually shaped ears.The signs and symptoms of Saethre-Chotzen syndrome vary widely, even among affected individuals in the same family. This condition can cause mild abnormalities of the hands and feet, such as fusion of the skin between the second and third fingers on each hand and a broad or duplicated first (big) toe. Delayed development and learning difficulties have been reported, although most people with this condition are of normal intelligence. Less common signs and symptoms of Saethre-Chotzen syndrome include short stature, abnormalities of the bones of the spine (the vertebra), hearing loss, and heart defects.Robinow-Sorauf syndrome is a condition with features similar to those of Saethre-Chotzen syndrome, including craniosynostosis and broad or duplicated great toes. It was once considered a separate disorder, but was found to result from mutations in the same gene and is now thought to be a mild variant of Saethre-Chotzen syndrome.
Rombo syndrome has characteristics of vermiculate atrophoderma, milia, hypotrichosis, trichoepitheliomas, and peripheral vasodilation with cyanosis and basal cell carcinomas. It has been described in four generations of one family and in two additional sporadic cases. The skin lesions become visible between 7 and 10 years of age and are most pronounced on the face. Basal cell carcinomas are frequent and develop at around 35 years of age.
Ring dermoid of cornea has characteristics of annular limbal dermoids (growths with a skin-like structure) with corneal and conjunctival extension. Less than 30 cases have been described. Transmission is autosomal dominant and mutations in the PITX2 gene on chromosome 4q25 have been suggested as a potential cause of the condition.
Deposition of calcium salts in the retina.
Retinitis pigmentosa-10 (RP10) is characterized in most patients by early onset and rapid progression of ocular symptoms, beginning with night blindness in childhood, followed by visual field constriction. Some patients experience an eventual reduction in visual acuity. Funduscopy shows typical changes of RP, including optic disc pallor, retinal vascular attenuation, and bone-spicule pattern of pigmentary deposits in the retinal midperiphery. Electroretinography demonstrates equal reduction in rod and cone responses (Jordan et al., 1993; Bowne et al., 2002; Bowne et al., 2006). For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Autosomal dominant retinitis pigmentosa (ADRP) is characterized by a typical fundus appearance, narrowed retinal vessels, and changes in the electrophysiological responses of the eye. Early signs are night blindness and constriction of the visual fields with a variable ages of onset (summary by Jay et al., 1992).
Familial retinal arterial tortuosity is characterized by marked tortuosity of second- and third-order retinal arteries with normal first-order arteries and venous system. Two-thirds of patients experience variable degrees of symptomatic transient vision loss due to retinal hemorrhage following minor stress or trauma (summary by Nischler et al., 2011).
Reticular dystrophy is a disorder of protean manifestations occurring in the retinal pigment epithelium (RPE) with little or no involvement of the neurosensory retina. The disorder may be detected at an early age and may be slowly progressive, but the prognosis for visual acuity is good. Abnormalities of dark adaptation and nyctalopia may develop with time. Electrophysiologic testing may show a normal electroretinogram (ERG), subnormal electrooculogram (EOG), and subnormal results of dark adaptation studies (summary by Kingham et al., 1978).
This syndrome has manifestation of symmetric, nonopposable triphalangeal thumbs and radial hypoplasia. It has been described in eight patients (five females and three males) spanning generations of a family. The affected males also presented with hypospadias. The syndrome is inherited as an autosomal dominant trait.
A dislocation of the head of the radius from its socket in the elbow joint in an posterior direction.
Infantile pyloric stenosis is the most common condition requiring surgical intervention in the first year of life. It typically presents in infants 2 to 6 weeks after birth. Clinically the disorder is characterized by projectile vomiting, visible gastric peristalsis, and a palpable pyloric tumor (summary by Everett et al., 2008). Mortality was high until successful treatment by pyloromyotomy was developed by Ramstedt (1912). Genetic Heterogeneity of Infantile Hypertrophic Pyloric Stenosis Multiple susceptibility loci have been implicated in IHPS including IHPS1 on chromosome 12q, IHPS2 (610260) on chromosome 16p13-p12, IHPS3 (612017) on chromosome 11q14-q22, IHPS4 (300711) on chromosome Xq23, and IHPS5 (612525) on chromosome 16q24.
An abnormal increase in magnitude of the pressure in the right atrium.
Hereditary congenital ptosis occurs in 3 main forms: simple; with external ophthalmoplegia; and with blepharophimosis. See PTOS2 (300245) for description of an X-linked form of congenital bilateral isolated ptosis.
Antecubital pterygium syndrome is an autosomal dominant disorder characterized by a fleshy web extending across the anterior aspect of the cubital fossa, absence of the long head of the triceps, limitation of full elbow extension, and missing skin creases over the terminal interphalangeal joints of the fingers (summary by Wallis et al., 1988).
Pterygium of the conjunctive refers to a wing-shaped thickening in the bulbar conjunctiva. The process begins near one corner of the eye, most commonly the inner canthus. The progressive head is typically fleshy and can infiltrate the cornea and block vision. Surgical excision is curative, although recurrence may occur after surgical removal (summary by Hecht and Shoptaugh, 1990).
This syndrome has manifestation of short stature, craniofacial anomalies and genital hypoplasia. Intellectual deficit is also found in the majority of cases, sometimes together with pterygia. Less than 20 cases have been described so far. The mode of transmission is likely to be autosomal dominant with incomplete penetrance. The syndrome is caused by unbalanced reciprocal translocations of the distal parts of chromosomes 6q and 9p, leading to partial trisomy of the distal region of chromosome 6q and partial monosomy of the distal region of chromosome 9p.
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Psoriasis (psoriasis vulgaris; PV) is a chronic inflammatory dermatosis that affects approximately 2% of the population. It is characterized by red, scaly skin patches that are usually found on the scalp, elbows, and knees, and may be associated with severe arthritis. The lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age (summary by Matthews et al., 1996). Generalized pustular psoriasis (GPP) is a life-threatening disease characterized by sudden, repeated episodes of high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis and elevated serum levels of C-reactive protein (123260) (summary by Marrakchi et al., 2011). GPP often presents in patients with existing or prior psoriasis vulgaris; however, GPP can develop without a history of PV (Sugiura et al., 2013). Palmoplantar pustulosis and acrodermatitis continua of Hallopeau represent acral forms of pustular psoriasis that have historically been grouped with GPP (summary by Setta-Kaffetzi et al., 2013). Nestle et al. (2009) provided a detailed review of the pathogenesis and genetics of psoriasis. Genetic Heterogeneity of Psoriasis and Psoriasis Susceptibility PSORS2 (602723) is caused by mutation in the CARD14 gene (607211) on chromosome 17q25, and PSORS14 (614204) is caused by mutation in the IL36RN gene (605507) on chromosome 2q14. Psoriasis susceptibility loci include PSORS1 on 6p21.3; PSORS3 (601454) on 4q; PSORS4 on 1q21; PSORS5 (604316) on 3q21; PSORS6 (605364) on 19p; PSORS7 (605606) on 1p; PSORS8 (610707) on 16q; PSORS9 (607857) on 4q31; PSORS10 (612410) on 18p11; PSORS11 (612599) on 5q31-q33; PSORS12 (612950) on 20q13; PSORS13 (614070), conferred by variation in the TRAF3IP2 gene (607043) on 6q21; and PSORS15 (616106), conferred by variation in the AP1S3 gene (615781) on 2q36. An additional putative psoriasis candidate locus has been reported on 20p (Nair et al., 1997).
Peripheral arterial stenosis with onset before the age of 50 years.
An epibulbar dermoid is a benign tumor typically found at the junction of the cornea and sclera (limbal epibullar dermoid). [HPO:probinson]
Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries before age of 45.
An extremely rare syndrome with characteristics of hypoplastic thumbs and halluces, fifth finger brachydactyly, postaxial polydactyly of the hands, short or uniphalangeal second toes with absent nails and hypospadias. It has been described in a father and his son and daughter. The affected patients have normal mental development. Except for postaxial polydactyly of the hands and uniphalangeal second toes with absent nails, features are in common with hand-foot-genital syndrome caused by mutations in the HOXA13 gene. In all three affected individuals, two different sequence alterations were identified in HOXA13 gene: a de novo missense mutation and a deletion in the promoter region of the gene, inherited from an unaffected parent, which may contribute to the phenotype in the affected individuals. The condition is inherited in an autosomal dominant manner.
An abnormality of the ability (skills) to perform a precise movement of small muscles with the intent to perform a specific act. Fine motor skills are required to mediate movements of the wrists, hands, fingers, feet, and toes.
Absence of the fifth long bone of the hand.
Osseous fusion of the lunate and triquetrum.
A developmental abnormality characterized by the absence of the fifth metatarsal bone.
De Verneuil et al. (1978) classified porphyria cutanea tarda (PCT), the most common type of porphyria, into 2 types: type I, or 'sporadic' type, associated with approximately 50% level of uroporphyrinogen decarboxylase (UROD; 613521) in liver (Elder et al., 1978; Felsher et al., 1982), and type II, or 'familial' type (176100), characterized by 50% deficient activity of the same enzyme in many tissues (Kushner et al., 1976; Elder et al., 1980). Type I is the most common form of PCT, comprising 70 to 80% of cases. The causes of the deficiency are often unclear and are probably multifactorial (review by Lambrecht et al., 2007).
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Mutations in the MVK gene have been found to cause multiple types of porokeratosis, which have been described as disseminated superficial actinic porokeratosis (DSAP), nonactinic disseminated superficial porokeratosis (DSP), porokeratosis of Mibelli, giant plaque of porokeratosis ptychotropica, hyperkeratotic porokeratosis, and linear porokeratosis. The preferred title of this entry was formerly 'Porokeratosis 3, Disseminated Superficial Actinic Type; POROK3.' Disseminated superficial actinic porokeratosis is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life (summary by Wu et al., 2004 and Zhang et al., 2012). For a discussion of genetic heterogeneity of porokeratosis, see 175800.
Familial porencephaly is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. In familial porencephaly, fluid-filled cysts develop in the brain (porencephaly) during fetal development or soon after birth. These cysts typically occur in only one side of the brain and vary in size. The cysts are thought to be the result of bleeding within the brain (hemorrhagic stroke). People with this condition also have leukoencephalopathy, which is a change in a type of brain tissue called white matter that can be seen with magnetic resonance imaging (MRI).During infancy, people with familial porencephaly typically have paralysis affecting one side of the body (infantile hemiplegia). Affected individuals may also have recurrent seizures (epilepsy), migraine headaches, speech problems, intellectual disability, and uncontrolled muscle tensing (dystonia). Some people are severely affected, and others may have no symptoms related to the brain cysts.
Presence of multiple adenomatous polyps in the colon.
Excessive growth of the craniofacial bones.
Although both preaxial polydactyly and syndactyly are cardinal features of this malformation, it is classified as a form of polydactyly because syndactyly does not occur in the absence of polydactyly (McClintic, 1935), the opposite not being true. On the other hand, polysyndactyly is here classified as a type of syndactyly because polydactyly (of the third or fourth fingers and fifth toes) does not occur in the absence of syndactyly. The thumb shows only the mildest degree of duplication, and syndactyly of various degrees affects fingers 3 and 4. The foot malformation is more constant and consists of duplication of part or all of the first or second toes and syndactyly affects all of the toes, especially the second and third.
A limb malformation syndrome, where the thumb is replaced by one or two triphalangeal digits with dermatoglyphic pattern specific of the index finger. Two forms of PPD3 have been described, unilateral and bilateral. There have been no further descriptions in the literature since 1962.
A hand-foot malformation with characteristics of triphalangeal thumbs and pre and postaxial polydactyly, isolated syndactyly or complex polysyndactyly. It has been described in some large pedigrees. Clinical presentation is variable within families, ranging from mild to severe. Malformations of the feet are usually less severe than those of the hands. Caused by duplication encompassing the limb-specific regulatory element (ZRS) of sonic hedgehog SHH, which lies in intron 5 of the limb region 1 homolog gene, LMBR1 (7q36). This syndrome is transmitted in an autosomal dominant manner with complete penetrance and variable expression.
An exceedingly rare autosomal dominant developmental anomaly reported in 1986 in nine individuals among four generations of the same family. The syndrome has clinical characteristics of four-limb postaxial polydactyly and progressive myopia. There have been no further descriptions in the literature since 1986.
In postaxial polydactyly type B the extra digit is rudimentary and poorly developed.
Autosomal dominant tubulointerstitial kidney disease, MUC1-related (ADTKD-MUC1) was previously known as medullary cystic kidney disease type 1. It is characterized by slowly progressive tubulointerstitial disease that leads to end-stage renal disease (ESRD) and the need for dialysis or kidney transplantation. ESRD typically occurs in adulthood but is extremely variable, occurring at any age between 20 and 70 years. There are no other systemic manifestations.
Aplasia (congenital absence) of the pectoralis minor.
Underdevelopment of the serratus anterior muscle, which is involved in abduction, upward Rotation, and elevation of the scapula.
Birt-Hogg-Dube syndrome (BHD; 135150), which is characterized by spontaneous pneumothorax as well as by fibrofolliculomas of the skin and increased risk of renal and colonic tumors, is caused by mutation in the FLCN gene. Gunji et al. (2007) suggested that isolated primary spontaneous pneumothorax associated with FLCN mutations may be part of the clinical spectrum of BHD, showing incomplete disease penetrance. Spontaneous pneumothorax is a complication of certain heritable disorders of connective tissue, particularly the Marfan syndrome (154700) and the Ehlers-Danlos syndrome (see, e.g., 130000). Pulmonary bullae can also occur with alpha-1-antitrypsin deficiency (613490).
Sudden onset of thrombocytopenia (reduced platelet count) within 5-10 days of the transfusion of blood products. The clinical presentation is post-transfusion purpura (PTP), wigth severe thrmbocytopenia, epistaxis, and hemorrhages.
Clumping together of platelets in the blood in a platelet aggregation test without addition of agents normally used to induce aggregation.
Pigmented paravenous chorioretinal atrophy is a stationary disease of the ocular fundus in which bone corpuscle pigmentation is seen in a paravenous distribution. Patients are usually asymptomatic; diagnosis is based on the characteristic fundus appearance. Most cases have been reported in males (summary by Traboulsi and Maumenee, 1986).
Rare syndrome with features of phocomelia (involving arms more severely), ectrodactyly, ear anomalies (bilateral anomalies of the pinnae), conductive deafness, dysmorphism (long and prominent philtrum, mild maxillary hypoplasia) and sinus arrhythmia. It has been described in four patients from two unrelated families.
An increased concentration of adrenaline in the urine.
Variation in the manner in which a trait is manifested. When there is variable expressivity, the trait may vary in clinical expression from mild to severe. For example, the condition neurofibromatosis type 1 may be mild, presenting with cafe-au-lait spots only, or may be severe, presenting with neurofibromas and brain tumors.
Pemphigus vulgaris (PV) is a rare, blistering autoimmune disease that affects the skin and mucous membranes. Patients have circulating antibody to an intercellular cement substance, and deposition in vivo of this antibody is a hallmark of the disease. The antibody appears to be pathogenetic, since newborn infants of mothers with pemphigus may have blisters, and newborn mice injected with the antibody from patients have clinical pemphigus. The disease is reported to have a particularly high incidence among Jews (summary by Ahmed et al., 1990).
A rare focal skeletal dysostosis with characteristics of symmetrical hypoplasia of the scapulae and the iliac wings of the pelvis. Approximately 10 patients have been reported so far. Additional skeletal abnormalities may include hypoplasia of the clavicles, ribs, femora and fibula, together with spina bifida and prominent lumbar lordosis. Eye anomalies (coloboma of iris and retina) have occasionally been reported. Intelligence is described as normal. Pelvis-shoulder dysplasia seems to be a genetically heterogeneous disorder but no causative genes have been identified so far.
Autosomal dominant leukodystrophy with autonomic disease (ADLD) is a slowly progressive disorder of central nervous system white matter characterized by onset of autonomic dysfunction in the fourth to fifth decade, followed in months to years by pyramidal and cerebellar involvement. Autonomic dysfunction can include bladder dysfunction, constipation, postural hypotension, feeding difficulties, erectile dysfunction, and (less often) impaired sweating. Pyramidal signs are often more prominent in the lower extremities (i.e., spastic weakness, hypertonia, clonus, brisk deep tendon reflexes, and bilateral Babinski signs). Cerebellar signs typically appear at the same time as the pyramidal signs and can include gait ataxia, dysdiadochokinesia, intention tremor, dysmetria, and nystagmus. Although cognitive function is usually preserved or only mildly impaired early in the disease course, dementia and psychiatric manifestations can occur as late manifestations. Affected individuals may survive for decades after onset.
Impotence (inability to develop or maintain an erection) resulting from abnormal functioning of the autonomic nervous system.
Char syndrome is characterized by the triad of typical facial features, patent ductus arteriosus (PDA), and aplasia or hypoplasia of the middle phalanges of the fifth fingers. Typical facial features are flat midface, flat nasal bridge and broad flat nasal tip, wide-set eyes, downslanting palpebral fissures, mild ptosis, short philtrum resulting in a triangular mouth, and thickened (patulous) everted lips.
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape. [pmid:19125427]
Fusion of the terminal/distal and middle phalanges of the 5th finger.
A rare paroxysmal movement disorder with episodes of sustained, conjugate, upward deviation of the eyes and down beating saccades in attempted downgaze (with preserved horizontal eye movements). This is accompanied by ataxic symptoms (unsteady gait, lack of balance and movement coordination disturbances) in an otherwise healthy individual. Bilateral vertical nystagmus is associated. Symptoms generally disappear spontaneously within 1-2 years after onset.
Absence or underdevelopment of the patella.
Perry syndrome is characterized by parkinsonism, hypoventilation, depression, and weight loss. The mean age at onset is 49 years; the mean disease duration is five years. Parkinsonism and psychiatric changes (depression, apathy, character changes, and withdrawal) tend to occur early; severe weight loss and hypoventilation manifest later.
Enlarged parietal foramina is an inherited condition of impaired skull development. It is characterized by enlarged openings (foramina) in the parietal bones, which are the two bones that form the top and sides of the skull. This condition is due to incomplete bone formation (ossification) within the parietal bones. The openings are symmetrical and circular in shape, ranging in size from a few millimeters to several centimeters wide. Parietal foramina are a normal feature of fetal development, but typically they close before the baby is born, usually by the fifth month of pregnancy. However, in people with this condition, the parietal foramina remain open throughout life.The enlarged parietal foramina are soft to the touch due to the lack of bone at those areas of the skull. People with enlarged parietal foramina usually do not have any related health problems; however, scalp defects, seizures, and structural brain abnormalities have been noted in a small percentage of affected people. Pressure applied to the openings can lead to severe headaches, and individuals with this condition have an increased risk of brain damage or skull fractures if any trauma is experienced in the area of the openings.There are two forms of enlarged parietal foramina, called type 1 and type 2, which differ in their genetic cause.
An autosomal dominant inherited non-dystrophic myotonia caused by mutations of the SCN4A gene. It is characterized by muscle stiffness, which is increased by exposure to cold but does not change to flaccid paralysis with intense cooling.
Difficulty releasing one's grip associated with prolonged first handgrip relaxation times.
A rare benign neoplasm that arises in the area of the nipple. Clinically, it usually presents as a tender erythematous crusting lesion with hardening of the nipple. Morphologically, there is proliferation of ducts lined with epithelial and myoepithelial cells and focal erosion of the epidermis.
The DSM-IV (American Psychiatric Association, 1994) defines panic disorder as the spontaneous, unexpected occurrence of panic attacks followed by persistent concern, worry, and anxiety about having additional panic attacks. Panic attacks are defined as a discrete period of intense fear or discomfort in which at least 4 of 13 symptom criteria are met that develop abruptly and reach a peak within 10 minutes. Some of these criteria include cardiac palpitations, sweating, feelings of choking, fear of losing control, and fear of dying. Panic disorder is divided into panic disorder with or without accompanying agoraphobia. However, agoraphobia can also occur without panic disorder, and panic attacks can occur in the absence of panic disorder. Comorbidity with depressive and addictive disorders is frequent. Barlow et al. (1994) and Smoller and Tsuang (1998) noted that because the diagnostic criteria remain purely clinical, the nosology of anxiety disorders, such as panic disorder, is controversial and evolving. Therefore, it is difficult to do genetic studies because of the difficulty in delineating overlapping phenotypes within the broader context of anxiety disorders. For example, there may be overlap of panic with specific phobias, variable expressivity of panic and anxiety or depression, or phenocopies within a family. The terms 'anxiety neurosis' and 'phobic neurosis' were used in the past (before the DSM-III in 1980) to encompass all of these disorders. Smoller and Tsuang (1998) suggested that dimensional personality traits, such as shyness, behavioral inhibition, and neuroticism (see 607834), could be used to define an anxiety phenotype. Schumacher et al. (2011) provided a review of the genetics of panic disorder. They noted that there is high (80%) comorbidity with other psychiatric disorders, including agoraphobia, mood disorders, substance abuse, and other anxiety disorders. Associated personality traits include anxiety sensitivity, behavioral inhibition, neuroticism, and harm avoidance. Women are more susceptible to development of the disorder, which has an average age of onset at 23.6 years. Genetic Heterogeneity of Susceptibility to Panic Disorder Susceptibility to panic disorder-1 (PAND1) has been mapped to chromosome 13q. See also PAND2 (607853), mapped to chromosome 9, and PAND3 (609985), mapped to chromosome 4.
Partial dorsal agenesis, or congenital short pancreas, is characterized by the presence of the accessory papilla, the terminal end of the main dorsal duct of Santorini, or the pancreatic body. All of these structures are missing in complete dorsal agenesis of the pancreas (Wildling et al., 1993).
Nasopalpebral lipoma-coloboma syndrome (NPLCS) is an autosomal dominant condition characterized by upper eyelid and nasopalpebral lipomas, colobomas of upper and lower eyelids, telecanthus, and maxillary hypoplasia (summary by Suresh et al., 2011).
Congenital nephrotic syndrome is a kidney condition that begins in infancy and typically leads to irreversible kidney failure (end-stage renal disease) by early childhood. Children with congenital nephrotic syndrome begin to have symptoms of the condition between birth and 3 months.The features of congenital nephrotic syndrome are caused by failure of the kidneys to filter waste products from the blood and remove them in urine. Signs and symptoms of this condition are excessive protein in the urine (proteinuria), increased cholesterol in the blood (hypercholesterolemia), an abnormal buildup of fluid in the abdominal cavity (ascites), and swelling (edema). Affected individuals may also have blood in the urine (hematuria), which can lead to a reduced number of red blood cells (anemia) in the body, abnormal blood clotting, or reduced amounts of certain white blood cells. Low white blood cell counts can lead to a weakened immune system and frequent infections in people with congenital nephrotic syndrome.Children with congenital nephrotic syndrome typically develop end-stage renal disease between ages 2 and 8, although with treatment, some may not have kidney failure until adolescence or early adulthood.
Parkin type of early-onset Parkinson disease is characterized by rigidity, bradykinesia, and resting tremor. Lower-limb dystonia may be a presenting sign. Onset usually occurs between ages 20 and 40 years with an average age of onset in the early to mid-thirties. The disease is slowly progressive and disease duration of more than 50 years has been reported. Clinical signs vary; hyperreflexia is common. Dyskinesia as a result of treatment with levodopa frequently occurs.
The photoparoxysmal response (PPR), also referred to as photosensitivity, is defined as the abnormal occurrence of cortical spikes or spike and wave discharges on electroencephalogram (EEG) in response to intermittent light stimulation (Doose and Waltz, 1993). Photosensitivity is a frequent finding in patients with idiopathic generalized epilepsy (see 600669), especially those with juvenile myoclonic epilepsy, suggesting a common epileptogenic pathway for both phenomena. The comorbidity of the 2 disorders suggests that presence of PPR may also increase the risk for epilepsy (Stephani et al., 2004; Tauer et al., 2005). Genetic Heterogeneity of Photoparoxysmal Response The PPR1 locus has been mapped to chromosome 6p21. See also PPR2 (609572), mapped to chromosome 13q31, and PPR3 (609573), mapped to chromosome 7q32.
Meier-Gorlin syndrome is a condition primarily characterized by short stature. It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation). After birth, affected individuals continue to grow at a slow rate. Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly). Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect.Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age).Most people with Meier-Gorlin syndrome have distinctive facial features. In addition to being abnormally small, the ears may be low-set or rotated backward. Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge.Abnormalities in sexual development may also occur in Meier-Gorlin syndrome. In some males with this condition, the testes are small or undescended (cryptorchidism). Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair.Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems.
Autoimmune Addison disease affects the function of the adrenal glands, which are small hormone-producing glands located on top of each kidney. It is classified as an autoimmune disorder because it results from a malfunctioning immune system that attacks the adrenal glands. As a result, the production of several hormones is disrupted, which affects many body systems.The signs and symptoms of autoimmune Addison disease can begin at any time, although they most commonly begin between ages 30 and 50. Common features of this condition include extreme tiredness (fatigue), nausea, decreased appetite, and weight loss. In addition, many affected individuals have low blood pressure (hypotension), which can lead to dizziness when standing up quickly; muscle cramps; and a craving for salty foods. A characteristic feature of autoimmune Addison disease is abnormally dark areas of skin (hyperpigmentation), especially in regions that experience a lot of friction, such as the armpits, elbows, knuckles, and palm creases. The lips and the inside lining of the mouth can also be unusually dark. Because of an imbalance of hormones involved in development of sexual characteristics, women with this condition may lose their underarm and pubic hair.Other signs and symptoms of autoimmune Addison disease include low levels of sugar (hypoglycemia) and sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood. Affected individuals may also have a shortage of red blood cells (anemia) and an increase in the number of white blood cells (lymphocytosis), particularly those known as eosinophils (eosinophilia).Autoimmune Addison disease can lead to a life-threatening adrenal crisis, characterized by vomiting, abdominal pain, back or leg cramps, and severe hypotension leading to shock. The adrenal crisis is often triggered by a stressor, such as surgery, trauma, or infection.Individuals with autoimmune Addison disease or their family members can have another autoimmune disorder, most commonly autoimmune thyroid disease or type 1 diabetes.
Bacterial infectious process with formation of mucopurulent membranes affecting the trachea. Causative agents include Staphylococcus, Streptococcus, Haemophilus influenzae, Pseudomonas, and Klebsiella.
A congenital cardiovascular abnormality characterized by the presence of subvalvar left ventricular outflow tract obstruction, coarctation of the aorta, and mitral stenosis.
A disorder resulting from a defect in the pattern of neuronal migration in which ectopic collections of neurons lie along the lateral ventricles of the brain or just beneath, contiguously or in isolated patches.
Underdevelopment of the vertebral artery.
An acquired pigmentation of the conjunctival epithelium associated with benign or atypical melanocytic hyperplasia. It usually affects adult Caucasians, is most often unilateral, and may progress to conjunctival melanoma.
The leakage of a substance from a fistula.
Movement of a lead away from the original implantation site. (ACC)
A partial or complete positional exchange between the penis and the scrotum, with positioning of the scrotum superior to the penis.
The presence of dilatation of the renal pelvis.
Early stage of HIV infection. Symptoms resemble INFLUENZA or INFECTIOUS MONONUCLEOSIS.
The autosomal recessive form of Weill-Marchesani syndrome is associated with Fibrillin gene mutations.
Bronchial asthma is the most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis (Laitinen et al., 2001; Illig and Wjst, 2002; Pillai et al., 2006). See 147050 for information on the asthma-associated phenotype atopy.
Familial paroxysmal nonkinesigenic dyskinesia (PNKD) is characterized by unilateral or bilateral involuntary movements. Attacks are typically precipitated by coffee, tea, or alcohol; they can also be triggered by excitement, stress, or fatigue, or can be spontaneous. Attacks involve dystonic posturing with choreic and ballistic movements, may be accompanied by a preceding aura, occur while the individual is awake, and are not associated with seizures. Attacks last minutes to hours and rarely occur more than once per day. Attack frequency, duration, severity, and combinations of symptoms vary within and among families. Age of onset is typically in childhood or early teens but can be as late as age 50 years.
In 80 to 85% of cases, congenital hypothyroidism is associated with, and presumably is a consequence of, thyroid dysgenesis (Macchia et al., 1998). In these cases, the thyroid gland can be absent (agenesis), ectopically located, and/or severely reduced in size (hypoplasia). When thyroid hormone therapy is not initiated within the first 2 months of life, congenital hypothyroidism can cause severe neurologic, mental, and motor damage (cretinism).
A form of Ehlers-Danlos syndrome (EDS) with characteristics of premature ageing with sparse hair, macrocephaly, loose elastic skin, failure to thrive, joint laxity, psychomotor retardation, hypotonia and defective wound healing with atrophic scars.
Calpainopathy is characterized by symmetric and progressive weakness of proximal limb-girdle muscles. The age at onset of muscle weakness ranges from two to 40 years. The phenotype shows intra- and interfamilial variability ranging from severe to mild. Three autosomal recessive calpainopathy phenotypes have been identified based on the distribution of muscle weakness and age at onset: Pelvifemoral limb-girdle muscular dystrophy (LGMD) (Leyden-Möbius LGMD) phenotype, the most frequently observed calpainopathy phenotype, in which muscle weakness is first evident in the pelvic girdle and later in the shoulder girdle, with onset that may occur as early as before age 12 years or as late as after age 30 years. Scapulohumeral LGMD (Erb LGMD) phenotype, usually a milder phenotype with infrequent early onset, in which muscle weakness is first evident in the shoulder girdle and later in the pelvic girdle. HyperCKemia, usually observed in children or young individuals, in which individuals are asymptomatic and have high serum creatine kinase (CK) concentrations. The autosomal dominant form of calpainopathy shows a variability of clinical phenotype, ranging from almost asymptomatic to wheelchair dependence after age 60 years in few cases with a generally milder phenotype than the recessive form. Clinical findings of calpainopathy include the tendency to walk on tiptoe, difficulty in running, scapular winging, waddling gait, and slight hyperlordosis. Other findings include symmetric weakness of proximal more than distal muscles in the limbs, trunk, and periscapular area; laxity of the abdominal muscles; Achilles tendon shortening; scoliosis; and joint contractures. Affected individuals typically do not have cardiac involvement or intellectual disability.
A semisynthetic, broad-spectrum, third-generation cephalosporin with antibacterial activity. Cefovecin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
A naturally-occurring cholestane and non-competitive, allosteric inhibitor of protein tyrosine phosphatase 1B (PTP1B), with potential hypoglycemic, anti-diabetic, anti-obesity, and antineoplastic activities. Upon administration, trodusquemine selectively targets and inhibits PTP1B, thereby preventing PTP1B-mediated signaling. This prevents the dephosphorylation of the insulin receptor, which improves insulin signaling and insulin sensitivity, and decreases blood glucose levels. In susceptible cancer cells, inhibition of PTP1B causes a reduction of tumor cell proliferation. In addition, as trodusquemine can cross the blood-brain barrier (BBB), it centrally suppresses appetite and causes weight loss. PTP1B, a tyrosine phosphatase, is elevated in certain cancer cells; it is specifically upregulated in human epidermal growth factor receptor 2 (HER2)-driven cancers where it promotes cell growth, and is correlated with a poor prognosis and increased metastatic potential. In diabetes, PTP1B upregulation plays a major role in insulin resistance.
A radiotracer consisting of methylcholine labeled with the positron-emitting radioisotope fluorine F 18 (18F-FMCH) with potential imaging use. Upon administration, 18F-fluoromethylcholine incorporates into tumor cells through an active, carrier-mediated transport mechanism for choline and then is phosphorylated intracellularly by choline kinase, an enzyme frequently upregulated in human tumors, yielding phosphoryl 18F-fluoromethylcholine. In turn, phosphoryl 18F-fluoromethylcholine is integrated into phospholipids in the cell membrane as part of phosphatidylcholine. As the proliferation of cancer cells is much higher than normal cells, tumor cells exhibit an increased rate of 18F-FMCH uptake and incorporation, allowing tumor imaging with positron emission tomography (PET).
An orally available, alpha-1 adrenoreceptor (alpha-1a) selective antagonist that can be used to relieve symptoms of benign prostate hyperplasia (BPH). Upon administration, silodosin selectively binds alpha-1a receptors located in the human prostate and bladder with high affinity and blocks signaling pathways mediated by alpha-1a. Blockade of these receptors causes smooth muscle relaxation, lowers intraurethral pressure, and results in improved urine flow and a reduction in the symptoms of BPH, such as difficulty with urinating, painful urination, urinary frequency and incomplete bladder emptying. In addition, silodosin may be used to improve lower urinary tract symptoms, which can occur after receiving radiation therapy for prostate cancer.
An indole inhibitor of cytosolic phospholipase A2alpha (cPLA2alpha, type IVA phospholipase) with antiinflammatory activity.
A small molecule with activity against human immunodeficiency virus (HIV). Raltegravir is an integrase inhibitor that blocks the integration of the viral genome into the host DNA, a critical step in the pathogenesis of HIV.
A humanized monoclonal antibody (MoAb) against human epidermal growth factor receptor (EGFR) with antineoplastic activity. Depatuxizumab targets the EGFR deletion variant, de2-7 EGFR as well as wild-type EGFR expressed in cells overexpressing the receptor, thereby preventing the activation and subsequent dimerization of the receptor; the decrease in receptor activation and dimerization result in an inhibition in signal transduction and anti-proliferative effects. This MoAb targets cells expressing aberrant EGFR, hence making it an ideal candidate for generation of radioisotope or toxin conjugates.
A Fab fragment of a recombinant, humanized monoclonal antibody directed against the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and conjugated to polyethylene glycol (PEG), with anti-inflammatory activity. Upon administration, certolizumab binds to TNF-alpha and prevents the interaction of this cytokine with endogenous cell surface receptors, thereby rendering TNF-alpha inactive and inhibiting TNF-mediated inflammatory responses. TNF-alpha is a protein involved in inflammation, cell survival, and apoptosis. Pegylation of certolizumab allows for an improved pharmacokinetic profile.
A synthetic long-acting cyclic peptide with somatostatin-like activity. Pasireotide activates a broad spectrum of somatostatin receptors, exhibiting a much higher binding affinity for somatostatin receptors 1, 3, and 5 than octreotide in vitro, as well as a comparable binding affinity for somatostatin receptor 2. This agent is more potent than somatostatin in inhibiting the release of human growth hormone (HGH), glucagon, and insulin.
An analogue of the naturally occurring tripeptide hemiasterlin, with potential antimitotic and antineoplastic activities. Taltobulin binds tubulin in a similar manner as colchicine and inhibits tubulin polymerization. This results in the disruption of the cytoskeleton, ultimately leading to cell cycle arrest in G2/M phase, blockage of cell division and apoptosis.
A semi-synthetic, orally bioavailable taxane derivative with potential antineoplastic and antiangiogenic properties. Tesetaxel binds to and stabilizes tubulin, promoting microtubule assembly and thereby preventing microtubule depolymerization. This may lead to cell cycle arrest and an inhibition of cell proliferation. This agent may also inhibit pro-angiogenic factors such as vascular endothelial growth factor (VEGF). As it represents poor substrate for P-glycoprotein-related drug resistance mechanisms, this agent may be useful for treating multi-drug resistant tumors.
A small-molecule organic arsenical with potential antineoplastic activity. Although the exact mechanism of action is unclear, darinaparsin, a highly toxic metabolic intermediate of inorganic arsenicals (iAs) that occurs in vivo, appears to generate volatile cytotoxic arsenic compounds when glutathione (GSH) concentrations are low. The arsenic compounds generated from darinaparsin disrupt mitochondrial bioenergetics, producing reactive oxygen species (ROS) and inducing ROS-mediated tumor cell apoptosis; in addition, this agent or its byproducts may initiate cell death by interrupting the G2/M phase of the cell cycle and may exhibit antiangiogenic effects. Compared to inorganic arsenic compounds such as arsenic trioxide (As2O3), darinaparsin appears to exhibit a wide therapeutic window.
A small molecule and non-prodrug analog of rapamycin with potent antitumor activity. AP23573 binds to and inhibits the mammalian target of rapamycin (mTOR), a serine/threonine kinase that is upregulated in some tumors and plays an important role downstream of the phosphatidylinositol (PI3K)/Akt (protein kinase B) signaling pathway. Inhibition of mTOR by AP23573 may lead to cell cycle arrest, and consequently blocks tumor cell growth and proliferation. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=354223&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=354223&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C49061"" NCI Thesaurus)
Reduced or lacking hair growth of the scalp.
A prodrug of the d-isomer of amphetamine, a non-catecholamine sympathomimetic amine with central nervous system (CNS) stimulating activity. Upon administration, lisdexamphetamine is converted to dextroamphetamine through cleavage of the lysine group. Dextroamphetamine acts by facilitating the release of catecholamines, particularly noradrenaline and dopamine, from its storage sites in nerve terminals in the CNS, and inhibits their uptake within the mesocorticolimbic system, a major component of the brain reward system, resulting in measurable behavioral changes such as euphoria, mental alertness and excitement and appetite suppression. As a CNS stimulant, this agent may increase blood pressure.
A natural or synthetic agent used for local application on skin, mucosa, or cavities, a Topical Anti-Infective Agent, formulated as a sterile solution or cream, commonly displays therapeutic or prophylactic antibiotic properties against infectious viral, bacterial, or protozoal agents by inhibiting growth and survival. (NCI04)
Any radiopharmaceutical agent that targets cancer cells and exerts an antineoplastic effect through radiotoxicity.
The act of separating a sub-component from the original collected specimen.
The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure. The lipopigment pattern seen most often in CLN2 consists of 'curvilinear' profiles (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
A rare genetic persistent combined dystonia with characteristics of clinical signs similar to ataxia-telangiectasia but with a later (usually adulthood) onset and slower progression. Patients typically present with extrapyramidal signs, such as resting tremor, choreoathetosis and dystonia, as the initial symptoms and later often develop mild cerebellar ataxia (with gait usually preserved). Telangiectasia and immunodeficiency may be absent but secondary features of ataxia-telangiectasia, such as risk of malignancy, dysarthria and peripheral neuropathy, are frequently present.
Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003). Genetic Heterogeneity of Restless Legs Syndrome RLS1 has been mapped to chromosome 12q. Other susceptibility loci for RLS include RLS2 (608831) on chromosome 14q13-q31; RLS3 (610438) on chromosome 9p24-p22; RLS4 (610439) on chromosome 2q33; RLS5 (611242) on chromosome 20p13; RLS6 (611185) on chromosome 6p21; RLS7 (612853) on chromosome 2p14; and RLS8 (615197) on chromosome 5q31.
Familial tumoral calcinosis (FTC) refers to a rare autosomal recessive disorder characterized by the occurrence of cutaneous and subcutaneous calcified masses, usually adjacent to large joints, such as hips, shoulders and elbows. FTC can occur in the setting of hyperphosphatemia or normophosphatemia, depending on the type of gene mutation involved.
Frontonasal dysplasia is a condition that results from abnormal development of the head and face before birth. People with frontonasal dysplasia have at least two of the following features: widely spaced eyes (ocular hypertelorism); a broad nose; a slit (cleft) in one or both sides of the nose; no nasal tip; a central cleft involving the nose, upper lip, or roof of the mouth (palate); incomplete formation of the front of the skull with skin covering the head where bone should be (anterior cranium bifidum occultum); or a widow's peak hairline.Other features of frontonasal dysplasia can include additional facial malformations, absence or malformation of the tissue that connects the left and right halves of the brain (the corpus callosum), and intellectual disability.There are at least three types of frontonasal dysplasia that are distinguished by their genetic causes and their signs and symptoms. In addition to the features previously described, each type of frontonasal dysplasia is associated with other distinctive features. Individuals with frontonasal dysplasia type 1 typically have abnormalities of the nose, a long area between the nose and upper lip (philtrum), and droopy upper eyelids (ptosis). Individuals with frontonasal dysplasia type 2 can have hair loss (alopecia) and an enlarged opening in the two bones that make up much of the top and sides of the skull (enlarged parietal foramina). Males with this form of the condition often have genital abnormalities. Features of frontonasal dysplasia type 3 include eyes that are missing (anophthalmia) or very small (microphthalmia) and low-set ears that are rotated backward. Frontonasal dysplasia type 3 is typically associated with the most severe facial abnormalities, but the severity of the condition varies widely, even among individuals with the same type.Life expectancy of affected individuals depends on the severity of the malformations and whether or not surgical intervention can improve associated health problems, such as breathing and feeding problems caused by the facial clefts.
A dual peroxisome proliferator-activated receptor (PPAR) agonist, with hypoglycemic activity. Naveglitazar binds with higher affinity to PPARgamma than to PPARalpha. Naveglitazar and its metabolites are primarily eliminated via biliary excretion.
An orally available peptidomimetic small molecule with activity against hepatitis C virus (HCV). Telaprivir is a selective protease inhibitor that targets the viral HCV NS3-4A serine protease and disrupts processing of viral proteins and formation of a viral replication complex.
The beta isoform of D-glucopyranose, a synthetic simple monosaccharide as an energy source. D-glucopyranose is oxidized in various tissues either under aerobic or anaerobic conditions through glycolysis, and the oxidation reaction produces carbon dioxide, water and ATP.
The hydrochloride salt of levonordefrin, a synthetic catecholamine and norepinephrine derivative with sympathomimetic and antihypertensive effects. Levonordefrin's antihypertensive effect is exerted through activation of alpha 2-adrenergic receptors in the cardiovascular control center of the CNS thereby suppressing the sympathetic output from the brain and subsequently lowering blood pressure. Levonordefrin binds to and activates peripheral alpha 2- adrenergic receptors, thereby causing vasoconstriction.
Nasal type extranodal NK/T-cell lymphoma that occurs in adulthood.
A nasal type extranodal NK/T-cell lymphoma occurring in childhood.
Progressive familial heart block type I (PFHBI, PFHB1) is an autosomal dominant cardiac bundle branch disorder that may progress to complete heart block (Brink and Torrington, 1977; van der Merwe et al., 1986; van der Merwe et al., 1988). It is defined on electrocardiogram by evidence of bundle branch disease, i.e., right bundle branch block, left anterior or posterior hemiblock, or complete heart block, with broad QRS complexes. Progression has been shown from a normal electrocardiogram to right bundle branch block and from the latter to complete heart block. These electrocardiographic features differentiate PFHB type I from progressive familial heart block type II (PFHBII, PFHB2; 140400), in which the onset of complete heart block is associated with narrow complexes. Electrocardiographically the changes represent, respectively, bundle branch disease (PFHB1) and atrioventricular nodal disease with an atrioventricular block and an idionodal escape rhythm (PFHB2). PFHBI is manifested symptomatically when complete heart block supervenes, either with dyspnea, syncopal episodes, or sudden death. Treatment, which is best managed by regular electrocardiographic follow-up, is by the timely implantation of a pacemaker (Brink et al., 1995). Genetic Heterogeneity of Progressive Familial Heart Block Type I Progressive familial heart block type IB (PFHB1B; 604559) is caused by mutation in the TRPM4 gene (606936) on chromosome 19q13.32.
A congenital abnormality of the cerebral hemisphere chacterized by lack of gyrations (convolutions) of the cerebral cortex. []
A Sertoli-Leydig tumor of the ovary characterized by the presence of a sarcomatoid stroma which contains primitive gonadal stromal cells. It may behave in a malignant fashion and metastasize to other anatomic sites.
An acute myeloid leukemia (AML) characterized by blasts with evidence of maturation to more mature neutrophils. (WHO, 2001)
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the intrahepatic or extrahepatic bile ducts.
A basal cell carcinoma often presenting as elevated skin nodules which may become ulcerated or cystic. In cases which present as endophytic nodules, the overlying skin surface shows indurated flat lesions. It occurs most frequently on the head. Morphologically, the neoplastic basaloid cells form lobules with peripheral nuclear palisading.
A preparation of lymphocytes harvested from a patient with an Epstein-Barr virus (EBV)-positive tumor. Ex vivo, the lymphocytes are activated against EBV-specific antigens and then returned to the patient, where they mount a specific immune response against EBV-positive tumor cells. (NCI04)
Blockage of the normal flow of the small intestinal contents in the jejunum.
An increased concentration of tyrosine in the blood.
A recombinant, soluble, hexameric fusion protein consisting of three human Fas ligand (FasL) extracellular domains fused to the dimer-forming collagen domain of human adiponectin with potential pro-apoptotic and antineoplastic activities. Assembled into a soluble hexameric structure mimicking the ligand clustering of endogenous active FasL, Fas receptor agonist APO010 activates the Fas receptor, resulting in caspase-dependent apoptosis in susceptible tumor cell populations. FasL is a transmembrane protein of the tumor necrosis factor (TNF) superfamily and a pro-apoptotic ligand for the death receptor Fas.
A synthetic kinesin spindle protein (KSP) inhibitor with potential antineoplastic activity. AZD4877 selectively inhibits microtubule motor protein KSP (also called kinesin-5 or Eg5), which is essential for the formation of bipolar spindles and the proper segregation of sister chromatids during mitosis. Inhibition of KSP results in an inhibition of mitotic spindle assembly, activation of the spindle assembly checkpoint, induction of cell cycle arrest during the mitotic phase, thereby causing cell death in tumor cells that are actively dividing. Because KSP is not involved in postmitotic processes, such as neuronal transport, AZD4877 may be less likely to cause the peripheral neuropathy often associated with the tubulin-targeting agents.
A larger than normal, microscopically elevated colonic crypt that may contain dysplastic epithelium. It is considered as a possible precursor of colonic adenoma and carcinoma.
A form of the natural substance carnitine that is being studied as a way to prevent tissue damage caused by chemotherapy. Carnitine is made in muscle and liver tissue and is found in certain foods, such as meat, poultry, fish, and some dairy products. It is used by many cells in the body to make energy from fat.
The hydrochloride salt form of acolbifene, a fourth-generation estrogen receptor modulator (SERM) with potential lipid lowering and antineoplastic activity. Acolbifene specifically binds to estrogen receptors in responsive tissue, including liver, bone, breast, and endometrium. The resulting ligand-receptor complex is translocated to the nucleus where, depending on the tissue type, it promotes or suppresses the transcription of estrogen-regulated genes, thereby exerting its agonistic or antagonistic effects. Acolbifene acts as an estrogen antagonist in uterine and breast tissue, thereby blocking the effects of estrogen in these tissues. This may inhibit tumor cell proliferation in ER-positive tumor cells. This agent functions as an estrogen agonist in lipid metabolism, thereby decreasing total and LDL cholesterol levels. In bone, it decreases bone resorption and bone turnover and increases bone mineral density.
A lung adenocarcinoma consisting of a bronchioloalveolar component and an invasive adenocarcinomatous component.
A granulosa cell tumor occurring in the ovary and rarely in the testis. It is composed of granulosa cells in an often fibrothecomatous stroma. The neoplastic cells may form various patterns including the microfollicular, which is characterized by the presence of Call-Exner bodies, macrofollicular, insular, trabecular, and diffuse pattern. In females, it affects middle aged to post-menopausal women. Signs and symptoms include abdominal mass, hemoperitoneum, and ascites. Estrogenic and rarely androgenic manifestations may be present. The vast majority of cases present as stage I tumors; however, all tumors have a potential for aggressive clinical course. In males, it is reported in the age range of 16-76 years and the average age at presentation is 44 years. A minority of patients have gynecomastia. Metastases have been reported in a minority of patients.
A benign or malignant lesion arising during adulthood.
A part of the body showing particular characteristics.
The device fails to emit an audible alarm.
A device does not display an alarm message when required.
The monohydrate form of the alpha isoform of D-glucopyranose, a synthetic simple monosaccharide that is used as an energy source. D- glucopyranose is oxidized in various tissues under either aerobic or anaerobic conditions through glycolysis; the oxidation reaction produces carbon dioxide, water, and ATP.
Problem associated with any undesired acoustic energy or vibration that tends to interfere with the operation of the device.
Problem associated with compromised device performance at the ambient temperature or the storage at an inappropriate ambient temperature.
A non-neoplastic, congenital or non-congenital disorder charcaterized by marked reduction or absence of megakaryocytes and thrombocytopenia.
A C-C Chemokine Receptor Type 5 (CCR5) antagonist with activity against the human immunodeficiency virus, HIV-1. Ancriviroc is an orally bioavailable small molecule inhibitor of HIV-1 entry via CCR5 coreceptor interaction.
An herbal extract derived from the root of the plant Angelica sinensis with possible antiinflammatory, antispasmodic, vasodilatory, estrogenic, and antitumor activities. Angelica sinensis contains volatile oils, including safrole, isosafrole, and n-butylphthalide; coumarin derivatives, including psoralens, bergapten, osthol, imperatorin, and oxypeucedanin; and ferulic acid. The coumarin derivatives in this agent may vasodilate and relax smooth muscle and may exhibit additive anticoagulant effects. Ferulic acid, a phenolic phytochemical present in plant cell walls, may neutralize free radicals such as reactive oxygen species. In addition, Angelica sinensis extract has been shown to inhibit the growth and induce apoptosis of glioblastoma mutltiforme brain tumor cells through p53-dependent and p53-independent pathways.
Angina pectoris which leads an individual to seek medical attention.
A neoplasm with neuroendocrine differentiation that arises from the appendix. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
Problem associated with the requirement for software to fulfill its function within an intended use or application.
Problem associated with installing updates to a software system that affects a device performance or communication with another device.
Problem associated with electrical current flowing through a gap between two conductive surfaces, typically resulting in a visible flash of light.
Problem associated with electrical current flowing through a gap between electrodes (conductive surfaces), typically resulting in a visible flash of light.
Problem associated with electrical current flowing through a gap between paddles (conductive surfaces), typically resulting in a visible flash of light.
A sesquiterpene lactone peroxide and dimerized plant product derived from Artemisia annua L with anti-malarial, anti-proliferative and anti-angiogenic effects. Artemisinin contains an endoperoxide moiety which forms free radicals when it reacts with iron. The resultant carbon-based radical can lead to cellular damage and cell death by reacting with cellular macromolecules such as proteins and membrane lipids. Malaria parasites contain large amounts of heme-iron, a product from the digestion of hemoglobin. However, recently it has been suggested that activation of artemisinin inside the parasite is by ferrous iron. Furthermore, due to their rapid rate of division, cancer cells require and uptake a large amount of iron to proliferate, therefore they are more susceptible to the cytotoxic effect of artemisinin than non-cancerous cells. The dimer configuration has been shown to increase compound stability and reduce general toxicity.
Problem associated with impurities or interference in a signal (e.g. ECG artifact).
Problem associated with a pacing transmission process such that between any two significant instants in the same group, there is always an integral number of unit intervals. Between two significant instants located in different groups, there are not always an integral number of unit intervals.
An invasive ductal breast carcinoma characterized by the presence of a predominantly syncytial architectural pattern. It may have some, but not all the strictly defined additional morphologic criteria which are necessary for the diagnosis of medullary breast carcinoma (presence of a diffuse lymphoplasmacytic infiltrate, neoplastic round cells with abundant cytoplasm and vesicular nuclei, complete histological circumscription, and absence of glandular or tubular structures). It does not have the relatively favorable outcome that characterizes medullary breast carcinoma.
Any substance that inhibits Aurora kinase, a serine/threonine kinase that is involved in mitotic spindle morphology, centrosome function, chromatid separation, and cytokinesis. Aurora kinases are overexpressed in a variety of human cancers.
A topical preparation of baclofen, amitriptyline, and ketamine compounded in a penetration-enhancing polaxamer-lecithin organogel (PLO) with potential antineuralgic activity. The gamma-aminobutyric acid (GABA) analogue baclofen appears to activate the inhibitory GABA(B) receptor, a G protein-coupled receptor, which may result in hyperpolarization of the neuronal cell membrane and inhibition of neurotransmitter release. Amitriptyline likely produces antineuralgic effects via modulation of multiple subtypes of glutamate (Glu) receptors, independent of its antidepressant actions. Ketamine displays complex pharmacologic actions including biogenic amine uptake inhibition, interaction with opioid receptors, and inhibition of N-methyl D-aspartate (NMDA) receptors. Stimulation of GABA(B) receptor activity, modulation of Glu receptor activity, and inhibition of NMDA receptor activity may be of benefit in managing neuropathic pain.
Problem associated with undesired microbial contamination of the device.
The hydrochloride salt of the semi-synthetic camptothecin analogue belotecan with potential antitumor activity. Belotecan binds to and inhibits the activity of topoisomerase I, stabilizing the cleavable complex of topoisomerase I-DNA, which inhibits the religation of single-stranded DNA breaks generated by topoisomerase I; lethal double-stranded DNA breaks occur when the topoisomerase I-DNA complex is encountered by the DNA replication machinery, DNA replication is disrupted, and the tumor cell undergoes apoptosis. Topoisomerase I is an enzyme that mediates reversible single-strand breaks in DNA during DNA replication.
A rare, unilateral, benign embryonic neoplasm typically presenting as a cilliary body mass during childhood. It is composed of medullary epithelial cells.
A rare, unilateral, benign embryonic neoplasm typically presenting as a cilliary body mass during childhood. It is composed of medullary epithelial cells and heterologus elements, particularly cartilage, skeletal muscle, and brain tissue.
A Sertoli cell tumor of the testis or the ovary which remains localized and does not metastasize to another anatomic site.
A teratoma with benign morphologic features without metastatic potential.
The monohydrate form of the beta isoform of D-glucopyranose, a synthetic simple monosaccharide as an energy source. D-glucopyranose is oxidized in various tissues either under aerobic or anaerobic conditions through glycolysis, and the oxidation reaction produces carbon dioxide, water and ATP.
Problem associated with undesirable local or systemic effects due to exposure to device materials or leachates from those materials by a patient who has an implant or is receiving treatment with a device made from them.
Problem associated with the undesired introduction of a biofilm coating into or onto the device.
A clinical finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v6 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, and biopsy.
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
Bladder cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Bladder cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Bladder cancer in which there is no regional lymph node metastasis. (from AJCC 6th and 7th Eds.)
Bladder cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Bladder cancer in which there is no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Bladder cancer with tumor invading subepithelial connective tissue. (from AJCC 6th and 7th Eds.)
Bladder cancer with tumor invading the perivesical tissue. (from AJCC 6th and 7th Eds.)
Bladder cancer with microscopic invasion into the perivesical tissue. (from AJCC 6th and 7th Eds.)
Bladder cancer with tumor macroscopically invading the perivesical tissue (extravesical mass). (from AJCC 6th and 7th Eds.)
Bladder cancer with tumor invading pelvic wall, abdominal wall. (from AJCC 6th and 7th Eds.)
Bladder cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Bladder cancer with a finding of noninvasive papillary carcinoma. (from AJCC 6th and 7th Eds.)
Bladder cancer with a finding of carcinoma in situ: 'flat tumor'. (from AJCC 6th and 7th Eds.)
Continuous flow of fluid (e.g. liquid, gas) against the intended flow direction.
Problem related to an obstruction or blockage within the device component (e.g. tube, opening, pipe) that results in a reduction of the flow rate.
Problem associated with linking of a device whereby their functional units set up to provide means for a transfer of fluid, gas, or data is prevented or impeded.
A benign melanocytic nevus that arises from the breast skin.
A benign, well circumscribed neoplasm that arises from the breast. It is composed entirely of tubular structures that contain epithelial and myoepithelial cells.
Problem associated with an undesired bulge, bend, bow, kink, or wavy condition observed in the device material resulting from compressive stresses.
Problems associated with a discoloration or destruction as a result of thermal decomposition of the device.
A synthetic cyclic heptapeptide with potential antineoplastic activity. Pyruvate kinase (PK) inhibitor TLN-232 targets pyruvate kinase M2 (M2PK), which may disrupt tumor cell anaerobic glycolysis. M2PK is a dimeric isoform of PK and the predominant PK isoform found in tumor cells
A humanized immunotoxin directed against the Lewis Y antigen conjugated with calicheamicin, a hydrophobic enediyne antibiotic, with potential antineoplastic activity. CMD193 binds to the Lewis Y antigen, a tetrasaccharide expressed on the cell surfaces of many tumor cell types. Upon binding, CMD-193 is internalized, thereby delivering the attached calicheamicin to Lewis Y antigen-expressing tumor cells. Calicheamicin binds non-covalently to the minor groove of DNA and prompts conformational changes and DNA oxidation, thereby inhibiting DNA synthesis and inducing apoptosis.
Problem associated with buildup of calcium salts on a device.
Problem associated with the transfer of energy within an electrical network by means of the capacitance between circuit nodes. It occurs when energy is coupled from one circuit to another through an electric field.
Problem associated with the inability of the device to achieve successful depolarization and contraction of a cardiac chamber caused by a pacemaker output pulse.
A malignant tumor arising in the epithelial cells of the brain or spinal cord.
Problem associated with the premature ending of the charging process (e.g. of a battery or other charge storage device).
Problem associated with an unexpected amount of time required to charge the device (e.g. a delay in starting charging or a longer than expected charge time).
Any agent that binds to and blocks any of the chemokine receptor subtypes. Chemokine receptors, members of the G-protein coupled receptor family, are predominantly expressed on the surface of leukocytes and play an important role in inflammation, infectious diseases, and cancer.
A benign or malignant lesion arising during childhood.
Any substance that capable of promoting bile flow into the intestine, especially as a result of contraction of the gallbladder, or of stimulating the liver to increase output of bile.
An immunophenotypic test result indicating positive staining of neoplastic cells for chromogranin A.
A psychotropic agent similar to doxepin with potential antianxiety and antidepressant activities. Although its exact mechanism of action has yet to be fully elucidated, cidoxepin may act similarly to doxepin. Cidoxepin may inhibit the reuptake of serotonin and noradrenaline from the synaptic cleft, thereby increasing their activity. This may account for its antianxiety and antidepressant effects.
The hydrochloride salt form of cidoxepin, a psychotropic agent similar to doxepin with potential antianxiety and antidepressant activities. Although its exact mechanism of action has yet to be fully elucidated, cidoxepin may act similarly to doxepin. Cidoxepin may inhibit the reuptake of serotonin and noradrenaline from the synaptic cleft, thereby increasing their activity. This may account for its antianxiety and antidepressant effects.
Problem associated with a failure of the internal network paths or electrical circuitry (i.e. electrical components, circuit boards, wiring).
Problem associated with the presence of any unexpected foreign substance found in a device, on its surface or in the package materials, which may affect performance or intended use of the device, or problem that compromise effective decontamination of the device.
A malignant neoplasm characterized by the presence of atypical cells with clear cytoplasm.
A benign cystic glandular epithelial neoplasm characterized by the presence of neoplastic clear or hobnail cells which form papillary structures. There is no evidence of stromal invasion.
Problem associated with the aggregation of particles into irregular masses.
Problem associated with the undesired characterization of congealing, solidifying, thickening, curdling.
A homeopathic herbal formulation with potential anti-emetic activity. Cocculus/nux vomica/tabacum/petroleum extract contains equal homeopathic units of the following extracts: extract of Cocculus indicus (fish berry), the fruit of the southeast Asian/Indian climbing plant Anamirta cocculus; extract of the seeds of Strychnos nux vomica (poison nut), an evergreen tree native to southeast Asia; extract of Nicotiana tabacum (tobacco); and petroleum. Although the exact mechanism(s) of action for this formulation has yet to be fully elucidated, alkaloids in these plant extracts have been shown to relieve nausea, vomiting, and, in some cases, dizziness.
A rare, invasive colon adenocarcinoma characterized by the presence of sheets of malignant epithelial cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. It usually has a favorable prognosis.
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
Colorectal cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Colorectal cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Colorectal cancer in which distant metastases cannot be assessed. (from AJCC 6th Ed.)
Colorectal cancer without regional lymph node metastasis. (from AJCC 6th and 7th Eds.)
Colorectal cancer with metastasis in 1-3 regional lymph nodes. (from AJCC 6th Ed.)
Colorectal cancer with metastasis in four or more regional lymph nodes. (from AJCC 6th Ed.)
Colorectal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Colorectal cancer with no evidence of primary tumor. (from AJCC 6th and 7th Eds.)
Colorectal cancer with invasion into the submucosa. (from AJCC 6th and 7th Eds.)
Colorectal cancer with invasion into the muscularis propria. (from AJCC 6th and 7th Eds.)
Colorectal cancer with invasion through the muscularis propria into the submucosa, or into non-peritonealized pericolic or perirectal soft tissues. (from AJCC 6th Ed.)
Colorectal cancer with invasion through the muscularis propria into the submucosa, or into non-peritonealized pericolic or perirectal soft tissues, with tumor extension of 5 mm or less beyond the border of the muscularis propria. (from CAP Colorectal Cancer Protocol-January 2005 Revision)
Colorectal cancer with invasion through the muscularis propria into the submucosa, or into non-peritonealized pericolic or perirectal soft tissues, with tumor extension of more than 5 mm beyond the border of the muscularis propria. (from CAP Colorectal Cancer Protocol-January 2005 Revision)
Colorectal cancer with direct invasion of adjacent organs or structures and/or perforation of the visceral peritoneum. Direct invasion in T4 includes invasion of other segments of the colorectum by way of the serosa. Invasion of the sigmoid colon by a carcinoma of the cecum, for example, should be classified as T4. Tumor that is adherent to other organs or structures macroscopically is classified as T4. However, if on microscopic examination, no tumor is present in the adhesion, the classification should be pT3. V and L substaging should be used to indicate the presence or absence of vascular or lymphatic invasion. (from AJCC 6th Ed.)
Colorectal cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Colorectal cancer in situ in which cancer cells are confined within the glandular basement membrane (intraepithelial). (from CAP Colorectal Cancer Protocol-January 2005 Revision)
Colorectal cancer in situ involving the lamina propria (intramucosal) without extension through the muscularis mucosa into the submucosa. (from CAP Colorectal Cancer Protocol-January 2005 Revision)
Colorectal cancer in situ with cancer cells confined within the glandular basement membrane (intraepithelial) or within the lamina propria (intramucosal) without extension through the muscularis mucosa into the submucosa. (from AJCC 6th Ed.)
Problem associated with a device sending or receiving signals or data. This includes transmission among internal components of the device to which the device is intended to communicate.
Problem associated with software, firmware, and/or hardware elements that control the execution of computer programs and provides such services as computer resource allocation, job control, input/output control, and file management in a computer system.
Issue associated with written programs, codes, and/or software system that affects device performance or communication with another device.
Problem associated with unauthorized access to or modification of a software system resulting in a loss of confidentiality, integrity, or availability of written program code, application software, or data or entire device.
Problem associated with users being unclear and not able to follow any written, printed, or graphic matter that is affixed to device or its packaging with any matter that accompanies a medical device including verbal instructions related to identification, technical description and use of the device provided by a medical device manufacturer that vary from the standard of medical care in a given environment.
Inherited disorders involving abnormalities of red blood cell function, structure, or production. Some diseases in this group may be associated with bone marrow failure, neutropenia, and/or thrombocytopenia.
A group of rare inherited platelet disorders that involve abnormalities of platelet function or platelet production and that usually cause moderate to severe bleeding problems.
Problem associated with the undesired introduction of impurities either chemical or microbiological in nature, or of foreign matter into or onto the device ingredient or reagent.
Problem associated with the excessive production of electrical impulses over a period.
Problem associated with the use of the device in terms of inappropriate and false control setting for the device's specified operation and/or intended use.
The act of producing a chemical structure with a high molecular weight that is comprised of two or more monomer subunits. The two monomers can be of the same or different composition and polymerize simultaneously. Several different classes and types of copolymers exist.
Problem associated with the chemical or electrochemical reaction between materials, usually a metal and its environment that produces a deterioration of the metal and its properties.
A distinctive Crohn's disease-like reaction (CLR) consisting of discrete lymphoid aggregates, some with germinal centers, and surrounding stellate fibrosis commonly found around colorectal adenocarcinomas in the absence of clinical or pathologic evidence of prior Crohn's disease.
Problem associated with the degree to which an antibody or antigen participates in cross reactions.
Indicates a person who has smoked at least 100 cigarettes in his or her lifetime, who smokes now, but does not smoke every day.
The anhydrous form of cyclophosphamide, a synthetic nitrogen mustard alkylating agent, with antineoplastic and immunosuppressive activities. In the liver, cyclophosphamide is converted to active metabolites including phosphoramide mustard, which binds to and crosslinks DNA and RNA, thereby inhibiting DNA replication and protein synthesis. This agent, at low doses, is also a potent immunosuppressant primarily by depleting T-regulatory cells.
A regimen consisting of dexamethasone, etoposide, cytarabine and L-asparaginase, used for the treatment of recurrent childhood Non-Hodgkin lymphoma.
A racemic mixture of 5-hydroxytryptophan (5-HTP), a precursor to the neurotransmitter serotonin with anti-depressant, analgesic and appetite-suppressant activities. DL-5-HTP is decarboxylated to serotonin by aromatic-L-amino-acid decarboxylase, and results in increased serotonin levels within the brain. Mediated through serotonin receptors, elevated levels of serotonin causes increased serotonin neurotransmissions, hence leading to release of depression, pain and appetite.
A racemic mixture of limonene, a natural cyclic monoterpene and major component of the oil extracted from citrus rind with chemo-preventive and antitumor activities. The metabolites of DL-limonene, perillic acid, dihydroperillic acid, uroterpenol and limonene 1,2-diol are suggested to inhibit tumor growth through inhibition of p21-dependent signaling, induce apoptosis via the induction of the transforming growth factor beta-signaling pathway, inhibit post-translational modification of signal transduction proteins, result in G1 cell cycle arrest as well as cause differential expression of cell cycle- and apoptosis-related genes.
A racemic mixture of liothyronine, a synthetic version of triiodothyronine (T3), the primary active thyroid hormone. Like endogenous T3, DL-liothyronine exerts its many metabolic effects through control of gene expression, thereby resulting in the production of proteins that are involved in normal metabolism, growth, and development. Other physiologic effects of liothyronine include promoting gluconeogenesis, increasing utilization and mobilization of glycogen stores, and elevating basal metabolic rate.
A racemic mixture of proline, an imino acid. Proline is found in cartilage and is important for maintaining youthful skin as well as repair of muscle, connective tissue and skin damage. It is also essential for the immune system and an essential component of collagen and is important for proper functioning of joints and tendons. Proline is important for the proper functioning of joints and tendons and helps maintain and strengthen heart muscles.
A racemic mixture of propoxyphene, a synthetic opiate agonist with narcotic analgesic activity. The analgesic effect of propoxyphene is due to its d-isomer, dextropropoxyphene, which bind to opiate receptors, primarily the OP3 receptor located within the central nervous system (CNS). Mediated through G-protein coupled OP3 receptors and cAMP signaling, the release of nociceptive neurotransmitters such as substance P, gamma-aminobutyric acid (GABA), dopamine, acetylcholine, and noradrenaline is inhibited. Propoxyphene also inhibits the release of vasopressin, somatostatin, insulin and glucagon and close N-type voltage-operated calcium channels and open calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization and reduced neuronal excitability.
Problem associated with an access that was not permitted to the computer system that may lead to modification of program, corruption of data, or and break in network security. This concept is closely associated with computer integrity which is the degree to which a system or component prevents unauthorized access to, or modification of, computer programs or data.
Problems relating to a system, component, file, procedure, or person available to replace or help restore a primary item in the event of a failure or externally caused disaster.
Event in which data is unintentionally permanently or temporarily lost, deleted, corrupted, or overwritten.
Problem associated with the device being unassociated in such a way that fluid, gas, power or signal information may not be transferred from one device to another.
Unintended decrease in pressure, compromising a medical device's intended function.
Problem associated with the removal of fluid or gas from a body cavity due to decreased suction.
Unintended decrease in pump speed and subsequent flow rate, compromising the intended function of a medical device.
Expansion of a malignant cellular infiltrate far downward into the soft tissues.
The device alarm does not operate as expected and/or in agreement with device's specifications.
Problem associated with having flaws or dimensional deviations greater than acceptable for the intended use of the device.
Problem associated with the inability of the device to release its contents.
Problem associated with an undesired material change in shape or property caused by external forces.
A combination preparation of 1:1 mixture of two immunotoxins, HD37-dgA and RFB4-dgA, with potential antineoplastic activity. Both anti-CD19 IgG monoclonal antibody HD37 and anti-CD22 IgG monoclonal antibody RFB4 are attached to a single deglycosylated ricin A chain (dgA) via N-succinimidyl-oxycarbonyl-alpha-methyl-alpha-(2-pyridyldithio) toluene (SMPT) linker. CD19 and CD22 molecules are cell suface antigens present on the majority of B acute lymphoblastic leukemia cells. This combination agent is able to specifically recognize and bind to CD19 and CD22 expressing tumor cells, thereby targeting the delivery of the cytotoxic ricin A chain to leukemia cells expressing these antigens. Ricin A chain is toxic to ribosomal activity and protein synthesis, and inhibits cell growth.
A device alarm system operates with delay.
A morphologic finding indicating the presence of a dense, collagenous stroma associated with a cellular infiltrate in a tissue sample.
Problem associated with a undesired change in shape, characterized by the presence of a slight hollow (dent) in the device surface.
Problem associated with users experiencing difficulty or delay to position the device to a specified location.
A synthetic phenethylamine bicyclic derivative with antidepressant activity. Desvenlafaxine is a selective reuptake inhibitor of serotonin and norepinephrine due to its high binding affinities to the pre-synaptic serotonin and norepinephrine transporters. By blocking both transporters, this agent prolongs neurotransmitter activities of both serotonin and norepinephrine, thereby alleviating depressive state.
Problem associated with the separation of the device from its physical construct, integrity, or chassis.
Problem associated with the failure of the device which is unable to regain a standard level of accuracy when performing a calibration procedure or process designed to assure the accuracy and proper performance of the device.
Problem associated with the device feature that are designed to respond to a physical stimulus (temperature, illumination, motion, cardiac rhythms) and that do not transmit a resulting signal for interpretation or measurement.
Problem associated with difficulty moving the device to an intended location (e.g. difficulty in advancing guide wire).
Problem associated with the use of the device in terms of the user experiencing difficulty to close or to spread out/extend length of the device, even if the operation is being performed according to labeled instructions for use.
Problem associated with problems introducing or inserting the device, even if the user is operating the device in accordance with the instructions for use or labeling.
Problem associated with difficulty of a transponder system to trigger a response.
Problem associated with difficulty for users to operate the device, specifically as it relates to the opening or removal of the outer wrapping.
The device that is difficult to program, calibrate or set to desired state, even by appropriately trained user/operator.
Problem associated with the use of the device in terms of user experiencing difficulty to take out or get rid of the device, even if the user is operating device in accordance with the instructions for use or labeling.
A childhood condition in which abnormal tissue grows on the outer part of one or both kidneys. Diffuse hyperplastic perilobar nephroblastomatosis usually develops into Wilms tumor (a type of childhood kidney cancer) if not treated.
A beta-2 -adrenergic agonist with bronchodilator activity. Dioxifedrine selectively binds to and activates beta-2 adrenergic receptors in bronchiolar smooth muscle, thereby causing stimulation of adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased intracellular cAMP levels cause relaxation of bronchial smooth muscle. This increases air flow and prevents bronchospasms and may eventually lead to an improvement of airway function.
Problem associated with an undesired streak, pattern and/or a noticeable change in color from the rest of the materials used in the device construction.
Problem associated with the linking of the device having a sufficient open space to prevent gas, liquid or electrical current flow between connectors.
Problem associated with material breaking into small pieces.
Problem associated with legibility of the device display, compromising for instance, the reading/interpretation of patient parameters or test results. Legibility problems can be due to color, size of font, display screen contrast or other factors.
A benzenedisulfonamide and carbonic anhydrase (CA) inhibitor with diuretic activity. Disulfamide inhibits CA, thereby preventing sodium, bicarbonate and thus water reabsorption in the proximal convoluted tubule resulting in diuresis.
A 4-ethylthio-3-methylpyridine analogue of omeprazole with no substituent on the benzimidazole ring, with selective and irreversible proton pump inhibitor activity. Once converted to its active sulfenamide form, disuprazole forms a stable disulfide bond with the sulfhydryl group of the hydrogen-potassium (H+/K+) ATPase found on the secretory surface of parietal cells, thereby inhibiting the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen and suppressing gastric acid secretion.
A nitrosourea compound with alkylating activity. Ditiomustine crosslinks DNA, resulting in the inhibition of DNA replication and eventually cellular proliferation.
The answer is not known by the person answering.
Problem associated with the written program code or application software used by a device to calculate specific measurements or quantities managed by the device.
A ductal carcinoma in situ of the breast in which the tumor cells fill the ductal spaces as solid sheets.
Problem associated with a device not being as sharp as intended or expected.
A folate receptor-targeting cytotoxic agent with potential antineoplastic activity. Folate receptor-targeted vinca alkaloid/mitomycin C EC0225 contains two potent cytotoxic agents, a vinca alkaloid and mitomycin C, linked to a single folate molecule. Mediated through the folate moiety, this agent delivers the cytotoxic agents directly into cells expressing folic acid receptors, frequently upregulated in many types of tumor cells. After ligand-receptor internalization, the vinca alkaloid moiety binds to tubulin and disrupts microtubule assembly-disassembly dynamics, resulting in cell cycle arrest and apoptosis. Mitomycin C alkylates DNA, producing DNA cross-links and inhibiting DNA replication. The relative tumor cell specificity of EC0225 reduces the toxicity profiles of its cytotoxic agent moieties.
An electrocardiographic finding of initial slurring (delta wave) of the QRS complex due to the presence of an accessory pathway. This characteristic ECG pattern is typically seen in Wolff-Parkinson-White syndrome. (CDISC)
The maximum elevation of the ST segment, obtained from a set of measurements of the elevation of the ST segment.
The average elevation of the ST segment, obtained from a set of measurements of the elevation of the ST segment.
The minimum elevation of the ST segment, obtained from a set of measurements of the elevation of the ST segment.
A small molecule tubulin polymerization inhibitor with potential antineoplastic activity. Microtubulin inhibitor EPC2407 binds to the colchicine-binding site on beta-tubulin and inhibits the polymerization of tubulin into microtubules, which may result in cell cycle arrest, the induction of apoptosis, and the inhibition of tumor cell proliferation. As a vascular disruption agent (VDA), this agent also disrupts tumor neovascularization, which may result in a reduction in tumor blood flow and tumor hypoxia and ischemic necrosis.
An electrocardiographic finding of a regular atrial rhythm with atrial rate of less than 101 beats per minute which does not originate in the sinus node, and which is characterized by P waves whose morphology differs from the P wave morphology during sinus rhythm. (CDISC)
Problem associated with electrical activity of the device that exceeded the specified threshold limit of the internal integrated circuitry.
Problem associated with the quality of the facility-supplied power to the device.
Problem associated with an electric current travelling along an accidental path (unintended path) in a circuit.
Problem associated with the discharge of electricity between two bodies previously electrically charged.
Problem associated with the ability of a system to function in its electromagnetic environment without introducing intolerable disturbances to anything in its environment.
Problem associated with a measure of electromagnetic radiation from equipment.
The orally active ethanolamine salt of eltrombopag, a small-molecule, nonpeptide thrombopoietin receptor agonist with megakaryopoiesis-stimulating activity. Eltrombopag binds to and stimulates the transmembrane domain of the platelet thrombopoietin receptor (TPO-R or CD110), a member of the hematopoietin receptor superfamily. Activation of TPO-R leads to the proliferation and differentiation of cells in the megakaryocytic lineage and an increase in platelet production.
Problem associated with the failure of the facility's emergency power backup system(s) including generators and/or interruptible power systems (UPS).
Problem associated with the surrounding conditions in which the device is being used such as temperature, noise, lighting, ventilation, or other external factors such as power supply.
The orally available disodium salt form of eprodisate, a negatively charged sulfonated inhibitor of fibrillogenesis, that can be used in the treatment of amyloid A (AA) amyloidosis. Upon administration, eprodisate competitively binds to the glycosaminoglycan binding sites on serum amyloid A (SAA), which inhibits the formation of the glycosaminoglycan-amyloid fibril aggregate. This prevents the formation of amyloid deposits in certain organs, especially the kidneys, in AA amyloidosis.
Problem associated with a progressive loss of a material from a solid surface.
A device that does not consistently display the same message, result, reading, or image. e.g. the display might flicker, switch between readings or messages, or go completely blank for brief periods of time.
Problem associated with providing incorrect display information.
A biguanide derivative with hypoglycemic activity.
The hydrochloride salt form of etoformin, a biguanide derivative with hypoglycemic activity.
Problem associated with the device producing temperatures that are lower than specified.
A pathologic finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
Exocrine pancreatic cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Exocrine pancreatic cancer with distant metastasis. (from AJCC 6th Ed.)
Exocrine pancreatic cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Exocrine pancreatic cancer with no evidence of regional lymph node metastasis. (from AJCC 6th Ed.)
Exocrine pancreatic cancer with regional lymph node metastasis. (from AJCC 6th Ed.)
Exocrine pancreatic cancer with metastasis to a single regional lymph node. (from CAP Cancer of the Endocrine Pancreas Protocol- January 2005 Revision)
Exocrine pancreatic cancer with metastasis to more than one regional lymph node. (from CAP Cancer of the Endocrine Pancreas Protocol- January 2005 Revision)
Exocrine pancreatic cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th Ed.)
Exocrine pancreatic cancer with no evidence of a primary tumor. (from AJCC 6th Ed.)
Exocrine pancreatic cancer with tumor confined to the pancreas and 2 cm or less in greatest dimension. (from AJCC 6th Ed.)
Exocrine pancreatic cancer with tumor confined to the pancreas but more than 2 cm in greatest dimension. (from AJCC 6th Ed.)
Exocrine pancreatic cancer extending beyond the pancreas, but without involvement of the celiac axis or superior mesenteric artery. (from AJCC 6th Ed.)
Exocrine pancreatic cancer extending beyond the pancreas, involving the celiac axis or superior mesenteric artery and therefore unresectable. (from AJCC 6th Ed.)
Exocrine pancreatic cancer in which the primary tumor cannot be assessed. (from AJCC 6th Ed.)
Exocrine pancreatic cancer with a finding of carcinoma in situ, also known as grade III pancreatic intraepithelial neoplasia (PanIn III). (from AJCC 6th Ed.)
A small aggregate of cells found in adipose tissues, particularly those attached to the colon where the architectural details of the lymph node cannot be identified with certainty under the microscope. It may represent a lymph node completely replaced by metastatic cancer.
Problem associated with failure to move the device to an intended location.
Problem associated with a circuit, equipment, or system whereby its functions fail to be properly synchronized or its relative positions properly oriented.
Problem with the device not analyzing a signal.
Problem associated with the inability to backup or to retrieve a backed up version (corrupted file) of device data or system files.
Problem associated with lack or loss of adherence between materials intended to be joined together by an adhesive.
Problem associated with inability to initiate the appropriate charging process (e.g. of a battery or other charge storage device).
Problem associated with the inability of the device to allow a current of electricity to pass or to conduct electricity continuously along an electrical path.
Failure of the device therapy or set of therapies to terminate the harmful cardiac rhythm that the therapy is meant to terminate.
Problem associated with a failure to transition from a primary system, component, file, procedure to a backup in response to a failure in the primary item.
Inability of the device to make an incision, pierce or open as intended.
Problem associated with the device failing to complete a series of processes or events.
Problem associated with the failure of the device to deliver electrical energy intended to change an electrical rhythm.
Problem associated with the failure of the device to deliver any energy.
Problem associated with the inability of the medical device to be positioned in a specified location.
Problem associated with the failure of a battery or other charge storage device to appropriately discharge as intended. Does not apply to defibrillation.
Problem associated with the linking of the device whereby termination of the transfer of liquid, gas, electricity, or information cannot be accomplished, or linking components do not come apart, or disconnect, when expected.
Failure to properly disinfect the device during reprocessing.
Problem associated with failure of the device to discharge its load (e.g. surgical stapler failed to partially or completely deploy its staples).
Flushing process was not executed properly.
Problem associated with an undesired material change in the physical property of the device which is characterized by failure to fold.
Problem associated with the device failing to connect tissue with a stapling device due to the staples not forming correctly.
Failure (=complete nonperformance) with regard to the intended function of infusion.
Problem associated with the device failure to appropriately respond to signals from a system designed to interrogate its status.
The device does not collect or transfer the sample as intended.
Problem associated with the failure to see direct anchorage of an implant by the formation of bony tissue around the implant without the growth of fibrous tissue at the bone-implant interface.
Problem associated with the inability of the device to generate a therapeutic simulated heart beat via electrical impulses.
Problem associated with the device failing to begin the priming process (i.e. the process of preparation of device for the delivery of fluids).
Problem associated with the device which fails to start pumping.
Problem associated with a failure of the device to read a signal for interpretation or measurement.
Enzymatic cleaner was not removed properly from the device.
Problem associated with the failure of the device to select the appropriate input signal.
Problem associated with the failure of the device designed to respond to a physical stimulus (as temperature, illumination, motion) to transmit a resulting signal for interpretation or measurement.
Problem associated with the device or one of its components failing to detach or separate as intended.
Problem associated with the inability of the device to provide an appropriate or successful electrical shock.
Failure of the device to generate a correctly-shaped pacing output, e.g., a waveform that is too wide.
Device was not sterilized properly during reprocessing.
Problem associated with a failure of the device to transmit a record for interpretation or measurement.
Problem associated with the device providing incorrect alarm warning or alert to user.
Problem associated with the device incorrectly reporting that something has not been detected and may mislead the operator into not taking certain actions when action should be taken.
Problem associated with the device incorrectly reporting that something has been detected and may mislead the operator to take certain actions.
A finding about one or more characteristics of female reproductive system cancer, following the rules of the TNM AJCC v6 classification system.
Problem associated with the method or amount of time associated with the delivery of a fluid. Time to delivery or amount of delivered entity may be affected.
Problem associated with the combustion of the device with a steady flame.
The beginning of the first experience of the symptom complex of angina pectoris.
The beginning of the first occurrence of heart failure.
Problem associated with the connection of the device whereby channels, switching systems, and other functional units set up to provide means for a transfer of liquid, gas, electricity, or information do not match or fit.
Problem associated with the detachment of small pieces of the coating film of a material.
Problem associated with the device-related burn with an unsteady flame.
Problem associated with the amount of gas that is inspired and expired during one respiratory cycle.
A polychlorophenyl compound used as a topical antiseptic.
Escape (release, discharge) of fluid through an unintended location that is often accompanied by a loss of pressure and/or output.
The anilinoquinazoline derivative FEQA radiolabeled with the positron-emitting radioisotope fluorine F 18 with epidermal growth factor receptor (EGFR) binding and radioisotopic activities. Fluorine F 18 FEQA irreversibly binds to EGFR, allowing imaging of EGFR-positive tumor cells with positron emission tomography (PET).
A radiopharmaceutical consisting of the sodium salt of fluorine F 18 fluoride with radioisotopic and bone mineralizing activities. Fluoride binds to calcium ions in hydroxyapatite crystals in bone. The uptake and incorporation of positron-emitting fluorine F 18 fluoride into bone can be imaged using positron emission tomography (PET) or single-photon emission computed tomography (SPECT), allowing visualization of malignant bone lesions in which regional blood flow and bone turnover are increased.
Problem associated with the visibility of water vapor in the immediate atmosphere in which the device is being used.
Problem associated with contamination of a device with a chemical substance or other non biologic material.
Problem associated with a partial or full-thickness crack in the device materials.
Problem associated with the comprising materials having damaged edges.
Problem associated with uncontrolled flow of infusion of air, gas or fluids.
Problem associated with the visibility, odor, or toxicity of an ambient vapor or gas.
Problem associated with the visibility of molds, mildews, yeasts, and/or mushrooms in the immediate environment in which the device is being used.
A aminopteridine-based aldosterone antagonist with potassium-sparing diuretic activity. Furturene is able to antagonize aldosterone at the mineralocorticoid receptor in the kidneys, thereby increasing sodium excretion while inhibiting potassium excretion.
A clinical finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v6 classification system.
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of primary gallbladder cancer, following the rules of the TNM AJCC v6 classification system.
Gallbladder cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Gallbladder cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Gallbladder cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Gallbladder cancer with no regional lymph node metastasis. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with regional lymph node metastasis. (from AJCC 6th Ed.)
Gallbladder cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with tumor invading the lamina propria or muscle layer. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with tumor invading the lamina propria. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with tumor invading the muscle layer. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with tumor invading the perimuscular connective tissue and with no extension beyond the serosa or into the liver. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with tumor perforating the serosa (visceral peritoneum) and/or directly invading the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with tumor invading the main portal vein or hepatic artery, or invading two or more extrahepatic organs or structures. (from AJCC 6th and 7th Eds.)
Gallbladder cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
Problem associated with the unintended escape of a gas from the container in which it is housed.
A clinical finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v6 classification system.
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v6 classification system.
Gastric cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Gastric cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Gastric cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Gastric cancer with no evidence of metastasis to regional lymph nodes. (from AJCC 6th Ed.)
Gastric cancer with evidence of metastasis in 1-6 regional lymph nodes. (from AJCC 6th Ed.)
Gastric cancer with evidence of metastasis in 7-15 regional lymph nodes. (from AJCC 6th Ed.)
Gastric cancer with evidence of metastasis in more than 15 regional lymph nodes. (from AJCC 6th Ed.)
Gastric cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Gastric cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Gastric cancer with tumor invading the lamina propria or submucosa. (from AJCC 6th Ed.)
Gastric cancer with tumor invading the muscularis propria or subserosa. A tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum, without perforation of the visceral peritoneum covering these structures. In this case, the tumor is classified T2. If there is perforation of the visceral peritoneum covering the gastric ligaments or the omentum, the tumor should be classified T3. (from AJCC 6th Ed.)
Gastric cancer with tumor invading the muscularis propria. (from AJCC 6th Ed.)
Gastric cancer with tumor invading the subserosa. (from AJCC 6th Ed.)
Gastric cancer with tumor penetrating the serosa (visceral peritoneum) without invasion into adjacent structures of the stomach. (from AJCC 6th Ed.)
Gastric cancer with tumor invading into adjacent structures of the stomach which include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. Intramural extension into the esophagus or duodenum is classified by the depth of the greatest invasion in any of these sites, including the stomach. (from AJCC 6th Ed.)
Gastric cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Gastric cancer in situ with cancer cells confined within the glandular basement membrane (intraepithelial) and without invasion into the lamina propria. (from AJCC 6th and 7th Eds.)
An adverse event marked by rupture in the wall of a structure of the gastrointestinal system.
A finding about one or more characteristics of digestive system cancer, following the rules of the TNM AJCC v6 classification system.
Escape (release, discharge) of gel through an unintended location - as in leakage of ultrasound gel. Escape or release of gel from containment structures - as in gel filled implant leak.
A finding about one or more characteristics of genitourinary system cancer, following the rules of the TNM AJCC v6 classification system.
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v6 classification system.
Glottic cancer with no distant metastasis. (from AJCC 6th Ed.)
Glottic cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Glottic cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Glottic cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Glottic cancer with metastasis to a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Glottic cancer with metastasis to a single ipsilateral lymph node, more than 3 cm, but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Glottic cancer with metastasis in two or more ipsilateral nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Glottic cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Glottic cancer with metastasis in a lymph node, more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Glottic cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Glottic cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Glottic cancer with tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility. (from AJCC 6th and 7th Eds.)
Glottic cancer with tumor limited to one vocal cord. (from AJCC 6th and 7th Eds.)
Glottic cancer with tumor involving both vocal cords. (from AJCC 6th and 7th Eds.)
Glottic cancer with tumor extending to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. (from AJCC 6th and 7th Eds.)
Glottic cancer with tumor limited to the larynx with vocal cord fixation and /or invading paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex). (from AJCC 6th Ed.)
Glottic cancer with tumor invading through thyroid cartilage and/or invading tissues beyond the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 6th Ed.)
Glottic cancer with tumor invading prevertebral space, encasing carotid artery, or invading mediastinal structures. (from AJCC 6th Ed.)
Glottic cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Glottic cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
An organic chemical and ester of methacrylic acid. Glycol dimethacrylate is a reactive resin used as a functional monomer and a crosslinking agent in polymer production. Via photopolymerization, this agent is a component of hydrogels, which are used in applications such as scaffolds for tissue engineering or drug delivery carriers. In turn, hydrogel products can be applied to the prevention of thrombosis, post-operative adhesion formations, and as coatings for biosensors.
A chlorophenyl-containing sulfonylurea with hypoglycemic activity. Glyparamide rarely causes hepatic injury.
A second-generation sulfonylurea with antihyperglycemic activity. Glypinamide, also called azepinamide, is a chlorinated analogue of tolazamide.
A sulfonamide derivative with antihyperglycemic activity. Like sulfonylureas, glyprothiazol is able to lower blood glucose levels by increasing the release of insulin from pancreatic beta cells.
A sulfonamide derivative with antihyperglycemic activity. Like sulfonylureas, glysobuzole is able to lower blood glucose levels by increasing the release of insulin from pancreatic beta cells.
A rare malignant germ cell tumor arising from the testis and less often from the ovary. It is characterized by the presence of embryoid bodies which resemble early embryos.
An abnormality of gonadotropin production resulting in abnormal levels of circulating gonadotropin.
Problem associated with the increased rate of change in temperature, pressure, or other variables as a function of distance, time, etc.
Problem associated with the inability to connect conductors of an electronic system for the purpose of controlling or impeding ground currents and voltages.
A recombinant peptide chemically identical or similar to endogenous somatostatin. Somatostatin is a cyclic tetradecapeptide regulating many endocrine and nervous system functions. Somatostatin inhibits release of adenohypophyseal growth hormone, thyrotropin and corticotropin, pancreatic insulin and glucagon, gastric mucosal gastrin, intestinal mucosal secretin, and renal renin by binding to specific somatostatin receptors (SSTR), which are cell surface G protein-coupled receptors expressed in a tissue-specific manner.
A finding about one or more characteristics of head and neck cancer, following the rules of the TNM AJCC v6 classification system.
A nevus that arises from the skin in the head and neck region.
Heart failure which leads an individual to seek medical attention.
Problem related to increased battery internal impedance.
Problem associated with higher than intended electrical impedance levels between device and patient connections.
Reading provided by the device is too high or higher than expected.
Test results provided by the device are too high or higher than expected.
Problem associated with the amount of input required by the device to detect a signal being higher than expected/desired.
An event in the personal medical history of peripheral vascular disease as evidenced by: 1. Claudication either with exertion or at rest; 2. Amputation for arterial vascular insufficiency; 3. Aorto-iliac occlusive disease reconstruction, peripheral vascular bypass surgery, angioplasty or stent; or percutaneous intervention to the extremities; 4. Documented abdominal aortic aneurysm (AAA) repair or stent; 5. Positive non-invasive/invasive test. It does not include procedures such as vein stripping, carotid disease, or procedures originating above the diaphragm. (from NIH Roadmap Cardiovascular Data Standards Working Group)
A lymphocyte depleted Hodgkin lymphoma characterized by the presence of diffuse fibrosis and a few Hodgkin and Reed-Sternberg cells.
A lymphocyte depleted Hodgkin lymphoma characterized by the presence of reticular fibrosis.
A pan alpha-v human monoclonal antibody that recognizes alpha-v beta-1, alpha-v beta-3, alpha-v beta-5, and alpha-v beta-6 integrins with antiangiogenic and antitumor activities. Intetumumab competitively binds to and blocks both alpha-v beta-3 and alpha-v beta-5 integrins, resulting in inhibition of integrin-mediated tumor angiogenesis and tumor growth. Integrins facilitate the adhesion of stimulated endothelial cells to the extracellular matrix (ECM); trigger the secretion of ECM-rearranging proteases; and propagate signaling events that promote the survival and differentiation of cells in newly formed vasculature.
A serotonin antagonist and diuretic agent. Hydroxyindasate was never marketed.
Any substance that inhibits hydroxysteroid dehydrogenase, an enzyme that catalyzes the interconversion of hydroxyl and carboxyl groups on steroids, leading to activation or deactivation of the steroid molecule. Inhibition of hydroxysteroid dehydrogenase can be used as a treatment for esophageal ulceration and inflammation.
Contact of a tooth or restoration such that it encrouches on the interocclusal freeway space.
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
hypopharyngeal cancer, following the rules of the TNM classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v6 classification system.
Hypopharyngeal cancer with no distant metastasis. (from AJCC 6th Ed.)
Hypopharyngeal cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Hypopharyngeal cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with metastasis to a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with metastasis to a single ipsilateral lymph node, more than 3 cm, but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with metastasis in two or more ipsilateral nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with metastasis to one or more lymph nodes, more than 6 cm in greatest dimension. (from AJCC 6th Ed.)
Hypopharyngeal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with tumor limited to one subsite of the hypopharynx and with tumor size 2 centimeters or less in greatest dimension. (from AJCC 6th Ed.)
Hypopharyngeal cancer with tumor invading more than one subsite of hypopharynx or an adjacent site, or with tumor size more than 2 centimeters, but not more than 4 centimeters in greatest dimension without fixation of the hemilarynx. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with tumor size more than 4 centimeters in greatest dimension, or with fixation of the hemilarynx. (from AJCC 6th Ed.)
Hypopharyngeal cancer with tumor invading thyroid/cricoid cartilage, hyoid bone, thyroid gland, esophagus or central compartment soft tissue. (from AJCC 6ht Ed.)
Hypopharyngeal cancer with tumor invading prevertebral fascia, encasing carotid artery, or involving mediastinal structures. (from AJCC 6th Ed.)
Hypopharyngeal cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Hypopharyngeal cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
A proprietary agent with potential antineoplastic activity. IC83 appears to target cell cycle checkpoint/DNA repair enzymes, which are involved in the recognition and repair of damaged DNA and are overexpressed in many types of cancer cells. Inhibition of cell cycle checkpoint/DNA repair enzymes may enhance the cytotoxicity of DNA damaging agents and dissipate tumor cell resistance to chemotherapy and radiation therapy.
A novel proprietary small molecule, and a selective inhibitor of sonic hedgehog signaling pathway, with potential anti-tumor activity. The hedgehog signaling pathway is normally active during neuronal development in embryos and quiescent in adult cells. However, aberrant activation of the hedgehog pathway in adults has been implicated in many cancers, including cancers of the pancreas, prostate, lung (small cell), and brain (glioma). IPI-609 exerts its effect through inhibiting the hedgehog signaling pathway and thereby alters gene expressions of the cancer cells.
A substituted benzimidazole prodrug with selective and irreversible proton pump inhibitor activity. A weak base, ilaprazole accumulates in the acidic environment of the secretory canaliculus of the gastric parietal cell where it is converted to an active sulfenamide form that binds to cysteine sulfhydryl groups on the luminal aspect of the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting the pump's activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production.
Problem with image display leading to corrupted images or readouts/measurement indications.
Problem associated with electrical impedance levels between device and patient connections.
Problem associated with the device providing imprecise measurements when compared to a reference standard.
Problem associated with an unexpected or incomplete chemical reaction or effect.
Problem associated with the regulation and delivery of therapeutic agents (e.g. air, gas, drugs or fluids into a device or a patient under positive pressure).
Cardiac arrest which occurs in the hospital setting.
Complete failure to fill as part of an automated process. For insufficient filling use Short Fill. For excessive filling use Overfill. For inconsistent filling use Volume Accuracy Problem.
Failure (=complete nonperformance) with regard to the intended function of irrigation.
Delivery at endpoint not as intended; either too low or too high.
Problem associated with fluctuations in the flow volume delivered per time, even if end volume is correct, and delivered in the correct total time.
Problem associated with an error due to imperfect timing of two operations, e.g. signal transmission time.
Problem associated with the means by which the operator and the equipment communicate or interact.
Problem associated with a failure during any step of reprocessing process (cleaning, disinfection, packaging, labeling, sterilization) of a used or opened from its original packaging, but unused, device.
Pacing voltage or pulse width is less than desired.
Problem with audible messages which do not guide a device user to the correct action.
Problem associated with the inappropriate delivery of an electrical energy.
Inappropriate sinus tachycardia is a nonparoxysmal tachyarrhythmia characterized by an increased resting heart rate (HR) and/or an exaggerated HR response to minimal exertion or a change in body posture. HR is constantly above the physiological range with no appropriate relation to metabolic or physiological demands.
Problem associated with audible prompts which cannot be heard clearly.
A third-generation amino-bisphosphonate with anti-resorptive activity. Although the exact mechanism of action has yet to be fully elucidated, incadronic acid binds to and adsorbs onto hydroxyapatite crystals in the bone matrix, thereby preventing osteoclast resorption. This agent also binds to and inhibits farnesyl pyrophosphate synthase, an enzyme that plays an important role in the mevalonate pathway. This inhibits the formation of isoprenoids that are essential for protein prenylation. This prevents farnesylation and geranylgeranylation of proteins essential for osteoclast function, thereby leading to the induction of apoptosis of osteoclasts. By preventing osteoclast-mediated bone resorption, incadronic acid prevents bone destruction.
Problem associated with failure to process, service, or operate the device according to the manufacturer's recommendations or recognized best practices.
Problem with any deviation from the documented specifications of the device that relate to visual feedback. e.g. the display of information, images on a screen, or output from the device.
Problem associated with inaccuracies in any written, printed, or graphic matter that is affixed to the device or its packaging with any matter that accompanies the device including verbal instructions related to identification, technical description and use of the device provided by the device manufacturers that is intended for healthcare professionals.
Problem with the device inappropriately analyzing a signal.
Measurement obtained from or provided by the device is obviously incorrect.
Problem associated with the written program code or application software used by a device to calculate parameters other than those related to dose or power.
Problem associated with the device which has been used for an unapproved indication or for an unapproved intended use.
Unintended increase in pressure, compromising the device's intended function.
Problem associated with the removal of excess fluid or gas from a body cavity due to increased suction.
Unintended increase in pump speed and hence, probably, flow rate, compromising the intended function of the device.
A preparation of autologous peripheral blood mononuclear cells (PBMCs) radiolabeled with indium In 111 with radioisotopic activity. Autologous PBMCs are isolated, expanded ex vivo, radiolabeled with indium In 111, and then infused back into the patient. Gamma scintigraphy may then be used to image gamma ray-emitting indium In 111 PBMCs localized in lymphoma tissue.
A preparation of autologous peripheral polymorphonuclear (PMNLs) radiolabeled with indium In 111 with radioisotopic activity. Autologous PMNLs are isolated, expanded ex vivo, radiolabeled with indium In 111, and then infused back into the patient. Gamma scintigraphy may then be used to image gamma ray-emitting indium In 111 PMNLs localized in lymphoma tissue.
Problem associated with the inability of the device to expand or enlarge with the intended inflation agent (e.g. saline or air).
Problem associated with the device failing to deliver liquids or gases as intended (e.g. delivering drugs at incorrect rate, problems with drawing fluid from a system.)
Problem associated with unsatisfactory installation, configuration, and/or setup of a specific device.
Problem associated with device markings/labeling, instructions for use, training and maintenance documentation or guidelines.
Problem associated with the device insufficiently cooled in device active (working) or/and non-active (nonworking) state.
Problem associated with the device or its components producing temperatures that are not as high as what is specified.
Problem associated with the ineffective and inconsistent depolarization of the heart.
Problem associated with intermittent faults in electrical/electronic interconnections.
Problem associated with the infusion not being steady, characterized by intermittent stoppages to the flow.
Problem associated with the failure of pacing device for a limited period of time, following which the item recovers its ability to perform its required function without being subjected to any external corrective action. Note: such as failure is often recurrent.
Problem with the device receiving an incoming signal on an intermittent basis when expected to be continuous.
Problem associated with the failure to deliver shock for a limited period of time, following which the item recovers its ability to perform its required function without being subjected to any external corrective action. Note: such as failure is often recurrent.
A disease occurring chiefly in the connective-tissue framework of an organ.
A pathologic process that is confined to the mucosa.
A rare, unilateral, benign or malignant embryonic neoplasm typically presenting as a cilliary body mass during childhood. It is composed of medullary epithelial cells and heterologus elements, particularly cartilage, skeletal muscle, and brain tissue.
Problem associated with an undesired material change in shape, characterized by the infolding of one part within another part of a structure.
A benign epithelial neoplasm characterized by an endophytic growth, papillary pattern, and proliferation of neoplastic squamous cells without morphologic evidence of malignancy.
An electrocardiographic finding of a type of atrioventricular dissociation characterized by the atria (P waves) and ventricles (QRS complexes) beating at similar rates, although independently. (CDISC)
A morphologic finding indicating the presence of keratin in a tissue sample.
A topical preparation containing the antidepressant amitriptyline and the excitatory amino acid antagonist ketamine with potential topical analgesic activity. In addition to activating adenosine A1 receptors and inhibiting the neuronal reuptake of norepinephrine and serotonin, amitriptyline produces antinociceptive effects, which appear to be mediated through the modulation of multiple subtypes of glutamate receptors including the N-methyl D-aspartate (NMDA) receptor. Ketamine inhibits biogenic amine uptake, agonistically binds to mu-opioid receptors, and inhibits NMDA receptors. NDMA receptor antagonists such as amitriptyline and ketamine interfere with the role of NMDA receptors in the process of central sensitization in which NMDA receptors on spinal dorsal horn neurons are activated, resulting in an increase in synaptic efficacy and so an amplification of the response to sensory input.
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes. Laterality does not affect the N classification.
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v6 classification system. This classification system applies only to renal cell carcinoma; sarcomas and adenomas are not included.
Kidney cancer with no distant metastasis. (from AJCC 6th Ed.)
Kidney cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Kidney cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Kidney cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Kidney cancer with metastasis to a single regional lymph node. (from AJCC 6th Ed.)
Kidney cancer with metastasis to more than one regional lymph node. (from AJCC 6th Ed.)
Kidney cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
No evidence of primary tumor. (from AJCC 6th and 7th Eds.)
Kidney cancer with tumor 7 cm or less in greatest dimension, limited to the kidney. (from AJCC 6th and 7th Eds.)
Kidney cancer with tumor 4 cm or less in greatest dimension, limited to the kidney. (from AJCC 6th and 7th Eds.)
Kidney cancer with tumor more than 4 cm but not more than 7 cm in greatest dimension, limited to the kidney. (from AJCC 6th and 7th Eds.)
Kidney cancer with tumor more than 7 cm in greatest dimension, limited to the kidney. (from AJCC 6th and 7th Eds.)
Kidney cancer with tumor extending into major veins or invading the adrenal gland or perinephric tissues, but not extending beyond Gerota's fascia. (from AJCC 6th Ed.)
Kidney cancer with tumor directly invading the adrenal gland or perirenal and/or renal sinus fat, but not beyond Gerota's fascia. (from AJCC 6th Ed.)
Kidney cancer with tumor grossly extending into the renal vein or its segmental (muscle-containing) branches, or vena cava below the diaphragm. (from AJCC 6th Ed.)
Kidney cancer with tumor grossly extending into the vena cava above the diaphragm, or invading the wall of the vena cava. (from AJCC 6th Ed.)
Kidney cancer with tumor extending beyond Gerota's fascia. (from AJCC 6th Ed.)
Kidney cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
A finding associated with a patient based on the classification developed by Killip and Kimball, which classifies patients with myocardial infarction based on routine physical examination parameters, such as the presence or absence of rales, or a decreased systolic blood pressure.
An amino acid and herbal supplement with libido-enhancing activity. L-arginine/Korean ginseng/Ginkgo biloba/Damiana-based supplement contains a blend of the amino acid L-arginine and the herbs Korean ginseng, Ginkgo biloba, and damiana (Turnera aphrodisiaca) in addition to 14 other vitamins and minerals. The semi-essential amino acid L-arginine is a precursor for nitric oxide (NO); Korean ginseng may enhance the conversion of L-arginine into NO by NO synthase; and Ginkgo biloba may promote microvascular circulation. This agent may increase NO production, resulting in vasodilatation and an enhanced circulation critical to sexual function and arousal. The damiana component may exert an anxiolytic effect and stimulate sexual behavior.
The anhydrous, levorotatory isomer of a synthetic hydrazine derivative of the neurotransmitter dopamine. Carbidopa, a peripheral dopa decarboxylase inhibitor, is used as an adjunct with levodopa to prevent levodopa degradation to dopamine in extracerebral tissue, thereby decreasing the peripheral side effects of levodopa. Carbidopa does not penetrate the blood brain barrier; therefore, it does not interfere with the central nervous system (CNS) metabolism of levodopa to the active neurotransmitter dopamine which, in high concentrations in the brain, has anti-parkinsonian effects.
A catechin with the R configuration at C-2 and C-3.
The ionized form of lanthanum (trivalent ion) with phosphate binding property. Lanthanum ion binds dietary phosphate and inhibits the absorption of phosphate by forming highly insoluble lanthanum-phosphate complexes that reduce the concentrations of serum phosphate and calcium phosphate.
A finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v6 classification system.
A disorder characterized by bleeding from the larynx.
Problem associated with the escape of a liquid or gas from the vessel or container in which it is housed.
A levo isoform of leucovorin calcium with antineoplastic activity. Levoleucovorin is an active metabolite of folic acid, which does not require metabolism by dihydrofolate reductase. This agent counteracts the toxic effects of other folic acid derivative agents, rescuing the patient while permitting the antitumor activity of the folate antagonist. This agent also potentiates the effects of fluorouracil and its derivatives by stabilizing the binding of the drug's metabolite to its target enzyme, thus prolonging drug activity.
A synthetic levoisomer of thyroxine (T4), similar to the endogenous hormone produced by the thyroid gland. Thyroxine is de-iodinated to form triiodothyronine (T3) in the peripheral tissues. T3 enters the cell and binds to nuclear thyroid hormone receptors, and the hormone-receptor complex in turn triggers gene expression and produces proteins required in the regulation of cellular respiration, thermogenesis, cellular growth and differentiation, and metabolism of proteins, carbohydrates and lipids. T4 and T3 also possess cardiac stimulatory effect.
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v6 classification system.
Lip and oral cavity cancer with no distant metastasis. (from AJCC 6th Ed.)
Lip and oral cavity cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Lip and oral cavity cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with metastasis to a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with metastasis to a single ipsilateral lymph node, more than 3 cm, but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with metastasis in two or more ipsilateral nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with metastasis to one or more lymph nodes, more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with tumor size 2 centimeters or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with tumor size more than 2 centimeters, but not more than 4 centimeters in greatest dimension. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with tumor size more than 4 centimeters in greatest dimension. (from AJCC 6th and 7th Eds.)
Lip cancer with tumor invading through cortical bone, inferior alveolar nerve, floor of mouth or skin of face (i.e. chin or nose). Superficial erosion of bone or tooth socket by a gingival primary tumor is not sufficient to classify as T4. (from AJCC 6th Ed.)
Oral cavity cancer with tumor invading adjacent structures (e.g. through cortical bone, into deep [extrinsic] muscle of the tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face). (from AJCC 6th Ed.)
Lip and oral cavity cancer with tumor involving the masticator space, pterygoid plates, or skull base and/or encases the internal carotid artery. (from AJCC 6th Ed.)
Lip and oral cavity cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Lip and oral cavity cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
A rare disorder resulting from neoplastic exocrine excess. It is typically seen in 10-15 % of patients with pancreatic acinar cell carcinoma. Clinical signs include subcutaneous fat necrosis, polyarthralgia and osteolytic lesions. Clinical course may proceed to non-bacterial thrombotic endocarditis. Clinical prognosis is poor due to its usual onset with advanced disease.
A formulation of polyethylene glycol (PEG)-modified liposomes encapsulating the semisynthetic derivative of camptothecin irinotecan, with antineoplastic activity. As a prodrug, irinotecan is converted to the biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. In turn, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex of topoisomerase I and DNA, resulting in DNA breaks. This results in an inhibition of DNA replication and an induction of apoptosis. Pegylated liposomal delivery of irinotecan improves drug penetration into tumors and decreases drug clearance, thereby increasing the duration of exposure while lowering systemic toxicity.
A clinical finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v6 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, and biopsy.
A pathologic finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes. TNM pathologic regional lymph nodes findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v6 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A finding about one or more characteristics of primary liver cancer, following the rules of the TNM AJCC v6 classification system.
Liver cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Liver cancer with distant metastasis. (from AJCC 6th Ed.)
Liver cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Liver cancer with no regional lymph node metastasis. (from AJCC 6th Ed.)
Liver cancer with regional lymph node metastasis. (from AJCC 6th Ed.)
Liver cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th Ed.)
Liver cancer with no evidence of a primary tumor. (from AJCC 6th Ed.)
Liver cancer with a solitary tumor of any size without vascular invasion. (from AJCC 6th Ed.)
Liver cancer with a solitary tumor of any size with vascular invasion, or with multiple tumors none of which are more than 5 cm in size. (from AJCC 6th Ed.)
Liver cancer with multiple tumors at least one of which is more than 5 cm in size, or a tumor involving a major branch of the portal or hepatic vein. (from AJCC 6th Ed.)
Liver cancer with tumor(s) invading adjacent organs other than the gallbladder or with tumor perforating the visceral peritoneum. (from AJCC 6th Ed.)
Liver cancer in which the primary tumor cannot be assessed. (from AJCC 6th Ed.)
Problem associated with the connection of the device being loose or intermittent.
Problem associated with weakened integration of the device at the bone-implant interface due to loss of fibrous and/or bony tissue and leading to compromised anchorage of the device. i.e. 'Loosening/Lysis.'
Problem associated with the failure of primary power supplied by the facility.
Problem associated with the loss of the minimum amount of energy, voltage, or current needed to consistently stimulate the heart muscle.
The audible device alarm cannot be heard clearly.
Problem related to decreased battery internal impedance.
Problem associated with lower than intended electrical impedance levels between device and patient connections.
Reading provided by the device is too low or lower than expected.
Test results provided by the device are too low or lower than expected.
Problem associated with the amount of an input required by the device to detect a signal being lower than expected/desired.
A clinical finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v6 classification system.
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v6 classification system.
Lung cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Lung cancer with distant metastasis. (from AJCC 6th Ed.)
Lung cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Lung cancer with no evidence of metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Lung cancer with metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, including intrapulmonary nodes involved by direct extension of the primary tumor. (from CAP Lung Cancer Protocol--January 2005 Revision)
Lung cancer with metastasis to ipsilateral mediastinal and/or subcarinal lymph nodes. (from AJCC 6th and 7th Eds.)
Lung cancer with metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph nodes. (from AJCC 6th and 7th Eds.)
Lung cancer in which regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Lung cancer without any evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Lung cancer with a tumor size of 3 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (not invading the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1. (from AJCC 6th Ed.)
Lung cancer with a tumor size of greater than 3 cm in greatest dimension, or a tumor of any size extending into the main bronchus (2 cm or more distal to the carina), or a tumor of any size invading the visceral pleura, or a tumor with atelectasis or obstructive pneumonitis extending to the hilar region without involving the entire lung. (from AJCC 6th Ed.)
Lung cancer directly invading the chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura or parietal pericardium, or a tumor of any size extending into the main bronchus less than 2 cm distal to the carina but without involvement of the carina, or a tumor of any size with atelectasis or obstructive pneumonitis involving the entire lung. (from AJCC 6th Ed.)
Lung cancer with invasion of the mediastinum, heart, great vessels, trachea, esophagus, vertebral body or carina, or presence of separate tumor nodules within a same lobe, or the presence of a malignant pleural effusion. Although most pleural effusions associated with lung cancer are due to tumor, there are a few patients in whom multiple cytopathologic examinations of the pleural fluid are negative for tumor. In these cases, the fluid is non-bloody and is not an exudate. Such patients may be further evaluated with videothoracoscopy and direct pleural biopsy. When these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element. (from AJCC 6th Ed.)
Lung cancer in which the primary tumor cannot be assessed, or in which the diagnosis is confirmed by the presence of malignant cells in sputum or bronchial washings, but not visualized by imaging or bronchoscopy. (from AJCC 6th and 7th Eds.)
Lung cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
A neoplasm that arises from mature B-lymphocytes or plasma cells in the lung. Representative examples include bronchial mucosa-associated lymphoid tissue lymphoma, diffuse large B-cell lymphoma, lymphomatoid granulomatosis, and primary pulmonary plasmacytoma.
A radioimmunoconjugate consisting of the chimeric monoclonal antibody cG250 linked to the low energy beta-emitting radioisotope Lutetium 177, via the bifunctional macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA), with potential antineoplastic activity. The antibody moiety of lutetium Lu-177-DOTA-chimeric monoclonal antibody cG250 binds to renal cell carcinoma (RCC) cells expressing the RCC-associated antigen G250; a cytotoxic dose of beta radiation is selectively delivered to G250-expressing RCC cells upon internalization of the radioimmunoconjugate.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v6 classification system.
Major salivary gland cancer with no distant metastasis. (from AJCC 6th Ed.)
Major salivary gland cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Major salivary gland cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with metastasis in a lymph node, more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with tumor 2 cm or less in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with tumor more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with tumor more than 4 cm in greatest dimension, and/or tumor having extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. (from AJCC 6th and 7th Eds.)
Major salivary gland cancer with tumor invading the skin, mandible, ear canal, and/or facial nerve. (from AJCC 6th Ed.)
Major salivary gland cancer with tumor invading the skull base and/or pterygoid plates and/or encasing the carotid artery. (from AJCC 6th Ed.)
Major salivary gland cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
A gastrin-producing neuroendocrine tumor arising from the pancreas. It is characterized by inappropriate secretion of gastrin and associated with Zollinger Ellison syndrome. It displays vascular invasion and metastasizes to other anatomic sites.
A pancreatic neuroendocrine tumor producing vasoactive intestinal peptide (VIP). It is associated with watery diarrhea, hypokalemia, and hypochlorhydria or achlorhydria. It displays vascular invasion and metastasizes to other anatomic sites. One third of cases are metastatic at the time of diagnosis.
An aggressive neuroendocrine tumor located in the pancreas or small intestine. It is composed of cells containing vasoactive intestinal peptide. It is associated with watery diarrhea, hypokalemia, and hypochlorhydria or achlorhydria. It displays vascular invasion and metastasizes to other anatomic sites.
Problem associated with the device being positioned in a location other than intended or specified.
Problem associated with the acquisition of computer programming codes that can replicate and spread from one computer system to another thereby leading to damaged software, hardware and data.
Problem associated with any deviations from the documented specifications of the device that relate to nonconformity during manufacture to the design of an item or to specified manufacturing, packaging or shipping processes (out of box problem).
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v6 classification system.
Maxillary sinus cancer with no distant metastasis. (from AJCC 6th Ed.)
Maxillary sinus cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Maxillary sinus cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with metastasis to a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with metastasis to a single ipsilateral lymph node, more than 3 cm, but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with metastasis in a lymph node, more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with tumor invading anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. (from AJCC 6th Ed.)
Maxillary sinus cancer with tumor invading any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve, nasopharynx, or clivus. (from AJCC 6th Ed.)
Maxillary sinus cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Maxillary sinus cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
Problem associated with the incompatibility of the measurement systems between and/or within device systems that are inherent to the individual device thereby leading to miscalculated or mismatched measurements from those devices, e.g., international metric system versus U.S. measurement system.
The motion of the device is prevented or restricted.
Problem associated with the interaction between the patient's physiology or anatomy and the device that affects the patient and/or the device.
An accessory required for the intended purpose of the device appears incompatible with device, thus compromising the intended function of the device.
Problem associated with delayed or difficult activation of the device.
Problem associated with the movement of the device to an intended location.
Problem associated with the alarm system of the device.
Problem associated with the device setting a variable, register, or other storage location to an inappropriate or unexpected state.
Problem associated with the internal power of a device (e.g. battery, transformer, fuel cell or other power sources).
Problem associated with the operation of a device, related to its accuracy, and associated with the calibration of the device.
Problem associated with the inability of a device to successfully charge an electrical source.
Problem related to an obstruction or blockage within the device component (e.g. tube, opening, pipe) that results in no flow.
A component required for the proper functioning of a device is not compatible with other components or subassemblies of a device, thus compromising the intended function of a device.
A device component(s) found to be missing when delivered to the user facility.
Problem associated with the incompatibility of any device while being operated in the same use environment thereby leading to a dysfunction between the devices.
Problem associated with the presence of any unexpected foreign substance found on the surface or in the package materials, which may affect optimal performance for its intended use.
Problem associated with the undesired introduction of impurities either chemical or microbiological in nature, or of foreign matter into or onto a device at the user facility.
Problem associated with the undesired presence of body fluid in/on the device, which are not part of the documented device specifications and requirements.
Problem associated with packaging or shipping damage prior to the use of a device.
Problem associated with a device being received in such a manner to indicate that its sterility has been compromised (e.g. sterile packaging breached, visible contaminate present).
Problem associated with any deviations from the documented specifications of a medical device that relate to the sequence of events for activation, positioning or separation of device.
The device that is difficult to flush, possibly indicating an obstruction within device.
Problem associated with the use of the device in terms of user experiencing difficulty opening and closing the device, even if the operation is being performed according to labeled instructions for use.
Problem associated with the use of the device in terms of user experiencing difficulty in preparing device for use, even if the operation is being performed according to labeled instructions for use.
Problem associated with a failure of the electrical circuitry of the device.
Problem associated with an unexpected or inappropriate smell released by the device.
Problem associated with a cloud of vapor or gas generated from the device, generally associated after a fire or a burn.
Problem with the device's intended output of energy.
Problem associated with the energy output from the device not being in the expected part of the spectrum.
Problem associated with errors in identification of expiration date.
Problem associated with the feature that prevents the unsafe use of the device.
Problem associated with the inability of device to turn itself off when the device is not in an operable condition.
Problem associated with the failure of the device to perform a self-calibration procedure or process designed to assure the accuracy and proper performance of the device.
Problem associated with the inability of the device to turn on related to energy delivered to a medical device.
Problem associated with the device failing to set a variable, register, or other storage location back to a prescribed state.
Problem associated with the device failing to operate when not connected to a fixed power source.
Problem associated with the device failing to perform an internal self-diagnostic process to ensure normal operation during or prior to use.
Problem associated with the device not powering off when a shut down was requested.
Problem associated with the device failing to set a variable, register, or other storage location back to zero.
Problem associated with the process of passing a substance through a porous medium, e.g., a blood clot filter for the removal of suspended matter.
Problem associated with the filter failing to remove items or substances which should have been removed.
Problem associated with compatibility between device, patients or substances (medication, body fluid, etc.).
Problem associated with any deviations from the documented specifications of the device that relate to any ingredient or reagent characterization.
pH higher than expected and/or anticipated.
Problem associated with the written, printed or graphic material accompanying or affixed to the device or any of its packaging. This includes verbal instructions relating to identification, technical description, and usage provided by a medical device manufacturers. Problems can include but are not limited to this material being unclear, missing, worn out, incorrect or inaccurate.
Problem associated with undesired damage or breakage of those materials used in the device construction.
Problem associated with the pressure inside a vessel or container rising to such a degree that the container ruptures.
Problem associated with an undesired partial separation and/or a visible opening along the length or width in the materials that are used in the device construction.
Problem associated with a undesired change in the chemical structure, physical properties, or appearance in the materials that are used in the device construction.
Problem associated with small pieces of the device breaking off unexpectedly.
Problem associated with any deviations from the documented specifications of the device that relate to the limited durability of all material used to construct the device.
Material constituting device is perforated possibly compromising the device's intended purpose.
Device material(s) punctured leading to undesired holes/openings.
Problem associated with perforations that lead to bursting of the device.
Problem associated with an undesired disassociation or breaking apart of the device.
Problems associated with mechanical actions or defects of the device, which includes any moving parts or subassemblies, etc.
Problem associated with a device mechanical functioning of machinery, moving parts or tools of device being changed or modified.
Problem associated with incorrect assembly of the device or constituents after being put into use.
A device found incorrectly assembled when delivered to the user facility.
Problem associated with transmission of visible light affecting the quality of the image transmitted or otherwise affecting the intended application of the visible light path.
Problem associated with any deviation from the documented specifications of the device that relate to the end result, data, or test results provided by the device.
Device output is exceeding the documented specifications of the device.
Device output is below the documented specifications of the device.
Problem associated with the nonconformance to the device specifications due to incomplete or missing packaging that may compromise the device operation as intended.
Problem associated with the materials used to construct the cover or outer wrapping of the device.
Problem associated with the application of a force either internal or external to device that compromises the flow of fluid or gas.
Problem associated with any deviations from the documented specifications of the device that relate to the implemented and inherited design features specific to devices used for reducing risks to patient or caregiver or maintaining risks within specified levels.
Problem associated with the device continuing to be in an active state after deactivation was requested.
Problem associated with setting a variable, register, or other storage location back to a prescribed state.
Problem associated with drawing back the device to an intended location.
Problem associated with shipping damage or problem prior to the use of the device.
Problem associated with the basic physical construction or physical make up of the device.
Problem associated with the device producing unintended temperatures.
Problem associated with the inability of the device to stay in an upright position.
Problem associated with linking of a device and/or the functional units set up to provide means for a transfer of liquid, gas, electricity or data.
Problem associated with one device causing harm to another device.
Problem associated with the comprising materials' deformation in that device fails to open its wrapping or open/extend in a certain manner i.e. balloon or lens.
A difficulty with the quality of part of the device or the device itself.
The physical size and/or shape of the device was inadequate with regard to the patient's anatomy.
Issue associated with the inability to retrieve device and/or device fragments during medical procedures.
Problem associated with any from the documented specifications of a device that relate to any chemical characterization, i.e., element, compound, or mixture.
A beta-adrenergic receptor agonist with tocolytic activity. Meluadrine binds to and activates beta-2 adrenergic receptors of myometrial smooth muscle in the uterus, thereby activates adenyl cyclase, an enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increased cAMP levels leads to a reduction in intracellular calcium concentration, thereby causes smooth muscle relaxation and decreases the intensity of uterine contractions.
The anhydrous form of mercaptopurine, a thiopurine-derivative antimetabolite with antineoplastic and immunosuppressive activities. Produced through the metabolism of mercaptopurine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT), mercaptopurine metabolites 6-thioguanosine-5'-phosphate (6-thioGMP) and 6-thioinosine monophosphate (T-IMP) inhibit nucleotide interconversions and de novo purine synthesis, thereby blocking the formation of purine nucleotides and inhibiting DNA synthesis. This agent is also incorporated into DNA in the form of deoxythioguanosine, which results in the disruption of DNA replication. In addition, mercaptopurine is converted to 6-methylmercaptopurine ribonucleoside (MMPR) by 6-thiopurine methyltransferase; MMPRs are also potent inhibitors of de novo purine synthesis.
A morphologic finding that refers to the transformation or replacement of a group of non-mesenchymal cells into osseous, cartilagenous, or lipomatous cells.
Transformation of malignant cells with a specific differentiation to different morphologic types.
A signet ring cell carcinoma which has spread from its original site of growth to another anatomic site.
A nonpeptide angiotensin II receptor antagonist with antihypertensive activity. Milfasartan selectively competes with angiotensin II for the binding of the angiotensin II (AT1) receptor subtype 1 in vascular smooth muscle, thereby blocking angiotensin II-mediated vasoconstriction resulting in vascular dilatation. In addition, the antagonistic effect on AT1 in the adrenal gland, prevents angiotensin II-induced stimulation of aldosterone synthesis and secretion by the adrenal cortex. This blocks the effects of aldosterone leading to an increase in sodium excretion and water and eventually a reduction in plasma volume and blood pressure.
A morphologic finding indicating the infiltration of the stroma immediately adjacent to a carcinoma in situ by isolated malignant cells or small groups of malignant cells.
A lesion in which the neoplastic epithelial cells invade into but not through the capsule that surround the neoplasm, or invade the entire thickness of the capsule, or invade vessels surrounding the capsule. Unlike widely invasive lesions, the minimally invasive lesions cannot be recognized as carcinomas on clinical and surgical grounds. The diagnosis can only be established microscopically.
Problem associated with the written program code or application software used by a device for calculations related to device power.
Problem associated with the connection of the device being improper or not in accordance with device specification, requirements or intended uses.
Issue associated with failure of device to discharge its load (e.g., surgical stapler failed to partially or completely deploy its staples).
The problem relates to the poor focusing of the object or the focus is on the wrong object or in the wrong area.
A nucleotoxic with potential antineoplastic activity. The mechanism of action through which mitotenamine exerts its effect has yet to be fully elucidated.
A microsomal triglyceride transfer protein inhibitor, approved in veterinary use for weight loss and reduction of hyperlipidemia in dogs.
Problem associated with damage inflicted upon the device from water vapor or water in the immediate environment in which the device is being used.
Problem associated with an unsatisfactory humidity level in the storage or use environment which affects the device performance.
Problem associated with a solid device being transformed into a molten or liquid state.
The most recent occurrence of angina pectoris.
The most recent occurrence of heart failure.
A low malignant potential adenofibroma of the ovary It is characterized by an atypical epithelial hyperplasia. The epithelial cells contain intracytoplasmic mucin. There is no evidence of stromal destructive invasion.
A solid, sharply demarcated, benign or malignant nodular mass that is attached to the wall of an organ.
A phenylretinamide and synthetic retinoid analogue. N-(2-carboxyphenyl)retinamide may bind to and activate retinoic acid receptors (RARs), thereby inducing changes in the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.
A phenylretinamide and synthetic retinoid analogue. N-(4-ethoxyphenyl)retinamide may bind to and activate retinoic acid receptors (RARs), thereby inducing changes in the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.
A phenylretinamide and synthetic retinoid analogue. N-(4-hydroxyphenyl)-9-cis-retinamide may activate retinoic acid receptors, thereby altering the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.
An ethylretinamide and synthetic retinoid analogue. N-(ethyl)-9-cis-retinamide may activate retinoic acid receptors, thereby altering the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v6 classification system.
Nasal cavity and ethmoid sinus cancer with no distant metastasis. (from AJCC 6th Ed.)
Nasal cavity and ethmoid sinus cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Nasal cavity and ethmoid sinus cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with metastasis to a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with metastasis to a single ipsilateral lymph node, more than 3 cm, but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with metastasis in a lymph node, more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with tumor restricted to any one subsite, with or without bony invasion. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with tumor invading any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. (from AJCC 6th Ed.)
Nasal cavity and ethmoid sinus cancer with tumor invading any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than the maxillary division of the trigeminal nerve, nasopharynx, or clivus. (from AJCC 6th Ed.)
Nasal cavity and ethmoid sinus cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Nasal cavity and ethmoid sinus cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
A finding about one or more characteristics of nasal cavity and paranasal sinus cancer, following the rules of the TNM AJCC v6 classification system.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v6 classification system.
Nasopharyngeal cancer with no distant metastasis. (from AJCC 6th Ed.)
Nasopharyngeal cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Nasopharyngeal cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Nasopharyngeal cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Nasopharyngeal cancer with unilateral metastasis to one or more lymph nodes, 6 cm or less in greatest dimension, above the supraclavicular fossa. Midline nodes are considered ipsilateral nodes. (from AJCC 6th Ed.)
Nasopharyngeal cancer with bilateral metastasis to one or more lymph nodes, 6 cm or less in greatest dimension, above the supraclavicular fossa. Midline nodes are considered ipsilateral nodes. (from AJCC 6th Ed.)
Nasopharyngeal cancer with metastasis to one or more lymph nodes greater than 6 cm and/or to lymph nodes which are whole or in part in the supraclavicular fossa. (from AJCC 6th Ed.)
Nasopharyngeal cancer with metastasis to one or more lymph nodes greater than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Nasopharyngeal cancer with metastasis to lymph nodes which are whole or in part in the supraclavicular fossa. This includes caudal portions of Levels IV and V lymph nodes. All cases with lymph nodes (whole or in part) in the supraclavicular fossa are considered N3b. (from AJCC 6th Ed.)
Nasopharyngeal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Nasopharyngeal cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Nasopharyngeal cancer with tumor confined to the nasopharynx. (from AJCC 6th Ed.)
Nasopharyngeal cancer with tumor extending into the soft tissue. (from AJCC 6th Ed.)
Nasopharyngeal cancer with tumor extending into the oropharynx and/or nasal cavity without parapharyngeal extension. (from AJCC 6th Ed.)
Nasopharyngeal cancer with parapharyngeal extension. Parapharyngeal extension denotes posterolateral infiltration of tumor beyond the pharyngobasilar fascia. (from AJCC 6th Ed.)
Nasopharyngeal cancer with tumor involving bony structures and/or paranasal sinuses. (from AJCC 6th Ed.)
Nasopharyngeal cancer with intracranial extension and /or involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space. (from AJCC 6th Ed.)
Nasopharyngeal cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Nasopharyngeal cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
Problem associated with material damage to a surface, usually involving progressive loss or displacement of material, due to relative motion between that surface and a contacting substance or substances.
A broad classification for disorders in which the development of neoplasms typically occur in association with a characteristic set of signs or symptoms. These disorders may be inherited or acquired.
A third-generation, aminohexane bisphosphonate with anti-resorptive and anti-hypercalcemic activities. Although the exact mechanism of action has yet to be fully elucidated, neridronic acid binds to and adsorbs onto hydroxyapatite crystals in bone matrix, thereby preventing osteoclast resorption. This agent also binds to and inhibits farnesyl pyrophosphate synthase, an enzyme that plays an important role in the mevalonate pathway. This inhibits the formation of isoprenoids that are substrates for protein prenylation. This prevents farnesylation and geranylgeranylation of proteins essential for osteoclast function, thereby leading to the induction of apoptosis of osteoclasts. By preventing osteoclast-mediated bone resorption, neridronic acid decreases bone turnover rate, stabilizes the bone matrix and reduces hypercalcemia.
An immunophenotypic test result indicating positive staining of neoplastic cells for neuron-specific enolase.
A genetic disorder characterized by defective polymorphonuclear cell actin function, resulting in impaired granulocyte motility.
An absolute neutrophil count (ANC) of 500 or more (500 or more neutrophils in a cubic millimeter of blood) for 3 days in a row is a sign of engraftment. Neutrophil engraftment can occur as early as 10 days after transplant. About 20 days is more common for patients who receive marrow or peripheral (circulating) blood cells. For patients who receive cord blood, the average time to neutrophil engraftment is between 21 and 35 days.
A finding associated with a patient based on the functional classification developed by the New York Heart Association (NYHA), for categorizing patients with defined or presumed cardiac disease. The classification system is based on the ability, or lack thereof, to engage in physical activity. The classification system comprises four classes, though NYHA Class III and Class IV are often aggregated for the purpose of outcomes analysis.
A finding associated with a patient with defined or presumed cardiac disease without limitations of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea. (from The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.)
A finding associated with a patient with defined or presumed cardiac disease with slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, or dyspnea. (from The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.)
A finding associated with a patient with defined or presumed cardiac disease with marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. (from The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.)
A finding associated with a patient with defined or presumed cardiac disease with inability to carry on any physical activity without discomfort. Symptoms are present even at rest or minimal exertion. (from The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.)
A device problem is not adequately described by any other term. Note: this code must not be used unless there is no other feasible code.
Problem associated with the absence of display or image.
The device that does not have a fail-safe mechanism, although such mechanism would be required for its appropriate and/or safe functioning.
Problem arising from the device failing to deliver the specified liquid or gas.
Problem associated with no measurement outcome, value or data obtained from the device.
Unintended complete loss of pressure, compromising the device's intended function.
Problem associated with the device ceasing to provide audible prompts.
An acquired non-neoplastic disorder characterized by marked reduction or absence of megakaryocytes and thrombocytopenia.
A disorder that affects the small or large intestine and is non-neoplastic in nature. Representative examples include acute appendicitis, colitis, and inflammatory bowel disease.
A non-neoplastic disorder that affects the stomach. Representative examples include gastritis and ulcer.
An abnormal tissue change in a tooth that does not involve caries.
An electrocardiographic finding of a widened QRS duration typically greater than 110 ms which does not meet the morphologic criteria for any of the standard bundle branch or fascicular block patterns. (CDISC)
Problem associated with the device that does not meet the specifications or requirements for which it was manufactured (e.g. materials, parts, manufacturing process).
Problem related to an obstruction or blockage within the device component (e.g. tube, opening, pipe) that results in restriction of flow.
A Fc-modified, humanized monoclonal antibody directed against the B-cell CD20 cell surface antigen, with immunosuppressive activity. Ocrelizumab binds to CD20 on the surfaces of B-cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B-cells overexpressing CD20. The CD20 antigen, a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel, is found on over 90% of B-cells, B-cell lymphomas, and other lymphoid tumor cells of B-cell origin; it plays an important role in B-cell functioning.
The beginning of the experience of the symptom complex of angina pectoris.
Problem associated with an undesirable opaqueness or cloudiness.
Problem associated with malfunction of the computer operating system as opposed to an application software problem.
Problem associated with replacing an older operating system to an up-to-date operating system.
Problem associated with being off-center of optical lenses.
Problem associated with an undesired change of color.
Problem associated with an optical defect in an image-forming system whereby the image is not the shape of an ideal image of the object.
Problem associated with the blocking of optical devices, e.g. visual pathways.
An orally active derivative of the short-chain fatty acid butyrate with potential antineoplastic activity. 4-Phenylbutyrate inhibits histone deacetylase, resulting in cell cycle gene expression modulation, reduced cell proliferation, increased cell differentiation, and apoptosis. This agent also initiates fragmentation of genomic DNA, resulting in decreased DNA synthesis and the inhibition of tumor cell migration and invasion.
Problem associated with an incorrect image orientation on the device display.
A pathologic finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v6 classification system.
Oropharyngeal cancer with no distant metastasis. (from AJCC 6th Ed.)
Oropharyngeal cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Oropharyngeal cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with metastasis to a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with metastasis to a single ipsilateral lymph node, more than 3 cm, but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with metastasis in two or more ipsilateral nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with metastasis to one or more lymph nodes, more than 6 cm in greatest dimension. (from AJCC 6th Ed.)
Oropharyngeal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with tumor size 2 centimeters or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with tumor size more than 2 centimeters, but not more than 4 centimeters in greatest dimension. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with tumor size more than 4 centimeters in greatest dimension. (from AJCC 6th Ed.)
Oropharyngeal cancer with tumor invading the larynx, deep/extrinsic muscle of tongue, medial pterygoid muscles, hard palate, or mandible. (from AJCC 6th Ed.)
Oropharyngeal cancer with tumor invading the lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery. (from AJCC 6th Ed.)
Oropharyngeal cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Oropharyngeal cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
Problem associated with interconnection between the bone tissue and the implanted device.
A benign neoplasm of the kidney occurring in infants. It develops as an intracalyceal mass and is characterized by the presence of osteoid formation, osteoblast-like cells, and spindle cells.
A clinical finding about one or more characteristics of ovarian cancer, following the rules of the TNM AJCC v6 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, biopsy or laboratory testing.
A pathologic finding about one or more characteristics of ovarian cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of ovarian cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of ovarian cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of ovarian cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of ovarian cancer, following the rules of the TNM AJCC v6 classification system.
Ovarian cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Ovarian cancer with distant metastasis, excluding peritoneal metastasis. (from AJCC 6th Ed.)
Ovarian cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Ovarian cancer without involvement of regional lymph nodes. (from AJCC 6th Ed.)
Ovarian cancer with metastasis to one or more regional lymph nodes. (from AJCC 6th Ed.)
Ovarian cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th Ed.)
Ovarian cancer with no evidence of a primary tumor. (from AJCC 6th Ed.)
Ovarian cancer with tumor confined to one or both ovaries. (from AJCC 6th Ed.)
Ovarian cancer with tumor in one ovary with capsule intact, no tumor on ovarian surface and no malignant cells in either ascites or peritoneal washings. The presence of ascites does not affect staging unless malignant cells are present. (from AJCC 6th Ed.)
Ovarian cancer with tumor in both ovaries with capsule intact, no tumor on ovarian surface and no malignant cells in either ascites or peritoneal washings. The presence of ascites does not affect staging unless malignant cells are present. (from AJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with either a ruptured capsule, or tumor on the ovarian surface, or presence of malignant cells in either ascites or peritoneal washings. (from AJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with pelvic extension and/or implants. (from AJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with extension or implants on uterus and/or fallopian tubes and without malignant cells in ascites or peritoneal washings. (from AJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with extension or implants on pelvic tissues other than the uterus or fallopian tubes, and without malignant cells in ascites or peritoneal washings. (from AJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with extension or implants on the uterus and/or fallopian tubes, or other pelvic tissues, with malignant cells in either ascites or peritoneal washings. (from AJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with microscopic or macroscopic peritoneal metastasis beyond the pelvis. (from ACJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with microscopically confirmed peritoneal metastasis beyond the pelvis. (from AJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with macroscopic peritoneal metastasis beyond the pelvis, with tumor size of 2 cm or less in greatest dimension. (from AJCC 6th Ed.)
Ovarian cancer involving one or both ovaries with macroscopic peritoneal metastasis beyond the pelvis, with tumor size of more than 2 cm in greatest dimension. (from AJCC 6th Ed.)
Ovarian cancer in which the primary tumor cannot be assessed. (from AJCC 6th Ed.)
A sex cord-stromal tumor of the ovary. Thecomas range from small tumors to large solid or solid-cystic masses of up to 15 cm. They are unilateral in over 90 percent of cases and are rarely malignant. Thecomas are stromal tumors made up of cells that resemble theca cells, lutein cells and fibroblasts. They are traditionally classified within the sex cord-stromal tumor category of ovarian tumor types.
Excessive filling of a device. For complete failure to fill use inability to auto-fill. For insufficient filling use Short Fill. For inconsistent filling - use Volume Accuracy Problem.
Problem associated with the device producing high temperatures, such that its operation is compromised or harm is caused (e.g. overheating that produces melting of components or automatic shutdown).
Problem associated with a delivery overdose of therapeutic agents, such as drugs or fluids being delivered into a device or a patient.
A necrotizing arteritis that exhibits characteristic features of several distinct vascular disorders.
Problem related to failure of the device to properly filter cardiac signals resulting in inappropriate device response.
A water soluble, orally available, dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist with hypoglycemic activity.
An aurora kinase inhibitor with potential antineoplastic activity. PF-03814735 binds to and inhibits aurora kinases, serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis. Inhibition of aurora kinases may result in an inhibition of cellular division and proliferation in tumor cells that overexpress aurora kinases.
A cancer vaccine consisting of a DNA plasmid encoding epitopes of the human preferential antigen of melanoma (PRAME) and the prostate specific membrane antigen (PSMA) with potential immunostimulating activity. Upon direct administration of this vaccine into lymph nodes, peptides expressed by DNA plasmid vector pPRA-PSM may activate the immune system, resulting in a cytotoxic T-lymphocyte (CTL) response against PRAME- and PSMA-expressing cells. PRAME and PSMA are tumor associated antigens upregulated in a number of cancer cell types. As part of the MKC1106-PP regimen exploiting the 'prime-boost strategy', this plasmid is responsible for priming the immune response and is used in conjunction with a peptide vaccine consisting of PRAME and PSMA that boosts the immune system against PRAME- and PSMA-expressing tumor cells.
The sodium salt form of palmoxirate, an inhibitor of long-chain fatty acid oxidation with hypoglycemic activity. By inhibiting fatty acid oxidation, palmoxirate increases carbohydrate oxidation attributed to the glucose-fatty acid cycle (Randle cycle) resulting in decreased blood glucose levels.
A benign or malignant neuroendocrine tumor that arises from the pancreas and secretes pancreatic polypeptide.
A broad spectrum imidazole derivative with antifungal activity. Although the exact mechanism of action has yet to be fully elucidated, parconazole, like other azole antifungals, most likely inhibits the cytochrome P450 dependent 14 alpha demethylation of lanosterol. This prevents the synthesis of ergosterol which is a crucial component of the fungal cell membrane. By disrupting fungal cell membrane synthesis and integrity, parconazole alters fungal cell membrane permeability, promotes loss of essential intracellular components and eventually inhibits fungal cell growth.
The hydrochloride salt form of parconazole, a broad spectrum imidazole derivative with antifungal activity. Although the exact mechanism of action has yet to be fully elucidated, parconazole, like other azole antifungals, most likely inhibits the cytochrome P450 dependent 14 alpha demethylation of lanosterol. This prevents the synthesis of ergosterol which is a crucial component of the fungal cell membrane. By disrupting fungal cell membrane synthesis and integrity, parconazole alters fungal cell membrane permeability, promotes loss of essential intracellular components and eventually inhibits fungal cell growth.
An electrocardiographic finding of the sudden onset of transient AV block, which is often associated with preexisting conduction disorders. (CDISC)
Substances that consist of separate particles that are introduced by the device during use.
The hydrochloride salt of a small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated.
Death of a fetus, neonate, or patient 20 years or younger.
A (2-chloroethy1)nitrosourea compound with antineoplastic activity. Petamustine was never marketed.
Problem associated with the escape of blood around a heart valve, particularly around its leaflets.
A morphologic finding indicating the presence of a non-neoplastic or neoplastic lymphocytic infiltrate surrounding vessels.
A finding about one or more characteristics of pharyngeal cancer, following the rules of the TNM AJCC v6 classification system.
Any natural or synthetic substance that inhibits the activity of any phase I metabolic enzyme. The cytochrome P450 (CYP450) mono-oxygenase family of enzymes catalyzes the majority of the phase I reactions. CYP450 enzymes oxidize xenobiotics, especially drugs and carcinogens, as well as certain endogenous substances. This leads to the introduction of a polar functional group to the compound, enhances their water solubility and renal excretion. However, a highly reactive intermediate and more toxic metabolite than the parent molecule may be produced that can potentially react with and damage DNA. The main CYP450 enzymes involved in the activation of carcinogens include CYP1A1, -1A2, -2A6, -2E1 and -3A4. Phase I enzymes inhibitors prevent the biotransformation of many pro-carcinogens to activated mutagens and carcinogens.
Problem associated with the corrosion of a material's surface, confined to a point or small area that takes the form of cavities.
An angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Upon hydrolysis, the free SH metabolite of pivopril competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Pivopril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A platelet count of 20,000 to 50,000 (platelets per microliter of blood) is a sign of platelet engraftment. For patients who receive marrow or peripheral blood cells, platelet engraftment often happens at the same time or a little bit after neutrophil engraftment. For patients who receive cord blood, it may be 8 weeks or longer after transplant before platelet engraftment occurs.
Problem associated with a pocket of skin in which the pulse generator is housed.
Any substance that inhibits Poly (ADP-Ribose) polymerase, an enzyme involved in detecting DNA single strand breaks and the initiation of DNA repair. Inhibition of Poly (ADP-Ribose) polymerase has direct cytotoxic effects by inhibiting DNA repair and causing cell death.
Juvenile rheumatoid arthritis affecting multiple joints, usually symmetrically. It may be associated with low grade fever, anemia, and weight loss. Patients usually test negative for rheumatoid factor.
A proprietary formulation composed of a defined, decaffeinated green tea extract, containing polyphenolic flavonol catechins, isolated from the plant Camellia sinensis with antiviral, antioxidant, and potential chemopreventive activities. The primary catechins found in green tea are epicatechin (EC), epigallocatechin (EGC), epicatechin-3 gallate (ECG), and epigallocatechin-3-gallate (EGCG), the most potent. As potential chemopreventive agents, catechins scavenge free radicals; inhibit enzymes involved in cell replication and DNA synthesis; interfere with cell-to-cell contact adhesion; and inhibit various intracellular communication pathways required for cell division. In addition, it has been postulated that EGCG may trap growth factors such platelet-derived growth factor (PDGF) on cell membranes, immobilizing growth factors on cell membranes and preventing ligand-receptor crosslinking and growth factor receptor activation.
Inadequate quality of an image or any visual representation displayed by the device, or output from the device.
Problem associated with the separation of solid particles from a liquid as the result of a chemical or physical change.
The phosphate ester form of prednisolone, a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. As a glucocorticoid receptor agonist, prednisolone 21-phosphate binds to specific intracellular glucocorticoid receptors, and causes the ligand-receptor complex to be translocated to the nucleus where it initiates the transcription of glucocorticoid-responsive genes such as various cytokines and lipocortins. Lipocortins inhibit phospholipase A2, thereby blocking the release of arachidonic acid from membrane phospholipids and preventing the synthesis of prostaglandins and leukotrienes, both potent mediators of inflammation. This agent also decreases the number of circulating lymphocytes, induces cell differentiation, and stimulates apoptosis in sensitive tumor cell populations.
Problems with the early or unexpected activation of the elective replacement indicator.
Problems with the activation of a protective measure indicator earlier than expected.
Battery discharging earlier than expected.
Problem associated with early and unexpected activation of the device.
Problem associated with the use of the device in terms of nonconforming to that device's intended use, specifications, procedure and process or service instructions and information provided by the device manufacturers.
A morphologic finding that indicates the presence of a substantial neoplastic cellular proliferation within a ductal structure.
Problem with visual messages which continue to be displayed on/by the device after the appropriate action has been taken.
Problem associated with pump performance deviating from specifications in a way to compromise flow or infusion.
Unexpected /unintended cessation of pump.
The sodium salt form of pyrithione, a fungistatic and antimicrobial derivative of aspergillic acid. Although the exact mechanism of action remains to be fully elucidated, pyrithione sodium appears to interfere with membrane transport ultimately leading to a loss of metabolic control.
An electrocardiographic finding in which the R wave of a premature ventricular complex occurs on top of the T wave of the preceding beat. (CDISC)
Problem associated with the device causing unintended therapeutic action to an area of the body other than the intended area.
Escape of radiation (energy in the form of waves or subatomic particles, especially those that cause ionization) through containment structures, leading to unintended exposure.
Problem associated with the degradation of the reception of a wanted signal caused by RF disturbance.
A benign bone neoplasm arising from the remnants of the fetal notochord.
A benign neoplasm of the ovary, originating from granulosa cells.
A hepatotoxin-induced finding in the liver consisting of dilated/cystic bile ducts filled with mucus and cellular debris and surrounded by inflammatory cell infiltrates and often sclerotic connective tissue. Epithelium is pleomorphic and, in cystic glands, may be partially lost resulting in crescent shaped structures. (INHAND)
A benign epithelial neoplasm arising from the pars distalis of the anterior pituitary gland.
A malignant epithelial neoplasm arising from the pars distalis of the anterior pituitary gland.
A benign epithelial neoplasm arising from the pars intermedia of the anterior pituitary gland.
A recombinant therapeutic agent that is identical or similar to an 84-amino-acid polypeptide produced by the parathyroid gland which functions to maintain a constant concentration of calcium ions (Ca2+) in the extracellular fluid. In target tissues, parathyroid hormone (PTH) binds to and activates the PTH receptor (PTHR), a cell surface G protein-coupled receptor; there are two types of receptors, PTHR1 found in bone and the kidney and PTHR2 found primarily in the central nervous system (CNS), pancreas, testis, and placenta. Activation of PTHRs results in the activation of adenylyl cyclase and phospholipase C in target tissue cells, which, depending upon the specific target tissue, results in the enhancement of intestinal Ca2+ absorption, mobilization of bone Ca2+, and renal Ca2+ reabsorption.
A rare, invasive rectal adenocarcinoma characterized by the presence of sheets of malignant epithelial cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. It usually has a favorable prognosis.
An aggressive, high-grade, and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the rectum. It is characterized by the presence of malignant small cells.
Recurrence of symptoms of a disease, at a site different and away from the original site.
Recurrence of symptoms of a disease at the original site.
Problem associated with partial backflow, compromising the device's flow output.
The device appears to elicit undesired response in the patient to the presence of an implanted or invasive device, without inherent device failure, e.g. fibrous encapsulation, or inflammation of the tissue around the device, or extrusion of the device.
Problem associated with the decontamination process not adequately removing unwanted visible soil, foreign material, or organism deposits.
Problem associated with flow rate. Flow volume delivered over time is not reaching intended flow rate.
Problem associated with a nonconforming end result, data, or test results provided by the device to its performance specifications.
Cardiac arrest that is reversed, usually by CPR and/or defibrillation or cardioversion, or cardiac pacing.
Problem associated with an undesired material change in physical property, characterized by rigidity (it resists deformation in response to an applied force).
An adenocarcinoma that arises from the salivary glands. It exhibits ductal differentiation but lacks any of the morphologic features that characterize the other well-defined primary adenocarcinomas of the salivary glands.
A carcinoma that arises from the salivary glands, most often the minor salivary glands. It is characterized by the presence of a monomorphic population of malignant epithelial cells with clear cytoplasm and the absence of morphologic features that define other primary neoplasms of the salivary glands.
A rare, low-grade adenocarcinoma that arises from the salivary glands. It is characterized by the presence of cystic structures lined by ductal cells which are arranged in cribriform patterns. Adjacent ducts show intraductal proliferation.
A rare adenocarcinoma that arises from the salivary glands, most frequently the soft palate and the sublingual gland. It is characterized by the presence of large pools of extracellular mucin in which clusters of malignant epithelial cells are found. Patients usually present with a slow growing mass. It tends to recur locally and metastasize to regional lymph nodes.
A high grade adenocarcinoma that arises from the salivary glands. The vast majority of cases have been described in the parotid gland. It is characterized by the presence of malignant oncocytes. It recurs and metastasizes to regional or distant anatomic sites.
A histopathologic finding characterized by the presence of malignant cells of connective tissue origin in a tumor sample. Examples of connective tissue cells that can undergo malignant transformation include smooth and skeletal muscle cells, adipose tissue cells, osteocytes, and chondrocytes.
Problem associated with an undesirable shallow cut or narrow groove in the surface of the device materials.
Recurrent dental caries involving a discrete area of a tooth including an area adjacent to an existing restoration or sealant.
Problem associated with the unintended activation of the device, or a device having been unexpectedly turned on during use.
Any substance that inhibits serine/threonine protein kinase, an enzyme that phosphorylates the hydroxyl group of serine or threonine on various proteins in various signaling cascades. Inhibition of serine/threonine protein kinase can inhibit cell proliferation and induce apoptosis.
Life-threatening anemia associated with a high risk of infection or bleeding.
An inherited, severe immunodeficiency disorder characterized by abnormalities in the development and function of T cell immunity. The peripheral T lymphocytes are absent or in very low counts. The B lymphocyte counts are normal.
An inherited, severe immunodeficiency disorder characterized by abnormalities in the development and function of T and B cell immunity. The peripheral T and B lymphocytes are absent or in very low counts.
Problem associated with the device inability to act as a barrier for absorption of radiation energy in X-rays, gamma rays, etc.
Insufficient filling of a device. For complete failure to fill use inability to auto-fill. For insufficient filling use short fill. For inconsistent filling - use Volume Accuracy Problem.
An invasive lobular carcinoma characterized by the presence of malignant epithelial cells with large intracytoplasmic lumina that cause displacement of the nuclei towards one pole of the cells.
A melanoma arising in a giant congenital melanocytic nevus. The risk of developing a melanoma in a giant congenital melanocytic nevus has been reported to be between 5% and 50%. The incidence of developing melanoma is higher before the age of 10 and in adult life.
A skin carcinoma displaying cytological characteristics intermediate to nodular basal cell carcinoma and squamous cell carcinoma.
Problem associated with the device moving or sliding from the intended position.
A congenital nevus of small size, with a diameter smaller than 1.5 cm. It presents as a macular, papular or plaque-like lesion.
Indicates a person who is known to have smoked but whose current smoking status is unknown.
The sodium salt of the dextro isomer of lactic acid with alkalinizing and electrolyte replenishing property. Upon metabolism, sodium lactate D is converted to bicarbonate, thereby increasing plasma bicarbonate, which facilitates removal of hydrogen ion and lactate from blood stream and leads to raised blood pH.
Problem associated with undesired damage or breakage in a solder joint of materials used in the device construction.
Indicates that a person has attended college but that they did not receive any degree.
Problem associated with a flash of light related to an electrical discharge into a normally non conductive medium, such as air. Not associated with a discharge between two conductive surfaces.
A morphologic finding indicating the transformation of non-spindle cells to spindle-shaped cells.
The maximum compliance (mobility) of the middle ear system (i.e., the greatest amount of acoustic energy absorbed by the middle ear system (the vertical peak of the tympanogram tracing).
Problem associated with an increase or elongation in a materials' dimension.
A rare, benign sex cord-stromal tumor of the ovary characterized by the presence of a fibrothecomatous stroma and scattered sex cord elements. Although it is usually hormonally inactive, cases associated with endometrial hyperplasia or adenocarcinoma have been reported.
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v6 classification system.
Subglottic cancer with no distant metastasis. (from AJCC 6th Ed.)
Subglottic cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Subglottic cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Subglottic cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Subglottic cancer with metastasis to a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Subglottic cancer with metastasis to a single ipsilateral lymph node, more than 3 cm, but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Subglottic cancer with metastasis in two or more ipsilateral nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Subglottic cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Subglottic cancer with metastasis in a lymph node, more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Subglottic cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Subglottic cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Subglottic cancer in which the tumor is limited to the subglottis. (from AJCC 6th and 7th Eds.)
Subglottic cancer with tumor extending to vocal cord(s) with normal or impaired mobility. (from AJCC 6th and 7th Eds.)
Subglottic cancer with tumor limited to the larynx with vocal cord fixation. (from AJCC 6th and 7th Eds.)
Subglottic cancer with tumor invading cricoid or thyroid cartilage and/or invading tissues behind the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 6th Ed.)
Subglottic cancer with tumor invading prevertebral space, encasing carotid artery, or invading mediastinal structures. (from AJCC 6th Ed.)
Subglottic cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Subglottic cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
Problem associated with suction equipment, which may be a manual, electrical, vacuum or pressure source operated to evacuate and remove undesired substances (air, gas, fluid, or particulates) via tubing and collection bag.
A pathologic finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v6 classification system.
Supraglottic cancer with no distant metastasis. (from AJCC 6th Ed.)
Supraglottic cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Supraglottic cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Supraglottic cancer with no metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with metastasis to a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with metastasis to a single ipsilateral lymph node, more than 3 cm, but not more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with metastasis in two or more ipsilateral nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with metastasis in a lymph node, more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
Supraglottic cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with tumor limited to 1 subsite of supraglottis with normal vocal cord mobility. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with tumor invading the mucosa of more than 1 adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of the tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with tumor limited to larynx with vocal cord fixation and/or invading any of the following: postcricoid area, pre-epiglottic tissues, paraglottic space, and/or minor thyroid cartilage erosion (e.g. inner cortex). (from AJCC 6th Ed.)
Supraglottic cancer with tumor invading through thyroid cartilage and/or invading tissue beyond the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 6th Ed.)
Supraglottic cancer with tumor invading prevertebral space, encasing carotid artery, or invading mediastinal structures. (from AJCC 6th Ed.)
Supraglottic cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Supraglottic cancer with a finding of carcinoma in situ. (from AJCC 6th and 7th Eds.)
A cancer vaccine consisting of E-PRA and E-PSM, two synthetic peptide analogs of PRAME (PReferential Antigen MElanoma) and PSMA (Prostate Specific Membrane Antigen), with potential immunostimulating activity. Upon direct administration into lymph nodes, synthetic peptides E-PRA and E-PSM vaccine may stimulate a cytotoxic T-lymphocyte (CTL) response against PRAME- and PSMA-expressing tumor cells. PRAME and PSMA are tumor-associated antigens upregulated and expressed on the cell surfaces of certain tumor cell types.
Problem associated with packaging damage (tear, rip or hole) prior to the use of the device.
Problem associated with variability of the transmission of telemetry signals.
A testicular seminoma characterized by the presence of uniform round germ cells with glycogen-rich cytoplasm and large nuclei, and a lymphocytic infiltrate.
Problem associated with the failure of the device to deliver the output required for treatment or identification of a disease.
The anhydrous salt form of thioguanine, a synthetic guanosine analogue antimetabolite, with antineoplastic activity. Thioguanine is phosphorylated by hypoxanthine-guanine phosphoribosyltransferase to 6-thioguanylic acid (TGMP) and upon conversion to thioguanosine diphosphate (TGDP) and thioguanosine triphosphate (TGTP), this agent is incorporated into DNA and RNA, resulting in inhibition of DNA and RNA synthesis and cell death. This agent also inhibits glutamine-5-phosphoribosylpyrophosphate amidotransferase, thereby inhibiting purine ribonulceotide synthesis.
A clinical finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v6 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, biopsy or laboratory testing.
A pathologic finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v6 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v6 classification system.
Thyroid cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Thyroid cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Thyroid cancer in which the status of distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Thyroid cancer with no regional lymph node metastasis. (from AJCC 6th and 7th Eds.)
Thyroid cancer with metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Thyroid cancer with metastasis to pretracheal, paratracheal or prelaryngeal/Delphian lymph nodes (Level VI lymph nodes). (from AJCC 6th and 7th Eds.)
Thyroid cancer with metastasis to unilateral, bilateral or contralateral cervical or superior mediastinal lymph nodes. (from AJCC 6th Ed.)
Thyroid cancer in which regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Thyroid cancer with no evidence of primary tumor. (from AJCC 6th and 7th Eds.).
Thyroid cancer with a tumor size of 2 cm or less in greatest dimension, and limited to the thyroid gland. (from AJCC 6th and 7th Eds.)
Thyroid cancer with a tumor size greater than 2 cm but not more than 4 cm in greatest dimension, and limited to the thyroid gland. (from AJCC 6th and 7th Eds.)
Thyroid cancer with a tumor size greater than 4 cm in greatest dimension and limited to the thyroid gland, or a tumor of any size with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues). (from AJCC 6th and 7th Eds.)
Thyroid cancer with any size tumor extending beyond the thyroid gland capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, recurrent laryngeal nerve, prevertebral fascia, or encasing the carotid artery or mediastinal vessels. All anaplastic carcinomas are also classified as pT4, with separate subclassification. (from AJCC 6th Ed.)
Anaplastic carcinoma confined to the thyroid gland, which is surgically resectable. (AJCC 6th Ed.)
Thyroid cancer with any size tumor extending beyond the thyroid gland capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus or recurrent laryngeal nerve. (from AJCC 6th Ed.)
Anaplastic carcinoma extending beyond the capsule of the thyroid gland, which is surgically unresectable. (from AJCC 6th Ed.)
Thyroid cancer with any size tumor invading the prevertebral fascia, or encasing the carotid artery or mediastinal vessels.
Thyroid cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
A follicular carcinoma of the thyroid gland which shows limited capsular and/or vascular invasion.
A disodium salt form of tipranavir, a non-peptidomimetic agent that inhibits both wild type and drug resistant forms of human immunodeficiency virus (HIV) protease.
A highly lipophilic preparation of 7-Ethyl-10-hydroxycamptothecin (SN-38) with potential antineoplastic activity. SN2310 is an oil-in-water emulsion of tocopherol covalently linked, via a succinate linker, to SN-38, a synthetic derivative of the cytotoxic alkaloid camptothecin. After succinate linker is hydrolyzed in vivo, the active moiety SN-38 is released and selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-stranded DNA breaks and inducing lethal double-stranded DNA breaks. This inhibits DNA replication and triggers programmed cell death. SN2310 emulsion provides longer circulation time and potentiates drug exposure as compared to the unconjugated SN-38.
An aggressive adenocarcinoma that arises from the sweat glands. It usually presents as a firm, erythematous nodular lesion in the axilla. Morphologically, it is characterized by the presence of tubular structures and apocrine differentiation.
A Sertoli cell tumor that arises from the ovary and is characterized by the presence of cells that are distended by the presence of intracytoplasmic lipid.
The process whereby normal tissue cells and structures are replaced by tumor cells.
Problem associated with the transfer of fluid between the blood and dialysate through the dialysis membrane due to a pressure gradient (trans-membrane pressure) existing between the blood and dialysate compartments.
The device does not provide or display a valid reading.
Problem associated with an insufficient dose of therapeutic agents, e.g., drugs or fluids being delivered into a patient under positive pressure.
Problem related to failure of the device to properly detect intrinsic cardiac activity and respond appropriately.
A usually aggressive malignant epithelial neoplasm composed of atypical cells which do not display evidence of glandular or squamous differentiation and giant cells resembling osteoclasts.
Problem associated with the device impacting with another object.
Problem associated with the device turning on when not intended.
Problem associated with unexpected discharge of the device from expected location includes but not limited to the device such as clip appliers, film cartridge, staples.
Movement of the device to an unintended location within the body.
Problem associated with any motion of the system or components that was not initiated by the user.
Indicates that a person's smoking status is unknown.
Problem due to the device's undesired unravelling of material (e.g. disentangled, unwound etc.).
Problem associated with the device's loss of packaging seal.
Problem associated with the mechanical stability of a device.
An uncommon malignant neoplasm arising from the uterine corpus. It is characterized by the presence of a malignant epithelial component and a benign mesenchymal (usually fibrous) component.
A malignant neoplasm arising from the uterine corpus. This category includes endometrial carcinoma and carcinosarcoma.
A clinical finding about one or more characteristics of uterine corpus cancer, following the rules of the TNM AJCC v6 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, biopsy and laboratory testing.
A pathologic finding about one or more characteristics of uterine corpus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of uterine corpus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of uterine corpus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes. TNM pathologic regional lymph nodes findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of uterine corpus cancer, following the rules of the TNM AJCC v6 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
Uterine corpus cancer in which there is no evidence of distant metastasis. (from AJCC 6th Ed.)
Uterine corpus cancer with distant metastasis, including intra-abdominal lymph nodes other than para-aortic or inguinal lymph nodes, excluding metastasis to the vagina, pelvic serosa, or adnexa. (from AJCC 6th Ed.)
Uterine corpus cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Uterine corpus cancer in which there is no evidence of regional lymph node metastasis. (from AJCC 6th Ed.)
Uterine corpus cancer with metastasis to the pelvic or para-aortic lymph nodes. (from AJCC 6th Ed.)
Uterine corpus cancer in which regional lymph nodes cannot be assessed. (from AJCC 6th Ed.)
Uterine corpus cancer in which there is no evidence of a primary tumor. (from AJCC 6th Ed.)
Uterine corpus cancer with tumor confined to the corpus uteri. (from AJCC 6th Ed.)
Uterine corpus cancer with tumor limited to the endometrium. (from AJCC 6th Ed.)
Uterine corpus cancer with tumor invasion of less than one-half of the myometrium. (from AJCC 6th Ed.)
Uterine corpus cancer with tumor invasion of one-half or more of the myometrium. (from AJCC 6th Ed.)
Uterine corpus cancer with invasion of the cervix without extension beyond the uterus. (from AJCC 6th Ed.)
Uterine corpus cancer limited to the glandular epithelium of the endocervix. (from AJCC 6th Ed.)
Uterine corpus cancer with invasion of the cervical stroma. (from AJCC 6th Ed.)
Uterine corpus cancer with local or regional involvement as defined in pT3a or pT3b. (from AJCC 6th Ed.)
Uterine corpus cancer with tumor involvement of the serosa or adnexa (either from direct extension or from metastasis), or with the presence of cancer cells in either ascites or peritoneal washings. (from AJCC 6th Ed.)
Uterine corpus cancer with tumor involvement of the vagina either from direct extension or metastasis. (from AJCC 6th Ed.)
Uterine corpus cancer with tumor invasion of the bladder mucosa or bowel mucosa. Bullous edema is not sufficient to classify a tumor as T4. (from AJCC 6th Ed.)
Uterine corpus cancer in which primary tumor cannot be assessed. (from AJCC 6th Ed.)
Uterine corpus cancer in situ. (from AJCC 6th Ed.)
A benign microacinar proliferation occurring exclusively in the area of the utricle.
Narrowing of the opening of one or more of the four valves of the heart.
Problem associated with the circulation of fresh air in the immediate atmosphere in which the device is being used.
A benign microacinar proliferation occurring exclusively in the verumontanum and adjacent posterior urethra where the ejaculatory ducts and utricle empty into the urethra. Crystalloids and intraluminal mucin are usually absent, but; intraluminal corpora amylacea are often present. The lining epithelium typically consists of bland cuboidal to columnar luminal cells with underlying basal cells.
Problem associated with the undesirable mechanical oscillation in a device.
An emulsion containing the tartrate salt of the semisynthetic vinca alkaloid vinorelbine with antineoplastic activity. Vinorelbine binds to tubulin, inhibiting tubulin polymerization into microtubules; cell division is prevented, the cell cycle is arrested metaphase and cell death ensues. In this formulation vinorelbine is emulsified in a homogeneous suspension of nanoparticles, which protects the venous endothelium from coming into direct contact with the active ingredient, potentially reducing vinorelbine-associated venous toxicity at the venous injection site.
Inconsistent filling of a device. This describes a problem which is observed to vary between overfilling and under filling, and may be intermittent. Use Overfill or Short Fill if problem is consistent.
A morphologic architectural pattern in which the tumor cells spread in a wedge-shaped pattern.
A biologically active, cystine-rich, whey-based protein isolate. Whey protein isolate is broken down in the body into cystine and glutamylcystine, which travel safely in the blood stream, upon cell entry, deliver a sustained amount of free cysteine to the cells. The available cysteine allows cells to synthesize glutathione (GSH), a tripeptide containing amino acids glycine, glutamate and cysteine, thereby maintaining and increasing intracellular GSH concentrations. GSH plays a major role as an antioxidant, thereby protecting cells from oxidative damage due to harmful substances such as free radicals and reactive oxygen compounds.
A diphenyl ketoaldehyde derivative with broad-spectrum antiviral activity.
The arginine salt of zofenoprilat, a sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Zofenoprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Zofenoprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A nonpeptide angiotensin II receptor antagonist with antihypertensive activity. Zolasartan selectively competes with angiotensin II for the binding of the angiotensin II (AT1) receptor subtype 1 in vascular smooth muscle, thereby blocking angiotensin II-mediated vasoconstriction resulting in vascular dilatation. In addition, the antagonistic effect on AT1 in the adrenal gland, prevents angiotensin II-induced stimulation of aldosterone synthesis and secretion by the adrenal cortex. This blocks the effects of aldosterone leading to an increase in sodium excretion and water and eventually a reduction in plasma volume and blood pressure.
The disodium salt form of zoledronate, a synthetic imidazole, third generation bisphosphonate analog of pyrophosphate with antiresorptive activity. Zoledronate binds to hydroxyapatite crystals in the bone matrix and inhibits farnesyl pyrophosphate (diphosphate) synthase, thereby preventing protein prenylation within the mevalonate pathway. This leads to the loss of downstream metabolites essential for osteoclast function, leading to the induction of apoptosis and eventually, osteoclast-cell death. By preventing osteoclast-mediated bone resorption, zoledronate decreases bone turnover and stabilizes the bone matrix.
Indicates that 10th grade is the highest level of educational achievement.
Indicates that 11th grade is the highest level of educational achievement.
Indicates that a person was in school through 12th grade but they did not receive a high school diploma.
Indicates that 1st grade is the highest level of educational achievement.
Indicates that 2nd grade is the highest level of educational achievement.
Indicates that 3rd grade is the highest level of educational achievement.
Indicates that 4th grade is the highest level of educational achievement.
Indicates that 5th grade is the highest level of educational achievement.
Indicates that 6th grade is the highest level of educational achievement.
Indicates that 7th grade is the highest level of educational achievement.
Indicates that 8th grade is the highest level of educational achievement.
Indicates that 9th grade is the highest level of educational achievement.
Any natural or synthetic substance that enhances the activity of any phase II metabolic enzymes. Phase II detoxification enzymes, such as glutathione-S-transferase (GST), glucuronyl transferase, acyl transferase, or sulfotransferase, catalyze conjugation reactions of xenobiotics or metabolites formed in phase I reactions. Conjugation reactions greatly enhance polarity of xenobiotics or their metabolites, thereby facilitate their elimination from the body. Phase II conjugation reactions include glucuronidation, methylation, acetylation, and glutathione, sulfate and amino acid conjugation.
Bone marrow failure defined as pancytopenia, secondary to hepatitis.
A morphologic finding that indicates the presence of cells with abundant eosinophilic and granular cytoplasm in a tumor sample.
A pathologic finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes. TNM pathologic regional lymph nodes findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A morphologic finding indicating the presence of an architectural pattern of tubular formations in a tissue sample.
A benign or malignant lesion typically arising in the period between infancy and adulthood.
A clinical finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v6 classification system.
An adenoma that arises from the parotid gland. It is characterized by an oncocytic, often papillary, epithelial component, dense lymphoid stroma, and cystic spaces. A strong association with smoking has been reported. It typically presents as a painless swelling in the lower portion of the parotid gland.
A disorder characterized by unusually late sexual maturity.
Stage 0a includes: Ta, N0, M0. Ta: Papillary noninvasive carcinoma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
A pathologic process in which alterations at the molecular level result in a more aggressive cytologic and phenotypic profile and clinical course of a malignant neoplasm.
A rare benign neoplasm of the endocardium. The vast majority of cases arise in the heart valves. Histopathologic examination reveals a papilloma lined by endothelial cells with a central avascular core which contains fibroblasts and elastic fibers. Patients may be asymptomatic or present with ischemic or embolic events.
A tumor with myoepithelial differentiation that lacks an infiltrative growth pattern and does not metastasize.
A carcinoma that has spread to the skin from its original site of gowth.
Any of the synthetic agents that bind to and antagonize growth hormone receptors, resulting in inhibition of somatotrophic actions triggered by growth hormone stimulated receptor signal transduction.
A synthetic quinoline derivative with multidrug resistance (MDR) modulating properties. Dofequidar fumarate, like many other MDR reversal agents, binds competitively to the drug-binding site of the transmembrane P-glycoprotein efflux pump (P-gp). Once bound to the P-gp efflux pump, dofequidar is transported out of transformed cells by a mechanism similar to that used by cytotoxic drugs, thereby blocking the efflux of these compounds from the cell. Inhibition of the efflux pump by this agent leads to a retention of the cytotoxic drug resulting in increased intracellular drug concentrations, thereby enhancing cytotoxicity. Dofequidar has demonstrated reversal of the MDR phenotype in those cells exposed to various chemotherapeutic agents, such as vinca alkaloids and anthracyclines.
A nonsteroidal 2-phenyl indole and a selective estrogen receptor modulator (SERM) with potential antineoplastic activity. Pipendoxifene antagonizes binding of estradiol to estrogen receptor alpha (ER alpha), thereby inhibiting ER alpha-mediated gene expression, interfering with estrogen activity and inhibiting estrogen-stimulated growth in estrogen-dependent breast cancer. In addition, this agent also exerts intrinsic estrogenic activity depending on the tissue types.
A novel hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase.
An orally bioavailable, small molecule, non-polyglutamatable, antifolate quinazoline derivative thymidine synthetase inhibitor with potential antineoplastic activity. Plevitrexed is transported into the cell via the physiological reduced folate carrier (RFC) system. Intracellularly, this agent selectively binds to the folate binding site of thymidylate synthase and inhibits thymidine synthesis, which may result in DNA synthesis inhibition and apoptosis.
The alaninate salt of a vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with potential antineoplastic activity. Brivanib strongly binds to and inhibits VEGFR2, a tyrosine kinase receptor expressed almost exclusively on vascular endothelial cells; inhibition of VEGFR2 may result in inhibition of tumor angiogenesis, inhibition of tumor cell growth, and tumor regression.
Vitamin K-dependent protein C (461 aa, ~52 kDa) is encoded by the human PROC gene. This protein is involved in the degradation of factors Va and VIIIa.
The hydrochloride salt form of hexaminolevulinate, a hexyl ester of the heme precursor 5-aminolevulinic acid (ALA) with potential photosensitizing activity. Hexaminolevulinate serves as a precursor of photoactive porphyrins (PAPs), particularly protoporphyrin IX (PpIX), which selectively accumulate in rapidly proliferating cells, such as those seen in tumor tissue. When exposed to blue light, PAPs are activated and emit red light thereby allowing tumor imaging.
A soluble, complex bismuth salt of citric acid used in combination with metronidazole and tetracycline to treat stomach ulcers caused by Helicobacter pylori infections.
A bicyclam with hematopoietic stem cell-mobilizing activity. Plerixafor blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell (HSC) release from bone marrow and HSC movement into the peripheral circulation.
Prolonged complete obstruction of the coronary artery. (ACC)
A T-cell peripheral neoplasm characterized by a persistent (>6 months) increase in the number of peripheral blood large granular lymphocytes, without a clearly identified cause. (WHO, 2001)
The omission of atrial activation that is caused by transient cessation of impulse generation at the SINOATRIAL NODE. It is characterized by a prolonged pause without P wave in an ELECTROCARDIOGRAM. Sinus arrest has been associated with sleep apnea (REM SLEEP-RELATED SINUS ARREST).
A group of neural cortical developmental malformations of diverse genetic causes. Clinical manifestations include epilepsy and developmental delays.
Disorders comprising a spectrum of brain malformations representing the paradigm of a diffuse neuronal migration disorder. They result in cognitive impairment; SEIZURES; and HYPOTONIA or spasticity. Mutations of two genes, LIS1, the gene for the non-catalytic subunit of PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE IB; and DCX or XLIS, the gene for doublecortin, have been identified as the most common causes of disorders in this spectrum. Additional variants of classical (Type I) lissencephaly have been linked to RELN, the gene for reelin, and ARX, the gene for aristaless related homeobox protein. (From Leventer, R.J., et al, Mol Med Today. 2000 Jul;6(7):277-84 and Barkovich, A.J., et al, Neurology. 2005 Dec 27;65(12):1873-87.)
Phenomena and pharmaceutics of compounds that selectively bind to a specific receptor and trigger a response. They mimic the action of endogenous biochemical molecules. Their effect can be countered by antagonists (DRUG ANTAGONISM).
Phenomena and pharmaceutics of compounds that bind to the same receptor binding-site as an agonist (DRUG AGONISM) for that receptor but exerts the opposite pharmacological effect.
Measurable biological parameters that serve for drug development, safety and dosing (DRUG MONITORING).
Drug agonism involving selective binding but reduced effect. This can result in some degree of DRUG ANTAGONISM.
A family of naturally occurring polyketides that consist of C32 or C34 long chain fatty acids and combined with a propan-2-ol unit at C-2 to form a gamma-lactone, which are isolated from various species of the plant family Annonaceae, with potential antineoplastic and antimicrobial activity. Annonaceous acetogenins bind to the ubiquinone catalytic site(s) within the mitochondrial NADH:ubiquinone oxidoreductase (complex I), and block the electron transport chain in mitochondria. In addition, the acetogenins bind to and block the activity of ubiquinone-linked NADH oxidase, an enzyme overexpressed in the plasma membranes of cancer cells. This inhibits adenosine triphosphate (ATP) production, decreases intracellular ATP levels, and induces tumor cell apoptosis. Compared to normal cells, cancer cells have higher ATP demands. The Annonaceous acetogenins also inhibit microbial glucose dehydrogenase 6.
An extranodal neoplasm, usually possessing an NK-cell phenotype and associated with EPSTEIN-BARR VIRUS. These lymphomas exhibit a broad morphologic spectrum, frequent necrosis, angioinvasion, and most commonly present in the midfacial region, but also in other extranodal sites.
Vaccines or candidate vaccines used to prevent or treat PSEUDOMONAS INFECTIONS.
A heterogeneous group disorders characterised by short, brittle hair with low-sulphur content (due to an abnormal synthesis of the sulphur containing keratins). The abnormalities are usually obvious at birth, with variable clinical expression. Trichothiodystrophy is an autosomal recessive disorder. In the photosensitive group 95% have mutations within the XPD (ERCC2) gene (localised to 19q13.2-q13.3). The remaining cases are caused by mutations within the XPB gene. So far, no gene has been isolated for the nonphotosensitive group. The variants of Trichothiodystrophy depending on their different associations are: BIDS syndrome, IBIDS syndrome, PIBIDS syndrome, Sabinas syndrome, SIBIDS syndrome, Itin syndrome and Pollitt syndrome.
Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.
A bony projection that forms on the joints of the body.
A component of Jacobsen Syndrome linked to FLI1 gene at 11q23.
Compounds that interfere with FATTY ACID SYNTHASE resulting in a reduction of FATTY ACIDS. This is a target mechanism in humans of some ANTINEOPLASTIC AGENTS and ANTI-OBESITY AGENTS and of some ANTI-INFECTIVE AGENTS which interfere with CELL WALL and CELL MEMBRANE formation.
Wolf-Hirschhorn syndrome is a congenital malformation syndrome characterized by pre- and postnatal growth deficiency, developmental disability of variable degree, characteristic craniofacial features ('Greek warrior helmet' appearance of the nose, high forehead, prominent glabella, hypertelorism, high-arched eyebrows, protruding eyes, epicanthal folds, short philtrum, distinct mouth with downturned corners, and micrognathia), and a seizure disorder (Battaglia et al., 2008).
A follicular lymphoma which contains up to 5 centroblasts per 40X high-power microscopic field.
Presence of a hole or holes in the ventricular septum.
The diammonium salt of glycyrrhizin and the active constituent in the traditional Chinese medicinal herb Glycyrrhiza uralensis (Chinese liquorice or Gan-Cao) with anti-inflammatory, antioxidant and hepatoprotective properties. Diammonium glycyrrhizinate (DG) is slowly metabolized within the cells into glycyrrhetic acid, which inhibits enzymes that control cortisol metabolism and contributes to this agent's anti-inflammatory effect. Although the exact mechanism of action remains to be fully elucidated, DG may prevent or reduce hepatotoxicity via the scavenging of free radicals. This agent also upregulates the expression of transcription coactivator PGC-1alpha and modulates hepatic enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase and glutathion peroxidase.
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis) or just below the pulmonary valve (infundibular stenosis).
A congenital malformation of veins which drain normal brain characterized by a caput medusae or an umbrellalike convergence of multiple venules on a single, or occasionally multiple, enlarged parenchymal or medullary vein, like the trunk of a tree or the shank of an umbrella. This dilated terminal vein penetrates the cortex to drain either (a) superficially to cortical veins or sinuses, (b) deeply to subependymal veins of the lateral ventricle and then into the galenic system, (c) to the fourth ventricle and then to the pontomesencephalic vein, or (d) to the precentral cerebellar vein and into the galenic system.
A synthetic small molecule with antimitotic and potential antineoplastic activities. Indibulin binds to a site on tubulin that is different from taxane- or Vinca alkaloid-binding sites, destabilizing tubulin polymerization and inducing tumor cell cycle arrest and apoptosis. This agent has been shown to be active against multidrug-resistant (MDR) and taxane- resistant tumor cell lines.
Narrowing of the coronary arteries due to fatty deposits inside the arterial walls. The diagnostic criteria may include documented history of any of the following: documented coronary artery stenosis greater than or equal to 50% (by cardiac catheterization or other modality of direct imaging of the coronary arteries); previous coronary artery bypass surgery (CABG); previous percutaneous coronary intervention (PCI); previous myocardial infarction. (ACC)
A small molecule and MDM2 (murine double minute 2) inhibitor, with potential antineoplastic activity. In cancer cells, nutlin-3a antagonizes the binding of MDM2 to p53, thereby preventing MDM2-mediated p53 degradation. This results in stabilizing and activating p53-dependent cell cycle arrest and apoptosis. The protein MDM2, a negative regulator of p53 activity, is overexpressed in many cancer cell types; the tumor suppressor p53 is mutated or deleted in about 50% of all cancers but active in the other 50%.
An orally-available triazole antifungal drug for the treatment of acute skin and mucosal fungal infections. Pramiconazole has a very long half-life allowing for once a week dosing but may display erratic absorption and idiosyncratic liver toxicity similar to intraconazole and fluconazole.
An autoimmune, systemic, giant cell granulomatous arteritis predominantly involving the arteries that supply blood to the central nervous system, head and eyes. Superficial arteries of the scalp that are involved tend to be enlarged and tender. Signs and symptoms include headaches, myalgias, visual disturbances, and skin necrosis.
Active enantiomers and selective derivatives of second generation H1 antagonists.
A subtype with ventricular septal defect clearly away from the semilunar valves of the AORTA and the PULMONARY ARTERY.
A subtype with pulmonary ventricular septal defect.
Sudden onset of shortness of breath that causes one to awaken coughing or wheezing; it may be associated with congestive heart failure or chronic obstructive pulmonary disease.
An abnormal twisting or rotation of a bodily part or member on its axis.
A quinoline-3-carboxamide linomide analogue with antiangiogenic and potential antineoplastic activities. Tasquinimod has been shown to decrease blood vessel density but the exact mechanism of action is not known. This agent has also been shown to augment the antineoplastic effects of docetaxel and androgen ablation in a murine model of prostate cancer involving human prostate cancer xenografts.
A prostaglandin D2 receptor (DP1) antagonist with niacin-induced vasodilation inhibiting activity. Laropiprant binds to and inhibits the activity of DP1, a G-protein coupled receptor. Via competing with prostaglandin D2 (PG D2) for binding to DP1, this agent prevents PG D2-induced vasodilation and increased blood flow. As niacin induces the synthesis of PG D2, predominantly in the skin, administration of laropiprant may prevent niacin-induced vasodilation in the skin and facial flushing.
An orally bioavailable inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity. Upon oral administration, WP1066 specifically binds to both JAK2 and its mutated form JAK2 V617F, and inhibits their phosphorylation and activation. In addition, this agent degrades JAK2 protein. This results in the inhibition of the JAK- signal transducer and activator of transcription (STAT) and phosphoinositide-3-kinase (PI3K)/AKT signaling pathways, resulting in the induction of apoptosis in tumor cells overexpressing JAK2. JAK2, a tyrosine kinase, is overexpressed in a variety of tumor cells and is correlated with increased tumor cell proliferation and survival. The mutated form JAK2 V617F has a valine-to-phenylalanine modification at position 617 and plays a key role in tumor cell proliferation and survival.
A human IgG1k monoclonal antibody against the CD4 receptor on T-lymphocytes, with potential antineoplastic and immunosuppressing activities. Zanolimumab targets and binds to the CD4 receptor on certain T-cells thereby preventing the interaction between the CD4 receptor and the major histocompatibility complex class II molecule. This prevents activation of CD4 positive T cells. In addition, zanolimumab is able to induce an antibody-dependent cellular cytotoxicity (ADCC) response against CD4-expressing tumor cells. CD4, a receptor located on a subset of T-lymphocytes, is upregulated in T-cell lymphomas.
A selective, orally bioavailable, pyrimidinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. In addition to its effect on glucose levels, alogliptin may inhibit inflammatory responses by preventing the toll-like receptor 4 (TLR-4)-mediated formation of proinflammatory cytokines.
A poly(ADP-ribose) polymerase (PARP) -1 and -2 inhibitor with chemosensitizing and antitumor activities. With no antiproliferative effects as a single agent at therapeutic concentrations, ABT-888 inhibits PARPs, thereby inhibiting DNA repair and potentiating the cytotoxicity of DNA-damaging agents. PARP nuclear enzymes are activated by DNA single or double strand breaks, resulting in the poly(ADP-ribosyl)ation of other nuclear DNA binding proteins involved in DNA repair; poly(ADP-ribosyl)ation contributes to efficient DNA repair and to survival of proliferating cells exposed to mild genotoxic stresses as induced by as oxidants, alkylating agents or ionizing radiation.
A peptide-based cancer vaccine consisting of two human leukocyte antigen (HLA)-A*0201 restricted 9-mer epitopes derived from the human telomerase reverse transcriptase (hTERT), TERT 572Y (YLFFYRKSV; TYR-Vx001) and TERT 572 (RLFFYRKSV; ARG-Vx001), with potential immunostimulating and antineoplastic activities. Subcutaneous injection of TERT(572Y) peptide followed by subcutaneous administration of the TERT(572) peptide may elicit a specific and possibly optimal cytotoxic T cell (CTL) response against hTERT-expressing tumor cells. hTERT, the catalytic subunit of human telomerase, is an human leukocyte antigen-A*0201-restricted cryptic epitope of telomerase. TERT is expressed in the majority of human cancer cells, is not expressed or is expressed at very low levels in normal cells and plays a key role in tumorigenesis. TERT572Y is the optimized variant of the native cryptic peptide TERT572 in which tyrosine has been substituted for an arginine at position 1; TERT572Y shows increased HLA-A*0201 binding affinity compared to TERT572.
The magnesium salt form of the saponin, isoglycyrrhizinate, a derivative of glycyrrhizic acid extracted from the roots of the plant Glycyrrhiza glabra, with potential anti-inflammatory, antioxidant and hepatoprotective activities. Although the exact mechanism of action remains to be fully elucidated, magnesium isoglycyrrhizinate may prevent or reduce hepatotoxicity through the scavenging of free radicals. This agent also modulates the activity of hepatic enzymes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD) and glutathione peroxidase.
A potent and reversible inhibitor of the gastric H+/K+ ATPase proton pump with potassium-competitive acid blocking (P-CAB) activity. Soraprazan binds very specifically, competitively and reversibly to the potassium binding site of the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting the pump's activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production.
A cancer vaccine comprised of a recombinant modified vaccinia Ankara (MVA) viral vector encoding the wild-type form of the tumor protein p53 (wt p53), with potential immunostimulating and antineoplastic activities. Upon subcutaneous vaccination with MVA vaccine expressing p53, the expressed p53 may stimulate the host immune system to mount a p53-specific cytotoxic T-lymphocyte (CTL) response against tumor cells expressing p53, resulting in tumor cell lysis. The MVA viral vector, derived from the replication-competent strain Ankara, is a highly attentuated, replication-defective vaccinia strain and is incapable of virion assembly. The p53 gene, a tumor suppressor gene, is mutated in many cancer cell types.
An agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic activity.
Heart failure caused by dysfunction of the MYOCARDIUM, leading to defective cardiac emptying (contraction) or filling (relaxation).
A vascular anomaly due to proliferation of blood or lymphatic vessels that forms a tumor-like mass. Vessels in the angioma may or may not be dilated.
A tumor-like mass with large vascular space that is filled with blood or lymph.
An eating away or breakdown of any type of external or internal human tissue including but not limited to skin, teeth, mucosa, or somatic, which involves only the outer tissue layer. When tissue surrounds an implanted device, the tissue breakdown may result in migration and loss of the implant material and may result in further complications such as infection or abscess.
Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety.
An abnormal reduction in dihydropyrimidine dehydrogenase (NADP+) activity.
Mevalonic aciduria, the first recognized defect in the biosynthesis of cholesterol and isoprenoids, is a consequence of a deficiency of mevalonate kinase (ATP:mevalonate 5-phosphotransferase; EC 2.7.1.36). Mevalonic acid accumulates because of failure of conversion to 5-phosphomevalonic acid, which is catalyzed by mevalonate kinase. Mevalonic acid is synthesized from 3-hydroxy-3-methylglutaryl-CoA, a reaction catalyzed by HMG-CoA reductase (142910). Mevalonic aciduria is characterized by dysmorphology, psychomotor retardation, progressive cerebellar ataxia, and recurrent febrile crises, usually manifesting in early infancy, accompanied by hepatosplenomegaly, lymphadenopathy, arthralgia, and skin rash. The febrile crises are similar to those observed in hyperimmunoglobulinemia D and to periodic fever syndrome (HIDS; 260920), which is also caused by mutation in the MVK gene (summary by Prietsch et al., 2003).
A clonal proliferation of immunoglobulin-secreting plasma cells. This category includes plasma cell myeloma, plasma cell leukemia, plasmacytoma, monoclonal immunoglobulin deposition disease, and monoclonal gammopathy of undetermined significance.
A fetal heart rate acceleration that lasts 2 to less than 10 minutes.
Fetal heart rate variability not detected during intrapartum fetal heart monitoring.
A disorder characterized by clinically significant sexual dysfunction (including impaired desire, impaired arousal, impaired orgasm, or sexual pain) that is fully explained by substance use.
Haemophilus influenzae type b conjugate and Hepatitis B vaccine.
A biologic subset of breast carcinoma defined by high expression of HER2, GRB7, and TRAP100, and by lack of expression of estrogen receptor (ER).
An indication that the results from radiographic and pathological testing correlate.
An indication that the results from radiographic and pathological testing do not correlate.
A qualifier used to describe the agreement between radiographic and pathologic findings.
Hereditary angioedema without abnormal C1 inhibitor levels or function. Found mostly in females in which symptoms may be triggered by pregnancy or estrogen-containing oral contraceptives. A few cases have been associated with gain of function mutations of coagulation factor XII
Aromatase deficiency is a rare autosomal recessive disorder in which individuals cannot synthesize endogenous estrogens. If a fetus lacks aromatase activity, dehydroepiandrosterone sulfate produced by the fetal adrenal glands cannot be converted to estrogen by the placenta, and is converted to testosterone peripherally and results in virilization of both fetus and mother. Virilization manifests as pseudohermaphroditism in female infants, with hirsutism and acne in the mother; the maternal indicators resolve following delivery. Affected females are usually diagnosed at birth because of the pseudohermaphroditism. Cystic ovaries and delayed bone maturation can occur during childhood and adolescence in these girls, who present at puberty with primary amenorrhea, failure of breast development, virilization, and hypergonadotropic hypogonadism. Affected males do not present with obvious defects at birth. Their clinical symptoms include tall stature, delayed skeletal maturation, delayed epiphyseal closure, bone pain, eunuchoid body proportions, and excess adiposity. Estrogen replacement therapy reverses the symptoms in males and females (summary by Jones et al., 2007).
An autosomal recessive condition that results in aromatase deficiency in the placenta, causing temporary virilization of the pregnant woman and virilization of her 46,XX fetus.
A myxoma (tumor of primitive connective tissue) of the heart. Cardiac myxomas consist of stellate to plump, cytologically bland mesenchymal cells set in a myxoid stroma. Cardiac myxomas are of endocardial origina and general project from the endocardium into a cardiac chamber.
A disorder that occurs after the death of a significant other, in which the experience of distress accompanying bereavement fails to follow normative expectations and manifests in functional impairment.
Impaired ability to modify lifestyle and/or actions in a manner that improves the level of wellness.
An intermittent esotropia with binocular single vision present at distance fixation but esotropia on accommodation for near fixation. Usually associated with hypermetropia but patients can be emmetropic and rarely myopic. Associated with a high accommodative convergence/accommodation (AC/A) ratio. [ORCID:0000-0003-0986-4123]
Episodes of migraine occurring on 15 or more days per month, for more than three months.
The hydrochloride salt form of vardenafil, a benzenesulfonamide derivative and phosphodiesterase type 5 (PDE5) inhibitor with vasodilatory activity. Vardenafil selectively inhibits PDE5, thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa and corpus spongiosum of the penis. The inhibition of cGMP degradation results in prolonged muscle relaxation, vasodilation, and blood engorgement of the corpus cavernosa, thereby prolonging penile erection.
An injectable formulation of albumin-bound paclitaxel NANOPARTICLES.
A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.
A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.
A congenital abnormality of the arteries and veins, lymph vessels or veins and lymph vessels.
A disorder characterized by sudden, often repetitive, spasmodic contraction of the thoracic cavity, resulting in violent release of air from the lungs and usually accompanied by a distinctive sound.
A pharmaceutical preparation of amlodipine and valsartan that is used for the treatment of HYPERTENSION.
A disorder characterized by the collapse of part or the entire lung.
A disorder characterized by inflammation of the lip.
A disorder characterized by a discharge of excessive gas from the lower GI tract.
A disorder characterized by a localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel.
An adverse reaction characterized by darkening of the skin.
A disorder characterized by a necrotic process occurring in the soft tissues of the pelvis.
A disorder characterized by bleeding from the rectal wall and discharged from the anus.
A disorder characterized by weight gain, dyspnea, pleural and pericardial effusions, leukocytosis and/or renal failure originally described in patients treated with all-trans retinoic acid.
A disorder characterized by milky pleural effusion (abnormal collection of fluid) resulting from accumulation of lymph fluid in the pleural cavity.
Unintended facial pain associated with a medical procedure or administration of a drug.
Uncontrolled contractions of muscles fibers in the left ventricle not producing contraction of the left ventricle. Ventricular fibrillation usually begins with a ventricular premature contraction and a short run of rapid ventricular tachycardia degenerating into uncoordinating ventricular fibrillations.
A finding of impaired integrity to the anatomic site of an adverse thermal reaction. Burns can be caused by exposure to chemicals, direct heat, electricity, flames and radiation. The extent of damage depends on the length and intensity of exposure and time until provision of treatment.
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
A disorder characterized by an abnormal communication between the duodenum and another organ or anatomic site.
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
A disorder characterized by the adrenal cortex not producing enough of the hormone cortisol and in some cases, the hormone aldosterone. It may be due to a disorder of the adrenal cortex as in Addison's disease or primary adrenal insufficiency.
A disorder characterized by a loss of appetite.
A disorder characterized by cessation of breathing.
A disorder characterized by a dysrhythmia without discernible P waves and an irregular ventricular response due to multiple reentry circuits. The rhythm disturbance originates above the ventricles.
A disorder characterized by a dysrhythmia with organized rhythmic atrial contractions with a rate of 200-300 beats per minute. The rhythm disturbance originates in the atria.
A disorder characterized by an inability of the ventricles to fill with blood because the myocardium (heart muscle) stiffens and loses its flexibility.
The presence of inflammatory changes in the gallbladder.
A disorder characterized by inflammation of the colon.
A disorder characterized by irregular and infrequent or difficult evacuation of the bowels.
A disorder characterized by excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
A disorder characterized by an increase in frequency and/or loose or watery bowel movements.
A disorder characterized by systemic pathological activation of blood clotting mechanisms which results in clot formation throughout the body. There is an increase in the risk of hemorrhage as the body is depleted of platelets and coagulation factors.
A disorder characterized by flaky and dull skin; the pores are generally fine, the texture is a papery thin texture.
A multifunctional antiangiogenic agent derived from shark cartilage with potential antineoplastic activity. Shark cartilage extract AE-941 competitively inhibits the binding of pro-angiogenic vascular endothelial growth factor (VEGF) to its cellular receptor, thereby inhibiting endothelial cell proliferation. This agent also inhibits matrix metalloproteinases (MMPs), stimulates tissue plasminogen activator (tPA), and activates caspase-mediated apoptotic pathways in endothelial cells.
A disorder characterized by an uncomfortable sensation of difficulty breathing.
A disorder characterized by an abnormal communication between the esophagus and another organ or anatomic site.
A disorder characterized by inflammation of the esophageal wall.
A disorder characterized by an abnormal communication between the gallbladder and another organ or anatomic site.
A finding of traumatic injury to the bone in which the continuity of the bone is broken.
A disorder characterized by a necrotic process occurring in the soft tissues of the head.
A disorder characterized by bleeding from the ovary.
A disorder characterized by bleeding from the kidney.
A disorder characterized by bleeding from the pancreas.
A disorder characterized by bleeding from the prostate gland.
A disorder characterized by bleeding from the spermatic cord.
A disorder characterized by bleeding from the testis.
A disorder characterized by a pathological increase in blood pressure.
A disorder characterized by a decrease in the level of oxygen in the body.
A disorder characterized by bleeding from the ileal wall.
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the ileum.
A disorder characterized by accumulation of iron in the tissues.
A disorder characterized by an abnormal communication between the jejunum and another organ or anatomic site.
A disorder characterized by bleeding from the jejunal wall.
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the jejunum.
Laryngeal edema resulting from a known treatment.
An adverse event characterized by impaired functioning of the left ventricle of the heart during the diastole phase of the cardiac cycle.
Defined in terms of ejection fraction, a good clinical indicator of ventricular systolic function. Normal ejection fraction is 0.50 or more (>50%). Left ventricular systolic dysfunction is generally defined as an ejection fraction equal to or less than 0.40 (<40%).
An adverse event characterized by pain originating in the liver.
A disorder characterized by a cystic lesion containing lymph.
A disorder characterized by inadequate absorption of nutrients in the small intestine. Symptoms include abdominal marked discomfort, bloating and diarrhea.
A disorder characterized by an abnormally low body temperature. Treatment is required when the body temperature is 35C (95F) or below.
A disorder characterized by a dysrhythmia with a heart rate less than 60 beats per minute that originates in the sinus node.
A disorder characterized by inflammation involving the spinal cord. Symptoms include weakness, paresthesia, sensory loss, marked discomfort and incontinence.
A disorder characterized by a necrotic process occurring in the soft tissues of the neck.
Accumulation of substantial excess body fat.
A disorder characterized by an abnormal communication between the pancreas and another organ or anatomic site.
Cecum Perforation that is temporally associated with the use of a medical treatment or procedure, and that may or may not be considered related to the medical treatment or procedure.
A disorder characterized by irritation to the layers of the pericardium (the protective sac around the heart).
A disorder characterized by abnormal presence of air in the pleural cavity resulting in the collapse of the lung.
A disorder characterized by inflammation of the rectum.
An adverse event characterized by an abnormally long interval between the start of the Q wave and the end of the T wave in the heart's electrical cycle, corrected for heart rate.
A disorder characterized by an increase in pressure within the pulmonary circulation due to lung or heart disorder.
A disorder characterized by inhalation of solids or liquids into the lungs.
A disorder characterized by an abnormal communication between the rectum and another organ or anatomic site.
Kidney pain that is temporally associated with the use of a medical treatment or procedure, and that may or may not be considered related to the medical treatment or procedure.
A disorder characterized by progressive and life-threatening pulmonary distress in the absence of an underlying pulmonary condition, usually following major trauma or surgery.
Separation of the inner layers of the retina (neural retina) from the pigment epithelium.
Appendix Perforation that is temporally associated with the use of a medical treatment or procedure, and that may or may not be considered related to the medical treatment or procedure.
A finding of tumor-like collection of serum in the tissues.
An abnormality involving the generation of the action potential by the sinus node and is characterized by an atrial rate inappropriate for physiological requirements. Manifestations include severe sinus bradycardia, sinus pauses or arrest, sinus node exit block, chronic atrial tachyarrhythmias, alternating periods of atrial bradyarrhythmias and tachyarrhythmias, and inappropriate responses of heart rate during exercise or stress.
A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates above the ventricles.
A disorder characterized by an abnormal communication between the trachea and another organ or anatomic site.
Cecum Ulcer that is temporally associated with the use of a medical treatment or procedure, and that may or may not be considered related to the medical treatment or procedure.
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the rectum.
Blockage of the normal flow of urine in the urethra occurring following a procedure or pharmaceutical intervention.
A disorder characterized by inflammation to the uvea of the eye.
A disorder characterized by an abnormal communication between the vagina and another organ or anatomic site.
A disorder characterized by inflammation involving the wall of a vessel.
Premature heartbeats alternating regularly with normal beats. It can be associated with hypoxia, ischemia, acute myocardial infarction, and medication overdose.
A disorder characterized by the reflexive act of ejecting the contents of the stomach through the mouth.
A necrotic process affecting the pharynx.
SCA10 is characterized by slowly progressive cerebellar ataxia that usually starts as poor balance and unsteady gait, followed by upper-limb ataxia, scanning dysarthria, and dysphagia. The disease is exclusively found in Latin American populations, particularly those with Amerindian admixture. Abnormal tracking eye movements are common. Recurrent seizures after the onset of gait ataxia have been reported with variable frequencies among different families. Some individuals have cognitive dysfunction, behavioral disturbances, mood disorders, mild pyramidal signs, and peripheral neuropathy. Onset ranges from age 12 to 48 years.
An elevated urinary concentration of cystathionine.
A transient condition that can occur following influenza vaccination that is characterized by bilateral conjunctivitis, facial edema, and upper respiratory symptoms.
A condition characterized by hyperandrogenism, insulin resistance, and acanthosis nigricans, typically associated with obesity in teenage girls. It is considered to be a subtype of polycystic ovarian syndrome, but may occur in male individuals. Etiology is unclear, but some cases may be associated with mutations affecting the tyrosine kinase domain of the insulin receptor.
A condition of persistent pain and discomfort in the BACK and the LEG following lumbar surgery, often seen in patients enrolled in pain centers.
An abscess that is located in the anatomical space surrounding the liver, but which is outside of the liver capsule itself.
A laboratory test result which indicates increased levels of lipase in a biologic specimen.
A constellation of disorders whose common thread is the insufficient quantity of one or more mitochondrial enzymes.
Punding is a stereotypical motor behavior characterized by an intense fascination with repetitive, excessive and non-goal oriented handling, and examining of objects.
A form of focal dystonia that affects the vocal cords, associated with involuntary contractions of the vocal cords causing interruptions of speech and affecting the voice quality and often leading to patterned, repeated breaks in speech.
A disorder characterized by blockage of the normal flow of the contents of the gallbladder.
A disorder characterized by a dysrhythmia with relatively constant PR interval prior to the block of an atrial impulse. This is the result of intermittent failure of atrial electrical impulse conduction through the atrioventricular (AV) node to the ventricles.
The orally bioavailable potassium salt of a human immunodeficiency virus (HIV) integrase strand transfer inhibitor (HIV-1 INSTI) with HIV-1 antiviral activity. Raltegravir binds to and inhibits integrase, an HIV enzyme that inserts viral genetic material into the genetic material of the infected human cell. Inhibition of integrase prevents insertion of HIV DNA into the human DNA genome, thus blocking HIV replication.
The MECP2 gene is mutated in Rett syndrome (RTT; 312750), a severe neurodevelopmental disorder that almost always occurs in females. Males with non-RTT mutations in the MECP2 gene can demonstrate a wide variety of phenotypes, including X-linked mental retardation with spasticity and other variable features, described here, and Lubs X-linked mental retardation syndrome (MRXSL; 300260). Males with RTT-associated MECP2 mutations have neonatal severe encephalopathy that is usually lethal (300673) (Moog et al., 2003; Villard, 2007).
The MECP2 gene is mutated in Rett syndrome (RTT; 312750), a severe neurodevelopmental disorder that almost always occurs in females. Although it was first thought that MECP2 mutations causing Rett syndrome were lethal in males, later reports identified a severe neonatal encephalopathy in surviving male sibs of patients with Rett syndrome. Since then, additional reports have confirmed a severe phenotype in males with RTT-associated MECP2 mutations (Moog et al., 2003; Villard, 2007). Males with non-RTT mutations in the MECP2 gene can demonstrate a wide variety of phenotypes: see also nonspecific X-linked mental retardation, X-linked mental retardation with spasticity (300055), and X-linked mental retardation due to increased dosage of the MECP2 gene (300260).
The main cause of respiratory distress syndrome (RDS) in premature infants is a developmental deficiency of pulmonary surfactant. The frequency of RDS is inversely proportional to gestational age. However, not all infants born prematurely develop RDS, suggesting that there may be susceptibility factors. Because multiple factors can contribute to the pathogenesis of RDS specifically in premature infants, the etiology is considered to be multifactorial (summaries by Ramet et al., 2000; Clark and Clark, 2005). Pathogenic germline mutations in several genes involved in surfactant metabolism, including SFTPB (178640) and SFTPC (178620), can cause clinical features of respiratory distress syndrome in term neonates, children, and adults, disorders referred to as 'surfactant metabolism dysfunction' (see, e.g., SMDP1, 265120). Susceptibility to the development of RDS in premature infants may be associated with polymorphisms in surfactant genes, such as surfactant protein A1 (SFTPA1; 178630), SFTPB, and SFTPC (see MOLECULAR GENETICS).
Inborn errors of pulmonary surfactant metabolism are genetically heterogeneous disorders resulting in severe respiratory insufficiency or failure in full-term neonates or infants. These disorders are associated with various pathologic entities, including pulmonary alveolar proteinosis (PAP), desquamative interstitial pneumonitis (DIP), or cellular nonspecific interstitial pneumonitis (NSIP) (Clark and Clark, 2005). A clinically similar disorder characterized by respiratory distress (267450) can affect preterm infants, who show developmental deficiency of surfactant. Acquired PAP (610910) is an autoimmune disorder characterized by the presence of autoantobodies to CSF2 (138960). Genetic Heterogeneity of Pulmonary Surfactant Metabolism Dysfunction See also SMDP2 (610913), caused by mutation in the SPTPC gene (178620) on 8p21; SMDP3 (610921), caused by mutation in the ABCA3 gene (601615) on 16p13; SMDP4 (300770), caused by mutation in the CSF2RA gene (306250) on Xp22; and SMDP5 (614370), caused by mutation in the CSF2RB gene (138981) on 22q12.
Autosomal recessive osteopetrosis-5 is a form of infantile malignant osteopetrosis, characterized by defective osteoclast function resulting in decreased bone resorption and generalized osteosclerosis. Defective resorption causes development of densely sclerotic fragile bones and progressive obliteration of the marrow spaces and cranial foramina. Marrow obliteration is associated with extramedullary hematopoiesis and hepatosplenomegaly, and results in anemia and thrombocytopenia, whereas nerve entrapment accounts for progressive blindness and hearing loss. Other major manifestations include failure to thrive, pathologic fractures, and increased infection rate. Most affected children succumb to severe bone marrow failure and overwhelming infection in the first few years of life (Quarello et al., 2004).
A limited ability of the knee joint extension and flexion.
Underdevelopment of the distal portion of the humerus.
A dislocation of the head of the radius from its socket in the elbow joint in an anterolateral direction.
An abnormal conformation of the femur that becomes gradually enlarged towards the proximal end. This feature affects the proximal femoral metaphysis and epiphysis.
DIsruption and breaking up of the basement membrane of the tubules of the kidney.
The presence of multiple cysts at the border between the renal cortex and medulla.
Lack of ossification of the proximal epiphysis of the femur.
Autosomal dominant hyper-IgE recurrent infection syndrome-1 (HIES1; 147060) is a primary immunodeficiency disorder characterized by recurrent Staphylococcus aureus skin abscesses, increased serum IgE, and abnormalities of the connective tissue, skeleton, and dentition (Buckley et al., 1972; Grimbacher et al., 1999). Autosomal recessive HIES2 shares hyper-IgE, eosinophilia, and recurrent Staphylococcal infections, but is distinguished from autosomal dominant HIES1 by the lack of connective tissue and skeletal involvement (Renner et al., 2004). See also TYK2 deficiency (611521), a clinically distinct disease entity that includes characteristic features of both autosomal recessive HIES2 and mendelian susceptibility to mycobacterial disease (MSMD; 209950) (Minegishi et al., 2006). For a discussion of genetic heterogeneity of hyper-IgE recurrent infection syndrome, see 147060.
Developmental hypoplasia of the fallopian tube.
An increased amount of glycogen in muscle tissue.
A pattern of simultaneous degeneration and regeneration of axons (see comment).
Congenital plasminogen deficiency is a rare autosomal recessive disorder characterized clinically by chronic mucosal pseudomembranous lesions consisting of subepithelial fibrin deposition and inflammation. The most common clinical manifestation is ligneous ('wood-like') conjunctivitis, a redness and subsequent formation of pseudomembranes mostly on the palpebral surfaces of the eye that progress to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa. The lesions may be triggered by local injury and/or infection and often recur after local excision. Pseudomembranous lesions of other mucous membranes often occur in the mouth, nasopharynx, trachea, and female genital tract. Some affected children also have congenital occlusive hydrocephalus. A slightly increased female:male ratio has been observed (1.4:1 to 2:1) (Schuster and Seregard, 2003; Tefs et al., 2006). Type I plasminogen deficiency is characterized by decreased serum plasminogen activity, decreased plasminogen antigen levels, and clinical symptoms, whereas type II plasminogen deficiency, also known as 'dysplasminogenemia,' is characterized by decreased plasminogen activity with normal or slightly reduced antigen levels. Patients with type II deficiency are usually asymptomatic. Ligneous conjunctivitis and pseudomembranous formation has only been associated with type I plasminogen deficiency. Presumably, normal amounts of plasminogen antigen with decreased activity, as seen in type II, is sufficient for normal wound healing (Schuster and Seregard, 2003).
Increased anterosuperior prominence of the area between the bottom of the incisura and the inner margin of the antihelix.
Increased width of the distal segment of a finger.
The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid. Total colonic aganglionosis and total intestinal HSCR also occur (Amiel et al., 2008). Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance (Amiel et al., 2008). For a general description and a discussion of genetic heterogeneity of Hirschsprung disease (HSCR), see 142623.
Although primary lateral sclerosis (PLS) is similar to amyotrophic lateral sclerosis (ALS; 105400), they are considered to be clinically distinct progressive paralytic neurodegenerative disorders. Following a period of diagnostic confusion, the clinical distinction between ALS and PLS became clear and diagnostic criteria were established (Pringle et al., 1992). PLS is characterized by degeneration of the upper motor neurons and the corticospinal and corticobulbar tracts, whereas ALS is a more severe disorder characterized by degeneration of both the upper and lower motor neurons. See 606353 for autosomal recessive juvenile-onset PLS, which is caused by mutations in the ALS2 gene (606352).
Hypercortisolemia associated with a primary defect of the adrenal gland leading to overproduction of cortisol.
A preauricular tag is a small excrescence of skin that contains elastic cartilage most commonly located anterior to the tragus, although it can be located on different regions of the ear helix and/or face (Yang et al., 2006). Other synonymous terms include preauricular appendage, accessory tragus (Tunkel, 2007), and less commonly, accessory auricle (Yang et al., 2006).
The presence of whitish deposits in the conjunctiva resembling salt. May be related to calcinosis.
An abnormality related to a defect of vertebral separation of sacral vetebrae during development.
Congenital anomalies of kidney and urinary tract (CAKUT) is a group of abnormalities affecting the kidneys or other structures of the urinary tract. The additional parts of the urinary tract that may be affected include the bladder, the tubes that carry urine from each kidney to the bladder (the ureters), and the tube that carries urine from the bladder out of the body (the urethra). CAKUT results from abnormal development of the urinary system and is present from birth (congenital), although the abnormality may not become apparent until later in life.Individuals with CAKUT have one or more kidney or urinary tract abnormalities. For paired structures, like the kidneys and ureters, one or both may be affected. Many different developmental abnormalities are classified as CAKUT, including underdevelopment or absence of a kidney (renal hypodysplasia or agenesis), a kidney formed of fluid-filled sacs called cysts (multicystic dysplastic kidney), buildup of urine in the kidneys (hydronephrosis), an extra ureter leading to the kidney (duplex kidney or duplicated collecting system), a blockage in a ureter where it joins the kidney (ureteropelvic junction obstruction), an abnormally wide ureter (megaureter), backflow of urine from the bladder into the ureter (vesicoureteral reflux), and an abnormal membrane in the urethra that blocks the flow of urine out of the bladder (posterior urethral valve).CAKUT varies in severity. The abnormalities can result in recurrent urinary tract infections or a buildup of urine in the urinary tract, which may damage the kidneys or other structures. Severe CAKUT can result in life-threatening kidney failure and end-stage renal disease.CAKUT is often one of several features of a condition that affects multiple body systems (syndromic CAKUT). For example, renal coloboma syndrome, 17q12 deletion syndrome, renal cysts and diabetes (RCAD) syndrome, Fraser syndrome, Townes-Brocks syndrome, and branchio-oto-renal syndrome can cause kidney or urinary tract abnormalities in addition to other problems. However, urinary system abnormalities sometimes occur without other signs and symptoms, which is known as nonsyndromic or isolated CAKUT.
Small nodular masses which originate in the subependymal region of the lateral ventricles and protrude into the ventricular cavity. They may represent subependymal hamartomas of tuberous sclerosis or nodular heterotopia of grey matter.
Cortical tubers in the brain are hamartomatous lesions typically located at the gray-white matter interface, commonly in the frontal and parietal lobes. Cortical tubers are composed of abnormal glial and neural cells, and the size, number, and location vary among patients.
Underdevelopment of muscles of the neck.
Underdevelopment of muscles of the shoulder.
The tubulinopathies are a wide and overlapping range of brain malformations caused by mutation of one of seven genes encoding different isotypes of tubulin. Brain malformations include: A range of lissencephalies (classic lissencephaly, lissencephaly with cerebellar hypoplasia, lissencephaly with agenesis of the corpus callosum, and centrally predominant pachygyria), Polymicrogyria-like cortical dysplasia, Simplified gyral pattern, and Microlissencephaly often in combination with dysplastic basal ganglia, corpus callosum abnormalities, and hypoplasia or dysplasia of the brain stem and cerebellum. Clinical features include motor and intellectual disabilities, epilepsy, and ocular findings of varying severity.
Celiac disease, also known as celiac sprue and gluten-sensitive enteropathy, is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins (summary by Farrell and Kelly, 2002). For additional information and a discussion of genetic heterogeneity of celiac disease, see 212750. For a discussion of autoimmunity, see 109100.
SLC4A1-associated distal renal tubular acidosis is a kidney (renal) disorder that sometimes includes blood cell abnormalities. The kidneys normally filter fluid and waste products from the body and remove them in urine; however, in people with distal renal tubular acidosis, the kidneys are unable to remove enough acid from the body, and the blood becomes too acidic. This chemical imbalance is called metabolic acidosis. The inability to remove acids from the body often results in slowed growth and may also lead to softening and weakening of the bones, called rickets in children and osteomalacia in adults. This bone disorder is characterized by bone pain, bowed legs, and difficulty walking. In addition, most children and adults with SLC4A1-associated distal renal tubular acidosis have excess calcium in the urine (hypercalciuria), calcium deposits in the kidneys (nephrocalcinosis), and kidney stones (nephrolithiasis). In rare cases, these kidney abnormalities lead to life-threatening kidney failure. Affected individuals may also have low levels of potassium in the blood (hypokalemia).Individuals with the features described above have complete distal renal tubular acidosis, which usually becomes apparent in childhood. Some people do not develop metabolic acidosis even though their kidneys have trouble removing acids; these individuals are said to have incomplete distal renal tubular acidosis. Additionally, these individuals may have other features of distal renal tubular acidosis, such as bone problems and kidney stones. Often, people who initially have incomplete distal renal tubular acidosis develop metabolic acidosis later in life.Some people with SLC4A1-associated distal renal tubular acidosis also have blood cell abnormalities. These can vary in severity from no symptoms to a condition called hemolytic anemia, in which red blood cells prematurely break down (undergo hemolysis), causing a shortage of red blood cells (anemia). Hemolytic anemia can lead to unusually pale skin (pallor), extreme tiredness (fatigue), shortness of breath (dyspnea), and an enlarged spleen (splenomegaly).There are two forms of SLC4A1-associated distal renal tubular acidosis; they are distinguished by their inheritance pattern. The autosomal dominant form is more common and is usually less severe than the autosomal recessive form. The autosomal dominant form can be associated with incomplete or complete distal renal tubular acidosis and is rarely associated with blood cell abnormalities. The autosomal recessive form is always associated with complete distal renal tubular acidosis and is more commonly associated with blood cell abnormalities, although not everyone with this form has abnormal blood cells.
MDDGC4 is an autosomal recessive muscular dystrophy with onset in infancy or early childhood. Cognition and brain structure are usually normal (Godfrey et al., 2006). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Mercuri et al., 2009).
Meckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver.Other signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia.Because of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure.
Pontocerebellar hypoplasia (PCH) is a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem and associated with severe developmental delay (Edvardson et al., 2007). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
Immunodeficiency-35 is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to localized or disseminated mycobacterial infection after BCG vaccination. Some patients may have increased susceptibility to infection with other intracellular organisms and/or viral infections. Fungal infections are not observed. Laboratory studies show normal levels of immune cells but defective signaling in specific immunologic pathways (summary by Kreins et al., 2015).
The spectrum of CLCN7-related osteopetrosis includes infantile malignant CLCN7-related recessive osteopetrosis (ARO), intermediate autosomal osteopetrosis (IAO), and autosomal dominant osteopetrosis type II (ADOII, Albers-Schönberg disease). Onset of ARO is in infancy. Findings may include: fractures; poor growth; sclerosis of the skull base (with or without choanal stenosis or hydrocephalus) resulting in optic nerve compression, facial palsy, and hearing loss; absence of the bone marrow cavity resulting in severe anemia and thrombocytopenia; dental abnormalities, odontomas, and risk for mandibular osteomyelitis; and hypocalcemia with tetanic seizures and secondary hyperparathyroidism. Without treatment maximal life span in ARO is ten years. Onset of IAO is in childhood. Findings may include fractures after minor trauma, characteristic skeletal radiographic changes found incidentally, mild anemia, and occasional visual impairment secondary to optic nerve compression. Life expectancy in IAO is usually normal. Onset of ADOII is usually late childhood or adolescence. Findings may include: fractures (in any long bone and/or the posterior arch of a vertebra), scoliosis, hip osteoarthritis, and osteomyelitis of the mandible or septic osteitis or osteoarthritis elsewhere. Cranial nerve compression is rare.
The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes.
Shortening of the middle parts of the leg in relation to the upper and terminal segments.
Absence or underdevelopment of the tibia.
A physical quality in which the rib is undulating.
An abnormal reduction in the components of the alternative complement pathway, such as the C3 protein or its cleavage products.
A reduced level of the complement component Factor H in circulation.
Fusion of the hands and feet by a thin membrane of skin (scarring) seen in forms of dystrophic epidermolysis bullosa and leading to a ""mitten"" hand deformity.
A reduction in diameter of the distal phalanx of finger towards the distal end.
An overall widening of the spaces between the digits.
Underdevelopment of the distal epiphysis of the radius.
Calcification, that is, pathological deposition of calcium salts in the arch of aorta.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in the thoracic aorta.
A type of adult onset with onset of symptoms at the age of 40 to 60 years.
A reduction in the ability of the kidneys to remove uric acid from the serum.
A progressive detrimental connective tissue deposition (fibrosis) on the kidney parenchyma involving the tubules and interstitial tissue of the kidney.
The presence of asymmetric developmental dysplasia of the radius.
Short second metacarpal bone because of developmental hypoplasia. [HPO:probinson]
Increased amplitude of the U wave, defined as an amplitude grerater than 1-2mm or 25 percent of the height of the T wave.
Mitochondrial trifunctional protein deficiency is a rare condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting).Signs and symptoms of mitochondrial trifunctional protein deficiency may begin during infancy or later in life. Features that occur during infancy include feeding difficulties, lack of energy (lethargy), low blood sugar (hypoglycemia), weak muscle tone (hypotonia), and liver problems. Infants with this disorder are also at high risk for serious heart problems, breathing difficulties, coma, and sudden death. Signs and symptoms of mitochondrial trifunctional protein deficiency that may begin after infancy include hypotonia, muscle pain, a breakdown of muscle tissue, and a loss of sensation in the extremities (peripheral neuropathy).Problems related to mitochondrial trifunctional protein deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
Demyelination of peripheral motor nerves.
Disproportionate shortening of the proximal segment of the arm (i.e. the humerus).
MBD5 haploinsufficiency is a neurodevelopmental disorder characterized by developmental delay / intellectual disability (ID), severe speech impairment, seizures, sleep disturbances, and abnormal behaviors. Most children lack speech entirely or have single words, short phrases, or short sentences. Seizures are present in about 80%; onset is usually around age two years. Sleep disturbances, present in about 80%, can result in excessive daytime drowsiness. Abnormal behaviors can include autistic-like behaviors (80%) and self-injury and aggression (60%).
Prolonged bleeding post dental extraction sufficient to require medical intervention.
Legius syndrome is characterized by multiple café au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1 (NF1). Additional clinical manifestations reported commonly include intertriginous freckling, lipomas, macrocephaly, and learning disabilities / ADHD / developmental delays. Current knowledge of the natural history of Legius syndrome is based on the clinical manifestations of fewer than 200 individuals with a molecularly confirmed diagnosis; better delineation of the clinical manifestations and natural history of Legius syndrome will likely occur as more affected individuals are identified.
Brachydactyly type B2 (BDB2) is a subtype of brachydactyly characterized by hypoplasia/aplasia of distal phalanges in combination with distal symphalangism, fusion of carpal/tarsal bones, and partial cutaneous syndactyly (summary by Lehmann et al., 2007).
A type of cataract with punctate opacities of the lens.
An abnormality of the shape of vertebrae, such that they are wedge-shaped (narrow towards the back).
Increased height of the wing (or ala) of the ilium (which is the large expanded portion which bounds the greater pelvis laterally).
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypical, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of genetic heterogeneity of autism, see 209850.
In healthy adults, fetal hemoglobin (HbF) is present at residual levels (less than 0.06% of total hemoglobin) with over 20-fold variation. Ten to fifteen percent of adults fall within the upper tail of the distribution and have HbF levels between 0.8% and 5%, a condition referred to as heterocellular hereditary persistence of fetal hemoglobin Although these HbF levels are modest in otherwise healthy individuals, interaction of heterocellular HPFH with beta-thalassemia (see 613985) or sickle cell disease (SS; 603903) can increase HbF output in these individuals to levels that are clinically beneficial (Menzel et al., 2007). For a general phenotypic description and a discussion of loci that may affect fetal hemoglobin levels, see HBFQTL1 (141749).
Persistent hyperplastic primary vitreous (PHPV), also termed 'persistent fetal vasculature,' is a developmental malformation of the eye in which the primary vitreous fails to regress in utero, resulting in the presence of a retrolental fibrovascular membrane with persistence of the posterior portion of the tunica vasculosa lentis and hyaloid artery. This abnormality is usually unilateral and associated with microphthalmia, cataract, glaucoma, and congenital retinal nonattachment (see Haddad et al., 1978; Khaliq et al., 2001; Prasov et al., 2012). PHPV shares phenotypic overlap with Norrie disease (310600). Genetic Heterogeneity of Persistent Hyperplastic Primary Vitreous A dominant form of PHPV has been described (PHPVAD; 611308).
Persistent hyperplastic primary vitreous (PHPV) is a developmental malformation of the eye due to the presence of a retrolental fibrovascular membrane with persistence of the posterior portion of the tunica vasculosa lentis and hyaloid artery. This abnormality is usually unilateral and associated with microphthalmos, cataract, and glaucoma (Haddad et al., 1978). For a discussion of genetic heterogeneity of PHPV, see 221900.
The spectrum of ANO5-related muscle diseases is a continuum that ranges from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. The most typical presentation is limb-girdle muscular dystrophy type 2L (LGMD2L) with late-onset proximal lower-limb weakness (mean onset age 35 years; range 15-70 years). Less common is Miyoshi-like disease or Miyoshi muscular dystrophy 3 with early-adult-onset calf distal myopathy (age 20 to 25 years). Incidental hyperCKemia may be present even earlier. Females have milder disease manifestations than males. Initial symptoms are walking difficulties, reduced sports performance, and difficulties in standing on toes as well as nonspecific exercise myalgia and/or burning sensation in the calf muscles. Muscle weakness and atrophy are frequently asymmetric. Bulbar or respiratory symptoms have not been reported. Disease progression is slow in both the LGMD and distal forms; ambulation is preserved until very late in the disease course.
Autosomal recessive spastic ataxia is a neurologic disorder characterized by onset in the first 2 decades of cerebellar ataxia, dysarthria, and variable spasticity of the lower limbs. Cognition is not affected (summary by Dor et al., 2014). For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600).
Isobutyryl-CoA dehydrogenase (IBD) deficiency is a condition that disrupts the breakdown of certain proteins. Normally, proteins from food are broken down into parts called amino acids. Amino acids can be further processed to provide energy for growth and development. People with IBD deficiency have inadequate levels of an enzyme that helps break down a particular amino acid called valine.Most people with IBD deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. A few children with IBD deficiency have developed features such as a weakened and enlarged heart (dilated cardiomyopathy), weak muscle tone (hypotonia), and developmental delay. This condition may also cause low numbers of red blood cells (anemia) and very low blood levels of carnitine, which is a natural substance that helps convert certain foods into energy. The range of signs and symptoms associated with IBD deficiency remains unclear because very few affected individuals have been reported.
A contrqacture (chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin) that prevent normal movement of one or more joints of the limbs.
FRA12A is a folate-sensitive chromosomal fragile site prone to breakage. No consistent phenotype has been observed with FRA12A, and it can be inherited without phenotypic effect (Berg et al., 2000). However, mental retardation with or without other anomalies has been described in patients with over 40% of cells expressing FRA12A (Winnepenninckx et al., 2007).
Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003). For additional information and a discussion of genetic heterogeneity of restless legs syndrome (RLS), see RLS1 (102300).
Charcot-Marie-Tooth neuropathy type 4J (CMT4J) is a peripheral neuropathy characterized by childhood onset (manifest as clumsy gait) with accelerated limb weakness and muscle atrophy during the teen or adult years that is typically asymmetric and can involve both distal and proximal limb muscles. Although sensory symptoms are minimal, examination may reveal decreased response to touch, pin prick, or vibration distally. Bulbar and cranial nerve functions are often spared; intellect is normal.
Restless legs syndrome (RLS) is a neurologic disorder characterized by an uncontrollable urge to move the legs during periods of rest. The majority of patients with RLS also have periodic limb movements in sleep, which are characterized by involuntary, highly stereotypical, regularly occurring limb movements that occur during sleep. Limb movements during sleep are more common in otherwise asymptomatic family members of patients with RLS compared to the general population (Stefansson et al., 2007). Thus, periodic limb movements during sleep may serve as an endophenotype for RLS. However, not all patients with RLS have limb movements during sleep, and the majority of individuals with limb movements during sleep do not have waking symptoms of RLS (Winkelman, 2007). For additional information and a discussion of genetic heterogeneity of RLS, see RLS1 (102300).
Syndrome with characteristics of severe psychomotor retardation, failure to thrive and intolerance to wheat and dairy products. So far, only two cases have been described. The disease is caused by mutations in the COG8 gene, which encodes a subunit of the COG complex. This complex is involved vesicle transport in the Golgi apparatus.
Malaria, a major cause of child mortality worldwide, is caused by mosquito-borne hematoprotozoan parasites of the genus Plasmodium. Of the 4 species that infect humans, P. falciparum causes the most severe forms of malaria and is the major cause of death and disease. Although less fatal, P. malariae, P. ovale, and, in particular, P. vivax infections are major causes of morbidity. The parasite cycle involves a first stage in liver cells and a subsequent stage at erythrocytes, when malaria symptoms occur. A wide spectrum of phenotypes are observed, from asymptomatic infection to mild disease, including fever and mild anemia, to severe disease, including cerebral malaria, profound anemia, and respiratory distress. Genetic factors influence the response to infection, as well as disease progression and severity. Malaria is the strongest known selective pressure in the recent history of the human genome, and it is the evolutionary driving force behind sickle-cell disease (603903), thalassemia (see 141800), glucose-6-phosphatase deficiency (300908), and other erythrocyte defects that together constitute the most common mendelian diseases of humans (Kwiatkowski, 2005; Campino et al., 2006).
Aromatase excess syndrome is an autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females (Tiulpakov et al., 2005).
A developmental defect resulting in the congenital absence of skin on the scalp vertex, often just lateral to the midline.
Angioma serpiginosum is an uncommon benign skin disorder characterized by asymptomatic clusters of nonpurpuric punctate erythematous lesions. The rash is asymptomatic but may lead to cosmetic problems and can be treated by laser therapy. Women are most commonly affected, and the disorder is most often sporadic, although rare families suggestive of autosomal dominant inheritance have been reported (Sandhu and Gupta, 2005). No male-to-male transmission has been described, but father-to-daughter transmissions are known. It has been suggested that the pattern of skin involvement may be due to cutaneous somatic mosaicism (Chen et al., 2006; Blinkenberg et al., 2007). An X-linked dominant form of angioma serpiginosum (300652) has been mapped. The few males described may actually represent somatic mosaicism of an X-linked gene.
Familial paroxysmal nonkinesigenic dyskinesia is a disorder of the nervous system that causes episodes of involuntary movement. Paroxysmal indicates that the abnormal movements come and go over time. Nonkinesigenic means that episodes are not triggered by sudden movement. Dyskinesia broadly refers to involuntary movement of the body.People with familial paroxysmal nonkinesigenic dyskinesia experience episodes of abnormal movement that are brought on by alcohol, caffeine, stress, fatigue, menses, or excitement or develop without a known cause. Episodes are not induced by exercise or sudden movement and do not occur during sleep. An episode is characterized by irregular, jerking or shaking movements that range from mild to severe. In this disorder, the dyskinesia can include slow, prolonged contraction of muscles (dystonia); small, fast, ""dance-like"" motions (chorea); writhing movements of the limbs (athetosis); and, rarely, flailing movements of the limbs (ballismus). The dyskinesia also affects muscles in the torso and face. The type of abnormal movement varies among affected individuals, even among affected members of the same family. Individuals with familial paroxysmal nonkinesigenic dyskinesia do not lose consciousness during an episode. Most people do not experience any neurological symptoms between episodes.Individuals with familial paroxysmal nonkinesigenic dyskinesia usually begin to show signs and symptoms of the disorder during childhood or their early teens. Episodes typically last 1 to 4 hours, and the frequency of episodes ranges from several per day to one per year. In some affected individuals, episodes occur less often with age.
Meckel syndrome is an autosomal recessive pre- or perinatal lethal disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically occipital encephalocele), hepatic ductal dysplasia and cysts, and postaxial polydactyly (summary by Baala et al., 2007). For a more complete phenotypic description and information on genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
MC1DN20 is an autosomal recessive multisystem disorder characterized by infantile onset of acute metabolic acidosis, hypertrophic cardiomyopathy, and muscle weakness associated with a deficiency of mitochondrial complex I activity in muscle, liver, and fibroblasts (summary by Haack et al., 2010). For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010.
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is characterized by slowly progressive cerebellar ataxia and spasticity with dorsal column dysfunction (decreased position and vibration sense) in most patients. The neurologic dysfunction involves the legs more than the arms. The tendon reflexes are retained. Deterioration of motor skills usually starts in childhood or adolescence, but occasionally not until adulthood. Dysarthria develops over time. Occasional findings include: epilepsy; learning problems; cognitive decline; and reduced consciousness, neurologic deterioration, and fever following minor head trauma. Many affected individuals become wheelchair dependent in their teens or twenties. Neonatal or early-infantile onset patients have a severe disease course and may die, whereas late-infantile and early-childhood onset is associated with early wheelchair dependency.
CATSPER-related male infertility results from abnormalities in sperm and can be either CATSPER-related nonsyndromic male infertility (NSMI) or the deafness-infertility syndrome (DIS) when associated with non-progressive prelingual sensorineural hearing loss. Males with NSMI have infertility while females have no symptoms. Males with DIS have both infertility and hearing loss, while females have only hearing loss. Routine semen analysis typically identifies abnormalities in sperm number, morphology, and motility. Otologic examination and audiologic assessment can identify hearing loss.
Hereditary gingival fibromatosis is a benign disorder manifested by a slowly progressive overgrowth of the oral gingival tissues, which results in the teeth being partially or totally engulfed by keratinized gingiva (summary by Zhu et al., 2007). For general phenotypic information and a discussion of genetic heterogeneity of hereditary gingival fibromatosis, see GINGF1 (135300).
Deficiency of phosphoserine aminotransferase (PSAT) is characterized biochemically by low plasma and cerebrospinal fluid (CSF) concentrations of serine and glycine and clinically by intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation. Outcome is poor once the individual becomes symptomatic, but treatment with serine and glycine supplementation from birth can lead to a normal outcome (Hart et al., 2007).
A reduced level of the complement component Factor I in circulation.
Recurrent infections by Neisseria meningitidis (one of the most common causes of bacterial meningitis), which is also known as meningococcus.
Progressive familial heart block is a genetic condition that alters the normal beating of the heart. A normal heartbeat is controlled by electrical signals that move through the heart in a highly coordinated way. These signals begin in a specialized cluster of cells called the sinoatrial node (the heart's natural pacemaker) located in the heart's upper chambers (the atria). From there, a group of cells called the atrioventricular node carries the electrical signals to another cluster of cells called the bundle of His. This bundle separates into multiple thin spindles called bundle branches, which carry electrical signals into the heart's lower chambers (the ventricles). Electrical impulses move from the sinoatrial node down to the bundle branches, stimulating a normal heartbeat in which the ventricles contract slightly later than the atria.Heart block occurs when the electrical signaling is obstructed anywhere from the atria to the ventricles. In people with progressive familial heart block, the condition worsens over time: early in the disorder, the electrical signals are partially blocked, but the block eventually becomes complete, preventing any signals from passing through the heart. Partial heart block causes a slow or irregular heartbeat (bradycardia or arrhythmia, respectively), and can lead to the buildup of scar tissue (fibrosis) in the cells that carry electrical impulses. Fibrosis contributes to the development of complete heart block, resulting in uncoordinated electrical signaling between the atria and the ventricles and inefficient pumping of blood in the heart. Complete heart block can cause a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, fainting (syncope), or sudden cardiac arrest and death.Progressive familial heart block can be divided into type I and type II, with type I being further divided into types IA and IB. These types differ in where in the heart signaling is interrupted and the genetic cause. In types IA and IB, the heart block originates in the bundle branch, and in type II, the heart block originates in the atrioventricular node. The different types of progressive familial heart block have similar signs and symptoms.Most cases of heart block are not genetic and are not considered progressive familial heart block. The most common cause of heart block is fibrosis of the heart, which occurs as a normal process of aging. Other causes of heart block can include the use of certain medications or an infection of the heart tissue.
Agenesis specifically affecting one of the classes incisor, premolar, or molar.
An extremely rare form of carbohydrate deficient glycoprotein syndrome characterised clinically in the single reported case by repeated haemorrhagic incidents, including severe pulmonary haemorrhage.
Pitt-Hopkins syndrome (PTHS) is characterized by significant developmental delays with moderate-to-severe intellectual disability and behavioral differences, characteristic facial features, and episodic hyperventilation and/or breath-holding while awake. Speech is significantly delayed and most individuals are nonverbal with receptive language often stronger than expressive language. Other common findings are autism spectrum disorder symptoms, sleep disturbance, stereotypic hand movements, seizures, constipation, and severe myopia.
For a general phenotypic description and a discussion of genetic heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1 (265120).
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most forms of OI are autosomal dominant with mutations in one of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Cabral et al. (2007) described a form of autosomal recessive OI, which they designated OI type VIII, characterized by white sclerae, severe growth deficiency, extreme skeletal undermineralization, and bulbous metaphyses.
Surfactant protein C (SPC) deficiency is a rare autosomal dominant disease associated with progressive respiratory insufficiency and lung disease with a variable clinical course. The pathophysiology of the disorder is postulated to involve intracellular accumulation of a structurally defective SPC protein (Thomas et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1 (265120).
Pulmonary alveolar proteinosis is a pathologic entity characterized by intraalveolar surfactant accumulation. There are 3 clinically distinct forms: hereditary (usually congenital), secondary, and acquired. The acquired form of pulmonary alveolar proteinosis is the most common form, accounting for approximately 90% of cases. The mean age at diagnosis is 39 years and it is associated with smoking in 72% of cases. The estimated incidence and prevalence are 0.36 and 3.70 cases per million, respectively (Trapnell et al., 2003; Seymour and Presneill, 2002). Secondary pulmonary alveolar proteinosis develops in association with conditions involving functional impairment or reduced numbers of alveolar macrophages. Such conditions include some hematologic cancers, pharmacologic immunosuppression, inhalation of inorganic dust or toxic fumes, and certain infections. Congenital pulmonary alveolar proteinosis is a rare, severe, often fatal disorder of newborns associated with pulmonary surfactant metabolism dysfunction caused by mutations in genes involved in surfactant metabolism (see, e.g., SMDP1, 265120) (Trapnell et al., 2003). See 300770 for information on congenital PAP due to CSF2RA (306250) deficiency.
Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis (Laitinen et al., 2001; Illig and Wjst, 2002). For a general phenotypic description and a discussion of genetic heterogeneity of asthma, see 600807, and of allergic rhinitis, see 607154.
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals and is a heritable trait (summary by Perry et al., 2014). Genetic Heterogeneity of Age at Menarche Age at menarche has been associated with variation on chromosome 22q13. Other quantitative trait loci (QTLs) associated with age at menarche include MENAQ2 (612882) on chromosome 6q21 and MENAQ3 (612883) on chromosome 9q31.
An crumpled radiographic appearance of the long bones, as is the long bone had been crushed together producing irregularities. This feature is the result of multiple fractures and repeated rounds of ineffective healing, as can be seen for instance in severe forms of osteogenesis imperfecta.
An abnormality of the reflex that controls the diameter of the pupil, in response to the intensity of light that falls on the retina of the eye.
Multiple endocrine neoplasia is a group of disorders that affect the body's network of hormone-producing glands called the endocrine system. Hormones are chemical messengers that travel through the bloodstream and regulate the function of cells and tissues throughout the body. Multiple endocrine neoplasia typically involves tumors (neoplasia) in at least two endocrine glands; tumors can also develop in other organs and tissues. These growths can be noncancerous (benign) or cancerous (malignant). If the tumors become cancerous, the condition can be life-threatening.The major forms of multiple endocrine neoplasia are called type 1, type 2, and type 4. These types are distinguished by the genes involved, the types of hormones made, and the characteristic signs and symptoms.Many different types of tumors are associated with multiple endocrine neoplasia. Type 1 frequently involves tumors of the parathyroid glands, the pituitary gland, and the pancreas. Tumors in these glands can lead to the overproduction of hormones. The most common sign of multiple endocrine neoplasia type 1 is overactivity of the parathyroid glands (hyperparathyroidism). Hyperparathyroidism disrupts the normal balance of calcium in the blood, which can lead to kidney stones, thinning of bones, nausea and vomiting, high blood pressure (hypertension), weakness, and fatigue.The most common sign of multiple endocrine neoplasia type 2 is a form of thyroid cancer called medullary thyroid carcinoma. Some people with this disorder also develop a pheochromocytoma, which is an adrenal gland tumor that can cause dangerously high blood pressure. Multiple endocrine neoplasia type 2 is divided into three subtypes: type 2A, type 2B (formerly called type 3), and familial medullary thyroid carcinoma (FMTC). These subtypes differ in their characteristic signs and symptoms and risk of specific tumors; for example, hyperparathyroidism occurs only in type 2A, and medullary thyroid carcinoma is the only feature of FMTC. The signs and symptoms of multiple endocrine neoplasia type 2 are relatively consistent within any one family.Multiple endocrine neoplasia type 4 appears to have signs and symptoms similar to those of type 1, although it is caused by mutations in a different gene. Hyperparathyroidism is the most common feature, followed by tumors of the pituitary gland, additional endocrine glands, and other organs.
Phosphoribosylpyrophosphate synthetase (PRS) superactivity is characterized by hyperuricemia and hyperuricosuria and is divided into a severe phenotype with infantile or early-childhood onset and a milder phenotype with late-juvenile or early-adult onset. Variable combinations of sensorineural hearing loss, hypotonia, and ataxia observed in the severe type are not usually present in the mild type. In the mild type, uric acid crystalluria or a urinary stone is commonly the first clinical finding, followed later by gouty arthritis if serum urate concentration is not controlled.
Phosphoglycerate kinase-1 deficiency is an X-linked recessive condition with a highly variable clinical phenotype that includes hemolytic anemia, myopathy, and neurologic involvement. Patients can express 1, 2, or all 3 of these manifestations (Shirakawa et al., 2006).
IMD34 results in predisposition to infections by poorly virulent mycobacteria, such as bacillus Calmette-Guerin (BCG) vaccines and nontuberculous environmental bacteria. Affected individuals are also susceptible to the more virulent species Mycobacterium tuberculosis (Bustamante et al., 2007).
IMD33 results from X-linked recessive NEMO deficiency, which is associated with various other diseases, including immunodeficiency with hypohidrotic ectodermal dysplasia (300291), together with osteopetrosis and lymphedema (300301) in some patients, and immunodeficiency without ectodermal dysplasia (300584). In contrast with patients with these other forms of X-linked recessive NEMO deficiency, who display a broad susceptibility to infections, infections in IMD33 patients are mostly limited to mycobacterial disease, with M. avium complex being the most common cause. Furthermore, IMD33 patients lack developmental features suggestive of hypohidrotic ectodermal dysplasia. Monocytes from IMD33 patients have intrinsic defects in T cell-dependent IL12 (see 161561) production, resulting in impaired IFNG (147570) production. The prognosis of IMD33 patients is variable (review by Al-Muhsen and Casanova, 2008).
A commercial combination preparation containing guaifenesin and phenylephrine hydrochloride with expectorant and decongestant activities. Guaifenesin works by drawing water into respiratory tracts, thereby reducing adhesiveness and surface tension of mucus as well as increasing hydration of mucus. This reduces the viscosity of mucus and makes the cough more productive. Phenylephrine hydrochloride, a direct-acting sympathicomimetic amine, activates alpha-adrenergic receptors in the nasal mucosa thereby causing vasoconstriction, reduces swelling of nasal mucous membranes and decreases nasal and sinus congestion.
The state of a subject that represents to what extent they have abstained from consuming food or liquid.
Derivatives of BUTYRIC ACID that contain one or more amino groups attached to the aliphatic structure. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the aminobutryrate structure.
Presence of nodules in the conjunctiva of the eye.
Failure to thrive (FTT), that occurs in less than five percent of FTT cases; it is caused by acute or chronic disorders that interfere with nutritional uptake, including cleft palate, malabsorption due to cystic fibrosis, and short gut syndrome.
A grade I or grade II glioma arising from the central nervous system. This category includes pilocytic astrocytoma, diffuse astrocytoma, subependymal giant cell astrocytoma, ependymoma, oligodendroglioma, oligoastrocytoma, and angiocentric glioma.
Pain associated with a damaged PUDENDAL NERVE. Clinical features may include positional pain with sitting in the perineal and genital areas, sexual dysfunction and FECAL INCONTINENCE and URINARY INCONTINENCE.
An electrocardiographic finding of J point and ST segment elevation in the absence of other signs of acute ischemia or pericarditis. (CDISC)
Bladder sphincter dysfunction in an individual with normal bladder innervation, which may lead to renal impairment.
The hydrochloride salt of the synthetic high-affinity transition-state analogue forodesine. Forodesine binds preferentially to and inhibits purine nucleotide phosphorylase (PNP), resulting in the accumulation of deoxyguanosine triphosphate and the subsequent inhibition of the enzyme ribonucleoside diphosphate reductase and DNA synthesis. This agent selectively causes apoptosis in stimulated or malignant T-lymphocytes. A transition state analogue is a substrate designed to mimic the properties or the geometry of the transition state of reaction.
Large or prominent malar surface of the zygomatic bone of the skull, which is convex and forms the prominence of the 'cheek bones'.
A recombinant form of the endogenous human cytokine erythropoietin (EPO) with erythropoiesis-stimulating activity. Similar to EPO, epoetin zeta binds to and activates erythropoietin receptors on the surface of committed erythroid progenitors in the bone marrow resulting in their proliferation and differentiation into functional erythrocytes. This may enhance red blood cell counts and hemoglobin levels. Epoetin zeta differs from other epoetins in its glycosylation profile. EPO is a glycosylated polypeptide primarily produced by renal peritubular cells and its synthesis is regulated by a serum oxygenation feedback mechanism.
Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.
A cinnamic hydroxamic acid analogue with potential antineoplastic activity. Panobinostat selectively inhibits histone deacetylase (HDAC), inducing hyperacetylation of core histone proteins, which may result in modulation of cell cycle protein expression, cell cycle arrest in the G2/M phase and apoptosis. In addition, this agent appears to modulate the expression of angiogenesis-related genes, such as hypoxia-inducible factor-1alpha (HIF-1a) and vascular endothelial growth factor (VEGF), thus impairing endothelial cell chemotaxis and invasion. HDAC is an enzyme that deacetylates chromatin histone proteins.
A periodic beat-to-beat variation in the amplitude or shape of the T wave in an EKG.
A radiopharmaceutical composed of ammonia labeled with the radioisotope nitrogen N 13 that can be used, during positron emission tomography (PET), as a blood flow imaging agent and potentially as a tumor imaging agent. Upon intravenous administration, ammonia N 13 distributes to various organs in the body, such as the myocardium, liver, kidneys and brain. This agent is taken up by cells and is retained following conversion to glutamine N 13 by glutamine synthetase (GS). Upon PET, organ perfusion and the presence of cancer cells can be assessed. GS, an enzyme that catalyzes the synthesis of glutamine from glutamate and ammonia, is overexpressed in a variety of cancers and plays a key role in cancer cell proliferation.
Change in or modification of the gastrointestinal system
Increased chance of more than adequate intake or absorption of food or,nutrients
Difficulty in fulfilling care responsibilities, expectations and/or behaviors for family or significant others.
Absence of cognitive information related to a specific topic, or its acquisition.
Inability to independently maintain a safe growth-promoting immediate environment.
Impaired ability to clothe and groom oneself
Impaired ability to urinate or defecate for oneself
Decrease in the ability to guard self from internal or external threats such as illness or injury.
Change in or modification of personal identity
A pattern of invalid appraisal of stressors, with cognitive and/or behavioral efforts, that fails to manage demands related to well-being.
Imbalance in the normal feeding habits of an infant
Inability to adjust to lowered levels of mechanical ventilator support that interrupts and prolongs the weaning process.
Inability to initiate and/or maintain independent breathing that is adequate to support life.
Parental experience of role confusion and conflict in response to crisis.
A pattern of nutrient intake, which can be strengthened.
A pattern of providing an environment for children to nurture growth and development, which can be strengthened.
A disorder characterized by melancholic feelings of grief or unhappiness.
An adenosine triphosphate analogue and reversible P2Y12 PURINORECEPTOR antagonist that inhibits ADP-mediated PLATELET AGGREGATION. It is used for the prevention of THROMBOEMBOLISM by patients with ACUTE CORONARY SYNDROME or a history of MYOCARDIAL INFARCTION.
An orally active aqueous extract derived from the plant Scutellaria barbata with potential antineoplastic activity. Sparing normal cells, apoptosis inducer BZL101 specifically facilitates translocation of the protein apoptosis-inducing factor (AIF) from the mitochondrial membrane into the nucleus in tumor cells, thereby causing tumor cell-specific chromatin condensation and DNA degradation followed by the induction of caspase-independent apoptosis. AIF is both a mitochondrial intermembrane flavoprotein with oxidoreductase activity and a caspase-independent death effector that, similar to cytochrome c, is released from mitochondria early in the apoptotic process.
A synthetic, fourteen amino acid peptide and agonist of intestinal guanylate cyclase type C (GC-C), which is structurally related to the guanylin peptide family, with secretagogue, analgesic and laxative activities. Upon oral administration, linaclotide binds to and activates GC-C receptors located on the luminal surface of the intestinal epithelium. This increases the concentration of intracellular cyclic guanosine monophosphate (cGMP), which is derived from guanosine triphosphate (GTP). cGMP activates the cystic fibrosis transmembrane conductance regulator (CFTR) and stimulates the secretion of chloride and bicarbonate into the intestinal lumen. This promotes sodium excretion into the lumen and results in increased intestinal fluid secretion. This ultimately accelerates GI transit of intestinal contents, improves bowel movement and relieves constipation. Increased extracellular cGMP levels may also exert an antinociceptive effect, through an as of yet not fully elucidated mechanism, that may involve modulation of nociceptors found on colonic afferent pain fibers. Linaclotide is minimally absorbed from the GI tract.
An orally bioavailable synthetic retinoid X receptor (RXR) agonist with potential antineoplastic and anti-inflammatory activities. Rexinoid NRX 194204 selectively binds to and activates RXRs. Because RXRs can form heterodimers with several nuclear receptors (NRs), RXR activation by this agent may result in a broad range of gene expression depending on the effector DNA response elements activated. Rexinoid NRX 194204 may inhibit the tumor-necrosis factor (TNF)-mediated release of nitric oxide (NO) and interleukin 6 (IL6) and may inhibit tumor cell proliferation. This agent appears to be less toxic than RAR-selective ligands.
An opioid analgesic, MU OPIOID RECEPTOR agonist, and noradrenaline reuptake inhibitor that is used in the treatment of moderate to severe pain, and of pain associated with DIABETIC NEUROPATHIES.
A synthetic, orally bioavailable, small-molecule ghrelin mimetic with appetite-stimulating and anabolic activities. RC-1291 ghrelin mimetic binds to and stimulates the growth hormone secretagogue receptor (GHSR) centrally, thereby mimicking the appetite-stimulating and growth hormone-releasing effects of grhelin. Stimulation of GHSR may also reduce the production of the pro-inflammatory cytokines TNF-alpha and interleukin-6, which may play a direct role in cancer-related loss of appetite. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=460131&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=460131&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C52197"" NCI Thesaurus)
An orally available phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity. Upon oral administration, AR-42 inhibits the catalytic activity of HDAC, which results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibits tumor cell division and induces tumor cell apoptosis. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins.
An epoxomicin derivate with potential antineoplastic activity. Carfilzomib irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S catalytic core subunit of the proteasome, a protease complex responsible for degrading a large variety of cellular proteins. Inhibition of proteasome-mediated proteolysis results in an accumulation of polyubiquinated proteins, which may lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor growth.
A proprietary formulation of resveratrol, a polyphenolic phytoalexin derived from grapes and other food products with potential antioxidant, anti-obesity, antidiabetic and chemopreventive activities. Resveratrol may activate sirtuin subtype 1 (SIRT-1). SIRT1 activation has been reported to inhibit tumorigenesis and tumor cell proliferation. SIRT-1 is a member of the silent information regulator 2 (SIR2) (or sirtuin) family of enzymes that plays an important role in mitochondrial activity and acts as a protein deacetylase. SIRT1 appears to be involved in the regulation of numerous transcription factors such as NF-kB and p53.
A quinazoline derivative with potential antineoplastic activities. Verubulin binds to and inhibits tubulin polymerization and interrupts microtubule formation, resulting in disruption of mitotic spindle assembly, cell cycle arrest in the G2/M phase, and cell death. This agent is not a substrate for several subtypes of multidrug resistance ABC transporters, and may be useful for treating multidrug resistant tumors. In addition, as a vascular disrupting agent, verubulin disrupts tumor microvasculature specifically, which may result in acute ischemia and massive tumor cell death. In addition, verubulin is able to cross the blood-brain barrier and accumulate in the brain.
A rationally designed, orally available, Class 1-selective, small molecule, 2-aminobenzamide HDAC inhibitor with potential antineoplastic activity. Mocetinostat binds to and inhibits Class 1 isoforms of HDAC, specifically HDAC 1, 2 and 3, which may result in epigenetic changes in tumor cells and so tumor cell death; although the exact mechanism has yet to be defined, tumor cell death may occur through the induction of apoptosis, differentiation, cell cycle arrest, inhibition of DNA repair, upregulation of tumor suppressors, down regulation of growth factors, oxidative stress, and autophagy, among others. Overexpression of Class I HDACs 1, 2 and 3 has been found in many tumors and has been correlated with a poor prognosis.
Vitamin K-dependent protein S (676 aa, ~75 kDa) is encoded by the human PROS1 gene. This protein plays a role in coagulation regulation.
A recombinant sialidase fusion protein composed of a sialidase catalytic domain derived from Actinomyces viscosus, a constituent of the normal oral and gastrointestinal flora in humans, fused to a cell surface-anchoring domain, with potential anti-viral activity. Following administration by oral inhalation, DAS181 proteolytically removes sialic acid from the airway epithelium, which inhibits viral binding to and internalization by cells of the respiratory epithelium and prevents viral replication. The cell surface anchoring-domain of this agent may increase retention time and drug potency. Sialic acids in the respiratory tract are used by influenza and parainfluenza viruses to invade airway epithelial cells.
The aggregate of past events; the continuum of events occurring in succession leading from the past to the present; a record or narrative description of past events.
An adverse event resulting in a change in a patient's intellectual capacity, emotional state, or general mental health.
A synthetic heterocyclic carboxaldehyde thiosemicarbazone with potential antineoplastic activity. Triapine inhibits the enzyme ribonucleotide reductase, resulting in the inhibition of the conversion of ribonucleoside diphosphates to deoxyribonucleotides necessary for DNA synthesis. This agent has been shown to inhibit tumor growth in vitro. (NCI04)
Disease of the large or small intestine that is caused by inadequate blood supply.
A type of cirrhosis characterized by the presence of large regenerative nodules.
A benign melanocytic proliferation within or adjacent to the optic disk. It presents as a pigmented, intraocular tumor.
The method by which conception or impregnation is prevented. This may be achieved through the use of devices, drugs or surgery.
An increase in nuclear size and amount of cytoplasm of a cell. The cells or nucleus may be slightly irregular and/or may be polyploid.
Recurrent or persistent involuntary SPASM of the outer muscles of the VAGINA, occurring during vaginal penetration.
Backward flow of refluxed gastric content into the mouth or hypopharynx.
A permanent mark left on the skin in the process of wound healing.
A malignant disease of the B-LYMPHOCYTES in the bone marrow and/or blood.
A primary malignant neoplasm of the vagina composed of malignant melanocytes.
Usually, three large arteries arise from the arch of the aorta: the brachiocephalic trunk (divided into the right common carotid artery and the right subclavian artery), the left common carotid artery, and the left subclavian artery. However, when aberrant right subclavian artery variant is present, the brachiocephalic trunk is absent and four large arteries arise from the arch of the aorta: the right common carotid artery, the left common carotid artery, the left subclavian artery, and the final one with the most distal left sided origin, the right subclavian artery, also called the arteria lusoria.
A rare variant of undifferentiated pancreatic carcinoma characterized by the presence of non-neoplastic osteoclast-like giant cells.
A carcinoma that arises from the extrahepatic bile ducts and it is characterized by the presence of a sarcomatous component.
A carcinoma that arises from the gallbladder and it is characterized by the presence of a sarcomatous component. The sarcomatous component may contain osteosarcoma, chondrosarcoma, or rhabdomyosarcoma elements.
An aggressive carcinoma with a sarcomatous component that arises from the liver. The sarcomatous component is clonally related to the more differentiated, carcinomatous component. The prognosis is usually poor.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the gallbladder. It is characterized by the presence of malignant large cells.
A supratentorial primitive neuroectodermal tumor characterized by the presence of poorly differentiated or undifferentiated neuroepithelial cells and ganglion cells.
Inflammation of the stomach resulting in bleeding.
A rare undifferentiated carcinoma that arises from the larynx. It is characterized by the presence of multiple bizarre multinucleated giant cells. The prognosis is poor.
Negative, defiant, or hostile behavior directed towards authority.
Multiple fetuses birthed live or dead in a single pregnancy regardless of gestational age, and regardless of whether the fetuses were birthed on different dates.
Reduced number or density of facial hair.
Sarcomatoid (spindle cell) carcinomas of the tongue is a variant of squamous carcinoma of tongue that is monoclonal, having evolved from a conventional squamous carcinoma with dedifferentiation associated with sarcomatoid transformation.
A usually high grade squamous cell carcinoma that arises from the ovary and is not associated with a germ cell tumor. The prognosis is poor.
The relationship of the presenting part of the fetus to the maternal ischial spines during labor and delivery.
Group B Streptococcus, also known as Streptococcus agalactiae, colonizes the vaginal and gastrointestinal tracts of up to 45% of healthy women and may infect neonates in utero or during delivery, causing neonatal sepsis in 1-2% of colonized neonates. GBS infection may also occur in nonpregnant (particularly elderly) adults with underlying medical conditions, presenting as urinary tract infection, pneumonia, or soft-tissue infection.
Carious lesion of any cervical (gingival) or other smooth surface area of tooth.
A type of Congenital cataract in which the opacities occupy the subcapsular cortex at the anterior or posterior pole of the lens.
A diffuse large B-cell lymphoma arising from the central nervous system.
Autonomic disorder involving unilateral hyperhydrosis and flushing of the head and neck.
An angiosarcoma that arises from the heart. It most often arises in the right atrium near the atrioventricular groove. The prognosis is poor.
A rare variant of gallbladder adenocarcinoma. It is characterized by the presence of a malignant glandular epithelial infiltrate that resembles hepatocellular carcinoma.
A fistula which connects the oral cavity and the pharyngeal area via the aspects of the soft palate.
A usually malignant pancreatic neuroendocrine tumor producing vasoactive intestinal peptide (VIP). It is associated with watery diarrhea, hypokalemia, and hypochlorhydria or achlorhydria. One third of cases are metastatic at the time of diagnosis.
A rare benign primary endocardial tumor characterized macroscopically by its small size and highly papillar pedunculated appearance. The tumor is characterized histologically as avascular and presents with a single layer of endothelium. It is usually asymptomatic, however, cardiac or neurological symptoms due to ischemia or thromboembolic complications (such as syncope, transient ischemia, myocardial infarction or stroke) may be observed. The cardiac valves especially the aortic valve are commonly affected.
A variant of squamous cell carcinoma that arises from the larynx. It is characterized by an exophytic and papillary growth usually in the supraglottic area. The prognosis is favorable.
Partial displacement of the lens in the inferior direction.
Partial dislocation of the lens in a superior direction.
An accumulation of blood located between the retinal pigment epithelium (RPE) and Bruch's membrane.
A neoplastic process that affects the glandular epithelial cells of the cervix. There is no evidence of invasion. It is classified as low or high grade.
Rare involvement of the central nervous system by histiocytic sarcoma.
A Hodgkin lymphoma that arises from the central nervous system.
A circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point that is composed of localized hyperkeratosis (the latter may be demonstrated histopathologically).
A defect of the chest wall characterized by a depression of the sternum, giving the chest (""pectus"") a caved-in (""excavatum"") appearance.
Lack of paramedian peaks and median notch of the upper lip vermilion.
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
Height of the vermilion of the medial part of the lower lip more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the lower lip in the frontal view (subjective).
An electrocardiographic finding of an organized, regular atrial rhythm with atrial rate between 101 and 240 beats per minute. The P wave morphology must be distinct from the sinus P wave morphology. (CDISC)
A quantitative measurement of the amount of retrograde blood flow across the orifice of the mitral valve expressed as a percentage of the anterograde flow.
A quantitative measurement of the amount of retrograde blood flow across the orifice of the mitral valve.
A quantitative measurement of the amount of retrograde blood flow across the orifice of the aortic valve expressed as a percentage of the anterograde flow.
A quantitative measurement of the amount of retrograde blood flow across the orifice of the aortic valve.
An anomalous configuration of blood vessels that shunts arterial blood directly into veins without passing through the capillaries and that is located in the colon.
A condition in which a person has reduced protein production from one of the four alpha-globin alleles.
Adrenocorticotropic hormone independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing syndrome with characteristics of nodular enlargement of both adrenal glands that produce excess cortisol. The disease presents a bimodal age distribution with a rare subset presenting in the first years of life, particularly associated to McCune-Albright syndrome. Most patients present in their fifth or sixth decade. The adrenal glands can be massively enlarged bilaterally with the presence of numerous macronodules; however diffuse adrenal enlargement without nodules has been described. AIMAH is most often reported as sporadic but there are increasing reports of familial cases with autosomal dominant transmission.
Perinatal nerve injury involving the BRACHIAL PLEXUS involving a weak or paralyzed upper extremity.
Narrowing of the lumen of the right or left pulmonary artery branch.
Percent luminal narrowing of the left main coronary artery, at the point of maximal stenosis of the left main coronary artery.
A hemangioma that arises from the mediastinum. It can be of the capillary or the cavernous type.
A condition caused by long-lasting and ongoing infection with the spirochete Borrelia burgdorferi resulting in progressive inflammatory neurologic, neuromuscular, and dermatologic manifestations including ENCEPHALITIS; MYELITIS; acrodermatitis chronica atrophicans; and ARTHRITIS.
A non-metastasizing neoplasm that arises from the ovary characterized by the presence of glands or cysts lined by benign endometrial-type cells. It includes endometrioid adenofibroma, endometrioid cystadenofibroma, and endometrioid cystadenoma.
Right ventricular dysfunction (global or regional) with functional and morphological right ventricular abnormalities, with or without left ventricular disease.
An atrial septal defect characterized by a deficiency in the tissue separating the coronary sinus from the left atrium (LA). This results in partial or complete unroofing of the coronary sinus leading to a predominantly left-to-right shunt through the coronary sinus (LA to coronary sinus to right atrium [RA]). The orifice of the ostium is frequently large because of the increased flow. From the RA side, the defect is located at the level of the coronary sinus ostium and may also include some deficiency in atrial tissue around the ostium. From the LA side, the size can be variable depending on the degree of unroofing of the coronary sinus.
Thrombocytopenia caused by ingested or injected drugs. It may be the result of decreased platelet production due to bone marrow suppression or increased rate of platelet destruction.
Stenosis of the pulmonary artery that occurs above the valve.
Failure to respond to two or more trials of antidepressant monotherapy or failure to respond to four or more trials of different antidepressant therapies. (Campbell's Psychiatric Dictionary, 9th ed.)
A mature teratoma that arises from the pancreas.
A non-invasive mucinous cystic neoplasm that arises from the pancreas and is characterized by the presence of moderate dysplasia. The neoplastic columnar mucin-producing epithelial cells form papillary projections or crypt-like invaginations. There is cellular pseudostratification and mitotic activity present.
A carcinoma that arises from the pancreas showing a mixture of acinar and neuroendocrine malignant cells.
An esophageal carcinoma characterized by the presence of distinguishable squamous and glandular carcinomatous components.
A usually aggressive malignant epithelial neoplasm that arises from the anal canal. It is composed of malignant cells which do not display evidence of glandular or squamous differentiation.
A rare carcinoma that arises from the liver. The diagnosis is made by immunohistochemical studies. Morphologic studies alone cannot establish the diagnosis of carcinoma or further subclassify the malignant tumor.
A low-grade malignant blood vessel neoplasm that arises from the liver. It is characterized by the presence of epithelioid endothelial cells. The neoplastic cells are arranged in cords and nests, which are embedded in a myxoid to hyalinized stroma. Patients may be asymptomatic or present with an abdominal mass, ascites, and jaundice.
A mucinous cystic neoplasm that arises from the intrahepatic bile ducts and it is associated with an invasive carcinomatous component.
A Kaposi sarcoma that arises from the liver.
An adenoma that arises from the extrahepatic bile ducts. It is characterized by the presence of tubular and papillary growth patterns.
An adenocarcinoma that arises from the extrahepatic bile ducts. It is characterized by the presence of neoplastic tubular glands lined by columnar cells or neoplastic glands lined by goblet cells.
A malignant mesenchymal tumor with skeletal muscle differentiation, arising from the extrahepatic bile ducts.
A Kaposi sarcoma that arises from the extrahepatic bile ducts.
Drugs used in the treatment of urogenital conditions and diseases such as URINARY INCONTINENCE; PROSTATIC HYPERPLASIA; and ERECTILE DYSFUNCTION.
The lesion considered to be responsible for the acute coronary syndrome. (ACC)
Aortic dilatation refers to a dimension that is greater than the 95th percentile for the normal person age, sex and body size. In contrast, an aneurysm is defined as a localized dilation of the aorta that is more than 150 percent of predicted (ratio of observed to expected diameter 1.5 or more). Aneurysm should be distinguished from ectasia, which represents a diffuse dilation of the aorta less than 50 percent of normal aorta diameter.
A carcinoma arising from the ovary. It is characterized by the presence of malignant epithelial cells with clear cytoplasm in a fibrotic stroma.
An acute viral respiratory infection caused by a strain of influenza virus which is endemic in swine (pigs). Rarely reported in humans prior to 2009, the disease is caused by a mutated strain of swine influenza A (H1N1) virus. It is highly contagious and spreads mainly through coughing and sneezing. Signs and symptoms include fever, chills, coughing, sore throat headache, muscle ache, and generalized weakness. Antiviral medications are most effective in the first two days of the illness.
A condition in which the placental edge is within 2 cm of but not covering the cervical os.
A neoplasm that arises from the posterior cranial fossa. Examples include meningiomas and medulloblastomas.
A rare autoimmune disorder in which patients present with overlapping symptoms of systemic scleroderma and polymyositis or dermatomyositis.
Diminished production of adrenocortical hormones due to autoimmune destruction of the adrenal glands.
An electrocardiographic finding of episodic supraventricular tachycardia with abrupt onset and termination.
An electrocardiographic finding of abnormally slow heart rate with its origin in the sinus node. Thresholds for different age, gender, and patient populations exist. (CDISC)
Heart rate of greater than 100 beats per minute.
Chronic loss of joint motion of the interphalangeal joint of the thumb due to structural changes in non-bony tissue. This joint is also called Articulatio interphalangealis pollicis.
Chronic loss of joint motion of the metacarpophalangeal joint of the thumb due to structural changes in non-bony tissue. This joint is also called Articulatio metacarpophalangealis pollicis.
An inflammatory cellular deposit deposited on the corneal endothelium and visible as spots on the cornea.
A squamous cell lung carcinoma characterized by the presence of keratinization, pearl formation, and/or intercellular bridges.
A squamous cell carcinoma that arises from the vulva and is characterized by the presence of keratin pearls.
A disease where there is cellular death (necrosis) of bone components due to interruption of the blood supply.
A rare, highly aggressive carcinoma that arises from the salivary gland, predominantly the parotid gland. It is characterized by the presence of large pleomorphic malignant cells with abundant cytoplasm. Patients usually present with a rapidly growing mass.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the anal canal. It is characterized by the presence of malignant large cells.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the appendix. It is characterized by the presence of malignant large cells.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the extrahepatic bile ducts. It is characterized by the presence of malignant large cells.
Polydactyly of the foot most commonly refers to the presence of six toes on one foot. Postaxial polydactyly affects the lateral ray and the duplication may range from a well-formed articulated digit to a rudimentary digit.
Duplication of all or part of the first ray.
Precocious puberty for which no underlying cause can be identified.
Incoherent, disorganized or illogical thought processes.
An incision that involves deep soft tissues.
An incision that involves only the skin or subcutaneous tissue.
A congenital anomaly characterized by the presence of supernumerary fingers or toes.
Divergence of digits along the anteroposterior axis (in the plane of the sole).
Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as ""bony"" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as ""symphalangism"".
Absence of sex glands (gonads are the organs that produce gametes; testis in males and ovary in females). []
An acute and self-limited inflammatory disease of the large intestine (colon, cecum and rectum).
An increase in voltage of the PR segment below baseline. []
An electrocardiographic finding of PR segment depression below the iso-electric line in multiple precordial and/or limb leads. (CDISC)
A solid, raised, plateau-like (flat-topped) lesion greater than 1 cm in diameter and that has a yellow color.
Frequent, loose, and watery stools are noted in most infants, even if they are fed formula, until they are six to eight weeks old; after that, the stools become firmer and less frequent.
possessing both homosexual and heterosexual preferences; or true hermaphroditism, having gonads of both sexes.
The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls. [HPO:probinson]
An indication that an individual is living in an assisted living facility.
Lack of response to scratching of the skin of the medial thigh, which inmales normally elicits a brisk, short eveletion of the ipsilateral testis, a phenomenon that is referred to as the cremaster reflex. [PMID:12891505]
While performing an assessment of the eyes, the examiner notes whether the pupils are equal and round, reactive to light, and have the ability to accommodate. If all findings are normal, the abbreviation PERRLA is noted in the examiner's account of the physical examination.
A malignant neoplasm derived from the transitional epithelium of the urinary tract (urinary bladder, ureter, urethra, or renal pelvis). It is frequently papillary.
A measurement of the skull diameter, measured from the external occipital protuberance to the most prominent point of the frontal bone in the midline.
A loss of the ability to move the vocal fold on both sides.
A type of skin nodule (a lesions that is greater than either 10mm in both width and depth, and most frequently centered in the dermis or subcutaneous fat) with a yellowish coloration (that reflects a high lipid content of the lesion).
A rare leiomyosarcoma that arises from the appendiceal wall.
An aggressive malignant smooth muscle neoplasm, arising from the vulva. It is characterized by a proliferation of neoplastic spindle cells.
Increased susceptibility to streptococcus pneumoniae infections as manifested by a history of recurrent infections by streptococcus pneumoniae.
An increased susceptibility to bronchopulmonary infections as manifested by a history of recurrent bronchopulmonary infections.
Involuntary sudden, rapid, recurrent, nonrhythmic, stereotyped motor movement or vocalization.
Decreased retinal arteriolar diameters, which may decrease blood flow and slow oxygen delivery to regions of the retina.
A rare malignant adipose tissue neoplasm of the vulva.
A rare diffuse large B-cell lymphoma that arises from the liver and the bulk of the tumor is located in the liver.
Raised, well-circumscribed areas of erythema and edema involving the dermis and epidermis. Urticaria is intensely pruritic, and blanches completely with pressure.
An elevation of the eyelid above the normal level in the primary position. [PMID:7735674]
An aggressive malignant smooth muscle neoplasm, arising from the retroperitoneum. It is characterized by a proliferation of neoplastic spindle cells.
An esophageal carcinoma characterized by the absence of microscopic features of squamous differentiation. However, there is immunohistochemical evidence of squamous differentiation.
An undifferentiated carcinoma that arises from the larynx. This category includes lymphoepithelial carcinoma and giant cell carcinoma.
An aggressive high grade sarcoma that arises from the ovary. It is characterized by the presence of marked pleomorphism and nuclear atypia in the neoplastic mesenchymal cells. The prognosis is poor.
A term that refers to a heterogeneous group of uncommon soft tissue sarcomas that do not show an identifiable line of differentiation using currently available technologies. This is a diagnosis of exclusion and includes undifferentiated pleomorphic sarcoma (also known as malignant fibrous histiocytoma), undifferentiated spindle cell sarcoma, undifferentiated round cell sarcoma, and undifferentiated epithelioid sarcoma.
Hypospadias with location of the urethral meatus in the scrotum.
A question about an individual's difficulty dressing themselves without help.
Bleeding that is disproportionate to the offending trauma.
An apocrine adenocarcinoma that arises from the sweat glands in the vulva.
An eccrine adenocarcinoma that arises from the sweat glands in the vulva.
Little or no appetite for breakfast due to eating more food after dinner than during the meal and eating more than half of daily food intake after dinner hour.
An aggressive variant of squamous cell carcinoma that arises from the floor of the mouth. It is characterized by the presence of small malignant cells with hyperchromatic nuclei and scant amount of cytoplasm forming lobules with peripheral palisading.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the appendix. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the anal canal. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
A rare primary malignant hepatic neoplasm of childhood that is mesenchymal in origin. It can rarely occur in adults. It has manifestations of abdominal mass, right upper quadrant or epigastric pain, nausea, anorexia, intermittent fever or headache.
A malignant soft tissue neoplasm that arises from the extrahepatic bile ducts. Representative examples include Kaposi sarcoma, leiomyosarcoma, and rhabdomyosarcoma.
EEG with sharp waves in the frontal region, i.e., sharp transient waves of a duration between 80 and 200 msec.
EEG with sharp waves in the temporal region, i.e., sharp transient waves of a duration between 80 and 200 msec.
EEG with sharp waves in the parietal region, i.e., sharp transient waves of a duration between 80 and 200 msec.
EEG with sharp waves in the occipital region, i.e., sharp transient waves of a duration between 80 and 200 msec.
EEG with generalized sharp transient waves of a duration less than 80 msec.
EEG with sharp waves in the central region, i.e., sharp transient waves of a duration between 80 and 200 msec.
Thymic neuroendocrine carcinoma is a type of thymic epithelial neoplasm displaying evidence of neuroendocrine differentiation. The exact prevalence or incidence is unknown. Men are predominantly affected. Thymic neuroendocrine carcinoma is aggressive with a poor prognosis.
A squamous cell carcinoma that arises from the vulva and is characterized by the presence of nests of malignant basaloid cells with a scant amount of cytoplasm.
A carcinoma that arises from the ovary and is characterized by the presence of small malignant cells. It includes small cell carcinoma, hypercalcemic type and small cell carcinoma, pulmonary type.
A steroid tumor of the ovary which has an aggressive clinical course and metastasizes to other anatomic sites. It is usually of large size and is characterized by nuclear atypia, increased mitotic activity, hemorrhage, and necrosis. Sometimes, patients have abdominal metastases at presentation.
A malignant neoplasm of the ovary with an invasive epithelial component and a fibrotic stroma. The epithelial component is characterized by the presence of malignant epithelial cells of serous type, forming glandular, papillary, and solid patterns.
A malignant neoplasm of the ovary with an invasive epithelial component and a fibrotic stroma. The epithelial component is characterized by the presence of malignant epithelial cells with intracytoplasmic mucin. Cystic spaces are also present which contain mucoid material.
An endometrioid adenocarcinoma that arises from the ovary and exhibits squamous differentiation. The squamous cell component often has a cytologically benign appearance.
A benign neoplasm of the ovary characterized by the presence of glandular structures with endometrial-type well-differentiated cells in a fibrotic stroma.
An extremely rare penile epithelial neoplasm, histologically composed of nests of epithelial cells floating in lakes of extracellular, PAS-positive mucin, with clinical characteristics of a nonhealing ulcer or soft mass in the preputium or glans area, with itching and burning often preceding appearance of the lesion. Lymphadenopathy may indicate dissemination. Mucinous metaplasia of the penis may be a risk factor.
A very rare small cell carcinoma that arises from the kidney. The prognosis is poor.
Involvement of the meninges by Hodgkin or non-Hodgkin lymphoma.
A non-Hodgkin lymphoma that arises from the central nervous system.
An electrocardiographic finding of complete failure of atrial electrical impulse conduction to the ventricles. This is manifested on the ECG by disassociation of atrial and ventricular rhythms. The atrial rate must be faster than the ventricular rate. (CDISC)
An electrocardiographic finding of a wide QRS complex with evidence of delayed conduction to the right ventricle, manifested by a widened initial portion of the QRS in V1 and V2, a widened S wave in V5, V6, I and aVL, and with QRS duration less than 120 ms. (CDISC)
An electrocardiographic finding of a slightly widened QRS duration (typically less than 120 ms) with leftward frontal plane QRS axis and typically small Q waves in leads I and aVL. (CDISC)
An electrocardiographic finding of an S1Q3 pattern and QRS axis greater than or equal to 120 degrees. It is usually seen in association with other abnormalities (e.g. RBBB or RVH). (CDISC)
Pallor of the perifoveal macula of the retina with appearance of a small circular reddish choroid shape as seen through the fovea centralis due to relative transparancy of the macula.
Stage I includes: IA: T1, N0, M0 and IB: (T0, N1mi, M0); (T1, N1mi, M0). T1: Tumor 20 mm or less in greatest dimension. T1 includes T1mi. T1mi: Tumor 1 mm or less in greatest dimension. T0: No evidence of primary tumor. N0: No regional lymph node metastasis. N1mi: Nodal micrometastases. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 7th Ed.)
Stage IIIC Breast Cancer was added in the 6th Edition AJCC Staging Manual, on the basis of metastasis to the infraclavicular lymph nodes (N3) plus any T, M0.
Stage IIA includes: T3, N0, M0. T3: Tumor invades through the muscularis propria into pericolorectal tissues. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: T4a, N0, M0. T4a: Tumor penetrates to the surface of the visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: (T1-T2, N1/N1c, M0); (T1, N2a, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. N1: Metastasis in 1-3 regional lymph nodes. N1c: Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional lymph node metastasis. N2a: Metastasis in 4-6 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: (T3-T4a, N1/N1c, M0); (T2-T3, N2a, M0); (T1-T2, N2b, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor penetrates to the surface of the visceral peritoneum. N1: Metastasis in 1-3 regional lymph nodes. N1c: Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional lymph node metastasis. N2a: Metastasis in 4-6 regional lymph nodes. N2b: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIC includes: (T4a, N2a, M0); (T3-T4a, N2b, M0); (T4b, N1-N2, M0). T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor penetrates to the surface of the visceral peritoneum. T4b: Tumor directly invades or is adherent to other organs or structures. N1: Metastasis in 1-3 regional lymph nodes. N2: Metastasis in four or more regional lymph nodes. N2a: Metastasis in 4-6 regional lymph nodes. N2b: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: IVA: (Any T, Any N, M1a); IVB: (Any T, Any N, M1b). M1a: Metastasis confined to one organ or site (e.g., liver, lung, ovary, nonregional node). M1b: Metastases in more than one organ/site or the peritoneum. (AJCC 7th ed.)
Stage 0 includes: (Tis, N0, M0); (Ta, N0, M0). Tis: Carcinoma in situ. Ta: Non-invasive verrucous carcinoma. cN0: No palpable or visibly enlarged inguinal lymph nodes. pN0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T1/T2, N3, M0); (T3, Any N, M0). T1: Invasive vulvar cancer confined to the vulva or perineum. T2: Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement). T3: Vulvar cancer with tumor of any size with extension to any of the following: upper/proximal 2/3 urethra, upper/proximal 2/3 vagina, bladder mucosa, rectal mucosa, or fixed to pelvic bone. N3: Vulvar cancer with fixed or ulcerated regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IA includes: T1a, N0, M0. T1a: For leiomyosarcoma and endometrial stromal sarcoma: tumor 5 cm or less in greatest dimension. For adenosarcoma: tumor limited to endometrium/endocervix. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IB includes: T1b, N0, M0. T1b: For leiomyosarcoma and endometrial stromal sarcoma: tumor more than 5 cm in greatest dimension. For adenosarcoma: tumor invades to less than half of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IC includes: T1c, N0, M0. T1c: For adenosarcoma: tumor invades more than half of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. Stage IC does not apply for leiomyosarcoma and endometrial stromal sarcoma. (AJCC 7th ed.)
Stage IIIA includes: T3a, N0, M0. T3a: Tumor infiltrates abdominal tissues, one side. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Tumor infiltrates abdominal tissues, more than one side. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
Stage IVA includes: T4, Any N, M0. T4: Tumor involves bladder or rectum. M0: No distant metastasis. This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distal metastasis (excluding adnexa, pelvic and abdominal tissues). This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
Absence of menses for an interval of time equivalent to a total of more than (or equal to) 3 previous cycles or 6 months.
Particularly loud snoring, snoring at high volume. [NCIT:C121601]
Behavior that is not in line with social norms.
A compound containing elemental iron as the sodium salt of a ferric ion carbohydrate complex in an alkaline aqueous solution with approximately 20% sucrose w/v in water for injection, used to replete the total body content of iron. Iron is critical for normal hemoglobin and myoglobin syntheses to maintain oxygen transport and various enzymatic processes, including the biosynthesis of deoxyribonucleotides catalyzed by ribonucleotide reductase (RNR).
The presence of hypertrophy of the breast.
Abnormally increased dimension of the maxilla, especially relative to the mandible, resulting in a malocclusion or malalignment between the upper and lower teeth or in anterior positioning of the nasal base, increased convexity of the face, increased nasolabial angle, or increased width (transverse dimension of the maxilla. []
Reduced strength of the muscles that lift or otherwise move the foot at the ankle.
A ring-shaped skin finding with clear central area.
A macule (flat, distinct, discolored area of skin less than 1 cm wide that does not involve any change in the thickness or texture of the skin) with a red or reddish color often associated with inflammation or irritation.
A mild delay in the achievement of motor or mental milestones in the domains of development of a child.
A lack of strength in the triceps muscle, which normally is responsible for extending (straightening) the elbow and mediating certain shoulder movements.
Human BRUCELLA infection with pulmonary involvement such as EMPYEMA; LUNG ABSCESS; and PLEURAL EFFUSION.
The numerical sum between zero and ten that is computed from individual values of zero to two that are assigned to five different areas of interest in newborn screenings at fifteen minutes after birth. These areas are breathing, muscle tone, pulse rate, reflex irritability and skin color.
The numerical sum between zero and ten that is computed from individual values of zero to two that are assigned to five different areas of interest in newborn screenings at twenty minutes after birth. These areas are breathing, muscle tone, pulse rate, reflex irritability and skin color.
Abnormally lax eyelid associated with tissue relaxation; it can be demonstrated by the eyelid distraction test and/or the eyelid snap test. [UManchester:psergouniotis]
A moderate delay in the achievement of motor or mental milestones in the domains of development of a child.
A form of RETINAL DEGENERATION in which abnormal CHOROIDAL NEOVASCULARIZATION occurs under the RETINA and MACULA LUTEA, causing bleeding and leaking of fluid. This leads to bulging and or lifting of the macula and the distortion or destruction of central vision.
A description of an individual's current and past use and/or abuse of drugs and chemicals. This includes prescription medication, illicit drugs and recreational substances.
Hepatocellular carcinoma is the major histologic type of malignant primary liver neoplasm. It is the fifth most common cancer and the third most common cause of death from cancer worldwide. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Hepatoblastomas comprise 1 to 2% of all malignant neoplasms of childhood, most often occurring in children under 3 years of age. Hepatoblastomas are thought to be derived from undifferentiated hepatocytes (Taniguchi et al., 2002).
A rare, high grade sarcoma that arises from the endometrial stroma or myometrium without a specific type of differentiation. It was previously also known as high grade endometrial stromal sarcoma. In 2014, high grade endometrial stromal sarcoma was reclassified and is currently considered a distinct and rare neoplasm. Undifferentiated uterine sarcoma has a worse prognosis.
Abnormal outpouching or sac-like dilatation of one of the anatomic dilations of the ascending aorta, which occurs just above the aortic valve.
Vaccines or candidate vaccines containing inactivated hepatitis B or some of its component antigens and designed to prevent hepatitis B. Some vaccines may be recombinantly produced.
A recombinant peptide that is chemically identical to or similar to the endogenous thrombin. Thrombin, a serine protease, plays significant roles in the coagulation cascade, such as breaking down soluble fibrinogen to promote fibrin clot formation, as well as activating factor XI, factor V, and factor VIII.
An acute or chronic infectious process affecting the bones.
An anatomical variant of the cervical atlas in which osseous bridges connect posterior superior articular process to the posterior arch thereby covering grooves for the VERTEBRAL ARTERY.
A very rare condition characterised by glomerular accumulation of microtubules in the mesangium and the glomerular basement membrane, that mainly presents with proteinuria, micro-haematuria, nephrotic syndrome, renal insufficiency and haematologic malignancy. Aetiopathology is unknown. It may arise spontaneously or be associated with lymphoproliferative disorders, hepatitis C virus infection, leucocytoclastic vasculitis and hypocomplementaemia.
Detection of odors that are not present.
Deposition of calcium in normally non calcified tissue
A kind of focal dystonia characterized by forceful contractions of the face, jaw, and/or tongue causing difficulty in opening and closing the mouth and often affecting chewing and speech.
Involuntary protrusions, movements, spams and contortions of the tongue.
A condition in which a person is unable to tell which side of the body has been touched.
A disorder of the heart and kidneys in which dysfunction of one of the organs induces dysfunction of the other organ.
Abnormally high levels of alanine transaminase (ALT) and/or aspartate transaminase (AST) in the blood.
Pathological elevation of intra-abdominal pressure (>12 mm Hg). It may develop as a result of SEPSIS; PANCREATITIS; capillary leaks, burns, or surgery. When the pressure is higher than 20 mm Hg, often with end-organ dysfunction, it is referred to as abdominal compartment syndrome.
Hemolytic anemia, in which patients are heterozygous for both the sickle cell gene and a thalassemia gene.
A form of retention cyst of the floor of the mouth, usually due to obstruction of the ducts of the submaxillary or sublingual glands, presenting a slowly enlarging painless deep burrowing mucocele of one side of the mouth. It is also called sublingual cyst and sublingual ptyalocele.
A localized mast cell neoplasm without metastatic potential.
A sensation as of repetitive pin pricks, caused by cold or by striking a nerve, or as a result of various diseases of the central or peripheral nervous system.
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
A rare adenocarcinoma of the major and minor salivary glands, originating from basaloid, myoepithelial and ductal cells. While morphologically resembling basal cell carcinomas, it is a distinct entity. The tumor is not encapsulated, may invade locally, and less frequently may metastasize. It usually occurs in older patients.
Gastritis that is characterized by erosion of the mucosal surface.
Transport of substances across a biological membrane from an area of higher concentration to an area of lower concentration by means of a carrier molecule.
The chemical reactions and pathways resulting in the formation of isoquinoline alkaloids, alkaloid compounds that contain bicyclic N-containing aromatic rings and are derived from a 3,4-dihydroxytyramine (dopamine) precursor that undergoes a Schiff base addition with aldehydes of different origin. [GOC:mah, http://www.life.uiuc.edu/ib/425/lecture32.html]
The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell, followed by propagation of the signal via beta-catenin, and ending with a change in transcription of target genes. In this pathway, the activated receptor signals via downstream effectors that result in the inhibition of beta-catenin phosphorylation, thereby preventing degradation of beta-catenin. Stabilized beta-catenin can then accumulate and travel to the nucleus to trigger changes in transcription of target genes. [GOC:bf, GOC:dph, PMID:11532397, PMID:19619488]
Hypertrophy (increase in size) of muscle cells (as opposed to hyperplasia, which refers to an increase in the number of muscle cells).
The numerical value that represents a clinical assessment of neurological and physical criteria, performed between birth and five days of age, to determine an infant's gestational age and maturity.
Nontender, round and firm, but slightly compressible, intradermal or subcutaneous cyst measuring 0.5-5 cm in diameter. Trichilemmal cysts are acquired rather than congenital, and tend to appear on the scalp rather than the face, and to be intradermal rather than subcutaneous.
Compounds consisting of a short peptide chain conjugated with an acyl chain.
Compounds that specifically inhibit PHOSPHODIESTERASE 3.
A disorder characterized by recurrent episodes of binge-eating over which the individual feels a lack of control; these episodes of binge-eating are followed by recurrent compensatory behavior to prevent weight gain, usually self-induced vomiting. In addition, self-evaluation is unduly influenced by body image.
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Infections of the genital tract in females or males. They can be caused by endogenous, iatrogenic, or sexually transmitted organisms.
An autosomal dominant hereditary neoplastic syndrome characterized by the presence of multiple melanocytic nevi, some of which are atypical, and a family history of melanoma. Patients are at an increased risk of developing melanoma and pancreatic cancer.
Intraepidermal squamous cell carcinoma, confined to the epidermis. There is no evidence of invasion.
Ischemic necrosis of the spinal cord caused by occlusion of the arteries that supply blood to the spinal cord. Signs and symptoms include intermittent back pain, pain in the legs, paralysis, and incontinence.
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. [HPO:probinson]
An abnormality of one or more of the set of bones that make up the facial skeleton.
Any of the recombinant form of the naturally occurring Interleukin-1 Receptor Antagonist that blocks the biological activity of Interleukin-1 by binding to the Interleukin-1 receptor.
An abnormal breathing pattern originating from lower brainstem neurons and characterized by labored breaths, gasping, and, often, myoclonus and grunting.
A local or systemic infection associated with the use of a peritoneal dialysis catheter.
Cystic, urine-containing intrarenal cavities lined with transitional cell epithelium that communicate through a narrow channel with the collecting system.
Invagination of the superior part of the auricle under a fold of temporal skin.
The dimeglumine salt form of fosaprepitant, the water-soluble, N-phosphorylated prodrug of aprepitant, with antiemetic activity. Upon intravenous administration and rapid conversion to aprepitant, this agent binds selectively to the human substance P/neurokinin 1 (NK1) receptors in the central nervous system (CNS). This inhibits receptor binding of the endogenous substance P and prevents substance P-induced emesis.
The presence of live pathogens in the blood causing significant clinical consequences such as fever, chills, or hypotension.
A small molecule inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential chemosensitizing, radiosensitizing, and antineoplastic activities. Olaparib selectively binds to and inhibits PARP, inhibiting PARP-mediated repair of single strand DNA breaks; PARP inhibition may enhance the cytotoxicity of DNA-damaging agents and may reverse tumor cell chemoresistance and radioresistance. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins and can be activated by single-stranded DNA breaks.
An intermittent and self-limiting headache disorder in individuals with CEREBROSPINAL FLUID SHUNTS emplaced for the treatment of HYDROCEPHALUS. The symptoms of headache, vomiting, and cranial neuropathies are associated with intermittent obstruction of the shunt.
A group of autoinflammatory syndromes caused by mutations in the NLRP3 gene. Signs and symptoms include rash, fever, headache, joint pain, conjunctivitis, and weakness. The symptoms may exacerbate with exposure to cold weather.
A recombinant form of human antithrombin with anticoagulant activity. Antithrombin alfa blocks thrombin activity and thus thrombus formation. It is used in patients with antithrombin deficiency.
A type of chronic kidney disease with normal or increased glomerular filtration rate (GFR at least 90 mL/min/1.73 m2).
The red blood cells from a unit of whole blood following removal of most of the plasma, leaving a unit with a hematocrit of about 60%.
The hydrobromide salt of an aminoketone with antidepressant activity. The molecular mechanism of the antidepressant effect of bupropion is unknown. This agent does not inhibit monoamine oxidase and, compared to classical tricyclic antidepressants, is a weak blocker of the neuronal uptake of serotonin and norepinephrine. Buproprion also weakly inhibits the neuronal re-uptake of dopamine.
A type of chronic kidney disease with mildly reduced glomerular filtration rate (GFR 60-89 mL/min/1.73 m2).
A type of chronic kidney disease with moderately reduced glomerular filtration rate (GFR 30-59 mL/min/1.73 m2).
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Excessive blood loss within the second trimester but prior to onset of labor.
Dilation of fetal KIDNEY PELVIS. It is a common PRENATAL ULTRASONOGRAPHY finding with no significant long-term sequelae.
A type of chronic kidney disease with severely reduced glomerular filtration rate (GFR 15-29 mL/min/1.73 m2).
History of a first-degree relative (less than 55 years for male relatives or less than 65 years for female relatives) having had any of the following: coronary artery disease, myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or sudden cardiac death without obvious cause.
The presence of an infectious agent in the blood circulation. []
A pharmaceutical preparation of amlodipine besylate and olmesartan medoxomil that combines ANGIOTENSIN II TYPE I RECEPTOR ANTAGONIST and CALCIUM CHANNEL BLOCKER activities. It is used in the management of HYPERTENSION.
An orally available mesylate salt form of the etexilate prodrug of dabigatran, a benzimidazole and direct thrombin inhibitor with anticoagulant activity. Upon administration, dabigatran etexilate is hydrolyzed by esterases and is converted into dabigatran. Dabigatran reversibly binds to and inhibits the activity of thrombin, a serine protease that converts fibrinogen into fibrin. This disrupts the coagulation cascade and inhibits the formation of blood clots.
A competitive muscarinic receptor antagonist with muscle relaxant and urinary antispasmodic properties. Fesoterodine is rapidly hydrolyzed in vivo into its active metabolite 5-hydroxy methyl tolterodine, which binds and inhibits muscarinic receptors on the bladder detrusor muscle, thereby preventing bladder contractions or spasms caused by acetylcholine. This results in the relaxation of bladder smooth muscle and greater bladder capacity, in addition to a reduction in involuntary muscle contractions and involuntary loss of urine. The active metabolite does not interact with alpha-adrenergic, serotonergic, histaminergic and excitatory amino acid receptors and is eliminated via renal excretion.
The fumarate salt form of fesoterodine, a competitive muscarinic receptor antagonist with muscle relaxant and urinary antispasmodic properties. Fesoterodine is rapidly hydrolyzed in vivo into its active metabolite 5-hydroxy methyl tolterodine, which binds and inhibits muscarinic receptors on the bladder detrusor muscle, thereby preventing bladder contractions or spasms caused by acetylcholine. This results in the relaxation of bladder smooth muscle and greater bladder capacity, in addition to a reduction in involuntary muscle contractions and involuntary loss of urine. The active metabolite does not interact with alpha-adrenergic, serotonergic, histaminergic and excitatory amino acid receptors and is eliminated via renal excretion.
The bromide salt form of methylnaltrexone, a methyl derivative of noroxymorphone with selective, peripherally-acting mu-opioid receptor antagonistic activity. Methylnaltrexone displaces opioids from peripheral opioid receptors in the gastrointestinal tract, the bladder, and the skin, thereby reversing the opioid-related peripheral side-effects, such as constipation, urinary retention, and pruritis, respectively. Unlike naltrexone and due to the presence of a positively charged nitrogen atom in methylnaltrexone, this agent does not cross the blood-brain barrier and does not affect the centrally-mediated analgesic effect of opioids.
An oral small molecule inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (InsR) tyrosine kinases with potential antineoplastic activity. Dual IGF-IR/InsR inhibitor BMS-754807 binds reversibly to and inhibits the activities of IGF-1R and InsR, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-1R and InsR tyrosine kinases, overexpressed in a variety of human cancers, play significant roles in mitogenesis, angiogenesis, and tumor cell survival.
A recombinant protein consisting of the cytokine interleukin-2 (IL-2) fused to a humanized soluble T-cell receptor (TCR) directed against a tumor suppressor p53-derived antigen with potential immunopotentiating and antineoplastic activities. The TCR moiety of IL-2 recombinant fusion protein ALT-801 binds to tumor cells displaying p53 epitope/MHC complexes; subsequently, the tumor cell-localized IL-2 moiety may stimulate natural killer (NK) cell and T cell cytotoxic immune responses against p53-expressing tumor cells.
Plasma cell myeloma with beta-2-microglobulin greater than or equal to 5.5 (median survival of 29 months). Note that the older Durie/Salmon staging system defines stage III quite differently. (PDQ)
Plasma cell myeloma with blood levels of beta-2-microglobulin between 3.5 and 5.5 mg/L.
Plasma cell myeloma with beta-2-microglobulin less than 3.5 and albumin greater than or equal to 3.5 (median survival of 62 months). Note that the older Durie/Salmon staging system defines stage I quite differently. (PDQ)
An electrocardiographic finding of blocked cardiac electrical impulse conduction along the fibers of the right bundle branch that cannot be attributed to any cause.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with tumor-derived clonal immunoglobulin (Ig) with potential immunostimulatory and antineoplastic activities. Upon administration, idiotype-pulsed autologous dendritic cell vaccine APC8020, containing idiotype (Id) protein structures that can be recognized by antibodies and by CD41 T lymphocytes and CD81 T lymphocytes, may stimulate antitumoral cytotoxic T lymphocyte (CTL) and antibody responses against Id-expressing tumor cells. The Id represents the unique antigenic determinants in the variable regions of the clonal Ig.
A synthetic saponin, chemically identical to the natural saponin QS-21, with immunoadjuvant activity. When co-administered with vaccine antigens, immunoadjuvant QS-DG may increase total antitumoral vaccine-specific antibody responses and cytotoxic T-lymphocyte (CTL) responses.
Problem associated with facility not providing satisfactory initial and/or periodic user training covering operation of a medical device.
A radioimmunoconjugate comprised of the recombinant humanized monoclonal antibody bevacizumab conjugated with the gamma-emitting radioisotope indium In 111. Indium I 111 bevacizumab binds to vascular endothelial growth factor (VEGF), allowing the detection of VEGF distribution using gamma scintigraphy.
The humanized monoclonal antibody huPAM4, directed against the pancreatic cancer antigen MUC-1 and labeled with the gamma-emitting radioisotope indium In 111, with radioisotopic and antibody activities. Upon administration, indium In 111 monoclonal antibody huPAM4 may bind to MUC-1-positive tumor cells, allowing radioimmunolocalization with gamma scintigraphy. Overexpressed by many tumor cell types, MUC-1 antigen, a mammary-type apomucin, is a high-molecular-weight transmembrane glycoprotein.
An electrocardiographic finding of a delay in impulse propagation through the atria. This is characterized by broad P waves which are often biphasic in V1. (CDISC)
An intranasal formulation of the synthetic cyclohexanone ketamine with analgesic and anesthetic activities. Although its mechanism of action is not well understood, ketamine appears to non-competitively block N-methyl-D-aspartate (NMDA) receptors and agonistically bind to and activate opioid mu and sigma receptors, thereby reducing pain perception, inducing sedation, and producing dissociative anesthesia.
Zinc ion requiring two electrons to return to its elemental state.
An electrocardiographic finding of a supraventricular rhythm where the ratio of impulses generated above the atrioventricular node to the number of impulses conducted through to the ventricles is 2:1. This is manifested on the ECG as 2 P waves per QRS complex. (CDISC)
A peptide vaccine consisting of multiple epitopes derived from the human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, with potential immunostimulating and antineoplastic activities. hTERT I540/R572Y/D988Y multipeptide vaccine contains strongly antigenic peptide epitopes I540 (9-mer), R572Y (9-mer) and D988Y (10-mer). Vaccination with this agent may elicit a cytotoxic T cell (CTL) response against telomerase-expressing tumor cells. Directly linked to tumorigenesis, telomerase is expressed in the majority of human cancer cells but is infrequently expressed in normal cells.
An immunoconjugate consisting of the anti-tumor cytokine interleukin-12 (IL-12) fused to the tumor-targeting antibody BC1 with potential immunostimulatory and antineoplastic activities. The antibody moiety of huBC1-huIL12 fusion protein AS1409 binds to the human fibronectin splice variant ED-B, delivering IL-12 directly to the tumor vasculature; tumor vasculature-targeted IL-12 initiates localized immune cascade responses and exhibits cytotoxic and anti-angiogenic activity while minimizing the systemic side effects of IL-12. The human fibronectin splice variant ED-B is over-expressed in the extracellular matrix and blood vessels of tumor tissues.
A fowlpox vaccine containing the tumor-associated antigen mucin-1 (MUC1), found in pancreatic tumor cells, and a TRIad of COstimulatory Molecules (B7-1, ICAM-1 and LFA-3; TRICOM), which is designed to enhance antigen presentation and activation of immune responses critical for tumor destruction. Vaccination with this agent may elicit a host immune response against MUC1-expressing tumor cells.
An iodine I-123 conjugate of metomidate (MTO) with potential application in adrenal imaging. Metomidate is a potent and selective inhibitor of the cytochrome P-450 enzymes, especially CYP11B1 (11 beta-hydroxylase) and CYP11B2 (aldosterone synthase). Because both CYP11B1 and CYP11B2 are expressed exclusively in the adrenal cortex, I-123 iodometomidate can be used as a radiotracer for adrenal scintigraphy.
A diagnostic radiopharmaceutical comprised of iodo-azomycin galactopyranoside (IAZGP) labeled with the positron-emitting radioisotope iodine I 124 and used as an imaging agent. Iodine I 124 iodo-azomycin galactopyranoside (I-124 IAZGP) is reduced under hypoxic conditions, covalently binding to macromolecules in hypoxic cells. After incorporation into hypoxic tumor cell DNA, I-124 IAZGP can be localized and quantified using positron emission tomography (PET), allowing a quantitative assessment of hypoxic tumor burden. IAZGP appears to have a higher water solubility and faster clearance from normal tissue than traditional imidazole tracers.
A radioimmunoconjugate consisting of a murine IgG2a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR) labeled with iodine I 125 with potential antineoplastic activity. Iodine I 125 anti-EGFR-425 monoclonal antibody binds specifically to the epidermal growth factor receptor (EGFR). Upon binding to EGFR-expressing tumor cells, this agent is internalized, selectively delivering a potentially cytotoxic dose of gamma radiation. EGFR is a receptor tyrosine kinase that may be overexpressed on the cell surfaces of various solid tumors.
A radioiodine-labeled cholesterol analogue with radioisotopic activity. Iodine 131-I-6-beta-iodomethyl-19-norcholesterol accumulates in tissues where steroid hormones are produced, including the adrenal cortex and, to a lesser extent, the ovaries and the testes. After binding to low-density lipoprotein (LDL) receptors in the adrenal cortex, this agent is internalized, permitting scintigraphic localization of areas of adrenocortical glucocorticoid, mineralocorticoid and androgen secretion, and the scintigraphic assessment of adrenocortical function.
An electrocardiographic finding of a significant elevation above the baseline of the J point. (CDISC)
A proprietary nutritional supplement with potential male sexual function enhancement effect. L-Arginine/American ginseng/Korean ginseng/Ginkgo biloba-based supplement incorporates a standardized combination of Ginkgo biloba (24% flavone glycosides, 6% terpene lactones), Korean ginseng (Panax ginseng -30% ginsenosides), American ginseng (Panax quinquefolius - 5% ginsenosides), L-Arginine, along with vitamins B6, B12, folate, thiamin, riboflavin, niacin, biotin, pantothenic acid, vitamins A, C, E, selenium, and zinc. L-Arginine is a precursor for nitric oxide (NO); ginseng may facilitate the conversion of L-Arginine into NO by NO synthase; the natural herb Ginkgo biloba may promote microvascular circulation. Overall, this supplement may increase NO production, which leads to vasodilatation and enhanced circulation. The improved blood flow is critical for sexual function and arousal.
A multipeptide vaccine consisting of peptides derived from lymphocyte antigen 6 complex locus K (LY6K) and type I and II vascular endothelial growth factor receptors (VEGFRs) with potential antineoplastic activity. Upon administration, LY6K/VEGFR1/VEGFR2 multipeptide vaccine may elicit an antitumor cytotoxic T-lymphocyte (CTL) immune response against LY6K-expressing tumor cells and/or VEGFR-expressing vascular endothelial cells involved in tumor angiogenesis. LY6K is a tumor-associated antigen (TAA) that occurs singly in glycosylphosphatidyl-inositol (GPI)-linked cell-surface glycoproteins or as three-fold repeated domain in the urokinase-type plasminogen activator receptor; VEGFRs are cell surface receptors that stimulate endothelial cell proliferation, invasion, angiogenesis, and vasculogenesis upon ligand binding and receptor activation.
Problem associated with user facility not receiving adequate service documentation, guidelines, or recommendations to perform preventative and corrective maintenance and performance assurance checks.
A proprietary dietary supplement. Lactobacillus fermented extract is made from soymilk fermented by several strains of lactobacillus and yeast via a symbiotic co-culturing technology. The composition of the agent includes amino acids, vitamins, minerals, fatty acids, isoflavones, and saponins. Lactobacillus fermented extract may support healthy intestinal function.
Often sleeping; play entirely limited to very passive activities.
Mostly in bed; participates in quiet activities.
Gets dressed, but lies around much of the day; no active play, able to participate in all quiet play and activities.
Up and around, but minimal active play; keeps busy with quieter activities.
Both greater restriction of and less time spent in play activity.
A liposomal formulation containing a fixed combination of the antineoplastic agents cytarabine and daunorubicin in a 5:1 molar ratio. Liposome-encapsulated daunorubicin-cytarabine has been designed to provide optimal delivery of a specific ratio of cytarabine to daunorubicin, one that has been shown to be synergistic in vitro. The antimetabolite cytarabine competes with cytidine for incorporation into DNA, inhibiting DNA synthesis. This agent also inhibits DNA polymerase, resulting in a decrease in DNA replication and repair. Daunorubicin, an intercalator and a topoisomerase II inhibitor, prevents DNA replication and inhibits protein synthesis. This agent also generates oxygen free radicals, resulting in the cytotoxic lipid peroxidation of cell membrane lipids.
A plasmid DNA encoding human manganese superoxide dismutase (MnSOD) and liposomally encapsulated with potential chemoprotective activity. When administered orally and localizing in the esophagus, MnSOD-plasmid liposomes express MnSOD, which scavenges reactive oxygen species (ROS); MnSOD scavenging of ROS may result in a reduction in ROS-mediated lipid peroxidation, apoptosis, and micro-ulceration in the epithelial lining of the esophagus.
A recombinant Listeria-based cancer vaccine containing a live-attenuated strain of the facultative intracellular bacterium Listeria monocytogenes (Lm) expressing human mesothelin with potential immunostimulatory and antineoplastic activities. Upon administration of this vaccine, Listeria invade professional phagocytes within the immune system and express mesothelin, which may activate a cytotoxic T-lymphocyte (CTL) response against mesothelin-expressing tumor cells, resulting in tumor cell lysis. In addition, the Listeria vector itself may induce a potent innate and adaptive immunity unrelated to mesothelin expression. Mesothelin is a cell surface glycoprotein involved in cell adhesion and is overexpressed in many epithelial-derived cancers, including pancreatic, ovarian and lung cancers, and malignant mesotheliomas.
A succinate salt form of abacavir, a nucleoside reverse transcriptase inhibitor analog of guanosine. This agent decreases HIV viral loads, retards or prevents the damage to the immune system, and reduces the risk of developing AIDS.
Aluminum ion requiring three electrons to return to its elemental state.
An inhibitor of inosine monophosphate dehydrogenase with activity against several influenza A and B viruses. Amitivir inhibits the conversion of inosine monophosphate to xanthosine monophosphate, the rate-limiting step in the de novo biosynthesis of guanine nucleotides, leading to inhibition of cell proliferation.
The hydrochloride salt form of amotosalen, a synthetic psoralen and light-activated DNA, RNA crosslinking agent, with protective activity against pathogens such as bacteria, viruses, protozoa, and leukocytes. Prior to administration amotosalen is added to plasma and platelets, then in vivo the agent penetrates pathogens and targets DNA and RNA. Upon activation by ultraviolet A light, this agent is able to form interstrand DNA and RNA crosslinks and prevents replication. Inactivation of leukocytes can prevent graft versus host disease upon transfusion.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v6 classification system.
A finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v6 classification system.
Anal cancer with no evidence of distant metastasis. (from AJCC 6th Ed.)
Anal cancer with distant metastasis. (from AJCC 6th and 7th Eds.)
Anal cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Anal cancer with no evidence of metastasis to regional lymph nodes. (from AJCC 6th and 7th Eds.)
Anal cancer with metastasis in perirectal lymph node(s). (from AJCC 6th and 7th Eds.)
Anal cancer with metastasis in unilateral internal iliac and/or inguinal lymph node(s). (from AJCC 6th and 7th Eds.)
Anal cancer with metastasis in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes. (from AJCC 6th and 7th Eds.)
Anal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Anal cancer with no evidence of a primary tumor. (from AJCC 6th and 7th Eds.)
Anal cancer with tumor size 2 centimeters or less in greatest dimension. (from AJCC 6th and 7th Eds.)
Anal cancer with tumor size more than 2 centimeters, but 5 centimeters or less, in greatest dimension. (from AJCC 6th and 7th Eds.)
Anal cancer with tumor size more than 5 centimeters in greatest dimension. (from AJCC 6th and 7th Eds.)
Anal cancer with tumor of any size that invades adjacent organ(s); e.g. vagina, urethra, bladder. Direct invasion of the rectal wall, perirectal skin, subcutaneous tissue, or the sphincter muscle(s) is not classified as T4. (from AJCC 6th and 7th Eds.)
Anal cancer in which the primary tumor cannot be assessed. (from AJCC 6th and 7th Eds.)
Anal cancer in situ. (from AJCC 6th and 7th Eds.)
The orally bioavailable hydrochloride salt of a synthetic, small-molecule ghrelin mimetic with appetite-stimulating and anabolic activities. Anamorelin binds to and stimulates the growth hormone secretagogue receptor (GHSR) centrally, thereby mimicking the appetite-stimulating and growth hormone-releasing effects of grhelin. Stimulation of GHSR may also reduce the production of the pro-inflammatory cytokines TNF-alpha and interleukin-6, which may play a direct role in cancer-related loss of appetite.
An immunoconjugate consisting of an anti-CD19 monoclonal antibody conjugated to the maytansinoid DM4, a derivative of the cytotoxic agent maytansine (DM1), with potential antineoplastic activity. Anti-CD19-DM4 conjugate SAR3419 targets the cell surface antigen CD19, found on a number of B-cell-derived cancers. Upon antibody/antigen binding and internalization, the immunoconjugate releases DM4, which binds to tubulin and disrupts microtubule assembly/disassembly dynamics, resulting in inhibition of cell division and cell growth of CD19-expressing tumor cells.
A fully human anti-CD19 monoclonal antibody directed against the B-cell-specific membrane protein CD-19 with potential antineoplastic activity. Anti-CD19 monoclonal antibody MDX-1342 binds to CD19, depleting and eliminating CD19-expressing B-cells. CD19 is widely expressed during B-cell development, from pro-B-cell to early plasma cell stages.
A humanized monoclonal antibody directed against the cell surface receptor CD30 with potential immunotherapeutic activity. Anti-CD30 monoclonal antibody XmAb2513 specifically binds to the CD30 antigen, which may result in a cytotoxic T lymphocyte (CTL) response against CD30-expressing tumor cells. CD30, a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on activated lymphocytes transiently and is constitutively expressed in hematologic malignancies including Hodgkin's disease and some T-cell non-Hodgkin's lymphomas.
An immunoconjugate consisting of the humanized monoclonal antibody huMy9-6 conjugated to the cytotoxic maytansinoid DM4 with potential antineoplastic activity. The monoclonal antibody portion of anti-CD33 monoclonal antibody-DM4 conjugate AVE9633 specifically binds to the cell surface antigen CD33 expressed on myeloid leukemia cells; upon internalization, the DM4 moiety is released, binds tubulin, and disrupts microtubule assembly/disassembly dynamics, resulting in the inhibition of cell division and cell growth in myeloid leukemia cells that express CD33. CD33 is expressed on normal non-pluripotent hematopoietic stem cells as well as on myeloid leukemia cells.
A fully human monoclonal antibody directed against the cell surface glycoprotein CD-38 with potential antineoplastic activity. The binding of anti-CD38 monoclonal antibody to natural killer (NK) cells mimics the normal CD38-CD31 interaction on the NK cell surface. CD38 is also present on multiple myeloma (MM) cells and plasma leukemia cells; this agent may preferentially bind these cells, triggering antitumoral antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). CD38, a cell surface glycoprotein, is present on various immune cells and has been shown to regulate the cytotoxic response of activated NK cells.
A bivalent recombinant fusion protein immunotoxin derived from the anti-CD3 monoclonal antibody UCHT1 with potential antineoplastic activity. Anti-CD3 immunotoxin A-dmDT390-bisFv(UCHT1) consists of 1-390 amino acid residues of chain A diphtheria toxin (DT) joined via a spacer to the Fv fragment of UCHT1, which is connected to a second UCHT1 Fv fragment via a disulfide bond (hence the ""bisFv"" designation); the addition of the second Fv fragment overcomes the steric hindrance of immunotoxin binding due to the large N-terminal DT domain. Once inside target T cells, the DT moiety catalyzes the transfer of the ADP-ribose moiety of NAD to diphthamide, a posttranslationally modified histidine residue found in elongation factor 2 (EF-2); inactivation of EF-2, disruption of polypeptide chain elongation, and cell death ensue. CD3 is a complex of five cell-surface polypeptides associated with the T cell receptor (TCR) complex.
A high affinity IgG1 monoclonal antibody with potential immunotherapeutic activity. Anti-CD45 monoclonal antibody AHN-12 recognizes CD45, a transmembrane protein tyrosine phosphatase that is expressed on the surface of normal and malignant hematopoietic cells.
A bispecific monoclonal antibody (BsMAb) consisting of the Fab fragment of an anti-CEA monoclonal antibody (F6) coupled to the Fab fragment of an anti-DTPA-In monoclonal antibody (734) with potential radioimmunotherapeutic activity. In a two-step pretargeted radioimmunotherapeutic approach, this BsMAb, localizing to CEA-expressing tumor cells via the F6 Fab fragment, is introduced into patient first, followed by injection of indium 131-radiolabeled DTPA, which is recognized by the 734 Fab fragment of the BsMAb. Accordingly, a potentially lethal dose of indium 131 is delivered specifically to CEA-expressing tumor cells while minimizing radiotoxicity to normal tissues. CEA (carcinoembryonic antigen) is a tumor antigen overexpressed in many cancer types, including gastrointestinal, breast, non-small cell lung, and thyroid cancers. DTPA (diethylenetriaminepentaacetic acid) is a bivalent hapten.
A human/murine chimeric monoclonal antibody directed against endoglin (CD105) with potential antiangiogenic and antineoplastic activities. Anti-endoglin monoclonal antibody TRC105 binds to endoglin, which may result in inhibition of tumor angiogenesis and decreased tumor cell proliferation. The glycoprotein endoglin is a transforming growth factor beta-1 (TGF beta-1) accessory receptor that is highly expressed on tumor vessel endothelial cells and appears to be essential for angiogenesis.
A fusion protein immunotoxin consisting of a humanized, single-chain monoclonal antibody Fab fragment specific for the epithelial cell adhesion molecule (EpCAM) conjugated with a modified bouganin cytotoxin with potential antineoplastic activity. Citatuzumab bogatox binds to EpCAM, delivering modified bouganin cytotoxin directly to EpCam-positive tumor cells, which may result in the inhibition of tumor cell protein synthesis and tumor cell death. EpCAM, a cell surface protein, is expressed by a variety of tumor cells and is frequently found in head and neck cancers. Bouganin is a plant-derived ribosome-inactivating protein (RIP), a toxic plant N-glycosidase that depurinates the universally conserved alpha-sarcin loop of ribosomal rRNA, inactivating the ribosome and preventing protein synthesis. Compared to unmodified bouganins, modified bouganins may have a reduced propensity to activate human T cells.
A synthetic antisense oligodeoxynucleotide (AS ODN) targeting hypoxia-inducible factor-1alpha (HIF-1alpha) with potential antineoplastic activity. Anti-HIF-1alpha LNA antisense oligonucleotide EZN-2968 hybridizes with HIF-1alpha mRNA and blocks t HIF-1 alpha protein expression, which may result in the inhibition of angiogenesis, the inhibition of tumor cell proliferation, and apoptosis. HIF-1alpha, normally activated in response to hypoxia-induced stress, is a key transcription regulator of a large number of genes important in cellular adaptation to low-oxygen conditions, including angiogenesis, cell proliferation, apoptosis, and cell invasion.
A recombinant, human monoclonal antibody directed against the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Anti-IGF-1R recombinant monoclonal antibody BIIB022 binds to membrane-bound IGF-1R, preventing binding of the ligand IGF-1 and the subsequent triggering of the PI3K/Akt signaling pathway; inhibition of this survival signaling pathway may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. The activation of IGF-1R, a tyrosine kinase and a member of the insulin receptor family, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been highly implicated in tumorigenesis and metastasis.
A humanized monoclonal antibody directed against nerve growth factor (NGF), a modulator of nociceptor function, with potential analgesic activity. Tanezumab binds to NGF and prevents NGF binding to its high affinity, membrane-bound, catalytic receptor tropomyosin-related kinase A (TrkA), which is present on sympathetic and sensory neurons; reduced stimulation of TrkA by NGF inhibits the pain-transmission activities of these neurons. NGF, a neurotrophin, is critical to the growth and maintenance of sympathetic and sensory neurons. In addition, NGF may induce mast cells to release inflammatory proteins and may induce the upregulation of substance P and other pain-related peptides in sympathetic and sensory neurons. Upon neurotrophin binding, TrkA phosphorylates itself and members of the MAPK pathway, mediating the multiple neuronal effects of NGF.
A humanized monoclonal antibody directed against human PD-1 (programmed cell death 1; PDCD1), with immunomodulating and antitumor activities. Pidilizumab blocks interaction between the receptor PD-1 with its ligands, PD-1 ligand 1 (PD-1L1) and PD-1 ligand 2 (PD-1L2), resulting in the attenuation of apoptotic processes in lymphocytes, primarily effector/memory T cells, and the augmentation of the anti-tumor activities of NK cells. PD-1 is an inhibitory receptor belonging to the B7-receptor family that is expressed on lymphocytes and myeloid cells; its ligands, PD-1L1 and PD-1L2, are expressed not only by hematopoietic cells but also by cells in non-lymphoid tissues.
A fully human monoclonal agonist antibody directed against the extracellular domain of human TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptor 2 (TR-2) with potential antineoplastic activity. Conatumumab mimics the activity of native TRAIL, binding to and activating TR-2, thereby activating caspase cascades and inducing tumor cell apoptosis. TR-2 is expressed by a variety of solid tumors and cancers of hematopoietic origin.
An orally bioavailable, small-molecule receptor tyrosine kinase inhibitor with potential antiangiogenic and antineoplastic activities. Apatinib selectively binds to and inhibits vascular endothelial growth factor receptor 2, which may inhibit VEGF-stimulated endothelial cell migration and proliferation and decrease tumor microvessel density. In addition, this agent mildly inhibits c-Kit and c-SRC tyrosine kinases.
A proprietary multiherbal topical cream based on Chinese herbal medicine with potential antineoplastic, antiviral, antibacterial and immunostimulatory activities. Arnebia Indigo Jade Pearl topical cream contains 12 ingredients including 9 herbs infused in sesame oil, with an additional three powdered ingredients and beeswax added to the infused oil to create the salve. The purported mechanism(s) of action is unclear due to the complexity of the herbal mixture.
A small molecule inhibitor of the serine/threonine protein kinase Aurora kinase with potential antineoplastic activity. Aurora kinase inhibitor BI 811283 binds to and inhibits Aurora kinases, resulting in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation.
A synthetic small molecule Aurora kinase (AK) inhibitor with potential antineoplastic activity. Aurora kinase inhibitor SNS-314 selectively binds to and inhibits AKs A and B, which may result in the inhibition of cellular division and proliferation in tumor cells that overexpress AKs. AKs are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis.
An orally bioavailable small molecule multi-kinase inhibitor with antineoplastic activity. Aurora kinase/VEGFR 2 inhibitor CYC116 inhibits Aurora kinases A and B and vascular endothelial growth factor receptor 2 (VEGFR2), resulting in disruption of the cell cycle, rapid cell death, and the inhibition of angiogenesis. Aurora kinases are serine/threonine protein kinases that are only expressed in actively dividing cells and are critical in division or mitosis. VEGFR2 is a receptor tyrosine kinase that appears to account for most of the mitogenic and chemotactic effects of vascular endothelial growth factor (VEGF) on adult endothelial cells.
A cancer vaccine comprised of autologous dendritic cells (DCs) that have been transduced ex vivo with an adenoviral vector containing the CCL21 gene with potential immunostimulatory and antineoplastic activities. Upon intratumoral administration, autologous dendritic cell-adenovirus CCL21 vaccine expresses the chemokine CCL21, which may induce an antitumoral cytotoxic immune response in the tumor microenvironment. CCL21 [chemokine (C-C motif) ligand 21] has been shown to attract antigen presenting cells (APCs), like leukocytes and DCs, and natural killer (NK) cells and their T-cell effectors to induce a cytotoxic immune response.
A therapeutic cancer vaccine consisting of autologous dendritic cells (DCs) fused with autologous tumor cells with potential immunostimulatory and antineoplastic activities. Autologous dendritic cell-tumor fusion vaccine is generated in vitro by mixing DCs and irradiated tumor cells harvested from individual patients and treating them with polyethylene glycol (PEG) to produce DC-tumor cell fusion hybrid cells. Upon administration, autologous dendritic cell-tumor fusion vaccine may elicit antitumor humoral and cellular immune responses.
A patient-specific cancer vaccine directed against the soluble protein idiotype of an individual follicular lymphoma with potential antineoplastic activity. A patient-specific follicular lymphoma-derived anti-idiotype vaccine may be composed of a patient-specific, synthetic idiotype-related peptide (such as one corresponding to a hypervariable region of an IgG heavy chain) conjugated to the immunostimulant carrier protein keyhole limpet hemocyanin (KLH). Upon administration, this vaccine may induce an idiotype-specific cytotoxic T-lymphocyte (CTL) response against follicular lymphoma cells expressing the idiotype, resulting in tumor cell lysis.
A preparation of cytotoxic T-lymphocytes (CTL), specifically reactive to the Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and 2, with potential antineoplastic activity. Autologous dendritic cells and EBV-infected lymphoblastoid cell lines (LCL) from patients with EBV-positive nasopharyngeal carcinoma (NPC) are transduced with an LMP1/LMP2-expressing adenoviral vector, are irradiated, and then are used to stimulate and expand autologous CTL to produce autologous LMP1-/LMP2-specific CTL ex vivo. Administration of autologous LMP1-/LMP2- specific cytotoxic T-lymphocytes may result in a specific CTL response against tumor cells expressing LMP1 and LMP2, resulting in cell lysis and inhibition of tumor cell proliferation in vivo. Among a limited set of viral antigens expressed by NPC cells, LMP1 and LMP2 are weak immunogens which, nevertheless, are capable of inducing a T-lymphocyte response.
A multipeptide vaccine consisting of five peptides derived from the bcr-abl p210-b3a2 breakpoint fusion protein with potential antineoplastic activity. Vaccination with bcr-abl p210-b3a2 breakpoint-derived multipeptide vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells that express the bcr-abl p210-b3a2 breakpoint fusion protein. In chronic myelogenous leukemia (CML), fusion genes typically result from the fusion of either bcr exon b2 or exon b3 to abl exon a2, resulting in either a b3a2 or a b2a2 gene fusion product.
The hydrochloride salt form of losoxantrone, an anthrapyrazole-based antineoplastic antibiotic. Losoxantrone intercalates into DNA, induces single- and double-stranded DNA breaks and inhibits topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Losoxantrone is less cardiotoxic than doxorubicin.
An orally active, selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor AZD8330 specifically inhibits mitogen-activated protein kinase kinase 1 (MEK or MAP/ERK kinase1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.
An inhibitor of MET tyrosine kinase with potential antineoplastic activity. MET tyrosine kinase inhibitor BMS-777607 binds to c-Met protein, or hepatocyte growth factor receptor (HGFR), preventing binding of hepatocyte growth factor (HGF) and disrupting the MET signaling pathway; this agent may induce cell death in tumor cells expressing c-Met. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays an important role in tumor cell proliferation, survival, invasion, and metastasis, and in tumor angiogenesis.
An orally bioavailable small molecule, c-Met inhibitor with potential antineoplastic activity. MET receptor tyrosine kinase inhibitor SGX523 specifically binds to c-Met protein, or hepatocyte growth factor receptor (HGFR), preventing binding of hepatocyte growth factor (HGF) and disrupting the MET signaling pathway; this agent may induce cell death in tumor cells expressing c-Met. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays an important role in tumor cell proliferation, survival, invasion, and metastasis, and in tumor angiogenesis.
A cancer vaccine consisting of a proprietary, recombinant modified vaccinia Ankara (MVA) viral vector encoding an epitope of human epidermal growth factor receptor 2 (HER2) with potential antineoplastic activity. Upon administration, modified vaccinia Ankara (Bavarian Nordic)-HER2 vaccine may stimulate the host immune system to mount humoral and cytotoxic T lymphocyte responses against HER2-expressing tumor cells, resulting in tumor cell lysis. HER2, also known as ErbB-2, is a tyrosine kinase growth factor receptor and a member of the epidermal growth factor receptor family; it plays a significant role in the pathogenesis of some breast cancers.
A cancer vaccine consisting of a recombinant modified vaccinia Ankara (MVA) viral vector encoding genes for prostate specific antigen (PSA) and prostate acid phosphatase (PAP) with potential immunostimulatory and antineoplastic activities. Upon administration, MVA-PSA-PAP prostate cancer vaccine expresses PSA and PAP peptides, which may elicit humoral and cellular immune responses against prostate cancer cells expressing PSA and PAP. Multi-antigen vaccine therapy may be more efficacious than single-antigen therapy vaccine therapy.
Magnesium ion requiring two electrons to return to its elemental state.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysates from malignant glioma cells with potential immunostimulatory and antineoplastic activities. Upon administration, malignant glioma tumor lysate-pulsed autologous dendritic cell vaccine exposes the immune system to undefined malignant glioma tumor-associated antigens (TAAs), which may result in anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against glioma cells and glioma cell lysis.
A sodium salt form of acediasulfone, a long-acting prodrug of dapsone, used in the treatment of leprosy.
An indole derivative and third-generation selective estrogen receptor modulator (SERM) with potential antineoplastic activity. Upon administration, bazedoxifene specifically binds to estrogen receptors in responsive tissues, including liver, bone, breast, and endometrium. The resulting ligand-receptor complex is translocated to the nucleus where, depending on the tissue type, it either promotes or suppresses the transcription of estrogen-regulated genes. Bazedoxifene acts as an estrogen antagonist in uterine and breast tissue, thereby blocking the proliferative effects of estrogen-binding to ER-positive cells in these tissues. Bazedoxifene functions as an estrogen agonist in lipid metabolism, thereby decreasing total and LDL cholesterol levels. In bone, it decreases bone resorption and bone turnover and increases bone mineral density.
An indication that a heart beat was detected and accepted as conforming to the measurement standards.
A phosphorylated biguanide derivative with antihyperglycamic activity. Benfosformin is associated with an increased risk of lactic acidosis.
The calcium salt form of benzoyl-PAS, an analog of aminobenzoic acid used to treat tuberculosis. Calcium benzoyl-PAS is better tolerated by patients, leading to higher compliance.
The dimesylate salt form of bisnafide, a bis-naphthalimide compound with anticancer activity. Bisnafide selectively intercalates guanine-cytosine (GC) rich regions of DNA, thereby interfering with DNA replication machinery and activity of topoisomerase II. As a result, this agent causes potent cytotoxicity.
A description of the boundary findings or features of a sample.
Manganese ion requiring two electrons to return to its elemental state.
A monofloral honey with potential wound repair and antibacterial activities. Manuka honey is produced by bees fed on the flowers of the New Zealand Manuka bush (Leptospermum scoparium). Manuka honey contains a significant higher concentration of the 1,2-dicarbonyl compound methylglyoxal, which may account for its antibacterial activity; this agent may release small amounts of hydrogen peroxide which may also contribute to its antibacterial activity. Manuka honey has been reported to stimulate the formation of new blood capillaries and the growth of fibroblasts and epithelial cells when applied topically to wounds.
A small molecule with mast cell stabilizing activity. Mast cell stabilizer TF002 inhibits the formation of lipid rafts of mast cell membranes that contain the signaling machinery which triggers the release of mast cell allergic and inflammatory mediators. Inhibition of lipid raft assembly by this agent results in mast cell stabilization, preventing mast cell degranulation and the release of the inflammatory mediators involved in type I allergic reactions (histamine, leukotrienes, prostaglandins, and cytokines). The assembly of the signaling machinery in mast cell lipid rafts, specialized membrane microdomains rich in cholesterol and sphingolipids, is initiated by IgE binding to its receptor on the mast cell surface; subsequently, allergens crosslink with the IgE/receptor complex and other proteins and lipids are recruited into the signaling machinery.
Problem associated with the energy to operate the device.
An micronutrient-fortified fermented dairy product with potential positive immunomodulatory activity. Micronutrient-fortified probiotic yogurt contains various micronutrients in addition to beneficial microorganisms, such as strains of Lactobacillus. Probiotic Lactobacillus strains have been shown to protect against gastrointestinal and urogenital infections, to moderate diarrheal episodes, and to increase CD4 T-lymphocyte counts. In immunocompromised subjects, micronutrient supplementation may also increase CD4 T-lymphocyte counts.
A primary systemic vasculitis of small- and some medium-sized vessels. It is characterized by a tropism for kidneys and lungs, positive association with anti-neutrophil cytoplasmic antibodies (ANCA), and a paucity of immunoglobulin deposits in vessel walls.
Any substance that inhibits mitogen-activated protein kinase kinase (MEK), an enzyme that catalyzes the addition of a phosphate group to a mitogen-activated protein kinase. Inhibition of mitogen-activated protein kinase kinase results in the inhibition of cell proliferation.
A pyrazolobenzodiazepine small molecule with potential antiangiogenesis and antineoplastic activities. Mitosis-angiogenesis inhibitor (MAI) R1530 inhibits multiple receptor tyrosine kinases involved in angiogenesis, such as vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, platelet-derived growth factor receptor (PDGFR) beta, FMS-like tyrosine kinase (Flt)-3, and fibroblast growth factor receptor (FGFR) -1, -2. In addition, this agents exhibits anti-proliferative activity by initiating mitotic arrest and inducing apoptosis.
A cancer vaccine containing a mixture of killed bacteria with potential immunostimulatory and antineoplastic activities. Mixed bacteria vaccine (MBV or Coley's toxins) consists of a pyrogenic bacterial lysate derived from Serratia marcescens and Streptococcus pyogenes; the active components in the lysate may be lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall of Serratia, and streptokinase, an enzyme produced by Streptococcus pyogenes. LPS has been shown to stimulate the host humoral immune response and induce the release of various antitumor cytokines such as tumor necrosis factor (TNF) and interleukin-12 (IL-12).
The hydrochloride salt form of acotiamide, a prokinetic agent with gastrointestinal (GI) motility-enhancing activity. Although the exact mechanism by which acotiamide exerts its effect has yet to be fully elucidated, this agent appears to inhibit acetylcholinesterase (AchE), an enzyme responsible for the breakdown of acetylcholine (Ach). Increased Ach concentrations lead to an improvement of gastric emptying and GI motility and eventually to a reduction of dyspepsia symptoms.
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor.
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes.
Breast cancer with distant metastasis. (from AJCC 6th Ed.)
Breast cancer with no regional lymph node metastasis. (from AJCC 6th and 7th Eds.)
Breast cancer with metastasis to movable ipsilateral level I, II axillary lymph node(s). (from AJCC 6th and 7th Eds.)
Breast cancer with metastases in ipsilateral axillary lymph nodes fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis. (from AJCC 6th Ed.)
Breast cancer with metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures. (from AJCC 6th and 7th Eds.)
Breast cancer with metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis. (from AJCC 6th Ed.)
Breast cancer with metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node involvement, or in clinically apparent ipsilateral internal mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. (from AJCC 6th Ed.)
Breast cancer with metastasis in ipsilateral infraclavicular lymph node(s). (from AJCC 6th and 7th Eds.)
Breast cancer with metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s). (from AJCC 6th and 7th Eds.)
Breast cancer with metastasis in ipsilateral supraclavicular lymph node(s). (from AJCC 6th and 7th Eds.)
Breast cancer in which regional lymph nodes cannot be assessed. (from AJCC 6th and 7th Eds.)
Breast cancer with no evidence of primary tumor. (from AJCC 6th Ed.)
Breast cancer with tumor size 2.0 cm or less in greatest dimension. (from AJCC 6th Ed.)
Breast cancer with tumor size more than 2.0 cm, but not more than 5.0 cm in greatest dimension. (from AJCC 6th Ed.)
Breast cancer with tumor size more than 5.0 cm in greatest dimension. (from AJCC 6th Ed.)
A propenamide-based agent with antineoplastic activity. Bromacrylide has been shown to decrease tumor growth in animal models, but is accompanied with severe toxicity, including severe bone marrow suppression and weight loss.
A bromine-containing agent reported to have antifungal and antibacterial activity.
Simulations used to describe the motion of molecules in solution, generally discounting the effects of inertia.
An electrocardiographic finding of ventricular tachycardia incorporating both bundle branches into the reentry circuit.
A proprietary antibody-based single-chain polypeptide with B cell-depleting activity. Significantly smaller than a whole antibody, CD20-targeted polypeptide TRU-015 binds specifically to the B cell-specific cell surface antigen CD20 with full immunoglobulin Fv fragment-type target binding activity and full immunoglobulin Fc fragment-type effector function. This agent transiently depletes CD20-bearing B cells by inducing B cell -directed complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) and B cell apoptosis.
A population of T cells that have been sensitized to vaccine tumor antigen(s) in vivo; collected from the patient; co-stimulated with antibodies to the T-cell cell surface proteins CD3 and CD28 and expanded ex vivo; and then infused into the same patient. CD3, part of the T cell receptor complex, and CD28, a T-cell surface-associated co-stimulatory molecule, are both required for full T-cell activation. Adoptive transfer of CD3/CD28 costimulated vaccine-primed autologous T-cells may induce the production of interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and associated antitumor effects and a graft-versus-tumor (GVT) response.
An indication that expression of CD52 has been detected in a sample of neoplastic cells.
A cancer vaccine, consisting of alphavirus vector-derived virus-like replicon particles expressing the 9-amino-acid carcinoembryonic antigen peptide (CAP) 1-6D, with potential antineoplastic activity. Vaccination with this agent may elicit a cytotoxic T lymphocyte (CTL) immune response against CEA-expressing tumor cells.
An orally bioavailable receptor tyrosine kinase inhibitor with potential antineoplastic activity. AMG 706 selectively targets and inhibits vascular endothelial growth factor (VEGFR), platelet-derived growth factor (PDGFR), Kit, and Ret receptors, thereby inhibiting angiogenesis and cellular proliferation.
The heavy chain of the immunoglobulin, IgA, is defective. This is the second most common type of multiple myeloma (~20%).
The heavy chain of the immunoglobulin, IgD, is defective. This multiple myeloma subtype is very rare (~1%).
The heavy chain of the immunoglobulin, IgE, is defective. This multiple myeloma subtype is extremely rare.
The heavy chain, IgG, of the immunoglobulin is defective. This is the most common type of multiple myeloma (>50%).
The heavy chain, IgM, of the immunoglobulin is defective. This finding is seen in other lymphocytic/plasmacytic disorders as well, including Waldenstrom macroglobulinemia.
Only the light chain (kappa or lambda) of the immunoglobulin is defective.
A leiomyoma characterized by the presence of abundant myxoid matrix.
Criteria established for assigning high-frequency microsatellite instability (MSI-H) in cancers requiring that at least two of five markers (BAT25, BAT26, D2S123, D5S346, D17S250) score positive for MSI.
A cancer vaccine containing HLA class I- and II-binding peptides derived from the NY-ESO-1/LAGE-1 cancer/testis antigen with potential immunostimulatory and antineoplastic activities. Upon administration, NY-ESO-1/LAGE-1 HLA class I/II peptide vaccine may induce a cytotoxic immune response against tumor cells that over-express NY-ESO-1/LAGE-1. Rarely expressed by normal cells, the NY-ESO-1/LAGE-1 cancer/testis antigen has been shown to be preferentially expressed on the surface of some cancer cell types.
A recombinant nonapeptide used as an antineoplastic vaccine. NY-ESO-1b peptide vaccine contains the amino acid sequence SLLMWITQC, derived from the cancer-testis tumor antigen (NY-ESO-1), which is expressed on tumor cells of many different types, including melanomas. Vaccination with this peptide vaccine may elicit strong humoral and cellular immune responses to NY-ESO-1-expressing cancers.
A nanoparticle albumin-bound formulation of the taxane docetaxel with antineoplastic activity. Docetaxel is a semi-synthetic, second-generation taxane derived from a compound found in the European yew tree Taxus baccata. Docetaxel binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell-cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and displays immunomodulatory and pro-inflammatory properties by inducing various mediators of the inflammatory response. This nanoparticle albumin-bound formulation solubilizes docetaxel without the use of the nonionic solubilizer Cremophor ELP, permitting the administration of larger doses of docetaxel while avoiding Cremophor ELP-associated toxicity.
The macrolide antibiotic rapamycin bound to nanoparticle albumin with immunosuppressant (see sirolimus) and potential antiangiogenic and antineoplastic activities. Rapamycin binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate a complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. In turn, inhibition of mTOR may result in the inhibition of the phosphatidylinositol 3 (PI-3) kinase/Akt pathway and vascular endothelial cell growth factor (VEGF) secretion, which may result in decreased tumor cell proliferation and tumor angiogenesis. The binding of water-insoluble rapamycin to nanoparticle albumin permits the albumin-mediated endocytosis of rapamycin by tumor cells and endothelial cells.
A proprietary preparation of natural human interferon alpha (IFN alpha) with potential immunomodulatory and antineoplastic activities. Natural human interferon alpha OPC-18 binds to cell-surface IFN alpha receptors (IFNARs), resulting in the transcription and translation of genes whose products mediate antiviral, antiproliferative, and immune-modulating effects. IFN alpha is a type I interferon produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products and is the primary interferon produced by virus-induced leukocyte cultures. In addition to its pronounced antiviral activity, it activates NK cells.
Autologous dendritic cells (DCs) transduced with the replication-deficient adenoviral vector Ad5F53 encoding the Epstein-Barr virus (EBV) transmembrane latent membrane proteins 1 and 2 (LMP1/LMP2) with potential immunostimulatory activity. Vaccination with Ad5F35-LMP1/LMP2-transduced autologous dendritic cells may stimulate a specific cytotoxic T-lymphocyte (CTL) response against LMP1- and LMP2-expressing tumor positive cells, resulting in tumor cell lysis and inhibition of tumor cell proliferation. LMP1 and LMP2 are expressed in various malignancies including nasopharyngeal cancer and EBV-positive Hodgkins disease.
Remission with persistent lymphoid nodules in the bone marrow.
An electrocardiographic finding of changes in the ST segment and T wave that do not meet criteria for ischemia or infarction.
An electrocardiographic finding of an irregular, u or v shaped deflection within the contour of the T wave. (CDISC)
A prodrug of the acyclic nucleoside phosphonate analogue 9-(2-phosphonylmethoxyethyl)guanine (PMEG) with potential antineoplastic activity. Formulated to selectively accumulate in lymphocytes, nucleotide analogue GS 9219 is converted to its active metabolite, PMEG diphosphate (PMEGpp), via enzymatic hydrolysis, deamination, and phosphorylation; subsequently, PMEGpp is incorporated into nascent DNA chains by DNA polymerases, which may result in the termination of DNA synthesis, S-phase cell cycle arrest, and the induction of apoptosis in susceptible lymphoma cell populations.
An outcome of observation represented as a text, qualitative, or quantitative parameter, code, image, graph, etc.
A tumor component characterized by the presence of a diffuse, homogeneous population of tumor cells (oligodendroglial cells) with round nuclei and clear cytoplasm. The infiltrate has a honeycomb appearance. An oligodendroglial component can be seen in central nervous system tumors including glioblastomas and mixed gliomas.
An adenovirus serotype 5 strain, selectively replication competent in cells defective in the Rb/p16 tumor suppressor pathway, with potential oncolytic activity. Oncolytic adenovirus Ad5-DNX2401 contains an integrin binding RGD-4C motif, allowing Coxsackie adenovirus receptor-independent infection of tumor cells, which are often deficient for Coxsackie and adenovirus receptors (CARs). Selectively replication competent in cells that are defective in retinoblastoma gene (Rb) or cyclin-dependent kinase inhibitor-2A (p16), active replication of oncolytic adenovirus Ad5-Delta 24RGD in tumor cells may induce oncolysis or cell lysis. As integral components of the late G1 restriction point, the Rb gene product and p16 are negative regulators of the cell cycle; ovarian cancer cells and non-small cell lung cancer cells may be defective in the Rb/p16 pathway.
An orally bioavailable microencapsulated formulation of diindolylmethane, an indole phytonutrient found in cruciferous vegetables, with estrogen-modulating, antiandrogenic, and potential antineoplastic activities. As a dimer of indole-3-carbinol, diindolylmethane (DIM) modulates estrogen balance by reducing the levels of 16-hydroxy estrogen metabolites and increasing the formation of beneficial 2-hydroxy estrogen metabolites. DIM also antagonizes androgen receptor activity, which may result in diminished cell proliferation and apoptosis in susceptible tumor cell populations. Pure DIM, which is relatively hydrophobic, is poorly absorbed after oral administration. This oral formulation, which consists of DIM, d-alpha-tocopheryl acid succinate, phosphatidylcholine, and silica microencapsulated in starch, significantly improves the gastrointestinal absorption of DIM.
An oral preparation of picoplatin, a third generation platinum compound with antineoplastic activity. Designed to overcome platinum drug resistance, picoplatin alkylates DNA, forming both inter- and intra-strand cross-linkages, resulting in inhibition of DNA replication and RNA transcription and the induction of apoptosis. Because of the increase in steric bulk around the platinum center, there is a relative reduction in the inactivation of picoplatin by thiol-containing species such as glutathione and metallothionein in comparison to cisplatin.
Problem associated with an adjustment that surpasses a set of criteria.
A controlled-release, intratumoral paclitaxel formulation in which paclitaxel is incorporated into a thermosensitive, biodegradable triblock copolymer consisting of poly(lactide-co-glycolide) (PLGA) and polyethylene glycol (PEG). Upon intratumoral injection, paclitaxel is released slowly and continuously into tumor tissues from the gelled thermosensitive triblock copolymer over a period of 4 to 6 weeks; in tumor cells, paclitaxel binds to tubulin and inhibits the disassembly-assembly dynamics of microtubules, resulting in cell cycle arrest and cell death. The thermosensitive triblock copolymer component of this formulation transforms from a water-soluble polymer at room temperature to a water-insoluble, biodegradable gel depot at body temperature; intratumoral controlled-release of paclitaxel from the gel minimizes systemic exposure to paclitaxel and the paclitaxel toxicity profile.
A phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor BGT226 specifically inhibits PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability; apoptotic cell death may ensue. Bax is a member of the proapoptotic Bcl2 family of proteins.
An ovine atadenovirus encoding E. coli purine nucleoside phosphorylase (PNP) with prodrug activating activity. Under the control of a prostate-directed promoter, PNP-expressing atadenovirus vaccine FP253 expresses PNP in prostate tissue only after intraprostatic administration; this enzyme catalyzes systemically administered fludarabine prodrug into the active agent, 2-fluoroadenine. Localized prodrug activation provides prostate-targeted chemotherapy, potentially reducing systemic side effects.
An electrocardiographic finding of tachycardia that is usually terminated by the administration of adenosine. Usually, it is a result of cAMP-mediated triggered activity and typically originates from the right ventricular outflow tract. This type of tachycardia occurs in patients with apparently normal hearts.
An adenoviral vector engineered to express the herpes simplex virus thymidine kinase (HSV-tk) gene, which, when administered in conjunction with a synthetic acyclic guanosine analogue, possesses potential antineoplastic activity. Aglatimagene besadenovec is transduced into tumor cells, sensitizing tumor cells that overexpress HSV-tk to synthetic acyclic guanosine analogues. Subsequently, a low dose of a synthetic acyclic guanosine analogue such as valacyclovir (VCV) or ganciclovir (GCV) is given, which may preferentially kill tumor cells containing the adenoviral vector and overexpressing HSV-tk. Release of tumor-associated antigens (TAAs) by dying tumor cells may then stimulate an antitumor cytotoxic T lymphocyte (CTL) response.
A replication-deficient, recombinant adenovirus encoding human aquaporin-1 with potential membrane water channel activity. Upon transfection of salivary glands, adenovirus encoding human aquaporin-1 (AdhAQP1) directs human aquaporin-1 (hAQP1) expression in the apical and basolateral plasma membranes of salivary secretory cells, which may result in increased saliva production. hAQP1, a water channel protein, is one of several highly conserved water channel proteins that mediate water permeability in cells of water-transporting tissues.
A population of cells derived from adipose tissue with stem cell and wound repair activities. Adipose-derived regenerative cells (ADRC) consists of several cell types, such as adult stem cells, vascular endothelial cells, and vascular smooth muscle cells, among others. These cells contribute to wound repair through a variety of mechanisms by promoting blood vessel growth and blocking apoptosis. In addition, ADRC can differentiate into several tissue types, such as bone, cartilage, fat, skeletal muscle, smooth muscle and cardiac muscle.
An embolic material composed of microspheres of polyvinyl alcohol (PVA) polymers. These water-soluble, compressible microspheres may be used to encapsulate various therapeutic agents; drug-loaded microspheres can then be used as a drug delivery vehicle during embolization of tumor vasculature.
An embolic material composed of microspheres of polyvinyl alcohol (PVA) polymers loaded with doxorubicin hydrochloride with antineoplastic activity. Doxorubicin hydrochloride-loaded microspheres may be used as a drug delivery vehicle during embolization of tumor vasculature. Doxorubicin intercalates DNA, interferes with catalytic activity of topoisomerase II, and causes DNA adducts and other DNA damage, resulting in tumor cell growth inhibition and apoptosis. When used in tumor vasculature embolization, this preparation may provide more tumor-specific treatment with doxorubicin compared to the systemic administration of doxorubicin, thereby reducing the systemic toxicity of doxorubicin.
A morphologic appearance consisting of small, irregular regions of necrosis surrounded by dense accumulations of tumor cells; the tumor cells are more densely packed at the edge of the necrosis than in other regions of the tumor and thus appear to ""palisade"" around the necrotic zone.
An aminofurazan-derived inhibitor of Akt kinases with potential antineoplastic activity. Pan-AKT kinase inhibitor GSK-690693 binds to and inhibits Akt kinases 1, 2, and 3, which may result in the inhibition of protein phosphorylation events downstream from Akt kinases in the PI3K/Akt signaling pathway, and, subsequently, the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. In addition, this agent may inhibit other protein kinases including protein kinase C (PKC) and protein kinase A (PKA). As serine/threonine protein kinases which are involved in a number of biological processes, AKT kinases promote cell survival by inhibiting apoptosis and are required for glucose transport.
Partial response of multiple myeloma or plasma cell leukemia is characterized by a 50% or greater reduction in serum M-protein, and reduction in 24-hour urinary M-protein by 90% or more or to less than 200 mg/24 hours. If the serum and urine M-protein are unmeasurable (i.e., do not meet any of the following criteria: 1. serum M-protein at least 1 g/dL; 2. urine M-protein at least 200 mg/24 hours; a 50% or more decrease in the difference between involved and uninvolved free light chain levels is required in place of the M-protein criteria (provided the serum free light chain assay shows involved level at least 10 mg/dL and the serum free light chain is abnormal). If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, a 50% or more reduction in plasma cells is required in place of M-protein, provided the baseline bone marrow plasma cell percentage was 30% or more. In addition to the above listed criteria, a 50% or more reduction in the size of soft tissue plasmacytomas is also required, if present at baseline. Partial response requires two consecutive assessments made at any time before the institution of any new therapy, and no known evidence of progressive or new bone lesions if radiographic studies were performed; radiographic studies are not required to satisfy partial response requirements.
Patient identified to be at risk for an allergic reaction to contrast media.
A long-acting, pegylated recombinant variant of human granulocyte colony-stimulating factor (G-CSF) with immunomodulating activity. Pegylated granulocyte colony stimulating factor MAXY-G34 contains multiple non-naturally occurring lysines that have been introduced into alpha helixes of wild type human G-CSF as pegylation sites; other naturally occurring lysine residues have been removed to prevent pegylation and the variant G-CSF is pegylated with methoxypolyethylene glycol succinimidyl propionate (mPEG SPA) at three amino acid residues. Similar to endogenous G-CSF, this agent binds to and activates specific cell surface receptors, stimulating neutrophil progenitor proliferation and differentiation and selected neutrophil functions. A difference in the degree of pegylation may account for the extended half-life of this agent compared to pegfilgrastim which is pegylated at only one amino acid residue.
Philadelphia chromosome abnormality; t(9;22)(q34;q11) was not found; bcr/abl gene rearrangement was not tested; therefore it is not known if present or not.
Philadelphia chromosome abnormality; t(9;22)(q34;q11) was found; bcr/abl gene rearrangement was not tested; therefore it is not known if present or not.
Philadelphia chromosome abnormality; (9;22)(q34;q11) was not tested; therefore it is not known if it was present or not; bcr/abl gene rearrangement was found.
Philadelphia chromosome abnormality; t(9;22)(q34;q11) was not tested; therefore it is not known whether it is present or not; bcr/abl gene rearrangement was not tested; therefore it is not known whether it is present or not.
The 2,5-diphenylpiperazine salt of benzylpenicillin with antibacterial activity. Phenyracillin binds to and inactivates the penicillin binding proteins (PBPs) located inside the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This interrupts bacterial cell wall synthesis and results in the weakening of the bacterial cell wall, eventually causing cell lysis.
A B-cell acute leukemia occurring in childhood. It is characterized by the presence of lymphoblasts that carry a translocation between the BCR gene on chromosome 22 and the ABL1 gene on chromosome 9. It results in the production of the p190 kd or p210 kd fusion protein. It has an unfavorable clinical outcome.
An oral preparation of the flavonoid silybin with potential antioxidant and chemopreventive activities. Silybin, also known as silibinin, is a mixture of two stereoisomers, denoted silybin A and silybin B, and is the major active constituent of silymarin, a mixture of flavonolignans extracted from blessed milk thistle (Silybum marianum). Silybin modulates P-glycoprotein (P-gp)-mediated cellular efflux; has oxygen radical-scavenging effects; inhibits the arachidonic acid pathway; and inhibits various cytochrome P450 enzymes. This agent may also exhibit anti-angiogenic activity, possibly by inducing endothelial cell apoptosis via modulation of the transcription factor NF-kB, the Bcl-2 family of proteins, and caspases. Complexing silybin with phosphatidylcholine increases its bioavailability.
The hydrobromide salt form of pibrozelesin, a semisynthetic water-soluble derivative of the antineoplastic antibiotic duocarmycin B2, with antineoplastic activity. Activated by carboxyl esterase, pibrozelesin alkylates DNA by binding to adenine-thymine (A-T)-rich sequences in the minor groove of DNA, thereby inhibiting DNA replication and inducing apoptosis.
The pamoate salt form of a semisynthetic, orally active pivalate ester of ampicillin with antibacterial activity. Upon absorption, pivampicillin is hydrolyzed into its active form ampicillin by esterases. Ampicillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This interrupts bacterial cell wall synthesis and results in the weakening of the bacterial cell wall, eventually causing cell lysis.
A synthetic urethane derivative of pladienolide D with potential antineoplastic activity. Pladienolide derivative E7107 is generated from the 12-membered macrolide pladienolide D, one of several macrolides derived from the bacterium Streptomyces platensis Mer-11107. This agent appears to bind to the 130-kDa subunit 3 (spliceosome-associated protein 130; SAP130) of the splicing factor 3b (SF3b), resulting in inhibition of pre-messenger RNA splicing and the arrest of cell-cycle progression. The splicing factor SF3b is a multiprotein complex integral to the accurate excision of introns from pre-messenger RNA; the subunit SAP130 associates with U2 snRNP and is recruited to prespliceosomal complexes.
A proprietary botanical formulation derived from a traditional Chinese medicinal (TCM) plant with hematopoietic activity. Although the mechanism of action has yet to be fully elucidated, plant-derived hematopoiesis enhancer PG2 appears to stimulate multi-lineage progenitor cells that may be closely related to the hematopoietic stem cell. In both chemotherapy- and radiation therapy-induced animal models of myelosuppression, this agent has been shown to restore granulocyte, erythrocyte, and platelet counts to normal levels. Plant-derived hematopoiesis enhancer PG2 stimulates the production of numerous cytokines such as granulocyte-colony stimulating factor (G-CSF) and may stimulate the production of neuroendocrine hormones.
An acute myeloid leukemia with recurrent genetic abnormalities occurring in adults.
An acute myeloid leukemia with t(8;21)(q22; q22.1) occurring in adults.
An orally bioavailable inhibitor of CXCR4 with potential antineoplastic and antiviral activities. CXCR4 inhibitor MSX-122 binds to the chemokine receptor CXCR4, preventing the binding of stromal derived factor-1 (SDF-1) to the CXCR4 receptor and receptor activation, which may result in decreased tumor cell proliferation and migration. CXCR4, a chemokine receptor belonging to the GPCR (G protein-coupled receptor) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types; it is also a co-receptor for HIV entry into T cells.
The date of the most recent calibration event for an instrument.
An herbal preparation containing a defined quantity of specific cannabinoids formulated for oromucosal spray administration with potential analgesic activity. Nabiximols contains a standardized extract of tetrahydrocannabinol (THC), the non-psychoactive cannabinoid cannabidiol (CBD), other minor cannabinoids, flavonoids, and terpenes from two cannabis plant varieties. Cannabinoids interact with G protein-coupled cannabinoid 1 (CB1) receptors in the central nervous system, resulting in analgesic, euphoric, and anticonvulsive effects.
A centrally-acting neurokinin 1 (NK1) receptor antagonist with antidepressant and antiemetic activities. Casopitant competitively binds to and blocks the activity of the NK-receptor, thereby inhibiting NK1-receptor binding of the endogenous tachykinin neuropeptide substance P (SP), which may result in antiemetic effects. SP is found in neurons of vagal afferent fibers innervating the brain-stem nucleus tractus solitarii and the area postrema, which contains the chemoreceptor trigger zone (CTZ), and may be elevated in response to chemotherapy. The NK-receptor is a G-protein receptor coupled to the inositol phosphate signal-transduction pathway and is found in both the nucleus tractus solitarii and the area postrema.
A cationic liposome preparation of paclitaxel with antineoplastic activity. Paclitaxel, the active ingredient in cationic liposome-encapsulated paclitaxel, binds to tubulin and inhibits the disassembly of microtubules, resulting in the inhibition of mitosis and cellular proliferation, and apoptosis. Cationic liposome encapsulation of paclitaxel allows the delivery of high doses of paclitaxel to target tissues while minimizing systemic toxicity. Tumor endothelial cells may preferentially bind and internalize cationic liposomes.
A sodium salt form of cetaben, a unique, PPARalpha-independent peroxisome proliferator with hypolipidemic activity.
The fumarate salt of cevipabulin, a synthetic, water soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin, but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth., a small, water soluble, synthetic tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin, but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and may reduce cellular growth.
Sensitivity of a malignancy to administration of chemotherapy, usually defined as the achievement of a partial response or better.
An atypical teratoid/rhabdoid tumor occurring in children.
A small molecule Polo-like kinase 1 (PLK1) inhibitor with potential antineoplastic activity. Polo-like kinase 1 inhibitor GSK461364 selectively inhibits Plk1, inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner.
A polymeric prodrug of camptothecin (CPT) with potential antineoplastic activity. Polymeric camptothecin prodrug XMT-1001 consists of CPT conjugated to the 60-70 kDa, inert, bio-degradable, hydrophilic copolymer poly[1-hydroxymethylene hydroxymethyl formal] (PHF). Through a dual-phase, non-enzymatic release mechanism, CPT is first released in plasma from XMT-1001 as the lipophilic prodrugs CPT-SI (a succinimidoglycinate derivative) and CPT-SA (a succinamidoyl glycinate derivative), which are then hydrolyzed within tissues to release the lactone form of CPT. CPT inhibits the catalytic activity of DNA topoisomerase I, thereby inhibiting DNA replication and inducing apoptosis. This agent may exhibit a more favorable pharmacokinetic profile than other agents in the same class.
An orally bioavailable derivative of thalidomide with potential immunomodulating, antiangiogenic and antineoplastic activities. Although its exact mechanism of action has yet to be fully elucidated, pomalidomide appears to inhibit TNF-alpha production, enhance the activity of T cells and natural killer (NK) cells and enhance antibody-dependent cellular cytotoxicity (ADCC). In addition, pomalidomide may inhibit tumor angiogenesis, promote cell cycle arrest in susceptible tumor cell populations, and stimulate erythropoeisis.
A poorly differentiated squamous cell carcinoma arising from the salivary gland.
An oxazolidinone antibiotic agent with bactericidal activity against common gram-positive bacteria.
An adverse event that occurred after the patient had completed a clinical study (including any protocol-required post-treatment follow-up).
A disease status whereby the patient does not achieve a complete remission. It may not be limited to the first/initial course of therapy; it may represent all courses.
Disease status just prior to the start of the preparative regimen for hematopoietic stem cell transplantation (HSCT): Primary refractory refers to never achieving a complete remission (CR) from any therapy and also not being in partial remission (PR) at the time of the last evaluation prior to HSCT. PR could have been achieved at some point, but the recipient is no longer in PR.
Indicates that a person has received a degree allowing them to practice a profession, such as law, medicine, music, or ministry.
An orally bioavailable pentafluoroethyl derivative of a mifepristone-related steroid with antiprogestagenic activity. Lonaprisan is a pure, highly receptor-selective progesterone receptor (PR) antagonist; binding of this agent to PRs inhibits PR activation and the associated proliferative effects. Unlike many other antiprogestins such as mifepristone, this agent does not appear to convert to an agonist in the presence of protein kinase A (PKA) activators and shows high antiprogestagenic activity on both progesterone receptor (PR) isoforms PR-A and PR-B.
Progression of multiple myeloma or plasma cell leukemia requires any one or more of the following: Increase of 25% or more from baseline in: serum M-component with an absolute increase 0.5 g/dL or more (for progressive disease, serum M-component increases of 1 g/dL or more are sufficient to define relapse if the starting M component is 5 g/dL or more); urine M-component with an absolute increase 200 mg. or more/ 24 hours; for recipients without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase more than 10 mg/dL); bone marrow plasma cell percentage (absolute percentage 10% or more); definite development of new bone lesions or soft tissue plasmacytomas, or definite increase in the size of any existing bone lesions or soft tissue plasmacytomas; development of hypercalcemia (corrected serum calcium more than 11.5 mg/dL or 2.65 mmol) that can be attributed solely to the plasma cell proliferative disorder. Progression of disease requires two consecutive assessments made at any time before classification as disease progression, and/or the institution of any new therapy.
A cell-based vaccine derived from prostate cancer with potential immunopotentiating and antineoplastic activities. Prostate cancer vaccine ONY-P1 is derived from three irradiated allogeneic prostate cancer cell lines that represent different stages of prostate cancer and express a broad range of prostate and prostate cancer antigens. Upon administration, this vaccine may stimulate a host immune response against prostate cancer cells; in the vaccination schedule, the first two vaccinations are co-administered with bacillus Calmette-Guerin (BCG) as an adjuvant.
An imidazo-pyridine derivative with reversibly binding acid pump antagonist (APA) activity. Contrary to the mechanism of action of the proton pump inhibitors, which need to be activated by acid within the parietal cell canaliculus and which covalently react through the action of an active intermediate with the SH groups of the H+/K+-ATPase proton pump, pumaprazole competes reversibly with potassium binding on the extracytoplasmic face of the catalytic (alpha) subunit of the proton pump, immediately interrupting the pump's activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production.
A benzylpyridine with diuretic activity.
Corrected QT interval longer than 500 msec, in accordance with Bazett's correction formula.
An electrocardiographic finding of a corrected QT interval greater than 500 msec, in accordance with Fridericia's correction formula.
A fluoroquinolone derivative with antineoplastic activity. Quarfloxin disrupts the interaction between the nucleolin protein and a G-quadruplex DNA structure in the ribosomal DNA (rDNA) template, a critical interaction for rRNA biogenesis that is overexpressed in cancer cells; disruption of this G-quadruplex DNA:protein interaction in aberrant rRNA biogenesis may result in the inhibition of ribosome synthesis and tumor cell apoptosis.
An orally active, small molecule with potential antineoplastic activity. XL281 specifically inhibits RAF kinases, located downstream from RAS in the RAS/RAF/MEK/ERK kinase signaling pathway, which may result in reduced proliferation of tumor cells. RAS mutations may result in constitutive activation of the RAS/RAF/MEK/ERK kinase signaling pathway, and have been found to occur frequently in human tumors.
A grade III meningioma that occurs during adulthood.
A grade II meningioma that occurs during adulthood.
A grade I meningioma that occurs during adulthood.
A pure erythroid leukemia occurring in adults.
A supratentorial embryonal tumor, not otherwise specified that occurs in adults.
A classical Hodgkin lymphoma that occurs during childhood.
A grade III meningioma that occurs during childhood.
A grade II meningioma that occurs during childhood.
A grade I meningioma that occurs during childhood.
An uncommon hematologic malignancy occurring during childhood. Many of the morphologic, immunophenotypic, and genetic changes seen in adult myelodysplastic syndromes are also observed in the childhood variants of the disease. Children present with neutropenia and thrombocytopenia more often than adults, and bone marrow hypocellularity is more often seen in children than adults.
A mature or immature teratoma occurring in children.
Chromobox protein homolog 1 (185 aa, ~21 kDa) is encoded by the human CBX1 gene. This soluble, nuclear protein plays a role in epigenetic repression of chromatin and association of heterochromatin with the inner nuclear membrane.
The results of any chemical or enzymatic analyses of body fluids and tissues of an organism.
A vaginal lubricant formulated as a topical gel used to prevent and treat vaginal dryness. With a pH similar to that of normal vaginal discharge, Clino-San vaginal lubricant may reduce dryness, pain and irritation often caused by insufficient vaginal discharge due to atrophy of the vulvovaginal mucosa.
Cobalt ion requiring two electrons to return to its elemental state.
Complete response of multiple myeloma or plasma cell leukemia is characterized by negative immunofixation on serum and urine samples, and disappearance of any soft tissue plasmacytomas, and less than 5% plasma cells in the bone marrow (confirmation with repeat bone marrow biopsy not needed). Complete response requires two consecutive assessments made at any time before the institution of any new therapy, and no known evidence of progressive or new bone lesions if radiographic studies were performed; radiographic studies are not required to satisfy complete response requirements.
Problem associated with the deviations from documented system specifications that affects overall system performance and/or the performance of an individual medical device connected to that system.
The patient had achieved a complete response; received more therapy and continued in complete response.
A lipophilic copper(II)bis(thiosemicarbazone) labeled with the positron-emitting isotope (61)Cu with hypoxia-selective and radioisotopic activities. With a high membrane permeability and redox potential, (61)Cu-ATSM easily enters and selectively resides in hypoxic cells. The extent of (61)Cu-ATSM retention in tissue is inversely related to the state of tissue oxygenation allowing the quantitation of tissue hypoxia with positron emission tomography (PET).
A diagnostic radioimmunoconjugate comprised of the recombinant humanized monoclonal antibody trastuzumab conjugated with the positron-emitting radioisotope copper Cu 64. Copper Cu 64 trastuzumab binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2), allowing the detection of HER2 distribution using positron emission tomography (PET).
Problem associated with excessive radiation emitted from radiological or diagnostic devices.
Problem associated with too little radiation emitted from radiological or diagnostic devices.
A rationale for executing a plan of action.
A replication-deficient recombinant adenovirus encoding human interferon alpha-2b with potential antineoplastic activity. Upon intravesical administration, recombinant adenovirus-interferon SCH 721015 infects nearby tumor cells and expresses INF alpha-2b intracellularly which activates the transcription and translation of genes whose products mediate antiviral, antiproliferative, antitumor, and immune-modulating effects.
A peptide vaccine preparation, containing recombinant human epidermal growth factor (rEGF) linked to the Neisseria meningitidis-derived recombinant immunogenic carrier protein P64k (rP64k) and mixed with the immunoadjuvant Montanide ISA 51, with potential active immunotherapy activity. Recombinant human EGF-rP64K/Montanide ISA 51 vaccine may trigger a humoral immune response against vaccine rEGF and rP64K and, so, against endogenous EGF. Antibody-mediated inhibition of endogenous EGF binding to its receptor, epithelial growth factor receptor (EGFR), may result in the inhibition of tumor cell proliferation.
An 85-amino acid recombinant peptide derived from protein c2 of the hemophagocytic hookworm Ancylostoma caninum (a common canine parasite) with anticoagulant activity. Recombinant nematode anticoagulant protein c2 (rNAPc2) binds to circulating activated factor X (FXa) or zymogen factor X (FX) to form a binary complex which subsequently binds to and inhibits membrane-bound activated factor VII/tissue factor complex (FVIIa/TF). When administered prophylactically, this agent may reduce the incidence of deep venous thrombosis without hemostatic compromise. Because rNAPc2 inhibits the formation of the FVIIa/TF protease complex, which may play a role in the cellular signaling of both metastatic and angiogenic processes, it may impede tumor progression.
The reemergence of a spinal cord neoplasm in adulthood after a period of remission.
The reemergence of a central nervous system neoplasm after a period of remission.
The reemergence of a spinal cord neoplasm in childhood after a period of remission.
The reemergence of a spinal cord neoplasm after a period of remission.
Spinal cord neoplasm in adulthood which is resistant to treatment.
A central nervous system neoplasm resistant to treatment.
Spinal cord neoplasm in childhood which is resistant to treatment.
Spinal cord neoplasm resistant to treatment.
Relapse from complete response of multiple myeloma or plasma cell leukemia requires one or more of the following: reappearance of serum or urine M-protein by immunofixation or electrophoresis; development of 5% or more plasma cells in the bone marrow (relapse from complete response has a 5% cutoff vs.10% for other categories of relapse); appearance of any other sign of progression (e.g., new plasmacytoma, lytic bone lesion, hypercalcemia). Relapse requires two consecutive assessments made at any time before classification as relapse, and/or the institution of any new therapy.
A multipeptide cancer vaccine targeting renal cell carcinoma with potential immunopotentiating activity. Renal cell carcinoma peptides vaccine IMA901 consists of 10 different synthetic tumor-associated peptide (TUMAP) antigens (9 HLA-class I-binding and 1 HLA class II-binding); endogenously, these TUMAPs are expressed by the majority of renal cell carcinomas. Vaccination with this agent may significantly increase host cytotoxic T-lymphocyte (CTL) immune responses against tumor cells expressing these peptide antigens.
The hydrochloride salt form of a lipophilic, weak base with potassium-competitive acid blocking (P-CAB) activity. Revaprazan concentrates highly in the gastric parietal cell canaliculus and on entering this acidic environment is instantly protonated and binds competitively and reversibly to the potassium binding site of the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting the pump's activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production.
An electrocardiographic finding of ventricular tachycardia originating in the right ventricular outflow tract.
A purine nucleoside prodrug with activity against herpes simplex virus 1. In vivo, Rociclovir is converted to ganciclovir, which is further modified to its triphosphate form and inhibits viral DNA replication by competitive inhibition of viral DNA polymerases and incorporation into viral DNA, resulting in eventual termination of viral DNA elongation.
A tumor of the central nervous system that has components of both neurocytic and glial areas, whereby usually the glial component of the tumour predominates. Rossette-forming glioneuronal tumors (RGNT) have biphasic cytoarchitecture with two elements; neurocytic rosettes resembling Homer-Wright rosettes, and astrocytic component resembling a pilocytic astrocytoma. RGNTs are low-grade tumors that lack histopathological signs of malignancy.
The disulfate salt of the stable p-toluene-sulfonate complex of s-adenosyl-L-methionine (SAMe) with chemopreventive activity. SAMe disulfate p-toluene-sulfonate undergoes hydrolytic conversion to its active compound SAMe within cells. Although the mechanism of action is largely unknown, SAMe attenuates experimental liver damage and prevents experimental hepatocarcinogenesis. In addition, SAMe may reduce mitochondrial cytochrome C release, caspase 3 activation, and poly(ADP-ribose) polymerase cleavage, and attenuate okadaic acid-mediated hepatocyte apoptosis in a dose-dependent manner. SAMe is an essential compound in cellular transmethylation reactions and a precursor of polyamine and glutathione synthesis in the liver; SAMe deficiency is associated with chronic liver disease-associated decreases in the activity of methionine adenosyltransferase 1A (MAT1A), the enzyme that catalyzes the production of SAMe as the first step in methionine catabolism.
A tamoxifen metabolite with both estrogenic and anti-estrogenic effects. Afimoxifene has a higher affinity for the estrogen receptor than tamoxifen, and functions as an antagonist in breast cancer cells.
A proprietary oral formulation of D-methionine with antioxidant and antimucositis activities. D-methionine formulation MRX-1024 may selectively protect the oral mucosa from the toxic effects of chemotherapy and radiation therapy without compromising antitumor activity. D-methionine may be converted into the L- isomer in vivo, particularly in instances of L-methionine deprivation; both isomers have antioxidant activity which may be due, in part, to their sulfur moieties and chelating properties. L-methionine, an essential amino acid, also may help to maintain the ratio of reduced glutathione to oxidized glutathione in cells undergoing oxidative stress and may provide a source of L-cysteine for glutathione synthesis.
A cell-based vaccine composed of allogeneic dendritic cells (DC), pulsed with patient-specific non-Hodgkin's lymphoma idiotype (Id) determinants conjugated to keyhole limpet hemocyanin (KLH), with potential antitumor activity. Upon administration, this vaccine may stimulate the host immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against Id-expressing lymphoma cells, resulting in tumor cell lysis.
An autologous, multivalent dendritic cell vaccine targeting ovarian cancer with potential immunostimulating and antineoplastic activities. DC-OVA vaccine is produced in vitro by pulsing autologous dendritic cells with killed autologous primary ovarian tumors as a source of tumor-associated antigens (TAAs); the pulsed DCs are then matured using various cytokines. Upon administration, DC-OVA vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against ovarian cancer TAA-expressing ovarian cancer cells.
Patients with the X-linked hyper IgM syndrome have a deficiency of a protein, CD40 ligand that is found on the surface of T-lymphocytes. As a consequence of the deficiency of this protein, their T-lymphocytes are unable to instruct B-lymphocytes to switch their production of gamma globulins from IgM to IgG and IgA. As a result, patients have decreased levels of IgG and IgA and normal or elevated levels of IgM. In addition, since CD40 ligand is important to other functions of T-lymphocytes, they also have a defect in some of the protective functions of their T-lymphocytes.
A cancer vaccine containing HLA-A*2402-restricted epitopes derived from DEP domain containing 1 (DEPDC1) and M phase phosphoprotein 1 (MPHOSPH1) with potential immunostimulatory and antineoplastic activities. Upon administration, DEPDC1/MPHOSH1 peptide vaccine may elicit a specific cytotoxic T lymphocyte (CTL) response against tumor cells expressing DEPDC1 and MPHOSPH1, tumor antigens that are overexpressed in bladder cancer cells.
A THROMBIN inhibitor which acts by binding and blocking thrombogenic activity and the prevention of thrombus formation. It is used to reduce the risk of stroke and systemic EMBOLISM in patients with nonvalvular atrial fibrillation.
A substituted pyrimidone with inhibitory activity towards lipoprotein-associated phospholipase-A2 (Lp-PLA2), an important regulator of lipid metabolism and inflammation that circulates with lipoprotein particles and is carried into the arterial wall with low-density lipoprotein particles during the progression of atherosclerosis.
The hydrochloride salt of delapril, a lipophilic, non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, delapril is converted to two active metabolites, delapril diacid and 5-hydroxy delapril diacid, which competitively bind to and inhibit ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Delapril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
The tosylate salt form of denagliptin, a potent, selective, orally bioavailable, fluoropyrrolidine-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity.
The hydrochloride salt of denibulin, a small molecular vascular disrupting agent, with potential antimitotic and antineoplastic activities. Denibulin selectively targets and reversibly binds to the colchicine-binding site on tubulin and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells, ultimately leading to cell cycle arrest, blockage of cell division and apoptosis. This causes inadequate blood flow to the tumor and eventually leads to a decrease in tumor cell proliferation., a small molecule vascular disrupting agent (VDA), with potential antimitotic and antineoplastic activity. Denibulin selectively targets and reversibly binds to the colchicine-binding site on tubulin and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells (EC), ultimately leading to cell cycle arrest, blockage of cell division and apoptosis. This causes inadequate blood flow to the tumor and eventually leads to a decrease in tumor cell proliferation.
Arthritis associated with the destruction of the cartilage and the articular surface of the bone of the joint. This process severely interferes with movement in the joint.
Problem associated with environmental condition that results in the unsafe use of the device. (e.g. electromagnetic fields, noise, vibration, microbiological contamination etc.).
A formulation consisting of polymeric micelles loaded with the irinotecan metabolite SN-38 with potential antineoplastic activity. SN-38-loaded polymeric micelles NK012 is an SN-38-releasing nanodevice constructed by covalently attaching SN-38 to the block copolymer PEG-PGlu, followed by self-assembly of amphiphilic block copolymers in an aqueous milieu. SN-38 (7-ethyl-10-hydroxy-camptothecin), a biological active metabolite of the prodrug irinotecan (CPT-11), binds to and inhibits topoisomerase I by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication, and apoptosis. SN-38 has been reported to exhibit up to 1,000-fold more cytotoxic activity against various cancer cells in vitro than irinotecan. This formulation increases the water-solubility of SN-38 and allows the delivery of higher doses of SN-38 than those achievable with SN-38 alone.
An antimitotic tubulin-binding agent with potential antineoplastic activity. Tubulin-binding agent SSR97225 binds to tubulin, arresting the cell cycle at the G2/M checkpoint and preventing mitosis.
An electrocardiographic finding of ST elevation which is concave upwards, and which is often accompanied by PR segment depression. (CDISC)
An electrocardiographic finding of ST segment elevation or depression.
An oral absorption promoter. Salcaprozic acid may be used as a delivery agent to promote the oral absorption of certain macromolecules with poor bioavailability such as the peptides insulin and heparin.
An oral tablet containing an extract of the plant Salvia officinalis (common sage) with reported antihydrotic, antibiotic, antihypertensive, anti-inflammatory, antioxidant, astringent, antispasmodic, estrogenic, and hypoglycemic properties. The primary biologically active component of common sage appears to be its essential oil which contains mainly cineol, borneol, and alpha- and beta-thujone. In addition, sage leaf contains numerous other substances including tannic acid; resins with oleic, ursonic, and ursolic acids; bitter substances with cornsole and cornsolic acid; fumaric, chlorogenic, caffeic and nicotinic acids; nicotinamide; flavones; flavone glycosides; and estrogenic substances. However, the mechanism(s) of action of common sage in the treatment of various disorders is unclear.
The sodium salt form of sanfetrinem, an orally available tricyclic beta-lactam (trinem) antibiotic, with broad-spectrum activity against gram-positive and gram-negative bacteria. Sanfetrinem has high stability to many beta-lactamases.
A peptide with G2 checkpoint-abrogating activity. G2 checkpoint inhibitor CBP501 inhibits multiple serine/threonine kinases, including MAPKAP-K2, C-Tak1, and CHK1, that phosphorylate serine 216 of the dual-specific phosphatase Cdc25C (cell division checkpoint 25 C); disruption of Cdc25C activity results in the inhibition of Cdc25C dephosphorylation of the mitotic cyclin-dependent kinase complex Cdc2/cyclin B, preventing entry into the mitotic phase of the cell cycle.
A selective, orally active small molecule, targeting protein kinase B (PKB or AKT) and ribosomal protein S6 Kinase (p70S6K), with potential antineoplastic activity. XL418 inhibits the activities of PKB and p70S6K, both acting downstream of phosphoinosotide-3 kinase (PI3K). These kinases are often upregulated in a variety of cancers. Inhibition of PKB by this agent will induce apoptosis, while inhibition of p70S6K will result in the inhibition of translation within tumor cells.
Short QT syndrome is a condition that can cause a disruption of the heart's normal rhythm (arrhythmia). In people with this condition, the heart (cardiac) muscle takes less time than usual to recharge between beats. The term ""short QT"" refers to a specific pattern of heart activity that is detected with an electrocardiogram (EKG), which is a test used to measure the electrical activity of the heart. In people with this condition, the part of the heartbeat known as the QT interval is abnormally short.If untreated, the arrhythmia associated with short QT syndrome can lead to a variety of signs and symptoms, from dizziness and fainting (syncope) to cardiac arrest and sudden death. These signs and symptoms can occur any time from early infancy to old age. This condition may explain some cases of sudden infant death syndrome (SIDS), which is a major cause of unexplained death in babies younger than 1 year. However, some people with short QT syndrome never experience any health problems associated with the condition.
A tetrazene derivative with carcinostatic activity, but lacks measurable bone marrow destruction in animal models.
A low-grade papillary epithelial neoplasm (adenocarcinoma) with a slow growth pattern. The endolymphatic duct emerges from the posterior wall of the saccule (of the inner ear) and ends in a blind pouch, the endolymphatic sac. Endolymphatic sac tumors (ELSTs) are known under different names in the literature (Heffner tumor, aggressive papillary middle ear tumor, and low-grade adenocarcinoma of endolymphatic sac origin).
Any substance that inhibits aldehyde reductase (aldose reductase), an enzyme that participates in glucose metabolism and osmoregulation. Aldehyde reductase has been implicated in inflammatory disorders and diabetic complications.
A dual peroxisome proliferator-activated receptor (PPAR) agonist, with hypoglycemic activity. Aleglitazar binds to both PPARalpha and PPARgamma and decreases plasma levels of glucose, LDL-C, triglycerides (TG) and increases HDL levels. This agent may be used for the treatment of diabetes and cardiovascular disease.
The R-isomer of lansoprazole and a substituted benzimidazole prodrug with selective and irreversible proton pump inhibitor activity. As a weak base, dexlansoprazole accumulates in the acidic environment of the secretory canaliculus of the gastric parietal cell where it is converted to an active sulfenamide form that binds to cysteine sulfhydryl groups on the luminal aspect of the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting the pump's activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production.
A gel formulation of the sodium salt of diclofenac, a nonsteroidal benzeneacetic acid derivative with analgesic, antipyretic and anti-inflammatory activities. Diclofenac binds to and chelates both isoforms of cyclooxygenase (COX-1 and-2), thereby blocking the conversion of arachidonic acid (AA) to pro-inflammatory prostaglandins. This agent may also inhibit lipoxygenases, resulting in the inhibition of pro-inflammatory leukotriene synthesis from AA.
A polyunsaturated very long-chain fatty acid with a 22-carbon backbone and 6 double bonds, originating from the 3rd, 6th, 9th, 12th, 15th and 18th positions from the methyl end.
A highly purified solution of recombinant human deoxyribonuclease I (rhDNAse) with selective DNA cleaving activity. Administrated through inhalation of the nebulized solution, dornase alpha catalyzes DNA degradation in viscous airway secretions, which may render airway secretions less viscous, thus promoting the clearing of airway mucous plugging and improvement in pulmonary function.
A compound drug containing doxorubicin as an active ingredient.
An electrocardiographic finding which comprises left, right or bilateral atrial enlargement. This is may be characterized by prolonged P wave duration, increased P wave amplitude, or multi-component P waves. (CDISC)
An electrocardiographic finding suggesting an infarction in the anatomic location of the cardiac septum.
An electrocardiographic finding of a rhythm originating above the ventricles at a site other than the sinoatrial node.
An electrocardiographic finding of three or more consecutive complexes of ventricular origin. The QRS complexes are wide and have an abnormal morphology. (CDISC)
The sodium salt form of edaglitazone, an agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic activity. Edaglitazone also appears to lower triglyceride and free fatty acid levels.
The sodium salt form of efaproxiral, a propanoic acid and allosteric modifier of hemoglobin, with radiosensitizing activity. Efaproxiral binds non-covalently to the hemoglobin tetramer, thereby decreasing hemoglobin-oxygen binding affinity. This results in an increase in oxygen levels in hypoxic tumor tissues; increasing tumor oxygenation reduces tumor radioresistance.
A monounsaturated long-chain fatty acid with a 20-carbon backbone and the sole double bond originating from the 5th, 6th, 7th, 9th, 11th 12th or 15th positions from the methyl end.
An orally bioavailable small molecule Src kinase inhibitor with potential antineoplastic activity. Unlike other Src kinase inhibitors which bind to the ATP-binding site, Src kinase inhibitor KX2-391 specifically binds to the peptide substrate binding site of Src kinase; inhibition of kinase activity may result in the inhibition of primary tumor growth and the suppression of metastasis. Src tyrosine kinases are upregulated in many tumor cells and play important roles in tumor cell proliferation and metastasis.
Stable multiple myeloma or plasma cell leukemia is characterized by not meeting the criteria for complete response, very good partial response, partial response or progression of disease. Stable disease requires two consecutive assessments made at any time before the institution of any new therapy, and no known evidence of progressive or new bone lesions if radiographic studies were performed; radiographic studies are not required to satisfy stable disease requirements.
An allogeneic whole cell vaccine, derived from irradiated allogenic tumor cells manipulated to express human B7.1 (CD80 antigen) and human leukocyte antigen (HLA) A1, with potential antitumor activity. Vaccination with allogeneic B7.1/HLA-A1 transfected tumor cell vaccine may elicit a cytotoxic T lymphocyte (CTL) response against similar host tumor cells, resulting in decreased tumor cell proliferation.
A highly selective peptide agonist of the endothelin-B receptor. Endothelin B receptor agonist SPI-1620 binds to endothelin-B receptors on endothelial cells in tumor blood vessels, which, unlike the angioarchitecture of normal blood vessels, are relatively devoid of smooth muscle. This agent may induce a transient, selective increase in blood flow to a tumor, which may result in an increase in the delivery of anticancer agents to the tumor and, so, an increase in anticancer agent efficacy.
The sodium salt form of englitazone, an agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic activity. Englitazone also appears to decrease triacylglycerol levels in animal studies.
A shrub native to China and India. The stems and roots are used in traditional medicine as a diuretic and for asthma, bronchitis, and cough. It has also been promoted as a decongestant, a weight loss aid, and as a supplement to increase energy. Ephedra may cause high blood pressure, increased heart rate, or death if used with certain drugs, and may reduce the effects of certain drugs used to treat cancer and other diseases. The U.S. Food and Drug Administration has banned the sale of dietary supplements that contain ephedra. The scientific name is Ephedra sinica.
A structural analogue of erastin with potential antineoplastic activity. Erastin analogue PRLX 93936 appears to inhibit mitochondrial outer membrane protein VDACs (voltage-dependent anion channels) 2 and 3, resulting in an oxidative, non-apoptotic cell death. Erastin analogue PRLX 93936 exhibits greater lethality in cell lines harboring mutations in the GTPase protein oncogenes HRAS and KRAS or the serine-threonine protein kinase oncogene BRAF than in non-tumorigenic cell lines. VDACs 2 and 3 are up-regulated in a wide variety of tumor cell lines.
The chloride salt form of esoxybutynin, the dextrorotary form of oxybutynin S isomer [S(+)-isomer], with antispasmodic activity. Esoxybutynin chloride exerts its antimuscarinic effect on bladder smooth muscle by blocking muscarinic receptors in smooth muscle, thereby inhibiting acetylcholine binding. This results in a relaxation of bladder smooth muscle, a reduction of involuntary muscle contractions and delays the initial desire to void.
A genetic abnormality that arises from duplications of the juxtamembrane portion of the gene and results in constitutive activation of the FLT3 receptor tyrosine kinase protein in early hematopoietic progenitor cells. It is associated with acute myelogenous leukemia where it appears to correlate with a poor prognosis.
Single nucleotide mutations in the tyrosine kinase domain encoded by the human FLT3 gene that are associated with acute myeloid leukemia and poor prognosis.
An electrocardiographic finding of relatively short duration QRS complexes that originate from the region of the posterior fascicle (or occasionally the anterior fascicle) of the left bundle branch.
Indicates whether a specimen obtained from a subject that has abstained from food and possibly water for the prescribed amount of time; or from a subject who has not abstained from food or water.
A standardized freeze-dried preparation of desiccated table grapes containing polyphenols (including flavanols, anthocyanins, flavonols, and stilbenes such as resveratrol) and other unidentified compounds with antioxidant activity. Standardized freeze-dried table grape powder increases serum antioxidant activity and reduces the macrophage-mediated oxidation and uptake of low-density lipoprotein (LDL). This agent has been shown to inhibit genes linked to the development of sporadic colorectal cancer and may exhibit chemopreventive activity for other human cancers.
Stringent complete response (sCR) of multiple myeloma or plasma cell leukemia is characterized by complete response plus: normal free light chain ratio, and absence of clonal cells in the bone marrow by immunohistochemistry or immunofluorescence (confirmation with repeat bone marrow biopsy not needed). (Presence and/or absence of clonal cells is based upon the kappa/lambda ratio. An abnormal kappa/lambda ratio by immunohistochemistry and/or immunofluorescence requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting the presence of an abnormal clone is kappa/lambda of > 4:1 or < 1:2.). Stringent complete response requires two consecutive assessments made at any time before the institution of any new therapy, and no known evidence of progressive or new bone lesions if radiographic studies were performed; radiographic studies are not required to satisfy stringent complete response requirements.
A reason, motivation, or rationale for the activity-instance, such as the patient condition demands an intervention, or a patient requests that a procedure be performed.
A sulfonamide antibiotic used in the treatment of leprosy.
A sulfamoylbenzoic acid derivative with diuretic activity. Compared to its sulfamoyl analogue clofenamide, sulclamide is a more potent diuretic and a less active carbonic anhydrase inhibitor.
A long-acting sulfonamide antibiotic with antipyretic properties.
A sodium salft form of sulfapyridine, a sulfonamide antibiotic and by product of sulfasalazine.
A sulfonamide derivative belonging to the class of the thiazide diuretics with anti-hypertensive activity. Sumetizide was never marketed.
A modified recombinant nonapeptide (LMLGEFLKL) derived from the anti-apoptosis protein survivin with potential immunopotentiating and antineoplastic activities. Upon administration, survivin Sur1M2 peptide vaccine may elicit humoral and cellular immune responses against survivin-expressing cancers, resulting in decreased tumor cell proliferation and tumor cell death. The survivin protein inhibits caspase activation and apoptosis; it is undetectable in normal adult tissues but is expressed by several human cancers including lung, colon, breast, pancreas, and prostate cancer as well as hematopoietic malignancies and skin cancers.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with synthetic brain tumor peptides with potential immunostimulatory and antineoplastic activities. Upon administration, synthetic brain tumor peptides-pulsed autologous dendritic cell vaccine may stimulate anti-tumoral cytotoxic T lymphocyte (CTL)l and antibody responses against glioma tumor cells, resulting in glioma tumor cell lysis.
A proprietary oligonucleotide with immunostimulatory activity. Immunostimulatory phosphorothiolate oligodeoxyribonucleotide SD-101 targets Toll-Like Receptor 9 (TLR9) found on a specialized subset of dendritic cells. The interaction of TLR9 with SD-101, in conjunction with an allergen or antigen, induces activation of memory T helper cells 1 (Th1) against a specific pathogen or allergen, thereby leading to long-lasting therapeutic effects. Furthermore, this agent does not cause a generalized activation of the immune system.
An electrocardiographic finding of a T wave with both positive and negative components. (CDISC)
An electrocardiographic finding in which the T wave appears decreased in amplitude.
A malignant germ cell tumor arising from the testis. It is characterized by a mixture of choriocarcinoma and yolk sac tumor morphologic elements. Patients may present with painless or painful testicular swelling.
The result of the investigation of the absorption, distribution, metabolism, and excretion (ADME) of an experimental substance by an organism.
A fermented soybean-derived phytochemical beverage with potential antineoplastic activity. Fermented soybean protein beverage is reported to exhibit immunostimulatory, anti-viral, pro-apoptotic, anti-angiogenic, anti-proliferative, and anti-inflammatory activities and to enhance the cytotoxic effects of natural killer (NK) cells. The fermentation process is reported to hydrolyze many soybean proteins into amino acids and nitrogen-rich compounds and to protect and enhance the activities of isoflavones such as genistein, protease inhibitors, saponins, phytosterols, inositol hexaphosphate, and other beneficial dietary nutrients and micronutrients found in soybeans.
A 2-nitroimidazole labeled with the positron-emitting radioisotope fluorine F 18. HX4, the 2-nitroimidazole moiety of [F-18]HX4, is selectively bioreduced and bound in hypoxic tumor cells, permitting the imaging of hypoxic tumor cells with positron emission tomography (PET).
A combination preparation of the fumarate salt of a beta2-adrenergic receptor agonist and a macrolide antibiotic, with muscle-sparing and anti-cachexia effects. Formoterol appears to antagonize cachexia by reducing proteolysis mediated through the ubiquitin-protease pathway. Roxithromycin strongly inhibits inflammatory cytokine production and secretion from T cells and macrophages in vitro and in vivo. The combination exhibits a greater muscle sparing effect than either drug given individually at comparable doses.
A cancer vaccine, containing epitopes of the gangliosides GD2 and GD3 conjugated with the immunostimulant keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. Vaccination with GD2 lactone/GD3 lactone-KLH conjugate bivalent vaccine may elicit antibodies against tumor cells expressing either epitope, resulting in complement-mediated cytotoxicity (CMC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Located primarily in the nervous system, gangliosides, such as GD2 and GD3, are cell membrane components involved in cellular recognition and cell-cell communication.
An adenovirus encoding an endothelial cell-specific, murine pre-proendothelin-1 (PPE-1) promoter and a Fas-based chimeric death receptor with potential anti-angiogenic activity. Endothelial cell-specific transcriptional control of the adenoviral vector is achieved by the use of a modified murine PPE-1 promoter that is specifically activated in PPE-1-expressing angiogenic endothelial cells residing in the tumor microvasculature. Subsequently, the Fas-c (Fas-chimeric) death receptor, containing Fas and tumor necrosis factor (TNF) receptor 1 (TNFR1) moieties, is expressed in angiogenic endothelial cells; endothelial cell-specific Fas-mediated apoptosis is initiated by the binding of TNF-alpha, abundant in the tumor microenvironment, to the TNFR1 moiety of the expressed Fas-c death receptor.
An undifferentiated carcinoma that arises from the gallbladder. It is characterized by the presence of spindle and giant malignant cells, including osteoclast-like giant cells.
A gallium Ga 68-radiolabeled analogue of somatostatin that may be used in conjunction with positron emission tomography (PET) to image neuroendocrine tumors and metastases. Gallium Ga 68-DOTANOC is a conjugate of the somatostatin analogue Nal3-octreotide (NOC) and gallium Ga 68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). The somatostatin analogue NOC has a high affinity for somatostatin receptor subtypes 2, 3, and 5; these receptor subtypes have been shown to be present in large numbers on neuroendocrine tumors and their metastases, while most other normal tissues express low levels of these somatostatin receptor subtypes.
A radioimmunoconjugate consisting of a trastuzumab fragment labeled with the positron-emitting radioisotope gallium Ga 68 with radioisotopic and antibody activities. Upon administration, Ga-68-labeled F(ab')2-trastuzumab may bind to HER2-positive tumor cells, allowing radioimmunolocalization with positron emission tomography (PET). Trastuzumab is a recombinant humanized monoclonal antibody that selectively binds to the extracellular domain of human epidermal growth factor receptor 2 (HER2), overexpressed by many adenocarcinomas, particularly breast adenocarcinomas.
An orally available 5-fluorouracil (5-FU) prodrug with potential antineoplastic activity. Upon administration, galocitabine is converted into 5'-deoxy-5-fluorocytidine, 5'-deoxy-fluorouridine, and 5-FU. 5-FU is further metabolized into other cytotoxic metabolites that interfere with RNA and DNA synthesis via inhibition of thymidylate synthase. As a result, this agent eventually inhibits tumor cell growth.
An adenocarcinoma that arises from the gastric mucosa and is characterized by the presence of both glandular and poorly cohesive malignant cellular components.
A synthetic steroid similar or identical to endogenous estetrol, a short-acting estrogen with both agonistic and antagonistic estrogen receptor activity. Administered orally, therapeutic estetrol binds to the estrogen receptor and as a selective estrogen receptor modulator (SERM) exhibits estrogen agonism in certain tissues and estrogen antagonism in others. Displaying weak estrogen activity in the uterus, estetrol acts as an estrogen antagonist in breast tissue. Produced solely by the human fetal liver, endogenous estetrol is the primary estrogen metabolite of estrogen biosynthesis in the human fetal liver.
A sterile, lyophilized powder of hemin, the Fe3+ oxidation product of heme (Fe2+), derived from processed red blood cells. Therapeutic hemin appears to inhibit delta-aminolevulinic acid (ALA) synthetase, a rate-limiting enzyme in the porphyrin/heme biosynthetic pathway, resulting in inhibition of the hepatic and/or marrow synthesis of porphyrin precursors. The mechanism by which therapeutic hematin produces symptomatic improvement in patients with acute episodes of the hepatic porphyrias has not been determined.
A first-generation, cyclohexyl-containing sulfonylurea with antihyperglycemic activity. Thiohexamide has never been marketed.
An oncolytic thymidine kinase (TK)-deleted vaccinia poxvirus expressing human GM-CSF (hGM-CSF) with antineoplastic activity. Upon intratumoral or intravenous administration, pexastimogene devacirepvec selectively infects and lyses tumor cells. While vaccinia displays a natural tumor cell tropism, deletion of the TK gene increases the tumor selectivity of vaccinia by limiting viral replication to cells expressing high levels of TK, such as certain cancer cells. hGM-CSF expression by this agent helps recruit antigen presenting cells (APCs), such as dendritic cells (DCs) and macrophages, to virally infected tumor cells, thereby initiating an antitumoral immune response.
A first-generation cyclopentyl-containing sulfonylurea with hypoglycemic activity. Tolpentamide was never marketed.
A sulfonamide derivative with hypoglycemic activity.
A topical preparation of gemcitabine hydrochloride with antineoplastic activity. Gemcitabine, an analogue of the antimetabolite nucleoside deoxycytidine, is converted intracellularly to the active metabolites difluorodeoxycytidine di- and triphosphate (dFdCDP, dFdCTP). dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and apoptosis.
The results of any analysis that determine the toxicity of a chemical compound.
Triple-negative breast cancer finding is a negative test result that occurs when the cells in the tumor of a breast cancer patient lack the receptors for both estrogen and progesterone and the human epidermal growth factor receptor 2.
A synthetic molecule that targets multiple tyrosine kinases with potential antineoplastic activity. Tyrosine kinase inhibitor XL228 binds to and inhibits the activities of multiple tyrosine kinases, such as the insulin-like growth factor 1 receptor (IGF1R), Src tyrosine kinase, and Bcr-Abl tyrosine kinase. Blockade of these kinases may result in the inhibition of tumor angiogenesis, cell proliferation, and metastasis. In addition, this agent may be a potent inhibitor of the T315I mutant form of the Abl protein, which is associated with the resistance of chronic myelogenous leukemia (CML) to other tyrosine kinase inhibitors. IGF1R and Src tyrosine kinases are upregulated in many tumor cells and play important roles in tumor cell proliferation and metastasis. Bcr-Abl translocation leads to constitutive activation of ABL kinase and is commonly associated with Philadelphia-positive acute lymphocytic leukemia (ALL).
A cancer vaccine containing five peptide epitopes with potential immunostimulatory and antitumor activity. Peptide epitopes in this vaccine are derived from: URLC10 (up-regulated lung cancer 10), TTK (TTK protein kinase), KOC1 (IGF II mRNA Binding Protein 3) and VEGFRs (vascular endothelial growth factor receptors) 1 and 2. Upon administration, URLC10-TTK-KOC1-VEGFR1-VEGFR2 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing URLC10, TTK, KCO1, VEGFR 1 and 2 peptides, resulting in cell lysis and decreased tumor growth.
A cancer vaccine containing URLC10 (up-regulated lung cancer 10) epitopes with potential immunostimulatory and antineoplastic activities. Upon administration, URL peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against URLC10-expressing tumor cells. Up-regulated in lung and esophageal cancers, the function of URLC10 is unknown.
A cancer vaccine containing a replication-defective recombinant canarypox virus (ALVAC), encoding an epitope of MART-1 (melanoma antigen recognized by T-cells), with potential immunostimulatory and antineoplastic activities. Upon administration, the MART-1 epitope is expressed by the ALVAC vector in ALVAC-MART-1 vaccine; a host cytotoxic T lymphocyte (CTL) response against MART-1-expressing tumor cells may follow, resulting in tumor cell lysis and decreased tumor cell proliferation.
A therapeutic cancer vaccine, based on a replication-defective recombinant canarypox virus (ALVAC) encoding multiple melanoma antigens, with potential immunostimulatory and antineoplastic activities. Vaccination with ALVAC(2) melanoma multi-antigen therapeutic vaccine may stimulate the host immune system to mount an immune response against antigen-expressing melanoma cells, resulting in inhibition of tumor growth and/or metastasis.
A cancer vaccine consisting of autologous dendritic cells loaded with separate preparations of acute myelogenous leukemia (AML) cell lysate and AML-specific messenger RNA (mRNA) with potential immunostimulatory and antineoplastic activities. Upon administration, AML mRNA plus lysate loaded autologous dendritic cell vaccine may elicit a potent cytotoxic T-cell (CTL) response against AML cells, resulting in tumor cell death. Autologous dendritic cells doubly-loaded with AML cell lysate and AML-specific mRNA may elicit superior primary, recall, and effector lytic immune responses compared to autologous dendritic cells loaded with tumor lysate or tumor mRNA alone.
A sulfonamide derivative with antihyperglycemic activity. Glicetanile is both rapidly metabolized and eliminated via urine and faeces after oral and i.v. administration, thereby preventing adverse hypoglycemic effects.
The sodium salt form of glicetanile, a sulfonamide derivative with antihyperglycemic activity. Glicetanile is both rapidly metabolized and eliminated via urine and faeces after oral and i.v. administration, thereby preventing adverse hypoglycemic effects.
A sulfonamide derivative with antihyperglycemic activity. Like sulfonylureas, glicondamide is able to lower blood glucose levels by increasing the release of insulin from pancreatic beta cells.
A cancer vaccine comprised of autologous dendritic cells pulsed with synthetic glioma-associated antigen (GAA) peptides with potential antineoplastic activity. Upon administration, this vaccine may stimulate anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against GAA peptide-expressing glioma cells, resulting in tumor cell lysis.
A second-generation sulfonylurea with antihyperglycemic activity. Like other larger sulfonylurea compounds, glisamuride appears to exert greater binding affinity for peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic activity among most of the first and second-generation agents.
A second-generation sulfonylurea with antihyperglycemic activity. Like other second-generation compounds, glisindamide exerts greater binding affinity to sulfonylurea receptor type 1 (SUR1) than the first-generation compounds and shows peroxisome proliferator-activated receptor gamma (PPARgamma) agonistic activity.
A sulfonamide derivative with antihyperglycemic activity. Like sulfonylureas, glybuthiazol is able to lower blood glucose levels by increasing the release of insulin from pancreatic beta cells.
Biliary intraepithelial neoplasia characterized by the presence of mild epithelial atypia.
Biliary intraepithelial neoplasia characterized by the presence of moderate epithelial atypia.
Biliary intraepithelial neoplasia characterized by the presence of severe epithelial atypia.
The absence of detectable HER2/Neu in a tissue sample.
A laboratory test result indicating the presence of HLA-A*01 positive cells in a tissue sample.
A laboratory test result indicating the presence of HLA-A*24 positive cells in a tissue sample.
A laboratory test result indicating the presence of HLA-A*02 positive cells in a tissue sample.
A cancer vacine containing four HLA-A*2402-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from: URLC10 (up-regulated lung cancer 10), TTK (TTK protein kinase), and VEGFRs (vascular endothelial growth factor receptors) 1 and 2. Upon administration, URLC10-TTK-KOC1-VEGFR1-VEGFR2 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing URLC10, TTK, VEGFR 1 and 2 peptides, resulting in cell lysis and decreased tumor growth. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A preparation of allogeneic HLA-matched leukocytes treated with a derivative of placental protein 14 (PP14) with potential immunomodulating activity. PP14 derivative-treated HLA-matched donor mononuclear cell-enriched leukocytes contain at least fifty-five percent early-apoptotic T cells; after infusion and when processed by recipient dendritic cells, early-apoptotic T cells may help induce a decrease in the donor effector T-cell responses against the recipient of an allogeneic hematopoietic stem cell (HSC) transplant, thereby minimizing allogeneic HSC transplant-related graft-versus-host disease (GVHD). PP14, a 162 amino acid glycosylated protein secreted by the late secretory phase endometrium, binds to T cells in a carbohydrate fashion and has been shown to induce T-cell apoptosis; maternal immune tolerance to the fetus and pregnancy-related remissions of autoimmune disease may involve PP14-induced T cell apoptosis.
A description of heterogeneous density elements seen in a tissue composition image obtained by sonography.
A formulation of the mustard plant Brassica juncea grown in a medium that has been enriched with the trace element selenium with potential chemopreventive and chemopotentiating activities. Brassica juncea hyperaccumulates trace elements in soil. Selenium amino acid species found in selenized Brassica juncea include methylselenomethionine (MeSeMet) and methylselenocysteine (MeSeCys); both may be incorporated into selenoproteins in vivo. Selenium functions as a cofactor for antioxidant enzymes such as glutathione peroxidases and thioredoxin reductase, which protect cells from the free radical damage. In addition, in vitro MeSeCys has been shown to potentiate the antitumor effects of the irinotecan metabolite SN-38, by inducing phosphorylation of checkpoint kinase 2 (chk2) at threonine 68, which results in poly(ADP-ribose) polymerase cleavage, caspase 3 activation, and DNA fragmentation.
A description of homogeneous fat lobules seen in a tissue composition image obtained by sonography.
A description of homogeneous fibroglandular elements seen in a tissue composition image obtained by sonography.
An indication or description that an extended period of hospitalization is necessary.
An agent that targets the human heat-shock protein 90 (Hsp90) with potential antineoplastic activity. Although the mechanism of action remains to be fully elucidated, Hsp90 antagonist KW-2478 appears to inhibit Hsp90, resulting in impaired signal transduction, inhibition of cell proliferation, and the induction of apoptosis in tumor cells. HSP90 is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation or immune responses.
A derivative of 4,5-diarylisoxazole and a third-generation heat shock protein 90 (Hsp90) inhibitor with potential antineoplastic activity. Hsp90 inhibitor AUY922 has been shown to bind with high affinity to and inhibit Hsp90, resulting in the proteasomal degradation of oncogenic client proteins; the inhibition of cell proliferation; and the elevation of heat shock protein 72 (Hsp72) in a wide range of human tumor cell lines. Hsp90, a 90 kDa molecular chaperone, plays a key role in the conformational maturation, stability and function of other substrate or ""client"" proteins within the cell, many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, transcription factors and hormone receptors. Hsp72 exhibits anti-apoptotic functions; its up-regulation may be used as a surrogate marker for Hsp90 inhibition.
The orally bioavailable mesylate salt of a synthetic prodrug targeting the human heat-shock protein 90 (Hsp90) with potential antineoplastic activity. Although the mechanism of action remains to be fully elucidated, Hsp90 inhibitor SNX-5542 is rapidly converted to SNX-2112, which accumulates in tumors relative to normal tissues. SNX-2112 inhibits Hsp90, which may result in the proteasomal degradation of oncogenic client proteins, including HER2/ERBB2, and the inhibition of tumor cell proliferation. Hsp90 is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation or immune responses.
A vaccine formulation consisting of several types of human papillomavirus (HPV)-derived noninfectious virus-like particles (VLPs) with potential immunoprophylactic activity. Upon administration, HPV L1 VLP vaccine V504 may generate humoral immunity against various HPV L1 major capsid proteins, thereby preventing cervical infection upon exposure to the associated HPV types. VLPs are composed of self-assembling L1 major capsid proteins or functional L1 major capsid protein derivatives.
A vaccine consisting of noninfectious, recombinant virus-like particles (VLP) containing the major viral capsid protein L1 of nine strains of human papillomavirus (HPV), with potential immunoprotective activity. Vaccination with HPV V503 may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against cells positive for any of these nine strains of HPV, thereby preventing cervical infection upon exposure to certain HPV subtypes.
A thiadiazoline angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Utibaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Utibaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
The dihydrochloride salt of valopicitabine, a 3-O-valine ester prodrug form of the nucleoside analog 2'-C-methylcytidine with anti-hepatitis C virus (HCV) activity. Upon administration, valopicitabine is converted into 2'-C-methylcytidine; upon phosphorylation into its 5-triphosphate form, this metabolite inhibits viral RNA chain elongation and viral RNA-dependent RNA polymerase activity. This blocks viral production of HCV RNA and thus viral replication.
An intravenously administered inhibitor of secretory phospholipase A2 (sPLA2) with orphan drug designation. Varespladib is in trial for prevention of Acute Chest Syndrome in the treatment of sickle cell disease.
Difficulties related to an apparatus used to gain access to arteries and veins.
A proprietary conjugate of paclitaxel with antineoplastic activity. Similar to the free drug, the paclitaxel moiety in vector-peptide conjugated paclitaxel binds to and stabilizes tubulin molecules, promoting assembly of microtubules and inhibiting tubulin disassembly which results in the inhibition of cell division. The Kunitz domain-derived vector-peptide carries the conjugated paclitaxel through the blood brain barrier (BBB), bypassing the transmembrane p-glycoprotein (P-gp) efflux pump, which may result in higher concentrations of paclitaxel in the brain parenchyma.
An electrocardiographic finding of multiple, temporally related, episodes of ventricular tachycardia or fibrillation, occurring three or more times in a 24 hour period.
An electrocardiographic finding of a ventricular tachycardia that is terminated successfully with verapamil administration.
Very good partial response of multiple myeloma or plasma cell leukemia is characterized by serum and urine M-protein detectable by immunofixation but not on electrophoresis, or at least 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours. Very good partial response requires two consecutive assessments made at any time before the institution of any new therapy, and no known evidence of progressive or new bone lesions if radiographic studies were performed; radiographic studies are not required to satisfy very good partial response requirements.
A maleate salt form of Vicriviroc, a piperazine-based CCR5 receptor antagonist with activity against human immunodeficiency virus. Vicriviroc is designed to bind to CCR5 and inhibit the entry of HIV into CD4 cells.
A population of allogeneic T-cells sensitized with Wilms tumor 1 (WT1) antigen with potential immunostimulatory and antineoplastic activities. Upon administration, WT1-sensitized T cells may bind to and lyse WT1-expressing tumor cells. WT1 antigen, a zinc finger DNA-binding protein acting as a transcriptional activator or repressor depending on the cellular or chromosomal context, is overexpressed in leukemic cells and in a vast number of nonhematological solid tumors.
An adrenal cortex carcinoma characterized by the presence of morphologic and cytologic features reminiscent of the normal adrenal cortex and absence of sarcomatous or anaplastic features.
An electrocardiographic finding of three or more consecutive wide QRS complexes of uncertain origin with a rate greater than a certain threshold (100 or 120 beats per minute are commonly used). (CDISC)
A plasmid DNA vaccine, encoding an epitope of mouse tyrosinase, with potential antineoplastic activity. Administered via intramuscular electroporation, vaccination with xenogeneic tyrosinase DNA vaccine may induce both humoral and cytotoxic lymphocyte (CTL) immune responses against melanoma cells that express tyrosinase, resulting in decreased tumor growth.
A radioimmunoconjugate consisting of the murine IgG1 anti-CD19 monoclonal antibody (MoAb) BU12 labeled with the beta-emitting radioisotope yttrium Y 90 with radioisotopic and antibody activities. Yttrium Y 90 anti-CD19 monoclonal antibody BU12 binds to the CD19 molecule, specifically delivering cytotoxic beta radiation to CD19-expressing B cells. CD19 is a membrane antigen that is widely expressed during B-cell development, from pro-B-cell to early plasma cell stages.
A radioimmunoconjugate comprised of the monoclonal antibody AHN-12 conjugated to the radioisotope yttrium 90 with potential radioimmunotherapeutic activity. Yttrium Y 90 monoclonal antibody AHN-12 binds to the tyrosine phosphatase CD45, expressed on the surface of normal and malignant hematopoietic cells. After binding and internalization by CD45-expressing tumor cells, this agent may deliver a cytotoxic dose of beta radiation.
A unilateral headache of moderate intensity with exacerbations of severe pain, not attributed to another disorder, that continuously persists for more than three months, and presents with ipsilateral autonomic symptoms during exacerbations.
A bilateral, unremitting headache of mild to moderate intensity that occurs daily and may be associated with photophobia, phonophobia, or mild nausea.
Asymmetry between native breast and reconstructed breast.
Fever within the usual recovery period with the possibility that it is etiologically linked to the procedure and may indicate a complication.
Fever within the usual recovery period with the possibility that it is etiologically linked to the vaccination and may indicate a complication.
An electrocardiographic finding of a wide QRS complex with evidence of delayed conduction to the left ventricle, manifest as a widened initial portion of the QRS complex in leads V5, V6, I and aVL and with QRS duration less than 120 ms. (CDISC)
An electrocardiographic finding of a QRS amplitude less than or equal to 0.5 mV in the limb leads or QRS amplitude less than or equal to 1 mV in the precordial leads. (CDISC)
Carcinoma, predominantly squamous cell, arising from the epithelial cells of the oropharynx.
An attenuated strain of Mycobacterium w, a non-pathogenic, rapidly growing, atypical mycobacterium, with non-specific immunopotentiating properties. In addition to sharing a number of common B and T cell determinants with Mycobacterium leprae and Mycobacterium tuberculosis, Mycobacterium w (Mw) also shares an immunogenic determinant with prostate specific antigen (PSA). In vitro and in vivo studies have shown that heat-killed Mw can induce significant T-cell responses. This agent may induce host T-cell responses against tumor cells expressing PSA. PSA is a glycoprotein secreted by prostatic epithelial and ductal cells and may be overexpressed in prostate cancer cells.
A single lung lesion that is characterized by a small round mass of tissue, usually less than 1 cm in diameter, and can be detected by chest radiography. A solitary pulmonary nodule can be associated with neoplasm, tuberculosis, cyst, or other anomalies in the lung, the CHEST WALL, or the PLEURA.
The first region-restricted episode of CNS inflammatory demyelination in a patient. It is usually characterized by an acute monosymptomatic presentation of the optic nerves, brainstem, or spinal cord. It may not reoccur (isolated), or it may progress to MULTIPLE SCLEROSIS.
A type of developmental disturbance of AMELOGENESIS involving permanent INCISORS and first permanent MOLARS. It is characterized by asymmetrical enamel defects with severe hypomineralization.
A malignant neoplasm that affects the ear. Representative examples include ceruminous adenocarcinoma and squamous cell carcinoma of the external ear and adenocarcinoma of the middle ear.
A synthetic codeine analogue, Tramadol Hydrochloride has central analgesic properties with effects similar to opioids, such as morphine and codeine, acting on specific opioid receptors. The hydrochloride salt of Tramadol and used as a narcotic analgesic for severe pain, it can be addictive and weakly inhibits norepinephrine and serotonin reuptake. (NCI04)
A condition that is characterized by multiple sites of lymphoid infiltration, often with an aggressive, necrotizing lesion of the upper airway. The term was used as a synonym for lethal midline granuloma.
This type is characterized by a bulky solid mass with cysts of <0.5 cm.
This type is macrocystic, characterized by a single or multiple cysts of >2.5 cm.
This type is microcystic, characterized by multiple cysts of 0.5 to 2.5 cm.
An inherited condition characterized by multiple malformations of CARTILAGE and bone including CRANIOSYNOSTOSIS; midface hypoplasia; radiohumeral SYNOSTOSIS; CHOANAL ATRESIA; femoral bowing; neonatal fractures; and multiple joint CONTRACTURES and, occasionally, urogenital, gastrointestinal or cardiac defects. In utero exposure to FLUCONAZOLE, as well as mutations in at least two separate genes are associated with this condition - POR (encoding P450 (cytochrome) oxidoreductase (NADPH-FERRIHEMOPROTEIN REDUCTASE)) and FGFR2 (encoding FIBROBLAST GROWTH FACTOR RECEPTOR 2).
PEComas containing glycogen-rich clear cytoplasm and found in the lung and a wide range of extrapulmonary sites.
A group of interstitial lung diseases with no known etiology. There are several entities with varying patterns of inflammation and fibrosis. They are classified by their distinct clinical-radiological-pathological features and prognosis. They include IDIOPATHIC PULMONARY FIBROSIS; CRYPTOGENIC ORGANIZING PNEUMONIA; and others.
Bacterial vaccines prepared from non-pathogenic, autologous bacteria of human origin. In Eastern Europe they are used in humans to treat chronic inflammatory disorders that are resistant to standard treatments. Worldwide they have veterinary use in all types of infectious disease.
A degenerative joint disease involving the SPINE. It is characterized by progressive deterioration of the spinal articular cartilage (CARTILAGE, ARTICULAR), usually with hardening of the subchondral bone and outgrowth of bone spurs (OSTEOPHYTE).
Degradation or wasting of the PERIODONTIUM tissues that may involve the gum (GINGIVA), the alveolar bone (ALVEOLAR PROCESS), the DENTAL CEMENTUM, or the PERIODONTAL LIGAMENT.
Hydroxyethyl starch derivative with five hydroxyethyl groups.
An unexplained illness which is characterized by skin manifestations including non-healing lesions, itching, and the appearance of fibers.
An inflammatory disease and serious complication of PANCREAS TRANSPLANTATION. It is caused by a premature activation of pancreatic proenzymes leading to autodigestion of the gland and can be attributed to immunological or nonimmunological causes.
A rare form of myositis that affects only the orbital muscles.
Lipopeptides with an anionic peptide scaffold.
Lipopeptides with an cationic peptide scaffold.
Viscoelastic solutions that are injected into JOINTS in order to alleviate symptoms of joint-related disorders such as OSTEOARTHRITIS.
Infections of the respiratory tract with fungi of the genus ASPERGILLUS.
Historical remedies or medicinal preparations believed to have the power of invigorating or promoting restoration of tissues or the body.
A humanized monoclonal IgG1 antibody directed against the vitronectin receptor alpha v beta 3 integrin. Etaracizumab blocks the binding of ligands, such as vitronectin, to alpha v beta 3 integrin, resulting in inhibition of angiogenesis and metastasis. Alpha v beta 3 integrin is a cell adhesion and signaling receptor that is expressed on the surface of tumor vessel endothelial cells, some tumor cells, and a number of other cell types.
A peptidomimetic inhibitor with activity against human rhinoviruses. Rupintrivir is an irreversible 3C protease inhibitor which blocks processing of viral proteins, thus blocking viral replication.
The sodium salt form of the biologically inert, selective relaxant binding agent (SRBA) sugammadex, a modified, anionic gamma cyclodextrin derivative containing a hydrophilic exterior and a hydrophobic core, with neuromuscular blocking drug (NMBD) reversal activity. Upon administration, the negatively charged carboxyl-thio-ether groups of sugammadex selectively and reversibly bind to the positively charged quaternary nitrogen of a steroidal NMBD, which was administered at an earlier time for anesthetic purposes. The encapsulation of the NMBD by sugammadex blocks its ability to bind to nicotinic receptors in the neuromuscular junction and thereby reverses the NMBD-induced neuromuscular blockade. Sugammadex binds rocuronium, vecuronium, and to a lesser extent pancuronium.
An analogue of halichondrin B, a substance derived from a marine sponge (Lissodendoryx sp.) with antineoplastic activity. Eribulin binds to the vinca domain of tubulin and inhibits the polymerization of tubulin and the assembly of microtubules, resulting in inhibition of mitotic spindle assembly, induction of cell cycle arrest at G2/M phase, and, potentially, tumor regression.
Disease resulting from exposure to beryllium. Entry into the body is not limited to the inhalation route.
A form that is characterized by partial or complete obstruction of bronchiolar lumens resulting from chronic bronchiolar inflammation, scarring, and smooth muscle hypertrophy.
Pulmonary eosinophilia or pneumonia caused by parasitic infections in tropical areas .
A form that is histologically characterized by intraluminal polyps of organizing connective tissue.
A neurokinin receptor antagonist with antiemetic activity. This agent is approved for veterinary use only.
A human IgG2 monoclonal antibody directed against the T-cell receptor protein cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Tremelimumab binds to CTLA4 and blocks the binding of the antigen-presenting cell ligands B7-1 and B7-2 to CTLA4, resulting in inhibition of B7-CTLA4-mediated downregulation of T-cell activation; subsequently, B7-1 or B7-2 may interact with another T-cell surface receptor protein, CD28, resulting in a B7-CD28-mediated T-cell activation unopposed by B7-CTLA4-mediated inhibition.
A synthetic p-aminophenol derivative combined with codeine, with anti-inflammatory and analgesic activites. Acetaminophen with codeine is used against inflammatory conditions, fever, and pain. Codeine is an opium alkaloid with analgesic properties. Acetaminophen appears to inhibit prostaglandin biosynthesis in the central nervous system and less in peripheral tissues.
A water soluble, small-molecule prodrug containing the pan-PI3K/mTOR inhibitor LY294002/SF1101 conjugated to the RGD-containing tetra-peptide SF1174 with potential antineoplastic and antiangiogenic activities. The targeting peptide SF1174 moiety of pan-PI3K/mTOR inhibitor SF1126 selectively binds to cell surface integrins and, upon cell entry, the agent is hydrolyzed to the active drug SF1101; SF1101 selectively inhibits all isoforms of phosphoinositide-3-kinase (PI3K) and other members of the PI3K superfamily, such as the mammalian target of rapamycin (mTOR) and DNA-PK. By inhibiting the PI3K signaling pathway, this agent may inhibit tumor cell and tumor endothelial cell proliferation and survival.
An inhibitor of cathepsin K with potential anti-osteoporotic activity. Odanacatib selectively binds to and inhibits the activity of cathepsin K, which may result in a reduction in bone resorption, improvement of bone mineral density, and a reversal in osteoporotic changes. Cathepsin K, a tissue-specific cysteine protease that catalyzes degradation of bone matrix proteins such as collagen I/II, elastin, and osteonectin plays an important role in osteoclast function and bone resorption.
A fully human IgG1 monoclonal antibody directed against the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Necitumumab binds to and blocks the ligand binding site of EGFR, thereby preventing the activation and subsequent dimerization of the receptor. This may lead to an inhibition of EGFR-dependent downstream pathways and so inhibition of EGFR-dependent tumor cell proliferation and metastasis. EGFR, a member of the epidermal growth factor family of extracellular protein ligands, may be overexpressed on the cell surfaces of various tumor cell types.
A human monoclonal antibody directed against the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) with immunosuppressive activity. Golimumab binds to TNF-a, thereby preventing TNF-a-mediated immune responses. TNF-a production is dysregulated in various auto-immune diseases and in cancer.
A selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor with antihyperglycemic activity. Dapagliflozin selectively and potently inhibits SGLT2 compared to SGLT1, which is the cotransporter of glucose in the gut.
An dispiropiperazine derivative with potential cytostatic, anti-inflammatory and immune-suppressive properties. Although the exact mechanism of action of prospidin is not known, this agent was shown to interact with DNA, disrupting cell cycle at G2 phase, inhibiting phagocytic activity of monocytes and macrophage. Prospidin has good anti-lupus activity due to its immunosuppressive effects and was also used in refractory rheumatoid arthritis as an anti-rheumatic drug. (NCI04)
A neurologic syndrome following injury of the spinal sympathetic nerves of the neck. The injury usually results from arthritis or pinching by the adjacent vertebrae. Symptoms include facial pain, chronic allergies, dizziness, neck pain, ear pain and vertigo.
A condition in which a child's body mass index (BMI) falls at or above the 95th percentile based on the normative values for the age and sex of the reference population.
An adenoma or carcinoma of the anterior lobe of the pituitary gland that produces thyrotropin.
The orally bioavailable diphosphate salt of a multiple-receptor tyrosine kinase inhibitor with potential antineoplastic activity. Motesanib selectively targets and inhibits vascular endothelial growth factor (VEGFR), platelet-derived growth factor (PDGFR), kit, and Ret receptors, thereby inhibiting angiogenesis and cellular proliferation.
A disorder characterized by an increase in sensitivity of the skin to light.
A congenital abnormality characterized by the presence of abnormally small convolutions in the brain. It results in mental retardation.
An electrocardiographic finding of pathologic Q waves with accompanying ST elevation in leads V3 and V4, which is suggestive of acute myocardial infarction of the anterior wall of the left ventricle. (CDISC)
Usually found in girls between 6 months and 6 years of age, this condition occurs wherein the labia grow together instead of as 2 separate folds, thereby blocking the opening of the vagina. It is caused by conditions such as repeated diaper rash, urine and stool infections, and sexual abuse. The condition often spontaneously corrects or responds to the application of estrogen cream.
Benign epilepsy of childhood with centrotemporal spikes (BECTS) or sharp waves, also known as rolandic epilepsy, is the most common idiopathic childhood epilepsy syndrome (Neubauer et al., 1998). It is termed 'rolandic' epilepsy because of the characteristic features of partial seizures involving the region around the lower portion of the central gyrus of Rolando. This results in classic focal seizures that affect the vocal tract, beginning with guttural sounds at the larynx and sensorimotor symptoms that progress to the tongue, mouth, and face, resulting in hypersalivation and speech arrest. Seizures most often occur in sleep shortly before awakening. The disorder occurs more often in boys than in girls (3:2). Rolandic epilepsy is considered a neurodevelopmental disorder, affecting 0.2% of the population. Affected individuals may have learning disabilities or behavioral problems; however, the seizures and accompanying problems usually remit during adolescence (summary by Strug et al., 2009). See also focal epilepsy and speech disorder (FESD; 245570), which is caused by mutation in the GRIN2A gene (138253) on chromosome 16p13. Some patients with GRIN2A mutations show features consistent with a clinical diagnosis of BECTS. Some patients with DEPDC5 (614191) mutations may show features consistent with rolandic epilepsy (see FFEVF, 604364).
A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.
An acyl-sulfonamide with potential antineoplastic activity. Selectively toxic towards tumor cells, tasisulam appears to induce tumor cell apoptosis by a mitochondrial-targeted mechanism involving the loss of mitochondrial membrane potential and induction of reactive oxygen species (ROS). In combination with an angiogenesis inhibitor, this agent may exhibit synergistic antiangiogenic activity.
A condition where one or both of the two principal meridians focus in the front of the retina when the eye is at rest. [https://www.aoa.org/]
Femur-fibula-ulna (FFU) complex is a non-lethal congenital anomaly of unknown etiology, more frequently reported in males than females, characterized by a highly variable combination of defects of the femur, fibula, and/or ulna, with striking asymmetry, including absence of the proximal part of the femur, absence of the fibula and malformation of the ulnar side of the upper limb. Axial skeleton, internal organs and intellectual function are usually normal.
A WHO grade I, slow-growing brain neoplasm of children and young adults, associated with epilepsy. Morphologically it is characterized by an angiocentric pattern, monomorphic cellular infiltrate, and ependymal differentiation.
Similar to depression in adults, childhood depression is characterized by a prolonged depressed or irritable mood accompanied by a significant loss of interest in activities, changes in appetite or sleep, decreased energy, feelings of worthlessness, and/or recurrent thoughts of death or suicide.
Congenital absence of the fetal ductus venosus.
An electrocardiographic finding of intermittent failure of atrial electrical impulse conduction to the ventricles, characterized by two or more consecutive non-conducted P waves. (CDISC)
The persistence of thromboemboli in the form of organized tissue obstructing the pulmonary arteries, leading to an increase in pulmonary vascular resistance and progressive right heart failure.
Fluctuation of temperature between hypothermia and hyperthermia
A decreased sensitivity to odorants (that is, a decreased ability to perceive odors).
Complete or severe loss of the subjective sense of taste, frequently accompanied by OLFACTION DISORDERS.
Change in or modification of actions needed to improve health state
Change in or modification of internal secretions or hormones
A feeling of mental or physical uneasiness, pain, or distress.
Change in or modification of the spirit or soul
An abnormality of the regulation of body fluids.
Voluntary cooperation of the patient in taking drugs or medicine as prescribed. This includes timing, dosage, and frequency.
Patient and designated support person communicates an understanding of medication management (i.e., medications to be used, dose, purpose, frequency, route, desired, and adverse effects).
More than adequate intake or absorption of food or nutrients
Change in or modification of the pumping action of the heart or blood vessels
Excessive tension from moving to a new location
Failure to follow therapeutic recommendations on tests to identify disease or assess health condition.
Failure to follow the prescribed diet/food intake.
Failure to follow measures to prevent injury, danger, or loss
Susceptible to behaviors in which an individual demonstrates that he or she can be physically, emotionally, and/or sexually harmful to others.
A recombinant protein with megakaryopoiesis stimulating activity. Romiplostim mimics endogenous thrombopoietin (TPO), directly binding to and activating the platelet thrombopoietin receptor (TpoR, Mpl, or CD110 antigen), a cytokine receptor belonging to the hematopoietin receptor superfamily. Activation of TpoR stimulates the proliferation and differentiation of megakaryocytes, resulting in an increase in the production of blood platelets.
The reemergence of acute undifferentiated leukemia after a period of remission.
Control of elimination of urine from the bladder
Tubulointerstitial nephritis resulting from a drug exposure.
Disease that manifests either a quantitative or a qualitative defect of factor I
Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia; 202400) or the quality (dysfibrinogenemia; 616004) of the circulating fibrinogen or both (hypodysfibrinogenemia; see 616004). Afibrinogenemia is characterized by the complete absence of immunoreactive fibrinogen. Bleeding due to afibrinogenemia usually manifests in the neonatal period, with 85% of cases presenting umbilical cord bleeding, but a later age of onst is not unusual. Bleeding may occur in the skin, gastrointestinal tract, genitourinary tract, or the central nervous system, with intracranial hemorrhage being reported as the major cause of death. Patients are susceptible to spontaneous rupture of the spleen. Menstruating women may experience menometrorrhagia. First-trimester abortion is common. Both arterial and venous thromboembolic complications have been reported (summary by de Moerloose and Neerman-Arbez, 2009). Hypofibrinogenemia is characterized by reduced amounts of immunoreactive fibrinogen. Patients are often heterozygous carriers of afibrinogenemia mutations and are usually asymptomatic. However, they may bleed when exposed to trauma or if they have a second associated hemostatic abnormality. Women may experience miscarriages. Liver disease occurs in rare cases (summary by de Moerloose and Neerman-Arbez, 2009).
Thrombotic thrombocytopenic purpura for which the cause is not present at birth.
A measurement of the total number of ectopic pregnancies experienced by a female subject.
Personal actions to follow food and fluid intake recommended by a health professional for a specific health condition
Self-initiated actions to monitor and optimize a balanced nutritional dietary regimen
Description:Specimen has been received by the participating organization/department.
Community response following a natural or man-made calamitous event
Personal actions to administer medication safely to meet therapeutic effects for a specific condition as recommended by a health professional
AF that cannot be successfully terminated by cardioversion, and longstanding (more than 1 year) AF, where cardioversion is not indicated or has not been attempted, is termed permanent. [HPO:probinson, pmid:12860883]
Personal actions to eliminate tobacco use
Severity of observed or reported prolonged generalized fatigue
An indication that a patient intends to continue pregnancy.
The formation of a blood clot in the lumen of a vessel; causes include coagulation disorders, and vascular endothelial injury.
A choline formulation of fenofibrate, a synthetic phenoxy-isobutyric acid derivate and prodrug with antihyperlipidemic activity.
A highly purified recombinant glycoprotein form of human THYROID-STIMULATING HORMONE, produced by recombinant DNA technology comprising two non-covalently linked subunits, an alpha subunit of 92 amino acid residues containing two N-linked glycosylation sites, and a beta subunit of 118 residues containing one N-linked glycosylation site. The amino acid sequence of thyrotropin alfa is identical to that of human pituitary thyroid stimulating hormone.
The smallest angle of separation that allows an image-forming device to distinguish two objects as distinct entities.
An amonafide (naphthalimide) derivative and pan-antagonist of chemokine ligand (CXCL) expression, with potential anti-angiogenic activity. Although UNBS5162 is a derivative of amonafide, this agent appears to have a different profile to that of amonafide and its exact mechanism of action remains to be fully elucidated. This agent seems to decrease the expression of various proangiogenic CXCL chemokines in vitro and may have synergistic effects with radiotherapy or chemotherapy. CXCLs are small cytokines in the CXC chemokine family that are overexpressed in certain cancers; CXCL-mediated signaling plays a key role in angiogenesis and tumor progression.
A semi-synthetic derivative of the taxane 10-deacetylbaccatin III with potential antineoplastic activities. Larotaxel binds to tubulin, promoting microtubule assembly and stabilization and preventing microtubule depolymerization, thereby inhibiting cell proliferation. As it represents poor substrate for P-glycoprotein-related drug resistance mechanisms, this agent may be useful for treating multi-drug resistant tumors. Larotaxel penetrates the blood brain barrier.
A peptide-drug conjugate containing the taxane paclitaxel covalently linked to the proprietary 19 amino acid peptide angiopep-2, in a 3:1 ratio, with potential antineoplastic activity. Upon administration, paclitaxel trevatide, via angiopep-2 moiety, binds to LRP-1 (low density lipoprotein receptor-related protein 1), which is highly expressed in blood brain barrier (BBB) and glioma cells. This binding allows the transcytosis of the agent across the BBB and the delivery of the cytotoxic agent paclitaxel. Compared to paclitaxel alone, GRN1005 is able to increase the concentration of paclitaxel in the brain and is also able to specifically deliver paclitaxel to LRP-1-overexpressing tumor cells, both in the brain and in the periphery.
A combination of two steroid sex hormones, the estrogen ethinyl estradiol and a progestin drospirenone, used for contraceptive purposes. The combination of ethinyl estradiol with drospirenone suppresses the hypothalamic-pituitary system, leading to an inhibition of the release of gonadotropin hormones follicle stimulating hormone (FSH) and luteinizing hormone (LH). The inhibition of FSH release suppresses the development of ovarian follicle. The decreased release of LH inhibits ovulation. In addition, thickening of the cervical mucus and the endometrium is promoted, thereby altering the endometrium in such a way as to discourage implantation.
A chimeric molecule directed against dopamine and somatostatin receptors with potential antineoplastic activity. Combining two pharmacological moieties, a somatostatin analogue and a dopamine agonist, dopamine-somatostatin chimeric molecule BIM-23A760 binds with high affinity to dopamine D2 receptor (D2R) and somatostatin receptor subtype 2 (SSTR2), and to a lesser extent to somatostatin receptor subtype 5 (SSTR5). This agent appears to exert its effect mainly by binding to D2R to activate the ERK1/2 and p38 MAPK pathways, thus inducing apoptosis and inhibiting cellular proliferation in non-functioning pituitary adenoma (NFPA) and neuroendocrine tumors. By binding to SSTR2, this agent may inhibit the secretion of growth hormone (GH) by the pituitary gland.
A cholesteryl ester transfer protein (CETP) inhibitor with hypocholesterolemic properties. Anacetrapib reduces the transfer of cholesteryl ester from HDL to LDL and/or VLDL thereby, producing an increase in serum HDL-cholesterol levels and a decrease in serum LDL-cholesterol levels. This agent has not yet been shown to reduce deaths associated with hypercholesterolemia.
A human single-chain variable fragment of a monoclonal antibody against fungal Hsp90 with anti-fungal activity. Efungumab binds to heat shock protein 90 (Hsp90) located on the fungal cell surface, thereby preventing cell wall synthesis and repair. This decreases the integrity of the fungal cell wall and prevents further fungal cell growth. In addition, as Hsp90 is a molecular chaperone, inhibition of its function may increase the cytotoxic effect of other antifungal agents.
An orally bioavailable inhibitor of the hepatitis C virus (HCV) protease complex comprised of non-structural protein 3 and 4A (NS3/NS4A), with activity against HCV genotype 1. Upon administration, simeprevir reversibly binds to the active center and binding site of the HCV NS3/NS4A protease and prevents NS3/NS4A protease-mediated polyprotein maturation. This disrupts both the processing of viral proteins and the formation of the viral replication complex, which inhibits viral replication in HCV genotype 1-infected host cells. NS3, a serine protease, is essential for the proteolytic cleavage of multiple sites within the HCV polyprotein and plays a key role during HCV ribonucleic acid (RNA) replication. NS4A is an activating factor for NS3. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family; HCV infection is associated with the development of hepatocellular carcinoma (HCC).
A synthetic peptide targeting the substrates of casein kinase 2 (CK2), with potential antineoplastic activity. Upon administration and nucleolar localization, CK2-targeting synthetic peptide CIGB-300 binds to phosphoacceptor sites on the CK2 substrates, in particular the oncoprotein nucleophosmin (B23 or NPM1). This blocks the activation of B23 and induces apoptosis, thereby inhibiting tumor cell growth in susceptible tumor cells. CK2, a protein kinase often overexpressed in a variety of cancer cell types, appears to be correlated with malignant transformation, tumor growth and survival. Overexpression of B23 has been correlated with increased cellular growth and proliferation as well as inhibition of differentiation and apoptosis.
A modified quinolone antibiotic with activity against human immunodeficiency virus 1. Elvitegravir is an inhibitor of viral integrase and retains activity against integrase mutants that are resistant to Raltegravir.
An orally active 2-phenylaminopyrimidine derivative with potential antineoplastic activity. INNO-406 specifically binds to and inhibits the Bcr/Abl fusion protein tyrosine kinase, an abnormal enzyme produced by Philadelphia chromosomal translocation associated with chronic myeloid leukemia (CML). Furthermore, this agent also inhibits the Src-family member Lyn tyrosine kinase, upregulated in imatinib-resistant CML cells and in a variety of solid cancer cell types. The inhibitory effect of INNO-406 on these specific tyrosine kinases decreases cellular proliferation and induces apoptosis. A high percentage of CML patients are refractory to imatinib, which sometimes results from point mutations occurring in the kinase domain of the Bcr/Abl fusion product. Due to its dual inhibitory activity, INNO-406 has been shown to overcome this particular drug resistance and to be a potent and effective agent in the treatment of imatinib-resistant CML.
A long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, with antihyperglycemic activity. Albiglutide is composed of a GLP-1 (7-36) dimer fused to recombinant human albumin. Upon subcutaneous administration, this agent has a half-life of 4-7 days and resists degradation by dipeptidyl peptidase-4 (DPP-4).
A plasmid DNA-based vaccine consisting of small biodegradable poly(lactide-co-glicolide) polymer microparticles encapsulating plasmid-DNA vector encoding a chimeric protein comprising epitopes derived from the E6 and E7 oncoproteins of the human papillomavirus (HPV) types 16 and 18, with potential antineoplastic activity. Upon intramuscular vaccination, amolimogene bepiplasmid may elicit the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells positive for HPV-16 and -18 E6 and E7 and may result in a reduction in tumor cell growth. HPV types 16 and 18 oncoproteins E6 and E7 are most commonly involved in cervical cancer.
A synthetic peptide analogue of the naturally occurring alpha-melanocyte stimulating hormone (a-MSH) with potential photoprotective activity. Mimicking the action of a-MSH, afamelanotide stimulates melanocytes to increase the production and release of melanin. Increased melanocyte melanin may protect against ultraviolet radiation (UVR)-initiated cellular DNA damage, oxidation of membrane proteins, and alterations in intracellular signaling processes in epidermal cells. Endogenously, a-MSH is released by skin cells in response to UVR exposure, stimulating melanocytes to produce and release melanin.
A synthetic small molecule inhibitor of checkpoint kinases (Chks) with potential chemosensitizing activity. AZD7762 binds to and inhibits Chks, which may prevent cell cycle arrest and subsequent nucleotide excision repair in DNA-damaged tumor cells, resulting in tumor cell apoptosis. This agent may enhance the cytotoxicity of DNA-damaging agents. Chks are protein kinases that regulate either G1/S or G2/M transitions in the cell cycle. In the presence of DNA damage or incomplete DNA replication, Chks become activated and initiate cell cycle arrest to allow DNA repair or the completion of DNA replication.
An androstene derivative that inhibits STEROID 17-ALPHA-HYDROXYLASE and is used as an ANTINEOPLASTIC AGENT in the treatment of metastatic castration-resistant PROSTATE CANCER.
An inflammation of the NASAL MUCOSA triggered by ALLERGENS.
A malignant neoplasm that arises from the hilar region of the lung.
A malignant neoplasm that affects the inner layer of the pericardium.
A unilateral absence of sensory perception of sound.
The mesylate salt of a synthetic analogue of halichondrin B, a substance derived from a marine sponge (Lissodendoryx sp.) with antineoplastic activity. Eribulin binds to the vinca domain of tubulin and inhibits the polymerization of tubulin and the assembly of microtubules, resulting in inhibition of mitotic spindle assembly, induction of cell cycle arrest at G2/M phase, and, potentially, tumor regression.
Trilateral retinoblastoma refers to bilateral (or less often unilateral) retinoblastoma associated with an intracranial primitive neuroectodermal tumor in the pineal or suprasellar region. This syndrome is often associated with a increased familial incidence of retinoblastoma. (From Cancer 86(1): 135-141, 1999).
A small-molecule bis(thio-hydrazide amide) with oxidative stress induction, pro-apoptotic, and potential antineoplastic activities. Elesclomol induces oxidative stress, creating high levels of reactive oxygen species (ROS), such as hydrogen peroxide, in both cancer cells and normal cells. Because tumor cells have elevated levels of ROS compared to normal cells, the increase in oxidative stress beyond baseline levels elevates ROS beyond sustainable levels, exhausting tumor cell antioxidant capacity, which may result in the induction of the mitochondrial apoptosis pathway. Normal cells are spared because the increase in the level of oxidative stress induced by this agent is below the threshold at which apoptosis is induced.
Charcot-Marie-Tooth disease, type 4F (CMT4F) is a demyelinating CMT peripheral sensorimotor polyneuropathy. It is a rare form of CMT4 but the few reported families are from diverse ethnic groups: Lebanese Shiite Muslims, Hispanic North Americans, Northern Europeans and a Vietnamese family. Onset generally occurs in childhood but severity varies. Early onset with delayed motor milestones, and proximal and distal muscle weakness has been reported but a family in which the clinical picture was marked initially by sensory neuropathy has also been described. CMT4 is caused by mutations in the PRX gene (19q13.2). Transmitted in an autosomal recessive manner.
ATP8B1 deficiency encompasses a phenotypic spectrum ranging from severe to intermediate to mild, based on an individual's clinical findings and laboratory test results, including liver biopsy. Severe ATP8B1 deficiency is characterized by onset of symptoms of cholestasis (pruritus and attacks of jaundice) within the first few months of life. Secondary manifestations such as coagulopathy (due to vitamin K deficiency), malabsorption, and poor weight gain may present earlier than age three months. Without surgical intervention, cirrhosis and evolution to end-stage hepatic failure and death usually ensue before the third decade. Mild ATP8B1 deficiency is characterized by intermittent episodes of cholestasis manifest as severe pruritus and jaundice; chronic liver damage does not typically develop. In contrast to patients in whom bouts of cholestasis are induced only by particular triggers known to increase risk of cholestasis (drug exposure, shifts in hormonal milieu [including those resulting from ingestion of contraceptive drugs or from pregnancy], coexistent malignancy), some or all bouts of cholestasis in individuals with mild ATP8B1 deficiency have different or unknown triggers.
The racemic isomer of lactic acid, the biologically active isoform in humans. Lactic acid or lactate is produced during fermentation from pyruvate by lactate dehydrogenase. This reaction, in addition to producing lactic acid, also produces nicotinamide adenine dinucleotide (NAD) that is then used in glycolysis to produce energy source adenosine triphosphate (ATP).
An orally available disodium salt of the Syk kinase inhibitor fostamatinib with potential anti-inflammatory and immunomodulating activities. Fostamatinib inhibits Syk kinase-mediated IgG Fc gamma receptor signaling, resulting in inhibition of the activation of mast cells, macrophages, and B-cells and related inflammatory responses and tissue damage. Syk kinase, widely expressed in hematopoietic cells, is a nonreceptor tyrosine kinase that is involved in coupling activated immunoreceptors to signal downstream events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis.
Ophthalmic solutions that include LUBRICANTS and WETTING AGENTS such as POLYETHYLENE GLYCOL; HYPROMELLOSE; GLYCEROL; PROPYLENE GLYCOL. They are used to treat conditions caused by deficient tear production such as DRY EYE SYNDROME.
Pharmacologic agents delivered into the nostrils in the form of a mist or spray.
Aspirin containing a lower dose than a standard adult tablet, usually between 81 and 100mg.
A potentially lethal complication of pheochromocytoma that may occur as a result of anaesthesia, surgery or during pregnancy and childbirth. The crisis is caused by excessive release of catecholamines and may be drug-induced secondary to histamine release, dopamine receptor blockade, or sympathomimetic action. Crisis may also result from mechanical factors such as squeeze of the tumour during surgery.
Olmsted syndrome is a rare congenital disorder characterized by bilateral mutilating palmoplantar keratoderma (PPK) and periorificial keratotic plaques with severe pruritus of lesions. Diffuse alopecia, constriction of digits, and onychodystrophy have also been reported. Infections and squamous cell carcinomas can arise on the keratotic areas (summary by Lin et al., 2012). The digital constriction ('pseudoainhum') may progress to autoamputation of fingers and toes (Olmsted, 1927).
A congenital abnormality consisting of clefting in the jaw, which results from incomplete fusion of the embryonic mandibular prominence.
A twin whose estimated fetal weight is determined to have 20% or greater difference from its sibling.
A syndrome in preterm neonates exposed to benzyl alcohol preservative in intravascular solutions that is characterized by unremitting gasping respirations and may include anion gap metabolic acidosis, neurologic deterioration, renal failure, convulsions, intraventricular hemorrhage, and cardiovascular collapse.
A disorder of cardiac function secondary to hypersensitivity reactions. It is characterized by coexistence of acute coronary syndromes and cardiac MAST CELL and PLATELET ACTIVATION. It may be induced by exposure to drugs (e.g., antibiotics, anesthetics, contrast media), food, and environmental triggers (e.g., insect bites and stings, poison ivy).
Blockage at the level of the bladder and the ureter caused by stenosis of the ureteral valves or failure of a narrow juxtavesical ureteral segment to dilate due to segmented fibrosis or localized absence of muscle.
Pelvic pain due to physiological pelvic ligament relaxation and increased joint mobility.
In general, gallbladder disease (GBD) is one of the major digestive diseases. GBD prevalence is particularly high in some minority populations in the United States, including Native and Mexican Americans. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations of GBD in western countries, including the United States. Most people with gallstones remain asymptomatic through their lifetimes; however, it is estimated that approximately 10 to 50% of individuals eventually develop symptoms. Significant risk factors associated with GBD are age, female sex, obesity (especially central obesity), lipids, diet, parity, type 2 diabetes (125853), medications, and Mexican American ethnicity. GBD appears to be strongly related to the metabolic syndrome (605552) and/or its major components, such as hyperinsulinism, dyslipidemia, and abdominal adiposity (Boland et al., 2002; Tsai et al., 2004). Infection, specifically by Helicobacter, has been implicated in cholelithiasis and cholecystitis (Silva et al., 2003; Maurer et al., 2005). Low phospholipid-associated cholelithiasis is a specific form of gallbladder disease characterized by young-adult onset of chronic cholestasis with intrahepatic sludge and cholesterol cholelithiasis. Affected individuals have recurrence of the disorder after cholecystectomy and show a favorable response to treatment with ursodeoxycholic acid (UDCA) (summary by Pasmant et al., 2012). Mutation in the ABCB4 gene can cause a spectrum of related diseases, including the more severe progressive familial intrahepatic cholestasis-3 (PFIC3; 602347), intrahepatic cholestasis of pregnancy-3 (ICP3; 614972), andoral contraceptive-induced cholestasis (OCIC; see 614972). Genetic Heterogeneity of Gallbladder Disease Two major susceptibility loci for symptomatic gallbladder disease have been identified on chromosome 1p in Mexican Americans (GBD2, 609918; GBD3, 609919). In addition, variations in the ABCG8 gene (605460) on chromosome 2p21 confer susceptibility to gallbladder disease (GBD4; 611465).
Skin eruption consisting of papules and pustules, most often appearing in the face, scalp, and upper trunk. It is usually caused by corticosteroids or epidermal growth factor receptor inhibitors.
The removal of one or more electrons from a lipid, with or without the concomitant removal of a proton or protons, by reaction with an electron-accepting substance, by addition of oxygen or by removal of hydrogen. [GOC:BHF, GOC:mah]
Hematopoiesis that occurs outside of the bone marrow. It occurs during fetal development or it may result from pathologic processes that affect the bone marrow.
Familial erythrocytosis-4 is an autosomal dominant disorder characterized by increased serum red blood cell mass and hemoglobin concentration and elevated serum erythropoietin (EPO; 133170).
The spectrum of COL4A1-related disorders includes: small-vessel brain disease of varying severity including porencephaly, variably associated with eye defects (retinal arterial tortuosity, Axenfeld-Rieger anomaly, cataract) and systemic findings (kidney involvement, muscle cramps, cerebral aneurysms, Raynaud phenomenon, cardiac arrhythmia, and hemolytic anemia). On imaging studies, small-vessel brain disease is manifest as diffuse periventricular leukoencephalopathy, lacunar infarcts, microhemorrhage, dilated perivascular spaces, and deep intracerebral hemorrhages. Clinically, small-vessel brain disease manifests as infantile hemiparesis, seizures, single or recurrent hemorrhagic stroke, ischemic stroke, and isolated migraine with aura. Porencephaly (fluid-filled cavities in the brain detected by CT or MRI) is typically manifest as infantile hemiparesis, seizures, and intellectual disability; however, on occasion it can be an incidental finding. HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome usually associates asymptomatic small-vessel brain disease, cerebral large vessel involvement (i.e., aneurysms), and systemic findings involving the kidney, muscle, and small vessels of the eye. Two additional phenotypes include isolated retinal artery tortuosity and nonsyndromic autosomal dominant congenital cataract.
Lipoprotein glomerulopathy is an uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries (Saito et al., 2006). It mainly affects people of Japanese and Chinese origin; in these populations, it is associated with mutations in the gene that encodes apolipoprotein E (APOE; 107741). The disorder had rarely been described in Caucasians.
Familial cold autoinflammatory syndrome-2 (FCAS2) is an autosomal dominant autoinflammatory disorder characterized by episodic and recurrent rash, urticaria, arthralgia, myalgia, and headache. In most patients, these episodes are accompanied by fever and serologic evidence of inflammation. Most, but not all, patients report exposure to cold as a trigger for the episodes. Additional features may include abdominal pain, thoracic pain, and sensorineural deafness. The age at onset is variable, ranging from the first year of life to middle age, and the severity and clinical manifestations are heterogeneous (summary by Shen et al., 2017). For a phenotypic description and a discussion of genetic heterogeneity of familial cold autoinflammatory syndrome, see FCAS1 (120100).
Mutations in the KCTD7 gene cause a severe neurodegenerative phenotype characterized by onset of intractable myoclonic seizures before age 2 years and accompanied by developmental regression. The initial description was consistent with a form of progressive myoclonic epilepsy (designated here as EPM3), whereas a later report identified intracellular accumulation of autofluorescent lipopigment storage material, consistent with neuronal ceroid lipofuscinosis (designated CLN14). Ultrastructural findings on skin biopsies thus appear to be variable. However, clinical features are generally consistent between reports (summary by Staropoli et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800). For a general phenotypic description and a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis, see CLN1 (256730).
Excretion of oligosaccharides conjugated to sialic acid in the urine.
Mucolipidosis II (ML II, I-cell disease) is a slowly progressive inborn error of metabolism with clinical onset at birth and fatal outcome most often in early childhood. Postnatal growth is limited and often ceases in the second year of life; contractures develop in all large joints. The skin is thickened, facial features are coarse, and gingiva are hypertrophic. Orthopedic abnormalities present at birth may include thoracic deformity, kyphosis, clubfeet, deformed long bones, and/or dislocation of the hip(s). Already in infancy skeletal radiographs reveal dysostosis multiplex. All children appear to have cardiac involvement, most commonly thickening and insufficiency of the mitral valve and, less frequently, the aortic valve. Progressive mucosal thickening narrows the airways and gradual stiffening of the thoracic cage contributes to respiratory insufficiency, the most common cause of death.
Overgrowth of the proximal part of the fibula.
High urine calcium in the presence of hypocalcemia.
An increased concentration of magnesium the urine.
A lower than normal concentration of citrate(3-) in the urine.
Increased susceptibility to Staphylococcus aureus infections, as manifested by recurrent episodes of Staphylococcus aureus infection.
Autosomal recessive dopa responsive dystonia (DYT5b) is a very rare neurometabolic disorder with a spectrum of symptoms ranging from those seen in dopa responsive dystonia to progressive infantile encephalopathy. Disease presents in infancy (most frequently in the first year of life) with a progressive hypokinetic rigid syndrome, involuntary jerky movements, postural tremor, or gait disturbances that may fluctuate during the day and show good or excellent responsiveness to levodopa in most cases. DYT5b is caused by mutations in the tyrosine hydroxylase TH gene (11p15.5). Inherited in an autosomal recessive manner.
An increased concentration of glycerol in the urine.
Junctional epidermolysis bullosa inversa is a rare severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by blistering and erosions confined to intertriginous skin sites, the esophagus, and vagina.
An extremely rare type of spondyloepiphyseal dysplasia described in about 5 patients to date with clinical signs including short stature, peculiar facies with blepharophimosis, upward slanted eyes, abundant eyebrows and eyelashes, coarse voice, and short hands and feet.
An excessive concavity of the anterior surface of one or more vertebral bodies.
Salih myopathy is characterized by muscle weakness (manifest during the neonatal period or in early infancy) and delayed motor development; children acquire independent walking between ages 20 months and four years. In the first decade of life, global motor performance is stable or tends to improve. Moderate joint and neck contractures and spinal rigidity may manifest in the first decade but become more obvious in the second decade. Scoliosis develops after age 11 years. Cardiac dysfunction manifests between ages five and 16 years, progresses rapidly, and leads to death between ages eight and 20 years, usually from heart rhythm disturbances.
Tendon reflexes that are noticably more active than usual (conventionally denoted 3+ on clinical examnation). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Nonsyndromic hearing loss and deafness (DFNB1) is characterized by congenital non-progressive mild-to-profound sensorineural hearing impairment. No other associated medical findings are present.
Inflammation characterised by gingival redness and swelling with spontaneous bleeding.
Chronic hepatitis characterized by parenchymal inflammation with formation of large multinucleated hepatocytes in response to a variety of insults to the liver.
A rare genetic developmental defect during embryogenesis syndrome with the triad of pancreatic fibrosis (and cysts, with a reduction of parenchymal tissue), renal dysplasia (with peripheral cortical cysts, primitive collecting ducts, glomerular cysts and metaplastic cartilage) and hepatic dysgenesis (enlarged portal areas containing numerous elongated binary profiles with a tendency to perilobular fibrosis). Situs abnormalities, skeletal anomalies and anencephaly have also been associated. Patients that survive the neonatal period present renal insufficiency, chronic jaundice and insulin-dependant diabetes.
This autosomal recessive disorder is designated Meckel syndrome type 7 based on the classic phenotypic triad of (1) cystic renal disease; (2) a central nervous system abnormality, and (3) hepatic abnormalities, as defined by Meckel (1822), Salonen (1984), and Logan et al. (2011). According to these criteria, polydactyly is a variable feature. Herriot et al. (1991) and Al-Gazali et al. (1996) concluded that Dandy-Walker malformation can be the phenotypic manifestation of a central nervous system malformation in MKS. For a general phenotypic description and a discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
A reduction in the count of nephrons per kidney. [Eurenomics:ewuehl]
A congenital disorder of the intrahepatic bile ducts characterized by abnormal embryonal development of the ductal plates.
) described in a single patient with adult onset microcytic hypochromic anemia with liver iron overload and type 2 diabetes.
Autosomal recessive amelogenesis imperfecta pigmented hypomaturation type is characterized by enamel of normal thickness that is hypomineralized and has a mottled appearance. The slightly soft enamel detaches easily from the dentin, and radiographs show a lack of contrast between enamel and dentin (Witkop, 1989). Genetic Heterogeneity of the Hypomaturation Type of Amelogenesis Imperfecta See also AI2A2 (612529), caused by mutation in the MMP20 gene (604629); AI2A3 (613211), caused by mutation in the WDR72 gene (613214); and AI2A4 (614832), caused by mutation in the C4ORF26 gene (614829).
An increased concentration of threonine in the urine.
Underdevelopment of the fovea centralis.
SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities.All people with this condition have extremely short stature with particularly short arms and legs. Other features include unusual bowing of the leg bones; a small chest with short ribs and curved collar bones; short, broad fingers; and folds of extra skin on the arms and legs. Structural abnormalities of the brain cause seizures, profound developmental delay, and intellectual disability. Several affected individuals also have had episodes in which their breathing slows or stops for short periods (apnea). Acanthosis nigricans, a progressive skin disorder characterized by thick, dark, velvety skin, is another characteristic feature of SADDAN that develops in infancy or early childhood.
Inability to elicit tendon reflexes in the upper limbs.
Hereditary spherocytosis is a condition that affects red blood cells. People with this condition typically experience a shortage of red blood cells (anemia), yellowing of the eyes and skin (jaundice), and an enlarged spleen (splenomegaly). Most newborns with hereditary spherocytosis have severe anemia, although it improves after the first year of life. Splenomegaly can occur anytime from early childhood to adulthood. About half of affected individuals develop hard deposits in the gallbladder called gallstones, which typically occur from late childhood to mid-adulthood.There are four forms of hereditary spherocytosis, which are distinguished by the severity of signs and symptoms. They are known as the mild form, the moderate form, the moderate/severe form, and the severe form. It is estimated that 20 to 30 percent of people with hereditary spherocytosis have the mild form, 60 to 70 percent have the moderate form, 10 percent have the moderate/severe form, and 3 to 5 percent have the severe form.People with the mild form may have very mild anemia or sometimes have no symptoms. People with the moderate form typically have anemia, jaundice, and splenomegaly. Many also develop gallstones. The signs and symptoms of moderate hereditary spherocytosis usually appear in childhood. Individuals with the moderate/severe form have all the features of the moderate form but also have severe anemia. Those with the severe form have life-threatening anemia that requires frequent blood transfusions to replenish their red blood cell supply. They also have severe splenomegaly, jaundice, and a high risk for developing gallstones. Some individuals with the severe form have short stature, delayed sexual development, and skeletal abnormalities.
The plasma level of vitamin B12 is a modifiable quantitative trait associated with many diseases (Hazra et al., 2008). Vitamin B12 found in meat and milk products is composed of corrin and cobalt rings and is necessary for the formation of red blood cells, DNA synthesis during cell division, and maintenance of the myelin nerve sheath, among other functions. Deficiency in vitamin B12, clinically associated with pernicious anemia, cardiovascular disease, cancer, and neurodegenerative disorders, is often related to poor intestinal B12 absorption rather than direct dietary deficiency.
Heterozygous protein C deficiency is characterized by recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic (Millar et al., 2000). Individuals with decreased amounts of protein C are classically referred to as having type I deficiency and those with normal amounts of a functionally defective protein as having type II deficiency (Bertina et al., 1984). Acquired protein C deficiency is a clinically similar disorder caused by development of an antibody against protein C. Clouse and Comp (1986) reviewed the structural and functional properties of protein C and discussed both hereditary and acquired deficiency of protein C.
Increased dimension of the sclera in the anterior-posterior axis.
Splitting of the retinal layers in the macula.
A reduction of bone mineral density, that is, of the amount of matter per cubic centimeter of bones.
A dislocation of the head of the radius from its socket in the elbow joint in an anterior direction.
A response indicating that a person's walking ability is limited, significantly less postoperatively.
Tremor of the trunk in an anterior-posterior plane at 3-4 Hz.
Loeys-Dietz syndrome (LDS) is characterized by vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections), skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus, cervical spine malformation and/or instability), craniofacial features (widely spaced eyes, strabismus, bifid uvula / cleft palate, and craniosynostosis that can involve any sutures), and cutaneous findings (velvety and translucent skin, easy bruising, and dystrophic scars). Individuals with LDS are predisposed to widespread and aggressive arterial aneurysms and pregnancy-related complications including uterine rupture and death. Individuals with LDS can show a strong predisposition for allergic/inflammatory disease including asthma, eczema, and reactions to food or environmental allergens. There is also an increased incidence of gastrointestinal inflammation including eosinophilic esophagitis and gastritis or inflammatory bowel disease. Wide variation in the distribution and severity of clinical features can be seen in individuals with LDS, even among affected individuals within a family who have the same pathogenic variant.
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
A mild form of familial adenomatous polyposis with main features described as the presence of fewer than 100 adenomatous polyposis, a more proximal colonic location, a delayed age of colorectal cancer onset and a more limited expression of the extracolonic features.
A tendency of teeth to fracture as manifested by a history of repeated fracture of the dental enamel without adequate trauma.
Multicentric carpotarsal osteolysis syndrome is a rare skeletal disorder, usually presenting in early childhood with a clinical picture mimicking juvenile rheumatoid arthritis. Progressive destruction of the carpal and tarsal bone usually occurs and other bones may also be involved. Chronic renal failure is a frequent component of the syndrome. Mental retardation and minor facial anomalies have been noted in some patients. Autosomal dominant inheritance has been documented in many families (Pai and Macpherson, 1988). See also Torg-Winchester syndrome (259600), an autosomal recessive multicentric osteolysis syndrome.
RAS-associated leukoproliferative disorder is characterized by lymphadenopathy, splenomegaly, and variable autoimmune phenomena, including autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, and neutropenia. Laboratory studies show an expansion of lymphocytes due to defective apoptosis, as well as significant autoantibodies. Some patients have recurrent infections, and there may be an increased risk of hematologic malignancy (summary by Oliveira, 2013 and Niemela et al., 2010). The disorder shows significant overlap with autoimmune lymphoproliferative syndrome (ALPS; 601859) and was originally designated ALPS IV.
The formation of new bone along the cortex and underneath the periosteum of a bone.
Clopidogrel is a thienopyridine antiplatelet agent that prevents platelet activation and aggregation by irreversibly inhibiting the P2Y12 ADP receptors. As a pro-drug, clopidogrel requires hepatic biotransformation to form an active metabolite. This conversion is composed of two sequential oxidative steps, which involve cytochrome P450-2C19 (CYP2C19) and other enzymes. Genetic variants in CYP2C19 such as CYP2C19*2, along with other genetic and non-genetic factors, are known to influence variability in clopidogrel response. Specific CYP2C19 variants impair formation of the active clopidogrel metabolite, which results in reduced platelet inhibition. Among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI), patients with specific variants in the CYP2C19 gene might be at increased risk for serious adverse cardiovascular events and may benefit from an alternative antiplatelet therapy as compared to patients without these variants. Guidelines regarding the use of pharmacogenomic tests in dosing for clopidogrel have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
3q29 recurrent deletion is characterized by global developmental delay and/or intellectual disability, and commonly, speech delay, and increased risk for neuropsychiatric disorders (including autism spectrum disorder, anxiety disorder, psychosis, and/or schizophrenia). Other common findings are failure to thrive and feeding problems in infancy that persist into childhood, heart defects (especially patent ductus arteriosus), gastrointestinal disorders (including gastroesophageal reflux disease), and dental abnormalities. To date findings in fewer than 50 affected individuals have been reported.
Müllerian aplasia and hyperandrogenism is a condition that affects the reproductive system in females. This condition is caused by abnormal development of the Müllerian ducts, which are structures in the embryo that develop into the uterus, fallopian tubes, cervix, and the upper part of the vagina. Individuals with Müllerian aplasia and hyperandrogenism typically have an underdeveloped or absent uterus and may also have abnormalities of other reproductive organs. Women with this condition have normal female external genitalia, and they develop breasts and pubic hair normally at puberty; however, they do not begin menstruation by age 16 (primary amenorrhea) and will likely never have a menstrual period. Affected women are unable to have children (infertile).Women with Müllerian aplasia and hyperandrogenism have higher-than-normal levels of male sex hormones called androgens in their blood (hyperandrogenism), which can cause acne and excessive facial hair (facial hirsutism). Kidney abnormalities may be present in some affected individuals.
Reduction in the vertical distance between the upper and lower eyelids.
Increase in size of a peripheral nerve. This finding can be appreciated by palpation along the axis of the nerve.
Dyschromatosis universalis hereditaria (DUH) is a rare autosomal dominant genodermatosis characterized by irregularly shaped, asymptomatic hyper- and hypopigmented macules that appear in infancy or early childhood and occur in a generalized distribution over the trunk, limbs, and sometimes the face. Involvement of the palms or soles is unusual. Abnormalities of hair and nails have been reported, and DUH may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications (summary by Zhang et al., 2013). For a discussion of genetic heterogeneity of dyschromatosis universalis hereditaria, see DUH1 (127500).
Kahrizi syndrome is an autosomal recessive neurodevelopmental disorder characterized by mental retardation, cataracts, coloboma, kyphosis, and coarse facial features (summary by Kahrizi et al., 2009). See also congenital disorder of glycosylation type Iq (CDG1Q; 612379), an allelic disorder with overlapping features.
EPB42-related hereditary spherocytosis (EPB42-HS) is a chronic non-immune hemolytic anemia that is usually of mild to moderate severity. EPB42-HS can present with jaundice as early as the first 24 hours of life or can present later in childhood with anemia resulting from a hemolytic crisis or aplastic crisis (usually associated with a viral infection). In addition to the hematologic manifestations, serious complications include splenomegaly that can become evident in early childhood and cholelithiasis that usually becomes evident in the second or third decade of life. Typical laboratory findings in EPB42-HS include anemia (decreased hemoglobin [Hgb] level) and reticulocytosis (increased percent of reticulocytes), with high mean corpuscular hemoglobin concentration (MCHC), presence of spherocytes in the peripheral blood smear, significantly decreased or absent haptoglobin, mildly increased osmotic fragility, and decreased maximal deformability index (DImax) with increased Omin (osmolality at which 50% of red blood cells hemolyze) measured by ektacytometry.
Nonsyndromic hearing loss and deafness, DFNA3 is characterized by pre- or postlingual, mild-to-profound progressive high-frequency sensorineural hearing impairment. Affected individuals have no other associated medical findings.
15q duplication syndrome and related disorders (dup15q) are caused by presence of at least one extra maternally derived copy of the Prader-Willi/Angelman critical region (PWACR) within chromosome 15q11.2-q13.1. The extra copy or copies most commonly arise by one of two mechanisms: A maternal isodicentric 15q11.2-q13.1 supernumerary chromosome – idic(15) – typically comprising two extra copies of 15q11.2-q13.1 and resulting in tetrasomy for 15q11.2-q13.1 (~80% of cases); A maternal interstitial 15q11.2-q13.1 duplication that typically includes one extra copy of 15q11.2-q13.1 within chromosome 15, resulting in trisomy for 15q11.2-q13.1 (~20% of cases). Dup15q is characterized by hypotonia and motor delays, intellectual disability, autism spectrum disorder (ASD), and epilepsy including infantile spasms. Rarely, dup15q may also be associated with psychosis or sudden unexplained death. Those with maternal idic(15) are typically more severely affected than those with an interstitial duplication.
22q11.2 duplication is defined for this GeneReview as the presence of a common 3-Mb or 1.5-Mb proximal tandem duplication. The 22q11.2 duplication phenotype appears to be generally mild and highly variable; findings range from apparently normal to intellectual disability/learning disability, delayed psychomotor development, growth retardation, and/or hypotonia. The high frequency with which the 22q11.2 duplication is found in an apparently normal parent of a proband suggests that many individuals can harbor a duplication of 22q11.2 with no discernible phenotypic effect.
Fibrosis of the external ocular muscles such that the eyes of affected individuals are partially or completely fixed in a strabismic position. Residual eye movements are significantly limited.
A rare haemolytic anaemia due to an erythrocyte nucleotide metabolism disorder characterised by moderate to severe chronic nonspherocytic haemolytic anaemia that may require regular blood transfusions and/or splenectomy and may be associated with psychomotor impairment.
SYNGAP1-related intellectual disability (SYNGAP1-ID) is characterized by developmental delay (DD) or intellectual disability (ID) (100% of affected individuals), generalized epilepsy (~84%), and autism spectrum disorder (ASD) and other behavioral abnormalities (=50%). To date more than 50 individuals with SYNGAP1-ID have been reported. In the majority DD/ID was moderate to severe; in some it was mild. The epilepsy is generalized; a subset of individuals with epilepsy have myoclonic astatic epilepsy (Doose syndrome) or epilepsy with myoclonic absences. Behavioral abnormalities can include stereotypic behaviors (e.g., hand flapping, obsessions with certain objects) as well as poor social development. Feeding difficulties can be significant in some.
Rupture of an intracranial aneurysm, an outpouching or sac-like widening of a cerebral artery, leads to a subarachnoid hemorrhage, a sudden-onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension, and excessive alcohol intake are associated with subarachnoid hemorrhage (summary by Krischek and Inoue, 2006). For a discussion of genetic heterogeneity of intracranial berry aneurysms, see ANIB1 (105800).
G6PC3 deficiency is characterized by severe congenital neutropenia which occurs in a phenotypic continuum that includes the following: Isolated severe congenital neutropenia (nonsyndromic). Classic G6PC3 deficiency (severe congenital neutropenia plus cardiovascular and/or urogenital abnormalities). Severe G6PC3 deficiency (classic G6PC3 deficiency plus involvement of non-myeloid hematopoietic cell lines, additional extra-hematologic features, and pulmonary hypertension; known as Dursun syndrome). Neutropenia usually presents with recurrent bacterial infections in the first few months of life. Intrauterine growth restriction (IUGR), failure to thrive (FTT), and poor postnatal growth are common. Other findings in classic and severe G6PC3 deficiency can include inflammatory bowel disease (IBD) resembling Crohn's disease, and endocrine disorders (growth hormone deficiency, hypogonadotropic hypogonadism, and delayed puberty).
Reduced diameter of a long bone with a more pronounced reduction of the diameter of the diaphysis of the long bones.
Infection-induced acute encephalopathy 3 (IIAE3) is the susceptibility to recurrent acute necrotizing encephalopathy (ANE) caused by a heterozygous pathogenic variant in RANBP2. ANE refers to the specific neurologic presentation in which bilateral symmetric thalamic, midbrain, and/or hindbrain lesions occur within days following the onset of an acute viral illness caused by influenza A, influenza B, parainfluenza II, human herpes virus 6, coxsackie virus, or an enterovirus. Although most IIAE3 occurs before age six years, first episodes have been observed in teenagers and adults. ANE begins within 12 hours to three or four days of the first awareness of viral symptoms (fever, cough, rhinorrhea, vomiting, diarrhea, and malaise). The most common sign of ANE is lethargy that progresses to coma (which may last for weeks) and seizures (in 50%). One third of affected individuals die during the acute phase of the encephalopathy; of the survivors, one half have permanent neurologic damage and the remainder have no discernible residual symptoms. Fifty per cent of persons with IIAE3 will have at least one repeat episode and some will have multiple repeat episodes
Presence of persistent islands of renal blastema in the postnatal kidney. Nephroblastomatosis represents a complex abnormality of nephrogenesis and has been defined as the persistence of metanephricblastema into infancy and childhood.
Absence of globe, optic nerve, chiasm and optic tracts. No evidence of ocular tissue on MRI scan or examination.
Clay colored stools lacking bile pigment.
Dyschromatosis universalis hereditaria (DUH) is a rare autosomal dominant genodermatosis characterized by irregularly shaped, asymptomatic hyper- and hypopigmented macules that appear in infancy or early childhood and occur in a generalized distribution over the trunk, limbs, and sometimes the face. Involvement of the palms or soles is unusual. Abnormalities of hair and nails have been reported, and DUH may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications (summary by Zhang et al., 2013). The autosomal dominant SASH1-associated DUH1 phenotype is characterized by generalized lentigines accompanied by mottled hyper- and hypopigmentation (Zhang et al., 2017). DUH is distinct from dyschromatosis symmetrica hereditaria (DSH; 127400), which also occurs particularly in Japanese and Korean individuals, but shows a characteristic mixture of hyper- and hypopigmented macules limited largely to the dorsal aspects of the hands and feet (Suenaga, 1952). Gao et al. (2005) noted that lesions associated with DUH appear within the first year of life predominantly on the trunk, whereas the age of onset of DSH is approximately 6 years and lesions appear predominantly on the extremities. Genetic Heterogeneity of Dyschromatosis Universalis Hereditaria Dyschromatosis universalis hereditaria-2 (DUH2; 612715) maps to chromosome 12q21-q23. DUH3 (615402) is caused by mutation in the ABCB6 gene (605452) on chromosome 2q35.
The DDOD syndrome is characterized by autosomal dominant inheritance of congenital deafness and onychodystrophy. Conical, hypoplastic teeth is also a feature (Robinson et al., 1962). See also DOOR syndrome (220500), an autosomal recessive disorder, which includes congenital deafness, onychodystrophy, osteodystrophy, and mental retardation.
Craniodiaphyseal dysplasia is a severe bone dysplasia characterized by massive generalized hyperostosis and sclerosis, especially involving the skull and facial bones. Progressive bony encroachment upon cranial foramina leads to severe neurologic impairment in childhood (summary by Brueton and Winter, 1990). The sclerosis is so severe that the resulting facial distortion is referred to as 'leontiasis ossea' (leonine facies), and the bone deposition results in progressive stenosis of craniofacial foramina (summary by Kim et al., 2011).
Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family.Nonsyndromic holoprosencephaly can be grouped into four types according to the degree of brain division. From most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In the most severe forms of nonsyndromic holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe nonsyndromic holoprosencephaly die before birth or soon after. In the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). The life expectancy of these affected individuals varies depending on the severity of symptoms.People with nonsyndromic holoprosencephaly often have a small head (microcephaly), although they can develop a buildup of fluid in the brain (hydrocephalus) that causes increased head size (macrocephaly). Other features may include an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip), one central front tooth instead of two (a single maxillary central incisor), and a flat nasal bridge. The eyeballs may be abnormally small (microphthalmia) or absent (anophthalmia).Some individuals with nonsyndromic holoprosencephaly have a distinctive pattern of facial features, including a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). In general, the severity of facial features is directly related to the severity of the brain abnormalities. However, individuals with mildly affected facial features can have severe brain abnormalities. Some people do not have apparent structural brain abnormalities but have some of the facial features associated with this condition. These individuals are considered to have a form of the disorder known as microform holoprosencephaly and are typically identified after the birth of a severely affected family member.Most people with nonsyndromic holoprosencephaly have developmental delay and intellectual disability. Affected individuals also frequently have a malfunctioning pituitary gland, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. Most commonly, people with nonsyndromic holoprosencephaly and pituitary dysfunction develop diabetes insipidus, a condition that disrupts the balance between fluid intake and urine excretion. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature, heart rate, and breathing. The sense of smell may be diminished (hyposmia) or completely absent (anosmia) if the part of the brain that processes smells is underdeveloped or missing.
Autosomal recessive amelogenesis imperfecta pigmented hypomaturation type is characterized by enamel of normal thickness that is hypomineralized and has a mottled appearance. The slightly soft enamel detaches easily from the dentin, and radiographs show a lack of contrast between enamel and dentin (Witkop, 1989).
Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis, and early onset of diabetes (Garg, 2004). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594).
Vernes et al. (2008) identified polymorphisms and a haplotype within the CNTNAP2 gene (604569) on chromosome 7q35-q36 implicated in the endophenotype of nonsense word repetition as a marker of specific language impairment.
Chromosome 2p16.1-p15 deletion syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and variable but distinctive dysmorphic features, including microcephaly, bitemporal narrowing, smooth and long philtrum, hypertelorism, downslanting palpebral fissures, broad nasal root, thin upper lip, and high palate. Many patients have behavioral disorders, including autistic features, as well as structural brain abnormalities, such as pachygyria or hypoplastic corpus callosum. Those with deletions including the BCL11A gene (606557) also have persistence of fetal hemoglobin (HbF), which is asymptomatic and does not affected hematologic parameters or susceptibility to infection (summary by Funnell et al., 2015). Point mutation in the BCL11A gene causes intellectual developmental disorder with persistence of fetal hemoglobin (617101), which shows overlapping features. See also fetal hemoglobin quantitative trait locus-5 (HBFQTL5; 142335).
1q21.1 microduplication is a chromosomal change in which a small amount of genetic material on chromosome 1 is abnormally copied (duplicated). The duplication occurs on the long (q) arm of the chromosome at a location designated q21.1.Some people with a 1q21.1 microduplication have developmental delay and intellectual disability that is typically mild to moderate. Individuals with this condition can also have features of autism spectrum disorder. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. Expressive language skills (vocabulary and the production of speech) tend to be more impaired than receptive language skills (the ability to understand speech) in affected individuals. In childhood, 1q21.1 microduplications may also be associated with an increased risk of attention deficit hyperactivity disorder and other behavioral problems. Psychiatric disorders such as schizophrenia or mood disorders such as anxiety or depression occur in some affected individuals, usually during adulthood. Rarely, recurrent seizures (epilepsy) occur in people with a 1q21.1 microduplication.Some individuals with a 1q21.1 microduplication are born with malformations of the heart, including a particular combination of heart defects known as tetralogy of Fallot. Less commonly, other physical malformations such as the urethra opening on the underside of the penis (hypospadias) in males, inward- and upward-turning feet (clubfeet), or misalignment of the hip joint (hip dysplasia) are present at birth. Individuals with a 1q21.1 microduplication may also have a larger than average head size or taller than average adult stature. Some have slightly unusual facial features such as wide-set eyes or low-set ears. As adults, individuals with a 1q21.1 microduplication may be prone to develop cysts, swollen and knotted (varicose) veins, or carpal tunnel syndrome, which is characterized by numbness, tingling, and weakness in the hands and fingers. However, there is no particular pattern of physical abnormalities that characterizes 1q21.1 microduplications. Signs and symptoms related to the chromosomal change vary even among affected members of the same family. Some people with the duplication have no identified physical, intellectual, or behavioral abnormalities.
The 1q21.1 recurrent microdeletion itself does not appear to lead to a clinically recognizable syndrome as some persons with the deletion have no obvious clinical findings and others have variable findings that most commonly include microcephaly (50%), mild intellectual disability (30%), mildly dysmorphic facial features, and eye abnormalities (26%). Other findings can include cardiac defects, genitourinary anomalies, skeletal malformations, and seizures (~15%). Psychiatric and behavioral abnormalities can include autism spectrum disorders, attention deficit hyperactivity disorder, autistic features, and sleep disturbances.
For a detailed discussion of the WAGR syndrome, see 194072. In a subgroup of individuals with the WAGR syndrome, obesity develops. The phenotype in this subset is associated with haploinsufficiency for the BDNF gene.
A test result indicating the presence of red cells of various sizes and shapes in the peripheral blood.
A subtype of ductal pancreatic carcinoma that is thought to originate from squamous metaplasia of pancreatic ductal epithelium.
The presence of developmental dysplasia of the optic nerve.
A rare multiple congenital anomalies syndrome with characteristics of mild intellectual disability, short stature, cardiac anomalies, mild dysmorphic features (macrocephaly, prominent forehead, hypertelorism, exophthalmos), cutis laxa, joint hyperlaxity, wrinkled palms and soles and skeletal anomalies (sella turcica, wide ribs and small vertebral bodies).
Oculocutaneous albinism (OCA) is a heterogeneous autosomal recessive disorder, with a worldwide prevalence of approximately 1:17,000. It manifests as a reduction or complete loss of melanin in the skin, hair, and eyes, often accompanied by eye symptoms such as photophobia, strabismus, moderate to severe visual impairment, and nystagmus (summary by Wei et al., 2013). For a discussion of genetic heterogeneity of oculocutaneous albinism, see OCA1 (203100). For a general phenotypic description and a discussion of genetic heterogeneity of variation in skin, hair, and eye pigmentation, see SHEP1 (227220).
An elevated level of insulin-like growth factor 1 (IGF1) in the blood circulation.
Age-related hearing impairment (ARHI), or presbycusis, is the progressive bilaterally symmetric deterioration of hearing ability that occurs with aging. Studies of the cochlea in many animal species and of the histopathology of human temporal bones have shown that stria vascularis volumes and spiral ganglion cell, inner hair cell, and outer hair cell populations, as well as many other cochlear cell types and structures, undergo age-related degeneration. Environmental risk factors for ARHI include noise exposure, smoking, ototoxic medication, and cardiovascular disease. Heritability estimates vary between 0.25 and 0.75 depending on, among other factors, study design (family vs twins), age range of the study population, and the phenotype studied (Huyghe et al., 2008).
POLR3-related leukodystrophy, a hypomyelinating leukodystrophy with specific features on brain MRI, is characterized by varying combinations of four major clinical findings: Neurologic dysfunction, typically predominated by motor dysfunction (progressive cerebellar dysfunction, and to a lesser extent extrapyramidal [i.e., dystonia], pyramidal [i.e., spasticity] and cognitive dysfunctions). Abnormal dentition (delayed dentition, hypodontia, oligodontia, and abnormally placed or shaped teeth). Endocrine abnormalities such as short stature (in ~50% of individuals) with or without growth hormone deficiency, and more commonly, hypogonadotropic hypogonadism manifesting as delayed, arrested, or absent puberty. Ocular abnormality in the form of myopia, typically progressing over several years and becoming severe. POLR3-related leukodystrophy and 4H leukodystrophy are the two recognized terms for five previously described overlapping clinical phenotypes (initially described as distinct entities before their molecular basis was known). These include: Hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); Ataxia, delayed dentition, and hypomyelination (ADDH); Tremor-ataxia with central hypomyelination (TACH); Leukodystrophy with oligodontia (LO); Hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). Age of onset is typically in early childhood but later-onset cases have also been reported. An infant with Wiedemann-Rautenstrauch syndrome (neonatal progeroid syndrome) was recently reported to have pathogenic variants in POLR3A on exome sequencing. Confirmation of this as a very severe form of POLR3-related leukodystrophy awaits replication in other individuals with a clinical diagnosis of Wiedemann-Rautenstrauch syndrome.
TUBB4A-related leukodystrophy comprises a phenotypic spectrum in which the MRI findings range from hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) at the severe end to isolated hypomyelination at the mild end. Progressive neurologic findings reflect involvement of the pyramidal tracts (spasticity, brisk deep tendon reflexes, and Babinski sign), extrapyramidal system (rigidity, dystonia, choreoathetosis, oculogyric crisis, and perioral dyskinesia), cerebellum (ataxia, intention tremor, dysmetria), and bulbar function (dysarthria, dysphonia, and swallowing). Cognition is variably affected, usually less severely than motor function. Typically, those with H-ABC present in early childhood (ages one to three years) and those with isolated hypomyelination in later childhood or adulthood. The rate of progression varies with disease severity.
PRICKLE1-related progressive myoclonus epilepsy (PME) with ataxia is characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, varying degrees of neurologic decline especially manifest as ataxia, and normal intellectual abilities. Onset of symptoms is between ages five and ten years. Action myoclonus may affect the limbs or bulbar muscles, sometimes with spontaneous myoclonus of facial muscles. Marked dysarthria may occur. Seizures can be myoclonic or tonic-clonic and are often nocturnal.
Androgenetic alopecia is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic ""M"" shape. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness.The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede. Androgenetic alopecia in women rarely leads to total baldness.Androgenetic alopecia in men has been associated with several other medical conditions including coronary heart disease and enlargement of the prostate. Additionally, prostate cancer, disorders of insulin resistance (such as diabetes and obesity), and high blood pressure (hypertension) have been related to androgenetic alopecia. In women, this form of hair loss is associated with an increased risk of polycystic ovary syndrome (PCOS). PCOS is characterized by a hormonal imbalance that can lead to irregular menstruation, acne, excess hair elsewhere on the body (hirsutism), and weight gain.
An abnormal osseous union (fusion) between the proximal portions of the radius and the ulna.
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), reports of several families with expression of more than one variant of porokeratosis among members, and of individuals expressing more than one variant, suggest that the distinctions among these variants may be artificial. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life (summary by Wu et al., 2004 and Zhang et al., 2012).
Ehlers-Danlos syndrome spondylodysplastic type 3 is characterized by short stature, hyperelastic skin and hypermobile joints, protuberant eyes with bluish sclerae, finely wrinkled palms, and characteristic radiologic features (Giunta et al., 2008). For a discussion of genetic heterogeneity of the spondylodysplastic type of Ehlers-Danlos syndrome, see 130070.
Pulli et al. (2008) hypothesized that musical aptitude is an innate cognitive ability that can be partly explained by genetic regulation. Exceptional phenotypes of musical aptitude such as absolute pitch (159300) and amusia (191200) are also thought to have a genetic component. Since musical ability varies between individuals, it is likely a complex trait influenced by several underlying genes, environmental factors, and their interactions.
SATB2-associated syndrome (SAS) is a multisystem disorder characterized by significant neurodevelopmental compromise with limited to absent speech, behavioral issues, and craniofacial anomalies. All individuals described to date have manifest developmental delay / intellectual disability, with severe speech delay. Affected individuals often have hypotonia and feeding difficulties in infancy. Behavioral issues may include autistic features, hyperactivity, and aggressiveness. Craniofacial anomalies may include palatal abnormalities (cleft palate, high-arched palate, and bifid uvula), micrognathia, and abnormal shape or size of the upper central incisors. Less common features include skeletal anomalies (osteopenia, pectus deformities, kyphosis/lordosis, and scoliosis), growth restriction, strabismus/refractive errors, congenital heart defects, genitourinary anomalies, and epilepsy. While dysmorphic features have been described in individuals with this condition, these features are not typically distinctive enough to allow for a clinical diagnosis of SAS.
There is evidence that genetic variation may affect circulating thyroid-stimulating hormone (TSH; see 188540) levels. Deficiency in TSH can cause nongoitrous congenital hypothyroidism (see CHNG4, 275100).
Autosomal recessive protein C deficiency resulting from homozygous or compound heterozygous PROC mutations is a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia (Millar et al., 2000).
CD59-mediated hemolytic anemia with immune-mediated polyneuropathy is an autosomal recessive disorder characterized by infantile onset of a relapsing-remitting polyneuropathy, often exacerbated by infection, and manifest as hypotonia, limb muscle weakness, and hyporeflexia. Immunosuppressive treatment may result in some clinical improvement (summary by Nevo et al., 2013).
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life (summary by Wu et al., 2004 and Zhang et al., 2012). For a discussion of genetic heterogeneity of porokeratosis, see 175800.
KCNK9 imprinting syndrome is characterized by congenital central hypotonia (manifest as decreased movement, lethargy, and weak cry), severe feeding difficulties (resulting from facial weakness and poor suck), delayed development/intellectual disability, and dysmorphic manifestations. Poor feeding can cause failure to thrive during infancy unless managed appropriately. Significant dysphagia of solid foods typically persists until puberty. Intellectual disability can be severe. To date 19 individuals with a molecularly confirmed diagnosis have been reported.
Fontaine progeroid syndrome is characterized by prenatal and postnatal growth retardation, decreased subcutaneous fat tissue, sparse hair, triangular face, widely open anterior fontanel, convex and broad nasal ridge, micrognathia, craniosynostosis in some patients, and early death in many (summary by Writzl et al., 2017).
The presence of a dilated inner part of external acoustic meatus.
Developmental hypoplasia of the cochlea.
MyD88 deficiency is an inherited disorder of the immune system (primary immunodeficiency). This primary immunodeficiency affects the innate immune response, which is the body's early, nonspecific response to foreign invaders (pathogens). MyD88 deficiency leads to abnormally frequent and severe infections by a subset of bacteria known as pyogenic bacteria. (Infection with pyogenic bacteria causes the production of pus.) However, affected individuals have normal resistance to other common bacteria, viruses, fungi, and parasites. The most common infections in MyD88 deficiency are caused by the Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa bacteria. Most people with this condition have their first bacterial infection before age 2, and the infections can be life-threatening in infancy and childhood. Infections become less frequent by about age 10.Children with MyD88 deficiency develop invasive bacterial infections, which can involve the blood (septicemia), the membrane covering the brain and spinal cord (meningitis), or the joints (leading to inflammation and arthritis). Invasive infections can also cause areas of tissue breakdown and pus production (abscesses) on internal organs. In addition, affected individuals can have localized infections of the ears, nose, or throat. Although fever is a common reaction to bacterial infections, many people with MyD88 deficiency do not at first develop a high fever in response to these infections, even if the infection is severe.
Idiopathic scoliosis is a structurally fixed lateral curvature of the spine with a rotatory component. There is at least a 10 degree curvature as demonstrated by upright spine roentgenograms by the Cobb method (Weinstein, 1994). For a discussion of genetic heterogeneity of isolated scoliosis, see IS1 (181800).
This syndrome is characterised by congenital lymphoedema of the lower limbs, atrial septal defect and a characteristic facies (a round face with a prominent forehead, a flat nasal bridge with a broad nasal tip, epicanthal folds, a thin upper lip and a cleft chin). It has been described in two brothers and a sister. Transmission appears to be autosomal recessive.
A congenital developmental disorder in which the circumference of the head is smaller than normal for the person's age and sex.
A chronic loss of joint motion in metacarpophalangeal joints due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement.
STXBP1 encephalopathy with epilepsy is characterized by early-onset encephalopathy with epilepsy (i.e., moderate to severe intellectual disability, refractory seizures, and ongoing epileptiform activity). The median age of onset of seizures is six weeks (range 1 day to 13 years). Seizure types can include infantile spasms; generalized tonic-clonic, clonic, or tonic seizures; and myoclonic, focal, atonic, and absence seizures. Epilepsy syndromes can include Ohtahara syndrome, West syndrome, Lennox-Gaustaut syndrome, and Dravet syndrome (not SCN1A-related), classic Rett syndrome (not MECP2-related), and atypical Rett syndrome (not CDKL5-related). The EEG is characterized by focal epileptic activity, burst suppression, hypsarrhythmia, or generalized spike-and-slow waves. Other findings can include abnormal tone, movement disorders (especially ataxia and dystonia), and behavior disorders (including autism spectrum disorder). Feeding difficulties are common.
Reduced amount of myelin in the nervous system resulting from defective myelinogenesis in the white matter of the central nervous system.
EBSPA is an autosomal recessive genodermatosis characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. In reports of 2 consensus meetings for EB, Fine et al. (2000, 2008) considered EBSPA to be a 'basal' form of simplex EB because the electron microscopy shows that skin cleavage occurs in the lower basal level of the keratinocyte, just above the hemidesmosome. There is often decreased integration of keratin filaments with hemidesmosomes.
A rare lethal congenital abnormality that refers to the abnormal development of the capillaries around the alveoli in the lung parenchyma. It manifests as respiratory distress and persistent pulmonary hypertension in infancy.
EDAID2 is characterized by variable features of ectodermal dysplasia (e.g., hypo/anhidrosis, sparse hair, tooth anomalies) and various immunologic and infectious phenotypes of differing severity (summary by Boisson et al., 2017). Mutations in the NFKBIA gene result in functional impairment of NFKB (see 164011), a master transcription factor required for normal activation of immune responses. Interruption of NFKB signaling results in decreased production of proinflammatory cytokines and certain interferons, rendering patients susceptible to infection (McDonald et al., 2007). For discussion of genetic heterogeneity of ectodermal dysplasia and immune deficiency, see 300291.
Glucose is the major source of energy in humans, with levels in vivo determined by a balance of glucose absorption via the gut, production primarily by the liver, and utilization by both insulin-sensitive and insulin-insensitive tissues. Blood and plasma fasting glucose levels are tightly regulated within a narrow physiologic range by a feedback mechanism that targets a particular fasting glucose set point for each individual. Within healthy, nondiabetic populations there is substantial variation in fasting glucose levels. Approximately one-third of this variation is genetic. Disruption of normal glucose homeostasis and substantial elevations of fasting glucose are hallmarks of type 2 diabetes (T2D) and typically result from sustained reduction in pancreatic beta-cell function and insulin secretion (summary by Chen et al., 2008 and Prokopenko et al., 2009). Genetic Heterogeneity Genetic loci influencing fasting plasma glucose have been identified on 2q24-q32 (FGQTL1), related to single-nucleotide polymorphisms (SNPs) in the vicinity of the G6PC2 gene (608058); on 7p15-p13 (FGQTL2; 613219), related to SNPs in the vicinity of the glucokinase gene (GCK; 138079); on 11q21-q22 (FGQTL3; 613233), related to SNPs in the vicinity of the MTNR1B gene (600804); on 7p21.2 (FGQTL4; 613462), in the vicinity of the DGKB gene (604070); on 2p23.3-p23.2 (FGQTL5; 613463) due to variation in the GCKR gene (600842); and on 3q21 (FGQTL6; 613460), in the vicinity of the ADCY5 gene (600293). See 613219 for a discussion of birth weight as a quantitative trait, another glycemic-influenced trait with an effect on T2D risk. See also 606035 for a discussion of a fasting insulin quantitative trait locus on chromosome 6q22-q24.
Multiple familial trichoepithelioma (MFT) is an autosomal dominant disorder of skin appendage tumors characterized by the appearance of trichoepitheliomas. See also MFT1 (601606), which is caused by mutations in the CYLD gene (605018) on chromosome 16q12-q13.
Renal hypouricemia is a common inherited disorder characterized by impaired renal urate reabsorption and subsequent low serum urate levels. It may be associated with severe complications such as exercise-induced acute renal failure (EIARF) and nephrolithiasis (summary by Matsuo et al., 2008). For additional phenotypic information and a discussion of genetic heterogeneity of renal hypouricemia, see RHUC1 (220150).
TARDBP-related amyotrophic lateral sclerosis (TARDBP-related ALS) is characterized by upper motor neuron (UMN) and lower motor neuron (LMN) disease that appears indistinguishable from ALS of other known and unknown causes based on gender ratio, age of onset, symptom distribution, and severity of disease. The male to female ratio is 1.6 to 1. Mean age of onset is 54 ± 12 years. UMN manifestations can include stiffness, spasticity, hyperreflexia, and pseudobulbar affect; LMN manifestations often include weakness accompanied by muscle atrophy, fasciculations, and cramping. Limb onset occurs in 80% and bulbar onset in 20%. Affected individuals typically succumb to respiratory failure when phrenic and thoracic motor neurons become severely involved.
A very rare movement disorder with characteristics of early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism. Disease presents in infancy to late childhood with one of two possible phenotypes: either generalised dystonia or dystonia-parkinsonism not responsive to L-Dopa. Dystonia usually starts in one limb, becomes generalised and mainly affects the trunk, neck and oromandibular muscles. Motor and speech developmental delays were also reported. The phenotypic spectrum of this disease is still being determined. Caused by mutations in the protein kinase, interferon-inducible double stranded RNA dependent activator (PRKRA) gene, located on chromosome 2q31.2. Inherited in an autosomal recessive manner.
Recombination plays a crucial role in meiosis, ensuring the proper segregation of chromosomes. Linkage disequilibrium (LD) and sperm typing studies suggested that recombination rates vary tremendously across the human genome, with most events occurring in narrow hotspots (Coop et al., 2008). To examine variation in fine-scale recombination patterns among individuals, Coop et al. (2008) used dense genomewide nucleotide polymorphism data collected in nuclear families to localize crossovers with high spatial resolution. This analysis revealed that overall recombination hotspot usage is similar in males and females, with individual hotspots often active in both sexes. Across the genome, roughly 60% of crossovers occurred in hotspots inferred from LD studies (on chromosomes 17, 19, 10, and 11). Notably, however, Coop et al. (2008) found extensive and heritable variation among both males and females in the proportion of crossovers occurring in these hotspots.
Primary coenzyme Q10 (CoQ10) deficiency is usually associated with multisystem involvement, including neurologic manifestations such as fatal neonatal encephalopathy with hypotonia; a late-onset slowly progressive multiple-system atrophy-like phenotype (neurodegeneration with autonomic failure and various combinations of parkinsonism and cerebellar ataxia, and pyramidal dysfunction); and dystonia, spasticity, seizures, and intellectual disability. Steroid-resistant nephrotic syndrome (SRNS), the hallmark renal manifestation, is often the initial manifestation either as isolated renal involvement that progresses to end-stage renal disease (ESRD), or associated with encephalopathy (seizures, stroke-like episodes, severe neurologic impairment) resulting in early death. Hypertrophic cardiomyopathy (HCM), retinopathy or optic atrophy, and sensorineural hearing loss can also be seen.
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. Type I CDGs comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein. These disorders can be identified by a characteristic abnormal isoelectric focusing profile of plasma transferrin (Leroy, 2006). For a discussion of the classification of CDGs, see CDG1A (212065).
Individuals with the 15q13.3 microdeletion are at increased risk for a wide range of clinical manifestations including intellectual disability, seizures, autism spectrum disorders, and schizophrenia; however, the microdeletion itself does not appear to lead to a clinically recognizable syndrome and a subset of persons with the deletion have no obvious clinical findings. Behavioral problems are common and mainly comprise poor attention span, hyperactivity, mood disorder, and aggressive and/or impulsive behavior. Intellectual disability, observed in about half of the individuals with this recurrent deletion, is usually mild but can be moderate to severe.
A hemisacral defect involving the sacral vertebrae S2 to S5. In hemisacrum, the first sacral vertebra is intact and there is agenesis involving only S2-S5.
DFNA2 nonsyndromic hearing loss is characterized by symmetric, predominantly high-frequency sensorineural hearing loss (SNHL) that is progressive across all frequencies. At younger ages, hearing loss tends to be mild in the low frequencies and moderate in the high frequencies; in older persons, the hearing loss is moderate in the low frequencies and severe to profound in the high frequencies. Although the hearing impairment is often detected during routine hearing assessment of a school-age child, it is likely that hearing is impaired from birth, especially at high frequencies. Most affected persons initially require hearing aids to assist with sound amplification between ages ten and 40 years. By age 70 years, all persons with DFNA2 nonsyndromic hearing loss have severe-to-profound hearing impairment.
A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria. [HPO:probinson]
A persistent left superior vena cava (PLSVC) that drains into the right atrium via the coronary sinus. This is the case in 80-92% of cases of PLSVC and results in no hemodynamic consequence.
Hereditary primary lymphedema is caused by anatomic or functional defects in the lymphatic system, resulting in chronic swelling of body parts. There may be accompanying nail and skin changes, such as nail dysplasia or papillomatosis. Onset is usually at birth or in early childhood but can occur later, and the severity is variable (summary by Gordon et al., 2013 and Balboa-Beltran et al., 2014). For a discussion of genetic heterogeneity of lymphatic malformation, see 153100.
Episodic ataxia is a group of related conditions that affect the nervous system and cause problems with movement. People with episodic ataxia have recurrent episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraine headaches, blurred or double vision, slurred speech, and ringing in the ears (tinnitus). Seizures, muscle weakness, and paralysis affecting one side of the body (hemiplegia) may also occur during attacks. Additionally, some affected individuals have a muscle abnormality called myokymia during or between episodes. This abnormality can cause muscle cramping, stiffness, and continuous, fine muscle twitching that appears as rippling under the skin.Episodes of ataxia and other symptoms can begin anytime from early childhood to adulthood. They can be triggered by environmental factors such as emotional stress, caffeine, alcohol, certain medications, physical activity, and illness. The frequency of attacks ranges from several per day to one or two per year. Between episodes, some affected individuals continue to experience ataxia, which may worsen over time, as well as involuntary eye movements called nystagmus.Researchers have identified at least seven types of episodic ataxia, designated type 1 through type 7. The types are distinguished by their pattern of signs and symptoms, age of onset, length of attacks, and, when known, genetic cause.
Pulmonary alveolar proteinosis (PAP) is a rare lung disorder in which surfactant-derived lipoproteins accumulate excessively within pulmonary alveoli, causing severe respiratory distress. Three forms of PAP have been described: hereditary (usually congenital), secondary, and acquired. Hereditary PAP is associated with mutations in the CSF2RA gene or in genes encoding surfactant proteins. Secondary PAP develops in conditions in which there are reduced numbers or functional impairment of alveolar macrophages and is associated with inhalation of inorganic dust (silica) or toxic fumes, hematologic malignancies, pharmacologic immunosuppression, infections, and impaired CSF2RB (138960) expression. Acquired PAP (610910), the most common form, usually occurs in adults and is caused by neutralizing autoantibodies to CSF2 (138960) (Martinez-Moczygemba et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of congenital pulmonary surfactant metabolism dysfunction, see SMDP1 (265120).
X-linked protoporphyria (XLP) is characterized in affected males by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within minutes of sun/light exposure and may be accompanied by swelling and redness. Vesicular lesions are uncommon. Pain, which may seem out of proportion to the visible skin lesions, may persist for hours or days after the initial phototoxic reaction. Photosensitivity usually remains for life. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. An unknown proportion of individuals with XLP develop liver disease. Except for those with advanced liver disease, life expectancy is not reduced. The phenotype in heterozygous females ranges from asymptomatic to as severe as affected males.
Syndrome with the association of toe syndactyly, facial dysmorphism including telecanthus and a broad nasal tip, urogenital malformations and anal atresia. Around ten cases have been reported so far. The syndrome is caused by mutations in the FAM58A gene (located on the X chromosome) encoding a protein of unknown function.
Hypospadias is a common congenital malformation of the penis, affecting approximately 1 in 750 births in Europe. Due to developmental arrest of urethral fusion, the urethral opening is displaced along the ventral side of the penis. The opening can be located glandular, penile, or even more posterior in the scrotum or perineum. Although most children with this condition undergo surgery in their second year of life, serious medical, social, and sexual problems may still exist later in life (summary by van der Zanden et al., 2011). Hypospadias is a feature of several syndromic disorders, including the androgen insensitivity syndrome (300068) and Opitz syndrome (300000). Genetic Heterogeneity of Hypospadias See also HYSP2 (300758), caused by mutation in the MAMLD1 gene (300120) on chromosome Xq28; HYSP3 (146450), a familial form which has been mapped to chromosome 7q32.2-q36.1; and HYSP4 (300856), a susceptibility locus mapped to chromosome Xp11.22 and associated with variation in the DGKK gene (300837).
Christianson syndrome (referred to as CS in this GeneReview), an X-linked disorder, is characterized in males by cognitive dysfunction, behavioral disorder, and neurologic findings (e.g., seizures, ataxia, postnatal microcephaly, and eye movement abnormalities). Males with CS typically present with global developmental delay, later meeting criteria for severe intellectual disability (ID). Behaviorally, autism spectrum disorder and hyperactivity are common, and may resemble the behaviors observed in Angelman syndrome. Hypotonia and oropharyngeal dysphagia in infancy may result in failure to thrive. Seizures, typically beginning before age three years, can include infantile spasms and tonic, tonic-clonic, myoclonic, and atonic seizures. Subsequently, regression (e.g., loss of ambulation and ability to feed independently) may occur. Manifestations in heterozygous females range from asymptomatic to mild ID and/or behavioral issues.
Thrombocytopenia-3 is an autosomal recessive hematologic disorder characterized by onset of small-platelet thrombocytopenia in infancy. Patients may show variable bleeding tendency, manifest as petechiae, epistaxis, or heavy menstrual bleeding (summary by Levin et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of thrombocytopenia, see 313900.
A partial dislocation of the intervertebral joint between the second and third cervical vertebrae.
Missing ulna bone associated with congenital failure of development.
Missing humerus bone associated with congenital failure of development.
Combined pituitary hormone deficiency is a condition that causes a shortage (deficiency) of several hormones produced by the pituitary gland, which is located at the base of the brain. A lack of these hormones may affect the development of many parts of the body. The first signs of this condition include a failure to grow at the expected rate and short stature that usually becomes apparent in early childhood.People with combined pituitary hormone deficiency may have hypothyroidism, which is underactivity of the butterfly-shaped thyroid gland in the lower neck. Hypothyroidism can cause many symptoms, including weight gain and fatigue. Other features of combined pituitary hormone deficiency include delayed or absent puberty and lack the ability to have biological children (infertility). The condition can also be associated with a deficiency of the hormone cortisol. Cortisol deficiency can impair the body's immune system, causing individuals to be more susceptible to infection.Rarely, people with combined pituitary hormone deficiency have intellectual disability; a short, stiff neck; or underdeveloped optic nerves, which carry visual information from the eyes to the brain.
A form of primary hypertrophic osteoarthropathy with characteristics of delayed closure of the cranial sutures and fontanelles, digital clubbing, arthropathy, and periostosis. To date, about 30 cases have been reported. May also be associated with congenital heart disease. It is caused by mutations in the HPGD gene (4q33-q34) and is inherited as an autosomal recessive trait.
Congenital arthrogryposis with anterior horn cell disease (CAAHD) is an autosomal recessive neuromuscular disorder with highly variable severity. Affected individuals are usually noted to have contractures in utero on prenatal ultrasound studies, and present at birth with generalized contractures manifest as arthrogryposis multiplex congenita (AMC). Patients have severe hypotonia with respiratory insufficiency, often resulting in death in infancy or early childhood. Some patients may survive into later childhood with supportive care, but may be unable to walk or sit independently due to a combination of muscle weakness and contractures. Cognition may be normal. The disorder also includes multiple congenital anomalies associated with AMC and hypotonia, including high-arched palate, myopathic facies, and bulbar weakness. Neuropathologic studies demonstrate severe loss of anterior horn cells in the spinal cord, as well as diffuse motor neuron axonopathy (summary by Smith et al., 2017 and Tan et al., 2017). Distinction from Lethal Congenital Contracture Syndrome 1 Biallelic mutation in the GLE1 gene can also cause LCCS1, which is lethal in utero. However, distinguishing between LCCS1 and CAAHD is controversial. Smith et al. (2017) suggested that differentiating between the 2 disorders has limited utility, and that they may represent a genotype/phenotype correlation rather than 2 different disease entities. In contrast, Said et al. (2017) concluded that LCCS1 represents a distinct clinical entity in which all affected individuals die prenatally and exhibit no fetal movements. Vuopala et al. (1995) differentiated CAAHD from LCCS1, noting that both are prevalent in Finland. LCCS1 is always fatal during the fetal period, presenting with severe hydrops and intrauterine growth retardation. In LCCS1, the spinal cord is macroscopically thinned because of an early reduction of the anterior horn and a paucity of anterior horn cells. The skeletal muscles are extremely hypoplastic, even difficult to locate. Infants with CAAHD survive longer than those with LCCS1, and when present, hydrops and intrauterine growth retardation are mild. The macroscopic findings of the central nervous system and skeletal muscles are closer to normal, although microscopic analysis also shows degeneration of anterior horn cells. In addition, birthplaces of ancestors of affected individuals do not show clustering in the northeast part of Finland, as is the case with LCCS1.
Dilated cardiomyopathy-1Y (CMD1Y) is characterized by severe progressive cardiac failure, resulting in death in the third to sixth decades of life in some patients. Electron microscopy shows an abnormal sarcomere structure (Olson et al., 2001). In left ventricular noncompaction-9 (LVNC9), patients may present with cardiac failure or may be asymptomatic. Echocardiography shows noncompaction of the apex and midventricular wall of the left ventricle (Probst et al., 2011). Some patients also exhibit Ebstein anomaly of the tricuspid valve (Kelle et al., 2016) and some have mitral valve insufficiency (Nijak et al., 2018).
Temple-Baraitser syndrome is a rare developmental disorder characterized by severe mental retardation and anomalies of the first ray of the upper and lower limbs with absence/hypoplasia of the nails. Most patients also have seizures; various dysmorphic facial features have been reported (summary by Jacquinet et al., 2010).
An autosomal recessive condition characterized by female to male sex reversal and kidney, adrenal, and lung dysgenesis, due to mutation(s) in the WNT4 gene.
Elliptocytosis is a hematologic disorder characterized by elliptically shaped erythrocytes and a variable degree of hemolytic anemia. Usually inherited as an autosomal dominant trait, elliptocytosis results from mutation in any one of several genes encoding proteins of the red cell membrane skeleton (summary by McGuire et al., 1988). Genetic Heterogeneity of Elliptocytosis Elliptocytosis-2 (130600) is caused by mutation in the SPTA1 gene (182860). Elliptocytosis-3 (617948) is caused by mutation in the SPTB gene (182870). Elliptocytosis-4 (166900), also known as Southeast Asian ovalocytosis, is caused by mutation in the SLC4A1 gene (109270). Also see pyropoikilocytosis (266140). See Delaunay (2007) for a discussion of the molecular basis of hereditary red cell membrane disorders.
Vibration felt by examiner on the surface of the body
Spastic paraplegia-43 (SPG43) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive spasticity affecting the lower and upper limbs (summary by Meilleur et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Familial progressive hyperpigmentation (FPH) is a rare autosomal dominant disorder characterized by patches of hyperpigmentation in the skin, which are present at birth or in early infancy and increase in size and number with age (summary by Zhang et al., 2006). Also see familial progressive hyperpigmentation with or without hypopigmentation (FPHH; 145250).
Retinitis pigmentosa is characterized by constriction of the visual fields, night blindness, and fundus changes, including 'bone corpuscle' lumps of pigment. RP unassociated with other abnormalities is inherited most frequently (84%) as an autosomal recessive, next as an autosomal dominant (10%), and least frequently (6%) as an X-linked recessive in the white U.S. population (Boughman et al., 1980). For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
A piperazine derivative and PLATELET AGGREGATION INHIBITOR that is used to prevent THROMBOSIS in patients with ACUTE CORONARY SYNDROME; UNSTABLE ANGINA and MYOCARDIAL INFARCTION, as well as in those undergoing PERCUTANEOUS CORONARY INTERVENTIONS.
The presence of ovarian and testicular tissue in the an individual with 46,XY karyotype. The anatomical expression of this condition is variable.
A calcium salt formulation of gemcabene, a dialkyl ether dicarboxylic acid with antihyperlipidemic activity.
A lipophilic, unsaturated fatty acid ester derivative of gemcitabine (dFdC), an antimetabolite deoxynucleoside analogue, with potential antineoplastic activity. Upon hydrolysis intracellularly by esterases, the prodrug gemcitabine is converted into the active metabolites difluorodeoxycytidine di- and tri-phosphate (dFdCDP and dFdCTP) by deoxycytidine kinase. dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis; dFdCTP is incorporated into DNA, resulting in DNA strand termination and apoptosis. Due to its lipophilicity, gemcitabine 5'-elaidic acid ester exhibits an increased cellular uptake and accumulation, resulting in an increased conversion to active metabolites, compared to gemcitabine. In addition, this formulation of gemcitabine may be less susceptible to deamination and deactivation by deoxycytidine deaminase.
A second-generation, sulfonamide urea derivative with antihyperglycemic activity. Glidazamide's hypoglycemic effect is inferior to that of glicaramide.
A glycosylated form of a recombinant agent that is chemically identical to or similar to endogenous human granulocyte colony-stimulating factor (G-CSF) and is produced using transgenic biotechnology. Transgenic hens carrying recombinant human G-CSF cDNA express the naturally glycosylated recombinant human protein in egg albumen from which glycosylated recombinant human G-CSF AVI-014 is isolated. Produced endogenously by monocytes, fibroblasts, and endothelial cells, G-CSF binds to and activates specific cell surface receptors, stimulating neutrophil progenitor proliferation and differentiation and selected neutrophil functions.
A glycosylated recombinant protein which is chemically identical to or similar to endogenous human interleukin-7 (IL-7) with hematopoietic and immunopotentiating activities. Naturally produced by bone marrow, thymic stromal, and spleen cells, the cytokine interleukin-7 is a hematopoietic growth factor for progenitor B cells and T cells, stimulating proliferation and differentiation of mature T-cells and natural killer (NK) cells. As with glycosylated endogenous proteins, glycosylation of recombinant proteins may fundamentally affect their biological activity, function, clearance from circulation, and antigenicity; glycosylation of recombinant proteins that are chemically idenitical to or similar to endogenous proteins may render protein structures and biological activities that are more similar to those of glycosylated endogenous proteins.
A multi-targeted, small-molecule inhibitor of histone deacetylase (HDAC), epidermal growth factor receptor tyrosine kinase (EGFR/ErbB1), and human epidermal growth factor receptor 2 tyrosine kinase (HER2/neu or ErbB2) with potential antineoplastic activity. HDAC/EGFR/HER2 inhibitor CUDC-101 inhibits the activity of these three enzymes but the exact mechanism of action is presently unknown. This agent may help overcome resistance to inhibition of EGFR and Her2 through a simultaneous, synergistic inhibition of EGFR, Her2, and HDAC.
A cancer vaccine containing three HLA-A*0201-restricted peptide epitopes with potential immunostimulatory, antiangiogenic, and antitumor activities. Vaccine peptide epitopes are derived from the tumor associated antigen (TAA) URLC (up-regulated in lung cancer 10) and vascular endothelial growth factor receptors (VEGFR) 1 and 2. Upon administration, HLA-A*0201-restricted URLC10-VEGFR1-VEGFR2 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against URLC10-expressing tumor cells and the tumor microvasculature expressing VEGFR 1 and 2 peptides; this may result in tumor cell lysis, the inhibition of tumor angiogenesis, and decreased tumor growth. HLA-A*0201 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*0201 may improve antigenic peptide immunogenicity.
A cancer vaccine containing two HLA-A*0201-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from: vascular endothelial growth factor receptors (VEGFR) 1 and 2. Upon administration, HLA-A*0201-restricted VEGFR1-VEGFR2 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing VEGFR 1 and 2 peptides, resulting in tumor cell lysis and decreased tumor growth. HLA-A*0201 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*0201 may improve antigenic peptide immunogenicity.
A cancer vaccine containing an HLA-A*0201-restricted vascular endothelial growth factor receptor 1 (VEGFR1) peptide (sequence: TLFWLLLTL) with potential immunostimulatory and antitumor activities. Upon administration, HLA-A*0201-restricted VEGFR1-derived peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing VEGFR1, resulting in tumor cell lysis and decreased tumor growth. HLA-A*0201 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*0201 may improve antigenic peptide immunogenicity.
A cancer vaccine containing five HLA-A*2402-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from IGF II mRNA binding protein 3 (KOC1); TTK protein kinase (TTK); URLC10 (up-regulated lung cancer 10); DEP domain containing 1 (DEPDC1); and M phase phosphoprotein 1 (MPHOSPH1). Upon administration, HLA-A*2404-restricted KOC1-TTK-CO16-DEPDC1-MPHOSPH1 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing KOC1, TTK, CO16, DEPDC1 and MPHOSPH1 peptides, resulting in tumor cell lysis and decreased tumor growth. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A cancer vaccine containing four HLA-A*2402-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from URLC10 (up-regulated lung cancer 10 or CO16); KOC1 (IGF II mRNA Binding Protein 3); and vascular endothelial growth factor receptors (VEGFRs) 1 and 2. Upon administration, this multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against URL10-, KOC1-, VEGFR1- and VEGFR2-expressing tumor cells, resulting in tumor cell lysis and decreased tumor growth. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A cancer vaccine containing three HLA-A*2402-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from URLC10 (up-regulated lung cancer 10); TTK (TTK protein kinase); and KOC1 (IGF II mRNA Binding Protein 3). Upon administration, URLC10-TTK-KOC1 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing URLC10, TTK and KOC1 peptides, resulting in tumor cell lysis and decreased tumor growth. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A cancer vaccine containing the HLA-A*2402-restricted vascular endothelial growth factor receptor 1 (VEGFR1) peptide epitope with potential immunostimulatory and antitumor activities. Upon administration, HLA-A*2402-restricted VEGFR1 peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing VEGFR 1 peptide, resulting in tumor cell lysis and decreased tumor growth. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A cancer vaccine containing four HLA-A*2402-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from ring finger protein 43 (RNF43); translocase of outer mitochondrial membrane 34 (TOMM34); and vascular endothelial growth factor receptors (VEGFR) 1 and 2. Upon administration, HLA-A*2404-restricted RNF43-TOMM34-VEGFR1-VEGFR2 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing RNF43, TOMM34, and VEGFR 1 and 2 peptides, resulting in tumor cell lysis and decreased tumor growth. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
Any agent that inhibits functions of heat shock proteins (Hsp). Hsps are a group of homodimeric molecular chaperones that interact with a diverse group of proteins, assisting in their folding and in the elimination of any misfolded or damaged molecules. Although transiently expressed during cell cycle in normal cells, Hsps are constitutively elevated in various types of cancer which raises the apoptosis threshold of these tumor cells and provides protection against cytotoxic agents. Hsp inhibitors may destabilize, and facilitate degradation of proto-oncoproteins leading to reversal of apoptosis regulation and cell death.
A cancer vaccine directed against human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, with potential immunostimulating and antineoplastic activities. Upon administration, hTERT vaccine V934/V935 may elicit a cytotoxic T cell (CTL) response against telomerase-expressing tumor cells, which may result in tumor cell death. Telomerase is involved in the restoration and maintenance of telomere length and so the functional lifespan of cells. Abnormally reactivated in tumorigenesis, telomerase is expressed in the majority of human cancer cells but is not expressed or is expressed at very low levels in normal cells.
An inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. mTOR kinase inhibitor AZD8055 inhibits the serine/threonine kinase activity of mTOR, resulting in decreased expression of mRNAs necessary for cell cycle progression, which may induce cell cycle arrest and tumor cell apoptosis. mTOR phosphorylates transcription factors, such as S6K1 and 4E-BP1, which stimulate protein synthesis and regulate cell growth, proliferation, motility, and survival.
A cytogenetic finding indicating that the translocation (14;18) is present in cells.
An orally bioavailable formulation of the ansamycin derivative 17-amino-17-demethoxygeldanamycin (17-AG) with potential antineoplastic activity. Oral Hsp90 inhibitor IPI-493 binds to and inhibits Hsp90, which may result the in growth inhibition in sensitive tumor cell populations. Hsp90, a 90 kDa molecular chaperone, may be highly expressed in tumor cells, playing a key role in the conformational maturation, stability and function of other substrate or ""client"" proteins within the cell; many of these client proteins are involved in signal transduction, cell cycle regulation and apoptosis, and may include kinases, transcription factors and hormone receptors.
An orally bioavailable, ATP-competitive, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor XL888 specifically binds to Hsp90, inhibiting its chaperone function and promoting the proteasomal degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival; inhibition of tumor cell proliferation may result. Hsp90, a chaperone complex protein upregulated in a variety of tumor cell types, regulates the folding and degradation of many oncogenic signaling proteins, including Her-2 and Met.
A human monoclonal antibody (B11) directed against the mannose receptor and linked to the beta-subunit of human chorionic gonadotropin (hCG beta) with potential immunostimulating and antineoplastic activities. The monoclonal antibody moiety of human monoclonal antibody B11-hCG beta fusion protein CDX-1307 binds to mannose receptors on antigen presenting cells (APCs), including human dendritic cells (DCs) and macrophages. Upon internalization and processing, APCs present the processed hCG beta antigen on their cell surfaces, which may initiate an antibody-dependent cell-mediated cytotoxicity (ADCC) response against hCG beta-expressing tumor cells. The tumor-associated antigen (TAA) hCG beta is selectively overexpressed by a number of tumors including breast, colorectal, pancreatic, bladder and ovarian tumors; its expression may correlate with the stage of disease.
A hydrazinopyridazine-based diuretic with antihypertensive activity. Hydracarbazine is no longer marketed.
A B-cell acute leukemia characterized by the presence of lymphoblasts which contain more than 50 and usually less than 66 chromosomes. It is commonly seen in children and rarely in adults. It has a favorable clinical outcome.
A B-cell acute leukemia characterized by the presence of lymphoblasts which contain less than 46 chromosomes. It occurs in both children and adults. It has an unfavorable clinical outcome.
The hydrochloride salt of a small-molecule inhibitor of IAP (Inhibitor of Apoptosis Protein) family proteins with potential antineoplastic activity. IAP inhibitor HGS1029 selectively inhibits the biological activity of IAP proteins, which may restore apoptotic signaling pathways; this agent may work synergistically with cytotoxic drugs to overcome tumor cell resistance to apoptosis. IAPs are overexpressed by many cancer cell types, suppressing apoptosis by binding and inhibiting active caspases-3, -7 and -9 via their BIR (baculoviral lAP repeat) domains.
A multi-peptide cancer vaccine with potential immunostimulating and antineoplastic activities. IMT-1012 immunotherapeutic vaccine contains twelve different synthetic peptides or tumor associated antigens (TAAs), including cyclin I (CCNI), cyclin-dependent kinase CDC2, EDDRI and TACE/ADAM17, each of which is involved in a different pathway associated with tumor growth, survival, and metastasis. Each antigen in the vaccine elicits a specific cytotoxic T-lymphocyte (CTL) immune response against tumor cells expressing that antigen. This multi-antigen/multi-pathway targeting strategy provides broad immunotherapeutic coverage with respect to tumor complexity and heterogeneity and may result in enhanced vaccine efficacy.
A lipoprotein lipase (LPL) activator with antihyperlipidemic activity. Activation of LDL by ibrolipim lowers plasma triglycerides, with a concomitant elevation of high-density lipoprotein cholesterol.
Problem associated with the heart valve leaflet not closing properly.
An anhydrous formulation of indinavir, a synthetic hydroxyaminopentane amide agent that selectively inhibits the protease of both human immunodeficiency virus 1 and 2. The incorporation of a basic amine into the hydroxyethylene backbone improves its aqueous solubility and its oral bioavailability.
An acute or chronic infectious process affecting the fallopian tube. Chlamydia trachomatis, Neisseria gonorrhea, Mycoplasma, Staphylococcus, and Streptococcus are the most common causative agents.
A cancer vaccine consisting of allogeneic neuroblastoma tumor cells have been genetically modified to secrete the human cytokine interleukin-2 (IL-2) and the human chemokine lymphotactin (Lptn) with potential immunostimulating and antineoplastic activities. Upon administration, IL-2 and Lptn are secreted by the IL-2/Lptn gene-modified allogeneic neuroblastoma tumor cell vaccine, potentially enhancing the cytotoxic T lymphocyte (CTL) response elicited by vaccine neuroblastoma tumor-associated antigens (TAAs) against host neuroblastoma tumor cells. Produced by activated progenitor T cells, Lptn belongs to the C chemokine subfamily and is a potent chemotactic factor for lymphocytes; IL-2 stimulates natural killer (NK) cells and may enhance a vaccine-elicited CTL immune response against tumor cells.
A necrotic process involving the intestinal wall.
The mesylate salt form of ispinesib, a synthetic small molecule, derived from quinazolinone, and kinesin spindle protein (KSP) inhibitor, with antineoplastic activity. Ispinesib selectively inhibits KSP and prevents its binding to microtubules, resulting in inhibition of mitotic spindle assembly, induction of cell cycle arrest during the M-phase, and cell death in tumor cells that are actively dividing.
A benign or malignant tumor of the liver composed of hepatic stellate cells.
The sulfate salt form of kanamycin A, the major component of the kanamycin complex, an aminoglycoside antibiotic isolated from Streptomyces kanamyceticus, with antibacterial activity.
A folic acid antagonist and mammalian dihydrofolate reductase inhibitor with antineoplastic activity. Ketotrexate inhibits dihydrofolate reductase, an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid which is essential for the synthesis of purine nucleotides and thymidylate. By depleting tetrahydrofolic acid availability, DNA synthesis is halted.
A classification of myocardial infarction characterized by an absence of rales over the lung fields and an absence of S3.
A classification of myocardial infarction characterized by rales over 50% or less of the lung fields or the presence of an S3.
A classification of myocardial infarction characterized by rales over more than 50% of the lung fields.
A classification of myocardial infarction characterized by cardiogenic shock; an event with systolic BP less than 90 mmHg for greater than 30 minutes, not responsive to fluid resuscitation alone, and felt to be secondary to cardiac dysfunction. Associated signs of hypoperfusion (cool and clammy skin, oliguria, or altered sensorium) or a cardiac index of less than 2.2 L/min/m2 are present. This includes when the systolic BP increases to greater than 90 mmHg in response to inotropic agents in less than 1 hour.)
A whole-cell cancer vaccine, containing human acute myeloid leukemic (AML) blasts that have been genetically engineered to express a B7.1/IIL-2 fusion protein encoded by a self-inactivating lentiviral vector (LV), with potential antineoplastic and immunomodulating activities. Upon administration, LV.IL-2/B7.1-transduced AML blast vaccine may stimulate a host cytotoxic T lymphocyte (CTL) response against AML cells. The single fusion protein encoded by the LV is postsynthetically cleaved to produce biologically active membrane-anchored B7.1 and secreted IL-2 in AML blasts; combined expression of IL-2 and the co-stimulatory molecule B7.1 by AML blasts may increase stimulation of both allogeneic and autologous cytotoxic T cells.
An indication or description of an adverse event occurrence.
The toxicity grade value of the adverse event.
An aerosol inhalation formulation containing a yeast-derived glycosylated recombinant form of human granulocyte macrophage colony stimulating factor (GM-CSF) with potential immunostimulating activity. Sargramostim binds to specific cell surface receptors, modulating the proliferation and differentiation of a variety of hematopoietic progenitor cells with some specificity towards stimulation of leukocyte production. This agent also activates neutrophils, monocytes, macrophages, and dendritic cells and promotes antigen presentation, upregulates antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated, lymphokine-activated killer cell function. Aerosol inhalation may help achieve high concentrations of sargramostim in the lung.
The time it take to eject blood from the left ventricle. Measurement begins when the aortic valve opens and ends when the aortic valve closes.
The fumarate salt of an orally-active benzimidazole derivative with potential antineoplastic activity. As a retinoic acid metabolism blocking agent (RAMBA), liarozole inhibits cytochrome P450-dependent all-trans-retinoic acid (ATRA)-4-hydroxylase, resulting in an increase in endogenous ATRA production, inhibition of cell proliferation, and induction of cell differentiation. This agent also inhibits aromatase, the enzyme that catalyzes the final, rate-limiting step in estrogen biosynthesis.
An attenuated oncolytic vaccinia virus encoding the light-emitting fusion protein Renilla luciferase-Aequorea green fluorescent protein (RUC-GFP) with potential bioluminescent and antineoplastic activities. Upon administration, light-emitting oncolytic vaccinia virus GL-ONC1 specifically enters tumor cells due to the permeable nature of the tumor vasculature. Once inside the cell, the virus replicates, resulting in tumor cell lysis and the release of mature viral particles into the tumor microenvironment. Released viral particles may then infect and destroy neighboring tumor cells. In addition, the release of tumor-associated antigens (TAAs) by lysed tumor cells into the bloodstream may activate the immune system to mount a cytotoxic T lymphocyte (CTL) response against the tumor. The expression of RUC-GFP by this agent allows for both detection and monitoring of virally infected tumor cells in vivo and vitro with luciferase-mediated bioluminescence imaging and fluorescence imaging techniques.
The acetate salt form of linaclotide, a synthetic, fourteen amino acid peptide and agonist of intestinal guanylate cyclase type C (GC-C), which is structurally related to the guanylin peptide family, with secretagogue, analgesic and laxative activities. Upon oral administration, linaclotide binds to and activates GC-C receptors located on the luminal surface of the intestinal epithelium. This increases the concentration of intracellular cyclic guanosine monophosphate (cGMP), which is derived from guanosine triphosphate (GTP). cGMP activates the cystic fibrosis transmembrane conductance regulator (CFTR) and stimulates the secretion of chloride and bicarbonate into the intestinal lumen. This promotes sodium excretion into the lumen and results in increased intestinal fluid secretion. This ultimately accelerates GI transit of intestinal contents, improves bowel movement and relieves constipation. Increased extracellular cGMP levels may also exert an antinociceptive effect, through an as of yet not fully elucidated mechanism, that may involve modulation of nociceptors found on colonic afferent pain fibers. Linaclotide is minimally absorbed from the GI tract.
A radioconjugate of synthetic active thyroid hormone, liothyronine (T3), labeled with Iodine 125. Liothyronine involves many important metabolic functions and is essential to the proper development and differentiation of all cells. I-125 liothyronine may be used in radiotherapy in thyroid cancers.
The oil extracted from the roots of Lobelia siphilitica.
A rare autosomal dominant syndrome caused by mutations in the TGFBR1 gene. It is characterized by vascular abnormalities (aortic and arterial aneurysms, aortic dissection, and tortuosity of the arteries), hypertelorism, bifid uvula, and early fusion of the skull bones.
A chromosomal aberration where there is a loss of both the short arm of chromosome 1 and the long arm of chromosome 19. This chromosomal aberration is associated with oligodendroglial tumors.
The active, acid form of lovastatin. In the body lovastatin is hydrolysed to its beta-hydroxy acid active form.
A thiazole derivative and atypical ANTIPSYCHOTIC AGENT that functions as a DOPAMINE D2 RECEPTOR ANTAGONIST; SEROTONIN 5-HT2 RECEPTOR ANTAGONIST, serotonin 5-HT7 receptor antagonist, and antagonist of the adrenergic a2A and a2C receptors, as well as a partial SEROTONIN 5-HT1A RECEPTOR AGONIST. It is used in the treatment of SCHIZOPHRENIA and BIPOLAR DISORDER.
A nutritional lipid emulsion consisting of coconut oil-derived medium chain triglycerides (MCTs), soybean oil-derived long chain triglycerides (LCT), and the fish oil-derived polyunsaturated omega-3 fatty acids. This lipid emulsion supplies essential fatty acids and calories for energy. Omega-3 fatty acids may decrease the production of certain pro-inflammatory cytokines, including interleukin 1 (IL-1), Il-6 and tumor necrosis factor (TNF). The MCTs mainly provide calories for energy. In addition to LCTs, MCTs, and omega-3 fatty acids, this lipid emulsion contains egg yolk lecithin, glycerol, and the antioxidant alpha-tocopherol (vitamin E).
A nutritional lipid emulsion consisting of both coconut oil-derived medium chain triglycerides (MCTs) and soybean oil-derived long chain triglycerides (LCTs). The LCTs in the MCT/LCT lipid emulsion supply the body with essential omega-6 fatty acids, which are needed as components of phospholipids in cell membranes and as precursors of eicosanoids. The MCTs mainly provide calories for energy. In addition to LCTs and MCTs, this lipid emulsion contains egg yolk lecithin, glycerol, and the antioxidant alpha-tocopherol (vitamin E).
An orally bioavailable inhibitor of mitogen-activated protein kinase kinase (MEK MAPK/ERK kinase) with potential antineoplastic activity. Trametinib specifically binds to and inhibits MEK 1 and 2, resulting in an inhibition of growth factor-mediated cell signaling and cellular proliferation in various cancers. MEK 1 and 2, dual specificity threonine/tyrosine kinases often upregulated in various cancer cell types, play a key role in the activation of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth.
An immunotherapy regimen containing three components: a plasmid encoding portions of the two melanoma-associated antigens Melan A (also called MART-1) and tyrosinase and two synthetic analogs of Melan-A and tyrosinase antigen epitopes with potential immunostimulating and antitumor activities. First, the plasmid is injected directly into lymph nodes in order to sensitize or prime antigen-presenting cells (APCs) and central memory T cells in lymph nodes to plasmid-expressed Melan A and tyrosinase. After several priming injections with plasmids, the Melan A and tyrosinase synthetic epitope analogs are injected directly into lymph nodes; upon binding to major histocompatibility complex (MHC) molecules on APC cell surfaces, these synthetic epitope analogs may stimulate a ""primed"" cytotoxic T lymphocyte (CTL) response against melanoma tumor cells, resulting in tumor cell lysis. Melan-A and tyrosinase are overexpressed by melanoma tumor cells.
The l-alanine ester form of estramustine, a combination of the nitrogen mustard normustine coupled via a carbamate to estradiol, with antineoplastic activity. Upon conversion of alestramustine to estramustine, estramustine binds to microtubule-associated proteins (MAPs) and beta tubulin, thereby interfering with microtubule dynamics and leading to microtubule disassembly and cell cyle arrest. Due to the estrogen moiety, this agent is able to selectively bind to and be taken up by estrogen receptor-positive cells.
A copper(l) complex used as an antiinflammatory drug and antiarthritic agent.
A preparation of cytotoxic T-lymphocytes (CTL), specifically reactive to the Epstein-Barr virus (EBV) latent membrane proteins (LMP) 1 and 2, with potential antineoplastic activity. Peripheral blood mononuclear cells (PBMC) are collected from a donor and are exposed ex vivo to dendritic cells (DCs) transfected with a replication-deficient adenovirus encoding EBV LMP1/2 to generate LMP1/2-specific CTL which are subsequently expanded. Administration of allogeneic LMP1-/LMP2- specific CTL to patients with LMP1/2-positive tumors may result in a specific CTL response against tumor cells expressing LMP1 and LMP2, resulting in cell lysis and inhibition of tumor cell proliferation. As tumor associated antigens (TAAs), LMP1 and LMP2 are expressed in various malignancies including nasopharyngeal cancer and EBV-positive Hodgkin lymphoma.
A cancer vaccine, containing human-specific large multivalent immunogens (LMIs) isolated from the membrane fraction of cells from a breast cancer cell line, with potential immunostimulatory and antineoplastic activities. Upon administration, allogeneic large multivalent immunogen breast cancer vaccine may stimulate a cytotoxic T lymphocyte (CTL) immune response against tumor cells that express the breast cancer cell-specific LMIs.
A cancer vaccine, containing human-specific large multivalent immunogen (LMI) isolated from plasma membrane fractions of the melanoma cell lines MSM-M1 and MSM-M2, with potential immunostimulating and antineoplastic activities. Upon administration, allogeneic large multivalent immunogen melanoma vaccine LP2307 may stimulate a CD8+ cytotoxic T lymphocyte (CTL) response against melanoma tumor cells that express melanoma-specific LMI.
An oral suspension containing magnesium hydroxide, aluminum hydroxide and simethicone with antacid activity. Both magnesium hydroxide and aluminum hydroxide react with excess acid in the stomach thereby neutralizing gastric acid. Simethicone, a mixture of polydimethylsiloxane and silica gel, reduces the surface tension of gas bubbles, promoting gas bubble coalescence and so intestinal gas transit and evacuation.
A malignant tumor of the liver composed of hepatic stellate cells.
Marfan syndrome caused by mutations in the TGFBR2 gene.
The orally bioavailable mesylate salt of masatinib, a multi-targeted protein tyrosine kinase inhibitor with potential antineoplastic activity. Masitinib selectively binds to and inhibits both the wild-type and mutated forms of the stem cell factor receptor (c-Kit; SCFR); platelet-derived growth factor receptor (PDGFR); fibroblast growth factor receptor 3 (FGFR3); and, to a lesser extent, focal adhesion kinase (FAK). As a consequence, tumor cell proliferation may be inhibited in cancer cell types that overexpress these receptor tyrosine kinases (RTKs).
An immunoconjugate consisting of a monoclonal antibody directed against a highly-expressed myeloma cell surface antigen covalently attached to the maytansinoid DM4, a derivative of the cytotoxic agent maytansine (DM1), with potential antineoplastic activity. Anti-myeloma cell surface antigen immunoconjugate BT-062 binds to an unspecified cell surface antigen highly expressed on myeloma cells; upon internalization the DM4 moiety is released, binding to tubulin and disrupting microtubule assembly/disassembly dynamics, which may result in the inhibition of cell division and cell growth of myeloma tumor cells.
A cell-based cancer vaccine consisting of autologous dendritic cells (DCs) pulsed with mesothelioma tumor lysate with potential immunostimulating and antineoplastic activities. Upon administration, mesothelioma tumor lysate-pulsed autologous dendritic cell vaccine may stimulate the host immune system to mount a specific cytotoxic T lymphocyte (CTL) response against mesothelioma tumor cells, resulting in tumor cell lysis.
A cancer vaccine derived from two gentically modified human melanoma cell lines with potential antineoplastic activity. Allogeneic melanoma vaccine AGI-101H consists of a 1:1 mixture of cells from two genetically modified human melanoma cell lines, designated as Mich1H6 and Mich2H6, that have been gamma-irradiated to render the cells non-proliferative. Upon administration, this vaccine may stimulate a cytotoxic immune response against melanoma tumor cells.
The benzoate salt form of alogliptin, a selective, orally bioavailable, pyrimidinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. In addition to its effect on glucose levels, alogliptin may inhibit inflammatory responses by preventing the toll-like receptor 4 (TLR-4)-mediated formation of proinflammatory cytokines.
A preparation of glycosphingolipids (GSL), containing the disaccharide epitope galactose-alpha-1,3-galactose (alpha-Gal), with potential antineoplastic activity. Upon intratumoral injection, alpha-Gal glycosphingolipids may stimulate the immune system to mount complement-mediated cytotoxicity (CMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) responses against alpha-Gal GSL, which may result in tumor cell death; these responses involve natural anti-alpha-Gal immunoglobulins (Igs). As antibodies that occur naturally due to sensitization to alpha-Gal present on symbiotic bacterial flora, anti-alpha-Gal Igs are present in unusually high amounts in human sera. GSL represent a glycolipid subtype containing the amino alcohol sphingosine; tumor-associated GSL antigens contain various oligosaccharide residues.
A cancer vaccine comprised of autologous dendritic cells (DCs) pulsed with the marine sponge glycolipid alpha-galactosylceramide (alpha-GalCer) with potential immunostimulatory and antimetastatic activities. Upon administration, alpha-galactosylceramide-pulsed autologous dendritic cells may result in the activation and proliferation of a subset of endogenous natural killer T (NKT) cells, B cells, and CD4+ and CD8+ T cells, and the production of interferon-gamma and interleukin-12; these cascade events may result in a T helper-1 cell-biased proinflammatory antitumor immune response. The NKT cell ligand alpha-GalCer was originally isolated from the marine sponge Agelas mauritianusis.
The hydrochloride salt of alvespimycin, an analogue of the antineoplastic benzoquinone antibiotic geldanamycin. Alvespimycin binds to HSP90, a chaperone protein that aids in the assembly, maturation and folding of proteins. Subsequently, the function of Hsp90 is inhibited, leading to the degradation and depletion of its client proteins such as kinases and transcription factors involved with cell cycle regulation and signal transduction.
A triazine-based diuretic agent. Amanozine is structurally similar to the diuretic agent chlorazanil.
The tetrahydrate and chloride salt form of ambenonium, a bisquaternary ammonium alcohol with parasympathomimetic activity. The positive charge of ambenonium allows it to act as an acetylcholinesterase inhibitor by binding to the anionic site at the reactive center of acetylcholinesterase, preventing the breakdown of acetylcholine and producing an indirect cholinomimetic effect at both nicotinic and muscarinic receptors. Ambenonium also has direct agonist activity at nicotinic receptors, potentiating the cholinomimetic effect at the neuromuscular junction.
The hydrochloride salt form of amustaline, a quinacrine mustard compound with potential antineoplastic activity. Amustaline binds to, intercalates and crosslinks DNA and RNA. This agent is mainly used for ex vivo purposes, specifically for the inactivation of pathogens such as viruses, protozoa and bacteria in red blood cells (RBCs).
A synthetic non-cardiotoxic analogue of the anthracycline antibiotic doxorubicin with potential antineoplastic activity. Anthracycline analogue GPX-150 intercalates DNA and impedes the activity of topoisomerase II, inducing single and double-stranded breaks in DNA; inhibiting DNA replication and/or repair, transcription, and protein synthesis; and activating tumor cell apoptosis.
Any monoclonal antibody directed against the alpha subunit of the human interleukin 2 receptor.
A population of autologous tumor infiltrating lymphocytes (TIL) transduced with a retroviral vector encoding the chimeric gene IgCD28TCR with potential immunostimulating and antineoplastic activities. The chimeric IgCD28TCR gene consists of portions of CD28, the zeta chain of the T-cell receptor (TCRzeta), and a single chain antibody domain (sFv) specific for the tumor-associated antigen CEA. Upon administration, these gene-modified TIL bind to tumor cells expressing CEA, which may result in activation and proliferation of TIL and an enhanced cytotoxic T-lymphocyte (CTL) response against CEA-expressing tumor cells. CEA may be overexpressed in various gastrointestinal and breast cancers. CD28, a T-cell surface-associated co-stimulatory molecule, is required for full T-cell activation, proliferation, and survival; expression of the CD28 fragment in this chimeric gene construct may impede activation-induced cell death (AICD) of TIL.
Autologous human peripheral blood lymphocytes (PBLs), transduced with a retroviral vector encoding both the alpha and beta chains of a T cell receptor (TCR) specific for the carcinoembryonic antigen (CEA), with potential immunostimulating and antineoplastic activities. After transduction, expansion in culture, and reintroduction into the patient, anti-CEA TCR retroviral vector-transduced autologous lymphocytes bind to tumor cells expressing CEA, which may result in cytokine expression, activation and proliferation of T-cells, and a specific cytotoxic T-lymphocyte (CTL) response against CEA-expressing tumor cells. The tumor-associated antigen (TAA) CEA is overexpressed by a variety of cancer cell types, including those of the gastrointestinal tract, lung, and breast.
An agonist mouse monoclonal antibody directed against TRAIL death receptor type 5 (DR5) with potential antineoplastic activity. Anti-DR5 agonist monoclonal antibody TRA-8 binds DR5, which may induce apoptosis in DR5-expressing tumor cells. DR5 is a tumor cell surface ligand that crosslinks with death receptor type 4 (DR4) when bound by TRAIL [Tumor necrosis (TNF)-related apoptosis-inducing ligand], triggering apoptosis via a death receptor signaling pathway. The apoptotic activity of this antibody may not require DR4/DR5 crosslinking.
A glycoengineered monoclonal antibody directed against the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Anti-EGFR monoclonal antibody RO5083945 binds to the extracellular domain of EGFR, preventing the activation and subsequent dimerization of the receptor; the decrease in receptor activation and dimerization may result in an inhibition of downstream ERK and JNK signaling pathways and so inhibition of EGFR-dependent tumor cell proliferation and metastasis. EGFR, a member of the epidermal growth factor family of extracellular protein ligands, may be overexpressed on the cell surfaces of various solid tumor cell types.
An auristatin analogue immunoconjugate directed against Eph receptor A2 (EphA2)-positive cancer cells with potential antineoplastic activity. Anti-EphA2 monoclonal antibody-MMAF immunoconjugate MEDI-547 is generated by conjugating the fully human IgG1 anti-EphA2 monoclonal antibody (1C1) to the small-molecule microtubule inhibitor monomethyl auristatin phenylalanine (MMAF) via the stable linker maleimidocaproyl (mc) (1C1-mcMMAF). The monoclonal antibody moiety of this agent selectively binds to cells expressing the EphA2 receptor. After internalization and enzymatic cleavage of the immunoconjugate within the tumor cell cytosol, free MMAF binds to tubulin and inhibits its polymerization, which may result in G2/M phase arrest and tumor cell apoptosis. The cell-surface receptor EphA2, a member of the ephrin family of receptor tyrosine kinases (RTKs) involved in mammalian development, is overexpressed by a variety of different cancer cell types.
Autologous human peripheral blood lymphocytes (PBLs) transduced with a retroviral vector encoding an anti-Her-2 (epidermal growth factor receptor 2) chimeric T cell receptor (chimeric antigen receptor or CAR) gene with potential immunostimulatory and antineoplastic activities. Autologous PBLs from a patient with Her-2-positive cancer are pulsed with a retroviral vector that encodes the CAR gene specific for Her-2. After expansion in culture and reintroduction into the patient, anti-Her-2-CAR retroviral vector-transduced autologous peripheral blood lymphocytes, which express anti-Her-2-CAR on their cell surfaces, bind to Her-2 antigen on tumor cell surfaces. Subsequently, Her-2-expressing tumor cells may be lysed. Her-2 (ErbB-2), a receptor tyrosine kinase (RTK) overexpressed by a variety of cancer cell types, belongs to the EGFR superfamily and plays key roles in both tumor cell proliferation and tumor angiogenesis.
A fully human monoclonal antibody directed against programmed cell death-1 ligand 1 (PD-L1) with immune checkpoint inhibitory and potential antineoplastic activities. Anti-PD-L1 monoclonal antibody MDX-1105 binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1), which may enhance the T-cell-mediated immune response to neoplasms and reverse T-cell inactivation. PD-L1 is overexpressed by many human cancer cell types. PD-L1 binding to PD-1 on T-cells suppresses the immune system and results in immune evasion. PD-1, a transmembrane protein expressed on activated T-cells, is a negative regulator of the immune system that limits the expansion and survival of CD8+ T cells.
A humanized monoclonal antibody directed against placental growth factor (PLGF) with potential anti-angiogenic and antineoplastic acivities. Anti-PLGF monoclonal antibody TB-403 binds to PLGF, inhibiting the binding of PLGF to the vascular endothelial growth factor receptor, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. PLGF is a protein that belongs to the family of vascular endothelial growth factors (VEGFs).
A hydrochloride salt form of Aplaviroc, a C-C Chemokine Receptor Type 5 (CCR5) antagonist with activity against HIV-1. Aplaviroc inhibits HIV-1 entry via CCR5 coreceptor interaction.
The sodium salt form of aprosulate, a synthetic sulfated bis(lactobionic acid amide) derivative and heparin analogue with anticoagulant activity. Aprosulate is made up of two fully sulfated lactobionic acid moieties with a diamine spacer via two amide bonds. This agent inhibits thrombin by antagonizing heparin cofactor II (HCII) and thus blocking thrombin-induced platelet aggregation. It prolongs clotting time.
The anhydrous form of argatroban, a synthetic derivative of L-arginine with antithrombotic activity. Argatroban is a univalent and direct inhibitor of fibrin-bound thrombin. This agent reversibly binds to the thrombin active site, thereby preventing the thrombin-dependent reactions, which include the conversion of fibrinogen to fibrin; the activation of factors V, VIII and XI; the activation of protein C; and platelet aggregation. Argatroban is highly selective for thrombin and is able to inhibit the action of both free and clot-associated thrombin. As a result, stabilization of blood clots occurs and coagulation is inhibited.
A dietary supplement containing an extract powder derived from the root of the ashwagandha shrub with potential antineoplastic, antioxidant, immunostimulating and anti-angiogenic activities. Ashwagandha root powder extract contains numerous alkaloids, including withanine as the primary alkaloid, and steroidal lactone withanolides. The withanolides in this agent may suppress nuclear factor-kappaB activation and nuclear factor-kappaB-regulated gene expression, potentiating apoptosis and inhibiting tumor cell invasion. Cultivated in India and North America, ashwagandha (Withania somnifera Dunal or Indian ginseng) belongs to the Solanaceae (nightshade) family.
The dihydrochloride salt form of atiprimod, an orally bioavailable small molecule belonging to the azaspirane class of cationic amphiphilic agents with anti-inflammatory, antineoplastic, and anti-angiogenic activities. Atiprimod inhibits the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and AKT, blocking the signaling pathways of interleukin-6, vascular endothelial growth factor (VEGF) and downregulating the anti-apoptotic proteins Bcl-2, Bcl-XL, and Mcl-1. This results in the inhibition of cell proliferation, induction of cell cycle arrest, and apoptosis.
The dimaleate salt form of atiprimod, an orally bioavailable small molecule belonging to the azaspirane class of cationic amphiphilic agents with anti-inflammatory, antineoplastic, and antiangiogenic activities. Atiprimod inhibits the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and AKT, blocking the signaling pathways of interleukin-6 and vascular endothelial growth factor (VEGF) and downregulating the anti-apoptotic proteins Bcl-2, Bcl-XL, and Mcl-1. This results in the inhibition of cell proliferation, induction of cell cycle arrest, and apoptosis.
An anhydrous calcium salt form of atorvastin, a synthetic lipid-lowering agent.
The sodium salt of atorvastatin, a synthetic lipid-lowering agent. Atorvastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. This agent increases the number of LDL receptors on hepatic cell surfaces, enhancing the uptake and catabolism of LDL and reducing LDL production and the number of LDL particles, and lowers plasma cholesterol and lipoprotein levels. Like other statins, atorvastatin may also display direct antineoplastic activity, possibly by inhibiting farnesylation and geranylgeranylation of proteins such as small GTP-binding proteins, which may result in the arrest of cells in the G1 phase of the cell cycle. This agent may also sensitize tumor cells to cyctostatic drugs, possibly through the mTOR-dependent inhibition of Akt phosphorylation.
A cancer vaccine containing a live-attenuated strain of the bacterium Listeria monocytogenes (Lm) encoding human papillomavirus (HPV) type 16 E7 fused to a non-hemolytic listeriolysin O protein with potential immunostimulatory and antineoplastic activities. Upon vaccination, Listeria expresses the HPV 16 E7 antigen and activates the immune system to mount a cytotoxic T-lymphocyte (CTL) response against cancer cells expressing HPV 16 E7. This may result in tumor cell lysis. In addition, the Listeria vector itself may induce a potent immune response. HPV 16 E7, a cell surface glycoprotein and tumor associated antigen, is overexpressed in the majority of cervical cancer cells.
An orally bioavailable synthetic small molecule with potential antiangiogenic and antineoplastic activities. Aurora A kinase/tyrosine kinase inhibitor ENMD-2076 selectively binds to and inhibits non-specified tyrosine kinases and Aurora kinases (AKs). The inhibition of AKs may result in the inhibition of cell division and proliferation and may induce apoptosis in tumor cells that overexpress AKs; antiangiogenic activity is related to the inhibition of angiogenic tyrosine kinases. AKs are serine-threonine kinases that play an essential role in mitotic checkpoint control during mitosis and are important regulators of cell division and proliferation.
A ductal breast carcinoma which has spread from the original site of growth to another anatomic site.
A lobular breast carcinoma which has spread from the original site of growth to another anatomic site.
The microscopic appearance of a cell undergoing mitosis.
A monoclonal expansion of B-lymphocytes with or without the characteristic immunophenotype of chronic lymphocytic leukemia. It precedes virtually all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma.
A necrotic process affecting the tissues of the mouth.
A non-peptidomimetic, water soluble, cyclic urea that is a selective inhibitor of HIV-1 protease.
An orally bioavailable, small-molecule, multitargeted reversible tyrosine kinase inhibitor with potential antineoplastic activity. Multitargeted tyrosine kinase inhibitor JNJ-26483327 binds to and inhibits several members of the epidermal growth factor receptor (EGFR) family, including EGFR, HER2 and HER4; Src family kinases (Lyn, Yes, Fyn, Lck and Src); and vascular endothelial growth factor receptor type 3 (VEGFR3). By inhibiting several different signaling molecules that play crucial roles at various stages in tumorigenesis, this agent may inhibit tumor growth, invasion, migration and metastasis. In addition, JNJ-26483327 crosses the blood-brain barrier (BBB).
A plasmid DNA vaccine encoding the mouse tumor associated antigen tyrosinase-related protein-2 (TYRP2) with potential immunostimulating and antineoplastic activities. Upon administration, murine TYRP2 plasmid DNA vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing TYRP2; this vaccine may also induce an immune response against tyrosinase-related protein-1 (TYRP1). TYRP2 and TYRP1, melanosomal membrane glycoproteins upregulated in melanoma cells, are involved in melanin synthesis.
A cancer vaccine consisting of autologous ovarian cancer cell peptide antigens conjugated to the hapten 2,4-dinitrophenol (DNP) with potential immunostimulating and antineoplastic activities. Administration of autologous dinitrophenyl-modified ovarian cancer vaccine may induce a cytotoxic T-lymphocyte (CTL) response against ovarian cancer cells. DNP conjugation may enhance the immunogenicity of weakly immunogenic antigens.
An orally available phosphodiesterase type 5 (PDE5) inhibitor with vasodilatory activity. Avanafil selectively inhibits PDE5, thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa of the penis. The inhibition of cGMP degradation results in prolonged muscle relaxation, vasodilation, and blood engorgement of the corpus cavernosa, thereby prolonging penile erection.
A hydrochloride salt form of azacosterol, a sterol derivative of cholesterol that acts as a hypocholesteremic.
A dihydrochloride salt form of azalanstat, a synthetic imidazole that inhibits hepatic cholesterol biosynthesis by inhibiting the cytochrome P450 enzyme lanosterol 14alpha-demethylase.
A medoxomil prodrug of azilsartan, an angiotensin II receptor antagonist with antihypertensive activity. Upon hydrolysis, azilsartan selectively and competitively binds to the AT1 subtype angiotensin II receptor and blocks the binding of angiotensin II to the receptor, thus promoting vasodilatation and counteracting the effects of aldosterone. Converted from angiotensin I by angiotensin-converting enzyme (ACE), angiotensin II stimulates the adrenal cortex to synthesize and secrete aldosterone, decreasing sodium excretion and increasing potassium excretion, and acts as a vasoconstrictor in vascular smooth muscle.
A high grade B-cell lymphoma with blastoid features or features between diffuse large B-cell lymphoma and Burkitt lymphoma which lacks MYC, BCL2, and BCL6 rearrangements.
A whole cell melanoma cancer vaccine with potential immunostimulating and antineoplastic activities. B16alphaGal melanoma vaccine contains three types of human melanoma cell lines that are genetically engineered to express the alpha(1,3)-galactosyl (alphaGal) epitope on cell surfaces. The agent stimulates a hyperacute rejection of whole melanoma cancer cells expressing alphaGal epitopes, initiated by opsonization by anti-alphaGal antibodies and followed by antibody-dependent cell-mediated cytotoxicity (ADCC) and cell lysis. This results in the stimulation of a broader cytotoxic T-lymphocyte response (CTL) directed against tumor antigens on melanoma cells that do not express alphaGal. AlphaGal is not normally expressed in humans because alpha(1,3)-galactosyltransferase (Alpha-GT), the enzyme that catalyzes the synthesis of alphaGal epitopes on glycoproteins and glycolipids, is not naturally present in humans and other primates.
A B-cell acute leukemia characterized by the presence of lymphoblasts that carry a translocation between the TEL gene on chromosome 12 and the AML1 gene on chromosome 21, (p13.2;q22.1). It results in the production of the TEL-AML1 (ETV6-RUNX1) fusion protein. It is commonly seen in children and rarely in adults. It has a favorable clinical outcome.
A B-cell acute leukemia characterized by the presence of lymphoblasts that carry a translocation between the E2A gene on chromosome 19 and the PBX1 gene on chromosome 1. It occurs in children and less often in adults.
A rare B-cell acute leukemia characterized by the presence of lymphoblasts that carry a translocation between the IL3 gene on chromosome 5 and the IGH locus on chromosome 14, (q31.1;q32.3). It results in eosinophilia.
A B-cell acute leukemia characterized by the presence of lymphoblasts that carry a translocation between the KMT2A gene at 11q23.3 and another gene partner resulting in the production of a KMT2A related fusion protein. It is the most commonly seen leukemia in the pediatric population under the age of one year. The prognosis is unfavorable.
A precursor lymphoid neoplasm which is composed of B-lymphoblasts and carries a translocation between the KMT2A gene at 11q23.3 and another gene partner resulting in the production of a KMT2A related fusion protein.
The term refers to precursor lymphoid neoplasms which are composed of B-lymphoblasts and characterized by the absence of recurrent genetic abnormalities.
A precursor lymphoid neoplasm composed of B-lymphoblasts which contain more than 50 and usually less than 66 chromosomes. It has a favorable clinical outcome.
A precursor lymphoid neoplasm composed of B-lymphoblasts which contain less than 46 chromosomes. It has an unfavorable clinical outcome.
The term refers to precursor lymphoid neoplasms which are composed of B-lymphoblasts and characterized by the presence of recurrent genetic abnormalities.
A precursor lymphoid neoplasm which is composed of B-lymphoblasts and carries a translocation between the TEL gene on chromosome 12 and the AML1 gene on chromosome 21, (p13.2;q22.1). It results in the production of the TEL-AML1 (ETV6-RUNX1) fusion protein. It has a favorable clinical outcome.
A precursor lymphoid neoplasm which is composed of B-lymphoblasts and carries a translocation between the E2A gene on chromosome 19 and the PBX1 gene on chromosome 1.
A precursor lymphoid neoplasm which is composed of B-lymphoblasts and carries a translocation between the IL3 gene on chromosome 5 and the IGH locus on chromosome 14, (q31.1;q32.3). It results in eosinophilia.
A precursor lymphoid neoplasm which is composed of B-lymphoblasts and carries a translocation between the BCR gene on chromosome 22 and the ABL1 gene on chromosome 9. It results in the production of the p190 kd or p210 kd fusion protein. It has an unfavorable clinical outcome.
A humanized monoclonal antibody (IgG1) raised against amyloid beta peptides with Alzheimer disease treatment application. Bapineuzumab recognizes and binds the N-terminal amino acids 1-5 of the amyloid beta peptide, and may be used in a passive immunotherapy treatment.
A method to diagnosis hepatocellular carcinoma based on radiological findings, alfa-fetoprotein level and biopsy.
The anhydrous form of benfosformin, a phosphorylated biguanide derivative with antihyperglycamic activity. Benfosformin is associated with an increased risk of lactic acidosis.
A carotid body paraganglioma that is confined to the site of origin, without metastatic potential.
A benign tumor of the liver composed of hepatic stellate cells.
An aminosulfamoylbenzoic acid-based diuretic.
An orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Betrixaban is primarily excreted unchanged in the bile and has a half life of about 19 hours.
A dimeglumine formulation of bevirimat, a drug derived from a betulinic acid-like compound, first isolated from the Chinese herb Syzygium claviflorum, with activity against human immunodeficiency virus (HIV). Bevirimat acts by binding to the Gag capsid precursor protein and blocking its conversion to mature capsid protein by protease cleavage. It potently inhibits replication in both wild-type and drug-resistant (reverse transciptase or protease) HIV-1 isolates.
A transmucosal formulation consisting of a small, mucoadhesive, bioerodible polymer disc formulated with the citrate salt of fentanyl, a synthetic anilidopiperidine opioid with analgesic activity. Upon application, fentanyl buccal soluble film rapidly releases fentanyl which is quickly absorbed into the systemic circulation. Fentanyl selectively binds to and activates mu-opioid receptors in the central nervous system (CNS), thereby mimicking the effects of endogenous opiates.
A benign or malignant growth composed of proliferating neoplastic cells.
A non-nuceoside polymerase inhibitor with activity against hepatitis C virus (HCV). Nesbuvir binds to the palm site II pocket of HCV NS5B polymerase and inhibits viral genome replication.
An adverse event appears to have occurred, but there does not appear to have been a problem with a medical device or the way it was used.
A non-neoplastic disorder that affects the lips. Representative examples include inflammation and cleft lip.
Bleeding that is induced by gentle manipulation of the gingival tissue at the depth of the gingival sulcus.
The essential oil from the leaves of Peumus boldus. Boldo leaf oil is toxic and is used sparingly in preparations for gastrointestinal or genitourinary illnesses.
An orally bioavailable taxane with potential antineoplastic activity. Upon oral administration, milataxel and its major active metabolite M-10 bind to and stabilize tubulin, resulting in the inhibition of microtubule depolymerization and cell division, cell cycle arrest in the G2/M phase, and the inhibition of tumor cell proliferation. Unlike other taxane compounds, milataxel appears to be a poor substrate for the multidrug resistance (MDR) membrane-associated P-glycoprotein (P-gp) efflux pump and may be useful for treating multidrug-resistant tumors.
An oral tablet formulation containing zoledronic acid combined with a proprietary absorption enhancer for improved zoledronic acid gastrointestinal absorption with anti-bone-resorption activity. The third-generation bisphosphonate zoledronic acid binds to hydroxyapatite crystals in the bone matrix, slowing their dissolution and inhibiting the formation and aggregation of these crystals. This agent also inhibits farnesyl pyrophosphate synthase, an enzyme involved in terpenoid biosynthesis. Inhibition of this enzyme prevents the biosynthesis of isoprenoid lipids, donor substrates of farnesylation and geranylgeranylation during the post-translational modification of small GTPase signalling proteins, which are important in the process of osteoclast turnover. The proprietary absorption enhancer is a GRAS (generally-recognized-as-safe) food additive.
A peptide-based vaccine containing a pan HLA DR-binding epitope (PADRE) fused to a cytomegalovirus (CMV) peptide epitope, with potential anti-viral and immunomodulating activities. Upon administration, PADRE-CMV fusion peptide may stimulate a cytotoxic T-lymphocyte (CTL) response against CMV in the CMV-infected host. The synthetic peptide PADRE is a universal helper T cell epitope.
An injectable formulation of the polysaccharide beta 1,3/1,6 glucan derived from the cell wall of the yeast Saccharomyces cerevisiae with potential immunomodulating and antineoplastic activities. PGG beta-glucan binds to an alternate site on the neutrophil complement receptor 3 (CR3), priming the neurophil to become cytotoxic when binding to complement on tumor cells via CR3. This agent has been reported to selectively activate immune cells without inducing pro-inflammatory cytokines, potentially reducing potential side effects observed with the induction of broad innate immune repsonses. In addition, PGG beta-glucan may induce hematopoietic progenitor cell (HPC) mobilization.
An orally bioavailable, small molecule inhibitor of the delta isoform of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Idelalisib inhibits the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), preventing the activation of the PI3K signaling pathway and inhibiting tumor cell proliferation, motility, and survival. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in hematopoietic lineages. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells.
A phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor GSK1059615 inhibits PI3K in the PI3K/AKT kinase signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane and an increase in mitochondrial membrane permeability, followed by apoptosis. Bax is a member of the proapoptotic Bcl-2 family of proteins. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival.
A replication-defective (ICP4-deleted) herpes simplex virus type 1 (HSV-1) viral vector expressing the human preproenkephalin A (PPE) gene with potential antinociceptive activity. Upon intradermal administration, PPE-expressing replication-defective HSV-1 vector NP2 is transported by retrograde axonal transport to the dorsal root ganglion (DRG) and becomes dormant. In the DRG, the vector transduces sensory neurons with high efficiency, delivering the engineered PPE gene; transduced neurons then express the protein proenkephalin A, the precursor for Met- and Leu-enkephalin. After proteolytic cleavage from proenkephalin A in the DRG neuronal cytosol, transgene-mediated Met- and Leu-enkephalin bind to mu and gamma- opioid receptors, which may result in the inhibition of nociceptive neurotransmission.
A peptide-based cancer vaccine containing epitopes of T cell receptor gamma-chain alternate reading frame protein (TARP) and prostate-specific membrane antigen (PSMA) in combination with a Poly IC-LC immunoadjuvant, with potential antineoplastic activity. Upon administration, PSMA/TARP peptide vaccine may stimulate a host cytotoxic T-cell (CTL) response against TARP- and PSMA-expressing tumor cells, resulting in tumor cell cytotoxicity. The nuclear protein TARP and PSMA are commonly expressed in prostate cancer cells.
A vascular-acting photosensitizer consisting of a water-soluble, palladium-substituted bacteriochlorophyll derivative with potential antineoplastic activity. Upon administration, paldeliporfin is activated locally when the tumor bed is exposed to low-power laser light; reactive oxygen species (ROS) are formed upon activation and ROS-mediated necrosis may occur at the site of interaction between the photosensitizer, light and oxygen. Vascular-targeted photodynamic therapy (VTP) with padeliporfin may allow tumor-site specific cytotoxicity while sparing adjacent normal tissues.
A cancer vaccine consisting of a replication-defective recombinant canarypox virus [ALVAC(2)] encoding the cancer-testis antigen NY-ESO and the TRIad of COstimulatory Molecules (B7-1, ICAM-1 and LFA-3; also called TRICOM), with potential immunostimulatory and antineoplastic activities. Upon administration, ALVAC(2)/NY-ESO (M)/TRICOM vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against NY-ESO-expressing cancer cells, which may result in the inhibition of tumor cell proliferation. NY-ESO-1, a tumor associated antigen (TAA), is found in normal testis and on the surface of various tumor cells, including bladder, breast, hepatocellular, melanoma, and prostate tumor cells. TRICOM may enhance antigen presentation and activate cytotoxic T-cells. In addition, ALVAC(2) encodes the vaccinia virus (vv) E3L ad K3L genes, which may potentiate the translation of the NY-ESO and TRICOM genes.
A pyrazolo[1,5-a]pyrimidine with potential antineoplastic activity. Dinaciclib selectively inhibits cyclin dependent kinases CDK1, CDK2, CDK5, and CDK9; inhibition of CDK1 and CDK2 may result in cell cycle repression and tumor cell apoptosis.
A peptide-based cancer vaccine containing a mutated form of the HLA-A*0201-restricted cytomegaloviral epitope CMVpp65(495-503) with potential immunostimulatory and antitumor activities. Upon subcutaneous administration, CMVpp65-A*0201 peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against CMV-positive cells, resulting in cell lysis. HLA-A*0201 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*0201 may improve antigenic peptide immunogenicity. CMVpp65, a tegument protein of the herpes virus CMV, is the main viral antigen found in peripheral blood mononuclear cells (PBMCs) after viral infection and may activate cell-mediated immunity.
A group of connective tissue disorder caused by mutations in the COL1A1 gene mapped to chromosome 17q21. It includes the Ehlers-Danlos syndrome, osteogenesis imperfecta, and osteoporosis.
A nodal follicular lymphoma with favorable prognosis. It lacks BCL-2 rearrangement and 14;18 translocation. Nearly all cases are localized. It is usually seen in the pediatric population but similar lymphomas may occur in adults.
A nodal marginal zone lymphoma affecting the pediatric population, predominantly males. It presents with asymptomatic and localized (mainly head and neck) disease in the vast majority of cases. Morphologically there is often progressive transformation of the germinal centers. The prognosis is excellent.
An orally active, non-competitive, and selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, with anti-epileptic activity. Although the mechanism of action through which perampanel exerts its antiepileptic effect has not been fully elucidated, this agent antagonizes the AMPA subtype of the excitatory glutamate receptor found on postsynaptic neurons in the central nervous system (CNS). This antagonistic action prevents AMPA receptor activation by glutamate and results in the inhibition of neuronal excitation, repetitive neuronal firing, and the stabilization of hyper-excited neural membranes. Glutamate, the primary excitatory neurotransmitter in the CNS, plays an important role in various neurological disorders caused by neuronal hyperexcitation.
Philadelphia chromosome abnormality; t(9;22)(q34;q11) was found; bcr/abl gene rearrangement was found.
An unusual sensation in the area of pharynx. It may be the initial manifestation of seizures associated with temporal lobe epilepsy.
A plasmablastic lymphoma arising in the oral cavity, usually associated with HIV infection.
An aggressive mantle cell lymphoma characterized by the presence of pleomorphic neoplastic B-lymphocytes.
A dihydropteridinone Polo-like kinase 1 (Plk1) inhibitor with potential antineoplastic activity. Volasertib selectively inhibits Plk1, inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner.
An isotonic solution containing macrogol 3350 and electrolytes with laxative activity. Macrogol 3350-based oral osmotic laxative promotes the retention of water in the bowel, thereby increasing the water content of stool, which results in increased gastrointestinal motility and stool transit time and evacuation of colonic contents. Macrogol 3350 is also known as polyethylene glycol (PEG) 3350.
A multivalent cancer vaccine comprised of the five tumor-associated antigens (TAAs) globo H, GM2 ganglioside, Tn-MUC1, TF, and sTn conjugated with the immunoadjuvant keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. Upon administration, polyvalent antigen-KLH conjugate vaccine may induce production of IgG and IgM antibodies and antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells expressing these TAAs, resulting in tumor cell death and tumor growth inhibition. Globo H (globo H hexasaccharide 1); GM2 ganglioside; Tn-MUC1 (human tumor-associated epithelial mucin 1 carrying the tumor-specific glycan Tn); TF (Thompson-Friedreich); and sTn (sialyl-Tn) are overexpressed in a variety of cancer cells. KLH is a hapten carrier and serves as an immunostimulant to improve immune recognition of antigens.
A liquid extract preparation derived from pomegranate (Punica granatum) seeds with antioxidant, and potential antineoplastic and chemopreventive activities. Pomegranate liquid extract contains flavonoids which may promote differentiation and apoptosis in tumor cells by down-regulating vascular endothelial growth factor (VEGF) and stimulating migration inhibitory factor (MIF), thus inhibiting angiogenesis. Pomegranate liquid extract flavanoids also scavenge reactive oxygen species (ROS) and, in some cell types, may prevent ROS-mediated cell injury and death.
A follicular lymphoma arising from the intestine. The majority of cases occur in the small intestine, particularly the duodenum. Usually the patients have localized disease and a favorable clinical outcome.
A probiotic containing the bacterium Lactobacillus acidophilus with potential antimicrobial and immunomodulatory activities. As a dietary supplement, Lactobacillus acidophilus (L. acidophilus), a naturally-occurring bacteria, may improve digestion and help maintain adequate colonization of the gastrointestinal (GI) tract by modulating the composition of the normal microflora. Because it produces lactic acid and hydrogen peroxide and other substances during fermentation, this bacterium creates an acidic environment unfavorable to pathogens such as Candida albicans. In addition, during colonization of the GI tract, L. acidophilus may form a protective barrier, preventing attachment of pathogens. Dietary supplementation with this bacterium has been shown to enhance natural and acquired immunity in mice.
A dietary supplement consisting of a blend of 8 natural ingredients with potential antineoplastic and chemopreventive activities. This dietary supplement contains vitamin D3 (as cholecalciferol), vitamin E (as d-alpha tocopherol), selenium (as L-selenomethionine), epigallocatechin (green tea extract), saw palmetto (berry extract), lycopene, and the isoflavonoids daidzein and genistein. This combination preparation may decrease prostate cell growth and inhibit prostate carcinogenesis.
A derivative of the xanthine alkaloid theobromine with diuretic and vasodilating activity. Like other methylated xanthines, protheobromine causes diuresis, and acts as a stimulant and vasodilator.
A derivative of thiophene with antifungal activity.
An immunotoxin containing epitope of Pseudomonas exotoxin (PE) with immunotherapeutic property. PE, a peptide toxin of 613 amino acids, consists of 3 functional domains: an amino-terminal receptor-binding domain, a middle translocation domain, and a carboxyl-terminal ADP-ribosylation domain. The last 5 carboxyl-terminal amino acids, Arg-Glu-Asp-Leu-Lys, are critical for its cytotoxic action.
A dioxinoquinolone-based diuretic and chemically distinct from the thiazide diuretics. Quincarbate was never marketed.
The orally bioavailable solvate of the R-(-) enantiomer of gossypol and acetic acid with potential antineoplastic activity. As a BH3 mimetic, R-(-)-gossypol binds to the hydrophobic surface binding groove BH3 of the anti-apoptotic proteins Bcl-2 and Bcl-xL, blocking their heterodimerization with pro-apoptotic members of the Bcl-2 family of proteins such as Bad, Bid, and Bim; this may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Racemic gossypol is a polyphenolic compound isolated from cottonseed.
A calcium salt formulation of clofibrate, an aryloxyisobutyric acid derivate with antihyperlipidemic activity.
A synthetic analogue of camptothecin with potential antineoplastic and radio-sensitizing activities. Camptothecin analogue TLC388 selectively stabilizes topoisomerase I-DNA covalent complexes during S-phase, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. Topoisomerase I relaxes negative super-coiled DNA during replication and transcription. This agent has been chemically modified to enhance the potency and stability of camptothecin.
A grading of angina such that ordinary physical activity, such as walking or climbing stairs, does not cause angina. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation.
A grading of angina characterized by marked limitations of ordinary physical activity. Angina occurs on walking 1 to 2 blocks on the level and climbing 1 flight of stairs in normal conditions and at a normal pace.
The phenyl ester of carbenicillin, a broad-spectrum, semisynthetic penicillin derivative with antibacterial activity. Following absorption, carbenicillin phenyl sodium is rapidly hydrolyzed to the active carbenicillin, which binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, thereby preventing the cross-linkage of peptidoglycans, which are critical components of the bacterial cell wall. This leads to a weakening of the bacterial cell wall, eventually causing bacterial cell lysis.
A rare condition characterized by the development of a carcinoma in a pre-existing craniopharyngioma.
A synthetic co-substrate that activates the human endogenous enzyme NRH:quinone oxidoreductase 2 (NQO2) with potential chemoadjuvant activity. When caricotamide is administered simultaneously with the prodrug tretazicar, NQO2 converts tretazicar to the bifunctional alkylating agent dinitrobenzamide, which is capable of forming a high degree of DNA interstrand cross-links, resulting in the inhibition of DNA replication and the induction of apoptosis. NQO2 has been found to be over-expressed in cancers such as hepatocellular carcinoma (HCC), colorectal and ovarian cancers.
A combination therapy consisting of the prodrug tretazicar and the enzyme co-substrate caricotamide with potential antineoplastic activity. In the presence of separately and simultaneously administered caricotamide, tretazicar is converted to the short-lived cytotoxic DNA cross-linking agent dinitrobenzamide by NAD(P)H quinine oxidoreductase 2 (NQO2), resulting in the inhibition of DNA replication and the induction of apoptosis. NQO2 has been found to be elevated in certain cancers such as hepatocellular carcinoma (HCC).
A protein kinase inhibitor specific for the Raf and MEK mitogen-activated protein kinases (MAPKs) with potential anti-neoplastic activity. Raf/MEK dual kinase Inhibitor RO5126766 specifically inhibits the kinase activities of Raf and MEK, resulting in the inhibition of target gene transcription that promotes malignant transformation of cells. Both Raf and MEK are serine/threonine-specific kinases that respond to extracellular stimuli, such as mitogens, and are involved in the regulation of cellular processes, such as gene expression, mitosis, differentiation, and apoptosis.
A laboratory test result indicating the presence of recurrent genetic abnormalities in cells.
A recombinant protein that inactivates the ribosome with potential antineoplastic and immunomodulating activities. Ribosome-inactivating protein CY503 binds to the cell surface sialyltransferase CD75 and is internalized; intracellularly, CY503 cleaves an adenine-specific N-glycosidic bond on the 28S ribosomal subunit, which may result in tumor cell apoptosis. This agent has also been shown to activate natural killer (NK) cells, induce cytokine receptor expression, and stimulate the release of cytokines. CD75 is expressed on mature B-cells and subsets of T-cells and erythrocytes.
A small molecule vascular disrupting agent, with potential antimitotic and antineoplastic activities. Rosabulin binds to tubulin in a similar manner as colchicine and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells, ultimately leading to cell cycle arrest and blockage of cell division. By destroying proliferating vascular cells, blood flow to the tumor is reduced and eventually leads to a decrease in tumor cell proliferation.
A derivative of sphingosine, with potential antineoplastic activity. As a sphingosine derivative, cedefingol appears to inhibit protein kinase C (PKC), a kinase that plays an important role in tumorigenesis.
The sodium salt form of cefovecin, a semisynthetic, broad-spectrum, third-generation cephalosporin with antibacterial activity. Cefovecin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
The movement of one cell type into an area normally occupied by a different cell type.
The anhydrous form of cephalexin, a semisynthetic first-generation cephalosporin with antibacterial activity. Cephalexin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
A synthetic, water soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin, but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.
The hydrochoride salt form of chlorazanil, a triazine derivative and diuretic agent. Chlorazanil appears to prevent the absorption of sodium and chloride in the distal convoluted tubule.
A genetic syndrome caused by microdeletions in chromosome 17q21. The microdeletions encompass the MAPT and CRHR1 genes. It is characterized by mental retardation, hypotonia, distinctive facial features (long face, low-set ears, and pear-shaped nose), friendly behavior, and heart defects.
A genetic syndrome caused by terminal 22q13 microdeletions. It is characterized by developmental delay and delayed or absent speech.
An anhydrous form of cidofovir, a synthetic, acyclic monophosphate nucleotide analog of deoxycytidine with antiviral activity, mostly used against cytomegalovirus (CMV). After incorporation into the host cell, cidofovir is phosphorylated by pyruvate kinases to its active metabolite cidofovir diphosphate. Cidofovir diphosphate, bearing structural similarity to nucleotides, competes with deoxycytosine-5-triphosphate (dCTP) for viral DNA polymerase and gets incorporated into the growing viral DNA strands. As a result, it prevents further DNA polymerization and disrupts DNA replication of viruses.
An orally bioavailable, peptidomimetic, macrocyclic compound with activity against hepatitis C virus (HCV). Ciluprevir binds non-covalently to the active center of the HCV NS3-4A serine protease and prevents processing of viral proteins required for replication.
A double-stranded 15-mer oligonucleotide, corresponding closely to the signal transducer and activator of transcription 3 (STAT3) response element within the c-fos promoter, with potential antineoplastic activity. STAT3 decoy oligonucleotide binds specifically to activated STAT3 and blocks binding of STAT3 to DNA sequences on a variety of STAT3-responsive promoters, which results in the inhibition of STAT3-mediated transcription and, potentially, the inhibition of tumor cell proliferation. STAT3 is constitutively activated in a variety of cancers including squamous cell carcinoma of the head and neck, contributing to the loss of cell growth control and neoplastic transformation.
The sodium salt form of salcaprozate, an oral absorption promoter. Salcaprozate sodium may be used as a delivery agent to promote the oral absorption of certain macromolecules with poor bioavailability such as insulin and heparin.
The anhydrous form of saxagliptin, a potent, selective and competitive, cyanopyrrolidine-based, orally bioavailable inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Saxagliptin is metabolized into an, although less potent, active mono-hydroxy metabolite.
A test used to determine the amount of tears collected on a filter paper strip in 5 minutes.
A benzenesulfonamide-based agent with salidiuretic and antihypertensive effects.
A distinctive characteristic of the skin marked by the amount of sebum secreted by sebaceous glands.
A necrotic process involving the wall of the small intestine.
An orally bioavailable small molecule SMO (Smoothened) inhibitor with potential antineoplastic activity. SMO inhibitor BMS-833923 inhibits the sonic hedgehog (SHH) pathway protein SMO, which may result in a suppression of the SHH signaling pathway. SMO is a G-protein coupled receptor that lies just downstream of the SHH ligand cell surface receptor Patched-1 in the SHH pathway; in the absence of ligand Patched-1 inhibits SMO and ligand binding to Patched-1 results in increased levels of SMO. The SHH signaling pathway plays an important role in cellular growth, differentiation and repair; constitutive activation of this pathway is associated with uncontrolled cellular proliferation and has been observed in a variety of cancers.
A peroxisome proliferator-activated receptor (PPAR) pan agonist, with hypoglycemic activity. Sodelglitazar exerts higher binding affinity for the delta subtype as compared to gamma and alpha subtypes.
The sodium salt form of bensuldazic acid, a veterinary antifungal agent.
The sodium salt of glycididazole with potential radiosensitizing activity. Due to its low redox potential, glycididazole is selectively activated via bioreduction in hypoxic tumor cells and may sensitize hypoxic tumor cells to the cytotoxic effects of ionizing radiation.
An oral laxative formulation containing the stimulant cathartic sodium picosulfate as the primary active ingredient. Picosulfate acts on the enteric nerves in the intestinal wall to increase muscle contractions, thereby stimulating peristaltic action and promoting defecation. Other active ingredients are osmotic agents that increase stool water content.
An imidazolidinone-based aldosterone antagonist with potassium-sparing diuretic activity. Clazolimine antagonizes aldosterone at the mineralocorticoid receptor in the kidneys, thereby increasing sodium excretion and inhibiting potassium excretion.
A benzenedisulfonamide-based agent and carbonic anhydrase (CA) inhibitor with diuretic activity. Clofenamide inhibits CA, thereby preventing sodium, bicarbonate and thus water reabsorption in the proximal convoluted tubule resulting in diuresis.
A synthetic tumor-associated peptide (TUMAP)-based cancer vaccine directed against colorectal cancer with potential immunostimulatory and antineoplastic activities. Synthetic colorectal tumor-associated peptides vaccine IMA910 contains 13 different synthetic TUMAPs, each of which represents a tumor associated antigen (TAA) specific for colorectal cancer. Upon administration, this agent may elicit a cytotoxic T-lymphocyte (CTL) response against colorectal tumors expressing these TAAs, which may result in a reduction in colorectal tumor cell proliferation.
An extract derived from the mushroom Coriolus versicolor, containing polysaccharide K (PSK) and polysaccharide-peptide (PSP), with potential immunomodulating and antineoplastic activities. Coriolus versicolor extract has been shown to stimulate the production of lymphocytes and cytokines, such as interferons and interleukins, and may exhibit antioxidant activities. However, the precise mechanism of action(s) of this agent is unknown.
The acetate salt form of coticorelin, a synthetic peptide of neurohormone corticotropin-releasing factor (CRF), with potential antitumor and antiangiogenesis activities. Upon administration, corticorelin stimulates adrenocorticotropic hormone (ACTH) secretion from the anterior pituitary gland. In turn, ACTH stimulates cortisol production from the adrenal cortex and is regulated by a negative feedback mechanism. Corticorelin appears to inhibit swelling around brain tumors through reduction in vascular leakage and maintenance of endothelial cell integrity. This agent potentially suppresses vascularization and tumor cell growth through reduction of vascular endothelial growth factor (VEGF) that appears to be via activation of corticotrophin-releasing factor receptor 2 (CRFR2), a G protein-coupled receptor.
A small molecule that can increase progesterone receptor (PR) expression, with potential antineoplastic adjuvant activity. Upon intramuscular administration, cridanimod is able to induce the expression of PR in endometrial cancer. This could increase the sensitivity of endometrial cancer cells to progestin monotherapy. In combination with a progestin, cancer cells could be eradicated through increased PR-mediated signaling, leading to an inhibition of luteinizing hormone (LH) release from the pituitary gland, via a negative feedback mechanism, and, eventually, an inhibition of estrogen release from the ovaries. This leads to an inhibition of cellular growth in estrogen-dependent tumor cells. In addition, this agent is able to increase the production and release of interferon (IFN) alpha and beta. PR is often downregulated in endometrial cancer and makes it resistant to progestin-mediated hormone therapy.
An oral capsule containing curcumin, green tea extract, Polygonum cuspidatum extract, and soybean extract, with antioxidant and potential chemopreventive activities. The antioxidants in curcumin/green tea extract/Polygonum cuspidatum extract/soybean extract capsule bind to and neutralize free-radicals, which may prevent their genotoxic and carcinogenic effects.
A humanized monoclonal antibody directed against sphingosine 1-phosphate (S1P) with potential antiangiogenic and antineoplastic activities. Upon administration, sonepcizumab binds S1P, which may result in the inhibition of tumor angiogenesis. S1P is the extracellular ligand for the G protein-coupled lysophospholipid receptor EDG-1 (endothelial differentiation gene-1).
A small B-cell clonal lymphoproliferative disorder of the spleen that does not fall into any of the other categories of mature B-cell neoplasms.
An uncommon, indolent B-cell non-Hodgkin lymphoma composed of small B-lymphocytes involving the red pulp of the spleen, bone marrow, and peripheral blood. Patients often have massive splenomegaly. The peripheral blood examination reveals villous lymphocytes.
A rare genetic disorder often inherited in an autosomal manner characterized by limb malformations including syndactyly, median clefts of the hands and/or feet, and partial or complete absence of fingers or toes. It may be associated with other skeletal and extraskeletal abnormalities.
Replacement of the bronchial glandular epithelial cells by squamous cells.
Grade 0 is universally defined as absence of Adverse Events or within normal limits or values.
An topical ophthalmic formulation containing cyclosporine, an undecapeptide produced by the fungus Beauveria nivea, with immunosuppressant and anti-inflammatory activities. The exact therapeutic mechanism of action of cyclosporine is not known but may involve binding to the cellular protein cytophilin, resulting in inhibition of the enzyme calcineurin. This agent appears to specifically and reversibly inhibit immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited with T-helper cells as the primary target. Cyclosporine also inhibits lymphokine production and release.
A cystic lesion with a central keratin mass which is surrounded by squamous epithelium.
Cytotoxic T-lymphocytes (CTLs), specifically reactive to the cytomegalovirus (CMV) immediate early-1 (IE-1) protein, with immunomodulating activity. Adoptive immunotherapy with cytomegalovirus IE-1-specific cytotoxic T lymphocytes may help reconstitute CD8+ cytomegalovirus-specific CTL responses in CMV-infected immunocompromised hosts. IE-1 is one of the first CMV antigens expressed by CMV-infected cells, predominantly inducing a CD8+ CTL response.
A humanized IgG1 monoclonal antibody directed against the cell surface-associated protein Cripto and conjugated to the maytansinoid DM4 with potential antineoplastic activity. The monoclonal antibody moiety of DM4-conjugated anti-Cripto monoclonal antibody BIIB015 binds to the tumor associated antigen (TAA) Cripto; upon internalization, the DM4 moiety binds to tubulin and disrupts microtubule assembly/disassembly dynamics, resulting in inhibition of cell division and cell growth of Cripto-expressing tumor cells. Constitutively expressed during embryogenesis, Cripto belongs to the EGF-CFC family of growth factor-like molecules and plays a key role in signaling pathways of certain transforming growth factor-beta superfamily members; as a TAA, Cripto is overexpressed in carcinomas such as those of the breast, ovary, stomach, lung, and pancreas while its expression is absent in normal tissues.
An orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib binds to and inhibits the growth-promoting activities of these kinases. Apparently because of its less stringent binding affinity for the BCR-ABL kinase, dasatinib has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations. SRC-family protein-tyrosine kinases interact with variety of cell-surface receptors and participate in intracellular signal transduction pathways; tumorigenic forms can occur through altered regulation or expression of the endogenous protein and by way of virally-encoded kinase genes.
A recombinant fusion protein consisting of de-immunized and humanized anti-CD20 monoclonal antibody Leu16 fused to human cytokine interleukin-2 (IL2) with potential antineoplastic activity. The antibody moiety of DI-Leu16-IL2 immunocytokine binds to tumor cells expressing the CD20 antigen, which may result in an antibody-dependent cell-mediated cytotoxicity (ADCC) towards CD20-expressing tumor cells; the localized IL2 moiety of this fusion protein may stimulate natural killer (NK) and T-lymphocyte mediated immune responses, enhancing the ADCC response. De-immunization involves the modification of potential helper T cell epitopes that bind to MHC class II molecules; humanization involves combining recombinant murine variable (V) regions with human immunoglobulin light and heavy chain constant regions. CD20 antigen, a hydrophobic transmembrane protein located on normal pre-B and mature B lymphocytes, is overexpressed by various cancer cell types.
A soluble fusion protein composed of the extracellular domain of the activin receptor type IIA (ActRIIA) linked to the Fc portion of human IgG1 with anabolic bone activity. Sotatercept selectively binds to activin, inhibiting its binding to ActRIIA and ActRIIA signaling, resulting in the stimulation of osteoblast activity and the inhibition of osteoclast activity and so normal bone formation and increased bone mineral density and strength. The Fc moiety of this fusion protein binds to the salvage receptor FcRN, preventing its lysosomal degradation and so extending its half-life in the circulatory system.
A solitary fibrous tumor characterized by the presence of areas of abrupt transition to high grade sarcoma.
Abnormally late fusion of the bone growth plate.
A potent, selective, orally bioavailable, fluoropyrrolidine-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity.
A small molecular vascular disrupting agent (VDA), with potential antimitotic and antineoplastic activities. Denibulin selectively targets and reversibly binds to the colchicine-binding site on tubulin and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells, ultimately leading to cell cycle arrest, blockage of cell division and apoptosis. This causes inadequate blood flow to the tumor and eventually leads to a decrease in tumor cell proliferation.
An arsenic-containing agent formerly used in the treatment of syphilis.
An intravenous formulation containing E.coli-derived L-asparaginase II conjugated with succinimidyl carbonate monomethoxypolyethylene glycol (SC-PEG), with potential antineoplastic activity. L-asparaginase hydrolyzes L-asparagine to L-aspartic acid and ammonia, thereby depleting cells of asparagine; asparagine depletion blocks protein synthesis and tumor cell proliferation, especially in the G1 phase of the cell cycle and ultimately induces tumor cell death. Asparagine is critical to protein synthesis in acute lymphoblastic leukemia (ALL) cells which, unlike normal cells, cannot synthesize this amino acid due to the absence of the enzyme asparagine synthase. Pegylation decreases enzyme antigenicity and increases its half life. SC is used as a PEG linker to facilitate attachment to asparaginase and enhances the stability of the formulation.
An oral laxative containing sodium sulfate, potassium sulfate, magnesium sulfate and sucralose. Oral sulfate-based laxative BLI850 exhibits osmotic activity, attracting water into the intestinal tract from tissues and increasing the volume and the water content of the stool; gastrointestinal motility is stimulated, resulting in defecation. Sucralose, an artificial sweetener, may contribute to the laxative effect.
An ethacrynic derivative with diuretic activity.
A sulfanilamide derivative and carbonic anhydrase inhibitor with diuretic activity.
A furosemide derivative belonging to the class of loop diuretics.
Synpolydactyly (SPD), or syndactyly type II, is defined as a connection between the middle and ring fingers and fourth and fifth toes, variably associated with postaxial polydactyly in the same digits. Minor local anomalies and various metacarpal or metatarsal abnormalities may be present (summary by Merlob and Grunebaum, 1986). In some families with SPD, the foot anomalies are characterized by preaxial as well as postaxial polydactyly, and appear to be fully penetrant. The more severe features of classic SPD, involving 3/4 synpolydactyly in the hands and 4/5 synpolydactyly in the feet, also occur, but at reduced penetrance. This foot phenotype is not seen in patients with classic SPD due to HOXD13 polyalanine tract expansions (Goodman et al., 1998). Malik (2012) reviewed the syndactylies, noting that the extreme phenotypic heterogeneity observed in SPD families consists of approximately 18 clinical variants that can be 'lumped' into 3 categories: typical SPD features, minor variants, and unusual phenotypes. Genetic Heterogeneity of Synpolydactyly See also SPD2 (608180), caused by mutation in the fibulin-1 gene (FBLN1; 135820) on chromosome 22q13, and SPD3 (610234), which has been mapped to chromosome 14q11.2-q12.
An aggressive and life-threatening, EBV-positive T-cell lymphoma affecting children. It is more prevalent in Taiwan and Japan. Clinically, it presents with acute onset of fever and generalized malaise, followed by hepatosplenomegaly and liver failure. Morphologically it is characterized by the presence of infiltrating T-lymphocytes which are usually small and erythrophagocytosis. Most patients have a fulminant clinical course.
A preparation of transforming growth factor-beta (TGF-beta)-resistant cytotoxic T-lymphocytes (CTL) reactive to Epstein-Barr virus (EBV) latent membrane proteins 1 and 2 (LMP 1 and 2) with potential antineoplastic activity. T lymphocytes are transduced with a retroviral vector expressing the dominant-negative mutant type II TGF-beta receptor, which blocks signaling by all three TGF-beta isoforms. These TGF-beta-resistant T-lymphocytes are exposed ex-vivo to dendritic cells (DCs) transfected with a replication-deficient adenovirus encoding EBV LMP; subsequent exposure to LMP1- or LMP2-expressing lymphoblastoid cell lines is used to expand the CTL. Administered to patients with EBV-positive tumors, TGF-beta-resistant LMP-specific CTL target LMP-positive cells, which may result in a specific CTL response, followed by cell lysis and inhibition of tumor cell proliferation. Tumor-expressed TGF-beta inhibits T lymphocyte activation and expansion.
A poly-Toll-like receptor (TLR) agonist polyantigenic vaccine containing heat killed Mycobacterium indicus pranii (Mycobacterium w or Mw) with potential immunostimulating and antineoplastic activities. Upon administration, poly-TLR agonist polyantigenic vaccine activates a number of TLRs, which may result in macrophage and plasmacytoid dendritic cell (pDC) stimulation; secretion of interferon alpha; production of pro-inflammatory cytokines; upregulation of co-stimulatory molecules, enhanced T and B-cell stimulatory responses; T cell proliferation, and a Th1 immune response. TLRs are transmembrane receptors that recognize structurally conserved microbial molecules such as bacterial cell-surface lipopolysaccharides (LPS), lipoproteins, lipopeptides, lipoarabinomannan and flagellin, among others; immune responses stimulated by TLR activation may result in antineoplastic effects.
A diffuse large B-cell lymphoma arising in body cavities or narrow spaces of long standing chronic inflammation. The classic example is the pyothorax-associated lymphoma that arises in the pleural cavity of patients with a history of long standing pyothorax.
A term referring to a group of diffuse large B-cell lymphomas which are biologically heterogeneous. These lymphomas have a centroblastic, immunoblastic, or anaplastic morphology.
An injectable emulsion formulation containing the taxane docetaxel, a semisynthetic analogue of paclitaxel, with antineoplastic activity. Docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response. Docetaxel emulsion ANX-514 is formulated without polysorbate 80 or other detergents in order to reduce the incidence and severity of hypersensitivity reactions. In addition, the exclusion of polysorbate 80 in this formulation precludes foaming during the preparation process, thus facilitating preparation and administration.
A benzimidazole-quinolinone compound and receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Dovitinib binds to and inhibits the phosphorylation of type III-V RTKs, such as vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) that promote tumor cell proliferation and survival in certain cancer cells. In addition, this agent also inhibits other members of the RTK superfamily, including fibroblast growth factor receptor 1 and 3, FMS-like tyrosine kinase 3, stem cell factor receptor (c-KIT), and colony stimulating factor receptor 1. This may further lead to a reduction of cellular proliferation and angiogenesis, and an induction of tumor cell apoptosis.
An Epstein-Barr virus-associated mature T-cell lymphoproliferative group of disorders affecting children. It occurs with increased frequency in Asians and Native Americans. It includes the systemic EBV-positive T-cell lymphoma of childhood and the hydroa vacciniforme-like lymphoma.
An agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic activity. Edaglitazone also appears to lower triglyceride and free fatty acid levels.
The water soluble sodium salt of a small-molecule bis(thio-hydrazide amide) with oxidative stress induction, pro-apoptotic, and potential antineoplastic activities. Elesclomol induces oxidative stress, creating high levels of reactive oxygen species (ROS), such as hydrogen peroxide, in both cancer cells and normal cells. Because tumor cells have elevated levels of ROS compared to normal cells, the increase in oxidative stress beyond baseline levels elevates ROS beyond sustainable levels, exhausting tumor cell antioxidant capacity, which may result in the induction of the mitochondrial apoptosis pathway. Normal cells are spared because the increase in the level of oxidative stress induced by this agent is below the threshold at which apoptosis is induced.
An orally bioavailable, small-molecule, p38 mitogen-activated protein kinase (MAPK) inhibitor with potential immunomodulating, anti-inflammatory, and antineoplastic activities. Talmapimod specifically binds to and inhibits the phosphorylation of p38 MAPK, which may result in the induction of tumor cell apoptosis, the inhibition of tumor cell proliferation, and the inhibition of tumor angiogenesis. This agent may also enhance proteasome inhibitor-induced apoptosis. p38 MAPK is a serine/threonine protein kinase involved in a MAPK signaling cascade that controls cellular responses to various environmental stresses, cytokines, and endotoxins.
An ammonium salt of tallotrexin, an analogue of aminopterin with potential antineoplastic activity. As a folate antagonist, talotrexin binds to and inhibits the function of dihydrofolate reductase, resulting in the inhibition of folate metabolism, DNA synthesis, and cell division. Hydrosoluble, talotrexin is actively transported into cells by the reduced folate carrier (RFC) and, therefore, is unlikely to be associated with P-glycoprotein-mediated multidrug resistance.
A hydrochloride salt form of taribavirin, an orally available prodrug of ribavirin, a synthetic nucleoside analog of ribofuranose with activity against a wide range of viruses, especially the hepatitis C virus and influenza virus. Taribavirin is converted into ribavirin, which is incorporated into viral nucleic acid, thereby inhibiting viral RNA synthesis, inducing viral genome mutations, and inhibiting normal viral replication.
A trifluoroethyl derivative with antineoplastic agent.
A vaccine containing an inactivated epitope of tetanus toxin fused to a cytomegalovirus (CMV) peptide epitope, with potential anti-viral and immunomodulating activities. Upon administration, tetanus-CMV fusion peptide may stimulate a cytotoxic T-lymphocyte (CTL) response against CMV in the CMV-infected host. Tetanus toxin contains universal T cell helper epitopes.
Any structural or functional analogue that mimics the physiological actions of thyrotropin-releasing hormone (TRH). Although TRH analogues appear to have a minimal influence on the biosynthesis of TSH, they seem to exert various neuromodulating activities, such as central nervous system-stimulating, analeptic, analgesic, antidepressant, and neuroprotective effects.
A bicyclic heterocycle compound with activity against hepatitis B virus.
A topical formulation of a pentacyclic lupane-type triterpene derivative of betulin (isolated from the bark of Betula alba, the common white birch) with antiinflammatory, anti-HIV and antineoplastic activities. Betulinic acid induces apoptosis through induction of changes in mitochondrial membrane potential, production of reactive oxygen species, and opening of mitochondrial permeability transition pores, resulting in the release of mitochondrial factors involved in apoptosis, activation of caspases, and DNA fragmentation. Although originally thought to exhibit specific cytotoxicity against melanoma cells, this agent has been found to be cytotoxic against non-melanoma tumor cell types including neuroectodermal and brain tumor cells.
A topical cream containing the ester prodrug myristyl nicotinate (MN), a lipophilic nicotinic acid derivative with potential chemopreventive activity. Upon topical application, myristyl nicotinate penetrates into the epidermis where the agent is cleaved and is converted into nicotinic acid (niacin); nicotinic acid then diffuses into cells where it is converted to nicotinamide adenine dinucleotide (NAD). NAD may stimulate poly(ADP-ribose) polymerase-1 (PARP-1); enhance skin cell turnover and epidermal differentiation; and strengthen skin barrier function. NAD is a coenzyme that plays a crucial role in many redox reactions; PARP-1 is an enzyme that plays an important role in DNA repair.
A 9-aza-anthrapyrazole antineoplastic antibiotic. Topixantrone intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Compared to other DNA intercalators, this agent shows minimal cardiotoxicity.
The hydrochloride salt of a semisynthetic derivative of camptothecin mixed with sphingomyelin/cholesterol and sonicated to form small unilamellar vesicles containing topotecan, with potential antineoplastic activity. Topotecan hydrochloride liposomes mediates efficient drug delivery of topotecan into the cytosol from the endosome compartment. During the S phase of the cell cycle, topotecan selectively stabilizes topoisomerase I-DNA covalent complexes, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery.
A transforming growth factor (TGF)-beta2 specific phosphorothioate antisense oligodeoxynucleotide with the sequence 5'-CGGCATGTCTATTTTGTA-3', with potential antineoplastic activity. Trebedersen binds to TGF-beta2 mRNA causing inhibition of protein translation, thereby decreasing TGF-beta2 protein levels; decreasing intratumoral TGF-beta2 levels may result in the inhibition of tumor cell growth and migration, and tumor angiogenesis. TGF-beta2, a cytokine often over-expressed in various malignancies, may play an important role in promoting the growth, progression, and migration of tumor cells.
An anhydrous formulation of entecavir, a synthetic analog of 2-deoxyguanosine with antiviral activity against hepatitis B virus (HBV). Entecavir is activated in vivo to a 5-triphosphate metabolite. In turn, the triphosphate form competes with the natural substrate deoxyguanosine triphosphate (dGTP) for incorporation into viral DNA. The incorporation of the activated triphosphate metabolite of entecavir inhibits the reverse transcriptase (RT) viral RNA-dependent HBV DNA polymerase and, so, the replication of viral DNA and transcription.
A deoxyuridine analogue with antiviral activity against Herpes simplex and Varicella zoster viruses.
An epoxide and alkylating agent with antineoplastic activity. Epipropidone is not used clinically due to its unstable nature.
A trifluoroethylthio-containing benzothiadiazine sulfonamide derivative belonging to the class of the thiazide diuretics.
A second-generation epothilone with potential antineoplastic activity. Epothilone KOS-1584 binds to tubulin and induces microtubule polymerization and stabilizes microtubules against depolymerization, which may result in the inhibition of cell division, the induction of G2/M arrest, and apoptosis. Compared to first-generation epothilones, this agent exhibits greater safety and efficacy with an enhanced pharmaceutical profile, including enhanced water solubility and tumor penetration, and reduced CNS exposure. In addition, epothilone KOS-1584 is a poor substrate for the P-glycoprotein (P-gp) drug efflux pump.
A diffuse large B-cell lymphoma originally described in patients older than 50 years but it has been increasingly recognized in younger patients. Epstein-Barr virus is present in all cases. There is no known history of immunodeficiency or prior lymphoma.
An erbB receptor tyrosine kinase inhibitor with potential antineoplastic activity. erbB kinase inhibitor AZD8931 binds to and inhibits erbB tyrosine receptor kinases, which may result in the inhibition of cellular proliferation and angiogenesis in tumors expressing erbB. The erbB protein family, also called the epidermal growth factor receptor (EGFR) family, plays major roles in tumor cell proliferation and tumor vascularization.
An orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Eribaxaban is no longer on the market.
An orally bioavailable small molecule and ATP-competitive focal adhesion kinase (FAK) inhibitor with potential antineoplastic and antiangiogenic activities. FAK inhibitor PF-00562271 inhibits the tyrosine kinase FAK, and to a lesser extent, proline-rich tyrosine kinase (PYK2), which may inhibit tumor cell migration, proliferation, and survival. As FAK is a signal transducer for integrins, inhibition of FAK by this agent may prevent integrin-mediated activation of several downstream signals including ERK, JNK/MAPK and PI3K/Akt. FAK and PYK2, upregulated in many tumor cell types, are involved in tumor cell invasion, migration and proliferation.
A proprietary transferrin receptor-targeted nanoparticle preparation of a non-chemically modified small-interfering RNA (siRNA) directed against the M2 subunit of ribonucleotide reductase (RRM2) with potential antineoplastic activity. Upon administration, transferrin receptor-targeted anti-RRM2 siRNA CALAA-01 binds to transferrin receptors (TfRs), releasing anti-RRM2 siRNA after endocytosis; anti-RRM2 siRNA silences the expression of RRM2 via the RNAi pathway, impeding the assembly of the holoenzyme ribonucleotide reductase (RR) which catalyzes the production of deoxyribonucleotides. As a result, inhibition of cellular proliferation may occur in cells expressing TfR, a cell surface protein overexpressed on various cancer cell types.
A semi-synthetic derivative of the vinka alkaloid vinblastine with potential antineoplastic activity. Tubulin inhibitor ALB 109564(a) binds to tubulin monomers and inhibits microtubule formation, resulting in disruption of mitotic spindle assembly and arrest of tumor cells in the G2/M phase of the cell cycle.
An orally bioavailable small-molecule with tubulin-inhibiting, vascular-disrupting, and potential antineoplastic activities. Lexibulin inhibits tubulin polymerization in tumor blood vessel endothelial cells and tumor cells, blocking the formation of the mitotic spindle and leading to cell cycle arrest at the G2/M phase; this may result in disruption of the tumor vasculature and tumor blood flow, and tumor cell death.
A malignant ovarian epithelial tumor. It has been described in mice and rats and is characterized by marked pleomorphism, atypia, and an infiltrative growth pattern.
A benign ovarian epithelial tumor. It has been described in mice and rats and is rare in other animal species. Morphologically it is characterized by the presence of tubular structures and interstitial stroma.
A side effect of cancer treatment. It has been described in patients with chronic lymphocytic leukemia treated with lenalidomide, breast cancer patients during the initial phase of hormonal treatment, and in prostate cancer patients treated with luteinizing hormone-releasing hormone agonists. Symptoms include a sudden and painful increase in the tumor size, rash, low grade fever, bone pain, hypercalcemia, and an increase in the tumor markers levels.
A thiocarboxanilide non-nucleoside reverse transcriptase inhibitor. UC-781 is a potent inhibitor of reverse transcriptase-dependent pyrophosphorolysis, and purportedly restores the chain-terminating activity of zidovudine (AZT) against AZT-resistant virus.
An ultralow-molecular-weight heparin (ULMWH) (Mw: 2000-3000 daltons)consisting of a polydisperse mixture of oligomeric heparin fragments with potential anticoagulant activity. Ultralow-molecular-weight heparin AVE5026 binds to and activates antithrombin III (ATIII), which may result in the inhibition of activated factor Xa and, to a much lesser extent, factor IIa (thrombin) and so the inhibition of fibrin formation. Compared to low-molecular-weight heparins (LMWHs), AVE5026 exhibits an even higher ratio of anti-Factor Xa to anti-Factor IIa activity (>30:1). Compared to unfractionated heparins, the use of LMWHs is associated with lower incidences of major bleeding, osteoporosis and heparin-induced thrombocytopenia. Like LMWHs, this agent may inhibit tumor growth by regulating angiogenesis and apoptosis. AVE5026 is prepared by partial depolymerization of unfractionated porcine mucosal heparin.
A rare, mature T-Cell lymphoma arising from the skin.
An intrinsic narrowing of a lumen of the urinary tract.
Congenital or acquired narrowing of the lumen of the uterine cervix.
An oral formulation containing a small-molecule receptor tyrosine kinase inhibitor of both vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) with potential antineoplastic activity. TAK-593 selectively binds to and inhibits VEGFR and PDGFR, which may result in the inhibition of angiogenesis and tumor cell proliferation.
A highly tumor-selective vaccinia virus (vv) with an engineered double deletion (DD) of the thymidine kinase (tk) and vaccinia growth factor genes and additions of both a cytosine deaminase (CD) gene and a somatostatin receptor (SR) gene with potential oncolytic viral activity. The tk and vaccinia growth factor gene deletions in intratumorally administered vaccinia virus (vvDD-CDSR) help to restrict its replication and cytolytic activity to tumor cells with large nucleotide pools and tumor cells with activation of the EGFR-Ras pathway. Addition of the CD gene to the viral genome allows control of oncolytic viral infection through the administration of the prodrug 5-fluorocytosine (5-FC), converted by CD to the antimetabolite 5-fluorouracil (5-FU) in cells infected with this agent. Addition of the SR gene allows anatomical localization of vaccinia virus (vvDD-CDSR) through the use of octreotide scintigraphy.
A piperazine derivative, PHOSPHODIESTERASE 5 INHIBITOR and VASODILATOR AGENT that is used as a UROLOGICAL AGENT in the treatment of ERECTILE DYSFUNCTION.
A cancer vaccine consisting of a recombinant adenoviral vector encoding the tumor-associated antigen (TAA) human MUC-1 (hMUC-1) linked to the extracellular domain (ecd) of the co-stimulatory molecule CD40 ligand (CD40L) and an adenovirus signal sequence that encodes a secretory signal peptide (Ad-sig) with potential immunostimulating and antineoplastic activities. Due to the presence of the secretory signal peptide expressed by Ad-sig in the vaccine construct, transfected cells may secrete a fusion protein composed of hMUC-1 and the CD40L ecd. The CD40L moiety part of the fusion protein binds to CD40 receptors on dendritic cells (DCs). Subsequently, DCs may be activated and migrate, T-cells may expand, and a cytotoxic T lymphocyte (CTL) response against tumor cells that overexpress hMUC-1 may follow. MUC-1 is a hypoglycosylated TAA overexpressed by epithelial cancer cells.
A recombinant type 5 adenovirus (Ad5), encoding the gene for the human sodium-iodide symporter (NIS) linked to the cytomegalovirus (CMV) promoter, with potential gene transfection activity. Upon intratumoral injection, Ad5-CMV-NIS is taken up by tumor cells, resulting in the cellular expression of NIS. Subsequently, orally administered iodine 131 is taken up by NIS-expressing tumor cells, which may result in the selective accumulation of a cytotoxic dose of beta and gamma radiation in non-thyroidal tumor cells, sparing adjacent normal tissue. NIS, an intrinsic membrane glycoprotein, is an ion pump that actively transports iodide into cells which concentrate iodine; in addition to thyroid epithelial cells, it is found in non-thyroidal tissues including the salivary glands, the gastric mucosa, and lactating mammary glands.
Skin which is extremely pale white and it always burns when exposed to the sun. It is seen in people with blond or red hair and blue or hazel eyes.
Skin which is white and it usually burns easily when exposed to the sun. It is usually seen in people with blond or red hair and blue or hazel eyes.
Skin which is darker white and it sometimes burns when exposed to the sun. This type of skin can be seen in people with any hair or eye color.
Skin which is light brown and it rarely burns when exposed to the sun. It is usually seen in people of Mediterranean origin.
Skin which is brown and it burns very rarely when exposed to the sun. It is usually seen in people of Middle Eastern origin.
Skin which is dark brown or black and it never burns when exposed to the sun.
A classification system used by dermatologists to determine a person's risk for sunburn. The classification is based on the skin complexion and the degree of tolerance to sun exposure and it relates to the amount of melanin pigment in the skin. It was developed by Dr. Thomas Fitzpatrick in 1975 to determine patient's skin reaction to laser and light therapy treatments. According to this system, there are six skin varieties classified from I to VI.
An oral hyperosmotic saline laxative containing sodium biphosphate and sodium phosphate. Sodium phosphate/sodium biphosphate oral laxative promotes retention of water in the bowel, thereby increasing stool water content and volume, which results in increased gastrointestinal motility and stool transit time and evacuation of colonic contents.
A variant of peripheral T-cell lymphoma, not otherwise specified. It is characterized by the formation of nodular lymphocytic aggregates of atypical clear cells, either within the lymphoid follicles in a background of progressive transformation of germinal centers, or in the perifollicular areas.
A galactose mustard compound, an alkylating agent, with antineoplastic activity.
An anhydrous form of vidarabine, a nucleoside analog with activity against herpes simplex virus and varicella zoster virus. Vidarabine is converted to a monophosphate by viral thymidine kinase and is further modified to a triphosphate form by host enzymes. Vidarabine triphosphate directly inhibits DNA polymerase and also acts as a chain terminator in DNA replication.
The ditartrate salt of vinflunine, a bi-fluorinated derivative of the semisynthetic vinca alkaloid vinorelbine with potential antimitotic and antineoplastic activities. Vinflunine binds to tubulin and inhibits tubulin assembly and disrupts microtubule assembly dynamics. This results in cell cycle arrest in mitosis and an induction of apoptosis.
An immunotherapeutic consisting of the recombinant fusion protein WT1-A10 combined with the adjuvant ASO1B with potential immunostimulating and antineoplastic activities. Upon administration, WT1-A10/AS01B immunotherapeutic GSK2130579AWT1 may induce a WT1-specific cytotoxic T-lymphocyte (CTL) response against WT1-expressing tumor cells, resulting in cell lysis and the inhibition of cellular proliferation. The tumor-associated antigen WT1 (Wilms tumor protein-1) is overexpressed in most types of leukemia and in a variety of solid cancers. WT1-A10 is a 292 amino acid recombinant fusion protein consisting of a 12-mer truncated tat sequence (leader sequence) and amino acids number 2-281 of the WT1 sequence; ASO1B consists of a combination of the adjuvants monophosporyl lipd A (MPL) and Q21.
A rare autosomal dominant syndrome caused by mutations in the MITF and SNAI2 genes. It has all of the features of Waardenburg syndrome Type 1 except dystopia canthorum.
A heat-stable extract of white button mushrooms (Agaricus bisporus) with potential chemopreventive and immunomodulating activities. Phytochemicals, such as polysaccharides and especially beta-D-glucans found in the white button mushroom extract, bind to and inhibit the activity of aromatase, an enzyme responsible for the conversion of androgens to estrogens and which is often upregulated in breast cancer cells. The consequent decrease in estrogen production may result in the suppression of estrogen-dependent cellular proliferation. In addition, this extract may promote dendritic cell (DC) maturation, increase interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) production, and may enhance natural killer (NK) cell activity, thus amplifying both innate and T cell-mediated immune responses against cancer cells.
A radioimmunoconjugate comprised of a chimeric monoclonal antibody against human carcinoembryonic antigen (CEA) conjugated with the radioisotope yttrium 90 (Y-90) via the chelator tetra-azacyclododecanetetra-acetic acid (DOTA) with potential antineoplastic activity. The antibody moiety of yttrium Y90 DOTA anti-CEA monoclonal antibody cT84.66 binds to cells expressing the CEA antigen. Upon cellular internalization, this agent selectively delivers a cytotoxic dose of beta radiation. CEA, a tumor associated antigen, is overexpressed in many cancer types, including gastrointestinal, breast, non-small cell lung, and thyroid cancers.
A radioimmunoconjugate comprised of the recombinant chimeric monoclonal antibody cetuximab labeled with the radioisotope zirconium Zr 89 (Zr 89) with radioisotopic activity and potential imaging use. The antibody moiety of zirconium Zr 89 cetuximab binds to the extracellular domain of the epidermal growth factor receptor (EGFR). Upon binding, the radioisotope moiety may be detected using positron emission tomography (PET), allowing the imaging and quantification of EGFR-expressing tumor cells. EGFR is a tyrosine kinase that may be overexpressed on the cell surfaces of various tumor cell types.
The trisodium salt form of zoledronate, a synthetic imidazole, third generation bisphosphonate analog of pyrophosphate with antiresorptive activity. Zoledronate binds to hydroxyapatite crystals in the bone matrix and inhibits farnesyl pyrophosphate (diphosphate) synthase, thereby preventing protein prenylation within the mevalonate pathway. This leads to the loss of downstream metabolites essential for osteoclast function, leading to the induction of apoptosis and eventually, osteoclast-cell death. By preventing osteoclast-mediated bone resorption, zoledronate decreases bone turnover and stabilizes the bone matrix.
Anhydrous form of a synthetic imidazole third generation bisphosphonate analog of pyrophosphate with antiresorptive activity. Zoledronate binds to hydroxyapatite crystals in the bone matrix and inhibits farnesyl pyrophosphate (diphosphate) synthase, thereby preventing protein prenylation within the mevalonate pathway. This leads to the loss of downstream metabolites essential for osteoclast function, leading to the induction of apoptosis and eventually, osteoclast-cell death. By preventing osteoclast-mediated bone resorption, zoledronate decreases bone turnover and stabilizes the bone matrix.
A difluorocyclopropyl quinoline. Zosuquidar binds with high affinity to P-glycoprotein and inhibits P-glycoprotein-mediated multidrug resistance (MDR). P-glycoprotein, encoded by the MDR-1 gene, is a member of the ATP-binding cassette superfamily of transmembrane transporters and prevents the intracellular accumulation of many natural product-derived cytotoxic agents.
An iodine 123-radiolabeled small molecule that exhibits high affinity for prostate-specific membrane antigen (PSMA) with potential use in molecular imaging. 123-I-MIP-1095, a radiolabeled glutamate-urea-lysine analogue, selectively binds PSMA, which allows imaging of PSMA-expressing prostate cancer cells with gamma scintigraph. PSMA is a transmembrane glycoprotein highly expressed by malignant prostate epithelial cells and vascular endothelial cells of various solid tumors.
An equimolar gas mixture of oxygen (O2) and nitrous oxide (N2O) with potential analgesic activity. Upon inhalation, 50% oxygen/50% nitrous oxide premix produces rapidly reversible analgesia. The exact mechanism through which nitrous oxide exerts its analgesic effect has yet to be fully elucidated, but it appears to be associated with the neuronal release of endogenous opioid peptides.
The fluorine-18 (18F)-radiolabeled pyrimidine analog 5-fluorouracil (5-FU) with positron-emitting activity. Upon administration, 5-[18F]fluorouracil distribution in tumor tissue may be measured with positron emission tomography (PET). The degree of 5-[18F]fluorouracil uptake in tumor tissue may help to predict the response to 5-fluorouracil-based chemotherapy or to determine the response to other therapeutic agents used to treat 5-FU-sensitive tumors.
An ointment formulation containing the sulfate salt of 8-hydroxyquinoline in a petrolatum and lanolin base with skin-protecting activity. Upon topical application, 8-hydroxyquinoline sulfate exhibits antiseptic activity while lanolin moisturizes and softens skin.
A pyrimidinediamine derivative and dihydrofolate reductase inhibitor related to trimethoprim, with bactericide and diuretic activities. Aditeren has never been marketed.
Waardenburg syndrome type 2 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; and the absence of 'dystopia canthorum,' the lateral displacement of the inner canthus of each eye, which is seen in some other forms of WS (review by Read and Newton, 1997). Individuals with WS type 2E, which is caused by mutation in the SOX10 gene (602229), may have neurologic abnormalities, including mental impairment, myelination defects, and ataxia. Waardenburg syndrome type 2 is genetically heterogeneous (see WS2A; 193510). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS3 (148820), and WS4 (277580).
Idiopathic scoliosis is a structurally fixed lateral curvature of the spine with a rotatory component. There is at least a 10 degree curvature as demonstrated by upright spine roentgenograms by the Cobb method (Weinstein, 1994). Scoliosis may occur secondary to other hereditary disorders including Marfan syndrome (154700), dysautonomia (223900), neurofibromatosis (see 162200), Friedreich ataxia (see 229300), and muscular dystrophies. Genetic Heterogeneity of Susceptibility to Isolated Scoliosis Loci for isolated scoliosis have been mapped to chromosome 19 (IS1), chromosome 17 (IS2; 607354), chromosome 8 (IS3; 608765), chromosome 9q31-q34 (IS4; 612238), and chromosome 17q25-qter (IS5; 612239).
The succinate salt of vatalanib, an anilinophthalazine derivative, with antineoplastic activity. Vatalanib binds to and inhibits the protein kinase domain of vascular endothelial growth factor receptors 1 and 2; both receptor tyrosine kinases are involved in angiogenesis. This agent also binds to and inhibits related receptor tyrosine kinases, including platelet-derived growth factor (PDGF) receptor, c-Kit, and c-Fms.
The phenylhydrazone 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone formulated as a topical agent with immunomodulating and potential antineoplastic activities. Applied topically as a gel, sivifene may stimulate a local immune response against human papillomavirus (HPV)-induced cervical intraepithelial neoplasia (CIN).
Dermatosparaxis (meaning 'tearing of skin') is an autosomal recessive disorder of connective tissue resulting from deficiency of procollagen peptidase, an enzyme that aids in the processing of type I procollagen. The disorder and the responsible biochemical defect was first observed in cattle (Lapiere et al., 1971). Lapiere and Nusgens (1993) reviewed the discovery of dermatosparaxis in cattle, the elucidation of the disorder, its occurrence in other animals, and the delayed recognition of the disorder in the human.
The tricosasodium salt of a synthetic 24-mer oligonucleotide containing 3 CpG motifs with potential antineoplastic and immunostimulatory activity. Agatolimod selectively targets Toll-like receptor 9 (TLR9), thereby activating dendritic and B cells and stimulating cytotoxic T cell and antibody responses against tumor cells bearing tumor antigens.
The orally bioavailable lactate salt of a benzimidazole-quinolinone compound with potential antineoplastic activity. Dovitinib strongly binds to fibroblast growth factor receptor 3 (FGFR3) and inhibits its phosphorylation, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell death. In addition, this agent may inhibit other members of the RTK superfamily, including the vascular endothelial growth factor receptor; fibroblast growth factor receptor 1; platelet-derived growth factor receptor type 3; FMS-like tyrosine kinase 3; stem cell factor receptor (c-KIT); and colony-stimulating factor receptor 1; this may result in an additional reduction in cellular proliferation and angiogenesis, and the induction of tumor cell apoptosis. The activation of FGFR3 is associated with cell proliferation and survival in certain cancer cell types.
Omenn syndrome is an inherited disorder of the immune system (immunodeficiency). Omenn syndrome is one of several forms of severe combined immunodeficiency (SCID), a group of disorders that cause individuals to have virtually no immune protection from bacteria, viruses, and fungi. Individuals with SCID are prone to repeated and persistent infections that can be very serious or life-threatening. Infants with Omenn syndrome typically experience pneumonia and chronic diarrhea. Often the organisms that cause infection in people with this disorder are described as opportunistic because they ordinarily do not cause illness in healthy people.In addition to immunodeficiency, children with Omenn syndrome develop autoimmunity, in which the immune system attacks the body's own tissues and organs. This abnormal immune reaction can cause very red skin (erythroderma), hair loss (alopecia), and an enlarged liver and spleen (hepatosplenomegaly). In addition, affected individuals have enlargement of tissues that produce infection-fighting white blood cells called lymphocytes. These include the thymus, which is a gland located behind the breastbone, and lymph nodes, which are found throughout the body.If not treated in a way that restores immune function, children with Omenn syndrome usually survive only until age 1 or 2.
The hydrochloride salt of a small-molecule inhibitor of heat shock protein 90 (HSP90) with antiproliferative and antineoplastic activities. Retaspimycin binds to and inhibits the cytosolic chaperone functions of HSP90, which maintains the stability and functional shape of many oncogenic signaling proteins and may be overexpressed or overactive in tumor cells. Retaspimycin-mediated inhibition of HSP90 promotes the proteasomal degradation of oncogenic signaling proteins in susceptible tumor cell populations, which may result in the induction of apoptosis.
A liposomal small-molecule glutathione analog inhibitor of glutathione S-transferase (GST) P1-1 with hematopoiesis-stimulating activity. After intracellular de-esterification, the active form of TLK199 (TLK117) binds to and inhibits GST P1-1, thereby restoring Jun kinase and MAPK pathway activities and promoting MAPK-mediated cellular proliferation and differentiation pathways. This agent promotes the proliferation and maturation of hematopoietic precursor cells, granulocytes, monocytes, erythrocytes and platelets.
A humanized, immunoglobulin G1 monoclonal antibody with potential antitumor activity. Farletuzumab specifically targets at glycoprotein 3 (GP-3), a cell surface antigen that is overexpressed on many epithelial-derived cancer cells. Upon binding to the GP-3 antigen, farletuzumab triggers a host immune response against GP-3 expressing cells resulting in cell lysis.
A small-molecule 3-aminopyrazole derivative with potential antineoplastic activity. Danusertib binds to and inhibits the Aurora kinases, which may result in cell growth arrest and apoptosis in tumor cells in which Aurora kinases are overexpressed. This agent may preferentially bind to and inhibit Aurora B kinase. Aurora kinases, a family of serine-threonine kinases, are important regulators of cellular proliferation and division.
A pyrrolotriazine-based compound and an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antineoplastic activity. BMS-540215 specifically targets and binds strongly to human VEGFR-2, a tyrosine kinase receptor and pro-angiogenic growth factor expressed almost exclusively on vascular endothelial cells. Blockade of VEGFR-2 by this agent may lead to an inhibition of VEGF-stimulated endothelial cell migration and proliferation, thereby inhibiting tumor angiogenesis.
Chromium ion requiring three electrons to return to its elemental state.
An infectious process affecting the anal area and the rectum.
A disorder characterized by an abnormal communication between a salivary gland and another organ or anatomic site.
An anomalous configuration of blood vessels that shunts arterial blood directly into veins without passing through the capillaries and that is located in the duodenum.
The technique used to administer the exposure assessment.
Malignant neoplasms that either originate from the bone marrow (e.g. myeloid leukemias) or involve the bone marrow as secondary-metastatic tumors (e.g. metastatic carcinomas to the bone marrow). --2003
An orally bioavailable retinoid acid receptor alpha (RARalpha) agonist and vitamin A derivative, with potential antineoplastic activity. Upon administration, RARalpha agonist IRX5183 binds to and activates RARalpha, which promotes RARalpha-mediated signaling. This results in the transcription of RARalpha-responsive genes, which are responsible for cellular differentiation and proliferation. This results in the induction of cellular differentiation and apoptosis, and leads to the inhibition of cellular proliferation and tumorigenesis. RARalpha is a nuclear receptor and a member of the steroid receptor superfamily; reduced RARalpha signaling is correlated with cancer development in a variety of cancer cell types.
A small molecule inhibitor of Nedd8 activating enzyme (NAE) with potential antineoplastic activity. Pevonedistat binds to and inhibits NAE, which may result in the inhibition of tumor cell proliferation and survival. NAE activates Nedd8 (Neural precursor cell expressed, developmentally down-regulated 8), an ubiquitin-like (UBL) protein that modifies cellular targets in a pathway that is parallel to but distinct from the ubiquitin-proteasome pathway (UPP). Functioning in diverse regulatory activities, proteins conjugated to UBLs like Nedd8 typically are not targeted for proteasomal degradation.
A DNA vaccine consisting of plasmids encoding the E6 and E7 genes of human papilloma virus (HPV) subtypes 16 and 18, respectively, with potential immunostimulating and antineoplastic activities. Administered via intramuscular electroporation, HPV DNA plasmids therapeutic vaccine VGX-3100 expresses E6 and E7 proteins, which may elicit a cytotoxic T-lymphocyte (CTL) response against cervical cancer cells expressing E6 and E7 proteins, resulting in tumor cell lysis. HPV type 16 and HPV type 18 are the most common HPV types involved in cervical carcinogenesis.
A soluble fusion protein consisting of the extracellular domain of human fibroblast growth factor receptor 1 (FGFR1) fused to the Fc portion of human immunoglobulin G1 (IgG1) with potential antineoplastic and anti-angiogenic activities. FGFR1 receptor antagonist FP-1039 prevents FGFR ligands, such as FGF1, FGF2, FGF4, from binding to their cognate receptors, thereby inhibiting the activation of the related FGFR tyrosine kinases. Inhibition of FGFR1 by this agent may retard tumor cell proliferation and induce tumor cell death. FP-1039 may also inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis. FGFR1 is a receptor tyrosine kinase upregulated in certain tumor cells and involved in tumor cellular proliferation, differentiation, angiogenesis, and survival; most ligands that bind to FGFR1 also bind to the related receptors FGFR3 and FGFR4.
A glycoengineered, fully human IgG1 monoclonal antibody directed against the extracellular domain of the human CD70 molecule with potential antineoplastic activity. Anti-CD70 fully human monoclonal antibody MDX-1411 selectivity binds to the extracellular domain of CD70, which may induce an antibody-dependent cellular cytotoxicity (ADCC) response against CD70-expressing tumor cells. CD70, the ligand for the costimulatory receptor CD27 and a member of the tumor necrosis factor (TNF) family, is found on renal cell carcinoma (RCC) cells among other cancer cell types.
A human monoclonal antibody directed against the human inhibitory killer IgG-like receptor (KIR) with potential immunostimulating and antineoplastic activities. Anti-KIR monoclonal antibody IPH 2101 binds to the KIR receptor expressed on human natural killer (NK) cells, which may prevent KIR-mediated inhibition of NK cells and permit NK cell-mediated anti-tumor cytotoxicity. KIRs are surface glycoproteins that bind to major histocompatibility complex (MHC)/human leukocyte antigen (HLA) class I subtypes on target cells; binding of KIRs inhibits NK cell-mediated cytotoxicity.
An orally bioavailable, second-generation hydroxamic acid-based inhibitor of histone deacetylase (HDAC), with potential antineoplastic activity. HDAC inhibitor VRx-3996 targets and inhibits HDAC, resulting in an accumulation of highly acetylated histones, the induction of chromatin remodeling, and the selective transcription of tumor suppressor genes; these events result in the inhibition of tumor cell division and the induction of tumor cell apoptosis. This agent may upregulate HSP70 and downregulate anti-apoptotic Bcl-2 proteins more substantially than some first-generation HDAC inhibitors. HDACs, upregulated in many tumor cell types, are a family of metalloenzymes responsible for the deacetylation of chromatin histone proteins.
An orally bioavailable mammalian target of rapamycin (mTOR) kinase inhibitor with potential antineoplastic activity. mTOR kinase inhibitor OSI-027 binds to and inhibits both the raptor-mTOR (TOR complex 1 or TORC1) and the rictor-mTOR (TOR complex 2 or TORC2) complexes of mTOR, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR is a serine/threonine kinase that is upregulated in some tumors and plays an important role downstream in the PI3K/Akt/mTOR signaling pathway.
An orally bioavailabe, small-molecule tyrosine kinase inhibitor with potential antineoplastic activity. MET tyrosine kinase inhibitor PF-04217903 selectively binds to and inhibits c-Met, disrupting the c-Met signaling pathway, which may result in the inhibition of tumor cell growth, migration and invasion of tumor cells, and the induction of death in tumor cells expressing c-Met. The receptor tyrosine kinase c-Met, also known as hepatocyte growth factor (HGF) receptor, is overexpressed or mutated in many tumor cell types, playing an important role in tumor cell proliferation, survival, invasion, and metastasis and angiogenesis.
An iodine 123-radiolabeled small molecule that exhibits high affinity for prostate-specific membrane antigen (PSMA) with potential use in molecular imaging. Iofolastat I123, a radiolabeled glutamate-urea-lysine analogue, selectively binds PSMA, which allows imaging of PSMA-expressing prostate cancer cells with gamma scintigraph. PSMA is a transmembrane glycoprotein highly expressed by malignant prostate epithelial cells and vascular endothelial cells of various solid tumors.
An immunoconjugate consisting of an anti-integrin monoclonal antibody covalently attached to the maytansinoid DM4, a derivative of the cytotoxic agent maytansine (DM1), with potential antineoplastic activity. Integrin-targeted immunoconjugate IMGN388 binds to tumor cell surface integrins; upon internalization, the DM4 moiety is released from the immunoconjugate, binding to tubulin and disrupting microtubule assembly/disassembly dynamics, which may result in inhibition of cell division and cell growth of integrin-expressing tumor cells. Integrins, a class of transmembrane cell surface receptors, link the extracellular matrix (ECM) to intracellular signaling pathways that control cell proliferation and differentiation.
A small-molecule inhibitor of heat shock protein (Hsp) 90 with potential antineoplastic activity. Hsp90 inhibitor BIIB028 blocks the binding of oncogenic client proteins to Hsp90, which may result in the proteasomal degradation of these proteins and so the inhibition of tumor cell proliferation. Hsp90 is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as Her2/Erbb2, Akt, Raf1, Bcr-Abl, and mutated p53, in addition to other molecules involved in cell cycle regulation and immune responses.
A synthetic, fungal metabolite analogue inhibitor of mitogen-activated protein kinase kinase 1 (MEK-1) and mitogen-activated protein kinase kinase kinase 1 (MEKK-1) with potential antipsoriatic and antineoplastic activities. MEK-1/MEKK-1 inhibitor E6201 specifically binds to and inhibits the activities of MEK-1 and MEKK-1, which may result in the inhibition of tumor cell proliferation. MEK-1 and MEKK-1 are key components in the RAS/RAF/MEK/MAPK signaling pathway, which regulates cell proliferation and is frequently activated in human cancers.
An agent targeting cell cycle checkpoint kinase 1 (Chk1) with potential radiosensitization and chemosensitization activities. Chk1 inhibitor MK-8776 specifically binds to and inhibits Chk1, which may result in tumor cells bypassing Chk1-dependent cell cycle arrest in the S and G2/M phases to undergo DNA repair prior to entry into mitosis; tumor cells may thus be sensitized to the DNA-damaging effects of ionizing radiation and alkylating chemotherapeutic agents. Chk1 is an ATP-dependent serine-threonine kinase that in response to DNA damage phosphorylates cdc25 phosphatases, resulting in inhibitory tyrosine phosphorylation of CDK-cyclin complexes and cell cycle arrest.
A protein kinase inhibitor specific for the cyclin-dependent kinase 4 (CDK4) with potential antineoplastic activity. CDK4 inhibitor P1446A-05 specifically inhibits CDK4-mediated G1-S phase transition, arresting cell cycling and inhibiting cancer cell growth. The serine/threonine kinase CDK4 is found in a complex with D-type G1 cyclins and is the first kinase to become activated upon mitogenic stimulation, releasing cells from a quiescent stage into the G1/S growth cycling stage; CDK-cyclin complexes have been shown to phosphorylate the retinoblastoma (Rb) transcription factor in early G1, displacing histone deacetylase (HDAC) and blocking transcriptional repression.
Rearrangement of the PDGFRA gene, resulting in the formation of a fusion transcript and aberrant tyrosine kinase activity. It has been described in hematologic malignancies usually presenting as chronic eosinophilic leukemia.
A synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis. This agent is also a competitive inhibitor of adenosine triphosphate activity.
An orally active, extended-release preparation of the hydrochloride salt of tapentadol with analgesic activity. Tapentadol is a synthetic, centrally acting analgesic with a dual mechanism of action involving mu-opioid receptor agonism and norepinephrine reuptake inhibition. This agent may be effective in the management of pain, cancer-related and other.
A pharmaceutical preparation of adapalene and benzoyl peroxide that is used as a DERMATOLOGIC AGENT for the topical treatment of ACNE.
Victim of an intentional exertion of physical force so as to cause injury, damage or death
Inflammation of the liver related to lipid accumulation in fatty liver.
An area of necrotic bone in the mandible or maxilla.
Time when patient enters the operating or procedure room.
Time the patient arrives in the pre-procedure area of the operating room or procedure room.
Time when personnel begin setting up in the operating or procedure room the supplies and equipment for the next case.
The maleate salt of an indole ether quinazoline derivative with antineoplastic activities. Competing with adenosine triphosphate, cediranib binds to and inhibits all three vascular endothelial growth factor receptor (VEGFR-1,-2,-3) tyrosine kinases, thereby blocking VEGF-signaling, angiogenesis, and tumor cell growth.
Inadequate quantity or quality of personal relations
Lack of ability to exercise restraint or control over feelings, emotions or reactions.
The patient is free from signs and symptoms of surgical site infection such as pain, induration, foul odor, purulent drainage, and/or fever following the perioperative procedure.
An integrated pattern of modulation of the physiological and neurobehavioral systems of functioning, which can be strengthened.
Inspiration of a foreign object into the airway. [HPO:probinson]
An acute, unexplained episode that is frightening to the caretaker and that includes one of the following features: apnea, color change, marked change in muscle tone, choking or gagging.
The lipophilic 5'-elaidic acid ester of the deoxycytidine analog cytosine arabinoside (cytarabine; Ara-C) with potential antineoplastic activity. As a prodrug, elacytarabine is converted intracellularly into cytarabine triphosphate by deoxycytidine kinase and subsequently competes with cytidine for incorporation into DNA, thereby inhibiting DNA synthesis. Compared to cytarabine, elacytarabine shows increased cellular uptake and retention, resulting in increased activation by deoxycytidine kinase to cytarabine triphosphate, decreased deamination and deactivation by deoxycytidine deaminase, and increased inhibition of DNA synthesis. This agent also inhibits RNA synthesis, an effect not seen with cytarabine.
An orally available selective antagonist of the endothelin-A (ET-A) receptor with potential antineoplastic activity. Zibotentan binds selectively to the ET-A receptor, thereby inhibiting endothelin-mediated mechanisms that promote tumor cell proliferation.
A small molecule and non-prodrug analogue of the lipophilic macrolide antibiotic rapamycin with potential antitumor activity. Ridaforolimus binds to and inhibits the mammalian target of rapamycin (mTOR), which may result in cell cycle arrest and, consequently, the inhibition of tumor cell growth and proliferation. Upregulated in some tumors, mTOR is a serine/threonine kinase involved in regulating cellular proliferation, motility, and survival that is located downstream of the PI3K/Akt signaling pathway.
An orally available, 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile irreversible inhibitor of the HER-2 receptor tyrosine kinase with potential antineoplastic activity. Neratinib binds to the HER-2 receptor irreversibly, thereby reducing autophosphorylation in cells, apparently by targeting a cysteine residue in the ATP-binding pocket of the receptor. Treatment of cells with this agent results in inhibition of downstream signal transduction events and cell cycle regulatory pathways; arrest at the G1-S (Gap 1/DNA synthesis)-phase transition of the cell division cycle; and ultimately decreased cellular proliferation. Neratinib also inhibits the epidermal growth factor receptor (EGFR) kinase and the proliferation of EGFR-dependent cells.
A human monoclonal antibody directed against the insulin-like growth factor type I receptor (IGF1R) with potential antineoplastic activity. Figitumumab selectively binds to IGF1R, preventing insulin-like growth factor type 1 (IGF1) from binding to the receptor and subsequent receptor autophosphorylation. Inhibition of IGF1R autophosphorylation may result in a reduction in receptor expression on tumor cells that express IGF1R, a reduction in the anti-apoptotic effect of IGF, and inhibition of tumor growth. IGF1R is a receptor tyrosine kinase expressed on most tumor cells and is involved in mitogenesis, angiogenesis, and tumor cell survival.
A small molecule and a pan-inhibitor of Bcl-2 family proteins, with pro-apoptotic activity. GX015-070 is a selective antagonist of the BH3-binding groove of the Bcl-2 family proteins, which are frequently overexpressed in cancers including chronic lymphocytic leukemia (CLL). This agent induces/restores apoptosis in cancer cells by inhibiting apoptosis suppressors in multiple members of the Bcl-2 family simultaneously.
The hydrochloride salt of the anthracycline derivative berubicin with potential antineoplastic activity. Berubicin intercalates into DNA and interrupts topoisomerase II activity, resulting in the inhibition of DNA replication and repair, and RNA and protein synthesis. Unlike other anthracycline derivatives, this agent crosses the blood-brain barrier (BBB).
The anhydrous form of calcifediol, a hormone precursor that is produced by the hydroxylation of vitamin D in the liver. Calcifediol can be further hydroxylated in the kidney to give calcitriol, the active form of vitamin D. Plasma levels of this compound are measured to determine the vitamin D status of patients.
Marked developmental anomalies of a fetus or infant.
APC-associated polyposis conditions include: familial adenomatous polyposis (FAP), attenuated FAP, and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). FAP is a colon cancer predisposition syndrome in which hundreds to thousands of adenomatous colonic polyps develop, beginning, on average, at age 16 years (range 7-36 years). By age 35 years, 95% of individuals with FAP have polyps; without colectomy, colon cancer is inevitable. The mean age of colon cancer diagnosis in untreated individuals is 39 years (range 34-43 years). Extracolonic manifestations are variably present and include: polyps of the gastric fundus and duodenum, osteomas, dental anomalies, congenital hypertrophy of the retinal pigment epithelium (CHRPE), soft tissue tumors, desmoid tumors, and associated cancers. Attenuated FAP is characterized by multiple colonic polyps (average of 30), more proximally located polyps, and a diagnosis of colon cancer at a later age than in FAP. Certain extracolonic manifestations, such as gastric and duodenal polyps or cancers, are variably present in attenuated FAP; risk management may be substantially different between FAP and attenuated FAP. GAPPS is characterized by gastric fundic gland polyposis, increased risk of gastric cancer, and limited colonic involvement in most individuals reported.
A cholesteryl ester transfer protein (CETP) inhibitor that can produce an increase in serum HDL-cholesterol levels and a decrease in serum LDL-cholesterol levels. Dalcetrapib is structurally dissimilar from other CETP inhibitors, including torcetrapib, and raises functional HDL by a different mechanism.
A small, sac-like aneurysm (outpouching) of a cerebral blood vessel.
An orally available small molecule with activity against orthopoxviruses. Tecovirimat is an inhibitor of viral p37 and blocks the ability of virus particles to be released from infected cells.
A small molecule Syk kinase inhibitor with potential anti-inflammatory and immunomodulating activities. Fostamatinib inhibits Syk kinase-mediated IgG Fc gamma receptor signaling, resulting in inhibition of the activation of mast cells, macrophages, and B-cells and related inflammatory responses and tissue damage. Syk kinase, widely expressed in hematopoietic cells, is a nonreceptor tyrosine kinase that is involved in coupling activated immunoreceptors to signal downstream events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis.
An orally bioavailable adrenal steroid analogue with potential antineoplastic activity. Androstane steroid HE3235 appears to bind the androgen receptor (AR), down-regulating anti-apoptotic genes, such as Bcl-2, while increasing the expression of pro-apoptotic genes, such as caspases. In vitro and in vivo studies indicate that this agent inhibits androstenediol-dependent LNCaP cell tumor growth. In addition, HE3235 may potentiate chemotherapeutic agents by down-regulating ABCG2, the gene encoding the multi-drug resistant (MDR) protein MDR2.
A humanized monoclonal antibody directed against human CD74 with potential antineoplastic activity. Milatuzumab specifically binds to CD74 on CD74-positive cells. Although the exact mechanism through which this agent induces apoptosis is unknown, it may involve antibody-dependent cellular cytotoxicity (ADCC) or complement-mediated cytotoxicity (CMC). Alternatively, as CD74 is the cellular receptor for the cytokine migration-inhibitory factor (MIF), the cytotoxicity of this agent may be related to inhibition of CD74 activation by MIF. CD74, an integral membrane protein that functions as an MHC class II chaperone, may also be an accessory-signaling molecule; activation of CD74 may initiate cell survival mechanisms involving induction of a signaling cascade resulting in NFkB activation, entry of stimulated cells into the S phase of the cell cycle, elevation of DNA synthesis, cell division, and augmented expression of Bcl-xL.
A vaccine consisting of detoxified diphtheria toxoid (D), detoxified tetanus toxoid (T), acellular pertussis (aP) antigens, inactivated poliovirus (IPV) types 1, 2 and 3, and Haemophilus influenzae type b (Hib) capsular polysaccharide (polyribosylribitol phosphate; PRP) covalently bound to tetanus protein, suspended in water for injection and with active immunizing activity against diphtheria, tetanus, pertussis, poliomyelitis and H. influenzae type b. The five purified pertussis antigens in this vaccine are pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and fimbriae types 2 and 3 (FIM). Upon intramuscular injection of the diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis-Haemophilus influenzae type b vaccine (DTaP-IPV-Hib), this vaccine activates the immune system to develop antibodies against diphtheria toxin, tetanus toxin, B. pertussis antigens, polioviruses and Hib, thereby providing active immunization against these diseases. The diphtheria and tetanus toxoids and pertussis antigens (inactivated PT, FHA, PRN and FIM) are adsorbed separately onto aluminum phosphate and then combined with IPV and PRP.
A recombinant immunotoxin consisting of the Fv portion of the anti-CD22 antibody covalently fused to a 38 KDa fragment of Pseudomonas exotoxin-A (PE38) with potential antineoplastic activity. The Fv portion of anti-CD22 immunotoxin CAT-8015 binds to CD22, a cell surface receptor expressed on a variety of malignant B-cells, thereby delivering the toxin moiety PE38 directly to tumor cells. Once internalized, PE38 induces caspase-mediated apoptosis via a mechanism involving mitochondrial damage and blocks translational elongation by binding to elongation factor 2 (EF-2). Anti-CD22 immunotoxin CAT-8015 exhibits a greater affinity for CD22 than its predecessor, anti-CD22 immunotoxin CAT-3888 (BL22 immunotoxin), and hence may be more effective against tumor cells expressing lower levels of CD22.
Antithrombin-III (464 aa, ~53 kDa) is encoded by the human SERPINC1 gene. This protein is involved in the negative regulation of serine proteinase activity during blood coagulation.
Drying and shriveling of the dental pulp due to dry gangrene. Historically this was a method used to remove devitalized pulp.
Loss of CORNEAL ENDOTHELIUM usually following intraocular surgery (e.g., cataract surgery) or due to FUCHS' ENDOTHELIAL DYSTROPHY; ANGLE-CLOSURE GLAUCOMA; IRITIS; or aging.
An arteriopathy characterised by visual loss, progressive or episodic deafness, and abnormal fundoscopy.
A form of presenile DEMENTIA characterized by cortical dementia, NEUROFIBRILLARY TANGLES without SENILE PLAQUES, Fahr's type CALCINOSIS, and ATROPHY in frontotemporal or TEMPORAL LOBE.
An apraxia characterized by the affected limb having involuntary, autonomous, and purposeful behaviors that are perceived as being controlled by an external force. Often the affected limb interferes with the actions of the normal limb. Symptoms develop from lesions in the CORPUS CALLOSUM or medial frontal cortex, stroke, infarction, and neurodegenerative diseases (e.g., CREUTZFELDT-JAKOB SYNDROME, corticobasal degeneration).
A sudden CARDIAC ARRHYTHMIA (e.g., VENTRICULAR FIBRILLATION) caused by a blunt, non-penetrating impact to the precordial region of chest wall. Commotio cordis often results in sudden death without prompt cardiopulmonary defibrillation.
Disjoining the limbs or other parts of a corpse, often in association with criminal acts.
The structural changes in the number, mass, size and/or composition of the airway tissues.
Small airway (e.g., BRONCHIOLES) remodeling due to smoking, inhaled irritants, etc.
The structural changes seen in the asthmatic airways, including increased SMOOTH MUSCLE mass, deposition of EXTRACELLULAR MATRIX components, and thickening of the epithelial reticular BASEMENT MEMBRANE. Asthmatic airway remodeling is often associated with airway function decline (e.g., airflow limitation, persistent airway hyper-responsiveness, and allergic airway inflammation).
A disorder of unknown cause affecting honeybees, whereby a colony rapidly loses its adult bee population. ISRAELI ACUTE PARALYSIS VIRUS OF BEES may have a role in the disorder.
Group of systemic vasculitis with a strong association with ANCA. The disorders are characterized by necrotizing inflammation of small and medium size vessels, with little or no immune-complex deposits in vessel walls.
Genetic variants (specific mutations or allelles of genes) and their corresponding phenotypic variations in the trait or the disease which the genes controls.
Protection conferred on a host by inoculation with one strain or component of a microorganism that prevents infection when later challenged with a similar strain. Most commonly the microorganism is a virus.
DEEP VEIN THROMBOSIS of an upper extremity vein (e.g., AXILLARY VEIN; SUBCLAVIAN VEIN; and JUGULAR VEINS). It is associated with mechanical factors (Upper Extremity Deep Vein Thrombosis, Primary) secondary to other anatomic factors (Upper Extremity Deep Vein Thrombosis, Secondary). Symptoms may include sudden onset of pain, warmth, redness, blueness, and swelling in the arm.
DEEP VEIN THROMBOSIS of an upper extremity vein (e.g., AXILLARY VEIN; SUBCLAVIAN VEIN; and JUGULAR VEINS) that develops as a complication of upper extremity central venous catheters and pacemaker uses, or cancer.
Autosomal dominant inherited disorders characterized by abnormalities of C1 inhibitor. Patients present with swelling of the skin, subcutaneous tissues, and mucosa sites. In type I hereditary angioedema, the plasma levels of C1 inhibitor are decreased. In type II hereditary angioedema, the C1 inhibitor is dysfunctional and its plasma levels may be normal or elevated.
Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by episodic local subcutaneous edema and submucosal edema involving the upper respiratory and gastrointestinal tracts. There are 2 classic types of the disorder. In type I, representing 85% of patients, serum levels of C1NH are less than 35% of normal (Cicardi and Agostoni, 1996; Bowen et al., 2001). In type II, the levels are normal or elevated, but the protein is nonfunctional. The 2 types are clinically indistinguishable. See 300145 for a discussion of angioedema induced by ACE inhibitors. Zuraw (2008) provided a detailed review of the clinical features, management, and pathogenesis of hereditary angioedema.
Rare congenital cardiomyopathies characterized by the lack of left ventricular myocardium compaction. The noncompaction results in numerous prominent trabeculations and a loose myocardial meshwork (spongy myocardium) in the LEFT VENTRICLE. Heterogeneous clinical features include diminished systolic function sometimes associated with left ventricular dilation, that presents either neonatally or progressively. Often, the RIGHT VENTRICLE is also affected. CONGESTIVE HEART FAILURE; PULMONARY EMBOLISM; and ventricular ARRHYTHMIA are commonly seen.
Mutations in the alpha-dystrobrevin gene are associated with Autosomal Dominant type of Noncompaction of the Left Ventricular Myocardium.
Mutations in the tafazzin gene are associated with X-Linked Isolated Noncompaction of the Left Ventricular Myocardium. BARTH SYNDROME is an allelic disorder.
Medicines that are stocked behind the counter of a pharmacy which require the attention or counsel of a pharmacist before being dispensed or handed over to a consumer or patient.
Infections with the protozoa of the phylum EUGLENOZOA.
Condition of low SYSTEMIC VASCULAR RESISTANCE that develops secondary to other conditions such as ANAPHYLAXIS; SEPSIS; SURGICAL SHOCK; and SEPTIC SHOCK. Vasoplegia that develops during or post surgery (e.g., CARDIOPULMONARY BYPASS) is called postoperative vasoplegic syndrome or vasoplegic syndrome.
Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.
A benign adnexal neoplasm derived from cells of the terminal duct of eccrine or apocrine SWEAT GLAND lineage. They typically manifest as solitary papules and occur only in the skin but unlike in ACROSPIROMA involves the epidermis.
Benign adnexal neoplasm whose glandular secretion includes the release of part of the secreting cell.
Asymmetries in the topography and refractive index of the corneal surface that affect visual acuity.
Substances which reduce or eliminate dentinal sensitivity or the pain associated with a source of stimulus (such as touch, heat, or cold) at the orifice of exposed dentinal tubules causing the movement of tubular fluid that in turn stimulates tooth nerve receptors.
Disorders caused by imbalances in the PROTEIN HOMEOSTASIS network - synthesis, folding, and transport of proteins; post-translational modifications; and degradation or clearance of misfolded proteins.
Disorders caused by dysfunctions in PROTEIN FOLDING and degradation or clearance of misfolded proteins.
Diseases characterized by the presence of abnormally phosphorylated, ubiquitinated, and cleaved DNA-binding protein TDP-43 in affected brain and spinal cord. Inclusions of the pathologic protein in neurons and glia, without the presence of AMYLOID, is the major feature of these conditions, thus making these proteinopathies distinct from most other neurogenerative disorders in which protein misfolding leads to brain amyloidosis. Both frontotemporal lobar degeneration and AMYOTROPHIC LATERAL SCLEROSIS exhibit this common method of pathogenesis and thus they may represent two extremes of a continuous clinicopathological spectrum of one disease.
The deletion and reinsertion of a segment of a nucleic acid sequence in the same place, but flipped in an opposite orientation.
Drying and shriveling of the fetus that sometimes occurs after the resorption of fluid following fetal death in veterinary animals.
Hemorrhage caused by vitamin K deficiency.
A rare cutaneous tumor of apocrine or eccrine SWEAT GLAND origin. It is most commonly found on the extremities and is usually benign. It appears as a solitary nodule or cyst and may be solid or produce a watery discharge. It is related to POROMA except in acrospiroma it does not involve the epidermis. There is no indication that heredity or external agents cause these tumors.
Inflammation of the nasal mucosa with nasal congestion.
The acetate form of a long-acting, synthetic peptide with gonadotrophin-releasing hormone (GnRH) antagonistic properties. Degarelix targets and blocks GnRH receptors located on the surfaces of gonadotroph cells in the anterior pituitary, thereby reducing secretion of luteinizing hormone (LH) by pituitary gonadotroph cells and so decreasing testosterone production by interstitial (Leydig) cells in the testes.
A recombinant monoclonal antibody targeting human interleukin-1 beta (IL-1b), with anti-inflammatory and immunomodulating activities. Canakinumab binds IL-1b and prevents the binding of IL-1b to the IL-1 receptor and inhibits IL-1b-mediated signaling. This may suppress inflammatory responses mediated by IL-1b. IL-1b, a proinflammatory cytokine, plays a key role in inflammation.
A benzisoxazole derivative and active metabolite of RISPERIDONE that functions as a DOPAMINE D2 RECEPTOR ANTAGONIST and SEROTONIN 5-HT2 RECEPTOR ANTAGONIST. It is an ANTIPSYCHOTIC AGENT used in the treatment of SCHIZOPHRENIA.
The hydrochloride salt form of saxagliptin, an orally bioavailable, potent, selective and competitive, cyanopyrrolidine-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Saxagliptin is metabolized into an, although less potent, active mono-hydroxy metabolite.
A calcium salt formulation of pitavastatin, a novel statin that induces plaque regression and elevates HDL-cholesterol levels.
sex linked inherited disease characterized by excessive scaling
G6PD deficiency is the most common genetic cause of chronic and drug-, food-, or infection-induced hemolytic anemia. G6PD catalyzes the first reaction in the pentose phosphate pathway, which is the only NADPH-generation process in mature red cells; therefore, defense against oxidative damage is dependent on G6PD. Most G6PD-deficient patients are asymptomatic throughout their life, but G6PD deficiency can be life-threatening. The most common clinical manifestations of G6PD deficiency are neonatal jaundice and acute hemolytic anemia, which in most patients is triggered by an exogenous agent, e.g., primaquine or fava beans. Acute hemolysis is characterized by fatigue, back pain, anemia, and jaundice. Increased unconjugated bilirubin, lactate dehydrogenase, and reticulocytosis are markers of the disorder. The striking similarity between the areas where G6PD deficiency is common and Plasmodium falciparum malaria (see 611162) is endemic provided evidence that G6PD deficiency confers resistance against malaria (summary by Cappellini and Fiorelli, 2008).
Nephropathy due to hypoperfusion of the kidney.
The presence of hemosiderin in the urine.
Glomerulonephritis in the context of Henoch-Schönlein purpura.
A collection of blood between the scalp and the skull periosteum.
Any unfavorable or unintended symptom, sign, or disease including an abnormal laboratory finding) temporally associated with the previous administration of vaccine(s) that may or may not be considered related to the vaccine administration. Such events can be intervention related, dose related, route related, patient related, or caused by an interaction with other product(s) or procedure(s).
A postoperative syndrome, usually presenting after midline posterior fossa tumor resection, that involves a variety of signs and symptoms including aphasia, mutism or speech disturbances, dysphagia, mobility problems, cranial nerve palsies and emotional instability.
Vaginal intraepithelial neoplasia characterized by the presence of moderate or severe dysplastic changes.
O' Sullivan McLeod syndrome is a benign lower motor neuron disorder and a rare variant of monomelic amyotrophy (MA; see this term), characterized by an initial unilateral weakness in the intrinsic hand muscles that eventually spreads to the opposite limb (with an asymmetrical distribution) and that has a very slow progression of muscular atrophy over a 20 year period.
A folate analog consisting of the pharmacologically active isomer of LEUCOVORIN.
An orally bioavailable, acetate salt of ulipristal, a selective progesterone receptor modulator with anti-progesterone activity. Ulipristal binds to the progesterone receptor (PR), thereby inhibiting PR-mediated gene expression, and interfering with progesterone activity in the reproductive system. As a result, this agent may suppress the growth of uterine leiomyomatosis. Furthermore, by inhibiting or delaying ovulation and effecting endometrial tissue, ulipristal can be used as an emergency contraception
A sodium salt form of sulfamerazine, a long-acting sulfanilamide antibacterial agent.
The recombinant form of human antihemophilic factor (AH)) (Factor VIII) with coagulation promoting activity. Antihemophilic factor binds to factor IXa in the coagulation cascade along with calcium and phospholipid. This complex converts factor X to the activated form, factor Xa. In turn, factor Xa/Va complex activates thrombin, which cleaves fibrinogen into fibrin, eventually resulting in blood clot formation.
A hearing disorder characterized by impaired transmission of signals through the auditory nerve, resulting in mild to severe hearing loss and poor speech perception.
An abnormal accumulation of fluid beneath the skin on the back of the hands. [HPO:probinson]
Type I diabetes mellitus in which the blood glucose levels over time are kept within a range such that tests that reflect long-term variation of blood glucose, such as HbA1c, do not exceed limits that are expected to be achieved by available therapies.
Type I diabetes mellitus in which the blood glucose levels over time exceed levels such that tests that reflect long-term variation of blood glucose, such as HbA1c, exceed limits that are expected to be achieved by available therapies.
A subjective feeling of tiredness characterized by a lack of energy and motivation and that is induced by exertion or exercise.
Hypercholesterolaemia in which the blood cholesterol levels over time do not exceed limits that are expected to be achieved by available therapies.
Ductal carcinoma in situ of the breast with minimal stromal invasion. Lymph node involvement is uncommon and the prognosis is generally good.
A polyp that arises from the large intestine and the appendix. It is characterized by the presence of serrated glands and the absence of generalized dysplasia. Some authors have suggested that it is a precursor lesion for some colorectal adenocarcinomas with microsatellite instability.
A tumor (abnormal growth of tissue) of the skeleton.
Type II diabetes mellitus in which the blood glucose levels over time exceed levels such that tests that reflect long-term variation of blood glucose, such as HbA1c, exceed limits that are expected to be achieved by available therapies
Type 2 diabetes mellitus in which the blood glucose levels over time are kept within a range such that tests that reflect long-term variation of blood glucose, such as HbA1c, do not exceed limits that are expected to be achieved by available therapies.
Pathological processes or diseases where cerebral MICROVESSELS show abnormalities. They are often associated with aging, hypertension and risk factors for lacunar infarcts (see LACUNAR INFARCTION); LEUKOARAIOSIS; and CEREBRAL HEMORRHAGE.
Paroxysmal movements, behaviors and sensations similar to a tremor but due to psychological distress instead of a neurological disorder.
A putative Borrelia infection causing acute manifestations similar to Lyme disease, particularly erythema migrans, following the bite of the lone star tick, Amblyomma americanum.
Full-thickness macular hole (FTMH) is defined as a foveal lesion with interruption of all retinal layers from the internal limiting membrane to the retinal pigment epithelium. Full-thickness macular hole is primary if caused by vitreous traction or secondary if directly the result of pathologic characteristics other than vitreomacular traction. Full-thickness macular hole is subclassified by size of the hole as determined by OCT and the presence or absence of vitreomacular traction.
A usually aggressive malignant neoplasm arising from the bone. It is characterized by the presence of spindle-shaped fibroblasts and collagenous stroma formation in a herringbone growth pattern.
A melanoma of the skin characterized by single cell infiltration of the papillary dermis by atypical melanocytes, in a background of lentigo maligna changes.
An orally bioavailable, small-molecule gamma secretase (GS) inhibitorwith potential antitumor activity. Gamma secretase inhibitor RO4929097 binds to GS and blocks activation of Notch receptors, which may inhibit tumor cell proliferation. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth.
A non-steroidal agent with anabolic activity. Selective androgen receptor modulator (SARM) GTx-024 is designed to work like testosterone, thus promoting and/or maintaining libido, fertility, prostate growth, and muscle growth and strength. Mimicking testosterone's action, this agent may increase lean body mass, thereby ameliorating muscle wasting in the hypermetabolic state of cancer cachexia.
A recombinant, fully human monoclonal antibody directed against human vascular endothelial growth factor receptor 2 (VEGFR-2) with antiangiogenesis activity. Ramucirumab specifically binds to and inhibits VEGFR-2, which may result in an inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR-2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells.
A glycoengineered, humanized IgG1 monoclonal antibody with potential antineoplastic activity. Obinutuzumab, a third generation type II anti-CD20 antibody, selectivity binds to the extracellular domain of the human CD20 antigen on malignant human B cells. The Fc region carbohydrates of the antibody, enriched in bisected non-fucosylated glycosylation variants, contribute to its higher binding affinity for human FcgammaRIII receptors compared to non-glycoengineered antibodies, resulting in enhanced antibody-dependent cellular cytotoxicity (ADCC) and caspase-independent apoptosis. In addition, modification of elbow hinge sequences within the antibody variable framework regions may account for the strong apoptosis-inducing activity of R7159 upon binding to CD20 on target cells.
A humanized monoclonal antibody directed against the CD40 receptor with potential antineoplastic activity. Dacetuzumab specifically binds to and inhibits the CD40 receptor, thereby inducing apoptosis and inhibiting cellular proliferation via antibody-dependent cellular cytotoxicity (ADCC) in cells that overexpress this receptor. The CD40 receptor, a member of the tumor necrosis factor (TNF) receptor super-family, is highly expressed on most B lineage hematologic malignancies including multiple myeloma, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's disease and acute lymphoblastic leukemia.
An orally available pan-protein kinase C (PKC) inhibitor with potential immunosuppressive and antineoplastic activities. Sotrastaurin inhibits both T- and B-cell activations via PKC theta and beta isozymes, respectively. Both PKCs are important in the activation of nuclear factor-kappaB (NF-kB). Inhibition of PKC beta in B-cells results in prevention of NF-kB-mediated signaling and down regulation of NF-kB target genes. This may eventually lead to an induction of G1 cell cycle arrest and tumor cell apoptosis in susceptible tumor cells. This agent may act synergistically with other chemotherapeutic agents. PKC, a family of serine/threonine protein kinases overexpressed in certain types of cancer cells, is involved in cell differentiation, mitogenesis, inflammation, and the activation and survival of lymphocytes.
A synthetic benzamide derivative with potential antineoplastic activity. Entinostat binds to and inhibits histone deacetylase, an enzyme that regulates chromatin structure and gene transcription. This agent appears to exert dose-dependent effects in human leukemia cells including cyclin-dependent kinase inhibitor 1A (p21/CIP1/WAF1)-dependent growth arrest and differentiation at low drug concentrations; a marked induction of reactive oxygen species (ROS); mitochondrial damage; caspase activation; and, at higher concentrations, apoptosis. In normal cells, cyclin-dependent kinase inhibitor 1A expression has been associated with cell-cycle exit and differentiation.
A human monoclonal antibody directed against the human interleukins 12 (IL-12) and 23 (IL-23), with immunomodulating activity. Briakinumab binds to both IL-12 and IL-23, which prevents IL-12- and IL-23-mediated signaling. This may suppress immune responses mediated by these interleukins. The cytokines IL-12 and IL-23 play an important role during inflammation.
An orally bioavailable inhibitor of poly (ADP-ribose) polymerase (PARP) types 1 and 2 (PARP-1 and -2), with antineoplastic activity. Upon administration, niraparib binds to and inhibits the activity of PARP-1 and -2, thereby inhibiting PARP-1 and -2-mediated DNA repair, enhancing the accumulation of DNA strand breaks, promoting genomic instability and resulting in apoptosis. The PARP family of proteins catalyzes post-translational ADP-ribosylation of nuclear proteins and is activated by single-strand DNA (ssDNA) breaks.
An agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic activity. Besides its activation of peroxisome proliferator-activated receptor (PPAR) gamma, lobeglitazone is also a potent agonist for PPARalpha.
An orally bioavailable small-molecule inhibitor of Janus kinases 1 and 2 (JAK1/2) with potential antineoplastic activity. JAK1/2 inhibitor CYT387 competes with JAK1/2 for ATP binding, which may result in inhibition of JAK1/2 activation, inhibition of the JAK-STAT signaling pathway, and so the induction of apoptosis and a reduction of tumor cell proliferation in JAK1/2-expressing tumor cells. JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders; the JAK2V617F gain-of-function mutation involves a valine-to-phenylalanine modification at position 617. The JAK-STAT signaling pathway is a major mediator of cytokine activity and is often dysregulated in a variety of tumor cell types.
An oligomeric proanthocyanidin extracted from the latex produced by the tree Croton lechleri (Euphorbiaceae), with antidiarrheal, and potential antiviral and antimicrobial activities. Upon oral administration, crofelemer acts locally within the gastrointestinal (GI) tract by inhibiting both the cystic fibrosis transmembrane conductance regulator (CFTR) chloride ion (Cl-) channel and the calcium-activated Cl- channel (CaCC) expressed on the luminal surface of enterocytes. This inhibits the secretion of chloride ions into the intestinal lumen and prevents high volume water loss. By normalizing Cl- and water balance in the intestines, crofelemer relieves secretory diarrhea.
A radioimmunoconjugate containing the recombinant humanized monoclonal antibody trastuzumab conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and labeled with the radioisotope copper Cu 64 with radioisotopic activity and potential use as an imaging agent. The trastuzumab moiety of copper Cu 64-DOTA-trastuzumab binds with high affinity to the extracellular domain of human epidermal growth factor receptor 2 (HER2). Upon binding, the radioisotope moiety may be detected using positron emission tomography (PET), thereby allowing the imaging and quantification of HER2-expressing tumor cells. HER2, a tyrosine kinase and client protein of heat shock protein 90 (Hsp90), may be overexpressed on the cell surfaces of various tumor cell types.
A soft gelatin capsule formulation containing the meglumine salt form of tafamidis, a small molecule and pharmacological chaperone with potential disease-modifying activity. Tafamidis binds to and stabilizes wild-type and variant (V122I) transthyretin (TTR), thereby preventing tetramer dissociation into monomers; this prevents misfolding of the TTR protein and inhibits the formation of TTR amyloid fibrils and the subsequent deposition of these insoluble protein clusters in peripheral nerve tissues and organs. TTR is a 127 amino acid transport protein for thyroxine and retinol and is secreted by the liver.
A low molecular weight polymer-conjugated platinum complex with potential antineoplastic activity. This polymer drug delivery system consists of cytotoxic diaminocyclohexane (DACH)-platinum (Pt) coupled to a water-soluble biocompatible hydroxypropylmethacrylamide (HPMA) copolymer via a pH sensitive linker. Due to decreased pH at the tumor site, the linker is cleaved and the chelated active moiety DACH-Pt is released in tumor cells. DACH-Pt alkylates macromolecules and causes both inter- and intra-strand platinum-DNA crosslinks, which impede DNA replication and transcription, thereby resulting in cell-cycle independent cytotoxicity. The HPMA-based drug delivery system enhances the concentration of DACH-Pt at the tumor site and prolongs the half life of the agent, thereby increasing exposure and efficacy at the target tumor sites while minimizing side effects in normal tissues.
Inherited systemic hyalinosis is characterized by hyaline deposits in the papillary dermis and other tissues. It typically presents at birth or in infancy with severe pain with movement, progressive joint contractures, and often with severe motor disability, thickened skin, and hyperpigmented macules/patches over bony prominences of the joints. Gingival hypertrophy, skin nodules, pearly papules of the face and neck, and perianal masses are common. Complications of protein-losing enteropathy and failure to thrive can be life threatening. Cognitive development is normal. Many children with the severe form (previously called infantile systemic hyalinosis) die in early childhood; some with a milder phenotype (previously called juvenile hyaline fibromatosis) survive into adulthood.
Odontochondrodysplasia is characterized by mesomelic shortening of tubular bones, ligamentous laxity, and scoliosis, in association with dentinogenesis imperfecta involving both primary and secondary dentition. Affected individuals show variable severity. Radiologic features include trident pelvis, posteriorly flattened vertebrae, and brachydactyly with cone-shaped epiphyses (Maroteaux et al., 1996). Clinical variability and extraskeletal manifestations have been observed (Wehrle et al., 2019). Mutation in the TRIP11 gene also causes a more severe chondrodysplasia, achondrogenesis type IA (ACG1A; 200600).
Spondyloepiphyseal dysplasia congenita is an autosomal dominant chondrodysplasia characterized by disproportionate short stature (short trunk), abnormal epiphyses, and flattened vertebral bodies. Skeletal features are manifested at birth and evolve with time. Other features include myopia and/or retinal degeneration with retinal detachment and cleft palate (summary by Anderson et al., 1990).
Disabling osteochondrodysplasia with OSTEOSCLEROSIS, cone-shaped METAPHYSIS, and shortening of the DIAPHYSIS. It is endemic in parts of Siberia and northern China. Mineral deficiencies (e.g., selenium, iodine), fungal cereal contamination, and water contamination may be contributing factors in its etiology.
Situations or conditions requiring immediate intervention to avoid serious adverse results.
This syndrome has characteristics of intellectual deficit, spasticity in the lower limbs (spastic paraplegia), pes cavus deformity of both feet, an abnormal gait, and palmar and plantar hyperkeratosis. It has been reported in four brothers. The mother of the affected boys had normal intelligence, plantar hyperkeratosis and a strong facial resemblance to her retarded sons. Her three daughters were normal. This syndrome most likely an X-linked recessive condition.
Orofaciodigital syndrome type VI (OFD6), or Varadi syndrome, is a rare autosomal recessive disorder distinguished from other orofaciodigital syndromes by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities, including the molar tooth sign (summary by Doss et al., 1998 and Lopez et al., 2014).
Any substance that inhibits ribonucleotide reductase, an enzyme that catalyzes the conversion of ribonucleoside diphosphates to deoxyribonucleotide diphosphate precursors for de novo DNA synthesis. Inhibition of ribonucleotide reductase can cause inhibition of DNA synthesis and cell growth.
Any substance that inhibits adenosine deaminase, an enzyme involved with the degradation of adenine in purine metabolism and that acts as a positive regulator of T-cell coactivation.
Any substance that inhibits DNA methyltransferase, an enzyme required for DNA methylation. Inhibition of DNA methyltransferase results in hypomethylation of genomic DNA and cell cycle arrest at S-phase. Hypomethylation in malignant cells may also restore suppressor gene expression and re-establish controlled growth and differentiation.
Any substance that inhibits DNA polymerase, an enzyme that catalyzes the addition of deoxyribonucleotide residues to the end of a DNA molecule. Inhibition of DNA polymerase causes an inhibition of DNA synthesis and results in cell cycle arrest.
Any substance that inhibits mammalian target of rapamycin (mTOR or FK506 binding protein 12-rapamycin associated protein 1 (FRAP1)), a serine/threonine protein kinase that is active in the control of cell growth, cell proliferation, and cell motility. Inhibition of mTOR can inhibit cell proliferation.
A humanized monoclonal antibody directed against the CD20 antigen with potential antineoplastic activity. Following binding, veltuzumab triggers complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) in cells that overexpress CD20. CD20 antigen is a hydrophobic transmembrane protein located on pre-B and mature B lymphocytes.
A synthetic lipid-conjugated, 13-mer oligonucleotide N3'-P5'-thio-phosphoramidate with potential antineoplastic activity. Complementary to the template region of telomerase (hTR) RNA, imetelstat acts as a competitive enzyme inhibitor that binds and blocks the active site of the enzyme (a telomerase template antagonist), a mechanism of action which differs from that for the antisense oligonucleotide-mediated inhibition of telomerase activity through telomerase mRNA binding. Inhibition of telomerase activity in tumor cells by imetelstat results in telomere shortening, which leads to cell cycle arrest or apoptosis.
Combined D-2- and L-2-hydroxyglutaric aciduria (D-2-HG and L-2-HG) is an autosomal recessive neurometabolic disorder characterized by neonatal-onset encephalopathy with severe muscular weakness, intractable seizures, respiratory distress, and lack of psychomotor development resulting in early death. Brain imaging shows abnormalities including enlarged ventricles, delayed myelination, and germinal layer cysts (summary by Muntau et al., 2000). See also isolated L-2-hydroxyglutaric aciduria (236792) and isolated D-2-hydroxyglutaric aciduria (see 600721).
Chronic idiopathic intestinal pseudoobstruction (CIIP) is caused by severe abnormality of gastrointestinal motility. Patients have recurrent symptoms and signs of intestinal obstruction without any mechanical lesion (Auricchio et al., 1996). Some primary forms of CIIP are caused by defects of enteric neuronal cells: see Hirschsprung disease (see, e.g., HSCR1; 142623) and autosomal recessive visceral neuropathy (243180) (Tanner et al., 1976).
Any of the synthetic agents that bind to somatostatin receptors and mimic the actions of somatostatin.
Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.
A potent, orally bioavailable dihydropurinedione-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. The inhibition of DPP-4 by linagliptin appears to be longer lasting than that by some other DPP-4 inhibitors tested.
A cancer vaccine consisting of a recombinant form of human melanoma antigen A3 (MAGE-A3) combined with a proprietary adjuvant with potential immunostimulatory and antineoplastic activities. Upon administration, astuprotimut-R may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the MAGE-A3 antigen, resulting in tumor cell death. MAGE-A3, a tumor-associated antigen (TAA) originally discovered in melanoma cells, is expressed by various tumor types. The proprietary immunostimulating adjuvant in this agent is composed of a specific combination of immunostimulating compounds selected to increase the anti-tumor immune response to MAGE-A3.
Acute malaria with signs of organ dysfunction, severe anemia (hemoglobin less than 5 g/dL or hematocrit less than 15%) and/or hyperparasitemia (greater than 5% of red blood cells infected).
Sudden occurrence of BRADYCARDIA or HEART ARREST induced by manipulations of the MAXILLARY NERVE AND MANDIBULAR NERVE during a craniomaxillofacial or oral surgery. It is the maxillary and mandibular variants of OCULOCARDIAC REFLEX.
A decreased concentration of insulin in the blood.
Perifoveal vitreous separation with remaining vitreomacular attachment and unperturbed foveal morphologic features. It is an OCT finding that is almost always the result of normal vitreous aging, which may lead to pathologic conditions.
Increased susceptibility to infection by the protozan parasite of the genus Leishmania.
A very rare form of stromal corneal dystrophy with characteristics of irregular amorphous sheet-like opacities in the posterior corneal stroma and in the Descemet membrane along with mildly impaired vision. Prevalence of this form of corneal dystrophy is not known. To date cases have been reported primarily in the USA. Patients usually develop corneal abnormalities in infancy or childhood. The condition is non-progressive or slowly progressive. Unlike other corneal dystrophies, non-corneal manifestations have been observed and include abnormalities of the iris including iridocorneal adhesions, corectopia, and pseudopolycoria. An autosomal dominant pattern of inheritance has been reported.
A very rare form of superficial corneal dystrophy with characteristics of frequent recurrent corneal erosions in the first decade of life and progressive loss of vision. The condition has only been reported in one single family. Painful episodes of recurrent corneal erosions occur in the first decade of life but decrease during adolescence. Later in life, patients are reported to develop subepithelial opacities and a corneal haze. The disease eventually progresses over time leading to corneal opacities and loss of vision. The gene related to this disease has not been mapped to a particular chromosomal locus.
An autoinflammatory disease caused by mutations in the IL1RN gene, which encodes the IL1 receptor antagonist. It presents in infancy, and is characterized by systemic inflammation, pustular rash, bone pain, sterile osteitis, and periostitis.
This form of brachyolmia, here designated brachyolmia type 4, is characterized by short-trunk stature with normal intelligence and facies. The radiographic features include rectangular vertebral bodies with irregular endplates and narrow intervertebral discs, precocious calcification of rib cartilages, short femoral neck, mildly shortened metacarpals, and mild epiphyseal and metaphyseal changes of the tubular bones (summary by Miyake et al., 2012).
Keratosis follicularis spinulosa decalvans (KFSD) is an uncommon genodermatosis characterized by follicular hyperkeratosis, progressive cicatricial alopecia, and photophobia. Most reported cases show X-linked inheritance (KFSDX; 308800) (Castori et al., 2009).
Presence of excess fibrous connective tissue surrounding hair follicules.
Leukocyte adhesion deficiency-3 (LAD3), also known as LAD1 variant (LAD1V), is an autosomal recessive disorder characterized by LAD1 (116920)-like immune deficiency and Glanzmann thrombasthenia (GT; 273800)-like bleeding problems. LAD3 results from mutations in FERMT3, or KINDLIN3, which encodes an intracellular protein that interacts with beta-integrins in hematopoietic cells. In LAD3, the adhesive functions of integrins on both leukocytes and platelets are disrupted, most likely due to defects in activation-dependent alterations of surface integrins that enable high-avidity binding to ligands on target cells, a process termed 'inside-out signaling' (Svensson et al., 2009; Zimmerman, 2009).
A new form of skeletal dysplasia with manifestations of severe short stature, facial dysmorphism and characteristic radiographic findings. To date, three cases have been described, all originating from the same family. The disease results from a missense mutation affecting the C-type lectin domain of aggrecan (AGC1 gene; chromosome 15) which regulates endochondral ossification. Transmission is autosomal recessive.
Question mark ear is an auricular abnormality characterized by a cleft between the lobule and the lower part of the helix, sometimes accompanied by a prominent or deficient upper part of the helix, shallow skin dimple on the posterior surface of the ear, or transposition of the ear lobe/antitragus. It is more prevalent among boys than girls (2:1), usually sporadic, and can be unilateral or bilateral (Shkalim et al., 2008).
Polyunsaturated fatty acids (PUFA), particularly those of the n-3 or omega-3 family, have been associated with decreased risk of cardiovascular and other chronic diseases (Tanaka et al., 2009).
Immunodeficiency-10 is an autosomal recessive primary immunodeficiency characterized by onset of recurrent infections in childhood due to defective T- and NK-cell function, although the severity is variable. Affected individuals may also have hypotonia, hypohidrosis, or dental enamel hypoplasia consistent with amelogenesis imperfecta (summary by Parry et al., 2016).
Immunodeficiency-9 is an autosomal recessive disorder characterized by early onset of recurrent infections due to defective T-cell activation. Affected individuals also have congenital myopathy resulting in muscle weakness as well as features of ectodermal dysplasia, including soft dental enamel (summary by McCarl et al., 2009).
IGHD type IB is an autosomal recessive disorder characterized by low but detectable levels of GH, short stature (more than 2 SD below the mean for age and sex), delayed bone age, and a good response to rhGH treatment without antibody formation (summary by Alatzoglou et al., 2014). For general phenotypic information and a discussion of genetic heterogeneity of IGHD, see 262400.
Syndrome with characteristics of seizures, sensorineural deafness, ataxia, intellectual deficit, and electrolyte imbalance. It has been described in five patients from four families. The disease is caused by homozygous or compound heterozygous mutations in the KCNJ10 gene, encoding a potassium channel expressed in the brain, spinal cord, inner ear and kidneys. Transmission is autosomal recessive.
An abnormally increased sodium concentration in the urine in the presence of hyponatremia.
Hypoglossia with situs inversus is a very rare congenital condition that likely represents a developmental field defect. Only sporadic cases have been reported (Faqeih et al., 2008). Hypoglossia is part of a group of malformation syndromes collectively termed 'oromandibular limb hypogenesis syndromes,' that usually include limb defects. Hall (1971) provided a classification system (see 103300). See also agnathia with holoprosencephaly (202650), which shows hypoglossia and situs inversus in addition to severe neurodevelopmental defects.
Mitchell-Riley syndrome is characterized by neonatal diabetes, pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia or hypoplasia. There is considerable phenotypic overlap between Mitchell-Riley syndrome and Martinez-Frias syndrome (601346), the latter being characterized by the features of the Mitchell-Riley syndrome except for neonatal diabetes, and including tracheoesophageal fistula in some patients (Smith et al., 2010).
Decreased length of the eyelashes (subjective).
The formation of tissue in the lumen of the jejunum that results in partial obstruction.
Vitamin D-dependent rickets type 2B with normal vitamin D receptor (VDDR2B) is an unusual form of rickets due to abnormal expression of a hormone response element-binding protein that interferes with the normal function of the vitamin D receptor. Vitamin D-dependent rickets type 2A (VDDR2A) is caused by mutation in the vitamin D receptor gene (VDR; 601769), and most patients have alopecia in addition to rickets. For a general phenotypic description and a discussion of genetic heterogeneity of rickets due to disorders in vitamin D metabolism or action, see vitamin D-dependent rickets type 1A (VDDR1A; 264700).
Nonsyndromic 46,XX testicular disorders of sex development (46,XX testicular DSD) are characterized by the presence of a 46,XX karyotype; male external genitalia ranging from normal to ambiguous; two testicles; azoospermia; and absence of müllerian structures. Approximately 85% of individuals with nonsyndromic 46,XX testicular DSD present after puberty with normal pubic hair and normal penile size but small testes, gynecomastia, and sterility resulting from azoospermia. Approximately 15% of individuals with nonsyndromic 46,XX testicular DSD present at birth with ambiguous genitalia. Gender role and gender identity are reported as male. If untreated, males with 46,XX testicular DSD experience the consequences of testosterone deficiency.
Individuals with 46,XY complete gonadal dysgenesis are phenotypically female; however, they do not develop secondary sexual characteristics at puberty and do not menstruate. They have bilateral 'streak gonads,' which typically consist of fibrous tissue and variable amounts of wavy ovarian stroma. A uterus and fallopian tube are present and external genitalia are female (reviewed by Berkovitz et al., 1991). Genetic Heterogeneity of 46,XY Sex Reversal Male sexual determination is initiated by Y-chromosomal SRY, which activates a cascade of genes that lead the embryonic gonad to develop into a testis. Fetal testicular Sertoli cells then produce mullerian inhibitory substance (600957), which is responsible for the involution of the mullerian ducts, which would otherwise develop into the uterus, fallopian tubes, and cervix. Fetal testicular Leydig cells produce testosterone from cholesterol by the sequential action of a series of enzymes. Subsequent differentiation of male external genitalia also requires the action of dihydrotestosterone, produced from testicular testosterone. Perturbations in the enzymes in this classic pathway or in an alternative pathway of testicular androgen biosynthesis can result in genetic males with disordered sexual development and incompletely developed ('ambiguous') external genitalia (summary by Fluck et al., 2011). Disorders of male development for which a genetic cause has been found include 46,XY sex reversal-2 (SRXY2; 300018), which is caused by duplication of the NR0B1 gene (300473) on chromosome Xp21.3-p21.2; SRXY3 (612965), caused by mutation in the NR5A1 gene (184757) on chromosome 9q33; SRXY4 (154230), caused by deletion on chromosome 9p24.3; SRXY5 (613080), caused by mutation in the CBX2 gene (602770) on chromosome 17q25; SRXY6 (613762), caused by mutation in the MAP3K1 gene (600982) on chromosome 5q11.2; SRXY7 (233420), caused by mutation in the DHH gene (605423) on chromosome 12q13; SRXY8 (614279), caused by mutation in the AKR1C2 gene (600450) on chromosome 10p15, with a possible contribution from the closely linked AKR1C4 gene (600451); SRXY9 (616067), caused by mutation in the ZFPM2 gene (603693) on chromosome 8q23; and SRXY10 (616425), caused by deletion of the XYSR regulatory region -640 kb upstream of the SOX9 gene (608160) on chromosome 17q24. Wilhelm and Koopman (2006) reviewed male sexual development and the genetics of disorders of human sexual development, noting that most cases of XY sex reversal, SRY-negative XX sex reversal, and true hermaphroditism remained unexplained at the molecular level.
A neurodevelopmental disorder that is diagnosed when a child presents with a Rett-like syndrome but does not fulfil all the diagnostic criteria for typical Rett syndrome. Several subvariants have been defined; the early-onset seizure type (Hanefeld), congenital variant (Rolando), the 'forme fruste' type, the late childhood regression form and the preserved speech variant (PSD or Zappella variant). Diagnosis relies on clinical evaluation using the diagnostic criteria for atypical Rett originally defined by Hagberg in 1994: an atypical case must meet at least three of the six main criteria and at least five of the eleven supportive criteria.
The int22h1/int22h2-mediated Xq28 duplication syndrome is a recently recognized X-linked intellectual disability syndrome characterized in males by cognitive impairment, behavioral and psychiatric problems, recurrent infections and atopic diseases, obesity, and distinctive facial features. Females heterozygous for this duplication exhibit a milder phenotype (with learning difficulties and distinctive facies) or are clinically unaffected. To date 26 individuals (14 males and 12 females) with this recurrent duplication have been described.
A rare subtype of posterior corneal dystrophy with characteristics of congenital ground glass corneal clouding or a diffuse corneal haze, and blurred vision in male patients. Prevalence of this rare corneal dystrophy is unknown. Males are affected more severely than females. The condition is progressive in males and non-progressive in females. Has been mapped to the long arm of the X-chromosome (Xq25) but the causative gene has not been identified. Transmission is X-linked recessive.
A very rare form of superficial corneal dystrophy with characteristics of feather-shaped opacities and microcysts in the corneal epithelium arranged in a band-shaped and sometimes whorled pattern, occasionally with impaired vision. Exact prevalence of this form of corneal dystrophy is not known but very few cases have been reported to date. Lesions generally develop in childhood. Epithelial opacities are slowly progressive and painless blurred vision sometimes occurs after 60 years of age. The exact cause is unknown but appears to be genetic. The gene related to Lisch epithelial corneal dystrophy has been mapped to the short arm of the X chromosome (Xp22.3).
Underdevelopment of the paranasal sinuses.
An anomaly of the muscular contractions that propel food though the gastrointestinal tract.
Prominent positioning of the premaxilla in relation to the rest of the maxilla, the facial skeleton, or mandible. Not necessarily caused by an increase in size (hypertrophy of) the premaxilla.
A small/hypoplastic or absent/aplastic radius.
ALK-related neuroblastic tumor susceptibility is characterized by increased risk for neuroblastic tumors including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Neuroblastoma is a more malignant tumor and ganglioneuroma a more benign tumor. Depending on the histologic findings, ganglioneuroblastoma can behave in a more aggressive fashion, like neuroblastoma, or in a benign fashion, like ganglioneuroma. Preliminary data from the ten reported families with ALK-related neuroblastic tumor susceptibility suggest an overall penetrance of approximately 57% with the risk for neuroblastic tumor development highest in infancy and decreasing by late childhood.
Segmental or global glomerulopathy with tuft wrinkling, collapse and contraction without increased matrix or cells, but with adjacent podocyte hypertrophy and hyperplasia.
Autosomal recessive congenital methemoglobinemia is an inherited condition that mainly affects the function of red blood cells. Specifically, it alters a molecule within these cells called hemoglobin. Hemoglobin carries oxygen to cells and tissues throughout the body. In people with autosomal recessive congenital methemoglobinemia, some of the normal hemoglobin is replaced by an abnormal form called methemoglobin, which is unable to deliver oxygen to the body's tissues. As a result, tissues in the body become oxygen deprived, leading to a bluish appearance of the skin, lips, and nails (cyanosis).There are two forms of autosomal recessive congenital methemoglobinemia: types I and II. People with type I have cyanosis from birth and may experience weakness or shortness of breath related to the shortage of oxygen in their tissues. People with type II have cyanosis as well as severe neurological problems. After a few months of apparently normal development, children with type II develop severe brain dysfunction (encephalopathy), uncontrolled muscle tensing (dystonia), and involuntary limb movements (choreoathetosis); also, the size of their head remains small and does not grow in proportion with their body (microcephaly). People with type II have severe intellectual disability; they can recognize faces and usually babble but speak no words. They can sit unassisted and grip objects but have impaired motor skills that leave them unable to walk. In type II, growth is often slowed. Abnormal facial muscle movements can interfere with swallowing, which can lead to feeding difficulties and further slow growth.People with autosomal recessive congenital methemoglobinemia type I have a normal life expectancy, but people with type II often do not survive past early adulthood.
An abnormal appearance of the long bones with resemblance to a dumbbell, a short bar with a weight at each end. That is, the long bone is shortened and displays flaring (widening) of the metaphyses.
Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. The onset of atypical HUS (aHUS) ranges from the neonatal period to adulthood. Genetic aHUS accounts for an estimated 60% of all aHUS. Individuals with genetic aHUS frequently experience relapse even after complete recovery following the presenting episode; 60% of genetic aHUS progresses to end-stage renal disease (ESRD).
Progressive impairment of function of motor axons with muscle weakness, atrophy, and cramps. The deficits are length-dependent, meaning that muscles innervated by the longest nerves are affected first, so that for instance the arms are affected at a later age than the onset of deficits involving the lower leg.
A type of megaloblastic anemia (i.e., anemia characterized by the presence of erythroblasts that are larger than normal) that improves upon the administration of folate.
Split-hand/split-foot malformation (SHFM) is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting (Elliott and Evans, 2006). For a general phenotypic description and a discussion of genetic heterogeneity of split-hand/foot malformations, see SHFM1 (183600).
An abnormal reduction of the number and complexity of the pattern of gyrations of the cerebral cortex.
Glycosylated transferrin concentrations can be measured in serum as a marker of N-linked glycosylation fidelity. In the traditional nomenclature for congenital disorders of glycosylation, absence of entire glycans was designated type I, and loss of one or more monosaccharides as type II. These terms are retained for historical reasons but for new annotations the precise glycosylation defect should be recorded.
RRM2B-related mitochondrial disease can be grouped by disease pathogenesis, phenotype, and mode of inheritance into two major types: mitochondrial DNA (mtDNA) depletion and multiple mtDNA deletions. Mitochondrial DNA depletion usually manifests as severe multisystem disease (encephalomyopathy with proximal renal tubulopathy) and is often fatal in early life. Inheritance is autosomal recessive. Multiple mtDNA deletions cause tissue-specific cytochrome c oxidase (COX) deficiency. Inheritance can be either autosomal recessive (with progressive external ophthalmoplegia [PEO] and multisystem involvement manifesting during early childhood/adulthood) or autosomal dominant (with less severe, often tissue-specific manifestations [e.g., chronic PEO] developing in later adulthood). Other rarer phenotypes are Kearns-Sayre syndrome (KSS) and mitochondrial neurogastrointestinal encephalopathy (MNGIE).
SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterized by onset of the following features in infancy or childhood (median age of onset 2 months; range of onset birth to 6 years): psychomotor retardation, hypotonia, dystonia, muscular atrophy, sensorineural hearing impairment, postnatal growth retardation, and feeding difficulties. Other, less frequent, features include distinctive facial features, contractures, kyphoscoliosis, gastroesophageal reflux, ptosis, choreoathetosis, ophthalmoplegia, and epilepsy (infantile spasms or generalized convulsions). The median survival is 20 years; approximately 30% of affected individuals succumb during childhood. Affected individuals may have hyperintensities in the basal ganglia, cerebral atrophy, and leukoencephalopathy on head MRI. Elevation of methylmalonic acid (MMA) in the urine and plasma is found in a vast majority of affected individuals, although at levels that are far below those typically seen in individuals with classic methylmalonic aciduria.
Childhood absence epilepsy is a subtype of idiopathic generalized epilepsy. For a general phenotypic description and a discussion of genetic heterogeneity of childhood absence epilepsy and idiopathic generalized epilepsy, see ECA1 (600131) and (600669), respectively.
3q29 microduplication syndrome (also known as 3q29 duplication syndrome) is a condition that results from the copying (duplication) of a small piece of chromosome 3 in each cell. The duplication occurs on the long (q) arm of the chromosome at a position designated q29.The features associated with 3q29 microduplication syndrome vary widely. Some individuals with this chromosomal change have very mild or no related signs and symptoms, and the duplication is discovered because they undergo genetic testing only after a family member is diagnosed. Other people with a 3q29 microduplication have delayed development (particularly speech delay) and intellectual disability or learning difficulties. Although most affected individuals have no major birth defects, eye abnormalities, heart defects, and an unusually small head (microcephaly) can occur. 3q29 microduplication syndrome may increase the likelihood of being overweight or obese, although it is hard to determine whether these weight issues are caused by the duplication.
Spastic paraplegia-18 is a severe autosomal recessive neurologic disorder characterized by onset in early childhood of progressive spastic paraplegia resulting in motor disability. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures (summary by Alazami et al., 2011 and Yildirim et al., 2011).
Thyrotoxic periodic paralysis is a sporadic muscle disorder characterized by episodic attacks of weakness associated with hypokalemia in individuals with hyperthyroidism. The paralysis resolves upon treatment of hyperthyroidism. The disorder is most common among males of Asian descent, including Chinese, Japanese, Vietnamese, Filipino, and Koreans, although it occurs less commonly in individuals of Caucasian background. Thyrotoxic periodic paralysis is clinically similar to hereditary hypokalemic periodic paralysis (HOKPP; 170400), but the paralysis in TTPP occurs only in the presence of hyperthyroidism. TTPP can also be precipitated by factors that result in hypokalemia, such as carbohydrate ingestion and rest after exercise (review by Kung, 2006). Genetic Heterogeneity of Thyrotoxic Periodic Paralysis See also TTPP2 (613239), conferred by variation in the KCNJ18 gene (613236) on chromosome 17p11, and TTPP3 (614834), mapped to chromosome 17q24.
Emery-Dreifuss muscular dystrophy is characterized classically by the triad of weakness of the shoulder and pelvic girdle muscles, contractures of the elbows, neck, and Achilles tendon, and cardiac involvement, most commonly arrhythmias (summary by Jimenez-Escrig et al., 2012). For a discussion of genetic heterogeneity of EDMD, see 310300.
Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis, whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). For a general phenotypic description and a discussion of genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000.
Spondylo-megaepiphyseal-metaphyseal dysplasia is a rare autosomal recessive skeletal dysplasia characterized by disproportionate short stature with a short and stiff neck and trunk; relatively long limbs that may show flexion contractures of the distal joints; delayed and impaired ossification of the vertebral bodies and the presence of large epiphyseal ossification centers and wide growth plates in the long tubular bones; and numerous pseudoepiphyses of the short tubular bones in hands and feet (summary by Hellemans et al., 2009).
Untreated complete plasminogen activator inhibitor 1 (PAI-1) deficiency is characterized by mild to moderate bleeding, although in some instances bleeding can be life threatening. Most commonly, delayed bleeding is associated with injury, trauma, or surgery; spontaneous bleeding does not occur. While males and females with complete PAI-1 deficiency are affected equally, females may present more frequently with clinical manifestations or earlier in life than males due to menorrhagia and postpartum hemorrhage. Fewer than ten families with complete PAI-1 deficiency have been reported to date. The incidence of complete PAI-1 deficiency is higher than expected in the genetic isolate of the Old Order Amish population of eastern and southern Indiana due to a pathogenic founder variant. In one family from this Old Order Amish population, seven individuals had cardiac fibrosis ranging from minimal-to-moderate (6 individuals) to severe (1).
Congenital generalized lipodystrophy type 4 combines the phenotype of classic Berardinelli-Seip lipodystrophy (608594) with muscular dystrophy and cardiac conduction anomalies (Hayashi et al., 2009). For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594).
Hereditary hypophosphatemic rickets is a disorder related to low levels of phosphate in the blood (hypophosphatemia). Phosphate is a mineral that is essential for the normal formation of bones and teeth.In most cases, the signs and symptoms of hereditary hypophosphatemic rickets begin in early childhood. The features of the disorder vary widely, even among affected members of the same family. Mildly affected individuals may have hypophosphatemia without other signs and symptoms. More severely affected children experience slow growth and are shorter than their peers. They develop bone abnormalities that can interfere with movement and cause bone pain. The most noticeable of these abnormalities are bowed legs or knock knees (a condition in which the lower legs are positioned at an outward angle). These abnormalities become apparent with weight-bearing activities such as walking. If untreated, they tend to worsen with time.Other signs and symptoms of hereditary hypophosphatemic rickets can include premature fusion of the skull bones (craniosynostosis) and dental abnormalities. The disorder may also cause abnormal bone growth where ligaments and tendons attach to joints (enthesopathy). In adults, hypophosphatemia is characterized by a softening of the bones known as osteomalacia.Researchers have described several forms of hereditary hypophosphatemic rickets, which are distinguished by their pattern of inheritance and genetic cause. The most common form of the disorder is known as X-linked hypophosphatemic rickets (XLH). It has an X-linked dominant pattern of inheritance. X-linked recessive, autosomal dominant, and autosomal recessive forms of the disorder are much rarer.Another rare type of the disorder is known as hereditary hypophosphatemic rickets with hypercalciuria (HHRH). In addition to hypophosphatemia, this condition is characterized by the excretion of high levels of calcium in the urine (hypercalciuria).
Primary bile acid malabsorption is an intestinal disorder associated with chronic watery diarrhea, excess fecal bile acids, and steatorrhea. Bile acid malabsorption has been classified into 3 main types depending on the etiology. Types 1 and 3 are secondary disorders: type 1 is due to ileal dysfunction resulting from Crohn disease or ileal resection, and type 3 is secondary to other conditions, including cholecystectomy, post-vagotomy, celiac disease, and pancreatic insufficiency. Type 2 bile acid malabsorption is a primary congenital disorder, including the rare type due to mutations in the SLC10A2 gene (review by Pattni and Walters, 2009).
Cisplatin is a highly effective chemotherapeutic agent, but its use is restricted by the high incidence of irreversible ototoxicity associated with it. This ototoxicity causes serious permanent bilateral hearing loss in 10 to 25% of adults receiving the drug, and in up to 60% of children. The consequences of this ototoxicity are particularly serious in children, because even mild hearing loss can compromise language and cognitive development. Cisplatin ototoxicity frequently leads to dose reduction and premature termination of cisplatin treatment, which may affect overall survival rates (summary by Ross et al., 2009).
Herpes simplex virus (HSV)-1 is most often associated with infection of the oral mucosa. Primary infection is most commonly asymptomatic, but it may lead to symptoms usually involving the mucosa and skin. Following replication at the infection site, HSV-1 enters the epithelial endings of sensory neurons and travels up the trigeminal cranial nerves to the trigeminal ganglia, where latent infection is established. Reactivation of HSV-1, usually in the form of herpes labialis (cold sores), may occur in 20 to 40% of the population. HSV-1 seroprevalence is high, with over 85% of adults between the ages of 20 and 40 years infected. HSV-1 rarely infects the central nervous system (CNS), resulting in herpes simplex encephalitis (HSE), with an incidence of 2 to 4 per 1,000,000 people per year. In HSE, HSV-1 invades and replicates in neurons and glial cells, where focal necrotizing infections occur, primarily affecting the temporal and subfrontal regions of the brain. Untreated, HSE is fatal in at least 70% of cases, although the mortality and morbidity have been drastically reduced with antiviral therapy. Approximately one-third of all HSE cases are due to primary infections, and 30% of all HSE cases occur in children under the age of 20 years. Among children, HSE peaks between 3 months and 3 years of age, coinciding with the time of primary infection. In a subset of children, HSE results from a series of monogenic primary immunodeficiencies that impair UNC93B1- and TLR3 (603029)-dependent production of IFNA (147660)/IFNB (147640) and IFNG (147570) in the CNS (summary by Sancho-Shimizu et al., 2007). Genetic Heterogeneity of Susceptibility to Acute Infection-Induced Encephalopathy, including Herpes Simplex Encephalitis (HSE) For other forms of susceptibility to acute infection-induced encephalopathy, see herpes-specific IIAE2 (613002), caused by mutation in the TLR3 gene (603029) on chromosome 4q35; IIAE3 (608033), caused by mutation in the RANBP2 gene (601181) on chromosome 2q12; IIAE4 (614212), caused by mutation in the CPT2 gene (600650) on chromosome 1p32; herpes-specific IIAE5 (614849), caused by mutation in the TRAF3 gene (601896) on chromosome 14q32; herpes-specific IIAE6 (614850), caused by mutation in the TICAM1 gene (607601) on chromosome 19p13; herpes-specific IIAE7 (616532), caused by mutation in the IRF3 gene (603734) on chromosome 19q13; and herpes-specific IIAE8 (617900), caused by mutation in the TBK1 gene (604834) on chromosome 12q14.
Cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and mental retardation (summary by Gulsuner et al., 2011). For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (224050).
PTHSL1 is an autosomal recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, severe speech impairment or regression, and behavioral abnormalities. Most patients have onset of seizures within the first years of life. Some patients may have cortical dysplasia on brain imaging (summary by Smogavec et al., 2016).
Hutchinson-Gilford progeria syndrome is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected rate (failure to thrive). They develop a characteristic facial appearance including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears. Hutchinson-Gilford progeria syndrome also causes hair loss (alopecia), aged-looking skin, joint abnormalities, and a loss of fat under the skin (subcutaneous fat). This condition does not affect intellectual development or the development of motor skills such as sitting, standing, and walking.People with Hutchinson-Gilford progeria syndrome experience severe hardening of the arteries (arteriosclerosis) beginning in childhood. This condition greatly increases the chances of having a heart attack or stroke at a young age. These serious complications can worsen over time and are life-threatening for affected individuals.
Omodysplasia-2 is a rare autosomal dominant skeletal dysplasia characterized by shortened humeri, dislocated radial heads, shortened first metacarpals, craniofacial dysmorphism, and variable genitourinary anomalies (Saal et al., 2015). For a discussion of genetic heterogeneity of OMOD, see 258315.
Cap myopathy is a disorder that primarily affects skeletal muscles, which are muscles that the body uses for movement. People with cap myopathy have muscle weakness (myopathy) and poor muscle tone (hypotonia) throughout the body, but they are most severely affected in the muscles of the face, neck, and limbs. The muscle weakness, which begins at birth or during childhood, can worsen over time.Affected individuals may have feeding and swallowing difficulties in infancy. They typically have delayed development of motor skills such as sitting, crawling, standing, and walking. They may fall frequently, tire easily, and have difficulty running, climbing stairs, or jumping. In some cases, the muscles used for breathing are affected, and life-threatening breathing difficulties can occur.People with cap myopathy may have a high arch in the roof of the mouth (high-arched palate), severely drooping eyelids (ptosis), and a long face. Some affected individuals develop an abnormally curved lower back (lordosis) or a spine that curves to the side (scoliosis).The name cap myopathy comes from characteristic abnormal cap-like structures that can be seen in muscle cells when muscle tissue is viewed under a microscope. The severity of cap myopathy is related to the percentage of muscle cells that have these caps. Individuals in whom 70 to 75 percent of muscle cells have caps typically have severe breathing problems and may not survive childhood, while those in whom 10 to 30 percent of muscle cells have caps have milder symptoms and can live into adulthood.
The accumulation of excess triglyceride in the liver, a condition known as hepatic steatosis (or fatty liver), is associated with adverse metabolic consequences including insulin resistance and dyslipidemia. Factors promoting deposition of fat in the liver include obesity, diabetes, insulin resistance, and alcohol ingestion. Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease in Western countries. In a subset of individuals hepatic steatosis promotes an inflammatory response in the liver, referred to as steatohepatitis, which can progress to cirrhosis and liver cancer (summary by Romeo et al., 2008). Cohen et al. (2011) reviewed nonalcoholic fatty liver disease. Genetic Heterogeneity of Nonalcoholic Fatty Liver Disease Another form of nonalcoholic fatty liver disease (NAFLD2; 613387) has been associated with variation in the APOC3 gene (107720).
Fuchs endothelial dystrophy is a condition that causes vision problems. The first symptom of this condition is typically blurred vision in the morning that usually clears during the day. Over time, affected individuals lose the ability to see details (visual acuity). People with Fuchs endothelial dystrophy also become sensitive to bright lights.Fuchs endothelial dystrophy specifically affects the front surface of the eye called the cornea. Deposits called guttae, which are detectable during an eye exam, form in the middle of the cornea and eventually spread throughout the cornea. These guttae contribute to the ongoing cell death within the cornea, leading to worsening vision problems. Tiny blisters may develop on the cornea, which can burst and cause eye pain.The signs and symptoms of Fuchs endothelial dystrophy usually begin in a person's forties or fifties. A very rare early-onset variant of this condition starts to affect vision in a person's twenties.
Fuchs endothelial corneal dystrophy (FECD) is the most common genetic disorder of the corneal endothelium. Late-onset FECD is marked by thickening of Descemets membrane and excrescences, called guttae, that typically appear in the fourth or fifth decade. Disease progression results in decreased visual acuity as a result of increasing corneal edema, and end-stage disease is marked by painful epithelial bullae (summary by Riazuddin et al., 2013). For a discussion of genetic heterogeneity of Fuchs endothelial corneal dystrophy, see FECD1 (136800).
Fuchs endothelial corneal dystrophy (FECD) is the most common genetic disorder of the corneal endothelium. Late-onset FECD is marked by thickening of Descemets membrane and excrescences, called guttae, that typically appear in the fourth or fifth decade. Disease progression results in decreased visual acuity as a result of increasing corneal edema, and end-stage disease is marked by painful epithelial bullae (summary by Riazuddin et al., 2013). For a discussion of genetic heterogeneity of Fuchs corneal dystrophy, see FECD1 (136800).
Waardenburg syndrome type 4 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the eye, deafness, and Hirschsprung disease (review by Read and Newton, 1997). WS type 4C is caused by mutation in the SOX10 gene (602229). WS type 4 is genetically heterogeneous (see WS4A; 277580). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS2 (193510), and WS3 (148820).
Waardenburg syndrome type 4 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the eye, deafness, and Hirschsprung disease (review by Read and Newton, 1997). WS type 4B is caused by mutation in the EDN3 gene (131242). WS type 4 is genetically heterogeneous (see WS4A; 277580). For a description of other clinical variants of Waardenburg syndrome, see WS1 (193500), WS2 (193510), and WS3 (148820).
Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005). Dominant intermediate Charcot-Marie-Tooth disease E and focal segmental glomerulonephritis (CMTDIE; 614455) is also caused by heterozygous mutation in the INF2 gene. For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Factor XIII deficiency is an autosomal recessive hematologic disorder characterized by increased bleeding and poor wound healing. Most cases of congenital factor XIII deficiency result from mutation in the A subunit (Kangsadalampai et al., 1999). Ichinose et al. (1996, 2000) proposed a classification of factor XIII deficiency: XIIIA deficiency (formerly 'type II' F13 deficiency) and XIIIB deficiency (formerly 'type I' F13 deficiency), as well as a possible combined deficiency of the 2.
Nasopharyngeal carcinoma is a multifactorial malignancy associated with both genetic and environmental factors. The cancer arises from the epithelium of the nasopharynx (summary by Tse et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of susceptibility to nasopharyngeal carcinoma, see NPCA1 (607107).
Cleft lip or palate affecting the midline region of the palate.
Longevity, or extended life span, is a complex trait, determined by multiple genes as well as by environmental factors. Longevity has been associated with a locus on chromosome 4 (LGV1). Longevity has also been associated with a locus on chromosome 6q21 (LGV2; 606460). See also 502000 for a discussion of aging related to changes in mitochondrial DNA.
For a description and a discussion of genetic heterogeneity of fasting plasma glucose as a quantitative trait, see FGQTL1 (612108). FGQTL2 represents a locus associated with variation in fasting plasma glucose on chromosome 7p15-p13 in the vicinity of the glucokinase gene (GCK; 138079). Birth Weight as a Quantitative Trait Birth weight is a complex multifactorial trait. The extremes of birth weight are associated with high risks of perinatal morbidity and mortality. In addition, there are well-documented observational associations between lower birth weight and later-life chronic disease, including type 2 diabetes, cardiovascular disease, and higher blood pressure (e.g., Barker et al., 1993). Birth weight may be influenced directly by fetal genotype and indirectly by maternal genotype operating through the intrauterine environment. The importance of genetic factors acting independently of the intrauterine environment is illustrated by correlations between paternal height or weight and offspring birth weight, and genetic variants that are associated both with low birth weight and increased risk of type 2 diabetes may account for some of the observed correlation between these phenotypes (Hattersley and Tooke, 1999) (summary by Freathy et al., 2010). The BWQTL1 locus represents association of birth weight as a quantitative trait with single-nucleotide polymorphisms (SNPs) on chromosome 7p15-p13 in the vicinity of the glucokinase gene (GCK; 138079). The BWQTL2 locus (613459) represents association of birth weight with SNPs on chromosome 3q25. The BWQTL3 locus (613460) represents association of birth weight with SNPs on chromosome 3q21 in the vicinity of the ADCY5 gene (600293). The BWQTL4 locus (615192) represents association of birth weight with SNPs on chromosome 6p22.3 in the vicinity of the CDKAL1 gene (611259). For discussion of a possible association between birth weight and DLK1 levels, see 176290.
Congenital tufting enteropathy (CTE) is a rare inherited intractable diarrhea of infancy characterized by villous atrophy and absence of inflammation, with intestinal epithelial cell dysplasia manifesting as focal epithelial tufts in the duodenum and jejunum. CTE presents in the first few months of life with chronic watery diarrhea and failure to thrive, and most affected individuals require parenteral nutrition for normal growth and development (summary by Sivagnanam et al., 2008). Semiquantitative assessment of the epithelial surface in CTE patients revealed that 80 to 90% contained tufts, compared to only 16% in patients with celiac disease and less than 10% in normal jejunum (Reifen et al., 1994). For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
17p13.3 microduplication syndrome is characterized by variable psychomotor delay and dysmorphic features.
LMNA-related congenital muscular dystrophy (L-CMD) is a condition that primarily affects muscles used for movement (skeletal muscles). It is part of a group of genetic conditions called congenital muscular dystrophies, which cause weak muscle tone (hypotonia) and muscle wasting (atrophy) beginning very early in life.In people with L-CMD, muscle weakness becomes apparent in infancy or early childhood and can worsen quickly. The most severely affected infants develop few motor skills, and they are never able to hold up their heads, roll over, or sit. Less severely affected children may learn to sit, stand, and walk before muscle weakness becomes apparent. First the neck muscles weaken, causing the head to fall forward (dropped-head syndrome). As other skeletal muscles become weaker, these children may ultimately lose the ability to sit, stand, and walk unassisted.Other features of L-CMD often include spinal rigidity and abnormal curvature of the spine (scoliosis and lordosis); joint deformities (contractures) that restrict movement, particularly in the hips and legs; and an inward-turning foot. People with L-CMD also have an increased risk of heart rhythm abnormalities (arrhythmias).Over time, muscle weakness causes most infants and children with L-CMD to have trouble eating and breathing. The breathing problems result from restrictive respiratory insufficiency, which occurs when muscles in the chest are weakened and the ribcage becomes increasingly rigid. This problem can be life-threatening, and many affected children require support with a machine to help them breathe (mechanical ventilation).
Weill-Marchesani syndrome is a rare connective tissue disorder characterized by microspherophakia, severe myopia, acute and/or chronic glaucoma, and cataract. Other features include brachydactyly and short stature. Patients may also have stiff joints and thickened skin, especially on the hands. Occasionally, cardiac defects or an abnormal heart rhythm is present (summary by Shah et al., 2014). For a discussion of genetic heterogeneity of Weill-Marchesani syndrome, see WMS1 (277600).
LTBP4-related cutis laxa is characterized by cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonary artery stenosis, and other evidence of a generalized connective disorder such as inguinal hernias and hollow visceral diverticula (e.g., intestine, bladder). Other manifestations can include diaphragmatic hernia, congenital heart disease, intestinal malrotation, and ectopic kidneys. Of the 17 affected individuals (from 13 families) reported to date, cutis laxa was evident from birth in most and pulmonary emphysema was present in all. Pulmonary emphysema is clinically evident during the first months of life, is often severe, and is the most common cause of death. Bladder diverticula and hydronephrosis are common.
Dystransthyretinemic hyperthyroxinemia is characterized by an increased affinity for thyroxine (T4) by transthyretin in clinically euthyroid individuals (summary by Moses et al., 1990).
Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, ependymomas, and subependymomas. Glial cells can show various degrees of differentiation even within the same tumor (summary by Kyritsis et al., 2010). Ependymomas are rare glial tumors of the brain and spinal cord (Yokota et al., 2003). Subependymomas are unusual tumors believed to arise from the bipotential subependymal cell, which normally differentiates into either ependymal cells or astrocytes. They were characterized as a distinct entity by Scheinker (1945). They tend to be slow-growing, noninvasive, and located in the ventricular system, septum pellucidum, cerebral aqueduct, or proximal spinal cord (summary by Ryken et al., 1994). Gliomas are known to occur in association with several other well-defined hereditary tumor syndromes such as mismatch repair cancer syndrome (276300), melanoma-astrocytoma syndrome (155755), neurofibromatosis-1 (NF1; 162200) and NF2 (101000), and tuberous sclerosis (TSC1; 191100). Familial clustering of gliomas may occur in the absence of these tumor syndromes, however. Genetic Heterogeneity of Susceptibility to Glioma Other glioma susceptibilities include GLM2 (613028), caused by variation in the PTEN gene (601728) on chromosome 10q23; GLM3 (613029), caused by variation in the BRCA2 gene (600185) on chromosome 13q12; GLM4 (607248), mapped to chromosome 15q23-q26.3; GLM5 (613030), mapped to chromosome 9p21; GLM6 (613031), mapped to chromosome 20q13; GLM7 (613032), mapped to chromosome 8q24; GLM8 (613033), mapped to chromosome 5p15; and GLM9, caused by variation in the POT1 gene (606478) on chromosome 7q31. Somatic mutation, disruption, or copy number variation of the following genes or loci may also contribute to the formation of glioma: ERBB (EGFR; 131550), ERBB2 (164870), LGI1 (604619), GAS41 (602116), GLI (165220), DMBT1 (601969), IDH1 (147700), IDH2 (147650), BRAF (164757), PARK2 (602544), TP53 (191170), RB1 (614041), PIK3CA (171834), 10p15, 19q, and 17p13.3.
For a general phenotypic description and a discussion of genetic heterogeneity of idiopathic generalized epilepsy, see 600669. Juvenile myoclonic epilepsy is a subtype of idiopathic generalized epilepsy; see 254770 for a general phenotypic description and a discussion of genetic heterogeneity of JME.
Both juvenile myoclonic epilepsy and juvenile absence epilepsy are subtypes of idiopathic generalized epilepsy (EIG). For a general phenotypic description and a discussion of genetic heterogeneity of these disorders, see EIG (600669), EJM (254770), and EJA (607631).
A reduction in the number of nerve cells in the basal ganglia.
Focal proliferation of glial cells in the basal ganglia. [HPO:probinson]
MDDGB4 is a rare autosomal recessive congenital muscular dystrophy that is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies.' In contrast to most dystroglycanopathies, mental retardation is not a feature of MDDGB4 (Godfrey et al., 2007). For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
SLC6A3-related dopamine transporter deficiency syndrome (DTDS) is a complex movement disorder with a continuum that ranges from classic early-onset DTDS (in the first 6 months) to atypical later-onset DTDS (in childhood, adolescence, or adulthood). Classic DTDS. Infants typically manifest nonspecific findings (irritability, feeding difficulties, axial hypotonia, and/or delayed motor development) followed by a hyperkinetic movement disorder (with features of chorea, dystonia, ballismus, orolingual dyskinesia). Over time, affected individuals develop parkinsonism-dystonia characterized by bradykinesia (progressing to akinesia), dystonic posturing, distal tremor, rigidity, and reduced facial expression. Limitation of voluntary movements leads to severe motor delay. Episodic status dystonicus, exacerbations of dystonia, and secondary orthopedic, gastrointestinal, and respiratory complications are common. Many affected individuals appear to show relative preservation of intellect with good cognitive development. Atypical DTDS. Normal psychomotor development in infancy and early childhood is followed by later-onset manifestations of parkinsonism-dystonia with tremor, progressive bradykinesia, variable tone, and dystonic posturing. The long-term outcome of this form is currently unknown.
Congenital fibrosis of the extraocular muscles is a disorder that affects the muscles that surround the eyes. These muscles control eye movement and the position of the eyes (for example, looking straight ahead). Congenital fibrosis of the extraocular muscles prevents the normal development and function of these muscles. As a result, affected individuals are unable to move their eyes normally. Most people with this condition have difficulty looking upward, and their side-to-side eye movement may also be limited. The eyes may be misaligned such that they look in different directions (strabismus). Instead of moving their eyes, affected individuals may need to turn their head to track moving objects. Additionally, many people with congenital fibrosis of the extraocular muscles have droopy eyelids (ptosis), which further limits their vision.Researchers have identified at least four forms of congenital fibrosis of the extraocular muscles, designated CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome. The specific problems with eye movement vary among the types. Tukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities in addition to problems with eye movement.
Central areolar choroidal dystrophy (CACD) is a hereditary retinal disorder that principally affects the macula, often resulting in a well-defined area of atrophy of the retinal pigment epithelium (RPE) and choriocapillaris in the center of the macula. Dysfunction of macular photoreceptors usually leads to a decrease in visual acuity, generally occurring between the ages of 30 and 60 years (summary by Boon et al., 2009). For a discussion of genetic heterogeneity of central areolar choroidal dystrophy, see CACD1 (215500).
A very rare inherited hair loss disorder with characteristics of sparse, fragile or absent hair on the scalp, eyebrows, eyelashes, axilla and rest of the body, associated with vesicle formation on various parts of the scalp and body which regularly burst and release watery fluid. Evidence suggests this syndrome is caused by homozygous mutation in the desmocollin-3 gene on chromosome 18q12.
Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset multisystem disorder characterized by bilateral renal cysts, liver cysts, and an increased risk of intracranial aneurysms. Other manifestations include: cysts in the pancreas, seminal vesicles, and arachnoid membrane; dilatation of the aortic root and dissection of the thoracic aorta; mitral valve prolapse; and abdominal wall hernias. Renal manifestations include hypertension, renal pain, and renal insufficiency. Approximately 50% of individuals with ADPKD have end-stage renal disease (ESRD) by age 60 years. The prevalence of liver cysts increases with age and occasionally results in clinically significant severe polycystic liver disease (PLD). Overall the prevalence of intracranial aneurysms is fivefold higher than in the general population and further increased in those with a positive family history of aneurysms or subarachnoid hemorrhage. There is substantial variability in the severity of renal disease and other extrarenal manifestations even within the same family.
Achromatopsia is a condition characterized by a partial or total absence of color vision. People with complete achromatopsia cannot perceive any colors; they see only black, white, and shades of gray. Incomplete achromatopsia is a milder form of the condition that allows some color discrimination.Achromatopsia also involves other problems with vision, including an increased sensitivity to light and glare (photophobia), involuntary back-and-forth eye movements (nystagmus), and significantly reduced sharpness of vision (low visual acuity). Affected individuals can also have farsightedness (hyperopia) or, less commonly, nearsightedness (myopia). These vision problems develop in the first few months of life.Achromatopsia is different from the more common forms of color vision deficiency (also called color blindness), in which people can perceive color but have difficulty distinguishing between certain colors, such as red and green.
Autosomal dominant tubulointerstitial kidney disease, REN-related (ADTKD-REN) (previously familial juvenile hyperuricemic nephropathy type 2 [FJHN2]) is characterized by: hypoproliferative anemia with low hemoglobin concentrations, found in most affected children by age one year; hyperuricemia and gout, found in most (not all) affected individuals; and slowly progressive chronic tubulointerstitial kidney disease. Some affected children have polyuria (excessive urine production leading to frequent urination) and enuresis. Mildly elevated serum creatinine concentration and reduced estimated glomerular filtration rate in an asymptomatic child often progresses to end-stage renal disease in the fourth to sixth decades of life. Of note, information on only 14 families with this condition has been published; better understanding of the disease is likely to emerge when more families are described.
A syndrome consisting of capillary malformation of the lower lip (C), lymphatic malformation of the face and neck (L), asymmetry of face and limbs (A) and partial or generalised overgrowth (O). It has been described in six unrelated patients. Capillary malformation of the lower lip is observed in all patients. The overgrowth was noted at birth in three patients but was generalised in only one patient; it was partial in the other patients and involved one or more body segments. Inheritance of this association is not known.
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterised by growth retardation, short stature, developmental delay, intellectual disability, craniofacial dysmorphism (severe microcephaly, sloping forehead, prominent eyes, broad nasal ridge, hypoplastic nasal septum, epicanthal folds), spontaneous chromosomal instability, cellular hypersensitivity to ionising radiation and radioresistant DNA synthesis, without severe infections, immunodeficiency or cancer predisposition. Additional reported features include mild spasticity, slight and nonprogressive ataxia, hyperopia, multiple pigmented nevi, widely spaced nipples, and clinodactyly.
A very rare inherited connective tissue disorder with characteristics of macrocephaly, sparse scalp hair, soft redundant and hyperextensible skin, joint hypermobility, and scoliosis. Patients have progressive facial coarsening with downslanted palpebral fissures, upper eyelid fullness/infraorbital folds, thick/everted vermillion, gingival overgrowth and abnormal position of the teeth. Rare manifestations such as abnormal high-pitched voice, bronchiectasis, hypergonadotropic hypergonadism and brachydactyly have also been reported. Caused by homozygous mutation in the RIN2 gene on chromosome 20p11.
Chronic mucocutaneous candidiasis (CMC) includes a group of rare disorders with altered immune responses, selective against Candida, characterized by persistent and/or recurrent infections of the skin, nails, and mucous membranes, caused by organisms of the genus Candida, mainly Candida albicans (Zuccarello et al., 2002). Isolated familial chronic mucocutaneous candidiasis is distinct from candidiasis with endocrinopathy (240300). In myeloperoxidase deficiency (254600), susceptibility to candidiasis may be increased. Genetic Heterogeneity of Candidiasis Familial candidiasis-1 (CANDF1) maps to chromosome 2p. CANDF2 (212050) is caused by mutation in the CARD9 gene (607212) on chromosome 9q34.3. CANDF3 (607644), a form restricted to nails of the hands and feet, maps to chromosome 11. CANDF4 (613108) is caused by mutation in the CLEC7A gene (606264) on chromosome 12p13. CANDF6 (613956) is caused by mutation in the IL17F gene (606496) on chromosome 6p12. CANDF7 (614162) is caused by mutation in the STAT1 gene (600555) on chromosome 2q32. CANDF8 (615527) is caused by mutation in the TRAF3IP2 gene (607043) on chromosome 6q21. CANDF9 (616445) is caused by mutation in the IL17RC gene (610925) on chromosome 3p25. A form of familial candidiasis, previously thought to be isolated and designated CANDF5, has been found to be part of a primary immune deficiency (IMD51; 613953) that includes Staphylococcal skin infections and increased susceptibility to chronic bacterial respiratory infections.
Camptodactyly is defined as a permanent flexion contrature of 1 or both fifth fingers at the proximal interphalangeal joints. Additional fingers might be affected, but the little finger is always involved. Usually the condition appears to be sporadic in a family, but clinical examination of relatives reveals that it is an autosomal dominant condition subject to incomplete penetrance and variable expressivity (summary by Malik et al., 2008).
Hereditary transthyretin (ATTR) amyloidosis is characterized by a slowly progressive peripheral sensorimotor and/or autonomic neuropathy as well as non-neuropathic changes of cardiomyopathy, nephropathy, vitreous opacities, and CNS amyloidosis. The disease usually begins in the third to fifth decade in persons from endemic foci in Portugal and Japan; onset is later in persons from other areas. Typically, sensory neuropathy starts in the lower extremities with paresthesias and hypesthesias of the feet, followed within a few years by motor neuropathy. In some persons, particularly those with early-onset disease, autonomic neuropathy is the first manifestation of the condition; findings can include: orthostatic hypotension, constipation alternating with diarrhea, attacks of nausea and vomiting, delayed gastric emptying, sexual impotence, anhidrosis, and urinary retention or incontinence. Cardiac amyloidosis is mainly characterized by progressive cardiomyopathy. Individuals with leptomeningeal amyloidosis may have the following CNS findings: dementia, psychosis, visual impairment, headache, seizures, motor paresis, ataxia, myelopathy, hydrocephalus, or intracranial hemorrhage.
Mitochondrial HMG-CoA synthase deficiency is an inherited metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting (summary by Aledo et al., 2006).
Platelet prostaglandin-endoperoxidase synthase-1 deficiency is a hematologic disorder characterized by mildly increased bleeding due to a platelet defect. The PTGS1 gene (176805) encodes prostaglandin-endoperoxidase synthase-1, also known as COX1 or PGHS1, which catalyzes the formation of prostaglandin G2 (PGG2) and prostaglandin H2 from arachidonic acid, and the downstream formation of thromboxane A2 (TXA2) and prostacyclin. Thromboxane A2 is important for platelet aggregation (summary by Matijevic-Aleksic et al., 1996).
Cerebral amyloid angiopathy, or cerebroarterial amyloidosis, refers to a pathologic process in which amyloid protein progressively deposits in cerebral blood vessel walls with subsequent degenerative vascular changes that usually result in spontaneous cerebral hemorrhage, ischemic lesions, and progressive dementia. APP-related CAA is the most common form of CAA (Revesz et al., 2003, 2009).
Cutaneous basal cell carcinoma (BCC) is the most common cancer among people of European ancestry (Stacey et al., 2009). The primary environmental risk factor for BCC is sun exposure, but genetics also has a substantial role. Some of the sequence variants that confer susceptibility seem to operate through their association with fair-pigmentation traits common among Europeans, resulting in reduced protection from the damaging effects of ultraviolet (UV) radiation. Other sequence variants have no obvious role in pigmentation or UV susceptibility but instead seem to operate in the contexts of growth and differentiation of the basal layers of the skin (Stacey et al., 2008; Epstein, 2008; Gudbjartsson et al., 2008; Rafnar et al., 2009). See ASIP (600201), TYR (606933), and SHEP5 (227240) for examples of basal cell carcinoma associated with fair skin or sensitivity to sun. Basal cell carcinoma occurs as a feature of multiple syndromes, including basal cell nevus syndrome (BCNS; 109400), Bazex syndrome (301845), Rombo syndrome (180730), Brooke-Spiegler syndrome (605041), Muir-Torre syndrome (158320), and xeroderma pigmentosum (see 278700). Abnormalities in the Hedgehog signaling pathway are found in basal cell carcinomas; see SHH (600725) and SMOH (601500). Genetic Heterogeneity of Susceptibility to Basal Cell Carcinoma Susceptibility to basal cell carcinoma is a genetically heterogeneous trait. The BCC1 locus maps to chromosome 1p36. Also see BCC2 (613058) on 1q42; BCC3 (613059) on 5p15; BCC4 (613061) on 12q13; BCC5 (613062)on 9p21; and BCC6 (613063)on 7q32. Variation in the 3-prime untranslated region of TP53 (191170) increases susceptibility to basal cell carcinoma (BCC7; 614740). Somatic mutation contributing to the formation of basal cell carcinoma has been identified in the RASA1 (139150), PTCH1 (601309), and PTCH2 (603673) genes.
This is an autosomal recessive disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy, and leukodystrophy. Recognition and diagnosis of this disorder is critical because folinic acid therapy can reverse the clinical symptoms and improve brain abnormalities and function (Steinfeld et al., 2009).
Idiopathic generalized epilepsy (EIG) is a broad term that encompasses several common seizure phenotypes, classically including childhood absence epilepsy (CAE, ECA), juvenile absence epilepsy (JAE), and juvenile myoclonic epilepsy (JME, EJM) (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). Generalized epilepsy with febrile seizures plus (GEFS+) shows phenotypic overlap with IGE, and includes patients with early-onset febrile seizures who later develop various types of febrile and afebrile seizures, such as those observed in EIG (summary by Singh et al., 1999). For a general phenotypic description and a discussion of genetic heterogeneity of EIG, see 600669. For a general phenotypic description and a discussion of genetic heterogeneity of GEFS+, see 604233. For a general phenotypic description and a discussion of genetic heterogeneity of EJM, see 254770.
Combined pituitary hormone deficiency (CPHD) in man denotes impaired production of growth hormone (GH; 139250) and one or more of the other 5 anterior pituitary hormones. Mutations of the POU1F1 gene in the human and Pit1 in the mouse are responsible for pleiotropic deficiencies of GH, prolactin (PRL; 176760), and thyroid-stimulating hormone (TSH; see 188540), while the production of adrenocorticotrophic hormone (ACTH; see 176830), luteinizing hormone (LH; 152780), and follicle-stimulating hormone (FSH; 136530) are preserved (Wu et al., 1998). In infancy severe growth deficiency from birth as well as distinctive facial features with prominent forehead, marked midfacial hypoplasia with depressed nasal bridge, deep-set eyes, and a short nose with anteverted nostrils and hypoplastic pituitary gland by MRI examination can be seen (Aarskog et al., 1997). Some cases present with severe mental retardation along with short stature (Radovick et al., 1992). Genetic Heterogeneity of Combined Pituitary Hormone Deficiency CPHD2 (262600), associated with hypogonadism, is caused by mutation in the PROP1 gene (601538). CPHD3 (221750), which is associated with rigid cervical spine and variable sensorineural deafness, is caused by mutation in the LHX3 gene (600577). CPHD4 (262700) is caused by mutation in the LHX4 gene (602146). CPHD5 (see septooptic dysplasia, 182230) is caused by mutation in the HESX1 gene (601802). CPHD6 (613986) is caused by mutation in the OTX2 gene (600037).
Regular exposure to continuous noise or an exposure to a single acoustic overstimulation can lead to noise-induced hearing loss (NIHL). Millions of people worldwide are exposed daily to harmful levels of noise, making NIHL a likely widespread occupational health hazard. NIHL is a complex disease resulting from an interaction between genetic and environmental factors and is highly variable between individuals (Konings et al., 2009).
The 19q13.11 microdeletion is characterized by several major features including pre and postnatal growth retardation, slender habitus, severe postnatal feeding difficulties, microcephaly, intellectual deficit with speech disturbance, hypospadias and ectodermal dysplasia presented by scalp aplasia, thin and sparse hair, eyebrows and eyelashes, thin and dry skin and dysplasic nails.
Follicular non-Hodgkin lymphoma is an indolent B-cell malignancy with an annual incidence exceeding 10,000 cases in the United States (Bohen et al., 2003). One form of susceptibility to follicular lymphoma (FL1) is associated with a region on chromosome 6p21.33.
Neuroblastoma is a type of cancer that most often affects children. Neuroblastoma occurs when immature nerve cells called neuroblasts become abnormal and multiply uncontrollably to form a tumor. Most commonly, the tumor originates in the nerve tissue of the adrenal gland located above each kidney. Other common sites for tumors to form include the nerve tissue in the abdomen, chest, neck, or pelvis. Neuroblastoma can spread (metastasize) to other parts of the body such as the bones, liver, or skin.Individuals with neuroblastoma may develop general signs and symptoms such as irritability, fever, tiredness (fatigue), pain, loss of appetite, weight loss, or diarrhea. More specific signs and symptoms depend on the location of the tumor and where it has spread. A tumor in the abdomen can cause abdominal swelling. A tumor in the chest may lead to difficulty breathing. A tumor in the neck can cause nerve damage known as Horner syndrome, which leads to drooping eyelids, small pupils, decreased sweating, and red skin. Tumor metastasis to the bone can cause bone pain, bruises, pale skin, or dark circles around the eyes. Tumors in the backbone can press on the spinal cord and cause weakness, numbness, or paralysis in the arms or legs. A rash of bluish or purplish bumps that look like blueberries indicates that the neuroblastoma has spread to the skin.In addition, neuroblastoma tumors can release hormones that may cause other signs and symptoms such as high blood pressure, rapid heartbeat, flushing of the skin, and sweating. In rare instances, individuals with neuroblastoma may develop opsoclonus myoclonus syndrome, which causes rapid eye movements and jerky muscle motions. This condition occurs when the immune system malfunctions and attacks nerve tissue.Neuroblastoma occurs most often in children before age 5 and rarely occurs in adults.
Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that usually affects middle-aged women and eventually leads to liver failure (summary by Kaplan, 1996). For a discussion of genetic heterogeneity of primary biliary cirrhosis (PBC), see PBC1 (109720).
Herpes simplex encephalitis (HSE) is a severe viral infection of the central nervous system (CNS) resulting most commonly from infection with HSV-1 and occasionally by HSV-2. The disease peaks in childhood between 3 months and 3 years of age, although later onset can also occur, and affected individuals usually have neurologic sequelae, including seizures and cognitive or motor impairment. Some individuals may have recurrences of an acute episode of HSE; however, patients have no clear susceptibility to infection to other viruses. The virus gains entry to the CNS through a neuronal route via the trigeminal or olfactory nerves, not via the blood. Replication of this enveloped double-stranded DNA (dsDNA) virus involves the production and accumulation of RNA species, including dsRNA, which are recognized by the intracellular TLR3 signaling pathway. The susceptibility to HSV in particular appears to result from impaired TLR3-dependent interferon production by nonhematopoietic cells that reside within the CNS (review by Zhang et al., 2013; summary by Mork et al., 2015). For a general phenotypic description of herpes simplex encephalitis and a discussion of genetic heterogeneity of acute infection-induced encephalopathy, see 610551.
Age-related hearing impairment (ARHI), or presbycusis, is the progressive, bilaterally symmetric deterioration of hearing ability that occurs with aging. Studies of the cochlea in many animal species and of the histopathology of human temporal bones have shown that stria vascularis volumes and spiral ganglion cell, inner hair cell, and outer hair cell populations, as well as many other cochlear cell types and structures, undergo age-related degeneration. Environmental risk factors for ARHI include noise exposure, smoking, ototoxic medication, and cardiovascular disease. Heritability estimates vary between 0.25 and 0.75 depending on, among other factors, study design (family vs twins), age range of the study population, and the phenotype studied (Huyghe et al., 2008).
Mutations in the FOXE3 gene have been found to cause multiple types of cataract, which have been described as membranous and posterior subcapsular.
Congenital conditions in individuals with a male karyotype, in which the development of the gonadal or anatomical sex is atypical.
Myofibrillar myopathy-6 is an autosomal dominant severe neuromuscular disorder characterized by onset in the first decade of rapidly progressive generalized and proximal muscle weakness, respiratory insufficiency, cardiomyopathy, and skeletal deformities related to muscle weakness. Muscle biopsy shows fiber-type grouping, disruption of the Z lines, and filamentous inclusions, and sural nerve biopsy shows a neuropathy, often with giant axonal neurons. Most patients are severely affected by the second decade and need cardiac transplant, ventilation, and/or a wheelchair (summary by Jaffer et al., 2012). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy (MFM), see MFM1 (601419).
RNAse T2-deficient leukoencephalopathy is a disorder that affects the brain. People with RNAse T2-deficient leukoencephalopathy have neurological problems that become apparent during infancy; the problems generally do not worsen over time (progress). Most affected individuals have severe intellectual disability; muscle stiffness (spasticity); and a delay in developing motor skills such as sitting, crawling, and walking. Some do not learn to walk, and most do not develop the ability to speak. Other neurological features that can occur in RNAse T2-deficient leukoencephalopathy include hearing loss caused by abnormalities in the inner ear (sensorineural deafness), seizures, involuntary writhing movements of the hands (athetosis), uncontrolled muscle tensing (dystonia), and involuntary eye movements (nystagmus). In addition to the neurological problems associated with this disorder, some affected individuals have unusual facial features sometimes described as a ""doll-like face.""The neurological problems in this disorder are caused by abnormalities in the brain. People with this condition have leukoencephalopathy, an abnormality of the brain's white matter that can be detected with medical imaging. White matter consists of nerve fibers covered by a fatty substance called myelin. Myelin insulates nerve fibers and promotes the rapid transmission of nerve impulses. In people with RNAse T2-deficient leukoencephalopathy, myelin is not made in sufficient amounts during development, leading to patchy white matter abnormalities (lesions) in the brain. In addition, individuals with RNAse T2-deficient leukoencephalopathy may have cysts in regions of the brain called the temporal lobes and enlargement of the fluid-filled cavities (ventricles) near the center of the brain. The white matter lesions are primarily concentrated around the cysts and the ventricles. An abnormally small head and brain size (microcephaly) often occurs in this disorder.
An abnormal accumulation of fluid beneath the skin on the back of the hands.
A rare syndrome with characteristics of onset growth retardation (low birth weight and short stature), hypotonia, developmental delay and intellectual disability associated with microcephaly and craniofacial (low anterior hairline, hypotelorism, thick lips with carp-shaped mouth, high-arched palate, low-set ears), cardiac (conotruncal heart malformations such as tetralogy of Fallot and skeletal (hypoplastic thumbs and first metacarpals) abnormalities.
Ventricular fibrillation (VF) is said to cause more than 300,000 sudden deaths each year in the US alone. In approximately 5 to 12% of cases, there are no demonstrable cardiac or noncardiac causes to account for the episode, which is therefore classified as idiopathic ventricular fibrillation (IVF). Patients with a distinct form of VF called Brugada syndrome (see 601144) present with a characteristic electrocardiographic pattern, with right bundle branch block (RBBB) and elevation of ST segment in leads V1 to V3 and may account for 40 to 60% of all IVF cases (review by Chen et al., 1998). Mutations in the SCN5A gene were identified in patients with Brugada syndrome-1 (601144). Genetic Heterogeneity of Paroxysmal Familial Ventricular Fibrillation Another familial form of VF (VF2; 612956) is caused by mutation in the DPP6 gene (126141) on chromosome 7q26.
Cerebral palsy (CP) is defined as a nonprogressive but not unchanging disorder of posture or movement, caused by an abnormality of the brain and first evident at the stage of rapid brain development (Hughes and Newton, 1992). The most common forms result from factors surrounding difficulties before or at birth, such as severe perinatal asphyxia, congenital infection, prematurity, and multiple pregnancy (Blair and Stanley, 1988; Stanley, 1994). More rarely, familial clustering or absence of pre- or postpartum events indicate that there are genetic forms of the disorder (Lynex et al., 2004). Cerebral palsy can be classified according to the type of movement disorder: spastic cerebral palsy accounts for approximately 60% of cases and can be subdivided into hemiplegic, diplegic, quadriplegic, and monoplegic types, whereas other forms include athetoid/dyskinetic, ataxic (605388), and mixed (Gustavson et al., 1969). Genetic Heterogeneity of Spastic Quadriplegic Cerebral Palsy See also CPSQ2 (612900), caused by deletion of the ANKRD15 gene (KANK1; 607704) inherited on the paternal allele, and CPSQ3 (617008), caused by mutation in the ADD3 gene (601568) on 10q24. Related phenotypes that were formerly classified in the CPSQ series include spastic paraplegia-47 (SPG47; 614066), spastic paraplegia-50 (SPG50; 612936), spastic paraplegia-51 (SPG51; 613744), and spastic paraplegia-52 (614067).
The phenotype of autosomal recessive cutis laxa type II (ARCL2) includes cutis laxa of variable severity, abnormal growth, developmental delay, and associated skeletal abnormalities (summary by Morava et al., 2009). No specific clinical features distinguish ARCL2A (219200), which includes a glycosylation defect, and ARCL2B, in which abnormal glycosylation has not been reported (Morava et al., 2009; Guernsey et al., 2009). For a phenotypic description and discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100).
Growth retardation, developmental delay, and facial dysmorphism (GDFD) is an autosomal recessive multiple congenital anomaly syndrome characterized by severe psychomotor retardation, poor overall growth, and dysmorphic facial features. Additional features may include cardiac malformations and deafness (summary by Daoud et al., 2016).
AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a group of neurodegenerative disorders characterized by a progressive, complex spastic paraplegia with onset typically in infancy or early childhood. Early-onset hypotonia evolves into progressive lower-extremity spasticity. The majority of children become non-ambulatory and usually wheelchair bound. Over time spasticity progresses to involve the upper extremities, resulting in a spastic tetraplegia. Associated complications include dysphagia, contractures, foot deformities, dysregulation of bladder and bowel function, and a pseudobulbar affect. About 50% of affected individuals have seizures. Postnatal microcephaly (usually in the -2SD to -3SD range) is common. All have global developmental delay. Speech development is significantly impaired and many affected individuals remain nonverbal. Intellectual disability in older children is usually moderate to severe.
Congenital disorder of glycosylation type It (CDG1T) is an autosomal recessive disorder characterized by a wide range of clinical manifestations and severity. The most common features include cleft lip and bifid uvula, apparent at birth, followed by hepatopathy, intermittent hypoglycemia, short stature, and exercise intolerance, often accompanied by increased serum creatine kinase. Less common features include rhabdomyolysis, dilated cardiomyopathy, and hypogonadotropic hypogonadism (summary by Tegtmeyer et al., 2014). For a discussion of the classification of CDGs, see CDG1A (212065).
Complete deficiency of erythrocyte AMP deaminase is a clinically benign disorder (Ogasawara et al., 1987; Zydowo et al., 1989).
A very rare tricarboxylic acid cycle disorder resulting from a deficiency in alpha-ketoglutarate dehydrogenase (one of the three subunits of the alpha-ketoglutarate dehydrogenase complex), that most often presents in the neonatal period with hypotonia, severe encephalopathy, extrapyramidal signs, pyramidal tract dysfunction and seizures and that frequently results in death in early childhood. Metabolic acidosis, elevated lactate and glutamate levels and variable degrees of glutaric aciduria are noted. Sudden death, myocardiopathy, and hepatic disorders have also been reported in some cases.
Alpha-2-plasmin inhibitor deficiency is a rare autosomal recessive hemorrhagic diathesis. Most bleeds are severe, appear during childhood, and, in a few cases, umbilical bleeding is the first manifestation. Some homozygous patients present only moderate bleeding (Favier et al., 2001).
Female pelvic floor disorders, including pelvic organ prolapse (POP), urinary incontinence, and stress urinary incontinence, affect over one-third of adult women (Bump and Norton, 1998). These disorders are characterized by weakening of the tissues supporting and anchoring the pelvic organs, which can affect both structure and function of the vagina, uterus, bladder, anus, and intestines.
Malpositioning, or ectopic placement, of teeth is believed to result from a disturbance of the tooth developmental structure. Various forms of the disorder tend to be associated with one another and with hypodontia. It is important to recognize any associations of tooth anomalies as early diagnosis of developmental disturbance in a single tooth may reveal a potential risk of future position or eruption disturbances of other teeth and thus allow early intervention (Bjerklin et al., 1992).
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that are activated by fatty acids and their derivatives. PPAR has three subtypes (PPARalpha, beta/delta, and gamma) showing different expression patterns in vertebrates. Each of them is encoded in a separate gene and binds fatty acids and eicosanoids. PPARalpha plays a role in the clearance of circulating or cellular lipids via the regulation of gene expression involved in lipid metabolism in liver and skeletal muscle. PPARbeta/delta is involved in lipid oxidation and cell proliferation. PPARgamma promotes adipocyte differentiation to enhance blood glucose uptake.
The process of removing one or more methyl groups from a molecule, involving the oxidation (i.e. electron loss) of one or more atoms in the substrate. [GOC:BHF, GOC:mah, GOC:rl]
A species of smut fungi in the phylum Basidiomycota. This species causes loose smut of barley.
The root of the plant Glycyrrhiza glabra with potential anti-inflammatory, antioxidant and antineoplastic activities. Licorice root contains the calcium and potassium salts of the glycoside glycerrhizinic acid (also known as glycyrrhizin) and numerous flavonoids. After hydrolysis from glycerrhizinic acid in vivo, glycyrrhetinic acid (GA) inhibits 11 beta-hydroxysteroid dehydrogenase, resulting in inhibition of the conversion of cortisol to the inactive steroid cortisone, elevated cortisol levels, and increased binding of cortisol to mineralocorticoid receptors. In addition, GA inhibits 17,20-lyase and 17 beta-hydroxysteroid dehydrogenase, resulting in decreased conversions of 17-hydroxyprogesterone to androstenedione and androstenedione to testosterone. The primary antioxidant found in licorice root, the flavonoid glabridin, has been shown to inactivate or inhibit the activities of some human P450 enzymes in vitro. In some tumor cells, beta-hydroxy-DHP, another flavonoid found in licorice root, may induce Bcl-2 phosphorylation, apoptosis, and G2/M cell cycle arrest; this mechanism of action is similar to that of the antimicrotubule agents. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=471833&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=471833&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61436"" NCI Thesaurus)
A social or emotional detachment, pathological retreat from objective reality, interpersonal contact and social involvement, as in some forms of schizophrenia, depression, or schizoid, avoidant, or schizotypal personality disorders.
The return of a sign, symptom, or disease after a remission.
An acute myeloid leukemia with inv(16)(p13.1q22) occurring in adults.
A term referring to acute myeloid leukemias with rearrangement of the MLL gene which results in translocations with various genes other than the MLLT3 (AF9) gene.
A term referring to acute myeloid leukemias which show variant translocations involving the RARA gene. The variant fusion partners include NUMA1, ZBTB16, STAT5B, and NPM1. These leukemias often have the morphologic features of acute promyelocytic leukemia.
Acute myeloid leukemia with the variant RARA t(11;17)(q23;q21) and the expression of PLZF-RARA fusion protein. It lacks differentiation response to retinoids treatment.
Acute myeloid leukemia with the variant RARA t(11;17)(q13;q21) and the expression of NUMA1-RARA fusion protein.
An acute myeloid leukemia with at least 20% blasts in the bone marrow or blood, and either a previous history of myelodysplastic syndrome, multilineage dysplasia or myelodysplastic syndrome-related cytogenetic abnormalities. There is no history of prior cytotoxic therapy for an unrelated disorder, and there is absence of the cytogenetic abnormalities that are present in acute myeloid leukemia with recurrent genetic abnormalities.
An interpretation of results of an experiment.
The outcome of an experiment or set of experiments, including observations and primary, processed, and analyzed data.
Acute myeloid leukemia or myelodysplastic syndrome occurring in children with Down syndrome. The acute myeloid leukemia is usually an acute megakaryoblastic leukemia, and is associated with GATA1 gene mutation.
A cancer vaccine consisting of autologous, mature monocyte-derived dendritic cells (DCs) transfected with oncofetal antigen immature laminin receptor protein (OFA-iLRP) RNA, with potential antineoplastic activity. Upon administration, DCs in the OFA-iLRP RNA-transfected autologous dendritic cell vaccine express, process, and present OFA-iLRP to the host immune system, which may mount a potent cytotoxic T-cell (CTL) response against OFA-iLRP-expressing tumor cells. As a highly conserved protein, OFA-iLRP is preferentially expressed in fetal tissues and in many types of cancer, including hematopoietic malignancies, but is not detectable in normal differentiated adult cells.
Long-standing and persistent renal disease without kidney damage.
A first-degree relative (parent, sibling, child) documented to have died suddenly of presumed cardiac etiology without other obvious cause.
The number of coronary arteries that have at least 70% luminal obstruction.
A narrowing of the proximal portion of the left main coronary artery, usually considered significant if the stenosis is 70% or greater.
The coronary lesions treated during a PCI (Percutaneous Coronary Intervention) procedure.
The connection where the graft joins the coronary artery, usually less than or equal to 3 mm from insertion point.
Clinical diagnosis of heart failure during a hospitalization, of which heart failure was not the admitting diagnosis.
Clinical diagnosis of stroke during a hospitalization, of which stroke was not the admitting diagnosis.
Clinical diagnosis of angina during a hospitalization, of which angina was not the admitting diagnosis.
Clinical diagnosis of a repeated infarction of an organ during a hospitalization.
The description of an event that occurred in an individual during the hospitalization period.
A class of agents, other than statins, that are capable of inhibiting absorption of cholesterol, reducing the production and release of LDL from the liver, the release of free fatty acids stored in fat cells, or reducing the production of triglycerides.
An orally available liquid suspension containing the tropomyosin receptor kinase (Trk) inhibitor AZD6918 with potential antineoplastic activity. AZD6918 binds to Trk, thereby preventing neurotrophin-Trk interaction and Trk activation, and may eventually result in cell cycle arrest and apoptosis of tumor cells that express Trk. Trk, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.
The percentage of narrowing of the left main coronary artery.
The percentage narrowing of the proximal portion of the left main coronary artery.
Percent of the myocardial tissue estimated to exhibit characteristics of inadequate blood flow (ischemia). This is usually determined using a functional study (e.g. MRI, SPECT or PET).
Any substance, other than insulin, used to treat hyperglycemia.
A chloroethylamine derivative, with alkylating activity. Bofumustine alkylates DNA and forms DNA-DNA crosslinks, which result in the inhibition of DNA, RNA and protein synthesis and ultimately the induction of apoptosis.
The acetate salt form of sotrastaurin, an orally available pan-protein kinase C (PKC) inhibitor with potential immunosuppressive and antineoplastic activities. Sotrastaurin inhibits both T- and B-cell activations via PKC theta and beta isozymes, respectively. Both PKCs are important in the activation of nuclear factor-kappaB (NF-kB). Inhibition of PKC beta in B-cells results in prevention of NF-kB-mediated signaling and down regulation of NF-kB target genes. This may eventually lead to an induction of G1 cell cycle arrest and tumor cell apoptosis in susceptible tumor cells. This agent may act synergistically with other chemotherapeutic agents. PKC, a family of serine/threonine protein kinases overexpressed in certain types of cancer cells, is involved in cell differentiation, mitogenesis, inflammation, and the activation and survival of lymphocytes.
The mesylate salt form of dezaguanine, a purine nucleoside analogue with antineoplastic and antiviral activities. By competing with guanine, dezaguanine gets incorporated into DNA and inhibits DNA synthesis, thereby inducing cell death.
A leukemia arising as a result of the mutagenic effect of chemotherapy agents that are used for the treatment of a malignant tumor or exposure to ionizing radiation.
A long-acting derivative of sulfamezathine that is used in the poultry, swine and cattle industries for the treatment of coccidiosis and various bacterial infections.
IgA is the immunoglobulin subclass that is associated with antibody-mediated mucosal immunity. It is secreted as dimers into the mucosa and is the most effective isotype at fixing complement by the alternative pathway, even though it lacks the ability to fix complement by the classical pathway. There are two subtypes in the human - IgA1 and IgA2.
An agent belonging to the class of loop diuretics.
An immunophenotypic test result indicating positive staining of neoplastic cells for synaptophysin.
The sodium salt form of cefazaflur, a semisynthetic first-generation cephalosporin with antibacterial activity. Cefazaflur binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
The sodium salt form of cefpimizole, a semisynthetic, broad-spectrum, third-generation cephalosporin with antibacterial activity. Cefpimizole binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
The sulfate form of cefquinome, a semisynthetic, broad-spectrum, fourth-generation aminothiazolyl cephalosporin with antibacterial activity. Cefquinome binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
The anhydrous form of gadofosveset, an injectable, intravascular, amphiphilic gadolinium-based contrast agent (GBCA) used with magnetic resonance angiography (MRA) imaging. Gadofosveset is a stable gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) chelate derivative with a diphenylcyclohexylphosphate group. Upon injection, gadofosveset binds reversibly to endogenous serum albumin which increases its intravascular retention time compared to non-protein binding contrast agents. The serum albumin binding also increases T1-relaxivity of gadofosveset. This produces an increase in signal intensity of blood, thereby enhancing the visualization of blood vessels upon MRA and may aid in the diagnosis of certain blood vessels and heart disorders.
A hydrazide derivative of m-sulfamoylbenzoic acid with diuretic activity. Alipamide primarily causes a saluretic effect and is able to inhibit carbonic anhydrase at higher doses which may also contribute to this agent's diuretic effect.
An ethacrynic acid derivative with diuretic activity.
The tartrate salt form of metyrapone, a pyridine derivative and an inhibitor of steroid 11-beta-hydroxylase with anti-adrenal activity. Metyrapone inhibits steroid 11-beta-hydroxylase, thereby inhibiting the synthesis of cortisol from 11-deoxycortisol, and corticosterone, the precursor of aldosterone, from deoxycorticosterone in the adrenal gland. Removal of the negative feedback mechanism exerted by cortisol results in increased adrenocorticotropic hormone (ACTH) secretion by the pituitary gland. In turn, continued stimulation of the adrenal gland by ACTH results in the accumulation of corticoid precursors, 11-deoxycortisol and deoxycorticosterone. These corticoid precursors are excreted in urine and may be used as indicators for hypothalamic-pituitary ACTH function.
The 1R isomer of crilvastatin, a pyrrolidone non-competitive inhibitor of hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase.
The 1S isomer of crilvastatin, a pyrrolidone non-competitive inhibitor of hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase.
Visibly abnormal tissue on a magnetic resonance image (MRI) or computed tomography (CT) that does not enhance with contrast and is not edema.
Primitive reflex actions that newborns display in response to specific stimuli. These reflexes are involuntary and most disappear as the infant matures.
A neoplastic, inflammatory, or vascular process in the roof of the skull.
Edema that is characterized by increased permeability of capillary endothelial cells.
The development of a problematic medical situation that occurs concurrently with the birth of a neonate.
The historical fact that a legal or consanguineous brother or sister has died.
The best estimated due date is determined by: last menstrual period (LMP) if confirmed by early ultrasound or no ultrasound performed, or early ultrasound if no known LMP or the ultrasound is not consistent with LMP, or known date of fertilization (e.g. Assisted Reproductive Technology (ART), Intrauterine Insemination (IUI)). Notes: 1. Ultrasound margin of error and ""early"" to be defined by SMFM/ACOG/NICHD workshop. 2. Pregnancy should not be re-dated by a later ultrasound after a best obstetrical estimate of EDD has been established. (adapted from reVITALize)
A disorder characterized by the body's inability to synthesize beta-globin chains, leading to the formation of abnormal hemoglobin and anemia. This inherited autosomal recessive blood disorder is caused by germline mutation of the HBB gene.
A component of the Apgar score, it is the numerical value assigned to the assessment of breathing effort by a neonate. 0 = no spontaneous respirations; 1 = slow or irregular respirations or a weak cry; 2 = strong, consistent respirations with a robust cry.
A component of the Apgar score, it is the numerical value assigned to an assessment of the circulatory status of a neonate. 0 = no pulse; 1 = rate less than 100 beats per minute; 2 = rate greater than 100 beats per minute.
A component of the Apgar score, it is the numerical value assigned to an assessment of the residual muscle tension of a neonate. 0 = flaccid; 1 = flexion of extremities; 2 = active motion.
A component of the Apgar score, it is the numerical value assigned to the neonate's response to stimuli, such as a mild pinch. 0 = no reaction; 1 = grimace; 2 = grimace with a cough, sneeze, or vigorous cry.
A component of the Apgar score, it is the numerical value assigned to an assessment of the color of the skin of a neonate. 0 = pale blue; 1 = pink body and pale blue extremities; 2 = pink body and extremities.
A disorder characterized by the body's inability to metabolize galactose. This type of galactosemia is caused by germline mutations in the GALT gene which leads to the inhibition in the activity of the enzyme galactose-1-phosphate uridyl transferase.
A dispirotripiperazine derivative and alkylating agent with potential antineoplastic and anti-inflammatory activities. Dibrospidium chloride has been examined for the treatment of bone cancer.
An N-L-leucyl prodrug of the anthracycline doxorubicin, with antineoplastic activity. Leurubicin is converted to its active form doxorubicin in or on tumor cells by hydrolytic enzymes.
An anthracycline derivative with antineoplastic activity developed to circumvent doxorubicin resistance.
A 9-aza-anthrapyrazole-based antineoplastic antibiotic. Nortopixantrone intercalates into DNA, induces single- and double-stranded DNA breaks and inhibits topoisomerase II, thereby inhibiting DNA replication and repair as well as RNA and protein synthesis. Nortopixantrone is less cardiotoxicity than anthracyclines.
The hydrochloride salt form of razaxaban, an orally active, 1,2-benzisoxazole-containing, inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Razaxaban forms an isoxazole-ring opened, stable, benzamidine metabolite which is subsequently excreted through the bile.
An antifungal agent with particular activity against the genus Trichophyton.
An antilipidemic agent based on the carbon skeleton of cholesterol. Colestolone targets sterol regulatory element binding protein (SREBP) which reduces the transcription of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) gene, the rate-limiting enzyme in the sterol pathway. Colestolone is also metabolized by cells into polar sterols, which are known to inhibit HMGCR enzymatic activity.
A thyroid hormone analog with hypocholesterolemic properties. Eprotirome reduces serum LDL cholesterol levels by increasing hepatic clearance due to increased expression of the hepatic LDL-receptor gene, and also reduces the serum level of Lp(a) lipoprotein. This drug was designed to have minimal uptake in nonhepatic tissues thereby avoiding many of the adverse effects associated with thyroid hormone treatment.
An acetate salt form of lapaquistat, a squalene synthase inhibitor investigated for the treatment of hypercholesterolemia.
A selective small-molecule activator of protein kinase C (PKC) isolated from the plant Euphorbia peplus with potential antineoplastic activity. Ingenol mebutate activates various protein kinase C (PKC) isoforms, thereby inducing apoptosis in some tumor cells, including myeloid leukemia cells, melanoma cells, and basal cell carcinoma cells. The PKC family consists of signaling isoenzymes that regulate many cell processes including proliferation, differentiation, and apoptosis.
A derivative of isoniazid with tuberculostatic activity.
A dual peroxisome proliferator-activated receptor (PPAR) agonist, with hypoglycemic activity. In addition to its beneficial effects on glucose and triglyceride (TG) plasma levels, cevoglitazar also decreases body weight gain and adiposity.
A potent, long-acting, selective, orally bioavailable, pyrrolidinone-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Carmegliptin shows extensive tissue distribution and is excreted unchanged in the urine and bile.
The dihydrochloride salt form of carmegliptin, a potent, long-acting, selective, orally bioavailable, pyrrolidinone-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Carmegliptin shows extensive tissue distribution and is excreted unchanged in the urine and bile.
A very rare dendritic cell tumor affecting the lymph nodes, spleen, and soft tissues. Morphologically it is similar to the interdigitating dendritic cell sarcoma or follicular dendritic cell sarcoma. The tumor cells are positive for cytokeratin and CD68. Clinical outcome is variable.
A very rare dendritic cell tumor composed of spindle to ovoid cells with a phenotype that is similar to the Langerhans cells. Patients usually present with cutaneous papules, nodules, and plaques. Systemic symptoms are usually absent. The clinical course is variable.
Juvenile xanthogranuloma disseminated to extracutaneous sites including mucosal surfaces, lung, central nervous system, pituitary, lymph nodes, eye, liver, and bone marrow. It is characterized by the presence of lipid-laden, foamy histiocytes and Touton-type giant cells forming nodules in the affected anatomic sites.
An epithelioid cell type gastrointestinal stromal tumor with an indolent clinical course.
An epithelioid cell type gastrointestinal stromal tumor with an aggressive clinical course.
A molecular interaction in which a small molecule or structure becomes trapped, usually in a larger molecule or structure, due to non-covalent interactions.
A folate receptor-targeting cytotoxic drug conjugate consisting of a folate vitamin analogue linked to a vinca alkaloid microtubule destabilizing agent with potential antineoplastic activity. Mediated through its folate moiety, folate receptor-targeted vinca alkaloid EC0489 delivers the cytotoxic vinca alkaloid moiety directly to cells expressing folic acid receptors, frequently upregulated in many types of tumor cells. After ligand-receptor internalization, the vinca alkaloid moiety binds to tubulin and disrupts microtubule assembly-disassembly dynamics, resulting in cell cycle arrest and apoptosis. The relative tumor cell specificity of this agent reduces the toxicity profile of its vinca alkaloid moiety.
A long-acting recombinant fusion protein incorporating human serum albumin (HSA)-derived and human granulocyte colony stimulating factor (G-CSF)-derived moieties with potential granulopoietic activity. G-CSF, a naturally occurring cytokine, stimulates the production of granulocytes and stem cells in the bone marrow and their release into the blood; it also stimulates the differentiation, function, and survival of neutrophil precursors and mature neutrophils. Albumin fusion may promote an increased serum half-life and bioavailability of the G-CSF moiety of this fusion protein.
A recombinant form of the naturally-occurring polypeptide human epidermal growth factor with potential epithelial regenerative and cytoprotective activities. Upon topical application, recombinant human epidermal growth factor (rhEGF) may stimulate epithelial proliferation, differentiation and migration, which may result in the acceleration of epithelial regeneration and wound healing. In addition, rhEGF may attenuate epithelial cytotoxicities related to chemotherapy and/or radiotherapy.
A humanized monoclonal antibody directed against human hepatocyte growth factor (HGF) with potential antineoplastic activity. Anti-HGF monoclonal antibody TAK-701 binds to the soluble ligand HGF, preventing HGF binding to and activation of the HGF receptor c-Met and so the activation of the c-Met signaling pathway; this may result in the induction of cell death in c-Met-expressing tumor cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in a variety of tumor cell types, plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis.
An orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor prodrug, with potential antiserotonergic activity. Upon administration, telotristat etiprate is converted to its active moiety, telotristat (LP-778902), which binds to and blocks the activity of TPH. This may result in a reduction in peripheral serotonin (5-HT) production and improvement of serotonin-mediated gastrointestinal effects such as severe diarrhea. TPH, the rate-limiting enzyme in serotonin biosynthesis, is overexpressed in carcinoid tumor cells.
A molecular genetic abnormality that refers to the presence of a mutation in the ALK gene.
Expression of fusion protein transcripts resulting from genetic alterations of the anaplastic lymphoma kinase (ALK) gene.
Recession of the gum that exposes the furcation of a multirooted tooth.
Any abnormal inclincation of the occlusal plane.
An acute leukemia of ambiguous lineage. It is characterized by the presence of either separate populations of blasts of more than one lineage, or one population of blasts co-expressing markers of more than one lineage.
A rare mixed phenotype acute leukemia in which the blasts also carry the translocation t(9;22)(q34.1;q11.2) by karyotypic analysis or the BCR-ABL1 translocation by FISH or PCR. The prognosis is usually unfavorable.
A rare mixed phenotype acute leukemia in which the blasts also carry a translocation (v; 11q23.3) involving the KMT2A gene. The prognosis is usually unfavorable.
A rare mixed phenotype acute leukemia in which the blasts express T-lymphoid and myeloid lineage markers but are negative for MLL translocation and t(9;22)(q34;q11.2) translocation. The prognosis is usually unfavorable.
A provisional entity describing precursor lymphoid neoplasms that express CD56 and immature T-cell markers, lack B-lymphoid and myeloid markers, and have the immunoglobulin and T-cell receptor genes in the germline configuration.
An antiparasitic agent used to control coccidiosis in the chicken industry.
A sulfamoylbenzoic acid-based agent and indapamide analog, with diuretic activity. Zidapamide, formerly known as isodapamide, acts in a similar manner as the thiazide-like diuretic indapamide. This agent has never been marketed.
Coagulation factor X (488 aa, ~55 kDa) is encoded by the human F10 gene. This protein is involved in proteolysis and blood coagulation.
A lipophilic, weak base with potassium-competitive acid blocking (P-CAB) activity. Linaprazan concentrates highly in the gastric parietal cell canaliculus and on entering this acidic environment is instantly protonated and binds competitively and reversibly to the potassium binding site of the proton pump hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase), thereby inhibiting the pump's activity and the parietal cell secretion of H+ ions into the gastric lumen, the final step in gastric acid production.
Myeloid neoplasms occurring in individuals with Down syndrome. There is an increased risk of acute leukemias in both children and adults with Down syndrome. In particular, the incidence of acute myeloid leukemia in Down syndrome children of less than five years of age is particularly high, it is usually an acute megakaryoblastic leukemia, and is associated with GATA1 gene mutation. This group of disorders also includes the entity transient abnormal myelopoiesis which occurs in neonates and is associated with GATA1 gene mutation.
A change in the nucleotide sequence of the GATA1 gene.
An I 131 radioiodinated synthetic analogue of the neurotransmitter norepinephrine, manufactured with a proprietary process, with radioisotopic and potential antineoplastic activities. Cold contaminant-free iobenguane I 131 (MIBG) localizes to adrenergic tissue and may be used to image or eradicate tumor cells that accumulate and metabolize norepinephrine. This agent is manufactured using a technology that avoids the production of unwanted ""cold contaminants"" (i.e., carrier molecules), which may cause undesirable side effects and compete with MIBG for binding on target receptor sites.
A humanized monovalent monoclonal antibody directed against the hepatocyte growth factor receptor (c-Met) with potential antineoplastic activity. Anti-MET monoclonal antibody MetMAb binds to the extracellular domain of c-Met, preventing the binding of its ligand, hepatocyte growth factor (HGF); the activation of the c-Met signaling pathway is thus inhibited, which may result in cell death in c-Met-expressing tumor cells. c-Met, a receptor tyrosine kinase, is overexpressed on the cell surfaces of a variety of cancer cell types and may play a key role in their proliferation, invasion and survival.
A small-molecule inhibitor of Aurora kinases A, B and C with potential antineoplastic activity. Aurora kinase inhibitor AMG 900 selectively binds to and inhibits the activities of Aurora kinases A, B and C, which may result in inhibition of cellular division and proliferation in tumor cells that overexpress these kinases. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis and are overexpressed by a wide variety of cancer cell types.
A preparation of autologous CD8+ (cytotoxic) T-lymphocytes sensitized to cancer-testis antigen NY-ESO-1 antigen with potential immunostimulating and antineoplastic activities. Autologous CD8+ T-lymphocytes, isolated from a melanoma patient, are exposed to an NY-ESO-1 peptide ex vivo, expanded, and reintroduced into the patient; these tumor-reactive T-cells may stimulate a host immune response against tumor cells expressing the NY-ESO-1 antigen, resulting in tumor cell lysis. NY-ESO-1, an antigen found in normal testis, may be upregulated in various cancers, including bladder, breast, hepatocellular, melanoma, and prostate cancers.
Peripheral blood stem cells (PBSCs) transduced with the retroviral vector M87o encoding for the HIV-1-entry inhibitor peptide membrane-anchored antiviral peptide C46 (maC46). Expression of C46 by M87o-transduced CD34+ peripheral blood stem cells may prevent the fusion of viral and cellular membranes, thereby inhibiting HIV-1 entry. C46 is a membrane-anchored peptide encoding amino acids 628 to 673 of the HIV-1 entry inhibitory transmembrane glycoprotein gp41.
A cancer vaccine containing xenogenic DNA from rhesus macaque (Macaca mulatta) that encodes prostate specific antigen (PSA) with potential immunostimulating and antineoplastic activities. Upon repeated intradermal administration via electroporation, pVAXrcPSAv53l vaccine may induce a cytotoxic T-lymphocyte (CTL) response against PSA-expressing prostate cancer cells. Rhesus PSA is 89% homologous to human PSA.
A cationic lipid DNA complex (CLDC) consisting of DOTIM/cholesterol liposomes and plasmid DNA, containing immunostimulatory CpG and non-CpG motifs, with potential immunostimulating and antineoplastic activities. Upon systemic administration, TLR-directed cationic lipid-DNA complex JVRS-100 enters dendritic cells (DCs) and macrophages; immunostimulatory DNA binds to and activates Toll-like receptors (TLRs), which may result in the generation of anti-tumor natural killer (NK) cell and T-cell responses by the innate immune system. In addition, as a vaccine adjuvant, this agent may induce a strong cytotoxic T-lymphocyte (CTL) response to co-administered antigen.
A radiolabeled divalent histamine-succinyl-glycine (HSG) hapten-peptide linked with the macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the radionuclide lutetium (Lu) 177. After pretargeting with a bispecific monoclonal antibody (BiMoAB) directed against both a tumor associated antigen (TAA) and the HSG hapten-peptide, the HSG portion of administered Lu-177-labeled di-HSG-DOTA peptide IMP-288 binds the anti-HSG portion of the BiMoAB; Lu-177 radioisotopic activity localized to tumor cells bearing the TAA can then be visualized scintigraphically.
A radiolabeled divalent histamine-succinyl-glycine (HSG) hapten-peptide linked with the macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the radionuclide indium (In) 111. After pretargeting with a bispecific monoclonal antibody (BiMoAB) directed against both a tumor associated antigen (TAA) and the HSG hapten-peptide, the HSG portion of administered indium-In-labeled di-HSG-DOTA peptide IMP-288 binds the anti-HSG portion of the BiMoAB; In-111 radioisotopic activity localized to tumor cells bearing the TAA can then be visualized scintigraphically.
An orally bioavailable leucine enriched essential amino acid dietary supplement with potential anti-cachexia activity. Leucine-enhanced essential amino acid nutritional supplement may stimulate the mammalian target of rapamycin (mTOR) signaling pathway, which may promote protein synthesis in muscle cells. Although the exact mechanism by which leucine and other essential amino acids stimulate mTOR has yet to be fully elucidated, leucine may stimulate mTOR by inhibiting adenosine monophosphate protein kinase (AMPK), which negatively controls mTOR signaling.
A humanized monoclonal antibody directed against the pro-inflammatory cytokine interleukin-6 (Il-6) with potential immunomodulating activity. Upon administration, anti-interleukin 6 monoclonal antibody ALD518 binds to and blocks the activity of IL-6, which may mitigate the catabolic effects of IL-6.
A recombinant 19 kDa protein derived from the Apicomplexa protozoan Eimeria with potential immunostimulating and antitumor activities. Upon administration, innate immunostimulator rBBX-01 activates dendritic cells (DCs), stimulates the Toll-like receptor 11 (TLR-11)-mediated release of interleukin-12 (Il-12) from DCs, and induces a T-helper 1 (Th1) type immune response, which may induce an immune response against tumor cells. Infection with Eimeria, a coccidian commonly infecting the intestine, may be negatively correlated with tumorigenesis.
A peptide that mimics naturally occurring interleukin-11 (IL-11) with interleukin receptor binding activity. Upon administration, bone metastasis targeting peptide-11 (BMTP-11) binds to interleukin-11 receptor alpha (IL-11Ra) BMTP-11. This agent might be used to deliver therapeutic agents specifically to IL-11Ra-expressing tumor cells while sparing normal cells. IL-11Ra is a cell surface receptor that may be overexpressed by osteosarcoma cells and by prostate cancer cells in prostate cancer bone metastases.
The orally bioavailable bismesylate salt of a potent small-molecule thieno[3,2-d]pyrimidine inhibitor of the class I phosphatidylinositol 3 kinase (PI3K) isoforms p100alpha and p100delta with potential antineoplastic activity. PI3K inhibitor GDC-0941 selectively binds to PI3K isoforms in an ATP-competitive manner, inhibiting the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway; inhibition of tumor cell growth, motility and survival in susceptible tumor cell populations may result. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis; dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
Early-to late-stage myeloid progenitor cells derived from adult human stem cells with potential hematopoietic activity. Upon infusion, human myeloid progenitor cells CLT-008 proliferate into mature myeloid cells, including granulocytes, macrophages, platelets, and erythrocytes. These myeloid progenitor cells die within forty-five days after a burst of hematopoiesis. This agent cannot create lymphoid cells, including T cells associated with graft-versus-host disease (GVHD).
A selective gamma secretase (GS) inhibitor with potential antitumor activity. Gamma secretase inhibitor PF-03084014 binds to GS, blocking proteolytic activation of Notch receptors; Notch signaling pathway inhibition may follow, which may result in the induction of apoptosis in tumor cells that overexpress Notch. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth and survival.
A fusion protein containing two thrombospondin (TSP-1)-derived nonamer peptides covalently attached, via a proprietary diketone linker, to a proprietary humanized catalytic monoclonal aldolase monoclonal antibody with potential antiangiogenic and antineoplastic activities. The TSP-1 mimetic peptide moieties of TSP-1 mimetic fusion protein CVX-045 bind to TSP-1 receptors, such as CD36, and inhibit tumor angiogenesis, which may result in the inhibition of tumor cell proliferation. The proprietary humanized catalytic monoclonal aldolase monoclonal antibody contains reactive lysine residues in its binding sites, which react covalently with compounds having a diketone function; the TSP-1 mimetic peptide moieties are then covalently attached to the diketone linkers via a proprietary spacer.
An autologous tumor cell vaccine containing irradiated breast cancer cells transfected with the granulocyte macrophage-colony-stimulating factor (GM-CSF) gene with potential antineoplastic activity. Autologous breast cancer cells are transduced ex vivo with an adenovirus vector encoding the GM-CSF gene and irradiated and then reintroduced into the patient. Upon repeated subcutaneous administration of the vaccine, autologous GM-CSF-secreting breast cancer cells secrete GM-CSF, which may stimulate a tumor-specific cytotoxic T-lymphocyte (CTL) response.
An orally bioavailable Polo-like kinase 1 (Plk1) inhibitor with potential antineoplastic activity. Polo-like kinase 1 inhibitor MK1496 selectively inhibits Plk1, inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner.
A lipid nanoparticle formulation containing two small interfering RNAs (siRNAs) for kinesin spindle protein (KSP) and vascular endothelial growth factor (VEGF) with potential antitumor activity. Upon intravenous administration, the siRNAs in KSP/VEGF siRNAs ALN-VSP02ALN bind to both KSP and VEGF messenger RNAs (mRNAs), preventing translation of KSP and VEGF proteins; this may result in growth inhibition of tumor cells that overexpress KSP and VEGF. VEGF and KSP are upregulated in many tumor cells and play an important role in tumor proliferation and survival.
A myelodysplastic/myeloproliferative neoplasm arising as a result of the mutagenic effect of chemotherapy agents and/or radiation that are used for the treatment of neoplastic or non-neoplastic disorders.
The dimaleate salt of a synthetic, noncardiotoxic aza-anthracenedione analogue with potential antineoplastic activity. Pixantrone intercalates into DNA and induces topoisomerase II-mediated DNA strand crosslinks, resulting in inhibition of DNA replication and tumor cell cytotoxicity.
A small-molecule pan-PIM protein kinase inhibitor with potential antineoplastic activity. PIM kinase inhibitor SGI-1776 binds to and inhibits the activities of PIM-1, -2 and -3 serine/threonine kinases, which may result in the interruption of the G1/S phase cell cycle transition, the expression of pro-apoptotic Bcl2 proteins and tumor cell apoptosis. PIM kinases play key roles in cell cycle progression and apoptosis inhibition and may be overexpressed in various malignancies.
An injectable form of the sodium salt of the fluorophore fluorescein. Fluorescein responds to electromagnetic radiation between the wavelengths of 465-490 nm and fluoresces, emitting light at wavelengths of 520-530 nm that can be detected visually.
A humanized IgG1 monoclonal antibody directed against human endosialin/TEM1 (tumor endothelial marker;CD248) with potential anti-angiogenic and antineoplastic activities. Anti-endosialin/TEM1 monoclonal antibody MORAb-004 binds to and inhibits the activity of cell surface protein endosialin/TEM1, which may result in the inhibition of angiogenesis, tumor cell proliferation and metastasis. Endosialin/TEM1 plays a key role in angiogenesis and may be overexpressed on tumor stromal cells and endothelial cells.
A cancer vaccine containing plasmid DNA encoding human prostatic acid phosphatase (PAP) (pTVG-HP) with potential immunostimulatory and antineoplastic activities. Upon administration, pTVG-HP plasmid DNA vaccine may stimulate the host immune system to generate a cytotoxic T lymphocyte (CTL) response against PAP-expressing prostate cancer cells. PAP or prostatic specific acid phosphatase (PSAP) is a tumor associated antigen (TAA) that may be overexpressed in prostate cancer.
A preparation of autologous human T-lymphocytes isolated from renal cell cancer (RCC) patient and transduced with 2G-1 TCR, a retroviral vector encoding the alpha and beta chains of a T-cell receptor that recognizes TNF-related apoptosis inducing ligand (TRAIL) bound to death receptor 4 (DR4), with potential immunostimulating and antineoplastic activities. After transduction, expansion in culture, and introduction into the RCC patient, 2G-1 TCR retroviral vector-transduced lymphocytes may stimulate a cytotoxic T lymphocyte (CTL) response against RCC cells with TRAIL bound to DR4 on their surfaces. TRAIL, a member of the TNF superfamily, is a homotrimeric type II membrane protein that rapidly induces oligomerization of receptor intracellular death domains and apoptosis in a variety of tumor cells when bound to its receptors; DR4 (TRAIL receptor 1), a member of the TNF receptor family, is overexpressed by a variety of malignant cell types.
A preparation of donor T-lymphocytes that are transfected with a retroviral vector encoding a chimeric suicide gene consisting of the extracellular and transmembrane domains of human CD34 and mutant 75 of the herpes simplex virus thymidine kinase (HSV-TK75) with potential controllable immunomodulating activity. Donor T cell therapy following allogeneic hematopoietic stem cell (HSC) transplantation may result in a graft-versus-leukemia (GVL) and help control transplant-related viral infections. In the event that graft-versus-host disease (GVHD) develops due to donor lymphocyte infusion, CD34/TK75-transduced donor lymphocytes may be selectively eliminated by administration of the prodrug antiviral agent ganciclovir GCV. In CD34/T75-transduced donor lymphocytes, GCV is phosphorylated by expressed HSV-TK75 to its monophosphate form and, subsequently, converted into its active triphosphate form, which specifically kills the donor lymphocytes. The expressed CD34 moiety of the chimeric suicide gene serves as a selection marker; mutant 75 of HSV-TK confers increased GCV sensitivity.
A fusion protein consisting of a mouse-human chimeric antibody directed against DNA released by necrotic tumor cells fused to two molecules of a genetically modified human interleukin-2 (IL-2) with potential antineoplastic activity. Upon administration, the antibody moiety of immunocytokine NHS-IL2-LT binds to DNA released by necrotic tumor cells located primarily at the core of necrotic solid tumors, delivering the IL-2 moiety. In turn, the IL-2 moiety of this agent activates the immune system to mount a cytotoxic T lymphocyte response against nearby tumor cells.
A vaccine consisting of irradiated human fetal lung fibroblasts (Medical Research Council 5 or MRC-5) transfected with autologous non-small cell lung cancer (NSCLC)-derived DNA with potential immunostimulatory and antineoplastic activities. Upon administration, autologous NSCLC DNA-transfected semi-allogeneic fibroblasts MRC-5 vaccine expresses NSCLC tumor-associated antigens (TAAs) in addition to MHC class I-determinants and the co-stimulatory molecule B7.1, which may induce a cytotoxic T-lymphocyte (CTL) response against NSCLC cells. The MRC-5 cell line is a human diploid lung fibroblast cell line extablished in 1966.
A vaccine preparation containing mucus 1 (MUC1) peptide and the adjuvant poly-ICLC with potential immunostimulatory and antineoplastic activities. Upon administration, MUC1 peptide-poly-ICLC adjuvant vaccine may induce the host immune system to mount a cytotoxic T cell response against MUC1-expressing tumor cells. MUC1, a tumor associated antigen normally present on the lining of the human colon, may be overexpressed and/or mutated in a variety of cancer cell types. The adjuvant poly-ICLC, a ligand for toll-like receptor-3, induces the release of cytokines which may help boost the immune response against MUC1.
An orally bioavailable cell division cycle 7 homolog (CDC7) kinase inhibitor with potential antineoplastic activity. CDC7 kinase inhibitor BMS-863233 binds to and inhibits the activity of CDC7, which may result in the inhibition of DNA replication and mitosis, the induction of tumor cell apoptosis, and the inhibition of tumor cell proliferation in CDC7-overexpressing tumor cells. CDC7, a serine-threonine kinase overexpressed in a variety of tumor cell types, plays an essential role in the initiation of DNA replication by activating origins of replication.
A drug-device combination product consisting of small polymeric beads impregnated with the anthracycline antibiotic doxorubicin with potential antineoplastic activity. The beads consist of polyvinyl alcohol (PVA) microspheres modified with sulfonic acid groups and loaded with doxorubicin. During transarterial chemoembolization (TACE), doxorubicin-eluting beads embolize to the tumor vasculature and release cytotoxic doxorubicin, which may result in both ischemic necrosis of tumor tissue due to mechanical blockage of the tumor vasculature and doxorubicin-mediated inhibition of tumor cell proliferation.
A peptide vaccine consisting of 10 synthetic long peptides (SLPs), 25-30 amino acids in size and derived from the middle portion of p53 (amino acids 70-251), mixed with the adjuvant Montanide ISA-51 with potential immunostimulatory and antitumor activities. Upon administration, p53 synthetic long peptide (70-251) vaccine may stimulate the host immune system to mount a cytotoxic T-cell lymphocyte (CTL) response against p53-expressing tumor cells. p53, a tumor associated antigen (TAA), may be overexpressed in variety of cancer cell types.
A cancer vaccine containing HLA-A*2402-restricted epitope peptides URLC10 (up-regulated lung cancer 10) with potential immunostimulatory and antineoplastic activities. Upon administration, HLA-A*2402-restricted URLC10 peptides vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against URLC10-expressing tumor cells. URLC10, a tumor associated antigen, is often overexpressed in lung, esophageal and gastric cancers. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
An acute myeloid leukemia associated with t(6;9)(p23;q34.1) resulting in DEK-NUP214(CAN) fusion protein expression. It is often associated with multilineage dysplasia and basophilia. It affects both children and adults and it usually has an unfavorable clinical outcome.
An acute myeloid leukemia associated with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2) resulting in the reposition of a distal GATA2 enhancer to activate MECOM expression. It may present de novo or follow a myelodysplastic syndrome. The clinical course is aggressive.
An acute myeloid leukemia associated with t(1;22)(p13.3;q13.3) resulting in the expression of RBM15-MKL1 fusion protein. It affects infants and children and usually shows megakaryocytic maturation.
Mutation of the nucleophosmin gene. It is seen in acute myeloid leukemias usually associated with a normal karyotype.
A term referring to acute myeloid leukemias associated with gene mutations most often of the FLT3, NPM1, and CEBPA genes. These leukemias may have normal karyotypes or additional chromosomal aberrations.
An acute myeloid leukemia with mutation of the nucleophosmin gene. It is usually associated with normal karyotype and frequently has myelomonocytic or monocytic features. It usually responds to induction therapy.
An acute myeloid leukemia with mutations of the CEBPA gene.
Death that is attributed to the progression of a disease or pre-existing condition, and which is not attributable to any outside action or force.
An indication or description of whether the adverse event caused the subject to discontinue from the study.
A situation that imperils the existence of an entity.
A decision that an observation or result is outside the parameters considered normal.
An indication or description that an event occurs concurrently with a substance overdose.
An indication or description that a specific activity resulted in the death of a subject.
An indication or description that a relationship to cancer exists.
A finding that has treatment or management implications for a patient's condition.
An indication or description of a correlation between death and another event.
An indication or description of the correlation between a finding or event of interest and a treatment outside the specifications of a study.
A myelodysplastic syndrome characterized by dysplastic changes involving only one myeloid cell lineage in the bone marrow. It primarily affects older adults and includes refractory anemia, refractory neutropenia, and refractory thrombocytopenia.
A myelodysplastic syndrome characterized by the presence of at least 10% dysplastic neutrophils in the bone marrow or the peripheral blood.
A myelodysplastic syndrome characterized by the presence of at least 10% dysplastic megakaryocytes, found within at least 30 megakaryocytes examined in the bone marrow.
Myelodysplastic syndrome with excess blasts associated with significant reticulin fibrosis of the bone marrow.
The most common subtype of the myelodysplastic syndromes affecting children. It is characterized by persistent cytopenia with less than 5% blasts in the bone marrow and less than 2% blasts in the peripheral blood.
Mutation of the protein tyrosine phosphatase, non-receptor type 11 gene. It is seen in cases of juvenile myelomonocytic leukemia.
A myelodysplastic/myeloproliferative neoplasm with morphologic and clinical characteristics of refractory anemia with ring sideroblasts, marked thrombocytosis, and abnormal megakaryocytes.
The citrate salt form of ixazomib, an orally bioavailable second generation proteasome inhibitor (PI) with potential antineoplastic activity. Ixazomib inhibits the activity of the proteasome, blocking the targeted proteolysis normally performed by the proteasome, which results in an accumulation of unwanted or misfolded proteins; disruption of various cell signaling pathways may follow, resulting in the induction of apoptosis. Compared to first generation PIs, second generation PIs may have an improved pharmacokinetic profile with increased potency and less toxicity. Proteasomes are large protease complexes that degrade unneeded or damaged proteins that have been ubiquinated.
A prostate cancer vaccine containing mRNAs encoding prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), prostate stem cell antigen (PSCA) and six-transmembrane epithelial antigen of the prostate (STEAP), with potential antitumor activity. Upon administration, mRNA-derived prostate cancer vaccine CV9103 may stimulate the immune system to mount a cytotoxic T lymphocyte response (CTL) against PSA-, PSMA-, PSCA- and STEAP-expressing prostate tumor cells. The mRNA used in this vaccine is modified and formulated to have enhanced translational potency and adjuvant activities. PSA, PSMA, PSCA and STEAP may be upregulated in prostate cancer cells; their expression in prostate cancer has been correlated with disease progression.
A powder formulation containing a triple helix beta-glucan, isolated from the cell walls of the shiitake mushroom (Lentinula edodes), with potential immunostimulating activity. The beta-glucan in beta-glucan MM-10-001 binds to a lectin site within the complement receptor 3 (CR3 or iC3b receptor) on leukocytes, priming the receptor to trigger cytotoxic degranulation of leukocytes when leukocyte CR3 binds to iC3b-opsonized tumor cells. iC3b is the proteolyticly inactive product of the complement cleavage fragment C3b.
A pegylated formulation of a recombinant form of human hyaluronidase with potential antitumor activity. Upon intravenous administration, pegylated recombinant human PH20 degrades hyaluronic acid (HA) coating tumor cells, which may result in the inhibition of tumor cell growth. In addition, the degradation of HA may result in a lowering of the interstitial fluid pressure (IFP), allowing better penetration of chemotherapeutic agents into the tumor bed. HA is a glycosaminoglycan found in the extracellular matrix (ECM) that is frequently overproduced by various tumor cell types. The presence of HA in tumors correlates with increased tumor cell growth, metastatic potential, tumor progression, increased resistance to chemotherapeutic agents, and an elevation in tumor IFP.
An enteric-coated orally bioavailable formulation of the hydrochloride salt of a small-molecule agonist for transient receptor potential melastatin member 8 (TRPM8 or Trp-p8) with potential antineoplastic activity. The active ingredient in enteric-coated TRPM8 agonist D-3263 hydrochloride binds to and activates TRPM8, which may result in an increase in calcium and sodium entry; the disruption of calcium and sodium homeostasis; and the induction of cell death in TRPM8-expressing tumor cells. This agent may decrease dihydrotestosterone (DHT) levels, which may contribute to its inhibitory effects on prostate cancer and BPH. TRPM8 is a transmembrane calcium channel protein that is normally expressed in prostate cells and appears to be overexpressed in benign prostatic hyperplasia (BPH) and in prostate cancer.
A synthetic peptide cancer vaccine consisting of HLA-A2-restricted peptides derived from glioma-associated antigens (GAA) with potential immunostimulating and antineoplastic activities. Upon administration, HLA-A2-restricted synthetic glioma antigen peptides vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the corresponding GAAs, resulting in glioma tumor cell lysis. HLA-A2 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A2 may improve antigenic peptide immunogenicity.
A small-molecule inhibitor of the serine-threonine kinase Aurora B with potential antineoplastic activity. Aurora B kinase inhibitor TAK-901 binds to and inhibits the activity of Aurora B, which may result in a decrease in the proliferation of tumor cells that overexpress Aurora B. Aurora B is a positive regulator of mitosis that functions in the attachment of the mitotic spindle to the centromere; the segregation of sister chromatids to each daughter cell; and the separation of daughter cells during cytokinesis. This serine/threonine kinase may be amplified and overexpressed by a variety of cancer cell types.
A cancer vaccine containing a plasmid encoding the mammaglobin-A gene with potential immunostimulating and antineoplastic activities. Upon administration, mammaglobin-A DNA vaccine may induce both humoral and cytotoxic T lymphocyte (CTL) immune responses against tumor cells that express mammaglobin-A, which may result in decreased tumor growth. The 10 kiloDalton (kD) glycoprotein mammglobin-A is expressed in over 80% of human breast cancers.
A selective small-molecule inhibitor of the proto-oncogene c-Met with potential antineoplastic activity. c-Met inhibitor AMG 208 inhibits the ligand-dependent and ligand-independent activation of c-Met, inhibiting its tyrosine kinase activity, which may result in cell growth inhibition in tumors that overexpress c-Met. C-Met encodes the hepatocyte growth factor receptor tyrosine kinase, plays an important role in epithelial cell proliferation and has been shown to be overexpressed in a variety of cancers.
An oral suspension containing diphenydramine hydrochloride, dexamethasone and nystatin, with anithistaminic, antiinflammatory, and antifungal activities. Diphenhydramine hydrochloride/dexamethasone/nystatin magic mouthwash inhibits the cytokine-mediated inflammation and yeast colonization of the oral mucosa associated with chemotherapy and radiation therapy.
Microporous hydrospheres of polyvinylalcohol (PVA) impregnated with irinotecan with potential antineoplastic activity. In transarterial chemoembolization (TACE), irinotecan-eluting beads are administered into blood vessels that feed the tumor, occluding tumor blood vessels and inducing ischemic tumor necrosis while simultaneously delivering high-dose chemotherapy locally. Irinotecan, a semisynthetic derivative of camptothecin, inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death.
A hydroxamic acid-derived histone deacetylase (HDAC) inhibitor with potential antineoplastic activity. CHR-2845 inhibits HDAC leading to an accumulation of highly acetylated histones, which may result in chromatin remodeling, inhibition of tumor oncogene transcription, inhibition of tumor cell division, and the induction of tumor cell apoptosis. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins; this agent may specifically target HDACs in cells of the monocyte-macrophage lineage.
An orally bioavailable nanoparticle albumin-bound inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor AB-010 selectively binds to Hsp90, inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. This agent may inhibit the growth of a wide variety of cancer cell types; the incorporation of albumin into its formulation may facilitate its endothelial transcytosis through the gp60-regulated albumin transport pathway. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding and degradation of many oncogenic signaling proteins.
An orally bioavailable inhibitor of the ADAM (A Disintegrin And Metalloprotease) family of multifunctional membrane-bound proteins with potential antineoplastic activity. Sheddase inhibitor INCB007839 represses the metalloproteinase """"sheddase"""" activities of ADAM10 and ADAM17, which may result in the inhibition of tumor cell proliferation. The metalloproteinase domains of ADAMs cleave cell surface proteins at extracellular sites proximal to the cell membrane, releasing or """"shedding"""" soluble protein etcodomains from the cell surface; the disintegrin domains of these multifunctional proteins interact with various components of the extracellular matrix (ECM). ADAM10 processes particular epithelial growth factor receptor (EGFR) ligands and appears to regulate Notch signaling through the cleavage of Notch and its related ligand delta-like ligand-1 (Dll-1). ADAM17 (also known as Tumor necrosis factor-Converting Enzyme or TACE) is involved in processing tumor necrosis factor (TNF) from its membrane bound precursor to its soluble circulating form and in processing ligands for the epidermal growth factor receptor (EGFR) family.
A small-molecule inhibitor of the kinesin-related motor protein Eg5 with potential antineoplastic activity. Eg5 kinesin-related motor protein inhibitor ARQ 621 selectively inhibits the activity of Eg5, which may result in mitotic disruption, apoptosis and cell death. The ATP-dependent Eg5 kinesin-related motor protein (also known as KIF11 or kinesin spindle protein-5) is a plus-end directed kinesin motor protein involved in the regulation of spindle dynamics, including assembly and maintenance, during mitosis.
An analogue of the nucleoside deoxycytidine with potential antineoplastic activity. Nucleoside analogue TAS-109 is incorporated into DNA and directly inhibits the activity of DNA polymerase, which may result in inhibition of DNA replication and cell cycle arrest in the S and G2/M phases, DNA fragmentation, and tumor cell apoptosis.
A benign melanocytic nevus surrounded by eczematous changes.
A chronic fibrotic inflammatory process affecting the salivary gland. Signs and symptoms include firm and painful swelling of the salivary gland, often associated with the presence of salivary gland stones.
An oncocytoma with cystic degenerative changes.
A premalignant neoplastic lesion of the liver. It is characterized by the presence of hepatocytes with enlarged nuclei and cytoplasm, nuclear pleomorphism, multinucleation, and hyperchromasia.
A chronic inflammatory process characterized by the accumulation of a small number of lymphocytes and plasma cells.
A morphologic finding indicating the presence of abnormally large nucleated erythroblasts in the bone marrow.
A morphologic finding indicating lack of synchronous maturation of the cytoplasm and the nucleus.
Cellular damage due to diminished oxygen supply to the tissues. The changes may be mild and associated with chronic inflammation, or severe and associated with ulceration, necrosis, and hemorrhage.
A morphologic finding indicating the presence of wrinkles in the basement membrane of the glomeruli.
A morphologic finding indicating the presence of nuclear or cytoplasmic viral inclusion bodies.
Chronic colitis with superimposed neutrophilic mucosal infiltrates. It is usually seen during exacerbations of inflammatory bowel disease.
A finding indicating shrinkage of the tissue volume of the vascular structures.
A morphologic finding indicating focal damage or loss of the podocytes in the renal tissue.
Localized widening of the lumen of the mammary ducts.
A finding indicating the presence of increased blood volume in the vascular lumen.
An extraskeletal osteosarcoma affecting the duodenum.
A tumor located underneath the adrenal capsule.
A morphologic and histochemical finding indicating depletion of mucin in the glands.
A morphologic finding indicating the presence of eosinophils within the mucosa.
Collection of fungal organisms in an anatomic site or medical device.
A cyst originating from the primitive foregut. It may arise from the upper aerodigestive tract, tracheobronchial tree, liver, and pancreas.
Architectural distortion of the tissue structure of a gland.
A morphologic finding indicating alteration of the shape/pattern of tissue components.
A morphologic finding indicating the partial or complete loss of a gland structure.
A term referring to cases of small lymphocytic lymphomas with an increased number of paraimmunoblasts or with signet-ring-like lymphocytes.
A morphologic finding indicating epithelial regrowth following injury.
An architectural morphologic finding indicating branching of glands as a result of a pathologic process.
Signs of chronic liver disease which include jaundice, ascites, palmar erythema, spider hemangiomas, gynecomastia, and encephalopathy.
A morphologic finding indicating the presence of a small population of cells in a tissue sample.
A morphologic finding indicating the presence of bony trabeculae rimmed with osteoblasts.
The pharmaceutically active ingredients of the concomitant medication.
An indication or description of any abnormal findings as a result of a physical examination.
An indication or description that an adverse event is continuing.
An indication or description that an adverse event is associated with or prolongs hospitalization.
An indication or description of an adverse event associated with a critical medical event.
An indication or description that the concomitant medication usage is ongoing.
An indication or description that a particular concomitant medication was taken in the past.
An indication of whether concomitant medication usage has occurred.
An indication or description that the subject will be continuing on to next phase of the trial.
An indication or description that the trial site has been unblinded in a blinded clinical trial.
An indication of whether protocol deviation has occurred.
An indication or description that an electrocardiogram assessment has occurred.
An indication or description that an exposure dosage was adjusted.
An indication or description that the course of study treatment has been carried out in full.
An indication of whether inclusion or exclusion criteria has been met.
An indication or description that the laboratory testing conditions laid out in the study protocol have been met.
An indication or description that a laboratory test has been performed.
An indication or description that an event or occurrence in an individual's medical history is being managed.
An indication or description that a medical history has been taken.
An indication or description that an event or occurrence in an individual's medical history is continuing.
An indication of whether a physical exam has been performed.
An indication or description that the seriousness of an adverse event was due to a congenital abnormality.
The outcome of the physical examination assessment.
Lobular neoplasia of the breast characterized by the presence of neoplastic cells with uniform nuclei.
Lobular neoplasia of the breast characterized by the presence of neoplastic cells with nuclei of various sizes and shapes.
A morphologic finding indicating the presence of a cellular population with a range of nuclear sizes and shapes.
A morphologic finding indicating the presence of cells with glycogen-rich cytoplasm.
A pleomorphic adenoma with increased cellularity.
A polyp that arises from the colon or rectum. It is characterized by the presence of serrated glands and the absence of generalized dysplasia. Some authors have suggested that it is a precursor lesion for some colorectal adenocarcinomas with microsatellite instability.
An immunophenotypic finding indicating positive membranous reactivity to a specific antibody.
An indication or description of the relationship of an adverse event to a non-study treatment.
An indication or description that an adverse event includes cancer.
An indication or description that an adverse event occurred with an overdose.
An indication or description regarding the use of a concomitant medication.
A laboratory test designed to quantify or qualify the poisonous nature of a sample.
An indication or description regarding an episode of substance usage.
A finding indicating the presence of protrusions or extensions in the basement membrane of the glomeruli.
A pharmacologic substance that does not directly kill cells, but instead affects cellular transport and metabolic functions to ultimately produce cell death.
A non-metastasizing tumor located underneath the adrenal capsule.
A metastasizing tumor located underneath the adrenal capsule.
A finding resulting from the examination of a tissue sample under light or electron microscopy.
A solution containing an attenuated, live culture preparation of the Bacillus Calmette Guerin (BCG) strain of Mycobacterium bovis with potential immunostimulating activity. Although the precise mechanism of action is unknown, upon intravesical administration, attenuated, live BCG bacteria in the solution come into direct contact with the bladder wall, inciting an antitumor granulomatous inflammatory reaction.
Accidental inhalation of a foreign material into the lungs.
A 4'-O-benzylated analogue of the anthracycline derivative doxorubicin, with potential antineoplastic activity. Berubicin intercalates into DNA and interrupts topoisomerase II activity, resulting in the inhibition of DNA replication and repair, as well as RNA and protein synthesis. Unlike other anthracycline derivatives, this agent crosses the blood-brain barrier (BBB) and can circumvent P glycoprotein/MRP1-mediated efflux.
A modified glutathione analogue and nitrogen mustard prodrug, with potential antineoplastic activity. Canfosfamide is selectively activated by glutathione S-transferase P1-1 into an alkylating metabolite that forms covalent linkages with nucleophilic centers in tumor cell DNA, which may induce a cellular stress response and cytotoxicity, and decrease tumor cell proliferation. Glutathione S-transferase P1-1 is an enzyme that is overexpressed in many human malignancies.
A second-generation, 32-amino acid peptide analogue of human amylin with antihyperglycemic activity. By mimicking amylin, davalintide, which has a half-life similar to amylin, slows gastric emptying, inhibits digestive secretions (gastric acid, pancreatic enzymes, and bile), reduces glucagon secretion, and increases satiety. These actions result in a decrease in blood glucose levels. Furthermore, davalintide exhibits high affinity binding to amylin, calcitonin and calcitonin-related peptide receptors. Compared to amylin, davalintide shows a prolonged duration of action due to its slowed receptor dissociation.
The acetate salt form of davalintde, a second-generation, 32-amino acid peptide analogue of human amylin with antihyperglycemic activity. By mimicking amylin, davalintide, which has a half-life similar to amylin, slows gastric emptying, inhibits digestive secretions (gastric acid, pancreatic enzymes, and bile), reduces glucagon secretion, and increases satiety. These actions results in a decrease in blood glucose levels. Furthermore, davalintide exhibits high affinity binding to amylin, calcitonin and calcitonin-related peptide receptors. Compared to amylin, davalintide shows a prolonged duration of action due to its slowed receptor dissociation.
A non-nucleoside polymerase inhibitor of the hepatitis C virus NS5B RNA-dependent RNA polymerase. Filibuvir binds to the non-catalytic Thumb 2 site on viral polymerase and causes a decrease in viral RNA synthesis.
The tromethamine salt form of prodrug fosbretabulin, a water-soluble phosphate derivative of a stilbenoid phenol derived from the African bush willow (Combretum caffrum) with antineoplastic activities. Upon administration, fosbretabulin is dephosphorylated to its active metabolite, combretastatin A4, which targets and binds to tubulin dimers and prevents microtubule polymerization, thereby resulting in mitotic arrest and apoptosis in endothelial cells. As apoptotic endothelial cells detach from their substrata, tumor blood vessels collapse; the acute disruption of tumor blood flow may result in tumor necrosis.
A sulfonamide derivative with antiulcerative activity.
A first generation sulfonylurea with antihyperglycemic activity. Heptolamide has never been marketed.
A thiazide derivative, also known as dihydrobenzthiazide, and carbonic anhydrase inhibitor, with antihypertensive activity.
A dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist, with hypoglycemic activity. Imiglitazar causes hepatotoxicity, and has never been marketed.
An analog of calcitriol and a vitamin D3 receptor (VDR) agonist, with potential antineoplastic activity. Upon administration, inecalcitol targets and binds to VDR. This activates VDR and VDR-mediated signal transduction pathways. This modulates the VDR-mediated expression of certain genes, including the expression of anti-cancer genes, enhances cellular differentiation, induces tumor cell apoptosis and inhibits tumor cell growth. VDR plays a central role in calcium homeostasis and in the growth of certain cancer cells.
An orally bioavailable thiazolidinedione and an agonist of peroxisome proliferator-activated receptor gamma (PPAR-gamma) with potential antineoplastic activity. Efatutazone binds to and activates PPAR-gamma thus inducing cell differentiation and apoptosis, leading to a reduction in cellular proliferation. PPAR-gamma is a nuclear hormone receptor and a ligand-activated transcription factor that controls the expression of genes involved in macromolecule metabolism and cell differentiation, specifically adipocyte differentiation.
A next-generation, pyrazole non-nucleoside reverse transcriptase inhibitor. Lersivirine retains activity against HIV viruses with mutations at position Y181, which confers resistance to efavirenz, etravirine, and nevirapine.
A small molecule inhibitor of microsomal triglyceride transfer protein (MTP), an enzyme located in the lumen of the endoplasmic reticulum responsible for absorbing dietary lipids and transferring triglycerides onto apolipoprotein B (apo-B) in the assembly of very-low-density lipoprotein. Inhibition of MTP by lomitapide blocks transfer of lipid to apo-B, and as a result emerging apo-B is destroyed and lipoprotein secretion is inhibited.
A methanesulfonic acid form of lomitapide, a small molecule inhibitor of microsomal triglyceride transfer protein.
Duplication of the T gene which plays an important role in notochord development. This genetic abnormality is implicated in the pathogenesis of familial chordoma.
The anhydrous form of the long-acting angiotensin-converting enzyme (ACE) inhibitor lisinopril with antihypertensive activity. Lisinopril, a synthetic peptide derivative, competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Lisinopril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A synthetic analogue of retinoic acid with differentiation inducing and potential antineoplastic activities. Like other retinoic acid agents, namirotene binds to and activates retinoic acid receptors (RARs), thereby altering the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.
A morpholinyl analogue of the anthracycline doxorubicin with antineoplastic activity. Nemorubicin is metabolized via the P450 CYP3A enzyme to a highly cytotoxic derivative. Unlike most anthracyclines, nemorubicin is a topoisomerase I inhibitor and appears to exert its effect through the nucleotide excision repair (NER) system. In addition, this agent does not show cross-resistance with other anthracyclines.
The hydrochloride salt form of nemorubicin, a morpholinyl analogue of the anthracycline doxorubicin with antineoplastic activity. Nemorubicin is metabolized via the P450 CYP3A enzyme to a highly cytotoxic derivative. Unlike most anthracyclines, nemorubicin is a topoisomerase I inhibitor and appears to exert its effect through the nucleotide excision repair (NER) system. In addition, this agent does not show cross-resistance with other anthracyclines.
Mutation of the fibroblast growth factor receptor 4 gene which is located on the long arm of chromosome 5. It has been described in patients with childhood rhabdomyosarcoma. Overexpression of this gene in these patients is associated with advanced stage disease and poor survival.
The potassium salt form of the bile acid taurocholic acid. Taurocholic acid is formed in the liver from cholesterol upon conjugation of cholic acid with taurine. Potassium taurocholate can be used to enhance the penetration and thus absorption of certain less lipophilic or hydrophilic substances through the skin or mucus membranes by increasing lipid solubilization.
Mutation of the Janus 2 kinase gene at chromosome 9. It is seen in most patients with polycythemia vera and less frequently in other myeloproliferative neoplasms.
A benign mesenchymoma arising from the kidney.
A group of rare myeloid and lymphoid neoplasms characterized by rearrangement of the PDGFRA, PDGFRB, or FGFR1 genes, resulting in the formation of fusion transcripts and aberrant tyrosine kinase activity. Eosinophilia is a characteristic finding but it is not always present. This group includes the myeloid and lymphoid neoplasms with t(8;9)(p22;p24.1);PCM1-JAK2 as a provisional entity.
Rearrangement of the PDGFRB gene, resulting in the formation of a fusion transcript and aberrant tyrosine kinase activity. It has been described in myeloid malignancies usually presenting as chronic myelomonocytic leukemia.
Rearrangement of the FGFR1 gene resulting in translocations with an 8p11 breakpoint. It has been described in hematologic malignancies presenting as myeloproliferative neoplasms or acute leukemias.
Hematologic neoplasms characterized by the rearrangement of the PDGFRA gene, most often resulting in the formation of FIP1L1-PDGFRA fusion transcripts. Patients usually present with chronic eosinophilic leukemia, and less often with acute myeloid leukemia or T-lymphoblastic leukemia.
Myeloid and rarely lymphoid neoplasms characterized by the rearrangement of the PDGFRB gene, most often resulting in the formation of ETV6-PDGFRB fusion transcripts. Patients usually present with chronic myelomonocytic leukemia and less often with atypical chronic myeloid leukemia, or chronic eosinophilic leukemia.
Hematologic neoplasms characterized by the rearrangement of the FGFR1 gene, resulting in translocations with an 8p11 breakpoint. Patients present with a myeloproliferative neoplasm, acute myeloid leukemia, lymphoblastic lymphoma/leukemia of T or B-cell lineage, or acute leukemia of mixed phenotype.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 19 in somatic cells.
A laboratory test result indicating the presence of an increased level of CA19-9 in the serum.
An astroblastoma characterized by the presence of high mitotic activity, cytologic atypia, and architectural distortion.
Inflammation of the anatomical structures of the middle ear secondary to an infectious process. Bacterial etiology is most common, but both viral and fungal pathogens are also possible. Symptoms include erythema and edema of the tympanic membrane, pain, and possibly fever. In severe infections, inflammation and edema of the structures of the middle ear can lead to perforation of the tympanic membrane secondary to the buildup of pressure in the narrow space.
An epithelioma characterized by the absence of keratin production.
A benign neoplasm arising from the yolk sac.
A non-neoplastic or neoplastic pathologic process affecting the leptomeninges of the brain.
A non-neoplastic or neoplastic pathologic process affecting the leptomeninges of the spinal cord.
The presence of brain metastasis that originates from a cancer growth in a distant anatomic site.
A symptom describing the inability to comprehend more than one element of a visual picture at a given moment, or to integrate the whole visual picture.
An aqueous oral rinse composed of an electrolyte solution supersaturated with phosphate and calcium ions with antimucositis and analgesic activities. This solution may help relieve mucositis and mucositis-induced pain by restoring the natural electrolyte and pH balance of human saliva and lubricating mucosal tissues of the mouth, tongue and oropharynx.
Reappearance of cholestasis caused by obstruction within the liver.
A congenital or acquired defect in the bile acid biosynthesis, resulting in progressive liver disease.
A spectrum of liver disorders that develop in patients with cystic fibrosis. It includes asymptomatic elevation of the liver function tests, steatosis, cholecystitis with cholelithiasis, sclerosing cholangitis, biliary cirrhosis, and cholangiocarcinoma.
Failure to perform hemodialysis due to blockage of the artery-vein grafts which provide the requisite vascular access.
Diabetes mellitus that develops during childhood.
A kidney disorder that appears during childhood.
Failure to achieve vascular access due to damage of the graft that was created for this purpose.
A disorder affecting the lungs due to asbestos exposure. Examples include asbestosis and lung carcinoma.
A congenital condition referring to defects of the course and structure of the coronary arteries.
A disorder affecting the smallest coronary arteries. Causes include atherosclerosis and arterial spasm. Chest pain is a frequently observed symptom.
A human monoclonal antibody against transmembrane glycoprotein non-metastatic melanoma protein B (GPNMB). Glembatumumab binds to GPNMB on cancer cells, but alone does not appear to inhibit cancer cell growth. However, this antibody could be utilized to deliver a conjugated cytotoxic agent to GPNMB-expressing tumor cells. GPNMB, overexpressed on the surface of various cancer cells, plays a key role in cancer cell proliferation.
Autosomal aneuploidy not associated with trisomy. It results in developmental malformations.
A very rare metabolic disorder characterized by an inborn error in the leucine degradation pathway. Patients excrete large amounts of beta-methyl-crotonylglycine in the urine.
Congenital deafness caused by mutations in the gene GJB2 (deafness gene).
A cancer vaccine containing dendritic cells (DCs) that are transfected with messenger RNA (mRNA) encoding human telomerase reverse transcriptase (hTERT) and survivin in addition to patient-specific melanoma-derived mRNA with potential immunostimulatory and antineoplastic activities. Upon administration, hTERT/survivin/melanoma tumor cell-derived mRNA-transfected dendritic cell vaccine may elicit a highly specific cytotoxic T-cell (CTL) response against melanoma cells expressing hTERT, survivin, and patient-specific melanoma-associated antigens. hTERT, the catalytic subunit of human telomerase, and survivin, a member of the inhibitor of apoptosis (IAP) family of proteins, may be upregulated in certain tumor cell types, playing key roles in tumor cell growth and survival.
A hereditary disorder of iron metabolism caused by mutations in the HFE gene. It is characterized by increased absorption of iron in the gastrointestinal mucosa. It results in abnormal iron accumulation in the liver, pancreas, skin, joints, heart, and testes. It may lead to skin pigmentation, liver failure, heart failure, and hypogonadism.
An orally bioavailable, synthetic, second-generation small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor MPC-3100 selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival; this agent may inhibit the growth and survival of a wide variety of cancer cell types. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability, and degradation of many oncogenic signaling proteins.
An agent targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR kinase inhibitor PF-04691502 inhibits both PI3K and mTOR kinases, which may result in apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K.
An intravenous formulation containing docetaxel, a semi-synthetic, second-generation taxane derived from a compound found in the European yew tree, Taxus baccata, with potential antineoplastic activity. Taxol analogue SID 530 binds to and stabilizes tubulin, inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase and cell death.
A neuroattenuated, replication-restricted, ICP34.5 deleted (RL1 gene)-mutant herpes simplex virus (HSV) type I, constructed from wild-type strain 17, with potential oncolytic activity. Upon intratumoral injection, oncolytic HSV1716 transfects, replicates in, and lyses rapidly dividing cells such as tumor cells. Because the RL1 gene is deleted, HSV1716 is unable to replicate in non-dividing cells.
An orally bioavailable small-molecule inhibitor of p21-activated kinase 4 (PAK4) with potential antineoplastic activity. PAK4 inhibitor PF-03758309 binds to PAK4, inhibiting PAK4 activity and cancer cell growth. PAK4, a serine/threonine kinase belonging to the p21-activated kinase (PAK) family, is often upregulated in a variety of cancer cell types and plays an important role in cancer cell motility, proliferation, and survival.
An oral rinse solution containing a strain of the bacteria Lactococcus lactis (L. lactis) genetically modified to express human Trefoil Factor 1 (hTFF1) with potential cytoprotective activity. With oral rinsing, human trefoil factor 1-secreting Lactococcus lactis AG013 may secrete and deliver hTFF1 to oral mucosal tissue, protecting or promoting the healing of damaged oral mucosa. hTFF1, a peptide belonging to the Trefoil factors family (TFF), is normally secreted by mucous epithelia and is involved in protecting mucosal tissue and maintaining mucosal surface integrity.
An water-in-oil (w/o) emulsion with immunomoadjuvant activity. Montanide ISA 51 VG appears to act by enhancing the immune system's cytotoxic T-lymphocyte (CTL) response against antigen(s) in vaccines. The surfactant mannide monooleate in Montanide ISA 51 VG contains vegetable-grade (VG) oleic acid derived from olive oil.
A cancer vaccine containing four HLA-A*0201-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Vaccine peptide epitopes are derived from the tumor associated antigens (TAAs) tyrosinase-related protein 2 (TRP2), glycoprotein 100 (gp100), Ephrin receptor A2 (EphA2) and human epidermal growth factor receptor 2 (HER2). Upon administration, HLA-A*0201-restricted TRp2-gp100-EphA2-HER2 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against TRP2-gp100-EphA2-HER2-expressing tumor cells, resulting in tumor cell lysis and decreased tumor cell proliferation. HLA-A*0201 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*0201 may improve antigenic peptide immunogenicity.
A dendritic cell (DC) vaccine containing ex vivo expanded autologous DCs obtained from a patient with leukemia with potential immunostimulating activity. Upon reintroduction into the host, the host dendritic cell vaccine-001 MSSM/BIIR may stimulate the immune system to mount a leukemia-specific cytotoxic T lymphocyte (CTL) response.
A small-molecule pan-Aurora kinase inhibitor with potential antineoplastic activity. Aurora kinase inhibitor TTP607 selectively binds to and inhibits Aurora kinases A, B and C, which may result in the disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cellular division and proliferation in Aurora kinase-overexpressing tumor cells. Aurora kinases A, B and C, are serine/threonine kinases that play essential roles in mitotic checkpoint control and are overexpressed by a wide variety of tumor cell types.
A lipoplexed formulation consisting of short-interfering RNAs (siRNAs) directed against protein kinase N3 (PKN3) encapsulated in catiogenic and fusiogenic lipids with potential antineoplastic activity. Upon administration, catiogenic and fusiogenic lipids promote anti-PKN3 siRNA Atu02 uptake by tumor cells; the siRNAs moieties are subsequently released once inside the cell. The siRNAs bind to PKN3 mRNAs, which may result in the inhibition of translation and expression of the PKN3 protein and, so, growth inhibition of tumor cells that overexpress PKN3. The protein kinase C-related molecule PKN3, downstream in the phosphoinositide-3-kinase (PI3K) signaling pathway, is upregulated in many tumor cells and plays an important role in invasive cell growth and metastasis.
A stable derivative of prostaglandin E2 (PGE2) with potential hematopoietic activity. Administration of 16,16 dimethyl-prostaglandin E2 (dmPGE2) appears to lead to increased formation of hematopoietic stem and progenitor cells. Even though the exact mechanism of action has yet to be fully elucidated, this agent may stimulate hematopoiesis by activating the Wnt signaling pathway, which increases cellular levels of beta-catenin, a subunit of the cadherin protein complex.
A non-camptothecin inhibitor of topoisomerase I with potential antineoplastic activity. Topoisomerase I inhibitor Genz-644282 binds to and inhibits the enzyme topoisomerase I, which may result in the inhibition of repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations.
A transdermal matrix patch formulation containing the synthetic opioid sufentanil with analgesic activity. Sufentanil binds to and activates the mu-opioid receptors in the central nervous system (CNS), thereby mimicking the effects of the endogenous opioids. Binding of sufentanil to opioid receptors stimulates exchange of GTP for GDP, inhibits adenylate cyclase, and decreases intracellular cAMP. This inhibits the release of various nociceptive neurotransmitters, such as substance P, gamma-aminobutyric acid (GABA), dopamine, acetylcholine, noradrenaline, vasopressin, and somatostatin. In addition, sufentanil closes N-type voltage-gated calcium channels and opens calcium-dependent inwardly rectifying potassium channels, which results in hyperpolarization of neuronal membranes and a reduction in neuronal excitability, and, subsequently, analgesia and sedation.
A cancer vaccine comprised of synthetic peptides derived from human melanoma antigen A1 (MAGE-A1), human melanoma antigen A3 (MAGE-A3) and cancer-testis antigen NY-ESO-1 with potential immunostimulating and antineoplastic activities. Upon administration, MAGE-A1/MAGE-A3/NY-ESO-1 peptides vaccine may stimulate the immune system to mount a cytotoxic T-cell (CTL) response against tumor cells expressing MAGE-A1, MAGE-A3 and NY-ESO-1, resulting in tumor cell lysis. The MAGE-A1, MAGE-A3, and NY-ESO-1 tumor-associated antigens (TAAS) are overexpressed by a variety of cancer cell types.
An antibody-drug conjugate (ADC) containing a fully human monoclonal antibody, directed against the extracellular domain of the human CD70 molecule, conjugated to a prodrug of a CC-1065 (rachelmycin) analogue via a stable peptide-based linker, with potential antineoplastic activity. The anti-CD70 antibody moiety of the anti-CD70 antibody-drug conjugate MDX-1203 selectively binds to the extracellular domain of CD70 on tumor cell surfaces. Upon internalization, the prodrug moiety is released and activated and binds to double-stranded B-DNA within the minor groove, thereby alkylating the -3 position of adenine, which may result in the inhibition of cellular proliferation of tumor cells that overexpress CD70. CD70, the ligand for the costimulatory receptor CD27 and a member of the tumor necrosis factor (TNF) family, is found on the surfaces of various types of cancer cells. The antitumor antibiotic CC-1065, a DNA minor-groove-binding alkylating agent, was originally isolated from the bacterium Streptomyces zelensis.
The hydrated, crystalline propionate ester (attached in position C-20) prodrug of camptothecin, an alkaloid isolated from the Chinese tree Camptotheca acuminata, with potential antineoplastic activity. Upon entry into cells, camptothecin-20(S)-O-propionate is hydrolyzed by esterases into the active form camptothecin. Camptothecin selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery, thus inhibiting DNA replication and triggering apoptotic cell death. Camptothecin readily undergoes hydrolysis at physiological pH, changing its conformation from the active, S-configured lactone structure to an inactive carboxylate form. The ester chain in the vicinity of the S-configured lactone moiety, a key determinant for the chemotherapeutic efficacy of the camptothecins, inhibits protein binding, rendering this agent resistant to hydrolysis and prolonging its half-life.
An orally bioavailable small-molecule inhibitor of MEK1 and MEK2 (MEK1/2) with potential antineoplastic activity. MEK inhibitor TAK-733 selectively binds to and inhibits the activity of MEK1/2, preventing the activation of MEK1/2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK1/2 (MAP2K1/K2) are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway and are often upregulated in a variety of tumor cell types.
A fusion protein consisting of a fully human monoclonal antibody directed against the endocytic dendritic cell (DC) receptor, DEC-205, linked to the tumor-associated antigen (TAA) NY-ESO-1 with potential immunostimulating and antineoplastic activities. The monoclonal antibody moiety of DEC-205/NY-ESO-1 fusion protein CDX-1401 binds to the endocytic DC receptor, which may result in DC endocytic internalization of this agent, specifically delivering the NY-ESO-1 moiety. DC processing of NY-ESO-1 may boost the immune system to mount a cytotoxic T-lymphocyte response (CTL) against cancer cells expressing NY-ESO-1. NY-ESO-1, a cell surface protein expressed in normal fetal and adult testes, is upregulated in a variety of tumor cell types.
A cancer vaccine consisting of a truncated recombinant HER2/neu peptide (dHER2) combined with the immunoadjuvant AS15 with potential immunostimulatory and antineoplastic activities. Upon administration, dHER2+AS15 vaccine may stimulate the host immune response to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells that overexpress the HER2/neu protein, resulting in tumor cell lysis. The tumor-associated antigen (TAA) HER2/neu is often overexpressed by a variety of tumor cell types; dHER2 includes amino acids 1-645 or 1-653 of the extracellular domain (ECD) and an immunogenic carboxyl terminal autophosphorylation portion of the intracellular domain (ICD). AS15 is an adjuvant formulation that contains the adjuvant systems AS01B and AS07A; AS01 B is composed of liposomes containing 3D-MPL and QS21 and AS07A is composed of the synthetic oligodeoxynucleotide (ODN) Toll-like receptor-9 (TLR9) agonist CpG 7909.
An orally bioavailable small-molecule inhibitor of the Hedgehog (Hh) signaling pathway with potential antineoplastic activity. Hedgehog inhibitor PF-04449913 appears to inhibit Hh pathway signaling. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair. Constitutive activation of Hh pathway signaling has been observed in various types of malignancies.
An orally bioavailable small-molecule inhibitor of MEK1 and MEK2 (MEK1/2) with potential antineoplastic activity. Pimasertib selectively binds to and inhibits the activity of MEK1/2, preventing the activation of MEK1/2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK1/2 (MAP2K1/K2) are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway and are often upregulated in a variety of tumor cell types.
The diphosphate prodrug of the stilbenoid combretastatin A1, originally isolated from the plant Combretum caffrum, with vascular-disrupting and antineoplastic activities. Upon administration, combretastatin A1 diphosphate (CA1P) is dephosphorylated to the active metabolite combretastatin A1 (CA1), which promotes rapid microtubule depolymerization; endothelial cell mitotic arrest and apoptosis, destruction of the tumor vasculature, disruption of tumor blood flow and tumor cell necrosis may ensue. In addition, orthoquinone intermediates, metabolized from combretastatin A1 by oxidative enzymes found to be elevated in some tumor types, may bind to tumor cell thiol-specific antioxidant proteins and DNA, and stimulate oxidative stress by enhancing superoxide/hydrogen peroxide production. CA1 binds to tubulin at the same site as colchicine but with higher affinity.
A ghrelin peptide analogue with potential anti-cachexia activity. Upon subcutaneous administration, ghrelin peptide analogue binds to and stimulates the G protein-coupled growth hormone secretagogue receptor (GHSR) in the central nervous system (CNS), thereby mimicking the appetite-stimulating and growth hormone-releasing effects of endogenous ghrelin. Stimulation of GHSR may also reduce the production of the pro-inflammatory cytokines TNF-alpha and interleukin-6, which may play direct roles in cancer-related loss of appetite. Ghrelin, naturally secreted by gastric endocrine cells, is a 28 amino acid peptide and an endogenous ligand for GHSR.
An orally bioavailable inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) tyrosine kinases with potential antineoplastic activity. IGF-1R/IR inhibitor KW-2450 selectively binds to and inhibits the activities of IGF-1R and IR, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-R1 and IR tyrosine kinases, overexpressed in a variety of human cancers, play significant roles in the stimulation of cellular proliferation, oncogenic transformation, and suppression of apoptosis.
A non-small cell lung cancer (NSCLC) vaccine containing modified mRNAs encoding cancer-testis antigen NY-ESO-1, melanoma-associated antigens C1 (MAGE-C1/CT7) and C2 (MAGE-C2/CT10), survivin, and the oncofetal antigen 5T4 with potential antitumor and immunomodulatory activities. Upon subcutaneous administration, non-small cell lung cancer mRNA-derived vaccine CV9201 may stimulate the immune system to mount a cytotoxic, antigen-specific T lymphocyte response (CTL) against NSCLC cells. The modified mRNAs in this vaccine are taken up by cells after injection and exhibit enhanced translational potency. The five tumor-associated antigens (TAAs) encoded by these mRNAs are frequently expressed by NSCLC cells.
A propylene glycol-free intravenous formulation containing the hydrochloride salt of the nitrogen mustard phenylalanine derivative melphalan complexed with polyanionic sulfobutyl ether beta-cyclodextrin (SBE-CD) with potential antineoplastic activity. Upon administration, melphalan is converted into highly reactive ethylenimmonium intermediates that induce covalent guanine N7-N7 intra- and inter-crosslinks and alkylation of adenine N3 of DNA; RNA and proteins may also be alkylated. Subsequently, RNA transcription and protein synthesis are inhibited, resulting in cell growth arrest. The addition of sulfobutyl ether beta-cyclodextrin to the formulation improves the solubility, stability and ease of use of melphalan; cyclodextrins are cyclic dextrins derived from starch.
A small-molecule prodrug of CEP-8983, a novel 4-methoxy-carbazole inhibitor of the nuclear enzymes poly(ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon administration and conversion from CEP-9722, CEP-8983 selectively binds to PARP 1 and 2, preventing repair of damaged DNA via base excision repair (BER). This agent enhances the accumulation of DNA strand breaks and promotes genomic instability and apoptosis. CEP-8983 may potentiate the cytotoxicity of DNA-damaging agents and reverse tumor cell chemo- and radioresistance. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and can be activated by single strand breaks in DNA.
A morphologic finding indicating the presence of clusters of capillaries projecting into a dysplastic bronchial epithelium. It is considered a pre-invasive lesion.
A rare syndrome characterized by deficiency of specific antibodies to polysaccharide antigens while the specific antibodies to protein antigens are normal.
Rare syndromes caused by chromosomal defects and characterized by the presence of multiple X chromosomes and one Y chromosome. Signs and symptoms include short stature, mental retardation, hypogonadism, undescended testes, gynecomastia, and hypotonia.
One of the possible results of an adverse event outcome where the subject recuperated and is free of any pathological conditions resulting from the prior disease or injury.
An orally bioavailable inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1, 2 and 3 with potential antiangiogenic and antineoplastic activities. Tivozanib binds to and inhibits VEGFRs 1, 2 and 3, which may result in the inhibition of endothelial cell migration and proliferation, inhibition of tumor angiogenesis and tumor cell death. VEGFR tyrosine kinases, frequently overexpressed by a variety of tumor cell types, play a key role in angiogenesis.
A cancer vaccine consisting of autologous dendritic cells (DCs) loaded with CD133-positive autologous brain tumor stem cells (BTSCs) -derived mRNA with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, autologous CD133-positive BTSC mRNA-pulsed autologous dendritic cell vaccine may elicit a cytotoxic T-lymphocyte (CTL) response against the CD133-positive BTSCs from which the autologous tumor mRNA is derived. CD133, a tumor-associated antigen (TAA) and neural stem cell marker, has been found on a specific subset of glioblastoma multiforme (GBM) stem cells; its presence has been correlated with resistance to conventional chemotherapy and radiotherapy.
A tri-Fab bispecific monoclonal antibody (BiMoAb) divalent for the carcinoembryonic antigen (CEA) and monovalent for histamine-succinyl-glycine (HSG) peptide-hapten radiolabeled with iodine I 131 (I131) with antigen-binding and radioisotopic activities. Iodine I 131-labeled anti-CEA/anti-HSG bispecific monoclonal antibody TF2 binds to the tumor-associated antigen (TAA) CEA on CEA-expressing tumor cells; these cells may then be radioimaged scintigraphically.
A recombinant, soluble glycosylated form of human angiotensin converting enzyme 2 (rhACE2) with antihypertensive and potential antineoplastic activities. Recombinant human angiotensin converting enzyme 2 APN01 may normalize ACE2 levels, cleaving angiotensin II to create angiotensin-(1-7) and restoring the function of the renin-angiotensin system (RAS). ACE2, a homolog of ACE1, appears to function as a negative regulator of the RAS system by converting angiotensin II to angiotensin-(1-7), a peptide with actions that counteract the cardiovascular actions of angiotensin II. In addition, angiotensin-(1-7) may inhibit cyclooxygenase 2 (COX-2) and the production of proinflammatory prostaglandins and may activate the angiotensin-(1-7) G protein-coupled receptor Mas, resulting in diminished tumor cell proliferation. ACE2 levels may be reduced in malignancy and diabetes and in liver, cardiovascular and lung diseases.
An orally bioavailable indole-3-carbinol (I3C) analogue inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic and antiangiogenic activities. Akt inhibitor SR13668 binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation, and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
A radiopharmaceutical consisting of a sulfonamide covalently attached to the positron-emitting isotope fluorine F 18 with CA-IX-binding and radioisotopic activities. Upon administration, the sulfonamide moiety of [F18]VM4-037 binds to the cell-surface tumor-associated antigen (TAA) carbonic anhydrase IX isoenzyme (CA-IX); CA-IX-expressing tumor cells can then be visualized using positron emission tomography (PET). CA-IX has been found to be elevated in a variety of hypoxic tumors; elevated CA-IX has been positively correlated with tumor growth, tumor invasion and poor prognosis.
A cell-based cancer vaccine consisting of hybrid cells created by electrofusing autologous dendritic cells (DCs) and autologous lymphoma cells with potential immunostimulating and antitumor activities. Upon administration, autologous lymphoma cell/autologous dendritic cell electrofusion hybrid vaccine may stimulate the immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against specific autologous lymphoma-associated antigens, resulting in lymphoma cell apoptosis.
A cell-based cancer vaccine consisting of hybrid cells created by electrofusing allogeneic dendritic cells (DCs) and autologous lymphoma cells with potential immunostimulating and antitumor activities. Upon administration, autologous lymphoma cell/allogeneic dendritic cell electrofusion hybrid vaccine may stimulate the immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against specific autologous lymphoma-associated antigens, resulting in lymphoma cell apoptosis.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysate from autologous lymphoma cells with potential immunostimulatory and antineoplastic activities. Upon intranodal administration, autologous lymphoma cell lysate-pulsed autologous DC vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against lymphoma cells, which may result in lymphoma cell lysis.
A fully human, IgG1 monoclonal antibody directed against the FLT3 tyrosine kinase receptor (CD135) with potential antineoplastic activity. Upon binding to FLT3, anti-FLT3 monoclonal antibody IMC-EB10 blocks FLT3 ligand binding to FLT3 and subsequent FLT3 phosphorylation, which may result in the inhibition of FLT3-mediated signal transduction pathways. In addition, this agent may stimulate an anti-FLT3 antibody-dependent cell-mediated cytotoxicity (ADCC) against FLT3-expressing tumor cells, which may result in the inhibition of cellular proliferation and survival in FLT3-expressing cells. FLT3 (FLK2), a class III tyrosine kinase receptor, is overexpressed or mutated in most B lineage and acute myeloid leukemias.
A cancer vaccine containing four HLA-A*2402-restricted peptide epitopes with potential immunostimulatory and antitumor activities. The peptide epitopes are derived from URLC10 (up-regulated lung cancer 10); CDCA1 (cell division associated 1); and vascular endothelial growth factor receptors (VEGFRs) 1 and 2. Upon administration, HLA-A*2402-restricted URLC10-CDCA1-VEGFR1-VEGFR2 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against URL10-, CDCA1-, VEGFR1- and VEGFR2-expressing tumor cells, resulting in tumor cell lysis and decreased tumor cell proliferation. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A cancer vaccine consisting of autologous renal cell carcinoma (RCC) tumor cells modified with the hapten 2,4-dinitrophenol (DNP) with potential immunostimulating and antineoplastic activities. Administration of DNP-modified autologous renal cell carcinoma tumor cell vaccine may induce a cytotoxic T-lymphocyte (CTL) response against renal cell carcinoma tumor cells. DNP conjugation may enhance the immunogenicity of weakly immunogenic antigens.
An orally bioavailable tartrate salt of vinorelbine, a semisynthetic vinca alkaloid with potential antineoplastic activity. Vinorelbine binds to tubulin, thereby inhibiting tubulin polymerization into microtubules and spindle formation and resulting in apoptosis of susceptible cancer cells. Inhibition of mitotic microtubules correlates with antitumor activity, whereas inhibition of axonal microtubules seems to correlate with vinorelbine's neurotoxicity. Compared to related vinca alkaloids, vinorelbine is more selective against mitotic than axonal microtubules in vitro, which may account for its decreased neurotoxicity. This agent is also a radiation-sensitizing agent.
A synthetic Arg-Gly-Asp (RGD)-containing cyclic peptide radiolabeled with technetium Tc 99m with integrin-binding and radioisotopic activities. Upon administration, technectium Tc 99m-NC100692 binds to alpha5beta3 integrin and to a lesser extent alpha5beta5; subsequently, alpha5beta3-expressing tumor cells can be visualized using scintigraphy and the degree of tumor angiogenesis can be determined. Integrins, membrane-spanning protein receptors, may be upregulated on proliferating endothelial cells; their overexpression has been associated with neovascularization, differentiation, proliferation of tumor cells and poor prognosis.
A preparation of transforming growth factor-beta (TGF-beta)-resistant Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs) directed to EBV through their native receptor and HER2 through a retrovirally transduced HER2 chimeric antigen receptor (CAR) with potential antineoplastic activity. Autologous EBV-specific CTLs are produced by exposing autologous CTLs to ""stimulator"" autologous EBV-transformed lymphoblastoid cell lines (EBV-LCLs). Subsequently, autologous EBV-specific CTLs are transduced with retroviral vectors expressing the mutant type II TGF-beta dominant-negative receptor (DNR), which blocks signaling by all three TGF-beta isoforms, and the HER2 CAR. After transduction, transgenic EBV-CTLs are expanded on EBV-LCLs. Upon administration, autologous HER2 chimeric receptor/TGFbeta dominant negative receptor-expressing EBV-specific cytotoxic T lymphocytes may bind to HER2-expressing tumors cells, which may result in CTL-mediated cell lysis and inhibition of tumor cell proliferation. Tumor-expressed TGF-beta inhibits T lymphocyte activation and expansion.
The sodium salt of silmitasertib, an orally bioavailable small-molecule inhibitor of CK2 with potential antineoplastic activity. Silmitasertib selectively binds to and inhibits the enzyme casein kinase II (CK2), which may lead to an inhibition of cellular proliferation. CK2, a protein kinase often overexpressed in a variety of cancer cell types, appears to be correlated with malignant transformation, tumor growth and survival.
A peptide-based cancer vaccine, containing amino acid residues 27 through 35 of T cell receptor gamma alternate reading frame protein (TARP), with potential immunostimulatory and antineoplastic activities. Upon administration, TARP 27-35 peptide vaccine may stimulate a host cytotoxic T-cell (CTL) response against TARP-expressing tumor cells, resulting in tumor cell cytotoxicity. The nuclear protein TARP is commonly expressed on prostate and breast cancer cells and is highly immunogenic.
A peptide-based cancer vaccine, consisting of amino acid residues 29 through 37 of T cell receptor gamma alternate reading frame protein (TARP) with a leucine-to-valine substitution at position 9, with potential immunostimulatory and antineoplastic activities. Upon administration, TARP 29-37-9V peptide vaccine may induce a cytotoxic T-lymphocyte (CTL) response against TARP-expressing tumor cells, which may result in decreased tumor cell proliferation. The leucine-to-valine substitution at position 9 of this peptide improves its immunogenicity. The nuclear protein TARP is commonly expressed on prostate and breast cancer cells and is highly immunogenic.
A peptide vaccine derived from the synthetic peptide pyroEHWSYGLRPG, corresponding to amino acids 22-31 of mouse gonadotropin releasing hormone (GnRH), with potential immunocastration activity. PEP223 is dimerized and contains a D-lysine (k) substitution at position 6 (pyroEHWSYkLRPG) to increase its immunogenicity. Anti-GnRH vaccine PEP223 may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against GnRH, neutralizing its activity. In turn, testosterone production and tumor cell growth may be inhibited in testosterone-sensitive tumors.
A methylated derivative and structural analog of PRIMA-1 (p53 re-activation and induction of massive apoptosis), with potential antineoplastic activity. Upon administration, PRIMA-1 analog APR-246 covalently modifies the core domain of mutated forms of cellular tumor antigen p53 (p53) through the alkylation of thiol groups. These modifications restore both the wild-type conformation and function to mutant p53, which reconstitutes endogenous p53 activity, leading to cell cycle arrest and apoptosis in tumor cells. This agent may work synergistically with other antineoplastic agents. p53, a tumor suppressor and transcription factor normally activated upon DNA damage, is frequently mutated and overexpressed in cancer cells; it plays a key role in both DNA repair and the induction of apoptosis.
A population of activated, immortalized, interleukin-2 (IL-2)-dependent, cytotoxic natural killer (NK) cells with potential antitumor activity. Natural killer cells ZRx101 are derived from NK-92 cells, having been modified to target tumor-associated antigens (TAAs) upregulated in certain types of cancer. The NK-92 cell line was originally isolated from a patient with large granular lymphocytic (LGL) leukemia/lymphoma.
The orally bioavailable fumarate salt of formoterol, a long-acting, selective beta2-adrenergic receptor agonist with bronchodilating and potential anti-cachexia and anabolic activities. In addition to formoterol's bronchodilating activity, formoterol exhibits anti-cachexia activity through the inhibition of the ATP-ubiquitin-dependent proteolytic system, which may result in a decrease in protein degradation and muscle cell apoptosis. In addition, formoterol may also increase insulin-like growth factor (IGF) signaling, resulting in an increase in protein synthesis. This agent may also inhibit the calcium-dependent calpain system, resulting in the inhibition of muscle wasting.
A cell-based cancer vaccine comprised of autologous dendritic cells pulsed with multiple antigenic peptides derived from T-cell receptor gamma-chain alternate reading frame protein (TARP), with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, multi-epitope (ME) TARP-pulsed autologous dendritic cell vaccine may stimulate anti-tumor cytotoxic T-lymphocyte (CTL) and antibody responses against TARP-expressing cancer cells, resulting in tumor cell lysis. The highly immunogenic nuclear protein TARP is expressed in a variety of cancer cell types.
An injectable ultrasound contrast media formulation composed of microbubbles of stabilized sulphur hexafluoride (SF6) in sodium chloride solution. With stabilized sulphur hexafluoride microbubble-based contrast agent, ultrasound waves are scattered and reflected at the microbubble-blood interface during ultrasound imaging, thereby enhancing blood vessel visualization and the contrast between blood vessels and adjacent tissues.
A radioconjugate containing the acetate salt of eribulin, labeled with the beta particle-emitting radioisotope carbon C 14, with radioisotopic and potential antineoplastic activities. Upon administration, eribulin binds to the vinca domain of tubulin and inhibits the polymerization of tubulin and the assembly of microtubules, resulting in inhibition of mitotic spindle assembly, induction of cell cycle arrest at G2/M phase, and, potentially, tumor regression. The radioisotope moiety of this agent acts as a radioactive tracer.
An orally bioavailable aqueous solution containing the chloride salt of the radioisotope calcium-41 (41Ca) with phosphate-binding and radioisotopic activities. Upon administration of calcium-41 chloride aqueous solution, calcium-41 is preferentially taken up by osteoblasts, which generate mineralized osteoid containing calcium. Calcium-41 accumulation and turnover in bone can be measured with bone scintigraphy and urinary isotope excretion.
An orally bioavailable aqueous solution containing the chloride salt of the radioisotope calcium-46 (46Ca) with phosphate-binding and radioisotopic activities. Upon administration of calcium-46 chloride aqueous solution, calcium-46 is preferentially taken up by osteoblasts, which generate mineralized osteoid containing calcium. Calcium-46 accumulation and turnover in bone can be measured with bone scintigraphy and urinary isotope excretion testing.
A chimeric monoclonal antibody directed against the antigen GC182 with potential immunostimulatory and antineoplastic activities. Upon administration, claudiximab specifically binds to GC128, which may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against GC182-expressing tumor cells, resulting in decreased tumor cell proliferation. The CD20-like antigen GC182, a gastric differentiation protein, is often overexpressed on the cell surfaces of a variety of tumor cells, including gastric, pancreatic, esophageal cancer and non-small cell lung cancer (NSCLC) cells.
A nanoparticle-based prodrug formulation consisting of polymeric micelles incorporating the inorganic platinum agent cisplatin with potential antineoplastic activity. In micellar nanoparticle-encapsulated cisplatin NC-6004, cisplatin forms a polymer-metal complex with hydrophilic polyethylene glycol poly(glutamic acid) block copolymers by attaching to the micelle inner core consisting of the hydrophobic polyamino acids. Upon cell entry and release from the polymer-metal complex, cisplatin forms highly reactive, charged platinum complexes that bind to nucleophilic groups such as GC-rich sites in DNA, inducing intrastrand and interstrand DNA cross-linking, DNA-protein cross-linking and, subsequently, tumor cell apoptosis and growth inhibition. Due to the hydrophilic nature of polyethylene glycol, this formulation increases the water-solubility of cisplatin and decreases the nephrotoxicity and neurotoxicity associated with the administration of cisplatin alone.
A monoclonal antibody directed against the human alpha5beta1 integrin with potential antiangiogenic and antineoplastic activities. Anti-alpha5beta1 integrin monoclonal antibody PF-04605412 selectively binds to alpha5beta1 integrin, preventing the binding of integrin ligands. This may result in the inhibition of endothelial cell-cell interactions, endothelial cell-matrix interactions, and integrin-mediated tumor angiogenesis and metastasis in alpha5beta1-expressing tumor cells. Alpha5beta1 integrin, a cell adhesion and signaling receptor, is often overexpressed on the surface of tumor vessel endothelial cells and plays a crucial role in endothelial cell adhesion and migration.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with renal cell carcinoma (RCC) tumor cell lysate containing tumor associated antigens (TAAs) with potential immunostimulatory and antineoplastic activities. Upon administration, autologous renal cell carcinoma tumor lysate-dendritic cell vaccine may stimulate anti-tumoral cytotoxic T-lymphocyte (CTL) and antibody responses against RCC tumor cells expressing RCC TAAs, resulting in RCC tumor cell lysis.
A water-soluble, amphipathic, 28 amino acid (amino acids 50-77), 2.9 kD fragment peptide (p28) derived from the protein azurin with potential antineoplastic and antiangiogenic activities. Although the mechanism has yet to be fully elucidated, the preferential cellular uptake of azurin-derived cell-penetrating peptide p28 by tumor cells and endothelial cells is likely via caveolae-mediated endocytosis; the C-terminal 18 amino acid residues (50-67) appear to be responsible for this preferential uptake. After cell entry, the first 12 amino acid residues interact with tumor suppressor p53 and form a p28:p53 complex, which may result in a reduction of proteasomal degradation of p53, increased p53 levels, and p53-mediated cell cycle inhibition and apoptosis. Azurin is a cupredoxin secreted by the bacterium Pseudomonas aeruginosa. Cell penetrating peptides (CPPs) are cationic and/or amphipathic peptides, typically less than 30 amino acids in length, that can penetrate cell membranes easily and may transport molecular cargo.
A depot formulation containing a bioresorbable, controlled-release, calcium sulphate-based paste of the nonsteroidal antiandrogen 2-hydroxyflutamide (2-HOF) with potential antineoplastic activity. Upon injection into the tumor site in the prostate, 2-hydroxyflutamide depot slowly releases 2-HOF, which competitively binds to androgen receptors (ARs), blocking the binding of dihydrotestosterone (DHT). This may inhibit androgen-dependent DNA and protein synthesis, resulting in tumor cell growth arrest and decreased cellular proliferation. In addition, 2-HOF inhibits nuclear uptake of androgen in androgen-responsive tissues.
A transdermal matrix patch containing the synthetic opioid buprenorphine with analgesic and sedative activities. Buprenorphine binds to and activates the mu-opioid receptors in the central nervous system (CNS), thereby mimicking the effects of the endogenous opiates. Binding to opioid receptors stimulates exchange of GTP for GDP, inhibits adenylate cyclase, and decreases intracellular cAMP. This inhibits the release of various nociceptive neurotransmitters, such as substance P, gamma-aminobutyric acid (GABA), dopamine, acetylcholine, noradrenaline, vasopressin, and somatostatin. In addition, buprenorphine closes N-type voltage-gated calcium channels and opens calcium-dependent inwardly rectifying potassium channels, resulting in hyperpolarization, reduced neuronal excitability, analgesia and sedation. Buprenorphine is a partial agonist at the mu-opioid receptor and an antagonist at the kappa-opioid receptor in the CNS.
A bispecific monoclonal antibody directed against the human epidermal growth factor receptors ErbB2 (Her2) and ErbB3 (Her3) with potential antineoplastic activity. The anti-ErB2 targeting arm of anti-ErbB2/anti-ErbB3 bispecific monoclonal antibody MM-111 binds to ErbB2 on tumor cells with high affinity while the anti-Erb3 therapeutic arm binds to ErbB3, which may result in the inhibition of cellular proliferation and differentiation in ErbB2-overexpressing tumor cells via inhibition of ErbB3-dependent signal transduction pathways. ErbB2 and ErB3 are members of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases and are frequently overexpressed in solid tumors.
An indication of whether a medical history has been taken.
A finding of greater than 90 bacilli per 250x field.
Stage IA includes: T1, N0, M0. T1: Tumor 20 mm or less in greatest dimension. T1 includes T1mi. T1mi: Tumor 1 mm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 7th Ed.)
Stage IB includes: (T0, N1mi, M0); (T1, N1mi, M0). T0: No evidence of primary tumor. T1: Tumor 20 mm or less in greatest dimension. T1 includes T1mi. T1mi: Tumor 1 mm or less in greatest dimension. N1mi: Nodal micrometastases. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 7th Ed.)
An inherited disorder affecting mostly males. It results from defective genes that are present on the X chromosome.
Stage 0 includes: Tis, N0, M0. Tis: In situ primary tumor. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IA includes: T1, pN0, M0. T1: Primary tumor equal or less than 2 cm in size. pN0: No regional lymph node metastasis by pathologic examination. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IB includes: T1, cN0, M0. T1: Primary tumor equal or less than 2 cm in size. cN0: No regional lymph node metastasis by clinical examination. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IIA includes: T2/T3, pN0, M0. T2: Primary tumor greater than 2 cm but not more than 5 cm in maximum dimension. T3: Primary tumor over 5 cm in maximum dimension. pN0: No regional lymph node metastasis by pathologic examination. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IIB includes: T2/T3, cN0, M0. T2: Primary tumor greater than 2 cm but not more than 5 cm in maximum dimension. T3: Primary tumor over 5 cm in maximum dimension. cN0: No regional lymph node metastasis by clinical examination. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IIC includes: T4, N0, M0. T4: Primary tumor invades bone, muscle, fascia, or cartilage. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IIIA includes: Any T, N1a, M0. N1a: Micrometastasis in regional lymph nodes. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IIIB includes: Any T, N1b/N2, M0. N1b: Macrometastasis in regional lymph nodes. N2: In transit metastasis. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IV includes: Any T, Any N, M1. M1: Metastasis beyond regional lymph nodes. (AJCC 7th Ed.)
Stage IA includes: T1a, N0, M0. T1a: Cutaneous melanoma with a tumor measuring 1.0 mm or less in thickness, without ulceration and with mitosis less than 1/mm2. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 7th Ed.)
Stage IB includes: (T1b, N0, M0); (T2a, N0, M0). T1b: Cutaneous melanoma with a tumor measuring 1.0 mm or less in thickness, with ulceration or mitoses equal or more than 1/mm2. T2a: Cutaneous melanoma with a tumor measuring 1.01-2.0 mm in thickness, without ulceration. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 7th Ed.)
Stage IIA includes: (T2b, N0, M0); (T3a, N0, M0). T2b: Cutaneous melanoma with a tumor measuring 1.01-2.0 mm in thickness, with ulceration. T3a: Cutaneous melanoma with a tumor measuring 2.01-4.0 mm in thickness, without ulceration. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 6th and 7th Eds.)
Stage IIC includes: T4b, N0, M0. T4b: Cutaneous melanoma with a tumor measuring more than 4.0 mm in thickness, with ulceration. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 6th and 7th Eds.)
Stage IIIA includes: (T1-4a, N1a, M0); (T1-4a, N2a, M0). T1-4a: Non-ulcerated cutaneous melanoma of any thickness. N1a: Cutaneous melanoma with micrometastasis in one regional lymph node. N2a: Cutaneous melanoma with micrometastases in 2-3 regional lymph nodes. M0: No detectable evidence of distant metastases. (from AJCC 7th Ed.)
Stage IIIB includes: (T1-4b, N1a, M0); (T1-4b, N2a, M0); (T1-4a, N1b, M0); (T1-4a, N2b, M0); (T1-4a, N2c, M0). T1-4b: Ulcerated cutaneous melanoma of any thickness. T1-4a: Non-ulcerated cutaneous melanoma of any thickness. N1a: Cutaneous melanoma with micrometastasis in one regional lymph node. N2a: Cutaneous melanoma with micrometastases in 2-3 regional lymph nodes. N1b: Cutaneous melanoma with macrometastasis in one regional lymph node. N2b: Cutaneous melanoma with macrometastases in 2-3 regional lymph nodes. N2c: Cutaneous melanoma with intralymphatic metastases (in transit or satellite metastases) without metastatic nodes. M0: No detectable evidence of distant metastases. (from AJCC 7th Ed.)
Stage IIIC includes: (T1-4b, N1b, M0); (T1-4b, N2b, M0); (T1-4b, N2c, M0); (Any T, N3, M0). T1-4b: Ulcerated cutaneous melanoma of any thickness. N1b: Cutaneous melanoma with macrometastasis in one regional lymph node. N2b: Cutaneous melanoma with macrometastases in 2-3 regional lymph nodes. N2c: Cutaneous melanoma with intralymphatic metastases (in transit or satellite metastases) without metastatic nodes. N3: Cutaneous melanoma with 4 or more metastatic nodes, or matted nodes, or in transit met(s)/satellite(s) with metastatic node(s). M0: No detectable evidence of distant metastases. (from AJCC 7th Ed.)
An image of inferior quality, may still be adequate to make a diagnosis.
An artifact that occurs when the scanned body part is larger than field of view (FOV) such that portions of the object outside of the desired FOV get mapped to an incorrect location inside the FOV.
An artifact that occurs when tissues in another plane get added to the image.
An artifact that occurs when tissues outside the field of view (FOV) get added to the opposite side of the image.
An artifact that occurs when signals from a different spectral range get added to an image.
An artifact resulting from an error in data collection.
Criteria for the diagnosis of Alzheimer's disease (AD), proposed in 1984 by the National Institute of Neurological and Communicative Disorders (NINCDS) and the Stroke-Alzheimer's Disease and Related Disorders Association (ADRDA, now the Alzheimer's Association). The criteria state that existing cognitive impairment may be considered possible or probable AD by neuropsychological testing but definitive diagnosis requires histopathologic confirmation. They specify eight cognitive domains that may be impaired in AD: memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving, and functional abilities.
An artifact that occurs where different tissues meet.
An edge artifact that results in image blurring.
An artifact that happens when a structure is present in adjacent slices and their signals are averaged.
A magnetic field perturbation artifact that results in multiple high intensity rings.
An artifact resulting from movement of the object being imaged during the imaging sequence.
An artifact that results from turbulent flow of body fluids in an imaging field.
An artifact that results from a gradient which is not constant with respect to the gradient direction.
An artifact resulting from the flow of unsaturated spins into the imaged slice.
An artifact resulting from the flow of excited spins out of the imaged slice.
An artifact resulting from non-uniform signal intensities across the imaging field.
An artifact resulting from a signal which has a frequency different from that expected for the system.
An artifact resulting in ghost images of a vessel extending across the image in the phase encoding direction.
An artifact often associated with cardiac imaging where the algorithm which provides the best temporal resolution for each slice can provides suboptimal image quality for the entire volume since the cardiac temporal resolution changes from slice to slice.
Artifacts that are produced when acquisition times are reduced and some signals are computed rather than acquired.
A characteristic artifact (ghost) which is shifted with respect to the main image by a half-field of view, resulting from a mismatch in either the amplitude or phase between odd and even echoes.
Stage IIIA includes: (T1/T2, N1a/N1b, M0); T1: Invasive vulvar cancer confined to the vulva or perineum. T2: Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement). N1a: Vulvar cancer with one or two lymph node metastasis each measuring 5 mm or less. N1b: Vulvar cancer with one lymph node metastasis measuring 5 mm or greater. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: (T1/T2, N2a/N2b, M0). T1: Invasive vulvar cancer confined to the vulva or perineum. T2: Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement). N2a: Vulvar cancer with three or more lymph node metastases each measuring 5 mm or less. N2b: Vulvar cancer with two or more lymph node metastases measuring 5 mm or greater. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIC includes: (T1/T2, N2c, M0). T1: Invasive vulvar cancer confined to the vulva or perineum. T2: Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement). N2c: Vulvar cancer with lymph node metastasis with extracapsular spread. M0: No distant metastasis. (AJCC 7th ed.)
An artifact that appears as stripes within the image.
An artifact resulting from static and dynamic field changes in a scanner magnetic field.
An imaging artifact caused by a metal structure present in the scan field.
A shape distortion in the z-axis resulting from the weighting function used in the helical interpolation algorithm.
An artifact that occurs as the number of sections acquired per rotation increases and the x-ray beam becomes cone-shaped rather than fan-shaped.
An artifact that appears as a point to point signal fluctuation in a uniform material.
An artifact resulting from scatter of the beam by a dense object.
An artifact resulting from absorpsion of lower energy photons as the beam penetrates through a tissue.
An artifact that is due to a group of channels or views that deviate gradually from the true measurement.
An artifact that is due to errors in an individual detector calibration.
An artifact resulting from an inconsistency in a single measurement.
An artifact resulting from data processing steps after capture of an image.
An artifact resulting from the leakage of an imaging agent from its location of administration.
An artifact that results when an imaging agent is not absorbed or metabolized at the expected rate.
An artifact resulting from excess signal at the injection site.
An artifact resulting from the contamination of the imaging field with an extraneous body substance.
Artifacts that result when the grid frequency is too low or when the grid orientation is parallel to the scan direction.
An artifact resulting from factors within the object being imaged.
An artifact resulting from the presence of a foreign body between the target and the receiver.
An artifact resulting from a problem with the patient.
An artifact resulting from the specific anatomy of the patient.
Artifacts related to the physique or body build of the patient.
An artifact resulting from a patient with a large body size or body mass.
An artifact resulting from the presence of another body structure between the target and the receiver.
An artifact resulting from the incorrect positioning of the patient.
An image artifact that results in unexpected signals due to patient physiology or problem metabolizing an imaging agent.
An imaging artifact resulting from a patient arrhythmia.
An imaging artifact resulting from hyperglycemia of the patient.
An artifact resulting from movement of the patient during image capture.
An artifact resulting from the use of defective equipment or from improper use of equipment.
Artifacts resulting from the electronics of the plate reader or from issues associated with the image plate.
An image of reduced quality resulting from the application of the wrong mask.
An image of reduced quality resulting from the application of a mask in the wrong way.
An image of reduced quality resulting from the application of too many masks.
An image of reduced quality resulting from the application of too few masks.
An image of reduced quality resulting from the use of incorrect or incomplete instructions.
An image of reduced quality resulting from the use of instructions with missing steps.
An image of reduced quality resulting from the use of the wrong instructions.
An image of reduced quality due to the collection or rejection of the wrong signal frequencies.
A squamous cell carcinoma associated with human papilloma type 16 virus, arising from the oropharynx.
The result obtained from a test commonly administered to assess the physiologic response to extending the arms as straight as possible alongside the body when lying down.
Blue- or purplish-colored body; this is caused by excessive amounts of deoxygenated hemoglobin in the skin vessels of the body.
Blue- or purplish-colored limbs; this is caused by excessive amounts of deoxygenated hemoglobin in the skin vessels of the limbs.
A symptom of gastrointestinal dysfunction seen in neonates who have been exposed to drugs during pregnancy; often accompanied by excessive sucking of fists, fingers and thumbs.
During examination of the newborn infant, the examiner looks for symmetric movement of the lip corners. Movement of the lip corners is governed by the zygomatic major muscle.
Signs and symptoms associated with disturbances within the central nervous system, which includes the brain, spinal cord and meninges.
Shallow inhalations and exhalations that indicate respiratory distress.
Stage IIIC includes: T1-T3, N1, M0. T1: Tumor limited to the uterus. T2: Tumor extends beyond the uterus, within the pelvis. T3: Tumor infiltrates abdominal tissues. N1: Regional lymph node metastasis. M0: No distant metastasis. This staging applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (AJCC 7th ed.)
Stage I includes: (T1, M0, Risk factors: unknown); IA (T1, M0, Risk factors: low risk); IB (T1, M0, Risk factors: high risk). T1: Tumor confined to uterus. M0: No distant metastasis. (AJCC 7th ed.)
Stage IA includes: T1, M0, Risk factors: low risk. T1: Tumor confined to uterus. M0: No distant metastasis. (AJCC 7th ed.)
Stage IB includes: T1, M0, Risk factors: high risk. T1: Tumor confined to uterus. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: (T2, M0, Risk factors: unknown); IIA (T2, M0, Risk factors: low risk); IIB (T2, M0, Risk factors: high risk). T2: Tumor extends to other genital structures (ovary, tube, vagina, broad ligaments) by metastasis or direct extension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIA includes: T2, M0, Risk factors: low risk. T2: Tumor extends to other genital structures (ovary, tube, vagina, broad ligaments) by metastasis or direct extension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: T2, M0, Risk factors: high risk. T2: Tumor extends to other genital structures (ovary, tube, vagina, broad ligaments) by metastasis or direct extension. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: (Any T, M1a, Risk factors: unknown); IIIA (Any T, M1a, Risk factors: low risk); IIIB (Any T, M1a, Risk factors: high risk). M1a: Lung metastasis. (AJCC 7th ed.)
Stage IIIA includes: Any T, M1a, Risk factors: low risk. M1a: Lung metastasis. (AJCC 7th ed.)
Stage IIIB includes: Any T, M1a, Risk factors: high risk. M1a: Lung metastasis. (AJCC 7th ed.)
Stage IV includes: (Any T, M1b, Risk factors: unknown); IVA (Any T, M1b, Risk factors: low risk); IVB (Any T, M1b, Risk factors: high risk). M1b: All other distant metastasis. (AJCC 7th ed.)
Stage IVA includes: Any T, M1b, Risk factors: low risk. M1b: All other distant metastasis. (AJCC 7th ed.)
Stage IVB includes: Any T, M1b, Risk factors: high risk. M1b: All other distant metastasis. (AJCC 7th ed.)
A bisulfate salt form of sulfamethazine, a sulfonamide antibiotic used in the lifestock industry.
A sulfone drug that is converted to dapsone in the body. It has been used to treat mycobacterial infections, including tuberculosis and leprosy.
An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption.
The sulfate salt of vinzolidine, an orally active semisynthetic vinca alkaloid with potential antineoplastic activity. Like other vinca alkaloid compounds, vinzolidine binds to and stabilizes tubulin molecules, thereby interfering with microtubule assembly/disassembly dynamics. As a result, vinzolidine prevents mitotic spindle formation and leads to cell cycle arrest in metaphase.
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Lip and oral cavity cancer with moderately advanced local disease. Lip: Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose. Oral cavity: Tumor invades adjacent structures only (e.g., through cortical bone [mandible or maxilla] into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face). T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension. T3: Tumor more than 4 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: (Any T, N3, M0); (T4b, Any N, M0). T4b: Lip and oral cavity cancer with very advanced local disease. Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
The anhydrous form of a broad-spectrum, semisynthetic aminopenicillin antibiotic with bactericidal activity. Amoxicillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This interrupts bacterial cell wall synthesis and results in the weakening of the bacterial cell wall and causes cell lysis.
An orally administered prodrug with activity against the hepatitis C virus (HCV). Balapiravir is a tri-isobutyrate ester prodrug of R1479, a nucleoside analogue inhibitor of HCV RNA-dependent RNA polymerase.
A hydrochloride salt form of balapiravir, an orally administered prodrug with activity against the hepatitis C virus (HCV). Balapiravir is a tri-isobutyrate ester prodrug of R1479, a nucleoside analogue inhibitor of HCV RNA-dependent RNA polymerase.
A potent, water soluble, selective and orally bioavailable, boronic acid-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Dutogliptin irriversibly binds to DPP-4.
The tartrate salt form of dutogliptin, a potent, water soluble, selective and orally bioavailable, boronic acid-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Dutogliptin irriversibly binds to DPP-4.
A chromosomal translocation that involves chromosome 16. It is often associated with the development of acute myeloid leukemia CBFB-MYH11, acute myelomonocytic leukemia with abnormal eosinophils, and granulocytic sarcoma.
An indication that the subject is currently producing milk.
A finding referring to a medical device that has been placed in the body, usually during a surgical procedure.
Prothrombin (622 aa, ~70 kDa) is encoded by the human F2 gene. This protein plays a role in both coagulation and proteolysis of fibrinogen.
One of two possible results of a pass/fail assessment; when the result satisfies a condition.
Autosomal recessive spastic paraplegia-46 (SPG46) is a neurodegenerative disorder characterized by onset in childhood of slowly progressive spastic paraplegia and cerebellar signs. Some patients have cognitive impairment, cataracts, and cerebral, cerebellar, and corpus callosum atrophy on brain imaging (summary by Boukhris et al., 2010 and Martin et al., 2013).
A sleep disorder characterized by excessive sleepiness and drowsiness.
A small molecule phosphoramidate derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) with potential antineoplastic activity. Selectively active against tumor cells expressing high levels of thymidylate synthase (TS), brivudine is converted intracellularly by TS to bromovinyldeoxyuridine monophosphate (BVdUMP) which competes with the natural substrate, deoxyuridine monophosphate, for binding to TS. Unlike TS inhibitors, this agent is a reversible substrate for TS catalysis. Thus, TS retains activity and converts BVdUMP into cytotoxic metabolites. As key enzyme in the de novo synthesis of dTMP, TS is an enzyme critical to DNA biosynthesis and is overexpressed in many solid tumors.
Gastritis caused by injury to the gastric mucosa by chemicals. The injury occurs due to reflux of bile and pancreatic enzymes.
A genetically-modified autologous dendritic cell-based vaccine expressing a drug-inducible costimulatory CD40 receptor (iCD40) with potential immunomodulating and antineoplastic activities. Autologous dendritic cells (DCs) are genetically modified to express the iCD40 receptor and are pulsed with the tumor antigen prostate-specific membrane antigen (PSMA). Upon intradermal administration, these DCs accumulate in local draining lymph nodes. Twenty-four hours after vaccination, the dimerizer agent AP1903 is administered; AP1903 binds to and activates iCD40 receptors presented on DC surfaces, thus activating the DCs and stimulating a cytotoxic T-lymphocyte (CTL) response against host tumor cells that express PSMA. This delayed activation strategy optimizes DC accumulation in local draining lymph nodes prior to DC activation. iCD40 contains a membrane-localized cytoplasmic CD40 domain fused to a drug-binding domain.
An orally bioavailable inhibitor of vascular endothelial growth factor receptor (VEGFR) and Tie2 receptor tyrosine kinases with potential antiangiogenic and antineoplastic activities. Pan-VEGFR/Tie2 tyrosine kinase inhibitor CEP-11981 selectively binds to VEGFR and Tie2 receptor tyrosine kinases, which may result in the inhibition of endothelial cell migration, proliferation and survival and the inhibition of tumor cell proliferation and tumor cell death. VEGFR and Tie2 are frequently overexpressed by a variety of tumor cell types and play crucial roles in the regulation of angiogenesis and the maintenance of tumor blood vessels. Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains) is activated by angiopoietin-1 (Ang-1).
An orally bioavailable inhibitor of human heat-shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor Hsp990 binds to and inhibits the activity of Hsp90, which may result in the proteasomal degradation of oncogenic client proteins, including HER2/ERBB2, and the inhibition of tumor cell proliferation. Hsp90, upregulated in a variety of tumor cells, is a molecular chaperone that plays a key role in the conformational maturation, stability and function of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation and/or immune responses.
An orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Afuresertib binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
A retinobenzoic acid with potential antineoplastic activity. Amsilarotene inhibits retinoblastoma-gene product (RB) phosphorylation and increases the presence of 2 cyclin-dependent kinase (CDK) inhibitors, resulting in cell cycle arrest. This agent also causes a cytotoxic decline in cyclin A and thymidylate synthase expression.
An orally active inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRb), and the ephrin B4 receptor B4 (EphB4) with potential antiangiogenic and antineoplastic activities. Angiogenesis inhibitor JI-101 binds to and inhibits VEGFR2, PDGFRb and EphB4, which may inhibit tumor angiogenesis and, so, cellular proliferation in tumor cells overexpressing VEGFR2, PDGFRb and EphB4. The receptor tyrosine kinases VEGFR2, PDGFRb and EphB4 may be overexpressed in a number of different cancer cell types and may play crucial roles in tumor angiogenesis.
The dihydrochloride salt of efatutazone, an orally bioavailable agonist of peroxisome proliferator-activated receptor gamma (PPAR-gamma) with potential antineoplastic activity. Efatutazone binds to and activates PPAR-gamma, a nuclear hormone receptor and a ligand-activated transcription factor controling gene expression involved in macromolecule metabolism and cell differentiation, specifically adipocyte differentiation. Mediated through activation of PPAR-gamma, this agent is capable of inducing cell differentiation and apoptosis, thereby leading to a reduction in cellular proliferation.
A semi-synthetic derivative of the natural taxoid 10-deacetylbaccatin III with potential antineoplastic activity. Cabazitaxel binds to and stabilizes tubulin, resulting in the inhibition of microtubule depolymerization and cell division, cell cycle arrest in the G2/M phase, and the inhibition of tumor cell proliferation. Unlike other taxane compounds, this agent is a poor substrate for the membrane-associated, multidrug resistance (MDR), P-glycoprotein (P-gp) efflux pump and may be useful for treating multidrug-resistant tumors. In addition, cabazitaxel penetrates the blood-brain barrier (BBB).
An orally active small molecule, targeting mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), with potential antineoplastic activity. MEK inhibitor RO4987655 binds to and inhibits MEK, which may result in the inhibition of MEK-dependent cell signaling and the inhibition of tumor cell proliferation. MEK, a dual specificity threonine/tyrosine kinase, is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.
A form of dyskinetic cerebral palsy with involuntary movements accompanied by an abnormal, sustained posture.
A restrictive cardiopathy with manifestation of endocardial fibrosis. This disorder occurs almost exclusively in tropical and subtropical regions. The prevalence is unknown but the disorder is extremely rare in Europe. The fibrosis may affect the right ventricle (leading to adiastole with tricuspid insufficiency) or the left ventricle (causing acute mitral insufficiency, and early and severe pulmonary hypertension). The fibrosis can also be bilateral. The cause is unknown.
Hypertension that develops following long-standing compression of renal parenchyma by sub-capsular renal collection, e.g. haematoma, seroma, urinoma.
A condition which occurs in monozygotic twins in which one of the fetuses supplies the majority of the cardiac output to its co-twin through its umbilical artery. The recipient twin has only rudimentary organs and structure and is not viable.
A ureterocele in which the orifice is located in the bladder, with the ureterocele pouch extending submucosally into the urethra.
A finding characterized by a decrease in overall body weight; for pediatrics, less than the baseline growth curve.
A disorder characterized by bleeding from the vagina.
A finding characterized by an unexpected or abnormal increase in overall body weight; for pediatrics, greater than the baseline growth curve.
An electrocardiographic finding suggestive of an enlarged cardiac ventricle.
An indication or description that a particular disorder is being managed successfully.
Any substance that inhibits dihydrofolate reductase, an enzyme that catalyzes the conversion of dihydrofolate to tetrahydrofolate, an essential reaction for de novo glycine and purine synthesis. Inhibition of dihydrofolate reductase interferes with DNA and protein synthesis.
Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.
A highly charged polymeric agent use to bind bile acids in the gastrointestinal tract and prevent their reabsorption from the gut. The bound bile acids are excreted with the feces and plasma cholesterol is converted to bile acid to reestablish normal bile acid levels, resulting in a lowering of plasma cholesterol concentrations.
An adverse event that is medically significant but not life-threatening; or for which inpatient care or prolongation of hospitalization are indicated; or that is an important medical event that does not result in hospitalization, but may jeopardize the patient or may require intervention either to prevent hospitalization, to prevent the AE from becoming life-threatening or causing death; or that is disabling; or that results in persistent or significant disability, incapacity, or limitation of self care activities of daily living (ADLs, e.g., getting in and out of bed, dressing, eating, getting around inside, bathing, or using the toilet).
Myocardial tissue which exhibits characteristics of inadequate blood flow.
An abnormal accumulation of fluid beneath the skin on the back of the feet.
The loss of continuity between the left subclavian artery and the aorta, with persistent connection to the homolateral pulmonary artery through the patent (PDA) or nonpatent ductus arteriosus. [MP:0011745]
Undertaking a trip from one place to another via aircraft in the sufficiently recent past to be relevant to some current health issue
IgA nephropathy secondary to a genetic mutation that is transmitted from parents to offspring.
A designation that a patient has chosen not to heed the directions that medical staff has advised, and has chosen to leave the facility.
An acute myeloid leukemia associated with t(9;11)(p22.3;q23.3) and MLLT3-KMT2A fusion protein expression. Morphologically it usually has monocytic features. It may present at any age but it is more commonly seen in children. Patients may present with disseminated intravascular coagulation.
Right-axis deviation with frontal QRS axis between 90° and 180° rS in leads I and aVL and qR in inferior leads (Q waves 40 ms); QRS duration 120 ms; Exclude other causes of right-axis deviation.
Type II diabetes mellitus in which there are frequent, clinically significant fluctuations in blood glucose levels both above and below levels expected to be achieved by available therapies.
An anatomical variant of the cervical vertebra axis in which the ODONTOID PROCESS is unfused from the body of the axis.
Urolithiasis in which the composition of the stone(s) is predominantly magnesium ammonium phosphate.
Pregnancy loss before 5th week of gestation with no gestational sac visible on ultrasonogram.
A gap (cleft) affecting one of the alveolar ridges, which are the protuberances in the mouth that contain the sockets (alveoli) of the teeth. An alveolar cleft can affect all structures of the alveolar ridge, including the gingiva, other mucosa, periosteum, alveolar bone, and teeth. [HPO:mengelstad, HPO:probinson]
Disturbances in the normal fluency and time patterning of speech that are inappropriate for the individual's age and language skills. (DSM-V)
A first neurologic episode caused by inflammation/demyelination of one or more central nervous system sites that lasts at least 24 hours.
Inability of primary caregiver to create, maintain or regain an environment that promotes the optimum growth and development of the child.
A calculated result that uses the following formula to quantify both systolic and diastolic ventricular function: MPI = IVCT + IVRT) / V ET, in which IVCT is isovolumetric contraction time, IVRT is isovolumetric relaxation time, and V ET is ventricular ejection time.
The leakage of a substance from an orifice or wound.
Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.
Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.
Inhibitor or Reverse Transcriptases or of RNA-dIrected DNA polymerase.
An oral suspension containing aluminum hydroxide and magnesium hydroxide, with antacid effects. Aluminum hydroxide and magnesium hydroxide neutralizes or reduces gastric acid, thereby relieving symptoms associated with indigestion, gastritis, and gastroesophageal disease (GERD). Combined with other liquid ingredients (such as lidocaine and diphenhydramine), this antacid provides relief for painful stomatitis, mucositis, and esophagitis associated with both chemotherapy and radiation therapy.
A fused tricyclic analogue of flavone acetic acid with potential antineoplastic activity. Vadimezan induces the cytokines tumor necrosis alpha (TNF-alpha), serotonin and nitric oxide, resulting in hemorrhagic necrosis and a decrease in angiogenesis. This agent also stimulates the anti-tumor activity of tumor-associated macrophages.
The hydrochloride salt of a modified glutathione analogue with potential antineoplastic activity. Canfosfamide is selectively activated by glutathione S-transferase P1-1 into an alkylating metabolite that forms covalent linkages with nucleophilic centers in tumor cell DNA, which may induce a cellular stress response and cytotoxicity, and decrease tumor proliferation. S-transferase P1-1 is an enzyme that is overexpressed in many human malignancies.
A congenital disorder characterized by abnormalities in the development of the sexual characteristics.
Chemically-engineered hemoglobin-based oxygen carriers or ARTIFICIAL HEMOGLOBIN oxygen carriers. They may or may not be encapsulated by ARTIFICIAL MEMBRANES.
An orally available inhibitor of Janus kinases (JAK), with immunomodulatory and anti-inflammatory activities. Upon administration, tofacitinib binds to JAK and prevents the activation of the JAK-signal transducers and activators of transcription (STAT) signaling pathway. This may decrease the production of pro-inflammatory cytokines, such as interleukin (IL)-6, -7, -15, -21, interferon-alpha and -beta, and may prevent both an inflammatory response and the inflammation-induced damage caused by certain immunological diseases. JAK kinases are intracellular enzymes involved in signaling pathways affecting hematopoiesis, immunity and inflammation.
Gel dressing used for debridement (cleaning) of deep burns in hospitalized patients.
Used in World War I to designate a wide variety of MENTAL DISORDERS presumably due to combat experience. from Americanl Psychiatric Glossary, 7th ed.
Reactions to fierce combat or operations other than war, which may be both physical and psychological.
An orally bioavailable, indolinone-derived, receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities. Multitargeted tyrosine kinase inhibitor BIBF 1120 selectively binds to and inhibits vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and platelet-derived growth factor receptor (PDGFR) tyrosine kinases, which may result in the induction of endothelial cell apoptosis; a reduction in tumor vasculature; and the inhibition of tumor cell proliferation and migration. In addition, this agent also inhibits members of the Src family of tyrosine kinases, including Src, Lck, Lyn, and FLT-3 (fms-like tyrosine kinase 3). VEGFR, FGFR and PDGFR RTKs play key roles in tumor angiogenesis.
, mainly occurring in tropical regions after the ingestion of an amoebic cyst, and resulting in clinical manifestations that may range from an asymptomatic state to amoebic colitis (violent abdominal pain, a painful contracted feeling around the anal sphincter, blood and mucus in the stools but without the presence of fever), or amoebic liver abscesses (fever, chills, abdominal pain, weight loss, hepatomegaly) that can be fatal if not immediately treated. Extraintestinal involvement elsewhere (i.e. thoracic, hepatic) is extremely rare.
The designation 'antiphospholipid syndrome' was proposed for the association of arterial and venous thrombosis, recurrent fetal loss, and immune thrombocytopenia with a spectrum of autoantibodies directed against cellular phospholipid components. Anticardiolipin antibodies may react with cardiolipin and with other negatively charged phospholipids, including beta-2-glycoprotein I (B2GPI, APOH; 138700). The term 'lupus anticoagulant' refers to a heterogeneous group of antibodies, most commonly of the IgG type, that are detected by their inhibitory effect on coagulant-active phospholipid components of in vitro coagulation tests (summary by Matthey et al., 1989). Shoenfeld et al. (2008) noted that antiphospholipid syndrome is characterized by up to 30 different autoantibodies, including those against platelets, glycoproteins, coagulation factors, lamins, mitochondrial antigens, and cell surface markers. Some of these may have an additive effect on the prothrombotic tendency of the syndrome. Ruiz-Irastorza et al. (2010) reviewed pathophysiologic, clinical, diagnostic, and therapeutic advances related to the antiphospholipid syndrome. Various autoimmune disorders that cluster in families, including autoimmune thrombocytopenia (188030), are discussed elsewhere (e.g., 109100, 269200).
Swelling of the optic disc in the absence of increased intracranial pressure.
Retinal ischemic syndrome-digestive tract small vessel hyalinosis-diffuse cerebral calcifications syndrome is characterized by progressive hyalinosis involving capillaries and often arterioles and small veins of the digestive tract, kidneys, and idiopathic cerebral calcifications. It has been described in three sisters born to non-consanguineous parents. All three patients also had poikilodermia and greying hair, as well as severe diarrhoea, rectal bleeding, malabsorption and subarachnoid hemorrhage.
An abnormal osseous union (fusion) between the radius and the humerus.
An extremely rare genetic disorder characterised by corneal anaesthesia, retinal abnormalities, bilateral hearing loss, distinct facies, patent ductus arteriosus, Hirschsprung disease, short stature and intellectual disability. The phenotype is variable. Some affected individuals have only mild disease manifestations. The aetiology of this syndrome is not yet known. Mutations in an as of yet unidentified gene, involved in autonomic nervous system function, are suspected. Follows an autosomal dominant pattern of inheritance, probably with variable expressivity.
A rare, progressive chronic inflammation of a single cerebral hemisphere that usually affects children. It is characterized by severe seizures, loss of motor skills and speech, hemiparesis, and dementia.
This syndrome manifests with mesomelic shortening and bowing of the limbs, camptodactyly, skin dimpling and cleft palate with retrognathia and mandibular hypoplasia. Transmission is autosomal recessive.
A rare chromosomal anomaly syndrome with a highly variable phenotype. Principle characteristics are intellectual disability, growth and developmental delay, facial dysmorphism (including microphthalmia, deep-set eyes, low-set, malformed ears, bulbous nose, high-arched palate, micrognathia) and congenital heart defects (ventricular septal defect), as well as urogenital (hypoplastic genitalia, cryptorchidism), skeletal (congenital joint dislocations or hyperflexion, scoliosis/kyphosis) and central nervous system anomalies (hydrocephalus, Dandy-Walker malformation). Pigmentary mosaic skin lesions along the lines of Blaschko are also frequently observed.
A cytogenetic abnormality that refers to the allelic loss of all or part of the long arm of chromosome 13.
Ring chromosome 14 syndrome is a condition characterized by seizures and intellectual disability. Recurrent seizures (epilepsy) develop in infancy or early childhood. In many cases, the seizures are resistant to treatment with anti-epileptic drugs. Most people with ring chromosome 14 syndrome also have some degree of intellectual disability or learning problems. Development may be delayed, particularly the development of speech and of motor skills such as sitting, standing, and walking.Additional features of ring chromosome 14 syndrome can include slow growth and short stature, a small head (microcephaly), puffy hands and/or feet caused by a buildup of fluid (lymphedema), and subtle differences in facial features. Some affected individuals have problems with their immune system that lead to recurrent infections, especially involving the respiratory system. Abnormalities of the retina, the specialized tissue at the back of the eye that detects light and color, have also been reported in some people with this condition. These changes typically do not affect vision. Major birth defects are rarely seen with ring chromosome 14 syndrome.
A rare chromosomal anomaly disorder with a highly variable phenotype. Principle characteristics are growth and developmental delay, intellectual disability, body asymmetry/hypotonia, congenital heart defects, genitourinary abnormalities (cryptorchidism, micropenis, large clitoris, labial swelling), and abnormal skin hyperpigmentation. Patients usually present with craniofacial dysmorphism such as microcephaly, abnormal palpebral fissure, hypertelorism, ear abnormalities, broad nose, low-set ears, micro/retrognathia and cleft or highly arched palate.
This syndrome has characteristics of short stature, intellectual deficit, facial dysmorphism, short webbed neck, skin changes and congenital heart defects. It has been reported in four Arab Bedouin siblings born to consanguineous parents.
A form of ectodermal dysplasia syndrome with characteristics of trichodysplasia, with absent eyebrows and eyelashes, onychodysplasia, mild retrognathia, abnormal dermatoglyphics (excess of whorls on fingertips, radial loop on finger, hypothenar pattern), intellectual disability and normal teeth and sweating. Additional variable manifestations include high implanted or prominent ears, mild hearing loss, supernumerary nipple, café-au-lait spots, keratosis pilaris, and irregular menses. To date, four individuals from 2 generations of a consanguineous family of Portuguese descent have been described in the literature. Males and females were equally affected. Hidrotic ectodermal dysplasia, Halal type is inherited in an autosomal recessive manner.
This syndrome is characterised by the combination of microcephaly, cleft palate, and variable anomalies such as unusual facial appearance, hypotelorism, abnormal retinal pigmentation, maxillary hypoplasia, goitre, camptodactyly, mild intellectual deficit, and abnormal dermatoglyphics. It has been described only once; in two sisters and their mother. Although microcephaly and intellectual deficit are frequently associated with cleft palate, the other features of these patients are in favour of this syndrome being an entity per se. The mode of inheritance is autosomal or X-linked dominant.
A well-differentiated neuroendocrine tumor arising from the digestive system. It is characterized by the presence of cells with features similar to those of the normal endocrine cells of the digestive system. The neoplastic cells express immunohistochemical evidence of neuroendocrine differentiation and hormones. There is mild to moderate nuclear atypia and less than 20 mitoses per 10 HPF. It includes well-differentiated endocrine tumors or carcinoid tumors and well-differentiated endocrine carcinomas.
The Hunter-Thompson type of acromesomelic dysplasia is characterized by skeletal abnormalities restricted to the limbs; the craniofacial skeleton and axial skeletal structures are normal. The severity of the long bone shortening progresses in a proximal to distal direction. The hands and feet are most severely affected, but the distal phalanges are relative normal. Affected individuals have joint dislocations but the number of joints involved is not constant (summary by Thomas et al., 1996).
Congenital disorders of glycosylation, previously called carbohydrate-deficient glycoprotein syndromes (CDGSs), are caused by defects in mannose addition during N-linked oligosaccharide assembly. CDGs can be divided into 2 types, depending on whether they impair lipid-linked oligosaccharide (LLO) assembly and transfer (CDG I), or affect trimming of the protein-bound oligosaccharide or the addition of sugars to it (CDG II) (Orlean, 2000). CDG Ic is characterized by psychomotor retardation with delayed walking and speech, hypotonia, seizures, and sometimes protein-losing enteropathy. It is the second largest subtype of CDG (summary by Sun et al., 2005). For a discussion of the classification of CDGs, see CDG1A (212065). Freeze and Aebi (1999) reviewed CDG Ib (602579) and CDG Ic.
Congenital disorders of glycosylation (CDG), previously called carbohydrate-deficient glycoprotein syndromes (CDGSs), are a group of hereditary multisystem disorders first recognized by Jaeken et al. (1980). The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing (IEF) of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans. For a general discussion of CDGs, see CDG1A (212065) and CDG1B (602579).
CDGs, previously called carbohydrate-deficient glycoprotein syndromes, grew from hereditary multisystem disorders first recognized by Jaeken et al. (1980). The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans. For a general discussion of CDGs, see CDG1A (212065). CDG1H is a severe form of CDG. The majority of patients have brain involvement, liver pathology, gastrointestinal symptoms, dysmorphism (including brachydactyly), eye involvement (especially cataract), and skin symptoms. Most patients die within the first year of life (summary by Marques-da-Silva et al., 2017).
Like all CDGs, which are caused by a shortage of precursor monosaccharide phosphate or deficiencies in the glycosyltransferases required for lipid-linked oligosaccharide precursor (LLO) synthesis, CDG Ij is caused by a defect in the formation of DPAGT1, the first dolichyl-linked intermediate of the protein N-glycosylation pathway. For a general discussion of CDGs, see CDG1A (212065).
Congenital disorders of glycosylation (CDGs) comprise a group of multisystem diseases with mostly severe psychomotor and mental retardation. Type I CDG comprises those disorders in which there are defects that affect biosynthesis of dolichol-linked oligosaccharides in the cytosol or the endoplasmic reticulum (ER), as well as defects involving the transfer of oligosaccharides onto nascent glycoproteins. Type II CDG comprises all defects of further trimming and elongation of N-linked oligosaccharides in the ER and Golgi (Schwarz et al., 2004). CDG1K is a type I CDG characterized by predominant neurologic involvement. Survival ranges from the second day of life to adulthood. The liver is affected in a minority of patients and shows hepatomegaly, edema, ascites, cholestatic jaundice, portal hypertension, and Budd-Chiari syndrome (summary by Marques-da-Silva et al., 2017). For a general discussion of CDGs, see CDG1A (212065).
Congenital disorders of glycosylation (CDGs) that represent defects of dolichol-linked oligosaccharide assembly are classified as CDG type I. For a general description and a discussion of the classification of CDGs, see CDG1A (212065).
A form of congenital disorders of N-linked glycosylation with characteristics of intrauterine growth retardation, microcephaly, failure to thrive, developmental delay, intellectual disability, hypotonia, seizures, optic nerve atrophy and respiratory difficulties. Genital abnormalities (micropenis, hypoplastic scrotum, undescended testes) have also been reported. Caused by mutations in the gene STT3B (3p24.1).
Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of autosomal recessive disorders caused by enzymatic defects in the synthesis and processing of asparagine (N)-linked glycans or oligosaccharides on glycoproteins. These glycoconjugates play critical roles in metabolism, cell recognition and adhesion, cell migration, protease resistance, host defense, and antigenicity, among others. CDGs are divided into 2 main groups: type I CDGs (see, e.g., CDG1A, 212065) comprise defects in the assembly of the dolichol lipid-linked oligosaccharide (LLO) chain and its transfer to the nascent protein, whereas type II CDGs refer to defects in the trimming and processing of the protein-bound glycans either late in the endoplasmic reticulum or the Golgi compartments. The biochemical changes of CDGs are most readily observed in serum transferrin (TF; 190000), and the diagnosis is usually made by isoelectric focusing of this glycoprotein (reviews by Marquardt and Denecke, 2003; Grunewald et al., 2002). Genetic Heterogeneity of Congenital Disorder of Glycosylation Type II Multiple forms of CDG type II have been identified; see CDG2B (606056) through CDG2Q (617395).
Congenital disorders of glycosylation (CDG) are a group of hereditary multisystem disorders that are commonly associated with severe psychomotor and mental retardation. The characteristic biochemical abnormality of CDGs is the hypoglycosylation of glycoproteins, which is routinely determined by isoelectric focusing (IEF) of serum transferrin. Type I CDG comprises those disorders in which there is a defect in the assembly of lipid-linked oligosaccharides or their transfer onto nascent glycoproteins, whereas type II CDG comprises defects of trimming, elongation, and processing of protein-bound glycans (summary by Hansske et al., 2002). For a general discussion of CDGs, see CDG1A (212065).
CDG IIe is caused by a mutation that impairs the integrity of the conserved oligomeric Golgi (COG) complex and alters Golgi trafficking, resulting in the disruption of multiple glycosylation pathways. For a general discussion of CDGs, see CDG1A (212065).
An extremely rare form of carbohydrate deficient glycoprotein syndrome with, in the few cases reported to date, variable signs including microcephaly, growth retardation, psychomotor retardation and facial dysmorphism.
Split-hand/foot malformation (SHFM) is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM1 have been found to have mental retardation, ectodermal and craniofacial findings, orofacial clefting (Elliott and Evans, 2006), and neurosensory hearing loss (Tackels-Horne et al., 2001). Genetic Heterogeneity of Split-Hand/Foot Malformation Additional SHFM loci include SHFM2 (313350) on chromosome Xq26; SHFM3 (246560), caused by duplication of chromosome 10q24; SHFM4 (605289), caused by mutation in the TP63 gene (603273) on chromosome 3q27; SHFM5 (606708) on chromosome 2q31; and SHFM6 (225300), caused by mutation in the WNT10B gene (601906) on chromosome 12q13. Also see SHFM1D (220600) for a form of SHFM1 with deafness that may be caused by homozygous mutation in the DLX5 gene (600028).
This syndrome is characterized by the association of Möbius syndrome (congenital facial palsy with impaired ocular abduction; see this term) with peripheral axonal neuropathy and hypogonadotropic hypogonadism.
A very rare ectodermal dysplasia syndrome with the association of choroidal atrophy (sometimes regional), together with other ectodermal dysplasia features including fine and sparse hair, absent or decreased lashes and eyebrows, and possibly mild visual loss and dysplastic/thick/grooved nails.
A rare genetic capillary malformation characterised by dark red to purple birthmarks which manifest as flat, sharply circumscribed cutaneous lesions, typically situated in the head and neck region, in various members of a single family. The lesions grow proportionally with the individual, change in colour and often thicken with age. There is evidence that congenital capillary malformations can be caused by somatic mosaic mutation in the GNAQ gene on chromosome 9q21.
A benign proliferation of the stromal cells in the breast. It is classified as simple, when associated with the presence of slit-like spaces without erythrocytes and as fascicular/proliferative, when spindle cell proliferation without atypia is present. It is often seen in breast tissue specimens as small foci associated with benign epithelial lesions. Pseudoangiomatous stromal hyperplasia presenting as a well-circumscribed palpable mass is rare.
A carcinoma that arises from the pancreas in a patient with a family history of pancreatic cancer. In the minority of cases, patients have recognized genetic syndromes (e.g., FAMMM syndrome, BRCA2 syndrome, Peutz-Jeghers syndrome) however, in the majority of cases the genetic cause has not been identified.
Hawkinsinuria is an autosomal dominant inborn error of metabolism (Danks et al., 1975; Tomoeda et al., 2000). Metabolic acidosis and tyrosinemia are transient, and symptoms improve within the first year of life. Patients continue to excrete the hawkinsin metabolite in their urine throughout life.
Greenberg dysplasia, also known as hydrops-ectopic calcification-moth-eaten (HEM) skeletal dysplasia, is a rare autosomal recessive osteochondrodysplasia characterized by gross fetal hydrops, severe shortening of all long bones with a moth-eaten radiographic appearance, platyspondyly, disorganization of chondroosseous calcification, and ectopic ossification centers. It is lethal in utero. Patient fibroblasts show increased levels of cholesta-8,14-dien-3-beta-ol, suggesting a defect of sterol metabolism (summary by Konstantinidou et al., 2008). Herman (2003) reviewed the cholesterol biosynthetic pathway and 6 disorders involving enzyme defects in postsqualene cholesterol biosynthesis: Smith-Lemli-Opitz syndrome (SLOS; 270400), desmosterolosis (602398), X-linked dominant chondrodysplasia punctata (CDPX2; 302960), CHILD syndrome (308050), lathosterolosis (607330), and HEM skeletal dysplasia.
The association of camptodactyly, multiple eye defects (fibrosis of the medial rectus muscle, severe myopia, ptosis and exophthalmos), scoliosis, flexion contractures and facial anomalies (arched eyebrows, facial asymmetry with an abnormal skull shape, a prominent nose, small mouth, low-set and dysplastic ears, and a low nuchal hairline). Only four cases have been reported in the literature so far. The mode of inheritance remains to be confirmed, but both autosomal dominant and recessive transmission have been considered.
A clinical entity that can present as variable anomalies of the caudal pole. It has been described in four siblings and their father's half-sister. The first sibling had aberrant umbilical cord vasculature with a single umbilical artery near the placental insertion. Two of the siblings showed full sirenomelia, one with a complex congenital heart defect. The fourth case had an imperforate anus and an excessively long umbilical cord. The half-sister had an imperforate anus, rectovaginal fistula and genitourinary anomalies. The syndrome appears to be expressed as a dominant trait with reduced penetrance and variable expressivity.
Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant hair loss disorder characterized by the absence or scarcity of scalp hair, eyebrows, and eyelashes at birth; coarse and wiry hair during childhood; and progressive hair loss beginning around puberty.
Syndrome with characteristics of skeletal dysplasia associated with finger malformations (brachydactyly with short and abducted thumbs, short index fingers, and markedly short and abducted great toes), variable mild short stature and mild bowleg with overgrowth of the fibula. It has been described in two males, their mothers, and a maternal aunt. Females are less severely affected than males. X-linked dominant inheritance is suggested.
The association of Pierre Robin sequence (retrognathia, cleft palate and glossoptosis), facial dysmorphism (high forehead with frontal bossing) and digital anomalies (tapering fingers, hyper convex nails, clinodactyly of the fifth fingers and short distal phalanges, finger-like thumbs and easily subluxated first metacarpophalangeal joints). Growth and mental development are normal. It has been described in two half brothers born to the same mother. Transmission appears to be X-linked recessive.
A very rare bone disease reported in two siblings with characteristics of bowed tibia, hypoplastic thumbs, multiple fractures, distinctive facial features and developmental delay. There have been no further descriptions in the literature since 1993.
This syndrome has characteristics of nephrogenic diabetes insipidus, intracerebral calcifications, intellectual deficit, short stature and facial dysmorphism. It has been described in two siblings.
A very rare disorder with characteristics of autoimmunity, lymphadenopathy and/or splenomegaly. The prevalence is not known. The disorder has been reported in fewer than 30 patients to date. Age of onset is highly variable, ranging from childhood to young adulthood. A possible increased risk of cancer has been suggested in these patients. The cause is not known but it is thought to be hereditary. Biologically, DALD has characteristics of normal double-negative T-cells (DNTs) and defective in vitro FAS-mediated apoptosis. The pattern of inheritance of DALD is not known.
Epidermolysis bullosa simplex with muscular dystrophy is an autosomal recessive disorder characterized by early childhood onset of progressive muscular dystrophy and blistering skin changes (Fine et al., 1989). Fine et al. (1991) reported a revised classification of the subtypes of inherited epidermolysis bullosa. In reports of 2 consensus meetings on EB, Fine et al. (2000, 2008) referred to EB with muscular dystrophy due to PLEC1 mutations as a form of basal simplex EB. Fine et al. (2000, 2008) also eliminated the term 'hemidesmosomal,' which had previously been proposed for this entity (Uitto et al., 1997) because ultrastructural analysis can demonstrate tissue abnormalities of the hemidesmosomes.
A rare subtype of Leigh syndrome with clinical characteristics of encephalopathy, lactic acidosis, seizures, cardiomyopathy, respiratory disorders and developmental delay. Onset in infancy or early childhood resulting from maternally-inherited mutations in mitochondrial DNA.
Osteogenesis imperfecta is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most forms of OI are autosomal dominant with mutations in one of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Glorieux et al. (2000) described a novel autosomal dominant form of OI, which they designated OI type V, in 7 patients. The disorder was similar to OI type IV but had distinctive clinical, histologic, and molecular characteristics. OI type V is characterized by calcification of the forearm interosseous membrane, radial head dislocation, a subphyseal metaphyseal radiodense line, and hyperplastic callus formation (summary by Cho et al., 2012).
Osteopathia striata-pigmentary dermopathy-white forelock syndrome is characterised by the association of osteopathia striata (longitudinal striations through most of the long bones) with a macular, hyperpigmented dermopathy and a white forelock.
A severe fetal malformation syndrome with characteristics of craniofacial dysmorphic features, central nervous system, cardiac, respiratory tract and limb abnormalities. Mostly present in families of Finnish descent. The syndrome also has characteristics of postaxial and preaxial polydactyly. Caused by mutations in HYLS1 (11q24.2) and KIF7 (15q26.1). Inheritance is autosomal recessive. Stillbirth or neonatal death is the rule, although rare cases with several months' survival have been reported.
Myostatin-related muscle hypertrophy is a rare condition characterized by reduced body fat and increased muscle size. Affected individuals have up to twice the usual amount of muscle mass in their bodies. They also tend to have increased muscle strength. Myostatin-related muscle hypertrophy is not known to cause any medical problems, and affected individuals are intellectually normal.
Ectopia lentis-chorioretinal dystrophy-myopia syndrome is characterised by anomalies of the lens (ectopia and cataracts) and retina (generalized tapetoretinal dystrophy and total retinal detachment). Myopia has also been reported. It has been described in four members of the same family, all resulting from a consanguineous marriage. The mode of transmission is autosomal recessive.
Fetal megacystis is an abnormally enlarged bladder identified at any gestational age.
This syndrome is extremely rare and has characteristics of delayed speech development, mild facial asymmetry, strabismus and transverse ear lobe creases. To date, six cases have been reported in five families. Dysmorphic features include asymmetrical face, unilateral narrow palpebral fissure, divergent strabismus, long philtrum, high-arched palate, apparently low-set ears and transverse ear lobe creases on both sides. Delayed language development is constant but intellectual development can be normal. In one family, the transmission was compatible with either autosomal dominant or X-linked dominant inheritance.
Striate palmoplantar keratoderma belongs to a group of skin diseases in which there is thickening of the skin on the palms and soles. The striate form is characterized by longitudinal hyperkeratotic lesions extending the length of each finger to the palm, and hyperkeratotic lesions are restricted to regions of the body where pressure and abrasion are greatest (summary by Hunt et al., 2001). Patients with diffuse or focal forms of keratoderma associated with mutation in the DSG1 gene have also been reported (Keren et al., 2005; Milingou et al., 2006). Genetic Heterogeneity of Keratosis Palmoplantaris Striata Type II PPKS (PPKS2; 612908) is caused by mutation in the DSP gene (125647) on chromosome 6. Type III PPKS (PPKS3; 607654) is caused by mutation in the keratin-1 gene (KRT1; 139350) on chromosome 12q. For a general phenotypic description and a discussion of genetic heterogeneity of palmoplantar keratoderma (PPK), see epidermolytic PPK (144200). Nitoiu et al. (2014) reviewed desmosome biology in cardiocutaneous syndromes and inherited skin disease, including discussion of the involvement of the DSG1 and DSP genes.
This syndrome has characteristics of sensorineural deafness, diabetes mellitus, progressive neurological deterioration with photomyoclonic epilepsy, and progressive nephropathy. It has been described in two brothers. Premature atherosclerosis of renal, coronary, and cerebral arteries and the aorta was also observed.
A very rare syndrome with the combination of microcephaly, heart defects, renal hypoplasia, lung segmentation defects and cleft palate. It has been described in three female siblings. Dysmorphic features were not characteristic. The condition seems to be hereditary, and transmitted as an autosomal recessive trait. Prognosis is poor and all children died in infancy.
The hereditary hyperbilirubinemias (Wolkoff et al., 1983) include (1) those resulting in predominantly unconjugated hyperbilirubinemia: Gilbert or Arias syndrome, Crigler-Najjar syndrome type I, and Crigler-Najjar syndrome type II; and (2) those resulting in predominantly conjugated hyperbilirubinemia: Dubin-Johnson syndrome (237500), Rotor syndrome (237450), and several forms of intrahepatic cholestasis (147480, 211600, 214950, 243300). Detailed studies show that patients with Crigler-Najjar syndrome type II have reduced activity of bilirubin glucuronosyltransferase (Labrune et al., 1989, Seppen et al., 1994).
Morquio syndrome is an autosomal recessive mucopolysaccharidosis characterized by short trunk dwarfism, fine corneal opacities, skeletal changes, and normal intelligence. Morquio syndromes A (MPS4A; 253000) and B (MPS4B; 253010) are caused by mutations in the N-acetylglucosamine-6-sulfate sulfatase (GALNS; 612222) and beta-galactosidase (GLB1; 611458) genes, respectively. MPS4A and MPS4B are characterized biochemically by increased urinary excretion of keratan sulfate (Beck et al., 1986). There is some evidence of an additional form of Morquio syndrome, referred to here as type C, in which urinary excretion of keratan sulfate is absent. However, McKusick (1972) suggested that the nonkeratosulfate- excreting Morquio syndrome may be allelic to other forms of Morquio syndrome.
This syndrome is characterised principally by non-progressive central hypotonia, chronic constipation, severe psychomotor retardation, abnormal dermatoglyphics, dysharmonic skeletal maturation and disproportionate muscle fibres. Seizures or an abnormal electroencephalograph were also reported. To date, the syndrome has been reported in three unrelated Puerto Rican boys.
A rare developmental defect during embryogenesis with characteristics of variable upper limb reduction defects and renal anomalies. Patients typically present absence/hypoplasia of digits, radii and/or ulnae, short stature and mild external ear malformation, as well as kidney agenesis or ectopia. There have been no further descriptions in the literature since 1983.
Premature fusion of one of the coronal sutures.
Immunoglobulin (Ig) A deficiency (IGAD) is characterized by decreased or absent levels of serum IgA in the presence of normal serum levels of IgG and IgM in a patient older than 4 years of age in whom other causes of hypogammaglobulinemia have been excluded. IgA in the dimeric form is the dominant immunoglobulin in luminal secretions, such as saliva, tears, bronchial secretions, nasal mucosal secretions, and mucous secretions of the small intestine. Individuals with selective IgA deficiency may be asymptomatic or have recurrent sinopulmonary and gastrointestinal infections, allergic disorders, and autoimmune disorders. The diagnosis of IgA deficiency depends on the measurement of monomeric IgA concentrations in serum; thus individuals with IgA deficiency may have IgA in mucosal systems, which may offer some protection (review by Yel, 2010). Genetic Heterogeneity of IgA Deficiency The IGAD1 locus maps to chromosome 6p21. See also IGAD2 (609529), which is caused by mutation in the TNFRSF13B gene (604907) on chromosome 17p11.
Foetal parvovirus syndrome is a foetopathy likely to occur when a pregnant woman is infected by parvovirus B19. In adults, the virus causes a butterfly erythema infectiosum (also called Fifth Disease; 'slapped cheek disease') and flu-like symptoms with symmetric polyarthralgias, which usually do not warrant prenatal diagnosis.
Oligoarticular juvenile arthritis is the most common form of juvenile idiopathic arthritis (JIA), representing nearly 50% of cases.
This syndrome has characteristics of profound intellectual deficit in association with microcephaly, short stature, brachydactyly type D, a flattened occiput, downslanting palpebral fissures, low-set large ears, a broad prominent nose and kyphoscoliosis. It has been described in three sisters. The disorder is likely to be transmitted as an autosomal recessive trait.
An autosomal recessive condition caused by mutation(s) in the CTNS gene, encoding cystinosin. It is a sub-type of cystinosis, in which accumulation of cystine in the kidney results in renal dysfunction.
This syndrome has principal characteristics of by Sprengel anomaly (upward displacement of the scapula) and hydrocephaly. Other anomalies such as psychomotor retardation, psychosis, brachydactyly and costovertebral dysplasia may also be present. The syndrome has been described in eight female patients. The mode of transmission has not been firmly established but appears to be either autosomal or X-linked dominant.
A genetic syndrome characterized by the absence of all four limbs.
An extremely rare mostly lethal congenital disorder with characteristics of absence of all four limbs and frequent associated major malformations involving the head, face, eyes, skeleton, heart, lungs, anus, urogenital, and central nervous systems. The syndrome has been described in fewer than 20 patients mainly of Middle Eastern descent.
Thomas syndrome has characteristics of renal anomalies, cardiac malformations and cleft lip or palate. It has been described in six patients. Transmission was suggested to be autosomal recessive.
Infantile-onset autophagic vacuolar myopathy is characterized by increased cardiac and skeletal muscle glycogen with normal acid maltase (GAA; 606800). Skeletal muscle biopsy shows characteristic intracytoplasmic vacuoles that stain for sarcolemmal proteins and complement proteins. Similar pathologic findings are seen in Danon disease (300257), caused by mutation in the LAMP2 gene (309060) on chromosome Xq24, and X-linked myopathy with excessive autophagy (XMEA; 310440), which has been mapped to Xq28.
A rare association of malformations described in only three patients including two siblings. The first patient had profound intellectual deficit and clinical features including short stature, coarse face, deep-set eyes, microphthalmia, large ears, gynoid obesity, imperforate anus, sacral spina bifida, pseudovaginal perineoscrotal hypospadias, persistence of Mullerian structures, and low gonadotrophin levels. His XY sibling was raised as a girl, was slightly mentally impaired and had microphthalmia and large ears and short stature. The third patient had severe hearing loss, ocular colobomata, hypogonadism of central origin, distinct craniofacial features and skeletal anomalies with cervical spina bifida, hyperkyphosis and thoracic deformity. All patients had a normal 46, XY karyotype. Inheritance could be either autosomal recessive or X-linked.
A form of triphalangeal thumb that cannot be placed opposite the fingers of the same hand.
Aniridia-intellectual disability syndrome is an extremely rare autosomal dominant developmental defect of the eye described in several members of one family that is characterized by the association of moderate intellectual disability with aniridia, lens dislocation, optic nerve hypoplasia (see this term) and cataracts. There have been no further descriptions in the literature since 1974.
Craniometaphyseal dysplasia is an osteochondrodysplasia characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that may finally result in hearing loss and facial palsy (summary by Nurnberg et al., 1997). The delineation of separate autosomal dominant (CMDD; 123000) and autosomal recessive forms of CMD by Gorlin et al. (1969) was confirmed by reports that made it evident that the dominant form is relatively mild and comparatively common, whereas the recessive form is rare, severe, and possibly heterogeneous.
Potocki-Lupski syndrome (PTLS) is characterized by cognitive, behavioral, and medical manifestations. Cognitively, most individuals present with global developmental delay, later meeting criteria for moderate intellectual disability. Behaviorally, issues with attention, hyperactivity, withdrawal, and anxiety may be seen. Some individuals meet criteria for autism spectrum disorder. Medically, hypotonia, oropharyngeal dysphagia leading to failure to thrive, congenital heart disease, hypoglycemia associated with growth hormone deficiency, and mildly dysmorphic facial features are observed. Medical manifestations typically lead to identification of PTLS in infancy; however, those with only behavioral and cognitive manifestations may be identified in later childhood.
A rare evolutive vascular malformation disorder characterised by closely clustered irregular dilated capillaries that can be asymptomatic or that can cause variable neurological manifestations such as seizures, non-specific headaches, progressive or transient focal neurologic deficits, and/or cerebral haemorrhages. To date, mutations in three genes have been demonstrated; KRIT1, CCM2 and PDCD10, located on chromosome 7q21.2, 7p13, and 3q26.1 respectively, which encode proteins that, among their various functions, modulate junction formation between vascular endothelial cells. Transmitted as an autosomal dominant trait with incomplete penetrance.
Syndrome with characteristics of unusual facial features, microcephaly, developmental delay, and severe postnatal growth retardation. It has been reported in two brothers born to normal parents. Additional features include hypogonadism, flexion contractures, hypoplastic patella, scoliosis, eczema and recurrent infections. The characteristic facies were marked by sloping forehead, beaked nose, large protruding ears and micrognathia. Low levels of serum gammaglobulins and defective chemotaxis were detected in both boys during infancy.
An extremely rare multiple congenital abnormality syndrome, described in only three brothers to date, with the association of congenital cataract, sensorineural deafness, hypogonadism, mild intellectual deficit, hypertrichosis, and short stature. There have been no further descriptions in the literature since 1995.
Describes the combination of two or more of the following anomalies: neural tube defects (e.g. anencephaly, encephalocele, spina bifida cystica), cleft lip and palate, omphalocele and congenital diaphragmatic hernia . These anomalies are associated at a higher frequency than would be expected with random combination rates.
Syndrome that has characteristics of loss of subcutaneous fat layers on the limbs, lipodystrophy in the face and trunk and scleroderma-like skin disorders (thickened skin on the palms and soles and skin pigment changes on the limbs and trunk). The syndrome has been described in only one family with three affected siblings. Other clinical signs are joint contractures, reduced relative body weight, a bird-like facial appearance with a beaked nose, and micrognathia. One sibling also showed insulin-resistant diabetes mellitus. The syndrome is due to a combined decreased action of insulin, insulin-like growth factor I (IGF-1) and epidermal growth factor (EGF). The disease shows common clinical characteristics with Werner syndrome.
An extremely rare syndrome described in less than 20 families to date and has characteristics of total or partial alopecia associated with intellectual deficit. The syndrome can be associated with other anomalies such as seizures, sensorineural hearing loss, delayed psychomotor development, and/or hypertonia.
This syndrome has characteristics of hypergonadotropic hypogonadism, intellectual deficit, and congenital skeletal anomalies involving the cervical spine and superior ribs, and diabetes mellitus. It has been described in two brothers. Testicular biopsy revealed germinal aplasia and complete seminiferous tubular fibrosis.
A distal myopathy with characteristics of weakness in the distal upper extremities usually finger and wrist extensors which later progresses to all hand muscles and distal lower extremities primarily in toe and ankle extensors. This disease is mainly restricted to a geographical area around the Baltic Sea and is a late adult-onset disorder. Caused by a missense change (c.1362G>A; p.E384K) in TIA1 gene (2p13) which encodes nucleolysin TIA-1 isoform p40, a key component of stress granules. Inherited as an autosomal dominant trait.
A chronic neurodegenerative disorder with features of spastic paraparesis (beginning at about 10 years of age) and hearing deficits. It has been described in affecting at least six male members spanning three generations of a large family. Some relatives presented with tremor, cataracts, sensory deficits, short stature, hypogonadism, elevated cerebrospinal fluid protein, and/or absent or prolonged somatosensory evoked potentials.
A platelet granule disorder with manifestation of thrombocytopenia, increased mean platelet volumes, decreased platelet responsiveness to aggregating agents and significant defects in platelet ultrastructural morphology leading to prolonged bleeding times and bleeding.
This syndrome has characteristics of partial pancreatic agenesis, diabetes mellitus, and heart anomalies (including transposition of the great vessels, ventricular or atrial septal defects, pulmonary stenosis, or patent ductus arteriosis). It has been described in one Japanese family, in which the mother and at least two of her four children were affected (another two children died shortly after birth). The syndrome appears to be inherited as an autosomal dominant trait.
A rare multiple congenital anomalies syndrome with characteristics of relative macrocephaly, pectus excavatum, short stature, nail dysplasia, and motor developmental delay (that resolves during childhood). There have been no further descriptions in the literature since 1992.
The subclinical or symptomatic stage of syphilis, occurring at an average of three weeks after contact with an infected individual. It manifests with one or more painless, indurated ulcers (chancres) of the skin or mucous membranes at the site of inoculation. These lesions heal spontaneously within a few weeks.
An extremely rare type of heart-hand syndrome. Described in two families to date, with characteristics of upper limb malformations (brachytelephalangy type D, hypoplastic deltoids, mild shortening of the fourth and fifth metacarpals in some individuals, skeletal anomalies in the humerus, radius, ulnae, and thenar bones) and cardiac arrhythmias (junctional rhythms and atrial fibrillation).
A rare chromosomal anomaly syndrome with a highly variable phenotype. Principle characteristics are prenatal and postnatal growth delay, mild to severe intellectual disability, hemiatrophy, webbed neck, ocular and cutaneous pigmentary anomalies, craniofacial dysmorphic features (microcephaly, upslanted palpebral fissures, ptosis, ear malformations, flat nasal bridge, micrognathia) and cardiac abnormalities (including ventricular and atrial septal defect, pulmonary or aortic stenosis). Hearing loss and limb malformations (cubitus valgus, syn/brachydactyly), renal and genital anomalies have also been reported.
Characteristic features of the distal 3p- syndrome include low birth weight, microcephaly, trigonocephaly, hypotonia, psychomotor and growth retardation, ptosis, telecanthus, downslanting palpebral fissures, and micrognathia. Postaxial polydactyly, renal anomalies, cleft palate, congenital heart defects (especially atrioventricular septal defects), preauricular pits, sacral dimple, and gastrointestinal anomalies are variable features. Although intellectual deficits are almost invariably associated with cytogenetically visible 3p deletions, rare patients with a 3p26-p25 deletion and normal intelligence or only mild abnormalities have been described (summary by Shuib et al., 2009).
A rare chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 3. Phenotype can be highly variable, but it primarily has characteristics of significant developmental delay, postnatal growth above the mean, muscular hypotonia and distinctive facial features (such as broad and prominent forehead, hypertelorism, epicanthic folds, ptosis, short philtrum, protruding lips with a full lower lip, high arched palate). Abnormal hypoplastic male genitalia and skeletal abnormalities are frequently present.
Spastic paraplegia 3A (SPG3A) is a hereditary spastic paraplegia (HSP) characterized by progressive bilateral and mostly symmetric spasticity and weakness of the legs, diminished vibration sense caused by degeneration of the corticospinal tracts and dorsal columns, and urinary bladder hyperactivity. The average age of onset is four years. More than 80% of reported individuals manifest spastic gait before the end of the first decade of life. Most persons with early-onset SPG3A have a ""pure"" (""uncomplicated"") HSP; however, complicated HSP with axonal motor neuropathy and/or distal amyotrophy with lower motor neuron involvement (Silver syndrome phenotype) have been observed. The rate of progression in SPG3A is slow, and wheelchair dependency or need for a walking aid (cane, walker, or wheelchair) is relatively rare.
Tibia absent - polydactyly - arachnoid cyst syndrome is a very rare constellation of multiple anomalies, including absence or hypoplasia of the tibia.
Hearing loss-familial salivary gland insensitivity to aldosterone syndrome is characterised by bilateral moderate-to-severe sensorineural hearing loss and salivary gland insensitivity to aldosterone resulting in hyponatremia. It has been described in two brothers. Transmission appeared to be autosomal recessive.
Umbilical cord ulceration-intestinal atresia syndrome is characterised by congenital intestinal atresia, umbilical cord ulceration and severe intrauterine haemorrhage.
A multiple congenital anomaly disorder with characteristics of anonychia congenita totalis and microcephaly, with normal intelligence along with some minor anomalies including single transverse palmar creases, fifth-finger clinodactyly and spaced teeth. Inheritance is likely to be autosomal recessive.
This syndrome is characterised by primary hypergonadotropic hypogonadism and partial alopecia. So far, it has been described in seven patients from three families. Mullerian hypoplasia, absent or streak ovaries, hypoplastic internal genitalia and primary amenorrhoea were described in the females. The male appeared to have germinal cell aplasia. All patients displayed partial scalp alopecia, and axillary and pubic hair was sparse or absent in the females but normal in the male patient. Additional findings in some of the female patients included sparse eyebrows, microcephaly, flat occiput, dorsal kyphosis and mild intellectual deficit. Transmission was autosomal recessive.
Fusion of the mandibular condyle to the base of the skull, resulting in limitation of jaw opening.
This syndrome has characteristics of intellectual deficit, seizures and psoriasis. It has been described in four male cousins. The mode of inheritance is thought to be X-linked recessive.
Moyamoya disease is a disorder of blood vessels in the brain, specifically the internal carotid arteries and the arteries that branch from them. These vessels, which provide oxygen-rich blood to the brain, narrow over time. Narrowing of these vessels reduces blood flow in the brain. In an attempt to compensate, new networks of small, fragile blood vessels form. These networks, visualized by a particular test called an angiogram, resemble puffs of smoke, which is how the condition got its name: ""moyamoya"" is an expression meaning ""something hazy like a puff of smoke"" in Japanese.Moyamoya disease commonly begins either around age 5 or in a person's thirties or forties. A lack of blood supply to the brain leads to several symptoms of the disorder, including temporary stroke-like episodes (transient ischemic attacks), strokes, and seizures. In addition, the fragile blood vessels that grow can develop bulges (aneurysms), or they can break open, leading to bleeding (hemorrhage) in the brain. Affected individuals may develop recurrent headaches, involuntary jerking movements (chorea), or a decline in thinking ability. The symptoms of moyamoya disease often worsen over time if the condition is not treated.Some people have the blood vessel changes characteristic of moyamoya disease in addition to features of another disorder, such as neurofibromatosis type 1, sickle cell disease, or Graves disease. These individuals are said to have moyamoya syndrome.
This syndrome has main feature of congenital cataracts with squint, intellectual deficit, anomalies of the genitourinary tract (rectovesical fistula, micropenis, undescended testis, and hypospadias), imperforate anus and other anomalies. It has been described in three siblings born to nonconsanguineous parents. It is likely to be transmitted as an autosomal recessive trait.
A multiple congenital developmental anomalies syndrome with characteristics of arachnodactyly of fingers and toes associated with craniofacial dysmorphism (including abnormal cranial ossification, frontal bossing, flat calvaria, shallow deformed orbits resulting in exophthalmos, midface hypoplasia and micrognathia), feeding difficulties in infancy, infantile muscular hypotonia, and developmental delay leading to intellectual disability.
A rare genetic disease reported in two siblings of consanguineous Arab parents with characteristics of cystic fibrosis, gastritis associated with Helicobacter pylori, folate deficiency megaloblastic anaemia, and intellectual disability. There have been no further descriptions in the literature since 1991.
Acortico-subcortical suprabulbar or pseudobulbar palsy of the lower cranial nerves, with characteristics of severe dysarthria and dysphagia associated with bilateral central facio-pharyngo-glosso-masticatory paralysis, with prominent automatic-voluntary dissociation in which involuntary movements of the affected muscles are preserved. Less than 150 cases have been described in the literature so far. Can occur at any age. Patients have severe speech disturbances and most are mute.Chewing and swallowing are severely impaired. Caused by developmental or acquired bilateral lesions of the anterior opercula. In children, it presents congenitally (bilateral opercular polymicrogyria) or as an acquired disorder due to encephalitis, epilepsy and neurodegenerative disorders. The syndrome is generally sporadic but some familial cases have been described.
A rare and crippling chondrodysplasia, reported mainly in the Maputaland region in northern Kwazulu Natal, South Africa, with features of bilateral and uniform arthropathy of the joints that primarily and most severely affects the hip but that can also affect many other joints. Manifests with pain and stiffness that progressively limits joint movement, eventually compromising a patient's ability to walk. Severe short stature and brachydactyly has been reported in a few patients with the disorder.
Syndrome that is characterised by the association of conotruncal heart defects, myelomeningocoele and craniofacial dysmorphism similar to that seen in monosomy 22q11. Only five cases have been reported in the literature. The identification, by FISH, of 22q11.2 deletions in the majority of reported cases (including the original cases described by Kousseff) indicated that this syndrome is part of the variable clinical spectrum of monosomy 22q11. However, the absence of a 22q11.2 deletion in one patient suggests Kousseff syndrome to be a causally heterogeneous disorder.
An extremely rare malformative association, described in only two siblings to date with characteristics of Hirschsprung disease (defined by the presence of an aganglionic segment of variable extent in the terminal part of the colon that leads to the symptoms of intestinal obstruction including constipation and abdominal distension), polydactyly of hands and/or feet, unilateral renal agenesis, hypertelorism and congenital deafness. There have been no further descriptions in the literature since 1988.
Syndrome that was described in two siblings born to consanguineous parents in 1985 with the presence of 15 dorsal vertebrae and rib pairs. No other cases have been documented since the initial report.
Prosopagnosia is the inability to recognize someone by the face alone, in the absence of sensory or intellectual impairment (Schwarzer et al., 2007). Almost all reported cases are of the acquired form, but there is evidence for a familial form as well (McConachie, 1976; de Haan, 1999; Galaburda and Duchaine, 2003; Kennerknecht et al., 2006).
Cardiospondylocarpofacial syndrome is characterized by growth retardation, dysmorphic facial features, brachydactyly with carpal-tarsal fusion, extensive posterior cervical vertebral synostosis, cardiac septal defects with valve dysplasia, and deafness with inner ear malformations (Le Goff et al., 2016).
Polycystic ovaries-urethral sphincter dysfunction syndrome is characterised by urinary retention and incomplete emptying of the bladder associated with abnormal electromyographic activity. It has been described in 33 women, 14 of whom also had polycystic ovaries.
Syndrome that is characterised by cataracts, otitis media, intestinal malabsorption, chronic respiratory infection and failure to thrive. It has been recently described in two siblings born to consanguineous parents. The patients also developed recurrent pneumonia and progressive azotaemia leading to end-stage renal disease. Both children died of overwhelming infection (sepsis, meningitis). An autosomal recessive mode of inheritance was proposed.
A variant of neurofibromatosis type 1 characterised by the combination of features of neurofibromatosis type 1, such as café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, optic nerve glioma and multiple neurofibromas; and Noonan syndrome, with features such as short stature, typical facial features, congenital heart defects and unusual pectus deformity.
Pili torti-onychodysplasia is a form of ectodermal dysplasia characterised by dystrophy of the distal part of the nails and trichodysplasia. It has been described in only one family. Transmission is autosomal recessive.
A rare genetic ectodermal dysplasia syndrome with characteristics of sparse, thin brittle scalp hair as well as sparse eyebrows, eyelashes, axillary and pubic hair, delayed eruption of deciduous teeth and hypodontia of both dentitions. Mild palmoplantar keratosis, cafe au lait spots on back, mild dystrophy of nails and tibial deflection of toes are also associated. There have been no further descriptions in the literature since 1986.
A very rare genetic disorder characterized by cleft lip and palate, sparse scalp hair, and partial syndactyly of the fingers and toes.
Impaired mental functioning occurs as an isolated feature or as part of many syndromes listed in the X-linked catalog. Mental retardation that is not associated with other distinguishing features is referred to as 'nonspecific.' Classification Opitz and Sutherland (1984) reported on a conference in which fragile X mental retardation and X-linked mental retardation of numerous other types were discussed. The report contains a rather comprehensive discussion by Opitz of the nosology of X-linked mental retardation. Mulley et al. (1992) reviewed nomenclature guidelines for X-linked mental retardation. Raymond (2006) reviewed the diagnosis and classification of X-linked mental retardation and discussed the phenotypes associated with genes causing syndromic and nonsyndromic mental retardation.
Syndrome with characteristics of corneal epithelial changes (associated with photophobia and burning and watering of the eyes), diffuse palmoplantar hyperkeratosis, distal onycholysis, brachydactyly, short stature, dental problems and premature birth. It has been described in seven individuals from three generations of one family. It is transmitted as an autosomal dominant trait.
An autosomal recessive liver disease, which was associated with numerical dental aberrations in a consanguineous Arabia Saudi family. This association suggests that the same gene is involved in both defects. General hypomineralisation and enamel hypoplasia found in this family is thought to be secondary to malabsorption due to liver disease.
An extremely rare syndrome with characteristics of multiple unerupted permanent teeth, hypoplasia of the alveolar process and of the maxillo-zygomatic region, severe genu valgum and deformed ears. Consanguinity in the family suggested autosomal recessive inheritance.
Syndrome with characteristics of intellectual deficit, mild dysmorphism, type A brachydactyly, signs of obesity and ankylosis of both thumbs. It has been reported in several females from one family (a girl and her mother, her grandmother and probably also her sister and her great-aunt), as well as in an isolated case.
This syndrome has characteristics of severe intellectual deficit, brachycephaly, plagiocephaly, prominent forehead and coarse facial features. It has been described in two males from one family. Two females belonging to the same family displayed moderate intellectual deficit but no craniofacial dysmorphism.
A plasmacytoma characterized by the presence of malignant cells with anaplastic features.
A variant of gastrointestinal stromal tumor with ultrastructural features of neural differentiation. It is composed of spindle or epithelioid neoplastic cells.
This syndrome has characteristics of facial dysmorphism (hypertelorism, telecanthus, downslanting palpebral fissures, ptosis, malar hypoplasia, broad nasal bridge, thin upper lip, smooth philtrum, and low-set prominent ears) and associated with joint anomalies (genu valgum or cubitus valgus, hyper-extensible joints). It has been described in two patients (a mother and her son). The boy also had hypoplastic shawl scrotum and cryptorchidism, and the mother had mild intellectual deficit.
Extremely rare syndrome with features of microcephaly and brachycephaly, eye anomalies (microphthalmia, microcornea, congenital cataract), hypogenitalism, severe intellectual deficit, growth retardation and progressive spasticity. This syndrome is transmitted as an X-linked trait.
Microcephaly-seizures-intellectual disability-heart disease syndrome is characterised by intellectual deficit, a cardiac anomaly, micropenis, hypothyroidism, epileptic seizures, and skeletal anomalies. It has been described in two males.
Microcornea-corectopia-macular hypoplasia syndrome is characterised by microcornea, which may also be accompanied by corectopia and macular hypoplasia. It has been described in three individuals from two successive generations of one family.
Spontaneous periodic hypothermia (SPH) is a neurological disorder characterized by spontaneous periodic hypothermia and hyperhidrosis in the absence of hypothalamic lesions.
Eng-Strom syndrome is characterised by intrauterine growth retardation and intermittent locking of the finger joints. It has been described in two individuals: a mother and her daughter. The mode of transmission is autosomal dominant.
A multiple congenital anomalies/dysmorphic syndrome with characteristics of intellectual disability, postaxial polydactyly, phalangeal hypoplasia, 2-3 toe syndactyly, uncombable hair and facial dysmorphism (including frontal bossing, hypotelorism, narrow palpebral fissures, nasal bridge and lips, prominent nasal root, large abnormal ears with prominent antihelix, poorly folded helix, underdeveloped lobule and antitragus, and micrognathia evolving into prognathism). Cryptorchidism, conductive hearing loss and progressive thoracic kyphosis were also reported.
Describes the extremely rare triad of dilated cardiomyopathy, premature cataract and articular disease of the hips and spine with characteristics of hip joint degeneration, irregular intervertebral discs and platyspondyly. The ocular abnormalities are often the first symptoms to arise. There have been no further descriptions in the literature since 1985.
Syndrome with characteristics of telecanthus, hypertelorism, strabismus, pes cavus and other variable anomalies. It has been described in a father and his son. The son also had hypospadias, bilateral inguinal hernia, clinodactyly and camptodactyly of the fingers. Radiographic findings including flared metaphyses of the long bones and osteopenia.
A rare intellectual disability syndrome characterised by pre and postnatal growth deficiency, generalised muscular hypotonia, developmental delay (particularly of speech and language), hypotrophy of distal extremities, small and puffy hands and feet, eczematous skin and dental anomalies (i.e. small, widely-spaced teeth). Partial agenesis of the corpus callosum and a selective immunoglobulin IgG2 subclass deficiency has also been reported in some patients.
Deletion 5q35 refers to the different congenital malformation syndromes resulting from deletions of variable extent of the terminal part of the long arm of chromosome 5 (5q), spanning the region from 5q35.1 to 5q35.3 . The most significant anomaly is a recurring deletion in 5q35.2 comprising the NSD1 gene that causes Sotos syndrome. Subtelomeric deletions of the terminal 3.5 Mb region on 5q35.3 are very rare. Larger deletions including bands 5q35.1, 5q35.2 and 5q35.3 cause a more severe phenotype that associates severe developmental delay with microcephaly and significant cardiac defects. Various combinations of signs may result from deletions of variable extent depending on the genes comprised in the deleted segment.
Syndrome with the association of moderate to severe intellectual deficit, microcephaly, epilepsy, coarse face, hirsutism and skeletal abnormalities (scoliosis and retarded bone development). It has been described only once, in two siblings (one male and one female). This syndrome is likely to be an autosomal recessive condition and thus parents should be informed of a 25% risk of recurrence for other children.
Syndrome with characteristics of progressive joint stiffness, glaucoma, short stature and lens dislocation. It has been described in three members of a family (the grandfather, his daughter and grandson). It is likely to be transmitted as an autosomal dominant trait. The acronym GEMSS (Glaucoma, Ectopia, Microspherophakia, Stiff joints, Short stature) was proposed as a name for the syndrome.
A movement disorder with manifestation of episodes of involuntary tremor of the chin and lower lip. The disorder has been described in less than 25 families from Europe and the USA, with a slight male preponderance. Onset usually occurs in childhood and may be precipitated by stress and emotion. Episodes may occur during sleep. There are no associated neurological abnormalities. Spontaneous improvement with age is possible. Inheritance is autosomal dominant.
Systemic sclerosis that is diagnosed in children. Juvenile systemic sclerosis is more likely to be of the overlap variant and presents with musculoskeletal involvement.
Syndrome with characteristics of caudal appendage, short terminal phalanges, deafness, cryptorchidism, intellectual deficit, short stature and dysmorphism. It has been described in monozygotic twin boys.
This syndrome has characteristics of macrocephaly and midface hypoplasia, intellectual deficit, short stature, spastic paraplegia and severe central nervous system anomalies (hydrocephalus and Dandy-Walker malformation). It has been described in two unrelated adults.
A type of Macrodactyly affecting one or several toes.
A rare chromosomal anomaly syndrome with a variable phenotype. Manifestations range from clinically normal to patients presenting intrauterine growth retardation, congenital heart anomalies (mainly ventricular septal defect), multiple dysmorphic features (hypertelorism, prominent nasal bridge) and other congenital anomalies (including eventration of diaphragm, agenesis of corpus callosum, cloverleaf skull, clinodactyly, anteriorly placed anus). Psychomotor development may be normal in spite of low growth parameters being associated.
A rare developmental defect during embryogenesis syndrome with characteristics of congenital manifestations of both oculo-auriculo-vertebral spectrum and caudal regression sequence. Phenotype is highly variable but patients typically present facial dysmorphism (including asymmetry, hypertelorism), auricular abnormalities (for example preauricular tags, microtia, absence of middle ear ossicles), skeletal malformations (hemivertebrae, hip dislocation, sacral agenesis/dysplasia, talipes equinovarus, flexion deformity of lower limbs), cardiac defects (dextrocardia, septal defects), renal and genitourinary anomalies (such as renal agenesis/dysplasia, abnormal external genitalia) along with anal anomalies such as anal atresia and rectovesical fistula.
A complex form of hereditary spastic paraplegia with characteristics of delay in motor development followed by a slowly progressive spastic paraplegia (affecting mainly lower extremities) associated with a desquamating facial rash with butterfly distribution (presenting at around two months of age) and dysarthria. There have been no further descriptions in the literature since 1982.
A group of diseases arising from pregnancy that are commonly associated with hyperplasia of trophoblasts (TROPHOBLAST) and markedly elevated human CHORIONIC GONADOTROPIN. They include HYDATIDIFORM MOLE, invasive mole (HYDATIDIFORM MOLE, INVASIVE), placental-site trophoblastic tumor (TROPHOBLASTIC TUMOR, PLACENTAL SITE), and CHORIOCARCINOMA. These neoplasms have varying propensities for invasion and spread.
A rare chromosomal anomaly syndrome with a highly variable phenotype. Manifestations include Blaschko linear skin pigmentary dysplasia, body asymmetry, enamel dysplasia, and developmental and growth delay. Intellectual disability, facial dysmorphism (frontal bossing, abnormal palpebral fissures, strabismus, abnormally shaped ears and micrognathia) and genital anomalies (undescended testes) have also been observed. It has been reported to be associated with maternal uniparental disomy of chromosome 7, resulting in a Silver-Russell syndrome phenotype. Cases with no associated malformations have also been reported.
Chromosome 8-derived supernumerary ring/marker is a rare chromosomal anomaly comprising variable parts of chromosome 8. The phenotype of mosaic or non-mosaic supernumerary r(8)/mar(8) ranges from almost normal to variable degrees of minor abnormalities, and growth and mental retardation overlapping with the well-known mosaic trisomy 8 syndrome (see this term).
A partial deletion of the short arm of chromosome 8 with manifestations of low birth weight, postnatal growth deficiency, mild intellectual deficit, hyperactivity, craniofacial abnormalities, and congenital heart defects. The prevalence is unknown but 8p23.1 deletions are rare. The clinical manifestations are variable and do not depend on the size of the deletion, since this is the same in the majority of patients. Most 8p23.1 deletions occur de novo, however, parents can carry and transmit the chromosomal rearrangement to their children as well, with a risk of 50% for each child.
A rare systemic inflammatory disease associated with long-lasting biopersistance of post-vaccinal aluminic granulomas. More than 600 cases have been reported to date, most of them in France. This is probably due to large-scale vaccination with aluminium-containing vaccines in France during the 1990s. The disease generally manifests with myalgias of variable intensity, and is usually associated with weakness and chronic fatigue. Belongs to the group of Autoimmune/inflammatory Syndromes Induced by Adjuvants (ASIA): it is triggered, probably in genetically predisposed patients, by injection of vaccines containing aluminium hydroxide and may occur up to 10 years following vaccination.
A neoplastic process characterized by diffuse overgrowth of mature adipose tissue.
A rare congenital syndrome characterised by skin and hair hypopigmentation, growth retardation, and intellectual deficit that are associated with a combination of various additional clinical anomalies such as ocular albinism, cataract, delayed neuropsychomotor development, sensorineural hearing loss, dolicocephaly, high arched palate, widely spaced teeth, anaemia, and/or nystagmus.
This syndrome has characteristics of sensorineural deafness, bilateral synostosis of the fourth and fifth metacarpals and metatarsals, genital anomalies (hypospadias in males), psychomotor delay and abnormal dermatoglyphics. So far, it has been described in two unrelated patients. Facial dysmorphism was noted in both patients (prominent forehead, ear anomalies, facial asymmetry and an open mouth appearance).
Syndrome with characteristics of growth retardation, intellectual deficit, preaxial polydactyly and colobomatous anomalies. It has been described in one pair of siblings (brother and sister). The mode of transmission is thought to be autosomal recessive.
A very rare epidermal naevus disorder characterised by the association of speckled lentiginous nevi with epidermal sebaceous nevi and extracutaneous anomalies.
Syndrome with the presence of microcephaly and intracranial calcifications at birth accompanied by neurological delay, seizures and a clinical course similar to that seen in patients after intrauterine infection with Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex (so-called TORCH syndrome), or other agents, despite repeated tests revealing the absence of any known infectious agent. The clinical presentation of the reported cases is rather heterogeneous with variable manifestations including intrauterine growth retardation, hepatosplenomegaly, cerebellar hypoplasia or atrophy and congenital cataract. The cause remains unknown. Several familial cases, compatible with an autosomal recessive pattern of inheritance have been described.
This syndrome is characterised by variable spastic paraplegia, bilateral sensorineural deafness, intellectual deficit and progressive nephropathy.
An extremely rare multiple congenital anomaly syndrome with characteristics of distinctive intrauterine growth retardation, skeletal dysplasia with multiple malformations including camptodactyly of all fingers, bilateral hallux valgus, short second, fourth and fifth toes, hypoplastic patella, microcephaly, low-set ears, short neck, cuboid-shaped vertebral bodies, pectus excavatum, hip dislocation, and hypoplastic pubic region and genitalia. Described in two sisters there have been no further descriptions in the literature since 1985.
Camptodactyly-taurinuria syndrome is a congenital malformation syndrome characterized by the association of a permanent camptodactyly of the fingers (see this term) with the over excretion of taurine in the urine. Camptodactyly mainly affects the little finger, although any finger may be involved. The disease has been described in 17 affected patients from 4 unrelated families. An autosomal dominant inheritance has been suggested. There have been no further descriptions in the literature since 1966.
A rare chronic immune-mediated demyelinating polyneuropathy. The exact prevalence is unknown but less than 30 cases have been reported in the literature. The clinical picture comprises a chronic neuropathy with marked sensory ataxia and areflexia, and with relatively preserved motor function in the limbs. Motor weakness affecting the oculomotor and bulbar muscles is present as either a fixed or relapsing-remitting feature.
Syndrome with the association of hypogonadism due to primary gonadal failure, mitral valve prolapse, mild intellectual deficit and short stature. It has been described in two brothers. Growth hormone levels and the response to gonadotropin stimulation tests were also abnormal.
Myotonic dystrophy type 2 (DM2) is characterized by myotonia (90% of affected individuals) and muscle dysfunction (weakness, pain, and stiffness) (82%), and less commonly by cardiac conduction defects, iridescent posterior subcapsular cataracts, insulin-insensitive type 2 diabetes mellitus, and testicular failure. Although myotonia (involuntary muscle contraction with delayed relaxation) has been reported during the first decade, onset is typically in the third decade, most commonly with fluctuating or episodic muscle pain that can be debilitating and weakness of the neck flexors and finger flexors. Subsequently, weakness occurs in the elbow extensors and the hip flexors and extensors. Facial weakness and weakness of the ankle dorsiflexors are less common. Myotonia rarely causes severe symptoms.
A rare chromosomal anomaly syndrome with principle characteristics of intrauterine growth restriction, congenital cardiac anomalies (ventricular and atrial septal defects, patent ductus arteriosus) and craniofacial dysmorphism (hypertelorism, downslanting palpebral fissures, wide nasal bridge). Patients also present brain (hypoplastic cerebellum, ventricular asymmetry), renal (small dysplastic kidneys), and/or genital (undescended testis, small penis, hypoplastic labia majora) anomalies. Digital and skin pigmentation abnormalities have also been reported.
The features of frontofacionasal dysplasia include blepharophimosis, lower lid lagophthalmos, primary telecanthus, S-shaped palpebral fissues, facial hypoplasia, eyelid coloboma, widow's peak, cranium bifidum occultum, frontal lipoma, nasal hypoplasia, deformed nostrils, bifid nose, and cleft of lip, premaxilla, palate, and uvula (White et al., 1991). Also see frontonasal dysplasia (136760).
This syndrome is characterised by the association of hypogonadotropic hypogonadism (with primary amenorrhoea and lack of secondary sexual development) and retinitis pigmentosa. It has been described in two sisters born to nonconsanguineous parents.
Distal trisomy of the long arm of chromosome 10 results in characteristics of pre and postnatal growth retardation, a pattern of specific facial features, hypotonia, and developmental and psychomotor delay. To date, approximately 40 cases have been reported. Most cases are diagnosed in infancy or in childhood. The range and severity of symptoms and physical findings may vary from case to case, depending upon the exact length and location of the duplicated portion of chromosome 10q. The duplicated region almost always includes 10qter, with the most frequent proximal breakpoint at 10q24 (with variation from q22 to q25). Interstitial duplications of 10q have also been reported.
This syndrome has characteristics of major seizures, dysmorphic features (round face, bulbous nose, wide mouth, prominent philtrum), pes planus, psychomotor retardation and obesity. It has been described in five children (three boys and two girls, one of whom died in infancy) from two unrelated Mexican families.
An ectodermal dysplasia syndrome with characteristics of severe arthrogryposis, multiple ectodermal dysplasia features, cleft lip/palate, facial dysmorphism, growth deficiency and a moderate delay of psychomotor development. Ectodermal dysplasia manifestations include sparse, brittle and hypopigmented hair, xerosis, multiple nevi, small conical shaped teeth and hypodontia, and facial dysmorphism with blepharophimosis, deep-set eyes and micrognathia.
The spectrum of isolated sulfite oxidase deficiency ranges from classic early-onset (severe) disease to late-onset (mild) disease. Classic ISOD is characterized in the first few hours to days of life by intractable seizures, feeding difficulties, and rapidly progressive encephalopathy manifest as abnormal tone (especially opisthotonus, spastic quadriplegia, and pyramidal signs) followed by progressive microcephaly and profound intellectual disability. Lens subluxation or dislocation, another characteristic finding, may be evident after the newborn period. Children usually die during the first few months of life. Late-onset ISOD manifests between ages six and 18 months and is characterized by ectopia lentis (variably present), developmental delay/regression, movement disorder characterized by dystonia and choreoathetosis, ataxia, and (rarely) acute hemiplegia due to metabolic stroke. The clinical course may be progressive or episodic. In the episodic form encephalopathy, dystonia, choreoathetosis, and/or ataxia are intermittent.
A multiple congenital anomaly syndrome described in 5 patients to date. Characteristics include flat face, hypertelorism, flat occiput, upward slanting palpebral fissures, cleft palate, micrognathia, short neck, and severe congenital heart defects, which were lethal in 3 of the 5 patients. Malrotation of the intestine, bilateral clinodactyly, bilobed tongue, short fourth metatarsals and bifid thumbs were reported in individual cases. There have been no further descriptions in the literature since 1997.
Acquired angioedema (AAE) is characterized by the occurrence of transitory and recurrent subcutaneous and/or submucosal edemas resulting in swelling and/or abdominal pain due to an acquired C1 inhibitor (C1-INH) deficiency.
Absence of the corpus callosum with unusual facial appearance, mental deficiency, duplication of the halluces, and polydactyly.
The Catania type of acrofacial dysostosis is characterized by intrauterine growth retardation, short stature, microcephaly, intellectual disability, widow's peak, mandibulofacial dysostosis without cleft palate, ear anomalies, mild pre- and postaxial limb hypoplasia with brachydactyly, mild interdigital webbing, dental anomalies, and cryptorchidism and hypospadias in males (Opitz et al., 1993; Wulfsberg et al., 1996).
An extremely rare syndrome with synostosis described in about 4 patients to date with clinical manifestations including congenital unilateral radioulnar synostosis, generalised hypotonia, developmental delay and dysmorphic facial features (long face, prominent nose and ears).
Amelogenesis imperfecta and gingival fibromatosis syndrome is an autosomal recessive condition characterized by mild gingival fibromatosis and dental anomalies, including hypoplastic amelogenesis imperfecta, intrapulpal calcifications, delay of tooth eruption, hypodontia/oligodontia, pericoronal radiolucencies, and unerupted teeth (Martelli-Junior et al., 2008).
An exceedingly rare association with characteristics of cleft lip and progressive retinopathy.
A rare chromosomal anomaly syndrome with a highly variable phenotype. The principle characteristics are growth delay, craniofacial dysmorphism (including prominent forehead, hypertelorism, upslanting palpebral fissures, blepharophimosis, low-set malformed large ears, high arched palate, cleft lip/palate, retrognathia) and cardiac, renal and skeletal (radial ray defects, scoliosis) malformations. Death usually occurs neonatally or in early infancy. Other reported features include central nervous system and ear anomalies, facial clefts and anal atresia.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 11 with high phenotypic variability. Principle characteristics are craniofacial dysmorphism (brachycephaly/plagiocephaly, low-set, posteriorly rotated ears, short philtrum, micrognathia) and intellectual disability. Short stature and seizures, as well as cardiac (atrial septal defect), skeletal (brachy/syndactyly) and genital (micropenis, cryptorchidism) abnormalities may also be associated. Neurodevelopmental anomalies (pain insensitivity, sensorineural hearing loss, expressive language deficiency) and neuropsychiatric disorders (autistic features, auditory hallucination, self-talking) have also been reported.
Ring chromosome 13 is a chromosomal anomaly of chromosome 13 characterized by a widely variable phenotype (ranging from mild to severe) principally characterized by intrauterine growth retardation, developmental delay, short stature, moderate to severe intellectual deficit, microcephaly, facial dysmorphism (i.e. upslanting palpebral fissures, hypertelorism, abnormal ears, broad nasal bridge, high arched palate, micrognathia, small mouth, and thin lips), hands and feet anomalies, and genital abnormalities. Additional features reported include behavioral problems, hearing and speech disorders, congenital heart defects, cerebral malformations, and anal atresia.
Trisomy 18p is an extremely rare chromosomal anomaly with a poorly defined clinical phenotype. Reported manifestations include short stature, mild, moderate or severe developmental delay and intellectual disability, variable but mild facial dysmorphism, and epilepsy.
A chromosomal anomaly consisting of a partial long arm deletion of chromosome 2 with clinical characteristics of a wide range of manifestations (depending on the specific region deleted) which can include seizures, microcephaly, dysmorphic features, cleft palate, eye abnormalities (coloboma, cataract and microphthalmia), growth retardation, failure to thrive, heart defects, limb anomalies, developmental delay and autism.
2q37 deletion syndrome is a condition that can affect many parts of the body. Most babies with 2q37 deletion syndrome are born with weak muscle tone (hypotonia), which usually improves with age. Other neurological abnormalities that are common in affected individuals include mild to severe intellectual disability; delayed development of motor skills, such as sitting and walking; and behavioral problems. About 25 percent of people with this condition have autism spectrum disorder, a developmental condition that affects communication and social interaction.Unusual physical features are also common in people with 2q37 deletion syndrome. About half of affected individuals have unusually short fingers and toes (brachydactyly), often with abnormally short fourth toes that may overlap the other toes. Additional features of this condition may include short stature, obesity, or sparse hair. Many people with 2q37 deletion syndrome have characteristic facial features that can include a prominent forehead, a low frontal hairline, thin eyelids, skin folds covering the inner corner of the eyes (epicanthal folds), outside corners of the eyes that point upward (upslanting palpebral fissures), a small nose, a small mouth with thin lips, a smooth space between the upper lip and nose (smooth philtrum), prominent cheekbones, a large chin, and minor ear abnormalities.Other features of 2q37 deletion syndrome can include seizures and an inflammatory skin disorder called eczema. Some affected individuals have malformations of the brain, heart, gastrointestinal system, kidneys, or genitalia. A few people with 2q37 deletion syndrome develop a rare form of kidney cancer called Wilms tumor.
Progressive weakness and spasticity of the lower limbs due to degeneration of corticospinal axons. Autosomal recessive spastic paraplegia type 11 is a form of complicated spastic paraplegia with neurological features such as mental impairment and thin corpus callosum in addition to spasticity.
Nasopharyngeal carcinoma (NPC, NPCA) is a multifactorial malignancy associated with both genetic and environmental factors. The cancer arises from the epithelium of the nasopharynx. The Epstein-Barr virus has been implicated (Tse et al., 2009). Genetic Heterogeneity of Susceptibility to Nasopharyngeal Carcinoma NPCA1 maps to chromosome 4p. NPCA2 (161550) maps to chromosome 6p21. NPCA3 (617075) is associated with variation in the MST1R gene (600168) on chromosome 3p21. Somatic mutations have been found in the TP53 gene (191170) in nasopharyngeal carcinoma tumors.
In a report on the 37th ENMC Workshop, Rudel and Lehmann-Horn (1997) stated that the sodium channelopathies can be divided into 3 different forms: paramyotonia, potassium-aggravated myotonia, and periodic paralysis. Potassium-aggravated myotonia includes mild myotonia fluctuans, severe myotonia permanens, and acetazolamide-responsive myotonia.
Syndrome with characteristics of progressive pigmentary retinal degeneration (with nyctalopia and visual field restriction), cystic macular degeneration and angle closure glaucoma. It has been described in seven members of one family. Patients also have hyperopia and nanophthalmos. The mode of transmission is autosomal recessive.
Familial hyperinsulinism, also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur (Thornton et al., 1998). Genetic Heterogeneity of Hyperinsulinemic Hypoglycemia HHF2 (601820) is caused by mutation in the KCNJ11 gene (600937) on chromosome 11p15. HHF3 (602485) is caused by mutation in the glucokinase gene (GCK; 138079) on chromosome 7p13. HHF4 (609975) is caused by mutation in the HADH gene (601609) on chromosome 4q25. HHF5 (609968) is caused by mutation in the insulin receptor gene (INSR; 147670) on chromosome 19p13. HHF6 (606762) is caused by mutation in the GLUD1 gene (138130) on chromosome 10q23. HHF7 (610021) is caused by mutation in the SLC16A1 (600682) on chromosome 1p13. There is evidence of further genetic heterogeneity of HHF.
Hyperprolinemia is an excess of a particular protein building block (amino acid), called proline, in the blood. This condition generally occurs when proline is not broken down properly by the body. There are two inherited forms of hyperprolinemia, called type I and type II.People with hyperprolinemia type I often do not show any symptoms, although they have proline levels in their blood between 3 and 10 times the normal level. Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems.Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This form of the disorder has signs and symptoms that vary in severity, and is more likely than type I to involve seizures or intellectual disability.Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of lactic acid in the blood (lactic acidemia) may have hyperprolinemia as well, because lactic acid inhibits the breakdown of proline.
Congenital hypertryptophanemia, which is accompanied by hyperserotonemia, does not appear to have significant clinical consequences (Ferreira et al., 2017).
Neurodegeneration with brain iron accumulation (NBIA, formerly Hallervorden-Spatz syndrome) encompasses a group of rare neurodegenerative disorders characterized by progressive extrapyramidal dysfunction (dystonia, rigidity, choreoathetosis), iron accumulation in the brain and the presence of axonal spheroids, usually limited to the central nervous system.
An inflammatory condition characterised by erythroderma, desquamation, alopecia, chronic diarrhoea, failure to thrive, lymphadenopathy and hepatosplenomegaly associated with severe combined immunodeficiency. The signs and symptoms can evolve over time and may not appear simultaneously. Some patients present with some but not all of these symptoms and may be described as having atypical Omenn syndrome. The syndrome is not caused by a defined genetic defect. The majority of cases reported to date have hypomorphic mutations in RAG1 and RAG2 genes (11p13). Transmission is autosomal recessive.
A syndrome which occurs as a result of the occlusion of one of the vertebral arteries. It may be caused by atherosclerosis, embolism or hemorrhage. Collateral circulation through the circle of Willis is usually comprised as well. Clinical signs may include vertigo, nystagmus, dysarthria, ataxia and sensorimotor deficits. Clinical course may lead to persistence of neurologic deficits. Prognosis is variable with a substantial risk for recurrent infarction.
An orally bioavailable Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. Ruxolitinib specifically binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies.
An orally bioavailable benzamide-type inhibitor of histone deacetylase (HDAC) isoenzymes 1, 2, 3 and 10, with potential antineoplastic activity. Upon administration, tucidinostat binds to and inhibits HDACs, leading to an increase of acetylation levels of histone proteins. This agent also inhibits the expression of kinases in the PI3K/Akt and MAPK/Ras signaling pathways and may result in cell cycle arrest and the induction of tumor cell apoptosis. This may inhibit tumor cell proliferation in susceptible tumor cells. HDACs, a class of enzymes that deacetylate chromatin histone proteins, are upregulated in many tumor types and play key roles in gene expression. Compared to some other benzamide-type HDAC inhibitors, chidamide is more stable, more resistant to degradation and has a longer half-life.
Parathyroid hormone resistance caused by defects in methylation in the GNAS gene that cause loss of expression of Gs-alpha from the maternal allele in renal tissue, resulting in decreased phosphate excretion and increased calcium excretion. Individuals with this condition may also have brachydactyly and partial resistance to thyroid-stimulating hormone.
Pseudohypoparathyroidism (PHP) is a term applied to a heterogeneous group of disorders whose common feature is resistance to parathyroid hormone (PTH; 168450). PHP type II is characterized by a normal cAMP response to PTH infusion, but a deficient phosphaturic response, indicating a defect distal to cAMP generation in renal cells. The clinical features of Albright hereditary osteodystrophy (AHO; see 103580) are not present in PHP II (Mantovani and Spada, 2006). For a general phenotypic description, classification, and a discussion of molecular genetics of pseudohypoparathyroidism, see PHP1A (103580).
An orally bioavailable allosteric inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Akt inhibitor MK2206 binds to and inhibits the activity of Akt in a non-ATP competitive manner, which may result in the inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
An agent targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. Upon intravenous administration, gedatolisib inhibits both PI3K and mTOR kinases, which may result in apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K.
An orally bioavailable inhibitor of cyclin-dependent kinases (CDKs) and tropomyosin receptor kinase A (TRKA), with potential antineoplastic activity. CDK2/TRKA inhibitor PHA-848125 AC potently inhibits cyclin-dependent kinase 2 (CDK2) and exhibits activity against other CDKs including CDK1 and CDK4, in addition to TRKA. Inhibition of these kinases may result in cell cycle arrest and apoptosis of tumor cells that express these kinases. CDKs are serine/threonine kinases involved in regulation of the cell cycle and may be overexpressed in some cancer cell types. The neurotrophin receptor TRKA is mutated in a variety of cancer cell types.
An orally available sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) agonist that acts as a functional antagonist, with potential immunomodulating activity. Upon oral administration, ponesimod selectively binds to S1PR1 on lymphocytes and causes transient receptor activation followed by S1PR1 internalization and degradation. This results in the sequestration of lymphocytes in lymph nodes. By preventing egress of lymphocytes, ponesimod reduces both the amount of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues. This prevents a lymphocyte-mediated immune response. S1PR1, a G-protein coupled receptor, plays a key role in lymphocyte migration from lymphoid tissues.
A third-generation, humanized monoclonal antibody directed against human CD20 with potential antineoplastic activity. Anti-CD20 monoclonal antibody PRO131921 specifically binds to the B cell-specific cell surface antigen CD20. This may result in the induction of a B cell-directed complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) against CD20-expressing B cells leading to B cell apoptosis. CD20 is a non-glycosylated cell surface phosphoprotein which is exclusively expressed on B cells during most stages of B cell development and which is often overexpressed in B-cell malignancies.
The maleate salt form of henatinib, an orally bioavalable, multitargeted tyrosine kinase inhibitor with potential antitumor and antiangiogenic activities. Henatinib inhibits vascular endothelial growth factor receptor type 2 (VEGFR2), a tyrosine kinase receptor upregulated in many tumor cells that plays a key role in angiogenesis. This may result in an inhibition of angiogenesis and eventually tumor cell proliferation. Henatinib, structurally similar to sunitinib, also inhibits, though to a lesser extent, mast/stem cell growth factor receptor (c-Kit) and, platelet-derived growth factor receptor (PDGFR) alpha and beta.
An orally bioavailable inhibitor of histone deacetylases (HDACs) with potential antineoplastic activity. Resminostat binds to and inhibits HDACs leading to an accumulation of highly acetylated histones. This may result in an induction of chromatin remodeling, inhibition of the transcription of tumor suppressor genes, inhibition of tumor cell division and the induction of tumor cell apoptosis. HDACs, upregulated in many tumor types, are a class of enzymes that deacetylate chromatin histone proteins.
A humanized monoclonal antibody (IgG1) raised against amyloid beta peptides with Alzheimer disease treatment application. Solanezumab recognizes and binds the middle amino acid residues 16-24 of the amyloid beta peptide and may be used in a passive immunotherapy treatment.
An antibody-drug conjugate (ADC) consisting of the recombinant anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab conjugated to the maytansinoid DM1 via a nonreducible thioether linkage (MCC) with potential antineoplastic activity. The trastuzumab moiety of this ADC binds to HER2 on tumor cell surfaces; upon internalization, the DM1 moiety is released and binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics and inhibiting cell division and the proliferation of cancer cells that overexpress HER2. Linkage of antibody and drug through a nonreducible linker has been reported to contribute to the improved efficacy and reduced toxicity of this ADC compared to similar ADCs constructed with reducible linkers.
Obesity due to excessive deposition of INTRA-ABDOMINAL FAT in the abdominal VISCERA and OMENTUM.
An event experienced by an infant or a child that is characterized by some combination of apnea, color change, change in muscle tone, choking, and gagging.
Transient reduction in blood pressure levels immediately after exercises that lasts 2-12 hours. The reduction varies but is typically 5-20 mm Hg when compared to pre-exercise levels. It exists both in normotensive and hypertensive individuals and may play a role in excercise related PHYSIOLOGIC ADAPTATION.
Compounds that are designed to mimic the 3D structure of a natural peptide or protein.
Substances that alter the metabolism of LIPIDS.
An inflammatory process with loss of supporting bone in the tissues surrounding functioning DENTAL IMPLANTS.
A copy number variation that results in reduced GENE DOSAGE due to any loss-of-function mutation. The loss of heterozygosity is associated with abnormal phenotypes or diseased states because the remaining gene is insufficient.
The shrinkage of the foreign body encapsulation scar tissue that forms around artificial implants imbedded in body tissues.
Agents that antagonize the ANGIOTENSIN II TYPE 2 RECEPTOR.
A pathological mechanical process that can lead to hip failure. It is caused by abnormalities of the ACETABULUM and/or FEMUR combined with rigorous hip motion, leading to repetitive collisions that damage the soft tissue structures.
A broad category of multi-ingredient preparations that are marketed for the relief of upper respiratory symptoms resulting from the COMMON COLD; ALLERGIES; or HUMAN INFLUENZA. While the majority of these medications are available as OVER-THE-COUNTER DRUGS some of them contain ingredients that require them to be sold as PRESCRIPTION DRUGS or as BEHIND-THE COUNTER DRUGS.
Highly contagious infectious dermatitis with lesions near the interdigital spaces usually in cattle. It causes discomfort and often severe lameness (LAMENESS, ANIMAL). Lesions can be either erosive or proliferative and wart-like with papillary growths and hypertrophied hairs. DICHELOBACTER NODOSUS and TREPONEMA are the most commonly associated causative agents for this mixed bacterial infection disease.
Diseases that are underfunded and have low name recognition but are major burdens in less developed countries. The World Health Organization has designated six tropical infectious diseases as being neglected in industrialized countries that are endemic in many developing countries (HELMINTHIASIS; LEPROSY; LYMPHATIC FILARIASIS; ONCHOCERCIASIS; SCHISTOSOMIASIS; and TRACHOMA).
Deficiencies or mutations in the genes for the SARCOGLYCAN COMPLEX subunits. A variety of phenotypes are associated with these mutations including a subgroup of autosomal recessive limb girdle muscular dystrophies, cardiomyopathies, and respiratory deficiency.
Autosomal recessive limb-girdle muscular dystrophy-3 affects mainly the proximal muscles and results in difficulty walking. Most individuals have onset in childhood; the disorder is progressive. Other features may include scapular winging, calf pseudohypertrophy, and contractures. Cardiomyopathy has rarely been reported (summary by Babameto-Laku et al., 2011). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
Compounds that disintegrate natural waxy exudates such as EAR WAX.
Condition with a variable constellation of phenotypes due to deletion polymorphisms at chromosome location 22q11. It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. In addition, variable developmental problems and schizoid features are also associated with this syndrome. (From BMC Med Genet. 2009 Feb 25;10:16) Not all deletions at 22q11 result in the 22q11deletion syndrome.
Adjustment of BRAIN WAVES from two or more neuronal groups within or across a brain structure (e.g., cortical and limbic brain structures) to become uniform in EEG oscillation patterns in response to a stimulus. It is interpreted as a brain integration sign during many processes such as learning, memory, and perception and involves reciprocal neural connections.
Vaccines using supra-molecular structures composed of multiple copies of recombinantly expressed viral structural proteins. They are often antigentically indistinguishable from the virus from which they were derived.
The reaction of two molecular entities via oxidation usually catalyzed by a transition metal compound and involving dioxygen as the oxidant.
Conditions affecting individuals with 46,XX karyotype characterized by atypical development of one or more of the following: the gonads, the internal reproductive structures, the external reproductive/genital structures.
Presence of testes in an individual with a 46,XX karyotype, typically associated with translocation of the SRY gene, encoding the transcription factor sex-determining region Y protein, from the paternal Y chromosome to the paternal X chromosome during gametogenesis (SRY-positive). Approximately 15-20% of individuals with 46,XX testicular DSD are SRY-negative. These individuals may have other genetic variations affecting testis determination, such as duplication of the SOX9 gene, which encodes the transcription factor SOX-9.
Congenital conditions of atypical sexual development associated with abnormal sex chromosome constitutions including MONOSOMY; TRISOMY; and MOSAICISM.
A PRENATAL ULTRASONOGRAPHY finding of excessively dense fetal bowel due to MECONIUM buildup.
Agents that improve the ability to carry out activities such as athletics, mental endurance, work, and resistance to stress. The substances can include PRESCRIPTION DRUGS; DIETARY SUPPLEMENTS; phytochemicals; and ILLICIT DRUGS.
Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.
Drugs that bind to and block the activation of ADRENERGIC BETA-3 RECEPTORS.
Occurrence of heart arrest in an individual when there is no immediate access to medical personnel or equipment.
Compounds that suppress or block the plasma membrane transport of GAMMA-AMINOBUTYRIC ACID by GABA PLASMA MEMBRANE TRANSPORT PROTEINS.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.
Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.
Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.
Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.
Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.
An endogenous family of proteins belonging to the serpin superfamily that neutralizes the action of thrombin. Six naturally occurring antithrombins have been identified and are designated by Roman numerals I to VI. Of these, Antithrombin I (see FIBRIN) and ANTITHROMBIN III appear to be of major importance.
Compounds that increase the enzymatic activity of LIPOPROTEIN LIPASE. Lipoprotein lipase activators have a potential role in the treatment of OBESITY by increasing LIPID METABOLISM. Note that substances that increase the synthesis of lipoprotein lipase are not included here.
Compounds that act on PURINERGIC RECEPTORS or influence the synthesis, storage, uptake, metabolism, or release of purinergic transmitters.
Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.
Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.
Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.
Compounds that bind to and stimulate PURINERGIC P2X RECEPTORS. Included under this heading are agonists for specific P2X receptor subtypes.
Compounds that bind to and stimulate PURINERGIC P2Y RECEPTORS. Included under this heading are agonists for specific P2Y receptor subtypes.
Compounds that bind to and activate PURINERGIC RECEPTORS.
Drugs that bind to and block the activation of PURINERGIC RECEPTORS.
Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.
Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.
Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.
Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.
Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.
Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.
A class of agents that target at platelet ADP receptor or purinergic receptor P2RY12 with antiplatelet activity.
Compounds that bind to and inhibit the action of 5-LIPOXYGENASE-ACTIVATING PROTEINS.
Compounds that specifically inhibit PHOSPHODIESTERASE 4.
Common variable immune deficiency (CVID) is a disorder that impairs the immune system. People with CVID are highly susceptible to infection from foreign invaders such as bacteria, or more rarely, viruses and often develop recurrent infections, particularly in the lungs, sinuses, and ears. Pneumonia is common in people with CVID. Over time, recurrent infections can lead to chronic lung disease. Affected individuals may also experience infection or inflammation of the gastrointestinal tract, which can cause diarrhea and weight loss. Abnormal accumulation of immune cells causes enlarged lymph nodes (lymphadenopathy) or an enlarged spleen (splenomegaly) in some people with CVID. Immune cells can accumulate in other organs, forming small lumps called granulomas.Approximately 25 percent of people with CVID have an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's tissues and organs. The blood cells are most frequently affected by autoimmune attacks in CVID; the most commonly occurring autoimmune disorders are immune thrombocytopenia, which is an abnormal bleeding disorder caused by a decrease in cell fragments involved in blood clotting called platelets, and autoimmune hemolytic anemia, which results in premature destruction of red blood cells. Other autoimmune disorders such as rheumatoid arthritis can occur. Individuals with CVID also have a greater than normal risk of developing certain types of cancer, including a cancer of immune system cells called non-Hodgkin lymphoma and less frequently, stomach (gastric) cancer.People with CVID may start experiencing signs and symptoms of the disorder anytime between childhood and adulthood; most people with CVID are diagnosed in their twenties or thirties. The life expectancy of individuals with CVID varies depending on the severity and frequency of illnesses they experience. Most people with CVID live into adulthood.There are many different types of CVID that are distinguished by genetic cause. People with the same type of CVID may have varying signs and symptoms.
A condition of decreased or absent presence or activity of signal transducer and activator of transcription 3 protein. Deficiency of this protein is associated with hyper-IgE syndrome.
A rare sex chromosome abnormality in which a male child has an extra X and Y chromosome.
Waldenstrom macroglobulinemia in a patient who has at least one first degree relative with either Waldenstrom macroglobulinemia or another B-cell lymphoproliferative disorder.
Stenosis of the cerebral aqueduct (also known as the mesencephalic duct, aqueductus mesencephali, or aqueduct of Sylvius), which connects the third cerebral ventricle in the diencephalon to the fourth ventricle, which is between the pons and cerebellum.
Any substance that inhibits steroid 5-alpha-reductase, an enzyme that converts testosterone into dihydrotestosterone (DHT). Since DHT has three times greater affinity for androgen receptors than testosterone, inhibition of 5-alpha-reductase results in a strong reduction in the androgenic effects of testosterone.
Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS.
Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.
Cytochrome P450 oxidoreductase deficiency (PORD) is a disorder of steroidogenesis with a broad phenotypic spectrum including cortisol deficiency, altered sex steroid synthesis, disorders of sex development (DSD), and skeletal malformations of the Antley-Bixler syndrome (ABS) phenotype. Cortisol deficiency is usually partial, with some baseline cortisol production but failure to mount an adequate cortisol response in stress. Mild mineralocorticoid excess can be present and causes arterial hypertension, usually presenting in young adulthood. Manifestations of altered sex steroid synthesis include ambiguous genitalia/DSD in both males and females, large ovarian cysts in females, poor masculinization and delayed puberty in males, and maternal virilization during pregnancy with an affected fetus. Skeletal malformations can manifest as craniosynostosis, mid-face retrusion with proptosis and choanal stenosis or atresia, low-set dysplastic ears with stenotic external auditory canals, hydrocephalus, radiohumeral synostosis, neonatal fractures, congenital bowing of the long bones, joint contractures, arachnodactyly, and clubfeet; other anomalies observed include urinary tract anomalies (renal pelvic dilatation, vesicoureteral reflux). Cognitive impairment is of minor concern and likely associated with the severity of malformations; studies of developmental outcomes are lacking.
Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.
Compounds that bind to and activate ADRENERGIC BETA-1 RECEPTORS.
Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.
Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.
Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.
Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.
Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism.
Compounds that bind to and inhibit the activation of ANDROGEN RECEPTORS.
The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. Cervantes-Barragan et al. (2011) proposed a classification of FFDD in which there are 4 subtypes. FFDD1 (Brauer syndrome) is characterized by temporal skin depressions that resemble 'forceps marks.' Other facial anomalies, comprising sparse lateral eyebrows, distichiasis, and a flattened nasal tip, are usually mild. Inheritance is autosomal dominant. FFFD2 (Brauer-Setleis syndrome; 614973) is characterized by bitemporal skin lesions with variable facial findings, including thin and puckered periorbital skin, distichiasis and/or absent eyelashes, upslanting palpebral fissures, a flat nasal bridge with a broad nasal tip, large lips, and redundant facial skin. Inheritance is autosomal dominant. FFDD3 (Setleis syndrome; 227260) is characterized by the same facial features as FFDD2, but the inheritance is autosomal recessive. FFDD4 (614974) is characterized by isolated, preauricular skin lesions with autosomal dominant or recessive inheritance (summary by Slavotinek et al., 2013). Genetic Heterogeneity of Focal Facial Dermal Dysplasia FFDD3 (227260) is caused by mutation in the TWIST2 gene (607556) on chromosome 2q37. FFDD4 (614974) is caused by mutation in the CYP26C1 gene on chromosome 10q23.
Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.
A chromosomal abnormality characterized by the presence of three copies of genetic material for chromosome 13, instead of the normal two. It leads to a variety of abnormalities that include mental retardation, microcephaly, low-set ears, eye structural defects, polydactyly, and limb abnormalities.
Acatalasemia is a condition characterized by very low levels of an enzyme called catalase. Many people with acatalasemia never have any health problems related to the condition and are diagnosed because they have affected family members.Some of the first reported individuals with acatalasemia developed open sores (ulcers) inside the mouth that led to the death of soft tissue (gangrene). When mouth ulcers and gangrene occur with acatalasemia, the condition is known as Takahara disease. These complications are rarely seen in more recent cases of acatalasemia, probably because of improvements in oral hygiene.Studies suggest that people with acatalasemia have an increased risk of developing type 2 diabetes, which is the most common form of diabetes. A higher percentage of people with acatalasemia have type 2 diabetes than in the general population, and the disease tends to develop at an earlier age (in a person's thirties or forties, on average). Researchers speculate that acatalasemia could also be a risk factor for other common, complex diseases; however, only a small number of cases have been studied.
21-hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), a family of autosomal recessive disorders involving impaired synthesis of cortisol from cholesterol by the adrenal cortex. In 21-OHD CAH, excessive adrenal androgen biosynthesis results in virilization in all individuals and salt wasting in some individuals. A classic form with severe enzyme deficiency and prenatal onset of virilization is distinguished from a non-classic form with mild enzyme deficiency and postnatal onset. The classic form is further divided into the simple virilizing form (~25% of affected individuals) and the salt-wasting form, in which aldosterone production is inadequate (=75% of individuals). Newborns with salt-wasting 21-OHD CAH are at risk for life-threatening salt-wasting crises. Individuals with the non-classic form of 21-OHD CAH present postnatally with signs of hyperandrogenism; females with the non-classic form are not virilized at birth.
Syndrome that is characterised by intellectual deficit, deafness, ocular anomalies, T-cell leukaemia, cryptorchidism, hypospadias and spasticity. Mutations in DNA polymerase alpha, leading to increased chromosome breakage, may be responsible for the syndrome. X-linked recessive transmission has been proposed.
A novel synthetic epothilone with potential antineoplastic activity. Epothilone ZK-219477 binds to microtubules, predominantly in tumor cells, thereby inducing microtubule bundling, formation of multipolar spindles, and mitotic arrest in a manner similar to taxanes. Epothilones are poor substrates for the multidrug resistance 1 (MDR1) P-glycoprotein drug efflux pump and, unlike the taxanes, appear to be able to evade some drug-resistance mechanisms. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=473738&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=473738&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61072"" NCI Thesaurus)
X-linked Opitz G/BBB syndrome (X-OS) is a multiple-congenital-anomaly disorder characterized by facial anomalies (hypertelorism, prominent forehead, widow's peak, broad nasal bridge, anteverted nares), genitourinary abnormalities (hypospadias, cryptorchidism, and hypoplastic/bifid scrotum), and laryngotracheoesophageal defects. Developmental delay and intellectual disability are observed in about 50% of affected males. Cleft lip and/or palate are present in approximately 50% of affected individuals. Other malformations (present in <50% of individuals) include congenital heart defects, imperforate or ectopic anus, and midline brain defects (Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis). Wide clinical variability occurs even among members of the same family. Female heterozygotes usually manifest hypertelorism only.
Isolated complex I deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders (McFarland et al., 2004; Kirby et al., 2004). It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome (see 256000), Leber hereditary optic neuropathy (535000), and some forms of Parkinson disease (see 556500) (Loeffen et al., 2000; Pitkanen et al., 1996; Robinson, 1998). Genetic Heterogeneity of Complex I Deficiency Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype-phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible (summary by Haack et al., 2012). However, the majority of cases are caused by mutations in nuclear-encoded genes (Loeffen et al., 2000; Triepels et al., 2001). Complex I deficiency resulting from mutation in nuclear-encoded genes include MC1DN1, caused by mutation in the NDUFS4 gene (602694); MC1DN2 (618222), caused by mutation in the NDUFS8 gene (602141); MC1DN3 (618224), caused by mutation in the NDUFS7 gene (601825); MC1DN4 (618225), caused by mutation in the NDUFV1 gene (161015); MC1DN5 (618226), caused by mutation in the NDUFS1 gene (157655); MC1DN6 (618228), caused by mutation in the NDUFS2 gene (602985); MC1DN7 (618229), caused by mutation in the NDUFV2 gene (600532); MC1DN8 (618230), caused by mutation in the NDUFS3 gene (603846); MC1DN9 (618232), caused by mutation in the NDUFS6 gene (603848); MC1DN10 (618233), caused by mutation in the NDUFAF2 gene (609653); MC1DN11 (618234), caused by mutation in the NDUFAF1 gene (606934); MC1DN12 (301020), caused by mutation in the NDUFA1 gene (300078); MC1DN13 (618235), caused by mutation in the NDUFA2 gene (602137); MC1DN14 (618236), caused by mutation in the NDUFA11 gene (612638); MC1DN15 (618237), caused by mutation in the NDUFAF4 gene (611776); MC1DN16 (618238), caused by mutation in the NDUFAF5 gene (612360); MC1DN17 (618239), caused by mutation in the NDUFAF6 gene (612392); MC1DN18 (618240), caused by mutation in the NDUFAF3 gene (612911); MC1DN19 (618241), caused by mutation in the FOXRED1 gene (613622); MC1DN20 (611126), caused by mutation in the ACAD9 gene (611103); MC1DN21 (618242), caused by mutation in the NUBPL gene (613621); MC1DN22 (618243), caused by mutation in the NDUFA10 gene (603835); MC1DN23 (618244), caused by mutation in the NDUFA12 gene (614530); MC1DN24 (618245), caused by mutation in the NDUFB9 gene (601445); MC1DN25 (618246), caused by mutation in the NDUFB3 gene (603839); MC1DN26 (618247), caused by mutation in the NDUFA9 gene (603834); MC1DN27 (618248), caused by mutation in the MTFMT gene (611766); MC1DN28 (618249), caused by mutation in the NDUFA13 gene (609435); MC1DN29 (618250), caused by mutation in the TMEM126B gene (615533); MC1DN30 (301021), caused by mutation in the NDUFB11 gene (300403); MC1DN31 (618251), caused by mutation in the TIMMDC1 gene (615534); MC1DN32 (618252), caused by mutation in the NDUFB8 gene (602140); and MC1DN33 (618253), caused by mutation in the NDUFA6 gene (602138). Complex I deficiency with mitochondrial inheritance has been associated with mutation in 6 mitochondrial-encoded components of complex I: MTND1 (516000), MTND2 (516001), MTND3 (516002), MTND4 (516003), MTND5 (516005), MTND6 (516006). Most of these patients have a phenotype of Leber hereditary optic neuropathy (LHON; 535000) or Leigh syndrome. Features of complex I deficiency may also be caused by mutation in other mitochondrial genes, including MTTS2 (590085).
A syndrome of gingival fibromatosis, pigmentation disorders, microphthalmia, and delayed psychomotor development. It was first observed in the Kramer family, hence the synonym Kramer syndrome.
A vascular malformation resulting from a developmental error of venous tissue composed of dysmorphic channels lined by flattened endothelium and exhibiting slow turnover. A venous malformation may present as a blue patch on the skin ranging to a soft blue mass. Venous malformations are easily compressible and usually swell in thewhen venous pressure increases (e.g., when held in a dependent position or when a child cries). They may be relatively localized or quite extensive within an anatomic region.
Disorder characterized by severe limitation or total lack of peripheral vision.
A rare cutaneous lesion presenting as a scaly verrucous plaque. Morphologically, the plaque contains nests of basaloid cells.
A neoplasm that arises from glial cells in the spinal cord. Representative examples include astrocytoma, oligodendroglioma, and ependymoma.
Decreased response to thyroid hormones in peripheral tissues and in the pituitary gland.
Abnormality in the process of ejection of semen (usually carrying sperm) from the male reproductive tract.
Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.
Aphthous ulcers of the mouth that are recurrent.
Increase in constituent cells in the PROSTATE, leading to enlargement of the organ (hypertrophy) and adverse impact on the lower urinary tract function. This can be caused by increased rate of cell proliferation, reduced rate of cell death, or both.
An elevated concentration of urobilinogen in the urine. []
An increased response to stimulation that is mediated by amplification of signaling in the CENTRAL NERVOUS SYSTEM (CNS).
A brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter.
A hyperdynamic process resulting from excessive vasodilatation. Impaired blood flow causes inadequate tissue perfusion, which can lead to end-organ damage
A benign condition characterized by the presence of peritoneal implants composed of mature glial tissue. It is usually accompanied by an ovarian teratoma.
A syndrome, usually presenting after midline posterior fossa tumor resection, which is characterized by abnormalities of speech, behavioral or affective disturbances, and diffuse cerebellar dysfunction.
A self-limiting cutaneous vasculitis that typically presents as a clinical triad of purpura, edema, and fever in children between the ages of four months and two years old. It is usually associated with a recent history of upper respiratory infection and/or antibiotic therapy.
Meconium ileus refers to intestinal obstruction due to inspissated meconium in the distal ileum and cecum, which develops in utero and presents shortly after birth as a failure to pass meconium (summary by Romi et al., 2012). Meconium ileus is a known clinical manifestation of cystic fibrosis (CF; 219700), and meconium ileus in the absence of CF is a rare phenomenon (summary by Tal et al., 1985).
A change in disposition or state of mind.
Tremulousness (trembling) of the lens of the eye.
A malignant tumor that has spread from its original (primary) site of growth to another site close to or distant from the primary site.
A tumor that has spread from its original (primary) site of growth to another site, close to or distant from the primary site. Metastasis is characteristic of advanced malignancies, but in rare instances can be seen in neoplasms lacking malignant morphology.
Failure of proper functioning of the right ventricle, with venous engorgement, hepatic enlargement, and subcutaneous edema.
Proliferation of myeloid cells originating from a primitive stem cell.
A plasma cell neoplasm characterized by the deposition of immunoglobulin in tissues, resulting in impaired organ function. It includes the following entities: primary amyloidosis, heavy chain deposition disease, and light chain deposition disease.
A disease-producing enzyme deficiency subject to many variants, some of which cause a deficiency of GLUCOSE-6-PHOSPHATE DEHYDROGENASE activity in erythrocytes, leading to hemolytic anemia.
A nutritional supplement containing the biologically active form of the B9 vitamin folate, 5-methyltetrahydrofolate (L-methylfolate), with potential antineoplastic activity. Upon administration, L-methylfolate is able to provide methyl groups allowing an increase in the level of DNA methylation in the promoter regions of certain tumor-promoting genes, thereby reversing the DNA hypomethylation of these genes and inactivating them. This may result in a decrease of both tumor cell proliferation and tumor progression. In addition, administration of L-methylfolate may sensitize tumor cells to the cytotoxic effects of other chemotherapeutic agents. Unlike folic acid, L-methylfolate is able to cross the blood brain barrier and could be beneficial in the treatment of brain tumors. DNA hypomethylation of certain genes leads to chromosome instability and contributes to tumor development.
A rare, autosomal recessive inherited disorder usually caused by mutations in the THRB gene. It is characterized by a defective physiological resistance to thyroid hormones, resulting in the elevation of thyroxin and triiodothyronine in the serum.
A malignant neoplasm of the liver developed in childhood. Representative examples include hepatoblastoma, undifferentiated (embryonal) sarcoma, and extrarenal rhabdoid tumor.
An intravenous colloidal solution containing trivalent iron (Fe3+) chelated to isomaltosides, used as iron replacement. The iron in iron isomaltoside 1000 is strongly bound to the carbohydrate particles; each particle contains a trivalent iron core and a carbohydrate shell of isomaltosides which protects and stabilizes the iron core. This results in low levels of free iron and decreases inorganic, unbound iron-related toxicities thereby allowing for administration of higher doses of iron as compared to other iron-containing formulations. Upon parenteral administration and degradation of the carbohydrate shell, the iron in iron isomaltoside 1000 is released and replenishes iron stores.
An herbal remedy derived from the dried root of Dioscorea villosa, a perennial vine native to North America, Mexico and Asia. The root contains indigenous plant phytosterol estrogens such as diosgenin, which espouse therapeutic effects on female hormonal regulation and alleviate the symptoms of menopause, as well as induce antiproliferative pro-apoptotic effects in a diverse range of tumor cells.
The thin, sharp part of a knife, tool, or weapon designed to cut things.
A radioimmunoconjugate consisting of the murine IgG1 kappa monoclonal antibody capromab (7E11-C5.3), conjugated to the linker-chelator glycyl-tyrosyl-(N,-diethylenetriaminepentaacetic acid)-lysine hydrochloride (GYK-DTPA-HCl) and labeled with radioisotope indium In 111, with ligand-binding and gamma-emitting activities. Upon intravenous administration, indium In 111-capromab pendetide binds to a cytoplasmic epitope of human prostate specific membrane antigen (PSMA) expressed on prostate tumor cell surfaces via its capromab moiety and, upon internalization, allows radioimmunolocalization with gamma scintigraphy. PSMA is a cell surface glycoprotein abundantly expressed by prostate epithelium and is typically overexpressed by prostate cancer cells.
Abnormality of the spatial relationship of the atria to other components of the heart.
A benign lesion that usually affects the proximal small bones of the hands or feet. Grossly it consists of a cartilage cap and a bony stalk. Microscopically it is characterized by the presence of spindle cells, cartilage, and bone, usually in a disorganized pattern compared to subungual exostosis. Enlarged (bizarre) chondrocytes are present in the cartilage. Swelling with or without pain is present. Recurrences following resection have been reported in approximately half of cases.
Deposition of calcium salts in muscle tissue.
A benzofuran, indole, and piperazine derivative that functions as a SEROTONIN UPTAKE INHIBITOR and partial SEROTONIN 5-HT1 RECEPTOR AGONIST. It is used as an ANTIDEPRESSIVE AGENT.
A formulation containing the hydrochloride salt form of diphenoxylate, a synthetic opioid of the phenylpiperidine class, and the sulfate salt form of the anticholinergic agent atropine, with antidiarrheal activity. Upon oral administration, diphenoxylate acts on opioid receptors in the gastrointestinal (GI) tract, thereby decreasing GI motility, prolonging transit time, and preventing diarrhea. Through its anticholinergic effects, atropine prevents deliberate over-usage of diphenoxylate by triggering very unpleasant side effects (SEs), such as severe weakness and nausea.
An antibody-drug conjugate (ADC) directed against the tumor necrosis factor (TNF) receptor CD30 with potential antineoplastic activity. Brentuximab vedotin is generated by conjugating the chimeric anti-CD30 monoclonal antibody SGN-30 to the cytotoxic agent monomethyl auristatin E (MMAE) via a valine-citrulline peptide linker. Upon administration and internalization by CD30-positive tumor cells, brentuximab vedotin undergoes enzymatic cleavage, releasing MMAE into the cytosol; MMAE binds to tubulin and inhibits tubulin polymerization, which may result in G2/M phase arrest and tumor cell apoptosis. Transiently activated during lymphocyte activation, CD30 (tumor necrosis factor receptor superfamily, member 8;TNFRSF8) may be constitutively expressed in hematologic malignancies including Hodgkin lymphoma and some T-cell non-Hodgkin lymphomas. The linkage system in brentuximab vedotin is highly stable in plasma, resulting in cytotoxic specificity for CD30-positive cells.
A locked nucleic acid (LNA) antisense oligonucleotide targeting survivin mRNA, with potential antineoplastic activity. EZN-3042 hybridizes to survivin mRNA, thereby blocking translation of survivin protein and inhibiting survivin-induced anti-apoptotic activity and promoting tumor cell apoptosis in survivin-overexpressing tumor cells. Survivin, a member of the inhibitor of apoptosis (IAP) family expressed during embryonic development, is upregulated in a variety of human cancers while absent in most normal adult cells; its expression in tumors is associated with a more aggressive phenotype, decreased survival, and increased resistance to chemotherapy. LNAs contain a methylene bridge linking 2'-oxygen and 4'-carbon of ribose sugar rings, thereby increasing their stability and decreasing degradation.
A small vessel vasculitis affecting the skin and/or internal organs. It is characterized by the presence of neutrophils and fibrinoid necrosis in small arteries and venules. It may be idiopathic or the result of drug treatment, infections, food intake, collagen vascular disorders, inflammatory bowel disease, or cancer.
A synthetic, glycomimetic molecule and pan-selectin antagonist, with potential use in a vaso-occlusive crisis. Upon administration, GMI-1070 prevents the interaction between leukocytes and the endothelium and may prevent cell activation and adhesion. By preventing selectin-mediated cell adhesion in sickle cell anemia, this agent may inhibit red blood cell-white blood cell interactions, normalize blood flow and reduce inflammation and vascular occlusive pain. GMI-1070 has the strongest antagonistic activity towards E-selectin but a sulfate-binding domain allows for interactions with P- and L-selectins. Selectins, containing lectin- and EGF-like domains, are a family of cell adhesion molecules implicated in inflammatory processes and cancer.
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position. [HPO:probinson]
An orally bioavailable small molecule with potential antineoplastic activity. Foretinib binds to and selectively inhibits hepatocyte growth factor (HGF) receptor c-MET and vascular endothelial growth factor receptor 2 (VEGFR2), which may result in the inhibition of tumor angiogenesis, tumor cell proliferation and metastasis. The proto-oncogene c-MET has been found to be over-expressed in a variety of cancers. VEGFR2 is found on endothelial and hematopoietic cells and mediates the development of the vasculature and hematopoietic cells through VEGF signaling.
A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER.
A C-glucoside with a thiophene ring that is an orally available inhibitor of sodium-glucose transporter 2 (SGLT2) with antihyperglycemic activity. Canagliflozin is also able to reduce body weight and has a low risk for hypoglycemia.
A benzophenone derivative and water soluble valine prodrug of the tubulin binding agent S516, with potential tubulin-inhibiting, vascular-disrupting and antineoplastic activity. Upon administration, tubulin polymerization inhibitor CKD-516 is converted into its active metabolite S-516 that binds to tubulin and prevents its polymerization in tumor blood vessel endothelial cells and tumor cells. This blocks the formation of the mitotic spindle and leads to cell cycle arrest at the G2/M phase. As a result, this agent disrupts the tumor vasculature and tumor blood flow, deprives tumor cells of nutrients and induces tumor cell apoptosis. In addition, this agent has a direct cytotoxic effect on tumor cells by inhibiting tubulin polymerization.
A disulfonyl derivative of phenyl-tert-butyl nitrone (PBN), with potential anti-glioma activity. Although the exact mechanism(s) of action of OKN007 are still largely unknown, this agent appears to inhibit cancer cell proliferation and migration. This agent appears to inhibit the activity of sulfatase 2 (SULF2), a highly specific endoglucosamine-6-sulfatase that is overexpressed in the extracellular matrix of cancer cells and catalyzes the removal of sulfate from the 6-O-sulfate esters of heparin. In addition, OKN007 may induce changes in tumor metabolism and scavenge free radicals.
A synthetic, orally bioavailable, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Onalespib selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability and degradation of many oncogenic signaling proteins.
An orally active, synthetic small molecule and an antagonist of a subset of the B-cell leukemia 2 (Bcl-2) family of proteins with potential antineoplastic activity. Navitoclax selectively binds to apoptosis suppressor proteins Bcl-2, Bcl-XL, and Bcl-w, which are frequently overexpressed in a wide variety of cancers, including those of the lymph, breast, lung, prostate, and colon, and are linked to tumor drug resistance. Inhibition of these apoptosis suppressors prevents their binding to the apoptotic effectors Bax and Bak proteins, thereby triggering apoptotic processes in cells overexpressing Bcl-2, Bcl-XL, and Bcl-w. This eventually reduces tumor cell proliferation.
An orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Edoxaban is administered as edoxaban tosylate. This agent has an elimination half-life of 9-11 hours and undergoes renal excretion.
A uridine monophosphate analog inhibitor of HEPATITIS C VIRUS (HCV) polymerase NS5B that is used as an ANTIVIRAL AGENT in the treatment of CHRONIC HEPATITIS C.
A fully recombinant form of the human pentraxin 2 (PTX2) protein with potential antifibrotic activity. Upon intravenous administration, recombinant human serum amyloid P/pentraxin 2 (PRM-151) may inhibit myofibroblast generation by preventing the differentiation of circulating monocytes into fibrocytes and profibrotic macrophages. PTX2 is a circulating plasma protein that belongs to the class of pattern recognition receptors (PRR) of the innate immune system.
A pregnancy involving two fetuses that share the same chorion but have separate amniotic sacs.
A pregnancy involving two fetuses that each have separate chorions and amniotic sacs.
A mixture of neutral lipids (70%), phosphatidylcholine (20%) and phosphatidylethanolamine (10%) extracted from egg yolk. AL721 removes cholesterol from outer cell membranes, increases membrane fluidity, and impairs virus attachment to cell receptors. AL721 has been studied for diseases and conditions where altered membrane fluidity plays a role.
A fetal position during delivery in which the head of the fetus descends into the maternal pelvis.
A nuclease-stabilized synthetic ribozyme (ribonucleic acid enzyme) with potential anti-angiogenesis activity. Ribozyme RPI.4610 specifically recognizes the mRNA for FLT1 (vascular endothelial growth factor receptor 1; VEGFR1), and hydrolyzes the mRNA, thereby preventing VEGFR1 proteins from being made. This may prevent VEGF-stimulated angiogenesis in cancerous tissue and metastasis.
Stage IIIC includes: Any T, N3, M0. N3: Metastases in ipsilateral infraclavicular (level III) axillary lymph nodes(s) with or without level I, II axillary lymph node involvement; or in clinically detected ipsilateral internal mammary lymph node(s) with clinically evident level I, II axillary lymph node metastases; or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 7th Ed.)
A fully human monoclonal antibody directed against the B-cell surface antigen CD40 with potential antineoplastic activity. Lucatumumab binds to and inhibits CD40, thereby inhibiting CD40 ligand-induced cell proliferation and triggering cell lysis via antibody-dependent cellular cytotoxicity (ADCC) in cells overexpressing CD40. CD40, an integral membrane protein found on the surface of B lymphocytes, is a member of the tumor necrosis factor receptor superfamily and is highly expressed in a number of B-cell malignancies.
A small-molecule proapoptotic agent with potential antineoplastic activity. Sepantronium bromide selectively inhibits survivin expression in tumor cells, resulting in inhibition of survivin antiapoptotic activity (via the extrinsic or intrinsic apoptotic pathways) and tumor cell apoptosis. Survivin, a member of the inhibitor of apoptosis (IAP) gene family, is expressed during embryonal development and is absent in most normal, terminally differentiated tissues; upregulated in a variety of human cancers, its expression in tumors is associated with a more aggressive phenotype, shorter survival times, and a decreased response to chemotherapy.
An orally active second generation tetrathiomolybdate analog with anti-angiogenic and antineoplastic activities. ATN-224 selectively chelates the copper ion in superoxide dismutase 1 (SOD1) in endothelial cells, thereby depleting SOD1 of copper and inhibiting its activity. Inhibition of SOD1 interferes with the activation of several signal transduction pathways required for cellular proliferation and angiogenesis, including those mediated by ERK1/2 and FAK and Src kinases. This results in an inhibition of cell proliferation and angiogenesis as well as induction of apoptosis.
The hydrochloride salt form of verubulin, a quinazoline derivative with potential dual antineoplastic activities. Verubulin binds to and inhibits tubulin polymerization and interrupts microtubule formation, resulting in disruption of mitotic spindle assembly, cell cycle arrest in the G2/M phase, and cell death. This agent is not a substrate for several subtypes of multidrug resistance ABC transporters, such as P-glycoprotein, multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein 1 (BCRP1); therefore, it may be useful for treating multidrug resistant (MDR) tumors that express these transporters. In addition, as a vascular disrupting agent (VDA), verubulin appears to disrupt tumor microvasculature specifically, which may result in acute ischemia and massive tumor cell death.
A second-generation antisense oligonucleotide against survivin mRNA with potential antitumor activity. Oligonucleotide LY2181308 hybridizes to survivin mRNA, thereby blocking translation of survivin protein, a member of the inhibitor of apoptosis (IAP) family. Survivin, expressed during embryonal development, is upregulated in a variety of human cancers while absent in most normal adult cells; its expression in tumors is associated with a more aggressive phenotype, shorter survival times, and a decreased response to chemotherapy. Silencing expression of survivin potentially leads to restoration of the apoptotic process in cancer cells, thereby facilitating chemotherapeutic treatments.
An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) 1 and 2. MEK 1 and 2 are dual specificity kinases that are essential mediators in the activation of the RAS/RAF/MEK/ERK pathway, are often upregulated in various cancer cells, and are drivers of diverse cellular responses, including proliferation. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.
A recombinant, fully human monoclonal antibody directed against the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Ganitumab binds to membrane-bound IGF-1R, preventing binding of the ligand IGF-1 and the subsequent triggering of the PI3K/Akt signaling pathway; inhibition of this survival signaling pathway may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. IGF-1R is a tyrosine kinase and a member of the insulin receptor family. IGF-1R activation stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been highly implicated in tumorigenesis and metastasis.
An orally available small molecule with potential antineoplastic activity. Quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs), resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. Mutations in FLT3, resulting in constitutive activation, are the most frequent genetic alterations in acute myeloid leukemia (AML) and occur in approximately one-third of AML cases.
An orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling.
A type of dental dysplasia occurring in dentinogenesis imperfecta in which the pulp chambers are enlarged and there is a reduced amount of coronal dentin.
Tissue degeneration and diminished size of the thyroid gland.
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate). [HPO:probinson]
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
The hydrochloride salt form of an orally bioavailable multitargeted receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities. Ponatinib inhibits unmutated and all mutated forms of Bcr-Abl, including T315I, the highly drug therapy-resistant missense mutation of Bcr-Abl. This agent also inhibits other tyrosine kinases including those associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs); in addition, it inhibits the tyrosine kinase receptor TIE2 and FMS-related tyrosine kinase receptor-3 (Flt3). RTK inhibition by ponatinib may result in the inhibition of cellular proliferation and angiogenesis and may induce cell death. Bcr-Abl is a fusion tyrosine kinase encoded by the Philadelphia chromosome.
An oral capsule formulation of a traditional Chinese herbal medicine with potential analgesic activity. In addition to other herbs, seeds and fruits, blue citrus-based herbal capsule contains the Chinese herb blue citrus (qing pi), which is produced from the dried immature green peel of the tangerine Citrus reticulata Blanco. Blue citrus contains large amounts of limonene, citral and synephrine, which may attribute to its analgesic activity. However, due to the complexity of its chemical components, the exact mechanism of action of this agent remains to be determined.
Stage I includes: (T1, N0, M0). T1: Tumor invades subepithelial connective tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage II includes: (T1, N1, M0); (T2, N0, M0); (T2, N1, M0). T1: Tumor invades subepithelial connective tissue. N0: No regional lymph node metastasis. N1: Metastasis in a single superficial, inguinal lymph node. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage III includes: (T1, N2, M0); (T2, N2, M0); (T3, N0, M0); (T3, N1, M0); (T3, N2, M0). T1: Tumor invades subepithelial connective tissue. T2: Tumor invades corpus spongiosum or cavernosum. T3: Tumor invades urethra or prostate. N0: No regional lymph node metastasis. N1: Metastasis in single superficial, inguinal lymph node. N2: Metastasis in multiple or bilateral superficial inguinal lymph nodes. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Colorectal cancer which directly invades other organs or structures.
Colorectal cancer which penetrates the visceral peritoneum.
A preparation of autologous peripheral blood T-lymphocytes (PBTL) that have been genetically modified to express the chimeric antigen receptor (CAR) anti-CD19/CD3 zeta chain fusion protein coupled to the intracellular signal domain of CD28 antigen, with potential immunostimulating and antineoplastic activities. Upon administration, autologous PBTL CD19CAR-28 zeta may stimulate host cytotoxic T lymphocyte (CTL) and antibody responses against CD19-expressing tumor cells, resulting in tumor cell lysis. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. CD3 zeta is one of several membrane-bound polypeptides found in the T-cell receptor (TCR)/CD3 complex and regulates the assembly of complete TCR complexes and their expression on the cell surface. CD28 is essential for CD4+ T-cell proliferation, interleukin-2 production, and T-helper type-2 (Th2) development.
Autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTL) that have been genetically modified to express a T-cell chimeric antigen receptor (CAR) targeting the CD19 antigen, with potential immunotherapeutic activity. The CAR consists of a single chain Fv of anti-CD19 IgG1 coupled with an intracellular signaling region of the zeta-chain of the TCR/CD3 complex (CD3 zeta). Autologous EBV-CTL CD19CAR zeta directs the T-lymphocytes to CD19-expressing tumor cells, stimulating a selective toxicity to tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.
A finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v6 classification system.
Prostate cancer extending beyond the capsule of the prostate gland, without involvement of the seminal vesicles. (from AJCC 6th Ed.)
Prostate cancer extending beyond the capsule of the prostate gland, with involvement of the bladder and/or rectum. (from AJCC 6th Ed.)
A finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v6 classification system.
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v6 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
Cutaneous melanoma in which the primary tumor cannot be assessed. (from AJCC 6th Ed.)
Cutaneous melanoma 1.0mm or less in thickness, with or without ulceration. (from AJCC 6th Ed.)
Cutaneous melanoma 1.0mm or less in thickness and Clark level II or III, with no ulceration. (from AJCC 6th Ed.)
Cutaneous melanoma 1.0mm or less in thickness, with ulceration and/or Clark level IV or V. (from AJCC 6th Ed.)
Cutaneous melanoma in which the regional lymph nodes cannot be assessed. (from AJCC 6th Ed.)
Cutaneous melanoma with involvement of one lymph node. (from AJCC 6th Ed.)
Cutaneous melanoma with microscopic, clinically occult metastasis to a single lymph node. (from AJCC 6th Ed.)
Cutaneous melanoma with macroscopic, clinically apparent metastasis to a single lymph node. (from AJCC 6th Ed.)
Cutaneous melanoma involving two to three regional lymph nodes, or involving the regional intra-lymphatic system without nodal involvement. (from AJCC 6th Ed.)
Cutaneous melanoma with microscopic, clinically occult metastasis to two or three regional lymph nodes. (from AJCC 6th Ed.)
Cutaneous melanoma with macroscopic, clinically apparent metastasis to two or three regional lymph nodes. (from AJCC 6th Ed.)
Cutaneous melanoma without involvement of regional lymph nodes, with satellite or in-transit metastasis. (from AJCC 6th Ed.)
Cutaneous melanoma with distant metastasis. (from AJCC 6th Ed.)
Cutaneous melanoma with metastasis to skin, subcutaneous tissues or distant lymph nodes. (from AJCC 6th Ed.)
Cutaneous melanoma with metastasis to lung. (from AJCC 6th Ed.)
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes. TNM pathologic regional lymph nodes findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes. TNM pathologic regional lymph nodes findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v6 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A clinical finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v6 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, endoscopy, biopsy or laboratory testing.
Stage II includes IIA (T3, N0, M0) and IIB (T4, N0, M0). T3: Tumor invades through the muscularis propria into the subserosa, or into nonperitonealized pericolic or perirectal tissues. T4: Tumor directly invades other organs or structures, and/or perforates the visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.)
A fully human monoclonal antibody directed against nerve growth factor (NGF) with potential analgesic activity. Upon administration, fulranumab binds to NGF, preventing its binding to and activation of the NGF receptors TrkA and p75NTR. Inhibition of the NGF pathway may prevent the perception of pain and may induce analgesia. NGF, a neurotrophic factor that plays a key role in neuropathic and inflammatory-induced pain, promotes hyperalgesia and allodynia.
A water-soluble, positively charged fusion protein consisting of a luteinizing hormone releasing hormone (LHRH) receptor-targeting ligand conjugated to the membrane-disrupting peptide CLIP 71 with membrane-disrupting and potential antineoplastic activities. The LHRH ligand moiety of membrane-disrupting peptide EP-100 specifically binds to LHRH receptors, which are upregulated on a variety of human cancer cell types. Subsequently, the positively charged CLIP 71 moiety of this agent interacts with the negatively charged membrane on the cancer cell surface, which may result in cell membrane disruption and cell lysis.
A tablet preparation formulated for vaginal administration containing a micronized synthetic form of the endogenous steroid hormone progesterone with progesterone activity. Upon vaginal insertion, progesterone binds to the progesterone receptor, resulting in dissociation of heat shock proteins, receptor phosphorylation, and transcription activation through direct or indirect interaction with transcription factors. This agent exerts inhibitory effects on estrogen by decreasing the number of estrogen receptors and increasing its metabolism to inactive metabolites. Progesterone induces secretory changes in the endometrium, decreases uterine contractility during pregnancy, and maintains pregnancy.
Stage III includes: IIIA (T1-T2, N1, M0); IIIB (T3-T4, N1, M0); IIIC (Any T, N2, M0). N1: Metastasis in 1 to 3 regional lymph nodes. N2: Metastasis in 4 or more regional lymph nodes. M0: No distant metastasis. (AJCC 6th ed.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis. (AJCC 6th ed.)
Prostate cancer in which the status of distant metastasis cannot be assessed. (from AJCC 6th Ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); T4a: Maxillary sinus: Moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. Nasal cavity and ethmoid sinus: Moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Nasal cavity and ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Nasal cavity and ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. T3: Maxillary sinus: Tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. Nasal cavity and ethmoid sinus: Tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: T3, N0, M0. T3: Mucosal disease N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T3-T4a, N1, M0). T4a: Moderately advanced disease. Tumor involves deep soft tissue, cartilage, bone, or overlying skin. T3: Mucosal disease. N0: No regional lymph node metastases. N1: Tumor with regional lymph node metastases. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: T4b, Any N, M0. T4b: Very advanced disease. Tumor involves brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space, or mediastinal structures. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1a, M0); (T1, N1b, M0); (T2, N1b, M0); (T3, N1b, M0); (T4a, N1b, M0). T4a: Moderately advanced local disease. Tumor of any size extending beyond the thyroid gland capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve. T1: Tumor size 2 cm or less in greatest dimension, limited to the thyroid gland. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid gland. T3: Tumor more than 4 cm in greatest dimension and limited to the thyroid gland, or tumor of any size with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues). N0: No regional lymph node metastasis. N1a: Metastasis to pretracheal, paratracheal or prelaryngeal/Delphian lymph nodes (Level VI lymph nodes). N1b: Metastasis to unilateral, bilateral or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII). M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: T4b, Any N, M0. T4b: Very advanced disease. Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1a, M0); (T1, N1b, M0); (T2, N1b, M0); (T3, N1b, M0); (T4a, N1b, M0). T4a: Moderately advanced local disease. Tumor of any size extending beyond the thyroid gland capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve. T1: Tumor size 2 cm or less in greatest dimension, limited to the thyroid gland. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid gland. T3: Tumor more than 4 cm in greatest dimension and limited to the thyroid gland, or tumor of any size with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues). T4b: Very advanced disease. Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels. N0: No regional lymph node metastasis. N1a: Metastasis to pretracheal, paratracheal or prelaryngeal/Delphian lymph nodes (Level VI lymph nodes). N1b: Metastasis to unilateral, bilateral or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII). M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: T4a, Any N, M0. T4a: Intrathyroidal anaplastic carcinoma. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVB includes: T4b, Any N, M0. T4b: Anaplastic carcinoma with gross extrathyroid extension. M0: No distant metastasis. (AJCC 7th ed.)
A demethoxy derivative of doxorubicin with antineoplastic activity.
A potent, selective and orally bioavailable, cyanopyrrolidine-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity.
A dual peroxisome proliferator-activated receptor (PPAR) alpha and gamma agonist, with hypoglycemic activity.
A long-acting, orally bioavailable, pyrrolidine-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Teneligliptin may also reduce plasma triglyceride levels through a sustained increase in GLP-1 levels.
An insulin sensitizer with hypoglycemic activity. Tibeglisene is also able to reduce serum triglyceride and cholesterol concentrations.
An isoquinoline with activity against myxoviruses and paramyxoviruses.
A hydrochloride salt form of memotine, an isoquinoline with activity against myxoviruses and paramyxoviruses.
An orally available ester prodrug form of sulopenem, a thiopenem with broad-spectrum antibacterial activity against most gram-positive and gram-negative bacteria. After oral administration of sulopenem etzadroxil, the ester bond is cleaved, releasing active sulopenem. Sulopenem is not active against Pseudomonas aeruginosa. In addition, this agent is fairly stable against hydrolysis by various beta-lactamases.
A synthetic, colchicine analogue with potential antineoplastic activity. Mivobulin targets and binds to colchicine-binding site on tubulin, thereby inhibiting microtubule polymerization, the assembly of the mitotic spindle and mitosis. This eventually results in cell cycle arrest, apoptosis and a reduction in cellular proliferation.
A spironolactone derivative and a potent aldosterone antagonist on mineralocorticoid biosynthesis with diuretic activity. As an aldosterone antagonist, oxprenoate may inhibit sodium resorption in the collecting duct and may eventually lead to diuresis.
Stage I includes: IA: (TI, N0, M0) and IB: (T2, N0, M0). TI: Tumor 3 cm or less in greatest dimension surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus. T2: Tumor with any of the following features of size or extent: More than 3cm in greatest dimension. Involves main bronchus, 2cm or more distal to the carina. Invades the visceral pleura. N0: No regional lymph metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage III includes: IIIA (T1, N2, M0); (T2, N2, M0); (T3, N1,M0); (T3, N2, M0) or IIIB (Any T, N3, M0); (T4, Any N, M0). N1: Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes including involvement by direct extension of the primary tumor. N2: Metastasis to ipsilateral mediastinal and/or subcarinal lymph node(s). N3: Metastasis to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s). T1: Tumor is 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, and without bronchoscopic evidence of invasion more proximal than the lobar bronchus. T2: Tumor has any of the following features of size or extent: more than 3 cm in greatest dimension; involves the main bronchus, 2 cm or more distal to the carina; invades the visceral pleura; associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung. T3: Tumor (of any size) directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung. T4: Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina; or separate tumor nodules in the same lobe; or tumor with a malignant pleural effusion. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis present. (AJCC 6th ed.) - 2003
A human monoclonal antibody directed against interleukin-22 (IL-22) with anti-inflammatory activity. Fezakinumab binds to IL-22 and prevents the activity of this interleukin. This leads to an inhibition of inflammation. IL-22, a cytokine and member of the IL-10 superfamily, plays a key role during inflammatory responses.
A humanized monoclonal antibody against interleukin 13 (IL-13) with immunosuppressive and anti-asthmatic activities. Lebrikizumab binds to IL-13 and inhibits IL-13-mediated pathways. IL-13, a cytokine mainly secreted by type 2 helper T cells, plays a key role in the induction of allergic inflammation.
Stage IIA includes: (T3, N0, M0); (T2, N1, M0); (T1, N2, M0). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: (T4a, N0, M0); (T3, N1, M0); (T2, N2, M0); (T1, N3, M0). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates subserosal connective tissue without invasion of visceral peritoneum or adjacent structures. T4a: Tumor invades serosa (visceral peritoneum). N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIC includes: (T4b, N2, M0); (T4b, N3, M0); (T4a, N3, M0). T4a: Tumor invades serosa (visceral peritoneum). T4b: Tumor invades adjacent structures. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IA includes: T1, N0, M0, G1, GX, Tumor location: Any. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IB includes: (T1, N0, M0, G2-3, Tumor location: Any); (T2-3, N0, M0, G1, GX, Tumor location: Lower, X). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IA includes: T1, N0, M0, G1-2, X. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. G2: Moderately differentiated. GX: Grade cannot be assessed-stage grouping as G1. (AJCC 7th ed.)
Stage IB includes: (T1, N0, M0, G3); (T2, N0, M0, G1-2, GX). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. G2: Moderately differentiated. G3: Poorly differentiated. GX: Grade cannot be assessed-stage grouping as G1. (AJCC 7th ed.)
Stage IIIA includes: (T1-2, N2, M0, Any G); (T3, N1, M0, Any G); (T4a, N0, M0, Any G). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T4a: Resectable tumor invading pleura, pericardium, or diaphragm. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: T3, N2, M0, Any G. T3: Tumor invades adventitia. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIC includes: (T4a, N1-2, M0, Any G); (T4b, Any N, M0, Any G); (Any T, N3, M0, Any G). T4a: Resectable tumor invading pleura, pericardium, or diaphragm. T4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: (T1-2, N2, M0, Any G, Tumor location: Any); (T3, N1, M0, Any G, Tumor location: Any); (T4a, N0, M0, Any G, Tumor location: Any). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T4a: Resectable tumor invading pleura, pericardium, or diaphragm. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IIIB includes: T3, N2, M0, Any G, Tumor location: Any. T3: Tumor invades adventitia. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IIIC includes: (T4a, N1-2, M0, Any G, Tumor location: Any); (T4b, Any N, M0, Any G, Tumor location: Any); (Any T, N3, M0, Any G, Tumor location: Any). T4a: Resectable tumor invading pleura, pericardium, or diaphragm. T4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor invades through the muscularis propria into the subserosa or into the nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: T4, N0, M0. T4: Tumor perforates the visceral peritoneum or directly invades other organs or structures (including other loops of small intestine, mesentery, or retroperitoneum more than 2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: Any T, N1, M0. N1: Metastasis in 1-3 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: Any T, N2, M0. N2: Metastasis in four or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
A non-Hodgkin or Hodgkin lymphoma that has metastasized to the central nervous system following the initial presentation in another nodal or extranodal site.
Stage I includes: (T1, N0, M0); (T2, N0, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor invades through the muscularis propria into subserosa or into mesoappendix. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: T4a, N0, M0. T4a: Tumor penetrates visceral peritoneum including mucinous peritoneal tumor within the right lower quadrant. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIC includes: T4b, N0, M0. T4b: Tumor directly invades other organs or structures. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: (T1, N1, M0); (T2, N1, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. N1: Metastasis in 1-3 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: (T3, N1, M0); (T4, N1, M0). T3: Tumor invades through the muscularis propria into subserosa or into mesoappendix. T4: Tumor penetrates visceral peritoneum including mucinous peritoneal tumor within the right lower quadrant and/or directly invades other organs or structures. N1: Metastasis in 1-3 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIC includes: Any T, N2, M0. N2: Metastasis in four or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: Any T, N0, M1a, G1. N0: No regional lymph node metastasis. M1a: Intraperitoneal metastasis beyond the right lower quadrant, including pseudomyxoma peritonei. G1: Well differentiated tumor. (AJCC 7th ed.)
Stage IVB includes: (Any T, N0, M1a, G2, G3); (Any T, N1, M1a, Any G); (Any T, N2, M1a, Any G). N0: No regional lymph node metastasis. N1: Metastasis in 1-3 regional lymph nodes. N2: Metastasis in four or more regional lymph nodes. M1a: Intraperitoneal metastasis beyond the right lower quadrant, including pseudomyxoma peritonei. G2: Moderately differentiated tumor. G3: Poorly differentiated tumor. (AJCC 7th ed.)
Stage IVC includes: Any T, Any N, M1b, Any G. M1b: Nonperitoneal metastasis. (AJCC 7th ed.)
Stage I includes: T1, N0, M0. T1: Tumor 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T2, T3, N0, M0. T2: Tumor more than 2 cm but not more than 4 cm or with extension to the cecum. T3: Tumor more than 4 cm or with extension to the ileum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: (T4, N0, M0); (Any T, N1, M0). T4: Tumor directly invades other adjacent organs or structures, e.g., abdominal wall and skeletal muscle. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIC includes: T4b, N0, M0. T4b: Tumor directly invades or is adherent to other organs or structures. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IVA includes: Any T, Any N, M1a. M1a: Metastasis confined to one organ or site (e.g., liver, lung, ovary, nonregional node). (AJCC 7th ed.)
Stage IVB includes: Any T, Any N, M1b. M1b: Metastases in more than one organ/site or the peritoneum. (AJCC 7th ed.)
Stage IA includes: T1 or T2, N0, M0, Mitotic rate: Low. T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm, but not more than 5 cm, in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IB includes: T3, N0, M0, Mitotic rate: Low. T3: Tumor more than 5 cm, but not more than 10 cm, in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: (T1, N0, M0, Mitotic rate: High); (T2, N0, M0, Mitotic rate: High); (T4, N0, M0, Mitotic rate: Low). T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm, but not more than 5 cm, in greatest dimension. T4: Tumor more than 10 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: T3, N0, M0, Mitotic rate: High. T3: Tumor more than 5 cm, but not more than 10 cm, in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: T4, N0, M0, Mitotic rate: High. T4: Tumor more than 10 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: (Any T, N1, M0, Mitotic rate: Any rate); (Any T, Any N, M1, Mitotic rate: Any rate). N1: Regional lymph node metastasis. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage I includes: T1 or T2, N0, M0, Mitotic rate: Low. T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm, but not more than 5 cm, in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T3, N0, M0, Mitotic rate: Low. T3: Tumor more than 5 cm, but not more than 10 cm, in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: (T1, N0, M0, Mitotic rate: High); (T4, N0, M0, Mitotic rate: Low). T1: Tumor 2 cm or less in greatest dimension. T4: Tumor more than 10 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: (T2, N0, M0, Mitotic rate: High); (T3, N0, M0, Mitotic rate: High); (T4, N0, M0, Mitotic rate: High). T2: Tumor more than 2 cm, but not more than 5 cm, in greatest dimension. T3: Tumor more than 5 cm, but not more than 10 cm, in greatest dimension. T4: Tumor more than 10 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: (Any T, N1, M0, Mitotic rate: Any rate); (Any T, Any N, M1, Mitotic rate: Any rate). N1: Regional lymph node metastasis. M1: Distant metastasis. (AJCC 7th ed.)
The orally bioavailable mesylate salt of the 17-allylaminogeldanamycin (17-AAG) small-molecule inhibitor of several receptor protein tyrosine kinases with potential antiangiogenic and antineoplastic activities. Telatinib binds to and inhibits the vascular endothelial growth factor receptors (VEGFRs) type 2 and 3, platelet-derived growth factor receptor beta (PDGFRb) and c-Kit, which may result in the inhibition of angiogenesis and cellular proliferation in tumors in which these receptors are upregulated. These telatinib-inhibited receptor protein tyrosine kinases are overexpressed or mutated in many tumor cell types and may play key roles in tumor angiogenesis and tumor cell proliferation. 17-AAG is a synthetic analogue of the benzoquinone ansamycin antibiotic geldanamycin and has also been found to inhibit the molecular chaperone Hsp90.
An indication or description that a drug accountability test has occurred.
A character or string that represents a finding of the event or intervention.
An indication or description that a vital signs test has occurred.
Stage 0 includes: Tis, N0, M0. Tis (applies only to stomach): Carcinoma in situ/dysplasia (tumor size less than 0.5 mm), confined to mucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage I includes: T1, N0, M0. T1: Stomach: tumor invades lamina propria or submucosa and is 1 cm or less in size; duodenum /jejunum/ileum: tumor invades lamina propria or submucosa and is 1 cm or less in size; ampulla: tumor 1 cm or less; colon or rectum: tumor invades lamina propria or submucosa and is 2 cm or less. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIA includes: T2, N0, M0. T2: Stomach/ duodenum /jejunum/ileum: tumor invades muscularis propria or is more than 1 cm in size; ampulla: tumor is more than 1 cm in size; colon or rectum: tumor invades muscularis propria or is more than 2 cm in size with invasion of lamina propria or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: T3, N0, M0. T3: Stomach: tumor penetrates subserosa; jejunum/ileum: tumor invades through the muscularis propria into subserosal tissue without penetration of overlying serosa or invades into non-peritonealized tissues; ampulla/duodenum: tumor invades pancreas or retroperitoneum or into non-peritonealized tissues; colon or rectum: tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: T4, N0, M0. T4: Stomach/duodenum/ampulla/jejunum/ileum: tumor invades visceral peritoneum (serosa) or invades other organs or adjacent structures; colon or rectum: tumor invades peritoneum or other organs. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: Any T, N1, M0. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
An injectable phospholipid emulsion containing the butyrate salt of the synthetic, short-acting, dihydropyridine L-type calcium channel antagonist clevidipine with antihypertensive activity. Clevidipine specifically binds to calcium channels in vascular smooth muscle cells, inhibiting the influx of extracellular calcium ions into vascular smooth muscle cells. This results in dilatation of systemic arteries, a decrease in systemic vascular resistance and so a decrease in arterial blood pressure. This agent is metabolized by esterases in the blood and extravascular tissues to an inactive carboxylic acid metabolite.
Stage IIIC includes: T4, N0, M0. T4: Tumors(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ (intraductal tumor). N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage I includes: T1, N0, M0. T1: Solitary tumor without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage II includes: T2, N0, M0. T2: Solitary tumor with vascular invasion or multiple tumors, with or without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage III includes: T3, N0, M0. T3: Tumor perforating the visceral peritoneum or involving the local extra hepatic structures by direct invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IVA includes: (T4, N0, M0); (Any T, N1, M0). T4: Tumor with periductal invasion. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 7th Ed.)
Stage IIIA includes: T3, N0, M0. T3: Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIIB includes: T1-3, N1, M0. T1: Tumor invades lamina propria or muscular layer. T2: Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver. T3: Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. N1: Metastases to nodes along the cystic duct, common bile duct, hepatic artery, and/or portal vein. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor confined to the bile duct, with extension up to the muscle layer or fibrous tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage II includes: T2a-b, N0, M0. T2a: Tumor invades beyond the wall of the bile duct to surrounding adipose tissue. T2b: Tumor invades adjacent hepatic parenchyma. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIIA includes: T3, N0, M0. T3: Tumor invades unilateral branches of the portal vein or hepatic artery. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIIB includes: T1-3, N1, M0. T1: Tumor confined to the bile duct, with extension up to the muscle layer or fibrous tissue. T2a: Tumor invades beyond the wall of the bile duct to surrounding adipose tissue. T2b: Tumor invades adjacent hepatic parenchyma. T3: Tumor invades unilateral branches of the portal vein or hepatic artery. N1: Regional lymph node metastasis (including nodes along the cystic duct, common bile duct, hepatic artery, and portal vein). M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IVA includes: T4, N0-1, M0. T4: Tumor invades the main portal vein or its branches bilaterally; or the common hepatic artery; or the second-order biliary radicals bilaterally; or unilateral second-order biliary radicals with contralateral portal vein or hepatic artery involvement. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis (including nodes along the cystic duct, common bile duct, hepatic artery, and portal vein). M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IVB includes: (Any T, N2, M0); (Any T, Any N, M1). N2: MetastasIs to periaortic, pericaval, superior mesenteric artery, and/or celiac artery lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (from AJCC 7th Ed.)
Stage IA includes: T1, N0, M0. T1: Tumor confined to the bile duct histologically. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IB includes: T2, N0, M0. T2: Tumor invades beyond the wall of the bile duct. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor invades the gallbladder, pancreas, duodenum, or other adjacent organs without involvement of the celiac axis or the superior mesenteric artery. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIB includes: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T1: Tumor confined to the bile duct histologically. T2: Tumor invades beyond the wall of the bile duct. T3: Tumor invades the gallbladder, pancreas, duodenum, or other adjacent organs without involvement of the celiac axis or the superior mesenteric artery. N1: Regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage III includes: T4, Any N, M0. T4: Tumor involves the celiac axis or the superior mesenteric artery. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IA includes: T1, N0, M0. T1: Tumor limited to ampulla of Vater or sphincter of Oddi. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IB includes: T2, N0, M0. T2: Tumor invades the duodenal wall. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor invades the pancreas. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIB includes: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T1: Tumor limited to ampulla of Vater or sphincter of Oddi. T2: Tumor invades the duodenal wall. T3: Tumor invades the pancreas. N1: Regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IA includes: T1, N0, M0. T1: Tumor limited to the pancreas, 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IB includes: T2, N0, M0. T2: Tumor limited to the pancreas, more than 2 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIB includes: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T1: Tumor limited to the pancreas, 2 cm or less in greatest dimension. T2: Tumor limited to the pancreas, more than 2 cm in greatest dimension. T3: Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery. N1: Regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage IIIa includes: T1-3, N1, M0. T1: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3-4) or tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated. T2: Tumor invades corpus spongiosum or cavernosum. T3: Tumor invades urethra. cN1: Palpable mobile unilateral inguinal lymph node. pN1: Metastasis in a single inguinal lymph node. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIb includes: T1-3, N2, M0. T1: Tumor invades subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3-4) or tumor invades subepithelial connective tissue with lymph vascular invasion or is poorly differentiated. T2: Tumor invades corpus spongiosum or cavernosum. T3: Tumor invades urethra. cN2: Palpable mobile multiple or bilateral inguinal lymph nodes. pN2: Metastasis in multiple or bilateral superficial inguinal lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIA includes: (T1a-c, N0, M0, PSA less than 20, Gleason 7); (T1a-c, N0, M0, PSA equal or more than 10 and less than 20, Gleason equal or less than 6); (T2a, N0, M0, PSA less than 20, Gleason equal or less than 7); (T2b, N0, M0, PSA less than 20, Gleason equal or less than 7); (T2b, N0, M0, PSA X, Gleason X). T1a: Tumor incidental histologic finding in 5% or less of tissue resected. T1b: Tumor incidental histologic finding in more than 5% of tissue resected. T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA). T2a: Tumor involves one-half of one lobe or less. T2b: Tumor involves more than one-half of one lobe, but not both lobes. cN0: No regional lymph node metastasis. pN0: No positive regional nodes. M0: No distant metastasis. Gleason 7: Moderately differentiated (moderate anaplasia). Gleason Equal or Less than 6: Well differentiated (slight anaplasia). (AJCC 7th ed.)
Stage IIB includes: (T2c, N0, M0, Any PSA, Any Gleason); (T1-2, N0, M0, PSA equal or more than 20, Any Gleason); (T1-2, N0, M0, Any PSA, Gleason equal or more than 8). T2c: Tumor involves both lobes. T1a: Tumor incidental histologic finding in 5% or less of tissue resected. T1b: Tumor incidental histologic finding in more than 5% of tissue resected. T1c: Tumor identified by needle biopsy (e.g., because of elevated PSA). T2a: Tumor involves one-half of one lobe or less. T2b: Tumor involves more than one-half of one lobe, but not both lobes. cN0: No regional lymph node metastasis. pN0: No positive regional nodes. M0: No distant metastasis. Gleason equal or more than 8: Poorly differentiated/undifferentiated (marked anaplasia). (AJCC 7th ed.)
Stage IA includes: T1, N0, M0. T1: Tumor 5 mm or less in greatest dimension. No invasion of the tarsal plate or eyelid margin. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IB includes: T2a, N0, M0. T2a: Tumor more than 5 mm, but not more than 10 mm in greatest dimension. Or, any tumor that invades the tarsal plate or eyelid margin. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IC includes: T2b, N0, M0. T2b: Tumor more than 10 mm, but not more than 20 mm in greatest dimension. Or, tumor involves full thickness of the eyelid. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T3a, N0, M0. T3a: Tumor more than 20 mm in greatest dimension. Or, any tumor that invades adjacent ocular or orbital structures. Or, any T with perineural tumor invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: T3b, N0, M0. T3b: Complete tumor resection requires enucleation, exenteration, or bone resection. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIC includes: T4, Any N, M0. T4: Tumor is not resectable due to extensive invasion of ocular, orbital, craniofacial structures, or brain. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIA includes: (T1b-d, N0, M0); (T2a, N0, M0). T1b: Iris: Tumor limited to the iris more than 3 clock hours in size. Ciliary body and choroid: Tumor size category 1 with ciliary body involvement. T1c: Iris: Tumor limited to the iris with secondary glaucoma. Ciliary body and choroid: Tumor size category 1 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. T1d: Ciliary body and choroid: Tumor size category 1 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. T2a: Iris: Tumor confluent with or extending into the ciliary body, choroid, or both, with secondary glaucoma. Ciliary body and choroid: Tumor size category 2 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIB includes: (T2b, N0, M0); (T3a, N0, M0). T2b: Ciliary body and choroid: Tumor size category 2 with ciliary body involvement. T3a: Iris: Tumor confluent with or extending into the ciliary body, choroid, or both, with sclera extension and secondary glaucoma. Ciliary body and choroid: Tumor size category 3 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: (T2c-d, N0, M0); (T3b-c, N0, M0); (T4a, N0, M0). T2c: Ciliary body and choroid: Tumor size category 2 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. T2d: Ciliary body and choroid: Tumor size category 2 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. T3b: Ciliary body and choroid: Tumor size category 3 with ciliary body involvement. T3c: Ciliary body and choroid: Tumor size category 3 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. T4a: Iris: Tumor with extrascleral extension less than or equal to 5 mm in diameter. Ciliary body and choroid: Tumor size category 4 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: (T3d, N0, M0); (T4b-c, N0, M0). T3d: Ciliary body and choroid: Tumor size category 3 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. T4b: Iris: Tumor with extrascleral extension more than 5 mm in diameter. Ciliary body and choroid: Tumor size category 4 with ciliary body involvement. T4c: Ciliary body and choroid: Tumor size category 4 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIC includes: T4d-e, N0, M0. T4d: Ciliary body and choroid: Tumor size category 4 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. T4e: Ciliary body and choroid: Any tumor size category with extraocular extension more than 5 mm in diameter. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
An electrocardiographic finding in which the cardiac rhythm is controlled by an electrical impulse from an artificial cardiac pacemaker. (CDISC)
A non-Hodgkin lymphoma arising from the conjunctiva, lacrimal gland, lacrimal drainage apparatus, eyelids, or other orbital tissues around the eye. The vast majority of cases are extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue, however, other histologic types of lymphomas can originate from ocular adnexal tissues, including rare cases of NK/T-cell lymphomas of nasal type.
Stage IA includes: T1, N0, M0, B0-1. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque +/- patch). N0: No clinically abnormal peripheral lymph nodes; biopsy not required. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 7th ed.)
Stage IB includes: T2, N0, M0, B0-1. T2: Patches, papules, or plaques covering 10% or more of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque +/- patch). N0: No clinically abnormal peripheral lymph nodes; biopsy not required. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 7th ed.)
Stage IIA includes: T1-2, N1-2, M0, B0-1. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque +/- patch). T2: Patches, papules, or plaques covering 10% or more of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque +/- patch). N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 7th ed.)
Stage IIB includes: T3, N0-2, M0, B0-1. T3: One or more tumors (equal or greater than 1 cm diameter). N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 7th ed.)
Stage IIIA includes: T4, N0-2, M0, B0. T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). (AJCC 7th ed.)
Stage IIIB includes: T4, N0-2, M0, B1. T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 7th ed.)
Stage IVA includes: IVA1 (T1-4, N0-2, M0, B2); IVA2 (T1-4, N3, M0, B0-2). T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque +/- patch). T2: Patches, papules, or plaques covering 10% or more of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque +/- patch). T3: One or more tumors (equal or greater than 1 cm diameter). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. B2: High blood tumor burden: 1000/microL Sezary cells or more with positive clone. (AJCC 7th ed.)
Stage IVB includes: T1-4, N0-3, M1, B0-2. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque +/- patch). T2: Patches, papules, or plaques covering 10% or more of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque +/- patch). T3: One or more tumors (equal or greater than 1 cm diameter). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. M1: Visceral involvement (must have pathology confirmation and organ involved should be specified). B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. B2: High blood tumor burden: 1000/microL Sezary cells or more with positive clone. (AJCC 7th ed.)
A finding about one or more characteristics of primary cutaneous lymphoma, following the rules of the TNM v7 classification system. Mycosis fungoides and Sezary syndrome have a formal staging system proposed by the International Society for Cutaneous Lymphomas (ISCL) and EORTC. The other cutaneous non-Hodgkin lymphomas are staged using the same system for lymphomas presenting in other anatomic locations. (from AJCC 7th Ed.)
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v7 classification system.
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor (skin).
Primary tumor cannot be assessed. (from AJCC 7th Ed.)
Limited patches, papules, and/or plaques covering less than 10% of the skin surface. May further stratify into T1a (patch only) vs. T1b (plaque +/- patch). Note: for skin, patch indicates any size skin lesion without significant elevation or induration. Presence/absence of hypo- or hyperpigmentation, scale, crusting, and/or poikiloderma should be noted. Plaque indicates any size skin lesion that is elevated or indurated. Presence or absence of scale, crusting, and/or poikiloderma should be noted. Histologic features such as folliculotropism or large-cell transformation (more than 25% large cells), CD30+ or CD30-, and clinical features such as ulceration are important to document. (from AJCC 7th Ed.)
Patches, papules, or plaques covering 10% or more of the skin surface. May further stratify into T2a (patch only) vs. T2b (plaque +/- patch). (from AJCC 7th Ed.)
One or more tumors (equal or greater than 1 cm diameter). Note: for skin, tumor indicates at least 1 cm diameter solid or nodular lesion with evidence of depth and/or vertical growth. Note total number of lesions, total volume of lesions, largest size lesion, and region of body involved. Also note if histologic evidence of large-cell transformation has occurred. Phenotyping for CD30 is encouraged. (from AJCC 7th Ed.)
Confluence of erythema covering 80% or more of body surface area. (from AJCC 7th Ed.)
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v7 classification system as they pertain to staging of peripheral lymph nodes.
No clinically abnormal peripheral lymph nodes; biopsy not required. Note: for node, abnormal peripheral lymph node(s) indicates any palpable peripheral node that on physical examination is firm, irregular, clustered, fixed or 1.5 cm or larger in diameter. Node groups examined on physical examination include cervical, supraclavicular, epitrochlear, axillary, and inguinal. Central nodes, which are not generally amenable to pathologic assessment, are not currently considered in the nodal classification unless used to establish N3 histopathology. (from AJCC 7th Ed.)
Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or NCI LN0-2. Note: Dutch grade 1: dermatopathic lymphadenopathy. NCI LN0: no atypical lymphocytes. NCI LN1: occasional and isolated atypical lymphocytes (not arranged in clusters). NCI LN2: many atypical lymphocytes or in 3-6 cell clusters. (from AJCC 7th Ed.)
Clone negative. Note: A T-cell clone is defined by PCR or Southern blot analysis of the T-cell receptor gene. (from AJCC 7th Ed.)
Clone positive. Note: A T-cell clone is defined by PCR or Southern blot analysis of the T-cell receptor gene. (from AJCC 7th Ed.)
Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. Note: Dutch grade 2: dermatopathic lymphadenopathy; early involvement by mycosis fungoides (presence of cerebriform nuclei greater than 7.5 micrometers). NCI LN3: aggregates of atypical lymphocytes; nodal architecture preserved. (from AJCC 7th Ed.)
Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. Note: Dutch grade 3: partial effacement of lymph node architecture; many atypical cerebriform mononuclear cells (CMCs). Dutch grade 4: complete effacement of lymph node. NCI LN4: partial/complete effacement of nodal architecture by atypical lymphocytes or frankly neoplastic cells. (from AJCC 7th Ed.)
Clinically abnormal peripheral lymph nodes; no histologic confirmation. (from AJCC 7th Ed.)
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases (visceral). (from AJCC 7th Ed.)
No visceral organ involvement. (from AJCC 7th Ed.)
Visceral involvement (must have pathology confirmation and organ involved should be specified). Note: for viscera, spleen and liver may be diagnosed by imaging criteria. (from AJCC 7th Ed.)
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v7 classification system as they pertain to peripheral blood involvement. (from AJCC 7th Ed.)
Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). Note: for blood, Sezary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If Sezary cells are not able to be used to determine tumor burden for B2, then one of the following modified ISCL criteria along with a positive clonal rearrangement of the TCR may be used instead: (1) expanded CD4+ or CD3+ cells with CD4/CD8 ratio of 10 or more, (2) expanded CD4+ cells with abnormal immunophenotype including loss of CD7 or CD26. (from AJCC 7th Ed.)
Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary) cells but does not meet the criteria of B2. (from AJCC 7th Ed.)
High blood tumor burden: 1000/microL Sezary cells or more with positive clone. Note 1: for blood, Sezary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If Sezary cells are not able to be used to determine tumor burden for B2, then one of the following modified ISCL criteria along with a positive clonal rearrangement of the TCR may be used instead: (1) expanded CD4+ or CD3+ cells with CD4/CD8 ratio of 10 or more, (2) expanded CD4+ cells with abnormal immunophenotype including loss of CD7 or CD26. Note 2: A T-cell clone is defined by PCR or Southern blot analysis of the T-cell receptor gene. (from AJCC 7th Ed.)
A finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A topical gel containing the Toll-like receptor (TLR) agonist resiquimod, an imidazoquinolinamine and with potential immunomodulating activity. Resiquimod binds toTLR7 and 8, mainly on dendritic cells, macrophages, and B-lymphocytes, and activates the TLR signaling pathway, resulting in the induction of the nuclear translocation of transcription activator NF-kB and activation of other transcription factors; subsequently, gene expression increases and the production of cytokines increases, especially interferon-alpha (INF-a), resulting in the enhancement of T-helper 1 (Th1) immune responses. In addition, topical application of resiquimod appears to activate epidermal Langerhans cells, leading to an enhanced activation of T-lymphocytes.
A cancer vaccine containing autologous dendritic cells electroporated with full-length mRNA encoding Wilms' tumor 1 (WT1) antigen with potential immunostimulatory and antineoplastic activities. Upon administration, WT1 mRNA-electroporated autologous dendritic cell vaccine may elicit a cytotoxic T-cell (CTL) response against tumor cells expressing WT1. Wt1 is frequently overexpressed in a variety of tumor cell types and often correlates with disease progression and poor prognosis.
An RGD-4C-modified, infectivity-enhanced, bicistronic type 5 adenovirus expressing herpes simplex virus thymidine kinase (HSV-tk) gene, a therapeutic suicide gene, and the somatostatin receptor type 2 (SSTR2) gene with potential antineoplastic activity. Modification with the double cyclic peptide RGD-4C allows the virus to bind to cellular integrins, frequently expressed on the surfaces of ovarian cancer cells, instead of the coxsackie and adenovirus (CAR) receptor, which is often nonfunctional in ovarian cancer cells. Upon intratumoral administration, Ad5.SSTR/TK.RGD transfects tumor cells and expresses the HSV-tk gene. After subsequent administration of a synthetic acyclic guanosine analogue prodrug like ganciclovir (GCV), expressed HSV-tk phosphorylates and activates the prodrug, which may result in inhibition of DNA synthesis and apoptosis in HSV-tk-expressing cancer cells. Additionally, as a bystander effect, adjacent non-transfected cells may be killed by the activated antiviral drug. SSTR2 expression allows imaging of gene transfer into tumor cells using a radiolabeled somatostatin analogue.
The progesterone derivative fluoro furanyl norprogesterone (FFNP), radiolabeled with fluorine F 18, with positron-emitting radioligand activity. Upon injection, fluorine F 18 fluoro furanyl norprogesterone (F18-FFNP) binds to progesterone receptors (PgR) in progesterone-responsive tissues. In PgR-positive breast cancer, positron emission tomography (PET) may then be used to quantitate hormone receptor status.
A formulation composed of DOTAP:cholesterol liposome nanoparticles complexed with the plasmid C-VISA BiKDD, with potential antineoplastic activity. C-VISA BikDD: liposome consists of a pancreatic-cancer-specific expression vector VISA (VP16-GAL4-WPRE integrated systemic amplifier) and a pancreatic-cancer-specific promoter CCKAR (cholecystokinin type A receptor) (CCKAR-VISA or C-VISA) which drives expression of the gene BikDD, a mutant form of the potent proapoptotic gene Bik (Bcl-2 interacting killer). Upon administration and transduction into pancreatic tumor cells, expression of BikDD by C-VISA BikDD:liposome may induce pancreatic tumor cell apoptosis and suppress pancreatic tumor cell proliferation. BikDD binds with greater affinity to anti-apoptotic proteins bcl-2, bcl-xl, bcl-w and Mcl-1 and is more potent than wild-type Bik. DOTAP:cholesterol liposome is composed of cationic lipid dioleoyl-trimethylammonium propane (DOTAP) and cholesterol at molar ratio of 1:1.
A radioconjugate consisting of the benzamide ligand ISO-1 labeled with the radioisotope fluorine F18 with positron-emitting radioisotope activity. Upon administration, fluorine [F18]ISO-1 binds to sigma-2 receptors, located on tumor cells, allowing visualization of sigma-2 receptor-expressing tumor cells with positron emission tomography (PET). Sigma-2 receptors, expressed in a variety of normal healthy tissues such as liver, kidneys, endocrine glands, and in the central nervous system, may be overexpressed in tumor cells.
An orally bioavailable quinoline-urea derivative inhibitor of vascular endothelial growth factor receptors (VEGFRs) 1 and 2 with potential antiangiogenesis and antineoplastic activities. VEGFR inhibitor KRN951 inhibits VEGF-induced phosphorylation of VEGFRs 1 and 2, which may result in inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and tumor cell death. Expression of VEGFRs may be upregulated in a variety of tumor cell types.
A dietary supplement containing an extract of the Basidiomycete fungus Agaricus blazei Murill with potential chemopreventive, antineoplastic and immunopotentiating activities. Agaricus blazei Murill extract contains high levels of phytochemicals, especially beta-D-glucans. Beta-D-glucans may promote dendritic cell (DC) maturation; increase interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and immunoglobulin levels; and may enhance natural killer (NK) cell activity, potentially boosting anti-tumor host immune responses.
A baker's yeast (Saccharomyces cerevisiae) containing high levels of the trace element selenium (Se) with potential chemopreventive, immunomodulating and antioxidant activities. Selenium is introduced into yeast during fermentation and incorporated into selenocompounds, such as selenomethionine and glutamyl SE methylselenocysteine. Selenium functions as a cofactor for antioxidant enzymes such as glutathione peroxidases and thioredoxin reductase.
An orally bioavailable, small-molecule, celecoxib-derived inhibitor of phosphoinositide-dependent kinase-1 (PDK1) with potential antineoplastic activity. Devoid of any COX inhibiting activity, PDK1 inhibitor AR-12 binds to and inhibits the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1).; subsequently, the phosphorylation and activation of the serine/threonine protein kinase Akt (protein kinase B or PKB) is inhibited, which may result in inhibition of the PI3K/Akt signaling pathway, inhibition of tumor cell proliferation, and the induction of tumor cell apoptosis. In addition, this agent appears to induce the activity of protein kinase R-like endoplasmic reticulum kinase (PERK), which plays a key role in the endoplasmic reticulum stress pathway. Activation and dysregulation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
An orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. FGFR inhibitor AZD4547 binds to and inhibits FGFR, which may result in the inhibition of FGFR-related signal transduction pathways, and, so, the inhibition of tumor cell proliferation and tumor cell death. FGFR, up-regulated in many tumor cell types, is a receptor tyrosine kinase essential to tumor cellular proliferation, differentiation and survival.
A second mitochondrial activator of caspases (Smac) mimetic inhibitor of IAPs (Inhibitor of Apoptosis Proteins) with potential antineoplastic activity. Smac mimetic GDC-0152 binds to the Smac binding groove on IAPs, including the direct caspase inhibitor X chromosome-linked IAP (XIAP) and the cellular IAPs 1 and 2, which may inhibit their activities and promote the induction of apoptosis through apoptotic signaling pathways. IAPs are overexpressed by many cancer cell types and suppress apoptosis by binding to and inhibiting active caspases-3, -7 and -9 via their baculoviral lAP repeat (BIR) domains. Smac, the endogenous IAP antagonist, relies on its N-terminal four amino-acid motif for binding to IAPs.
A proprietary, oral Chinese medicinal herb preparation with potential antioxidant, immunomodulating, and antineoplastic activities. THL-P (Tien-Hsien Liquid-P) contains fourteen Chinese medicinal herbs including: Cordyceps sinensis, Oldenlandia diffusa, Indigo pulverata levis, Polyporus umbellatus, Radix astragali, Panax ginseng, Solanum nigrum L., Pogostemon cablin, Atractylodis macrocephalae rhizoma, Trichosanthes radix, Clematis radix, Margarite, Ligustrum lucidum Ait and Glycyrrhiza radix. Administered as an oral liquid, THL-P may modulate the activity of natural killer (NK) cells, cytotoxic T-lymphocytes (CTLs), macrophages and polymorphonuclear leukocytes, and enhance the secretion of interleukins (ILs) and interferon-gamma (IFN-gamma). This agent may also induce G2/M cell cycle arrest and downregulate several important oncogenic signaling pathways.
A radioconjugate composed of the synthetic bombesin (BB) analog demobesin-4 bound to the radioisotope technetium Tc 99m with receptor ligand and gamma-emitting radioisotope activities. Upon intravenous administration, demobesin-4 selectively binds to the gastrin-releasing peptide receptor (GRPR) expressed on the surfaces of various tumor cell types; upon internalization, tumor cells expressing GRPRs bound to technetium Tc 99m can then be visualized using scintigraphy. GRPR, a bombesin receptor subtype, is frequently overexpressed on the surface of tumor cells such as prostate and breast cancer cells. Demobesin-4 was developed for technetium Tc 99m imaging of GRPR-expressing tumor cells.
A radioconjugate consisting of the somatostatin analogue edotreotide labeled with lutetium Lu 177 with potential antineoplastic activities. Lutetium Lu 177-edotreotide binds to somatostatin receptors (SSTRs), with high affinity to type 2 SSTR, present on the cell membranes of many types of neuroendocrine tumor cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR-positive cells. Edotreotide is produced by substituting tyrosine for phenylalanine at the 3 position of the somatostatin analogue octreotide (Tyr3-octreotide or TOC) and chelated by the bifunctional, macrocyclic chelating agent dodecanetetraacetic acid (DOTA).
A multikinase inhibitor with potential antineoplastic activity. Upon intravenous infusion, multikinase inhibitor SAR103168 may, through the inhibition of multiple kinases, inhibit the phosphorylation and activation of signal transducer and activator of transcription 5 (STAT5). STAT5, a protein often upregulated in cancer cells, plays a key role in signal transduction pathways and the suppression of apoptosis.
A cancer vaccine comprised of a recombinant modified vaccinia Ankara (MVA) viral vector encoding the suicide gene FCU1 with potential antineoplastic activity. FCU1 is a bifunctional yeast cytosine deaminase (CD) / uracil phosphoribosyltransferase (UPRT) fusion gene. Upon intratumoral administration, MVA-FCU1TG4023 enters tumor cells where FCU1 is expressed. Subsequently, the noncytotoxic prodrug 5-fluorocytosine (5-FC) is administered systemically and is deaminated by CD in FCU1- transduced tumor cells into 5-fluorouracil (5-FU), which is then directly metabolized to 5-fluoro-uridine monophosphate (5-FUMP) by UPRT; 5-FUMP may then be further transformed to 5-fluoro-deoxyuridine monophosphate (5-FdUMP), an irreversible inhibitor of thymidylate synthase and, so, DNA synthesis through deprivation of deoxythymidine triphosphate (dTTP). 5-FU and its active metabolites may then selectively kill tumor cells, avoiding toxicity in nonmalignant cells. The MVA viral vector, derived from the replication-competent strain Ankara, is a highly attenuated, replication-defective vaccinia strain incapable of virion assembly.
An orally bioavailable combination tablet containing the semisynthetic camptothecin derivative irinotecan and the multidrug resistance (MDR) efflux pump P-glycoprotein (P-gp) inhibitor HM30181AK, with potential antineoplastic activity. HM30181A binds to P-gp and prevents the P-gp-mediated efflux of irinotecan from tumor cells, which may result in greater intracellular concentrations of irinotecan and enhanced cytotoxicity. Retained intracellularly, the prodrug irinotecan is converted, by a carboxylesterase-converting enzyme, to the biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38). SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. P-gp, encoded by the MDR-1 gene, is a member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters and is overexpressed by some MDR tumors, preventing the intracellular accumulation of various cytotoxic agents.
A cream formulation containing aluminum chlorohydrate with astringent and antiperspirant activities. Upon topical application of F511 cream, aluminium chlorohydrate forms a gel matrix in the sweat gland which subsequently reduces, then stops the flow of water. In addition, this agent exerts an astringent effect, thereby further preventing sweat formation. Hyperhidrosis appears to play a role in the development of certain mucocutaneous reactions, such as palmar-plantar erythrodysesthesia (PPE), upon administration of chemotherapeutic agents such as doxorubicin, 5-fluorouracil, and capecitabine.
A humanized immunoglobulin IgG1 kappa monoclonal antibody directed against the B-cell-specific membrane protein CD-19 with potential immunostimulating and antineoplastic activities. Anti-CD19 monoclonal antibody MEDI-551 binds to CD19, which may result in a cytotoxic T-lymphocyte (CTL) response and antibody-dependent cellular cytotoxicity (ADCC) to CD19-expressing B-cells. The Fc portion of MEDI-551 does not contain a fucose sugar moiety, which may contribute to its enhanced ADCC activity. CD19 is a membrane antigen that is widely expressed during B-cell development, from pro-B-cell to early plasma cell stages.
A radioconjugate containing the nucleoside analog 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodouracil (FIAU) labeled with the radioisotope iodine I 124 with positron-emitting activity. Chemotherapeutic agents such as bortezomib may induce viral thymidine kinase expression in EBV- and Kaposi's sarcoma herpesvirus (KSHV)-associated tumors. Subsequent to chemotherapy induction of viral TK in these tumors, administered iodine I 124 FIAU is phosphorylated by expressed viral TK, becoming selectively trapped within TK-expressing tumor cells; these cells can then be visualized with positron emission tomography (PET). Viral TK is either not expressed or is expressed at very low levels in EBV- and Kaposi's sarcoma herpesvirus (KSHV)-associated tumors and may be activated by certain chemotherapeutic agents.
A recombinant human arginase I (liver arginase) covalently attached, via a succinamide propionic acid (SPA) linker, to a polyethylene glycol (PEG) of molecular weight 5,000 [rhArg-peg(5,000mw)] with potential antineoplastic activity. Upon intravenous administration of pegylated recombinant human arginase I BCT-100, arginase metabolizes the amino acid arginine to ornithine and urea, depleting intracellular arginine, which may inhibit proliferation of cells that are auxotrophic for arginine such as hepatocellular carcinoma (HCC) cells. This agent may also work synergistically with various cytotoxic agents.
An immunoconjugate containing a monoclonal antibody directed against the CD45 antigen BC8, conjugated to streptavidin, a nonglycosylated homotetrameric protein that has four high affinity binding sites for biotin. Anti-CD45 BC8 antibody-streptavidin conjugate binds to CD45, a transmembrane protein tyrosine phosphatase that is expressed on the surface of normal and malignant hematopoietic cells. Upon administration of a biotin-based radioconjugate, the biotin moiety of the radioconjugate binds to the streptavidin moiety of anti-CD45 BC8 antibody-streptavidin conjugate and, upon cellular internalization, specifically delivers cytotoxic radiation to CD45-expressing tumor cells.
A cancer vaccine consisting of the DNA plasmid pNGVL4a-A encoding calreticulin (CRT) linked to a detox form of human papillomavirus (HPV) type 16 E7 antigen, with potential immunomodulating and antineoplastic activities. Upon administration, this vaccine may generate a potent cytotoxic T-lymphocyte (CTL) response against E7-expressing tumor cells, resulting in tumor cell death. For E7(detox), the amino acids in E7 at positions 24 (cysteine to glycine) and 26 (glutamic acid to glycine) were substituted. CRT, a 46 kDa protein located in the lumen of the cell's endoplasmic reticulum (ER), may potentiate MHC class I presentation of HPV-16 E7 to E7-specific CD8-positive T cells. In addition, pNGVL4a-A contains two short immunostimulatory DNA sequences (ISS) in the noncoding region, which may elicit the production of IFN- and IL-12 in transfected keratinocytes and dermal antigen presenting cells (APCs), resulting in a potent T helper cell type 1 response.
A short chain fatty acid (SCFA) with potential herpes simplex virus thymidine kinase gene (HSV-TK)-inducing activity. Upon administration, short chain fatty acid HQK-1004 may induce the expression of thymidine kinase (TK) by a silenced HSV-TK, which may activate a co-administered antiviral prodrug such as ganciclovir, resulting in the destruction of virally-infected cancer cells.
A soluble fusion protein containing the extracellular domain of activin receptor-like kinase-1 (ALK1) fused to a human Fc domain (ALK1-Fc fusion protein), with potential antiangiogenic and antineoplastic activities. Upon administration, dalantercept binds to various ALK1 ligands, preventing activation of tumor cell ALK1 receptors and so inhibiting the ALK1 signaling pathway; growth factor-induced angiogenesis is thus inhibited, which may result in the inhibition of tumor cell proliferation and tumor cell death. ALK1 is a type I cell surface receptor with serine/threonine kinase activity that mediates signaling by members of the transforming growth factor-beta (TGFbeta) superfamily and plays a key role in angiogenesis; ligands for this receptor include TGFbeta1 and TGFbeta2. The Fc moiety of this fusion protein mediates clearance of ligand-fusion protein complexes by the reticuloendothelial system (RES).
A juice containing tomato extract and soy protein with potential chemopreventive and antiproliferative activities. Tomato-soy juice contains phytochemicals, including flavonoids, such as the soy isoflavone genistein, and carotenoids, including lycopene. These phytochemicals may exhibit antioxidative activity, antitumor activity by modulating certain tumor-associated signal transduction pathways, and apoptosis-inducing activity.
A fusion protein containing angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) derived peptides covalently attached, via a proprietary diketone linker, to a proprietary humanized catalytic aldolase monoclonal antibody, with potential antiangiogenic and antineoplastic activities. The Ang2/VEGF peptide moieties of Ang2/VEGF-binding peptides-antibody fusion protein CVX-241 bind to Ang2 and VEGF receptors, which may inhibit tumor angiogenesis and tumor cell proliferation. The proprietary humanized catalytic IgG1 monoclonal aldolase antibody contains reactive lysine residues in its binding sites, which react covalently with compounds having a diketone function; the Ang2 and VEGFR peptide moieties are then covalently attached to the diketone linkers via a proprietary spacer. Both VEGF and Ang2 are upregulated in a variety of cancer cell types and play a crucial role in angiogenesis. This agent possesses an enhanced half-life compared to the naked peptides.
The sodium salt of an acyl-sulfonamide with potential antineoplastic activity. Selectively toxic towards tumor cells, tasisulam appears to induce tumor cell apoptosis by a mitochondrial-targeted mechanism involving the loss of mitochondrial membrane potential and induction of reactive oxygen species (ROS). In combination with an angiogenesis inhibitor, this agent may exhibit synergistic antiangiogenic activity.
A crosslinked nanoparticle formulation containing quaternary ammonium polyethylenimine (QA-PEI) with potential antibacterial activity. The cationic polymer PEI kills bacteria by rupturing their cell membranes without the development of resistance. Quaternary ammonium polyethylenimine nanoparticles can be incorporated into dental composite resins or silicon obturator prostheses and may prevent or delay bacterial growth.
A recombinant immunotoxin consisting of single-chain variable domain fragment antibody directed against the tumor-specific antigen EGFRvIII (MR1scFv) fused to domains II and III of the Pseudomonas exotoxin (PE38KDEL), with potential antineoplastic activity. Upon administration, the antibody moiety of anti-EGFRvIII immunotoxin MR1-1 binds to EGFRvIII; upon internalization, the exotoxin portion inhibits protein synthesis, resulting in a reduction in tumor cell proliferation of EGFRvIII- expressing tumor cells. EGFRvIII, a type III in-frame deletion mutation of the epidermal growth factor receptor (EGFR) gene, is expressed by a variety of cancers, including glioblastoma multiforme, non-small lung carcinoma, and breast carcinoma. Compared to intact IgG antibodies, single-chain antibodies such as MR1scFv are smaller and may penetrate tumors better. Pseudomonas exotoxin PE38KDEL was modified to remove the natural cell binding domain.
A population of allogeneic cytotoxic T lymphocytes (CTLs) specifically reactive to cytomegalovirus (CMV) and adenovirus (AdV) with potential antiviral activity. Allogeneic CMV/AdV-specific cytotoxic T lymphocytes are prepared by exposing donor-derived CTLs to a lethally irradiated Epstein-Barr virus-positive lymphoblastoid B cell line (EBV-LCL) that has been transduced with a clinical-grade adenoviral vector (Ad5f35CMVpp65) as a source of CMV and AdV antigens. Infusion of these CTLs into stem cell transplant recipients may prevent CMV and AdV viral disease.
An orally bioavailable, small-molecule Polo-like kinase 1 (PLK1) inhibitor with potential antineoplastic activity. Polo-like kinase 1 inhibitor NMS-1286937 selectively inhibits PLK1, inducing selective G2/M cell-cycle arrest followed by apoptosis in a variety of tumor cells while causing reversible cell-cycle arrest at the G1 and G2 stages without apoptosis in normal cells. PLK1 inhibition may result in the inhibition of proliferation in PLK1-overexpressing tumor cells. PLK1 is a serine/threonine protein kinase crucial in the regulation of mitosis.
An orally bioavailable cell division cycle 7 homolog (CDC7) kinase inhibitor with potential antineoplastic activity. CDC7 kinase inhibitor NMS-1116354 binds to and inhibits the activity of CDC7, which may result in the inhibition of DNA replication and mitosis, the induction of tumor cell apoptosis, and the inhibition of tumor cell proliferation in CDC7-overexpressing tumor cells. The serine-threonine kinase CDC7 initiates DNA replication by phosphorylating MCM2 (minichromosome maintenance complex component 2) at Ser40 and Ser53.
Activated T cells (ATC) that have been coated with bispecific antibodies (BiAb), with potential antineoplastic and immunomodulating activities. In vitro, T cells are activated through exposure to the anti-CD3 murine monoclonal antibody OKT3 and interleukin 2 for 14 days and then armed with anti-CD3 x anti-Her2 bispecific antibody (Her2Bi). Upon administration, HER2Bi-armed activated T cells attach to CD3-expressing T cells and HER2/neu-expressing tumor cells, selectively cross-linking T cells and tumor cells; this may result in the recruitment and activation of cytotoxic T lymphocyte (CTLs), CTL perforin-mediated tumor cell cytolysis, and the secretion of antitumor cytokines and chemokines.
A non-engineered, naturally oncolytic, replication-competent spontaneous herpes simplex virus (HSV) type I mutant variant. Upon intratumoral injection, HSV1 HF10 transfects, replicates in, and lyses rapidly dividing cells such as tumor cells. In addition, this agent may increase host immune responses that may kill non-infected tumor cells.
A radiopharmaceutical containing the serotonin transporter (SERT) ligand ADAM [2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine] labeled with the radioisotope iodine I 123, with SERT-binding and radioisotope activities. Upon administration, iodine I 123 ADAM selectively binds to SERT-expressing cells; subsequently, SERT-expressing tissues may be visualized using single photon emission computed tomography (SPECT). SERT is a monamine transporter protein found in the membranes of neurons and platelets; in neurons it transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons, terminating serotonin's function.
A split-virus, inactivated influenza A (H1N1) vaccine containing H1N1 immunizing antigen combined with the adjuvant AS03, with potential immunostimulating activity. Upon intramuscular vaccination, AS03-adjuvanted H1N1 influenza vaccine may elicit an immune response against the H1N1 virus and the production of anti-H1N1 antibodies. AS03 is a stabilized oil-in-water emulsion adjuvant containing DL-alpha-tocopherol, squalene and polysorbate 80 that non-specifically stimulates cell-mediated immune antigen responses.
A polymeric prodrug consisting of the fumagillol-derived small molecule XMT-1191 tethered to the hydrophilic, biodegradable70 kDa polymer poly[1-hydroxymethylethylene hydroxymethylformal] (PHF) with potential antiangiogenic and antineoplastic activities. Upon administration, fumagillin-derived polymer conjugate XMT-1107 releases XMT-1191, which may inhibit angiogenesis through the irreversible inhibition of the methionine aminopeptidase 2 (METAP2); although the exact mechanism of action has yet to be fully elucidated, this agent appears to induce cell cycle arrest in endothelial cells, inhibiting their proliferation and migration. Compared to an unconjugated fumagillin analog, XMT-1107 exhibits improved solubility and an extended half life due to its PHF backbone. METAP2, a member of the methionyl aminopeptidase family, binds two cobalt or manganese ions and protects the alpha subunit of eukaryotic initiation factor 2 (EIF2) from inhibitory phosphorylation by removing the amino-terminal methionine residue from nascent protein; this aminopeptidase may be overexpressed in a variety of tumor cell types.
An injectable formulation containing the taxane docetaxel, a semisynthetic analogue of paclitaxel, with antineoplastic activity. Docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response.
A reversible small-molecule inhibitor of activated factor VII (factor VIIa) with potential antineoplastic and antithrombotic activities. FVII, a serine protease, becomes activated (FVIIa) upon binding with TF forming the FVIIa/TF complex, which induces intracellular signaling pathways by activating protease activated receptor 2 (PAR-2). Upon subcutaneous administration, factor VIIa inhibitor PCI-27483 selectively inhibits factor FVIIa in the VIIa/TF complex, which may prevent PAR-2 activation and PAR2-mediated signal transduction pathways, thereby inhibiting tumor cell proliferation, angiogenesis, and metastasis of TF-overexpressing tumor cells. In addition, this agent inhibits both the extrinsic and intrinsic coagulation cascades, preventing blood clot formation. TF, a blood protein overexpressed on the cell surface of a variety of tumor cell types, may correlate with poor prognosis; PAR-2 (also known as thrombin receptor-like 1) is a G protein-coupled receptor (GPCR) and a protease-activated receptor.
A human IgG1 monoclonal antibody directed against interleukin-1 alpha (IL1a) with potential A human IgG1 monoclonal antibody targeting the inflammatory cytokine interleukin-1 alpha (IL1a) with potential antineoplastic, anti-cachectic and anti-angiogenic activities. Anti-IL1a monoclonal antibody MABp1 targets and binds to IL1a and prevents IL1a activity. This prevents IL1a-mediated tumorigenesis and angiogenesis. In addition, MABp1 abrogates IL1a-mediated cachexia. IL1a, an inflammatory mediator expressed on monocytes, platelets and overexpressed by certain tumors, plays a key role in the promotion of tumor cell growth, metastasis and invasion. In addition, IL1a stimulates metabolic activity in the central nervous system.
A vaccine consisting of recombinant modified vaccinia Ankara (MVA) viral vector encoding mutated forms of the genes for the viral oncoproteins E6 and E7 derived from the human papillomavirus (HPV) type 16 and the human cytokine interleukin-2 (hIL2), with potential immunomodulating and antineoplastic activities. Upon subcutaneous administration, recombinant vaccinia viral vector RO5217790 may stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against cells expressing HPV E6 and E7, resulting in tumor cell lysis. Oncoproteins E6 and E7 have been implicated in the tumorigenesis of cervical carcinoma.
A fully human IgG1 monoclonal antibody directed against intercellular adhesion molecule-1 (ICAM-1 or CD54), with potential antineoplastic activity. Anti-ICAM-1 monoclonal antibody BI-505 selectively binds to the adhesion protein ICAM-1, which may result in antibody-dependent cellular cytotoxicity (ADCC), hyper-cross-linking-induced apoptosis, and a decrease in cellular proliferation of ICAM-1-expressing tumor cells. ICAM-1, normally expressed on leukocytes and endothelial cells, may be overexpressed in a variety of cancers.
An inhibitor of the kinesin-related motor protein Eg5 with potential antineoplastic activity. Litronesib selectively inhibits the activity of Eg5, which may result in mitotic disruption, apoptosis and consequently cell death in tumor cells that are actively dividing. The ATP-dependent Eg5 kinesin-related motor protein (also known as KIF11 or kinesin spindle protein-5) is a plus-end directed kinesin motor protein that plays an essential role during mitosis, particularly in the regulation of spindle dynamics, including assembly and maintenance.
A second generation, replication-competent adenovirus type 5 containing a yeast cytosine deaminase(yCD)/mutant sr39 herpes simplex virus thymidine kinase fusion (yCD/mutTKsr39) gene and the 11.6 kDa adenovirus death protein (ADP) gene with potential oncolytic activity. Upon intratumoral administration and transduction of Ad5-yCD/mutTK(SR39)rep-ADP into tumor cells and subsequent expression of cytosine deaminase and viral thymidine kinase, administered prodrugs 5-fluorocytosine (5-FC) and ganciclovir are converted into their respective metabolites 5-fluorouracil (5-FU) and ganciclovir-5-monophosphate (ganciclovir-MP); 5-FU is subsequently metabolized to cytotoxic active metabolites 5-fluoroxyuridine monophosphate (F-UMP) and 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate (F-dUMP); ganciclovir-TP subsequently is converted by mammalian thymidine kinase to cytotoxic ganciclovir-triphosphate (ganciclovir -TP). Tumor cells adjacent to tumor cells transduced with this agent may be killed through a 'bystander effect'. ADP may enhance spread and oncolytic activity of replication-competent adenoviruses. In addition to its oncolytic activity, Ad5-yCD/mutTK(SR39)rep-ADP may exhibit radiosensitizing activity.
A monovalent vaccine containing hemagglutinin (HA) of influenza A (H1N1)-like virus with potential immunomodulating activity. Upon administration, non-adjuvanted A(H1N1) influenza vaccine may stimulate the immune system to mount an antibody response against H1N1.
A 20-mer antisense oligodeoxynucleotide (ODN) against the proto-oncogene Akt with potential antineoplastic activity. Akt-1 antisense oligonucleotide RX-0201 binds to Akt-1 mRNA, inhibiting translation of the transcript; suppression of Akt-1 expression may result in the inhibition of cellular proliferation and the induction of apoptosis in tumor cells that overexpress Akt-1. Akt-1 is a serine-threonine protein kinase that stimulates proliferation and inhibits apoptosis of tumor cells.
Holmium Ho166 containing poly l-lactic acid (PLA) microspheres with potential antineoplastic actvity. Upon intra-arterial hepatic administration of holmium 166 microspheres, this agent is able to emit both beta particles direct killing cells and gamma photons for nuclear imaging. In addition, since holmium 166 is paramagnetic, this agent can be used for magnetic resonance imaging (MRI).
A topical formulation of the small-molecule Smoothened (Smo) antagonist LDE225 with potential antineoplastic activity. Upon topical application, smoothened antagonist LDE225 selectively binds to the Hedgehog (Hh)-ligand cell surface receptor Smo, which may result in the suppression of the Hh signaling pathway and, so, the inhibition of tumor cells in which this pathway is abnormally activated. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair. Inappropriate activation of Hh pathway signaling and uncontrolled cellular proliferation, as is observed in a variety of cancers, may be associated with mutations in the Hh-ligand cell surface receptor Smo.
A benzofuran-based vascular disrupting agent (VDA) prodrug with potential anti-vascular and antineoplastic activities. Upon administration vascular disrupting agent BNC105P, the disodium phosphate ester of BNC105, is rapidly converted to BNC105; in activated endothelial cells, BNC105 binds to tubulin and inhibits its polymerization, which may result in a blockage of mitotic spindle formation, cell cycle arrest, and disruption of the tumor vasculature. Hypoxic conditions ensue, depriving tumor cells of nutrients and resulting in tumor cell apoptosis. In addition to its VDA activity, this agent has a direct cytotoxic effect on tumor cells by inhibiting tubulin polymerization. BNC105 is not a substrate for the multidrug-resistance P-glycoprotein (Pgp) transporter.
A topical formulation consisting of a polyvinylidene fluoride (PVDF) polymer resin containing the macrolide sirolimus (rapamycin), produced by the organism Streptomyces hygroscopicus, with immunosuppressive activity. Upon application of topical PVDF/sirolimus, sirolimus migrates from the PVDF polymer resin into the skin. Once inside cells, sirolimus binds to the immunophilin FK binding protein-12 (FKBP-12) and forms a sirolimus:FKBP-12 complex. This complex binds to and inhibits the activity of the serine/threonine kinase mammalian target of rapamycin (mTOR), which may result in the suppression of cytokine-driven T-cell activation and proliferation.
A hapten-carrier immunoconjugate composed of the hapten trans-3'-aminomethyl nicotine conjugated to a recombinant P. aeruginosa exoprotein A, rendered nontoxic through amino acid depletion, with potential immunostimulating activity. Upon vaccination with 3'-aminomethyl nicotine-P. aeruginosa r-exoprotein A conjugate vaccine, the immune system may produce anti-nicotine antibodies. Antibody-bound nicotine cannot pass the blood brain barrier (BBB) to activate brain nicotine receptors. Nicotine, a small organic molecule that is not immunogenic, must be haptenized and conjugated to a carrier protein, such as nontoxic recombinant P. aeruginosa exoprotein A, to induce an antibody response. Aluminium hydroxide may be used as an adjuvant for this vaccine.
A synthetic, 21-mer, unmethylated CpG motif-based oligodeoxynucleotide (ODN), with immunostimulatory activity. CpG oligodeoxynucleotide GNKG168 binds to and activates Toll-like receptor 9 (TLR9) and is taken up into cells by endocytosis; once internalized, it may activate numerous signaling transduction pathways resulting in the release of multiple cytokines, such as immunoglobulins (Igs), interferons (IFNs), interleukins (ILs) and tumor necrosis factor (TNF). Through activation of TLR9, this ODN can directly stimulate B-lymphocytes, dendritic and natural killer (NK) cells, resulting in an increase in innate immunity and antibody-dependent cellular cytotoxicity (ADCC). In addition, through the release of IL-12 and IFN, this agent may induce a preferential shift to the T-helper 1(Th1) phenotype resulting in enhanced CD8+ T cell-mediated antitumor cytotoxicity.
A meso-tetraphenylchlorin substituted by two adjacent sulfonated groups with potential photosensitizing activity. Upon administration, tetraphenyl chlorin disulfonate incorporates into the cell's endosome and lysosome membranes. Subsequently, cytotoxic agents are administered and accumulate in endosomal and lysosomal compartments; upon local activation by light, tetraphenyl chlorin disulfonate produces reactive oxygen species (ROS), such as singlet oxygen, damaging endo/lysosomal membranes and accumulated cytotoxic agents are released into the tumor cell cytosol. This photochemical internalization (PCI) method can enhance the efficacy and selectivity of cytotoxic agents.
A focal adhesion kinase-1 (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. FAK inhibitor GSK2256098 inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including ERK, JNK/MAPK and PI3K/Akt, thereby inhibiting tumor cell migration, proliferation and survival, and tumor angiogenesis. The tyrosine kinase FAK is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. The TNM pathologic and clinical primary tumor classifications of breast cancer are the same, regardless of whether they are based on pathologic and/or clinical criteria.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. The classification is based on axillary lymph node dissection with or without sentinel lymph node biopsy. (partially adapted from AJCC 7th Ed.)
Breast cancer without histological evidence of regional lymph node involvement. Lymph nodes containing only isolated tumor cell clusters are excluded from the total positive node count for purposes of regional lymph node classification, but should be included in the total number of nodes evaluated. (from AJCC 7th Ed.)
Breast cancer without histological evidence of regional lymph node involvement, and with negative immunohistochemistry. (from AJCC 7th Ed.)
Breast cancer with malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or immunohistochemistry including isolated tumor cell clusters). (from AJCC 7th Ed.)
Breast cancer with micrometastases; or metastases in 1 to 3 axillary lymph nodes; and/or metastases in internal mammary nodes, with the metastases detected by sentinel lymph node biopsy but not clinically detected. ""Not clinically detected"" is defined by imaging studies (excluding lymphoscintigraphy) or by clinical examination. (from AJCC 7th Ed.)
Breast cancer with micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm) (from AJCC 7th Ed.)
Breast cancer with metastases in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected. ""Not clinically detected"" is defined by imaging studies (excluding lymphoscintigraphy) or by clinical examination. (from AJCC 7th Ed.)
Breast cancer with metastases in 1 to 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected. ""Not clinically detected"" is defined by imaging studies (excluding lymphoscintigraphy) or by clinical examination. (from AJCC 7th Ed.)
Breast cancer with metastases in 4 to 9 axillary lymph nodes, or metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases. ""Clinically detected"" is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination. (from AJCC 7th Ed.)
Breast cancer with metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node metastases. ""Clinically detected"" is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination. (from AJCC 7th Ed.)
Breast cancer with metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or in clinically detected ipsilateral internal mammary lymph nodes in the presence of 1 or more positive level I, II axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected; or in ipsilateral supraclavicular lymph nodes. (from AJCC 7th Ed.)
Breast cancer with metastases in clinically detected ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. TNM pathologic distant metastasis findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, endoscopy, biopsy or laboratory testing.
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. The TNM clinical and pathologic primary tumor classifications of breast cancer are the same, regardless of whether they are based on clinical and/or pathologic criteria.
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Breast cancer with metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted; or in clinically detected ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases. ""Clinically detected"" is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination. (from AJCC 7th Ed.)
Breast cancer with metastases only in clinically detected ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary lymph node metastases. ""Clinically detected"" is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination and having characteristics highly suspicious for malignancy or a presumed pathologic macrometastasis based on fine needle aspiration biopsy with cytologic examination. (from AJCC 7th Ed.)
Breast cancer with metastases in ipsilateral infraclavicular (level III) axillary lymph node(s) with or without level I, II axillary lymph node involvement; or in clinically detected ipsilateral internal mammary lymph node(s) with clinically evident level I, II axillary lymph node metastases; or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Breast cancer in which there is no clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are no larger than 0.2 mm in a patient without symptoms or signs of metastases. (from AJCC 7th Ed.)
Breast cancer in which there is no clinical or radiographic evidence of distant metastases. (from AJCC 7th Ed.)
Breast cancer with distant detectable metastases as determined by classic clinical and radiographic means and/or histologically proven larger than 0.2 mm. (from AJCC 7th Ed.)
A finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v7 classification system. The TNM clinical and pathologic regional lymph nodes tumor classifications of cutaneous melanoma are not the same. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v7 classification system. TNM pathologic findings are based on histopathologic examination of one or more tissue specimens acquired during surgery. The TNM pathologic and clinical regional lymph nodes tumor classifications of cutaneous melanoma are not the same. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. The TNM pathologic and clinical primary tumor classifications of cutaneous melanoma are the same. (from AJCC 7th Ed.)
Cutaneous melanoma in which the primary tumor cannot be assessed (e.g., curettaged or severely regressed melanoma). (from AJCC 7th Ed.)
Cutaneous melanoma with a tumor measuring 1.0 mm or less in thickness. (from AJCC 7th Ed.)
Cutaneous melanoma with a tumor measuring 1.0 mm or less in thickness, without ulceration and with mitosis less than 1/mm2. (from AJCC 7th Ed.)
Cutaneous melanoma with a tumor measuring 1.0 mm or less in thickness, with ulceration or mitoses equal to or more than 1/mm2. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM classification system as they pertain to staging of regional lymph nodes. The TNM clinical and pathologic regional lymph nodes tumor classifications of cutaneous melanoma are not the same. TNM pathologic findings are based on the pathologic examination of the regional lymph nodes after sentinel or complete lymphadenectomy. (from AJCC 7th Ed.)
Cutaneous melanoma in which the regional lymph nodes cannot be assessed (e.g., previously removed for another reason). (from AJCC 7th Ed.)
Cutaneous melanoma with metastasis in one regional lymph node. (from AJCC 7th Ed.)
Cutaneous melanoma with micrometastasis in one regional lymph node. Micrometastases are diagnosed after sentinel lymph node biopsy and completion of lymphadenectomy (if performed). (from AJCC 7th Ed.)
Cutaneous melanoma with macrometastasis in one regional lymph node. Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension. (from AJCC 7th Ed.)
Cutaneous melanoma with metastases in 2-3 regional lymph nodes or in transit met(s)/satellite(s) without metastatic nodes. (from AJCC 7th Ed.)
Cutaneous melanoma with micrometastases in 2-3 regional lymph nodes. Micrometastases are diagnosed after sentinel lymph node biopsy and completion of lymphadenectomy (if performed). (from AJCC 7th Ed.)
Cutaneous melanoma with macrometastases in 2-3 regional lymph nodes. Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or when nodal metastasis exhibits gross extracapsular extension. (from AJCC 7th Ed.)
Cutaneous melanoma with intralymphatic metastases (in transit or satellite metastases) without metastatic nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for cutaneous melanoma. (from AJCC 7th Ed.)
Cutaneous melanoma with detectable evidence of distant metastases. (from AJCC 7th Ed.)
Cutaneous melanoma with metastases to skin, subcutaneous tissues, or distant lymph nodes associated with normal serum lactate dehydrogenase (LDH). (from AJCC 7th Ed.)
Cutaneous melanoma with metastases to lung associated with normal serum lactate dehydrogenase (LDH). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v7 classification system. TNM clinical findings are based on clinical/radiographic examinations. The TNM clinical and pathologic primary tumor classifications of cutaneous melanoma are the same. The TNM clinical and pathologic regional lymph nodes tumor classifications of cutaneous melanoma are not the same. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM classification system as they pertain to staging of regional lymph nodes. The TNM clinical and pathologic regional lymph nodes classifications of cutaneous melanoma are not the same. TNM clinical regional lymph nodes findings are based on clinical/radiographic exam of the regional lymph nodes. (from AJCC 7th Ed.)
Cutaneous melanoma in which no regional metastases are detected. (from AJCC 7th Ed.)
Cutaneous melanoma with 1 or more metastatic nodes with in transit met(s)/satellite(s). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. The clinical distant metastasis TNM findings for cutaneous melanoma include M0, M1a, M1b, and M1c. (from AJCC 7th Ed.)
Cutaneous melanoma with no detectable evidence of distant metastases. (from AJCC 7th Ed.)
Cutaneous melanoma with metastases to all other visceral sites associated with normal serum lactate dehydrogenase (LDH) or distant metastases to any site associated with an elevated serum LDH. (from AJCC 7th Ed.)
Stage I includes: IA: (T1a, N0, M0); IB: (T1b, N0, M0); (T2a, N0, M0). T1a: Cutaneous melanoma with a tumor measuring 1.0 mm or less in thickness, without ulceration and mitosis less than 1/mm2. T1b: Cutaneous melanoma with a tumor measuring 1.0 mm or less in thickness, with ulceration or mitoses equal to or more than 1/mm2. T2a: Cutaneous melanoma with a tumor measuring 1.01-2.0 mm in thickness, without ulceration. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 7th Ed.)
Stage III includes: Any T, N1-3, M0. Stage III is divided into three pathologic subgroups: IIIA, IIIB, and IIIC. There are no clinical subgroups for stage III. N1: Cutaneous melanoma with metastasis in one regional lymph node. N2: Cutaneous melanoma with metastases in 2-3 regional lymph nodes or in transit met(s)/satellite(s) without metastatic nodes. N3: Cutaneous melanoma with 4 or more metastatic nodes, or matted nodes, or in transit met(s)/satellite(s) with metastatic node(s). M0: No detectable evidence of distant metastases. (from AJCC 7th Ed.)
A finding about one or more characteristics of musculoskeletal system cancer, following the rules of the TNM AJCC v7 classification system. This classification is used for all primary malignant tumors of bone (except primary malignant lymphoma and multiple myeloma) and soft tissue sarcoma. (from AJCC 7th Ed.)
A finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v7 classification system. This classification is used for all primary malignant tumors of bone except primary malignant lymphoma and multiple myeloma. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v7 classification system. The pathologic diagnosis is based on the microscopic examination of tissue, correlated with imaging studies. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Bone cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Bone cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Bone cancer with tumor measuring 8 cm or less in greatest dimension. (from AJCC 7th Ed.)
Bone cancer with tumor measuring more than 8 cm in greatest dimension. (from AJCC 7th Ed.)
Bone cancer with discontinuous tumors in the primary bone site. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Bone cancer in which regional lymph nodes cannot be assessed. Note: Because of the rarity of lymph node involvement in bone sarcomas, the designation NX may not be appropriate and cases should be considered N0 unless clinical node involvement is clearly evident. (from AJCC 7th Ed.)
Bone cancer without regional lymph node metastasis. (from AJCC 7th Ed.)
Bone cancer with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for bone cancer.
Bone cancer with distant metastasis. (from AJCC 7th Ed.)
Bone cancer with metastasis to lung. (from AJCC 7th Ed.)
Bone cancer with metastasis to other distant sites. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v7 classification system. The clinical staging includes all relevant data prior to primary definitive therapy, including physical examination, imaging, and biopsy. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Bone cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of soft tissue sarcoma, following the rules of the TNM AJCC v7 classification system. Kaposi sarcoma, fibromatosis (desmoid tumor), and sarcoma arising from the dura mater, brain, parenchymatous organs, or hollow viscera are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of soft tissue sarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Soft tissue sarcoma in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Soft tissue sarcoma with no evidence of primary tumor. (from AJCC 7th Ed.)
Soft tissue sarcoma with tumor measuring 5 cm or less in greatest dimension. (from AJCC 7th Ed.)
Soft tissue sarcoma with superficial tumor measuring 5 cm or less in greatest dimension. (from AJCC 7th Ed.)
Soft tissue sarcoma with deep tumor measuring 5 cm or less in greatest dimension. (from AJCC 7th Ed.)
Soft tissue sarcoma with tumor measuring more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
Soft tissue sarcoma with superficial tumor measuring more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
Soft tissue sarcoma with deep tumor measuring more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Soft tissue sarcoma in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Soft tissue sarcoma without regional lymph node metastasis. (from AJCC 7th Ed.)
Soft tissue sarcoma with regional lymph node metastasis. Note: Presence of positive nodes (N1) in M0 tumors is considered Stage III. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for soft tissue sarcoma.
Soft tissue sarcoma with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of soft tissue sarcoma, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of soft tissue sarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Soft tissue sarcoma without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of skin carcinoma, following the rules of the TNM AJCC v7 classification system. It applies to skin squamous cell carcinoma, Merkel cell carcinoma, and other nonmelanoma skin carcinomas. (from AJCC 7th Ed.)
A finding about one or more characteristics of skin squamous cell carcinoma or other nonmelanoma skin carcinomas excluding Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of skin squamous cell carcinoma or other skin carcinomas excluding Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system. TNM pathologic findings are based on histopathologic examination of one or more tissue specimens acquired during surgery. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of skin squamous cell carcinoma or other skin carcinomas, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. It excludes cutaneous squamous cell carcinoma of the eyelid and Merkel cell carcinoma. The TNM pathologic and clinical primary tumor classifications of skin squamous cell carcinoma or other skin carcinomas are the same. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with no evidence of primary tumor. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with a tumor size 2 cm or less in greatest dimension with less than two high-risk features. High-risk features for the primary tumor staging are defined as follows: depth/invasion of more than 2 mm thickness; Clark level equal to or greater than IV; and perineural invasion. Anatomic location: primary site ear and primary site non-hair-bearing lip. Differentiation: poorly differentiated or undifferentiated. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with a tumor size greater than 2 cm in greatest dimension or tumor of any size with two or more high-risk features. High-risk features for the primary tumor staging are defined as follows: depth/invasion of more than 2 mm thickness; Clark level equal to or greater than IV; and perineural invasion. Anatomic location: primary site ear and primary site non-hair-bearing lip. Differentiation: poorly differentiated or undifferentiated. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with tumor invasion of maxilla, mandible, orbit, or temporal bone. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with tumor invasion of skeleton (axial or appendicular) or perineural invasion of skull base. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of skin squamous cell carcinoma or other skin carcinomas, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. The TNM pathologic and clinical regional lymph nodes classifications of skin squamous cell carcinoma or other skin carcinomas are the same. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas without regional lymph node metastases. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with metastasis in a lymph node, more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of skin squamous cell carcinoma or other skin carcinomas, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas with distant metastases. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of skin squamous cell carcinoma or other skin carcinomas, following the rules of the TNM AJCC v7 classification system. TNM clinical findings are based on inspection and palpation of the involved area and the regional lymph nodes. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of skin squamous cell carcinoma or other skin carcinomas, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. (from AJCC 7th Ed.)
Skin squamous cell carcinoma or other skin carcinomas without distant metastases. (from AJCC 7th Ed.)
A finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system. TNM pathologic findings are based on the histologic examination of the regional lymph nodes following focused (sentinel lymph node biopsy), therapeutic, or complete lymphadenectomy. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. The TNM pathologic and clinical primary tumor classifications of Merkel cell carcinoma are the same. (from AJCC 7th Ed.)
Merkel Cell Carcinoma in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Merkel Cell Carcinoma with no evidence of primary tumor (e.g., nodal/metastatic presentation without associated primary). (from AJCC 7th Ed.)
Merkel cell carcinoma with a finding of in situ primary tumor. (from AJCC 7th Ed.)
Merkel cell carcinoma with less than or equal to 2 cm maximum tumor dimension. (from AJCC 7th Ed.)
Merkel cell carcinoma with greater than 2 cm but not more than 5 cm maximum tumor dimension. (from AJCC 7th Ed.)
A tympanometry test result indicating the lack of movement of the tympanic membrane due to middle ear pathology.
A tympanometry test result indicating the retraction of the tympanic membrane resulting from negative ear pressure.
Merkel cell carcinoma with over 5 cm maximum tumor dimension. (from AJCC 7th Ed.)
Merkel cell carcinoma with primary tumor invading bone, muscle, fascia, or cartilage. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. The TNM pathologic and clinical regional lymph nodes classifications of Merkel cell carcinoma are not the same. TNM pathologic regional lymph nodes findings are based on the histologic examination of the regional lymph nodes, following focused (sentinel lymph node biopsy), therapeutic, or complete lymphadenectomy. (from AJCC 7th Ed.)
Merkel cell carcinoma in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Merkel cell carcinoma with negative regional lymph nodes by pathologic examination. (from AJCC 7th Ed.)
Merkel cell carcinoma with metastasis in regional lymph node(s). (from AJCC 7th Ed.)
Merkel cell carcinoma with micrometastasis in regional lymph node(s). Micrometastases are diagnosed after sentinel or elective lymphadenectomy. (from AJCC 7th Ed.)
Merkel cell carcinoma with macrometastasis in regional lymph node(s). Macrometastases are defined as clinically detectable nodal metastases confirmed by therapeutic lymphadenectomy or needle biopsy. (from AJCC 7th Ed.)
Merkel cell carcinoma with in transit metastasis. In transit metastasis is defined as a tumor distinct from the primary lesion and located either (1) between the primary lesion and the draining regional lymph nodes or (2) distal to the primary lesion. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. (from AJCC 7th Ed.)
Merkel cell carcinoma with metastasis beyond regional lymph nodes. (from AJCC 7th Ed.)
Merkel cell carcinoma with metastasis to skin, subcutaneous tissues or distant lymph nodes. (from AJCC 7th Ed.)
Merkel cell carcinoma with metastasis to lung. (from AJCC 7th Ed.)
Merkel cell carcinoma with metastasis to all other visceral sites. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system. TNM clinical findings are based on clinical inspection and palpation of the involved area and the regional lymph nodes and/or radiologic studies. The TNM clinical and pathologic primary tumor classifications of Merkel cell carcinoma are the same. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. The TNM clinical and pathologic regional lymph nodes classifications of Merkel cell carcinoma are not the same. TNM clinical regional lymph nodes findings are based on clinical inspection and palpation of the regional lymph nodes and/or radiologic studies. (from AJCC 7th Ed.)
Merkel cell carcinoma with negative regional lymph nodes by clinical examination (inspection, palpation, and/or imaging). No pathologic node examination is performed. (from AJCC 7th Ed.)
Merkel cell carcinoma in transit metastasis. In transit metastasis is defined as a tumor distinct from the primary lesion and located either (1) between the primary lesion and the draining regional lymph nodes or (2) distal to the primary lesion. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. (from AJCC 7th Ed.)
Merkel cell carcinoma without distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of ophthalmic sites cancer, following the rules of the TNM AJCC v7 classification system.
A finding about one or more characteristics of carcinoma of the eyelid, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of carcinoma of the eyelid, following the rules of the TNM AJCC v7 classification system. The surgical nature of the histopathology specimen should be noted including incisional biopsy, excisional biopsy, wide local excision, radical excision including exenteration. The specimen should be carefully oriented and inked for margin evaluation. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the eyelid, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Carcinoma of the eyelid in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Carcinoma of the eyelid with no evidence of a primary tumor. (from AJCC 7th Ed.)
Carcinoma of the eyelid with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Carcinoma of the eyelid with tumor measuring 5 mm or less in greatest dimension and not invading the tarsal plate or eyelid margin. (from AJCC 7th Ed.)
Carcinoma of the eyelid with tumor measuring more than 5 mm, but not more than 10 mm in greatest dimension. Or, any tumor invading the tarsal plate or eyelid margin. (from AJCC 7th Ed.)
Carcinoma of the eyelid with tumor measuring more than 10 mm, but not more than 20 mm in greatest dimension. Or, tumor involving the full thickness of eyelid. (from AJCC 7th Ed.)
Carcinoma of the eyelid with tumor measuring more than 20 mm in greatest dimension. Or, any tumor invading adjacent ocular or orbital structures. Or, any T with perineural tumor invasion. (from AJCC 7th Ed.)
Carcinoma of the eyelid for which complete tumor resection requires enucleation, exenteration, or bone resection. (from AJCC 7th Ed.)
Unresectable carcinoma of the eyelid due to extensive invasion of ocular, orbital, and craniofacial structures, or brain. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the eyelid, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Carcinoma of the eyelid in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Carcinoma of the eyelid with no regional lymph node metastasis, based upon lymph node biopsy. (from AJCC 7th Ed.)
Carcinoma of the eyelid with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the eyelid, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for carcinoma of the eyelid. (from AJCC 7th Ed.)
Carcinoma of the eyelid with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of carcinoma of the eyelid, following the rules of the TNM AJCC v7 classification system. Staging of eyelid carcinoma begins with a comprehensive ophthalmic, orbital, and periorbital clinical examination. This approach includes a slit lamp or equivalent biomicroscopy evaluation, neuro-ophthalmic examination for evidence of perineural invasion, and regional assessment of the head and neck including lymphatic drainage basins. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of carcinoma of the eyelid, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Carcinoma of the eyelid with no regional lymph node metastasis, based upon clinical evaluation or imaging. (from AJCC 7th Ed.)
A monoclonal antibody against beta-amyloid (Abeta40/42) used in the treatment of Alzheimer's disease. Gantenerumab targets and binds to beta amyloid then is removed through effector cell-mediated clearance. This reduces the level of beta amyloid in the brain. In Alzheimer's disease, beta amyloid accumulates in the brain and is a key component in plaque formation.
A clinical finding about one or more characteristics of carcinoma of the eyelid, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Carcinoma of the eyelid without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of carcinoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system. No stage grouping is presently recommended for carcinoma of the conjunctiva. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system. Complete resection of the primary site is indicated (if possible). The specimen should be thoroughly sampled for histologic study of surgical margins, type of tumor, and grade of malignancy. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Carcinoma of the conjunctiva in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with no evidence of a primary tumor. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with tumor measuring 5 mm or less in greatest dimension. Note: tumors occur most commonly in the bulbar limbal conjunctiva. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with tumor measuring more than 5 mm in greatest dimension without invasion of adjacent structures. Adjacent structures include the cornea (3, 6, 9, or 12 clock hours), intraocular compartments, forniceal conjunctiva (lower and/or upper), palpebral conjunctiva (lower and/or upper), tarsal conjunctiva (lower and/or upper), lacrimal punctum and canaliculi (lower and/or upper), plica, caruncle, posterior eyelid lamella, anterior eyelid lamella, and/or eyelid margin (lower and/or upper). (from AJCC 7th Ed.)
An afucosylated, humanized monoclonal antibody against the alpha chain of the interleukin-5 receptor (IL-5Ra), with potential anti-asthmatic activity. Upon administration, benralizumab binds to IL-5Ra and elicits an antibody-directed cell cytotoxicity (ADCC) against IL-5Ra-expressing cells. This induces apoptosis in IL-5Ra-expressing cells and may reduce asthmatic episodes. IL-5Ra, expressed on both eosinophils and basophils, plays a key role in asthma.
Carcinoma of the conjunctiva with tumor invading adjacent structures (excluding the orbit). Adjacent structures include the cornea (3, 6, 9, or 12 clock hours), intraocular compartments, forniceal conjunctiva (lower and/or upper), palpebral conjunctiva (lower and/or upper), tarsal conjunctiva (lower and/or upper), lacrimal punctum and canaliculi (lower and/or upper), plica, caruncle, posterior eyelid lamella, anterior eyelid lamella, and/or eyelid margin (lower and/or upper). (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with tumor invading the orbit with or without further extension. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with tumor invading the orbital soft tissues, without bone invasion. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with tumor invading bone. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with tumor invading adjacent paranasal sinuses. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with tumor invading the brain. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Carcinoma of the conjunctiva in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with no regional lymph node metastasis. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for carcinoma of the conjunctiva. (from AJCC 7th Ed.)
Carcinoma of the conjunctiva with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of carcinoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system. The assessment of cancer is based on inspection, slit-lamp examination, and palpation of the regional lymph nodes. All conjunctival surfaces are inspected and photographed with eversion of the upper eyelid. High-frequency ultrasound (UBM) imaging should be performed when the tumor is found to be affixed to the globe and when intraocular invasion is suspected. Low-frequency ultrasound may also be used to evaluate the sclera, eye, and orbit. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of carcinoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Carcinoma of the conjunctiva without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system. No stage grouping is presently recommended for melanoma of the conjunctiva. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system. Complete resection of the primary site is indicated. Histopathologic evaluation for negative peripheral and deep margins should be performed. To best judge the depth of penetration of the tumor, sections should be made perpendicular to the epithelial surface. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Melanoma of the conjunctiva in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Melanoma of the conjunctiva with no evidence of a primary tumor. (from AJCC 7th Ed.)
Melanoma of the conjunctiva confined to the epithelium. (from AJCC 7th Ed.)
Melanoma of the bulbar conjunctiva with tumor measuring not more than 0.5 mm in thickness with invasion of the substantia propria. (from AJCC 7th Ed.)
Melanoma of the bulbar conjunctiva with tumor measuring more than 0.5 mm but not more than 1.5 mm in thickness with invasion of the substantia propria. (from AJCC 7th Ed.)
Melanoma of the bulbar conjunctiva with tumor measuring more than 1.5 mm in thickness with invasion of the substantia propria. (from AJCC 7th Ed.)
Melanoma of the palpebral, forniceal, or caruncular conjunctiva with tumor measuring not more than 0.5 mm in thickness with invasion of the substantia propria. (from AJCC 7th Ed.)
Melanoma of the palpebral, forniceal, or caruncular conjunctiva with tumor measuring more than 0.5 mm but not more than 1.5 mm in thickness with invasion of the substantia propria. (from AJCC 7th Ed.)
Melanoma of the palpebral, forniceal, or caruncular conjunctiva with tumor measuring more than 1.5 mm in thickness with invasion of the substantia propria. (from AJCC 7th Ed.)
Melanoma of the conjunctiva with tumor invading the eye, eyelid, nasolacrimal system, sinuses, or orbit. (from AJCC 7th Ed.)
Melanoma of the conjunctiva with tumor invading the central nervous system. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Melanoma of the conjunctiva in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Melanoma of the conjunctiva with no regional lymph node metastasis. (from AJCC 7th Ed.)
Melanoma of the conjunctiva with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for melanoma of the conjunctiva. (from AJCC 7th Ed.)
Melanoma of the conjunctiva with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system. The classification applies only to conjunctival melanoma and primary acquired melanosis with atypia. In general, there should be a histologic evaluation of the tumor. The clinical assessment of a melanocytic conjunctival tumor is based on inspection, slit-lamp examination, and palpation of the regional lymph nodes. All conjunctival surfaces should be inspected and photographed (including eversion of the upper eyelid). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
A humanized monoclonal antibody directed against the pancreatic cancer antigen MUC1, with potential antineoplastic activity. Clivatuzumab binds to tumor cells expressing the MUC1 antigen and prevents MUC1-mediated signaling. MUC1, a mucin antigen, is overexpressed in pancreatic cancer but not in normal, healthy pancreatic cells.
Melanoma confined to the conjunctival epithelium. (from AJCC 7th Ed.)
Melanoma of the bulbar conjunctiva less than or equal to 1 quadrant. Note: Quadrants are defined by clock hour, starting at the limbus (e.g., 6, 9, 12, 3) extending from the central cornea, to and beyond the eyelid margins. This will bisect the caruncle. (from AJCC 7th Ed.)
Melanoma of the bulbar conjunctiva more than 1 but less than or equal to 2 quadrants. (from AJCC 7th Ed.)
Melanoma of the bulbar conjunctiva more than 2 but less than or equal to 3 quadrants. (from AJCC 7th Ed.)
Melanoma of the bulbar conjunctiva greater than 3 quadrants. (from AJCC 7th Ed.)
Melanoma of the nonbulbar (palpebral, forniceal, but no caruncular) conjunctiva less than or equal to 1 quadrant. (from AJCC 7th Ed.)
Melanoma of the nonbulbar (palpebral, forniceal, but no caruncular) conjunctiva greater than 1 quadrant. (from AJCC 7th Ed.)
Any caruncular, less than or equal to 1 quadrant. (from AJCC 7th Ed.)
Any caruncular, greater than 1 quadrant. (from AJCC 7th Ed.)
Melanoma of the conjunctiva with local invasion. (from AJCC 7th Ed.)
Melanoma of the conjunctiva invading the globe. (from AJCC 7th Ed.)
Melanoma of the conjunctiva invading the eyelid. (from AJCC 7th Ed.)
Melanoma of the conjunctiva invading the orbit. (from AJCC 7th Ed.)
Melanoma of the conjunctiva invading a sinus. (from AJCC 7th Ed.)
Melanoma of the conjunctiva invading the central nervous system. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Melanoma of the conjunctiva with no regional lymph node metastasis; biopsy performed. (from AJCC 7th Ed.)
Melanoma of the conjunctiva with no regional lymph node metastasis; biopsy not performed. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of melanoma of the conjunctiva, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Melanoma of the conjunctiva without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of melanoma of the uvea, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of melanoma of the uvea, following the rules of the TNM AJCC v7 classification system. Resection of the primary tumor by iridectomy, iridocyclectomy, local resection, or enucleation is needed for complete pathologic staging. Assessment of the extent of the tumor, measured in clock hours of involvement, basal dimensions, tumor thickness, and margins of resection, is necessary. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of melanoma of the uvea, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of melanoma of the iris, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Melanoma of the iris in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Melanoma of the iris with no evidence of a primary tumor. (from AJCC 7th Ed.)
Melanoma of the iris with tumor limited to the iris. (from AJCC 7th Ed.)
Melanoma of the iris with tumor limited to the iris not more than 3 clock hours in size. (from AJCC 7th Ed.)
Melanoma of the iris with tumor limited to the iris more than 3 clock hours in size. (from AJCC 7th Ed.)
Melanoma of the iris with tumor limited to the iris with secondary glaucoma. (from AJCC 7th Ed.)
Melanoma of the iris with tumor confluent with or extending into the ciliary body, choroid, or both. (from AJCC 7th Ed.)
Melanoma of the iris with tumor confluent with or extending into the ciliary body, choroid, or both, with secondary glaucoma. (from AJCC 7th Ed.)
Melanoma of the iris with tumor confluent with or extending into the ciliary body, choroid, or both, with sclera extension. (from AJCC 7th Ed.)
Melanoma of the iris with tumor confluent with or extending into the ciliary body, choroid, or both, with sclera extension and secondary glaucoma. (from AJCC 7th Ed.)
Melanoma of the iris with extrascleral extension. (from AJCC 7th Ed.)
Melanoma of the iris with extrascleral extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Melanoma of the iris with extrascleral extension more than 5 mm in diameter. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of melanoma of the ciliary body and choroid, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Melanoma of the ciliary body and choroid in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Melanoma of the ciliary body and choroid with no evidence of a primary tumor. (from AJCC 7th Ed.)
Tumor size category 1. (from AJCC 7th Ed.)
Tumor size category 1 without ciliary body involvement and extraocular extension. (from AJCC 7th Ed.)
Tumor size category 1 with ciliary body involvement. (from AJCC 7th Ed.)
Tumor size category 1 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Tumor size category 1 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Tumor size category 2. (from AJCC 7th Ed.)
Tumor size category 2 without ciliary body involvement and extraocular extension. (from AJCC 7th Ed.)
Tumor size category 2 with ciliary body involvement. (from AJCC 7th Ed.)
Tumor size category 2 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Tumor size category 2 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Tumor size category 3. (from AJCC 7th Ed.)
Tumor size category 3 without ciliary body involvement and extraocular extension. (from AJCC 7th Ed.)
Tumor size category 3 with ciliary body involvement. (from AJCC 7th Ed.)
Tumor size category 3 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Tumor size category 3 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Tumor size category 4. (from AJCC 7th Ed.)
Tumor size category 4 without ciliary body involvement and extraocular extension. (from AJCC 7th Ed.)
Tumor size category 4 with ciliary body involvement. (from AJCC 7th Ed.)
Tumor size category 4 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Tumor size category 4 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter. (from AJCC 7th Ed.)
Any tumor size category with extraocular extension more than 5 mm in diameter. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of melanoma of the uvea, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Melanoma of the uvea in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Melanoma of the uvea with no regional lymph node metastasis. (from AJCC 7th Ed.)
Melanoma of the uvea with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of melanoma of the uvea, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for melanoma of the uvea. (from AJCC 7th Ed.)
Melanoma of the uvea with distant metastasis. (from AJCC 7th Ed.)
Melanoma of the uvea with distant metastasis, with the largest diameter of the largest metastasis measuring 3 cm or less. (from AJCC 7th Ed.)
Melanoma of the uvea with distant metastasis, with the largest diameter of the largest metastasis measuring 3.1-8.0 cm. (from AJCC 7th Ed.)
Melanoma of the uvea with distant metastasis, with the largest diameter of the largest metastasis measuring 8.0 cm or more. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of melanoma of the uvea, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of melanoma of the uvea, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Melanoma of the uvea in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
A finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Retinoblastoma in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Retinoblastoma with no evidence of a primary tumor. (from AJCC 7th Ed.)
Retinoblastoma with tumor confined to eye with no optic nerve or choroidal invasion. (from AJCC 7th Ed.)
Retinoblastoma with minimal optic nerve and/or choroidal invasion. (from AJCC 7th Ed.)
Retinoblastoma with tumor superficially invading optic nerve head but not extending past lamina cribrosa or tumor exhibiting focal choroidal invasion. (from AJCC 7th Ed.)
Retinoblastoma with tumor superficially invading optic nerve head but not extending past lamina cribrosa and exhibiting focal choroidal invasion. (from AJCC 7th Ed.)
Retinoblastoma with significant optic nerve and/or choroidal invasion. (from AJCC 7th Ed.)
Retinoblastoma with tumor invading optic nerve past lamina cribrosa but not to surgical resection line or tumor exhibiting massive choroidal invasion. (from AJCC 7th Ed.)
Retinoblastoma with tumor invading optic nerve past lamina cribrosa but not to surgical resection line and exhibiting massive choroidal invasion. (from AJCC 7th Ed.)
Retinoblastoma with tumor invading optic nerve to resection line or exhibiting extra-ocular extension elsewhere. (from AJCC 7th Ed.)
Retinoblastoma with tumor invading optic nerve to resection line but no extra-ocular extension is identified. (from AJCC 7th Ed.)
Retinoblastoma with tumor invading optic nerve to resection line and extra-ocular extension is identified. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Retinoblastoma in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Retinoblastoma with no regional lymph node involvement. (from AJCC 7th Ed.)
Retinoblastoma with regional lymph node involvement (preauricular, cervical). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for retinoblastoma. (from AJCC 7th Ed.)
Retinoblastoma with metastasis to sites other than CNS. (from AJCC 7th Ed.)
Discrete mass(es) without leptomeningeal and/or CSF involvement. (from AJCC 7th Ed.)
Leptomeningeal and/or CSF involvement. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system. All suspected cases of retinoblastoma should have a neural imaging scan. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Retinoblastoma with tumor no more than 2/3 the volume of the eye with no vitreous or subretinal seeding. (from AJCC 7th Ed.)
No tumor in either eye is greater than 3 mm in largest dimension or located closer than 1.5 mm to the optic nerve or fovea. (from AJCC 7th Ed.)
At least one tumor is greater than 3 mm in largest dimension or located closer than 1.5 mm to the optic nerve or fovea. No retinal detachment or subretinal fluid beyond 5 mm from the base of the tumor. (from AJCC 7th Ed.)
At least one tumor is greater than 3 mm in largest dimension or located closer than 1.5 mm to the optic nerve or fovea, with retinal detachment or subretinal fluid beyond 5 mm from the base of the tumor. (from AJCC 7th Ed.)
Tumors no more than 2/3 the volume of the eye with vitreous or subretinal seeding. Can have retinal detachment. (from AJCC 7th Ed.)
Focal vitreous and/or subretinal seeding of fine aggregates of tumor cells is present, but no large clumps or ""snowballs"" of tumor cells. (from AJCC 7th Ed.)
Massive vitreous and/or subretinal seeding is present, defined as diffuse clumps or ""snowballs"" of tumor cells. (from AJCC 7th Ed.)
Severe intraocular disease. (from AJCC 7th Ed.)
Tumor fills more than 2/3 of the eye. (from AJCC 7th Ed.)
One or more complications are present, which may include tumor-associated neovascular or angle closure glaucoma, tumor extension into the anterior segment, hyphema, vitreous hemorrhage, or orbital cellulitis. (from AJCC 7th Ed.)
Extraocular disease detected by imaging studies. (from AJCC 7th Ed.)
Invasion of the optic nerve. (from AJCC 7th Ed.)
Invasion into the orbit. (from AJCC 7th Ed.)
Intracranial extension not past chiasm. (from AJCC 7th Ed.)
Intracranial extension past chiasm. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Retinoblastoma with regional lymph node involvement (preauricular, cervical, submandibular). (from AJCC 7th Ed.)
Retinoblastoma with distal lymph node involvement. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Retinoblastoma with no metastasis. (from AJCC 7th Ed.)
Retinoblastoma with systemic metastasis. (from AJCC 7th Ed.)
Single lesion to sites other than CNS. (from AJCC 7th Ed.)
Multiple lesions to sites other than CNS. (from AJCC 7th Ed.)
Prechiasmatic CNS lesion(s). (from AJCC 7th Ed.)
Postchiasmatic CNS lesion(s). (from AJCC 7th Ed.)
A finding about one or more characteristics of carcinoma of the lacrimal gland, following the rules of the TNM AJCC v7 classification system. No stage grouping is presently recommended for carcinoma of the lacrimal gland. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the lacrimal gland, following the rules of the TNM AJCC v7 classification system. Complete resection of the mass is indicated. The specimen should be thoroughly sampled for evaluation of histologic type and grade of tumor, size, possible presence of a preexisting pleomorphic adenoma, and surgical margins (including the periosteum). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the lacrimal gland, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Carcinoma of the lacrimal gland in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with no evidence of a primary tumor. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with tumor measuring 2 cm or less in greatest dimension with or without extraglandular extension into the orbital soft tissue. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with tumor measuring more than 2 cm but not more than 4 cm in greatest dimension. Note: As the maximum size of the lacrimal gland is 2 cm, T2 and greater tumors will usually extend into the orbital soft tissue. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with tumor measuring more than 4 cm in greatest dimension. Note: As the maximum size of the lacrimal gland is 2 cm, T2 and greater tumors will usually extend into the orbital soft tissue. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with tumor invading periosteum or orbital bone or adjacent structures. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with tumor invading periosteum. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with tumor invading orbital bone. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with tumor invading adjacent structures (brain, sinus, pterygoid fossa, temporal fossa). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the lacrimal gland, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Carcinoma of the lacrimal gland in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with no regional lymph node metastasis. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of carcinoma of the lacrimal gland, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for carcinoma of the lacrimal gland. (from AJCC 7th Ed.)
Carcinoma of the lacrimal gland with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of carcinoma of the lacrimal gland, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of carcinoma of the lacrimal gland, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Carcinoma of the lacrimal gland without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of sarcoma of the orbit, following the rules of the TNM AJCC v7 classification system. No stage grouping is presently recommended for sarcoma of the orbit. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of sarcoma of the orbit, following the rules of the TNM AJCC v7 classification system. The nature of the histopathology specimen (fine-needle aspiration biopsy, excisional biopsy, lumpectomy, or total excision) should be noted. Pathologic classification is based on the specific histopathology of the tumor, its differentiation (grade), and the extent of removal (evaluation of the excisional margins). In total excision specimens, evaluation of the surgical margins is mandatory. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of sarcoma of the orbit, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Sarcoma of the orbit in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Sarcoma of the orbit with no evidence of a primary tumor. (from AJCC 7th Ed.)
Sarcoma of the orbit with tumor measuring 15 mm or less in greatest dimension. (from AJCC 7th Ed.)
Sarcoma of the orbit with tumor measuring more than 15 mm in greatest dimension without invasion of globe or bony wall. (from AJCC 7th Ed.)
Sarcoma of the orbit with tumor of any size with invasion of orbital tissues and/or bony walls. (from AJCC 7th Ed.)
Sarcoma of the orbit with tumor invasion of globe or periorbital structure, such as eyelids, temporal fossa, nasal cavity and paranasal sinuses, and/or central nervous system. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of sarcoma of the orbit, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Sarcoma of the orbit in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Sarcoma of the orbit with no regional lymph node metastasis. (from AJCC 7th Ed.)
Sarcoma of the orbit with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of sarcoma of the orbit, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for sarcoma of the orbit. (from AJCC 7th Ed.)
Sarcoma of the orbit with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of sarcoma of the orbit, following the rules of the TNM AJCC v7 classification system. Clinical classification should be based on the symptoms and signs related to loss of vision and visual field, degree of global displacement and loss of extraocular motility, and degree of compressive optic neuropathy. Diagnostic tests should include perimetry, ultrasonography, computed tomography, magnetic resonance imaging, and other imaging procedures when indicated. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of sarcoma of the orbit, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Sarcoma of the orbit without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v7 classification system. No stage grouping is presently recommended for ocular adnexal lymphoma. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Lymphoma extent is not specified. (from AJCC 7th Ed.)
No evidence of lymphoma. (from AJCC 7th Ed.)
Lymphoma involving the conjunctiva alone without orbital involvement. (from AJCC 7th Ed.)
Bulbar conjunctiva only. (from AJCC 7th Ed.)
Palpebral conjunctiva +/- fornix +/- caruncle. (from AJCC 7th Ed.)
Extensive conjunctival involvement. (from AJCC 7th Ed.)
Lymphoma with orbital involvement +/- any conjunctival involvement. (from AJCC 7th Ed.)
Anterior orbital involvement (+/- conjunctival involvement). (from AJCC 7th Ed.)
Anterior orbital involvement (+/- conjunctival involvement + lacrimal involvement). (from AJCC 7th Ed.)
Posterior orbital involvement (+/- conjunctival involvement +/- anterior involvement and +/- any extraocular muscle involvement). (from AJCC 7th Ed.)
Nasolacrimal drainage system involvement (+/- conjunctival involvement but not including nasopharynx). (from AJCC 7th Ed.)
Lymphoma with preseptal eyelid involvement +/- orbital involvement +/- any conjunctival involvement. Note: Preseptal tissues include dermis and orbicularis muscle of the anterior eyelid skin. (from AJCC 7th Ed.)
Orbital adnexal lymphoma extending beyond orbit to adjacent structures such as bone and brain. (from AJCC 7th Ed.)
Involvement of nasopharynx. (from AJCC 7th Ed.)
Osseous involvement (including periosteum). (from AJCC 7th Ed.)
Involvement of maxillofacial, ethmoidal, and/or frontal sinuses. (from AJCC 7th Ed.)
Intracranial spread. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Involvement of lymph nodes not assessed. (from AJCC 7th Ed.)
No evidence of lymph node involvement. (from AJCC 7th Ed.)
Involvement of ipsilateral regional lymph nodes. Note: The regional lymph nodes include preauricular (parotid), submandibular, and cervical. (from AJCC 7th Ed.)
Involvement of contralateral or bilateral regional lymph nodes. Note: The regional lymph nodes include preauricular (parotid), submandibular, and cervical. (from AJCC 7th Ed.)
Involvement of peripheral lymph nodes not draining ocular adnexal region. (from AJCC 7th Ed.)
Involvement of central lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for ocular adnexal lymphoma. (from AJCC 7th Ed.)
Noncontiguous involvement of tissues or organs external to the ocular adnexa (e.g., parotid gland, submandibular gland, lung, liver, spleen, kidney, breast, etc.). (from AJCC 7th Ed.)
Lymphomatous involvement of the bone marrow. (from AJCC 7th Ed.)
Both M1a and M1b involvement. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Ocular adnexal lymphoma with no evidence of involvement of other extranodal sites. (from AJCC 7th Ed.)
A finding about one or more characteristics of thoracic cancer, following the rules of the TNM AJCC v7 classification system. This classification is used for lung cancer and pleural mesothelioma. (from AJCC 7th Ed.)
A finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v7 classification system. This classification is used for both non-small cell and small cell lung carcinomas and for carcinoid tumors of the lung. Sarcomas and other rare tumors of the lung are not included. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v7 classification system. The pathologic classification uses the evidence acquired before treatment, supplemented or modified by the additional evidence acquired during and after surgery, particularly from pathologic examination. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Lung cancer with a tumor size of 3 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a. (from AJCC 7th Ed.)
Lung cancer with a tumor size of 2 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a. (from AJCC 7th Ed.)
Lung cancer with a tumor size more than 2 cm but 3 cm or less in greatest dimension, surrounded by lung or visceral pleura and without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). The uncommon superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified as T1a. (from AJCC 7th Ed.)
Lung cancer with a tumor size more than 3 cm but 7 cm or less or tumor with any of the following features (T2 tumors with these features are classified T2a if 5 cm or less): Involves main bronchus, 2 cm or more distal to the carina; Invades visceral pleura (PL1 or PL2); Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung. (from AJCC 7th Ed.)
Lung cancer with a tumor size more than 3 cm but 5 cm or less in greatest dimension. (from AJCC 7th Ed.)
Lung cancer with a tumor size more than 5 cm but 7 cm or less in greatest dimension. (from AJCC 7th Ed.)
Lung cancer with a tumor size more than 7 cm or one that directly invades any of the following: parietal pleural (PL3) chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumor in the main bronchus (less than 2 cm distal to the carina but without involvement of the carina); or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe. (from AJCC 7th Ed.)
Lung cancer with a tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodule(s) in a different ipsilateral lobe. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Lung cancer with metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary lymph nodes, including involvement by direct extension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for lung cancer. (from AJCC 7th Ed.)
Lung cancer with distant metastasis. (from AJCC 7th Ed.)
Lung cancer with separate tumor nodule(s) in a contralateral lobe; tumor with pleural nodules or malignant pleural (or pericardial) effusion. Most pleural (and pericardial) effusions with lung cancer are due to tumor. In a few patients, however, multiple cytopathologic examinations of pleural (or pericardial) fluid) are negative for tumor, and the fluid is nonbloody and is not an exudate. Where these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient should be classified as M0. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v7 classification system. The clinical classification is based on the evidence acquired before treatment, including physical examination, imaging studies, laboratory tests, and staging procedures such as bronchoscopy or esophagoscopy with ultrasound directed biopsies, mediastinoscopy, mediastinotomy, thoracentesis, and thoracoscopy as well as exploratory thoracotomy. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Lung cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of pleural mesothelioma, following the rules of the TNM AJCC v7 classification system. The staging system used in the AJCC 7th edition represents an adoption of the system proposed in 1995 by the International Mesothelioma Interest Group (IMIG), which was based on updated information about the relationship between tumor T and N status and overall survival. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of pleural mesothelioma, following the rules of the TNM AJCC v7 classification system. The pathologic staging is based on surgical resection. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of pleural mesothelioma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Pleural mesothelioma in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Pleural mesothelioma without evidence of primary tumor. (from AJCC 7th Ed.)
Pleural mesothelioma with a tumor limited to the ipsilateral parietal pleura with or without mediastinal pleura and with or without diaphragmatic pleural involvement. (from AJCC 7th Ed.)
Pleural mesothelioma with no involvement of the visceral pleura. (from AJCC 7th Ed.)
Pleural mesothelioma with a tumor also involving the visceral pleura. (from AJCC 7th Ed.)
Pleural mesothelioma with a tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following: involvement of diaphragmatic muscle; extension of tumor from visceral pleura into the underlying pulmonary parenchyma. (from AJCC 7th Ed.)
Pleural mesothelioma with a locally advanced but potentially respectable tumor. Tumor involving all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following: involvement of the endothoracic fascia; extension into the mediastinal fat; solitary, completely respectable focus of tumor extending into the soft tissues of the chest wall; nontransmural involvement of the pericardium. (from AJCC 7th Ed.)
Pleural mesothelioma with a locally advanced technically unresectable tumor. Tumor involving all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following: diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction; direct transdiaphragmatic extension of tumor to the peritoneum; direct extension of tumor to the contralateral pleura; direct extension of tumor to mediastinal organs; direct extension of tumor into the spine; tumor extending through to the internal surface of the pericardium with or without a pericardial effusion or tumor involving the myocardium. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of pleural mesothelioma, following the rules of the TNM classification system as they pertain to staging of regional lymph nodes.
Pleural mesothelioma in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Pleural mesothelioma with no regional lymph nodes metastases. (from AJCC 7th Ed.)
Pleural mesothelioma with metastases in the ipsilateral bronchopulmonary or hilar lymph nodes. (from AJCC 7th Ed.)
Pleural mesothelioma with metastases in the subcarinal or the ipsilateral mediastinal lymph nodes including the ipsilateral internal mammary and peridiaphragmatic nodes. (from AJCC 7th Ed.)
Pleural mesothelioma with metastases in the contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral supraclavicular lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of pleural mesothelioma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for pleural mesothelioma.
Pleural mesothelioma with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of pleural mesothelioma, following the rules of the TNM AJCC v7 classification system. The clinical staging depends on imaging most frequently computed tomography (CT) and more recently FDG positron emission tomography (FDG-PET) scanning. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of pleural mesothelioma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Pleural mesothelioma without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of head and neck cancer, following the rules of the TNM AJCC v7 classification system.
A finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v7 classification system. Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging is determined after the complete resection of the primary site and/or regional nodal dissection, followed by pathologic examination of the resected specimen(s). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Lip and oral cavity cancer with moderately advanced local disease. Lip: Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose. Oral cavity: Tumor invades adjacent structures only (e.g., through cortical bone [mandible or maxilla] into deep [extrinsic] muscle of tongue [genioglossus, hyoglossus, palatoglossus, and styloglossus], maxillary sinus, skin of face). (from AJCC 7th Ed.)
Lip and oral cavity cancer with very advanced local disease. Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Lip and oral cavity cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for lip and oral cavity cancer.
A clinical finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v7 classification system. The assessment of the primary tumor is based on inspection and palpation of the oral cavity and neck. Additional studies may include CT, MRI, or ultrasound. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Lip and oral cavity cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Lip and oral cavity cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of pharyngeal cancer, following the rules of the TNM AJCC v7 classification system. Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included in this classification. (from AJCC 7th Ed.)
A finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in clinical staging and in histologic study of the surgically resected specimens. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Nasopharyngeal cancer with tumor confined to the nasopharynx, or tumor extending to oropharynx and/or nasal cavity without parapharyngeal extension. Parapharyngeal extension denotes posterolateral infiltration of tumor. (from AJCC 7th Ed.)
Nasopharyngeal cancer with parapharyngeal extension. Parapharyngeal extension denotes posterolateral infiltration of tumor. (from AJCC 7th Ed.)
Nasopharyngeal cancer with tumor involving bony structures of skull base and/or paranasal sinuses. (from AJCC 7th Ed.)
Nasopharyngeal cancer with intracranial extension and/or involvement of cranial nerves, hypopharynx, orbit, or with extension to the infratemporal fossa/masticator space. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. The distribution and the prognostic impact of regional lymph node spread from nasopharynx cancer, particularly of the undifferentiated type, are different from those of other head and neck mucosal cancers and justify the use of a different N classification scheme. (from AJCC 7th Ed.)
Nasopharyngeal cancer with unilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa, and/or unilateral or bilateral, retropharyngeal lymph nodes, 6 cm or less in greatest dimension. Midline nodes are considered ipsilateral nodes. (from AJCC 7th Ed.)
Nasopharyngeal cancer with bilateral metastasis in cervical lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa. Midline nodes are considered ipsilateral nodes. (from AJCC 7th Ed.)
Nasopharyngeal cancer with metastasis in a lymph node (s) more than 6 cm in greatest dimension and/or to supraclavicular fossa. Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described by Ho. It is defined by three points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, (3) the point where the neck meets the shoulder. This would include caudal portions of levels IV and VB. All cases with lymph nodes (whole or part) in the fossa are considered N3b. (from AJCC 7th Ed.)
Nasopharyngeal cancer with extension to the supraclavicular fossa. Supraclavicular zone or fossa is relevant to the staging of nasopharyngeal carcinoma and is the triangular region originally described by Ho. It is defined by three points: (1) the superior margin of the sternal end of the clavicle, (2) the superior margin of the lateral end of the clavicle, (3) the point where the neck meets the shoulder. This would include caudal portions of levels IV and VB. All cases with lymph nodes (whole or part) in the fossa are considered N3b. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for nasopharyngeal cancer.
A clinical finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v7 classification system. The assessment is based primarily on inspection and on indirect and direct endoscopy. Palpation of sites (when feasible) and of neck nodes is essential. Neurologic evaluation of all cranial nerves is required. Imaging studies are essential in clinical staging of pharynx tumors. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Nasopharyngeal cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Nasopharyngeal cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in clinical staging and in histologic study of the surgically resected specimens. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Oropharyngeal cancer with tumor size more than 4 centimeters in greatest dimension or extension to lingual surface of epiglottis. (from AJCC 7th Ed.)
Oropharyngeal cancer with moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of larynx. (from AJCC 7th Ed.)
Oropharyngeal cancer with very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Metastases at level VII are considered regional lymph node metastases. (from AJCC 7th Ed.)
Oropharyngeal cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
Oropharyngeal cancer with metastasis in a lymph node more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for oropharyngeal cancer.
A clinical finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of oropharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Oropharyngeal cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Oropharyngeal cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in clinical staging and in histologic study of the surgically resected specimens. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Hypopharyngeal cancer with tumor limited to one subsite of hypopharynx and/or 2 cm or less in greatest dimension. (from AJCC 7th Ed.)
Hypopharyngeal cancer with tumor measuring more than 4 cm in greatest dimension or with fixation of hemilarynx or extension to esophagus. (from AJCC 7th Ed.)
Hypopharyngeal cancer with moderately advanced local disease. Tumor invades the thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue. Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. (from AJCC 7th Ed.)
Hypopharyngeal cancer with very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Metastases at level VII are considered regional lymph node metastases. (from AJCC 7th Ed.)
Hypopharyngeal cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
Hypopharyngeal cancer with metastasis in a lymph node more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for hypopharyngeal cancer.
A clinical finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Hypopharyngeal cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Hypopharyngeal cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v7 classification system. Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included in this classification. (from AJCC 7th Ed.)
A finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in clinical staging and in histologic study of the surgically resected specimens. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Supraglottic cancer with tumor limited to larynx with vocal cord fixation and/or invading any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage. (from AJCC 7th Ed.)
Supraglottic cancer with moderately advanced local disease. Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 7th Ed.)
Supraglottic cancer with very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Metastases at level VII are considered regional lymph node metastases. (from AJCC 7th Ed.)
Supraglottic cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for supraglottic cancer.
A clinical finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v7 classification system. The assessment is accomplished primarily by inspection, using indirect mirror and direct endoscopic examination with a fiberoptic nasolaryngoscope. The tumor must be confirmed histologically, and any other data obtained by biopsies may be included. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Supraglottic cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Supraglottic cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in clinical staging and in histologic study of the surgically resected specimens. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Glottic cancer with tumor limited to the larynx with vocal cord fixation and /or invasion of paraglottic space, and/or inner cortex of the thyroid cartilage. (from AJCC 7th Ed.)
Glottic cancer with moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 7th Ed.)
Glottic cancer with very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Metastases at level VII are considered regional lymph node metastases. (from AJCC 7th Ed.)
Glottic cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for glottic cancer.
A clinical finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v7 classification system. The assessment is accomplished primarily by inspection, using indirect mirror and direct endoscopic examination with a fiberoptic nasolaryngoscope. The tumor must be confirmed histologically, and any other data obtained by biopsies may be included. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Glottic cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Glottic cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in clinical staging and in histologic study of the surgically resected specimens. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Subglottic cancer with moderately advanced local disease. Tumor invades cricoid or thyroid cartilage and/or invades tissues behind the larynx (e.g. trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 7th Ed.)
Subglottic cancer with very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Metastases at level VII are considered regional lymph node metastases. (from AJCC 7th Ed.)
Subglottic cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for subglottic cancer.
A clinical finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v7 classification system. The assessment is accomplished primarily by inspection, using indirect mirror and direct endoscopic examination with a fiberoptic nasolaryngoscope. The tumor must be confirmed histologically, and any other data obtained by biopsies may be included. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Subglottic cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Subglottic cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of nasal cavity and paranasal sinus cancer, following the rules of the TNM AJCC v7 classification system. Nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included in this classification. (from AJCC 7th Ed.)
A finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in clinical staging and in histologic study of the surgically resected specimens. The surgeon's evaluation of gross unresected residual tumor must also be included. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Maxillary sinus cancer with moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. (from AJCC 7th Ed.)
Maxillary sinus cancer with very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve, nasopharynx, or clivus. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Maxillary sinus cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for maxillary sinus cancer.
A clinical finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v7 classification system. The assessment is based on inspection and palpation, including examination of the orbits, nasal and oral cavities, and nasopharynx, and neurologic examination of the cranial nerves. Nasal endoscopy with rigid or fiberoptic flexible instruments is recommended. Radiologic assessment with magnetic resonance imaging (MRI) or computed tomography (CT) is mandatory for accurate pretreatment staging of malignant tumors of the sinuses. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Maxillary sinus cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Maxillary sinus cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in clinical staging and in histologic study of the surgically resected specimens. The surgeon's evaluation of gross unresected residual tumor must also be included. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Nasal cavity and ethmoid sinus cancer with moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. (from AJCC 7th Ed.)
Nasal cavity and ethmoid sinus cancer with very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve, nasopharynx, or clivus. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Nasal cavity and ethmoid sinus cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for nasal cavity and ethmoid sinus cancer.
A clinical finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v7 classification system. The assessment is based on inspection and palpation, including examination of the orbits, nasal and oral cavities, and nasopharynx, and neurologic examination of the cranial nerves. Nasal endoscopy with rigid or fiberoptic flexible instruments is recommended. Radiologic assessment with magnetic resonance imaging (MRI) or computed tomography (CT) is mandatory for accurate pretreatment staging of malignant tumors of the sinuses. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Nasal cavity and ethmoid sinus cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Nasal cavity and ethmoid sinus cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v7 classification system. This classification applies to parotid, submandibular, and sublingual glands. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Major salivary gland cancer with moderately advanced disease. Tumor invades skin, mandible, ear canal, and/or facial nerve. (from AJCC 7th Ed.)
Major salivary gland cancer with very advanced disease. Tumor invades skull base and/or pterygoid plates and/or encases carotid artery. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for major salivary gland cancer.
A clinical finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v7 classification system. The assessment of primary salivary gland tumors includes a pertinent history, (pain, trismus, etc.), inspection, palpation, and evaluation of the cranial nerves. Radiologic studies may add information valuable for staging. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Major salivary gland cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Major salivary gland cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Mucosal melanoma of the head and neck with mucosal disease. (from AJCC 7th Ed.)
Mucosal melanoma of the head and neck with moderately advanced disease. Tumor involves deep soft tissue, cartilage, bone, or overlying skin. (from AJCC 7th Ed.)
Mucosal melanoma of the head and neck with very advanced disease. Tumor involves brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space, or mediastinal structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Mucosal melanoma of the head and neck in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Mucosal melanoma of the head and neck with no metastases to regional lymph nodes. (from AJCC 7th Ed.)
Mucosal melanoma of the head and neck with regional lymph node metastases. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for mucosal melanoma of the head and neck.
Mucosal melanoma of the head and neck with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Mucosal melanoma of the head and neck without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v7 classification system. Both the histologic diagnosis and the age of the patient are of such importance in the behavior and prognosis of thyroid cancer that these factors are included in this staging system. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging requires the use of all information obtained in the clinical staging, as well as histologic study of the surgically resected specimens. The surgeon's description of gross unresected residual tumor must also be included. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. Note: All categories may be subdivided: (s) solitary tumors and (m) multifocal tumor (the largest determines the classification) (from AJCC 7th Ed.)
Thyroid cancer with a tumor size of 1 cm or less in greatest dimension, limited to the thyroid gland. (from AJCC 7th Ed.)
Thyroid cancer with a tumor size of more than 1 cm but not more than 2 cm in greatest dimension, limited to the thyroid gland. (from AJCC 7th Ed.)
Thyroid cancer with moderately advanced local disease. Tumor of any size extending beyond the thyroid gland capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve. (from AJCC 7th Ed.)
Intrathyroidal anaplastic carcinoma. (from AJCC 7th Ed.)
Thyroid cancer with very advanced disease. Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels. (from AJCC 7th Ed.)
Anaplastic carcinoma with gross extrathyroid extension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Thyroid cancer with metastasis to unilateral, bilateral or contralateral cervical (Levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (Level VII). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for thyroid cancer.
A clinical finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v7 classification system. The assessment of a thyroid tumor depends on inspection and palpation of the thyroid gland and regional lymph nodes. Indirect laryngoscopy to evaluate vocal cord motion is essential. A variety of imaging procedures can provide additional useful information. These include radioisotope thyroid scans, ultrasonography, computed tomography scans (CT), magnetic resonance imaging (MRI) scans, and PET scans. The diagnosis of thyroid cancer must be confirmed by needle biopsy or open biopsy of the tumor. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of thyroid cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Thyroid cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Thyroid cancer with distant metastasis. (from AJCC 7th Ed.)
A rare disorder of infancy characterized by marked reduction or absence of megakaryocytes and thrombocytopenia.
A finding about one or more characteristics of genitourinary system cancer, following the rules of the TNM AJCC v7 classification system.
A finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v7 classification system. Primary urethral carcinomas and melanomas are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v7 classification system. Complete resection of the primary site with appropriate margins is required for pathologic classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Penile cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Penile cancer with no evidence of a primary tumor. (from AJCC 7th Ed.)
Penile cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Penile cancer with a finding of noninvasive verrucous carcinoma. Note: Broad pushing penetration (invasion) is permitted; destructive invasion is against this diagnosis. (from AJCC 7th Ed.)
Penile cancer with tumor invading subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3-4), or tumor invading subepithelial connective tissue with lymph vascular invasion or is poorly differentiated. (from AJCC 7th Ed.)
Penile cancer with tumor invading subepithelial connective tissue without lymph vascular invasion and is not poorly differentiated (i.e., grade 3-4). (from AJCC 7th Ed.)
Penile cancer with tumor invading subepithelial connective tissue with lymph vascular invasion or is poorly differentiated. (from AJCC 7th Ed.)
Penile cancer with tumor invading corpus spongiosum or cavernosum. (from AJCC 7th Ed.)
Penile cancer with tumor invading urethra. (from AJCC 7th Ed.)
Penile cancer with tumor invading other adjacent structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Pathologic stage definitions are based on biopsy or surgical excision findings. (from AJCC 7th Ed.)
Penile cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Penile cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Penile cancer with metastasis in a single inguinal lymph node. (from AJCC 7th Ed.)
Penile cancer with metastasis in multiple or bilateral inguinal lymph nodes. (from AJCC 7th Ed.)
Penile cancer with extranodal extension of lymph node metastasis or pelvic lymph node(s) unilateral or bilateral. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for penile cancer. (from AJCC 7th Ed.)
Penile cancer with distant metastasis (lymph node metastasis outside of the true pelvis in addition to visceral or bone sites). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Clinical stage definitions are based on palpation and imaging. (from AJCC 7th Ed.)
Penile cancer with no palpable or visibly enlarged inguinal lymph nodes. (from AJCC 7th Ed.)
Penile cancer with palpable mobile unilateral inguinal lymph node. (from AJCC 7th Ed.)
Penile cancer with palpable mobile multiple or bilateral inguinal lymph nodes. (from AJCC 7th Ed.)
Penile cancer with palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Penile cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system. Sarcomas and transitional cell carcinomas are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. There is no pathologic T1 classification for prostate cancer. (from AJCC 7th Ed.)
Prostate cancer with extraprostatic extension or microscopic invasion of bladder neck. Positive surgical margin should be indicated by an R1 descriptor (residual microscopic disease). (from AJCC 7th Ed.)
Prostate cancer with tumor invading the rectum, levator muscles, and/or pelvic wall. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for prostate cancer. When more than one site of metastasis is present, the most advanced category is used. pM1c is most advanced. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. (from AJCC 7th Ed.)
No evidence of primary tumor. (from AJCC 7th Ed.)
Clinically inapparent tumor neither palpable nor visible by imaging. (from AJCC 7th Ed.)
Tumor incidental histologic finding in 5% or less of tissue resected. (from AJCC 7th Ed.)
Tumor incidental histologic finding in more than 5% of tissue resected. (from AJCC 7th Ed.)
Tumor identified by needle biopsy (e.g., because of elevated PSA). (from AJCC 7th Ed.)
Prostate cancer confined within the prostate. Tumor found in one or both lobes by needle biopsy, but not palpable or reliably visible by imaging, is classified as T1c. (from AJCC 7th Ed.)
Prostate cancer with tumor involving one-half of one lobe or less. (from AJCC 7th Ed.)
Prostate cancer with tumor involving more than one-half of one lobe, but not both lobes. (from AJCC 7th Ed.)
Prostate cancer with tumor involving both lobes. (from AJCC 7th Ed.)
Prostate cancer extending through the prostatic capsule. Invasion into the prostatic apex or into (but not beyond) the prostatic capsule is classified not as T3 but as T2. (from AJCC 7th Ed.)
Prostate cancer with extracapsular extension (unilateral or bilateral). (from AJCC 7th Ed.)
Prostate cancer invading seminal vesicle(s). (from AJCC 7th Ed.)
Prostate cancer with fixed tumor or tumor invading adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. (from AJCC 7th Ed.)
Prostate cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Prostate cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Prostate cancer with metastasis in regional lymph node(s). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Prostate cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Prostate cancer with distant metastasis. (from AJCC 7th Ed.)
Prostate cancer with metastasis to non-regional lymph node(s). (from AJCC 7th Ed.)
Prostate cancer with metastasis to bone(s). (from AJCC 7th Ed.)
Prostate cancer with metastasis to other site(s) with or without bone disease. (from AJCC 7th Ed.)
A finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v7 classification system. Histologic examination of the orchiectomy specimen must be used for the pathologic examination. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. The extent of primary tumor is usually classified after radical orchiectomy, and for this reason, a pathologic stage is assigned. (from AJCC 7th Ed.)
Testicular cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
No evidence of primary tumor (e.g., histologic scar in testis). (from AJCC 7th Ed.)
Intratubular germ cell neoplasia (carcinoma in situ). (from AJCC 7th Ed.)
Testicular cancer with tumor limited to the testis and epididymis without vascular/lymphatic invasion; tumor may invade into the tunica albuginea but not the tunica vaginalis. (from AJCC 7th Ed.)
Testicular cancer with tumor limited to the testis and epididymis with vascular/lymphatic invasion, or tumor extending through the tunica albuginea with involvement of the tunica vaginalis. (from AJCC 7th Ed.)
Testicular cancer with tumor invading the spermatic cord with or without vascular/lymphatic invasion. (from AJCC 7th Ed.)
Testicular cancer with tumor invading the scrotum with or without vascular/lymphatic invasion. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. (from AJCC 7th Ed.)
Testicular cancer in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Testicular cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Metastasis with a lymph node mass 2 cm or less in greatest dimension and less than or equal to five nodes positive, none more than 2 cm in greatest dimension. (from AJCC 7th Ed.)
Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or more than five nodes positive, none more than 5 cm; or evidence of extranodal extension of tumor. (from AJCC 7th Ed.)
Metastasis with a lymph node mass more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for testicular cancer. (from AJCC 7th Ed.)
Testicular cancer with distant metastasis. (from AJCC 7th Ed.)
Testicular cancer with non-regional nodal or pulmonary metastasis. (from AJCC 7th Ed.)
Testicular cancer with metastasis other than to non-regional lymph nodes and lung. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. (from AJCC 7th Ed.)
Testicular cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Metastasis with a lymph node mass 2 cm or less in greatest dimension; or multiple lymph nodes, none more than 2 cm in greatest dimension. (from AJCC 7th Ed.)
Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, any one mass greater than 2 cm but not more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Testicular cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Testicular cancer with distant metastasis other than to non-regional lymph nodes and lung. (from AJCC 7th Ed.)
A finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v7 classification system. Renal pelvis and ureter cancers are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v7 classification system. Histologic examination of the surgical specimen and confirmation of the disease extent is required. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. (from AJCC 7th Ed.)
Kidney cancer with tumor more than 7 cm but less than or equal to 10 cm in greatest dimension, limited to the kidney. (from AJCC 7th Ed.)
Kidney cancer with tumor more than 10 cm in greatest dimension, limited to the kidney. (from AJCC 7th Ed.)
Kidney cancer with tumor extending into major veins or perinephric tissues but not into the ipsilateral adrenal gland and not beyond Gerota's fascia. (from AJCC 7th Ed.)
Kidney cancer with tumor grossly extending into the renal vein or its segmental (muscle containing) branches or tumor invading perirenal and/or renal sinus fat but not beyond Gerota's fascia. (from AJCC 7th Ed.)
Kidney cancer with tumor grossly extending into the vena cava below the diaphragm. (from AJCC 7th Ed.)
Kidney cancer with tumor grossly extending into the vena cava above the diaphragm, or invading the wall of the vena cava. (from AJCC 7th Ed.)
Kidney cancer with tumor invading beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. (from AJCC 7th Ed.)
Kidney cancer with metastasis in regional lymph node(s). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for kidney cancer. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v7 classification system. Clinical examination, abdominal computed tomography scanning, and other appropriate imaging techniques are required for assessment of the primary tumor and its extensions, both local and distant. Evaluation for distant metastasis should be done by laboratory biochemical studies, chest radiographs, and, if clinically indicated, additional studies. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Kidney cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Kidney cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v7 classification system. Pathologic staging depends on histologic determination of the extent of invasion by the primary tumor. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Renal pelvis and ureter cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with no evidence of a primary tumor. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with a finding of papillary noninvasive carcinoma. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with tumor invading subepithelial connective tissue. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with tumor invading the muscularis. (from AJCC 7th Ed.)
For renal pelvis cancer only: tumor invading beyond muscularis into peripelvic fat or the renal parenchyma. For ureter cancer only: tumor invading beyond muscularis into periureteric fat. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with tumor invading adjacent organs, or through the kidney into the perinephric fat. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Note: laterality does not affect the N classification. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with metastasis in a single lymph node, 2 cm or less in greatest dimension. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with metastasis in a single lymph node, more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, none more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with metastasis in a lymph node, more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for renal pelvis and ureter cancer. (from AJCC 7th Ed.)
Renal pelvis and ureter cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v7 classification system. Primary tumor assessment includes radiographic imaging, usually by intravenous and/or retrograde pyelography. Computerized tomography scanning can be used to assess regional nodes. Ureteroscopic visualization of the tumor is desirable, and tissue biopsy through the ureteroscope may be performed if feasible. Urine cytology may help determine tumor grade if tissue is not available. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Renal pelvis and ureter cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v7 classification system. Pathologic staging is based on the histologic review of the radical or partial cystectomy specimen. Microscopic examination and confirmation of extent of disease are required. Laterality does not affect the N classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Bladder cancer with tumor invading the muscularis propria. (from AJCC 7th Ed.)
Bladder cancer with tumor invading the superficial muscularis propria (inner half). (from AJCC 7th Ed.)
Bladder cancer with tumor invading the deep muscularis propria (outer half). (from AJCC 7th Ed.)
Bladder cancer with tumor invading any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall. (from AJCC 7th Ed.)
Bladder cancer with tumor invading prostatic stroma, uterus, vagina. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. Note: regional lymph nodes include both primary and secondary drainage regions. All other nodes above the aortic bifurcation are considered distant lymph nodes. (from AJCC 7th Ed.)
Bladder cancer with single regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node). (from AJCC 7th Ed.)
Bladder cancer with multiple regional lymph node metastases in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node metastasis). (from AJCC 7th Ed.)
Bladder cancer with metastasis to the common iliac lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for bladder cancer. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v7 classification system. Primary tumor assessment includes bimanual examination under anesthesia before and after endoscopic surgery (biopsy or transurethral resection) and histologic verification of the presence or absence of tumor when indicated. Appropriate imaging techniques for extravesical extension of the primary tumor and lymph node evaluation should be incorporated into clinical staging. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Bladder cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Bladder cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Urethral cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Urethral cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Urethral cancer with a finding of noninvasive papillary, polypoid, or verrucous carcinoma. (from AJCC 7th Ed.)
Urethral cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Urethral cancer with tumor invading subepithelial connective tissue. (from AJCC 7th Ed.)
Urethral cancer with tumor invading any of the following: corpus spongiosum, prostate, periurethral muscle. (from AJCC 7th Ed.)
Urethral cancer with tumor invading any of the following: corpus cavernosum, beyond prostatic capsule, anterior vagina, bladder neck. (from AJCC 7th Ed.)
Urethral cancer with tumor invading other adjacent organs. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of urothelial (transitional cell) carcinoma of the prostate, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Urothelial (transitional cell) carcinoma of the prostate with a finding of carcinoma in situ and involvement of the prostatic urethra. (from AJCC 7th Ed.)
Urothelial (transitional cell) carcinoma of the prostate with a finding of carcinoma in situ and involvement of the prostatic ducts. (from AJCC 7th Ed.)
Urothelial (transitional cell) carcinoma of the prostate with tumor invading urethral subepithelial connective tissue. (from AJCC 7th Ed.)
Urothelial (transitional cell) carcinoma of the prostate with tumor invading any of the following: prostatic stroma, corpus spongiosum, periurethral muscle. (from AJCC 7th Ed.)
Urothelial (transitional cell) carcinoma of the prostate with tumor invading any of the following: corpus cavernosum, beyond prostatic capsule, bladder neck (extraprostatic extension). (from AJCC 7th Ed.)
Urothelial (transitional cell) carcinoma of the prostate with tumor invading other adjacent organs (invasion of the bladder). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Urethral cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Urethral cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Urethral cancer with metastasis in a singe lymph node 2 cm or less in greatest dimension. (from AJCC 7th Ed.)
Urethral cancer with metastasis in a singe lymph node more than 2 cm in greatest dimension or in multiple lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for urethral cancer. (from AJCC 7th Ed.)
Urethral cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Urethral cancer in which there is no evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of adrenal cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of adrenal cancer, following the rules of the TNM AJCC v7 classification system. Resection of the primary tumor and examination for lymph node involvement and extent of disease (including vascular invasion) should be performed. Tumor size and weight should be recorded accurately in every case. Histologic examination and confirmation of extent of disease are required. Disease free and overall survival rates appear to correlate strongly with stage of adrenal cortical carcinoma. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of adrenal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Adrenal cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Adrenal cancer with no evidence of a primary tumor. (from AJCC 7th Ed.)
Adrenal cancer with tumor measuring 5 cm or less in greatest dimension, without extra-adrenal invasion. (from AJCC 7th Ed.)
Adrenal cancer with tumor measuring more than 5 cm in greatest dimension without extra-adrenal invasion. (from AJCC 7th Ed.)
Adrenal cancer with tumor of any size with local invasion, without invasion of adjacent organs. Adjacent organs include kidney, diaphragm, great vessels, pancreas, spleen, and liver. (from AJCC 7th Ed.)
Adrenal cancer with tumor of any size, with invasion of adjacent organs. Adjacent organs include kidney, diaphragm, great vessels, pancreas, spleen, and liver. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of adrenal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Adrenal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Adrenal cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Adrenal cancer with metastasis in regional lymph node(s). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of adrenal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for adrenal cancer. (from AJCC 7th Ed.)
Adrenal cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of adrenal cancer, following the rules of the TNM AJCC v7 classification system. Clinical examination and radiographic imaging are required to assess the size of the primary tumor and the extent of disease, both local and distant. Biochemical studies should be performed to evaluate the functional status of the tumor. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of adrenal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Adrenal cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of female reproductive system cancer, following the rules of the TNM AJCC v7 classification system.
A finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v7 classification system. Vulvar cancer is a surgically staged malignancy. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Vulvar cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Vulvar cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Vulvar cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Invasive vulvar cancer confined to the vulva or perineum. (from AJCC 7th Ed.)
Vulvar cancer with tumor size 2 cm or less, confined to the vulva or perineum and with stromal invasion 1.0 mm or less. The depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. (from AJCC 7th Ed.)
Vulvar cancer with tumor size greater than 2 cm, or any size with stromal invasion more than 1.0 mm, confined to the vulva or perineum. (from AJCC 7th Ed.)
Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement). (from AJCC 7th Ed.)
Vulvar cancer with tumor of any size with extension to any of the following: upper/proximal 2/3 urethra, upper/proximal 2/3 vagina, bladder mucosa, rectal mucosa, or fixed to pelvic bone. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Vulvar cancer in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Vulvar cancer without regional lymph node metastasis. (from AJCC 7th Ed.)
Vulvar cancer with one or two lymph node metastasis each measuring 5 mm or less, or one lymph node metastasis measuring 5 mm or greater. (from AJCC 7th Ed.)
Vulvar cancer with one or two lymph node metastasis each measuring 5 mm or less. (from AJCC 7th Ed.)
Vulvar cancer with one lymph node metastasis measuring 5 mm or greater. (from AJCC 7th Ed.)
Vulvar cancer with three or more lymph node metastases each measuring 5 mm or less, or two or more lymph node metastases measuring 5 mm or greater, or lymph node metastasis with extracapsular spread. (from AJCC 7th Ed.)
Vulvar cancer with three or more lymph node metastases each measuring 5 mm or less. (from AJCC 7th Ed.)
Vulvar cancer with two or more lymph node metastases measuring 5 mm or greater. (from AJCC 7th Ed.)
Vulvar cancer with lymph node metastasis with extracapsular spread. (from AJCC 7th Ed.)
Vulvar cancer with fixed or ulcerated regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for vulvar cancer.
Vulvar cancer with distant metastasis (including pelvic lymph node metastasis). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Vulvar cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Vaginal cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Vaginal cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Vaginal cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Vaginal cancer with a tumor confined to vagina. (from AJCC 7th Ed.)
Vaginal cancer invading the paravaginal tissues but not the pelvic wall. (from AJCC 7th Ed.)
Vaginal cancer extending to the pelvic wall. Pelvic wall is defined as muscle, fascia, neurovascular structures, or skeletal portions of the bony pelvis. (from AJCC 7th Ed.)
Vaginal cancer invading the mucosa of the bladder or rectum and/or extending beyond the true pelvis (bullous edema is not sufficient evidence to classify a tumor as T4). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Vaginal cancer in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Vaginal cancer without regional lymph node metastasis. (from AJCC 7th Ed.)
Vaginal cancer with pelvic or inguinal lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for vaginal cancer.
Vaginal cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Vaginal cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system. Because many patients are treated by radiation and never undergo surgical-pathologic staging, clinical staging provides uniformity and is preferred. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Cervical cancer in which primary tumor cannot be assessed. (from AJCC 7th Ed.)
Cervical cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Cervical cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Cervical cancer confined to uterus (extension to corpus should be disregarded). (from AJCC 7th Ed.)
Cervical cancer with clinically visible lesion confined to the cervix. (from AJCC 7th Ed.)
Cervical cancer with clinically visible lesion 4.0 cm or less in greatest dimension confined to the cervix. (from AJCC 7th Ed.)
Invasive cervical cancer with clinically visible lesion more than 4.0 cm in greatest dimension confined to the cervix. (from AJCC 7th Ed.)
Cervical cancer invades beyond uterus but not to pelvic wall or to lower third of vagina. (from AJCC 7th Ed.)
Cervical cancer invades beyond uterus but not to pelvic wall or to lower third of vagina. There is no parametrial invasion. (from AJCC 7th Ed.)
Cervical cancer invades beyond uterus but not to pelvic wall or to lower third of vagina. There is no parametrial invasion. Clinically visible lesions 4.0 cm or less in greatest dimension are present. (from AJCC 7th Ed.)
Cervical cancer invades beyond uterus but not to pelvic wall or to lower third of vagina. There is no parametrial invasion. Clinically visible lesions more than 4.0 cm in greatest dimension are present. (from AJCC 7th Ed.)
Cervical cancer invades beyond uterus but not to pelvic wall or to lower third of vagina. Parametrial invasion is present. (from AJCC 7th Ed.)
Cervical cancer extends to pelvic wall and/or involves lower third of vagina, and/or causes hydronephrosis or nonfunctioning kidney. (from AJCC 7th Ed.)
Cervical cancer involves lower third of vagina, without extension to pelvic wall. (from AJCC 7th Ed.)
Cervical cancer extends to pelvic wall and/or causes hydronephrosis or nonfunctioning kidney. (from AJCC 7th Ed.)
Cervical cancer invades mucosa of bladder or rectum, and/or extends beyond true pelvis (bullous edema is not sufficient to classify a tumor as T4). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Cervical cancer in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Cervical cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Cervical cancer with regional lymph node metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Cervical cancer in which there is no evidence of distant metastasis. (from AJCC 7th Ed.)
Cervical cancer with distant metastasis (including peritoneal spread, involvement of supraclavicular, mediastinal, or paraaortic lymph nodes, lung, liver, or bone). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Cervical cancer with a finding of carcinoma in situ (preinvasive carcinoma). Note: FIGO no longer includes Stage 0 (Tis) (from AJCC 7th Ed.)
Invasive cervical cancer diagnosed only by microscopy. Stromal invasion with a maximum depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less. Vascular space involvement, venous or lymphatic, does not affect classification. (from AJCC 7th Ed.)
Invasive cervical cancer with measured stromal invasion 3.0 mm or less in depth and 7.0 mm or less in horizontal spread. (from AJCC 7th Ed.)
Invasive cervical cancer with measured stromal invasion more than 3.0 mm and not more than 5.0 mm with a horizontal spread 7.0 mm or less. (from AJCC 7th Ed.)
Cervical cancer with microscopic lesion greater than T1a/IA2. (from AJCC 7th Ed.)
Stage II includes: IIA (T1, N1, M0) and IIB (T2, N1, M0) or (T3, N0, M0). T1: Tumor is 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, and without bronchoscopic evidence of invasion more proximal than the lobar bronchus. T2: Tumor has any of the following features of size or extent: more than 3 cm in greatest dimension; involves the main bronchus, 2 cm or more distal to the carina; invades the visceral pleura; associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung. T3: Tumor (of any size) directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium; or tumor in the main bronchus less than 2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung. N0: No regional lymph node metastasis. N1: Metastasis to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and intrapulmonary nodes including involvement by direct extension of the primary tumor. M0: No distant metastasis. (AJCC 6th ed.)
A pathologic finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for cervical cancer. (from AJCC 7th Ed.)
A finding about one or more characteristics of uterine corpus cancer, following the rules of the TNM AJCC v7 classification system. The TNM findings for uterine corpus carcinomas and sarcomas are not the same. (from AJCC 7th Ed.)
A finding about one or more characteristics of uterine corpus carcinoma, following the rules of the TNM AJCC v7 classification system. Carcinosarcomas should be staged as carcinoma. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of uterine corpus carcinoma, following the rules of the TNM AJCC v7 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of uterine corpus carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
Uterine corpus carcinoma in which primary tumor cannot be assessed. (from AJCC 7th Ed.)
Uterine corpus carcinoma in which there is no evidence of a primary tumor. (from AJCC 7th Ed.)
Uterine corpus carcinoma with a finding of carcinoma in situ (preinvasive carcinoma). FIGO no longer includes Stage 0 (Tis). (from AJCC 7th Ed.)
Uterine corpus carcinoma with tumor confined to uterine corpus. (from AJCC 7th Ed.)
Uterine corpus carcinoma with tumor limited to endometrium or invading less than one-half of the myometrium. (from AJCC 7th Ed.)
Uterine corpus carcinoma with tumor invading one-half or more of the myometrium. (from AJCC 7th Ed.)
Uterine corpus carcinoma that invades stromal connective tissue of the cervix but does not extend beyond uterus. Endocervical glandular involvement only should be considered as Stage I and not as Stage II. (from AJCC 7th Ed.)
Uterine corpus carcinoma that involves serosa and/or adnexa, vagina, or parametrial tissue. (from AJCC 7th Ed.)
Uterine corpus carcinoma that involves serosa and/or adnexa (direct extension or metastasis). (from AJCC 7th Ed.)
Uterine corpus carcinoma that involves vagina or parametrial tissue. (from AJCC 7th Ed.)
Uterine corpus carcinoma that invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of uterine corpus carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes. TNM pathologic regional lymph nodes findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
Uterine corpus carcinoma in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Uterine corpus carcinoma with no evidence of regional lymph node metastasis. (from AJCC 7th Ed.)
Uterine corpus carcinoma with regional lymph node metastasis to pelvic lymph nodes. (from AJCC 7th Ed.)
Uterine corpus carcinoma with regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of uterine corpus carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for uterine corpus carcinoma. (from AJCC 7th Ed.)
Uterine corpus carcinoma with distant metastasis (includes metastasis to inguinal lymph nodes intraperitoneal disease, or lung, liver, or bone. It excludes metastasis to para-aortic lymph nodes, vagina, pelvic serosa, or adnexa). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of uterine corpus carcinoma, following the rules of the TNM AJCC v7 classification system. TNM clinical findings are based on information obtained prior to the first definitive treatment through physical examination, diagnostic imaging, biopsy and laboratory testing.
A clinical finding about one or more characteristics of uterine corpus carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. (from AJCC 7th Ed.)
Uterine corpus carcinoma with no distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of uterine corpus sarcoma, following the rules of the TNM AJCC v7 classification system. It applies to leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma. (from AJCC 7th Ed.)
A finding about one or more characteristics of leiomyosarcoma and endometrial stromal sarcoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of leiomyosarcoma and endometrial stromal sarcoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of leiomyosarcoma and endometrial stromal sarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Tumor limited to the uterus. (from AJCC 7th Ed.)
Tumor 5 cm or less in greatest dimension. (from AJCC 7th Ed.)
Tumor more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
Tumor extends beyond the uterus, within the pelvis. (from AJCC 7th Ed.)
Stage IV includes: (T4, Any N, M0); (Any T, N3, M0); (Any T, Any N, M1). T4: Tumor invades other adjacent structures. N3: Metastasis in deep inguinal or pelvic lymph node(s) unilateral or bilateral. M1: Distant metastasis. (AJCC 6th ed.) - 2003
Tumor involves adnexa. (from AJCC 7th Ed.)
Tumor involves other pelvic tissues. (from AJCC 7th Ed.)
Tumor infiltrates abdominal tissues. (from AJCC 7th Ed.)
Tumor infiltrates abdominal tissues, one site. (from AJCC 7th Ed.)
Tumor infiltrates abdominal tissues, more than one site. (from AJCC 7th Ed.)
Tumor invades bladder or rectum. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of leiomyosarcoma and endometrial stromal sarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the regional lymph nodes.
Regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
No regional lymph node metastasis. (from AJCC 7th Ed.)
Regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of leiomyosarcoma and endometrial stromal sarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0. (from AJCC 7th Ed.)
Distant metastasis (excluding adnexa, pelvic and abdominal tissues). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of leiomyosarcoma and endometrial stromal sarcoma, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of leiomyosarcoma and endometrial stromal sarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. (from AJCC 7th Ed.)
No distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of adenosarcoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of adenosarcoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of adenosarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Tumor limited to endometrium/endocervix. (from AJCC 7th Ed.)
Tumor invades to less than half of the myometrium. (from AJCC 7th Ed.)
Tumor invades more than half of the myometrium. (from AJCC 7th Ed.)
Tumor involves abdominal tissues. (from AJCC 7th Ed.)
Tumor involves abdominal tissues, one site. (from AJCC 7th Ed.)
Tumor invades abdominal tissues, more than one site. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of adenosarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the regional lymph nodes.
A pathologic finding about one or more characteristics of adenosarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of adenosarcoma, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of adenosarcoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. (from AJCC 7th Ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. FIGO no longer includes Stage 0 (Tis). (AJCC 7th ed.)
Stage I includes: I (T1, N0, M0); IA: (T1a, N0, M0); IB (T1b, N0, M0). T1: Tumor confined to corpus uteri. T1a: Tumor limited to the endometrium or invades less than one-half of the myometrium. T1b: Tumor invades one-half or more of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus. Endocervical glandular involvement only should be considered as Stage I and not as Stage II. N0: No regional lymph node metastasis. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage III includes: III (T3, N0, M0); IIIA (T3a, N0, M0); IIIB (T3b, N0, M0); IIIC (T1-T3, N1/N2, M0); IIIC1 (T1-T3, N1, M0); IIIC2 (T1-T3, N2, M0). T3: Tumor involves serosa and/or adnexa, vagina, or parametrial tissue. T3a: Tumor involves serosa and/or adnexa (direct extension or metastasis). T3b: Tumor involves vagina (direct extension or metastasis) or parametrial tissue. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis to pelvic lymph nodes. N2: Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IV includes: IVA: (T4, Any N, M0); IVB: (Any T, Any N, M1). T4: Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4). M0: No distant metastasis. M1: Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, or lung, liver, or bone. It excludes metastasis to para-aortic lymph nodes, vagina, pelvic serosa, or adnexa). This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
A finding about one or more characteristics of ovarian cancer or primary peritoneal carcinoma, following the rules of the TNM AJCC v7 classification system. Ovarian cancer and primary peritoneal carcinoma are surgically/pathologically staged malignancies. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ovarian cancer or primary peritoneal carcinoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of ovarian cancer or primary peritoneal carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Ovarian cancer or primary peritoneal carcinoma in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma with no evidence of primary tumor. (from AJCC 7th Ed.)
Ovarian cancer limited to ovaries (one or both). (from AJCC 7th Ed.)
Ovarian cancer limited to one ovary; capsule intact, no tumor on ovarian surface. No malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
Ovarian cancer limited to both ovaries; capsule intact, no tumor on ovarian surface. No malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma limited to one or both ovaries with any of the following: capsule ruptured, tumor on ovarian surface, malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma involving one or both ovaries with pelvic extension. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma with extension and/or implants on uterus and/or tube(s). No malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma with extension to and/or implants on other pelvic tissues. No malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma with pelvic extension and/or implants (T2a or T2b) with malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma involving one or both ovaries with microscopically confirmed peritoneal metastasis outside the pelvis. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma with microscopic peritoneal metastasis beyond pelvis (no macroscopic tumor). (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma with macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma with peritoneal metastasis beyond pelvis more than 2 cm in greatest dimension and/or regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ovarian cancer or primary peritoneal carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Ovarian cancer or primary peritoneal carcinoma in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma without regional lymph node metastasis. (from AJCC 7th Ed.)
Ovarian cancer or primary peritoneal carcinoma with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ovarian cancer or primary peritoneal carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for ovarian cancer or primary peritoneal carcinoma.
Ovarian cancer or primary peritoneal carcinoma with distant metastasis (excludes peritoneal metastasis). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of ovarian cancer or primary peritoneal carcinoma, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of ovarian cancer or primary peritoneal carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Ovarian cancer or primary peritoneal carcinoma without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of fallopian tube cancer, following the rules of the TNM AJCC v7 classification system. Histologic confirmation of primary disease with complete evaluation of the abdomen and pelvis is required. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of fallopian tube cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of fallopian tube cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Fallopian tube cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Fallopian tube cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Fallopian tube cancer with a finding of carcinoma in situ (limited to tubal mucosa). (from AJCC 7th Ed.)
Fallopian tube cancer limited to fallopian tube(s). (from AJCC 7th Ed.)
Fallopian tube cancer with tumor limited to one tube, without penetrating the serosal surface; no ascites. (from AJCC 7th Ed.)
Fallopian tube cancer with tumor limited to both tubes, without penetrating the serosal surface; no ascites. (from AJCC 7th Ed.)
Fallopian tube cancer with tumor limited to one or both tubes with extension onto or through the tubal serosa, or with malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
Fallopian tube cancer with tumor involving one or both fallopian tubes with pelvic extension. (from AJCC 7th Ed.)
Fallopian tube cancer with extension and/or metastasis to the uterus and/or ovaries. (from AJCC 7th Ed.)
Fallopian tube cancer with extension to other pelvic structures. (from AJCC 7th Ed.)
Fallopian tube cancer with pelvic extension and malignant cells in ascites or peritoneal washings. (from AJCC 7th Ed.)
Fallopian tube cancer with tumor involving one or both fallopian tubes, with peritoneal implants outside the pelvis. (from AJCC 7th Ed.)
Fallopian tube cancer with microscopic peritoneal metastasis outside the pelvis. (from AJCC 7th Ed.)
Fallopian tube cancer with macroscopic peritoneal metastasis outside the pelvis 2 cm or less in greatest dimension. (from AJCC 7th Ed.)
Fallopian tube cancer with peritoneal metastasis outside the pelvis and more than 2 cm in diameter. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of fallopian tube cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Fallopian tube cancer in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Fallopian tube cancer without regional lymph node metastasis. (from AJCC 7th Ed.)
Fallopian tube cancer with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of fallopian tube cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for fallopian tube cancer.
Fallopian tube cancer with distant metastasis (excluding metastasis within the peritoneal cavity). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of fallopian tube cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of fallopian tube cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Fallopian tube cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of gestational trophoblastic tumor, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of gestational trophoblastic tumor, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of gestational trophoblastic tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Gestational trophoblastic tumor in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Gestational trophoblastic tumor with no evidence of primary tumor. (from AJCC 7th Ed.)
Gestational trophoblastic tumor confined to uterus. (from AJCC 7th Ed.)
Gestational trophoblastic tumor extending to other genital structures (ovary, tube, vagina, broad ligaments) by metastasis or direct extension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gestational trophoblastic tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for gestational trophoblastic tumor.
Gestational trophoblastic tumor with distant metastasis. (from AJCC 7th Ed.)
Gestational trophoblastic tumor with lung metastasis. (from AJCC 7th Ed.)
Gestational trophoblastic tumor with all other distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of gestational trophoblastic tumor, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of gestational trophoblastic tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Gestational trophoblastic tumor without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of digestive system cancer, following the rules of the TNM AJCC v7 classification system.
A somatic mutation of the GNAQ gene which encodes guanine nucleotide-binding protein G(q) subunit alpha.
A somatic mutation of the GNA11 gene which encodes guanine nucleotide-binding protein subunit alpha-11.
A finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v7 classification system. Tumor location is simplified, and esophagogastric junction and proximal 5 cm of stomach are included in this classification. Nonmucosal cancers are not included. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v7 classification system. The pathologic classification uses evidence acquired before treatment, supplemented or modified by additional evidence acquired during and from surgery, particularly from pathologic evaluation of the surgical specimen. Pathologic reclassification during and following surgery that has been preceded by chemotherapy and/or radiotherapy is designated by the prefix yp. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Esophagus and esophagogastric junction cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with no evidence of a primary tumor. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with a finding of high-grade dysplasia. High-grade dysplasia includes all noninvasive neoplastic epithelia that was formerly called carcinoma in situ, a diagnosis that is no longer used for columnar mucosae anywhere in the gastrointestinal tract. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading lamina propria, muscularis mucosae, or submucosa. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading lamina propria or muscularis mucosae. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading submucosa. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading muscularis propria. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading adventitia. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading adjacent structures. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with resectable tumor invading pleura, pericardium, or diaphragm. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Esophagus and esophagogastric junction cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with no metastasis to regional lymph nodes. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with metastasis in 1-2 regional lymph nodes. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with metastasis in 3-6 regional lymph nodes. (from AJCC 7th Ed.)
Esophagus and esophagogastric junction cancer with metastasis in seven or more lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for esophagus and esophagogastric junction cancer.
Esophagus and esophagogastric junction cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v7 classification system. Clinical classification is based on evidence before primary treatment. It involves esophagoscopy with biopsy, endoscopic esophageal ultrasound (EUS), EUS-directed fine-needle aspiration (EUS-FNA), fused computed tomography (CT), PET/CT for assessment of T, N, M, and G classifications, and histopathologic type. Clinical reclassification during or following chemotherapy and/or radiotherapy is designated by the prefix yc. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Esophagus and esophagogastric junction cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Any type of genetic recombination involving rearrangement of segments of DNA within a single chromosome, such that a segment of the chromosome is reversed from the original orientation. Chromosomal inversion often occurs as the result of non-homologous end-joining of broken DNA strands, and is involved in maintaining cell viability at the expense of long term genomic stability. This process may be involved in infertility.
Any DNA sequence alteration process occurring in a tumor suppressor gene, resulting in loss of function of the gene product, and predisposing the cell to neoplastic transformation. Tumor suppressor genes are ordinarily involved in repressing cell cycle or promoting apoptosis. Inactivation of such genes permits growth inappropriately, and is an important step in the process of cellular transformation.
A carcinoma that originates from the colonic wall and has spread to the lungs.
A finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v7 classification system. Tumors arising at the esophagogastric junction, or arising in the stomach in a distance equal or less than 5 cm from the esophagogastric junction and crossing the esophagogastric junction are staged using the TNM system for esophageal adenocarcinoma. Lymphomas, sarcomas, and carcinoid tumors (low-grade neuroendocrine tumors) are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging depends on data acquired clinically, together with findings on subsequent surgical exploration and examination of the pathologic specimen if resection is accomplished. Pathologic assessment of the regional lymph nodes entails their removal and histologic examination to evaluate the total number, as well as the number that contain metastatic tumor. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Gastric cancer invading lamina propria, muscularis mucosae, or submucosa. (from AJCC 7th Ed.)
Gastric cancer with tumor invading lamina propria or muscularis mucosae. (from AJCC 7th Ed.)
Gastric cancer invading the submucosa. (from AJCC 7th Ed.)
Gastric cancer with tumor invading the muscularis propria. A tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum, without perforation of the visceral peritoneum covering these structures. In this case, the tumor is classified T3. If there is perforation of the visceral peritoneum covering the gastric ligaments or the omentum, the tumor should be classified T4. (from AJCC 7th Ed.)
Gastric cancer with tumor penetrating subserosal connective tissue without invasion of visceral peritoneum or adjacent structures. The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. Intramural extension to the duodenum or esophagus is classified by the depth of the greatest invasion in any of these sites, including the stomach. (from AJCC 7th Ed.)
Gastric cancer with tumor invading serosa (visceral peritoneum) or adjacent structures. The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. Intramural extension to the duodenum or esophagus is classified by the depth of the greatest invasion in any of these sites, including the stomach. (from AJCC 7th Ed.)
Gastric cancer with tumor invading serosa (visceral peritoneum). (from AJCC 7th Ed.)
Gastric cancer with tumor invading adjacent structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Gastric cancer without regional lymph node metastasis. Note: A designation of pN0 should be used if all examined lymph nodes are negative, regardless of the total number removed and examined. (from AJCC 7th Ed.)
Gastric cancer with metastasis in 1-2 regional lymph nodes. (from AJCC 7th Ed.)
Gastric cancer with metastasis in 3-6 regional lymph nodes. (from AJCC 7th Ed.)
Gastric cancer with metastasis in seven or more regional lymph nodes. (from AJCC 7th Ed.)
Gastric cancer with metastasis in 7-15 regional lymph nodes. (from AJCC 7th Ed.)
Gastric cancer with metastasis in sixteen or more regional lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for gastric cancer. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v7 classification system. The clinical staging is based on evidence of extent of disease acquired before definitive treatment is instituted. It includes physical examination, radiologic imaging, endoscopy, biopsy, and laboratory findings. All cancers should be confirmed histologically. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Gastric cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Gastric cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v7 classification system. Lymphomas, carcinoid tumors, and visceral sarcomas are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v7 classification system. The primary tumor is staged according to its depth of penetration and the involvement of adjacent structures or distant sites. Lateral spread within the duodenum, jejunum, or ileum is not considered in this classification. Only the depth of tumor penetration into the bowel wall and spread to other structures defines the pT stage. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Small intestine cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Small intestine cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Small intestine cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Small intestine cancer with tumor invading lamina propria or submucosa. (from AJCC 7th Ed.)
Small intestine cancer with tumor invading lamina propria. (from AJCC 7th Ed.)
Small intestine cancer with tumor invading the submucosa. Note: The nonperitonealized perimuscular tissue is, for jejunum and ileum, part of the mesentery and, for duodenum in areas where serosa is lacking, part of the interface with the pancreas. (from AJCC 7th Ed.)
Small intestine cancer with tumor invading muscularis propria. (from AJCC 7th Ed.)
Small intestine cancer with tumor invading through the muscularis propria into the subserosa or into the nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less. Note: The nonperitonealized perimuscular tissue is, for jejunum and ileum, part of the mesentery and, for duodenum in areas where serosa is lacking, part of the interface with the pancreas. (from AJCC 7th Ed.)
Small intestine cancer with tumor perforating the visceral peritoneum or directly invading other organs or structures (including other loops of small intestine, mesentery, or retroperitoneum more than 2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Small intestine cancer in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Small intestine cancer without regional lymph node metastasis. (from AJCC 7th Ed.)
Small intestine cancer with metastasis in 1-3 regional lymph nodes. (from AJCC 7th Ed.)
Small intestine cancer with metastasis in four or more regional lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for small intestine cancer. (from AJCC 7th Ed.)
Small intestine cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v7 classification system. Imaging studies such as CT and MRI play a major role in clinical staging. Metastatic disease is assessed by routine chest films and chest CT. Intraoperative assessment plays a role in clinical evaluation, especially when tumor cannot be resected. Metastatic involvement of the liver may be evaluated by intraoperative ultrasonography. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Small intestine cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of appendiceal cancer, following the rules of the TNM AJCC v7 classification system. Carcinomas and carcinoid tumors of the appendix are included, but are separately categorized. (from AJCC 7th Ed.)
A finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v7 classification system. Appendiceal carcinomas are usually staged after surgical exploration of the abdomen and pathologic examination of the resected specimen. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Appendiceal carcinoma in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Appendiceal carcinoma with no evidence of primary tumor. (from AJCC 7th Ed.)
Appendiceal carcinoma with a finding of carcinoma in situ: intraepithelial or invasion of the lamina propria. Tis includes cancer cells confined within the glandular basement membrane (intraepithelial) or lamina propria (intramucosal) with no extension through muscularis mucosae into submucosa. (from AJCC 7th Ed.)
Appendiceal carcinoma with tumor invading submucosa. (from AJCC 7th Ed.)
Appendiceal carcinoma with tumor invading muscularis propria. (from AJCC 7th Ed.)
Appendiceal carcinoma with tumor invading through muscularis propria into subserosa or into mesoappendix. (from AJCC 7th Ed.)
Appendiceal carcinoma with tumor penetrating visceral peritoneum including mucinous peritoneal tumor within the right lower quadrant and/or directly invading other organs or structures. Direct invasion in T4 includes invasion of other segments of the colorectum by way of the serosa, e.g., invasion of ileum. Tumor that is adherent to other organs or structures grossly is classified cT4b. However, if no tumor is present in the adhesion microscopically, the classification should be pT1-3 depending on the anatomical depth of wall invasion. (from AJCC 7th Ed.)
Appendiceal carcinoma with tumor penetrating visceral peritoneum including mucinous peritoneal tumor within the right lower quadrant. (from AJCC 7th Ed.)
Appendiceal carcinoma with tumor directly invading other organs or structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Appendiceal carcinoma in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Appendiceal carcinoma without regional lymph node metastasis. (from AJCC 7th Ed.)
Appendiceal carcinoma with metastasis in 1-3 regional lymph nodes. (from AJCC 7th Ed.)
Appendiceal carcinoma with metastasis in four or more regional lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for appendiceal carcinoma. (from AJCC 7th Ed.)
Appendiceal carcinoma with distant metastasis. (from AJCC 7th Ed.)
Appendiceal carcinoma with intraperitoneal metastasis beyond the right lower quadrant, including pseudomyxoma peritonei. (from AJCC 7th Ed.)
Appendiceal carcinoma with nonperitoneal metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v7 classification system. Clinical assessment is based on medical history, physical examination, and imaging. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Appendiceal carcinoma without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of appendiceal carcinoid, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of appendiceal carcinoid, following the rules of the TNM AJCC v7 classification system. Appendiceal carcinoids are usually staged after laparoscopic or open surgical exploration of the abdomen (often for appendicitis) and pathologic examination of the resected specimen. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoid, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Appendiceal carcinoid in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Appendiceal carcinoid with no evidence of primary tumor. (from AJCC 7th Ed.)
Appendiceal carcinoid with tumor 2 cm or less in greatest dimension. (from AJCC 7th Ed.)
Appendiceal carcinoid with tumor 1 cm or less in greatest dimension. (from AJCC 7th Ed.)
Appendiceal carcinoid with tumor more than 1 cm but not more than 2 cm in greatest dimension. (from AJCC 7th Ed.)
Appendiceal carcinoid with tumor more than 2 cm but not more than 4 cm or with extension to the cecum. (from AJCC 7th Ed.)
Appendiceal carcinoid with tumor more than 4 cm or with extension to the ileum. (from AJCC 7th Ed.)
Appendiceal carcinoid with tumor directly invading other adjacent organs or structures, e.g., abdominal wall and skeletal muscle. Penetration of the mesoappendix does not seem to be as important a prognostic factor as the size of the primary tumor and is not separately categorized. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoid, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Appendiceal carcinoid in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Appendiceal carcinoid without regional lymph node metastasis. (from AJCC 7th Ed.)
Appendiceal carcinoid with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoid, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for appendiceal carcinoid. (from AJCC 7th Ed.)
Appendiceal carcinoid with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of appendiceal carcinoid, following the rules of the TNM AJCC v7 classification system. Clinical assessment is based on medical history, physical examination, and imaging. Determination of elevated urinary 5-HIAA may indicate liver metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of appendiceal carcinoid, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Appendiceal carcinoid without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v7 classification system. Sarcomas, lymphomas, and carcinoid tumors of the large intestine are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v7 classification system. Most cancers of the colon and many cancers of the rectum are pathologically staged after surgical exploration of the abdomen, cancer-directed surgical resection, and pathologic examination of the resected specimen. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Colorectal cancer with a finding of carcinoma in situ: intraepithelial or invasion of lamina propria. Note: Tis includes cancer cells confined within the glandular basement membrane (intraepithelial) or mucosal lamina propria (intramucosal) with no extension through the muscularis mucosae into the submucosa. (from AJCC 7th Ed.)
Colorectal cancer with invasion through the muscularis propria into pericolorectal tissues. (from AJCC 7th Ed.)
Colorectal cancer with penetration to the surface of the visceral peritoneum. (from AJCC 7th Ed.)
Colorectal cancer with direct invasion or adherence to other organs or structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Colorectal cancer with metastasis in 1-3 regional lymph nodes. (from AJCC 7th Ed.)
Colorectal cancer with metastasis in one regional lymph node. (from AJCC 7th Ed.)
Colorectal cancer with metastasis in 2-3 regional lymph nodes. (from AJCC 7th Ed.)
Colorectal cancer with tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional lymph node metastasis. (from AJCC 7th Ed.)
Colorectal cancer with metastasis in four or more regional lymph nodes. (from AJCC 7th Ed.)
Colorectal cancer with metastasis in 4-6 regional lymph nodes. (from AJCC 7th Ed.)
Colorectal cancer with metastasis in seven or more regional lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for colorectal cancer. (from AJCC 7th Ed.)
Colorectal cancer with metastasis confined to one organ or site (e.g., liver, lung, ovary, nonregional node). (from AJCC 7th Ed.)
Colorectal cancer with metastases in more than one organ/site or the peritoneum. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v7 classification system. Clinical assessment is based on medical history, physical examination, sigmoidoscopy, and colonoscopy with biopsy. Examinations designed to demonstrate the presence of extrarectal or extracolonic metastasis may include chest radiographic films, computed tomography (CT; abdomen, pelvis, chest), magnetic resonance imaging (MRI), and positron emission tomography (PET) or fused PET/CT scans. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Colorectal cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Colorectal cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v7 classification system. This classification applies to carcinomas arising in the anal canal only; melanomas, carcinoid tumors, sarcomas, and perianal tumors are not included. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for anal cancer. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v7 classification system. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Anal cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Anal cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Gastrointestinal stromal tumor in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Gastrointestinal stromal tumor with no evidence of a primary tumor. (from AJCC 7th Ed.)
Gastrointestinal stromal tumor with tumor size 2 cm or less in greatest dimension. (from AJCC 7th Ed.)
Gastrointestinal stromal tumor with tumor size more than 2 cm, but not more than 5 cm, in greatest dimension. (from AJCC 7th Ed.)
Gastrointestinal stromal tumor with tumor size more than 5 cm, but not more than 10 cm, in greatest dimension. (from AJCC 7th Ed.)
Gastrointestinal stromal tumor with tumor size more than 10 cm in greatest dimension. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Gastrointestinal stromal tumor in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Gastrointestinal stromal tumor with no evidence of metastasis to regional lymph nodes. (from AJCC 7th Ed.)
Gastrointestinal stromal tumor with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for gastrointestinal stromal tumor. (from AJCC 7th Ed.)
Gastrointestinal stromal tumor with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Gastrointestinal stromal tumor without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of gastrointestinal neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system. This classification applies to gastric, small bowel, colonic, rectal, and ampulla of Vater carcinoid tumors; carcinoid tumors of the appendix and neuroendocrine tumors of the pancreas are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastrointestinal neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system. The pathologic staging is based on endoscopic biopsy specimens, percutaneous biopsies, fine-needle aspirates, surgical exploration, and on examination of surgically resected primary tumor, lymph nodes, and distant metastases. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastric neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Gastric neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor with no evidence of a primary tumor. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor with a finding of carcinoma in situ/dysplasia (tumor size less than 0.5 mm), confined to mucosa. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor invading lamina propria or submucosa and is 1 cm or less in size. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor invading muscularis propria or is more than 1 cm in size. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor penetrating subserosa. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor invading visceral peritoneum (serosa) or other organs or adjacent structures. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastric neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Gastric neuroendocrine tumor in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor with no regional lymph node metastasis. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gastric neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for gastric neuroendocrine tumor. (from AJCC 7th Ed.)
Gastric neuroendocrine tumor with distant metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of duodenum/ampulla/jejunum/ileum neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor with no evidence of a primary tumor. (from AJCC 7th Ed.)
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor invading lamina propria or submucosa and is 1 cm or less in size (small intestinal tumors); for ampullary tumors: tumor 1 cm or less. (from AJCC 7th Ed.)
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor invading muscularis propria or is more than 1 cm in size (small intestinal tumors); for ampullary tumors: tumor more than 1 cm. (from AJCC 7th Ed.)
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa (jejunal or ileal tumors) or invading pancreas or retroperitoneum (ampullary or duodenal tumors) or into non-peritonealized tissues. (from AJCC 7th Ed.)
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor invading visceral peritoneum (serosa) or invading other organs. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of duodenum/ampulla/jejunum/ileum neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor with no regional lymph node metastasis. (from AJCC 7th Ed.)
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of duodenum/ampulla/jejunum/ileum neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for duodenum/ampulla/jejunum/ileum neuroendocrine tumor. (from AJCC 7th Ed.)
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor with distant metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of colon or rectum neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Colon or rectum neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor with no evidence of a primary tumor. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor invading lamina propria or submucosa and is 2 cm or less in size. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor invading lamina propria or submucosa and is less than 1 cm in greatest dimension. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor invading lamina propria or submucosa and is 1-2 cm in greatest dimension. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor invading muscularis propria or is more than 2 cm in size with invasion of lamina propria or submucosa. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor invading through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor invading peritoneum or other organs. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of colon or rectum neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Colon or rectum neuroendocrine tumor in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor with no regional lymph node metastasis. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of colon or rectum neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for colon or rectum neuroendocrine tumor. (from AJCC 7th Ed.)
Colon or rectum neuroendocrine tumor with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of gastrointestinal neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system. The clinical staging depends upon the anatomic extent and hormonal activity of the primary tumor, which can be ascertained by examination before treatment. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of gastric neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Gastric neuroendocrine tumor without evidence of distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of duodenum/ampulla/jejunum/ileum neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Duodenum/ampulla/jejunum/ileum neuroendocrine tumor without evidence of distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of colon or rectum neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Colon or rectum neuroendocrine tumor without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v7 classification system. Intrahepatic bile duct cancers are no longer included in this classification. The staging of liver cancer now includes only hepatocellular carcinoma. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v7 classification system. Complete pathologic staging consists of evaluation of the primary tumor, including histologic grade, regional lymph node status, and underlying liver disease. Regional lymph node involvement is rare (5%) except in the fibrolamellar variant of hepatocellular carcinoma. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Liver cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Liver cancer with no evidence of a primary tumor. (from AJCC 7th Ed.)
Liver cancer with solitary tumor without vascular invasion. (from AJCC 7th Ed.)
Liver cancer with solitary tumor with vascular invasion or multiple tumors none more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
Liver cancer with multiple tumors more than 5 cm in greatest dimension. (from AJCC 7th Ed.)
Liver cancer with single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein. (from AJCC 7th Ed.)
Liver cancer with tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Liver cancer in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Liver cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Liver cancer with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for liver cancer. (from AJCC 7th Ed.)
A disease that does not go to remission despite treatment.
Liver cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v7 classification system.
A clinical finding about one or more characteristics of liver cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Liver cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v7 classification system. This is a novel staging system and applies only to intrahepatic cholangiocarcinomas and the rare combined hepatocellular and cholangiocarcinomas. Pure hepatocellular carcinomas are not included in this classification. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v7 classification system. Complete pathologic staging consists of evaluation of the primary tumor, including tumor number, involvement of local regional lymph nodes, and the presence or absence of vascular invasion. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Intrahepatic bile duct cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Intrahepatic bile duct cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Intrahepatic bile duct cancer with a finding of carcinoma in situ (intraductal tumor). (from AJCC 7th Ed.)
Intrahepatic bile duct cancer with solitary tumor without vascular invasion. (from AJCC 7th Ed.)
Intrahepatic bile duct cancer with solitary tumor with vascular invasion or multiple tumors, with or without vascular invasion.
Intrahepatic bile duct cancer with solitary tumor with vascular invasion. (from AJCC 7th Ed.)
Intrahepatic bile duct cancer with multiple tumors, with or without vascular invasion. (from AJCC 7th Ed.)
Intrahepatic bile duct cancer with tumor perforating the visceral peritoneum or involving the local extra hepatic structures by direct invasion. (from AJCC 7th Ed.)
Intrahepatic bile duct cancer with periductal invasion. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Intrahepatic bile duct cancer in which regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Intrahepatic bile duct cancer without regional lymph node metastasis. (from AJCC 7th Ed.)
Intrahepatic bile duct cancer with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for intrahepatic bile duct cancer.
Intrahepatic bile duct cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v7 classification system. The clinical staging depends on imaging procedures. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Intrahepatic bile duct cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v7 classification system. Carcinoid tumors and sarcomas are not included. The cystic duct is now included in this classification scheme. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging is based on examination of the surgical resection specimen. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Gallbladder cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Gallbladder cancer with metastases to nodes along the cystic duct, common bile duct, hepatic artery, and/or portal vein. (from AJCC 7th Ed.)
Gallbladder cancer with metastases to periaortic, pericaval, superior mesenteric artery, and/or celiac artery lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for gallbladder cancer.
A clinical finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v7 classification system. The clinical evaluation usually depends on the results of ultrasonography, computed tomography, and magnetic resonance cholangiopancreatography. Clinical staging may also be based on findings from surgical exploration (laparoscopic or open) when the main tumor mass is not resected. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Gallbladder cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
Gallbladder cancer with distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v7 classification system. Sarcomas and carcinoid tumors are not included. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging is based on examination of the resected specimen and/or biopsies sufficient to document the greatest extent of the disease. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Perihilar bile duct cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Perihilar bile duct cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Perihilar bile duct cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Perihilar bile duct cancer with tumor confined to the bile duct, with extension up to the muscle layer or fibrous tissue. (from AJCC 7th Ed.)
Perihilar bile duct cancer with tumor invading beyond the wall of the bile duct to surrounding adipose tissue or tumor invading adjacent hepatic parenchyma. (from AJCC 7th Ed.)
Perihilar bile duct cancer with tumor invading beyond the wall of the bile duct to surrounding adipose tissue. (from AJCC 7th Ed.)
Perihilar bile duct cancer with tumor invading adjacent hepatic parenchyma. (from AJCC 7th Ed.)
Perihilar bile duct cancer with tumor invading unilateral branches of the portal vein or hepatic artery. (from AJCC 7th Ed.)
Perihilar bile duct cancer with tumor invading the main portal vein or its branches bilaterally; or the common hepatic artery; or the second-order biliary radicals bilaterally; or unilateral second-order biliary radicals with contralateral portal vein or hepatic artery involvement. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Perihilar bile duct cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Perihilar bile duct cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Perihilar bile duct cancer with regional lymph node metastasis (including nodes along the cystic duct, common bile duct, hepatic artery, and portal vein). (from AJCC 7th Ed.)
Perihilar bile duct cancer with metastasis to periaortic, pericaval, superior mesenteric artery, and/or celiac artery lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for perihilar bile duct cancer.
Perihilar bile duct cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v7 classification system. The clinical evaluation usually depends on the results of duplex ultrasound, computed tomography, and magnetic resonance cholangiopancreatography (MRCP). The biliary extent of disease is assessed with percutaneous transhepatic cholangiography or MRCP. Clinical staging also may be based on findings from surgical exploration when the main tumor mass is not resected. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Perihilar bile duct cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v7 classification system. This TNM classification applies only to cancers arising in the extrahepatic bile ducts above the ampulla of Vater. Sarcomas and carcinoid tumors are not included. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging is based on surgical resection and pathologic examination of the specimen and associated lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Distal bile duct cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Distal bile duct cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Distal bile duct cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Distal bile duct cancer with tumor confined to the bile duct histologically. (from AJCC 7th Ed.)
Distal bile duct cancer with tumor invading beyond the wall of the bile duct. (from AJCC 7th Ed.)
Distal bile duct cancer with tumor invading the gallbladder, pancreas, duodenum, or other adjacent organs without involvement of the celiac axis or the superior mesenteric artery. (from AJCC 7th Ed.)
Distal bile duct cancer with tumor involving the celiac axis or the superior mesenteric artery. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Distal bile duct cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Distal bile duct cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Distal bile duct cancer with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for distal bile duct cancer. (from AJCC 7th Ed.)
Distal bile duct cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v7 classification system. The clinical evaluation usually depends on the results of ultrasonography, contrast-enhanced multidetector computerized tomography (CT), or magnetic resonance cholangiopancreatography (MRCP), including arterial and portal venous phases, with thin sections whenever possible. Clinical staging may also be based on findings from surgical exploration when the main tumor mass is not resected. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Distal bile duct cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v7 classification system. The pathologic staging depends on surgical resection and pathologic examination of the specimen and associated lymph nodes. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Ampulla of Vater cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Ampulla of Vater cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Ampulla of Vater cancer with a finding of carcinoma in situ. (from AJCC 7th Ed.)
Ampulla of Vater cancer with tumor limited to ampulla of Vater or sphincter of Oddi. (from AJCC 7th Ed.)
Ampulla of Vater cancer with tumor invading the duodenal wall. (from AJCC 7th Ed.)
Ampulla of Vater cancer with tumor invading the pancreas. (from AJCC 7th Ed.)
Ampulla of Vater cancer with tumor invading peripancreatic soft tissues or other adjacent organs or structures other than pancreas. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Ampulla of Vater cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Ampulla of Vater cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Ampulla of Vater cancer with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for ampulla of Vater cancer. (from AJCC 7th Ed.)
Ampulla of Vater cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v7 classification system. Endoscopic ultrasonography and computed tomography are effective in preoperative staging and in evaluating resectability of ampullary carcinomas. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Ampulla of Vater cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding about one or more characteristics of exocrine or endocrine pancreatic cancer, following the rules of the TNM AJCC v7 classification system. Pancreatic neuroendocrine tumors (including carcinoid tumors) are now staged by a single pancreatic staging system. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of exocrine or endocrine pancreatic cancer, following the rules of the TNM AJCC v7 classification system.
A pathologic finding about one or more characteristics of exocrine or endocrine pancreatic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of the primary tumor.
Exocrine or endocrine pancreatic cancer in which the primary tumor cannot be assessed. (from AJCC 7th Ed.)
Exocrine or endocrine pancreatic cancer with no evidence of primary tumor. (from AJCC 7th Ed.)
Exocrine or endocrine pancreatic cancer with a finding of carcinoma in situ. This also includes the PanIn III classification. (from AJCC 7th Ed.)
Exocrine or endocrine pancreatic cancer with tumor limited to the pancreas, measuring 2 cm or less in greatest dimension.. (from AJCC 7th Ed.)
A second generation, small-molecule mimetic of ATP that targets the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. PKI-179 selectively inhibits mTOR and phosphoinositide-3-kinase (PI3K) alpha. By inhibiting the PI3K/mTOR signaling pathway, this agent may inhibit tumor cell proliferation and survival.
Exocrine or endocrine pancreatic cancer with tumor limited to the pancreas, measuring more than 2 cm in greatest dimension. (from AJCC 7th Ed.)
Exocrine or endocrine pancreatic cancer with tumor extending beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery. (from AJCC 7th Ed.)
Exocrine or endocrine pancreatic cancer with tumor involving the celiac axis or the superior mesenteric artery (unresectable primary tumor). (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of exocrine or endocrine pancreatic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to staging of regional lymph nodes.
Exocrine or endocrine pancreatic cancer in which the regional lymph nodes cannot be assessed. (from AJCC 7th Ed.)
Exocrine or endocrine pancreatic cancer with no regional lymph node metastasis. (from AJCC 7th Ed.)
Exocrine or endocrine pancreatic cancer with regional lymph node metastasis. (from AJCC 7th Ed.)
A pathologic finding about one or more characteristics of exocrine or endocrine pancreatic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases. There is no pathologic M0 for exocrine or endocrine pancreatic cancer. (from AJCC 7th Ed.)
Exocrine or endocrine pancreatic cancer with distant metastasis. (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of exocrine or endocrine pancreatic cancer, following the rules of the TNM AJCC v7 classification system. Information necessary for the clinical staging of pancreatic cancer can be obtained from physical examination and three dimensional radiographic imaging studies, which include triphasic, contrast-enhanced multislice computed tomography or magnetic resonance imaging (MRI). (from AJCC 7th Ed.)
A clinical finding about one or more characteristics of exocrine or endocrine pancreatic cancer, following the rules of the TNM AJCC v7 classification system as they pertain to distant metastases.
Exocrine or endocrine pancreatic cancer without evidence of distant metastasis. (from AJCC 7th Ed.)
A finding that indicates the specific type of abnormality that is present in a heart valve such as insufficiency, regurgitation or prolapse.
A term that refers to the staging of renal cell cancer according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of bladder cancer according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of vulvar carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of vaginal cancer according to the American Joint Committee on Cancer, 6th edition.
The mean value of the amount of weight gained over a period of time.
An electrocardiographic finding of P waves with two peaks longer in duration than normal and amplitude greater than normal. (CDISC)
The amount of weight gained over a period of time in relation to the total weight.
An indication that the subject was alive when taken out of the study.
An electrocardiographic finding of a change in heart rate that is associated with breathing.
The ability to move body parts and limbs without physical restriction.
The cessation of life at an unplanned time.
The state of consciousness is not controlled. The possibility exists for having multiple conscious states over a period of time.
A term that refers to the staging of cervical cancer according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of uterine corpus cancer according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of fallopian tube carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of esophageal carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of colorectal carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of colon carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of rectal carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of rectosigmoid carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of hepatocellular carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of gallbladder cancer according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of breast cancer according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of cutaneous melanoma, following the rules of the TNM AJCC v6 classification system.
A term that refers to the staging of lung carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of penile carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of prostate carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of nasopharyngeal carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of oropharyngeal carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of hypopharyngeal carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of pharyngeal carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of laryngeal carcinoma according to the American Joint Committee on Cancer, 6th edition.
A term that refers to the staging of nasal cavity and paranasal sinus carcinoma according to the American Joint Committee on Cancer, 6th edition.
A chimeric monoclonal antibody against human colorectal and pancreatic carcinoma-associated antigens (CPAAs) with potential immunomodulating and anti-tumor activities. Anti-CPAA monoclonal antibody NPC-1C binds to CPAAs, which may activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response and an antibody-dependent cellular cytotoxicity (ADCC) response against CPAA-expressing tumor cells. CPAAs, cell surface proteins, are upregulated on colon and pancreatic tumor cells. NPC-1C contains the variable region of the heavy and light chain of murine NPC-1 and linked in-frame to constant regions of a human IgG1 isotype.
A synthetic oligonucleotide containing phosphorothioate oligodeoxynucleotide with potential immunopotentiating activity. TLR9 agonist EMD 1201081 binds to and activates the intracellular Toll-like receptor (TLR) 9 in monocytes/macrophages, plasmacytoid dendritic cells (DCs) and B cells, initiating immune signaling pathways, activating B cells and inducing T-helper cell cytokine production. TLR9 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.
A formulation containing protein-stabilized liposome nanoparticles encapsulating the poorly water-soluble, second-generation taxane analog docetaxel with antineoplastic activity. Docetaxel binds to and stabilizes the beta-tubulin subunit, thereby inhibiting microtubule disassembly which results in cell-cycle arrest at the G2/M phase and cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and displays immunomodulatory and pro-inflammatory properties by inducing various mediators of the inflammatory response. Compared to the use of toxic carriers to increase solubilization of docetaxel, protein-stabilized liposomal docetaxel improves drug solubility while avoiding carrier-associated toxicity.
A metal complex compound of phthalocyanide with photosensitizing activity. Upon injection with photocyanide and subsequent introduction to photodynamic therapy (PDT), photocyanide becomes activated and forms reactive oxygen species that induce apoptosis.
Juice made form dark, purple grapes that contain polyphenols with antioxidant and potential cardiovascular protecting activities. Purple grape juice contains high amounts of flavonoids that may increase antioxidant activity and reduce oxidative stress, reduce low-density lipoprotein (LDL), and improve nitric oxide formation, endothelial function and vasodilation.
A plasmid encoding the protein antiangiogenic metargidin plasmid (AMEP), the disintegrin domain of ADAM-15 (metargidin), with potential antiangiogenic and antimetastatic activities. Upon intratumoral electrotransfer of plasmid encoding AMEP, AMEP binds to cellular integrin receptors alpha-v-beta-3 (avb3) and alpha-5-beta-1 (a5b1), which are upregulated on activated endothelial cells and a variety of tumor cells. Binding to the integrin receptors may inhibit angiogenesis and may inhibit tumor cell proliferation.
A cholesterol carbonate derivative of 4-demethylpenclomedine (DM-PEN) with potential antineoplastic alkylating activity. Upon intravenous administration of 4-demethylcholesteryloxycarbonylpenclomedine, the carbonium moiety binds to and alkylates DNA at the N7 guanine position, thereby causing DNA crosslinks. This prevents DNA replication, inhibits cellular proliferation and triggers apoptosis. In addition, due to its lipophilic cholesteryl moiety this agent is able to cross the blood brain barrier (BBB) and therefore can be given intravenously compared to other alkylating agents that need to be given intra-cranially.
An allogeneic tumor cell vaccine containing myeloma cancer cells transfected with the granulocyte macrophage-colony-stimulating factor (GM-CSF) gene with potential antineoplastic activity. Upon vaccination, allogeneic GM-CSF-based myeloma cellular vaccine secretes GM-CSF, which may potentiate a tumor-specific cytotoxic T-lymphocyte (CTL) response against myeloma cancer cell-associated antigens.
A cancer vaccine consisting of autologous dendritic cells (DCs) transduced with a recombinant adenovirus encoding p53 peptide, with potential immunomodulating activity. Intradermal vaccination with adenoviral-p53 transduced dendritic cell vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing mutant p53, resulting in tumor cell lysis. p53, a tumor suppressor gene, is mutated in many tumor cells, resulting in the loss of apoptosis regulation and abnormal cell proliferation.
A cancer cell-based vaccine containing liposome encapsulated melanoma antigens and an immunomodulatory factor, attached, via a metal chelator, to a dendritic cell receptor (DCR) ligand-containing a metal-affinity tag, with potential immunomodulating and antineoplastic activity. Upon intravenous administration of DCR ligand-bearing liposome-encapsulated melanoma antigens vaccine, the DCR ligand moiety of this vaccine targets receptors on dendritic cells (DCs), thereby presenting the antigens to DCs which may, in turn, stimulate the DCs and may activate the immune system to mount a cytotoxic T lymphocyte (CTL) response against melanoma cancer cell associated antigens.
An implant containing a sustained release particle of fluorouracil, an antimetabolite fluoropyrimidine analog of the nucleoside pyrimidine, with antineoplastic activity. Upon implantation and subsequent release, fluorouracil is converted into the active metabolite 5-fluoroxyuridine monophosphate that competes with the pyrimidine uracil during RNA synthesis while another active metabolite, 5-5-fluoro-2'-deoxyuridine-5'-O-monophosphate, inhibits thymidylate synthase and thus DNA synthesis.
A capsule containing a fermented soymilk extract and oligomeric proanthocyanidins (OPCs), green tea, spirullina, curcumin and antrodia camphorate powder, with potential antioxidant, immunomodulating, anti-infective and anti-cancer activities. OPCs/green tea/spirullina/curcumin/antrodia camphorate/fermented soymilk extract capsule may boost the immune system and may alleviate fatigue and poor appetite in cancer chemotherapy patients.
An immunoconjugate consisting of the recombinant form of the cytokine interleukin-2 (IL-2) fused to a human single-chain Fv (scFv) antibody fragment directed against the extra-domain B (ED-B) of fibronectin (L19), with potential immunopotentiating and antineoplastic activities. The L19 moiety of L19-IL2 monoclonal antibody-cytokine fusion protein binds to the ED-B domain of fibronectin on tumor cells in the tumor neovasculature. In turn, the IL-2 moiety may locally activate natural killer (NK) cells and macrophages, and may induce T cell cytotoxic immune responses against ED-B fibronectin-expressing tumor cells. This may specifically decrease the proliferation of ED-B-expressing tumor cells. ED-B is predominantly expressed during angiogenesis and tumor growth.
A peptide derived from human lactoferrin, with potential lytic and immunostimulating activities. Upon transdermal injection directly into the tumor, LTX315 may bind to the tumor cell membranes and subsequently lyse tumor cells, thereby inducing tumor cell necrosis. In turn, presentation of the tumor antigens to the immune system may induce systemic innate and adaptive immune responses mediated by anti-tumor natural killer (NK) cells, cytotoxic T lymphocytes, and natural killer T (NKT) cells. This may trigger an immune response against tumor associated antigens on tumors distant from the primary tumor. Human lactoferrin, a 692 amino acid glycoprotein, belongs to the transferrin family of metal-binding proteins.
A nutritional supplement containing a strain of the probiotic bacterium Lactobacillus plantarum 299v (Lp 299v) with potential antimicrobial, immune-boosting, and anti-inflammatory activities. Upon oral ingestion, L. plantarum strain 299v adheres to the intestinal mucosa, modulates the composition of the normal microflora, helps maintain adequate colonization of the gastrointestinal (GI) tract and improves digestion and metabolism. Upon colonization of the GI tract, the probiotic may form a protective barrier, thereby preventing attachment of pathogens, protecting against infections and boosting the immune system. In addition, Lp 299v stimulates the secretion of protective mucin and produces lactic acid and hydrogen peroxide as well as other substances, thereby creating an acidic environment which prevents growth of pathogens.
A nutritional supplement containing the probiotic bacterium Lactobacillus plantarum 299 (Lp 299) with potential antimicrobial, immune-boosting, and anti-inflammatory activities. Upon oral ingestion, Lp 299 adheres to the intestinal mucosa, modulates the composition of the normal microflora, helps maintain adequate colonization of the gastrointestinal (GI) tract and improves digestion and metabolism. Upon colonization of the GI tract, the probiotic may form a protective barrier, thereby preventing attachment of pathogens, protecting against infections and boosting the immune system. In addition, Lp 299 stimulates the secretion of protective mucin and produces lactic acid and hydrogen peroxide as well as other substances, thereby creating an acidic environment which prevents growth of pathogens.
An immunotoxin consisting of a monoclonal antibody directed against epithelial glycoprotein-2 (EP-2, or epithelial cell adhesion molecule (EpCAM)) conjugated to the bacterial toxin Pseudomonas exotoxin A (PE) with potential antineoplastic activity. Upon administration of anti-EGP-2 immunotoxin MOC31-PE, the monoclonal antibody moiety targets and binds to EP-2. Upon internalization, the Pseudomonas exotoxin A moiety then inactivates elongation factor 2 (EF-2) through ADP ribosylation, resulting in inhibition of protein synthesis in EP-2-expressing cells. EP-2, a tumor-associated antigen, is overexpressed in a variety of cancer cell types.
Autologous tumor cells transfected with a plasmid expressing recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) and bifunctional short hairpin RNA (bi-shRNA) against furin, with potential immunostimulatory and antineoplastic activities. Upon intradermal vaccination of bi-shRNA-furin/GM-CSF-expressing autologous tumor cell vaccine, expressed GM-CSF protein, a potent stimulator of the immune system, recruits immune effectors to the site of injection and promotes antigen presentation. The furin bifunctional shRNA blocks furin protein production. Decreased levels of furin lead to a reduction in the conversion of transforming growth factor (TGF) beta into TGF beta1 and beta2 protein isoforms. In turn, as part of the negative feedback mechanism, reduced furin protein levels inhibit TGFbeta1 and TGFbeta2 gene expression, thereby further decreasing TGF levels. As TGFs are potent immunosuppressive cytokines, reducing their levels may activate the immune system locally and this may eventually cause a cytotoxic T-lymphocyte (CTL) response against the tumor cells.
A multikinase inhibitor with potential antineoplastic activity. Multikinase inhibitor 4SC-203 selectively inhibits FMS-related tyrosine kinase 3 (FLT3/STK1), FLT3 mutated forms, and vascular endothelial growth factor receptors (VEGFRs). This may result in the inhibition of angiogenesis and cell proliferation in tumor cells in which these kinases are upregulated. FLT3 (FLK2), a class III tyrosine kinase receptor, is overexpressed or mutated in most B lineage and acute myeloid leukemias (AML). VEGFRs, tyrosine kinase receptors, are overexpressed in a variety of tumor cell types and play key roles in angiogenesis.
A plasmid vaccine encoding wild type human carcinoembryonic antigen (CEA) fused to a tetanus toxoid T helper epitope, with potential antineoplastic activity. Upon vaccination and subsequent intradermal electroporation, CEA/tetanus toxoid T helper epitope fusion protein-expressing DNA plasmid vaccine may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against CEA-expressing tumor cells. CEA, a tumor associated antigen, is overexpressed in a variety of cancer cell types. The tetanus toxoid helper peptide epitope, obtained from the bacterial Clostridium tetani toxoid, binds to class II MHC molecules and increases the helper T-cell response thereby inducing an increased and long-term immune response.
A synthetic water-soluble analogue of combretastatin A4, derived from the South African willow bush (Combretum caffrum), labeled with carbon C 14 with potential antineoplastic activity. The ombrabulin moiety of carbon C 14 ombrabulin binds to the colchicine binding site of endothelial cell tubulin, thereby inhibiting tubulin polymerization and inducing mitotic arrest and apoptosis in endothelial cells. As apoptotic endothelial cells detach from their substrata, tumor blood vessels collapse; the acute disruption of tumor blood flow may result in tumor necrosis. The radioisotope moiety of this agent acts as a radioactive tracer.
A small-molecule inhibitor of the human kinesin-related motor protein Eg5 with potential antineoplastic activity. Eg5 kinesin-related motor protein inhibitor 4SC-205 selectively inhibits the activity of Eg5, which may result in mitotic disruption, apoptosis and cell death. The ATP-dependent Eg5 kinesin-related motor protein (also known as KIF11 or kinesin spindle protein-5) is a plus-end directed kinesin motor protein essential for the regulation of spindle dynamics, including assembly and maintenance, during mitosis.
A cancer vaccine consisting of a replication-defective recombinant canarypox virus (ALVAC) encoding the cancer-testis antigen NY-ESO-1, with potential immunostimulatory and antineoplastic activities. Upon administration, ALVAC-ESO-1 vaccine may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against NY-ESO-1-expressing cancer cells, which may result in the inhibition of tumor cell proliferation. NY-ESO-1, a tumor associated antigen (TAA), is found in normal testis and on the surface of various tumor cells.
Human autologous peripheral blood lymphocytes (PBLs) transduced with a retroviral vector encoding a T cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1, with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo, and reintroduction into the patient, the NY-ESO-1 reactive TCR-transduced autologous PBLs bind to NY-ESO-1-overexpressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL) killing of NY-ESO-1-positive cancer cells. NY-ESO-1, a tumor associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types; the TCR is specific for NY-ESO-1:157-165.
A dendritic cell vaccine consisting of dendritic cells (DCs) electroporated with mRNA encoding three adjuvants, CD40 ligand (CD40L), a constitutively active TLR4, and CD70 (all together termed TriMix); coelectroporated with full-length mRNA encoding MAGE-A3, MAGE-C2, Tyrosinase and gp100; and linked to DC-LAMP, with potential immunostimulating activity. Upon vaccination, the DCs may stimulate the immune system to mount an antigen-specific cytotoxic T-lymphocyte (CTL) response against the melanoma antigens. This may decrease cellular proliferation of melanoma cells expressing these antigens. Electroporation with the adjuvants CD40L and TLR4 allows for the generation of mature and active DCs; electroporation with CD70 provides a costimulatory signal to CD27+ naive T cells thereby supporting T-cell proliferation and inhibiting T-cell apoptosis.
A gene therapy agent containing an attenuated, replication-competent, genetically engineered mutant form of the Herpes simplex virus 1 (HSV-1) strain KOS with potential antineoplastic activity. Upon infusion into the hepatic artery, oncolytic HSV-1 rRp450 replicates in hepatocellular carcinoma (HCC) cells and exerts direct cytotoxic effects eventually disrupting cancer cell membranes and liberating progeny virions thereby infecting adjacent tumor cells. In addition, rRp450 expresses the cytochrome P450 transgene that activates oxazaphosphorines, such as cyclophosphamide (CPA). Therefore, CPA can become activated in the presence of rRp450 and exert its antineoplastic effect. rRp450 is deleted for the HSV-1 gene UL39, encoding the viral ribonucleotide reductase large subunit infected cell protein 6 (ICP6), thereby disrupting the activity of viral ribonucleotide reductase and resulting in the inhibition of nucleotide metabolism and viral DNA synthesis in nondividing cells but not in dividing cells. UL39 is replaced by the rat CYP2B1 gene, encoding a cytochrome P450 enzyme that activates oxazaphosphorines. rRp450 also expresses viral thymidine kinase, which activates the cancer prodrug ganciclovir.
A cancer vaccine containing three HLA-A*2402-restricted peptide epitopes derived from cancer-testis antigens with potential immunostimulatory and antitumor activities. The peptide epitopes are derived from up-regulated lung cancer 10 (URLC10); cell division cycle associated 1 (CDCA1); and kinesin-like family member 20A (KIF20A). Upon administration, HLA-A*2402-restricted URLC10-CDCA1-KIF20A multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against URL10-, CDCA1-, and KIF20A-expressing tumor cells, resulting in tumor cell lysis and decreased tumor cell proliferation. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A cancer vaccine containing two HLA-A*2402-restricted peptide epitopes derived from cancer-testis antigens with potential immunostimulatory and antitumor activities. The peptide epitopes are derived from cell division associated 1 (CDCA1) and kinesin-like family member 20A (KIF20A). Upon administration, HLA-A*2402-restricted CDCA1-KIF20A multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against CDCA1- and KIF20A-expressing tumor cells, resulting in tumor cell lysis and decreased tumor cell proliferation. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with human leukocyte antigen (HLA)-A2-restricted melanoma-associated antigen peptides tyrosinase (TYR), MART-1(melanoma antigen recognized by T-cells) and melanoma antigen glycoprotein 100 (gp100), with potential immunomodulating and antineoplastic activity. Upon vaccination, HLA-A2-binding TYR/MART-1/gp100 multipeptide-pulsed autologous dendritic cell vaccine may stimulate the host immune system to mount an anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against Tyr-, MART-1 and gp100-expressing cancer cells, resulting in tumor cell lysis. HLA-A2 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A2 may improve antigenic peptide immunogenicity.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with human leukocyte antigen (HLA)-A1-binding melanoma-associated antigen peptides MAGE-1 and MAGE-3 with potential immunomodulating and antineoplastic activity. Upon vaccination, HLA-A1-binding MAGE-1/MAGE-3 multipeptide-pulsed autologous dendritic cell vaccine may stimulate the host immune system to mount an anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against MAGE1- and MAGE-3-expressing cancer cells, resulting in tumor cell lysis. HLA-A1 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A1 may improve antigenic peptide immunogenicity.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysate from autologous melanoma cells containing tumor associated antigens (TAAs) with potential immunostimulatory and antineoplastic activities. Upon administration, autologous melanoma lysate-pulsed autologous DC vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against melanoma cells, which may result in melanoma cell lysis.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysate from autologous melanoma cells containing tumor associated antigens (TAAs) and conjugated to the immunostimulant Keyhole limpet hemocyanin (KLH), with potential immunostimulatory and antineoplastic activities. Upon administration, autologous melanoma lysate/KLH-pulsed autologous dendritic cell vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against melanoma cells, which may result in melanoma cell lysis. KLH is an immunogenic carrier and serves as an immunostimulant to improve antigenic immune recognition and T-cell responses and can be used to evaluate vaccine efficacy.
An orally bioavailable inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity. XL019 inhibits the activation of JAK2 as well as the mutated form JAK2V617F, which may result in the inhibition of the JAK-STAT signaling pathway and may induce apoptosis. The JAK2 mutated form JAK2V617F has a valine-to-phenylalanine modification at position 617 and plays a key role in tumor cell proliferation and survival.
An orally bioavailable inhibitor of IAP (Inhibitor of Apoptosis Protein) family of proteins with potential apoptotic inducing and antineoplastic activity. IAP inhibitor AT-406 selectively inhibits the biological activity of IAP proteins, including X chromosome-linked IAP (XIAP), the cellular IAPs 1 (c-IAP1) and 2 (c-IAP2) and melanoma inhibitor of apoptosis protein (ML-IAP). This may restore and promote the induction of apoptosis through apoptotic signaling pathways. AT-406 may work synergistically with cytotoxic drugs to overcome tumor cell resistance to apoptosis. IAPs are overexpressed by many cancer cell types, suppressing apoptosis by binding and inhibiting active caspases-3, -7 and -9 via their BIR (baculoviral lAP repeat) domains.
A radioimmunoconjugate containing the recombinant humanized monoclonal antibody trastuzumab labeled with the radioisotope zirconium Zr 89 with radioisotopic activity and potential use as an imaging agent. The trastuzumab moiety of zirconium Zr 89 trastuzumab binds with high affinity to the extracellular domain of human epidermal growth factor receptor 2 (HER2). Upon binding, the radioisotope moiety may be detected using positron emission tomography (PET), thereby allowing the imaging and quantification of HER2-expressing tumor cells. HER2, a tyrosine kinase client protein of heat shock protein 90 (Hsp90), may be overexpressed on the cell surfaces of various tumor cell types.
A preparation of glucocorticoid receptor (GR) negative, allogeneic cytotoxic T-lymphocytes (CTLs) expressing a membrane-tethered interleukin 13 (IL13) cytokine chimeric T-cell antigen receptor (zetakine), with potential antineoplastic activity. Upon transfection of donor T-lymphocytes with a plasmid encoding a fusion protein of the IL13-zetakine and the selection-suicide expression enzyme HyTK, these modified CTLs are expanded and introduced into a patient with glioblastoma multiforme (GBM). This agent specifically targets IL13 receptor alpha2, a glioma-restricted cell-surface epitope; the CTLs exert their cytolytic effect thereby killing IL13Ra2-expressing glioma cells. In addition, IL13-zetakine redirected CTLs induce production of certain cytokines. Furthermore, due to the fact that these CTLs are GR negative, they can be used concomitantly with glucocorticoid therapy. The IL13-zetakine consists of an extracellular IL-13 E13Y mutein-human IgG4 hinge-Fc chimera fused to human cytoplasmic CD3-zeta via the transmembrane domain of human CD4.
A monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2) with potential immunomodulating and antineoplastic activity. After binding to HER2 on the tumor cell surface, anti-HER2 monoclonal antibody CT-P6 may induce a cytotoxic T-lymphocyte (CTL) as well as an antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells that overexpress HER2. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types.
A radiotracer containing paclitaxel labeled with the radioisotope fluorine F18 with potential use as an imaging agent. After cellular uptake, the paclitaxel moiety of fluorine F18 fluoropaclitaxel binds to tubulin. Upon uptake, the radioisotope moiety may be detected using positron emission tomography (PET), thereby allowing imaging and quantification of the biodistribution of paclitaxel. This could identify multidrug resistant (MDR) status of tumor cells and select patients that will likely respond to paclitaxel treatment.
An orally bioavailable non-steroidal androgen synthesis inhibitor of steroid 17alpha-monooxygenase (17,20 lyase) with potential antiandrogen activity. TAK-700 binds to and inhibits the steroid 17alpha-monooxygenase in both the testes and adrenal glands, thereby inhibiting androgen production. This may decrease androgen-dependent growth signaling and may inhibit cell proliferation of androgen-dependent tumor cells. The cytochrome P450 enzyme CYP17A1 (P450C17), localized to the endoplasmic reticulum (ER), exhibits both 17alpha-hydroxylase and 17,20-lyase activities, and plays a key role in the steroidogenic pathway that produces steroidal hormones, such as progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.
A recombinant fully human monoclonal antibody directed against the human A33 antigen, with potential immunomodulatory and antineoplastic activity. Anti-A33 monoclonal antibody KRN330 recognizes and binds to the human A33 antigen, which may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against A33-positive colorectal cancers. A33 antigen, a 43 kDa transmembrane glycoprotein of the immunoglobulin superfamily, is highly and homogenously expressed in 95% of colorectal cancer cancers with only restricted expression in normal colonic mucosa and small bowel epithelia.
An orally available capsule-based nutritional supplement containing indole-3-carbinol, calcium-D-glucarate, Schizandra, vitamin D3, milk thistle, stinging nettle and hydroxymatairesinol (HMR) lignans, with potential estrogen modulating, antiproliferative and antioxidant activity. Indole-3-carbinol, found in vegetables of the Cruciferae family, may inhibit mammary cell growth and exerts antiestrogenic activity; Milk thistle (Silybum marianum) and Schizandra chinensis may enhance some of the phase II detoxification enzymes; Calcium-D-glucarate and vitamin D3 may inhibit mammary cell growth; stinging nettle may exert its effect through its aromatase inhibiting activity; HMR lignans may have a beneficial effect on estrogen balance and levels. Therefore, ingredients in indole-3-carbinol/calcium/Schizandra/vitamin D3/milk thistle/stinging nettle/lignan-based nutritional capsule may alter estrogen balance and may protect against mammary carcinogenesis.
An orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A, with potential antimitotic and antineoplastic activity. Aurora A kinase inhibitor MK5108 binds to and inhibits Aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and eventually inhibition of cell division, proliferation and an induction of apoptosis in cells overexpressing Aurora A kinase. Aurora A kinase localizes to the spindle poles and to spindle microtubules during mitosis, and is thought to regulate spindle assembly. Aurora kinases are overexpressed in a wide variety of cancers.
An orally bioavailable inhibitor of signal transducer and activator of transcription 3 (STAT3), with potential antineoplastic activity. OPB-31121 inhibits the phosphorylation of STAT3, which prevents binding of STAT3 to DNA sequences on a variety of STAT3-responsive promoters and may result in the inhibition of STAT3-mediated transcription and, potentially, the inhibition of tumor cell proliferation. STAT3 is constitutively activated in a variety of cancers, contributing to the loss of cell growth control and neoplastic transformation.
An orally bioavailable, small molecule and dual kinase inhibitor of human epidermal growth factor receptors 1 (EGFR/ErbB1) and 2 (HER2/ErbB2), with potential antineoplastic activity. EGFR/HER2 kinase inhibitor TAK-285 binds to and inhibits EGFR and HER2, which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. This agent may be active against EGFR/HER2-expressing tumor cells that are resistant to trastuzumab. EGFR and HER2, receptor tyrosine kinases overexpressed in a variety of tumor cell types, play major roles in tumor cell proliferation and tumor vascularization. In addition, TAK-285 appears to pass the blood brain barrier (BBB) and does not appear to be a substrate for efflux pumps.
A selective small-molecule inhibitor of the proto-oncogene c-Met with potential antineoplastic activity. c-Met inhibitor MK2461 preferentially inhibits activated c-Met in an ATP-competitive manner, thereby inhibiting its tyrosine kinase activity, which may inhibit c-Met signaling and result in cell growth inhibition in tumors that overexpress c-Met. c-Met, encoding the hepatocyte growth factor receptor (HGFR) tyrosine kinase, plays an important role in tumor cell proliferation and has been shown to be overexpressed or mutated in a variety of cancers.
A sustained-release drug delivery embolization system containing small polymeric beads impregnated with the anthracycline antibiotic idarubicin with potential antineoplastic activity. The beads consist of polyvinyl alcohol (PVA) microspheres modified with sulfonic acid groups and loaded with idarubicin. During transarterial chemoembolization (TACE) in the hepatic artery, idarubicin-eluting beads embolize to the tumor vasculature, occlude tumor blood vessels and induce ischemic necrosis of tumor tissue due to mechanical blockage of the tumor vasculature. Simultaneously, idarubicin-eluting beads release cytotoxic idarubicin locally and in a sustained manner. This may result in idarubicin-mediated inhibition of tumor cell proliferation.
An indenoisoquinoline and non-camptothecin inhibitor of topoisomerase I (Top I) with potential antineoplastic activity. Topoisomerase I inhibitor LMP776 binds to the topoisomerase I-DNA covalent cleavage complexes, and inhibits repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations. Compared to camptothecins, indenoisoquinolines are chemically stable, produce stable Top I-DNA cleavage complexes, induce unique DNA cleavage sites and appear more resistant to multidrug efflux pumps.
A potent, selective and orally bioavailable, difluoropyrrolidine-based inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity.
The sodium salt form of lometrexol, a folate analogue antimetabolite with antineoplastic activity. As the stereoisomer of 5,10-dideazatetrahydrofolate, lometrexol selectively inhibits glycinamide ribonucleotide formyltransferase (GARFT), the enzyme that catalyzes the first step in the de novo purine biosynthetic pathway, thereby inhibiting DNA synthesis and leading to an inhibition of tumor cell proliferation. The agent has been shown to be active against tumors that are resistant to the folate antagonist methotrexate, but causes severe, dose-limiting toxicities.
An orally bioavailable agonist of the human beta-3 adrenergic receptor (ADRB3), with muscle relaxing, neuroprotective and potential antineoplastic activities. Upon oral administration, mirabegron binds to and activates ADRB3, which leads to smooth muscle relaxation. Mirabegron also restores sympathetic stimulation in mesenchymal stem cell (MSC) niches, inhibits JAK2-mutated hematopoietic stem cell (HSC) expansion and blocks the progression of myeloproliferative neoplasms (MPNs). Lack of sympathetic stimulation of the MSC and HSC niche is associated with the development of MPNs.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.)- 2003
A water-soluble prodrug of a pyridyl cyanoguanidine compound and an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT) with potential antineoplastic activity. Teglarinad is rapidly converted in the bloodstream into an active compound through hydrolytic cleavage of the carbonate ester bond. The activated form inhibits NAMPT, thereby inhibiting nicotinamide adenine dinucleotide (NAD+) biosynthesis and induces a rapid decline in intracellular NAD+ followed by ATP reduction. As NAD+ is essential for tumor cell growth, inhibition of NAMPT induces tumor cell death. NAMPT is an essential enzyme in the synthesis of NAD+ and is upregulated in some cancers.
A novel helicase-primase inhibitor that is active against varicella-zoster virus and herpes simplex virus types 1 and 2. Amenamenir stabilizes the interaction between the helicase-primase and its DNA substrates, preventing the progression through helicase or primase catalytic cycles, thus interfering with viral DNA replication and viral growth.
An acyclic guanosine analog with activity against varicella zoster virus (VZV) and other members of the herpesvirus family. Omaciclovir is selectively phosphorylated by viral thymidine kinase to its monophosphate form and is further modified to a triphosphate, which is an inhibitor of VZV DNA polymerase.
A second generation, quinoxaline non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against human immunodeficiency virus 1 (HIV-1). Talviraline inhibits both HIV-1 induced cell killing and viral replication.
A dihydrochloride salt form of valtorcitabine, a prodrug form of torcitabine (L-deoxycytidine), a nucleoside analog with activity against hepatitis B virus. Torcitabine is modified in vivo to its triphosphate form and acts as a competitive inhibitor of viral DNA polymerase.
A benzenesulfonamide-based diuretic. Ambuside is structurally similar to thiazide type diuretics and acts in a similar manner.
A recombinant form of activated human blood coagulation factor VII that promotes hemostasis by activating the extrinsic pathway of the coagulation cascade.
A platinum-based compound with alkylating activity. Eptaplatin induces pt-DNA adducts and DNA crosslinks, thereby resulting in an inhibition of cellular proliferation.
A radiopharmaceutical containing flutemetamol, a thioflavin derivative of Pittsburgh compound B (PiB) labeled with the radioisotope fluorine F18 that can be used to detect beta-amyloid deposition upon positron emission tomography (PET). After intravenous administration of flutemetamol F 18, the flutemetamol moiety selectively accumulates in and binds to cerebral fibrillar amyloid-beta in the brain. The fluorine F18 radioisotope moiety is detected using PET, which allows imaging and quantification of amyloid-beta density. Amyloid plaque deposition is linked to cognitive decline, including Alzheimer's disease, and may be linked to chemotherapy-induced cognitive impairment (CICI).
An orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Tanexaban is extensively metabolized in the liver to its active metabolite and is excreted by the kidneys and in the feces.
A nitrofuran derivative with antibacterial activity.
A selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor with antihyperglycemic activity.
The anhydrous form of canagliflozin, a C-glucoside with a thiophene ring that is an orally available inhibitor of sodium-glucose transporter 2 (SGLT2) with antihyperglycemic activity. Canagliflozin is also able to reduce body weight and has a low risk for hypoglycemia.
A sulfonamide derivative with antihyperglycemic activity. Like sulfonylureas, gliamilide is able to lower blood glucose levels by increasing the release of insulin from pancreatic beta cells.
A thiadiazine derivative with hypoglycemic activity. Like sulfonylureas, tifenazoxide binds to ATP-sensitive inwardly-rectifier potassium Kir6.2/SUR1 (IKATP) channels on the membrane of pancreatic beta cells and stimulates insulin release to reduce blood glucose levels.
A derivative of the cholesterol absorption inhibitor ezetimibe designed to be non-soluble and target the luminal surface of the GI tract. In Phase II trials canosimibe reduced LDL cholesterol levels, but it did not demonstrate the desired efficacy in a Phase III study, and was discontinued.
A nanoparticle formulation containing N-glutaryl phosphatidylethanolamine (NGPE)-liposomes encapsulating oxaliplatin and conjugated to the human transferrin (Tf) ligand, with potential antineoplastic activity. Upon infusion of oxaliplatin-encapsulated transferrin-conjugated NGPE liposomes, the transferrin moiety targets and binds to the Tf receptor, which is overexpressed on a variety of human cancer cells. Upon binding and internalization, oxaliplatin is released and its active derivatives alkylate macromolecules, forming both inter- and intra-strand platinum-DNA crosslinks, which results in an inhibition of DNA replication and transcription. By extending the circulation time and specifically targeting transferrin receptors, this formulation may improve the efficacy and safety of oxaliplatin therapy, compared to administration of oxaliplatin alone. NGPE, a reactive phospholipid, is used as a linker to attach the Tf ligand, to the liposome.
A cancer vaccine consisting of a recombinant modified vaccinia Ankara (MVA) viral vector encoding the gene for the CD4 epitope-rich C-terminal domain of the Epstein Barr Virus (EBV) antigen EBNA1 and fused to the full-length of the EBV-associated antigen latent membrane protein 2 (LMP2), with potential immunostimulatory and antineoplastic activities. Upon administration, MVA EBNA1/LMP2 vaccine may elicit a cytotoxic T-cell immune response against cancer cells expressing EBNA1 and LMP2. Multi-antigen vaccine therapy may be more efficacious than single-antigen therapy vaccine therapy. EBNA1, a sequence-specific DNA binding protein, plays an important role in EBV episomal genome maintenance and gene transactivation.
A lipid-based multi-peptide cancer vaccine targeted against multiple cancers with immunopotentiating activity. Therapeutic breast/ovarian/prostate peptide cancer vaccine DPX-0907 is a lyophilized liposomal proprietary preparation comprised of 7 tumor-specific HLA-A2-restricted epitopes (TAAs): Topoisomerase II alpha, B-cell receptor-associated protein 31 (CDM protein), TNF-alpha-converting enzyme (TACE/ADAM17), Abelson homolog 2 (Abl2), gamma catenin (Junction plakoglobin), epithelial discoidin domain receptor 1 (EDDR1) and integrin beta 8 subunit. Upon vaccination, the lyophilized antigen/adjuvant/liposome complex is re-suspended in Montanide 1SA51 VG to create a depot effect, thereby presenting the TAAs to the immune system for a prolonged period of time. This may stimulate a potent cytotoxic T-lymphocyte (CTL) immune response against cancer cells that express these 7 TAAs and share epitopes with the vaccine epitope peptides, resulting in tumor cell lysis. The 7 TAAs are overexpressed on the surface of breast/ovarian and prostate cancer cells and play an important role in tumor cell growth and survival.
An orally bioavailable second mitochondrial-derived activator of caspases (SMAC) mimetic and inhibitor of IAP (Inhibitor of Apoptosis Protein) family of proteins, with potential antineoplastic activity. SMAC mimetic LCL161 binds to IAPs, such as X chromosome-linked IAP (XIAP) and cellular IAPs 1 and 2. Since IAPs shield cancer cells from the apoptosis process, this agent may restore and promote the induction of apoptosis through apoptotic signaling pathways in cancer cells. IAPs are overexpressed by many cancer cell types and suppress apoptosis by binding and inhibiting active caspases-3, -7 and -9, which play essential roles in apoptosis (programmed cell death), necrosis and inflammation.
A small-molecule inhibitor of the mitotic kinesin centromere-associated protein E (CENP-E), with potential antineoplastic activity. Upon administration, GSK-923295 binds to and inhibits CENP-E, thereby preventing cell division, inducing cell cycle arrest, and ultimately leading to an inhibition of cell proliferation. CENP-E, a kinetochore-associated mitotic kinesin, plays an essential role in chromosome movement during mitosis and regulates cell-cycle transition from metaphase to anaphase.
An ATP-competitive inhibitor of the serine/threonine kinases Aurora B and C with potential antineoplastic activity. Aurora B/C kinase inhibitor GSK1070916A binds to and inhibits the activity of Aurora B and C, which may result in inhibition of cellular division and a decrease in the proliferation of tumor cells that overexpress the Aurora kinases B and C. Aurora kinases play essential roles in mitotic checkpoint control during mitosis, and are overexpressed by a wide variety of cancer cell types.
A 0.1% topical formulation of uracil used potentially to lower the incidence of hand-foot syndrome (HFS) (or palmar-plantar erythrodysesthesia) during 5-fluorouracil (5-FU) or 5-FU prodrug capecitabine chemotherapy. Upon local administration of uracil ointment to the skin, uracil competes with capecitabine or 5-FU as substrates for the activating enzyme thymidine phosphorylase and the metabolizing enzyme dihydropyrimidine dehydrogenase. This may prevent the production of 5-FU as well as the breakdown of 5-FU into the toxic metabolites locally. As the 5-FU metabolites are responsible for the presentation of HFS, inhibiting their formation may prevent this adverse effect. By applying a high concentration of uracil locally, the skin toxicities of 5-FU may be countered while preserving the systemic anti-cancer activity of the 5FU.
A parenteral iron solution containing ferric iron complexed with carboxymaltose polymers, used in parenteral iron-replacement therapy. Upon administration, ferric carboxymaltose is removed from plasma by the reticuloendothelial system. Subsequently, ferric iron binds to transferrin or is stored as ferritin. Transferrin-bound iron is transported in the plasma to the liver, spleen and bone marrow, where it is incorporated into hemoglobin, and to muscle, where it is incorporated into myoglobin.
A heat-treated varicella-zoster virus (VZV) vaccine with potential immunomodulating activity. Upon vaccination with heat-treated varicella-zoster virus vaccine V212, this vaccine may activate the immune system to generate specific anti-VZV antibodies and an active immunity against VZV infection.
An immunoconjugate consisting of milatuzumab, a humanized monoclonal antibody against CD74, conjugated to the anthracycline antibiotic doxorubicin with potential antineoplastic activity. The milatuzumab moiety of this ADC selectively binds to CD74 on tumor cell surfaces; upon internalization, the doxorubicin moiety is released, where it intercalates between base pairs in the DNA helix and inhibits topoisomerase II, thereby preventing DNA replication and increasing double-strand breakage. As a result, this agent may inhibit the proliferation of cancer cells that overexpress CD74. CD74, an integral membrane protein and tumor associated antigen (TAA), is overexpressed in certain cancer cells and promotes survival in rapidly proliferating tumor cells.
A polymeric nanoparticle (PNP) formulation containing the taxane docetaxel, a semi-synthetic analogue of paclitaxel, with antineoplastic activity. Docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which results in cell-cycle arrest at the G2/M phase, preventing cell proliferation. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response. Compared to docetaxel alone, the PNP formulation may enhance stability and improve delivery.
A preparation of interleukin 21 (IL-21) stimulated, CD8+ T-lymphocytes sensitized to MART-1 (melanoma antigen recognized by T-cells) antigen with potential immunostimulating and antineoplastic activities. CD8+ T-lymphocytes are exposed ex vivo to autologous dendritic cells (DCs) pulsed with MART-1 antigen peptide and grown in the presence of IL-21. These tumor-reactive T-cells may stimulate a host immune response against tumor cells expressing the MART-1 antigen, resulting in tumor cell lysis. MART-1 is expressed by certain types of melanoma cells. IL-21, a cytokine involved in the regulation of cellular immune responses, may play a key role during priming of antigen-specific CD8+ T cells and may enhance proliferation of the CTLs.
An orally bioavailable small-molecule Smoothened (Smo) antagonist with potential antineoplastic activity. Smoothened antagonist LEQ506 selectively binds to the Hedgehog (Hh)-ligand cell surface receptor Smo, which may result in the suppression of the Hh signaling pathway, thereby inhibiting tumor cell growth. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair. Dysregulated activation of Hh pathway signaling and uncontrolled cellular proliferation, as is observed in a variety of cancers, may be associated with mutations in the Hh-ligand cell surface receptor Smo.
The orotate salt form of carboxyamidotriazole (CAI), an orally bioavailable small molecule with potential antiangiogenic and antiproliferative activities. Carboxyamidotriazole binds to and inhibits non-voltage-operated calcium channels, blocking both Ca2+ influx into cells and Ca2+ release from intracellular stores, resulting in the disruption of calcium channel-mediated signal transduction. CAI inhibits PI3 activity and vascular endothelial growth factor (VEGF) signaling. This may inhibit endothelial proliferation, tumor cell growth, invasion and metastasis.
Autologous human cytomegalovirus (CMV)-specific human cytotoxic T-lymphocytes (CTLs) transduced with a retroviral vector encoding a human anti-Her-2 (epidermal growth factor receptor 2) chimeric T cell receptor (CAR) gene with potential immunostimulatory and antineoplastic activities. Autologous CTLs from a patient with Her-2- and CMV-positive glioblastoma multiforme (GBM) are genetically modified to express CAR gene specific for Her-2 on their cell surfaces. After expansion in culture and reintroduction into the patient, the anti-HER2-CAR autologous CMV-specific CTLs bind to Her-2 antigen on tumor cell surfaces; subsequently, Her-2-positive tumor cells and stem cells may be lysed. Her-2 (ErbB-2), a receptor tyrosine kinase (RTK) overexpressed by a variety of cancer cell types, plays key roles in tumor cell proliferation and tumor angiogenesis. CMV is present in the majority of GBM tumors.
An orally bioavailable inhibitor of CXC chemokine receptor 4 (CXCR4) with receptor binding and hematopoietic stem cell-mobilization activities. CXCR4 inhibitor POL6326 binds to the chemokine receptor CXCR4, thereby preventing the binding of stromal derived factor-1 (SDF-1 or CXCL12) to the CXCR4 receptor and subsequent receptor activation. This may induce the mobilization of hematopoietic stem and progenitor cells from the bone marrow into blood. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types; CXCL12/CXCR4 interaction induces retention of hematopoietic cells in the bone marrow.
A population of allogeneic cytotoxic T lymphocytes (CTLs) specifically reactive to the herpes virus cytomegalovirus (CMV) with potential immunomodulating and antiviral activities. Upon immunoprophylactic adoptive cell therapy infusion with allogeneic cytomegalovirus-specific cytotoxic T lymphocytes, these CTLs may help reconstitute CMV-specific CTL responses in CMV-infected immunocompromised hosts after allogeneic hematopoietic stem cell transplant, thereby potentially preventing the occurrence of CMV viral disease or reducing the amount of antiviral drug therapy.
An orally available, genetically engineered Salmonella typhimurium strain expressing a truncated form of the human cytokine interleukin-2 (IL-2) gene, with antitumor activity. Upon administration of recombinant attenuated S. typhimurium expressing IL-2 (SalpIL2), this Salmonella strain may selectively accumulate and divide in a variety of tumor types, and express IL-2. In turn, IL-2 may induce natural killer (NK) cell proliferation thereby enhancing their activity. This may inhibit the growth of tumor cells.
An inhibitor of the receptor tyrosine kinase Met (hepatocyte growth factor receptor) with potential antineoplastic activity. MET inhibitor EMD 1204831 selectively binds to Met tyrosine kinase, thereby disrupting MET mediated signal transduction pathways. This may induce cell death in tumor cells overexpressing this kinase. MET is overexpressed or mutated in many tumor cell types, and plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis.
An orally bioavailable, small molecule inhibitor of vascular endothelial growth factor (VEGF) synthesis with potential antiangiogenesis and antineoplastic activities. VEGF inhibitor PTC299 targets post-transcriptionally by selectively binding the 5'- and 3'-untranslated regions (UTR) of VEGF messenger RNA (mRNA), thereby preventing translation of VEGF. This inhibits VEGF protein production and decreases its levels in the tumor and bloodstream. In turn, this may result in the inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and eventually the induction of tumor cell death. VEGFs are upregulated in a variety of tumor cell types and play key roles during angiogenesis. In addition, PTC299 may enhance the antitumor activity of other chemotherapeutic agents.
A term that refers to the staging of renal cell cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of bladder cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of vulvar carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of vaginal cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of cervical cancer according to the American Joint Committee on Cancer, 7th edition.
A subjective answer of partial agreement.
A term that refers to the staging of uterine corpus cancer (carcinoma or carcinosarcoma) according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of fallopian tube carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of esophageal carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of gastric carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of colorectal carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of colon carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of rectal carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of rectosigmoid carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of hepatocellular carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of gallbladder cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of breast cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of cutaneous melanoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of lung carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of prostate carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of penile carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of nasopharyngeal carcinoma according to the American Joint Committee on Cancer, 7th edition.
On most occasions, or in most situations.
A term that refers to the staging of oropharyngeal carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of hypopharyngeal carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of pharyngeal carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of nasal cavity and paranasal sinus carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of laryngeal carcinoma according to the American Joint Committee on Cancer, 7th edition.
A replication-defective, E1- and E2b-deleted oncolytic adenoviral serotype 5 (Ad5) encoding an epitope of human carcinoembryonic antigen (CEA) with potential antineoplastic activity. Adenoviral vector Ad5-CEA(6D) vaccine expresses a highly immunogenic analogue of CEA [CAP1-(6D)]. Upon administration, this vaccine may induce both humoral and cellular immune responses against tumor cells expressing the CEA antigen, thereby resulting in the immune-mediated inhibition of tumor cell proliferation and tumor cell death. CEA, a tumor-associated antigen, is overexpressed in various tumor cell types. Deletion of early genes E1 and E2b in Ad5 potentially circumvent pre-existing anti-adenovirus immunity and is capable of inducing strong immune responses.
A population of cytotoxic T-lymphocytes (CTLs) that are therapeutically administered to a recipient individual who is genetically distinct from a donor of the same species.
An aqueous suspension of the olamine salt form of ciclopirox, a synthetic, broad-spectrum hydroxypyridone antifungal agent with additional antibacterial and anti-inflammatory activities. Although the exact mechanism of action of ciclopirox has yet to be fully elucidated, this agent is able to chelate trivalent cations, such as Fe3+, thereby inhibiting the availability of essential co-factors for enzymes. This may lead to a loss of activity of enzymes that are essential for cellular metabolism, organization of cell wall structure and other crucial cell functions. In addition, ciclopirox exerts its anti-inflammatory activity by inhibiting 5-lipoxygenase and cyclooxygenase (COX).
A pegylated, proprietary lipocalin that targets human vascular endothelial growth factor (VEGF), with potential antineoplastic activity. Pegylated anti-VEGF anticalin PRS-050 specifically targets and binds to VEGF receptor 2 (VEGFR2 or KDR), thereby preventing its activity. This may inhibit angiogenesis and eventually reduce tumor cell growth.
A trivalent cancer vaccine containing the ganglioside lactones GM2, GD2 and GD3 conjugated with the immunostimulant keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. Vaccination with GM2 lactone/GD2 lactone/GD3 lactone-KLH conjugate trivalent vaccine may elicit antibodies against tumor cells expressing any of these epitopes, resulting in an antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells expressing these gangliosides. GM2, GD2 and GD3 are tumor associated antigens (TAAs) that are overexpressed in a variety of tumor cell membranes.
A cell-based cancer vaccine comprised of autologous dendritic cells pulsed with four alpha-fetoprotein (AFP) peptides, with potential immunostimulatory and antineoplastic activities. Upon administration, AFP peptide-pulsed autologous dendritic cell vaccine may stimulate anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against AFP-expressing cancer cells, resulting in tumor cell lysis. AFP is overexpressed in a variety of cancer cells.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with corpses of apoptotic leukemic cells, with potential immunostimulatory and antineoplastic activities. Upon vaccination, autologous dendritic cells pulsed with leukemic apoptotic corpse may activate the immune system to mount an anti-tumoral cytotoxic T-lymphocyte (CTL) response against leukemic cells expressing leukemia-associated antigens, which may result in leukemic cell lysis and inhibition of tumor cell growth. Apoptotic tumor cell corpses contain an array of tumor associated antigens (TAAs).
A proprietary DNA-based cancer vaccine that encodes a melanoma antigen tyrosinase-related protein 2 (TRP2) cytotoxic T-lymphocyte (CTL) epitope and a modified monoclonal antibody, a chimera of human IgG1/murine IgG2a with T cell mimotopes expressed within the complementarity-determining regions (CDR) of the antibodies, with potential immunostimulating and antineoplastic activities. Upon intramuscular injection and electroporation, melanoma TRP2 CTL epitope vaccine SCIB1 expresses the modified antibody. Subsequently, the Fc component of the engineered antibody targets and binds to the CD64 receptor on the dendritic cells (DCs); upon processing by DCs, the cellular immune system may be activated to induce helper T-cell and CTL immune responses against tumor cells expressing the TRP2 antigen.
A mixture of two recombinant IgG1 antibodies directed against different epitopes in the epidermal growth factor receptor (EGFR) extracellular domain III, with potential antineoplastic activity. Anti-EGFR monoclonal antibody mixture Sym004 binds to the extracellular domain of EGFR, thereby preventing ligand binding. This may prevent activation and subsequent dimerization of the receptor; the decrease in receptor activation may result in an inhibition of downstream ERK and JNK signaling pathways and thus inhibition of EGFR-dependent tumor cell proliferation and metastasis. In addition, binding of Sym004 to EGFRs causes EGFR internalization and degradation. EGFR, a receptor tyrosine kinase, often is overexpressed on the cell surfaces of various solid tumor cell types.
A fully human monoclonal antibody against RON (recepteur d'origine nantais; macrophage stimulating 1 receptor), with potential antineoplastic activity. Anti-RON monoclonal antibody IMC-RON8 binds to RON, thereby preventing binding of its ligand hepatocyte growth factor-like protein (HGFL or macrophage-stimulating protein (MSP)). This may prevent RON receptor-mediated signaling and may prevent cellular proliferation in tumor cells overexpressing RON. RON, a receptor tyrosine kinase, is overexpressed in a variety of epithelial cancer cell types and plays an important role in cellular proliferation, migration and invasion.
A human IgM monoclonal antibody directed against disialoganglioside GD2 with potential immunomodulating activity. Upon administration, anti-GD2 monoclonal antibody MORAb-028 may stimulate the immune system to exert a complement-mediated cytotoxic response against GD2-expressing tumor cells. The glycosphingolipid GD2 is a tumor associated antigen (TAA) overexpressed on the surface of many cancer cells.
A monoclonal antibody directed against the melanosomal membrane protein gp75 (or Tyrosinase-Related Protein 1 (TRP1)) with potential immunostimulatory and antineoplastic activities. Anti-gp75 monoclonal antibody IMC-20D7S targets and binds to gp75. This may lead to the induction of cytotoxic T cell immune and antibody-mediated immune responses against melanoma cells expressing gp75. gp75, a pigmentation-associated antigen, is expressed in melanosomes of human melanocytes and melanomas.
A humanized IgG1 monoclonal antibody directed against the placenta growth factor (PGF), with potential anti-angiogenic and antineoplastic activities. Anti-PGF monoclonal antibody RO5323441 binds to both PGF-1 and -2, thereby inhibiting the binding of PGF-1 and -2 to the vascular endothelial growth factor receptor-1 (VEGFR-1) and subsequent VEGFR-1 phosphorylation. This may result in the inhibition of tumor angiogenesis and tumor cell proliferation. PGF, a member of the VEGF sub-family and a key molecule in angiogenesis and vasculogenesis, is upregulated in many cancers.
An inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential chemo- and/or radiosensitizing activity. PARP inhibitor E7016 selectively binds to PARP and prevents PARP mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks and promotes genomic instability and eventually leads to apoptosis. In addition, this agent may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapy and radiation therapy. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks.
An orally bioavailable proteasome inhibitor with potential antineoplastic activity. Proteasome inhibitor ONX 0912 inhibits the activity of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome; this may result in an accumulation of unwanted or misfolded proteins. Disruption of various cell signaling pathways may follow, eventually leading to the induction of apoptosis and inhibition of tumor growth. Proteasomes are large protease complexes that degrade unneeded or damaged proteins that have been ubiquitinated.
An iodine 131 radioimmunoconjugate of a small immunoprotein (SIP), derived from the variable region fragment of human monoclonal antibody L19, that is directed against the extra-domain B (ED-B) of fibronectin, with potential radioimmunotherapeutic activity. The SIP moiety of iodine I 131 anti-fibronectin antibody fragment L19-SIP binds to the ED-B domain of fibronectin on tumor cells in the tumor neovasculature. Upon internalization, the I 131 radionuclide may selectively detect or deliver cytotoxic radiation to fibronectin-expressing tumor cells. ED-B of fibronectin, a naturally occurring marker of tissue remodeling and angiogenesis, is expressed in the majority of aggressive solid human tumors, whereas it is not detectable in normal vessels and tissues.
A rhenium (Re) 188 conjugate of ethiodized oil (lipiodol), an iodinated ethyl ester derived from poppy seed oil, with potential antineoplastic activity. Upon hepatic intra-arterial injection rhenium Re 188 ethiodized oil accumulates in hepatocellular carcinoma (HCC) tumor cells, thereby delivering a cytotoxic dose of radiation through Re 188 directly to the tumor cells. This may kill tumor cells while sparing surrounding normal cells and tissues. Compared to iodine I 131, Re 188 has a shorter half-life.
A derivative of the amino acid histidine labeled with heavy hydrogen (D) used in diagnostic procedures. Upon intake of deuterated 3-methylhistidine (3-MH), this agent is incorporated into muscle protein and then is subsequently excreted unchanged in the urine. By measuring the amount of 3-MH in the urine, via analysis of deuterium, the rate of protein muscle catabolism can be determined and the risk of skeletal muscle atrophy or cachexia can be assessed. 3-methylhistidine is a myofibrillar-specific amino acid and is mainly found in muscle myosin and actin; proteolysis of myofibrils releases 3-MH that is excreted unchanged in the urine.
An orally available inhibitor of p70S6K signaling, with potential antineoplastic activity. p70S6K inhibitor LY2584702 inhibits ribosomal protein S6 Kinase (p70S6K), and prevents phosphorylation of the S6 subunit of ribosomes, thereby inhibiting normal ribosomal function within tumor cells leading to a decrease in protein synthesis and in cellular proliferation. P70S6K, a serine/threonine kinase, acts downstream of PIP3 and phosphoinositide-dependent kinase-1 in the PI3 kinase pathway, is often upregulated in a variety of cancer cells, and is involved in the regulation of cell growth, proliferation, motility, and survival.
An orally bioavailable inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity. JAK2 inhibitor AZD1480 inhibits JAK2 activation, leading to the inhibition of the JAK/STAT (signal transducer and activator of transcription) signaling including activation of STAT3. This may lead to induction of tumor cell apoptosis and a decrease in cellular proliferation. JAK2, often upregulated or mutated in a variety of cancer cells, mediates STAT3 activation and plays a key role in tumor cell proliferation and survival.
An immunocytokine of the human monoclonal antibody fragment F16 (scFv) against the extra-domain A1 of tenascin-C fused, via a short 5-amino acid linker, to a recombinant form of the human cytokine interleukin-2 (IL-2) with potential immunostimulating and antineoplastic activities. The monoclonal antibody portion of the F16-IL2 fusion protein binds to tumor cells expressing the tumor associated antigen (TAA) tenascin-C. In turn, the IL-2 moiety of the fusion protein stimulates natural killer (NK) cells, macrophages and neutrophils and induces T-cell antitumor cellular immune responses thereby selectively killing tenascin-C-expressing tumor cells. In addition, F16-IL2 may potentiate the cytotoxicity of other chemotherapeutic agents. Tenascin-C, a glycoprotein of the extracellular matrix, is expressed in many cancer cell types.
An error in medication preparation or administration attributed to software.
Event in which data (charting, orders, results) is not correctly stored, transferred, updated, or displayed.
Event in which data is accessed by the healthcare provider and either the wrong patient or the wrong data is retrieved despite correct inquiry procedures.
The chemical reactions and pathways involving alpha-linolenic acid, an unsaturated omega-6 fatty acid that has the molecular formula C18H32O2. [CHEBI:32387]
A series of molecular signals initiated by the binding of a neurotrophin to a receptor on the surface of a target cell, and ending with regulation of a downstream cellular process, e.g. transcription. Neurotrophins are a family of secreted growth factors that induce the survival, development, and function of neurons. [GOC:bf, GOC:jc, GOC:signaling, PMID:17466268, PR:000021998, Wikipedia:Neurotrophin]
Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortic peptides. MC1R activates the cyclic AMP (cAMP) response-element binding protein (CREB). Increased expression of MITF and its activation by phosphorylation (P) stimulate the transcription of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT), which produce melanin. Melanin synthesis takes place within specialized intracellular organelles named melanosomes. Melanin-containing melanosomes then move from the perinuclear region to the dendrite tips and are transferred to keratinocytes by a still not well-characterized mechanism.
Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR.
p53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated genes. This results in three major outputs; cell cycle arrest, cellular senescence or apoptosis. Other p53-regulated gene functions communicate with adjacent cells, repair the damaged DNA or set up positive and negative feedback loops that enhance or attenuate the functions of the p53 protein and integrate these stress responses with other signal transduction pathways.
Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains more than 20 members in mammals and plays a pivotal role in the recognition of intracellular ligands. NOD1 and NOD2, two prototypic NLRs, sense the cytosolic presence of the bacterial peptidoglycan fragments that escaped from endosomal compartments, driving the activation of NF-kappa-B and MAPK, cytokine production and apoptosis. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. These NLRs include NALP1, NALP3 and Ipaf. The inflammasomes are critical for generating mature proinflammatory cytokines in concert with Toll-like receptor signaling pathway.
A series of molecular signals initiated by binding of a ligand to a member of the ERBB family of receptor tyrosine kinases on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription. [GOC:jc, PMID:16460914, PR:000001812, Wikipedia:ErbB]
Wnt proteins are secreted morphogens that are required for basic developmental processes, such as cell-fate specification, progenitor-cell proliferation and the control of asymmetric cell division, in many different species and organs. There are at least three different Wnt pathways: the canonical pathway, the planar cell polarity (PCP) pathway and the Wnt/Ca2+ pathway. In the canonical Wnt pathway, the major effect of Wnt ligand binding to its receptor is the stabilization of cytoplasmic beta-catenin through inhibition of the bea-catenin degradation complex. Beta-catenin is then free to enter the nucleus and activate Wnt-regulated genes through its interaction with TCF (T-cell factor) family transcription factors and concomitant recruitment of coactivators. Planar cell polarity (PCP) signaling leads to the activation of the small GTPases RHOA (RAS homologue gene-family member A) and RAC1, which activate the stress kinase JNK (Jun N-terminal kinase) and ROCK (RHO-associated coiled-coil-containing protein kinase 1) and leads to remodelling of the cytoskeleton and changes in cell adhesion and motility. WNT-Ca2+ signalling is mediated through G proteins and phospholipases and leads to transient increases in cytoplasmic free calcium that subsequently activate the kinase PKC (protein kinase C) and CAMKII (calcium calmodulin mediated kinase II) and the phosphatase calcineurin.
A series of molecular signals initiated by binding of a ligand to a ERBB3 receptor on the surface of a cell, followed by transmission of the signal by a heterodimeric complex of ERBB2 and ERBB3. ERBB2, which does not bind any known ligand, is activated through formation of a heterodimer with another ligand-activated ERBB family member such as ERBB3. ERBB3 also has impaired kinase activity and relies on ERBB2 for activation and signal transmission. [GOC:signaling, PMID:16460914, Reactome:REACT_115761.1]
A series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor ERBB4 on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription. [GOC:jc, PMID:16460914, PR:000007160, Reactome:REACT_115596.2]
A series of molecular signals initiated by the binding of a ligand to a beta-type platelet-derived growth factor receptor (PDGFbeta) on the surface of a signal-receiving cell, and ending with regulation of a downstream cellular process, e.g. transcription. [GOC:bf, GOC:signaling, GOC:yaf, PMID:10372961, PR:000002035]
Any process that modulates the frequency, rate or extent of androgen receptor activity. [GOC:obol]
A series of molecular signals initiated by the sphingolipid sphingosine-1-phosphate (S1P) binding to a receptor on the surface of the cell, and which proceeds with the activated receptor transmitting the signal by promoting the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The pathway ends with regulation of a downstream cellular process, e.g. transcription. [GOC:ascb_2009, GOC:signaling, PMID:22001186, Reactome:REACT_18416.2]
A series of molecular signals that starts with the binding of stem cell factor to the tyrosine kinase receptor KIT on the surface of a cell, and ends with regulation of a downstream cellular process, e.g. transcription. Stem cell factor (KIT ligand) binding to the receptor Kit mediates receptor dimerization, activation of its intrinsic tyrosine kinase activity and autophosphorylation. The activated receptor then phosphorylates various substrates, thereby activating distinct signaling cascades within the cell that trigger a change in state or activity of the cell. [GOC:nhn, GOC:signaling, PMID:16129412]
Any series of molecular signals initiated by the binding of an extracellular ligand to a vascular endothelial growth factor receptor-1 (VEGFR-1) located on the surface of the receiving cell, and ending with regulation of a downstream cellular process, e.g. transcription. [GOC:bf, GOC:uh, PR:000007563, Wikipedia:FLT1, Wikipedia:VEGF_receptors]
Any series of molecular signals initiated by the binding of an extracellular ligand to a vascular endothelial growth factor receptor-3 (VEGFR-3) located on the surface of the receiving cell, and ending with regulation of a downstream cellular process, e.g. transcription. [GOC:bf, GOC:uh, PR:000007565, Wikipedia:VEGF_receptors, Wikipedia:VEGFR3]
A radioconjugate consisting of 6-fluorodopamine labeled with fluorine F18 (6-[18F]FDA), with potential diagnostic activity. Upon administration, 6-[18F]FDA is taken up by presynaptic sympathetic nerve endings via the norepinephrine transporter (NET) uptake-1. Once inside, 6-[18F]FDA is rapidly converted by dopamine-beta-hydroxylase into 6-[18F]fluoronorepinephrine (6-[18F]FNE) and stored into neuronal storage vesicles. Upon positron emission tomographic (PET) scanning of the F18, sympathetic innervated regions can be visualized, such as those in pheochromocytoma.
An octapeptide (amino acids 136-143) derived from the proteolytic enzyme urokinase plasminogen activator (uPA), with potential antineoplastic activity. A6 is derived from the nonreceptor-binding domain and connecting region of urokinase. Administration of A6 inhibits the interaction of uPA with its receptor uPAR, and may inhibit endothelial cell motility and tumor cell invasion. uPA and uPAR promote extracellular matrix degradation and growth factor activation and correlate positively with angiogenesis, cancer cell invasion and metastasis.
An agarose matrix containing mouse renal adenocarcinoma (RENCA) cells, with potential antineoplastic activity. The agarose-agarose macrobeads consist of two spherical agarose layers; the mouse RENCA cells are contained within the inner agarose layer. Upon placement into the abdominal cavity, the restricted mouse renal adenocarcinoma cells in the agarose macrobeads produce and release certain growth-retarding factors that inhibit the proliferation of the RENCA cells; Upon diffusion of these growth-slowing factors out of the agarose layers, these substances may inhibit cancer cell proliferation of proliferating tumors.
An immunotherapeutic containing a proprietary adjuvant system combined with a melanoma-associated antigen peptide MAGE-A3 epitope with potential immunomodulating and antineoplastic activities. Intramuscular administration with GSK1572932A may stimulate the immune system to exert both humoral and cellular immune responses against MAGE-A3-expressing tumor cells. MAGE-A3, a tumor associated antigen (TAA), is overexpressed in a variety of tumor cell types, including non-small cell lung cancer (NSCLC), melanoma, head and neck cancer, and bladder cancer.
A vaccine consisting of detoxified tetanus toxoid, detoxified diphtheria toxoid, acellular pertussis antigens, inactivated poliovirus (IPV) types 1,2 and 3 and hepatitis B (HBV) surface antigen, with active immunizing activities against diphtheria, tetanus, pertussis, hepatitis B, and poliomyelitis. The acellular pertussis components in this vaccine, produced by Bordetella pertussis, are detoxified pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN). Upon intramuscular injection, this vaccine activates the immune system to develop antibodies against tetanus toxin, diphtheria toxin, B. pertussis antigens, polioviruses and HBV. The diphtheria and tetanus toxoids and pertussis antigens (inactivated PT, FHA, and pertactin) are adsorbed onto aluminum hydroxide; the hepatitis B antigen is adsorbed onto aluminum phosphate.
A vaccine containing detoxified tetanus toxoid and detoxified diphtheria toxoid adsorbed on aluminum phosphate with active immunizing activity against diphtheria and tetanus. Intramuscular injection with this vaccine activates the immune system to develop antibodies against tetanus toxin and diphtheria toxin.
A vaccine containing HER2/Neu-derived epitope (amino acids 776-790) linked to li-Key peptide (li-Key/HER2/neu hybrid peptide or AE37), and combined with granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential antineoplastic and immunoadjuvant activities. Upon vaccination, AE37 may activate the immune system and stimulate T-helper cells against HER2/Neu expressing cancer cells. GM-CSF may potentiate the immune response against cancer cells expressing the HER2/Neu antigen. The Ii-Key moiety, a 4-amino acid (LRMK) epitope from the MHC class II-associated invariant chain (Ii protein), increases T-helper cell stimulation against HER2/neu antigen when compared to unmodified class II epitopes. HER2/neu, a tumor associated antigen (TAA), is overexpressed in a variety of tumor cell types and is highly immunogenic.
A vaccine containing a HER2/Neu-derived epitope (amino acids 654-662) (GP2), and combined with granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential antineoplastic and immunoadjuvant activity. Upon vaccination, GP2 may activate the immune system to mount a cytotoxic T-lymphocyte (CTL) immune response against HER2/Neu expressing cancer cells. GM-CSF may potentiate a tumor-specific cytotoxic T-lymphocyte (CTL) response against cancer cells expressing the HER2/Neu antigen. HER2/neu, a tumor associated antigen (TAA), is overexpressed in a variety of tumor cell types and is highly immunogenic.
An emulsion of 4 melanoma peptides with potential immunomodulating and antineoplastic activities. Upon vaccination, 4-peptide melanoma vaccine may stimulate an immune response against 4 different melanoma associated antigens. This may lead to a reduction in tumor cell proliferation of cancer cells expressing these antigens.
An agent that inhibits P-cadherin (cdh3), with potential antineoplastic activity. PF-03732010 binds to and inhibits the activity of p-cadherin. Inhibition of the activity of p-cadherin may inhibit tumor cell invasion and proliferation in p-cadherin expressing tumor cells. P-cadherin, a cell-surface protein and member of the cadherin family, is overexpressed in a variety of solid tumors, and plays a role in cell adhesion, motility, invasion and proliferation.
An MDM2 (human homolog of double minutes-2; HDM2) antagonist with potential antineoplastic activity. RO5045337 binds to MDM2, thereby preventing the binding of the MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this MDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored, which may result in the restoration of p53 signaling and thus the p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger protein, is a negative regulator of the p53 pathway; often overexpressed in cancer cells, it has been implicated in cancer cell proliferation and survival.
A purified, natural saponin isolated from the soapbark tree Quillaja saponaria Molina with potential immunoadjuvant activity. When co-administered with a vaccine, OBI-821 may increase antibody and cytotoxic T-lymphocyte (CTL) responses against the vaccine's targeted antigen(s).
A human IgG4 monoclonal antibody against B-cell activating factor (BAFF), with potential immunomodulating and antineoplastic activities. Tabalumab binds to and inhibits the activity of both soluble and cell surface-bound BAFF. This may reduce the activity, proliferation and survival of B-cells. A dysregulated expression of BAFF, a member of the tumor necrosis factor (TNF) family of proteins, is often seen in certain autoimmune diseases and certain cancers, and may promote B lymphocyte activation, proliferation and survival.
A human IgG1 monoclonal antibody directed against neuropilin-1 (NRP1), with potential antiangiogenic and antineoplastic activities. Upon intravenous administration, MNRP1685A specifically targets and binds to NRP1; the antibody-NRP1 complex prevents the subsequent coupling of NRP1 to VEGFR2, thereby potentially inhibiting VEGF-mediated signaling and potentially preventing angiogenesis. In combination with other anti-VEGF therapies, MNRP1685A may enhance their anti-angiogenic effect. NRP1 is a membrane-bound co-receptor normally expressed by endothelial cells and overexpressed by certain tumor cells, and plays a role in angiogenesis, cell survival, migration, and invasion.
An orally available agent targeting phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR kinase inhibitor GDC-0980 inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated in a PI3K-independent fashion.
A liposomal formulation containing the antisense oligodeoxynucleotide (ODN) growth factor receptor-bound protein 2 (Grb2), with potential antineoplastic activity. Upon administration, liposome-incorporated Grb2 antisense oligodeoxynucleotide binds directly to and blocks Grb2 mRNA, thereby preventing Grb2 protein synthesis, leading to inhibition of cell proliferation of cancer cells overexpressing Grb2. Grb2, an adaptor protein involved in growth signaling pathways, is upregulated in certain tumor cells.
A technetium Tc 99m radiopharmaceutical of a glutamate-rich peptide (GP) conjugated, via carbodiimide linker, to the heparin-like polysaccharide chitosan (CH) in a 1:1 ratio, with potential tumor targeting property. Upon administration, 99m Tc-glycopeptide targets and is taken up by glutamate-specific transporters on tumor cells. Upon internalization, the Tc99m moiety can be visualized upon scanning. GP may potentially be used as a drug carrier for antineoplastic drug delivery to tumor cells.
Exosomes loaded with non-small cell lung cancer (NSCLC)-specific antigens, with potential immunostimulating and antineoplastic activities. Exosomes derived from autologous maturing dendritic cells (DCs) are pulsed with HLA-DP04-restricted MAGE-3, and HLA-A02-restricted peptides NY-ESO-1, MAGE-1, MAGE-3, and MART-1. Upon vaccination, these exosomes may stimulate natural killer (NK) cell activation and proliferation, restoration of NKG2D expression on NK cells, and antigen-specific T-cell responses. This may eventually lead to inhibition of tumor cell proliferation in NSCLC expressing these specific tumor antigens. These exosomes, nanovesicles secreted from DCs, are embedded with molecules necessary for potent immune responses on the exosomal surface, such as MHC class II molecules, CD40, ICAM-1, IL-15Ralpha, and NKG2D ligands.
An extract of the flesh from the fruit of Phaleria macrocarpa, an Indonesian herbal medicine, with potential antineoplastic activity. Although the active ingredients and exact components are unclear, gallic acid and its derivatives in DLBS-1425 appear to inhibit the phosphoinositide-3 kinase (PI3K)/protein kinase B (AKT) signaling pathway by reducing PI3K transcription followed by a reduction in AKT phosphorylation. This extract also appears to induce apoptosis through induction of pro-apoptotic genes such as BAX, BAD and PUMA and inhibition of the apoptosis suppressor Bcl-2.
Stage I includes: IA: (T1, N0, M0); IB: (T2, N0, M0). T1: Tumor invades lamina propria or muscle layer. T1a: Tumor invades lamina propria. T1b: Tumor invades muscle layer. N0: No regional metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage II includes: IIA: (T3, N0, M0); IIB: (T1, N0, M0); (T2, N0, M0); (T3, N0, M0). T2: Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, or pancreas, omentum or extrahepatic bile ducts. (AJCC 6th ed.) - 2003
Stage III includes: (T4, Any N, M0). T4: Tumor invades main portal vein or hepatic artery or invades multiple extrahepatic organs or structures. (AJCC 6th ed.) - 2003
The tetrasodium salt of a synthetic analogue of the lipid A portion of the endotoxin lipopolysaccharide (LPS) with potential immunomodulating activity. Eritoran binds to the Toll-like receptor (TLR)/CD14/MD2 receptor complex present on most cells of the immune system, inhibiting the activation of the receptor complex by LPS, which may result in the inhibition of pro-inflammatory cytokine secretion and a potentially fatal systemic inflammatory response syndrome (SIRS). LPS is found in the outer membrane of Gram-negative bacteria and binds to the TLR/CD14/MD2 receptor complex of immune cells, especially macrophages, resulting in the release of pro-inflammatory cytokines.
A conclusion has yet to be established as the investigation is incomplete.
Problems traced to the design specifications (e.g. in the requirements, testing processes, hazard analysis, implementation strategy).
Device problems including set-up, operation, and disassembly of equipment.
An existing condition or disease is demonstrably responsible for the adverse event and use of the device has neither caused nor otherwise influenced this condition/disease-related adverse event.
Problems traced to the user not following the manufacturer's instructions.
The undesirable presence of living organisms such as bacteria, fungi, or viruses or their products (enzymes or toxins).
Reported adverse event known and documented in the labeling (including both short or long term known complications or adverse reactions).
Problems that occur as the result of problems with the labeling (including package inserts, instruction manuals, instructions for use).
Problems traced to improper routine or preventative maintenance.
Problems traced to manufacturing process.
A defect in the processes or systems used in the manufacture of the device. Examples include problems within the change control, production, or quality control processes.
Problems traced to the intentional use of the device in an unapproved procedure, for an unapproved patient, or for which it is contraindicated, or not listed on the label.
Problems traced to the use of the device more than once when it is designed for only one use.
The device complaint or problem cannot be confirmed.
The interaction between the user and device, or sample, caused or contributed to the error. This includes unintended inappropriate use of the device and incorrect sample preparation.
Problems that occurred because the device was assembled incorrectly.
The device causes cellular or tissue responses that elicit an undesirable local or systemic effect in the recipient or beneficiary of that therapy. (See ISO 10993)
The device's ability to trigger development of cancer.
Devices that do not send or receive adequate signals (this speaks to the interoperability between devices).
The device affects the body's ability to activate the complement system of the immune system, thereby interfering with the ability to clear pathogens. This may be caused by an interaction of the device with chemicals or materials.
Problems related to electromagnetic interference (EMI) by physical contact with conductors (e.g. wires, resistors, terminals) as opposed to radiated EMI which is caused by induction (without physical contact of the conductors).
Problems due to change control or incorrect version, including regional requirements.
Data was lost or corrupted during the operation of reducing storage space or communication bandwidth.
Problems caused by changes in the shape or size of the device due to an applied force. This can be a result of tensile forces, compressive forces, shear, bending, tensile (pulling), or torsion.
Problems that occur when the device becomes worn, weakened, corroded, or broken down due to processes such as aging, permeation, and corrosion.
The device had faulty (incomplete or incorrect) software design.
A device that experienced problems due to ingress, or coating, of dust or dirt.
Problems related to leakage currents which may cause electric shock. These currents usually flow through the protective ground conductor. In its absence, these currents could flow from the device to the ground via the human body.
Device-to-device or device-environment problem resulting from electromagnetic disturbances.
Problems due to sudden and momentary bursts of electrical current flowing between two objects at different electrical potentials.
Problems traced to the device reaching the end of its useful life.
The undesirable presence of toxins associated with certain bacteria (e.g. gram negative bacteria).
Problems related to the energy storage system (e.g. the rechargeable battery, charging system, or capacitor) and includes problems such as premature power source depletion and battery explosions.
Problems that occurred due to factors within the environment e.g. dust, dirt, humidity, temperature.
Problems due to the weakening or breakdown of its material when subjected to stress or a series of repeated stresses.
Problems caused by the separation of a component, object, or material into two or more pieces including shear.
Problems caused by its surface coming in contact with another surface or fluid.
The device's ability to cause damage to genetic material (e.g. leading to malignant tumors).
Problems that result from the gradient-induced fields generated during radiologic procedures e.g. magnetic resonance imaging.
Problems that results from improper sequential activation of components.
The device affects or impacts the blood or its components. (See ISO 10993 all parts)
Device performance was affected by the humidity, or changes in humidity, of the environment in which it was used.
The unacceptable distortion of an image due to signal loss that may occur during a radiologic procedure such as magnetic resonance imaging.
Problems due to insufficient or excessive resistance to current flow either by the device or circuit.
Problems associated with the improper combination of materials or elements present in the device (e.g. improper composition of the materials of a capacitor).
Problems that occur due to the presence of a material that should not be present or part of the device.
A device that malfunctions due to a component(s)/accessory that does not operate correctly and according to the device's specifications.
A device that malfunctions because it was incorrectly installed, set-up, or configured (e.g. misconfiguration of an ""automatic"" defibrillator to ""semi-automatic"", thereby leading to failure).
Problems due to inadequate or incorrect electrical insulation material.
The device software was found to contain errors in the user interface (including usability problems) or the interfaces with other systems.
Problems with the mechanical, electrical, or communication interface between two or more separate devices.
Insufficient, inadequate, or incorrect information provided on a device's label or documentation regarding e.g. its intended use, directions for use, and characteristics of the device, including its maintenance.
A device that experienced problems due to a loss in the power supply.
Problems that occurred because of the presence of either too much or too little lubricant where required (e.g. connectors, leading to failure mechanisms such as corrosion).
Problems due to unintended or excessive movement created by the application of magnetic fields.
A device malfunction or problem that occurs after production because the device was not properly maintained according to the instructions (e.g. maintenance may be performed by user facility, distributor, or service provider).
Problems with a device that can be traced to a problem in the manufacturing and/or production process.
The undesirable presence of pyrogens or fever-producing organisms caused by materials that permeate through the device.
Problems with the device materials or how its materials react to other elements either within the device or within the environment.
Problems that result from internal or external forces including fluids, other objects, or environmental or physiologic influences.
Problems caused by the sudden violent blow or collision to the whole device (e.g. by dropping).
The undesirable presence of microorganisms or microbes such as bacteria and fungi (yeasts and molds).
The device's ability to change genetic information (usually DNA) of an organism and thus increasing the frequency of mutations.
The device either functioned as intended or a problem was not found.
Use when no investigation can be performed and therefore no results will be obtained.
The device software contained software errors that did not impact its operation.
Problem due to an electrical circuit that does not conduct current because a switch is open, a wire is broken, etc.
Problems that occur during the performance, use, or functioning of the device.
Problems with the device's ability to pass light energy.
Problems that occurred because of a compromised packaging of the device (e.g. broken or incomplete seal).
Problems that occurred because of the device packaging.
The device affects the body's ability to activate platelet formation.
The device failed due to fluctuations within the power supply (e.g. transient power, power spike, power dip, or power sequencing).
Problems related to the source that provides electrical power to the device.
Problems related to the system(s) designed to prevent or warn about unsafe operation of the device.
Problems traced to the failure to maintain or establish techniques for controlling and verifying the product specifications (including materials used) identified by the manufacturer himself.
Problems due to unintended radiofrequency-induced temperature increase that can occur in the vicinity of the device.
Problems due to radiofrequency interference. RFI is a disturbance that affects an electrical circuit due to either electromagnetic conduction or electromagnetic radiation emitted from an external source.
Problems that occur with devices used for radiographic or imaging procedures e.g. CT scanners, magnetic resonance imaging.
Problems that occur due to the reactivity of materials (e.g. over-react or under-react).
The device affects reproductive function, embryo development (teratogenicity), and prenatal and early postnatal development. (ISO 10993 part 3)
Problems traced to how the device was transported e.g. temperature of shipping compartment or method of transportation.
Problems due to an unintentionally low-resistance connection between two points in an electric circuit, resulting in either excessive current flow that often causes damage or in a new shorter circuit that draws current away from the original pathways and components.
Problems due to the loss or weakening of an electrical signal or signals.
The device software was not installed as per the specifications or failed to properly install.
The software requirements for the device are either incomplete, inadequate, or in conflict.
The device software failed during operation as a result of a coding error.
The device software failed to provide adequate authorization, access control, protection and accountability features.
Problems that results from the incorrect sequencing or activation of software modules.
Problems that occurred when its material is either too flexible/pliable or inflexible/rigid when in contact by an applied force.
Problems that result from storing the device in an uncontrolled or improper environment (e.g. moisture sensitive devices stored in a humid environment).
Problems caused by either excessive or inadequate physical force exerted on it by another object resulting in problems e.g. wear, bending, deformation, fracture, fatigue.
Problems related to the presence of an inappropriate molecular geometry somewhere in the device (i.e. the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together).
Problems related to the temperature of the device.
The device causes the formation of blood clots in or along blood vessels resulting in disturbed or disrupted blood flow.
Problems that result from a combination of specification variances of the components.
Problems due to the premature or expected erosion of its material by use, deterioration, or change.
Communications problems between devices within a wired system.
Communications problems between devices within a wireless system.
Problems related to the incorrect or inadequate arrangement of the parts, components, elements, or materials.
Device performance was affected by the temperature, or changes in temperature, of the environment in which it was used.
Problems related to immunity or capabilities to resist electromagnetic interference (EMI).
Missing, incorrect, or inappropriate information on the labels e.g. mislabeled contents or device labeling characteristics or package contents
Inadequate information on the labels or in the instructions for use e.g. steps that are difficult to follow or that are missing.
Problems that occur due to the incompatibility of materials that co-exist simultaneously as part of the device.
The device software was found to contain errors in specifying or manipulating data items.
The device software was found to implement an incorrect sequence of steps for a specific computation.
Investigation is ongoing and results are not yet available. Do not use this code if the investigation is complete.
The hydrochloride salt form of cefozopran, a semi-synthetic, broad-spectrum, fourth-generation cephalosporin with antibacterial activity.
A lotion preparation of the olamine salt of ciclopirox, a synthetic hydroxypyridone derivative with broad-spectrum antifungal and anti-inflammatory activities. Although its mechanism of action is not well understood, ciclopirox may chelate trivalent cations, such as Fe3+ and Al3+, thereby inhibiting the availability of essential metal co-factors for enzymes, which may result in a loss of enzyme activities that are essential for cellular metabolism, organization of cell wall structure, and other crucial cell functions in a wide variety of fungal species. This agent may also disrupt DNA repair, cell division signals and mitotic spindles as well as some elements of intracellular transport in susceptible fungi. Ciclopirox exhibits anti-inflammatory activity by inhibiting 5-lipoxygenase and cyclooxygenase (COX).
A somatic mutation of the epidermal growth factor receptor gene which encodes a constitutively active 170kDa transmembrane protein, a short transmembrane region, and an intracellular domain.
A benign tubular adenoma with Sertoli cell differentiation.
A composite pheochromocytoma that is confined to the adrenal gland and does not have any metastatic potential.
A malignant epithelial neoplasm arising from the pars intermedia of the anterior pituitary gland.
An adrenal gland composite pheochromocytoma that metastasizes to other anatomic sites.
A malignant peripheral nerve sheath tumor that affects the esophageal wall.
A very rare benign neoplasm of mesothelial origin that arises from the pericardium.
A finding indicating that the extent of organ/tissue involvement by a malignant neoplasm is not reported or not assessed.
An electrocardiographic finding in which there are two R waves, which are two deflections above the baseline resulting from a single ventricular depolarization. The first upward deflection in the complex is the R wave. The S is the first downward deflection. A second upward deflection is called the R-prime wave.
An electrocardiographic finding in which the QT interval corrected for heart rate using Bazett's formula is slightly prolonged. Thresholds for different age, gender, and patient populations exist. (CDISC)
An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula is slightly prolonged. Thresholds for different age, gender, and patient populations exist. (CDISC)
An electrocardiographic finding in which there is evidence that electrical transmission through the left ventricle is impaired. (CDISC)
An electrocardiographic finding in which both the atrial and ventricular rhythm are controlled by an electrical impulse from an artificial cardiac pacemaker. (CDISC)
An electrocardiographic finding in which there is evidence that electrical transmission through the right ventricle is impaired with a maximal QRS duration of 110 ms and which does not meet the criteria for Incomplete Right Bundle Branch Block. (CDISC)
A benign or malignant lesion that arises within the bronchial wall.
The occurrence of multiple and independent glioblastomas that are unrelated to inherited neoplastic syndromes.
A rare, WHO grade II or III infiltrating astrocytoma characterized by the presence of sharply demarcated foci, composed of a neuropil-like matrix.
A morphologic finding indicating the presence of foci of neuropil-like matrix that are immunostained positive for synaptophysin in infiltrating astrocytomas.
A morphologic finding indicating the presence of neoplastic cells that display ependymal cell features.
A WHO grade I, indolent and relatively circumscribed brain tumor. Morphologically it is characterized by the presence of astrocytes that line vascular and hyalinized pseudopapillae. In between the pseudopapillae aggregates of neurocytes, large neurons, and ganglioid cells are present.
A WHO grade II neoplasm that arises from the brain parenchyma. Morphologically it is characterized by the presence of neoplastic uniform, round cells with neuronal differentiation. Unlike central neurocytoma, it does not involve the lateral ventricles. It usually affects young adults and has a favorable prognosis.
An orally active and small molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Hsp90 inhibitor Debio 0932 specifically blocks Hsp90, thereby inhibiting its chaperone function and promoting the degradation of its client proteins, many of which are oncogenic signaling proteins involved in tumor cell proliferation and survival. This may lead to an inhibition of tumor cell proliferation. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stabilization and degradation of many oncogenic signaling proteins.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with the prostate-specific tumor associated antigens (TAAs) prostate specific antigen (PSA) and prostate acid phosphatase (PAP), and conjugated to the immunostimulant Keyhole limpet hemocyanin (KLH), with potential immunostimulatory and antineoplastic activities. Upon administration, prostate cancer antigen/KLH-pulsed autologous dendritic cell vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against prostate cancer cells expressing PSA and PAP, which may result in prostate cancer cell lysis. KLH is an immunogenic carrier and serves as an immunostimulant to improve antigenic immune recognition and T-cell responses and can be used to evaluate vaccine efficacy.
An orally available inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. mTOR kinase inhibitor CC-223 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, plays an important role downstream in the PI3K/AKT/mTOR signaling pathway, which is frequently dysregulated in human cancers.
A deoxycytidine analog and high-affinity substrate for deoxycytidine kinase (DCK), labeled with fluorine F 18, with potential diagnostic activity upon positron emission tomography (PET) imaging. [18F]L-FAC is preferentially taken up by and accumulated in cells with high deoxycytidine kinase (DCK) levels, such as in tumor cells with dysregulated nucleoside metabolism. Upon uptake through the nucleoside transporter, [18F]L-FAC is phosphorylated by DCK and, subsequently, the 18F moiety can be visualized upon PET imaging. As many nucleoside analog prodrugs are chemotherapeutic agents that require DCK for activation, [18F]L-FAC can potentially be used as a marker to predict chemotherapeutic efficacy of these prodrugs. In addition, as DCK is upregulated in certain immune cells, such as activated T-cells, [18F]L-FAC can also be used to measure immune activation in response to immunomodulating agents. DCK, a rate-limiting enzyme in the nucleoside salvage pathway for DNA synthesis, is overexpressed in certain solid tumors, lymphoid and myeloid malignancies and certain immune cells, such as proliferating T-lymphocytes.
A human monoclonal antibody targeting connective tissue growth factor (CTGF) with potential anti-fibrotic and antineoplastic activities. FG-3019 binds to CTGF thereby preventing the binding of the ligand to the receptor and subsequent receptor activation. As CTGF enhances the production of collagen and fibronectin, FG-319 may prevent and reverse fibrosis. In addition, FG-3019 may prevent tumor cell proliferation in CTGF-expressing tumor cells. CTGF, a member of the CCN family (CTGF, CYR61/CEF and NOV), is expressed in a variety of tumor cell types and is involved in processes such as cell proliferation, cell migration, cell adhesion, differentiation and angiogenesis.
An injectable radiopharmaceutical formulation containing human serum albumin (HSA) microspheres labeled with Technetium-99m (Tc-99m) with diagnostic imaging activity. Technetium Tc 99m-labeled albumin microspheres contain the gamma-emitting Tc99m, a metastable nuclide of molybdenum-99. Upon injection into the hepatic artery, the radionuclide portion allows for SPECT (Single Photon Emission Computed Tomography) imaging of distribution patterns of the albumin microspheres. This may possibly predict the distribution of other agents with similar particle sizes within the liver and may give a prediction of the tumor response upon administration of such agents.
A formulation of the poorly soluble, semi-synthetic, second-generation taxane docetaxel encapsulated within liposomes, with antineoplastic activity. Upon intravenous administration, docetaxel binds to and stabilizes tubulin, thereby inhibiting microtubule disassembly which results in cell-cycle arrest at the G2/M phase and cell death. This liposomal formulation solubilizes docetaxel without the use of toxic solvents such as Tween 80, permitting the administration of larger doses of docetaxel while avoiding solvent-associated toxicity, including hypersensitivity reactions. In addition, liposomal delivery of docetaxel improves drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic drug effects while lowering the toxicity profile.
A formulation containing recombinant endostatin attached to polyethylene glycol (PEG), with potential anti-angiogenic and antineoplastic activities. Endostatin, a 20 kDa C-terminal proteolytic fragment of collagen XVIII, induces microvascular endothelial cell apoptosis and inhibits endothelial proliferation and angiogenesis, which may result in a reduction of tumor cell growth. Modification with PEG extends the circulation half-life of endostatin, improves stability and increases solubility in organic solvents.
Genetically-modified neural stem cells (NSCs) transfected with the Escherichia coli (E. coli) suicidal gene cytosine deaminase (CD), with potential antineoplastic adjuvant activity. Upon intracerebral injection, E. coli CD-expressing genetically modified NSCs express the E. coli cytosine deaminase, an enzyme that catalyzes the intracellular conversion of the nontoxic prodrug 5-fluorocytosine (5-FC) into the cytotoxic 5-fluorouracil (5-FU). Co-administration of this agent with 5-FC and upon local activation of 5-FU in the brain tumor, 5-FU disrupts DNA synthesis in tumor cells thereby impeding cellular proliferation with minimal systemic exposure and toxicity.
A recombinant form of the human PRAME (Preferentially Expressed Antigen of Melanoma) protein combined with the AS15 adjuvant, with potential immunostimulatory and antineoplastic activities. Upon intramuscular administration, GSK2302025A may stimulate the host immune response to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells that overexpress the PRAME protein, resulting in tumor cell lysis. The tumor-associated antigen PRAME is often overexpressed by a variety of tumor cell types. AS15 is an potent adjuvant liposomal formulation that contains CpG 7909, monophosphoryl lipid, and QS-21.
An orally available, Polo-like kinase 1 (PLK1) inhibitor with potential antineoplastic activity. Polo-like kinase 1 inhibitor TAK-960 selectively inhibits PLK1, inducing selective G2/M cell-cycle arrest followed by apoptosis in a variety of tumor cells while causing reversible cell-cycle arrest at the G1 and G2 stages without apoptosis in normal cells. PLK1 inhibition may result in the inhibition of proliferation in PLK1-overexpressed tumor cells. PLK1, named after the polo gene of Drosophila melanogaster, is a serine/threonine kinase crucial in the regulation of mitosis.
A liposomal formulation of the 24-mer oligonucleotide PNT100, with potential antineoplastic activity. PNT2258 targets and complements to untranscribed DNA sequence upstream of BCL2 promoters, thereby interfering with DNA replication and transcription of the BCL2 gene. This may promote and restore the apoptotic pathway in BCL2-overexpressing tumor cells. BCL2, an anti-apoptotic protein, is overexpressed in a wide variety of tumors.
An antibody drug conjugate (ADC) containing the fully human IgG2k monoclonal antibody targeting an epitope of SLC44A4 (AGS-5) linked, via a valine-citrulline (vc) maleimidocaproyl (mc) linker, to the antimicrotubulin drug monomethyl auristatin E (MMAE), with potential antineoplastic activity. The monoclonal antibody moiety of ASG-5ME selectively binds to AGS-5. After internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and tumor cell apoptosis. SLC44A4, potentially a sodium-dependent transmembrane transport protein, is overexpressed on more than 80 percent of samples derived from patients with pancreatic, prostate and gastric cancers.
An orally available small-molecule inhibitor of mutant (V600E) v-raf murine sarcoma viral oncogene homolog B1 (BRAF) with potential antineoplastic activity. BRAF(V600E) kinase inhibitor RO5212054 selectively binds to the ATP-binding site of BRAF(V600E) kinase and inhibits its activity, which may result in an inhibition of an over-activated MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. The valine to glutamic acid substitution at residue 600 accounts for about 90% of BRAF gene mutations; the oncogenic product, BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the MAPK signaling pathway. The BRAF(V600E) mutation has been found to occur in approximately 60% of melanomas, and in about 8% of all solid tumors.
Negative physical or emotional health outcomes resulting from high job demands with low job decision latitude.
An anxiety disorder in which the symptoms of anxiety have been determined to be etiologically related to the direct physiological effects of a substance (i.e., a drug of abuse, a medication, or toxin exposure).
A rare tumor that arises from the pineal region and affects adults. It is characterized by the presence of neuroepithelial cells and a papillary architecture. Electron microscopic studies suggest ependymal differentiation. The clinical course is variable.
A medulloblastoma characterized by marked nuclear pleomorphism, and high mitotic activity.
A disorder characterized by the acute and sudden development of changes in attention, memory, language and/or perception that can be etiologically linked to the direct physiological consequences of substance intoxication.
A disorder characterized by the acute and sudden development of changes in attention, memory, language and/or perception that can be etiologically linked to the direct physiological consequences of substance withdrawal.
A disorder involving memory impairment (either anterograde or retrograde) that is etiologically linked to the persisting effects of substance use. The memory impairment persists beyond the usual duration of substance intoxication or withdrawal.
A malignant peripheral nerve sheath tumor characterized by the presence of mesenchymal differentiation. Representative example is the malignant Triton tumor which contains a rhabdomyosarcomatous component.
A solitary fibrous tumor/hemangiopericytoma that arises from the meninges. It most often corresponds to the tumor previously diagnosed as anaplastic hemangiopericytoma.
A reference to someone other than the subject as being the one who has had an episode of the condition of interest, such as a disease.
Symptom, signs, test results in a pregnant mother childbirth.
The various distinct periods of the labor and childbirth process. It involves uterine contractions and cervical dilation to expel the fetus and for the baby to be born.
An abnormality in the position of the fetus during the labor and delivery process.
A fetal position during delivery in which the head of the fetus faces the mother's back.
An assessment of the fetus or the newborn infant for growth and size that is considered within normal ranges.
A type of labor where the labor pain or discomfort is felt by the pregnant mother in her back.
The protrusion in the perineal area during the second stage of labor. It is the characteristic sign of impending birth and is caused by increased pressure in the region.
A variation in the dimensions of the uterus.
A characteristic sign of impending birth where the anal opening becomes wider due to increased pressure in the perineal region during the second stage of labor.
A characteristic complaint in a fertile woman that is indicative of a pregnancy.
A group of disorders caused by a prenatal exposure to maternal consumption of alcohol leading to a range of behavioral, cognitive and neurological deficits in the offspring. It is characterized by physical growth problems, distinct facies, and varying psycho-neurological issues.
The site of fetal cardiac sounds that can be distinctly detected in relation to the maternal abdomen.
A stage during labor and childbirth that starts with the delivery of the placenta and lasts about two hours after delivering the baby.
The period of time prior to the beginning of childbirth labor; common signs and symptoms include nesting, anxiety, excitement, loss of mucous plug, increased urinary frequency and loose bowel movements.
A powerful, temporary tensing of the uterine muscles that is stronger than previously felt movements.
Fetal heart rate decelerations that occur with less than 50 percent of uterine contractions within a 20 minute timeframe.
An abnormal bleeding through the vagina that occurs during the last trimester of pregnancy.
A fetal position during delivery in which the head of the fetus is in the birth canal facing the area between the right hip and the spine of the mother.
The elevation of body temperature in a pregnant mother above 38 degrees C or more than 101 degrees F, and may be indicative of an infection.
A symptomatic decrease in baseline systolic or diastolic blood pressure in a pregnant woman that requires intervention.
A position of the fetus during the labor and delivery process where the fetal chin is mildly flexed but with a forward facing head.
A discharge of the mucus plug from the cervical os during cervical dilation in preparation for the labor and delivery of the baby.
A decrease in the fetal heart beat rate below 110 per minute or below the normal baseline value expected for the particular fetal age for a period of more than 10 minutes.
A physical feeling of being able to breathe better during late trimester of pregnancy when the baby starts to descend lower into the pelvic cavity.
The expulsion of the placenta with presentation of the maternal rough side first, rather than the usual fetal side of the placenta.
The separation of the placenta from the uterine wall during labor; it begins at the placental center and leads to an expulsion of the placenta after delivery of the baby.
A process in childbirth in which the placenta separates from its uterine lining, after the delivery of the baby.
The tenderness of the breasts during pregnancy due to changes in the hormonal levels and increased breast tissue growth.
Alterations in the skin's appearance during pregnancy due to hormonal level changes.
Fetal heart rate decelerations that occur with greater than or equal to 50 percent of uterine contractions within a 20 minute timeframe. Applies to early, late or variable decelerations.
A fetal position during delivery in which the fetus is in the birth canal and the back of the head is oriented towards the maternal right thigh region.
A non-sustained irregular fetal heart rate in comparison to normal baseline values.
The indicating characteristics in a pregnant mother who is in the process of labor and delivery of a fetus; common signs and symptoms include nesting, anxiety, excitement, loss of mucous plug, increased urinary frequency and loose bowel movements.
A fetal position during delivery in which the frontal part of the skull including forehead and the top of the head is first to descend into the birth canal.
A fetal position during delivery in which the face is towards one of the mother's thighs while descending into the birth canal.
A characteristic sign of impending birth in the mother during the second stage of labor; she feels like bearing down due to the pressure of the baby in the birth canal.
Atrophy or reduction of the size of the uterine corpus.
Greater than 5 contractions in 10 minutes averaged over a 30 minute window.
A reference point for the fetal position when the fetal heart rate is detected above the mother's umbilicus.
A reference point for the fetal position when the fetal heart rate is detected below the mother's umbilicus.
The fluctuations in the mental and emotional state of an individual during pregnancy.
The various distinct periods during the first stage of labor and childbirth; such as a latent, active or a transition phase.
From the onset of labor to the onset of the active phase. (reVITALize)
The period during the first stage of labor and childbirth that involves strong uterine contractions and maximal cervical dilatation.
Accelerated cervical dilation typically beginning at 6 cm.
A neoplasm that originates from histiocytes and accessory cells and affects the central nervous system. It is usually associated with the presence of identical tumors outside the central nervous system. Representative examples include Langerhans cell histiocytosis, histiocytic sarcoma, and follicular dendritic cell sarcoma.
A procedure in which tissue is heated to destroy abnormal cells. The heat may come from electric currents, microwaves, radio waves, or ultrasound. Electrodiathermy is a type of hyperthermia therapy.
A block in blood flow to the liver. It can happen while giving chemotherapy through a catheter in the hepatic artery. Sometimes doctors use drugs or other agents to cause hepatic arterial occlusion on purpose. This block of blood flow to the liver helps kill cancer cells growing in the liver.
A brief rise and then fall in the blood level of PSA (prostate-specific antigen) that occurs in some patients 1-3 years after receiving radiation treatment for prostate cancer. PSA bounce does not mean that the cancer has come back. It may be caused by the release of PSA from destroyed cancer cells or from normal prostate tissue exposed to the radiation treatment.
A group of agents that block the influx or efflux of positively charged ions through cell membrane.
A gene alteration that causes or predisposes an individual to a specific disease.
A gene mutation observed with high frequency in a group that is or was geographically or culturally isolated, in which one or more of the ancestors was a carrier of the mutant gene. This phenomenon is often called a founder effect.
A mutation that is documented to be associated with risk of disease.
A mutation that results in either no gene product or the absence of function at the phenotypic level.
A newly discovered, distinct gene alteration; NOT the same as new or de novo mutation.
An alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents, or a mutation that arises in the fertilized egg itself during early embryogenesis.
A sarcoma that arises in the bones or soft tissues following exposure to ionizing or non-ionizing radiation.
A rise in the blood level of PSA (prostate-specific antigen) in prostate cancer patients after treatment with surgery or radiation. PSA failure may occur in patients who do not have symptoms. It may mean that the cancer has come back.
A substance being studied in the treatment of liver cancer. It is made by attaching a radioactive substance called indium 111 to a monoclonal antibody called HuAFP31. HuAFP31 binds to tumor cells that make alpha fetoprotein (AFP), and the indium In 111 may kill the tumor cells. It is a type of radioimmunoconjugate.
A substance that acts quickly to treat moderate to severe pain. Opioids are like opiates, such as morphine and codeine, but are not made from opium. Opioids bind to opioid receptors in the central nervous system. A rapid-onset opioid is a type of alkaloid.
An immunoconjugate containing CC49, a monoclonal antibody (MAb) directed against the tumor-associated antigen (TAA) tumor-associated glycoprotein 72 (TAG-72), conjugated to streptavidin, a nonglycosylated homotetrameric protein that has four high affinity binding sites for biotin, with potential use in pre-targeted radioimmunotherapy (PRIT). Upon administration of anti-TAG-72 MAb CC49-streptavidin conjugate, the MAb moiety targets and binds to TAG-72 expressed on cancer cells. Upon subsequent administration of a biotin-based radioconjugate, such as yttrium Y 90 DOTA-biotin, the biotin moiety of the radioconjugate binds to the streptavidin moiety of MAb CC49-streptavidin conjugate, which localizes the biotin-conjugated radionuclide to the tumor site. Upon cellular internalization, a cytotoxic does of radiation may be specifically delivered to TAG-72-expressing tumor cells. TAG-72, a human pancarcinoma antigen, is overexpressed on a variety of cancer cell types.
A neoplastic syndrome most often caused by mutations in the hSNF5/INI1 tumor suppressor gene. It is characterized by the development of an atypical teratoid/rhabdoid tumor in infancy and early childhood. This highly aggressive tumor develops in the central nervous system as an isolated lesion or in combination with extrarenal or renal rhabdoid tumor. Patients may also develop other central nervous system malignancies including medulloblastoma, supratentorial primitive neuroectodermal tumor, and choroid plexus carcinoma.
A term used in mammography that refers to the replacement of breast tissue with fatty tissue. This commonly occurs as a woman ages.
A type of metastasis in which skin cancer spreads through a lymph vessel and begins to grow more than 2 centimeters away from the primary tumor but before it reaches the nearest lymph node.
An assessment result of the final state in a person who experienced an adverse event, which takes place after the adverse event occurs.
A reusable, ""template"" description of a possible outcome of an observation.
A reusable, ""template"" description of an allowable response to a stratification criterion.
A result of a clinical observation, i.e. from an examination, test or direct observation performed on the subject.
The finding obtained by observing, monitoring, measuring or otherwise qualitatively or quantitatively recording one or more aspects of physiologic or psychologic processes.
Information captured while conducting research on a product.
The possible or expected results that can be obtained by observing, monitoring, measuring or otherwise qualitatively or quantitatively recording one or more aspects of physiologic or psychologic processes.
The completed activity for determining issues associated with products. May be based on FDA CDRH Conclusion Codes.
Specifies whether the entity is a starting point to which other things may be compared.
Specifies whether an entity is considered a biomarker.
Specifies whether a finding or condition is clinically significant based on judgment.
Specifies whether the life of an entity has ceased.
The result or product of multiplying dimensions.
Specifies whether the entity, event or activity is considered probable or likely.
Specifies whether the subject has abstained from food and possibly water for the prescribed amount of time.
Specifies whether a planned or preestablished event or activity did not occur.
Specifies whether the position is filled.
Specifies whether this is a reappearance of an entity, event or activity.
Specifies whether the anatomical parts of the body involved in reproduction are present or absent.
Data or information that is determined by an act of observation.
The result or product of multiplying dimensions (2 or 3) of a site or specimen.
A replication incompetent adenoviral vector type 5 (Ad5) encoding the tumor suppressor gene dickkopf-3 (DKK3; Reduced Expression in Immortalized Cells; REIC; Dickkopf WNT signaling pathway inhibitor 3), and containing the super gene expression (SGE) system, composed of the triple tandem enhancer sequences of human telomerase reverse transcriptase (hTERT), simian virus 40 (SV40) and cytomegalovirus (CMV), with potential antineoplastic activity. Upon intratumoral injection and transfection of Ad5-SGE-REIC/Dkk-3, tumor cells express REIC/DKK3 protein. This may result in the activation of c-Jun-NH2-kinase (JNK) and ultimately lead to apoptosis via Bcl2 suppression and caspase-3 activation. REIC/DKK3 is expressed by healthy cells, but expression is reduced or absent in many cancer cells due to REIC/DKK3 gene defects, and this prevents tumor cell apoptosis. Increased expression of REIC/DKK3 in cancer cells may lead to an induction of tumor cell apoptosis and a reduction in tumor cell growth, while sparing normal, healthy cells expressing endogenous REIC/DKK3. The SGE system, also called C-TSC (CMV promoter driving the triple tandem enhancer sequences of hTERT, SV40 and CMV), enhances gene expression compared to more conventional adenoviral vectors.
A monoclonal antibody directed against human CD20 with potential antineoplastic activity. Anti-CD20 monoclonal antibody TL011 specifically binds to the B cell-specific cell surface antigen CD20 antigen (MS4A1; membrane-spanning 4-domains, subfamily A, member 1), thereby potentially triggering an immune response against CD20-positive B cells, leading to B cell apoptosis. CD20 is a non-glycosylated cell surface phosphoprotein that is exclusively expressed on B cells during most stages of B cell development and is often overexpressed in B-cell malignancies.
A fusion protein containing a modified form of human T-cell receptor (TCR) specific for the gp100 antigen and fused to an anti-CD3 single-chain antibody fragment, with potential antineoplastic activity. Upon direct intratumoral administration of IMCgp100 into the melanoma lesion, the TCR moiety of this agent targets and binds to the tumor associated antigen (TAA) gp100 presented on the melanoma tumor cell; the anti-CD3 fragment moiety binds to CD3- expressing T lymphocytes, thereby selectively cross-linking tumor cells and T-lymphocytes. This may lead to the recruitment of cytotoxic T lymphocytes (CTL) to the T lymphocyte/tumor cell aggregates and result in CTL-mediated death of gp100-expressing melanoma cancer cells.
A population of allogeneic, cytotoxic natural killer (NK) cells with potential antitumor activity. Allogeneic natural killer cell line MG4101 is derived from cells of a normal, healthy donor upon leukapheresis and activation.
An immunocytokine consisting of human pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha) fused to a human single-chain variable fragment (scFv) directed against the extra-domain B (ED-B) of fibronectin (L19), with potential immunopotentiating and antineoplastic activities. The L19 moiety of recombinant human fusion protein L19TNFalpha binds to the ED-B domain of fibronectin on tumor cells in the tumor neovasculature. In turn, the TNFalpha moiety may locally induce an immune response against ED-B fibronectin-expressing tumor cells and may specifically decrease the proliferation of ED-B-expressing tumor cells. ED-B is predominantly expressed during angiogenesis and tumor growth.
A cancer vaccine comprised of 11 peptides associated with glioblastoma multiforme (GBM), with potential immunomodulating and antineoplastic activities. Vaccination with glioblastoma multiforme multi-antigen vaccine IMA950 stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response as well as a T-helper (Th) immune response against tumor cells expressing these peptides, potentially resulting in decreased tumor growth of GBM. Peptides in IMA950 consist of the following: brevican (BCAN); chondroitin sulfate proteoglycan 4 (CSPG4); fatty acid binding protein 7, brain (FABP7); insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3); neuroligin 4, X-linked (NLGN4X); neuronal cell adhesion molecule (NRCAM); protein tyrosine phosphatase, receptor-type, Z polypeptide 1 (PTPRZ1); tenascin C (TNC); Met proto-oncogene (MET); baculoviral IAP repeat-containing 5 (BIRC5); and hepatitis B virus core antigen.
A small-molecule inhibitor of choline kinase alpha (CHKA), with potential antineoplastic activity. TCD-717 targets and binds to CHKA, an enzyme that plays a key role in the synthesis of phosphatidylcholine, the major phospholipid in eukaryotic cell membranes. Blockade of this enzyme induces cells to activate a different route for phospholipid production which causes a toxic effect and eventually leads to cell destruction. CHKA, overexpressed in human cancer cells while only minimally expressed in normal cells, appears to play a significant role in cellular proliferation, evasion of apoptosis, increased cell motility and metastasis.
A peptide vaccine against the immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO), with potential immunomodulating and antineoplastic activities. Vaccination with indoleamine 2,3-dioxygenase peptide vaccine may activate the immune system to induce an immune response against IDO-expressing cells. This may increase and restore the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes, and may eradicate IDO-expressing tumor cells. IDO, a cytosolic enzyme responsible for tryptophan catabolism and conversion of tryptophan into kynurenine, is overexpressed by a variety of tumor cell types and antigen presenting cells (APCs) and plays an important role in immunosuppression; Tryptophan depletion inhibits T-lymphocyte proliferation and activation, and suppresses the immune system.
An autologous dendritic cell (DC) cancer vaccine with potential immunostimulatory activity. GITRL RNA-transfected autologous DC vaccine is prepared by transfecting DCs with RNAs encoding tumor necrosis factor (ligand) superfamily, member 18 (TNFSF18 or GlTRL); expression of GlTRL results in modulating T lymphocyte survival in peripheral tissues. Co-vaccination of this vaccine with melanoma antigen specific vaccine may eliminate the adverse effects associated with systemic administration of immune modulators, while also enhancing vaccine-induced immune responses.
An autologous dendritic cell (DC) cancer vaccine with potential immunostimulatory activity. Anti-CTLA4 MoAb RNA-transfected autologous DC vaccine is prepared by transfecting DCs with RNAs encoding humanized heavy and light chains of the anti-CTLA4 (cytotoxic T-Lymphocyte-Associated Antigen 4); expression of anti-CTLA4 blocks the inhibitory effect of CTLA4 on the activation of T-lymphocytes. Co-vaccination of this vaccine with melanoma antigen specific vaccine may eliminate the adverse effects associated with systemic administration of immune modulators, while also enhancing vaccine-induced immune responses.
An autologous dendritic cell (DC) cancer vaccine with potential immunostimulatory activity. Anti-CTLA4 MoAb RNA/GITRL RNA-transfected DC vaccine is prepared by transfecting DCs with RNAs encoding humanized heavy and light chains of the anti-CTLA4 (cytotoxic T-Lymphocyte-Associated Antigen 4) monoclonal antibody and tumor necrosis factor (ligand) superfamily, member 18 (TNFSF18 or GlTRL); expression of anti-CTLA4 blocks the inhibitory effect of CTLA4 on the activation of T-lymphocytes, while expression of GlTRL modulates T lymphocyte survival in peripheral tissues. Co-vaccination of this vaccine with melanoma antigen specific vaccine may eliminate the adverse effects associated with systemic administration of immune modulators, while also enhancing vaccine-induced immune responses.
A tetravalent bispecific antibody directed against human CD30 and the human low affinity IgG Fc region receptor (FCGR3A; CD16A), with potential immunomodulating and antineoplastic activities. Anti-CD30/CD16A monoclonal antibody AFM13 binds to the CD16A expressed on natural killer (NK) cells with two of its binding sites and to CD30 on CD30-expressing tumor cells with the other two binding sites, thereby selectively cross-linking tumor and NK cells. This may result in NK cell activation, antibody-dependent cellular cytotoxicity (ADCC) and eventually tumor cell lysis. CD30, a cell surface receptor and a member of the tumor necrosis factor (TNF) receptor superfamily, is overexpressed in hematologic malignancies; CD16A is specifically expressed on the surface of NK cells.
A humanized monoclonal antibody recognizing the tumor-specific epitope of mucin-1 (TA-MUC1), with potential antineoplastic activity. Anti-TA-MUC1 monoclonal antibody PankoMab targets and binds to the TA-MUC1 epitopes expressed on the cell surface of tumor cells, thereby potentially activating the immune system to induce an antibody-dependent cellular cytotoxicity (ADCC) against the TA-MUC1-expressing tumor cells. TA-MUC1 is designated to MUC1 epitopes with O-glycosylated carbohydrate-induced conformational structures that are tumor-specific, thereby enabling PankoMab to differentiate between tumor MUC1 and non-tumor MUC1 epitopes.
A glycoengineered form of a human monoclonal antibody directed against the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Anti-EGFR monoclonal antibody GT-MAB 5.2-GEX specifically binds to the extracellular domain of EGFR, thereby potentially inducing an antibody-dependent cell-mediated cytotoxicity (ADCC) against EGFR-expressing tumor cells, eventually leading to tumor cell apoptosis and an inhibition of tumor cell growth. EGFR, a member of the epidermal growth factor family of extracellular protein ligands, is overexpressed on the cell surfaces of various solid tumors. This antibody has a specific glycosylation profile that may enhance its ADCC response against EGFR-expressing tumor cells.
A cancer vaccine containing the HLA-A*2402-restricted peptide epitope derived from cell division associated gene 1 (CDCA1), with potential immunostimulatory and antitumor activities. Upon administration, HLA-A*2402-restricted CDCA1-A24-56 peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against CDCA1-expressing tumor cells, resulting in tumor cell lysis and decreased tumor cell proliferation. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
An orally bioavailable, highly soluble phosphate prodrug of B-raf (BRAF) protein kinase with potential antineoplastic activity. BRAF inhibitor ARQ 736 is converted into its active form ARQ 680 in the presence of phosphatases. In turn, ARQ 680 selectively binds to and inhibits the activity of oncogenic B-raf, which may inhibit the proliferation of tumor cells expressing mutated B-raf gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. The valine to glutamic acid substitution at residue 600 (V600E) accounts for about 90% of BRAF gene mutations.
A histone deacetylase (HDAC) inhibitor with potential antineoplastic activity. CG200745 inhibits the catalytic activity of HDAC, resulting in an accumulation of highly acetylated chromatin histones, followed by the induction of chromatin remodeling and an altered pattern of gene expression. In particular, this agent enhances the histone acetylation of the tumor suppressor gene p53. This results in an accumulation of p53, p53-dependent transactivation and apoptosis in tumor cells. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins.
A substance being studied in the imaging of some types of cancer. M5A is a monoclonal antibody that binds to a protein called CEA on the surface of some tumor cells. It is linked to a radioisotope called indium In 111. The combined substance is injected into the blood, and a machine is used to find cells in the body that bind to it. Indium In 111 anti-CEA monoclonal antibody M5A is a type of radioimmunoconjugate.
Describes cells that have a protein that binds to androgens (male hormones). Cancer cells that are AR+ may need androgens to grow. These cells may stop growing or die when they are treated with substances that block the binding and actions of androgen hormones.
In mycosis fungoides, an area of skin that is thickened, raised, red, scaly, and itchy.
In traditional Chinese medicine, a condition described as slowing or pooling of blood, which may cause pain or other symptoms.
Necrosis of the mandible or maxilla in patients receiving intravenous or oral bisphosphonate therapy. It usually manifests with slow healing or failure to heal of a jaw bone following oral surgery. In a minority of cases, the necrosis appears spontaneously. Signs and symptoms include pain, swelling and infection of the affected area.
A solid, low grade, spindle cell, glial neoplasm of adults that originates in the neurohypophysis or infundibulum. Clinical signs and symptoms include visual disturbance, headache and features of hypopituitarism. Pituicytomas are well-circumscribed, solid masses that can measure up to several centimeters. Histologically, they show a compact architecture consisting of elongate, bipolar spindle cells arranged in interlacing fascicles or assuming a storiform pattern.
A finding indicating that two or more tumors have merged to create a single cancerous mass.
A finding indicating that a tumor mass has been divided into two or more tumors.
A qualitative or quantitative measurement of the response of a target tumor(s) to the therapy.
A qualitative or quantitative measurement of the response of a non-target tumor(s) to the therapy.
The most clinically favorable response recorded from the start of the study treatment until the end of treatment.
A very rare, WHO grade I, non-endocrine neoplasm that arises in the anterior lobe of the pituitary gland and described in adults. Its histogenesis is uncertain, although it has been suggested that it is derived from the folliculo-stellate cells of the adenohypophysis. It is characterized by the presence of spindle cells with eosinophilic, granular cytoplasm forming fascicles. Electron microscopic studies demonstrate the accumulation of intracytoplasmic mitochondria and lack of secretory granules. Immunohistochemical studies are negative for pituitary hormones. Patients may present with pituitary hypofunction, visual disturbances, headache, nausea and vomiting. The clinical course is usually benign.
A lump of tissue with spikes or points on the surface.
A functioning or non-functioning endocrine neoplasm that arises from the anterior lobe of the pituitary gland. It is classified either as adenoma or carcinoma.
Tooth decay that extends through the enamel into the dentin layer.
Tooth decay that is restricted to the enamel layer.
Noise in the temporomandibular joint, with or without pain, when fully opening the jaw.
Projection of a tooth beyond its normal position.
Tingling, numbness, heaviness, and other feelings that occur after an acupuncture needle has been properly placed in the body. The needle may be twirled, moved up and down at different speeds and depths, heated, or charged with a small electric current until the de qi sensation occurs.
Too much or too little of any substance that helps the body work the way it should. A chemical imbalance may be caused by certain tumors and can cause changes in behavior or emotion.
A morphologic finding indicating the presence of necrotic epithelial cells, neutrophils, karyorrhectic debris, and fibrin in the lumen of malignant glands. It was initially described in colonic adenocarcinomas, but it has also been observed in adenocarcinomas that arise in other anatomic sites, including lungs and ovaries.
A neoplastic process in the cervix characterized by morphologic features of both moderate and severe intraepithelial neoplasia.
A hormone producing endocrine neoplasm, associated with a hormonal syndrome.
A hormone producing or non-producing endocrine neoplasm, not associated with a hormonal syndrome.
A neuroglial tumor that arises from the middle portion of the brain stem. It usually affects children and has a poor prognosis.
A breast carcinoma characterized by the presence of multiple cancerous tumors that originate from the same clone and are usually located in the same quadrant of the breast.
A term that usually refers to cancer growth and is defined by the presence of multiple lesions, each originating from a different clonal cellular population.
A breast carcinoma characterized by the presence of multiple cancerous tumors that originate from different clones and are usually located in different quadrants of the breast.
Breast carcinoma that has not spread beyond the breast and the axillary lymph nodes.
For hepatocellular carcinoma: Stage I includes: T1, N0, M0. T1: Solitary tumor without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. For intrahepatic cholangiocarcinoma: Stage I includes: T1, N0, M0. T1: Solitary tumor without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
For hepatocellular carcinoma: Stage II includes: T2, N0, M0. T2: Solitary tumor with vascular invasion or multiple tumors none more than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. For intrahepatic cholangiocarcinoma: Stage II includes: T2, N0, M0. T2: Solitary tumor with vascular invasion or multiple tumors, with or without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
For hepatocellular carcinoma: Stage IIIA includes: T3a, N0, M0. T3a: Multiple tumors more than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
For hepatocellular carcinoma: Stage IIIB includes: T3b, N0, M0. T3b: Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
For hepatocellular carcinoma: Stage IV includes: IVA: (Any T, N1, M0); IVB: (Any T, Any N, M1). N1: Regional lymph node metastasis. M0: No distant metastasis. M1: Distant metastasis. For intrahepatic cholangiocarcinoma: Stage IVA includes: (T4, N0, M0); (Any T, N1, M0). T4: Tumor with periductal invasion. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 7th Ed.)
The reemergence of a malignant neoplasm after a period of remission at the site of the original tumor or adjacent to it.
A group of inherited genetic hematopoietic stem cell disorders characterized by bone marrow failure that involves one or more cell lines. Representative examples include Fanconi anemia, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome.
A morphologic finding indicating that the cutaneous melanoma is confined to the epidermis and does not invade the dermis.
A morphologic finding indicating that the cutaneous melanoma has invaded part of the papillary dermis but the malignant cellular infiltrate has not reached the papillary-reticular dermis interface.
A morphologic finding indicating that the cutaneous melanoma has invaded the entire thickness of the papillary dermis but the malignant cellular infiltrate does not extend into the reticular dermis.
A morphologic finding indicating that the cutaneous melanoma has invaded the reticular dermis.
A morphologic finding indicating that the cutaneous melanoma has invaded the subcutaneous tissue.
A group of syndromes caused by genetic birth defects that may lead to the development of malignancies. It is characterized by a large body size or large body parts at birth, or excessive body growth early in childhood. Representative examples include neurofibromatosis, Beckwith-Wiedemann syndrome, and Sturge-Weber syndrome.
Leukoplakia of the oral mucosa that is clinically characterized by the presence of erythematous or red and white patches.
An autoimmune acute encephalitis caused by antibodies against the glutamate NMDA receptor. It usually affects females and in the majority of cases it is associated with the presence of a tumor, most commonly an ovarian teratoma. The presence of a tumor in patients with this form of encephalitis implies that the latter is a paraneoplastic syndrome. It is manifested with psychiatric symptoms and epileptic seizures. It is a potentially lethal disorder; however, it is usually reversible with the prompt removal of the tumor.
A finding regarding a female's pregnancy and lactation situation.
A humanized, Fc disabled anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) monoclonal antibody (MoAb) with immunomodulating activity. Anti-human GITR MoAb TRX518 blocks the interaction of GITR, found on multiple types of T cells, with its ligand, thereby inducing both the activation of tumor-antigen-specific T effector cells, as well as abrogating the suppression induced by inappropriately activated T regulatory cells. This agent is shown to act synergistically with chemotherapeutic drugs in multiple cancer models.
An anti-idiotype murine monoclonal antibody (MoAb) specific to P3 MoAb with anti-metastatic effect. Racotumomab binds to the idiotype region of P3 MoAb and functionally mimics the three-dimensional structure of N-glycolyl ceramides of mono-sialyl lactose, the antigenic target of P3. As a result, this anti-idiotype antibody may stimulate the host immune system to elicit humoral and cellular immune responses against tumor cells expressing NeuGc-GM3 gangliosides, which are expressed in a wide variety of tumor cells.
A fully human monoclonal antibody (MoAb) against human A1 domain of tenascin-C, in small immunoprotein (SIP) format conjugated with iodine 131 with potential antineoplastic activity. Iodine I 131 MoAb F16SIP binds to tenascin-C on the vascular tissues and delivers cytotoxic radiation to the tumors, thereby minimizing systemic radiotoxicity. Tenascin-C is a glycoprotein of the extracellular matrix, and the large isoform of this matrix protein is expressed and restricted around vascular structures in the tumor stroma of a variety of different tumors.
A long-acting, pegylated variant of filgrastim (recombinant human granulocyte colony-stimulating factor (G-CSF)) with immunomodulating activity. Similar to endogenous G-CSF, this agent binds to and activates specific cell surface receptors, stimulating neutrophil progenitor proliferation and differentiation and selected neutrophil functions. The modification of this version of filgrastim with the addition of a Y-shaped branch of polyethylene glycol at a specific lysine residue (Lys 17) theoretically serves to extend the half-life of the agent.
A liposarcoma that arises from the thymus gland. It is characterized by the presence of a liposarcomatous malignant infiltrate that entraps lobules of thymic tissue.
A benign or malignant mesenchymal neoplasm that arises from the thymus gland. It is characterized by the presence of spindle cell fibroblasts and collagen tissue.
A thymoma that arises in the cervical region and is not connected with the thymus gland.
A Hodgkin lymphoma that arises from the thymus gland. It is usually of the nodular sclerosis subtype and is often associated with cystic changes in the thymic epithelium.
A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. Lenvatinib blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis.
The potassium salt form of fenquizone, a quinazolinone structurally related to metolazone, and sulphonamide-based diuretic with diuretic activity. As a thiazide-like diuretic, fenquizone acts by blocking reabsorption of sodium in the proximal tubule and the ascending branch of the loop of Henle. This causes an increase in diuresis with the elimination of chloride and sodium.
A subjective answer that something rarely happens.
A subjective answer that something occurs relatively frequently.
A chromosomal translocation that involves the chromosomes 4 and 14.
A chromosomal translocation that involves the chromosomes 14 and 16.
The potassium salt of a narrow-spectrum, semisynthetic penicillin derivative with antibacterial activity. Azidocillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This interrupts bacterial cell wall synthesis and results in the weakening of the bacterial cell wall, eventually causing cell lysis.
Stage IIA1 includes: T2a1, N0, M0. Tumor invades beyond uterus but no to pelvic wall or to lower third of vagina. No parametrial invasion. T2a1: Clinically visible lesion 4.0 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIA2 includes: T2a2, N0, M0. Tumor invades beyond uterus but no to pelvic wall or to lower third of vagina. No parametrial invasion. T2a2: Clinically visible lesion more than 4.0 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIC1 includes: T1-T3, N1, M0. T1: Tumor confined to corpus uteri. T2: Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus. T3: Tumor involves serosa and/or adnexa, vagina, or parametrial tissue. N1: Regional lymph node metastasis to pelvic lymph nodes. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
Stage IIIC2 includes: T1-T3, N2, M0. T1: Tumor confined to corpus uteri. T2: Tumor invades stromal connective tissue of the cervix but does not extend beyond uterus. T3: Tumor involves serosa and/or adnexa, vagina, or parametrial tissue. N2: Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. M0: No distant metastasis. This staging applies to carcinomas and carcinosarcomas. (AJCC 7th ed.)
A radioconjugate consisting of dextromethorphan, a synthetic, methylated dextrorotatory analogue of levorphanol, conjugated with carbon-13 [(13)C] with radiotracer activity. (13)C-dextromethorphan can be used in a breath-test phenotype assay of CYP2D6 activity, based on the principle that CYP2D6-mediated O-demethylation cleaves a (13)CH3 that enters the body's carbon pool to be eliminated ultimately as (13)CO2 in expired air, which can be measured. The (13)C-dextromethorphan breath test may prove useful in identifying poor CYP2D6 metabolizers of such important clinical drugs as tamoxifen.
A combination preparation containing sodium bicarbonate, potassium bicarbonate, and anhydrous citric acid, with acid-neutralizing properties. This combination in water principally contains the antacids potassium citrate and sodium citrate, and is used for the relief of acid indigestion and heartburn. This combination does not contain aspirin, and therefore does not exert aspirin's analgesic or anti-inflammatory effects.
An orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential antineoplastic activity. PARP inhibitor AZD2461 selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks and promotes genomic instability and eventually leads to apoptosis. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks.
A synthetic heparan sulfate mimetic with potential anti-angiogenic and antineoplastic activity. PG545 inhibits the cleavage of heparan sulfate from cell surface proteoglycan by heparanase and thus inhibits the neovascularization induced by interaction between heparan sulfate and other extracellular matrix proteins. In this manner, this agent may have the potential to slow the progression of growth of solid tumors.
An orally bioavailable inhibitor of the proto-oncogene c-Met with potential antineoplastic activity. c-Met inhibitor AMG 337 selectively binds to c-Met, thereby disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met protein, the product of the proto-oncogene c-Met, is a receptor tyrosine kinase also known as hepatocyte growth factor receptor (HGFR); this protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis.
A lipopeptide-based, vascular endothelial growth factor receptor 2 (VEGRF2) -targeted contrast agent with the property of molecular imaging of angiogenesis. BR55 is prepared by incorporation of a biospecific heterodimer peptide into the perfluorobutane-containing lipid-shelled microbubble membrane; the peptide specifically binds to VEGFR2 expressed on tumoral vascular endothelium allowing ultrasound imaging of the sites of active angiogenesis.
A cancer vaccine containing five HLA-A*2402-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from CDCA1 (cell division cycle-associated protein 1), URLC10 (up-regulated lung cancer 10), KIF20A (kinesin-like family member 20A), DEPDC1 (DEP domain containing 1), and MPHOSPH1 (M phase phosphoprotein 1). Upon administration, this peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against CDCA1-,URLC10-,KIF20A-,DEPDC1-, or MPHOSPH1-expressing tumor cells, resulting in tumor cell lysis and decreased tumor growth. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A synthetic triazene derivative with antineoplastic activity. Upon metabolic activation via N-demethylation, TriN2755 is converted into highly reactive carbocations that can alkylate DNA and other macromolecules, thereby resulting in DNA cross links, inhibiting DNA replication and repair, and subsequently inducing apoptosis. This agent has high hydrophilicity and photostability and shows a favorable toxicity profile over the other triazenes.
A cancer vaccine containing two HLA-A*2402-restricted peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from vascular endothelial growth factor receptors (VEGFRs) 1 and 2. Upon administration, this peptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against VEGFR1- and VEGFR2-expressing tumor cells, resulting in tumor cell lysis and decreased tumor growth. HLA-A*2402 is an MHC class I molecule that presents antigenic peptides to CD8+ T cells; epitope design restricted to epitopes that bind most efficiently to HLA-A*2402 may improve antigenic peptide immunogenicity.
A cancer vaccine containing multiple peptide epitopes with potential immunostimulatory and antitumor activities. Peptide epitopes in this vaccine are derived from, URLC10 (up-regulated lung cancer 10), CDCA1 (cell division cycle-associated protein 1), KOC1 (IGF II mRNA Binding Protein 3). Upon administration, URLC10-CDCA1-KOC1 multipeptide vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tumor cells expressing URLC10, CDCA1, KCO1 peptides, resulting in cell lysis and decreased tumor growth.
A whole cell vaccine comprised of irradiated allogeneic renal cell carcinoma (RCC) with potential immunostimulating and antineoplastic activities. Allogeneic renal cell carcinoma vaccine MGN1601 contains two active ingredients: 1) genetically modified allogeneic RCC cells that are transiently transfected with four different MIDGE (Minimalistic Immunogenically Defined Gene Expression) vectors encoding IL-7, GM-CSF, CD80 and CD154 and 2) the synthetic DNA-based immunomodulator dSLIM-30L1, a TLR9 agonist.. Vaccination results in expression of IL-7, GM-CSF, CD80 and CD154, which all contribute to the activation or enhancement of immune responses. Furthermore, administration of this RCC vaccine may elicit a cytotoxic T lymphocyte (CTL) response against similar host tumor cells, resulting in decreased tumor growth. TLR9 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.
A highly modified, fourth generation linear decapeptide with gonadotropin-releasing hormone (GnRH or LHRH) antagonizing properties. Ozarelix competitively binds to and blocks the gonadotropin releasing hormone receptor in the anterior pituitary gland, thereby inhibiting the secretion and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone. As a result, this may relieve symptoms associated with hormonally dependent disease states such as hormone-dependent prostate cancer.
The hydrochloride salt of nilotinib, an orally bioavailable aminopyrimidine-derivative Bcr-Abl tyrosine kinase inhibitor with antineoplastic activity. Designed to overcome imatinib resistance, nilotinib binds to and stabilizes the inactive conformation of the kinase domain of the Abl protein of the Bcr-Abl fusion protein, resulting in the inhibition of the Bcr-Abl-mediated proliferation of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) cells. This agent also inhibits the receptor tyrosine kinases platelet-derived growth factor receptor (PDGF-R) and c-kit, a receptor tyrosine kinase mutated and constitutively activated in most gastrointestinal stromal tumors (GISTs). With a binding mode that is energetically more favorable than that of imatinib, nilotinib has been shown to have an approximately 20-fold increased potency in kinase and proliferation assays compared to imatinib.
The difumarate salt of saracatinib, an orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption.
The sulfate salt of selumetinib, an orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) 1 and 2. MEK 1 and 2 are dual specificity kinases that are essential mediators in the activation of the RAS/RAF/MEK/ERK pathway, are often upregulated in various cancer cells, and are drivers of diverse cellular responses, including proliferation. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.
The tosylate salt form of varlitinib, an orally bioavailable inhibitor of the epidermal growth factor receptor family with potential antineoplastic activity. Varlitinib selectively and reversibly binds to both EGFR (ErbB-1) and Her-2/neu (ErbB-2) and prevents their phosphorylation and activation, which may result in inhibition of the associated signal transduction pathways, inhibition of cellular proliferation and cell death. EGFR and Her-2 play important roles in cell proliferation and differentiation and are upregulated in various human tumor cell types. Due to the dual inhibition of both EGFR and Her-2, this agent may be therapeutically more effective than agents that inhibit EGFR or Her-2 alone.
The anhydrous form of fostamatinib disodium, an orally available Syk kinase inhibitor with potential anti-inflammatory and immunomodulating activities. Fostamatinib inhibits Syk kinase-mediated IgG Fc gamma receptor signaling, resulting in inhibition of the activation of mast cells, macrophages, and B-cells and related inflammatory responses and tissue damage. Syk kinase, widely expressed in hematopoietic cells, is a nonreceptor tyrosine kinase that is involved in coupling activated immunoreceptors to signal downstream events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis.
The hydrochloride salt form of buformin, an agent belonging to the biguanide class of antidiabetics with antihyperglycemic activity. Buformin is not metabolized and is excreted in the urine. This agent has an elevated risk of causing lactic acidosis, and has been withdrawn from the market.
A reusable template description of a sign, symptom, disease, or other medical occurrence. EXAMPLE(S):death, back pain, headache, pulmonary embolism, heart attack, pregnancy, flu, broken bone, menstrual period, depression; OTHER NAME(S):Clinical Events, Medical History.
A reusable, template description of any unfavorable and unintended sign, symptom, disease, or other medical occurrence with a temporal association with the use of a medical product, procedure or other therapy, or in conjunction with a research study, regardless of causal relationship. EXAMPLE(S):death, back pain, headache, pulmonary embolism, heart attack.
A neoplastic lesion that shows morphologic evidence of invasion into the lamina propria or muscularis mucosa. There is no evidence of invasion into the submucosa. Evidence of invasion may refer to stromal invasion by single cells or clusters of cells, presence of atypical and complex glandular architectural patterns beyond those that are present in normal mucosa, desmoplasia, and/or vascular invasion.
A high grade poorly differentiated carcinoma arising from the digestive system. It is composed of small or large neoplastic cells that express immunohistochemical evidence of neuroendocrine differentiation. There is marked nuclear atypia, necrosis, and more than 20 mitoses per 10 HPF.
A carcinoma that arises from the digestive system and is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30% of either component should be present for the diagnosis to be made.
A pancreatic ductal adenocarcinoma characterized by the presence of duct-like structures and medium-sized malignant glandular structures.
A pancreatic ductal adenocarcinoma characterized by the presence of medium-sized duct-like structures and small malignant tubular glandular structures.
A pancreatic ductal adenocarcinoma characterized by the presence of small and irregular malignant glandular structures, solid sheets of malignant cells, and single malignant cells.
A pancreatic intraepithelial neoplasia characterized by the presence of tall columnar cells that form flat architectural patterns. Mild cytological atypia is present.
A pancreatic intraepithelial neoplasia characterized by the presence of tall columnar cells that form papillary, micropapillary, or basally pseudostratified architectural patterns. Mild cytological atypia is present.
A pancreatic lesion microscopically resembling pancreatic intraepithelial neoplasia-1A, however the neoplastic nature of the pathologic process has not been unambiguously established.
A pancreatic epithelial neoplasia characterized by the presence of papillary and rarely flat architectural patterns with formation of cribriform patterns and luminal necrosis. Severe cytological atypia is present.
A carcinoma that arises from the pancreas showing either extensive mucin accumulation and acinar neoplastic cells or a mixture of columnar or signet-ring cells and acinar neoplastic cells.
A very rare carcinoma that arises from the pancreas showing a mixture of acinar, neuroendocrine, and ductal carcinoma elements.
A rare adenocarcinoma that arises from the pancreas. It is characterized by marked hepatocellular differentiation.
A pancreatic ductal adenocarcinoma characterized by poor differentiation and a prominent syncytial growth pattern. The prognosis is more favorable compared to conventional pancreatic ductal adenocarcinoma.
A benign, non-metastasizing, usually cystic epithelial neoplasm arising from the exocrine pancreas. It is composed of glycogen-rich epithelial cells which produce a watery fluid. Signs and symptoms include abdominal mass, abdominal pain, nausea, vomiting, and weight loss.
A benign, non-metastasizing epithelial neoplasm arising from the exocrine pancreas. It is characterized by the presence of a few large cysts and is composed of glycogen-rich epithelial cells which produce a watery fluid.
A well-circumscribed serous adenoma that is solid and lacks cystic changes.
A serous adenoma that develops in a patient with Von Hippel-Lindau syndrome. Usually there are multiple serous adenomas present of the macrocystic type.
A non-invasive mucinous cystic neoplasm that arises from the pancreas and is characterized by the presence of mild dysplasia and absence of mitotic figures.
A cystic epithelial neoplasm characterized by the presence of columnar mucin-producing epithelial cells, ovarian-type stroma formation, and the absence of an invasive carcinomatous component.
A non-invasive mucinous cystic neoplasm that arises from the pancreas and is characterized by the presence of severe dysplasia. The neoplastic columnar mucin-producing epithelial cells form papillae with irregular branching and budding. There is nuclear stratification, prominent nucleoli, and cellular pleomorphism. Mitotic activity is present and the mitoses may be atypical.
A group of cystic or mass-forming epithelial neoplasms that arise from the exocrine pancreas, exhibit ductal differentiation, and grow mostly within the pancreatic ducts. This group includes the pancreatic intraductal papillary mucinous neoplasms and the pancreatic intraductal tubulopapillary neoplasms.
An epithelial neoplasm that arises from the exocrine pancreas characterized by the formation of tubular structures, high grade dysplasia, and ductal differentiation. Grossly, it is characterized by the presence of intraductal nodular masses. Morphologically, there are nodules of tubular glands and occasional papillary structures growing in dilated ducts. There is no significant mucin production. Signs and symptoms include epigastric pain, weight loss, vomiting, steatorrhea, and diabetes mellitus.
A pancreatic intraductal tubulopapillary neoplasm characterized by the presence of an invasive carcinomatous component. The invasive carcinoma has a tubular pattern.
A pancreatic intraductal papillary mucinous neoplasm characterized by the presence of neoplastic epithelial cells that are similar to gastric foveolar epithelial cells.
A morphologic finding indicating the presence of cells that resemble gastric foveolar epithelial cells.
A pancreatic intraductal papillary mucinous neoplasm characterized by the presence of neoplastic epithelial cells that form tall papillae, similar to those that are present in colonic villous adenomas.
A morphologic architectural pattern indicating the presence of tall papillary structures.
A pancreatic intraductal papillary mucinous neoplasm characterized by the presence of neoplastic epithelial cells that form thin-branching papillae and exhibit high grade dysplasia.
A morphologic architectural pattern indicating the presence of papillary structures forming thin branches.
A pancreatic intraductal papillary mucinous neoplasm characterized by the presence of neoplastic epithelial cells with abundant eosinophilic granular cytoplasm.
A condition in which a person is heterozygous for a globin gene, with a one normal allele and one defective allele.
A state in which both beta-globin alleles code for a C or E variant but which leads to such minor changes to the hemoglobin that it does not cause disease.
A heterozygous state in which a person has a mutation in a beta globin allele causing beta thalassemia, together with other structural variants in the other allele.
An epithelial neoplasm that arises from the exocrine pancreas. It is characterized by the presence of neoplastic cells that resemble acinar cells and produce pancreatic exocrine enzymes. The vast majority are carcinomas.
A benign, cystic acinar cell neoplasm that arises from the exocrine pancreas. The cysts are lined by well-differentiated cells which show acinar differentiation.
A mature or immature teratoma that arises from the pancreas.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the pancreas. It is characterized by the presence of malignant large cells.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the pancreas. It is characterized by the presence of malignant small cells.
A low grade well differentiated tumor with neuroendocrine differentiation that arises from the pancreas. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal or less than 2%.
A low grade well differentiated tumor with neuroendocrine differentiation that arises from the pancreas. It is characterized by the absence of a hormone-related clinical syndrome.
An esophageal squamous cell carcinoma characterized by the presence of a spindle-cell carcinomatous component. Crossly it has a polypoid appearance and usually arises from the middle or lower third of the esophagus.
A reactive (non-neoplastic) hyperplastic process affecting the esophageal squamous epithelium that is caused by inflammation. Morphologically it involves more than 15% of the thickness of the esophageal squamous epithelium. Its association with an increase risk of developing squamous cell carcinoma remains controversial.
An esophageal squamous cell carcinoma characterized by the presence of prominent keratinization and low mitotic activity.
An esophageal squamous cell carcinoma characterized by the presence of variable morphologic characteristics that include areas of prominent and poor keratinization.
An esophageal squamous cell carcinoma characterized by the presence of basal-like malignant squamous cells that form nests, often associated with central necrosis.
Glandular intraepithelial neoplasia arising in Barrett esophagus.
A finding indicating the presence of Barrett esophagus with regenerative changes only.
A finding indicating the presence of Barrett esophagus in which technical reasons make the interpretation of atypia difficult, atypia is present but it is not quite to the level of dysplasia, or atypia is present at the bases of the crypts but does not reach the surface of the crypts.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the esophagus.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the esophagus. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the esophagus. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the esophagus. It is characterized by the presence of malignant large cells.
A carcinoma that arises from the esophagus and is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
A capillary or cavernous hemangioma that arises from the esophagus. The majority of cases are polypoid intraluminal lesions.
A rhabdomyosarcoma arising from the esophageal wall.
A synovial sarcoma that affects the esophageal wall.
An extranodal diffuse large B-cell lymphoma that arises from the esophagus with the bulk of the mass located in the esophagus.
An extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue that arises from the esophagus with the bulk of the mass located in the esophagus.
A radioimmunoconjugate containing the murine IgG1 anti-CD45 monoclonal antibody (MoAb) BC8 labeled with yttrium 90 (Y90), with potential immunotherapeutic activity. Yttrium Y 90 anti-CD45 monoclonal antibody BC8 binds to CD45 antigen, a receptor protein-tyrosine phosphatase expressed on the surface of both normal and malignant hematopoietic cells. After binding and internalization by CD45-expressing tumor cells, this agent may deliver a cytotoxic dose of beta radiation.
The tosylate salt form of ANA773, a Toll-Like Receptor 7 (TLR7) agonist prodrug with potential immunostimulating activity. Upon oral administration, ANA773 is metabolized into its active form that binds to and activates TLR7, thereby stimulating dendritic cells (DCs) and enhancing natural killer cell (NK) cytotoxicity. This activation results in the production of proinflammatory cytokines, including interferon alpha, and enhanced antibody-dependent cellular cytotoxicity (ADCC). TLR7 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.
A small molecule with potential anticachexia activity. The anticachexia agent MT-102 may increase protein synthesis and decrease muscle protein breakdown. This may result in improved body weight, muscle mass and may improve weakness and fatigue associated with cancer-related cachexia.
An orally available small molecule targeting a subset of Janus-associated kinase (JAK) with potential antineoplastic activity. JAK2 inhibitor BMS-911543 selectively inhibits JAK2, thereby preventing the JAK/STAT (signal transducer and activator of transcription) signaling cascade, including activation of STAT3. This may lead to an induction of tumor cell apoptosis and a decrease in cellular proliferation. JAK2, often upregulated or mutated in a variety of cancer cells, mediates STAT3 activation and plays a key role in tumor cell proliferation and survival.
A synthetic mustard compound of the tromethamine (tris) salt of palifosfamide (Isophosphamide mustard), with potential antineoplastic activity. As the stabilized active metabolite of ifosfamide, palifosfamide irreversibly alkylates and crosslinks DNA through GC base pairs, resulting in irreparable 7-atom interstrand crosslinks. This leads to an inhibition of DNA replication and ultimately cell death. Unlike ifosfamide, this agent is not metabolized to acrolein or chloroacetaldehyde, metabolites associated with bladder and CNS toxicities. In addition, because palifosfamide does not require activation by aldehyde dehydrogenase, it may overcome the tumor resistance seen with ifosfamide. Stabilization with tris instead of lysine further increases stability and may further decrease nephrotoxicity.
A fully human IgG1 monoclonal antibody against angiopoietin 2 (ANG2), with potential antiangiogenic activity. Anti-ANG2 monoclonal antibody MEDI-3617 binds to Ang2 and interferes with the interaction between Ang2 and its receptor TEK tyrosine kinase (Tie2), thereby resulting in the disruption of vascular remodeling. This may inhibit angiogenesis and may eventually lead to an inhibition of tumor cell proliferation.
A peptide vaccine containing a 15-mer peptide (DLAQMFFCFKELEGW), with C to M alteration at amino acid position 57, derived from the anti-apoptosis protein survivin, and conjugated with keyhole limpet hemocyanin (KLH), with potential immunopotentiating and antineoplastic activities. Upon subcutaneous administration of SVN53-67/M57-KLH peptide vaccine, this peptide is able to bind both HMC class I and II molecules and may activate the immune system to mount a cytotoxic T-lymphocyte (CTL) as well as a T-helper cell response against survivin-expressing cancer cells. This may result in decreased tumor cell proliferation and ultimately tumor cell death. Survivin, a member of the inhibitor of apoptosis (IAP) family, expressed during embryonic development while absent in most normal adult cells, is upregulated in a variety of human cancers; its expression in tumors is associated with a more aggressive phenotype, decreased survival, and increased resistance to chemotherapy. KLH may enhance immune recognition and may promote an enhanced response. As SVN53-67 is weakly immunogenic in humans, the M57 alteration may lead to greater affinity towards HLA-A*0201 and thus an enhanced antitumor immune response.
An antibody-drug conjugate (ADC) containing a fully human monoclonal antibody directed against prostate-specific membrane antigen (PSMA), conjugated via a stable, enzyme-cleavable linker to monomethylauristatin E (MMAE), an auristatin derivative and a potent microtubule inhibitor, with potential antineoplastic activity. The monoclonal antibody moiety of this conjugate selectively binds to PSMA, a protein which is abundantly expressed on the surface of metastatic and hormone-refractory prostate cancer cells. Upon internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis.
A ""true human"" (cloned from human B lymphocytes) monoclonal antibody directed against interleukin-1 alpha (IL1a) with potential antineoplastic activity. Anti-IL-1 alpha monoclonal antibody CA-18C3 binds to IL1a and may block the activity of IL1a. IL1a, an inflammatory mediator, plays a key role in interleukin-mediated tumor cell activity such as angiogenesis, tissue matrix remodeling, metastasis and tumor cell invasion.
A chimeric, 25-mer peptide that targets prohibitin, with potential antineoplastic activity. Prohibitin-targeting peptide 1 (prohibitin-TP01) consists of a fat-targeting motif (CKGGRAKDC), two repeats of a proapoptotic peptide motif (KLAKLAK) and a GG linker. This peptide binds specifically to prohibitin in the white adipose vasculature; upon receptor-mediated cell internalization, the ligand/receptor complex triggers apoptosis and results in ablation of white fat. Destruction of white fat may potentially have positive consequences for men with prostate cancer since a high level of white fat has been implicated as a critical contributing factor in poor prostate cancer outcome. Prohibitin, a multifunctional membrane-associated protein that is thought to regulate cell survival and growth, has been shown by immunohistochemical analysis to be expressed in the membrane of endothelial cells in white adipose tissue.
An antibody-drug conjugate (ADC) containing labetuzumab, a mildly reduced, anti-CEACAM5 humanized monoclonal antibody, conjugated to the potent topoisomerase I inhibitor SN-38, with antineoplastic activity. The monoclonal antibody moiety of antibody-drug conjugate IMMU-130 selectively binds to carcinoembryonic cell adhesion molecule 5 (CEACAM5), which is abundantly expressed on the surface of a majority of solid tumors. Upon internalization and proteolytic cleavage, SN-38, the active metabolite of irinotecan, inhibits the activity of topoisomerase I in the tumor cells, eventually inhibiting both DNA replication and transcription and leading to tumor cell apoptosis.
A fully human monoclonal antibody directed against angiopoietin 2 (ANG2) with potential antiangiogenic and antineoplastic activities. Nesvacumab binds to ANG2 and interferes with the interaction between Ang2 and its receptor TEK tyrosine kinase (Tie2), which may inhibit tumor cell angiogenesis and tumor cell proliferation. ANG2 is upregulated in a variety of cancer cell types and plays a crucial role in angiogenesis.
A serotype 3 Dearing strain (T3D) of reovirus (Respiratory Enteric Orphan VIRUS). Reovirus, a dsRNA virus, is able to replicate specifically in cancer cells bearing an activated Ras pathway. In contrast to normal cells, two-thirds of human cancer cells are Ras-activated, and are deficient in their ability to trigger the antiviral response mediated by the host cellular protein, double-stranded RNA-dependent protein kinase (PKR). In Ras-activated cancer cells, reovirus is able to freely replicate and subsequently cause apoptosis in the tumor cells. Cell lysis frees progeny viral particles to infect surrounding cancer cells. This cycle of infection, replication and cell death is believed to be repeated until no more Ras-activated tumor cells are available. Because the reovirus kills Ras-activated cancer cells, this is a potential therapeutic for malignant glioma, pancreatic, colon and some lung cancers.
A finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v6 classification system.
The hydrochloride salt and the z (cis-) stereoisomer of endoxifen with potential antineoplastic activity. Endoxifen, the active metabolite of tamoxifen, competitively inhibits the binding of estradiol to estrogen receptors, thereby preventing the receptor from binding to the estrogen-response element on DNA and thus reducing DNA synthesis. Unlike tamoxifen, however, which relies on CYP2D6 activity for its conversion to the active metabolite endoxifen, the direct administration of endoxifen bypasses the CYP2D6 route. As CYP2D6 activity can vary widely among individuals due to genetic CYP2D6 polymorphisms, endoxifen is therefore theoretically more potent and more uniform in its bioavailability across patient populations.
A gel forming solution containing the maleate salt of timolol, a propanolamine derivative and a non-selective beta-adrenergic antagonist, with intraocular pressure-reducing activity. Although the precise mechanism of action of timolol's ocular hypotensive action is not clearly established at this time, studies suggest that it may be the result of decreased aqueous humor production (possibly by reduction of blood flow to the ciliary processes and cAMP synthesis) as well as a slight increase in outflow facility. Timolol gel-forming solution can potentially be used topically as well, in the prevention of the neoangiogenesis that may occur following pulsed dye laser treatment of port wine stains.
A preparation of autologous CD8+ (cytotoxic) human peripheral blood lymphocytes (PBLs) sensitized to Drosophila cell-presented melanoma peptides, with potential immunostimulating and antineoplastic activities. Autologous CD8+ T-lymphocytes, isolated from a melanoma patient, are exposed in vitro to melanoma peptide-pulsed HLA-A2-expressing Drosophila cells, expanded, and reintroduced into the patient; these tumor-reactive T-cells may stimulate a host immune response against tumor cells expressing the melanoma antigens, resulting in tumor cell lysis. Drosophila cells, which do not express any native MHC molecules, have been shown to potently stimulate tumor-reactivity in vitro from human peripheral blood lymphocytes (PBL) when stably transfected with human MHC molecules and appropriate adhesion and costimulatory molecules.
A gene transfer preparation of a plasmid DNA encoding mouse somatostatin receptor subtype 2 (sst2) and a fusion protein of human deoxycytidine kinase (DCK) and uridine monophosphate kinase (UMK), complexed to a synthetic polycationic carrier, polyethylenimine, with antineoplastic adjuvant application. Upon administration, CYL-02 plasmid DNA expresses DCK::UMK fusion protein that converts gemcitabine into its toxic phosphorylated metabolite. Expression of sst2 protein by this agent could induce both antioncogenic and local antitumor bystander effects. A loss of sst2 gene expression often is found in pancreatic and colorectal cancers, and is the receptor for somatostatin which negatively regulates a number of processes such as epithelial cell proliferation. Combination effects of these gene products allows for less chemotherapy to cause tumor cell lysis in not only the original tumor, but in distant tumors as well.
A metabolite of icariin, a principal flavonoid glycoside in Herba Epimedii (a traditional Chinese medicine herb used in treating osteoporosis) with potential antineoplastic activity. ERa36 modulator icaritin selectively binds to a novel variant of estrogen receptor alpha, a36, and mediates a membrane-initiated ""nongenomic"" signaling pathway, which is linked to activate signaling pathways like the MAPK/ERK and the PI3K/Akt pathways. This agent induces cell cycle arrest at G1, or G2/M arrest depending upon the dose. Consistently with G1 arrest, icaritin increases protein expressions of pRb, p27(Kip1) and p16(Ink4a), while decreasing phosphorylated pRb, Cyclin D1 and CDK4. 40% of ER-negative breast cancer tumors express high levels of ERa36, and this subset of patients is less likely to benefit from tamoxifen treatment compared with those with ERa66-positive/ERa36-negative tumors.
A proprietary fucose-free monoclonal antibody directed against human heparin-binding EGF-like growth factor (HBEGF) with potential antineoplastic activity. Anti-HB-EGF Monoclonal Antibody KHK2866 binds to HBEGF, thereby blocking its binding to the EGF receptors. This prevents EGF receptor activation and the subsequent induction of cell growth signaling. HBEGF is mitogenic for fibroblasts and smooth muscle and may be involved in macrophage-mediated cellular proliferation. The fucose-free monoclonal antibodies enhance antigen dependent cellular cytotoxicity (ADCC), and increase binding affinity to the Fc Receptor to overcome genetic polymorphism.
An optimized small peptide drug candidate targeting epithelial mucin (MUC1) with antineoplastic activity. MUC1-targeted peptide GO-203-2C interacts with oncoprotein MUC1 C-terminal subunit on the cell surface, thereby impeding cell-cell interactions, signaling, and metastasis. MUC1 antigen, a membrane bound glycoprotein expressed by most glandular and ductal epithelial cells, is over-expressed in many diverse human carcinomas including those of the breast, prostate, lung, colon, pancreas, and ovary, and has been associated with poor prognosis.
A recombinant plasmid DNA vaccine containing mammalian expression vector, pUMVC3, encoding epitopes of human Insulin-Like Growth Factor-Binding Protein 2 (hIGFBP-2) with potential antineoplastic activity. Upon vaccination, pUMVC3-hIGFBP-2 multi-epitope plasmid DNA vaccine may produce IGFBP-2 that binds to cell surface, likely via integrin complexes. This results in the dephosphorylation of the focal adhesion-kinase (FAK) and of the p42/44 MAP-kinases, thereby inactivating them; both kinases are involved in cell growth regulation. Furthermore, IGFBP-2 promotes de-adhesion of the cells in a dose-dependent manner, hence impeding cell proliferation. The primary effect of IGFBPs appears to be modulation of IGF activity and control of IGF-mediated cell growth and metabolism.
A viscous, oral hydrogel rinse intended for the management of oral mucositis/stomatitis. Mucoadhesive oral wound rinse consists of purified water, glycerin, benzyl alcohol, sodium saccharin, carbomer homopolymer A, potassium hydroxide, citric acid, polysorbate 60 and phosphoric acid. Upon gargling and rinsing with this solution, it forms a soothing protective hydrogel coating over the oral mucosa, thereby potentially preventing or reducing chemotherapy-induced mucositis.
A dietary supplement containing extract from the medicinal fungus Antrodia cinnamomea with potential antiangiogenic, hepatoprotective and antioxidant activities. The components in Antrodia cinnamomea supplement are rather complex, however, rich in triterpenoids, polysaccharides, nucleosides (adenosine) nucleic acids, superoxide dismutase, other small molecular weight proteins and steroid like compounds. Neutral sugars in this supplement show inhibitory activity on endothelial tube formation, while maleimide and maleic anhydride derivative components in the extract, such as antrodin B and antrodin C and their metabolites, exhibit significant cytotoxic effects on tumor cells and hepatitis C virus.
A humanized IgG4 monoclonal antibody directed against human hepatocyte growth factor receptor (HGFR or c-MET) with potential antineoplastic activity. Anti-c-MET monoclonal antibody LY2875358 binds to c-MET, thereby preventing the binding of HGF to its receptor c-Met and subsequent activation of the HGF/c-Met signaling pathway. This may result in cell death in c-Met-expressing tumor cells. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis.
A fully-human monoclonal antibody directed against human vascular endothelial growth factor receptor 3 (VEGFR-3; Flt-4) with antiangiogenic activity. Anti-VEGFR-3 monoclonal antibody IMC-3C5 specifically binds to and inhibits VEGFR-3, which may result in inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR-3 plays a critical role in the embryonic vascular system development but is restricted postnatally to endothelial cells of lymphatic vessels and found to be expressed in many solid and hematologic malignancies.
A plant-based, proprietary formulation of saliva substitute with potential anti-xerostomia activity. Extracted from the plant called yerba santa (holy herb), herbal polysaccharide saliva substitute contains plant mucins, which is nearly identical to that of human mucous membranes. Upon direct application using the polysaccharide-containing spray, a protective film of moisture is deposited over the mucous membranes of the mouth and throat. The xylitol in this preparation protects against the formation of harmful oral flora and thus helps to prevent cavities. Moreover, this agent has shown a demineralization effect on dentin.
A humanized monoclonal antibody directed against human heparin-binding EGF-like growth factor (HBEGF) with potential antineoplastic activity. Anti-HBEGF monoclonal antibody U3-1565 binds to HBEGF and blocks the binding of HBEGF to the EGF receptors. This prevents EGF receptor activation and the subsequent induction of cell growth signaling. HBEGF is mitogenic for fibroblasts and smooth muscle and may be involved in macrophage-mediated cellular proliferation.
An orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Akt inhibitor LY2780301 binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway, thereby leading to inhibition of cell proliferation and the induction of apoptosis in tumor cells. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
An orally active, selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor GDC-0623 specifically inhibits mitogen-activated protein kinase kinase (MEK or MAP/ERK kinase), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.
A second-generation antisense oligonucleotide targeting the eukaryotic translation initiation factor 4E (eIF4E) with potential antitumor activity. Antisense oligonucleotide ISIS EIF4ERx suppresses the expression of eIF4E in fast dividing tumor cells. Blocking the expression of eIF4E results in inhibition of the synthesis of tumor angiogenic factors, thereby leading to the inhibition of cellular proliferation and apoptosis in tumor cells. eIF4E is overexpressed in a variety of cancers, is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis and is the rate-limiting component of the eukaryotic translation apparatus.
A peptide cancer vaccine consisting of an emulsion of a mixture of 12 class I MHC-restricted melanoma peptides and a class II MHC-restricted tetanus toxoid helper peptide, with potential immunostimulating and antineoplastic activities. Upon administration, the MELITAC 12.1 peptide vaccine may stimulate the host immune system to mount a cytotoxic T-cell response against tumor cells expressing the melanoma peptide antigens, resulting in tumor cell lysis. The melanoma peptides contained in the vaccine are upregulated in melanoma cancer cells.
An adenocarcinoma that arises from the gastric mucosa and is characterized by the presence of isolated malignant cells or malignant cells that form small aggregates. This category includes signet ring cell adenocarcinomas, adenocarcinomas that are composed of malignant cells resembling lymphocytes and histiocytes, and adenocarcinomas that are composed of malignant cells with deeply eosinophilic cytoplasm.
A morphologic finding indicating the presence of a malignant cellular infiltrate characterized by the presence of individual cells and/or tiny cellular aggregates.
A rare adenocarcinoma that arises from the gastric mucosa and is characterized by the presence of large polygonal malignant cells with eosinophilic cytoplasm resembling hepatocytes.
A rare adenocarcinoma that arises from the gastric mucosa and is characterized by the presence of prominent lymphocytic stromal infiltration and poorly formed tubular structures.
A malignant germ cell tumor that arises from the stomach. It is characterized by the presence of syncytiotrophoblast and cytotrophoblast cellular components. It is often associated with lymph node and hematogenous metastases.
Autologous activated T cells that have been coated with bispecific antibodies (BiAb), with potential antineoplastic and immunomodulating activities. In vitro, T cells are activated through exposure to the anti-CD3 murine monoclonal antibody OKT3 and low-dose interleukin 2 (Il-2) for 6-14 days and then armed with anti-CD3 x anti-CD20 bispecific antibody (CD20Bi). Upon administration, anti-CD3 x anti-CD20 bispecific antibody-armed activated T cells (AATC) attach to CD3-expressing T cells and CD20-expressing tumor cells, selectively cross-linking T cells and tumor cells. This may result in the recruitment and activation of cytotoxic T lymphocyte (CTLs), CTL-mediated specific tumor cell lysis, and the secretion of antitumor cytokines and chemokines. CD20, a cell surface phosphoprotein, is found on normal B cells and most B-cell tumors.
A morphologic finding indicating the absence of dysplastic changes in the gastric mucosal epithelium. It includes non-neoplastic inflammatory, reactive, or metaplastic pathologic processes.
A term used to describe an ambiguous morphologic pattern in the gastric mucosa, when there is doubt whether the findings represent a non-neoplastic or neoplastic pathologic process.
A cell-based cancer vaccine composed of autologous, irradiated dendritic cells (DCs) pulsed with ovarian tumor cell lysate containing tumor associated antigens (TAAs) with potential immunostimulatory and antineoplastic activities. Upon administration, autologous ovarian tumor cell lysate-pulsed dendritic cell vaccine may stimulate an anti-tumoral cytotoxic T-lymphocyte (CTL) response against ovarian tumor cells expressing the patients ovarian tumor cell-specific TAAs, which may result in ovarian tumor cell lysis.
A trifunctional bispecific monoclonal antibody with potential antineoplastic activity. FBTA05 contains two antigen-recognition sites: one for human CD3, a T cell surface antigen; and one for human CD20, a tumor-associated antigen that is exclusively expressed on B cells during most stages of B cell development and often overexpressed in B-cell malignancies. In addition, the modified Fc portion of this antibody binds Fc receptors on antigen presenting cells (APCs) such as macrophages and dendritic cells (DCs). FBTA05 brings T cells, CD20-expressing tumor B-cells and APCs together into tricellular complexes, which may result in a potent cytotoxic T-lymphocyte (CTL) response against CD20-expressing tumor B-cells. Fc-mediated binding of APCs in the tricellular complex potentiates CD20 antigen presentation to T cells and the activation of anti-tumor cytotoxic T cells.
A neoplasm that arises from the gastric glandular epithelium and invades the lamina propria but not the submucosa. There is marked glandular crowding, branching and budding, intraluminal necrosis, and prominent mitotic activity. Desmoplastic changes may be present or absent.
An immunoconjugate consisting of a humanized monoclonal antibody against the tumor-associated sialoglycotope CA6 (huDS6) conjugated to the cytotoxic maytansinoid DM4, with potential antineoplastic activity. The anti-CA6 monoclonal antibody moiety of SAR566658 targets and binds to the cell surface antigen CA6. Upon antibody/antigen binding and internalization, the immunoconjugate releases DM4, which binds to tubulin and disrupts microtubule assembly/disassembly dynamics, resulting in inhibition of cell division and cell growth of CA6-expressing tumor cells. The CA6 epitope is found on a variety of solid tumors, including breast, ovarian, cervical, lung and pancreatic tumors.
A non-neoplastic polyp that arises from the stomach. This category includes hyperplastic polyps and hamartomatous polyps.
An Fc engineered, humanized anti-CD19 monoclonal antibody directed against the B-cell-specific membrane protein CD19 with potential immunostimulating and antineoplastic activities. Anti-CD19 monoclonal antibody XmAb5574 targets and binds to CD19, thereby depleting and eliminating CD19-expressing B-cells. The modified Fc region of XmAb5574 increases binding affinity to Fc-gamma receptors of effector cells and thereby enhances antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). CD19 is widely expressed during B-cell development, from pro-B-cell to early plasma cell stages.
A bioadhesive gel containing 10% freeze-dried black raspberries (FBR) with potential chemopreventive and antioxidant activities. The four main constituent black raspberry anthocyanins that contribute significantly to the chemopreventive effects are cyanidin 3-glucoside (C3GLU), cyanidin 3-rutinoside (C3RUT), cyanidin 3-sambubioside (C3SAM) and cyanidin 3-(2(G)-xylosyl) rutinoside (C3XRUT). Upon mucosal application, the anthocyanins from the gel penetrate the oral mucosa and are able to modulate expression of certain proapoptotic and terminal differentiation genes, and reduce the expression of epithelial cyclooxygenase-2 (COX-2) protein. In addition, this gel may also reduce vascular densities in the superficial connective tissues.
An autologous dendritic cells (DCs) vaccine targeting prostate cancer with immunostimulating activity. The autologous DC vaccine is prepared via transfecting DCs with mRNAs extracted from primary prostate cancer tissue, and mRNAs of human telomerase reverse transcriptase (hTERT) and survivin. Upon administration, this DC vaccine may elicit a potent cytotoxic T-cell (CTL) response against prostate cancer cells, resulting in tumor cell death. Both hTERT and survivin are essential in neoplastic growth, and are considered to be universal tumor antigens.
A proprietary, miniature biodegradable polymeric matrix containing small-interfering RNAs for the mutated KRAS oncogene, KRASG12D, (siG12D), with potential antitumor activity. Upon intratumoral injection, this siG12D is released locally, thereby preventing translation of KRAS proteins and potentially inhibiting growth of tumor cells overexpressing KRAS. KRAS, a member of the small GTPase superfamily, is mutated in over 90% of human pancreatic ductal adenocarcinomas (PDAC) and is associated with tumor cell proliferation and reduced survival.
A morphologic finding indicating the presence of gastric epithelial cell differentiation in a tissue sample.
A neoplastic polyp that arises from the stomach. It is characterized by the presence of gastric epithelial differentiation. It includes pyloric gland adenomas and foveolar-type adenomas.
The hydrochloride salt of an orally bioavailable synthetic carbothioamide with potential antineoplastic activity. Multitargeted receptor tyrosine kinase inhibitor MP470 binds to mutant forms of the stem cell factor receptor (c-Kit; SCFR), inhibiting clinically relevant mutants of this receptor tyrosine kinase that may be associated with resistance to therapy. In addition, MP470 inhibits activities of other receptor tyrosine kinases, such as c-Met, Ret oncoprotein, and mutant forms of Flt3 and PDGFR alpha, which are frequently dysregulated in variety of tumors. This agent also suppresses the induction of DNA repair protein Rad51, thereby potentiating the activities of DNA damage-inducing agents. Mutant forms of c-Kit are often associated with tumor chemoresistance.
An orally bioavailable multitargeted receptor tyrosine kinase (RTK) inhibitor with potential antiangiogenic and antineoplastic activities. Ponatinib inhibits unmutated and all mutated forms of Bcr-Abl, including T315I, the highly drug therapy-resistant missense mutation of Bcr-Abl. This agent also inhibits other tyrosine kinases including those associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs); in addition, it inhibits the tyrosine kinase receptor TIE2 and FMS-related tyrosine kinase receptor-3 (Flt3). RTK inhibition by ponatinib may result in the inhibition of cellular proliferation and angiogenesis and may induce cell death. Bcr-Abl is a fusion tyrosine kinase encoded by the Philadelphia chromosome.
A morphologic finding indicating the presence of foveolar-type epithelial cells in a tissue sample.
A rare neoplastic polyp that arises from the stomach. It is characterized by the presence of foveolar-type epithelium. It may be seen in patients with familial adenomatous polyposis.
A humanized monoclonal antibody directed against interleukin-13 (IL-13) with anti-asthmatic and anti-inflammatory activities. Anrukinzumab binds to and blocks the activity of IL-13, which may result in the inhibition of IL-13-mediated inflammation. The IL-13 cytokine is an important mediator of allergic inflammation and other inflammatory processes.
A human IgG4 monoclonal antibody targeting the alpha chain of the granulocyte-macrophage colony-stimulating factor receptor (GM-CSF-Ra), with potential immunomodulating activity. Mavrilimumab binds to GM-CSF-Ra and inhibits the GM-CSF-mediated pathway. This may inhibit inflammation. GM-CSF and its receptor are upregulated in a number of autoimmune diseases and play a key role in the activation, differentiation and function of both granulocytes and monocytes.
A highly selective, orally bioavailable small-molecule inhibitor of the HER family of tyrosine kinases with potential antineoplastic activity. Dacomitinib specifically and irreversibly binds to and inhibits human Her-1, Her-2, and Her-4, resulting in the proliferation inhibition and apoptosis of tumor cells that overexpress these receptors.
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v6 classification system. TNM pathologic findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of the primary tumor. TNM pathologic primary tumor findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v6 classification system as they pertain to staging of regional lymph nodes. TNM pathologic regional lymph nodes findings are based on clinical findings supplemented by histopathologic examination of one or more tissue specimens acquired during surgery.
Bladder cancer with invasion into the muscle layer. (from AJCC 6th Ed.)
Bladder cancer with invasion into the superficial muscle layer. (from AJCC 6th Ed.)
Bladder cancer with invasion into the deep muscle layer. (from AJCC 6th Ed.)
Bladder cancer with invasion to the prostate, uterus, vagina, pelvic wall or abdominal wall. (from AJCC 6th Ed.)
Bladder cancer with invasion to the prostate, uterus or vagina. (from AJCC 6th Ed.)
Bladder cancer with metastasis to a single lymph node with a size of 2 cm or less in greatest dimension. Regional lymph nodes are those within the true pelvis. All other lymph nodes are distant lymph nodes.(from AJCC 6th Ed.)
Bladder cancer with metastasis to a single lymph node with a size of more than 2 cm, but not more than 5 cm in greatest dimension or multiple lymph nodes, none more than 5 cm in greatest dimension. Regional lymph nodes are those within the true pelvis. All other lymph nodes are distant lymph nodes. (from AJCC 6th Ed.)
Bladder cancer with metastasis to one or more lymph nodes with a size of more than 5 cm in greatest dimension. Regional lymph nodes are those within the true pelvis. All other lymph nodes are distant lymph nodes. (from AJCC 6th Ed.)
Bladder cancer in which distant metastasis cannot be assessed. (from AJCC 6th Ed.)
A finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v6 classification system.
A peptide cancer vaccine containing nanoparticles of cholesteryl hydrophobized pullulan (CHP) complexed with the cancer-testis antigen NY-ESO-1 protein, with potential immunostimulating and antineoplastic activities. Upon administration, CHP-NY-ESO-1 peptide vaccine IMF-001 may stimulate the host immune system to mount a humoral and cytotoxic T-cell response against tumor cells expressing NY-ESO-1 antigen, resulting in tumor cell lysis. The self-aggregating CHP, composed of a pullulan backbone and cholesterol branches, forms stable colloidal nanoparticles in water. NY-ESO-1, an antigen found in normal testis, is upregulated in various cancers, including bladder, breast, hepatocellular, melanoma, and prostate cancers.
Stage IV maxillary sinus cancer: Stage IV is divided into stages IVA, IVB, and IVC. Stage IVA: cancer has spread to either one lymph node on the same side of the neck as the cancer and the lymph node is larger than 3 centimeters but smaller than 6 centimeters; or, cancer has spread to more than one lymph node anywhere in the neck, and all are 6 centimeters or smaller; cancer is also found in any of the following areas: the maxillary sinus, bones around the maxillary sinus, tissues under the skin, the eye socket, the base of the skull, and the ethmoid sinuses or cancer is found in one or more lymph nodes in the neck, none larger than 6 centimeters, and in any of the following areas: the front of the eye, the skin of the cheek, the base of the skull, behind the jaw, the bone between the eyes, and the sphenoid or frontal sinuses. Stage IVB: cancer has spread to either: one or more lymph nodes larger than 6 centimeters; or the back of the eye, the brain, the base and middle parts of the skull, nerves in the head, and/or the upper part of the throat behind the nose; cancer may also be found in one or more lymph nodes. Stage IVC: cancer has spread to other parts of the body. Stage IV nasal cavity and ethmoid sinus cancer: Stage IV is divided into stages IVA, IVB, and IVC. Stage IVA: cancer has spread to either one lymph node on the same side of the neck as the cancer and the lymph node is larger than 3 centimeters but smaller than 6 centimeters; or, cancer has spread to more than one lymph node anywhere in the neck, and all are 6 centimeters or smaller; cancer is also found in any of the following places: the nasal cavity or ethmoid sinus., the eye socket, the maxillary sinus, the roof of the mouth, and the bone between the eyes or cancer is found in one or more lymph nodes in the neck, and the lymph nodes are 6 centimeters or smaller; cancer is also found in any of the following areas: the front of the eye, the skin of the nose or cheek, front parts of the skull, the base of the skull, and the sphenoid or frontal sinuses. Stage IVB: cancer is found in any of the following areas: the back of the eye, the brain, the middle parts of the skull, nerves in the head the upper part of the throat behind the nose and the base of the skull. Cancer may also be found in one or more lymph nodes or cancer is found in a lymph node that is larger than 6 centimeters. Stage IVC: cancer has spread to other parts of the body (from PDQ).
A psychotic disorder characterized by prominent hallucinations or delusions that have been determined to be etiologically linked to substance use, intoxication or withdrawal.
Stage II includes: T2, N0, M0. T2: Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: IIIA: (T1/T2, N1a/N1b, M0); IIIB: (T1/T2, N2a/N2b, M0); IIIC: (T1/T2, N2c, M0). T1: Invasive vulvar cancer confined to the vulva or perineum. T2: Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement). N1a: Vulvar cancer with one or two lymph node metastasis each measuring 5 mm or less. N1b: Vulvar cancer with one lymph node metastasis measuring 5 mm or greater. N2a: Vulvar cancer with three or more lymph node metastases each measuring 5 mm or less. N2b: Vulvar cancer with two or more lymph node metastases measuring 5 mm or greater. N2c: Vulvar cancer with lymph node metastasis with extracapsular spread. M0: No distant metastasis. (AJCC 7th ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ (preinvasive carcinoma). N0: No regional lymph node metastasis. M0: No distant metastasis. FIGO no longer includes stage 0. (AJCC 7th ed.)
Dysplasia in the erythroid lineage, which presents with a variety of morphological changes in the bone marrow, including nuclear budding or irregular nuclear contour in erythroblasts. In peripheral blood. [PMID:26791933]
Stage I includes: T1, N0, M0. T1: Invasive vulvar cancer confined to the vulva or perineum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: (T4, Any N, M0); (Any T, N3, M0); (Any T, Any N, M1). T4: Tumor invades other adjacent structures. cN3: Palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral. pN3: Extranodal extension of lymph node metastasis or pelvic lymph node(s) unilateral or bilateral. M0: No distant metastasis. M1: Distant metastasis (lymph node metastasis outside of the true pelvis in addition to visceral or bone sites). (AJCC 7th ed.)
Stage III includes: IIIA (T3, N0, M0); IIIB (T1-3, N1, M0). T3: Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. T1: Tumor invades lamina propria or muscular layer. T2: Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver. N0: No regional lymph node metastasis. N1: Metastases to nodes along the cystic duct, common bile duct, hepatic artery, and/or portal vein. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage II includes: T2, N0, M0. T2: Tumor invades perimuscular connective tissue; no extension beyond serosa or into liver. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor invades lamina propria or muscular layer. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
An herbal remedy containing the leaves and/or flowering tops of a species of wormwood (Artemisia absinthium) with potential anticachexia activity. Upon oral consumption, Artemisia absinthium may decrease production of pro-inflammatory cytokines such as TNF-alpha. As increased levels of pro-inflammatory cytokines is correlated with decreased appetite and weight loss, Artemisia absinthium may increase appetite and improve weight gain.
Stage II includes: II (T2, N0, M0); IIA (T2a, N0, M0); IIA1 (T2a1, N0, M0); IIA2 (T2a2, N0, M0); IIB (T2b, N0, M0); T2: Cervical carcinoma invades beyond uterus but not to pelvic wall or to lower third of vagina. T2a: Tumor without parametrial invasion. T2a1: Clinically visible lesion 4.0 cm or less in greatest dimension. T2a2: Clinically visible lesion more than 4.0 cm in greatest dimension. T2b: Tumor with parametrial invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
A synthetic flavonoid with vascular targeting properties. Flavone acetic acid exhibits an antiproliferative effect on endothelial cells as a result of a superoxide-dependent mechanism, which induces changes in permeability of the vasculature of the tumor. This agent may stimulate tumor necrosis and promote shunting of blood flow to viable regions of the tumor, increasing their oxygenation and rendering them more susceptible to the antitumor effects of hyperthermia and ionizing radiation. (NCI04)
An immunoconjugate of a humanized murine monoclonal antibody (huN-901) and DMI, a semi-synthetic derivative of the plant-derived ansa macrolide maytansine. The antibody moiety of BB-10901 selectively attaches to CD56 antigen, a neural cell adhesion molecule (NCAM)) expressed on the surface of cells of small cell lung cancer (SCLC) and other neuroendocrine (NE) tumors. Thus, the DMI conjugate is targeted specifically to CD56-expressing tumor cells, where it inhibits tubulin polymerization and assembly, resulting in inhibition of mitosis and cell cycle arrest in the S phase. (NCI04)
A pegylated form of a thermostable and protease resistant peptide targeting human vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antiangiogenic activity. Derived from the 10th type III domain of human fibronectin and one of the natural ligands, pegdinetanib binds to VEGFR-2 and prevents activation of VEGFR-2 by other activating ligands. This may inhibit the growth of new tumor blood vessels.
A humanized monoclonal antibody directed against C-C chemokine receptor 4 (CCR4) with potential anti-inflammatory and antineoplastic activities. Mogamulizumab selectively binds to and blocks the activity of CCR4, which may inhibit CCR4-mediated signal transduction pathways and, so, chemokine-mediated cellular migration and proliferation of T cells, and chemokine-mediated angiogenesis. In addition, this agent may induce antibody-dependent cell-mediated cytotoxicity (ADCC) against CCR4-positive T cells. CCR4, a G-coupled-protein receptor for C-C chemokines such MIP-1, RANTES, TARC and MCP-1, is expressed on the surfaces of some types of T cells, endothelial cells, and some types of neurons. CCR4, also known as CD194, may be overexpressed on adult T-cell lymphoma (ATL) and peripheral T-cell lymphoma (PTCL) cells.
A recombinant humanized monoclonal antibody directed against the insulin-like growth factor 1 receptor (IGF1R) with potential antineoplastic activity. Dalotuzumab binds to membrane-bound IGF1R, preventing binding of the ligand IGF1 and the subsequent triggering of the PI3K/Akt signaling pathway; inhibition of this survival signaling pathway may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. The activation of IGF1R, a tyrosine kinase and a member of the insulin receptor family, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF1R signaling has been highly implicated in tumorigenesis and metastasis.
A fully human monoclonal antibody (mAb) agonist of the cell surface receptor CD40 with potential immunostimulatory and antineoplastic activities. Similar to the CD40 ligand (CD40L or CD154), CD40 agonist monoclonal antibody CP-870,893 binds to CD40 on a variety of immune cell types, triggering the cellular proliferation and activation of antigen-presenting cells (APCs), activating B cells and T cells, and enhancing the immune response; in addition, this agent may activate CD40 present on the surfaces of some solid tumor cells, resulting in apoptosis and decreased tumor growth. CD40, a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on various immune cells, many B-cell malignancies, and some solid tumors, mediating both indirect tumor cell killing through the activation of the immune system and direct tumor cell apoptosis.
A chimeric IgG1 monoclonal antibody against human mesothelin with potential anti-tumor activity. Amatuximab specifically targets mesothelin, a cell surface glycoprotein involved in cell adhesion and overexpressed on many epithelial-derived cancer cells. Upon binding to the mesothelin antigen, amatuximab triggers an antibody dependent cellular cytotoxicity (ADCC)-mediated host immune response against mesothelin-expressing cells, resulting in cell lysis.
A small synthetic molecule and aurora kinase (AK) inhibitor with potential antineoplastic activity. AT9283 selectively binds to and inhibits AKs A and B, which are serine-threonine kinases that play essential roles in mitotic checkpoint control during mitosis. Inhibition of these kinases results in an inhibition of cellular division and proliferation in tumor cells that overexpress AKs.
An agent that has affinity for a receptor and intrinsic activity at that receptor.
A second-generation, orally bioavailable, highly selective small molecule inhibitor of the serine/threonine protein kinase Aurora A kinase with potential antineoplastic activity. Alisertib binds to and inhibits Aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, and inhibition of cell proliferation. Aurora A kinase localizes to the spindle poles and to spindle microtubules during mitosis, and is thought to regulate spindle assembly. Aberrant expression of Aurora kinases occurs in a wide variety of cancers, including colon and breast cancers.
A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. E7080 blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis.
A pan-specific, recombinant, fully human monoclonal antibody directed against human transforming growth factor (TGF) -beta 1, 2 and 3 with potential antineoplastic activity. Fresolimumab binds to and inhibits the activity of all isoforms of TGF-beta, which may result in the inhibition of tumor cell growth, angiogenesis, and migration. TGF-beta, a cytokine often over-expressed in various malignancies, may play an important role in promoting the growth, progression, and migration of tumor cells.
A quinazoline and butenamide derivative that acts as a tyrosine kinase inhibitor of epidermal growth factor receptors (ERBB RECEPTORS) and is used in the treatment of metastatic NON-SMALL CELL LUNG CANCER.
An orally bioavailable small molecule inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Linsitinib selectively inhibits IGF-1R, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Overexpressed in a variety of human cancers, IGF-1R stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis.
An orally bioavailable small molecule inhibitor of c-Met with potential antineoplastic activity. c-Met inhibitor ARQ 197 binds to the c-Met protein and disrupts c-Met signal transduction pathways, which may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met protein, the product of the proto-oncogene c-Met, is a receptor tyrosine kinase also known as hepatocyte growth factor receptor (HGFR); this protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis.
An orally bioavailable synthetic carbothioamide with potential antineoplastic activity. Multitargeted receptor tyrosine kinase inhibitor MP470 binds to mutant forms of the stem cell factor receptor (c-Kit; SCFR), inhibiting clinically relevant mutants of this receptor tyrosine kinase that may be associated with resistance to therapy. In addition, MP470 inhibits activities of other receptor tyrosine kinases, such as c-Met, Ret oncoprotein, and mutant forms of Flt3 and PDGFR alpha, which are frequently dysregulated in variety of tumors. This agent also suppresses the induction of DNA repair protein Rad51, thereby potentiating the activities of DNA damage-inducing agents. Mutant forms of c-Kit are often associated with tumor chemoresistance.
A sterically stabilized, pegylated liposomal formulation containing belotecan, a semi-synthetic analogue of campthotecin with potential antitumor activity. Belotecan inhibits the action of topoisomerase I, an enzyme that produces reversible single-strand breaks in DNA during DNA replication. This agent stabilizes the topoisomerase I and DNA complex, resulting in the inhibition of religation of DNA breaks, inhibition of DNA replication, and apoptotic cell death. The polyethylene glycol coating allows for greater plasma circulation time, thus enhancing the concentration of belotecan at the tumor site. Encapsulation of belotecan preserves the active lactone form, resulting in an increased cytotoxic effect of belotecan.
An androgen receptor (AR) antagonist with potential antineoplastic and anti-androgenic activities. BMS-641988 binds to the androgen receptor in target tissues, thereby preventing androgen-induced receptor activation, and facilitates the formation of inactive complexes that cannot be translocated to the nucleus. This may inhibit androgen-dependent gene expression, subsequently leading to an inhibition of cell growth and apoptosis in AR-expressing cells.
The isethionate salt of an amsacrine analogue with antineoplastic properties. Asulacrine inhibits the enzyme topoisomerase ll, thereby blocking DNA replication and RNA and protein synthesis.
An orally bioavailable hydroxymate inhibitor of histone deacetylase (HDAC) with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities. Givinostat inhibits class I and class II HDACs, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling and an altered pattern of gene expression. At low, nonapoptotic concentrations, this agent inhibits the production of pro-inflammatory cytokines such as tumor necrosis factor- (TNF-), interleukin-1 (IL-1), IL-6 and interferon-gamma. Givinostat has also been shown to activate the intrinsic apoptotic pathway, inducing apoptosis in hepatoma cells and leukemic cells. This agent may also exhibit anti-angiogenic activity, inhibiting the production of angiogenic factors such as IL-6 and vascular endothelial cell growth factor (VEGF) by bone marrow stromal cells.
An aqueous oral mouthwash solution containing the monosodium salt of carbonic acid with alkalinizing and antimucositis activities. Upon introduction into the mouth, the sodium bicarbonate dissociates, forming sodium and bicarbonate ions, which buffer excess hydrogen ion and elevates the oral pH. An alkaline oral environment is less prone to colonization with yeast and aciduric bacteria. In addition, this solution may help relieve mucositis and mucositis-induced pain by diluting human saliva, and cleansing and lubricating mucosal tissues of the mouth, tongue and oropharynx.
A water-soluble prodrug of a cyanoguanidine compound with potential antineoplastic activity. In vivo, teglarinad chloride is rapidly converted into active drug through hydrolytic cleavage of a carbonate ester bond. Although the exact mechanism of action has yet to be fully elucidated, the active drug appears to antagonize nuclear factor-kappa B (NF-kB) transcription, resulting in the induction of tumor cell apoptosis.
The hydrochloride salt form of brostacillin, a synthetic, alpha-bromoacrylic, second-generation minor groove binder (MGB), related to distamycin A, with potential antineoplastic activity. Brostallicin binds to DNA minor groove DNA, after having formed a highly reactive glutathione (GSH)-brostallicin complex in the presence of the enzyme glutathione S-transferase (GST), which is overexpressed in cancer cells; DNA replication and cell division are inhibited, resulting in tumor cell death. Compared to typical MGBs, this agent appears to bind covalently to DNA in a different manner and its activity does not depend on a functional DNA mismatch repair (MMR) mechanism. Accordingly, brostallicin may be effective against MMR-defective tumors that are refractory to various anticancer agents.
An orally bioavailable small molecule with potential antineoplastic activity. Hedgehog antagonist GDC-0449 targets the Hedgehog signaling pathway, blocking the activities of the Hedgehog-ligand cell surface receptors PTCH and/or SMO and suppressing Hedgehog signaling. The Hedgehog signaling pathway plays an important role in tissue growth and repair; aberrant constitutive activation of Hedgehog pathway signaling and uncontrolled cellular proliferation may be associated with mutations in the Hedgehog-ligand cell surface receptors PTCH and SMO.
An orally active diketopiperazine derivative with potential antineoplastic activity. Plinabulin selectively targets and binds to the colchicine-binding site of tubulin, thereby interrupting equilibrium of microtubule dynamics. This disrupts mitotic spindle assembly leading to cell cycle arrest at M phase and blockage of cell division. In addition, plinabulin may also inhibit growth of proliferating vascular endothelial cells, thereby disrupting the function of tumor vasculature that further contributes to a decrease in tumor cell proliferation.
An orally bioavailable, small-molecule, bisindolylmaleimide cell cycle inhibitor with potential antineoplastic activity. MKC-1 and its metabolites inhibit tubulin polymerization, blocking the formation of the mitotic spindle, which may result in cell cycle arrest at the G2/M phase and apoptosis. In addition, this agent has been shown to inhibit the activities of the oncogenic kinase Akt, the mTOR pathway, and importin-beta, a protein essential to the transport of other proteins from the cytosol into the nucleus.
A synthetic peptide sequence of human papillomavirus (HPV) type 16 oncoprotein E6. The E6 oncoprotein is implicated in the tumorigenesis of cervical carcinoma. Vaccination with HPV 16 E6 peptide may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against cells expressing the E6 oncoprotein, resulting in tumor cell lysis.
A synthetic luteinizing hormone releasing hormone (LHRH) identical to or similar to the endogenous hormone. Synthesized in and secreted by the hypothalamus, gonadorelin binds to transmembrane LHRH receptors on pituitary gonadotrophic cells, thereby stimulating synthesis and secretion of gonadotropins. Continuous administration of gonadorelin desensitizes the gonadotrophic cells, a negative feedback effect. This agent can be used in treatment of hypothalamic amenorrhea and evaluation of hypothalamic/pituitary function.
A physical or cognitive mental abnormality caused by maternal alcohol consumption and its toxic effect on the developing embryo during pregnancy.
A neoplastic polyp that arises from the stomach. It is usually associated with intestinal-type differentiation. The presence of high grade dysplasia and a size of more than 2 cm are factors that increase the risk of malignant transformation.
Stage II includes: T2, N0, M0. T2: Lesions have been divided into T2a and T2b. T2a is defined as tumor more than 7 cm but less than or equal to 10 cm in greatest dimension, limited to the kidney. T2b is defined as tumor greater than 10 cm, limited to the kidney. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: (T1 or T2, N1, M0); (T3, N0 or N1, M0). T1: Lesions have been divided into T1a and T1b. T1a is defined as tumor 4 cm or less in greatest dimension, limited to the kidney. T1b is defined as tumor greater than 4 cm but not more than 7 cm in greatest dimension, limited to the kidney. T2: Lesions have been divided into T2a and T2b. T2a is defined as tumor more than 7 cm but less than or equal to 10 cm in greatest dimension, limited to the kidney. T2b is defined as tumor greater than 10 cm, limited to the kidney. T3: Tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota's fascia. Lesions have been divided into T3a, T3b, and T3c. T3a: Tumor grossly extends into the renal vein or its segmental (muscle containing) branches, or tumor invades perirenal and/or renal sinus fat but not beyond Gerota's fascia. T3b: Tumor grossly extends into the vena cava below the diaphragm. T3c: Tumor grossly extends into the vena cava above the diaphragm or invades the wall of the vena cava. N0: No regional lymph node metastasis. N1: Metastasis in regional lymph node(s). M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: (T4, Any N, M0); (Any T, Any N, M1). T4: Tumor invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland). M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage III includes: IIIA (T1-T2, N1/N1c, M0); (T1, N2a, M0); IIIB (T3-T4a, N1/N1c, M0); (T2-T3, N2a, M0); (T1-T2, N2b, M0); IIIC (T4a, N2a, M0); (T3-T4a, N2b, M0); (T4b, N1-N2, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor penetrates to the surface of the visceral peritoneum. T4b: Tumor directly invades or is adherent to other organs or structures. N0: No regional lymph node metastasis. N1: Metastasis in 1-3 regional lymph nodes. N1c: Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional lymph node metastasis. N2: Metastasis in four or more regional lymph nodes. N2a: Metastasis in 4-6 regional lymph nodes. N2b: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: IIA (T3, N0, M0); IIB (T4a, N0, M0); IIC (T4b, N0, M0). T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor penetrates to the surface of the visceral peritoneum. T4b: Tumor directly invades or is adherent to other organs or structures. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: For squamous cell carcinoma: IIIA (T1-2, N2, M0, Any G, Tumor location: Any); (T3, N1, M0, Any G, Tumor location: Any); (T4a, N0, M0, Any G, Tumor location: Any); IIIB (T3, N2, M0, Any G, Tumor location: Any); IIIC (T4a, N1-2, M0, Any G, Tumor location: Any); (T4b, Any N, M0, Any G, Tumor location: Any); (Any T, N3, M0, Any G, Tumor location: Any). For adenocarcinoma: IIIA (T1-2, N2, M0, Any G); (T3, N1, M0, Any G); (T4a, N0, M0, Any G); IIIB (T3, N2, M0, Any G); IIIC (T4a, N1-2, M0, Any G); (T4b, Any N, M0, Any G); (Any T, N3, M0, Any G). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T4a: Resectable tumor invading pleura, pericardium, or diaphragm. T4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage II includes: For squamous cell carcinoma: IIA (T2-3, N0, M0, G1, GX, Tumor location: Upper, middle); (T2-3, N0, M0, G2-3, Tumor location: Lower, X); IIB (T2-3, N0, M0, G2-3, Tumor location: Upper, middle); (T1-2, N1, M0, Any G, Tumor location: Any). For adenocarcinoma: IIA (T2, N0, M0, G3); IIB (T3, N0, M0, Any G); (T1-2, N1, M0, Any G). T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage I includes: For squamous cell carcinoma: IA (T1, N0, M0, G1, GX, Tumor location: Any); IB (T1, N0, M0, G2-3, Tumor location: Any); (T2-3, N0, M0, G1, GX, Tumor location: Lower, X). For adenocarcinoma: IA (T1, N0, M0, G1-2, X); IB (T1, N0, M0, G3); (T2, N0, M0, G1-2, GX). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Stage IV includes: IVA: (T1/T2, N3, M0); (T3, Any N, M0); IVB: (Any T, Any N, M1). T1: Invasive vulvar cancer confined to the vulva or perineum. T2: Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal 1/3 urethra, lower/distal 1/3 vagina, anal involvement). T3: Vulvar cancer with tumor of any size with extension to any of the following: upper/proximal 2/3 urethra, upper/proximal 2/3 vagina, bladder mucosa, rectal mucosa, or fixed to pelvic bone. N3: Vulvar cancer with fixed or ulcerated regional lymph node metastasis. M1: distant metastasis (including pelvic lymph node metastasis). (AJCC 7th ed.)
Stage III includes: IIIA : (T0, N2, M0); (T1, N2, M0); (T2, N2, M0); (T3, N1, M0); (T3, N2, M0), IIIB: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0), and IIIC: (any T, N3, M0). T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules). N2: Metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted; or in clinically detected ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases. N3: Metastases in ipsilateral infraclavicular (level III) axillary lymph nodes(s) with or without level I, II axillary lymph node involvement; or in clinically detected ipsilateral internal mammary lymph node(s) with clinically evident level I, II axillary lymph node metastases; or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. M0: No clinical or radiographic evidence of distant metastasis. M0 includes M0(i+). (AJCC 7th Ed.)
A tumor-associated melanocytic differentiation antigen. Vaccination with MART-1 antigen may stimulate a host cytotoxic T-cell response against tumor cells expressing the melanocytic differentiation antigen, resulting in tumor cell lysis. (NCI04)
An initial set of movements by the fetus that is observed by the pregnant mother.
Increased concentration of thiosulfate(2-) in the urine.
Autosomal dominant limb-girdle muscular dystrophy is characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and can range from the first to the sixth decade, although later onset is less common. Most patients present with proximal muscle weakness that progresses to distal involvement, but some can present with distal impairment. The severity is variable: patients with a more severe phenotype can lose ambulation after several decades and have facial weakness with bulbar and respiratory involvement. Muscle biopsy shows dystrophic changes with protein aggregates, myofibrillar degeneration, and rimmed vacuoles (summary by Ruggieri et al., 2015). Genetic Heterogeneity of Autosomal Dominant Limb-Girdle Muscular Dystrophy Other forms of autosomal dominant LGMD include LGMDD2 (608423), previously LGMD1F, caused by mutation in the TNPO3 gene (610032) on chromosome 7q32; LGMDD3 (609115), previously LGMD1G, caused by mutation in the HNRNPDL gene (607137) on chromosome 4q21; and LGMDD4 (618129), previously LGMD1I, caused by mutation in the CAPN3 gene (114240) on chromosome 15q15. For a discussion of autosomal recessive LGMD, see 253600.
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs with onset in childhood.
KCNQ2-related disorders represent a continuum of overlapping neonatal epileptic phenotypes caused by a heterozygous pathogenic variant in KCNQ2. The clinical features of KCNQ2-related disorders range from KCNQ2-related benign familial neonatal epilepsy (KCNQ2-BFNE) at the mild end to KCNQ2-related neonatal epileptic encephalopathy (KCNQ2-NEE) at the severe end. KCNQ2-BFNE is characterized by a wide spectrum of seizure types (tonic or apneic episodes, focal clonic activity, or autonomic changes) that start in otherwise healthy infants between the second and eighth day of life and spontaneously disappear between the first and the sixth to twelfth month of life. Motor activity may be confined to one body part, migrate to other body regions, or generalize. Seizures are generally brief, lasting one to two minutes. Rarely, KCNQ2-BFNE may evolve into status epilepticus. About 10%-15% of individuals with BFNE develop epileptic seizures later in life. KCNQ2-NEE is characterized by multiple daily seizures beginning in the first week of life that are mostly tonic, with associated focal motor and autonomic features. Seizures generally cease between ages nine months and four years. At onset, EEG shows a burst-suppression pattern or multifocal epileptiform activity; early brain MRI can show basal ganglia and thalamic hyperintensities that later resolve. Moderate to severe developmental impairment is present.
A reduction in the activity of the mitochondrial respiratory chain complex III, which is part of the electron transport chain in mitochondria.
Aarskog syndrome is characterized by short stature and facial, limb, and genital anomalies. One form of the disorder is X-linked (see 305400), but there is also evidence for autosomal dominant and autosomal recessive (227330) inheritance (summary by Grier et al., 1983).
A benign epithelial neoplasm composed of layers of oncocytes (small round nucleus, micro-granular, eosinophilic cytoplasm with numerous tightly-packed mitochondria.
16p12.2 recurrent deletion is characterized by variable clinical findings that do not constitute a recognizable syndrome. Of note, the significant bias in ascertainment of individuals undergoing clinical chromosomal microarray analysis (i.e., children with intellectual disability and developmental delay; individuals with schizophrenia) makes it difficult to accurately associate specific phenotypes with the 16p12.2 recurrent deletion. Findings commonly observed in children (probands) with this deletion include: developmental delay, cognitive impairment (ranging from mild to profound), growth impairment (including short stature), cardiac malformations, epilepsy, and psychiatric and/or behavioral problems. Other findings can include: hearing loss, dental abnormalities, renal and genital anomalies (the latter in males), and cleft palate ± cleft lip.
Common variable immunodeficiency (CVID) is a clinically and genetically heterogeneous group of disorders characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections, and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B cells are usually in the normal range, but can be low. Most individuals with CVID have onset of infections after age 10 years. CVID represents the most common form of primary immunodeficiency disorders and is the most common form of primary antibody deficiency. Approximately 10 to 20% of patients with a diagnosis of CVID have a family history of the disorder (reviews by Chapel et al., 2008, Conley et al., 2009, and Yong et al., 2009). Genetic Heterogeneity of Common Variable Immunodeficiency Common variable immunodeficiency is a genetically heterogeneous disorder. See also CVID2 (240500), caused by mutation in the TACI gene (TNFRSF13B; 604907); CVID3 (613493), caused by mutation in the CD19 gene (107265); CVID4 (613494), caused by mutation in the BAFFR gene (TNFRSF13C; 606269); CVID5 (613495), caused by mutation in the CD20 gene (112210); CVID6 (613496), caused by mutation in the CD81 gene (186845); CVID7 (614699), caused by mutation in the CD21 gene (CR2; 120650); CVID8 (614700), caused by mutation in the LRBA gene (606453); CVID10 (615577), caused by mutation in the NFKB2 gene (164012); CVID11 (615767), caused by mutation in the IL21 gene (605384); CVID12 (616576), caused by mutation in the NFKB1 gene (164011); CVID13 (616873), caused by mutation in the IKZF1 gene (603023); and CVID14 (617765), caused by mutation in the IRF2BP2 gene (615332). The disorder formerly designated CVID9 has been found to be a form of autoimmune lymphoproliferative disorder; see ALPS3 (615559).
Keloid is a dermal fibroproliferative growth caused by pathologic wound healing following skin injury. Keloid is defined as a scar growing continuously and invasively beyond the confines of the original wound and is characterized by excessive fibroblast proliferation and deposition of extracellular matrix and collagen fibers. Local tissue factors, especially wound tension or infection, and endocrine factors are known to be involved in keloid formation. However, the fact that the incidence of keloid is higher in darker-skinned individuals suggests that genetic factors also play an important role (summary by Nakashima et al., 2010).
Myotonia caused by mutations of the SCN4A gene, resulting in sodium muscle channelopathy. It is characterized by severe episodes of laryngospasm in the neonatal period, which can be alleviated by channel blockers.
Melorheostosis (MEL) is characterized by 'flowing' hyperostosis of the cortex of tubular bones. The lesions are usually asymmetric and involve only 1 limb or correspond to a particular sclerotome. They may be accompanied by abnormalities of adjacent soft tissue, including joint contractures, sclerodermatous skin lesions, muscle atrophy, or hemangiomas (review by Hellemans et al., 2004). The designation combines root words meaning 'limb,' 'flow,' and 'bone.' Melorheostosis may sometimes be a feature of Buschke-Ollendorff syndrome (BOS; 166700), a benign disorder which is caused by mutation in the LEMD3 gene (607844). Although germline or somatic LEMD3 mutations had been postulated to cause isolated melorheostosis (Butkus et al., 1997; Debeer et al., 2003; Happle, 2004; Hellemans et al., 2004), several studies have not been able to prove this (Hellemans et al., 2004; Mumm et al., 2007; Zhang et al., 2009).
The Passovoy factor defect was originally described as an autosomal dominant bleeding disorder characterized by a prolonged activated partial thromboplastin time (APTT) (Hougie et al., 1975). However, further characterization of supposedly affected individuals has identified other causes for the prolonged APTT, thus casting doubt on the existence of the Passovoy factor defect as a distinct entity (Foster et al., 1992; Hayani et al., 1996).
TK2-related mitochondrial DNA (mtDNA) maintenance defect is a phenotypic continuum that ranges from severe to mild. To date, approximately 107 individuals with a molecularly confirmed diagnosis have been reported. Three main subtypes of presentation have been described: Infantile-onset myopathy with neurologic involvement and rapid progression to early death. Affected individuals experience progressive muscle weakness leading to respiratory failure. Some individuals develop dysarthria, dysphagia, and/or hearing loss. Cognitive function is typically spared. Juvenile/childhood onset with generalized proximal weakness and survival to at least 13 years. Late-/adult-onset myopathy with facial and limb weakness and mtDNA deletions. Some affected individuals develop respiratory insufficiency, chronic progressive external ophthalmoplegia, dysphagia, and dysarthria.
Partial dislocation of the head of the radius in the posterior direction.
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs with congenital onset recognizable at birth.
Blount disease is a developmental condition characterized by disordered endochondral ossification of the medial part of the proximal tibial physis resulting in multiplanar deformities of the lower limb (review by Sabharwal, 2009).
A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.
The 16p11.2 recurrent microdeletion phenotype is characterized by developmental delay, intellectual disability, and/or autism spectrum disorder (ASD). Developmental delays are related to diminished language, cognitive function, and motor impairments. While IQ scores range from mild intellectual disability to normal, those with IQ scores in the average range typically have other developmental issues such as language delay or ASD. Expressive language appears to be more affected than receptive language. Seizures are observed in approximately 20% of individuals with the recurrent microdeletion. Macrocephaly is common, usually becoming apparent by age two years. Chiari malformations/cerebellar ectopia are the most frequently observed structural brain abnormalities. In individuals with the 16p11.2 recurrent microdeletion the frequency of birth defects of all types is slightly increased, with vertebral anomalies appearing to be most frequent.
Lack of production of either functional C1r or C1s protein, due to a genetic defect. Approximately 60% of patients with a C1r/C1s deficiency will develop a severe systemic lupus erythematosus at an early age. Patients also present with frequent sinopulmonary infections often with Streptococcus pneumoniae.
Complement component 2 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses. People with complement component 2 deficiency have a significantly increased risk of recurrent bacterial infections, specifically of the lungs (pneumonia), the membrane covering the brain and spinal cord (meningitis), and the blood (sepsis), which may be life-threatening. These infections most commonly occur in infancy and childhood and become less frequent in adolescence and adulthood.Complement component 2 deficiency is also associated with an increased risk of developing autoimmune disorders such as systemic lupus erythematosus (SLE) or vasculitis. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. Between 10 and 20 percent of individuals with complement component 2 deficiency develop SLE. Females with complement component 2 deficiency are more likely to have SLE than affected males, but this is also true of SLE in the general population.The severity of complement component 2 deficiency varies widely. While some affected individuals experience recurrent infections and other immune system difficulties, others do not have any health problems related to the disorder.
Aicardi-Goutières syndrome is a disorder that mainly affects the brain, the immune system, and the skin.Most newborns with Aicardi-Goutières syndrome do not show any signs or symptoms of the disorder. However, about 20 percent are born with a combination of features that include an enlarged liver and spleen (hepatosplenomegaly), elevated blood levels of liver enzymes, a shortage of blood cell fragments called platelets that are needed for normal blood clotting (thrombocytopenia), and neurological abnormalities. While this combination of signs and symptoms is typically associated with the immune system's response to a viral infection that is present at birth (congenital), no actual infection is found in these infants. For this reason, Aicardi-Goutières syndrome is sometimes referred to as a ""mimic of congenital infection.""Within the first year of life, most individuals with Aicardi-Goutières syndrome experience an episode of severe brain dysfunction (encephalopathy), typically lasting for several months. During this encephalopathic phase of the disorder, affected babies are usually extremely irritable and do not feed well. They may develop intermittent fevers in the absence of infection (sterile pyrexias) and may have seizures. They stop developing new skills and begin losing skills they had already acquired (developmental regression). Growth of the brain and skull slows down, resulting in an abnormally small head size (microcephaly). In this phase of the disorder, white blood cells and other immune system molecules associated with inflammation can be detected in the cerebrospinal fluid, which is the fluid that surrounds the brain and spinal cord (central nervous system). These abnormal findings are consistent with inflammation and tissue damage in the central nervous system.The encephalopathic phase of Aicardi-Goutières syndrome causes permanent neurological damage that is usually severe. Medical imaging reveals loss of white matter in the brain (leukodystrophy). White matter consists of nerve fibers covered by myelin, which is a substance that protects nerves and insures rapid transmission of nerve impulses. Affected individuals also have abnormal deposits of calcium (calcification) in the brain. As a result of this neurological damage, most people with Aicardi-Goutières syndrome have profound intellectual disability. They also have muscle stiffness (spasticity); involuntary tensing of various muscles (dystonia), especially those in the arms; and weak muscle tone (hypotonia) in the torso.Some people with Aicardi-Goutières syndrome have features characteristic of autoimmune disorders, which occur when the immune system malfunctions and attacks the body's own systems and organs. Some of these features overlap with those of another disorder called systemic lupus erythematosus (SLE). A feature of SLE that also occurs in about 40 percent of people with Aicardi-Goutières syndrome is a skin problem called chilblains. Chilblains are painful, itchy skin lesions that are puffy and red, and usually appear on the fingers, toes, and ears. They are caused by inflammation of small blood vessels, and may be brought on or made worse by exposure to cold. Vision problems, joint stiffness, and mouth ulcers are other features that can occur in both disorders.As a result of the severe neurological problems usually associated with Aicardi-Goutières syndrome, most people with this disorder do not survive past childhood. However, some affected individuals who develop the condition later or have milder neurological problems live into adulthood.
Hexokinase deficiency is an autosomal recessive disorder characterized by early-onset severe hemolytic anemia (summary by van Wijk et al., 2003).
An increased concentration of prostaglandin E2 in the blood.
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of DAG1 (128239), collectively known as 'dystroglycanopathies' (van Reeuwijk et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
MDDGB3 is an autosomal recessive congenital muscular dystrophy with mental retardation and mild brain abnormalities (Clement et al., 2008). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Mercuri et al., 2009). For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of DAG1 (128239), collectively known as 'dystroglycanopathies' (Beltran-Valero de Bernabe et al., 2004). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of DAG1 (128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Congenital muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) are characterized by early onset of muscle weakness, usually before ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; Godfrey et al., 2007). Congenital muscular dystrophy-dystroglycanopathies with or without mental retardation (type B) represent the intermediate range of the spectrum of dystroglycanopathies. They are less severe than muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and more severe than limb-girdle muscular dystrophy-dystroglycanopathy (type C; see MDDGC1, 609308). Genetic Heterogeneity of Congenital Muscular Dystrophy-Dystroglycanopathy with or without Mental Retardation (Type B) Congenital muscular dystrophy with mental retardation due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGB2 (613156), caused by mutation in the POMT2 gene (607439); MDDGB3 (613151), caused by mutation in the POMGNT1 gene (606822); MDDGB4 (613152), caused by mutation in the FKTN gene (607440); MDDGB5 (616612), caused by mutation in the FKRP gene (606596); MDDGB6 (608840), caused by mutation in the LARGE gene (603590); and MDDGB14 (615351), caused by mutation in the GMPPB gene (615320).
MDDGB2 is an autosomal recessive congenital muscular dystrophy associated with mental retardation and mild structural brain abnormalities (Yanagisawa et al., 2007). It is part of a group of similar disorders, collectively known as 'dystroglycanopathies,' resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) (Godfrey et al., 2007). For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
MDDGC3 is a rare form of autosomal recessive limb-girdle muscular dystrophy with normal cognition (Clement et al., 2008). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
MDDGC2 is an autosomal recessive muscular dystrophy with onset after ambulation is achieved. Cognition is normal (Biancheri et al., 2007). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
Pseudopili annulati is an unusual variant of normal hair characterized by a banded appearance of the hair under reflective light, as observed in pili annulati (180600), but resulting from a distinct underlying physical defect. There is no increased hair fragility (Price et al., 1970).
An abnormality of the humoral immune system, which comprises antibodies produced by B cells as well as the complement system.
Handigodu disease is a autosomal dominant spondyloepimetaphyseal dysplasia prevalent in a few villages of 2 districts of the state of Karnataka in southern India (Agarwal et al., 1994).
Digits that appear disproportionately long compared to the foot.
Reduced strength of the distal musculature of the arms.
Non-alcoholic fatty liver disease (NAFLD) is a buildup of excessive fat in the liver that can lead to liver damage resembling the damage caused by alcohol abuse, but that occurs in people who do not drink heavily. The liver is a part of the digestive system that helps break down food, store energy, and remove waste products, including toxins. The liver normally contains some fat; an individual is considered to have a fatty liver (hepatic steatosis) if the liver contains more than 5 to 10 percent fat.The fat deposits in the liver associated with NAFLD usually cause no symptoms, although they may cause increased levels of liver enzymes that are detected in routine blood tests. Some affected individuals have abdominal pain or fatigue. During a physical examination, the liver may be found to be slightly enlarged.Between 7 and 30 percent of people with NAFLD develop inflammation of the liver (non-alcoholic steatohepatitis, also known as NASH), leading to liver damage. Minor damage to the liver can be repaired by the body. However, severe or long-term damage can lead to the replacement of normal liver tissue with scar tissue (fibrosis), resulting in irreversible liver disease (cirrhosis) that causes the liver to stop working properly. Signs and symptoms of cirrhosis, which get worse as fibrosis affects more of the liver, include fatigue, weakness, loss of appetite, weight loss, nausea, swelling (edema), and yellowing of the skin and whites of the eyes (jaundice). Scarring in the vein that carries blood into the liver from the other digestive organs (the portal vein) can lead to increased pressure in that blood vessel (portal hypertension), resulting in swollen blood vessels (varices) within the digestive system. Rupture of these varices can cause life-threatening bleeding.NAFLD and NASH are thought to account for many cases of cirrhosis that have no obvious underlying cause (cryptogenic cirrhosis); at least one-third of people with NASH eventually develop cirrhosis. People with NAFLD, NASH, and cirrhosis are also at increased risk of developing liver cancer (hepatocellular cancer).NAFLD is most common in middle-aged or older people, although younger people, including children, are also affected. It is often considered as part of a group of conditions known collectively as the metabolic syndrome; in addition to NAFLD, the metabolic syndrome includes obesity, type 2 diabetes or pre-diabetes (insulin resistance), high levels of fats (lipids) such as cholesterol and triglycerides in the blood, and high blood pressure (hypertension). However, a person with NAFLD may not have all or any of the other conditions that make up the metabolic syndrome, and individuals with some or all of those conditions may not have NAFLD.
Warsaw breakage syndrome is a condition that can cause multiple abnormalities. People with Warsaw breakage syndrome have intellectual disability that varies from mild to severe. They also have impaired growth from birth leading to short stature and a small head size (microcephaly). Affected individuals have distinctive facial features that may include a small forehead, a short nose, a small lower jaw, a flat area between the nose and mouth (philtrum), and prominent cheeks. Other common features include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and heart malformations.
Microcephaly, seizures, and developmental delay is an autosomal recessive neurodevelopmental disorder with onset in infancy. There is a range of phenotypic severity: some patients have a disease course consistent with early infantile epileptic encephalopathy (EIEE), whereas others have more well-controlled seizures and a protracted course associated with cerebellar atrophy and peripheral neuropathy (Shen et al., 2010 and Poulton et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of heterogeneity of autism, see 209850.
Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness in which all other visual functions, including visual acuity, visual field, and color vision, are usually normal. A typical feature of the disease is a golden or gray-white discoloration of the fundus that disappears in the dark-adapted state and reappears shortly after the onset of light (Mizuo phenomenon). The course of dark adaptation of rod photoreceptors is extremely retarded, whereas that of cones appears to proceed normally (summary by Fuchs et al., 1995). For a general description and a discussion of genetic heterogeneity of Oguchi disease, see CSNBO1 (258100).
The deletion of a 220-kb region on chromosome 16p11.2 encompassing approximately 9 genes, including the SH2B1 gene (608937), is associated with a highly penetrant form of isolated severe early-onset obesity as well as obesity with developmental delay (summary by Bachmann-Gagescu et al., 2010). An extended 1.7-Mb deletion of chromosome 16p11.2 containing both the 220-kb region and the proximal 593-kb region associated autism (see 611913) has been reported in 2 patients with a syndrome of autism, mental retardation, and obesity and in 2 patients with pervasive developmental disorder, auditory processing difficulties, and attention deficit-hyperactivity disorder but not obesity. For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see 606641.
The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT; 312750), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by mutation in the MECP2 gene (300005).
Glucose phosphate isomerase (GPI) deficiency is an inherited disorder that affects red blood cells, which carry oxygen to the body's tissues. People with this disorder have a condition known as chronic hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, resulting in a shortage of red blood cells (anemia). Chronic hemolytic anemia can lead to unusually pale skin (pallor), yellowing of the eyes and skin (jaundice), extreme tiredness (fatigue), shortness of breath (dyspnea), and a rapid heart rate (tachycardia). An enlarged spleen (splenomegaly), an excess of iron in the blood, and small pebble-like deposits in the gallbladder or bile ducts (gallstones) may also occur in this disorder.Hemolytic anemia in GPI deficiency can range from mild to severe. In the most severe cases, affected individuals do not survive to birth. Individuals with milder disease can survive into adulthood. People with any level of severity of the disorder can have episodes of more severe hemolysis, called hemolytic crises, which can be triggered by bacterial or viral infections.A small percentage of individuals with GPI deficiency also have neurological problems, including intellectual disability and difficulty with coordinating movements (ataxia).
Autosomal recessive isolated posterior microphthalmos defines a rare distinct phenotype restricted to the posterior segment of the eye. In adults, it is clinically characterized by extreme hyperopia (from +7.5 to +21 diopters) due to short axial length (14 mm to 20 mm; normal is greater than 21 mm). Other features include an essentially normal anterior segment, steep corneal curvatures, shallow anterior chamber, thick lenses, and thickened scleral wall. The palpebral fissures appear narrow because of relatively deep-set eyes, visual acuity is mildly to moderately reduced, and anisometropic or strabismic amblyopia is common. The fundus of the eye shows crowded optical discs, tortuous vessels, and an abnormal foveal avascular zone; in addition, papillomacular folds are often reported. Morphometric features of the small eyes predispose to complications such as narrow-angle glaucoma and uveal effusion (summary by Gal et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of isolated microphthalmia, see MCOP1 (251600).
The 8p11 myeloproliferative syndrome is a rare aggressive condition characterized in its typical form by the occurrence, either simultaneously or sequentially, of a BCR/ABL-negative myeloproliferative disorder and a lymphoma, usually a precursor T-lymphoblastic lymphoma. The disease most often terminates in acute myeloid leukemia (Goradia et al., 2008).
Limb-girdle muscular dystrophy type 1H (LGMD1H) is an autosomal dominant disorder characterized by adult onset of progressive proximal muscle weakness affecting both the upper and lower limbs (Bisceglia et al., 2010). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511).
The cardinal features of chromosome 6q11-q14 interstitial deletions include hypotonia, short stature, skeletal/limb anomalies, umbilical hernia, and urinary tract anomalies, as well as characteristic facial features including upslanting palpebral fissures, low-set and/or dysplastic ears, and high-arched palate (summary by Wang et al., 2009).
Macrostomia is a congenital defect resulting from persistent lateral facial clefts, caused by failure of the maxillary and mandibular portions of the first branchial arch to unite normally. Macrostomia is a rare anomaly, with an estimated incidence of 1 in 150,000 to 300,000 births and is most often associated with other anomalies. Unilateral macrostomia is more common than bilateral (summary by Hawkins et al., 1973).
Myopathy, lactic acidosis, and sideroblastic anemia-2 is an autosomal recessive disorder of the mitochondrial respiratory chain. The disorder shows marked phenotypic variability: some patients have a severe multisystem disorder from infancy, including cardiomyopathy and respiratory insufficiency resulting in early death, whereas others present in the second or third decade of life with sideroblastic anemia and mild muscle weakness (summary by Riley et al., 2013). For a discussion of genetic heterogeneity of MLASA, see MLASA1 (600462).
Noonan syndrome-like disorder is a developmental disorder resembling Noonan syndrome (NS1; 163950) and characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, and ectodermal and musculoskeletal anomalies. There is extensive phenotypic heterogeneity and variable expressivity (summary by Martinelli et al., 2010). Patients with heterozygous germline CBL mutations have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia (JMML; 607785), as also seen in patients with Noonan syndrome (summary by Niemeyer et al., 2010).
Ectodermal dysplasia-syndactyly syndrome (EDSS) is characterized by sparse to absent scalp hair, eyebrows, and eyelashes, hypoplastic nails, tooth enamel hypoplasia, conical-shaped teeth, palmoplantar keratoderma, and partial cutaneous syndactyly (summary by Raza et al., 2015). Genetic Heterogeneity of Ectodermal Dysplasia-Syndactyly Syndrome Ectodermal dysplasia-syndactyly syndrome-2 (EDSS2; 613576) maps to chromosome 7p21-p14.
Occult macular dystrophy is characterized by progressive decline of visual acuity in both eyes, associated with a normal fundus and normal fluorescein angiography. Patients have normal full-field electroretinograms (ERGs) but severely reduced focal macular ERGs, as recorded by conventional techniques using small stimuli under background illumination. OCMD patients are believed to have localized retinal dysfunction distal to the ganglion cells in the central retina (summary by Piao et al., 2000).
Torsade de pointes is characterized by an electrocardiographic (ECG) pattern of nonuniform but still-organized electrical activity with progressive changes in morphology, amplitude, and polarity of the QRS complexes, the peaks of which twist around the isoelectric baseline before ending spontaneously. In classic torsade de pointes, the coupling interval of the first beat is long (see LQT1, 192500), whereas in this short-coupled variant, the coupling interval of the first beat is very short (summary by Leenhardt et al., 1994).
Electrocardiographic (ECG) early repolarization, defined as an elevation of the QRS-ST junction (J-point) of at least 1.0 mm (0.1 mV) from baseline in the inferior or lateral lead, manifest as QRS slurring or notching, is a common ECG finding that is generally considered to be benign but may be associated with ventricular fibrillation in some patients (summary by Haissaguerre et al., 2008).
The chromosome 16p12.2-p11.2 deletion syndrome is characterized phenotypically by dysmorphic facial features, feeding difficulties, recurrent ear infections, developmental delay, and cognitive impairment. Additional features, such as heart defects and short stature, are variable (Ballif et al., 2007; Battaglia et al., 2009). The pericentric region of chromosome 16, specifically involving 16p12-p11, is a structurally complex region enriched in repetitive sequence elements, rendering this region susceptible to deletion or rearrangement (Ballif et al., 2007). There are several phenotypes associated with variation in this region: see 611913 for a deletion or duplication at 16p11.2 associated with autism; see 136570 for discussion of a recurrent 520-kb deletion at 16p12.1 associated with developmental delay and craniofacial dysmorphism; and see 613444 for a 220-kb deletion at 16p11.2 associated with isolated severe early-onset obesity and obesity with developmental delay. Battaglia et al. (2009) emphasized that the region at chromosome 16p11.2 that confers susceptibility to autism (AUTS14; see 611913) is located more centromeric to and is distinct from the 16p12.2-p11.2 region involved in the multiple congenital anomalies and intellectual disability phenotype.
COG5-congenital disorder of glycosylation (COG5-CDG, formerly known as congenital disorder of glycosylation type IIi) is an inherited condition that causes neurological problems and other abnormalities. The pattern and severity of this disorder's signs and symptoms vary among affected individuals.Individuals with COG5-CDG typically develop signs and symptoms of the condition during infancy. These individuals often have weak muscle tone (hypotonia) and delayed development. Other neurological features include moderate to severe intellectual disability, poor coordination, and difficulty walking. Some affected individuals never learn to speak. Other features of COG5-CDG include short stature, an unusually small head size (microcephaly), and distinctive facial features, which can include ears that are set low and rotated backward, a short neck with a low hairline in the back, and a prominent nose. Less commonly, affected individuals can have hearing loss caused by changes in the inner ear (sensorineural hearing loss), vision impairment, damage to the nerves that control bladder function (a condition called neurogenic bladder), liver disease, and joint deformities (contractures).
Primary hyperoxaluria is an autosomal recessive disorder of glyoxylate metabolism that results in excessive endogenous oxalate synthesis and the formation of calcium oxalate kidney stones. Progressive renal inflammation and interstitial fibrosis from advanced nephrocalcinosis, recurrent urolithiasis, and urinary tract infections can cause reduced renal function, systemic oxalate deposition, and end-stage renal failure. Compared to hyperoxaluria type I (HP1; 259900) and type II (HP2; 260000), HP3 appears to be the least severe, with good preservation of kidney function in most patients. The typical clinical characteristic is early onset of recurrent urolithiasis, but less active stone formation later (summary by Wang et al., 2015). For a discussion of genetic heterogeneity of primary hyperoxaluria, see HP1 (259900).
Combined deficiency of factor V (612309) and factor VIII (300841) is characterized by bleeding symptoms similar to those in hemophilia (306700) or parahemophilia (227400), caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma FV and FVIII antigen and activity levels are in the range of 5 to 30%. Inheritance of F5F8D is autosomal recessive and distinct from the coinheritance of FV deficiency and FVIII deficiency (summary by Zhang and Ginsburg, 2004).
An extremely rare syndrome with characteristics of the association of radioulnar synostosis with microcephaly, scoliosis, short stature and intellectual deficit.
The tuberculin skin test (TST), or Mantoux test, measures induration of the skin after intradermal inoculation of M. tuberculosis purified protein derivative and thereby detects M. tuberculosis-infected and -noninfected persons. The TST triggers a classical T cell-mediated delayed-type hypersensitivity reaction against mycobacterial antigens. About 20% of individuals living in areas hyperendemic for tuberculosis show persistent absence of TST reactivity, suggesting T cell-independent resistance to M. tuberculosis infection. Genetic epidemiologic studies in endemic areas have suggested that host genetic factors contribute to resistance to M. tuberculosis infection and to the immune reactions underlying TST reactivity (summary by Cobat et al., 2009).
19p13.13 deletion syndrome is a condition that results from a chromosomal change in which a small piece of chromosome 19 is deleted in each cell. The deletion occurs on the short (p) arm of the chromosome at a position designated p13.13.Features commonly associated with this chromosomal change include an unusually large head size (macrocephaly), tall stature, and intellectual disability that is usually moderate in severity. Many affected individuals have significantly delayed development, including speech, and children may speak few or no words. Weak muscle tone (hypotonia) and problems with coordinating muscle movement (ataxia) contribute to delays in gross motor skills (such as sitting and walking) and fine motor skills (such as holding a pencil).Other signs and symptoms that can occur with 19p13.13 deletion syndrome include seizures, abnormalities of brain structure, and mild differences in facial features (such as a prominent forehead). Many affected individuals have problems with feeding and digestion, including constipation, diarrhea, vomiting, and abdominal pain. Eye problems that can impair vision are also common. These include eyes that do not point in the same direction (strabismus) and underdevelopment of the optic nerves, which carry visual information from the eyes to the brain.The signs and symptoms of 19p13.13 deletion syndrome vary among affected individuals. In part, this variation occurs because the size of the deletion, and the number of genes it affects, varies from person to person.
Spastic paraplegia-48 is an autosomal recessive neurologic disorder characterized by spasticity of the lower limbs resulting in gait difficulties. Most patients have onset in mid- or late-adulthood, although childhood onset has been reported in 1 patient. Additional features may include parkinsonism, urinary incontinence, neuropathy, and mild cognitive impairment (summary by Hirst et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
C1q deficiency is a rare autosomal recessive disorder characterized by recurrent skin lesions, chronic infections, and an increased risk of autoimmune diseases, particularly systemic lupus erythematosus (SLE; see 152700) or SLE-like diseases. It has also been associated with chronic glomerulonephritis and renal failure. C1q deficiency presents in 2 different forms, absent C1q protein or presence of a dysfunctional molecule (summary by Topaloglu et al., 1996 and Vassallo et al., 2007).
Rajab interstitial lung disease with brain calcifications (RILCBC) is an autosomal recessive multisystem disorder with a highly variable phenotype. Most patients present in infancy or early childhood with poor growth and interstitial lung disease, which may lead to death. Some may also have liver, skeletal, and renal abnormalities, and most have intracranial calcifications on brain imaging. Some may have early impaired motor development, but most have normal cognitive development (summary by Xu et al., 2018).
A form of congenital disorders of N-linked glycosylation with characteristics of facial dysmorphism (microcephaly, high forehead, low posterior hairline, strabismus), hypotonia, failure to thrive, intractable seizures, developmental delay, persistent vomiting and gastric bleeding. Additional features that may be observed include fat pads anomalies, inverted nipples, and body temperature oscillation. The disease is caused by mutations in the gene ALG11 (13q14.3).
Congenital dyserythropoietic anemia type IV is an autosomal dominant inherited red blood cell disorder characterized by ineffective erythropoiesis and hemolysis resulting in anemia. Circulating erythroblasts and erythroblasts in the bone marrow show various morphologic abnormalities. Affected individuals with CDAN4 also have increased levels of fetal hemoglobin (summary by Arnaud et al., 2010). For a discussion of genetic heterogeneity of congenital dyserythropoietic anemia, see CDAN1 (224120).
Approximately 5 to 20% of all patients with neurofibromatosis type I (162200) carry a heterozygous deletion of approximately 1.4 Mb involving the NF1 gene and contiguous genes lying in its flanking regions (Riva et al., 2000; Jenne et al., 2001), which is caused by nonallelic homologous recombination of NF1 repeats A and C (Dorschner et al., 2000). The 'NF1 microdeletion syndrome' is often characterized by a more severe phenotype than that observed in the majority of NF1 patients. In particular, patients with NF1 microdeletion often show variable facial dysmorphism, mental retardation, developmental delay, an excessive number of early-onset neurofibromas (Venturin et al., 2004), and an increased risk for malignant peripheral nerve sheath tumors (De Raedt et al., 2003).
An exageration of the normal arched form of the acetabular roof such that it takes on a steep appearance. [HPO:probinson]
This form of hyperaldosteronism is characterized by hypertension secondary to massive adrenal mineralocorticoid production. Like patients with glucocorticoid-remediable aldosteronism (GRA, or FH I; 103900), patients with FH III present with childhood hypertension, elevated aldosteronism levels, and high levels of the hybrid steroids 18-oxocortisol and 18-hydroxycortisol. However, hypertension and aldosteronism in FH III are not reversed by administration of exogenous glucocorticoids and patients require adrenalectomy to control hypertension (Geller et al., 2008). Reviews Mulatero et al. (2013) reviewed the role of KCNJ5 in adrenal pathophysiology and provided an overview of the clinical and biochemical phenotypes resulting from KCNJ5 mutations in patients with sporadic and familial primary aldosteronism. The authors stated that the prevalence of FH III appeared to be 7% of patients with familial aldosteronism and 0.3% of all cases of primary hyperaldosteronism. In addition, they noted that the total prevalence of reported KCNJ5 mutations in aldosterone-producing adrenal adenomas (APAs) was 40%.
Beaulieu-Boycott-Innes syndrome (BBIS) is an autosomal recessive neurodevelopmental disorder characterized by delayed development, moderate to severe intellectual disability, and dysmorphic facial features. Other developmental anomalies, such as cardiac and renal defects, cryptorchidism in males, submucous cleft palate, and corpus callosum dysgenesis, may also be present (summary by Beaulieu et al., 2013 and Amos et al., 2017).
Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and great toes, short stature, and moderate to severe intellectual disability. The characteristic craniofacial features are downslanted palpebral fissures, low-hanging columella, high palate, grimacing smile, and talon cusps. Prenatal growth is often normal; however, height, weight, and head circumference percentiles rapidly drop in the first few months of life. Obesity may occur in childhood or adolescence. IQ scores range from 25 to 79; average IQ is between 36 and 51. Other variable findings are coloboma, cataract, congenital heart defects, renal abnormalities, and cryptorchidism.
A syndromic limb malformation characterised by congenital onychodystrophy/anonychia, brachydactyly of the fifth finger, digitalisation of the thumbs, with absence or hypoplasia of the distal phalanges of the hands and feet in association with juvenile hypertrophy of the breast with gigantomastia in peripubertal females.
Carriers of the balanced constitutional translocation t(8;22)(q24.13;q11.2) are phenotypically normal but are at risk of having progeny with supernumerary der(22)t(8;22) syndrome as a result of malsegregation of the der(22). Although the supernumerary der(22)t(8;22) phenotype is variable between individuals, it tends to include ear and extremity abnormalities in addition to mild mental retardation (summary by Sheridan et al., 2010).
Klippel-Feil syndrome is a congenital anomaly characterized by a defect in the formation or segmentation of the cervical vertebrae, resulting in a fused appearance. The clinical triad consists of short neck, low posterior hairline, and limited neck movement, although less than 50% of patients demonstrate all 3 clinical features (Tracy et al., 2004). For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100).
Autosomal dominant hereditary sensory neuropathy type 1D is characterized by adult onset of a distal axonal sensory neuropathy affecting all modalities, often associated with distal ulceration and amputation as well as hyporeflexia, although some patients may show features suggesting upper neuron involvement (summary by Guelly et al., 2011). For a discussion of genetic heterogeneity of HSAN, see HSAN1A (162400). Spastic paraplegia-3A (SPG3A; 182600) is an allelic disorder with a different phenotype.
Thiamine metabolism dysfunction syndrome-4 is an autosomal recessive metabolic disorder characterized by childhood onset of episodic encephalopathy, often associated with a febrile illness, and causing transient neurologic dysfunction. Most patients recover fully, but some may have mild residual weakness. Affected individuals also develop a slowly progressive axonal polyneuropathy beginning in childhood. Brain imaging during the acute episodes shows lesions consistent with bilateral striatal degeneration or necrosis (summary by Spiegel et al., 2009). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270).
The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid. Total colonic aganglionosis and total intestinal HSCR also occur (Amiel et al., 2008). Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance (Amiel et al., 2008). For a discussion of genetic heterogeneity of susceptibility to Hirschsprung disease, see 142623.
Early infantile epileptic encephalopathy-11 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities (Ogiwara et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Autosomal recessive limb-girdle muscular dystrophy-17 is characterized by early childhood onset of proximal muscle weakness and atrophy without skin involvement. One family has shown rapid progression of the disorder in adolescence (summary by Gundesli et al., 2010). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
Autosomal recessive spinocerebellar ataxia-10 is an autosomal recessive neurodegenerative disorder with onset in the teenage or young adult years of gait and limb ataxia, dysarthria, and nystagmus associated with marked cerebellar atrophy on brain imaging (summary by Vermeer et al., 2010). Some patients have low levels of coenzyme Q10 (CoQ10) in muscle and may show some clinical improvement with CoQ10 treatment (Balreira et al., 2014).
Hemizygous 1.2-Mb deletion of the distal region of chromosome 7q11.23 is associated with increased risk for epilepsy, learning difficulties, intellectual disabilities, and/or neurobehavioral abnormalities (Ramocki et al., 2010).
HDBSCC is an autosomal recessive disorder with a distinctive phenotype comprising hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Affected individuals have a catastrophic neurologic clinical course resulting in death in infancy (summary by Akawi et al., 2013).
Acne inversa is a chronic inflammatory disease of the hair follicles whose characteristic features include draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. Familial acne inversa is genetically heterogeneous (summary by Wang et al., 2010). Some patients with PSENEN-associated acne inversa also exhibit reticulate hyperpigmentation consistent with Dowling-Degos disease (DDD; see 179850) (Zhou et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of acne inversa, see 142690.
Acne inversa is a chronic inflammatory disease of the hair follicles whose characteristic features include draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. Familial acne inversa is genetically heterogeneous (summary by Wang et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of familial acne inversa, see 142690.
P450scc deficiency is a rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are grossly elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure (summary by Kim et al., 2008). Although hormonal and phenotypic features can resemble those of congenital lipoid adrenal hyperplasia (lipoid CAH; 201710), no patient with P450scc deficiency has been described with the massive adrenal enlargement typical of lipoid CAH (summary by Sahakitrungruang et al., 2011).
Age-related macular degeneration (ARMD) is a common complex disorder that affects the central region of the retina (macula) and is the leading cause of legal blindness in white Americans over age 65. Contributions of environmental factors and genetic susceptibility have been identified. The strongest nongenetic risk factor for ARMD is cigarette smoking. For a general phenotypic description and a discussion of genetic heterogeneity of ARMD, see 603075.
Patients with deficiency of C8 suffer from recurrent neisserial infections, predominantly with meningococcus infection of rare serotypes. Most such patients are discovered among those having their first episode of meningitis at ages older than 10 years (Ross and Densen, 1984). Two types of inherited C8 deficiency have been reported in man: type I (613790), in which only C8 alpha (C8A, 120950) and C8 gamma (C8G; 120930) are deficient, and type II, in which only C8 beta is deficient (Marcus et al., 1982; Tedesco et al., 1983). The 2 types are clinically indistinguishable (Ross and Densen, 1984).
Patients with deficiency of C8 suffer from recurrent neisserial infections, predominantly with meningococcus infection of rare serotypes. Most such patients are discovered among those having their first episode of meningitis at ages older than 10 years (Ross and Densen, 1984). Two kinds of inherited C8 deficiency have been reported in man: type I, in which only C8 alpha and C8 gamma are deficient, and type II (613789), in which only C8 beta (C8B; 120960) is deficient (Marcus et al., 1982; Tedesco et al., 1983). The 2 types are clinically indistinguishable (Ross and Densen, 1984).
A reduced level of the complement component C8 in circulation.
Recurrent infections by bacteria of the genus Neisseria, including N. meningitidis (one of the most common causes of bacterial meningitis).
MASP2 deficiency, classically defined as MASP2 protein level of less than 100 ng/ml, occurs in about 4% of Caucasians and up to 18% of some African populations. Some MASP2-deficient individuals have increased risk of infection or autoimmune disease, but most are asymptomatic. MASP2 plays a role in activation of the lectin pathway of the complement system; deficiency may thus lead to defects in the complement system (summary by Thiel et al., 2007 and Sokolowska et al., 2015). For a discussion of genetic heterogeneity of lectin complement activation pathway defects, see LCAPD1 (614372).
IMD31B results from autosomal recessive (AR) STAT1 deficiency. STAT1 is crucial for cellular responses to IFNA (147660)/IFNB (147640) (type I interferon) and IFNG (147570) (type III interferon). AR STAT1 deficiency affects both the IFNA/IFNB and the IFNG pathways, resulting in susceptibility to mycobacteria, Salmonella, and viruses, with a severe disease course and often fatal outcome (review by Al-Muhsen and Casanova, 2008).
An abnormality of the combined rod-and-code response on electroretinogram.
PCH2D is an autosomal recessive disorder characterized by progressive microcephaly, postnatal onset of progressive atrophy of the cerebrum and cerebellum, profound mental retardation, spasticity, and variable seizures (summary by Ben-Zeev et al., 2003). For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (277470).
MDDGC9 is an autosomal recessive muscular dystrophy showing onset in early childhood. It is part of a group of similar disorders resulting from defective glycosylation of DAG1, collectively known as 'dystroglycanopathies' (summary by Hara et al., 2011). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
Seckel syndrome is an autosomal recessive disorder characterized by proportionate short stature, severe microcephaly, mental retardation, and a typical 'bird-head' facial appearance (summary by Kalay et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of Seckel syndrome, see 210600.
Generalized epilepsy with febrile seizures-plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. Seizure phenotypes include classic infantile febrile seizures, febrile seizures persisting beyond age 6 years or accompanied by afebrile generalized tonic-clonic seizures (GTCS), generalized or localization-related epilepsy, and more rarely, severe seizures with encephalopathy (summary by Poduri et al., 2009). For a discussion of genetic heterogeneity of GEFS+, see 604233.
CSNB1D is an autosomal recessive form of congenital stationary night blindness that is characterized by a Riggs type of electroretinogram (proportionally reduced a- and b-waves). Patients with Riggs-type CSNB have visual acuity within the normal range and no symptoms of myopia and/or nystagmus (summary by Riazuddin et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500).
Dihydrofolate reductase deficiency is an autosomal recessive metabolic disorder characterized by the hematologic findings of megaloblastic anemia and variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy (Banka et al., 2011) to childhood absence epilepsy with learning difficulties to lack of symptoms (Cario et al., 2011). Treatment with folinic acid can ameliorate some of the symptoms.
Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis, whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (summary by Gu et al., 1997). Mutation in TULP1 can also cause a form of autosomal recessive retinitis pigmentosa (RP14; 600132). For a general phenotypic description and a discussion of the genetic heterogeneity of Leber congenital amaurosis, see LCA1 (204000); for retinitis pigmentosa, see 268000.
HUPRA syndrome is a severe autosomal recessive multisystem disorder characterized by onset in infancy of progressive renal failure leading to electrolyte imbalances, metabolic alkalosis, pulmonary hypertension, hypotonia, and delayed development. Affected individuals are born prematurely (summary by Belostotsky et al., 2011).
Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type X is an autosomal recessive form characterized by multiple bone deformities and fractures, generalized osteopenia, dentinogenesis imperfecta, and blue sclera (Christiansen et al., 2010).
Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type XI is an autosomal recessive form of OI (summary by Alanay et al., 2010).
Multiple types of congenital heart defects are associated with mutation in the GDF1 gene, including tetralogy of fallot (TOF), transposition of the great arteries (TGA), double-outlet right ventricle (DORV), total anomalous pulmonary venous return (TAPVR), pulmonary stenosis or atresia, atrioventricular canal, ventricular septal defect (VSD), and hypoplastic left or right ventricle (Jin et al., 2017). For a discussion of genetic heterogeneity of multiple types of congenital heart defects, see 306955.
Individuals with ficolin-3 deficiency have highly variable manifestations and a variable age of symptom onset. Some patients may show increased susceptibility to infection in the perinatal or neonatal period, whereas others may show autoimmune features as adults. Ficolin-3, also known as H-ficolin, can activate the lectin pathway of the complement system; deficiency may thus lead to defects in the complement system (summary by Munthe-Fog et al., 2009 and Michalski et al., 2015). For a discussion of genetic heterogeneity of lectin complement activation pathway defects, see LCAPD1 (614372).
Retinitis pigmentosa (RP) describes a group of disorders with progressive degeneration of rod and cone photoreceptors in a rod-cone pattern of dysfunction. RP has a prevalence of 1 in 3,500, and is genetically and phenotypically heterogeneous (summary by Mackay et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Familial partial lipodystrophy type 4 is an autosomal dominant metabolic disorder characterized by childhood or young adult onset of loss of subcutaneous adipose tissue primarily affecting the lower limbs, insulin-resistant diabetes mellitus, hypertriglyceridemia, and hypertension (summary by Gandotra et al., 2011).
The chromosome 13q14 deletion syndrome is characterized by retinoblastoma (180200), variable degrees of mental impairment, and characteristic facial features, including high forehead, prominent philtrum, and anteverted earlobes (summary by Caselli et al., 2007).
OBHD is a neurodevelopmental disorder characterized by global developmental delay and hyperphagia resulting in obesity. Some patients may develop seizures (summary by Hamdan et al., 2017).
Spinocerebellar ataxia-32 (SCA32) is an autosomal dominant neurologic disorder characterized by ataxia, variable mental impairment, and azoospermia in males (summary by Jiang et al., 2010). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Acquired partial lipodystrophy (APLD) is characterized clinically by the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the 'cephalocaudal' sequence, sparing the lower extremities. A large group of patients (83%) with acquired partial lipodystrophy have low serum levels of complement component C3 due to the presence of C3 nephritic factor, an IgG antibody that causes continuous activation of the alternative complement pathway and consumption of serum C3. About 22% of patients with this acquired complement defect develop membranoproliferative glomerulonephritis. Some individuals may also show an increased risk of infection (Misra et al., 2004). Acquired partial lipodystrophy is not inherited in a classic mendelian pattern; it rather represents a phenotype with a complex etiology. Affected individuals may have genetic susceptibility factors that require the additional presence of environmental factors or acquired disorders to be expressed (summary by Hegele et al., 2006). Most cases are sporadic, family history is negative, and females are more often affected than males (ratio, 4:1) (summary by Misra et al., 2004). See 608709 for a subtype of APLD not associated with low complement C3 or renal disease.
Sleepwalking (SW) is a disorder in which a series of complex behaviors are initiated during slow-wave (non-REM) sleep and result in walking during sleep (American Academy of Sleep Medicine, 2005). It is a parasomnia, defined as a clinical disorder resulting in undesirable physical phenomena that occur predominantly during sleep. Parasomnias are not abnormalities of the processes responsible for sleep and wake states (summary by Hublin and Kaprio, 2003). Sleepwalking is more common in childhood (up to 26%), and usually resolves in adolescence; however, it can persist into adulthood (3%) (Hublin et al., 1997).
Primary localized cutaneous amyloidosis is characterized clinically by pruritus and skin scratching and histologically by the finding of deposits of amyloid staining on keratinous debris in the papillary dermis (summary by Tanaka et al., 2009). For a general description and a discussion of genetic heterogeneity of PLCA, see 105250.
Spermatogenic failure-9 is associated with globozoospermia, a rare phenotype of primary male infertility characterized by the production of a majority of round-headed spermatozoa without an acrosome (summary by Harbuz et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
GRIN2B-related neurodevelopmental disorder is characterized by mild to profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Muscle tone abnormalities (spasticity and/or hypotonia, occasionally associated with feeding difficulties), as well as epilepsy and autism spectrum disorder (ASD) / behavioral issues, are common. Other infantile- or childhood-onset findings include microcephaly; dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. Brain MRI reveals a malformation of cortical development in a minority of affected individuals. To date, fewer than 100 individuals with GRIN2B-related neurodevelopmental disorder have been reported.
Malignant melanoma is a neoplasm of pigment-producing cells called melanocytes that occurs most often in the skin, but may also occur in the eyes, ears, gastrointestinal tract, leptomeninges, and oral and genital mucous membranes (summary by Habif, 2010). For a discussion of genetic heterogeneity of cutaneous malignant melanoma, see 155600.
Neonatal cyanosis is characterized by symptoms in the fetus and neonate that gradually abate by 5 to 6 months of age. The disorder is caused by a defect in the fetal hemoglobin chain, which causes reduced affinity for oxygen due to steric inhibition of oxygen binding and/or due to increased oxidation of the fetal hemoglobin molecule to methemoglobin (Hb FM), which has decreased oxygen-binding capacity. Some patients develop anemia resulting from increased destruction of red cells containing abnormal or unstable hemoglobin. The cyanosis resolves spontaneously by 5 to 6 months of age or earlier, as the adult beta-globin chain (HBB; 141900) is produced and replaces the fetal gamma-globin chain (summary by Crowley et al., 2011).
Hypotrichosis simplex can affect all body hair (generalized; see 605389) or be limited to the scalp. Usually patients with the scalp-limited form of hypotrichosis present with normal hair at birth; they experience a progressive, gradual loss of scalp hair beginning at the middle of the first decade and leading to almost complete loss of scalp hair by the third decade. A few sparse, fine, short hairs remain in some individuals. Body hair, beard, eyebrows, axillary hair, teeth, and nails develop normally. Light and electron microscopy of hairs from patients with early hypotrichosis simplex revealed no structural changes, whereas hairs from patients with advanced hypotrichosis showed focal areas of defective cuticular structure. Men and women are equally affected (summary by Betz et al., 2000). For a discussion of genetic heterogeneity of nonsyndromic hypotrichosis, see HYPT1 (605389).
Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type XII is an autosomal recessive form characterized by recurrent fractures, mild bone deformations, generalized osteoporosis, delayed teeth eruption, progressive hearing loss, no dentinogenesis imperfecta, and white sclerae (summary by Lapunzina et al., 2010).
Lissencephaly-4 is an autosomal recessive neurodevelopmental disorder characterized by lissencephaly, severe brain atrophy, extreme microcephaly (head circumference of more than 10 standard deviations (SD) below the mean), and profound mental retardation. It has also been referred to as 'microlissencephaly' (summary by Bakircioglu et al., 2011 and Alkuraya et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Protein Z serves as a cofactor for the downregulation of coagulation by forming a complex with the protein Z-dependent protease inhibitor (ZPI; 605271). Evidence also suggests that protein Z may promote the assembly of thrombin with phospholipid surfaces, thus enhancing coagulation. There is a wide variation of protein Z levels in human plasma, and studies have reported conflicting results of the clinical consequences of protein Z deficiency in humans. Most studies have reported an association between decreased protein Z levels and thrombosis, including stroke, venous thrombosis, and obstetric complications, although early reports suggested an association between protein Z deficiency and bleeding tendency (Kemkes-Matthes and Matthes, 1995). Overall, a role for protein Z in the pathogenesis of hemostatic disorders in humans is controversial and remains unclear (review by Broze, 2001 and Vasse, 2008). Protein Z deficiency has been shown to exacerbate the thrombotic phenotype in patients with thrombophilia due to factor V Leiden (see 188055).
Hepatic lipase deficiency is a disorder that affects the body's ability to break down fats (lipids). People with this disorder have increased amounts of certain fats, known as triglycerides and cholesterol, in the blood. These individuals also have increased amounts of molecules known as high-density lipoproteins (HDLs) and decreased amounts of molecules called low-density lipoproteins (LDL). These molecules transport triglycerides and cholesterol throughout the body. In people with hepatic lipase deficiency, the LDL molecules are often abnormally large.Normally, high levels of HDL (known as ""good cholesterol"") and low levels of LDL (known as ""bad cholesterol"") are protective against an accumulation of fatty deposits on the artery walls (atherosclerosis) and heart disease. However, some individuals with hepatic lipase deficiency, who have this imbalance of HDL and LDL, develop atherosclerosis and heart disease in mid-adulthood, while others do not. It is unknown whether people with hepatic lipase deficiency have a greater risk of developing atherosclerosis or heart disease than individuals in the general population. Similarly, it is unclear how increased blood triglycerides and cholesterol levels affect the risk of atherosclerosis and heart disease in people with hepatic lipase deficiency.
Palmoplantar keratoderma and congenital alopecia-1 (PPKCA1) is a rare autosomal dominant disorder characterized by severe hyperkeratosis and congenital alopecia. Nail changes occur in some patients (summary by Castori et al., 2010). Also see PPKCA2 (212360), an autosomal recessive disorder characterized by congenital alopecia and progressive hyperkeratosis resulting in sclerodactyly, severe contractures and tapering of the digits, and pseudoainhum formation.
SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterized in the majority of affected newborns by hypotonia, muscle atrophy, feeding difficulties, and lactic acidosis. Affected infants commonly manifest developmental delay / cognitive impairment, growth retardation / failure to thrive, hepatopathy, sensorineural hearing impairment, dystonia, and hypertonia. Notable findings in some affected individuals include hypertrophic cardiomyopathy, epilepsy, myoclonus, microcephaly, sleep disturbance, rhabdomyolysis, contractures, hypothermia, and/or hypoglycemia. Life span is shortened, with median survival of 20 months.
The two forms of deoxyguanosine kinase (DGUOK) deficiency are a neonatal multisystem disorder and an isolated hepatic disorder that presents later in infancy or childhood. The majority of affected individuals have the multisystem illness with hepatic disease (jaundice, cholestasis, hepatomegaly, and elevated transaminases) and neurologic manifestations (hypotonia, nystagmus, and psychomotor retardation) evident within weeks of birth. Those with isolated liver disease may also have renal involvement and some later develop mild hypotonia. Progressive hepatic disease is the most common cause of death in both forms.
An autosomal recessive muscular dystrophy caused by mutations in the POMGNT1 gene. It is associated with characteristic brain and eye malformations, profound mental retardation, and death usually in the first years of life.
The presence of an abnormal curvature of the cervical vertebral column.
Nephrotic syndrome, a malfunction of the glomerular filter, leads to proteinuria, edema, and, in steroid-resistant nephrotic syndrome, end-stage renal disease (ESRD). Renal histopathology in NPHS4 due to WT1 mutations most often shows diffuse mesangial sclerosis (DMS), but can also show focal segmental glomerulosclerosis (FSGS). Both of these terms refer to pathologic findings and may be associated with the same clinical phenotype, namely nephrotic syndrome (review by Schumacher et al., 1998). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). In sclerocornea there is congenital, nonprogressive corneal opacification that may be peripheral, sectoral, or central in location. Visual prognosis is related to the central corneal involvement. The cornea has a flat curvature. The majority of cases are bilateral (summary by Smith and Traboulsi, 2012). Isolated sclerocornea is caused by displacement of the limbal arcades and may be associated with cornea plana; in this condition, the anterior chamber is visible and the eye is not microphthalmic. In complex sclerocornea, however, corneal opacification is associated with microphthalmia, cataract, and/or infantile glaucoma. The central cornea is usually relatively clear, but the thickness is normal or increased, never reduced (summary by Nischal, 2007).
This progressive neurodegenerative disorder is characterized by early childhood onset of spastic ataxia with mental retardation, cerebellar signs, and variable optic atrophy (Hogan and Bauman, 1977).
This multisystem disorder is characterized by moyamoya disease, short stature, hypergonadotropic hypogonadism, and facial dysmorphism. Other variable features include dilated cardiomyopathy, premature graying of the hair, and early-onset cataracts. Moyamoya disease is a progressive cerebrovascular disorder characterized by stenosis or occlusion of the internal carotid arteries and the main branches, leading to the development of small collateral vessels (moyamoya vessels) at the base of the brain. Affected individuals can develop acute neurologic events due to stroke-like episodes (summary by Miskinyte et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of moyamoya disease, see MYMY1 (252350).
Infantile mitochondrial myopathy due to reversible COX deficiency is a rare mitochondrial disorder characterized by onset in infancy of severe hypotonia and generalized muscle weakness associated with lactic acidosis, but is distinguished from other mitochondrial disorders in that affected individuals recover spontaneously after 1 year of age (summary by Mimaki et al., 2010). See also transient infantile liver failure (LFIT; 613070), which is a similar disorder.
Progressive bending or abnormal curvature of the forearm skeleton.
D-2-hydroxyglutaric aciduria is a neurometabolic disorder first described by Chalmers et al. (1980). Clinical symptoms include developmental delay, epilepsy, hypotonia, and dysmorphic features. Mild and severe phenotypes were characterized (van der Knaap et al., 1999). The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and, often, cardiomyopathy. The mild phenotype has a more variable clinical presentation. Genetic Heterogeneity of D-2-Hydroxyglutaric Aciduria D-2-hydroxyglutaric aciduria-2 (D2HGA2; 613657) is caused by heterozygous mutation in the mitochondrial isocitrate dehydrogenase-2 gene (IDH2; 147650) on chromosome 15q26.
Agammaglobulinemia is a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. The most common form of agammaglobulinemia is X-linked agammaglobulinemia (AGMX1, XLA; 300755), also known as Bruton disease, which is caused by mutation in the BTK gene (300300). AGMX1 accounts for anywhere from 85 to 95% of males who have the characteristic findings (Lopez Granados et al., 2002; Ferrari et al., 2007). Autosomal recessive inheritance of agammaglobulinemia, which has a similar phenotype to that of the X-linked form, has been observed in a small number of families, and accounts for up to 15% of patients with agammaglobulinemia (Ferrari et al., 2007). Conley (1999) gave a comprehensive review of autosomal recessive agammaglobulinemia. Genetic Heterogeneity of Autosomal Agammaglobulinemia Autosomal agammaglobulinemia is a genetically heterogeneous disorder: see also AGM2 (613500), caused by mutation in the IGLL1 gene (146770); AGM3 (613501), caused by mutation in the CD79A gene (112205); AGM4 (613502), caused by mutation in the BLNK gene (604515); AGM5 (613506), caused by disruption of the LRRC8 gene (608360); AGM6 (612692), caused by mutation in the CD79B gene (147245); AGM7 (615214), caused by mutation in the PIK3R1 gene (171833); and AGM8 (616941), caused by mutation in the TCF3 gene (147141).
Abnormality of the anterior chamber, which is the space in the eye that is behind the cornea and in front of the iris.
The PR (or PQ) interval is the time required for an electrical impulse to travel from the atrial myocardium adjacent to the sinus node through the atrioventricular node (AVN) to the Purkinje fibers. Delayed conduction results in prolongation of the PR interval and subsequent risk of atrial fibrillation (summary by Holm et al., 2010). The PR interval has a substantial heritable component, with heritability estimates ranging between 30 and 50%. The PR interval is considered an intermediate phenotype for atrial fibrillation, as alterations in atrial action potential duration and in atrioventricular conduction influence both PR interval and atrial fibrillation risk (summary by Pfeufer et al., 2010).
A pneumococcal conjugate vaccine containing 13 different strains of the bacterium Streptococcus pneumoniae, used in children and studied in immunocompromised patients for the prevention of pneumococcal disease. The pneumococcal 13-valent conjugate vaccine contains capsular antigen polysaccharides derived from the S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F that are individually conjugated to a nontoxic diphtheria cross-reactive material (CRM) carrier protein (CRM197). Upon vaccination, pneumococcal 13-valent conjugate vaccine induces active immunization against 13 different serotypes of S. pneumoniae and protects against pneumococcal disease.
A device that has exceeded the period of time/date recommended by the manufacturer for storing the device without a degradation in quality.
A device that cannot calibrate (establish the relationship between a measuring device and the units of measure) to ensure accurate readings.
Bornholm eye disease consists of X-linked high myopia, amblyopia, and deuteranopia. Associated signs include optic nerve hypoplasia, reduced electroretinographic (ERG) flicker, and nonspecific retinal pigment abnormalities (Schwartz et al., 1990).
A disorder characterized by an unpleasant sensation of irregular and/or forceful beating of the heart.
Mixed; being composed of a combination of normal and tumor cells.
An abnormality of coagulation associated with an increased risk of thrombosis.
The catalyzed removal of phosphate groups from biological molecules, by phosphatases.
An acute or subacute reversible condition characterized by headaches, mental status changes, visual disturbances, and seizures associated with imaging findings of posterior leukoencephalopathy. It has been observed in association with hypertensive encephalopathy, eclampsia, and immunosuppressive and cytotoxic drug treatment.
A transitional cell carcinoma which has spread from the original site of growth to another anatomic site.
Constipation that results from, or follows, treatment with an opioid or opioid-containing medication.
A form of interstitial lung disease characterized by increased numbers of pulmonary neuroendocrine cells, typically presenting in the first year of life with persistent tachypnea, retractions, crackles and hypoxemia that has a highly specific chest CT pattern that includes ground-glass opacities and air-trapping.
Hemoglobin H disease is a subtype of alpha-thalassemia (see 604131) in which patients have compound heterozygosity for alpha(+)-thalassemia, caused by deletion of one alpha-globin gene, and for alpha(0)-thalassemia, caused by deletion in cis of 2 alpha-globin genes (summary by Lal et al., 2011). When 3 alpha-globin genes become inactive because of deletions with or without concomitant nondeletional mutations, the affected individual has only 1 functional alpha-globin gene. These people usually have moderate anemia and marked microcytosis and hypochromia. In affected adults, there is an excess of beta-globin chains within erythrocytes that will form beta-4 tetramers, also known as hemoglobin H (summary by Chui et al., 2003). Hb H disease is usually caused by the combination of alpha(0)-thalassemia with deletional alpha(+)-thalassemia, a combination referred to as 'deletional' Hb H disease. In a smaller proportion of patients, Hb H disease is caused by an alpha(0)-thalassemia plus an alpha(+)-thalassemia point mutation or small insertion/deletion. Such a situation is labeled 'nondeletional' Hb H disease. Patients with nondeletional Hb H disease are usually more anemic, more symptomatic, more prone to have significant hepatosplenomegaly, and more likely to require transfusions (summary by Lal et al., 2011). While most thalassemia-related hydrops fetalis is caused by the lack of all alpha-globin genes, there are reports of fetuses with Hb H disease that developed the hydrops fetalis syndrome; see 236750.
Vitreomacular traction is characterized by anomalous posterior vitreous detachment accompanied by anatomic distortion of the fovea, which may include pseudocysts, macular schisis, cystoid macular edema, and subretinal fluid. Vitreomacular traction can be subclassified by the diameter of vitreous attachment to the macular surface as measured by OCT, with attachment of 1500 micrometers or less defined as focal and attachment of more than 1500 micrometers as broad.
Profound mental retardation is defined as an intelligence quotient (IQ) below 20. [HPO:probinson]
A class of drugs that stimulate sodium influx through cell membrane channels.
Loss of blood from the circulation, either internally or externally.
For internal or topical application, Anti-infective Preparations contain natural or synthetic antibiotic agents that act therapeutically or prophylactically against infectious viral, bacterial, protozoal, or other agents by inhibiting their growth, replication, and survival. Usually, antiinfective preparations are formulated sterile. (NCI04)
An animal source of thyroid used in hormonal replacement therapy. Thyroid extract or desiccated thyroid contains both levothyroxine (thyroxine or T4) and liothyronine (triiodothyronine or T3). Levothyroxine is deiodinated in the peripheral tissues to produce increased levels of its active form, liothyronine (T3). Thyroid hormones play an important role in the regulation of cellular respiration, thermogenesis, cellular growth and differentiation as well as regulating the metabolism of proteins, carbohydrates, and lipids.
A disorder characterized by a blood pressure that is below the normal expected for an individual in a given environment.
A WHO grade III meningioma characterized by the predominance of a perivascular pseudopapillary pattern.
Hemorrhage from the vagina that may range from light spotting to heavy flow during pregnancy.
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections. [HPO:probinson]
A venous pouch within the left ventricular wall, with a neck opening into the coronary sinus.
A developmental defect characterized by the lack of aortic valve cusps (leaflets). There may be remnants of the aortic valve in form of a nonobstructive fibrous ridge or rudimentary leaflets or sinuses of Valsalva.
Any structural abnormality of the pulmonary valve.
Both lungs have three lobes. Normally, the left lung has two lobes, whereas the right lung has three lobes.
Common atrium without defining morphologic features.
A primary or metastatic malignant neoplasm that affects the lung parenchyma, bronchial tree, or trachea. Representative examples include lung carcinoma, carcinoid tumor, lung lymphoma, lung sarcoma, and tracheal carcinoma.
Presence of either fever, hypotension, or oliguria in a patient who meets the following three criteria: blood was not cultured or no microorganism was isolated; there was no apparent infection at another site; and appropriate antimicrobial therapy for sepsis was initiated.
A compression of ILIAC VEIN that results in a decreased flow in the vein and in the left LOWER EXTREMITY due to a vascular malformation. It may result in left leg EDEMA, pain, iliofemoral DEEP VENOUS THROMBOSIS and POSTTHROMBOTIC SYNDROME. Compression of the left common ILIAC VEIN by the right common ILIAC ARTERY against the underlying fifth LUMBAR VERTEBRA is the typical underlying malformation.
A double outlet right ventricle with a subaortic ventritricular septal defect (a hotel between the two bottom chambers (ventricles) of the heart), that extends anterosuperiorly and arere closely related to the pulmonary artery as well, are considered to be doubly committed. There is associated pulmonary stenosis, the abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
A ventricular septal defect that lies beneath the semilunar valve(s) in the conal or outlet septum.
A difficult or dangerous health situation that needs urgent attention.
A response indicating that an individual has not experienced any fatigue.
Thyroid hormone deficiency present at birth and caused by iodine deficiency.
A carbamate and thiazole derivative that functions as a CYTOCHROME P450 CYP3A INHIBITOR to enhance the concentration of ANTI-HIV AGENTS, with which it is used in combination, for the treatment of HIV INFECTIONS.
An orally bioavailable focal adhesion kinase (FAK) inhibitor with potential antineoplastic activity. Upon administration, VS-4718 inhibits FAK, blocks fibronectin-stimulated FAK autophosphorylation of Tyr397, and may prevent the integrin-mediated activation of several downstream signal transduction pathways, including ERK, JNK/MAPK and PI3K/Akt. This results in the reduction of the number of cancer stem cells (CSCs) and inhibits tumor cell migration, proliferation and survival. The cytoplasmic tyrosine kinase FAK is a signal transducer for integrins and is constitutively activated in various tumor cell types; it is involved in tumor cell invasion, migration and proliferation and plays a key role in the development, function and survival of CSCs.
An N-acetylated, glycol-split form of heparin that is devoid of anticoagulant activity and is an inhibitor of heparanase with antineoplastic and antiangiogenic activities. Upon subcutaneous administration, heparin derivative SST0001 inhibits the activity of heparanase. This prevents the heparanase-mediated cleavage of heparan sulfate (HS) proteoglycans on cell surfaces and within the extracellular matrix. In addition, this agent prevents the heparanase-induced production of a number of angiogenic growth factors, including matrix metalloproteinase-9, hepatocyte growth factor and vascular endothelial growth factor. Altogether, this leads to an inhibition of both tumor cell growth and angiogenesis. Heparanase, an enzyme that is responsible for the proteolytic cleavage of proteoglycans, is upregulated in a variety of tumor cell types and promotes tumor cell growth; it plays a key role in tumor cell invasion, metastasis and angiogenesis.
Dull or sharp aching pain caused by stimulated NOCICEPTORS due to tissue injury, inflammation or diseases. It can be divided into somatic or tissue pain and VISCERAL PAIN.
Compression of the left renal vein between the superior mesenteric artery and the abdominal aorta causing an increase in the pressure gradient between the left renal vein and the inferior vena cava. The thin septae between the veins and the collecting system in the renal fornices rupture, with resultant left sided haematuria. Most symptomatic cases present in the third or fourth decade of life, with women being more commonly affected than men. Three types of renal nutcracker syndrome have been defined: anterior nutcracker syndrome, posterior nutcracker syndrome and combined nutcracker syndrome.
Necrotic jaws or other maxillofacial skeleton necrosis associated with bisphosphonate use (see BISPHOSPHONATES). Injury, dental procedures, and trauma can trigger the necrotic process.
Loss of vascular ELASTICITY due to factors such as AGING; and ARTERIOSCLEROSIS. Increased arterial stiffness is one of the RISK FACTORS for many CARDIOVASCULAR DISEASES.
The elastic properties of the aorta allow the aorta to store half of the cardiac ejected blood volume per beat, whereby aortic recoil during diastole pushes the remaining stored volume forward into the peripheral circulation, a phenomenon known as the Windkessel function. Aortic stiffness occurs as the elastic fibers within the arterial wall become disrupted due to mechanical stress (with age or due to other factors). Aortic stiffness refers to a reduction in the elasticity of the aorta, which is associated with an elevated pulse pressure, increased wave reflection, and often hypertension.
A condition in which the nerves register normal stimuli (lack of tissue injury) as pain, resulting in feelings of intense pain with even minor sensory input.
A reaction that severs one of the sugar-phosphate linkages of the phosphodiester backbone of RNA. It is catalyzed enzymatically, chemically, or by radiation. Cleavage may be exonucleolytic, or endonucleolytic.
Stroke caused by lacunar infarction or other small vessel diseases of the brain. It features hemiparesis (see PARESIS), hemisensory, or hemisensory motor loss.
Right atrial isomerism is characterized by bilateral triangular, morphologically right atrial, appendages, both joining the atrial chamber along a broad front with internal terminal crest.
In left atrial isomerism there is a bilateral small finger-shaped morphologically left atrial appendage joining the atrial chamber along a narrow front without an internal terminal crest.
Biological products that are imitations but not exact replicas of innovator biological products.
Phenomenon where increased BLOOD PRESSURE readings taken in non-clinical settings (e.g., HOME BLOOD PRESSURE MONITORING) do not replicate in clinical settings.
Ocular manifestations secondary to various NEOPLASMS in which antibodies to antigens of the primary tumor cross-react with ocular antigens. This autoimmune response often leads to visual loss and other ocular dysfunctions.
Infections with bacteria of the genus ALIIVIBRIO.
Pain-alleviating drugs characterized by rapid action time.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
CNS infections caused by neurotropic dematiaceous fungi that contain melanin in their cell walls. The infections often result in BRAIN ABSCESS; ENCEPHALITIS; and MENINGITIS in patients who are often immunocompetent. The common causative fungi include members Cladophialophora bantiana, Exophiala dermatitidis, Rhinocladiella mackenziei, and Ochroconis gallopavum. R. mackenziei infection is seen almost exclusively in patients from the MIDDLE EAST.
The shifting and or tilting of implanted artificial lens resulting in impaired vision.
Opportunistic fungal infection by a member of ALTERNARIA genus.
Impairment in mathematical abilities secondary to a damage to a specific region of the brain often caused by a stroke, tumor, or trauma.
A degradation process whereby incorrectly folded proteins are selectively transported out of the ENDOPLASMIC RETICULUM and into the CYTOSOL. The misfolded proteins are subsequently ubiquitinated and degraded by the PROTEASOME.
Malalignment of a bone in which its head and neck is rotated excessively forward or inward.
Attachment of a bone in which its head and neck is rotated excessively backward.
Natural compounds containing alternating carbonyl and methylene groups (beta-polyketones), bioenergenetically derived from repeated condensation of acetyl coenzyme A via malonyl coenzyme A, in a process similar to fatty acid synthesis.
Chemical agents that increase the permeability of CELL MEMBRANES to PROTONS.
DOSAGE FORMS of NICOTINE designed to deliver nicotine to the body as alternatives to using TOBACCO.
GRANULOCYTE morphologic changes similar to the cells in familial Pelger-Huet anomoly. Granulocytes have abnormal bilobular morphology with hypercondensation due to drug therapy or secondary to diseases such as MYELODYSPLASTIC SYNDROMES and ACUTE MYELOID LEUKEMIA.
A humanized immunoglobulin (Ig) G4 monoclonal antibody against CC chemokine receptor 5 (CCR5; CD195), with potential activity as a human immunodeficiency virus (HIV) entry blocker and potential protective activity against graft-versus-host disease (GvHD). Upon administration, PRO 140 targets and binds to CCR5 expressed on T-cells. This blocks HIV cell entry, which prevents HIV infection and/or reduces HIV viral load. In addition, blocking CCR5 by PRO 140 decreases CCR5-mediated signaling and the CCR5-induced migration of donor cells into tissues after an allogeneic hematopoietic cell transplantation (HCT). Blocking CCR5 may therefore prevent or reduce GvHD. CCR5, a co-receptor needed for HIV cell entry, plays a key role in immunomodulation. Expressed on monocytes, activated T-cells and dendritic cells (DCs), CCR5 can regulate chemotaxis. Lymphocyte trafficking via chemokine receptors, such as CCR5, and recruitment to target organs, plays a critical role in alloreactive responses.
A gastrointestinal stromal tumor that is characterized by large size (diameter greater than 10 cm for gastric localization and greater than 5 cm for intestinal localization) or more than 5 mitotic figures per 50 high power fields.
A phenylethylamine derivative that acts as a calcium antagonist showing hemodynamic effects in patients with acute myocardial infarction.
An IgG2 humanized monoclonal antibody against the pro-inflammatory cytokine interleukin 1 beta (IL-1b) with anti-inflammatory activity. Gevokizumab binds to IL-1b, thereby preventing IL-1b-mediated inflammatory responses. This antibody has a long half life and allows for once a month dosing intervals.
Deficiency of surfactant protein B. It presents with severe respiratory distress-like illness and responds poorly to exogenous administration of surfactant.
A synthetic, non-recombinant, pegylated, peptidic erythropoiesis stimulating agent. Synthetic peptide-based erythropoiesis stimulating agent binds to and activates the erythropoietin (EPO) receptor on erythroid progenitor cells, thereby inducing their proliferation and differentiation into mature erythrocytes.
An orally bioavailable inhibitor of RNA polymerase I (Pol I), with potential antineoplastic activity. Upon oral administration, CX-5461 selectively binds to and inhibits Pol I, prevents Pol I-mediated ribosomal RNA (rRNA) synthesis, induces apoptosis, and inhibits tumor cell growth. Pol I, the multiprotein complex that synthesizes rRNA, is upregulated in cancer cells and plays a key role in cell proliferation and survival. Hyperactivated rRNA transcription is associated with uncontrolled cancer cell proliferation.
A heterozygous deletion of chromosome 15q11.2 may increase the susceptibility to neuropsychiatric or neurodevelopmental problems, including delayed psychomotor development, speech delay, autism spectrum disorder, attention deficit-hyperactivity disorder, obsessive-compulsive disorder, and possibly seizures (summary by Doornbos et al., 2009 and Burnside et al., 2011). See also chromosome 15q11.2 duplication syndrome (608636).
A cancer vaccine consisting of a human epidermal growth factor receptor variant III (EGFRvIIi)-specific peptide conjugated to the non-specific immunomodulator keyhole limpet hemocyanin (KLH) with potential antineoplastic activity. Vaccination with rindopepimut may elicit a cytotoxic T-lymphocyte (CTL) immune response against tumor cells expressing EGFRvIII. EGFRvIII, a functional variant of EGFR that is not expressed in normal tissues, was originally discovered in glioblastoma multiforme (GBM) and has also been found in various other cancers such as breast, ovarian, metastatic prostate, colorectal, and head and neck cancers. EGFRvIII contains an 83 amino acid deletion in its extracellular domain and has been shown to transform NIH/3T3 mouse embryonic fibroblast cells in vitro.
An orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several RTKs, which are often overexpressed in a variety of cancer cell types, including hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL. This may result in an inhibition of both tumor growth and angiogenesis, and eventually lead to tumor regression.
An indole sulfonamide compound and inhibitor of BRAF KINASES that is used for the treatment of unresectable or metastatic MELANOMA.
Formation of a non-infectious THROMBUS, referred to as vegetation, on previously undamaged ENDOCARDIUM. It usually occurs as a complication of connective-tissue diseases and cancers because of the associated hypercoagulable state (see THROMBOPHILIA).
A chemically-modified tetracycline with potential antineoplastic activity. Incyclinide inhibits matrix metalloproteinases (MMPs), thereby inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. This agent also causes mitochondrial depolarization in tumor cells and induces both cellular apoptosis and tissue necrosis.
The score derived from universally embraced prostate cancer grading system developed by Dr. Donald F. Gleason in 1977. The system provides a reproducible description of the glandular architecture of prostate tissue to which a pathologist assigns a score depending primarily on the microscopic patterns of cancerous glands and cell morphology. The system correlates well with behavior at the extremes: Gleason 1+1 tumors are the most well differentiated, slowly growing and rarely spread; Gleason 4+5 tumors are the most poorly differentiated, often widely metastatic at the time of diagnosis. In the commoner intermediate grade tumors, however, behavior is extremely variable.
A costimulatory receptor that is specific for INDUCIBLE T-CELL CO-STIMULATOR LIGAND. The receptor is associated with a diverse array of immunologically-related effects including the increased synthesis of INTERLEUKIN 10 in REGULATORY T-LYMPHOCYTES and the induction of PERIPHERAL TOLERANCE.
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
A reduction in the amount of air entering the pulmonary alveoli.
A pathologic process consisting of the formation and discharge of pus.
A benign cartilaginous tumors of the lung.
An decreased concentration of magnesium the urine.
Overwhelming emotional damage caused by a distressful event or series of events.
A recently described mass-forming lesion that occurs in the pancreas, submandibular glands, lacrimal glands, lymph nodes, and hepatobiliary tract. It is characterized by the presence of marked tissue sclerosis and infiltration by numerous plasma cells. The plasma cells show immunohistochemical staining for IgG4 and the serum IgG4 levels are often increased.
Presence of air or gas within the spinal canal cavity (EPIDURAL SPACE; or SUBARACHNOID SPACE). It may result from traumatic injuries, emphysema, infection and other conditions. It can also develop as a complication of various SURGICAL PROCEDURES (e.g., MYELOGRAPHY).
Characterized by urinary retention associated with abnormal electromyographic activity in young women in the absence of overt neurologic disease. May also be associated with polycystic ovaries in some women.
A severe, sometimes life-threatening, form of erythema multiforme. It is considered to be a hypersensitivity skin reaction triggered by a variety of stimuli, including infections and medication. It is characterized by raised, edematous papules in the extremities; involvement of one or more mucous membranes; and epidermal detachment involving less than ten percent of the total body surface area.
Pulmonary edema that is not a result of cardiac dysfunction.
Fatty replacement and damage to the hepatocytes not related to alcohol use. It may lead to cirrhosis and liver failure.
A disorder that affects the muscle tissue of the heart. Representative examples include myocardial infarction, myocarditis, and cardiomyopathy.
An adult who has smoked 100 cigarettes in his or her lifetime and who currently smokes cigarettes. Includes daily smokers and non-daily smokers (also known as occasional smokers).
A peptide vaccine consisting of amino acids 12 through 20 of the viral oncoprotein human papillomavirus (HPV) 16 E7. Vaccination with HPV-16 E7 peptide may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for HPV-16 E7, resulting in decreased tumor growth. HPV-16 infection is tumorigenic and highly associated with cervical cancer. (NCI04)
Description:The information was recorded incorrectly or was recorded in the wrong record.
A genetically-engineered, chimeric mouse-human, anti-CD30 monoclonal antibody with potential antineoplastic activity. Brentuximab specifically binds to the receptor CD-30, a member of the tumor necrosis factor receptor super-family, which may be overexpressed on the surfaces of Hodgkin lymphoma cells and anaplastic-large cell lymphoma cells. After binding to CD30, this agent interferes with the G1 phase of the cell cycle, thereby inducing growth arrest and apoptosis in susceptible tumor cell populations.
The phosphate salt form of ruxolitinib, an orally bioavailable Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. Ruxolitinib specifically binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies.
Myotonic dystrophy type 1 (DM1) is a multisystem disorder that affects skeletal and smooth muscle as well as the eye, heart, endocrine system, and central nervous system. The clinical findings, which span a continuum from mild to severe, have been categorized into three somewhat overlapping phenotypes: mild, classic, and congenital. Mild DM1 is characterized by cataract and mild myotonia (sustained muscle contraction); life span is normal. Classic DM1 is characterized by muscle weakness and wasting, myotonia, cataract, and often cardiac conduction abnormalities; adults may become physically disabled and may have a shortened life span. Congenital DM1 is characterized by hypotonia and severe generalized weakness at birth, often with respiratory insufficiency and early death; intellectual disability is common.
depression in women occurring usually shortly after childbirth
An orally available inhibitor of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) replication complex, with potential activity against HCV. Although the exact mechanism of action of daclatasvir has yet to be fully determined, this agent, upon oral administration and after intracellular uptake, appears to bind to domain I of the NS5A protein. This inhibits the activity of the NS5A protein and results in the disruption of the viral RNA replication complex, blockage of viral HCV RNA production, and inhibition of viral replication. NS5A, a zinc-binding and proline-rich hydrophilic phosphoprotein, plays a crucial role in HCV RNA replication. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family.
An orally available valproic acid prodrug of gemcitabine, a broad-spectrum antimetabolite and deoxycytidine analogue with antineoplastic activity. Upon administration, gemcitabine prodrug LY2334737 is hydrolyzed by carboxylesterase 2 (CES2) and releases gemcitabine systemically over a period of time consistent with formation rate-limited kinetics. In turn, gemcitabine is converted into the active metabolites difluorodeoxycytidine diphosphate and triphosphate (dFdCDP and dFdCTP) by deoxycytidine kinase. dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA replication; dFdCTP is incorporated into DNA, resulting in premature termination of DNA replication and eventually the induction of apoptosis. Compared to gemcitabine, this prodrug is able to avoid hydrolysis in enterocytes and the portal circulation thus avoiding first pass metabolism and increasing systemic gemcitabine availability. In addition, the slow release of gemcitabine may enhance efficacy while lowering toxicity. CES2, a serine ester hydrolase, is expressed in certain tumors which may allow for increased conversion of gemcitabine at the tumor site thus increases cytotoxicity.
An orally bioavailable inhibitor of colony stimulating factor 1 receptor (CSF-1R; CSF1R), with potential antineoplastic activity. CSF1R inhibitor BLZ945 selectively binds to CSF1R expressed on tumor-associated macrophages (TAMs), blocks the activity of CSF1R, and inhibits CSF1R-mediated signal transduction pathways. This inhibits the activity and proliferation of TAMs, and reprograms the immunosuppressive nature of existing TAMs. Altogether, this reduces TAM-mediated immune suppression in the tumor microenvironment, re-activates the immune system, and improves anti-tumor cell responses mediated by T-cells. CSF1R, also known as macrophage colony-stimulating factor receptor (M-CSFR) and CD115 (cluster of differentiation 115), is a cell-surface receptor for its ligand, colony stimulating factor 1 (CSF1); this receptor is overexpressed by TAMs in the tumor microenvironment, and plays a major role in both immune suppression and the induction of tumor cell proliferation.
A 3-cyanoquinoline pan-ErbB tyrosine kinase inhibitor with potential antineoplastic activity. Pelitinib irreversibly binds covalently to epidermal growth factor receptors (EGFR) ErbB-1, -2 and -4, thereby inhibiting receptor phosphorylation and signal transduction and resulting in apoptosis and suppression of proliferation in tumor cells that overexpress these receptors.
An orally bioavailable HDM2 antagonist with potential antineoplastic activity.Serdemetan inhibits the binding of the HDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this HDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited, which may result in the restoration of p53 signaling and thus the p53-mediated induction of tumor cell apoptosis. HDM2 (human homolog of double minute 2), a zinc finger protein, is a negative regulator of the p53 pathway; often overexpressed in cancer cells, it has been implicated in cancer cell proliferation and survival.
An orally bioavailable, small-molecule, dihydrogen phosphate prodrug of the pyrazoloquinazoline Aurora kinase inhibitor AZD1152-hydroxyquinazoline pyrazol anilide (AZD1152-HQPA) with potential antineoplastic activity. Upon administration and rapid conversion from the prodrug form in plasma, AZD1152-HQPA specifically binds to and inhibits Aurora kinase B, which results in the disruption of spindle checkpoint functions and chromosome alignment and, so, the disruption of chromosome segregation and cytokinesis. Consequently, cell division and cell proliferation are inhibited and apoptosis is induced in Aurora kinase B-overexpressing tumor cells. Aurora kinase B, a serine/threonine protein kinase that functions in the attachment of the mitotic spindle to the centromere, is overexpressed in a wide variety of cancer cell types.
An orally bioavailable integrase strand-transfer inhibitor (INSTI), with activity against human immunodeficiency virus type 1 (HIV-1) infection. Upon oral administration, dolutegravir binds to the active site of integrase, an HIV enzyme that catalyzes the transfer of viral genetic material into human chromosomes. This prevents integrase from binding to retroviral deoxyribonucleic acid (DNA), and blocks the strand transfer step, which is essential for the HIV replication cycle. This prevents HIV-1 replication.
An orally bioavailable pan inhibitor of human fibroblast growth factor receptors (FGFRs) with potential antiangiogenic and antineoplastic activities. Infigratinib selectively binds to and inhibits the activities of FGFRs, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation, and the induction of tumor cell death. FGFRs are a family of receptor tyrosine kinases which may be upregulated in various tumor cell types and may be involved in tumor cell differentiation and proliferation, tumor angiogenesis, and tumor cell survival.
A class of vitamin E compounds naturally found in many different sources, such as oils, nuts, and vegetables. Tocopherols have antioxidant activity.
An enzyme isolated from the bacterium Erwinia chrysanthemi (E. carotovora). Asparagine is critical to protein synthesis in leukemic cells, which cannot synthesize this amino acid due to the absence of the enzyme asparagine synthase. Asparaginase hydrolyzes L-asparagine to L-aspartic acid and ammonia, thereby depleting leukemic cells of asparagine and blocking protein synthesis and tumor cell proliferation, especially in the G1 phase of the cell cycle. This agent also induces apoptosis in tumor cells. The Erwinia-derived product is often used for those patients who have experienced a hypersensitivity reaction to the E. Coli formulation.
Iron (II,III) oxide (Fe3O4). It is a black ore of IRON that forms opaque crystals and exerts strong magnetism.
A proprietary formulation consisting of a Phellodendron amurense (Amur cork tree) bark extract, often used in traditional Chinese medicine, with anti-inflammatory, anti-oxidant and potential chemopreventive and antineoplastic activities. Phellodendron amurense bark extract contains certain isoquinoline alkaloids, flavone glycosides and phenolic compounds. Upon administration of Phellodendron amurense bark extract, the various phytochemicals in this formulation modulate multiple signal transduction pathways. This agent appears to block the activation of the transcription factor cAMP response binding protein (CREB) and inhibits Akt signaling, thereby inhibiting tumor cell growth and inducing apoptosis in Akt- and CREB-overexpressing cancer cells. In addition, this agent inhibits cyclooxygenase type 2 (COX-2), nuclear factor kappa b (NF-kB) and tumor necrosis factor alpha (TNF-a)-mediated signaling; COX-2, NF-kB and TNF-a are upregulated in certain types of cancer and during inflammation.
Tearing eyes; a condition caused either by tear overproduction or impaired drainage of the tear duct. Causes of tear overproduction include eye irritation (e.g., eye infection, foreign body in the eye), headache, pain reaction, allergies, sinusitis, and injury to the eye.
A question about how frequently an individual's voice difficulties restrict their personal and social life.
A question about how frequently an individual's voice makes them feel handicapped.
A question about how frequently an individual's voice problem causes them to lose income.
A question about how frequently an individual's voice problem upsets them.
A question about how frequently the clarity of an individual's voice is unpredictable.
A question about how frequently an individual feels as though they have to strain to produce voice.
A question about how frequently an individual feels left out of conversation because of their voice.
The first significant event which ultimately led to death.
The second significant event which ultimately led to death.
An abnormal finding indicating that the level of a particular hormone is not within the expected normal values.
Intractable juvenile myoclonic epilepsy which is not associated with an acute, prolonged epileptic crisis.
Typical atrial flutter is an organised atrial tachycardia. It can also be defined as a macroreentrant tachycardia confined to the right atrium. This arrhythmia has a 200-260 ms cycle length, although it may fluctuate depending on patient's previous treatment or ablation, congenital heart disease, etc. Ventricular rate response will be limited by the atrioventricular node conductions, usually presenting a 2:1 or 3:1 response, during atrial flutter. Typical (counter clockwise) flutter is associated with the common flutter pattern: a regular continuous undulation with dominant negative deflections in inferior leads II, III and aVF, often described also as a saw tooth pattern, and flat atrial deflections in leads I and aVL. Atrial deflections in V1 can be positive, biphasic or negative. [PMID:28835836]
A broad spectrum of other macroreentrant tachycardias in which the wave front does not travel around the tricuspid annulus. Atypical atrial flutter originates from the left atrium or areas in the right atrium (such as surgical scars) and has a variable appearance on ECG in regards to the flutter waves.
A type of astigmatism in which an unequal curvature of the cornea and some cases additionally of the lens causes one meridian of the eye to be hyperopic (farsighted) and a second meridian that is perpendicular to the first to be myopic (nearsighted). [ORCID:0000-0003-0986-4123]
Astigmatism in which the refractive power of the vertical meridian is the greatest. [ORCID:0000-0003-0986-4123]
Nephrotic syndrome, occurring in the pediatric population, in which proteinuria does not normalize with administration of steroids; this condition is unresponsive to a minimum of four weeks administration of oral corticosteroids.
Indicates a person who has smoked at least 100 cigarettes in his or her lifetime and who currently smokes every day.
Potential for subsequent admission to a hospital or other health care institution for treatment
Two or more concurrent chronic physical, mental, or behavioral health problems in an individual.
Characterized by irregular macular hyperpigmentation of the oral mucosa.
Occlusal scheme that requires localised adjunctive therapy.
Occlusal scheme that requires reestablishment, but without any change in vertical dimension of occlusion.
Occlusal scheme that requires reestablishment with changes in the vertical dimension of occlusion.
Occlusal scheme in dentate patient that requires localised adjunctive therapy.
Occlusal scheme in dentate patient that requires reestablishment, but without any change in vertical dimension of occlusion.
Occlusal scheme in dentate patient that requires reestablishment with changes in the vertical dimension of occlusion.
Occlusal scheme in partially dentate patient that requires localised adjunctive therapy.
Occlusal scheme in partially dentate patient that requires reestablishment, but without any change in vertical dimension of occlusion.
Occlusal scheme in partially dentate patient that requires reestablishment with changes in the vertical dimension of occlusion.
A supernumerary tooth resembling a molar tooth especially in shape.
HSD10 mitochondrial disease most commonly presents as an X-linked neurodegenerative disorder with highly variable severity and age at onset ranging from the neonatal period to early childhood. The features are usually multisystemic, consistent with mitochondrial dysfunction. Some affected males have a severe infantile form associated with cardiomyopathy that may result in death in early childhood, whereas other rare patients may have juvenile onset or even atypical presentations with normal neurologic development. More severely affected males show developmental regression in infancy or early childhood, often associated with early-onset intractable seizures, progressive choreoathetosis and spastic tetraplegia, optic atrophy or retinal degeneration resulting in visual loss, and mental retardation. Heterozygous females may show non-progressive developmental delay and intellectual disability, but may also be clinically normal. Although the diagnosis can be aided by the observation of increased urinary levels of metabolites of isoleucine breakdown (2-methyl-3 hydroxybutyrate and tiglylglycine), there is not a correlation between these laboratory features and the phenotype. In addition, patients do not develop severe metabolic crises in the neonatal period as observed in other organic acidurias, but may show persistent lactic acidosis, most likely reflecting mitochondrial dysfunction (summary by Rauschenberger et al., 2010; review by Zschocke, 2012). In a review of the disorder, Zschocke (2012) noted that although this disorder was originally thought to be an inborn error of branched-chain fatty acid and isoleucine metabolism resulting from decreased HSD17B10 dehydrogenase activity (HSD17B10 'deficiency'), subsequent studies have shown that the HSD17B10 gene product has additional functions and also acts as a component of the mitochondrial RNase P holoenzyme, which is involved in mitochondrial tRNA processing and maturation and ultimately mitochondrial protein synthesis. The multisystemic features of HSD10MD most likely result from the adverse effect of HSD17B10 mutations on mitochondrial function, rather than from the effects on the dehydrogenase activity (see PATHOGENESIS below).
A local or systemic infection associated with the use of a hemodialysis catheter.
47,XYY syndrome is characterized by an extra copy of the Y chromosome in each of a male's cells. Although many males with this condition are taller than average, the chromosomal change sometimes causes no unusual physical features. Most males with 47,XYY syndrome have normal production of the male sex hormone testosterone and normal sexual development, and they are usually able to father children.47,XYY syndrome is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Affected boys can have delayed development of motor skills (such as sitting and walking) or weak muscle tone (hypotonia). Other signs and symptoms of this condition include hand tremors or other involuntary movements (motor tics), seizures, and asthma. Males with 47,XYY syndrome have an increased risk of behavioral, social, and emotional difficulties compared with their unaffected peers. These problems include attention deficit hyperactivity disorder (ADHD); depression; anxiety; and autism spectrum disorder, which is a group of developmental conditions that affect communication and social interaction.Physical features related to 47,XYY syndrome can include increased belly fat, a large head (macrocephaly), unusually large teeth (macrodontia), flat feet (pes planus), fifth fingers that curve inward (clinodactyly), widely spaced eyes (ocular hypertelorism), and abnormal side-to-side curvature of the spine (scoliosis). These characteristics vary widely among affected boys and men.
Benzoic acids, salts, or esters that contain an amino group attached to carbon number 4 of the benzene ring structure.
A derivative of nitrofuran used as an antibiotic in the treatment of urinary tract infections. Nifurtoinol is bactericidal to most gram-positive and gram-negative urinary tract pathogens.
The beta subunit of follicle stimulating hormone. It is a 15-kDa glycopolypeptide. Full biological activity of FSH requires the non-covalently bound heterodimers of an alpha and a beta subunit. Mutation of the FSHB gene causes delayed puberty, or infertility.
Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare immunodeficiency syndrome, characterized by a narrow vulnerability to poorly virulent mycobacteria, such as bacillus Calmette-Guérin (BCG) vaccines and environmental mycobacteria (EM), and defined by severe, recurrent infections, either disseminated or localized.
A malignant neoplasm that arises from a pre-existing lower grade lesion, or as a result of a primary lesion that has spread to secondary sites, or due to a complication of a cancer treatment.
A rare, autosomal dominant inherited syndrome caused by mutations in the PAX3, MITF, and SNAI2 genes. Signs and symptoms include hearing loss, dystopia canthorum (widely spaced inner corners of the eyes), and changes in the color of the skin, hair, and eyes.
A water-soluble, synthetic small molecule with potential antineoplastic activity. Cenisertib selectively binds to and inhibits aurora kinases (AKs), a family of serine-threonine kinases which are important regulators of cell division and proliferation, and which are overexpressed in certain types of cancer. Inhibition of aurora kinases inhibits cell division and proliferation and induces apoptosis in tumor cells overexpressing AKs.
A change in the nucleotide sequence of the HRAS gene.
A molecular genetic abnormality that refers to mutation of the c-kit (CD117) proto-oncogene. It is associated with the development of gastrointestinal stromal tumor and gastrointestinal autonomic nerve tumor. It has also been described in acute myeloid leukemias, dysgerminomas, and seminomas.
A change in the nucleotide sequence of the EGFR gene.
A molecular genetic abnormality indicating the presence of a mutation in the PTEN gene on chromosome 10q23.3.
A disorder of the blood that is present at birth.
A rare form of idiopathic inflammatory myopathy with clinical manifestation of acute or subacute proximal muscle weakness and histopathological features of myocyte necrosis and regeneration without significant inflammation. The main presenting feature is subacute severe symmetrical proximal myopathy with a markedly elevated creatine kinase level. The course is often severe but may be self-limiting and recovery may occur within weeks to months of discontinuing the causative agent, if identified. The disease is thought to be related to an immune response possibly triggered by drug therapy, connective tissue diseases, or cancer. The exact mechanism underling the disorder is not known but some autoantibodies appear to be a likely cause. Malignancy may be involved.
Virus-associated trichodysplasia spinulosa is a rare infectious skin disease characterized by the development of follicular papules with keratin spicules in various parts of the body, predominantly in the face (e.g. nose, eyebrows, auricles), that is due to polyomavirus infection in immunocompromized patients.
Psychogenic movement disorders (PMD) are movement disorders that cannot be attributed to any known structural or neurochemical diseases, but represent the manifestation of an underlying psychiatric illness or malingering. Most cases of PMD fall in the psychiatric diagnostic category of conversion disorders of the motor subtype.
Inability to effectively digest or absorb the components of breast milk substitutes. Symptoms may include emesis, abdominal distension or diarrhea.
Syndrome with characteristics of sagittal craniosynostosis, hydrocephalus, Chiari I malformation and radioulnar synostosis. Other clinical findings include blepharophimosis, small low-set ears, hypoplastic philtrum, kidney malformation, and hypogenitalism. The syndrome was described in two brothers from a non-consanguineous family. No causative mutation has been identified so far.
An iodine 131-radiolabeled small-molecule benzamide compound with potential antineoplastic activity. The benzamide moiety of 131-I-MIP-1145 binds to melanin, selectively delivering a cyotoxic dose of gamma and beta radiation to melanin-expressing tumor cells. Melanin pigments, polymer derivatives of the amino acid tyrosine, are over-expressed in approximately 40% of melanomas.
The coronary sinus / left ventricular lead was not implanted because a lead had been previously implanted. (ACC)
The cardiac lead has been left in situ and reused. (ACC)
Evidence of severe retrograde blood flow through the valve(s) of the heart. (ACC)
The cardiac valve orifice is abnormally narrow, to a severe degree. (ACC)
An electrocardiographic finding of ventricular tachycardia that occurs without provocation and does not resolve without intervention.
A sudden loss of consciousness with loss of postural tone not related to anesthesia with high risk characteristics. High risk characteristics include non-ischemic dilated cardiomyopathy, or ischemic heart disease with significant ventricular dysfunction, hypertrophic cardiomyopathy, Brugada Syndrome, or Long QT Syndrome. (ACC)
An electrocardiographic finding of ventricular tachycardia accompanied by syncope in the individual.
There was greater than or equal to 50% stenosis (reduction in cross-sectional area) in three coronary arteries (or greater than or equal to 50% stenosis in the left main coronary artery and greater than or equal to 50% stenosis in the right coronary artery). (ACC)
Deep, poorly localized chest or arm discomfort that is reproducibly associated with physical exertion or emotional stress and is relieved promptly (i.e., in less than 5 minutes) with rest and/or the use of sublingual nitroglycerin. Some patients may have no chest discomfort but present solely with jaw, neck, ear, arm, shoulder, back, or epigastric discomfort or with unexplained dyspnea without discomfort. If these symptoms have a clear relationship to exertion or stress or are relieved promptly with nitrates, they should be considered equivalent to angina. J Am Coll Cardiol, 2007; 50:1-157, doi:10.1016/j.jacc.2007.02.013 (Published online 6 August 2007). (ACC)
The coronary sinus / left ventricular lead was not implanted because the operator was unable to obtain acceptable pacing thresholds. (ACC)
The coronary sinus / left ventricular lead was not implanted because the operator was unable to obtain satisfactory coronary sinus access. (ACC)
The coronary sinus / left ventricular lead was not implanted because the operator was unable to obtain satisfactory vascular access. (ACC)
The coronary sinus / left ventricular lead was not implanted because the coronary sinus was dissected. (ACC)
The coronary sinus / left ventricular lead was not implanted because the operator was unable to position the lead in the tributary vein of the coronary sinus. (ACC)
An episode of cardiac arrest or arrhythmia where the etiology was unknown. (ACC)
The movement (macroscopic or microscopic) of an existing lead within the heart or vascular tree away from the original implantation site. (ACC)
An electrocardiographic finding of ventricular tachycardia or ventricular fibrillation of unknown cause. (ACC)
Discrete (less than 10 mm length) and concentric and readily accessible and non-angulated segment less than 45 degrees and smooth contour and little or no calcification and less than totally occlusive and not ostial in location and no major branch involvement and absence of thrombus. (ACC)
Tubular (10-20 mm length) or eccentric or moderate tortuosity of proximal segment or moderately angulated segment, 45-90 degrees or irregular contour or moderate to heavy calcification or ostial in location or bifurcation lesions requiring double guidewires or some thrombus present or total occlusion less than 3 months old. (ACC)
Diffuse (length greater than 2cm) or excessive tortuosity of proximal segment or extremely angulated segments greater than 90 degrees or total occlusions greater than 3 months old and/or bridging collaterals or inability to protect major side branches or degenerated vein grafts with friable lesions. (ACC)
No perfusion: No antegrade flow beyond the point of occlusion. (www.TIMI.org accessed 21SEP2011) (ACC)
Penetration without perfusion: The contrast material passes beyond the area of obstruction, but fails to opacify the entire coronary bed distal to the obstruction for the duration of the cine run. (www.TIMI.org accessed 21SEP2011) (ACC)
Partial reperfusion: The contrast material passes across the obstruction and opacifies the entire coronary bed distal to the obstruction. However, the rate of entry of contrast into the vessel distal to the obstruction and/or its rate of clearance from the distal bed are perceptibly slower than its entry into and/or clearance from comparable areas not perfused by the culprit vessel (e.g., the opposite coronary artery or coronary bed proximal to the obstruction).(www.TIMI.org accessed 21SEP2011) (ACC)
Complete perfusion: Antegrade flow into the bed distal to the obstruction occurs as promptly as into the bed proximal to the obstruction and clearance of contrast material from the involved bed is as rapid as from an uninvolved bed in the same vessel or the opposite artery. (www.TIMI.org accessed 21SEP2011) (ACC)
Renal cell carcinoma that develops in patients who are long-term survivors of childhood neuroblastoma.
An electrocardiographic finding that the cardiac rhythm is initiated by a cardiac pacemaker generated electrical impulse in the ventricle. Intrinsic ventricular complexes are absent.
Pathologic material in a vessel that obstructs myocardial perfusion. (ACC)
Characteristics of coronary lesions that contribute to procedural risk during coronary intervention.
A tear within the wall of a coronary vein. (ACC)
A blood clot (thrombus) in the lumen of the carotid artery. (ACC)
Fifty percent or greater stenosis within an existing stent. (ACC)
A measure of procedural success during a percutaneous coronary intervention when a guidewire can be deployed across a coronary artery lesion. (ACC)
The contribution of blood supply from the right or left vessel system to the posterior descending artery. (ACC)
A recombinant, subunit herpes zoster (HZ) vaccine containing varicella-zoster virus (VZV) glycoprotein E (gE), that can potentially be used to prevent HZ infection, also called shingles. Upon administration, HZ vaccine GSK1437173A stimulates the host immune system to induce both specific CD4-positive T-cells and antibodies against VZV gE, thereby protecting against infection with HZ. VZV gE, the most common antigen in VZV viral particles, plays a key role in VZV infection. Compared to live-attenuated vaccines, the subunit vaccine prevents the risk of vaccine-induced HZ in immunocompromised patients.
A non-neoplastic hamartomatous polyp that arises from the colon and rectum. It is characterized by the presence of smooth muscle branching bands, and cystic mucosal changes.
A radioconjugate consisting of the tyrosine-containing somatostatin analog Tyr3-octreotate (TATE) conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and radiolabeled with the beta-emitting radioisotope lutetium Lu 177, with potential imaging and antineoplastic activities. Lutetium Lu 177 dotatate binds to somatostatin receptors (SSTRs), with high affinity to type 2 SSTR, present on the cell membranes of many types of neuroendocrine tumor (NET) cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR-positive cells. Tyr3-octreotate (TATE) is an octreotide derivative in which phenylalanine at position 3 is substituted by tyrosine and position 8 threoninol is replaced with threonine. SSTRs have been shown to be present in large numbers on NET and their metastases, while most other normal tissues express low levels of SSTRs.
A term that refers to a TNM finding of a primary tumor limited to the site of growth and indicates microinvasion only.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the stomach.
Problem with the amount of output energy needed to cause cardiac depolarization being higher than expected/desired.
Problem with the amount of output energy needed to cause cardiac depolarization being unstable.
Problem associated with the device ceasing to deliver paces.
Problem associated with the results of a test or measurement not appearing.
Handling of the device not in accordance with specification, prior to use on the patient.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the stomach. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the stomach. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the stomach. It is characterized by the presence of malignant large cells.
A carcinoma that arises from the stomach and is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
A marine-derived, synthetically produced compound with potential antineoplastic activity. DNA minor groove-binding agent PM060184 covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death.
An orally bioavailable inhibitor of signal transducer and activator of transcription 3 (STAT3), with potential antineoplastic activity. STAT3 inhibitor OPB-51602 inhibits the phosphorylation and thus the activation of STAT3 protein, impeding STAT3 protein from translocating from the cytoplasm to the nucleus and thereby blocking STAT3's regulation of gene expression through direct binding to the promoters of responsive genes. STAT3 regulates the cellular functions that lead to the cancer phenotype, and constitutive activation of STAT3 is observed in a wide range of human cancers, inducing uncontrolled proliferation and neoplastic transformation.
A synthetic version, known as PIF-1, of the peptide Preimplantation Factor (PIF), an embryo-secreted peptide, with potential activity against Graft-versus-Host Disease (GVHD). PIF-1 is believed to have wide-ranging activity on the immunologic system, including a whole host of immunologic changes that resemble pregnancy, in which there is neither graft-versus-host or host-versus-graft disease between the mother and the embryo. Replication of the immunologic profile of pregnancy through the administration of PIF-1 may thus benefit patients undergoing bone marrow transplant (BMT) who experience graft-versus-host disease (GVHD). Native embryonic PIF has been found to have a multi-targeted effect on various aspects of the immune system, coordinated so that there is a successful embryonic implantation and a successful pregnancy.
A proprietary preparation of polymeric nanoparticles containing the second-generation taxane docetaxel, targeted to prostate-specific membrane antigen (PSMA), with antineoplastic activity. PSMA-targeted docetaxel nanoparticles BIND-014 carry docetaxel within a matrix of polylactic acid covered with a coating of polyethylene glycol; embedded on the surface of the polyethylene glycol coating are ligands targeted to PSMA. BIND-014 allows gradual release of docetaxel upon degradation of the polylactic acid, and the PEG encapsulation escapes the host immune response while PSMA ligands on the surface restrict the cytotoxic effect to PSMA-expressing cells. Docetaxel binds to and stabilizes the beta-tubulin subunit, thereby inhibiting microtubule disassembly which results in cell-cycle arrest at the G2/M phase and cell death. PSMA is a cell-surface antigen that is abundantly present on the surface of cancer cells and on the neovasculature that feeds a wide variety of tumor types.
A carbazole derivative (3,6-bis[2-(1-methylpyridinium)vinyl]carbazole diiodide) that selectively targets to the G-quadruplex DNA structure, used as a fluorescent probe for cancer cytological diagnosis and with potential antitumor activity. G-quadruplex stabilizer BMVC, preferentially uptaken by cancer cells, binds to and stabilize the telomeric G-quadruplex structure at the end of DNA; when visualized with fluorescent imaging device, BMVC emits bright fluorescent light and can be used to differentiate tumor cells from normal cells. The BMVC/G-quadruplex complexes also interfere with the activity of telomerase, which is highly active in tumor cells and plays a key role in tumorigenesis while expressed at very low levels in most somatic cells.
A potent, specific inhibitor of the canonical Wnt signaling pathway in cancer stem cells with potential antineoplastic activity. Wnt signaling pathway inhibitor PRI-724 specifically inhibits the recruiting of beta-catenin with its coactivator CBP (the binding protein of the cAMP response element-binding protein CREB); together with other transcription factors beta-catenin/CBP binds to WRE (Wnt-responsive element) and activates transcription of a wide range of target genes of Wnt/beta-catenin signaling. Blocking the interaction of CBP and beta-catenin by this agent prevents gene expression of many proteins necessary for growth, thereby potentially suppressing cancer cell growth. The Wnt/beta-catenin signaling pathway regulates cell morphology, motility, and proliferation; aberrant regulation of this pathway leads to neoplastic proliferation.
A gastrointestinal stromal tumor arising from the stomach. It is characterized by a maximum diameter equal or less than 5 cm and no more than 5 mitotic figures per 50 high power fields.
An orally available small molecule dual inhibitor targeting human vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs) with antiangiogenic and antineoplastic activities. VEGFR/PDGFR dual kinase inhibitor X-82 inhibits all isoforms of VEGFR and PDGFR, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation, and the induction of tumor cell death. Both VEGFRs and PDGFRs are receptor tyrosine kinases that may be upregulated in various tumor cell types. VEGFR/PDGFR dual kinase inhibitor X-82 has been shown to reduce tissue toxicity by 95 percent compared with first-generation kinase inhibitors.
A gastrointestinal stromal tumor arising from the stomach. It is characterized by large size (diameter greater than 10 cm) or more than 5 mitotic figures per 50 high power fields.
A gastrointestinal stromal tumor arising from the stomach. It is characterized by a maximum diameter greater than 5 cm and equal or less than 10 cm and no more than 5 mitotic figures per 50 high power fields.
A rare synovial sarcoma that arises from the stomach.
A rare glomus tumor that arises from the stomach. It is seen in adults, especially women. The majority of cases follow a benign clinical course.
A rare schwannoma that arises from the stomach. It follows a benign clinical course.
A rare soft tissue neoplasm arising from the stomach. It occurs in the antrum and pyloric region and it may extend into the duodenum. It occurs in all ages and affects men and women equally. Morphologically it is characterized by a multinodular plexiform mass that involves the muscular layer. The neoplastic cells are spindle-shaped and the mitotic activity is low. It follows a benign clinical course.
A premalignant neoplastic and dysplastic lesion that arises from the ampulla of Vater. It is characterized by the absence of invasion. This category includes intestinal-type adenomas, noninvasive papillary neoplasms of pancreatobiliary type, and flat intraepithelial neoplasia.
An orally active prodrug of torcitabine (L-deoxycytidine), a nucleoside analog with activity against hepatitis B virus. Torcitabine is modified in vivo to its triphosphate form and acts as a competitive inhibitor of viral DNA polymerase.
An exophytic, preinvasive, papillary epithelial neoplasm that arises from the ampulla of Vater. Histologically it resembles the papillary neoplasms of the biliary tree. This category includes neoplasms with low grade dysplasia and high grade dysplasia.
An ampullary noninvasive papillary neoplasm of the pancreatobiliary type characterized by the presence of low grade dysplasia.
An ampullary noninvasive papillary neoplasm of the pancreatobiliary type characterized by the presence of high grade dysplasia.
The anhydrous form of tezacitabine, a synthetic pyrimidine nucleoside analogue with potential antineoplastic activity. Phosphorylated by cellular kinases, tezacitabine is converted into its active diphosphate and triphosphate metabolites. Tezacitabine diphosphate binds to and irreversibly inhibits the activity of the enzyme ribonucleotide reductase (RNR), which may result in the inhibition of DNA synthesis in tumor cells and eventually tumor cell apoptosis. Tezacitabine triphosphate acts as a substrate for DNA polymerase, thereby further inhibiting DNA replication. RNR catalyzes the conversion of ribonucleoside 5'-diphosphates to deoxyribonucleoside 5'-diphosphates, a necessary step for DNA synthesis, and is overexpressed in many tumor cell types.
A non-polypoid, preinvasive neoplasm that arises from the ampulla of Vater. It is characterized by the presence of high grade dysplasia.
A regional lymph node TNM finding indicating that there is no evidence of regional lymph node metastasis histologically, and immunohistochemistry is negative.
A regional lymph node TNM finding indicating that there are malignant cells in regional lymph node(s) no greater than 0.2 mm and are detected by hematoxylin and eosin stain or immunohistochemistry.
A regional lymph node TNM finding indicating that there is no evidence of regional lymph node metastasis histologically and molecular analysis (RT-PCR) is negative.
A regional lymph node TNM finding indicating that there is no evidence of regional lymph node metastasis histologically and by immunohistochemistry, but the molecular analysis (RT-PCR) is positive.
A regional lymph node TNM finding indicating that there is metastasis to 1-3 nodes. The metastasis is greater than 2 mm and all are less than 20 mm.
A regional lymph node TNM finding indicating that there is metastasis to four or more nodes. The metastasis is greater than 2 mm and all are less than 20 mm.
A regional lymph node TNM finding indicating that the tumor extends beyond the lymph node capsule and is less than 20 mm.
A regional lymph node TNM finding indicating that the metastases to the lymph nodes are more than 20 mm.
A regional lymph node TNM finding indicating the presence of micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm).
A distant metastasis TNM finding indicating that there is no evidence of distant metastasis clinically or by radiologic studies, but there are small numbers of cells detected by special studies in the blood and bone marrow, or there is tiny metastasis (no larger than 0.2 mm) detected in nonregional lymph nodes.
An invasive adenocarcinoma that arises from the ampulla of Vater. It is characterized by the presence of malignant cells that resemble the malignant cells of the pancreatic ductal or extrahepatic bile duct carcinomas.
A morphologic finding indicating the presence of malignant cells with a phenotype that resembles the malignant cells of the pancreatic ductal or extrahepatic bile duct carcinomas.
A rare variant of undifferentiated carcinoma that arises from the ampulla of Vater. It is characterized by the presence of non-neoplastic, histiocytic, osteoclast-like multinucleated giant cells.
A very rare adenocarcinoma that arises from the ampulla of Vater. It is usually of the intestinal type and is characterized by the presence of malignant polygonal cells with abundant eosinophilic cytoplasm resembling hepatocytes.
An invasive adenocarcinoma that arises from an exophytic papillary neoplasm of the ampulla of Vater.
A neoplasm with neuroendocrine differentiation that arises from the ampulla of Vater and periampullary region. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the ampulla of Vater and periampullary region.
A well differentiated, low grade tumor with neuroendocrine differentiation that arises from the ampulla of Vater and the periampullary region. The mitotic count is less than 2 per 10 HPF.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the ampulla of Vater and the periampullary region. The mitotic count is 2-20 per 10 HPF.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the ampulla of Vater and the periampullary region. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma. Patients usually present with advanced stage disease.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the ampulla of Vater and the periampullary region. It is characterized by the presence of malignant large cells.
A carcinoma that arises from the ampulla of Vater and the periampullary region. It is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
A well differentiated neuroendocrine tumor that arises from the ampulla of Vater and the periampullary region. It produces serotonin.
A well differentiated neuroendocrine tumor that arises from the ampulla of Vater and the periampullary region. It produces somatostatin.
An extra-adrenal paraganglioma that arises from the ampulla of Vater and the periampullary region. It consists of a mixture of neuroendocrine cells, Schwann-like cells, and ganglion cells.
An immunohistochemical test result indicating that there are neoplastic cells stained positive with the p16 INK4a monoclonal antibody.
A rare, primary marginal zone lymphoma of mucosa-associated lymphoid tissue that arises from the meningeal dura. The majority of cases have been described in middle aged women. Radiologically, the lymphomatous dural infiltration mimics meningioma.
A term that refers to a TNM finding of a primary, non-invasive, papillary cancer.
An orally available nutritional supplement and proprietary formulation containing extracts from the sea cucumber, sea sponge, shark fin, sea urchin and the marine grass Sargassum, with potential antioxidant, antitumor, anti-angiogenic and immunomodulating activities. TBL-12 contains various amino acids, minerals, vitamins and omega-3 fatty acids.
A nanoparticle-based injectable concentrate containing the water-insoluble taxane paclitaxel, with potential antineoplastic activity. Upon reconstitution and administration, paclitaxel binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. Compared to paclitaxel alone, the nanodispersion-based formulation uses less toxic solvents and allows for administration of higher doses resulting in higher concentrations of paclitaxel at the tumor site, and an increased safety profile.
An antibody-targeted lipidic nano-carrier containing the antineoplastic anthracycline antibiotic doxorubicin encapsulated within liposomes, and conjugated to a monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), with potential antitumor activity. Upon administration of HER2-targeted liposomal doxorubicin hydrochloride MM-302, the immunoliposome allows for specific delivery of doxorubicin to tumors overexpressing the HER2 receptor. Once inside the HER2-expressing tumor cells, doxorubicin intercalates into DNA and interferes with topoisomerase II activity, thereby inhibiting DNA replication and RNA synthesis. Compared to doxorubicin alone or liposomal doxorubicin, targeted liposomal delivery of doxorubicin improves efficacy while lowering the toxicity profile. HER2, a tyrosine kinase receptor, is overexpressed in many cancer cell types.
A cancer vaccine consisting of a peptide derived from the melanocyte differentiation antigen Melan-A (or MART-1) and the human leukocyte antigen HLA-DP4-restricted human melanoma antigen 3 (MAGE-3.DP4), with potential immunostimulating and antineoplastic activities. Upon administration, Melan-A/MAGE-3.DP4 peptide vaccine may stimulate the immune system to mount a cytotoxic T-cell (CTL) response against tumor cells expressing Melan-A and MAGE-3, resulting in tumor cell lysis. The tumor associated antigens Melan-A and MAGE-3 are overexpressed in a variety of cancer cell types.
A peptide cancer vaccine consisting of peptides derived from the melanoma antigen NA-17, the human leukocyte antigen HLA-A2-restricted human melanoma antigen 3 (MAGE-3.A2) and the cancer-testis antigen (NY-ESO-1), with potential immunostimulating and antineoplastic activities. Upon administration, the NA-17/MAGE-3.A2/NY-ESO-1 peptide vaccine may stimulate the immune system to mount a cytotoxic T-cell (CTL) response against tumor cells expressing NA-17, MAGE-3.A2 and NY-ESO-1, resulting in tumor cell lysis. The tumor-associated antigens (TAAs) NA-17, MAGE-3.A2 and NY-ESO-1 are overexpressed in a variety of cancer cell types.
A non-neoplastic hamartomatous polyp that arises from the small intestine. It is characterized by the presence of tortuous and cystically dilated glands, edematous changes, and inflammation.
A B-cell non-Hodgkin lymphoma that arises from the small intestine. Representative examples include diffuse large B-cell lymphoma, mucosa-associated lymphoid tissue lymphoma, alpha heavy chain disease/immunoproliferative small intestinal disease, Burkitt lymphoma, follicular lymphoma, and mantle cell lymphoma.
A T-cell non-Hodgkin lymphoma that arises from the small intestine. It includes the enteropathy-associated T-cell lymphoma and the monomorphic CD56 positive intestinal T-cell lymphoma.
A diffuse large B-cell lymphoma that arises from the small intestine.
A follicular lymphoma that arises from the small intestine. It most often affects the duodenum.
A small intestinal high grade B-cell lymphoma with blastoid features or features between diffuse large B-cell lymphoma and Burkitt lymphoma which lacks MYC, BCL2, and BCL6 rearrangements.
A primary small intestinal T-cell non-Hodgkin lymphoma of intraepithelial T-lymphocytes. It is characterized by the presence of a monomorphic cellular infiltrate of small to medium sized T lymphocytes that are cytotoxic and express CD56. It is not associated with celiac disease.
A Kaposi sarcoma that arises from the small intestine.
An angiosarcoma that arises from the small intestine.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the small intestine.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the small or large intestine.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the small or large intestine. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the small intestine. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the small intestine. It is characterized by the presence of malignant large cells.
A carcinoma that arises from the small intestine and is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the small intestine. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
An extra-adrenal paraganglioma that arises from the small intestine. Unlike the conventional paragangliomas, this tumor has a peculiar morphologic appearance; it consists of a mixture of epithelial cells, spindle cells, and ganglion cells.
A neoplasm with neuroendocrine differentiation that arises from the colon or rectum. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the colon or rectum. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the colon or rectum. It is characterized by the presence of malignant large cells.
A carcinoma that arises from the colon or rectum and is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the colon or rectum.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the colon or rectum. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A neuroendocrine tumor that arises from the colon or rectum and produces glucagon-like peptides. Morphologically, it is characterized by the presence of neoplastic cells forming tubular or trabecular patterns.
A well differentiated neuroendocrine tumor that arises from the colon or rectum and produces serotonin.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the colon or rectum. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the small or large intestine. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the digestive system. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
A morphologic finding indicating the presence of occasional macrophages in a tissue sample.
Chronic cholecystitis not associated with the presence of gallstones.
A morphologic finding indicating the replacement of part of the columnar epithelium by intestinal-type epithelium.
A morphologic finding indicating the presence of darkly stained macrophages that contain melanin.
The deposition of hyaline material in the wall of the efferent arterioles.
A morphologic finding indicating the presence of epithelial changes in a tissue sample that result from a pathologic process.
A morphologic finding indicating the presence of fibroblastic hyperplasia in a tissue sample.
A finding indicating the presence of a focal ulcerated lesion that is associated with hemorrhage.
The deposition of hyaline material in the wall of the arterioles.
A morphologic finding indicating the presence of a neutrophilic infiltrate within the mucosa of a tissue sample.
A morphologic finding indicating the presence of a malignant cellular infiltrate invading the muscularis mucosa.
An orally available, potent, selective inhibitor of dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. Compared to vildagliptin, anagliptin caused longer lasting inhibition of DPP-4 activity.
A cyst located at the periphery of the meniscus.
A microscopic finding indicating the absence of neoplastic cells in a tissue sample.
A lesion that is located in the serosa surface of an organ.
A morphologic finding indicating the presence of inflammatory cells in the connective tissue that surrounds groups of muscle fibers (perimysium) and the connective tissue that surrounds individual muscle fibers (endomysium).
A morphologic finding indicating the presence of eosinophils scattered in the interstitial spaces of a tissue sample.
A morphologic finding indicating the presence of hemosiderin deposits in the stroma of a tissue sample.
A morphologic finding indicating the presence of a collagen band under the epithelial layer in a tissue sample.
Hyperparakeratosis of the oral mucosa caused by chronic tobacco use. It manifests as oral leukoplakia.
A replication-incompetent adenovirus encoding E. coli purine nucleoside phosphorylase (Ad/PNP) used as a prodrug activating agent. Administered intratumorally, Ad/PNP expresses the enzyme PNP, which may catalyze systematically administrated fludarabine phosphate prodrug into its active form 2-fluoroadenine (F-Ade). F-Ade inhibits DNA polymerase alpha, ribonucleotide reductase and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth. Localized prodrug activation provides targeted chemotherapy, thereby potentially reducing systemic side effects.
A humanized IgG4 monoclonal antibody against the semaphorin 4D (SEMA4D; CD100) with potential immunomodulating and antineoplastic activities. Upon administration, anti-SEMA4D monoclonal antibody VX15/2503 binds to and neutralizes SEMA4D, thereby preventing binding of SEMA4D to its receptor plexin-B1 (PLXNB1). By blocking the interaction of SEMA4D and PLXNB1, VX15/2503 may cause an inhibition of endothelial cell activation and migration, eventually leading to an inhibition of angiogenesis and tumor cell proliferation. Semaphorin 4D, a large cell surface antigen found on the resting T-cell and overexpressed in a variety of tumor cell types, plays an important role in vascular growth, tumor progression, invasion and immune cell regulation.
A small molecule integrin receptor antagonist (IRA) with potential antineoplastic activity. Upon administration, GLPG0187 binds to and blocks the activity of 5 RGD-integrin receptor subtypes, including alphavbeta1, alphavbeta3, alphavbeta5, alphavbeta6 and alpha5beta1. This may result in the inhibition of endothelial cell-cell interactions and endothelial cell-matrix interactions, and the prevention of angiogenesis and metastasis in tumor cells expressing these integrin receptors. Integrin receptors are transmembrane glycoproteins expressed on the surface of tumor vessel endothelial cells and some types of cancer cells, and play a crucial role in endothelial cell adhesion and migration.
A reactive inflammatory disorder affecting the urethra. It is characterized by the development of small cysts in the urethral wall. The cysts are lined by urothelial cells and metaplastic glandular cells.
A reactive inflammatory disorder affecting the urethra. It is characterized by the development of small cysts in the urethral wall. The cysts are lined by urothelial cells.
A reactive inflammatory disorder affecting the urethra. It is characterized by the development of small cysts in the urethral wall. The cysts are lined by metaplastic glandular cells.
A small molecule and orally available inhibitor of colony-stimulating factor-1 receptor (CSF1R; cFMS) with potential antineoplastic activity. cFMS tyrosine kinase inhibitor ARRY-382 binds to and inhibits the activity of cFMS. By preventing colony-stimulating factor-1 (CSF-1)-cFMS signaling, this agent may inhibit tumor cell proliferation in cFMS-overexpressing tumor cells. cFMS, a tyrosine kinase receptor, is overexpressed in certain tumor cell types and plays an essential role in macrophage differentiation and regulation of cell proliferation.
A reactive inflammatory disorder affecting the bladder. It is characterized by the development of small cysts in the bladder wall. The cysts are lined by urothelial cells and metaplastic glandular cells.
A nutritional supplement containing an extract of the skin of Muscadine grape (Vitis rotundifolia), with anti-inflammatory, antioxidant and potential chemopreventive activities. The skin extract of the muscadine grape contains numerous phytochemicals including hydrolyzable tannins and flavonoids, such as anthocyanin 3,5-diglucosides, quercetin, myricetin, and kaempferol glycosides. Upon administration, muscadine grape skin extract (MSKE) appears to inhibit PI3K/Akt and MAPK signaling, eventually leading to apoptosis and a reduction in tumor cell proliferation.
A mouthwash containing 5% dexpanthenol, the alcoholic analogue of the dextrorotatory isomer of pantothenic acid with potential antimucositis activity. Although the exact mechanism remains to be elucidated, upon rinsing with this solution dexpanthenol is converted to pantothenic acid (vitamin B5) which is required for coenzyme A synthesis as well as for the metabolism of proteins, carbohydrates, and fats. Coenzyme A is involved in fatty acids and sphingolipids synthesis crucial for cell membrane integrity. This mouthwash may have a protective and healing effect on the oral mucosa, may improve hydration and may potentially prevent or reduce radiation/chemotherapy-induced mucositis.
A radioconjugate and an acetate analog labeled with fluorine F 18 ((18)F-FAC), a positron-emitting isotope, with potential prostate tumor tracer property using positron emission tomography (PET). Although the mechanism of action is unclear, fluorine F 18 acetate preferentially accumulates in tumor tissue, serving as a tracer for imaging tumors with PET. Fluorine 18 has a longer radioactive half-life (110 min) vs. the half-life of carbon-11 acetate (20.4 min). Furthermore, (18)F-FAC showed a rapid clearance from liver and extensive excretion to bile and urine in comparison with carbon-11 acetate, therefore this tracer may be a useful alternative to C-11 acetate for the detection of prostate tumors by PET.
A morphologic finding indicating the presence of extensive injury of the alveolar pneumocytes in a lung tissue sample.
A morphologic finding indicating enlargement of the glomeruli in a kidney specimen.
A morphologic finding indicating the presence of fine granular yellowish-brownish pigment within the cytoplasm of the cells in a tissue sample.
A molecular abnormality referring to the loss of at least one copy of the PTEN gene (10q23).
A molecular genetic abnormality indicating the presence of a mutation in the PI3KCA (phosphatidyl inositol 3-kinase) gene on chromosome 3q26.32.
A zinc-containing form of rosuvastatin, a hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor with antilipidemic activity.
A morphologic finding referring to the presence of a vacuolated area that surrounds the nucleus. It results from nuclear shrinking.
Intraluminal hyperplasia of endothelial cells, encircling the entire lumen.
A morphologic finding that refers to delicate vascular channel formations. It is characterized by the formation of arborizing and curving capillaries.
A morphologic finding referring to the presence of multiple foci of serpentine necrosis and glial cell perivascular pseudopalisading in a glioma.
A morphologic finding that refers to the accumulation of glial cells encircling neurons and/or vessels in a tissue specimen.
A morphologic finding that refers to the presence of ectopic gray matter in a tissue sample.
A morphologic finding that refers to the presence of ectopic white matter in a tissue sample.
A morphologic finding that refers to the presence of a small cell component in a cellular infiltrate.
A morphologic finding referring to the presence of a cellular infiltrate that is composed of cells with perinuclear cytoplasmic halos, resembling oligodendrocytes.
A conjugate vaccine of meningococcal polysaccharide used for active immunization against invasive meningococcal disease caused by Neisseria meningiditis serogroups A, C, Y, and W-135.
A vaccine containing acellular antigenic components of Bordetella pertussis adsorbed on a mineral carrier with active immunizing activity against pertussis infection.
A vaccine that contains live attenuated influenza virus (LAIV) particles. This vaccine is administered intranasally for influenza prophylaxis. Not all populations are good candidates for LAIV; the very young, elderly, asthmatics and those with health impaired may be better treated with the trivalent inactivated vaccine that is administered intramuscularly.
A viral infection that occurs during infancy, childhood or adolescence.
A group of congenital or acquired disorders that affect the normal development of the brain.
A polyp that arises from the appendix. It is characterized by the presence of serrated glands and the absence of generalized dysplasia.
A non-neoplastic polyp that arises from the appendix. It is characterized by the presence of elongated serrated crypts and the absence of atypia or dysplasia.
A morphologic finding indicating the presence of dysplasia throughout a cellular component in a tissue sample.
A precancerous intraepithelial neoplastic lesion that affects the appendix. It is characterized by low or high grade dysplasia of the mucosal epithelium. There is no evidence of invasion.
A precancerous intraepithelial neoplastic lesion that affects the appendix. It is characterized by the presence of mild dysplasia and mild architectural alterations of the mucosal epithelium. There is no evidence of invasion.
A precancerous intraepithelial neoplastic lesion that affects the appendix. It is characterized by the presence of moderate or severe dysplasia and complex architectural alterations of the mucosal epithelium. There is no evidence of invasion.
A mucinous adenocarcinoma that arises from the appendix. The malignant cells are numerous and exhibit high grade dysplasia. It may be associated with pseudomyxoma peritonei, but unlike the low grade mucinous neoplasm, it invades other organs and metastasizes to distant anatomic sites.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the appendix.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the appendix. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
A well differentiated neuroendocrine tumor arising from the wall of the appendix. It is characterized by the presence of neoplastic cells forming round solid nests and occasionally glandular structures. The majority of the cases are asymptomatic, and they are found incidentally in appendectomy specimens. The majority of the tumors are located in the distal end of the appendix and they are enterochromaffin-cell carcinoid tumors producing serotonin. Most cases show morphologic evidence of appendiceal wall and lymphatic vessel invasion by tumor cells. Despite the morphologic evidence of invasion, appendiceal carcinoid tumors only infrequently produce lymph node or distant metastases.
A topical gel containing a cell permeable hydrophilic piperidine nitroxide with potential radioprotective and antioxidant activity. As a stable, free radical compound, MTS-01 may be able to protect cells against the damaging effects of reactive oxygen species (ROS), upon exposure to ionizing radiation and oxidative stress. The topically applied MTS-01 may protect normal tissue from radiation-induced toxicity, such as radiation dermatitis, during radiation therapy.
A recombinant human-mouse chimeric monoclonal antibody against human tissue factor (TF), with potential antiangiogenic, anticoagulant and anti-inflammatory activities. Upon administration, anti-TF monoclonal antibody ALT-836 binds to TF or the TF-Factor VIIa (FVIIa) complex preventing binding and activation of Factor X (FX) and Factor IX (FIX). This may prevent thrombin formation and cancer-associated venous thromboembolism, and may inhibit angiogenesis and tumor cell proliferation. TF, a transmembrane protein and procoagulant, is overexpressed in many tumor cell types, and is correlated with metastasis, angiogenesis, tumor growth and tumor-associated thrombosis.
An orally available, nonsteroidal selective estrogen receptor (ER) alpha agonist with potential antineoplastic activity. Upon administration of GTx-758, this agent suppresses the secretion of the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the pituitary gland through feedback inhibition. In males, the inhibition of LH secretion prevents the synthesis of androgens, including testosterone, by the testes. This may result in suppressed total serum testosterone to the levels observed in castration.
A rare Kaposi sarcoma that arises from the appendiceal wall.
A neuroma that arises from the appendix. It is characterized by a neural spindle cell proliferation that replaces the appendiceal mucosa and lymphoid tissue. It usually results in the obliteration of the appendiceal lumen.
An adenoma that arises from the rectum. It is characterized by prominent serration of the glands and the presence of generalized low-grade dysplasia.
A polyp that arises from the colon. It is characterized by the presence of serrated glands and the absence of generalized dysplasia. Some authors have suggested that it is a precursor lesion for some colonic adenocarcinomas with microsatellite instability.
A polyp that arises from the rectum. It is characterized by the presence of serrated glands and the absence of generalized dysplasia. Some authors have suggested that it is a precursor lesion for some adenocarcinomas with microsatellite instability.
A traditional serrated adenoma characterized by the presence of prominent villous projections of the neoplastic epithelium.
A morphologic finding indicating the presence of prominent, thin, elongated projections of the neoplastic glandular epithelium in the colorectal mucosa.
A traditional serrated adenoma that arises from the colon or rectum. It is characterized by the presence of prominent villous projections of the neoplastic epithelium.
A term that refers to a group of polypoid lesions in the colon and rectum that are characterized by the presence of serrated architecture of the epithelial component. This group includes hyperplastic polyps, traditional serrated adenomas, and sessile serrated adenomas/polyps.
The presence of multiple serrated polyps in the colon. The polyps are predominantly sessile serrated adenomas/polyps. A minority of the polyps are microvesicular variants of hyperplastic polyps. According to some authors, the polyps are proximal to the sigmoid colon. According to others, the polyps are distributed throughout the entire colon.
A serrated hyperplastic polyp that arises from the colon and rectum. It is characterized by the presence of goblet cells and the absence of microvacuolated columnar cells. There is no evidence of epithelial atypia or dysplasia.
A serrated hyperplastic polyp that arises from the colon and rectum. It is characterized by the presence of small cells in the crypts that do not contain mucin. Reactive epithelial atypia may be present.
A serrated hyperplastic polyp that arises from the colon and rectum. It is characterized by the presence of microvacuolated columnar cells that are admixed with small numbers of goblet cells. There is no evidence of epithelial atypia or dysplasia.
A non-neoplastic, hamartomatous polyp that arises from the colon and rectum. This group includes the juvenile polyp, Peutz-Jeghers polyp, and Cowden-associated polyp.
A non-neoplastic, hamartomatous polyp that arises from the stomach, small intestine, and large intestine. This group includes the juvenile polyps and Peutz-Jeghers polyps.
A hamartomatous polyp that arises from the colon and rectum and it is associated with the presence of Cowden syndrome.
A usually polypoid neoplasm that arises from the glandular epithelium of the rectal mucosa. It is characterized by a tubular architectural pattern. The neoplastic glandular cells have dysplastic features.
A polypoid adenoma that arises from and protrudes into the lumen of the colon or rectum. Epithelial dysplasia is always present. According to the architectural pattern it is classified as tubular, tubulovillous, or villous.
A polypoid adenoma that arises from and protrudes into the lumen of the rectum. Epithelial dysplasia is always present. According to the architectural pattern it is classified as tubular, tubulovillous, or villous.
The concurrent presence of three copies each of chromosomes 4 and 10.
A rare, invasive colorectal adenocarcinoma characterized by the presence of a malignant infiltrate with serrated glandular architecture.
A rare, invasive colon adenocarcinoma characterized by the presence of a malignant infiltrate with serrated glandular architecture.
A rare, invasive rectal adenocarcinoma characterized by the presence of a malignant infiltrate with serrated glandular architecture.
A rare, invasive colorectal adenocarcinoma characterized by the presence of malignant cribriform glands with central necrotic changes.
A rare, invasive colon adenocarcinoma characterized by the presence of malignant cribriform glands with central necrotic changes.
A rare, invasive rectal adenocarcinoma characterized by the presence of malignant cribriform glands with central necrotic changes.
A rare, invasive colorectal adenocarcinoma characterized by the presence of clusters of malignant glandular cells within stromal spaces.
A rare, invasive colon adenocarcinoma characterized by the presence of clusters of malignant glandular cells within stromal spaces.
A rare, invasive rectal adenocarcinoma characterized by the presence of clusters of malignant glandular cells within stromal spaces.
A biphasic colorectal carcinoma with a spindle cell, sarcomatoid component.
A term that refers to raised and dysplastic large intestinal lesions in patients with a history of ulcerative colitis. Grossly, these lesions present as polyps, plaques, or patches in areas affected by ulcerative colitis. The presence of these lesions is associated with the development of adenocarcinomas. Colectomy is indicated when they are detected.
A colorectal adenocarcinoma that develops in patients with a history of ulcerative colitis. Such carcinomas are usually multiple and flat. Histologically, they are usually mucinous or signet-ring cell type.
A colorectal adenocarcinoma that develops in patients with a history of Crohn disease.
An extranodal lymphoma that arises from the colon or rectum. The majority are B-cell non-Hodgkin lymphomas.
An extranodal non-Hodgkin lymphoma that arises from the colon or rectum. The majority are B-cell non-Hodgkin lymphomas.
An extranodal Hodgkin lymphoma that arises from the colon or rectum.
A colorectal high grade B-cell lymphoma with blastoid features or features between diffuse large B-cell lymphoma and Burkitt lymphoma which lacks MYC, BCL2, and BCL6 rearrangements.
A rare Burkitt lymphoma that arises from the colon or rectum.
A diffuse large B-cell lymphoma that arises from the colon or rectum.
A diffuse large B-cell lymphoma that arises from the colon. It is the most frequent type of lymphoma found in the colon.
A mantle cell lymphoma that arises from the colon or rectum. It often presents as a polypoid lesion.
An extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue that arises from the colon or rectum.
A malignant soft tissue neoplasm that arises from the colon or rectum. Representative examples include angiosarcoma, Kaposi sarcoma, and leiomyosarcoma.
An aggressive malignant smooth muscle neoplasm that arises from the colon or rectum. It is characterized by a proliferation of neoplastic spindle cells.
A Kaposi sarcoma that arises from the colon or rectum.
An angiosarcoma that arises from the colon or rectum.
A schwannoma that arises from the colon or rectum. It may cause gastrointestinal bleeding and luminal obstruction.
A perineurioma that arises from the colon or rectum. It usually presents as a small sessile polyp.
A ganglioneuroma that arises from the colon or rectum. It usually presents as a small mucosal polyp.
A benign granular cell tumor that arises from the colon or rectum. It usually presents as a mucosal nodule and is detected incidentally by endoscopy.
A polysaccharide vaccine used to prevent contraction of meningococcal meningitis.
An autosomal recessive hereditary neoplastic syndrome caused by mutations in the MUTYH gene on chromosome 1p34.1. It is characterized by the presence of multiple colorectal polyps that may progress to carcinoma. Development of gastric and small intestinal polyps may also occur.
A molecular genetic abnormality that refers to the mutation of the MUTYH gene on chromosome 1p34.1.
A molecular genetic abnormality that refers to the mutation of the BMPR1A (bone morphogenetic protein receptor, type 1A) gene on chromosome 10q22.3.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the anal canal.
An orally active, tetrahydropyrimidin-2(1H)-one derivative and inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Letaxaban does not affect bleeding time.
The tosylate salt form of edoxaban, an orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Edoxaban is administered as edoxaban tosylate. This agent has an elimination half-life of 9-11 hours and undergoes renal excretion.
A well differentiated, low grade tumor with neuroendocrine differentiation that arises from the anal canal. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the anal canal. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the anal canal. It is characterized by the presence of malignant small cells.
A carcinoma that arises from the anal canal. It is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
A benign epithelial neoplasm that arises from the anal canal. It is characterized by a papillary growth pattern and a proliferation of neoplastic squamous cells without morphologic evidence of malignancy.
A non-radiological determination of disease progression based on symptoms or other findings.
An assessment of the overall response of the disease to the therapy.
An overall level of substantial worsening in non-target disease that is of a magnitude that, even in the presence of SD or PR in target disease, the treating physician would feel it important to change therapy. (RECIST)
A non-neoplastic polypoid lesion that arises from the anal transitional zone. It is characterized by the presence of hyperplastic rectal mucosa that is partially covered by squamous or transitional epithelium.
A benign neoplasm arising from the perianal sweat glands. It presents as a cystic nodular lesion and is characterized by the presence of cystic and papillary structures. The papillary structures contain connective tissue and are covered by two layers of epithelium.
Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker levels above the normal limits. (RECIST)
An ethylsulfonyl derivative of arotinoic acid with differentiation inducing and potential antineoplastic activities. Like other retinoic acid agents, etarotene binds to and activates retinoic acid receptors (RARs), thereby inducing changes in the expression of certain genes leading to cell differentiation and decreased cell proliferation in susceptible cells.
A synthetic, phenolic hydroxyl retinoid with proapoptotic activity. As an atypical retinoid, adarotene has the ability to induce apoptosis which is independent of retinoid receptor signaling.
Problem associated with the device failing to be activated including expansion.
A non-neoplastic disorder that affects the gallbladder. Representative examples include cholecystitis and adenomyomatosis.
A liquid, oromucosal formulation containing a muscarinic agonist with potential anti-xerostomia activity. Upon application to the inside lining of the mouth, muscarinic agonist APD515 may locally act on muscarinic receptors on the salivary glands and may stimulate the production of saliva thereby relieving dryness of the mouth.
A recombinant vaccine containing a genetically detoxified adenylate cyclase toxin (CyaA) of Bordetella pertussis coupled, through its catalytic site, to the melanoma tyrosinase A2 epitope YMDGTMSQV, with potential antineoplastic activity. Via the toxin moiety, the recombinant B. pertussis adenylate cyclase toxin-tyrosinase A2 epitope specifically binds to the alphaMbeta2 integrin (CD11b/CD18) located on CD11b-positive antigen-presenting cells (APC). Upon processing and presentation of the melanoma-specific epitope by MHC class I molecules to the surface of these APCs, a specific cytotoxic T-cell (CTL) response against tumor cells expressing tyrosinase may be initiated, resulting in decreased tumor growth and cell lysis.
A population of autologous cytotoxic T lymphocytes (CTLs) with potential immunomodulating and antitumor activities. White blood cells are grown ex-vivo and are exposed to dendritic cells (DCs) loaded with lymphoma tumor associated antigens (TAAs); the TAA-specific CTLs are further expanded ex-vivo before being introduced into the patient. Upon infusion with TAA-specific CTLs, these CTLs may help activate tumor-specific CTL responses in the patient, thereby specifically killing TAA-expressing cancer cells and eventually inhibiting tumor cell proliferation.
A fusion DNA vaccine containing the first domain of fragment C (FrC) of tetanus toxin (TT865-1120) (p.DOM) fused to the human Wilms' Tumor gene-1 (WT1)-derived MHC class I-binding epitope WT1.37, with potential antitumor activity. Upon vaccination with p.DOM-WT1-37 DNA and subsequent electroporation, this vaccine may induce a WT1 epitope-specific cytotoxic T-lymphocyte (CTL) response against WT1 expressing cells, resulting in cell lysis and inhibition of cancer cell proliferation in WT1-overexpressing cancer cells. WT1, a tumor associated antigen, is overexpressed in most types of leukemia and in a variety of solid cancers. The FrC of tetanus toxin contains the MHC II-binding sequence, p30, which induces T-helper cell activation for long-lasting immunity.
A fusion DNA vaccine containing the first domain of fragment C (FrC) of tetanus toxin (TT865-1120) (p.DOM) fused to the human Wilms' Tumor gene-1 (WT1)-derived MHC class I-binding epitope WT1.126, with potential antitumor activity. Upon vaccination with p.DOM-WT1-126 DNA and subsequent electroporation, this vaccine may induce a WT1 epitope-specific cytotoxic T-lymphocyte (CTL) response against WT1 expressing cells, resulting in cell lysis and inhibition of cancer cell proliferation in WT1-overexpressing cancer cells. WT1, a tumor associated antigen, is overexpressed in most types of leukemia and in a variety of solid cancers. The FrC of tetanus toxin contains the MHC II-binding sequence, p30, which induces T-helper cell activation for long-lasting immunity.
A cancer vaccine containing autologous dendritic cells (DCs) that are transfected with mRNAs extracted from amplified ovarian cancer stem cells, and mRNAs of the universal tumor antigens human telomerase reverse transcriptase (hTERT) and survivin with potential immunostimulatory and antineoplastic activities. Upon administration, ovarian cancer stem cell/hTERT/survivin mRNAs-loaded autologous DC-006 vaccine may elicit a highly specific cytotoxic T-cell (CTL) response against ovarian cancer cells expressing hTERT, survivin, and specific ovarian cancer stem cell antigens. hTERT, the catalytic subunit of human telomerase, and survivin, a member of the inhibitor of apoptosis (IAP) family of proteins, may be upregulated in certain tumor cell types, playing key roles in tumor cell growth and survival. Ovarian cancer stem cells contain a specific range of antigens that are essential for the neoplastic growth and survival of ovarian cancer cells.
A recombinant, chimeric human fusion protein consisting of the iC3b/C3d-binding region of human complement receptor type 2 (CR2/CD21) linked to the alternative complement pathway (ACP) inhibitory domain of human factor H (fH) (CR2-fH), with potential complement system inhibiting activity. Via its C3 binding domain, TT30 selectively binds to complement activated cell surfaces and via its fH binding domain regulates ACP activity. This suppresses excessive complement activity and may result in an inhibition of ACP-mediated hemolysis of paroxysmal nocturnal hemoglobinuria (PNH) red blood cells (RBCs) as well as preventing ACP-induced tissue damage. Factor H is a key regulator in the activation of ACP.
A population of allogeneic lymphocytes expressing the CD56 surface antigen and exhibiting a lack of CD3, with immunomodulating activity. Upon infusion of allogeneic CD56-positive CD3-negative natural killer (NK) cells, these cells are able to secrete cytokines and recognize and kill tumor cells as well as virally-infected cells. CD56 is a transmembrane glycoprotein also known as NCAM (Neural Cell Adhesion Molecule).
A locked nucleic acid (LNA)-based antisense oligonucleotide targeting the androgen receptor (AR) mRNA, with potential antineoplastic activity. Upon administration, EZN-4176 is hybridized and releases the complementary sequences of AR mRNA, thereby blocking translation of the AR protein and inhibiting AR-induced tumor cell growth and promoting tumor cell apoptosis in AR-overexpressing tumor cells. AR is overexpressed in certain breast and prostate cancers and is involved in tumor cell proliferation and survival. LNAs contain a methylene bridge linking 2'-oxygen and 4'-carbon of ribose sugar rings, thereby increasing their thermal stability and decreasing degradation.
A neutralizing antibody against the prolactin receptor (PRLR) with potential antineoplastic activity. Upon administration, anti-prolactin receptor antibody LFA102 binds to PRLR and prevents the binding of the peptide hormone prolactin (PRL) to its receptor. This binding induces an antibody-dependent cellular cytotoxicity (ADCC) and may eventually prevent tumor cell proliferation in PRLR-positive cancer cells. PRLR/PRL signaling pathway is frequently overexpressed in breast and prostate cancer.
The succinate salt form of cevipabulin, a synthetic, water soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin binds at the vinca-binding site on tubulin, but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. This stabilizes tubulin and prevents microtubule disassembly. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.
A non-metastasizing neoplasm that arises from the hepatocytes or intrahepatic bile ducts. Representative examples include hepatocellular adenoma and bile duct adenoma.
A hepatocellular adenoma caused by inactivating mutations of the HNF1A gene. It is characterized by the presence of lobulated contours, steatosis, and absence of inflammation or nuclear atypia.
A hepatocellular adenoma caused by activating mutations of beta-catenin. It is characterized by the presence of nuclear atypia and absence of inflammation or steatosis. There is an increased risk of malignant transformation.
A hepatocellular adenoma that occurs more often in women. It is characterized by increased levels of inflammation-associated proteins. It is usually associated with steatosis and obesity.
A hepatocellular adenoma without distinguished morphologic characteristics or known molecular abnormalities.
A molecular genetic abnormality indicating the presence of inactivating mutation of the HNF1A (hepatocyte nuclear factor 1-alpha) gene.
A premalignant neoplastic lesion of the liver. It is characterized by the presence of hepatocytes with decreased cell volume, increased nuclear/cytoplasmic ratio, basophilia, mild nuclear pleomorphism, and hyperchromasia.
A hepatic dysplastic nodule characterized by the presence of high grade atypical cellular changes.
A hepatic dysplastic nodule characterized by the presence of low grade atypical cellular changes.
A low grade, well-differentiated, early stage hepatocellular carcinoma. Grossly, it usually presents as a nodular lesion that measures less than 2 cm in diameter.
An extremely rare neoplasm with neuroendocrine differentiation that arises from the liver. It includes well differentiated neuroendocrine tumors (carcinoid tumors) and poorly differentiated neuroendocrine carcinomas.
An extremely rare, aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the liver.
A rare type of hepatocellular carcinoma characterized by the presence of pleomorphic malignant cells that are intermixed with lymphocytes.
A hepatocellular carcinoma characterized by the presence of malignant cells with mild atypia and an increased nuclear/cytoplasmic ratio forming thin trabecular patterns. It is usually associated with small tumors and an early stage.
A hepatocellular carcinoma characterized by the presence of malignant cells with abundant eosinophilic cytoplasm forming trabecular and pseudoglandular patterns. It is usually associated with tumors that are larger than 3 cm in diameter.
A hepatocellular carcinoma characterized by the presence of malignant pleomorphic cells forming solid patterns.
An orally available inhibitor of the nuclear enzymes poly(ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon administration, ABT-767 selectively binds to PARP 1 and 2, thereby preventing repair of damaged DNA via the base excision repair (BER) pathway. This agent enhances the accumulation of DNA strand breaks and promotes genomic instability eventually leading to apoptosis. ABT-767 may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell chemo- and radioresistance. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and can be activated by single strand DNA (ssDNA) breaks.
An orally bioavailable benzamide and inhibitor of human class I histone deacetylases (HDACs) isoenzymes 1, 2 and 3, with potential antineoplastic activity. HDAC inhibitor 4SC-202 selectively binds to and inhibits class I HDACs leading to an accumulation of highly acetylated histones. This may result in an induction of chromatin remodeling, the selective transcription of tumor suppressor genes, and the tumor suppressor protein-mediated inhibition of tumor cell division and eventually the induction of tumor cell apoptosis. This may inhibit tumor cell proliferation in susceptible tumor cells. HDACs, upregulated in many tumor types, are a class of enzymes that deacetylate chromatin histone proteins.
A monoclonal antibody directed against the Wnt signaling pathway with potential antineoplastic activity. Upon administration, vantictumab binds to certain receptors in the Wnt signaling pathway thereby preventing the activation of the Wnt signaling pathway. This may result in an inhibition of cancer stem cell (CSC) activity and a subsequent inhibition of cancer cell proliferation. The Wnt signaling pathway is dysregulated in many cancer cell types and appears to play a major role in CSC regulation and activity; CSC are tumor initiating cells that are able to self-renew and are responsible for tumor growth and resistance.
An orally available small molecule and platelet thrombopoietin (TPO) receptor (TPOR; MPL) agonist with potential megakaryopoiesis stimulating activity. Upon administration, TPOR agonist ONO-7746 binds to and stimulates TPOR, which may lead to the proliferation and differentiation of megakaryocytes. In turn, this may increase the production of blood platelets and may prevent chemotherapy induced thrombocytopenia (CIT). TPOR is a cytokine receptor and member of the hematopoietin receptor superfamily.
A monoclonal antibody directed against colony stimulating factor 1 receptor (CSF1R) with potential antineoplastic activity. CSF1R monoclonal antibody IMC-CS4 binds to CSF1R which may trigger antitumoral antibody-dependent cell-mediated cytotoxicity (ADCC) in tumor cells overexpressing CSF1R. CSF1R, also known as macrophage colony-stimulating factor receptor (M-CSFR) and CD115 (Cluster of Differentiation 115), is a cell-surface receptor for its ligand colony stimulating factor 1 (CSF1); this receptor is overexpressed or mutated in certain tumor cell types and plays major roles in tumor cell proliferation and metastasis.
A topical cream containing urea and 0.1% vitamin K1 (phytomenadione) with topical epidermal growth factor receptor (EGFR)-activating activity. Upon application of vitamin K1-containing urea skin cream, vitamin K1 may locally activate EGFR, thereby abrogating EGFR inhibition in the skin caused by systemic EGFR inhibiting agents. This may help inhibit the acne-like skin rash induced by EGFR antagonists. EGFR, a tyrosine kinase, plays a key role in maintaining epidermal integrity.
An intrahepatic cholangiocarcinoma that arises from the intrahepatic large bile ducts.
An intrahepatic cholangiocarcinoma that arises from the small interlobular bile ducts.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the intrahepatic or extrahepatic bile ducts. It is characterized by the presence of mild epithelial atypia.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the intrahepatic or extrahepatic bile ducts. It is characterized by the presence of moderate epithelial atypia.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the intrahepatic or extrahepatic bile ducts. It is characterized by the presence of severe epithelial atypia.
A papillary epithelial neoplasm that arises from the epithelium of the intrahepatic or extrahepatic bile ducts and it is associated with an invasive carcinomatous component. For intraductal papillary neoplasms of the intrahepatic bile ducts, the carcinomatous component is an intrahepatic cholangiocarcinoma; for intraductal papillary neoplasms of the extrahepatic bile ducts, the carcinomatous component is an adenocarcinoma.
A rare benign neoplasm that arises from the intrahepatic bile ducts. It is characterized by the presence of biliary epithelial tissue and fibroblastic stroma.
A rare malignant tumor that arises from the liver and occurs in children. It is characterized by the presence of nested epithelioid and spindle cells. Desmoplasia, calcifications, and bone formation may also be present.
A non-invasive mucinous cystic neoplasm that arises from the intrahepatic or extrahepatic bile ducts. It is characterized by the presence of mild atypia.
A non-invasive mucinous cystic neoplasm that arises from the intrahepatic or extrahepatic bile ducts. It is characterized by the presence of moderate atypia.
A non-invasive mucinous cystic neoplasm that arises from the intrahepatic or extrahepatic bile ducts. It is characterized by the presence of severe atypia.
A capillary hemangioma that arises from the liver. It occurs in infants and children.
A rare lymphangioma that arises from the liver. It usually occurs in children and adolescents.
Multiple lymphangiomas that affect the liver and other anatomic sites. Although histologically benign, diffuse lymphangiomatosis that affects the liver and multiple organs has a poor prognosis.
A synovial sarcoma that affects the liver.
A rare, aggressive primary malignant tumor of the liver that occurs in childhood. It is characterized by the presence of a diffuse infiltrate of undifferentiated cells with rhabdoid features.
A benign or malignant extragonadal germ cell tumor that arises from the liver. Representative examples include teratoma and yolk sac tumor.
A yolk sac tumor that arises from the liver.
A non-neoplastic disorder that affects the liver, bile ducts, and gallbladder. Representative examples include hepatitis, cirrhosis, cholangitis, and cholecystitis.
A molecular genetic abnormality indicating the presence of a sensitizing mutation in the epidermal growth factor receptor-tyrosine kinase inhibitor domain.
A molecular genetic abnormality indicating the presence of resistance in the epidermal growth factor receptor-tyrosine kinase inhibitor domain, due to secondary mutations of the EGFR gene.
A molecular genetic abnormality indicating the presence of multiple copies of the PIK3CA (phosphatidyl inositol 3-kinase) gene.
A molecular genetic abnormality indicating the presence of mutations in the AKT family of genes. This family includes the AKT1, AKT2, and AKT3 genes that are located on chromosomes 14, 19, and 1, respectively.
A molecular genetic abnormality indicating the presence of a mutation in the ERBB2 gene on chromosome 17q12.
A molecular genetic abnormality indicating the presence of multiple copies of the PDGFRA (platelet-derived growth factor receptor, alpha polypeptide) gene.
A condition in children in which bones become soft and deformed because they don't have enough calcium and phosphorus. It is caused by not having enough vitamin D in the diet or by not getting enough sunlight. In adults, this condition is called osteomalacia.
The cholinate salt form of rosiglitazone, an agent belonging to the glitazone class of antidiabetic agents with antihyperglycemic and anti-inflammatory activities. In addition to its ability to lower blood glucose levels, rosiglitazone also exerts anti-inflammatory activity through its ability to inhibit nuclear factor-kappaB (NF-KB) activity and increase I-kappaB levels. In addition, rosiglitazone may cause fluid retention and may worsen congestive heart failure. This agent is also associated with an increased risk of heart attacks.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the gallbladder. It is characterized by the presence of mild epithelial atypia.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of gallbladder. It is characterized by the presence of moderate epithelial atypia.
A non-invasive, papillary epithelial neoplasm that arises from the epithelium of the gallbladder. It is characterized by the presence of severe epithelial atypia.
An epithelial, usually multiloculated neoplasm arising from the gallbladder. It occurs predominantly in females. Signs and symptoms include abdominal mass, abdominal pain, and jaundice. Morphologically, the cystic spaces are lined by columnar epithelium and contain mucinous or serous fluid.
A non-invasive mucinous cystic neoplasm that arises from the gallbladder epithelium. It is characterized by the presence of mild atypia.
A non-invasive mucinous cystic neoplasm that arises from the gallbladder epithelium. It is characterized by the presence of moderate atypia.
A non-invasive mucinous cystic neoplasm that arises from the gallbladder epithelium. It is characterized by the presence of severe atypia.
A mucinous cystic neoplasm that arises from the gallbladder and it is associated with an invasive carcinomatous component.
A rare variant of gallbladder adenocarcinoma. It is characterized by the presence of a malignant glandular epithelial infiltrate with a cribriform growth pattern.
A well or moderately differentiated adenocarcinoma that arises from the gallbladder. It is the most common type of gallbladder carcinoma and is characterized by the presence of malignant tubular glands. Intestinal differentiation may be present.
An unusual, well differentiated adenocarcinoma that arises from the gallbladder. It is characterized by the presence of tall malignant columnar cells with mucin-containing cytoplasm and basally located nuclei.
A neoplasm with neuroendocrine differentiation that arises from the gallbladder. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the gallbladder.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the gallbladder. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
A well differentiated, low grade neuroendocrine tumor (carcinoid tumor) that arises from the gallbladder. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the gallbladder. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
A carcinoma that arises from the gallbladder and is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
An invasive mixed adenoneuroendocrine carcinoma of the gallbladder characterized by the presence of neoplastic signet-ring cells resembling goblet cells of the intestine.
A neuroendocrine tumor that arises from the gallbladder. It does not show the morphologic characteristics of typical carcinoid tumors (neoplastic cells forming solid nests). In contrast, the tumor cells form small discrete tubules.
The ceribate ester form of paclitaxel, a compound extracted from the Pacific yew tree Taxus brevifolia with antineoplastic activity. Paclitaxel binds to and stabilizes tubulin thereby inhibiting the disassembly of microtubules, resulting in the inhibition of cell division. This agent also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein B-cell Leukemia 2 (BCL2).
A well or moderately differentiated adenocarcinoma that arises from the extrahepatic bile ducts. It is characterized by the presence of malignant tubular glands.
An unusual, well differentiated adenocarcinoma that arises from the extrahepatic bile ducts. It is characterized by the presence of tall malignant columnar cells with mucin-containing cytoplasm and basally located nuclei.
A neoplastic, non-invasive lesion that affects the extrahepatic bile duct epithelium. It is characterized by the presence of atypical epithelial cells with an increased nuclear/cytoplasmic ratio, nuclear hyperchromasia, and loss of nuclear polarity.
A neoplastic, non-invasive lesion that affects the intrahepatic bile duct epithelium. It is characterized by the presence of atypical epithelial cells with an increased nuclear/cytoplasmic ratio, nuclear hyperchromasia, and loss of nuclear polarity.
A neoplastic, non-invasive lesion that affects the intrahepatic or extrahepatic bile duct epithelium. It is characterized by the presence of atypical epithelial cells with an increased nuclear/cytoplasmic ratio, nuclear hyperchromasia, and loss of nuclear polarity.
A mucinous cystic neoplasm that arises from the extrahepatic bile ducts and it is associated with an invasive carcinomatous component.
A papillary epithelial neoplasm that arises from the epithelium of the extrahepatic bile ducts and it is associated with an invasive carcinomatous component. The carcinomatous component is an adenocarcinoma.
A papillary epithelial neoplasm that arises from the epithelium of the intrahepatic bile ducts and it is associated with an invasive carcinomatous component. The carcinomatous component is an intrahepatic cholangiocarcinoma.
A lymphoma that arises from the extrahepatic bile ducts, with the bulk of the disease located at this site.
A neoplasm with neuroendocrine differentiation that arises from the extrahepatic bile ducts. It includes well differentiated neuroendocrine tumors (low and intermediate grade) and poorly differentiated neuroendocrine carcinomas (high grade).
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the extrahepatic bile ducts.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the extrahepatic bile ducts. The mitotic count is more than 20 per 10 HPF. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
A well differentiated, intermediate grade tumor with neuroendocrine differentiation that arises from the extrahepatic bile ducts. The mitotic count is 2-20 per 10 HPF and/or the Ki67 index is 3 to 20 percent.
A carcinoma that arises from the extrahepatic bile ducts and is characterized by the presence of a malignant glandular epithelial component and a malignant neuroendocrine component. At least 30 percent of either component should be present for the diagnosis to be made.
A unit of a pharmaceutical product intended to promote the use of the drug and not intended for sale.
A pentavalent vaccine comprised of the epitope antigens of the ganglioside lactones GD2L and GD3L, Globo H hexasaccharide 1 (Globo H), fucosyl GM1 and N-propionylated polysialic acid conjugated with the immunostimulant keyhole limpet hemocyanin (KLH), with potential immunostimulating and antineoplastic activity. Vaccination with the pentavalent KLH conjugate vaccine may induce production of IgG and IgM antibodies as well as an antibody-dependent cell-mediated cytotoxicity (ADCC) against tumors expressing any of these antigens. The antigens included in the pentavalent KLH conjugate vaccine are upregulated in a variety of cancer cells. KLH, a natural protein isolated from the marine mollusk keyhole limpet, is an immunostimulant carrier protein.
Human autologous T-lymphocytes transduced with a retroviral vector encoding a T cell receptor (TCR) specific for the human melanoma antigen A3 (MAGE-A3), with potential antineoplastic activity. Upon isolation, transduction, expansion ex vivo, and reintroduction into the patient, the MAGE-A3 reactive TCR-transduced autologous T cells bind to tumor cells expressing MAGE-A3, which may halt the growth of MAGE-A3-expressing cancer cells; the TCR is specific for MAGE-A3:168-176.
Autologous chimeric immune receptor (CIR) T cells transfected with anti-mesothelin chimeric T cell receptor mRNA, with potential antineoplastic activity. The anti-mesothelin mRNA encodes a single chain antibody variable fragment (ScFv), the intracellular CD 3 zeta T cell receptor domain and the 4-1BB (cd137) costimulatory domain. Upon intravenous administration, the anti-mesothelin CIR mRNA-electroporated autologous T cells may attach to cancer cells expressing mesothelin. This may stimulate the secretion of multiple cytokines and may result in cell lysis of mesothelin-expressing cancer cells. Mesothelin is a cell surface glycoprotein involved in cell adhesion and is overexpressed in many epithelial-derived cancers.
A recombinant B7-DC Fc-fusion protein composed of the extracellular domain of the PD-1 ligand programmed cell death ligand 2 (PD-L2, B7-DC) and the Fc region of human immunoglobulin (Ig) G1, with potential immune checkpoint inhibitory and antineoplastic activities. Anti-PD-1 fusion protein AMP-224 specifically binds to PD-1 on chronically stimulated T-cells and reduces their proliferation. This may restore immune function and may result in the activation of cytotoxic T-cells and cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein of Ig superfamily and inhibitor receptor expressed on activated T-cells, negatively regulates T-cell activation and effector function when activated by its ligands, and plays an important role in tumor evasion from host immunity. AMP-224 does not bind normal activated T-cells.
A dual inhibitor of DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR), with potential antineoplastic activity. CC-115 binds to and inhibits the activity of DNA-PK and both raptor-mTOR (TOR complex 1 or TORC1) and rictor-mTOR (TOR complex 2 or TORC2), which may lead to a reduction in cellular proliferation of cancer cells expressing DNA-PK and TOR. DNA-PK, a serine/threonine kinase and a member of the PI3K-related kinase subfamily of protein kinases, is activated upon DNA damage and plays a key role in repairing double-stranded DNA breaks via the DNA nonhomologous end joining (NHEJ) pathway; mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, plays an important role downstream in the PI3K/Akt/mTOR signaling pathway.
A morphologic finding indicating the presence of basal cells in the epidermis with pale or clear-appearing cytoplasm.
Atrophy of the cerebral cortex and/or cerebellum due to chronic ethanol consumption.
Atrophy of the nervous system tissues and/or muscle tissues that is related to aging.
An adenosquamous carcinoma associated with the presence of human papillomavirus infection.
A grade I invasive lobular carcinoma of the breast, characterized by the presence of round groups of neoplastic cells.
A grade II invasive lobular carcinoma of the breast, characterized by the presence of neoplastic cells with large and atypical nuclei.
A grade I invasive lobular carcinoma of the breast, characterized by the presence of neoplastic cells that form trabeculae and groups infiltrating collagen bundles.
An invasive lobular carcinoma of the breast, characterized by the presence of neoplastic cells forming small tubular structures.
Condyloma acuminatum that is associated with the presence of dysplastic epithelial changes.
A congenital mesoblastic nephroma characterized by the presence of classic and cellular areas.
A cyst lined by tissue that resembles synovial villi.
A reactive, benign fibrous lesion that develops in the periosteum of the femur. It usually affects boys and there is a history of trauma. It is characterized by the formation of dense collagen tissue and reactive bone.
Extramedullary hematopoiesis occurring during adulthood.
An inherited disorder characterized by progressive degeneration and atrophy of the nervous system.
A rare, slow-growing, locally aggressive soft tissue tumor characterized by the presence of oval to spindle cells forming concentric aggregates around small vessels. Giant multinucleated cells are also present.
Hyperplasia of the bronchial epithelial cells. It is often associated with squamous metaplasia.
Hyperplasia of the germinal centers resulting in the enlargement of the lymph node.
An inborn metabolic disorder affecting the intermediary metabolism process. It results in accumulation of substances in the body that can cause acute or chronic intoxication.
A finding indicating the formation of calcium oxalate crystal deposits in an organ.
A finding indicating the presence of cadmium mineral deposits in an organ.
A morphologic finding indicating the presence of enlarged muscle cells in a muscle tissue sample.
A lesion in the prostate gland characterized by glandular atrophy, chronic inflammation, and epithelial hyperplasia. It has been suggested that it is a precancerous lesion and it may lead to the development of prostatic intraepithelial neoplasia and prostatic carcinoma.
A necrotizing vasculitis caused by Pseudomonas aeruginosa.
A vaccine containing detoxified tetanus toxoid, detoxified diphtheria toxoid and inactivated pertussis antigens.
A category of vaccines that use the extracted and purified outer polysaccharide coat of the particular bacteria.
A live attenuated bacteria injectable vaccine used to prevent typhoid, which is caused by Salmonella typhi.
Rejection of a transplanted organ that usually occurs after the first week of the transplantation. The risk of acute rejection is highest in the first three months following transplantation. Morphologically, there is an inflammatory infiltrate composed of lymphocytes and neutrophils and vascular damage in the rejected tissue.
A dinitroazetidine derivative with potential radiosensitizing activity. Upon administration, RRx-001 is able to dilate blood vessels, thereby increasing tumor blood flow and thus improving oxygenation to the tumor site. By increasing oxygen levels, these tumor cells may be more susceptible to radiation therapy. Tumor hypoxia is correlated with tumor aggressiveness, metastasis and resistance to radiotherapy.
A cell-based combination product consisting of a fibrinogen solution and a cell preparation containing allogeneic non-proliferating, living human skin-derived keratinocytes and fibroblasts, suspended in thrombin, with potential topical wound healing enhancing and topical anti-ulcer activity. Upon sequential spray of the two components of HP802-247 topically, a thin fibrin matrix is formed on the wound surface and the cellular components are capable of secreting wound healing cytokines and growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), granulocyte-macrophage colony-stimulating growth factor (GM-CSF) and keratinocyte growth factor. Cell concentration and keratinocyte-to-fibroblast ratio in HP802-247 are essential for optimal growth factor production and thus the efficacy of this agent.
A triazole containing pentapeptide labeled with the positron-emitting isotope fluorine F 18, used as a tracer for positron emitting tomography (PET) imaging. As a caspase-3 specific substrate, fluorine F 18 CP18 peptide is preferentially taken up by and accumulates in tumor cells with high caspase-3 activity. Upon PET imaging, apoptotic cells can be detected and apoptotic activity can be assessed. Caspase-3 is a cysteine protease that plays a key role in the induction of apoptosis.
A rare, benign, well-circumscribed salivary gland neoplasm that predominantly affects females. It is characterized by the presence of microcysts, ducts, and acini in a sclerotic stroma. Focal lymphocytic infiltrates may also be present.
A morphologic finding indicating the transformation of glandular or transitional epithelial cells to squamous epithelial cells that lack atypical features.
Karyotype with at least three chromosomal aberrations.
Scarring and atrophy of the renal cortex that occurs in hypertensive patients and in old age.
A molecular finding indicating that the immunoglobulin heavy chain variable region has an unmutated germline configuration.
An inherited disorder that presents with systemic manifestations.
A non-neoplastic disorder that affects the brain. Representative examples include cerebrovascular disorder, hydrocephalus, and encephalitis.
An orally bioavailable inhibitor of phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR kinase inhibitor DS-7423 inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in susceptible tumor cells. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K. Consequently, this agent may potentially be more potent than an agent that inhibits either PI3K kinase or mTOR kinase.
An electrolyte-free emulsion for infusion consisting of a three chamber bag system containing glucose, amino acids and lipids that can be used to provide parenteral nutritional supplementation. The lipid emulsion portion contains soybean oil, medium-chain triglycerides, olive oil and fish oil; the amino acid solution contains alanine, arginine, glycine, histidine, leucine, isoleucine, lysine, methionine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, and valine. The electrolyte-free parenteral nutrition emulsion contains no electrolytes, trace elements and vitamins. The three separate bags containing glucose, amino acids and lipids are mixed together before infusion.
A cancer vaccine consisting of allogeneic, immortalized dendritic precursor cells derived from a patient with acute myelogenous leukemia (AML), with potential immunostimulatory and antineoplastic activities. Upon ex vivo stimulation and expansion of the precursor cells into mature, fully functional dendritic cells (DCs) and subsequent administration, the allogeneic AML antigen-expressing DC vaccine may elicit a potent cytotoxic T-cell (CTL) and antibody response against AML antigen-expressing cells, resulting in tumor cell death.
The dihydrochloride salt form of quizartinib, an orally available small molecule with potential antineoplastic activity. Quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs), resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. Mutations in FLT3, resulting in constitutive activation, are the most frequent genetic alterations in acute myeloid leukemia (AML) and occur in approximately one-third of AML cases.
The dimaleate salt form of afatinib, an orally bioavailable anilino-quinazoline derivative and inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with antineoplastic activity. Upon administration, afatinib selectively and irreversibly binds to and inhibits the epidermal growth factor receptors 1 (ErbB1; EGFR), 2 (ErbB2; HER2), and 4 (ErbB4; HER4), and certain EGFR mutants, including those caused by EGFR exon 19 deletion mutations or exon 21 (L858R) mutations. This may result in the inhibition of tumor growth and angiogenesis in tumor cells overexpressing these RTKs. Additionally, afatinib inhibits the EGFR T790M gatekeeper mutation which is resistant to treatment with first-generation EGFR inhibitors. EGFR, HER2 and HER4 are RTKs that belong to the EGFR superfamily; they play major roles in both tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types.
A myelodysplastic syndrome characterized by the presence of a point mutation in one of the following genes, TP53, EZH2, ETV6, RUNX1, and ASXL1. These gene mutations are independent predictors of poor prognosis.
A molecular genetic abnormality that refers to the presence of a mutation in the histone methyltransferase gene EZH2.
A molecular genetic abnormality that refers to the presence of a mutation in the ETV6 gene (ETS variant gene 6).
A molecular genetic abnormality that refers to the presence of a mutation in the ASXL1 gene.
Donor tissue that is removed due to rejection.
A storage disorder that results from impaired metabolism of nickel.
An extended release, proprietary mucoadhesive buccal tablet formulation containing the hydrochloride salt form of clonidine, the imidazoline derivative and adrenergic alpha 2 receptor agonist, with anti-inflammatory activity. Upon contact of the tablet with the buccal mucosa, clonidine binds to the adrenergic receptors on macrophages and lymphocytes and may reduce the release of pro-inflammatory mediators such as tumor necrosis factor alpha (TNFalpha). As a result, this agent may prevent chemoradiation therapy-induced mucositis.
A third-generation epothilone B analogue with potential anti-mitotic and antineoplastic activites. Iso-fludelone binds to tubulin and induces microtubule polymerization and stabilizes microtubules against depolymerization, which may result in the inhibition of cell division, the induction of G2/M arrest, and apoptosis. Compared to other generations of epothilones, iso-fludelone exhibits increased stability, water solubility, potency, duration of action, tumor penetration as well as reduced toxicity. In addition, this agent is a not a substrate of the P-glycoprotein (P-gp), a multidrug resistance pump often overexpressed in cancer cells.
A radiotracer containing a pegylated dimeric Arg-Gly-Asp (RGD) peptide (NH2-mini-PEG-E[c(RGDyK)]2 or PRGD2) radiolabeled with fluorine 18F-fluorobenzoate (18F-FB), with potential alphaVbeta3 integrin imaging activity upon positron emission topography (PET). Upon administration, the RGD moiety of 18F-labeled Mini-PEG Spacered RGD Dimer (18F-FPRGD2) binds to alphaVbeta3 integrin. Upon PET, alphaVbeta3-expressing tumor cells can be visualized and the degree of tumor angiogenesis can be determined. This agent exhibits increased integrin receptor binding affinity, tumor cell uptake and increased radiolabeling yield as compared to the non-pegylated form (18F-FRGD2). Integrins, transmembrane glycoproteins, may be upregulated on proliferating tumor vessel endothelial cells and various cancer cells; their overexpression has been associated with neovascularization, differentiation, proliferation of tumor cells, metastasis and an overall poor prognosis.
A radiopharmaceutical agent comprised of a pegylated dimeric arginine-glycine-aspartic acid (RGD)-based peptide labeled with 2-fluoropropionyl, with potential alphaVbeta3 integrin imaging activity upon positron emission topography (PET). The RGD moiety of 2-fluoropropionyl-labeled pegylated dimeric RGD peptide targets and binds to alphaVbeta3 integrin. Upon PET imaging, alphaVbeta3 integrin-expressing tumor cells can be visualized and expression levels can be quantified. Compared to other fluorine F 18 labeled RGD-containing peptides, this agent shows increased affinity to alphaVbeta3 integrin, enhanced tumor uptake as well as improved pharmacokinetics. alphaVbeta3 integrin, overexpressed on certain tumor cells and tumor endothelial cells, plays a key role in angiogenesis, tumor proliferation and survival.
A humanized monoclonal antibody directed against the apoptotic ligand TNF-like weak inducer of apoptosis (TWEAK) with potential antineoplastic activity. Anti-TWEAK monoclonal antibody RO5458640 binds to TWEAK and prevents the binding of TWEAK to its receptor, FGF-inducible molecule 14 (Fn14), thereby blocking the TWEAK/Fn14 signaling. This may prevent tumor cell proliferation, invasion, migration and angiogenesis. TWEAK has pleiotropic effects, mediating proinflammatory and pro-angiogenic activity as well as stimulation of invasion, migration, and survival mediated via its receptor Fn14; Fn14 is expressed at relatively low levels in normal tissues, but is elevated in tumor cells and locally in injured and diseased tissues.
A combination peptide vaccine of 2 chimeric peptides of the promiscuous T cell epitope derived from measles virus fusion protein (MVF; amino acid residues 288-302) co-synthesized with B-cell epitopes derived from the HER-2/neu a.a. 597-626 and HER-2/neu a.a. 266-296, with potential antineoplastic activity. Vaccination with MVF-HER-2(597-626)/MVF-HER-2(266-296) peptide vaccine may be capable of inducing an active specific immune response, mounting a cytotoxic T-lymphocyte (CTL) response and an antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells that overexpress the HER-2 protein. The oncogenic protein HER-2, a member of the human epidermal growth factor receptor (EGFR) family of tyrosine kinases, is overexpressed in a variety of cancers and is correlated with increased tumor growth, progression and a poor prognosis. HER-2(597-626) corresponds to the binding site of trastuzumab on the extracellular domain IV of HER-2; HER-2 (266-296) corresponds to the binding site of pertuzumab on the dimerization loop of domain II of HER-2.
A radioimmunoconjugate containing the recombinant humanized monoclonal antibody trastuzumab conjugated with the bifunctional chelating agent TCMC ((1,4,7,10-Tetra-(2-Carbamoyl Methyl)-Cyclododecane), and radiolabeled with the alpha-emitting isotope lead Pb 212, with potential anti-tumor activity. Upon administration, the antibody moiety of lead Pb 212 TCMC-trastuzumab binds with high affinity to the extracellular domain of human epidermal growth factor receptor 2 (HER2); after internalization, the radioisotope moiety delivers a cytotoxic dose of alpha radiation to the HER2-expressing tumor cells. HER2, a tyrosine kinase receptor, is overexpressed on the cell surface of a variety of cancer cell types.
A proprietary recombinant protein highly resembling human interferon alpha 2b (IFN-a2b), with potential anti-tumor, anti-inflammatory, immunomodulating and antiviral activities. Upon injection, recombinant IFN alpha 2b-like protein binds to specific IFN alpha cell surface receptors. This activates interferon-mediated signal transduction pathways and induces the transcription and translation of genes with interferon-specific response elements (ISREs). This may activate the immune system, including the activation of natural killer cells (NKs) and may result in an inhibition of tumor cell proliferation, tumor angiogenesis, metastasis and an induction of apoptosis. Compared to human IFN-a2b (HuINF-a2b), this agent exhibits enhanced antiviral and antiproliferative activities. In addition, this agent exhibits antiviral activity against a variety of viruses, including hepatitis B and C viruses, human immunodeficiency virus (HIV) and Avian Influenza.
An orally available human chemokine receptor 2 (CCR2) antagonist with potential immunomodulating and antineoplastic activities. Upon oral administration, CCR2 antagonist PF-04136309 specifically binds to CCR2 and prevents binding of the endothelium-derived chemokine ligand CLL2 (monocyte chemoattractant protein-1 or MCP1) to its receptor CCR2, which may result in inhibition of CCR2 activation and signal transduction. This may inhibit inflammatory processes as well as angiogenesis, tumor cell migration, and tumor cell proliferation. The G-protein coupled receptor CCR2 is expressed on the surface of monocytes and macrophages, stimulates the migration and infiltration of these cell types, and plays an important role in inflammation, angiogenesis, and tumor cell migration and proliferation.
A preparation containing a mixture of multiple naturally occurring, active subtypes 1, 2, 8, 10, 14 and 21 of interferon alpha (IFN-alpha) with immunomodulating, anti-viral and anti-cancer activities. Multi-subtype natural human leukocyte IFN-alpha is purified from the leukocyte fraction of human blood challenged with Sendai virus. Upon administration, IFN-alpha subtypes bind to cell surface IFN-alpha receptors (IFNARs), resulting in an upregulation of interferon stimulated genes and related protein products. This ultimately leads to the proliferation of human B cells, activation of natural killer (NK) cells and dendritic cells (DCs), an increase in HLA-I and HLA-II expression and activation of CD8-lymphocytes. Compared to single-subtype IFN, multi-subtypes act synergistically.
An inhibitor of the proto-oncogene c-Met (also known as hepatocyte growth factor receptor (HGFR)) with potential antineoplastic activity. Upon intravenous administration, c-Met inhibitor SAR125844 binds to c-Met, thereby disrupting c-Met-mediated signal transduction pathways. This may result in cell growth inhibition in tumors that overexpress c-Met. c-Met, a receptor tyrosine kinase overexpressed or mutated in a variety of cancers, plays an important role in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis.
An orally bioavailable receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Famitinib binds to and inhibits several RTKs, dysregulated in a variety of tumors, including stem cell factor receptor (c-Kit; SCFR), vascular endothelial growth factor receptor (VEGFR) 2 and 3, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinases Flt1 and Flt3. Inhibition of these RTKs may result in an inhibition of tumor growth and angiogenesis, and eventually tumor regression in tumor cells overexpressing these RTKs.
A topical formulation containing the histone deacetylase (HDAC) inhibitor with potential antineoplastic activity. Upon cutaneous administration, SHP-141 selectively binds to and inhibits HDAC, resulting in an accumulation of highly acetylated histones in the skin (dermis and epidermis), the induction of chromatin remodeling, and the selective transcription of tumor suppressor genes. These events may result in the inhibition of tumor cell division and the induction of tumor cell apoptosis. HDACs, upregulated in many tumor cell types, are a family of metalloenzymes responsible for the deacetylation of chromatin histone proteins. Topical administration of SHP-141 allows for high concentrations of this agent locally while minimizing systemic toxicity.
A dietary supplement containing a green tea extract including the catechin epigallocatechin gallate and other vitamins and antioxidants, with potential antineoplastic and chemopreventive activities. The polyphenols in green tea act as antioxidants and scavenge free radicals which may inhibit cellular oxidation and prevent free radical damage to cells. In addition, polyphenols may affect enzymes involved in cellular reproduction and tumor angiogenesis by modulating angiogenic factors. Other ingredients in green tea extract-based antioxidant supplement include dry cinnamon extract, germanium, zinc sulfate, manganese sulfate, arginine, cysteine, malic acid, ascorbic acid (vitamin c), glycyrrhizinic acid, glycine, glucosamine, pyridoxal (vitamin B6), calcium pantothenate (vitamin B5), folic acid, cyanocobalamin (vitamin B12).
The sodium salt of leucovorin, an active metabolite of folic acid, used as an antidote to folic acid antagonists. Leucovorin does not require metabolism by dihydrofolate reductase, the molecular target of folate antagonists and counteracts the toxic effects of these drugs. This agent also potentiates the effects of fluorouracil and its derivatives by stabilizing the binding of the drug's metabolite to its target enzyme, thus prolonging drug activity. In comparison with the calcium salt, sodium salt does not form precipitate when mixed other folate antagonists.
A radioconjugate consisting of the 7 amino acid peptide sequence ASYNYDA (GI heptapeptide) and labeled with the fluorescent dye fluorescein isothiocyanate (5-FITC), with potential imaging activity. Upon topical application to the esophageal mucosa using a spray, the heptapeptide moiety of 5-FITC-labeled GI-heptapeptide binds to abnormal cells in the esophagus; the FITC moiety allows for imaging with white light and the area of interest for biopsies can then be visualized.
A preparation containing the inactivated Pseudomonas aeruginosa with potential immunomodulating activity. Upon inoculation, Pseudomonas aeruginosa preparation may stimulate the immune system, increasing macrophage and natural killer cell activity; it may be used thereby in cancer adjuvant treatments, and it may reduce the incidence of infection.
A small molecule and prodrug of CWP232204 targeting Src associated in mitosis, of 68 kDa (Sam68 or KHDRBS1), with potential antineoplastic activity. CWP232291 is converted in serum into its active form CWP232204 which binds to Sam68, thereby resulting in the induction of apoptosis in selective cancer cells. Due to the multimodular structure of Sam68, the apoptosis mediated by CWP232204-Sam68 interaction can attribute from 1) activation of transcription factor NF-kB induced by tumor necrosis factor alpha signaling, 2) alternative splicing of BCL-2 apoptosis gene, driving the balance towards pro-apoptotic as opposed to anti-apoptotic isoforms, 3) down-regulation of the anti-apoptotic protein survivin via Wnt signaling. Sam68, a KH domain RNA-binding protein belonging to the signal transduction and activation of RNA (STAR) family, plays a key role in various cellular processes including cell cycle progression and apoptosis; it is upregulated in many types of cancer cells and its expression is associated with increased cell proliferation and survival.
A cell-based cancer vaccine comprised of autologous dendritic cells (DCs) pulsed with cyclin B1 peptide, with potential immunostimulatory and antineoplastic activities. Upon administration, cyclin B1 peptide-pulsed autologous dendritic cell vaccine may stimulate anti-tumoral cytotoxic T lymphocyte (CTL) and anti-cyclin B1 antibody responses against cyclin B1-expressing cancer cells, resulting in tumor cell lysis. Cyclin B1, a key regulator of the cell cycle and cell division, is overexpressed in a variety of cancer cells.
A cell-based cancer vaccine comprised of brain tumor initiating cells (BTICs), with potential immunostimulating and antineoplastic activity. BITCs are from the glioblastoma multiforme (GBM) cell line GBM-6 and contain glioma stem-like cell-associated antigens. Upon administration, the BITC vaccine may stimulate a specific anti-tumoral cytotoxic T-lymphocyte (CTL) response against brain tumor cancer cells and brain tumor stem like cells, resulting in tumor cell lysis. BITC have unique antigenicity and have the ability to self-renew; vaccination against BITC antigens may kill these cells and may prevent tumor recurrences.
An oral rinse containing 1% of botanical extracts with potential anti-inflammatory and antimucositis activity. Upon rinsing with botanical extracts rinse IZN-6N4 in the oral cavity, this agent may prevent inflammation of the mucosal membranes and may decrease chemotherapy- and/or radiation-induced oral mucositis.
The mesylate salt form of PWT33597, an orally bioavailable dual inhibitor of phosphatidylinositide 3-kinase (PI3K) alpha and mammalian target of rapamycin (mTOR) kinase with potential antineoplastic activity. PI3K alpha/mTOR dual inhibitor PWT33597 selectively inhibits both PI3K alpha kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in PI3K/mTOR-overexpressing tumor cells. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K.
An antibody drug conjugate (ADC) containing a fully human monoclonal antibody AGS-22 targeting the cell adhesion molecule nectin-4 and conjugated, via a proprietary enzyme-cleavable linker, to the cytotoxic agent monomethyl auristatin E (MMAE) (AGS-22M6E), with potential antineoplastic activity. The monoclonal antibody moiety of AGS-22M6E selectively binds to nectin-4. After internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces apoptosis in nectin-4 overexpressing tumor cells. Nectin-4, a tumor associated antigen belonging to the nectin family, is overexpressed in a variety of cancers, including breast, bladder, lung and pancreatic cancer.
A glycoengineered form of a monoclonal antibody directed against the human epidermal growth factor receptor-2 (HER2), with potential antineoplastic activity. Glycooptimized trastuzumab-GEX specifically binds to the extracellular domain of HER2, thereby inducing an antibody-dependent cell-mediated cytotoxicity (ADCC) against HER2-expressing tumor cells. This eventually results in apoptosis and growth inhibition of tumor cells. HER2, a member of the receptor tyrosine kinase EGFR superfamily, is overexpressed on the cell surfaces of various solid tumors. This agent has a specific glycosylation profile that may enhance its ADCC response against HER2-expressing tumor cells.
A colloidal oatmeal-based skin cream with potential moisturizing and skin protecting activity. Upon application to the skin, colloidal oatmeal cream forms a protective barrier and thereby prevents water loss, provides moisture to the skin and protects the skin from damage.
A paste containing multiple skin protectants with anti-oxidant, skin protecting, moisturizing, anti-erythema and anti-inflammatory activities. The paste includes zinc oxide, aluminum starch octenylsuccinate, lanolin, allantoin, chamomile and sweet almond oil, rice bran oil, shea butter, dimethicone (polymerized siloxane), petrolatum, vitamin E, phytosome of glycyrrhetinic acid and botanical extracts derived from Calendula officinalis, Malva sylvestris and Tilia tomentosa. Upon application, this paste provides a physical barrier on the skin and may help protect, soothe and moisturize the skin as well as restore skin softness, integrity and elasticity. When this paste is applied to the perineum area, it may help prevent radiation-induced dermatitis.
A preparation containing L-menthol with potential anti-peristaltic activity. Upon spraying directly onto the gastric mucosa, L-menthol preparation NPO-11 may relax gastrointestinal smooth muscle. This may result in a suppression of gastric peristalsis and may be beneficial during upper GI endoscopic procedures.
A variation in or modification of the molecular sequence of a gene or gene product.
A variation in the amino acid sequence of a specific gene product.
A humanized monoclonal antibody directed against the cytokine interleukin-9 (IL-9), with potential immunomodulating activity. Upon administration, enokizumab binds to and blocks the activity of IL-9, thereby preventing IL-9-mediated effects. IL-9, a T-helper cell type 2-derived cytokine, is involved in airway inflammation and hyperrreactivity.
An active metabolite of MLN9708, a second generation, boron containing peptide proteasome inhibitor (PI) with potential antineoplastic activity. Ixazomib binds to and inhibits the 20S catalytic core of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome, which results in an accumulation of unwanted or misfolded proteins; disruption of various cell signaling pathways may follow, resulting in the induction of apoptosis. Compared to first generation PIs, second generation PIs may have an improved pharmacokinetic profile with increased potency and less toxicity. Proteasomes are large protease complexes that degrade unneeded or damaged proteins that have been ubiquinated.
A humanized monoclonal antibody (IgG2deltaA) raised against amyloid beta peptides with Alzheimer disease treatment application. Ponezumab recognizes and binds the free carboxy terminal amino acids 33-40 of the amyloid beta peptide 1-40 and may be used in a passive immunotherapy treatment.
A human IgG1, monoclonal antibody targeting GM-CSF, with immunomodulating activity. Namilumab binds to and neutralizes GM-CSF, by preventing GM-CSF from binding to its cell surface receptor, GM-CSFR. This leads to an inhibition of GM-CSF-mediated signaling and ultimately prevents inflammation. GM-CSF, a pro-inflammatory cytokine, stimulates the production of granulocytes and monocytes; it plays a key role in the activation of the innate immune system and in various autoimmune and inflammatory diseases.
A ruthenium-containing cancer agent targeting transferrin with potential antineoplastic activity. Upon intravenous administration, NKP-1339 (Ru3+) binds to transferrin (Tf) and is taken up via Tf receptors (TfR), which are overexpressed on cancer cells. Once inside the cell, NKP-1339 is released from Tf and is reduced, within the acidic environment of the endosomes, to its active form NKP-119 (Ru2+). In turn, the active form induces a redox reaction, thereby leading to the formation of reactive oxygen species (ROS) which inhibits GRP78 and SOD, endoplasmic reticulum-stress modulating molecules as well as BAG4 and ERK, program cell death regulating molecules. This eventually induces caspase-dependent apoptosis.
An orally available ATP-competitive inhibitor of the vascular endothelial growth factor receptor type 2 (VEGFR2), with potential anti-angiogenesis and antineoplastic activities. Upon administration, the VEGFR2 tyrosine kinase inhibitor PF-00337210 selectively binds to VEGFR2 and prevents its phosphorylation which may result in an inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and may eventually cause tumor cell death. VEGFR2, a receptor tyrosine kinase, is frequently overexpressed by a variety of tumor types.
A lipid depot-based therapeutic cancer vaccine composed of survivin epitopes, a universal T Helper peptide and a polynucleotide adjuvant encapsulated in liposomes and then formulated in the hydrophobic carrier Montanide ISA51 VG, with potential immunopotentiating and antineoplastic activities. Upon injection of the survivin antigen vaccine DPX-Survivac, a depot is created at the injection site from which the antigens and adjuvant are released. This vaccine may elicit a long lasting cellular response against survivin-expressing cancers, resulting in a decrease in tumor cell proliferation and an induction of tumor cell death. Survivin, a member of the inhibitor of apoptosis (IAP) family expressed during embryonic development, is upregulated in a variety of human cancers while absent in most normal adult cells; its expression in tumors is associated with a more aggressive phenotype, decreased survival, and increased resistance to chemotherapy.
A fully human monoclonal antibody directed against the cell surface glycoprotein CD-38 with potential antineoplastic activity. Anti-CD38 monoclonal antibody MOR03087 specifically binds to CD38 on CD38-positive tumor cells. This may trigger antitumoral antibody-dependent cellular cytotoxicity (ADCC) and may eventually lead to cell lysis in CD38-expressing tumor cells. CD38, a type II transmembrane glycoprotein, is present on various immune cells and hematologic malignancies, and its expression has been correlated with poor prognosis.
The hydrochloride salt form of rolapitant, an orally bioavailable, centrally-acting, selective, neurokinin 1 receptor (NK1-receptor) antagonist with potential antiemetic activity. Upon oral administration, rolapitant competitively binds to and blocks the activity of the NK1-receptor in the central nervous system, thereby inhibiting the binding of the endogenous ligand, substance P (SP). This may prevent both SP-induced emesis and chemotherapy-induced nausea and vomiting (CINV). The interaction of SP with the NK1-receptor plays a key role in the induction of nausea and vomiting caused by emetogenic cancer chemotherapy. Compared to other NK1-receptor antagonists, rolapitant has both a more rapid onset of action and a much longer half-life.
A replication incompetent adenovirus encoding the human pro-inflammatory cytokine interleukin-12 (IL-12) (INXN-2001) in combination with the proprietary activator ligand INXN-1001, with potential immunomodulating and antineoplastic activities. Production of IL-12 is controlled by an inducible DNA element that allows transcription initiation only in the presence of the ligand inducer. Upon intratumoral administration of INXN-2001 and oral administration of INXN-1001, INXN-1001 is able to induce expression of IL-12 from INXN-2001. IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma and inducing cytotoxic T cell responses against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation.
A fusion protein consisting of the heavy-chains of the human antibody NHS76, raised against DNA released by necrotic tumor cells, and fused to two molecules of a genetically modified human interleukin-12 (IL-12) with potential immunostimulating and antineoplastic activities. Upon administration, the antibody moiety of immunocytokine NHS-IL12 binds to DNA released from necrotic tumor cells located primarily at the core of necrotic solid tumors, thereby delivering the IL-12 moiety. In turn, the IL-12 moiety of this agent stimulates the host immune system to mount an immune response against tumor cells, thereby inhibiting tumor growth. IL-12 is a proinflammatory cytokine with numerous immunoregulatory functions and may augment host immune responses to tumor cells. By targeting tumor cells, NHS-IL-12 may reduce the toxicity associated with systemic administration of recombinant human IL-12.
A neuroendocrine carcinoma that arises from the breast. It is characterized by the presence of cellular solid nests and trabeculae that contain spindle-shaped, plasmacytoid, and large neuroendocrine cells.
Any inhibitor of the sodium-glucose co-transporter subtype 2 (SGLT2) with antihyperglycemic activity. By binding to and blocking SGLT2, these inhibitors suppress reabsorption of glucose in the proximal tubule within the kidneys and thereby enhancing urinary excretion of glucose. This eventually normalizes blood glucose levels. SGLT2, a transport system exclusively expressed in the proximal renal tubules, mediates about 90% of renal glucose reabsorption from tubular fluid.
An orally available, dietary supplement consisting of lyophilized blueberry powder, with antioxidant and potential chemopreventive and chemosensitizing activity. In addition to vitamins and minerals, blueberries are rich in phytonutrients, such as proanthocyanidins, anthocyanins (e.g. malvidin, delphinidin, pelargonidin, cyanidin, petunidin, and peonidin), hydroxycinnamic acids, hydroxybenzoic acids, pterostilbene, resveratrol, and flavonols (e.g. kaempferol, quercetin and myricetin). Although the exact mechanism of action through which blueberries may exert their anti-tumor effect has yet to be fully elucidated, the effects of blueberry powder on cancer cells may be attributable to the phytonutrient's antioxidant and pro-apoptotic activities.
An orally bioavailable, small molecule inhibitor of Janus-associated kinase 2 (JAK2) and Src-family kinases, with potential antineoplastic activity. JAK2 inhibitor NS-018 competes with ATP for binding to JAK2 as well as the mutated form JAK2V617F, thereby inhibiting the activation of JAK2 and downstream molecules in the JAK2/STAT3 (signal transducer and activator of transcription 3) signaling pathway that plays an important role in normal development, particularly hematopoiesis. In addition, NS-018 inhibits the Src family tyrosine kinases. This eventually leads to the induction of tumor cell apoptosis. JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders (MPDs); JAK2V617F is a constitutively activated kinase that activates the JAK/STAT signaling pathway and dysregulates cell growth and function, and its expression transforms hematopoietic cells to cytokine-independent growth.
A radiologic finding that is seen in osteopetrosis. It is characterized by an increased sclerosis in the superior and inferior aspects of the midbody of the vertebra, resulting in the image of a duplicate vertebral body inside the normal one.
A radiologic finding that is detected with frontal chest X-ray or chest CT scan. It is characterized by bilateral perihilar pulmonary shadowing. It is seen in pulmonary edema, pulmonary hemorrhage, pneumonia, carcinoma, and lymphoid malignancies.
A benign or malignant pathologic structure in any part of the body, resulting from a neoplastic accumulation of cells.
A suspension of nanoparticles containing inert inorganic hafnium oxide (HfO2) crystals with potential antineoplastic activity. Upon injection of NBTXR3 in the tumor, the hafnium oxide-containing nanoparticles accumulate into the tumor cells. Subsequent application of radiation beams to the tumor tissue causes HfO2 particles to emit huge amounts of electrons. This results in the formation of free radicals within the tumor cells, which in turn causes targeted destruction of the cancer cells. Compared to standard radiotherapy, because of the inert nature of NBTXR3, this agent emits electrons only during its exposure to radiation which improves radiotherapy efficiency.
A cancer cell vaccine comprised of the allogeneic human lung adenocarcinoma cell line H1944 that has been transduced ex vivo with adenoviral vector encoding human cytokine chemokine C-C motif ligand 21 (CCL21), with potential immunomodulating and antineoplastic activities. Upon administration, CCL21-expressing H1944 cell vaccine expresses the chemokine CCL21, which may induce an antitumoral cytotoxic T-lymphocyte immune response in the tumor microenvironment. CCL21 has been shown to attract antigen presenting cells (APCs), like leukocytes and DCs, and natural killer (NK) cells and their T-cell effectors to induce a cytotoxic immune response. H1944 cells contain tumor-associated antigens (TAAs) overexpressed in non-small cell lung cancer (NSCLC).
An allogeneic cancer vaccine composed of lethally irradiated whole melanoma cancer cells that are genetically modified to secrete the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Upon intradermal injections, allogeneic GM-CSF-secreting lethally irradiated whole melanoma cell vaccine secretes GM-CSF. In turn, GM-CSF may stimulate the body's immune system against tumor cells by enhancing the activation of dendritic cells (DCs) and promoting antigen presentation to both B- and T-lymphocytes. In addition, GM-CSF promotes antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function.
A recombinant, oncolytic serotype 5/3 capsid-modified adenovirus encoding the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) with potential antineoplastic activity. Upon administration, the oncolytic adenovirus selectively infects and replicates in tumor cells, which may result in tumor cell lysis. Synergistically, GM-CSF (sargramostim) expressed by the oncolytic adenovirus enhances antigen presentation, promotes natural killer (NK) cell-mediated killing and causes a cytotoxic T cell (CTL) response against tumor cells harboring the oncolytic adenovirus, resulting in an immune-mediated tumor cell death. CGTG-102 is designed to replicate only in cells with defects in the p16/Rb/E2F pathway, attributed to a mutation common in many solid tumors. Replacement of the Ad5 capsid protein knob with a knob domain from serotype 3 causes higher transduction in cancer cells as compared to normal cells.
A colloidal mixture of nanoparticles consisting of small interfering RNA (siRNA) targeting the native eukaryotic translation initiation factor 5A (eIF5A), plasmids expressing a pro-apoptotic mutant of elF5A under the control of a B-cell specific promoter (B29), and a synthetic cationic polymer polyethylenimine (PEI) as a delivery vehicle, with potential antineoplastic activity. Upon administration, the siRNA component of SNS01-T suppresses elF5A expression, thereby interfering with translation of eIF5A and reducing levels of hypusinated elF5A in cancer cells. In turn, this inhibits activation of the transcription factor NF-kB and induces apoptosis. In addition, the B-cell specific plasmid component expresses an arginine substituted form of eIF5A, eIF5AK50R, which can not be hypusinated, thus leads to a selective induction of apoptosis in B-cells. The native unhypusinated form of eIF5A is pro-apoptotic and can be modified at the lysine residue, by deoxyhypusine synthase (DHS) and subsequently deoxyhypusine hydroxylase (DHH), to the anti-apoptotic hypusinated form which is associated with tumor cell growth and survival. The delivery vehicle protects the siRNA and plasmid from degradation.
An orally available, vitamin E derivative and androgen receptor (AR) antagonist with potential anti-oxidant, chemopreventative and antineoplastic activity. APC-100 binds to ARs in target tissues thereby inhibiting androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus. By inhibiting the formation of the complex between androgen activated AR- and the AP1 transcription factor JunD, the expression of androgen-responsive genes are blocked. One of such gene is spermidine/spermine N1-acetyl transferase gene (SSAT) that is responsible for the breakdown of polyamines, which are produced in high levels by prostatic epithelial cells, into reactive oxygen species (ROS) that cause cellular damage. APC-100 may ultimately lead to an inhibition of growth in both AR-dependent and AR-independent prostate tumor cells.
A teratoma that arises from the testis or ovary.
A recombinant form of a human macrophage inflammatory protein-1 alpha (MIP1-alpha) with a substitution of aspartate to alanine at position 26, with potential immunomodulating and radiotherapy potentiating activity. Intravenous administration of recombinant MIP1-alpha variant ECI301 after local tumor irradiation enhances the anti-tumor effect of ionizing radiation at the irradiated site as well as the antitumor effect at non-irradiated tumor sites (known as the abscopal effect). The abscopal effect appears to be attributed to this agent's ability to recruit and activate leukocytes, such as monocytes, dendritic cells, natural killer cells and T lymphocytes, thereby initiating an anti-tumor immune response against cancer cells. MIP1-alpha, also known as chemokine (C-C motif) ligand 3, is a ligand for the chemokine receptors CCR1, CCR4 and CCR5 that are involved in immune and inflammatory responses.
A fully human IgG2 monoclonal antibody against the colony-stimulating factor-1 (CSF-1 or M-CSF) receptor c-fms (or CSFR1), with potential antineoplastic activity. Upon administration, anti-c-fms monoclonal antibody AMG 820 binds to and blocks c-fms, thereby blocking CSF-1 binding to its receptor and suppressing CSF-1-induced c-fms signaling. This results in the suppression of recruitment and activation of tumor associated macrophages (TAM) within the tumor microenvironment. This eventually leads to a decrease in tumor growth. c-fms, a transmembrane protein belonging to the tyrosine kinase family, is overexpressed in certain tumor cell types and plays an essential role in macrophage differentiation and regulation of cell proliferation. The presence of TAM is correlated with tumor proliferation, invasion and a poor prognosis.
A humanized monoclonal antibody targeting glycolipids, with potential immunomodulating and antineoplastic activity. Upon administration, monoclonal antibody CEP-37250/KHK2804 targets and binds to a specific tumor antigen, thereby stimulating the immune system to exert an antibody-dependent cellular cytotoxicity (ADCC) against the tumor associated antigen (TAA)-expressing cancer cells. This agent has shown to be active in both wild-type and mutant K-RAS-expressing colorectal cancer cells.
A radiologic finding observed during magnetic resonance imaging of brain glioblastoma, following concurrent radiotherapy and temozolomide treatment or vaccine therapy. It refers to the false positive finding of progression and enhancement of the lesion. It is considered a treatment effect due to tumor cell necrosis and subsequent edema formation and increased vascular permeability.
A variation in the amino acid sequence for the RAC-alpha serine/threonine-protein kinase protein.
A change in the nucleotide sequence of the AKT1 gene.
A nucleotide substitution at position 49 of the coding sequence of the AKT1 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 17 in the RAC-alpha serine/threonine-protein kinase protein where glutamic acid has been replaced by lysine.
A variation in the amino acid sequence for the serine/threonine-protein kinase B-raf protein.
A change in the amino acid residue at position 466 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by alanine.
A nucleotide substitution at position 1397 of the coding sequence of the BRAF gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 466 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by glutamic acid.
A nucleotide substitution at position 1397 of the coding sequence of the BRAF gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 466 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by arginine.
A nucleotide substitution at position 1396 of the coding sequence of the BRAF gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 466 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by valine.
A nucleotide substitution at position 1397 of the coding sequence of the BRAF gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 469 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by alanine.
A nucleotide substitution at position 1406 of the coding sequence of the BRAF gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 469 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by glutamic acid.
A nucleotide substitution at position 1406 of the coding sequence of the BRAF gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 469 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by arginine.
A nucleotide substitution at position 1405 of the coding sequence of the BRAF gene where guanine has been mutated to cytosine.
A nucleotide substitution at position 1405 of the coding sequence of the BRAF gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 469 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by serine.
A complex substitution where the nucleotide sequence at positions 1405 and 1406 of the coding sequence of the BRAF gene has changed from guanine-guanine to thymine-cytosine.
A complex substitution where the nucleotide sequence at positions 1405 through 1407 of the coding sequence of the BRAF gene has changed from guanine-guanine-adenine to adenine-guanine-cytosine.
A complex substitution where the nucleotide sequence at positions 1405 through 1407 of the coding sequence of the BRAF gene has changed from guanine-guanine-adenine to adenine-guanine-thymine.
A change in the amino acid residue at position 469 in the serine/threonine protein kinase B-raf protein where glycine has been replaced by valine.
A nucleotide substitution at position 1406 of the coding sequence of the BRAF gene where guanine has been mutated to thymine.
A nucleotide substitution at position 1791 of the coding sequence of the BRAF gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 597 in the serine/threonine protein kinase B-raf protein where leucine has been replaced by glutamine.
A nucleotide substitution at position 1790 of the coding sequence of the BRAF gene where thymine has been mutated to adenine.
A change in the amino acid residue at position 597 in the serine/threonine protein kinase B-raf protein where leucine has been replaced by arginine.
A nucleotide substitution at position 1790 of the coding sequence of the BRAF gene where thymine has been mutated to guanine.
A change in the amino acid residue at position 597 in the serine/threonine protein kinase B-raf protein where leucine has been replaced by serine.
A complex substitution where the nucleotide sequence at positions 1789 and 1790 of the coding sequence of the BRAF gene has changed from cytosine-thymine to thymine-cytosine.
A change in the amino acid residue at position 597 in the serine/threonine protein kinase B-raf protein where leucine has been replaced by valine.
A nucleotide substitution at position 1789 of the coding sequence of the BRAF gene where cytosine has been mutated to guanine.
A change in the amino acid residue at position 600 in the serine/threonine protein kinase B-raf protein where valine has been replaced by alanine.
A nucleotide substitution at position 1799 of the coding sequence of the BRAF gene where thymine has been mutated to cytosine.
A change in the amino acid residue at position 600 in the serine/threonine protein kinase B-raf protein where valine has been replaced by aspartic acid.
A complex substitution where the nucleotide sequence at positions 1799 and 1780 of the coding sequence of the BRAF gene has changed from thymine-guanine to adenine-thymine.
A change in the amino acid residue at position 600 in the serine/threonine protein kinase B-raf protein where valine has been replaced by glutamic acid.
A complex substitution where the nucleotide sequence at positions 1799 and 1780 of the coding sequence of the BRAF gene has changed from thymine-guanine to adenine-adenine.
A nucleotide substitution at position 1799 of the coding sequence of the BRAF gene where thymine has been mutated to adenine.
A change in the amino acid residue at position 600 in the serine/threonine protein kinase B-raf protein where valine has been replaced by glycine.
A nucleotide substitution at position 1799 of the coding sequence of the BRAF gene where thymine has been mutated to guanine.
A change in the amino acid residue at position 600 in the serine/threonine protein kinase B-raf protein where valine has been replaced by lysine.
A complex substitution where the nucleotide sequence at positions 1798 and 1799 of the coding sequence of the BRAF gene has changed from guanine-thymine to adenine-adenine.
A change in the amino acid residue at position 600 in the serine/threonine protein kinase B-raf protein where valine has been replaced by leucine.
A nucleotide substitution at position 1798 of the coding sequence of the BRAF gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 600 in the serine/threonine protein kinase B-raf protein where valine has been replaced by methionine.
A nucleotide substitution at position 1798 of the coding sequence of the BRAF gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 600 in the serine/threonine protein kinase B-raf protein where valine has been replaced by arginine.
A complex substitution where the nucleotide sequence at positions 1798 and 1799 of the coding sequence of the BRAF gene has changed from guanine-thymine to adenine-guanine.
A complex substitution where the nucleotide sequence at positions 1797 through 1799 of the coding sequence of the BRAF gene has changed from adenine-guanine-thymine to guanine-adenine-guanine.
A variation in the amino acid sequence for the epidermal growth factor receptor protein.
A variation in the amino acid sequence for the receptor tyrosine-protein kinase erbB-2 protein.
An insertion of the amino acid sequence tyrosine-valine-methionine-alanine between the alanine at position 775 and the glycine at position 776 of the epidermal growth factor receptor protein.
An insertion of 12 nucleotides, TACGTGATGGCT, between position 2325 and 2326 of the coding sequence of the ERBB2 gene.
An insertion of 12 nucleotides, ATACGTGATGGC, between position 2324 and 2325 of the coding sequence of the ERBB2 gene.
A variation in the amino acid sequence for the GTPase KRas protein.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by alanine.
A nucleotide substitution at position 35 of the coding sequence of the KRAS gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by cysteine.
A nucleotide substitution at position 34 of the coding sequence of the KRAS gene where guanine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 34 through 36 of the coding sequence of the KRAS gene has changed from guanine-guanine-thymine to thymine-guanine-cytosine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by aspartic acid.
A nucleotide substitution at position 35 of the coding sequence of the KRAS gene where guanine has been mutated to adenine.
A complex substitution where the nucleotide sequence at positions 35 through 36 of the coding sequence of the KRAS gene has changed from guanine-thymine to adenine-cytosine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by glutamic acid.
A complex substitution where the nucleotide sequence at positions 35 through 36 of the coding sequence of the KRAS gene has changed from guanine-thymine to adenine-guanine.
A complex substitution where the nucleotide sequence at positions 35 through 36 of the coding sequence of the KRAS gene has changed from guanine-thymine to adenine-adenine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by phenylalanine.
A complex substitution where the nucleotide sequence at positions 34 through 35 of the coding sequence of the KRAS gene has changed from guanine-guanine to thymine-thymine.
A nucleotide substitution at position 36 of the coding sequence of the KRAS gene where thymine has been mutated to cytosine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by isoleucine.
A complex substitution where the nucleotide sequence at positions 34 through 35 of the coding sequence of the KRAS gene has changed from guanine-guanine to adenine-thymine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by leucine.
A complex substitution where the nucleotide sequence at positions 34 through 35 of the coding sequence of the KRAS gene has changed from guanine-guanine to cytosine-thymine.
A morphologic finding that refers to the accumulation of glial cells encircling neurons in a tissue specimen.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by asparagine.
A morphologic finding that refers to the accumulation of glial cells encircling vessels in a tissue specimen.
A complex substitution where the nucleotide sequence at positions 34 through 35 of the coding sequence of the KRAS gene has changed from guanine-guanine to adenine-adenine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by arginine.
A nucleotide substitution at position 34 of the coding sequence of the KRAS gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by serine.
A nucleotide substitution at position 34 of the coding sequence of the KRAS gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by valine.
A nucleotide substitution at position 35 of the coding sequence of the KRAS gene where guanine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 35 through 36 of the coding sequence of the KRAS gene has changed from guanine-thymine to thymine-cytosine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by tryptophan.
A complex substitution where the nucleotide sequence at positions 34 through 36 of the coding sequence of the KRAS gene has changed from guanine-guanine-thymine to thymine-guanine-guanine.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by tyrosine.
A complex substitution where the nucleotide sequence at positions 34 through 35 of the coding sequence of the KRAS gene has changed from guanine-guanine to thymine-adenine.
An oral capsule containing a proprietary formulation of the organoselenium compound ebselen, with potential anti-oxidant, anti-inflammatory and cytoprotective activity. Upon oral administration of SPI-1005, this agent mimics the activity of glutathione peroxidase (GPx) and can utilize glutathione to reduce other unstable molecules, thus preventing the formation of reactive oxygen species (ROS) and reducing oxidative stress on the cell. In the cochlea, this agent may prevent drug-induced injury to the auditory hair cells thereby preventing hearing loss. GPx is the main antioxidant enzyme in the cochlea and protects the inner ear from loud sounds and biochemical damage. In addition, ebselen is able to inhibit the activity of many enzymes involved in inflammation.
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by alanine.
A nucleotide substitution at position 38 of the coding sequence of the KRAS gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by cysteine.
A nucleotide substitution at position 37 of the coding sequence of the KRAS gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by aspartic acid.
A nucleotide substitution at position 38 of the coding sequence of the KRAS gene where guanine has been mutated to adenine.
A complex substitution where the nucleotide sequence at positions 38 through 39 of the coding sequence of the KRAS gene has changed from guanine-cytosine to adenine-thymine.
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by glutamic acid.
A complex substitution where the nucleotide sequence at positions 38 through 39 of the coding sequence of the KRAS gene has changed from guanine-cytosine to adenine-guanine.
A complex substitution where the nucleotide sequence at positions 38 through 39 of the coding sequence of the KRAS gene has changed from guanine-cytosine to adenine-adenine.
A nucleotide substitution at position 39 of the coding sequence of the KRAS gene where cytosine has been mutated to thymine.
A nucleotide substitution at position 39 of the coding sequence of the KRAS gene where cytosine has been mutated to guanine.
A nucleotide substitution at position 39 of the coding sequence of the KRAS gene where cytosine has been mutated to adenine.
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by asparagine.
A complex substitution where the nucleotide sequence at positions 37 through 38 of the coding sequence of the KRAS gene has changed from guanine-guanine to adenine-adenine.
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by arginine.
A nucleotide substitution at position 37 of the coding sequence of the KRAS gene where guanine has been mutated to cytosine.
A complex substitution where the nucleotide sequence at positions 37 through 39 of the coding sequence of the KRAS gene has changed from guanine-guanine-cytosine to cytosine-guanine-thymine
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by serine.
A nucleotide substitution at position 37 of the coding sequence of the KRAS gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by valine.
A nucleotide substitution at position 38 of the coding sequence of the KRAS gene where guanine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 38 through 39 of the coding sequence of the KRAS gene has changed from guanine-cytosine to thymine-thymine.
A complex substitution where the nucleotide sequence at positions 38 through 39 of the coding sequence of the KRAS gene has changed from guanine-cytosine to thymine-guanine.
A change in the amino acid residue at position 61 in the GTPase KRas protein where glutamine has been replaced by aspartic acid.
A change in the amino acid residue at position 61 in the GTPase KRas protein where glutamine has been replaced by glutamic acid.
A nucleotide substitution at position 181 of the coding sequence of the KRAS gene where cytosine has been mutated to guanine.
A change in the amino acid residue at position 61 in the GTPase KRas protein where glutamine has been replaced by histidine.
A nucleotide substitution at position 183 of the coding sequence of the KRAS gene where adenine has been mutated to thymine.
A nucleotide substitution at position 183 of the coding sequence of the KRAS gene where adenine has been mutated to cytosine.
A change in the amino acid residue at position 61 in the GTPase KRas protein where glutamine has been replaced by lysine.
A nucleotide substitution at position 181 of the coding sequence of the KRAS gene where cytosine has been mutated to adenine.
A complex substitution where the nucleotide sequence at positions 180 through 181 of the coding sequence of the KRAS gene has changed from thymine-cytosine to adenine-adenine.
A complex substitution where the nucleotide sequence at positions 180 through 181 of the coding sequence of the KRAS gene has changed from thymine-cytosine to cytosine-adenine.
A change in the amino acid residue at position 61 in the GTPase KRas protein where glutamine has been replaced by leucine.
A nucleotide substitution at position 182 of the coding sequence of the KRAS gene where adenine has been mutated to thymine.
A change in the amino acid residue at position 61 in the GTPase KRas protein where glutamine has been replaced by proline.
A nucleotide substitution at position 182 of the coding sequence of the KRAS gene where adenine has been mutated to cytosine.
A change in the amino acid residue at position 61 in the GTPase KRas protein where glutamine has been replaced by arginine.
A nucleotide substitution at position 182 of the coding sequence of the KRAS gene where adenine has been mutated to guanine.
A variation in the amino acid sequence for the GTPase NRas protein.
A change in the amino acid residue at position 61 in the GTPase NRas protein where glutamine has been replaced by glutamic acid.
A nucleotide substitution at position 181 of the coding sequence of the NRAS gene where cytosine has been mutated to guanine.
A change in the amino acid residue at position 61 in the GTPase NRas protein where glutamine has been replaced by histidine.
A nucleotide substitution at position 183 of the coding sequence of the NRAS gene where adenine has been mutated to cytosine.
A nucleotide substitution at position 183 of the coding sequence of the NRAS gene where adenine has been mutated to thymine.
A change in the amino acid residue at position 61 in the GTPase NRas protein where glutamine has been replaced by lysine.
A nucleotide substitution at position 181 of the coding sequence of the NRAS gene where cytosine has been mutated to adenine.
A complex substitution where the nucleotide sequence at positions 180 through 181 of the coding sequence of the NRAS gene has changed from adenine-cytosine to thymine-adenine.
A complex substitution where the nucleotide sequence at positions 181 through 183 of the coding sequence of the NRAS gene has changed from cytosine-adenine-adenine to adenine-adenine-guanine.
A change in the amino acid residue at position 61 in the GTPase NRas protein where glutamine has been replaced by leucine.
A nucleotide substitution at position 182 of the coding sequence of the NRAS gene where adenine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 181 through 182 of the coding sequence of the NRAS gene has changed from cytosine-adenine to thymine-thymine.
A complex substitution where the nucleotide sequence at positions 182 through 183 of the coding sequence of the NRAS gene has changed from adenine-adenine to thymine-guanine.
A change in the amino acid residue at position 61 in the GTPase NRas protein where glutamine has been replaced by proline.
A nucleotide substitution at position 182 of the coding sequence of the NRAS gene where adenine has been mutated to cytosine.
A nucleotide substitution at position 183 of the coding sequence of the NRAS gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 61 in the GTPase NRas protein where glutamine has been replaced by arginine.
A nucleotide substitution at position 182 of the coding sequence of the NRAS gene where adenine has been mutated to guanine.
A complex substitution where the nucleotide sequence at positions 181 through 182 of the coding sequence of the NRAS gene has changed from cytosine-adenine to adenine-guanine.
A complex substitution where the nucleotide sequence at positions 182 through 183 of the coding sequence of the NRAS gene has changed from adenine-adenine to guanine-guanine.
A variation in the amino acid sequence for the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein.
A change in the amino acid residue at position 545 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by alanine.
A nucleotide substitution at position 1634 of the coding sequence of the PIK3CA gene where adenine has been mutated to cytosine.
A change in the amino acid residue at position 545 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by aspartic acid.
A nucleotide substitution at position 1635 of the coding sequence of the PIK3CA gene where guanine has been mutated to thymine.
A nucleotide substitution at position 1635 of the coding sequence of the PIK3CA gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 545 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by glycine.
A nucleotide substitution at position 1634 of the coding sequence of the PIK3CA gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 545 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by lysine.
A nucleotide substitution at position 1633 of the coding sequence of the PIK3CA gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 545 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by glutamine.
A nucleotide substitution at position 1633 of the coding sequence of the PIK3CA gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 545 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by valine.
A nucleotide substitution at position 1634 of the coding sequence of the PIK3CA gene where adenine has been mutated to thymine.
A change in the amino acid residue at position 542 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by lysine.
A nucleotide substitution at position 1624 of the coding sequence of the PIK3CA gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 542 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by glutamine.
A nucleotide substitution at position 1624 of the coding sequence of the PIK3CA gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 542 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by valine.
A nucleotide substitution at position 1625 of the coding sequence of the PIK3CA gene where adenine has been mutated to thymine.
A change in the amino acid residue at position 1047 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where histidine has been replaced by leucine.
A nucleotide substitution at position 3140 of the coding sequence of the PIK3CA gene where adenine has been mutated to thymine.
A change in the amino acid residue at position 1047 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where histidine has been replaced by glutamine.
A nucleotide substitution at position 3141 of the coding sequence of the PIK3CA gene where thymine has been mutated to guanine.
A change in the amino acid residue at position 1047 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where histidine has been replaced by arginine.
A nucleotide substitution at position 3140 of the coding sequence of the PIK3CA gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 1047 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where histidine has been replaced by threonine.
A change in the amino acid residue at position 1047 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where histidine has been replaced by tyrosine.
A well differentiated neuroendocrine tumor that arises from the stomach. It produces serotonin and it may occasionally be found in association with a carcinoid syndrome.
A neuroendocrine tumor arising from the wall of the appendix, producing glucagon-like peptides. Morphologically, it is characterized by the presence of neoplastic cells forming tubular or trabecular patterns.
A neuroendocrine tumor that arises from the colon and produces glucagon-like peptides. Morphologically, it is characterized by the presence of neoplastic cells forming tubular or trabecular patterns.
A neuroendocrine tumor that arises from the gastrointestinal tract and produces glucagon-like peptides. Morphologically, it is characterized by the presence of neoplastic cells forming tubular or trabecular patterns.
A gastrin-producing neuroendocrine tumor that arises from the small intestine. It is characterized by the presence of uniform cells that form pseudorosettes. The neoplastic cells have uniform nuclei and small amount of eosinophilic cytoplasm.
A well differentiated neuroendocrine tumor that arises from the small intestine and produces serotonin.
A neuroendocrine tumor that arises from the small intestine and produces glucagon-like peptides. Morphologically, it is characterized by the presence of neoplastic cells forming tubular or trabecular patterns.
A nucleotide substitution at position 3139 of the coding sequence of the PIK3CA gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 420 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where cysteine has been replaced by arginine.
A nucleotide substitution at position 1258 of the coding sequence of the PIK3CA gene where thymine has been mutated to cytosine.
A change in the amino acid residue at position 542 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by glycine.
A nucleotide substitution at position 1625 of the coding sequence of the PIK3CA gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 861 in the epidermal growth factor receptor protein where leucine has been replaced by phenylalanine.
A change in the amino acid residue at position 861 in the epidermal growth factor receptor protein where leucine has been replaced by proline.
A change in the amino acid residue at position 861 in the epidermal growth factor receptor protein where leucine has been replaced by glutamine.
A nucleotide substitution at position 2582 of the coding sequence of the EGFR gene where thymine has been mutated to adenine.
A change in the amino acid residue at position 861 in the epidermal growth factor receptor protein where leucine has been replaced by arginine.
A nucleotide substitution at position 2582 of the coding sequence of the EGFR gene where thymine has been mutated to guanine.
A change in the amino acid residue at position 861 in the epidermal growth factor receptor protein where leucine has been replaced by valine.
A nucleotide substitution at position 2581 of the coding sequence of the EGFR gene where cytosine has been mutated to guanine.
A change in the amino acid residue at position 790 in the epidermal growth factor receptor protein where threonine has been replaced by methionine.
A nucleotide substitution at position 2369 of the coding sequence of the EGFR gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 858 in the epidermal growth factor receptor protein where leucine has been replaced by alanine.
A change in the amino acid residue at position 858 in the epidermal growth factor receptor protein where leucine has been replaced by glycine.
A change in the amino acid residue at position 858 in the epidermal growth factor receptor protein where leucine has been replaced by lysine.
A complex substitution where the nucleotide sequence at positions 2572 and 2573 of the coding sequence of the EGFR gene has changed from cytosine-thymine to adenine-adenine.
A nucleotide substitution at position 2572 of the coding sequence of the EGFR gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 858 in the epidermal growth factor receptor protein where leucine has been replaced by methionine.
A nucleotide substitution at position 2572 of the coding sequence of the EGFR gene where cytosine has been mutated to adenine.
A change in the amino acid residue at position 858 in the epidermal growth factor receptor protein where leucine has been replaced by proline.
A change in the amino acid residue at position 858 in the epidermal growth factor receptor protein where leucine has been replaced by glutamine.
A nucleotide substitution at position 2573 of the coding sequence of the EGFR gene where thymine has been mutated to adenine.
A change in the amino acid residue at position 858 in the epidermal growth factor receptor protein where leucine has been replaced by arginine.
A nucleotide substitution at position 2573 of the coding sequence of the EGFR gene where thymine has been mutated to guanine.
A complex substitution where the nucleotide sequence at positions 2573 and 2574 of the coding sequence of the EGFR gene has changed from thymine-guanine to guanine-thymine.
A complex substitution where the nucleotide sequence at positions 2572 and 2573 of the coding sequence of the EGFR gene has changed from cytosine-thymine to adenine-guanine.
A change in the amino acid residue at position 858 in the epidermal growth factor receptor protein where leucine has been replaced by tryptophan.
A change in the amino acid residue at position 719 in the epidermal growth factor receptor protein where glycine has been replaced by alanine.
A nucleotide substitution at position 2156 of the coding sequence of the EGFR gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 719 in the epidermal growth factor receptor protein where glycine has been replaced by cysteine.
A nucleotide substitution at position 2155 of the coding sequence of the EGFR gene where guanine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 2154 and 2155 of the coding sequence of the EGFR gene has changed from guanine-guanine to thymine-thymine.
A change in the amino acid residue at position 719 in the epidermal growth factor receptor protein where glycine has been replaced by aspartic acid.
A nucleotide substitution at position 2156 of the coding sequence of the EGFR gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 719 in the epidermal growth factor receptor protein where glycine has been replaced by serine.
A nucleotide substitution at position 2155 of the coding sequence of the EGFR gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 719 in the epidermal growth factor receptor protein where glycine has been replaced by valine.
A change in the amino acid composition of the epidermal growth factor receptor protein where a frame shift mutation results in the placement of a stop codon just after the glutamic acid residue at position 709.
A change in the amino acid composition of the epidermal growth factor receptor protein where a frameshift mutation results in the placement of a stop codon just after the glutamic acid residue at position 709.
A change in the amino acid composition of the epidermal growth factor receptor protein where a frameshift mutation results in the insertion of 28 non-canonic amino acids followed by a stop codon after the glycine residue at position 719.
A deletion of a guanine at position 2156 from the coding sequence of the EGFR gene.
A deletion of six amino acids from the epidermal growth factor receptor protein from the lysine at position 745 through the alanine at position 750.
A deletion of five amino acids from the epidermal growth factor receptor protein from the lysine at position 745 through the glutamic acid at position 749.
A deletion of 15 nucleotides from the coding sequence of the EGFR gene from position 2233 through 2247.
A deletion of five amino acids from the epidermal growth factor receptor protein from the glutamic acid at position 746 through the alanine at position 750.
A deletion of three amino acids from the epidermal growth factor receptor protein from the lysine at position 745 through the leucine at position 747.
A deletion of 15 nucleotides from the coding sequence of the EGFR gene from position 2236 through 2250.
A deletion of 15 nucleotides from the coding sequence of the EGFR gene from position 2235 through 2249.
A deletion of four amino acids from the epidermal growth factor receptor protein from the glutamic acid at position 746 through the glutamic acid at position 749.
A deletion of 12 nucleotides from the coding sequence of the EGFR gene from position 2235 through 2246.
A deletion of eight amino acids from the epidermal growth factor receptor protein from the glutamic acid at position 746 through the proline at position 753.
A deletion of three amino acids from the epidermal growth factor receptor protein from the glutamic acid at position 746 through the arginine at position 748.
A deletion of seven amino acids from the epidermal growth factor receptor protein from the glutamic acid at position 746 through the alanine at position 752.
A deletion of six amino acids from the epidermal growth factor receptor protein from the glutamic acid at position 746 through the threonine at position 751.
A deletion of 18 nucleotides from the coding sequence of the EGFR gene from position 2236 through 2253.
A deletion of 18 nucleotides from the coding sequence of the EGFR gene from position 2235 through 2252.
A deletion of the glutamic acid at position 746 from the epidermal growth factor receptor protein.
A deletion of three nucleotides from the coding sequence of the EGFR gene from position 2234 through 2246.
A deletion of four amino acids from the epidermal growth factor receptor protein from the leucine at position 747 through the alanine at position 750.
A deletion of nine amino acids from the epidermal growth factor receptor protein from the leucine at position 747 through the alanine at position 755.
A deletion of three amino acids from the epidermal growth factor receptor protein from the leucine at position 747 through the glutamic acid at position 749.
A deletion of nine nucleotides from the coding sequence of the EGFR gene from position 2239 through 2247.
A deletion of eight amino acids from the epidermal growth factor receptor protein from the leucine at position 747 through the lysine at position 754.
A deletion of 24 nucleotides from the coding sequence of the EGFR gene from position 2239 through 2262.
A deletion of seven amino acids from the epidermal growth factor receptor protein from the leucine at position 747 through the proline at position 753.
A deletion of six amino acids from the epidermal growth factor receptor protein from the leucine at position 747 through the serine at position 752.
A deletion of 18 nucleotides from the coding sequence of the EGFR gene from position 2239 through 2256.
A deletion of five amino acids from the epidermal growth factor receptor protein from the leucine at position 747 through the threonine at position 751.
A deletion of 15 nucleotides from the coding sequence of the EGFR gene from position 2239 through 2253.
A deletion of 15 nucleotides from the coding sequence of the EGFR gene from position 2240 through 2254.
A deletion of 15 nucleotides from the coding sequence of the EGFR gene from position 2238 through 2252.
A deletion of the leucine at position 747 from the epidermal growth factor receptor protein.
A deletion of six amino acids from the epidermal growth factor receptor protein from the arginine at position 748 through the proline at position 753.
A deletion of five amino acids from the epidermal growth factor receptor protein from the arginine at position 748 through the serine at position 752.
A deletion of nine amino acids from the epidermal growth factor receptor protein from the alanine at position 750 through the glutamic acid at position 758.
A deletion of 27 nucleotides from the coding sequence of the EGFR gene from position 2247 through 2273.
A deletion of five amino acids from the epidermal growth factor receptor protein from the alanine at position 750 through the lysine at position 754.
A deletion of 15 nucleotides from the coding sequence of the EGFR gene from position 2246 through 2260.
A deletion of eight amino acids from the epidermal growth factor receptor protein from the alanine at position 750 through the lysine at position 757.
A deletion of eight amino acids from the epidermal growth factor receptor protein from the threonine at position 751 through the glutamic acid at position 758.
A deletion of 24 nucleotides from the coding sequence of the EGFR gene from position 2250 through 2273.
A deletion of eight amino acids from the epidermal growth factor receptor protein from the serine at position 752 through the isoleucine at position 759.
A deletion of 24 nucleotides from the coding sequence of the EGFR gene from position 2254 through 2277.
A deletion of 24 nucleotides from the coding sequence of the EGFR gene from position 2253 through 2276.
A deletion of 18 amino acids from the epidermal growth factor receptor protein from the serine at position 752 through the valine at position 769.
A deletion of seven amino acids from the epidermal growth factor receptor protein from the proline at position 753 through the isoleucine at position 759.
A deletion of 21 nucleotides from the coding sequence of the EGFR gene from position 2257 through 2277.
A deletion of five amino acids from the epidermal growth factor receptor protein from the asparagine at position 756 through the leucine at position 760.
A deletion of the valine at position 774 from the epidermal growth factor receptor protein.
A deletion of four amino acids from the epidermal growth factor receptor protein from the isoleucine at position 789 through the leucine at position 792.
A deletion of the valine at position 834 from the epidermal growth factor receptor protein.
Total anomalous pulmonary venous return in which the pulmonary veins drain into the right atrium via the superior vena cava.
An insertion of the amino acid sequence proline-valine-alanine-isoleucine-lysine-isoleucine between the isoleucine at position 740 and the proline at position 741 of the epidermal growth factor receptor protein.
Total anomalous pulmonary venous return in which the pulmonary veins drain into the right atrium via the coronary sinus.
An insertion of 18 nucleotides, TCCCGTCGCTATTAAAAT, between position 2219 and 2220 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence lysine-isoleucine-proline-valine-alanine-isoleucine between the isoleucine at position 744 and the lysine at position 745 of the epidermal growth factor receptor protein.
An insertion of 18 nucleotides, TAAAATTCCCGTCGCTAT, between position 2231 and 2232 of the coding sequence of the EGFR gene.
An insertion of 18 nucleotides, AAAATTCCCGTCGCTATC, between position 2232 and 2233 of the coding sequence of the EGFR gene.
Total anomalous pulmonary venous return in which the common pulmonary vein connects to the portal venous system through the diaphragm.
Total anomalous pulmonary venous return in which the right and left pulmonary arteries drain into different sites.
An insertion of the amino acid sequence valine-proline-valine-alanine-isoleucine-lysine between the lysine at position 745 and the glutamic acid at position 746 of the epidermal growth factor receptor protein.
An insertion of 18 nucleotides, TTCCCGTCGCTATCAAGG, between position 2236 and 2237 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence glutamic acid-alanine-phenylalanine-glutamine between the aspartic acid at position 761 and the glutamic acid at position 762 of the epidermal growth factor receptor protein.
An insertion of 12 nucleotides, GAAGCCTTCCAG, between position 2283 and 2284 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence histidine-histidine between the tyrosine at position 764 and the valine at position 765 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence methionine-alanine-serine between the valine at position 765 and the methionine at position 766 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence alanine-isoleucine between the methionine at position 766 and the alanine at position 767 of the epidermal growth factor receptor protein.
An insertion of six nucleotides, guanine-cytosine-cytosine-adenine-thymine-adenine, between position 2232 and 2233 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence threonine-leucine-alanine between the alanine at position 767 and the serine at position 768 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, CGCTGGCCA, between position 2302 and 2303 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence phenylalanine-glutamine-glutamic acid-alanine between the alanine at position 763 and the tyrosine at position 764 of the epidermal growth factor receptor protein.
An insertion of 12 nucleotides, TCCAGGAAGCCT, between position 2302 and 2303 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence alanine-tryptophan-threonine between the serine at position 768 and the valine at position 769 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence valine-alanine-serine between the serine at position 768 and the valine at position 769 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, TGTGGCCAG, between position 2303 and 2304 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence alanine-serine-valine between the valine at position 769 and the aspartic acid at position 770 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, GCCAGCGTG, between position 2307 and 2308 of the coding sequence of the EGFR gene.
An insertion of nine nucleotides, CCAGCGTGG, between position 2308 and 2309 of the coding sequence of the EGFR gene.
Cholestasis that results from prolonged total parenteral nutrition. It is caused by diminished bile flow from the liver into the duodenum. It may result in cirrhosis and liver failure. Preterm infants are most susceptible to liver damage.
A complex substitution where the deletion of the nucleotide sequence adenine-cytosine at positions 2309 and 2310 of the coding sequence of the EGFR gene is followed by the insertion of 11 nucleotides, CCAGCGTGGAT.
An insertion of the amino acid sequence cysteine-valine between the valine at position 769 and the aspartic acid at position 770 of the epidermal growth factor receptor protein.
An insertion of six nucleotides, thymine-guanine-cytosine-guanine-thymine-guanine, between position 2307 and 2308 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence aspartic acid-asparagine-valine between the valine at position 769 and the aspartic acid at position 770 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, GACAACGTG, between position 2307 and 2308 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence glycine-serine-valine between the valine at position 769 and the aspartic acid at position 770 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, GCAGCGTGG, between position 2308 and 2309 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence glycine-valine between the valine at position 769 and the aspartic acid at position 770 of the epidermal growth factor receptor protein.
A rare congenital or acquired abnormality characterized by the presence of a web-like thin layer of tissue that narrows the lumen of the trachea. It may result in wheezing, dyspnea, and respiratory failure.
An insertion of the amino acid sequence glycine-valine-valine between the valine at position 769 and the aspartic acid at position 770 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, GGGTCGTGG, between position 2308 and 2309 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence methionine-alanine-serine-valine-aspartic acid between the valine at position 769 and the aspartic acid at position 770 of the epidermal growth factor receptor protein.
An insertion of 15 nucleotides, ATGGCCAGCGTGGAC, between position 2307 and 2308 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence alanine-proline-tryptophan between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, GCACCGTGG, between position 2310 and 2311 of the coding sequence of the EGFR gene.
An insertion of the amino acid aspartic acid between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence aspartic acid-glycine between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of six nucleotides, adenine-cytosine-guanine-guanine-cytosine-guanine, between position 2308 and 2309 of the coding sequence of the EGFR gene.
An insertion of the amino acid glycine between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of three nucleotides, guanine-guanine-thymine, between position 2310 and 2311 of the coding sequence of the EGFR gene.
An insertion of three nucleotides, guanine-guanine-cytosine, between position 2310 and 2311 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence glycine-aspartic acid between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of six nucleotides, guanine-guanine-guanine-guanine-adenine-cytosine, between position 2310 and 2311 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence glycine-leucine between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of six nucleotides, guanine-guanine-guanine-thymine-thymine-adenine, between position 2310 and 2311 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence methionine-alanine-threonine-proline between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of 12 nucleotides, TGGCCACCCCCA, between position 2311 and 2312 of the coding sequence of the EGFR gene.
An insertion of the amino acid asparagine between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of three nucleotides, adenine-adenine-cytosine, between position 2310 and 2311 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence asparagine-proline-histidine between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, AACCCCCAC, between position 2310 and 2311 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence serine-valine-aspartic acid between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, GCGTGGACA, between position 2311 and 2312 of the coding sequence of the EGFR gene.
An insertion of nine nucleotides, AGCGTGGAC, between position 2310 and 2311 of the coding sequence of the EGFR gene.
Vesicoureteral reflux in which there is urine reflux into the ureter only.
Vesicoureteral reflux in which there is urine reflux into the ureter and renal pelvis. There is no dilatation of the ureter and the calyces.
Vesicoureteral reflux in which there is urine reflux into the ureter and renal pelvis. Mild dilatation of the ureter and the calyces is present.
Vesicoureteral reflux in which there is urine reflux into the ureter and renal pelvis. Moderate dilatation of the ureter and the calyces is present.
Vesicoureteral reflux in which there is urine reflux into the ureter and renal pelvis. Severe tortuosity and dilatation of the ureter and the calyces are present.
An insertion of the amino acid sequence serine-valine-proline between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence serine-valine-glutamine between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
A change in the amino acid composition of the epidermal growth factor receptor protein where a frameshift mutation results in the insertion of 60 non-canonic amino acids followed by a stop codon after the aspartic acid residue at position 770.
An insertion of 14 nucleotides, ATGGCCAGCGTGGA, between position 2309 and 2310 of the coding sequence of the EGFR gene.
An insertion of the amino acid histidine between the asparagine at position 771 and the proline at position 772 of the epidermal growth factor receptor protein.
An insertion of the amino acid asparagine between the asparagine at position 771 and the proline at position 772 of the epidermal growth factor receptor protein.
An insertion of 3 nucleotides, AAC, between position 2313 and 2314 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence aspartic acid-histidine-proline between the proline at position 772 and the histidine at position 773 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence proline-arginine between the proline at position 772 and the histidine at position 773 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence aspartic acid-asparagine-proline between the proline at position 772 and the histidine at position 773 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence glutamine-valine between the proline at position 772 and the histidine at position 773 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence tyrosine-asparagine-proline between the proline at position 772 and the histidine at position 773 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence threonine-histidine-proline between the proline at position 772 and the histidine at position 773 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, GACACACCC, between position 2315 and 2316 of the coding sequence of the EGFR gene.
An insertion of the amino acid glycine between the histidine at position 773 and the valine at position 774 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence glycine-histidine between the histidine at position 773 and the valine at position 774 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence glycine-asparagine-proline-histidine between the histidine at position 773 and the valine at position 774 of the epidermal growth factor receptor protein.
An insertion of 12 nucleotides, GCAACCCCCACG, between position 2320 and 2321 of the coding sequence of the EGFR gene.
An insertion of the amino acid histidine between the histidine at position 773 and the valine at position 774 of the epidermal growth factor receptor protein.
An insertion of three nucleotides, cytosine-adenine-cytosine, between position 2319 and 2320 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence asparagine-proline-histidine between the histidine at position 773 and the valine at position 774 of the epidermal growth factor receptor protein.
An insertion of nine nucleotides, AACCCCCAC, between position 2319 and 2320 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence proline-histidine between the histidine at position 773 and the valine at position 774 of the epidermal growth factor receptor protein.
An insertion of six nucleotides, cytosine-cytosine-cytosine-cytosine-cytosine-adenine, between position 2318 and 2319 of the coding sequence of the EGFR gene.
An insertion of six nucleotides, cytosine-cytosine-cytosine-cytosine-adenine-cytosine, between position 2319 and 2320 of the coding sequence of the EGFR gene.
An insertion of the amino acid sequence histidine-valine between the valine at position 774 and the cysteine at position 775 of the epidermal growth factor receptor protein.
An insertion of cytosine-adenine-cytosine-guanine-thymine-guanine between position 2322 and 2323 of the coding sequence of the EGFR gene.
An insertion of six nucleotides, cytosine-cytosine-adenine-cytosine-guanine-thymine, between position 2321 and 2322 of the coding sequence of the EGFR gene.
A complex nucleotide substitution where the deletion of guanine at position 2322 is followed by the insertion of seven nucleotides, cytosine-cytosine-adenine-cytosine-guanine-thymine-guanine, into the coding sequence of the EGFR gene.
A benign dermal neoplasm comprising of round cells, resembling histiocytes. The tumor commonly occurs in young dogs and may regress spontaneously.
A benign epithelial neoplasm of the pituitary gland.
An ovarian neoplasm comprising Sertoli cells in which the malignancy status has not been established.
A benign neoplasm of the rodent Zymbal's gland with sebaceous and/or squamous differentiation.
A malignant neoplasm of the rodent Zymbal's gland with sebaceous and/or squamous differentiation.
Cataract that results from the aging process, an injury, or as a manifestation of a systemic disorder.
Chylothorax that results from malignancies (usually lymphoma), trauma to the thoracic duct, tuberculosis, or sarcoidosis.
Rickets that is caused by vitamin D deficiency, hypocalcemia, or renal failure.
An orally bioavailable small-molecule inhibitor of mitogen-activated protein kinase kinase (MAP2K, MAPK/ERK kinase, or MEK) 1 and 2 with potential antineoplastic activity. MEK1/2 inhibitor AS703988/MSC2015103B selectively binds to and inhibits the activity of MEK1/2, preventing the activation of MEK1/2-dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK1/2 are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway that regulates cell growth and are often upregulated in a variety of tumor cell types.
A 40-carbon hydrocarbon precursor of carotenoids radiolabeled to carbon C 13 and potentially used for tracer purposes of phytoene in vivo. Upon administration, phytoene is taken up and accumulates in various tissues. Upon imaging of the radioisotope, the distribution patterns and metabolism of phytoene can be further elucidated which may aid in the understanding of the bioactivity of this agent. Phytoene is a colorless precursor of many carotenoids, including the antioxidant lycopene.
A 40-carbon hydrocarbon precursor of carotenoids radiolabeled to carbon C 13 and potentially used for tracer purposes of phytofluene in vivo. Upon administration, phytofluene is taken up and accumulates in various tissues. Upon imaging of the radioisotope, the distribution patterns and metabolism of phytofluene can be further elucidated which may aid in the understanding of the bioactivity of this agent. Phytofluene is a colorless precursor of many carotenoids, including the antioxidant lycopene.
A form of sickle cell thalassemia characterized by the absence of hemoglobin A. Patients usually have severe anemia identical to that seen in sickle cell disease.
Peripheral blood progenitor cells (PBPC) primed with a recombinant form of the human granulocyte colony-stimulating factor (filgrastim). As a hematopoietic growth factor, filgrastim is able to mobilize hematopoietic progenitor cells (HPCs) into the peripheral blood which allows for an increased number of HPCs upon collection by leukapheresis. Administration of filgrastim-primed PBPCs following hematopoietic stem cell transplantation provides increased numbers of progenitor cells which may prevent pancytopenia and relapse.
A mild form of sickle cell thalassemia characterized by the presence of hemoglobin S and a small amount of hemoglobin A in the red blood cells. It is characterized by the presence of small red blood cells and mild anemia.
A microscopic finding indicating the presence in a sample of tissue that resembles endometrial tissue.
A malformation in any part of the large intestine that is present at birth.
An abnormality of the superior or inferior vena cava that is present at birth. Representative examples include persistent left superior vena cava, absence of infrarenal inferior vena cava, or absence of the entire inferior vena cava.
Herniation of spinal cord tissue and meninges through a defect in the sacral region of the vertebral column. The protrusion of the tissue is flush with the level of the skin surface.
Blockage of the opening between the ureter and the bladder resulting in the reduction or prevention of the urine flow from the ureter to the bladder.
An acyanotic congenital cardiovascular abnormality characterized by the transposition of the aorta and the pulmonary artery.
Episodes of cyanosis that result from breath holding spells in response to anger or frustration, during childhood. These episodes usually resolve in a few seconds.
The formation of tissue in the lumen of the ileum that results in partial obstruction.
An orally available prodrug of PSI-6130 which is a selective cytidine nucleoside analogue and non-cytotoxic hepatitis C virus (HCV) polymerase inhibitor. After intracellular uptake, mericitabine is phosphorylated into two active triphosphate metabolites, which disable HCV RNA-dependent RNA polymerase (non-structural protein 5B; NS5B) upon binding. This results in the blockage of viral HCV RNA production and thus viral replication. This agent has a high barrier to resistance, however, a substitution mutation (S282T) on HCV NS5B impairs mericitabine's activity significantly.
Congenital abnormalities, mainly cardiovascular malformations, which develop in a fetus when the mother uses lithium medication during pregnancy.
A rare metabolic disorder characterized by the deficiency of mitochondrial NADH dehydrogenase component of complex I. Signs and symptoms include cardiomyopathy, encephalopathy, enlarged head, and progressive leukodystrophy.
A syndrome that is defined by signs and symptoms related to abrupt or gradual stoppage of opioids use. They include strong cravings, sweating, nausea, vomiting, irritation, anxiety, muscle pain, dilated pupils and insomnia.
An abnormal communication between the rectum, bladder, and vagina.
Retinopathy of prematurity located in zone 1 of the retina.
Retinopathy of prematurity located in zone 2 of the retina.
Retinopathy of prematurity located in zone 3 of the retina.
Bronchopulmonary dysplasia that results in severe respiratory complications. The infants with severe symptoms are usually premature, have low birth weight, and the oxygen and ventilation support requirements are increased.
A diverse group of congenital cardiovascular abnormalities that share one characteristic, the presence of a single functional cardiac ventricle.
A congenital deficiency of one of the surfactant proteins.
Deficiency of surfactant protein C. It leads to progressive lung fibrosis.
Deficiency of surfactant protein ABCA3. It leads to respiratory distress that is often fatal.
Deficiency of surfactant protein D. When present in normal amounts, this protein offers protection against pulmonary infection and inflammation.
Deficiency of surfactant protein A. When present in normal amounts, this protein protects the lungs against a variety of bacteria, viruses, and fungi.
A rare infantile hemangioma in the airway, usually in the subglottic area or trachea. It may or may not be associated with cutaneous lesions. It is a potentially life-threatening condition and the infant should be closely monitored for signs of airway disease.
A cancer cell vaccine composed of autologous human Langerhans-type dendritic cells (also known as Langerhans cells or LCs) that are electroporated with mRNA encoding full-length murine tyrosinase-related peptide 2 (TRP2), with potential antineoplastic and immunomodulating activities. Upon vaccination, the TRP2 mRNA-electroporated autologous Langerhans-type dendritic cell vaccine may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against TRP2-expressing tumor cells. TRP2, a tautomerase involved in the synthesis of melanin, is only expressed in melanomas, melanocytes, and the retina. The LCs are differentiated from CD34 positive hematopoietic progenitor cells.
A finding that indicates the presence of immature retinal vessels as a result of prematurity.
A cancer vaccine containing autologous dendritic cells (DCs) that are pulsed with mRNA encoding human telomerase reverse transcriptase (hTERT) and survivin peptide, with potential immunostimulatory and antineoplastic activities. Upon administration, hTERT mRNA/survivin peptide-double-loaded autologous dendritic cell vaccine may elicit an immune response against cancer cells expressing hTERT and survivin by activating cytotoxic T-cells (CTLs), natural killer cells (NKs), and B-lymphocytes. The tumor associated antigens (TAAs) hTERT, the catalytic subunit of human telomerase, and survivin, a member of the inhibitor of apoptosis (IAP) family of proteins, may be upregulated in certain tumor cell types and play key roles in tumor cell growth and survival.
A finding that indicates the presence of immature retinal vessels in zone 1 of the retina.
A finding that indicates the presence of immature retinal vessels in zone 2 of the retina.
A finding that indicates the presence of immature retinal vessels in zone 3 of the retina.
Bowel perforation in utero that may result in meconium peritonitis.
An orally available proprietary aqueous extract from the North American ginseng (Panax quinquefolius) dried root, primarily containing poly-furanosyl-pyranosyl-saccharides, with potential immunostimulating activity. Upon administration, North American ginseng extract AFX-2 may stimulate the proliferation and activation of B-lymphocytes and stimulates IgG production by B cells. Also, this agent induces maturation of dendritic cells, induces T cell proliferation and activates peritoneal exudate macrophages leading to an increase in the production of the cytokines interleukin -1 and -6, tumor necrosis factor-alpha, interferon-gamma and nitric oxide.
A human monoclonal antibody directed against the WNT antagonist dickkopf homolog 1 (DKK1), with potential anti-osteolytic activity. Anti-DKK1 monoclonal antibody LY2812176 binds to and inhibits DKK1, thereby restoring signaling through the WNT pathway, which may result in osteoblast differentiation and activation within the bone matrix and the reversal of tumor-induced osteolytic disease. DKK1, overexpressed by myeloma cells, is an inhibitor of the WNT signaling pathway and prevents the mediated formation of bone.
A derivative of the amino acid histidine, formed in the mammalian skin from trans-urocanic acid upon ultraviolet radiation, and protodynamic agent, with potential anti-inflammatory and antiproliferative activity. Upon intravesical instillation of cis-urocanic acid (cis-UCA), this agent is protonated at the imidazolyl moiety in the mildly acidic extracellular tumor environment and penetrates into the cancer cell. Once inside the cell and due to the slightly alkaline pH inside the tumor cell, cis-UCA is deprotonated, i.e. the imidazolyl proton is released into the cytosol which eventually raises the intracellular acidity. This acidification impairs many cellular processes, such as metabolic activity, and may lead to cell cycle arrest, an induction of cellular apoptosis and necrotic cell death. In addition, cis-UCA enhances ERK and JNK signaling pathways by inhibiting the activity of serine/threonine and tyrosine phosphatases.
A cancer vaccine containing the three frame shift peptides (FSP) AIM2(-1), HT001(-1) and TAF1B(-1), with potential immunomodulating activity. Upon administration, the AIM2(-1)/HT001(-1)/TAF1B(-1) FSP vaccine may induce an immune response against microsatellite instability (MSI) colorectal cancer-associated antigens. Frame shift mutations of AIM2 (absent in melanoma 2, an interferon-inducible protein), HT001 (asteroid homolog 1 or ASTE1, with an unknown function) and TAF1B (TATA box-binding protein-associated RNA polymerase I B, a transcription factor) are seen in MSI-positive colorectal cancers and may be associated with malignant transformation, tumor progression and the presence of tumor-infiltrating lymphocytes. These FSPs all have one-base deletions.
A heparin derivative in which the 2-O and 3-O sulfate groups of heparin are removed and that lacks anticoagulant activity, with potential anti-inflammatory, immodulatory and antineoplastic activities. Upon administration, 2-O, 3-O desulfated heparin (ODSH) binds to both chemokine stromal cell-derived factor 1 (SDF-1 or CXCL12) and CXC chemokine receptor 4 (CXCR4). This prevents the interaction of CXCL12 with CXCR4, blocks CXCR4 activation, and may result in decreased proliferation and migration in CXCR4-overexpressing tumor cells. In addition, inhibition of CXCL12/CXCR4 interaction may induce mobilization of hematopoietic cells from the bone marrow into the blood. In addition, ODSH prevents the interaction of the receptor for advanced glycation end-products (RAGE) with its ligands, including advanced glycation end-products (AGEs), Mac-1(CD11b/CD18), the nuclear pro-inflammatory protein high mobility group box protein-1 (HMGB-1), carboxymethyl lysine-bovine serum albumin (CML-BSA) and members of the S100 calgranulin family. In addition, this agent inhibits the enzymes heparanase, cathepsin G, and human leukocyte elastase, which are involved in inflammation and metastasis. ODSH also binds to platelet factor 4 (PF4 or CXCL4) and may prevent PF4's inhibitory effect on platelet production. Altogether, this may inhibit tumor cell invasiveness and metastasis. ODSH also binds to platelet factor 4 (PF4 or CXCL4) and may prevent PF4's inhibitory effect on platelet production. This may increase platelet production. Unlike heparin, this agent does not induce heparin-induced thrombocytopenia (HIT). RAGE, a receptor belonging to the immunoglobulin superfamily, plays a key role in inflammation and is overexpressed in a variety of cancers. CXCR4 is a chemokine receptor belonging to the G protein-coupled receptor (GPCR) family that plays an important role in chemotaxis, chemoresistance and angiogenesis, and is upregulated in several tumor cell types. The interaction between CXCL12/CXCR4 induces retention of hematopoietic cells in the bone marrow.
Allogeneic tri-viral specific, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus (Ad), cytotoxic T-lymphocytes (tV-CTLs) expressing a chimeric antigen receptor (CAR) specific for disialoganglioside GD2 with potential antineoplastic activity. Tri-virus/GD2-specific allogeneic CTLs are produced by transducing tV-CTLs with a GD2-specific CAR retroviral vector. Upon administration, after an allogeneic hematopoietic stem cell transplant, these CTLs may be selective towards EBV, CMV, and Ad-infected cells and GD2-expressing tumor cells. The human glycosphingolipid GD2 is a tumor associated antigen overexpressed on the surface of all tumors of neuroectodermal origin.
A radiotracer composed of a cyclic triazole-containing the Arg-Gly-Asp (RGD) peptide (RGD-K5) radiolabeled with fluorine F 18, with potential alphaVbeta3 integrin imaging activity upon positron emission topography (PET). Upon administration, the RGD moiety of fluorine F 18 RGD-K5 selectively binds to alphaVbeta3 integrin. During PET, alphaVbeta3-expressing tumor cells can be visualized and the degree of tumor angiogenesis can be determined. AlphaVbeta3 integrin, a cell adhesion and signaling receptor, is upregulated in tumor vessel endothelial cells and has been associated with neovascularization, differentiation, proliferation of tumor cells, and metastasis.
An orally active p38 mitogen-activated protein kinase (MAPK) inhibitor with potential immunomodulating, anti-inflammatory, and antineoplastic activity. Upon administration, LY3007113 inhibits the activity of p38, thereby preventing p38 MAPK-mediated signaling. This may result in the inhibition of the production of proinflammatory cytokines and the induction of tumor cell apoptosis. p38 MAPK, a serine/threonine protein kinase often upregulated in cancer cells, plays a crucial part in the production of a variety of cytokines involved in inflammation and cellular proliferation such as tumor necrosis factor (TNF) and interleukin (IL)-1 and -6.
A congenital vascular abnormality that affects the great vessels and/or aortic arch. Representative examples include double aortic arch, aortic coarctation, and absence of a pulmonary artery.
A synthetic, soluble prodrug of beta-lapachone, a poorly soluble, ortho-naphthoquinone with potential antineoplastic and radiosensitizing activity. ARQ 761 is converted to beta-lapachone (b-lap) in vivo. When b-lap is activated by NAD(P)H:quinone oxidoreductase-1 (NQO1) this agent creates a futile oxidoreduction, generating highly reactive oxygen species (ROS) that results in DNA damage. The activation of b-lap also causes hyperactivation of poly (ADP-ribose) polymerase-1 (PARP-1), an enzyme that facilitates DNA repair, accompanied by rapid depletion of NAD+/ATP nucleotide levels. As a result, a caspase-independent and endoplasmic reticulum (ER) stress-induced mu-calpain-mediated cell death occurs in NQO1-overexpressing tumor cells. In addition, b-lap induces expression of the checkpoints activator E2F transcription factor 1 (E2F1) and thereby activates the E2F1-mediated checkpoint pathway that directly triggers apoptosis. As ARQ 761 is soluble and requires less solvent, this formulation may cause less hemolytic anemia associated with administration of the synthetic b-lap ARQ 501.
A mouthwash containing honey with potential antimucositis activity. Upon rinsing with this mouthwash, honey modulates the production of pro-inflammatory cytokines which may kill bacteria thus potentially preventing inflammation of the mucosal membranes and may decrease chemotherapy- and/or radiation-induced oral mucositis. In addition, honey may have a protective and healing effect on the oral mucosa.
The hydrochloride salt form of icotinib, an orally available quinazoline-based inhibitor of epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Icotinib selectively inhibits the wild-type and several mutated forms of EGFR tyrosine kinase. This may lead to an inhibition of EGFR-mediated signal transduction and may inhibit cancer cell proliferation. EGFR, a receptor tyrosine kinase, has been upregulated in a variety of cancer cell types.
A tropomyosin receptor kinase (TRK) inhibitor with potential antineoplastic activity. AZD7451 binds to TRK, thereby preventing the neurotrophin-TRK interaction and subsequent TRK activation. This may eventually result in an inhibition of tumor cell proliferation in TRK-expressing tumor cells. TRK, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth, invasion and survival.
A chimeric monoclonal antibody against a Lewis-A-like glycotope (AbGn-7 antigen) with potential immunomodulating and antineoplastic activities. Monoclonal antibody AbGn-7 targets and binds to the carbohydrate AbGn-7 antigen on the cell surface of tumor cells and may induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), thereby killing AbGn-7-epitope positive tumor cells. AbGn-7 antigen is expressed on a variety of tumor cell types, including human colorectal, pancreatic and gastric tumor cells.
A lozenge containing lyophilized black raspberry with potential antioxidant, pro-apoptotic, anti-angiogenic and chemopreventive activities. In addition to vitamins, minerals and phytosterols, black raspberries are rich in phenolic acids, such as gallic acid, ellagic acid, proanthocyanidins, and flavonoids. The anthocyanins appear to contribute significantly to this agent's effects. Anthocyanins inhibit both the activation of several signal transduction pathways, including the mitogen-activated protein kinase-mediated pathways, and certain transcription factors, such as nuclear factor kappa B (NF-kB), activator protein-1 (AP-1) complex, and nuclear factor in activated T-cells (NFAT). This inhibitory activity modulates the expression of downstream target genes that are upregulated in a variety of cancer cell types, including inducible nitric oxide synthase, cyclooxygenase-2, vascular endothelial growth factor and the anti-apoptotic protein survivin.
A saliva substitute (or artificial saliva) containing lyophilized black raspberry with potential antioxidant, pro-apoptotic and chemopreventive activities. In addition to vitamins, minerals and phytosterols, black raspberries are rich in flavonols of which the anthocyanins appear to contribute significantly to this agent's chemopreventive effects. Anthocyanins inhibit the activation of several signal transduction pathways, including the mitogen-activated protein kinase-mediated pathways, and certain transcription factors, such as nuclear factor kappa B (NF-kB), activator protein-1 (AP-1) complex, and nuclear factor in activated T-cells (NFAT). This in turn modulates the expression of downstream target genes that are upregulated in a variety of cancer cell types, including inducible nitric oxide synthase, cyclooxygenase-2, vascular endothelial growth factor and the anti-apoptotic protein survivin.
A proprietary preparation of small interfering DNA (siDNA) molecules with potential chemo/radiosensitizing activity. By mimicking DNA double strand breaks (DSBs), DNA-dependent protein kinase-targeting siDNA DT01 inhibits the non-homologous end joining (NHEJ) process, one of the main DNA repair mechanisms, via binding to and activating DNA-dependent protein kinase (DNA-PK), a core component of the NHEJ complex. DNA-PK activation causes hyper-phosphorylation of histone variant H2AX on DNA and results in a different phosphorylated pattern of H2AX upon ionizing radiation treatment. This ultimately interferes with the repair of DNA DSBs during chemo- or radiotherapy, thereby increasing tumor cell death. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy.
A radioimmunoconjugate composed of basiliximab, a chimeric, mouse-human monoclonal antibody directed against the alpha subunit of interleukin-2 receptor (IL-2R alpha, CD25 or Tac antigen), and labeled with yttrium y 90, with potential antineoplastic activity. The basiliximab moiety of yttrium Y 90 basiliximab selectively binds to IL-2R alpha expressed on the surface of activated T-lymphocytes, thereby preventing IL-2 binding and blocking the IL-2-mediated activation of lymphocytes. The yttrium y 90 moiety selectively delivers a cytotoxic dose of beta radiation to lymphocytes that express the IL-2 receptor. This may prevent T cell-mediated activation of the immune system against a certain transplant and may prevent transplant rejection.
A radioimmunoconjugate composed of a humanized monoclonal antibody (MoAb) OTSA101 against FZD10 and labeled with yttrium y 90, with potential antineoplastic activity. The MoAb moiety of yttrium Y 90-labeled anti-FZD10 monoclonal antibody OTSA101 binds to FZD10, thereby delivering a cytotoxic dose of beta radiation to FZD10 positive tumor cells. FZD10 (also called CD350), a member of the Frizzled family of G protein-coupled receptors that is involved in the Wnt/beta-catenin/TCF signaling pathway, is overexpressed in a variety of cancer cell types but undetectable in normal, healthy human tissues except for the placenta.
A radioimmunoconjugate composed of a humanized monoclonal antibody IgG1 directed against the epidermal growth factor receptor (EGFR) and labeled with the radioisotope indium In 111, with potential radioimaging activity. Indium In 111 anti-EGFR monoclonal antibody ABT-806 binds to a specific epitope of either wild-type or EGFR variant III mutant on tumor cells, thereby allowing imaging of EGFR-expressing tumor cells using gamma scintigraphy. ABT-806 is the humanized version derived from the predecessor chimeric monoclonal antibody 806. EGFR, a receptor tyrosine kinase overexpressed on the cell surfaces of many tumor cell types, plays a key role in tumor cell proliferation.
A topical emulsion containing beta-glucan (5%), alginate, hyaluronic acid, squalene and avocado oil, with cutaneous protective activity. Upon topical application of beta-glucan/alginate/hyaluronic acid/squalene/avocado oil-containing emulsion, the naturally-occurring polysaccharide beta-glucan acts as an immunomodulator by activating the innate immune response, in particular through the activation of macrophages and migration of neutrophils. Alginate acts as a moisturizer and supports skin healing. Hyaluronic acid, squalene and avocado oil provide barrier protection, help maintain skin integrity and are natural emollients and moisturizers. This emulsion may accelerate wound healing and may prevent radiation-induced dermatitis.
An intravitreal implant containing the corticosteroid dexamethasone embedded in a biodegradable polymer matrix, with anti-inflammatory and macular edema relieving activity. Upon insertion into the vitreous cavity, dexamethasone intravitreal implant is dissolved slowly and dexamethasone is released over an extended period of time. Dexamethasone inhibits inflammation thereby preventing leakage from the capillaries and a reduction of retinal edema. This may ultimately prevent vision impairment.
An orally bioavailable inhibitor of the serine/threonine protein kinase AKT (protein kinase B) with potential antineoplastic activity. AKT inhibitor ARQ 092 binds to and inhibits the activity of AKT in a non-ATP competitive manner, which may result in the inhibition of the PI3K/AKT signaling pathway. This may lead to the reduction in tumor cell proliferation and the induction of tumor cell apoptosis. The AKT signaling pathway is often deregulated in cancer and is associated with tumor cell proliferation, survival and migration.
A compound or product that was available prior to the passage of the 1938 Federal Food, Drug and Cosmetic Act.
A rare, slow-growing, painless tumor of infancy and early childhood that usually affects the distal extremities. It is characterized by the presence of alternating bands of mature adipose tissue and spindle-cell fibrous tissue, without destruction of the adipose tissue architecture. It does not metastasize, however the rate of local recurrences is high.
A preparation of allogeneic Epstein-Barr virus (EBV)- and human cytomegalovirus (CMV)-specific CD8+ central memory-derived T effector-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) anti-CD19/CD3 zeta chain fusion protein coupled to the intracellular signal domain of CD28 antigen, with potential immunostimulating, anti-viral and antineoplastic activities. Upon infusion, allogeneic CD19-specific CAR-modified CD8+ central memory-derived virus-specific T cells directs the T-lymphocytes to CD19-expressing tumor cells, stimulating a selective toxicity to tumor cells which may eventually result in tumor cell lysis. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. The viral specific T-cells exert antiviral immunity.
An immunoconjugate consisting of a human monoclonal antibody directed against the deletion-mutant of epidermal growth factor receptor, EGFRvIII, conjugated via a non-cleavable linker to the cytotoxic agent maytansinoid DM1, with potential antineoplastic activity. The monoclonal antibody moiety of this immunoconjugate binds to EGFRvIII on tumor cell surfaces. After internalization, the DM1 moiety binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics and inhibiting cell division and the proliferation of cancer cells that express the EGFRvIII mutant. EGFRvIII, a deletion mutation of exons 2-7 in the epidermal growth factor receptor gene, is overexpressed by a variety of cancers, including glioblastoma multiforme, non-small lung carcinoma, and breast carcinoma.
A bi-functional alkylating agent, with potential antineoplastic activity. Upon administration, VAL-083 crosses the blood brain barrier (BBB) and appears to be selective for tumor cells. This agent alkylates and crosslinks DNA which ultimately leads to a reduction in cancer cell proliferation. In addition, VAL-083 does not show cross-resistance to other conventional chemotherapeutic agents and has a long half-life in the brain.
A synbiotic supplement containing beta-1,3-glucan, bacteria Lactobacillus casei (L. casei) and Bifidobacterium lactis (B. lactis), with potential immunomodulating activity. The naturally-occurring bacterial components in this dietary supplement may improve digestion and help maintain adequate colonization of the gastrointestinal (GI) tract by modulating the composition of the normal microflora. During colonization of the GI tract, the bacteria may form a protective intestinal barrier, thereby preventing attachment of potential pathogens. Both the probiotics and beta-glucan have been shown to stimulate the immune system. This supplement also contains several vitamins and other insoluble polysaccharides.
A cancer peptide vaccine comprised of a human leukocyte antigen (HLA) A2/A3 restricted HER2/neu (ERBB2) peptide from the extracellular domain of the HER2 protein (E75 peptide) and combined with the immunoadjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential immunomodulating and antineoplastic activity. Upon intradermal injection, nelipepimut-S plus GM-CSF vaccine may induce a specific cytotoxic T-lymphocyte (CTL) response against HER2/neu-expressing tumor cell types. HER2/neu, a tumor-associated antigen and a member of the epidermal growth factor receptor family of tyrosine kinases, is overexpressed in various tumor cell types. GM-CSF potentiates the antitumor immune response.
A lozenge containing an extract from the Lactobacillus brevis (L. brevis) with potential anti-inflammatory activity. As L. brevis CD2 contains high levels of arginine deiminase, which catalyzes the conversion of arginine to citrulline and ammonia, administration of this lozenge leads to hydrolysis of arginine in the oral cavity. The growth of bacteria, which depends on arginine, is halted, polyamine biosynthesis is reduced and the production of nitric oxide (NO) is reduced. The reduction in NO generation may further prevent inflammation in the oral cavity. Therefore, this agent may be able to reduce chemo- and radiotherapy-induced mucositis.
A nutritional supplement comprised of prebiotic and probiotic ingredients, with potential immunomodulating and gastrointestinal (GI) flora restoring activity. Upon ingestion of the synbiotic supplement, the prebiotics and probiotics work synergistically in the GI tract, thereby modulating the GI flora ecosystem and may improve the functions of the intestinal barrier. In addition, synbiotics may have a beneficial effect on the immune system.
A constellation of neurobehavioral features observed in a neonate following cessation or reduction of postnatal exposure to opioids.
The participant is a probable case for the phenotype under consideration.
The evolution of a low-grade neoplastic pathologic process to a high grade malignancy.
An orally available DNA cancer vaccine containing an attenuated strain of the bacterium Salmonella typhimurium encoding murine vascular endothelial growth factor receptor 2 (VEGFR-2) (VXM01), with potential immunomodulating, anti-angiogenic and antineoplastic activity. Upon oral administration and successful transduction, VEGFR-2 DNA vaccine VXM01 expresses VEGFR-2 in addition to inducing the expression of T-cell activation markers, such as CD25, interleukin-2, the early T-cell activation antigen CD69 and the lymphocyte function-associated antigen LFA-2. The immune response targets the fast growing VEGFR-2 expressing endothelial cells found in the tumor vasculature, thereby blocking angiogenesis which may ultimately inhibit tumor cell proliferation. VEGFR-2 is a receptor tyrosine kinase overexpressed on proliferating endothelial cells in the tumor vasculature.
A 45-mer L-stereoisomer RNA oligonucleotide linked to a 40 kDa polyethyleneglycol that targets the small chemokine stromal cell-derived factor 1 (SDF-1 or CXCL12) with potential antineoplastic and hematopoietic stem cell-mobilization activities. SDF-1 targeted agent NOX-A12 specifically binds to SDF-1 thereby preventing the binding of SDF-1 to its receptors CXCR4 and CXCR7 blocking the subsequent receptor activation. This may prevent angiogenesis, tumor cell proliferation, invasion and metastasis and could sensitize tumor cells to chemotherapy. In addition, inhibition of SDF-1/CXCR4 interaction may induce mobilization of hematopoietic cells from the bone marrow into blood. The unique mirror-image configuration of this agent renders it resistant to hydrolysis and does not hybridize with native nucleic acids. Furthermore, this agent does not induce the innate immune response and has shown a favorable immunogenicity profile.
An orally available, small molecule inhibitor of PIM kinases with potential antineoplastic activity. Pan-PIM kinase inhibitor AZD1208 inhibits the activities of PIM1, PIM2 and PIM3 serine/threonine kinases, which may result in the interruption of the G1/S phase cell cycle transition, thereby causing cell cycle arrest and inducing apoptosis in cells that overexpress PIMs. The growth inhibition of several leukemia cell lines by this agent is correlated with the expression levels of PIM1, which is the substrate of STAT transcription factors. PIM kinases are downstream effectors of many cytokine and growth factor signaling pathways and are upregulated in various malignancies.
Breast carcinoma that develops in the opposite breast of a patient with an already diagnosed primary breast carcinoma.
An unbalanced translocation between chromosomes 1 and 19. It is observed in oligodendrogliomas and results in the co-deletion of 1p and 19q.
A cutaneous gel preparation containing an extract from Solanum incanum with potential antineoplastic activity. SR-T100 gel contains high amounts of the steroidal alkaloid glycoside solamargine. Solamargine is able to upregulate expression of tumor necrosis factor receptors 1 (TNFR1) and 6 (TNFRSF6 or Fas), and their signaling adaptors TNFR1-associated death domain, and Fas-associated death domain. In addition, this agent is able to upregulate expression of apoptosis promoter Bax, and suppress the expression of the anti-apoptotic proteins Bcl-xL and Bcl-2. Altogether, this induces apoptosis in tumor cells and may lead to an inhibition of tumor cell proliferation.
Slightly less than normal amount of blood that is forced from the heart ventricle to produce cardiac output. Quantitatively, the ejection fraction is considered between 40% to 49%.
Moderately less than normal amount of blood that is forced from the heart ventricle to produce cardiac output. Quantitatively, the ejection fraction is considered between 30% to 39%.
Severely less than normal amount of blood that is forced from the heart ventricle to produce cardiac output. Quantitatively, the ejection fraction is considered less than 30%.
A pathologically high percentage of blood that is forced from the heart ventricle to produce cardiac output. This is often the result of ventricular dilation due to hypertrophic cardiomyopathy. Quantitatively, the ejection fraction is considered higher than 70%.
A cardiac arrest attributed to ventricular tachycardia or ventricular fibrillation.
Cardiac arrest that was a result of bradycardia.
An anatomic deformity of the heart, ventricles or great vessels
An electrocardiographic finding of an atypical passage of electrical impulses through the cardiac ventricles. This includes fascicular blocks (hemiblocks), bundle branch blocks, non-specific conduction delays and ventricular pacing. (ACC)
Heart disease that is primarily due to a valvular defect or abnormality. Valve disease that is felt to be significant but does not fulfill the definition for primary valvular heat disease is considered contributory valvular heart disease.
A pathologic and/or clinical finding indicating the spread of a lymphomatous process to an anatomic site other than lymph nodes.
A rapidly disintegrating film-coated tablet composed of the fluoropyrimidine carbamate antimetabolite capecitabine with antineoplastic activity. As a prodrug, capecitabine is converted to 5'-deoxy-5-fluorocytidine (5'-DFCR) by hepatic carboxylesterase and then to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase and is eventually activated by thymidine phosphorylase to its cytotoxic moiety, 5-fluorouracil (5-FU); subsequently, 5-FU is metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits DNA synthesis and cell division by reducing normal thymidine triphosphate production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate for incorporation into the RNA strand. Capecitabine rapidly disintegrating tablet (RDT) contains the water insoluble, disintegrating agent crospovidone which very rapidly disperses and swells in water making this RDT easier to swallow than the traditional capecitabine tablet.
A radioimmunoconjugate consisting of the iodine I 124-radiolabeled murine IgG1 monoclonal antibody (MoAb) 8H9 directed against the cell surface glycoprotein CD276 (4Ig-B7-H3) with potential for radioimaging using positron emission tomography (PET). Through convection enhanced delivery, iodine I 124 monoclonal antibody 8H9 binds to the 4Ig domain of CD276, in turn CD276 expressing tumor cells may be visualized upon PET imaging of the iodine I 124 moiety. CD276, a tumor associated antigen and member of the B7 family of co-stimulatory proteins, suppresses natural killer (NK) cell and cytotoxic T-lymhocyte activation; it is expressed on the cell membranes of a wide variety of tumors of neuroectodermal, mesenchymal and epithelial origin and its expression is associated with increased aggressiveness, poor prognosis and resistance.
A decoction of rhubarb root (Da Huang) and licorice root (Gan Cao) used in Chinese Herbal Medicine. Upon ingestion, the rhubarb/licorice herbal supplement may help improve appetite.
A phospholipid ether analog labeled with iodine I 124, with a potential imaging property upon positron emission tomography (PET). Upon administration, iodine I 124 NM404 selectively accumulates in and retains within tumor cells for a prolonged period of time due to the decreased activity of a phospholipase D (PLD), most likely isoform 1 of PLD, in tumor cells compared to normal cells. As tumor cells are unable to metabolize and eliminate MN404, tumor cells can be visualized upon PET imaging. In addition, iodine I 124 NM404 may provide a more accurate image of the tumor than imaging with the current standard. PLD is an enzyme found in the cell membrane of normal cells that degrades phospholipids.
A phospholipid ether analog labeled with iodine I 131, with potential radiotherapeutic and radioimaging potential upon positron emission tomography (PET). Upon administration, iodine I 131 NM404 selectively accumulates in and retains within tumor cells for a prolonged period of time due to the decreased activity of a phospholipase D (PLD), most likely isoform 1 of PLD, in tumor cells compared to normal cells. As tumor cells are unable to metabolize and eliminate MN404, tumor cells can be visualized upon PET imaging. In addition, iodine I 131 NM404 selectively delivers a cytotoxic dose of iodine I 131 to the tumor cells. PLD is an enzyme found in the cell membrane of normal cells that degrades phospholipids.
A proprietary RNA interference construct consisting of bifunctional short hairpin RNAs (shRNA) against human stathmin 1 (STMN1) encapsulated in the cationic bilamellar invaginated vesicle lipoplex (LP) with potential antineoplastic activity. pbi-shRNA STMN1 LP contains 2 stem-loop structures encoded by a plasmid vector. Upon intratumoral administration, one shRNA unit with a perfectly matched sequence renders the suppression of STMN1 mRNA translation (mRNA sequestration and cleavage-independent degradation) while the other unit with an imperfectly matched sequence renders STMN1 mRNA degradation via RNase H-like cleavage (cleavage-dependent mRNA silencing). The suppression of STMN1 expression in tumor cells result in a reduction of tumor cell proliferation. STMN1, a ubiquitous cytosolic phosphoprotein and tubulin modulator that plays a key role in mitosis, is overexpressed in a variety of tumors and correlates with poor prognosis.
A monoclonal antibody against myostatin (MSTN) with potential anti-cachexia activity. Upon administration, anti-myostatin monoclonal antibody LY2495655 binds to and neutralizes the MSTN protein, thereby blocking the MSTN signalling pathway. This may help decrease muscle protein breakdown and muscle weakness and may attenuate cancer cachexia. MSTN, a member of the transforming growth factor-beta (TGF-beta) superfamily, is a negative regulator of muscle growth and development.
An orally available, hydrochloride salt form of radotinib, a second-generation tyrosine kinase inhibitor of Bcr-Abl fusion protein and the platelet-derived growth factor receptor (PDGFR), with potential antineoplastic activity. Upon administration, radotinib specifically inhibits the Bcr-Abl fusion protein, an abnormal enzyme expressed in Philadelphia chromosome positive chronic myeloid leukemia (CML) cells. In addition, this agent also inhibits PDGFR thereby blocking PDGFR-mediated signal transduction pathways. The inhibitory effect of radotinib on these specific tyrosine kinases may decrease cellular proliferation and inhibit angiogenesis. This agent has shown potent efficacy in CML cells that are resistant to the first-generation standard tyrosine kinase inhibitors, such as imatinib, nilotinib and dasatinib. PDGFR, upregulated in many tumor cell types, is a receptor tyrosine kinase essential to cell migration and the development of the microvasculature.
A dissection that impairs flow. This includes Type C (a persisting contrast medium extravasation) in the presence of ischemia, Type D (a spiral filling defect with delayed but complete distal flow), Type E (persistent filling defect with delayed antegrade flow) and Type F (filling defect with impaired flow and total occlusion).
A proprietary, oral suspension containing a combination of agents comprised of a nonsteroidal anti-inflammatory agent, an alkylating agent, a histamine H2 antagonist and a sulfonamide with potential anti-angiogenic and antineoplastic activities. Antiangiogenic drug combination TL-118 is administrated as a specific dosing regimen and may result in a synergistic effect and reduce angiogenesis and inhibit tumor cell proliferation.
A powder for an oral solution comprised of the hydrochloride salt of 5-aminolevulinic acid (ALA) with a potential application for photodynamic therapy. After oral administration, ALA is converted intracellularly into the photosensitizer protoporphyrin IX (PpIX). Upon exposure to light of appropriate wavelength (violet to blue range), excited PpIX emits a characteristic red fluorescence which could facilitate guided resection, and generates excited singlet oxygen molecules that could kill cells when appropriate laser dosage is applied. ALA is preferentially taken up by and accumulates in many types of cancer cells compared to normal, healthy cells. Consequently, cancer cells can be visualized and can be distinguished from normal, healthy cells.
A topical hydrophilic gel containing a recombinant form of the human Cu/Zn superoxide dismutase (SOD1), a cytoplasmic antioxidant enzyme, encapsulated in liposomes with potential anti-inflammatory and adjuvant activities. Upon application of liposome-encapsulated recombinant human Cu/Zn SOD as a thin film on the irradiated area, the recombinant SOD1 is released and scavenges free oxygen radicals, thereby protecting cells from oxidative stress. This may prevent radiation-induced dermatitis as well as other types of skin reactions.
A fully human monoclonal antibody directed against the human vascular endothelial growth factor C (VEGFC or Flt4 ligand) with potential antiangiogenic activity. Anti-VEGFC monoclonal antibody VGX-100 specifically binds to and inhibits VEGFC protein, thereby preventing its binding to VEGFR3 (FLT4) or VEGFR2 (KDR or FLK1). This may prevent VEGFC-mediated signaling and may lead to the inhibition of vascular and lymphatic endothelial cell proliferation. The inhibition of tumor angiogenesis and lymphangiogenesis may eventually decrease tumor cell proliferation and prevent metastasis. VEGFC is overexpressed in a variety of cancer cells, and is associated with increased invasiveness and decreased survival.
A suspension of erythrocytes encapsulating L-asparaginase with potential antineoplastic activity. Upon administration of erythrocyte-encapsulated L-asparaginase suspension, L-asparagine is hydrolyzed to L-aspartic acid and ammonia in plasma, thereby depleting tumor cells of asparagine. Due to low asparagine synthetase activity in tumor cells, de novo synthesis of asparagine is suppressed within tumor cells. Shortage of asparagine prevents synthesis of important proteins necessary for tumor cell growth. Encapsulation of asparaginase in erythrocytes decreases the immunogenicity of exogenous protein, enhances its circulation time and may limit toxicity.
The status of an individual who in all likelihood is not living, but has not been officially declared dead.
The status of an individual is officially declared not living by an authority.
Events pertaining to observations about implantable cardiac leads.
A preparation of non-interleukin-2 primed, tumor activated allogeneic natural killer (NK) cells with potential immunostimulating activity. The allogeneic NK cells obtained from a first or second degree relative of the patient are co-incubated with a lysate from the CTV-1 cell line, a minimally differentiated myeloid line derived from an acute myelogenous leukemia patient. Infusion of CNDO-109-activated allogeneic NK cells may be able to lyse and destroy NK-resistant tumor cells and a broad spectrum of tumor cells.
An oligoclonal therapeutic composed of three fully human monoclonal antibodies targeting epidermal growth factor receptor (EGFR or ErbB1), with potential antineoplastic activity. Upon administration of MM-151, the three antibodies bind to distinct, non-overlapping epitopes of EGFR, thereby preventing the binding of a full range of both high and low affinity EGFR ligands and inhibiting EGFR-ERK-mediated signaling. This eventually inhibits tumor cell proliferation in EGFR-overexpressing tumor cells. Furthermore, multi antibody-antigen bindings cause crosslinking of EGFR and downregulate receptor signalings that are mediated via heterodimerization of EGFR with other members of the EGFR family. EGFR, a receptor tyrosine kinase overexpressed in a variety of cancer cell types, is a key regulator of cancer cell proliferation, apoptosis, invasion, and metastasis.
A radioimmunoconjugate containing rituximab, a recombinant chimeric murine/human antibody directed against the human CD20 antigen, conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and labeled with the radioisotope copper Cu 64 with potential diagnostic properties upon positron emission tomography (PET) imaging. The monoclonal antibody moiety of copper Cu 64-DOTA-Rituximab specifically binds to cell surface antigen CD20. Upon binding, the radioisotope moiety may be detected using PET, thereby allowing the imaging and quantification of CD20-expressing tumor cells. CD20 is a non-glycosylated phosphoprotein that is exclusively expressed on B cells during most stages of B cell development and is often overexpressed in B-cell malignancies.
A cancer vaccine consisting of allogeneic, immortalized dendritic cells (DCs) loaded with tumor specific antigens and activated, with potential immunostimulatory and antineoplastic activities. Upon intratumoral administration of the allogeneic dendritic cell vaccine COMBIG-DC, these activated DCs attract natural killer (NK) cells, induce an anti-inflammatory response leading to the induction of NK-cell-mediated tumor cell death. Upon release of tumor associated antigens (TAAs) from the lysed tumor cells, these antigens are taken up by antigen presenting cells which activate the immune system to elicit a potent cytotoxic T-cell (CTL) response against the TAAs, resulting in the death of TAAs-expressing tumor cells.
A cancer vaccine based on virus-like replicon particles (VRP) packaged with an alphaviral vector encoding the extracellular domain (ECD) and transmembrane (TM) regions of the human epidermal growth factor receptor 2 (EGFR2, NEU or HER2), with potential antineoplastic activity. After immunization with HER2 ECD+TM virus-like replicon particles vaccine AVX901, the VRPs infect cells and express HER2 ECD+TM protein that may activate the immune system to elicit a cytotoxic T-lymphocyte (CTL) response against HER2-expressing tumor cells. The alphaviral replicon of this vaccine is an attenuated strain of the Venezuelan equine encephalitis virus (VEEV) in which 3 of the 7 viral genes were substituted with a truncated HER2 gene to create a self-amplifying replicon RNA. HER2, a tyrosine kinase involved in several cell growth signaling pathways, is dysregulated or overexpressed in a wide variety of cancer cell types.
The cardiac lead has been left in situ but is not in use. (ACC)
Sharp stabbing chest pain or reproduction of pain on palpation. Less common isolated presentations, primarily in older adults, include nausea and vomiting, diaphoresis, and unexplained fatigue. J Am Coll Cardiol, 2007; 50:1-157, doi:10.1016/j. jacc.2007.02.013 (Published online 6 August 2007). (ACC)
Cardiac arrest which occurs before a percutaneous coronary intervention can take place. (ACC)
A cardiac lead requires revision, at which time the generator to the device will be replaced. (ACC)
A cardiac lead has damaged local tissue enough to require treatment. (ACC)
Insulation failure manifests as low lead impedance either absolutely (below manufacturer's product specifications) or by a significant decrease from previously stable chronic values. (ACC)
The coronary sinus / left ventricular lead was not implanted because the lead position resulted in undesirable stimulation of the diaphragm. (ACC)
A longstanding, complete blockage of a vessel. (ACC)
The right coronary artery supplies the posterior descending artery (PDA) and the circumflex supplies the posterolateral artery (PLA). Thus, there is approximately equal contribution to the inferior surface of the left ventricle from both the left circumflex and right coronary arteries. (ACC)
The posterior descending artery (PDA) and posterolateral artery (PLA) arises from the right coronary artery. (ACC)
The patient died while in a medical center such as a hospital, skilled nursing facility (SNF), intermediate care facility (ICF), or a freestanding hospice center. (ACC)
Access to the subject's vasculature is troublesome or formidable. (ACC)
Placement of intracoronary devices across the coronary stenosis is troublesome or formidable. (ACC)
The cardiac lead has been removed from the body. (ACC)
Mechanical Circulatory Support was inserted during a non-Percutaneous Coronary Intervention (PCI) procedure. (ACC)
Mechanical Circulatory Support was inserted during the procedure. (ACC)
Mechanical Circulatory Support was inserted during the procedure after Percutaneous Coronary Intervention (PCI) started. (ACC)
The diameter across the left atrium measured at the end of systole. (ACC)
The posterior descending artery (PDA) and posterolateral artery (PLA) arises from the left circumflex artery. (ACC)
The diameter across the ventricle at the end of diastole, excluding the thickness of the walls. (ACC)
The diameter across the ventricle at the end of systole, excluding the thickness of the walls. (ACC)
Mechanical Circulatory Support was in place at the start of the procedure. (ACC)
The medical condition or the procedure affects the device implantation site. (ACC)
An intended medical or surgical procedure necessitates the relocation of a cardiac lead. (ACC)
Evidence of mild retrograde blood flow through the valve(s) of the heart. (ACC)
The cardiac valve orifice is abnormally narrow, to a mild degree. (ACC)
Evidence of moderate retrograde blood flow through the valve(s) of the heart. (ACC)
The cardiac valve orifice is abnormally narrow, to a moderate degree. (ACC)
No evidence of any retrograde blood flow through the valve(s) in the heart. (ACC)
The cardiac valve orifice is not abnormally narrow. (ACC)
There was less than 50% stenosis (reduction in cross-sectional area) in all coronary artery branches. (ACC)
There was greater than or equal to 50% stenosis (reduction in cross-sectional area) in one coronary artery. (ACC)
A non-neoplastic or neoplastic disorder that affects the intrahepatic or extrahepatic bile ducts or the gallbladder. Representative examples of non-neoplastic disorders include cholangitis and cholecystitis. Representative examples of neoplastic disorders include extrahepatic bile duct adenoma, intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder carcinoma.
A non-neoplastic disorder that affects the intrahepatic or extrahepatic bile ducts. Representative examples include cholangitis and biliary atresia.
A morphologic finding indicating the presence of single or multiple foci of hepatocytes that exhibit dysplastic changes. These microscopic foci measure less than 1 mm in diameter and are usually detected in cirrhotic livers.
An adenoma that arises from the intrahepatic bile ducts and it is characterized by the presence of microcystic changes.
Reduced ability to walk in a straight line while placing the feet heal to toe. []
An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm.
XMEN is an X-linked immunodeficiency characterized by CD4 (186940) lymphopenia, severe chronic viral infections, and defective T-lymphocyte activation (Li et al., 2011).
Xp11 translocation renal cell carcinomas (RCCX1) are a group of neoplasms distinguished by chromosomal translocations with breakpoints involving the TFE3 gene within tumor cells. The result is a TFE3 transcription factor gene fusion with 1 of multiple reported genes including ASPRCR1 (606236) on chromosome 17q25 and PRCC (179755) on 1q21, and more rarely, NONO (300084) on Xq13, SFPQ (605199) on 1p34, CLTC (118955) on 17q23, and unknown genes on chromosomes 3 and 10. Xp11 translocations are often found in pediatric tumors and less commonly in adults. However, adult cases may outnumber pediatric cases since renal cell carcinoma is more common in the adult population. Prior chemotherapy is a known risk factor for Xp11 translocations. Histology shows both clear cells and papillary architecture, often with abundant psammoma bodies, although variable histologic features have been observed (review by Ross and Argani, 2010). For a discussion of genetic heterogeneity of renal cell carcinoma, see RCC (144700).
Ogden syndrome is an X-linked neurodevelopmental disorder characterized by postnatal growth failure, severely delayed psychomotor development, variable dysmorphic features, and hypotonia. Most patients also have cardiac malformations or arrhythmias (summary by Popp et al., 2015).
The Nascimento type of X-linked syndromic mental retardation is characterized by dysmorphic features, including large head, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, large ears, wide mouth, myxedematous appearance, hirsutism, abnormal hair whorls, micropenis, and onychodystrophy. Female carriers have normal cognition, but may show subtle facial features (summary by Budny et al., 2010).
Kabuki syndrome (KS) is characterized by typical facial features (long palpebral fissures with eversion of the lateral third of the lower eyelid; arched and broad eyebrows; short columella with depressed nasal tip; large, prominent, or cupped ears), minor skeletal anomalies, persistence of fetal fingertip pads, mild-to-moderate intellectual disability, and postnatal growth deficiency. Other findings may include: congenital heart defects; genitourinary anomalies; cleft lip and/or palate; gastrointestinal anomalies including anal atresia, ptosis, and strabismus; and widely spaced teeth and hypodontia. Functional differences can include: increased susceptibility to infections and autoimmune disorders, seizures, endocrinologic abnormalities (including isolated premature thelarche in females), feeding problems, and hearing loss.
Multiple congenital anomalies-hypotonia-seizures syndrome-2 is an X-linked recessive neurodevelopmental disorder characterized by dysmorphic features, neonatal hypotonia, myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Some affected individuals die in infancy (summary by Johnston et al., 2012). The phenotype shows clinical variability with regard to severity and extraneurologic features. However, most patients present in infancy with early-onset epileptic encephalopathy associated with developmental arrest and subsequent severe neurologic disability (summary by Belet et al., 2014, Kato et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080); for a discussion of genetic heterogeneity of EIEE, see 308350; and for a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Chromosome Xq27.3-q28 duplication syndrome is an X-linked recessive neurodevelopmental disorder characterized by mild mental retardation, mild facial dysmorphism, short stature, and primary testicular failure manifest as high-pitched voice, sparse body hair, abdominal obesity, and small testes. Female carriers may have short stature and premature ovarian failure (summary by Rio et al., 2010).
Congenital absence of the nails is a rare condition. Some pedigrees display complete congenital absence of the nails (see, e.g., NDNC4, 206800), whereas in other pedigrees there is only partial congenital anonychia, with the thumbs and great toes most severely affected and progressively less severe changes in the more lateral digits (summary by Charteris, 1918). This form of nail disorder is referred to here as nonsyndromic congenital nail disorder-6 (NDNC6). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
Atrophy of the capillary lamina of choroid.
Complete bilateral fractures of the pars interarticularis resulting in the anterior slippage of the fifth lumbar vertebral body (L5) onto the sacrum (level S1).
An increase in amplitude of waves returned in ultrasonography of the kidney, which is generally displayed as increased brightness of the signal.
A rare balance disorder with characteristic of auditory and/or vestibular symptoms. This condition is caused by an opening (dehiscence) in the bone that overlays the superior semicircular canal within the inner ear.
The Mardini-Nyhan association comprises uni- or bilateral lung agenesis, complex cardiac defects, particularly total anomalous pulmonary venous return (TAPVR), and thumb abnormalities (summary by Hastings et al., 2009).
Underdevelopment of the areola, the circular area of pigmented skin surrounding the nipple.
Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD above the mean. Alternatively, an apparently increased distance between the hairline and the glabella.
Generalized arterial calcification of infancy (GACI) is characterized by infantile onset of widespread arterial calcification and/or narrowing of large- and medium-sized vessels resulting in cardiovascular findings (which can include heart failure, respiratory distress, edema, cyanosis, hypertension, and/or cardiomegaly). Additional findings can include extravascular calcifications (particularly periarticular), typical skin and retinal manifestations of pseudoxanthoma elasticum (PXE), hearing loss, and development of rickets after infancy. While mortality in infancy is high, survival into the second and third decade has been reported.
Acrodysostosis-1 is a form of skeletal dysplasia characterized by short stature, severe brachydactyly, facial dysostosis, and nasal hypoplasia. Affected individuals often have advanced bone age and obesity. Laboratory studies show resistance to multiple hormones, including parathyroid, thyrotropin, calcitonin, growth hormone-releasing hormone, and gonadotropin (summary by Linglart et al., 2011). However, not all patients show endocrine abnormalities (Lee et al., 2012). Genetic Heterogeneity of Acrodysostosis See also ACRDYS2 (614613), caused by mutation in the PDE4D gene (600129) on chromosome 5q12.
A distinct group of inborn defects of complex V (ATP synthase) is represented by the enzyme deficiency due to nuclear genome mutations characterized by a selective inhibition of ATP synthase biogenesis. Biochemically, the patients show a generalized decrease in the content of ATP synthase complex which is less than 30% of normal. Most cases present with neonatal-onset hypotonia, lactic acidosis, hyperammonemia, hypertrophic cardiomyopathy, and 3-methylglutaconic aciduria. Many patients die within a few months or years (summary by Mayr et al., 2010). Genetic Heterogeneity of Mitochondrial Complex V Deficiency Other nuclear types of mitochondrial complex V deficiency include MC5DN2 (614052), caused by mutation in the TMEM70 gene (612418) on chromosome 8q21; MC5DN3 (614053), caused by mutation in the ATP5E gene (ATP5F1E; 606153) on chromosome 20q13; MC5DN4 (615228), caused by mutation in the ATP5A1 gene (ATP5FA1; 164360) on chromosome 18q; and MC5DN5 (618120), caused by mutation in the ATP5D gene (ATP5F1D; 603150) on chromosome 19p13. Mutations in the mitochondrial-encoded MTATP6 (516060) and MTATP8 (516070) genes can also cause mitochondrial complex V deficiency (see, e.g., 500015).
A small V-shaped indentation on the internal aspect of the femoral head. This feature is well illustrated in Figure 5 of PMID:11694546.
Presence of an angular or V -shaped indentation on the ulnar side of the fifth metacarpal bone (i.e., on the sides towards the fifth finger).
Multiple mitochondrial dysfunctions syndrome is a severe autosomal recessive disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, and early death (summary by Seyda et al., 2001). Genetic Heterogeneity of Multiple Mitochondrial Dysfunctions Syndrome See also MMDS2 (614299), caused by mutation in the BOLA3 gene (613183) on chromosome 2p13; MMDS3 (615330), caused by mutation in the IBA57 gene (615316) on chromosome 1q42; MMDS4 (616370), caused by mutation in the ISCA2 gene (615317) on chromosome 14q24; MMDS5 (617613), caused by mutation in the ISCA1 gene (611006) on chromosome 9q21; and MMDS6 (617954), caused by mutation in the PMPCB gene (603131) on chromosome 7q22.
FBLN5 -related cutis laxa is characterized by cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonary artery stenosis, and other evidence of a generalized connective disorder such as inguinal hernias and hollow viscus diverticula (e.g., intestine, bladder). Occasionally, supravalvular aortic stenosis is observed. Intrafamilial variability in age of onset is observed. Cardiorespiratory failure from complications of pulmonary emphysema (respiratory or cardiac insufficiency) is the most common cause of death.
Syndromic optic atrophy, also known as DOA+ syndrome, is a neurologic disorder characterized most commonly by an insidious onset of visual loss and sensorineural hearing loss in childhood with variable presentation of other clinical manifestations including progressive external ophthalmoplegia (PEO), muscle cramps, hyperreflexia, and ataxia. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010).
An abnormality of the development of the toenails.
Small fiber neuropathy is a condition characterized by severe pain attacks that typically begin in the feet or hands. As a person ages, the pain attacks can affect other regions. Some people initially experience a more generalized, whole-body pain. The attacks usually consist of pain described as stabbing or burning, or abnormal skin sensations such as tingling or itchiness. In some individuals, the pain is more severe during times of rest or at night. The signs and symptoms of small fiber neuropathy usually begin in adolescence to mid-adulthood.Individuals with small fiber neuropathy cannot feel pain that is concentrated in a very small area, such as the prick of a pin. However, they have an increased sensitivity to pain in general (hyperalgesia) and experience pain from stimulation that typically does not cause pain (hypoesthesia). People affected with this condition may also have a reduced ability to differentiate between hot and cold. However, in some individuals, the pain attacks are provoked by cold or warm triggers.Some affected individuals have urinary or bowel problems, episodes of rapid heartbeat (palpitations), dry eyes or mouth, or abnormal sweating. They can also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting.Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.
Duplication of the fibula. This may occur as a part of diplopodia (accessory tarsal or metatarsal bone). Diplopodia with double fibula is an extremely rare condition.
Reduction in thickness of the basal lamina of the glomerulus of the kidney.
An eyebrow that extends straight across the brow, without curve.
Cataract in both eyes that are present at birth.
The presence of a tail-like skin appendage located adjacent to the sacrum.
An anomalous radiographic appearance of the developing pelvis, in which the greater ischiadic noth (incisura ischiadica major) is shallow and the pelvis takes on the appearance said to resemble a halberd (a weapon especially of the 15th and 16th centuries consisting typically of a battle-ax and pike mounted on a handle).
Decreased intensity of the patellar reflex (also known as the knee jerk reflex).
An abnormal predominance of type II muscle fibers (in general, this feature can only be observed on muscle biopsy).
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus. []
Carbamazepine is an aromatic anticonvulsant used to treat epilepsy and other seizure disorders, as well as bipolar disorder and trigeminal neuralgia. Carbamazepine can cause a variety of cutaneous adverse reactions, ranging from mild maculopapular eruptions to Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The genetic variant HLA-B*15:02 is associated with the risk of SJS/TEN. Patients who have at least one copy of the HLA-B*15:02 allele (considered HLA-B*15:02-positive) have a significantly increased risk for SJS/TEN compared to non-carriers, and it is recommended that they receive an alternate drug. It is important to note that it is possible for a patient without HLA-B*15:02 to develop SJS/TEN. Guidelines regarding the use of pharmacogenomic tests in dosing for carbamazepine have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA448785).
Eyelid partly covered by skin when eyes are open.
The presence of multiple deletions of mitochondrial DNA (mtDNA).
An unusually severe viral infection. [PMID:21960712]
Presence of multiple dilatations (sac-like outpouchings) in the blood vessels of the conjunctiva.
Thrombocythemia, or thrombocytosis, is a myeloproliferative disorder characterized by excessive platelet production resulting in increased numbers of circulating platelets. Thrombocythemia can be associated with thrombotic or hemorrhagic episodes and occasional leukemic transformation (summary by Wiestner et al., 1998). Genetic Heterogeneity of Thrombocythemia THCYT2 (601977) is caused by germline or somatic mutation in the THPO receptor gene (MPL; 159530) on chromosome 1p34; THCYT3 (614521) is caused by germline or somatic mutation in the JAK2 gene (147796) on chromosome 9p; and a possible X-linked form (THCYTX; 300331) has been reported. Somatic mutations in the TET2 (612839), ASXL1 (612990), SH2B3 (605093), and SF3B1 (605590) genes have also been found in cases of essential thrombocythemia. Somatic mutation in the CALR gene (109091) occurs in approximately 70% of essential thrombocythemia patients who lack JAK2 and MPL mutations (Klampfl et al., 2013; Nangalia et al., 2013).
A reduction of previously attained ability to see.
Vitiligo is a condition that causes patchy loss of skin coloring (pigmentation). The average age of onset of vitiligo is in the mid-twenties, but it can appear at any age. It tends to progress over time, with larger areas of the skin losing pigment. Some people with vitiligo also have patches of pigment loss affecting the hair on their scalp or body.Researchers have identified several forms of vitiligo. Generalized vitiligo (also called nonsegmental vitiligo), which is the most common form, involves loss of pigment (depigmentation) in patches of skin all over the body. Depigmentation typically occurs on the face, neck, and scalp, and around body openings such as the mouth and genitals. Sometimes pigment is lost in mucous membranes, such as the lips. Loss of pigmentation is also frequently seen in areas that tend to experience rubbing, impact, or other trauma, such as the hands, arms, and places where bones are close to the skin surface (bony prominences). Another form called segmental vitiligo is associated with smaller patches of depigmented skin that appear on one side of the body in a limited area; this occurs in about 10 percent of affected individuals.Vitiligo is generally considered to be an autoimmune disorder. Autoimmune disorders occur when the immune system attacks the body's own tissues and organs. In people with vitiligo the immune system appears to attack the pigment cells (melanocytes) in the skin. About 15 to 25 percent of people with vitiligo are also affected by at least one other autoimmune disorder, particularly autoimmune thyroid disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, Addison disease, or systemic lupus erythematosus.In the absence of other autoimmune conditions, vitiligo does not affect general health or physical functioning. However, concerns about appearance and ethnic identity are significant issues for many affected individuals.
Absence of the middle phalanx of the little (5th) finger.
Congenital anonychia is defined as the absence of fingernails and toenails. Anonychia and its milder phenotypic variant, hyponychia, usually occur as a feature of genetic syndromes, in association with significant skeletal and limb anomalies. Isolated nonsyndromic congenital anonychia/hyponychia is a rare entity that usually follows autosomal recessive inheritance with variable expression, even within a given family. The nail phenotypes observed range from no nail field to a nail field of reduced size with an absent or rudimentary nail (summary by Bruchle et al., 2008). This form of nail disorder is referred to here as nonsyndromic congenital nail disorder-4 (NDNC4). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
Generalized excessive, abnormal hairiness.
Failure of formation of the lumen of the gallbladder, often associated with gallbladder hypoplasia.
An abnormally increased size of the cerebellum compared to other brain structures.
Fibrochondrogenesis is a severe, autosomal recessive, short-limbed skeletal dysplasia clinically characterized by a flat midface with a small nose and anteverted nares, significant shortening of all limb segments but relatively normal hands and feet, and a small bell-shaped thorax with a protuberant abdomen. Radiographically, the long bones are short and have broad metaphyseal ends, giving them a dumb-bell shape. The vertebral bodies are flat and, on lateral view, have a distinctive pinched appearance, with a hypoplastic posterior end and a rounded anterior end. The ribs are typically short and wide and have metaphyseal cupping at both ends (summary by Tompson et al., 2010). Genetic Heterogeneity of Fibrochondrogenesis Fibrochondrogenesis-2 (FBCG2; 614524) is caused by mutation in the COL11A2 gene (120290) on chromosome 6p21.3.
Geleophysic dysplasia, a progressive condition resembling a lysosomal storage disorder, is characterized by short stature, short hands and feet, progressive joint limitation and contractures, distinctive facial features, progressive cardiac valvular disease, and thickened skin. Intellect is normal. Major findings are likely to be present in the first year of life. Cardiac, respiratory, and lung involvement result in death before age five years in approximately 33% of individuals with ADAMTSL2-related geleophysic dysplasia.
Heterozygous protein S deficiency, like protein C deficiency (176860), is characterized by recurrent venous thrombosis. Bertina (1990) classified protein S deficiency into 3 clinical subtypes based on laboratory findings. Type I refers to deficiency of both free and total protein S as well as decreased protein S activity; type II shows normal plasma values, but decreased protein S activity; and type III shows decreased free protein S levels and activity, but normal total protein S levels. Approximately 40% of protein S circulates as a free active form, whereas the remaining 60% circulates as an inactive form bound to C4BPA (120830). Zoller et al. (1995) observed coexistence of type I and type III PROS1-deficient phenotypes within a single family and determined that the subtypes are allelic. Under normal conditions, the concentration of protein S exceeds that of C4BPA by approximately 30 to 40%. Thus, free protein S is the molar surplus of protein S over C4BPA. Mild protein S deficiency will thus present with selective deficiency of free protein S, whereas more pronounced protein S deficiency will also decrease the complexed protein S and consequently the total protein S level. These findings explained why assays for free protein S have a higher predictive value for protein S deficiency. See also autosomal recessive thrombophilia due to protein S deficiency (THPH6; 614514), which is a more severe disorder.
An autosomal recessive disorder caused by mutation of the AK1 gene. It is associated with moderate to severe non-spherocytic hemolytic anemia and, in some cases, with intellectual disability and psychomotor impairment.
Presence of abnormal additional layers of the basement membrane of the glomerulus.
The presence of developmental dysplasia of the cerebellum.
Microcephaly and chorioretinopathy is an autosomal recessive developmental disorder characterized by delayed psychomotor development and visual impairment, often accompanied by short stature (summary by Martin et al., 2014). Genetic Heterogeneity of Microcephaly and Chorioretinopathy See also MCCRP2 (616171), caused by mutation in the PLK4 gene (605031) on chromosome 4q27, and MCCRP3 (616335), caused by mutation in the TUBGCP4 gene (609610) on chromosome 15q15. An autosomal dominant form of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation is caused by heterozygous mutation in the KIF11 gene (148760) on chromosome 10q23. See also Mirhosseini-Holmes-Walton syndrome (autosomal recessive pigmentary retinopathy and mental retardation; 268050), which has been mapped to chromosome 8q21.3-q22.1.
A developmental defect leading to the union of two adjacent vertebrae. [HPO:probinson]
Formation of crystals owing to an increased concentration of orotic acid in the urine.
Acute infantile liver failure resulting from TRMU mutation is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development (Zeharia et al., 2009). See also transient infantile mitochondrial myopathy (MMIT; 500009), which is a similar disorder. A more severe, permanent disorder with some overlapping features is associated with mitochondrial DNA depletion (251880). See ILFS1 (615438) for information on syndromic infantile liver failure.
Absent thumb, i.e., the absence of both phalanges of a thumb and the associated soft tissues.
Gallstones composed primarily of bilirubin and calcium salts (calcium bilirubinate) with a low cholesterol concentration.
An increase in size of the ventricular system of the brain.
Underdevelopment of the vertebral artery on one side.
Abnormal tortuous (i.e., twisted) form of arteries.
An electrocardiographic finding of an abnormality of T wave duration or morphology or of early repolarization. (CDISC)
Progressively worsening joint contractures.
Underdevelopment of the abdominal musculature.
Repeated episodes of abortion (Expulsion of the product of fertilization before completing the term of gestation) without deliberate interference.
Hypotrichosis simplex refers to a group of hereditary isolated alopecias characterized by diffuse and progressive hair loss, usually beginning in early childhood (Pasternack et al., 2008). Localized autosomal recessive hypotrichosis (LAH) is characterized by fragile hairs that break easily, leaving short, sparse scalp hairs. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas (summary by Schaffer et al., 2006). Woolly hair (WH) refers to a group of hair shaft disorders that are characterized by fine and tightly curled hair. Compared to normal curly hair that is observed in some populations, WH grows slowly and stops growing after a few inches. Under light microscopy, WH shows some structural anomalies, including trichorrhexis nodosa and tapered ends (summary by Petukhova et al., 2009). Several families have been reported in which some affected individuals exhibit features of hypotrichosis and others have woolly scalp hair (Khan et al., 2011). Woolly hair is also a feature of several syndromes, such as Naxos disease (601214) and cardiofaciocutaneous syndrome (115150) (Petukhova et al., 2009), or the palmoplantar keratoderma and cardiomyopathy syndrome (601214) (Carvajal-Huerta, 1998). Genetic Heterogeneity of Hypotrichosis and Woolly Hair For a discussion of genetic heterogeneity of nonsyndromic hypotrichosis, see HYPT1 (605389). For a discussion of genetic heterogeneity of localized hypotrichosis, see LAH1 (HYPT6; 607903). Another form of autosomal recessive woolly hair with or without hypotrichosis (ARWH2; 604379) is caused by mutation in the LIPH gene (607365) and is allelic to autosomal recessive localized hypotrichosis (LAH2). ARWH3 (616760) is caused by mutation in the KRT25 gene (616646) on chromosome 17q21. An autosomal dominant form of woolly hair with hypotrichosis (HYPT13; 615896) is caused by mutation in the KRT71 gene (608245) on chromosome 12q13. Another autosomal dominant form of woolly hair (ADWH; 194300) with normal hair density is caused by mutation in the KRT74 gene (608248) on chromosome 12q13, and is allelic to an autosomal dominant form of hypotrichosis simplex of the scalp (HYPT3; 613981) as well as an ectodermal dysplasia of the hair/nail type (ECTD7; 614929).
Hypergranulosis is an increased thickness of the stratum granulosum.
A type of low sperm count where ejaculated semen contains less than 100,000 spermatozoa per ml. With cryptozoospermia, the sperm count may fluctuate and a zero sperm count in the ejaculate may be initially measured. If sperm are observed in a second semen sample following centrifugation, the diagnosis of cryptozoospermia can be made (and azoospermia can be ruled out).
Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. Osteogenesis imperfecta type VI is a severe autosomal recessive form of the disorder (Glorieux et al., 2002; Becker et al., 2011).
An abnormal anatomical location of the posterior lobe of the hypophysis, also known as the neurohypophysis. The posterior pituitary is normally present in the dorsal portion of the sella turcica, but when ectopic is usually near the median eminence. This defect is likely to be due to abnormal migration during embryogenesis.
Susceptibility to platelet-type bleeding disorder-13 is due to a defective thromboxane A2 receptor on platelets. The susceptibility is inherited in an autosomal dominant pattern, but clinical features, including mild mucocutaneous bleeding, occur only in the presence of a 'second hit' affecting platelet function; this second hit may be either in the TBXA2R gene or in another gene affecting the coagulation cascade (summary by Mumford et al., 2010).
Progressive myoclonic epilepsy-6 is an autosomal recessive neurologic disorder characterized by onset of ataxia in the first years of life, followed by action myoclonus and seizures later in childhood, and loss of independent ambulation in the second decade. Cognition is not usually affected, although mild memory difficulties may occur in the third decade (summary by Corbett et al., 2011). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
An extremely rare fatal neurometabolic developmental disorder with clinical characteristics of muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly.
An excessive number of small gyri (convolutions) on the surface of the brain in the frontoparietal region.
An excessive number of small gyri (convolutions) on the surface of the brain in the region surrounding the sylvian fissures.
Moyamoya disease is a cerebrovascular disorder caused by stenotic changes of terminal portions of the internal carotid arteries accompanied by surrounding fine arterial collateral vessels. These vascular networks resemble a 'puff of smoke' (Japanese: moyamoya) in angiographic imaging (summary by Roder et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of moyamoya disease, see MYMY1 (252350).
Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997). For a discussion of genetic heterogeneity of familial atrial fibrillation, see ATFB1 (608583).
Mitochondrial complex V deficiency is a shortage (deficiency) of a protein complex called complex V or a loss of its function. Complex V is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex V is the last of five mitochondrial complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy.Mitochondrial complex V deficiency can cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system and the heart. The disorder can be life-threatening in infancy or early childhood. Affected individuals may have feeding problems, slow growth, low muscle tone (hypotonia), extreme fatigue (lethargy), and developmental delay. They tend to develop elevated levels of lactic acid in the blood (lactic acidosis), which can cause nausea, vomiting, weakness, and rapid breathing. High levels of ammonia in the blood (hyperammonemia) can also occur in affected individuals, and in some cases result in abnormal brain function (encephalopathy) and damage to other organs.Another common feature of mitochondrial complex V deficiency is hypertrophic cardiomyopathy. This condition is characterized by thickening (hypertrophy) of the heart (cardiac) muscle that can lead to heart failure. People with mitochondrial complex V deficiency may also have a characteristic pattern of facial features, including a high forehead, curved eyebrows, outside corners of the eyes that point downward (downslanting palpebral fissures), a prominent bridge of the nose, low-set ears, thin lips, and a small chin (micrognathia).Some people with mitochondrial complex V deficiency have groups of signs and symptoms that are classified as a specific syndrome. For example, mitochondrial complex V deficiency can cause a condition called neuropathy, ataxia, and retinitis pigmentosa (NARP). NARP causes a variety of signs and symptoms chiefly affecting the nervous system. Beginning in childhood or early adulthood, most people with NARP experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); muscle weakness; and problems with balance and coordination (ataxia). Many affected individuals also have cognitive impairment and an eye disorder called retinitis pigmentosa that causes vision loss.A condition called Leigh syndrome can also be caused by mitochondrial complex V deficiency. Leigh syndrome is characterized by progressive loss of mental and movement abilities (developmental or psychomotor regression) and typically results in death within 2 to 3 years after the onset of symptoms. Both NARP and Leigh syndrome can also have other causes.
Williams distal myopathy is an autosomal dominant slowly progressive muscular disorder characterized by distal muscle weakness and atrophy affecting the upper and lower limbs. Onset occurs around the third to fourth decades of life, and patients remain ambulatory even after long disease duration. Muscle biopsy shows nonspecific changes with no evidence of rods, necrosis, or inflammation (summary by Duff et al., 2011). Mutation in the FLNC gene can also cause myofibrillar myopathy-5 (MFM5; 609524), which shows a different pattern of muscle involvement and different histologic changes.
Reduced ability to flex the femur, that is, to pull the knee upward.
Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disorder characterized by facial dysmorphism, immunoglobulin deficiency resulting in recurrent infections, and mental retardation. Laboratory studies of patient cells show hypomethylation of satellite regions of chromosomes 1, 9, and 16, as well as pericentromeric chromosomal instability in response to phytohemagglutinin stimulation (summary by de Greef et al., 2011). For a discussion of genetic heterogeneity of immunodeficiency-centromeric instability-facial anomalies syndrome, see ICF1 (242860).
Aspergillus species are ubiquitous in nature and cause a wide spectrum of diseases, including saprophytic colonization of existing cavities (aspergilloma), allergic asthma, hypersensitivity pneumonitis, allergic bronchopulmonary aspergillosis, and disseminated disease associated with high mortality rates in patients with hematologic malignancies and recipients of solid organs and stem cell transplantations. Immunocompetent and nonatopic individuals are relatively resistant to infection, and disease occurs in the setting of host damage. Association of persistent inflammation with intractable infection is common in nonneutropenic patients after hematopoietic stem cell transplantation, as well as in allergic fungal diseases. The pathophysiology underlying Aspergillus infection highlights the bipolar nature of the inflammatory process in infection, in which early inflammation prevents or limits infection, but an uncontrolled response may oppose disease eradication (summary by Cunha et al., 2010). For information on familial occurrence of allergic bronchopulmonary aspergillosis, see 103920.
Multiple congenital anomalies-hypotonia-seizures syndrome is an autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary, and gastrointestinal systems. Most affected individuals die before 3 years of age (summary by Maydan et al., 2011). The disorder is caused by a defect in glycosylphosphatidylinositol biosynthesis; see GPIBD1 (610293). Genetic Heterogeneity of Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome MCAHS2 (300868) is caused by mutation in the PIGA gene (311770) on chromosome Xp22, and MCAHS3 (615398) is caused by mutation in the PIGT gene (610272) on chromosome 20q13. Knaus et al. (2018) provided a review of the main clinical features of the different types of MCAHS, noting that patients with mutations in the PIGN, PIGA, and PIGT genes have distinct patterns of facial anomalies that can be detected by computer-assisted comparison. Some individuals with MCAHS may have variable increases in alkaline phosphatase (AP) as well as variable decreases in GPI-linked proteins that can be detected by flow cytometry. However, there was no clear correlation between AP levels or GPI-linked protein abnormalities and degree of neurologic involvement, mutation class, or gene involved. Knaus et al. (2018) concluded that a distinction between MCAHS and HPMRS1 (239300), which is also caused by mutation in genes involved in GPI biosynthesis, may be artificial and even inaccurate, and that all these disorders should be considered and classified together under the more encompassing term of 'GPI biosynthesis defects' (GPIBD).
Anhaptoglobinemia refers to absence of the serum glycoprotein haptoglobin, a hemoglobin-binding acute-phase protein (summary by Teye et al., 2004). Serum levels of haptoglobin vary among normal persons: levels are low in the neonatal period and in the elderly, differ by population, and can be influenced by environmental factors, such as infection. Secondary hypohaptoglobinemia can occur as a consequence of hemolysis, during which haptoglobin binds to free hemoglobin (summary by Delanghe et al., 1998).
Sick sinus syndrome may be encountered at any age but is primarily a disease of the elderly and is often secondary to other cardiac disorders when diagnosed in younger individuals. Symptoms are often intermittent and/or nonspecific and include dizziness, syncope, and heart failure. The only effective treatment for symptomatic and irreversible sinus node dysfunction is permanent cardiac pacing, and sick sinus syndrome remains the most common indication for permanent pacemaker implantation (summary by Holm et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of sick sinus syndrome, see SSS1 (608567).
COXPD8 is an autosomal recessive disorder due to dysfunction of the mitochondrial respiratory chain. The main clinical manifestation is a lethal infantile hypertrophic cardiomyopathy, but there may also be subtle skeletal muscle and brain involvement. Biochemical studies show combined respiratory chain complex deficiencies in complexes I, III, and IV in cardiac muscle, skeletal muscle, and brain. The liver is not affected (summary by Gotz et al., 2011). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Keppen-Lubinsky syndrome is a very rare disorder characterized by severely delayed psychomotor development, hypertonia, hyperreflexia, generalized lipodystrophy giving an aged appearance, and distinctive dysmorphic features, including microcephaly, prominent eyes, narrow nasal bridge, and open mouth (summary by Masotti et al., 2015).
DYRK1A-related intellectual disability syndrome is characterized by intellectual disability including impaired speech development, autism spectrum disorder including anxious and/or stereotypic behavior problems, and microcephaly. Affected individuals often have a clinically recognizable phenotype including a typical facial gestalt, feeding problems, seizures, hypertonia, gait disturbances, and foot anomalies. The majority of affected individuals function in the moderate to severe range of intellectual disability; however, a few individuals with mild intellectual disability have been reported. About half of affected individuals develop epilepsy including atonic attacks, absences, and generalized myoclonic seizures. About half of affected individuals develop scoliosis, kyphosis, and/or pectus excavatum. About one third have short stature. Rarely, endocrine problems and dental, ophthalmologic, and/or cardiac anomalies are reported.
Methylmalonate semialdehyde dehydrogenase deficiency is a rare autosomal recessive inborn error of metabolism with a highly variable phenotype. Some patients may be asymptomatic, whereas others show global developmental delay, nonspecific dysmorphic features, and delayed myelination on brain imaging. Laboratory studies typically show increased urinary 3-hydroxyisobutyric acid, although additional metabolic abnormalities may also be observed (summary by Marcadier et al., 2013).
Mosaic variegated aneuploidy syndrome is an autosomal recessive disorder characterized by poor growth and variable phenotypic manifestations, such as facial dysmorphism and congenital heart defects, associated with mosaic aneuploidies resulting from defects in cell division (summary by Snape et al., 2011). See also MVA1 (257300), caused by mutation in the BUB1B gene (602860) on chromosome 15q15.
Occipital cortical malformations (OCCM) is an autosomal recessive condition in which affected individuals develop seizures, sometimes associated with transient visual changes. Brain MRI shows both pachygyria and polymicrogyria restricted to the lateral occipital lobes (summary by Barak et al., 2011).
DNMT1-related disorder is a degenerative disorder of the central and peripheral nervous systems comprising a phenotypic spectrum that includes hereditary sensory and autonomic neuropathy type 1E (HSAN1E) and autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN). DNMT1 disorder is often characterized by moderate-to-severe sensorineural hearing loss beginning in the teens or early 20s, sensory impairment, sudomotor dysfunction (loss of sweating), and dementia usually beginning in the mid-40s. In some affected individuals, narcolepsy/cataplexy syndrome and ataxia are predominant findings.
Hydrolethalus syndrome is an autosomal recessive embryonic lethal disorder characterized by hydrocephaly or anencephaly, postaxial polydactyly of the upper limbs, and pre- or postaxial polydactyly of the lower limbs. Duplication of the hallux is a common finding. HLS2 is considered a ciliopathy (summary by Putoux et al., 2011). Acrocallosal syndrome (ACLS; 200990) is an allelic disorder with a less severe phenotype. For a discussion of genetic heterogeneity of hydrolethalus syndrome, see 236680.
Focal segmental glomerulosclerosis-6 is an autosomal recessive childhood-onset kidney disorder manifest clinically by the nephrotic syndrome, which is characterized by proteinuria, hematuria, hypoalbuminemia, and progressive renal failure. It is a disease of the glomerular podocyte (summary by Mele et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Although nails appear normal at birth, dystrophic changes develop within the first decade of life, resulting in onycholysis of fingernails and anonychia of toenails (summary by Rafiq et al., 2004). This disorder is referred to here as nonsyndromic congenital nail disorder-9 (NDNC9). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
Hyperbiliverdinemia can manifest as green jaundice, which is a green discoloration of the skin, urine, serum, and other bodily fluids, due to increased biliverdin resulting from inefficient conversion to bilirubin. Although rarely reported, affected individuals appear to have symptoms only in the context of obstructive cholestasis and/or liver failure. In some cases, green jaundice can resolve after resolution of obstructive cholestasis. Green jaundice has also been associated with malnutrition, medication, and congenital biliary atresia (summary by Huffman et al., 2009).
Nonsyndromic congenital nail disorder-10 is characterized by onychauxis (thick nails), hyponychia, and onycholysis of all nails, with claw-shaped fingernails in some individuals (summary by Frojmark et al., 2011). For a list of other nonsyndromic congenital nail disorders and a discussion of genetic heterogeneity, see NDNC1 (161050).
IMD31C is disorder of immunologic dysregulation with highly variable manifestations resulting from autosomal dominant gain-of-function mutations in STAT1 (600555). Most patients present in infancy or early childhood with chronic mucocutaneous candidiasis (CMC). Other highly variable features include recurrent bacterial, viral, fungal, and mycoplasmal infections, disseminated dimorphic fungal infections, enteropathy with villous atrophy, and autoimmune disorders, such as hypothyroidism or diabetes mellitus. A subset of patients show apparently nonimmunologic features, including osteopenia, delayed puberty, and intracranial aneurysms. Laboratory studies show increased activation of gamma-interferon (IFNG; 147570)-mediated inflammation. (summary by Uzel et al., 2013 and Sampaio et al., 2013).
Delayed sleep phase syndrome is a circadian rhythm sleep disorder characterized by sleep-onset insomnia and difficulty in awakening at the desired time. Patients with DSPD have chronic difficulty in adjusting their sleep-onset and wake-up times to occupational, school, and social activities. Although psychosocial and environmental factors sometimes induce this kind of disorder, most patients with DSPD appear to have an abnormal circadian pacemaker and/or an abnormal entrainment system (summary by Hohjoh et al., 2003).
Brittle cornea syndrome (BCS) is characterized by blue sclerae, corneal rupture after minor trauma, keratoconus or keratoglobus, hyperelasticity of the skin, and hypermobility of the joints (Al-Hussain et al., 2004). It is classified as a form of Ehlers-Danlos syndrome (Malfait et al., 2017). For a discussion of genetic heterogeneity of brittle cornea syndrome, see BCS1 (229200).
This primary immunodeficiency, designated IMD21, DCML, or MONOMAC, is characterized by profoundly decreased or absent monocytes, B lymphocytes, natural killer (NK) lymphocytes, and circulating and tissue dendritic cells (DCs), with little or no effect on T-cell numbers. Clinical features of IMD21 are variable and include susceptibility to disseminated nontuberculous mycobacterial infections, papillomavirus infections, opportunistic fungal infections, and pulmonary alveolar proteinosis. Bone marrow hypocellularity and dysplasia of myeloid, erythroid, and megakaryocytic lineages are present in most patients, as are karyotypic abnormalities, including monosomy 7 and trisomy 8. In the absence of cytogenetic abnormalities or overt dysplasia, hypoplastic bone marrow may initially be diagnosed as aplastic anemia. Bone marrow transplantation is the only cure. Some patients may have an increased risk of miscarriage. Both autosomal dominant transmission and sporadic cases occur. Less common manifestations of GATA2 deficiency include lymphedema and sensorineural hearing loss, a phenotype usually termed 'Emberger syndrome' (614038) (summary by Bigley et al. (2011), Hsu et al. (2011), and Spinner et al. (2014)).
This autosomal recessive disorder is characterized by craniosynostosis, maxillary hypoplasia, and dental anomalies, including malocclusion, delayed and ectopic tooth eruption, and/or supernumerary teeth. Some patients also display minor digit anomalies, such as syndactyly and/or clinodactyly (summary by Nieminen et al., 2011).
The nephrotic syndrome refers to a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema, resulting in end-stage kidney disease if untreated. Inherited defects in podocyte structure and function have been observed in some children with the steroid-resistant subtype of nephrotic syndrome (summary by Ozaltin et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
An anomaly of podocyte morphology characterized by the loss of the interdigitating foot process pattern (generally called foot process effacement; FPE). The term FPE designates the loss of the usual interdigitating pattern of foot processes of neighboring podocytes, leading to relatively broad expanses of podocyte processes covering the glomerular basement membrane (GBM). It is widely viewed as a pathological derangement that is associated with leakage of macromolecules such as albumin through the glomerular filtration barrier.
Nephrotic syndrome type 5 is an autosomal recessive disorder characterized by very early onset of progressive renal failure manifest as proteinuria with consecutive edema starting in utero or within the first 3 months of life. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus (summary by Hasselbacher et al., 2006). Mutation in the LAMB2 gene can also cause Pierson syndrome (609049), which is characterized by nephrotic syndrome, distinct ocular anomalies, namely microcoria, and neurodevelopmental delay. For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Platelet-type bleeding disorder-11 is an autosomal recessive mild to moderate bleeding disorder caused by defective platelet activation and aggregation in response to collagen (summary by Dumont et al., 2009).
Increased length of the hairs of the eyebrows.
Hyperphosphatasia with mental retardation syndrome-3 is an autosomal recessive disorder usually characterized by severe mental retardation, hypotonia with very poor motor development, poor speech, and increased serum alkaline phosphatase (summary by Hansen et al., 2013). However, the severity of the disorder can also vary to include milder intellectual disability (Krawitz et al., 2013). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (239300). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Meckel syndrome is a severe autosomal recessive ciliopathy classically defined by the triad of encephalocele, polydactyly, and renal and biliary ductal dysplasia (summary by Hopp et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Acute encephalopathy is a severe neurologic complication of an infection that usually occurs in children. It is characterized by a high-grade fever accompanied within 12 to 48 hours by febrile convulsions, often leading to coma, multiple-organ failure, brain edema, and high morbidity and mortality. The infections are usually viral, particularly influenza, although other viruses and even mycoplasma have been found to cause the disorder (summary by Chen et al., 2005; Shinohara et al., 2011). For a discussion of genetic heterogeneity of susceptibility to acute infection-induced encephalopathy, see 610551.
Retinal arterial macroaneurysm is an autosomal recessive condition characterized by the bilateral appearance of 'beading' along the major retinal arterial trunks, with the subsequent formation of macroaneurysms. Affected individuals also have supravalvular pulmonic stenosis, often requiring surgical correction (summary by Abu-Safieh et al., 2011).
The chromosome 8q21.11 deletion syndrome is characterized by intellectual disability and common facial dysmorphic features (summary by Palomares et al., 2011).
MEDS is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, simplified gyral pattern, severe epilepsy, and infantile diabetes (summary by Poulton et al., 2011).
Parkinson disease-18 is an autosomal dominant, adult-onset form of the disorder. It is phenotypically similar to idiopathic Parkinson disease (summary by Chartier-Harlin et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of Parkinson disease (PD), see 168600.
NDHMSD is a severe neurodevelopmental disorder characterized by profound developmental delay, severe intellectual disability with absent speech, muscular hypotonia, and a hyperkinetic movement disorder. Additional features may include cortical blindness, generalized cerebral atrophy, and seizures (summary by Lemke et al., 2016).
An autosomal dominant condition caused by mutation(s) in the KIF1A gene, encoding kinesin-like protein KIF1A. It is characterized by microcephaly, intellectual disability, and delayed psychomotor development. The condition is progressive, occurs in early infancy, and is of variable severity.
The microcephaly-capillary malformation (MIC-CAP) syndrome is characterized by microcephaly, generalized cutaneous capillary malformations (ranging from a few to hundreds of oval/circular macules or patches varying in size from 1-2 mm to several cm), hypoplastic distal phalanges of the hands and/or feet, intractable epilepsy, and profound developmental delay. Seizures, which can include focal, tonic, complex partial, and infantile spasms, seem to stabilize after the first two years of life. Myoclonus of the limbs and eyelids is common; other abnormal movements (dyskinetic, choreiform) may be seen. Minimal developmental progress is made after birth. To date the diagnosis has been confirmed in 12 affected individuals (including 2 sibs).
An abnormal hair whorl (that is, a patch of hair growing in the opposite direction of the rest of the hair).
Combined malonic and methylmalonic aciduria (CMAMMA) is a condition characterized by high levels of certain chemicals, known as malonic acid and methylmalonic acid, in the body. A distinguishing feature of this condition is higher levels of methylmalonic acid than malonic acid in the urine, although both are elevated.The signs and symptoms of CMAMMA can begin in childhood. In some children, the buildup of acids causes the blood to become too acidic (ketoacidosis), which can damage the body's tissues and organs. Other signs and symptoms may include involuntary muscle tensing (dystonia), weak muscle tone (hypotonia), developmental delay, an inability to grow and gain weight at the expected rate (failure to thrive), low blood sugar (hypoglycemia), and coma. Some affected children have an unusually small head size (microcephaly).Other people with CMAMMA do not develop signs and symptoms until adulthood. These individuals usually have neurological problems, such as seizures, loss of memory, a decline in thinking ability, or psychiatric diseases.
Juvenile myoclonic epilepsy is a condition characterized by recurrent seizures (epilepsy). This condition begins in childhood or adolescence, usually between ages 12 and 18, and lasts into adulthood. The most common type of seizure in people with this condition is myoclonic seizures, which cause rapid, uncontrolled muscle jerks. People with this condition may also have generalized tonic-clonic seizures (also known as grand mal seizures), which cause muscle rigidity, convulsions, and loss of consciousness. Sometimes, affected individuals have absence seizures, which cause loss of consciousness for a short period that appears as a staring spell. Typically, people with juvenile myoclonic epilepsy develop the characteristic myoclonic seizures in adolescence, then develop generalized tonic-clonic seizures a few years later. Although seizures can happen at any time, they occur most commonly in the morning, shortly after awakening. Seizures can be triggered by a lack of sleep, extreme tiredness, stress, or alcohol consumption.
A type of vitreoretinal degeneration with manifestations that are concentrated at the periphery of the retina.
A hydatidiform mole is an abnormal pregnancy characterized by hydropic placental villi, trophoblastic hyperplasia, and poor fetal development. Familial recurrent hydatidiform mole is an autosomal recessive condition in which women experience recurrent pregnancy losses, predominantly complete hydatidiform mole (CHM). However, unlike sporadic CHMs, which are androgenetic with 2 paternal chromosome complements, CHMs associated with familial recurrence are genetically biparental in origin with both a maternal and a paternal contribution to the genome. Other pregnancy losses in this condition include partial hydatidiform mole, stillbirths, ectopic pregnancies, early neonatal deaths, and miscarriages, some of which may be undiagnosed molar pregnancies. Normal pregnancies are extremely rare in families with this condition (summary by Fallahian et al., 2013). For a discussion of genetic heterogeneity of recurrent hydatidiform mole, see HYDM1 (231090).
Autosomal dominant Wolfram-like syndrome is characterized by the clinical triad of congenital progressive hearing impairment, diabetes mellitus, and optic atrophy. The hearing impairment, which is usually diagnosed in the first decade of life, is relatively constant and alters mainly low- and middle-frequency ranges (summary by Valero et al., 2008). Wolfram syndrome (WFS1; 222300) is an autosomal recessive allelic disorder characterized by optic atrophy, diabetes mellitus, hearing loss, and diabetes insipidus, and is caused by homozygous or compound heterozygous mutation in the WFS1 gene. An autosomal dominant syndrome involving optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy (125250), is caused by heterozygous mutation in the OPA1 gene (605290).
Mitochondrial membrane protein-associated neurodegeneration (MPAN) is characterized initially by gait changes followed by progressive spastic paresis, progressive dystonia (which may be limited to the hands and feet or more generalized), neuropsychiatric abnormalities (e.g., emotional lability, depression, anxiety, impulsivity, compulsions, hallucinations, perseveration, inattention, and hyperactivity), and cognitive decline. Additional early findings can include dysphagia, dysarthria, optic atrophy, axonal neuropathy, parkinsonism, and bowel/bladder incontinence. Survival is usually well into adulthood. End-stage disease is characterized by severe dementia, spasticity, dystonia, and parkinsonism.
Multiple mitochondrial dysfunctions syndrome-2 (MMDS2) with hyperglycinemia is a severe autosomal recessive disorder characterized by developmental regression in infancy. Affected children have an encephalopathic disease course with seizures, spasticity, loss of head control, and abnormal movement. Additional more variable features include optic atrophy, cardiomyopathy, and leukodystrophy. Laboratory studies show increased serum glycine and lactate. Most patients die in childhood. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; 605899), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including MMDS2, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014). For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711).
Hypermethioninemia due to adenosine kinase deficiency is an autosomal recessive inborn error of metabolism characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy); homocysteine is typically normal (summary by Bjursell et al., 2011).
EDICT syndrome is an autosomal dominant syndromal anterior segment dysgenesis characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and thinning of the corneal stroma (Iliff et al., 2012). Syndromes with overlapping features have been reported, including cornea guttata with anterior polar cataracts (121390) and congenital corneal opacities, cornea guttata, and corectopia (608484).
Sclerosteosis is a severe sclerosing bone dysplasia characterized by progressive skeletal overgrowth. Syndactyly is a variable manifestation. The disorder is rare and the majority of affected individuals have been reported in the Afrikaner population of South Africa (summary by Brunkow et al., 2001). For a discussion of genetic heterogeneity of sclerosteosis, see SOST1 (269500).
SCN8A-related epilepsy with encephalopathy is characterized by developmental delay, seizure onset in the first 18 months of life (mean 4 months), and intractable epilepsy characterized by multiple seizure types (generalized tonic-clonic seizures, infantile spasms, and absence and focal seizures). Epilepsy syndromes can include Lennox-Gastaut syndrome, West syndrome, and epileptic encephalopathies (e.g., Dravet syndrome). Hypotonia and movement disorders including dystonia, ataxia, and choreoathetosis are common. Psychomotor development varies from normal prior to seizure onset (with subsequent slowing or regression after seizure onset) to abnormal from birth. Intellectual disability, present in all, ranges from mild to severe (in ~50% of affected individuals). Autistic features are noted in some. Sudden unexpected death in epilepsy (SUDEP) of unknown cause has been reported in approximately 10% of published cases. To date SCN8A-related epilepsy with encephalopathy has been reported in the literature in about 50 individuals.
AMACR deficiency is a rare autosomal recessive peroxisomal disorder characterized by adult onset of variable neurodegenerative symptoms affecting the central and peripheral nervous systems. Features may include seizures, visual failure, sensorimotor neuropathy, spasticity, migraine, and white matter hyperintensities on brain imaging. Serum pristanic acid and C27 bile acid intermediates are increased (summary by Smith et al., 2010).
Autosomal recessive spinocerebellar ataxia-12 is a neurologic disorder characterized by onset of generalized seizures in infancy, delayed psychomotor development with mental retardation, and cerebellar ataxia. Some patients may also show spasticity (summary by Mallaret et al., 2014).
Feingold syndrome is an autosomal dominant disorder characterized by variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disability/mental retardation. Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and fifth fingers, syndactyly (characteristically between second and third and fourth and fifth toes), and shortened or absent middle phalanges. Cardiac and renal malformations, vertebral anomalies, and deafness have also been described in a minority of patients (summary by Teszas et al., 2006). For a discussion of genetic heterogeneity of Feingold syndrome, see FGLDS1 (164280).
BAP1 tumor predisposition syndrome (BAP1-TPDS) is associated with an increased risk for the specific skin lesion – atypical Spitz tumors – and the following cancers, in descending order of frequency: uveal (eye) melanoma (UM), malignant mesothelioma (MMe), cutaneous melanoma (CM), clear cell renal cell carcinoma (ccRCC), and basal cell carcinoma (BCC). Affected individuals can have more than one type of primary cancer. In general the median age of onset of these tumors is younger than in the general population. UM tends to be a more aggressive class 2 tumor with higher risk for metastasis and reduced survival compared to UM that occurs in the general population. However, because of the limited number of families reported to date, the penetrance, natural history, and frequencies of the BAP1-associated tumors are yet to be determined. Other suspected but unconfirmed tumors in BAP1-TPDS include (in alphabetic order): breast cancer, cholangiocarcinoma, non-small cell lung adenocarcinoma (NSCLC), meningioma, and neuroendocrine carcinoma.
Congenital pancreatic lipase deficiency is a rare, monoenzymatic form of exocrine pancreatic failure. All reported patients have presented with similar symptoms and clinical findings, including oily/greasy stools from infancy or early childhood and the absence of discernible pancreatic disease. Failure to thrive has not been observed. Analyses of duodenal contents consistently show a marked decrease of pancreatic lipolytic activity (summary by Figarella et al., 1980).
Pulmonary surfactant metabolism dysfunction-5 (SMDP5) is an autosomal recessive lung disorder manifest clinically and pathologically as pulmonary alveolar proteinosis (PAP). PAP is a rare lung disease characterized by the ineffective clearance of surfactant by alveolar macrophages. This results in the accumulation of surfactant-derived lipoproteinaceous material in the alveoli and terminal bronchioles, causing respiratory failure (summary by Greenhill and Kotton, 2009). For a general phenotypic description and a discussion of genetic heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1 (265120).
Dengue virus is a flavivirus belonging to the family Flaviviridae. Its principal vector is Aedes aegypti, a highly urbanized, daytime-biting mosquito that breeds in stored water. There are 4 antigenetically variant serotypes of dengue virus, DEN-1 to DEN-4, and type-specific immunity against one serotype cannot block infection with another serotype. Disease manifestations following dengue infection range from subclinical infection to severe and fatal disease, with age, gender, genotype, immunologic status, and flavivirus infection history of the host all influencing disease severity. Primary infection is mainly associated with dengue fever (DF). Symptoms of DF typically appear 4 to 7 days after the mosquito bite and include high fever, headache, retroocular pain, conjunctival changes, and facial flushing. Although primary dengue infections are mostly recovered, a secondary infection with a different serotype of the virus leads to the complex condition of dengue hemorrhagic fever (DHF) with plasma leakage and thrombocytopenia or a more fatal condition, dengue shock syndrome (DSS). High fever, hemorrhagic phenomenon, hepatomegaly, and circulatory failure are mainly associated with DHF. Hemorrhages in DHF are seen in skin, subcutaneous tissues, heart, liver, and gastrointestinal tract. An estimated 50 to 100 million illnesses due to dengue infection occur annually, including 250,000 to 500,000 cases of DHF and 24,000 deaths. About 2.5 billion people are estimated to be at risk, particularly those living in tropical and subtropical areas of Asia and Latin America (reviews by Faheem et al. (2011), Whitehorn and Simmons (2011), and Guzman et al. (2010)).
Mannose-binding lectin (MBL) deficiency, defined as MBL protein level of less than 100 ng/ml, is present in about 5% of people of European descent and in about 10% of sub-Saharan Africans. Most MBL-deficient adults appear healthy, but low levels of MBL are associated with increased risk of infection in toddlers, in cancer patients undergoing chemotherapy, and in organ-transplant patients receiving immunosuppressive drugs, particularly recipients of liver transplants (review by Degn et al., 2011). MBL is a soluble molecule that can activate the lectin pathway of the complement system; deficiency may thus lead to defects in the complement system (summary by Garcia-Laorden et al., 2008). Genetic Heterogeneity of Lectin Complement Activation Pathway Defects See also LCAPD2 (613791), caused by variation in the MASP2 gene (605102) on chromosome 1p36, and LCAPD3 (613860), caused by variation in the FCN3 gene (604973) on chromosome 1p36.
A reduced level of the complement component C4b in circulation.
Encephalopathy due to defective mitochondrial and peroxisomal fission-1 is characterized by delayed psychomotor development and hypotonia that may lead to death in childhood. Many patients develop refractory seizures, consistent with an epileptic encephalopathy, and thereafter show neurologic decline. The age at onset, features, and severity are variable, and some patients may not have clinical evidence of mitochondrial or peroxisomal dysfunction (summary by Sheffer et al., 2016; Fahrner et al., 2016). Genetic Heterogeneity of Encephalopathy Due to Defective Mitochondrial And Peroxisomal Fission See also EMPF2 (617086), caused by mutation in the MFF gene (614785) on chromosome 2q36.
Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks of gestation. Recurrent miscarriage, defined as 3 or more consecutive pregnancy losses, affects about 1% of couples; when defined as 2 or more losses, the scale of the problem increases to 5% of all couples trying to conceive (summary by Rai and Regan, 2006). Pregnancy losses have traditionally been designated 'spontaneous abortions' if they occur before 20 weeks gestation and 'stillbirths' if they occur after 20 weeks. Subtypes of spontaneous abortions can be further distinguished on the basis of embryonic development and include anembryonic loss in the first 5 weeks after conception (so-called 'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal loss from 10 weeks' gestation through the remainder of the pregnancy. These distinctions are important because the causes of pregnancy loss vary over gestational ages, with anembryonic losses being more likely to be associated with chromosomal abnormalities, for example. Possible etiologies for RPRGL include uterine anatomic abnormalities, cytogenetic abnormalities in the parents or fetus, single gene disorders, thrombophilic conditions, and immunologic or endocrine factors as well as environmental or infectious agents (summary by Warren and Silver, 2008). Genetic Heterogeneity of Recurrent Pregnancy Loss Susceptibility to RPRGL2 (614390) is conferred by mutation in the coagulation factor II gene (176930) on chromosome 11p11; RPRGL3 (614391) by mutation in the ANXA5 gene (131230) on chromosome 4q27; and RPRGL4 (see 270960) by mutation in the SYCP3 gene (604759) on chromosome 12q23. Genetic variation in the conceptus itself that results in decreased viability of the embryo or fetus is discussed in the respective gene and/or phenotype entry (see, e.g., MTHFR, 607093.0004; NLRP7, 609661; hydatidiform mole, 231090).
Miscarriage, the commonest complication of pregnancy, is the spontaneous loss of a pregnancy before the fetus has reached viability. The term therefore includes all pregnancy losses from the time of conception until 24 weeks of gestation. Recurrent miscarriage, defined as 3 or more consecutive pregnancy losses, affects about 1% of couples; when defined as 2 or more losses, the scale of the problem increases to 5% of all couples trying to conceive (summary by Rai and Regan, 2006). Pregnancy losses have traditionally been designated 'spontaneous abortions' if they occur before 20 weeks' gestation and 'stillbirths' if they occur after 20 weeks. Subtypes of spontaneous abortions can be further distinguished on the basis of embryonic development and include anembryonic loss in the first 5 weeks after conception (so-called 'blighted ovum'), embryonic loss from 6 to 9 weeks' gestation, and fetal loss from 10 weeks' gestation through the remainder of the pregnancy. These distinctions are important because the causes of pregnancy loss vary over gestational ages, with anembryonic losses being more likely to be associated with chromosomal abnormalities, for example. Possible etiologies for recurrent pregnancy loss include uterine anatomic abnormalities, cytogenetic abnormalities in the parents or fetus, single gene disorders, thrombophilic conditions, and immunologic or endocrine factors as well as environmental or infectious agents (summary by Warren and Silver, 2008).
Transplantation of hematopoietic stem cells is a successful therapy for some tumors derived from bone marrow precursors, such as certain leukemias and lymphomas, and it can be used to cure some primary immunodeficiencies and inherited hematopoietic stem-cell diseases. One of the major complications of allogeneic bone marrow transplantation is graft-versus-host disease (GVHD), in which mature donor T cells that contaminate the allogeneic bone marrow recognize the tissues of the recipient as foreign, causing a severe inflammatory disease characterized by rashes, diarrhea, and liver disease. GVHD is particularly virulent when there is a mismatch of a major major histocompatibility complex (MHC) class I or class II antigen. Most transplants are therefore undertaken only when the donor and recipient are HLA-matched sibs or, less frequently, when there is an HLA-matched unrelated donor. However, GVHD also occurs in the context of disparities between minor histocompatibility antigens, and immunosuppression must be used in every stem-cell transplant (summary by Janeway et al., 2005). At the core of the immunogenetic basis for GVHD is the diversity of HLA, killer immunoglobulin-like receptors (KIRs; see 604936), and cytokine genes. HLA class I molecules function as ligands for natural killer cell inhibitory KIRs, indicating that GVHD results from a complex interplay between innate and adaptive immune responses. Cytokines may modulate the intensity of tissue injury and inflammation in GVHD, and therefore cytokine polymorphisms in either patient or donor or both may explain individual risks of GVHD (review by Petersdorf and Malkki, 2006).
EMARDD is a congenital myopathy characterized by proximal and generalized muscle weakness, respiratory difficulties, joint contractures, and scoliosis. More variable features include cleft palate and feeding difficulties. There is variable severity: some patients become ventilator-dependent, never achieve walking, and die in childhood, whereas others have a longer and more favorable course (summary by Logan et al., 2011 and Boyden et al., 2012).
The Zaki-Gleeson syndrome is an autosomal recessive neurodevelopmental disorder characterized by profound mental retardation, severe microcephaly, poor growth, cerebellar hypoplasia, and second-degree cardiac conduction defects (summary by Zaki et al., 2011).
A lack of coordination of arm movement manifested by undershoot or overshoot of the intended position of the arm. [HPO:mtaboada, PMID:20301629]
Chilblain lupus is a rare cutaneous form of systemic lupus erythematosus (SLE; 152700) characterized by tender, bluish-red swellings and nodules on the hands, feet, ears, and nose, with histologic changes of lupus. The phenotype is induced by cold, such that patients frequently report a worsening of lesions in the winter months (summary by Ravenscroft et al., 2011). For a general description and a discussion of genetic heterogeneity of chilblain lupus, see CHBL1 (610448).
Familial febrile seizures-11 is an autosomal recessive seizure disorder characterized by early childhood onset of simple or complex seizures associated with fever. These seizures usually remit later in childhood with no neurologic sequelae (summary by Salzmann et al., 2012). For a general description and a discussion of genetic heterogeneity of familial febrile seizures, see FEB1 (121210).
Systemic lupus erythematosus (SLE) diagnosed in individuals under the age of eighteen. Children frequently have multi-organ involvement and acute disease onset. Symptoms include fever, arthritis, skin lesions, anemia, and fatigue.
An abnormality of the fossa cranii posterior (the posterior fossa), which is made up primarily of the occipital bone and which surrounds to the foramen magnum.
Absence or underdevelopment of the vermis of cerebellum.
Ventricular septal defect (VSD) is the most common form of congenital cardiovascular anomaly, occurring in nearly 50% of all infants with a congenital heart defect and accounting for 14 to 16% of cardiac defects that require invasive treatment within the first year of life. Congenital VSDs may occur alone or in combination with other cardiac malformations. Large VSDs that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death (summary by Wang et al., 2011, 2011). Other congenital cardiac defects caused by mutation in the GATA4 gene include atrial septal defect (ASD2; 607941), tetralogy of Fallot (see TOF, 187500), and endocardial cushion defects (AVSD4; 614430). Genetic Heterogeneity of Ventricular Septal Defect VSD2 (614431) is caused by mutation in the CITED2 gene (602937) on chromosome 6q24; VSD3 (614432) is caused by mutation in the NKX2-5 gene (600584) on chromosome 5q34. Somatic mutations in the HAND1 gene (602406) have been identified in tissue samples from patients with VSD.
The term 'atrioventricular septal defect' (AVSD) covers a spectrum of congenital heart malformations characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. In ostium primum atrial septal defect (ASD) there are separate atrioventricular valvar orifices despite a common junction, whereas in complete AVSD the valve itself is also shared (summary by Craig, 2006). AVSD, also designated endocardial cushion defect or atrioventricular canal defect (AVCD), is known to occur in either a nonsyndromic (isolated) form or, more commonly, as part of a malformation syndrome. The 2 syndromes most frequently associated with AVSD are Down syndrome (190685), in which AVSD is the most frequent congenital heart defect, and Ivemark syndrome (208530) (summary by Carmi et al., 1992). For a discussion of genetic heterogeneity of atrioventricular septal defects, see AVSD1 (606215).
Ventricular septal defect (VSD) is the most common form of congenital cardiovascular anomaly, occurring in nearly 50% of all infants with a congenital heart defect and accounting for 14% to 16% of cardiac defects that require invasive treatment within the first year of life. Congenital VSDs may occur alone or in combination with other cardiac malformations. Large VSDs that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death (summary by Wang et al., 2011, 2011). For a discussion of genetic heterogeneity of ventricular septal defect, see VSD1 (614429).
Ventricular septal defect (VSD) is the most common form of congenital cardiovascular anomaly, occurring in nearly 50% of all infants with a congenital heart defect and accounting for 14 to 16% of cardiac defects that require invasive treatment within the first year of life. Congenital VSDs may occur alone or in combination with other cardiac malformations. Large VSDs that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death (summary by Wang et al., 2011, 2011). Other congenital cardiac defects caused by mutation in the NKX2-5 gene include atrial septal defect with or without atrioventricular conduction defects (ASD7; 108900), tetralogy of Fallot (see TOF, 187500), conotruncal malformations (see 217095), and hypoplastic left heart syndrome (HLHS2; 614435). For a discussion of genetic heterogeneity of ventricular septal defect, see VSD1 (614429).
FBLN5-related cutis laxa is characterized by cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonary artery stenosis, and other evidence of a generalized connective disorder such as inguinal hernias and hollow viscus diverticula (e.g., intestine, bladder). Occasionally, supravalvular aortic stenosis is observed. Intrafamilial variability in age of onset is observed. Cardiorespiratory failure from complications of pulmonary emphysema (respiratory or cardiac insufficiency) is the most common cause of death.
Hypoplastic left heart syndrome results from defective development of the aorta proximal to the entrance of the ductus arteriosus and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged (Brekke, 1953). For a discussion of genetic heterogeneity of hypoplastic left heart syndrome, see HLHS1 (241550).
EFEMP2-related cutis laxa, or autosomal recessive cutis laxa type 1B (ARCL1B), is characterized by cutis laxa and systemic involvement, most commonly arterial tortuosity, aneurysms, and stenosis; retrognathia; joint laxity; and arachnodactyly. Severity ranges from perinatal lethality as a result of cardiopulmonary failure to manifestations limited to the vascular and craniofacial systems.
De Barsy syndrome, also known as autosomal recessive cutis laxa type III (ARCL3), is a rare autosomal recessive disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation (IUGR), and cutis laxa (summary by Lin et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of de Barsy syndrome, see 219150. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see 219200.
Primary hypertrophic osteoarthropathy (PHO), which is also known as pachydermoperiostosis, is a rare genetic disease that affects the skin and bones. PHO is characterized by digital clubbing, periostosis, acroosteolysis, painful joint enlargement, and skin manifestations that include thickened facial skin, a thickened scalp, and coarse facial features (summary by Zhang et al., 2012). For a discussion of genetic heterogeneity of PHO, see PHOAR1 (259100).
Autosomal dominant intermediate Charcot-Marie-Tooth disease E with focal segmental glomerulonephritis is characterized by the neurologic features of CMT, including distal muscle weakness and atrophy and distal sensory loss, and the features of FSGS, including proteinuria, progression to end-stage renal disease, and a characteristic histologic pattern on renal biopsy (summary by Boyer et al., 2011). Isolated focal segmental glomerulosclerosis-5 (FSGS5; 613237) is also caused by heterozygous mutation in the INF2 gene. For a discussion of genetic heterogeneity of CMTDI, see 606482.
ISQMR is a severe autosomal recessive disorder characterized by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures (summary by Aldahmesh et al., 2011).
Episodic encephalopathy due to thiamine pyrophosphokinase deficiency is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits (summary by Mayr et al., 2011). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270).
Hyperglycinemia, lactic acidosis, and seizures is a severe autosomal recessive disorder characterized by onset of hypotonia and seizures associated with increased serum glycine and lactate in the first days of life. Affected individuals develop an encephalopathy or severely delayed psychomotor development, which may result in death in childhood. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; 605899), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including HGCLAS, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014).
Familial cold autoinflammatory syndrome-2 is an autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritus in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B cells, defective B cells, increased susceptibility to infection, and increased risk of autoimmune disorders (summary by Ombrello et al., 2012). For a discussion of genetic heterogeneity of FCAS, see FCAS1 (120100).
Anatomic features of unbalanced atrioventricular septal defect (AVSD) include varying amounts of ventricular hypoplasia, as well as malalignment of the atrioventricular junction. In complete AVSD, the common AV valve can be situated either equally over the right and left ventricles (balanced) or unequally over the ventricles (unbalanced).
Transient infantile hypertriglyceridemia is an autosomal recessive disorder characterized by onset of moderate to severe transient hypertriglyceridemia in infancy that normalizes with age. The hypertriglyceridemia is associated with hepatomegaly, moderately elevated transaminases, persistent fatty liver, and the development of hepatic fibrosis. The long-term outcome of affected individuals is unclear (summary by Basel-Vanagaite et al., 2012).
Congenital cataracts, hearing loss, and neurodegeneration (CCHLND) is an autosomal recessive disorder characterized by congenital cataracts, severe psychomotor retardation, and hearing loss associated with decreased serum ceruloplasmin and copper. Brain MRI shows cerebral and cerebellar atrophy and hypomyelination (summary by Huppke et al., 2012).
Brain small vessel disease-2 is an autosomal dominant disorder characterized by variable neurologic impairment resulting from disturbed vascular supply that leads to cerebral degeneration. The disorder is often associated with 'porencephaly' on brain imaging. Affected individuals typically have hemiplegia, seizures, and intellectual disability, although the severity is variable (summary by Yoneda et al., 2012). For a discussion of genetic heterogeneity of brain small vessel disease, see BSVD1 (175780).
Trigonocephaly occurs predominantly as a nonsyndromic craniosynostosis and has an estimated prevalence of between 1:15,000 and 1:68,000 live births (summary by Vissers et al., 2011). For a discussion of genetic heterogeneity of isolated trigonocephaly, see TRIGNO1 (190440). A syndromic form of trigonocephaly is associated with monosomy for an 8-Mb interval of chromosome 9p22.3 (see 158170).
The role of thrombomodulin in thrombosis is controversial. Although there have been several reports of THBD mutations in patients with venous thrombosis, clear functional evidence for the pathogenicity of these mutations is lacking. In a review, Anastasiou et al. (2012) noted that thrombomodulin has a major role in capillary beds and that THBD variation may not be associated with large vessel thrombosis. It is likely that genetic or environmental risk factors in addition to THBD variation are involved in the pathogenesis of venous thrombosis. However, variation in the THBD gene may be associated with increased risk for arterial thrombosis and myocardial infarction. This association may be attributed to the fact that thrombomodulin can modulate inflammatory processes, complement activity, and fibrinolysis.
Spastic ataxia-5 (SPAX5) is an autosomal recessive neurodegenerative disorder characterized by early-onset spasticity resulting in significantly impaired ambulation, cerebellar ataxia, oculomotor apraxia, dystonia, and myoclonic epilepsy (summary by Pierson et al., 2011). For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600).
Lethal neonatal rigidity and multifocal seizure syndrome is a severe autosomal recessive epileptic encephalopathy characterized by onset of rigidity and intractable seizures at or soon after birth. Affected infants achieve no developmental milestones and die within the first months or years of life (summary by Saitsu et al., 2014).
Seizures that start from several different areas of the brain (i.e., with multiple ictal onset locations).
MRT34 is an autosomal recessive neurologic disorder characterized by mild to moderate intellectual disability and megalencephaly or enlarged head circumference. Brain imaging shows a mild variant of lissencephaly with anterior-predominant pachygyria with shallow and unusually wide sulci and mildly thickened cortex. Some patients may have seizures (summary by Di Donato et al., 2016).
Cone-rod dystrophy (CORD) and retinitis pigmentosa (RP) are clinically and genetically overlapping heterogeneous retinal dystrophies. RP is characterized initially by rod photoreceptor dysfunction, giving rise to night blindness, which is followed by progressive rod and cone photoreceptor dystrophy, resulting in midperipheral vision loss, tunnel vision, and sometimes blindness. In contrast to RP, CORD is characterized by a primary loss of cone photoreceptors and subsequent or simultaneous loss of rod photoreceptors. The disease in most cases becomes apparent during primary-school years, and symptoms include photoaversion, decrease in visual acuity with or without nystagmus, color vision defects, and decreased sensitivity of the central visual field. Because rods are also involved, night blindness and peripheral vision loss can occur. The diagnosis of CORD is mainly based on electroretinogram (ERG) recordings, in which cone responses are more severely reduced than, or equally as reduced as rod responses (summary by Estrada-Cuzcano et al., 2012).
Bigonial distance (lower facial width) more than 2 SD above the mean (objective); or an apparently increased width of the lower jaw (mandible) when viewed from the front (subjective).
Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995). For a discussion of genetic heterogeneity of type III Usher syndrome, see USH3A (276902).
A form of congenital disorders of N-linked glycosylation with characteristics of failure to thrive, developmental delay, hypotonia, strabismus and hepatic dysfunction. The disease is caused by mutations in the gene DDOST (1p36.1).
Autosomal recessive thrombophilia due to protein S deficiency is a very rare and severe hematologic disorder resulting in thrombosis and secondary hemorrhage usually beginning in early infancy. Some affected individuals develop neonatal purpura fulminans, multifocal thrombosis, or intracranial hemorrhage (Pung-amritt et al., 1999; Fischer et al., 2010), whereas others have recurrent thromboses later in childhood (Comp et al., 1984). See also autosomal dominant thrombophilia due to protein S deficiency (THPH5; 612336), a less severe disorder caused by heterozygous mutation in the PROS1 gene.
Thrombocythemia-3 is an autosomal dominant hematologic disorder characterized by increased platelet production resulting in increased numbers of circulating platelets. Thrombocythemia can be associated with thrombotic episodes, such as cerebrovascular events or myocardial infarction (summary by Mead et al., 2012). For a discussion of genetic heterogeneity of thrombocythemia, see THCYT1 (187950).
Fibrochondrogenesis is a severe skeletal dysplasia characterized by a flat midface, short long bones, short ribs with broad metaphyses, and vertebral bodies that show distinctive hypoplastic posterior ends and rounded anterior ends, giving the vertebral bodies a pinched appearance on lateral radiographic views. The chest is small, causing perinatal respiratory problems which usually, but not always, result in lethality. Affected individuals who survive the neonatal period have high myopia, mild to moderate hearing loss, and severe skeletal dysplasia (summary by Tompson et al., 2012). For a discussion of genetic heterogeneity of fibrochondrogenesis, see FBCG1 (228520).
In individuals with clinical manifestations the 17q12 recurrent duplication is characterized by intellectual abilities ranging from normal to severe disability and other variable clinical manifestations. Speech delay is common, and most affected individuals have some degree of gross motor delay. Seizures are present in 75%. Up to one third have eye or vision problems; cardiac and renal anomalies occur in rare cases. Other neurodevelopmental and psychiatric conditions reported in a subset of affected individuals are autism spectrum disorder, schizophrenia, and behavioral abnormalities (aggression and self-injury). The 17q12 recurrent duplication likely has reduced penetrance and variable expressivity since it is inherited in most instances from a parent who is often minimally affected or phenotypically normal.
The interstitial 16q22 deletion syndrome is a multiple congenital anomaly disorder associated with failure to thrive in infancy, poor growth, delayed psychomotor development, hypotonia, and dysmorphic features, including large anterior fontanel, high forehead, diastasis of the cranial sutures, broad nasal bridge, hypertelorism, low-set abnormal ears, and short neck. The phenotypic features and deletion sizes are variable, but deletion of 16q22 appears to be critical for manifestations of the syndrome (summary by Fujiwara et al., 1992).
Highly active antiretroviral therapy (HAART) has reduced mortality associated with acquired immunodeficiency syndrome (AIDS; see 609423) by at least 70%. Efavirenz is a non-nucleoside reverse transcriptase inhibitor that is frequently prescribed with 2 nucleoside reverse transcriptase inhibitors as initial therapy for human immunodeficiency virus (HIV) infection. However, during the first weeks of therapy, up to half of patients who receive efavirenz experience CNS side effects, including dizziness, insomnia, impaired concentration, somnolence, and abnormal dreams. Severe depression, aggressive behavior, and paranoid or manic reactions may also occur, and such side effects may reflect varying efavirenz plasma concentrations. Plasma clearance of efavirenz appears slower in African Americans than in European Americans, and studies have suggested earlier virologic failure on efavirenz for both African Americans and Hispanics compared with European Americans. Efavirenz is metabolized primarily by hepatic CYP2B6, with some involvement of CYP3A (CYP3A4; 124010) (summary by Haas et al., 2004).
Ehlers-Danlos syndrome kyphoscoliotic type 2 is characterized by severe muscle hypotonia at birth, progressive scoliosis, joint hypermobility, hyperelastic skin, myopathy, sensorineural hearing impairment, and normal pyridinoline excretion in urine (Baumann et al., 2012). For a discussion of genetic heterogeneity of the kyphoscoliotic type of EDS, see 225400.
Infantile cerebellar-retinal degeneration is a severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration (summary by Spiegel et al., 2012).
Leukoencephalopathy, brain calcifications, and cysts (LCC), also known as Labrune syndrome, is characterized by a constellation of features restricted to the central nervous system, including leukoencephalopathy, brain calcifications, and cysts, resulting in spasticity, dystonia, seizures, and cognitive decline (summary by Labrune et al., 1996). See also cerebroretinal microangiopathy with calcifications and cysts (CRMCC; 612199), an autosomal recessive disorder caused by mutation in the CTC1 gene (613129) that shows phenotypic similarities to Labrune syndrome. CRMCC includes the neurologic findings of intracranial calcifications, leukodystrophy, and brain cysts, but also includes retinal vascular abnormalities and other systemic manifestations, such as osteopenia with poor bone healing, a high risk of gastrointestinal bleeding, hair, skin, and nail changes, and anemia and thrombocytopenia. Although Coats plus syndrome and Labrune syndrome were initially thought to be manifestations of the same disorder, namely CRMCC, molecular evidence has excluded mutations in the CTC1 gene in patients with Labrune syndrome, suggesting that the 2 disorders are not allelic (Anderson et al., 2012; Polvi et al., 2012).
Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or central nervous systems. Other findings commonly include feeding difficulties, slow growth, ophthalmologic abnormalities, and hearing impairment.
MRD13 is an autosomal dominant form of mental retardation associated with variable neuronal migration defects resulting in cortical malformations. More variable features include early-onset seizures and mild dysmorphic features. Some patients may also show signs of peripheral neuropathy, such as abnormal gait, hyporeflexia, and foot deformities (summary by Willemsen et al., 2012 and Poirier et al., 2013).
Patients with this syndrome develop cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well (Tanaka et al., 2012).
Complete congenital stationary night blindness (cCSNB) is a clinically and genetically heterogeneous group of retinal disorders characterized by nonprogressive impairment of night vision, absence of the electroretinogram (ERG) b-wave, and variable degrees of involvement of other visual functions. Individuals with cCSNB and animal models of the disorder have an ERG waveform that lacks the b-wave because of failure to transmit the photoreceptor signal through the retinal depolarizing bipolar cells (summary by Peachey et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500).
Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an autosomal recessive adult-onset, slowly progressive neurologic disorder characterized by imbalance due to cerebellar gait and limb ataxia, impaired vestibular function bilaterally, and non-length-dependent sensory neuropathy (summary by Szmulewicz et al., 2011).
Dystonia-21 (DYT21) is an autosomal dominant form of pure torsion dystonia, a movement disorder characterized by sustained muscle contractions causing twisting and repetitive movements and abnormal postures (summary by Norgren et al., 2011).
Podoconiosis, or endemic nonfilarial elephantiasis, is a noninfectious geochemical disease characterized by edema of the foot and lower leg that progresses to severe elephantiasis. It is a chronic and debilitating disorder that is a public health problem in at least 10 countries in tropical Africa, Central America, and northern India. Podoconiosis occurs among subsistence farmers and other occupational groups whose feet are exposed over many years to red clay soil derived from alkalic volcanic rock. However, podoconiosis develops only in a subgroup of exposed people, and studies have shown familial clustering with high heritability (summary by Davey et al. (2007) and Tekola Ayele et al. (2012)).
Trichohepatoenteric syndrome (THES), generally considered to be a neonatal enteropathy, is characterized by intractable diarrhea (seen in almost all affected children), woolly hair (seen in all), intrauterine growth restriction, facial dysmorphism, and short stature. Additional findings include poorly characterized immunodeficiency, recurrent infections, skin abnormalities, and liver disease. Mild intellectual disability (ID) is seen in about 50% of affected individuals. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported.
Autosomal dominant deafness-4B is a form of nonsyndromic progressive sensorineural hearing loss with postlingual onset (summary by Wang et al., 2015)
A carcinoma that has spread to the liver from another primary anatomic site. Representative examples include metastatic carcinomas from the colon, breast, and lung.
A hemangioma with cavernous vascular spaces arising from the liver. It is the most frequent benign tumor of the liver and usually affects young females.
Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematologic stem cell disorders characterized by ineffective hematopoiesis resulting in low blood counts, most commonly anemia, and a risk of progression to acute myeloid leukemia (AML; 601626). Blood smears and bone marrow biopsies show dysplastic changes in myeloid cells, with abnormal proliferation and differentiation of 1 or more lineages (erythroid, myeloid, megakaryocytic). MDS can be subdivided into several categories based on morphologic characteristics, such as low-grade refractory anemia (RA) or high-grade refractory anemia with excess blasts (RAEB). Bone marrow biopsies of some patients show ringed sideroblasts (RARS), which reflects abnormal iron staining in mitochondria surrounding the nucleus of erythrocyte progenitors (summary by Delhommeau et al., 2009 and Papaemmanuil et al., 2011).
An anhydrous sodium salt formulation of phosphonoacetic acid with activity against herpes simplex viruses and other members of the herpes virus family. Fosfonet inhibits viral DNA polymerase and inhibits the synthesis of viral DNA.
A hydatidiform mole is an abnormal pregnancy characterized by hydropic placental villi, trophoblastic hyperplasia, and poor fetal development. Familial recurrent hydatidiform mole is an autosomal recessive condition in which women experience recurrent pregnancy losses, predominantly complete hydatidiform mole (CHM). However, unlike sporadic CHMs, which are androgenetic with 2 paternal chromosome complements, CHMs associated with familial recurrence are genetically biparental in origin with both a maternal and a paternal contribution to the genome. Other pregnancy losses in this condition include partial hydatidiform mole, stillbirths, ectopic pregnancies, early neonatal deaths, and miscarriages, some of which may be undiagnosed molar pregnancies. Normal pregnancies are extremely rare in families with this condition (summary by Fallahian et al., 2013). Genetic Heterogeneity of Recurrent Hydatidiform Mole Another form of recurrent complete hydatidiform mole (HYDM2; 614293) is caused by mutation in the KHDC3L gene (611687) on chromosome 6q13.
CMO type II deficiency is an autosomal recessive disorder caused by a defect in the final biochemical step of aldosterone biosynthesis, the 18-hydroxylation of 18-hydroxycorticosterone (18-OHB) to aldosterone. This enzymatic defect results in decreased aldosterone and salt-wasting associated with an increased serum ratio of 18-OHB to aldosterone. In CMO II deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18-OHB. These patients have a low ratio of corticosterone to 18-OHB (Portrat-Doyen et al., 1998). The CYP11B2 gene product also catalyzes an earlier step in aldosterone biosynthesis: the 18-hydroxylation of corticosterone to 18-OHB. A defect in that enzymatic step results in CMO type I deficiency (204300), an allelic disorder with an overlapping phenotype but distinct biochemical features. In CMO I deficiency, aldosterone is undetectable, whereas its immediate precursor, 18-OHB, is low or normal (Portrat-Doyen et al., 1998).
Early infantile epileptic encephalopathy is a severe form of epilepsy first reported by Ohtahara et al. (1976). It is characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Approximately 75% of EIEE patients progress to 'West syndrome,' which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG (Kato et al., 2007). Deprez et al. (2009) reviewed the genetics of epilepsy syndromes starting in the first year of life and included a diagnostic algorithm. EIEE1 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1) to syndromic (309510) and nonsyndromic (300419) mental retardation. Although males with ARX mutations are often more severely affected, female mutation carriers may also be affected (Kato et al., 2004; Wallerstein et al., 2008). Genetic Heterogeneity of Early Infantile Epileptic Encephalopathy EIEE is a genetically heterogeneous disorder. Also see EIEE2 (300672), caused by mutation in the CDKL5 gene (300203); EIEE3 (609304), caused by mutation in the SLC25A22 gene (609302); EIEE4 (612164), caused by mutation in the STXBP1 gene (602926); EIEE5 (613477), caused by mutation in the SPTAN1 gene (182810); EIEE6 (607208), also known as Dravet syndrome, caused by mutation in the SCN1A gene (182389); EIEE7 (613720), caused by mutation in the KCNQ2 gene (602235); EIEE8 (300607), caused by mutation in the ARHGEF9 gene (300429); EIEE9 (300088), caused by mutation in the PCDH19 gene (300460); EIEE10 (613402), caused by mutation in the PNKP gene (605610); EIEE11 (613721), caused by mutation in the SCN2A gene (182390); EIEE12 (613722), caused by mutation in the PLCB1 gene (607120); EIEE13 (614558), caused by mutation in the SCN8A gene (600702); EIEE14 (614959), caused by mutation in the KCNT1 gene (608167); EIEE15 (615006), caused by mutation in the ST3GAL3 gene (606494); EIEE16 (615338), caused by mutation in the TBC1D24 gene (613577); EIEE17 (615473), caused by mutation in the GNAO1 gene (139311); EIEE18 (615476), caused by mutation in the SZT2 gene (615463); EIEE19 (615744), caused by mutation in the GABRA1 gene (137160); EIEE20 (300868), caused by mutation in the PIGA gene (311770); EIEE21 (615833), caused by mutation in the NECAP1 gene (611623); EIEE22 (300896), caused by mutation in the SLC35A2 gene (314375); EIEE23 (615859), caused by mutation in the DOCK7 gene (615730); EIEE24 (615871), caused by mutation in the HCN1 gene (602780); EIEE25 (615905), caused by mutation in the SLC13A5 gene (608305); EIEE26 (616056), caused by mutation in the KCNB1 gene (600397); EIEE27 (616139), caused by mutation in the GRIN2B gene (138252); EIEE28 (616211), caused by mutation in the WWOX gene (605131); EIEE29 (616339), caused by mutation in the AARS gene (601065); EIEE30 (616341), caused by mutation in the SIK1 gene (605705); EIEE31 (616346), caused by mutation in the DNM1 gene (602377); EIEE32 (616366), caused by mutation in the KCNA2 gene (176262); EIEE33 (616409), caused by mutation in the EEF1A2 gene (602959); EIEE34 (616645), caused by mutation in the SLC12A5 gene (606726); EIEE35 (616647), caused by mutation in the ITPA gene (147520); EIEE36 (300884), caused by mutation in the ALG13 gene (300776); EIEE37 (616981), caused by mutation in the FRRS1L gene (604574); EIEE38 (617020), caused by mutation in the ARV1 gene (611647); EIEE39 (612949), caused by mutation in the SLC25A12 gene (603667); EIEE40 (617065), caused by mutation in the GUF1 gene (617064); EIEE41 (617105), caused by mutation in the SLC1A2 gene (600300); EIEE42 (617106), caused by mutation in the CACNA1A gene (601011); EIEE43 (617113), caused by mutation in the GABRB3 gene (137192); EIEE44 (617132), caused by mutation in the UBA5 gene (610552); EIEE45 (617153), caused by mutation in the GABRB1 gene (137190); EIEE46 (617162), caused by mutation in the GRIN2D gene (602717); EIEE47 (617166), caused by mutation in the FGF12 gene (601513); EIEE48 (617276), caused by mutation in the AP3B2 gene (602166); EIEE49 (617281), caused by mutation in the DENND5A gene (617278); EIEE50 (616457) caused by mutation in the CAD gene (114010); EIEE51 (617339), caused by mutation in the MDH2 gene (154100); EIEE52 (617350), caused by mutation in the SCN1B gene (600235); EIEE53 (617389), caused by mutation in the SYNJ1 gene (604297); EIEE54 (617391), caused by mutation in the HNRNPU gene (602869); EIEE55 (617599), caused by mutation in the PIGP gene (605938); EIEE56 (617665), caused by mutation in the YWHAG gene (605356); EIEE57 (617771), caused by mutation in the KCNT2 gene (610044); EIEE58 (617830), caused by mutation in the NTRK2 gene (600456); EIEE59 (617904), caused by mutation in the GABBR2 gene (607340); EIEE60 (617929), caused by mutation in the CNPY3 gene (610774); EIEE61 (617933), caused by mutation in the ADAM22 gene (603709); EIEE62 (617938), caused by mutation in the SCN3A gene (182391); EIEE63 (617976), caused by mutation in the CPLX1 gene (605032); EIEE64 (618004), caused by mutation in the RHOBTB2 gene (607352); EIEE65 (618008), caused by mutation in the CYFIP2 gene (606323); EIEE66 (618067), caused by mutation in the PACS2 gene (610423); EIEE67 (618141), caused by mutation in the CUX2 gene (610648); EIEE68 (618201), caused by mutation in the TRAK1 gene (608112); EIEE69 (618285), caused by mutation in the CACNA1E gene (601013); EIEE70 (618298) caused by mutation in the PHACTR1 gene (608723); EIEE71 (618328), caused by mutation in the GLS gene (138280); EIEE72 (618374), caused by mutation in the NEUROD2 gene (601725); EIEE73 (618379), caused by mutation in the RNF13 gene (609247); and EIEE74 (618396), caused by mutation in the GABRG2 gene (137164). The phenotype is also observed in other genetic disorders, including GLUT1 deficiency syndrome (606777); glycine encephalopathy (605899); Aicardi-Goutieres syndrome (225750); and in males with MECP2 mutations (300673), among others. For associations pending confirmation, see MOLECULAR GENETICS.
Aluminosilicate salts of calcium, the most common of which are CaAl2Si2O8 and Ca2Al2SiO7; a naturally occurring form in CLAY may be used to treat DIARRHEA.
A recombinant, fully human monoclonal antibody directed against the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. Anti-IGF-1R fully human monoclonal antibody SCH 717454 binds to membrane-bound IGF-1R, preventing binding of the ligand IGF-1 and the subsequent triggering of the PI3K/Akt signaling pathway; downregulation of this survival pathway may result in the induction of apoptosis and decreased cellular proliferation. The activation of IGF-1R, a tyrosine kinase and a member of the insulin receptor family, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been highly implicated in tumorigenesis and metastasis.
An orally available, small-molecule histone deacetylase (HDAC) inhibitor with potential antineoplastic activity. Pracinostat inhibits HDACs, which may result in the accumulation of highly acetylated histones, followed by the induction of chromatin remodeling; the selective transcription of tumor suppressor genes; the tumor suppressor protein-mediated inhibition of tumor cell division; and, finally, the induction of tumor cell apoptosis. This agent may possess improved metabolic, pharmacokinetic and pharmacological properties compared to other HDAC inhibitors.
A synthetic small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Ganetespib binds to and inhibits Hsp90, resulting in the proteasomal degradation of oncogenic client proteins, the inhibition of cell proliferation and the elevation of heat shock protein 72 (Hsp72); it may inhibit the activity of multiple kinases, such as c-Kit, EGFR, and Bcr-Abl, which as client proteins depend on functional HsP90 for maintenance. Hsp90, a 90 kDa molecular chaperone upregulated in a variety of tumor cells, plays a key role in the conformational maturation, stability and function of ""client"" proteins within the cell, many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, transcription factors and hormone receptors. Hsp72 exhibits anti-apoptotic functions; its up-regulation may be used as a surrogate marker for Hsp90 inhibition.
An orally bioavailable inhibitor of Janus kinase 2 (JAK2) and the JAK2 mutant JAK2V617F with potential antineoplastic activity. Oral JAK2 inhibitor SB1518 competes with JAK2 for ATP binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-STAT signaling pathway, and so caspase-dependent apoptosis. JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders; the JAK2V617F gain-of-function mutation involves a valine-to-phenylalanine modification at position 617. The JAK-STAT signaling pathway is a major mediator of cytokine activity.
An orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations.
An orally bioavailable synthetic P2 threonine boronic acid inhibitor of the chymotrypsin-like activity of the proteasome, with potential antineoplastic activity. Delanzomib represses the proteasomal degradation of a variety of proteins, including inhibitory kappaBalpha (IkappaBalpha), resulting in the cytoplasmic sequestration of the transcription factor NF-kappaB; inhibition of NF-kappaB nuclear translocation and transcriptional up-regulation of a variety of cell growth-promoting factors; and apoptotic cell death in susceptible tumor cell populations. In vitro studies indicate that this agent exhibits a favorable cytotoxicity profile toward normal human epithelial cells, bone marrow progenitors, and bone marrow-derived stromal cells relative to the proteasome inhibitor bortezomib. The intracellular protein IkappaBalpha functions as a primary inhibitor of the proinflammatory transcription factor NF-kappaB.
The s-malate salt form of cabozantinib, an orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several RTKs, which are often overexpressed in a variety of cancer cell types, including hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL. This may result in an inhibition of both tumor growth and angiogenesis, and eventually lead to tumor regression.
An anaplastic (malignant) meningioma occurring in adults.
A very rare severe motor neuron disease with manifestation of progressive upper and lower motor neuron degeneration causing facial spasticity, dysarthria, and gait disorders with onset before 25 years of age. The disease is usually slowly progressive and some patients have been reported to become bedridden by 12 to 50 years of age. Mutations in the following genes have been found in patients ALS2 (2q33-q35), and rarely SIGMAR1 (9p13.3), SPG11 (15q13-q15) and FUS (16p11.2).
Familial atrial fibrillation is an inherited abnormality of the heart's normal rhythm. Atrial fibrillation is characterized by episodes of uncoordinated electrical activity (fibrillation) in the heart's upper chambers (the atria), which cause a fast and irregular heartbeat. If untreated, this abnormal heart rhythm (arrhythmia) can lead to dizziness, chest pain, a sensation of fluttering or pounding in the chest (palpitations), shortness of breath, or fainting (syncope). Atrial fibrillation also increases the risk of stroke and sudden death. Complications of atrial fibrillation can occur at any age, although some people with this heart condition never experience any health problems associated with the disorder.
Right coronary artery begins (branches off from) the pulmonary artery rather than as normal from the root of the aorta, above the right cusp of the aortic valve.
An aggressive diffuse large B-cell lymphoma frequently arising in the setting of HIV infection and characterized by the presence of large neoplastic cells resembling B-immunoblasts which have the immunophenotypic profile of plasma cells. Sites of involvement include the oral cavity, sinonasal cavity, skin, soft tissues, gastrointestinal tract, and bone.
An aggressive diffuse large B-cell lymphoma occurring in patients with multicentric type Castleman disease. It is characterized by the presence of human herpesvirus 8-infected large B-lymphocytes that resemble plasmablasts. It is usually seen in patients with HIV infection.
A rare mixed phenotype acute leukemia in which the blasts express B-lymphoid and myeloid lineage markers but are negative for MLL translocation and t(9;22)(q34;q11.2) translocation. The prognosis is usually unfavorable.
SCA36 is a slowly progressive neurodegenerative disorder characterized by adult-onset gait ataxia, eye movement abnormalities, tongue fasciculations, and variable upper motor neuron signs. Some affected individuals may develop hearing loss (summary by Garcia-Murias et al., 2012). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
The oil extracted from the nuts of Gevuina avellana. Hazelnut oil is a good source of vitamin E and is typically used in skincare preparations.
The oil extracted from the fruit of Pistacia vera. Pistachio oil is used as a food oil.
A question about whether an individual feels or felt that their health is excellent.
A recombinant protein comprised of epitopes of the extracellular domains of human vascular endothelial growth factor receptors (VEGFR) fused to the constant region (Fc) of human IgG1 with potential antiangiogenic activity. Afilbercept, functioning as a soluble decoy receptor, binds to pro-angiogenic vascular endothelial growth factors (VEGFs), thereby preventing VEGFs from binding to their endogenous receptors. Disruption of the binding of VEGFs to their cellular receptors may result in the inhibition of tumor angiogenesis, metastasis, and ultimately tumor regression.
Used as a laxative in constipation and various medical conditions, Cascara (cascara sagrada) is dried bark of Picramnia sp. (Simarubaceae) or Rhamnus purshiana (Rhamnaceae) containing stimulant laxative anthranol glycosides that act on the intestinal wall to increase muscle contractions and encourage bowel movements. (NCI04)
A recombinant agent chemically identical to or similar to the endogenous cytokine interleukin-4 (IL-4). Produced primarily by activated T-cells, IL-4 binds to and activates its cell-surface receptor, stimulating the proliferation and differentiation of activated B-cells and enhancing their ability to present antigens to T-cells. As a potential immunotherapeutic agent, recombinant IL-4 also augments the effects of other cytokines on dendritic cells (DC), cytotoxic T lymphocytes (CTL), and tumor-infiltrating lymphocytes (TIL).
Brain-derived neurotrophic factor (247 aa, ~28 kDa) is encoded by the human BDNF gene. This protein plays a role in both the development of the nervous system and neuronal survival.
An extract of the edible mushroom Maitaki, Grifola frondosa, rich in glucan polysaccharides, with potential immunostimulating activity. Upon oral ingestion, Maitaki mushroom extract may promote dendritic cell (DC) maturation, increase interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) production, and may enhance natural killer (NK) cell activity, thereby amplifying both innate and T cell-mediated immune responses against cancer cells. In addition, this extract may stimulate the production of granulocyte colony stimulating factor (GCSF) and promote hematopoiesis, and may improve the neutrophil count.
Herniation of the upper part of the stomach through the diaphragm.
Hypogonadotropic hypogonadism not associated with a deficiency of other pituitary hormones.
Familial multiple lipomatosis is a rare autosomal dominant disorder characterized by numerous encapsulated lipomas on the trunk and extremities (Keskin et al., 2002).
Cone-rod dystrophy (CORD) characteristically leads to early impairment of vision. An initial loss of color vision and of visual acuity is followed by nyctalopia (night blindness) and loss of peripheral visual fields. In extreme cases, these progressive symptoms are accompanied by widespread, advancing retinal pigmentation and chorioretinal atrophy of the central and peripheral retina (Moore, 1992). In many families, perhaps a majority, central and peripheral chorioretinal atrophy is not found (Tzekov, 1998). Genetic Heterogeneity of Autosomal Cone-Rod Dystrophy There are several other autosomal forms of CORD for which the molecular basis is known. CORD3 (604116) is caused by mutation in the ABCA4 gene (601691) on chromosome 1p22. CORD5 (600977) is caused by mutation in the PITPNM3 gene (608921) on chromosome 17p13. CORD6 (601777) is caused by mutation in the GUCY2D gene (600179) on chromosome 17p13.1. CORD7 (603649) is caused by mutation in the RIMS1 gene (606629) on chromosome 6q13. CORD9 (612775) is caused by mutation in the ADAM9 gene (602713) on chromosome 8p11. CORD10 (610283) is caused by mutation in the SEMA4A gene (607292) on chromosome 1q22. CORD11 (610381) is caused by mutation in the RAXL1 gene (610362) on chromosome 19p13. CORD12 (612657) is caused by mutation in the PROM1 gene (604365) on chromosome 4p15. CORD13 (608194) is caused by mutation in the RPGRIP1 gene (605446) on chromosome 14q11. CORD14 (see 602093) is caused by mutation in the GUCA1A gene (600364) on chromosome 6p21. CORD15 (613660) is caused by mutation in the CDHR1 gene (609502) on chromosome 10q23. CORD16 (614500) is caused by mutation in the C8ORF37 gene (614477) on chromosome 8q22. CORD18 (615374) is caused by mutation in the RAB28 gene (612994) on chromosome 4p15. CORD19 (615860) is caused by mutation in the TTLL5 gene (612268) on chromosome 14q24. CORD20 (615973) is caused by mutation in the POC1B gene (614784) on chromosome 12q21. CORD21 (616502) is caused by mutation in the DRAM2 gene (613360) on chromosome 1p13. A diagnosis of CORD was made in an individual with a mutation in the AIPL1 gene (604392.0004) on chromosome 17p13.1, as well as in an individual with a mutation in the UNC119 gene (604011.0001) on chromosome 17q11.2. Other mapped loci for autosomal CORD include CORD1 (600624) on chromosome 18q21.1-q21.3; CORD8 (605549) on chromosome 1q12-q24; and CORD17 (615163) on chromosome 10q26. For a discussion of X-linked forms of cone-rod dystrophy, see CORDX1 (304020).
Anthraquinone glycosides found in senna plant, usually referring to the sennosides A and B, with laxative activity. Sennosides act on and irritate the lining of the intestine wall, thereby causing increased intestinal muscle contractions leading to vigorous bowel movement.
Stuttering is a disorder of the flow of speech characterized by involuntary repetitions or prolongations of sounds or syllables, and by interruptions of speech known as blocks (summary by Raza et al., 2010). Stuttering typically arises in young children, where it affects at least 15% of those in age range 4 to 6 years (Bloodstein, 1995). Stuttering usually resolves spontaneously before adolescence, leading to a population prevalence of 1 to 2% among adults. Stuttering beyond childhood is characterized by a significant bias towards males, with males outnumbering females by a ratio of 3:1 to 5:1 (Yairi et al., 1996). Genetic Heterogeneity of Familial Persistent Stuttering Also see STUT2 (609261), mapped to chromosome 12q24; STUT3 (614655), mapped to chromosome 3q; and STUT4 (614668) mapped to chromosome 16q.
A rare aberrant human behavior involving consumption of excrement.
A syndrome characterized by a smiling or happy facial expression (hence the adjective ""geleophysic"" from Greek gelios, laughing + physis, nature), short stature, brachydactyly, and dysostosis multiplex-like changes in the hands and feet. Infiltration of heart valves and liver with mucopolysaccharide-like substance has been demonstrated in some patients. Mild developmental delay is associated in some cases, but speech retardation may be attributed to hearing problems. Psychomotor retardation is an occasional feature.
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancellation of the vestibulo-ocular reflex.
An indenoisoquinoline and non-camptothecin inhibitor of topoisomerase I (Top I) with potential antineoplastic activity. Topoisomerase I inhibitor LMP400 binds to the topoisomerase I-DNA covalent cleavage complexes, and inhibits repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations. Compared to camptothecins, indenoisoquinolines are chemically stable, produce stable Top I-DNA cleavage complexes, induce unique DNA cleavage sites and appear more resistant to multidrug efflux pumps.
Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immune deficiency characterized by the classic triad of recurrent skin boils, cyst-forming pneumonias, and extreme elevations of serum IgE. It is now recognized that other common manifestations include eczema, mucocutaneous candidiasis, and several connective tissue and skeletal abnormalities. A rash in the newborn period subsequently evolves into an eczematoid dermatitis. Recurrent staphylococcal skin boils and bacterial pneumonias usually manifest in the first years of life. Pneumatocoeles and bronchiectasis often result from aberrant healing of pneumonias. Mucocutaneous candidiasis is common. A characteristic facial appearance typically emerges in adolescence. Skeletal abnormalities include osteopenia, minimal trauma fractures, and scoliosis. Vascular abnormalities include middle-sized artery tortuosity and aneurysms, with infrequent clinical sequelae of myocardial infarction and subarachnoid hemorrhage. Gastrointestinal (GI) manifestations include gastroesophageal reflux disease; esophageal dysmotility; and rarely colonic perforations, some of which are associated with diverticuli. Fungal infection of the GI tract (typically histoplasmosis, Cryptococcus, and Coccidioides) also occur infrequently. Survival is typically into adulthood, but life span is often shortened. Most deaths are associated with Gram-negative (Pseudomonas) or filamentous fungal pneumonias resulting in hemoptysis. Lymphomas occur at an increased frequency.
An orally bioavailable pan-inhibitor of fibroblast growth factor receptor (FGFR) family proteins, with potential antineoplastic activity. Upon oral administration, FGFR inhibitor LY2874455 binds to and inhibits FGFR subtypes 1 (FGFR1), 2 (FGFR2), 3 (FGFR3) and 4 (FGFR4), which results in the inhibition of FGFR-mediated signal transduction pathways. This inhibits both tumor angiogenesis and proliferation of FGFR-overexpressing tumor cells. FGFR, a family of receptor tyrosine kinases upregulated in many tumor cell types, plays a key role in cellular proliferation, cell survival and angiogenesis.
A topical nanoemulsion-based gel formulation containing 5-aminolevulinic acid (ALA), a metabolic precursor of the photosensitizer protoporphyrin IX, with a potential application for enhanced photodynamic therapy (PDT) for various precancerous and malignant skin lesions. After topical administration of a thick layer of the ALA-based BF-200 gel formulation to the affected area, ALA penetrates the skin and is intracellularly converted to protoporphyrin IX (PpIX). Exposure of PpIX to the proper excitation wavelength of light generates singlet oxygen molecules, resulting in a local cytotoxic effect.
A recombinant, long-acting analog of human insulin, with blood glucose-lowering activity. Upon subcutaneous injection, insulin degludec forms a multi-hexameric depot from which insulin monomers are slowly released into the systemic circulation. Insulin regulates glucose metabolism by binding to insulin receptors on muscle and fat cells, which stimulates the cellular uptake of glucose and lowers blood glucose levels. Insulin inhibits the liver's conversion of stored glycogen into glucose, which also contributes to lower blood glucose levels. In addition, insulin inhibits lipolysis in adipose tissue, inhibits proteolysis, and enhances protein synthesis. Insulin degludec doesn't contain the amino acid threonine that is found at position B30 in human insulin; additionally, the lysine at position B29 is conjugated to hexadecanedioic acid, which allows the formation of the multi-hexamers upon subcutaneous injection. The phenol and zinc present in the pharmaceutical formulation promote a di-hexameric state of insulin degludec.
An orally bioavailable inhibitor of the nonstructural protein 3 (NS3), with potential activity against hepatitis C virus (HCV). Upon administration, asunaprevir binds to the active center of the HCV NS3 and prevents NS3 protease-mediated polyprotein maturation. This disrupts the processing of viral proteins required for HCV replication. NS3, a serine protease, is essential for the proteolytic cleavages within the HCV polyprotein and plays a key role during HCV viral RNA replication. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family.
An orally bioavailable, specific inhibitor of histone deacetylase 6 (HDAC6) with potential antineoplastic activity. Ricolinostat selectively targets and binds to HDAC6, thereby disrupting the Hsp90 protein chaperone system through hyperacetylation of Hsp90 and preventing the subsequent aggresomal protein degradation. This leads to an accumulation of unfolded and misfolded ubiquitinated proteins and may eventually induce cancer cell apoptosis, and inhibition of cancer cell growth. HDAC6, a class II HDAC deacetylase located in the cytoplasm, appears to play a key role in the formation and activation of the aggresomes needed for degradation of misfolded proteins. Compared to non-selective HDAC inhibitor, ACY-1215 is able to reduce the toxic effects on normal, healthy cells.
An orally bioavailable phytoestrogen-rich Traditional Chinese Medicine (TCM) containing extracts from the six herbs Herba epimedii, Radix dipsaci (Dipsacus root), Radix salvia miltiorrhiza (Salvia root, Danshen, red sage root), Rhizoma anemarrhenae (zhi Mu), Fructus Psoraleae (fruit of Psoralea corylifolia L), and Radix Rehmanniae (Rehmannia root, Rehmannia glutinosa, Sheng Di Huang, Rehmannia glutinosa Libosch), with potential anti-osteoporotic and bone-strengthening activities. Xianling gubao (XLGB) contains various phytochemicals, including flavonoids, coumarins, saponins, alkaloids and terpenes. Upon oral administration of XLGB, the active ingredients may strengthen bones and may treat or prevent osteoporosis, osteoarthritis, bone loss and bone fractures.
Resistance to thyroid-stimulating hormone (TSH; see 188540), a hallmark of congenital nongoitrous hypothyroidism, causes increased levels of plasma TSH and low levels of thyroid hormone. Only a subset of patients develop frank hypothyroidism; the remainder are euthyroid and asymptomatic (so-called compensated hypothyroidism) and are usually detected by neonatal screening programs (Paschke and Ludgate, 1997). Genetic Heterogeneity of Congenital Nongoitrous Hypothyroidism CHNG2 (218700) is caused by mutation in the PAX8 gene (167415) on chromosome 2q12-q14; CHNG3 (609893) maps to a locus on chromosome 15q25.3; CHNG4 (275100) is caused by mutation in the TSHB gene (188540) on chromosome 1p13; CHNG5 (225250) is caused by mutation in the NKX2-5 gene (600584) on chromosome 5q34; and CHNG6 (614450) is caused by mutation in the THRA gene (190120) on chromosome 17q21.1.
The state of being uncertain about future access to nutritionally adequate and affordable foods.
Immunoglobulins obtained from human serum for the purpose of intravenous administration.
Reduced activity of coagulation factor VIII. Factor VIII (fVIII) is a cofactor in the intrinsic clotting cascade that is activated to fVIIIa in the presence of minute quantities of thrombin. fVIIIa acts as a receptor, for factors IXa and X.
A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.
Compounds that either stimulate the opening or prevent closure of VOLTAGE-GATED SODIUM CHANNELS.
A subclass of sodium channel blockers that are specific for ACID-SENSING SODIUM CHANNELS.
A subclass of sodium channel blockers that are specific for EPITHELIAL SODIUM CHANNELS.
Live vaccines prepared from microorganisms without their virulence altered. Examples include smallpox (vaccinia) and adenovirus vaccines.
Clinical or physiological indicators that precede the onset of disease.
Compounds that either stimulate the opening or prevent closure of EPITHELIAL SODIUM ION CHANNELS.
A form of elephantiasis caused by soil particles which penetrate the skin of the foot. It is limited to tropical regions with soils of high volcanic content.
An abnormality of the jaws or teeth affecting the contour of the face. Such abnormality could be acquired or congenital.
A physical misalignment of the upper (maxilla) and lower (mandibular) jaw bones in which either or both recede relative to the frontal plane of the forehead.
The formation of dense connective tissue in the TYMPANIC MEMBRANE that does not necessarily cause or lead to loss of hearing.
Compounds that interact with and modulate the activity of CANNABINOID RECEPTORS.
A proprietary compound targeting cell cycle checkpoint kinase 1 (chk1) with potential chemopotentiation activity. Chk1 inhibitor PF-477736 inhibits chk1, an ATP-dependent serine-threonine kinase that is a key component in the DNA replication-monitoring S/G2 checkpoint system. By overriding the last checkpoint defense against DNA damaging agent-induced lethal damage, chk1 inhibitor PF-477736 may potentiate the antitumor efficacy of various chemotherapeutic agents against tumor cells with intrinsic checkpoint defects.
Flattest corneal meridian defined as the axis in degrees wherein power is least and radius of curvature is longest.
Refractive power of the cornea at the flattest meridian defined as least power measured in diopters, and longest radius of curvature measured in mm.
Steepest corneal meridian defined as the axis in degrees wherein power is greatest and radius of curvature is shortest.
A rare functional disorder with recurrent episodes of torticollis posturing of the head (inclination or tilting of the head to one side) in healthy children. The prevalence is unknown and the benign nature of the disorder probably means that it is under reported. Onset occurs within the first year of life with episodes occurring between every few weeks and every few months. The duration of the torticollis varies between patients, but usually lasts from a few hours to a few days. The frequency and duration of the torticollis episodes decrease as the patient gets older and episodes usually stop completely by 5 years of age. The disorder usually occurs sporadically, but familial occurrence has been reported.
A congenital out pouching of the bladder involving the ureteral hiatus.
A very rare severe form of epilepsy with poor prognosis that usually begins within a few weeks of birth. The seizure activity can appear in multiple locations in the brain or migrate from one region to another during an episode. It results in severe developmental delay.
A monovalent cation that is metabolized much like sodium and is important in many cellular functions inside or on the surface of cells.
A rare, benign, slow growing, multifocal, and expansile lesion of the jaws. Both familiar and sporadic cases have been reported. It is characterized by a fibroblastic proliferation, cementum, and limited bone formation.
Craniofacial microsomia (CFM) includes a spectrum of malformations primarily involving structures derived from the first and second branchial arches. Characteristic findings include facial asymmetry resulting from maxillary and/or mandibular hypoplasia; preauricular or facial tags; ear malformations that can include microtia (hypoplasia of the external ear), anotia (absence of the external ear), or aural atresia (absence of the external ear canal); and hearing loss. Severity can range from subtle facial asymmetry with a small skin tag in front of an otherwise normal-appearing ear to bilateral involvement (typically asymmetric), microtia/anotia with atresia of the ear canals, microphthalmia, and respiratory compromise from severe mandibular hypoplasia. Other craniofacial malformations including cleft lip and/or palate can be seen. Non-craniofacial malformations, especially vertebral, renal, cardiac, and limb, can be seen.
Derivatives of BENZOIC ACID that contain one or more amino groups attached to the benzene ring structure. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the aminobenzoate structure.
Hyperhomocysteinemia refers to above-normal concentrations of plasma/serum homocysteine. Plasma/serum homocysteine is the sum of the thiol-containing amino acid homocysteine and the homocysteinyl moiety of the disulfides homocystine and cysteine-homocysteine, whether free or bound to proteins (Malinow and Stampfer, 1994). Hyperhomocysteinemia in isolation may be associated with an increased risk of atherosclerosis and recurrent arterial and venous thrombosis usually in the third or fourth decade of life (review by Welch and Loscalzo, 1998). Homocysteinemia is also a feature of several inherited metabolic disorders, including homocystinuria (236200), due to mutation in the CBS gene (613381), and N(5,10)-methylenetetrahydrofolate reductase deficiency (236250), caused by mutation in the MTHFR gene (607093). Homocysteinemia/homocystinuria and megaloblastic anemia can result from defects in vitamin B12 (cobalamin; cbl) metabolism, which have been classified according to complementation groups of cells in vitro; see cblE (236270) and cblG (250940). See also the various forms of combined methylmalonic aciduria (MMA) and homocystinuria due to disorders of cobalamin: cblC (277400), cblD (277410), and cblF (277380).
Fanconi-Bickel syndrome is a rare but well-defined clinical entity, inherited in an autosomal recessive mode and characterized by hepatorenal glycogen accumulation, proximal renal tubular dysfunction, and impaired utilization of glucose and galactose (Manz et al., 1987). Because no underlying enzymatic defect in carbohydrate metabolism had been identified and because metabolism of both glucose and galactose is impaired, a primary defect of monosaccharide transport across the membranes had been suggested (Berry et al., 1995; Fellers et al., 1967; Manz et al., 1987; Odievre, 1966). Use of the term glycogenosis type XI introduced by Hug (1987) is to be discouraged because glycogen accumulation is not due to the proposed functional defect of phosphoglucomutase, an essential enzyme in the common degradative pathways of both glycogen and galactose, but is secondary to nonfunctional glucose transport.
The most common form of leishmaniasis that is transmitted through the bite of female phlebotomine sand flies or after exposure to leishmania parasites. It is characterized by skin lesions at the site of insect bite which typically develop within weeks or months after exposure. The lesions typically progress from small papules to open sores with raised borders and central ulcers which can be covered with scales or crust.
Pain felt as if it were arising in an absent or amputated limb, organ or body part.
Pneumonia caused by the parasite Toxoplasma gondii. It usually presents as an opportunistic infection in immunocompromised patients, especially patients with AIDS. It is rare in immunocompetent individuals. Signs and symptoms include cough, fever, and dyspnea.
Any vaccine that contains an inactivated toxic substance used for disease prophylaxis or to vaccinate against snake bites.
A trichothiodystrophy syndrome (sulfur-deficient brittle hair), short stature, mental deficiency poor sexual maturation, and infertility originally observed in the Amish kindred. This syndrome has the main characteristics of Tay syndrome (brittle hair, impaired intelligence, decreased fertility, and short stature), except for ichthyosis. Originally observed in an Amish family (hence its name) in Indiana, the syndrome was later reported in other groups, including a Moroccan family.
Axenfeld anomaly (defect of the peripheral segment of the eye) and Rieger anomaly (defect of the anterior segment of the eye) associated with variable craniofacial abnormalities, abnormal dentition, dysplastic oculomotor muscles, hydrocephalus, hypertelorism, facial or abducent palsy, and mental retardation.
Acrorenal syndrome comprises a wide spectrum of congenital malformation disorders with characteristics of the co-occurrence of distal limb anomalies (usually bilateral cleft feet and/or hands) and renal defects (for example unilateral or bilateral agenesis), that can be associated with a variety of other anomalies such as those of genitourinary tract, abdominal well defects, intestinal atresia and lung malformations. Familial cases have been reported in which an autosomal recessive inheritance was suspected.
Heterotaxy ('heter' meaning 'other' and 'taxy' meaning 'arrangement'), or situs ambiguus, is a developmental condition characterized by randomization of the placement of visceral organs, including the heart, lungs, liver, spleen, and stomach. The organs are oriented randomly with respect to the left-right axis and with respect to one another (Srivastava, 1997). Heterotaxy is a clinically and genetically heterogeneous disorder. For a discussion of genetic heterogeneity of visceral heterotaxy, see HTX1 (306955).
A rare autosomal recessive metabolic disorder caused by mutation in CNDP1 gene. It is characterized by deficiency of carnosinase and manifests with severe mental defects and myoclonic seizures.
An increased concentration of carnosine in the urine.
A group of chronic, inflammatory childhood disorders of unknown etiology that primarily involve joints.
Chronic kidney damage due to vesicoureteral reflux.
An extremely rare lethal autosomal recessive disorder characterised by massive birth weight, swollen globular body, generalised oedema, short limbs, postaxial polydactyly, thick skin, facial dysmorphism, excessive connective tissue, renal dysplasia, and in some patients, organomegaly, craniosynostosis with acrocephaly, omphalocele, cleft palate, and cryptorchidism. Fewer than 10 cases have been reported to date.
Thyroglossal duct cysts are common benign cervical masses. They represent a remnant of the thyroglossal duct that fails to regress during fetal development. Nearly all cases present sporadically in young children as slowly enlarging midline neck mass (summary by Greinwald et al., 1996).
A 6-maleimidocaproyl hydrazone derivative prodrug of the anthracycline antibiotic doxorubicin (DOXO-EMCH) with antineoplastic activity. Following intravenous administration, aldoxorubicin binds selectively to the cysteine-34 position of albumin via its maleimide moiety. Doxorubicin is released from the albumin carrier after cleavage of the acid-sensitive hydrazone linker within the acidic environment of tumors and, once located intracellularly, intercalates DNA, inhibits DNA synthesis, and induces apoptosis. Albumin tends to accumulate in solid tumors as a result of high metabolic turnover, rapid angiogenesis, hypervasculature, and impaired lymphatic drainage. Because of passive accumulation within tumors, this agent may improve the therapeutic effects of doxorubicin while minimizing systemic toxicity.
Granulomatosis with polyangiitis, formerly termed Wegener granulomatosis, is a systemic disease with a complex genetic background. It is characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract, glomerulonephritis, vasculitis, and the presence of antineutrophil cytoplasmatic autoantibodies (ANCAs) in patient sera. These ANCAs are antibodies to a defined target antigen, proteinase-3 (PR3, PRTN3; 177020), which is present within primary azurophil granules of neutrophils (PMNs) and lysozymes of monocytes. On cytokine priming of PMNs, PR3 translocates to the cell surface, where PR3-ANCAs can interact with their antigens and activate PMNs. PMNs from patients with active GPA express PR3 on their surface, produce respiratory burst, and release proteolytic enzymes after activation with PR3-ANCAs. The consequence is a self-sustaining inflammatory process (Jagiello et al., 2004).
A focus of subchorial thrombus variably extending into the intervillous space, often with peripheral villous compression. The clot may be wholly or minimally laminated reflecting age.
A syndrome that occurs in a proportion of patients with HIV infection and Kaposi sarcoma after initiation of highly active antiretroviral therapy. It is characterized by a deterioration in their clinical status, despite control of virologic and immunologic parameters.
A category of juvenile idiopathic arthritis associated with arthritis and enthesitis, which may involve the axial skeleton. It is a form of juvenile spondyloarthritis.
A term that refers to a vascular lesion characterized by an extracellular lipid pool with intimal smooth muscle cell loss typically adjacent to the medial wall in addition to varying degrees of macrophage infiltration near the lumen. (Arteriosclerosis, Thrombosis, and Vascular Biology. 2007; 27:986-989)
Fatty acid hydroxylase-associated neurodegeneration (FAHN) is characterized early in the disease course by central nervous system involvement including corticospinal tract involvement (spasticity), mixed movement disorder (ataxia/dystonia), and eye findings (optic atrophy, oculomotor abnormalities), and later in the disease course by progressive intellectual impairment and seizures. With disease progression, dystonia and spasticity compromise the ability to ambulate, leading to wheelchair dependence. Life expectancy is variable. FAHN is considered to be a subtype of neurodegeneration with brain iron accumulation (NBIA).
Nephrotic syndrome for which no cause has been identified.
Blockage of the lumen of the inferior vena cava.
An orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. Through a mechanism that is reported to be different from other approved AR antagonists, enzalutamide inhibits the activity of prostate cancer cell ARs, which may result in a reduction in prostate cancer cell proliferation and, correspondingly, a reduction in the serum prostate specific antigen (PSA) level. AR over-expression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance.
The essential oil of Origanum vulgare. Oregano oil has antibacterial and antifungal properties.
A plant whose seeds and root have been used in some cultures to treat certain medical problems. It may have antioxidant effects. The scientific name is Arctium lappa.
An orally available inhibitor of epidermal growth factor receptor (EGFR), FMS-related tyrosine kinase 3 (FLT3, STK1, CD135 or FLK2), and the non-receptor tyrosine kinase ABL (Abl), with potential antineoplastic activity. Upon administration, the EGFR/FLT3/Abl inhibitor SKLB1028 specifically binds to and inhibits EGFR, FLT3 and Abl, which interferes with the activation of EGFR-, FLT3- and Abl-mediated signal transduction pathways and reduces cell proliferation in cancer cells that overexpress EGFR, FLT3 and/or Abl. EGFR, EGFR and Abl are all overexpressed in a variety of cancers and play key roles in tumor cell proliferation.
An orally bioavailable imidazoquinoline targeting the phosphatidylinositol 3 kinase (PI3K) and the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. Dactolisib inhibits PI3K kinase and mTOR kinase in the PI3K/AKT/mTOR kinase signaling pathway, which may result in tumor cell apoptosis and growth inhibition in PI3K/mTOR-overexpressing tumor cells. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K.
An orally bioavailable, small-molecule inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon oral administration, ibrutinib binds to and irreversibly inhibits BTK activity, thereby preventing both B-cell activation and B-cell-mediated signaling. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is required for B cell receptor signaling, plays a key role in B-cell maturation, and is overexpressed in a number of B-cell malignancies. The expression of BTK in tumor cells is also associated with increased proliferation and survival.
The acetate form of the 21-substituted-19-nor-progestin telapristone, an orally available selective progesterone receptor modulator (SPRM), with potential anti-progesterone and antineoplastic activities. Upon oral administration, CDB-4124 competitively binds to the progesterone receptor (PR) in progesterone-responsive tissue and inhibits PR-mediated gene expression. This interferes with progesterone activity in the reproductive system. As a result, this agent may suppress ovulation and inhibit proliferation of endometrial tissue. Also, this agent may prevent cell growth and induce apoptosis in estrogen receptor (ER) and PR-positive breast cancer cells through a reduction in progesterone levels, ER downregulation and a suppression of the expression of cyclin-dependent kinases (CDK) 2 and 4, ultimately leading to G1/S cell cycle arrest. Unlike some other SPRMs, this agent does not exert any estrogenic, androgenic, anti-estrogenic, and anti-androgenic activities.
A rare autosomal recessive inherited nephrotic syndrome that is present in the first week of life. It manifests with edema and proteinuria and usually has a poor prognosis.
Autosomal dominant limb-girdle muscular dystrophy type 1D (LGMD1D) is a subtype of autosomal dominant limb-girdle muscular dystrophy characterized by an adult-onset of slowly progressive, proximal pelvic girdle weakness, with none, or only minimal, shoulder girdle involvement, and absence of cardiac and respiratory symptoms. Mild to moderate elevated creatine kinase serum levels and gait abnormalities are frequently observed.
Myopathic mitochondrial DNA (mtDNA) depletion syndrome is one of the main forms of mtDNA depletion syndrome (see this term) that displays a broad phenotypic spectrum but that is most often characterized by hypotonia, proximal muscle weakness, facial and bulbar weakness and failure to thrive.
An orally bioavailable inhibitor of the serine protease dipeptidyl peptidase 4 (DPP-4), with hypoglycemic and potential renoprotective activities. Upon administration, gemigliptin binds to DPP-4 and inhibits the breakdown of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This prolongs incretin activity, increases postprandial insulin secretion from pancreatic beta cells, decreases glucagon secretion, delays gastric emptying and lowers blood glucose levels. In addition, gemigliptin exerts a renoprotective effect, probably through enhanced GLP-1 signaling, may prevent apoptosis and acute kidney injury induced by nephrotoxic agents, and may protect against diabetic nephropathy.
Disease with characteristics of progressive ataxia beginning during infancy, a pyramidal syndrome and dental agenesis. The syndrome has been described in four children born to consanguineous parents. The mode of transmission is autosomal recessive.
Syndrome caused by impairment of mitochondria. Whilst mitochondrial disorders may be caused by impairment of a single stage of energy production, individuals with multiple mitochondrial dysfunctions syndrome have reduced function of more than one stage. Symptoms begin in early life and affected individuals usually do not live past infancy. Symptoms include encephalopathy, hypotonia, seizures and psychomotor delay. Most affected babies have lactic acidosis that can be life threatening.
Yellow coloring of skin, mucous membranes and eyes in an otherwise healthy breast-fed newborn due to insufficient intake of maternally-expressed milk. It commonly appears four to seven days after birth.
A rare ectodermal dysplasia syndrome characterised by severe generalised hypotrichosis, parietal alopecia, secondary anodontia resulting from enamel hypoplasia, onychodystrophy, bone deficiency in the frontoparietal region and skin manifestations (including naevus pigmentosus, papules, ephelides, palmoplantar keratosis, supernumerary nipples, abnormal dermatoglyphics). There have been no further descriptions in the literature since 1983.
X-linked mental retardation with characteristics of Brain anomalies, severe mental Retardation, Ectodermal dysplasia, Skeletal deformities (vertebral anomalies, scoliosis, polydactyly), Ear/eye anomalies (maldevelopment, small optic nerves, low set and large ears with hearing loss) and Kidney dysplasia/hypoplasia (giving the acronym BRESEK syndrome). It has been described in two brothers, one of whom died shortly after birth. One of the brothers also had Hirschsprung disease and Cleft palate/cryptorchidism (giving the acronym: BRESHECK syndrome). Transmission is X-linked dominant.
A manganese-based non-peptidyl mimetic of the human mitochondrial manganese superoxide dismutase (MnSOD), with potential antioxidant and chemo/radioprotective activities. Upon administration, imisopasem manganese mimics the activity of MnSOD and scavenges reactive oxygen species (ROS), such as superoxide anion, which prevents oxygen free radical damage to macromolecules such as DNA. This reduces ROS-mediated lipid peroxidation, prevents apoptosis and protects against oxygen free radical-induced toxicity in normal tissues.
An orally available v-raf murine sarcoma viral oncogene homolog B1 (B-raf) serine/threonine protein kinase inhibitor with potential antineoplastic activity. CEP-32496 specifically and selectively inhibits the activity of the mutated form (V600E) of B-raf kinase. This inhibits the activation of the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway and may result in a decrease in the proliferation of tumor cells expressing the mutated B-raf gene. The Raf mutation BRAF V600E, in which valine is substituted for glutamic acid at residue 600, is frequently found in a variety of human tumors and results in the constitutive activation of the RAF/MEK/ERK signaling pathway that regulates cellular proliferation and survival.
Genetic epilepsy with febrile seizures plus (GEFS+) is a spectrum of seizure disorders of varying severity. GEFS+ is usually diagnosed in families whose members have a combination of febrile seizures, which are triggered by a high fever, and recurrent seizures (epilepsy) of other types, including seizures that are not related to fevers (afebrile seizures). The additional seizure types usually involve both sides of the brain (generalized seizures); however, seizures that involve only one side of the brain (partial seizures) occur in some affected individuals. The most common types of seizure in people with GEFS+ include myoclonic seizures, which cause involuntary muscle twitches; atonic seizures, which involve sudden episodes of weak muscle tone; and absence seizures, which cause loss of consciousness for short periods that appear as staring spells.The most common and mildest feature of the GEFS+ spectrum is simple febrile seizures, which begin in infancy and usually stop by age 5. When the febrile seizures continue after age 5 or other types of seizure develop, the condition is called febrile seizures plus (FS+). Seizures in FS+ usually end in early adolescence.A condition called Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI) is often considered part of the GEFS+ spectrum and is the most severe disorder in this group. Affected infants typically have prolonged seizures lasting several minutes (status epilepticus), which are triggered by fever. Other seizure types, including afebrile seizures, begin in early childhood. These types can include myoclonic or absence seizures. In Dravet syndrome, these seizures are difficult to control with medication, and they can worsen over time. A decline in brain function is also common in Dravet syndrome. Affected individuals usually develop normally in the first year of life, but then development stalls, and some affected children lose already-acquired skills (developmental regression). Many people with Dravet syndrome have difficulty coordinating movements (ataxia) and intellectual disability.Some people with GEFS+ have seizure disorders of intermediate severity that may not fit into the classical diagnosis of simple febrile seizures, FS+, or Dravet syndrome.Family members with GEFS+ may have different combinations of febrile seizures and epilepsy. For example, one affected family member may have only febrile seizures, while another also has myoclonic epilepsy. While GEFS+ is usually diagnosed in families, it can occur in individuals with no history of the condition in their family.
A humanized IgG4 monoclonal antibody that targets the human leukocyte antigen HLA-DR, with potential antineoplastic activity. Upon administration, anti-HLA-DR monoclonal antibody IMMU-114 binds to HLA-DR on HLA-DR-expressing tumor cells and, although the exact mechanism has yet to be fully elucidated, appears to induce hyperactivation of ERK- and JNK-dependent mitogen activated protein kinase signaling pathways. This may lead to mitochondrial membrane depolarization and reactive oxygen species (ROS) generation. This eventually leads to an induction of tumor cell apoptosis and a reduction in tumor cell proliferation. IMMU-14 may be beneficial in the treatment of graft versus host disease (GVHD) as it appears to suppress T-lymphocyte proliferation and natural killer (NK) cell activation. As the Fc region of the orgnial IgG1 MoAb was replaced with the IgG4 isotype, IMMU-114 does not induce a complement cytotoxicity (CDC) or an antibody-dependent cell-mediated cytotoxicity (ADCC). HLA-DR, a MHC class II molecule, is found on various b-cell hematologic malignancies and in autoimmune diseases as well as on normal cells.
A water-soluble, folate-receptor-targeted conjugate of folate and the vinca alkaloid desacetylvinblastine monohydrazide (DAVLBH) with potential antineoplastic activity. The folate moiety of vintafolide binds to folic acid receptors on the tumor cell surface and the agent is internalized via folate receptor-mediated endocytosis, delivering the tubulin-binding DAVLBH moiety directly into the tumor cell; DAVLBH binding to tubulin results in the disruption of microtubule assembly-disassembly dynamics, cell cycle arrest, and tumor cell apoptosis. Folic acid receptors are frequently upregulated on the surfaces of many tumor cell types. DAVLBH is a derivative of the natural product vinblastine.
A tree native to China. Substances taken from the leaves and seeds have been used in some cultures to treat certain medical problems. Maidenhair tree has been studied in the prevention and treatment of Alzheimer disease, dementia, certain blood vessel diseases, and memory loss. It may cause bleeding or high blood pressure when used with certain drugs.
Myelomeningocele that occurs in the region L1 to L3.
Myelomeningocele that occurs in the region L4 to L5.
A type of transposition of the great arteries (TGA) in which aorta is in front of and primarily to the right of the pulmonary artery. This is the most common kind of TGA.
A pregnancy involving two fetuses that share both the chorion and amniotic sac. These twins are invariably identical.
The left common carotid artery has a common origin with the innominate artery.
The left common carotid artery normally originates from the aortic arch. This term refers to an origin of this artery from the brachiocephalic artery. [PMID:18694519]
Fetal choroid plexus cysts (CPCs) are sonographically discrete, small cysts (3 mm or more) found in the choroid plexus within the lateral cerebral ventricles of the developing fetus at 14 to 24 weeks gestation. Imaging of the choroid plexus is performed in the transverse plane of the fetal head at the same level that the lateral cerebral ventricle is evaluated. The choroid plexus should be inspected bilaterally for the presence of cysts. The size of CPCs is not of clinical relevance (pmid:16100637).
Impaction of ulnar head against the triangular fibrocartilage complex and ulnar carpus resulting in progressive degeneration of those structures.
A neoplastic ductal proliferative lesion of the breast characterized by the formation of secondary lumens and prominent intraductal proliferation of a heterogeneous cellular population that may include epithelial cells, myoepithelial cells, or metaplastic apocrine cells.
An immune or non-immune mediated pathological process that represents the underlying mechanism of hypersensitivity conditions.
A type of immune mediated hypersensitivity process that represents the underlying mechanism of allergic conditions.
A type of allergic process that results in an immune response to a foreign antigen.
An abnormal communication between the skin and the oral cavity.
The disposition to develop an allergic or pseudoallergic reaction, the reaction itself or its consequences.
Undertaking cruise travel in the sufficiently recent past to be relevant to a current health issue.
Attempting to persuade or coerce one's child in ways that are not suitable or proper in the circumstances.
A moderate delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts.
A mild delay in the acquisition of the ability to use language to communicate needs, wishes, or thoughts.
Mixed dementia is the co-occurrence of Alzheimer disease and cerebrovascular disease.
A moderate delay in the acquisition of the ability to understand the speech of others.
A severe delay in the acquisition of the ability to understand the speech of others.
A mild delay in the acquisition of the ability to understand the speech of others.
Noroviruses are a group of related viruses. Infection with these viruses causes an illness called gastroenteritis, an inflammation of the stomach and intestines. It can spread from person to person, or through contaminated food or water. You can also get it if you touch a contaminated surface. Norovirus can be serious, especially for young children and older adults. The most common symptoms of norovirus infection are. -Diarrhea. -Nausea and vomiting. -Stomach pain. Other symptoms may include fever, headache or body aches. Treatment includes bed rest and lots of liquids to prevent dehydration. There is no specific medicine to treat norovirus infections. Proper hand washing and safe food preparation may help prevent infections. Centers for Disease Control and Prevention.
The calcium salt form of diethylene triamine pentaacetate (Ca-DTPA or pentetate calcium) with chelating activity. Upon administration, Ca-DTPA loses the Ca ion to form stable chelates with metal ions because DTPA has a higher affinity for heavy metal ions than for Ca ions. Specifically, this agent is able to bind to and form strong complexes with radioactive plutonium, americium, and cerium after internal contamination. The formation of these heavy metal chelates enhances radionuclide excretion.
An electrocardiographic finding of pathologic Q waves with accompanying ST elevation in leads V5, V6, I and aVL, which is suggestive of acute myocardial infarction of the lateral wall of the left ventricle. (CDISC)
The presence of developmental dysplasia of the kidney.
An abnormal production of growth hormone.
A numerical chromosomal abnormality characterized by the presence of three complete sets of chromosomes.
A congenital abnormality in the lumbar region of the spine, in which the spinal cord and meninges protrude through a defect in the spinal column. The protrusion is above the skin surface.
A congenital abnormality in the thoracic region of the spine, in which the spinal cord and meninges protrude through a defect in the spinal column. The protrusion is above the skin surface.
A congenital abnormality in the cervical region of the spine in which the spinal cord and meninges protrude through a defect in the spinal column. The protrusion is above the skin surface.
A rare congenital cardiovascular abnormality in which the aorta arises from the right ventricle and the pulmonary artery arises from the left ventricle.
An electrocardiographic finding of pathologic Q waves in leads V3 and V4, which is suggestive of myocardial infarction of the anterior wall of the left ventricle. (CDISC)
Increased white blood cell count and increased neutrophil precursors resembling leukemia in a neonate or fetus. Often, this is a response to medications received, infection or Down syndrome.
An ester of alkane sulfonic acid that acts as an alkylating agent.
Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery.
A spectrum of malignant tumors, affecting mostly males under age 20, characterized morphologically by the presence of small round cells. Ewing sarcoma and peripheral primitive neuroectodermal tumor represent the ends of a spectrum, with Ewing sarcoma lacking evidence of neural differentiation and the markers that characterize the peripheral primitive neuroectodermal tumor. Ewing sarcoma and peripheral primitive neuroectodermal tumor may share cytogenetic abnormalities, proto-oncogene expression, cell culture and immunohistochemical abnormalities. These tumors may occur in the soft tissues or the bones. Pain and the presence of a mass are the most common clinical symptoms.
Prion diseases, also termed transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative diseases that affect humans and a number of other animal species. The etiology of these diseases is thought to be associated with the conversion of a normal protein, PrPC, into an infectious, pathogenic form, PrPSc. The conversion is induced by prion infections (for example, variant Creutzfeldt-Jakob disease (vCJD), iatrogenic CJD, Kuru), mutations (familial CJD, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia (FFI)) or unknown factors (sporadic CJD (sCJD)), and is thought to occur after PrPC has reached the plasma membrane or is re-internalized for degradation. The PrPSc form shows greater protease resistance than PrPC and accumulates in affected individuals, often in the form of extracellular plaques. Pathways that may lead to neuronal death comprise oxidative stress, regulated activation of complement, ubiquitin-proteasome and endosomal-lysosomal systems, synaptic alterations and dendritic atrophy, corticosteroid response, and endoplasmic reticulum stress. In addition, the conformational transition could lead to the lost of a beneficial activity of the natively folded protein, PrPC.
A chemotherapy compound that contains a platinum atom. Platinum compounds do not contain alkyl groups but do cause DNA crosslinks and adducts similar to alkylating agents. DNA crosslinks and adducts ultimately lead to the induction of apoptosis.
A humanized monoclonal IgG1 antibody directed against the vitronectin receptor alpha v beta 3 integrin. Humanized monoclonal antibody LM609 blocks the binding of ligands, such as vitronectin, to alpha v beta 3 integrin, resulting in inhibition of angiogenesis and metastasis. Alpha v beta 3 integrin is a cell adhesion and signaling receptor that is expressed on the surface of tumor vessel endothelial cells, some tumor cells, and a number of other cell types. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38491&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=38491&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C38723"" NCI Thesaurus)
A hereditary disorder characterized by HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; renal defects in phosphate reabsorption and vitamin D metabolism; and growth retardation. Autosomal and X-linked dominant and recessive variants have been reported.
An orally bioavailable fluoropyrimidine antagonist composed of tegafur combined with two modulators of 5-fluorouracil (5-FU) activity, gimeracil and potassium oxonate, in a molar ratio of 1:0.4:1. Tegafur is a prodrug of 5-fluorouracil, an antimetabolite that inhibits thymidylate synthase, DNA synthesis and cell division, and competes with uridine triphosphate, thus inhibiting RNA and protein synthesis. Gimeracil is a reversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. Potassium oxonate preferentially localizes in the gut and inhibits the enzyme orotate phosphoribosyl-transferase (OPRT), thereby decreasing activation of 5-FU in the gut and activated 5-FU-related gastrointestinal toxicity.
An electrocardiographic finding of pathologic Q waves with accompanying ST elevation in leads III, aVF and often II, which is suggestive of acute myocardial infarction of the inferior wall of the left ventricle. (CDISC)
A mustard agent containing nitrogen and chlorine atoms.
An electrocardiographic finding of an injury in leads corresponding to the anatomic region of the inferolateral wall of the heart.
Tubulin Interaction involves temporary non-covalent binding through intermolecular physical forces of attraction with highly conserved globular alpha, beta, or gamma tubulin protein subunits of microtubules.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 18 in somatic cells.
A hair-containing cyst or sinus usually in the coccygeal region.
A finding indicating a deficiency or excess in biological absorption or assimilation of iodine.
Any process in which the tripeptide hormone prothyroliberin is released from the hypothalamus, processed and bound to receptors in the anterior pituitary, resulting in sustained release of prolactin from the anterior pituitary. Thyroliberin may be elevated in primary hypothyroidism, resulting in elevated prolactin secretion. This process is involved in regulating the levels of both prolactin and thyroid-stimulating hormone.
Enzyme Interaction involves temporary non-covalent binding, typically through intermolecular physical forces of attraction and spatial complementarity, between a molecular entity and biological molecules, usually proteins, that possess catalytic activity.
Active Transporter Interaction involves temporary non-covalent binding of a molecule through intermolecular physical forces of attraction with a protein that, after conformational change, moves a bound substrate across a cell membrane with (symport) or against (antiport) a concentration gradient resulting directly from the expenditure of energy.
A substance with a structure similar to a nucleoside molecule that is capable of occupying the active catalytic site of a reverse transcriptase resulting in inhibition of enzyme function, chain termination, and inhibition of viral replication. These compounds are converted to their active phosphorylated forms by cellular kinases.
A substance structurally unlike a nucleoside molecule that is capable of inhibiting the function of a reverse transcriptase. These compounds do not bind to the active site of the polymerase but in a less conserved pocket near the active site, causing a distortion in the shape of the active site and resulting in inhibition of enzymatic function, chain termination, and inhibition of viral replication.
Free Radical Scavenging involves interference with, or restraint of, production, by ready combination with, chemically unstable, short half-life and highly reactive molecules carrying at least one unpaired or 'free' electron in the outermost electron shell. Appropriating electron(s) from a nearby molecule and damaging that molecule by altering the electron number in its outermost electron shell, Free Radicals produce tissue damage.
Osmotic Activity is a passive process in which water diffuses across a cell membrane in response to a concentration gradient.
Endogenous compounds and drugs that inhibit or block the activity of ANTIDUIRETIC HORMONE RECEPTORS.
Chelating Activity involves non-covalent, often coordinated, bonding between a metal and a biological molecule or complex where the biological molecule forms a ring around the metal.
An Unknown Cellular or Molecular Interaction consists of an activity or association of biologic molecules, complexes, or subcellular components that is currently undetermined.
A novel, orally active, small molecule with potential antineoplastic activity.CHIR-265 binds and inhibits Raf kinases, which may result in a reduction of tumor cell growth and proliferation, and tumor cell death. In addition, this agent inhibits vascular endothelial growth factor receptor type 2 (VEGFR-2), thereby disrupting tumor angiogenesis. Raf kinases are critical enzymes in the Ras/Raf/MEK/ERK signaling pathway and are frequently upregulated in neoplasms. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=484456&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=484456&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61311"" NCI Thesaurus)
A second-generation, orally bioavailable dual kinase inhibitor with potential antineoplastic activity. EGFR/HER2 inhibitor AV-412 binds to and inhibits the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2), which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumors. This agent may be active against EGFR/HER2-expressing tumor cells that are resistant to first-generation kinase inhibitors. EGFR and HER2 are receptor tyrosine kinases that play major roles in tumor cell proliferation and tumor vascularization.
A chromosomal abnormality consisting of the presence of a third copy of chromosome 21 in somatic cells.
The levorotatory isomer of lactic acid, the biologically active isoform in humans. Lactic acid or lactate is produced during fermentation from pyruvate by lactate dehydrogenase. This reaction, in addition to producing lactic acid, also produces nicotinamide adenine dinucleotide (NAD) that is then used in glycolysis to produce energy source adenosine triphosphate (ATP).
An inorganic or organic molecule which binds metal ions. Metal chelators are frequently polydentate, indicating that they form multiple bonds with the metal ion, resulting in more stable coordination complexes.
A broad-spectrum phenyl hydroxamic acid inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. Abexinostat inhibits several isoforms of HDAC, resulting in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling; the selective transcription of tumor suppressor genes; and the tumor suppressor protein-mediated inhibition of tumor cell division and induction of tumor cell apoptosis. In addition, this agent has been shown to inhibit homologous recombination (HR) activity by inhibiting the expression of RAD51. RAD51, a homologue of bacterial RecA, assists in the repair of DNA double-strand breaks (DSBs).
An electrocardiographic finding in leads V1 or V2 of an initial R wave duration greater than or equal to 40 ms, R wave greater than S wave, upright T wave, with accompanying ST elevation, which is suggestive of acute myocardial infarction of the posterior wall of the left ventricle. Evidence of inferior or lateral myocardial infarction is usually also present. (CDISC)
An electrocardiographic finding of ST and T wave abnormalities in the absence of pathologic Q waves, which is suggestive of myocardial infarction in one or more regions of the heart. (CDISC)
An electrocardiographic finding of a myocardial infarction that does not produce elevations in the ST segment of the EKG.
Any inhibitor of the proline-specific serine protease dipeptidyl peptidase 4 (DPP-4), with hypoglycemic activity. DPP-4 inhibitors bind to DPP-4 and inhibit the breakdown of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This prolongs incretin activity, increases postprandial insulin release, decreases glucagon release, delays gastric emptying and lowers blood glucose levels. The risk for hypoglycemia is negligible with the use of DPP-4 inhibitors.
Any agent that binds to and activates any of the opioid receptor subtypes. Opioid receptor agonists mimic the actions of endogenous opioid peptides.
Peptide hormones that cause an increase in the absorption of GLUCOSE by cells within organs such as LIVER, MUSCLE and ADIPOSE TISSUE. During normal metabolism insulins are produced by the PANCREATIC BETA CELLS in response to increased GLUCOSE. Natural and chemically-modified forms of insulin are also used in the treatment of GLUCOSE METABOLISM DISORDERS such as DIABETES MELLITUS.
A family of lipo-soluble steroids important to the absorption, metabolism, and function of calcium and phosphorus and the growth and development of bone and tooth enamel. Found naturally in animal tissues, cholecalciferol (vitamin D3) is formed in the skin when ultraviolet light activates cholesterol conversion into vitamin D3. Ultraviolet irradiation of ergosterol (plant vitamin D) forms ergocalciferol (vitamin D2). (NCI04)
A phosphorylated aminosulfhydryl compound with cytoprotective activity. Amifostine is dephosphorylated by alkaline phosphatase to an active free sulfhydryl (thiol) metabolite in the body. The thiol metabolite binds to and detoxifies cytotoxic platinum-containing metabolites of cisplatin and scavenges free radicals induced by cisplatin and ionizing radiation. The elevated activity of this agent in normal tissues results from both the relative abundance of alkaline phosphatase in normal tissues and the greater vascularity of normal tissues compared to tumor tissues.
A myocardial infarction that produces elevation in the ST segments of the ECG.
No change in chronic Graft versus Host Disease (cGVHD) progression during the preceding 3 months.
Remission with remaining lymphoid nodules reflecting residual disease.
Kaposi sarcoma (KS) is an invasive angioproliferative inflammatory condition that occurs commonly in men infected with human immunodeficiency virus (HIV; see 609423). In the early stages of KS, lesions appear reactive and are stimulated to grow by the actions of inflammatory cytokines and growth factors. In the late stages of KS, a malignant phenotype that appears to be monoclonal can develop. Infection with human herpesvirus-8 (HHV-8), also known as KS-associated herpesvirus (KSHV), is necessary but not sufficient for KS development. Coinfection with HIV markedly increases the likelihood of KS development, and additional environmental, hormonal, and genetic cofactors likely contribute to its pathogenesis (summary by Foster et al., 2000). Suthaus et al. (2012) noted that HHV-8 is the etiologic agent not only of KS, but also of primary effusion lymphoma and plasma cell-type multicentric Castleman disease (MCD).
Microspherophakia (MSP) is a rare disease characterized by smaller and more spherical lenses than normal bilaterally, an increased anteroposterior thickness of the lens, and highly myopic eyes. Lens dislocation or subluxation may occur, leading to defective accommodation (summary by Ben Yahia et al., 2009). Microspherophakia may occur in association with ectopia lentis and glaucoma, Marfan syndrome (MFS; 154700), and Weill-Marchesani syndrome (WMS; 277600).
The disappearance of all signs of cancer in response to treatment accompanied by incomplete bone marrow recovery, as evidenced by persistent anemia, thrombocytopenia or neutropenia.
Hereditary sensory and autonomic neuropathy type VI is a severe autosomal recessive disorder characterized by neonatal hypotonia, respiratory and feeding difficulties, lack of psychomotor development, and autonomic abnormalities including labile cardiovascular function, lack of corneal reflexes leading to corneal scarring, areflexia, and absent axonal flare response after intradermal histamine injection (summary by Edvardson et al., 2012). For a discussion of genetic heterogeneity of hereditary sensory and autonomic neuropathy, see HSAN1 (162400).
A severe and rare form of alpha thalassemia characterized by the absence of alpha globin chains. It results in hydrops fetalis, severe anemia, hepatosplenomegaly, heart defects, and genitourinary abnormalities. It leads to death in utero or shortly thereafter.
Neuronal ceroid lipofuscinosis-11 is an autosomal recessive neurologic disorder characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur (summary by Smith et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).
SPG53 is an autosomal recessive neurologic disorder characterized by onset in infancy of delayed motor development progressing to upper and lower limb spasticity with impaired walking. Affected individuals also show mild to moderate cognitive impairment (summary by Zivony-Elboum et al., 2012).
Spastic paraplegia-54 is a complicated form of spastic paraplegia, a neurodegenerative disorder affecting fibers of the corticospinal tract. Affected individuals have delayed psychomotor development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions. Brain magnetic resonance spectroscopy shows an abnormal lipid peak (summary by Schuurs-Hoeijmakers et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
SPG56 is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive lower-limb spasticity resulting in walking difficulties. Upper limbs are often also affected, and some patients may have a subclinical axonal neuropathy (summary by Tesson et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Failure of therapy to control chronic Graft versus Host Disease (cGVHD).
An invasive breast carcinoma which is negative for expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of disorders of keratinization characterized primarily by abnormal skin scaling over the whole body. These disorders are limited to skin, with approximately two-thirds of patients presenting severe symptoms. The main skin phenotypes are lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur (summary by Fischer, 2009). Neither histopathologic findings nor ultrastructural features clearly distinguish between NCIE and LI. In addition, mutations in several genes have been shown to cause both lamellar and nonbullous ichthyosiform erythrodermal phenotypes (Akiyama et al., 2003). At the First Ichthyosis Consensus Conference in Soreze in 2009, the term 'autosomal recessive congenital ichthyosis' (ARCI) was designated to encompass LI, NCIE, and harlequin ichthyosis (ARCI4B; 242500) (Oji et al., 2010). NCIE is characterized by prominent erythroderma and fine white, superficial, semiadherent scales. Most patients present with collodion membrane at birth and have palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. In half of the cases, a nail dystrophy including ridging, subungual hyperkeratosis, or hypoplasia has been described. Ectropion, eclabium, scalp involvement, and loss of eyebrows and lashes seem to be more frequent in NCIE than in lamellar ichthyosis (summary by Fischer et al., 2000). In LI, the scales are large, adherent, dark, and pigmented with no skin erythema. Overlapping phenotypes may depend on the age of the patient and the region of the body. The terminal differentiation of the epidermis is perturbed in both forms, leading to a reduced barrier function and defects of lipid composition in the stratum corneum (summary by Lefevre et al., 2006). In later life, the skin in ARCI may have scales that cover the entire body surface, including the flexural folds, and the scales are highly variable in size and color. Erythema may be very mild and almost invisible. Some affected persons exhibit scarring alopecia, and many have secondary anhidrosis (summary by Eckl et al., 2005). For a discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 (242300).
The disposition to develop an allergic reaction.
Familial myoclonus-1 is an autosomal dominant neurologic condition characterized by adult onset of cortical myoclonus manifest as involuntary jerks or movements affecting the face and limbs. Affected individuals can also experience falls without seizure activity or loss of consciousness (summary by Russell et al., 2012). Genetic Heterogeneity of Familial Myoclonus Also see MYOCL2 (618364), caused by mutation in the SCN8A gene (600702) on chromosome 12q13.
A dietary supplement containing the mineral calcium.
Charcot-Marie-Tooth disease type 4F is an autosomal recessive demyelinating neuropathy characterized by distal sensory impairment and distal muscle weakness and atrophy affecting the lower more than the upper limbs. Nerve conduction velocities are decreased and sural nerve biopsy shows loss of myelinated fibers. The age at onset is variable and can range from childhood to adult years. When the onset is in infancy, the phenotype is characterized as Dejerine-Sottas syndrome (DSS; 145900). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating Charcot-Marie-Tooth disease, see CMT4A (214400).
A deletion of 268 amino acids of the epidermal growth factor receptor protein from the valine at position 30 through the arginine at position 297 followed by the insertion of a glycine between the lysine at position 29 and the asparagine at position 298.
A worsening of chronic Graft versus Host Disease (cGVHD) manifestations during withdrawal of immunosuppressive therapy which does not exceed those at the beginning of the trial and improves after reinstatement of previous treatment.
An orally available nutritional supplement containing high amounts of the vitamin E family member tocotrienol with antioxidant, hypolipidemic and potential immunomodulating and antiproliferative activity. Upon oral administration, tocotrienol-rich fraction (TRF) accumulates in tumor cells and induces cell cycle arrest, programmed cell death, and inhibits tumor cell proliferation. In addition, this agent suppresses 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and inhibits angiogenesis. Rice bran oil, palm oil and annatto seed oil are common sources of TRF.
A qualification that describes the degree of certainty of the correctness of a microbial identification test result.
A congenital or acquired defect characterized by the presence of a hole in the retina.
A benign or malignant neoplasm which is not further characterized.
A constellation of neurobehavioral features observed following cessation or reduction of antenatal or postnatal drug exposure.
Objective evidence of disease perceptible to the examining practitioner (sign) and subjective evidence of disease perceived by the patient (symptom).
Mutations in the CRYGD gene have been found to cause multiple types of cataract, which have been described as aculeiform, crystalline aculeiform, crystalline, crystal, frosted, needle-shaped, fasciculiform, congenital cerulean, nonnuclear polymorphic congenital, central nuclear, lamellar, and punctate. Some patients also exhibit microcornea. Because multiple types of cataract are caused by mutation in the CRYGD gene, some of which display intrafamilial variability, several earlier distinct cataract entries in OMIM have been included here.
An X-linked dominant renal phosphate wasting disorder that results in rickets.
Any condition resulting in systemically elevated blood pressure that is attributed to an arterial source.
Among the Yakuts, an Asian population isolate that is located in the northeastern part of Siberia, Maksimova et al. (2010) ascertained a short stature syndrome involving autosomal recessive postnatal growth failure, small hands and feet, loss of visual acuity with abnormalities of color vision, abnormal nuclear shape in neutrophil granulocytes (Pelger-Huet anomaly; see 169400), and normal intelligence.
Pontine tegmental cap dysplasia (PTCD) refers to a neurologic condition characterized by a distinct pattern of hindbrain malformations apparent on brain imaging. The abnormalities affect the pons, medulla, and cerebellum. In neuroradiologic studies, the ventral side of the pons is flattened, whereas there is vaulting ('capping') of the dorsal pontine border into the fourth ventricle. Affected individuals show a variety of neurologic deficits, most commonly sensorineural deafness, impaired cranial nerve function, and variable psychomotor retardation (summary by Barth et al., 2007).
A radiopharmaceutical composed of the dichloride salt of the alpha-emitting isotope radium Ra 223, with antineoplastic activity. Like calcium, radium targets bone tissue and preferentially accumulates in osteoblastic lesions, such as those seen in areas of bone metastases. Radium Ra 223 forms complexes with hydroxyapatite and becomes incorporated into the bone matrix. The radioisotope Ra 223 kills bone cancer cells through local emission of high energy alpha particles, causing DNA double-strand breaks and tumor regression in the skeleton. The short range effects of alpha emission allows for localized DNA damage with limited toxicity to nearby healthy bone tissue.
The (1S,2R)-isomer of milnacipran that is used for the treatment of MAJOR DEPRESSIVE DISORDER.
Alkaloids from Rauwolfia serpentina Benth and other species. The prototype is RESERPINE, which is a depleter of catecholamines and serotonin from the sympathetic postganglionic fibers and brain areas. They have been used in hypertension and psychoses despite their wide range of potentially adverse effects.
X-linked spondyloepiphyseal dysplasia tarda is a condition that impairs bone growth and occurs almost exclusively in males. The name of the condition indicates that it affects the bones of the spine (spondylo-) and the ends of long bones (epiphyses) in the arms and legs. ""Tarda"" indicates that signs and symptoms of this condition are not present at birth, but appear later in childhood, typically between ages 6 and 10.Males with X-linked spondyloepiphyseal dysplasia tarda have skeletal abnormalities and short stature. Affected boys grow steadily until late childhood, when their growth slows. Their adult height ranges from 4 feet 6 inches (137 cm) to 5 feet 4 inches (163 cm). Impaired growth of the spinal bones (vertebrae) primarily causes the short stature. Spinal abnormalities include flattened vertebrae (platyspondyly) with hump-shaped bulges, progressive thinning of the discs between vertebrae, and an abnormal curvature of the spine (scoliosis or kyphosis). These spinal problems also cause back pain in people with this condition. Individuals with X-linked spondyloepiphyseal dysplasia tarda have a short torso and neck, and their arms are disproportionately long compared to their height.Other skeletal features of X-linked spondyloepiphyseal dysplasia tarda include an abnormality of the hip joint that causes the upper leg bones to turn inward (coxa vara); multiple abnormalities of the epiphyses, including a short upper end of the thigh bone (femoral neck); and a broad, barrel-shaped chest. A painful joint condition called osteoarthritis that typically occurs in older adults often develops in early adulthood in people with X-linked spondyloepiphyseal dysplasia tarda and worsens over time, most often affecting the hips, knees, and shoulders.
Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (de Lonlay et al., 2001; De Meirleir et al., 2003). Genetic Heterogeneity of Mitochondrial Complex III Deficiency Mitochondrial complex III deficiency can be caused by mutation in several different nuclear-encoded genes. See MC3DN2 (615157), caused by mutation in the TTC19 gene (613814) on chromosome 17p12; MC3DN3 (615158), caused by mutation in the UQCRB gene (191330) on chromosome 8q; MC3DN4 (615159), caused by mutation in the UQCRQ gene (612080) on chromosome 5q31; MC3DN5 (615160), caused by mutation in the UQCRC2 gene (191329) on chromosome 16p12; MC3DN6 (615453), caused by mutation in the CYC1 gene (123980) on chromosome 8q24; MC3DN7 (615824), caused by mutation in the UQCC2 gene (614461) on chromosome 6p21; MC3DN8 (615838), caused by mutation in the LYRM7 gene (615831) on chromosome 5q23; and MC3DN9 (616111), caused by mutation in the UQCC3 gene (616097) on chromosome 11q12. See also MTYCB (516020) for a discussion of a milder phenotype associated with isolated mitochondrial complex III deficiency and mutations in a mitochondrial-encoded gene.
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Hypohidrotic, or anhidrotic, ectodermal dysplasia (HED/EDA) is characterized by a triad of signs comprising sparse hair (hypotrichosis), abnormal or missing teeth (anodontia or hypodontia), and inability to sweat (anhidrosis or hypohidrosis). Typical clinical manifestations also include dryness of the skin, eyes, airways, and mucous membranes presumably due to the defective development of several exocrine glands. Hypohidrotic ectodermal dysplasia can be associated with dysmorphic features (forehead bumps, rings under the eyes, everted nose, and prominent lips) and occasionally with absent nipples (summary by Cluzeau et al., 2011).
Ectopia lentis is defined as an abnormal stretching of the zonular fibers that leads to lens dislocation, resulting in acute or chronic visual impairment (Greene et al., 2010). Citing the revised Ghent criteria for Marfan syndrome, Loeys et al. (2010) proposed the designation 'ectopia lentis syndrome' (ELS) for patients with ectopia lentis and a mutation in the FBN1 gene who lack aortic involvement, to highlight the systemic nature of the condition and to emphasize the need for assessment of features outside the ocular system (see DIAGNOSIS). Genetic Heterogeneity of Isolated Ectopia Lentis An autosomal recessive form of isolated ectopia lentis (ECTOL2; 225100) is caused by mutation in the ADAMTSL4 gene (610113).
An electrocardiographic finding suggestive of dextrocardia with situs inversus, characterized by reversal of normal anterior R wave progression and the appearance of reversal of the right and left arm electrodes. (CDISC)
The lead has been removed from the body.
An electrocardiographic finding showing a current of injury with ST elevation. No specification is provided for localization. (CDISC)
A drug hypersensitivity reaction with a relatively long latency period after exposure characterized by rash, fever, lymphadenopathy, hematologic abnormalities including eosinophilia and atypical lymphocytosis and internal organ involvement. Clinical presentation is highly variable. Eosinophilia is present in 50-90% of cases.
SOFT syndrome is characterized by severely short long bones, peculiar facies associated with paucity of hair, and nail anomalies. Growth retardation is evident on prenatal ultrasound as early as the second trimester of pregnancy, and affected individuals reach a final stature consistent with a height age of 6 years to 8 years. Relative macrocephaly is present during early childhood but head circumference is markedly low by adulthood. Psychomotor development is normal. Facial dysmorphism includes a long, triangular face with prominent nose and small ears, and affected individuals have an unusual high-pitched voice. Clinodactyly, brachydactyly, and hypoplastic distal phalanges and fingernails are present in association with postpubertal sparse and short hair. Typical skeletal findings include short and thick long bones with mild irregular metaphyseal changes, short femoral necks, and hypoplastic pelvis and sacrum. All long bones of the hand are short, with major delay of carpal ossification and cone-shaped epiphyses. Vertebral body ossification is also delayed (summary by Sarig et al., 2012).
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX2 gene have cells of complementation group 5 (CG5, equivalent to CG10 and CGF). For information on the history of PBD complementation groups, see 214100.
An electrocardiographic finding of pathologic Q waves in leads III, aVF and often II, which is suggestive of myocardial infarction of the inferior wall of the left ventricle. (CDISC)
The determination of whether the microbe or lesion is resistant to drugs normally used in treatment.
A biosimilar of filgrastim, a recombinant form of the endogenous cytokine human granulocyte colony-stimulating factor (G-CSF), with hematopoietic activity. Tbo-filgrastim specifically binds to and activates G-CSF receptors with the same biological activity and stability as the endogenous cytokine, thereby controlling the production, differentiation, and function of neutrophilic granulocyte progenitors. This may decrease the duration and prevent the incidence of chemotherapy-induced neutropenia (CIN).
An acute inflammatory process affecting the peripheral nervous system and nerve roots. It results in demyelination. It is often caused by an acute viral or bacterial infection.
SPG49 is an autosomal recessive complicated form of spastic paraplegia, a neurodegenerative disorder of the corticospinal tracts. It is characterized by delayed psychomotor development, mental retardation, and onset of spastic paraplegia in the first decade. Affected individuals also have dysmorphic features, thin corpus callosum on brain imaging, and episodes of central apnea, which may be fatal (summary by Oz-Levi et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
A lipid microsphere (LM)-based formulation containing the poorly water soluble taxane docetaxel, a semi-synthetic analogue of paclitaxel, with antineoplastic activity. Docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizing tubulin and inhibiting microtubule disassembly, which causes cell cycle arrest at the G2/M phase and leads to cell death. This agent also inhibits pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and induces various mediators of the inflammatory response. Compared to docetaxel alone, the LM formulation may enhance stability, improve efficacy and may reduce toxicity; this formulation does not contain toxic detergents needed to solubilize docetaxel which further improves its side effect profile.
Monoclonal antibodies that inhibit or prevent the proliferation of NEOPLASMS.
A benign epithelial neoplasm arising from primary epithelial germ cells of the piliary complex.
Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.
Syndrome is characterized by severe headaches, with or without other acute neurological symptoms, and diffuse segmental constriction of cerebral arteries that resolves spontaneously within 3 months.
The reemergence of intrahepatic cholangiocarcinoma after a period of remission.
Alternating hemiplegia of childhood is a rare syndrome of episodic hemi- or quadriplegia lasting minutes to days. Most cases are accompanied by dystonic posturing, choreoathetoid movements, nystagmus, other ocular motor abnormalities, autonomic disturbances, and progressive cognitive impairment (Mikati et al., 1992). The disorder may mimic or overlap with other disorders, including familial hemiplegic migraine (FHM1; 141500) and GLUT1 deficiency syndrome (606777) (Rotstein et al., 2009). Genetic Heterogeneity of Alternating Hemiplegia of Childhood See also AHC2 (614820), caused by mutation in the ATP1A3 gene (182350).
Since the initial discovery of the human electroencephalogram (EEG) by Berger (1929), it has been speculated that neural oscillations play a broad role in nervous systems and form the basis for higher cognitive functions and consciousness. The presence of a beta/gamma oscillation (18 to 50 Hz) is thought to represent an activated state of the underlying neuronal network. These beta (12-29 Hz) and gamma (30-50 Hz) brain rhythms involve gamma-aminobutyric acid type A (GABA-A) receptor action (Haenschel et al., 2000; summary by Porjesz et al., 2002).
Reduced anteroposterior thickness of the retina. This phenotype can be appreciated by retinal optical coherence tomography (OCT).
Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes, all of which resolve rapidly after delivery. However, the condition is associated with fetal complications, including placental insufficiency, premature labor, fetal distress, and intrauterine death. Some women with ICP may also be susceptible to oral contraceptive-induced cholestasis (OCIC) (summary by Pasmant et al., 2012). Genetic Heterogeneity of Intrahepatic Cholestasis of Pregnancy See also ICP3 (614972), caused by mutation in the ABCB4 gene (171060).
Metaphyseal dysplasia and maxillary hypoplasia with or without brachydactyly (MDMHB) is an autosomal dominant bone dysplasia characterized by metaphyseal flaring of long bones, enlargement of the medial halves of the clavicles, maxillary hypoplasia, variable brachydactyly, and dystrophic teeth (summary by Moffatt et al., 2013).
Repeated episodes of inflammation of a vein associated with venous thrombosis (blood clot formation within the vein).
The peroxisome biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 2 (CG2) have mutations in the PEX5 gene. For information on the history of PBD complementation groups, see 214100.
Primary shunt hyperbilirubinemia (PSHB) is a rare form of clinical jaundice characterized by increased serum levels of unconjugated bilirubin associated with ineffective erythropoiesis and a hyperplastic bone marrow. Peripheral red blood cell survival is normal (summary by Wang et al., 2006). Although primary shunt hyperbilirubinemia is clinically similar to Gilbert syndrome (143500), affected individuals do not have impaired activity of UDP-glucuronosyltransferase (UGT1A1; 191740). The term 'shunt' refers to a 'shortcut' in bilirubin production, from the bone marrow or from very young red blood cells as opposed to being derived from the hemoglobin of mature circulating erythrocytes (Israels et al., 1959).
A turning outward of the lip or lips, that is, eversion of the lips.
A morphological abnormality of a digit, i.e., of a finger or toe.
XLANP is an X-linked recessive hematologic disorder characterized by early-onset anemia and bone marrow erythroid hypoplasia with variable neutropenia. Some patients may have low platelets or platelet abnormalities. The severity is variable. Some patients have shown a favorable response to corticosteroid treatment (summary by Hollanda et al., 2006 and Sankaran et al., 2012). In some cases, the disorder may resemble Diamond-Blackfan anemia (see, e.g, DBA1; 105650) (Sankaran et al., 2012; Parrella et al., 2014; Klar et al., 2014).
X-linked autism-6 is a neurodevelopmental disorder that affects only males. Some patients may respond favorably to carnitine supplementation (summary by Ziats et al., 2015). Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). For a discussion of heterogeneity of autism, see 209850.
Early infantile epileptic encephalopathy-36 is an X-linked dominant neurodevelopmental disorder characterized by onset of seizures in infancy followed by delayed psychomotor development. Some patients may have dysmorphic features. Only females with this specific phenotype have been reported (summary by Dimassi et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see 308350. For a discussion of the classification of CDGs, see CDG1A (212065).
An X-linked recessive syndrome caused by loss-of-function mutation(s) in IGSF1, encoding immunoglobulin superfamily member 1. This condition can result in central hypothyroidism, macroorchidism, delayed puberty, and variable prolactin deficiency.
Beta-propeller protein-associated neurodegeneration (BPAN) is typically characterized by early-onset seizures, infantile-onset developmental delay, intellectual disability, absent to limited expressive language, motor dysfunction (ataxia), and abnormal behaviors often similar to autism spectrum disorder. Seizure types including generalized (absence, tonic, atonic, tonic-clonic and myoclonic), focal with impaired consciousness, and epileptic spasms, as well as epileptic syndromes (West syndrome and Lennox-Gastaut syndrome) can be seen. With age seizures tend to resolve or become less prominent, whereas cognitive decline and movement disorders (progressive parkinsonism and dystonia) emerge as characteristic findings.
Median longitudinal ear length less than two SD above the mean determined by the maximal distance from the superior aspect to the inferior aspect of the external ear.
Polycystic dysgenetic disease of the parotid gland (PDDP) is a rare benign condition of the parotid gland. The disorder presents often in childhood or young adulthood, but may occur later in life. It occurs most commonly in females. Features include fluctuating and nontender swelling of the parotid gland bilaterally, without defects in salivary function. Histology shows replacement of the lobular portion of the parotid gland by multiple epithelial-lined cysts arising from the intercalated ducts. The cysts often contain altered salivary secretions, including spheroliths or microliths; eosinophilic congophilic deposits have also been described. Chronic inflammation is not present. The condition is thought to result from a developmental defect of the intercalated duct system. Surgery may be indicated for diagnosis or for cosmetic reasons (summary by Smyth et al., 1993; Layfield and Gopez, 2002; Eley et al., 2011).
UV-sensitive syndrome-1 is an autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling, without an increased risk of skin tumors. Patient cells show impaired recovery of RNA synthesis (RRS) after UV irradiation due to defective preferential repair of DNA damage in actively transcribing genes, although unscheduled DNA repair is normal. The cellular findings are consistent with a defect in transcription-coupled nucleotide excision repair (TC-NER) of UV damage (summary by Horibata et al., 2004). Genetic Heterogeneity of UV-Sensitive Syndrome See also UVSS2 (614621), caused by mutation in the ERCC8 gene (609412) on chromosome 5q12, and UVSS3 (614640), caused by mutation in the UVSSA gene (614632) on chromosome 4p16.
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia-8 is an autosomal recessive disorder characterized by abnormal development of hair, teeth, and nails.
The presence of misshapen or partially destroyed nail plates, often with accumulation of soft, yellow keratin between the dystrophic nail plate and nail bed, resulting in elevation of the nail plate.
Cortisone reductase deficiency (CRD) results from a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11-beta-hydroxysteroid dehydrogenase (HSD11B1; 600713). The oxoreductase activity of 11-beta-HSD requires the NADPH-regenerating enzyme hexose-6-phosphate dehydrogenase (H6PD; 138090) within the endoplasmic reticulum. Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females presenting in midlife with hirsutism, oligomenorrhea, and infertility. Biochemically, CRD is diagnosed through the assessment of urinary cortisol and cortisone metabolites and consists of measuring the tetrahydrocortisol (THF) plus 5-alpha-THF/tetrahydrocortisone (THE) ratio, which in CRD patients is typically less than 0.1 (reference range, 0.7 to 1.2) (summary by Lavery et al., 2008). Genetic Heterogeneity of Cortisone Reductase Deficiency CORTRD2 (614662) is caused by mutation in the HSD11B1 gene (600713) on chromosome 1q32.
Meningiomas are, in general, slowly growing benign tumors derived from the arachnoidal cap cells of the leptomeninges, the soft coverings of the brain and spinal cord. Meningiomas are believed to be the most common primary tumors of the central nervous system in man. The vast majority of meningiomas are sporadic; familial occurrence of meningioma is rare (Zang, 2001). Familial or multiple meningiomas may also be seen in tumor predisposition syndromes. Some patients with schwannomatosis (162091), caused by mutation in the SMARCB1 gene, may develop meningiomas. One patient with malignant gliomas (GLM2; 613028) associated with a mutation in the PTEN gene (601728) developed a meningioma (Staal et al., 2002).
Underdevelopment of the semicircular canal.
Congenital myasthenic syndrome-12 is an autosomal recessive neuromuscular disorder characterized by onset of proximal muscle weakness in the first decade. EMG classically shows a decremental response to repeated nerve stimulation. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors (summary by Senderek et al., 2011). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462).
Displacement of the thumb from its normal position.
A deficiency or slowing down of growth pre- and postnatally.
A pseudoepiphysis (which is a secondary ossification center distinct from the normal epiphysis) of one or more phalanges of the thumb.
16p11.2 deletion syndrome is a disorder caused by a deletion of a small piece of chromosome 16. The deletion occurs near the middle of the chromosome at a location designated p11.2.People with 16p11.2 deletion syndrome usually have developmental delay and intellectual disability. Most also have at least some features of autism spectrum disorders. These disorders are characterized by impaired communication and socialization skills, as well as delayed development of speech and language. In 16p11.2 deletion syndrome, expressive language skills (vocabulary and the production of speech) are generally more severely affected than receptive language skills (the ability to understand speech). Some people with this disorder have recurrent seizures (epilepsy).Some affected individuals have minor physical abnormalities such as low-set ears or partially webbed toes (partial syndactyly). People with this disorder are also at increased risk of obesity compared with the general population. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 deletion syndrome. Signs and symptoms of the disorder vary even among affected members of the same family. Some people with the deletion have no identified physical, intellectual, or behavioral abnormalities.
Abnormally increased density of metaphyseal bone.
Lymphoproliferative syndrome-1 is an autosomal recessive primary immunodeficiency characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinemia. Autoimmune disorders, such as autoimmune hemolytic anemia or renal disease, may also occur. Patients show a high EBV viral load and decreased invariant natural killer T cells. It is unknown whether patients with ITK mutations are intrinsically susceptible to development of lymphoma or dysgammaglobulinemia in the absence of EBV infection (summary by Stepensky et al., 2011; Linka et al., 2012). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240).
EEG abnormalities (epileptiform discharges) evoked by flashing lights or black and white striped patterns.
Increase in amplitude of a long-loop response upon somatosensory evoked potential testing, representing an electrically evoked myoclonic response.
Jerk-locked averaging (JLA) is used to record the timing and distribution of brain activity preceding brisk involuntary movements such as those observed in patients with myoclonus. JLA is capable of revealing a premyoclonus spike in the absence of paroxysmal activity in the routine EEG.
Os odontoideum is classified into two anatomic types (orthotopic and dystopic). Os odontoideum is defined as an ossicle that consists of smooth and separate caudal portions of the odontoid process. With orthotopic os odontoideum, the ossicle moves with the anterior arch of the atlas, while the dystopic type consists of an ossicle near the basion, or one that is fused with the clivus
Increased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.
Emery-Dreifuss muscular dystrophy is a genetically heterogeneous muscular disease that presents with muscular dystrophy, joint contractures, and cardiomyopathy with conduction defects (summary by Liang et al., 2011). For a discussion of genetic heterogeneity of EDMD, see 310300.
Failure to develop of the pineal gland, defined clinically as the absence of the pineal gland with no indication of the pineal gland even having been present.
Nonmidline cleft palate on the left and right sides.
CDG2L is an autosomal recessive multisystem disorder apparent from birth or early infancy. It is characterized by poor growth, gastrointestinal and liver abnormalities, delayed psychomotor development, hypotonia, recurrent infections, hematologic abnormalities, increased bleeding tendency, and hyperhidrosis or hyperkeratosis. More variable features include nonspecific dysmorphic facial features and cardiac septal defects. The disorder often results in death in infancy or the first years of life (summary by Rymen et al., 2015). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066).
Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with ARID1A mutations have a wide spectrum of manifestations, from severe intellectual disability and serious internal complications that could result in early death to mild intellectual disability (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900). The chromosome 1p36.11 duplication syndrome, in which the ARID1A gene is duplicated, is characterized by impaired intellectual development, microcephaly, dysmorphic facial features, and hand and foot anomalies.
Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with SMARCB1 mutations may have more severe neurodevelopmental deficits including severe intellectual disability, brain structural abnormalities, and no expressive words, as well as scoliosis (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding difficulties, and hypoplastic or absent fifth fingernails and fifth distal phalanges. Other more variable features may also occur. Patients with SMARCA4 mutations may have less coarse craniofacial appearances and fewer behavioral abnormalities than Coffin-Siris patients with mutations in other genes (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Acrodysostosis-2 is a rare skeletal dysplasia characterized by brachydactyly, facial dysostosis, and spinal stenosis. Many patients have intellectual disability and some have hormone resistance (summary by Michot et al., 2012 and Lee et al., 2012). For a discussion of genetic heterogeneity of acrodysostosis, see ACRDYS1 (101800).
Diarrhea-6 is a relatively mild, early-onset chronic diarrhea that may be associated with increased susceptibility to inflammatory bowel disease, small bowel obstruction, and esophagitis (Fiskerstrand et al., 2012). For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
UV-sensitive syndrome-2 is an autosomal recessive disorder characterized by cutaneous photosensitivity and increased freckling, without an increased risk of skin tumors. Patient cells show impaired recovery of RNA synthesis (RRS) after UV irradiation due to defective preferential repair of DNA damage in actively transcribing genes, although unscheduled DNA repair is normal. The cellular findings are consistent with a defect in transcription-coupled nucleotide excision repair (TC-NER) of UV damage (summary by Nardo et al., 2009). See also Cockayne syndrome type A (CSA; 216400), an allelic disorder with a more severe phenotype including neurologic symptoms and skeletal abnormalities. For a general phenotypic description and a discussion of genetic heterogeneity of UVSS, see UVSS1 (600630).
Keratoconus is a noninflammatory progressive corneal thinning disorder resulting in mixed myopia and irregular astigmatism. Characteristic features include stromal thinning, Vogt striae, Fleisher ring, and scissoring of the retinoscopic reflex with a fully dilated pupil. Symptoms usually develop in the second decade and are likely to progress in the third decade, whereas progression slows after age 30 years. The progression of keratoconus may result in severe visual impairment and some affected individuals require cornea transplantation. The prevalence of keratoconus is about 1 in 2,000 in Caucasian populations, and is a leading cause for cornea transplantation in developed countries (summary by Tang et al., 2005). For a discussion of genetic heterogeneity of keratoconus, see KTCN1 (148300).
Keratoconus is a clinical term used to describe a condition in which the cornea assumes a conical shape as a result of noninflammatory thinning and protrusion. Keratoconus is detected clinically by slit-lamp evaluation, which demonstrates stromal corneal thinning. Other clinical signs may include Vogt striae, iron ring, scarring, retroillumination signs such as the 'Charleaux oil droplet reflex,' and/or scissoring on retinoscopy; in subtle cases, the diagnosis may be confirmed by videokeratography. The estimated prevalence of keratoconus ranges from 50 to 230 per 100,000 in the general population, and approximately 6% to 23.5% of reported cases demonstrate familial transmission. Age of onset is at puberty and the disorder is progressive until the third or fourth decade of life, when it usually arrests. It is a major cause of cornea transplantation in developed countries (summary by Li et al., 2006). For a discussion of genetic heterogeneity of keratoconus, see KTCN1 (148300).
Keratoconus is a noninflammatory disorder in which there is thinning and ectasia of the cornea. The estimated prevalence varies from 29 to 86 per 100,000, although the condition may be underreported. The onset of disease is typically after puberty, with subsequent progression at a variable rate over the following decades. Visual acuity is initially reduced by irregular corneal astigmatism but scarring can also develop (summary by Liskova et al., 2010). For a discussion of genetic heterogeneity of keratoconus, see KTCN1 (148300).
Keratoconus (KTCN) is a noninflammatory thinning and consequent bulging of the cornea that results in distortion of the corneal surface, altered refractive powers of the eye (both axial and refractive), and reduced visual acuity. In more advanced cases, corneal scarring further reduces visual acuity. Symptoms are highly variable and depend on the stage of the progression of the disorder. The trait has an incidence of approximately 1 in 2,000 individuals and is the most common indication for corneal transplantation in the United States (summary by Gajecka et al., 2009). For a discussion of genetic heterogeneity of keratoconus, see KTCN1 (148300).
UV-sensitive syndrome-3 is an autosomal recessive disorder characterized by cutaneous photosensitivity and slight dyspigmentation, without an increased risk of skin tumors. Patient cells show impaired recovery of RNA synthesis (RRS) after UV irradiation due to defective preferential repair of DNA damage in actively transcribing genes, although unscheduled DNA repair is normal. The cellular findings are consistent with a defect in transcription-coupled nucleotide excision repair (TC-NER) of UV damage (summary by Itoh et al., 1994 and Nakazawa et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of UVSS, see UVSS1 (600630).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Roscioli et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Limitation of the extension of the hip, i.e., decreased ability to straighten the hip joint and thereby increase the angle between torso and thigh; moving the thigh or top of the pelvis backward.
Stuttering is a disorder of the flow of speech characterized by involuntary repetitions or prolongations of sounds or syllables, and by interruptions of speech known as blocks (summary by Raza et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of stuttering, see STUT1 (184450).
Cortisone reductase deficiency (CRD) is a disorder in which there is a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11-beta-hydroxysteroid dehydrogenase, encoded by the HSD11B1 gene. Purified 11-beta-HSD acts readily as a dehydrogenase, inactivating cortisol to cortisone; however, in the presence of a high NADPH/NADP+ ratio, generated in vivo through the activity of microsomal hexose-6-phosphate dehydrogenase (H6PD; 138090), 11-beta-HSD switches to ketoreductase activity and generates active glucocorticoid. Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females presenting later with hirsutism, oligomenorrhea, and infertility. Biochemically, CRD is diagnosed through the assessment of urinary cortisol and cortisone metabolites and consists of measuring the ratio of tetrahydrocortisol (THF) plus 5-alpha-THF to tetrahydrocortisone (THE), which in CRD patients is typically less than 0.1 (reference range, 0.7 to 1.2) (summary by Lawson et al., 2011). For a discussion of genetic heterogeneity of cortisone reductase deficiency, see CORTRD1 (604931).
Auriculocondylar syndrome (ARCND), also known as 'question-mark ear syndrome' or 'dysgnathia complex,' is an autosomal dominant craniofacial malformation syndrome characterized by highly variable mandibular anomalies, including mild to severe micrognathia, often with temporomandibular joint ankylosis, cleft palate, and a distinctive ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark. Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia (summary by Rieder et al., 2012). For a discussion of genetic heterogeneity of auriculocondylar syndrome, see ARCND1 (602483).
Peripartum cardiomyopathy (PPCM) is characterized by systolic heart failure presenting in the last month of pregnancy or the first 5 months postpartum. PPCM affects 1 in 300 to 1 in 3,000 pregnancies, with geographic hot spots of high incidence, such as Nigeria and Haiti. Although approximately half of affected women recover cardiac function postpartum, many patients progress to chronic heart failure, cardiac transplantation, or death. Data have suggested that antiangiogenic prolactin (176760) fragments may have an important role in causing the disease in some patients. Risk factors for PPCM also include preeclampsia (see 189800) and multiple gestation, suggesting a potential mechanistic overlap with these processes (summary by Patten et al., 2012).
16p11.2 duplication is a chromosomal change in which a small amount of genetic material within chromosome 16 is abnormally copied (duplicated). The duplication occurs near the middle of the chromosome at a location designated p11.2. This duplication can have a variety of effects. Common characteristics that occur in people with a 16p11.2 duplication include a low weight; a small head size (microcephaly); and developmental delay, especially in speech and language. Affected individuals also have an increased risk of behavioral problems. However, some people with the duplication have no identified physical or behavioral abnormalities.Developmental delay and intellectual disability can occur in people with a 16p11.2 duplication. Approximately one-third of children with this condition have delays in developing physical skills such as sitting, crawling, or walking. The average IQ of affected individuals is about 26 points lower than that of their parents without the duplication. About 80 percent of people with a 16p11.2 duplication have problems related to speech or language. Both expressive language skills (vocabulary and the production of speech) and receptive language skills (the ability to understand speech) can be affected.One of the most common behavioral problems associated with this chromosomal change is attention deficit hyperactivity disorder. Autism spectrum disorder, which affect communication and social skills, is diagnosed in about one in five people with a 16p11.2 duplication. Affected individuals also have an increased risk of mental health problems, including schizophrenia, anxiety, and depression. Recurrent seizures are possible in this condition, although they do not occur in most affected individuals.Other abnormalities that can occur with a 16p11.2 duplication include malformations of the kidneys and urinary tract. However, there is no particular pattern of physical abnormalities that characterizes 16p11.2 duplications; signs and symptoms related to the chromosomal change vary even among affected members of the same family.
Women show menstrual cycle-dependent physiologic changes in relation to sex hormone levels. Because ovulation triggers a significant change in the hormonal milieu that is similar to local inflammation, a 0.5 to 1.0 degree Celsius increase in basal body temperature after ovulation is commonly associated with progesterone secretion and is believed to be triggered by the induction of several inflammatory cytokines. Rare menstrual cycle-dependent febrile episodes have been reported, some of which have shown a luteal-phase-dependent pattern (summary by Jiang et al., 2012).
Hypertrophic cardiomyopathy (CMH) is characterized by unexplained cardiac hypertrophy: thickening of the myocardial wall in the absence of any other identifiable cause for left ventricular hypertrophy such as systemic hypertension or valvular heart disease. Myocyte hypertrophy, disarray, and fibrosis are the histopathologic hallmarks of this disorder. Clinical features are diverse and include arrhythmias, sudden cardiac death, and heart failure. With an estimated prevalence of 1 in 500, CMH is the most common cardiovascular genetic disease and the most common cause of sudden death in competitive athletes in the United States (summary by Song et al., 2006). For a discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy, see CMH1 (192600).
EXOSC3-related pontocerebellar hypoplasia (PCH) is characterized by abnormalities in the posterior fossa and degeneration of the anterior horn cells. At birth, skeletal muscle weakness manifests as hypotonia (sometimes with congenital joint contractures) and poor feeding. In persons with prolonged survival, spasticity, dystonia, and seizures become evident. Within the first year of life respiratory insufficiency and swallowing difficulties are common. Intellectual disability is severe. Life expectancy ranges from a few weeks to adolescence. To date, 51 individuals with PCH from 36 families with mutation of EXOSC3 have been described.
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
Oral commissures positioned superior to the midline labial fissure.
Alar clefts most commonly occur in association with cleft lip and/or other craniofacial anomalies. The basic embryonic mechanism in alar clefts involves failure of fusion between the medial and the lateral nasal processes during the sixth to tenth weeks. The medial process gives rise to one-half of the nasal septum and the medial crus of the lower lateral alar cartilage, and the lateral process gives rise to the external wall of the nose, nasal bones, upper lateral cartilage, alae, and lateral crus of the lower lateral cartilage. The dorsum and apex of the nose, which are derived from the frontonasal process, are usually well preserved in patients with isolated alar cleft (summary by Richieri-Costa and Guion-Almeida, 2009).
Membranous nephropathy, a major cause of the nephrotic syndrome in adults, is characterized by the presence of glomerular deposits that typically contain immunoglobulin and complement components. Two major antigens, both of which are membrane glycoproteins, have been identified in human membranous nephropathy. Neutral endopeptidase (MME; 120520) is the alloantigen involved in membranous nephropathy in neonates whose mothers have a deficiency of this enzyme. The second is the M-type phospholipase A2 receptor (PLA2R1; 604939), the first antigen identified in adults with idiopathic membranous nephropathy, which is generally considered to be an autoimmune disease. In addition, autoantibodies against aldose reductase (AKR1B1; 103880), mitochondrial superoxide dismutase-2 (SOD2; 147460), and THSD7A (612249) have been found in serum and glomeruli from patients with idiopathic membranous nephropathy. Familial occurrence has been noted by Short et al. (1984) and Bockenhauer et al. (2008) (summary by Stanescu et al., 2011 and Tomas et al., 2014).
Common variable immunodeficiency-8 with autoimmunity is an autosomal recessive disorder of immune dysregulation. Affected individuals have early childhood onset of recurrent infections, particularly respiratory infections, and also develop variable autoimmune disorders, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease. The presentation and phenotype are highly variable, even within families (summary by Lopez-Herrera et al., 2012 and Alangari et al., 2012). Immunologic findings are also variable and may include decreased B cells, hypogammaglobulinemia, and deficiency of CD4+ T regulatory (Treg) cells (Charbonnier et al., 2015). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
COXPD10 is an autosomal recessive disorder resulting in variable defects of mitochondrial oxidative respiration. Affected individuals present in infancy with hypertrophic cardiomyopathy and lactic acidosis. The severity is variable, but can be fatal in the most severe cases (summary by Ghezzi et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Brown-Vialetto-Van Laere syndrome-2 is an autosomal recessive progressive neurologic disorder characterized by early childhood onset of sensorineural deafness, bulbar dysfunction, and severe diffuse muscle weakness and wasting of the upper and lower limbs and axial muscles, resulting in respiratory insufficiency. Some patients may lose independent ambulation. Because it results from a defect in riboflavin metabolism, some patients may benefit from high-dose riboflavin supplementation (summary by Johnson et al., 2012; Foley et al., 2014). For discussion of genetic heterogeneity of Brown-Vialetto-Van Laere syndrome, see BVVLS1 (211530).
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Mutations in the MVD gene have been found to cause multiple types of porokeratosis, which have been described as disseminated superficial actinic porokeratosis (DSAP), nonactinic disseminated superficial porokeratosis (DSP), solar facial porokeratosis, linear porokeratosis, and hyperkeratotic porokeratosis. The preferred title of this entry was formerly 'Porokeratosis 7, Disseminated Superficial Actinic Type; POROK7.' Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life (summary by Wu et al., 2004 and Zhang et al., 2012). For a discussion of genetic heterogeneity of porokeratosis, see 175800.
CDG2K is an autosomal recessive disorder with a variable phenotype. Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Serum transferrin analysis shows a CDG type II pattern (summary by Foulquier et al., 2012). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066).
Familial glucocorticoid deficiency is a rare autosomal recessive disorder characterized by an inability of the adrenal cortex to produce cortisol in response to stimulation by adrenocorticotropic hormone (ACTH). Affected individuals typically present within the first few months of life with symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, hypoglycemia, convulsions, and shock. The disease is life-threatening if untreated (summary by Meimaridou et al., 2012). For a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200).
MEGDEL (3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like) syndrome is characterized in neonates by hypoglycemia and a sepsis-like clinical picture for which no infectious agent can be found. During the first year of life feeding problems, failure to thrive, and/or truncal hypotonia become evident; many infants experience (transient) liver involvement ranging from undulating transaminases to prolonged hyperbilirubinemia and near-fatal liver failure. By age two years progressive deafness, dystonia, and spasticity prevent further psychomotor development and/or result in loss of acquired skills. Affected children are completely dependent on care for all activities of daily living; speech is absent.
Mitochondrial pyruvate carrier deficiency is an autosomal recessive metabolic disorder characterized by delayed psychomotor development and lactic acidosis with a normal lactate/pyruvate ratio resulting from impaired mitochondrial pyruvate oxidation (summary by Bricker et al., 2012).
Shortened telomeres can cause a wide variety of clinical features that constitute a phenotypic spectrum. The most severe form is dyskeratosis congenita (see, e.g., 127750), characterized by early childhood onset of skin abnormalities, bone marrow failure, predisposition to malignancy, and risk of pulmonary and hepatic fibrosis. Adult-onset pulmonary fibrosis is the most common manifestation of mutant telomerase genes. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Phenotype, age at onset, and severity are determined by telomere length, not just telomerase mutation (summary by Armanios, 2009). The genetic diagnosis of telomere-related bone marrow failure and pulmonary fibrosis has implications for treatment because affected individuals generally do not respond to immunosuppression and may be at increased risk for fatal complications after bone marrow or lung transplantation (Parry et al., 2011). Genetic Heterogeneity of Telomere-Related Pulmonary Fibrosis and/or Bone Marrow Failure Also see PFBMFT2 (614743), caused by mutation in the TERC gene (602322) on chromosome 3q26; PFBMFT3 (616373), caused by mutation in the RTEL1 gene (608833) on chromosome 20q13; and PFBMFT4 (616371), caused by mutation in the PARN gene (604212) on chromosome 16p13.
HCFP3 is an autosomal recessive congenital cranial dysinnervation disorder characterized by isolated dysfunction of the seventh cranial nerve resulting in facial palsy. Additional features may include orofacial anomalies, such as smooth philtrum, lagophthalmos, swallowing difficulties, and dysarthria, as well as hearing loss. There is some phenotypic overlap with Moebius syndrome (see, e.g., 157900), but patients with HCFP usually retain full eye motility or have esotropia without paralysis of the sixth cranial nerve (summary by Vogel et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of hereditary congenital facial paresis, see 601471.
Mutations in the integrin alpha-3 gene are associated with disrupted basement-membrane structures and compromised barrier functions in kidney, lung, and skin. Patients exhibit a multiorgan disorder that includes congenital interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa. The respiratory and renal features predominate, and lung involvement accounts for the lethal course of the disease (summary by Has et al., 2012).
Hyperphosphatasia with mental retardation syndrome-2 is an autosomal recessive disorder characterized by moderately to severely delayed psychomotor development, facial dysmorphism, brachytelephalangy, and increased serum alkaline phosphatase (hyperphosphatasia). Some patients may have additional features, such as cardiac septal defects or seizures (summary by Krawitz et al., 2012). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of hyperphosphatasia with mental retardation syndrome, see HPMRS1 (239300). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Distal hereditary motor neuronopathy type VB is an autosomal dominant neurologic disorder characterized by onset in the first or second decade of distal muscle weakness and atrophy, primarily affecting the intrinsic hand muscles, but also affecting the lower legs, resulting in abnormal gait and pes cavus (summary by Beetz et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN (dHMN), see HMN type I (HMN1; 182960).
A multiple congenital anomalies syndrome characterised by moderate postnatal overgrowth, macrocephaly, craniofacial dysmorphism (including high forehead and anterior hairline, downslanting palpebral fissures, prominent chin), developmental delay, and intellectual disability. Additional variable manifestations include unusual behaviour, with or without autistic traits, as well as ocular (e.g. strabismus, nystagmus, optic disc pallor/hypoplasia), gastrointestinal (e.g. vomiting, chronic diarrhoea, constipation), musculoskeletal (e.g. scoliosis and pectus excavatum), hand/foot (e.g. long, tapered fingers) and central nervous system (e.g. slightly enlarged ventricles) anomalies. The disease is caused by heterozygous mutation in the NFIX gene on chromosome 19p13.
Nonprogressive cerebellar ataxia with mental retardation is an autosomal dominant neurodevelopmental disorder characterized by mildly delayed psychomotor development, early onset of cerebellar ataxia, and intellectual disability later in childhood and adult life. Other features may include neonatal hypotonia, dysarthria, and dysmetria. Brain imaging in some patients shows cerebellar atrophy. Dysmorphic facial features are variable (summary by Thevenon et al., 2012).
C3 glomerulopathy is a group of related conditions that cause the kidneys to malfunction. The major features of C3 glomerulopathy include high levels of protein in the urine (proteinuria), blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in many areas of the body. Affected individuals may have particularly low levels of a protein called complement component 3 (or C3) in the blood.The kidney problems associated with C3 glomerulopathy tend to worsen over time. About half of affected individuals develop end-stage renal disease (ESRD) within 10 years after their diagnosis. ESRD is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.Researchers have identified two major forms of C3 glomerulopathy: dense deposit disease and C3 glomerulonephritis. Although the two disorders cause similar kidney problems, the features of dense deposit disease tend to appear earlier than those of C3 glomerulonephritis, usually in adolescence. However, the signs and symptoms of either disease may not begin until adulthood.One of the two forms of C3 glomerulopathy, dense deposit disease, can also be associated with other conditions unrelated to kidney function. For example, people with dense deposit disease may have acquired partial lipodystrophy, a condition characterized by a lack of fatty (adipose) tissue under the skin in the upper part of the body. Additionally, some people with dense deposit disease develop a buildup of yellowish deposits called drusen in the light-sensitive tissue at the back of the eye (the retina). These deposits usually appear in childhood or adolescence and can cause vision problems later in life.
Aplasia of a toe. That is, absence of all phalanges of a non-hallux digit of the foot and the associated soft tissues.
Karyomegalic tubulointerstitial nephritis (KTN) is a rare kidney disease characterized clinically by onset in the third decade of progressive renal failure. Renal biopsy shows chronic tubulointerstitial nephritis and interstitial fibrosis associated with enlarged and atypical tubular epithelial cell nuclei (summary by Baba et al., 2006).
Spermatogenic failure-10 is associated with a defective annulus, a ring structure that demarcates the midpiece and the principal piece of the sperm tail. The firm attachment of the annulus to the flagellar membrane suggests that it may supply mechanical support and prevent displacement of the caudal mitochondrial helix (summary by Kuo et al., 2012). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. The phenotype includes the alternative clinical designation Walker-Warburg syndrome (WWS). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Manzini et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Autosomal recessive spinocerebellar ataxia-13 is an autosomal recessive neurologic disorder characterized by delayed psychomotor development beginning in infancy. Affected individuals show mild to profound mental retardation with poor or absent speech as well as gait and stance ataxia and hyperreflexia. Most individuals also have eye movement abnormalities. Brain MRI shows cerebellar atrophy and ventriculomegaly (summary by Guergueltcheva et al., 2012).
Human herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi sarcoma, primary effusion lymphoma, and some forms of multicentric Castleman disease (Pedergnana et al., 2012). See 148000 for general phenotypic information on these diseases, as well as information on HHV-8-associated pathogenesis.
Primary microcephaly (MCPH) is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean and mental retardation, with no other associated malformations and with no apparent etiology. Most cases of primary microcephaly show an autosomal recessive mode of inheritance (Woods et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most cases of OI are autosomal dominant with mutations in 1 of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Martinez-Glez et al. (2012) described osteogenesis imperfecta type XIII, an autosomal recessive form of the disorder characterized by normal teeth, faint blue sclerae, severe growth deficiency, borderline osteoporosis, and an average of 10 to 15 fractures a year affecting both upper and lower limbs and with severe bone deformity.
Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous metabolic disorder of cobalamin (cbl; vitamin B12) metabolism, which is essential for hematologic and neurologic function. Biochemically, the defect causes decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective enzymes methylmalonyl-CoA mutase (MUT; 609058) and methyltetrahydrofolate:homocysteine methyltransferase, also known as methionine synthase (MTR; 156570). The cblJ type is phenotypically and biochemically similar to the cblF type (MAHCF; 277380) (summary by Coelho et al., 2012).
The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 3 (CG3) have mutations in the PEX12 gene. For information on the history of PBD complementation groups, see 214100.
This form of autosomal recessive nonsyndromic deafness is sensorineural and shows prelingual onset (Delmaghani et al., 2012).
The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 4 (CG4, equivalent to CG6 and CGC) have mutations in the PEX6 gene. For information on the history of PBD complementation groups, see 214100.
Peroxisome biogenesis disorder-4B (PBD4B) includes the overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders (PBDs). The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX6 gene have cells of complementation group 4 (CG4, equivalent to CG6 and CGC). For information on the history of PBD complementation groups, see 214100.
The peroxisomal biogenesis disorder (PBD) Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 5 (CG5, equivalent to CG10 and CGF) have mutations in the PEX2 gene. For information on the history of PBD complementation groups, see 214100.
STK4 deficiency results in a primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect (Abdollahpour et al., 2012; Nehme et al., 2012).
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 7 (CG7, equivalent to CGB) have mutations in the PEX10 gene. For information on the history of PBD complementation groups, see 214100.
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood. Some patients with PEX10 mutations have a milder disorder characterized by childhood-onset cerebellar ataxia and neuropathy without mental retardation (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX10 gene have cells of complementation group 7 (CG7, equivalent to CGB). For information on the history of PBD complementation groups, see 214100.
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX26 gene have cells of complementation group 8 (CG8, equivalent to CGA). For information on the history of PBD complementation groups, see 214100.
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 9 (CG9, equivalent to CGD) have mutations in the PEX16 gene. For information on the history of PBD complementation groups, see 214100.
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX16 gene have cells of complementation group 9 (CG9, equivalent to CGD). For information on the history of PBD complementation groups, see 214100.
Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) is an autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies (summary by Zhou et al., 2012).
DSMA5 is an autosomal recessive neurologic disorder characterized by young adult onset of slowly progressive distal muscle weakness and atrophy resulting in gait impairment and loss of reflexes due to impaired function of motor nerves. Sensation and cognition are not impaired (summary by Blumen et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of distal SMA, see HMN1 (182960).
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 12 (CG12, equivalent to CGG) have mutations in the PEX3 gene. For information on the history of PBD complementation groups, see 214100.
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 13 (CG13, equivalent to CGH) have mutations in the PEX13 gene. For information on the history of PBD complementation groups, see 214100.
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX13 gene have cells of complementation group 13 (CG13, equivalent to CGH). For information on the history of PBD complementation groups, see 214100.
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 14 (CG14, equivalent to CGJ) have mutations in the PEX19 gene. For information on the history of PBD complementation groups, see 214100.
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group K (CGK) have mutations in the PEX14 gene. For information on the history of PBD complementation groups, see 214100.
Patients with sinoatrial node dysfunction and deafness have congenital severe to profound deafness without vestibular dysfunction, associated with episodic syncope due to intermittent pronounced bradycardia (Baig et al., 2011). See Jervell and Lange-Nielsen syndrome (220400) for discussion of another deafness syndrome with impaired cardiac conduction.
PBD14B is an autosomal recessive peroxisome biogenesis disorder characterized clinically by mild intellectual disability, congenital cataracts, progressive hearing loss, and polyneuropathy (Ebberink et al., 2012), all of which had been observed in patients with mild peroxisomal biogenesis disorders (e.g., Kelley et al., 1986; Poll-The et al., 1987). Additionally, recurrent migraine-like episodes following mental stress or physical exertion, not a common feature in peroxisome disorders, was reported. Thoms and Gartner (2012) classified the disorder described by Ebberink et al. (2012) in their patient as a mild 'Zellweger syndrome (214100) spectrum' (ZSS) disorder. See PBD1B (601539) for a phenotypic description and discussion of genetic heterogeneity of less severe phenotypes on the Zellweger syndrome spectrum. See PBD9B (614879) for another atypical peroxisome biogenesis disorder.
COXPD11 is a severe multisystemic autosomal recessive disorder characterized by neonatal hypotonia and lactic acidosis. Affected individuals may have respiratory insufficiency, foot deformities, or seizures, and all reported patients have died in infancy. Biochemical studies show deficiencies of multiple mitochondrial respiratory enzymes (summary by Garcia-Diaz et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
COXPD12 is an autosomal recessive mitochondrial neurologic disorder characterized by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression, associated with T2-weighted hyperintensities in the deep cerebral white matter, brainstem, and cerebellar white matter. Serum lactate is increased due to a defect in mitochondrial respiration. There are 2 main phenotypic groups: those with a milder disease course and some recovery of skills after age 2 years, and those with a severe disease course resulting in marked disability (summary by Steenweg et al., 2012). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. Ovarian dysfunction ranges from gonadal dysgenesis (absent or streak gonads) manifesting as primary amenorrhea to primary ovarian insufficiency (POI) defined as cessation of menses before age 40 years. Fertility in affected males is reported as normal (although the number of reported males is limited). Neurologic features described in some individuals with Perrault syndrome include learning difficulties and developmental delay, cerebellar ataxia, and motor and sensory peripheral neuropathy.
Toenail that appears thin when viewed on end.
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia of the hair/nail type is a rare congenital condition characterized by hypotrichosis and nail dystrophy without nonectodermal or other ectodermal manifestations. Hypotrichosis usually occurs after birth with varying degrees of severity, ranging from mild hair loss to complete atrichia, including the loss of scalp hair, beard, eyebrows, eyelashes, axillary hair, and pubic hair. Nail dystrophy affects all 20 digits by causing short fragile nails or spoon nails (koilonychia) (summary by Lin et al., 2012).
Combined oxidative phosphorylation deficiency-13 is an autosomal recessive multisystem disorder resulting from mitochondrial dysfunction. Affected individuals develop severe neurologic impairment in the first months of life, including hypotonia, abnormal dystonic movements, hearing loss, poor feeding, global developmental delay, and abnormal eye movements. Brain imaging shows signal abnormalities in putamen, basal ganglia, caudate nuclei, or corpus callosum, as well as delayed myelination. Analysis of patient tissues shows multiple defects in enzymatic activities of the mitochondrial respiratory chain, although some tissues may show normal values since tissue expression of the mitochondrial defect and metabolic needs of specific tissues are variable (summary by Vedrenne et al., 2012).
The spectrum of FARS2 deficiency ranges from the infantile-onset phenotype, characterized by epileptic encephalopathy with lactic acidosis and poor prognosis (70% of affected individuals), to the later-onset phenotype, characterized by spastic paraplegia, less severe neurologic manifestations, and longer survival (30% of affected individuals). To date FARS2 deficiency has been reported in 37 individuals from 25 families. Infantile-onset phenotype. Seizures are difficult to control and may progress quickly at an early age to intractable seizures with frequent status epilepticus; some children have hypsarrhythmia on EEG. All have developmental delay; most are nonverbal and unable to walk. Feeding difficulties are common. More than half of affected children die in early childhood. Later-onset phenotype. All affected individuals have spastic paraplegia manifested by weakness, spasticity, and exaggerated reflexes of the lower extremities associated with walking difficulties; some have developmental delay/intellectual disability; some have brief seizures that resolve over time.
Multiple types of congenital heart defects-3 (CHTD3) is an autosomal dominant condition characterized by various types of congenital heart defects and low atrial rhythm (van de Meerakker et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of multiple types of congenital heart defects, see 306955.
KCNT1-related epilepsy is most often associated with two phenotypes: epilepsy of infancy with migrating focal seizures (EIMFS) and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). EIMFS is characterized by seizures, typically focal and asynchronous, beginning in the first six months of life with associated developmental plateau or regression. Autonomic manifestations (e.g., perioral cyanosis, flushing, apnea) are common. Seizures are intractable to multiple anticonvulsants and progress to become nearly continuous by age six to nine months. ADNFLE is characterized by clusters of nocturnal motor seizures that vary from simple arousals to hyperkinetic events with tonic or dystonic features. Individuals with KCNT1-related ADNFLE are more likely to develop seizures at a younger age, have cognitive comorbidity, and display psychiatric and behavioral problems than individuals with ADNFLE due to other causes. Less common seizure phenotypes in individuals with KCNT1-related epilepsy include West syndrome, Ohtahara syndrome, early myoclonic encephalopathy, leukodystrophy and/or leukoencephalopathy, focal epilepsy, and multifocal epilepsy. Additional neurologic features include hypotonia, microcephaly developing by age 12 months, strabismus, profound developmental delay, and additional movement disorders. Other systemic manifestations including pulmonary hemorrhage caused by prominent systemic-to-pulmonary collateral arteries or cardiac arrhythmia have been reported.
Pontocerebellar hypoplasia type 8 is an autosomal recessive neurodevelopmental disorder characterized by severe psychomotor retardation, abnormal movements, hypotonia, spasticity, and variable visual defects. Brain MRI shows pontocerebellar hypoplasia, decreased cerebral white matter, and a thin corpus callosum (summary by Mochida et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
Leptin deficiency is characterized by severe early-onset obesity, hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic dysfunction (Ozata et al., 1999).
Leptin receptor deficiency is characterized by severe early-onset obesity, major hyperphagia, hypogonadotropic hypogonadism, and neuroendocrine/metabolic dysfunction (summary by Dehghani et al., 2018).
Pontocerebellar hypoplasia type 7 is a severe neurologic condition characterized by delayed psychomotor development, hypotonia, breathing abnormalities, and gonadal abnormalities (summary by Anderson et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
Intrahepatic cholestasis of pregnancy is a reversible form of cholestasis that occurs most often in the third trimester of pregnancy and recurs in 45 to 70% of subsequent pregnancies. Symptoms include pruritus, jaundice, increased serum bile salts, and abnormal liver enzymes, all of which resolve rapidly after delivery. However, the condition is associated with fetal complications, including placental insufficiency, premature labor, fetal distress, and intrauterine death. Women with ICP are also susceptible to oral contraceptive-induced cholestasis (OCIC). Ursodeoxycholic acid (UDCA) is an effective treatment for conditions caused by ABCB4 mutations (summary by Pasmant et al., 2012). Mutation in the ABCB4 gene accounts for about 15% of ICP cases (summary by Ziol et al., 2008). For a discussion of genetic heterogeneity of ICP, see ICP1 (147480).
The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFFD2 is an autosomal dominant disorder characterized by bitemporal skin lesions with variable facial findings, including thin and puckered periorbital skin, distichiasis and/or absent eyelashes, upslanting palpebral fissures, a flat nasal bridge with a broad nasal tip, large lips, and redundant facial skin. FFDD3 (227260) is characterized by the same facial features as FFDD2, but the inheritance is autosomal recessive (summary by Slavotinek et al., 2013). For a classification and a discussion of genetic heterogeneity of FFDD, see FFDD1 (136500).
The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFDD4 is characterized by isolated, preauricular skin lesions (summary by Slavotinek et al., 2013). For a classification and a discussion of genetic heterogeneity of FFDD, see FFDD1 (136500).
Carpenter syndrome-2 is an autosomal recessive multiple congenital malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet, in association with abnormal left-right patterning and other features, most commonly obesity, umbilical hernia, cryptorchidism, and congenital heart disease (summary by Twigg et al., 2012). For a discussion of genetic heterogeneity of Carpenter syndrome, see 201000.
Tantravahi et al. (2012) reported an apparently new syndrome involving massive splenomegaly, cytopenia, anhidrosis, chronic optic nerve edema, and vision loss.
Schuurs-Hoeijmakers syndrome is an autosomal dominant disorder characterized by mental retardation, distinct craniofacial features, and variable additional congenital abnormalities (summary by Schuurs-Hoeijmakers et al., 2016).
Phosphohydroxylysinuria is characterized by elevated phosphohydroxylysine in the urine. There is no clinical phenotype associated with this finding other than the urinary metabolites. This was confirmed by population genetic studies performed by Veiga-da-Cunha et al. (2013) (Hamosh, 2013).
Dystonia-24 is an autosomal dominant form of focal dystonia affecting the neck, laryngeal muscles, and muscles of the upper limbs (summary by Charlesworth et al., 2012).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. The brain shows cobblestone lissencephaly, a cortical malformation. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Vuillaumier-Barrot et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
CHCHD10-related disorders are characterized by a spectrum of adult-onset neurologic findings that can include: Mitochondrial myopathy (may also be early-onset): weakness, amyotrophy, exercise intolerance. Amyotrophic lateral sclerosis (ALS): progressive degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). Frontotemporal dementia (FTD): slowly progressive behavioral changes, language disturbances, cognitive decline, extrapyramidal signs. Late-onset spinal motor neuronopathy (SMAJ): weakness, cramps, and/or fasciculations; areflexia. Cerebellar ataxia: gait ataxia, kinetic ataxia (progressive loss of coordination of lower- and upper-limb movements), dysarthria/dysphagia, nystagmus, cerebellar oculomotor disorder. Because of the recent discovery of CHCHD10-related disorders and the limited number of affected individuals reported to date, the natural history of these disorders (except for SMAJ caused by the p.Gly66Val pathogenic variant) is largely unknown.
This autosomal recessive form of distal arthrogryposis, designated DA5D by McMillin et al. (2013), is characterized by severe camptodactyly of the hands, including adducted thumbs and wrists; mild camptodactyly of the toes; clubfoot and/or a calcaneovalgus deformity; extension contractures of the knee; unilateral ptosis or ptosis that is more severe on one side; a round-shaped face; arched eyebrows; a bulbous, upturned nose; and micrognathia. Notably, these patients do not have ophthalmoplegia. For a general phenotypic description and discussion of genetic heterogeneity of distal arthrogryposis, see DA1A (108120). For discussion of genetic heterogeneity of distal arthrogryposis type 5, see DA5 (108145).
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most cases of OI are autosomal dominant with mutations in 1 of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Shaheen et al. (2012) described osteogenesis imperfecta type XIV (OI14), an autosomal recessive form of the disorder characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years.
DYT-GNAL caused by a heterozygous GNAL pathogenic variant has been reported in more than 60 individuals to date. It is characterized by adult-onset isolated dystonia (i.e., no neurologic abnormalities other than tremor are evident on neurologic examination). The dystonia is most commonly focal and segmental, and rarely generalized. Dystonia is typically cervical in onset and commonly progresses to the cranial region (oromandibular/jaw, larynx, eyelids) and/or to one arm. Tremor reported in DYT-GNAL may be dystonic (i.e., occurring in a body part that shows at least minimal signs of dystonia) and may precede or follow the onset of dystonia. Intra- and interfamilial variability is considerable. DYT-GNAL caused by biallelic GNAL pathogenic variants, reported to date in two sibs from a consanguineous family, is characterized by mild intellectual disability and childhood-onset hypertonia that progresses to generalized dystonia.
Autosomal dominant mental retardation-18 is characterized by severe intellectual disability, limited language development, motor delay, and dysmorphic features, including hypertelorism and narrow palpebral fissures (summary by Luo et al., 2017).
Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) is characterized by global developmental delay, impaired intellectual development, axial hypotonia, and dysmorphic craniofacial features with microcephaly. Many patients have visual abnormalities, ranging from strabismus to optic nerve atrophy and retinal abnormalities. Affected individuals also develop spasticity, particularly of the lower limbs, and may have behavioral abnormalities (summary by Kuechler et al., 2015 and Kharbanda et al., 2017).
Cis-3-hexen-1-ol (C3HEX) is present in a wide range of foods and beverages, including wine and spirits, olive oil, vegetables, fruit, and green tea. C3HEX is commonly associated with sensory characteristics such as 'green' and 'grassy.' The probability of an individual's ability to detect C3HEX at a particular intensity (the R-index) can be estimated, and the threshold for detection is normally distributed (summary by Jaeger et al., 2010).
Colorectal cancer-12 is an autosomal dominant disorder characterized by a high-penetrance predisposition to the development of colorectal adenomas and carcinomas, with a variable tendency to develop multiple and large tumors. Onset usually occurs before age 40 years. The histologic features of the tumors may be unremarkable (Palles et al., 2013) or show microsatellite instability (MSI) (Elsayed et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of colorectal cancer, see 114500.
Mitochondrial DNA depletion syndrome-11 is an autosomal recessive mitochondrial disorder characterized by onset in childhood or adulthood of progressive external ophthalmoplegia (PEO), muscle weakness and atrophy, exercise intolerance, and respiratory insufficiency due to muscle weakness. More variable features include spinal deformity, emaciation, and cardiac abnormalities. Skeletal muscle biopsies show deletion and depletion of mitochondrial DNA (mtDNA) with variable defects in respiratory chain enzyme activities (summary by Kornblum et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041).
Primary microcephaly-10 (MCPH10) is an autosomal recessive disorder characterized by extremely small head size (-9 SD) at birth and death usually by 1 year of age. Neuropathologic examination shows severe loss of neurons as well as neuronal loss of polarity and abnormal dendritic maturation (summary by Yang et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Cytochrome c oxidase deficiency is a genetic condition that can affect several parts of the body, including the muscles used for movement (skeletal muscles), the heart, the brain, or the liver. Signs and symptoms of cytochrome c oxidase deficiency usually begin before age 2 but can appear later in mildly affected individuals.The severity of cytochrome c oxidase deficiency varies widely among affected individuals, even among those in the same family. People who are mildly affected tend to have muscle weakness (myopathy) and poor muscle tone (hypotonia) with no other related health problems. More severely affected people have problems in multiple body systems, often including severe brain dysfunction (encephalomyopathy). Approximately one-quarter of individuals with cytochrome c oxidase deficiency have a type of heart disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). Another possible feature of this condition is an enlarged liver (hepatomegaly), which may lead to liver failure. Most individuals with cytochrome c oxidase deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can cause nausea and an irregular heart rate, and can be life-threatening.Many people with cytochrome c oxidase deficiency have a specific group of features known as Leigh syndrome. The signs and symptoms of Leigh syndrome include loss of mental function, movement problems, hypertrophic cardiomyopathy, eating difficulties, and brain abnormalities. Cytochrome c oxidase deficiency is one of the many causes of Leigh syndrome.Many individuals with cytochrome c oxidase deficiency do not survive past childhood, although some individuals with mild signs and symptoms live into adolescence or adulthood.
Lymphoproliferative syndrome-2, also known as CD27 deficiency, is an autosomal recessive immunodeficiency disorder associated with persistent symptomatic EBV viremia, hypogammaglobulinemia, and impairment in specific antibody function resulting from impaired T cell-dependent B-cell responses and T-cell dysfunction (summary by van Montfrans et al., 2012). The phenotype can vary significantly, from asymptomatic borderline-low hypogammaglobulinemia, to a full-blown symptomatic systemic inflammatory response with life-threatening EBV-related complications, including hemophagocytic lymphohistiocytosis, a lymphoproliferative disorder, and malignant lymphoma requiring stem cell transplantation (summary by Salzer et al., 2013). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240).
Onset of disease at the age of between 16 and 40 years.
The mild variant of MSUD is characterized by increased plasma levels of branched-chain amino acids (BCAA) apparent at birth. Treatment with a low-protein diet free of BCAA can result in normal psychomotor development and lack of metabolic episodes; however, plasma levels of BCAA may remain elevated (summary by Oyarzabal et al., 2013). For a general description and a discussion of genetic heterogeneity of maple syrup urine disease, see 248600.
FILS syndrome is characterized by mild facial dysmorphism, mainly malar hypoplasia, livedo on the skin since birth, immunodeficiency resulting in recurrent infections, and short stature (summary by Pachlopnik Schmid et al., 2012).
Telangiectases (small dilated blood vessels) located near the surface of the skin of the cheeks.
Steel syndrome is characterized by characteristic facies, dislocated hips and radial heads, carpal coalition (fusion of carpal bones), short stature, scoliosis, and cervical spine anomalies. The dislocated hips are resistant to surgical intervention (summary by Flynn et al., 2010).
PEOA6 is characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA (mtDNA) deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression (summary by Ronchi et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640).
Mitochondrial complex III deficiency nuclear type 2 is an autosomal recessive severe neurodegenerative disorder that usually presents in childhood, but may show later onset, even in adulthood. Affected individuals have motor disability, with ataxia, apraxia, dystonia, and dysarthria, associated with necrotic lesions throughout the brain. Most patients also have cognitive impairment and axonal neuropathy and become severely disabled later in life (summary by Ghezzi et al., 2011). The disorder may present clinically as spinocerebellar ataxia or Leigh syndrome, or with psychiatric disturbances (Morino et al., 2014; Atwal, 2014; Nogueira et al., 2013). For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000).
Mitochondrial complex III deficiency is a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and the muscles used for movement (skeletal muscles). Signs and symptoms of mitochondrial complex III deficiency usually begin in infancy but can appear later.The severity of mitochondrial complex III deficiency varies widely among affected individuals. People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). More severely affected individuals have problems with multiple body systems, such as liver disease that can lead to liver failure, kidney abnormalities (tubulopathy), and brain dysfunction (encephalopathy). Encephalopathy can cause delayed development of mental and motor skills (psychomotor delay), movement problems, weak muscle tone (hypotonia), and difficulty with communication. Some affected individuals have a form of heart disease called cardiomyopathy, which can lead to heart failure. Most people with mitochondrial complex III deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis). Some affected individuals also have buildup of molecules called ketones (ketoacidosis) or high blood sugar levels (hyperglycemia). Abnormally high levels of these chemicals in the body can be life-threatening.Mitochondrial complex III deficiency can be fatal in childhood, although individuals with mild signs and symptoms can survive into adolescence or adulthood.
Proximal interphalangeal (PIP) flexion deformity of the little finger. That is, the PIP joint of a little finger is bent (flexed) and cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement.
Displacement of the 3rd finger towards the ulnar side (i.e., towards the ring finger).
In the resting position, the tip of the thumb is on, or near, the palm, close to the base of the fourth or fifth finger.
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies. It is usually associated with delayed psychomotor development and shortened life expectancy. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Stevens et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
A response indicating that a patient has or had severe cognitive impairments.
CMTDIF is an autosomal dominant neurologic disorder characterized by onset around adolescence of slowly progressive distal muscle atrophy and weakness affecting the upper and lower limbs and resulting in steppage gait. There is distal sensory impairment with decreased reflexes. Nerve conduction velocities are variable, ranging from the demyelinating to the axonal range (summary by Soong et al., 2013). For a discussion of genetic heterogeneity of CMTDI, see 606482.
Lissencephaly-5 is an autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development (summary by Radmanesh et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Platelet-type bleeding disorder-15 is an autosomal dominant form of macrothrombocytopenia. Affected individuals usually have no or only mild bleeding tendency, such as epistaxis. Laboratory studies show decreased numbers of large platelets and anisocytosis, but the platelets show no in vitro functional abnormalities (summary by Kunishima et al., 2013).
Restless legs syndrome (RLS) is a neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation (Bonati et al., 2003). For additional information and a discussion of heterogeneity of restless legs syndrome, see RLS1 (102300).
Osteosclerotic metaphyseal dysplasia is a rare condition characterized by developmental delay, hypotonia, and distinctive radiographic changes, including osteosclerosis localized predominantly to the metaphyses of the long bones. The shafts of the long bones are osteopenic. The skull appears to be spared. Seizures and later-onset spastic paraplegia have been reported. Laboratory abnormalities include elevated alkaline phosphatase levels in some, but not all, patients. Elevated urinary pyridinoline and deoxypyridinoline levels, markers of osteoclastic activity, have also been reported (summary by Nishimura and Kozlowski, 1993 and Kasapkara et al., 2013).
An increase in bone density within the clavicle.
Immunodeficiency-11A is an autosomal recessive primary immunodeficiency characterized by normal numbers of T and B lymphocytes, but defective intracellular signaling. There is a block in B-cell differentiation with increased numbers of transitional B cells and hypogammaglobulinemia, as well as decreased numbers of regulatory T cells and defects in T-cell function (summary by Greil et al., 2013 and Stepensky et al., 2013).
Immunodeficiency-56 is an autosomal recessive primary immunodeficiency characterized by B- and T-cell defects and variable dysfunction of NK cells. Patients tend to have normal numbers of lymphocytes, but show defective class-switched B cells, low IgG, defective antibody response, and defective T-cell responses to certain antigens (summary by Kotlarz et al., 2013).
AOA3 is an autosomal recessive progressive neurologic disorder with onset in the second decade of life (Al Tassan et al., 2012). For a discussion of genetic heterogeneity of ataxia-oculomotor apraxia, see AOA1 (208920).
Congenital hydrocephalus-2 is a congenital disorder with onset in utero. Affected individuals have hydrocephalus with variably dilated ventricles and variable neurologic sequelae. Some individuals have other brain abnormalities, including lissencephaly, thinning of the corpus callosum, and neuronal heterotopia. Most patients have delayed motor development and some have delayed intellectual development and/or seizures. Additional congenital features, including cardiac septal defects, iris coloboma, and nonspecific dysmorphic features, may be observed. Some patients die in utero, in infancy, or in early childhood, whereas others have long-term survival (summary by Shaheen et al., 2017). For a discussion of genetic heterogeneity of congenital hydrocephalus, see 233600.
An abnormality of the optic nerve in which the optic nerve is large and funneled and displays a conical excavation of the optic disc. The optic disc appears dysplastic.
A complete duplication affecting one or more of the phalanges of the thumb. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accesory bone appearing in the proximo-distal axis on x-rays, this is actually a different entity called a Pseudoepiphyses (see according terms) sometimes also refered to as Hyperphalangism.
A rare multiple congenital anomalies syndrome with characteristics of distinctive facial appearance (low frontal hairline, bilateral ptosis, prominent eyes, flat midface, broad, ?at nares, Cupid's bow upper lip vermilion and small, low-set, posteriorly rotated ears), cleft palate, conductive hearing loss, heart defects (atrial or ventricular septal defect) and mild developmental delay/intellectual disability.
An oxidized form of alpha-tocopherol with potent anticoagulant activity. Although the mechanism of action has not been fully elucidated, dietary supplementation with tocopherylquinone may lead to the inhibition of the vitamin K-dependent gamma-carboxylase (gamma-glutamyl carboxylase). This prevents the carboxylation of glutamyl residues in coagulation factor proteins and inhibits platelet aggregation and clotting.
A cancer vaccine comprised of nine class I major histocompatibility complex (MHC)-restricted breast cancer associated peptides, the tetanus toxoid helper peptide and the Toll-like receptor 3 (TLR3) agonist poly ICLC, with potential immunostimulatory and antineoplastic activities. The nine peptides derived from six cancer associated proteins are epidermal growth factor receptor 2 (HER2/neu), carcinoembryonic antigen (CEA) and four cancer/testis antigens (CTAs: MAGE-A1, -A3, -A10, and NY-ESO-1). Vaccination with this vaccine may elicit a specific cytotoxic T-lymphocyte (CTL) response against cells overexpressing these tumor associated antigens (TAAs). As a nonspecific T-helper epitope, tetanus toxoid helper peptide binds to class II MHC and results in long-term immunopotentiation by increasing the helper T-cell response. Poly ICLC, the double-stranded RNA molecules of polyinosinic-polycytidylic acid stabilized with poly L-lysine in carboxymethylcellulose, binds to TLR3 and induces the release of cytokines which may help boost the immune response against the TAAs.
A topical gel composed of a human papillomavirus (HPV) E1/E2 protein:protein interaction (PPI) inhibitor with potential antiviral activity. Upon topical application of AP611074, this agent prevents binding of the HPV viral proteins E1 to E2, thereby preventing viral DNA replication and growth of HPV. This inhibits viral proliferation and may prevent the formation of anogenital warts caused by HPV. The HPV proteins E1 and E2 are essential for HPV viral replication.
An immunoconjugate that consists of a humanized IgG1 antibody K7153A against the cell-surface antigen CD37 and covalently linked via the uncleavable, maleimide-derived thioether-based linker SMCC to the maytansinoid DM1, with potential pro-apoptotic and cytotoxic activities. The antibody moiety of IMGN529 binds to CD37 on tumor B-cells and induces an antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), thereby showing pro-apoptotic activity. In addition, after the internalization of this agent and lysosomal degradation, the DM1 moiety binds to tubulin and inhibits tubulin polymerization and microtubule assembly, resulting in a disruption of microtubule activity and cell division, and eventually causing cell death in CD37-positive B-cells. CD37, a transmembrane glycoprotein, is overexpressed in B-cell malignancies. Compared to reducible, cleavable linkers, the non-reducible SMCC linker shows increased stability in plasma.
A balloon type pouch or bulge in the wall of a cerebral vein.
Atrioventricular septal defect in which the atrioventricular junction is shared evenly between the left ventricle and right ventricle.
Atrioventricular septal defect in which there is usually a single dominant ventricle and a hypoplastic ventricle.
A congenital heart defect in which the heart is located in the right side and the other organs are in their normal position.
The blockage of bowel contents from evacuation; the causes are attributable to non-structural impediments, such as chemical imbalances or the side effects of medications, narcotics in particular.
A stage of retinopathy of prematurity characterized by the presence of the following in at least two quadrants around the optic nerve: dilation and tortuosity of major retinal vasculature as a result of increased blood flow.
An herbal supplement containing an extract from guarana (Paullinia cupana), a climbing plant of the Sapindaceae family which is native to the Amazon basin, with stimulant, antioxidant and potential chemoprotective activities. Guarana supplement contains various phytochemicals, including caffeine, theobromine, theophylline, tannins, saponins, catechins, epicatechins, proanthocyanidols and other compounds in minor concentrations. Caffeine is a central nervous system stimulant and may reduce chemotherapy-related fatigue. Tannins and other polyphenols may have chemopreventive activity. Intake of the guarana supplement may prevent cancer-related anorexia. In addition, animal studies have demonstrated that the ingestion of guarana resulted in decreased proliferation and increased apoptosis of tumor cells.
A synthetic glucagon-like peptide-2 (GLP-2) analogue with potential antidiarrheal and intestinotrophic activities. Upon subcutaneous administration, elsiglutide, a 39 amino acid polypeptide, binds to GLP-2 receptors and thereby promotes proliferation of epithelial cells. Regeneration of endothelial cells damaged during chemotherapy may prevent or decrease chemotherapy-induced diarrhea. In addition, elsiglutide may prevent chemotherapy-induced intestinal injury. GLP-2, a peptide hormone primarily produced in the small intestines in response to food, plays a key role in intestinal epithelial growth, metabolism and regeneration of epithelial cells.
An active metabolite of NV-128, a novel flavonoid small molecule inhibitor of the mammalian Target of Rapamycin (mTOR), with potential antineoplastic activity. Upon administration, mTOR1/2 Kinase inhibitor ME-344 downregulates the PIK3/AKT/mTOR pathway and results in chromatin condensation in the absence of caspase activation. Consequently, this agent induces caspase-independent cell death in tumor cells with a de-regulated PIK3/AKT/mTOR pathway or chemotherapeutic resistant cells.
A deletion of exons 2-7 of the EGFR gene corresponding to 804 nucleotides starting at position 334 through position 1137.
A sensation of great anguish and suffering.
A sensation of discomfort or distress that is bothersome and irritating.
A sensation of extreme discomfort and anguish that is perceived as severe enough to cause one's death.
A sensation of discomfort or distress that renders an individual unable to find any happiness.
A sensation of discomfort or distress that is frightening or scary.
A sensation of having discomfort or distress inflicted upon an individual.
A sensation of extreme discomfort and anguish that is overwhelming and unendurable.
A sensation of discomfort or distress that is very unpleasant.
A sensation of discomfort or distress from excess weight or pressure on a specific anatomical location.
An intense sensation of discomfort or distress that feels like being torn or ripped apart.
A congenital heart defect in which there is an abnormal arrangement of any of the primary blood vessels of the heart in conjunction with the notable absence of any pathologic opening between the cardiac ventricles.
A congenital heart defect in which there is an abnormal arrangement of any of the primary blood vessels of the heart in conjunction with a pathologic opening between the cardiac ventricles.
A rare congenital abnormality characterized by the complete absence of ocular tissue in both orbits.
A rare congenital abnormality characterized by the complete absence of ocular tissue in one orbit.
A congenital abnormality characterized by the presence of one abnormally small eye globe and one normally sized eye globe.
Cataracts in both eyes that result from the aging process, an injury, or as a manifestation of a systemic disorder.
A cataract in one eye that results from the aging process, an injury, or as a manifestation of a systemic disorder.
Cataract in one eye that is present at birth.
An electrocardiographic finding of a tachycardia that originates in the ventricles that is present at birth.
A disorder present at birth characterized by an electrocardiographic finding of a tachycardia that originates above the ventricles.
Damage to the phrenic nerve that results in paralysis of the hemidiaphragm at birth.
A congenital abnormality in the cervical region of the spine in which the meninges protrude through a defect in the spinal column.
A congenital abnormality in the lumbar region of the spine in which the meninges protrude through a defect in the spinal column.
A congenital abnormality in the thoracic region of the spine in which the meninges protrude through a defect in the spinal column.
A lesion found in the division of a vessel into at least two branches, each of which is 1.5 mm or greater in diameter. (ACC)
An unexpected or dangerous reaction to a substance (e.g., food, environmental agent). (ACC)
Penetration of a lead through a systemic vein, coronary vein, or the myocardium. (ACC)
Acute occlusion of a peripheral blood vessel resulting from intravascular migration of material. Examples of embolic material include thrombus, fat, bone marrow, air, and amniotic fluid. (ACC)
Pathology involving the main renal arteries or extrarenal arterial branches. (ACC)
Allogeneic T-lymphocytes transduced with a modified lentiviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment) and the zeta chain of the TCR/CD3 complex (CD3-zeta), coupled to the signaling domain of 4-1BB (CD137), with potential immunomodulating and antineoplastic activities. Upon transfusion, CD19CAR-CD3zeta-4-1BB-expressing allogeneic T-lymphocyte cells direct the T-lymphocytes to CD19-expressing tumor cells, thereby inducing a selective toxicity in CD19-expressing tumor cells. The 4-1BB co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19 and the inclusion of this signaling domain may increase the antitumor activity compared to the inclusion of the CD3-zeta chain alone. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.
A pegylated, recombinant form of L-asparaginase derived from the bacterium Erwinia chrysanthemi (mPEG-R-Crisantaspase), with potential antineoplastic activity. Upon intravenous administration of pegylated recombinant L-asparaginase Erwinia chrysanthemi, asparaginase hydrolyzes L-asparagine to L-aspartic acid and ammonia, thereby depleting cancer cells of asparagine thus blocking protein synthesis and tumor cell proliferation. Asparagine is critical to protein synthesis in cancer cells, which cannot synthesize this amino acid due to the absence of the enzyme asparagine synthase. Compared to other available Erwinia chrysanthemi derived L-asparaginase agents, the pegylated form is longer acting and less immunogenic.
An orally available, multivalent herbal formulation containing a novel mixture of whole extracts from three commonly used Chinese medicinal herbs Ganoderma lucidum (lingzhi mushroom), Salvia miltiorrhiza (Chinese sage, or danshen) and Scutellaria barbata (ban zhi lian), with potential immunomodulating, antiangiogenic, anti-inflammatory, antiproliferative and antiviral activities. Although the exact mechanism of action remains to be fully elucidated due to the complexity of the multiple phytochemicals, multifunctional/multitargeted anticancer agent OMN54 appears to work in an additive and synergistic manner by acting on a variety of signaling pathways and on multiple targets, such as vascular endothelial growth factor, nuclear factor kappa B, interleukin-1beta, fibroblast growth factor, and epidermal growth factor.
A cancer vaccine comprised of a 43 amino acid epitope from glycoprotein MUC1 (mucin 1) and the synthetic Toll-like receptor 4 (TLR-4) agonist PET lipid A encapsulated in cholesterol/dipalmitoylphosphatidylcholine (DPPC)/dimyristoylphosphatidylglycerol (DMPG) liposomes, with potential immunostimulatory and antineoplastic activities. The MUC1 epitope is composed of two 20 amino glycosylated VNTR (various number tandem repeats) from human MUC1A and including 6 glycosylated sites modified by Tn (alfa-N-acetyl-D-galactosamine). Immunization of liposomal MUC1/PET-lipid A vaccine results in an antibody as well as a cytotoxic T-lymphocyte (CTL) response against hypoglycosylated MUC1 expressing tumor cells. The tumor associated antigen MUC1, a type I transmembrane protein, is overexpressed and aberrantly glycosylated in a variety of tumor cells. As a vaccine adjuvant, PET lipid A, also known as penta erythritol lipid A, stimulates both cellular and humoral responses to the vaccine antigen.
A supplement containing lactoferrin derived from bovine milk with potential chemopreventive, immunostimulating, and antimicrobial activity. Upon administration, lactoferrin binds to metal in the oral cavity and may prevent metal-induced oxidation of lipids. This may reduce the metallic taste and taste disturbances induced by certain metal-containing chemotherapeutics; metal-induced lipid oxidation, and the subsequent production of aldehydes and ketones attribute to the metallic smell. Lactoferrin, a glycoprotein belonging to the transferrin family of metal-binding proteins, can be found in milk and other secretory fluids as well as in polymorphonuclear cells and leukocytes; lactoferrin plays a role in the innate defense of mucosal surfaces and its iron-binding activity is associated with the antibacterial activity.
A congenital abnormality characterized by the underdevelopment of one optic nerve.
Generalized depression of the central nervous system of an infant during the perinatal period.
Ischemic necrosis of the spinal cord due to spinal artery occlusion during the birthing process.
The diagnosis assigned when a health care practitioner feels strongly the patient has necrotizing enterocolitis, but lacks definitive proof.
A pathologic fibrous band that impedes passage of intestinal contents through the ileum.
A pathologic fibrous band that impedes passage of intestinal contents through the jejunum.
A pathologic fibrous band that impedes passage of intestinal contents through the colon.
An immature state in which retinopathy of prematurity cannot be established.
Any deviation from normal in the coronary vasculature.
A pathologic fibrous net that impedes passage of intestinal contents through the colon.
Partial or complete paralysis of the facial muscles of one side of an individual's face that is caused by trauma.
Respiratory distress in the newborn due to inhalation of blood; this is an unusual event and is sometimes linked to the non passage of meconium before delivery or mothers with antepartum hemorrhage.
A rare congenital heart anomaly in which there is coexistence of tetralogy of Fallot and complete atrioventricular septal defect. The latter is characterized by defects in the atrial and ventricular septa and a common atrioventricular valve.
A congenital defect in which there is an abnormal spatial arrangement of the internal thoraco-abdominal organs; this manifestation of the disorder presents with many accessory spleens instead of one.
A congenital defect in which there is an abnormal spatial arrangement of the internal thoraco-abdominal organs; in this manifestation of the disorder, the spleen is absent.
Impaired gas exchange by the respiratory system resulting in hypoxemia and decreased oxygenation of the tissues that may be associated with increased arterial levels of carbon dioxide; the respiratory failure is due to a neuromuscular disorder.
Impaired gas exchange by the respiratory system resulting in hypoxemia and decreased oxygenation of the tissues that may be associated with increased arterial levels of carbon dioxide; the respiratory failure is due to a central nervous system disorder.
The formation of a thrombus in the artery as a direct result of an activity associated with vascular access.
The formation of a thrombus in the vein as a direct result of an activity associated with vascular access.
An IgG1 chimeric monoclonal antibody agonist of the cell surface receptor CD40 with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, anti-CD40 monoclonal antibody Chi Lob 7/4 binds to CD40 on a variety of immune cell types, triggering the cellular proliferation and activation of antigen-presenting cells (APCs), activating B cells and T cells, and enhancing the immune response; in addition, this agent binds to the CD40 antigen present on the surfaces of some solid tumor cells, resulting in complement-dependent cytotoxicity (CDC) and antibody-dependent cytotoxicity (ADCC) eventually resulting in decreased tumor growth. CD40, a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on various immune cells, many B-cell malignancies, and many solid tumors, mediating both indirect tumor cell death through the activation of the immune system and direct tumor cell apoptosis.
A recombinant anaerobic bacterium, Bifidobacterium longum, encoding the cytosine deaminase (CD) gene with potential antineoplastic adjuvant activity. Upon injection, the CD-expressing bifidobacterium preferentially localizes and grows in the hypoxic environment of the tumor and expresses CD, an enzyme that catalyzes the intracellular conversion of the prodrug flucytosine (5-FC) into the antineoplastic agent 5-fluorouracil (5-FU). Upon administration of 5-FC, and subsequent localized conversion into 5-FU and its cytotoxic active metabolites, the tumor is specifically exposed to cytotoxic agents while the exposure to normal tissues is minimal.
A proprietary, orally available, small molecule and thalidomide analog, with potential immunomodulating and antineoplastic activity. CC-11006 appears to have a similar mechanism to thalidomide and may modulate the expression of proinflammatory and regulatory cytokines.
An orally available nutritional supplement containing the gamma and delta forms of the vitamin E family member tocotrienol, with hypocholesterolemic, antithrombotic, antioxidant, and potential antineoplastic activity. Upon oral administration, gamma-delta tocotrienol accumulates in cancer cells and may exert their anti-cancer activity in part through 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase downregulation and/or degradation, cell cycle arrest, and induction of caspase-mediated apoptosis. In addition, this agent may inhibit angiogenesis partially through the blockage of vascular endothelial growth factor receptor (VEGFR) and the inhibition of tumor cell-induced vessel formation. Altogether, this may result in the inhibition of tumor cell growth. Further, this agent prevents free radical formation and inhibits lipid peroxidation. Tocotrienols contain 3 double bonds, absent in tocopherols, on its farnesyl isoprenoid side chain that likely contribute to its anti-cancer activities.
A small molecule and orally available inhibitor of colony-stimulating factor-1 receptor (CSF1R; FMS) with potential antineoplastic activity. FMS tyrosine kinase inhibitor JNJ-40346527 blocks the receptor-ligand interaction between FMS and its ligand CSF1, thereby preventing autophosphorylation of FMS. As a result, unphosphorylated FMS can not activate FMS-mediated signaling pathways, thus potentially inhibiting cell proliferation in FMS-overexpressed tumor cells. FMS, a tyrosine kinase receptor, is overexpressed in certain tumor cell types and plays an essential role in macrophage differentiation, recruitment, and activation as well as the regulation of cell proliferation.
An immunoglobulin G1 lambda monoclonal antibody directed against the Notch ligand delta-like 4 (DLL4) with potential antineoplastic activity. Anti-DLL4 monoclonal antibody MEDI0639 specifically binds to DLL4 and prevents its interaction with Notch receptors, thereby inhibiting Notch-mediated signaling and gene transcription, which may block tumor angiogenesis and eventually the inhibition of tumor cell growth. Activation of Notch receptors by DLL4 stimulates proteolytic cleavage of the Notch intracellular domain (NICD); after cleavage, NICD is translocated to the nucleus and mediates the transcriptional regulation of a variety of genes involved in vascular development. The expression of DLL4 is highly restricted to the vascular endothelium; DLL4/Notch signaling is required for the development of functional tumor blood vessels.
An antibody-drug conjugate (ADC) containing a monoclonal antibody directed against guanylyl cyclase C (GCC or GUCY2C) conjugated to monomethylauristatin E (MMAE), an auristatin derivative and a potent microtubule inhibitor, with potential antineoplastic activity. The monoclonal antibody moiety of MLN0264 selectively binds to GCC, a transmembrane receptor normally found on intestinal cells and dopamine neurons in the brain, but is also overexpressed on the surface of gastrointestinal cancers. Upon internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis in GCC-expressing tumor cells.
An inhibitor of transient receptor potential cation channel vanilloid family member 6 (TRPV6, CaT1 or CATL) with potential antineoplastic activity. TRPV6 calcium channel inhibitor SOR-C13 binds to TRPV6 and prevents the influx of calcium ions into TRPV6-expressing tumor cells. This inhibits the activation of nuclear factor of activated T-cell (NFAT) transcription complex which may result in an inhibition of calcium-dependent cancer cell proliferation and an induction of apoptosis in tumor cells overexpressing TRPV6. The TRPV6 ion channel plays a key role in calcium homeostasis and is highly selective for calcium compared to other cations; it is overexpressed in a variety of tumors and initiates tumor cell growth, proliferation and metastases.
A cancer vaccine comprised of human leukocyte antigen (HLA) A2 restricted folate binding protein (FBP) epitope E39 (amino acids 191 to 199), with potential immunostimulatory and antineoplastic activity. Upon intradermal injection, FBP E39 peptide vaccine may induce a specific cytotoxic T-lymphocyte (CTL) response against FBP-expressing tumor cell types. FBP is a membrane-bound, tumor-associated antigen highly overexpressed in various tumor cell types, such as in breast, ovarian and endometrial cancers; E 39 is a strong immunogenic peptide.
An orally available small molecule mitogen-activated protein kinase kinase (MAP2K, MAPK/ERK kinase, or MEK) inhibitor, with potential antineoplastic activity. MEK inhibitor WX-554 selectively binds to and inhibits the activity of MEK, thereby preventing the activation of MEK-dependent effector proteins including some transcription factors, which may result in the inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK, a dual-specificity threonine/tyrosine kinase that plays a key role in the activation of the RAS/RAF/MEK/ERK signaling pathway, is frequently upregulated in a variety of tumor cell types.
Stage I includes: Any T, Any N, M0. M0: No evidence of distant metastasis. (from AJCC 7th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor size 2 cm or less in greatest dimension, limited to the thyroid gland. N0: No regional lymph node metastasis. M0: No evidence of distant metastasis. (from AJCC 7th Ed.)
Stage II includes: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 7th Ed.)
Stage II includes: T2, N0, M0. T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension, limited to the thyroid gland. N0: No regional lymph node metastasis. M0: No evidence of distant metastasis. (from AJCC 7th Ed.)
An electrocardiographic finding that a myocardial infarction has occurred concurrently with the absence of clinical symptoms.
A molecular genetic abnormality that refers to a change in the nucleotide sequence of the PALB2 gene.
A peptide vaccine containing five immunogenic peptide epitopes of the human folate receptor alpha (FR alpha or FOLR1), including FR30, FR56, FR76, FR113, and FR238, with potential immunomodulating and antineoplastic activity. Upon administration, the multi-epitope FR alpha peptide vaccine may induce a cytotoxic T-lymphocyte (CTL) response against FR alpha-overexpressing tumor cells. FR alpha is a high-affinity folate-binding protein and a member of the folate receptor family; this receptor is overexpressed in a majority of ovarian cancers and in about 50% of breast cancers.
A long acting glyco-pegylated recombinant form of human granulocyte colony-stimulating factor (G-CSF), with hematopoietic activity. Similar to G-CSF, lipegfilgrastim binds to and activates specific cell surface receptors, and stimulates neutrophil progenitor proliferation and differentiation. Therefore, this agent may prevent the duration and incidence of chemotherapy-induced neutropenia. Compared to filgrastim, lipegfilgrastim has a prolonged plasma half-life.
An orally available, small molecule inhibitor of AGC group kinases, with potential antineoplastic activity. AT13148 inhibits, in an ATP-competitive manner, the enzymatic activity of two AGC kinases, protein kinase B (PKB or AKT) and p70S6K which play key roles in the PI3K/PKB/mTOR signaling pathway. Blockade of this pathway leads to an inhibition of cell growth and the induction of apoptosis in susceptible tumor cells. PI3K/PKB/mTOR pathway is dysregulated in greater than 50% of tumors, and is often correlated with resistance and increased tumor survival. AGC group kinases are serine/threonine kinases that are regulated by secondary messengers such as cyclic AMP and lipids.
Autologous dendritic cells tranduced with a replication incompetent adenovirus encoding human pro-inflammatory cytokine interleukin-12 (IL-12) (INXN-3001) in combination with the proprietary orally bioavailable, small molecule activator ligand INXN-1001, with potential immunomodulating and antineoplastic activities. Production of IL-12 is controlled by an inducible DNA element that allows transcription initiation only in the presence of the ligand inducer INXN-1001. Upon intratumoral injection of INXN-3001 and subsequent oral administration of activator ligand, INXN-1001 is able to induce expression of IL-12 in INXN-3001. IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells, inducing the secretion of interferon-gamma and inducing a cytotoxic T lymphocyte response against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation. As INXN-1001 regulates both the timing and the levels of IL-12 expression, IL-12 toxicity can be reduced.
A formulation of the 6-omega fatty acid derivative 2'-linoleyl carbonate (LOC) conjugated to paclitaxel, a taxane compound extracted from the Pacific yew tree Taxus brevifolia, with potential antineoplastic activity. Paclitaxel binds to and stabilizes tubulin, thereby interfering with the dynamics of microtubule assembly/disassembly and resulting in the inhibition of cell division. LOC enhances the uptake of paclitaxel by tumor cells, thereby concentrating this agent in tumor cells compared to normal cells, and may decrease its toxicity profile; fatty acids serve as energy sources and biochemical precursors for the fast growing tumor cells.
An aerosol formulation of aldesleukin, a recombinant form of interleukin-2 (IL-2), with potential immunostimulating activity. Upon IL-2 inhalation, this cytokine activates lymphokine-activated killer cells and natural killer cells, and induces expression of cytotoxic cytokines, such as interferon-gamma and transforming growth factor-beta. This may eventually halt tumor cell growth. Localized administration of IL-2 may decrease toxicity and increase efficacy.
An orally bioavailable inhibitor of raptor-mTOR protein complex (TORC1) and rictor-mTOR protein complex (TORC2) with potential antineoplastic activity. TORC1/2 inhibitor DS-3078a binds to and inhibits both TORC1 and TORC2, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation. TORC1 and 2 are upregulated in some tumors and play an important role in the PI3K/Akt/mTOR signaling pathway, which is frequently dysregulated in human cancers.
A population of allogeneic cytotoxic T-lymphocytes (CTLs) specifically reactive to human adenovirus (Ad) with potential immunomodulating and anti-adenoviral activities. Upon immunoprophylactic adoptive cell therapy, infusion of allogeneic Ad-specific CTLs may help reconstitute Ad-specific CTL responses in patients at risk of developing Ad infections after allogeneic stem cell transplant or in Ad-infected immunocompromised hosts. These allogeneic Ad-specific CTLs are prepared by multiple rounds of stimulation with donor peripheral blood mononuclear cells and lymphoblastoid cell lines that have been transduced with Ad5f35, a recombinant adenoviral vector carrying no transgene.
A liposomal formulation consisting of short-interfering RNAs (siRNAs) directed against ephrin type-A receptor 2 (EphA2) and encapsulated into 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) neutral liposomes, with potential antineoplastic activity. Upon internalization, EphA2-targeting DOPC-encapsulated siRNA can hybridize to EphA2 DNA and mRNA, thereby interfering with both the transcription and translation of EphA2, and thus inhibiting tumor cell growth. The cell-surface receptor EphA2, a member of the ephrin family of receptor tyrosine kinases (RTKs) involved in mammalian development, is overexpressed by a variety of different cancer cell types and plays an important role in tumor growth.
An allogeneic cancer vaccine composed of lethally irradiated, whole pancreatic cancer cells transfected with a plasmid carrying the gene for cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Allogeneic GM-CSF-secreting tumor vaccine PANC 6.03 pcDNA-1/GM-Neo secretes GM-CSF thereby activating dendritic cells, promoting antigen presentation to B- and T-cells, and promoting a cytotoxic T-lymphocyte (CTL) response. This may eventually kill tumor cells. The pancreatic tumor cells are derived from the PANC 6.03 tumor cell line.
An allogeneic cancer vaccine composed of lethally irradiated, whole pancreatic cancer cells transfected with a plasmid carrying the gene for cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Allogeneic GM-CSF-secreting tumor vaccine PANC 10.05 pcDNA-1/GM-Neo secretes GM-CSF thereby activating dendritic cells, promoting antigen presentation to B- and T-cells, and promoting a cytotoxic T-lymphocyte (CTL) response. This may eventually kill tumor cells. The pancreatic tumor cells are derived from the PANC 10.05 tumor cell line.
A cancer vaccine composed of HLA-*2402-restricted epitopic peptides derived from three cancer/testis (CT) antigens, with potential antineoplastic activity. Upon subcutaneous administration, HLA-A*2402-restricted multipeptide vaccine S-488410 may elicit a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing these CT antigens. CT antigens, normally expressed only in germ cells of the testis, are overexpressed in a wide variety of human cancers.
A polybisphosphonate dextran-guanidine conjugate with potential anti-resorptive and antineoplastic activities. Alendronic acid and aminoguanidine were conjugated sequentially to oxidized dextran resulting in an average of 8 alendronate and 50 guanidine groups coupled to the dextran backbone. Upon administration, the poly-alendronate dextran-guanidine conjugate inhibits the mevalonate pathway by inhibiting farnesyl diphosphate synthase (FDPS) which leads to a reduction in protein prenylation and to the loss of downstream metabolites essential for osteoclast function. This eventually leads to the induction of apoptosis in osteoclasts. Also, by preventing osteoclast-mediated bone resorption, this agent decreases bone turnover and stabilizes the bone matrix. The guanidine moiety increases the nitrogen content and possibly the activity of the bisphosphonate and its ability to inhibit FDPS. In addition, the guanidine moiety facilitates cell internalization and may contribute to this agent's cytotoxicity.
The lead has been left in situ and reused.
An indication that a study participant has been removed from the study by the parent or legal guardian.
The potential future harm that may arise from some present action or attribute or condition is moderate.
A sustained and substantial impairment or disruption of a person's ability to conduct normal life functions for the remainder of his/her life.
Vaccines that the patient received within four weeks prior to the current vaccine administration date being reported.
A humanized monoclonal antibody (MoAb) directed against the human receptor tyrosine-protein kinase ErbB-3 (HER3) with potential antineoplastic activity. Anti-ErbB3 MoAb AV-203 binds to and inhibits both ligand neuregulin-1 (NRG-1)-dependent and ligand-independent ErbB3 activation, which may result in inhibition of ErbB3-dependent PI3K/Akt signaling and may lead to inhibition of cellular proliferation and differentiation. ErbB3, a member of the epidermal growth factor receptor (EGFR) family, is frequently overexpressed in solid tumors and its overexpression generally correlates with poor prognosis and tumor resistance; it has no active kinase domain itself but is activated through heterodimerization with other members of the EGFR receptor family that do.
A clear, colorless water-based vaginal gel containing the partial benzyl ester of hyaluronic acid (HA) with potential hydrating activity. Upon vaginal application, HA adheres to the vaginal mucosa where it retains water, provides moisture to the vagina and protects the vaginal mucosa. This gel may provide relief in vaginal dryness and may prevent sexual discomfort, itching and irritation. This HA derivative is less susceptible to enzymatic breakdown and provides longer lasting activity compared to HA. HA is naturally present in the vaginal epithelium.
A water-based vaginal lubricant with hydration activity. Upon application to the vagina, the water-based vaginal lubricant provides moisture and may relieve dryness and sexual discomfort.
A preservative-free, prebiotic vaginal lubricant with potential moisturizing and protective activities. Upon vaginal application, the lactoperoxidase/lysozyme/lactoferrin-based prebiotic vaginal lubricant moisturizes the vagina and may relieve and/or prevent dryness, itching, irritation, odor and infection. The vaginal lubricant contains anti-yeast proteins and enzymes, including lactoperoxidase, lysozyme and lactoferrin which are naturally found in vaginal fluid and help maintain the natural microflora in the vagina. The prebiotic glycogen helps restore and maintain the beneficial microorganisms in the vagina and maintains a healthy acidic pH. Altogether, this protects the vagina against the actions of harmful bacteria.
A cancer vaccine composed of a genetically engineered, replication-deficient type 5 adenovirus carrying the human prostate-specific antigen (PSA), with potential immunostimulating and antineoplastic activities. Upon subcutaneous vaccination with the adenovirus-PSA prostate cancer vaccine, the adenovirus infects cells and expresses PSA. In turn, PSA may activate the immune system and may induce a cytotoxic T-lymphocyte response against PSA-expressing tumor cells. PSA, a tumor associated antigen, is expressed by prostate epithelial cells and is overexpressed in prostate cancer.
A nutritional supplement containing the active metabolite of the essential amino acid leucine, with potential anti-catabolic and anabolic activities. Upon oral administration of beta-hydroxy-beta-methylbutyrate (HMB), this leucine metabolite may decrease protein breakdown and increase protein synthesis thereby increasing muscle strength and mass. Although the exact mechanisms remain to be fully elucidated, multiple mechanisms have been proposed: 1) HMB is a precursor of cholesterol synthesis in skeletal muscle cells thereby increasing sarcolemmal integrity; 2) HMB may inhibit the ubiquitin-proteasome proteolytic pathway responsible for the specific degradation of intracellular proteins, thereby preventing muscular proteolysis; and/or 3) HMB may stimulate protein synthesis through a mammalian target of rapamycin (mTOR)-mediated mechanism.
A skin care treatment system consisting of a cytokine-containing milk-based cooling gel and a cytokine-containing milk-based soothing lotion with hydrating and potential protective activity against radiation-induced dermatitis. Application of the R1 cooling gel immediately upon radiation treatment may hydrate the skin, provide cooling relief, and may protect the skin against radiation-induced dermatitis. The subsequent application of the R2 lotion moisturizes the skin while also protecting the skin against inflammation. In addition, R2 contains avobenzone, homosalate, octinoxate and octocrylene, which exert UVA and UVB skin protective activity.
The result of an actual line of questioning about a sign, symptom, disease, or other medical occurrence.
A proprietary fusion protein comprised of the cysteine-rich domain of frizzled family receptor 8 (Fzd8) fused to the human immunoglobulin Fc domain with potential antineoplastic activity. Upon intravenous administration, ipafricept competes with the membrane-bound Fzd8 receptor for its ligand, Wnt proteins, thereby antagonizing Wnt signaling. This may result in the inhibition of Wnt-driven tumor growth. Fzd8, a member of the Frizzled family of G protein-coupled receptors, is one of the components in the Wnt/beta-catenin signaling pathway that plays key roles in embryogenesis and cancer growth.
A probiotic containing the non-pathogenic yeast Saccharomyces boulardii with antidiarrheal and potential anti-inflammatory, antimicrobial and immunomodulating activities. As a dietary supplement, S. boulardii may improve digestion and help maintain adequate colonization of the gastrointestinal (GI) tract by modulating the composition of the normal intestinal microflora. During colonization of the GI tract, S. boulardii forms a protective barrier that helps maintain the integrity of the epithelial barrier. This prevents attachment of pathogens to the intestinal mucosa. In addition, this probiotic secretes a protease that binds to and degrades toxins A and B produced by Clostridium difficile, thereby preventing their harmful effects. Dietary supplementation with this bacterium may reduce the secretion of proinflammatory cytokines and may potentiate natural and acquired immunity.
A recombinant fusion protein composed of the full-length extracellular domain (soluble) of human receptor tyrosine kinase ephrin type-B receptor 4 (sEphB4) and fused, at its C-terminus, to full-length human serum albumin (HSA), with potential antineoplastic and anti-angiogenic activities. sEphB4-HSA functions as a decoy receptor for the membrane-bound ligand Ephrin-B2 (Efnb2) and interferes with the binding of Efnb2 to its native receptors, including EphB4 and EphA3. This may result in a reduction of angiogenesis and a reduction in cell growth of Efnb2 and/or EphB4 over-expressing tumor cells. In addition, this agent also prevents the angiogenic effects of numerous growth factors due to interactions between Efnb2 and EphB4. Efnb2 and EphB4 are overexpressed in a variety of tumor cell types; the bi-directional signaling of Efnb2-EphB4 plays an important role in angiogenesis and tumor cell migration, invasion, and proliferation. Albumin reduces this agent's degradation, improves circulation time and may thus improve efficacy.
An extremely rare adenosarcoma that arises from the uterine ligament.
An electrocardiographic finding of pathologic Q waves with accompanying ST elevation in leads V3 through V6, which is suggestive of acute myocardial infarction of the anterolateral wall of the left ventricle. (CDISC)
An electrocardiographic finding of pathologic Q waves with accompanying ST elevation in leads V1 through V4, which is suggestive of acute myocardial infarction of the anteroseptal wall of the left ventricle. (CDISC)
An electrocardiographic finding of pathologic Q waves with accompanying ST elevation in leads I and aVL, which is suggestive of acute myocardial infarction of the high lateral wall of the left ventricle. (CDISC)
An electrocardiographic finding in leads V1 or V2 of an initial R wave duration greater than or equal to 40 ms, R wave greater than S wave, upright T wave, with accompanying ST elevation, which is suggestive of acute myocardial infarction of the ventricular wall of the left ventricle. Evidence of inferior or lateral myocardial infarction is usually also present. (CDISC)
An electrocardiographic finding of pathologic Q waves with accompanying ST elevation in leads V1, V2 and often V3, which is suggestive of acute myocardial infarction of the intraventricular septum. (CDISC)
An electrocardiographic finding in which two premature atrial complexes occur sequentially. (CDISC)
There are no indicators of bacterial infection in an individual who previously had an infection.
There are indicators of bacterial infection in the individual who previously had an infection.
Objective evidence of bacterial infection perceptible to the examiner by laboratory procedure.
There are no signs or symptoms of disease in the individual who previously had a disease.
There are still signs or symptoms of disease in the individual who previously had an infection.
An electrocardiographic finding where the amplitude of the R wave becomes greater than the amplitude of the S wave in the QRS complex at an unusually early point in the precordial leads, usually in leads V1 or V2. (CDISC)
Resistance to nearly all known drugs, particularly the most efficacious or non-first line drugs, used in the treatment of a particular disease.
An electrocardiographic finding of a frontal plane QRS axis from -90 to +180 degrees. (CDISC)
A lack of response to the first cycle of therapy.
A lack of response to more than one cycle of therapy.
A patient's failure to remember to take a dose of medication.
An electrocardiographic finding that occurs when electrical activation of the atria or ventricles occurs from two separate sites. This results in a P wave or QRS complex that displays merged characteristics of beats originating from the two different sites. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads I and aVL, which is suggestive of myocardial infarction of the high lateral wall of the left ventricle. (CDISC)
An electrocardiographic finding where the amplitude of the R wave does not become greater than the amplitude of the S wave until an unusually late point in the precordial leads, usually in leads V4 to V6. (CDISC)
An electrocardiographic finding suggestive of a hypertrophied left ventricle, characterized by large QRS amplitudes, ST depression and T wave inversion. (CDISC)
The medication is no longer held or possessed by the subject and is incapable of being recovered or regained.
Medications that were lost because they were put in the wrong place.
An electrocardiographic finding of premature atrial complexes which have 2 or more distinct morphologies, suggesting origin at more than one atrial site. (CDISC)
An electrocardiographic finding of an atrial tachycardia which terminates in less than 30 seconds. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V3 and V4, which is suggestive of myocardial infarction of the anterior wall of the left ventricle, without evidence of current or ongoing acute infarction. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V3 through V6, which is suggestive of myocardial infarction of the anterolateral wall of the left ventricle, without evidence of current or ongoing acute infarction. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V1 through V4, which is suggestive of myocardial infarction of the anteroseptal wall of the left ventricle, without evidence of current or ongoing acute infarction. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V1 to V6, I and aVL, which is suggestive of myocardial infarction involving the anterior and anterolateral walls of the left ventricle, without evidence of current or ongoing acute infarction. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads I and aVL, which is suggestive of myocardial infarction of the high lateral wall of the left ventricle, without evidence of current or ongoing acute infarction. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads III, aVF and often II, which is suggestive of myocardial infarction of the inferior wall of the left ventricle, without evidence of current or ongoing acute infarction. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V5, V6, I and aVL, which is suggestive of myocardial infarction of the lateral wall of the left ventricle, without evidence of current or ongoing acute infarction. (CDISC)
An electrocardiographic finding in leads V1 or V2 of an initial R wave duration greater than or equal to 40 ms, R wave greater than S wave, and upright T wave, which is suggestive of myocardial infarction of the posterior wall of the left ventricle, without evidence of current or ongoing acute infarction. Evidence of inferior or lateral myocardial infarction is usually also present. (CDISC)
An electrocardiographic finding, in the presence of an old or age indeterminate inferior wall myocardial infarction, of Q waves greater than or equal to 40 ms in duration in the right ventricular leads V4R through V6R. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V1, V2 and often V3, which is suggestive of myocardial infarction of the intraventricular septum, without evidence of current or ongoing acute infarction. (CDISC)
A previous episode of failure by a patient to follow medical advice, take medication as directed, or adhere to a prescribed course of treatment.
An electrocardiographic finding in which the frontal plane QRS axis cannot be calculated.
An electrocardiographic finding of ST depression and T wave inversion in the presence of increased QRS amplitude which are thought to be due to left ventricular hypertrophy.
An electrocardiographic finding of a QT interval corrected for heart rate that is shorter than the lower limit of normal. Thresholds for different age, gender, and patient populations exist. (CDISC)
A drug serum concentration below therapeutic levels.
An electrocardiographic finding of premature atrial complexes which have a single distinct morphology, suggesting origin at one atrial site.
An electrocardiographic finding of pathologic Q waves, which is suggestive of myocardial infarction of one or more regions of the heart and which is new compared to prior ECGs. No specification is provided for localization. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V3 and V4, which is suggestive of myocardial infarction of the anterior wall of the left ventricle and which is new compared to prior ECGs. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V3 through V6, which is suggestive of myocardial infarction of the anterolateral wall of the left ventricle and which is new compared to prior ECGs. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V1 through V4, which is suggestive of myocardial infarction of the anteroseptal wall of the left ventricle and which is new compared to prior ECGs. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V1 to V6, I and aVL, which is suggestive of myocardial infarction involving the anterior and anterolateral walls of the left ventricle and which is new compared to prior ECGs. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads I and aVL, which is suggestive of myocardial infarction of the high lateral wall of the left ventricle and which is new compared to prior ECGs. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads III, aVF and often II, which is suggestive of myocardial infarction of the inferior wall of the left ventricle and which is new compared to prior ECGs. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V5, V6, I and aVL, which is suggestive of myocardial infarction of the lateral wall of the left ventricle and which is new compared to prior ECGs. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V1, V2 and often V3, which is suggestive of myocardial infarction of the intraventricular septum and which is new compared to prior ECGs. (CDISC)
An extended release (ER) injectable formulation composed of the hydrochloride salt form of bupivacaine, an amide-type, long-acting local anesthetic, in a resorbable sucrose acetate isobutyrate-based matrix, with analgesic activity. Following administration in or around a specific site, ER bupivacaine is released from the matrix over an extended period of time. Upon release, bupivacaine reversibly binds to specific voltage-gated sodium ion channels in the neuronal membrane, resulting in a decrease in the voltage-dependent membrane permeability to sodium ions, membrane destabilization, and depolarization inhibition thus disrupting nerve impulse conduction. This eventually leads to a reversible loss of sensation. This formulation may provide pain relief up to 72 hours.
An orally available small molecule inhibitor of the nuclear enzymes poly (ADP-ribose) polymerase (PARP) 1 and 2, with potential antineoplastic activity. Upon administration, E7449 selectively binds to PARP 1 and 2, thereby preventing the repair of damaged DNA via the base excision repair (BER) pathway. This agent enhances the accumulation of single and double strand DNA breaks and promotes genomic instability eventually leading to apoptosis. PARP 1/2 inhibitor E7449 may enhance the cytotoxicity of DNA-damaging agents and of radiotherapy. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA.
A derivative of pyridoxyl ethyldiamine (PLED) and mimetic of the human mitochondrial manganese superoxide dismutase (MnSOD), with antioxidant, metal chelating and potential chemoprotective activities. Upon administration, PLED-based MnSOD mimetic mimics MnSOD and scavenges oxygen free radicals such as superoxide anion, hydrogen peroxide, and hydroxyl radical, thereby preventing oxygen free radical damage to macromolecules such as DNA and minimizing oxygen free radical-related chemotoxicity in normal tissues. In addition, this agent is able to strongly bind to iron.
A proprietary suspension formulation prepared from granules of standardized extracts from the fruits of Vaccinium myrtillus, the aerial parts of Macleaya cordata and the roots of Echinacea angustifolia, with potential anti-mucositis, anti-inflammatory, and analgesic activities. The main active ingredients of this formulation include anthocyanosides and procyanidins, benzophenanthridinic alkaloids, and alkylamides from V. myrtillus, M. cordata and E. angustifolia extracts, respectively. Upon administration in the mucosal cavity, the anthocyanosides scavenge free radicals, form a protective barrier on the mucosa, and protect the integrity of the capillary vessels; the benzophenanthridine alkaloids prevent the production of pro-inflammatory cytokines by inhibiting NF-kB and may halt the growth of microorganisms; the alkylamides inhibit cyclooxygenase and 5-lipoxygenase thereby blocking productions of prostaglandin and leukotriene. Furthermore, alkylamides modulate the expression of tumor necrosis factor alpha and other cytokines involved in inflammation processes through cannabinoid type 2 receptors and as cannabinomimetics they may also exert analgesic activity.
A low molecular weight heparin derivative and heparan sulfate proteoglycan (HSPG) mimetic with no or minimal anticoagulant activity and potential antineoplastic activities. Upon administration, M402 mimics HSPGs by binding to and inhibiting various heparin-binding growth factors, chemokines, and cytokines such as VEGF, HGF, FGF2, SDF-1a, heparanase and P-selectin all of which are essential for tumor angiogenesis and metastasis to occur. This inhibits heparin binding growth factor-mediated signaling and disrupts tumor-stromal interactions eventually leading to an inhibition of angiogenesis and tumor cell progression. In addition, M402 may enhance the cytotoxic effect of other chemotherapeutic agents.
A peptide cancer vaccine comprised of a peptide derived from Wilms tumor gene 1 (WT1) protein, with potential immunomodulating and antineoplastic activities. Upon administration, WT2725 may induce a specific cytotoxic T-lymphocyte (CTL) response against WT1-overexpressing tumor cells. WT1 protein, a zinc finger DNA-binding protein, is overexpressed in leukemic cells and in a vast number of non-hematological solid tumors.
A pyrimidine analogue and a proprietary prodrug based on an aryloxy phosphoramidate derivative of gemcitabine with potential antineoplastic activity. Upon intravenous administration and cellular uptake, NUC-1031 is converted into the active metabolites difluorodeoxycytidine di- and triphosphate (dFdCDP, dFdCTP). dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA replication; dFdCTP is incorporated into DNA, resulting in premature termination of DNA replication and eventually induction of apoptosis. With the phosphoramidate moiety on the gemcitabine monophosphate group, NUC-1031 has improved properties over its parent molecule: 1) is more lipophilic and accumulates in cancer cells by passive diffusion and does not require a nucleoside transporter, 2) as the agent is delivered in the monophosphate form, the first phosphorylation step by deoxycytidine kinase is not required, 3) this agent is not susceptible to deactivation by cytidine deaminase cleavage of the monophosphorylated form. Altogether, this may help overcome resistance to gemcitabine.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) transduced with a recombinant adenoviral vector encoding three full length human melanoma associated antigens (MAAs), tyrosinase, melan-A (MART-1) and the melanoma antigen A6 (MAGEA6), with potential antineoplastic activity. Upon intradermal administration, adenovirus encoding tyrosinase/MART-1/MAGEA6-transduced autologous DC vaccine may stimulate a cytotoxic T lymphocyte (CTL) response against tyrosinase/MART-1/MAGEA6-positive tumor cells, which may result in tumor cell death and decreased tumor growth. Tyrosinase, a melanoma-specific differentiation antigen, catalyzes the first step of melanin synthesis in melanocytes. Vaccination with multi-antigen modified DC may improve the efficacy of the DC immunotherapy.
A Chinese herbal medicine composed of extracts from the roots of Panax Ginseng (ren shen) and Ophiopogon japonicas (mai men dong), and the berries of Schisandra chinensis (wu wei zi) with potential protective activity. Ginseng contains a complex mixture of saponins, ginsenosides and panaxosides; homoisoflavonoids isolated from Ophiopogon show anti-inflammatory properties; Schisandra contains abundant amounts of phytoestrogen lignans with antioxidant activity. Although the mechanism of action maybe inexplicit or complex, these phytochemicals work synergistically and may improve symptoms such as shortness of breath, sweating, cough, thirst, dry mouth, and palpitations as well as have an effect on chemotherapy or radiotherapy-induced fatigue, weakness, and neutropenia.
A powder-based, probiotic supplement drink containing the non-pathogenic microorganisms Lactobacillus plantarum 299v, Lactobacillus acidophilus, and Bifidobacterium lactis, with potential immunomodulating and protective activities. Upon oral ingestion, the naturally-occurring bacterial components in this dietary supplement may improve digestion and help maintain adequate colonization of the gastrointestinal (GI) tract by modulating the composition of the normal microflora. During colonization in the GI tract, the bacteria may form a protective intestinal barrier which may prevent damage to the mucosal epithelia caused by toxins and attachment of potential pathogens, thereby protecting against infections. In addition, this agent may reduce the secretion of proinflammatory cytokines and may potentiate natural and acquired immunity.
A cancer vaccine containing autologous dendritic cells pulsed with a fusion product of an epitope of human tumor-associated epithelial mucin 1 (MUC1) antigen and the vaccine adjuvant mannan (oxidized mannose), with potential antineoplastic activity. When the modified dendritic cells are returned to the patient, they may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells positive for the MUC1 antigen, resulting in tumor cell lysis. Addition of manna in this vaccine, enhances immune recognition. MUC1 antigen, a high-molecular-weight transmembrane glycoprotein, is overexpressed on many tumor cells.
A therapeutic DNA vaccine encoding the E6/E7 fusion protein of human papillomavirus (HPV) subtypes 16 and 18, plus the immune-enhancer, Fms-like tyrosine kinase-3 ligand (FLT3L), with potential immunostimulating and antineoplastic activities. DNA vaccine GX-188E is administered using a proprietary delivery system that electroporates the vaccine into cervical cells. Expression of the E6/E7 fusion product may elicit a cytotoxic T-lymphocyte (CTL) response against cervical cancer cells expressing E6 and E7 oncoproteins, resulting in tumor cell lysis. FLT3L is a ligand for the FLT3 tyrosine kinase receptor, which upon activation stimulates the proliferation of hematopoietic progenitor cells. HPV type 16 and 18 are the most common HPV types involved in cervical carcinogenesis.
Localized tumor with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumor microscopically. (cancer.gov)
Localized tumor with or without complete gross excision, with ipsilateral nonadherent lymph nodes positive for tumor. Enlarged contralateral lymph nodes must be negative microscopically. (cancer.gov)
An isotonic, sterile, absorbable adhesion barrier gel composed of polyethylene oxide and sodium carboxymethylcellulose, with protective activity. Upon application of a single layer into the uterine cavity at the end of any hysteroscopic surgery, the absorbable adhesion barrier gel may provide a protective barrier which protects the traumatized tissue and allows for healing. This gel may therefore prevent the formation of post-surgical intrauterine adhesions.
An orally available, small molecule inhibitor of vascular endothelial growth factor receptors (VEGFRs), with potential anti-angiogenic and antineoplastic activities. Upon oral administration, fruquintinib inhibits VEGF-induced phosphorylation of VEGFRs 1, 2, and 3 which may result in the inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and tumor cell death. Expression of VEGFRs may be upregulated in a variety of tumor cell types.
A monoclonal antibody directed against transforming growth factor-beta receptor type II (TGF-beta RII) with potential antineoplastic activity. Anti-TGF-beta RII monoclonal antibody IMC-TR1 specifically targets and binds to TGF-beta R11, thereby preventing the activation of TGF-beta RII-mediated signaling pathways. TGF-beta RII is mutated in a number of cancer cell types and is involved in cancer cell proliferation and tumor progression.
An orally available inhibitor of the steroid 17-alpha-hydroxylase/C17,20 lyase (CYP17A1 or CYP17), with potential antiandrogen and antineoplastic activities. Upon oral administration, CYP17 inhibitor CFG920 inhibits the enzymatic activity of CYP17A1 in both the testes and adrenal glands, thereby inhibiting androgen production. This may decrease androgen-dependent growth signaling and may inhibit cell proliferation of androgen-dependent tumor cells. The cytochrome P450 enzyme CYP17A1, localized to the endoplasmic reticulum, exhibits both 17alpha-hydroxylase and 17,20-lyase activities, and plays a key role in the steroidogenic pathway that produces steroidal hormones.
Any of the synthetic, long-acting hematopoietic growth factors that stimulate the growth of myeloid cells.
Any of the synthetic, short-acting hematopoietic growth factors that stimulate the growth of myeloid cells.
Any disease or disorder of relevance that occurs before, during or after another illness.
A malignant germ cell tumor other than dysgerminoma that arises from the ovary.
A human papillomavirus (HPV) type 16 vaccine containing four E6 peptides in combination with the extract of Candida albicans, with potential immunomodulating activity. Upon administration of HPV-16 E6 peptides vaccine/Candida albicans extract, the four HPV-16 E6 peptides and the candida albicans may activate the immune system to mount a cytotoxic T lymphocyte (CTL) response against cells expressing the E6 oncoprotein, resulting in tumor cell lysis. The HPV 16 transforming protein E6 is expressed in precancerous and malignant cervical lesions. Candida albicans allergenic extract may be used as a recall antigen to stimulate the immune system against HPV.
A formulation of nanoparticles encapsulating the hydrochloride salt form of the anthracycline antibiotic doxorubicin, with potential antitumor activity. Upon intravenous administration, doxorubicin intercalates DNA, interferes with the activity of topoisomerase II, and causes DNA adducts and other DNA damage, resulting in tumor cell growth inhibition and apoptosis. This agent also interacts with cell membrane lipids causing lipid peroxidation. Delivery of doxorubicin in nanoparticles may improve drug penetration into tumors and may circumvent the tumor cells multidrug resistance mechanisms and may therefore be effective in chemoresistant tumor cells.
A vaccine containing multiple peptides derived from the human telomerase reverse transcriptase (hTERT), survivin and cytomegalovirus (CMV), with potential immunostimulating and antineoplastic activities. Upon administration, hTERT/survivin/CMV multipeptide vaccine may elicit a cytotoxic T cell (CTL) response against tumor cells espressing hTERT, survivin and CMV. hTERT, the catalytic subunit of telomerase, and the inhibitor of apoptosis (IAP) family member survivin, both often upregulated in tumor cells, play key roles in tumor cell growth and survival. Further, CMV expression is correlated with certain types of cancer.
A water-soluble, small molecule and activator of the tumor suppressor protein p53, with potential antineoplastic activity. Upon intravenous administration, thioureidobutyronitrile activates p53 which in turn induces the expressions of p21 and PUMA (p53 up-regulated modulator of apoptosis), thereby inhibiting cancer cell growth and causing tumor cell apoptosis. Thioureidobutyronitrile may be effective in drug-resistant cancers with mutated p53. p53 tumor suppressor, a transcription factor regulating the expression of many stress response genes and mediating various anti-proliferative processes, is often mutated in cancer cells.
A non-radioactive, naturally occurring carbon 13 (13C) glucose isotopomer in which all six carbons are 13C, with potential imaging application. Upon administration of uniformly-labeled [U-13C] glucose, the glucose is taken up and metabolized by tumors and the 13C-containing metabolites can be imaged by 13C nuclear magnetic resonance (NMR) spectroscopy. Since tumor cells take up and metabolize glucose in higher amounts and through different pathways than normal cells, this agent may help assess the metabolic phenotype of the tumor.
A malignant neoplasm caused by human papillomavirus in an a patient with a history of AIDS.
An anaplastic astrocytoma (grade III astrocytic tumor) or glioblastoma (grade IV astrocytic tumor).
An orally bioavailable small molecule tyrosine kinase inhibitor that targets both Abl and Src kinases with potential antineoplastic activity. Upon oral administration, AZD0424 selectively inhibits both Src and Abl kinase activity which may result in the inhibition of tumor growth in susceptible tumor cells. Src and Abl kinases are upregulated in certain tumor cells and play important roles in tumor cell proliferation and metastasis.
A cell based cancer vaccine composed of mature polarized dendritic cells (DCs) and pulsed with apoptotic autologous tumor cells that has potential immunostimulating and antineoplatic activities. Dendritic cells (DCs) were treated with interleukin-1beta, tumor necrosis factor alpha, interferon-alpha (IFN-a), IFN-gamma and polyinosinic:polycytidylic acid (p-I:C) to produce mature alpha type-1 polarized DCs (alphaDC1) that are capable of producing high levels of interleukin-12p70 (IL-12p70). The alphaDC1 are subsequently pulsed with apoptotic autologous tumor cells. Upon administration, these DCs are able to induce a potent cytotoxic T lymphocyte (CTL) response against tumor associated antigens (TAAs), resulting in tumor cell lysis and inhibition of tumor cell growth. Apoptotic tumor cells contain an array of TAAs.
An antibody-drug conjugate (ADC) containing a fully human monoclonal antibody (AGS-16C) directed to the ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3), conjugated via a non-cleavable linker to monomethyl auristatin F (MMAF), an auristatin derivative and a potent microtubule inhibitor, that has potential antineoplastic activity. Upon intravenous administration of ADC AGS-16C3F, the monoclonal antibody moiety of this conjugate selectively binds to ENPP3 then is internalized and undergoes proteolytic cleavage to release MMAF. MMAF binds to and inhibits tubulin polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. While normally expressed at low levels in the proximal tubules of the kidney, the type II transmembrane glycoprotein ENPP3 has been found to be overexpressed in renal neoplasms.
A radioimmunoconjugate comprised of rituximab, a recombinant chimeric monoclonal antibody directed against the CD20 antigen, and labeled with iodine I 131 with potential antineoplastic activity. The antibody moiety of iodine I 131 rituximab binds to the CD20 antigen thereby delivering cytotoxic iodine I 131 specifically to cancer cells expressing CD20. The CD20 antigen, a hydrophobic transmembrane protein, is expressed on normal pre-B and mature B lymphocytes.
A peptide vaccine containing the amino acids 267 through 274 of the human immunodeficiency virus type 1 (HIV-1) gag core protein (gag:267-274), with potential immunostimulating activity. Upon vaccination, the immune system may exert a potent cytotoxic T-lymphocyte (CTL) response against the xenoantigen gag:267-274 and produces pro-inflammatory cytokines. The concomitant administration of a cancer peptide vaccine may benefit from an already activated immune system and may augment an immune response against the administered tumor associated antigen(s). Gag:267-274 peptide is highly immunogenic and may potentially be used as a cancer immunoadjuvant.
Complete resolution of all signs and symptoms in all affected organs or tissues in chronic Graft versus Host Disease (cGVHD).
Improvement in one or more organ or tissue without progression in other affected organs or tissue in chronic Graft versus Host Disease (cGVHD).
Change towards improvement from the pretreatment baseline, but not meeting the criteria for Complete Response or Partial Response in chronic Graft versus Host Disease (cGVHD).
Improvement in some organs, but worsening in others in chronic Graft versus Host Disease (cGVHD); this is categorized as progressive disease.
Recurrence of malignancy following hematopoietic cell transplantation, based on one or more of the following parameters: marrow morphology, flow cytometry, cytogenetic studies, including fluorescence in situ hybridization, electrophoresis, immunofixation assays, and polymerase chain reaction-based assays for disease markers, or imaging results.
Damage to the phrenic nerve that is present at birth.
Withdrawal signs and symptoms that present during the postnatal period and are caused by drug use by the pregnant mother.
A bleeding disorder that is diagnosed during childhood, with the presenting symptom of excessive bleeding.
A dietary supplement containing the modified citrus pectin (MCP) derived from the soluble fiber of citrus fruit peels and a galectin-3 inhibitor with potential antioxidant, hypocholesterolemic, immunostimulatory, metal chelating, and anti-metastatic activities. MCP is a low molecular weight version of pectin composed of short, slightly-branched carbohydrate chains and is modified for enhanced absorbability. The bioactive fragments, most likely the galactan-containing portion, of pectin binds to galectin-3, a carbohydrate-binding protein involved in imflammation, heart disease and is upregulated on the surface of certain types of tumor cells. Binding of MCP may result in the suppression of cancer cell aggregation, adhesion, proliferation and metastasis. In addition, MCP decreases prostate specific antigen (PSA) levels and may remove heavy metals. Also, unsaturated oligogalacturonic acids in MCP may stimulate the immune system through the activation of natural killer cells, cytotoxic T-cells, and B-cells.
A small molecule inhibitor of histone methyltransferase with potential antineoplastic activity. Upon intravenous administration, EPZ-5676 specifically blocks the activity of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic genes. This eventually leads to an induction of apoptosis in the leukemic cells bearing the MLL gene translocations. DOT1L, a non-SET domain-containing histone methyltransferase, specifically methylates H3K79 and plays a key role in normal cell differentiation and in the development of leukemia with MLL gene rearrangement on chromosome 11 and promotes the expression of leukemia-causing genes.
Drug withdrawal symptoms in a fetus following maternal discontinuation or reduction of use of one or more addictive substance(s) that have caused fetal physiological dependence.
A disorder that affects the female or male reproductive system and is present at birth. Representative examples include ovarian agenesis, vaginal agenesis, and penile agenesis.
Damage to the phrenic nerve that was not present at birth.
Damage to the phrenic nerve that results in paralysis of the hemidiaphragm and was not present at birth.
A whole cell vaccine derived from a distinct subset of dendritic cells (DCs) with a plasma cell-like morphology that exhibits immunomodulating activity. Plasmacytoid dendritic cells (pDCs) express a characteristic set of surface markers, such as CD123 (interleukin-3 receptor alpha chain), BDCA-2 (blood dendritic cell antigen 2; CD303) and BDCA-4 (CD304), as well as intracellular toll-like receptors 7 and 9. Upon stimulation, the activated pDCs produce substantial amounts of interferon (IFN) alpha, and to a lesser degree IFN-beta, as well as other cytokines and chemokines, such as tumor necrosis factor alpha and interleukins 1, 6 and 8. In addition, these pDCs, directly or indirectly stimulate T-cells, B-cells and natural killer cells. This may potentially lead to increased immunity against tumor cells.
A synthetic 14-amino acid peptide derived from a novel human peptide hormone, Tumor-Cells Apoptosis Factor (TCApF), with potential antineoplastic activity. Upon intravenous administration, tumor-cells apoptosis factor hormone-peptide binds to the T1/ST2 receptor (IL1RL1) and activates both caspase 8 and Bcl-2 mediated apoptosis, in addition to the activation of p38 MAPK and JNK signaling cascades in tumor cells. Furthermore, this agent inhibits angiogenesis by suppressing the expressions of vascular endothelial growth factor A (VEGFA) and fms-related tyrosine kinase 1 (VEGFR1). Tumor-cells apoptosis factor hormone-peptide also modulates immune system responses via increasing the expressions of interleukin-10 and anti-angiogenic interleukin. T1/ST2 receptor, a member of the toll/interleukin-1 receptor superfamily, is overexpressed in certain cancer cells.
A proprietary 44-nucleotide L-stereoisomer RNA oligonucleotide conjugated to a 40 kDa polyethylene glycol (PEG) that targets hepcidin with potential anti-anemic activity. Upon intravenous or subcutaneous administration, PEG-linked L-RNA oligonucleotide hepcidin targeting agent NOX-H94 binds to hepcidin and prevents it from binding to the iron channel ferroportin, located on the basolateral surface of gastrointestinal enterocytes and the plasma membrane of macrophages. This prevents hepcidin-induced internalization and degradation of ferroportin, thus decreasing macrophage iron retention. In turn, binding of NOX-H94 to hepcidin normalizes plasma iron levels and increases erythropoiesis. This may inhibit anemia caused by inflammation. Hepcidin, a peptide hormone that plays a key role in the homeostasis of systemic iron, is upregulated during acute and chronic inflammation in response to cytokines. The unique mirror-image configuration of this agent renders it resistant to hydrolysis and shows a low antigenicity profile. Pegylation increases the half-life of this agent.
A radioconjugate and glutamine analog consisting of the fluorine F 18 labeled 2S, 4R stereoisomer of 4-fluoroglutamine with potential use as a metabolic tracer for tumor imaging. Upon intravenous administration, fluorine F 18 4-L-fluoroglutamine (2S,4R) is preferentially taken up by cancer cells, possibly driven by c-Myc upregulation. Upon positron emission tomography (PET), cancer cells can be imaged. Tumor cells use the amino acid glutamine for nutritional purposes necessary for energy production and growth; as tumor cells proliferate more rapidly than normal healthy cells, glutamine uptake is higher in certain cancer cells.
A fetal affliction that has a neurological basis and manifests as a developmental disability.
A proprietary tablet formulation containing an extract from Largetrifoliolious Bugbane rhizome (Shengma), the dried root of Cimicifuga sp., with potential use for relieving menopausal symptoms. The Largetrifoliolious bugbane rhizome supplement contains total saponins, including phytoestrogens that can modulate estrogen receptor signaling. This supplement is used to reduce disease symptoms, such as sweating, toothache, headache, ulcers, and insomnia. In women, this supplement may be used to reduce symptoms related to menopause.
A nutritional supplement containing probiotic cultures of Lactobacillus acidophilus (L. acidophilus), L. rhamnosus Streptococcus thermophilus, Bifidobacterium lactis, (B. lactis), B. longum and B. bifidum, with gastrointestinal (GI) protective and immunomodulating activities. Upon oral administration, the bacteria in this probiotic supplement help maintain adequate colonization of the GI tract and modulate the composition of the normal microflora. Upon colonization of the GI tract, the probiotic bacteria form a protective barrier that helps maintain the integrity of the epithelial barrier. This will interfere with the attachment of pathogenic bacteria and other harmful substances, prevent inflammation and improve GI function.
A radioconjugate comprised of the synthetic pyrimidine analogue 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine (d-FMAU) labeled with the radioisotope fluorine F 18 (18F-d-FMAU), that can potentially be used as an imaging agent upon positron emission tomography (PET). Upon administration, fluorine F 18 FMAU is distributed and taken up by cells based on the rate of the cell's DNA synthesis. Upon PET imaging, cell proliferation in tumors can be assessed as tumor cells have a higher rate of DNA synthesis than normal, healthy cells. This agent is not catabolized and has a long half-life compared to the radioconjugate carbon C 11 thymidine.
A preparation containing the nonabsorbable polymer polyethylene glycol (PEG or macrogol) 3350 and sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid with laxative activity. Upon oral administration, the PEG-3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid-based laxative promotes the retention of water in the bowel. This increases the water content of stool, which results in increased gastrointestinal motility and evacuation of colonic contents. This results in a complete cleansing of the colon. Compared to the 4 liter PEG-3350-based preparations, this PEG-based laxative is a low volume (2 liter) preparation, which improves patients' tolerance.
An opportunistic infection caused by the human papillomavirus in a patient with AIDS.
A synthetic, multivalent, lysine-rich, pseudopeptide and nucleolin antagonist with potential anti-angiogenic, antineoplastic and pro-apoptotic activities. Upon administration, IPP-204106N antagonizes nucleolin leading to a downregulation of cell-surface nucleolin; preventing the binding of certain growth promoting ligands to nucleolin may suppress tumor cell proliferation and angiogenesis. In addition, IPP-204106N is able to translocate to the nucleolus and bind to nucleolar nucleolin. This prevents nucleolin from binding to and stabilizing mRNA of the anti-apoptotic Bcl2; destabilizing Bcl2 mRNA leads to a reduction in Bcl2 protein synthesis and induces apoptosis. Further, this agent can antagonize nucleophosmin. Nucleolin, a nucleolar phosphoprotein, is overexpressed on the cell surface of certain cancer cells and binds ligands involved in cell proliferation, adhesion and angiogenesis.
A preparation containing the nonabsorbable polymer polyethylene glycol (PEG or macrogol) 3350 with laxative activity. Upon oral administration, the PEG-3350-based laxative NER1006 promotes the retention of water in the bowel. This increases both the water content and volume of stool, which results in increased gastrointestinal motility and the evacuation of colonic contents leading to a complete cleansing of the colon. Compared to the 4 liter PEG-3350-based preparations, this PEG-based laxative is a low volume (2 liter) preparation, which may improve tolerance.
A capsule containing the steroidal saponin ginsenoside Rg3 isolated from the root of Panax ginseng, with potential cancer preventive and anti-angiogenic activities. Upon oral administration, ginsenoside Rg3 appears to inhibit endothelial cell proliferation, migration and tubular formation, and promotes cancer cell apoptosis. This agent also modulates the activities of certain growth factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and matrix metalloproteinases (MMPs), on tumor angiogenesis. In addition, ginsenoside Rg3 may be able to sensitize cancer cells to some chemotherapeutic agents.
Greater than 90% reduction of primary tumor; no metastatic tumor (as above except bone); no new bone lesions, all pre-existing lesions improved on bone scan; HVA/VMA normal.
No evidence of primary tumor, no evidence of metastases (chest, abdomen, liver, bone, bone marrow, nodes, etc.), and HVA/VMA normal.
Fifty to 90% reduction of primary tumor; 50% or greater reduction in measurable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by greater than 50%.
No new lesions; less than 50% reduction but less than 25% increase in any existing lesion (exclude bone marrow evaluation).
Greater than 50% reduction of any measurable lesion (primary or metastases) with, less than 50% reduction in any other site; no new lesions; less than 25% increase in any existing lesion (exclude bone marrow evaluation).
A low-grade, well differentiated squamous cell carcinoma that arises from the penis. It is characterized by the presence of papillary architectural patterns and hyperkeratosis. It is not associated with human papillomavirus infection.
A benign neoplasm, morphologically a fibroma with osseous components.
A malignant mixed neoplasm of the liver comprising neoplastic hepatocytes and bile duct epithelial cells; both elements displaying evidence of malignancy.
A malignant neoplasm arising from the brown adipose tissue in animals, usually in the subcutis and the thoracic cavity.
An assessment of the equivocality of disease progression based on a newly identified lesion.
Not all target tumors or non-target tumors were assessed.
The most severe pain an individual can conceive of experiencing.
A fully human monoclonal antibody against killer-cell immunoglobulin-like receptors (KIR), with potential antineoplastic activity. Upon administration, lirilumab binds to KIR, thereby preventing the binding of KIR ligands to KIR on natural killer (NK) cells. By blocking these inhibitory receptors, NK cells become activated and attack cancer cells leading to tumor cell death. KIR, a member of the immunoglobulin superfamily, is expressed on the surface of NK cells.
A topical cellular cytokine solution containing a distinct combination of growth factors and cytokines secreted by and released from amnion-derived multipotent progenitor (AMP) cells, with potential immunomodulating and skin healing activities. The amnion-derived cellular cytokine solution (ACCS) contains near physiological levels of transforming growth factor beta, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, as well as the angiogenesis factors platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and angiogenin that are normally found in healing wounds. Upon spraying the solution onto affected areas, the cytokines and growth factors in ACCS appear to increase the migration, proliferation and differentiation of both keratinocytes and fibroblasts; enhance the migration and phagocytosis of macrophages in wounds; and increase epithelialization. Together these processes may accelerate skin healing and tissue repair. Also, ACCS may be beneficial in the treatment of radiation burns of the skin.
An injectable form of a polysaccharide isolated from the radix of Astragalus membranaceus (PG2), used in traditional Chinese medicine, with potential hematopoiesis inducing and immunomodulating activities. Upon injection, APS may be able to relieve certain chemotherapy-induced side effects, including myelosuppression, fatigue, mucositis, pain, nausea and vomiting, as well as loss of appetite and body weight. Also, APS may exert immunostimulatory activities by stimulating B-lymphocytes, activating T-lymphocytes, inducing cytokine production, and activating macrophages and natural killer cells through as of yet unidentified mechanism(s). APS may improve compliance of radiotherapy and/or chemotherapy.
A cancer vaccine containing immunogenic, HLA-A2-specific epitopes derived from X-box-binding protein 1-unspliced (XBP1-US), XBP1-spliced (SP), syndecan-1 (CD138), and CS1 (CD2 subset 1, CRACC, SLAMF7, CD319) with potential immunomodulating and antineoplastic activities. Upon subcutaneous administration, XBP1-US/XBP1-SP/CD138/CS1 multipeptide vaccine PVX-410 may stimulate the immune system to induce a cytotoxic T-lymphocyte response against the four myeloma-specific antigens. The tumor associated antigens (TAAs) XBP1-US, XBP1-SP, CD138 and CS1, are overexpressed on the surface of multiple myeloma (MM) cells.
An orally available, monovalent mimetic of second mitochondrial-derived activator of caspases (Smac/DIABLO) and inhibitor of IAPs (Inhibitor of Apoptosis Proteins) with potential antineoplastic activity. Smac mimetic GDC-0917 binds to the Smac binding groove on IAPs, including the direct caspase inhibitor X chromosome-linked IAP (XIAP) and the cellular IAPs 1 and 2. This inhibits the activities of these IAPs and promotes the induction of apoptosis through apoptotic signaling pathways. IAPs are overexpressed by many cancer cell types and suppress apoptosis by binding to and inhibiting active caspases-3, -7 and -9 via their baculoviral lAP repeat (BIR) domains.
A recombinant T-cell engaging bispecific monoclonal antibody (BiTE) directed against human prostate specific membrane antigen (PSMA) and the CD3 epsilon subunit of the T cell receptor complex, with potential immunostimulating and antineoplastic activities. Anti-PSMA/CD3 BiTE monoclonal antibody MT112 possesses two antigen-recognition sites, one for PSMA, and one for the CD3 complex, a group of T cell surface glycoproteins that complex with the T cell receptor (TCR). This bispecific monoclonal antibody brings PSMA-expressing tumor cells and cytotoxic T lymphocytes (CTLs) together, which may result in the CTL-mediated cell death of PSMA-expressing cells. PSMA, a tumor associated antigen, is overexpressed on the surface of metastatic and hormone-refractory prostate cancer cells.
A calixarene-based compound and galectin-1 (Gal-1) inhibitor with potential anti-angiogenic and antineoplastic activities. Upon subcutaneous administration, galectin-1 inhibitor OTX008 binds Gal-1 which leads to Gal-1 oxidation and proteosomal degradation, through an as of yet not fully elucidated mechanism, and eventually downregulation of Gal-1. This decreases tumor cell growth and inhibits angiogenesis. Gal-1, a multifunctional carbohydrate-binding protein, is often overexpressed on tumor cells and plays a key role in cancer cell proliferation, apoptosis, tumor angiogenesis and evasion of immune responses.
A recombinant chaperone-peptide complex-based vaccine composed of a complex between heat shock protein hsp110 and the human melanoma-associated antigen gp100, with potential antineoplastic activity. Upon vaccination, recombinant hsp110-gp100 chaperone complex activates the immune system to exert a cytotoxic T cell immune response and antigen-specific interferon-gamma production against gp100-overexpressing cancer cells. Gp100, is overexpressed in a variety of cancer cell types. Hsp110, binds to and chaperones full-length proteins during heat shock; as an immunoadjuvant it is able to enhance an immune response against antigen(s) and stimulate T-lymphocyte activation.
A library of items for patient self-reporting of symptoms and side effects associated with cancer treatment trials.
A long-acting, recombinant analog of the endogenous human granulocyte colony-stimulating factor (G-CSF) with hematopoietic activity. Similar to G-CSF, long-acting G-CSF analog SPI-2012 binds to and activates specific cell surface receptors and stimulates neutrophil progenitor proliferation and differentiation, as well as selected neutrophil functions. Therefore, this agent may decrease the duration and incidence of chemotherapy-induced neutropenia. The long-acting G-CSF analog SPI-2012 extends the half-life of G-CSF, allowing for administration once every 3 weeks.
A 9 amino acid-based cyclic, tumor specific homing, arginine-glycine-aspartic acid (RGD)-based peptide (CRGDKRGPDC), with tumor penetrating activity. The iRGD contains the RGD motif as well as the C-terminal end binding (CendR) motif that increases internalization. Upon administration, the RGD motif of the iRGD peptide is able to specifically target tumors by binding to alphavbeta3/alphavbeta5 integrins on tumor endothelium. In turn, iRGD is cleaved by specific tumor proteases, which exposes the positively charged CendR motif. This motif binds to neuropilin-1 (NRP-1), a receptor overexpressed on certain tumor cells. This increases vascular permeability of tumor blood vessels and promotes tumor penetration. Compared to other RGD peptides, this agent is able to both improve delivery and increase the accumulation of co-administered or conjugated chemotherapeutic agents in the tumor.
A human monoclonal antibody directed against the human epidermal growth factor receptor ErbB3 (Her3) with potential antineoplastic activity. Anti-ErbB3 receptor monoclonal antibody REGN1400 binds to ErbB3 and prevents neuregulin 1 ligand binding to ErbB3, which may result in an inhibition of ErbB3-dependent phosphatidylinositol-3 kinase (PI3K)/Akt signaling. This eventually leads to the inhibition of cellular proliferation and differentiation. ErbB3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in a variety of solid tumors and its overexpression generally correlates with poor prognosis and tumor resistance.
An orally bioavailable inhibitor of the class I phosphoinositide 3-kinase (PI3K) alpha and beta isoforms with potential antineoplastic activity. PI3K alpha/beta inhibitor BAY1082439 selectively inhibits both PI3K alpha, including mutated forms of PIK3CA, and PI3K beta in the PI3K/Akt/mTOR pathway, which may result in tumor cell apoptosis and growth inhibition in PI3K-expressing and/or PTEN-driven tumor cells. By specifically targeting class I PI3K alpha and beta, this agent may be more efficacious and less toxic than pan PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is frequently found in solid tumors and results in increased tumor cell growth, survival, and resistance to chemotherapy and radiotherapy. PIK3CA, one of the most highly mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K. PTEN, a tumor suppressor protein and negative regulator of PI3K activity, is often mutated in a variety of cancer cells.
An allogeneic cancer vaccine composed of a mixture of lethally irradiated whole melanoma cancer cells obtained from four different melanoma cell lines, with potential immunostimulating and antineoplastic activities. Upon intradermal injections, allogeneic irradiated melanoma cell vaccine may stimulate the body's immune system to exert a cytotoxic T-lymphocyte response and antibody-dependent cellular cytotoxicity (ADCC) against the melanoma cancer cells.
A bispecific monoclonal antibody directed against the human epidermal growth factor receptor ErbB3 (Her3) and the human insulin-like growth factor-1 receptor (IGF-1R), with potential antineoplastic activity. The anti-IGF-1R targeting arm of anti-IGF-1R/anti-ErbB3 bispecific monoclonal antibody MM-141 binds to IGF-1R on tumor cells thereby preventing the binding of the natural ligands IGF-1, 2 and heregulin (HRG) to IGF-1R; the anti-ErbB3 therapeutic arm prevents the binding of neuregulin (NRG) to ErbB3. This prevents the activation of the PI3K/AKT signal transduction pathway and may result in both the induction of apoptosis and a decrease in cellular proliferation in IGF-1R and ErbB3-overexpressing tumor cells. IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily, and ErB3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, are frequently overexpressed in solid tumors.
A radiolabeled divalent histamine-succinyl-glycine (HSG) hapten-peptide linked with the macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the radionuclide gallium (Ga) 68 with potential use in diagnostic imaging. After pretargeting with a bispecific monoclonal antibody (BiMoAB) directed against both a tumor associated antigen (TAA) and the HSG hapten-peptide, the HSG portion of administered gallium Ga 68-labeled di-HSG-DOTA peptide IMP-288 binds the anti-HSG portion of the BiMoAB; Ga-68 radioisotopic activity localized to tumor cells bearing the TAA can then be visualized upon positron emission tomography (PET).
A plasma-derived, polyclonal, intravenous immunoglobulin formulation (IVIG) containing standardized high levels of antibodies against respiratory syncytial virus (RSV), a single-stranded, enveloped paramyxovirus, with potential immunomodulating activity. The high-titer RSV immune globulin RI-001 is derived from healthy donors with high amounts of RSV antibodies. Upon intravenous administration, the antibodies against RSV may provide passive immunization against RSV. This may prevent lower respiratory tract infections by RSV in immunocompromised patients. The polyclonal antibodies in RI-001 are able to target various viral epitopes.
A finding indicating that an excess amount of norepinephrine is secreted by a tumor.
A finding indicating that an excess amount of normetanephrine is secreted by a tumor.
A finding indicating that an excess amount of epinephrine is secreted by a tumor.
A finding indicating that an excess amount of metanephrine is secreted by a tumor.
A finding indicating that an excess amount of dopamine is secreted by a tumor.
A finding indicating that an excess amount of methoxytyramine is secreted by a tumor.
A topical formulation of the hydrochloride salt of the tropane alkaloid cocaine, with local anesthetic activity. Upon topical application of the cocaine hydrochloride solution to nasal mucous membranes, cocaine reversibly binds to and blocks the voltage-gated sodium channels in the neuronal cell membranes. By stabilizing neuronal membranes, cocaine inhibits the initiation and conduction of nerve impulses and produces a reversible loss of sensation.
A biosimilar of pegfilgrastim, a long-acting pegylated form of recombinant human granulocyte colony-stimulating factor (G-CSF) filgrastim, with hematopoietic activity. In a similar manner to G-CSF, pegfilgrastim biosimilar LA-EP2006 binds to and activates specific cell surface receptors, stimulating neutrophil progenitor proliferation and differentiation and selected neutrophil functions. Therefore, this agent may prevent the incidence and shorten the duration of chemotherapy-induced neutropenia. Conjugation of the cytokine with a branched polyethylene glycol molecule significantly increases this agent's therapeutic half-life compared to filgrastim.
A radiopharmaceutical agent comprised of a pegylated arginine-glycine-aspartic acid (RGD) dimer (PRGD2) labeled with technetium Tc 99m, with potential alphaVbeta3 integrin imaging activity when used with single photon emission computed tomography (SPECT). After intravenous administration of technetium Tc 99m-3PRGD2, the RGD moiety binds to alphaVbeta3 integrin on the cell membrane via the cyclic RGD motif. Upon PET imaging, alphaVbeta3 integrin-expressing tumor cells can be visualized and expression levels can be quantified. Compared to other radiolabeled RGD-containing peptides, this agent shows an increased affinity for alphaVbeta3 integrin, enhanced tumor uptake as well as improved pharmacokinetics. AlphaVbeta3 integrin, a member of the integrin receptor family, is overexpressed on certain tumor cells and tumor endothelial cells while minimally or not expressed on healthy, normal cells; this receptor plays a key role in angiogenesis, tumor proliferation and survival.
A radioimmunoconjugate containing a glycoengineered, humanized monoclonal antibody directed against the human epidermal growth factor receptor HER3 (ErbB3) and labeled with the radioisotope zirconium Zr 89, with radioisotopic activity and potential use as an imaging agent as well as potential antineoplastic activity. Upon administration, the RO5479599 moiety of zirconium Zn 89-labeled RO5479599 binds to the extracellular domain of HER3 and inhibits HER3 dimerization, thereby preventing EGFR-dependent signaling. In addition, RO5479599 elicits enhanced antibody-dependent cellular cytotoxicity (ADCC). Upon binding, the radioisotope moiety may be detected using positron emission tomography (PET), thereby allowing the imaging and quantification of HER3-expressing tumor cells. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors; it has no active kinase domain but is activated through heterodimerization with other members of the EGFR receptor family, such as HER2.
A morphologic finding indicating the presence of less than or equal to twenty five percent of clear or vacuolated cells that resemble the normal zona fasciculata in adrenocortical tumors.
A finding about one or more characteristics of adrenal cancer, following the rules of the ENSAT staging v7 classification system.
A pathologic finding about one or more characteristics of adrenal cancer, following the rules of the ENSAT staging v7 classification system.
A pathologic finding about one or more characteristics of adrenal cancer, following the rules of the ENSAT staging v7 classification system as they pertain to staging of the primary tumor.
Adrenal cancer with tumor size equal or less than 5.0 cm. There is no invasion of tissues outside the adrenal gland. (7th Ed, 2009)
Adrenal cancer with tumor size more than 5.0 cm. There is no invasion of tissues outside the adrenal gland. (7th Ed, 2009)
Adrenal cancer with tumor of any size. There is invasion of the fat that surrounds the adrenal gland. (7th Ed, 2009)
Adrenal cancer with tumor of any size. There is invasion of nearby organs such as the kidney, pancreas, spleen or liver. (7th Ed, 2009)
A pathologic finding about one or more characteristics of adrenal cancer, following the rules of the ENSAT staging v7 classification system as they pertain to staging of the lymph nodes.
Adrenal cancer with no involvement of regional lymph nodes. (7th Ed, 2009)
Adrenal cancer with involvement of regional lymph nodes. (7th Ed, 2009)
A clinical finding about one or more characteristics of adrenal cancer, following the rules of the ENSAT staging v7 classification system.
A clinical finding about one or more characteristics of adrenal cancer, following the rules of the ENSAT staging v7 classification system as they pertain to distant metastases.
Adrenal cancer with no involvement of distant organs or tissues. (7th Ed, 2009)
Adrenal cancer with involvement of distant organs or tissues such as liver, bone or brain. (7th Ed, 2009)
A term that refers to the staging of adrenal cortical carcinoma according to the European Network for the Study of Adrenal Tumors (ENSAT).
Stage I includes: T1, N0, M0. Tumor 5 cm or less in greatest dimension. The tumor has not invaded the surrounding tissues or organs and has not spread to lymph nodes or distant organs or tissues. (ENSAT 7th Ed, 2009)
Stage II includes: T2, N0, M0. Tumor greater than 5 cm. The tumor has not invaded surrounding tissues or organs and has not spread to lymph nodes or distant organs or tissues. (ENSAT 7th Ed, 2009)
Stage III includes: T3/T4, N0/N1, M0. Tumor of any size that has spread to the fat outside the adrenal gland or into nearby organs or tissues and/or has spread to the regional lymph nodes. (ENSAT 7th Ed, 2009)
Stage IV includes: Any T, Any N, M1. Tumor of any size that involves distant organs such as liver, bone or brain. The tumor may or may not involve nearby organs, tissues or lymph nodes. (ENSAT 7th Ed, 2009)
An orally available inhibitor of extracellular signal-regulated kinase (ERK), with potential antineoplastic activity. Upon oral administration, MK-8353 inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways; thereby, preventing ERK-dependent tumor cell proliferation and survival. The mitogen-activated protein kinase (MAPK)/ERK pathway is often upregulated in a variety of tumor cell types and plays a role in tumor cell proliferation, differentiation and survival.
A proprietary oral formulation composed of the poorly soluble, synthetic triazole agent, itraconazole, dispersed in a polymer matrix, with antifungal and potential anti-angiogenic activities. Upon oral administration, itraconazole inhibits the enzyme cytochrome P450 lanosterol 14 alpha-demethylase, resulting in a decrease in fungal ergosterol synthesis. Although the exact mechanism through which itraconazole inhibits angiogenesis has yet to be fully elucidated, this agent appears to inhibit the Hedgehog (Hh) signaling pathway, cholesterol synthesis and mammalian target of rapamycin (mTOR) signaling in endothelial cells. This agent may also prevent the activation of and signaling by various angiogenic growth factors. By decreasing the tumor vasculature and nutrient supply, itraconazole ultimately inhibits tumor cell growth. The solid dispersion of itraconazole in the polymer matrix enhances dissolution of itraconazole in the gastrointestinal tract and increases its bioavailability; this allows for the administration of a much lower dose compared to itraconazole alone.
An orally available 21-substituted-19-nor-progestin and selective progesterone receptor modulator (SPRM), with potential anti-progesterone and antineoplastic activities. Upon oral administration, telapristone competitively binds to the progesterone receptor (PR) in progesterone-responsive tissue and inhibits PR-mediated gene expression. This interferes with progesterone activity in the reproductive system. As a result, this agent may suppress ovulation and inhibit proliferation of endometrial tissue. Also, this agent may prevent cell growth and induce apoptosis in estrogen receptor (ER) and PR-positive breast cancer cells through a reduction in progesterone levels, ER downregulation and a suppression of the expression of cyclin-dependent kinases (CDK) 2 and 4, ultimately leading to G1/S cell cycle arrest. Unlike some other SPRMs, this agent does not exert any estrogenic, androgenic, anti-estrogenic, and anti-androgenic activities.
An immunoconjugate containing a glycoengineered, humanized monoclonal antibody directed against the human epidermal growth factor receptor HER3 (ErbB3), with potential antineoplastic activity. Upon administration, RO5479599 binds to the extracellular domain of HER3 and inhibits HER3 dimerization; thereby, preventing EGFR-dependent signaling. In addition, RO5479599 stimulates the immune system to exert antibody-dependent cellular cytotoxicity (ADCC). This may decrease proliferation of HER3-overexpressing tumor cells. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors; it has no active kinase domain but is activated through heterodimerization with other members of the EGFR receptor family, such as HER2.
A proprietary topical formulation. Upon subcutaneous administration, the active ingredient in AK 3012 may inhibit actinic keratosis.
An injectable, nutritional lipid emulsion composed of 10% fish oil and high amounts of the fish oil-derived polyunsaturated omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Additionally, the fish oil/glycerol/egg lecithin-based emulsion contains, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, octadecatetraenoic acid, eicosaenoic acid, arachidonic acid, docosaenoic acid, and docosapentaenoic acid. This agent supplies essential fatty acids that can be incorporated into cell membranes. The fatty acids may decrease the production of certain pro-inflammatory cytokines, including interleukin 1 (IL-1), IL-6 and tumor necrosis factor (TNF). In addition to fish oil, this lipid emulsion contains egg phospholipids to maintain membrane integrity; glycerol to provide energy through glycolysis; and the antioxidant alpha-tocopherol (vitamin E).
An orally bioavailable HDM2 (human homolog of double minute 2) antagonist with potential antineoplastic activity. Upon oral administration, p53/HDM2 interaction inhibitor CGM097 inhibits the binding of the HDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this HDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited, which may result in the restoration of p53 signaling and, thus, the p53-mediated induction of tumor cell apoptosis. HDM2, a zinc finger nuclear phosphoprotein, is a negative regulator of the p53 pathway, often overexpressed in cancer cells and has been implicated in cancer cell proliferation and survival.
An orally bioavailable inhibitor of phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), activin receptor-like kinase 1 (ALK-1) and DNA-dependent protein kinase (DNA-PK), with potential anti-angiogenic and antineoplastic activities. Upon oral administration, PI3K/mTOR/ALK-1/DNA-PK inhibitor P7170 inhibits the activity of all four kinases. This prevents PI3K/mTOR and ALK-1-mediated signaling pathways and may lead to the inhibition of cancer cell growth in PI3K/mTOR-overexpressing tumor cells and angiogenesis in ALK-1-overexpressing endothelial cells. Also, by inhibiting DNA-PK, this agent inhibits the ability of tumor cells to repair damaged DNA. The PI3K/mTOR pathway is upregulated in a variety of tumors and plays an important role in regulating cancer cell proliferation, growth, and survival. ALK-1, a member of the transforming growth factor beta (TGF-b) type I receptor family, is overexpressed on endothelial cells in a variety of tumor types and increases endothelial cell proliferation and migration. DNA-PK is activated upon DNA damage and plays a key role in repairing double-stranded DNA breaks.
A microscopic finding indicating that a tumor exhibits more than one line of histologic differentiation.
A substance that inhibits protein geranylgeranyltransferase type 1 (GGTase-I), with potential antineoplastic activity. GGTase-I is involved in the posttranslational modification of a number of oncogenic GTPases, including K-Ras, N-Ras, RhoA, RhoC, Cdc42, RalA, RalB and Rac1. Inhibition of the prenylation of these oncogenic proteins inhibits both their oncogenic activity and membrane localization. This may result in cell cycle arrest and apoptosis. Protein geranylgeranylation, catayzed by GGTase-I, plays a critical role in malignant transformation and cancer cell proliferation, migration and invasion.
An autologous cancer vaccine composed of lethally irradiated leukemia cells that are genetically modified to secrete the immunostimulatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Upon intradermal injection, the autologous GM-CSF-secreting lethally irradiated leukemia cell vaccine secretes GM-CSF. In turn, GM-CSF may stimulate the immune system to attack tumor cells by enhancing the activation of dendritic cells (DCs) and promoting antigen presentation to both B- and T-lymphocytes. In addition, GM-CSF promotes antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function.
A molecular genetic abnormality indicating the presence of a mutation in exon 11 of the KIT gene located within 4q11-q12.
A molecular genetic abnormality indicating the presence of a mutation in exon 9 of the KIT gene located within 4q11-q12.
A molecular genetic abnormality indicating the presence of a mutation in exon 13 of the KIT gene located within 4q11-q12.
A radioconjugate composed of the cytokine interleukin-2 (IL-2) conjugated to the bifunctional chelating agent succinimidyl-6-hydrazinopyridine-3-carboxylate (HYNIC-NHS) and co-ligand tricine and labeled with the radioisotope technetium Tc 99m (99mTc-HYNIC-IL2), that can potentially be used as a diagnostic agent to detect tumor inflammation. Upon intravenous administration, IL-2 selectively binds to the IL-2 receptor (IL-2R) expressed on tumor infiltrating lymphocytes (TILs); upon internalization, the Tc99m moiety can be visualized using radioimaging, which allows the quantification of TILs expressing IL-2R. This agent detects tumor enlargement due to invasion by TILs and not tumor progression.
A synthetic peptide vaccine consisting of a HLA-A24-restricted human Wilms' Tumor protein-1 (WT1) peptide comprised of amino acids 235 through 243, a MHC class I-restricted peptide, with potential immunomodulating and antitumor activities. Vaccination with WT1 235-243 peptide may induce a WT1-specific cytotoxic T-lymphocyte (CTL) response against WT1 expressing cells, resulting in cell lysis and inhibition of cancer cell proliferation. WT1, a zinc finger DNA-binding protein, is overexpressed in most types of leukemia and in a variety of solid cancers.
A synthetic peptide vaccine consisting of a HLA-DRw53-restricted human Wilms' Tumor protein-1 (WT1) peptide comprised of amino acids 247 through 261, a HLA class II-restricted WT1 peptide, with potential immunomodulating and antitumor activities. Vaccination with WT1 247-261 peptide may stimulate a CD4-positive helper T-lymphocyte-mediated immune response against WT1 expressing cells. Activated helper T-cells stimulate dendritic cells, and activate the proliferation of other T-lymphoctes and B-lymphocytes. This causes tumor cell lysis and inhibition of cancer cell proliferation in WT1-overexpressing tumor cells. WT1, a zinc finger DNA-binding protein, is overexpressed in most types of leukemia and in a variety of solid cancers.
A synthetic peptide vaccine consisting of a HLA-DR15-restricted human Wilms' Tumor protein-1 (WT1) peptide comprised of amino acids 124 through 138, a HLA class II-restricted WT1 peptide, with potential immunomodulating and antitumor activities. Vaccination with WT1 124-138 peptide may stimulate a CD4-positive helper T-lymphocyte-mediated immune response against WT1 expressing cells. Activated helper T-cells stimulate dendritic cells, and activate the proliferation of other T-lymphoctes and B-lymphocytes. This causes tumor cell lysis and inhibition of cancer cell proliferation in WT1-overexpressing tumor cells. WT1, a zinc finger DNA-binding protein, is overexpressed in most types of leukemia and in a variety of solid cancers.
A non-replicating recombinant adenovirus type 5 (Ad5)-vector encoding the gene for interferon alpha-2b (IFN alpha-2b) and the gene transfer enhancement agent Syn 3, with potential antineoplastic activity. Upon intravesical administration, recombinant adenovirus-interferon with Syn3 transfects both cancerous and normal bladder cells, and the adenovirus secretes interferon (IFN alpha-2b) into the bladder. IFN exerts a direct antitumor killing effect and a bystander effect, thereby killing adjacent, non-transfected cancerous bladder cells. Syn 3 enhances the ability of the adenoviral vector to transfect cells.
An orally available cancer cell stemness kinase inhibitor with potential antineoplastic activity. Even though the exact target has not been fully elucidated, BBI503 targets and inhibits one or more pathways involved in cancer stem cell survival. As a result, cancer stem cell (CSC) growth as well as heterogeneous cancer cell growth is inhibited. CSCs, self-replicating cells able to differentiate into heterogeneous cancer cells, appear to be responsible for both tumor relapse and metastasis.
An orally bioavailable inhibitor of the insulin-like growth factor 1 receptor (IGF-1R) with potential antineoplastic activity. IGF-1R inhibitor PL225B selectively binds to and inhibits the activities of IGF-1R, which may result in both the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis in IGF-1R-overexpressing tumor cells. IGF-1R, a receptor tyrosine kinase overexpressed in a variety of human cancers, plays a significant role in the stimulation of cellular proliferation, oncogenic transformation, and suppression of apoptosis.
A synthetic, peptide cancer vaccine directed against the human telomerase reverse transcriptase catalytic subunit (hTERT) with potential immunomodulating activity. Vaccination with the UV1 telomerase peptide may stimulate cytotoxic T-cells to recognize and kill telomerase-expressing cells. Telomerase, a reverse transcriptase normally repressed in healthy cells, is overexpressed in most cancer cells and plays a key role in cellular proliferation.
A formulation containing an androgen receptor (AR) antagonist with potential antineoplastic activity. AR antagonist ODM-201 binds to ARs in target tissues; subsequently, inhibiting androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot translocate to the nucleus. This prevents binding to and transcription of AR-responsive genes that regulate prostate cancer cell proliferation. This ultimately leads to an inhibition of growth in AR-expressing prostate cancer cells.
Problems with the RF wireless technology characteristics and performance (e.g., frequency, output power, range, reception), wireless quality of service, wireless coexistence, security of wireless signals and data, and electromagnetic compatibility.
A cathepsin-activatable fluorescent probe with imaging activity. The cathepsin-activatable fluorescent probe LUM015 contains the Cy5 fluorophore linked, via a pan-cathepsin protease cleavable peptide, to a fluorescent quencher. Upon injection, the peptide in LUM015 can be cleaved by cathepsins overexpressed by tumor cells, which releases the quencher and activates the fluorophore. Upon imaging, tumor cells expressing cathepsin family proteases can be detected.
A juice extracted from watercress containing high amounts of phenethyl isothiocyanate (PEITC), with potential chemopreventive and antitumor activities. Although the mechanism(s) of action through which PEITC exerts its effect(s) has yet to be fully elucidated, PEITC is able to induce apoptosis in tumor cells through the induction of reactive oxygen species (ROS). Additionally, PEITC is able to modulate extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase (MAPK) signal transduction pathways, activating the expression of stress-responsive genes and eventually inducing apoptosis. PEITC also inhibits the expression of genes involved in tumor progression such as HIF, STAT-3, HER2, BCL-XL, and XIAP and induces the expression of genes involved in tumor suppression such as p53, ATF-2, and p57. Furthermore, this agent has been shown to reactivate the gene expression of certain detoxification enzymes.
An orally available inhibitor of monocarboxylate transporter 1 (MCT1), with potential antineoplastic activity. Upon oral administration, MCT1 inhibitor AZD3965 binds to MCT1 and prevents the transport of lactate into and out of the cell. This leads to an accumulation of lactate, intracellular acidification, and eventually cancer cell death. MCT1, a protein overexpressed on tumor cells, is responsible for the transport of monocarboxylates across the cell membrane and plays a key role in cell metabolism.
A rapidly growing serous adenocarcinoma that arises from the ovary. It is characterized by the presence of high grade cytologic features and frequent mitotic figures.
A slow-growing serous adenocarcinoma that arises from the ovary. It usually originates from borderline neoplastic processes or adenofibromas. It is characterized by the presence of low grade cytologic features and infrequent mitotic figures.
A radiopharmaceutical composed of the nonspecific perfusion agent ethylglyoxal bis(thiosemicarbazone) (ETS) linked to the beta-emitting, radioisotope copper Cu 62, with potential tumor imaging activity upon positron emitting tomography (PET). Upon injection, copper Cu 62-ETS distributes to various organs, especially the kidneys and the myocardium. Upon PET imaging, tumor blood flow can be visualized and the efficacy of antineoplastic and anti-angiogenic chemotherapeutics can be assessed. Cu62-ETS has a short half life of 9.74 minutes. ETS has an enhanced hyperemic response compared to other perfusion agents.
An epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon intravenous infusion, ABT-414 inhibits the activity of EGFR, thereby preventing EGFR-mediated signaling. This may inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase overexpressed in certain tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
An orally available nanoparticle-based formulation containing the hydrochloride salt form of gemcitabine, a broad-spectrum antimetabolite and deoxycytidine analogue, with antineoplastic activity. The formulation consists of an oil-in-water emulsion in which gemicitabine is solubilized in the excipient matrix containing a mixture of oil and (co)surfactants. Upon oral administration, gemcitabine is converted into the active metabolites difluorodeoxycytidine diphosphate (dFdCDP) and difluorodeoxycytidine triphosphate (dFdCTP) by deoxycytidine kinase. dFdCTP competes with deoxycytidine triphosphate (dCTP) and is incorporated into DNA, resulting in premature termination of DNA replication and the induction of apoptosis. Further, dFdCDP inhibits ribonucleotide reductase and reduces the deoxynucleotide pool available for DNA synthesis. Compared to gemcitabine alone, the emulsion allows for increased oral bioavailability and decreases its susceptibility to deamination and deactivation by cytidine deaminase.
An orally available inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with antineoplastic activity. Upon administration, ALK inhibitor RO5424802 binds to and inhibits ALK kinase, which leads to a disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. ALK dysregulation and gene rearrangements are associated with a series of tumors. Additionally, ALK mutations are associated with acquired resistance to small molecule tyrosine kinase inhibitors.
An herbal remedy containing Astragalus membranaceus, Panax ginseng, Atractylodes chinensis Koidz, Cimicifuga foetida, A. macrocephala Koidz, Alisma orientale Juzep, and Citrus reticulata Blanco, with potential immunomodulating, anti-oxidant and anticachexia activities. Upon oral consumption, the ingredients in this herbal supplement may modulate the activity of the immune system through a decrease in both the expression of nuclear factor-kappa B (NF-kappa B) and the production of pro-inflammatory cytokines such as interleukin-1beta (Il-1b), IL-6, and tumor necrosis factor-alpha (TNF-alpha). Increased levels of pro-inflammatory cytokines are correlated with decreased appetite and weight loss; thus, this herbal remedy may improve immune function, appetite and weight gain, which could prevent cachexia.
A human plasma-derived, polyclonal, intravenous immunoglobulin G (IgG) formulation containing high levels of antibodies against hepatitis C virus (HCV), a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family, with potential immunomodulating and antiviral activities. The hepatitis C IgG is isolated from donors expressing high amounts of HCV antibodies. Upon intravenous administration, the anti-HCV antibodies bind to the virus and provide passive immunization against HCV. This may prevent both infection by HCV in immunocompromised patients and hepatitis C-related liver disease. The polyclonal anti-HCV antibodies are able to target various viral epitopes.
A non-neoplastic abnormality that affects the placenta. Representative examples include multi-lobed and bilobed placenta.
An electrocardiographic finding of pathologic Q waves in leads V3 through V6, which is suggestive of myocardial infarction of the anterolateral wall of the left ventricle. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V1 through V4, which is suggestive of myocardial infarction of the anteroseptal wall of the left ventricle. (CDISC)
An electrocardiographic finding in leads V1 or V2 of an initial R wave duration greater than or equal to 40 ms, R wave greater than S wave, and upright T wave, which is suggestive of myocardial infarction of the posterior wall of the left ventricle. Evidence of inferior or lateral myocardial infarction is usually also present. (CDISC)
An electrocardiographic finding of pathologic Q waves in leads V5, V6, I and aVL, which is suggestive of myocardial infarction of the lateral wall of the left ventricle. (CDISC)
An electrocardiographic finding of an injury in leads corresponding to the anatomic region of the posteroinferior wall of the heart.
An electrocardiographic finding of an injury in leads corresponding to the anatomic region of the apex of the heart.
A morphologic finding indicating the presence of myxoid changes in a tissue sample.
A benign mesonephric neoplasm that arises from the uterine ligament and occurs in women with von Hippel-Lindau disease. It is a cystic lesion characterized by the presence of multiple papillary excrescences.
A rare sarcoma that arises from the cervix. This category includes low grade endometrioid stromal sarcoma and undifferentiated endocervical sarcoma.
A very rare sarcoma that arises from the cervix and is characterized by the presence of cells that resemble endometrial stromal cells.
A rare sarcoma that arises from the vagina. This category includes low grade endometrioid stromal sarcoma and undifferentiated vaginal sarcoma.
An infiltrating sarcoma that arises from the vagina. It is characterized by the presence of cells that resemble endometrial stromal cells.
A header term that includes the following breast carcinoma subtypes determined by gene expression profiling: luminal A breast carcinoma, luminal B breast carcinoma, HER2 positive breast carcinoma, basal-like breast carcinoma, triple-negative breast carcinoma, and normal breast-like subtype of breast carcinoma.
A biologic subset of breast carcinoma defined by high expression of genes characteristic of luminal epithelial cells, including estrogen receptor (ER), estrogen regulated protein LIV-1, and the transcription factors hepatocyte nuclear factor 3, HNF3A, XBP1, and GATA 3. This subtype of breast cancer is associated with a good prognosis.
A biologic subset of breast carcinoma defined by low to moderate expression of genes characteristic of luminal epithelial cells including estrogen receptor (ER), and high expression of GGH, LAPTM4B, and CCNE1. This subtype of breast cancer is associated with a good prognosis, although not as favorable as the luminal A subtype.
A biologic subset of breast carcinoma defined by high expression of genes characteristic of basal epithelial cells, including KRT5 and KRT17, annexin 8, CX3CL1, and TRIM29, and usually by lack of expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is the most common subtype of breast cancer associated with BRCA1 mutations, and is associated with a poor prognosis.
A small molecule with potential antineoplastic and antiangiogenic activities. Daporinad binds to and inhibits nicotinamide phosphoribosyltransferase (NMPRTase), inhibiting the biosynthesis of nicotinamide adenine dinucleotide (NAD+) from niacinamide (vitamin B3), which may deplete energy reserves in metabolically active tumor cells and induce tumor cell apoptosis. In addition, this agent may inhibit tumor cell production of vascular endothelial growth factor (VEGF), resulting in the inhibition of tumor angiogenesis. The coenzyme NAD+ plays an essential role in cellular redox reactions, including the redox reaction linking the citric acid cycle and oxidative phosphorylation.
An orally bioavailable selective MEK inhibitor with potential antineoplastic activity. Refametinib specifically inhibits mitogen-activated protein kinase kinase 1 (MAP2K1 or MAPK/ERK kinase 1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK, a dual specificity threonine/tyrosine kinase, is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.
A recombinant bispecific monoclonal antibody directed against both CD3 and epithelial cell adhesion molecule (EpCAM) with potential immunomodulating and antineoplastic activities. Solitomab attaches to both CD3-expressing T lymphocytes and EpCAM-expressing tumor cells, thereby selectively cross-linking tumor and T lymphocytes; this may result in the recruitment of cytotoxic T lymphocytes (CTL) to T lymphocyte/tumor cell aggregates and the CTL-mediated death of EpCAM-expressing tumor cells. CD3 is an antigen expressed on mature T cells; EpCAM, a cell surface protein, is expressed by a variety of tumor cells and is frequently found in head and neck cancers.
An orally bioavailable, second-generation, hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. HDAC inhibitor JNJ-26481585 inhibits HDAC leading to an accumulation of highly acetylated histones, which may result in an induction of chromatin remodeling; inhibition of the transcription of tumor suppressor genes; inhibition of tumor cell division; and the induction of tumor cell apoptosis. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins. Compared to some first generation HDAC inhibitors, JNJ-26481585 may induce superior HSP70 upregulation and bcl-2 downregulation.
A tricyclic indole poly(ADP-Ribose) polymerase (PARP1) inhibitor with potential chemosensitizing, radiosensitizing, and antineoplastic activities. Rucaparib selectively binds to PARP1 and inhibits PARP1-mediated DNA repair, thereby enhancing the accumulation of DNA strand breaks and promoting genomic instability and apoptosis. This may enhance the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapy and radiation therapy. PARP1 catalyzes post-translational ADP-ribosylation of nuclear proteins and is activated by single-strand DNA (ssDNA) breaks.
A specific population of autologous, pluripotent bone marrow derived cells that express high levels of the cytosolic enzyme aldehyde dehydrogenase (ALDH) with potential protective and neuro-cognition improving activity. Expression of high levels of ALDH is an indicator of the biological activity in heterogenous early stage stem cells. Upon intravenous administration, these ALDH bright cells may protect normal cells and may repair damaged cells. These cells may also protect brain cells from damage and may improve neurocognition.
A racemic mixture of the enantiomers of a synthetic alpha-lipoic lipoic acid analogue with potential chemopreventive and antineoplastic activities. Although the exact mechanism of action is unknown, 6,8-Bis(benzylthio)octanoic acid has been shown to inhibit metabolic and regulatory processes required for cell growth in solid tumors. Both enantiomers in the racemic mixture exhibit antineoplastic activity.
A boron-containing small molecule antifungal agent with broad-spectrum activity against filamentous fungi, including both mold and yeast. 5-Fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole inhibits fungal cytoplasmic leucyl-tRNA synthetase by preventing catalytic turnover, thus inhibiting synthesis of leucyl-tRNA(Leu) and consequentially blocking protein synthesis.
An inhibitor of the cell cycle checkpoint kinase 2 (chk2) with potential chemopotentiating activity. Rabusertib binds to and inhibits the activity of chk2, which may prevent the repair of DNA caused by DNA-damaging agents, thus potentiating the antitumor efficacies of various chemotherapeutic agents. Chk2, an ATP-dependent serine-threonine kinase, is a key component in the DNA replication-monitoring checkpoint system and is activated by double-stranded breaks (DSBs); activated chk2 is overexpressed by a variety of cancer cell types.
An orally bioavailable dual kinase inhibitor of c-Met (hepatocyte growth factor receptor) and VEGFR-2 (vascular endothelial growth factor receptor-2) tyrosine kinases with potential antineoplastic activity. c-Met/VEGFR kinase inhibitor E7050 binds to and inhibits the activities of both c-Met and VEGFR-2, which may inhibit tumor cell growth and survival of tumor cells that overexpress these receptor tyrosine kinases. c-Met and VEGFR-2 are upregulated in a variety of tumor cell types and play important roles in tumor cell growth, migration and angiogenesis.
The reemergence of uterine corpus sarcoma after a period of remission.
The tosylate salt of rebastinib, an orally bioavailable small-molecule inhibitor of multiple tyrosine kinases with potential antineoplastic activity. Rebastinib binds to and inhibits the Bcr-Abl fusion oncoprotein by changing the conformation of the folded protein to disallow ligand-dependent and ligand-independent activation; in addition, this agent binds to and inhibits Src family kinases LYN, HCK and FGR and the receptor tyrosine kinases TIE-2 and VEGFR-2. Rebastinib may exhibit more potent activity against T315I Bcr-Abl gatekeeper mutant kinases than other Bcr-Abl kinase inhibitors. The TIE-2 and VEGFR-2 receptor tyrosine kinases regulate angiogenesis, respectively, while the Src family kinases Abl, LYN, and HCK Src regulate a variety of cellular responses including differentiation, division, adhesion, and the stress response.
An antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody, directed against the extracellular domain of the human CD70 molecule, conjugated to the auristatin analogue monomethyl auristatin phenylalanine (MMAF), with potential antineoplastic activity. The anti-CD70 antibody moiety of vorsetuzumab mafodotin selectively binds to the extracellular domain of CD70 on tumor cell surfaces. Upon internalization, the MMAF moiety is released, binds to tubulin and inhibits its polymerization, which may result in G2/M phase arrest, tumor cell apoptosis and inhibition of cellular proliferation in tumor cells that overexpress CD70. CD70, the ligand for the costimulatory receptor CD27 and a member of the tumor necrosis factor (TNF) family, is found on the surfaces of various types of cancer cells.
A radioconjugate consisting of an orally bioavailable small-molecule inhibitor of the epidermal growth factor receptor (erbB or HER) family of tyrosine kinases radiolabeled with carbon-14 with potential antineoplastic and beta-emitting radioisotope activity. PF-00299804 specifically and irreversibly binds to and inhibits human Her-1, Her-2, and Her-4, resulting in the proliferation inhibition and apoptosis of tumor cells that overexpress these receptors. The HER receptor family of tyrosine kinases, often overexpressed by a variety of tumor cell types, may contribute to tumor cell proliferation, differentiation, migration, and survival. PF-00299804 radiolabeled with carbon C-14 may be used as a radiotracer in pharmacological studies of PF-00299804 metabolism.
A polypeptide derived from the Salmonella filament protein flagellin with potential radioprotective and anticancer activities. As a toll-like receptor 5 (TLR5) agonist, entolimod binds to and activates TLR5 thereby stimulating tumor necrosis factor production and activating nuclear factor kappa B (NF-kB). This induces NF-kB-mediated signaling pathways and inhibits the induction of apoptosis. This may prevent apoptosis in normal, healthy cells during radiotherapy of cancerous cells and may allow for increased doses of ionizing radiation. In addition, entolimod may inhibit radiation-independent proliferation in TLR5-expressing tumor cells.
Withdrawal signs and symptoms that present during the perinatal period and are caused by drug use by the pregnant mother.
An electrocardiographic finding of an injury in leads corresponding to the anatomic region of the posterolateral wall of the heart.
An orally bioavailable inhibitor of the c-Met receptor tyrosine kinase with potential antineoplastic activity. Volitinib selectively binds to and inhibits the activation of c-Met in an ATP-competitive manner, and disrupts c-Met signal transduction pathways. This may result in cell growth inhibition in tumors that overexpress the c-Met protein. C-Met encodes the hepatocyte growth factor receptor tyrosine kinase and plays an important role in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis; this protein is overexpressed or mutated in a variety of cancers.
A biologic subset of breast carcinoma defined by high expression of many genes expressed by adipose and other non-epithelial tissues.
A sensation of discomfort or distress that worries an individual or interrupts their ability to complete desired activities.
An electrocardiographic finding of an injury in leads corresponding to the anatomic region of the subendocardial layer of the wall of the heart.
A class of quinoline compounds defined by the presence of two aromatic ring structures which are attached via a side chain to carbon 3 of the qunolinyl structure. The two aromatic moieties are typically NAPTHALENE and BENZENE. Several compounds in this class are used as ANTITUBERCULAR AGENTS.
The mesylate salt form of dabrafenib, an orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations.
A papule (circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to less than 10mm in diameter at the widest point) that exhibits increased pigmentation (is darker) compared to the surrounding skin.
The spread of a malignant neoplasm to the ovary. This may be from a primary ovarian malignant neoplasm involving the opposite ovary, or from a malignant neoplasm at a distant site.
A type of Oculocutaneous albinism with varying degrees of skin and hair hypopigmentation, numerous ocular changes and misrouting of the optic nerves at the chiasm. Cutaneous hypopigmentation is often visible at birth and signs of nystagmus and strabismus present in the first year of life. Visual changes are not progressive. Caused by mutations in the membrane-associated transporter protein (MATP) gene, SLC45A2, encoding a transporter protein which is thought to mediate melanin synthesis. Inheritance is autosomal recessive.
A nodule of the skin that exhibits an increased amount of pigmentation.
Disclosing information about oneself that is seen as a violation of social norms.
Any agent that inhibits the action of an interleukin. These agents inhibit various immune functions.
Any agent that is capable of modulating the immune system in order to exert antineoplastic effects. Antineoplastic immunomodulating agents either activate the immune system, restore certain immune system activators or abrogate immunosuppression.
A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1,PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. This results in the activation of T-cells and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and and plays a key role in in tumor evasion from host immunity.
Changes in quantitative and qualitative composition of MICROBIOTA. The changes may lead to altered host microbial interaction or homeostatic imbalance that can contribute to a disease state often with inflammation.
Compounds that inhibit or block the activity of a PHOSPHOLIPASE A2 enzyme.
Compounds that inhibit the action of HYDROXYLASES that act on PROLINE to form HYDROXYPROLINE.
Long-term changes in the electrophysiological parameters and/or anatomical structures of the HEART ATRIA that result from prolonged changes in atrial rate, often associated with ATRIAL FIBRILLATION or long periods of intense EXERCISE.
The cis isomer of clomiphene which exhibits weak estrogen agonist activity evaluated for antineoplastic activity against breast cancer. (NCI04)
A specific category of drugs that prevent sleepiness by specifically targeting sleep-mechanisms in the brain. They are used to treat DISORDERS OF EXCESSIVE SOMNOLENCE such as NARCOLEPSY. Note that this drug category does not include broadly-acting central nervous system stimulants such as AMPHETAMINES.
A screening phenotype consisting of both elevated WAIST CIRCUMFERENCE and elevated fasting TRIGLYCERIDES level.
FEVER accompanied by a significant reduction in NEUTROPHIL count associated with CHEMOTHERAPY.
Tumors or cancer of the PROSTATE which can grow in the presence of low or residual amount of androgen hormones such as TESTOSTERONE.
A delusional disorder of belief in infestation by insects or other parasites. This FORMICATION is typically accompanied by dermatological manifestation such as PRURITUS that may lead to self-mutilation in order to remove the perceived parasites. It can be either primary or secondary to a somatic or psychiatric condition.
An acute and severe skin disease with clinical and histological features of destruction and detachment of the skin epithelium and mucous membranes. Onset may occur at any age, but the risk increases after 40 years. Three subforms have been described according to the percentage of the body surface area affected: Stevens-Johnson syndrome (less than 10%), Lyell syndrome (greater than 30%) and an intermediate form (10-29%). The initial manifestations are nonspecific: a seemingly banal rash, fever, and a burning sensation involving the eyes, mouth and genitalia. The rash rapidly progresses to become vesicular and bullous on the face and body. High fever is a constant feature. Two thirds of cases are triggered by a drug allergy. In rare cases, the disease is associated with infections or bone marrow transplantation. The remaining 25-30% of cases are classed as idiopathic. The prognosis for patients with extensive forms is poor.
Unexplained neurologic condition characterized by episodes of atonic seizures, convulsions or staring spells with further cognitive decline.
An orally bioavailable selective androgen receptor modulator (SARM), with potential tissue-selective androgenic/anti-androgenic activity. Upon oral administration, LY2452473 acts as an agonist in select tissues and organs, including skeletal muscle, bone and the penis, thereby binding to and activating androgen receptor (AR) while acting as an antagonist in the prostate, thereby blocking AR activation and AR-mediated cellular proliferation. This may improve muscle mass and strength, bone formation, and erectile dysfunction while not stimulating growth of the prostate.
A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity.
A fusion protein complex composed of a mutated form of the cytokine interleukin (IL)-15 (IL-15N72D) and a soluble, dimeric IL-15 receptor alpha (IL-15Ra) Fc fusion protein (IL-15Ra-Fc) (IL-15N72D/IL-15Ra-Fc), with potential antineoplastic activity. Upon administration, superagonist interleukin-15:interleukin-15 receptor alphaSu/Fc fusion complex ALT-803 binds to the IL-2/IL-15 receptor beta-common gamma chain (IL-2Rbetagamma) receptor on natural killer (NK) and CD8+ T lymphocytes, which activates and increases the levels of NK cells and memory CD8+(CD44high) T-cells. The memory T-cells enhance the secretion of the cytokine interferon-gamma (IFN-g), which further potentiates the immune response against tumor cells. This may increase tumor cell killing and decrease tumor cell proliferation. IL-15 regulates CD8+ T and NK cell development, activation and proliferation. By coupling IL-15 to IL15Ra-Fc, this agent has a prolonged drug half-life and shows an increased ability to bind IL-2Rbetagamma, which enhances its immune stimulatory activity as compared to IL-15 alone.
An extended-release (ER) formulation composed of irinotecan, which is a semisynthetic derivative of camptothecin and a topoisomerase I-inhibitor prodrug, that is conjugated, via a proprietary biodegradable ester-based linker, to polyethylene glycol (PEG), with antineoplastic activity. Upon administration of etirinotecan pegol (EP), the agent penetrates into the leaky tumor vasculature and accumulates in the tumor. The linker slowly hydrolyzes and releases irinotecan, which leads to sustained exposure of the tumor to irinotecan. In turn, irinotecan is converted to the biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN38) by a carboxylesterase. SN38 inhibits topoisomerase I activity by stabilizing the cleavable complex of topoisomerase I and DNA; this results in DNA breaks that inhibit DNA replication and trigger apoptosis. Pegylation provides improved systemic exposure, increases drug penetration into tumors and decreases drug clearance, thereby increasing the duration of therapeutic effects while lowering the toxicity profile.
An orally bioavailable, 3-amidinophenylalanine-derived, second generation serine protease inhibitor prodrug targeting the human urokinase plasminogen activator (uPA) system with potential antineoplastic and antimetastatic activities. After oral administration, upamostat is converted to the active N alpha-(2,4,6-triisopropylphenylsulfonyl)-3-amidino-(L)-phenylalanine-4-ethoxycarbonylpiperazide (WX-UK1), which inhibits several serine proteases, particularly uPA; inhibition of uPA may result in the inhibition of tumor growth and metastasis. uPA is a serine protease involved in degradation of the extracellular matrix and tumor cell migration and proliferation.
An orally bioavailable pyrrolopyridine derivative and Smoothened (Smo) antagonist with potential antineoplastic activity. Smo antagonist TAK-441 selectively binds to and inhibits the activity Smo, which is a cell surface co-receptor for ligands in the Hedgehog (Hh) family. This may result in a suppression of Hh-mediated signaling pathways, thereby inhibiting the growth of tumor cells in which this pathway is aberrantly activated. Smo is a G-protein coupled receptor that lies just downstream of the Hh cell surface receptor Patched-1 in the Hh pathway; in the absence of ligand, Patched-1 (Ptch1) inhibits Smo, and ligand binding to Ptch1 results in increased levels of Smo. The Hh-mediated signaling pathways play an important role in cellular growth and differentiation, and tissue repair; constitutive activation of this pathway is associated with uncontrolled cellular proliferation in a variety of cancers.
An orally bioavailable, adenosine triphospate mimetic, and inhibitor of Aurora kinases, vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptor (PDGFRs), with potential antineoplastic activity. Upon administration, ilorasertib selectively binds to and inhibits Aurora kinases A, B and C, which may disrupt both the assembly of the mitotic spindle apparatus and chromosome segregation, and inhibit both cellular division and proliferation in Aurora kinase-overexpressing tumor cells. In addition, ilorasertib selectively binds to and inhibits VEGFRs and PDGFRs, which may result in the inhibition of both angiogenesis and tumor cell proliferation in VEGFR/PDGFR-overexpressing tumor cells. This agent also inhibits the Src family of cytoplasmic tyrosine kinases. Aurora kinases A, B and C, are serine/threonine kinases that play essential roles in mitotic checkpoint control and are overexpressed by a wide variety of tumor cell types. Both VEGFRs and PDGFRs are receptor tyrosine kinase families whose members may be upregulated in various tumor cell types.
An angiopoietin (Ang) 1 and 2 neutralizing peptibody, with potential antiangiogenic activity. AMG 386 targets and binds to Ang1 and Ang2, thereby preventing the interaction of the angiopoietins with their target tie2 receptors. This may inhibit angiogenesis and may eventually lead to an inhibition of tumor cell proliferation.
An orally bioavailable small molecule, with potential hematopoiesis inducing and antiviral activities. Upon oral administration, myelo001 stimulates the differentiation of bone marrow cells of the leukocytic, lymphocytic, and erythrocytic lineages, and prevents apoptosis of hematopoietic cells. This prevents chemotherapy-induced neutropenia (CIN), inhibits the risk of infections, increases tolerance and allows for the continuation of the neutropenia-inducing chemotherapeutic agent. In addition, myelo 001 has antiviral properties.
An orally bioavailable inhibitor of c-Met, with potential antineoplastic activity. Upon administration, c-Met inhibitor MK8033 binds to and inhibits the autophosphorylation of the c-Met protein, which disrupts c-Met signal transduction pathways and may induce cell death in tumor cells overexpressing or expressing constitutively activated c-Met protein. In addition, MK8033 inhibits Ron (receptor originated from nantes, MST1R). c-Met protein, which is encoded by the proto-oncogene MET, is a receptor tyrosine kinase also known as hepatocyte growth factor receptor (HGFR); this protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis. Ron, a member of the Met family of cell surface receptor tyrosine kinases, is also overexpressed on certain tumor cell types.
An orally bioavailable imidazopyridazine and inhibitor of Janus kinase 2 mutant V617F (JAK2V617F), with potential antineoplastic activity. Upon oral administration, gandotinib selectively and competitively inhibits the activation of JAK2V617F, which may result in the inhibition of the JAK-STAT signaling pathway and the induction of apoptosis in JAK2V617F-expressing tumor cells. JAK2V617F has a substitution of phenylalanine for valine at amino acid position 617 and plays a key role in tumor cell proliferation and survival.
An orally bioavailable N-hydroxyacrylamide-derived inhibitor of both human pan-histone deacetylase (HDAC) enzymes and the serine/threonine protein kinase Akt (protein kinase B), with potential antineoplastic activity. Upon administration, HDAC inhibitor MPT0E028 selectively binds to and inhibits HDACs, which inhibits deacetylation of histone proteins and leads to the accumulation of highly acetylated histones. This may result in both an induction of chromatin remodeling, and the selective transcription of tumor suppressor genes. This prevents cell division and induces both cell cycle arrest and apoptosis, which may inhibit the proliferation of susceptible tumor cells. In addition, MPT0E028 inhibits the phosphorylation and activation of Akt, which prevents the activation of downstream signaling pathways, independent of its HDAC inhibitory activity. HDACs, upregulated in many tumor cell types, are a family of enzymes that deacetylate histone proteins. Akt, overexpressed in many tumor cell types, plays a key role in tumor cell proliferation and survival.
A piperazine derivative that acts as a serotonin reuptake inhibitor, as a 5-HT3 receptor antagonist, and 5-HT1A receptor agonist. It is used for the treatment of anxiety and depression.
An inhibitor of histone deacetylase (HDAC) enzymes, with potential antineoplastic activity. Upon administration, OBP-801 inhibits the activity of HDACs; this results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to selective transcription of tumor suppressor genes, tumor suppressor protein-mediated inhibition of tumor cell division and induction of tumor cell apoptosis. This may inhibit proliferation of susceptible tumor cells. HDAC, which is upregulated in many tumor cell types, deacetylates chromatin histone proteins.
Severe mucocutaneous reactions; skin detachment of 10 to 30 percent of body surface area most commonly triggered by medications, characterised by extensive necrosis and detachment of the epidermis.
A structurally abnormal heart condition, without symptoms of heart failure, that confers a high risk of progression to symptomatic heart failure.
Itching sensation referred to a site distant from the stimulation site.
The disposition to develop an allergic or pseudoallergic reaction.
A pathological nonimmune process generally directed towards a foreign substance, which results in tissue injury, which is usually transient. It is the realization of the pseudoallergic disposition. A variety of mechanisms such as direct histamine release, complement activation, cyclooxygenase activation and bradykinin generation may be involved.
The disposition to develop a pseudoallergic reaction, the pseudoallergic reaction itself or its consequences.
A type of non-immune hypersensitivity process that represents the underlying mechanism of pseudoallergic conditions.
The disposition to develop a pseudoallergic reaction.
A condition that confers a high risk of progression to actual heart failure but lacks actual structural or functional disorder of the heart.
Acceptance of treatment; cautious behavior at times; willingness to comply with the dentist, at times with reservation, but patient follows the dentist's directions cooperatively.
Refusal of treatment, forceful crying, fearfulness, or any other overt evidence of extreme negativism.
Reluctance to accept treatment, uncooperative, some evidence of negative attitude but not pronounced (sullen, withdrawn).
Good rapport with the dentist, interest in the dental procedures, laughter and enjoyment.
A process characterised by an initial humoral or cell-mediated immune response to a foreign antigen resulting in the production of specific antibodies and/or immune cells which may then lead to an allergic disposition.
Migraine triggered by an allergic inflammatory process.
A condition in which the ability to see is impaired.
A type of hypothyroidism that results from a defect in thyroid-stimulating hormone secretion.
Excessive or inappropriate LACTATION in females or males, and not necessarily related to PREGNANCY. Galactorrhea can occur either unilaterally or bilaterally, and be profuse or sparse. Its most common cause is HYPERPROLACTINEMIA.
Cardiovascular disease resulting from arteriosclerosis.
A squamous cell carcinoma that arises from the nasopharynx and is characterized by prominent production of keratin.
A malignant neoplasm arising from the great vessels.
A steroidal aldosterone antagonist with potassium-sparing diuretic activity. Prorenoate antagonizes the activity of aldosterone at the mineralocorticoid receptor in the nephron and thereby prevents sodium reabsorption. This interferes with the sodium/potassium exchanger and causes sodium and water excretion while reducing potassium excretion.
Partial or total inability to hear sounds in both ears.
Patients with SSOAD exhibit a broad phenotypic spectrum involving short stature associated with advanced bone maturation and early-onset osteoarthritis (OA), as well as mild dysmorphic features consisting of midface hypoplasia, brachydactyly, broad great toes, and lumbar lordosis. Other features include intervertebral disc disease and osteochondritis dissecans, which is characterized by separation of articular cartilage and subchondral bone from the articular surface. Phenotypes are highly variable even among patients within the same family, and there are no apparent genotype-phenotype correlations (Dateki et al., 2017). The term 'dissecans' comes from 'dis' meaning 'from' and 'secare' meaning 'cut off,' and is not to be confused with 'desiccans' derived from 'desiccare' meaning to 'dry up.' Dissecans refers to the appearance of part of the bone having been cut away.
A low grade epithelial tumor arising from the ovary. It is characterized by an atypical proliferation of epithelial cells. There is no evidence of stromal invasion.
A heart or vascular abnormality which is inborn or present at birth.
A type of plant that is native to southern Africa and has white, pink, purple, or red flowers and 3- to 5-lobed leaves. An essential oil that smells like roses is taken from the leaves and used in perfume, in mosquito repellants, and in aromatherapy to treat skin problems and to reduce stress. The scientific name is Pelargonium graveolens.
A nevus characterised by the presence of excessive pigment.
Benign epidermal proliferations or tumors; some are viral in origin.
Asymptomatic separation of the uterine wall, usually at the site of a prior uterine scar, that does not include the overlying serosa.
A decreased amount of enamel mineralization.
Congenital reticular ichthyosiform erythroderma (CRIE), also known as ichthyosis with confetti (IWC), is a rare skin condition characterized by slowly enlarging islands of normal skin surrounded by erythematous ichthyotic patches in a reticulated pattern. The condition starts in infancy as a lamellar ichthyosis, with small islands of normal skin resembling confetti appearing in late childhood and at puberty. Histopathologic findings include band-like parakeratosis, psoriasiform acanthosis, and vacuolization of keratinocytes with binucleated cells in the upper epidermis, sometimes associated with amyloid deposition in the dermis. Ultrastructural abnormalities include perinuclear shells formed from a network of fine filaments in the upper epidermis (summary by Krunic et al., 2003).
A morphologic variant of dermatofibrosarcoma protuberans characterized by the presence of a fibrosarcomatous component.
A type of shock characterized by inadequate cardiac preload due to obstructed venous return (e.g. pericardial tamponade, tension pneumothorax, abdominal compartment) or obstruction of arterial blood flow (e.g. pulmonary embolism).
Reluctance or refusal of a child to be breastfed or eat, manifested as gagging, vomiting, turning head away from food, or avoidance of sensation in or around the mouth (i.e. toothbrushing or face-washing).
A hydrobromide salt form of vortioxetine, a serotonin (5-HT) modulator and stimulator (SMS), with antidepressant activity. Vortioxetine inhibits the reuptake of serotonin and norepinephrine from the synaptic cleft and acts variably as a serotonin receptor agonist (5-HT1A), partial agonist (5-HT1B) or antagonist (5-HT3, 5-HT1D and 5-HT7). It is not clear how this agent's purported multimodal mechanism of action contributes to its antidepressant effect; however, it is presumed to increase the synaptic availability of serotonin and norepinephrine.
A combination preparation of conjugated estrogens and the selective estrogen receptor modulator (SERM) bazedoxifene that can be used for hormone replacement purposes. The conjugated estrogens increase the diminishing levels of estrogen in menopausal and postmenopausal women by binding to and activating estrogen receptors (ERs), which, in turn, bind to estrogen response elements (EREs) in target genes; this results in the transcription of estrogen-regulated genes. Maintaining adequate estrogen levels decreases symptoms such as hot flashes, night sweats, irregular menstruation, fat redistribution, mood swings, sleep disorders, vaginal dryness and osteoporosis. Bazedoxifene specifically binds to and activates ERs in certain tissues, including liver, bone, breast, and endometrium, and also promotes the transcription of estrogen-regulated genes in these tissues. However, bazedoxifene acts as an estrogen antagonist in uterine and breast tissue, thereby blocking the proliferative effects of estrogen-binding to ER-positive cells in these tissues.
Decreased or absent activity of the enzyme 11-beta-hydroxylase caused by loss-of-function mutations in the CYP11B1 gene, resulting in congenital adrenal hyperplasia. Clinical manifestations of this condition include virilization in 46XX infants and hypertension.
Deficiency of 5-alpha-reductase type 2 in genital tissues resulting in reduced local concentration of dihydrotestosterone (DHT).
Endogenous factors and drugs that inhibit or block the activity of FACTOR XA.
A form of hyperkeratosis characterized by thickening of the cornified layer without retained nuclei.
Excessive formation of fibrous bands of scar tissue in between muscle fibers.
A nonparallel arrangement of cardiac myocytes.
Urolithiasis in which the composition of the stones is predominantly cystine.
The presence of calcium- and phosphate-containing calculi (stones) in the kidneys.
An increased concentration of sodium(1+) in the urine.
An anomalous build up of copper (Cu) in the liver.
Hyperplasia of the biliary tree, as manifested by increased size of bile ducts, dilated lumen, and histologically by an increased number of epithelial cells or hyperplasia.
A finding of an empty space in a histological section of paraffin-embedded tissue created by the dissolution of cholesterol crystals.
Hyperplasia of the biliary tree, as manifested by increased size of bile ducts, dilated lumen, and histologically by an increased number of epithelial cells or hyperplasia. [HPO:probinson]
An accumulation of microglial cells in nervous tissue as a result of injury.
An inflammatory infiltrate composed exclusively or predominantly of eosinophils.
Increased width of the uvula (subjective finding).
Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive, but rarely metastasizing tumor of the deep dermis and subcutaneous tissue. It typically presents during early or middle adult life and is most frequently located on the trunk and proximal extremities (Sandberg et al., 2003).
A viral disorder characterized by SARS (Severe Acute Respiratory Syndrome)-like symptoms caused by MERS-CoV (MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS).
A subtype of Charcot-Marie-Tooth type 4 with characteristics of childhood onset of slowly progressing, demyelinating sensorimotor neuropathy, focally folded myelin sheaths in nerve biopsy, reduced nerve conduction velocities and the typical Charcot-Marie-Tooth phenotype (i.e. distal muscle weakness and atrophy, and sensory loss). There is evidence this disease is caused by homozygous or compound heterozygous mutation in the SBF1 gene on chromosome 22q.
A form of oculocutaneous albinism with characteristics of skin and hair hypopigmentation, nystagmus and iris transillumination. The prevalence is unknown. It has been discovered in several Faroese families and one patient of Lithuanian origin. Patients have a light skin pigmentation that is reported as lighter than their relatives. Caused by mutation in the C10orf11 gene (10q22.3) encoding a 198 amino acid protein. Currently, little is known about the biological function of this gene in humans and its role in this disease pathogenesis.
A type of oculocutaneous albinism recently discovered in one Chinese family, with characteristics of light hair at birth that darkens with age, white skin, transparent irides, photophobia, nystagmus, foveal hypoplasia and reduced visual acuity. Caused by mutations in the SLC24A5 gene (15q21.1).
A type of oculocutaneous albinism found in one Pakistani family to date, with characteristics of white skin, golden hair, photophobia, nystagmus, foveal hypoplasia and impaired visual acuity. Affects males and females equally. Mapped to a locus on chromosome 4q24 but the gene has not yet been discovered.
A yellowish to pinkish colored, synthetic leaflet material. p-Chloro-o-toluidine is used in industry in the manufacture of azo dyes and is used in the production of the pesticide chlordimeform. This substance is a possible mutagen and is reasonably anticipated to be a human carcinogen that may be associated with an increased risk of bladder cancer. (NCI05)
A group of five inherited disorders caused by mutations in the AUH, DNAJC19, OPA3, and TAZ genes. The disorders are characterized by impairment in the function of mitochondria, resulting in the accumulation and excretion of 3-methylglutaconic acid, and the presence of 3-methylglutaric acid in the urine.
Where a significant amount of gingival tissue can be seen as a person smiles.
Severe life-threatening illness resulting from infection, usually meningitis or sepsis, in an individual lacking a spleen, whether congenital asplenia or post-splenectomy.
Occurs where the relationship between the teeth of a normal jaw and a complete denture (or between two complete dentures) is not harmonious.
Enlargement of the parotid gland due to air insufflation.
A difference in the height of the marginal edges of adjacent teeth.
Making vocal utterances that are distressing sounding and socially inappropriate due to their intensity, frequency, duration and/or setting, as a manifestation of some form of brain disease, usually dementia.
An artificial connection from artery to vein that can sustain three consecutive two-needle cannulations with no infiltrations at the prescribed needle gauge and blood flow rate.
Decreased vertical distance from the vermilion border of the lower lip to the inferior-most point of the chin.
A microdeletion at 16p11.2, characterized by a predisposition to obesity, developmental delay and autism spectrum disorders.
An inherited syndrome of skeletal and retinal malformations with early blindness as well as cataracts and retinal detachment.
Caries in which the lesion has removed so much of the crown that its original site of initiation cannot be determined with any certainty.
A rare benign pseudocyst that extends into the submandibular space and is associated with mucus extravasation that can occur spontaneously or as the result of trauma or obstruction to the salivary gland excretory duct and spillage of mucin into the surrounding soft tissues.
Characterized by upper and lower incisors that have emerged forward making the teeth and lips protrude.
Spinal myoclonus is generally due to a tumor, infection, injury, or degenerative process of the spinal cord, and is characterized by involuntary rhythmic muscle contractions, usually at a rate of more than one per second. Myoclonus occurs synchronously in several muscles and can be increased in severity and frequency by fatigue or stress, but is usually unaffected by sensory stimuli. Spinal myoclonus ceases during sleep or anesthesia.
Death resulting from previously existing disease or a disease developing during pregnancy which was not associated with gestation, but which was aggravated by the unique physiologic changes of pregnancy. Examples of indirect deaths include those associated with epilepsy, diabetes, cardiac disease and hormone-dependent malignancies.
An inflammatory necrotizing lesion occurring in minor salivary glands.
A common taste disorder where there is a lingering, often unpleasant taste despite the absence of any stimulus to initiate the distorted taste.
Mixture of fat and blood in a joint cavity following trauma.
A disorder that affects the myocardial ion channels, altering the electrical properties of the heart and changing the ECG and/or predisposing the subject to pro-arrhythmic events.
Bleeding into the tissue of the brain not due to a significant external force. Despite the word ""cerebral"" this includes all regions of brain tissue, not merely telencephalon.
A disorder in which there is abnormal electrical activity in the heart associated with a genetic disorder.
Superficial chemical burn or reaction to the detergent or flavoring compounds associated with use of certain brands of toothpastes.
Presence of inflammation in the soft tissue surrounding a dental implant without signs of any loss of supporting bone
Thickening or cording of lymphatic tissues following axillary node biopsy or dissection.
Rapidly developing osteoporosis characterized primarily by bone marrow edema of a self-limiting nature.
Present when both the upper and lower jaws are posterior to the normal limits of the face.
A pegylated form of naloxone, a peripherally-acting mu-opioid receptor antagonist, that can be used to reduce opioid-induced symptoms. Upon administration, naloxegol binds to and blocks mu-opioid receptors in the peripheral nervous system. This prevents peripheral opioid receptor activation and abrogates opioid-induced side effects, such as opioid-induced constipation (OIC). Pegylation of naloxone reduces permeability across the blood-brain barrier (BBB) and prevents this agent from interfering with the analgesic activity of opioid receptor agonists.
A potent and selective inhibitor of both phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR kinase inhibitor VS-5584 inhibits mTOR kinase and all class I PI3K isoforms. Consequently, this disrupts phosphorylation of substrates downstream of PI3K and mTOR and may result in apoptosis and growth inhibition in susceptible tumor cells. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy. mTOR is a serine/threonine kinase downstream of PI3K, which also has PI3K-independent activity. Consequently, this agent may potentially be more potent than an agent that inhibits either PI3K kinase or mTOR kinase.
A form of hereditary spastic paraplegia with onset usually in adulthood of progressive bilateral lower limb weakness and spasticity, sphincter dysfunction, decreased vibratory sense at the ankles and with additional manifestations including optical neuropathy, nystagmus, strabismus, decreased hearing, scoliosis, pes cavus, motor and sensory neuropathy, amyotrophy, blepharoptosis and ophthalmoplegia.
An autosomal dominant condition caused by mutation(s) in the SPAST gene, encoding spastin. It is characterized by progressive lower extremity spasticity and weakness.
A chromosomal disorder with distinctive clinical findings characterised by early central hypotonia, developmental delay and intellectual deficit, epilepsy, and autistic behaviour. Facial dysmorphism is absent or subtle and major malformations are rare. The syndrome is usually sporadic and not inherited and results from an abnormal extra chromosome in each cell containing mirror-image segments of genetic material. The isodicentric chromosome is made up of two extra copies of a segment of genetic material from chromosome 15, which is attached end-to-end. Typically this copied genetic material includes a region of the chromosome called 15q11-q13.
CSF1R-related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is characterized by executive dysfunction, memory decline, personality changes, motor impairments, and seizures. A frontal lobe syndrome (e.g., loss of judgment, lack of social inhibitors, lack of insight, and motor persistence) usually appears early in the disease course. The mean age of onset is usually in the fourth decade. Affected individuals eventually become bedridden with spasticity and rigidity. The disease course ranges from two to 30 or more years (mean: 8 years).
Autosomal recessive primary microcephaly (MCPH) is a rare genetically heterogeneous disorder of neurogenic brain development with features of reduced head circumference at birth with no gross anomalies of brain architecture and variable degrees of intellectual impairment. It is more common in specific populations, e.g. northern Pakistanis. Consanguinity appears to play a role in incidence. Patients have a reduction in head circumference at birth of at least 2 standard deviations below ethnically matched, age- and sex-related mean values. Caused by mutations in MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, STIL, CEP63, CEP135 , CASC5 and PHC1. These mutations appear to lead to reduced generation of cerebral cortical neurons during embryonic neurogenesis. Inheritance is autosomal recessive.
9q22.3 microdeletion is a chromosomal change in which a small piece of chromosome 9 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome in a region designated q22.3. This chromosomal change is associated with delayed development, intellectual disability, certain physical abnormalities, and the characteristic features of a genetic condition called Gorlin syndrome.Many individuals with a 9q22.3 microdeletion have delayed development, particularly affecting the development of motor skills such as sitting, standing, and walking. In some people, the delays are temporary and improve in childhood. More severely affected individuals have permanent developmental disabilities along with intellectual impairment and learning problems. Rarely, seizures have been reported in people with a 9q22.3 microdeletion.About 20 percent of people with a 9q22.3 microdeletion experience overgrowth (macrosomia), which results in increased height and weight compared to unaffected peers. The macrosomia often begins before birth and continues into childhood. Other physical changes that are sometimes associated with a 9q22.3 microdeletion include the premature fusion of certain bones in the skull (metopic craniosynostosis) and a buildup of fluid in the brain (hydrocephalus). Affected individuals can also have distinctive facial features such as a prominent forehead with vertical skin creases, upward- or downward-slanting eyes, a short nose, and a long space between the nose and upper lip (philtrum).9q22.3 microdeletions also cause the characteristic features of Gorlin syndrome (also known as nevoid basal cell carcinoma syndrome). This genetic condition affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors. In people with Gorlin syndrome, the type of cancer diagnosed most often is basal cell carcinoma, which is the most common form of skin cancer. Most people with this condition also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors, which can cause facial swelling and tooth displacement. Other types of tumors that occur in some people with Gorlin syndrome include a form of childhood brain cancer called a medulloblastoma and a type of benign tumor called a fibroma that occurs in the heart or in a woman's ovaries. Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull.
Isolated deficiency of long-chain 3-hydroxyl-CoA dehydrogenase (LCHAD) is an autosomal recessive disorder characterized by early-onset cardiomyopathy, hypoglycemia, neuropathy, and pigmentary retinopathy, and sudden death (IJlst et al., 1996).
An orally available selective androgen receptor (AR) downregulator (SARD), with potential antineoplastic activity. Upon oral administration, AZD3514 binds to the AR ligand binding domain and inhibits the binding of androgen, thereby preventing androgen-dependent AR signaling. AZD3514 also causes downregulation of AR expression, which further prevents AR-mediated signaling. This results in an inhibition of proliferation in AR-overexpressing tumor cells. AR plays a key role in the proliferation of castration-resistant prostate cancer cells.
An orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Ipatasertib binds to and inhibits the activity of Akt in a non-ATP-competitive manner, which may result in the inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
A thiazolylamide and helicase-primase enzyme inhibitor that is active against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). Pritelivir inhibits the helicase-primase complex and prevents helicase or primase catalytic cycling of viral DNA, which interferes with DNA replication and growth. This agent does not require activation by HSV thymidine kinase and has a longer plasma half-life than nucleoside analogues.
A calcimimetic and calcium-sensing receptor (CaSR) agonist composed of a synthetic peptide comprised of seven D-amino acids that can be used to treat secondary hyperparathyroidism (sHPT) in hemodialysis patients with chronic kidney disease (CKD). Upon intravenous administration, etelcalcetide mimics calcium and allosterically binds to and activates the CaSR expressed by the parathyroid gland. This suppresses the synthesis and secretion of parathyroid hormone (PTH), thereby reducing PTH levels and lowering serum calcium and phosphorus levels. Elevated PTH is often observed in patients with CKD and is associated with dysregulated calcium-phosphate homeostasis.
An inhibitor of glycogen synthase kinase-3 (GSK-3), with potential antineoplastic activity. Upon administration, LY2090314 binds to and inhibits GSK-3 in an ATP-competitive manner. This prevents GSK-3-mediated phosphorylation of beta-catenin, which inhibits the subsequent ubiquitination and proteosomal degradation of beta-catenin. This leads to the activation of the Wnt/beta-catenin pathway and the induction of apoptosis in susceptible tumor cells. GSK-3, a serine/threonine kinase, plays a key role in numerous pathways involved in protein synthesis, cellular proliferation, differentiation, and apoptosis. The Wnt/beta-catenin signaling pathway plays key roles in both cellular proliferation and differentiation. The increased expression of beta-catenin, a transcriptional activator, correlates with decreased cellular proliferation and improved prognosis in select cancers.
Inadequate intake of protein and/or energy over a prolonged period of time resulting in loss of fat and/or muscle stores due to chronic disease.
Inadequate intake of protein and/or energy over a prolonged period of time resulting in loss of fat and/or muscle stores due to acute disease or injury.
Inadequate intake of protein and/or energy over a prolonged period of time resulting in loss of fat and/or muscle stores due to starvation.
Oral food/beverage intake that is inconsistent with reference standard intake for type, variety, or quality. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Higher intake of one or more minerals compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Lower intake of one or more minerals compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Higher intake of one or more vitamins compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of one or more vitamins compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of copper compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Higher intake of phosphorus compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Weight gain more than that which is desired or planned. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of cobalt compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of boron compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of molybdenum compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of chromium compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of manganese compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of selenium compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of iodine compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of fluoride compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of sulfate compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of magnesium compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of chloride compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of sodium compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of cobalt compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of boron compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of molybdenum compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of chromium compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of manganese compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of selenium compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of iodine compared to established reference standards or recommendations based on physiological needs(Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of copper compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of fluoride compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of sulfate compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of sodium compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of phosphorus compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of magnesium compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of chloride compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of biotin compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of pantothenic acid compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of vitamin B12 compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of vitamin B6 compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of biotin than compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of pantothenic acid than compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of vitamin B12 than compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of vitamin B6 than compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of soy protein compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of psyllium compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of plant sterol ester compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of plant stanol ester compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of non-nutritive food additives compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of caffeine compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of b-glucan compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of soy protein compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of psyllium compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of plant sterol ester compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of plant stanol ester compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of beta glucan compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Higher intake of bioactive substances compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Lower intake of bioactive substances compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Actual or observed intake of bioactive substances, including single or multiple functional food components, ingredients, dietary supplements, alcohol. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Parenteral infusion that provides more calories/kcal/kJ or nutrients compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Enteral infusion that provides more calories/kcal/kJ or nutrients compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Parenteral infusion that provides fewer calories/kcal/kJ or nutrients compared to established reference standards or recommendations based on physiological needs. (Source: Academy of Nutrition and Dietetics Nutrition Informatics Committee 2013)
Enteral infusion that provides fewer calories/kcal/kJ or nutrients compared to established reference standards or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3)
Energy intake that exceeds energy expenditure, established reference standards, or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Future energy intake that is anticipated, based on observation, experience, or scientific reason, to be less than estimated energy expenditure, established reference standards, or recommendations based on physiological needs. (Source: Academy of Nutrition and Dietetics Nutrition Informatics Committee 2013).
Future energy intake that is anticipated, based on observation, experience, or scientific reason, to be less than estimated energy expenditure, established reference standards, or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Energy intake that is less than energy expenditure, established reference standards, or recommendations based on physiological needs. (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Rate of growth or growth velocity greater than expected, or weight gain that is higher in comparison with goal or reference standard (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Rate of growth or growth velocity slower than expected, or weight gain that is suboptimal in comparison with goal or reference standard (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Decreased need for a specific nutrient compared to established reference standards or recommendations based on physiological needs (Source: International Dietetics and Nutrition Terminology (IDNT) Reference Manual, edition 4; ISBN #978-0-88091-467-3).
Coughing, wheezing, or shortness of breath that is triggered by allergens, infection, or other irritants.
Localized loss of skin pigmentation, often in patches.
Meckel syndrome, also known as Meckel-Gruber syndrome, is a severe pleiotropic autosomal recessive developmental disorder caused by dysfunction of primary cilia during early embryogenesis. There is extensive clinical variability and controversy as to the minimum diagnostic criteria. Early reports, including that of Opitz and Howe (1969) and Wright et al. (1994), stated that the classic triad of Meckel syndrome comprises (1) cystic renal disease; (2) a central nervous system malformation, most commonly occipital encephalocele; and (3) polydactyly, most often postaxial. However, based on a study of 67 patients, Salonen (1984) concluded that the minimum diagnostic criteria are (1) cystic renal disease; (2) CNS malformation, and (3) hepatic abnormalities, including portal fibrosis or ductal proliferation. In a review of Meckel syndrome, Logan et al. (2011) stated that the classic triad first described by Meckel (1822) included occipital encephalocele, cystic kidneys, and fibrotic changes to the liver. Genetic Heterogeneity of Meckel Syndrome See also MKS2 (603194), caused by mutation in the TMEM216 gene (613277) on chromosome 11q12; MKS3 (607361), caused by mutation in the TMEM67 gene (609884) on chromosome 8q; MKS4 (611134), caused by mutation in the CEP290 gene (610142) on chromosome 12q; MKS5 (611561), caused by mutation in the RPGRIP1L gene (610937) on chromosome 16q12; MKS6 (612284), caused by mutation in the CC2D2A gene (612013) on chromosome 4p15; MKS7 (267010), caused by mutation in the NPHP3 (608002) gene on chromosome 3q22; MKS8 (613885), caused by mutation in the TCTN2 gene (613846) on chromosome 12q24; MKS9 (614209), caused by mutation in the B9D1 gene (614144) on chromosome 17p11; MKS10 (614175), caused by mutation in the B9D2 gene (611951) on chromosome 19q13; MKS11 (615397), caused by mutation in the TMEM231 gene (614949) on chromosome 16q23; MKS12 (616258), caused by mutation in the KIF14 gene (611279) on chromosome 1q32; and MKS13 (617562), caused by mutation in the TMEM107 gene (616183) on chromosome 17p13.
Any condition related to a disturbance between proper intake and utilization of nourishment.
The invasion of an organism's body tissues by disease-causing agents and their multiplication, as well as the reaction by the host to these organisms and/or toxins that the organisms produce.
Symptoms, physical examination results, and/or laboratory test results related to the connective and soft tissue.
A malignant fibroblastic neoplasm arising from the soft tissue. It is characterized by the presence of spindle-shaped cells, cellular pleomorphism, thin-walled blood vessels, fibrous septa, and myxoid stroma.
Malocclusion in which the mandible is posterior to the maxilla as reflected by the relationship of the first permanent molar (distoclusion).
Past events that occurred between individuals and/or their communities.
An antiquated term that refers to a non-Hodgkin lymphoma composed of small and medium sized lymphocytes.
The property of lacking physical strength.
An amino- bisphosphonate with anti-resorptive and anti-hypercalcemic activities. Pamidronic acid binds to and adsorbs onto hydroxyapatite crystals in the bone matrix, thereby preventing osteoclast resorption. This agent also binds to and inhibits farnesyl pyrophosphate synthase, an enzyme that plays an important role in the mevalonate pathway. This inhibits the formation of isoprenoid metabolites that are substrates for protein prenylation. This prevents farnesylation and geranylgeranylation of proteins essential for osteoclast function, leading to the induction of apoptosis of osteoclasts. By preventing osteoclast-mediated bone resorption, pamidronic acid decreases bone turnover rate, stabilizes the bone matrix and reduces hypercalcemia.
A congenital anomaly of the kidney and urinary tract in which one or both kidneys are large, distended by multiple cysts, and non-functional. Global prevalence is not known, but the unilateral form is the most frequent. The disorder frequently presents antenatally at routine ultrasound scan. Bilateral disease is considered a lethal entity and most pregnancies are terminated. The disorder results from disrupted nephrogenesis but the exact pathogenic mechanism is still unknown. Mutations in the HNF1B gene (17q12) are strongly associated with the development of this disease. Most cases are sporadic.
Inflammation of the lungs caused by the inhalation or aspiration of chemicals.
The condition of being stretched beyond normal dimensions.
Overproduction of thyroid hormone due to a disorder originating within the thyroid gland.
A cluster of closely related metabolic abnormalities associated with insulin resistance that confer an increased risk of the development of type 2 diabetes and cardiovascular disease. These abnormalities may include obesity, high blood pressure, abnormal cholesterol levels, proteinuria, and/or polycystic ovary syndrome.
Chronic pain caused by damage to nerve fibers. It is usually associated with tissue injury.
Infections with viruses of the genus RESPIROVIRUS, family PARAMYXOVIRIDAE. Host cell infection occurs by adsorption, via HEMAGGLUTININ, to the cell surface.
An inflammatory process affecting the lung parenchyma. It is a milder form of lung inflammation compared to pneumonia.
An electrocardiographic finding in which impaired conduction or automaticity within the sinus node results in the failure of impulse transmission from the sinoatrial node. This is manifested as dropped P waves during sinus rhythm. (CDISC)
A neoplasm that affects the thymus. Representative examples include thymoma and carcinoma.
An encapsulated or nonencapsulated variant of papillary carcinoma of the thyroid gland characterized by the predominance of follicular structures. The malignant follicular cells display the nuclear features that characterize the papillary adenocarcinomas of the thyroid gland.
An electrocardiographic finding of an ectopic impulse originating in the ventricles. The QRS morphology of these complexes is different from those of supraventricular origin. The QRS duration is often longer and the RR interval preceding the complexes is usually shorter than that of supraventricular beats. (CDISC)
An electrocardiographic finding of intermittent failure of atrial electrical impulse conduction to the ventricles. This is manifest on the ECG by regular P waves which intermittently are not followed by QRS complexes. (CDISC)
The chemical reactions and pathways by which a cell derives energy from inorganic compounds; results in the oxidation of the compounds from which energy is released. [GOC:mah]
A benign or malignant neoplasm arising from mesothelial cells. Mesothelial cells are the lining cells of the pleura and peritoneum. -- 2003
Impaired ability to absorb one or more nutrients from the intestine.
X-linked juvenile retinoschisis is characterized by symmetric bilateral macular involvement with onset in the first decade of life, in some cases as early as age three months. Fundus examination shows areas of schisis (splitting of the nerve fiber layer of the retina) in the macula, sometimes giving the impression of a spoke wheel pattern. Schisis of the peripheral retina, predominantly inferotemporally, occurs in approximately 50% of individuals. Affected males typically have vision of 20/60 to 20/120. Visual acuity often deteriorates during the first and second decades of life but then remains relatively stable until the fifth or sixth decade.
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70. [HPO:probinson]
An older, deprecated term that encompassed three major types of autoimmune or autoinflammatory arthritis in children: systemic-onset, pauciarticular, or polyarticular arthritis. The juvenile rheumatoid arthritis classification system has been replaced by the International League of Associations for Rheumatology (ILAR) juvenile idiopathic arthritis classification system.
Childhood arthritis typically associated with psoriasis.
Insufficient production of growth hormone, which is produced by the anterior pituitary gland. Growth hormone is a major participant in control of growth and metabolism.
A synthetic water-soluble analogue of combretastatin A4, derived from the South African willow bush (Combretum caffrum), with potential vascular-disrupting and antineoplastic activities. Ombrabulin binds to the colchicine binding site of endothelial cell tubulin, inhibiting tubulin polymerization and inducing mitotic arrest and apoptosis in endothelial cells. As apoptotic endothelial cells detach from their substrata, tumor blood vessels collapse; the acute disruption of tumor blood flow may result in tumor necrosis.
Axenfeld-Rieger syndrome is an autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals (Fitch and Kaback, 1978). Systemic anomalies are associated, including dental hypoplasia, failure of involution of periumbilical skin, and maxillary hypoplasia (Alkemade, 1969). Genetic Heterogeneity of Axenfeld-Rieger Syndrome Linkage studies indicate that a second type of Axenfeld-Rieger syndrome maps to chromosome 13q14 (RIEG2; 601499). A third form of Axenfeld-Rieger syndrome (RIEG3; 602482) is caused by mutation in the FOXC1 gene (601090) on chromosome 6p25. See 109120 for a form of Axenfeld-Rieger syndrome associated with partially absent eye muscles, hydrocephalus, and skeletal abnormalities.
Smith-McCort dysplasia is a rare autosomal recessive osteochondrodysplasia characterized by short trunk dwarfism with a barrel-shaped chest, rhizomelic limb shortening, and specific radiologic features including marked platyspondyly with double-humped end-plates, kyphoscoliosis, metaphyseal irregularities, laterally displaced capital femoral epiphyses, and small pelvis with a lace-like appearance of iliac crests. These clinical and radiologic features are also common to Dyggve-Melchior-Clausen syndrome (DMC; 223800), which is distinguished from SMC by the additional feature of mental retardation (summary by Dupuis et al., 2013). For a discussion of genetic heterogeneity of Smith-McCort dysplasia, see SMC1 (607326).
Proximal symphalangism-1A (SYM1A) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and, in some cases, conductive deafness (Strasburger et al., 1965). Genetic Heterogeneity of Proximal Symphalangism Another form of proximal symphalangism (SYM1B; 615298) is caused by mutation in the GDF5 gene (601146).
Multiple system atrophy (MSA) is a distinct clinicopathologic entity that manifests as a progressive adult-onset neurodegenerative disorder causing parkinsonism, cerebellar ataxia, and autonomic, urogenital, and pyramidal dysfunction in various combinations. Two main subtypes are recognized: 'subtype C,' characterized predominantly by cerebellar ataxia, and 'subtype P,' characterized predominantly by parkinsonism. MSA is characterized pathologically by the degeneration of striatonigral and olivopontocerebellar structures and glial cytoplasmic inclusions (GCIs) that consist of abnormally phosphorylated alpha-synuclein (SNCA; 163890) or tau (MAPT; 157140) (Gilman et al., 1998; Gilman et al., 2008; Scholz et al., 2009). 'Subtype C' of MSA has been reported to be more prevalent than 'subtype P' in the Japanese population (65-67% vs 33-35%), whereas 'subtype P' has been reported to be more prevalent than 'subtype C' in Europe (63% vs 34%) and North America (60% vs 13%, with 27% of cases unclassified) (summary by The Multiple-System Atrophy Research Collaboration, 2013). MSA is similar clinically and pathologically to Parkinson disease (PD; 168600) and Lewy body dementia (127750). See also PARK1 (168601), which is specifically caused by mutation in the SNCA gene. Pure autonomic failure manifests as orthostatic hypotension and other autonomic abnormalities without other neurologic involvement. Although there is some phenotypic overlap, the relationship of pure autonomic failure to MSA is unclear (Vanderhaeghen et al., 1970; Schatz, 1996).
MDDGC14 is an autosomal recessive form of muscular dystrophy characterized by onset in early childhood of mild proximal muscle weakness. Some patients may have additional features, such as mild intellectual disability or seizures. It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Carss et al., 2013). Some patients with GMPPB mutations may show features consistent with a congenital myasthenic syndrome (see, e.g., CMS1A; 601462), such as fatigability and decremental compound muscle action potential response to repetitive nerve stimulation; these patients may show a positive therapeutic response to treatment with pyridostigmine (Belaya et al., 2015). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
Myoadenylate deaminase deficiency (MMDD) is an autosomal recessive condition that can manifest as exercise-induced muscle pain, occasionally associated with rhabdomyolysis and/or increased serum creatine kinase, or even infantile hypotonia. However, the finding of homozygous mutations among asymptomatic individuals have suggested to some (e.g., Verzijl et al., 1998) that AMPD1 deficiency may be a harmless entity (summary by Castro-Gago et al., 2011). Genetta et al. (2001) stated that AMPD1 deficiency is the most prevalent genetic disease in humans, the number of people heterozygous approaching 10% of Caucasians and individuals of African descent (Sabina et al., 1989). A small percentage of homozygous-deficient individuals, approximately 1.8% of the population, display symptoms of chronic fatigue and lost productivity as well as a predisposition to stress-related ailments, including heart disease and stroke, according to Genetta et al. (2001).
Otofaciocervical syndrome (OTFCS) is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability (summary by Pohl et al., 2013). Genetic Heterogeneity of Otofaciocervical Syndrome OTFCS2 (615560) is caused by mutation in the PAX1 gene (167411) on chromosome 20p11.
Otofaciocervical syndrome (OTFCS) is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability (summary by Pohl et al., 2013). For a discussion of genetic heterogeneity of otofaciocervical syndrome, see OTFCS1 (166780).
Any monoclonal antibody directed against the cell surface glycoprotein CD2, regardless of the antibody type.
Immunodeficiency-14 is an autosomal dominant primary immunodeficiency characterized by onset of recurrent sinopulmonary and other infections in early childhood. Laboratory studies show defects in both B- and T-cell populations, with an inability to control infection with Epstein Barr-virus (EBV) and cytomegalovirus (CMV). Patient CD8+ T cells are skewed toward differentiation and senescence. Many patients develop lymphadenopathy, mucosal lymphoid aggregates, and/or increased serum IgM. There is also an increased susceptibility to B-cell lymphomas (summary by Lucas et al., 2014).
BBS17 is an autosomal recessive ciliopathy characterized by retinitis pigmentosa, cognitive impairment, obesity, renal dysfunction, and hypogenitalism. Polydactyly, most often postaxial, is also a primary feature of BBS; in BBS17 mesoaxial polydactyly, with fused or Y-shaped metacarpals, is a distinct manifestation (Deffert et al., 2007; Schaefer et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Chronic mucocutaneous candidiasis is characterized by recurrent or persistent infections of the skin, nails, and oral and genital mucosae with Candida albicans, and sometimes by staphylococcal skin infections (summary by Boisson et al., 2013). For a discussion of genetic heterogeneity of familial candidiasis, see CANDF1 (114580).
Neuronal ceroid lipofuscinosis-13 is an autosomal recessive neurodegenerative disorder characterized by adult onset of progressive cognitive decline and motor dysfunction leading to dementia and often early death. Some patients develop seizures. Neurons show abnormal accumulation of autofluorescent material (summary by Smith et al., 2013). Adult-onset neuronal ceroid lipofuscinosis is sometimes referred to as Kufs disease. For a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis (CLN), see CLN1 (256730).
Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Craniosynostosis-3 includes coronal, sagittal, and multisuture forms (Sharma et al., 2013). For discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).
Developmental dysplasia of the hip (DDH) is a debilitating condition characterized by incomplete formation of the acetabulum leading to dislocation of the femur, suboptimal joint function, and accelerated wear of the articular cartilage, resulting in arthritis. Undetected hip dysplasia is the leading cause of osteoarthritis of the hip in young individuals, causing over 40% of cases in that age group (summary by Feldman et al., 2013). For discussion of genetic heterogeneity of developmental dysplasia of the hip, see DDH1 (142700).
Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) is an autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, a characteristic facial appearance, and metabolic abnormalities including insulin resistance and diabetes mellitus. Sensorineural deafness occurs late in the first or second decades of life (summary by Weedon et al., 2013).
An electrocardiographic finding of prolonged PR interval for a specific population. For adults one common threshold is a PR interval greater than 0.20 seconds. Note that other thresholds may be applicable. (CDISC)
A non-malignant neoplasm of the genitourinary system.
Anomaly in the weight-to-height squared ratio, calculated by dividing the individual's weight in kilograms by the square of the individual's height in meters and used as an indicator of obesity and underweight compared to averages.
A reduction in the length of time required for food to pass through the intestines.
Formation of a blood clot (thrombus) in the lumen of the splenic vein or splenic artery.
A fetal heart rate pattern characterized by a smooth, sine wave-like undulating pattern with a cycle frequency of 3 to 5 beats per minute that continues for at least 20 minutes or more.
Fibroblast proliferation and fiber expansion from the portal areas to the lobule.
Increased degradation of fibrin, associated with clot instability and bleeding
A baseline fetal heart rate with an amplitude range that is greater than 25 beats per minute.
A baseline fetal heart rate with a detectable amplitude range that is greater than undetectable but less than or equal to five beats per minute.
Blockage of the lumen of the pulmonary vein.
Variable decelerations that occur with greater than or equal to 50 percent of uterine contractions. They are usually associated with umbilical cord compression.
Progression of polycythemia vera characterized by decreased erythropoiesis and granulopoiesis, reticulin and collagen fibrosis of the bone marrow, leucoerythroblastic reaction in the peripheral blood, poikilocytosis, tear-drop shaped red blood cells, and splenomegaly.
Myelofibrosis that develops in a patient with history of essential thrombocythemia.
Middle aortic coarctation is a rare vascular anomaly characterized by the segmental narrowing of the abdominal and/or distal descending thoracic aorta with varying involvement of the visceral and renal arteries that commonly presents in children and young adults with early onset and refractory hypertension, abdominal angina, lower-limb claudication and that can lead to life-threatening complications associated with severe hypertension (i.e. myocardial infarction, heart failure, aortic rupture, renal insufficiency and intracranial hemorrhage). It may be due to various congenital or acquired causes, but it is most often secondary to an acquired inflammatory disease (i.e. Takayasu arteritis or giant cell arteritis; see these terms).
The i and I antigens of the I blood group system (110800) are carbohydrate structures carried on glycolipids and glycoproteins and are characterized as straight or branched glycochains composed of repeating N-acetyllactosamine (LacNAc) units, respectively. Conversion of i antigen into an I-active structure requires the activity of the I-branching enzyme, beta-1,6-N-acetylglucosaminyltransferase (GCNT2; 600429), which adds the decisive GlcNAc-beta-1-6 branch onto the straight poly-LacNAc chains. Expression of the i and I antigens on red blood cells (RBCs) is reciprocal and developmentally regulated. Adult human RBCs predominantly express I antigen, whereas fetal and neonatal RBCs predominantly express i antigen. After birth, I antigen levels increase gradually as i antigen levels fall, with the normal Ii status of adult RBCs reached after about 13 to 20 months. Mutations that specifically affect 1 of the 3 variants produced by the GCNT2 gene cause the rare adult i phenotype (see 110800), in which adult RBCs are rich in i antigen and contain low levels of I antigen. Mutations that eliminate all 3 GCNT2 variants cause the adult i phenotype with congenital cataract (review by Yu and Lin, 2011).
Coralliform cataracts are characterized by multiple coral-like white opacities that radiate out bilaterally in an axial direction from the center of the lens in a fusiform or spindle-shaped fashion but never actually reach the capsule (summary by Gao et al., 2005).
Mutation in the CRYGS gene has been identified in multiple types of cataract, which have been described as progressive polymorphic anterior, posterior, peripheral cortical, sutural, and lamellar.
Mutations in the VIM gene have been found to cause multiple types of cataract, which have been described as congenital, pulverulent, and posterior polar.
Cataract is an opacification of the lens or lens capsule in the eye and is the most common cause of childhood blindness in the world, with an incidence of 1 to 3 per 10,000 live births. If untreated in infancy or childhood, it frequently causes visual impairment and can result in irreversible amblyopia. Nuclear cataract refers to opacification within the embryonal and/or fetal nuclei of the lens (summary by Berry et al., 2013).
A pterygium (or pterygia) occuring in the popliteal region (the back of the knee).
Underdevelopment of the muscuklature of the calf.
Foveal hypoplasia is defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Foveal hypoplasia as an isolated entity is a rare phenomenon; it is usually described in association with other ocular disorders, such as aniridia (106210), microphthalmia (see 251600), albinism (see 203100), or achromatopsia (see 216900). All reported cases of foveal hypoplasia have been accompanied by decreased visual acuity and nystagmus (summary by Perez et al., 2014). Genetic Heterogeneity of Foveal Hypoplasia Foveal hypoplasia-2 (FVH2; 609218) is caused by mutation in the SLC38A8 gene (615585) on chromosome 16q23.
Hypertrophy (increase in size) of muscle cells in a generalized (not localized) distribution.
A disc-shaped patch(es) of skin inflammation that is red, raised, and scaly; it typically develops on the face, scalp, and neck, and often leaves scars and dyspigmentation as a result of postinflammatory hyperpigmentation.
Underdevelopment of the latissimus dorsi muscle, which is involved in adduction, extension, internal rotation, and transverse extension of the shoulder and assists in movement of the scapula.
Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty, which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. The timing of puberty is associated with risks of subsequent disease: earlier age of menarche in girls is associated with increased risk of breast cancer, endometrial cancer, obesity, type 2 diabetes, and cardiovascular disease. Central precocious puberty has also been associated with an increased incidence of conduct and behavior disorders during adolescence (summary by Abreu et al., 2013). Genetic Heterogeneity of Central Precocious Puberty Central precocious puberty-2 (CPPB2; 615346) is caused by mutation in the MKRN3 gene (603856) on chromosome 15q11.
Accumulation of abnormal amounts of pigment within the trabecular meshwork.
A difference in the amount of intraocular pressure in the right and left eye.
An elevation in the ratio of the diameter of the cup of the optic disc to the total diameter of the disc. The optic disc has an orange-pink rim with a pale centre (the cup) that does not contain neuroretinal tissue. An increase in this ratio therefoy may indicate a decrease in the quantity of healthy neuroretinal cells.
An abnormally elevated blood pressure in the circulation of the pulmonary artery.
A recurrent hemorrhage occurring within the lung.
Atrophy of the muscles that are responsible for moving the scapula, which are the levator scapulae, the infraspinatus muscle, the teres major, the teres minor, and the supraspinatus muscle.
Abnormal shortening of the larynx in the anteroposterior (front to back) axis.
Hypochromic microcytic anemia with iron overload is a condition that impairs the normal transport of iron in cells. Iron is an essential component of hemoglobin, which is the substance that red blood cells use to carry oxygen to cells and tissues throughout the body. In this condition, red blood cells cannot access iron in the blood, so there is a decrease of red blood cell production (anemia) that is apparent at birth. The red blood cells that are produced are abnormally small (microcytic) and pale (hypochromic). Hypochromic microcytic anemia with iron overload can lead to pale skin (pallor), tiredness (fatigue), and slow growth.In hypochromic microcytic anemia with iron overload, the iron that is not used by red blood cells accumulates in the liver, which can impair its function over time. The liver problems typically become apparent in adolescence or early adulthood.
BBS18 is an autosomal recessive ciliopathy described in a single patient and characterized by retinitis pigmentosa, obesity, kidney failure, and cognitive disability (Scheidecker et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
The presence of large spherical melanosomes (1 to 6 micrometer in diameter) in the cytoplasm of melanocytes.
Deposition of calcium salts in a tissue or location in which calcification does not normally occur.
Deafness and myopia (DFNMYP) syndrome is characterized by bilateral, congenital or prelingual deafness (sensorineural hearing loss or auditory neuropathy spectrum disorder) and high myopia (>-6 diopters). In individuals with a molecularly confirmed diagnosis reported to date, hearing loss was progressive and severity ranged from moderate to profound. Vestibular testing was normal. Myopia was diagnosed at infancy or early childhood.
Increased susceptibility to infections due to aspiration, as manifested by recurrent episodes of infections due to aspiration.
Reduced tendency to respond to a reduced concentration of oxygen in the blood by increasing respiration.
Subcutaneous nodules that are located in the vicinity of joints.
An increased concentration of homocystine in the blood.
GRIN2A-related speech disorders and epilepsy are characterized by speech disorders in all affected individuals and a range of epilepsy syndromes present in about 90%. Severe speech disorders observed can include dysarthria and speech dyspraxia, and both receptive and expressive language delay/regression; more mildly affected individuals may display subtly impaired intelligibility of conversational speech. Epilepsy features include seizure onset usually between ages three and six years, focal epilepsy with language and/or global developmental regression, and electroencephalogram (EEG) showing continuous spike-and-wave discharges in sleep or very active centrotemporal discharges. Seizure types include seizures associated with aura of perioral paresthesia, focal or focal motor seizures (often evolving to generalized tonic-clonic), and atypical absence seizures. Epilepsy syndromes can include: Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), childhood epilepsy with centrotemporal spikes (CECTS), atypical childhood epilepsy with centrotemporal spikes (ACECTS), autosomal dominant rolandic epilepsy with speech dyspraxia (ADRESD), and infantile-onset epileptic encephalopathy.
Diffuse, bilateral and recently also unilateral or focal localization spike-wave occurring in slow sleep or non-rapid eye movement sleep.
Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).
Increased concentration of taurine in the urine.
Recurrent episodes of apnea that are precipitated by factors such as illness, fatigue, or stress.
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
A horizontal (flat) conformation of the ribs, the long curved bones that form the rib cage and normally progressively oblique (slanted) from ribs 1 through 9, then less slanted through rib 12.
A morphological abnor,mality of the scapula in which there is a flat (horizontal) inferior edge of the scapula. The entire scapula is said to resemble a square, leading to the designation sqaring of the scapula (in Figure 1 of PMID:24706940 the scapulae have a roughly rectangular shape).
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk and with onset in infancy.
Deafness, dystonia, and cerebral hypomyelination is an X-linked recessive mental retardation syndrome characterized by almost no psychomotor development, dysmorphic facial features, sensorineural deafness, dystonia, pyramidal signs, and hypomyelination on brain imaging (summary by Cacciagli et al., 2013).
Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired hemolytic anemia that often manifests with hemoglobinuria, abdominal pain, smooth muscle dystonias, fatigue, and thrombosis. The disease results from the expansion of hematopoietic stem cells harboring a mutation in the PIGA gene, which encodes a protein required for the biosynthesis of glycosylphosphatidylinositol (GPI), a lipid moiety that attaches dozens of proteins to the cell surface. Thus, PNH cells are deficient in cell surface GPI-anchored proteins. This deficiency on erythrocytes leads to intravascular hemolysis, since certain GPI-anchored proteins (i.e., CD55 (125240) and CD59 (107271)) normally function as complement regulators. Free hemoglobin released from intravascular hemolysis leads to circulating nitrous oxide depletion and is responsible for many of the clinical manifestations of PNH, including fatigue, erectile dysfunction, esophageal spasm, and thrombosis (review by Brodsky, 2008). Genetic Heterogeneity of Paroxysmal Nocturnal Hemoglobinuria See also PNH2 (615399), which may be caused by germline and somatic mutation in the PIGT gene (610272) on chromosome 20q13.
Congenital disorder of glycosylation type IIm, or early infantile epileptic encephalopathy-22, is an X-linked dominant severe neurologic disorder characterized by infantile-onset seizures, hypsarrhythmia, hypotonia, and severe intellectual disability with lack of speech. Brain malformations include cerebral and cerebellar atrophy. Additionally, some patients had dysmorphic features or coarse facies (Ng et al., 2013; Kodera et al., 2013). For a general discussion of CDGs, see CDG1A (212065) and CDG2A (212066). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Approximately 40 million people take ACE inhibitors (ACEi) to treat hypertension and cardiovascular disease. A small proportion of white patients who take ACEi (0.1-0.7%) develop angioedema (AEACEI) (Israili and Hall, 1992; Vleeming et al., 1998), a potentially life-threatening side effect characterized by swelling of the face, lips, tongue, and airway that can lead to suffocation and death if severe. ACEi-associated angioedema is 4 to 5 times more prevalent among African Americans (Brown et al., 1996; Coats, 2002). Other risk factors include female sex, smoking, immunosuppressant therapy, and seasonal allergies. The pathophysiology of ACEi-associated angioedema is thought to be related to increased circulating bradykinin, which is normally degraded by ACE. During pharmacologic ACE inhibition, bradykinin is primarily degraded by aminopeptidase P (summary by Duan et al., 2005 and Woodard-Grice et al., 2010). Aminopeptidase P is encoded by 3 genes: XPNPEP1 (602443) on chromosome 10q25, XPNPEP2 (300145) on chromosome Xq25, and XPNPEP3 (613553) on chromosome 22q13.
X-linked mental retardation-98 is a neurodevelopmental disorder characterized by delayed psychomotor development, poor speech, behavioral abnormalities, poor overall growth, dysmorphic facial features, and often early-onset seizures. Some carrier females are unaffected, whereas other females with mutations are affected; males tend to be more severely affected than females. It is believed that the phenotypic variability and disease manifestations in female carriers results from skewed X-inactivation or cellular mosaicism (summary by de Lange et al., 2016).
Olmsted syndrome is a rare keratinization disorder characterized by the combination of periorificial keratotic plaques and bilateral palmoplantar transgredient keratoderma. Other clinical manifestations include diffuse alopecia, leukokeratosis of the oral mucosa, onychodystrophy, hyperkeratotic linear streaks, follicular keratosis, and constriction of the digits (summary by Yaghoobi et al., 2007). An autosomal dominant form of Olmsted syndrome (614594) is caused by mutation in the TRPV3 gene (607066) on chromosome 17p13.
Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Craniosynostosis-4 includes lambdoid, sagittal, metopic, coronal, and multisuture forms. For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).
An abnormal enlargement (i.e. increase in measured voltage) of somatosensory evoked potentials.
Reduced differentiation between renal cortex and medulla on diagnostic imaging.
The congenital dyserythropoietic anemias (CDAs) are an uncommon and heterogeneous group of conditions characterized by increased ineffective erythropoiesis and, usually, dysplastic changes in erythroblasts. Originally, 3 types of CDA were recognized and designated CDA type I (224120), type II (224100), and type III (105600). Subsequently, a number of other types were described, as reviewed by Wickramasinghe (1997). The defining features of CDA type I are autosomal recessive inheritance, macrocytes in the peripheral blood, internuclear chromatin bridges connecting some almost completely separated erythroblasts, and an abnormal ultrastructural appearance (spongy or 'swiss-cheese' appearance) of the heterochromatin in a high proportion of the erythroblasts.
ADCADN is an autosomal dominant neurologic disorder characterized by adult onset of progressive cerebellar ataxia, narcolepsy/cataplexy, sensorineural deafness, and dementia. More variable features include optic atrophy, sensory neuropathy, psychosis, and depression (summary by Winkelmann et al., 2012).
Advanced sleep phase syndrome is characterized by very early sleep onset and offset (summary by Jones et al., 1999). Genetic Heterogeneity of Advanced Sleep Phase Syndrome See also FASPS2 (615224), caused by mutation in the CSNK1D gene (600864) on chromosome 17q25, and FASPS3 (616882), caused by mutation in the PER3 gene (603427) on chromosome 1p36.
Amyotrophic lateral sclerosis-21 is an autosomal dominant neurodegenerative disorder affecting upper and lower motor neurons, resulting in muscle weakness and respiratory failure. Some patients may develop myopathic features or dementia (summary by Johnson et al., 2014). For a discussion of genetic heterogeneity of amyotrophic lateral sclerosis, see ALS1 (105400).
Lennox-Gastaut syndrome is a severe condition characterized by recurrent seizures (epilepsy) that begin early in life. Affected individuals have multiple types of seizures, a particular pattern of brain activity (called slow spike-and-wave) measured by a test called an electroencephalogram (EEG), and impaired mental abilities.In Lennox-Gastaut syndrome, epilepsy begins in early childhood, usually between ages 3 and 5. The most common seizure type is tonic seizures, which cause the muscles to stiffen (contract) uncontrollably. These seizures typically occur during sleep; they may also occur during wakefulness and cause sudden falls. Also common are atypical absence seizures, which cause a very brief partial or complete loss of consciousness. Additionally, many affected individuals have episodes called drop attacks, which cause sudden falls that can result in serious or life-threatening injuries. Drop attacks may be caused by sudden loss of muscle tone (described as atonic) or by abnormal muscle contraction (described as tonic). Other types of seizures have been reported less frequently in people with Lennox-Gastaut syndrome. Seizures associated with Lennox-Gastaut syndrome often do not respond well to therapy with anti-epileptic medications.Although each seizure episode associated with Lennox-Gastaut syndrome is usually brief, more than two-thirds of affected individuals experience prolonged periods of seizure activity (known as status epilepticus) or episodes of many seizures that occur in a cluster.Most children with Lennox-Gastaut syndrome have intellectual disability or learning problems even before seizures begin. These problems may worsen over time, particularly if seizures are very frequent or severe. Some affected children develop additional neurological abnormalities and behavioral problems. Many also have delayed development of motor skills such as sitting and crawling. As a result of their seizures and intellectual disability, most people with Lennox-Gastaut syndrome require help with the usual activities of daily living. However, a small percentage of affected adults live independently.People with Lennox-Gastaut syndrome have a higher risk of death than their peers of the same age. Although the increased risk is not fully understood, it is partly due to poorly controlled seizures and injuries from falls.
Lipodystrophies are rare disorders characterized by loss of body fat from various regions and predisposition to metabolic complications of insulin resistance and lipid abnormalities. FPLD7 is an autosomal dominant disorder with a highly variable phenotype. Additional features, including early-onset cataracts and later onset of spasticity of the lower limbs, have been noted in some patients (summary by Garg et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.
Foveal hypoplasia is defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Foveal hypoplasia as an isolated entity is a rare phenomenon; it is usually described in association with other ocular disorders, such as aniridia (106210), microphthalmia (see 251600), albinism (see 203100), or achromatopsia (see 216900). All reported cases of foveal hypoplasia have been accompanied by decreased visual acuity and nystagmus (summary by Perez et al., 2014). For a discussion of genetic heterogeneity of foveal hypoplasia, see FVH1 (136520).
Recurrent episodes of apnea occurring during infancy.
An intermittent form of abdominal pain. [HPO:probinson]
Nemaline rods are abnormal bodies that can occur in skeletal muscle fibers. The rods can be observed on histological analysis of muscle biopsy tissue or upon electron microscopy, where they appear either as extensions of sarcomeric Z-lines, in random array without obvious attachment to Z-lines (often in areas devoid of sarcomeres) or in large clusters localized at the sarcolemma or intermyofibrillar spaces.
Mutations in the BFSP1 gene have been found to cause multiple types of cataract, which have been described as cortical, nuclear, and progressive punctate lamellar. Both autosomal dominant and autosomal recessive modes of inheritance have been reported.
Mutations in the BFSP2 gene have been found to cause multiple types of cataract, which have been described as juvenile-onset lamellar, cortical, nuclear embryonic; and congenital nuclear, sutural, stellate, Y-sutural, and punctate cortical.
MRD22 is characterized by impaired intellectual development with frequent cooccurrence of corpus callosum anomalies, hypotonia, microcephaly, growth problems, and variable facial dysmorphism (summary by van der Schoot et al., 2018). Chromosome 1q43-q44 deletion syndrome is characterized by moderate to severe mental retardation, limited or no speech, and variable but characteristic facial features, including round face, prominent forehead, flat nasal bridge, hypertelorism, epicanthal folds, and low-set ears. Other features may include hypotonia, poor growth, microcephaly, agenesis of the corpus callosum, and seizures. The phenotype is variable, and not all features are observed in all patients, which may be explained in some cases by incomplete penetrance or variable expressivity (summary by Ballif et al., 2012).
A morphological abnormality of the optic disc, i.e., of the portion of the optic nerve clinically visible on fundoscopic examination.
The presence of osteophytes (bone spurs), i.e., of bony projections originating from the acetabulum.
Mutations in the CRYAB gene have been found to cause multiple types of cataract, which have been described as congenital posterior polar, congenital lamellar, and juvenile. Autosomal dominant and autosomal recessive forms have been described. The preferred title/symbol of this entry was formerly 'Cataract, Posterior Polar, 2; CTPP2.'
Complex cortical dysplasia with other brain malformations (CDCBM) is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved (summary by Poirier et al., 2010). Mutation in the TUBB3 gene can also cause congenital fibrosis of extraocular muscles-3A (CFEOM3A; 600638), a milder and somewhat different neurologic phenotype. Genetic Heterogeneity of Complex Cortical Dysplasia With Other Brain Malformations See also CDCBM2 (615282), caused by mutation in the KIF5C gene (604593) on chromosome 2q23; CDCBM3 (615411), caused by mutation in the KIF2A gene (602591) on chromosome 5q12; CDCBM4 (615412), caused by mutation in the TUBG1 gene (191135) on chromosome 17q21; CDCBM5 (615763), caused by mutation in the TUBB2A gene (615101) on chromosome 6p25; CDCBM6 (615771), caused by mutation in the TUBB gene (191130) on chromosome 6p21; CDCBM7 (610031), caused by mutation in the TUBB2B gene (612850) on chromosome 6p25; CDCBM8 (613180), caused by mutation in the TUBA8 gene (605742) on chromosome 22q11; and CDCBM9 (618174), caused by mutation in the CTNNA2 gene (114025) on chromosome 2p12. See also lissencephaly (e.g., LIS1, 607432), which shows overlapping features and may result from mutation in tubulin genes.
Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility to autism, schizophrenia (SCZD17), developmental delay, intellectual disability, and dysmorphic features. The phenotype is highly variable and shows incomplete penetrance (summary by Dabell et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of schizophrenia, see 181500.
Autosomal dominant IRF8 deficiency, or IMD32A, causes an abnormal peripheral blood myeloid phenotype with a marked loss of CD11C (ITGAX; 151510)-positive/CD1C (188340) dendritic cells, resulting in selective susceptibility to mycobacterial infections (Hambleton et al., 2011).
Familial episodic pain syndrome-1 is an autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress (summary by Kremeyer et al., 2010). Genetic Heterogeneity of Familial Episodic Pain Syndrome See also FEPS2 (615551), caused by mutation in the SCN10A gene (604427) on chromosome 3p22, and FEPS3 (615552), caused by mutation in the SCN11A gene (604385) on chromosome 3p22.
Mutations in the CRYGB gene have been found to cause multiple types of cataract, which have been described as lamellar, anterior polar, and complete.
Increased susceptibility to gastroenteritis, an infectious inflammationof the stomach and small intestines manifested by signs and symptoms such as diarheas and abdominal pain, as manifested by recurrent episodes of gastroenteritis.
Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most forms of OI are autosomal dominant with mutations in one of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160). Keupp et al. (2013) and Pyott et al. (2013) described osteogenesis imperfecta type XV, an autosomal recessive form of the disorder characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclera. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients.
Advanced sleep phase syndrome is characterized by very early sleep onset and offset (summary by Jones et al., 1999). For a discussion of genetic heterogeneity of advanced sleep phase syndrome, see FASPS1 (604348).
Multiple self-healing palmoplantar carcinoma (MSPC) is characterized by recurrent keratoacanthomas in palmoplantar skin as well as in conjunctival and corneal epithelia. In addition, patients experience a high susceptibility to malignant squamous cell carcinoma (summary by Zhong et al., 2016).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with congenital muscular dystrophy resulting in muscle weakness early in life and brain and eye anomalies. It is usually associated with delayed psychomotor development and shortened life expectancy. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as dystroglycanopathies (summary by Stevens et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Individuals with NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) typically display a clinical tetrad of developmental delay / intellectual disability in the mild to profound range, hypo- or alacrima, elevated liver transaminases that may spontaneously resolve in childhood, and a complex hyperkinetic movement disorder that can include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. About half of affected individuals will develop clinical seizures. Other findings may include obstructive and/or central sleep apnea, oral motor defects that affect feeding ability, auditory neuropathy, constipation, scoliosis, and peripheral neuropathy.
Mutations in the MIP gene have been found to cause multiple types of cataract, which have been described as 'polymorphic,' progressive punctate lamellar, cortical, anterior and posterior polar, nonprogressive lamellar with sutural opacities, embryonic nuclear, and pulverulent cortical.
Mutation in the LIM2 gene has been identified in 1 family with cataracts described as late-onset cortical pulverulent and in another family with congenital cataracts described as total.
Hypomyelination with brainstem and spinal cord involvement and leg spasticity is an autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation. Affected individuals show delayed motor development and nystagmus; some may have mild mental retardation. Brain MRI shows hypomyelination and white matter lesions in the cerebrum, brainstem, cerebellum, and spinal cord (summary by Taft et al., 2013).
Severe congenital neutropenia-5 is an autosomal recessive primary immunodeficiency disorder characterized primarily by neutropenia and neutrophil dysfunction, a lack of response to G-CSF, life-threatening infections, bone marrow fibrosis, and renal extramedullary hematopoiesis (summary by Vilboux et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is a autosomal recessive disorder associated with severe neurologic defects and resulting in early infantile death. The phenotype includes the alternative clinical designations Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as dystroglycanopathies (summary by Buysse et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
SMALED2A is an autosomal dominant form of spinal muscular atrophy characterized by early childhood onset of muscle weakness and atrophy predominantly affecting the proximal and distal muscles of the lower extremity, although some patients may show upper extremity involvement. The disorder results in delayed walking, waddling gait, difficulty walking, and loss of distal reflexes. Some patients may have foot deformities or hyperlordosis, and some show mild upper motor signs, such as spasticity. Sensation, bulbar function, and cognitive function are preserved. The disorder shows very slow progression throughout life (summary by Oates et al., 2013). For discussion of genetic heterogeneity of lower extremity-predominant spinal muscular atrophy, see SMALED1 (158600).
Infantile myofibromatosis is a disorder of mesenchymal proliferation characterized by the development of benign tumors in the skin, muscle, bone, and viscera. Soft tissue lesions may regress spontaneously. Visceral lesions are associated with high morbidity and mortality (summary by Martignetti et al., 2013). For a discussion of genetic heterogeneity of infantile myofibromatosis, see IMF1 (228550).
Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmentation, usually in a flexural distribution. However, generalized DDD can also occur, with numerous hypopigmented or erythematous macules and papules on the neck, chest, and abdomen. The histopathology of DDD shows characteristic thin branch-like patterns of epidermal downgrowth (summary by Li et al., 2013). Review of Reticulate Pigment Disorders Muller et al. (2012) reviewed the spectrum of reticulate pigment disorders of the skin, tabulating all reported cases of patients with Dowling-Degos disease, reticulate acropigmentation of Kitamura (RAK), reticulate acropigmentation of Dohi (DSH, RAD; 127400), Galli-Galli disease (GGD), and Haber syndrome (HS). Of 82 cases, 26 (31.7%) were clinically diagnosed as DDD, 13 (15.9%) as RAD, 11 (13.4%) as GGD, 8 (9.8%) as RAK, and 8 (9.8%) as HS; in addition, 16 (19.5%) of the cases showed overlap between DDD and RAK. Muller et al. (2012) also published photographs of an affected individual exhibiting an overlap of clinical features of DDD, GGD, RAD, and RAK. The authors noted that in reticulate disorders of the skin, the main disease entity is DDD, with a subset of cases exhibiting acantholysis (GGD), facial erythema (HS), or an acral distribution (RAD; RAK). Muller et al. (2012) concluded that all reticulate pigment diseases of the skin are varying manifestations of a single entity. For a discussion of genetic heterogeneity of reticulate pigment disorders, see 179850.
Shaheen syndrome is an autosomal recessive form of syndromic mental retardation. Affected individuals show severe intellectual disability, hypohidrosis, dental enamel hypoplasia, and hyperkeratosis of the palms and soles. Some may develop mild microcephaly (summary by Shaheen et al., 2013).
MMDS3 is an autosomal recessive severe neurodegenerative disorder characterized by loss of previously acquired developmental milestones in the first months or years of life. Some affected patients have normal development in early infancy before the onset of symptoms, whereas others show delays from birth. Features included loss of motor function, spasticity, pyramidal signs, loss of speech, and cognitive impairment. The disease course is highly variable: some patients die of respiratory failure early in childhood, whereas some survive but may be bedridden with a feeding tube. Less commonly, some patients may survive and have a stable course with motor deficits and mild or even absent cognitive impairment, although there may be fluctuating symptoms, often in response to infection. Other variable features include visual problems and seizures. Brain imaging shows diffuse leukodystrophy in the subcortical region, brainstem, cerebellum, and spinal cord. Laboratory studies tend to show increased lactate and CSF glycine, and decreased activity of mitochondrial complexes I and II, although these findings are also variable. There may be additional biochemical evidence of mitochondrial dysfunction (summary by Liu et al., 2018). For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711).
Pulmonary arterial hypertension (PAH) is characterized by widespread obstruction and obliteration of the smallest pulmonary arteries. When a sufficient number of vessels are occluded, the resistance to blood flow through the lungs increases, and the right ventricle attempts to compensate by generating higher pressure to maintain pulmonary blood flow. When the right ventricle can no longer compensate for the increased resistance, progressive heart failure ensues. Initial symptoms include dyspnea (60%), fatigue (19%), syncope (8%), chest pain (7%), palpitations (5%), and leg edema (3%). All ages are affected, but the mean age at diagnosis is 36 years. Mean survival after diagnosis is 2.8 years; current therapy does improve clinical function but has modest effect on survival. The term ""heritable PAH"" (HPAH) includes familial PAH (PAH that occurs in two or more family members) and simplex PAH (i.e., a single occurrence in a family) when a pathogenic variant has been identified. Most heritable PAH (75%) is caused by a pathogenic variant in BMPR2; pathogenic variants in other genes (i.e., ACVRL1, KCNK3, CAV1, SMAD9, BMPR1B) are considerably less common (1%-3%). HPAH has identical symptoms, signs, and histology as PAH of unknown cause. The time from onset of symptoms to diagnosis may be shorter in individuals with familial PAH, possibly because of familial awareness of the disease. Three retrospective studies suggest that persons with PAH who have a BMPR2 pathogenic variant exhibit more severe disease.
Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty, which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. The timing of puberty is associated with risks of subsequent disease: earlier age of menarche in girls is associated with increased risk of breast cancer, endometrial cancer, obesity, type 2 diabetes, and cardiovascular disease. Central precocious puberty has also been associated with an increased incidence of conduct and behavior disorders during adolescence (summary by Abreu et al., 2013). For discussion of genetic heterogeneity of central precocious puberty, see CPPB1 (176400).
The features of Ehlers-Danlos syndrome spondylodysplastic type 2 include an aged appearance, developmental delay, short stature, craniofacial disproportion, generalized osteopenia, defective wound healing, hypermobile joints, hypotonic muscles, and loose but elastic skin (Okajima et al., 1999). For a discussion of genetic heterogeneity of the spondylodysplastic type of Ehlers-Danlos syndrome, see 130070.
MDDGB14 is an autosomal recessive congenital muscular dystrophy characterized by severe muscle weakness apparent in infancy and mental retardation. Some patients may have additional features, such as microcephaly, cardiac dysfunction, seizures, or cerebellar hypoplasia. It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Carss et al., 2013). For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
Estrogen resistance (ESTRR) is characterized by absence of puberty with elevated estradiol and gonadotropic hormones, as well as markedly delayed bone maturation. Female patients show absent breast development, small uterus, and enlarged multicystic ovaries; male patients may show small testes (Bernard et al., 2017). Some patients exhibit continued growth into adulthood (Smith et al., 1994).
CHD2-related neurodevelopmental disorders are characterized by early-onset epileptic encephalopathy (i.e., refractory seizures and cognitive slowing or regression associated with frequent ongoing epileptiform activity). Seizure onset is typically between ages six months and four years. Seizure types typically include drop attacks, myoclonus, and a rapid onset of multiple seizure types associated with generalized spike-wave on EEG, atonic-myoclonic-absence seizures, and clinical photosensitivity. Intellectual disability and/or autism spectrum disorders are common. To date only 32 individuals with a CHD2-related neurodevelopmental disorder have been reported; thus, better understanding of the phenotypic spectrum of CHD2-related neurodevelopmental disorders is likely to evolve over time.
Increased amount of pigmentation in the fovea centralis.
CMTRIC is an autosomal recessive peripheral neuropathy characterized by distal sensory impairment predominantly affecting the lower limbs and resulting in walking difficulties due to muscle weakness and atrophy. The upper limbs may also be affected. Electrophysiologic studies and sural nerve biopsy show mixed features of demyelinating and axonal neuropathy. The age at onset and the severity of the disease are variable (summary by Azzedine et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive intermediate CMT, see CMTRIA (608340).
Autosomal recessive spinocerebellar ataxia-14 is a neurologic disorder characterized by delayed psychomotor development, severe early-onset gait ataxia, eye movement abnormalities, cerebellar atrophy on brain imaging, and intellectual disability (summary by Lise et al., 2012).
Multiple congenital anomalies-hypotonia-seizures syndrome is an autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, seizures, dysmorphic features, and variable congenital anomalies involving the cardiac, urinary, and gastrointestinal systems. Most affected individuals die before 3 years of age (summary by Maydan et al., 2011). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of MCAHS, see MCAHS1 (614080). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Familial adult myoclonic epilepsy-5 is an autosomal recessive neurologic disorder characterized by onset of seizures in adolescence, followed by the development of cortical myoclonic tremor later in life. Some patients may also have neuropsychiatric abnormalities (summary by Stogmann et al., 2013).
Dyschromatosis universalis hereditaria (DUH) is a rare autosomal dominant genodermatosis characterized by irregularly shaped asymptomatic hyper- and hypopigmented macules that appear in infancy or early childhood and occur in a generalized distribution over the trunk, limbs, and sometimes the face. Involvement of the palms or soles is unusual. Abnormalities of hair and nails have been reported, and DUH may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications (summary by Zhang et al., 2013). For a discussion of genetic heterogeneity of DUH, see DUH1 (127500).
RHPD2 is an autosomal recessive multisystemic disorder with severe abnormalities apparent in utero and often resulting in fetal death or death in infancy. The main organs affected include the kidney, liver, and pancreas, although other abnormalities, including cardiac, skeletal, and lung defects, may also be present. Affected individuals often have situs inversus. The disorder results from a defect in ciliogenesis and ciliary function, as well as in cell proliferation and epithelial morphogenesis; thus, the clinical manifestations are highly variable (summary by Grampa et al., 2016). For a discussion of genetic heterogeneity of renal-hepatic-pancreatic dysplasia, see RHPD1 (208540).
Mitochondrial DNA depletion syndrome-12B is an autosomal recessive mitochondrial disorder characterized by childhood onset of slowly progressive hypertrophic cardiomyopathy and generalized skeletal myopathy resulting in exercise intolerance, and, in some patients, muscle weakness and atrophy. Skeletal muscle biopsy shows ragged-red fibers, mtDNA depletion, and accumulation of abnormal mitochondria (summary by Echaniz-Laguna et al., 2012). For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).
Infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) is a severe autosomal recessive neurologic disorder with onset at birth or in early infancy. Affected individuals show very poor, if any, normal cognitive development. Some patients are never learn to sit or walk independently (summary by Al-Sayed et al., 2013). Genetic Heterogeneity of Infantile Hypotonia with Psychomotor Retardation and Characteristic Facies See also IHPRF2 (616801), caused by mutation in the UNC80 gene (612636) on chromosome 2q34; and IHPRF3 (616900), caused by mutation in the TBCK gene (616899) on chromosome 4q24.
EBSB2 is a mild autosomal recessive dermatologic disorder characterized by trauma-induced blistering mainly occurring on the feet and ankles. Ultrastructural analysis of skin biopsy shows abnormal hemidesmosomes with poorly formed inner plaques (summary by Liu et al., 2012).
Specific language impairment-5 is characterized by a delay in early speech acquisition and is usually associated with cerebral white matter abnormalities on brain MRI. Some individuals may show disorders in communication, consistent with autism spectrum disorder, or global developmental delay, although others ultimately show normal cognitive function. Penetrance is incomplete and expressivity is variable. This type of disorder is observed most commonly among individuals of East Asian descent (summary by Wiszniewski et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of specific language impairment, see SLI1 (602081).
The chromosome 3q13.31 deletion syndrome is characterized by marked developmental delay, characteristic facies with a short philtrum and protruding lips, and abnormal male genitalia (Molin et al., 2012). Patients with Primrose syndrome (PRIMS; 259050) exhibit features overlapping those of the chromosome 3q13.31 deletion syndrome but also have ossified ear cartilage, severe muscle wasting, and abnormalities of glucose metabolism resulting in insulin-resistant diabetes mellitus in adulthood. Primrose syndrome is caused by mutation in the ZBTB20 gene (606025) on chromosome 3q13.
Age-related macular degeneration (ARMD) is a multifactorial disorder of the central retina that is the most prevalent cause of progressive vision loss in the developed world. As in other chronic age-related diseases, most cases result from interplay between multiple environmental and genetic factors, with a resultant spectrum of phenotypes. In rare cases, ARMD may manifest early, but there is an exponential rise in prevalence after the age of 60 years (summary by Pras et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration (ARMD), see 603075.
Combined oxidative phosphorylation deficiency-17 is an autosomal recessive disorder of mitochondrial dysfunction characterized by onset of severe hypertrophic cardiomyopathy in the first year of life. Other features include hypotonia, poor growth, lactic acidosis, and failure to thrive. The disorder may be fatal in early childhood (summary by Haack et al., 2013).
Mitochondrial complex III deficiency nuclear type 6 (MC3DN6) is an autosomal recessive disorder caused by mitochondrial dysfunction. It is characterized by onset in early childhood of episodic acute lactic acidosis, ketoacidosis, and insulin-responsive hyperglycemia, usually associated with infection. Laboratory studies show decreased activity of mitochondrial complex III. Psychomotor development is normal (summary by Gaignard et al., 2013). For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000).
FBXL4-related encephalomyopathic mitochondrial DNA (mtDNA) depletion syndrome is a multi-system disorder characterized primarily by congenital or early-onset lactic acidosis and growth failure, feeding difficulty, hypotonia, and developmental delay. Other neurologic manifestations can include seizures, movement disorders, ataxia, autonomic dysfunction, and stroke-like episodes. All affected individuals alive at the time they were reported (median age: 3.5 years) demonstrated significant developmental delay. Other findings can involve the heart (hypertrophic cardiomyopathy, congenital heart malformations, arrhythmias), liver (mildly elevated transaminases), eyes (cataract, strabismus, nystagmus, optic atrophy), hearing (sensorineural hearing loss), and bone marrow (neutropenia, lymphopenia). Survival varies; the median age of reported deaths was two years (range 2 days - 75 months), although surviving individuals as old as 36 years have been reported. To date FBXL4-related mtDNA depletion syndrome has been reported in 50 individuals.
Early infantile epileptic encephalopathy-17 is a severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life and usually associated with EEG abnormalities. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements (summary by Nakamura et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Early infantile epileptic encephalopathy-18 is a severe autosomal recessive neurologic disorder characterized by lack of psychomotor development apparent from birth, dysmorphic facial features, early onset of refractory seizures, and thick corpus callosum and persistent cavum septum pellucidum on brain imaging (summary by Basel-Vanagaite et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Bainbridge-Ropers syndrome (BRPS) is a developmental disorder characterized by delayed psychomotor development, severe intellectual disability with poor or absent speech, hypotonia, feeding difficulties, poor growth, and dysmorphic facial features (summary by Srivastava et al., 2016).
SPG79 is an autosomal recessive progressive neurologic disorder characterized by onset of spastic paraplegia and optic atrophy in the first decade of life. Additional features are variable, but may include peripheral neuropathy, cerebellar ataxia, and cognitive impairment (summary by Rydning et al., 2017). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Alacrima, achalasia, and mental retardation syndrome (AAMR) is an autosomal recessive disorder characterized by onset of these 3 main features at birth or in early infancy. More variable features include hypotonia, gait abnormalities, anisocoria, and visual or hearing deficits. The disorder shows similarity to the triple A syndrome (231550), but patients with AAMR do not have adrenal insufficiency (summary by Koehler et al., 2013). See also 300858 for a phenotypically similar disorder that shows X-linked inheritance.
Idiopathic CD4 lymphopenia (ICL) is a rare and heterogeneous syndrome defined by a reproducible reduction in the CD4 T-lymphocyte count (less than 300 cells per microliter or less than 20% of total T cells) in the absence of HIV infection or other known causes of immunodeficiency. ICL predisposes to infections and malignancy (summary by Gorska and Alam, 2012).
Cole disease is a rare autosomal dominant disorder characterized by congenital or early-onset punctate keratoderma associated with irregularly shaped hypopigmented macules, which are typically found over the arms and legs but not the trunk or acral regions. Skin biopsies of palmoplantar lesions show nonspecific changes including hyperorthokeratosis, hypergranulosis, and acanthosis. Hypopigmented areas of skin, however, reveal a reduction in melanin content in keratinocytes but not in melanocytes, as well as hyperkeratosis and a normal number of melanocytes. Ultrastructurally, melanocytes show a disproportionately large number of melanosomes in the cytoplasm and dendrites, whereas keratinocytes show a paucity of these organelles, suggestive of impaired melanosome transfer (summary by Eytan et al., 2013). Some patients also exhibit calcinosis cutis or early-onset calcific tendinopathy (Eytan et al., 2013).
Fuchs endothelial corneal dystrophy (FECD) is the most common genetic disorder of the corneal endothelium. Late-onset FECD is marked by thickening of Descemets membrane and excrescences, called guttae, that typically appear in the fourth or fifth decade. Disease progression results in decreased visual acuity as a result of increasing corneal edema, and end-stage disease is marked by painful epithelial bullae (summary by Riazuddin et al., 2013). For a discussion of genetic heterogeneity of FECD, see FECD1 (136800).
Parkinson disease-19A is an autosomal recessive neurodegenerative disorder characterized by onset of parkinsonism in the first or second decade. Some patients may have additional neurologic features, including mental retardation and seizures (summary by Edvardson et al., 2012 and Koroglu et al., 2013). Parkinson disease-19B is an autosomal recessive neurodegenerative disorder with onset of parkinsonism between the third and fifth decades. It is slowly progressive, shows features similar to classic late-onset Parkinson disease (PD), and has a beneficial response to dopaminergic therapy (Olgiati et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
Premature fusion of the various sutures in the human neurocranium (skull vault and base) is defined as craniosynostosis (CRS). Clinical consequences include abnormal head shape and increased intracranial pressure, which may result in neurologic symptoms, developmental delay, and hearing or vision problems. Approximately 80% of cases are classified as nonsyndromic craniosynostosis and present as isolated suture fusion with no other associated anomalies. Sagittal suture fusion is the most common form of isolated craniosynostosis, accounting for 40 to 58% of all isolated cases (summary by Yagnik et al., 2012). For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).
Parkinson disease-20 is an autosomal recessive neurodegenerative disorder characterized by young adult-onset of parkinsonism. Additional features may include seizures, cognitive decline, abnormal eye movements, and dystonia (summary by Krebs et al., 2013 and Quadri et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
An abnormality in which the eyes are held permanently wide open.
The musculocontractural type of Ehlers-Danlos syndrome is characterized by progressive multisystem fragility-related manifestations, including joint dislocations and deformities; skin hyperextensibility, bruisability, and fragility, with recurrent large subcutaneous hematomas; cardiac valvular, respiratory, gastrointestinal, and ophthalmologic complications; and myopathy, featuring muscle hypoplasia, muscle weakness, and an abnormal muscle fiber pattern in histology in adulthood, resulting in gross motor developmental delay (summary by Muller et al., 2013). For a discussion of genetic heterogeneity of the musculocontractural type of Ehlers-Danlos syndrome, see EDSMC1 (601776).
Van Maldergem syndrome is an autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia (summary by Cappello et al., 2013). For a discussion of genetic heterogeneity of Van Maldergem syndrome, see 601390.
SHFYNG syndrome is an autosomal dominant multisystem disorder characterized by delayed psychomotor development, impaired intellectual development, hypotonia, and behavioral abnormalities. Additional features include contractures, feeding difficulties, and variable dysmorphic facial features. The severity of the disorder is highly variable: some patients may die in utero with fetal akinesia, whereas others can live with moderate disability. Individuals are affected only if the mutation occurs on the paternal allele, since MAGEL2 is a maternally imprinted gene (summary by Fountain et al., 2017)
A very rare disorder caused by mutation in the SCN11A gene. Affected individuals are unable to experience pain since birth resulting in self-inflicted injuries.
Familial episodic pain syndrome-2 is an autosomal dominant neurologic disorder characterized by adult-onset of paroxysmal pain mainly affecting the distal lower extremities (summary by Faber et al., 2012). For a discussion of genetic heterogeneity of familial episodic pain syndrome, see 615040.
Familial episodic pain syndrome is an autosomal dominant disorder characterized by early childhood onset of intense episodic pain mainly affecting the distal lower extremities, but sometimes affecting the upper extremities as well. The pain comes in cycles lasting several days, is exacerbated by fatigue, may be accompanied by sweating, and can be relieved by antiinflammatory medication. Severe episodic pain tends to diminish with age (summary by Zhang et al., 2013). For a discussion of the genetic heterogeneity of familial episodic pain syndrome, see FEPS1 (615040).
Fibroadenoma represents a benign breast disease characterized by lobuloalveolar growth with abnormally high proliferation of the epithelium. Patients with more than 3 fibroadenomas in 1 breast are considered to have multiple fibroadenomas (summary by Bogorad et al., 2008).
Melioidosis is infection caused by the gram-negative, flagellated soil saprophyte Burkholderia pseudomallei, which is endemic in parts of southeast Asia and northern Australia. Sepsis is a common clinical presentation of disease, and lung is the organ most commonly involved. In northern Thailand, where B. pseudomallei is the most common bloodstream isolate, the overall melioidosis mortality rate exceeds 40%, and pneumonia confers more than 2-fold increased risk of death (summary by West et al., 2013).
Autoimmune lymphoproliferative syndrome type III is an autosomal recessive disorder of immune dysregulation. The phenotype is variable, but most patients have significant lymphadenopathy associated with variable autoimmune manifestations. Some patients may have recurrent infections. Lymphocyte accumulation results from a combination of impaired apoptosis and excessive proliferation (summary by Oliveira, 2013). For a general description and a discussion of genetic heterogeneity of ALPS, see 601859.
Retinitis pigmentosa (RP) is the name given to a group of hereditary retinal conditions in which degeneration of rod photoreceptors, responsible for vision under dark conditions, is more pronounced than that of cone photoreceptors, which mediate daylight vision. Individuals with RP typically experience night blindness at first, followed by progressive and unstoppable visual impairment in daytime conditions as well. Their visual fields become reduced gradually and sight is lost from the midperiphery to the periphery, then from the midperiphery to the center, resulting eventually in complete or near-complete blindness if left untreated. Most patients show intraretinal pigment in a bone-spicule configuration around the fundus periphery as well as retinal arteriolar attenuation, elevated final dark-adapted thresholds, and reduced and delayed electroretinograms. Autosomal recessive RP is the most common form of hereditary retinal degeneration in humans (summary by Nishiguchi et al., 2013). For a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Nephrotic syndrome type 9 (NPHS9) is an autosomal recessive chronic kidney disorder characterized by significant proteinuria resulting in hypoalbuminemia and edema. Onset is in the first or second decade of life. The disorder is steroid treatment-resistant and usually progresses to end-stage renal disease requiring transplantation. Renal biopsy shows focal segmental glomerulosclerosis (FSGS) or collapsing FSGS (summary by Ashraf et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Asparagine synthetase deficiency (ASD) mainly presents as a triad of congenital microcephaly, severe developmental delay, and axial hypotonia followed by spastic quadriplegia. Low cerebrospinal fluid (CSF) asparagine level can help the clinician in differentiating this disorder from others. In most cases age of onset of apnea, excessive irritability, and seizures is soon after birth. Affected individuals typically do not acquire any developmental milestones. Spastic quadriplegia can lead to severe contractures of the limbs and neurogenic scoliosis. Feeding difficulties (gastroesophageal reflux disease, frequent vomiting, swallowing dysfunction, and gastroesophageal incoordination) are a significant problem in most affected individuals. A majority have cortical blindness. MRI findings are nonspecific but may include generalized atrophy and simplified gyral pattern.
Common variable immunodeficiency-10 is an autosomal dominant primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency (summary by Chen et al., 2013). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Combined oxidative phosphorylation deficiency-18 is an autosomal recessive disorder of mitochondrial function characterized by intrauterine growth retardation, hypotonia, visual impairment, speech delay, and lactic acidosis associated with decreased mitochondrial respiratory chain activity. Affected patients may also show hematologic abnormalities, mainly macrocytic anemia (summary by Hildick-Smith et al., 2013). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Verheij syndrome is characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. Additional variable features may include coloboma, renal defects, and cardiac defects (summary by Verheij et al., 2009 and Dauber et al., 2013).
Immunodeficiency-15B (IMD15B) is an autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T cells. However, functional studies show impaired differentiation and activation of immune cells (summary by Pannicke et al., 2013).
Immunodeficiency-16 is an autosomal recessive primary immunodeficiency associated with classic Kaposi sarcoma of childhood and poor T-cell recall immune responses due to complete functional OX40 deficiency (Byun et al., 2013).
A form of congenital disorders of N-linked glycosylation with characteristics of developmental delay, intellectual disability, failure to thrive, hypotonia and seizures. Caused by mutations in the gene STT3A (11q23.3).
Nagashima-type palmoplantar keratoderma is an autosomal recessive nonsyndromic diffuse palmoplantar keratosis, first described by Nagashima (1977) in the Japanese literature. It is characterized by well-demarcated diffuse erythematous hyperkeratosis that extends onto the dorsal surfaces of the palms and feet and the Achilles tendon area. Involvement of the elbows and knees has also been reported, and there is a high frequency of hyperhidrosis on the palms and soles. In contrast to other types of transgressive diffuse hyperkeratosis such as mal de Meleda (248300) and the Gamborg Nielsen type of recessive PPK (PPK Norrbotten; 244850), PPKN shows only mild hyperkeratosis that is nonprogressive after the second decade and does not involve flexion contractures or constricting bands (summary by Kubo et al., 2013). For a discussion of phenotypic and genetic heterogeneity of palmoplantar keratoderma, see epidermolytic PPK (144200).
Immunodeficiency-17 is an autosomal recessive primary immunodeficiency characterized by highly variable clinical severity. Some patients have onset of severe recurrent infections in early infancy that may be lethal, whereas others may be only mildly affected or essentially asymptomatic into young adulthood. More severely affected patients may have evidence of autoimmune disease or enteropathy. The immunologic pattern is similar among patients, showing partial T-cell lymphopenia, particularly of cytotoxic CD8 (see 186910)-positive cells, decreased amounts of the CD3 complex, and impaired proliferative responses to T-cell receptor (TCR)-dependent stimuli. B cells, natural killer (NK) cells, and immunoglobulins are usually normal. Although thymic output of functional naive T cells early in life is decreased, polyclonal expansion of functional memory T cells is substantial. The phenotype in some patients is reminiscent of severe combined immunodeficiency (SCID) (summary by Timon et al. (1993) and Recio et al. (2007)).
Immunodeficiency-18 is an autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18 (summary by de Saint Basile et al., 2004).
Arrhythmogenic right ventricular cardiomyopathy/dysplasia is characterized by progressive fibrofatty myocardial replacement, primarily of the right ventricle. The main clinical features are structural and functional abnormalities of the ventricles, electrocardiographic depolarization/repolarization changes, reentrant arrhythmias, and sudden death (summary by van Hengel et al., 2013).
Immunodeficiency-19 (IMD19) is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by onset in early infancy of recurrent bacterial, viral, and fungal infections. Patients usually have chronic diarrhea, recurrent respiratory infections, and failure to thrive. Immunologic work-up shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype. The disorder is lethal in early childhood without bone marrow transplantation (summary by Yu et al., 2011).
Carcinomas of the biliary tract are aggressive malignancies, with 5-year survival of less than 10%. These carcinomas arise throughout the biliary tree and are anatomically classified as either intrahepatic or extrahepatic cholangiocarcinomas. Gallbladder carcinomas also arise from the biliary tree but have distinct natural histories compared to cholangiocarcinomas, suggesting different underlying tumor biology. Cholangiocarcinoma incidence varies widely between geographic regions, reflecting the impact of different underlying etiologies. In endemic areas, liver fluke infections by O. viverrini and Clonorchis sinensis, both group I carcinogens, represent the major risk factor for cholangiocarcinomas. In nonendemic regions, other risk factors, including choledochal cysts (603003), hepatolithiasis, and primary sclerosing cholangitis (613806), are likely contributors (summary by Chan-on et al., 2013). Overall, the majority of patients lack such identifiable risk factors (summary by Jiao et al., 2013).
Hereditary spastic paraplegia-72 is a pure form of spastic paraplegia with onset of difficulty walking and stiff legs associated with hyperreflexia and extensor plantar responses in early childhood. The disorder is slowly progressive, and some patients develop the need for assistance in walking. Some patients may have pes cavus or sphincter disturbances. Cognition, speech, and ocular function are normal (summary by Esteves et al., 2014). For a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600), and for autosomal recessive spastic paraplegia, see SPG5A (270800).
Autosomal dominant deafness-56 is a form of nonsyndromic sensorineural hearing loss. Hearing impairment shows postlingual onset and is progressive (summary by Zhao et al., 2013).
Hereditary sensory neuropathy type IF is an autosomal dominant sensory neuropathy affecting the lower limbs. Distal sensory impairment becomes apparent during the second or third decade of life, resulting in painless ulceration of the feet with poor healing, which can progress to osteomyelitis, bone destruction, and amputation. There is no autonomic involvement, spasticity, or cognitive impairment (summary by Kornak et al., 2014). For a discussion of genetic heterogeneity of HSN, see HSAN1A (162400).
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500).
Increased length of the superior cerebellar peduncle. [HPO:probinson]
Neurodegeneration with brain iron accumulation refers to a group of neurodegenerative disorders characterized by progressive motor and cognitive dysfunction beginning in childhood or young adulthood. Patients show extrapyramidal motor signs, such as spasticity, dystonia, and parkinsonism. Brain imaging shows iron accumulation in the basal ganglia (summary by Dusi et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (234200).
CLCN2-related leukoencephalopathy (CC2L) is characterized by nonspecific neurologic findings, mild visual impairment from chorioretinopathy or optic atrophy, male infertility, and characteristic findings on brain MRI. Neurologic findings include mild ataxia (action tremor and gait instability following initially normal motor development; occasionally mild spasticity), learning disabilities in some (ranging from mild to severe cognitive impairment), and headaches in some (usually intermittent, severe, and diffuse). Affected individuals remain ambulatory and do not require support for walking, and none has become blind. To date CC2L has been reported or identified in 16 individuals from 15 families. It is not yet known if the findings occurring in single individuals (i.e., vertigo, tinnitus, and progressive hearing loss; psychiatric symptoms; and paroxysmal kinesigenic dyskinesia) are part of the phenotypic spectrum or unrelated findings.
Myopathy with extrapyramidal signs is an autosomal recessive disorder characterized by early childhood onset of proximal muscle weakness and learning disabilities. While the muscle weakness is static, most patients develop progressive extrapyramidal signs that may become disabling (summary by Logan et al., 2014).
Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is characterized by the skin findings of poikiloderma (typically beginning in the first six months and mainly localized to the face), hypohidrosis with heat intolerance, mild lymphedema of the extremities, chronic erythematous and scaly skin lesions on the extremities, sclerosis of the digits, and mild palmoplantar keratoderma. Scalp hair, eyelashes, and/or eyebrows are typically sparse. Muscle contractures are usually seen in childhood and can be present as early as age two years. The majority of affected individuals develop progressive weakness of the proximal and distal muscles of all four limbs. Some adults develop progressive interstitial pulmonary fibrosis, which can be life-threatening within three to four years after respiratory symptoms appear. Other features are exocrine pancreatic insufficiency, liver impairment, hematologic abnormalities, relative short stature, and cataract.
Auriculocondylar syndrome (ARCND) is a rare craniofacial disorder involving first and second pharyngeal arch derivatives and includes the key features of micrognathia, temporomandibular joint and condyle anomalies, microstomia, prominent cheeks, and question mark ears (QMEs). QMEs consist of a defect between the lobe and the upper two-thirds of the pinna, ranging from a mild indentation in the helix to a complete cleft between the lobe and helix (summary by Gordon et al., 2013). For a general phenotypic description and discussion of genetic heterogeneity of auriculocondylar syndrome, see ARCND1 (602483).
Immunodeficiency-20 is a rare autosomal recessive primary immunodeficiency characterized by functional deficiency of NK cells. Patient NK cells are defective in spontaneous cell cytotoxicity, but retain antibody-dependent cellular cytotoxicity. Patients typically present early in childhood with severe herpes viral infections, particularly Epstein Barr virus (EBV), and human papillomavirus (HPV) (summary by Grier et al., 2012).
Bone marrow failure syndrome-2 is an autosomal recessive disorder characterized by trilineage bone marrow failure, learning disabilities, and microcephaly. Cutaneous features and increased chromosome breakage are not features (Tummala et al., 2014). For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675).
Hyperphosphatasia with mental retardation syndrome-4 is an autosomal recessive neurologic disorder characterized by severely delayed psychomotor development, mental retardation, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase (summary by Howard et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (239300). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Renal hypodysplasia/aplasia belongs to a group of perinatally lethal renal diseases, including bilateral renal aplasia, unilateral renal agenesis with contralateral dysplasia (URA/RD), and severe obstructive uropathy. Renal aplasia falls at the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT; 610805), and usually results in death in utero or in the perinatal period. Families have been documented in which bilateral renal agenesis or aplasia coexists with unilateral renal aplasia, renal dysplasia, or renal aplasia with renal dysplasia, suggesting that these conditions may belong to a pathogenic continuum or phenotypic spectrum (summary by Joss et al., 2003; Humbert et al., 2014). For a discussion of genetic heterogeneity of renal hypodysplasia/aplasia, see RHDA1 (191830).
Bosch-Boonstra-Schaaf optic atrophy syndrome is an autosomal dominant disorder characterized by delayed development, moderate intellectual disability, and optic atrophy. Most patients also have evidence of cerebral visual impairment. Dysmorphic facial features are variable and nonspecific (summary by Bosch et al., 2014).
Visual impairment due to central nervous system dysfunction.
Premature ovarian failure (POF), the endpoint of primary ovarian insufficiency, affects approximately 1% of women worldwide. Patients with POF present with at least a 6-month history of amenorrhea and elevated plasma levels of follicle-stimulating hormone (more than 40 mIU per milliliter). The disorder can result from premature depletion of the follicle pool, follicular atresia, follicle growth arrest, or ovarian dysgenesis (see 233300). In approximately 10 to 15% of patients with POF, a genetic cause has been determined (summary by Caburet et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360).
Nonsyndromic primary ovarian insufficiency, which is characterized by amenorrhea with elevated gonadotropin levels, is observed in 1% of otherwise healthy women under the age of 40 years (summary by Wang et al., 2014). For a general phenotypic description and discussion of the genetic heterogeneity of premature ovarian failure, see POF1 (311360).
An autosomal dominant form of early infantile epileptic encephalopathy, caused by mutation(s) in the GABRA1 gene, encoding gamma-aminobutyric acid receptor subunit alpha-1.
Atrial standstill (AS) is a rare condition characterized by the absence of electrical and mechanical activity in the atria. On surface ECG, AS is distinguished by bradycardia, junctional (usually narrow complex) escape rhythm, and absence of the P wave. Nearly 50% of patients with AS experience syncope. AS can be persistent or transient, and diffuse or partial (summary by Fazelifar et al., 2005).
Moyamoya disease-6 is a progressive vasculopathy characterized by occlusion of the terminal portion of the internal carotid arteries and its branches, and the formation of compensatory neovascularization and the moyamoya, or 'puff of smoke,' appearance of these vessels on angiogram. Affected individuals may present with ischemic strokes, intracerebral hemorrhage, or transient ischemic attacks. Patients with MYMY6 usually present early in life with achalasia. Hypertension and Raynaud phenomenon may be associated features (summary by Wallace et al., 2016; Herve et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of moyamoya disease, see MYMY1 (252350).
The four children with carbonic anhydrase VA (CA-VA) deficiency reported to date presented between day two of life and age 20 months with hyperammonemic encephalopathy (i.e., lethargy, feeding intolerance, weight loss, tachypnea, seizures, and coma). Data on long-term follow up are limited (the oldest known patient is age 7 years). Two of the four children showed normal psychomotor development and two showed mild learning difficulties and delayed motor skills. Seven additional children diagnosed with CA-VA deficiency (but not yet published) presented similarly.
Autosomal recessive bilateral perisylvian polymicrogyria is characterized by strikingly restricted polymicrogyria limited to the cortex surrounding the Sylvian fissure. Affected individuals have intellectual and language difficulty and seizures, but no motor disability (Bae et al., 2014).
A form of sensorineural hearing impairment that affects primarily the lower frequencies.
A increased anteroposterior thickness of the cornea.
A pterygium (or pterygia) in the intercrural (groin) region.
Neurofibromas present in a smaller number than usually seen in neurofibromatosis type 1.
An increased level of hypoxanthine in the urine.
A form of drug hypersensitivity syndrome caused by anti-convulsants.
A class of drugs that stimulate chloride ion influx through cell membrane channels.
The absence of rearrangement of at least one allele of the T-cell receptor gamma gene locus. This lack of rearrangement is characteristic of early thymocyte precursors and a lack of V(D)J recombination. This genetic profile is a predictor of induction therapy failure in children with T-cell acute lymphoblastic leukemia.
A malignant epithelial neoplasm arising from basal cells. (SEND)
A dimethane sulfonate derivative and alkylating agent with a structure similar to other alkylating agents such as chlorambucil, busulfan and melphalan, with potential antineoplastic activity. Although the exact mechanism of action has yet to be fully elucidated, benzaldehyde dimethane sulfonate alkylates DNA, which results in DNA double strand breaks, inhibition of DNA replication, cell cycle arrest and cell death. In addition, this agent is metabolized by the enzyme aldehyde dehydrogenase (ALDH) into the active carboxylic acid metabolite benzoic acid dimethane sulfonate (BA), which further contributes to its alkylating activity. Unlike other alkylating agents, benzaldehyde dimethane sulfonate has demonstrated antitumor activity in renal cell carcinoma.
An electrocardiographic finding of intermittent failure of atrial electrical impulse conduction to the ventricles, characterized by a progressively lengthening PR interval prior to the block of an atrial impulse. (CDISC)
An electrocardiographic finding of intermittent failure of atrial electrical impulse conduction to the ventricles, characterized by a relatively constant PR interval prior to the block of an atrial impulse.
An electrocardiographic finding of abnormally slow heart rate. Thresholds for different age, gender, and patient populations exist.
A change in the valine at position 600 of the serine/threonine-protein kinase B-raf protein to another amino acid.
A clinical finding that refers to the spread of a neoplastic disease to anatomic sites or systems other than the original neoplastic site through the detection of low or subclinical levels of a neoplastic marker.
A ventricular tachyarrhythmia characterized by a high ventricular rate (180 and 250 beats per minute) with a regular rhythm. The electrocardiogram shows large oscillating sine wave-like complexes occurring as a result of QRS complexes and T waves being merged. The P wave is not visible.
Prior to the development of ROP in the premature infant, vascularization of the retina is incomplete or immature. In Stage 0, there is no clear demarcation line between vascularized and non-vascularized retina.
A skin hypersensitivity reaction due to exposure to a pharmacologic substance that is characterized by raised purpuric lesions, red macules, hemorrhagic blisters and ulcerations.
Extravasation of blood into the subcutaneous space.
A response indicating that something happens or happened none of the time.
A response indicating that something happens or happened all of the time.
A breast carcinoma characterized by the formation of irregular, finger-like projections of fibrous stroma covered with neoplastic epithelial cells.
A benign neoplasm arising from the islet cells of the pancreas.
The oil extracted from the roots of Iris germanica, Iris florentina, and Iris pallida. Orris root oil is used as a perfume ingredient and as an ingredient in gin.
An aqueous solution composed of glucose and electrolytes, including sodium, potassium, chloride, magnesium, and phosphorus, with dehydration preventative and rehydration activities. Upon oral administration of the oral rehydration solution (ORS), water, electrolytes and glucose are absorbed from the gastrointestinal (GI) tract into the systemic circulation. This replenishes the body's supply of water, carbohydrates and electrolytes, and prevents both dehydration and renal dysfunction.
Labor in a woman who has had one or more previous cesarean births.
A liposomal formulation containing a nucleotide that mimics the human tumor suppressor microRNA (miRNA) miR-34, with potential antineoplastic activity. Upon administration, liposome-encapsulated MRX34 mimics miR-34 by inhibiting the expression of a variety of oncogenes including MYC, MET, BCL2, and beta-catenin. This induces cell cycle arrest, senescence and apoptosis in susceptible tumor cells. miR-34 is downregulated in most solid and hematologic malignancies and regulates the expression of a variety of genes. This miRNA plays an important role in the inhibition of cancer cell stemness, metastasis and cancer cell survival.
Effortless regurgitation of gastric contents that commonly occurs in infants, usually right after feeding or burping.
Birth at 39 weeks and 0 days through 40 weeks and 6 days.
A circumscribed, fluid-containing, epidermal elevation generally considered less than 10mm in diameter at the widest point.
Unexpected death of an infant less than one year of age, whose cause of death is not immediately obvious prior to investigation.
An electrocardiographic finding of a junctional rhythm with a heart rate which is abnormally elevated. (CDISC)
A phosphaturic mesenchymal tumor with benign histologic features. It may recur locally but does not metastasize. Complete excision is curative.
A longstanding lesion caused by death of tissue due to external pressure.
A traditional Chinese medicine comprising of Radix Angelicae Sinensis (RAS) and Radix Astragali (RA), with potential anti-inflammatory, immunostimulatory, neuroprotective, anti-hepatotoxic and antineoplastic activities. The main chemical constituents of RAS include ferulic acid, Z-ligustilide, butylidenephthalide and various polysaccharides. RA is the dried root of Astragalus membranaceus with primary constituents such polysaccharides, triterpenoids as well as isoflavones. Though their mechanisms of action remain largely elusive, Radix Angelicae Sinensis/Radix Astragali herbal supplements are commonly used for the treatment of various health conditions affecting women including premenstrual syndrome, dysmenorrhea, pelvic pain, recovery from childbirth and menopausal symptoms. These agents are also used for alleviating constipation, preventing and treating anemia and allergic attacks, and for the management of hypertension, joint pain and ulcers.
A third-generation, supramolecular platinum-based compound composed of carboplatin linked, by a strong hydrogen bond, to 1,1-cyclobutane dicarboxylate (CBDCA), with potential antineoplastic activity. Although the exact mechanism of action has yet to be fully elucidated, dicycloplatin appears to have a mechanism of action similar to that of other platinum-based compounds, which involves both DNA binding and the formation of DNA crosslinks. This mechanism results in the induction of apoptosis and cell growth inhibition. Compared to carboplatin alone, dicycloplatin shows enhanced solubility and stability in aqueous solution and appears to have a more favorable toxicity profile.
An allogeneic renal cell cancer (RCC) vaccine composed of cell line-derived RCCs that are genetically engineered to express the murine alpha-1,3-galactosyltransferase (GalT), with potential immunostimulatory and antineoplastic activities. Not naturally occurring in humans, GalT catalyzes the expression of foreign alpha-1,3-galactosyl (alpha-gal) carbohydrate epitopes on the cell membranes of the allogeneic RCCs present in the vaccine. This induces a hyperacute rejection reaction involving pre-existing human anti-alpha-gal antibodies, which bind to the foreign alpha-gal epitopes expressed by the allogeneic RCCs. This results in complement-mediated cytotoxicity (CMC) and antibody-dependent cell-mediated cytotoxicity (ADCC) towards endogenous RCCs with unmodified carbohydrate epitopes.
An electrocardiographic finding of a tachycardia which does not originate in the ventricles or His Purkinje system. There is an abnormally high heart rate and QRS complexes are typically narrow, but aberration or preexcitation may be present. (CDISC)
An electrocardiographic finding of two sinus beats followed by a premature ventricular complex for 3 or more consecutive cycles; a regularly irregular rhythm of normal and abnormal QRS complexes in a 2-1 ratio. (CDISC)
A status indication that a subject is already assigned to an arm of a clinical trial by chance.
A finding referring to a medical device that is no longer held or possessed; incapable of being recovered or regained.
A benign germ-cell neoplasm derived from pluripotent cells and consisting of components from one or more of the three germ-cell layers.
A cell lysate derived from sarcoma cells with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the autologous sarcoma cell lysate exposes the immune system to an undefined amount of sarcoma-type tumor associated antigens (TAA), which may result in the induction of both specific anti-tumoral cytotoxic T lymphocytes (CTL) and antibody-dependent responses against the sarcoma TAA-expressing cells, resulting in sarcoma cell lysis.
A cell lysate derived from glioma cells with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the autologous glioma cell lysate exposes the immune system to an undefined amount of glioma-type tumor associated antigens (TAA), which may result in the induction of both specific anti-tumoral cytotoxic T lymphocytes (CTL) and antibody-dependent responses against the glioma TAA-expressing cells, resulting in glioma cell lysis.
A malignant neoplasm composed of a mixed lymphocyte population.
A benign neoplasm of the thymus, originating from epithelial thymus cells.
A benign epithelial neoplasm with a uniform, monomorphic appearance that is dominated by basal cells. (SEND)
Absence of detectable signs or symptoms.
An orally available inhibitor of the receptor tyrosine kinase activity of anaplastic lymphoma kinase (ALK) with antineoplastic activity. Upon administration, ceritinib binds to and inhibits wild-type ALK kinase, ALK fusion proteins and ALK point mutation variants. Inhibition of ALK leads to both the disruption of ALK-mediated signaling and the inhibition of cell growth in ALK-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. ALK dysregulation and gene rearrangements are associated with a variety of tumor cell types.
Corticotropin (39 aa, ~5 kDa) is encoded by the human POMC gene. This protein plays a role in the stimulation of cortisol secretion by the adrenal gland.
A radioconjugate composed of a fluorinated pyrimidine analog, linked to the radioisotope fluorine F 18 with potential imaging activity using positron emission tomography/computed tomography (PET/CT). Upon administration of fluorine F 18 5-fluoro-2-deoxycytidine ([F-18]-FdCyd), the FdCyd moiety is phosphorylated by deoxycytidine kinase to 5-fluoro-2'-deoxycytidylate (FdCMP) and deaminated by deoxycytidylate (dCMP) deaminase, an enzyme overexpressed by tumor cells, to 5-fluoro-2-deoxyuridine monophosphate (FdUMP). Eventually, FdUMP is metabolized to the triphosphate forms 5-fluoro-2'-deoxycytidine-triphosphate (FdCTP) and fluorodeoxyuridine triphosphate (FdUTP). FdCTP and FdUTP inhibit DNA methyltransferase (DNMT) and DNA methylation, and induce DNA strand breaks, respectively. FdCyd is coadministered with tetrahydrouridine (THU), an inhibitor of cytidine/deoxycytidine deaminase, which prevents FdCyd breakdown and increases its efficacy. The fluorine F 18 moiety can be imaged upon PET/CT, thereby allowing for the evaluation of the biodistribution of FdCyd and its uptake by tumor cells.
A long-acting release (LAR) formulation containing pasireotide, a synthetic long-acting cyclohexapeptide, with somatostatin-like activity. Upon intramuscular administration of the LAR formulation of pasireotide, this somatostatin analog strongly binds to and activates somatostatin receptor (SSTR) subtypes 1, 2, 3, and 5. This leads to an inhibition in the secretion of human growth hormone (hGH) and results in decreased production of insulin-like growth factor (IGF-1), which may inhibit IGF-1-mediated cell signaling pathways. This may lead to an inhibition in tumor cell growth and an increase in apoptosis in IGF-1-overexpressing tumor cells. In addition, this agent causes a reduction in adrenocorticotropic hormone (ACTH), which leads to an inhibition of cortisol secretion. ACTH-producing tumors cause hypersecretion of cortisol which results in many unwanted symptoms. This agent may also block other key survival pathways such as the phosphatidylinositol 3-kinase (PI3K) and the mitogen-activated protein kinase (MAPK) signaling pathways. Pasireotide also inhibits vascular endothelial growth factor (VEGF) secretion, thereby decreasing angiogenesis and tumor cell growth in VEGF-overexpressing tumor cells. The long-acting form of pasireotide allows for less frequent administration as compared to the original form of this agent. SSTRs are overexpressed by some neuroendocrine and non-neuroendocrine tumor cells.
An intraductal papillary-mucinous neoplasm of the pancreas that arises in one of the branches of the main pancreatic duct. It usually has an indolent behavior.
An injectable formulation composed of opebacan, a 21 kDa recombinant fragment of human bactericidal/permeability-increasing protein (BPI), with potential anti-infective activity. Upon intravenous administration, opebacan is able to mimic BPI and binds to and neutralizes lipopolysaccharides (LPS or endotoxins), which are components of the cell wall of gram-negative bacteria that induce a potent innate immune response. This may prevent an endotoxin-mediated inflammatory response and may prevent graft-versus-host-disease (GvHD) after myeloablative allogeneic hematopoietic stem cell transplantation (aHSCT). BPI, a host-defense protein against microbial infection, is naturally produced by neutrophils. Chemo- and radio-therapy induce neutropenia and depletion of endogenous BPI. These therapies also cause intestinal damage and release of bacterial endotoxins into the bloodstream, which initiate a systemic inflammatory response, activate donor T-lymphocytes and possibly cause GvHD following aHSCT.
A term that refers to a pulmonary nodule in which part of the ground-glass opacity completely obscures the parenchyma on CT scan examination.
A morphologic finding indicating the presence of single cells or small groups of cells with prominent eosinophilic cytoplasmic granules in a tissue sample.
A lipid-based nanosomal formulation of the poorly soluble, semi-synthetic, second-generation taxane docetaxel, with potential antineoplastic activity. Upon intravenous injection, docetaxel binds to and stabilizes tubulin, which inhibits microtubule disassembly and results in both cell cycle arrest at the G2/M phase and cell death. This liposomal formulation solubilizes docetaxel without the use of toxic solvents, such as polysorbate 80. This permits the administration of larger doses of docetaxel and improves the drug's safety profile by avoiding solvent-associated toxicities, such as hypersensitivity reactions and neurotoxicity. In addition, the nanosomal lipid-based delivery of docetaxel improves drug penetration into tumors and decreases drug clearance, all of which prolong the duration of docetaxel's therapeutic effects.
An intraductal papillary-mucinous neoplasm of the pancreas that arises from the main pancreatic duct.
A bacteriochlorin-based photosensitizer, with antineoplastic activity upon photodynamic therapy (PDT). Following intravenous administration, the photosensitizer LUZ 11 preferentially accumulates in hyperproliferative tissues, such as tumors. Local application of laser light at the tumor site results in the absorption of light by this agent and a photodynamic reaction between LUZ 11 and oxygen. This results in the production of reactive oxygen species (ROS), which includes singlet oxygen molecules, the superoxide ion, and other cytotoxic free radicals. The formation of ROS induces free radical-mediated DNA damage and cell death.
A proprietary water- and lipid-soluble polymer-based nutritional supplement composed of a complex mixture of alpha-lipoic acid bound to palladium (Palladium Lipoic Acid Complex (PdLA)) and other minerals, vitamins and amino acids, including vitamins B1, B2 and B12, formylmethionine, acetyl cysteine, and trace amounts of molybdinum, rhodium, and ruthenium, with potential anti-oxidant and cytoprotective activities. Upon oral administration, the alpha-lipoic acid-palladium/vitamin/mineral supplement acts as a free radical scavenger, crosses the cell membrane and is able to transfer electrons from fatty acids to DNA via the electron transport chain in mitochondria, which protects against DNA damage. This could protect non-cancerous cells from the oxidative damage caused by radiation and chemotherapy. In addition, in the hypoxic conditions found within tumors, the excess electrons can generate free radicals within mitochondria and could induce both cytochrome c release and apoptosis.
The potassium salt form of heparin, a sulfur-rich glycosaminoglycan with anticoagulant activity. Heparin binds to antithrombin III to form a heparin-antithrombin III complex. The complex binds to and inactivates thrombin (factor IIa) and other activated clotting factors, such as factors IXa, Xa, XIa, and XIIa. The inactivation of thrombin prevents the polymerization of fibrinogen to fibrin and the subsequent formation of blood clots.
A rare type of juvenile idiopathic inflammatory myopathy with onset before 18 years of age of chronic skeletal muscle inflammation, manifesting as progressive, proximal and distal muscle weakness and atrophy.
An antibody-drug conjugate (ADC) consisting of an afucosylated, humanized monoclonal antibody, directed against the B-cell maturation antigen (BCMA), conjugated to the auristatin analogue and microtubule inhibitor monomethyl auristatin phenylalanine (MMAF), with potential antineoplastic activity. The anti-BCMA antibody moiety of anti-BCMA ADC GSK2857916 selectively binds to the BCMA on tumor cell surfaces. Upon internalization, the MMAF moiety binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces tumor cell apoptosis. In addition, GSK2857916 induces antibody-dependent cellular cytotoxicity (ADCC). Altogether, this results in the inhibition of cellular proliferation in tumor cells that overexpress BCMA. BCMA, a receptor for a proliferation-inducing ligand and B-cell activating factor, is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a key role in plasma survival; it is found on the surfaces of plasma cells and overexpressed on malignant plasma cells. Afucosylation of the antibody moiety increases ADCC.
A small molecule radiopharmaceutical composed of the radioisotope iodine I 124 covalently attached to a proprietary alkylphospholipid ether (PLE) analogue, with potential imaging activity upon positron emission tomography (PET). Iodine I 124 phospholipid ether analogue CLR1404 is selectively taken up by tumor cells via membrane lipid rafts and accumulates in tumor cells. The accummulation of this agent is due to a decreased ability of tumor cells to metabolize PLEs because certain tumor cells have lower levels of the enzyme phospholipase-D, in comparison to normal cells. This facilitates imaging of cancer cells by PET. Lipid rafts, specialized microdomains of plasma membrane, are overexpressed in cancer cells compared to normal cells. In addition, the radioiodine moiety of this agent is resistant to de-iodination.
A preparation of allogeneic neural stem cells (NSC), derived from a human fetal cell line, that are adenovirally-transduced to express a modified form of the human enzyme carboxylesterase (CE) hCE1m6, with potential adjuvant activity. Upon intracranial administration, NSCs localize to tumor sites, due to their tumor-trophic nature, and transiently express hCE1m6. Intravenous co-administration of the prodrug irinotecan allows for the selective conversion by hCE1m6 to its active metabolite and topoisomerase I inhibitor, SN-38, in the vicinity of tumor sites. This leads to a local anti-neoplastic effect and causes reduced toxicity and increased therapeutic efficacy of irinotecan. Since NSCs freely cross the blood-brain barrier, these cells can also be intravenously administered to target brain tumor cells. hCE1m6 shows increased activity as compared to unmodified human CE.
A synthetic lipid A derivative and selective toll-like receptor 4 (TLR4) agonist composed of glucopyranosyl lipid-A (GLA) in a stable, oil-in-water emulsion (GLA-SE), with potential immunostimulating and antineoplastic activities. Upon intratumoral administration into the immunosuppressed tumor microenvironment (TME), TLR4 agonist G100 binds to and activates TLR4 on various immune cells, thereby stimulating dendritic cells (DCs), monocytes and macrophages. This activation results in the production of pro-inflammatory cytokines and chemokines. This induces a T helper cell-1 (Th1) immune response and activates a cytotoxic T-lymphocyte (CTL) response against tumor-associated antigens (TAAs) that were released in the TME by tumor cells lysed during cytotoxic treatments, such as radiotherapy. TLR4, a member of the TLR family, plays a key role in the activation of innate immunity.
A CT scan finding in the lungs indicating the presence of hazy areas of attenuation in the air spaces. It is caused by interstitial fibrosis, alveolar collapse, edema, inflammation, or cancer with lepidic spread.
A radioconjugate containing a derivative of the androgen testosterone, 16-beta-fluoro-5-alpha-dihydrotestosterone (FDHT), labeled with the radioisotope fluorine F18 (18F-FDHT), with potential use as an imaging agent for positron emission tomography (PET). Upon administration, 18F-FDHT binds to the androgen receptor (AR). Upon PET imaging, AR-expressing prostate tumor cells can be imaged and assessed.
A plasmid DNA encoding for the A fragment of Diphtheria Toxin (DTA) under the control of the H19 gene promoter (BC-819 or DTA-H19) and mixed with the transfectant polyethylenimine (PEI), with potential antineoplastic activity. Upon administration, the PEI moiety enhances the entry of the agent into rapidly dividing cells. Upon cell entry, activation of the H19 gene promoter-containing plasmids and DTA expression are limited to tumor cells, as high levels of H19 expression are only found in tumor cells. DTA disrupts protein synthesis. Tumor-cell selective expression of this toxin leads to the selective destruction of the tumor while sparing healthy, normal cells. H19, an oncofetal, regulatory RNA, is overexpressed in certain cancer cells while its expression in normal cells is minimal or absent; it plays a key role in cancer progression, angiogenesis and metastasis.
Autologous dendritic cells (DCs) transduced with a recombinant, replication-defective adenoviral vector expressing the fusion gene granulocyte-macrophage colony-stimulating factor (GM-CSF) and carbonic anhydrase IX (CA-IX or CA9) (GMCA-9), with potential immunomodulating activity. The autologous DCs are transduced ex vivo and express the GMCA-9 fusion protein on the cell surface. Upon intradermal administration of the AdGMCAIX-transduced autologous DCs back into the patient, the DCs activate the immune system to both mount a cytotoxic T lymphocyte-mediated response against tumor cells positive for the CA9 antigen, and generate memory T cells. This may result in decreased tumor growth. CA9, also known as G250, is a renal cell carcinoma (RCC)-associated antigen and a member of the carbonic anhydrase family that contains a human leukocyte antigen (HLA)-A2.1-restricted epitope; it is found in a majority of renal cell carcinomas while absent in most normal tissues. The cytokine GM-CSF enhances the immunogenicity of CA9-based DC vaccines.
A preparation of cells, which consists of autologous marrow infiltrating lymphocytes (MILs), that are manipulated in vitro, with potential antitumor and immune stimulating activities. MILs are harvested from autologous bone marrow from multiple myeloma patients and, in vitro, are exposed to and activated by anti-CD3/anti-CD28 monoclonal antibodies covalently attached to super-paramagnetic microbeads. After removal of the beads and expansion of the cells in culture, the activated MILs (aMILs) are re-introduced into the patient. The aMILs possess enhanced myeloma specificity, and are able to infiltrate the tumor microenvironment and initiate tumor cell lysis. CD3 and CD28, co-stimulatory molecules expressed on the surface of T-lymphocytes, play a key role in the activation of T-cells.
The hydrochloride salt form of anlotinib, a receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic and anti-angiogenic activities. Upon administration, anlotininib targets multiple RTKs, including vascular endothelial growth factor receptor type 2 (VEGFR2) and type 3 (VEGFR3). This agent may both inhibit angiogenesis and halt tumor cell growth.
A conjugate containing the antimetabolite and antifolate agent methotrexate conjugated to insulin-like growth factor (IGF), with potential antineoplastic activity. After intravenous administration, the IGF moiety of the IGF-methotrexate conjugate binds to and is internalized by IGF receptors (IGFR) on the surface of tumor cells. Following cell entry, the methotrexate then binds to and inhibits the enzyme dihydrofolate reductase, which catalyzes the conversion of dihydrofolate to tetrahydrofolate. This results in both the inhibition of DNA and RNA synthesis and the induction of death in rapidly dividing cells. Binding to IGFR can localize the cytotoxic effect of methotrexate in tumor cells. This may increase its efficacy while decreasing its toxicity to normal, healthy cells. IGFR is overexpressed on many types of cancer cells and has been implicated in metastasis and resistance to apoptosis.
A radioconjugate consisting of a lipophilic, bioreductive copper(II)bis(thiosemicarbazone) complex, copper-pyruvaldehyde-bis(N4-methylthiosemicarbazone) (Cu-PTSM), linked to the beta-emitting, radioisotope copper Cu 62, with potential perfusion and positron emitting tomography (PET) tumor imaging activities. Upon injection, the distribution of copper Cu 62-PTSM correlates with blood flow. This agent's high membrane permeability allows for rapid diffusion into cells. Once it enters the cell, 62Cu-PTSM is then reduced by the mitochondria, which prevents diffusion of the agent out of the cell. Upon PET imaging, tumor blood flow can be visualized and tumor perfusion can be assessed. Compared with other copper radionuclides, the short half-life of copper Cu 62 (9.7 minutes) reduces the amount of radiation a patient is subjected to and allows for several imaging studies to be performed. PTSM lacks selectivity for hypoxic cells.
A radioconjugate consisting of a lipophilic, neutral, bioreductive copper-bis(thiosemicarbazone) complex, copper-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM), labeled with the beta-emitting radioisotope copper Cu 62, with hypoxia-selective and positron emitting tomography (PET) radioimaging activities. With a high membrane permeability and low reduction potential, copper Cu 62-ATSM easily enters cells. This agent can only be reduced by mitochondria found in hypoxic cells with abnormally high electron concentrations. This chemical reaction traps Cu 62-ATSM in the cell, which allows for the selective accumulation of this agent in hypoxic cells compared to normoxic cells. The extent of copper Cu 62-ATSM retention in tissue is inversely related to the state of tissue oxygenation allowing the quantitation of tissue hypoxia with PET. This provides information about diagnosis, prognosis, treatment options and outcomes for certain cancers. The short half-life of copper Cu 62 (9.7 minutes) reduces the amount of radiation a patient is subjected to and allows for several imaging studies to be performed. Hypoxic tumors are associated with increased malignancy and resistance to radiation and chemotherapy.
A therapeutic preparation consisting of the beta-emitting radioisotope rhenium Re 186 encapsulated in a nanoliposome, with potential antineoplastic activity. Upon intratumoral infusion of liposomal rhenium Re 186, the radioisotope releases radiation, which directly kills the tumor cells. The nanoliposomes facilitate the retention of the radioisotope by the tumor cells and localize the radiocytotoxicity to the tumor while sparing surrounding normal, healthy cells. Re-186 has a short half-life and a short path length, which contributes further to limiting the radiotoxicity to the tumor cells.
A small molecule inhibitor of the BET (Bromodomain and Extra-Terminal) family of bromodomain-containing proteins with potential antineoplastic activity. Upon administration, the BET inhibitor RO6870810 binds to the acetylated lysine recognition motifs found in the bromodomain of BET proteins, which prevents the interaction between BET proteins and acetylated histones. This interaction disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth. Characterized by a tandem repeat of bromodomains at the N-terminus, BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during cellular development and growth.
An orally active, highly selective, small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Upon administration, PI3K delta/gamma inhibitor RP6530 inhibits the PI3K delta and gamma isoforms and prevents the activation of the PI3K/AKT-mediated signaling pathway. This may lead to a reduction in cellular proliferation in PI3K delta/gamma-expressing tumor cells. In addition, this agent modulates inflammatory responses through various mechanisms, including the inhibition of both the release of reactive oxygen species (ROS) from neutrophils and tumor necrosis factor (TNF)-alpha activity. Unlike other isoforms of PI3K, the delta and gamma isoforms are overexpressed primarily in hematologic malignancies and in inflammatory and autoimmune diseases. By selectively targeting these isoforms, PI3K signaling in normal, non-neoplastic cells is minimally impacted or not affected at all, which minimizes the side effect profile for this agent.
An inhibitor of spleen tyrosine kinase (syk), with potential anti-inflammatory, immunomodulating, and antineoplastic activities. Spleen tyrosine kinase inhibitor TAK-659 may inhibit the activity of syk, which abrogates downstream B-cell receptor (BCR) signaling and leads to an inhibition of B-cell activation, chemotaxis, adhesion and proliferation. Syk, a BCR-associated non-receptor tyrosine kinase that mediates diverse cellular responses, including proliferation, differentiation, and phagocytosis, is expressed in hematopoietic tissues and is often overexpressed in hematopoietic malignancies.
An orally available small molecule and nucleoside antimetabolite with potential antineoplastic activity. Upon administration, the cytidine analog RX-3117 is taken up by cells through a carrier-mediated transporter, phosphorylated by uridine cytidine kinase (UCK) and then further phosphorylated to its diphosphate (RX-DP) and triphosphate forms (RX-TP). The triphosphate form is incorporated into RNA and inhibits RNA synthesis. The diphosphate RX-DP is reduced by ribonucleotide reductase (RR) to dRX-DP; its triphosphate form (dRX-TP) is incorporated into DNA. In addition, RX-3117 also inhibits DNA methyltransferase 1 (DNMT1). This eventually leads to cell cycle arrest and the induction of apoptosis. UCK is the rate-limiting enzyme in the pyrimidine-nucleotide salvage pathway.
A cancer vaccine composed of a heat-killed, recombinant form of the yeast Saccharomyces cerevisiae that is genetically modified to express the transcription factor brachyury protein, with potential antineoplastic activity. Upon subcutaneous administration, the brachyury-expressing yeast vaccine GI-6301 is recognized by dendritic cells, processed, and presented by Class I and II MHC molecules on the dendritic cell surface. This elicits a targeted CD4+ and CD8+ T-lymphocyte-mediated immune response. This process kills brachyury-expressing tumor cells. Brachyury is overexpressed in a variety of tumor types and plays an important role in cancer progression and metastasis.
An orally available inhibitor of extracellular signal-regulated kinase (ERK), with potential antineoplastic activity. Upon oral administration, GDC-0994 inhibits both ERK phosphorylation and activation of ERK-mediated signal transduction pathways. This prevents ERK-dependent tumor cell proliferation and survival. The mitogen-activated protein kinase (MAPK)/ERK pathway is upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation, differentiation and survival.
A novel histone deacetylase (HDAC) inhibitor with potential antineoplastic activity. Although the exact therapeutic mechanism of action for CXD101 is not known, oral administration of this agent should inhibit the catalytic activity of HDAC, which results in an accumulation of highly acetylated histones, followed by the induction of chromatin remodeling and an altered pattern of gene expression. HDAC, a family of enzymes upregulated in many tumor types, deacetylates chromatin-associated histone proteins.
A cancer vaccine composed of a combination of autologous glioblastoma (GBM) tumor cells, allogeneic GBM tumor cells, generated from three different GBM donor cancer patients, and the lysates of all of these cells, with potential antineoplastic activity. Upon intradermal administration of GBM cancer vaccine ERC1671, the mixture of the autologous and allogeneic cells and lysates stimulates the immune system to mount a cytotoxic T-lymphocyte (CTL) response against GBM-associated antigens, which leads to the destruction of glioblastoma cells.
An orally available MDM2 (murine double minute 2) antagonist with potential antineoplastic activity. Upon oral administration, MDM2 inhibitor DS-3032b binds to, and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this MDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This results in the restoration of p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger protein and a negative regulator of the p53 pathway, is overexpressed in cancer cells; it has been implicated in cancer cell proliferation and survival.
A phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor WX-037 specifically inhibits PI3K, which prevents the activation of the PI3K/protein kinase B-mediated signaling pathway. This may result in the inhibition of both tumor cell growth and survival in PI3K-overexpressing tumor cells. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis. Dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.
An oncolytic, replication-competent adenovirus encoding the human glycosylphosphatidylinositol-anchored enzyme PH20 hyaluronidase with potential antitumor activity. After intratumoral administration, PH20 hyaluronidase-expressing adenovirus VCN-01 selectively replicates in tumor cells, which may both cause oncolytic virus-induced cell death and induce the infection of adjacent tumor cells. In addition, the virus expresses hyaluronidase, which hydrolyzes and degrades the hyaluronic acid (HA) that coats tumor cells. The degradation of HA may result in a decrease for both the viscosity of the interstitial space and the tumor's interstitial fluid pressure (IFP). This increases viral spread and may result in the inhibition of tumor cell growth. In addition, HA degradation facilitates the penetration of chemotherapeutic agents into the tumor. HA is a glycosaminoglycan found in the extracellular matrix (ECM) and is frequently overproduced by various tumor cell types. The presence of HA in tumors correlates with increases in tumor cell growth, metastatic potential, tumor progression and resistance to chemotherapeutic agents.
An orally available inhibitor of both the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) and the tropomyosin-related kinases (TRK) TRKA, TRKB, and TRKC, with potential antineoplastic activity. Upon administration, ALK/TRK inhibitor TSR-011 binds to and inhibits both ALK and TRK kinases. The inhibition leads to disruption of ALK- and TRK-mediated signaling and impedes tumor cell growth in ALK/TRK-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. TRK, a family of receptor tyrosine kinases activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.
A water soluble, orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) and extracellular signal-regulated kinase (ERK), with potential antineoplastic activity. Upon administration, Akt/ERK inhibitor ONC201 binds to and inhibits the activity of Akt and ERK, which may result in inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathway as well as the mitogen-activated protein kinase (MAPK)/ERK-mediated pathway. This may lead to the induction of tumor cell apoptosis mediated by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/TRAIL death receptor type 5 (DR5) signaling in AKT/ERK-overexpressing tumor cells. The PI3K/Akt signaling pathway and MAPK/ERK pathway are upregulated in a variety of tumor cell types and play a key role in tumor cell proliferation, differentiation and survival by inhibiting apoptosis. In addition, ONC201 is able to cross the blood-brain barrier.
An orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. FGFR inhibitor TAS-120 selectively and irreversibly binds to and inhibits FGFR, which may result in the inhibition of both the FGFR-mediated signal transduction pathway and tumor cell proliferation, and increased cell death in FGFR-overexpressing tumor cells. FGFR is a receptor tyrosine kinase essential to tumor cell proliferation, differentiation and survival and its expression is upregulated in many tumor cell types.
A synthetic, 5-amino acid peptide and Innate Defense Regulator (IDR), with immunomodulating, anti-inflammatory, anti-infective and anti-mucositis activities. Upon intravenous administration, SGX942 binds to the ZZ domain of sequestosome-1, also called p62, and activates regulatory signaling transduction pathways involved in the modulation of the innate immune system, such as those mediated by mitogen-activated protein kinase (MAPK) p38 and CCAAT-enhancer-binding protein. This agent promotes monocyte and macrophage recruitment to, and accelerates healing in damaged and infected tissue; it suppresses inflammation through the regulation of the expression of multiple cytokines. This agent may prevent or decrease chemo- or radiotherapy-induced mucositis as well as other types of infection. p62, an intracellular adaptor protein that functions downstream of certain signaling receptors, plays a key role in the activation of the innate immune system.
A systemic gene therapy anti-cancer agent composed of cationic liposomes, which encapsulates plasmid DNA encoding for the tumor suppressor gene RB94 and is complexed with anti-transferrin receptor single chain antibody fragment (TfRscFv), with potential antineoplastic activity. Upon systemic administration of liposome-encapsulated RB94 plasmid DNA gene therapy agent SGT-94, the TfRscFv portion of this agent selectively targets the tumor cells expressing transferrin receptors. TfRscFv binding to the transferrin receptor allows receptor-mediated endocytosis and transfection, followed by the expression of RB94 gene. This induces tumor cell apoptosis through an as of yet unknown pathway. RB94 is a modified, N-terminal truncated form of the full-length protein retinoblastoma gene RB110, and exerts enhanced antitumor activity. The transferrin receptor (TfR) functions in cellular iron uptake through its interaction with transferrin, and is overexpressed in a variety of tumor types.
An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the anti-solute carrier family 39 zinc transporter member 6 (SLC39A6; LIV-1; ZIP6) protein that is conjugated, via a protease-cleavable linker, to the cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration and internalization by LIV-1-positive tumor cells, anti-LIV-1 antibody-drug conjugate SGN-LIV1A undergoes enzymatic cleavage to release MMAE into the cytosol. In turn, MMAE binds to and inhibits tubulin polymerization, which may result in G2/M phase cell cycle arrest and apoptosis in LIV-1-expressing tumor cells. LIV-1, a member of the zinc transporter family, is expressed in several types of solid tumors and plays a key role in tumor cell progression and metastasis. The linkage system in SGN-LIV1A is highly stable in plasma, resulting in cytotoxic specificity against LIV-1-positive cells.
A sequence-selective pyrrolobenzodiazepine (PBD) dimer with potential antineoplastic activity. Following intravenous administration, DNA minor groove binding agent SG2000 preferentially and covalently binds to purine-GATC-pyrimidine sequences, with the imine/carbinolamine moieties of SG2000 binding to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links and inhibits both DNA replication and gene transcription, which lead to the inhibition of cell growth. With a preference for binding to purine-GATC-pyrimidine sequences, SG2000 adducts do not appear to be susceptible to p53-mediated DNA excision repair.
An orally available spiro-oxindole HDM2 (human double minute 2) antagonist with potential antineoplastic activity. Upon oral administration, the p53-HDM2 protein-protein interaction inhibitor MI-773 binds to HDM2, preventing the binding of the HDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this HDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored, which may result in the restoration of p53 signaling and lead to the p53-mediated induction of tumor cell apoptosis. HDM2, a zinc finger protein and a negative regulator of the p53 pathway, is often overexpressed in cancer cells. It has been implicated in cancer cell proliferation and survival.
An orally bioavailable small molecule inhibitor of phosphorylated-p68 RNA helicase (P-p68), with potential anti-proliferative and antineoplastic activity. Upon oral administration, P-p68 inhibitor RX-5902 may both inhibit the activity of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein and facilitate the induction of cyclin-dependent kinase inhibitor 1 (p21). This may prevent G2/M cell cycle progression and lead to growth inhibition in tumor cells. P-p68 is overexpressed in various types of solid tumors but absent in normal tissues, and plays a role in tumor progression and metastasis. p21 is a potent cyclin-dependent kinase inhibitor which regulates cell cycle progression and mediates both growth arrest and cellular senescence.
An orally bioavailable dual inhibitor of spleen tyrosine kinase (Syk) and Janus-associated kinases (JAK), with potential anti-inflammatory and antineoplastic activity. Upon oral administration, Syk-JAK inhibitor PRT062070 specifically binds to and inhibits the activity of Syk, JAK1, and JAK3 with preferential inhibition of JAK1 and JAK3-dependent cytokine-mediated signaling and functional responses. This negatively affects the downstream JAK-STAT (signal transducer and activator of transcription) pathway, and leads to both reduced inflammation in various animal models and enhanced antiproliferative activity towards non-Hodgkin's lymphoma (NHL) cell lines. Syk is a non-receptor cytoplasmic tyrosine kinase involved in signal transduction in cells of hematopoietic origin including B cells, macrophages, basophils and neutrophils. Abnormal function of Syk has been implicated in several hematopoietic malignancies including NHL and chronic lymphocytic leukemia (CLL). The JAK-STAT pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies.
A bivalent human papillomavirus (HPV) therapeutic vaccine containing recombinant inactivated adenylate cyclase (CyaA) from Bordetella pertussis carrying a sequence encoding the E7 antigen of both HPV16 and 18, with potential immunostimulatory and antiviral properties. Upon administration of bivalent HPV16/18 therapeutic cervical cancer vaccine, the expressed proteins may activate cell-mediated immunity and induce both cytotoxic CD8+ T cells and CD4+ helper T cells against the target antigens HPV16-E7 and HPV18-E7, which leads to HPV viral clearance. Adenylate cyclase is a virulence factor of Bordetella pertussis. Its ability to bind to CD11b-expressing dendritic cells and deliver antigens directly to the cytosol allows the activation and induction of T-cell immunity. CyaA may also induce a B cell response.
An orally bioavailable inhibitor of serine/threonine-protein kinase B-raf (BRAF) protein with potential antineoplastic activity. BRAF inhibitor PLX8394 appears to selectively bind to and inhibit the activity of both wild-type and mutated forms of BRAF, which may subsequently inhibit the proliferation of tumor cells which express mutated forms of BRAF. This inhibitor appears to be effective against tumors that express multiple mutated forms of the kinase and may be an effective therapeutic agent for tumors that are resistant to other BRAF inhibitor therapies that are specific for the BRAF V600E mutant. BRAF, a member of the raf family of serine/threonine protein kinases, plays a role in the regulation of MAP kinase/ERK signaling pathways, which may be constitutively activated due to BRAF gene mutations. Mutated forms of BRAF are associated with a number of neoplastic diseases.
An inhibitor of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFK-2/FBPase) isoform 3 (PFKFB3) and derivative of 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), with potential antineoplastic activity. Upon administration, PFKFB3 inhibitor PFK-158 binds to and inhibits the activity of PFKFB3, which leads to the inhibition of both the glycolytic pathway in and glucose uptake by cancer cells. This prevents the production of macromolecules and energy that causes the enhanced cellular proliferation in cancer cells as compared to that of normal, healthy cells. Depriving cancer cells of nutrients and energy leads to the inhibition of cancer cell growth. PFKFB3, an enzyme that catalyzes the conversion of fructose-6-phosphate to fructose-2,6-bisphosphate, is highly expressed and active in human cancer cells; it plays a key role in increasing both glycolytic flux in and proliferation of cancer cells.
An antibody-drug conjugate composed of an antibody directed against 5T4 and conjugated, via the stable linker maleimidocaproyl (mc), to the microtubule inhibitor monomethyl auristatin phenylalanine (MMAF), with potential antineoplastic activity. Upon administration, the antibody moiety of PF-06263507 selectively binds to cells expressing the 5T4 oncofetal antigen. After internalization and enzymatic cleavage of the immunoconjugate within the tumor cell cytosol, free MMAF binds to tubulin and inhibits its polymerization, which may result in G2/M phase arrest and tumor cell apoptosis. 5T4, a transmembrane glycoprotein, is overexpressed by a variety of cancer cell types; its expression is correlated with increased invasiveness.
A liposomal nanoparticle-based therapeutic vaccine composed of the cationic lipid R-DOTAP (R-enantiomer of 1,2-dioleoyl-3-trimethylammonium-propane chloride) encapsulating six human papillomavirus 16 (HPV-16) E6 and E7 peptides, with potential immunostimulating activity. Upon subcutaneous administration of the liposomal HPV-16 E6 and E7 multipeptide vaccine, the nanoparticles are taken up by antigen presenting cells (APCs), specifically dendritic cells (DCs), which may stimulate the immune system to induce a cytotoxic T-lymphocyte response (CTL) against HPV-16 E6 and E7-expressing tumor cells. HPV-16 E6 and E7 are oncoproteins that play a key role in the tumorigenesis of a variety of cancers.
A long-acting formulation of recombinant interferon alpha subtype 2b (IFN-a2b) protein, in which IFN-a2b is coupled, via proline, to polyethylene glycol (PEG), with antiviral, immunomodulating and antineoplastic activities. Upon subcutaneous administration, IFN-a2b binds to specific interferon cell-surface receptors. This activates interferon-mediated signal transduction pathways and induces the transcription and translation of genes with interferon-specific response elements (ISREs); the protein products mediate antiviral, antiproliferative, anticancer, and immune-modulating effects. The PEG moiety inhibits proteolytic breakdown and clearance of IFN-a2b, which prolongs its half-life, extends the duration of its therapeutic effects and allows less frequent dosing. The proline linker facilitates the synthesis of a predominant (90%) positional isomer which allows for further increases in stability and a longer half-life than previous PEG conjugates.
An orally available inhibitor of maternal embryonic leucine zipper kinase (MELK) with potential antineoplastic activity. Upon administration, OTS167 binds to MELK, which prevents both MELK phosphorylation and activation; thus inhibiting the phosphorylation of downstream MELK substrates. This may lead to an inhibition of both cell proliferation and survival in MELK-expressing tumor cells. MELK, a serine/threonine kinase, is involved in cancer cell survival, invasiveness and cancer-stem cell formation and maintenance; it is highly upregulated in various types of cancer cells and absent in normal, healthy cells.
A peptide cancer vaccine comprised of a peptide derived from Wilms tumor gene 1 (WT1) protein, with potential immunomodulating and antineoplastic activities. Upon subcutaneous administration, WT1 peptide vaccine OCV-501 may stimulate a CD4-positive helper T-lymphocyte-mediated immune response against WT1 expressing cells. WT1 protein, a zinc finger DNA-binding protein, is overexpressed in leukemic cells and in some solid tumors.
Allogeneic natural killer (NK) cells transduced with an mRNA expressing a chimeric antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment) and the zeta chain of the TCR/CD3 complex (CD3-zeta), coupled to the signaling domain of 4-1BB (CD137), with potential immunomodulating and antineoplastic activities. NK cells from haploidentical donors are expanded in culture and electroporated with the CAR mRNA. Upon transfusion of the transduced cultured cells, CD19CAR-CD3zeta-4-1BB-expressing allogeneic NK cells bind to and induce selective cytotoxicity in CD19-expressing tumor cells. The 4-1BB co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19. Its inclusion may also increase antitumor activity, when compared to the inclusion of the CD3-zeta chain alone. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies.
Polymeric micellar nanoparticles containing diaminocyclohexane platinum (DACH-platin or DACH-Pt) with potential antineoplastic activity. DACH-platin micelle NC-4016 is prepared through the formation of a polymer-metal complex between DACH-platin and the polyethylene glycol-poly (glutamic acid) block copolymer, PEG-P(Glu). DACH-platin, an active metabolite of the platinum-based antineoplastic agent oxaliplatin, is highly hydrophobic and toxic when administered systemically. The use of polymeric micelles incorporating DACH-platin may both increase cell permeability and enhance the retention of the agent. This allows an extended half-life in the blood circulation and a selective and high accumulation of DACH-platin at tumor sites. This results in increased anticancer efficacy while reducing side effects due to DACH-platin toxicity. Upon intravenous administration and internalization by tumor cells, DACH-platin binds to and causes both inter- and intra-strand cross-links in DNA, forming platinum adducts and triggering tumor cell apoptosis.
An orally available inhibitor of the serine/threonine protein kinases ribosomal protein S6 Kinase (p70S6K) and Akt (protein kinase B), with potential antineoplastic activity. Upon administration, p70S6K/Akt inhibitor MSC2363318A binds to and inhibits the activity of p70S6K and Akt. This prevents the activation of the PI3K/Akt/p70S6K signaling pathway and inhibits tumor cell proliferation in cancer cells that have an overactivated PI3K/Akt/p70S6K signaling pathway. Constitutive activation and dysregulated signaling of the PI3K/Akt/p70S6K pathway are frequently associated with tumorigenesis of many tumor types; targeting multiple kinases in this pathway is more efficacious than targeting a single kinase.
An orally bioavailable inhibitor of the proto-oncogene c-Met (also known as hepatocyte growth factor receptor (HGFR)) with potential antineoplastic activity. c-Met inhibitor MSC2156119J selectively binds to c-Met, which inhibits c-Met phosphorylation and disrupts c-Met-mediated signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.
A recombinant, human monoclonal antibody targeting an extracellular epitope of human prostate specific membrane antigen (PSMA) that is conjugated with a fluorescent dye A488, with potential imaging activity. Upon intravenous administration, the MDX1201 moiety of anti-PSMA monoclonal antibody MDX1201-A488 targets PSMA expressed on cancer cells. Subsequently, the A488 moiety can then be visualized by fluorescence-based imaging and the amount of PSMA-expressing tumor cells can be assessed. A488 is a photostable fluorescent dye with a high quantum yield. PSMA, a tumor-associated antigen and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells.
An inhibitor of CXC chemokine receptor 4 (CXCR4), with potential antineoplastic activity. Upon subcutaneous administration, CXCR4 inhibitor LY2510924 binds to the chemokine receptor CXCR4, thereby preventing CXCR4 binding to its ligand, stromal derived factor-1 (SDF-1), and subsequent receptor activation. This may result in decreased tumor cell proliferation and migration. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types.
An orally available pan-PIM protein kinase inhibitor with potential antineoplastic activity. PIM kinase inhibitor LGH447 binds to and inhibits the activities of PIM-1, -2 and -3 serine/threonine kinases, which may result in the interruption of the G1/S phase cell cycle transition, the expression of the pro-apoptotic Bcl2 protein and tumor cell apoptosis in cells that overexpress PIMs. PIM kinases, downstream effectors of many cytokine and growth factor signaling pathways, play key roles in cell cycle progression and apoptosis inhibition and may be overexpressed in various malignancies.
A water soluble inhibitor of the protein phosphatase 2A (PP2A), with potential chemo- and radiotherapy enhancing activity. Upon injection, PP2A inhibitor LB-100 inhibits the removal of phosphate groups from proteins essential for cell cycle progression. When used with radio- or chemotherapy treatment, this agent prevents the activation of PP2A-mediated repair mechanisms and allows for malignant cells to progress through the cell cycle without having their damaged DNA repaired. This enhances the cytotoxic effect of the chemotherapeutic or radiotherapeutic agent and results in tumor cell apoptosis. PP2A, a serine/threonine phosphatase that plays a key role in the control of cell growth and DNA damage repair.
A therapeutic peptide vaccine consisting of thirteen synthetic long peptides (SLPs), which are 25-35 amino acids in size, derived from the human papillomavirus (HPV) type 16 oncoproteins E6 and E7, with potential immunostimulating and antitumor activities. Upon administration, synthetic long E6/E7 peptides vaccine HPV-01 is taken up and degraded into small pieces by dendritic cells. The processed viral epitopes are presented by dendritic cells, which may stimulate the host immune system to mount both cytotoxic T-cell lymphocyte (CTL) and helper T cell responses against HPV E6/E7-expressing tumor cells. This results in the destruction of tumor cells and leads to decreased tumor growth. The E6 and E7 oncoproteins are implicated in the tumorigenesis in a variety of cancers. The SLPs allow for optimal presentation by antigen-presenting cells.
An inhibitor of the delta isoform of phosphoinositide-3 kinase (PI3K) with potential antineoplastic activity. PI3K-delta inhibitor INCB050465 inhibits the delta isoform of PI3K and prevents the activation of the PI3K/AKT signaling pathway. This both decreases proliferation and induces cell death in PI3K-delta-overexpressing tumor cells. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in hematopoietic disease and cell lineages. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival.
An orally bioavailable inhibitor of Janus-associated kinases (JAK), with potential antineoplastic activity. Upon oral administration, INCB047986 specifically binds to and inhibits the phosphorylation of JAK, which affects JAK-dependent signaling and may lead to an inhibition of cellular proliferation in JAK-overexpressing tumor cells. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies.
A targeted antibody payload (TAP)-based immunoconjugate consisting of a human monoclonal antibody directed against the epidermal growth factor receptor (EGFR) conjugated, via a nonreducible thioether linker (succinimidyl trans-4-(maleimidylmethyl)cyclohexane-1-carboxylate or SMCC), to the cytotoxic agent maytansinoid mertansine (DM1), with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of immunoconjugate IMGN289 binds to and inhibits EGFR on tumor cell surfaces. Inhibition of EGFR prevents EGFR-mediated signaling and may inhibit tumor cell proliferation. After internalization, the mertansine moiety binds to tubulin and interferes with microtubule assembly/disassembly dynamics. This inhibits both cell division and the proliferation of cancer cells that express EGFR. EGFR, overexpressed by a variety of cancers, plays a key role in tumor cell proliferation and survival. Linkage of the antibody and drug, through a nonreducible linker, appears to contribute to the improved efficacy and reduced toxicity of this antibody-drug conjugate (ADC) compared to similar ADCs constructed with reducible linkers.
A monoclonal antibody directed against the cell surface protein claudin 6 (CLDN6), with potential immunostimulating and antineoplastic activities. Upon administration, the anti-CLDN6 monoclonal antibody IMAB027 binds to CLDN-6 and may stimulate the immune system to exert both an antibody-dependent cellular cytotoxicity (ADCC) and a complement-dependent cytotoxicity (CDC) mediated immune response against CLDN-6-expressing tumor cells. This may inhibit tumor cell growth. CLDN-6, a tight-junction protein and embryonic antigen, is expressed on a variety of tumor cells but is not expressed on normal, healthy adult cells.
Human autologous peripheral blood lymphocytes (PBLs) transduced with two retroviral vectors, one encoding a T-cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1 and a second that encodes an inducible single chain form of interleukin-12 (IL-12) driven by a nuclear factor of activated T-cells (NFAT)-responsive promoter, with potential immunomodulating and antineoplastic activities. Following isolation of lymphocytes, retroviral vector transduction, and expansion of the cells ex vivo, the inducible IL-12/anti-NY-ESO-1 TCR-expressing autologous PBLs are re-administered into the patient by intravenous injection. As the transduced PBLs traverse the patient's circulation, they can bind to NY-ESO-1-overexpressing tumor cells. This binding activates the TCR signaling pathway in the transduced PBLs, which promotes NFAT-dependent gene transcription and induces expression of the cotransduced IL-12. IL-12 expression activates the immune system by promoting the secretion of interferon-gamma, activating natural killer cells (NKs), and inducing cytotoxic T-cell responses, which may result in both decreased cell proliferation and increased cell death for the NY-ESO-1-overexpressing tumor cells. NY-ESO-1, a tumor associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types. NFAT, a family of transcription factors involved in immune responses, is activated by calcium signaling, which can occur downstream of TCR activation. Use of a retroviral vector to express an inducible IL-12 may remove the requirement for concomitant administration of interleukin-2 (IL-2) as is the case for conventional cell transfer immunotherapies.
A cancer vaccine composed of a recombinant form of the tumor antigen NY-ESO-1 and glucopyranosyl lipid adjuvant (GLA)-stable emulsion (GLA-SE), with potential antineoplastic and immunomodulating activities. Upon intramuscular injection, the adjuvant portion of the NY-ESO-1/GLA-SE vaccine ID-G30 binds to toll-like receptor subtype 4 (TLR-4) expressed on dendritic cells (DCs), monocytes, macrophages and B cells. The activated DCs present the NY-ESO-1 antigen to Th1 CD4 T-lymphocytes. This leads to the induction of cytotoxic T lymphocytes (CTLs) and the killing of NY-ESO-1-expressing tumor cells. This vaccine also induces specific antibody responses and increases the production of inflammatory cytokines.
An umbilical cord blood product that has been expanded ex vivo and can be used during single umbilical cord blood transplantation.
An allogeneic urothelial bladder cancer cell vaccine expressing a recombinant secretory form of the immunoadjuvant heat shock protein gp96 fused with an immunoglobulin Fc domain (gp96-Ig) protein, with potential antineoplastic activity. Upon administration of the gp96-Ig-secreting allogeneic bladder cancer cell vaccine HS-410, the live, irradiated tumor cells continuously secrete gp96-Ig along with its chaperoned tumor associated antigens (TAAs). This enhances antigen cross presentation to cytotoxic T-lymphocytes (CTLs) and, upon expansion, leads to the induction of a potent CTL response against the TAAs on the endogenous bladder cancer cells. This vaccine also induces a memory T cell response that could fight recurring cancer cells. gp96-Ig is constructed by replacing the KDEL endoplasmic reticulum (ER) retention sequence of gp96 with the Fc portion of the IgG1 protein. This allows for gp96, normally an ER-resident chaperone peptide, to be released from cells.
An inhibitor of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter P-glycoprotein (P-gp), with adjuvant activity. Upon oral administration, P-gp inhibitor HM30181AK selectively binds to and inhibits the multidrug resistance (MDR) efflux pump P-gp, which prevents the efflux of various chemotherapeutic agents from intestinal epithelial cells to the gastrointestinal tract. This leads to an increase in both oral bioavailability and therapeutic efficacy. P-gp prevents the intestinal uptake and intracellular accumulation of various cytotoxic agents. HM30181AK is not systemically absorbed.
A replication selective, recombinant, E1B and partial E3 gene deleted form of human adenovirus type 5, with potential antineoplastic activity. Upon intratumoral injection of recombinant human adenovirus type 5, the adenovirus selectively replicates in cancer cells while preventing viral replication in normal, healthy cells. This induces a selective adenovirus-mediated cytotoxicity in cancer cells, which leads to cancer cell lysis. In addition, viral spread to adjacent cells, following lysis of infected cells, may activate the immune system to kill the infected tumor cells. The E1B protein causes p53 inactivation, which promotes viral replication; deletion of E1B allows for p53 activation in normal cells, which prevents viral replication in normal, healthy cells. The mutation and subsequent inactivation of p53 in cancer cells enables the E1B-deleted adenovirus to selectively replicate in cancer cells. Partial deletion of E3, encoding the adenovirus death protein, enhances the safety profile of the administered adenovirus.
An orally available, irreversible, inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, GSK2879552 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the dimethylated form of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival.
A small molecule selective and S-adenosyl methionine (SAM) competitive inhibitor of histone-lysine N-methyltransferase EZH2, with potential antineoplastic activity. Upon administration, histone-lysine N-methyltransferase EZH2 inhibitor GSK2816126 inhibits the activity of EZH2 and specifically prevents the methylation of histone H3 lysine 27 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased tumor cell proliferation in cancer cells that overexpress this enzyme. EZH2, which belongs to the class of histone methyltransferases (HMTs), is overexpressed or mutated in a variety of cancers and plays a key role in tumor cell proliferation.
An orally bioavailable, substituted benzimidazole inhibitor of the class I phosphoinositide 3-kinase (PI3K) beta isoform with potential antineoplastic activity. PI3K beta inhibitor GSK2636771 selectively inhibits PI3K beta kinase activity in the PI3K/Akt/mTOR pathway, which may result in tumor cell apoptosis and growth inhibition in PI3K beta-expressing and/or PTEN-driven tumor cells. Dysregulation of the PI3K/Akt/mTOR pathway is frequently found in solid tumors and results in the promotion of tumor cell growth, survival, and resistance to both chemotherapy and radiotherapy. PI3K beta is the p110-beta catalytic subunit of the class I PI3K. PTEN, a tumor suppressor protein and negative regulator of PI3K activity, is often mutated in a variety of cancer cells.
A humanized monoclonal antibody against matrix metalloproteinase 9 (MMP-9), with potential antineoplastic activity. Upon administration, anti-MMP-9 monoclonal antibody GS-5745 binds to MMP-9 and inhibits its enzymatic activity. This results in an inhibition of extracellular matrix protein degradation and, potentially, the inhibition of angiogenesis, tumor growth, invasion, and metastasis. MMP-9, a protein belonging to the MMP family, plays a key role in the degradation of collagens and proteoglycans; increased activity of MMP-9 has been associated with increased invasion and metastasis of cancer.
An orally available antagonist of the nociceptin receptor opioid receptor like -1 (ORL-1), with potential analgesic activity. Upon oral administration, cebranopadol binds to ORL-1 and prevents its interaction with nociceptin. This leads to a decrease of nociceptin/ORL-1-mediated signaling and interferes with the sensation of pain, which results in an analgesic effect. Nociceptin is a neuropeptide involved in the regulation of pain.
A formylated, six amino acid, Wnt5a-derived peptide and wnt-5a mimetic with potential anti-metastatic activity. Upon intravenous administration, Wnt-5a mimic hexapeptide foxy-5 binds to and activates the wnt-5a receptors, Frizzled-2 and -5, which activates wnt-5a-mediated signaling. Increased wnt-5a signaling may inhibit endothelial tumor cell migration and invasion. This may decrease metastasis of susceptible tumor cells. However, foxy-5 does not affect tumor cell proliferation or apoptosis. Foxy-5 lacks a heparan sulfate-binding domain and contains a formyl group on its NH2-terminal methionine residue which decreases in vivo degradation. Decreased expression of wnt-5a protein is associated with increased motility of certain tumor cell types.
An orally bioavailable inhibitor of the fibroblast growth factor receptor subtypes 1 (FGFR-1), 2 (FGFR-2) and 3 (FGFR-3), with potential antineoplastic activity. FGFR inhibitor debio 1347 binds to and inhibits FGFR-1, -2, and -3, which result in the inhibition of FGFR-mediated signal transduction pathways. This leads to the inhibition of both tumor cell proliferation and angiogenesis, and causes cell death in FGFR-overexpressing tumor cells. FGFR, a family of receptor tyrosine kinases upregulated in many tumor cell types, is essential for tumor cellular proliferation, differentiation and survival.
An injectable targeted small molecule drug conjugate (SMDC) consisting of folate (vitamin B9) covalently linked to the potent mitotic poison and cytotoxic agent, tubulysin B hydrazide (Tub-B-H) with potential antineoplastic activity. Upon administration, the folate moiety of folate receptor-targeted tubulysin conjugate EC1456 preferentially binds to tumor cells expressing folate receptors (FR). After binding to FR, the agent is internalized by tumor cells and the Tub-B-H moiety inhibits the polymerization of tubulin into microtubules. This may lead to both cell cycle arrest and tumor cell apoptosis. FR, the membrane-bound, high-affinity receptor for folate, is overexpressed on a wide range of primary and metastatic human cancers.
A traditional Chinese medicine (TCM)-based formulation containing the Yangzheng Xiaoji (YZXJ) extract, consisting of various components, with potential antineoplastic and anti-angiogenic activities. Some of the main components in Yangzheng Xiaoji are Radix Astragali, Fructus Ligustri Lucidi, Radix Ginseng, Ganoderma, Rhizoma Curcumac, Fried Rhizoma Atractylodis, Macrocephalae and Herba Hedyotidis. Although the exact mechanism(s) through which Yangzheng Xiaoji exerts its effects have yet to be fully elucidated, this agent, upon administration, inhibits the activation of various signaling protein kinases, such as focal adhesion kinase (FAK) and paxillin. This prevents signal transduction pathways that are upregulated in cancer, prevents the adhesion and migration of tumor cells and inhibits tumor cell growth.
A low-fucosylated, humanized, IgG1 isotype, monoclonal antibody directed against the B-cell-specific membrane protein CD19 with potential immunostimulating and antineoplastic activities. Anti-CD19 monoclonal antibody DI-B4 binds to CD19, which may result in a strong antibody-dependent cellular cytotoxicity (ADCC) directed at CD19-expressing B-cells but with minimal complement dependent cytotoxicity. DI-B4 contains low levels of fucose, which contributes to its enhanced ADCC activity. CD19 is a B-cell specific membrane antigen that is widely expressed during B-cell development and in all B-cell lineage malignancies.
An orally available, mucoadhesive lipid preparation consisting of paclitaxel, a compound extracted from the Pacific yew tree Taxus brevifolia, in a formulation that is comprised of a mixture of monoolein, tricarprylin, and Tween 80, with potential antineoplastic activity. Upon oral administration, DHP107 forms droplets and micelles in the intestine; these adhere to mucoepithelial cells in the gastrointestinal tract and are absorbed through lipid-based uptake mechanisms. Upon absorption, paclitaxel binds to and stabilizes tubulin molecules, which results in the inhibition of both microtubule depolymerization and cell division. This agent also induces apoptosis by both binding to and blocking the function of the apoptosis inhibitor protein B-cell Leukemia 2 (Bcl-2).The mucoadhesive paclitaxel formulation does not contain P-glycoprotein inhibitors, the solvent cremophor or any other toxic solvent.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against a specific myeloma antigen and conjugated to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule inhibitor, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of DFRF4539A selectively binds to a specific protein expressed on the surface of myeloma cells. Upon internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and tumor cell apoptosis.
A non-small cell lung cancer (NSCLC) vaccine containing six modified mRNAs, which encode six different NSCLC associated antigens, with potential antitumor and immunomodulatory activities. Upon intradermal administration, mRNA-derived lung cancer vaccine CV9202 may stimulate the immune system to mount both humoral and cellular responses against NSCLC cells. The six tumor-associated antigens (TAAs) encoded by these mRNAs are frequently expressed by NSCLC cells and are minimally expressed or absent in normal, healthy cells.
A prostate cancer vaccine containing six messenger RNAs (mRNAs) encoding for antigens upregulated in prostate cancer, including mRNAs for prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), prostatic acid phosphatase (PAP), and mucin 1 (MUC1), with potential antineoplastic and immunomodulating activities. Upon intradermal administration of mRNA-derived prostate cancer vaccine CV9104, this agent enters cells, the mRNAs are translated into the respective prostate specific antigens and may cause the immune system to mount a cytotoxic T lymphocyte response (CTL) against PSA-, PSMA-, PAP- and MUC1-expressing prostate tumor cells. The mRNAs used in this vaccine are modified to have enhanced translational potency and adjuvant activities. PSA, PSMA, PAP and MUC1 are frequently upregulated in prostate cancer cells; their expression in prostate cancer has been correlated with disease progression.
An autologous tumor cell vaccine containing CD34+ hematopoietic progenitor cell (HPC)-derived Langerhans-type dendritic cells (LCs) electroporated with mRNA encoding the full-length cancer-testis antigens, CT7 and melanoma-associated antigen 3 (MAGE-A3), and the self-differentiation tumor antigen, Wilms tumor 1 (WT1) with potential immunomodulating and antineoplastic activity. The autologous CT7/MAGE-A3/WT1 mRNA-electroporated Langerhans-type dendritic cells are prepared by drawing a blood sample containing the CD34+ HPCs from a cancer patient. The CD34+ HPCs are treated with a combination of cytokines which specifically support LC development, and the LC population is enriched and expanded ex vivo. The cultured LCs are allowed to mature for one day and then electroporated separately with CT7, MAGE-A3 or WT1 mRNA before final maturation. Upon intradermal administration into the patient, the mature LCs may activate cell-mediated immunity and induce both cytotoxic CD8+ T cells and CD4+ helper T cells against cancer cells expressing CT7, MAGE-A3 and WT1 tumor antigens. This may result in the immune-mediated inhibition of tumor cell proliferation, leading to tumor cell death. CT7 and MAGE-A3 are tumor-specific proteins overexpressed in a number of cancers but not in healthy tissues other than testis and placenta. WT1 is a transcription factor important in development and cancer pathogenesis, which is overexpressed in a variety of cancers, including multiple myeloma, leukemia, ovarian cancer, malignant mesothelioma, neural tumors and renal carcinoma.
A small molecule inhibitor of the Bromodomain and Extra-Terminal (BET) family of proteins, with potential antineoplastic activity. Upon administration, the BET inhibitor CPI-0610 binds to the acetylated lysine recognition motifs on the bromodomain of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histone peptides. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth. Characterized by a tandem repeat of two bromodomains at the N-terminus, the BET proteins (BRD2, BRD3, BRD4 and BRDT) are transcriptional regulators that play an important role during development and cellular growth.
The besylate salt form of crenolanib, an orally bioavailable benzimidazole targeting the platelet-derived growth factor receptor (PDGFR) subtypes alpha and beta and FMS-related tyrosine kinase 3 (Flt3), with potential antineoplastic activity. Upon oral administration, crenolanib binds to and inhibits both wild-type and mutated forms of PDGFR and Flt3, which may result in the inhibition of PDGFR- and Flt3-related signal transduction pathways. This results in inhibition of tumor angiogenesis and tumor cell proliferation in PDGFR and/or Flt3 overexpressing tumor cells. PDGFR and Flt3, class III receptor tyrosine kinases, are upregulated or mutated in many tumor cell types.
A complex, replication-selective, E1B and partial E3 gene deleted, adenovirus type 11p (Ad11p)/Ad3 chimeric oncolytic virus with potential antineoplastic activity. Upon intralesional injection of enadenotucirev, the adenovirus selectively and rapidly replicates in cancer cells; however, it is unable to replicate in normal, healthy cells. This induces a selective adenovirus-mediated cytotoxicity in cancer cells, which leads to cancer cell lysis. Following the lysis of infected cells, the replicated virus is released and can infect adjacent cells, which both induces further tumor cell oncolysis and may activate the immune system to kill the infected tumor cells. The E1B protein causes p53 inactivation in host cells, which promotes viral replication. Deletion of E1B prevents replication in normal, healthy cells that express wild-type p53. The mutation and subsequent inactivation of p53 in cancer cells enables the E1B-deleted adenovirus to selectively replicate in cancer cells. Partial deletion of the E3 gene, which encodes the adenovirus death protein, enhances the safety profile of the administered adenovirus.
An immunoconjugate comprised of the recombinant chimeric monoclonal antibody cetuximab conjugated to the N-hydroxysuccinamide (NHS) ester form of the near-infrared (NIR) fluorescent dye IRDye 800CW (cetuximab-IRDye 800) with potential imaging use. The antibody moiety of cetuximab-IRDye 800 binds to the extracellular domain of the epidermal growth factor receptor (EGFR). Upon binding, IRDye 800 may be detected using NIR imaging, which facilitates the visualization and quantification of EGFR-expressing tumor cells. EGFR is a receptor tyrosine kinase that may be overexpressed on the cell surfaces of various tumor types.
An orally available dual kinase inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) and focal adhesion kinase (FAK), with potential antineoplastic activity. Upon administration, ALK-FAK inhibitor CEP-37440 selectively binds to and inhibits ALK kinase and FAK kinase. The inhibition leads to disruption of ALK- and FAK-mediated signal transduction pathways and eventually inhibits tumor cell growth in ALK- and FAK-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; its dysregulation and gene rearrangements are associated with a variety of tumors. The cytoplasmic tyrosine kinase FAK, a signal transducer for integrins, is upregulated and constitutively activated in various tumor types; it plays a key role in tumor cell migration, proliferation, survival, and tumor angiogenesis.
An orally available curaxin-based agent targeting the Facilitates Chromatin Transcription (FACT) complex, with potential antineoplastic activity. Upon administration, CBL0137 binds to FACT and sequesters the FACT complex on chromatin, which inhibits its activity. This prevents transcription of certain genes involved in cancer-associated signaling pathways; it specifically inhibits the transcription of both NF-kappa B and heat shock transcription factor 1 (HSF1) and simultaneously activates p53. This causes an increase in tumor cell apoptosis and a decrease in tumor cell proliferation, in FACT-positive cancers. In addition, this agent is able to sensitize FACT-positive tumor cells to the cytotoxic effects of other chemotherapeutic agents. FACT, a transcription and replication factor composed of the Structure Specific Recognition Protein (SSRP1) and suppressor of Ty 16 (Spt16) proteins, is expressed in a variety of tumor cells while almost absent in normal cells; its expression is associated with increased tumor aggressiveness and poor prognosis.
An orally bioavailable inhibitor of glutaminase, with potential antineoplastic activity. Upon oral administration, CB-839 selectively and irreversibly inhibits glutaminase, a mitochondrial enzyme that is essential for the conversion of the amino acid glutamine into glutamate. By blocking glutamine utilization, proliferation in rapidly growing cells is impaired. Glutamine-dependent tumors rely on the conversion of exogenous glutamine into glutamate and glutamate metabolites to both provide energy and generate building blocks for the production of macromolecules, which are needed for cellular growth and survival.
A genetically-modified, dendritic cell-based (DCs) vaccine in which the autologous cells are transduced with an adenoviral vector expressing the tumor antigen prostate-specific membrane antigen (PSMA) and a fusion protein composed of synthetic ligand inducible adjuvant iMC composed of a drug-inducible costimulatory CD40 receptor (iCD40) and the adaptor protein MyD88, with potential immunomodulating and antineoplastic activities. The iCD40 contains a membrane-localized cytoplasmic CD40 domain fused to the FK506 modified drug-binding protein 12 (FKBP12). Upon intradermal administration of BPX-201, these DCs accumulate in local draining lymph nodes. Twenty-four hours after vaccination, the dimerizing agent AP1903 is administered. AP1903 binds to the drug binding domain, leading to iMC oligomerization and activation of iCD40 and MyD88-mediated signaling in iMC-expressing DCs. This signaling pathway activates the DCs and stimulates a cytotoxic T-lymphocyte (CTL) response against host tumor cells that express PSMA. PSMA, a glycoprotein secreted by prostatic epithelial and ductal cells, is overexpressed in prostate cancer cells and is used as a tumor marker for both diagnosis and treatment evaluation. MyD88 is involved in interleukin 1 receptor (IL1R) and toll-like receptor (TLR) signaling.
A combination agent composed of the benzo-poly-carbonic-acid polymer BP-Cx1 chelated to platinum with potential antineoplastic activity. Upon intramuscular injection, the polymer moiety of BP-Cx1-Platinum Complex BP-C1 (BP-C1) alters the permeability of the cell membranes, which allows for increased penetration of platinum into tumor cells. In turn, platinum binds to nucleophilic groups such as GC-rich sites in DNA and induces intrastrand and interstrand DNA cross-links, as well as DNA-protein cross-links. These cross-links result in apoptosis and cell growth inhibition. In addition, the BP-Cx1 ligand is able to stimulate the innate immune system and upregulates a variety of cytokines including interferon, tumor necrosis factor-alpha (TNF-alpha), granulocyte macrophage-colony stimulating factor (GM-CSF), and various interleukins (ILs) such as IL-6 and IL-25. In comparison to cisplatin and other platinum-based compounds, treatment with BP-C1 allows for less platinum administration, which reduces platinum-associated systemic toxicity and side effects, and enhances the safety profile while maintaining or improving its efficacy.
A monoclonal antibody directed against the inhibitor receptor lymphocyte activation gene-3 (LAG-3), with potential immunomodulating and antineoplastic activities. Upon administration, the anti-LAG-3 monoclonal antibody BMS-986016 binds to LAG-3 on tumor infiltrating lymphocytes (TILs). This may activate antigen-specific T-lymphocytes and enhance cytotoxic T cell-mediated tumor cell lysis, which leads to a reduction in tumor growth. LAG-3 is a member of the immunoglobulin superfamily (IgSF) and binds to major histocompatibility complex (MHC) class II. LAG-3 expression on TILs is associated with tumor-mediated immune suppression.
An orally bioavailable tyrosine kinase inhibitor of the BCR-ABL fusion oncoprotein, with potential antineoplastic activity. Upon oral administration, BCR-ABL tyrosine kinase inhibitor BL001 may inhibit the BCL-ABL protein, which may lead to decreased proliferation and enhanced apoptosis in tumor cells. BCR-ABL oncoprotein is generated by a reciprocal translocation between chromosome 9 and 22 specifically t(9;22)(q34;q11). The resulting fusion gene produces proteins with constitutively active tyrosine kinase activity, which stimulate both abnormal cell division and increased cellular proliferation. This fusion is associated with both chronic myeloid leukemia and acute lymphoblastic leukemia.
An orally available dual inhibitor of mitogen-activated protein kinase kinase (MEK) and Aurora kinases, with potential antineoplastic activity. Upon oral administration, MEK/Aurora kinase inhibitor BI 847325 selectively binds to and inhibits the activity of MEK, which both prevents the activation of MEK-dependent effector proteins and inhibits growth factor-mediated cell signaling. BI 847325 also binds to and inhibits the activity of the Aurora kinases A, B and C which may disrupt the assembly of the mitotic spindle apparatus, prevent chromosome segregation, and inhibit both cellular division and proliferation in Aurora kinase-overexpressing tumor cells. Altogether, this leads to the inhibition of cell proliferation and tumor growth as well as the induction of tumor regression. MEK, a dual-specificity threonine/tyrosine kinase that plays a key role in the activation of the RAS/RAF/MEK/ERK signaling pathway, is frequently upregulated in a variety of tumor cell types. Aurora kinases are serine-threonine kinases that play essential roles in mitotic checkpoint control and are overexpressed by a wide variety of cancer cell types.
An antibody against the fibroblast growth factor receptor type 2 (FGFR2), with potential antineoplastic activity. Upon administration, the anti-FGFR2 antibody BAY1179470 binds to and inhibits FGFR2, which may result in the inhibition of both FGFR2 phosphorylation and FGFR2-mediated signal transduction pathways. This results in the inhibition of cell proliferation and the induction of cell death of FGFR2-expressing tumor cells. FGFR2, upregulated in many tumor cell types, is a receptor tyrosine kinase, which is essential to tumor cellular proliferation, differentiation and survival.
A pan inhibitor of human fibroblast growth factor receptors (FGFRs) with potential antiangiogenic and antineoplastic activities. Pan-FGFR kinase inhibitor BAY1163877 inhibits the activities of FGFRs, which may result in the inhibition of both tumor angiogenesis and tumor cell proliferation, and the induction of tumor cell death. FGFRs are a family of receptor tyrosine kinases, which may be upregulated in various tumor cell types and may be involved in tumor cell differentiation and proliferation, tumor angiogenesis, and tumor cell survival.
An orally bioavailable inhibitor of the serine/threonine protein kinase AKT (protein kinase B) isoforms 1 and 2 (AKT1/2) with potential antineoplastic activity. AKT1/2 inhibitor BAY1125976 selectively binds to and inhibits the phosphorylation and activity of AKT1/2 in a non-ATP competitive manner, which may result in the inhibition of the phosphatidylinositol 3 (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. This may lead to both the reduction of cell proliferation and the induction of cell apoptosis in AKT-overexpressing tumor cells. The AKT signaling pathway is often deregulated in cancer and is associated with tumor cell proliferation, survival and migration.
An inhibitor of the beta isoform of phosphoinositide-3 kinase (PI3K), with potential antineoplastic activity. Upon administration, PI3Kbeta inhibitor AZD8186 selectively inhibits the activity of PI3Kbeta in the PI3K/Akt/mTOR signaling pathway, which may result in a decrease of tumor cell proliferation and induces cell death in PI3K-expressing cancer cells. By specifically targeting class I PI3K beta, this agent may be more efficacious and less toxic than pan PI3K inhibitors. PI3K-mediated signaling is often dysregulated in cancer cells and contributes to increased tumor cell growth, survival, and tumor resistance to a variety of antineoplastic agents.
An orally available morpholino-pyrimidine-based inhibitor of ataxia telangiectasia and rad3 related (ATR) kinase, with potential antineoplastic activity. Upon oral administration, ATR kinase inhibitor AZD6738 selectively inhibits ATR activity by blocking the downstream phosphorylation of the serine/threonine protein kinase CHK1. This prevents ATR-mediated signaling, and results in the inhibition of DNA damage checkpoint activation, disruption of DNA damage repair, and the induction of tumor cell apoptosis. In addition, AZD6738 sensitizes tumor cells to chemo- and radiotherapy. ATR, a serine/threonine protein kinase upregulated in a variety of cancer cell types, plays a key role in DNA repair, cell cycle progression and survival; it is activated by DNA damage caused during DNA replication-associated stress.
A poloxamer-formulated, bivalent DNA vaccine containing two plasmids encoding both the human cytomegaloviral (CMV) tegument phosphoprotein 65 (pp65), a major internal matrix protein, and glycoprotein B (gB), an important CMV component responsible for attachment and entry into cells, with potential immunostimulatory properties. Upon intramuscular injection of CMVpp65/gB plasmid vaccine ASP0113, the expressed proteins may activate the immune system to mount both cellular and humoral immune responses against CMV-positive cells. This results in cell lysis of CMV-infected cells and prevents both viral replication and the development of CMV disease. This vaccine also provides active immunization and protective immunity against CMV infection in CMV-negative patients exposed to infected donor cells or tissues in transplant recipients. CMV infection can cause serious complications in patients receiving either allogeneic hematopoietic cell transplants (HCT) or solid organ transplants. The poloxamer-based delivery system enhances DNA delivery.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against SLIT and NTRK-like protein 6 (SLITRK6), covalently linked to the cytotoxic agent monomethyl auristatin E (MMAE), an auristatin derivative and a potent inhibitor of microtubule polymerization, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of AGS15E binds to SLITRK6 expressed on tumor cells, which facilitates both AGS15E internalization and the intracellular delivery of MMAE. Upon cleavage, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and tumor cell apoptosis. SLITRK6, a member of the Slitrk family of leucine-rich repeat (LRR) neuronal transmembrane proteins, is minimally expressed in normal tissue but overexpressed in a variety of cancers, including bladder cancer, some forms of lung cancer, breast cancer and glioblastoma.
A defucosylated, humanized IgG1 monoclonal antibody directed against the extracellular domain of the human CD70 molecule with potential antineoplastic activity. Upon administration, anti-CD70 monoclonal antibody ARGX-110 selectively binds to, and neutralizes the activity of CD70, which may also induce an antibody-dependent cellular cytotoxicity (ADCC) response against CD70-expressing tumor cells. CD70, the ligand for the costimulatory receptor CD27 and a member of the tumor necrosis factor (TNF) family, is found on a number of solid and hematological tumors. Its overexpression may play an important role in evasion of immune surveillance.
An immunoconjugate consisting of a human IgG1 monoclonal antibody directed against CD27L conjugated, via a non-cleavable linker, to the cytotoxic agent maytansinoid DM1, with potential antineoplastic activity. The monoclonal antibody moiety of this immunoconjugate binds to CD27L on tumor cell surfaces. After internalization, the DM1 moiety binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics and inhibiting both cell division and proliferation of cancer cells that express CD27L. CD27L, a type II transmembrane protein and member of the tumor necrosis factor family, is a co-stimulatory molecule constitutively expressed on a subset of activated T-cells, B-cells, and dendritic cells, which is overexpressed in certain tumor cell types.
A covalent conjugate of recombinant human interleukin-10 (IL-10) and polyethylene glycol (PEG), with potential anti-fibrotic, anti-inflammatory, immunomodulating and antineoplastic activities. Upon subcutaneous administration, pegylated recombinant human interleukin-10 AM0010 may activate cell-mediated immunity against cancer cells by stimulating the differentiation and expansion of tumor specific cytotoxic CD8+ T cells. This agent may also lower serum cholesterol levels and reduce atherosclerotic plaques by inhibiting the synthesis of pro-inflammatory cytokines, such as Interferon-gamma, IL-2, IL-3, TNF-alpha, and GM-CSF. The PEG moiety inhibits proteolytic breakdown and clearance of AM0010, which prolongs its half-life, extends the duration of its therapeutic effects and allows less frequent dosing.
A preparation of cytotoxic, autologous lymphoid effector cells specifically targeted towards tumor cells, with potential immunomodulating and antineoplastic activities. The autologous lymphoid effector cells are prepared by drawing a blood sample containing the required precursors for CD4+ helper T-cells, CD8+ cytotoxic T-cells, and natural killer (NK) cells from a cancer patient. The precursor cells are activated, selected and expanded to generate mature autologous lymphoid effector cells with the potential for enhanced tumor recognition. Upon readministration into the patient, the autologous lymphoid effector cells may induce both humoral and cellular immune responses against tumor cells. This may result in the immune-mediated inhibition of tumor cell proliferation, which leads to tumor cell death.
A live-attenuated, double-deleted strain of the Gram-positive bacterium Listeria monocytogenes (Lm) encoding a mutant form of the tumor associated antigens, epidermal growth factor receptor (EGFRvIII) and the cancer/testis antigen NY-ESO-1, with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, live-attenuated Listeria monocytogenes encoding EGFRvIII-NY-ESO-1 vaccine targets dendritic cells and expresses EGFRvIII and NY-ESO-1. This promotes both a potent innate immune response and an adaptive immune response involving the recruitment and activation of T lymphocytes against EGFRvIII and NY-ESO-1-expressing tumor cells, which results in tumor cell lysis.
A glutathione (GSH) pegylated, liposome-encapsulated preparation of the hydrochloride salt form of the anthracycline antineoplastic antibiotic doxorubicin, with potential anetineoplastic activity. Upon administration, the glutathione pegylated liposomal formulation 2B3-101 specifically delivers doxorubicin into the brain. Doxorubicin intercalates between DNA base pairs and interferes with topoisomerase II activity, which inhibits both DNA replication and RNA synthesis, resulting in cancer cell death and tumor regression. Doxorubicin also generates reactive oxygen species, which causes cell membrane lipid peroxidation leading to cytotoxicity. The pegylated liposomal delivery of doxorubicin improves drug penetration into tumors and prolongs circulation time, thereby increasing doxorubicin's efficacy and decreasing its toxicity. Conjugation of GSH to the PEG molecules directs the liposomes to the GSH transporters on the blood brain barrier (BBB) and improves the delivery of doxorubicin into the brain.
The sodium salt form of cridanimod, a small molecule that can increase progesterone receptor (PR) expression, with potential antineoplastic adjuvant activity. Upon intramuscular administration, cridanimod is able to induce the expression of PR in endometrial cancer. This could increase the sensitivity of endometrial cancer cells to progestin monotherapy. In combination with a progestin, cancer cells could be eradicated through increased PR-mediated signaling, leading to an inhibition of luteinizing hormone (LH) release from the pituitary gland, via a negative feedback mechanism, and, eventually, an inhibition of estrogen release from the ovaries. This leads to an inhibition of cellular growth in estrogen-dependent tumor cells. In addition, this agent is able to increase the production and release of interferon (IFN) alpha and beta. PR is often downregulated in endometrial cancer and makes it resistant to progestin-mediated hormone therapy.
A radioconjugate composed of a derivative of the multi-targeted kinase inhibitor dasatinib conjugated to the radioisotope fluorine F 18, with potential imaging activity during positron emission tomography (PET). Upon administration of fluorine F 18 SKI-249380, the SKI-249380 moiety targets and binds to Bcr/Abl, SRC-family protein-tyrosine kinases, c-Kit and platelet-derived growth factor receptor (PDGFR). Upon binding, the fluorine F 18 moiety allows PET imaging of tumor cells and can be used as a tracer for the biodistribution of dasatinib.
A radioconjugate comprised of the orally available reversible 20S proteasome inhibitor ixazomib and labeled with the isotope carbon C 14. Upon administration, the ixazomib moiety hydrolyzes and generates its active form, MLN2238, which inhibits the activity of the 20S catalytic core subunit of the proteasome. This blocks the targeted proteolysis normally performed by the proteasome, which results in an accumulation of unwanted or misfolded proteins. The accumulation of protein may disrupt various cell signaling pathways, induce apoptosis, and inhibit tumor growth. In addition, this agent targets tumor suppressor microRNA-33b (miR-33b). Labeling with the radioactive tracer carbon C 14 allows for evaluation of ixazomib's absorption, distribution, metabolism and excretion (ADME).
Classification of glioblastoma into molecular subtypes as defined by gene expression profiling.
An orally available fumarate salt form of CFI-400945, a polo-like kinase 4 (PLK4) inhibitor with potential antineoplastic activity. Upon oral administration, polo-like kinase 4 inhibitor CFI-400945 selectively inhibits PLK4, which results in the disruption of mitosis and the induction of apoptosis. PLK4 inhibition also prevents cell division and inhibits proliferation of PLK4-overexpressing tumor cells. PLK4, a member of the polo family of serine/threonine kinases overexpressed in a variety of cancer cell types, plays a crucial role in the regulation of centriole duplication during the cell cycle.
Painful red or purple patches, edematous plaques or blisters on the hands, feet, extremities or intertriginous regions; the onset can occur days to months after receiving chemotherapy.
A dietary supplement containing coffee, with potential gastrointestinal (GI) tract stimulating activity. Following consumption of the dietary supplement, the coffee may both stimulate peristalsis and may increase bowel movement. The supplement also may also stimulate the central nervous system, suppress appetite and cause weight loss.
The time when regular uterine contractions began that resulted in labor with or without the use of pharmacological and/or mechanical interventions. (reVITALize)
A change in the amino acid residue at position 842 in the platelet-derived growth factor receptor alpha protein where aspartic acid has been replaced by valine.
Patient did not like the question content.
A microscopic finding indicating the presence of scattered islands of pathologic processes in a tissue sample. The pathologic processes may refer to various abnormalities, including the presence of islands of malignant cells, presence of necrotic foci, and presence of islands of connective tissue that lack fibers.
A molecular subtype of glioblastoma characterized by lack of p53 mutations, chromosome 7 amplifications or deletions, and high levels of EGFR amplification.
Any monoclonal antibody directed against the cell surface glycoprotein CD6, regardless of the antibody type.
Any tumor lesion other than the largest tumor lesion targeted by therapy.
Unexpected death of a child over one year of age, which remains unexplained when all known and possible causes of death have been ruled out.
An indication or description that a subject characteristics test has occurred.
A microscopic finding indicating the presence or absence of loops forming networks in uveal melanoma.
A complex substitution where the nucleotide sequence at positions 1848 and 1849 of the coding sequence of the JAK2 gene has changed from thymine-guanine to cytosine-thymine.
A nutritional supplement drink containing 12.5% carbohydrates, which may enhance recovery following gastrointestinal (GI) surgery. Oral intake of the carbohydrate drink before surgery may prevent insulin resistance and associated hyperglycemia. It may also maintain adequate protein balance and muscle function. Ultimately, giving carbohydrates immediately before surgery may improve overall recovery time and return of GI function. It may also decrease muscle loss.
An antagonist of the C-X-C chemokine receptor type 4 (CXCR4). CXCR4, which belongs to the G protein-coupled receptor (GPCR) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types.
The finding of a growth smaller than 5 mm x 5 mm that was not present at the previous evaluation. Its presence does not indicate disease progession but precludes a determination of complete remission based on the modified overall immune related response criteria.
A change in the amino acid residue at position 375 in the fibroblast growth factor receptor 2 protein where tyrosine has been replaced by cysteine.
The juice extracted from the mature sprouts of wheatgrass, Triticum aestivum, which is a member of the Poaceae family, with potential anti-inflammatory, immunomodulating and chemopreventive activities. Wheatgrass juice contains many vitamins, including A, B vitamins, C and E, minerals, including selenium, iron, magnesium, calcium, manganese, copper and zinc, amino acids, chlorophyll and a number of antioxidant enzymes, including superoxide dismutase and cytochrome oxidase. Although the exact mechanism(s) of action through which wheatgrass juice exerts its effect(s) has yet to be fully elucidated, the components in the juice may scavenge free radicals, reduce chemotherapy-induced myelotoxicity, neutralize toxins and carcinogens and modulate the levels of certain pro-inflammatory cytokines, such as interleukin (IL)- 6, IL-8, IL-10 and IL-12.
An electrocardiographic finding of normal sinus rhythm coexisting with a regular ectopic ventricular rhythm.
An electrocardiographic finding of a normal QRS followed by a premature ventricular contraction; a rhythmic pairing of normal and atypical beats originating in the ventricles in a 1-1 ratio.
An anomaly of the U wave of the electrocardiogram (EKG). The U wave is a small (0.5 mm) deflection immediately following the T wave, usually in the same direction as the T wave. It is best seen in leads V2 and V3.
A carcinosarcoma of the uterus characterized by the presence of sarcomatous elements that arise from the tissues of the uterus.
A carcinosarcoma of the uterus characterized by the presence of sarcomatous elements composed of tissues that are not found in the uterus (e.g., bone, cartilage, skeletal muscle).
Narrowing of the luminal diameter of one or both ureters due to extrinsic pressure.
Indicates that a phlebotomist was unable to find or penetrate a blood vessel or was unable to acquire a blood sample following a successful vein stick.
Indicates that an individual is unable to self-collect a urine specimen.
Unable to meet the requirements of an individual's disability or language.
Blockage of blood flow in the umbilical vessels.
An autophagosome-enriched cancer vaccine composed of short lived proteins (SLiPs) and defective ribosomal products (DRiPs) derived from tumor cells, with potential immunostimulating and antineoplastic activities. The Dribbles are DriPs- and SLiPs-filled autophagosomes that are made by treating cancer cells with both a proteasome inhibitor, to prevent protein degradation, and an autophagy inducer, which causes the accumulation of DriPs, SLiPs, and their immunogenic fragments. Upon administration of a Dribbles vaccine, the proteins or antigen fragments in Dribbles may stimulate the immune system to mount cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte responses against the cancer-associated antigens (TAAs).
A water soluble analog of the diterpenoid triepoxide triptolide isolated from the Chinese herb Tripterygium wilfordii Hook.f., with potential antineoplastic activity. Upon intravenous administration, the triptolide analog inhibits heat shock protein 70 (HSP70) and prevents HSP70-mediated inhibition of apoptosis. This leads to both the induction of apoptosis and a reduction of cancer cell growth. HSP70, a molecular chaperone upregulated in various cancer cells, plays a key role in the inhibition of caspase-dependent and -independent apoptosis.
Trial of labor in a woman with a previous cesarean delivery regardless of ultimate route of delivery.
A morphologic finding indicating the presence of an epithelial infiltrate resembling the cells of the transition zone of the prostate gland.
A common, self-limiting thyroid disorder seen in preterm infants that is characterized by abnormally low serum levels of thyroxine and free thyroxine with normal serum levels of thyroid stimulating hormone.
A transdermal formulation containing 4-hydroxytestosterone (4-OHT), a steroidal aromatase inhibitor (AI) and androgen receptor (AR) antagonist, with potential antineoplastic activity. 4-OHT is largely converted into 4-hydroxyandrostenedione (4-OHA) and irreversibly binds to and inhibits aromatase, thereby blocking the conversion of androstenedione to estrone, and testosterone to estradiol. This may inhibit tumor cell proliferation in estrogen-dependent tumor cells. In addition, 4-OHT binds to the AR and may inhibit AR-mediated tumor cell growth. Aromatase, a cytochrome P-450 enzyme, is overexpressed in a variety of cancer cells; it plays a key role in estrogen biosynthesis. Compared to oral 4-OHT, the transdermal formulation allows for continuous release of 4-OHT into the bloodstream and prevents first pass metabolism by the liver.
A colon that is longer than a normal colon, with additional bends and twists.
A topical formulation containing the macrolide sirolimus (rapamycin), which is produced by the organism Streptomyces hygroscopicus, with potential anti-proliferative activity. Upon application of topical sirolimus, this agent migrates into the skin and is internalized by the affected cells. In turn, sirolimus binds to the immunophilin FK binding protein-12 (FKBP-12) and forms a sirolimus:FKBP-12 complex. This complex binds to and inhibits the activity of the serine/threonine kinase mammalian target of rapamycin (mTOR). It also decreases the production of vascular endothelial growth factor (VEGF) and results in the suppression of cellular proliferation.
A preparation of tumor infiltrating lymphocytes (TILs) that are transduced with a retroviral vector encoding a gene for a dominant-negative form of the transforming growth factor beta (TGFb) receptor, TGFbDNRII, with potential immunomodulating activity. Upon administration, the TGFbDNRII-transduced autologous TILs recognize and kill tumor cells. The expression of TGFbDNRII allows for the TILs to be resistant to TGF-b-mediated inhibition of T cell proliferation and activation, which allows optimal TIL activity. The immunosuppressant TGF-b is produced by tumor cells and plays a key role in the repression of the immune system.
A red, edematous ring skin finding that may have a central dusky disk and an erythematous halo.
An electrocardiographic finding of abnormally rapid heart rate. Thresholds for different age, gender, and patient populations exist.
A translocation between chromosome 9 and chromosome 11.
Autologous CD4 positive T-lymphocytes engineered to express the chimeric antigen receptor (CAR) T1E28z containing the ErbB ligand, T1E, fused to the hinge region, transmembrane domain and endodomain of CD28 and the CD3zeta endodomain, with potential immunomodulating and antineoplastic activities. T1E, a chimeric polypeptide containing the N-terminus of human transforming growth factor (TGF)-alpha fused to the C-terminus of epidermal growth factor (EGF), binds to ErbB1 homodimers and heterodimers as well as ErbB2/3 heterodimers, but not to ErbB2 or erbB3 alone. Upon intratumoral administration, the promiscuous ErbB ligand T1E of the T1E28z CAR-expressing autologous CD4-positive T lymphocytes binds to the specific ErbB homo- and heterodimers on tumor cells. This induces selective toxicity in ErbB-expressing tumor cells resulting in tumor cell lysis. ErbB1, ErbB2 and ErbB3, members of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, are frequently overexpressed in solid tumors and play key roles in tumor cell proliferation and tumor angiogenesis.
A chromosomal translocation between 14q32 and 16q23. This rearrangement is associated with MAF protein overexpression in plasma cell myeloma.
Sustained donor-derived neutrophil recovery with achievement of donor chimerism equal or greater than 90%.
Sustained donor-derived neutrophil recovery with achievement of donor chimerism equal or greater than 90% at day 100.
An autologous dendritic cell (DC) vaccine loaded with tumor-associated antigens (TAAs) derived from survivin, p53 and human epidermal growth factor receptor 2 (HER2 or ERBB2), with immunostimulating and antineoplastic activities. Upon administration, this DC vaccine may elicit a potent cytotoxic T-cell (CTL) response against tumor cells expressing these TAAs, resulting in tumor cell death. Survivin, p53 and HER2 are essential in neoplastic growth, and are considered to be universal tumor antigens.
An orally available, stable powder formulation composed of sulforaphane, a naturally-occurring phytochemical belonging to the class of isothiocyanates, encapsulated within alpha-cyclodextrin, with chemopreventive activity. Upon administration of sulforaphane/alpha-cyclodextrin complex SFX-01, sulforaphane activates the transcription factor NF-E2-related factor 2 (Nrf2; NFE2L2), a member of the basic leucine zipper family, which binds to and activates antioxidant-response elements (AREs). Subsequently, activated AREs mediate the transcription of various cytoprotective genes and antioxidant enzymes, particularly phase II detoxification enzymes, such as glutathione-S-transferase and quinone oxidoreductase, resulting in the detoxification of highly reactive carcinogens. Cyclodextrin is able to prevent sulforaphane's rapid breakdown, which improves its stability and half-life.
Preterm birth from 20 weeks to 36 weeks, 6 days of gestation associated with one of the following: classic preterm labor or preterm premature rupture of membranes.
An herbal-based nutritional supplement containing the leaf sheaths of the plant Sorghum bicolor, with potential antioxidant, anti-inflammatory, chemopreventive and immunomodulating activities. Sorghum bicolor supplement contains various phytochemicals, including phenolic acids and polyphenols such as proanthocyanidins. Sorghum bicolor supplement is particularly rich in 3-deoxyanthocyanins, such as luteolinidin and apigeninidin, and appears to induce apoptosis and inhibit cell proliferation in cancer cells through the stimulation of various apoptosis promoter genes and the downregulation of certain apoptosis inhibitor genes. In addition, due to the strong antioxidant nature of the phytochemicals, these compounds are able to scavenge free radicals and prevent tissue damage. Also, intake of this supplement modulates the immune system by both increasing the activity of natural killer (NK) cells and initiating the activation of macrophages.
A response indicating that something happens or happened some of the time.
The hydrochloride salt form of simmitecan, an ester prodrug of chimmitecan, a 9-alkyl substituted camptothecin derivative with potential antineoplastc activity. Upon intravenous administration, simmitecan is hydrolyzed by carboxylesterase and the activated form, chimmitecan, is produced. Chimmitecan inhibits topoisomerase I, stabilizes covalent topoisomerase I-DNA complexes, and inhibits the religation of topoisomerase I-mediated single-strand DNA breaks. Futhermore, the covalent topoisomerase I-DNA complexes interfere and block the DNA replication machinery, resulting in the production of potentially lethal double-strand DNA breaks. This leads to an inhibition of DNA replication and the induction of apoptosis. The modification at position 9 yields improved cytotoxicity compared to some other camptothecin analogues.
A large intestinal glandular mucosal lesion in the mouse characterized by epithelial infoldings and ectopic crypt formation.
An orally bioavailable ditosilate salt form of selatinib, an analog of the quinazoline lapatinib and dual inhibitor of epidermal growth factor receptor (EGFR) and Human Epidermal Growth Factor Receptor 2 (ErbB-2 or HER-2), with potential antineoplastic activity. Upon administration, selatinib reversibly blocks phosphorylation of both EGFR and ErbB2, thereby suppressing tumor growth in EGFR/ErbB-2-overexpressing tumor cells. The tyrosine kinases EGFR and ErbB2 have been implicated in the growth of various tumor types.
Loss of donor hematopoietic cells following initial engraftment.
An infrequent malignant neoplasm that occurs during childhood.
Injury resulting from exposure to ionizing radiation.
An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula is shortened. Thresholds for different age, gender, and patient populations exist. (CDISC)
An electrocardiographic finding in which the QT interval corrected for heart rate using Fridericia's formula is prolonged. Thresholds for different age, gender, and patient populations exist.
An electrocardiographic finding in which the QT interval corrected for heart rate using Bazett's formula is shortened. Thresholds for different age, gender, and patient populations exist. (CDISC)
An electrocardiographic finding in which the QT interval corrected for heart rate using Bazett's formula is prolonged. Thresholds for different age, gender, and patient populations exist. (CDISC)
An orally bioavailable, dual kinase inhibitor of the epidermal growth factor receptor (EGFR or HER-1) and the human epidermal growth factor receptor 2 (ErbB2 or HER-2), with potential antineoplastic activity. Upon oral administration, pyrotinib binds to and inhibits both EGFR and HER2, which may result in the inhibition of tumor growth and angiogenesis, and tumor regression in EGFR/HER2-expressing tumor cells. EGFR and HER2 are receptor tyrosine kinases that are upregulated in various tumor cell types and play major roles in tumor cell proliferation and tumor vascularization.
A diffuse or generalized outbreak of numerous pustules.
Abnormally absent or incomplete sexual development.
A prostate cancer vaccine containing prostate specific antigen (PSA) combined with the cytokines, interleukin-2 (IL-2) and granulocyte macrophage-colony-stimulating factor (GM-CSF), with potential antineoplastic activity. Upon intradermal vaccination, PSA/IL-2/GM-CSF vaccine may activate the immune system to induce a cytotoxic T-cell (CTL) response against prostate cancer cells expressing this antigen, thereby decreasing tumor cell growth. PSA, a glycoprotein secreted by prostatic epithelial and ductal cells, is overexpressed by prostate cancer cells. IL-2 stimulates natural killer (NK) cells and cytotoxic T-cells against the PSA-expressing tumor cells. GM-CSF promotes antigen presentation to dendritic cells and further stimulates a tumor-specific cytotoxic T-lymphocyte (CTL) response.
Malfunction of a surgically-placed cardiac valve related to the valve itself or the area around the valve.
A molecular subtype of glioblastoma that is associated with younger age at presentation and is characterized by p53 mutations and PDGFRa amplifications.
An oral solution containing a mixture of proteinases, which are produced by Streptomyces griseus, with mucolytic activity and potential diagnostic applications. Upon oral administration, pronase is able to cleave peptide chains of polypeptides into individual amino acids, thereby dissolving mucus. The removal of mucus may improve the visibility of parts of the digestive tract, such as the esophagus and the stomach, during endoscopy. Pre-treatment with pronase before endoscopic examination may help in the detection of certain cancers, such as esophageal and gastric cancer.
Abnormally low levels of parathyroid hormone due to a disorder originating within the parathyroid glands.
Failure of initial engraftment of donor hematopoietic cells.
A microscopic finding indicating the presence of patterns formed by malignant cells outside the blood vessel circulation in uveal melanoma. The patterns are detectable using PAS stain without counterstaining with hematoxylin.
Nausea and/or vomiting co-occurring with pregnancy.
Diabetes diagnosed before current pregnancy. (reVITALize)
Protrusion of the uterine fundus through the cervix when the placenta fails to detach from the uterus as it exits.
Severe loss of blood pressure leading to inadequate tissue perfusion after the delivery of the fetus.
Presence of a blood clot in the maternal vascular system which originated from a distant site during the postpartum period.
Presence of bacterially-infected tissue in the maternal vascular system which originated from a distant site during the postpartum period.
Presence of a large air bubble in the maternal vascular system which originated from a distant site during the postpartum period.
A morphologic finding indicating the presence of a malignant cellular infiltrate with poorly defined glands in a tissue sample.
A commercial combination preparation that contains an adhesive polycarbophil polymer, which is used for vaginal lubrication. Polycarbophil is an insoluble compound that absorbs water and, after topical administration, adheres to vaginal epithelial cells. As a result, it helps both moisturize vaginal tissue and relieve the discomfort that is associated with vaginal dryness.
A pathologic finding indicating the extent of visceral pleural invasion by a malignant neoplasm.
A vaccine composed of a phosphorylated peptide from the tumor associated antigen insulin receptor substrate-2 (IRS2) and a tetanus-derived peptide, with potential immunomodulating and antineoplastic activities. Upon administration of pIRS2 phosphopeptide-tetanus peptide vaccine, the pIRS2 phosphopeptide may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against phosphopeptide-containing tumor cells. The tetanus peptide serves as an immunoadjuvant and induces a helper T-cell response which may help stimulate an immune response against the pIRS2-expressing melanoma tumor cells. IRS2 is upregulated in a variety of cancer cells.
A change in the amino acid residue at position 1047 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where histidine has been replaced by another amino acid.
A change in the amino acid residue at position 545 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by another amino acid.
A change in the amino acid residue at position 542 in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha isoform protein where glutamic acid has been replaced by another amino acid.
An observation of the pharyngeal residue remaining after an individual swallows.
A peptide vaccine derived from cytomegalovirus (CMV) antigens with potential immunostimulating activity. Intradermal administration of the PEP-CMV vaccine may stimulate the immune system to mount a specific helper and cytotoxic T-lymphocyte (CTL) response against CMV-infected tumor cells. Infection with the herpesvirus CMV may play a significant role in tumor cell initiation and progression as well as chemoresistance.
A disorder characterized by an electrocardiographic finding of three or more consecutive complexes of ventricular origin that was not present at birth in an individual under age 21. The QRS complexes are wide and have an abnormal morphology.
A variation in the amino acid sequence for the platelet-derived growth factor receptor alpha protein.
A nucleotide substitution at position 2525 of the coding sequence of the PDGFRA gene where adenine has been mutated to thymine.
A vaccine composed of phosphorylated peptides from the tumor associated antigens breast cancer anti-estrogen resistance-3 (BCAR3) and insulin receptor substrate-2 (IRS2) and a tetanus-derived peptide, with potential immunomodulating and antineoplastic activities. Upon administration of pBCAR3/pIRS2 phosphopeptide-tetanus peptide vaccine, the pBCAR3/pIRS2 phosphopeptide may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing either phosphopeptide. The tetanus peptide serves as an immunoadjuvant and induces a helper T-cell response which may help stimulate an immune response against pBCAR3 and pIRS2-expressing melanoma tumor cells. BCAR3 and IRS2 are upregulated in a variety of cancer cells.
A vaccine composed of a phosphorylated peptide from the tumor associated antigen breast cancer anti-estrogen resistance-3 (BCAR3) and a tetanus-derived peptide, with potential immunomodulating and antineoplastic activities. Upon administration of pBCAR3 phosphopeptide-tetanus peptide vaccine, the pBCAR3 phosphopeptide may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against phosphopeptide-containing tumor cells. The tetanus peptide serves as an immunoadjuvant and induces a helper T-cell response, which may help stimulate an immune response against the pBCAR3-expressing melanoma tumor cells. BCAR3 is upregulated in a variety of cancer cells.
A cancer vaccine consisting of autologous dendritic cells (DCs) loaded with autologous, lethally irradiated cancer cells and mixed with the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), with potential immunostimulatory and antineoplastic activities. Upon vaccination, ovapuldencel-T may stimulate the immune system to exert a cytotoxic T-lymphocyte (CTL) immune response against the repertoire of tumor associated antigens (TAAs) found in the irradiated cancer cells. GM-CSF enhances the activation of dendritic cells (DCs) and promotes antigen presentation to both B- and T-lymphocytes.
A combination formulation composed of a capsule containing the taxane compound paclitaxel and a tablet containing the multidrug resistance (MDR) efflux pump P-glycoprotein (P-gp) inhibitor HM30181A, with potential antineoplastic activity. Upon oral administration of oraxol, the HM30181A moiety binds to and inhibits P-gp, which prevents P-gp-mediated efflux of paclitaxel, therefore enhancing its oral bioavailability. In turn, paclitaxel binds to and stabilizes microtubules, preventing their depolymerization, which results in the inhibition of cellular motility, mitosis, and replication. Altogether, this may result in greater intracellular concentration of paclitaxel, and enhanced cytotoxicity against tumor cells, when compared to the administration of paclitaxel alone. P-gp, encoded by the MDR-1 gene, is a member of the ATP-binding cassette (ABC) superfamily of transmembrane transporters; it prevents the intestinal uptake and intracellular accumulation of various cytotoxic agents.
An ICP34.5-, ICP47-deleted, oncolytic herpes simplex type-1 virus (HSV-1) isolated from the mouth of an HSV-1-infected patient of Chinese Han ethnicity, and encoding the immunostimulating factor cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) with potential immunostimulating and antineoplastic activities. Upon administration, the recombinant human GM-CSF HSV-1 selectively infects and replicates in tumor cells, thereby inducing tumor cell lysis. In addition, GM-CSF attracts dendritic cells (DCs) and may stimulate a cytotoxic T cell response against tumor cells, which results in immune-mediated tumor cell death. Deletion of the gene encoding for ICP34.5 provides tumor selectivity and prevents replication in healthy cells. As ICP47 blocks antigen presentation in HSV-infected cells, deletion of this gene may induce a more potent antitumor immune response in the tumor cells. Additionally, deletion of ICP47 causes increased expression of the HSV US11 gene and allows US11 to be expressed as an immediate early and not a late gene. This further enhances the degree of viral replication and oncolysis of tumor cells. Interruption of the ICP6 gene, which encodes the large subunit of the viral ribonucleotide reductase, in the viral vector also enhances selective replication in tumor cells.
Bone marrow-derived autologous mesenchymal stem cells (MSCs) infected with the oncolytic, replication-competent adenovirus ICOVIR5, with potential antineoplastic activity. Upon infusion of the oncolytic adenovirus ICOVIR5-infected autologous MSCs, these cells target the adenovirus to tumors. The oncolytic virus then selectively transfects and replicates in the tumor cells causing a direct cytotoxic effect and lysis of the tumor cells. In addition, the viral infection may stimulate an immune response against the virally-infected tumor cells. This may lead to an inhibition of cancer cell proliferation. ICOVIR-5, a virus derived from wild-type human adenovirus serotype 5 (Had5), has been modified to selectively replicate in tumor cells that have a deregulated retinoblastoma/E2F pathway.
An injectable, isotonic, nutritional lipid emulsion composed of approximately 80% refined olive oil and 20% refined soybean oil, used for parenteral nutrition. The olive oil/soya oil/egg lecithin emulsion provides about 15% of saturated fatty acids (SFA), 65% of mono-unsaturated fatty acids (MUFA) and 20% of essential poly-unsaturated fatty acids (EPUFA). Upon parenteral administration, the emulsion supplies calories, for energy, and essential fatty acids that can be incorporated into cell membranes. The fatty acids may decrease the production of certain pro-inflammatory cytokines, including interleukin 1 (IL-1), IL-6 and tumor necrosis factor (TNF). In addition to olive oil and soya oil, this lipid emulsion contains egg lecithin and provides phosphorus and choline, which are needed to maintain cell membrane integrity.
A capsule containing an extract of olive oil, rich in polyphenols, and curcumin, the polyphenol derived from the plant Curcuma longa, also known as turmeric, with potential anti-neoplastic, -angiogenic, -inflammatory, -oxidant and chemopreventive activities. The olive oil extract/curcumin-based capsule is rich in phytonutrients, especially polyphenols. Upon oral administration, the polyphenols, and other active ingredients in this supplement may exert anti-inflammatory activity by decreasing the production of inflammation mediators, such as TNF-alpha, interleukin (IL) 1-beta, IL-6, IL-10, interferon gamma, thromboxane B2, and leukotriene B4. They also inhibit a variety of pro-inflammatory enzymes, such as cyclooxygenase 1 (COX-1) and COX-2, block the formation of reactive-oxygen species and neutralize free radicals. In addition, curcumin and some other polyphenols disrupt cell signal transduction pathways involved in carcinogenesis. Specifically, curcumin inhibits cell invasion by inhibiting matrix metalloproteinase-9 (MMP-9) expression by suppressing NF-kB and AP-1 activation.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with a peptide derived from the tumor associated antigen human cancer-testis antigen NY-ESO-1 (NY-ESO-1(157-165)), with potential immunostimulatory and antineoplastic activities. Upon administration, the NY-ESO-1(157-165) peptide-pulsed autologous dendritic cell vaccine may stimulate the immune system to mount both an anti-tumoral cytotoxic T-lymphocyte (CTL)- and an antibody-mediated immune response against NY-ESO-1-expressing tumor cells, which may result in tumor cell lysis. NY-ESO-1 is expressed both in normal testes and on the surfaces of various tumor cells, and plays a key role in tumor cell proliferation and survival.
The last documented cervical dilation, in centimeters, when the provider orders admission. (reVITALize)
A change in the amino acid residue at position 61 in the GTPase NRas protein where glutamine has been replaced by another amino acid.
A change in the amino acid residue at position 13 in the GTPase NRas protein where glycine has been replaced by another amino acid.
A change in the amino acid residue at position 12 in the GTPase NRas protein where glycine has been replaced by another amino acid.
A response indicating that an individual does not feel limited at all.
The mother develops antibodies against red blood cell non-Rhesus antigens. This may lead to potential fetal adverse outcomes such as anemia.
A scar/healing of the myometrium that occurs after uterine injury or after non-cesarean surgery.
An electrocardiographic finding in leads V1 or V2 of an initial R wave duration greater than or equal to 40 ms, R wave greater than S wave, and upright T wave, which is suggestive of myocardial infarction of the posterior wall of the left ventricle, and which is new compared to prior ECGs. Evidence of inferior or lateral myocardial infarction is usually also present. (CDISC)
A molecular subtype of glioblastoma characterized by the expression of the neural markers NEFL, GABRA1, SYT1, and SLC12A5.
A sterile combination preparationscontaining neomycin sulfate, polymyxin B sulfate and bacitracin zinc, as the main active ingredients, for ophthalmic treatments. Polymyxin B sulfate, a polypeptide produced by Bacillus polymyxa, binds to the negatively charged phospholipids in the cell membrane, thereby altering the permeability of the bacterial cytoplasmic membrane. Neomycin sulfate, an aminoglycoside antibiotic, irreversibly binds to the bacterial 30S subunit proteins and 16S rRNA of ribosome, thereby causing misreading and inhibiting protein synthesis which results in bactericidal effect.
A combination preparation containing the polypeptide antibiotic polymyxin b, the aminoglycoside antibiotic neomycin, the glucocorticoid hydrocortisone and, in some formulations, the antibiotic bacitracin zinc with antibacterial and anti-inflammatory activities. Polymyxin B, neomycin and bacitracin zinc exert antibacterial effects through a cationic detergent-like action on cell membranes, inhibition of protein synthesis, and inhibition of peptidoglycan synthesis, respectively. Hydrocortisone initially binds to the cytoplasmic glucocorticoid receptor; then the receptor-ligand complex is translocated to the nucleus where it initiates the transcription of genes encoding for anti-inflammatory mediators, such as cytokines and lipocortins.
A peptide-based melanoma cancer vaccine consisting of neoantigens and peptides derived from patient-specific melanoma immunogenic epitopes, combined with the immunostimulant poly-ICLC with potential immunomodulating and antineoplastic activities. Vaccination with the neoantigen-based melanoma vaccine stimulates the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis. The adjuvant poly-ICLC, composed of double-stranded RNA molecules of polyinosinic-polycytidylic acid stabilized with poly L-lysine in carboxymethylcellulose, is a ligand for toll-like receptor-3 (TLR3) and induces the release of cytokines which may help to boost the immune response against the selected neoantigens.
A chromosomal abnormality in which there are less than thirty chromosomes in a cell.
The powder form of the cooked navy bean with potential antioxidant and chemopreventive activities. Navy beans are rich in fiber, minerals, vitamins, and phytochemicals such as flavonoids and phytosterols. They appear to prevent carcinogenesis by inducing tumor cell apoptosis. Intake of navy bean powder may have a beneficial effect on intestinal microflora.
Nausea and vomiting occurring during the first 24 hours following chemotherapy.
A lesion having the shape of a mushroom.
A vaccine consisting of an inactivated, Modified Vaccinia Ankara (MVA) viral vector encoding three herpes virus cytomegalovirus (CMV) tumor-associated antigens (TAAs), including UL83 (pp65), UL123 (IE1) and UL122 (IE2), with potential immunostimulating activity. The viral peptides expressed after administration of the multi-peptide CMV-MVA vaccine, may stimulate the immune system to mount both cytotoxic T-lymphocyte (CTL) and helper T-cell responses against CMV-infected cells. This results in cell lysis and prevents viral replication and the development of CMV disease. This vaccine also provides active immunization and protective immunity against CMV infection in CMV-negative patients. CMV infection can cause serious complications in patients receiving either allogeneic hematopoietic cell transplants (HCT) or solid organ transplants.
Precancerous dysplastic lesions depleted of mucin in the colonic mucosa of the mouse.
A response indicating that something happens or happened most of the time.
The evaluation of the antitumor response shows that the sum of the longest diameters of target and new measurable lesions do not meet the criteria for complete remission, partial response (compared to baseline) or progressive disease (compared to nadir).
The evaluation of the antitumor response shows that the sum of the longest diameters of target and new measurable lesions increases by at least 20% (compared to nadir), and is confirmed by repeated, consecutive observations at least 4 weeks (normally done at 6 weeks) from the date first documented.
The evaluation of the antitumor response shows that the sum of the longest diameters of target and new measurable lesions has decreased by at least 30%.
The evaluation of the antitumor response shows a complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also have a reduction in short axis diameter to 10 mm.
A baseline fetal heart rate with a detectable amplitude range that is greater than or equal to 6 but less than or equal to 25 beats per minute.
A chromosomal rearrangement where exons 5 through 11 or 5 through 12 of the MLL gene are duplicated and inserted upstream of exon 4 of the gene. This duplication results in transcripts and proteins that have the N-terminal region, which contains the AT hook DNA-binding motifs, and the transcriptional repression domain duplicated. This mutation is associated with myelodysplastic syndrome (MDS) and susceptibility of MDS progression to acute myeloid leukemia.
An intraductal papillary-mucinous neoplasm of the pancreas that arises primarily from the main pancreatic duct and extends to the branch ducts.
Patients in whom some, but not all, the criteria for partial response are fulfilled are classified as minimal response (MR), provided the remaining criteria satisfy the requirements for minimal response. MR requires all of the following: 1. 25-49% reduction in the level of the serum monoclonal paraprotein maintained for a minimum of 6 weeks; 2. 50-89% reduction in 24 h urinary light chain excretion, which still exceeds 200 mg/24 h, maintained for a minimum of 6 weeks; 3. for patients with non-secretory myeloma only, 25-49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks; 4. 25-49% reduction in the size of soft tissue plasmacytomas (by radiography or clinical examination); 5. no increase in size or number of lytic bone lesions (development of a compression fracture does not exclude response) (adapted from National Comprehensive Cancer Network).
A numerical chromosomal abnormality characterized by the presence of copy number variations in less than five percent of chromosomal arms.
An oromucosal solution containing the maleate salt form of midazolam, a short-acting benzodiazepine derivative, with anxiolytic, hypnotic, anticonvulsant and sedative activities. Upon administration of the solution into the buccal cavity, midazolam exerts its effect by binding to the benzodiazepine receptor at the gamma-aminobutyric acid (GABA) receptor-chloride ionophore complex in the central nervous system (CNS). This leads to an increase in the permeability of chloride channels, membrane hyperpolarization and enhances the inhibitory effect of GABA in the CNS. Midazolam may also interfere with the reuptake of GABA, thereby causing accumulation of GABA in the synaptic cleft. The oromucosal formulation facilitates administration to patients that are unable to swallow. The ethanol in this formulation improves the buccal absorption of midazolam.
A carcinoma that arises from the intestinal tract of the mouse and has spread to other anatomic sites.
A molecular subtype of glioblastoma characterized by the presence of NF1 mutations.
The last recorded maternal weight prior to birth minus the last recorded weight immediately prior to pregnancy. (reVITALize)
A chromosomal abnormality in which a near-haploid cell line is masked by a co-existing hyperdiploid line.
The tumor shows lymphogenous or hematogenous metastasis to distant sites.
The tumor shows metastasis throughout the pleural and/or pericardial spaces.
The tumor shows invasion into the neighboring tissues and organs of the lower neck or upper chest.
The tumor shows invasion through the capsule and into the surrounding fatty tissue.
The tumor shows microscopic invasion into the capsule.
Human CD8-positive T-lymphocytes that are engineered to recognize melanoma tumor associated antigen MART-1 (Melanoma Antigen Recognized by T cells, also called Melan-A) in a human leukocyte antigen (HLA)-A2-restricted manner, with potential antineoplastic activity. Human peripheral blood lymphocytes (PBLs) are isolated from a melanoma patient, exposed to the MART-1:27-35(27L) peptide and MART-1 specific T-lymphocytes are isolated and expanded. Upon infusion, these lymphocytes recognize and exert a cytotoxic T-cell-mediated immune response against MART-1-expressing melanoma cells. The synthetic MART-1:27-35 HLA-A2-restricted peptide has an amino acid substitution, leucine to alanine at position 27, to increase its immunogenicity.
Irradiated allogeneic, HLA-A*0201 positive, plasmacytoid dendritic cells (pDCs) loaded with 4 melanoma peptides derived from the tumor associated antigens (TAAs) MelA/MART-1, gp100/pmel17, tyrosinase, and MAGE-A3, with potential immunostimulating and antineoplastic activities. Upon subcutaneous administration, the irradiated allogeneic pDCs may trigger functional multi-specific T cells from peripheral blood mononuclear cells and tumor-infiltrating lymphocytes, and activate the immune system to mount a cytotoxic T-lymphocyte response against HLA-A*0201 positive melanoma cancer cells expressing the TAAs MelA/MART-1, gp100/pmel17, tyrosinase, and MAGE-A3. These TAAs are upregulated in a variety of tumor cells. The pDCs are derived from a distinct subset of dendritic cells (DCs) with a plasma cell-like morphology and express a characteristic set of surface markers and may increase the anti-tumor immune responses.
A radioconjugate of biotin conjugated with the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA) and labeled with the beta-emitting isotope lutetium Lu 177 (Lu-177) that can be used for radioimmunotherapeutic purposes. Lutetium Lu 177 DOTA-biotin could be used in pre-targeting radioimmunotherapy, which pretreats the lesion with oxidized avidin that binds to protein amino groups on cells. As avidin binds to biotin, the radioisotope can be selectively delivered to cancer cells leading to tumor cell eradication.
A liposome-encapsulated formulation of the mesylate salt form of eribulin, a synthetic, macrocyclic ketone analogue of halichondrin B, a substance derived from the marine sponge genus Halichondria, with potential antineoplastic activity. Eribulin binds to the vinca domain of tubulin and inhibits both the polymerization of tubulin and the assembly of microtubules. This results in the inhibition of mitotic spindle assembly, the induction of cell cycle arrest at G2/M phase, as well as tumor cell apoptosis. Compared to the administration of eribulin alone, liposomal delivery of eribulin allows for a longer half-life, which allows increased drug concentration in target tissues while decreasing systemic toxicity.
A response indicating that an individual feels limited a lot.
A response indicating that an individual feels limited a little.
Autologous CD34+ hematopoietic stem cells transduced with Lenti-D lentiviral vector encoding the human ATP-binding cassette, sub-family D, member 1 (ABCD1) cDNA, for the potential treatment of childhood cerebral adrenoleukodystrophy (CCALD). Upon administration of the lenti-D/ABCD1-transduced autologous hematopoietic stem cells, the cells proliferate, and some travel to the brain and differentiate into microglial cells. The expressed ABCD1 restores the function of ALD protein (ALDP) and aids in the treatment of CCALD. In CCALD, the ABCD1 gene is mutated, leading to the inability of patients to metabolize very long chain fatty acids in cells of the brain.
Birth at 41 weeks and 0 days through 41 weeks and 6 days.
Birth when a fetus is between 34 weeks and 0 days through 36 weeks and 6 days gestational age.
Death of a fetus at 16 weeks, 0 days to 19 weeks, 6 days of gestation.
A A nutritional supplement containing the probiotic Lactobacillus strains, L. rhamnosus, L. jensenii, L. crispatus and L. gasseri, with protective and immunomodulating activities. The bacteria in this probiotic supplement colonize the vaginal tract and help to maintain as well as restore the composition of the normal, healthy vaginal flora. The four Lactobacillus species form a protective barrier that helps both to maintain the integrity of the vaginal tract and prevent the attachment of pathogenic bacteria and other harmful substances, thereby protecting against genitourinary infections.
A change in the amino acid residue at position 61 in the GTPase KRas protein where glutamine has been replaced by another amino acid.
A change in the amino acid residue at position 146 in the GTPase KRas protein where alanine has been replaced by another amino acid.
A variation in the amino acid sequence for the tyrosine-protein kinase JAK2 protein.
A change in the amino acid residue at position 931 in the tyrosine-protein kinase JAK2 protein where tyrosine has been replaced by cysteine.
A change in the amino acid residue at position 617 in the tyrosine-protein kinase JAK2 protein where valine has been replaced by phenylalanine.
A change in the amino acid residue at position 938 in the tyrosine-protein kinase JAK2 protein where arginine has been replaced by leucine.
A change in the amino acid residue at position 929 in the tyrosine-protein kinase JAK2 protein where methionine has been replaced by isoleucine.
A change in the amino acid residue at position 960 in the tyrosine-protein kinase JAK2 protein where isoleucine has been replaced by valine.
A change in the amino acid residue at position 935 in the tyrosine-protein kinase JAK2 protein where glycine has been replaced by arginine.
A change in the amino acid residue at position 985 in the tyrosine-protein kinase JAK2 protein where glutamic acid has been replaced by lysine.
A nucleotide substitution at position 2792 of the coding sequence of the JAK2 gene where adenine has been mutated to guanine.
A nucleotide substitution at position 1849 of the coding sequence of the JAK2 gene where guanine has been mutated to thymine.
An individualized, poly-neo-epitopic encoding, ribonucleic acid (RNA)-based cancer vaccine that targets a variety of patient-specific, immunogenic mutant epitopes, with potential immunostimulatory and antineoplastic activities. Upon intranodal administration, the RNA in the individualized mutanome vaccine is translated by antigen presenting cells (APCs) and the expressed protein is presented via major histocompatibility complex (MHC) molecules on the surface of the APCs. This leads to an induction of both cytotoxic T-lymphocyte (CTL) and memory T-cell immune responses against the patient-specific neoantigens.
The presence of single tumor cells or tiny clusters of tumor cells in a pathologic specimen.
A chromosomal rearrangement where a genetic segment of chromosome 3 has been inverted.
Fetal death greater than or equal to 20 weeks of gestation during labor with Apgar scores of 0 at 1 minute, 5 minutes and beyond.
Severe loss of blood pressure leading to inadequate tissue perfusion after the onset of labor but prior to the delivery of the fetus.
Elevated body temperature greater than or equal to 38C (100.4F) after the onset of labor but prior to the delivery of the fetus.
Infiltration of malignant glandular epithelial cells into the lamina propria of the intestine of the mouse without involvement of the submucosa.
An electrocardiographic finding of a premature ventricular complex which occurs between two normal QRS complexes which have normal timing. (CDISC)
Preterm birth from 20 weeks to 36 weeks, and 6 days of gestation that is necessitated by the medical condition of the mother or fetus.
The largest tumor lesion targeted by therapy.
The wrong booklet was provided to an individual.
A change in the nucleotide sequence of the variable region of the immunoglobulin heavy chain locus.
An immediate-release (IR) tablet formulation containing afuresertib, an inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Upon oral administration of the IR formulation, afuresertib binds to and inhibits the activity of Akt, which may result in the inhibition of PI3K/Akt signaling pathway, decreased tumor cell proliferation and the induction of tumor cell apoptosis in Akt-expressing tumor cells. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
An immediate-release (IR) formulation of onapristone, an orally bioavailable progesterone receptor (PR) antagonist, with antineoplastic activity. Onapristone binds to the PR and inhibits both PR activation and the associated expression of PR-responsive genes. This may inhibit PR-mediated proliferative effects in cancer cells overexpressing PR. PR is expressed on certain cancer cell types and plays a key role in proliferation and survival.
Modified T-lymphocytes expressing a 3rd generation chimeric antigen receptor (CAR) specific for the disialoganglioside GD2, which contains the CD3zeta chain, the signaling domains of the co-stimulatory molecules CD28 and CD134 (OX-40) and the suicide gene inducible caspase 9 (iCasp9), with potential immunomodulating and antineoplastic activities. Upon administration, iC9-GD2-CD28-OX40-expressing T lymphocytes target the GD2 antigen on tumor cells, thereby providing selective toxicity towards GD2-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered, which binds to the drug binding FKBP12-F36V domain and activates caspase 9, resulting in the apoptosis of the administered T-cells. The tumor associated antigen GD2 is overexpressed on the surface of almost all tumors of neuroectodermal origin. OX40 and CD28, both T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation.
A radiologic finding describing a region in an image with a signal lower than that of the surrounding regions.
A radiologic finding describing thin lines in an image with a signal higher than that of the surrounding tissue.
A radiologic finding describing a region in an image with a signal higher than that of the surrounding regions.
Abnormally high levels of aldosterone in the blood.
An area where large amounts of the radiotracer have accumulated and where there is a high level of chemical or metabolic activity.
Causes of death attributable to homicide or resulting from legal police intervention.
A topical formulation that can be used to relieve radiation dermatitis.
Inflammation of the fetal sac membranes that is characterized by neutrophilic infiltration of the amnion and chorion.
A dendritic cell (DC)-based cancer vaccine composed of autologous, type-1 polarized dendritic cells (DCs) pulsed with human leukocyte antigen (HLA)-A2-restricted HER-2-derived peptides, with potential immunomodulatory and antineoplastic activities. Autologous DCs were treated with GM-CSF, interleukin-4, interferon-gamma and bacterial lipopolysaccharide (LPS), a toll-like receptor type 4 agonist, to produce highly polarized DCs (alphaDC1) that are capable of producing high levels of interleukin-12p70 (IL-12p70). Upon administration, HER2-pulsed autologous DC vaccine may stimulate a potent cytotoxic T-lymphocyte (CTL) response against HER-2-positive tumor cells, which may result in tumor cell death and decreased tumor growth. HER-2, a tyrosine kinase receptor for epidermal growth factor (EGF) (also known as neu and ErbB2), is overexpressed by a variety of cancers.
A nanopolymer-based mouthwash formulation containing a mimetic of the glycosaminoglycan (GAG) heparan sulfate, with potential anti-mucositic and protective activities. Upon rinsing with the mouthwash, GAGs bind to heparan sulfate binding sites on macromolecules within the extracellular matrix (EMC), which prevents the destruction of the ECM and protects both growth factors and cytokines from being degraded. By replacing the GAGs damaged by chemotherapy and/or radiation, this mouthwash may protect healthy tissue against the cytotoxic effects of chemotherapy and radiation and may prevent against radio-chemotherapy-induced mucositis.
Transient blanching of the lower half of the body while in the lateral recumbent position, most commonly seen in premature or low birth weight infants.
A cell lysate derived from a lung cancer cell line, H1299, with potential immunostimulatory and antineoplastic activities. Upon intramuscular administration, the H1299 tumor cell lysate exposes the immune system to an undefined amount of tumor associated antigens (TAA), particularly cancer testis antigens (CTAs), which may result in the induction of both anti-tumoral cytotoxic T-lymphocytes (CTL) and antibody-dependent responses against TAA-expressing cells, leading to tumor cell lysis. CTAs, such as MAGE, are selectively expressed in a variety of cancers but are not expressed in normal, healthy cells outside the testis.
Carbohydrate intolerance first diagnosed during pregnancy. Diagnosis from abnormal oral glucose tolerance test (OGTT) and abnormal fasting or post-prandial glucose levels. Euglycemia achieved with medication.
Carbohydrate intolerance first diagnosed during pregnancy. Diagnosis from abnormal oral glucose tolerance test (OGTT) but normal glucose levels when fasting and two hours post-prandial. Euglycemia achieved with diet and/or exercise.
A cancer vaccine comprised of human leukocyte antigen (HLA)-A2-restricted folate binding protein (FBP) epitope J65 (9 amino acids; EIWTFSTKV), with potential immunostimulatory and antineoplastic activities. Upon intradermal injection, FBP J65 peptide vaccine may induce a specific cytotoxic T-lymphocyte (CTL) response against J65 FBP-expressing tumor cell types. FBP is a membrane-bound, tumor-associated antigen overexpressed in various tumor types, including breast, ovarian and endometrial cancers. J65 is a strongly immunogenic peptide.
The tosylate salt form of PLX7486, a selective inhibitor of the receptor tyrosine kinases colony-stimulating factor-1 receptor (CSF1R; fms) and neurotrophic tyrosine kinase receptor types 1, 2 and 3 (TrkA, TrkB, and TrkC, respectively) with potential antineoplastic activity. Upon administration, PLX7486 binds to and inhibits the activity of these tyrosine kinases. This inhibits Fms and Trk-mediated signaling transduction pathways that are upregulated in certain cancer cell types. This may eventually halt tumor cell proliferation in Fms and TrkA, TrkB, and/or TrkC-overexpressing tumor cells. Fms and TrkA, TrkB, and TrkC are receptor tyrosine kinases that are upregulated or mutated in a variety of tumors and promote tumor cell proliferation and survival.
An endoscopic finding indicating the presence of a wide-opened papilla filled with mucin.
A variation in the amino acid sequence for the fibroblast growth factor receptor 2 protein.
A change in the amino acid residue at position 372 in the fibroblast growth factor receptor 2 protein where serine has been replaced by cysteine.
A change in the amino acid residue at position 252 in the fibroblast growth factor receptor 2 protein where serine has been replaced by tryptophan.
A change in the amino acid residue at position 253 in the fibroblast growth factor receptor 2 protein where proline has been replaced by arginine.
A change in the amino acid residue at position 549 in the fibroblast growth factor receptor 2 protein where asparagine has been replaced by lysine.
A change in the amino acid residue at position 549 in the fibroblast growth factor receptor 2 protein where asparagine has been replaced by histidine.
A change in the amino acid residue at position 659 in the fibroblast growth factor receptor 2 protein where lysine has been replaced by glutamic acid.
A change in the amino acid residue at position 382 in the fibroblast growth factor receptor 2 protein where cysteine has been replaced by arginine.
A nucleotide substitution at position 758 of the coding sequence of the FGFR2 gene where cytosine has been mutated to guanine.
A nucleotide substitution at position 755 of the coding sequence of the FGFR2 gene where cytosine has been mutated to guanine.
A nucleotide substitution at position 1975 of the coding sequence of the FGFR2 gene where adenine has been mutated to guanine.
A nucleotide substitution at position 1647 of the coding sequence of the FGFR2 gene where thymine has been mutated to guanine.
A nucleotide substitution at position 1647 of the coding sequence of the FGFR2 gene where thymine has been mutated to adenine.
A nucleotide substitution at position 1645 of the coding sequence of the FGFR2 gene where cytosine has been mutated to guanine.
A nucleotide substitution at position 1144 of the coding sequence of the FGFR2 gene where thymine has been mutated to cytosine.
A nucleotide substitution at position 1124 of the coding sequence of the FGFR2 gene where adenine has been mutated to guanine.
A nucleotide substitution at position 1115 of the coding sequence of the FGFR2 gene where cytosine has been mutated to guanine.
A change in the nucleotide sequence of the FGFR2 gene.
An abnormality in the fetal heart rhythm associated with an increase in fetal heart rate above 160 beats per minute.
Abnormally low arterial blood oxygen concentration in a fetus.
A nasal spray containing a phosphate-buffered solution of the citrate salt form of fentanyl, a short-acting, synthetic, lipophilic anilidopiperidine opioid, with analgesic activity. Upon applying one puff in the nostril, the fentanyl is rapidly absorbed through the nasal mucosa and selectively binds to and activates mu-opioid receptors in the central nervous system (CNS), mimicking the effects of endogenous opiates. Due to its quick onset and short duration of action, the administration of fentanyl nasal spray may relieve breakthrough pain in adults already receiving maintenance opioid therapy for chronic pain.
A microscopic finding indicating the presence or absence of extravascular matrix loops in uveal melanoma.
Spread of uveal melanoma beyond the sclera.
An electrocardiographic finding of pathologic Q waves in leads V1 to V6, I and aVL, which is suggestive of myocardial infarction involving the anterior and anterolateral walls of the left ventricle. (CDISC)
An extended-release (ER) formulation of onapristone, an orally bioavailable progesterone receptor (PR) antagonist, with antineoplastic activity. Onapristone binds to the PR and inhibits both PR activation and the associated expression of PR-responsive genes. This may inhibit PR-mediated proliferative effects in cancer cells overexpressing PR. PR is expressed on certain cancer cell types and plays a key role in proliferation and survival.
An extended release (ER) oral tablet that contains flucytosine (5-FC), a fluorinated cytosine analog, with antifungal activity and potential anti-cancer activity. Following oral administration of ER 5-FC, the 5-FC is deaminated to its active metabolite 5-fluorouracil (5-FU). 5-FU replaces uracil during RNA synthesis, which consequently inhibits downstream protein synthesis. In addition, 5-FU is metabolized further to 5-fluorodeoxyuridylic acid monophosphate, which inhibits thymidylate synthetase. Inhibition of this enzyme interrupts nucleotide synthesis, DNA replication and cell proliferation. Negative regulation of protein synthesis, DNA replication and cell proliferation can lead to cell death. Following ingestion of ER 5-FC, intravenous injection of a retroviral vector encoding cytosine deaminase (TC 511) at a tumor site may result in higher local concentrations of 5-FU and its metabolites, and increased tumor cell death than other 5-FU treatment regimens.
A finding referring to a medical device that has been removed from the body, usually during a surgical procedure.
An antiquated term referring to a malignant lymphoma that is diffused and composed of small and large lymphocytes.
A malignant neoplasm of large lymphocytes, which resemble histiocytes.
A benign neoplasm composed of mesenchymal stromal cells.
A benign embryonal neoplasm of the kidney.
Bruising that is disproportionately high to the amount of trauma received or reported.
Fetal heart rate patterns not associated with maternal uterine contractions.
A well-defined area of unequivocally increased signal intensity on MRI or CT scan images compared with the normal-appearing surrounding tissues, following intravenous injection of an enhancing agent.
Irreparable damage to multiple organs/systems which is the result of chronic complications of diabetes. The affected organs/systems include the cardiovascular system, kidneys, eyes, nervous system, joints and feet.
Pregnancy loss at 6 weeks, 0 days to 9 weeks, 6 days of gestation of an embryo with crown-rump length less than 10 mm and no cardiac activity visible on ultrasonogram.
A change in the amino acid residue at position 719 in the epidermal growth factor receptor protein where glycine has been replaced by another amino acid.
Autologous human T-lymphocytes transduced with a retroviral vector encoding an anti-epidermal growth factor receptor (EGFR) chimeric T cell receptor (chimeric antigen receptor or CAR) gene coupled to the signaling domains from both CD3 zeta and CD137 (4-1BB), with potential immunostimulatory and antineoplastic activities. Upon administration, the chimeric EGFR antigen receptor-modified autologous T lymphocytes bind to the EGFR antigen on tumor cell surfaces; subsequently, EGFR-expressing tumor cells may be lysed. Following binding to EGFR, the 4-1BB co-stimulatory molecule signaling domain enhances both activation and signaling. Inclusion of the 4-1BB signaling domain may also increase the antitumor activity when compared to the inclusion of the CD3-zeta chain alone. EGFR, a receptor tyrosine kinase (RTK) overexpressed by a variety of cancer cell types, plays key roles in tumor cell proliferation and tumor angiogenesis.
A preparation of autologous, CD34-positive stem/progenitor cells transduced with a lentrivral vector encoding the human adenosine deaminase (ADA) gene under the control of the human elongation factor alpha short promoter (EFS), with potential to restore ADA expression and function. Autologous hematopoietic CD34+ cells are isolated from the patient's own bone marrow, peripheral blood or cord blood, and transduced with the EFS-ADA lentiviral vector ex vivo. Upon re-infusion of the EFS-ADA vector-transduced lymphocytes back into the patient, these cells may both restore ADA activity and prevent severe combined immunodeficiency (SCID) due to ADA deficiency. ADA, an enzyme that catalyzes the deamination of adenosine to inosine, plays a key role in the development and functioning of the immune system.
A finding pertaining to the quality of an ECG recording.
Birth at 37 weeks and 0 days through 38 weeks and 6 days.
Pregnancy loss before 10th week of gestation with documentation of a confirmed pregnancy.
Death of a fetus at 10 weeks, 0 days to 15 weeks, 6 days of gestation.
Duration from rupture of membranes to birth (in hours and minutes). (reVITALize)
A morphologic finding indicating reduction in the numbers of interlobular and septal bile ducts in the liver tissue.
A morphologic finding indicating the presence of typical or atypical proliferation of biliary epithelial cells in the portal tracts of the liver.
A reaction to a drug characterized by skin findings common to lupus including photosensitivity and butterfly rash; typically it resolves after drug discontinuation.
Donor-derived regulatory T-cells (Tregs), with potential immunomodulating activity. Tregs are a subset of CD4+ T cells that express high levels of CD25 (interleukin 2 receptor) and the transcription factor Foxp3. The donor CD4+CD25+ Tregs modulate immune responses and may induce tolerance to allogeneic organ transplants, such as hematopoietic stem cell transplants (HSCTs), thereby preventing graft-versus-host disease (GVHD).
A preparation of autologous, dominant-negative receptor (DNR)-expressing nasopharyngeal carcinoma (NPC)-specific cytotoxic T-lymphocytes (CTLs), with potential antineoplastic activity. The DNR-expressing NPC-specific CTLs specifically target Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1), latent membrane proteins (LMP) and BamHIA rightward frame 1 (BARF1), and are transduced with a retroviral vector expressing DNR, a dominant-negative form of the transforming growth factor beta (TGFb) receptor, which blocks TGF-beta-mediated signaling. Upon administration, the CTLs recognize and target NPC cells, which may result in both CTL-mediated cell lysis and the inhibition of tumor cell proliferation. Tumor-expressed TGF-beta inhibits T-lymphocyte activation and expansion; resistance to TGF-beta allows for optimal CTL activity. EBV infection plays a key role in NPC tumorigenesis.
A cell based cancer vaccine composed of mature polarized dendritic cells (alphaDC1) pulsed with six human leukocyte antigen (HLA)-A2-presented tumor blood vessel antigen (TBVA)-derived peptides, with potential immunostimulatory and antineoplastic activities. Dendritic cells (DCs) were treated with a ""type-1 polarizing cytokine cocktail"", including interleukin-1beta, tumor necrosis factor alpha (TNF-a), interferon-alpha (IFN-a), IFN-gamma and polyinosinic:polycytidylic acid (pI:C) to produce mature alpha type-1 polarized DCs (alphaDC1) that are capable of producing high levels of interleukin-12p70 (IL-12p70). The alphaDC1 are subsequently pulsed with TBVA-derived peptides, including delta-like homologue 1 (DLK1) 310-318, EPH receptor A2 (EPHA2) 883-891, beta-globin (HBB) 31-39, neuropilin-1 (NRP1) 433-441, regulator of G-protein signaling 5 (RGS5) 5-13 and tumor endothelial marker 1 (TEM1) 691-700. Upon administration, these DCs are able to induce a potent cytotoxic T-lymphocyte (CTL) response against the TBVAs expressed on tumor-associated stromal cells, which results in stromal cell lysis and inhibition of angiogenesis. Disrupting the surrounding tumor vasculature inhibits tumor cell growth and survival. alphaDC1 are able to induce a potent tumor antigen-specific CTL response due to their high co-stimulatory activity and the secretion of anti-cancer cytokines, such as IL-12p70.
A rare systemic and life-threatening infection associated with vaccination with the live attenuated strain of the Varicella-zoster virus, Oka.
Failure to contain thebacillus Calmette-Guerin (BCG) following vaccination leading to spread of BCG to many sites in the body. The tuberculosis vaccine BCG contains live attenuated Mycobacterium bovis. []
An adverse event, and/or its immediate sequelae which is associated with physical or mental disabilities that affect or limit the ability of a person to perform activities of daily living (eating, ambulation, toileting, etc.).
Congenital anomalies or fetal/neonatal complications in an infant that are linked to diabetes in the mother. In infants of women with established insulin-dependent diabetes mellitus, the risk of congenital malformations is 10 times higher than that in the general population, and the rate of stillbirths is five times higher than that in the general population. Macrosomia is also a common problem among infants of women with established insulin-dependent diabetes mellitus. Excess mortality among infants of women with preexisting insulin-dependent diabetes mellitus is predominantly due to congenital malformations.
Movement of a medical device to an unintended location within the body with resulting obstruction of an organ or vessel.
A finding referring to a medical device that has been demolished.
Nausea and vomiting occurring more than 24 hours following chemotherapy.
A radioconjugate labeled with the positron-emitting radioisotope, copper Cu 64, and also composed of plerixafor, a bicyclam and hematopoietic stem cell-mobilizing agent that targets the chemokine receptor CXCR4, with tumor imaging potential using positron emission tomography (PET)/computed tomography (CT). Upon administration, the plerixafor moiety blocks the binding of stromal cell-derived factor-1alpha (SDF-1alpha or CXCL12) to the cellular receptor CXCR4. In turn, the CXCR4-expressing tumor cells can be visualized using PET/CT and the resulting images could be used to predict a tumor's response to certain treatments. The expression of CXCR4 on cancer cells has been correlated with increased tumor cell survival, tumor progression, and increased metastatic potential.
A malformation in the hand or foot that is present at birth. Representative examples include syndactyly, polydactyly, brachydactyly, and thumb hypoplasia.
A morphologic finding indicating the presence of fibrosis around an intrahepatic bile duct in the liver tissue.
A formulation containing concentrated beetroot crystals, with potential antioxidant and protective activities. Concentrated beetroot crystals contain antioxidants, including betacyanin, which scavenge free radicals, and high levels of nitrates and folic acid. Intake of concentrated beetroot crystals leads to the conversion of nitrate to nitric oxide (NO). This may have a beneficial effect on blood flow and blood pressure through the stimulation of NO-mediated vasodilation. Additionally, this agent may decrease fatigue and increase physical performance.
A preparation of autologous T-lymphocytes that have been electroporated with an mRNA encoding a chimeric antigen receptor (CAR) consisting of an anti-human hepatocyte growth factor receptor (HGFR or cMet) scFv (single chain variable fragment) and the zeta chain of the TCR/CD3 complex (CD3-zeta) coupled to the co-stimulatory molecule 4-1BB (CD137), with potential antineoplastic activities. Upon intratumoral administration, cMet CAR-mRNA electroporated autologous T lymphocytes direct T-cells to cMet-expressing tumor cells, which induces a selective toxicity in cMet-expressing tumor cells and causes tumor cell lysis. The 4-1BB co-stimulatory molecule signaling domain enhances activation and signaling after recognition of cMet. The inclusion of the 4-1BB signaling domain may increase the antitumor activity as compared to the inclusion of the CD3-zeta chain alone. The mRNA CAR is expressed for a limited amount of time, which can prevent serious, unforeseen side effects. cMet, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis.
Inflammation of the fetal sac membranes, characterized by otherwise unexplained fever (at or above 38 degree C (100.4F)) with one or more of the following: uterine tenderness and/or irritability, leukocytosis, fetal tachycardia, maternal tachycardia, or malodorous vaginal discharge.
Gene expression profiling that classifies uveal melanomas into a high-grade group.
Gene expression profiling that classifies uveal melanomas into a low-grade group.
Uveal melanoma with intermediate metastatic risk as defined by gene expression profiling.
Uveal melanoma with low metastatic risk as defined by gene expression profiling.
Chronic hypertension in association with preeclampsia.
Nausea and/or vomiting co-occurring with a cycle of chemotherapy.
Overproduction of thyroid hormones due to a disorder originating within the hypothalamic-pituitary axis.
An orally bioavailable citrate salt form of TG02, a multi-kinase inhibitor for cyclin dependent kinase (CDK) subtypes 1, 2, 7 and 9, Janus-associated kinase 2 (JAK2), FMS-related tyrosine kinase 3 (FLT3, FLK2, STK1), with potential antineoplastic activity. Upon oral administration, CDK/JAK2/FLT3 Inhibitor TG02 binds to and inhibits the CDK subtypes, JAK2, and FLT3. TG02 also inhibits, to a lesser extent, TYK2, TYRO3, STAT5 and P38delta. This may result in both an induction of apoptosis and an inhibition of tumor cell proliferation in cancer cells that overexpress these kinases. JAK2, often upregulated or mutated in a variety of cancer cells, mediates STAT3 activation and plays a key role in tumor cell proliferation and survival. CDKs are serine/threonine kinases that play key roles in the regulation of the cell cycle and cellular proliferation. FLT3, a class III tyrosine kinase receptor, is overexpressed or mutated in most B lineage and acute myeloid leukemias.
Autologous T-lymphocytes transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD33 scFv (single chain variable fragment) coupled to the signaling domain of 4-1BB (CD137) and the zeta chain of the T-cell receptor (TCRzeta), with potential immunomodulating and antineoplastic activities. Upon transfusion, CD33-specific CAR retroviral vector-transduced autologous T lymphocytes target CD33-expressing tumor cells and induce selective toxicity in CD33-expressing tumor cells. Following binding to CD33, the 4-1BB co-stimulatory molecule signaling domain enhances both activation and signaling. Inclusion of the 4-1BB signaling domain may also increase the antitumor activity when compared to the inclusion of the CD3-zeta chain alone. CD33 is expressed on normal non-pluripotent hematopoietic stem cells as well as on myeloid leukemia cells.
Allogeneic T-lymphocytes transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment) coupled to the costimulatory signaling domain CD28, the signaling domain of 4-1BB (CD137), and the zeta chain of the T-cell receptor (TCR), with potential immunomodulating and antineoplastic activities. Upon transfusion, CD19CAR-CD28 zeta-4-1BB-expressing allogeneic T lymphocytes directs the T-lymphocytes to and induces selective toxicity in CD19-expressing tumor cells. CD28, a T-cell surface-associated co-stimulatory molecule, is required for T-cell activation, proliferation, and survival. The 4-1BB co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19. Furthermore, inclusion of the 4-1BB signaling domain may increase the antitumor activity compared to the inclusion of the CD28 costimulatory domain and TCR zeta chain alone. CD19 antigen is a B-cell specific cell surface antigen, which is expressed in all B-cell lineage malignancies.
T-lymphocytes transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) specific for syndecan-1 (CD138) (CART-138 T cells) coupled to the signaling domain of 4-1BB (CD137), and the zeta chain of the T-cell receptor (TCRzeta), with potential immunomodulating and antineoplastic activities. Upon transfusion, CD138CAR- CD137/TCRzeta -expressing T lymphocytes directs the T-lymphocytes to syndecan-1-expressing tumor cells and induces selective toxicity in those tumor cells. The 4-1BB co-stimulatory molecule signaling domain enhances activation and signaling after recognition of syndecan-1. Syndecan-1, a type 1 transmembrane proteoglycan and tumor associated antigen, is overexpressed in a variety of cancer cells. It plays a key role in the regulation of cell growth, differentiation, and adhesion, and its expression is correlated with poor prognosis.
A cell-based cancer vaccine comprised of autologous dendritic cells (DCs) pulsed with human leukocyte antigen (HLA)-A2-restricted peptides derived from the CD133 antigen, with potential antineoplastic activity. Upon intradermal administration, the CD133 antigen peptide-pulsed autologous DC vaccine may stimulate an anti-tumoral cytotoxic T-lymphocyte (CTL) response against CD133-expressing tumor cells, resulting in tumor cell lysis. CD133, a cancer stem cell marker, is expressed on hematopoietic stem and progenitor cells and overexpressed on many types of cancer cells; it is associated with resistance to chemotherapy and increased cancer survival. HLA-A2 is an MHC class I molecule that presents antigenic peptides to CD8+ T-cells. Epitope design that is restricted to those epitopes that bind most efficiently to HLA-A2 may improve antigenic peptide immunogenicity.
An eye drop solution containing the sodium salt form of carboxymethylcellulose (CMC) used as artificial tears. Upon application of the drops into the eye, carboxymethylcellulose sodium lubricates the eye and prevents or relieves dryness and irritation.
An orally bioavailable, tryptophan hydroxylase (TPH) inhibitor prodrug labeled with carbon C 14, which could be used to evaluate the pharmacokinetic profile of telotristat etiprate. Upon administration, telotristat etiprate is converted to its active moiety, telotristat (LP-778902), which binds to and blocks the activity of TPH. This may result in a reduction in peripheral serotonin (5-HT) production and improvement of serotonin-mediated gastrointestinal adverse side effects, such as severe diarrhea. TPH, the rate-limiting enzyme in serotonin biosynthesis, is overexpressed in carcinoid tumor cells. Telotristat radiolabeled with carbon C 14 facilitates the evaluation of the pharmacokinetic characteristics of this agent, including its absorption, distribution, metabolism, and excretion (ADME).
A radioconjugate containing the orally available selumetinib, an inhibitor of mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) types 1 and 2, labeled with the radioisotope carbon C 14. Upon oral administration, selumetinib selectively inhibits MEK1/2, which prevents the activation of MEK1/2 dependent effector proteins and transcription factors. This leads to an inhibition of cellular proliferation in MEK1/2-overexpressing tumor cells. MEK 1 and 2 are dual specificity kinases that are essential mediators in the activation of the RAS/RAF/MEK/ERK pathway and are often upregulated in various cancer cells. Selumetinib radiolabeled with carbon C-14 may be used as a radiotracer for pharmacokinetic studies of this agent, including its absorption, distribution, metabolism and excretion (ADME).
A radioconjugate composed of the platinum agent oxaliplatin labeled with the isotope carbon C 14, that can be used to predict the response to oxaliplatin therapy using accelerator mass spectrometry (AMS). Upon intravenous administration of a microdose of carbon C 14 oxaliplatin, the oxaliplatin moiety covalently links to DNA and forms mono- and di-DNA adducts. The platinum-DNA adduct formation can be measured through quantification of C14-labeled drug-DNA adducts by using AMS. By measuring the microdose-induced DNA damage, the response to oxaliplatin-based chemotherapy can be assessed and predicted. Measurements that indicate either low drug-DNA adduct formation or increased DNA repair (C14 removal from DNA) are correlated with increased resistance to platinum-based chemotherapeutics.
A radioconjugate composed of temozolomide, a imidazotetrazine analog of dacarbazine, labeled with the radioisotope carbon C11, with potential positron emission tomography (PET) imaging activity. As a cytotoxic alkylating agent, temozolomide is hydrolyzed at physiologic pH to the pharmacologically active compound, 5-(3-methyl-(triazen-1-yl)-imidazole)-4-carboxamide (MTIC). MTIC is further hydrolyzed to 5-aminoimidazole-4-carboxamide (AIC) and a methyldiazonium cation. The cation is able to methylate DNA, particularly at the O6 and N7 positions of guanine residues, resulting in cell cycle arrest, inhibition of DNA replication and the induction of apoptosis. Temozolomide is metabolized to MITC at all sites, crosses the blood-brain-barrier and penetrates well into the central nervous system. Upon PET, the biodistribution, uptake in cancer cells and the efficacy of temozolomide can be assessed.
A combination preparation containing camphor and menthol with anti-pruritic activity. Camphor, a terpenoid extracted from camphor laurel (Cinnamonum camphora) tree, can be absorbed readily through the skin and produces a cooling feeling similar to that of menthol. This formulation is used to relieve itching and cools irritated skin due to sunburn, dry and itchy skin, poison ivy, poison oak, insect bites, minor cuts, burns and abrasions.
An electrocardiographic finding of complete or incomplete right bundle branch block accompanied by ST elevation in leads V1-V3. This may be noted at rest or can be provoked by medication challenge. (CDISC)
A response indicating that an individual is or was bothered just a little.
The return of a booklet is or was not requested.
An orally available, probiotic supplement containing the non-pathogenic microorganisms Lactobacillus acidophilus, L. plantarum, L. salivarius and Bifidobacterium lactis, with potential anti-inflammatory, immunomodulating and protective activities. Upon oral ingestion, the naturally-occurring bacterial components in this dietary supplement may improve digestion and help maintain adequate colonization of the gastrointestinal (GI) tract by modulating the composition of the normal microflora. During colonization in the GI tract, the bacteria may form a protective intestinal barrier that may prevent both damage to the mucosal epithelia caused by toxins and attachment of potential pathogens, which protects against bacterial translocation and infections. In addition, this agent may both reduce the secretion of pro-inflammatory cytokines, including interleukin-10, and potentiate natural and acquired immunity.
A molecular genetic abnormality in the kinase domain of the BCR-ABL fusion gene that results in resistance to tyrosine kinase inhibitors.
Abnormally low level of basophils in the blood.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysates from sarcoma cells with potential immunostimulatory and antineoplastic activities. Upon administration, the autologous sarcoma lysate-pulsed dendritic cell vaccine exposes the immune system to an undefined amount of sarcoma-type tumor associated antigens (TAA), which may result in the induction of both specific anti-tumoral cytotoxic T lymphocytes (CTL) and antibody-dependent responses against the sarcoma TAA-expressing cells, resulting in sarcoma cell lysis.
Peripheral blood T-lymphocytes (PBTLs) transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment) coupled to the costimulatory signaling domain CD28, the signaling domain of 4-1BB (CD137), and the zeta chain of the T-cell receptor (TCR), with potential immunomodulating and antineoplastic activities. Upon transfusion, PBTL CD19CAR-28/CD137zeta directs the T-lymphocytes to CD19-expressing tumor cells and induces selective toxicity in CD19-expressing tumor cells. CD28, a T-cell surface-associated co-stimulatory molecule, is required for full T-cell activation, proliferation, and survival. The 4-1BB co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19. Furthermore, inclusion of the 4-1BB signaling domain may increase the antitumor activity compared to the inclusion of the CD28 costimulatory domain and TCR zeta chain alone. CD19 antigen is a B-cell specific cell surface antigen, which is expressed in all B-cell lineage malignancies.
Human autologous mesenchymal stem cells (MSCs) harvested from the bone marrow of a patient and genetically modified with a self-inactivating retroviral vector expressing the suicide gene herpes simplex virus thymidine kinase (HSV-TK), that can be used to activate synthetic acyclic guanosine analogues when co-administered. Upon intravenous administration of autologous mesenchymal stem cells apceth_101, the cells are actively recruited to the tumor stroma, differentiate into more mature mesenchymal cells, and become part of the tumor microenvironment. When a synthetic acyclic guanosine analogue, such as ganciclovir, is co-administered, the HSV-TK within the HSV-TK-transduced MSCs will monophosphorylate this prodrug. Subsequently the monophosphate form is further converted to the diphosphate form and then to its active triphosphate form by cellular kinases. The active form of ganciclovir kills the HSV-TK-transduced MSCs and leads to a bystander effect, which eliminates neighboring cancer cells. Therefore, synthetic acyclic guanosine analogues are activated only at the tumor site, which increases their local efficacy and reduces systemic toxicity.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with both a lysate from autologous melanoma cells containing tumor associated antigens (TAAs) and a synthetic peptide derived from the tumor associated antigen human cancer-testis antigen NY-ESO-1, with potential immunostimulatory and antineoplastic activities. Upon administration, autologous melanoma lysate/NY-ESO-1-pulsed autologous DC vaccine may stimulate the immune system to mount anti-tumoral cytotoxic T lymphocyte (CTL) and antibody-mediated immune responses against melanoma cells, which may result in melanoma cell lysis. NY-ESO-1 is expressed in normal testes and on the surfaces of various tumor cells, and plays a key role in tumor cell proliferation and survival.
Genetically modified, autologous varicella zoster virus (VZV)-specific T-lymphocytes transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) specific for the disialoganglioside GD2, which contains the signaling domains for the co-stimulatory molecules CD28 and CD134 (OX-40), and the suicide gene, inducible caspase 9 (iCasp9 or iC9), with potential immunomodulating and antineoplastic activities. Upon intravenous administration, iC9-GD2-CD28-OX40-expressing T lymphocytes target the GD2 antigen on tumor cells for selective toxicity against GD2-expressing tumor cells. iCasp9 consists of a full-length caspase 9, including its caspase recruitment domain, linked to a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V). If the administered T cells lead to unacceptable side effects, the chemical homodimerizer AP1903 can be administered, which binds to the FKBP12-F36V drug binding domain, activates caspase 9, and results in apoptosis of the administered T-cells. Expression of the iCasp9 gene in T cells for adoptive transfer increases safety and broadens the scope for their clinical applications. The tumor associated antigen GD2 is overexpressed on the surface of almost all tumors of neuroectodermal origin. OX40 and CD28, both T-cell surface-associated co-stimulatory molecules, are required for full T-cell activation. An additional VZV vaccine can be administered to increase T-cell activity.
A lethally irradiated, autologous colorectal cancer vaccine consisting of patient-specific colorectal cancer cells genetically modified to secrete the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), with potential immunostimulating and antineoplastic activities. Upon vaccination, the autologous GM-CSF-secreting lethally irradiated colorectal cancer cell vaccine releases GM-CSF. In turn, GM-CSF may increase the body's immune response against tumor cells by promoting the maturation and activation of dendritic cells (DCs), and enhancing tumor-specific antigen presentation to both B- and T-cells, which leads to better recognition of tumors by the immune system. In addition, GM-CSF promotes antibody-dependent cellular cytotoxicity (ADCC), and increases interleukin-2-mediated lymphokine-activated killer cell function.
A preparation of cytotoxic, autologous acute myelogenous leukemia (AML)-reactive T lymphocytes (CTL), with potential immunomodulating and antineoplastic activities. The autologous cultured AML-specific CTLs are prepared using a specific AML-CTL culture method. Autologous peripheral blood lymphocytes are taken from an AML patient and the autologous AML blasts are treated with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4), both of which promote ex vivo differentiation of AML blasts into dendritic cells (DCs). In the same culture, T cells are treated and activated by low-dose interleukin 2 (IL-2), and expanded using anti-CD3. This results in cultured AML-reactive CTLs which are administered back into the patient after autologous hematopoietic stem cell transplant (AHSCT). The autologous cultured AML-specific CTLs may eradicate residual AML cells.
Genetically modified autologous T-lymphocytes transduced with a replication incompetent retroviral vector expressing a chimeric T cell antigen receptor (CAR) consisting of an anti-CD19 scFv (single chain variable fragment), fused to the extracellular, transmembrane and intracellular signaling domains of the T cell co-stimulatory receptor CD28 and the cytoplasmic signaling domain of the zeta chain of the TCR/CD3 complex (CD3-zeta) (CAR19-28z), with potential antineoplastic activities. Upon intravenous administration, autologous CD19-28z CAR-expressing T-lymphocytes are directed to CD19-expressing tumor cells, which induces selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. The CD28 co-stimulatory molecule signaling domain enhances activation and signaling after recognition of CD19. The inclusion of the CD28 signaling domain may increase proliferation of T-cells and antitumor activity compared to the inclusion of the CD3-zeta chain alone.
An orally bioavailable agent that is selective towards adrenal cortex cells with potential antitumor activity. Upon administration, ATR-101 selectively kills adrenal and adrenal cancer cells, through an unknown mechanism.
A radiologic finding indicating the presence of new vessels on arterial phase imaging within or surrounding a lesion.
An arrhythmia that is detected on an electrocardiograph.
No specification on the details of the primary tumor growth.
A humanized, bivalent anti-von Willebrand factor (VWF) nanobody with potential anti-platelet activity. Anti-von Willebrand factor nanobody specifically binds to the A1 domain of the VWF molecule, thereby inhibiting and neutralizing VWF activity. This prevents the interaction of VWF with the platelet glycoprotein (Gp)Ib-IX-V receptor and prevents VWF-mediated platelet aggregation. VWF is a glycoprotein and plays a key role in blood coagulation. Increased VWF, which is seen in a number of diseases, is associated with an increased risk in thrombosis. The nanobody formulation allows for rapid distribution, onset of action and clearance. The nanobody is based on the smallest functional fragments of single-chain antibodies that naturally occur in the Camelidae family.
Autologous human CD8-positive T-lymphocytes transduced with a recombinant retroviral vector encoding a chimeric T cell receptor (chimeric antigen receptor or CAR) consisting of an anti-vascular endothelial growth factor receptor type 2 (VEGFR2) scFv (single chain variable fragment), linked to the transmembrane domain of human CD8alpha and coupled to the costimulatory signaling domains of both CD28 and 4-1BB (CD137), and the CD3 zeta chain of the T-cell receptor (TCR), with potential immunostimulating and antineoplastic activities. Autologous peripheral blood lymphocytes (PBLs) from a patient with VEGFR2-positive cancer are pulsed with a retroviral vector that encodes the CAR gene specific for VEGFR2. After expansion in culture and reintroduction into the patient, the anti-VEGFR2 CAR-gene engineered CD8+ lymphocytes express anti-VEGFR2-CAR on their cell surfaces and bind to the VEGFR2 antigen on tumor cell surfaces. Subsequently, VEGFR2-expressing tumor cells are lysed. VEGFR2, a receptor tyrosine kinase (RTK) overexpressed by a variety of cancer cell types, belongs to the VEGFR superfamily and plays key roles in tumor cell proliferation, survival, invasion and tumor angiogenesis. The co-stimulatory molecules are required for optimal T-cell activation.
An antibody-drug conjugate (ADC) comprised of a monoclonal antibody against human tissue factor (TF) covalently coupled, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antiangiogenic, anticoagulant and antineoplastic activities. Upon administration, anti-TF monoclonal antibody-MMAE conjugate binds to cell surface TF and is internalized. The antibody moiety prevents binding of TF to factor VIIa (FVIIa) and interferes with the activation of factor X (FX) into FXa. This may prevent thrombin formation and cancer-associated venous thromboembolism, and may inhibit angiogenesis and tumor cell proliferation. After internalization of the agent, the MMAE moiety is released by proteolytic cleavage. It then binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis. TF, a transmembrane protein and initiator of the coagulation cascade, is overexpressed in many tumor cells and tumor-resident endothelial cells. Expression of TF is correlated with metastasis, angiogenesis, tumor cell growth and tumor-associated thrombosis.
Human autologous CD62L-positive T-lymphocytes transduced with a retroviral vector encoding a T cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1, with potential antineoplastic activity. Following leukapheresis, isolation of lymphocytes, expansion ex vivo, transduction, and reintroduction into the patient, the anti-NY-ESO1 TCR-transduced autologous CD62L+-derived T-Lymphocytes bind to NY-ESO-1-overexpressing tumor cells. This may result in cytotoxic T-lymphocyte (CTL)-mediated elimination of NY-ESO-1-positive cancer cells. NY-ESO-1, a tumor associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types. CD62L, also called L-selectin, is a lymphoid homing receptor and differentiation marker and is expressed on a subset of CD8-positive T-lymphocytes; it is involved in the migration of T-lymphocytes to lymph nodes and may improve the efficacy for ex vivo-expanded T-cells following adoptive cell therapy.
Allogeneic human T-lymphocytes transduced with a retroviral vector encoding an anti-epidermal growth factor receptor (EGFR) variant III (EGFRvIII) mutant chimeric T cell receptor (chimeric antigen receptor or CAR) gene coupled to the signaling domains from CD8, CD28, 4-1BB (CD137) and CD3 zeta, with potential immunostimulatory and antineoplastic activities. Upon administration, the anti-EGFRvIII CAR-transduced allogeneic T lymphocytes bind to the EGFRvIII antigen on tumor cell surfaces; subsequently, EGFRvIII-expressing tumor cells may be lysed. EGFRvIII, an in-frame deletion of exons 2-7 in the EGFR gene, is overexpressed by a variety of cancer cell types and absent in normal, healthy cells; it plays a key role in tumor cell proliferation, tumor angiogenesis and radio- and chemoresistance.
Any monoclonal antibody directed against the cell surface glycoprotein CD8, regardless of the antibody type.
Any monoclonal antibody directed against the cell surface glycoprotein CD7, regardless of the antibody type.
Any monoclonal antibody directed against the cell surface glycoprotein CD5, regardless of the antibody type.
Any monoclonal antibody directed against the cell surface glycoprotein CD4, regardless of the antibody type.
Any monoclonal antibody directed against the cell surface glycoprotein CD3, regardless of the antibody type.
Any monoclonal antibody directed against the cell surface glycoprotein CD19.
Allogeneic T-lymphocytes derived from peripheral blood mononuclear cells (PBMC) transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) consisting of both the light and heavy chain variable regions of anti-CD19 monoclonal antibody FMC63, coupled to the molecule CD28 and the signaling domain of the zeta chain of the T-cell receptor (TCR) (FMC63-28Z), with potential immunomodulating and antineoplastic activities. Upon transfusion, the anti-CD19-CAR FMC63-28Z retroviral vector-transduced allogeneic T lymphocytes specifically recognize and kill CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen, which is expressed in all B-cell lineage malignancies and normal B-cells.
An acute symptomatic tearing of the uterine wall prior to the onset of labor.
Fetal death greater than or equal to 20 weeks of gestation prior to labor with Apgar scores of 0 at 1 minute, 5 minutes and beyond.
Presence of a blood clot in the maternal vascular system which originated from a distant site during the antepartum period.
Presence of bacterially-infected tissue in the maternal vascular system which originated from a distant site during the antepartum period.
Presence of a large air bubble in the maternal vascular system which originated from a distant site during the antepartum period.
Any monoclonal antibody directed against an alpha-beta T-Cell receptor.
A herbal-based mouthrinse containing aloe, anise, ascorbic acid, clove, peppermint, spearmint and thyme, with potential anti-mucositic activity. When aloe/anise/ascorbic acid/clove/peppermint/spearmint/thyme-based mouthwash is used as a rinse, the ingredients in this agent may prevent or decrease inflammation and bacterial infections.This may prevent or inhibit radiotherapy- or chemotherapy-induced mucositis and decreases the pain associated with mucositis.
An allogeneic melanoma cell vaccine derived from a cell line with high expression of melanoma associated antigens and genetically modified to express both HLA-A2 and 4-1BB ligand, with potential immunostimulating and antineoplastic activities. Upon administration, the 4-1BB ligand of the allogeneic HLA-A2/4-1BB ligand-expressing melanoma vaccine binds to 4-1BB on activated T-lymphocytes, which induces a strong immune response against HLA-A2 positive melanoma cells.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with lysates from an allogeneic glioblastoma (GBM) stem-like cell line, with potential immunostimulatory and antineoplastic activities. Upon administration allogeneic glioblastoma stem-like cell line lysate-pulsed autologous dendritic cell vaccine exposes the immune system to GBM stem cell antigens, which may result in cytotoxic T lymphocyte (CTL) and antibody responses against GBM cells. This leads to GBM cell lysis. GBM stem-like cells contain a specific range of antigens that are essential for the neoplastic growth and survival of GBM cells.
A response indicating that something happens or happened a little of the time.
Excessive secretion of the androgen hormones dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione, from the adrenal gland. Clinical manifestations may include virilization.
Abnormally low or absent secretion of the androgen precursor hormones dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione, from the adrenal gland.
A human serotype 5, replication-defective, first generation adenoviral vector, with the viral E1a and E3 protein encoding regions deleted, which is engineered to express the herpes simplex virus thymidine kinase (HSV-tk) gene under the transcriptional control of the CMV promoter. This agent, when administered in conjunction with a synthetic acyclic guanosine analogue, possesses potential antineoplastic activity. Upon administration into the peritumoral region after tumor resection, adenoviral vector encoding HSV thymidine kinase is transduced into tumor cells, and HSV-tk is expressed. Tumor cells expressing HSV-tk are sensitive to synthetic acyclic guanosine analogues. Subsequent administration of a synthetic acyclic guanosine analogue, such as valacyclovir (VCV) or ganciclovir (GCV), kills the tumor cells expressing HSV-tk. The release of tumor-associated antigens (TAA) by dying tumor cells may then stimulate an antitumor cytotoxic T lymphocyte (CTL) response, directed aganst any remaining tumor cells.
A human serotype 5, replication-defective, first generation adenoviral vector, with the viral E1a and E3 protein encoding regions deleted, which is engineered to express the soluble, immune-mediated stimulatory gene human fms-like tyrosine kinase 3 ligand (Flt3L), under the transcriptional control of the CMV promoter, with potential immunostimulating activity. Upon administration, Ad-hCMV-Flt3L is transduced into tumor cells and Flt3L is expressed. Flt3L stimulates both the proliferation of dendritic cells (DCs) and their migration to the tumor site. Upon exposure to the tumor-associated antigens (TAA) released from dying glioma cells, which were killed by thymidine kinase-mediated valacyclovir-induced tumor cell death, the DCs initiate a specific immune response against any remaining TAA-expressing tumor cells. Flt3L is a hematopoietic growth factor and ligand for the Flt3 tyrosine kinase receptor.
A replication-defective, recombinant adenoviral serotype 5 (Ad5) encoding human guanylyl cyclase C (hGCC) and the synthetic Pan DR epitope (PADRE), with potential antineoplastic and immunomodulating activities. Upon intramuscular administration, the Ad5-hGCC-PADRE vaccine expresses hGCC, which may induce both humoral and cellular immune responses against tumor cells expressing the hGCC antigen. This results in the immune-mediated inhibition of tumor cell proliferation, and leads to tumor death. The hGCC protein is normally restricted to intestinal epithelial cells but is overexpressed by metastatic colorectal tumors. PADRE is a helper T-lymphocyte epitope that is able to augment the magnitude and duration of the cytotoxic T-lymphocyte (CTL) response.
An electrocardiographic finding of pathologic Q waves with accompanying ST elevation in leads V1 to V6, I and aVL, which is suggestive of acute myocardial infarction involving the anterior and anterolateral walls of the left ventricle. (CDISC)
Causes of death attributable to accidents or their adverse events.
A clinical finding indicating the presence of a firm, indurated, or nodular lesion, which is suspicious for malignancy, during colorectal examination.
A clinical finding indicating the presence of a lesion, which is highly suspicious for malignancy, during colorectal examination.
Acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage, including monoblasts, promonocytes, and monocytes. Bleeding disorders are common presenting features.
Meckel-Gruber syndrome is a severe autosomal recessive ciliopathy classically defined by the triad of encephalocele, polydactyly, and renal and biliary ductal dysplasia. Clinical heterogeneity exists even within families (summary by Shaheen et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of Meckel syndrome, see MKS1 (249000).
Disordered behavior associated with clinically significant distress or impairment in social, occupational or other important areas of functioning and persistent difficulty parting with possessions due to a perceived need to save the items and distress associated with discarding them. (from DSM-V) The quantity of collected items sets the behavior apart from normal collecting behaviors.
A pharmaceutical preparation of the ANTI-HIV AGENTS elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate that is used in the treatment of HIV INFECTIONS.
In addition to classic type 1 (see 222100) and type 2 (see 125853) diabetes mellitus, atypical presentations are seen, particularly in populations of African ancestry. Ketosis-prone diabetes, the most common atypical form, is characterized by an acute initial presentation with severe hyperglycemia and ketosis, as seen in classic type 1 diabetes, but after initiation of insulin therapy, prolonged remission is often possible with cessation of insulin therapy and maintenance of appropriate metabolic control. Metabolic studies show a markedly blunted insulin secretory response to glucose, partially reversible with the improvement of blood glucose control. Variable levels of insulin resistance are observed, especially in obese patients. Pancreatic beta-cell autoimmunity is a rare finding, and association with type 1 susceptibility HLA alleles is variable (Sobngwi et al., 2002).
A classic form of congenital adrenal hyperplasia that is characterized by severe 21-hydroxylase deficiency, resulting in glucocorticoid and mineralocorticoid deficiency, but without clinically significant salt wasting, and with androgen excess, which causes virilization in female infants.
A rare inherited disorder due to the ectopic expression of the aldosterone synthase in the fascicular zone of the adrenal gland and marked with early severe hypertension (often occurring before the age of 20), biological signs of primary aldosteronism of variable intensity, and an abnormal elevated level of 18-oxo- and 18-hydroxycortisol.
A familial condition where too much aldosterone is produced by the adrenal glands which can lead to lowered levels of potassium in the blood.
A form of spastic cerebral palsy affecting all four limbs with neck and head paralysis, often accompanied by eating and breathing complications.
A form of spastic cerebral palsy affecting both sides of the body; the Surveillance of Cerebral Palsy in Europe (SCPE) does not recommend the use of diplegia/quadriplegia terms, and recommends using instead the term bilateral spastic cerebral palsy and subtypes.
Inflammation of the temporomandibular joint in the area located posterior to the articular disc.
A condition following an arterial switch operation to correct transposition of the great arteries, in which the old aortic root becomes the new pulmonary root and where the new pulmonary valve does not prevent backflow to the right ventricle.
A form of dyskinetic cerebral palsy with a combination of chorea and athetosis; movements are irregular, but twisting and curving.
Subarachnoid haemorrhage not due to rupture of aneurysm.
Bleeding into the area between the arachnoid membrane and the pia mater, limited to the subarachnoid spaces around the midbrain.
Ankle pain lasting less than three months.
Characterised by severe headaches, with or without other acute neurological symptoms and diffuse segmental constriction of cerebral arteries.
An invasive breast carcinoma characterized by the presence of clusters of malignant cells located within artifactual clear stromal spaces that resemble vascular spaces.
A measurement of the length of the span between the anus and the base of the genitalia.
The reactivation of latent hepatitis C infection usually caused by a medicinal agent, such as an immunosuppressant.
A phosphaturic mesenchymal tumor that has metastasized from its original site of growth to other anatomic sites.
A usually large and aggressive tumor with perivascular epithelioid cell differentiation characterized by the presence of marked nuclear atypia, pleomorphism, increased mitotic activity, necrosis, and infiltrative margins. The most common metastatic sites are liver, lungs, lymph nodes, and bone.
Morphological alterations to squamous cells that fall short of low-grade dyskaryosis but that cannot be identified with certainty as the consequence of inflammatory, reactive, metaplastic, or hormonal processes.
A rare benign chondroid and osteoid matrix-producing neoplasm of bone characterized by extensive myxoid changes. It may be a locally destructive neoplasm and has been reported in patients with Carney complex.
An ectopic tooth that has erupted on the lingual aspect of the maxilla or mandible.
A reactive fibrous lesion of adductor magnus and aponeurotic origin of the medial head of gastrocnemius of the distal femur.
A genetic cause of hypertension secondary to primary aldosteronism that is not suppressed with dexamethasone. Patients present with an adrenal adenoma that secretes aldosterone.
Acute neurological dysfunction caused by haemorrhage localised to the subcortex, basal ganglia, and the diencephalon.
This is a postprocedural valvular heart disease which results in the narrowing of the orifice of the tricuspid valve of the heart. It is a relatively rare condition that causes stenosis- increased resistance to blood flow through the valve.
A form of spastic cerebral palsy affecting three limbs; this could be both arms and a leg, or both legs and an arm. In some instances, it has referred to one upper and one lower extremity and the face.
Acquired angio-oedema due to the presence of neutralising antibodies against C1 inhibitor.
Condition where foot exhibits an arch when non-weight bearing but shows collapse of the arch in stance.
Arthralgia of knee less than three months.
Describes the time in a woman's life when menstrual periods become irregular as she approaches menopause. This is usually three to five years before menopause and is often marked by many of the symptoms of menopause, including hot flashes, mood swings, night sweats, vaginal dryness, trouble concentrating, and infertility.
This is a non-rheumatic heart valve disorder in which outflow of blood from the right ventricle of the heart is obstructed at the level of the pulmonic valve, with regurgitation.
Edema in the region of the upper eyelid.
A benign nerve sheath tumor characterized by the combination of histologic features seen in schwannomas, neurofibromas, and perineuriomas.
Occurs where a missing tooth or delayed replacement of lost teeth leads to extrusion of the opposing teeth into the edentulous space.
A form of dyskinetic cerebral palsy with irregular movements that are not repetitive or rhythmic, and tend to be more jerky and shaky.
Osteoporosis that results from medical conditions or treatments that interfere with the attainment of peak bone mass, contributing to the structural deterioration of bone tissue.
Bleeding into the area between the arachnoid membrane and the pia mater surrounding the brain. Only intrasulcal bleeding within the hemispheric convexities, it does not result from aneurysm or trauma.
Continuous involuntary contraction of the masticatory muscle.
Nonsyndromic premature fusion of multiple sutures.
An ulcerated nodule of cornea or conjunctiva.
A condition following an arterial switch operation to correct transposition of the great arteries, in which the old pulmonary root becomes the new aortic root and where the new aortic valve is narrowed.
Insufficient distance between the peri-implant mucosa margin and the bone crest.
CPPD crystals are demonstrated in tissues or synovial fluid by definite means (for example, chemical analysis) or by compensated polarised light microscopy and typical calcifications are seen on radiographs.
Forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio is less than lower limits of normal (LLN), but FEV1 is more than its LLN.
Class of chemicals that are analogs or derivatives of 1-phenylpropan-2-amine, including synthetic and naturally occurring amphetamines.
A person's ability to walk in corridor on unit.
A tumor with perivascular epithelioid cell differentiation characterized by the absence of pleomorphism and scarcity or absence of mitotic figures.
Crowded cells with pseudostratification but little nuclear abnormality, or coarsely clumped chromatin with entirely normal architecture.
A process characterized by an initial immune response to a foreign tissue antigen of the same species resulting in the production of specific immunologic memory cells, antibodies and immune effector cells which may lead to cellular destruction or transplant rejection.
Typically thunderclap headache recurring over 1-2 weeks, often triggered by sexual activity, exertion, Valsalva maneuvers and/or emotion. Headache can remain the sole symptom of reversible cerebral vasoconstriction syndrome.
Acute myeloid leukemia characterized by the presence of t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22). These cytogenetic abnormalities result in disruption of the transcription factor CBF, which is a regulator of normal hematopoiesis.
Awareness of an illusory extra limb in addition to the real regular limbs.
Immature red blood cells (erythroid cells) in the bone marrow are abnormal in size, shape, organisation, and/or number.
Near the time of trough substance concentration after administration of a substance.
A rare, autosomal dominant inherited syndrome caused by mutations in the DICER1 gene. People with this syndrome are at an increased risk of developing pleuropulmonary blastoma, cystic nephroma, Sertoli-Leydig cell tumor of the ovary, and multinodular goiter.
Sexual grooming is the deliberate befriending and establishing of an emotional connection with a victim in order to sexually abuse.
Ankle pain lasting longer than three to six months.
Persistent health symptoms which remain unexplained after a complete medical evaluation. A cluster of symptoms that consistently appear together but without a known cause are referred to as a MEDICALLY UNEXPLAINED SYNDROME (MUS).
Acute myeloid leukemia not associated with cytogenetic abnormalities.
Narrowing of the vaginal orifice with a covering seal, occurring as a result of cutting and appositioning the labia minora and/or the labia majora, with or without excision of the clitoris for non medical reasons.
Acute otitis media which persists after one or two empiric antimicrobial courses of treatment.
A condition following an arterial switch operation to correct transposition of the great arteries, in which the old aortic root becomes the new pulmonary root and where outflow of blood from the right ventricle of the heart is obstructed at the level of the pulmonic valve.
An ossifying fibromyxoid tumor characterized by the presence of high grade nuclear features or increased cellularity and more than two mitotic figures per 50 HPFs.
A rare fatal amyloid disease in young people caused by a mutation in cystatin C. This condition predisposes towards intracerebral haemorrhage and dementia and is inherited in a dominant pattern.
This is a postprocedural heart valve disorder in which outflow of blood from the right ventricle of the heart is obstructed at the level of the pulmonic valve.
This refers to the postprocedural failure of the heart's tricuspid valve to close properly during systole. As a result, with each heart beat some blood passes from the right ventricle to the right atrium, the opposite of the normal direction.
Narrowing of the anterior nasal aperture (piriform or pyriform aperture), which is a pear-shaped opening in the skull that forms the bony inlet of the nose.
Edema in the region of the Lower eyelid.
Near the time of peak substance concentration after administration of a substance.
A benign or malignant tumor that arises from the testis. It is composed of granulosa cells, Leydig cells, Sertoli cells, and fibroblasts. Each of these cell types may constitute the only cellular component that is present in the tumor or it may be mixed with other cell types in various combinations. The prognosis can not always be predicted on histologic grounds alone. Approximately, ten percent of these tumors may metastasize. Representative examples include granulosa cell tumor, Leydig cell tumor, Sertoli cell tumor, and tumors of the thecoma-fibroma group.
A delay in closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life.
Slow escape rhythm associated with haemodynamic collapse.
Nonsyndromic premature fusion of a single suture.
Condition with either the sacralisation of the lowest lumbar segment or the lumbarisation of the most superior sacral segment of the spine.
A person's ability to walk between locations in a room.
Acquired angioedema due to activation of the classical complement pathway related to an underlying lymphoreticular disorder particularly lymphoma or monoclonal gammopathy of unknown significance (MGUS)
A less common type of cerebral palsy defined by decreased and/or fluctuating muscle tone; multiple forms of non-spastic cerebral palsy are each characterized by particular impairments; one of the main characteristics of non-spastic cerebral palsy is involuntary movement. Subtypes include ataxic and dyskinetic forms.
Condition where the ulna projects more distally relative to the radius.
A condition following an arterial switch operation to correct transposition of the great arteries, in which the old pulmonary root becomes the new aortic root and where the new aortic valve does not prevent backflow to the left ventricle.
An exceptionally rare adenocarcinoma that arises from the rete ovarii.
An intermediate, rarely metastasizing blood vessel neoplasm that more frequently affects young adult males and usually arises in the lower limbs. In approximately half of the affected patients the tumor is painful and in two-thirds of the patients the tumor is multifocal. Morphologically it is characterized by the presence of sheets and fascicles of spindle cells with abundant eosinophilic cytoplasm and vesicular nuclei. Cytologic atypia is usually mild. Approximately 60% of the patients develop local recurrences or additional tumors in the same anatomic region.
A subjective response indicating that something is mostly false.
A response indicating a high level of satisfaction.
A response indicating the absence of sexual activity.
An indication that something has very little quality, value or worth.
Showing many obvious signs of deterioration or decline.
A response indicating that something is a little worse.
A subjective response that something happens daily or almost daily.
An indication that something is scheduled, or occurs, less than once a month.
A response indicating that something happens or happened infrequently.
A response indicating that an individual is able to do something with much difficulty.
A response indicating that an individual is able to do something without any difficulty.
A subjective response indicating that something is definitely false.
A subjective response indicating that something is mostly true.
A subjective response indicating that something is definitely true.
A subjective response indicating that an individual finds something to be somewhat difficult.
A response indicating that it has been less than one year since an individual smoked a cigarette.
A response indicating that something happens or happened on one or two days.
A subjective response indicating that something is somewhat false.
A subjective response indicating that something is somewhat true.
A response indicating that an individual is in slight disagreement with something.
A response indicating that an individual is in slight agreement with something.
A response indicating that an individual is able to do something with a little difficulty.
A response indicating that something happened less than half the time.
A response indicating a moderate level of satisfaction.
A response indicating an equal level of satisfaction and dissatisfaction.
A response indicating a moderate level of dissatisfaction.
A response indicating a high level of dissatisfaction.
A response indicating that something is or was very difficult.
A subjective response indicating that an individual finds something to be extremely difficult.
A response indicating that something is or was not difficult.
A response indicating that something is or was slightly difficult.
A response indicating that sexual intercourse was not attempted.
A response indicating that 7 to 10 hours were spent on an activity.
A response indicating that 4 to 6 hours were spent on an activity.
A response indicating that an individual experiences or experienced something on some days.
A response indicating that something happens or happened almost all of the time.
A response indicating that an individual is able to do something with some difficulty.
A response indicating that an individual is able to do something for the smallest amount of effort or duration of time.
A response indicating that something happened always or almost always.
A response indicating that something happened never or almost never.
An indication that something is possible, but not uncertain.
A response indicating that something was occurring or recurring nearly continually without interruption.
A subjective answer of non-agreement regarding the importance of something.
A subjective answer of mild agreement regarding the importance of something.
A subjective answer of very strong agreement regarding the importance of something.
No apparent change or worsening in tumor staging classification.
An indication that something occurs or occurred less than once a week.
An indication that something occurs or occurred three or more times a week.
An indication that something occurs or occurred once or twice a week.
Locally advanced cancer that has spread to nearby organs but not to distant anatomic sites. The definition of stage IIID depends on the particular type of cancer that it refers to; for example, for cutaneous melanoma, stage IIID is defined as follows: T4b, N3a/b/c, M0. T4b: Tumor measuring more than 4.0 mm in thickness. Ulceration status: With ulceration. N3a: Four or more clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. N3b: Four or more nodal metastases, at least one of which was clinically detected, or presence of any number of matted nodes. Presence of in-transit, satellite, and/or microsatellite metastases: No. N3c: Two or more clinically occult nodal metastases. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. M0: No evidence of distant metastasis. LDH level is not applicable. (partially adapted from AJCC 8th ed.)
Indicates that an assessment was not performed.
A nitrogen oxoanion that is formed when nitrous acid is deprotonated. As nitrite is a metabolic end product for nitric oxide (NO), which is increased during inflammation; nitrite levels can be used to assess NO production and thus inflammation.
Iron ion requiring three electrons to return to its elemental state.
An active immunizing vaccine used to prevent infection by the bacterium Streptococcus pneumoniae. It is indicated for disease caused by serotypes 1, 5, 4, 6B, 7, 9V, 14, 18C, 19F, and 23F.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP2E1.
A neurological disorder in which a sensory stimulus, usually tactile but more rarely other sensory modalities, is misperceived in a location distant from the original stimulus.
Cortical malformations secondary to abnormal cortical maturation after CELL MIGRATION in NEUROGENESIS. This group includes injury to the cortex during later stages of cortical development such as POLYMICROGYRIA and focal cortical dysplasias.
Cortical malformations secondary to abnormal neuronal and glial CELL PROLIFERATION or APOPTOSIS in NEUROGENESIS. This group includes congenital MICROCEPHALIES; MICROLISSENCEPHALIES, megalencephalies, HEMIMEGALENCEPHALIES and cortical dysplasias with balloon cells.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP3A.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP2D6.
Any substance capable of causing an increase in the synthesis of cytochrome P450 2C9.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP2C19.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP2C8.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP2B6.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 CYP1A2.
Drugs and compounds that induce the synthesis of CYTOCHROME P-450 ENZYMES.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP3A.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2E1.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2D6.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C19.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C9.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2C8.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2B6.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP1A2.
Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 ENZYMES.
Morphological abnormalities of the cervical EPITHELIUM, usually revealed in PAP SMEAR, which do not meet the criteria for squamous CERVICAL INTRAEPITHELIAL NEOPLASIA or SQUAMOUS CELL CARCINOMAS of the CERVIX . It may be a sign of infection with certain types of human papillomavirus (HPV).or sign of a benign (not cancer) growth, such as a cyst or polyp or, in menopausal women, of low hormone levels. More testing, such as HPV test, may be needed.
Compounds and drugs that inhibit ligand binding or cellular signaling by BRADYKININ B1 RECEPTORS.
Compounds and drugs that inhibit ligand binding or cellular signaling by BRADYKININ RECEPTORS.
Compounds and drugs that bind to and inhibit or block the activation of ENDOTHELIN B RECEPTORS.
Compounds and drugs that bind to and inhibit or block the activation of DOPAMINE D2 RECEPTORS.
Compounds and drugs that block or inhibit the enzymatic action of AROMATIC AMINO ACID DECARBOXYLASES. Pharmaceutical agents in this category are used in conjunction with LEVODOPA in order to slow its metabolism.
Compounds and drugs that inhibit or block the activity of CCR5 RECEPTORS.
Substances and drugs that stimulate the synthesis or increase the activity of CARBAMOYL PHOSPHATE SYNTHETASE I. Drugs in this class of compounds have been used to treat the genetic disorder, CARBAMOYL-PHOSPHATE SYNTHASE I DEFICIENCY DISEASE.
Substances that bind to and sequester CALCIUM ions.
Compounds and drugs that inhibit ligand binding or cellular signaling by BRADYKININ B2 RECEPTORS.
Compounds that stimulate the activity of AMYMIN RECEPTORS. Included under this heading is the endogenous form of ISLET AMYLOID POLYPEPTIDE and synthetic compounds that mimic its effect.
Compounds that bind to and inhibit enzymes involved in the synthesis of STEROIDS.
Compounds that block release of the neurotransmitter ACETYLCHOLINE.
Compounds that bind to and inhibit the enzymatic activity of acetaldehyde dehydrogenases.
Compounds used to lower excessive POTASSIUM levels in the body.
Sudden death from overwork, most often as a result of acute CARDIOVASCULAR STROKE.
Sudden liver failure in the presence of underlying compensated chronic LIVER DISEASE (e.g., LIVER CIRRHOSIS; HEPATITIS; and liver injury and failure) due to a precipitating acute hepatic insult.
A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION, POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.
Malformation of external portion of EAR AURICLE.
Specific effects of drugs and substances on metabolic pathways such as those occurring through the CYTOCHROME P-450 ENZYME SYSTEM. These include effects that often result in DRUG INTERACTIONS; FOOD-DRUG INTERACTIONS; and HERB-DRUG INTERACTIONS.
A cytological test finding often from PAP SMEARS that shows abnormal lesions of SQUAMOUS EPITHELIAL CELLS of the CERVIX. It is a diagnostic criterion used in the Bethesda System for UTERINE CERVICAL NEOPLASMS and represents the PAP TEST result that is abnormal. Although squamous intraepithelial lesions test result does not mean UTERINE CERVICAL NEOPLASMS it requires follow-ups (e.g., HPV DNA TESTS; and COLPOSCOPY).
Morphological findings useful in differentiation and classification of results in CYTODIAGNOSIS and related techniques.
Compounds and drugs that bind to and block or inhibit the activation of ESTROGEN RECEPTORS.
Drugs that are designed to block the action of VIRAL FUSION PROTEINS and prevent VIRUSES from entering the cell.
Compounds and drugs that react with CYSTINE and convert it into a compound that can be more easily metabolized or intracellularly transported. Drugs in this class have been used to treat CYSTINOSIS.
Compounds that inhibit or block the activity of GLYCOSIDE HYDROLASES such as ALPHA-AMYLASES and ALPHA-GLUCOSIDASES.
An orally bioavailable indolocarbazole derivative and inhibitor of constitutively active mutant forms of FMS-like tyrosine kinase 3 (FLT3) with potential antineoplastic activity. Following administration, FLT3 tyrosine kinase inhibitor TTT-3002 binds to and inhibits ligand-dependent dimerization and autophosphorylation of mutant forms of FLT3 with constitutively activating mutations, including FLT3 internal tandem duplication (FLT3/ITD) and the activating point mutation D835Y. Prevention of autophosphorylation inhibits uncontrolled FLT3 signaling and may result in the inhibition of proliferation in tumor cells expressing constitutively active mutant forms of FLT3. The ability of TTT-3002 to inhibit FLT3 proteins with activating point mutations may result in increased efficacy because the activity of these mutants are resistant to other FLT3 kinase inhibitors. FLT3, a tyrosine kinase receptor, plays a role in the regulation of hematopoietic progenitor cell proliferation, and in leukemic cell proliferation and survival. Constitutively activating mutations of FLT3 are the most frequent genetic alterations in acute myeloid leukemia.
A proprietary recombinant bispecific T-cell engager (BiTE) antibody composed of two single-chain variable fragments (scFv), one directed against the tumor-associated antigen (TAA) CD33 fused to one that is directed against the CD3 antigen found on T-lymphocytes, with potential immunostimulating and antineoplastic activities. Upon administration of anti-CD33/CD3 BiTE antibody AMG 330, this bispecific antibody binds to both the CD3 antigen on cytotoxic T-lymphocytes (CTLs) and the CD33 antigen found on CD33-expressing tumor cells. This activates and redirects CTLs to CD33-expressing tumor cells, which results in the CTL-mediated cell death of CD33-expressing tumor cells. CD33, a myeloid differentiation antigen, is expressed on normal non-pluripotent hematopoietic stem cells and overexpressed on neoplastic cells in patients with acute myeloid leukemia.
An orally available inhibitor of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) replication complex, with potential activity against HCV. Upon oral administration and after intracellular uptake, ledipasvir binds to and blocks the activity of the NS5A protein. This results in the disruption of the viral RNA replication complex, blockage of HCV RNA production, and inhibition of viral replication. NS5A, a zinc-binding and proline-rich hydrophilic phosphoprotein, plays a crucial role in HCV RNA replication. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family; HCV infection is associated with the development of hepatocellular carcinoma (HCC).
A non-nucleoside inhibitor of the hepatitis C virus (HCV) non-structural protein 5B (NS5B), an RNA-dependent RNA polymerase, with potential activity against HCV. Upon administration and after intracellular uptake, dasabuvir binds HCV NS5B polymerase and blocks viral RNA synthesis and replication. The HCV NS5B protein is essential for the replication of the HCV RNA genome. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family; HCV infection is associated with the development of hepatocellular carcinoma (HCC).
An orally available, piperidinone inhibitor of MDM2 (murine double minute 2), with potential antineoplastic activity. Upon oral administration, MDM2 inhibitor AMG-232 binds to MDM2 protein and prevents its binding to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this MDM2-p53 interaction, the transcriptional activity of p53 is restored. This leads to p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger protein and a negative regulator of the p53 pathway, is overexpressed in cancer cells; it plays a key role in cancer cell proliferation and survival.
An orally bioavailable inhibitor of the class I phosphatidylinositol 3-kinase (PI3K) beta isoform with potential antineoplastic activity. PI3K beta inhibitor SAR260301 selectively inhibits PI3K beta kinase activity in the PI3K/Akt/mTOR pathway, which may result in apoptosis and growth inhibition in PI3K beta-expressing and/or phosphatase and tensin homolog (PTEN)-deficient tumor cells. Dysregulation of the PI3K/Akt/mTOR pathway is frequently found in solid tumors and contributes to increased tumor cell growth, tumor cell survival, and resistance to both chemotherapy and radiotherapy. PI3K beta is the p110-beta catalytic subunit of the class I PI3K. PTEN, a tumor suppressor protein and negative regulator of PI3K activity, is often mutated in a variety of cancer cells. By specifically targeting class I PI3K beta, this agent may be more efficacious and less toxic than pan-PI3K inhibitors.
An orally bioavailable protein tyrosine kinase inhibitor for FMS-related tyrosine kinase 3 (FLT3; STK1) and stem cell factor receptor (SCFR; KIT), with potential antineoplastic activity. FLT3/KIT kinase inhibitor AKN-028 binds to and inhibits both the wild-type and mutated forms of FLT3 and SCFR. This may result in an inhibition of tumor cell proliferation in cancer cell types that overexpress these receptor tyrosine kinases.
An orally available inhibitor of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) replication complex, with potential activity against HCV. Upon oral administration and after intracellular uptake, ombitasvir binds to and blocks the activity of the NS5A protein. This results in the disruption of the viral RNA replication complex, blockage of HCV RNA production, and inhibition of viral replication. NS5A, a zinc-binding and proline-rich hydrophilic phosphoprotein, plays a crucial role in HCV RNA replication. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family; HCV infection is associated with the development of hepatocellular carcinoma (HCC).
An orally available, small molecule inhibitor of CRM1 (chromosome region maintenance 1 protein, exportin 1 or XPO1), with potential antineoplastic activity. Selinexor modifies the essential CRM1-cargo binding residue cysteine-528, thereby irreversibly inactivates CRM1-mediated nuclear export of cargo proteins such as tumor suppressor proteins (TSPs), including p53, p21, BRCA1/2, pRB, FOXO, and other growth regulatory proteins. As a result, this agent, via the approach of selective inhibition of nuclear export (SINE), restores endogenous tumor suppressing processes to selectively eliminate tumor cells while sparing normal cells. CRM1, the major export factor for proteins from the nucleus to the cytoplasm, is overexpressed in a variety of cancer cell types.
An alpha-folate receptor (aFR)-mediated inhibitor of thymidylate synthase (TS), with potential antineoplastic activity. Upon intravenous infusion, ONX-0801 selectively targets and binds to aFR-expressing tumor cells. Upon uptake by aFR, this agent binds to and inhibits TS. This reduces thymine nucleotide synthesis, inhibits both DNA synthesis and cell division, and leads to tumor cell apoptosis. TS catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), an essential precursor for DNA synthesis, and plays a key role in cell growth and division. aFR, a cell-surface receptor glycoprotein, is overexpressed on various tumor cell types, but is minimally expressed by normal, healthy tissue.
An orally active, benzodiazepine type, selective cholecystokinin B receptor (CCKBR; CCK2R; gastrin receptor) antagonist with potential gastric acid reducing and antiproliferative activity. Upon administration, netazepide, selectively binds to and blocks the CCKBR, thereby preventing the binding of gastrin and cholecystokinin. This may prevent gastric neuroendocrine enterochromaffin-like (ECL) cell-induced secretion of histamine, ultimately preventing gastric acid secretion from adjacent parietal cells. In addition, YF476 may inhibit ECL cell proliferation and ECL-derived gastric carcinoids.
An orally available cyclin-dependent kinase (CDK) inhibitor that targets the CDK4 (cyclin D1) and CDK6 (cyclin D3) cell cycle pathway, with potential antineoplastic activity. Abemaciclib specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation in early G1. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of the serine/threonine kinases CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation.
An orally bioavailable, CaV3.2 T-type calcium channel blocker with potential anti-hyperalgesic activity. Upon oral administration, ABT-639 selectively binds to and blocks the CaV3.2 isoform of the low voltage-gated T-type calcium channels located in peripheral sensory neurons. This prevents the influx of calcium ions into the cell upon membrane depolarization. The inhibition of both neuronal hyperexcitability and firing of nociceptive, peripheral sensory neurons induces an anti-nociceptive effect. The expression of the CaV3.2 T-type channels plays a key role in nociceptive and neuropathic pain.
An orally bioavailable, non-nucleoside, 3,4-dihydroquinazolinyl acetic acid and inhibitor of the pUL56 subunit of the viral terminase complex of cytomegalovirus (CMV), with potential CMV-specific antiviral activity. Upon oral administration, letermovir binds to the pUL56 subunit of the viral terminase complex of CMV and prevents the cleavage of concatemeric DNA into monomeric genome length DNA. As this agent interferes with viral DNA processing and subsequent viral DNA packaging into procapsids, CMV replication is blocked and CMV infection is prevented.
Lipedema with secondary LYMPHEDEMA involvement.
An unusual desire or craving for abnormal foods.
A subjective response indicating that something is moderately good.
Body Mass Index (kg/m²) from 35.00 to 39.99 (WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. WHO Technical Report Series 854. Geneva: World Health Organization, 1995).
Body Mass Index (kg/m²) from 30.00 to 34.99 (WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. WHO Technical Report Series 854. Geneva: World Health Organization, 1995).
An aluminum salt with immune adjuvant activity. This agent adsorbs and precipitates protein antigens in solution; the resulting precipitate improves vaccine immunogenicity by facilitating the slow release of antigen from the vaccine depot formed at the site of inoculation.
A condition in newborns caused by immunity of the mother to PLATELET ALLOANTIGENS on the fetal platelets. The PLATELETS, coated with maternal ANTIBODIES, are destroyed and removed by the fetal MONONUCLEAR PHAGOCYTE SYSTEM. Affected infants may have INTRACRANIAL HEMORRHAGES.
An orally available cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. Palbociclib selectively inhibits cyclin-dependent kinase 4 (CDK4) and 6 (CDK6), thereby inhibiting retinoblastoma (Rb) protein phosphorylation early in the G1 phase leading to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of cell cycle progression.
A recombinant, single-chain, anti-CD19/anti-CD3 bispecific monoclonal antibody with potential immunostimulating and antineoplastic activities. Blinatumomab possesses two antigen-recognition sites, one for the CD3 complex, a group of T cell surface glycoproteins that complex with the T cell receptor (TCR), and one for CD19, a tumor-associated antigen (TAA) overexpressed on the surface of B cells. This bispecific monoclonal antibody brings CD19-expressing tumor B-cells and cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) together, which may result in the CTL- and HTL-mediated cell death of CD19-expressing B-lymphocytes.
Steroid sulfatase inhibitor BN 83495 selectively binds to and inhibits steroid sulfatase (STS), which may inhibit the production of locally active estrogens and so inhibit estrogen-dependent cell growth in tumor cells, such as those of the breast, ovary, and endometrium. STS is a cytoplasmic enzyme responsible for the conversion of circulating inactive estrone sulfate and estradiol sulfate to biologically active unconjugated estrone and estradiol, respectively.
An orally available inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with antineoplastic activity. Upon administration, alectinib binds to and inhibits ALK kinase, ALK fusion proteins as well as the gatekeeper mutation ALKL1196M known as one of the mechanisms of acquired resistance to small-molecule kinase inhibitors. The inhibition leads to disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-overexpressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. ALK dysregulation and gene rearrangements are associated with a series of tumors.
Pre-renal acute kidney injury (AKI), also called acute renal failure, occurs when a sudden reduction in blood flow to the kidney (renal hypoperfusion) causes a loss of kidney function. In pre-renal acute kidney injury, there is nothing wrong with the kidney itself.
A congenital, hairless plaque consisting of overgrown epidermis, sebaceous glands, hair follicles, apocrine glands and connective tissue. They are a variant of epidermal naevi. Sebaceous naevi most often appear on the scalp, but they may also arise on the face, neck or forehead. At birth, a sevaceous nevus typically appears as a solitary, smooth, yellow-orange hairless patch. Sebaceous naevi become more pronounced around adolescence, often appearing bumpy, warty or scaly.
The presence of one or more bullae on the skin of the genital region, defined as fluid-filled blisters more than 5 mm in diameter with thin walls.
A rare life threatening acquired neurologic disease with characteristics of neuromyotonia, dysautonomia and encephalopathy with severe insomnia. Signs involving central (e.g. hallucinations, confusion, amnesia, myoclonus), autonomic (e.g. variations in blood pressure, hyperhidrosis) and peripheral (e.g. painful cramps, myokymia) hyperactivity, as well as systemic manifestations (such as weight loss, pruritus, fever), are reported. Thymoma is present in some cases.
Abnormal raised concentration of ferritin, a ubiquitous intracellular protein that stores iron, in the blood.
A rare syndrome characterized by telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. It is best classified as a type of plasma cell dyscrasia with paraneoplastic manifestations.
Pinhole-sized concave depressions with hyperkeratosis in the skin of a finger or toe.
A type of anemia cahracterized by abnormally large erythrocytes with abnormally high amounts of haemoglobin.
The average blood pressure reading in the pulmonary artery as calculated through multiple cardiac cycles.
A nutritional supplement containing the L-threonate form of magnesium (Mg) that can be used to normalize Mg levels in the body. Upon administration, Mg is utilized by the body for many biochemical functions and reactions including: bone and muscle function, protein and fatty acid formation, activation of B vitamins, blood clotting, insulin secretion, and ATP formation. Mg also serves as a catalyst for many enzymes throughout the body. In addition, magnesium improves the functioning of the immune system by enhancing the expression of natural killer activating receptor NKG2D in cytotoxic T-lymphocytes and natural killer (NK) cells. This increases their anti-viral and anti-tumor cytotoxic effects.
Fingers appear swollen and plump owing to inflammation of the complete finger.
An orally bioavailable, synthetic acylsulfonamide inhibitor of the hepatitis C virus (HCV) protease complex comprised of non-structural protein 3 and 4A (NS3/NS4A), with potential activity against HCV genotype 1. Upon administration, paritaprevir reversibly binds to the active center and binding site of the HCV NS3/NS4A protease and prevents NS3/NS4A protease-mediated polyprotein maturation. This disrupts both the processing of viral proteins and the formation of the viral replication complex, which inhibits viral replication in HCV genotype 1-infected host cells. NS3, a serine protease, is essential for the proteolytic cleavage of multiple sites within the HCV polyprotein and plays a key role during HCV ribonucleic acid (RNA) replication. NS4A is an activating factor for NS3. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family, and infection is associated with the development of hepatocellular carcinoma (HCC).
An orally bioavailable combination agent containing ombitasvir, an inhibitor of the hepatitis C virus (HCV) non-structural protein 5A (NS5A) replication complex, paritaprevir, a synthetic acylsulfonamide inhibitor of the HCV protease complex comprised of non-structural protein 3 and 4A (NS3/NS4A), and the cytochrome P450 (CYP) 3A4 inhibitor ritonavir, with potential activity against HCV. Upon oral administration of ombitasvir/paritaprevir/ritonavir, ombitasvir, enters the cell and binds to and blocks the activity of the NS5A protein. This results in the disruption of the viral RNA replication complex, blockage of HCV RNA production, and inhibition of viral replication. After intracellular uptake, paritaprevir reversibly binds to the active center and binding site of the HCV NS3/NS4A protease and prevents NS3/NS4A protease-mediated polyprotein maturation. This disrupts both the processing of viral proteins and the formation of the viral replication complex, which inhibits viral replication in HCV genotype 1-infected host cells. Although ritonavir is not active against HCV, it strongly inhibits the activity of CYP3A4, thereby blocking the degradation of paritaprevir, which is a CYP3A4 substrate. This leads to an increased concentration and half-life of paritaprevir as compared to the administration of paritaprevir without ritonavir. NS5A, a zinc-binding and proline-rich hydrophilic phosphoprotein, plays a crucial role in HCV RNA replication. NS3, a serine protease essential for the proteolytic cleavage of multiple sites within the HCV polyprotein, plays a key role during HCV ribonucleic acid (RNA) replication. NS4A is an activating factor for NS3. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family, and infection is associated with the development of hepatocellular carcinoma (HCC).
A mycosis fungoides/Sezary syndrome stage defined as follows: T1-4, N0-2, M0, B2. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. T3: One or more tumors (equal or greater than 1 cm in diameter). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B2: High blood tumor burden: 1,000 per microliter or more Sezary cells with positive clone. (AJCC 8th ed.)
A mycosis fungoides/Sezary syndrome stage defined as follows: T1-4, N3, M0, B0-2. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. T3: One or more tumors (equal or greater than 1 cm in diameter). T4: Confluence of erythema covering 80% or more of body surface area. N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. B2: High blood tumor burden: 1,000 per microliter or more Sezary cells with positive clone. (AJCC 8th ed.)
A stage term referring to Hodgkin or non-Hodgkin lymphoma involving a single extralymphatic site in the absence of nodal involvement. (from AJCC 8th Ed.)
Alteration to skin and/or mucous membrane epithelial integrity manifest by vesicular inflammation and superficial ulceration. These may be a result of disease that presents with cell and/or humoral immunity-mediated attack on epithelial-connective tissue targets.
Underdevelopment of the alveolar process (also known as alveolar bone).
An idiopathic glomerular disease characterised by massive accumulation of atypical type III collagen fibrils within the mesangial matrix and subendothelial space of glomeruli.
Child at risk of being neglected by others.
Inflammation of the gingivae and oral mucosa due to contact with irritants or allergens but without specification of which mechanism is involved.
High muscle attachment in the mouth resulting in abnormal pull on the gingiva leading to gingival recession and/or inflammation.
Structural abnormality of a valve in which the valve opening is narrowed and the valve fails to close properly.
Mild Asperger's syndrome present in an adult.
A patient speculated to have Ebola virus disease (EVD) based on symptomatology and history of exposure to the Ebola virus
A patient without symptomatology or history to suggest concern for EVD.
Someone who has been determined to be at high risk for developing EVD. This may include criteria such as CDC: 1) Percutaneous or mucous membrane exposure to blood or body fluids of an EVD patient; 2) Direct skin contact with, or exposure to blood or body fluids of, an EVD patient without appropriate personal protective equipment (PPE); 3) Processing blood or body fluids of a person with Ebola while the person was symptomatic without appropriate PPE or standard biosafety precautions; 4) Direct contact with a dead body without appropriate PPE in a country where an EVD outbreak is occurring; 5) Having lived in the immediate household and provided direct care to a person with Ebola while the person was symptomatic.
Someone who has been determined to be at low risk for developing EVD. This may include criteria such as CDC: 1) Having been in a country with widespread Ebola virus transmission within the past 21 days and having had no known exposures; 2) Direct contact while using appropriate personal protective equipment (PPE) with a person with Ebola while the person was symptomatic; 3) Brief proximity with a person with Ebola while the person was symptomatic; 4) Traveled on an aircraft with a person with Ebola while the person was symptomatic.
A person with no known exposure to Ebola virus. This includes anyone who has been in a country in which an EVD outbreak occurred within the past 21 days and has had no high or low risk exposures to the Ebola virus.
Based on symptomatology, the patient requires hospitalisation
Based on symptomatology, the patient does not require hospitalisation
Ability to perform activities to care for one's body and bodily functions
Gingival disease with an aetiology other than dental plaque, such as bacterial, viral, fungal or genetic origin, due to systemic conditions, trauma, foreign body reactions, or other causes.
Associates gingival fibromatosis with dental abnormalities including generalised thin hypoplastic amelogenesis imperfecta, intrapulpal calcifications and delay of tooth eruption.
A very rare malignant lung tumor with myoepithelial differentiation.
A small vessel vasculitis restricted to the lungs that may induce diffuse alveolar haemorrhage without any underlying systemic disease.
Lupus erythematosus affecting oral mucosa. This may be associated with either cutaneous or systemic lupus erythematosus and presents most commonly as mucosal ulceration.
A form of chronic oral candidosis involving multiple oral sites with angular cheilitis, retrocommissural leukoplakia, median rhomboid glossitis and palatal lesions.
Illnesses due to micro-organisms and chemicals in drinking water, those caused by organisms having part of their lifecycle in water or those with water-related vectors, and others spread by aerosols containing pathogens.
A natural tooth that will be used as a retainer for a fixed prosthesis. A tooth that may have had limited previous treatment or is not perfectly aligned.
The condition of a natural tooth as it relates to its position and strength to serve as an abutment for a fixed prosthesis.
A natural tooth that will be used as a retainer for a fixed prosthesis. A tooth that is well aligned, but has had previous restorations or other damage to 4 or more sextants of the tooth that reduce its potential strength.
A bacterial infection by Listeria monocytogenes in a sterile body compartment.
A natural tooth that will be used as a retainer for a fixed prosthesis. A tooth that is well aligned, but has had previous restorations or other damage in 1 or 2 sextants of the tooth that reduce its potential strength.
A natural tooth that will be used as a retainer for a fixed prosthesis. A tooth that is well aligned, but has had previous restorations or other damage in 3 sextants of the tooth that reduce its potential strength.
A natural tooth that will be used as a retainer for a fixed prosthesis. A tooth that is well aligned with no previous restorations or other damage that would compromise its strength.
Continuous atrial fibrillation of greater than 12 months duration.
Partial progress has been made towards the targeted objective.
There has been some digression away from the targeted objective.
No progress has been made towards the targeted objective.
The targeted objective cannot be achieved.
Intimate partner abuse is defined as physical, sexual or psychological harm perpetrated by a current or former partner. The abuse can occur among heterosexual or same-sex couples and does not require sexual intimacy.
At risk of intimate partner abuse which is defined as physical, sexual or psychological harm perpetrated by a current or former partner. The abuse can occur among heterosexual or same-sex couples and does not require sexual intimacy.
ST segment elevation in leads II and/or III and/or aVF with ST segment elevation in V3R and/or V4R.
Laterognathia is understood as a lateral crossbite of individual or all side teeth with mandibular dislocation of the lower jaw's centre.
The caregiver's attitude conflicts with the patient and/or the treatment plan.
ST segment elevation in leads II and/or III and/or aVF.
ST segment elevation in lead I and/or precordial leads V5-8 and/or aVL.
ST segment elevation in precordial leads.
ST segment elevation in precordial leads (V2-5) with ST segment elevation in leads II and/or III and/or aVF.
ST segment depression in posteriorly placed precordial leads (V7-10).
ST segment elevation in leads I and/or aVL with ST segment elevation in leads II and/or III and/or aVF.
ST segment depression seen in multiple regions, including anterior, lateral and inferior.
ST segment depression in leads II and/or III and/or aVF.
At risk of negative quality of life in terms of health and happiness, measured by a person's ability to enjoy normal life activities.
Nurse controlled analgesia is a technique by which the nurse or health professional licensed to administer medications, gives the patient a pre-programmed amount of an intravenous or subcutaneous analgesic solution as a bolus dose by the press of a button.
Failure to follow the predictable course of grieving to resolution.
Traditional therapy is often called complementary or alternative therapy. It is the knowledge, skills and practices based on the theories, beliefs, and experiences indigenous to different cultures used in the maintenance of health and prevention, diagnosis, improvement or treatment of physical and mental illness.
A ureterocele that is located entirely within the bladder, and which may be associated with a single system, with the upper pole ureter of a completely duplicated system, or rarely associated with a lower pole ureter. (Adapted from Glassberg KI, Braren V, Duckett JW, Jacobs EC, King LR, Lebowitz RL et al. Suggested terminology for duplex systems, ectopic ureters and ureteroceles. J Urol 1984; 132(6):1153-1154.)
Potential for shallow breaths or breathing pauses lasting from a few seconds to minutes usually occurring during sleep.
A purposeful and often repeated attempt to leave a healthcare setting.
Mental and physical fatigue from prolonged or difficult treatment.
Potential for the attitudes from the aspects of a religion to affect or guide the course of healthcare treatment recommendations or advice.
Potential for inadequate circulation of blood causing decreased oxygenation to tissues resulting in cellular injury and inadequate tissue function.
Potential for inadequate physiological activity of the heart to maintain adequate transportation and oxygenation of blood to the body.
On dialysis to treat acute renal failure.
Potential for inadequate physiological activity allowing the exchange of oxygen and carbon dioxide via cellular and external respirations to maintain the body's needs.
Potential for inadequate physiological activity of the central and/or peripheral nervous system to maintain normal affective, cognitive and neuromuscular function.
The presence of inflammation of the skin. That is, an abnormality of the skin resulting from the local accumulation of fluid, plasma proteins, and leukocytes. [HPO:probinson]
Physical stance often assumed by people experiencing respiratory distress or who are simply out of breath. In this position, a person sits or stands leaning forward and supports the upper body with hands on knees or other surface.
A rare solid tumor like condition seen in young women, characterized by an accumulation of fluid within the ovarian stroma separating normal follicular structures.
A way for prescriptions for medical practitioners to be ordered by phone call to pharmacy
Glycopeptides that have an additional lipophilic side chains. Several semisynthetic lipoglycopeptide antibiotics are derived from naturally occurring lipoglycopeptide and glycopeptide antibiotics.
An orally bioavailable, small-molecule, ATP-competitive inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity. Fedratinib competes with JAK2 as well as the mutated form AK2V617F for ATP binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-STAT signaling pathway, and the induction of tumor cell apoptosis. JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders (MPDs); the mutated form JAK2V617F has a valine-to-phenylalanine modification at position 617 and plays a key role in tumor cell proliferation and survival.
An orally bioavailable small-molecule smoothened (Smo) antagonist with potential antineoplastic activity. Sonidegib selectively binds to the hedgehog (Hh)-ligand cell surface receptor Smo, which may result in the suppression of the Hh signaling pathway and, so, the inhibition of tumor cells in which this pathway is abnormally activated. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair. Inappropriate activation of Hh pathway signaling and uncontrolled cellular proliferation, as is observed in a variety of cancers, may be associated with mutations in the Hh-ligand cell surface receptor Smo.
An alkoxyalkyl ester prodrug containing the synthetic, acyclic nucleoside monophosphate analog cidofovir linked, through its phosphonate group, to a lipid, 3-hexadecyloxy-1-propanol, with antiviral activity against double-stranded DNA viruses. Upon oral administration, brincidofovir crosses the intestinal wall and penetrates target viral-infected cells before being cleaved to the free antiviral agent cidofovir. In turn, cidofovir is phosphorylated by pyruvate kinases to its active metabolite cidofovir diphosphate. Cidofovir diphosphate, bearing structural similarity to nucleotides, competes with deoxycytosine-5-triphosphate (dCTP) for viral DNA polymerase and gets incorporated into the growing viral DNA strands. As a result, it prevents further DNA polymerization and disrupts DNA replication of viruses. Compared to cidofovir, which is given intravenously, hexadecyloxypropyl-cidofovir shows better oral bioavailability, less toxicity and enhanced cellular penetration.
An orally bioavailable specific oral inhibitor of the pan-class I phosphatidylinositol 3-kinase (PI3K) family of lipid kinases with potential antineoplastic activity. Buparlisib specifically inhibits class I PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway in an ATP-competitive manner, thereby inhibiting the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate and activation of the PI3K signaling pathway. This may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis. Dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.
A carcinoma that arises from the head and neck region. Representative examples include oral cavity squamous cell carcinoma, laryngeal squamous cell carcinoma, and salivary gland carcinoma.
Impression of infrequent or difficult passage of hard, dry feces without cause.
Migraine is the most common type of chronic, episodic headache, as summarized by Featherstone (1985). One locus for migraine with or without aura (MGR1) has been identified on chromosome 4q24. Other loci for migraine have been identified on 6p21.1-p12.2 (MGR3; 607498), 14q21.2-q22.3 (MGR4; 607501), 19p13 (MGR5; 607508), 1q31 (MGR6; 607516), 15q11-q13 (MGR7; 609179), 5q21 (with or without aura, MGR8, 609570; with aura, MGR9, 609670), 17p13 (MGR10; 610208), 18q12 (MGR11; 610209), 10q22-q23 (MGR12; 611706), and the X chromosome (MGR2; 300125). Mutation in the KCNK18 gene (613655) on chromosome 10q25 causes migraine with aura (MGR13; 613656). A subtype of autosomal dominant migraine with aura (MA), familial hemiplegic migraine (FHM; see 141500), is caused by mutation in the CACNA1A gene (601011) on chromosome 19p13 (FHM1; 141500), by mutation in the ATP1A2 gene (182340) on chromosome 1q21 (FHM2; 602481), or by mutation in the SCN1A gene (182389) on chromosome 2q24 (FHM3; 609634). Another locus for FHM has been mapped to chromosome 1q31 (FHM4; see 607516). There is evidence that a polymorphism in the estrogen receptor gene (ESR1; 133430.0005) and a polymorphism in the TNF gene (191160.0004) may confer susceptibility to migraine. A polymorphism in the endothelin receptor type A gene (EDNRA; 131243.0001) may confer resistance to migraine.
In postaxial polydactyly type A the extra digit is well formed and articulates with the fifth or an extra metacarpal.
Terminal broadening of the toes (distal phalanges of the toes).
A type of pleural effusion with a exudate (extravascular fluid that has exuded out of a tissue or its capillaries due to injury or inflammation). Pleural effusions can be classified as transudates or exudates based on Light's criteria, which classify an effusion as exudate if one or more of the following are present: (1) the ratio of pleural fluid protein to serum protein is greater than 0.5, (2) the ratio of pleural fluid lactate dehydrogenase (LDH) to serum LDH is greater than 0.6, or (3) the pleural fluid LDH level is greater than two thirds of the upper limit of normal for serum LDH.
German syndrome is an autosomal recessive arthrogryposis syndrome, described in 5 cases. Three of the four known families with affected children were Ashkenazi Jews. German syndrome is characterised by arthrogryposis, hypotonia-hypokinesia sequence, and lymphoedema. Patients present distinct craniofacial appearance (tall forehead and ''carp'' shaped mouth, cleft palate), contractures, and severe hypotonia manifesting as motor delay and swallowing difficulties. The disease has a severe morbidity and mortality rate and survivors present a small stature, hypotonia, frequent upper respiratory infections and psychomotor delay. There have been no further descriptions in the literature since 1987.
A developmental defect resulting in the presence of fewer than the normal number of digits.
A fluid filled sac in the kidney. [Eurenomics:fschaefer]
The prominence of the superficial vessels of the sclera or conjunctiva resulting in a red or pink appearance.
A bacterial infection by Listeria monocytogenes in a newborn infant up to 28 days old.
Excessive movement of muscles of the body as a whole, which may be associated with organic or psychological disorders.
Loss of vascularization and tissue death caused by the disruption in the arterial access. Common causes include trauma due to accidents, insect or reptile bites, severe cold exposure or pathological conditions such as infarctions or blood dyscrasias.
A mixed glioma that arises from the brain stem and occurs during childhood.
A gliosarcoma that arises from the brain stem and occurs during childhood.
A myxopapillary ependymoma that occurs during adulthood.
A neuroblastoma that arises from the cerebral hemispheres and occurs during childhood.
A pineoblastoma that occurs during childhood.
The reemergence of pineoblastoma in childhood after a period of remission.
Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD), which catalyzes the initial step of mitochondrial ß-oxidation of long-chain fatty acids with a chain length of 14 to 20 carbons, is associated with three phenotypes. The severe early-onset cardiac and multiorgan failure form typically presents in the first months of life with hypertrophic or dilated cardiomyopathy, pericardial effusion, and arrhythmias, as well as hypotonia, hepatomegaly, and intermittent hypoglycemia. The hepatic or hypoketotic hypoglycemic form typically presents during early childhood with hypoketotic hypoglycemia and hepatomegaly, but without cardiomyopathy. The later-onset episodic myopathic form presents with intermittent rhabdomyolysis provoked by exercise, muscle cramps and/or pain, and/or exercise intolerance. Hypoglycemia typically is not present at the time of symptoms.
A discontinuity of the skin exhibiting incomplete loss of the epidermis, a lesion that is moist, circumscribed, and usually depressed.
Keratosis follicularis spinulosa decalvans is an uncommon genodermatosis chiefly characterized by widespread keratosis pilaris, progressive cicatricial alopecia of the scalp, eyebrows, and eyelashes, and an excess of affected males. Photophobia, blepharitis/conjunctivitis, and corneal dystrophy are characteristic ancillary findings. It is most often inherited as an X-linked trait (summary by Castori et al., 2009). Autosomal dominant inheritance has also been reported (KFSD; 612843). The term 'cum ophiasi' means 'with ophiasis,' i.e., baldness in 1 or more winding streaks about the head, which comes from the Greek for snake. Decalvans refers to the loss of hair.
In the hand, osteoarthritis can develop in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints (Stefansson et al., 2003). Patients with osteoarthritis may have one, a few, or all of these sites affected. Heberden nodes are bony excrescences of the phalanges of the distal interphalangeal joints of the fingers (Stecher, 1955). They can be considered a variety of osteoarthrosis, or degenerative arthritis. For a phenotypic description and a discussion of genetic heterogeneity of osteoarthritis, see OS1 (165720).
A congenital anomaly characterized by a joining (fusion) of two or more cervical vertebral bodies with one another.
Limbus-to-limbus corneal thinning, often greatest in the periphery, with globular protrusion of the cornea.
The formation or development of an ulcer.
A broad classification of disorders which includes 6 subtypes (primary central sleep apnea, central sleep apnea due to Cheyne-Stokes breathing pattern, central sleep apnea due to medical condition not Cheyne-Stokes, central sleep apnea due to high-altitude periodic breathing, central sleep apnea due to drug or substance and primary sleep apnea of infancy) that are each characterized by interruptions in breathing while asleep. It is caused by improper signaling from the brainstem to respiratory muscles and is triggered by either hypoventilation or hyperventilation. In adults, this disorder may arise following a stroke, congestive heart failure, trauma, infection or the use of narcotic medications. It is more common in older males and may present as a co-morbid condition to obesity. Clinical signs include snoring, insomnia or hypersomnia, difficulty concentrating and fatigue. Recurrent episodes of hypoxia/hypoxemia have long-term detrimental effects on cardiovascular health.
Apnea resulting from depression of the respiratory centers in the medulla oblongata. There is a lack of respiratory effort rather than obstruction of airflow. [HPO:curators]
Interference or disruption of memory processes. Memory dysfunction refers to the inability to store and retrieve information. This term encompasses a large number of problems and issues associated with intellectual functioning. 2005
A type of subvalvular aortic stenosis resulting from thickening of the musculature of the interventricular septum, which results in obstruction to blood flow though the left-ventricular outflow tract.
A classification of rare, non-neoplastic, proliferative disorders of the hematologic system. Primary or familial hemophagocytic lymphohistiocytosis (HLH) is inherited with an autosomal recessive pattern with five known subtypes differentiated by specific genetic mutations. Secondary manifestation of HLH is usually seen in hyperactivated immunologic states such as infection, autoimmune disease or malignancy. Histiocytes in the bone marrow, spleen or lymph nodes become activated to the point that phagocytosis proceeds unchecked. Clinical signs usually present within the first decade and include fever, jaundice, hepatosplenomegaly, lymphadenopathy and skin rash. Prompt initiation of treatment improves survival though prognosis remains poor even with intervention.
The recombinant form of endogenous MIP-1 beta chemokine that chemoattracts both neutrophils and monocytes, stimulates macrophages, and stimulates myelopoietic cell growth.
A recombinantly produced form of the hormone parathyroid hormone-related protein. Endogenous parathyroid hormone-related protein regulates calcium usage in bone and mammary glands.
A novel dual inhibitor targeting human vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs) with antiangiogenic activity. Lucitanib inhibits VEGFR-1, -2, -3 and FGFR-1, -2 kinases in the nM range, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation, and the induction of tumor cell death. Both VEGFRs and FGFRs belong to the family of receptor tyrosine kinases that may be upregulated in various tumor cell types.
An old term for glycolysis. Often it is used to describe anaerobic glucose catabolism that includes the further conversion of PYRUVIC ACID to LACTIC ACID or ETHANOL.
A sleep disorder characterized by the repeated occurrence of frightening dreams which precipitate awakenings from sleep; on awakening, the individual becomes fully alert and oriented and has detailed recall of the nightmare, which usually involves imminent danger or extreme embarrassment to the individual.
Congenital hydrocephalus-1 is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). Genetic Heterogeneity of Congenital Hydrocephalus See also HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p23, and HYC3 (617967), caused by mutation in the WDR81 gene (614218) on chromosome 17p13. An X-linked form of congenital hydrocephalus (HSAS, HYCX; 307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28.
A state of unease characterized by diffuse motor activity or motion subject to limited control, nonproductive or disorganized behavior, and subjective distress.
A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.
Persistence of immune complexes in the blood circulation.
A thick, protein-rich substance secreted by the breasts during the second half of pregnancy and for a few days after birth before the breast milk comes in. It contains antibodies which serve to give the baby protection from disease and also has a laxative effect on the colon which helps to expel the plug of meconium and facilitate the establishment of normal bowel movements.
A clinical finding indicating less than normal growth in infancy.
Inflammation of the body fundic mucosa of the stomach. It results from the development of autoantibodies against the parietal and chief cells. It is associated with the presence of intestinal metaplasia and an increased risk of developing gastric carcinoma.
Proliferation of astrocytes in the area of a lesion of the central nervous system.
A microscopic finding indicating the presence of acute, subacute or chronic inflammation in a tissue sample.
A condition that is characterized by elevated serum IgE, dermatitis, and respiratory infections.
A synthetic phenylethylamine that mimics the sympathomimetic actions of the endogenous norepinephrine. Norepinephrine acts directly on the alpha- and beta-adrenergic receptors. Clinically, norepinephrine is used as a peripheral vasoconstrictor that causes constriction of arterial and venous beds via its alpha-adrenergic action. It is also used as a potent inotropic and chronotropic stimulator of the heart mediated through its beta-1 adrenergic action.
Disorder caused by an interruption of the mineralization of organic bone matrix leading to bone softening, bone pain, and weakness. It is the adult form of rickets resulting from disruption of VITAMIN D; PHOSPHORUS; or CALCIUM homeostasis.
Muscle weakness or paralysis of neurologic origin.
Vasculitis, autoinflammation, immunodeficiency, and hematologic defects syndrome (VAIHS) is an autosomal recessive multisystem disorder with onset in childhood. The phenotype is highly variable, but most patients have features of a systemic vascular inflammatory disorder with skin ulceration and recurrent strokes affecting the small vessels of the brain resulting in neurologic dysfunction. Other features may include recurrent fever, elevated acute-phase proteins, myalgias, lesions resembling polyarteritis nodosa, and/or livedo racemosa or reticularis with an inflammatory vasculitis on biopsy. Some patients may have renal and/or gastrointestinal involvement, hypertension, aneurysms, or ischemic necrosis of the digits (summary by Zhou et al., 2014 and Navon Elkan et al., 2014). Some patients present with clinical immunodeficiency (van Eyck et al., 2014). Lee (2018) reviewed the basic biology of ADA2 and the various clinical manifestations of ADA2 deficiency, which include vasculitis affecting small- and medium-sized vessels causing early-onset stroke with subsequent neurologic signs, skin ulcerations resembling polyarteritis nodosa, peripheral neuropathy, immunodeficiency, autoimmune features, and hematologic abnormalities, including anemia and leukopenia. The clinical features are highly pleiotropic, and patients can present with only some of these main features. The hematologic manifestations of the disorder may sometimes resemble Diamond-Blackfan anemia (see, e.g., DBA1, 105650).
Pulmonary venoocclusive disease primarily affects the postcapillary venous pulmonary vessels and may involve significant pulmonary capillary dilation and/or proliferation. PVOD is an uncommon cause of pulmonary artery hypertension (PPH; see 178600), a severe condition characterized by elevated pulmonary artery pressure leading to right heart failure and death. PVOD accounts for 5 to 10% of 'idiopathic' PPH and has an estimated incidence of 0.1 to 0.2 cases per million. The pathologic hallmark of PVOD is the extensive and diffuse occlusion of pulmonary veins by fibrous tissue, with intimal thickening present in venules and small veins in lobular septa and, rarely, larger veins. Definitive diagnosis of PVOD requires histologic analysis of a lung sample, although surgical lung biopsy is often too invasive for these frail patients. Patients with PVOD respond poorly to available therapy, therefore it is crucial to distinguish PVOD from other forms of PPH. Radiologic characteristics suggestive of PVOD on high-resolution CT of the chest include nodular ground-glass opacities, septal lines, and lymph node enlargement. In addition, because PVOD mainly affects postcapillary vasculature, it causes chronic elevation of pulmonary capillary pressure and thus promotes occult alveolar hemorrhage, which may be a characteristic feature of PVOD (summary by Montani et al., 2008). Genetic Heterogeneity of Pulmonary Venoocclusive Disease See also PVOD2 (234810), caused by mutation in the EIF2AK4 gene (609280) on chromosome 15q15.
The sound produced by tissue vibrations in the nasopharynx and pharynx secondary to partial obstruction of the upper airway.
A primary or metastatic neoplasm that occurs within the spinal canal including the spinal cord and surrounding paraspinal spaces.
An electrocardiographic finding of a regular supraventricular tachycardia due to reentry within the AV node. It is characterized by P waves which typically occur nearly simultaneously with the QRS complex, resulting in a P wave which is obscured by the QRS, merged with the QRS or which may follow the QRS. (CDISC)
A form of torticollis in which the head is drawn back, either due to a permanent contractures of neck extensor muscles, or to a spasmodic contracture.
A granuloma caused by infectious organisms and characterized by the presence of abscess formation.
A primitive neuroectodermal neoplasm that occurs in the central nervous system.
Glare can be defined as the contrast lowering effect of stray light in a visual scene.
A recombinant 26.0 kDa protein, containing 227 amino acid residues, a member of the cytokine family and growth and differentiation factor that participates in the regulation of neurogenesis, osteogenesis and hematopoiesis. Produced by activated T cells, monocytes and Kaposi's sarcoma cells, oncostatin M (OSM) can exert both stimulatory and inhibitory effects on cell proliferation. It stimulates the proliferation of fibroblasts, smooth muscle cells and Kaposi's sarcoma cells, but inhibits the growth of some normal and tumor cell lines. It also promotes cytokine release (e.g. IL-6, GM-CSF and G-CSF) from endothelial cells, and enhances the expression of low-density lipoprotein receptor in hepatoma cells.
A humanized, non-Fc receptor (FcR)-binding IgG2 monoclonal antibody (MoAb) directed against CD3 with potential immunosuppressive activity. Visilizumab binds to invariant CD3 epsilon, one of the non-covalently-associated subunits of T-cell receptors (TCRs) on activated T-cells. Upon binding to the TCR/CD3 complex, visilizumab induces apoptosis, which may result in the selective clonal deletion of activated pathogenic T-cells. This MoAb is engineered with a substitution at amino acid residues 234 and 237 (Val3Ala) within the IgG2 Fc arm, rendering it unable to bind to type II FcRs; accordingly, this agent is less likely to activate type II FcR-expressing resting T-cells.
A finding indicating the presence of morphologic features of neoplasia in the epithelium of any part of the digestive system without evidence of invasion. These features include architectural and cytological epithelial alterations.
Projection of the tip of the dens more than 5 mm above a line joining the hard palate to the posterior lip of the foramen magnum (Chamberlain's line) or the tip of the dens is greater than 7 mm above McGregor's line (the back of the hard palate to the lowest point of the occipital squama).
A partial or complete loss of hearing in one or both ears. It is classified as conductive, sensory, or central.
An absolute or relative reduction in the extent of the normal field of vision.
Osteoarthritis (OA) is a degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis (Meulenbelt et al., 2006). Clinical problems include pain and joint stiffness often leading to significant disability and joint replacement. Osteoarthritis exhibits a clear predilection for specific joints; it appears most commonly in the hip and knee joints and lumbar and cervical spine, as well as in the distal interphalangeal and the first carpometacarpal (base of thumb) and proximal interphalangeal joints of the hand; however, patients with osteoarthritis may have 1, a few, or all of these sites affected (Stefansson et al., 2003). According to a conservative estimate, greater than 70% of the population of the United States at age 65 years is affected by the disease, reflecting its age dependence. Genetic Heterogeneity of Susceptibility to Osteoarthritis Susceptibility to osteoarthritis has been associated with variation in other genes: OS2 (140600) with variation in the MATN3 gene (602109) on chromosome 2p24; OS3 (607850) with variation in the ASPN gene (608135) on chromosome 9q22; and OS5 (612400) with variation in the GDF5 gene (601146) on chromosome 20q11. Other susceptibility loci for osteoarthritis have been mapped to chromosomes 2q33 (OS4; 610839) and 3p24 (OS6; 612401).
Bicuspid, or bicommissural, aortic valve (BAV) describes an aortic valve with 2 rather than 3 leaflets (Cripe et al., 2004). In 1 to 2% of the population a bicuspid aortic valve is present. Bicuspid aortic valve is frequently an antecedent to aortic valve stenosis or insufficiency. In extreme cases the blood flow may be so restricted that the left ventricle fails to grow, resulting in hypoplastic left heart syndrome (241550) (Garg et al., 2005). The valve calcification often observed in bicuspid aortic valve is a result of inappropriate activation of osteoblast-specific gene expression. Mutations in the signaling and transcription regulator NOTCH1 cause a spectrum of developmental aortic valve anomalies and severe valve calcification in nonsyndromic autosomal dominant human pedigrees. Genetic Heterogeneity of Aortic Valve Disease Aortic valve disease-2 (AOVD2; 614823) is caused by mutation in the SMAD6 gene (602931) on chromosome 15q22. There is evidence for additional genetic heterogeneity (see MAPPING).
A hormonal disorder that occurs when the adrenal glands fail to release adequate amounts of glucocorticoids (cortisol), mineralocorticoids (aldosterone, 11-deoxycorticosterone), and androgens (dehydroepiandrosterone) to meet physiologic needs, despite release of ACTH from the pituitary.
Infantile spasms represent a subset of ""epileptic spasms"". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
A carcinoma that does not respond to treatment.
A type of anomalous trichromacy associated with abnormal M photopigment, such that the absorption spectrum is shifted toward L wavelengths. Affected individuals have difficulties distinguishing between red and green. [HPO:probinson]
Apparent mineralocorticoid excess (AME) is an autosomal recessive form of low-renin hypertension associated with low aldosterone, metabolic alkalosis, hypernatremia, and hypokalemia. The disorder is due to a congenital defect in 11-beta-hydroxysteroid dehydrogenase type II (HSD11B2) activity, resulting in decreased conversion of biologically active cortisol to inactive cortisone; this defect allows cortisol to act as a ligand for the mineralocorticoid receptor, resulting in sodium retention and volume expansion. There is a favorable therapeutic response to spironolactone (review by Ferrari, 2010).
Raynaud-Claes syndrome is an X-linked intellectual developmental disorder characterized by borderline to severe intellectual disability and impaired language development. Additional features include behavioral problems, psychiatric disorders, seizures (variable forms), progressive ataxia, brain abnormalities, and facial dysmorphisms. Some heterozygous females are unaffected, whereas others are affected with a severity spectrum similar to that seen in males (summary by Palmer et al. (2018)).
A type of anomalous trichromacy associated with defective long-wavelength-sensitive (L) cones, causing the sensitivity spectrum to be shifted toward medium wavelengths. This leads to difficulties especially in distinguishing red and green. [HPO:probinson]
Body mass index (BMI), which reflects the amount of fat, lean mass, and body build, is a heterogeneous trait influenced by both genetic and environmental factors. Several studies have estimated the heritability of body mass index to be 40 to 55% (Bouchard et al., 1998; Rice et al., 1999). For discussion of genetic heterogeneity of BMI quantitative trait loci and their known or possible associations with variation in specific genes, see MAPPING and MOLECULAR GENETICS sections.
Fibrosis of the skin, joints and other organs usually associated with gadolinium exposure in the setting of kidney failure.
Y-linked deafness-1 (DFNY1) is characterized by male-limited postlingual progressive sensorineural hearing loss of variable severity, with onset in the first to third decades of life (Wang et al., 2009). Genetic Heterogeneity of Y-Linked Deafness DFNY2 (400047) is caused by mutation in the TBL1Y gene (400033).
An orally bioavailable inhibitor of the epidermal growth factor receptor family with potential antineoplastic activity. Varlitinib selectively and reversibly binds to both EGFR (ErbB-1) and Her-2/neu (ErbB-2) and prevents their phosphorylation and activation, which may result in inhibition of the associated signal transduction pathways, inhibition of cellular proliferation and cell death. EGFR and Her-2 play important roles in cell proliferation and differentiation and are upregulated in various human tumor cell types. Due to the dual inhibition of both EGFR and Her-2, this agent may be therapeutically more effective than agents that inhibit EGFR or Her-2 alone.
Smith-McCort dysplasia is a rare autosomal recessive osteochondrodysplasia characterized by short limbs and trunk with barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest, features identical to those of Dyggve-Melchior-Clausen disease. Spinal cord compression due to atlantoaxial instability occurs in both SMC and DMC (Spranger et al., 1976; Nakamura et al., 1997). Genetic Heterogeneity of Smith-McCort Dysplasia Smith-McCort dysplasia-2 (SMC2; 615222) is caused by mutation in the RAB33B gene (605950) on chromosome 4q31.
A genetic disorder that usually presents in early childhood and is characterized by muscle contractions in a foot, leg, or arm that gradually spreads to other body regions.
Mutations in the MAF gene have been found to cause multiple types of cataract, which have been described as cortical pulverulent, lamellar, nuclear, nuclear pulverulent, nuclear stellate, anterior polar, anterior subcapsular, posterior subcapsular, and cerulean. In some cases, the cataracts are of juvenile onset. The preferred title of this entry was formerly 'Cataract, Pulverulent, Juvenile-Onset,' with an 'Included' title/symbol of 'Cataract, Congenital, Cerulean Type, 4; CCA4.'
Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a disorder that affects several parts of the eyes, including the clear gel that fills the eye (the vitreous), the light-sensitive tissue that lines the back of the eye (the retina), and the network of blood vessels within the retina (the choroid). The eye abnormalities in ADVIRC can lead to varying degrees of vision impairment, from mild reduction to complete loss, although some people with the condition have normal vision.The signs and symptoms of ADVIRC vary, even among members of the same family. Many affected individuals have microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved. The area behind the cornea can also be abnormally small, which is described as a shallow anterior chamber. Individuals with ADVIRC can develop increased pressure in the eyes (glaucoma) or clouding of the lens of the eye (cataract). In addition, some people have breakdown (degeneration) of the vitreous or the choroid.A characteristic feature of ADVIRC, visible with a special eye exam, is a circular band of excess coloring (hyperpigmentation) in the retina. This feature can help physicians diagnose the disorder. Affected individuals may also have white spots on the retina.
Frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) is an autosomal dominant neurodegenerative disorder characterized by adult onset of one or both of these features in an affected individual, with significant intrafamilial variation. The disorder is genetically and pathologically heterogeneous (summary by Vance et al., 2006). Patients with C9ORF72 repeat expansions tend to show a lower age of onset, shorter survival, bulbar symptom onset, increased incidence of neurodegenerative disease in relatives, and a propensity toward psychosis or hallucinations compared to patients with other forms of ALS and/or FTD (summary by Harms et al., 2013). Patients with C9ORF72 repeat expansions also show psychiatric disturbances that may predate the onset of dementia (Meisler et al., 2013; Gomez-Tortosa et al., 2013). For a general phenotypic description of frontotemporal dementia, also known as frontotemporal lobar degeneration (FTLD), see 600274. For a general discussion of motor neuron disease (MND), see amyotrophic lateral sclerosis-1 (ALS1; 105400). Genetic Heterogeneity of Frontotemporal Dementia and/or Amyotrophic Lateral Sclerosis See also FTDALS2 (615911), caused by mutation in the CHCHD10 gene (615903) on chromosome 22q11; FTDALS3 (616437), caused by mutation in the SQSTM1 gene (601530) on chromosome 5q35; and FTDALS4 (616439), caused by mutation in the TBK1 gene (604834) on chromosome 12q14.
Autosomal dominant deafness-50 is a form of nonsyndromic hearing loss. Hearing impairment shows postlingual onset and is progressive (summary by Mencia et al., 2009).
Mutations in the CRYBB1 gene have been found to cause multiple types of cataract, which have been described as congenital nuclear, congenital nuclear with anterior and posterior Y-suture and polar opacities, and pulverulent. The preferred title/symbol for this entry was formerly 'Cataract, Congenital Nuclear, Autosomal Recessive 3; CATCN3.'
A retinal dystrophy with characteristics of central visual loss in the first 2 decades of life, associated with an absent electrooculogram (EOG) light rise and a reduced electroretinogram (ERG). To date less than 20 cases have been described in the world literature. Caused by compound heterozygous or homozygous mutations in the BEST1 gene (11q12) which encodes the chloride ion channel bestrophin-1 (expressed in the retinal pigment epithelium (RPE)). Mutations in BEST1 reduce or abolish the activity of the channel. It has been proposed that ARB may represent the null phenotype of bestrophin-1 in humans. Transmission is autosomal recessive.
Approximately 16% of the world population is predicted to have congenital deficiency of alpha-actinin-3 based on a common nonsense polymorphism in the ACTN3 gene. Expression of alpha-actinin-3 is limited to a subset of type 2 (fast) fibers. No disease phenotype is associated with this deficiency (North et al., 1999).
Recurrent gastrointestinal ulceration with dysfunctional platelets (GURDP) is an autosomal recessive disorder characterized by onset of severe gastrointestinal mucosal ulceration in early childhood. Affected individuals may have secondary iron deficiency anemia or malnourishment. Studies of platelet aggregation show a functional defect associated with decreased thromboxane-A2 production and decreased eicosanoid biosynthesis. The gastrointestinal disease is believed to result from decreased or absent production of prostaglandins that protect the gut mucosa (summary by Adler et al., 2008 and Faioni et al., 2014).
Seckel syndrome is a rare autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, severe microcephaly with mental retardation, and specific dysmorphic features (Faivre et al., 2002). For a general description and a discussion of genetic heterogeneity of Seckel syndrome, see 210600.
Distal hereditary motor neuronopathy type IID is an autosomal dominant neurologic disorder characterized by onset of slowly progressive distal lower limb weakness and atrophy between the second and fourth decades of life. Weakness usually begins in the calf muscles and later involves more proximal muscles. The severity is variable, and some patients have difficulty walking or running. Most also have upper limb involvement, particularly of the triceps and intrinsic hand muscles. Some patients may lose independent ambulation later in the disease course. Sensory impairment is typically not present, and cognition and bulbar function are normal (summary by Sumner et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN (dHMN), see HMN type I (HMN1; 182960).
Autosomal recessive deafness-96 (DFNB96) is a form of nonsyndromic sensorineural severe to profound hearing impairment with prelingual onset (summary by Ansar et al., 2011).
Glaucomas are a group of common neurodegenerative diseases of the optic nerve and retinal ganglion cells, characterized by progressive cupping of the optic nerve head with resultant visual field loss. Elevated intraocular pressure (IOP) is a strong risk factor for glaucoma; however, glaucoma can occur at any IOP. The most common form of glaucoma in the US is primary open-angle glaucoma (POAG; see 137760). POAG that occurs with an IOP below an arbitrary threshold of 21 mm Hg is often termed 'normal tension glaucoma' (summary by Fingert et al., 2011). For a discussion of genetic heterogeneity of primary open angle glaucoma, see 137760.
Otosclerosis is a hearing disorder that is associated with disordered bone remodeling in the otic capsule. The bone remodeling can result in conductive, mixed, or sensorineural hearing loss as a result of stapes footplate fixation or cochlear involvement (summary by Schrauwen et al., 2011).
Autosomal recessive deafness-93 is characterized by moderate to severe prelingual deafness and a distinctive U-shaped audiogram (Tabatabaiefar et al., 2011).
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group 8 (CG8, equivalent to CGA) have mutations in the PEX26 gene. For information on the history of PBD complementation groups, see 214100.
Oculocutaneous albinism is a genetically heterogeneous disorder manifested as a loss of pigmentation in the eyes, skin, and hair (summary by Kausar et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of oculocutaneous albinism, see OCA1 (203100).
Congenital cataracts cause 10 to 30% of all blindness in children, with one-third of cases estimated to have a genetic cause (summary by Bu et al., 2002). Mutations in the HSF4 gene have been found to cause multiple types of cataract, which have been described as infantile, lamellar, zonular, nuclear, anterior polar, stellate, and Marner-type. The preferred title for this entry was formerly 'Lamellar Cataract,' with 'Cataract, Marner Type; CAM; CTM' an included title.
A circumscribed inflammatory lesion associated with underlying ischemic disease.
Obstruction of the bowel by an advanced malignant tumor. It is a complication especially in patients with an advanced abdominal malignant tumor.
Diabetes mellitus caused by mutation(s) in a single gene, usually presenting in childhood or early adulthood.
Glycogen storage disease (GSD) due to acid maltase deficiency, classical infantile onset (AMDI), is the most severe form of glycogen storage disease due to acid maltase deficiency. Characterised by cardiomegaly with respiratory distress, muscle weakness and feeding difficulties, it is potentially fatal.
Glycogen storage disease due to acid maltase deficiency, late onset (AMDL), a form of Glycogen storage disease due to acid maltase deficiency (AMD), a degenerative metabolic myopathy particularly affecting respiratory and skeletal muscles, is characterized by an accumulation of glycogen in lysosomes.
A form of spondyloarthritis in which the predominant symptom is back pain, and where radiographic sacroiliitis might or might not be present.
A response indicating that something occurs with little frequency or intensity.
An autoinflammatory disease caused by mutations in the TNFRSF1A gene coding for tumor necrosis factor receptor 1 (TNFR1). This results in attacks of fever, rash, peritoneal, pleural, or pericardial serositis and/or synovial inflammation along with increased acute phase reactants. Complications may include amyloidosis.
Severe - symptoms or pathological characteristics include somnolence with some arousability, inability to perform mental tasks, disorientation about time and place, marked confusion, amnesia, occasional fits of rage, present but incomprehensible speech. (Adapted from: Hepatic Encephalopathy. David C Wolf. http://emedicine.medscape.com/article/186101-overview.)
Mild - symptoms or pathological characteristics include trivial lack of awareness, shortened attention span, impaired ability to perform addition or subtraction, hypersomnia, insomnia, or inversion of sleep pattern, euphoria, depression or irritability, mild confusion, slowing of ability to perform mental tasks. (Adapted from: Hepatic Encephalopathy. David C Wolf. http://emedicine.medscape.com/article/186101-overview.)
A group of genetically-determined conditions characterized by a wide spectrum of seizure types occurring in otherwise healthy newborn infants that start during the first week of life and spontaneously disappear between the first and twelfth months of life.
Spinocerebellar ataxia-37 (SCA37) is an autosomal dominant neurologic disorder characterized by adult onset of slowly progressive gait instability, frequent falls, and dysarthria associated with cerebellar atrophy on brain imaging (summary by Seixas et al., 2017). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Focally amplified long non-coding RNA in epithelial cancer (566 bp) is encoded by the human FALEC gene. This non-coding RNA may be involved in oncogenesis.
An orally bioavailable procaspase activating compound-1 (PAC-1), with potential proapoptotic and antineoplastic activities. Upon administration, VO-100 binds to and forms a chelating complex with zinc (Zn) ions inside cells, which prevents the binding of Zn ions to procaspase-3 (PC3) and abrogates the Zn-mediated inhibition of PC3. This allows for the proteolytic autoactivation of PC3 into the active form caspase-3. This results in the selective caspase-3-mediated induction of apoptosis and cell death in cancer cells. In addition, VO-100 is able to cross the blood-brain-barrier (BBB). PC3, a Zn-inhibited proenzyme, is upregulated in a variety of cancer cell types, while its expression is minimal in normal healthy cells.
Fevers of unknown etiology recurring over months or years.
A category of juvenile idiopathic arthritis defined by the presence of arthritis with a personal or family history of psoriasis, and features such as dactylitis and nail dystrophy.
A category of juvenile idiopathic arthritis defined by the presence of arthritis affecting five or more separate joints during the first six months of disease, with negative serologic testing for rheumatoid factor.
Minimal - symptoms or pathological characteristics include minimal hepatic encephalopathy, lack of detectable changes in personality or behavior, minimal changes in memory, concentration and intellectual function, and absence of coordination asterixis. (Adapted from: Hepatic Encephalopathy. David C Wolf. http://emedicine.medscape.com/article/186101-overview)
An orally bioavailable, traditional Chinese medicine (TCM)-based formulation composed of Realgar-Indigo naturalis formula (RIF) with potential antineoplastic activity. The main constituents in RIF are realgar, Indigo naturalis, and Salvia miltiorrhiza, with tetraarsenic tetrasulfide (As4S4), indirubin and tanshinone IIA as the main active ingredients, respectively, which appear to exert synergistic effects on cancer cells. Tetraarsenic tetrasulfide specifically induces the ubiquitination and degradation of promyelocytic leukemia retinoic acid receptor alpha (PML-RARalpha) oncoprotein. In addition, the active ingredients in the Realgar-Indigo naturalis formulation enhance the expression of myeloid differentiation genes, and induce G(1)/G(0) cell cycle arrest. PML-RARalpha, an acute promyelocytic leukemia (APL)-specific fusion gene, inhibits differentiation and promotes survival of myeloid precursor cells
A constellation of symptoms lasting months to years reported by some Lyme disease patients who had undergone previous antibiotic therapy.
A malignant tumor that originates from myeloid or lymphoid cells i.e., leukemias and lymphomas.
An electrocardiographic finding showing no cardiac electrical activity on the monitor or printed strip for the entire duration of the recording. (CDISC)
A traditional Chinese medicine (TCM) formulation composed of compound Kushen injection (CKI) containing aqueous extracts from the roots of Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma smilacis Glabrae), with potential antineoplastic and immunomodulating activities. CKI contains numerous chemicals including alkaloids, such as matrine and oxymatrine, flavonoids, alkylxanthones, quinones, triterpene glycosides, fatty acids, and essential oils. Although the exact mechanism(s) of action through which CKI exerts its effects has yet to be fully elucidated, CKI is able to interfere with the activation of various signal transduction pathways, such as the Wnt/beta-catenin signaling pathway, inhibit nuclear factor-kappa B (NF-KB) activation, and block the activity of multiple receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR). CKI induces apoptosis in and inhibits proliferation, migration, invasion and adhesion of tumor cells. CKI also modulates the production of inflammatory mediators.
An ultrastructural finding in adipose tissue that indicates macrophage infiltration to sites of adipocyte necrosis.
The sensation of acute or chronic suffering in a body region.
An electrocardiographic recording that demonstrates an R-R interval that exceeds a predefined duration threshold, irrespective of the underlying rhythm.
A category of juvenile idiopathic arthritis defined by the presence of arthritis affecting five or more separate joints during the first six months of disease, with positive serologic testing for rheumatoid factor.
The disappearance of all signs of cancer in response to treatment, accompanied by incomplete platelet recovery (platelet count is less than 100,000/uL).
A group of disorders of the innate immune system characterized by attacks of seemingly unprovoked inflammation without significant levels of either autoantibodies or autoreactive T cells more characteristic of autoimmune disease.
A pure motor axonal form of Guillain-Barré syndrome that presents with rapid onset of muscle weakness and absent reflexes. The clinical course tends to be more severe than in the more frequent, demyelinating form of Guillain-Barré syndrome. In the majority of cases, this disease occurs following Campylobacter jejuni infection, in particular following infection with strains of C jejuni that cause enteritis.
A proprietary lipid emulsion containing five vaccines: diphtheria, pertussis, tetanus (DPT), Bacille Calmette-Guerin (BCG), measles, Serratia marcescens and pneumococcal, with potential immunostimulating activity. Subcutaneous administration of the DPT/BCG/measles/Serratia/pneumococcus vaccine activates the immune system and may both abrogate tumor-induced immune tolerance and induce an antitumor immune response, which may eradicate the tumor.
An electrocardiographic finding of an escape beat following a pause that originates at the AV junction; this manifests as a QRS complex of supraventricular origin not immediately preceded by a P wave. (CDISC)
A traditional Chinese medicine (TCM) derived from the plant Gynostemma pentaphyllum, an herbaceous climbing vine found in southern China and Southeast Asia, with potential antioxidant activity. Gynostemma pentaphyllum intake has also been used for its adaptogenic effect, to decrease cholesterol and high blood pressure, to strengthen the immune system, and to increase stamina and to improve memory.
A synthetic form of a human antimicrobial peptide (37 amino acids), belonging to the cathelicidin family, with antimicrobial, anti-inflammatory, immunostimulating and potential antineoplastic activities. Upon intratumoral injection of the cathelicidin LL-37, this peptide increases p53 expression, and induces phosphatidylserine externalization, DNA fragmentation, cell cycle arrest and caspase-independent apoptosis-inducing factor (AIF)/ endonuclease G (EndoG)-mediated apoptotic cell death in susceptible cancer cells. This suppresses tumor cell proliferation. LL-37, a protein secreted by bone marrow cells, circulating leukocytes, and various epithelial tissues, plays a crucial role in the innate host immune defense via the regulation of leukocyte chemotaxis and cytokine production; it also promotes wound healing.
A well differentiated neuroendocrine tumor (carcinoid tumor) that arises from the digestive system and has spread to other anatomic sites.
Neural tube defects are the second most common type of birth defect after congenital heart defects. The 2 most common NTDs are open spina bifida, also known as spina bifida cystica (SBC) or myelomeningocele, and anencephaly (206500) (Detrait et al., 2005). Spina bifida occulta (SBO), a bony defect of the spine covered by normal skin, is a mild form of spina bifida that is often asymptomatic. The term 'spinal dysraphia' refers to both SBC and SBO (Botto et al., 1999; Fineman et al., 1982). The most severe neural tube defect, craniorachischisis (CRN), leaves the neural tube open from the midbrain or rostral hindbrain to the base of the spine (summary by Robinson et al., 2012). Neural tube defects represent a complex trait with multifactorial etiology encompassing both genetic and environmental components (summary by Bartsch et al., 2012 and Lei et al., 2014). An X-linked form of spina bifida has been suggested; see 301410. See also folate-sensitive neural tube defects (601634), which are caused by genes involved in folate metabolism.
Seckel syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (summary by Shanske et al., 1997). For a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600).
An orally available Lactobacillis casei (L. casei)-based vaccine expressing the human papillomavirus (HPV) type 16 isoform E7 protein linked to the poly-gamma-glutamate synthetase complex gene pgsA, with potential immunostimulating activity. Upon oral administration, the expressed HPV 16 E7 may stimulate the immune system to mount a mucosal cytotoxic T-lymphocyte (CTL) response against HPV 16 E7-expressing tumor cells. The poly-glutamic acid synthetase PgsA from Bacillus subtilis acts as an anchoring motif that facilitates the expression of the HPV antigen protein on the surface of the bacteria. HPV 16 E7, a cell surface glycoprotein and tumor associated antigen, is overexpressed in various viral-related cancers.
X-linked acrogigantism is the occurrence of pituitary gigantism in an individual heterozygous or hemizygous for a germline or somatic duplication of GPR101. X-linked acrogigantism is characterized by acceleration of linear growth in early childhood – in most cases during the first two years of life – due to growth hormone (GH) excess. Most individuals with X-linked acrogigantism present with associated hyperprolactinemia due to a mixed GH- and prolactin-secreting pituitary adenoma with or without associated hyperplasia; less commonly they develop diffuse hyperplasia of the GH- and prolactin-secreting pituitary cells without a pituitary adenoma. Most affected individuals are females. Growth acceleration is the main presenting feature; other frequently observed clinical features include enlargement of hands and feet, coarsening of the facial features, and increased appetite. Neurologic signs or symptoms are rarely present. Untreated X-linked acrogigantism can lead to markedly increased stature, with obvious severe physical and psychological sequelae.
A condition characterized by the presence of a growing mature teratoma in a patient during or after chemotherapy for a non-seminomatous germ cell tumor, with normal serum markers for human chorionic gonadotropin and alpha fetoprotein. Complete surgical resection is the preferred treatment.
A multiple electrolyte, isotonic, crystalloid solution for intravenous infusion containing sodium chloride, potassium chloride, calcium chloride dihydrate, and sodium lactate, which can restore the electrolyte balance, normalize pH, and provide water for hydration. Upon intravenous administration, the compound sodium lactate solution will replace any lost body fluids and electrolytes thereby providing hydration as well as normalizing electrolyte concentrations. In addition, conversion of sodium lactate to bicarbonate increases plasma bicarbonate levels, which facilitates the removal of hydrogen ions from the blood stream, raises blood pH and normalizes the acid-base balance.
A response indicating that an individual has or had no pain.
Acute inflammation of one or more joints caused by the presence of pus within the joint cavity.
Permanent neonatal diabetes mellitus is a type of diabetes that first appears within the first 6 months of life and persists throughout the lifespan. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy.Individuals with permanent neonatal diabetes mellitus experience slow growth before birth (intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration) and are unable to gain weight and grow at the expected rate (failure to thrive).In some cases, people with permanent neonatal diabetes mellitus also have certain neurological problems, including developmental delay and recurrent seizures (epilepsy). This combination of developmental delay, epilepsy, and neonatal diabetes is called DEND syndrome. Intermediate DEND syndrome is a similar combination but with milder developmental delay and without epilepsy.A small number of individuals with permanent neonatal diabetes mellitus have an underdeveloped pancreas. Because the pancreas produces digestive enzymes as well as secreting insulin and other hormones, affected individuals experience digestive problems such as fatty stools and an inability to absorb fat-soluble vitamins.
An orally bioavailable, glucoside derivative of the flavonoid quercetin and protein disulfide isomerase (PDI) inhibitor, with antioxidant and potential antithrombotic activity. As an antioxidant, isoquercetin scavenges free radicals and inhibits oxidative damage to cells. As a PDI inhibitor, this agent blocks PDI-mediated platelet activation, and fibrin generation, which prevents thrombus formation after vascular injury. In addition, isoquercetin is an alpha-glucosidase inhibitor. PDI, an oxidoreductase secreted by activated endothelial cells and platelets, plays a key role in the initiation of the coagulation cascade. Cancer, in addition to other thrombotic disorders, increases the risk of thrombus formation.
A formulation for intravenous injection containing ibuprofen, a propionic acid derivate and nonsteroidal anti-inflammatory drug (NSAID), with anti-inflammatory, analgesic, and antipyretic activities. Upon intravenous injection, ibuprofen inhibits the activity of the enzymes cyclooxygenase I (COX-1) and II (COX-2), resulting in a decreased formation of precursors of prostaglandins and thromboxanes. Inhibition of COX-2 specifically blocks the conversion of arachidonic acid (AA) to prostaglandins, which mediate inflammation, fever and pain.
An arthritis affecting fewer than five separate joints.
A malignant neoplasm of the central nervous system arising from oligodendrocytes.
A biosimilar of filgrastim, a recombinant form of the endogenous cytokine human granulocyte colony-stimulating factor (G-CSF), with hematopoietic activity. Filgrastim-sndz specifically binds to and activates G-CSF receptors with the same biological activity and stability as the endogenous cytokine, thereby controlling the production, differentiation, and function of neutrophilic granulocyte progenitors. This may decrease the duration and prevent the incidence of chemotherapy-induced neutropenia (CIN).
Hereditary nonpolyposis colorectal cancer characterized by the absence of germline mutations in DNA mismatch-repair genes.
Autologous human lymph node T-lymphocytes, with potential immunostimulatory and antineoplastic activity. Upon collection of immune cells from the tumor-draining lymph node, the human lymph node lymphocytes are activated with anti-CD3/anti-CD28 microbeads, cultured with recombinant, human interleukin-2 (IL-2), expanded and isolated ex vivo. Upon reintroduction into the patient, the ex vivo-activated autologous lymph node lymphocytes recognize and lyse the tumor cells.
A nutritional supplement composed of serum-derived bovine protein concentrate containing high levels of immunoglobulins (Ig), particularly IgG, with the potential to improve nutritional status. Upon oral administration of SBI, the Ig promotes gastrointestinal (GI) health by improving the composition of the GI microflora, enhancing digestive processes, and increasing gut barrier integrity and function. SBI may also improve immune function, maintain immune homeostasis, bind to and neutralize bacterial toxins and antigens, and decrease intestinal inflammation. Altogether, this may enhance the functioning of the GI tract, improve both the digestion and absorption of nutrients, and increase weight gain.
Bleeding into the brain tissue adjacent to the lateral cerebral ventricles of newborn infant.
A radiopharmaceutical comprised of oxygen-15 labeled oxygen (15O-O2) used as a tracer molecule during positron emission tomography (PET). Upon inhalation, 15O-O2 binds to hemoglobin in the blood and the labeled red blood cells distribute throughout the vasculature in the body. Upon PET imaging, 15O-O2 can be used to determine both the oxygen extraction fraction (OEF) and the metabolic rate of oxygen.
Development of diabetes after transplant, usually associated with calcineurin inhibitor use.
A cancer vaccine composed of a replication-deficient, attenuated derivative of the vaccinia virus strain Ankara expressing both a CD8+ T-cell epitope from the brachyury protein and a triad of T-cell co-stimulatory molecules (MVA Brachyury-TRICOM), with potential immunomodulating and antineoplastic activities. Upon subcutaneous administration of the brachyury-expressing modified vaccinia Ankara (MVA)-TRICOM vaccine, the expressed brachyury protein induces specific CD8+ and CD4+ T-cell responses against brachyury-expressing tumor cells. This causes both tumor cell lysis and a decrease in the growth of brachyury-expressing tumor cells. Brachyury, a member of the T-box family of transcription factors that is overexpressed in numerous cancer cell types, is correlated with increased epithelial-mesenchymal transition (EMT), cancer resistance and cancer progression. TRICOM, a triad of three human T-cell co-stimulatory molecules, B7.1, ICAM-1 and LFA-3, enhances antigen-specific T-cell activation.
An oral rinse containing miracle mouthwash and the corticosteroid hydrocortisone, with potential anti-mucositic activity. Upon rinsing with this mouthwash, the ingredients in the miracle mouthwash may provide analgesia; the hydrocortisone modulates the production of pro-inflammatory cytokines which may prevent inflammation of the oral mucosa, and reduce chemotherapy- and/or radiation-induced oral mucositis.
A vaccine consisting of the attenuated, genetically-modified, oncolytic form of the Maraba virus, MG1, which has been engineered to express a gene encoding the cancer testis antigen melanoma antigen family A3 (MAGE-A3), with potential antineoplastic activity. Upon administration of genetically-modified MAGE-A3-expressing MG1 Maraba virus vaccine, the attenuated Maraba virus selectively and rapidly replicates in cancer cells; however, it is unable to replicate in normal, healthy cells. This induces a selective Maraba virus-mediated cytotoxicity in those cancer cells, and leads to cancer cell lysis. In addition, the expression of MAGE-A3 further stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing MAGE-A3. The tumor-associated antigen MAGE-A3 is overexpressed by a variety of cancer cell types. The attenuated virus is a double mutant strain with single amino acid substitutions occurring in both G protein (Q242R) and M protein (L123W).
A peptide vaccine consisting of a combination of seven synthetic long peptides (SLPs), which are each about 30 amino acids in size, and derived from cancer-testis antigens (CTA) and melanocytic differentiation proteins (MDP), with potential immunostimulating and antitumor activities. Upon administration, long peptide vaccine 7 may stimulate the host immune system to mount a cytotoxic T-cell lymphocyte (CTL) response against tumor cells expressing these peptides. CTA and MDP are overexpressed in a variety of cancer cell types.
A depot suspension for injection composed of the mesylate salt of leuprolide, a synthetic, long-acting nonapeptide analog of the endogenous hormone gonadotropin-releasing hormone (GnRH), with potential antineoplastic activity. Upon subcutaneous injection of the depot suspension, leuprolide binds to and activates the gonadotropin-releasing hormone receptor (GnRHR). The continuous stimulation of GnRHR by leuprolide results in both the desensitization of pituitary GnRHR and the inhibition of pituitary secretion of the gonadotropins follicle stimulating hormone (FSH) and luteinizing hormone (LH). In males, this results in a significant decline in testosterone production to castration levels and may inhibit androgen receptor-positive tumor progression.
An orally bioavailable, blood brain barrier (BBB) penetrating, chlorinated analog of the endogenous neuromodulator kynurenic acid and prodrug of 7-chlorokynurenic acid (7-Cl-KYNA), a N-methyl-D-aspartate receptor (NMDA-R) antagonist at the glycine-coagonist (GlyB) site, with potential anti-hyperalgesic, neuroprotective and anti-epileptic activities. Unlike 7-Cl-KYNA, L-4-chlorokynurenine, upon oral administration, crosses the BBB and is enzymatically converted, through transamination, within activated astrocytes located at sites of injury in the central nervous system (CNS) to its active metabolite, 7-Cl-KYNA, which allows for high levels of this active metabolite at these specific sites. In turn, 7-Cl-KYNA selectively binds to and blocks the GlyB site within the NMDA receptors. This inhibits both NMDA-R overstimulation by the excitatory neurotransmitter glutamate and NMDA-R-mediated excitotoxicity, which prevents neuronal damage and induces analgesia. In addition, another metabolite, 4-chloro-3-hydroxyanthranilic acid, inhibits the synthesis of quinolinic acid, an endogenous NMDA receptor agonist, thereby further preventing excitotoxic damage. Compared to conventional NMDA-R antagonists, NMDA-R GlyB-specific antagonists appear to have fewer side effects.
Chronic, diffuse, non-inflammatory musculoskeletal pain disorder associated with fatigue and sleep disturbance that can occur in childhood and adolescence. Tender points are not necessary to make the diagnosis, but if present may be less numerous than found in adults.
A sterile, absorbable surgical sealing patch composed of an equine collagen sponge coated with the coagulation factors human fibrinogen and human thrombin, with potential hemostatic activity. Applied on the wound tissue, the absorbable fibrin sealant patch adheres to the tissue and the solid fibrinogen and thrombin dissolve upon contact with the physiological fluid. In turn, fibrinogen is converted to fibrin monomers by thrombin, and polymerize to form a fibrin clot at the wound surface. This causes the patch to adhere to the wound surface and promotes tissue sealing. This may reduce lymphatic drainage and prevent seroma formation.
A cell-based vaccine composed of autologous-monocyte-derived dendritic cells (DCs) loaded with five immunogenic peptide epitopes, derived from the tumor-associated antigen human folate receptor alpha (FR alpha or FOLR1), including FR30, FR56, FR76, FR113, and FR238, with potential immunomodulatory and antineoplastic activity. Ex vivo treatment of the DCs with a p38 inhibitor decreases p38-mediated signaling and enhances ERK activation. This may allow, upon intradermal administration of the multi-epitope FR alpha-loaded DC vaccine into the patient, for decreased activation and expansion of CD4+ regulatory T-cells (Tregs), increased differentiation and expansion of interleukin-17 secreting T helper cells (Th17) and activation of CD8+ CTLs, which induces a strong anti-tumor T-cell immune response against FR alpha-overexpressing tumor cells. FR alpha is a high-affinity folate-binding protein and a member of the folate receptor family; this receptor is overexpressed in the majority of ovarian cancers and in about approximately 50% of breast cancers.
A papillary or follicular thyroid gland carcinoma with a genetic component that develops within the same family. Current studies suggest that it is inherited in an autosomal dominant pattern. It is often multifocal and bilateral and usually affects younger patients.
Orally available, nanobubble-based, electrokinetically modified water (EMW) composed of reverse osmosis water where the minerals calcium chloride, magnesium chloride, and potassium bicarbonate have been added and with an increased oxygen concentration compared to normal water. Upon consumption, the EMW may have a beneficial effect on fatigue. This water may protect muscle cells against damage and may improve skeletal muscle function. The water is pretreated with strong, controlled turbulence to create charge-stabilized nanostructures.
A therapeutic melanoma vaccine consisting of autologous dendritic cells (DCs) pulsed with antigens from lethally irradiated autologous tumor cells derived from a patient-specific, continuously proliferating and melanoma-initiating cell line and suspended in a solution containing the cytokine granulocyte-macrophage colony stimulating factor (GM-CSF), with potential immunostimulatory and antineoplastic activities. Upon subcutaneous administration, melapuldencel-T may stimulate the immune system to exert a cytotoxic T-lymphocyte (CTL) immune response against the patient's repertoire of melanoma-associated antigens, particularly tumor stem cell antigens, found in the irradiated autologous cancer cells. As an immunostimulant, GM-CSF enhances the activation of dendritic cells (DCs) and promotes antigen presentation to both B- and T-lymphocytes.
An oncolytic adenoviral vaccine composed of a replication-defective, E1- and E3-deleted adenovirus serotype 5 (Ad5) with a transgene encoding the human melanoma antigen A3 (MAGE-A3), with potential antineoplastic activity. Upon administration, MAGE-A3-expressing adenovirus type 5 vaccine selectively replicates in cancer cells and expresses MAGE-A3. This induces an immune response against tumor cells expressing the MAGE-A3 antigen, which leads to tumor cell death. The tumor-associated antigen MAGE-A3 is overexpressed by a variety of cancer cell types.
A radiolabeled divalent histamine-succinyl-glycine (HSG) hapten-peptide linked with the macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the beta-emitting radionuclide yttrium 90 (Y-90), with radioimmunotherapeutic activity. After pre-treating and targeting tumor cells with a bi-specific monoclonal antibody (BiMoAB) directed against both a tumor-associated antigen (TAA) and the HSG hapten-peptide, the HSG portion of the administered yttrium Y 90-DOTA-di-HSG peptide IMP-288 binds to the anti-HSG sequence on the BiMoAB. In turn, Y-90 delivers a cytotoxic dose of beta radiation to tumor cells expressing the specific TAA.
A proprietary, lung-targeted, site specific immunomodulator (SSI), with potential immunostimulating and antineoplastic activities. Although the exact type and composition of the lung-targeted immunomodulator QBKPN has yet to be fully disclosed, upon subcutaneous administration, this agent is able to activate a local innate immune response in the lung tissue. This results in an increased number of M1 macrophages, which induces a shift from M2 to M1 macrophage dominance in the tumor microenvironment, and stimulates the recruitment of other immune cells. The M1 macrophages exert antitumor activity and eradicate lung cancer cells through phagocytosis. QBKPN does not induce a systemic immune response or affect other organs or tissues. Altogether, this SSI may decrease tumor cell growth in the lungs. SSIs contain specific, inactivated components of pathogens, such as bacteria and/or viruses, which normally cause an acute infection in the specific organ or tissue of interest.
An orally available, aromatically substituted thiazole and inhibitor of the human ribonucleotide reductase (RNR), with potential antineoplastic activity. Upon oral administration, the RNR inhibitor COH29 binds to the ligand-binding pocket of the RNR M2 subunit (hRRM2) near the C-terminal tail. This blocks the interaction between the hRRM1 and hRRM2 subunits and interferes with the assembly of the active hRRM1/hRRM2 complex of RNR. Inhibition of RNR activity decreases the pool of deoxyribonucleotide triphosphates available for DNA synthesis. The resulting decrease in DNA synthesis causes cell cycle arrest and growth inhibition. In addition, this agent may inhibit the nuclear enzyme poly (ADP-ribose) polymerase (PARP) 1, which prevents the repair of damaged DNA, and causes both the accumulation of single and double strand DNA breaks and the induction of apoptosis. RNR, an enzyme that catalyzes the conversion of ribonucleoside diphosphate to deoxyribonucleoside diphosphate, is essential for de novo DNA synthesis and plays an important role in cell growth; it is overexpressed in many cancer cell types and is associated with increased drug resistance, cancer cell growth and metastasis.
An orally bioavailable pan inhibitor of phosphatidylinositol-3-kinase (PI3K), with potential antineoplastic activity. Upon oral administration, pan-PI3K inhibitor CLR457 inhibits all of the PI3K kinase isoforms, which may result in apoptosis and growth inhibition in tumor cells overexpressing PI3K. Activation of the PI3K pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy.
An MDM2 (human homolog of murine double minute-2; HDM2) antagonist with potential antineoplastic activity. Upon intravenous administration, RO6839921 binds to MDM2 and prevents the binding of the MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing MDM2-p53 interaction, the proteasome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This may result in the restoration of p53 signaling, followed by p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger protein, is a negative regulator of the p53 pathway and is often overexpressed in cancer cells; p53 inhibition has been implicated in cancer cell proliferation and survival.
An anti-CD123/anti-CD3 bispecific humanized monoclonal antibody with potential immunostimulatory and antineoplastic activities. Anti-CD123/CD3 monoclonal antibody MGD006 possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for CD123, a tumor-associated antigen (TAA) overexpressed on the surface of certain tumor cells. Upon administration of MGD006, this bispecific antibody simultaneously binds to both CD3-expressing T-cells and CD123-expressing cancer cells, thereby crosslinking CD123-expressing tumor cells and cytotoxic T-lymphocytes (CTLs). This may result in potent CTL-mediated cell lysis of CD123-expressing tumor cells. CD123, the interleukin-3 receptor alpha chain, is overexpressed in a variety of hematological malignancies; its expression is low or absent in normal hematopoietic progenitors and stem cells.
An extract of the plant Dioscorea nipponica Makino and inhibitor of both the serine/threonine protein kinase Akt (protein kinase B) and members of the phosphatidylinositol 3-kinase (PI3K) family of lipid kinases, with potential antineoplastic and anti-metastatic activities. Dioscorea nipponica Makino extracted with ethyl acetate (DNE3) binds to and inhibits PI3K and Akt. This inhibits PI3K/Akt-mediated signaling and prevents both growth and survival of PI3K/Akt-overexpressing tumor cells. In addition, DNE3 increases the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2), inhibits the secretion of matrix metalloproteinases (MMPs), primarily MMP-2 and MMP-9, and inhibits the serine protease urokinase (urokinase-type plasminogen activator; u-PA). This inhibits tumor cell invasion, migration, motility, and adhesion. This agent also inhibits the activation of both cAMP response element-binding (CREB) and activating protein-1 (AP-1), and increases the expression of IkappaB (IkB), which inhibits the activation of nuclear factor-kappa B (NF-kB). These processes further contribute to this agent's anti-tumor potential in susceptible tumor cells.
An antibody-drug conjugate (ADC) composed of AGS67C, a human anti-CD37 monoclonal antibody covalently linked, via reduced cysteines and a protease cleavable linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of AGS67E binds to CD37 antigens on tumor B-cells and is rapidly internalized, thereby delivering MMAE intracellularly. Upon proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M checkpoint arrest and apoptosis in CD37-expressing tumor cells. CD37, a transmembrane glycoprotein, is overexpressed in B-cell malignancies.
A cancer vaccine composed of 3 different cytotoxic T-cell epitopes derived from the tumor-associated antigen oncofetal antigen (OFA), with potential immunostimulating and antineoplastic activities. Upon intradermal administration, anti-OFA immunotherapeutic vaccine BB-MPI-03 activates the immune system to elicit a specific cytotoxic T-lymphocyte (CTL) response against tumor cells expressing OFA. OFA, also called immature laminin receptor protein (iLRP), is expressed in fetal tissues and is overexpressed in various cancers; its expression is correlated with cancer cell survival.
An antibody-drug conjugate (ADC) composed of an antibody against a structural homolog of the urokinase-type plasminogen activator receptor (uPAR) and tumor-associated antigen, C4.4a, and conjugated with a cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, anti-C4.4a antibody-drug conjugate BAY1129980 targets and binds to C4.4a-expressing tumor cells. Upon binding and cell entry, the cytotoxic agent kills the tumor cell. C4.4a, a glycolipid-anchored membrane protein and a member of the Ly-6 family, is overexpressed by a variety of cancer cell types whereas it is minimally expressed on healthy cells.
An orally bioavailable inhibitor of Janus-associated kinase 1 (JAK1), with potential antineoplastic activity. Upon oral administration, INCB052793 specifically binds to and inhibits the phosphorylation of JAK1, which interferes with JAK-dependent signaling and may lead to an inhibition of cellular proliferation in JAK1-overexpressing tumor cells. The JAK-STAT (signal transducer and activator of transcription) signaling pathway is a major mediator of cytokine activity and is often dysregulated in a variety of tumor cell types.
A personalized peptide-based cancer vaccine comprised of one or two de novo synthesized patient-specific tumor-mutated peptides associated with glioblastoma (GB), with potential immunomodulating and antineoplastic activities. Vaccination with synthetic GB mutated tumor-specific peptides vaccine therapy APVAC2 stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the selected mutated tumor-associated peptides, which results in decreased GB growth. These peptides are specifically selected and synthesized based on the expression of the patient's own mutated tumor-associated antigens, which were detected during individual tumor genome sequencing.
A bispecific, human monoclonal antibody with potential antineoplastic activity. Anti-CD20/CD3 monoclonal antibody REGN1979 contains two antigen-recognition sites: one for human CD3, a T cell surface antigen, and one for human CD20, a tumor-associated antigen that is exclusively expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell malignancies. Upon administration, REGN1979 binds to both T-cells and CD20-expressing tumor B-cells, which cross-links the T-cells to tumor cells, and may result in a potent cytotoxic T-lymphocyte (CTL) response against CD20-expressing tumor B-cells.
An inhibitor of ataxia telangiectasia and rad3-related (ATR) kinase, a DNA damage response kinase, with potential antineoplastic activity. ATR kinase inhibitor VX-970 selectively inhibits ATR kinase activity and prevents ATR-mediated signaling in the ATR-checkpoint kinase 1 (Chk1) signaling pathway. This prevents DNA damage checkpoint activation, disrupts DNA damage repair, and induces tumor cell apoptosis. In addition, VX-970 sensitizes tumor cells to chemo- and radiotherapy. ATR, a serine/threonine protein kinase upregulated in a variety of cancer cell types, plays a key role in DNA repair, cell cycle progression, and survival; it is activated by DNA damage caused during DNA replication-associated stress.
A lipophilic cation-based triazinoindolyl-hydrazone compound and mitochondrial oxidative phosphorylation (OxPhos) inhibitor, with potential antineoplastic activity. Upon infusion, in normal cells and proliferating tumor cells where glucose is readily available, inhibition of OxPhos by VLX600 induces a hypoxia-inducible factor 1-alpha (HIF-1alpha)-dependent shift to, and an increase in glycolysis. Glycolysis alone does not produce enough energy to support the growth of tumor cells in this environment, and the induction of autophagy occurs. In the metabolically compromised tumor microenvironment, the availability of oxygen and glucose is limited due to poor vascularization and perfusion of tumor micro-areas. Tumor cells growing in this environment are thus unable to compensate for decreased mitochondrial function by increasing glycolysis. This leads to nutrient depletion, decreased energy production, induction of autophagy, tumor cell death and an inhibition of cell proliferation in quiescent tumor cells. Mitochondrial OxPhos, which is hyperactivated in cancer cells, plays a key role in the promotion of cancer cell proliferation.
A fully human combinatorial antibody library (HuCAL)-derived monoclonal antibody targeting the B-cell-activating factor receptor (BAFF-R), with potential anti-inflammatory and antineoplastic activities. Upon administration of HuCAL-based antibody VAY736, the antibody targets and binds to BAFF-R, which inhibits both BAFF/BAFF-R interaction and BAFF-R-mediated signaling. This may decrease cell growth in tumor cells expressing BAFF-R. BAFF-R, also known as tumor necrosis factor receptor superfamily member 13C, is overexpressed in certain tumor cell types and autoimmune diseases. In cancer cells, BAFF-R plays a key role in B-cell proliferation and survival. VAY736 was developed using HuCAL technology.
A genetically engineered epothilone analog with potential antineoplastic activity. Upon administration, epothilone analog UTD1 binds to tubulin, induces microtubule polymerization and stabilizes microtubules against depolymerization, which may result in the inhibition of cell division, the induction of G2/M arrest, and apoptosis. Compared to first-generation epothilones, this agent exhibits greater safety and enhanced activity against certain multidrug-resistant (MDR) tumors.
An orally bioavailable fatty acid synthase (FASN) inhibitor, with potential antineoplastic activity. Upon administration, TVB-2640 binds to and blocks FASN, which prevents the synthesis of palmitate needed for tumor cell growth and survival. This leads to a reduction in cell signaling, an induction of tumor cell apoptosis and the inhibition of cell proliferation in susceptible tumor cells. FASN, an enzyme responsible for the de novo synthesis of palmitic acid, is overexpressed in tumor cells and plays a key role in tumor metabolism, lipid signaling, tumor cell survival and drug resistance; tumor cells are dependent on increased fatty acid production for their enhanced metabolic needs and rapid growth.
An orally bioavailable extract from the yellow to brown gum-resin of the gamboge tree (genus Garcinia) belonging to the Clusiaceae (or Guttiferae) family, with potential anti-inflammatory and antineoplastic activities. Gamboge resin extract TSB-9-W1 contains various active ingredients, including gambogic acid, formoxanthone A, betulin, betulinic acid, morellic acid, isomorellic acid, isogambogic acid, isomorellinol and desoxymorellin. Upon oral administration, the various active components of the gamboge resin extract TSB-9-W1 may bind to and inhibit the activity of a variety of cancer-related proteins, may induce apoptosis, and may exert cytotoxic activity on tumor cells, thereby inhibiting tumor cell proliferation. TSB-9 is derived from TSB-14, which is the acetone-extract of gamboge resin, and pulverized into powder form; TSB-9 is 90% extract and 10% brown sugar. TSB-9-W1 is a milled form of TSB-9 with a particle size of 5 micrometers.
short interfering RNAs (siRNAs) directed against polo-like kinase 1 (PLK1, STPK13), with potential antineoplastic activity. Upon administration of lipid-encapsulated anti-PLK1 siRNA TKM-PLK1, siRNA binds to PLK1 mRNA, which results in the inhibition of both the translation and expression of the PLK1 protein. Blockage of PLK1 expression prevents proper tumor cell mitosis, causes cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of PLK1-overexpressing tumor cells. PLK1, named after the polo gene of Drosophila melanogaster, is a serine/threonine kinase crucial in the regulation of mitosis; its expression is upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation. The pegylated lipid bilayer of SNALP provides stability and protects siRNA degradation; it facilitates uptake into the cell and release from endosomes.
An agonistic tetravalent nanobody, in which the four single, high affinity heavy chain variable domain (VHH) antibodies are separated by a peptide linker, targeting death receptor type 5 (DR5), with potential antineoplastic activity. Upon administration, DR5-targeting tetrameric nanobody agonist TAS266, with its four DR5-specific single-chain antibodies, specifically binds to and activates DR5 receptors. This results in the activation of caspase cascades and induction of apoptosis in DR5-expressing tumor cells. DR5, a cell surface receptor and member of the tumor necrosis factor (TNF)-receptor superfamily, triggers apoptosis. Compared to certain anti-DR5 antibody agonists, TAS266 shows increased receptor activation.
An orally bioavailable inhibitor of the serine/threonine protein kinase aurora A, with potential antimitotic and antineoplastic activities. Upon intravenous administration, aurora A kinase inhibitor TAS-119 binds to and inhibits aurora A kinase, which may result in disruption of the assembly of the mitotic spindle apparatus, disruption of chromosome segregation, inhibition of cell division and the induction of apoptosis in cells overexpressing aurora A kinase. Aurora A kinase localizes to the spindle poles and to spindle microtubules during mitosis; it plays an essential role in the regulation of spindle assembly. Aurora kinase A is overexpressed in a wide variety of cancers.
An orally bioavailable inhibitor of both deoxyuridine triphosphatase (dUTPase) and dihydropyrimidine dehydrogenase (DPD), with potential antineoplastic adjuvant activity. Upon oral administration in combination with a prodrug of the pyrimidine antagonist 5-fluorouracil (5-FU), TAS-114 inhibits (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. This prevents first-pass metabolism of 5-FU, allowing oral administration of the 5-FU prodrug and increasing the efficacy of 5-FU. In addition, as a dUTPase inhibitor, TAS-114 enhances the antitumor activity of 5-FU by preventing the hydrolysis and breakdown of 5-fluoro-deoxyuridine triphosphate (FdUTP) and deoxyuridine triphosphate (dUTP), which are active metabolites of 5-FU. This promotes DNA polymerase-dependent incorporation of these antimetabolites into DNA and leads to DNA damage and tumor cell death. Co-administration with TAS-114 allows lower dosing of 5-FU prodrugs, which decreases 5-FU-related toxicity, while maintaining therapeutic levels of 5-FU at the tumor site.
An antibody-drug conjugate (ADC) composed of the recombinant humanized anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab linked, via a cleavable linker, to the duocarmycin prodrug, seco-duocarmycin-hydroxybenzamide-azaindole (seco-DUBA), with potential antineoplastic activity. Upon administration of trastuzumab duocarmazine, the trastuzumab moiety binds to HER2 on the tumor cell surface, which triggers the endocytosis of this agent. The linker is then cleaved inside the tumor cell by proteases at the dipeptide valine-citrulline (vc), and releases the active moiety, duocarmycin. Duocarmycin binds to the minor groove of DNA, alkylates adenine at the N3 position, and induces cell death. In addition, trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells that overexpress HER2. HER2 is overexpressed by many carcinomas and is associated with a poor prognosis.
A soluble fusion protein containing the extracellular domain of the activin receptor type 2B (ACVR2B or ActRIIB) fused to a human Fc domain, with potential antineoplastic activity. Upon intravenous administration, STM 434 selectively binds to the growth factor activin A, thereby preventing its binding to and the activation of endogenous ActRIIB. This prevents activin A/ActRIIB-mediated signaling and inhibits the proliferation of activin A-overexpressing tumor cells. Activin A, a member of the transforming growth factor beta (TGF-beta) superfamily, is overexpressed in a variety of cancers and plays a key role in promoting cancer cell proliferation, migration, and survival.
A plasmid DNA vaccine containing the mammalian expression vector pUMVC3 (pNGVL3) encoding epitopes of CD105 (Endoglin), Y-box binding protein 1 (Yb-1), SRY-box 2 (SOX2), cadherin 3 (CDH3), and murine double minute 2 (MDM2) proteins, with potential immunomodulating and antineoplastic activities. Upon intradermal administration of pUMVC3-CD105/Yb-1/SOX2/CDH3/MDM2-epitopes plasmid DNA vaccine, the plasmid transfects cells and the peptides are expressed. This generates a specific memory Th1 (T-helper) cell immune response, stimulates secretion of cytokines by the T cells and leads to a cytotoxic T-lymphocyte (CTL) response against CD105/Yb-1/SOX2/CDH3/MDM2-expressing tumor cells. CD105/Yb-1/SOX2/CDH3/MDM2 proteins are highly immunogenic tumor associated antigens that are overexpressed in breast cancer. Additionally, these antigens are associated with breast cancer stem cells and with epithelial to mesenchymal transformation (EMT).
An orally available, nonsteroidal selective estrogen receptor degrader (SERD), with potential antineoplastic activity. Upon oral administration, SERD SRN-927 specifically binds to the estrogen receptor (ER) and induces a conformational change that results in the degradation of the receptor. This prevents ER-mediated signaling and inhibits the growth and survival of ER-expressing cancer cells.
A sulfonamide carbonic anhydrase inhibitor with potential antineoplastic activity. Upon administration, CAIX inhibitor SLC-0111 inhibits tumor-associated carbonic anhydrase IX (CAIX), an hypoxia-inducible transmembrane glycoprotein that catalyzes the reversible reaction and rapid interconversion of carbon dioxide and water to carbonic acid, protons, and bicarbonate ions. This prevents both the acidification of the tumor's extracellular microenvironment and cytoplasmic alkalization. This increases cell death in CAIX-expressing, hypoxic tumors. CAIX is overexpressed in various tumors and plays a key role in intra- and extracellular pH regulation, cancer cell progression, survival, migration and invasion; it is also involved in resistance to both chemo- and radiotherapy.
A cell-based cancer vaccine comprised of dendritic cells (DCs) pulsed with various, synthetic glioma-associated antigen (GAA) peptides, with potential antineoplastic activity. Upon subcutaneous administration, the glioma-associated peptide-loaded DC vaccine SL-701 exposes the immune system to various GAA peptides. This may stimulate both anti-tumoral cytotoxic T lymphocyte (CTL) and antibody responses against the GAA-expressing glioma cells, which may result in tumor cell lysis.
An antibody-drug conjugate (ADC) containing an engineered cysteine monoclonal antibody (EC-mAb), directed against the extracellular domain of the human CD70 molecule, conjugated to the synthetic, cytotoxic, DNA minor-groove crosslinking agent, pyrrolobenzodiazepine (PBD) dimer, via a stable, protease-cleavable, peptide-based linker, with potential antineoplastic activity. The anti-CD70 antibody moiety of the anti-CD70 antibody-drug conjugate SGN-CD70A selectively binds to the extracellular domain of CD70 on tumor cell surfaces. Upon internalization, the PBD dimer moiety is released and covalently binds, through its imine moieties, to the N2 positions of guanines on opposite strands of DNA. This induces DNA double strand breaks and inhibits DNA replication, which lead to the inhibition of cell growth of tumor cells that overexpress CD70. CD70, the ligand for the costimulatory receptor CD27 and a member of the tumor necrosis factor (TNF) family, is found on the surfaces of various types of cancer cells. The cysteine moiety of the EC-mAb allows for the stable conjugation of the PBD to the antibody.
An immunoconjugate consisting of anti-carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) conjugated to a cytotoxic agent, with potential antineoplastic activity. Upon administration of anti-CEACAM5 antibody-drug conjugate SAR408701, the antibody moiety targets CEACAM5 on tumor cells. Upon antibody/antigen binding and internalization, the immunoconjugate releases the cytotoxic agent, which results in tumor cell death. CEACAM5, a member of the CEA family of proteins that plays a key role in cell migration, cell invasion, and cell adhesion, is overexpressed by a variety of cancer cell types.
An orally available protein and insulin sensitizer with anti-hyperglycemic activity. Upon oral administration, S-707106 increases the sensitivity of target organs to insulin, through an as of yet not fully elucidated mechanism. This agent may lower blood glucose levels.
An anti-carcinoembryonic antigen (CEA)/anti-CD3 bispecific monoclonal antibody with potential antineoplastic activity. Anti-CEA/CD3 monoclonal antibody RO6958688 contains two antigen-recognition sites: one for human CD3, a T-cell surface antigen, and one for human CEA, a tumor-associated antigen that is specifically expressed on certain tumor cells. Upon intravenous administration, RO6958688 binds to both T-cells and CEA-expressing tumor cells, which cross-links the T-cells with the tumor cells. This may result in a potent cytotoxic T-lymphocyte (CTL) response against CEA-expressing tumor cells. CEA is overexpressed in many cancer cell types.
A recombinant, humanized monoclonal antibody targeting the cancer stem cell (CSC) antigen CD44, with potential immunomodulating and antineoplastic activities. Upon administration, RO5429083 binds to the constant region of the extracellular domain of CD44, thereby preventing the activation of various CD44-mediated signal transduction pathways. This may lead to a reduction in the proliferation of CD44-expressing tumor stem cells. CD44, a transmembrane glycoprotein and hyaluronic acid receptor, is expressed in healthy tissue and overexpressed in numerous cancer cell types; it plays a key role in tumor cell proliferation, migration and survival.
An orally active, small molecule inhibitor of hypoxia inducible factor (HIF)-2alpha, with potential antineoplastic activity. Upon oral administration, HIF-2alpha inhibitor PT2385 allosterically binds to HIF-2alpha, thereby preventing HIF-2alpha heterodimerization and its subsequent binding to DNA. This results in decreased transcription and expression of HIF-2alpha downstream target genes, many of which regulate tumor cell growth and survival. Blocking HIF-2alpha reduces the proliferation of HIF-2alpha-expressing tumor cells. HIF-2alpha, a heterodimeric transcription factor overexpressed in many cancers, promotes tumorigenesis.
An orally available, small molecule, third-generation, irreversible inhibitor of epidermal growth factor receptor (EGFR) mutant (EGFRm) forms with potential antineoplastic activity. EGFR inhibitor PF-06459988 specifically binds to and inhibits mutant forms of EGFR, including the secondary acquired resistance mutation T790M, which prevents EGFR-mediated signaling and leads to cell death in EGFRm-expressing tumor cells. Compared to some other EGFR inhibitors, PF-06459988 may have therapeutic benefits in tumors with T790M-mediated drug resistance. This agent shows minimal activity against wild-type EGFR (WT EGFR), and does not cause dose-limiting toxicities that are seen with the use of non-selective EGFR inhibitors, which also inhibit WT EGFR. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
A peptide vaccine consisting of a peptide derived from isocitrate dehydrogenase 1 (IDH1) containing the point mutation R132H (IDH1R132H), with potential antineoplastic activity. Intradermal vaccination with the IDH1R132H-specific peptide vaccine PEPIDH1M may stimulate the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells that express the IDH1R132H protein. The IDH1 point mutation of amino acid residue 132 is highly expressed in gliomas and is associated with increased production of the oncometabolite R-2-hydroxyglutarate (2HG).
An orally bioavailable inhibitor of one or more signal transducer and activator of transcription (STAT) protein(s), with potential antineoplastic activity. Upon oral administration, OPB-111077 binds to and inhibits the phosphorylation of STATs. This prevents binding of STATs to DNA sequences on a variety of STAT-responsive gene promoters, which may result in the inhibition of both STAT-mediated transcription and tumor cell proliferation. STATs are constitutively activated in a variety of cancers and play a key role in tumor cell proliferation.
A monoclonal antibody against mannan-binding lectin (MBL)-associated serine protease-2 (MASP-2), with potential anti-thrombotic and immunomodulating activities. Upon subcutaneous administration, OMS721 binds to and inhibits MASP-2. This prevents the activation of MASP-2, the cleavage of certain complement components, and the activation of the complement lectin pathway. This inhibits complement deposition and complement-induced thrombus formation. MASP-2, a pro-inflammatory protein, plays a key role in the activation of the lectin complement pathway, which is a key component in the immune system, and is associated with complement-mediated diseases, such as thrombotic microangiopathies (TMAs), which includes hematopoietic stem cell transplant (HSCT)-related TMA, atypical hemolytic uremic syndrome (aHUS), and thrombotic thrombocytopenic purpura (TTP).
A bispecific monoclonal antibody directed against both the Notch ligand delta-like 4 (DLL4) and the human tyrosine kinase vascular endothelial growth factor (VEGF), with potential anti-angiogenic and antineoplastic activities. The anti-DLL4 moiety of anti-DLL4/VEGF monoclonal antibody OMP-305B83 specifically binds to DLL4, prevents its interaction with Notch receptors, and inhibits Notch-mediated signaling and gene transcription, which may both block tumor angiogenesis and inhibit tumor cell growth. The anti-VEGF moiety binds to VEGF and prevents the binding of VEGF to its receptor, which blocks VEGF-mediated signaling and further inhibits the growth and maintenance of tumor blood vessels. The expression of DLL4 is highly restricted to the vascular endothelium; DLL4/Notch signaling is required for the development of functional tumor blood vessels. The expression of the pro-angiogenic growth factor VEGF is associated with tumor angiogenesis and tumor cell proliferation and invasion.
An orally available inhibitor of both the steroid 17-alpha-hydroxylase/C17,20 lyase (CYP17A1 or CYP17) and androgen receptor (AR), with potential anti-androgen and antineoplastic activities. Upon oral administration, CYP17/AR inhibitor ODM 204 selectively inhibits the enzymatic activity of CYP17A1 in both the testes and adrenal glands, thereby inhibiting androgen production. This may both decrease androgen-dependent growth signaling and inhibit the proliferation of androgen-dependent tumor cells. In addition, ODM 204 binds to ARs in target tissues and inhibits androgen-induced receptor activation and AR nuclear translocation, which prevents the binding to and transcription of AR-responsive genes. This leads to an inhibition of growth in AR-expressing prostate cancer cells. The cytochrome P450 enzyme CYP17A1, which is localized to the endoplasmic reticulum, exhibits both 17alpha-hydroxylase and 17,20-lyase activities.
An orally available inhibitor of the human vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptors (FGFRs), with potential antiangiogenic and antineoplastic activities. VEGFR/FGFR inhibitor ODM-203 inhibits both VEGFRs and FGFRs, which may result in the inhibition of VEGFR- and FGFR-mediated signaling. This leads to an inhibition of angiogenesis and cell proliferation in tumor cells overexpressing VEGFR and/or FGFR. Both VEGFRs and FGFRs belong to the superfamily of receptor tyrosine kinases and are upregulated in various tumor cell types.
A replication-competent oncolytic, telomerase-specific adenovirus serotype 5 (Ad5), with potential antineoplastic activity. OBP-301 contains the human telomerase reverse transcriptase (hTERT) gene promoter sequence that drives the expression of the E1A and E1B genes, and is linked to an internal ribosomal entry site (IRES). Upon administration, OBP-301 selectively infects and replicates in cancer cells that are expressing telomerase, which causes cell lysis. This adenovirus does not infect or replicate in normal, healthy cells. OBP-301 may also potentially be used as a chemosensitizer. hTERT, which encodes for the catalytic protein subunit of telomerase, is overexpressed in a variety of cancer cell types but not in normal, healthy cells. The insertion of an IRES further improves selectivity towards telomerase-expressing cancer cells.
A carbohydrate-based vaccine comprised of the Globo H hexasaccharide 1 (Globo H) antigen conjugated to DT-CRM197, a non-toxic, mutated form of diphtheria toxin (DT), with potential immunostimulating and antineoplastic activities. Upon administration of Globo H-DT vaccine OBI-833, the carbohydrate antigen Globo H may stimulate a cytotoxic T-lymphocyte (CTL) response against Globo H-expressing tumor cells, thereby decreasing tumor cell proliferation. The hexasaccharide Globo H is a tumor-associated antigen (TAA) commonly found on a variety of tumor cells. DT-CRM197, also called diphtheria toxin cross-reacting material 197, is used to increase the immunogenicity of the Globo H carbohydrate antigen.
An orally available inhibitor of DNA-dependent protein kinase (DNA-PK), with potential antineoplastic and chemo/radiosensitizing activities. Upon oral administration, the DNA-PK inhibitor MSC2490484A binds to and inhibits the activity of DNA-PK. This inhibits the ability of tumor cells to repair damaged DNA, which may lead to a reduction in cellular proliferation of cancer cells expressing DNA-PK. DNA-PK, a serine/threonine kinase and a member of the PI3K-related kinase subfamily of protein kinases, is activated upon DNA damage and plays a key role in repairing DNA double-strand breaks (DSBs) via the DNA nonhomologous end joining (NHEJ) pathway. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy.
A designed ankyrin repeat proteins (DARPin)-based agent targeting vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), with potential antiangiogenic and antineoplastic activities. Compared to antibodies, DARPins are small in size, have favorable pharmacokinetics and allow for both high affinity binding and efficacy. Upon administration, the VEGF/HGF-targeting DARPin MP0250 binds to and inhibits both HGF and VEGF. This prevents HGF- and VEGF-mediated signaling, and inhibits the growth of HGF/VEGF-overexpressing tumor cells. This agent also prevents osteolysis, due to the inhibitory effect on HGF signaling. HGF and VEGF are overexpressed in a variety of cancer cell types and are associated with increased cell proliferation, migration and adhesion.
An anti-prostate specific membrane antigen (PSMA)/anti-CD3 bispecific humanized monoclonal antibody, with potential immunostimulatory and antineoplastic activities. Anti-PSMA/CD3 monoclonal antibody MOR209/ES414 possesses two antigen-recognition sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for PSMA, a tumor-associated antigen (TAA) overexpressed on the surface of prostate tumor cells. Upon intravenous administration of MOR209/ES414, this bispecific antibody simultaneously binds to both CD3-expressing T-cells and PSMA-expressing cancer cells, thereby crosslinking PSMA-expressing tumor cells and cytotoxic T-lymphocytes (CTLs). This results in CTL-mediated cancer cell lysis of prostate cancer cells expressing PSMA.
An orally bioavailable inhibitor of human homolog of double minute 2 (HDM2), with potential antineoplastic activity. Upon oral administration, HDM2 inhibitor MK-8242 inhibits the binding of the HDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this HDM2-p53 interaction, the degradation of p53 is inhibited, which may result in the restoration of p53 signaling. This induces p53-mediated tumor cell apoptosis. HDM2 is a member of the RING finger-type family of E3 ubiquitin protein ligases and targets p53 for degradation; it is often overexpressed in cancer cells and has been implicated in cancer cell proliferation and survival.
An anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR) agonistic monoclonal antibody (MoAb) with potential immunomodulating activity. Anti-GITR monoclonal antibody MK-4166 binds to and activates GITRs found on multiple types of T-cells. This stimulates the immune system and induces both the activation and proliferation of tumor-antigen-specific T effector cells, and suppresses the function of activated T regulatory cells. This leads to tumor cell eradication. Also, this agent is shown to act synergistically with chemotherapeutic drugs in multiple cancer models. GITR, a member of the TNF receptor superfamily, is expressed on the surface of multiple types of immune cells, including regulatory T-cells, effector T-cells, B-cells, and natural killer (NK) cells.
An anti-glycoprotein A33 (gpA33)/anti-CD3 bispecific humanized monoclonal antibody with potential immunostimulatory and antineoplastic activities. Anti-gpA33/CD3 monoclonal antibody MGD007 possesses two antigen-recognition sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for gpA33, a tumor-associated antigen (TAA) overexpressed on the surface of certain tumor cells. Upon administration of MGD007, this bispecific antibody simultaneously binds to both CD3-expressing T-cells and gpA33-expressing cancer cells, thereby crosslinking cytotoxic T-lymphocytes (CTLs) to gpA33-expressing tumor cells. This may result in CTL-mediated cell lysis of the crosslinked tumor cells. The gpA33 antigen, a member of the immunoglobulin superfamily, is expressed in certain malignancies, including colon and gastrointestinal cancers.
An 86 amino-acid long polypeptide fragment of a recombinant form of human apolipoprotein (a) (apo(a)) kringle V, with potential anti-angiogenic and antineoplastic activities. Although the exact mechanism of action has yet to be fully elucidated, upon administration, recombinant human apo(a) kringle V MG1102 inhibits the fibronectin-mediated migration of endothelial cells, binds to and blocks the activity of alpha 3 beta 1 integrin (a3b1 integrin), inhibits the activation of focal adhesion kinase (FAK) and FAK-mediated signaling, and leads to the inhibition of the p130 Crk-associated substrate (p130CAS)-c-Jun NH2-terminal kinase (JNK) pathway. This inhibits tumor angiogenesis, induces mitochondrial-mediated apoptosis of tumor cells and tumor-associated endothelial cells, and suppresses tumor growth and metastasis. Apo(a), a glycoprotein component of human lipoprotein(a), contains repeated kringle domains; certain kringle domains of apo(a), including the plasminogen kringle V homolog (KV), have anti-angiogenic effects.
A human monoclonal antibody against the fibroblast growth factor receptor type 3 (FGFR3), with potential antineoplastic activity. Upon administration, the anti-FGFR3 antibody MFGR1877S binds to and inhibits FGFR3, which may result in the inhibition of both FGFR3 phosphorylation and FGFR3-mediated signal transduction pathways. This results in the inhibition of cell proliferation and the induction of cell death in FGFR3-expressing tumor cells. FGFR3, upregulated or mutated in many tumor cell types, is a receptor tyrosine kinase, and plays a key role in tumor cell proliferation.
An agonistic monoclonal antibody against the co-stimulatory receptor OX40 (CD134), with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, anti-OX40 monoclonal antibody MEDI6469 selectively binds to and activates OX40. OX40 activation induces proliferation of effector T-lymphocytes. In the presence of tumor-associated antigens (TAAs), this may promote an immune response against the TAA-expressing tumor cells. OX40, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on T-lymphocytes and provides a co-stimulatory signal for the proliferation and survival of activated T-cells.
A neutralizing, human monoclonal antibody against the hepatitis C virus (HCV) E2 envelope glycoprotein, with potential immunomodulatory and antiviral activities against HCV. Upon administration, anti-HCV E2 monoclonal antibody MBL-HCV1 recognizes and binds to the E2 glycoprotein of HCV. This suppresses HCV load and provides passive immunization against HCV. This may prevent both infection by HCV in immunocompromised patients and hepatitis C-related liver disease. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family.
An orally available inhibitor of all members of the serine/threonine protein kinase Raf family, including A-Raf, B-Raf and C-Raf protein kinases, with potential antineoplastic activity. Upon administration, pan-RAF kinase inhibitor LY3009120 inhibits Raf-mediated signal transduction pathways, which may inhibit tumor cell growth. Raf protein kinases play a key role in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival.
A humanized monoclonal antibody (MoAb) targeting the peptide hormone hepcidin, with potential anti-anemic activity. Upon intravenous administration, anti-hepcidin MoAb LY2787106 binds to hepcidin and prevents it from binding to the iron exporting protein ferroportin, which is expressed on both the basolateral surface of gastrointestinal (GI) enterocytes and the plasma membrane of macrophages. This prevents hepcidin-induced internalization and degradation of ferroportin and increases ferroportin-mediated iron export, thus increasing iron export from macrophages and iron absorption by enterocytes. This normalizes plasma iron levels, increases erythropoiesis and may inhibit anemia. Hepcidin, produced in hepatocytes, plays a key role in the homeostasis of systemic iron; it is upregulated during acute and chronic inflammation in response to cytokines and, in certain cancers, may contribute to cancer-associated anemia.
An antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody against the stem cell factor receptor c-Kit (SCFR) and conjugated, via a non-cleavable linker, to the cytotoxic agent maytansine, with potential antineoplastic activity. The monoclonal antibody moiety of anti c-KIT ADC LOP628 targets and binds to the cell surface antigen c-Kit. After antibody-antigen interaction followed by internalization, the maytansine moiety binds to tubulin, inhibits microtubule assembly, and induces microtubule disassembly. This leads to a disruption of mitosis and the inhibition of cell proliferation in cancer cells expressing c-Kit. c-Kit, a transmembrane protein and receptor tyrosine kinase, is overexpressed in solid tumors and hematological malignancies; it plays a key role in the regulation of cell differentiation and proliferation.
An orally available small molecule agonist of the platelet thrombopoietin (TPO) receptor (TPOR; MPL), with potential megakaryopoiesis stimulating activity. Upon administration, TPOR agonist LGD-4665 mimics TPO and binds to TPOR. This stimulates TPOR and leads to the proliferation and differentiation of megakaryocytes in the bone marrow. This increases the production of blood platelets and decreases bleeding in thrombocytopenic patients. TPOR is a cytokine receptor and member of the hematopoietin receptor superfamily.
A lyophilized formulation of DOS47, an immunoconjugate composed of AFAIKL2, a recombinant camelid single-domain antibody which recognizes carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), and the enzyme urease derived from the plant Canavalia ensiformis (Jack bean), with potential antineoplastic activity. Upon intravenous administration, the AFAIKL2 antibody fragment moiety of L-DOS47 specifically targets and binds to CEACAM6 expressed on certain tumor cells. In turn, the urease moiety of L-DOS47 catalyzes the hydrolysis of urea into ammonia, which is further hydrolyzed to produce hydroxyl ions, and causes a locally increased concentration of the toxic waste product ammonia, which under normal conditions is converted into the nontoxic substance urea via the urea cycle. This increases the pH of the tumor microenvironment and alkalinizes the highly acidic environment that is needed for cancer cell survival and proliferation. In addition, the ammonia diffuses into cancer cells and exerts a cytotoxic effect. Altogether, this leads to cell death of CEACAM6-expressing cancer cells. The naturally-occurring enzyme urease catalyzes the hydrolysis of urea into ammonia and carbon dioxide. CEACAM6, a tumor-associated antigen and CEA family member, is overexpressed in a variety of tumor cells and plays a key role in tumor initiation, progression, metastasis and survival.
A lipophilic, orally available inhibitor of both Src kinase activity and tubulin polymerization, with potential antineoplastic activity. Upon oral administration, src/tubulin inhibitor KX02 binds to and inhibits the activity of Src kinase. This inhibits both downstream signaling and the proliferation of Src kinase-expressing tumor cells. KX02 also binds to tubulin heterodimers and inhibits microtubule polymerization, thereby disrupting microtubule formation, mitosis, and further proliferation. Src, a non-receptor tyrosine kinase, is overexpressed in a variety of tumor cell types and plays a key role in tumor cell proliferation, angiogenesis, migration, and metastasis.
A non-fucosylated monoclonal antibody directed against the ephrin receptor A3 (EphA3), with potential antineoplastic activity. Upon administration, anti-EphA3 monoclonal antibody KB004 selectively binds to tumor cells expressing EphA3. This blocks both EphA3 activation and EphA3-mediated signaling, and induces apoptosis in EphA3-expressing tumor cells. In addition, KB004 can stimulate antibody dependent cell-mediated cytotoxicity (ADCC) against EphA3-expressing tumor cells. This agent also prevents tumor cell proliferation by inhibiting both EphA3 signaling and proliferation of endothelial cells in the tumor vasculature. The cell-surface receptor EphA3, a member of the ephrin family of receptor tyrosine kinases (RTKs) that are involved in mammalian development, is overexpressed by a variety of tumor types but is not expressed in normal healthy adult tissues. It plays an important role in tumor cell proliferation. Non-fucosylation of the antibody enhances its ADCC activity.
An antisense oligonucleotide targeting the androgen receptor (AR) mRNA, with potential antineoplastic activity. Upon intravenous administration, AZD5312 hybridizes with AR mRNA, which blocks translation of the AR protein. This both inhibits AR-induced tumor cell growth and promotes apoptosis in AR-overexpressing tumor cells. AR is overexpressed in certain breast and prostate cancers and is involved in tumor cell proliferation and survival.
A DNA vaccine consisting of a plasmid encoding a modified, inactive form of the human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase which synthesizes telomeric DNA at the chromosome ends, fused to ubiquitin, with potential immunostimulating and antineoplastic activities. Upon intradermal vaccination of the hTERT encoding DNA vaccine INVAC-1 in combination with electroporation, hTERT protein is expressed and activates the immune system to mount a cytotoxic T-cell (CTL) response against telomerase-expressing tumor cells, which may result in tumor cell death. Telomerase prolongs the functional lifespan of cells via the restoration and maintenance of telomere length. Abnormally activated in tumorigenesis, telomerase is expressed in the majority of human cancer cells, but its expression is low or non-existent in normal cells. hTERT conjugation to ubiquitin, a 76 amino-acid peptide involved in the regulation of normal protein intracellular turnover in the cytoplasm, enhances proteasome-dependent degradation of the hTERT protein, increases hTERT presentation by major histocompatibility complex (MHC) class I molecules and results in an increased immune response against hTERT.
A plasmid DNA vaccine encoding the human pro-inflammatory cytokine interleukin-12 (IL-12) with potential immunoactivating activity. Upon intramuscular delivery by electroporation of DNA plasmid encoding interleukin-12 INO-9012, IL-12 is translated in cells and activates the immune system by promoting the activation of natural killer cells (NK cells), inducing secretion of interferon-gamma and promoting cytotoxic T-cell responses against tumor cells. This may result in both immune-mediated tumor cell death and the inhibition of tumor cell proliferation.
A DNA vaccine consisting of a plasmid encoding the full-length sequence of the tumor-associated antigen (TAA) human telomerase reverse transcriptase (hTERT), which is the catalytic subunit of human telomerase and synthesizes telomeric DNA at the chromosome ends, containing two immunogenic mutations, with potential immunostimulating and antineoplastic activities. Upon intradermal vaccination of the hTERT encoding DNA vaccine INO-1400 in combination with electroporation, hTERT protein is expressed and activates the immune system to mount a cytotoxic T-cell (CTL) response against telomerase-expressing tumor cells, which may result in tumor cell death. Telomerase prolongs the functional lifespan of cells via the restoration and maintenance of telomere length. Abnormally activated in tumorigenesis, telomerase is expressed in the majority of human cancer cells, but its expression is low or non-existent in normal cells.
An oligonucleotide targeted to the mRNA of MYD88 L265P, a mutant form of the linker protein MYD88, with potential antitumor activity. Anti-MYD88 oligonucleotide IMO-8400 binds to and inhibits the translation of mutated MYD88 L265P mRNA. This prevents overactivation of signaling pathways mediated by toll-like receptors (TLRs) 7, 8, and 9, nuclear factor-kappa B (NF-kB) activity, Janus-associated kinases-signal transducer and activator of transcription (JAK-STAT) signaling and the production of various cytokines. Together, this leads to an induction of apoptosis and an inhibition of tumor cell proliferation in MYD88 L265P-expressing tumor cells. MYD88, a key adaptor protein in the TLR signaling pathway, is mutated in a variety of B-cell lymphomas, including Waldenstrom's macroglobulinemia (WM) and activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL).
A nanoparticle albumin-bound formulation of a thiocolchicine dimer, an inhibitor of both microtubule and topoisomerase I (TOP1), with antineoplastic and vascular disrupting activities. Upon administration of nanoparticle albumin-bound thiocolchicine dimer nab-5404, this agent binds to tubulin and inhibits its polymerization, which blocks mitotic spindle formation and leads to cell cycle arrest and tumor endothelial cell apoptosis. This disrupts the tumor vasculature and leads to tumor necrosis. In addition, nab-5404 binds to topoisomerase I (TOPI) and inhibits its activity. This results in the inhibition of the repair of single-strand DNA breaks, DNA replication, and tumor cell growth in susceptible tumor cell populations. The nanoparticle albumin-based formulation permits the albumin-mediated endocytosis of the thiocolchicine dimer by tumor cells and endothelial cells.
An engineered lentiviral vector targeting dendritic cells (DCs) and containing nucleic acids encoding for the human tumor-associated cancer-testis antigen NY-ESO-1, with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the DC-targeting lentiviral vector ID-LV305 targets and binds to dermal DCs via the DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) receptor. Upon internalization of the vector, the NY-ESO-1 protein is expressed, stimulates DC maturation and activates the immune system to mount a cytotoxic T-lymphocyte (CTL) response against NY-ESO-1-expressing cells, which may result in tumor cell lysis. NY-ESO-1 is expressed in normal testes and on the surfaces of various tumor cells, and plays a key role in tumor cell proliferation and survival.
A humanized monoclonal antibody targeting the human cell surface antigen CD47, with potential immunostimulating and antineoplastic activities. Upon administration, anti-CD47 monoclonal antibody Hu5F9-G4 selectively binds to CD47 expressed on tumor cells and blocks the interaction of CD47 with its ligand signal regulatory protein alpha (SIRPa), a protein expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling, allows the activation of macrophages, through the induction of pro-phagocytic signaling mediated by calreticulin, which is specifically expressed on the surface of tumor cells, and results in specific tumor cell phagocytosis. In addition, blocking CD47 signaling activates an anti-tumor T-lymphocyte immune response and T-mediated cell killing. CD47, a tumor associated antigen expressed on normal, healthy hematopoietic stem cells (HSC), is overexpressed on the surface of a variety of cancer cells. Expression of CD47, and interaction with SIRP-alpha, leads to inhibition of macrophages and protects cancer cells from phagocytosis thereby allowing cancer cells to proliferate.
An orally bioavailable human double minute 2 homolog (HDM2) inhibitor with potential antineoplastic activity. HDM2 inhibitor HDM201 inhibits the binding of the HDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this HDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited, which may result in the restoration of both p53 signaling and p53-mediated induction of tumor cell apoptosis. HDM2, a zinc finger protein and negative regulator of the p53 pathway, is often overexpressed in cancer cells and has been implicated in cancer cell proliferation and survival.
A therapeutic cancer vaccine consisting of four epitopes derived from the human telomerase reverse transcriptase (hTERT), the catalytic subunit of human telomerase, including hTERT (540-548) acetate, hTERT (611-626) acetate, hTERT (672-686) acetate and hTERT (766-780) acetate, emulsified individually in the adjuvant montanide ISA-51 VG and administered with the immune response modifier (IRM) imiquimod, with potential immunostimulating and antineoplastic activities. Each hTERT peptide emulsion is administered individually by intradermal injection. Subsequently, imiquimod is applied topically to the injection site(s). Vaccination with GX 301 may elicit a cytotoxic T-cell (CTL) response against telomerase-expressing tumor cells. Telomerase is expressed in the majority of human cancer cells, infrequently expressed in normal cells, and is directly linked to tumorigenesis. Imiquimod stimulates cytokine production through the activation of toll-like receptor 7 (TLR-7), and also exhibits antiproliferative effects. Montanide ISA-51, also known as incomplete Freund's adjuvant (IFA), is a stabilized water-in-oil emulsion containing mineral oil with mannide oleate, which contains vegetable-grade (VG) oleic acid derived from olive oil. ISA-51 non-specifically stimulates cell-mediated immune responses to antigens.
An immunotherapeutic agent targeting the tumor-associated antigen (TAA), preferentially expressed antigen of melanoma (PRAME), with potential antineoplastic activity.
An immunotherapeutic composed of the Wilms tumor 1 (WT1) and an as of yet undisclosed adjuvant, with potential antineoplastic activity. Upon administration, the immune system may be stimulated to exert a cytotoxic T-lymphocyte (CTL) response against WT1-expressing tumor cells. The adjuvant stimulates the immune system's response to WT1. WT1, a tumor-associated antigen (TAA) and transcription factor, is overexpressed in a variety of tumor cell types.
An immunotherapeutic agent targeting the tumor-associated antigen (TAA), cancer/testis antigen NY-ESO-1, with potential antineoplastic activity.
A carbohydrate-based galectin inhibitor, with potential antineoplastic activity. Galectin inhibitor GR-MD-02 binds to the carbohydrate-binding domain of galectins, especially galectin-3, and may result in an induction of apoptosis mediated through activation of both mitochondria and caspases. This may reduce tumor growth in galectin-overexpressing tumor cells. Galectins, often overexpressed on tumor cells, play a key role in cancer cell proliferation, apoptosis, tumor angiogenesis and evasion of immune responses.
An orally available, peripherally-acting opioid agonist, with potential visceral analgesic activity. Upon oral administration of GIC-1002, this agent binds to colonic mu and kappa opioid receptors causing analgesic effects.
A phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. PI3K inhibitor GDC-0084 specifically inhibits PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This may result in the inhibition of both cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis. Dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.
A small molecule inhibitor of cell cycle checkpoint kinase 1 (Chk1), with potential chemosensitization activity. Chk1 inhibitor GDC-0575 specifically binds to and inhibits Chk1; this may result in tumor cells bypassing Chk1-dependent cell cycle arrest in the S and G2/M phases, which permits the cells to undergo DNA repair prior to entry into mitosis. Therefore, Chk1 inhibition may sensitize tumor cells to the DNA-damaging effects of certain chemotherapeutic agents. Chk1 is an ATP-dependent serine-threonine kinase that phosphorylates cdc25 phosphatases in response to DNA damage. This results in both inhibitory tyrosine phosphorylation of cyclin-dependent kinase (CDK)-cyclin complexes and cell cycle arrest, which facilitates DNA damage repair.
An orally bioavailable inhibitor of checkpoint kinase 1 (chk1), with potential antineoplastic and chemosensitization activities. Upon oral administration, chk1 inhibitor GDC-0425 selectively binds to chk1, thereby preventing activity of chk1 and abrogating the repair of damaged DNA. This may lead to an accumulation of damaged DNA, inhibition of cell cycle arrest, and induction of apoptosis. GDC-0425 may potentiate the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapeutic agents. Chk1, an ATP-dependent serine/threonine kinase, mediates cell cycle checkpoint control, is essential for DNA repair, and plays a key role in resistance to chemotherapeutic agents.
A proprietary, antibody fragment composed of a constant (Fc) region that is engineered to bind to the tumor-associated antigen human epidermal growth factor receptor-2 (HER2), with potential antineoplastic activity. HER2-targeted antibody Fc fragment FS102 specifically binds to its HER2 epitope, and causes downregulation of HER2-mediated signaling. This leads to tumor cell apoptosis. HER2, a member of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR) superfamily, is overexpressed on the cell surface of various solid tumors.
A glycoengineered, humanized monoclonal antibody directed against the fibroblast growth factor receptor type 2b (FGFR2b), with potential antineoplastic activity. Upon administration, the anti-FGFR2 antibody FPA144 specifically binds to and inhibits FGFR2b on tumor cell surfaces, which prevents FGFR2 from binding to its ligands, FGFR2b activation and the activation of FGFR2b-mediated signal transduction pathways. The binding of FPA144 to FGFR2b protein also induces antibody-dependent cell-mediated cytotoxicity (ADCC) against FGFR2b-expressing tumor cells. This results in the inhibition of cell proliferation and the induction of cell death of FGFR2-expressing tumor cells. FGFR2b, a specific isoform of the receptor tyrosine kinase FGFR2 upregulated in many tumor cell types, is essential to tumor proliferation, differentiation and survival. Glycoengineering enhances the FPA144-mediated ADCC.
An orally available inhibitor of FMS-related tyrosine kinase 3 (FLT3, STK1, or FLK2) and the cyclin-dependent kinases 4 (CDK4) and 6 (CDK6), with potential antineoplastic activity. Upon administration, FLT3/CDK4/6 inhibitor FLX925 specifically binds to and inhibits FLT3, which interferes with the activation of FLT3-mediated signal transduction pathways and reduces cell proliferation in cancer cells that overexpress FLT3. In addition FLX925 inhibits CDK4 and 6 and prevents the phosphorylation of retinoblastoma (Rb) protein in early G1. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, which causes G1 phase cell cycle arrest, suppresses DNA synthesis and inhibits cancer cell growth. FLT3, a class III tyrosine kinase receptor, is overexpressed in a variety of cancers. Overexpression of CDK4/6, which is seen in certain types of cancer, causes cell cycle deregulation.
An inhibitor of human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon administration, FGF401 binds to and inhibits the activity of FGFR4, which leads to an inhibition of tumor cell proliferation in FGFR4-overexpressing cells. FGFR4 is a receptor tyrosine kinase upregulated in certain tumor cells and involved in tumor cell proliferation, differentiation, angiogenesis, and survival.
A systemic antifungal agent that can potentially be used in the treatment of systemic fungal infections.
An injectable, water soluble, small molecule drug conjugate (SMDC) containing a ligand specific for prostate-specific membrane antigen (PSMA), conjugated via a stable, enzyme-cleavable linker to the cytotoxic agent tubulysin B hydrazide (TubBH), with potential antineoplastic activity. Upon administration of PSMA-targeted tubulysin B-containing conjugate EC1169, the PSMA ligand specifically targets and binds to PSMA, a protein which is abundantly expressed on the surface of metastatic and hormone-refractory prostate cancer cells as well as on the neovasculature of many solid tumors. This allows for the specific delivery of TubBH to PSMA-expressing cancer cells. Upon internalization and cleavage, tubulysin B binds to tubulin and inhibits microtubule polymerization, which blocks cell division and results in G2/M phase arrest, tumor cell apoptosis and a decrease in PSMA-expressing tumor cells.
An inhibitor of the fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) pathway, with potential antineoplastic activity. Upon administration, the FGF/FGFR pathway inhibitor E7090 selectively interferes with the binding of FGF to FGFR through an as of yet not fully elucidated mechanism. This inhibits FGFR-mediated signaling and leads to both cell proliferation inhibition and cell death in FGFR-overexpressing tumor cells. FGFR is a receptor tyrosine kinase essential to tumor cell proliferation, differentiation, and survival; its expression is upregulated in many tumor cell types.
An oxidant-generating coupled-enzyme system-based, topical solution comprised of two enzymes, Aspergillus niger-derived glucose oxidase (GO) and porcine myeloperoxidase (p-MPO), as well as glucose, sodium chloride and stabilizing amino acids, with potential broad-spectrum microbicidal activity. Following direct administration of E-101 solution into the surgical incisional wound via microspray, the enzyme GO converts oxygen into hydrogen peroxide (H2O2). In turn, p-MPO catalyzes the reaction of H2O2 with hypochlorous acid (HOCl), which is formed through oxidation of the chloride ion, to generate singlet oxygen (O2*). As p-MPO binds to microorganisms, O2* is able to exert direct oxidative damage to microorganisms, resulting in potent antimicrobial activity. E-101 may act as an anti-bactericidal agent against a variety of microorganisms, including multidrug-resistant strains. This may prevent infection at the surgical site.
A synthetic CpG-rich oligonucleotide with potential immunopotentiating activity. TLR9 agonist DUK-CPG-001 binds to and activates intracellular toll-like receptor 9 (TLR9) in monocytes/macrophages, plasmacytoid dendritic cells (DCs), natural killer (NK) cells and B-cells. This initiates immune signaling pathways, activates DCs, NK cells and B-cells, and induces both the production of T-helper 1 cells (Th1) and a Th1-mediated immune response. TLR9 is a member of the TLR family, which plays a key role in both pathogen recognition and the activation of innate immunity.
An orally bioavailable, nitroimidazole-based sulfamide, carbonic anhydrase IX (CAIX) inhibitor with potential antineoplastic activity. Upon administration, CAIX inhibitor DTP348 inhibits tumor-associated CAIX, a hypoxia-inducible transmembrane glycoprotein that catalyzes the reversible reaction and rapid interconversion of carbon dioxide and water to carbonic acid, protons, and bicarbonate ions. This prevents the acidification of the tumor's extracellular microenvironment and decreases the intracellular pH. This results in increased cell death in CAIX-expressing, hypoxic tumors. In addition, DTP348, through its nitroimidazole moiety, is able to sensitize hypoxic tumor cells to irradiation. CAIX is overexpressed in various tumors and plays a key role in intra- and extracellular pH regulation, cancer cell progression, survival, migration and invasion.
A monoclonal antibody directed against the ephrin receptor A2 (EphA2), with potential antineoplastic activity. Upon administration, anti-EphA2 monoclonal antibody DS-8895a selectively binds to cells expressing the EphA2 receptor. This blocks EphA2 activation and EphA2-mediated signaling. In addition, DS-8895a may activate an immune response against EphA2-expressing tumor cells. The cell-surface receptor EphA2, a member of the ephrin family of receptor tyrosine kinases (RTKs) that are involved in mammalian development, is overexpressed by a variety of cancer cell types and plays an important role in tumor growth.
An orally available inhibitor of the receptor tyrosine kinases C-ros oncogene 1 (ROS1) and the neurotrophic tyrosine receptor kinase (NTRK) types 1, 2 and 3, with potential antineoplastic activity. Upon oral administration, DS-6051b binds to and inhibits ROS1 and the NTRK family members. This inhibition leads to a disruption of ROS1- and NTRK-mediated signaling and eventually inhibits the growth of tumor cells that are overexpressing ROS1 and/or NTRKs. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells. NTRK mutations or rearrangements play a key role in cancer progression.
An orally active and small molecule inhibitor of heat shock protein 90 (Hsp90), with potential antineoplastic activity. Upon oral administration, Hsp90 inhibitor DS-2248 specifically blocks Hsp90, which inhibits its chaperone function and promotes the proteasomal degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. This may lead to an inhibition of tumor cell proliferation. Hsp90, a chaperone complex protein upregulated in a variety of tumor cell types, regulates the folding and degradation of many oncogenic signaling proteins.
An antibody-drug conjugate (ADC) composed of MMOT0530A, a humanized immunoglobulin (Ig) G1 monoclonal antibody directed against the cell surface glycoprotein mesothelin (MSLN), and covalently linked, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of DMOT4039A binds to MSLN-expressing tumor cells and is internalized, thereby delivering MMAE intracellularly. Proteolytic cleavage releases MMAE, which then binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. MSLN, a tumor-associated antigen (TAA), is overexpressed by all mesotheliomas and a variety of other cancers, while it is minimally expressed in normal tissue.
An orally available thymidylate synthase (TS) inhibitor with potential antineoplastic activity. Upon oral administration, DFP-11207 binds to and inhibits TS. This reduces thymine nucleotide synthesis, inhibits DNA synthesis and cell division, causes DNA damage and leads to tumor cell apoptosis. TS catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP).
A deoxycytosine analog with potential antineoplastic activity. Upon administration, DFP-10917 is phosphorylated to generate its nucleotide form that functions as a deoxycytosine mimic and is incorporated into DNA in tumor cells. This causes DNA strand breaks during polymerization due to beta-elimination during the fidelity checkpoint, which results in G2/M phase-arrest and tumor cell apoptosis.
An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin (Ig) G1 monoclonal antibody against anti-endothelin B receptor (ETBR) and covalently linked to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of DEDN6526A binds to ETBR-expressing tumor cells and is internalized, thereby delivering MMAE intracellularly. Proteolytic cleavage releases MMAE, which then binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. ETBR, a G-protein coupled receptor that can activate RAF/MEK signaling, is overexpressed in a variety of tumor cell types and plays a key role in tumor cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and angiogenesis.
A lipid nanoparticle-based formulation consisting of small-interfering RNAs (siRNAs) directed against the oncogene c-Myc encapsulated in lipids with potential antineoplastic activity. Upon intravenous administration of MYC-targeting siRNA DCR-MYC, the lipid formulation promotes the uptake by tumor cells where the siRNAs moieties are subsequently released. The siRNAs bind to c-Myc mRNAs, which may result in the inhibition of translation and expression of the c-Myc protein and leads to growth inhibition for tumor cells that are overexpressing c-Myc. c-Myc, a proto-oncogene overexpressed in a variety of cancers, is involved in cellular proliferation, differentiation, and apoptosis.
An inhibitor of phosphatidylinositide 3-kinase (PI3K), raptor-mTOR (mTOR complex 1 or mTORC1) and rictor-mTOR (mTOR complex 2 or mTORC2) with potential antineoplastic activity. Upon intravenous infusion, PI3K/mTORC1/mTORC2 inhibitor DCBCI0901 binds to and inhibits PI3K as well as both mTORC1 and mTORC2, which may result in both apoptosis and a decrease in cell proliferation in tumor cells overexpressing PI3K, mTORC1, and mTORC2. Activation of the PI3K/mTOR signaling pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K.
An orally available, modified-release formulation containing the calcitriol prohormone, calcifediol (25-hydroxyvitamin D), which can potentially be used for vitamin D supplementation. Upon oral administration of the modified-release calcifediol capsule, calcifediol is slowly and gradually released in the gastrointestinal tract. Then it is taken up by the body and converted, in the kidneys, to the active form calcitriol (1,25-dihydroxyvitamin D or 1,25 D). This form increases and normalizes vitamin D plasma levels, which, in turn, regulates calcium plasma levels, and normalizes elevated parathyroid hormone (PTH) levels by suppressing both PTH synthesis, and secretion. This formulation appears to have fewer side effects than supplementation with formulations containing active 1,25 D and does not stimulate the upregulation of vitamin D 24-hydroxylase (CYP24), a cytochrome P-450 family enzyme that inactivates vitamin D.
An orally available human C-C chemokine receptor type 2 (CCR2) antagonist, with potential immunomodulating and antineoplastic activities. Upon oral administration, CCR2 antagonist CCX872-B specifically binds to CCR2 and prevents the binding its cognate endothelium-derived chemokine ligand CCL2 (monocyte chemoattractant protein-1 or MCP1). This may result in the inhibition of both CCR2 activation and CCR2-mediated signal transduction, which may inhibit inflammatory processes, angiogenesis, tumor cell migration, and tumor cell proliferation. The G-protein coupled receptor CCR2 is expressed on the surface of monocytes and macrophages, and stimulates their migration and infiltration; it plays a key role in inflammation. CCR2 is overexpressed in certain cancer cell types, where it is involved in angiogenesis, tumor cell migration and proliferation.
An orally available inhibitor of extracellular signal-regulated kinase (ERK), with potential antineoplastic activity. Upon oral administration, CC-90003 inhibits ERK activity, and prevents the activation of ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent tumor cell proliferation and survival. The mitogen-activated protein kinase (MAPK)/ERK pathway is often upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation, differentiation and survival.
An orally bioavailable inhibitor of valosin-containing protein (VCP) p97, with potential antineoplastic activity. Upon oral administration, CB-5083 specifically binds to and inhibits the activity of p97. This prevents ubiquitin-dependent protein degradation and causes cellular accumulation of poly-ubiquitinated proteins. The inhibition of endoplasmic reticulum (ER)-associated protein degradation activates the ER-dependent stress response pathway, and leads to both an induction of apoptosis and inhibition of cell proliferation in susceptible tumor cells. p97, a type II AAA ATPase, plays a key role in cellular protein homeostasis. Its overexpression in many tumor cell types is associated with increased tumor cell proliferation and survival.
A prodrug of etoposide, a semisynthetic derivative of podophyllotoxin extracted from the mandrake root Podophyllum peltatum, with potential antineoplastic activity. Upon intravenous administration of the etoposide prodrug CAP7.1, etoposide is released after enzymatic cleavage of CAP7.1 by specific carboxylesterases (CE) 1 and 2, which are upregulated in certain tumor cell types. Etoposide acts primarily in the G2 and S phases of the cell cycle. This drug binds to and inhibits topoisomerase II, an enzyme elevated in tumor cells. This results in the accumulation of double-strand DNA breaks, the inhibition of DNA replication and transcription and the induction of apoptotic cell death. The tumor-specific activation of etoposide increases its efficacy while lowering its systemic toxicity.
An orally available inhibitor of Bruton tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, BGB-3111 selectively binds to and inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B-cells that overexpress BTK. BTK, a member of the TEC family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes.
A monoclonal antibody against the tumor associated antigen (TAA) mucin-1 (MUC1), with potential antineoplastic activity. Upon administration, anti-MUC1 monoclonal antibody BTH1704 targets and binds to MUC1 expressed on the surface of tumor cells, which can potentially activate the immune system to induce an antibody-dependent cellular cytotoxicity (ADCC) against MUC1-expressing tumor cells. MUC1, a glycoprotein overexpressed on the surface of a variety of cancer cells, plays a key role in tumor cell survival and proliferation.
A dimeric fusion protein composed of the C-terminus of the domain antibody (dAb) BMS2h-572-633 targeting the CD40 ligand (CD40L or CD154) linked to a modified Fc fragment of immunoglobulin G1 (IgG1), with potential immunomodulatory activity. Upon intravenous administration, the peptide moiety of anti-CD40L antibody BMS-986004 specifically targets and binds to CD40L expressed on T-lymphocytes. This prevents the binding of CD40L to its cognate receptor CD40 expressed on B-lymphocytes, macrophages, and dendritic cells (DCs). This prevents T-cell mediated proliferation and differentiation of B-cells, and prevents the production of antibodies. By inhibiting both the production of anti-glycoprotein (GP) IIb/IIIa antibodies by B-cells and GPIIb/IIIa-dependent T-cell proliferation, BMS-986004 may prevent platelet destruction and may increase platelet counts in idiopathic thrombocytopenic purpura (ITP). The direct binding of BMS-986004 to CD40L on platelets further prevents CD40L/CD40-mediated destruction by macrophages and DCs in ITP. The modified Fc domain prevents the binding of BMS-986004 to the Fc receptor FcgammaRIIA on platelets, thereby preventing FcgammaRIIA-dependent platelet activation and anti-CD40L-induced thromboembolism. CD40L, a transmembrane protein of the tumor necrosis factor (TNF) superfamily, is primarily expressed on activated T-cells, but is also expressed on eosinophils, basophils, natural killer (NK) cells, mast cells, platelets and activated endothelial cells.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against the cell surface glycoprotein mesothelin and conjugated to an as of yet undisclosed cytotoxic drug, with potential antineoplastic activity. The monoclonal antibody moiety of anti-mesothelin ADC BMS-986148 targets and binds to the tumor associated antigen mesothelin. Upon internalization, the cytotoxic agent kills or prevents cellular proliferation of mesothelin-expressing tumor cells through an as of yet undescribed mechanism of action. Mesothelin is overexpressed by all mesotheliomas and a variety of other cancers, while it is minimally expressed in normal tissue.
An orally bioavailable, gamma secretase (GS) and pan-Notch inhibitor, with potential antineoplastic activity. Upon administration, GS/pan-Notch inhibitor BMS 986115 binds to GS and blocks the proteolytic cleavage and release of the Notch intracellular domain (NICD), which would normally follow ligand binding to the extracellular domain of the Notch receptor. This prevents both the subsequent translocation of NICD to the nucleus to form a transcription factor complex and the expression of Notch-regulated genes. This results in the induction of apoptosis and the inhibition of growth of tumor cells that overexpress Notch. Overexpression of the Notch signaling pathway plays an important role in tumor cell proliferation and survival. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains and leads to their activation.
An orally bioavailable, small-molecule gamma secretase (GS) and pan-Notch inhibitor, with potential antineoplastic activity. Upon administration, GS/pan-Notch inhibitor BMS-906024 binds to GS and blocks activation of Notch receptors, which may inhibit the proliferation of tumor cells with an overly-active Notch pathway. The integral membrane protein GS is a multi-subunit protease complex that cleaves single-pass transmembrane proteins, such as Notch receptors, at residues within their transmembrane domains that lead to their activation. Overexpression of the Notch signaling pathway has been correlated with increased tumor cell growth.
A proprietary, transdermal, hydroalcoholic gel formulation containing 17beta-estradiol, with potential antineoplastic activity. Upon topical administration, 17beta-estradiol exerts its antineoplastic effect(s) through as of yet not fully elucidated mechanism(s) of action(s). This formulation may induce feedback inhibition via the hypothalamic-pituitary-gonadal axis feedback loop, block the secretion of luteinizing hormone (LH) and prevent the release of testosterone from Leydig cells in the testes, thus suppressing testosterone secretion. In addition, 17beta-estradiol inhibits enzymes involved in steroidogenesis, thereby further inhibiting androgen production. Since testosterone is required to sustain prostate growth, reducing testosterone levels may inhibit hormone-dependent prostate cancer cell proliferation. In addition, 17beta-estradiol prevents bone loss, and suppresses andropause symptoms, such as hot flashes, which appear during androgen-deprivation therapy (ADT) where the standard of care is the use of gonadotrophin releasing hormone (GnRH) analogs. Compared to oral estrogens, the topical gel formulation lowers the risk of cardiovascular side effects.
An orally bioavailable inhibitor of the class I phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha (PIK3CA), with potential antineoplastic activity. PI3K alpha inhibitor AZD8835 selectively binds to and inhibits PIK3CA and its mutated forms, in the PI3K/Akt (protein kinase B) /mammalian target of rapamycin (mTOR) pathway. This results in both apoptosis and growth inhibition in PIK3CA-expressing tumor cells. By specifically targeting PIK3CA, this agent may be more efficacious and less toxic than pan-PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is often found in solid tumors and results in the promotion of tumor cell growth, survival, and resistance to chemo- and radio-therapy. PIK3CA, one of the most frequently mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K.
An orally available inhibitor of the epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon oral administration, AZD3759 binds to and inhibits the activity of EGFR as well as certain mutant forms of EGFR. This prevents EGFR-mediated signaling, and may lead to both induction of cell death and inhibition of tumor growth in EGFR-overexpressing cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
An orally available combination agent containing the cytidine deaminase (CDA) inhibitor E7727 and the cytidine antimetabolite decitabine, with potential antineoplastic activity. Upon oral administration of ASTX727, the CDA inhibitor E7727 binds to and inhibits CDA, an enzyme primarily found in the gastrointestinal (GI) tract and liver that catalyzes the deamination of cytidine and cytidine analogs. This prevents the breakdown of decitabine, increases its bioavailability and efficacy while decreasing GI toxicity due to the administration of lower doses of decitabine. Decitabine exerts its antineoplastic activity through the incorporation of its triphosphate form into DNA, which inhibits DNA methyltransferase and results in hypomethylation of DNA. This interferes with DNA replication and decreases tumor cell growth.
An orally available, irreversible, third-generation, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, ASP8273 covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. ASP8273 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.
An orally available, small molecule inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), with potential antineoplastic activity. Upon oral administration, ASP3026 binds to and inhibits ALK tyrosine kinase, ALK fusion proteins and ALK point mutation variants. Inhibition of ALK leads to the disruption of ALK-mediated signaling and the inhibition of cell growth in ALK-expressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. ALK is not expressed in healthy adult human tissue but ALK dysregulation and gene rearrangements are associated with a series of tumors. Additionally, ALK mutations are associated with acquired resistance to small molecule tyrosine kinase inhibitors.
An orally available non-steroidal, lyase-selective inhibitor of the steroid 17-alpha-hydroxylase/C17,20 lyase (CYP17A1 or CYP17), with potential anti-androgenic and antineoplastic activities. Upon oral administration, CYP17 lyase inhibitor ASN001 selectively binds to and inhibits the lyase activity of CYP17A1 in both the testes and adrenal glands, resulting in a significant reduction in androgen production to castrate-range levels. This may both decrease androgen-dependent growth signaling and inhibit the proliferation of androgen-dependent tumor cells. The cytochrome P450 enzyme CYP17A1, which is localized to the endoplasmic reticulum, exhibits both 17alpha-hydroxylase and 17,20-lyase activities; it plays a key role in the steroidogenic pathway. The selective inhibition of CYP17A1 lyase activity by ASN001 prevents the increased synthesis of mineralocorticoids that is normally seen with non-selective CYP17 inhibitors, which also inhibit the 17-alpha-hydroxylase activity of CYP17A1.
An antibody drug conjugate (ADC) containing a human monoclonal antibody AGS-22 targeting the cell adhesion molecule nectin-4 and conjugated to the cytotoxic agent monomethyl auristatin E (MMAE), via a proprietary enzyme-cleavable linker (AGS-22CE), with potential antineoplastic activity. The monoclonal antibody moiety of AGS-22CE selectively binds to nectin-4. After internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and induces apoptosis in nectin-4 overexpressing tumor cells. Nectin-4, a tumor associated antigen belonging to the nectin family, is overexpressed in a variety of cancers, including breast, bladder, lung and pancreatic cancer.
A personalized peptide-based cancer vaccine comprised of five to ten peptides associated with glioblastoma (GB), with potential immunomodulating and antineoplastic activities. Vaccination with synthetic GB tumor-associated peptides vaccine therapy APVAC1 stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the tumor associated peptides, and results in decreased GB growth. The peptides are derived from a glioma actively personalized vaccine consortium (GAPVAC) warehouse and are specifically selected based on the patient's expression of tumor-associated antigens.
The hydrochloride salt of a small molecule inhibitor of human metal-regulatory transcription factor 1 (MTF-1) with potential antitumor activity. MTF-1 inhibitor APTO-253 inhibits MTF-1 activity and thereby induces the expression of MTF-1 dependent tumor suppressor factor Kruppel like factor 4 (KLF4). This subsequently leads to the downregulation of cyclin D1, blocking cell cycle progression and proliferation. This agent also causes decreased expression of genes involved in tumor hypoxia and angiogenesis.
A recombinant, proprietary bispecific T-cell engagers (BiTE) antibody directed against human carcinoembryonic antigen (CEA), with potential immunostimulating and antineoplastic activities. Anti-CEA BiTE monoclonal antibody AMG211 possesses two antigen-recognition sites, one for CEA and one for the CD3 complex, a group of T cell surface glycoproteins that complex with the T cell receptor (TCR). This bispecific monoclonal antibody brings CEA-expressing tumor cells and cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) together, which may result in the CTL- and HTL-mediated cell death of CEA-expressing cells. CEA, a tumor associated antigen, is overexpressed in many cancer types, including gastrointestinal, breast, non-small cell lung, and thyroid cancers.
An immunoglobulin (Ig) G2 monoclonal antibody targeting the proangiogenic cytokines angiopoietin 1 (Ang1) and 2 (Ang2), with potential anti-angiogenic and antineoplastic activities. Upon administration, anti-angiopoietin monoclonal antibody AMG 780 binds to Ang1 and Ang2. This prevents the binding of the angiopoietin ligands to their receptor Tie2 (TEK), an endothelial cell-specific receptor tyrosine kinase. This prevents Tie2-mediated signaling and results in an inhibition of Tie2-expressing, tumor-stimulated endothelial cell proliferation, which prevents angiogenesis and inhibits tumor cell proliferation.
An orally available inhibitor of both murine double minute 2 (MDM2) and murine double minute X (MDMX), with potential antineoplastic activity. Upon oral administration, ALRN-6924 binds to both MDM2 and MDMX and interferes with their interaction with the transcriptional activation domain of the tumor suppressor protein p53. By preventing MDM2-p53 and MDMX-p53 interactions, p53 activity is restored, which leads to p53-mediated induction of tumor cell apoptosis. MDM2 and MDMX, negative regulators of p53 function, are often overexpressed in cancer cells.
A lipid nanoparticle (LNP)-based formulation consisting of small-interfering RNAs (siRNAs) directed against transthyretin (TTR) encapsulated in lipids, which has potential use in the treatment of TTR-mediated amyloidosis (ATTR). Upon intravenous administration of ALN-TTR02, the lipid formulation promotes the uptake by cells. The siRNAs bind to TTR mRNAs, which may result in the inhibition of both the translation and expression of the TTR protein. ATTR is caused by mutations in the TTR gene and results in the formation of abnormal amyloid proteins that accumulate in and cause damage to various body organs and tissues.
A proprietary formulation composed of small-interfering RNAs (siRNAs) directed against terminal complement component 5 (C5) of the complement pathway conjugated to a N-acetylgalactosamine (GalNAc) ligand, which has potential use in the treatment of complement-mediated diseases, such as paroxysmal nocturnal hemoglobinuria (PNH). Upon subcutaneous administration of ALN-CC5, the GalNAc ligand moiety specifically binds to and is taken up by the asialoglycoprotein receptor (ASGPR) expressed on hepatocytes. Inside the cell, the siRNAs bind to C5 mRNAs, which results in the inhibition of both the translation and expression of the C5 protein. This lowers plasma C5 levels, prevents C5 cleavage into pro-inflammatory components and blocks complement-mediated hemolysis. C5, a complement pathway protein, is expressed at high levels by the liver.
An antibody-drug conjugate (ADC) containing a human immunoglobulin (Ig) G2k monoclonal antibody (AGS-16C) directed against the ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3, NPP3, B10, PDNP3 CD203c, or PD-IBETA ), conjugated, via the non-cleavable maleimidocaproyl (mc) linker, to monomethyl auristatin F (MMAF), an auristatin derivative and a potent microtubule inhibitor, with potential antineoplastic activity. Upon intravenous administration of anti-ENPP3/MMAF ADC AGS-16M8F, the monoclonal antibody moiety selectively binds to ENPP3 expressed on tumor cells; upon internalization, the ADC is degraded by lysosomal proteases and MMAF is released. In turn, MMAF binds to and inhibits tubulin polymerization, which results in G2/M phase arrest and tumor cell apoptosis. While normally expressed at low levels in the proximal tubules of the kidney, the type II transmembrane glycoprotein ENPP3 is overexpressed in most renal neoplasms and some liver cancers.
An anti-CD19/anti-CD3 bispecific tetravalent antibody with potential immunostimulatory and antineoplastic activities. Anti-CD19/CD3 tetravalent antibody AFM11 possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for CD19, a tumor-associated antigen (TAA) overexpressed on the surface of B-cells. Upon bolus infusion of AFM11, this bispecific antibody binds to CD3-expressing T-cells and CD19-expressing cancer cells, thereby crosslinking CD19-expressing tumor B-cells and cytotoxic T-lymphocytes (CTLs). This may result in a potent CTL-mediated cell lysis of CD19-expressing B-lymphocytes. CD19, a B-cell specific membrane antigen, is expressed during both B-cell development and B-cell malignant growth.
A cancer vaccine containing a live-attenuated strain of the Gram-positive bacterium Listeria monocytogenes (Lm) encoding a fusion protein composed of the tumor-associated antigen (TAA) human prostate-specific antigen (PSA) fused to a fragment of the immunostimulant listeriolysin O (LLO) protein, with potential immunostimulatory and antineoplastic activities. Upon administration of the Lm-LLO-PSA vaccine ADXS31-142, the expressed LLO-PSA is processed by antigen presenting cells (APCs), presented to the immune system by both major histocompatibility complex (MHC) I and II molecules, and activates the immune system to exert both an innate and adaptive immune response involving the recruitment and activation of T-lymphocytes against PSA-expressing tumor cells as well as the inhibition of tumor-infiltrating T regulatory cells (T regs) and myeloid-derived suppressor cells (MDSCs). This eventually results in tumor cell lysis.
An orally available inhibitor of phosphatidylinositol 3-kinase (PI3K), with potential antineoplastic activity. PI3K inhibitor ACP-319 inhibits PI3K, which prevents the activation of the PI3K/AKT (protein kinase B)-mediated signaling pathway. This results in the inhibition of growth and survival of PI3K-overexpressing tumor cells. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis.
An orally bioavailable, lipid analogue and inhibitor of raptor-mammalian target of rapamycin (mTOR) (mTOR complex 1; mTORC1), rictor-mTOR (mTOR complex 2; mTORC2) and dihydrofolate reductase (DHFR) with potential antineoplastic activity. Upon oral administration, mTORC1/mTORC2/DHFR inhibitor ABTL0812 binds to and inhibits both mTORC1 and mTORC2, which may result in apoptosis and a decrease in proliferation in mTORC1/2-expressing tumor cells. mTOR is a serine/threonine kinase that is upregulated in some tumors; it plays an important role in the PI3K/Akt/mTOR signaling pathway which is often deregulated in cancer cells. In addition, ABTL0812 inhibits DHFR, an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, thereby blocking tetrahydrofolate synthesis, and resulting in both the depletion of nucleotide precursors and the inhibition of DNA, RNA and protein synthesis. This induces autophagy-induced cell death and further inhibition of cell proliferation.
A dual-specific, tetravalent immunoglobulin (Ig) G-like molecule targeting two as of yet not publicly known targets, with potential antineoplastic activity. The target-binding variable domains of two monoclonal antibodies, which are not publicly known, are combined, via linkers, to create the tetravalent, dual-targeting single agent ABT-165. Upon administration of dual variable domain immunoglobulin (DVD-Ig) ABT-165, the target-binding variable domains specifically recognize and simultaneously bind to their two antigens expressed on tumor cells. This may both prevent antigen-mediated signaling and lead to an inhibition of cellular proliferation in susceptible tumor cells. The antigen targets are overexpressed on certain tumor cell types. The DVD-Ig may have enhanced physicochemical and pharmacokinetic properties as compared to their antibody counterparts.
A pluripotent, allogeneic, tumor cell vaccine composed of irradiated tumor cells from the non-small cell lung cancer (NSCLC) cell line 1650 and the immunoadjuvant recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) (1650-G), with potential immunostimulating and antineoplastic activities. Upon administration, allogeneic cellular vaccine 1650-G may stimulate the immune system to exert a cytotoxic T-lymphocyte (CTL) immune response against tumor-associated antigens (TAAs) expressed on NSCLC cells. GM-CSF potentiates the antitumor immune response. The 1650 cell line is used as a source for TAAs.
An orally available, non-peptide gonadotropin-releasing hormone (GnRH or luteinizing hormone-releasing hormone (LHRH)) antagonist, with potential antineoplastic activity. Relugolix competitively binds to and blocks the GnRH receptor in the anterior pituitary gland, which both prevents GnRH binding to the GnRH receptor and inhibits the secretion and release of both luteinizing hormone (LH) and follicle stimulating hormone (FSH). In males, the inhibition of LH secretion prevents the release of testosterone from Leydig cells in the testes. Since testosterone is required to sustain prostate growth, reducing testosterone levels may inhibit hormone-dependent prostate cancer cell proliferation.
An orally bioavailable inhibitor of the sodium-glucose co-transporter subtype 1 (SGLT1) and 2 (SGLT2), with potential antihyperglycemic activity. Upon oral administration, sotagliflozin binds to and blocks both SGLT1 in the gastrointestinal (GI) tract and SGLT2 in the kidneys, thereby suppressing the absorption of glucose from the GI tract and the reabsorption of glucose by the proximal tubule into the bloodstream, respectively. This decreases glucose uptake and enhances the urinary excretion of glucose, which lowers and/or normalizes blood glucose levels. SGLT1 is the primary transporter responsible for glucose absorption from the GI tract. SGLT2, a transport protein exclusively expressed in the proximal renal tubules, mediates approximately 90% of renal glucose reabsorption from tubular fluid.
An orally bioavailable inhibitor of the receptor tyrosine kinases (RTKs) FMS-related tyrosine kinase 3 (FLT3, STK1, or FLK2), AXL (UFO or JTK11) and anaplastic lymphoma kinase (ALK or CD246), with potential antineoplastic activity. Gilteritinib binds to and inhibits both the wild-type and mutated forms of FLT3, AXL and ALK. This may result in an inhibition of FLT3, AXL, and ALK-mediated signal transduction pathways and reduces tumor cell proliferation in cancer cell types that overexpress these RTKs. FLT3, AXL and ALK, overexpressed or mutated in a variety of cancer cell types, play a key role in tumor cell growth and survival.
The isethionate salt form of palbociclib, an orally available cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. Palbociclib selectively inhibits cyclin-dependent kinase 4 (CDK4) and 6 (CDK6), thereby inhibiting retinoblastoma (Rb) protein phosphorylation early in the G1 phase leading to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of cell cycle progression.
The orally bioavailable, mesylate salt form of the tyrosine kinase inhibitor flumatinib, with potential antineoplastic activity. Upon administration, flumatinib inhibits the wild-type forms of Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and mast/stem cell growth factor receptor (SCFR; c-Kit) and forms of these proteins with certain point mutations. This results in the inhibition of both Bcr-Abl-, PDGFR- and c-Kit-mediated signal transduction pathways, and the proliferation of tumor cells in which these kinases are overexpressed. Bcr-Abl fusion protein is an abnormal, constitutively active enzyme expressed in Philadelphia chromosome positive chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). PDGFR, upregulated in many tumor cell types, is a receptor tyrosine kinase essential to cell migration and the development of the microvasculature. c-kit, a receptor tyrosine kinase mutated and constitutively activated in certain tumors, plays a key role in tumor cell survival, proliferation, and differentiation.
An orally available, small molecule antagonist of the tyrosine kinase transforming growth factor-beta (TGF-b) receptor type 1 (TGFBR1), with potential antineoplastic activity. Upon administration, galunisertib specifically targets and binds to the kinase domain of TGFBR1, thereby preventing the activation of TGF-b-mediated signaling pathways. This may inhibit the proliferation of TGF-b-overexpressing tumor cells. Dysregulation of the TGF-b signaling pathway is seen in a number of cancers and is associated with increased cancer cell proliferation, migration, invasion and tumor progression.
An orally bioavailable, non-steroidal estrogen naturally produced by the metabolism of the isoflavonoid daidzein by human intestinal microflora, with potential chemoprotective and estrogen receptor (ER) modulating activities. S-equol preferentially binds to and activates the beta isoform of ER in certain target tissues, while having an antagonistic effect in other tissues. This modulates the expression of ER-responsive genes in a tissue-specific manner. This agent may increase bone mineral density, affect vasomotor symptoms, and may decrease the proliferation rate of susceptible cancer cells. In addition, this agent interferes with the activity of enzymes involved in steroid biosynthesis. S-equol inhibits dihydrotestosterone (DHT) production and may inhibit the proliferation of androgen-driven prostate cancer. S-equol is the biologically active enantiomer while R-equol is essentially inactive and has a weak affinity for alpha-ER.
Pre-B acute lymphoblastic leukemia that occurs during childhood.
Pre-B acute lymphoblastic leukemia that occurs during adulthood.
Side effects of cancer treatment occurring a long time after the treatment was completed.
A rare endometrial carcinoma characterized by the presence of both malignant glandular and malignant squamous cellular components.
A nutritional supplement containing the phytochemical polyphenol, ellagic acid, and an extract of Annona muricata, with potential chemopreventive activity. Although the exact mechanism of action for ellagic acid has yet to be fully elucidated, this agent acts as an anti-oxidant and reduces oxidative stress. This agent also appears to protect the body against certain carcinogens, either through preventing DNA binding or by increasing the rate of their metabolism and deactivation. Certain extracts of Annona muricata, a member of the custard apple plants and belonging to the Annonaceae family, may have antiviral activity, potential targets include human papilloma virus (HPV), and may be cytotoxic against various types of cancer cells.
An indication as to whether repeat revascularization of a lesion occurred.
A human agonistic monoclonal antibody (MoAb) specific for CD27, with potential immunostimulating and antineoplastic activity. Upon administration of varlilumab, this MoAb binds to CD27 and may potentiate the immune response by increasing the cytotoxic T-lymphocyte (CTL) response against CD27-expressing tumor cells. This may lead to growth inhibition of CD27-expressing tumor cells. In addition, this agent may increase the proliferation and activation of antigen-specific T lymphocytes upon co-administration of TAA-containing vaccines, such as dendritic cell vaccines. CD27, a co-stimulatory molecule and member of the tumor necrosis factor family overexpressed in certain tumor cell types, is constitutively expressed on mature T-lymphocytes, memory B cells and natural killer cells and plays an important role in NK cell mediated cytolytic activity and T and B lymphocyte proliferation and activation.
A preparation of genetically modified autologous T-cells transduced with a replication incompetent, self-inactivating lentiviral vector expressing a hinge-optimized, chimeric antigen receptor (CAR), containing a CD28 co-stimulatory signaling domain fused to CD3 zeta, the single-chain variable fragment of CD123 (Interleukin-3 receptor alpha chain or IL3RA) antigen, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous CD123CAR-CD28-CD3zeta-EGFRt-expressing T Lymphocytes are directed to and induce selective toxicity in CD123-expressing tumor cells. CD123 is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with increased leukemic cell proliferation and aggressiveness. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates detection of the administered T-cells in vivo and can promote elimination of those cells following a cetuximab-induced antibody-dependent cellular cytotoxicity response. The costimulatory signaling domain enhances both proliferation of T-cells and antitumor activity. Hinge optimization prevents recognition of the CAR by Fc receptors (FcRs).
A bilateral visual field defect on opposite sides of the visual space of each eye (right or left).
A focal intestinal perforation without a definite cause, commonly located in the terminal ileum, lacking the transmural inflammation and/or pneumatosis typically seen in necrotizing enterocolitis.
Infection in the first month of life caused by the Herpes simplex virus.
A solution containing sodium chloride that can be used to cleanse the nasal passages. Upon nasal irrigation, the saline washes out thick or dry mucus, and irritants, such as pollen, dust particles, pollutants and bacteria, from the nasal cavities. This reduces nasal blockage, improves nasal airflow and helps keep nasal passages clean and clear, which decreases the risk of irritation and inflammation. The saline solution also moisturizes and soothes irritated mucus membranes.
A finding of oligoastrocytoma in childhood that has not been treated.
A benign or malignant, circumscribed or diffuse neoplasm that arises from melanocytes in the leptomeninges and occurs during adulthood.
An indication or description of a record that is considered to be the accepted and final evaluation.
Infection of an infant from seven days to three months of life caused by Group B Streptococcus (Streptococcus agalactiae).
An autoinflammatory disease caused by mutations in the NLRP12 gene. It is characterized by periodic fevers beginning in the first year of life that are triggered by cold exposure. Episodes occur more than once per month.
Slowly progressive systemic mastocytosis with uncertain prognosis. It is characterized by organomegaly and absence of aggressive disease.
A rare genetic deficiency characterized by mutations in the SHOX gene and reduced expression or function of the SHOX protein. It results in the disruption of normal bone development and growth starting before birth. It manifests with skeletal abnormalities and short stature.
A type of skin cancer on or under the skin that has spread from the primary tumor through the lymph system and is not more than 2 centimeters away from the original tumor.
Meconium staining of the fetal membrane.
An indication of whether the subject has died.
Bleeding within the subarachnoid space occurring during labor and/or delivery.
The development of secondary sexual characteristics contrary to pre-pubertal phenotype (feminization in boys; virilization in girls).
Growth hormone deficiency the cause of which is present at birth.
An injury sustained during the birthing process in which the continuity is broken in the skull.
A pineal parenchymal cell neoplasm that occurs during childhood.
A rare malignant small intestinal neoplasm that occurs during childhood.
Gliomatosis cerebri that occurs during childhood.
A rare breast carcinoma that occurs during childhood.
Reduced or abnormal sight in the central visual field.
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis (excludes peritoneal metastasis). (AJCC 7th Ed.)
Stage IIIA includes: For squamous cell carcinoma: (T1-2, N2, M0, Any G, Tumor location: Any); (T3, N1, M0, Any G, Tumor location: Any); (T4a, N0, M0, Any G, Tumor location: Any). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T4a: Resectable tumor invading pleura, pericardium, or diaphragm. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. For adenocarcinoma: (T1-2, N2, M0, Any G); (T3, N1, M0, Any G); (T4a, N0, M0, Any G). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. T4a: Resectable tumor invading pleura, pericardium, or diaphragm. N0: No regional lymph node metastasis. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Increased production of androgens by the ovaries.
An orally bioavailable formulation of azacitidine, a pyrimidine nucleoside analogue of cytidine, with antineoplastic activity. Upon oral administration, azacitidine is taken up by cells and metabolized to 5-azadeoxycitidine triphosphate. The incorporation of 5-azadeoxycitidine triphosphate into DNA reversibly inhibits DNA methyltransferase, and blocks DNA methylation. Hypomethylation of DNA by azacitidine may re-activate tumor suppressor genes previously silenced by hypermethylation, resulting in an antitumor effect. In addition, the incorporation of 5-azacitidine triphosphate into RNA disrupts normal RNA function and impairs tRNA (cytosine-5)-methyltransferase activity, resulting in an inhibition of RNA and protein synthesis.
A cytogenetic abnormality that refers to the translocation of an FGFR family gene to a new chromosomal location.
Specifies whether the pharmacokinetic concentration result values should be excluded from the statistical analysis.
A response indicating that something occurs with a bit less frequency or intensity as previously.
The permanent failure of bone to heal, commonly due to a fracture or an osteotomy.
Idiopathic tall stature in a child when neither parent is tall in stature.
The reemergence of protoplasmic astrocytoma in childhood after a period of remission.
A non-infectious, recombinant, nonavalent vaccine prepared from highly purified virus-like particles (VLPs) comprised of the major capsid (L1) proteins from human papillomavirus (HPV) types 6, 11, 16, 18, 31, 33, 45, 52, and 58, with active immunizing activity. Upon administration, the recombinant HPV nonavalent vaccine activates the immune system to produce antibodies against the 9 HPV types. This protects against HPV infection and HPV-related cancers. Altogether, HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 account for the majority of the HPV types that cause cervical, vulvar, vaginal and anal cancers.
Early hepatocellular carcinoma. Patients are candidates for radical therapies (resection, liver transplantation, or percutaneous treatments). (HPB (Oxford) 2005; 7(1):35-41)
A translocation between chromosome 9 and chromosome 22 that may be associated with Philadelphia chromosome and increased susceptibility to several types of leukemia.
A cytogenetic abnormality that involves a translocation between chromosomes 8 and 21.
A cytogenetic abnormality that refers to the translocation involving the genes CIC (capicua transcriptional suppressor) on chromosome 19 and DUX4 (double homeobox 4) on chromosome 4 resulting in CIC-DUX4 fusion.
A chromosomal translocation involving chromosome 1 and chromosome 14.
A chromosomal translocation involving chromosome 14 and chromosome 20.
A cytogenetic abnormality that refers to the translocation involving the genes CIC (capicua transcriptional suppressor) on chromosome 19 and DUX4L (double homeobox 4-like) on chromosome 10 resulting in CIC-DUX4L fusion.
A chromosomal inversion that involves chromosome 16.
A chromosomal inversion that involves chromosome 16. It is associated with the development of acute myeloid leukemia CBFB-MYH11, acute myelomonocytic leukemia with abnormal eosinophils, and granulocytic sarcoma.
A therapeutic cancer vaccine containing a truncated, synthetic peptide mimic of the human angiogenic activator vascular endothelial growth factor (VEGF), consisting of 79 amino acids (amino acids 26-104 of VEGF), and emulsified in the immunoadjuvant RFASE, with potential immunostimulatory and antitumor activities. Upon intramuscular vaccination, the hVEGF26-104 moiety of hVEGF26-104/RFASE acts as an antigen and induces an immune response against VEGF, which results in anti-VEGF antibody binding to and neutralization of endogenous VEGF. This prevents the binding of endogenous VEGF to the VEGF receptor (VEGFR) and blocks VEGFR-mediated endothelial cell signaling, resulting in an inhibition of both angiogenesis and tumor cell proliferation. VEGF plays a key role in angiogenesis, tumor cell proliferation and invasion. RFASE, which belongs to the group of sulpholipopolysaccharides (SLPs), is a synthetic polysaccharide covalently coupled to lipid groups and sulphate groups, and is able to induce a strong humoral immune response upon antigen administration.
An injectable, colloidal formulation of the radioisotope yttrium Y 90, with potential antineoplastic activity. When injected into the tumor, the yttrium Y 90 colloid selectively delivers a cytotoxic dose of beta-emitting yttrium Y 90 to the tumor site, which may result in both tumor cell death and tumor regression.
A finding of a worsening decrease in blood supply to the vital organs.
Focal areas of necrosis, with or without cysts, and diffuse areas of white matter dysmaturation with maturation arrest of the pre-oligodendroglia cells, located in the cerebral white matter.
A description of the diagnostic criterion that the subject fulfilled in order to establish a medical diagnosis.
A finding of rapid weight gain due to fluid retention.
A cell-based cancer vaccine composed of donor-derived dendritic cells (DCs) loaded with three, human leukocyte antigen A2 (HLA-A2)-binding peptides derived from the human tumor-associated antigen (TAA) Wilms tumor protein 1 (WT1), with potential immunomodulating and antineoplastic activities. Upon vaccination, WT1 peptide-loaded allogeneic DC vaccine exposes the immune system to WT1-derived peptides and may stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against WT1-expressing cancer cells, which could result in tumor cell lysis. WT1, a transcription factor, is overexpressed in leukemic cells and in various solid tumors, and only minimally in normal tissues; its expression often correlates with disease progression and poor prognosis. HLA-A2 is an MHC class I molecule that presents antigenic peptides to CD8+ T-cells; restricting the peptides to those epitopes that bind most efficiently to HLA-A2 may improve antigenic peptide immunogenicity.
The level of awareness of an organism during a vital signs assessment.
An indication as to whether repeat revascularization of an artery containing a lesion occurred.
An indication as to whether an artery is patent (free of TLR or restenosis) following intervention.
An indication as to whether vessel occlusion occurred 48 hours after a coronary artery bypass graft procedure
An indication as to whether vessel failure occurred.
Ischemic or hemorrhagic stroke resulting from cerebral venous thrombosis.
A fetal blood vessel in the placental membranes that extends from the cord insertion to the chorionic plate.
A change in the nucleotide sequence of the VHL gene.
A focus of thrombus adhered to the wall of an uteroplacental vessel.
The degeneration of an uteroplacental vessel with or without medial foamy macrophages.
Extravasation of urine outside the urinary collecting system.
A cream containing urea and the alpha hydroxy acid lactic acid, with potential keratolytic and hydrating activities. Upon topical application to the affected areas, the urea/lactic acid-based topical cream breaks down keratin and moisturizes the skin.
The weight of the placenta after delivery, with membranes intact and some length of the umbilical cord attached, to the nearest gram, before draining the blood from the specimen.
A finding of metastatic squamous cell carcinoma to neck with occult primary that has not been treated.
A finding of hematopoietic or lymphoid cell neoplasm that has not been treated.
A finding of subependymal giant cell astrocytoma in childhood that has not been treated.
A finding of childhood rhabdomyosarcoma that has not been treated.
A finding of protoplasmic astrocytoma in childhood that has not been treated.
A finding of pleomorphic xanthoastrocytoma in childhood that has not been treated.
A finding of pilomyxoid astrocytoma in childhood that has not been treated.
A finding of pilocytic astrocytoma in childhood that has not been treated.
A finding of oligodendroglioma in childhood that has not been treated.
A finding of myeloid neoplasm in childhood that has not been treated.
A finding of childhood low grade astrocytic tumor that has not been treated.
A finding of childhood high grade astrocytic tumor that has not been treated.
A finding of gliosarcoma in childhood that has not been treated.
A finding of gliomatosis cerebri in childhood that has not been treated.
A finding of glioblastoma in childhood that has not been treated.
A finding of giant cell glioblastoma in childhood that has not been treated.
A finding of gemistocytic astrocytoma in childhood that has not been treated.
A finding of fibrillary astrocytoma in childhood that has not been treated.
A finding of diffuse astrocytoma in childhood that has not been treated.
A finding of cerebral astrocytoma in childhood that has not been treated.
A finding of anaplastic oligodendroglioma in childhood that has not been treated.
A finding of anaplastic oligoastrocytoma in childhood that has not been treated.
A finding of anaplastic astrocytoma in childhood that has not been treated.
A finding of central nervous system neoplasm that has not been treated.
The typical uniform coloring of the placental parenchyma irrespective of gestational age.
A category of juvenile idiopathic arthritis that does not fulfill any single category or has criteria for more than one category.
An electrocardiographic finding of a cardiac rhythm whose mechanism cannot be determined from the ECG. (CDISC)
A neutrophilic infiltrate arising from fetal vessels of the umbilical cord into the umbilical vessel wall and oriented towards the amniotic cavity.
Change in umbilical cord color resulting from postmortem changes. It indicates fetal death occurred at least 6 hours prior to delivery.
The longest measured width of the umbilical cord.
An orally bioavailable monoclonal antibody against CXC Chemokine Receptor 4 (CXCR4) with potential antineoplastic activity. Ulocuplumab binds to the chemokine receptor CXCR4, preventing the binding of stromal derived factor-1 (SDF-1) to the CXCR4 receptor and subsequent receptor activation, which may result in decreased tumor cell proliferation and migration. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types.
A nanodispersion containing the benzoquinone ubidecarenone (coenzyme Q10), with potential protective, antioxidant and antineoplastic activities. Upon administration, ubidecarenone nanodispersion BPM31510 modulates tumor cell metabolism and causes an anti-Warburg effect by inducing a shift from lactate dependency towards mitochondrial oxidative phosphorylation, and induces tumor cell apoptosis. This inhibits tumor cell proliferation. BPM 31510 also induces the activation and maturation of T-lymphocytes, and changes the surface expression of certain immune checkpoint modulators. In addition, as an antioxidant, ubidecarenone protects against cell damage, by preventing both the peroxidation of lipid membranes and the oxidation of LDL-cholesterol. Ubidecarenone is an essential coenzyme for mitochondrial enzyme complexes involved in oxidative phosphorylation and the production of adenosine triphosphate (ATP).
The outcome of the tumor results assessment as originally received or collected.
The standard character or string for representation and reporting of tumor results data.
An indication or description of a record that is considered to be the accepted and final evaluation for the tumor result.
The outcome of the tumor identification assessment as originally received or collected.
An indication or description of a record that is considered to be the accepted and final evaluation for the tumor identification.
The outcome of the tumor findings assessment as originally received or collected.
An indication or description of a correlation between death and a tumor finding.
A finding obtained using FDG-PET imaging demonstrating the disappearance of metabolic tumor activity in target and non-target lesions, marked by a decrease in tumor standardized uptake value to the level of surrounding normal tissue.
The weight of the trimmed placenta to the nearest gram, with membranes severed at the disc edge and the umbilical cord cut to within 1 cm of insertion, after draining the blood from the specimen.
A disorder of decreased production of parathyroid hormone by the parathyroid gland in a newborn. It is due to maternal hyperparathyroidism. It may be characterized by hypocalcemic seizures in the first weeks of life.
A condition in a newborn characterized by a temporary decrease in right ventricular and/or left ventricular output.
Tics that are secondary to an identifiable cause.
A cancer vaccine containing autologous dendritic cells (DCs) that are loaded with total tumor RNA (TTRNA) from a specific tumor, with potential immunostimulatory and antineoplastic activities. Upon administration, TTRNA-loaded DC vaccine may elicit a highly specific cytotoxic T-cell (CTL) response against the tumor-associated antigens (TAAs) encoded by the TTRNA.
A topical formulation containing the naturally-derived biomaterial keratin that has wound repair promoting, hemostatic, moisturizing and potential radioprotective activities. Upon topical application to an injured site, keratin adheres to the injured tissue, and forms an extracellular matrix that mimics the structure and function of the native tissue. This exogenous extracellular matrix is able to absorb fluid, accelerate thrombus formation through beta1 integrin-mediated platelet adhesion and forms a physical seal on the wound. This facilitates tissue regeneration by promoting cellular proliferation and migration, reducing pro-inflammatory cytokine and chemokine expression and altering the expression of extracellular matrix components and adhesion molecules. Altogether, this promotes wound healing and provides protection from damage due to thermal or radiation exposure. Keratin is an essential component in nails, hair and skin.
Disruption of the tentorium cerebelli incurred during delivery.
An orally bioavailable granular formulation composed of the fluoropyrimidine antagonist tegafur combined with two modulators of 5-fluorouracil (5-FU) activity, gimeracil and oteracil potassium, and the folic acid derivative leucovorin calcium, with potential antineoplastic activity. Tegafur is a prodrug of 5-fluorouracil (5-FU), an antimetabolite that is further metabolized to 5-fluoro-2'-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits thymidylate synthase, DNA synthesis and cell division; FUTP competes with uridine triphosphate (UTP), thus inhibiting RNA and protein synthesis. Gimeracil is a reversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the liver enzyme responsible for rapid catabolism of 5-FU into inactive metabolites. Oteracil potassium preferentially localizes in the gut and inhibits the enzyme orotate phosphoribosyl-transferase (OPRT), which converts tegafur to 5-FU. This decreases the amount of 5-FU in the gut and prevents activated 5-FU-related gastrointestinal (GI) toxicity. Leucovorin calcium, an active metabolite of folic acid, counteracts the toxic effects of 5-FU, thereby 'rescuing' the patient while permitting the antitumor activity of 5-FU.
A radioconjugate composed of an urea-based human prostate-specific membrane antigen (PSMA)-targeting ligand, conjugated to the gamma-emitting radioisotope technetium Tc 99m, with potential use as a tracer for PSMA-expressing tumors using single photon emission computed tomography/computed tomography (SPECT/CT). Upon intravenous administration of the technetium Tc 99m trofolastat, the trofolastat moiety targets and binds to PSMA-expressing tumor cells. Upon internalization, PSMA-expressing tumor cells can be detected during SPECT/CT imaging. PSMA, a tumor-associated antigen and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells.
A change in the nucleotide sequence of the TSC2 gene.
A change in the nucleotide sequence of the TSC1 gene.
A change in the nucleotide sequence of the TP53 gene.
An indication as to whether the subject had symptoms related to the clinical event of interest.
An electrocardiographic recording that demonstrates two sequential premature atrial complexes.
An orally bioavailable, small molecule inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3, and the fibroblast growth factor receptor type 1 (FGFR1), with potential antineoplastic and anti-angiogenic activities. Upon oral administration, sulfatinib binds to and inhibits VEGFRs and FGFR1 thereby inhibiting VEGFR- and FGFR1-mediated signal transduction pathways. This leads to a reduction of angiogenesis and tumor cell proliferation in VEGFR/FGFR1-overexpressing tumor cells. Expression of VEGFRs and FGFR1 may be upregulated in a variety of tumor cell types.
The outcome of the subject status assessment as originally received or collected.
Bleeding in the potential space between the skull periosteum and the scalp galea aponeurosis of a newborn infant due to shearing forces on the tentorium and deep venous system during labor and delivery.
Bleeding within the subdural space occurring during labor and/or delivery.
A collection of blood between the renal capsule and the renal parenchyma.
A focus of necrotic placental parenchyma with moderate hyalinization and fibrosis with partial absence of the necrotic chorionic villi, which is frequently 3-5 days of duration.
A focus of maternal thrombus within the placental intervillous space, often with peripheral villous compression, which is 3-5 days in age.
Disruption of the sternocleidomastoid muscle incurred during delivery.
The formation of a blood clot of a vessel or heart chamber after and due to the placement of a stent.
Stage IIIC includes: (T3c, N0, M0); (Any T, N1, M0). T3c: Peritoneal tumor beyond pelvis more than 2cm in greatest dimension and/or regional lymph node metastasis. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IIIC includes: For squamous cell carcinoma: (T4a, N1-2, M0, Any G, Tumor location: Any); (T4b, Any N, M0, Any G, Tumor location: Any); (Any T, N3, M0, Any G, Tumor location: Any). T4a: Resectable tumor invading pleura, pericardium, or diaphragm. T4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. For adenocarcinoma: (T4a, N1-2, M0, Any G); (T4b, Any N, M0, Any G); (Any T, N3, M0, Any G). T4a: Resectable tumor invading pleura, pericardium, or diaphragm. T4b: Unresectable tumor invading other adjacent structures, such as aorta, vertebral body, trachea, etc. N1: Metastasis in 1-2 regional lymph nodes. N2: Metastasis in 3-6 regional lymph nodes. N3: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Macroscopic peritoneal tumor beyond pelvis 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IIIB includes: For squamous cell carcinoma: T3, N2, M0, Any G, Tumor location: Any. T3: Tumor invades adventitia. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. For adenocarcinoma: T3, N2, M0, Any G. T3: Tumor invades adventitia. N2: Metastasis in 3-6 regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIIA includes: T3a, N0, M0. T3a: Microscopic peritoneal tumor beyond pelvis (no macroscopic tumor). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th Ed.)
Stage III includes: T3, N0, M0. T3: Microscopically confirmed peritoneal tumor outside pelvis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th Ed.)
Stage IB includes: For squamous cell carcinoma: (T1, N0, M0, G2-3, Tumor location: Any); (T2-3, N0, M0, G1, GX, Tumor location: Lower, X). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. G2: Moderately differentiated. G3: Poorly differentiated. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. For adenocarcinoma: (T1, N0, M0, G3); (T2, N0, M0, G1-2, GX). T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. G2: Moderately differentiated. G3: Poorly differentiated. GX: Grade cannot be assessed-stage grouping as G1. (AJCC 7th ed.)
Stage IA includes: For squamous cell carcinoma: T1, N0, M0, G1, GX, Tumor location: Any. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. For adenocarcinoma: T1, N0, M0, G1-2, X. T1: Tumor invades lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. G2: Moderately differentiated. GX: Grade cannot be assessed-stage grouping as G1. (AJCC 7th ed.)
An ointment containing an inhibitor for both Src tyrosine kinase and tubulin polymerization, with potential antineoplastic activity. Unlike other Src kinase inhibitors which bind to the ATP-binding site, Src kinase inhibitor KX2-391 binds to the peptide substrate binding site of Src kinase, upon topical application. This inhibits both downstream signaling and the proliferation of tumor cells overexpressing Src. Src tyrosine kinase, a non-receptor tyrosine kinase upregulated in many tumor cell types, plays an important role in tumor cell proliferation, motility, invasiveness and survival. KX2-391 also binds to tubulin heterodimers and inhibits microtubule polymerization, which disrupts microtubule formation and mitosis, leading to further inhibition of cell proliferation. In addition, KX2-391 inhibits T-cell migration.
Disruption of the spleen incurred during delivery.
Showing some signs of deterioration or decline.
An oral preparation containing sodium sulfate, potassium sulfate and magnesium sulfate, with osmotic laxative activity. Upon oral administration of the sodium sulfate/potassium sulfate/magnesium sulfate-based laxative, this osmotic laxative promotes the retention of water in the bowel. This increases the water content of stool, which results in increased gastrointestinal motility and facilitates the evacuation of colonic contents. This results in a complete cleansing of the colon.
A condition in which a child who was born small for gestational age, fails to achieve a linear growth rate sufficient to restore height to within the normal range for the reference population.
Birth weight greater than two standard deviations below the mean for the reference population of the same sex and gestational age.
Birth weight and length greater than two standard deviations below the mean for the reference population of the same sex and gestational age.
Birth length greater than two standard deviations below the mean for the reference population of the same sex and gestational age.
Clinical course characterized by slow progression without signs of aggressive disease.
Weakness of extraocular muscle function as a result of inadequate securing of the muscle to the sclera during strabismus surgery.
The outcome of the skin response assessment as originally received or collected.
The standard character or string for representation and reporting of skin response data.
Any skin care product containing humectants, emollients and emulsifiers with moisturizing activity. These products increase the skin's hydration and are used to soften and protect dry skin.
The space that occupies the distance between the shortest free edge of the fetal membranes and the disc edge.
A tic that involves one muscle or muscle group, or non-word sounds.
A traditional Chinese medicine comprising different herbs that may be used for a variety of medical purposes. Shu Yu Wan contains the following herbs: Da Zao (Fructus Jujubae), Shu Yu (Radix Dioscoreae Quinquelobae), Gan Cao (Radix Glycyrrhizae Uralensis), Shu Di Huang (Radix Rehmanniae Glutinosae Praeparata), Dang Gui (Radix Angelicae Sinensis), Shen Qu (Massa Medica Fermentata), Gui Zhi (Ramulus Cinnamomi Cassiae), Da Dou Juan (Semen Glycines Germinatum), E Jiao (Gelatinum Corii Asini), Ren Shen (Radix Ginseng), Bai Zhu (Rhizoma Atractylodis Macrocephalae), Fu Ling (Sclerotium Poriae Cocos), Chuan Xiong (Radix Ligustici Wallichii), Bai Shao Yao (Radix Paeoniae Lactiflorae), Mai Men Dong (Tuber Ophiopogonis Japonici), Chai Hu (Radix Bupleuri), Fang Feng (Radix Ledebouriellae Divaricatae), Jie Geng (Radix Platycodi Grandiflori), Xing Ren (Semen Pruni Armeniacae), Bai Lian (Radix Ampelopsis Japonicae) and Sheng Jiang (Rhizoma Zingiberis Officinalis Recens). This formula may be used to relieve chemotherapeutic side effects or cancer-related symptoms.
The length, in cm, of the shortest axis of the chorionic disc.
An electrocardiographic finding of a short or absent ST segment, resulting in a decreased QT interval, without changes in T wave morphology; this may be observed in hypercalcemia. (CDISC)
A non-Hodgkin lymphoma that has metastasized to the central nervous system following the initial presentation in another nodal or extranodal site.
A Hodgkin lymphoma that has metastasized to the central nervous system following the initial presentation in another nodal or extranodal site.
A pathologic communication between the skin and the dural space that is located 5-25 mm from the anal verge.
A fetal blood vessel in the placental membranes that appears torn upon gross inspection of the placenta.
An ophthalmoscopic finding that refers to retinopathy of prematurity.
Any new or worsening ST or T wave changes present in two or more contiguous leads that occur when a patient is experiencing neither physical nor chemical stressors.
The outcome of the reproductive system findings assessment as originally received or collected.
An indication or description that reproductive system findings data is a derived value.
An indication or description that reproductive system findings data is a baseline value.
Thrombus formation within the arterial or venous system of a donor kidney post transplantation.
A focus of necrotic placental parenchyma with marked hyalinization and fibrosis with complete absence of the necrotic chorionic villi, which is frequently more than 7 days of duration.
A focus of maternal thrombus within the placental intervillous space, often with peripheral villous compression, which is at least 5-7 days in age.
Hodgkin lymphoma that occurs during childhood and is resistant to treatment.
The reemergence of primary peritoneal carcinoma after a period of remission.
The reemergence of pancreatic neuroendocrine carcinoma after a period of remission.
The reemergence of oropharyngeal undifferentiated carcinoma after a period of remission.
The reemergence of olfactory neuroblastoma after a period of remission.
The reemergence of malignant extragonadal non-seminomatous germ cell tumor after a period of remission.
The reemergence of malignant extragonadal germ cell tumor after a period of remission.
The reemergence of inverted Schneiderian papilloma after a period of remission.
The reemergence of fallopian tube carcinoma after a period of remission.
The reemergence of extragonadal seminoma after a period of remission.
The reemergence of combined thymic epithelial neoplasm after a period of remission.
The reemergence of subependymal giant cell astrocytoma in childhood after a period of remission.
The reemergence of renal neoplasm in childhood after a period of remission.
The reemergence of pleomorphic xanthoastrocytoma in childhood after a period of remission.
The reemergence of pilomyxoid astrocytoma in childhood after a period of remission.
The reemergence of pilocytic astrocytoma in childhood after a period of remission.
The reemergence of oligodendroglioma in childhood after a period of remission.
The reemergence of oligoastrocytoma in childhood after a period of remission.
The reemergence of non-Hodgkin lymphoma in childhood after a period of remission.
The reemergence of gliosarcoma in childhood after a period of remission.
The reemergence of gliomatosis cerebri in childhood after a period of remission.
The reemergence of glioblastoma in childhood after a period of remission.
The reemergence of giant cell glioblastoma in childhood after a period of remission.
The reemergence of gemistocytic astrocytoma in childhood after a period of remission.
The reemergence of fibrillary astrocytoma in childhood after a period of remission.
The reemergence of diffuse astrocytoma in childhood after a period of remission.
The reemergence of childhood central nervous system embryonal neoplasm after a period of remission.
The reemergence of a childhood astrocytic tumor after a period of remission.
The reemergence of anaplastic oligodendroglioma in childhood after a period of remission.
The reemergence of anaplastic oligoastrocytoma in childhood after a period of remission.
The reemergence of anaplastic large cell lymphoma in childhood after a period of remission.
The reemergence of anaplastic astrocytoma in childhood after a period of remission.
The reemergence of borderline ovarian epithelial tumor after a period of remission.
An adenovirus type 5 (Ad5) encoding human tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), with potential apoptosis-inducing and antineoplastic activities. Upon administration of recombinant Ad5 encoding TRAIL, the adenovirus selectively infects tumor cells and expresses TRAIL. The virally expressed TRAIL binds to and activates its receptors TRAIL receptor-1 (TRAIL-R1, death receptor 4, DR4) and TRAIL receptor-2 (TRAIL-R2, death receptor 5, DR5), which subsequently activate caspases and induce apoptosis in TRAIL-R1/R2-expressing tumor cells. The pro-apoptotic cell surface receptors TRAIL-R1 and -R2, members of the TNF receptor family, are overexpressed by a variety of cancer cell types.
A response indicating that something occurs with less frequency or intensity as previously.
An indication as to whether the device was set to correct for random noise generated by deflected positrons.
Autologous, genetically engineered T-lymphocytes that have been electroporated with an mRNA encoding for an anti-CD19 chimeric antigen receptor (CAR) consisting of an anti-CD19 single chain variable fragment (scFv) coupled to the co-stimulatory signaling domain of 4-1BB (CD137) and the zeta chain of the T-cell receptor CD3 complex (CD3-zeta), with potential immunomodulating and antineoplastic activities. Upon transfusion, the RNA electroporated CD19CAR-CD3zeta-4-1BB-expressing autologous T-lymphocytes attach to cancer cells expressing CD19. This induces selective toxicity against CD19-expressing tumor cells and causes tumor cell lysis. The 4-1BB co-stimulatory molecule signaling domain enhances T-cell activation and signaling after recognition of CD19. CD19 antigen is a B-cell specific cell surface antigen, which is expressed in all B-cell lineage malignancies.
Imaging findings consistent with increased intravascular blood volume in the lungs.
A carcinoma that arises from the proximal part of the urethra.
A dendritic cell (DC)-based cancer vaccine composed of autologous dendritic cells (DCs) activated with a prostate tumor cell lysate containing tumor-associated antigens (TAAs) with potential immunostimulatory and antineoplastic activities. Upon administration, the prostate tumor antigen-activated autologous DC vaccine may stimulate an anti-tumoral cytotoxic T-lymphocyte (CTL) response against prostate cancer cells expressing prostate tumor cell-specific antigens, which may result in prostate tumor cell lysis.
Perception of the orientation of the body in space, manifesting as a sensation of floating, flying, in the absence of a corresponding stimulus.
An indication as to whether the procedure is considered successful.
An indication or description of a procedure occurrence.
The separation of the vitreous from the retina.
A fetus of 16-20 weeks gestational age that shows signs of life at birth but dies after delivery.
An abnormal accumulation of cerebrospinal fluid within the ventricles of the brain that occurs as a consequence of a central nervous system inflammation.
An abnormal accumulation of cerebrospinal fluid within the ventricles of the brain that occurs as a later sequela of an intraventricular or subarachnoid hemorrhage.
Three or more foci of two or more placental terminal villi showing karyorrhexis of fetal cells with preservation of the surrounding trophoblast. The villi may also show stromal hypercellularity and mineralization, and can either be hypovascular or only exhibit capillary degenerative changes. Entrapped red blood cells and red blood cell fragments are often seen.
Extravascular blood in the chorionic villi.
Increased density of placental villous stroma, often with decreased capillarization compared to what would be expected for gestational age.
Placental villous histology not typical of gestational age, with developmentally abnormal features.
The deposition of iron and/or calcium within the supporting tissues of the placenta.
Macroscopically identifiable placental parenchymal abnormality.
The presence of a small clot attached to the epithelial surface of a placental villus.
The measured or estimated height of the placental disc perpendicular to the chorionic and basal plates.
A description of the physical examination evidence of heart failure that can be classified as new or worsening.
A condition characterized by reduced or absent movement of the ipsilateral diaphragm as a consequence of an injury to the phrenic nerve or its origin in cervical roots 3 through 5 sustained during the birthing process.
An indication or description that pharmacokinetic concentration data is a baseline value.
A lingering, usually unpleasant, taste without the associated stimulus.
A polyepitope DNA vaccine composed of a DNA plasmid encoding multiple, highly immunogenic tumor associated antigens (TAAs) that are specifically selected after genome profiling of the patient's breast cancer cells, with potential immunostimulatory and antineoplastic activities. Upon intramuscular administration and electroporation of the personalized polyepitope plasmid DNA breast cancer vaccine, the expressed TAAs induce cytotoxic T-lymphocyte (CTL) immune responses against tumor cells expressing the TAAs.
Oligoarticular juvenile idiopathic arthritis that never involves more than four separate joints after six months.
Persistent Mullerian duct syndrome due to deficiency of anti-Mullerian hormone.
Persistent Mullerian duct syndrome due to resistance to anti-Mullerian hormone (AMH), resulting from mutations in the AMH receptor (AMHR) gene.
Infection of the peritoneum related to a peritoneal dialysis catheter.
An oil-in-water nano-emulsion composed of the perfluorocarbon perflenapent, that has oxygen-carrying capacity, can be used as a contrast agent and has potential antihypoxic and radiosensitizing activities. Upon intravenous administration of the perflenapent emulsion, this agent increases the oxygen-carrying capacity of blood, enhances the transport of oxygen to hypoxic and ischemic tissues and increases the oxygen concentration in these tissues. Hypoxic tumors are correlated with increased resistance to radiation treatment; therefore, since perflenapent may increase tumor oxygenation, it may improve the tumor's sensitivity to radiation therapy.
An electrocardiographic recording that demonstrates an R-R interval that exceeds three seconds, irrespective of the underlying rhythm.
A fully human monoclonal antibody directed against the membrane-bound receptor HER3 (ERBB3) with potential antineoplastic activity. Patritumab binds to and inhibits HER3 activation, which may result in inhibition of HER3-dependent PI3K/Akt signaling and so inhibition of cellular proliferation and differentiation. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in solid tumors, including breast, lung, and colorectal tumors of epithelial origin; it has no active kinase domain itself but is activated through heterodimerization with other members of the EGFR receptor family that do.
Gynecomastia that is due to exogenous substances or disease processes.
A parietal decidual spiral vessel with small lumen caliber. The muscular wall of the vessel is not identifiable; its expected location shows foamy macrophages (atherosis).
A rare, aggressive form of morphea characterized by sclerosis of the dermis, fascia, and muscle over large parts of the body, resulting in contractures and immobility.
The outcome of the palpable masses assessment as originally received or collected.
A nutritional supplement composed of a palm oil extract containing high concentrations of mixed tocotrienols, tocopherols, carotenoids, phytosterols, and squalene, with antioxidant and potential hepato-, neuro-, and radio-protective activities. Upon oral administration, the palm extract phytonutrient supplement exerts an antioxidant effect by scavenging free radicals and inhibiting lipid peroxidation. This extract also prevents inflammation by inhibiting the expression of pro-inflammatory cytokines. Altogether, this prevents oxidative stress in cells and may improve symptoms of radiation-induced fibrosis. In addition, this supplement may modulate enzymes that play key roles in neuronal cell degeneration and fatty acid accumulation.
A change in the nucleotide sequence of the PMS2 gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 18 of the PDGFRA gene located within 4q11-q13.
A molecular genetic abnormality indicating the presence of a mutation in exon 14 of the PDGFRA gene located within 4q11-q13.
A molecular genetic abnormality indicating the presence of a mutation in exon 12 of the PDGFRA gene located within 4q11-q13.
A dendritic cell (DC)-based cancer vaccine composed of autologous dendritic cells (DCs) activated with an ovarian tumor cell lysate containing tumor-associated antigens (TAAs) with potential immunostimulatory and antineoplastic activities. Upon administration, the ovarian tumor antigen-activated autologous DC vaccine may stimulate an anti-tumoral cytotoxic T-lymphocyte (CTL) response against ovarian cancer cells expressing ovarian tumor cell-specific antigens, which may result in ovarian tumor cell lysis.
A non-neoplastic or neoplastic disorder that affects the ears, nose, paranasal sinuses, oral cavity, or throat.
A plasma cell neoplasm associated with osteosclerotic and fibrotic changes in the bone trabeculae. Often, the lymph nodes show changes resembling the plasma cell variant of Castleman disease. It is often part of POEMS syndrome which is characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes.
A radiologic finding indicating the presence of multiple radiolucent osteolytic bone lesions observed in a patient with a diagnosis of multiple myeloma.
The outcome of the test or finding as originally received or collected.
Growth hormone deficiency due to an identifiable biological cause.
The outcome of the organ measurements as originally received or collected.
The binding of one or more ocular muscles by orbital bone pieces, resulting in decreased eye mobility.
A melanoma that arises from the structures of the orbit.
Bruising of the skin and soft tissue surrounding the eye.
Any oral disorder occurring as a consequence of injury to the mouth and lips.
Any oral disorder occurring as a consequence of radiation therapy.
Any oral disorder occurring as a consequence of chemotherapy treatment.
Any eye disorder occurring as a consequence of injury to the eye.
An electrolyte-based parenteral emulsion for infusion consisting of a three chamber bag system containing a glucose solution, an amino acid solution and a lipid emulsion that can be used to provide parenteral nutritional supplementation. The lipid emulsion portion contains 20% refined soybean oil and 80% refined olive oil; the amino acid solution contains alanine, arginine, aspartic acid, glutamic acid, leucine, isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. The parenteral nutrition emulsion also contains the electrolytes phosphate and acetate. The three separate bags are mixed together before infusion. Upon infusion, the emulsion provides calories for energy. The lipid portion supplies essential fatty acids that can be incorporated into cell membranes. The amino acids facilitate protein synthesis.
A category of juvenile idiopathic arthritis defined by the presence of arthritis affecting between one and four separate joints during the first six months of disease.
A situation in which the umbilical cord is prolapsed through the cervical canal but not through external os.
Birth trauma caused by excessive pressure to the suboccipital region of the skull resulting in separation of the occipital squama from the lateral or condylar parts of the occipital bone. It is a serious injury that may lead to subdural hemorrhage in the posterior fossa.
The normal development of male secondary sexual characteristics (such as hirsutism, deepening of the voice) in pubertal boys due to testosterone effects.
An inflammation of one or more joints, without loss of articular cartilage or destruction of subchondral bone.
Idiopathic short stature in a child when neither parent is short in stature.
A rare type of multiple myeloma in which the plasma cells synthesize but do not secrete immunoglobulins. As a result, none of the immunoglobulins appear out of the normal range. The symptoms are generally the same with those of immunoglobulin-secreting myeloma; however, the incidence of renal insufficiency is lower in non-secretory myeloma. The diagnosis can be missed because of the absence of monoclonal immunoglobulin in the serum or urine.
A non-neoplastic disorder that affects the smooth, skeletal, or cardiac muscles.
A soft tissue sarcoma that occurs during childhood and has not spread beyond its original site of growth.
An electrocardiographic finding of Q waves that are insufficient for the diagnosis of myocardial infarction. In such cases, a myocardial infarction may be suspected even though ECG diagnostic criteria are absent. (CDISC)
A term that refers to a broad group of diagnoses that may include any disease except for cancer or cancer related disorders.
A recently diagnosed metastatic carcinoma of unknown primary origin.
Clinical, laboratory or molecular evidence, or absence of evidence of disease in a neonate or infant.
The subjective evidence of disease perceived by the patient that can be classified as new or worsening
A finding of decreased regional heart wall motion contractility, which is new compared to prior non-invasive imaging techniques.
A finding of loss of viable myocardium, which is new compared to prior non-invasive imaging techniques.
A disorder of the nervous system related to a vascular etiology.
Secretions which may be thin or tenacious, mucoid or glairy, grayish or milky, occasionally blood tinged, that originate in the vagina and are a consequence of the residual influence of maternal estrogen.
Cardiorespiratory events that are characterized by variable combinations of cessation of breathing, decrease in blood oxygen saturation, and decreased heart rate.
Injury to the central nervous system in the newborn period that occurs when there is insufficient delivery of oxygen to all or part of the brain.
A peptide-based, personalized glioblastoma cancer vaccine consisting of patient-specific glioblastoma derived immunogenic mutated epitopes (neoantigens), with potential immunomodulating and antineoplastic activities. Vaccination with the neoantigen-based glioblastoma vaccine stimulates the host immune system to mount a cytotoxic T lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis. Neoantigens are tumor-specific antigens derived from mutated proteins that are present only in a specific tumor.
A cancer vaccine comprised of a human leukocyte antigen (HLA) A2/A3 restricted HER2/neu (human epidermal growth factor receptor 2; ErbB2) nonapeptide derived from the extracellular domain of the HER2 protein, with potential immunomodulating and antineoplastic activities. Upon intradermal injection, nelipepimut-S may induce a specific cytotoxic T-lymphocyte (CTL) response against HER2/neu-expressing tumor cells. HER2/neu, a tumor-associated antigen and a member of the epidermal growth factor receptor family of tyrosine kinases, is overexpressed in various tumor cell types and plays a key role in tumorigenesis.
A ring of karyorrhectic debris that may exhibit dystrophic mineralization and/or identifiable fetal neutrophil infiltrate in Wharton's jelly that is oriented towards the amniotic surface. The cord has a denser ring externally and a fainter ring centrally.
A severe and often fatal form of necrotizing enterocolitis, in which diffuse ischemia, necrosis, and pneumatosis intestinalis are evident in the small and large intestine. Short bowel syndrome is common among survivors.
The status of an individual who is serving in the National Guard.
A very rare small cell carcinoma that arises from the nose and paranasal sinuses.
A nanoparticle-based suspension containing the water-insoluble taxane paclitaxel, with potential antineoplastic activity. Upon intraperitoneal administration, paclitaxel binds to tubulin and inhibits the disassembly of microtubules, which leads to the inhibition of cell division. The nanoparticle-based formulation is devoid of toxic solvents, such as cremophor; therefore, this agent has fewer side effects than the standard, solvent-based paclitaxel formulation.
A cell-based cancer vaccine composed of dendritic cells (DC) pulsed with peptides derived from the tumor-associated antigens human cancer/testis antigen NY-ESO-1 and melanoma antigen recognized by T-cells (MART-1/Melan-A), with potential immunostimulatory and antineoplastic activities. Upon administration, the NY-ESO-1/MART-1-peptide pulsed DC vaccine may stimulate the immune system to mount an anti-tumor cytotoxic T-lymphocyte (CTL) response against NY-ESO-1/MART-1-expressing tumor cells, which may result in tumor cell lysis. NY-ESO-1 is expressed both in normal testes and on the surfaces of various tumor cells. MART-1 is expressed by melanoma cells.
A change in the nucleotide sequence of the NF1 gene.
A melanoma that arises from a mucosal site.
An adenocarcinoma arising from the colon of a mouse. It can be used as a mouse model of the human disease.
The variable or non-uniform coloring of the placental parenchyma indicating variable contribution of the blood contained within the fetal vessels to the color of the parenchyma.
Persistent volitional repetition of non-purposeful movement.
The outcome of the morphology assessment as originally received or collected.
An indication or description that morphology assessment data is a derived value.
An indication or description that morphology data is a baseline value.
A chronic lung disorder associated with pulmonary maldevelopment, scarring, and/or inflammation that develops in preterm neonates exposed to supplemental oxygen for at least 28 days. For infants born before 32 weeks gestation with moderate BPD, there is a supplemental oxygen requirement of less than 30% at 36 weeks postmenstrual age or earlier discharge. For infants born after 32 weeks with moderate BPD, there is a supplemental oxygen requirement of less than 30% at 56 days post-natal age or at earlier discharge.
The presence of more than one variant of morphea in a single patient.
A commercial combination preparation, by Allergan, containing mineral oil and white petrolatum. Refresh PM Lubricant, an ointment, is used to moisturize and relieve discomfort due to ocular dryness and irritation.
A chronic lung disorder associated with pulmonary maldevelopment, scarring, and/or inflammation that develops in preterm neonates exposed to supplemental oxygen for at least 28 days. For infants born before 32 weeks gestation with mild BPD, there is no supplemental oxygen requirement at 36 weeks postmenstrual age or earlier discharge. For infants born after 32 weeks with mild BPD, there is no supplemental oxygen requirement at 56 days post-natal age or at earlier discharge.
The outcome of the microscopic assessment as originally received or collected.
An indication or description of a correlation between death and a microscopic finding.
The standard character or string for representation and reporting of microscopic findings data.
An indication or description that microscopic findings data is a baseline value.
A malignant neoplasm that has spread to the soft tissues from another anatomic site.
The end of a device is fractured or damaged.
A part of a device has been fractured or damaged.
A gel formulation composed of the hydrochloride salt form of mechlorethamine, which is a nitrogen mustard alkylating agent and an analog of sulfur mustard, with antineoplastic and immunosuppressive activities. Upon topical application, mechlorethamine is metabolized to an unstable, highly reactive ethyleniminium intermediate that binds to and alkylates DNA, with a high affinity to the N7 nitrogen of guanine residues. This results in DNA base pair mismatching, DNA interstrand crosslinking, the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis.
A gel-based formulation containing an extract of the herb Matricaria chamomilla (M. recutita or German chamomile), which is native to eastern and southern Europe, belongs to the Asteraceae family and is high in flavonoids, with potential anti-inflammatory, skin protective, moisturizing, anti-bacterial, anti-oxidant and calming activities. M. recutita extract contains flavonoids, including apigenin, luteolin and quercetin, as well as coumarins, herniarin, umbelliferone, anthemic acid, anthemidine, tannin and matricarin. Upon topical application of the Matricaria recutita infusion, the active ingredients in the chamomile may exert anti-inflammatory, calming and anti-oxidant effects on the skin and may protect the skin against radiotherapy-induced dermatitis.
A gel-based formulation containing an extract of the herb Matricaria chamomilla (M. recutita or German chamomile), which is native to eastern and southern Europe, belongs to the Asteraceae family and is high in flavonoids, with potential anti-inflammatory, skin protective, moisturizing, anti-bacterial, anti-oxidant and calming activities. M. recutita extract contains flavonoids, including apigenin, luteolin and quercetin, as well as coumarins, herniarin, umbelliferone, anthemic acid, anthemidine, tannin and matricarin. Upon topical application of the Matricaria recutita gel, the active ingredients in the chamomile may exert anti-inflammatory, calming and anti-oxidant effects on the skin and may protect the skin against radiotherapy-induced dermatitis.
The tumor shows metastasis throughout the pleural and/or pericardial spaces or metastasis to distant sites.
The tumor shows invasion into the capsule.
An observation that the fetal membranes are inserted at the edge of the placental disc.
Faulty healing of bone, resulting in improper anatomical alignment.
A primary or metastatic malignant neoplasm involving the cardiovascular system.
Blockage in the biliary tract caused by a malignant neoplasm.
Symptoms, physical examination results, and/or laboratory test results related to the male reproductive system.
The presence of macroscopically visible residual tumor at the edge of a surgically excised specimen.
The outcome of the macroscopic findings assessment as originally received or collected.
An indication or description of a correlation between death and a macroscopic finding.
The standard character or string for representation and reporting of macroscopic findings data.
A change in the nucleotide sequence of the MSH6 gene.
A change in the nucleotide sequence of the MLH1 gene.
A change in the nucleotide sequence of the MEN1 gene.
A pathologic and/or clinical finding indicating the spread of a lymphomatous process to an anatomic site other than lymph nodes and skin.
A synthetic tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one alkaloid analogue with potential antineoplastic activity. Lurbinectedin covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death.
A severe, persistent headache that occurs in patients with systemic lupus erythematosus, and is nonresponsive to narcotic analgesia.
An electrocardiographic finding of small QRS amplitudes (less than 500 microvolts) in all limb leads. (CDISC)
A grade I or grade II astrocytic tumor. This category includes pilocytic astrocytoma (grade I), subependymal giant cell astrocytoma (grade I), and diffuse astrocytoma (grade II).
A decrease in the openness of a side branch of a blood vessel.
A decrease in the openness of a major, or great, blood vessel.
Loss of protein expression of the BRG-associated factor 250a (BAF250a). It is caused by mutation of the tumor-suppressor gene ARID1A. It is linked to tumor progression and poor prognosis in various cancers.
A rare autosomal dominant inherited disorder of connective tissue caused by mutations in either the TGFBR1 or TGFBR2 gene. Like Loeys-Dietz syndrome type I the disease is characterized by enlargement of the aorta and other arteries, and arterial tortuosity, but skeletal signs are typically less severe or absent in type 2. Skin abnormalities, such as velvety skin are often present in type 2.
Angiofollicular lymphoid hyperplasia that presents with localized lymphadenopathy.
A rare carcinoma that arises from the intrahepatic bile ducts and is composed of malignant glandular cells and malignant squamous cells.
A formulation composed of the hydrochloride salt form of the anthracenedione antibiotic mitoxantrone encapsulated within liposomes, with potential antineoplastic activity. Upon intravenous administration, mitoxantrone intercalates into and forms crosslinks with DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, which both results in DNA strand breaks and prevents DNA synthesis. This leads to the induction of apoptosis in the rapidly dividing cancer cells. The liposomal delivery of mitoxantrone improves drug penetration into tumors and decreases drug clearance, thereby increasing drug circulation and therapeutic efficacy while lowering the toxic effects.
A liposomal formulation containing curcumin, a poorly water-soluble polylphenol pigment isolated from the plant Curcuma longa, with potential antineoplastic, chemopreventive, antioxidant, anti-angiogenic and anti-inflammatory activities. Upon intravenous administration of liposomal curcumin, this agent blocks the formation of reactive-oxygen species, neutralizes free radicals, and exhibits anti-inflammatory properties as a result of inhibition of cyclooxygenases (COX) and other enzymes involved in inflammation. In addition, curcumin disrupts various cell signal transduction pathways involved in carcinogenesis, inhibits the activity of nuclear factor-kappa B (NF-kB), SRC, and annexin A2 (ANXA2), and reduces the expression of both matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor receptor 2 (VEGFR2). This prevents and/or inhibits tumor cell formation and proliferation. Liposome encapsulation of curcumin improves its efficacy, when compared to the administration of unencapsulated curcumin.
An indication as to whether limb failure occurred.
A finding of diffuse metabolic activity at the primary tumor or nodal sites that is greater than background uptake but less than liver uptake, detected by PDG-PET.
A finding of focal metabolic activity at the primary or nodal sites that is greater than liver uptake, as detected by FDG-PET.
A finding of metabolic activity at the primary or nodal sites that is greater than liver uptake, but can be attributed to inflammation activity, as detected by FDG-PET.
An indication as to whether a performed procedure of a target lesion is considered successful.
An indication as to whether clinical or functional ischemia is present before lesion revascularization occurred.
An indication as to whether an appropriate clinical context was present before lesion revascularization occurred.
An indication as to whether there is re-narrowing of a lesion site following treatment of a prior stenosis, to a diameter stenosis of greater than 50% at the previously treated lesion site.
An indication as to whether lesion failure occurred.
The loss of a pregnancy between 13 and 22 weeks.
A late stage of Lyme disease that may present in untreated patients months to years after a tick bite manifested with intermittent bouts of arthralgia, arthritis and neurologic complaints.
The length, in cm, of the longest axis of the chorionic disc.
Full-thickness wound of the eyewall (cornea and/or sclera) caused by a sharp object.
A change in the amino acid residue at position 13 in the GTPase KRas protein where glycine has been replaced by another amino acid.
A change in the amino acid residue at position 12 in the GTPase KRas protein where glycine has been replaced by another amino acid.
A change in the nucleotide sequence of the KRAS gene that that results in constitutive signal transduction, which stimulates downstream signaling pathways involved in cell growth, proliferation, invasion, and metastasis. The presence of KRAS activating mutations in colorectal cancer and non-small-cell lung cancer is used identify the subgroup of patients who are most likely to respond to EGFR antagonist chemotherapy.
A molecular genetic abnormality indicating the presence of a mutation in exon 17 of the KIT gene located within 4q11-q12.
Localized scleroderma presenting before the age of eighteen.
A rare form of juvenile dermatomyositis that manifests with characteristic cutaneous findings for at least six months in the absence of any detectable muscle involvement.
Myocardial infarction associated with CABG. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525-2538.)
Myocardial infarction associated with stent restenosis as detected by coronary angiography or at autopsy. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525-2538.)
Myocardial infarction associated with stent thrombosis as documented by angiography or at autopsy. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525-2538.)
Myocardial infarction associated with PCI. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525-2538.)
Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischaemia, accompanied by presumably new ST elevation, or new LBBB, or evidence of fresh thrombus in a coronary artery by angiography and/or at autopsy, but death occurring before blood samples could be obtained, or at a time before the appearance of cardiac biomarkers in the blood. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525-2538.)
Spontaneous myocardial infarction related to ischaemia due to a primary coronary event such as plaque erosion and/or rupture, fissuring, or dissection. (Universal definition of myocardial infarction, Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction, Eur Heart J (2007) 28 (20): 2525-2538.)
A change in the amino acid residue at position 617 in the tyrosine-protein kinase JAK2 protein where valine has been replaced by another amino acid. A change to phenylalanine at this position is associated with polycythemia vera.
A change in the amino acid residue at position 875 in the tyrosine-protein kinase JAK2 protein where threonine has been replaced by asparagine.
A nucleotide substitution at position 2624 of the coding sequence of the JAK2 gene where cytosine has been mutated to adenine.
Occurrence of the first menstrual period in a girl before the lower limit of the normal age range for the reference population, without other signs of puberty.
An indication as to whether the subject has symptoms of ischemic discomfort.
Bleeding into the lateral cerebral ventricles and the adjacent brain tissue of a newborn infant.
Bleeding into the cerebral ventricles that occurs during labor and/or delivery.
An acute symptomatic tearing of the uterine wall after the onset of labor.
Bleeding into the brain tissue of a newborn infant.
Bleeding within the skull of a newborn infant occurring during labor and/or delivery.
An adenocarcinoma that arises from the nasal cavity and paranasal sinuses. Histologically it resembles intestinal carcinoma or adenoma. It is associated with lengthy occupational exposure to dust.
A focus of maternal thrombus within the intervillous space, often with peripheral villous compression. The clot may be wholly or minimally laminated reflecting age.
Failure to thrive due to poor intake by the infant, inadequate feeding schedule or insufficient maternal production of breast milk.
An electrocardiographic recording that does not demonstrate any significant signs of ischemia or conduction abnormalities.
A feeling of unrest and/or an inability to feel calm or relaxed.
A topical, aqueous gel formulation containing the mebutate salt form of ingenol, a selective small-molecule activator of protein kinase C (PKC) that is isolated from the sap of Euphorbia species, with potential antineoplastic activity. Upon topical application of the ingenol mebutate gel, ingenol activates various PKC isoforms, which induces apoptosis in certain tumor cells, including myeloid leukemia cells, melanoma cells, and basal cell carcinoma cells. The PKC family consists of signaling isoenzymes that regulate many cell processes, including proliferation, differentiation, and apoptosis.
Infiltrating transitional cell carcinoma of the bladder which is associated with the presence of in situ or infiltrating urethral carcinoma.
Inflammation of the cornea secondary to an infectious process.
A finding of abnormal heart wall motion contractility in response to stress, and which is not seen at rest.
A radiopharmaceutical formulation containing human, serum albumin (HSA) labeled with indium In 111 (In-111) in macroaggregates (MAA) with potential usage as a diagnostic imaging agent. Upon injection of indium In 111-labeled macroaggregated albumin and subsequent imaging, biodistribution patterns can be assessed and the expected distribution of agents with similar particle sizes may be predicted.
Increased number of syncytiotrophoblasts with clusters of apoptotic bodies compared to what would be expected for gestational age.
A finding of an increased amount of either B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide
Non-identically shaped visual field defect in the same location in both eyes.
A maternal placental surface that lacks a smooth basal plate. Missing pieces of the placental parenchyma are appreciable.
An indication as to whether there is re-narrowing of a stent implanted at a lesion site to treat a prior stenosis, to a diameter stenosis of greater than 50% within the stent.
A recombinant immunotoxin fusion protein consisting of single-chain variable-region antibody fragments (scFvs), which contain disulfide stabilized heavy- (Vh) and light- (Vl) chain variable regions of the monoclonal antibody D2C7 (D2C7-scdsFv), targeting both the wild-type form (EGFRwt) and the in-frame deletion mutant form (EGFRvIII) of epidermal growth factor receptor (EGFR), and fused, via a 15-amino acid peptide linker to domains II and III of the Pseudomonas exotoxin A (PE38KDEL) (D2C7-(scdsFv)-PE38KDEL), with potential antineoplastic activity. Upon intratumoral administration by convection-enhanced delivery, the scFv moiety of immunotoxin anti-EGFR scFv monoclonal antibody fragment immunotoxin D2C7-(scdsFv)-PE38KDEL targets and binds to a specific amino acid epitope present in the extracellular domain of both the EGFRwt and EGFRvIII proteins. This binding facilitates the internalization of the immunotoxin by tumor cells. Inside the cells, the exotoxin portion of the fusion protein binds to translation elongation factor 2 (EF-2), and deactivates EF-2 through ADP ribosylation. This results in the inhibition of protein synthesis, the induction of apoptosis and a reduction in cell proliferation of EGFRwt/EGFRvIII-expressing tumor cells. Compared to intact IgG antibodies and single-chain antibodies, scFvs are smaller with increased tumor-penetrating capacity which may enhance therapeutic efficacy. The EGFR gene, a transmembrane receptor tyrosine kinase, and its mutant form, EGFRvIII, which contains a deletion of exons 2-7 of the EGFR gene, are frequently amplified and overexpressed in a variety of cancers. KDEL increases the toxin's intracellular retention, thereby enhancing its cytotoxicity.
The outcome of the immunogenicity specimen assessment as originally received or collected.
An indication or description that immunogenicity specimen assessment data is a baseline value.
An orally bioavailable, immediate-release (IR), liquid formulation containing the hydrochloride salt form of oxymorphone, a semisynthetic opioid with potent analgesic activity. Upon oral administration, oxymorphone binds to and activates opioid receptors, specifically mu-receptors, in the central nervous system (CNS), thereby mimicking the effects of endogenous opioids and providing analgesia.
Tall stature for which no underlying cause can be found.
Insufficient secretion of growth hormone for which no underlying cause can be found.
An isosmotic solution containing icodextrin, a starch-derived, water-soluble glucose polymer, used in peritoneal dialysis and for the prevention of adhesion after surgery. Due to its iso-osmotic nature and inability to cross the peritoneal membrane, the icodextrin solution, upon administration into the peritoneal cavity, is able to exert osmotic pressure. This allows for the removal of excess fluids and waste products in dialysis patients. In addition, icodextrin can provide a barrier between tissue surfaces when administered during surgery. This physically separates tissues, prevents adhesion after surgery and promotes wound healing.
Growth failure due to medical intervention.
A change in the amino acid residue at position 172 in the isocitrate dehydrogenase [NADP], mitochondrial protein where arginine has been replaced by another amino acid. Mutations at this position are found in patients with acute myeloid leukemia following myelodysplastic syndromes and is associated with shorter overall survival.
A change in the amino acid residue at position 140 in the isocitrate dehydrogenase [NADP], mitochondrial protein where arginine has been replaced by another amino acid. Mutations at this position are found in patients with acute myeloid leukemia following myelodysplastic syndromes and is associated with shorter overall survival.
A change in the nucleotide sequence of the IDH2 gene.
A variation in the amino acid sequence for the isocitrate dehydrogenase [NADP] cytoplasmic protein.
A change in the amino acid residue at position 132 in the isocitrate dehydrogenase [NADP] cytoplasmic protein where arginine has been replaced by another amino acid. Mutations at this position occur frequently in high-grade gliomas but not in other solid tumors.
A change in the nucleotide sequence of the IDH1 gene.
Umbilical cord with apparent reduced helical coiling of the arteries around the vein.
A hyperpolarized pyruvate labeled with carbon C 13, with potential usage in the diagnostic imaging of cancer cells. Upon administration, carbon C 13 hyperpolarized pyruvate (13C-pyruvate) is taken up by cancer cells and is further metabolized to lactate and alanine for use in glycolysis, lipogenesis and protein synthesis, to support the enhanced metabolic needs of tumor cells. As tumor cells are rapidly proliferating, their uptake of pyruvate and its subsequent conversion to alanine and lactate are higher than non-proliferating cells. Upon nuclear magnetic resonance (NMR)-based imaging (MRI), both hyperpolarized 13C-pyruvate as well as its metabolites can be detected and visualized in cancer cells; this may aid in the diagnosis of cancer. Hyperpolarization of 13C-pyruvate, using dynamic nuclear polarization (DNP), enhances NMR signals.
Umbilical cord with apparent increased helical coiling of the arteries around the vein.
An immediate rejection of transplanted tissue caused by the presence of preformed antibodies to donor human leukocyte antigens.
A topical cream formulation containing hyaluronic acid (HA) with wound repair promoting, skin moisturizing and potential radioprotective activities. Upon application of the topical cream, HA adheres to injured tissues, provides hydration to the skin, and protects against dehydration and chemical or mechanical irritation. Hyaluronate, a non-sulfated glucosaminoglycan, is a major component of the extracellular matrix in connective, epithelial, and neural tissues and contributes significantly to cell proliferation and migration.
Presence of preformed antibodies to donor human leukocyte antigen (HLA).
A finding of a hospitalization event due to a heart failure diagnosis.
Prostate carcinoma that does not respond to hormone therapy.
A bilateral visual field defect on the same side of visual space of each eye (right or left).
A staging classification system for hepatocellular carcinoma that uses variables related to tumor stage, liver functional status, physical status, and cancer-related symptoms, and links the stages with a treatment algorithm. (HPB (Oxford) 2005; 7(1):35-41)
The deposition of hemosiderin in a focus of thrombus within the placental intervillous space.
The deposition of hemosiderin along the gravid uterine wall.
The deposition of hemosiderin along the gravid uterine fundus beneath the placenta.
The presence of bacteria in the blood caused by an infected hemodialysis catheter.
A finding of heart failure through a non-invasive diagnostic technique.
A finding of heart failure through an invasive diagnostic technique.
A response indicating that something occurs rarely or with very little intensity.
An orally bioavailable, therapeutic bivalent vaccine composed of heat- and chemical-inactivated hepatitis C virus (HCV) antigens derived from the blood of HCV-infected carriers, with potential immunomodulating activity. Upon oral administration of the HCV antigen therapeutic bivalent vaccine V5, the HCV antigens may stimulate the host immune system to mount an immune response against HCV-infected cells, thereby preventing further HCV-infection and HCV-induced liver injury.
A dinucleotide antimetabolite of a decitabine linked via phosphodiester bond to a guanosine, with potential antineoplastic activity. Following metabolic activation by phosphorylation and incorporation into DNA, guadecitabine inhibits DNA methyltransferase, thereby causing genome-wide and non-specific hypomethylation, and inducing cell cycle arrest at S-phase. This agent is resistant to cytidine deaminase, hence may result in gradual release of decitabine both extra and intracellularly, leading to more prolonged exposures to decitabine.
Subnormal linear growth rate in an infant, child or adolescent based on the normative values for the age and sex of the reference population; the cause of the growth failure is unknown.
Infection of an infant from birth to less than seven days of life caused by Group B Streptococcus (Streptococcus agalactiae) from a colonized mother.
The presence of microscopically visible residual tumor at the edge of a surgically excised specimen that otherwise looks macroscopically normal.
The absence of tumor cells at the edge of a surgically excised specimen, both macroscopically and microscopically.
A separation of the placenta from the uterine wall that is manifested by a retroplacental hematoma with villous compression and change in villous coloration that is reflective of lesion age.
An orally available powder-based nutritional supplement containing the spores of the mushroom Ganoderma lucidum (Ganoderma l.), a traditional Chinese medicine, with potential protective, sedative, anti-oxidant, immunomodulating, and antineoplastic activities. The spores contain various bioactive components including polysaccharides, triterpenoids, peptidoglycans, amino acids, fatty acids, vitamins, and minerals. Upon oral administration of the Ganoderma lucidum spores powder capsule, the active ingredients may modulate the immune system, may activate dendritic cells, natural killer cells, and macrophages and may modulate the production of certain cytokines, such as tumor necrosis factor-alpha (TNFa), interleukin (IL) 1-beta (IL-1b), IL-2, IL-6 and IL-8. This supplement may improve cancer-related fatigue and may be used as a sleep aid; it may also have a beneficial effect on the heart, lung, liver, pancreas, kidney, and the central nervous system.
A radiopharmaceutical composed of the glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 linked by the macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) to the positron-emitting radionuclide gallium Ga 68, with potential use in diagnostic imaging upon positron emission tomography (PET). Upon administration of gallium Ga 68-DOTA-exendin-4, the exendin-4 moiety binds to GLP-1R and is subsequently internalized. The radionuclide moiety can be detected using PET and GLP-1R-expressing tumors can be localized. GLP-1R, located on beta cells, is overexpressed on insulinomas, which are insulin-secreting neuroendocrine tumors.
In pregnancies with more than one fetus, the composite structure that results from the growth of two (or more) placental chorionic discs such that the placental masses abut one another and are delivered as a single unit but can manually separated into individual units.
A situation in which the umbilical cord is prolapsed through the cervix and into the vagina.
A broken ulna sustained during the birthing process.
A broken vertebra sustained during the birthing process.
A broken radius sustained during the birthing process.
A broken nasal bone sustained during the birthing process.
An injury sustained during the birthing process in which the continuity is broken in any bone that is longer in length than width.
A broken humerus sustained during the birthing process.
A broken femur sustained during the birthing process.
An injury sustained during the birthing process in which the continuity is broken in the clavicle.
A broken bone sustained during the birthing process.
Birth injury sustained during a forceps-assisted delivery.
The outcome of the food and water consumption assessment as originally received or collected.
An ophthalmic suspension containing the acetate form of fluorometholone, with potential anti-infective and immunosuppressive activities. Upon ocular administration, fluorometholone binds to glucocorticoid receptors in the cytoplasm and forms a receptor-ligand complex, which translocates to the nucleus where it binds to glucocorticoid response elements (GRE) in the promoter region of target genes. This leads to the expression of specific target genes that control inflammation. Specifically, by inducing the expression of lipocortins that inhibit the enzymatic activity of phospholipase A2, the release of arachidonic acid is blocked, which prevents the production of inflammatory mediators, and inflammatory-induced ocular swelling, redness and itching.
A finding of decreased blood flow in the microcirculation of the heart.
A fetus that does not grow beyond the 10th percentile of conventionally accepted weight for gestational age and shows evidence of oligohydramnios.
A fetus that does not grow beyond the 10th percentile of conventionally accepted weight for gestational age and has abnormal Doppler studies.
A fetus that does not grow beyond the 10th percentile of conventionally accepted weight for gestational age and whose abdominal circumference falls below the tenth percentile.
A focus of thrombus adhered to the wall of a fetal stem vessel. It can be completely or partially obstructive and may lead to avascular villi.
A focus of thrombus adhered to the wall of a fetal stem vessel. It can be completely or partially obstructive and may lead to downstream villous injury and calcification.
Increased nucleated red blood cells within the fetal circulation.
A neutrophilic infiltrate arising from fetal vessels in the chorionic plate and oriented towards the amniotic cavity.
Symptoms, physical examination results, and/or laboratory test results related to the female reproductive system.
Violation of Tenon's capsule with prolapse of orbital fat into the sub-Tenon's space.
Germ cell tumor that arises from the testis and is diagnosed in at least two relatives.
Neuroblastoma inherited from a parent and caused by mutations in the ALK or PHOX2B genes. Familial neuroblastomas have a higher incidence of multiple primary tumors and are diagnosed at an earlier age.
Idiopathic tall stature in a child when either one or both parents is tall in stature.
Idiopathic short stature in a child when either one or both parents is short in stature.
Failure to achieve a linear growth rate sufficient to restore height to within the normative range for the reference population.
A condition characterized by reduced or absent movement of the ipsilateral face as a consequence of an injury to the seventh cranial nerve sustained during the birthing process.
A mutation in the region of the FLT3 gene that encodes the second tyrosine kinase domain of the receptor-type tyrosine-protein kinase FLT3 that causes the stabilization of the activation loop of the kinase domain. FLT3 activation loop mutations lead to constitutive tyrosine kinase activity and are associated with acute myeloid leukemia.
A constellation of disorders involving mutations of the FGFR3 gene, which result in abnormal growth of bone and cartilage; this includes achondroplasia and hypochondroplasia.
A molecular genetic abnormality indicating the presence of multiple copies of the FGFR gene.
A molecular genetic abnormality indicating the presence of multiple copies of an FGF family gene.
A nuclear medicine finding obtained using FDG-PET imaging technique.
A change in the nucleotide sequence of the FAP gene.
Extension of a malignant neoplasm beyond the lymph node capsule.
Oligoarticular juvenile idiopathic arthritis that eventually involves more than four separate joints.
An indication or description of a collected exposure occurrence.
An indication or description of whether a collected exposure specimen was obtained from a subject that has abstained from food and possibly water for the prescribed amount of time.
A malignant tumor that arises in the brain stem or adjacent cranial nerves, consisting of variable populations of cells which demonstrate both neuronal and myoblast differentiation. (INHAND)
A malignant neoplasm of the brain or spinal cord originating from astrocytes.
A benign neoplasm in the superficial dermis with direct association to the epidermis, composed of well differentiated squamous epithelium and a central cavity filled with concentric layers of keratin; a pore (opening in the epidermis) may be present. (CDISC)
A benign tumor of the pancreas with morphologic characteristics of endocrine, acinar and ductal cells. (INHAND)
An indication as to whether type 1 and type 2 myocardial infarction is excluded as a diagnosis.
Specifies whether result values should be excluded from the statistical analysis.
Specifies whether the vital signs result values should be excluded from the statistical analysis.
Specifies whether the organ measurement result values should be excluded from the statistical analysis.
Specifies whether the laboratory test result values should be excluded from the statistical analysis.
Specifies whether the food and water consumption result values should be excluded from the statistical analysis.
Specifies whether the ECG result values should be excluded from the statistical analysis.
Specifies whether the clinical observation result values should be excluded from the statistical analysis.
Specifies whether the body weight gain result values should be excluded from the statistical analysis.
Specifies whether the body weight result values should be excluded from the statistical analysis.
An achievement of either a complete disease response, or a partial disease response of at least 6 months duration in a trial or treatment where the overall response rate is less than 10 percent.
A cream containing Evaux thermal spring water, with potential moisturizing and skin protecting activities. Upon application to the skin, Evaux spring water-based cream forms a protective barrier, which prevents water loss, provides moisture to the skin, protects the skin from damage, and soothes irritated skin. The Evaux thermal spring water contains the trace elements lithium and manganese which may help heal the skin.
An indication as to whether the event meets the criteria for a clinical endpoint.
A condition affecting premature infants characterized by white matter injury, which is frequently accompanied by neuronal/axonal disease, that may affect all brain parenchymal structures and is due to a combination of destructive processes as well as maturational and trophic disturbances.
An abnormally high blood pressure reading.
Recent diagnosis of rheumatoid arthritis (usually within one to two years of onset) during which treatment may be more effective and possibly improve the disease course.
An early stage of Lyme disease that may present within 3-30 days after a tick bite with a red, concentrically-expanding rash (erythema migrans), fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes.
Early stages of inflammatory arthritis, when the underlying diagnosis is uncertain, usually little or no joint damage has occurred. Treatment may alter the disease course (e.g., potentially avert progression to full RA or other diagnosis).
An early stage of Lyme disease that may present days to weeks after a tick bite with relapsing signs of a red, concentrically-expanding rash (erythema migrans), facial palsy, meningismus, neuralgia, heart palpitations, and dizziness.
A finding of heart failure during a visit to the emergency room or a doctor's office.
An indication as to whether ECG interval measurements were based on the same lead.
The level of awareness of an organism during an electrocardiogram assessment.
An indication as to whether replicate ECGs for time points during the baseline portion of the study were included.
An indication as to whether replicate ECGs for time points during the on-treatment portion of the study were included.
An indication as to whether the 10-second ECGs for this study were extracted from a continuous recording.
A morphologic finding indicating the presence of dysplastic epithelial changes in an intestinal tissue sample that is affected by Crohn disease.
An orally available multikinase inhibitor that targets Raf kinase and various receptor tyrosine kinases (RTKs), with potential antineoplastic activity. Upon oral administration, donafenib binds to and blocks the activity of Raf kinase, and inhibits Raf-mediated signal transduction pathways. This inhibits cell proliferation in Raf-expressing tumor cells. In addition, this agent may inhibit unidentified RTKs, and thus may further block tumor cell proliferation in susceptible tumor cells. Raf, a serine/threonine protein kinase, plays a key role in the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway. Deregulation of this pathway often results in tumor cell proliferation and survival.
A carcinoma that arises from the distal part of the urethra.
A bacterial infection by Listeria monocytogenes in two or more non-contiguous sterile body compartments.
Malposition and dysfunction of a peritoneal dialysis catheter.
Abnormally high or low anti-Müllerian hormone levels.
A defect in the Anti-Muellerian hormone receptor.
Malposition of a peritoneal dialysis catheter.
The outcome of the disease response assessment as originally received or collected.
An indication or description of a record that is considered to be the accepted and final evaluation for the disease response.
The spread or migration of cancer cells through the wall of an organ into surrounding organs and/or adjacent tissues.
A cough and cold syrup containing the first-generation antihistamine diphenhydramine hydrochloride and the decongestant phenylephrine hydrochloride. Diphenhydramine blocks the effects of histamine, thereby preventing symptoms such as sneezing and itchy, watery eyes, runny nose and sore throat. In addition, this agent causes drowsiness and can be used as a sleep aid. Phenylephrine, a sympathomimetic agent, acts as a decongestant by inducing vasoconstriction mediated via alpha-adrenergic receptors. This reduces blood flow, decreases swelling and prevents nasal and sinus congestion.
An oral rinse containing the antihistamine diphenhydramine hydrochloride, the topical anesthetic agent lidocaine, and the antacids aluminum hydroxide and magnesium hydroxide (DLA), with potential analgesic and anti-mucositic activities. Upon swishing and gargling with the DLA rinse, the diphenhydramine may provide analgesia; the lidocaine exerts an anesthetic activity which may further relieve mucositis-associated pain; the antacids, aluminum and magnesium hydroxide, are able to provide a coating of the rinse over the lesions in the oral mucosa and neutralize acids. Altogether, this rinse may reduce the symptoms of chemo- and radiotherapy-induced mucositis.
Bleeding originating from any part of the digestive system.
A severe hypersensitivity-like reaction occurring during dialysis due to exposure to the dialysis membrane.
Local infection involving the subcutaneously tunneled portion of a dialysis catheter.
A crack or break in a dialysis catheter caused by material weakness or mechanical compression.
Local infection at the dialysis catheter exit site.
Any issue that arises as a consequence of a problem with a patient's dialysis access.
A syrup-based formulation containing the antitussive dextromethorphan hydrobromide and the decongestant phenylephrine hydrochloride. Dextromethorphan exerts its antitussive activity by raising the threshold for coughing in the cough center. Phenylephrine, a sympathomimetic agent, acts as a decongestant by inducing vasoconstriction mediated via alpha-adrenergic receptors. This reduces blood flow, decreases swelling and prevents nasal and sinus congestion.
An orally administered syrup containing the antitussive dextromethorphan hydrobromide alone or in combination other agents that relieve cough and/or cold symptoms. Dextromethorphan is used to suppress cough by raising the threshold for coughing in the cough center in the central nervous system (CNS).
A device or pieces of the device remain in a patient.
An appliance or mechanism that continues to be implanted.
A status indicating that a device was introduced to the subject for use but did not meet its intended goal and was removed.
A response indicating a certainty that something occurs with little frequency or intensity.
A response indicating a certainty that something occurs with much less frequency or intensity as previously.
A finding of strong focal metabolic activity at the primary or nodal sites that is greater than liver uptake, as detected by FDG-PET.
An orally bioavailable, small-molecule focal adhesion kinase (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. Defactinib inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including those involving RAS/MEK/ERK and PI3K/Akt, thus inhibiting tumor cell migration, proliferation, survival, and tumor angiogenesis. The tyrosine kinase FAK, a signal transducer for integrins, is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types.
Diminished clarity of vision with current correction (glasses and/or contacts).
Diminished clarity of vision without optical correction (glasses and/or contacts).
Diminished clarity of vision despite optimal optical correction (glasses and/or contacts).
Impaired ability to focus on a subject or idea.
An indication as to whether the image reconstruction took into account the time-activity curve during which the radiolabeled tracer decayed as it spread through the body during the image acquisition.
The outcome of the death diagnosis assessment as originally received or collected.
A proprietary lipid emulsion containing five vaccines: diphtheria, pertussis, tetanus (DPT), typhoid, Staphylococcus aureus, paratyphoid A and paratyphoid B, with potential immunostimulating activity. Subcutaneous administration of the DPT/typhoid/Staphylococcus aureus/paratyphoid A/paratyphoid B vaccine activates the immune system and may both abrogate tumor-induced immune tolerance and induce an antitumor immune response, which may eradicate the tumor.
An antibody-drug conjugate (ADC) composed of an antibody against the tumor-associated antigen (TAA) lymphocyte antigen 6 complex locus E (Ly6E) and linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the antibody moiety of DLYE5953A targets and binds to Ly6E expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills, through an as of yet unknown mechanism of action, the Ly6E-expressing cancer cells. Ly6E, an interferon (IFN)-inducible glycosylphosphatidylinositol (GPI)-linked cell membrane protein, is expressed on a variety of tumor cell types.
A variant form of nucleophosmin with cytoplasmic expression. These variants have either a 4-base or 9-base insertion in exon 12 of the NPM1 gene. Acute myelogenous leukemia with normal cytogenetics and cytoplasmic nucleophosmin (NPMc+ AML) constitutes about one third of the cases of primary AML in adults.
Self-injury caused by making cuts into the skin.
Intralymphatic metastasis of cutaneous melanoma between the primary melanoma site and the regional lymph node basin. (from AJCC 7th Ed.)
Displacement of the crystalline lens from the visual axis.
An ultrastructural finding in breast adipose tissue that indicates macrophage infiltration to sites of adipocyte necrosis. This finding is associated with obesity and breast tissue inflammation and may be an indicator for increased risk of neoplastic breast disease.
An indication as to whether there is a new acute reduction in flow at the original percutaneous coronary intervention site in the coronary vessel.
An angiographic finding of pathologic material in a coronary vessel, which obstructs myocardial perfusion.
Identically shaped visual field defect in the same location in both eyes.
An infection, characterized by the rash of chickenpox or shingles, that is caused by the varicella-zoster virus transmitted directly from the mother to the fetus or neonate during late pregnancy or childbirth.
Insufficient production of estrogen or testosterone in the ovaries or testes due to decreased secretion of gonadotropins as a result of pituitary or hypothalamus gland dysfunction that is present at birth.
Ovarian or testicular dysfunction associated with high levels of gonadotropins, that is present at birth.
A morphologic defect of an organ, part of an organ, or a larger region of the body that results from the extrinsic breakdown of, or an interference with, an originally normal developmental process.
A congenital lymphatic malformation usually arising from the neck and characterized by cystic dilation of the lymphatic vessels.
A tic that involves multiple muscles or muscle groups, or words or sentences.
A maternal placental surface that is smooth and without appreciable parenchymal loss.
Cognitive impairment caused by cancer treatment.
Thin rings of enhancement visible in MRI that are clustered together around breast ducts in an area that is neither a mass nor a foci.
The outcome of the clinical observation as originally received or collected.
A humanized monoclonal antibody against the extracellular domain of the human receptor tyrosine kinase-like orphan receptor 1 (ROR1), with potential antineoplastic activity. Upon administration, cirmtuzumab binds to ROR1 and blocks ROR1-mediated signaling. This prevents tumor cell proliferation in cancer cells overexpressing ROR1. ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is normally expressed during embryogenesis. It is overexpressed in certain leukemias and solid tumors, but minimally expressed in healthy cells.
A type of morphea in which the lesions are circular or ovoid, and may be superficial or deep. The superficial lesions can have an indurated, waxy, ivory colored center with surrounding erythema or violaceous color during the active stage. Deep lesions can be sclerotic and depressed from underlying atrophy, and may show minimal skin color changes. When there are several (greater than or equal to 4), larger (greater than 3cm) lesions on two or more body areas this is classified as ""generalized morphea"".
A capsule-based formulation containing artificial bezoar, Strychni pulveratum (strychnos powder), camphol alcohol (borneol or borneo camphor) and extracts from Zedoary rhizome (Rhizoma curcumae), Pseudobulbus cremastrae seu pleiones (dried pseudobulb of Cremastra appendiculata), Yatantzu (seed of Brucca javanica), beehive, Bombyx mori (Bombyx batryticatus or silkworm), Danshen (dried root of Salvia miltiorrhiza or red sage root), Radix astragali, and Angelica, with potential antineoplastic activity. Upon oral administration of the cidan herbal capsule, the active ingredients in the plant extracts may induce tumor cell apoptosis and reduce tumor cell proliferation.
A lymphocytic inflammation of the uteroplacental vessels.
The presence of decidual plasma cells, scattered or in aggregate.
Increased parietal decidual lymphocytes invading the fetal chorion and/or amnion.
A focus of thrombus adhered to the wall of a fetal blood vessel in the chorionic plate.
A focus of thrombus adhered to the wall of a fetal blood vessel in the chorionic plate. It can be completely or partially obstructive and may lead to downstream villous injury and calcification.
A commercial combination preparation, by Biovail Pharmaceuticals, containing chlorpheniramine maleate, phenylephrine hydrochloride and methscopolamine nitrate used to relieve symptoms of cold and flu. Chlorpheniramine maleate, an antihistamine, blocks the effects of histamine, thereby preventing symptoms such as sneezing and itchy, watery eyes, runny nose and itchy throat. Phenylephrine hydrochloride, a sympathomimetic agent, acts as a decongestant by inducing blood vessels constriction mediated via alpha-adrenergic receptors, thereby reducing blood flow and decreasing swelling which prevents nasal and sinus congestion. Methscopolamine nitrate, an anticholinergic agent, may reduce fluid secretions and provides a drying effect in nose, eyes and chest.
A Hodgkin lymphoma with unfavorable prognosis that occurs during childhood.
An undifferentiated pleomorphic sarcoma that occurs during childhood.
A rare carcinoma of the thyroid gland that occurs during childhood.
A rare small cell carcinoma of the lung that occurs during childhood.
A rare carcinoma of the salivary gland that occurs during childhood.
A rare carcinoma of the rectum that occurs during childhood.
A protoplasmic astrocytoma that occurs during childhood.
A pleomorphic xanthoastrocytoma that occurs during childhood.
A pilomyxoid astrocytoma that occurs during childhood.
A rare carcinoma of the parathyroid gland that occurs during childhood.
A rare carcinoma of the paranasal sinus that occurs during childhood.
An oligoastrocytoma that occurs during childhood.
A rare non-small cell carcinoma of the lung that occurs during childhood.
A rare carcinoma of the nasal cavity that occurs during childhood.
A mixed glioma that occurs during childhood.
A rare malignant neoplasm of the penis that occurs during childhood.
A rare carcinoma of the larynx that occurs during childhood.
Langerhans cell histiocytosis that occurs during childhood.
An infectious disorder that occurs during infancy, childhood, or adolescence.
A germ cell tumor that arises from the testis or ovary and occurs during childhood.
A gliosarcoma that occurs during childhood.
A giant cell glioblastoma that occurs during childhood.
A gemistocytic astrocytoma that occurs during childhood.
A rare carcinoma of the stomach that occurs during childhood.
A fibrillary astrocytoma that occurs during childhood.
A Hodgkin lymphoma with favorable prognosis that occurs during childhood.
A rare carcinoma of the esophagus that occurs during childhood.
An epithelioid hemangioendothelioma that occurs during childhood.
An embryonal tumor with multilayered rosettes, C19MC-altered that occurs during childhood.
An ependymal tumor that occurs during childhood.
A diffuse astrocytoma that occurs during childhood.
A rare colorectal carcinoma that occurs during childhood.
A cerebral anaplastic astrocytoma that occurs during childhood.
A cerebellar anaplastic astrocytoma that occurs during childhood.
A central nervous system embryonal neoplasm that occurs during childhood.
A rare carcinoid tumor that occurs during childhood.
An oligodendroglioma that arises from the brain and occurs during childhood.
A rare carcinoma of the bladder that occurs during childhood.
An anaplastic oligoastrocytoma that occurs during childhood.
A rare pheochromocytoma of the adrenal gland that occurs during childhood.
An orally available, small molecule inhibitor of select serine-threonine kinases, including aurora kinase B (aurora B), vascular endothelial growth factor receptors (VEGFRs), stem cell factor receptor (c-KIT), and platelet-derived growth factor receptors (PDGFRs), with potential antineoplastic activity. Upon oral administration, chiauranib binds to and inhibits the activity of aurora B, VEGFRs, c-kit and PDGFRs, which may result in a decrease in the proliferation of tumor cells that overexpress these kinases. These kinases are overexpressed by a variety of cancer cell types.
A decoction of Liang Ge San, a traditional Chinese herbal medicine, with potential anti-inflammatory and anti-stomatitis activities. Although the complete mechanism of action through which the ChiNing decoction works has yet to be fully elucidated, upon oral administration, the active ingredients may inhibit the inflammatory response, possibly by reducing the levels of pro-inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNFa), in the saliva. This may protect the oral mucosa against these inflammatory mediators, and may reduce and relieve radiation-induced stomatitis and the associated pain.
The result or finding values as reported in a standard, character format.
Intracranial bleeding in the tissue of the cerebrum of a newborn infant occurring during labor and/or delivery.
A water-based, vaginal moisturizing gel containing a mixture of lambda- and kappa- carrageenans, sulfated polysaccharides derived from red seaweed (Chondrus crispus), with potential microbicidal activity against various viruses, including human papillomavirus (HPV), human immunodeficiencyvirus (HIV) and human herpes simplex virus (HSV). Upon vaginal insertion via an applicator, carrageenan specifically binds to the viral capsids, which prevents the binding of virions to heparan sulfate proteoglycan (HSPG) receptors or other, as of yet not fully identified, cellular proteins. In addition, the viral binding of carrageenan may also interfere with conformational changes within the virions after cellular attachment. This inhibits viral infection. Certain HPV types cause cervical cancer; therefore, the prevention of HPV infection by this gel may subsequently prevent the development of cervical cancer.
An osteosarcoma of mesenchymal origin in a dog. It is the most common bone cancer in dogs, most often developing in the limbs of large or giant breed dogs. The morphologic and biologic behavior of canine osteosarcomas is similar to that of human osteosarcomas.
Melanoma occurring in a dog. It is the most common malignant tumor found in the mouths of dogs and also occurs frequently on the digits. All canine melanomas are locally invasive and malignant canine melanomas show a high rate of metastasis. Melanoma in dogs has been established as a relevant model for human melanoma.
Kidney injury caused by calcineurin inhibitor immunosuppressive therapy which may lead to diminished kidney function.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with the human cytomegalovirus (CMV) phosphoprotein pp65, with potential immunostimulatory and antineoplastic activities. Upon administration, the CMV pp65 peptide-pulsed autologous DC vaccine exposes the immune system to the CMV pp65 peptide, which may result in a cytotoxic T-lymphocyte (CTL) response against CMV pp65-expressing tumor cells leading to cell lysis. The CMV pp65 protein, also called the 65 kDa lower matrix phosphoprotein, is the primary component of the enveloped subviral particle of CMV and is expressed in certain tumor types, such as glioblastoma.
Expression of a fusion protein that results from a t(10;19)(q26;q13) translocation, which involves the human genes CIC (capicua transcriptional suppressor) and DUX4L (double homeobox 4-like).
Expression of a fusion protein that results from a t(4;19)(q35;q13) translocation, which involves the human genes CIC (capicua transcriptional suppressor) and DUX4 (double homeobox 4).
An undifferentiated, high grade small round cell sarcoma affecting predominantly young adults. It is characterized by a recurrent translocation involving the CIC gene on chromosome 19 and either DUX4 gene on chromosome 4 or DUX4L gene on chromosome 10. The translocation results in either CIC-DUX4, t(4;19)(q35;q13) or CIC-DUX4L, t(10;19)(q26;q13) fusions.
Lack of production of functional C4 protein, due to a genetic defect requiring homozygous loss of both the C4A and C4B genetic paralogs. Approximately 75% of patients with a C4 deficiency will develop a severe systemic lupus erythematosus at an early age. Patients also present with frequent sinopulmonary infections often with Streptococcus pneumoniae.
A combination preparation containing the antihistamine brompheniramine maleate and phenylephrine hydrochloride used to relieve symptoms of the cold and allergy. Brompheniramine maleate blocks the effects of histamine, thereby preventing symptoms such as sneezing and itchy, watery eyes, runny nose and sore throat. Phenylephrine, a sympathomimetic agent, acts as a decongestant by inducing vasoconstriction mediated via alpha-adrenergic receptors. This reduces blood flow, decreases swelling and prevents nasal and sinus congestion.
A benzyl styryl sulfone analog, and a disodium phosphate ester prodrug of ON 013100, with potential antineoplastic activity. Upon hydrolysis, briciclib is converted to ON 013100, which blocks cyclin D mRNA translation and decreases protein expression of cyclin D. This may induce cell cycle arrest and apoptosis in cancer cells overexpressing cyclin D and eventually decrease tumor cell proliferation. This agent may exhibit synergistic antitumor activity in combination with other chemotherapeutic agents. Cyclin D, a member of the cyclin family of cell cycle regulators, plays a key role in cell cycle division and is often overexpressed in a variety of hematologic and solid tumors and is correlated with poor prognosis.
The outcome of the body weight assessment as originally received or collected.
The outcome of the body weight gain assessment as originally received or collected.
An indication or description of whether a body weight measurement was obtained from a subject that has abstained from food and possibly water for the prescribed amount of time.
The standard character or string for representation and reporting of body weight data.
An indication or description that body weight data is a baseline value.
Formulated for oral hygiene, Biotene Mouthwash contains antibacterial enzymes that boost natural salivary antibacterial defenses, protects teeth and gums, and provides relief or prevents dry mouth (xerostomia) induced by some drug therapies, as well as by acute renal failure, bone marrow transplant, hypertension, kidney dialysis, stroke, and radiation therapy. (NCI04)
An orally available inhibitor of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) with potential antineoplastic activity. Binimetinib, noncompetitive with ATP, binds to and inhibits the activity of MEK1/2. Inhibition of MEK1/2 prevents the activation of MEK1/2 dependent effector proteins and transcription factors, which may result in the inhibition of growth factor-mediated cell signaling. This may eventually lead to an inhibition of tumor cell proliferation and an inhibition in production of various inflammatory cytokines including interleukin-1, -6 and tumor necrosis factor. MEK1/2 are dual-specificity threonine/tyrosine kinases that play key roles in the activation of the RAS/RAF/MEK/ERK pathway and are often upregulated in a variety of tumor cell types.
A human monoclonal antibody directed against type II activin receptors (ActRII; ActR2), with potential muscle-sparing and anti-cachectic activities. Upon administration, bimagrumab binds to ActRII, which prevents the binding of the natural ligands, myostatin and activin, to activin receptors and blocks ActRII-mediated signaling. This increases protein synthesis, decreases protein degradation, stimulates skeletal muscle cell growth, and increases muscle function and strength. Overstimulation of the ActRII-mediated signaling pathway is associated with muscle loss and weakness.
Collections of degenerated nuclear fragments that are associated with tissue injury during placental abruption.
A vaccine composed of the bacteriophage phi X 174, a virus that infects the bacterium Escherichia coli (E. coli), that can be used as a diagnostic agent to measure immune function of immunocompromised patients. Upon administration of the bacteriophage phi X 174 vaccine, the bacteriophage may activate the immune system to induce bacteriophage phi X174 specific antibody responses. The clearance of phage from the blood and the measurement of phage neutralization by antibodies can be used to assess the immune status of patients with suspected antibody-mediated immunodeficiency and to measure the response to certain therapies.
A change in the amino acid sequence of the serine/threonine protein kinase B-raf protein where a threonine residue has been inserted between the threonine at position 599 and the valine at position 600.
A genetic variation where the trinucleotide, adenine-cytosine-adenine, has been inserted between the nucleotides at positions 1797 and 1798 of the coding sequence of the BRAF gene.
A genetic variation where the trinucleotide, thymine-adenine-cytosine, has been inserted between the nucleotides at positions 1796 and 1797 of the coding sequence of the BRAF gene.
End-stage hepatocellular carcinoma. Patients will receive symptomatic treatment. (HPB (Oxford) 2005; 7(1):35-41)
Advanced hepatocellular carcinoma. Patients may receive new agents in the setting of randomized controlled trials. (HPB (Oxford) 2005; 7(1):35-41)
Intermediate hepatocellular carcinoma. Patients may benefit from chemoembolization. (HPB (Oxford) 2005; 7(1):35-41)
Very early hepatocellular carcinoma. Patients are optimal candidates for resection. (HPB (Oxford) 2005; 7(1):35-41)
The maleate salt form of avitinib, an orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, avitinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the drug-resistant T790M EGFR mutant, which prevents signaling mediated by mutant forms of EGFR. This may both induce cell death and inhibit tumor growth in EGFR-mutated tumor cells. EGFR, a receptor tyrosine kinase that is mutated in a variety of cancers, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors, which also inhibit wild-type EGFR.
Focus of two or more placental terminal villi showing a total loss of villous capillaries and bland hyaline fibrosis of the villous stroma. Stromal karyorrhexis may or may not be evident.
An inherited disorder manifested only when two copies of a mutated gene are present.
An inherited disorder that manifests when one copy of a mutated gene is present.
A preparation of autologous, CD34-positive hematopoietic progenitor cells (HPCs) ex vivo transduced with TNS9.3.55, a lentiviral vector encoding the human beta-globin (hemoglobin-beta, HBB) gene, with potential to restore beta-globin expression and function. Autologous CD34-positive stem cells are isolated from the patient's own bone marrow, the deficient HBB gene is removed, and the cells are transduced with the lentiviral vector. Upon re-infusion of the TNS9.3.55-transduced CD34-positive cells back into the patient, these cells express beta-globin, thereby allowing the body to make normal hemoglobin and thus normal, healthy red blood cells. Beta-globin, the beta-chain of the most common form of hemoglobin, is encoded by the HBB gene; mutations in this gene prevent normal beta-globin production.
Autologous peripheral blood mononuclear cells (PBMCs) that are suspended in a solution containing the immunostimulant granulocyte-macrophage colony stimulating factor (GM-CSF).
A preparation of autologous CD8+ T-lymphocytes specifically reactive to the cancer-testis antigen NY-ESO-1, with potential immunostimulating and antineoplastic activities. Autologous NY-ESO-1-specific CD8+ T-lymphocytes were generated from T-cells isolated from a particular cancer patient, which were made specifically reactive to the NY-ESO-1 antigen, expanded ex vivo, and reintroduced into the patient. These tumor-reactive T-cells may stimulate a host immune response against tumor cells expressing the NY-ESO-1 antigen, resulting in tumor cell lysis. NY-ESO-1, an antigen found in normal testis, may be upregulated in various cancers.
A plasmid DNA vaccine encoding an autologous lymphoma-derived idiotype-targeting immunoglobulin (Ig)-derived single chain variable fragment (scFv) fused to the chemokine macrophage inflammatory protein 3 alpha (MIP3a), with potential immunostimulating and antineoplastic activities. Upon intramuscular vaccination, the autologous lymphoma immunoglobulin-derived scFv-chemokine DNA vaccine is taken up by antigen-presenting cells (APCs) and stimulates the immune system to exert a cytotoxic T-lymphocyte (CTL) response against the idiotype expressed on the surface of B lymphoma cells. MIP3a, also called chemokine (C-C motif) ligand 20 (CCL20), is a chemotactic cytokine able to enhance the immune response through binding to chemokine receptors expressed on APCs.
A cancer vaccine consisting of autologous, B-chronic lymphocytic leukemia (B-CLL) cells harvested from a patient and transduced ex vivo with an adenoviral vector encoding the gene for the human cytokine interleukin-2 (IL-2), with potential immunostimulating and antineoplastic activities. Upon reintroduction into the patient, the autologous IL-2-expressing B-CLL vaccine expresses IL-2, stimulates natural killer (NK) cells, and may enhance the cytotoxic T-lymphocyte (CTL) immune response against the patient's B-CLL cells.
A vaccine consisting of lethally irradiated human fetal lung fibroblasts (Medical Research Council 5 or MRC-5) transfected with autologous tumor DNA derived from a head and neck squamous cell carcinoma (HNSCC), with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the autologous HNSCC DNA-transfected semi-allogeneic fibroblasts MRC-5 vaccine expresses HNSCC tumor-associated antigens (TAAs), which may activate the immune system to induce a cytotoxic T-lymphocyte (CTL) response against HNSCC cells. The MRC-5 cell line, established in 1966, is a human diploid lung fibroblast cell line derived from the human lung tissue of a 14-week-old male fetus.
A cancer vaccine consisting of autologous, B-chronic lymphocytic leukemia (B-CLL) cells harvested from a patient and transduced with an adenoviral vector encoding the gene for the human CD40 ligand (CD40L; TRAP; CD154), with potential immunostimulating and antineoplastic activities. Upon reintroduction into the patient, the autologous CD40L-expressing B-CLL vaccine expresses the co-stimulatory molecule CD40L, which binds to its cognate receptor, CD40, on antigen presenting cells (APC). This induces apoptosis, stimulates maturation and proliferation of APCs, and facilitates a cytotoxic T-lymphocyte (CTL) response against tumor cells. CD40L is a type II membrane protein that binds to CD40, which is a cell surface receptor that belongs to the tumor necrosis factor (TNF) receptor superfamily.
A preparation of genetically modified CD8+ central memory (Tcm) and CD4+ autologous T-lymphocytes (1:1) transduced with a replication incompetent, self-inactivating (SIN) lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-CD19 single chain variable fragment (scFv) derived from the murine IgG1 monoclonal antibody (mAb) FMC63, fused to the signaling domain of 4-1BB (CD137), the zeta chain of the TCR/CD3 complex (CD3-zeta), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, autologous anti-CD19CAR-4-1BB-CD3zeta-EGFRt-expressing T lymphocytes are directed to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity response. The 4-1BB costimulatory signaling domain enhances both proliferation of T-cells and antitumor activity.
An electrocardiographic recording that demonstrates atrial tachycardia without 1:1 atrioventricular conduction.
A response indicating that something occurs with the same frequency or intensity as previously.
Placental villous microscopic features that are typical for the gestational age at birth.
An orally available capsule containing antroquinonol, a farnesylated quinone derivative isolated from the mycelium of Antrodia camphorata, with potential antineoplastic activity. Upon oral administration, antroquinonol binds to and inhibits protein prenylation mediated by the enzymes farnesyltransferase (FTase) and geranylgeranyltransferase 1 (GGTase-1). This prevents both post-translational prenylation and signaling activity of a number of Ras superfamily proteins, such as Ras and Rho. This results in the inhibition of downstream signaling, such as the PI3K/mTOR signaling pathway, and induces apoptosis in susceptible tumor cells. Ras superfamily proteins are overexpressed in numerous cancer cell types, and play a key role in tumor cell proliferation and survival.
An individualized, therapeutic cancer vaccine (IVAC) composed of liposomes containing RNA encoding two or three tumor associated antigens (TAAs) that are specifically expressed in the patient's individual cancer selected from a warehouse (""off the shelf"") and p53 RNA, with potential immunostimulatory and antineoplastic activities. Upon administration, the antigen-targeted personalized breast cancer vaccines are translated by antigen presenting cells (APCs) and the expressed protein is presented via major histocompatibility complex (MHC) molecules on the surface of the APCs. This leads to an induction of both cytotoxic T-lymphocyte (CTL) and memory T-cell immune responses against the TAAs. The RNAs in the vaccine are specifically selected for an individual patient after RNA profiling of the patient's tumor.
A brand of combination medications, by Wyeth Pharmaceuticals, used in the treatment of hemorrhoids. Preparation H is used to relieve pain, swelling and pruritis, as well as, to soothe and protect the hemorrhoidal tissue. Preparation H products are formulated as a cream, ointment, cooling gel, suppositories and witch hazel wipes.
A condition of the newborn characterized by the destruction of red blood cells initiated by the transmission of antibodies from a mother to the child via the placenta against the D antigen, the most common Rhesus factor.
A corn-based, water-soluble extract rich in the polyphenol anthocyanin, with potential antioxidant, anti-inflammatory and chemoprotective activities. Upon administration of the anthocyanin-rich corn extract, the anthocyanins scavenge reactive oxygen species (ROS), which protects healthy cells from radiation-induced oxidative stress and DNA damage. In addition, anthocyanins modulate the expression of various genes and proteins involved in inflammation, tumor cell proliferation, angiogenesis, tumor cell invasion and differentiation. This agent also chelates metals and induces the expression of enzymes involved in Phase II antioxidant and detoxification pathways, which may further protect cells against oxidative stress induced by toxins and carcinogens.
A prolonged-release tablet formulation containing the quinazoline anagrelide, with antiplatelet activity. Although the exact mechanism of action through which anagrelide exerts its effect has yet to be fully elucidated, this agent inhibits the maturation of megakaryocytes into platelets, which reduces platelet production. Anagrelide also inhibits cyclic AMP phosphodiesterase III (PDEIII), which prevents PDEIII-mediated platelet aggregation. This may prevent essential thrombocythemia and thrombosis.
Lack of drive to participate in social activities or goal oriented behavior.
Loss of the amnionic epithelial surface.
An orally bioavailable inhibitor of c-Met/hepatocyte growth factor receptor (HGFR), vascular endothelial growth factor receptor type 2 (VEGFR2), Tie2 receptor tyrosine kinase (TIE2), and tropomyosin receptor kinase (Trk), with potential antiangiogenic and antineoplastic activities. Upon administration, altiratinib selectively binds to c-Met, VEGFR2, Tie2 and Trk tyrosine kinases, which may lead to the inhibition of endothelial cell migration, proliferation and survival. This also results in both an inhibition of tumor cell proliferation and increased tumor cell death in c-Met/VEGFR2/Tie2/Trk-expressing cells. These receptor tyrosine kinases (RTKs), frequently overexpressed or mutated by a variety of tumor cell types, play crucial roles in the regulation of angiogenesis, tumor cell growth and survival.
Thrombus formation within the arterial or venous system of donor tissue post transplantation.
A Hodgkin lymphoma with unfavorable prognosis that occurs during adulthood.
A carcinoma of the salivary gland that occurs during adulthood.
A pleomorphic hepatocellular carcinoma that occurs during adulthood.
A pineal gland astrocytoma that occurs during adulthood.
A carcinoma of the penis that occurs during adulthood.
Myelodysplastic syndrome that occurs in adulthood.
A mixed glioma that occurs during adulthood.
Langerhans cell histiocytosis that occurs during adulthood.
A germ cell tumor that occurs during adulthood.
A hepatocellular carcinoma, fibrolamellar variant that occurs during adulthood.
A Hodgkin lymphoma with favorable prognosis that occurs during adulthood.
An epithelioid hemangioendothelioma that occurs during adulthood.
A combined hepatocellular carcinoma and cholangiocarcinoma that occurs during adulthood.
A B-cell acute leukemia that occurs during adulthood. It is characterized by the presence of lymphoblasts that carry a translocation between the BCR gene on chromosome 22 and the ABL1 gene on chromosome 9. It results in the production of the p190 kd or p210 kd fusion protein. It has an unfavorable clinical outcome.
A focus of necrotic placental parenchyma with clearly visible outlines of necrotic villous structures and absence of any hyalinization and fibrosis, which is frequently 1-2 days of duration.
An electrocardiographic finding assessment of new or presumed new significant ST-segment-T wave (ST-T) changes or new left bundle branch block consistent with acute myocardial ischemia. (Thygesen K, Alpert JS, Jaffe AS, et al.: the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. J Am Coll Cardiol 60(16):1-18, 2012)
A motor sensory axonal form of Guillain-Barré syndrome. Patients present with muscle weakness and sensory deficits, similar to that of the more frequent demyelinating form of Guillain-Barré syndrome. As in other types of Guillain-Barré syndrome, an infectious disease precedes the onset of limb weakness in the majority of cases. Although the exact pathological mechanism is poorly understood the disease is associated with the presence of antiganglioside antibodies and may be caused by antibody-mediated primary axonal degeneration or antibody-mediated inhibition of voltage-gated sodium channels.
A sentinel hypoxic event occurring during labor, with evidence of fetal metabolic acidosis in the fetal umbilical arterial blood; a sudden and sustained fetal bradycardia or the absence of fetal heart rate variability in the presence of persistent, late, or variable decelerations (category III tracing); previously normal Apgar scores that are 0-3 beyond 5 minutes.
A focus of maternal thrombus within the placental intervillous space, often with peripheral villous compression, which is less than 1-2 days in age.
A sudden onset of B-cell mediated immune response occurring after transplantation, directed against donor kidney alloantigens.
A sudden onset of T-cell mediated immune response occurring after transplantation, directed against donor kidney alloantigens.
Growth hormone deficiency that is not present at birth; this condition may result from a variety of causes such as intracranial tumors or their treatment, infection, trauma or other cause.
A condition characterized by reduced or absent movement of the ipsilateral face as a consequence of an injury to the seventh cranial nerve that has occurred after birth.
A commercial combination preparation, by Johnson and Johnson, containing acetaminophen and pseudoephedrine hydrochloride used to relieve symptoms of cold and flu. Acetaminophen exerts analgesic and antipyretic actions by inhibiting prostaglandin synthesis. Pseudoephedrine hydrochloride, a sympathomimetic agent, acts as a decongestant by inducing vasoconstriction mediated through alpha-adrenergic receptors, thereby reducing blood flow which decreases swelling and prevents and relieves nasal and sinus congestion.
A combination preparation containing the analgesic acetaminophen and a combination of one or more of the following agents: an antihistamine (chlorpheniramine maleate or brompheniramine maleate), the expectorant guaifenesin, the antitussive dextromethorphan maleate and/or the decongestant pseudoephedrine hydrochloride or phenylephrine hydrochloride. These preparations are used to relieve symptoms of cold, cough and flu.
Placental villous histology not typical of gestational age, with features of more mature villi.
Failure of the maternal spiral arteries to be transformed by extravillous cytotrophoblast to increase blood flow into the placental intervillous spaces, which may lead to an increased risk of early-onset pre-eclampsia and fetal growth restriction.
An electrocardiographic finding of abnormal QRS complex(es) that are supraventricular in origin, and that are wide secondary to aberrant AV conduction. (CDISC)
Inadequate development of an arteriovenous fistula within three months of creation.
An orally bioavailable small molecule, with potential antineoplastic activity.
A proprietary antibody that targets the complement inflammatory pathway with potential immunomodulating and anti-inflammatory activities. Upon intravenous administration, anti-inflammatory antibody ALXN1007 modulates the complement inflammatory pathway through binding to an as of yet undisclosed target. This may help in the treatment of certain inflammatory-mediated disorders, such as antiphospholipid syndrome (APS). This agent may also influence the progression of graft-versus-host disease (GvHD).
An electrocardiographic finding, in the absence of left ventricular hypertrophy (LVH) and left bundle branch block pattern on ECG, of either a) new (or presumed new) ST elevation at the J point in two contiguous leads with the following cut-points: greater than or equal to 0.1 mV in all leads other than leads V2-V3 where the following cut points apply: greater than or equal to 0.2 mV in men age greater than or equal to 40 years, greater than or equal to 0.25 mV in men age greater than 40 years, or greater than or equal to 0.15 mV in women; or b) new (or presumed new) horizontal or down-sloping ST depression greater than or equal to 0.05 mV in two contiguous leads, and/or T wave inversion greater than or equal to 0.1 mV in two contiguous leads with a prominent R wave, or R/S ratio greater than 1. (Thygesen K, Alpert JS, Jaffe AS, et al.: the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. J Am Coll Cardiol 60(16):1-18, 2012)
Conditions in 46,XY individuals in which androgens are produced in typical amounts, but tissue response to androgens is reduced.
Hypoplastic amelogenesis imperfecta IA is characterized by enamel that may not develop to normal thickness. The enamel may have pits on the labial or buccal surfaces that are often arranged in rows and columns (see Witkop, 1989).
Tubular aggregates in muscle, first described by Engel (1964), are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They are a nonspecific pathologic finding that may occur in a variety of circumstances, including alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness, and inherited myopathies. Tubular aggregates are derived from the sarcoplasmic reticulum (Salviati et al., 1985) and are believed to represent an adaptive mechanism aimed at regulating an increased intracellular level of calcium in order to prevent the muscle fibers from hypercontraction and necrosis (Martin et al., 1997; Muller et al., 2001). Genetic Heterogeneity of Tubular Aggregate Myopathy See also TAM2 (615883), caused by mutation in the ORAI1 gene (610277) on chromosome 12q24.
A form of frontotemporal dementia characterised by progressive behavioural impairment and a decline in executive function with frontal lobe-predominant atrophy.
White sponge nevus is a rare autosomal dominant disorder of noncornifying squamous epithelial differentiation that presents clinically as white, soft, thick plaques of the oral mucosa. Less frequently, the mucous membranes of the nose, esophagus, genitalia, and rectum are involved. Histopathologic features, including epithelial thickening, parakeratosis, extensive vacuolization of the suprabasal keratinocytes, and compact aggregates of keratin intermediate filaments in the upper spinus layers resemble those found in epidermal disorders shown to be associated with keratin defects (summary by Richard et al., 1995). Genetic Heterogeneity of White Sponge Nevus White sponge nevus-2 (WSN2; 615785) is caused by mutation in the KRT13 gene (148065) on chromosome 17q21.
Immunodeficiency-27A results from autosomal recessive (AR) IFNGR1 deficiency. Patients with complete IFNGR1 deficiency have a severe clinical phenotype characterized by early and often fatal mycobacterial infections. bacillus Calmette-Guerin (BCG) and environmental mycobacteria are the most frequent pathogens, and infection typically begins before the age of 3 years. Plasma from patients with complete AR IFNGR1 deficiency usually contains large amounts of IFNG (147570), and their cells do not respond to IFNG in vitro. In contrast, cells from patients with partial AR IFNGR1 deficiency, which is caused by a specific mutation in IFNGR1, retain residual responses to high IFNG concentrations. Patients with partial AR IFNGR1 deficiency are susceptible to BCG and environmental mycobacteria, but they have a milder clinical disease and better prognosis than patients with complete AR IFNGR1 deficiency. The clinical features of children with complete AR IFNGR1 deficiency are usually more severe than those in individuals with AD IFNGR1 deficiency (IMD27B), and mycobacterial infection often occurs earlier (mean age of 1.3 years vs 13.4 years), with patients having shorter mean disease-free survival. Salmonellosis is present in about 5% of patients with AR or AD IFNGR1 deficiency, and other infections have been reported in single patients (review by Al-Muhsen and Casanova, 2008).
Coloboma is an ocular birth defect resulting from abnormal development of the eye during embryogenesis. It is defined as a congenital defect in any ocular tissue, typically presenting as absent tissue or a gap, at a site consistent with aberrant closure of the optic fissure. Failure of fusion can lead to coloboma of 1 or multiple regions of the inferior portion of the eye affecting any part of the globe traversed by the fissure, from the iris to the optic nerve, including the ciliary body, retina, and choroid. Coloboma is also frequently associated with small (microphthalmic) or absent (anophthalmic) eyes as part of an interrelated spectrum of developmental eye anomalies, and can affect either one or both eyes (summary by Kelberman et al., 2014). For a discussion of genetic heterogeneity of ocular coloboma, see 120200.
Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by generalized lymphatic dysplasia affecting various organs, including the intestinal tract, pericardium, and limbs. Additional features of the disorder include facial dysmorphism and cognitive impairment (summary by Alders et al., 2014). Genetic Heterogeneity of Hennekam Lymphangiectasia-Lymphedema Syndrome See also HKLLS2 (616006), caused by mutation in the FAT4 gene (612411) on chromosome 4q28, and HKLLS3 (618154), caused by mutation in the ADAMTS3 gene (605011) on chromosome 4q13.
Desbuquois dysplasia (DBQD) is an autosomal recessive chondrodysplasia belonging to the multiple dislocation group and characterized by severe prenatal and postnatal growth retardation (stature less than -5 SD), joint laxity, short extremities, and progressive scoliosis. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advanced carpal and tarsal bone age with a delta phalanx (summary by Huber et al., 2009). Desbuquois dysplasia is clinically and radiographically heterogeneous, and had been classified into 2 types based on the presence (type 1) or absence (type 2) of characteristic hand anomalies, including an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and dislocation of the interphalangeal joints (Faivre et al., 2004). However, patients with and without these additional hand anomalies have been reported to have mutations in the same gene (see, e.g., CANT1); thus, these features are not distinctive criteria to predict the molecular basis of DBQD (Furuichi et al., 2011). In addition, Kim et al. (2010) described another milder variant of DBQD with almost normal outwardly appearing hands, but significant radiographic changes, including short metacarpals, elongated phalanges, and remarkably advanced carpal bone age. However, there is no accessory ossification center distal to the second metacarpal, and patients do not have thumb anomalies. Similar changes occur in the feet. These patients also tend to develop precocious osteoarthritis of the hand and spine with age. This phenotype is sometimes referred to as the 'Kim variant' of DBQD (Furuichi et al., 2011). Genetic Heterogeneity of Desbuquois Dysplasia DBQD2 (615777) is caused by mutation in the XYLT1 gene (608124) on chromosome 16p12. Two unrelated patients with immunodeficiency-23 (IMD23; 615816), due to mutation in the PGM3 gene (172100), were reported to have skeletal features reminiscent of DBQD.
Tetraamelia syndrome-1 is characterized by complete limb agenesis without defects of scapulae or clavicles. Other features include bilateral cleft lip/palate, diaphragmatic defect with bilobar right lung, renal and adrenal agenesis, pelvic hypoplasia, and urogenital defects (Niemann et al., 2004). Genetic Heterogeneity of tetraamelia syndrome Tetraamelia syndrome-2 (TETAMS2; 618021) is caused by mutation in the RSPO2 gene (610575) on chromosome 8q23.
An abnormal conical form of the teeth, that is, a tooth whose sides converge or taper together incisally.
A form of congenital disorders of N-linked glycosylation with characteristics of neurologic abnormalities (global developmental delay in language, social skills and fine and gross motor development, intellectual disability, hypotonia, microcephaly, seizures/epilepsy), facial dysmorphism (deep set eyes, large ears, hypoplastic vermillion of upper lip, large mouth with widely spaced teeth), feeding problems often due to chewing difficulties and aversion to food with certain textures, failure to thrive, gastrointestinal abnormalities (reflux or vomiting) and strabismus. The disease is caused by mutations in the gene SSR4 (Xq28).
The MPPH syndrome is a developmental brain disorder characterized by megalencephaly (brain overgrowth) with the cortical malformation bilateral perisylvian polymicrogyria (BPP). At birth the occipital frontal circumference (OFC) ranges from normal to 6 standard deviations (SD) above the mean for age, sex, and gestational age; in older individuals the range is from 3 to 10 SD above the mean. A variable degree of ventriculomegaly is seen in almost all children with MPPH syndrome; nearly 50% of those have frank hydrocephalus. Neurologic problems associated with BPP include oromotor dysfunction (100%), epilepsy (50%), and mild to severe intellectual disability (100%). Postaxial hexadactyly occurs in 50% of individuals with MPPH syndrome.
Ataxia-telangiectasia-like disorder-1 is an autosomal recessive disorder characterized clinically by progressive cerebellar degeneration resulting in ataxia and oculomotor apraxia. Laboratory studies of patient cells showed increased susceptibility to radiation, consistent with a defect in DNA repair. The disorder shares some phenotypic features of ataxia-telangiectasia (AT; 208900), but telangiectases and immune deficiency are not present in ATLD1 (summary by Hernandez et al., 1993 and Stewart et al., 1999). Genetic Heterogeneity of Ataxia-Telangiectasia-Like Disorder See also ATLD2 (615919), caused by mutation in the PCNA gene (176740) on chromosome 20p12.
A mild delay in the achievement of motor or mental milestones in the domains of development of a child. [DDD:hvfirth]
Giant axonal neuropathy-2 is an autosomal dominant peripheral axonal neuropathy characterized by onset of distal sensory impairment and lower extremity muscle weakness and atrophy after the second decade. Foot deformities may be present in childhood. More severely affected individuals may develop cardiomyopathy. Sural nerve biopsy shows giant axonal swelling with neurofilament accumulation (summary by Klein et al., 2014).
A malignant, high grade neuroendocrine neoplasm that arises from the cervix. This category includes small cell and large cell neuroendocrine carcinoma.
Decreased posterolateral protrusion of the tragus.
Childhood absence epilepsy and juvenile myoclonic epilepsy are both subtypes of what has classically been called idiopathic generalized epilepsy (IGE, EIG; see 600669). For a phenotypic description and a discussion of genetic heterogeneity of idiopathic generalized epilepsy, see 600669. For a phenotypic description and a discussion of genetic heterogeneity of juvenile myoclonic epilepsy and childhood absence epilepsy, see ECA1 (600131) and JME (254770), respectively.
Mental retardation with language impairment and with or without autistic features is a neurodevelopmental disorder characterized by global developmental delay with moderate to severe speech delay that particularly affects expressive speech. Most patients have articulation defects, but frank verbal dyspraxia is not observed. Common dysmorphic features include broad forehead, downslanting palpebral fissures, short nose with broad tip, relative macrocephaly, frontal hair upsweep, and prominent digit pads. Gross motor skills are also delayed. Some patients have autistic features and/or behavioral problems. All reported cases have occurred de novo (review by Le Fevre et al., 2013).
IMD28 is caused by autosomal recessive (AR) IFNGR2 deficiency, a rare molecular cause of susceptibility to mycobacterial disease. The clinical presentation of complete AR IFNGR2 deficiency resembles that of complete IFNGR1 deficiency (IMD27A; 209950). The disease manifests early in life, with severe, often fatal, infection. The most commonly encountered pathogens include M. bovis bacillus Calmette-Guerin (BCG), M. avium, and M. fortuitum. Complete AR IFNGR2 deficiency is characterized by an undetectable cellular response to interferon-gamma (IFNG; 147570). There is also a rare, partial form of AR IFNGR2 deficiency, reported in 1 child, who retained a residual cellular response to IFNG and presented with a relatively mild infection by M. bovis BCG and M. abscessus (review by Al-Muhsen and Casanova, 2008).
IMD29 results from autosomal recessive IL12B deficiency and is characterized by undetectable IL12B secretion from leukocytes. IL12B-deficient patients generally present with bacillus Calmette-Guerin (BCG) disease after vaccination in childhood, and at least half also have Salmonella infection. Infections with Mycobacterium tuberculosis and environmental mycobacteria have also been reported in IL12B-deficient patients. The phenotype is relatively mild, and patients have a good prognosis (review by Al-Muhsen and Casanova, 2008).
IMD30 results from autosomal recessive IL12RB1 deficiency and is the most common form of susceptibility to mycobacterial disease. Activated T and natural killer lymphocytes from IMD30 patients do not express IL12RB1 on their surface or, more rarely, express nonfunctional IL12RB1 on their surface. IMD30 patients therefore lack responses to IL12 (see 161560) and IL23 (see 605580). The clinical presentation of IL12RB1-deficient patients is similar to that of IL12B-deficient patients (see IMD29, 614890). Bacillus Calmette-Guerin (BCG) disease and salmonellosis are the most frequent infections. Salmonellosis is present in about half of IL12RB1-deficient patients, and significant numbers of patients present with isolated salmonellosis. Severe tuberculosis has been reported in several unrelated patients, and other infections have been reported in single patients. IMD30 has low penetrance, and patients have relatively mild disease and good prognosis (review by Al-Muhsen and Casanova, 2008).
IMD31A results from autosomal dominant (AD) STAT1 deficiency. STAT1 is crucial for cellular responses to IFNA (147660)/IFNB (147640) (type I interferon) and IFNG (147570) (type III interferon). AD STAT1 deficiency selectively affects the IFNG pathway, but not the IFNA/IFNB pathway, and confers a predisposition to mycobacterial infections. Pathogens reported in IMD31A patients include bacillus Calmette-Guerin (BCG) and Mycobacterium avium complex, as well as Mycobacterium tuberculosis. IMD31A has low penetrance and a mild clinical phenotype with good prognosis for recovery (review by Al-Muhsen and Casanova, 2008). Two patients with heterozygous STAT1 mutations have been reported with increased susceptibility to adult-onset herpes simplex encephalitis (HSE) without a history of other significant infections (Mork et al., 2015).
Progressive microcephaly with seizures and cerebral and cerebellar atrophy is a severe autosomal recessive neurodevelopmental and neurodegenerative disorder with onset in the first days or months of life. Patients are born with microcephaly and soon develop intractable seizures, resulting in profoundly delayed development and hypotonia (summary by Zhang et al., 2014).
Autosomal recessive spinocerebellar ataxia-16 is a progressive neurologic disorder characterized by truncal and limb ataxia resulting in gait instability. Most patients have onset in the teenage years, although earlier and later onset have been reported. Additional features may include dysarthria, nystagmus, spasticity of the lower limbs, and mild peripheral sensory neuropathy (summary by Shi et al., 2013).
Atrial fibrillation (AF) is a supraventricular tachyarrhythmia characterized by uncoordinated atrial activation with consequent deterioration of atrial mechanical function. It is the most common sustained cardiac rhythm disturbance, and its prevalence increases as the population ages. An estimated 70,000 strokes each year are caused by atrial fibrillation (summary by Oberti et al., 2004). For a discussion of genetic heterogeneity of atrial fibrillation, see 608583.
Desbuquois dysplasia, which belongs to the multiple dislocation group of disorders, is characterized by dislocations of large joints, severe pre- and postnatal growth retardation, joint laxity, and flat face with prominent eyes. Radiologic features include short long bones with an exaggerated trochanter that gives a 'monkey wrench' appearance to the proximal femur, and advanced carpal and tarsal ossification (summary by Bui et al., 2014). For a discussion of genetic heterogeneity of Desbuquois dysplasia, see DBQD1 (251450).
Retinitis pigmentosa (RP), also designated rod-cone dystrophy, is characterized by initial night blindness due to rod dysfunction, with subsequent progressive constriction of visual fields, abnormal color vision, and eventual loss of central vision due to cone photoreceptor involvement (summary by El Shamieh et al., 2014). For a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
White sponge nevus is a condition characterized by the formation of white patches of tissue called nevi (singular: nevus) that appear as thickened, velvety, sponge-like tissue. The nevi are most commonly found on the moist lining of the mouth (oral mucosa), especially on the inside of the cheeks (buccal mucosa). Affected individuals usually develop multiple nevi. Rarely, white sponge nevi also occur on the mucosae (singular: mucosa) of the nose, esophagus, genitals, or anus. The nevi are caused by a noncancerous (benign) overgrowth of cells.White sponge nevus can be present from birth but usually first appears during early childhood. The size and location of the nevi can change over time. In the oral mucosa, both sides of the mouth are usually affected. The nevi are generally painless, but the folds of extra tissue can promote bacterial growth, which can lead to infection that may cause discomfort. The altered texture and appearance of the affected tissue, especially the oral mucosa, can be bothersome for some affected individuals.
Short stature with microcephaly and distinctive facies is characterized by pre- or postnatal growth retardation, frontal bossing, high forehead, sparse hair and eyebrows, and telecanthus. Patients also show skin dyspigmentation, with hyper- and/or hypopigmented areas (Leduc et al., 2016).
Autosomal recessive mental retardation-42 is a neurodevelopmental disorder characterized by severely delayed psychomotor development. Additional features are variable and include nonspecific dysmorphic facial features, hypotonia, structural brain abnormalities, and cortical visual impairment (summary by Bosch et al., 2015). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Pontocerebellar hypoplasia type 10 is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy and delayed myelination. Some patients have dysmorphic features and an axonal sensorimotor neuropathy (summary by Karaca et al., 2014 and Schaffer et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
Pontocerebellar hypoplasia type 9 is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by severely delayed psychomotor development, progressive microcephaly, spasticity, seizures, and brain abnormalities, including brain atrophy, thin corpus callosum, and delayed myelination (summary by Akizu et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
IMD23 is an autosomal recessive primary immunodeficiency syndrome characterized by recurrent respiratory and skin infections beginning in early childhood. Laboratory studies are notable for increased serum IgE. Affected individuals also show developmental delay or cognitive impairment of varying severity (summary by Zhang et al., 2014).
Xia-Gibbs syndrome is a neurological disorder characterized by weak muscle tone (hypotonia), mild to severe intellectual disability and delayed development. Expressive language skills (vocabulary and the production of speech) are particularly affected; children with this condition usually do not speak their first word, a milestone typically achieved within the first year, until age two or later, and some never learn to talk. Development of motor skills, such as crawling and walking, can also be delayed.Other signs and symptoms of Xia-Gibbs syndrome vary among affected individuals. Additional neurological features include poor coordination and balance (ataxia) and seizures. Feeding problems and sleep abnormalities can also occur in people with the condition, and many affected individuals experience short pauses in breathing while they sleep (obstructive sleep apnea). In some people with Xia-Gibbs syndrome, imaging tests of the brain show abnormalities in the brain's structure. For example, the tissue connecting the left and right halves of the brain (the corpus callosum) can be abnormally thin.Xia-Gibbs syndrome can also affect physical development. Growth is usually impaired, and many affected individuals are shorter than their peers. Side-to-side curvature of the spine (scoliosis) is also a common feature. Some people with Xia-Gibbs syndrome have unusual facial features, such as a broad forehead, low-set ears or ears that stick out, widely space eyes (hypertelorism), eye openings that slant up or down (upslanting palpebral fissures or downslanting palpebral fissures), a flat bridge of the nose, or a thin upper lip. Other, less-common abnormalities involving the bones and skin include premature fusion of certain skull bones (craniosynostosis), unusually loose (lax) joints, and loose skin.Behavior problems can also occur in Xia-Gibbs syndrome. Some affected individuals have features of autism spectrum disorder, which is characterized by impaired communication and social interactions, or of attention deficit hyperactivity disorder (ADHD). Other problems can include aggression, anxiety, poor impulse control, and self-injury.
Cushing syndrome is a clinical designation for the systemic signs and symptoms arising from excess cortisol production. Affected individuals typically show hypertension, impaired glucose tolerance, central obesity, osteoporosis, and sometimes depression. Corticotropin-independent Cushing syndrome results from autonomous cortisol production by the adrenal glands, often associated with adrenocortical tumors. Adrenocortical tumors are most common in adult females (summary by Cao et al., 2014; Sato et al., 2014).
Mitochondrial complex III deficiency, nuclear type 8, is an autosomal recessive disorder characterized by progressive neurodegeneration with onset in childhood. Affected individuals may have normal or delayed early development, and often have episodic acute neurologic decompensation and regression associated with febrile illnesses. The developmental regression results in variable intellectual disability and motor deficits, such as hypotonia, axial hypertonia, and spasticity; some patients may lose the ability to walk independently. Laboratory studies show increased serum lactate and isolated deficiency of mitochondrial complex III in skeletal muscle and fibroblasts. Brain imaging shows a characteristic pattern of multifocal small cystic lesions in the periventricular and deep cerebral white matter (summary by Dallabona et al., 2016). For a discussion of genetic heterogeneity of mitochondrial complex III deficiency, see MC3DN1 (124000).
Pontocerebellar hypoplasia type 2E is an autosomal recessive neurodegenerative disorder characterized by profound mental retardation, progressive microcephaly, spasticity, and early-onset epilepsy (summary by Feinstein et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (277470).
ADNP-related intellectual disability and autism spectrum disorders (ADNP-related ID/ASD) are characterized by mild to severe intellectual disability and autism spectrum disorder (ASD). Of the 24 individuals reported to date, 23 were ascertained in cohorts with autism spectrum disorder (ASD) / intellectual disability (ID); one was identified in a clinical setting. The clinical information available on 12 of the 24 revealed: delayed developmental milestones (walking independently between 19 months and 4.5 years) and speech ranging from no words to sentences. ASD was characterized by stereotypic behavior and impaired social interaction. Other common findings include behavioral problems, sleep disturbance, hypotonia, seizures, feeding difficulties, visual problems (hypermetropia, strabismus, cortical visual impairment), and cardiac defects.
Tatton-Brown-Rahman syndrome is characterized by tall stature, a distinctive facial appearance, and intellectual disability (Tatton-Brown et al., 2014).
Autosomal recessive amelogenesis imperfecta of the pigmented hypomaturation type is characterized by enamel of normal thickness that is hypomineralized and has a mottled appearance. The slightly soft enamel detaches easily from the dentin, and radiographs show a lack of contrast between enamel and dentin (Witkop, 1989).
Progressive leukoencephalopathy with ovarian failure is an autosomal recessive neurodegenerative disorder characterized by loss of motor and cognitive skills, usually with onset in young adulthood. Some patients may have a history of delayed motor development or learning difficulties in early childhood. Neurologic decline is severe, usually resulting in gait difficulties, ataxia, spasticity, and cognitive decline and dementia. Most patients lose speech and become wheelchair-bound or bedridden. Brain MRI shows progressive white matter signal abnormalities in the deep white matter. Affected females develop premature ovarian failure (summary by Dallabona et al., 2014).
Polyglucosan body myopathy-1 is an autosomal recessive disorder characterized by onset in childhood of progressive proximal muscle weakness, resulting in difficulties in ambulation. Most patients also develop progressive dilated cardiomyopathy, which may necessitate cardiac transplant in severe cases. A small subset of patients present with severe immunodeficiency and a hyperinflammatory state in very early childhood (summary by Boisson et al., 2012 and Nilsson et al., 2013). Genetic Heterogeneity of Polyglucosan Body Myopathy See also PGBM2 (616199), caused by mutation in the GYG1 gene (603942) on chromosome 3q24.
IMD24 is an autosomal recessive immunodeficiency characterized by the impaired capacity of activated T and B cells to proliferate in response to antigen receptor-mediated activation. Patients have early onset of severe chronic viral infections, mostly caused by herpesviruses, including Epstein-Barr virus (EBV) and varicella zoster virus (VZV); they also suffer from recurrent encapsulated bacterial infections, a spectrum typical of a combined deficiency of adaptive immunity (CID) (summary by Martin et al., 2014).
Any structural anomaly of the mitochondria.
Ataxia-telangiectasia-like disorder-2 is an autosomal recessive syndrome resulting from defects in DNA excision repair. Affected individuals have a neurodegenerative phenotype characterized by developmental delay, ataxia, and sensorineural hearing loss. Other features include short stature, cutaneous and ocular telangiectasia, and photosensitivity (summary by Baple et al., 2014). For a discussion of genetic heterogeneity of ATLD, see ATLD1 (604391).
The spectrum of BSCL2-related neurologic disorders includes Silver syndrome and variants of Charcot-Marie-Tooth neuropathy type 2, distal hereditary motor neuropathy (dHMN) type V, and spastic paraplegia 17. Features of these disorders include onset of symptoms ranging from the first to the seventh decade, slow disease progression, upper motor neuron involvement (gait disturbance with pyramidal signs ranging from mild to severe spasticity with hyperreflexia in the lower limbs and variable extensor plantar responses), lower motor neuron involvement (amyotrophy of the peroneal muscles and small muscles of the hand), and pes cavus and other foot deformities. Disease severity is variable among and within families.
Webb-Dattani syndrome is an autosomal recessive disorder characterized by frontotemporal hypoplasia, globally delayed development, and pituitary and hypothalamic insufficiency due to hypoplastic development of these brain regions. Patients present soon after birth with multiple pituitary hormonal deficiencies and subsequently develop microcephaly, seizures, and spasticity. Other features include postretinal blindness and renal abnormalities (summary by Webb et al., 2013).
STING-associated vasculopathy with onset in infancy is an autoinflammatory vasculopathy causing severe skin lesions, particularly affecting the face, ears, nose, and digits, and resulting in ulceration, eschar formation, necrosis, and, in some cases, amputation. Many patients have interstitial lung disease. Tissue biopsy and laboratory findings show a hyperinflammatory state, with evidence of increased beta-interferon (IFNB1; 147640) signaling (summary by Liu et al., 2014).
Lymphadenopathy (enlargement of lymph nodes) owing to hyperplasia of follicular (germinal) centers.
Infantile-onset multisystem autoimmune disease-1 is characterized by early childhood onset of a spectrum of autoimmune disorders affecting multiple organs. Common manifestations include insulin-dependent diabetes mellitus and autoimmune enteropathy, or celiac disease, and autoimmune hematologic disorders. Other features include short stature and nonspecific dermatitis. More variable features include hypothyroidism, autoimmune arthritis, and delayed puberty. Some patients may show recurrent infections. The disorder results from an inborn error of cytokine signaling (summary by Flanagan et al., 2014 and Milner et al., 2015). Genetic Heterogeneity of Infantile-Onset Multisystem Autoimmune Disease See also ADMIO2 (617006), caused by mutation in the ZAP70 gene (176947) on chromosome 2q12.
ACTH-independent macronodular adrenal hyperplasia-2 is an autosomal dominant tumor susceptibility with syndromic incomplete penetrance, as a second hit to the ARMC5 gene is required to develop macronodular hyperplasia (Assie et al., 2013).
Centronuclear myopathy-5 is an autosomal recessive congenital myopathy characterized by severe neonatal hypotonia with respiratory insufficiency and difficulty feeding. Some patients die in infancy, and some develop dilated cardiomyopathy. Children show severely delayed motor development (summary by Agrawal et al., 2014). For a discussion of genetic heterogeneity of centronuclear myopathy, see CNM1 (160150).
Poretti-Boltshauser syndrome is an autosomal recessive disorder characterized by cerebellar dysplasia, cerebellar vermis hypoplasia, cerebellar cysts in most patients, high myopia, variable retinal dystrophy, and eye movement abnormalities. Affected individuals have delayed motor development and often have speech delay. Cognitive function can range from normal to intellectually disabled (summary by Aldinger et al., 2014).
Nanophthalmos is characterized by axial lengths of the ocular globe that are more than 2 SDs smaller than the normal range, or less than 20 mm in adults, with a cornea and lens that are typically of normal size, associated with severe hyperopia (farsightedness) of +7.00 diopters or more. The smaller dimensions of the anterior chamber depth cause the iridocorneal angle to be typically narrow. Abnormal thickening of the scleral connective tissue is often observed (summary by Awadalla et al., 2014). For a discussion of genetic heterogeneity of nanophthalmos, see NNO1 (600165).
Immunodeficiency-27B results from autosomal dominant (AD) IFNGR1 deficiency. Patients with AD IFNGR1 deficiency commonly present with recurrent, moderately severe infections with environmental mycobacteria or bacillus Calmette-Guerin (BCG). In contrast with patients with complete autosomal recessive (AR) IFNGR1 deficiency (IMD27A), cells from patients with AD IFNGR1 deficiency display residual responses to IFNG in vitro, indicating that the deficiency in IFNGR1 is partial. The clinical features of AD IFNGR1 deficiency are usually less severe than those in children with complete AR IFNGR1 deficiency, and mycobacterial infection often occurs later (mean age of 13.4 years vs 1.3 years), with patients having longer mean disease-free survival. In patients with AD IFNGR1 deficiency, M. avium tends to cause unifocal or multifocal osteomyelitis. Salmonellosis is present in about 5% of patients with AR or AD IFNGR1 deficiency, and other infections have been reported in single patients (review by Al-Muhsen and Casanova, 2008).
Familial partial lipodystrophy-6 (FPLD6) is characterized by abnormal subcutaneous fat distribution, with variable excess accumulation of fat in the face, neck, shoulders, axillae, back, abdomen, and pubic region, and reduction in subcutaneous fat of the lower extremities. Progressive adult-onset myopathy is seen in some patients, and there is variable association with diabetes, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and hepatic steatosis (Zolotov et al., 2017).
Congnital aplastic deformities of the breast include amastia (total absence of breasts and nipple), athelia (absence of the nipple), and amazia (absence of the mammary gland). Most common is amastia. Bilateral absence of the breasts may occur as an isolated anomaly or may be associated with a syndrome or a cluster of other anomalies, including anhidrotic ectodermal dysplasia (305100) or Poland syndrome (173800) (summary by Papadimitriou et al., 2009). For a discussion of genetic heterogeneity of aplasia or hypoplasia of the breasts and/or nipples, see 113700.
Focal segmental glomerulosclerosis is a form of kidney injury defined by partial sclerosis of some but not all glomeruli. It is characterized clinically by significant proteinuria with or without features of nephrotic syndrome. Some patients develop end-stage renal disease (summary by Barua et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
IMD36 is a primary immunodeficiency with a highly heterogeneous clinical phenotype, characterized primarily by recurrent respiratory tract infections, lymphoproliferation, and antibody deficiency. Other features include growth retardation, mild neurodevelopmental delay, and autoimmunity. The major complication is development of B-cell lymphoma (Elkaim et al., 2016).
Hennekam lymphangiectasia-lymphedema syndrome is an autosomal recessive disorder characterized by generalized lymphatic dysplasia affecting various organs, including the intestinal tract, pericardium, and limbs. Additional features of the disorder include facial dysmorphism and cognitive impairment (summary by Alders et al., 2014). For a discussion of genetic heterogeneity of Hennekam lymphangiectasia-lymphedema syndrome, see HKLLS1 (235510).
GPIBD11 is an autosomal recessive disorder characterized by neonatal hypotonia, lack of psychomotor development, and variable seizures. Some patients may have dysmorphic features or increased serum alkaline phosphatase. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis (summary by Hogrebe et al., 2016). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
A rare genetic ectodermal dysplasia syndrome characterised by short stature, nail dystrophy and/or nail loss, oral mucosa and/or tongue hyperpigmentation, dentition abnormalities (delayed teeth eruption, hypodontia, enamel hypoplasia), keratoderma on the margins of the palms and soles and focal hyperkeratosis on the dorsum of the hands and feet. Additionally, dysphagia with oesophageal strictures, sensorineural deafness, bronchial asthma and severe iron-deficiency anaemia have also been observed.
A decreased concentration of free (unbound) carnitine in the blood.
Neu-Laxova syndrome-2 is a rare autosomal recessive disorder characterized by a recognizable pattern of severe congenital malformations leading to prenatal or early postnatal lethality. Affected patients have abnormal craniofacial features, microcephaly, intrauterine growth retardation, ichthyosis, flexion deformities, limb malformations, and edema of the hands and feet. Some patients have malformations of the central nervous system, such as abnormal gyration (summary by Acuna-Hidalgo et al., 2014). For a discussion of genetic heterogeneity of Neu-Laxova syndrome, see NLS1 (256520).
Vestibular areflexia can be measured as the absence of the caloric nystagmus response in electronystagmography. [HPO:probinson]
Autoinflammation with infantile enterocolitis is an autosomal dominant disorder characterized by onset of recurrent flares of autoinflammation in early infancy. Affected individuals tend to have poor overall growth and gastrointestinal symptoms in infancy associated with laboratory evidence of activated inflammation. This initial presentation is followed by recurrent febrile episodes with splenomegaly and sometimes hematologic disturbances, arthralgias, or myalgias. The disorder results from overactivation of an arm of the immune response system (Romberg et al., 2014; Canna et al., 2014).
A reduction in the degree of glycosylation of alpha-dystroglycan in muscle tissue.
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shape, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), the existence of several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, suggest that the distinctions among these variants may be artificial. Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis. It is characterized by multiple small, annular, anhidrotic, keratotic lesions that are located predominantly on sun-exposed areas of the skin, such as the face, neck, and distal limbs. The lesions typically begin to develop in adolescence and reach near-complete penetrance by the third or fourth decade of life (summary by Wu et al., 2004 and Zhang et al., 2012). For a discussion of genetic heterogeneity of porokeratosis, see 175800.
An increased susceptibility to bronchiolitis as manifested by a history of recurrent bronchiolitis.
Pontocerebellar hypoplasia type 1C is a severe autosomal recessive neurodegenerative disorder characterized by severe muscle weakness and failure to thrive apparent in the first months of life. Affected infants showed delayed psychomotor development, often with visual and hearing impairment, and may die of respiratory failure. Brain imaging typically shows cerebellar hypoplasia, hypoplasia of the corpus callosum, and immature myelination (summary by Boczonadi et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (607596).
Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) is an autosomal recessive syndromic disorder characterized by onset of severe sideroblastic anemia in the neonatal period or infancy. Affected individuals show delayed psychomotor development with variable neurodegeneration. Recurrent periodic fevers without an infectious etiology occur throughout infancy and childhood; immunologic work-up shows B-cell lymphopenia and hypogammaglobulinemia. Other more variable features include sensorineural hearing loss, retinitis pigmentosa, nephrocalcinosis, and cardiomyopathy. Death in the first decade may occur (summary by Wiseman et al., 2013).
Autoimmune lymphoproliferative syndrome type V is an autosomal dominant complex immune disorder characterized by autoimmune thrombocytopenias and abnormal lymphocytic infiltration of nonlymphoid organs, including the lungs, brain, and gastrointestinal tract, resulting in enteropathy. Some patients may show features of an immunodeficiency syndrome with recurrent infections, but immunosuppressive therapy often results in clinical improvement (summary by Kuehn et al., 2014). For a general description and a discussion of genetic heterogeneity of ALPS, see 601859.
Generalized pustular psoriasis (GPP) is a severe form of a skin disorder called psoriasis. GPP and other forms of psoriasis are caused by abnormal inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, when inflammation is abnormal and uncontrolled, it can damage the body's tissues and organs. Individuals with GPP have repeated episodes in which large areas of skin become red and inflamed and develop small pus-filled blisters (pustules). The skin problems can be accompanied by fever, extreme tiredness (fatigue), muscle weakness, an increased number of white blood cells, and other signs of inflammation throughout the body (systemic inflammation). The inflammation problems subside and reappear often. Episodes can be triggered by infection, exposure to or withdrawal from certain medications, menstruation, or pregnancy, although the trigger is often unknown. GPP can be life-threatening if not treated.While many affected individuals have features only of GPP (called GPP alone), some develop features of another skin condition called psoriasis vulgaris (PV), either before or after GPP appears. PV, the most common form of psoriasis, is characterized by red, scaly patches of skin (plaques) on parts of the body.
IMD38 predisposes individuals to severe clinical disease upon infection with weakly virulent mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines (Bogunovic et al., 2012). Patients do not experience severe disease in response to viral infection. Affected individuals have intracranial calcification (Zhang et al., 2015).
Autosomal recessive spinocerebellar ataxia-17 is a neurologic disorder characterized by onset of gait ataxia and cerebellar signs in early childhood. Patients also have variable intellectual disability (summary by Evers et al., 2016).
Hypomyelinating leukodystrophy-9 is an autosomal recessive neurologic disorder characterized by onset of delayed psychomotor development, spasticity, and nystagmus in the first year of life. Additional neurologic features such as ataxia and abnormal movements may also occur. Brain imaging shows diffuse hypomyelination affecting all regions of the brain (summary by Wolf et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080.
Macular dystrophies are inherited retinal dystrophies in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea, the cone-rich region of the central retina. Vitelliform macular dystrophies (VMDs) form a subset of macular dystrophies characterized by round yellow deposits, usually at the center of the macula and containing lipofuscin, a chemically heterogeneous pigment visualized by autofluorescence imaging of the fundus (summary by Manes et al., 2013). Vitelliform macular dystrophy-4 is characterized by late-onset moderate visual impairment, small satellite drusen-like lesions in the foveal area, preservation of retinal pigment epithelium (RPE) reflectivity, deposits above the RPE between the ellipsoid and outer segment interdigitation lines on spectral-domain optical coherence tomography (SD-OCT), and normal or borderline results on electrooculography (EOG) (Meunier et al., 2014). For a discussion of genetic heterogeneity of vitelliform macular dystrophy, see VMD1 (153840).
Macular dystrophies are inherited retinal dystrophies in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea, the cone-rich region of the central retina. Vitelliform macular dystrophies (VMDs) form a subset of macular dystrophies characterized by round yellow deposits, usually at the center of the macula and containing lipofuscin, a chemically heterogeneous pigment visualized by autofluorescence imaging of the fundus (summary by Manes et al., 2013). Vitelliform macular dystrophy-5 is characterized by late-onset moderate visual impairment, preservation of retinal pigment epithelium (RPE) reflectivity, deposits above the RPE between the ellipsoid and outer segment interdigitation lines on spectral-domain optical coherence tomography (SD-OCT), and normal or borderline results on electrooculopathy (EOG) (Meunier et al., 2014). For a discussion of genetic heterogeneity of vitelliform macular dystrophy, see VMD1 (153840).
Peroxisomal fatty acyl-CoA reductase-1 disorder is an autosomal recessive disorder characterized by onset in infancy of severely delayed psychomotor development, growth retardation with microcephaly, and seizures. Some patients may have congenital cataracts and develop spasticity later in childhood. Biochemical studies tend to show decreased plasmalogen, consistent with a peroxisomal defect. The disorder is reminiscent of rhizomelic chondrodysplasia punctata (see, e.g., RCDP1, 215100), although the characteristic skeletal abnormalities observed in RCDP are absent (Buchert et al., 2014).
Charcot-Marie-Tooth disease type 2S is a relatively pure form of autosomal recessive axonal neuropathy characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy affecting the lower and upper limbs. Patients have decreased reflexes and variable distal sensory impairment (summary by Cottenie et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
PURA-related neurodevelopmental disorders include PURA syndrome, caused by a heterozygous pathogenic sequence variant in PURA, and 5q31.3 deletion syndrome, caused by a genomic 5q31.3 deletion encompassing all or part of PURA.PURA-related neurodevelopmental disorders are characterized by moderate to severe neurodevelopmental delay with absence of speech in most and lack of independent ambulation in many. Early-onset problems can include hypotonia, hypothermia, hypersomnolence, feeding difficulties, excessive hiccups, recurrent central and obstructive apneas, epileptic seizures, abnormal nonepileptic movements (dystonia, dyskinesia, and dysconjugate eye movements), and abnormal vision. Congenital heart defects, urogenital malformations, skeletal abnormalities, and endocrine disorders occur, but are less common.
Microcephaly and chorioretinopathy-2 is an autosomal recessive developmental disorder characterized by delayed psychomotor development, visual impairment, and short stature (summary by Martin et al., 2014). For a discussion of genetic heterogeneity of microcephaly and chorioretinopathy, see MCCRP1 (251270).
Generalized epilepsy with febrile seizures plus-9 is an autosomal dominant neurologic disorder characterized by onset of febrile and/or afebrile seizures in early childhood, usually before age 3 years. Seizure types are variable and include generalized tonic-clonic, atonic, myoclonic, complex partial, and absence. Most patients have remission of seizures later in childhood with no residual neurologic deficits, but rare patients may show mild developmental delay or mild intellectual disabilities (summary by Schubert et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of GEFS+, see 604233.
Progressive myoclonic epilepsy-7 is a neurologic disorder characterized by onset of severe progressive myoclonus and infrequent tonic-clonic seizures in the first or second decades of life. Most patients become wheelchair-bound; some patients may have cognitive decline (summary by Muona et al., 2015). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
Combined oxidative phosphorylation deficiency-23 is an autosomal recessive disorder characterized by early childhood onset of hypertrophic cardiomyopathy and/or neurologic symptoms, including hypotonia and delayed psychomotor development. Laboratory investigations are consistent with a defect in mitochondrial function resulting in lactic acidosis, impaired activities of respiratory complexes I and IV, and defective translation of mitochondrial proteins. Brain imaging shows abnormal lesions in the basal ganglia, thalamus, and brainstem. The severity of the disorder is variable, ranging from death in early infancy to survival into the second decade (summary by Kopajtich et al., 2014). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Polyglucosan body myopathy-2 is an autosomal recessive disorder characterized by proximal muscle weakness of the lower limbs resulting in gait disturbances. Some patients also have involvement of the upper limbs and/or distal muscle weakness. The age at onset is highly variable, and the disorder is slowly progressive. Muscle biopsy shows accumulation of polyglucosan, which contains abnormally long and poorly branched glucosyl chains and is variably resistant to digestion by alpha-amylase (summary by Malfatti et al., 2014). For a discussion of genetic heterogeneity of PGBM, see PGBM1 (615895).
Ruijs et al. (2003) reported a Moroccan boy with a chromosomal breakage who died of hepatocellular carcinoma at age 17 years. The boy was noted to have growth retardation at age 3 years; at age 7 he was found to have thoracic kyphosis, frontal bossing, and a delayed bone age of approximately 3 years. He underwent surgery for severe bilateral posterior subcapsular cataracts at age 14. Examination at age 15 showed short stature and low weight, with premature graying of scalp hair, small frontotemporal diameter, small deep-set eyes, bulbous nose with high nasal bridge, small upper lip, and micrognathia. In addition, he had thoracic kyphoscoliosis, sloping shoulders, mild pectus excavatum, moderate bilateral contractures of both elbows, bilateral clinodactyly, and pes planus. At age 17, he developed abdominal pain, and ultrasonography revealed a liver mass; biopsy confirmed hepatocellular carcinoma. Because of the advanced stage, no treatment was possible, and he died 2 months later. Although his parents were not known to be consanguineous, they originated from the same small Moroccan village. Lessel et al. (2014) studied 2 brothers from a nonconsanguineous Australian family of European ancestry who exhibited low body weight, micrognathia, triangular face, muscular atrophy, lipodystrophy, bilateral simian creases, delayed bone age, and mild joint restrictions in the fingers and elbows. In addition, both brothers developed early-onset hepatocellular carcinoma, at ages 16 and 14 years, respectively. The older brother died at age 18 from complications of acute fulminant hepatic failure. Analysis of patient tumor biopsies showed strong focal accumulations of cancer biomarkers as well as a high proliferative index compared to healthy liver or to cells from idiopathic hepatocellular carcinoma.
Chronic atrial and intestinal dysrhythmia (CAID) is a disorder affecting the heart and the digestive system. CAID disrupts the normal rhythm of the heartbeat; affected individuals have a heart rhythm abnormality called sick sinus syndrome. The disorder also impairs the rhythmic muscle contractions that propel food through the intestines (peristalsis), causing a digestive condition called intestinal pseudo-obstruction. The heart and digestive issues develop at the same time, usually by age 20.Sick sinus syndrome (also known as sinus node dysfunction) is an abnormality of the sinoatrial (SA) node, which is an area of specialized cells in the heart that functions as a natural pacemaker. The SA node generates electrical impulses that start each heartbeat. These signals travel from the SA node to the rest of the heart, signaling the heart (cardiac) muscle to contract and pump blood. In people with sick sinus syndrome, the SA node does not function normally, which usually causes the heartbeat to be too slow (bradycardia), although occasionally the heartbeat is too fast (tachycardia) or rapidly switches from being too fast to being too slow (tachycardia-bradycardia syndrome). Symptoms related to abnormal heartbeats can include dizziness, light-headedness, fainting (syncope), a sensation of fluttering or pounding in the chest (palpitations), and confusion or memory problems. During exercise, many affected individuals experience chest pain, difficulty breathing, or excessive tiredness (fatigue).In intestinal pseudo-obstruction, impairment of peristalsis leads to a buildup of partially digested food in the intestines, abdominal swelling (distention) and pain, nausea, vomiting, and constipation or diarrhea. Affected individuals experience loss of appetite and impaired ability to absorb nutrients, which may lead to malnutrition. These symptoms resemble those caused by an intestinal blockage (obstruction) such as a tumor, but in intestinal pseudo-obstruction no such blockage is found.
Cerebellofaciodental syndrome is an autosomal recessive neurodevelopmental disorder characterized by delayed development, intellectual disability, abnormal facial and dental findings, and cerebellar hypoplasia (summary by Borck et al., 2015).
Autosomal recessive spinocerebellar ataxia-18 is a neurologic disorder characterized by delayed psychomotor development, severely impaired gait due to cerebellar ataxia, ocular movement abnormalities, and intellectual disability. Brain imaging shows progressive cerebellar atrophy (summary by Hills et al., 2013).
Lissencephaly-6 is an autosomal recessive neurodevelopmental disorder characterized by severe microcephaly and developmental delay. Brain imaging shows variable malformations of cortical development, including lissencephaly, pachygyria, and hypoplasia of the corpus callosum (summary by Mishra-Gorur et al., 2014). For a general description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Thrombocytopenia-5 is an autosomal dominant disorder characterized by a decreased number of platelets and a bleeding tendency. Affected individuals have an increased susceptibility to the development of hematologic malignancies, and possibly to solid neoplasms. Thrombocytopenia is usually apparent in early childhood, whereas the development of malignancy can occur throughout life (summary by Zhang et al., 2015). For a discussion of genetic heterogeneity of thrombocytopenia, see 313900.
Amelogenesis imperfecta type IH is characterized by hypoplastic and hypomineralized tooth enamel that may be rough, pitted, and/or discolored (Wang et al., 2014 and Poulter et al., 2014).
Temple syndrome is a short stature disorder of imprinting. The cardinal features are low birth weight, hypotonia and motor delay, feeding problems early in life, early puberty, and significantly reduced final height. Facial features include a broad forehead and short nose with a wide nasal tip, and the majority of patients have small hands and feet. However, many of the clinical features are nonspecific, making diagnosis difficult. In addition, isodisomy may uncover recessive disorders, which may influence the phenotype in maternal uniparental disomy of chromosome 14 (UPD14mat) cases (summary by Ioannides et al., 2014).
Osteogenesis imperfecta type XVI (OI16) is characterized by prenatal onset of multiple fractures of ribs and long bones, blue sclerae, decreased ossification of the skull, and severe demineralization. Heterozygous family members may exhibit recurrent fractures with minimal trauma, osteopenia, and blue sclerae (Keller et al., 2018; Lindahl et al., 2018).
Vacuolar myopathy with CASQ1 aggregates is an autosomal dominant mild muscle disorder characterized by adult onset of muscle cramping and weakness as well as increased levels of serum creatine kinase (CK). The disorder is not progressive, and some patients may be asymptomatic (summary by Rossi et al., 2014).
Charcot-Marie-Tooth disease type 2T (CMT2T) is a slowly progressive autosomal recessive sensorimotor peripheral neuropathy with onset in middle age (Higuchi et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Combined oxidative phosphorylation deficiency-24 is an autosomal recessive mitochondrial disorder with wide phenotypic variability. Some patients have a milder form affecting only skeletal muscle, whereas others may have a more severe infantile-onset neurodegenerative disorder (Vanlander et al., 2015; Sofou et al., 2015). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Tenorio syndrome is characterized by overgrowth, macrocephaly, and intellectual disability (ID). Some patients may have mild hydrocephaly, hypoglycemia, and inflammatory diseases resembling Sjogren syndrome (270150) (summary by Tenorio et al., 2014).
Peeling skin syndrome-3 is characterized by asymptomatic lifelong and continuous shedding of the stratum corneum of the epidermis. Symptoms start during the second half of the first decade of life and consist of generalized white scaling occurring over the upper and lower extremities (Cabral et al. (2012)). For a discussion of genetic heterogeneity of peeling skin syndrome, see PSS1 (270300).
Decreased or absent activity of the enzyme carbonic anhydrase 1, due to loss-of-function mutation(s) in the gene CA1.
A very rare genetic syndrome characterized by reduced replicative DNA ligase I. It results in immunodeficiency and cellular hypersensitivity to DNA-damaging agents.
A rare severe and life-threatening genetic disease occurring during the neonatal period. The disease has characteristics of classical Marfan syndrome manifestations in addition to facial dysmorphism (megalocornea, iridodonesis, ectopia lentis, crumpled ears, loose redundant skin giving a 'senile' facial appearance), flexion joint contractures, pulmonary emphysema and a severe, rapidly progressive cardiovascular disease (including ascending aortic dilatation and severe mitral and/or tricuspid valve insufficiency). Additionally, skeletal manifestations (arachnodactyly, dolichostenomelia, pectus deformities) are also associated.
Central core disease is a disorder that affects muscles used for movement (skeletal muscles). This condition causes muscle weakness that ranges from almost unnoticeable to very severe.Most people with central core disease experience persistent, mild muscle weakness that does not worsen with time. This weakness affects the muscles near the center of the body (proximal muscles), particularly muscles in the upper legs and hips. Muscle weakness causes affected infants to appear ""floppy"" and can delay the development of motor skills such as sitting, standing, and walking. In severe cases, affected infants experience profoundly weak muscle tone (hypotonia) and serious or life-threatening breathing problems. Central core disease is also associated with skeletal abnormalities such as abnormal curvature of the spine (scoliosis), hip dislocation, and joint deformities called contractures that restrict the movement of certain joints.Many people with central core disease also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.Central core disease gets its name from disorganized areas called cores, which are found in the center of muscle fibers in many affected individuals. These abnormal regions can only be seen under a microscope. Although the presence of cores can help doctors diagnose central core disease, it is unclear how they are related to muscle weakness and the other features of this condition.
Syndrome with the association of gastrointestinal dysmotility, peripheral neuropathy, chronic progressive external ophthalmoplegia and leukoencephalopathy. The symptoms are progressive and the clinical picture is dominated by severe gastrointestinal disorders due to abnormal bowel motility. Morphological studies of the muscles reveal the presence of a low proportion of muscle fibers with mitochondrial proliferation (ragged-red fibers) or cytochrome c oxidase deficiency. Inherited in an autosomal recessive manner and is caused by mutations in the TYMP gene (22q13.32-qter).
Immunodeficiency-32B is an autosomal recessive primary immunodeficiency characterized by recurrent infections resulting from variable defects in immune cell development or function, including monocytes, dendritic cells, and natural killer (NK) cells. Patients have particular susceptibility to viral disease (summary by Mace et al., 2017).
Imerslund-Gräsbeck syndrome is a condition caused by low levels of vitamin B12 (also known as cobalamin). The primary feature of this condition is a blood disorder called megaloblastic anemia. In this form of anemia, which is a disorder characterized by the shortage of red blood cells, the red cells that are present are abnormally large. About half of people with Imerslund-Gräsbeck syndrome also have high levels of protein in their urine (proteinuria). Although proteinuria can be an indication of kidney problems, people with Imerslund-Gräsbeck syndrome appear to have normal kidney function.Imerslund-Gräsbeck syndrome typically begins in infancy or early childhood. The blood abnormality leads to many of the signs and symptoms of the condition, including an inability to grow and gain weight at the expected rate (failure to thrive), pale skin (pallor), excessive tiredness (fatigue), and recurring gastrointestinal or respiratory infections. Other features of Imerslund-Gräsbeck syndrome include mild neurological problems, such as weak muscle tone (hypotonia), numbness or tingling in the hands or feet, movement problems, delayed development, or confusion. Rarely, affected individuals have abnormalities of organs or tissues that make up the urinary tract, such as the bladder or the tubes that carry fluid from the kidneys to the bladder (the ureters).
Opacification and vascularisation of the cornea, often associated with macula hypoplasia. The prevalence is unknown. The syndrome is transmitted in an autosomal dominant manner and is associated with mutations in the PAX6 gene. The presence of macular hypoplasia and iris anomalies in some familial cases suggest that in these cases the disease may be a form of aniridia.
Trichothiodystrophy is a rare autosomal recessive disorder in which patients have brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern, called 'tiger tail banding,' under polarizing microscopy. TTD patients display a wide variety of clinical features, including cutaneous, neurologic, and growth abnormalities. Common additional clinical features are ichthyosis, intellectual/developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections. There are both photosensitive and nonphotosensitive forms of the disorder. Patients with TTD have not been reported to have a predisposition to cancer (summary by Faghri et al., 2008). For a discussion of genetic heterogeneity of TTD, see 601675.
The sulfate ester form of isavuconazonium, a prodrug of the triazole antifungal agent isavuconazole, with broad-spectrum antifungal activity. Upon administration, isavuconazonium sulfate is hydrolyzed by plasma esterases to yield the active moiety isavuconazole. Isavuconazole binds to and inhibits the fungal cytochrome P450 family enzyme lanosterol 14-alpha-demethylase (CYP51), which catalyzes the demethylation of lanosterol to yield ergosterol, an important component of the fungal cell membrane. Inhibition of CYP51 leads to a decrease in fungal ergosterol production and disrupts synthesis of the fungal cell membrane, which decreases membrane integrity, increases cell membrane permeability and promotes the loss of essential intracellular elements. This results in fungal cell lysis and death.
An abnormality of fear/anxiety-related behavior, which may relate to either abnormally reduced fear/anxiety-related response or increased fear/anxiety-related response.
The J wave is a positive convex deflection that occurs at the junction of the QRS complex and ST segment, the J-point.
A type of pituitary adenoma that produces grwoth hormone.
An abnormality of the respiratory system, which include the airways, lungs, and the respiratory muscles.
At a point before the usual, expected, or specified time.
Tumors or cancer found specifically in one human BREAST, but not in both.
The presence of an abnormally large pelvis.
Substances that bind to and inhibit the action of OREXIN RECEPTORS. Drugs in this class have been used as SLEEP AIDS.
The presence of developmental dysplasia of the pancreas.
The pregnancy status of an individual at the time of an illness or condition.
Persistent difficulty with speech sound production such that it interferes with verbal communication.
The presence of circulating autoantibodies to phospholipids.
Substances that facilitate the cessation of tobacco smoking.
Increased width of the proximal phalanx of the 4th finger.
An abnormality of the conduction of electrical impulses by peripheral (motor or sensory) nerves. This finding is elicited by a nerve conduction study (NCS).
Median longitudinal length of the ear more than two standard deviations below the mean in the presence of some, but not all, parts of the normal ear.
Reduced or inadequate peristalsis, with resultant slow passage of contents through the digestive tract.
The presence of a neoplasm of the testis with origin in a Sertoli cell.
A condition characterized by dilatation of the Bowman space and affecting more than 5% of the glomeruli.
The nostrils (the paired channels of the nose) are not present.
A tumor (abnormal growth of tissue) of the biliary system.
A small, skin-lined tract that leads from the surface to deep within the tissues.
An abnormal functionality of the male genital system.
Increased dimensions of the Virchow-Robin spaces (also known as perivascular spaces), which surround the walls of vessels as they course from the subarachnoid space through the brain parenchyma. Perivascular spaces are commonly microscopic, and not visible on conventional neuroimaging. This term refers to an increase of size of these spaces such that they are visible on neuroimaging (usually magnetic resonance imaging). The dilatations are regular cavities that always contain a patent artery.
Underdeveloped posterior communicating artery.
An ophthalmologic sign in young children resulting from upward-gaze paresis. In this condition, the eyes appear driven downward, the sclera may be seen between the upper eyelid and the iris, and part of the lower pupil may be covered by the lower eyelid.
A chronic loss of wrist joint motion on one side only.
Coronary disease that has not progressed to the point of causing significant occlusion (blockage) of the coronary arteries.
An abnormality of actions or reactions of a person taking place during interactions with others.
An abnormal increase in intracellular lipid droplets In a muscle. The number and size of these drops can increase with somd disorders of lipid metabolism affecting muscle. See pmid 20691590 for histological images.
An anomaly of the concentration or homeostasis of creatine. Creatine is a derivative of glycine having methyl and amidino groups attached to the nitrogen. Creatine is naturally produced from amino acids, primarily in liver and kidney, and acts as an energy source for cells, primarly for muscle cells.
Rhythmic, involuntary sinusoidal oscillations of one or both eyes. The waveform of pendular nystagmus may occur in any direction.
An increased concentration of vanillylmandelic acid in the urine.
An increased concentration of homovanillic acid in the urine.
A reduction in the activity of the mitochondrial proton-transporting ATP synthase complex, which makes ATP via oxidative phosphorylation, and is sometimes described as Complex V of the electron transport chain.
A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria.
Bending or curvature of a fourth toe in the tibial direction (i.e., towards the big toe).
Hypercortisolemia associated with a overproduction of ACTH (often from a tumor), leading secondarily to overproduction of cortisol.
A form of primary hyperaldosteronism in which the overproduction of aldosterone cannot be suppressed by the administration of dexamethasone or similar glucocorticoids.
Adrenal insufficiency secondary to a defect in the corticotropin-releasing hormone receptor.
The enteric villi are atrophic or absent.
Microcephaly (HP:0000252) that is present already at the time of birth.
Underdevelopment of the vestibular nerve.
Formation of excess fibrous connective tissue in the tunica intima (innermost layer) of arteries.
Bilateral temporal scarlike defects, which are said to resemble forceps marks.
Synostosis affecting only one of the coronal sutures.
An abnormal level of a circulating protein in the blood.
A developmental defect characterized by fusion of the left and right halves of the thalamus.
An abnormality of the premaxilla (the embryonic structure that forms the anterior part of the maxilla) causing it to appear relatively small in size compared to the other parts of the maxilla or other facial structures.
Distance between the labial point of the incisive papilla to the midline junction of the hard and soft palate more than 2 SD below the mean (objective) or apparently decreased length of the hard palate (subjective).
Short second metacarpal bone because of developmental hypoplasia.
Sclerosis of the epiphysis of the proximal phalanx of the little finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
A cone-shaped appearance of the epiphysis of the proximal phalanx of the little finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
An abnormality of the axial skeleton, which comprises the skull, the vertebral column, the ribs and the sternum.
A mild form of hypospadias in which the urethra opens just under the corona glandis.
Aplasia or developmental hypoplasia of the fallopian tube.
Median longitudinal length of the ear more than two standard deviations below the mean in the presence of some, but not all, parts of the normal ear. [eom:ae27d9699faef13a, pmid:19152421]
The presence of a moderate form of sensorineural hearing impairment.
A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria.
A reduction in the activity of the mitochondrial respiratory chain complex II, which is part of the electron transport chain in mitochondria.
Abnormal morphology of collagen fibers in cartilage. In cartilage, collagen II, actually a collagen II:IX:XI heterofibril, is by far the most important type of collagen. A number of abnormalities may be appreciated by electron micrography or biochemical investigations, including sparse collagen fibers in the cartilage matrix.
The congenital absence of the thyroid gland.
An abnormal conical morphology of the primary or permanent mandibular incisors.
At birth, newborns are endowed with maternal antibodies. IgG production normally begins at the age of two months. A delay in recovery from this physiological hypogammaglobulinemia between the 3rd and the 6th month of life, and of recovery period between 18 and 36 months defines transient newborn hypogammaglobulinemia.
Persistent overgrowth of Candida albicans in the gastrointestinal tract.
Irregular surface of the normally relatively smooth capital femoral epiphysis.
An abnormality of magnesium ion homeostasis.
Increased bone density affecting the bones of the spine (vertebral column).
An abnormality of alkaline phosphatase activity.
An abnormality of fatty acid metabolism.
An abnormal union between bones or parts of bones of the hand.
Osteolytic defects of the phalanges of the 4th (ring) finger.
Ossification of hand bones is less advanced than would be expected according to age-adjusted norms.
Ossification of hand bones at an earlier age than normal.
Ossification of the humeral epiphysis at an earlier age than normal.
Spontaneous, repetitive electrical activity demonstrated by electromyography (EMG).
A compound muscle action potential (CMAP) is a type of electromyography (EMG). CMAP refers to a group of almost simultaneous action potentials from several muscle fibers in the same area evoked by stimulation of the supplying motor nerve and are recorded as one multipeaked summated action potential. This abnormality refers to a greater than normal decrease in the amplitude during the course of the investigation.
Any abnormality of the neuromuscular junction, which is the synapse between the motor end plate of a motor neuron and the skeletal muscle fibers.
When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval.
An abnormal decrease in orotidine 5'-phosphate decarboxylase activity.
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
Abnormality of the corticospinal tract, which is the chief element of the pyramidal system (the principle motor tract) and is the only direct connection between the cerebrum and the spinal cord.
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger).
Lipofuscin, a generic term applied to autofluorescent lipopigment, is a mixture of protein and lipid that accumulates in most aging cells, particularly those involved in high lipid turnover (e.g., the adrenal medulla) or phagocytosis of other cell types (e g., the retinal pigment epithelium or RPE; macrophage). This term pertains if there is an increase in the neuronal accumulation of lipofuscin (also known as autofluorescent lipoprotein) more than expected for the age of the patient.
An anomaly of erythroid lineage cells, that is, of the erythropoietic cells in the lineage leading to and including erythrocytes.
A structural abnormality of the abdomen ('belly'), that is, the part of the body between the pelvis and the thorax.
Structural abnormality affecting one or more of the cranial nerves, which emerge directly from the brain stem.
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Redness of the skin of the face, caused by hyperemia of the capillaries in the lower layers of the skin.
The presence of any abnormality of the genitourinary system.
Increased side-to-side width of the xiphoid process of the sternum.
A deviation from normal of the concentration of 2-oxoglutaric acid in the urine.
Partial or complete duplication of one or more phalanx of little toe.
The presence of multiple sausage-shaped swellings of the myelin sheath (The Latin tomaculum means sausage).
Dissolution or degeneration of bone tissue of one or more phalanges of the thumb.
Failure to form (agenesis) of one or more epiphyses of the big toe.
The presence of spots or rounded patches of abnormally increased density of metaphyseal bone.
A darker than expected signal on magnetic resonance imaging emanating from the cerebral white matter.
Insertion of the posterior columella superior to the nasal base.
Increased protrusion of the antihelical ridge, proximal to its bifurcation, relative to the prominence of the helix.
The presence of one or more dendritic corneal epithelial ulcers characterized by a treelike branching linear pattern with feathery edges and terminal bulbs. Herpetiform corneal ulcers can be identified by fluorescein staining.
Flaring (increase of width with a splayed appearance) of the humeral metaphysis.
Folds or ridges within the concha that are distinct from the crus helix.
Vertical crease fold situated below the vermilion border of the lower lip and above the fatty pad of the chin with the face at rest.
Different levels of maturation of different bones.
Dense radiopaque bands of bone which are thicker than the adjacent diaphyseal cortex and may form at the metaphysis of growing bones. They appear on radiographs as bone that is more radiopaque that the adjacent diaphyseal cortex.
An increase in size of the subarachnoid space associated with the lateral cerebral sulcus (Sylvian fissure).
An elevation in bone density in one or more distal phalanges of the toes. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more middle phalanges of the toes. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more proximal phalanges of the toes. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more phalanges of the big toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more phalanges of the fifth toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more phalanges of the fourth toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more phalanges of the third toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more phalanges of the second toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more foot bones. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more phalanges of the toes. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more distal phalanges of the fifth finger. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more distal phalanges of the fourth finger. Sclerosis is normally detected on a radiograph as an area of increased opacity. [HPO:probinson]
An elevation in bone density in one or more distal phalanges of the third finger. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more distal phalanges of the second finger. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more proximal phalanges of the fingers. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more middle phalanges of the fingers. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more distal phalanges of the fingers. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in one or more phalanges of the fingers. Sclerosis is normally detected on a radiograph as an area of increased opacity.
Increased prominence of the xiphoid process of the sternum.
A cleft of the xiphoid process of the sternum.
An abnormality of the Common bile duct, a tube-like anatomic structure in the human gastrointestinal tract, formed by the union of the Common hepatic duct and the Cystic duct from the gall bladder.
Persistence of the embryonic dorsal or sciatic vein system that normally should have involuted around the tenth to twelfth week of intrauterine life.
An abnormality of the plantar part of foot, that is of the soles of the feet.
Telangiectases (small dilated blood vessels) located on the skin of sole of foot.
The presence of telangiectases on the skin of palm of hand.
A tumor (abnormal growth of tissue) of the male external genitalia.
An abnormality of the development of the fingernails.
An anomaly of one or more epiphyses of one or more vertebrae.
A horizontal cleft of the face, varying from slight widening of the mouth, to a cleft extending to the ear.
An increase in the degree of curvature of the cornea compared to normal.
Abnormal structure or form of trabecular bone.
An abnormality of the pigmentation of the mucosa of the mouth.
A displacement of the external urethral orifice from its normal position (in males normally placed at the tip of glans penis, in females normally placed about 2.5 cm behind the glans clitoridis and immediately in front of that of the vagina).
The nostrils (the paired channels of the nose) are not present. [HPO:probinson]
A fibrous cardiac diverticulum refers to an aneurysm and usually appears as an isolated congenital anomaly.
A cardiac diverticulum is a rare congenital malformation which is either fibrous or muscular.
An abnormality of the formation and mineralization of one or more vertebrae.
An abnormality of the forebrain, which has as its parts the telencephalon, diencephalon, lateral ventricles and third ventricle.
Inflammation of the eye, parts of the eye or the periorbital region.
Bony fusion of the middle and proximal phalanges of the 2nd toe.
Bony fusion of the middle and proximal phalanges of the 5th toe.
Bony fusion of the middle and proximal phalanges of the 4th toe.
Bony fusion of the middle and proximal phalanges of the 3rd toe.
Partial duplication of the proximal phalanx of fifth toe.
Partial duplication of proximal phalanx of third toe.
Partial duplication of the middle phalanx of the 5th toe.
Partial duplication of middle phalanx of fourth toe.
Partial duplication of middle phalanx of third toe.
Partial duplication of the distal phalanx of little toe.
Partial duplication of the distal phalanx of fourth toe.
Partial duplication of distal phalanx of third toe.
Complete duplication of the proximal phalanx of fifth toe.
Complete duplication of the middle phalanx of the 5th toe.
Complete duplication of middle phalanx of fourth toe.
Complete duplication of middle phalanx of third toe.
Complete duplication of the distal phalanx of little toe.
Complete duplication of the distal phalanx of fourth toe.
Complete duplication of distal phalanx of third toe.
Partial or complete duplication of the proximal phalanx of fifth toe.
Partial or complete duplication of the proximal phalanx of fourth toe.
Partial or complete duplication of proximal phalanx of third toe.
Partial or complete duplication of the middle phalanx of the 5th toe.
Partial or complete duplication of middle phalanx of fourth toe.
Partial or complete duplication of middle phalanx of third toe.
Partial or complete duplication of the distal phalanx of little toe.
Partial or complete duplication of the distal phalanx of fourth toe.
Partial or complete duplication of distal phalanx of third toe.
Developmental hypoplasia of the proximal phalanx of fifth toe.
Developmental hypoplasia of the proximal phalanx of fourth toe.
Abnormal reduction in length of proximal phalanx of third toe.
Developmental hypoplasia of the middle phalanx of the 5th toe.
Developmental hypoplasia of the middle phalanx of fourth toe.
Developmental hypoplasia of the middle phalanx of third toe.
Developmental hypoplasia of the distal phalanx of little toe.
Developmental hypoplasia of the distal phalanx of fourth toe.
Developmental hypoplasia of the distal phalanx of third toe.
Absence of proximal phalanx of third toe, owing to a congenital defect of development.
Developmental aplasia of the middle phalanx of third toe.
Developmental aplasia of the distal phalanx of third toe.
Developmental hypoplasia of one or more phalanx of little toe.
Developmental hypoplasia of one or more phalanx of fourth toe.
Developmental hypoplasia of the phalanx of third toe.
The distal interphalangeal joint of the 2nd toe cannot be straightened actively or passively.
The proximal interphalangeal joint of the fifth toe cannot be straightened actively or passively.
The proximal interphalangeal joint of the 4th toe cannot be straightened actively or passively.
The proximal interphalangeal joint of the 3rd toe cannot be straightened actively or passively.
The proximal interphalangeal joint of the 2nd toe cannot be straightened actively or passively.
Clefting of the upper lip affecting the lateral portions of the upper lip rather than the midline/median region.
Cerebral eosinophilic, discrete, intracytoplasmatic inclusions of unknown significance.
Presence of abundant argyrophilic grains and coiled bodies on microscopic examination of brain tissue.
Unusual regions of densely packed membranous tubules known as tubular aggregates which present as membranous inclusions, derived from membranes of sarcoplasmic reticulum and mitochondria, containing miscellaneous proteins with a variety of enzymatic activities.
The carpus consists of the scaphoid, lunate, triquetal, pisiform, captitate, hamate, trapezoid, and trapezium bones. The tarsus consists of the talus, calcaneus, navicular, cuboid, cuneiform, and navicular bones. This term applies if there is any fusion among the bones of the carpus or tarsus.
An abnormality of the structure or form of the tendons, also often called sinews.
An abnormality of the medullary cavity (medulla, innermost part), which is the central cavity of bone shafts where red bone marrow and/or yellow bone marrow (adipose tissue) is stored.
A band of bone material of decreased density forming alongside the surface of the cortical bone with thickening of the periosteum. Callus formation in the affected area is common and gives the appearance of a false fracture.
An unusually happy aspect over time which can also may be observed during inappropriate situations that should be causing for example distress, fear or anger.
A deviation from the normal concentration of cobalamin (vitamin B12) in the blood. Vitamin B12 is one of the eight B vitamins.
Any deviation from the normal overall count of natural killer (NK) cells in the circulation or a deviation from the normal distribution of NK cell subtypes.
One or more brown punctate macules on the skin of the genitalia.
The occurence of an elevated body temperature of the mother during pregnancy.
Limitation of wrist and finger extension on asking patient to form a prayer sign. This is a result of progressive wrist and finger flexion contractures.
Immunohistochemistry shows accumulation of desmin protein in the muscle biopsy.
The presence of autoantibodies (immunoglobulins) in the serum that react against muscle specific kinase (anti-MuSK Ab).
The variation in the time interval between the two action potentials of the same motor unit is called jitter. This term therefore applies to increased variability in the interval between successive action potentials of the same motor unit, which is measured by electromyography (EMG).
An anomaly in the communication from a neuron to a target across a synapse in the peripheral nervous system.
The vestibulo-ocular reflex is responsible for the stabilization of the retinal image during movement. The visual vestibular ocular reflex (VVOR) or visual enhanced VOR, maintains ocular stability during head motion by generating compensatory eye movement opposite to head movement, and is a major component of visual vestibular\ninteraction. This feature is an impairment of this reflex, manifested as the combined impairment of the three compensatory eye movement reflexes, namely the vestibulo-ocular reflex (VOR), smooth pursuit (SP) and optokinetic reflex (OKR).
Dorsal extension of the big toe, sometimes accompanied by fanning of the other toes, elicited by compressing the calf muscles (a normal response is no movement of the big toe).
Increased amount of peripheral myelination.
Increase in diameter of the veins located underneath the skin of the abdomen.
The presence of autoantibodies (immunoglobulins) in the serum that react against mitochondria.
A congenital anomaly, in which the transverse process of the last lumbar vertebra (L5) fuses to the sacrum on one side or both, or to ilium, or both.
A decreased amount of dystrophin in muscle fiber tissue.
A decreased amount of collagen VI in muscle tissue. Collagen VI is a primarily associated with the extracellular matrix of skeletal muscle.
Lack of merosin protein in the muscle biopsy.
Presence of struvite (magnesium ammonium phosphate) containing calculi (kidney stones).
Divergence of digits along the A/P axis (in the plane of the palm).
An anomaly identified by motor evoked potentials (MEPs) in the leg.
An anomaly identified by motor evoked potentials (MEPs) in the arm.
Formation of excess connective tissue in the testicle.
Increased pigmentation (skin color) of the scrotum.
Presence of multiple trichilemmomata, a benign tumour originating from the outer root sheath of the hair follicle.
Increased bulk of tissue alongside the nose. The fullness can be caused by both bony and soft tissues.
Bigonial distance (lower facial width) more than 2 standard deviations below the mean (objective); or an apparently decreased width of the lower jaw (mandible) when viewed from the front (subjective).
A cranial suture that is in addition to canonical membrane-covered openings in the incompletely ossified skull of the fetus or newborn infant.
A kinked appearance of the brainstem, i.e., an exaggerated flexure.
An anomaly in the process of intramembranous ossification by which flat bones (cranial bones of the skull, i.e., the frontal, perietal, occipital, and temporal bones, and the clavicles) are formed.
A developmental anomaly in which the mastoid process fails to form and is thus found to be congenitally absent.
Failure to develop of the small intestine.
Abnormal structure of the gastrointestinal tract.
A severe form of conductive hearing impairment.
The presence of a moderate form of conductive hearing impairment.
An abnormal build up of iron (Fe) in brain tissue.
An anomaly of the suspensory ligament of lens, also known as the ciliary zonule. These ligaments represent a series of fibers connecting the ciliary body and lens of the eye, holding the lens in place.
An decreased concentration of chloride in the urine.
A condition in which two ipsilateral ureters unite and drain into the bladder at a single ureteric orifice.
Increased concentration of beta-alanine in the blood.
Muscle fibers degeneration resulting in fatty replacement of skeletal muscle fibers
An anomaly in the communication from a neuron to a target across a synapse. This is a four step process, comprising (i) synthesis and storage of neurotransmitters; (ii) neurotransmitter release; (iii) activation of postsynaptic receptors by the neurotransmitter; and (iv) inactivation of the neurotransmitter. Thus, this term is defined as an anomaly of neurotransmitter metabolic process.
A structural abnormality of the brain, which has as its parts the forebrain, midbrain, and hindbrain.
A structural abnormality of the biliary tree.
An abnormality of actions or reactions of a person taking place during interactions with others. [HPO:probinson]
A greater than normal concentration of citrate(3-) in the urine.
A decreased concentration of 5-methyltetrahydrofolate in the cerebrospinal fluid.
An abnormal regulation of the sweat glands by the sympathetic nervous system associated with abnormal perspiration.
A reduced level of the complement component C9 in circulation.
Abnormal transferrin isoform profile consistent with a type II congenital disorder of glycosylation.
Any structural anomaly of the hypothalamus.
A structural or developmental anomaly of any of the tissues involved in the genital system.
Decreased activity of coagulation factor II, which is also known as prothrombin.
An anomaly of the natural killer cell, which is a lymphocyte that can spontaneously kill a variety of target cells without prior antigenic activation via germline encoded activation receptors and also regulate immune responses via cytokine release and direct contact with other cells.
An increase in heart rate with standing of 30 beats per minute or more.
Increased width of the cross sectional diameter of the fibula.
An abnormal concentration of creatinine in the blood.
An abnormal catecholamine concentration in the blood.
A functional anomaly of the acinar gland portion of the pancreas that secretes digestive enzymes.
Increased activity of coagulation factor V, Factor V, which is activated to factor Va by means of minute amounts of thrombin (and inactivated by larger amounts of thrombin). Activated factor V (fVa) is a cofactor in the formation of the prothrombinase complex.
Absence of any measurable level of sperm in his semen, resulting from a defect in the production of spermatozoa in the testes. Can be differentiated from obstructive azoospermia on the basis of testicular biopsy.
An abnormality of the shape of the thoracic vertebra T12 such that it is wedge-shaped (narrow towards the front).
Increased length of the superior cerebellar peduncle.
Proximal mislocalization of the big toe from its normal position.
Underdevelopment (hypoplasia) of the fifth toe.
A type of anemia related to a reduction in the average life span of red blood cells in the peripheral circulation, which is normally around 120 days.
A deviation from the normal count of T cells.
Nasal tip positioned to one side of the midline.
Distance between the philtral ridges, measured just above the vermilion border, more than 2 standard deviations below the mean. Alternatively, an apparently decreased distance between the ridges of the philtrum.
Pit in the midline of the philtral groove.
Absence of the usual parallel position of philtral ridges.
Narrow ridge in the midline of the philtral groove.
Prominence of a triangular soft tissue area of the philtrum with the apex to the columella.
A reduced ability to identify precisely the site of a touch. This test is usually carried out by asking a patient, whose eyes are closed or covered, to touch the same site with a fingertip.
A type of pituitary adenoma that produces thyroid stimulating hormone (TSH).
A type of pituitary adenoma that produces gonadotropins.
Abnormal development of the neurohypophysis during embryonic growth and development.
Overproduction of adrenocorticotropic hormone (ACTH), which generally leads secondarily to overproduction of cortisol by the adrenal cortex.
An hormonally active adrenocortical adenoma, that is, an adenoma that secretes excessive amounts of adrenal hormones.
An hormonally inactive adrenocortical adenoma, that is, an adenoma that does not secrete excessive amounts of adrenal hormones.
Adrenal insufficiency secondary to a defect in corticotropin-releasing hormone production.
Type 4 total anomalous pulmonary venous connection.
Type 3 total anomalous pulmonary venous connection.
Type 2 total anomalous pulmonary venous connection.
Type 1 total anomalous pulmonary venous connection.
Supraventricular tachycardia in which an accessory pathway connecting the atria and ventricles, apart from the AV node, participates as a necessary part of a reentrant mechanism.
An uncommon congenital abnormality where the left ventricular myocardium fails to compact during embryonic development, leading to cardiomyopathy with a variable degree of ventricular dysfunction. There is genetic heterogeneity and phenotypic variability. Characteristically, there are typically deep trabeculations in the noncompacted area, with varying proportions of the LV myocardium compacted. LV noncompaction is associated with rhythm abnormalities including Wolff-Parkinson-White syndrome, conduction defects, and ventricular tachyarrhythmias.
Anomalous origin of one pulmonary artery from the ascending aorta with the contralateral pulmonary artery arising from the right ventricle.
Truncus arteriosus (single great artery leaving the base of the heart, giving rise to the coronary, pulmonary, and systemic arteries) whereby the aortic arch is hypoplastic or interrupted, and a large patent ductus arteriosus is present.
Truncus arteriosus (single great artery leaving the base of the heart, giving rise to the coronary, pulmonary, and systemic arteries) whereby one of the two pulmonary artery branched does not arise from the common pulmonary trunk, but instead from the ductus arteriosus or directly from the aorta.
Truncus arteriosus (single great artery leaving the base of the heart, giving rise to the coronary, pulmonary, and systemic arteries) with each pulmonary artery arising separate from each other on the posterior or lateral aspect of the truncus.
The left common carotid artery has a common origin with the innominate artery. [DDD:dbrown, HPO:probinson, pmid:17138027]
A congenital stenotic mitral valvular anomaly with a ring of tissue above the mitral valve.
Anomalous mitral valve arcade is diagnosed based on the following features (1) An adequately sized mitral valve orifice; (2) short, thick, and poorly differentiated chordae with direct union of the papillary muscles to the anterior leaflet; (3) narrow or nearly nonexistent spaces between the abnormal chordae; and (4) greater differentiation of the chordae attached to the posterior papillary muscle.
Sharply demarcated hyperpigmentation which is congenital.
Sharply demarcated hyperpigmentation which is congenital found in around 3-5% of the population and of no functional significance.
Generalized reduced transparency of the stroma of the cornea.
An abnormality of the medulla oblongata, the lower half of the brainstem.
An abnormally low concentration of maternal serum human chorionic gonadotropin as compared to normal values for gestational-age.
An abnormally high concentration of maternal serum human chorionic gonadotropin as compared to normal values for gestational-age.
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs that is lethal at birth.
An abnormality of myelination of nerves in the central nervous system.
Increased size of the cochlear duct, i.e., of a duct that communicates between the perilymphatic space and the subarachnoid space, and transmits a vein from the cochlea to join the internal jugular.
An abnormality of the Internal acoustic meatus, i.e., of the canal in the petrous part of the temporal bone through which the cranial nerve VII and cranial nerve VIII traverse.
Increased size of the semicircular canal.
An abnormality of the skin that is not localized to any one particular region.
A subtle unilateral cleft of the upper lip, which may appear as a small indentation.
Asymmetry of the posterior part of the skull.
Craniosynostosis involving at least 2 cranial sutures, where the exact pattern of sutures fused has not been precisely specified.
Premature synostosis of only one lambdoid suture.
Premature synostosis of both lambdoid sutures.
Synostosis affecting the right and the left coronal suture.
An abnormality of size or shape of the long bones.
A crease that connects the proximal and distal transverse palmar creases.
The absence of a phalangeal segment of a toe or hallux.
An abnormality of the hindbrain, also known as the rhombencephalon.
Increase posterolateral protrusion of the tragus.
A complete or partial duplication of the tragus; expected to lie anterior to the normal tragus.
Increased height of the tragal ridge with a shallow indentation at the apex, giving the appearance of a double peak.
Presence of some auricular structures, but none of these structures conform to recognized ear components.
Presence of all the normal ear components and the median longitudinal length more than two standard deviations below the mean.
Interruption between the ascending helix and the crus helix, allowing the ascending helix to be attached directly to the mastoid.
Positioning of the anterior surface of the ear lobe in a more coronal plane than the remainder of the ear.
Linear, circumferential indentation in the convexity of the outer surface of the helix.
Small expansion of the helical fold at the junction of the superior and descending portions of the helix.
Small defect of the helical fold that lies at the junction of the superior and descending portions of the helix.
Widening, rather than tapering, of the crus at its posterior border near the antihelix.
The anterior origin of the crus encompasses the superior margin of the tragus, the crus overrides the upper portion of the conchal cavum and ends at the antihelix.
Curving course of the crus of the helix, approaching or joining the antitragus.
Extension of the ridge of the crus helix across the ear and connection of the crus to the antihelix.
Continuum between the tragus and ascending helix, without any evidence of a posterior extension (crus) towards the concha.
Reduction in the anterosuperior prominence of the area between the bottom of the incisura and the inner margin of the antihelix.
Double rather than single peak of the antitragus.
Increased protrusion of the superior crus relative to the prominence of a normal antihelix stem.
Decreased protrusion of the superior crus relative to the prominence of a normal antihelix stem.
An abnormality of the superior crus of the antihelix is the upper cartilaginous ridge arising at the bifurcation of the antihelix that ends beneath the fold of the ascending helix, and separates the concha from the triangular fossa.
An abnormality of the inferior crus of the antihelix is the lower cartilaginous ridge arising at the bifurcation of the antihelix that ends beneath the fold of the ascending helix, and separates the concha from the triangular fossa.
Decreased protrusion of the antihelical ridge, proximal to its bifurcation, relative to the prominence of a normal helix.
Posterior curving of the antihelix from its origin at the antitragus, traveling initially almost perpendicular to the descending helix and obscuring some of the concha.
Decreased protrusion of the inferior crus relative to the prominence of the antihelix stem.
Increased protrusion of the inferior crus relative to the prominence of the antihelix stem.
Increased width of the inferred cross-section of the inferior crus.
Antihelix protrusion directed more anteriorly than laterally, forming a shelf overlying the posterior concha.
EEG discharges recorded in particular areas of the A localized (focal) abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
A sensation consistent with involvement of the autonomic nervous system, including cardiovascular, gastrointestinal, sudomotor, vasomotor and thermoregulatory functions.
Gastric duplication is a usually cystic malformation of gastrointestinal tract, usually attached to the greater curvature of the stomach and has no communication with the stomach.
An abnormality of the nasal dorsum, also known as the nasal ridge.
An abnormality of the systemic arterial tree, which consists of the aorta and other systemic arteries. [HPO:probinson]
Increased amount of chromosomal breaks in cultured blood lymphocytes or other cells induced by treatment with ionizing radiation.
An abnormality of the cerebral subcortex.
A deviation from the normal count of B cells, i.e., the cells that are formed in the bone marrow, migrate to the peripheral lymphatic system, and mature into plasma cells or memory cells.
An abnormality of fatty acid anion metabolism.
An abnormality of the fetal circulation system or fetal echocardiogram.
Periodically recurring abnormalities in the EEG.
Periodically occurring generalized periodic complexes.
An abnormal localized reduction in amplitude of the cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
An abnormal generalized reduction in amplitude of the cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Periodic lateralized epileptiform discharges (PLEDs)are periodic, lateralized, and epileptiform. PLEDs show a relatively constant interval between discharges (0.5 to 3 seconds).
Diffuse slowing of cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Focal (localized) slow activity reflects focal dysfunction, not diffuse dysfunction (i.e., encephalopathy).
A abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci).
Trophic changes is a term used to describe abnormalities in the area of pain that include primarily wasting away of the skin, tissues, or muscle, thinning of the bones, and changes in how the hair or nails grow, including thickening or thinning of hair or brittle nails.
A reduced sense of touch (tactile sensation). This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus.
A reduced ability to discriminate between different temperatures.
Abnormality of the seventh cranial nerve sometimes also referred to as the facial nerve.
Abnormality of the twelfth cranial nerve.
Abnormality of the eleventh cranial nerve.
An abormality of the fifth cranial nerve. [HPO:probinson]
Reduced bulkiness of the crease or fold of skin running from the lateral margin of the nose, where nasal base meets the skin of the face, to a point just lateral to the corner of the mouth (cheilion or commissure).
A tumor (abnormal growth of tissue) of a gonad.
Insertion of the posterior columella below the nasal base.
Positioning of a lacrimal punctum other than at the medial margins of the eyelid.
Absence of a digit or of one or more phalanges of a toe.
A developmental abnormality characterized by the absence (aplasia) of a metatarsal bone.
Abnormal prominence of the corneal nerve fibers.
Syndactyly with fusion of toes two to four.
Syndactyly with fusion of toes one to five (complete syndactyly of all toes of the foot).
Syndactyly with fusion of the fingers two to four.
A type of nuclear cataract involving congenital pulverulent disc-like opacity of the embryonal and fetal nucleus.
Mirror image duplication of digits affecting the feet.
Mirror image duplication of digits affecting the hands only.
An abnormally increased level of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
An abnormality of the formation and mineralization of any bone of the skeleton of foot.
Underdevelopment of the zygomatic bone [UBERON_0001683]. That is, a reduction in size of the zygomatic bone, including the zygomatic process of the temporal bone of the skull, which forms part of the zygomatic arch.
An abnormality of the formation and mineralization of any bone of the skeleton of hand.
Patchy (irregular) changes in bone mineral density with patches of bone showing an increased density side to side with patches that are affected by reduction of mineral density. This is sometimes referred to as a moth-eaten appearance on x-rays.
An abnormality of the formation and mineralization of an epiphysis.
Any abnormality of a metatarsal bone epiphysis.
Absence of the pituitary gland resulting from a developmental defect.
A cystic lesion originating within the brain.
The presence of developmental dysplasia of the femoral head.
Any abnormality of the proximal epiphysis of the femur.
An abnormally wavy surface or edge of the clavicles.
A soft tissue continuity in the A/P axis between two fingers that extends distally to at least the level of the proximal interphalangeal joints, or a soft tissue continuity in the A/P axis between two fingers that lies significantly distal to the flexion crease that overlies the metacarpophalangeal joint of the adjacent fingers.
Paralysis of voluntary muscles means loss of contraction due to interruption of one or more motor pathways from the brain to the muscle fibers. Although the word paralysis is often used interchangeably to mean either complete or partial loss of muscle strength, it is preferable to use paralysis or plegia for complete or severe loss of muscle strength, and paresis for partial or slight loss. Paralysis due to lesions of the principle motor tracts is related to a lesion in the corticospinal, corticobulbar or brainstem descending (subcorticospinal) neurons.
An abnormal increase in quantity or strength of fetal movements.
An abnormality of dermatoglyphs on the toes and soles, i.e., an abnormality of the patterns of ridges of the skin of sole of foot.
An abnormal limitation of knee joint mobility.
An abnormally increased length of the metacarpal bones.
A narrow segment of significantly reduced circumference of a digit.
The absence of the major creases of the palm (distal transverse crease, proximal transverse crease, or thenar crease).
Pelvic asymmetry refers to asymmetric positioning of landmarks on the two sides of the pelvis and may have a structural or functional etiology.
A structural abnormality of the interventricular septum.
Reduced length of the proximal phalanx of second toe as a result of developmental hypoplasia.
Reduced length of the middle phalanx of second toe as a result of developmental hypoplasia.
Reduced length of the distal phalanx of the second toe as a result of developmental hypoplasia.
Absence of distal phalanx of the second toe as a result of developmental aplasia.
Reduced length of one or more phalanx of second toe as a result of developmental hypoplasia.
Partial duplication of proximal phalanx of second toe.
Complete duplication of proximal phalanx of second toe.
Partial or complete duplication of the distal phalanx of second toe.
Partial or complete duplication of middle phalanx of second toe.
Partial or complete duplication of proximal phalanx of second toe.
Patchy (irregular) increase in bone density of one or more of the phalanges of the fifth toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A deviation from the normal straight form of one or more phalanges of the fifth toe.
An abnormal morphology of one or more phalanges of the fifth toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Partial or complete duplication of phalanx of fourth toe.
Patchy (irregular) increase in bone density of one or more of the phalanges of the fourth toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A deviation from the normal straight form of one or more phalanges of the fourth toe.
An abnormal morphology of one or more phalanges of the fourth toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Partial or complete duplication of phalanx of third toe.
Patchy (irregular) increase in bone density of one or more of the phalanges of the third toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A deviation from the normal straight form of one or more phalanges of the third toe.
An abnormal morphology of one or more phalanges of the third toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Partial or complete duplication of a phalanx of second toe.
Patchy (irregular) increase in bone density of one or more of the phalanges of the second toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A deviation from the normal straight form of one or more phalanges of the second toe.
An abnormal morphology of one or more phalanges of the second toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
One or more bent (flexed) joints of the fifth toe that cannot be straightened actively or passively.
One or more bent (flexed) joints of the fourth toe that cannot be straightened actively or passively.
One or more bent (flexed) joints of the third toe that cannot be straightened actively or passively.
One or more bent (flexed) joints of the second toe that cannot be straightened actively or passively.
Increased size and/or number of soft tissue folds on the palatal side of the maxillary alveolar ridge.
Distal epiphyses of the hand are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
A triangular appearance of the epiphyses of the phalanges of the fingers of the hand.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of phalanges of the fingers.
Abnormally small size of the epiphyses of the phalanges of the fingers with respect to age-dependent norms.
A pseudoepiphysis is a secondary ossification center distinct from the normal epiphysis. [HPO:curators]
Irregular radiographic opacity of the epiphyses of the phalanges of the fingers.
Fragmented appearance of the epiphyses of the phalanges of the fingers.
Bracket epiphysis refers to an abnormality in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of one or more epiphyses of the phalanges fingers.
One or more bent (flexed) joints of the first (big) toe that cannot be straightened actively or passively.
Partial/complete duplication of a proximal phalanx of toe.
Patchy (irregular) increase in bone density of one or more of the proximal phalanges of the toes. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Dissolution or degeneration of bone tissue of the proximal toe phalanx.
A deviation from the normal straight shape of a proximal phalanx of one or more toes.
An abnormal morphology of one or more of the proximal phalanges of the toes, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Absence (agenesis) or underdevelopment of one or more of the proximal phalanges of the toes.
Partial or complete duplication of a middle phalanx of toe.
Patchy (irregular) increase in bone density of one or more of the middle phalanges of the toes. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A deviation from the normal straight form of one or more middle toe phalanges.
An abnormal morphology of one or more middle phalanges of the toes, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
A partial or complete duplication of one or more distal phalanx of toe.
Patchy (irregular) increase in bone density of one or more of the distal phalanges of the toes. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A deviation from the normal straight form of one or more distal toe phalanges.
An abnormal morphology of one or more distal phalanges of the toes, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Absence or underdevelopment of the distal phalanges of the toes.
A morphological anomaly of one or more proximal phalanges of one or more toes.
Partial/complete duplication of one or more phalanx of toe.
Uneven (irregular) increase in bone density of one or more of the phalanges of the foot.
A deviation from the normal straight form of one or more toe phalanges.
An abnormal morphology of one or more phalanges of the toes, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of phalanges of the fingers. [HPO:probinson]
The presence of a supernumerary toe (not a hallux) involving the third or fourth metatarsal with associated osseous syndactyly.
Underdevelopment (hypoplasia) of a phalanx of big toe.
Underdevelopment (hypoplasia) of the distal phalanx of big toe.
Complete duplication of one or more phalanx of big toe.
Increased width of proximal phalanx of big toe.
Patchy (irregular) increase in bone density of one or more phalanges of the big toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A deviation from the normal straight form of one or more phalanges of the big toe.
An abnormal morphology of one or more phalanges of the big toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An increase in width in one or more phalanges of the big toe.
Displacement of the big toe from its normal position.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the first metacarpal bone.
This term applies if one or more of the middle phalanges of the hand are either partially duplicated, depending on severity leading to a broad or bifid appearance of the phalanges, or completely duplicated.
This term applies if one or more of the proximal phalanges of the hand are either partially duplicated, depending on severity leading to a broad or bifid appearance of the phalanges, or completely duplicated.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the distal phalanges of the hand. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
This term applies if one or more of the phalanges of the hand are either partially duplicated, depending on severity leading to a broad or bifid appearance of the phalanges, or completely duplicated.
Partial duplication of the distal phalanx of little finger, seen on x-rays as a broad and/or bifid phalanx.
Partial or complete duplication of the fifth proximal phalanx of hand.
Partial or complete duplication of the fifth middle phalanx of hand.
Partial or complete duplication of the distal phalanx of little finger.
This term applies if one or more of the phalanges of the 5th finger are either partially duplicated, depending on severity leading to a broad or bifid appearance of the phalanges, or completely duplicated.
Partial duplication of the distal phalanx of ring finger, seen on x-rays as a broad and/or bifid phalanx.
Partial or complete duplication of the fourth proximal phalanx of hand.
Partial or complete duplication of the middle phalanx of ring finger.
Partial or complete duplication of the distal phalanx of ring finger.
This term applies if one or more of the phalanges of the 4th finger are either partially duplicated, depending on severity leading to a broad or bifid appearance of the phalanges, or completely duplicated.
Partial duplication of the distal phalanx of middle finger, seen on x-rays as a broad and/or bifid phalanx.
Partial or complete duplication of the third proximal phalanx of hand.
Partial or complete duplication of the middle phalanx of middle finger.
Partial or complete duplication of the distal phalanx of middle finger.
This term applies if one or more of the phalanges of the 3rd finger are either partially duplicated, depending on severity leading to a broad or bifid appearance of the phalanges, or completely duplicated.
Partial duplication of the distal phalanx of index finger, seen on x-rays as a broad and/or bifid phalanx.
Partial or complete duplication of the middle phalanx of index finger.
Partial or complete duplication of the distal phalanx of index finger.
Partial or complete duplication of the second proximal phalanx of hand.
This term applies if one or more of the phalanges of the 2nd finger are either partially duplicated, depending on severity leading to a broad or bifid appearance of the phalanges, or completely duplicated.
Complete or partial duplication of the phalanges of the thumb. Depending on the severity, the appearance on x-ray can vary from a notched phalanx (the duplicated bone is almost completely fused with the phalanx), a partially fused appearance of the two bones (bifid), two separate bones appearing side to side, or completely duplicated phalanges (proximal and distal phalanx of the thumb and/or 1st metacarpal). In contrast to the phalanges of the digits 2-5 (proximal, middle and distal), the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
An extremely rare congenital malformation with the presence of one or more accessory nostrils, with or without accessory cartilage, located medially, above, below or laterally to the other nostrils. Unlike in polyrhinia there is no duplication of the nasal septum/cavity. Supernumerary nostril is often associated with other congenital malformations usually of the face.
The presence of a size difference between the left and right cornea.
Absence of the middle ear ossicles, malleus, incus, and stapes.
Attachment of the lobe to the side of the face at the lowest point of the lobe without curving upward.
A notched form of the helix of the ear. That is, a defect in the continuity of the helix, which may occur at any point along its length.
The presence of an abnormally prominent of the crus of the helix. That is, development of the crus helix to the same degree as an average antihelix stem or helix.
Developmental hypoplasia of the crus of the helix. That is, flatter and/or shorter crus helix than average.
An abnormal horizontal axis orientation of the crus of the helix. That is, the main axis of the crus of the helix is perpendicular to the medial longitudinal axis of the ear, instead of sloping inferoposteriorly.
An abnormality of the crus of the helix, which is the horizontal piece of cartilage located outside the ear canal that divides the upper and lower parts of the ear.
Uneven increase in bone density of the proximal phalanges of the hand.
Uneven (irregular) increase in bone density of one or more of the middle phalanges of the hand.
Increased width of the middle phalanx of finger.
Uneven (irregular) increase in bone density of the distal phalanges of the hand.
Any anomaly of distal phalanx of finger.
An anomaly of the joint that connects the upper and the lower arm.
An anomaly of one or more metaphyses of the arms.
A structural abnormality of a diaphysis of the arm.
Fusion of two or more phalangeal bones of the hand.
Increased width of the phalanges of the hand.
Complete or nearly complete soft tissue fusion of the alveolar ridges.
Presence of arachnoid cysts of the spinal canal extradurally in the epidural space.
Developmental hypoplasia of the antihelix.
A benign or malignant neoplasm (tumour) originating in striated muscle, either skeletal muscle or cardiac muscle.
Fusion of the 1st metacarpal with another bone. In contrast to the proximal phalanges of the digits 2 to 5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Fusion involving two or more metacarpal bones (A synostosis of the first metacarpal and the proximal phalanx of the thumb can also be observed, note that the first metacarpal bone corresponds to a proximal phalanx).
An abnormal union between bones or parts of bones of the fingers. The synonymous term ""symphalangism of the hand"" may be translated as fusions of bones of varying digree, that involve at least one phalangeal bone of the hand. If bony fusions are referred to as ""Symphalangism"" the fusion occurs in a proximo-distal axis. Fusions of bones of the fingers in a radio-ulnar axis are referred to as ""bony"" Syndactyly.
The presence of abnormal punctate (speckled, dot-like) calcifications in one or more of the epiphyses of the thumb.
Abnormally small size of one or more of the epiphyses of the thumb with respect to age-dependent norms.
Sclerosis of one or more of the epiphyses of the thumb, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Uneven radiographic opacity of the one or more epiphyses of the thumb.
Epiphysis of the thumb having multiple bony fragments.
Abnormally large size of the epiphyses of the thumb with respect to age-dependent norms.
A cone-shaped appearance of the epiphyses of the thumb, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
Abnormally large size of the epiphysis located at the proximal end of the distal phalanx of the thumb with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the distal phalanx of the thumb of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
Abnormality of the epiphysis of the distal phalanx of the thumb. This epiphysis is located on the proximal end of the phalanx.
Abnormal shape of one or more phalanges of the thumb such that affected phalanges resemble a triangle.
An uneven increase in bone density of one or more of the phalanges of the thumb.
A deviation from the normal straight shape of a thumb phalanx.
An abnormal morphology of one or more phalanges of the thumb, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Absence of the distal/terminal phalanx of the thumb.
Dissolution or degeneration of bone tissue of the distal phalanx of the thumb.
Absence of the proximal phalanx of the thumb. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Triangular shaped proximal phalanx of the thumb.
Dissolution or degeneration of bone tissue of the proximal phalanx of the thumb.
Any anomaly of the proximal phalanx of thumb.
Any anomaly of the distal phalanx of thumb.
Partial duplication of the first metacarpal bone.
Complete or partial duplication of the proximal phalanx of the thumb. Depending on the severity, the appearance on x-ray can vary from a notched phalanx (the duplicated bone is almost completely fused with the phalanx), a partially fused appearance of the two bones, or two separate bones appearing side to side. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Complete or partial duplication of the distal phalanx of the thumb. Depending on the severity, the appearance on x-ray can vary from a notched phalanx (the duplicated bone is almost completely fused with the phalanx), a partially fused appearance of the two bones, or two separate bones appearing side to side.
Partail or complete duplication of the first metacarpal bone.
Complete duplication of the distal phalanx of the thumb. On x-ray two separate bones appear side to side.
A structural anomaly of one or more phalanges of the thumb.
Abnormality of one or all of the epiphyses of the proximal, and distal phalanges of the thumb and/or the 1st metacarpal.
Hypoplasia (congenital reduction in size) of the proximal phalanx of the second finger.
Abnormality of the vestibulocochlear nerve, the eighth cranial nerve, which is involved in transmitting sound and equilibrium information from the inner ear to the brain.
Triangular shaped proximal phalanx of the 2nd finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Dissolution or degeneration of bone tissue of the proximal phalanx of the 2nd finger.
Increased width of the proximal phalanx of the 2nd finger.
Hypoplasia (congenital reduction in size) of the middle phalanx of the second finger, also known as the index finger.
Absence of the middle phalanx of the index (2nd) finger.
Dissolution or degeneration of bone tissue of the middle phalanx of the 2nd finger.
Hypoplasia (congenital reduction in size) of the distal phalanx of the second finger.
Fusion of the terminal/distal and middle phalanges of the 2nd finger.
Dissolution or degeneration of bone tissue of the distal phalanx of the 2nd finger.
Uneven (irregular) increase in bone density of one or more of the phalanges of the 2nd finger.
Triangular shaped phalanges of the 2nd finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Abnormality of the phalanges of the 2nd (index) finger.
Chronic loss of joint motion of the proximal interphalangeal joint of the 2nd finger due to structural changes in non-bony tissue.
Chronic loss of joint motion in the 2nd finger due to structural changes in non-bony tissue. The term camptodactyly of the 2nd finger is used if the distal and/or proximal interphalangeal joints are affected.
An abnormality of the proximal phalanx of the second finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Sclerosis of the epiphysis of the distal phalanx of the 2nd finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Absence of the epiphysis located at the proximal end of the distal phalanx of the 2nd finger.
An abnormality of the second finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Chronic loss of joint motion of the proximal interphalangeal joint of the 3rd finger due to structural changes in non-bony tissue.
Displacement of the 2nd finger from its normal position.
Hypoplasia (congenital reduction in size) of the proximal phalanx of the third finger.
Uneven (irregular) increase in bone density of one or more of the phalanges of the third finger.
Dissolution or degeneration of bone tissue of the phalanges of the 3rd finger.
Increased width of the phalanges of the 3rd finger.
Hypoplasia (congenital reduction in size) of the middle phalanx of the third finger.
Absence of the middle phalanx of the middle (3rd) finger.
Increased width of the middle phalanx of the 3rd finger.
Fusion of the terminal/distal and middle phalanges of the 3rd finger.
Dissolution or degeneration of bone tissue of the distal phalanx of the 3rd finger.
A triangular appearance of the epiphyses of the 3rd finger of the hand.
Uneven increase in bone density of one or more of the phalanges of the fourth (ring) finger.
A triangular appearance of the epiphyses of the 4th finger of the hand.
A triangular appearance of the epiphyses of the 5th finger of the hand.
Uneven increase in bone density of one or more of the phalanges of the 5th finger.
A triangular appearance of the epiphysis of the proximal phalanx of the 3rd finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
Abnormally large size of the epiphysis located at the proximal end of the proximal phalanx of the 3rd finger with respect to age-dependent norms.
A triangular appearance of the epiphysis of the distal phalanx of the 3rd finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
A triangular appearance of the epiphysis of the middle phalanx of the 3rd finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
Chronic loss of joint motion in the 3rd finger due to structural changes in non-bony tissue. The term camptodactyly of the 3rd finger is used if the distal and/or proximal interphalangeal joints are affected.
Displacement of the 3rd finger from its normal position.
Abnormality of the phalanges of the 3rd (middle) finger.
Fusion of the terminal/distal and middle phalanges of the 4th finger.
Hypoplastic/small proximal phalanx of the fourth finger.
Hypoplastic/small middle phalanx of the 4th finger, also known as the ring finger.
Absence of the middle phalanx of the ring (4th) finger.
Hypoplastic/small distal phalanx of the fourth finger.
Hypoplasia (congenital reduction in size) of the fourth finger, also known as the ring finger.
Chronic loss of joint motion of the proximal interphalangeal joint of the 4th finger due to structural changes in non-bony tissue. That is, the PIP joint of a fourth finger is bent (flexed) and cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement.
Chronic loss of joint motion in the 4th finger due to structural changes in non-bony tissue. The term camptodactyly of the 4th finger is used if the distal and/or proximal interphalangeal joints are affected.
A triangular appearance of the epiphysis of the proximal phalanx of the ring finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
An abnormality of the proximal phalanx of the fourth finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
A triangular appearance of the epiphysis of the distal phalanx of the ring finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
Increased width of the proximal phalanx of the 5th finger.
Absence or underdevelopment (hypoplasia) of the proximal phalanx of the fifth finger.
A triangular appearance of the epiphysis of the middle phalanx of the ring finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
A triangular appearance of the epiphysis of the middle phalanx of the little finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
Abnormality of the epiphysis of the distal phalanx of the fifth finger. This epiphysis is located on the proximal end of the phalanx.
Absence of the epiphyses of the metacarpal bones, which are normally located at the distal ends of the metacarpals.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the metacarpals.
Displacement of the 5th finger from its normal position.
Abnormality of the phalanges of the 4th (ring) finger.
Increased width of the middle phalanx of the 5th finger.
A triangular appearance of the epiphysis of the proximal phalanx of the little finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
A triangular appearance of the epiphysis of the distal phalanx of the little finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
Any structural anomaly of a cerebral artery. The cerebral arteries comprise three main pairs of arteries and their branches, which supply the cerebrum of the brain. These are the anterior cerebral artery, the middle cerebral artery, and the posterior cerebral artery.
This term applies to all changes in bone mineral density of the tarsal bones, which (depending on severity) can be seen on x-rays as a change in density and or structure of the bone.
Muscular atrophy involving the muscles of the upper limbs.
An abnormality of adipose tissue, which is loose connective tissue composed of adipocytes.
An abnormality of the formation and mineralization of any bone of the bony pelvis.
Decreased strength of the abdominal musculature.
Atrophy of the muscles of the pelvic girdle (also known as hip girdle), i.e., the gluteal muscles, the lateral rotators, the adductors, the psoas major and the iliacus muscle.
Aplasia or developmental hypoplasia of all or part of the middle ear.
A malformation of the laryngeal cartilage.
Abnormal enlargement of the urinary bladder.
An abnormality of the stapes, a stirrup-shaped ossicle in the middle ear.
A severe form of sensorineural hearing impairment.
The presence of sensorineural deafness with late onset.
A form of sensorineural hearing impairment with infantile onset.
A mild form of conductive hearing impairment.
A type of conductive deafness with congenital onset.
The presence of a mild form of sensorineural hearing impairment.
Permanent indentation on the posteromedial aspect of the helix that may be sharply or indistinctly delineated.
An abnormal reduction of the anterioposterior diameter of the vertebral body.
Anterior tongue-like protrusions of the vertebral bodies of the lumbar spine.
Recurrent loss, or shedding, of the nails of the fingers and toes.
Any abnormal process of ossification of the metatarsal bones, which normally are each ossified from two centers: one for the body, and one for the head (metatarsal II,III,IV, and V) and one for the body and one for the base (metatarsal I). The ossification process begins in the center of the body about the ninth week, and extends toward either extremity. The center for the base of the first metatarsal appears about the third year, and the centers for the heads of the other bones between the fifth and eighth years. They join the bodies between the eighteenth and twentieth years.
An abnormality of the formation and mineralization of any of the tarsal bones, seven bones of the foot comprising the calcaneus, talus, cuboid, navicular, and the cuneiform bones.
A reduction in immunoglobulin levels of the IgG2 subclass.
An abnormality of the mitochondria in muscle tissue.
The presence of intraceullar inclusion bodies (aggregates of stainable substances, usually proteins) in neutrophils. Cytoplasmic neutrophil inclusions (oval, basophilic) are also known as Doehle bodies.
Adrenal insufficiency secondary to a defect in the ACTH receptor.
An abnormality of thyroid physiology (HP:0002926) characterized by increased levels of thyroxine without evidence of clinical thyroid disease.
An elevated concentration of follicle-stimulating hormone in the blood.
No secondary sexual characteristics are present at puberty.
An increased concentration of ammonia in the blood not associated with symptoms such as encephalopathy.
Episodes of muscle weakness associated with reduced levels of potassium in the blood.
Defective ossification in an irregular pattern of the seven bones of the foot comprising the calcaneus, talus, cuboid, navicular, and the cuneiform bones.
Bending or curvature of a third toe in the tibial direction (i.e., towards the big toe).
Retinitis pigmentosa inversa is form of retinal degeneration characterized by areas of retinal/chorioretinal degeneration with pigment migration in the macular area (in contrast to retinitis pigmentosa which, at early disease stages, predominantly affects the retinal periphery).
A type of sutural cataract in which the opacity follows the posterior Y suture.
A dark-adapted bright flash electroretinogram in which the b-wave that is of markedly lower amplitude than the associated a-wave (source: Holder GE., Inherited Chorioretinal Dystrophies: A Textbook and Atlas; 2014; p.17; ISBN 978-3-540-69466-3].
Failure of attachment of the retina during development.
Underdevelopment of the lacrimal puncta.
Punctate opacification (reduced transparency) of the corneal stroma.
A kind of cataract that progresses with age.
The presence of distinct colors in the central (pupillary) zone of the iris than in the mid-peripheral (ciliary) zone.
A type of cataract characterized by punctate, dust-like opacities within the cortical region of the lens.
The presence of an increased number of twists and turns of retinal blood vessels (arteries, arterioles, veins, venules).
Absence of the combined rod-and-code response on electroretinogram.
An abnormality of the vestibulo-ocular reflex (VOR). The VOR attempts to keep the image stable on the retina. Ideally passive or active head movements in one direction are compensated for by eye movements of equal magnitude.
The presence of fewer than normal sweat glands.
A type of ichthyosiform erythroderma with postnatal onset.
An abnormality of somatosensory evoked potentials (SSEP), i.e., of the electrical signals of sensation going from the body to the brain in response to a defined stimulus. Recording electrodes are placed over the scalp, spine, and peripheral nerves proximal to the stimulation site. Clinical studies generally use electrical stimulation of peripheral nerves to elicit potentials. SSEP testing determines whether peripheral sensory nerves are able to transmit sensory information like pain, temperature, and touch to the brain. Abnormal SSEPs can result from dysfunction at the level of the peripheral nerve, plexus, spinal root, spinal cord, brain stem, thalamocortical projections, or primary somatosensory cortex.
An abnormality characterized by chronic impairment of the normal functioning of the axons.
A progressive degree of muscular rigidity (continuous contraction of muscles with constant resistance to passive movement).
Peripheral sensory neuropathy affecting primarily distal sensation.
A reduced sense of touch (tactile sensation) on the skin of the distal limbs. This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus.
Atrophy (wasting, decrease in size of cells or tissue) affecting the frontotemporal cerebrum.
A loss or impairment of the sensation of the relative position of parts of the body and joint position occuring at distal joints.
Chest wall pain in the area of the costochondral junctions.
Abnormal increase in density of the tissue at the costochondral junctions.
Lack of development of the glenoid fossa, also known as the glenoid cavity, which is the articular surface of the scapula that articulates with the head of the humerus.
The presence of reduced numbers of intrahepatic bile duct than normal. [HPO:probinson]
An anomaly of one or more epiphyses of a limb.
A structural abnormality of a diaphysis of the arm or leg.
An anomaly of one or more epiphyses of one or both legs.
Formation of bone in the patella later than normal.
A bending or abnormal curvature of the distal portion of the tibia.
An abnormal flattening of the distal epiphysis of femur.
The presence of abnormal punctate (speckled, dot-like) calcifications in the distal epiphysis of the ulna.
Premature tooth eruption of the permanent dentition.
A type of dental misalignment with crowded central incisors, i.e., of maxillary secondary incisor, or of maxillary central primary incisor.
Increased space between the primary teeth. Note this phenotype should be distinguished from increased space due purely to microdontia.
Abnormal shortening of all middle phalanges of toes.
The presence of a supernumerary finger (not a thumb) involving the third or fourth metacarpal with associated osseous syndactyly.
The term proximal symphalangism refers to a bony fusion of the middle and proximal phalanges of the digits of the hand, in other words the proximal interphalangeal joint (PIJ) is missing which can be seen either on x-rays or as an absence of the proximal interphalangeal finger creases.
Hypoplasia of all of the distal phalanx of finger.
Delay in the process of formation and maturation of the epiphysis of one or more phalanx.
Bilateral lack of development of the lungs.
An anomaly of epiphysis, which is the expanded articular end of a long bone that developes from a secondary ossification center, and which during the period of growth is either entirely cartilaginous or is separated from the shaft by a cartilaginous disk.
Absence (due to failure to form) or underdevelopment of the bones of the hand.
Abnormality of one or all of the epiphyses of the phalanges of the hand. Note that this includes the epiphysis of the 1st metacarpal. In contrast to the metacarpals 2-5, the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the digits 2-5 (whereas the proximal phalanx of the thumb is equivalent to the middle phalanges of the other digits).
Abnormalities affecting the phalanx of finger.
Irregularly shaped metacarpal bones of varying degree.
Rhomboid or triangular shaped 5th (little) finger middle phalanx.
An abnormally reduced degree of pneumatization (i.e., formation of air cells) in the mastoid process with respect to age-dependent norms.
Combined syndactyly and polydactyly of the great toe.
Bending or curvature of a second toe in the tibial direction (i.e., towards the big toe).
Absence of the distal interphalangeal flexion creases of the fourth finger.
A soft tissue continuity in the anteroposterior axis between the toes 2, 3, and 4.
The presence of abnormal punctate (speckled, dot-like) calcifications in one or more epiphyses during the neonatal period.
An increase in bone density affecting the basicranium (base of the skull).
An abnormal narrowing of the spinal canal related to a reduction in the interpedicular distance (i.e., the distance measured between the pedicles on frontal [coronal] imaging).
A bilateral form of triphalangeal thumb.
Underdevelopment (hypoplasia) of the third toe.
Absent ossification of the calvaria (vault of the skull).
Increased cross-section (diameter) of the long bones. Note that widening may primarily affect specific regions of long bones (e.g., diaphysis or metaphysis), but this should be coded separately.
Telangiectases (small dilated blood vessels) located near the surface of the skin in a butterfly midface distribution.
A focal type of palmoplantar keratoderma in which only certain areas of the palms and soles are affected.
An anomaly of the form or number of cells in the bone marrow.
A form of poikilocytosis in which the abnormally shaped erythrocytes have notches that results in projections that look like horns.
A reduced level of the complement component factor B in circulation.
Lack of the cartilage of the nasal septum.
Aplasia (congenital absence) of the pectoralis minor on only one side of the chest.
Developmental hypoplasia of the intestine.
Absence of gastric intrinsic factor, which is normally produced by the parietal cells of the stomach, and is required for the absorption of vitamin B12.
Recurrent episodes of decreased concentration of glucose in the blood occurring during the infantile period.
Bleeding that persists longer than the normal time following a surgical procedure.
An abnormal increase in the binding affinity of hemoglobin for oxygen.
A kind of hemolytic anemia that is induced by the ingestion of fava beans.
Short (hypoplastic) fifth metatarsal bone.
Underdevelopment of the Third metatarsal bone leading to a short (hypoplastic) third metatarsal bone.
An abnormality of the shape of the thoracic vertebra T11 such that it is wedge-shaped (narrow towards the front).
Reduced or lacking hair growth in a generalized distribution.
An anomaly in the ability to perceive and distinguish scents (odors).
An abnormality of fatty acid metabolism. [HPO:probinson]
This term applies to all changes in bone mineral density which (depending on severity) can be seen on x-rays as a change in density and or structure of the bone. Changes may affect all bones of the organism, just certain bones or only parts of bones and include decreased mineralisation as may be seen in osteoporosis or increased mineralisation and or ossification as in osteopetrosis, exostoses or any kind of atopic calicfications of different origin and distribution. The overall amount of mineralization of the bone-organ can be measured as the amount of matter per cubic centimeter of bones, usually measured by densitometry of the lumbar spine or hip. The measurements are usually reported as g/cm3 or as a Z-score (the number of standard deviations above or below the mean for the patient's age and sex). Note that measurement with this method does not reflect local changes in other bones, and as such might not be correct with regard the hole bone-organ.
An abnormality of a sulfur amino acid metabolic process.
Any abnormality of the skeletal muscle cell. Muscle fibers are subdivided into two types. Type I fibers are fatigue-resistant and rich in oxidative enzymes (they stain light with the myosin ATPase reaction), and type II fibers are fast-contracting, fatigue-prone, and rich in glycolytic enzymes (these fibers stain darkly). Normal muscle tissue has a random distribution of type I and type II fibers.
The presence of any abnormality affecting the abdominal wall.
Fusion of the second metacarpal-trapezoid.
Formation of bone tissue of trapezoid is less than expected for age.
Formation of bone tissue of trapezium is less than expected for age.
Formation of bone tissue of scaphoid is less than expected for age.
Curved appearance of the distal phalanx of the 5th (little) finger.
Abnormality of the distal phalanx of the 5th (little) finger.
Sclerosis of the epiphysis of the distal phalanx of the little finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
A cone-shaped appearance of the epiphysis of the distal phalanx of the little finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
Fusion of two or more bones of the 5th finger.
Dissolution or degeneration of bone tissue of the phalanges of the 5th finger.
An abnormality affecting one or both 5th fingers.
Fusion of two or more bones of the 4th finger.
Hypoplasia (congenital reduction in size) of the distal phalanx of the third finger.
An anomaly of the second finger, also known as the index finger.
Osteosclerosis affecting one or more bones of the hand.
Pattern of hand-wrist development does not fit the normal sequence of ossification of the individual bones of the hand.
Ossification of hand bones is less advanced than would be expected according to age-adjusted norms. [HPO:probinson]
Increase in width (breadth) of the ulnar metaphysis.
Irregularity of the normally smooth surface of the metaphysis of the ulna.
Increase in width of the diaphysis of radius.
Increase in width (breadth) of the radial metaphysis.
Irregularity of the normally smooth surface of the metaphysis of the radius.
Abnormal increase in width of the epiphyseal growth plate of the radius.
Osteosclerosis (increased density related to increased bone mass) of the ulna.
Abnormally wide bone of the skeleton of forearm.
Absence of one or more forearm bones associated with congenital failure of development.
Irregularity of the normally smooth surface of the metaphysis at the distal end of the humerus (at the elbow).
Increased width of the humeral diaphysis.
Increased width of the humeral epiphyseal growth plate.
Increased width of the humeral epiphysis.
The presence of abnormal punctate (speckled, dot-like) calcifications in the humeral epiphysis.
A delay in the process of formation and maturation of the humeral epiphysis.
Lack of formation of bone in the epiphysis of the humerus.
Increased width (breadth) of metaphyses of the arms.
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones of the arm.
Developmental hypoplasia (shortening) of middle phalanx of toe.
An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue.
An abnormality of glycoprotein metabolism related to a decreased rate of alpha-1,6-mannosylglycoprotein 2-beta-N-acetylglucosaminyltransferase activity.
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
The presence of characteristic findings of denervation on electromyography (fibrillations, positive sharp waves, and giant motor unit potentials).
A compound muscle action potential (CMAP) is a type of electromyography (EMG). CMAP refers to a group of almost simultaneous action potentials from several muscle fibers in the same area evoked by stimulation of the supplying motor nerve and are recorded as one multipeaked summated action potential. This abnormality refers to a greater than normal decrease in the amplitude during the course of the investigation. [HPO:probinson]
An increase in the amount of very-low-density lipoprotein cholesterol in the blood.
The formation of bullae (blisters) with cleavage in the lamina lucida layer of the skin.
A type of megaloblastic anemia that improves upon administration of pyrimidine supplements such as uridylic acid and cytidylic acid.
The prothrombin consumption test measures the formation of intrinsic thromboplastin by determining the residual serum prothrombin after blood clotting is complete. If there is a defect in the process, less prothrombin will be converted to thrombin than normal (less prothrombin is consumed). This test may be abnormal with conditions including deficiency of factors VIII or IX, with circulating anticoagulants, thrombocytopenia.
An increased concentration of lysine in the urine.
Decreased concentration of methylcobalamin. Methylcobalamin is a form of vitamin B12.
Increased amount of chromosomal breaks in cultured blood lymphocytes or other cells induced by treatment with DNA cross-linking agents such as diepoxybutane and mitomycin C.
An anomaly of the the pubic bone, i.e., of the ventral and anterior of the three principal components (publis, ilium, ischium) of the hip bone.
An abnormality of the acetabulum, i.e., the Acetabular part of hip bone, which together with the head of the femur forms the hip joint.
An abnormal increased in the concentration of corticotropin, also known as adrenocorticotropic hormone (ACTH), in the blood.
An abnormality of compact bone (also known as cortical bone), which forms the dense surface of bones.
An abnormality of the humerus (i.e., upper arm bone).
Abnormality of the wrist, the structure connecting the hand and the forearm.
Abnormality originating in one or more muscles, i.e., of the set of muscles of body.
An abnormality of the ilium, the largest and uppermost bone of the pelvis.
The presence of normal overall immunoglobulin levels with deficiency of specific immunoglobulins directed against bacterial polysaccharides.
Disseminated multifocal hemangiomatous or lymphangiomatous lesions of the skeleton. The lesions are lytic, well-defined, round or oval lesions within the medullary cavity, and they have an intact cortex, and manifest variable peripheral sclerosis and may exhibit endosteal scalloping.
Any anomaly of the structure of the femur.
Increased susceptibility to Klebsiella infections, as manifested by recurrent episodes of Klebsiella infection.
An increased susceptibility to Aspergillus infections, as manifested by a history of recurrent episodes of Aspergillus infections.
Abnormality of the sella turcica, a saddle-shaped depression in the sphenoid bone at the base of the human skull.
An abnormality of the midbrain, which has as its parts the tectum, cerebral peduncle, midbrain tegmentum and cerebral aqueduct.
Increased width of the superior cerebellar peduncle.
The presence of complexes of repetitive spikes and waves in EEG.
Delayed myelination in the central nervous system.
Seizures with sudden, brief (< 100 msec) involuntary single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal).
Any structural abnormality of the pyramidal tract, whose chief element, the corticospinal tract, is the only direct connection between the brain and the spinal cord. In addition to the corticospinal tract, the pyramidal system includes the corticobulbar, corticomesencephalic, and corticopontine tracts.
An abnormality of the telencephalon, which is also known as the cerebrum.
An abnormality of the viscera of the abdomen.
A structural abnormality of the central nervous system. [HPO:probinson]
A reduction in the expression of CD43 on the cell surface of lymphocytes.
Decreased cell membrane concentration of glycoprotein IIb-IIIa.
Underdevelopment (hypoplasia) of the second toe.
Bending or curvature of a toe in the tibial direction (i.e., towards the big toe).
Short distance from the end of the toe to the most distal interphalangeal crease or distal interphalangeal joint flexion point, i.e., abnormally short distal phalanx of toe.
This term applies for all abnormalities of the big toe, also called hallux.
Camptodactyly is a painless flexion contracture of the proximal interphalangeal (PIP) joint that is usually gradually progressive. This term refers to camptodactyly of one or more toes.
A form of sensorineural hearing impairment that affects primarily the higher frequencies.
An abnormality of the liver. [HPO:probinson]
An abnormality of the function of the electrical signals with which nerve cells communicate with each other or with muscles as measured by electrophysiological investigations.
An abnormality of the thenar eminence, i.e., of the muscle on the palm of the human hand just beneath the thumb.
Chronic loss of joint motion in an interphalangeal joint of a finger due to structural changes in non-bony tissue.
An abnormality of the structure or form of the diaphysis, i.e., of the main or mid-section (shaft) of a long bone.
Any abnormality of the vertebral column.
Any anomaly of the costochondral junction. The costochondral junctions are located between the distal part of the ribs and the costal cartilages, which are bars of hyaline cartilage that connect the ribs to the sternum.
Any abnormality of the clavicles (collar bones).
An abnormality of the renin-angiotensin system.
Abnormality of the adrenal glands, i.e., of the endocrine glands located at the top of the kindneys. [HPO:probinson]
An abnormality of the tricarboxylic acid cycle.
Abnormal fat accumulation in the kidneys.
Any abnormality of the thorax (the region of the body formed by the sternum, the thoracic vertebrae and the ribs).
Reduced ability to use nonverbal behavior for communication, such as eye-to-eye gaze, facial expression, body posture, and gestures.
Behavior characterized by an abnormal limitation to few interests and activities.
Abnormality of the nasal bridge, which is the saddle-shaped area that includes the nasal root and the lateral aspects of the nose. It lies between the glabella and the inferior boundary of the nasal bone, and extends laterally to the inner canthi.
A form of sensorineural deafness with either congenital onset or infantile onset, i.e., before the acquisition of speech.
An abnormality of the External acoustic tube (also known as the auditory canal).
An anomaly of the midface, which is a region and not an anatomical term. It extends, superiorly, from the inferior orbital margin to, inferiorly, the level of nasal base. It is formed by the maxilla (upper jaw) and zygoma and cheeks and malar region. Traditionally, the nose and premaxilla are not included in the midface.
The presence of a cleft in the oral cavity, the two main types of which are cleft lip and cleft palate. In cleft lip, there is the congenital failure of the maxillary and median nasal processes to fuse, forming a groove or fissure in the lip. In cleft palate, there is a congenital failure of the palate to fuse properly, forming a grooved depression or fissure in the roof of the mouth. Clefts of the lip and palate can occur individually or together. It is preferable to code each defect separately.
Extra fold of tissue extending from the alveolar ridge to the inner surface of the upper or lower lip.
Any abnormality of the palate, i.e., of roof of the mouth.
Any abnormality of the gingiva (also known as gums).
An abnormality of the ovary. [HPO:probinson]
An abnormal functionality of the genital system.
An abnormality of the female external genitalia.
Ambiguous genitalia in an individual with XY genetic gender.
Combined syndactyly and polydactyly of the foot on the lateral side (i.e., on the side of the little toe).
Craniosynostosis of all calvarial sutures.
An abnormally advanced degree of pneumatization (i.e., formation of air cells) in the mastoid process with respect to age-dependent norms.
An abnormality of the calf, i.e. of the posterior part of the lower leg.
Increased concentration of uracil in the urine.
Any abnormality of the parietal bone of the skull.
Presence of a lipoma in the region of the sacrum.
Stop of growth at the epiphyseal plate the hyaline cartilage plate in the metaphysis at one or more long bones in the fibula, at an earlier than normal age, resulting in growth arrest and shortening of the involved bone.
A deviation from the normal contents of the platelet alpha granules, which normally contain adenosine triphosphate (ATP), adenosine diphosphate (ADP), serotonin, calcium, and pyrophosphate, which are secreted when platelets are activated.
An anomaly of the invaginations of the surface membrane that form the open canalicular system (OCS). The OCS serve as the pathway for transport of substances into the cells and as conduits for the discharge of alpha granule products secreted during the platelet release reaction.
An elevated concentration of 3,3',5-triiodo-L-thyronine in the blood.
Absence or underdevelopment of the cerebral white matter.
An abnormality of the function of the middle ear.
Abnormal morphology of collagen fibers in cartilage. In cartilage, collagen II, actually a collagen II:IX:XI heterofibril, is by far the most important type of collagen. A number of abnormalities may be appreciated by electron micrography or biochemical investigations, including sparse collagen fibers in the cartilage matrix. [HPO:probinson, pmid:11879535, pmid:7757081, pmid:9468540]
An abnormality of the process of DNA repair, that is, of the process of restoring DNA after damage.
A hamartoma (disordered proliferation of mature tissues) of the conjunctiva.
An abnormally increased sensitivity to the effects of ionizing radiation.
The presence of developmental dysplasia of the vertebral column.
An abnormality of carnitine metabolism. [HPO:gcarletti]
A deviation from the normal count of CD4-positive, CD25-positive, alpha-beta regulatory T cells.
Abnormality of the midnasal cavity which includes the cavity between the nares and the choanae.
An abnormal increase in the length of the tibia.
Increased length of the distal phalanx of finger.
An abnormality of the palpebral conjunctiva.
Absence of a localized portion of the ear that cannot be described by a more precise term (e.g., absent ear lobe).
Increased vertical distance from the vermillion border of the lower lip to the inferior-most point of the chin.
Any complex of structural, architectural, contractile or electrophysiological changes affecting the atria with the potential to produce clinically relevant manifestations.
The presence of premature sister chromatid segregation.
A tumor (abnormal growth of tissue) of adipose tissue.
An abnormal size of the palpebral fissures for example unusually long or short palpebral fissures.
The presence of an abnormal shape of the palpebral fissure.
A type of dysharmonic skeletal maturation in which there is an acceleration in skeletal maturation whose degree differs markedly in different bones.
Decreased width of the foramen obturatorium. The foramen obturatorium (also known as the obturator foramen) is a hole located between the ischium and pubis bones of the pelvis.
An abnormality of the medulla of the kidney.
An elevation in bone density in the distal phalanx of the third toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in the middle phalanx of the third toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in the proximal phalanx of the third toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation in bone density in the proximal phalanx of the second toe. Sclerosis is normally detected on a radiograph as an area of increased opacity.
An elevation of bone density in the proximal phalanx of the thumb.
An elevation of bone density in the distal phalanx of the thumb.
An abnormality of the xiphoid process of the sternum.
An abnormality in the size of the ocular globe (eyeball).
An abnormality in the placement of the ocular globe (eyeball).
Increased length and width of one half of the tounge.
An abnormality of the palm, that is, of the front of the hand.
Increase in bone density of the vertebral body.
Decreased ossification of the vertebral bodies.
Absence or underdevelopment of the eyebrow. [HPO:probinson]
An increased susceptibility to cutaneous abscess formation, as manifested by a medical history of recurrent cutaneous abscesses.
Vitamin K is a fat-soluble vitamin with a role in promoting the coagulation cascade.
An abnormal increase in the total number of T cells detected in the blood.
A tumor (abnormal growth of tissue) of the nail.
Congenital absence or underdevelopment of the colon.
An abnormality of the region around the nails of the fingers or toes.
A congenital underdevelopment (aplasia or hypoplasia) of the pancreas.
The absence of the normal curvature of the vertebral column.
Lack of separation of the upper and lower lips.
A rare birth defect in women where the urethra and vagina both open into a common channel.
A structural anomaly of the vessel that contains or conveys lymph fluid.
An anomaly of the lymphatic system, a network of lymphatic vessels that carry a clear fluid called lymph unidirectionally towards either the right lymphatic duct or the thoracic duct, which in turn drain into the right and left subclavian veins respectively. [HPO:probinson]
An anomaly of the joint between the trochlear notch of ulna and the trochlea of humerus, which is part of the elbow joint.
Abnormal eating habit with excessive or insufficient consumption of food or any other abnormal pattern of food consumption.
An abnormality of the lumbar vertebral column.
An abnormality of the thoracic vertebral column.
An abnormality of the microglial cells. They are also known as brain-resident macrophages or hortega cells.
One of the three types of glia cells that, with the nerve cells, compose the central nervous system and are characterized by sheetlike processes that wrap around individual axons to form the myelin sheath of nerve fibers.
An abnormality of Sharpey's fibers (bone fibers, or perforating fibers), which are a matrix of connective tissue consisting of bundles of strong collagenous fibres connecting periosteum to bone.
Failure to close of the chest and abdominal wall likely caused by the failure of the ventral wall to close during week 4 of development.
A paraganglioma (a neuroendocrine neoplasm) originating in a carotid artery.
A congenital malformation with a cleft (gap or opening) in the midline of the face.
The presence of a neoplasm of the testis with origin in a Leydig cell.
Death between the age of 16 and 40 years.
The presence of many cysts in the glomerulus of the kidney related to dilatation of the Bowman's capsule.
A medical history of exposure during the fetal period to hyperphenylalaninemia because the mother had phenylketonuria with inadequate control during pregnancy.
Leukocyturia without bacterial growth upon urine culture.
Presence of small, permanently dilated blood vessels near the surface of the skin, visible as small focal red lesions.
An abnormal enlargement of the renal calices, the system of ducts of the kidney that collect urine.
Telangiectasia of the mucosa, the mucous membranes which are involved in absorption and secretion that line cavities that are exposed to the external environment and internal organs.
Triplication of the spinal cord - extremely rare.
Coexistence of two hemicords, at variable levels, causing splaying of the posterior vertebral elements. Results in neurological deficits in lower limb or perineum.
Difference in length or size between the right and left arm.
A growth pattern that displays an abnormal difference between the left and the right side.
An anomaly of the supraorbital portion of the frontal bones.
The appearance of abnormal valgus deformity in one knee in association with varus deformity in the other.
An abnormality of phosphate homeostasis or concentration in the body.
An anomaly in the metabolism of a vitamin.
A decreased concentration of ammonia in the blood.
Contractures of one ore more joints of the feet meaning chronic loss of joint motion due to structural changes in non-bony tissue.
Patchy (irregular) increase in bone density of the distal phalanx of the fifth toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Uneven increase in bone density of the distal phalanx of the fourth toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Uneven increase in bone density of the proximal phalanx of the fifth toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Uneven increase in bone density of the proximal phalanx of the fourth toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Uneven increase in bone density of the middle phalanx of the fifth toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
Uneven increase in bone density of the middle phalanx of the fourth toe. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A deviation from the normal straight form of the distal phalanx of the fifth toe.
A deviation from the normal straight form of the distal phalanx of the fourth toe.
A deviation from the normal straight form of the distal phalanx of the third toe.
A deviation from the normal straight form of the proximal phalanx of the fifth toe.
A deviation from the normal straight form of the proximal phalanx of the fourth toe.
A deviation from the normal straight form of the proximal phalanx of the third toe.
A deviation from the normal straight form of the middle phalanx of the fifth toe.
A deviation from the normal straight form of the middle phalanx of the fourth toe.
A deviation from the normal straight form of the middle phalanx of the third toe.
An abnormal morphology of the distal phalanx of the fifth toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An abnormal morphology of the distal phalanx of the fourth toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An abnormal morphology of the distal phalanx of the third toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An abnormal morphology of the proximal phalanx of the fifth toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An abnormal morphology of the proximal phalanx of the fourth toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An abnormal morphology of the proximal phalanx of the third toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An abnormal morphology of the middle phalanx of the fifth toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An abnormal morphology of the middle phalanx of the fourth toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An abnormal morphology of the middle phalanx of the third toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Complete duplication of proximal phalanx of third toe.
Absence (agenesis) or underdevelopment of one or more of the proximal phalanges of the 5th toe.
Absence (agenesis) or underdevelopment of one or more of the proximal phalanges of the 4th toe.
Absence (agenesis) or underdevelopment of one or more of the proximal phalanges of the 3rd toe.
The joint between the second metatarsal and the proximal phalanx of the 5th toe cannot be straightened actively or passively.
The joint between the second metatarsal and the proximal phalanx of the 4th toe cannot be straightened actively or passively.
The joint between the second metatarsal and the proximal phalanx of the 3rd toe cannot be straightened actively or passively.
The joint between the second metatarsal and the proximal phalanx of the 2nd toe cannot be straightened actively or passively.
The distal interphalangeal joint of the 5th toe cannot be straightened actively or passively.
The distal interphalangeal joint of the 4th toe cannot be straightened actively or passively.
The distal interphalangeal joint of the 3rd toe cannot be straightened actively or passively.
Fusion involving carpal and metacarpal bones.
Juvenile aseptic necrosis comprises a group of orthopedic diseases characterized by interruption of the blood supply of a bone, followed by localized bony necrosis most often of the epiphyses of bones of children or teenagers.
Nuclear or cytoplasmic aggregates of stainable substances within cells of the brain.
Cerebral inflammation involving a granulomatous response, i.e., a non-specific inflammatory response involving granulomas, defined as a compact organized collection of mature mononuclear phagocytes including epithelioid and giant cells.
The presence of a germ cell tumor of the cerebrum.
Atrophy of one side of the brain, characterized by findings including thinning of the cerebral cortex, reduced volume of the cerebral white matter with abnormal myelination, and enlargement of the ispilateral fourth ventricle.
The presence of inclusion bodies within the nucleus of muscle cells. Inclusion bodies are aggregates (deposits) or stainable material, usually misfolded proteins.
The presence of inclusion bodies within the cytoplasm of muscle cells. Inclusion bodies are aggregates (deposits) or stainable material, usually misfolded proteins.
The presence of amyloid deposition in the nerves of the peripheral nervous system.
The presence of spontaneous bursts of rapidly firing potentials that recur at regular intervals of 2-10 per second and are unaffected by voluntary effort. This is an electromyographic (EMG) finding.
The presence of reduced conduction velocity of motor nerves on electromyography.
An electromyographic finding associated with erratic or absent neuromuscular transmission with erratic, moment-to-moment changes in the shape of the motor unit potential (MUP).
High frequency discharges in electromyography (EMG) that vary in amplitude and frequency, waxing and waning continuously with firing frequencies ranging from 150/second down to 20/second and producing a sound that has been referred to as a dive bomber sound.
Continuous electromyographic activity of motor units at rest, i.e., without voluntary movement of the muscles.
Benign congenital lesions of the periauricular soft tissue consisting of a blind-ending narrow tube or pit.
A small, skin-lined tract that leads from the surface to deep within the tissues. []
Hyponasal speech is when there is an abnormally reduced nasal airflow during speech often in a setting of nasal obstruction or congestion.
An abnormality resulting from a defect or disruption of dorsoventral patterning that normally happens during early development of the limbs. A disruption of the normal development of the dorsoventral axis may lead to a variable spectrum of different phenotypic abnormalities that may affect the nails and or palmar and dorsal side of the hands and/or feet, ultimately changing the normal dorsoventral appearance of the affected limbs.
Depression located paramedially on the vermilion of a lip.
Depression located on the vermilion of the upper lip, usually paramedian.
Calcium deposition affecting the Meninges.
Ectopic respiratory epithelium presenting as a superficial lesion in the skin usually localised unilateral in the skin of the forearm and associated with ipsilateral hand malformations.
An abnormal union between bones or parts of bones of the upper limbs.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the proximal phalanx of the 5th toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the middle phalanx of the 5th toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the distal phalanx of the 5th toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the proximal phalanx of the 4th toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the middle phalanx of the 4th toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the distal phalanx of the 4th toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the proximal phalanx of the 3rd toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the middle phalanx of the 3rd toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the distal phalanx of the 3rd toe.
Abnormality of the growth of the axillary hair. Axillary hair is part of the secondary sexual hair, which normally ensues during puberty.
Abnormality of the growth of the pubic hair. Pubic hair is part of the secondary sexual hair, which normally ensues during puberty.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the proximal phalanx of the 2nd toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the middle phalanx of the 2nd toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the distal phalanx of the 2nd toe.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the 5th toe.
Epiphyses of the 5th toe are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the 4th toe.
Epiphyses of the 4th toe are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the 3rd toe.
Epiphyses of the 3rd toe are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the 2nd toe.
Epiphyses of the 2nd toe are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
An Abnormality of cortical bone leading to an abnormal thickness of the cortex of affected bones.
Scalp hair whose growth is slower than normal.
Accessory ectopic thyroid tissue arising from remnants of the thyroglossal duct anywhere along the path of the thyroglossal duct tract.
A form of hypersociability that presents as mostly inappropriate people-orientation and friendliness towards others on an inadequate level which might go as far as being dangerous considering for example young children following strangers without restriction.
A type of stereotypic behavior in which the affected individual repeatedly waves the hands up and down.
A cataract which is found in the back outer layer of the lens. This type often develops more rapidly.
An early onset of puberty, in this case early does not refer to precocious.
An increased amount of 3-aminoisobutyric acid in the urine.
Defect or defects of the morphogenesis of the left heart identifiable at birth.
Aplasia (absence) of the lymphatic vessels.
An increased amount of carboxylic acid in the urine.
An increased amount of 3-hydroxybutyric acid in the urine.
An abnormality of the composition of sweat or the levels of its components.
A tumor (abnormal growth of tissue) of the outer ear.
Lack of skin pigmentation (coloring) of the chest.
An increased number of Absence of CD4-positive, CD25-positive regulatory T cells. [HPO:probinson]
A structural anomaly of a CD4-positive, CD25-positive, alpha-beta T cell. These cells are regulatory T cells.
A structuraly anomal of T cells that express an alpha-beta T cell receptor.
A reduced ability of the skin of the fingertips to wrinkle when exposed to stimuli such as soaking in water or application of EMLA cream (the fingertip remains smooth).
The presence of cartilage cells (chondrocytes) that are substantially increased in size and contain more than one nucleus and are located within the resting zone of the epiphyseal cartilage.
An anomaly in the number of osteoclasts, bone-resorbing cells that develop from macrophages.
An anomaly in the number of macrophages.
Fissure within the spinal cord of the neck.
Underdevelopment of the vertebral artery on both sides.
An anomaly of the vertebral artery, the major artery of the neck that originates from the subclavian artery and merges to form the single midline basilar artery in a complex called the vertebrobasilar system.
An increase in the vertical distance between adjacent vertebral bodies, observed as an increase in the intervertebral disc space.
An anomalous structure of the periosteum, i.e., of the membrane that covers the outer surface of bones.
Displacement or malalignment of one or more joints in the lower extremity (leg).
Displacement or malalignment of one or more joints in the upper extremity (arm).
The presence of a splayed (i.e.,flared) metaphyseal segment of the distal fibula.
The presence of a splayed (i.e.,flared) metaphyseal segment of the distal tibia.
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones of the leg.
The presence of 11 instead of the normal 12 thoracic vertebrae.
A deviation from the normal number of vertebrae in the spinal column.
Underdevelopment of the anterior commissure.
An anomaly of the anterior commissure, a bundle of nerve fibers that connect the two cerebral hemispheres across the midline. The anterior commissure plays a role in pain sensation and contains decussating fibers from the olfactory tracts.
Presence of only 10 (instead of the usual 12) pairs of ribs.
An anomaly of the metaphysis of the distal femur (close to the knee).
Irregularity of the normally smooth surface of a metaphysis of a fibula.
Irregularity of the normally smooth surface of a metaphysis of a tibia.
Irregularity of the normally smooth surface of one or more metaphyses of a bone of the leg.
Atrophy of the superior cerebellar peduncle.
Abnormal splayed configuration (spreading out) of the superior cerebellar peduncle.
A form of macrogloassia (increased size of the tongue) characterized by a broad based root of the tongue but a small tongue tip, giving the appearance of a triangle.
Fusion of cervical vertebrae at C3 and C4, caused by a failure in the normal segmentation or division of the cervical vertebrae during the early weeks of fetal development.
Underdeveloped pedicle of the fifth lumbar vertebra.
Abnormal morphology of a vertebral pedical.
Scrotum in a position other than the usual position inferior to the base of the penis.
Additional scrotum, or part of a scrotum in an abnormal location.
Decrease in the activity of adenosine deaminase (ADA), an enzyme involved in purine metabolism, within erythrocytes. ADA is involved in the catabolism of adenosine.
An altered ability of any enzyme to act as catalysts within erythrocytes. This term includes changes due to altered levels of an enzyme.
2,3-diphosphoglycerate (2,3-DPG) controls the movement of oxygen from red blood cells to tissues. Anemia is usually accompanied by an increased level of 2,3-DPG in order to promote tissue oxygenation. This term refers to an inappropriate low 2,3-DPG concentration in erythrocytes.
Increase in the activity of adenosine deaminase (ADA), an enzyme involved in purine metabolism, within erythrocytes. ADA is involved in the catabolism of adenosine.
Increased growth of callus, the bony and cartilaginous material that forms a connecting bridge across a bone fracture during fracture healing.
Deposition of calcium salts in the fibrous sheet that connects the radius and the ulna.
Distance between left and right side of the flaccid penis at the attachment to the skin above the pubic symphysis more than 2 standard deviations above the mean for age.
Penile width more than 2 standard deviations (SD) below the mean for age. Alternatively circumference of the flaccid penis more than 2 SD below the mean for age. Alternatively, apparently decreased penile width for age.
Localized or generalized decreased genital pigmentation.
Localized or generalized increased genital pigmentation.
The presence of multiple polyps in the small intestine.
The presence of multiple polyps in the large intestine.
A reduced ability of a T cell population to expand by cell division following T cell activation.
Complete lack of mature B cells, that is, of B cells that have left the bone marrow.
Complete lack of memory B cells, that is, of mature B cell type that is long-lived, readily activated upon re-encounter of its antigenic determinant, and has been selected for expression of higher affinity immunoglobulin.
The term splanchnic vein thrombosis encompasses Budd-Chiari syndrome (hepatic vein thrombosis), extrahepatic portal vein obstruction (EHPVO), and mesenteric vein thrombosis; the word splanchnic is used to refer to the visceral organs (of the abdominal cavity).
The occurence of fever in a mother during the first trimester of pregnancy.
Underdevelopment of the musculature of the upper arm, which may include the deltoid, the triceps, the biceps, and the brachioradialis.
Abnormalities of the overall muscle bulk based on clinical observation.
An increased CPK level more than 50X above the upper normal level.
An increased CPK level between 4X and 50X above the upper normal level.
Elevated glycogen content in the sarcoplasm (cytoplasm) of muscle fibers.
An increased amount of glycogen in muscle tissue found specifically in lysosomes.
The presence of disorganized areas called cores in the center of muscle fibers. There is a typical appearance of the biopsy on light microscopy, where the muscle cells have cores that are devoid of mitochondria and specific enzymes. Cores are typically well demarcated and centrally located, but may occasionally be multiple and of eccentric.
A deviation from normal in the expression of valosin-containing protein in muscle tissue. Valosin-containing protein an ubiquitously expressed multifunctional 100-kD protein that is a member of the AAA+ (ATPase associated with various activities) protein family.
Immunohistochemistry shows accumulation of myotilin protein in the muscle biopsy.
A deviation from normal in the expression of myotilin in muscle tissue. Myotilin is a 57kD cytoskeletal protein.
A deviation from normal in the expression of desmin in muscle tissue. Desmin is an 53-KDa protein.
Difficulty in performing the correct execution of limbs movements in absence of motor impairment.
Reduction of goal-directed behaviors linked to the impairment in frontal executive functions (planning of an action for example).
Reduced velocity and acceleration in the pupillary light response.
The presence of autoantibodies (immunoglobulins) in the serum that react against voltage-gated calcium channels.
The presence of autoantibodies (immunoglobulins) in the serum that react against the acetylcholine receptor.
A compound muscle action potential (CMAP) is a type of electromyography (EMG). CMAP refers to a group of almost simultaneous action potentials from several muscle fibers in the same area evoked by stimulation of the supplying motor nerve and are recorded as one multipeaked summated action potential. This abnormality refers to an abnormal increase in the amplitude during the course of the investigation.
Lack of improvement of muscle strength in response to administration of an acetylcholine esterase inhibitor.
Improvement of muscle strength in response to administration of an acetylcholine esterase inhibitor.
Specific drugs interfere selectively with the different cellular mechanisms involved in neuromuscular transmission (synthesis, storage, release, action and inactivation of transmitter). The response of a patient to a specific drug can therefore be useful information for the differential diagnosis.
A type of weakness of a skeletal muscle of proximal part of a limb that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
A type of weakness of a skeletal muscle in the neck that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
A type of weakness of a skeletal muscle of distal part of a limb that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
A type of weakness of skeletal muscle that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
A type of weakness of the muscles involved in breathing (respiration) that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
A type of weakness of the muscles involved in swallowing that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
A type of weakness of the muscles involved in speech that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
A type of weakness of the muscles involved in chewing that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
A type of weakness of the bulbar muscles (muscles of the mouth and throat responsible for speech and swallowing) that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
Reduced muscle tone of oral musculature. In infants, this feature may be associated with difficulties in breast feeding, and may affetc the latch, jaw motions, tongue placement, lip seal, suck/swallow/breathe pattern and overall feeding behavior.
Tremor classified by the affected body part.
An isometric tremor occurs with muscle contraction against a rigid stationary object (e.g., when making a fist).
Loss of strength in all four limbs. Tetraplegia refers to a complete loss of strength, whereas Tetraparesis refers to an incomplete loss of strength.
An anomaly in the magnitude of the action potential along a peripheral nerve, that is, of the rapid rise and fall of the electrical membrane potential of the nerve.
Loss of myelin from peripheral nerves in a pattern that differs between right and left.
Elevated thickness of the myelin sheath of peripheral nerves, in a regular and concentric fashion.
Congenital absence of the myelin sheath on a nerve.
Presence of a pseudoaneurysm in the artery that supplies the gallbladder and cystic duct with blood. A pseudoaneurysm, also known as a false aneurysm, forms when blood leaks through a breach of the arterial wall but is contained by the adventitia or surrounding perivascular soft tissue.
The presence of an increased number of twists and turns of the retinal artery. [HPO:probinson]
Complete lack of abdominal sounds as assayed by examination of the abdomen with a stethoscope.
An anomaly in the placement or shape of the hairline (trichion) on the back of the head (neck), that is, the border between skin on the back of the head that has head hair and that does not.
Recurrent or excessive bleeding from the mouth.
An abnormal high amount of bleeding following the procedure of taking a blood sample.
An abnormally increased degree of bleeding following a superfical injury to the surface of the skin.
Bleeding that persists for a longer than usual time following circumcision.
Abnormal response to ristocetin as manifested by increased aggregation of platelets upon addition of low-dose ristocetin to platelet-rich plasma.
Lack of intermediate von Willebrand Factor multimers on gel electrophoresis.
Complete absence of all von Willebrand factor multimers.
Detection of abnormal ultra-large von Willebrand factor multimers.
Absence of large von Willebrand Factor multimers on gel electrophoresis.
Deviation from the normal von Willebrand factor multimer pattern.
Reduced ability of von Willibrand factor (vWF) to bind collagen. Abnormal response to collagen as manifested by reduced or lacking ability of plasma von WIllebrand Factor to bind collagen. An ELISA-based assay is typically used; the test is sensitive to loss of von Willebrand Factor high molecular weight multimers.
Abnormal response to ristocetin as manifested by reduced or lacking aggregation of platelets upon addition of ristocetin to platelet-poor plasma.
An anomaly of the inner mucous membrane of the uterus.
A decreased amount of lamin A/C in muscle tissue. This feature can be shown by immunohistochemistry of Western blotting of muscle tissue.
A deviation from the normal amount of lamin A/C in muscle tissue. The LMNA gene gives rise to at least three splicing isoforms including the two main isoforms, lamin A and lamin C. These are constitutive components of the fibrous nuclear lamina and have different roles, ranging from mechanical nuclear membrane maintenance to gene regulation.
Immunohistochemistry reveals reduced perlecan protein in the muscle biopsy. Perlecan is a basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) also known as heparan sulfate proteoglycan 2 (HSPG2).
Western blot reveals reduced calpain-3 protein in the muscle biopsy tissue.
Western blot shows complete lack of calpain-3 protein in the muscle biopsy tissue.
A deviation from normal in the amount of calpain-3 in muscle tissue. Calpains are intracellular nonlysosomal cysteine proteases modulated by calcium ions. A typical calpain is a heterodimer composed of two distinct subunits, one large (over 80 kDa) and the other small (30 kDa). While only one gene encoding the small subunit has been demonstrated, there are many genes for the large one. CAPN3 is similar to ubiquitous Calpain 1 and 2 (m-calpain and micro-calpain), but contains specific insertion sequences (NS, IS1 and IS2). Calpains cleave target proteins to modify their properties, rather than breaking down the substrates.
Immunohistochemistry reveals reduced emerin protein in the muscle biopsy.
Immunohistochemistry shows complete lack of emerin protein in the muscle biopsy.
A deviation from normal of the amount of the inner nuclear membrane protein emerin in muscle tissue.
Immunohistochemistry shows complete lack of dysferlin protein in the muscle biopsy.
A deviation from normal in the expression of dysferlin in muscle tissue. Dysferlin is an ubiquitous 230-KDa transmembrane protein involved in calcium-mediated sarcolemma resealing.
A deviation from normal of muscle alpha-dystroglcan expression. Alpha-dystroglycan is a heavily glycosylated peripheral-membrane component of the dystrophin-associated glycoprotein complex (DAPC), which, in addition to laminin alpha2, binds perlecan and agrin in the extracellular matrix, whereas beta-dystroglycan, derived from the same gene, is a transmembrane protein that links to dystrophin intracellularly.
Immunohistochemistry shows complete lack of delta sarcoglycan protein in the muscle biopsy.
Immunohistochemistry shows complete lack of gamma sarcoglycan protein in the muscle biopsy.
Immunohistochemistry reveals reduced gamma sarcoglyan protein in the muscle biopsy.
Immunohistochemistry reveals reduced beta sarcoglycan protein in the muscle biopsy.
Immunohistochemistry shows complete lack of beta sarcoglycan protein in the muscle biopsy.
Deviation from normal in the amount of delta sarcoglycan in muscle. The alpha, beta, gamma, and delta sarcoglycans are components of the dystrophin-complex. They are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a cluster of conserved cysteines.
Deviation from normal in the amount of gamma sarcoglycan in muscle. The alpha, beta, gamma, and delta sarcoglycans are components of the dystrophin-complex. They are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a cluster of conserved cysteines.
Deviation from normal in the amount of beta sarcoglycan in muscle. The alpha, beta, gamma, and delta sarcoglycans are components of the dystrophin-complex. They are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a cluster of conserved cysteines.
A decreased amount of alpha sarcoglycan in muscle. Immunohistochemistry reveals reduced alpha sarcoglycan protein in the muscle biopsy.
Lack of alpha sarcoglycan in muscle. Immunohistochemistry reveals absent alpha sarcoglycan protein in the muscle biopsy.
Deviation from normal in the amount of alpha sarcoglycan in muscle. The alpha, beta, gamma, and delta sarcoglycans are components of the dystrophin-complex. They are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a cluster of conserved cysteines.
Immunohistochemistry reveals reduced alpha dystroglycan protein in the muscle biopsy. Alpha-dystroglycan is a heavily glycosylated peripheral-membrane component of the dystrophin-associated glycoprotein complex (DAPC), which, in addition to laminin alpha2, binds perlecan and agrin in the extracellular matrix, whereas beta-dystroglycan, derived from the same gene, is a transmembrane protein that links to dystrophin intracellularly.
Lack of dystrophin in muscle tissue. Immunohistochemistry reveals absent dystrophin protein in the muscle biopsy.
A deviation from normal in the amount of dystrophin in muscle fiber tissue. Dystrophin is located at the muscle sarcolemma in a membrane-spanning protein complex that connects the cytoskeleton to the basal lamina.
A reduced amount of laminin beta 1 in muscle fiber tissue. Laminin 2 is a major component of the basal lamina of skeletal muscle cells. It is a heterotrimer composed of 3 chains: merosin (laminin alpha 2 chain), beta 1, and gamma 1.
A deviation from normal of the amount of laminin beta 1 in muscle fiber tissue. Laminin 2 is a major component of the basal lamina of skeletal muscle cells. It is a heterotrimer composed of 3 chains: merosin (laminin alpha 2 chain), beta 1, and gamma 1.
A reduced amount of merosin in muscle fibers. This feature is usually assessed by immunohistochemical examination of muscle biopsy tissue.
An anomalous amount of merosin in muscle fibers. Merosin is a basement membrane-associated protein found in placenta, striated muscle, and peripheral nerve.
An anomalous amount of protein present in or on the surface of muscle fibers. This feature may be appreciate upon immunohistochemical investigation of muscle biopsy tissue.
An anomalous concentration of testosterone in the blood.
Decreased concentration of lactate in the cerebrospinal fluid.
Abnormal concentration of lactate in the cerebrospinal fluid.
Abnormal consumption of fluids with excessive or insufficient consumption of fluid or any other abnormal pattern of fluid consumption.
Multiple pointlike areas of high T2 signal observed upon magnetic resonance imaging of the periventricular cerebral white matter.
An abnormal reduction in mitochondrial DNA content of cells.
When viewed on end (with the tip of the toe pointing toward the examiner's eye) the curve of the toenail forms a tighter curve of convexity.
A morphological anomal of the lateral ventricle.
A congenital anomaly characterized by a joining (fusion) of two or more lumbar vertebral bodies with one another.
A congenital anomaly characterized by a joining (fusion) of two or more thoracic vertebral bodies with one another.
Inability of the kidneys to produce either concentrated or dilute urine.
An incomplete absence of the foot, with no bony elements distal to the tarsals, but with preservation of some or all of the tarsals.
Significant reduction in both length and girth of the toe compared to the contralateral toe, or alternatively, compared to a typical toe size for an age-matched individual.
The absence of all phalanges of a digit and the associated metacarpal /metatarsal.
A morphological anomaly of the nasal cartilage.
Flattening instead of curving or rounded superior helix, allowing the superior helix to run more horizontally than usual.
Small indentation in the lower part of the ascending helix, concha, or in the crus helix.
Small cartilaginous prominence on the posterior concha.
The persistent of recurrent difficulty, delay in, or absence of attaining orgasm following sufficient sexual stimulation and arousal. []
Abnormality in single fiber EMG recording, a technique that allows identification of action potentials (APs) from individual muscle fibers.
A condition in which the eyelids do not close to cover the eye completely.
Abnormality observed upon electromyography when nerve studied is electrically stimulated six to ten times at 2 or 3 Hertz.
An involuntary and painless delay in the relaxation of skeletal muscle following contraction or electrical stimulation that is induced by exposure to cold.
Slowed relaxation of muscles in the arm.
Slowed relaxation of muscles in the leg.
Slowed relaxation of muscles in the jaw.
Slowed relaxation of muscles in the face.
An anomaly identified by motor evoked potentials (MEPs). MEPs are measured following single-pulse or repetitive transcranial magnetic stimulation and can be used for the assessment of the excitability of the motor cortex and the integrity of conduction along the central and peripheral motor pathways.
Muscle hypertrophy affecting the scapular muscles.
Muscle hypertrophy affecting the paraspinal muscles.
Muscle hypertrophy affecting the muscles of the neck.
Hypertrophy of one or more muscles innervated by the facial nerve (the seventh cranial nerve).
Hair on the neck extends less inferiorly than usual.
An anomaly of the neck of the uterus (lower part of the uterus), called the uterine cervix.
An anomaly of the labia minora, the folds of skin between the outer labia.
A structural anomaly of the secretory duct of the testicle that carries spermatozoa from the epididymis to the prostatic urethra where it terminates to form ejaculatory duct.
Spermatozoa with very small cranial ends devoid of any nuclear material, that is, lacking a typical sperm head.
A structural abnormality of the sperm tail.
A structural abnormality of the sperm mid-piece.
A structural abnormality of the sperm neck.
A structural abnormality of the sperm head.
A structural anomaly of a male reproductive cell.
Any structural anomaly of a reproductive cell.
Decreased number or density of the folded ridges (wrinkles) of skin of the scrotum.
Increased number or density of the folded ridges (wrinkles) of skin of the scrotum.
Anomaly of the folded ridges (wrinkles) of skin of the scrotum.
Hypospadias with location of the urethral meatus in the middle of the inferior shaft of the penis.
Hepatic fibrosis that reaches from a portal area to another portal area.
Presence of a unitary trichilemmoma, a benign tumour originating from the outer root sheath of the hair follicle.
Noncompaction cardiomyopathy that affects both ventricles.
A predominantly right ventricular variant of isolated noncompaction cardiomyopathy.
Underdevelopment of part or all of the female external reproductive organs (which include the mons pubis, labia majora, labia minora, Bartholin glands, and clitoris).
Underdevelopment of the breast on both sides.
Decreased distance between the attachments of the alae nasi to the face.
An anomaly of the nasal base, which can be conceived of as an imaginary line between the most lateral points of the external inferior attachments of the alae nasi to the face.
One-sided weakness of the muscles of facial expression and eye closure.
Multiple areas of darker than expected signal on magnetic resonance imaging emanating from the cerebral white matter that surrounds the cerebral ventricles.
A lack of bone mineralization of one or more body of thoracic vertebra.
An anomaly of the process of formation of bone in the humerus.
A type of hearing impairment affecting primarily the middle frequencies of sound (1000 Hz to 3000 Hz).
Hearing loss that occurs acutely and resolves completely.
A glial tumor of the retinal nerve fiber layer arising from a retinal astrocyte.
A structural anomaly of the ciliary body.
A lacy pattern or iris pigmentation that resembles the spokes of a bicycle wheel.
A deviation from normal of the relation between the upper and the lower segment of the body, where the lower segment is defined as the length between the top of pubic symphysis to floor, and the upper segment is defined as the top of head to top of pubic symphysis.
Increased length of the arm span (length from one end of an individual's arms (measured at the fingertips) to the other when raised parallel to the ground at shoulder height at a one-hundred eighty degree angle.
Decreased length of the arm span (length from one end of an individual's arms (measured at the fingertips) to the other when raised parallel to the ground at shoulder height at a one-hundred eighty degree angle.
A deviation from normal of the length of the arm span (length from one end of an individual's arms (measured at the fingertips) to the other when raised parallel to the ground at shoulder height at a one-hundred eighty degree angle.
A deviation from normal size of the placenta.
An increase in size of the anatomic space between the arachnoid membrane and pia mater in the region surrounding the cerebrum.
An increase in size of the anatomic space between the arachnoid membrane and pia mater in the region surrounding the cerebellum.
The presence of atrophy (wasting) of the cerebral white matter.
A reduced ability to participate in the back and forth flow of social interaction, which is normally characterized by an influence of the behavior of one person on the behavior of another person who is in conversation with the first.
A deviation from normal of the neurological development of a child, which may include any or all of the aspects of the development of personal, social, gross or fine motor, and cognitive abilities.
An increased polymorphonuclear cell count in the cerebrospinal fluid.
Abnormal increase in size of the brainstem.
Increased amount of myelin in the central nervous system.
A darker than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a diffuse hypointensity affecting all of the basal ganglia.
A darker than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hypointensity affecting a particular region of the basal ganglia.
A deviation from normal signal on magnetic resonance imaging (MRI) of the basal ganglia.
A darker than expected T2 signal on magnetic resonance imaging (MIR) of the brainstem. This term refers to a diffuse hypointensity affecting the entire brainstem.
A darker than expected T2 signal on magnetic resonance imaging (MIR) of the brainstem. This term refers to a localized hypointensity affecting a particular region of the brainstem.
A lighter than expected T2 signal on magnetic resonance imaging (MIR) of the brainstem. This term refers to a localized hyperintensity affecting a particular region of the brainstem.
A deviation from normal signal on magnetic resonance imaging (MIR) of the brainstem.
Fingernail that appears thin when viewed on end.
Abnormal anatomic location of the anterior pituitary gland.
An eccentric abnormal localized widening (dilatation) of the descending thoracic aorta that involves only a portion of the circumference of the vessel wall
A concentric abnormal localized widening (dilatation) of the descending thoracic aorta that involves the full circumference of the vessel wall
An abnormally decreased potassium concentration in the blood occurring periodically with a return to normal between the episodes.
Abnormal functionality of the gastrointestinal tract.
A profound (essentially complete) form of hearing impairment.
The presence of a moderate form of hearing impairment.
The presence of a mild form of hearing impairment.
A delay in the process of formation and maturation of the epiphysis of one or more vertebrae. [HPO:probinson]
A deviation from normal in the ratio of choline to creatine in the brain identified by magnetic resonance spectroscopy (MRS).
A decrease in the level of N-acetyl aspartate in the brain identified by magnetic resonance spectroscopy (MRS).
An increase in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS).
An increase in the level of choline-containing compounds in the brain identified by magnetic resonance spectroscopy (MRS).
An anomaly of metabolism in the brain identified by magnetic resonance spectroscopy (MRS).
Abnormality in the space in the meninges beneath the arachnoid membrane and above the pia mater that contains the cerebrospinal fluid.
A functional anomaly of the large intestine.
A structural abnormality of a diaphysis of the leg.
Focal proliferation of glial cells in the cerebellum.
A deviation from normal signal on magnetic resonance imaging (MRI) of the thalamus.
A reduction in the quantity of space occupied by the thalamus.
An increase in the quantity of space occupied by the thalamus.
Deviation from the normal range of size of the thalamus.
A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the thalamus. This term refers to a localized hyperintensity affecting a particular region of the thalamus.
A darker than expected T2 signal on magnetic resonance imaging (MRI) of the thalamus. This term refers to a localized hypointensity affecting a particular region of the thalamus.
A darker than expected T2 signal on magnetic resonance imaging (MRI) of the thalamus. This term refers to a diffuse hypointensity affecting the entire thalamus.
An anomaly in the amount or timing of melatonin secretion by the pineal gland. Note that melatonin is also synthesized by multiple tissues outside of the pineal gland.
A functional abnormality of the pineal gland.
An abnormal elevation in the quantity of three-dimensional space taken up by the pineal gland.
An abnormal reduction in the quantity of three-dimensional space taken up by the pineal gland.
An abnormal increase or decrease in the quantity of three-dimensional space taken up by the pineal gland.
A structural abnormality of the pineal gland.
An anomaly of the pineal gland,a small endocrine gland in the brain that produces melatonin.
An increase in the distance between vertebral pedicles, which are the two short, thick processes, which project backward, one on either side, from the upper part of the vertebral body, at the junction of its posterior and lateral surfaces.
An anomalous build up of iron (Fe) in the substantia nigra.
An abnormal build up of iron (Fe) in the globus pallidus.
An anomalous build up of copper (Cu) in the brain.
A failure to develop of the upper vagina.
An abnormal motion of a segment of the left ventricle during the cardiac cycle.
A large reduction in the fraction of blood pumped from the left ventricle with each cardiac cycle. The normal range in adults is at least 55 percent, and a moderate reduction is defined as less than 30 percent.
A medium reduction in the fraction of blood pumped from the left ventricle with each cardiac cycle. The normal range in adults is at least 55 percent, and a moderate reduction is defined as 30-44 percent.
A diminution of the volumetric fraction of blood pumped out of the ventricle with each cardiac cycle.
A small reduction in the fraction of blood pumped from the left ventricle with each cardiac cycle. The normal range in adults is at least 55 percent, and a mild reduction is defined as 45-54 percent.
Reduced uptake of [18F]-fluorodeoxyglucose (FDG) in the parietal cortex as measured by positron emission tomography (PET) brain scan.
Reduced uptake of [18F]-fluorodeoxyglucose (FDG) in the hypothalamus as measured by positron emission tomography (PET) brain scan.
Reduced uptake of [18F]-fluorodeoxyglucose (FDG) in the thalamus as measured by positron emission tomography (PET) brain scan.
Reduced uptake of [18F]-fluorodeoxyglucose (FDG) in the prefrontal cortex as measured by positron emission tomography (PET) brain scan.
An anomaly detectable in [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) brain scans. Glucose uptake measured with FDG-PET is a marker of neuronal metabolic activity.
A functional brain anomaly detectable by positron emission tomography (PET). PET scanning is a method for functional brain imaging, and its measurements reflect the amount of brain activity in the various regions of the brain.
Decreased concentration of dopamine in the cerebrospinal fluid (CSF).
Increased concentration of dopamine in the cerebrospinal fluid (CSF).
Abnormal concentration of dopamine in the cerebrospinal fluid (CSF).
A abnormal increase in the inflammatory response to injury or infection.
An abnormal reduction in the inflammatory response to injury or infection.
Any anomaly of the inflammatory response, a response to injury or infection characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
An elevated concentration of lactate in the caudate nucleus. This finding can be elicited by magnetic resonance spectroscopy imaging.
Decreased amount of pigmentation in the fovea centralis.
A deviation from the norm of the intracranial pressure.
A structural anomaly of the nervous system.
A functional anomaly of the nervous system.
Reduction in the amount of blood flow to the iris.
Shedding of the pigment granules that normally adhere to the back of the iris into the aqueous humor.
An anomaly of the trabecular meshwork, which is the porelike structure surrounding the entire circumference of the anterior chamber at the base of the cornea and near the ciliary body. The trabecular mesh work is responsible for draining the aqueous humor into the canal of Schlemm.
Deposition of fibrillar material that can be found on all anterior segment structures bathed by aqueous humor.
A developmental anomaly associated with the failure of rectum, vagina, and bladder to separate.
Presence of a many diverticula (sac or pouch) in the wall of the urinary bladder.
Presence of erythrocyte casts (cylindrical structures produced by the kidney in certain disease states) in the urine.
Elevated concentration of SO4(2-), i.e., sulfate, in the urine.
Abnormal concentration of sulfate in the urine.
Abnormal concentration of urate in the urine.
An abnormal concentration of magnesium the urine.
An abnormally decreased sodium concentration in the urine.
An abnormal concentration of sodium in the urine.
High urine chloride in the presence of hypochloridemia.
An abnormal concentration of chloride in the urine.
An abnormal phosphate concentration in the urine.
An abnormal concentration of potassium(1+) in the urine.
Severely increased levels of protein in the urine (1000-3000 mg per day in adults).
Moderately increased levels of protein in the urine (500-1000 mg per day in adults).
Mildly increased levels of protein in the urine (150-500 mg per day in adults).
A form of nephrotic syndrome that does not respond to any immunosuppresive treatment.
A two-sided form of atrophy of the kidney.
The presence of complement 3 deposits in the glomerulus.
A type of proximal renal tubulopathy characterized by resorption defects leading to glycosuria, aminoaciduria, tubular proteinuria, renal hypophosphatemia, and urate tubular hyporeabsorption with bicarbonate loss and resulting acidosis.
Stop of growth at the epiphyseal plate the hyaline cartilage plate in the metaphysis at one or more long bones in the ulna, at an earlier than normal age, resulting in growth arrest and shortening of the involved bone.
Stop of growth at the epiphyseal plate the hyaline cartilage plate in the metaphysis at one or more long bones in the radius, at an earlier than normal age, resulting in growth arrest and shortening of the involved bone.
Stop of growth at the epiphyseal plate the hyaline cartilage plate in the metaphysis at one or more long bones in the tibia, at an earlier than normal age, resulting in growth arrest and shortening of the involved bone.
Stop of growth at the epiphyseal plate the hyaline cartilage plate in the metaphysis at one or more long bones in the foot, at an earlier than normal age, resulting in growth arrest and shortening of the involved bone.
Stop of growth at the epiphyseal plate the hyaline cartilage plate in the metaphysis at one or more long bones in the hand, at an earlier than normal age, resulting in growth arrest and shortening of the involved bone.
A ratio of serum triiodothyronine (T3) to thyroxine (T4) in the blood that is lower than normal.
A ratio of serum triiodothyronine (T3) to thyroxine (T4) in the blood that is higher than normal.
A ratio of serum triiodothyronine (T3) to thyroxine (T4) in the blood that deviates from normal.
EEG with focal sharp transient waves in the centrotemporal region of the brain (also known as the central sulcus), i.e., focal sharp waves of a duration less than 80 msec followed by a slow wave.
A thumbnail that is diminished in length and width, i.e., underdeveloped thumb nail.
Presence of an elevanted number of projections from nuclei of neutrophils. Ths projections can have the shape of hooks, tags, or clubs. [HPO:probinson]
Lack of specific granules in neutrophils.
The presence of varices (enlarged and convoluted blood vessels) in the colon.
A lipoma (a benign tumor composed of adipose tissue) located in the conjunctiva.
Anomalous movements of the eyes that occur without the subject wanting them to happen.
A deviation from equal (50%) inactivation of each parental X chromosome in maternal cells.
An decreased concentration of fructose 1,6-bisphosphate aldolase in the serum.
An increased concentration of fructose 1,6-bisphosphate aldolase in the serum.
The presence of circulating autoantibodies to anticardiolipin in the mother.
A deviation from the normal count of dense granules per thrombocyte.
A deviation from the normal count of alpha granules per thrombocyte.
A deviation from the normal contents of the platelet alpha granules, which normally contain hemostatic proteins such as fibrinogen, von Willebrand factor, and growth factors such as platelet-derived growth factor.
A lack of platelet alpha granules. This typically results in the grey appearance of platelets in giemsa stained blood smears.
An anomalous location and arrangement of platelet alpha granules.
A deviation from the normal discoid platelet shape.
A form of telangiectasis characterized by a central elevated red dot the size of a pinhead, representing an arteriole, with numerous small blood vessels that radiate out thereby resembling the legs of a spider. Characteristically, compression of the central arteriole causes the entire lesion to blanch, and the lesion quickly refills once the compression is released.
An anomaly of the circle of Willis, also known as the cerebral arterial circle.
An abnormally decreased amount of catalase activity.
A pale yellow discoloration of the entire optic disc.
An increased amount of cerebrospinal fluid (CSF) in the subarachnoid space.
An abnormally decreased amount of thyroxin-binding globulin (TBG) in blood. TBG is responsible for carrying the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in the bloodstream.
An abnormally decreased size of the pituitary gland.
A deviation from the normal size of the pituitary gland.
An anomaly of the internal capsule, which is an area of white matter in the brain that separates the caudate nucleus and the thalamus from the putamen and the globus pallidus.
An anomaly of the white matter of brainstem.
A wartlike (with multiple small elevated projections) papule.
A separation of the layers within the wall of the descending aorta. Tears in the intimal layer result in the propagation of dissection (proximally or distally) secondary to blood entering the intima-media space.
A decrease in the maximum amount of pressure of expired air achieved by a person after a full inspiration.
A decrease in the maximum amount of negative pressure a person can generate during an inhalation.
An anomaly of the intracellular membrane complexes known as the dense tubular system.
An arachnoid cyst that progressively enlarges from an abnormality in the membrane of Liliequist or in the interpeduncular cistern, and typically, expands from the prepontine space, displacing the floor of the third ventricle upwards, the pituitary stalk and optic chiasm upwards and forwards, and the mammillary bodies upwards and backwards.
An arachnoid cyst located within the ventricular system.
An arachnoid cyst located at the margin of the cerebellum and pons.
Defective structure, size or content of dense granules, platelet organelles that contain granules proaggregatory factors such as adenosine diphosphate (ADP), adenosine triphosphate (ATP), ionized calcium , histamine and serotonin.
Defective structure, size or content of alpha granules, platelet organelles that contain several growth factors destined for release during platelet activation at sites of vessel wall injury.
A venous angioma of the frontal lobe of the brain.
A wavering, unsteady voice that reflects involuntary and approximately sinusoidal oscillation of motor unit firings of laryngeal muscles. Vocal tremor results in low frequency modulations of voice frequency or amplitude and intermittent voice instability.
The presence of normal overall immunoglobulin levels with deficiency of specific immunoglobulins directed against pneumococci.
An increased level of iron in liver tissues.
An above normal level of saturation of serum transferrin with iron.
A structural anomaly of the inferior portion of the vermis of cerebellum.
Calcification, that is, pathological deposition of calcium salts in the tunica media of small arteries.
Calcification, that is, pathological deposition of calcium salts in the tunica media of medium-sized (muscular or distributive) arteries.
Calcification, that is, pathological deposition of calcium salts in the tunica media of arteries.
A chronic loss of wrist joint motion on one side only. [HPO:probinson]
A chronic loss of wrist joint motion on the right and left sides.
Inflammation of the synovial membrane of the sacroiliac joint.
A reduced concentration of 5-methyltetrahydrofolate(2-) in the cerebrospinal fluid (CSF). 5-methyltetrahydrofolate is the active folate metabolite.
A functional abnormality of the biliary tree.
A functional anomaly of the gallbladder.
A structural anomaly of the gallbladder.
Reduction in length of the ventral (lower) skin of prepuce of penis.
A failure to meet one or more age-related milestones of social behavior.
Intermittent and recurrent bouts of a subjective feeling of tiredness characterized by a lack of energy and motivation.
Underdevelopment of the cerebral white matter.
An increased degree of femoral version, which is defined as the angular difference between axis of femoral neck and transcondylar axis of the knee. Thus, femoral anteversion is an inward twisting of the femur that causes the knees and feet to turn inward.
An abnormally high level of blood oxygen.
Wasting or decrease in size of all or part of the duodenum.
The presence of a V-shaped indentation (notch) in the primary central incisor. [HPO:probinson]
A deviation from normal of the concentration of citrate(3-) in the urine.
A lower than normal concentration of 2-oxoglutaric acid in the urine.
A greater than normal concentration of 2-oxoglutaric acid in the urine.
An abnormal concentration of aldolase in the serum. Aldolase is an enzyme responsible for converting fructose 1,6-bisphosphate into the triose phosphates dihydroxyacetone phosphate and glyceraldehyde 3-phosphate.
Allergy to iodine contrast media used in radiological studies.
Reduced intensity of muscle tendon reflexes in jaw.
Muscular hypotonia of one or more limbs.
A delay in the development of skills required to feed oneself in the toddler period (between one and three years of age).
Reduced carnitine O-palmitoyltransferase activity, i.e., reduced activity of the reaction: palmitoyl-CoA + L-carnitine = CoA + L-palmitoylcarnitine.
An altered ability of any enzyme or their cofactors to act as catalysts. This term includes changes due to altered levels of an enzyme.
An abnormality of the malar surface of the zygomatic bone and including the frontal process of maxilla.
Bony defects situated along the cranial suture lines or at the junction of the bone plates of the skull.
An reduced addition of sialic acids to O-linked glycans.
An anomaly of the addition of sialic acids to O-linked glycans.
Increased addition of fucose sugar units to O-linked glycans.
A reduction of the addition of fucose sugar units to O-linked glycans.
An anomaly of the addition of fucose sugar units to O-linked glycans.
An anomaly of protein O-linked glycosylation, i.e., of the process in which a carbohydrate or carbohydrate derivative unit is added to a protein via the hydroxyl group of a serine or threonine residue.
Increased addition of mannose to N-linked glycans.
Reduced addition of mannose to N-linked glycans.
An anomaly of the addition of mannose to N-linked glycans.
Increased addition of fucose sugar units to N-linked glycans.
Decreased addition of fucose sugar units to N-linked glycans.
An anomaly of the addition of fucose sugar units to N-linked glycans.
Increased addition of sialic acids to N-linked glycans.
Decreased addition of sialic acids to N-linked glycans.
An anomaly of the addition of sialic acids to N-linked glycans.
A reduction in the amount of galactose residues of N-glycans.
An anomaly of protein N-linked glycosylation, i.e., an abnormality of the protein glycosylation process in which a carbohydrate or carbohydrate derivative unit is added to a protein via a nitrogen atom in an amino acid residue in a protein.
An anomaly of a protein glycosylation process, i.e., of a protein modification process that results in the addition of a carbohydrate or carbohydrate derivative unit to a protein amino acid, e.g. the addition of glycan chains to proteins.
An anomaly of a glycosylation process, i.e., a process involved in the covalent attachment of a glycosyl residue to a substrate molecule.
An reduction in the number of calories used per unit time.
An increase in the number of calories used per unit time.
Any anomaly in the utilization of energy (calories).
An anomaly in the processes involved in the maintenance of an internal equilibrium.
An abnormality of the metabolism of folic acid, which is also known as vitamin B9.
A functional abnormality of the autonomic nervous system.
A structural abnormality of the autonomic nervous system.
Lack of skin pigmentation (coloring) of the arms and legs.
Lack of skin pigmentation (coloring) of the abdomen.
An anomaly of the process of rib bone formation.
Narrowing or constriction of the aorta localized to the region of the descending trunk of arch of aorta.
Failure of the ureter to undergo development.
Increased length of the middle phalanx of finger.
Reduced diameter of the proximal phalanx of finger.
Reduced diameter of the distal phalanx of finger.
Reduced diameter of the middle phalanx of finger.
Abnormality of the occipital bone of the skull.
An abnormal pigmentation pattern of the external genitalia.
A congenital defect with an abnormal joining of the gums of the upper and lower jaw.
Decreased secretion of luteinizing hormone-releasing hormone by the hypothalamus.
An abnormal functionality of the hypothalamus.
Reduced size of the proximal epiphysis of the tibia.
Reduced size of the Distal epiphysis of femur.
Reduced concentration of serine in the blood.
An abnormally reduced concentration of glycine in the blood.
A type of autosomal dominant inheritance involving a gene that is imprinted with paternal silencing.
An increase in the combined thickness of the intima and media of the carotid artery.
Intermittent episodes of increased resistance to the passage of air in the upper airway.
A decreased amount of glycogen in muscle tissue.
Any anomaly in the amount of glycogen in muscle tissue.
Absence of the radial spokes of the axoneme of the respiratory cilium.
Absence of the two central microtubules of motile cilia with a 9+2 microtubuluar configuration.
Any anomaly of the normal motility of motile cilia. Evaluation of ciliary beat frequency and ciliary beat pattern requires high-speed videomicroscopy of freshly obtained ciliary biopsies that are maintained in culture media under controlled conditions.
Any functional anomaly of the respiratory motile cilia.
A structural anomaly of the two central microtubules of motile cilia with a 9+2 microtubuluar configuration.
Complete absence of the dynein arms of respiratory motile cilia, that is, absence of the inner and the outer dynein arms, which normally are situated inside and outside of the peripheral microtubules of motile cilia. This feature is usually appreciated by electron microscopy.
Abnormal arrangement of the structures of the axoneme, which is the cytoskeletal structure that forms the inner core of the motile cilium and displays a canonical 9 + 2 microtubular pattern of motile cilia studded with dynein arms.
Absence of the outer dynein arms of respiratory motile cilia, which normally are situated within the peripheral microtubules of motile cilia. This feature is usually appreciated by electron microscopy.
Absence of the outer dynein arms of respiratory motile cilia, which normally are situated outside of the peripheral microtubules of motile cilia. This feature is usually appreciated by electron microscopy.
An anomaly of the dynein arms of motile cilia. This feature is usually appreciated by electron microscopy.
Any structural anomaly of the pseudostratified ciliated epithelium that lines much of the conducting portion of the airway, including part of the nasal cavity and larynx, the trachea, and bronchi.
A structural anomaly of the respiratory system.
An electrocardiographic anomaly of the ST segment, which is the segment that connects the QRS complex and the T wave. The ST segment normally has a duration of 80 to 120 ms, is flat and at the same level (isoelectric) as the PR and TP segment.
Development of the reproductive system is inconsistent with the chromosomal sex.
Anomaly of primary or secondary sexual development or characteristics.
The presence of multiple hemangiomas in the arachnoid.
The presence of multiple epithelioid cell granulomas consist of highly differentiated mononuclear phagocytes (epithelioid cells and giant cells) and lymphocytes, not exhibiting caseation (a form of necrosis in which the tissue changes into a dry, amorphous mass said to resemble cheese).
Increased concentration of porphobilinogen in the urine.
Recurrent infection involving the vulva, vagina, and adjacent crural areas, whereby the causative agent belongs to the genus Candida.
An increase in the concentration of bile acid in the blood.
An anomaly of clotting factor II, which is known as prothrombin, a vitamin K-dependent proenzyme that functions in the blood coagulation cascade.
The presence of more than 5 juvenile polyps of the colon. The term juvenile polyps refer to a special histopathology and not the age of onset as the polyp might be diagnosed at all ages. The juvenile polyp has a spherical appearance and is microscopically characterized by overgrowth of an oedematous lamina propria with inflammatory cells and cystic glands.
An increased concentration of protoporphyrins in erythrocytes.
An entrapment neuropathy of the ulnar nerve in the cubital tunnel (in the elbow) characterized by numbness in the ring and little fingers and weakness of the intrinsic muscles in the hand.
Injury to the median nerve caused by its entrapment at the wrist as it traverses through the carpal tunnel. Clinically, constrictive median neuropathy is characterized by pain, paresthesia, and weakness in the median nerve distribution of the hand.
Presence of multiple hyperplastic polyps in the colon. Hyperplastic polyps are generally about 5 mm in size and show hyperplastic mucosal proliferation.
A form of focal dystonia affecting the face and especially the jaw that is induced by the act of speaking. It is an involuntary contraction of the masticatory muscles, resulting in dysarthria or dysphagia. [HPO:probinson]
A functional anomaly of the natural killer cell.
Habitual repetitive movement of the body.
Habitual clasping and squeeezing of the hands.
A separation (dissection) of the layers of the common carotid artery wall.
A separation (dissection) of the layers of the external carotid artery wall.
A separation (dissection) of the layers of the intracranial portion of the internal carotid artery wall.
Atrophy of the cerebral subcortical white and gray matter, termed subcortical atrophy, reflects loss of nerve cells in the basal ganglia or fibers in the deep white matter.
Abnormality/dysplasia of a single myeloid cell (erythroid, granulocytic, or megakaryocytic).
Myelodysplasia with dysplastic changes in two of the myeloid lineages: erythroid, granulocytic, megakaryocytic.
Myelodysplasia with dysplastic changes in two or more of the myeloid lineages: erythroid, granulocytic, megakaryocytic.
Decreased quantity of von Willebrand factor.
Decreased quantity or activity of von Willebrand factor. Von Willebrand factor mediates the adhesion of platelets to the collagen exposed on endothelial cell surfaces.
Any structural anomaly of a myeloid mononuclear recirculating leukocyte that can act as a precursor of tissue macrophages, osteoclasts and some populations of tissue dendritic cells.
Any structural anomaly of megakaryocytes. Mature blood platelets are released from the cytoplasm of megakaryocytes, which are bone-marrow resident cells.
An anomaly of cells involved in the formation of a granulocytes, that is, of the granulocytopoietic cell.
A deviation from the normal count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.
Deviation from normal concentration of albumin in the blood.
An abnormality of the concentration of corticosterone in the blood.
An abnormality of the concentration of a glucocorticoid in the blood.
Disproportionate shortening of the proximal segment of the leg (i.e. the femur).
An anomaly of the mitochondrion, the membranous cytoplasmic organelle the interior of which is subdivided by cristae. The mitochondrion is a self replicating organelle that is the site of tissue respiration.
A deviation from the normal number of mitochondria per cell.
A congenital inclusion cysts that arises from the inclusion of ectodermally committed cells at the time of neural tube closure (3rd-5th week of embryogenesis). The capsule of dermoid cysts consists of simple epithelium supported by collagen. In thicker parts, the lining is supplemented with dermis containing hair follicles, sebaceous glands, and apocrine glands.
A congenital inclusion cysts that arises from ectodermal cells that normally form skin cells being left behind in the nervous system during development.
A deviation from the normal size of the pancreas.
A function abnormality of the endocrine pancreas.
An anomaly of the function of the pancreas.
An anomaly in the surface contour of mitochondria.
Any abnormality of the size of the skeletal muscle cell.
Atrophy of the cerebellum affecting primarily the Purkinje cell layer.
Atrophy of the cerebellum affecting primarily the granular cell layer.
Any anomaly of the conduction of motor nerve impulses in the central nervous system.
Blockade of impulses at a focal site along the course of a motor axon.
Ab abnormal distribution of N-acylglycines (CHEBI:16180) in the urine. There are numerous different N-acylglycines, and this term refers to pathological alterations in their level or distribution.
An abnormality of acylcarnitine, which is produced by reversible esterification of the 3-hydroxyl group of carnitine.
An increased concentration of chondroitin sulfate (CHEBI:37397) in the urine.
Increased excretion of glycopeptides in the urine. Glycopeptides are peptides with carbohydrate moieties covalently attached to the side chains of the amino acid residues.
Increased concentration of disaccharide in the urine.
Presence of multiple cystic changes in multiple ares or multiple bones.
A reduced concentration of calcifediol in the blood. Calcifediol is also known as calcidiol, 25-hydroxycholecalciferol and 25-Hydroxyvitamin D3.
A reduced concentration of calcitriol in the blood. Calcitriol is also known as 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3.
Wasting of the pectoral muscles, i.e., of the pectoralis major and pectoralis minor.
Wasting of the sternocleidomastoid muscle, the muscle in the anterior part of the neck that acts to flex and rotate the head.
Abnormally increased concentration of cortisol in the urine.
An abnormal concentration of a hormone in the urine.
Abnormality of a metabolism or concentration of ornithine.
Elevated concentration of galactose in the blood.
Persistence of blood flow through the ductus venosus for longer than the normal time after birth.
EEG with focal sharp transient waves of a duration less than 80 msec in the temporal region.
EEG with focal sharp transient waves of a duration less than 80 msec in the parietal region.
EEG with focal sharp transient waves of a duration less than 80 msec in the occipital region.
EEG with focal sharp transient waves of a duration less than 80 msec in the frontal region.
EEG with focal sharp transient waves of a duration less than 80 msec in the central region.
EEG with focal sharp transient waves in the parietal region, i.e., focal sharp waves of a duration less than 80 msec followed by a slow wave. [HPO:jalbers]
EEG with focal sharp transient waves in the parietal region, i.e., focal sharp waves of a duration less than 80 msec followed by a slow wave.
EEG with focal sharp transient waves in the occipital region, i.e., focal sharp waves of a duration less than 80 msec followed by a slow wave.
EEG with focal sharp transient waves in the frontal region, i.e., focal sharp waves of a duration less than 80 msec followed by a slow wave.
EEG with focal sharp transient waves in the central region, i.e., focal sharp waves of a duration less than 80 msec followed by a slow wave.
Auras with an alteration of actual percepts involving the visual, auditory, somatosensory, olfactory or gustatory systems.
Auras with creation of composite perceptions without corresponding external stimuli involving visual, auditory, somatosensory, olfactory and/or gustatory phenomena.
Auras which reflect ictal dysmnesia such as: feelings as familiarity (deja-vu) and unfamiliarity (jamais-vu).
Affective auras with subjective qualities similar to those experienced in life but are recognized by the subject as occurring outside of actual context.
Affective, mnemonic or composite perceptual auras with subjective qualities similar to those experienced in life but are recognized by the subject as occurring outside of actual context.
EEG with repetitive generalized sharp transient waves of a duration less than 80 msec.
Abnormally increased level of blood lactate following a meal.
A reduction in the ability of neutrophils to kill bacteria.
An abnormal form or size of neutrophils.
A functional abnormality of neutrophils.
Formation of abnormal bony tissue within ligament tissue.
Formation of abnormal bony tissue within tendon tissue.
Formation of abnormal bony tissue within muscle tissue.
A type of pigment gallstone that is brown, containing calcium fatty acids. These stones are softer than black pigment gallstones.
A type of pigment gallstone that is hard and black, containing calcium carbonate and calcium phosphates.
An increased concentration of dopamine in the urine.
An elevated concentration of luteinizing hormone in the blood.
An increased concentration of citrulline in the blood.
Abnormality of a metabolism or concentration of citrulline.
History of repeated intermittent involuntary muscle contractions that were painful.
Absence of any measurable level of sperm in his semen, due to a hypothalamic or pituitary abnormality diagnosed with hypo-gonadotropic-hypogonadism. The diagnosis is made on the basis of low LH and FSH levels and low or normal testosterone levels.
Absence of any measurable level of sperm in his semen, resulting from post-testicular obstruction or retrograde ejaculation. Can be differentiated from obstructive azoospermia on the basis of testicular biopsy.
Hypoplasia (underdevelopment) of the pectoralis minor on only one side of the chest.
An abnormality of the pectoral muscle, comprising the pectoralis major, a thick, fan-shaped muscle of the anterior chest and the pectoralis minor, a thin, triangular muscle situated underneath the pectoralis major.
A lymphoproliferative abnormality of the intestine characterized by numerous visible mucosal nodules measuring up to, and rarely exceeding, 0.5 cm in diameter Histologically, hyperplastic lymphoid follicles with large germinal centres are seen in the lamina propria and superficial submucosa. There is enlargement of the mucosal B cell follicles caused by hyperplasia of the follicle centres; surrounded by a normal appearing mantle zone. Disease may involve the stomach, the entire small intestine, and the large intestine.
The presence of multiple granulomas in the liver as based on pathological examination. Granulomas are small 0.5 to 2 mm collections of modified macrophages called epithelioid cells usually surrounded by lymphocytes.
An acute episode of pneumonia due to the aspiration (breathing in) of food, liquid, or gastric contents into the upper respiratory tract.
Acute inflammation of the lung due to an infection.
A type of vasculitis (inflammation of blood vessel walls) that affects blood vessels that are smaller than arteries, i.e., arterioles, venules, and capilllaries.
An abnormality of the shape of the lumbar vertebra L2 such that it is wedge-shaped (narrow towards the front).
A soft tissue continuity in the A/P axis between fingers 4 and 4.
A decreased concentration of total carnitine in the blood.
Decreased concentration of urate in the urine.
Abnormal outpouching or sac-like dilatation in the wall of the inferior mesenteric artery or superior mesenteric artery .
An anomaly of the superior cerebellar peduncle.
An anomaly of the cerebellar peduncles. The superior, middle, and inferior cerebellar peduncles emerge from the cerebellum. The superior cerebellar penduncles connect the cerebellum to the midbrain, the middle cerebellar peduncles connect the cerebellum to the pons, and the inferior cerebellar peduncle connects the medulla spinalis and medulla oblongata with the cerebellum.
Presence of an additional phalanx-like bone, producing an extra, wedge-shaped bone at the base of the proximal phalanx of the third finger.
Developmental hypoplasia (shortening) of proximal phalanx of toe.
One or more digit that appears disproportionately short compared to the hand/foot, whereby either the entire digit or a specific phalanx is shortened.
A reduction in the activity of the mitochondrial proton-transporting ATP synthase complex, which makes ATP via oxidative phosphorylation, and is sometimes described as Complex V of the electron transport chain. [HPO:probinson]
An increased or decreased activity of the mitochondrial respiratory chain.
Atrophy of the extensor digitorum longus muscles, which mediate extension of the toes.
Abnormal calcification in the cardiovascular system.
Excessive, increased hair growth located in the thoracic region.
Excessive, increased hair growth located in the lumbar region.
An anomaly of the glenoid fossa, also known as the glenoid cavity, which is the articular surface of the scapula that articulates with the head of the humerus.
An anomaly of a metacarpophalangeal joint.
Abnormal reduction in length affecting all phalanges.
Abnormally flat shape of the heads of the metacarpal bones.
Missing radius bone on one side only associated with congenital failure of development.
A reduction in the ratio of production of alpha globin to that of beta globin. This is the major abnormality in the various forms of alpha thalassemia.
A reduction in the ratio of production of beta globin to that of alpha globin. This is the major abnormality in the various forms of beta thalassemia.
Hemoglobin A (HbA) contains two globin alpha chains and two globin beta chains. HbA is normally the main adult hemoglobin, representing about 96-98 percent of all hemoglobin. This term represents a decreased in the proportion of HbA below this limit, and can be seen in various forms of thalassemia.
An abnormality of the level of activity of circulating fibrinogen.
Abnormal response to thromboxane as manifested by reduced or lacking aggregation of platelets upon addition of thromboxane A2 receptor agonists.
Prolonged or protracted bleeding following an invasive procedure or intervention.
Significant bleeding or hemorrhage without significant precipitating factor.
Bleeding sufficiently severe as to require red cell transfusion (WHO Grade 3 or 4).
Abnormal bleeding of the umbilical stump following separation of the cord at approximately 7-10 days after birth.
An anomaly of alpha or dense granules or platelet lysosomes.
Decreased cell membrane concentration of P2Y12 receptor.
Decreased cell membrane concentration of glycoprotein VI.
An acute form of disseminated intravascular coagulation. Acute DIC can occur following sudden exposure of blood to procoagulants, with the compensatory hemostatic mechanisms becoming overwhelmed.
Decreased cell membrane concentration of the glycoprotein complex Ib-IX-V.
Presence of reduced amount of a membrane protein on the cell membrane of platelets. This feature is typically measured by flow cytometry.
Anomalous size of platelets. Most normal sized platelets are 1.5 to 3 micrometers in diameter. Large platelets are 4 to 7 micrometers. Giant platelets are larger than 7 micrometers and usually 10 to 20 micrometers.
Abnormal response to thrombin or thrombin mimetics as manifested by reduced or lacking aggregation of platelets upon addition of thrombin (or thrombin mimetics).
Abnormal response to ristocetin as manifested by reduced or lacking aggregation of platelets upon addition of ristocetin.
Abnormal response to arachidonic acid as manifested by reduced or lacking aggregation of platelets upon addition of arachidonic acid.
An anomaly of the ilium ala. This is the large expanded portion of the ilum which bounds the greater pelvis laterally.
An abnormally increased diphosphate(4-) concentration in the blood. Diphosphate(4-), as ester with two phosphate groups, is also known as pyrophosphate.
Any structural anomaly of the connective tissue bundles in the extracellular matrix of bone tissue that are composed of collagen, and play a role in tissue strength and elasticity.
Decreased activity of coagulation factor IX. Factor IX, which itself is activated by factor Xa or factor VIIa to form factor IXa, activates factor X into factor Xa.
Accumulation of serous fluid (pale yellow and transparent fluid) in the pericardial sac.
Any anomaly in the formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance.
Short (hypoplastic) second metatarsal bone.
An abnormality of the appendicular skeletal system, consisting of the of the limbs, shoulder and pelvic girdles.
An abnormality of the function of the skeletal system.
An abnormality of the form, structure, or size of the skeletal system.
Detectable but decreased IgA levels that are more than 2 standard deviations below normal age-adjusted means.
Delayed maturation and calcification of the talus.
A noninflammatory, progressive occlusion of the intracranial carotid arteries owing to the formation of netlike collateral arteries arising from the circle of Willis.
Horizontal crease or fold situated below the vermilion border of the lower lip and above the fatty pad of the chin, with the face at rest.
Increased width of the midpoint of the mandible (mental protuberance) and overlying soft tissue.
Absence of the normal opening of the choana (the posterior nasal aperture) as a result of an obstructing choanal membrane that may be thin and strandlike or thick and pluglike.
A cleft of the muscular (soft) portion of the palate that is covered by mucous membrane. Soft-palate submucous clefts are characterized by a midline deficiency or lack of muscle tissue.
Basal encephalocele is an encephalocele that occurs along the cribriform plate or through the sphenoid bone. The mass may appear in the nasal cavity, nasopharynx, epipharynx, sphenoid sinus, posterior orbit, or pterygopalatine fossa. The important distinction from other types is that no external tumor is visible except in those rare instances of herniations so large that they protrude through the mouth or nares.
Lipofuscin (age pigment) is a brown-yellow, electron-dense, autofluorescent material that accumulates progressively over time in lysosomes of postmitotic cells, such as neurons and cardiac myocytes. This term pertains if there is an increase in the accumulation of lipofuscin (also known as autofluorescent lipoprotein) more than expected for the age of the patient.
A reduced ability to distinguish tactile sensations at points that are very close to one another. This can be tested by using special calipers whose points can be set from 2mm to several centimeters apart.
A type of myotonia that worsens with repeated muscle contractions.
Atrophy (wasting) affecting primary type 1 muscle fibers. This feature in general can only be observed on muscle biopsy.
A structural abnormality of a skeletal muscle.
A functional abnormality of a skeletal muscle.
The presence of an embryonal neoplasm of the kidney that primarily affects children.
Neoplasm categorized according to the anatomical site of origin of the neoplasm.
Neoplasm categorized according to type of histological abnormality.
Loss-of-function thyroid-stimulating hormone receptor (TSHR) defect.
Gain-of-function thyroid-stimulating hormone receptor (TSHR) defect.
Absence of a lobe of the thyroid gland related to a failure of its embryologic development.
A structural abnormality of the thyroid gland.
An abnormal anatomical location of the parathyroid gland.
Abnormal embryonic development of the parathyroid gland.
A functional abnormality of the parathyroid gland.
A structural abnormality of the parathyroid gland.
A spindled-to-epithelioid, oncocytic, nonendocrine neoplasm of the anterior hypophysis that manifests in adults and follows a benign clinical course. Pituitary spindle cell oncocytomas are firm, fibrous, and adherent to surrounding structures and are highly vascular.
Underdevelopment of the neurohypophysis.
Absence of the neurohypophysis owing to a developmental defect.
An abnormality of the neurohypophysis, which is also known as the posterior lobe of the hypophysis.
A tumor (abnormal growth of tissue) of the adenohypophysis, which is also known as the anterior lobe of the pituitary gland.
An abnormality of the adenohypophysis, which is also known as the anterior lobe of the pituitary gland.
Hypercortisolemia associated with a overproduction of ACTH (often from a tumor), leading secondarily to overproduction of cortisol. [HPO:probinson]
A form of primary hyperaldosteronism in which the overproduction of aldosterone cannot be suppressed by the administration of dexamethasone or similar glucocorticoids. [DDD:spark, HPO:probinson]
A form of primary hyperaldosteronism in which the overproduction of aldosterone can be suppressed by the administration of dexamethasone.
Adrenal insufficiency secondary to a defect in the corticotropin-releasing hormone receptor. [DDD:spark]
Adrenal insufficiency secondary to a defect in ACTH production.
A functional abnormality of the adrenal glands.
Any structural anomaly of the adrenal glands.
An abnormality of the concentration of cortisol in the blood.
An abnormality of cortical sensation. Assuming the primary sensory modalities are intact and the patient is alert and cooperative, the presence of an abnormality of sensory function usually indicates a lesion of a parietal cortex or of the thalamocortical projections to the parietal cortex.
An abnormality in the range and ease of motion of joints across their normal range.
Clonus at the elbow joint, i.e., an exaggerated phasic stretch reflex characterized by repetitive, rhythmic contractions at the elbow, generated by rapid passive stretch at the elbow joint.
Defect or defects of the morphogenesis of the right heart identifiable at birth.
Accessory pathway-related atrioventricular reentrant tachycardia (AVRT) involves an abnormal electrical conduction of the accessory pathway. The accessory pathway connecting impulses between the atrium and the ventricle can be seen at any site in the AV groove.
Libman-Sacks valvular lesions are sterile fibrofibrinous vegetations that favor the left-sided heart valves and usually form on the ventricular surface of the mitral valve.
An abnormality of the sinoatrial (SA) node in the right atrium. THe SA node acts as the pacemaker of the heart.
Supraventricular tachycardia with an accessory connection mediated pathway that is called concealed becasue it is not seen on the ECG during sinus rhythm.
The superior vena cava passes below the aortic arch.
A type of tetralogy of Fallot with pulmonary atresia in which all pulmonary blood flow is derived from major aortopulmonary collateral arteries (MAPCA).
Interrupted inferior vena cava with azygous continuation is the result of connection failure between the right subcardinal vein and the right vitelline vein. Consequently, venous blood from the caudal part of the body reaches the heart via the azygous vein and superior vena cava.
A persistent left superior vena cava (PLSVC) that drains into the left atrium instead of the right atrium via the coronary sinus, resulting in a right to left sided shunt.
A double outlet right ventricle with a ventricular spetal defect (a hole between the two bottom chambers (ventricles) of the heart), that is considered to be closely related to the pulmonary origin. There is not associated pulmonary stenosis, the abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
A double outlet right ventricle with a ventricular spetal defect (a hole between the two bottom chambers (ventricles) of the heart), that is considered to be closely related to the pulmonary origin. There is associated pulmonary stenosis, the abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
A double outlet right ventricle with a ventricular spetal defect (a hole between the two bottom chambers (ventricles) of the heart), that is considered to be closely related to the aortic origin. There is not associated pulmonary stenosis, the abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
A double outlet right ventricle with a ventricular spetal defect (a hole between the two bottom chambers (ventricles) of the heart), that is considered to be closely related to the aortic origin. There is associated pulmonary stenosis, the abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
A double outlet right ventricle with a non-committed ventricular septal defect (VSD), which is a VSD that is anatomically related to, or close to, neither great vessel, being separated from both by considerable muscle, but there is not accompanying pulmonary stenosis; the abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
A double outlet right ventricle with a non-committed ventricular septal defect (VSD), which is a VSD that is anatomically related to, or close to, neither great vessel, being separated from both by considerable muscle, and also has a pulmonary stenosis; abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
A double outlet right ventricle with a subaortic ventritricular septal defect (a hole between the two bottom chambers (ventricles) of the heart), that extends anterosuperiorly and arere closely related to the pulmonary artery as well, are considered to be doubly committed. There is not associated pulmonary stenosis, the abnormal narrowing or constriction of the pulmonary artery, in the main pulmonary artery and/or in the left or right pulmonary artery branches.
Abnormal persistent patency of the ductus arteriosus when birth was at less than 37 weeks completed gestation.
Abnormal persistent patency of the ductus arteriosus in postnatal life when birth was at 37 completed weeks of gestation or greater.
Narrowing or constriction of the aorta localized at the insertion of the ductus arteriosus, i.e., to the juxtaductal region of aortic arch.
The presence of a single coronary artery ostium from which both coronary arteries arise.
A coronary artery begins (branches off from) the pulmonary artery rather than as normal from the root of the aorta.
Isolated abnormalities of the coronary artery origins. This may be in associated with other structural heart malformations but not the patterns of complex structural heart malformations which result in abnormal course of the coronary arteries.
Lack of a part of the pericardium over the diaphragmatic surface of the heart. It is a congenital defect, not the result of a pericardectomy. Pericardium is present on other parts of the heart.
A congenital anomaly with lack of part of the pericardium on the lefthand side of the heart.
A congenital anomaly with complete lack of the pericardium on the lefthand side of the heart.
A congenital anomaly with lack of part of the pericardium on the righthand side of the heart.
No pericardium is present on the righthand side of the heart. It is a congenital absence of pericardium rather than the result of a pericardectomy.
No pericardium over the diaphragmatic surface of the heart. It is a congenital defect, not the result of a pericardectomy. Pericardium is present on other parts of the heart.
A developmental defect of the pericardium with congenital onset.
Aorto-ventricular tunnel is a congenital, extracardiac channel which connects the ascending aorta above the sinutubular junction to the cavity of the left, or (less commonly) right ventricle.
A type of muscular ventricular septal defect characterized by the presence of multiple small defects in the ventricular septum.
A muscular ventricular septal defect located at the apex of the heart.
A type of ventricular septal defect communicating directly between the left ventricle and right atrium. This is anatomically possible because the normal tricuspid valve is more apically displaced than the mitral valve.
An abnormality of the abdominal situs, i.e., of the sidedness of the abdomen and its organs.
An abnormality of the pulmonary situs, i.e., of the sidedness of the morphological right and left lungs, in which both lungs have the morphology of a left lung.
An abnormality of the pulmonary situs, i.e., of the sidedness of the morphological right and left lungs, in which both lungs have the morphology of a right lungs.
An abnormality of the pulmonary situs, i.e., of the sidedness of the morphological right and left lungs, in which the morphology of both left and right lungs is the same.
Mirror image arrangement of the mainstem bronchi with the right pulmonary artery posterior to the right upper lobe bronchus and the left pulmonary artery anterior to the left upper lobe bronchus.
An abnormality of the pulmonary situs, i.e., of the sidedness of the morphological right and left lungs, which is defined by characteristics such as the number of lobes per lung and the relationship of the pulmonary arteries to their bronchi.
A congenitally corrected transposition of the great arteries with a ventricular septal defect: a hole between the two bottom chambers (ventricles) of the heart. The ventricular septal defect is centered around the most superior aspect of the ventricular septum.
Abnormal plane of direction of the heart from the base to the apex in the midline. Left sided is normal.
Abnormal plane of direction of the heart from the base to the apex towards the right. Left sided is normal.
Abnormal plane of direction of the heart from the base to the apex. Left sided is normal.
The ring may be completed by the ductal ligament.
Aortic arch crosses the left mainstem bronchus. The first branch is the right carotid artery, the second branch is the left carotid artery, the third branch is the subclavian artery, the fourth branch is the right subclavian artery arising from the posteromedial aspect of the distal aortic arch and continuing posterior to the esophagus to the right hand side of the body.
Aortic arch crosses the right mainstem bronchus. The left carotid artery is the first branch, right carotid artery the second branch and right subclavian artery as the third branch.
The subclavian artery arises from ductus arteriosus. While the ductus arteriosus is patent its blood supply comes from the ductus, hence from the pulmonary artery. After it closes, the blood supply is retrogradely from the vertebral artery via the circle of Willis.
A deviance from the norm of the origin or course of the right brachiocephalic artery, the left common carotid artery, the left subclavian artery or the proximal vertebral arteries.
Congenital malformation of the ventral wall with partial or total evisceration of the heart outside the thoracic cavity and displacement partially into the abdominal cavity.
Congenital malformation of the thoracic wall with partial or total displacement of the heart outside the thoracic cavity. This feature is associated with sternal cleft or absence of the sternum.
A type of ectopia cordis with the heart partially in the cervical region with a defect of the superior portion of the sternum.
A type of ectopia cordis with the heart partially in the cervical region and withouta defect of the sternum.
Displacement of the heart outside the thoracic cavity and into the abdomen.
Abnormally short chordae tendineae of the mitral valve.
A specific combination of heart defects with a primum atrial septal defect, cleft anterior mitral valve leaflet, and an inlet ventricular septal defect. There are two valve annuli and two valve orifices.
A congenital heart malformation characterised by an atrial septal defect, clefts of mitral and occasionally tricuspid valves, two separate atrioventricular valve annuli and an intact ventricular septum. The typical symptoms are impaired exercise capacity and exertional dyspnoea. The age of onset is variable, but clinical features may not appear until later in life. In contrast to the complete form, patients with partial atrioventricular canal have two separate AV valves, (resulting from fusion of the superior and inferior bridging leaflets), and no large intraventricular communication.
A specific combination of heart defects with a primum atrial septal defect, cleft anterior mitral valve leaflet, and inlet ventricular defect. There is one valve annulus and two valve orifices.
An tricuspid valve that has failed to open.
An atrioventricular valve that has failed to open (atretic).
Cleft in the anterior mitral valve leaflet not associated with an atrioventricular canal defect.
Anomalous insertion of the chordae tendinae or papillary muscles into the contralateral ventricle in the presence of a ventricular septum defect.
An atrioventricular valve that empties into both ventricles. The valve overrides the interventricular septum above a ventricular septum defect.
The condition in which both atria are joined to a single ventricle each by its own atrioventricular valve. The morphology of this ventricle does not allow one to determine if it corresponds to the left or right ventricle.
The condition in which both atria are joined to a single ventricle each by its own atrioventricular valve.
A deviance in the normal connections between two cardiac segements.
Criss-cross atrioventricular valves with a rare cardiac malformation characterized by the two ventricles lying one above the other instead of side by side.
Crossing of the inflow streams of the two ventricles, due to an apparent twisting of the heart about its long axis.
Mirror image atrial arrangement, with morphologic right atrium on the left hand side and morphologic left atrium on the right hand side.
Abnormality of the spatial relationship of the cardiac segments to other components of the heart.
Individuals with anomalous trichromacy possess three types of cones, but one of the three types of cones has an abnormal spectral sensitivity compared to normal cones.
Individuals affected by dichromacy possess only two types of cones, instead of three.
The condition of having both rods and cones, but only a single kind of cone. Affected individuals have good pattern vision in daylight, but cannot distinguish between colors.
Inability to make fine depth discriminations from parallax provided by the two eyes' different positions on the head.
An abnormality of binocular vision, that is of the ability to synthesize the visual inputs from both eyes to a single image with perception of depth.
Splitting of the retina in the macular region.
Pale often indistinct lesions of the macula.
Sectoral aplasia of the iris. [DDD:gblack]
Abnormality of the corneal epithelium, that is of the epithelial tissue that covers the front of the cornea.
Reduced transparency of the central portion of the corneal stroma.
An abnormality of the stroma of cornea, also known as the substantia propria of cornea.
A reduction in the number of corneal endothelial cells.
Abnormality of Descemet's membrane, which is the basement membrane of the corneal endothelium.
Abnormal migration of corneal endothelium.
Abnormality of the corneal endothelium, that is, the single layer of cells on the inner surface of the cornea.
An abnormal anteroposterior thickness of the cornea.
Developmental abnormality in which the lens and cornea are not separated.
Abnormality of the lacrimal gland, i.e., of the almond-shaped gland that secretes the aqueous layer of the tear film for each eye.
An abnormality of the lacrimal punctum, an opening on the eyelid close to the medial canthus that drains tears from the conjunctival sac into the lacrimal duct in the same eyelid.
Complete loss of hearing related to a sensorineural defect.
Persistence of the stapedial artery, which normally regresses during embryonic life.
Sensorineural hearing impairment with childhood onset.
Feeding problem necessitating gastrostomy tube feeding.
Feeding problem necessitating nasogastric tube feeding.
Absence or underdevelopment of the gallbladder.
A lack of intestinal ganglion cells (i.e., an aganglionic section of bowel) affecting the duodenum.
A lack of intestinal ganglion cells (i.e., an aganglionic section of bowel) affecting the small intestine.
Onset prior to birth but after 8 weeks of gestation.
Onset of disease at up to 8 weeks of gestation.
An abnormality of the malleus, an ossicle in the middle ear.
An abnormality of the incus, an ossicle in the middle ear.
Hyposegmented (hypolobulated) or bilobed neutrophil nuclei.
Cognitive, psychiatric or memory anomaly.
An anomaly of the control or production of movement in the central nervous system.
Rhabdomyolysis induced by intake of alcohol.
A medical history of exposure of the mother of a child or fetus to a teratogenic substance during pregnancy.
A medical history of a fetus or child born to a mother with an autoimmune disease.
An abnormally elevated or decreased level of a maternal serum marker analytes used in screening for aneuploidy.
An abnormally low concentration of serum PAPP-A (pregnancy associated plasma protein A), as compared to normal values for gestational-age.
An abnormally high concentration of serum alpha-fetoprotein as compared to normal values for gestational-age.
Fifth finger clinodactyly is defined by a hypoplastic or absent mid-phalanx of the fifth digit. Ultrasound identification of the fetal hand must first be undertaken and then appropriate magnification accomplished. The evaluation requires stretching of the 5 fingers. The diagnosis is established when the middle phalanx of the fifth finger is markedly smaller than normal or absent, which often causes the finger to be curved inward (pmid:16100637).
On prenatal ultrasound, the nasal bone is a thin echogenic line within the bridge of the fetal nose. The fetus is imaged facing the transducer with the fetal face strictly in the midline. The angle of insonation is 90 degrees, with the longitudinal axis of the nasal bone as the reference line. Calibres are placed at each end of the nasal bone. Absence of the nasal bone or measurements below 2.5th percentile are considered significant (pmid:16100637).
A short humerus length is defined as a length below the 2.5th percentile for gestational age or as a measurement less than 0.9 of that predicted by the measured biparietal diameter. The humerus should be measured with the bone perpendicular to the ultrasound beam and with epiphyseal cartilages visible but not included in the measurement (pmid:16100637).
The cisterna magna is measured on a transaxial view of the fetal head angled 15 degrees caudal to the canthomeatal line. The anterior/posterior diameter is taken between the inferior/posterior surface of the vemis of the cerebellum to the inner surface of the cranium. An enlarged cisternal magna is defined by an anterior/posterior diameter of 10 mm or more (pmid:16100637).
An finding upon obstetric ultrasound examination performed at around 16 to 20 weeks of gestation that is abnormal but not clearly identifiable as a fetal anatomic malformation or growth restriction. Such findings are known as soft markers since they are associated with increased risk for fetal aneuploidy or other disorders.
An abnormality of chloride homeostasis or concentration in the body.
Death during adolescence, the period between childhood and adulthood (roughly between the ages of 10 and 19 years).
Intrauterine growth retardation that is at least 3 standard deviations (SD) below average, but not as low as 4 SD, corrected for sex and gestational age.
Demyelination of peripheral sensory nerves.
Delayed myelination in the peripheral nervous system.
An abnormality of the dorsal columns, i.e., of the dorsal portion of the gray substance of the spinal cord. The dorsal column consists of the fasciculus gracilis and fasciculus cuneatus and itself is part of the dorsal funiculus.
Absence or underdevelopment of the cochlea, a spiral shaped cavity in the inner ear, owing to a developmental defect.
A structural anomaly of the internal part of the ear.
An abnormality of the function of the inner ear.
Reduction in diameter of the internal auditory canal.
An abnormality of the morphology of the semicircular canal.
Dilatation of the vestibule of the inner ear.
Underdevelopment of the vestibule of the inner ear.
Complete absence of the vestibule of the inner ear.
Absence of the cochlea, a spiral shaped cavity in the inner ear, owing to a developmental defect.
Incomplete partition I is also known as cystic cochleovestibular malformation, where the cochlea has no bony modiolus, resulting in an empty cystic cochlea. This is accompanied by a dilated cystic vestibule with developmental arrest at the fifth week of gestation.
Incomplete formation of the cochlear partition. The scala vestibuli and scala tympani separated by the cochlear partition, except in the apical turn where the two scalae are in continuity via the helicotrema.
Increased susceptibility to viral skin infections, as manifested by recurrent episodes of viral skin infections.
Increased susceptibility to cutaneous fungal infections, as manifested by recurrent episodes of cutaneous fungal infections.
Reduced pigmentation of hair in patches.
Hair whose growth rate deviates from the norm.
A congenital abnormality of the distribution of hair growth.
An abnormality of the distribution of hair growth that is acquired during the course of life.
An abnormality of the density of hair growth.
An abnormality of the skin that is restricted to a particular body region.
Formation of excess fibrous connective tissue in the tunica intima (innermost layer) of arteries. [HPO:probinson]
An abnormality involving the movement of the eye outwards.
An abnormality of the vermilion border, the sharp demarcation between the lip (red colored) and the adjacent normal skin.
An abnormality of the outline, configuration, or contour of the mouth.
Bilateral temporal scarlike defects, which are said to resemble forceps marks. [DDD:jclayton-smith]
Unilateral underdevelopment of the facial tissues, including muscles and bones.
Any anomaly of a cranial suture, that is one of the six membrane-covered openings in the incompletely ossified skull of the fetus or newborn infant.
Asymmetry of the anterior part of the skull.
Premature synostosis of only the right lambdoid suture.
Premature synostosis of only the left lambdoid suture.
Unicoronal synostosis affecting only the right coronal suture.
Synostosis affecting only the left coronal suture.
Synostosis affecting only one of the coronal sutures. [DDD:awilkie]
A nail plate that has a longitudinal separation with partially separated nails, each with a separate lateral radius of curvature.
Extension of the proximal transverse crease (five finger crease) to the ulnar edge of the palm.
The contour of the foot in lateral profile has a convex shape.
For children from birth to 16 years of age the length of the palm is more than the 97th centile; or, the length of the palm appears relatively long compared to the finger length or the limb length.
The absence of a phalangeal segment of a finger.
A soft tissue prominence of the ventral aspects of the fingertips or toe tips.
EEG with sharp slow waves in the central region. Sharp slow waves are focal sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.
EEG with sharp slow waves in the frontal region. Sharp slow waves are focal sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.
EEG with sharp slow waves in the temporal region. Sharp slow waves are focal sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.
EEG with sharp slow waves in the parietal region. Sharp slow waves are focal sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.
EEG with sharp slow waves in the occipital region. Sharp slow waves are focal sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.
A type of aganglionic megacolon in which the aganglionic segment extends proximal to the sigmoid.
A type of aganglionic megacolon in which the aganglionic segment does not extend beyond the upper sigmoid.
An abnormality of the metencephalon. The metencephalon is the part of the hindbrain that consists of the pons and the cerebellum.
An abnormal level of urinary catecholamine concentration.
An abnormality of calcium concentration in the urine.
An abnormality of the concentration of hydrogencarbonate in the urine.
A type of pulmonary sequestration that occurs within the visceral pleura of normal lung tissue, usually without communication with the tracheobronchial tree.
Increased susceptibility to mycobacterial infections, as manifested by recurrent episodes of mycobacterial infection.
Lack of convexity or prominence of the contour of the ridge between the bottom of the incisura and the confluence of the ascending helix and crus helix.
Discontinuity in the convexity of the inferior margin of the lobe.
A type of cryptotia associated with reduction in size of the antihelix and inferior crus that are affected.
A type of cryptotia associated with reduction in size of the antihelix and superior crus.
Absence of the anterosuperior prominence of the area between the bottom of the incisura and the inner margin of the antihelix.
Positioning of the antitragus at an angle perpendicular to the plane of the ear (oriented away from the plane of the ear).
An abnormality of the stem of the antihelix, which is the part below the bifurcation of the antihelix into the inferior and superior crura.
Antihelical ridge that forms an acute angle between the antitragus and its bifurcation (stem) instead of a gently curving arc.
Supernumerary ridge or crus of the ear arising from the antihelix.
No discernible ridge between concha and triangular fossa and helix.
Elevated ridge(s) of skin starting well below the medial aspect of the lower lid that curves gradually upward toward and/or across the nasal bridge.
Eyelashes that draw the attention of the viewer due to increased density and/or length and/or curl without meeting the criteria of trichomegaly. [pmid:19125427]
An eyebrow that extends laterally beyond the orbital rim rather than turning gently downward at that location.
An abnormal elevation of the C-reactive protein level in serum. [HPO:probinson]
Absence or underdevelopment of the eyelid.
Linear vertical groove in the midline of the forehead, extending from hairline to glabella.
Posterior positioning of the glabella, i.e., of the midline forehead between the supraorbital ridges.
Vertical soft tissue creases in the midline of the forehead, often extending from the hairline to the brow, and seen with facial expression or when the face is at rest.
Facial height (length) is more than two standard deviations below the mean (objective); or an apparent decrease in the height (length) of the face (subjective).
An abnormal shape of the frontal part of the head.
Hypsarrhythmia occurring in one hemisphere.
Occurrence of generalized epileptiform discharges during photic stimulation.
Occurrence of epileptiform discharges in occipital, central, temporal and parietal regions during photic stimulation.
Occurence of epileptiform discharges in occipital and central regions during photic stimulation.
Occurrence of epileptiform discharges in occipital regions during photic stimulation.
Slowing in occipital areas of the scalp EEG.
Generalized slowing of EEG activity at frequencies between 0.5-3 Hz.
Generalized slowing of EEG activity at frequencies between 4-7 Hz.
Slowing at frequencies between 7.5 and 8.5 Hz.
Non-continuous diffuse slowing of electroencephalographic patterns.
EEG showing diffuse slowing without interruption.
Generalized epileptiform discharges of different shapes and frequencies.
EEG with generalized sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.
EEG discharges recorded on the entire scalp typically seen in persons with epilepsy.
EEG with focal sharp transient waves of a duration less than 80 msec followed by a slow wave.
EEG with focal sharp transient waves of a duration between 80 and 200 msec.
EEG with focal sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.
Focal spikes occurring for several seconds.
EEG with focal sharp transient waves of a duration less than 80 msec.
Focal epileptiform discharges of different shapes and frequencies.
Epileptiform discharges being identified at multiple locations in one hemisphere.
Epileptiform discharges identified at multiple locations temporarily in both hemispheres and temporarily in one hemisphere.
Epileptiform discharges being identified at multiple locations in both hemispheres.
Focal EEG discharges that secondarily spread to both hemispheres and can then be recorded over the entire scalp.
Focal epileptiform discharges with spreading to the hemisphere on the same side of the brain.
Focal epileptiform discharges with spreading to contralateral hemisphere but without secondary generalization.
Generalized epileptiform discharges induced by hyperventilation (overbreathing) in cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Focal epileptiform discharges induced by hyperventilation (overbreathing) in cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Electroencephalographic patterns that resemble epileptogenic abnormalities. [HPO:probinson]
EEG dominated by diffuse beta waves (>13 Hz) with occipitally localized alpha waves (8-13 Hz).
EEG dominated by diffuse beta-waves (>13 Hz).
EEG dominated by diffuse alpha-waves (8-13Hz).
An EEG with constitutional variants contains waves that are rare or unusual but not generally pathologic.
Seizures with increase in rate of ongoing movements or inappropriately rapid performance of a movement involving predominantly proximal limb or axial muscles producing irregular sequential ballistic movements, such as pedaling, pelvic thrashing, rocking movements.
Seizures with a decrease in amplitude and/or rate or arrest of ongoing motor activity.
Seizures with regularly repetitive myoclonus, involving the same muscle groups, at a frequency of about 2-3 c/sec.
Auras with sensation of tingling, numbness, electric shock sensations, pain, sense of movement, or desire to move.
Auras with affective, mnemonic or composite perceptual phenomena including illusory or composite hallucinatory events.
Auras with sensation of odor, usually disagreeable.
Auras with abdominal discomfort including nausea, emptiness, tightness, churning, butterflies, malaise, pain, and hunger; sensation may rise to chest or throat. Some phenomena may reflect ictal autonomic dysfunction.
An autonomic seizure without altered responsiveness.
An autonomic seizure with altered responsiveness.
Focal seizures with an objectively documented and distinct alteration of autonomic nervous system function involving cardiovascular, pupillary, gastrointestinal, sudomotor, vasomotor and thermoregularity functions.
Typical absence seizures starting before the age of 4 years.
Atypical absence lasting for more than 30 minutes.
Absence seizures that are additionally characterized by rhythmic bilateral myoclonias of the arms and shoulders synchronous with EEG discharges, with additional tonic components of the arms.
Absence seizures that are additionally characterized by eyelid myoclonia.
Absence seizures that are characterized by additional motor phenomena such as eyelid myoclonias or myoclonic seizure of the upper limbs.
Seizures characterized by impaired consciousness.
A seizure that occurs in the context of a brain insult (systemic, toxic, or metabolic) and may not recur when the underlying cause has been removed or the acute phase has elapsed.
A type of age-related cataract consisting of granular opacities occurring mainly in the central posterior cortex just under the posterior capsule.
An abnormality of the skin adnexa (skin appendages), which are specialized skin structures located within the dermis and focally within the subcutaneous fatty tissue, comprising three histologically distinct structures: (1) the pilosebaceous unit (hair follicle and sebaceous glands); (2) the eccrine sweat glands; and (3) the apocrine glands.
Pale reddish slightly elevated papules and plaques of 0.5-3 cm in diameter and not accompanied by pruritus.
Absence or developmental hypoplasia of the sweat glands.
A furuncle (boil) is a skin infection involving an entire hair follicle and nearby skin tissue. Chronic furunculosis refers to recurrent episodes of furuncles, often caused by recurrent staphylococcus infection.
Any abnormality of the morphology of the major calices or minor calices of the kidney.
A condition characterized by necrosis of the mucosal and submucosal layers of the esophagus not related to ingestion of caustic or other injurious agents. Endoscopically, there is a dark lesion ('black esophagus') distributed in a circumferential manner in the distal one-third of the esophagus with or without exudates. There is involvement of the distal esophagus ending sharply at the gastroesophageal junction.
An abnormality of the melanosomes, i.e., of the cellular organelles in which melanin pigments are synthesized and stored within melanocytes (the cells that produce pigment in the dermis).
An abnormality of the morphology of the epidermis.
Any abnormality of the physiological function of the skin.
Any morphological abnormality of the skin.
An abnormality in the production or cellular release of tumor necrosis factor.
An abnormality in the production or cellular release of interleukins (a class of cytokines).
An abnormality in the production or cellular release of interferons (a class of cytokines).
An abnormality in the production or cellular release of a chemokine (a class of cytokines).
An impairment in the production by leukocytes of NFKB1-dependent cytokines such as tumor necrosis factor-alpha and interferon-alpha.
An abnormality in the production or cellular release of a cytokine (i.e., any of the non-antibody proteins made by inflammatory leukocytes and some non-leukocytic cells that affect the behavior of other cells).
Abnormality of the cytokine levels in the blood, i.e., an abnormality of any of the non-antibody proteins made by inflammatory leukocytes and some non-leukocytic cells that affect the behavior of other cells.
An abnormality of the concentration or function of circulating immune proteins.
An abnormality in the amount of volume occupied by intravascular blood.
Developmental dysplasia of dentin or both the primary dentition and the permanent dentition.
A form of hypomineralization of enamel characterized by a chalky appearance of the enamel with orange, brown, or white color.
A form of hypomineralization of enamel characterized by reduced calcification.
An abnormal conical morphology of either maxillary primary incisor tooth or maxillary permanent incisor tooth or both.
An abnormal conical morphology of the primary incisor.
An abnormality of morphology of premolar tooth.
A localized form of developmental hypoplasia of the dental enamel.
An abnormality of morphology of permanent molar.
An abnormality of morphology of molar tooth.
The presence of an altered number of of the incisor teeth..
An abnormality of morphology of the incisor tooth.
An abnormality of the structure or composition of the teeth.
Developmental dysplasia of dentin affecting only the primary dentition. [HPO:ibailleulforestier]
A localized form of periodontitis. [HPO:ibailleulforestier]
Agenesis of either mandibular second permanent molar or maxillary second permanent molar. [HPO:ibailleulforestier]
Agenesis of either maxillary first permanent molar or mandibular first permanent molar or both.
Agenesis of secondary molar tooth. [HPO:ibailleulforestier]
Agenesis of maxillary premolar. [HPO:ibailleulforestier]
Agenesis of premolar tooth. [HPO:ibailleulforestier]
Agenesis of one or more upper lateral secondary incisor.
Agenesis of one or more maxillary lateral incisor, comprising the maxillary lateral primary incisor. [HPO:ibailleulforestier]
Agenesis of lower primary incisor. [HPO:ibailleulforestier]
Agenesis of upper central primary incisor.
The presence of an altered number of of permanent teeth.
An abnormal concentration of corticotropin in the blood.
Aplasia or developmental hypoplasia of the cervical vertebral column.
An abnormality of the intrahepatic bile duct.
An altered ability of the kidneys to void urine and/or specific substances.
An abnormality of the cortex of the kidney.
An impairment of a fructose metabolic process.
An abnormality of the homeostasis (concentration) of iron cation.
An abnormality of the homeostasis (concentration) of transition element cation.
An abnormality of blood circulation. [HPO:probinson]
Aplasia or developmental hypoplasia of the vagina.
Abnormal functionality of the cardiovascular system.
An abnormality of the gastrointestinal tract. [HPO:probinson]
An abnormality of prostaglandin metabolism.
An abnormality of unsaturated fatty acid metabolism.
An abnormality of the metabolism of mucopolysaccharide.
An abnormality of chromosome condensation.
An abnormality of the concentration of glucose in the urine.
An abnormality of the concentration of glucose in the blood.
An abnormality of the metabolism/homeostasis of a carbohydrate.
An abnormality of the metabolism of polysaccharide.
An increase in the number of spontaneous sister chromatid exchanges observed in cell culture of lymphocytes or other cells.
An abnormality of monocarboxylic acid metabolism.
An abnormality of dicarboxylic acid metabolism.
Abnormality of the striatum, which is the largest nucleus of the basal ganglia, comprising the caudate, putamen and ventral striatum, including the nucleus accumbens.
An abnormality of the abdominal musculature.
An abnormality of blood coagulation, common pathway.
An abnormality of the intrinsic pathway (also known as the contact activation pathway) of the coagulation cascade.
An abnormality of the extrinsic pathway (also known as the tissue factor pathway) of the coagulation cascade.
An abnormality of the morphology or counts of the cells that make up the immune system.
An abnormal increase or decrease in the level of lipoprotein cholesterol in the blood.
A functional abnormality of the immune system.
Absence of the Lutheran antigen (a type I integral membrane glycoprotein) from the surface of red blood cells.
An abnormality of an erythrocyte cell surface molecule.
An abnormality of glycolipid metabolism.
An abnormality of liposaccharide metabolism.
An abnormality of phytanic acid metabolism.
An abnormality of long-chain fatty acid metabolism.
By the 14th week of gestation it is nearly always possible to visualized the fluid-filled fetal stomach bubble on prenatal sonography. This term refers to the absence of a normal fetal stomach bubble on fetal ultrasonography performed at around 16 to 20 weeks' gestation.
A kind of bronchopulmonary sequestration that is completely discrete from the normal lung and is surrounded by separate pleura.
A kind of bronchopulmonary sequestration that is incorporated into the normal surrounding lung.
A kind of ventriculomegaly occurring in the fetal period and usually diagnosed by prenatal ultrasound. Cerebral ventriculomegaly is defined by atrial measurements 10 mm or more. Mild ventriculomegaly (MVM) is defined as measurements between 10 and 15 mm. Measurements are obtained from an axial plane at the level of the thalamic nuclei just below the standard image to measure the BPD (pmid:16100637).
An first-trimester prenatal ultrasound finding of abnormal blood flow in the umbilical vein.
An first-trimester prenatal ultrasound finding of abnormal blood flow in the ductus venosus.
A finding of a focus of increased echogenicity upon prenatal ultrasound examination of the fetus. The foci may be present in one or both ventricles. Echogenic intracardiac focus (EICF) is defined as a focus of echogenicity comparable to bone, in the region of the papillary muscle in either or both ventricles of the fetal heart.
Absence or underdevelopment of the nasal bone.
An abnormality of the nasal bone, comprising the left nasal bone and the right nasal bone.
An abnormality of the lower urinary tract.
An abnormality of the upper urinary tract.
An abnormality of a xanthine metabolic process.
An abnormality of a nucleobase metabolic process.
An abnormality of monovalent inorganic cation homeostasis.
An abnormality of the metabolism of orotic acid.
An abnormality of divalent inorganic cation homeostasis.
A cataract that affects the posterior part of the cortex of the lens.
An abnormality of a homocysteine metabolic process.
An abnormality of a cysteine metabolic process.
An abnormality of a tyrosine metabolic process.
An abnormality of an alanine metabolic process.
An abnormality of a pyruvate family amino acid metabolic process.
An abnormality of a valine metabolic process.
An increased concentration of isoleucine in the blood.
An abnormality of a isoleucine metabolic process.
An abnormality of a arginine metabolic process.
An abnormality of a lysine metabolic process.
An abnormality of a proline metabolic process.
An abnormality of a histidine metabolic process.
An abnormality of a glutamine metabolic process.
An abnormality of a glutamine family amino acid metabolic process.
An abnormality of methionine metabolic process.
Abnormality of a threonine metabolic process.
Abnormality of a aspartate family amino acid metabolic process.
An abnormality of the metabolism of sarcosine.
An elevated urinary concentration of sarcosine.
An abnormality of a glycine metabolic process.
An abnormality of a serine family amino acid metabolic process.
An abnormality of L-phenylalanine metabolic process.
Abnormality of a branched chain family amino acid metabolic process.
Morbus Koehler is a Juvenile aseptic necrosis affecting the Os naviculare pedis.
Shortening of the extremities affecting primarily the distal parts of the limbs (hands and feet) in relation to the other segments of the limbs.
The presence of an abnormally large hypoechoic space in the posterior fetal neck (usually detected on prenatal ultrasound examination).
A type of strabismus in which only one eye is affected. Unilateral strabismus is to be distinguished from alternating strabismus, in which either of the eyes 'squints' at different times. [HPO:probinson]
An abnormal level of a circulating protein in the blood. [HPO:probinson]
A type of dyssynergia affecting eye movements and characterized by the inability to smoothly follow a visual target across the visual field.
A type of motor delay characterized by a delay in acquiring the ability to control the fingers and hands.
Epileptiform discharges induced by hyperventilation (overbreathing) in cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
Complexes of spikes (<70 ms) and sharp waves (70-200 ms), which are sharp transient waves that have a strong association with epilepsy, in cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
The presence of complexes of spikes and waves (>3.5 Hz) in electroencephalography (EEG).
The presence of complexes of spikes and waves (2.5-3.5 Hz) in electroencephalography (EEG).
The presence of complexes of slow spikes and slow waves (<2.5 Hz) in electroencephalography (EEG).
Multifocal slowing of cerebral electrical activity recorded along the scalp by electroencephalography (EEG).
An increased concentration of copper in the urine.
An abnormal concentration of copper. [HPO:probinson]
Spontaneous pain is a kind of neuropathic pain which occurs without an identifiable trigger.
Pain is an unpleasant sensation that can range from mild, localized discomfort to agony, whereby the physical part of pain results from nerve stimulation and is often accompanied by an emotional component. This term groups abnormalities in pain sensation presumed to result from abnormalities related to the specific nerve fibers that carry the pain impulses to the brain.
An overlap of the bony plates of the skull in an infant, with or without early closure.
A type of seizure characterized by crying or an outburst of crying as a major feature.
Hair growth from a single point on the scalp in any location other than lateral to the midline and close to the vertex of the skull.
Inner aspect of the upper lip vermilion (normally apposing the teeth) visible in a frontal view, i.e., the presence of an everted upper lip.
Increased pigmentation, either focal or generalized, of the skin surrounding the vermilion of the lips.
Reduced ability affecting mainly visuospatial cognition which may be tested using pattern construction (for example by Differential Ability Scales, which test a person's strengths and weaknesses across a range of intellectual abilities).
Underdevelopment of the interstitial (Leydig) cells of the testis. These cells produce testosterone.
A subtype of skin dimples occurring in the shoulder region.
Marked widening of the major bronchi that may be predispose to chronic respiratory tract infection.
Marked widening of the trachea and major bronchi that may be predispose to chronic respiratory tract infection.
The presence of a cyst, fistula, or abscess in the sacrococcygeal region (gluteal crease) characteristically accompanied by hair and skin folds.
Hyperkeratosis affecting the palm of the hand.
An abnormality of the premaxilla [UBERON_0002244], the most anterior part of the maxilla that usually bears the central and lateral incisors and includes the anterior nasal spine and inferior aspect of the piriform rim. The premaxilla contains the bone and teeth of the primary palate.
Absence of the Premaxilla, which is the embryonic structure that forms the anterior part of the maxilla.
Absence or underdevelopment of the premaxilla.
Nodular changes affecting the eyelids may have many different causes such as cystic lesions (chalaziae, hordeolae), lipogranulomas, melanomas, infectious diseases (Molluscum contagiosum) and many more.
The eyebrows extend towards - or even all the way down to - the margin of the upper eyelid.
A developmental defect characterized by absence of the retina.
Rupture of the eyeball not due to trauma.
An abnormality of the distribution of hair growth.
An abnormality of the texture of the hair.
Syndactyly with fusion of toes three to five.
Syndactyly with fusion of toes two to five.
Syndactyly with fusion of toes one to four.
Syndactyly with fusion of toes one and two.
Syndactyly with fusion of fingers three to five.
Syndactyly with fusion of fingers one to five (complete syndactyly of all fingers of the hand).
Syndactyly with fusion of fingers one to four.
Syndactyly with fusion of fingers one to three.
Syndactyly with fusion of fingers four and five.
Syndactyly with fusion of fingers one and two.
A nuclear cataract with a triangular form.
A type of congenital cataract in which the opacity follows the anterior or posterior Y suture.
A Lamellar cataract with a pulverulent (punctate, ""dust-like"" opacities) appearance.
Syndactyly with fusion of fingers two to five.
An abnormally reduced level of alkaline phosphatase, placental type in the blood.
An abnormally reduced level of alkaline phosphatase, intestinal type in the blood.
An abnormally reduced level of liver isoforms of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
An abnormally reduced level of kidney isoforms of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
An abnormally reduced level of bone isoforms of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
An abnormally reduced level of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
An abnormally increased level of alkaline phosphatase, placental type in the blood.
An abnormally increased level of alkaline phosphatase, intestinal type in the blood.
An abnormally increased level of kidney isoforms of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
Enuresis occurring during waking hours of the day.
The presence of an abnormal curvature of the vertebral column.
An abnormality of the third metatarsal bone.
A congenital defect characterized by absence of the Maxilla.
Underdevelopment of the anterior nasal spine of maxilla.
An abnormality of the Diencephalon, which together with the cerebrum (telencephalon) makes up the forebrain.
A developmental defect characterized by the absence of the Third ventricle.
Patchy (irregular) changes in bone mineral density. These changes can either be patchy reduction or increase of mineral density as seen on x-rays. Depending on the pathomechanism and the underlying disease, these changes can either appear solely as reduction or increase or as a combination of both (patches of bone showing an increased density while others are affected by reduction of mineral density).
Patchy (irregular) reduction in bone density. This can take on many forms depending on severity and distribution as can be seen on x-rays.
A developmental defect characterized by aplasia of the Falx cerebri.
An abnormality of the Meninges, including any abnormality of the Dura mater, the Arachnoid mater, and the Pia mater.
An abnormal degree of flatness of the Ala of nose, which can be defined as a reduced nasal elevation index (lateral depth of the nose from the tip of the nose to the insertion of the nasal ala in the cheek x 100 divided by the side-to-side breadth of the nasal alae).
Any abnormal increase or reduction in skin elasticity.
Absence of the distal phalanges of the toes.
Absence or abnormal closure of the midnasal cavity.
Abnormality of the nasal cavity (the cavity includes and starts at the nares and reaches all the way through to the and includes the choanae, the posterior nasal apertures).
An abnormally increased level of liver isoforms of alkaline phosphatase, tissue-nonspecific isozyme in the blood.
Reduced ability to perceive certain odorants (implies that the sense of smell is maintained for other classes of odorants).
Reduced ability to detect any qualitative olfactory sensation.
Inability to perceive certain odorants (implies that the sense of smell is maintained for other classes of odorants).
Inability to detect any qualitative olfactory sensation.
Any abnormality of the epiphyses of the feet.
Any abnormality affecting the cortex of the humerus.
Absence or underdevelopment of the anterior pituitary gland, also known as the adenohypophysis.
Any abnormality of the proximal epiphysis of the ulna.
Any abnormality of the distal epiphysis of the ulna.
Any abnormality of the distal epiphysis of the humerus.
Any abnormality of the proximal epiphysis of the humerus.
Any abnormality of the distal epiphysis of the radius.
Any abnormality of the proximal epiphysis of the radius.
Any abnormality of the distal epiphysis of the fibula.
Any abnormality of the proximal epiphysis of the fibula.
Any abnormality of the proximal epiphysis of the tibia.
Any abnormality of the distal epiphysis of the femur.
An abnormally low concentration of serum alpha-fetoprotein as compared to normal values for gestational-age.
A hamartoma (disordered proliferation of mature tissues) which can originate from any tissue of the eye.
Y-shaped metatarsals are the result of a partial fusion of two metatarsal bones, with the two arms of the Y pointing in the distal direction. Y-shaped metatarsals may be seen in combination with polydactyly.
This term applies if the Epiglottis is absent or hypoplastic.
An abnormality of the clivus, which is the inclined bony region of the posterior cranial fossa located between the sella turcica and the foramen magnum.
Weakness of both lower extremities with sparing of the upper extremities. Paraplegia refers to a severe or complete loss of strength, whereas paraparesis refers to a relatively mild loss of strength.
A degree of pneumatization that is increased compared to age-related norms.
The presence of ectopic thymus tissue. Normally, cells of the ventral bud of the third pharyngeal pouch detach and migrate in the eighth gestational week caudally and medially towards the location of the mature thyroid. They migrate further retrosternally into the superior mediastinum. There are two main ways ectopic thymus tissue can develop. Either cells detach along the descensus path and proliferate, thereby forming accessory thymus tissue, or the entire gland fails to descend.
Absence or underdevelopment of the thymus.
An ability of the toe joints to move beyond their normal range of motion.
A difference in size or shape between the left and right foot.
An abnormal limitation of the mobility of the ankle joint.
A bending or abnormal curvature of the fibula.
The ability of the knee joint to extend beyond its normal range of motion (the lower leg is moved beyond a straight position with respect to the thigh).
Abnormal increase in size of the lower limbs (due to an increase of the size of cells).
Amniotic constriction rings affecting the legs.
Shortening of the legs predominantly affecting terminal parts of the leg in relation to the upper and middle arm segments.
Absence or underdevelopment of the palmar creases.
An abnormality of the hypothenar eminence, i.e., of the muscles on the ulnar side of the palm of the hand (i.e., on the side of the little finger).
The ability of the elbow joint to move beyond its normal range of motion.
Amniotic constriction rings affecting the arms.
Shortening of the arms predominantly affecting terminal parts of the arm in relation to the upper and middle limb segments.
Aplasia (absence) of the urinary bladder.
Absence or underdevelopment of the urinary bladder.
An abnormality in the synthesis or catabolism of heme. Heme is composed of ferrous iron and protoporphyrin IX and is an essential molecule as the prosthetic group of hemeproteins such as hemoglobin, myoglobin, mitochondrial and microsomal cytochromes.
Increased urinary excretion of oligosaccharides (low molecular weight carbohydrate chains composed of at least three monosaccharide subunits), derived from a partial degradation of glycoproteins.
Absence or underdevelopment of the testes.
Aplasia or developmental hypoplasia of the ovary.
Abnormality of the female genital system.
Abnormally increased width of the greater sacrosciatic notch.
An abnormality of the sacrosciatic notch, i.e., the deep indentation in the posterior border of the hip bone at the point of union of the ilium and ischium.
Absence or underdevelopment of the spleen.
A bifid or bifurcated appearance of the femur as seen on x-rays, possible appearing as a more or less severe bowing of the upper leg. Might be associated with hip dysplasia on the affected side.
In contrast to forms of polydactyly where the supernumerary digit (this can either be a rudimentary or a completely 'normal' digit) is either located postaxial (on the ulnar side of the hand, next to the little finger), preaxial (on the radial side of the hand, next to the thumb) or mesoaxial (somewhere central, between thumb and little finger), a supernumerary digit may also be placed ectopically, meaning anywhere else except post-,meso- or preaxial. In the literature this is sometimes refered to as Disorganisation-like Syndrome (OMIM223200).
In contrast to forms of polydactyly where the supernumerary digit (this can either be a rudimentary or a completely 'normal' digit) is either located postaxial (on the fibular side of the foot, next top the little toe), preaxial (on the tibial side of the foot, next to the big toe) or mesoaxial (somewhere central, between big and little toe), a supernumerary digit may also be placed ectopically, meaning anywhere else except post-,meso- or preaxial. In the literature this is sometimes refered to as Disorganisation-like Syndrome (OMIM223200).
Complete duplication of a phalanx of second toe.
Partial duplication of a phalanx of second toe.
Partial duplication of middle phalanx of second toe.
Complete duplication of middle phalanx of second toe.
Partial duplication of the distal phalanx of second toe.
Complete duplication of the distal phalanx of second toe.
A deviation from the normal straight form of the distal phalanx of the 2nd toe.
An abnormal morphology of the distal phalanx of the second toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
A deviation from the normal straight form of the middle phalanx of the 2nd toe.
An abnormal morphology of the middle phalanx of the second toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
A deviation from the normal straight form of the proximal phalanx of the 2nd toe.
An abnormal morphology of the proximal phalanx of the 2nd toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Absence (agenesis) or underdevelopment of one or more of the proximal phalanges of the 2nd toe.
An anomaly of the proximal phalanx of third toe.
Fusion of the interphalangeal joints of the 2nd toe.
Absence or underdevelopment of the abdominal musculature.
Absence or underdevelopment of the diaphragm.
Absence or underdevelopment of the breasts.
Any abnormality of the spinal meninges, the system of membranes (dura mater, the arachnoid mater, and the pia mater) which envelops the spinal cord.
Absence or underdevelopment of the tongue.
Underdevelopment or absence of the uvula.
Distance between the labial point of the incisive papilla to the midline junction of the hard and soft palate more than 2 SD below the mean (objective) or apparently decreased length of the hard palate (subjective). [pmid:19125428]
Any abnormality of the sublingual glands, which are the salivary glands that are located beneath the floor of the mouth anterior to the submandibular glands.
Any abnormality of the submandibular glands, which are the salivary glands that are located beneath the floor of the mouth, superior to the digastric muscles.
Fibrous band between the mucosal surfaces of the upper and lower alveolar ridges.
A secondary ossification center in the proximal phalanges of the hand that is distinct from the normal epiphysis that does not contribute to the longitudinal growth of a tubular bone.
Epiphyses of the proximal phalanges of the hand are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
An abnormality of the proximal phalanges of the hand in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
A secondary ossification center in the middle phalanges of the hand that is distinct from the normal epiphysis that does not contribute to the longitudinal growth of a tubular bone.
Epiphyses of the middle phalanges of the hand are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
Fragmented appearance of the epiphyses of the middle phalanges of the hand.
An abnormality of the middle phalanges of the hand in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
A secondary ossification center in the distal phalanges of the hand that is distinct from the normal epiphysis that does not contribute to the longitudinal growth of a tubular bone.
An abnormality of the distal phalanges of the hand in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Any anomal of distal epiphysis of phalanx of finger.
The normal epiphysis of the fifth metacarpal is localised at the distal end of the metacarpal bone. This term aplies if an accesory epiphysis, located at the proximal end of the metacarpal bone, is present.
Any abnormality of the epiphysis of the fifth metacarpal bone.
The normal epiphysis of the fourth metacarpal is localised at the distal end of the metacarpal bone. This term aplies if an accesory epiphysis, located at the proximal end of the metacarpal bone, is present.
Any abnormality of the epiphysis of the 4th metacarpal bone.
The normal epiphysis of the third metacarpal is localised at the distal end of the metacarpal bone. This term aplies if an accesory epiphysis, located at the proximal end of the metacarpal bone, is present.
Any abnormality of the epiphysis of the third metacarpal bone.
The normal epiphysis of the second metacarpal is localised at the distal end of the metacarpal bone. This term aplies if an accesory epiphysis, located at the proximal end of the metacarpal bone, is present.
Any abnormality of the epiphysis of the second metacarpal bone.
A foot deformity resulting due to an abnormality affecting the bones of the foot (as well as muscle and soft tissue). In contrast if only the muscle and soft tissue are affected the term positional foot deformity applies.
The joint between the first metatarsal and the proximal phalanx of the first (big) toe cannot be straightened actively or passively.
The interphalangeal joint of the big toe cannot be straightened actively or passively.
Chronic loss of joint motion in the tarsometatarsal joint of the hallux due to structural changes in non-bony tissue. The tarsometatarsal joints of the feet are also called Lisfranc's joints.
An increase in width of one ore more proximal toe phalanges.
Increased width of the distal phalanx of toe of one or more toes.
Increased width of phalanx of toe of one or more toes.
Absence of the epiphyses of the phalanges of the toes.
The epiphysis of the 1st metatarsal are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
A conical (cone-shaped) appearance of the epiphysis of the first metatarsal of the foot.
The epiphysis of the 1st metatarsal surrounds the diaphysis, having a bracket-like form.
Failure to form (agenesis) of the epiphysis of the 1st metatarsal.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the distal phalanx of the hallux.
The epiphysis of the distal phalanx of the hallux surrounds the diaphysis, having a bracket-like form.
Failure to form (agenesis) of the epiphysis of the distal phalanx of the hallux.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the proximal phalanx of the hallux.
The epiphysis of the proximal phalanx of the hallux surrounds the diaphysis, having a bracket-like form.
Failure to form (agenesis) of the epiphysis of the proximal phalanx of the hallux.
In contrast to the metatarsals 2-5, the first metatarsal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the digits 2-5, whereas the proximal phalanx of the big toe is equivalent to the middle phalanges of the other digits. This term applies to abnormalities affecting the proximal phalanx of the hallux.
In contrast to the metatarsals 2-5, the first metatarsal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the digits 2-5, whereas the proximal phalanx of the big toe is equivalent to the middle phalanges of the other digits. This term applies to abnormalities of the epiphysis of the first metatarsal bone.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the hallux.
A developmental defect consisting in the duplication of part of the first metatarsal bone.
A developmental defect consisting in the complete duplication of the first metatarsal bone.
Partial duplication of the proximal phalanx of big toe.
Complete duplication of the proximal phalanx of big toe.
Partial or complete duplication of the proximal phalanx of big toe.
A deviation from the normal straight form of the proximal phalanx of the big toe.
An abnormal morphology of the proximal phalanx of the big toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
A deviation from the normal straight form of the distal phalanx of the big toe.
An abnormal morphology of the distal phalanx of the big toe, with a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
An increase in width of the distal phalanx of the big toe.
Dissolution or degeneration of bone tissue of the first metatarsal.
A deviation from the normal straight shape of a proximal phalanx of the 1st metatarsal bone.
An abnormal morphology of the firstmetatarsal bone, which is short and wide and tapers distally, and lacks the normal diaphyseal constriction.
Absence or underdevelopment of the first metatarsal bone.
An anomaly of the first metatarsal bone.
In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the big toe is embryologically equivalent to the middle phalanges of the other digits, whereas the first metatarsal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Aplasia or Hypoplasia affecting the 5th metacarpal.
Absence of the fourth long bone of the hand.
Aplasia or Hypoplasia affecting the 4th metacarpal.
Absence of the third long bone of the hand.
Aplasia or Hypoplasia affecting the 3rd metacarpal.
Absence of the second long bone of the hand.
Aplasia or Hypoplasia affecting the 2nd metacarpal.
This term applies to a triangular shaped 1st metacarpal.
Uneven increase in bone density within the 1st metacarpal.
Dissolution or degeneration of bone tissue of the 1st metacarpal.
A deviation from the normal straight shape of the first metacarpal.
The presence of short and wide 1st metacarpal which tapers distally (""bullet shaped"").
Increased width of the 1st metacarapal. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Aplasia or Hypoplasia affecting the 1st metacarpal. In contrast to the metacarpals 2-5, the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the digits 2-5 (whereas the proximal phalanx of the thumb is equivalent to the middle phalanges of the other digits).
Abnormally small size of the epiphysis of the 1st metacarpal with respect to age-dependent norms.
The epiphysis of the first metacarpal is localized at the proximal end of the metacarpal bone although an accessory epiphysis may be located at the distal end of the metacarpal.
The epiphysis of the 1st metacarpal are hard and dense like ivory. Such an epiphysis has a uniformly dense appearance on radiographs.
Uneven radiographic opacity of the epiphysis of the 1st metacarpal.
Epiphysis of the 1st metacarpal having multiple bony fragments.
Abnormally large size of the epiphyses of the 1st metacarpal with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the 1st metacarpal, producing a 'ball-in-a-socket' appearance.
An epiphysis that curves around from its transverse orientation to a longitudinal one from proximal to distal along one side of the phalanx, thus resembling the letter 'C' and forming a bracket around the diaphysis. This results in a so called delta phalanx characterized by a triangular or trapezoidal shaped bone with a C-shaped epiphyseal plate.
In contrast to the metacarpals 2-5, the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the digits 2-5 (whereas the proximal phalanx of the thumb is equivalent to the middle phalanges of the other digits). The epiphysis of the first metacarpal is localized at the proximal end (as seen in the proximal phalanges of the other digits), whereas the epiphyses of the other metacarpal bones are located at the distal end. This term applies if the epiphysis of the 1st metacarpal is in any way abnormal, referring to age and gender depending norms, as seen on x-rays.
Any abnormality of the fifth metacarpal bone.
Any abnormality of the fourth metacarpal bone.
Any abnormality of the third metacarpal bone.
Any abnormality of the second metacarpal bone.
A structural anomaly of the first metacarpal.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the middle phalanges of the hand. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the proximal phalanges of the hand. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
A complete duplication affecting one or more of the middle phalanges of the hand. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accessory bone appearing in the proximo-distal axis on x-rays, this is actually a different entity called a pseudoepiphysis (see corresponding terms) sometimes also referred to as hyperphalangism.
A complete duplication affecting one or more of the distal phalanges of the hand.
A complete duplication affecting one or more of the proximal phalanges of the hand. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accesory bone appearing in the proximo-distal axis on x-rays, this is actually a different entity called a Pseudoepiphyses (see according terms) sometimes also refered to as Hyperphalangism.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the hand. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
A complete duplication affecting one or more of the phalanges of the hand. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accesory bone appearing in the proximo-distal axis on x-rays, is a different entity called a Pseudoepiphyses (see according terms) sometimes also refered to as Hyperphalangism.
Partial or complete duplication of the fifth proximal phalanx of hand, seen on x-rays as a broad and/or bifid phalanx.
Partial duplication of the fifth middle phalanx of hand, seen on x-rays as a broad and/or bifid phalanx.
Complete duplication of the fifth proximal phalanx of hand.
Complete duplication of the fifth middle phalanx of hand.
Complete duplication of the distal phalanx of little finger.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the 5th finger. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
A complete duplication affecting one or more of the phalanges of the 5th finger. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accesory bone appearing in the proximo-distal axis on x-rays, this is actually a different entity called a Pseudoepiphyses (see according terms) sometimes also refered to as Hyperphalangism.
Partial duplication of the fourth proximal phalanx of hand, seen on x-rays as a broad and/or bifid phalanx.
Partial duplication of the middle phalanx of ring finger, seen on x-rays as a broad and/or bifid phalanx.
Complete duplication of the fourth proximal phalanx of hand.
Complete duplication of the middle phalanx of ring finger.
Complete duplication of the distal phalanx of ring finger.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the 4th finger. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
A complete duplication affecting one or more of the phalanges of the 4th finger. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accesory bone appearing in the proximo-distal axis on x-rays, this is actually a different entity called a Pseudoepiphyses (see according terms) sometimes also refered to as Hyperphalangism.
Partial duplication of the third proximal phalanx of hand, seen on x-rays as a broad and/or bifid phalanx.
Partial duplication of the middle phalanx of middle finger, seen on x-rays as a broad and/or bifid phalanx.
Complete duplication of the third proximal phalanx of hand.
Complete duplication of the middle phalanx of middle finger.
Complete duplication of the distal phalanx of middle finger
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the 3rd finger. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
A complete duplication affecting one or more of the phalanges of the 3rd finger. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accesory bone appearing in the proximo-distal axis on x-rays, this is actually a different entity called a Pseudoepiphyses (see according terms) sometimes also refered to as Hyperphalangism.
A complete duplication affecting one or more of the phalanges of the 2nd finger. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accesory bone appearing in the proximo-distal axis on x-rays, is a different entity called a Pseudoepiphyses (see according terms) sometimes also refered to as Hyperphalangism.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the 2nd finger. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
Partial duplication of the Second proximal phalanx of hand, seen on x-rays as a broad and/or bifid phalanx.
Complete duplication of the Second proximal phalanx of hand.
Partial duplication of the middle phalanx of index finger, seen on x-rays as a broad and/or bifid phalanx.
Complete duplication of the middle phalanx of index finger.
Complete duplication of the distal phalanx of index finger.
Lack or loss of the soft tissues between the zygomata and mandible.
Absence or underdevelopment of the nasal septum.
Asymmetry or size difference between the left and right nostril.
Underdevelopment or absence of the nose or parts thereof.
Persistence of the hyaloid artery, which is the embryonic artery that runs from the optic disk to the posterior lens capsule may persist; the site of attachment may form an opacity. The hyaloid artery is a branch of the ophthalmic artery, and usually regresses completely before birth.
Aplasia or developmental hypoplasia of the tragus.
Abnormality of the temporal bone of the skull, which is situated at the sides and base of the skull roughly underlying the region of the face known as the temple.
Decreased thickness of thehelix of the ear.
Abnormally prominent ear helix. [HPO:probinson]
Distortion of the course of the normal folds of the ear and the appearance of supernumerary crura and folds.
An abnormality of the antitragus, which is a small tubercle opposite to the tragus of the ear. The antitragus and the tragus are separated by the intertragic notch.
Increased thickness of the external ear.
The presence of telangiectasia of the ear.
Abnormally increased hair growth with a localized distribution.
Abnormality of the growth of secondary sexual hair, which normally ensues during puberty. In males, secondary sexual hair usually comprises body hair, including underarm, abdominal, chest, and pubic hair. In females, secondary sexual hair usually comprises a lesser degree of body hair, most prominently underarm and pubic hair.
An abnormality of hair pigmentation (color).
Abnormally wide (broad) distal phalanx of finger of all fingers.
The presence of cerebellar signs and symptoms such as lack of balance associated with quadrupedal gait (locomotion on all four extremities with a 'bear-like' gait with the legs held straight).
Short and wide proximal phalanges that taper distally . Bullet-shaped phalanges lack the normal diaphyseal constriction.
Increased width of the proximal phalanges of the finger.
Fusion of a middle phalanx of a finger with another bone.
Any of the middle phalanges with short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Short and wide distal phalanges that taper distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
The distal parts of the limbs are missing leading to a stump formation.
Peromelia affecting only the lower limbs. That is, the distal parts of the leg are missing leading to stump formation.
Peromelia affecting only the upper limbs. That is, the distal parts of the arm are missing leading to stump formation.
A form of heart failure characterized by reduced cardiac output. This may be seen in patients with heart failure owing to ischemic heart disease, hypertension, cardiomyopathy, and other causes.
The presence of a reduced number of teeth as in Hypodontia or as in Anodontia.
Absence of one or more of the phalanges of the hand.
Absence or underdevelopment of the quadriceps muscle.
Absence or underdevelopment involving the musculature of the thigh.
Absence or underdevelopment of the triceps muscle.
Absence or underdevelopment of the biceps muscle.
A zone of darker pigmentation around the central part of the iris with a roughly cloverleaf or flower shape.
Pyramidal skinfold extending from the base to the top of the nails is a rare and distinctive anomaly seen in popliteal pterygia syndrome.
An abnormality of the spinal dura mater, which is the outermost of the three layers of the meninges surrounding the spinal cord.
Absence of the parotid gland. [HPO:curators]
Pseudarthrosis, or ""false joint"" of the tibia is the result of a developmental failure in the tibia progressing to spontaneous fracture and subsequent fibrous nonunion. The fracture is rarely present at birth but commonly develops during the first 18 months of life.
The presence of a hamartoma of the cerebrum.
A lesion located beneath a fingernail or toenail.
Hypomelanotic macules (""ash leaf spots"") are white or lighter patches of skin that may appear anywhere on the body and are caused by a lack of melanin. White ash leaf-shaped macules are considered to be characteristic of tuberous sclerosis.
A cystadenoma, an epithelial tumor, that originates within the head of the epididymis.
Chilblains are acral ulcers. [HPO:curators]
Chronic cerebrospinal fluid (CSF) lymphocytosis is defined as the finding, in at least two serial CSF examinations, of more than 5 cells per cubic millimeter.
Chronic loss of joint motion in one or more distal interphalangeal joints of the fingers.
An abnormality of the thumb in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of one or more epiphyses of the thumb.
A triangular appearance of the epiphysis of the distal phalanx of the thumb of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the distal phalanx of the thumb.
Abnormally small size of the epiphysis located at the proximal end of the distal phalanx of the thumb with respect to age-dependent norms.
A pseudoepiphysis (which is a secondary ossification center distinct from the normal epiphysis) of the distal phalanx of the thumb.
Sclerosis of the epiphysis of the distal phalanx of the thumb, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Uneven radiographic opacity of the epiphysis of the distal phalanx of the thumb.
Epiphysis of the distal phalanx of the thumb having multiple bony fragments.
An abnormality of the distal phalanx of the thumb in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphysis located at the proximal end of the distal phalanx of the thumb.
A triangular appearance of the epiphysis of the proximal phalanx of the thumb of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the proximal phalanx of the thumb. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Abnormally small size of the epiphysis located at the proximal end of the proximal phalanx of the thumb with respect to age-dependent norms.
A pseudoepiphysis (which is a secondary ossification center distinct from the normal epiphysis) of the proximal phalanx of the thumb.
Sclerosis of the epiphysis of the proximal phalanx of the thumb, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphysis of the proximal phalanx of the thumb. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Epiphysis of the proximal phalanx of the thumb having multiple bony fragments.
Abnormally large size of the epiphysis located at the proximal end of the proximal phalanx of the thumb with respect to age-dependent norms. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
A cone-shaped appearance of the epiphysis of the middle phalanx of the thumb of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
An abnormality of the proximal phalanx of the thumb in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphysis located at the proximal end of the proximal phalanx of the thumb. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
This term applies if the epiphysis of the proximal phalanx of the thumb, which is located at the proximal end of the phalanx, does not appear in concordance with gender and age dependant norms as seen on x-rays. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
The absence of a phalangeal segment of a thumb.
Triangular shaped distal phalanx of the thumb. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
An uneven increase in bone density of the distal phalanx of the thumb.
A deviation from the normal straight shape of the distal phalanx of the thumb.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the distal phalanx of the thumb is affected.
Fusion of the proximal phalanx of the thumb with the 1st metacarpal.
Fusion of a phalanx of the thumb with another bone.
An uneven increase in bone density of the proximal phalanx of the thumb.
A deviation from the normal straight shape of the proximal phalanx of the thumb.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the proximal phalanx of the thumb is affected.
Increased width of the proximal phalanx of the thumb. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
This term applies if the proximal phalanx of the thumb is either small/hypoplastic or absent. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Chronic loss of joint motion of the carpometacarpal joint of the thumb due to structural changes in non-bony tissue. This joint is formed by the first metacarpal and the trapezial bone and is also called Articulatio carpometacarpalis pollicis, carpometacarpal articulation of thumb, carpometacarpal joint of thumb or first carpometacarpal articulation. Seldom referred to as thumb saddle joint.
Insertion of thumb at a more distal location than normal.
Complete duplication of the first metacarpal bone.
This term applies if the proximal phalanx of the thumb is partially duplicated. Depending on the severity, the appearance on x-ray can vary from a notched phalanx (the duplicated bone is almost completely fused with the phalanx) to a partially fused appearance of the two bones. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Complete duplication of the proximal phalanx of the thumb. On x-ray two separate bones appear side to side. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.
Fusion of the proximal phalanx of the 2nd finger with the 2nd metacarpal.
Absence of the proximal phalanx of the 2nd finger.
The presence of a peripheral schwannoma.
Fusion of the proximal phalanx of the 2nd finger with another bone.
Uneven (irregular) increase in bone density of the proximal phalanx of the second finger.
Curved appearance of the proximal phalanx of the 2nd finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the proximal phalanx of the 2nd finger is affected.
Fusion of the proximal and middle phalanges of the 2nd finger.
Triangular shaped middle phalanx of the 2nd finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Fusion of the middle phalanx of the 2nd finger with another bone.
Uneven (irregular) increase in bone density of the middle phalanx of the second finger.
Curved appearance of the middle phalanx of the 2nd finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the middle phalanx of the 2nd finger is affected.
Increased width of the middle phalanx of the second finger.
Triangular shaped distal phalanx of the 2nd finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Uneven (irregular) increase in bone density of the distal phalanx of the second finger.
Curved appearance of the distal phalanx of the 2nd finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the distal phalanx of the 2nd finger is affected.
Increased width of the distal phalanx of the 2nd finger.
An tongue-like extension of hair towards the cheeks.
The hairline refers to the outline of hair of the head. An abnormality of the hairline can refer to an unusually low or high border between areas of the scalp with and without hair or to abnormal projections of scalp hair.
A second finger with short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Chronic loss of joint motion of the metacarpophalangeal joint of the 2nd finger due to structural changes in non-bony tissue.
Chronic loss of joint motion of the distal interphalangeal joint of the 2nd finger due to structural changes in non-bony tissue.
A secondary ossification center in the proximal phalanx of the second finger that is distinct from the normal epiphysis that does not contribute to the longitudinal growth of a tubular bone.
A secondary ossification center in the middle phalanx of the second finger that is distinct from the normal epiphysis that does not contribute to the longitudinal growth of a tubular bone.
An abnormality of the middle phalanx of the second finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
A triangular appearance of the epiphysis of the distal phalanx of the 2nd finger of the hand. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the distal phalanx of the 2nd finger.
Abnormally small size of the epiphysis located at the proximal end of the distal phalanx of the 2nd finger with respect to age-dependent norms.
Irregular radiographic opacity of the epiphysis of the distal phalanx of the 2nd finger.
Fragmented appearance of the epiphysis of the distal phalanx of the 2nd finger.
Abnormally large size of the epiphysis located at the proximal end of the distal phalanx of the 2nd finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the distal phalanx of the 2nd finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
An abnormality of the distal phalanx of the second finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
A triangular appearance of the epiphyses of the 2nd finger of the hand.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the 2nd finger.
Abnormally small size of the epiphyses of the 2nd finger with respect to age-dependent norms.
Sclerosis of the epiphyses of the 2nd finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphyses of the 2nd finger.
Fragmented appearance of the epiphyses of the 2nd finger.
Abnormally large size of the epiphyses of the 2nd finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphyses of the 2nd finger of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
Absence of the epiphyses of the 2nd finger.
Displacement of the hand or of fingers of the hand from their normal position.
Fusion of the proximal phalanx of the 3rd finger with the 3rd metacarpal.
Fusion of the proximal and middle phalanges of the 3rd finger.
Fusion of the proximal phalanx of the 4th finger with the 4th metacarpal.
Fusion of the proximal and middle phalanges of the 4th finger.
Chronic loss of joint motion of the metacarpophalangeal joint of the 3rd finger due to structural changes in non-bony tissue.
Chronic loss of joint motion of the distal interphalangeal joint of the 3rd finger due to structural changes in non-bony tissue.
Displacement of the 3rd finger towards the radial side (i.e., towards the thumb).
Absence of the proximal phalanx of the 3rd finger.
Triangular shaped proximal phalanx of the 3rd (middle) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Fusion of the proximal phalanx of the 3rd finger with another bone.
Uneven (irregular) increase in bone density of the proximal phalanx of the third finger.
Dissolution or degeneration of bone tissue of the proximal phalanx of the 3rd finger.
Curved appearance of the proximal phalanx of the 3rd finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the proximal phalanx of the 3rd finger is affected.
Increased width of the proximal phalanx of the 3rd finger.
Triangular shaped phalanges of the 3rd finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Fusion of two or more bones of the 3rd finger.
Curved appearance of the phalanges of the 3rd finger.
A third finger with short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Triangular shaped middle phalanx of the 3rd (middle) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Fusion of the middle phalanx of the 3rd finger with another bone.
Uneven (irregular) increase in bone density of the middle phalanx of the third finger.
Dissolution or degeneration of bone tissue of the middle phalanx of the 3rd finger.
Curved appearance of the middle phalanx of the 3rd (middle) finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the middle phalanx of the 3rd finger is affected.
Absence of the distal phalanx of the middle (3rd) finger.
Curved appearance of the distal phalanx of the 3rd finger.
Triangular shaped distal phalanx of the 3rd (middle) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Uneven (irregular) increase in bone density of the distal phalanx of the third finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the distal phalanx of the 3rd finger is affected.
Increased width of the distal phalanx of the 3rd finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the 3rd finger.
Abnormally small size of the epiphyses of the 3rd finger with respect to age-dependent norms.
Sclerosis of the epiphyses of the 3rd finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphyses of the 3rd finger.
Fragmented appearance of the epiphyses of the 3rd finger.
Abnormally large size of the epiphyses of the 3rd finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphyses of the 3rd finger of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
An abnormality of the third finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphyses of the 3rd finger.
Triangular shaped phalanges of the 4th finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
A fourth finger with short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Increased width of the phalanges of the 4th finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the 4th finger.
Abnormally small size of the epiphyses of the 4th finger with respect to age-dependent norms.
Sclerosis of the epiphyses of the 4th finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphyses of the 4th finger.
Fragmented appearance of the epiphyses of the 4th finger.
Abnormally large size of the epiphyses of the 4th finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphyses of the 4th finger of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
An abnormality of the fourth finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of one or more epiphyses of the 4th finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphyses of the 5th finger.
Abnormally small size of the epiphyses of the 5th finger with respect to age-dependent norms.
Sclerosis of the epiphyses of the 5th finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphyses of the 5th finger.
Fragmented appearance of the epiphyses of the 5th finger.
Abnormally large size of the epiphyses of the 5th finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphyses of the 5th finger of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
An abnormality of the fifth finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of one or more epiphyses of the 5th finger.
Rhomboid or triangular shaped 5th (little) finger distal phalanx.
Triangular shaped phalanges of the 5th (little) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Aplasia/Hypoplasia of the phalanges of the 5th finger.
A fifth finger with short and wide phalanx that tapers distally. Bullet-shaped phalanges lack the normal diaphyseal constriction.
Increased width of the phalanges of the 5th finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the proximal phalanx of the 3rd finger.
Abnormally small size of the epiphysis located at the proximal end of the proximal phalanx of the 3rd finger with respect to age-dependent norms.
Sclerosis of the epiphysis of the proximal phalanx of the 3rd finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphysis of the proximal phalanx of the 3rd finger.
Fragmented appearance of the epiphysis of the proximal phalanx of the 3rd finger.
A cone-shaped appearance of the epiphysis of the proximal phalanx of the 3rd finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
An abnormality of the proximal phalanx of the third finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphysis located at the proximal end of the proximal phalanx of the 3rd finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the distal phalanx of the 3rd finger.
Abnormally small size of the epiphysis located at the proximal end of the distal phalanx of the 3rd finger with respect to age-dependent norms.
Sclerosis of the epiphysis of the distal phalanx of the 3rd finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphysis of the distal phalanx of the 3rd finger.
Fragmented appearance of the epiphysis of the distal phalanx of the 3rd finger.
Abnormally large size of the epiphysis located at the proximal end of the distal phalanx of the 3rd finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the distal phalanx of the 3rd finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
An abnormality of the distal phalanx of the third finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphysis located at the proximal end of the distal phalanx of the 3rd finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the middle phalanx of the 3rd finger.
Abnormally small size of the epiphysis located at the proximal end of the middle phalanx of the 3rd finger with respect to age-dependent norms.
Sclerosis of the epiphysis of the middle phalanx of the 3rd finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphysis of the middle phalanx of the 3rd finger.
Fragmented appearance of the epiphysis of the middle phalanx of the 3rd finger.
Abnormally large size of the epiphysis located at the proximal end of the middle phalanx of the 3rd finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the middle phalanx of the 3rd finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
An abnormality of the middle phalanx of the third finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphysis located at the proximal end of the middle phalanx of the 3rd finger.
Abnormality of one or all of the epiphyses of the proximal, middle, and distal phalanges of the 3rd finger.
A small/hypoplastic or absent/aplastic 3rd (middle) finger.
Triangular shaped proximal phalanx of the 4th (ring) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Fusion of the proximal phalanx of the 4th finger with another bone.
Uneven (irregular) increase in bone density of the proximal phalanx of the fourth finger.
Dissolution or degeneration of bone tissue of the proximal phalanx of the 4th finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the proximal phalanx of the 4th finger is affected.
Triangular shaped middle phalanx of the 4th (ring) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Fusion of the middle phalanx of the 4th finger with another bone.
Uneven (irregular) increase in bone density of the middle phalanx of the fourth finger.
Triangular shaped distal phalanx of the 4th (ring) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Uneven (irregular) increase in bone density of the distal phalanx of the fourth finger.
Dissolution or degeneration of bone tissue of the distal phalanx of the 4th finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the distal phalanx of the 4th finger is affected.
Absence of the proximal phalanx of the ring (4th) finger.
Dissolution or degeneration of bone tissue of the middle phalanx of the 4th finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the middle phalanx of the 4th finger is affected.
Increased width of the middle phalanx of the 4th finger.
Increased width of the distal phalanx of the 4th finger.
Absence of the distal phalanx of the ring (4th) finger.
Curved appearance of the middle phalanx of the 4th (ring) finger.
Curved appearance of the distal phalanx of the 4th (ring) finger.
Curved appearance of the phalanges of the 4th (ring) finger.
Displacement of the 4th finger towards the radial side (i.e., towards the thumb).
Displacement of the 4th finger towards the ulnar side (i.e., towards the ring finger).
Chronic loss of joint motion of the metacarpophalangeal joint of the 4th finger due to structural changes in non-bony tissue.
Chronic loss of joint motion of the distal interphalangeal joint of the 4th finger due to structural changes in non-bony tissue.
Displacement of the 4th finger from its normal position.
A small/hypoplastic or absent/aplastic 4th (ring) finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the proximal phalanx of the 4th finger.
Abnormally small size of the epiphysis located at the proximal end of the proximal phalanx of the 4th finger with respect to age-dependent norms.
Sclerosis of the epiphysis of the proximal phalanx of the ring finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphysis of the proximal phalanx of the 4th finger.
Fragmented appearance of the epiphysis of the proximal phalanx of the 4th finger.
Abnormally large size of the epiphysis located at the proximal end of the proximal phalanx of the 4th finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the proximal phalanx of the ring finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
Absence of the epiphysis located at the proximal end of the proximal phalanx of the 4th finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the distal phalanx of the 4th finger.
Abnormally small size of the epiphysis located at the proximal end of the distal phalanx of the 4th finger with respect to age-dependent norms.
Sclerosis of the epiphysis of the distal phalanx of the ring finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphysis of the distal phalanx of the 4th finger.
Fragmented appearance of the epiphysis of the distal phalanx of the 4th finger.
Abnormally large size of the epiphysis located at the proximal end of the distal phalanx of the 4th finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the distal phalanx of the ring finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
An abnormality of the distal phalanx of the fourth finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphysis located at the proximal end of the distal phalanx of the 4th finger.
Absence of the distal phalanx of the little (5th) finger.
Triangular shaped distal phalanx of the 5th (little) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Patchy increase in bone density of the distal phalanx of the 5th finger.
Dissolution or degeneration of bone tissue of the distal phalanx of the 5th finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the distal phalanx of the 5th finger is affected.
Increased width of the distal phalanx of the 5th finger.
Rhomboid or triangular shaped 5th (little) finger proximal phalanx.
Fusion of the proximal phalanx of the 5th finger with the 5th metacarpal.
Triangular shaped proximal phalanx of the 5th (little) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Fusion of the proximal phalanx of the 5th finger with another bone.
Patchy increase in bone density of the proximal phalanx of the 5th finger.
Dissolution or degeneration of bone tissue of the proximal phalanx of the 5th finger.
Curved appearance of the proximal phalanx of the 5th finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the proximal phalanx of the 5th finger is affected.
Absence of the proximal phalanx of the little (5th) finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the middle phalanx of the 4th finger.
Abnormally small size of the epiphysis located at the proximal end of the middle phalanx of the 4th finger with respect to age-dependent norms.
Sclerosis of the epiphysis of the middle phalanx of the ring finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphysis of the middle phalanx of the 4th finger.
Fragmented appearance of the epiphysis of the middle phalanx of the 4th finger.
Abnormally large size of the epiphysis located at the proximal end of the middle phalanx of the 4th finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the middle phalanx of the ring finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
An abnormality of the middle phalanx of the fourth finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphysis located at the proximal end of the middle phalanx of the 4th finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the middle phalanx of the 5th finger.
Abnormally small size of the epiphysis located at the proximal end of the middle phalanx of the 5th finger with respect to age-dependent norms.
Sclerosis of the epiphysis of the middle phalanx of the little finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphysis of the middle phalanx of the 5th finger.
Fragmented appearance of the epiphysis of the middle phalanx of the 5th finger.
Abnormally large size of the epiphysis located at the proximal end of the middle phalanx of the 5th finger with respect to age-dependent norms.
A cone-shaped appearance of the epiphysis of the middle phalanx of the little finger of the hand, producing a 'ball-in-a-socket' appearance. This epiphysis is located at the proximal end of the phalanx and is normally nearly flat. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of the phalanx.
An abnormality of the middle phalanx of the fifth finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Absence of the epiphysis located at the proximal end of the middle phalanx of the 5th finger.
Fragmented appearance of the epiphysis of the proximal phalanx of the 5th finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the proximal phalanx of the 5th finger.
Irregular radiographic opacity of the epiphysis of the proximal phalanx of the 5th finger.
An abnormality of the proximal phalanx of the fifth finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Abnormally small size of the epiphyses located at the distal end of the metacarpals in respect to age-dependent norms.
Absence or underdevelopment (hypoplasia) of the proximal phalanx of the little (5th) finger.
Sclerosis of the epiphyses of the metacarpals, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Irregular radiographic opacity of the epiphyses of the metacarpals.
Fragmented appearance of the epiphyses of the metacarpals.
An abnormality of the distal phalanx of the fifth finger in which the epiphysis surrounds a phalangeal bone, having a bracket-like form and reaching from the proximal side of a phalanx to the distal side.
Chronic loss of joint motion of the metacarpophalangeal joint of the 5th finger due to structural changes in non-bony tissue.
Chronic loss of joint motion of the distal interphalangeal joint of the 5th finger due to structural changes in non-bony tissue.
Triangular shaped middle phalanx of the 5th (little) finger. A triangular or so called delta shaped phalanx is a typical result after a bracket epiphysis of the affected phalanx.
Displacement of the 5th finger towards the ulnar side.
Fusion of the middle phalanx of the 5th finger with another bone.
Patchy increase in bone density of the middle phalanx of the 5th finger.
Abnormality of one or all of the epiphyses of the proximal, middle, and distal phalanges of the 4th finger.
Curved appearance of the middle phalanx of the 5th finger.
A triangular appearance of the epiphyses of the metacarpals. Thess epiphyses are located at the distal end of the metacarpals.
Dissolution or degeneration of bone tissue of the middle phalanx of the 5th finger.
Bullet-shaped phalanx refers to a short and wide phalanx that tapers distally . Bullet-shaped phalanges lack the normal diaphyseal constriction. This term is used if the middle phalanx of the 5th finger is affected.
Irregular radiographic opacity of the epiphysis of the distal phalanx of the 5th finger.
Fragmented appearance of the epiphysis of the distal phalanx of the 5th finger.
The presence of abnormal punctate (speckled, dot-like) calcifications in the epiphysis of the distal phalanx of the 5th finger.
Absence of the epiphysis located at the proximal end of the proximal phalanx of the 5th finger.
Abnormally small size of the epiphysis located at the proximal end of the proximal phalanx of the 5th finger with respect to age-dependent norms.
Abnormally large size of the epiphysis located at the proximal end of the proximal phalanx of the 5th finger with respect to age-dependent norms.
Sclerosis of the epiphysis of the proximal phalanx of the little finger, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays. [HPO:curators]
Abnormality of the epiphysis of the proximal phalanx of the fifth finger. This epiphysis is located on the proximal end of the phalanx.
Abnormality of one or all of the epiphyses of the proximal, middle, and distal phalanges of the 5th finger.
Abnormality of the proximal phalanx of the little (5th) finger.
Abnormally small size of the epiphysis located at the proximal end of the distal phalanx of the 5th finger with respect to age-dependent norms.
Abnormally large size of the epiphysis located at the proximal end of the distal phalanx of the 5th finger with respect to age-dependent norms.
An abnormal union between bones or parts of bones lower limbs.
A disease or lesion affecting the muscles of the thorax.
An increase in adipose tissue mass by hyperplastic growth (increase in the number of adipocytes) or by hypertrophic growth (increase in the size of adipocytes occurring primarily by lipid accumulation within the cell).
Absence (due to failure to form) or underdevelopment of bones of the axial skeleton.
An abnormality of the axial skeleton, which comprises the skull, the vertebral column, the ribs and the sternum. [HPO:probinson]
Absence or underdevelopment of a cranial sinus or sinuses.
Absence or underdevelopment of frontal sinus.
Absence or underdevelopment of the mandible.
Absence or underdevelopment of the Maxilla.
Absence (due to failure to form) or underdevelopment of one or more components of the skeleton.
Congenital absence of the left half of the diaphragm.
Abnormal ossification (bone tissue formation) affecting the pubic bone, also known as the pubis.
A type of malocclusion in which there is a gap between the anterior teeth (incisors).
Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.
Muscular atrophy involving the quadriceps muscle.
Generalized weakness of the muscles of the arms and legs.
Loss (reduction of previously present) of subcutaneous adipose tissue in the gluteal region.
Sudden and involuntary contractions of one or more muscles of the leg brought on by physical exertion.
Decreased activity of the mitochondrial respiratory chain. [HPO:probinson]
Muscular atrophy that does not display a progression in severity with time.
Muscle weakness affecting the tibialis anterior muscle.
Progressive muscular atrophy affecting muscles in the distal portions of the extremities.
A moderate degree of slow or limited growth after birth, being between three and four standard deviations below age- and sex-related norms.
Underdevelopment of the ischiopubic ramus, which is comprised of the inferior pubic ramus and the inferior ramus of the ischium.
The sacroiliac joint in the bony pelvis connects the sacrum and the ilium of the pelvis, which are joined by strong ligaments. The notch is located directly superior to the joint. This term refers to a increase in the lateral dimension of the notch.
Developmental acceleration of ossification of the proximal epiphysis of the femur.
Abnormally wide morphology of the proximal epiphysis of the femur.
Increased width of the proximal part of the shaft (metaphysis) of the femur.
Any structural abnormality of the renal artery.
Aplasia or developmental hypoplasia of the inner ear.
The presence of aplasia or developmental hypoplasia of all or part of the external ear.
The presence of aplasia or developmental hypoplasia of the ear.
The presence of a partially duplicated kidney.
Unusual gonadal development in a person with a 46,XY male karyotype, leading to a more female sex differentiation.
Deposition of calcium salts in gonadal tissue.
Presence of a single diverticulum (sac or pouch) in the wall of the urinary bladder.
Absence or developmental hypoplasia of the uterus.
The presence of many cysts in the medulla of the kidney.
Aplasia or developmental hypoplasia of the fallopian tube. [HPO:probinson]
Absence of sex glands (gonads are the organs that produce gametes; testis in males and ovary in females).
A form of sensorineural hearing impairment with onset after the acquisition of speech.
A condition in which the superior portion of the helix is folded over to a lesser degree than normal.
Complete lack of functioning of the vestibular apparatus.
Aplasia or developmental hypoplasia of the sacral bone.
The presence of a moderate form of sensorineural hearing impairment. [HPO:probinson]
A severe form of hypermetropia with over +5.00 diopters.
Early closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life.
Decreased ossification of the cervical vertebral bodies, i.e., of the Cervical vertebrae set.
Any abnormality of the atlas and the axis.
An abnormality of the shape of the lumbar vertebra L1 such that it is wedge-shaped (narrow towards the front).
The presence of punctiform calcification of the bone of the vertebral bodies.
Detachment of the distal fingernails from the nail bed.
A thickening of the stratum corneum, the outer layer of the skin, in the region surrounding the nails.
A nail of the fifth finger that is diminished in length and width, i.e., underdeveloped nail of little finger.
Chronic infection of the nails by Candida species.
An abnormality of the calcaneus, also known as the heel bone, one of the or heel bone, one of the components of the tarsus of the foot which make up the heel.
A neonatal decreased concentration of proteins in the blood.
Decreased activity of coagulation factor XIII (also known as fibrin stabilizing factor). Activated Factor XIII cross-links fibrin polymers solidifying the clot.
Reduced ability to transform factor X into its activated form factor Xa.
An abnormality of adhesion of thrombocytes. Normally, platelets adhere to collagen in the vascular subendothelium within seconds of injury via a receptor made up of glycoprotein Ia and IIa and GPVI and to vWF via receptor GPIb/IX/V. The adherent platelets then release granules that lead to platelet activation and aggregation.
Underdevelopment of the dilatator pupillae.
An increased concentration of a branched chain amino acid in the blood.
A partial reduction in level of the complement component Factor D in circulation.
Decreased activity of von Willebrand factor. Von Willebrand factor mediates the adhesion of platelets to the collagen exposed on endothelial cell surfaces.
Reduced activity of coagulation factor X. The extrinsic and intrinsic pathways converge at factor X (fX). The extrinsic pathway activates fX by means of d factor VII with its cofactor, tissue factor. The intrinsic pathway activates fX by means of the tenase complex (Ca2+ and factors VIIIa, IXa and X) on the surface of activated platelets. Factor Xa in turn activates prothrombin (factor II) to thrombin (factor IIa).
Abnormal response to collagen or collagen-mimetics as manifested by reduced or lacking aggregation of platelets upon addition collagen or collagen-mimetics.
An increased alkaline phosphatase activity measured within leukocytes.
A reduction in the activity of the mitochondrial respiratory chain complex II, which is part of the electron transport chain in mitochondria. [HPO:probinson]
Degeneration of the olivary bodies, prominent oval structures in the medulla oblongata.
A partial reduction in level of the complement component Factor H in circulation.
Atrophy (wasting) of the cerebellar cortex.
An abnormality of zinc ion homeostasis. [HPO:probinson]
Developmental hypoplasia of the adrenal medulla.
The presence of multiple pancreatic islet cell adenomas.
An abnormal reduction in the Arden ratio, which is the ratio between the light peak and the dark trough of the smoothed (physiologic) EOG record.
Reduced activity of coagulation factor VII. Factor VII is part of the extrinsic coagulation pathway, which is initiated at the site of injury in response to the release of tissue factor (fIII). Tissue factor and activated factor VII catalyze the activation of factor X.
Reduced proportion of helper T cells relative to the total number of T cells.
A decrease in alkaline phosphatase activity measured within leukocytes below detectable levels .
An increase in the level of 3-hydroxydicarboxylic acid in the urine.
Excessive amounts of mucopolysaccharide in the urine.
Abnormal response to epinephrine as manifested by reduced or lacking aggregation of platelets upon addition of epinephrine.
Delayed maturation and calcification of the calcaneus.
Synostosis of the calcaneus with the navicular bone.
Limitation of the ability to bend the toes.
An anomaly of the fifth metatarsal bone.
An abnormally high concentration of serum conjugated estriol as compared to normal values for gestational-age.
Virilization (deepening of voice, facial hirsutism and scalp hair loss) with onset during pregnancy (usually towards the end of the first trimester) and regression several months post-partum.
Absence or underdevelopment of the lens.
Absence or underdevelopment of the anterior segment of the eye.
Congenital absence or underdevelopment of the fovea centralis.
Absence or underdevelopment of the uvea, the pigmented middle layer of the eye consisting of the iris and ciliary body together with the choroid.
Any abnormality of the blood vessels of the conjunctiva.
Absence or underdevelopment of the iris.
An anomaly of the space between the medial and lateral canthi of the two open eyelids.
An abnormality of an extraocular muscle.
An arterial or venous retinal vascular anomaly.
Microscopic aneurysms of the retinal arterioles near the central part of the fundus, visible as small round dark red dots on the retinal surface (not arising from visible vessels) that are by definition less than the diameter of the major optic veins as they cross the optic disc.
Abnormality of macular or foveal pigmentation. [DDD:ncarter]
Congenital malformation of the lacrimal duct associated with incomplete development of the bony nasolacrimal canal or craniofacial anomalies.
Retinal exudate within the retinal tissue itself.
Decreased amount of pigmentation in the macula lutea.
Blockage of retinal arteriole, generally associated with interruption of blood flow and oxygen delivery to affected regions of the retina.
A spectrum of fundoscopic appearances characterized by the development of a variety of patterns of deposits predominantly in the macular area. The deposits are typically bilateral, relatively symmetrical, yellow/white and associated with changes at the level of the retinal pigment epithelium. With time, retinal atrophy may occur. A number of pattern dystrophy subtypes have been described including butterfly-shaped dystrophy, reticular dystrophy (net-like pattern) and fundus pulverulentus (granular, mottled pigmentation).
Chorioretinal atrophy concentrated around the optic papilla (i.e., the optic nerve head).
A type of posterior cortical cataract characterized by dense lenticular opacities.
A type of retinal reticular pigmentation that forms a polygonal, netlike arrangement of hyperpigmented lines forming geometric patterns in the fundus.
Congenital abnormal dilation of the pupil on both sides.
Separation of the inner layers of the retina (neural retina) from the pigment epithelium occuring near the outer limit (periphery) of the retina.
Anomaly of the visual evoked potentials elicited by a flash stimulus, generally a flash of light subtending an angle of at least 20 degrees of the visual field and presented in a dimly lit room.
A congenital defect resulting in absence of the lacrimal duct.
A type of of patterned retinal dystrophy that shows a reticular pattern of pigmentation.
Congenital absence of the extraocular muscles.
A shape created by an acute downward arching of the upper eyelid and upward arching of the lower eyelid, toward the medial canthus, which gives the outline of the palpebral fissures the configuration of an almond. Thus, the maximum distance between the fissures is offset from, and medial to, the center point.
Fibrosis of only some of the external ocular muscles such that the eyes of affected individuals are partially or completely fixed in a strabismic position.
Deposition of hyaline extracellular material (amyloid) into the vitreous humor, which can manifest as vitreous opacities and reduced visual acuity.
Increased length of the upper eyelashes.
Nonprogressive restriction of movement of the external ocular muscles such that the eyes of affected individuals are partially or completely fixed in a strabismic position. Residual eye movements are significantly limited.
Inability to see well at night or in poor light with onset in adulthood.
A supranuclear gaze palsy is an inability to look in a horizontal direction as a result of cerebral impairment. There is a loss of the voluntary aspect of eye movements, but, as the brainstem is still intact, all the reflex conjugate eye movements are normal.
A form of uveitis that is not associated with the formation of granulomas.
Mottled (spotted or blotched with different shades) pigmentary abnormality of the macula lutea.
Wasting (atrophy) of the retinal pigment epithelium present in small, isolated areas.
A type of retinal neovascularization that affects the posterior pole of the retina.
Abnormal development of the choroid and retina.
A chronic irritative conjunctivitis, which commonly presents with general irritation and redness of the eyes, with a burning, dry, or foreign-body sensation of the eyes.
Vitelliform maculopathy is a sharply demarcated lesion caused by the accumulation of material, often lipofuscin in the subretinal space underlying the macula.
A congenital defect of development characterized by absence of the lacrimal gland.
Congenital abnormality of the extraocular muscles.
Tractional retinal detachment at the periphery of the retina.
Naevus flammeus localised in the skin of the neck. This is one of the most common birthmarks and present in approximately 25% of all newborns.
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body because of decreased osmotic pressure of plasma (hypoproteinemia).
The presence of multiple subcutaneous lipoma that cause pain.
A form of atopic dermatitis with onset in adulthood characterized by atopic red face, chronic lichenified eczema on the trunk, subacute or psoriasiform dermatitis.
Seborrheic dermatitis that is not localized to any one particular region.
Lack of skin pigmentation (coloring) of the anterior chest.
Loss of hair in the occipital region of the scalp with congenital onset.
Tiny bumps of thickened skin (hyperkeratosis) on the palms of the hands.
Increased susceptibility to staphylococcal infections, as manifested by recurrent episodes of staphylococcal infections.
Keratinization of the bulbar conjunctiva near the limbus (corneoscleral junction), resulting in a raised spot. [HPO:probinson]
Lichenification affecting primarily flexural areas of the skin.
A type of blistering that affects the skin of the palms of the hands and the soles of the feet.
The presence of two to five cafe-au-lait macules.
Telangiectasia (that is, the presence of small dilated superficial blood vessels) of the oral mucosa.
Photosensitivity of the skin occurring early in life.
An abnormality of the choroid plexus, which is the area in the cerebral ventricles in which cerebrospinal fluid is produced by modified ependymal cells.
An abnormality of the septum pellucidum, which is a thin, triangular, vertical membrane separating the lateral ventricles of the brain.
The presence of atrophy (wasting) of the cerebrum, also known as the telencephalon, the largest and most highly developed part of the human brain.
Focal clonic seizures affecting one side of the face.
Nystagmus consisting of horizontal to-and-fro eye movements, in which the movement in one direction is faster than in the other.
A symmetric loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
Alternating and recurrent weakness of the external ocular muscles.
A reduction in the amplitude of sensory nerve action potential in distal nerve segments. This feature is measured by nerve conduction studies.
Muscular atrophy affecting the lower limb.
Presence of irregular redundant loops of focally folded myelin in a peripheral nerve.
Atherosclerosis (HP:0002621) of a cerebral artery.
A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hyperintensity affecting a particular region of the basal ganglia. [HPO:probinson]
Reduced amount of myelin in the nervous system resulting from defective myelinogenesis in the peripheral nervous system.
A complete lack of the ability to track objects with the ocular smooth pursuit system, a class of rather slow eye movements that minimizes retinal target motion.
A diffuse loss of myelin from nerve fibers in the central nervous system.
Stiffness of the limbs (acondition in which muscles cannot be moved quickly without accompanying pain or spasm) occurring in an asymmetric pattern.
Acute progressive areflexic weakness and mild sensory changes resulting from myelin breakdown and axonal degeneration.
A particular type of dementia characterized by a pattern of mental defects consisting prominently of forgetfulness, slowness of thought processes, and personality or mood change.
A loss of myelin from the internode regions along myelinated nerve fibers from segments of the peripheral nervous system.
An increase in size of the third ventricle.
A reduction in the amplitude of sensory nerve action potential. This feature is measured by nerve conduction studies.
Generalized atrophy or hypoplasia of the cerebrum.
A morphological abnormality of the metencephalon.
The formation of small cavities in the tissue of the basal ganglia.
A type of gliosis that occurs in the vicinity of injured neurons.
Proximal spinal muscular atrophy, i.e., muscular weakness and atrophy related to loss of the motor neurons of the spinal cord and brainstem.
The presence of developmental dysplasia of the cortex of frontal lobe and the cortex of parietal lobe.
A cerebral cortical malformation with features of unilateral excessive cortical folding and abnormal cortical layering. It comprises two sub-types depending on the areas affected: unilateral hemispheric and focal polymicrogyria.
Stiffness (a condition in which muscles cannot be moved quickly without accompanying pain or spasm) of the axial musculature.
Curvilinear intracellular accumulation of autofluorescent lipopigment storage material within axons. [HPO:probinson]
The presence of calcium deposition within brain structures that is present already at the time of birth.
A diffuse loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
A symmetric and progressive loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
The occurrence of repeated episodes of generalized muscular hypotonia.
The presence of a papillary adenocarcinoma of the ovary.
The presence of a carcinoma in the renal pelvis.
Absence or underdevelopment of the clavicles (collar bones).
An abnormality of the hepatic vasculature.
An abnormality of an atrioventricular valve.
Abnormally short chordae tendineae of the tricuspid valve.
Abnormal tortuous (i.e., twisted) form of the aorta.
A form of ventricular preexcitation due to the presence of multiple accessory pathways for cardiac conduction.
An abnormality of filling of a ventricle with blood during diastole.
Inflammation of the coronary arteries involving a granulomatous response, i.e., a non-specific inflammatory response involving granulomas, defined as a compact organized collection of mature mononuclear phagocytes including epithelioid and giant cells.
An abnormal morphology of the ribs consisting of shorted, abnormally curved ribs. On posteroanterior chest radiography, the ribs show a curvature resembling that of a coat hanger (clothes hanger).
Osteosclerosis of ribs (increased density related to increased bone mass).
An abnormally straight configuration of the clavicle, a tubular bone which normally is doubly curved .
An abnormal reduction in the number of mitochondria in hepatocytes.
An abnormal increase in the amount of intracellular lipid droplets in hepatocytes.
Decreased activity of complex II Of the mitochondrion in the liver.
A type of pulmonary sequestration that is completely enclosed in its own pleural sac, occurring above, within, or below the diaphragm, and without communication with the tracheobronchial tree.
An abnormality of the pulmonary lymphatic chain.
Absence (due to failure to form) or underdevelopment of the humerus.
Absence (due to failure to form) or underdevelopment of one or more forearm bones.
Absence or underdevelopment of the carpal bones.
An anomaly of a growth plate of a femur.
Absence (due to failure to form) or underdevelopment of the bones of the upper limbs.
Absence (due to failure to form) or underdevelopment of the bones of the lower limbs.
An abnormality of the islet of Langerhans, i.e., of the regions of the pancreas that contain its endocrine cells. These are the alpha cells, which produce glucagon, the beta cells, which produce insulin and amylin, the delta cells, which produce somatostatin, the PP cells, which produce pancreatic polypeptide, and the epsilon cells, which produce ghrelin.
Anomaly of the contour of the proximal epiphysis of the tibia such that its normally smooth appearance is irregular.
An anomaly of the metaphysis of the proximal femur (close to the hip).
Anomaly of the contour of the Distal epiphysis of femur such that its normally smooth appearance is irregular.
The femur is shortened and displays flaring (widening) of the metaphyses.
Increased width of the diaphysis of long bones.
Agenesis of lower secondary incisor or lower primary incisor.
Developmental hypoplasia of the tooth germ, i.e., of the structure that forms in odontogenesis that will develop into a tooth.
Lack of tooth eruption of the secondary dentition.
Obliteration of the pulp chambers owing to mineralization of the dental pulp.
An abnormality of morphology of the incisor tooth in which the tooth is shaped like a screwdriver blade, i.e., having a rhomboid shape.
An abnormality of morphology of primary molar.
Peg-shaped upper lateral secondary incisor tooth.
An abnormality of themorphology of secondary premolar tooth.
The presence of a supernumerary, i.e., extra, maxillary incisor, either the primary maxillary incisor or the permanent maxillary incisor.
Dagger-shaped calcifications in the dental pulp.
Agenesis of upper secondary incisor or of upper central primary incisor.
The presence of multiple embedded tooth germs which have failed to erupt.
A generalized form of developmental hypoplasia of the dental enamel.
Small/hypoplastic or absent/aplastic fingers.
A small/hypoplastic or absent/aplastic 2nd finger.
Abnormality of one or all of the epiphyses of the proximal, middle, and distal phalanges of the 2nd finger.
A small/hypoplastic or absent/aplastic 5th finger.
Decreased width of the metacarpal bones (that is, reduced diameter).
A reduction in diameter of the distal phalanx of finger towards the distal end such that the tip of the phalanx comes to a point (this feature can be observed on radiograms).
Presence of an additional phalanx-like bone, producing an extra, wedge-shaped bone at the base of the proximal phalanx of the second finger.
Alteration of the normally smooth radiographic contour of phalanges producing an irregular appearance.
The middle phalanx of finger resembles a thimble, a small metal cap to protect the finger while sewing that has a broad (proximal) base and narrower top, whereby both base and top are flat.
Phalanges of the fingers becoming thinner toward the distal end.
Irregular morphology of one or more metacarpal bones.
Increased length of multiple or a single phalanx of finger.
Increased side-to-side width of the metacarpal epiphyses.
Congenital hypoplasia of proximal phalanx of finger of all fingers. [HPO:probinson]
Increased length of the proximal phalanx of finger.
Metacarpal that becomes thinner toward the distal end.
Increased mobility of one ore more metacarpophalangeal joint.
Severely shortened metacarpal with a cuboidal appearance.
A reduction in phenylalanine 4-monooxygenase activity. [HPO:probinson]
A decreased concentration of arginine in the blood. [HPO:gcarletti]
Abnormal arrangement of the structures of the axoneme, which is the cytoskeletal structure that forms the inner core of the motile cilium and displays a canonical 9 + 2 microtubular pattern of motile cilia studded with dynein arms. [HPO:probinson, MP:0011050]
An abnormality of corticomedullary differentiation (CMD) on diagnostic imaging such as magnetic resonance imaging, computer tomography, or sonography. CMD is a difference in the visualization of cortex and medulla.
An anomaly of the outer shell (cortex) of a hand bone.
Any abnormality of the epiphyses of the phalanges or metacarpal bones.
Absence of a digit or of one or more phalanges of a finger.
A lack of bone mineralization of one or more body of cervical vertebra.
Fusion of a metacarpal bone with the proximal phalanx of the finger distal to it across the corresponding metacarpophalangeal joint.
An enchondroma is a benign growth of cartilage that develops within the medullary cavity of bone. Enchondromatosis refers to the presence of multiple enchondromas, and this term refers to the presence of multiple enchondromas within the medulla of metaphyseal bone. Radiographically an enchondroma presents a an oval, linear, or pyramidal osteolytic (radiolucent) lesion with well defined margins.
A form of triphalangeal thumb that can be placed opposite the fingers of the same hand.
Generalized deposition of calcium salts within the brain.
An abnormally round shape of the middle phalanx of the finger.
Abnormally short distal phalanx of toe of all toes.
Abnormal thickening of the cortex of the diaphyseal region of long bones.
A flattened vertebral body shape with reduced distance beween the vertebral endplates affecting the lumbar spine.
Bending or curvature of the distal phalanx of little finger in the radial direction (i.e., towards the 4th finger).
An abnormally small and flat configuration of the posterior cranial fossa.
An abnormal irregularity of cortical bone.
The ability of the thumb joints to move beyond their normal range of motion.
Abnormal reduction in length of all metacarpal bones.
A tongue-like protusion from the anterior aspect of lumbar vertebral bodies.
Deposition of calcium salts on both sides of the brain.
Extreme thickening of the cortex of long bones.
A foot deformity resulting due to an abnormality affecting the muscle and soft tissue. In contrast if the bones of the foot are affected the term structural foot deformity applies.
Multiple exostoses originating in the fingers and toes.
Sclerosis (abnormal hardening) of cortical bone, characterized by increased radiodensity.
A soft tissue continuity in the anteroposterior axis between the second to the fifth fingers that extends distally to at least the level of the proximal interphalangeal joints.
Underdevelopment of the ulna on both sides.
Bony fusion of the posterior part of the L5 vertebral body with the sacrum.
Osteoporosis affecting predominantly the vertebrae.
The ability of the interphalangeal joints to move beyond their normal range of motion.
Large hypermelanotic macules with jagged borders.
Loss of all scalp hair with congenital onset.
A type of proximal renal tubulopathy characterized by resorption defects leading to glycosuria, aminoaciduria, tubular proteinuria, renal hypophosphatemia, and urate tubular hyporeabsorption without bicarbonate loss.
Normal hemoglobin synthesis is characterized by production of equal amounts of alpha and beta globins. This term refers to a deviation from this pattern and is the main characteristic of the various forms of thalassemia.
An abnormality of the zygomatic arch, also known as the cheek bone.
The frontal suture divides the two halves of the frontal bone of the skull in infants and children and generally undergoes fusion by the age of six. A persistent frontal suture is referred to as a ""metopic suture"".
A form of lymphoid leukemia or lymphoma in which too many T-cell lymphoblasts are found in the blood, bone marrow, and tissues. Leukemia or lymphoma classification depends on which feature is more prominent.
A form of hemolytic anemia that can be triggered by exertion.
A type of T-cell lymphoma in which cancerous T-cells may present in the blood (leukemia), lymph nodes (lymphoma), skin or in multiple areas.
Increased megakaryocyte number, i.e., of platelet precursor cells, present in the bone marrow.
A reduction in the ability of neutrophils to kill the gram-positive bacteria, staphylococcus, which is commonly known as staph.
The frontal suture divides the two halves of the frontal bone in infants and usually fuses by the age of six years. The suture runs from the bregma (the point on the skull at which the coronal suture is intersected perpendicularly by the sagittal suture) to the nasion or nasal root. This term applies if the suture is widely patent from bregma to nasal root.
A deviation in any aspect of the alternative complement pathway.
Abnormally increased density of craniofacial bone tissue. [HPO:probinson]
An increased density in the cranial sutures following obliteration.
Increased susceptibility to systemic pyogenic infections, as manifested by recurrent episodes of systemic pyogenic infections.
Increased susceptibility to infection by gram-negative bacteria, as manifested by a medical history of repeated or frequent infections by these agents.
Persistent overgrowth of Candida albicans in the gastrointestinal tract. [HPO:probinson]
An abnormal reduction of the cell motility of neutrophils.
Increased susceptibility to protozoan infections, as manifested by recurrent episodes of protozoan infection.
Increased susceptibility to Haemophilus influenzae infections as manifested by recurrent episodes of infection by Haemophilus influenzae.
Increased susceptibility to herpesvirus, as manifested by recurrent episodes of herpesvirus.
A primary immune deficiency that is characterized by defects or deficiencies of T-lymphocytes that causes specific susceptibility to intracellular micro-organisms.
An abnormality of the structure of the veins that return deoxygenated blood from the body into the heart, i.e., the superior vena cava and the inferior vena cava.
Any structural abnormality of the carotid arteries, including the common carotid artery and its' arterial branches.
Abnormal bladder function (increased urge or frequency of urination or urge incontinence) resulting from abnormal functioning of the autonomic nervous system.
An abnormality of the complement system.
An abnormality of the gestures or movements executed with the facial muscles with which emotions such as fear, joy, sadness, surprise, and disgust can be expressed.
Formation of excess fibrous connective tissue in the tunica intima (innermost layer) of arteries in the pulmonary circulation.
A type of vasculitis (inflammation of blood vessel walls) affecting large arteries such as the aorta and branches of the aorta.
An abnormality of the jejunum, i.e., of the middle section of the small intestine.
Failure to form of portions of the abdominal musculature.
The presence of degenerative changes of the liver.
A form of chronic pancreatitis that is characterized by calcification.
Increased susceptibility to Giardia lamblia infection of the intestine, as manifested by a medical history of multiple episodes of Giardia lamblia intestinal infection.
Interphalangeal joint stiffness is a perceived sensation of tightness in the interphalangeal joints when attempting to move them after a period of inactivity.
A sensation of stiffness in the joints that occurs following waking up in the morning.
Abnormally flat shape of the heads of the metatarsal bones.
An impairment of the electrical continuity between the atria and ventricles.
Any structural abnormality of a cardiac atrium.
An abnormal localized widening (dilatation) of the abdominal aorta.
An abnormality of the intervertebral disk.
Any abnormality of the vertebral end plates, which are the top and bottom portions of the vertebral bodies that interface with the vertebral discs.
The presence of streaks (bands) of abnormally increased density of metaphyseal bone.
Developmental hypoplasia (shortening) of all phalanges of the foot.
The humerus is shortened and displays flaring (widening) of the metaphyses.
Absence or underdevelopment of the proximal epiphysis of the femur.
Coarctation of the aorta is a narrowing or constriction of a segment of the abdominal aorta.
Recurrent bleeding into the parenchyma of the brain.
Calcification, that is, pathological deposition of calcium salts in the tunica media of large (conduit) arteries.
An abnormal localized widening (dilatation) of the descending thoracic aorta.
A separation (dissection) of the layers of the extracranial portion of the internal carotid artery wall.
Increased pressure in the pre-hepatic portal vein.
Calcification, that is, pathological deposition of calcium salts, affecting arteries distributed throughout the body.
Arteriosclerosis (increased thickness, increased stiffness, loss of elasticity) of the small arteries of the brain.
Narrowing of peripheral arteries with reduction of blood flow to the limbs. This feature may be quantified as an ankle-brachial index of less than 0.9, and may be manifested clinically as claudication.
An abnormality of magnesium ion homeostasis. [HPO:probinson]
A form of lactic acidemia with congenital onset.
A form of lactic acidemia that occurs following exercise or exertion.
A form of lactic acidemia that occurs in relation to stress or infection.
Increased susceptibility to respiratory infections in early life, as manifested by recurrent episodes of respiratory infections.
Abnormal platelet response to ADP as manifested by reduced or lacking aggregation of platelets upon addition of ADP.
An abnormality of coagulation related to a decreased concentration of vitamin K-dependent protein S. Protein S is a cofactor of protein C. [HPO:probinson]
The presence of erythrocytes that are sphere-shaped and reduced in size.
Repeated episodes of obstruction of blood flow due to an embolus, i.e., blood clot that has traveled from its point of origin within the blood stream. [HPO:probinson]
A type of megaloblastic anemia that does not improve upon administration of folate. Since vitamin B12 acts by promoting recycling of folate, administration of vitamin B12 also does not improve this type of anemia.
An excessive division of the lobes of the nucleus of a neutrophil.
A form of hemolytic anemia that is triggered by ingestion of certain drugs.
Underdevelopment of the small intestine.
Fluid retention and edema in the intestine caused by a compromised lymphatic system.
The presence of multiple juvenile polyps in the stomach and intestine. The term juvenile polyps refer to a special histopathology and not the age of onset as the polyp might be diagnosed at all ages. The juvenile polyp has a spherical appearance and is microscopically characterized by overgrowth of an oedematous lamina propria with inflammatory cells and cystic glands. Juvenile polyps are a specific type of hamartomatous polyps.
Excessive, increased hair growth located in the elbow region.
A form of atrioventricular (AV) dissociation (i.e., the atria and the ventricles are under the control of two separate pacemakers) with congenital onset.
An abnormality of the normal developmental rotation of the kidney leading to an abnormal axial orientation of the kidney.
Fusion of the C5 and C6 cervical vertebrae.
Anterior tongue-like protrusions of thoracic vertebral bodies.
Increased size of the vertebral pedicle.
The closed form of spina bifida with incomplete closure of S1 with intact overlying skin.
Anterior tongue-like protrusions of the lower thoracic vertebral bodies.
The closed form of spina bifida with incomplete closure of the vertebra L5 with intact overlying skin.
Three ossification sites are present in typical vertebral bodies (C3-L5): a single ossification center in the vertebral body, and one each in the two neural arches. This term applies if there are additional vertebral ossification centers present during the development and maturation of the spine.
Excessive, increased hair growth located in the sacral region.
Reduced or lacking hair growth in the temporal region (i.e., around the temples on the side of the skull).
Bilateral absence (atresia) of the posterior nasal aperture (choana).
Stagnation of head growth seen as flattening of the head circumference curve.
Asymmetry of the bones of the skull and the face.
Hyperostosis (bony overgrowth) of the mandible. [HPO:probinson]
A rudimentary tag of ear tissue often containing a core of cartilage and located just in back of the auricle (outer part of the ear).
An abnormality of the cheek- one of two bilateral soft tissue facial structures in the region of the face inferior to the eyes and between the nose and the ear. ""Buccal"" means relating to the cheek. The cheek is part of the midface
An abnormality of alkaline phosphatase activity. [HPO:probinson]
Abnormality of glycosaminoglycan metabolism.
An abnormality of a glycoprotein metabolic process.
An abnormality of tryptophan metabolic process.
The presence of an abnormal concentration of nitrogen compounds.
An abnormality of calcium ion homeostasis.
An abnormality of the enteric nervous system, which comprises two types of ganglia, the myenteric (Auerbach's) and submucosal (Meissner's) plexuses. The enteric nervous system functions to control gut movement, fluid exchange between the gut and its lumen, and local blood flow.
An abnormal concentration of leptin in the blood.
Abnormality of a leucine metabolic process.
An abnormality of proteoglycan metabolism.
An abnormality of the metabolism of a carboxylic acid.
An abnormality of a pyrimidine base metabolic process.
Reduced function of the muscles required to generate subatmospheric pressure in the thoracic cavity during breathing: the diaphragm, the external intercostal and the interchondral part of the internal intercostal muscles.
An abnormality of glycosphingolipid metabolism.
An abnormality of a aromatic amino acid family metabolic process.
An abnormality of the anterior segment of the eyeball (which comprises the structures in front of the vitreous humour: the cornea, iris, ciliary body, and lens).
Any structural anomaly of the vitreous body.
An abnormal increase or decrease of weight or an abnormal distribution of mass in the body. [HPO:probinson]
Thickening of the left ventricle wall with congenital onset.
An abnormality of the gastric mucous membrane.
Abnormal formation of new bone on the surface of a bone of the hand.
Carpal bones with irregular or fragmented margins.
The bone-in-bone sign is a radiographic finding produced by increased sclerosis (abnormally dense bone) occurring intermittently with zones of relatively normal bone density. This term should be used to describe such a finding in the carpal bones.
A partial dislocation of the proximal interphalangeal joint of the little finger.
Abnormality of the epiphysis of the middle phalanx of the fifth finger. This epiphysis is located on the proximal end of the phalanx.
Curved phalanges of the 5th (little) finger.
Abnormality of the phalanges of the 5th (little) finger.
Osteolytic defects of the phalanges of the 4th (ring) finger. [HPO:curators]
This term groups together three conditions that presumably represent different degrees of severity of a midline defect of the nose or nasal tip.
An abnormal groove on the midline of the nose that may extend to the nasal tip.
Wrist is bent inward toward the thumb because of a congenital defect associated with shortening or absence of the radius.
A sloped configuration of the metaphysis (shaft) of the ulna.
The presence of a splayed (i.e.,flared) metaphyseal segment of the radius.
A premature fusion of the epiphyseal plates of the radius. Epiphyseal plates are located at the distal and proximal ends of the long bones, in this case of the radius and premature fusion will have an effect on the growh of the radial bone, inhibiting or at least disturbing the normal growth and development of the bone.
The distal epiphysis (rounded portion of bone at the far end of the radius distal to the growth plate) has an abnormal cone-shaped appearance.
Increased width of the ulna. [HPO:probinson]
A bending or abnormal curvature affecting either the radius, the ulna, or both.
A descriptive term for a forearm bone that appears to have an additional bone within it on radiography.
A delay in the process of formation and maturation of the epiphysis of one or more long bones that are part of the elbow.
An abnormal irregularity of the cortical surface of the diaphysis (shaft) of the humerus.
Ossification of the humeral epiphysis at an earlier age than normal. [HPO:probinson]
Destruction of an area of humerus bone due to a disease process, such as cancer.
Presence of more than one exostosis originating in one or noth humerus bones. An exostosis is a benign growth the projects outward from the bone surface. It is capped by cartilage, and arises from a bone that develops from cartilage.
An elevation in bone density in one or more diaphyses of the arms. Sclerosis is normally detected on a radiograph as an area of increased opacity.
A delay in the process of formation and maturation of the epiphysis of one or more long bones of the upper limbs.
Formation of calcified tissue in the soft tissues surrounding the shoulder.
Multiple small zones of sarcomeric disorganization and lack of oxidative activity (known as minicores) in type 1 and type 2 muscle fibers.
A body habitus that is tall, slim and underweight, with long legs and long arms (i.e., arm span exceeds height by 5 cm or more).
Congenital underdevelopment of lymph vessels.
The presence of abnormal muscle fiber size such that type 1 fibers are smaller than type 2 fibers.
Recurrent episodes of muscle flaccidity, a type of paralysis in which a muscle becomes soft and yields to passive stretching.
An abnormal, increased fatiguability of the musculature. [HPO:curators]
A type of genetic anticipation observed predominantly upon transmission from affected males.
Myotonia that occurs after a period of rest and decreases with continuing exercise.
Spontaneous, repetitive electrical activity demonstrated by electromyography (EMG). [HPO:probinson]
Absence of the epiphysis located at the proximal end of the distal phalanx of the 5th finger.
Lack of strength of the proximal musculature occuring late in the clinical course.
Muscular atrophy affecting the muscles of the pelvis.
An abnormal reduction in dihydropyrimidine dehydrogenase (NADP+) activity. [HPO:gcarletti]
Metachromasia (also known as metachromacy) is a characteristic color change which certain aniline dyes exhibit when bound to particular substances or when concentrated in solution. For example, the basic dye toluidine blue becomes distinctly pink when bound to cartilage matrix. In the sense used here, the metachromasia refers to a change in color not observed with normal tissues, anomalous staining with the cationic dyes toluidine blue O and Alcian blue resulting from excessive amounts of the polyanionic glycosaminoglycans.
An increased concentration of lactic acid in the urine.
An abnormal reduction in 4-hydroxyphenylpyruvate dioxygenase activity.
If positive, the ferric chloride test indicates an increased concentration of phenols in the urine or blood.
The presence of foam cells that contain lamellar inclusion bodies.
Lack of urothione (the urinary metabolite of molybdenum cofactor) in the urine.
An abnormally increased sodium concentration in the cytosol.
A positive response to the regitine blocking test consisting of a substantial reduction in blood pressure following administration of regitine, indicative of the presence of increased levels of epinephrine and norepinephrine in the circulation, which is seen in pheochromocytoma-associated hypertension.
Rhabdomyolysis induced by a viral infection.
Any abnormality of the soft tissues, including both connective tissue (tendons, ligaments, fascia, fibrous tissues, and fat).
An abnormally increased number of mitochondria in the cytoplasma adjacent to the sarcolemma (muscle cell membrane), whereby the mitochondria also possess an abnormal morphology.
Excretion of glycosaminoglycan in the urine. Glycosaminoglycans are long unbranched polysaccharides consisting of a repeating disaccharide unit.
An increased rate of iduronate-2-sulfatase activity in the blood. [HPO:probinson]
An abnormal reduction in xanthine dehydrogenase activity.
An increased concentration of ornithine in the urine.
An increased concentration of glutaric acid in the blood.
An increase in the reabsorption of calcium by the renal tubulus that is not associated with increased parathormone levels.
A reduction of the ratio of renal calcium clearance to creatinine clearance to below 0.01.
An elevated concentration of a gonadotropin hormone (stimulating hormone or luteinizing hormone) in the urine, consistent with the diagnosis of primary hypogonadism.
An abnormally increased diphosphate(4-) concentration in the urine. Diphosphate(4-), as ester with two phosphate groups, is also known as pyrophosphate.
Electromyographic (EMG) findings characteristic of axonal neuropathy, with normal or slightly decreased nerve conduction velocities, normal or slightly prolonged distal latencies, but significantly reduced motor potentials and sensory amplitudes. There may be spontaneous activity upon needle EMG studies, such as increased insertional activity, positive sharp waves, and fibrillation potentials.
Defective structure and function of myelin sheaths. Dysmyelination is distinguished from demyleination where there is destruction or damage of previously normal myelination.
Undetectable serum immunoglobulin A level at a value < 5 mg/dL (0.05 g/L).
A gammopathy in which there is a heterogeneous increase in IgM immunoglobulins.
An increased rate of premature chromosome condensation.
Evidence of chronic denervation on electromyography.
A reduction in the size of nerve terminals.
Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis. [HPO:probinson]
An anomaly of the atlantoaxial joint, i.e., of the joint between the first (atlas) and second (axis) cervical vertebrae.
Any abnormality of the neuromuscular junction, which is the synapse between the motor end plate of a motor neuron and the skeletal muscle fibers. [HPO:probinson]
Atrophic changes of axons of the peripheral nervous system.
An abnormality of the femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
An increased concentration of cystine within cells. This finding can be demonstrated on leukocytes, but is not specific to blood cells.
An increase in the number of chromosome sets per cell in bone marrow cells.
Normal peripheral blood lymphocytes, when stimulated by phytohemagglutinin (PHA) are cytotoxic for homologous and heterologous cells but not for autologous cells in monolayer culture. The cytotoxic effect is thought to be indicative of the immunological competence of the lymphocytes.
An increased concentration of noradrenaline in the urine.
An abnormality of the process of endochondral ossification, which is a type of replacement ossification in which bone tissue replaces cartilage.
An abnormal increase in catecholamine concentration in the blood.
Any anomaly in the composite material or the layered arrangement of the bony skeleton.
A increased concentration of arginine in the urine.
An abnormal decrease in orotidine 5'-phosphate decarboxylase activity. [HPO:gcarletti]
A decreased rate of pyruvate carboxylase activity.
The intracellular accumulation of autofluorescent storage material.
An abnormality of the spinocerebellar tracts, a set of axonal fibers originating in the spinal cord and terminating in the ipsilateral cerebellum. The spinocerebellar tract convey information to the cerebellum about limb and joint position (proprioception). They comprise the ventral spinocerebellar tract, the anterior spinocerebellar tract, and the posterior spinocerebellar tract.
An abnormality of the myelination of motor and sensory peripheral nerves. These are axons for motor nerves and dendrites for sensory nerves in the strict anatomic sense.
Reduced activity of coagulation factor VIII. Factor VIII (fVIII) is a cofactor in the intrinsic clotting cascade that is activated to fVIIIa in the presence of minute quantities of thrombin. fVIIIa acts as a receptor, for factors IXa and X. [HPO:probinson]
An abnormality in the of lipid metabolism. [HPO:probinson]
Overproduction of the hormone of cortisol by the adrenal cortex, resulting in a characteristic combination of clinical symptoms termed Cushing syndrome, with truncal obesity, a round, full face, striae atrophicae and acne, muscle weakness, and other features.
An abnormal concentration of a hormone in the blood.
The presence of an abnormal decrease or increase of one or more amino acids in the blood circulation.
Abnormality of the homeostasis (concentration) of a monoatomic ion. [HPO:probinson]
An abnormality of the composition of urine or the levels of its components.
An abnormality of the shoulder, which is defined as the structures surrounding the shoulder joint where the humerus attaches to the scapula.
An abnormality of the ulna bone of the forearm.
An anomaly of the calf bone (fibula), one of the two bones of the calf.
Absence or underdevelopment of tissue in the central nervous system.
Congenital absence of a part of the vermis of cerebellum.
An abnormal reduction in the concentration of corticotropin, also known as adrenocorticotropic hormone (ACTH), in the blood.
An abnormality of chromosome segregation.
Recurrent bouts of sudden, severe apnea that may be life-threatening.
Impaired production of memory cells, the B cells that persist for years or an entire lifetime and which confer rapid and enhanced response to secondary challenge.
Increased susceptibility to infections with Burkholderia cepacia, as manifested by recurrent episodes of infection with this agent.
An abnormality of the knee joint or surrounding structures.
A structural anomaly of the trachea. [HPO:probinson]
Any morphological abnormality of cartilage.
Increased susceptibility to enteroviral infections, as manifested by recurrent episodes of enteroviral infection.
Increased susceptibility to Serratia marcescens infections, as manifested by recurrent episodes of Serratia marcescens infection.
Underdevelopment of the lymph nodes. [HPO:probinson]
An increased susceptibility to abscess formation, as manifested by a medical history of recurrent abscesses.
An abnormality of the process of ossification of the skull.
An abnormality of the base of the skull, which forms the floor of the cranial cavity and separates the brain from other facial structures. The skull base is made up of five bones: the ethmoid, sphenoid, occipital, paired frontal, and paired parietal bones, and is subdivided into 3 regions: the anterior, middle, and posterior cranial fossae. The petro-occipital fissure subdivides the middle cranial fossa into 1 central component and 2 lateral components.
An abnormality of the frontal sinus, one of the mucosa-lined, normally air-filled paranasal sinuses of the bones of the skull. The frontal sinus is located within the frontal bone.
Abnormality of the calvaria, which is the roof of the skull formed by the frontal bone, parietal bones, and occipital bone.
The presence of an abnormal shape of the calvaria (skullcap), that is, of that part of the skull that is made up of the superior portions of the frontal bone, occipital bone, and parietal bones and covers the cranial cavity that contains the brain.
A type of hypertension associated with pheochromocytoma.
Abnormal outpouching or sac-like dilatation in an artery that originates from he abdominal aorta.
The aortic arch crosses the right mainstem bronchus and not the left mainstem bronchus, but does not result in the creation of a vascular ring. The first branch is the left brachiocephalic artery which divides into the left carotid artery and left subclavian artery, the second branch is the right carotid artery, the third branch is the right subclavian artery.
Developmental dysplasia of the hair. [HPO:probinson]
Impaired ability to repeat non-word sounds. Nonword repetition (NWR) is a measure of short-term phonological memory.
Deposition of calcium salts within small blood vessels of the brain.
Abnormality of the corticospinal tract, which is the chief element of the pyramidal system (the principle motor tract) and is the only direct connection between the cerebrum and the spinal cord. [HPO:probinson]
The presence, on T2-weighted magnetic resonance imaging, of markedly low signal intensity if the globus pallidus that surrounds a central region of high signal intensity in the anteromedial globus pallidus, producing an eye-of-the-tiger appearance.
Any structural anomal that affects the motor neuron. []
An abnormality of the caudate nucleus. [HPO:probinson]
Attacks of disabling daytime drowsiness and low alertness.
An abnormality of the autonomic nervous system.
An abnormality of the duodenum, i.e., the first section of the small intestine.
Loss of scalp hair at an earlier than normal age.
Defective development of the vermis of cerebellum.
Individuals with Pseudobulbar signs often also demonstrate abnormal behavioral symptoms such as inappropriate emotional outbursts of uncontrolled laughter or weeping etc.
An abnormality of the spinal cord (myelon). [HPO:probinson]
Any structural anomaly that affects the upper motor neuron.
An abnormality of the pulmonary pleura, the thin, transparent membrane which covers the lungs and lines the inside of the chest walls.
An abnormality of the upper respiratory tract.
Lipofuscin, a generic term applied to autofluorescent lipopigment, is a mixture of protein and lipid that accumulates in most aging cells, particularly those involved in high lipid turnover (e.g., the adrenal medulla) or phagocytosis of other cell types (e g., the retinal pigment epithelium or RPE; macrophage). This term pertains if there is an increase in the neuronal accumulation of lipofuscin (also known as autofluorescent lipoprotein) more than expected for the age of the patient. [HPO:probinson, pmid:11406682]
Venous or arterial thrombosis (formation of blood clots) of spontaneous nature and which cannot be fully explained by acquired risk (e.g. atherosclerosis).
An abnormality that involves the tubules and interstitial tissue of the kidney.
An abnormality of the mesangium, i.e., of the central part of the renal glomerulus between capillaries.
Any anomaly of the scalp, the skin an subcutaneous tissue of the head on which head hair grows.
Spontaneous detachment of a foot from the body.
Bending or curvature of a fifth toe in the tibial direction (i.e., towards the big toe).
Abnormalities of the metatarsal bones (i.e. of five tubular bones located between the tarsal bones of the hind- and mid-foot and the phalanges of the toes).
Congenital occlusion of a tube in the genital tract.
An abnormality of the morphology of the toes, such that the tips of the toes are prominent and bulbous.
An abnormality of the pancreas. [HPO:probinson]
Any structural anomaly of the tricuspid valve.
An abnormality of the pericardium, i.e., of the fluid filled sac that surrounds the heart and the proximal ends of the aorta, vena cava, and the pulmonary artery.
A structural anomaly of the muscle layer of the heart wall.
Any structural anomaly of the mitral valve.
Hypercortisolemia associated with a primary defect of the adrenal gland leading to overproduction of cortisol. [HPO:probinson]
An abnormality of the integument, which consists of the skin and the superficial fascia.
A morphological anomaly of the rib cage.
Absence or underdevelopment of the muscles of the upper arm.
Absence or underdevelopment of the musculature of the upper limbs.
Absence or underdevelopment of the muscles of the shoulder.
Absence or underdevelopment of the musculature.
Syndactyly with fusion of toes one to three.
A localized defect in the bone of the skull resulting from abnormal embryological development. The defect is covered by normal skin. In some cases, skull x-rays have shown underlying lytic bone lesions which have closed before the age of one year.
Head movements associated with nystagmus, that may represent an attempt to compensate for the involuntary eye movements and to improve vision.
Impairment of certain skills such as reading or writing, coordination, self-control, or attention that interfere with the ability to learn. The impairment is not related to a global deficiency of intelligence.
EEG shows spikes (<80 ms) and waves, which are recorded over the entire scalp and do not have a specific frequency.
Decreased length of the tubular bones of the hand, that is, the phalanges and metacarpals.
An abnormality of the fetus or the birth of the fetus, excluding structural abnormalities.
An abnormality of the placenta (the organ that connects the developing fetus to the uterine wall) or of the umbilical cord (the cord that connects the fetus to the placenta).
An abnormal hand position characterized by hyperextension of the fourth and fifth fingers at the metacarpophalangeal joints and flexion of the interphalangeal joints of the same fingers such that they are curled towards the palm.
Any abnormality of the size or morphology of the cornea.
Severe loss of visual acuity within hours or days. This is characteristic of Leber hereditary optic neuropathy.
Any structural abnormality of the fundus of the eye.
Jaundice that is sometimes present, sometimes not.
An abnormality of the dermatoglyphs, i.e., an abnormality of the patterns of ridges of the skin of palm of hand.
A type of pallor that is secondary to the presence of anemia.
An abnormality of one or more metaphysis, i.e., of the somewhat wider portion of a long bone that is adjacent to the epiphyseal growth plate and grows during childhood.
The bones of the skeleton undergo a series of characteristic changes in size, shape, and calcification from fetal life until puberty. An abnormality of this process can include delayed or accelerated skeletal maturation, or deviation of some, but not all bones from the expected patterns of maturation.
Abnormality of the pituitary gland (also known as hypophysis), which is an endocrine gland that protrudes from the bottom of the hypothalamus at the base of the brain. The pituitary gland secretes the hormones ACTH, TSH, PRL, GH, endorphins, FSH, LH, oxytocin, and antidiuretic hormone. The secretion of hormones from the anterior pituitary is under the strict control of hypothalamic hormones, and the posterior pituitary is essentially an extension of the hypothalamus, so that hypothalamus and pituitary gland may be regarded as a functional unit.
A condition of reduced function of the anterior pituitary gland characterized by decreased secretion of one or more of the pituitary hormones growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, prolactin, luteinizing hormone, and follicle-stimulating hormone.
An abnormality of the parathyroid gland. [HPO:curators]
An anomaly of the adnexa, uterus, and vagina (in female) or seminal tract and prostate (in male).
An abnormality of the urethra, i.e., of the tube which connects the urinary bladder to the outside of the body.
The presence of immunoglobulin A deposits in the glomerulus.
Any abnormality of the scapula, also known as the shoulder blade.
Progressive deterioration of peripheral axons.
An abnormality of the peripheral nervous system, which is composed of the nerves that lead to or branch off from the central nervous system. This includes the cranial nerves (olfactory and optic nerves are technically part of the central nervous system).
An abnormality of the nasolacrimal drainage system, which serves as a conduit for tear flow from the external eye to the nasal cavity.
Any structural abnormality of the choroid. [HPO:probinson]
An abnormality of the region situated around the orbit of the eye.
An anomaly of the pharynx, i.e., of the tubular structure extending from the base of the skull superiorly to the esophageal inlet inferiorly.
An anomaly in the placement or shape of the hairline (trichion) on the forehead, that is, the border between skin on the forehead that has head hair and that does not.
An abnormality of eye movement characterized by impairment of fast (saccadic) eye movements. [HPO:probinson]
An abnormality of the uvea, the vascular layer of the eyeball.
An abnormality in the process of focusing of light by the eye in order to produce a sharp image on the retina.
An abnormality of the choroid and retina.
An abnormality of the iris, which is the pigmented muscular tissue between the cornea and the lens, that is perforated by an opening called the pupil.
Abnormality of eyesight (visual perception).
An abnormality of the fovea centralis, the central area of the macula that mediates central, high resolution vision and contains the largest concentration of cone cells in the retina.
An increased amount of subcutaneous fat tissue around the neck.
Abnormality of the choanae (the posterior nasal apertures).
The cochlea is lacking the entire modiolus and cribriform area, resulting in a cystic appearance. This is accompanied by a large cystic vestibule. [HPO:probinson]
An abnormality of the sensory perception of sound.
An abnormality of the Maxilla (upper jaw bone).
An abnormality of the chin, i.e., of the inferior portion of the face lying inferior to the lower lip and including the central prominence of the lower jaw.
An anomaly of a muscle that is innervated by the facial nerve (the seventh cranial nerve).
An increased amount of subcutaneous fat tissue in the face.
Any abnormality of the mandible, the bone of the lower jaw.
An abnormality of the mastoid process, which is the conical prominence projecting from the undersurface of the mastoid portion of the temporal bone.
Abnormality of the paranasal (cranial) sinuses, which are air-filled spaces that are located within the bones of the skull and face and communicate with the nasal cavity. They comprise the maxillary sinuses, the frontal sinuses, the ethmoid sinuses, and the sphenoid sinuses.
Any abnormality of the size of the skull.
An abnormality of the anterior fontanelle, i.e., the cranial fontanelle that is located at the intersection of the coronal and sagittal sutures.
Any abnormality of the fontanelles (the regions covered by a thick membrane that normally ossify in the first two years of life) or the cranial sutures (the fibrous joints in which the articulating bones or cartilages of the skull are connected by sutural ligaments ).
Presence of telangiectases in the oral cavity. [HPO:probinson]
Telangiectasia (that is, the presence of small dilated superficial blood vessels) of the tongue.
Any abnormality of the parotid glands, which are the salivary glands that are located in the subcutaneous tissues of the face overlying the mandibular ramus and anterior and inferior to the external ear.
An abnormality of the lingual frenulum, that is of the small fold of mucous membrane that attaches the tongue to the floor of the mouth, or the presence of accessory frenula in the oral cavity.
Abnormality of the uvula, the conic projection from the posterior edge of the middle of the soft palate.
Abnormality of the oral cavity, i.e., the opening or hollow part of the mouth.
An abnormality of the ovulation cycle. [HPO:probinson]
Congenital anomaly characterized by closure or failure to develop an opening in the urethra in females.
Ambiguous genitalia in an individual with XX genetic gender. [HPO:probinson]
An anomaly of the labia, the externally visible portions of the vulva.
Congenital anomaly characterized by closure or failure to develop an opening in the urethra in males.
An abnormality of male external genitalia.
An abnormality of the male internal genitalia.
An abnormality of the female internal genitalia.
Deviation from the norm of height with respect to that which is expected according to age and gender norms.
An orally available combination formulation containing netupitant, a selective neurokinin 1 (NK1) receptor antagonist, and the hydrochloride salt form of palonosetron, a selective serotonin (5-hydroxytryptamine; 5-HT) receptor subtype 3 (5-HT3) antagonist, with antiemetic activity. Upon oral administration, palonosetron competitively blocks the action of 5-HT at 5-HT3 receptors located on vagal afferent nerves in the chemoreceptor trigger zone (CTZ). This inhibits acute emesis associated with 5-HT secretion and subsequent 5-HT3 activation. Netupitant competitively binds to and blocks the activity of the human NK1 receptors in the central nervous system (CNS), thereby inhibiting NK1 receptor binding of the endogenous tachykinin neuropeptide substance P (SP). This prevents delayed emesis, which is associated with SP secretion. Altogether, this results in the prevention of chemotherapy-induced nausea and vomiting (CINV).
An indication that no complication occurred.
The modulus of elasticity of the liver, representing the resistance of the liver to deformation. Liver stiffness has been shown to be a surrogate marker of advanced fibrosis and cirrhosis. Liver stiffness, measured by transient elastography, is an independent predictor of liver failure, hepatocellular carcinoma, and mortality in cirrhotic patients coinfected with the human immunodeficiency virus or acquired immune deficiency syndrome, and hepatitis C virus.
A response indicating that an individual has stopped trying, or knew they could not do this activity because of their shortness of breath.
A response indicating that something is a lot better.
A response indicating that something is a lot worse.
A response indicating that an individual has not done an activity for some reason not listed.
A response indicating a moderate level of confidence.
A tongue position where the tongue is pulled back in the mouth altering the shape of the sublingual space.
A measure of the slope of the occlusal plane on the right to the Frankfort horizontal in degrees, related to tooth eruption.
A horizontal streak found on the inner surface of the cheek at the level of the biting plane. It usually extends from the commissure to the posterior teeth and can extend to the inner lip mucosa and corners of the mouth. It is a common finding and most likely associated with pressure, frictional irritation, or sucking trauma from the facial surfaces of the teeth.
Hyperplastic epithelial cells with nodular distribution.
Disorder characterised by persistent airflow limitation with several features usually associated with asthma and several features usually associated with COPD; identified by the features that it shares with both asthma and COPD.
Abnormally flat (obtuse) angle of the mandible. The angle of the mandibular, located at the junction between the body and the ramus of the mandible, is normally close to being a right angle. This terms describes an abnormal increase of this angle such that the mandible appears flatter than normal.
A flat mandibular plane angle correlates with short anterior facial vertical dimensions (height) and anterior deep bite malocclusion.
A benign vasoproliferative lesion in which lymph node sinuses become converted to anastomosing endothelial-lined channels.
Chemical, biochemical and/or electrochemical actions causing the degradation of the hard tissue of the tooth.
The upper canine is positioned distally to the embrasure between the lower canine and first premolar, the canine occlusion is called Class III.
Confirmatory presence of bacterial microorganisms.
A measure of the slope of the occlusal plane on the left to the Frankfort horizontal in degrees, related to tooth eruption.
The surface is not intact with visible breakdown (hole) and extensive loss of mineral, extensive localised demineralisation where there is observable localised breakdown or distinct cavity (hole).
Carious lesion of interproximal origin arising on any approximal smooth surface of the tooth contacting an adjacent tooth.
Residual alveolar bone height of 11-15mm measured at the least vertical height of the mandible.
The edentulous span is confined to a single arch.
Unusually large or small tooth with abnormalities of the crown form or root configuration.
The upper canine is positioned mesial to the embrasure between the lower canine and first premolar, the canine occlusion is called Class II.
The surface remains intact with visible change, loss of mineral, localised demineralisation where there is no observable localised breakdown or distinct cavity (hole).
Past history of artificial enlargement of breast due to choice.
Position and activity of the tongue that can effect the stability and retention of a mandibular complete denture.
Extreme cant to the condylar head beyond the usual normal range.
The form and arrangement of the occlusal contacts in natural and artificial dentition.
Palatal vault morphology that does not resist vertical or horizontal movement of the denture base.
Upper respiratory tract infection symptoms include: laryngitis, pharyngitis, nasal congestion, rhinorrhea, sneezing and coryza.
Migraine is due to low estrogen level during the contraceptive pill-free interval.
Edentulous areas are found in both arches and the physiologic abutment support is compromised.
Arrested carious lesion that is not advancing.
The distance between the angle of the throat and soft tissue menton greater than 51mm+/-6mm.
No significant morphology affecting the coronal morphology of the teeth.
Angle formed by the junction of the posterior and lower borders of the lower jaw is above average.
Finding of shortened, hypertonic pelvic floor musculature
Undesirable contact of opposing occlusal surfaces on the nonworking side.
Hamular notch is well defined to establish the posterior extension of the denture base.
Pathology that affects the coronal morphology of 4 or more teeth in all sextants.
Pathology that affects the coronal morphology of three or less teeth in a sextant.
Angle formed by the junction of the posterior and lower borders of the lower jaw is below average.
A rare histopathological disorder of unknown aetiology characterised by the deposition of a subepithelial collagen band with accompanying inflammatory infiltrate.
Condition where roots of adjacent teeth approximate each other resulting in minimal bone between teeth.
Any posterior maxillary or mandibular span that is greater than 3 missing teeth or 2 molars; any edentulous span including anterior and posterior areas of 3 or more missing teeth.
The shape of ridge following loss of teeth; the residual ridge morphology is the most objective criteria for the maxilla on examination of the oral cavity since measurement of the residual bone height by radiography is not reliable.
The distance between the angle of the throat and soft tissue menton less than 51mm+/-6mm.
Hyperplastic, mobile anterior ridge that offers minimum support and stability of the denture base.
Dental caries involving a discrete area of tooth not including an existing restoration.
Palatal vault morphology that offers minimal resistance to vertical and horizontal movement of the denture base.
Carious lesion of pit and fissure origin in occlusal areas and buccal or lingual pits.
Residual bone height of 21mm or greater measured at the least vertical height of the mandible.
For the permanent dentition having 32 teeth. For the primary dentition having 20 teeth.
Woody tongue includes the involvement of the sublingual space causing elevation, posterior enlargement and protrusion of the tongue.
Residual bone height of 16-20mm measured at the least vertical height of the mandible.
A rare autosomal recessive inherited disorder caused by mutations in the SERAC1 gene. Multiple body systems are affected with manifestations including 3-methylglutaconic aciduria, deafness, encephalopathy and Leigh-like disease.
A lesion as a result of galvanic current in the oral cavity due to the presence of two or more dissimilar metals in dental restorations that are bathed in saliva, or a single metal restoration and two electrolytes, saliva and pulp tissue fluid, thus producing an electrolytic cell and an electric current. When such restorations touch each other, the current may be high enough to irritate the dental pulp and cause sharp pain. The anodic restoration or areas of a restoration are subject to electrolytic corrosion.
Characterised by spillage of melanin from the basal keratinocytes into the underlying connective tissue of the lips.
Mobile removable partial denture in the vertical direction.
Residual vertical bone height of 10mm or less measured at the least vertical height of the mandible.
A less aggressive and self-limited pathologic process that can develop without any obvious eliciting factor and is characterised by exposed necrotic bone involving the lingual mandible approximately at the level of the mylohyoid ridge.
A disorder characterised by a decline primarily in intellectual function due to disease of the brain caused by a variety of acquired conditions such as cerebrovascular disease, Alzheimer's disease, infections, adverse drug reactions and trauma.
Decreased or absent display of maxillary and/or the mandibular incisal edge at rest.
Loss of access hole filling material in screw-retained implants.
A finding of mandible bone height in edentulous patients by examination of the oral cavity in prosthodontics; part of prosthodontic classification in assessment for dentures/devices.
The edentulous span is confined to a single arch and one of the following: Any anterior maxillary span that does not exceed 2 missing incisors; any anterior mandibular span that does not exceed 4 missing incisors; or any posterior maxillary or mandibular span that does not exceed 2 premolars or 1 premolar and 1 molar.
Pathology that affects the coronal morphology of 4 or more teeth in three or more sextants.
A distal placement of the mandibular molar, a mesial relationship of the maxillary, or a combination of the two. The mesiobuccal cusp of the maxillary first molar occludes mesial to the buccal groove of the mandibular first molar, usually near the embrasure between the mandibular molar and second premolar. Subdivision of any malocclusion category denotes a unilateral malocclusion classification.
The edentulous span is in both arches and one of the following: Any anterior maxillary span that does not exceed 2 missing incisors; any anterior mandibular span that does not exceed 4 missing incisors; any posterior maxillary or mandibular span that does not exceed 2 premolars or 1 premolar and 1 molar; or the maxillary or mandibular canine is missing.
Decreased display of the maxillary incisal during a posed smile. Normal display should involve the whole maxillary incisors and interdental gingiva.
Increased display of maxillary and/or mandibular incisal edge when the jaws are at rest. This translates to >1.91 mm for men and 3.40 mm in women for the maxilla; and >1.23 mm for men and 0.49 mm in women for the mandible.
The upper canine is positioned in the embrasure between the lower canine and first premolar, the canine occlusion is called Class I.
Congenital nonprogressive cone-rod synaptic disorder is characterized by stable low vision, nystagmus, photophobia, a normal or near-normal fundus appearance, and no night blindness. Electroretinography shows an electronegative waveform response to scotopic bright flash, near-normal to subnormal rod function, and delayed and/or decreased to nonrecordable cone responses (Traboulsi, 2013; Khan, 2014).
A radioconjugate consisting of consisting of the high affinity somatostatin analogue iodo-tyrosine-3-octreotate (HA-TATE), labeled with the positron emission tomography (PET) tracer gallium Ga 68 via the macrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra-acetic acid (DOTA), which may be used as a human somatostatin receptor (SSTR) imaging agent in conjunction with PET to image neuroendocrine tumors (NETs). Gallium Ga 68-HA-DOTATATE binds to SSTRs, with high affinity for SSTR2, present on the cell membranes of many types of NETs. This allows for visualization of SSTR-positive cells upon imaging. SSTRs have been shown to be present in large numbers on NETs and their metastases, while most other normal tissues express low levels of SSTRs. HA-TATE is an octreotide derivative in which phenylalanine at position 3 is substituted with iodo-tyrosine and threoninol at position 8 is replaced by threonine. The iodo addition in Gallium Ga 68-HA-DOTA-TATE may allow for higher affinity for the SSTRs when compared to gallium Ga 68-DOTA-TATE.
A fully human monoclonal antibody directed against the human epidermal growth factor receptor ErbB3 (Her3) with potential antineoplastic activity. Seribantumab binds to and inhibits ErbB3 activation, which may result in inhibition of ErbB3-dependent PI3K/Akt signaling and so inhibition of cellular proliferation and differentiation. ErbB3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in solid tumors, including breast, lung, and colorectal tumors of epithelial origin; it has no active kinase domain itself but is activated through heterodimerization with other members of the EGFR receptor family that do.
Postoperative morbidity in patients recovering from general anesthesia where a depressed neuromuscular response due to residual PARESIS continues beyond a defined ANESTHESIA RECOVERY PERIOD.
A group of disorders characterized by physiological and psychological disturbances in appetite or food intake.
Tumors or cancer found specifically in the human left BREAST.
Tumors or cancer found specifically in the human right BREAST.
A pharmaceutical preparation of budesonide and formoterol fumarate that is used as an ANTI-ASTHMATIC AGENT and for the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE.
A pharmaceutical preparation of emtricitabine and tenofovir that is used as an ANTI-HIV AGENT in the treatment and prevention of HIV INFECTIONS.
Persistent detrimental effects from treatment for a condition. Included are effects from surgery such as POSTOPERATIVE COMPLICATIONS, and from DRUG THERAPY, such as CHEMICALLY INDUCED DISORDERS, or other THERAPEUTICS. Failure to attain a desired outcome from treatment for the condition is not considered an adverse effect.
Congenital anomaly in which both kidneys are located on the same side often fused.
A pharmaceutical preparation of sitagliptin phosphate and metformin hydrochloride that is used in the treatment of TYPE 2 DIABETES.
Drugs used to induce SLEEP, prevent SLEEPLESSNESS, or treat SLEEP INITIATION AND MAINTENANCE DISORDERS.
A pharmaceutical preparation of mometasone furoate and formoterol fumarate that is used as an inhaled dosage form for the treatment of ASTHMA.
A pharmaceutical preparation that contains emtricitabine, rilpivirine and tenofovir disoproxil fumarate. It is used to treat HIV INFECTIONS.
A pharmaceutical preparation of brimonidine tartrate and timolol maleate. The combined ADRENERGIC ALPHA2 RECEPTOR AGONIST and ADRENERGIC BETA-ANTAGONIST activity of these drugs reduce INTRAOCULAR PRESSURE in GLAUCOMA patients.
Emotional distress caused by repeated or prolonged expression of compassion or empathy. It may occur in individuals working in care giving professions.
A sub-PHENOTYPE of obese individuals who have a risk for CARDIOVASCULAR DISEASES between that of healthy individuals with normal weight and unhealthy individuals with obesity.
A transient exacerbation of symptoms of an existing disease or condition.
Abnormal sleep-wake schedule or pattern associated with the CIRCADIAN RHYTHM which affect the length, timing, and/or rigidity of the sleep-wake cycle relative to the day-night cycle.
A malignant neoplasm of epithelial cells of the SALIVARY GLANDS, with microcystic architecture, low-grade nuclei, and granular vacuolated cytoplasm.
These disorders are related to both SCHIZOPHRENIA SPECTRUM AND RELATED DISORDERS and DEPRESSIVE DISORDERS in terms of symptomatology, family history, and genetics. (DSM-V) .
Disorders in which exposure to a traumatic or stressful event is explicitly a diagnostic criterion.
Diagnosed when there are specific deficits in an individual's ability to perceive or process information efficiently and accurately. This disorder first manifests during the years of formal schooling and is characterized by persistent and impairing difficulties with learning foundational academic skills in reading, writing, and/or math. The individual's performance of the affected academic skills is well below average for age, or acceptable performance levels are achieved only with extraordinary effort. Specific learning disorder may occur in individuals identified as intellectually gifted and manifest only when the learning demands or assessment procedures (e.g., timed tests) pose barriers that cannot be overcome by their innate intelligence and compensatory strategies. For all individuals, specific learning disorder can produce lifelong impairments in activities dependent on the skills, including occupational performance. (from DSM-V)
Acute form of MALNUTRITION which usually affects children, characterized by a very low weight for height (below -3z scores of the median World Health Organization standards), visible severe wasting, or occurrence of nutritional EDEMA. It can be a direct or indirect cause of fatality in children suffering from DIARRHEA and PNEUMONIA. Do not confuse with starvation, a condition in which the body is not getting enough food, usually for extended periods of time.
An orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) with potential antineoplastic activity. Talazoparib selectively binds to PARP and prevents PARP-mediated DNA repair of single strand DNA breaks via the base-excision repair pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability and eventually leads to apoptosis. PARP catalyzes post-translational ADP-ribosylation of nuclear proteins that signal and recruit other proteins to repair damaged DNA and is activated by single-strand DNA breaks.
An orally bioavailable, Bcr-Abl tyrosine kinase inhibitor, with potential antineoplastic activity. Designed to overcome resistance of tumor cells to second generation Bcr-Abl inhibitors, PF-114 targets and binds to the Bcr-Abl fusion oncoprotein, including those fusion proteins with the 'gatekeeper' resistance mutation T315I, an amino acid substitution at position 315 in Bcr-Abl from a threonine (T) to an isoleucine (I). This inhibits Bcr-Abl-mediated proliferation of, and enhances apoptosis in, Philadelphia chromosome-positive (Ph+) hematologic malignancies. The Bcr-Abl fusion protein is an aberrantly activated tyrosine kinase produced by leukemia cells that contain the Philadelphia chromosome.
An orally bioavailable, small-molecule receptor tyrosine kinase inhibitor with potential antineoplastic activity. c-Met inhibitor JNJ-38877605 selectively inhibits c-Met, a receptor tyrosine kinase (RTK) involved in cancer cell survival and invasiveness, and tumor angiogenesis. c-Met is also known as hepatocyte growth factor receptor (HGFR).
A specific inhibitor of heat shock protein 90 (Hsp90) subtypes alpha and beta, with potential antineoplastic and chemo/radiosensitizing activities. Upon oral administration, Hsp90alpha/beta inhibitor TAS-116 specifically binds to and inhibits the activity of Hsp90 alpha and beta; this results in the proteasomal degradation of oncogenic client proteins, which inhibits client protein dependent-signaling, induces apoptosis, and inhibits the proliferation of cells overexpressing HSP90alpha/beta. Hsp90, a family of molecular chaperone proteins that are upregulated in a variety of tumor cells, plays a key role in the conformational maturation, stability, and function of ""client"" proteins within the cell,; many of which are involved in signal transduction, cell cycle regulation and apoptosis, including kinases, cell-cycle regulators, transcription factors and hormone receptors. As TAS-116 selectively inhibits cytosolic HSP90alpha and beta only and does not inhibit HSP90 paralogs, such as endoplasmic reticulum GRP94 or mitochondrial TRAP1, this agent may have less off-target toxicity as compared to non-selective HSP90 inhibitors.
An orally bioavailable inhibitor of Janus kinases 1 and 2 (JAK1/2), with potential anti-inflammatory, immunomodulating and antineoplastic activities. Upon administration, baricitinib binds to JAK1/2, which inhibits JAK1/2 activation and leads to the inhibition of the JAK-signal transducers and activators of transcription (STAT) signaling pathway. This decreases the production of inflammatory cytokines and may prevent an inflammatory response. In addition, baricitinib may induce apoptosis and reduce proliferation of JAK1/2-expressing tumor cells. JAK kinases are intracellular enzymes involved in cytokine signaling, inflammation, immune function and hematopoiesis; they are also upregulated and/or mutated in various tumor cell types.
An orally available small molecule, irreversible inhibitor of epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Rociletinib binds to and inhibits mutant forms of EGFR, including T790M, thereby leading to cell death of resistant tumor cells. Compared to other EGFR inhibitors, CO-1686 inhibits T790M, a secondary acquired resistance mutation, as well as other mutant EGFRs and may have therapeutic benefits in tumors with T790M-mediated resistance to other EGFR tyrosine kinase inhibitors. This agent shows minimal activity against wild-type EGFR, hence does not cause certain dose-limiting toxicities.
An orally available cyclin-dependent kinase (CDK) inhibitor targets at cyclin D1/CDK4 and cyclin D3/CDK6 cell cycle pathway, with potential antineoplastic activity. Ribociclib specifically inhibits CDK4 and 6, thereby inhibiting retinoblastoma (Rb) protein phosphorylation. Inhibition of Rb phosphorylation prevents CDK-mediated G1-S phase transition, thereby arresting the cell cycle in the G1 phase, suppressing DNA synthesis and inhibiting cancer cell growth. Overexpression of CDK4/6, as seen in certain types of cancer, causes cell cycle deregulation.
A non-nucleoside, polymerase inhibitor of the hepatitis C virus (HCV) nonstructural protein 5B (NS5B), a RNA-dependent RNA polymerase, with potential activity against HCV. Upon administration and after intracellular uptake, beclabuvir allosterically binds to the non-catalytic Thumb 1 site of viral HCV NS5B polymerase and causes a decrease in viral RNA synthesis and replication. The HCV NS5B protein is essential for the replication of the viral HCV RNA genome. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family.
A methylated tryptophan with immune checkpoint inhibitory activity. Indoximod inhibits the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades the essential amino acid tryptophan, and may increase or maintain tryptophan levels important to T cell function. Tryptophan depletion is associated with immunosuppression involving T cell arrest and anergy.
A radiopharmaceutical composed of a mixture of proprietary phospholipid ethers (CLR 1404) that are covalently linked to the cytotoxic radioisotope iodine I 131 (iodine-131), with potential antineoplastic activity. Upon administration of CLR 131, the phospholipid ether (PLE) moiety is selectively taken up by lipid raft microdomains expressed on tumor cells and accumulates in the cytoplasm of tumor cells;. CLR 131 is not taken up by normal, healthy cells. This delivers cytotoxic iodine I 131 directly to and induces cell death in tumor cells. PLEs allows for targeted delivery of the radioisotope.
A selective, orally bioavailable inhibitor of 17beta-hydroxysteroid dehydrogenase type 5 (17bHSD5, aldo-keto reductase 1C3; AKR1C3), with potential antineoplastic activity. Upon administration, ASP9521 selectively binds to and inhibits the activity of 17bHSD5. This prevents the conversion of the adrenal androgens dehydroepiandrosterone and androstenedione into 5-androstenediol and testosterone. By blocking testosterone production, ASP9521 may inhibit the growth of testosterone-dependent cancers such as castration-resistant prostate cancer (CRPC). 17bHSD5, expressed both in normal prostate tissue and in prostate cancer (PC), plays a crucial role in persistent production of androgens despite castration; its expression is associated with increased malignancy of PC.
An orally bioavailable, selective and reversible antagonist of CXC chemokine receptor 2 (CXCR2), with potential anti-inflammatory and antineoplastic activities. Upon administration, CXC chemokine receptor 2 antagonist AZD5069 directly binds to CXCR2 and inhibits its activation. This inhibits CXCR2-mediated signaling and may inhibit tumor cell proliferation in CXCR2-overexpressing tumor cells. In addition, AZD5069 reduces both neutrophil recruitment and migration from the systemic circulation into sites of inflammation, including the lung mucosa; it may also prevent neutrophil migration from the bone marrow. This results in the reduction of inflammation, mucus production, and neutrophil proteinase-mediated tissue destruction in the lung. CXCR2, a G protein-coupled receptor protein also known as IL-8 receptor B (IL-8RB), is upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation and progression; it is known to be elevated in several inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), asthma and fibrotic pulmonary disorders.
A highly selective, potent, and orally bioavailable small molecule inhibitor of the delta isoform of the 110 kDa catalytic subunit of class IA phosphoinositide-3 kinases (PI3K) with potential immunomodulating and antineoplastic activities. PI3K-delta inhibitor AMG 319 prevents the activation of the PI3K signaling pathway through inhibition of the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), thus decreasing proliferation and inducing cell death. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in hematopoietic lineages. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells.
Low ambient oxygen tension associated with ALTITUDE.
Limitations, challenges, and impediments to healthcare practice and patient recovery.
Body mass index 5 percentile to less than 85 percentile
An electrocardiographic finding of pathologic Q waves, which is suggestive of myocardial infarction of one or more regions of the heart, without evidence of current or ongoing acute infarction. No specification is provided for localization. (CDISC)
Diseases of the fourth cranial (trochlear) nerve or its nucleus in the midbrain. The nerve crosses as it exits the midbrain dorsally and may be injured along its course through the intracranial space, cavernous sinus, superior orbital fissure, or orbit. Clinical manifestations include weakness of the superior oblique muscle which causes vertical DIPLOPIA that is maximal when the affected eye is adducted and directed inferiorly. Head tilt may be seen as a compensatory mechanism for diplopia and rotation of the visual axis. Common etiologies include CRANIOCEREBRAL TRAUMA and INFRATENTORIAL NEOPLASMS.
A non-neoplastic proliferation of morphologically bland C-cells with a diffuse growth pattern in the thyroid gland.
Autosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals can have an imbalance of other molecules in the blood as well, including too much phosphate (hyperphosphatemia) or too little magnesium (hypomagnesemia). Some people with autosomal dominant hypocalcemia also have low levels of a hormone called parathyroid hormone (hypoparathyroidism). This hormone is involved in the regulation of calcium levels in the blood. Abnormal levels of calcium and other molecules in the body can lead to a variety of signs and symptoms, although about half of affected individuals have no associated health problems.The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, prickling or tingling sensations (paresthesias), or twitching of the nerves and muscles (neuromuscular irritability) in various parts of the body. More severely affected individuals develop seizures, usually in infancy or childhood. Sometimes, these symptoms occur only during episodes of illness or fever.Some people with autosomal dominant hypocalcemia have high levels of calcium in their urine (hypercalciuria), which can lead to deposits of calcium in the kidneys (nephrocalcinosis) or the formation of kidney stones (nephrolithiasis). These conditions can damage the kidneys and impair their function. Sometimes, abnormal deposits of calcium form in the brain, typically in structures called basal ganglia, which help control movement.A small percentage of severely affected individuals have features of a kidney disorder called Bartter syndrome in addition to hypocalcemia. These features can include a shortage of potassium (hypokalemia) and magnesium and a buildup of the hormone aldosterone (hyperaldosteronism) in the blood. The abnormal balance of molecules can raise the pH of the blood, which is known as metabolic alkalosis. The combination of features of these two conditions is sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V.There are two types of autosomal dominant hypocalcemia distinguished by their genetic cause. The signs and symptoms of the two types are generally the same.
Beta-mannosidosis is an autosomal recessive lysosomal storage disease of glycoprotein catabolism caused by a deficiency of lysosomal beta-mannosidase activity. The most severely affected patients show developmental delay and mental retardation, but there are differing levels of severity and some patients may have comparatively mild disease (Bedilu et al., 2002) The disorder was first described in goats (Jones and Dawson, 1981), who have a more severe neurodegenerative disorder than that seen in humans.
An undifferentiated soft tissue sarcoma characterized by the presence of a malignant spindle cell infiltrate with amphophilic or palely eosinophilic cytoplasm.
A morphologic finding referring to the presence of vacuoles within the cytoplasm of the cells.
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye. [HPO:probinson, PMID:28082927]
An abnormally decreased level of immunoglobulin in blood. [HPO:probinson]
Atrophy of the choroid and retinal layers of the fundus. [HPO:probinson, pmid:20224472]
A disorder characterized by the failure to use developmentally expected speech sounds that are appropriate for the individual's age (i.e., the individual makes errors in sound production or use or omits sounds such as final consonants).
a drug used to relieve nervousness, tension and anxiety
A condition characterized by abnormal proliferation of fibrous tissue in the compartment posterior to the peritoneum, for which no underlying cause has been identified.
A benign, intermediate, or malignant bone tumor characterized by the presence of osteoclast-like giant cells. Clinical presentation includes pain, edema, and decreased range of motion in the affected joint.
An undifferentiated soft tissue sarcoma characterized by the presence of uniform round or ovoid malignant cells with a high nuclear to cytoplasmic ratio.
Multiple endocrine neoplasia caused by mutation of the RET gene. It includes the following neoplastic processes: multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2B, and hereditary thyroid gland medullary carcinoma.
A perfluorocarbon blood substitute in trials for the treatment of severe anemia
A question about whether an individual has or had a lack of energy.
A gonadal or extragonadal malignant neoplasm that arises from germ cells. Representative examples include embryonal carcinoma, yolk sac tumor, and seminoma.
The calcium salt of pentetic acid, a synthetic chelating agent related to the chelating agent ethylenediaminetetraacetic acid (EDTA). Pentetic acid chelates with the metallic radioisotopic moieties of unbound, extracellular radioimmunotherapeutic agents, resulting in higher specific tumor cell binding of radioimmunotherapeutic agents; this results in improved tumor cell radiocytotoxicity and the sparing of normal cells and tissues from the radiocytotoxic effects of these agents.
An uncommon variant of rhabdomyosarcoma with sclerosing morphology. It usually arises from the limbs.
An autosomally dominant inherited form of palmoplantar keratoderma that is characterized by a non-gradient diffuse pattern and often, hyperhidrosis of the palms of the hands and soles of the feet. It does not extend beyond the palms, knucklels pads, nails, and the soles.
An increased concentration of methionine in the blood.
A response indicating that an individual is unable to do something.
Reduced motility through the sphincter of Oddi, resulting in impedance of bile and pancreatic juice flow from the common bile duct into the duodenum. [HPO:probinson]
A benign neoplasm or hamartoma composed of melanocytes.
A replication-defective adenoviral serotype 5 vector encoding a recombinant form of the human cytokine interferon-gamma (IFN-g), with potential antineoplastic and immunoregulatory activities. Upon intratumoral administration, the sustained expression of IFN-g by IFN-g-expressing adenovirus vaccine ASN-002 promotes a T-helper type 1 (Th1) immune response and inhibits the Th2-mediated cytokine production observed in many cutaneous lymphomas. IFN-g also mediates interleukin-12 (IL-12) production by antigen-presenting cells (APCs); activates macrophages, cytotoxic T-cells, and natural killer (NK) cells; upregulates major histocompatibility complex (MHC) molecules; and stimulates antibody-dependent cellular cytotoxicity (ADCC). Altogether, these IFN-g-mediated effects may result in both an inhibition of tumor cell proliferation and tumor cell death. Compared to IFN-g injections, the prolonged local production of IFN-g at the tumor site allows for higher efficacy and a reduction of systemic toxicity.
A formulation of camptothecin, an alkaloid isolated from the Chinese tree Camptotheca acuminata, conjugated with to a hydrophilic, cyclodextrin-based linear polymer with potential antineoplastic activity. Upon intravenous administration, camptothecin is slowly released from the formulation at the tumor site and taken up by tumor cells. During the S phase of the cell cycle, camptothecin selectively stabilizes topoisomerase I-DNA covalent complexes, thereby inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when encountered by the DNA replication machinery. Compared to camptothecin alone, the cyclodextrin-based polymer formulation has a prolonged half life and greatly improves the biodistribution of camptothecin resulting in an accumulation of camptothecin at the tumor site, which enhances tumor exposure while greatly reducing toxic side effects. In addition, cyclodextrin-based polymer-camptothecin may be able to overcome certain kinds of multidrug resistance.
An electrocardiographic finding of supraventricular tachycardia involving the sinus node in which a patient has an atypically high heart rate which cannot be explained by factors such as fever, exercise, hypovolemia, etc.
Infections with bacteria LEPTOSPIRA INTERROGANS.
Sharp pointed superior portion of the ear, with variable overfolding of the helix.
A dysgammaglobulinemia characterized by low or undetectable serum levels of immunoglobulin class A (IgA). It is the most common primary antibody deficiency. It may be inherited or the reversible sequela of infection or certain drugs. It may be caused by decreased or inefficient class-switching from progenitor B cells without any corresponding decreases in the other isotypes. Though affected persons may be asymptomatic, low levels of IgA will reduce the immune system's ability to combat infection where IgA is normally secreted, at mucosal surfaces. Selective IgA deficiency is seen in greater proportion among patients with autoimmune disorders.
Androgenetic alopecia is characterized by a loss of hair from the scalp that follows a defined pattern (Hamilton, 1951). It occurs in women as well as in men. It is caused by a shortening of the anagen (growth) phase and miniaturization of the hair follicle, which results in the formation of progressively thinner, shorter hair (Bergfeld, 1995). In men, the condition is often referred to as male pattern baldness (MPB) and appears to be androgen-dependent (Hamilton, 1942). The condition is hereditary, and follows a pattern that may be consistent with an autosomal dominant trait (Osborn, 1916). Linkage evidence for an autosomal locus on 3q26 (AGA1) has been identified (Hillmer et al., 2008). See 300710 (AGA2) for a discussion of X linkage of androgenetic alopecia. A third locus has been found on chromosome 20p11 (AGA3; 612421).
A sulfonate-based salt form of a trimebutine derivative, an orally available, peripherally-acting opioid agonist and muscarinic antagonist, with potential visceral analgesic activity. Upon oral administration of GIC-1001, this agent may exert its therapeutic effects through the potential mechanisms of action for the trimebutine and sulfonate moieties: The trimebutine moiety can act as a motility enhancer in the gastrointestinal (GI) tract, as an antispasmodic agent to reduce colonic spasms, as an agonist of colonic mu and kappa opioid receptors, which could provide an analgesic effect, and blocks sodium channels and the release of a variety of GI peptides, which modulates the activity of visceral afferents. The sulfonate moiety releases hydrogen sulfide (H2S), which is involved, through an as of yet not fully elucidated mechanism of action, in the modulation of visceral perception and pain, possibly through the activation of ATP-sensitive potassium (KATP) ion channels and mu opioid receptors. Altogether, administration of this agent may both facilitate the insertion of the colonoscope during a colonoscopy and reduce colonic spasms and pain.
A response indicating that something is a little better.
A phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. Copanlisib inhibits the activation of the PI3K signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.
An orally bioavailable small-molecule inhibitor of mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), with potential antineoplastic activity. Cobimetinib specifically binds to and inhibits the catalytic activity of MEK1, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation. Preclinical studies have demonstrated that this agent is effective in inhibiting the growth of tumor cells bearing a B-RAF mutation, which has been found to be associated with many tumor types. A threonine-tyrosine kinase and a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases.
A humanized monoclonal antibody fused to two peptides that bind to angiopoietin 2 (Ang2; ANGPT2), with potential anti-angiogenic and antineoplastic activities. Upon intravenous administration, Ang2-targeting PF-04856884 CovX body specifically binds to Ang2 and prevents the binding of Ang2 to its receptor Tie2 expressed on endothelial cells. This inhibits Tie2-mediated signaling, prevents angiogenesis and inhibits tumor cell proliferation. Ang2, a proangiogenic cytokine and ligand for the Tie2 receptor, plays a key role in the regulation of tumor angiogenesis and tumor cell proliferation; its expression is upregulated by tumor endothelial cells.
A hereditary disorder that leads to a selective defect in renal or intestinal magnesium absorption, resulting in a low serum magnesium concentration.
This syndrome has characteristics of hyperlaxity of the skin involving the entire body. It has been described in six patients. The phenotype is linked to a deficiency in vitamin K-dependent clotting factors and the syndrome has been associated with mutations in the GGCX gene. This gene encodes gamma-glutamyl carboxylase, an enzyme that has already been implicated in congenital vitamin K-dependent clotting factor deficiencies. This syndrome should be distinguished from pseudoxanthoma elasticum and cutis laxa in which the excessive skin folding is limited to specific zones.
Breast carcinoma that does not respond to hormone therapy.
This syndrome describes an explosive-onset, potentially fatal acute epileptic encephalopathy that develops in previously healthy children and adolescents following the onset of a non-specific febrile illness. Usually presents in 3-15 year olds that have previously been healthy and developmentally normal. It always comes after a simple febrile illness. Manifestations include the sudden onset of convulsive and recurrent focal seizures. This is followed by refractory focal epilepsy along with a decline in memory and cognition. Psychiatric disorders and occasionally motor disability can be present in some cases. In serious cases, the disease progression can lead to a vegetative or semi-conscious state or even death. There may be a genetic cause for the disease, as seen in Dravet syndrome, but as yet no causative genes have been identified.
A focal defect in the elastic lamina of the aortic wall that leads to localized medial disruption and potential rupture. []
A type of renal carcinoma affecting mostly young African-Americans. It is located in the medulla of the kidney, and follows an aggressive clinical course. Most reported cases have shown metastatic disease at the time of diagnosis.
Transitory imbalance that may be caused by exercise, tachycardia, or emotion. It is characterized by angina because of the increased oxygen demand.
A rare acquired idiopathic dermal tissue disorder characterised by numerous asymptomatic 2-3 millimetre yellowish, non-follicular papules that tend to converge into cobblestone-like plaques. The plaques are distributed symmetrically over the posterior neck, supraclavicular region, axillae, and sometimes abdomen. Unlike pseudoxanthoma elasticum, these skin lesions show select elimination (absence or marked loss) of elastic fibres in the papillary dermis and there is no systemic involvement.
An eccentric abnormal localized widening (dilatation) of the abdominal aorta that involves only a portion of the circumference of the vessel wall. []
A DNA repair abnormality caused by mutations in one or more genes that are involved in homologous recombination repair. Deficient homologous recombination is associated with numerous neoplastic diseases and developmental disorders related to chromosomal nondisjunction.
A decrease in the number of bone marrow plasma cells to protocol-defined level(s).
Enlargement of the diameter of the ureter, which can be partial or complete.
A benign myoepithelioma characterized by the presence of a minor ductal component.
A finding of diffuse metabolic activity at the primary tumor or nodal sites that is greater than background uptake but less than liver uptake.
A primarily uterine reaction with generally indistinct borders and two recognizable regions. These regions are an antimesometrial region containing closely packed mesenchymal cells and a mesometrial region containing mesometrial cells with long cytoplasmic processes and abundant glycogen. (INHAND)
Gene expression cluster 1 as determined by Recognition of Outliers by Sampling Ends (ROSE) in high-risk B-precursor acute lymphoblastic leukemia.
A decrease in signs of cancer, supported by molecular analysis.
A skin hypersensitivity reaction characterized by raised purpuric lesions, red macules, hemorrhagic blisters and ulcerations.
Familial glucocorticoid deficiency is an autosomal recessive disorder resulting from defects in the action of adrenocorticotropic hormone (ACTH) to stimulate glucocorticoid synthesis in the adrenal. Production of mineralocorticoids by the adrenal is normal. Patients present in early life with low or undetectable cortisol and, because of the failure of the negative feedback loop to the pituitary and hypothalamus, grossly elevated ACTH levels (summary by Clark et al., 2009). Genetic Heterogeneity of Familial Glucocorticoid Deficiency Familial glucocorticoid deficiency-2 (GCCD2; 607398) is caused by mutation in the MRAP gene (609196) on chromosome 21q22. GCCD3 (609197) has been mapped to chromosome 8q11.2-q13.2. GCCD4 with or without mineralocorticoid deficiency (614736) is caused by mutation in the NNT gene (607878) on chromosome 5p12. GCCD5 (617825) is caused by mutation in the TXNRD2 gene (606448) on chromosome 22q11.
The formation of a clot within a stent more than one year after the stent is placed. (Cutlip DE, Windecker S, Mehran R, et al. Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation. 2007;115:2344-2351)
Nephrotic syndrome in which there is relapse occurring two or more times in the first six months, or four or more times in a year.
Segmental scarring of the glomerulus, which may result in isolated proteinuria or nephrotic syndrome, which affects only part of the glomerulus and only some of the glomeruli. Additionally, the Not Otherwise Specified classification excludes FSGS tip, perihilar, collapsing, and cellular variants. (D'Agati VD, et al. ""Pathologic Classification of Focal Segmental Glomerulosclerosis: A Working Proposal."" Am J Kidney Dis 43.2 (2004): 368-82.)
Gene expression cluster 4 as determined by Recognition of Outliers by Sampling Ends (ROSE) in high-risk B-precursor acute lymphoblastic leukemia.
A lung adenocarcinoma characterized by the presence of mildly and moderately differentiated adenocarcinoma cells across the alveolar walls with at least one focus of invasive carcinoma measuring more than 5 mm in greatest dimension.
The formation of a clot within a stent greater than 24 hours but less than thirty days after the stent is placed. (Cutlip DE, Windecker S, Mehran R, et al. Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation. 2007;115:2344-2351)
Familial glucocorticoid deficiency is an autosomal recessive disorder resulting from resistance to the action of adrenocorticotropin (ACTH) on the adrenal cortex, which stimulates glucocorticoid production. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia or overwhelming infection in infancy or childhood (summary by Metherell et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200).
Any structural anomaly of the heart and great vessels.
An electrocardiographic tracing demonstrating atrial fibrillation that is present during the entire recording.
The absence of change or mild changes of metabolic tumor activity in all relevant lesions based on a pre-defined threshold.
The summary or conclusion of the most important radiologic findings.
A rare tumor-like lesion of the hands and feet characterized by the presence of hemorrhagic fibrous tissue, hemosiderin deposition, osteoclast-like giant cells which are irregularly distributed, and reactive bone formation. Pain and swelling are the most frequent symptoms. It may recur following curettage, but is usually cured after a second procedure.
A ureterocele with a small, obstructive orifice.
An electrocardiographic tracing demonstrating three normal QRS complexes followed by a premature ventricular contraction over the course of three or more consecutive cycles; a regularly irregular rhythm of normal to abnormal QRS complexes in a 3-1 ratio.
Chronic tubulointerstitial disease resulting from aristolochic acid.
A ureterocele in which the orifice is distal to the external urinary sphincter.
A decrease in the size and the extent of tissue involvement by cancer, based on physical exam, such as palpation.
Gene expression cluster 5 as determined by Recognition of Outliers by Sampling Ends (ROSE) in high-risk B-precursor acute lymphoblastic leukemia.
The disappearance of all signs of cancer based on physical exam, such as palpation.
An electrocardiographic tracing demonstrating intermittent atrial fibrillation in the presence of sinus rhythm, junctional rhythm, or an atrial paced rhythm.
A decrease in the ability of cells to respond to damaged DNA and to repair the damage. This DNA repair deficiency can be caused by mutations in the genes involved in the DNA damage response and/or DNA repair.
An orally bioavailable 4-thio modified 2-deoxycytidine analog, with potential antineoplastic activity. Upon administration of 4-thio-2-deoxycytidine (TdCyd), this cytidine analog gets incorporated into DNA during replication and inhibits the activity of DNA methyltransferase 1 (DNMT1), which blocks DNA hypermethylation. This results in DNMT1 depletion, hypomethylation of DNA, and the reactivation of tumor suppressor genes that were silenced by hypermethylation; this results in antitumor activity and an inhibition of tumor cell proliferation.
A response indicating that a person finds their extremity to be emotionally acceptable.
An intraosseous benign tumor of notochord origin that arises in the bones of the base of the skull, vertebral bodies, sacrum or coccyx. It contains vacuolated tumor cells without atypia, but lacks myxoid matrix, necrosis, and lobular architecture, which are features that characterize its malignant counterpart, chordoma. Most lesions are incidental findings.
A biochemical reaction that covalently attaches a nitro group to the carbon at position 3 of the side chain benzene ring of L-tyrosine.
A finding of aviremia at a predetermined time point after the end of planned or actual treatment.
The disappearance of cancer in response to treatment, including platelet and white blood cell counts returning to normal levels, a non-palpable spleen, and no immature white blood cells present in the blood unless it is a regenerating marrow following treatment.
A decrease of metabolic tumor activity in all relevant lesions, based on a pre-defined threshold.
An increase of metabolic tumor activity in all relevant lesions, based on pre-defined thresholds, or the development of new lesions.
The disappearance of all signs of cancer, supported by pathological examination.
A finding of metabolic activity at the primary or nodal sites that is greater than liver uptake, but can be attributed to inflammation activity.
A finding of focal metabolic activity at the primary or nodal sites that is greater than liver uptake.
Confirmatory presence of parasitic microorganisms.
A finding of disappearance of metabolic tumor activity in target and non-target lesions, marked by a decrease in tumor standardized uptake value to the level of surrounding normal tissue.
The disappearance of all signs of cancer, supported by molecular analysis.
A finding indicating the involvement of the central nervous system by a malignant neoplasm.
Gene expression cluster 2 as determined by Recognition of Outliers by Sampling Ends (ROSE) in high-risk B-precursor acute lymphoblastic leukemia.
Gene expression cluster 3 as determined by Recognition of Outliers by Sampling Ends (ROSE) in high-risk B-precursor acute lymphoblastic leukemia.
Gene expression cluster 7 as determined by Recognition of Outliers by Sampling Ends (ROSE) in high-risk B-precursor acute lymphoblastic leukemia.
A focal lesion within the uterus consisting of markedly hypertrophied stromal cells with cytoplasmic glycogen and prominent nuclei.
The disappearance of all signs of cancer, including the absence of a detectable disease-related genetic abnormality, as determined by techniques such as karyotyping or FISH, in response to treatment.
A microscopic finding indicating the presence of a cellular infiltrate or isolated cells that have features suspicious for malignancy.
Glomerulonephritis in the context of granulomatosis with polyangiitis in which anti-neutrophil cytoplasm antibody (ANCA) is almost always present.
A gene expression subtype of acute lymphoblastic leukemia characterized by its expression level of the DDIT4L gene.
A finding of aviremia at a specified timepoint, early during the treatment period.
The confirmed disappearance of all signs of cancer, and absence of molecular or cytogenetic marker of disease, in response to treatment with additional biochemical, immunological and histopathological analyses to verify the CR.
A finding of strong focal metabolic activity at the primary or nodal sites that is greater than liver uptake.
A rare, well circumscribed, non-encapsulated tumor that arises in the oral cavity, most often the anterior tongue. It is characterized by the presence of round to spindle cells in a chondromyxoid or hyalinized stroma. Recurrences have been observed in a minority of patients.
Some response with no new symptoms or disease and not meeting partial response.
A traditional Chinese medicine (TCM) containing simo decoction which contains Fructus aurantii, Radix aucklandiae, Semen arecae and Radix linderae, that can potentially be used to improve gastrointestinal (GI) function following surgery. Upon oral intake of simo decoction, this TCM may stimulate mainly muscarinic M3 receptors, but also muscarinic M2 receptors, calcium channels and nicotinic receptors triggering a release of nitric oxide (NO), while inhibiting adrenergic receptors Altogether, this stimulates the contraction of antral circular smooth muscle, thereby abrogating GI hypomotility and enhances the return of GI function after surgery.
The formation of a clot within a stent less than 24 hours after the stent is placed. (Cutlip DE, Windecker S, Mehran R, et al. Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation. 2007;115:2344-2351)
The formation of a clot within a stent greater than thirty days but less than one year after the stent is placed. (Cutlip DE, Windecker S, Mehran R, et al. Clinical End Points in Coronary Stent Trials: A Case for Standardized Definitions. Circulation. 2007;115:2344-2351)
A preparation of autologous transforming growth factor-beta (TGF-beta)-resistant cytotoxic T-lymphocytes (CTL) reactive to human papilloma virus (HPV) types 16 and 18 E6/E7 antigens, with potential antineoplastic activity. Autologous T-lymphocytes from a HPV-positive cancer patient are exposed to and stimulated with dendritic cells (DCs) loaded with the HPV-16/18 proteins E6 and E7. In turn, the HPV-16/18 E6/E7-specific T-lymphocytes are transduced with a retroviral vector expressing a dominant-negative mutant of type II transforming growth factor (TGF)-beta receptor, which blocks signaling mediated by all three TGF-beta isoforms. Following re-administration to patients with HPV-positive tumors, the HPV-16/18 E6/E7-specific TGF-beta-resistant T lymphocytes target HPV16/18 E6/E7-positive cells, which may result in a specific cytotoxic T-lymphocyte (CTL) response, followed by cell lysis and the inhibition of tumor cell proliferation. Tumors expressing TGF-beta inhibit T-lymphocyte activation and expansion.
A recombinant form of the naturally-occurring cytokine interferon-alpha (IFN-a) that has a modified spatial configuration, with immunomodulating, antiviral and antineoplastic activities. Upon administration of recombinant super-compound interferon (rSIFN-co), this agent binds to IFN-specific cell surface receptors, resulting in the transcription and translation of genes whose protein products have antiviral, antiproliferative, anticancer, and immune-modulating effects. The 3-dimensional conformational change improves efficacy and causes less side effects compared to IFN-a.
A cancer vaccine containing pTVG4 plasmid DNA encoding the human androgen receptor (AR) ligand-binding domain (LBD) (pTVG-AR), with potential immunostimulating and antineoplastic activities. Upon intradermal administration of AR LBD-encoding plasmid DNA vaccine MVI-118, the plasmid DNA vaccine expresses AR LBD and may stimulate the host immune system to generate a cytotoxic T-lymphocyte (CTL) response against AR LBD-expressing prostate cancer cells. This reduces proliferation of AR-expressing tumor cells. AR, a tumor-associated antigen (TAA) overexpressed in prostate cancer cells, plays a key role in the development and progression of prostate cancer; its expression is correlated with poor prognosis.
A fusion protein complex composed of heterodimeric IL-15 (hetIL-15), which consists of a synthetic form of the endogenous cytokine interleukin-15 chain (IL-15) complexed to the soluble IL-15 binding protein IL-15 receptor alpha chain (IL-15Ra) (IL15:sIL-15Ra), with potential immunomodulatory, anti-infective and antineoplastic activities. Upon administration, hetIL-15 binds to the IL-2/IL-15 receptor beta-common gamma chain (IL-2Rbeta-gamma) receptor on natural killer (NK) and T-lymphocytes, which activates and increases the levels of NK cells and CD8+ and CD4+ T-cells. The T-cells enhance the secretion of the cytokine interferon-gamma (IFN-g), which further potentiates the immune response against tumor cells. Altogether, this enhances tumor cell killing and decreases tumor cell proliferation. By coupling IL-15 to IL15Ra, this agent has an improved pharmacokinetic profile, shows an increased ability to bind IL-2Rbeta-gamma, and shows increased immunostimulatory activity as compared to IL-15 alone.
A radiotracer consisting of an analogue of the poly(ADP-ribose) polymerase 1 (PARP1) inhibitor rucaparib radiolabeled with the positron emitting isotope fluorine F 18, which can potentially be used for the imaging of PARP1 expression using positron emission tomography (PET). Upon administration, fluorine F 18 fluorthanatrace targets and binds to PARP1. Upon PET, PARP1-expressing tumor cells can be visualized. PARP1, which is overexpressed in many cancer cell types, catalyzes post-translational ADP-ribosylation of nuclear proteins and plays a key role in the repair of DNA strand breaks.
An orally available traditional Chinese medicine (TCM)-based capsule formulation containing Calculus bovis, the dried gallstones of cattle, Moschus, also referred to as deer musk, the resin Olibanum and the resin Myrrha, with potential antineoplastic and chemopreventive activities. Although the exact mechanisms of action through which the active ingredients in the Calculus bovis/Moschus/Olibanum/Myrrha capsule elicit their effects have yet to be fully elucidated, they may, upon intake, exert their antineoplastic activity through modulation of the immune system, inhibition of tumor cell proliferation and induction of apoptosis.
A non-invasive serous neoplasm that arises from the ovary and shows greater cellular proliferation and cytologic atypia as compared to benign ovarian serous tumors, but less as compared to low-grade ovarian serous carcinoma.
A very rare disorder that appears after the first year and a half of life in previously healthy children. It is characterized by rapid-onset weight gain, hypothalamic dysfunction, breathing abnormalities, and autonomic system dysregulation. The hypothalamic dysfunction manifestations include inability to maintain normal water balance, high prolactin levels, low thyroid, low cortisol, and early or late puberty. The breathing abnormalities include sleep apnea and alveolar hypoventilation, requiring ventilation support. The autonomic system dysregulation includes eye abnormalities, intestinal abnormalities, temperature dysregulation, and low heart rhythm. This disorder requires early recognition because it may lead to cardiorespiratory arrest. Up to 40% of the patients develop tumors of neural crest origin.
A very rare benign lesion that arises from the sinonasal tract. It usually affects infants and children. It presents as a polypoid mass and is composed of cartilage, myxoid stroma, and other mesenchymal elements.
A non-invasive neoplasm that arises from the ovary and is composed of gastrointestinal-type, mucin-containing epithelial cells. It shows greater cellular proliferation and cytologic atypia as compared to benign ovarian mucinous tumors.
Human autologous mesenchymal stem cells (MSCs) harvested from the bone marrow of healthy individuals and transduced with a retroviral vector encoding the human cytokine interferon beta (IFNb), with potential immunomodulating and antineoplastic activities. Upon administration of IFNb-secreting MSCs, the cells are attracted and specifically migrate to tumor sites and become part of the tumor microenvironment. Since the MSCs express IFNb, these cells selectively deliver high levels of IFNb to the tumor site. In turn, IFNb binds to IFN-specific cell surface receptors and modulates the transcription and translation of certain genes whose protein products are involved in tumor cell proliferation. This decreases tumor cell growth.
A non-encapsulated, slow-growing, locally aggressive subcutaneous tumor characterized by the presence of adipocytes, hemosiderin-laden spindle cells, hemosiderin-laden macrophages, osteoclast-like giant cells, and scattered chronic inflammatory cells. It usually arises from the dorsum of the foot, ankle, dorsum of the hand, thigh, calf, or cheek. It may recur if it is not completely excised but does not metastasize.
A radioimmunoconjugate consisting of a chimeric monoclonal antibody targeting human cadherin-3 (CDH3) and labeled, via the macrocyclic chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), with the beta-emitting radioisotope yttrium Y 90, with potential antineoplastic activities. Upon administration, the antibody moiety of yttrium Y 90 anti-CDH3 monoclonal antibody FF-21101 binds to CDH3 expressed on tumor cells, thereby specifically delivering cytotoxic beta radiation to CDH3-expressing tumor cells. CDH3, also known as P-cadherin, is a tumor-associated antigen (TAA) and member of the cadherin family; it is overexpressed in a variety of tumors and plays a role in cell adhesion, motility, invasion, and proliferation.
A very rare, nonrhabdoid, intraventricular tumor with relatively favorable prognosis. It is characterized by the presence of neuroepithelial cells forming cribriform patterns, trabeculae, epithelial membrane antigen immunopositivity on epithelial surfaces, and loss of nuclear INI 1 expression.
A rare dermal and subcutaneous lesion that results from the aberrant development of neural crest-derived melanocytes. It affects the head and neck with a predilection for the scalp. It presents as a slowly enlarging multinodular plaque. Morphologically is characterized by the presence of melanocytes and structures with schwannian differentiation in the dermis and subcutaneous tissue.
A metabolite formed during the methylation of 4-hydroxyestrone (4-OHE1) by catechol-O-methyltransferase (COMT) and devoid of any oncogenic or anticarcinogenic activities. The 4-methoxyestrone (4-MeOE1):4-OHE1 ratio can be used to assess methylation efficiency and cancer risk. Lower 4-MeOE1:4-OHE1 ratios suggest inadequate methylation and increased risk of certain cancers.
A metabolite formed during the catabolism of estrone by the liver through the hydroxylation of the carbon at position 16 by cytochrome P450 (CYP) family enzymes, including CYP3A4 and 3A5, with potential carcinogenic activity. With increased estrogenic activity compared to the parent compound, 16alpha-hydroxyestrone (16alpha-OHE1) increases the expression of ER-responsive genes, which leads to increased proliferation of susceptible tumor cells. The ratio between the two estrogen metabolites, 2-hydroxyestrone (2-OHE1), a weak estrogen and metabolite from the 2-hydroxylation pathway, and 16alpha-OHE1, a metabolite from the 16-hydroxylation pathway, may be used to assess the risk of certain cancers; a higher ratio of 2-OHE1:16alpha-OHE1 correlates with decreased cancer risk.
An agonistic monoclonal antibody directed against human death receptor type 5 (DR5), also called tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor 2, with potential pro-apoptotic and antitumor activities. Upon administration, anti-DR5 agonistic antibody DS-8273a mimics the natural receptor ligand TRAIL and binds to DR5. This activates DR5 and leads to the activation of the death receptor signal pathway, which results in the activation of caspase cascades, the induction of tumor cell apoptosis and a reduction in proliferation of DR5-expressing tumor cells. DR5, a member of the TNF receptor superfamily, is expressed on the surfaces of a variety of tumor cells and plays a key role in the induction of tumor cell apoptosis.
An orally bioavailable, small molecule inhibitor of certain class I phosphoinositide 3-kinase (PI3K) isoforms and mammalian target of rapamycin kinase (mTOR) in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR inhibitor LY3023414 inhibits both certain PI3K isoforms and mTOR in an ATP-competitive manner which may inhibit both the PI3K/mTOR signaling pathway in and proliferation of tumor cells overexpressing PI3K and/or mTOR. The PI3K/mTOR pathway is upregulated in a variety of tumor cells and plays a key role in promoting cancer cell proliferation, and survival, motility and resistance to chemotherapy and radiotherapy. mTOR, a serine/threonine kinase downstream of PI3K, may also be activated in a PI3K-independent fashion; therefore, this agent may be more potent than an agent that inhibits either PI3K or mTOR alone. In addition, LY3023414 may inhibit DNA-dependent protein kinase (DNA-PK), thereby inhibiting the ability of tumor cells to repair damaged DNA. DNA-PK is activated upon DNA damage and plays a key role in repairing double-stranded DNA breaks.
An inhibitor of the 19S proteasome-specific deubiquitylating enzymes (DUBs) USP14 and UCHL5, with apoptosis-inducing and antineoplastic activities. Upon administration, VLX1570 specifically binds to both USP14 and UCHL5, thereby blocking their deubiquitylating activity. This blocks the ubiquitin proteasome degradation pathway, prevents the degradation of defective proteins, and leads to an accumulation of poly-ubiquitylated proteins. This induces the unfolded protein response (UPR) and results in both the induction of tumor cell apoptosis and the inhibition of tumor cell growth. USP14 and UCHL5, overexpressed in various tumor cell types, play a key role in the correct folding and deubiquitination of proteins.
An immunotherapeutic combination product composed of LV305, an engineered lentiviral vector that both targets dendritic cells (DCs) and contains nucleic acids encoding the human tumor-associated cancer-testis antigen NY-ESO-1 (CTAG1), and G305, a cancer vaccine comprised of an NY-ESO-1 recombinant protein and glucopyranosyl lipid adjuvant (GLA)-stable emulsion (GLA-SE), with potential synergistic immunostimulatory and antineoplastic activities. Upon intradermal administration of LV305, the DC-targeting lentiviral vector targets and binds to dermal DCs via the DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) receptor. Upon internalization of the vector, the NY-ESO-1 protein is expressed, which stimulates DC maturation, and activates the immune system to mount a cytotoxic T-lymphocyte (CTL) response against NY-ESO-1-expressing cells; this may result in tumor cell lysis. Upon the sequential intramuscular injection of G305, the adjuvant portion of G305 binds to toll-like receptor 4 (TLR-4) expressed on various immune cells, including DCs, monocytes, macrophages and B-cells. The activated DCs present the NY-ESO-1 antigen to CD4-positive Th1 T-lymphocytes. The induction of antigen-specific CD4-positive T-lymphocytes further induces a CTL response against NY-ESO-1-expressing tumor cells. In addition, G305 induces an NY-ESO-1-specific antibody response. NY-ESO-1, expressed in normal testes and on the surfaces of various tumor cells, plays a key role in tumor cell proliferation and survival.
A humanized, immunoglobulin (Ig) G2 monoclonal antibody against the secreted form of human clusterin (sCLU) expressed by tumor cells, with potential antineoplastic and anti-metastatic activities. Upon administration, anti-sCLU monoclonal antibody AB-16B5 specifically binds to tumor-associated sCLU and inhibits its activity. This inhibits both the sCLU-mediated signal transduction pathways and epithelial-to-mesenchymal transition (EMT), which leads to the inhibition of tumor cell migration and invasion. In addition, AB-16B5 enhances chemo-sensitivity. sCLU, a heterodimeric disulfide-linked glycoprotein overexpressed by various types of cancer cells, contributes to proliferation and survival of cancer cells, and stimulates tumor cell EMT.
An agent that inhibits p-cadherin, with potential antineoplastic activity. Upon intravenous infusion, PCA062 binds to and inhibits the activity of p-cadherin. Inhibition of the activity of p-cadherin may inhibit both invasion and proliferation of p-cadherin expressing tumor cells. P-cadherin, a cell-surface protein and member of the cadherin family, is overexpressed in a variety of tumors and plays a role in cell adhesion, motility, invasion, and proliferation.
An engineered toxin body (ETB) composed of the single-chain variable fragment (ScFv) from an antibody targeting CD20 that is linked to a modified form of the ribosome-inactivating alpha subunit of Shiga-like toxin 1 (Shiga-like Toxin-1 A or SLT-1A), with antineoplastic activity. Upon administration, the ScFv moiety of anti-CD20-engineered toxin body MT-3724 targets and binds to the CD20 antigen expressed on tumor cells. Upon internalization, the SLT-1A moiety is released and acts as an N-glycosidase, which binds to and cleaves an adenine nucleobase in the 28S RNA component of the 60S subunit of ribosomes and prevents ribosome activity. This inhibits protein synthesis and eventually leads to apoptosis of CD20-expressing tumor cells. CD20, a B-cell specific transmembrane protein and tumor-associated antigen (TAA), is expressed during most stages of B-cell development and is often overexpressed in B-cell malignancies.
A humanized monoclonal antibody agonist of the cell surface receptor CD40, with potential immunostimulatory and antineoplastic activities. Similar to the endogenous CD40 ligand (CD40L or CD154), CD40 agonistic monoclonal antibody APX005M binds to CD40 on a variety of immune cell types. This triggers the cellular proliferation and activation of antigen-presenting cells (APCs), and activates B-cells, and effector and memory T-cells. This results in an enhanced immune response against tumor cells. APX005M also binds to and activates CD40 present on the surfaces of some solid tumor cells, leading to apoptosis and decreased tumor growth. CD40, a cell surface receptor and member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on various immune cells and certain cancer cells; it mediates both indirect tumor cell killing through the activation of the immune system and direct tumor cell apoptosis.
An anti-CD19/anti-CD3 bispecific, humanized antibody-like protein, with potential immunostimulatory and antineoplastic activities. Anti-CD19/anti-CD3 dual-affinity retargeting (DART) protein JNJ-64052781 possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for CD19, a tumor-associated antigen (TAA) overexpressed on the surface of B-cells. Upon administration, JNJ-64052781 binds to CD3-expressing T-cells and CD19-expressing cancer cells, thereby crosslinking CD19-expressing tumor B-cells and cytotoxic T-lymphocytes (CTLs). This may result in a potent CTL-mediated cell lysis of CD19-expressing B-lymphocytes. CD19, a B-cell specific membrane antigen, is expressed during normal B-cell development and on B-cell malignancies.
A proprietary, hypoxia-activated prodrug with potential antineoplastic activity. Upon administration, the hypoxia-activated prodrug TH-4000 is activated in the hypoxic cells within tumors into an irreversible pan-HER inhibitor via a mechanism of action not yet fully elucidated. As a result, this agent inhibits cellular proliferation and differentiation of tumor cells overexpressing HER kinases, which belong to the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. Healthy, normal tissues may be spared due to the hypoxia-specific activity of this agent, potentially reducing systemic toxicity.
Human peripheral blood T-lymphocytes transduced with a retroviral vector encoding a T-cell receptor (TCR) specific for the cancer-testis antigen NY-ESO-1, with potential antineoplastic activity. Following leukapheresis, isolation of lymphocytes, expansion ex vivo, transduction, and introduction into the patient, the NY-ESO-1-specific TCR gene-transduced T lymphocytes TBI-1301 bind to NY-ESO-1 on tumor cells. This may result in cytotoxic T-lymphocyte (CTL)-mediated elimination of NY-ESO-1-positive cancer cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types.
A recombinant human papillomavirus (HPV), genetically engineered fusion protein vaccine in which the three HPV16 viral proteins L2, E6 and E7 are fused together in a single tandem fusion protein (TA-CIN; HPV16 L2\E6\E7), with potential immunoprotective and antineoplastic properties. Upon administration, HPV16 L2\E6\E7 fusion protein vaccine TA-CIN may stimulate the immune system to generate HPV16 E6\E7-specific CD4+ and CD8+ T-cell responses as well as the induction of L2-specific antibodies. In addition, this vaccine may prevent infection and the development of other HPV16-associated diseases. L2, a minor viral capsid protein, is able to induce a strong antibody response against certain HPV types.
A glyco-engineered monoclonal antibody directed against the receptor tyrosine kinase epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon administration, anti-EGFR monoclonal antibody SYN004 binds to the extracellular domain of EGFR, which prevents ligand binding and the subsequent activation and dimerization of the receptor. This inhibits the activation of EGFR-mediated signaling pathways and inhibits EGFR-dependent tumor cell proliferation. EGFR, a member of the EGFR receptor tyrosine kinase family, may be overexpressed on the cell surfaces of various tumor cell types.
An orally bioavailable small molecule inhibitor of the Wnt signaling pathway, with potential antineoplastic activity. Upon oral administration, Wnt signaling inhibitor SM04755 targets and binds to an as of yet undisclosed target in the Wnt signaling pathway, thereby preventing Wnt-mediated signaling. This may inhibit growth of tumor cells in which the Wnt signaling pathway is overactivated. The Wnt signaling pathway is upregulated in many cancers and plays a key role in tumor cell proliferation.
A proprietary, non-fucosylated monoclonal antibody directed against the cell surface receptor CD40 with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, anti-CD40 monoclonal antibody SEA-CD40 binds to CD40 on a variety of immune cell types, triggering both cellular proliferation and activation of antigen-presenting cells (APCs), which activates B-cells and T-cells, and enhances the immune response against tumor cells. In addition, this agent binds to the CD40 antigen present on the surfaces of tumor cells, which induces antibody-dependent cytotoxicity (ADCC), and eventually inhibits the proliferation of CD40-expressing tumor cells. CD40, a stimulatory receptor and a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on various immune cells, such as macrophages, dendritic cells and various tumor cell types; it plays a key role in the activation of the immune system. The non-fucosylated antibody shows increased efficacy as compared to its fucosylated counterpart.
A chimeric monoclonal antibody directed against human CD20, with potential antineoplastic activity. Anti-CD20 monoclonal antibody SCT400 binds to the B-cell-specific cell surface antigen CD20, which triggers an immune response against CD20-positive B-cells, leading to apoptosis. CD20, a non-glycosylated cell surface phosphoprotein, is exclusively expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell malignancies.
A cancer peptide vaccine containing five human leukocyte antigen (HLA)-A*2402-restricted epitope peptides derived from as of yet not disclosed oncoantigens, with potential immunostimulating and antineoplastic activities. Upon administration of the cancer peptide vaccine S-588410, the peptides may stimulate a cytotoxic T-lymphocyte (CTL) response against cancer cells expressing the antigens. This decreases proliferation of susceptible tumor cells.
A chemical conjugate composed of the dye IR700 linked to cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon injection, the cetuximab moiety targets and binds to EGFR-expressing tumor cells, resulting in the internalization of the conjugate. Upon localized application of near-infrared (NIR) light, the IR700 dye becomes activated, disrupts the cell membrane and selectively kills the EGFR-expressing tumor cells. EGFR, a tyrosine kinase receptor, is overexpressed in a variety of cancers.
A human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1, PCD-1) protein, with potential immune checkpoint inhibitory and antineoplastic activity. Upon administration, anti-PD-1 monoclonal antibody REGN2810 binds to PD-1, inhibits its binding to the PD-1 ligand programmed cell death-1 ligand 1 (PD-L1), and prevents the activation of its downstream signaling pathways. This may restore immune function through the activation of cytotoxic T-cells. PD-1, a transmembrane protein in the immunoglobulin superfamily expressed on activated T-cells, negatively regulates T-cell activation and effector function when activated by its ligand; it plays an important role in tumor evasion from host immunity.
A combination agent composed of the two human monoclonal antibodies VAK694 (VAK296), targeting interleukin-4 (IL-4), and QAX576, targeting IL-13, that can potentially be used to block signaling mediated by IL-4 and IL-13. Upon intravenous administration of the anti-IL-4/IL-13 co,mbination agent QBX258, the two antibodies VAK694 and QAX576 target and block the activity of the two cytokines IL-4 and IL-13, respectively, which prevents IL-4/IL-13-mediated signaling. In patients with breast cancer related lymphedema (BCRL), this agent may prevent lymphedema-associated effects, such as fibrosis, hyperkeratosis, the deposition of fibroadipose tissue, fluid accumulation, limb swelling, reduction of skin elasticity, and pain. By reducing the excess volume, QBX258 may improve lymphatic and arm functions. The development of lymphedema after lymphatic injury is associated with tissue inflammation, the infiltration of CD4-positive cells and their differentiation to the type 2 helper T-cell (Th2) phenotype. Th2 cells produce IL-4 and IL-13 that play a key role in the development of lymphedema-associated symptoms as well as other Th2-mediated diseases.
An orally active inhibitor of the polycomb ring finger oncogene BMI1 (B-cell-specific Moloney murine leukemia virus integration site 1), with potential antineoplastic activity. Upon oral administration, BMI1 inhibitor PTC596 targets BMI1 expressed by both tumor cells and cancer stem cells (CSCs), and induces hyper-phosphorylation of BMI1 leading to its degradation. This inhibits BMI1-mediated signal transduction pathways and results in a reduction of proliferation of BMI1-expressing tumor cells. BMI1, a key protein in the polycomb repressive complex 1 (PRC1), is overexpressed in certain tumor cell types, and plays a key role in CSC survival, proliferation and resistance to chemotherapeutics; its expression is associated with increased tumor aggressiveness and a poor prognosis.
A platinum (Pt)-based agent belonging to the phosphaplatin family comprised of Pt complexed to a pyrophosphate ligand, with potential antineoplastic activity. Although the exact mechanisms through which PT-112 exerts its effect have yet to be fully elucidated, this agent, upon intravenous administration, binds to certain transmembrane proteins and activates several genes involved in tumor suppression and apoptosis. This leads to the activation of various signal transduction pathways, induces S/G2 phase cell cycle, and causes tumor cell apoptosis. In addition, PT-112 may inhibit angiogenesis. Unlike conventional Pt-based chemotherapeutics, PT-112 does not bind to DNA and is able to overcome drug resistance, which occurs with conventional Pt-based chemotherapeutics; it also has a more favorable side effect profile and is more stable in plasma.
An orally bioavailable protein tyrosine kinase inhibitor of mutated forms of the tumor-associated antigen mast/stem cell factor receptor c-Kit (SCFR), with potential antineoplastic activity. Upon oral administration, c-Kit inhibitor PLX9486 binds to and inhibits specific c-Kit mutants. This may result in an inhibition of tumor cell proliferation in cancer cell types that overexpress these c-Kit mutations. c-Kit, a transmembrane protein and receptor tyrosine kinase, is overexpressed in solid tumors and hematological malignancies; it plays a key role in the regulation of cell differentiation and proliferation.
An agonistic antibody that recognizes the co-stimulatory receptor OX40 (CD134;TNFRSF4), with potential immunostimulatory activity. Upon administration, anti-OX40 antibody PF-04518600 selectively binds to and activates OX40; which induces proliferation of memory and effector T-lymphocytes. In the presence of tumor-associated antigens (TAAs), this may promote a T-cell-mediated immune response against TAA-expressing tumor cells. OX40, a cell surface glycoprotein and member of the tumor necrosis factor receptor superfamily (TNFRSF), is expressed on T-lymphocytes and plays an essential role in T-cell activation.
An orally bioavailable adenosine A2A receptor (A2AR) antagonist, with potential antineoplastic activity. Upon administration, A2AR antagonist PBF-509 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This abrogates the adenosine/A2AR-mediated inhibition of T-lymphocytes and activates a T-cell-mediated immune response against tumor cells, thereby reducing proliferation of susceptible tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often produced in excess by cancer cells.
An immunoglobulin (Ig) G1 humanized monoclonal antibody targeting human R-spondin 3 (RSPO3), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the anti-RSPO3 monoclonal antibody OMP-131R10 targets and binds to RSPO3 expressed on tumor cells. This prevents the activation of RSPO3, and inhibits both the binding of RSPO3 to leucine-rich repeat-containing G-coupled receptors (LGRs) and the activation of the RSPO-LGR pathway. This may result in an inhibition of both cancer stem cell (CSC) survival and the proliferation of cancer cells in which this pathway is overactivated. The RSPO-LGR pathway is a CSC pathway activated in a variety of cancer cell types.
An enema containing the osmotic agent polyethylene glycol (PEG) 3350, also called macrogol 3350, with laxative activity. Upon rectal administration of the PEG3350-containing enema NER1008, PEG creates an osmotic gradient, which promotes the retention of water in the bowel. This increases the water content of stool, which results in increased gastrointestinal (GI) motility, decreased stool transit time and evacuation of colonic contents.
A two-component, anti-cancer vaccine containing irradiated tumor cells from a patient, and a capsule implanted with a genetically modified allogeneic cell line that continuously releases granulocyte-macrophage colony stimulating factor (GM-CSF), with potential immune-protective and -boosting activities. Upon subcutaneous injection of MVX-1-loaded macrocapsule/autologous tumor cell vaccine MVX-ONCO-1, the GM-CSF-secreting allogeneic cell capsules and the autologous irradiated cells isolated from the patient's tumor are co-localized in the patient's tissue. This permits the production of GM-CSF and exposes the immune system to the tumor-associated antigens (TAA) expressed by the autologous tumor cells at the injection site. Local expression of GM-CSF recruits and activates antigen-presenting cells (APC), which induces both antibody-dependent cell-mediated cytotoxicity (ADCC) and cytotoxic T-lymphocyte responses at the site of the injection and systemically. This may lead to tumor regression. By using the patient's own irradiated cancer cells as vaccine antigens, the patient's immune system is exposed to the entire repertoire of this individual's TAAs. The encapsulated cell technology (ECT) of GM-CSF-secreting allogeneic cell capsules ensures the continuous release of GM-CSF. GM-CSF, a monomeric glycoprotein that functions as a cytokine, is a strong immune booster and plays an important role in the activation of immune system.
An agonistic humanized monoclonal antibody against the receptor, OX40 (CD134), with potential immunostimulatory and antineoplastic activities. Upon intravenous administration, anti-OX40 monoclonal antibody MOXR0916 selectively binds to and activates OX40, by mimicking the action of endogenous OX40 ligand (OX40L). OX40 activation induces proliferation of effector T-lymphocytes and inhibits the activity of regulatory T-cells. In the presence of tumor-associated antigens (TAAs), this may promote an immune response against the TAA-expressing tumor cells. OX40, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on T-lymphocytes and provides a co-stimulatory signal for the proliferation and survival of activated T-cells.
A formulation containing pegylated liposomal nanoparticles encapsulating a prodrug of the poorly water-soluble, second-generation taxane analog docetaxel, with potential antineoplastic activity. Upon intravenous administration of the liposomal docetaxel prodrug MNK-010, docetaxel is slowly released into the systemic circulation and accumulates at the tumor site due to the unique characteristics of the tumor's vasculature. In turn, docetaxel is taken up by tumor cells, and subsequently binds to and stabilizes the beta-subunit of tubulin, thereby stabilizing microtubules and inhibiting microtubule disassembly. This results in cell cycle arrest and induces cell death. Compared to the administration of docetaxel alone, this formulation is able to increase the delivery of docetaxel into tumors, thereby increasing docetaxel's efficacy while minimizing its toxicity. In addition, this formulation solubilizes docetaxel without the use of toxic solvents, thereby permitting the administration of larger doses of docetaxel while avoiding solvent-associated toxicity.
An antibody directed against the human alpha5beta1 integrin (a5b1) with potential antiangiogenic and antineoplastic activities. Anti-a5b1 antibody MINT1526A selectively binds to a5b1, thereby preventing the binding of integrin ligands. This may result in the inhibition of endothelial cell-cell interactions, endothelial cell-matrix interactions, and integrin-mediated tumor angiogenesis and metastasis in a5b1-expressing tumor cells. a5b1, a cell adhesion and signaling receptor, is often overexpressed on the surface of tumor vessel endothelial cells and plays a crucial role in both endothelial cell adhesion and migration.
A humanized immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-1 monoclonal antibody MEDI0680 binds to and inhibits PD-1 and its downstream signaling pathways. This may restore immune function through the activation of T-cells and cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein in the Ig superfamily expressed on T cells, functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands programmed cell death ligand 1 (PD-L1) or 2 (PD-L2); it plays an important role in tumor evasion from host immunity.
An Fc-optimized humanized immunoglobulin (Ig) G1 monoclonal antibody (MoAb) directed against the inducible T-cell co-stimulator (ICOS, CD278), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-ICOS MoAb MEDI-570 targets and binds to ICOS expressed on tumor infiltrating CD4-positive T-cells. This prevents the interaction between ICOS-positive T-cells and plasmacytoid dendritic cells (pDCs), which express the ICOS ligand (ICOSL). Blocking ICOS activation prevents the pDC-induced proliferation and accumulation of regulatory ICOS-positive T-cells (ICOS+ Tregs) and inhibits interleukin-10 (IL-10) secretion by CD4+ infiltrating T-cells. This may abrogate Treg-mediated immune suppression and may enhance cytotoxic T-lymphocyte (CTL)-mediated immune responses against tumor cells. Fc optimization enhances antibody-dependent cellular cytotoxicity (ADCC). ICOS, a T-cell specific, CD28-superfamily costimulatory molecule and immune checkpoint protein, plays a key role in the proliferation and activation of T-cells. It is normally expressed on both activated CD4+ T-cells, which is a subset of memory T-cells (Tm), and follicular helper T-cells (Tfh). ICOS is highly expressed on Tregs infiltrating various tumors and its expression is associated with a poor prognosis; ICOS-positive Tregs play a key role in immune suppression and tumor immune evasion.
A supplement containing multiple, as of yet undisclosed, carotenoids, with potential chemopreventive activity. Upon oral administration of the multicarotenoid supplement MCS-8, the carotenoids may be able to exert their chemopreventive activity through multiple mechanisms of action.
A preparation of autologous tumor infiltrating lymphocytes (TILs), with potential antineoplastic activity. TILs are isolated from a patient's tumor tissue, cultured in vitro with high-dose interleukin-2 (lL-2), further selected based on antigen specificity and tumor reactivity, and the selected TILs are subsequently expanded. Upon re-introduction of LN-144 into the patient, the TILs re-infiltrate the tumor, specifically recognize the tumor-associated antigens (TAAs), and initiate tumor cell lysis. IL-2 induces the proliferation and expansion of TILs in vitro.
A topical, aqueous gel formulation containing a derivative of ingenol, a selective small-molecule activator of protein kinase C (PKC) that is isolated from the sap of Euphorbia species, with the potential to treat preneoplastic skin lesions. Upon topical application of the ingenol derivative LEO 43204 gel, the agent presumably activates various PKC isoforms, which may induce apoptosis in abnormal cells found in severely sun-damaged skin with multiple actinic keratoses. This may decrease the number of actinic keratoses and prevent the development of skin neoplasms. The PKC family consists of signaling isoenzymes that regulate many cell processes, including proliferation, differentiation, and apoptosis.
A humanized monoclonal antibody directed against the inhibitory receptor lymphocyte activation gene-3 (LAG-3), with potential immunomodulating and antineoplastic activities. Upon administration, the anti-LAG-3 monoclonal antibody LAG525 binds to LAG-3 expressed on tumor-infiltrating lymphocytes (TILs) and blocks its binding with major histocompatibility complex (MHC) class II molecules expressed on tumor cells. This activates antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which leads to a reduction in tumor growth. LAG-3, a member of the immunoglobulin superfamily (IgSF) and expressed on various immune cells, negatively regulates cellular proliferation and activation of T-cells. Its expression on TILs is associated with tumor-mediated immune suppression.
A fully human monoclonal antibody against CD123 (interleukin-3 receptor alpha chain) with potential antineoplastic activity. Anti-CD123 monoclonal antibody KHK2823 binds to and neutralizes CD123, which is upregulated on leukemic stem cells (LSC) found in myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). This agent may inhibit IL-3-dependent signaling and proliferation and may prevent the uncontrolled growth and differentiation of mutated LSC.
An antisense oligonucleotide (ASO) targeting transthyretin (TTR), which has potential use in the treatment of TTR amyloidosis (ATTR). Upon subcutaneous administration, TTR ASO ISIS-TTR Rx targets and binds to messenger RNA (mRNA) for both variant and wild-type forms of TTR inside liver cells, thereby inhibiting translation of both mutant and wild-type TTR. Inhibition of TTR protein synthesis lowers TTR blood levels and decreases the amount of and/or prevents TTR amyloid deposits, which accumulate in and cause damage to various body organs and tissues. ATTR is caused by mutations in the TTR gene, which lead to TTR protein misfolding; misfolded wild-type and mutant forms of TTR protein accumulate in tissues as amyloid deposits in most ATTR patients.
A multi-antigen DNA vaccine consisting of plasmids encoding the hepatitis C virus (HCV) nonstructural proteins 3 (NS3), 4A (NS4A), 4B (NS4B) and 5A (NS5A), with potential immunomodulating and cancer preventive activities. Administered via intramuscular injection followed by electroporation, cells transfected with the HCV DNA vaccine INO-8000 express the encoded HCV proteins, which may elicit a cytotoxic T-lymphocyte (CTL) response against HCV-infected liver cells expressing the NS3, NS4A, NS4B or NS5A proteins. This results in the eradication of HCV-infected cells. HCV, a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family, is associated with the development of hepatocellular carcinoma (HCC).
A plasmid DNA vaccine encoding the tumor-associated antigens (TAAs) prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), with potential immunoactivating and antineoplastic activities. Upon intramuscular delivery and electroporation of the PSA/PSMA DNA plasmid INO-5150, both PSA and PSMA are translated in cells which then activate the immune system. This induces cytotoxic T-lymphocyte (CTL) responses against tumor cells expressing PSA and PSMA. This may result in both immune-mediated tumor cell death and the inhibition of tumor cell proliferation. PSA and PSMA are overexpressed on a variety of cancer cell types. The DNA encoding the TAAs in INO-5150 is based on both human and other primate antigen gene sequences. As the plasmid genes differ from the human gene sequences encoding these antigens, INO-5150 may overcome immune tolerance to human TAAs.
A DNA vaccine consisting of plasmids encoding the E6 and E7 genes of human papilloma virus subtype 6 (HPV-6), with potential immunostimulating and antineoplastic activities. Administered via intramuscular electroporation, HPV-6-targeting immunotherapeutic vaccine INO-3106 expresses the HPV-6 E6 and E7 proteins, which may elicit a cytotoxic T-lymphocyte (CTL) response against tumor cells that are expressing those proteins, resulting in tumor cell lysis. HPV-6 infections are associated with aerodigestive malignancies.
An orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) types 1, 2, and 3 (FGFR1/2/3), with potential antineoplastic activity. FGFR inhibitor INCB054828 binds to and inhibits FGFR1/2/3, which may result in the inhibition of FGFR1/2/3-related signal transduction pathways. This inhibits proliferation in FGFR1/2/3-overexpressing tumor cells. FGFR, a family of receptor tyrosine kinases upregulated in many tumor cell types, plays a key role in cellular proliferation, migration, and survival.
An inhibitor of the Bromodomain and Extra-Terminal (BET) family of bromodomain-containing proteins with potential antineoplastic activity. Upon administration, the BET inhibitor INCB054329 binds to the acetylated lysine recognition motifs on the bromodomain of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth. Characterized by a tandem repeat of bromodomain at the N-terminus, BET proteins, BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during cellular growth.
An inhibitor of the citric acid cycle enzyme isocitrate dehydrogenase [NADP] cytoplasmic (isocitrate dehydrogenase 1; IDH1) with mutations at residue R132 (IDH1(R132)), with potential antineoplastic activity. Upon administration, IDH305 specifically inhibits IDH1(R132) mutant forms in the cytoplasm, which inhibits the formation of the oncometabolite 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH1(R132)-expressing tumor cells. IDH1(R132) mutations are highly expressed in certain malignancies, including gliomas; they initiate and drive cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG.
An orally available, irreversible inhibitor of epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon oral administration, Hemay022 covalently binds to and inhibits the activity of EGFR, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
An orally available inhibitor of members of the Raf family of serine/threonine protein kinases, with potential antineoplastic activity. Upon administration, Raf kinase inhibitor HM95573 binds to and inhibits the B-Raf mutant V600E and C-Raf. This inhibits B-Raf V600E- and C-Raf-mediated signal transduction pathways, thereby inhibiting tumor cell growth of susceptible tumor cells. In addition, HM95573 may also inhibit mutated Ras proteins. Raf protein kinases play a key role in the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival. The Raf mutation B-Raf V600E, where the valine at residue 600 is substituted for glutamic acid, is frequently overexpressed in a variety of human tumors and results in the constitutive activation of the Raf/MEK/ERK signaling pathway.
An immunotherapeutic agent composed of a fusion protein containing the human melanoma-associated antigen MAGE-A3 fused to a lipidated protein D derived from Haemophilus influenzae and combined with the immunoadjuvant AS15, with potential immunostimulating and antineoplastic activities. Upon intramuscular (IM) administration, GSK 2132231A may stimulate a specific cytotoxic T-lymphocyte (CTL) response against MAGE-A3-expressing tumor cells, resulting in tumor cell death. MAGE-A3, a tumor-associated antigen, is upregulated in a variety of cancer cell types. This fusion protein may boost antitumoral immune responses. AS15, a liposomal formulation containing the immunostimulating compounds CpG 7909, 3-O-desacyl-4'-monophosphoryl lipid A (MPL), and QS-21, increases the immune response against MAGE-A3-expressing tumors.
An orally bioavailable, small molecule inhibitor of the delta isoform of phosphoinositide-3 kinase (PI3Kdelta) with potential immunomodulating and antineoplastic activities. Upon oral administration, PI3Kdelta inhibitor GS-9901 selectively binds to the delta isoform of PI3K and inhibits its activity. This inhibits the activation of the PI3Kdelta-mediated signaling pathway and prevents proliferation of PI3Kdelta-overexpressing tumor cells. Unlike other isoforms of PI3K, PI3Kdelta is expressed primarily in certain tumor cell types and plays a key role in tumor cell proliferation, motility and survival. The targeted inhibition of PI3Kdelta is designed to preserve PI3K signaling in normal, non-neoplastic cells and thus reduces toxicity to normal, healthy cells.
An orally bioavailable inhibitor of apoptosis signal-regulating kinase 1 (ASK1), with potential anti-inflammatory, antineoplastic and anti-fibrotic activities. Upon oral administration, ASK1 inhibitor GS-4997 targets and binds to the catalytic kinase domain of ASK1 in an ATP-competitive manner, thereby preventing its phosphorylation and activation. This prevents the phosphorylation of downstream kinases, such as c-Jun N-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (p38 MAPK). By preventing the activation of ASK1-dependent signal transduction pathways, GS-4997 prevents the production of inflammatory cytokines, down-regulates the expression of genes involved in fibrosis, suppresses excessive apoptosis and inhibits cellular proliferation. ASK1, also called mitogen-activated protein kinase kinase kinase 5 (MAP3K5), is activated in response to oxidative and endoplasmic reticulum (ER) stress, calcium influx and infection. It plays a key role in the development of certain cardiovascular and neurodegenerative diseases, diabetes, as well as certain types of cancer.
An orally bioavailable inhibitor of the Bromodomain and Extra-Terminal (BET) family of proteins, with potential antineoplastic activity. Upon administration, the BET inhibitor FT-1101 binds to the acetylated lysine recognition motifs in the bromodomain sites of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to the inhibition of tumor cell growth. BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.
An orally bioavailable inhibitor of inosine 5'- monophosphate dehydrogenase (IMPDH), with potential antineoplastic activity. Upon administration, IMPDH inhibitor FF-10501-01 competitively inhibits the enzyme IMPDH, thereby preventing the conversion of inosine monophosphate to xanthosine monophosphate. This inhibits the synthesis of guanine nucleotides, deprives cancer cells of guanosine triphosphate (GTP), disrupts DNA and RNA synthesis, and decreases tumor cell proliferation. Tumor cells are highly susceptible to IMPDH inhibition because they are rapidly dividing cells that are dependent on rapid DNA synthesis, which requires a high concentration of nucleotides. IMPDH, an enzyme that catalyzes the rate-limiting step in the synthesis of guanosine triphosphate (GTP), is overexpressed in numerous tumor cell types.
A synthetic version of a monoacetyldiacylglyceride naturally occurring in various seed oils, bovine udder and milk fat, antlers of sika deer, with potential antineoplastic activity. Although the exact mechanism of action through which EC-18 exerts its pharmacological effect has yet to be fully identified, upon administration, EC-18 stimulates calcium influx into T-lymphocytes and increases the production of various cytokines, including interleukin (IL) -2, IL-4, IL-12, interferon-gamma (IFN-g), and granulocyte-macrophage colony-stimulating factor (GM-CSF). This stimulates the proliferation of hematopoietic stem cells, bone marrow stromal cells and immune cells, including T- and B-lymphocytes, dendritic cells (DCs) and macrophages. Therefore, EC18 may stimulate the immune system to target cancer cells. In addition, EC-18 enhances the cytolytic activity of natural killer (NK) cells and suppresses the expression of the transmembrane protein tumor cell toll-like receptor 4 (TLR-4) on cancer cells. As activation of TLR-4 enhances immunosuppression and stimulates cancer cell growth, blocking TLR-4 expression suppresses tumor cell proliferation.
A peptide cancer vaccine comprised of peptides derived from the Wilms tumor gene 1 (WT1) protein, with potential immunomodulating and antineoplastic activities. Upon administration, WT1 protein-derived peptide vaccine DSP-7888 may induce a specific cytotoxic T-lymphocyte (CTL) response against WT1-overexpressing tumor cells. In addition, DSP-7888 induces a helper T-lymphocyte-mediated immune response against WT1 expressing tumor cells. WT1 protein, a zinc finger DNA-binding protein and transcription factor, is overexpressed in leukemic cells and in many non-hematological solid tumors.
An antibody directed against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, anti-B7-H3 antibody DS-5573a binds to the cell surface antigen B7-H3, thereby blocking B7-H3-mediated signaling. This abrogates the inhibitory effect on T-cell activation and may activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against B7-H3-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells. It is a negative regulator of the T-cell activation and and its overexpression plays a key role in tumor cell invasion and metastasis.
An orally available third generation thiosemicarbazone and activator of mutant forms of the p53 protein, with potential antineoplastic activity. Upon oral administration, mutant p53 activator COTI-2 targets and binds to the misfolded mutant forms of the p53 protein, which induces a conformational change that normalizes p53 and restores its activity. This induces apoptosis in tumor cells in which the p53 protein is mutated. In addition, COTI-2 inhibits the activation of Akt2 and prevents the activation of the PI3K/AKT/mTOR pathway, thereby inducing apoptosis in cancer cells in which this pathway is overexpressed. p53, a tumor suppressor protein, plays a key role in controlling cellular proliferation and survival. High levels of mutant p53 are seen in many cancers and are associated with uncontrolled cellular growth.
A combination agent composed of two human monoclonal antibodies against the human cytomegalovirus (HCMV), LJP538 and LJP539, with potential immunomodulating activity. Upon administration of CSJ-148, both LJP538 and LJP539 bind to and inhibit the function of viral HCMV glycoproteins that are essential for HCMV infection; LJP538 targets and binds to glycoprotein B (gB) and LJP539 targets and inhibits the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients.
A nanoparticle-based formulation containing the poorly water-soluble, second-generation taxane analog docetaxel, with antineoplastic activity. Upon intravenous administration of the docetaxel-loaded nanopharmaceutical CRLX301, the nanoparticles are able to accumulate at the tumor site due to the unique characteristics of the tumor's vasculature, while avoiding normal, healthy tissue. In turn, CRLX301 is taken up by the tumor cell via macropinocytosis. Subsequently, docetaxel is slowly released into the cytoplasm where it binds to and stabilizes the beta-subunit of tubulin, thereby stabilizing microtubules and inhibiting microtubule disassembly. This prevents mitosis and results in cell death. Compared to the administration of docetaxel alone, this formulation is able to increase docetaxel's efficacy while avoiding systemic exposure, which minimizes its toxicity.
An orally available selective inhibitor of the histone lysine methyltransferase EZH2, with potential antineoplastic activity. Upon oral administration, CPI-1205 selectively inhibits the activity of both wild-type and mutated forms of EZH2. Inhibition of EZH2 specifically prevents the methylation of histone H3 on lysine 27 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased proliferation of EZH2-expressing cancer cells. EZH2, a histone lysine methyltransferase (HMT) class enzyme and the catalytic subunit of the polycomb repressive complex 2 (PRC2), is overexpressed or mutated in a variety of cancer cells and plays a key role in tumor cell proliferation; its expression is correlated with tumor initiation, progression, stem cell self-renewal, migration and angiogenesis.
An orally available inhibitor of the serine/threonine protein kinase family Raf, including A-Raf, B-Raf and C-Raf, with potential antineoplastic activity. Upon administration, pan-RAF kinase inhibitor CCT3833 inhibits Raf-mediated signal transduction pathways, which may inhibit the proliferation of Raf-overexpressing tumor cells. Raf protein kinases play a key role in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival.
A monoclonal antibody targeting the human cell surface antigen CD47, with potential phagocytosis-inducing and antineoplastic activities. Upon administration, anti-CD47 monoclonal antibody CC-90002 selectively binds to CD47 expressed on tumor cells and blocks the interaction of CD47 with signal regulatory protein alpha (SIRPa), a protein expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages. This results in macrophage activation and the specific phagocytosis of tumor cells. In addition, blocking CD47 signaling activates both an anti-tumor T-lymphocyte immune response and T cell-mediated killing of CD47-expressing tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate.
An inhibitor of the Bromodomain (BRD) and Extra-Terminal domain (BET) family of proteins, with potential antineoplastic activity. Upon administration, the BET inhibitor BMS-986158 binds to the acetyl-lysine binding site in the BRD of BET proteins, thereby preventing the interaction between BET proteins and acetylated histones. This disrupts chromatin remodeling and prevents the expression of certain growth-promoting genes, resulting in an inhibition of tumor cell growth. BET proteins (BRD2, BRD3, BRD4 and BRDT) are transcriptional regulators that bind to acetylated lysines on the tails of histones H3 and H4, and regulate chromatin structure and function; they play an important role in the modulation of gene expression during development and cellular growth.
An orally bioavailable inhibitor of raptor-mammalian target of rapamycin (mTOR) complex 1 (mTOR complex 1; mTORC1) and rictor-mTOR complex 2 (mTOR complex 2; mTORC2), with potential antineoplastic activity. Upon oral administration, mTORC1/2 kinase inhibitor BI 860585 binds to the kinase domain of mTOR and inhibits both mTORC1 and mTORC2, in an ATP-competitive manner. This inhibits mTOR-mediated signaling and leads to both an induction of apoptosis and a decrease in the proliferation of mTORC1/2-expressing tumor cells. mTOR is a serine/threonine kinase that is upregulated in certain tumor cell types. It plays an important role in the PI3K/Akt/mTOR signaling pathway, which is often deregulated in cancer cells and promotes cell growth, survival, and resistance to chemotherapy and radiotherapy.
An Fc-engineered, chimeric immunoglobulin (Ig) G1 monoclonal antibody against the tumor-associated antigen (TAA) CD37, with potential antineoplastic activity. Upon administration, the anti-CD37 monoclonal antibody BI 836826 both activates the immune system to induce an antibody-dependent cell-mediated cytotoxicity (ADCC) against CD37-overexpressing tumor cells and induces apoptosis in these tumor cells. BI 836826 is Fc-engineered to improve ADCC activity and enhance affinity for the receptor Fc-gamma-RIIIa, which is expressed on human natural killer (NK) cells. CD37, a member of the tetraspanin superfamily of cell surface antigens, is overexpressed on a variety of cancer cell types and plays a key role in tumor cell proliferation.
An orally available and selective inhibitor of the AXL receptor tyrosine kinase (UFO), with potential antineoplastic activity. Upon administration, BGB324 targets and binds to the intracellular catalytic kinase domain of AXL and prevents its activity. This blocks AXL-mediated signal transduction pathways and inhibits the epithelial-mesenchymal transition (EMT), which, in turn, inhibits tumor cell proliferation and migration. In addition, BGB324 enhances chemo-sensitivity. AXL, a member of the TAM (TYRO3, AXL and MER) family of receptor tyrosine kinases overexpressed by many tumor cell types, plays a key role in tumor cell proliferation, survival, invasion and metastasis; its expression is associated with drug resistance and poor prognosis.
A monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-1 monoclonal antibody BGB-A317 binds to PD-1 and inhibits the binding of PD-1 to the PD-1 ligands programmed cell death-1 ligand 1 (PD-L1), and PD-1 ligand 2 (PD-L2). This prevents the activation of PD-1 and its downstream signaling pathways. This may restore immune function through the activation of both T-cells and T-cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein in the immunoglobulin (Ig) superfamily expressed on activated T-cells, negatively regulates T-cell activation and effector function when activated by its ligands; it plays an important role in tumor evasion from host immunity.
An orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP), with potential antineoplastic activity. PARP inhibitor BGB-290 selectively binds to PARP and prevents PARP-mediated repair of single-strand DNA breaks via the base-excision repair (BER) pathway. This enhances the accumulation of DNA strand breaks, promotes genomic instability, and eventually leads to apoptosis. PARP is activated by single-strand DNA breaks and, subsequently, catalyzes post-translational ADP-ribosylation of nuclear proteins which then transduce signals to recruit other proteins to repair damaged DNA. BGB-290 may both potentiate the cytotoxicity of DNA-damaging agents and reverse tumor cell chemo- and radioresistance.
An inhibitor of the Bromodomain (BRD) and Extra-Terminal domain (BET) family of proteins, with potential antineoplastic activity. Upon administration, the BET inhibitor BAY1238097 binds to the acetylated lysine recognition motifs on the BRD of BET proteins, thereby preventing the interaction between BET proteins and histones. This disrupts chromatin remodeling and prevents the expression of certain growth-promoting genes. This leads to an inhibition of tumor cell growth. BET proteins (BRD2, BRD3, BRD4 and BRDT) are transcriptional regulators that bind to acetylated lysines on the tails of histones H3 and H4, and regulate chromatin structure and function; they play an important role in the modulation of gene expression during development and cellular growth.
An antibody-drug conjugate (ADC) directed against the fibroblast growth factor receptor type 2 (FGFR2) and conjugated to an as of yet unidentified toxin, with potential antineoplastic activity. Upon intravenous administration, the anti-FGFR2 ADC BAY1187982 binds to FGFR2. Upon binding, the toxin selectively induces cell death, through an as of yet undisclosed mechanism of action, in FGFR2-expressing tumor cells. FGFR2, a receptor tyrosine kinase upregulated in many tumor cell types, plays an essential role in tumor cell proliferation, differentiation and survival.
An inhibitor of positive transcription elongation factor b (P-TEFb), which is composed of cyclin-dependent kinase 9 (CDK9) and cyclin-T (CycT), with potential antineoplastic activity. Upon administration, BAY1143572 binds to and inhibits the activity of P-TEFb, thereby preventing the phosphorylation of its downstream target, the carboxyl terminal domain (CTD) of RNA polymerase II (RNA Pol II), and inhibiting the activation of transcriptional elongation by RNA Pol II. This prevents the transcription of tumor promoting genes, induces tumor cell apoptosis, and inhibits tumor cell proliferation. P-TEFb plays an important role in the regulation of gene transcription; over-activation in cancer cells leads to both the transcription of key tumor-promoting genes and cancer cell proliferation.
An orally bioavailable, selective inhibitor of the serine/threonine kinase monopolar spindle 1 (Mps1, TTK), with potential antineoplastic activity. Upon administration, the Mps1 inhibitor BAY 1217389 selectively binds to and inhibits the activity of Mps1. This inactivates the spindle assembly checkpoint (SAC), accelerates mitosis, causes chromosomal misalignment and missegregation, and mitotic checkpoint complex destabilization. This induces cell death in Mps1-overexpressing cancer cells. Mps1, a kinase expressed in proliferating normal tissues and aberrantly overexpressed in a wide range of human tumors, is activated during mitosis and is essential for proper SAC functioning and chromosome alignment.
An orally bioavailable inhibitor of mitogen-activated protein kinase interacting serine/threonine-protein kinase 1 (MKNK1), with potential antineoplastic activity. Upon oral administration, MKNK1 inhibitor BAY 1143269 binds to MKNK1, thereby preventing its activation and the downstream MKNK1-mediated phosphorylation and activation of eukaryotic translation initiation factor 4E (eIF4E). As eIF4E enhances the synthesis of oncogenic proteins, preventing eIF4E activity inhibits the synthesis of tumor angiogenic factors and leads to both the inhibition of cellular proliferation and apoptosis in susceptible tumor cells. eIF4E, overexpressed in a variety of cancer cells, plays a key role in tumor cell proliferation and survival.
A human immunoglobulin G1 (IgG1) monoclonal antibody directed against the fibroblast growth factor receptor type 3 (FGFR3), with potential antineoplastic activity. Upon intravenous administration, the anti-FGFR3 monoclonal antibody B-701 specifically binds to and inhibits both wild-type and mutated forms of FGFR3. This may result in the inhibition of FGFR3 phosphorylation, and thereby preventing its activation and FGFR3-mediated signal transduction pathways. This results in the inhibition of cell proliferation and the induction of cell death in FGFR3-expressing tumor cells. FGFR3, a receptor tyrosine kinase upregulated or mutated in many tumor cell types, plays a key role in tumor cell proliferation.
An orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR), with potential antineoplastic activity. Upon oral administration, FGFR inhibitor ASP5878 binds to and inhibits FGFR, which results in the inhibition of FGFR-mediated signal transduction pathways. This inhibits proliferation in FGFR-overexpressing tumor cells. FGFR, a family of receptor tyrosine kinases upregulated in many tumor cell types, plays a key role in cellular proliferation and survival.
A pegylated derivative of the cyclic tridecapeptide compstatin and inhibitor of complement component C3 (C3) activation, with potential use as a treatment for various diseases in which excessive complement activation plays a key role, including paroxysmal nocturnal hemoglobinuria (PNH) and age-related macular degeneration (AMD). Upon administration, C3-targeted complement inhibitor APL-2 selectively binds to C3 and blocks the cleavage of C3 into C3a and C3b by C3 convertase. This prevents complement pathway activation, and inhibits complement-mediated inflammation and cell lysis. Pegylation increases compstatin's half-life, and increases its efficacy. Excessive complement activation plays a key role in various inflammatory and autoimmune diseases, and leads to tissue destruction. C3 is a crucial and central component of the complement system.
An orally available inhibitor of mutated forms of both isocitrate dehydrogenase type 1 (IDH1, IDH1 [NADP+] soluble) in the cytoplasm and type 2 (IDH2, isocitrate dehydrogenase [NADP+], mitochondrial) in the mitochondria, with potential antineoplastic activity. Upon administration, pan-IDH mutant inhibitor AG-881 specifically inhibits mutant forms of IDH1 and IDH2, thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH mutations. In addition, AG-881 is able to penetrate the blood-brain barrier (BBB). IDH1 and 2, metabolic enzymes that catalyze the conversion of isocitrate into a-KG, play key roles in energy production and are mutated in a variety of cancer cell types. In addition, mutant forms of IDH1 and 2 catalyze the formation of 2HG and drive cancer growth by blocking cellular differentiation and inducing cellular proliferation.
A cancer vaccine containing a live, highly attenuated strain of the Gram-positive bacterium Listeria monocytogenes (LmddA) encoding a fusion protein composed of a chimeric peptide comprised of three highly immunogenic epitopes of the human tumor-associated antigen (TAA) HER2/neu (chHER2) fused to a non-hemolytic fragment of the immunostimulant listeriolysin O (LLO) protein, with potential immunostimulatory and antineoplastic activities. Upon administration of the LmddA-LLO-chHER2 vaccine ADXS31-142, the LmddA is taken up by phagocytic cells; then the listeriolysin portion of the expressed LLO-chHER2 can form pores in the phagolysosomes and the fusion protein can escape into the cytosol. In turn, the LLO-chHER2 is processed and presented to the immune system by major histocompatibility complex (MHC) I on the phagocytic cells. Antigen presentation activates the immune system to exert an immune response involving the recruitment and activation of T-lymphocytes against HER2-expressing tumor cells, and inhibits tumor-infiltrating T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). This eventually results in tumor cell lysis. HER2/neu, a tyrosine kinase receptor belonging to the epidermal growth factor receptor (EGFR) family, is overexpressed in various tumor cell types.
An immunoconjugate consisting of a human immunoglobulin (Ig) G1 monoclonal antibody directed against the alpha subunit of the interleukin-2 receptor (IL-2R alpha or CD25) and conjugated, via a cleavable linker, to a synthetic, cross-linking agent pyrrolobenzodiazepine (PBD) dimer that targets DNA minor grooves, with potential antineoplastic activity. The monoclonal antibody portion of the anti-CD25 antibody-drug conjugate (ADC) ADCT-301 specifically binds to the cell surface antigen CD25. This causes the internalization of ADCT-301 and the subsequent release of the cytotoxic PBD moiety. The imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links in the minor groove of DNA and inhibits DNA replication, which inhibits the proliferation of CD25-overexpressing tumor cells. CD25, a transmembrane receptor and tumor-associated antigen (TAA), is expressed on certain cancer cells.
A human immunoglobulin (Ig) G1 monoclonal antibody directed against the cell surface receptor CD40 with potential immunostimulatory and antineoplastic activities. Upon intratumoral administration, agonistic anti-CD40 monoclonal antibody ADC-1013 binds to CD40 on antigen-presenting dendritic cells, which leads to the activation and proliferation of effector and memory T-cells, and enhances the immune response against tumor cells. In addition, this agent binds to the CD40 antigen present on the surfaces of tumor cells, which induces antibody-dependent cytotoxicity (ADCC). This eventually inhibits the proliferation of CD40-expressing tumor cells. CD40, a stimulatory receptor and a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on various immune cells, such as macrophages, dendritic cells and various tumor cell types; it plays a key role in the activation of the immune system.
An orally available histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity. Upon oral administration, ACY-241 inhibits the activity of HDACs; this results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibit tumor cell division and induce tumor cell apoptosis. HDAC, an enzyme upregulated in many tumor types, deacetylates chromatin histone proteins.
A cell-based cancer vaccine composed of autologous, immature dendritic cells (DCs), with potential immunostimulating and antineoplastic activities. Upon leukapheresis, immature DCs are isolated and re-administered intra-tumorally. The immature DCs internalize and process the tumor-associated antigens (TAAs), migrate to the lymphatic system, and then expose the immune system to the TAAs. This induces a specific cytotoxic T-lymphocyte (CTL) response against the cancer cells leading to tumor cell lysis.
An antibody-drug conjugate (ADC) composed of an as of yet publicly unknown antibody and conjugated to an unknown cytotoxic agent, with potential antineoplastic activity. Upon administration, ADC ABBV-838 binds with its antibody moiety to an as yet not publicly known antigen expressed on tumor cells. Upon binding and internalization, the cytotoxic agent kills the tumor cell.
An inhibitor of one or more as of yet undisclosed bromodomain (BRD)-containing protein(s), with potential antineoplastic activity. Upon administration, the bromodomain inhibitor ABBV-075 binds to the acetyl-lysine binding site in the BRD of certain BRD-containing protein(s), thereby preventing the interaction between those proteins and acetylated histones. This disrupts chromatin remodeling, prevents the expression of certain growth-promoting genes, and leads to an inhibition of cell growth in susceptible tumors.
An orally bioavailable inhibitor of CXC chemokine receptor 4 (CXCR4) with receptor binding and hematopoietic stem cell-mobilization activities. Burixafor binds to the chemokine receptor CXCR4, thereby preventing the binding of stromal derived factor-1 (SDF-1 or CXCL12) to the CXCR4 receptor and subsequent receptor activation; this may induce the mobilization of hematopoietic stem and progenitor cells from the bone marrow into blood. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types; CXCL12/CXCR4 interaction induces retention of hematopoietic cells in the bone marrow.
A human, recombinant monoclonal antibody (MoAb) against macrophage migration inhibitory factor (MIF), with potential immunomodulating, anti-inflammatory and antineoplastic activities. Upon intravenous administration, imalumab binds to MIF, blocking its activity and preventing the MIF-mediated secretion of certain cytokines, including interleukin-1 beta and tumor necrosis factor-alpha. This may lead to an inhibition of cancer cell proliferation in MIF-overexpressing tumor cells. MIF, a pro-inflammatory cytokine overexpressed in some cancers, plays a key role in inflammation, immune responses and cancer cell proliferation.
A Fc-domain optimized IgG monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2) with potential immunomodulating and antineoplastic activities. After binding to HER2 on the tumor cell surface, margetuximab may induce an antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells overexpressing HER2. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. Compared to other anti-HER2 monoclonal antibodies, the Fc domain of MGAH22 is optimized with increased binding to the activating Fcgamma receptor IIIA (CD16A), expressed on cells such as natural killer (NK) cells and macrophages, thereby mediating an enhanced ADCC; the Fc domain also shows decreased binding to the inhibitory Fcgamma receptor IIB (CD32B).
An orally available inhibitor of spleen tyrosine kinase (Syk), with potential antineoplastic activity. Upon oral administration of entospletinib, this agent may inhibit the activity of Syk, which inhibits B-cell receptor (BCR) signaling and leads to an inhibition of tumor cell activation, migration, adhesion and proliferation. Syk, a non-receptor cytoplasmic, BCR-associated tyrosine kinase, is expressed in hematopoietic tissues and is often overexpressed in hematopoeitic malignancies.
An orally available inhibitor of the integral membrane protein gamma-secretase (GS), with potential antineoplastic activity. Upon administration, gamma-secretase inhibitor LY3039478 binds to the GS protease complex, thereby blocking the proteolytic cleavage and release of the Notch intracellular domain (NICD), which would normally follow ligand binding to the extracellular domain of the Notch receptor. This prevents both the subsequent translocation of NICD to the nucleus to form a transcription factor complex and the expression of Notch-regulated genes. This results in the induction of apoptosis and the inhibition of growth in tumor cells that overexpress Notch. Overexpression of the Notch signaling pathway plays an important role in tumor cell proliferation and survival.
An orally bioavailable inhibitor of the proto-oncogene c-Met (also known as hepatocyte growth factor receptor (HGFR)) with potential antineoplastic activity. Capmatinib selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.
An undifferentiated high grade pleomorphic sarcoma that arises from the bone and occurs during childhood.
An undifferentiated high grade pleomorphic sarcoma that arises from the bone and occurs during adulthood.
A humanized monoclonal antibody directed against the Notch-1 receptor with potential antineoplastic activity. Upon administration, brontictuzumab binds to Notch-1 on the cell surface, thereby inhibiting Notch-mediated signaling and tumor cell proliferation. Notch 1, a type 1 transmembrane protein belonging to the Notch family, functions as a receptor for membrane bound ligands and has various roles during development; dysregulated Notch signaling is associated with increased cell growth and chemoresistance in cancers.
A cytogenetic abnormality that refers to the translocation of the short arm (p11) of chromosome 11 and the short arm (p11) of chromosome 16. It results in a FUS-CREB3L1 fusion.
An orally bioavailable inhibitor of the class I phosphatidylinositol 3-kinase (PI3K) alpha isoform (PIK3CA), with potential antineoplastic activity. Taselisib selectively inhibits PIK3CA and its mutant forms in the PI3K/Akt/mTOR pathway, which may result in tumor cell apoptosis and growth inhibition in PIK3CA-expressing tumor cells. By specifically targeting class I PI3K alpha, this agent may be more efficacious and less toxic than pan PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is frequently found in solid tumors and causes increased tumor cell growth, survival, and resistance to both chemotherapy and radiotherapy. PIK3CA, which encodes the p110-alpha catalytic subunit of the class I PI3K, is mutated in a variety of cancer cell types and plays a key role in cancer cell growth and invasion.
The determination of the presence of actual or potential neoplastic tissue which has been left outside the boundary of a resected specimen within the patient.
A humanized, high-chimeric antibody targeting the human cell surface antigen CD47, with potential phagocytosis-inducing and antineoplastic activities. Upon administration, chimeric humanized anti-CD47 antibody selectively binds to CD47 expressed on tumor cells and blocks the interaction of CD47 with signal regulatory protein alpha (SIRPa), a protein expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1), expressed on macrophages. This results in macrophage activation and the specific phagocytosis of tumor cells. In addition, blocking CD47 signaling activates both an anti-tumor T-lymphocyte immune response and T cell-mediated killing of CD47-expressing tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate.
A gluten-free, calorie-rich nutritional supplement containing all essential vitamins, minerals, and trace elements, as well as protein, fat and carbohydrates. The protein contained in this supplement is derived from a variety of sources, including casein, whey, soy and pea; it helps maintain digestive health throughout the gastrointestinal tract and reduces the risk of digestive complications. This supplement contains the essential omega-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexanaeoic acid (DHA). DHA and EPA are incorporated into cell membranes and affect the production of pro-inflammatory mediators, eliciting an anti-inflammatory effect. Medium chain triglycerides (MCT) in this supplement enhance fat absorption. Upon oral intake of this nutritional supplement, the ingredients may prevent both malnutrition and weight loss.
A finding of both karyocytomegaly and multinucleated hepatocytes in the same lesion.
A molecular genetic abnormality indicating the presence of a mutation in exon 14 of the KIT gene located within 4q11-q12.
Peripheral blood lymphocytes (PBLs) transduced with a gene encoding for a thyroglobulin (TG)-specific murine T-cell receptor (mTCR), with potential antineoplastic activity. PBLs are harvested from a thyroid cancer patient, and transfected with a retroviral vector that encodes the mTCR gene specific for the human TG antigen. The transduced PBLs are then expanded in culture. When reintroduced to the patient, these anti-TG mTCR-expressing PBLs target and bind to TG-overexpressing tumor cells, which results in both cytokine secretion and tumor cell lysis. TG is a thyroid-specific protein.
Kidney damage resulting from exposure to calcineurin inhibitors.
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with a mixture of lysates from five allogeneic mesothelioma tumor cell lines, with potential immunostimulatory and antineoplastic activities. Upon leukapheresis, DCs are loaded with allogeneic mesothelioma tumor cell lysates. Upon re-administration of the allogeneic mesothelioma tumor lysate-pulsed autologous DC vaccine, the immune system is exposed to an undefined amount of mesothelioma-associated antigens, which stimulates the induction of a specific cytotoxic T-lymphocyte (CTL) response against mesothelioma tumor cells and leads to tumor cell lysis.
A response that is neither favorable nor unfavorable.
A RNA-lipoplex (RNA-LP)-based cancer vaccine containing four naked ribonucleic acid (RNA)-drug products (DPs) RBL001.1, RBL002.2, RBL003.1, and RBL004.1 encoding melanoma-associated antigens (MAAs) encapsulated in liposomes, with potential antineoplastic activity. Upon intravenous administration of the tetravalent RNA-lipoplex cancer vaccine, the liposomes protect the RNA from degradation in the bloodstream, travel to the spleen and are taken up by antigen-presenting cells (APCs); RNA is translocated to the cytoplasm and translated into the four tumor-associated proteins. The expressed proteins are processed and the human leukocyte antigen (HLA)-peptide complexes are presented to the immune system. This induces antigen-specific CD8+ and CD4+ T-cell responses against the four selected MAAs.
An acute myeloid leukemia associated with inv(3)(q21.3q26.2) resulting in the reposition of a distal GATA2 enhancer to activate MECOM expression. It may present de novo or follow a myelodysplastic syndrome. The clinical course is aggressive.
The underdevelopment of otherwise normal renal parenchyma, characterized by decreased nephron size and possibly a decreased number of nephrons at birth.
Kidney disease associated with Schistosoma infection. Injury to the kidney may be a result of immunologically mediated glomerular or interstitial injury and/or a result of reflux nephropathy.
A form of skeletal dysplasia characterized by shortening of the bones of the proximal segments of the limbs (i.e. the humeri and femora).
Disease progression occurring after a partial response.
The positive pressure that correlates with the maximum dP/dt, the rate of change in pressure over time.
A solution containing the polymer polihexanide, with potential antimicrobial, disinfectant and wound healing activities. Upon application to a wound, polihexanide strongly binds to the wound surface and exerts an antiseptic effect through the binding of the positively charged guanidine groups of polihexanide with the negatively charged phospholipids of the bacterial cell membrane. This compromises the stability of the bacterial cell membrane, which results in the leakage of cytoplasmic components and leads to bacterial cell death. In addition, polihexanide accelerates wound healing by promoting epithelial cell migration and proliferation.
A congenital abnormality of the pituitary that is responsible for pituitary deficiency with usual manifestation of a triad of very thin or interrupted pituitary stalk, an ectopic (or absent) posterior pituitary and hypoplasia or aplasia of the anterior pituitary. In the majority of cases no genetic cause is found, however, the presence of familial forms and the association with microphallus and congenital abnormalities, particularly of the eyes, suggest an antenatal origin.
A group of cell that show altered characteristics in comparison to normal cell types and are confined to a specific area of the sample.
An improvement of neutrophil count as a response to treatment.
Clinical and/or laboratory evidence of reemergence of acute myeloid leukemia less than 12 months from diagnosis.
A molecular genetic abnormality indicating deregulation of the ERG oncogene.
Glomerulonephritis in which anti-neutrophil cytoplasm antibody (ANCA) is almost always present and vasculitis is limited to the kidney.
A pituitary gland microadenoma not associated with a hormonal syndrome.
Kidney damage resulting from exposure to non-steroidal anti-inflammatory drugs (NSAIDs).
The amount of time required to reach a specific tidal volume as measured from the start of exhalation.
A corpus luteum-like structure with a retained oocyte and variably luteinized granulosa cells.
A subjective response indicating that an individual is somewhat satisfied.
A chromosomal translocation involving the ETV6 gene on chromosome 12p13 and HLXB9 gene on chromosome 7q36.
A chromosomal abnormality consisting of the translocation of 5q32 with 17q21.
A cytogenetic abnormality that refers to the translocation involving the genes C11orf95 on chromosome 11 and MKL2 on chromosome 16 resulting in C11orf95-MKL2 fusion.
Kidney damage resulting from exposure to mechanistic target of rapamycin (mTOR) kinase inhibitors.
The average rate of pressure change over time within the left ventricle, which is used as a measurement of left ventricular contractility.
A combination formula consisting of two or more unknown Traditional Chinese Medicine (TCM) ingredients, with potential anti-osteoporotic activity. Upon oral administration, this particular formula of zhongyao fufang may promote increased bone strength and density.
A fusion protein that results from a t(1;3)(p36;q23-25). This fusion protein expression is seen in virtually all cases of epithelioid hemangioendothelioma and is unique to this neoplasm.
An orally bioavailable small molecule targeting the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinases in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. Voxtalisib inhibits both PI3K kinase and mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in susceptible tumor cell populations. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated in a PI3K-independent fashion in response to nutrient and energy deprivation. Accordingly, this agent maybe more potent compared to an agent that inhibits either PI3K kinase or mTOR kinase alone.
A group of conditions comprising dysfunction of the storage and elimination of urine.
A description of the change in viral disease status in response to treatment.
The subject remains viremic during the treatment period and the decrease in viral load from baseline at a specified timepoint is above a predetermined threshold.
The subject remains viremic during the treatment period and the decrease in viral load from baseline at a specified timepoint is below or equal to a predetermined threshold.
The subject remains viremic during the treatment period.
A finding of aviremia at the end of the planned or actual end of treatment period.
A recurrence of the same virus after a finding of aviremia at the end of planned or actual treatment.
The subject becomes viremic during the treatment period after a period of treatment-induced aviremia or has an increase in viral load from nadir above a predetermined threshold during the treatment period.
Birth when a fetus is between 28 weeks and less than 32 weeks gestational age.
Partial response with additional serum and urine M-protein reduction, but not meeting complete response.
Death of a live newborn during the first 24 hours of life
A purified form of the non-ionic polyoxypropylene-based copolymer poloxamer 188 comprised of a hydrophobic core with hydrophilic side chains, with cytoprotective, hemorrheologic, anti-inflammatory, anti-thrombotic and fibrinolytic activities. Although the exact mechanism of action is not fully elucidated, upon intravenous administration, the hydrophobic polyoxypropylene core of vepoloxamer reversibly adheres to hydrophobic sites of damaged cell membranes, thereby fully covering the damaged sites. This prevents the attachment of other hydrophobic molecules, cell leakage of contents, such as ions, and restores the integrity of the damaged cell. Binding of vepoloxamer to damaged cells in the blood vessel walls, prevents cell aggregation and improves blood flow. By occupying damaged sites, this agent also prevents inflammatory processes, inhibits thrombosis, and induces fibrinolysis. As the hydrophobic region of the lipid cell membrane is not exposed in healthy cells, vepoloxamer does not adhere to healthy cells.
An electrocardiographic tracing demonstrating three or more consecutive QRS complexes of ventricular origin, irrespective of rate.
An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the six transmembrane epithelial antigen of the prostate 1 (STEAP1), and conjugated, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration of vandortuzumab vedotin, the monoclonal antibody moiety of vandortuzumab vedotin binds to STEAP1-expressing tumor cells and is internalized, thereby delivering MMAE intracellularly. Proteolytic cleavage releases MMAE, which then binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. STEAP1, a tumor-associated antigen (TAA), is overexpressed in a variety of cancer cell types.
A surgically created external opening into the urinary tract.
The folding of a ureter, which results in the impediment of urine flow.
An increase in tumor size, based on a pre-defined threshold, or the development of new lesion(s), marked central fill-in of a lesion, or new enhancement of a previously homogeneously hypoattenuating nonenhancing mass.
An undifferentiated soft tissue sarcoma which cannot be further characterized.
An undifferentiated soft tissue sarcoma characterized by the presence of a malignant cellular infiltrate with epithelioid morphology.
An electrocardiographic finding of a rhythm that cannot be determined from the EKG, but that clearly does not originate in the ventricles or His Purkinje system. Typically, the QRS complexes are narrow, but aberration or preexcitation may be present.
A disease process that is increasing in scope or severity but the criteria for progressive disease is not met.
An inherited form of tylosis that presents by one year and is characterized by benign palmoplantar keratoderma.
An inherited form of tylosis that presents between 5-14 years of age and is characterized by focal areas of nonepidermolytic palmoplantar keratoderma. Individuals have an increased incidence of esophageal carcinoma.
An evaluation of the change in tumor antigen quantity in response to the therapy.
A targeted prodrug consisting of a recombinant modified form of the Aeromonas protoxin, proaerolysin (PA), bearing a prostate-specific protease cleavage site, with potential antineoplastic activity. When injected directly into the prostate, topsalysin is hydrolyzed to the active toxin aerolysin by the serine protease prostate specific antigen (PSA), a protein overexpressed by prostate cancers and prostate cells in hyperplastic prostatic tissue. Aerolysin molecules then oligomerize to form ring-like heptamers that are incorporated into the lipid bilayers of cell membranes, forming large membrane channels and resulting in the leakage of cellular contents and lysis of PSA-expressing prostate cells.
Segmental glomerulopathy of localized intracapillary foam cells with adjacent, often vacuolated glomerular epithelial cells confluent to the origin of the proximal tubule.
Subnormal production of thyroglobulin, the glycoprotein precursor of thyroid hormones, presumed to result from loss-of-function mutation(s) in the TG gene.
The sensation of constriction or contraction in the throat area.
A finding indicating the involvement of the testis by a malignant neoplasm.
Gross hematuria that occurs at the end of, or immediately after voiding.
A focus of hepatocytes containing well delineated circular clear spaces in the liver, often near mesenteric attachments such as the falciform ligament.
A monoclonal antibody directed against the Notch receptor with potential antineoplastic activity. Tarextumab binds to Notch on the cell surface, thereby inhibiting Notch-mediated signaling and gene transcription, which may impede tumor angiogenesis. Notch receptors are important for cell-cell communication, which involves gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life. Dysregulated Notch signaling is implicated in many diseases including T-ALL (T-cell acute lymphoblastic leukemia), CADASIL (Cerebral Autosomal Dominant Arteriopathy with Sub-cortical Infarcts and Leukoencephalopathy), MS (Multiple Sclerosis), and many other disease states.
Systemic lupus erythematosus nephritis, with global or segmental subepithelial immune deposits or their morphologic sequelae by light microscopy and by immunofluorescence or electron microscopy, with or without mesangial alterations. (Weening, Jan J. et al. (2004). The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. Journal of the American Society of Nephrology 15(2), 241-50.)
Systemic lupus erythematosus nephritis, with 90% or more of glomeruli globally sclerosed without residual activity. (Weening, Jan J. et al. (2004). The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. Journal of the American Society of Nephrology 15(2), 241-50.)
Systemic lupus erythematosus nephritis that appears normal under light microscopy, but with evidence of immune deposits by immunofluorescence. (Weening, Jan J. et al. (2004). The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. Journal of the American Society of Nephrology 15(2), 241-50.)
Systemic lupus erythematosus nephritis, with active or inactive diffuse, segmental or global endo- or extracapillary glomerulonephritis involving greater than or equal to 50% of all glomeruli, typically with diffuse subendothelial immune deposits, with or without mesangial alterations. (Weening, Jan J. et al. (2004). The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. Journal of the American Society of Nephrology 15(2), 241-50.)
Systemic lupus erythematosus nephritis characterized by active or inactive diffuse, segmental endo- or extracapillary glomerulonephritis that involves 50% or more of all glomeruli. (Weening, Jan J. et al. (2004). The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. Journal of the American Society of Nephrology 15(2), 241-50.)
Systemic lupus erythematosus nephritis, characterized by active or inactive diffuse, global endo- or extracapillary glomerulonephritis that involves 50% or more of all glomeruli. (Weening, Jan J. et al. (2004). The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. Journal of the American Society of Nephrology 15(2), 241-50.)
Systemic lupus erythematosus nephritis exhibiting mesangial hypercellularity or mesangial expansion by light microscopy, with mesangial immune deposits. Isolated subepithelial or subendothelial deposits may be visible by immunofluorescence or electron microscopy, but not by light microscopy. (Weening, Jan J. et al. (2004). The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. Journal of the American Society of Nephrology 15(2), 241-50.)
Systemic lupus erythematosus nephritis with active of inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving less than 50% of all glomeruli, typically with focal subendothelial immune deposits with or without mesangial alterations. (Weening, Jan J. et al. (2004). The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited. Journal of the American Society of Nephrology 15(2), 241-50.)
Syringomyelia associated with accumulation of cerebrospinal fluid in the spinal cord.
A topical ointment formulation containing a synthetic form of hypericin, an anthraquinone derivative that is naturally found in the yellow flower of Hypericum perforatum (St. John's wort), with potential antineoplastic and photosensitizing activities. Upon topical administration of the ointment to the tumor site, hypericin becomes activated through the application of visible fluorescent light. During photoactivation, hypericin generates singlet oxygen, which induces DNA damage, necrosis and apoptosis, thereby inhibiting tumor cell growth. The use of visible light for activation avoids the risk of developing secondary malignancies, which are frequently associated with other photodynamic therapies that are dependent on ultraviolet A exposure.
An electrocardiographic tracing demonstrating supraventricular tachycardia of greater than thirty seconds duration. Different thresholds, for rate and/or duration, may apply to different patient populations.
An electrocardiographic tracing demonstrating three or more consecutive QRS complexes of supraventricular origin, irrespective of rate.
The reemergence of a disorder as diagnosed by clinical and/or laboratory evidence following two or more documented periods of remission.
The size and extent of tissue involvement by cancer is neither decreasing nor increasing, based on CT scan and criteria-defined assessments.
An uncommon variant of rhabdomyosarcoma with spindle cell or sclerosing morphology. It affects both children and adults and it is more common in males.
Persistence of mature elongating spermatids in the seminiferous tubules after the normal stage of physiologic release.
Stoppage of flow of sperm due to obstruction.
An electrocardiographic tracing demonstrating the simultaneous occurrence of a slowing sinus rate and AV block.
A humanized monoclonal antibody against lysyl oxidase-like 2 (LOXL2), with potential antineoplastic activity. Anti-LOXL2 monoclonal antibody GS 6624 targets and specifically binds to the scavenger receptor cysteine rich domain 4 (SRCR-4) on LOXL2, thereby preventing the crosslinking of collagen and inhibiting the recruitment and activation of fibroblasts. Inhibiting fibroblast activation and the subsequent production of growth factors and chemokines may lead to an inhibition of tumor cell proliferation. LOXL2, a member of the lysyl oxidase (LO) gene family, is an extracellular, copper-dependent enzyme overexpressed in a variety of tumor cell types, and contributes to tumor cell invasion and metastasis.
Subnormal concentration of the glycoprotein, sex hormone-binding globulin (SHBG), the primary transport protein for androgens and estrogens in serum, resulting in reduced concentrations of total sex steroids, but minimal change in concentrations of free sex steroids.
A monoclonal antibody directed against the human vascular endothelial growth factor (VEGF), with potential antiangiogenic activity. Upon administration, sevacizumab specifically binds to and inhibits VEGF, thereby preventing its binding to VEGF receptors (VEGFRs). This prevents VEGF/VEGFR-mediated signaling and inhibits the proliferation of vascular endothelial cells and tumor cells. VEGF, overexpressed in a variety of cancer cells, is associated with increased invasiveness and decreased survival.
A chondrosarcoma that arises close to the cartilaginous cap of a pre-existing osteochondroma.
Hemophagocytic lymphohistiocytosis due to infections, autoimmune disorders, or underlying malignancies. Signs and symptoms include fever, lymphadenopathy, hepatomegaly, splenomegaly, and pancytopenia.
Collapsing glomerulopathy for which an underlying cause has been identified.
A chondrosarcoma that arises in a pre-existing enchondroma.
A tumor with perivascular epithelioid cell differentiation characterized by the presence of cords of neoplastic cells in a densely collagenous stroma.
An orally bioavailable cyclin dependent kinase (CDK) inhibitor with potential antineoplastic activity. Roniciclib selectively binds to and inhibits the activity of CDK1/Cyclin B, CDK2/Cyclin E, CDK4/Cyclin D1, and CDK9/Cyclin T1, serine/threonine kinases that play key roles in the regulation of the cell cycle progression and cellular proliferation. Inhibition of these kinases leads to cell cycle arrest during the G1/S transition, thereby leading to an induction of apoptosis, and inhibition of tumor cell proliferation. CDKs are often dysregulated in cancerous cells.
A change or slight modification in the epithelial cells along the respiratory tract.
Renal tubular acidosis associated with sensorineural hearing loss, and which is typically associated with recessive mutations.
Tubular dysgenesis resulting from maternal exposure to a class of drugs known as angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB).
A very rare, benign, encapsulated tumor that arises from the kidney. It is characterized by the presence of clear epithelial cells in a prominent smooth muscle stroma.
The return of a disease after a period of complete remission or partial remission.
The return of a disease after a period of complete remission.
A side effect of a drug or other treatment that is serious enough to necessitate a dose modification.
A reluctance to place any body weight on a limb, which is most commonly secondary to pain or discomfort.
Malignant germ cell tumor resistant to treatment.
A malignant germ cell tumor that occurs during childhood and is resistant to treatment.
Acute lymphoblastic leukemia that occurs in childhood and does not respond to treatment.
A megaureter in which there is retrograde flow of urine and a concomitant, episodic obstruction resulting from ureteral folding.
A megaureter that demonstrates retrograde urine flow without ureteral obstruction.
The reemergence of undifferentiated high grade pleomorphic sarcoma of bone in childhood after a period of remission.
The reemergence of lymphomatoid granulomatosis in childhood after a period of remission.
The reemergence of undifferentiated high grade pleomorphic sarcoma of bone in adulthood after a period of remission.
A tumor of the rat that arises from nerve tissue outside of the central nervous system.
An insulin-producing neuroendocrine tumor arising from beta cells of the rat pancreas.
A benign or malignant neuroendocrine neoplasm of the rat sympathetic nervous system that secretes catecholamines. It arises from the chromaffin cells of the rat adrenal medulla.
A broad classification for uncommon disorders in which the development of neoplasms occur in association with a characteristic set of signs or symptoms. These disorders commonly have a genetic basis. The types of neoplasms themselves are not necessarily uncommon.
An evaluation of the radiologic response of the disease to the therapy.
Tissue damage to the glomerulus and renal tubules resulting from irradiation, which is characterized by vascular endothelial damage, mesangial damage, platelet aggregation in the capillary loops, thickening of the glomerular arteriolar intimal layer, and atrophic tubules.
Gene expression cluster 8 as determined by Recognition of Outliers by Sampling Ends (ROSE) in high-risk B-precursor acute lymphoblastic leukemia.
Gene expression cluster 6 as determined by Recognition of Outliers by Sampling Ends (ROSE) in high-risk B-precursor acute lymphoblastic leukemia.
The measurement of the ability of the lung to store energy, which is required for passive expiration. Reactance consists of two components: the negative component reflects capacitive behavior (C) and corresponds to both the thoraco-pulmonary elasticity and to changes in the available lung volumes in the distal compartments of the lung; the positive component of reactance has inertial characteristics (I) describing the moving air column in the bronchial tree.
A measure of the lung's ability to stretch and expand, either statically, the change in volume for a given applied pressure, or dynamically, the elasticity of the lung at any given time during the actual movement of air.
A parenchymal lesion, which may appear neoplastic in origin, that results from abnormal architecture of the renal calyx.
Deficiency or dysfunction of the enzyme prohormone convertase 1 associated with loss-of-function mutation(s) in the PCSK1 gene.
There is an increase in the size and extent of tissue involvement by cancer, based on CT scan and criteria-defined assessments.
Disease progression or the return of a disease after a period of remission, occurring after a hematologic improvement.
Deficiency of the hormone precursor, pro-opiomelanocortin, associated with loss-of-function mutation(s) in the POMC gene.
A non-Hodgkin lymphoma that arises from the bone, without lymph node or other extranodal involvement. The femur, spine, and pelvic bones are the most frequently affected areas. The majority of cases are diffuse large B-cell lymphomas. Most patients present with pain in the affected area. Systemic symptoms are rare.
Collapsing glomerulopathy for which no underlying cause has been identified.
The positive pressure that correlates with the minimum dP/dt, the rate of change in pressure over time.
A posterior urethral valve, presumed to result from incomplete canalization of the urethra, that is located immediately distal to the vera montanum.
A posterior urethral valve extending from the vera montanum towards the distal meatus.
Death between 28 days and 1 year of life.
An infection at an anatomic location used for vascular access.
Obesity associated with variations in multiple genes.
An anomaly in the pituitary stalk that can be developmental, inflammatory, infiltrative, iatrogenic or traumatic.
An orally bioavailable inhibitor of the receptor tyrosine kinase (RTK) epidermal growth factor receptor (ErbB; EGFR) family, with potential antineoplastic activity. Upon administration, pirotinib selectively and irreversibly binds to and inhibits the epidermal growth factor receptors 1 (ErbB1; EGFR), 2 (ErbB2; HER2), and 4 (ErbB4; HER4). This may result in the inhibition of cell growth and angiogenesis in tumors overexpressing these RTKs. EGFRs play major roles in both tumor cell proliferation and tumor vascularization, and are overexpressed in many cancer cell types.
A leukemia subtype characterized by a gene-expression profile similar to that of BCR-ABL1-positive acute lymphoblastic leukemia, alterations of lymphoid transcription factor genes, and a poor outcome.
A cancer vaccine consisting of one or more long, synthetic peptides derived from patient-specific breast cancer tumor-associated antigens (TAAs), with potential immunomodulating and antineoplastic activities. Upon intramuscular administration of the personalized synthetic long peptide breast cancer vaccine, the peptides stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the TAAs, which results in tumor cell lysis.
An intracranial edema that develops around a tumor in the meninges or brain.
A relative measurement (percentage) of in situ component present in a carcinoma compared to the entire malignant cellular proliferation.
The diffusion capacity of the lungs for carbon monoxide adjusted for hemoglobin concentration, expressed as a proportion of the predicted normal value.
The diffusion capacity of the lungs for carbon monoxide adjusted for the ratio of hemoglobin concentration to alveolar volume, and expressed as a proportion of the predicted normal value.
The degree to which inhaled carbon monoxide diffuses from the alveoli into the blood, expressed as a proportion of the predicted normal value.
The calculated ratio of the lung's alveolar volume with respect to its diffusion capacity for carbon monoxide, expressed as a proportion of the predicted normal value.
Glomerulonephritis in the context of systemic, small vessel vasculitis in which anti neutrophil cytoplasm antibody (ANCA) is almost always present.
Glomerulonephritis in the context of eosinophilic-rich granulomatosis with polyangiitis, eosinophilia, asthma and commonly anti-neutrophil cytoplasmic antibody.
Glomerulonephritis with paucity of glomerular staining for immunoglobulins that may be accompanied by systemic, small vessel vasculitis containing no anti neutrophil cytoplasm antibody (ANCA).
An evaluation of the pathologic response of the disease to the therapy.
A decrease in the size and extent of tissue involvement by cancer, based on CT scan and criteria-defined assessments.
Mixed attenuation and some homogeneity of the metastases with a partially resolved peripheral rim.
A humanized IgG1 monoclonal antibody directed against the epidermal growth factor-like domain multiple 7 (EGFL7) with potential antineoplastic activity. Parsatuzumab binds to EGFL7, thereby preventing the activities of EGFL7 on endothelial cells and inhibiting the survival and migration of endothelial cells during angiogenesis. EGFL7, a vascular-restricted extracellular matrix protein which is upregulated during angiogenesis and which regulates vascular development, may be overexpressed on the cell surfaces of various solid tumor cell types.
An abnormality of the pancreatic and biliary ducts in which their junction occurs above the duodenal wall.
An immunohistochemical test result that indicates overexpression of PD-L1 in a tissue sample of a primary or metastatic malignant neoplasm.
Postnatal Hydronephrosis with the following clinical findings: 1) calyceal dilation and the ureter are the same as those in UTD P2, 2) the renal parenchymal is thinned, has increased echogenicity and/or has decreased corticomedullary differentiation, or 3) the bladder is abnormal (wall thickening, ureterocele, posterior urethral dilation). Cases in which there are parenchymal abnormalities but the APRPD is less than 15 mm, are classified as UTD P3. (Adapted from: Hiep T. Nguyen, Carol B. Benson, Bryann Bromley, Jeffrey B. Campbell, Jeanne Chow, Beverly Coleman, Christopher Cooper, Jude Crino, Kassa Darge, C.D. Anthony Herndon, Anthony O. Odibo, Michael J.G. Somers, Deborah R. Stein; Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system); Pediatric Urology; December 2014 Volume 10, Issue 6, Pages 982-998)
Postnatal Hydronephrosis with the following clinical findings: 1) APRPD is greater than or equal to 15 mm, 2) the calyces may be dilated centrally and peripherally, 3) or a dilated ureter is visible, 4) the parenchymal thickness and appearance is normal, and 5) the bladder is normal. Cases in which there is peripheral calyceal dilation but the APRPD is less than 15 mm are classified as UTD P2. (Adapted from: Hiep T. Nguyen, Carol B. Benson, Bryann Bromley, Jeffrey B. Campbell, Jeanne Chow, Beverly Coleman, Christopher Cooper, Jude Crino, Kassa Darge, C.D. Anthony Herndon, Anthony O. Odibo, Michael J.G. Somers, Deborah R. Stein; Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system); Pediatric Urology; December 2014 Volume 10, Issue 6, Pages 982-998)
Postnatal Hydronephrosis with the following clinical findings: 1) APRPD is 10 to less than 15 mm, 2) central calyceal dilation may be present, but peripheral calyceal dilation is considered to increase risk, 3) renal parenchyma should have normal thickness and appearance, 4) the ureter is not seen, and 5) the bladder is normal. If there is central calyceal dilation but the APRPD is less than 10 mm, it is still considered UTD P1. (Adapted from: Hiep T. Nguyen, Carol B. Benson, Bryann Bromley, Jeffrey B. Campbell, Jeanne Chow, Beverly Coleman, Christopher Cooper, Jude Crino, Kassa Darge, C.D. Anthony Herndon, Anthony O. Odibo, Michael J.G. Somers, Deborah R. Stein; Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system); Pediatric Urology; December 2014 Volume 10, Issue 6, Pages 982-998)
The volume of oxygen consumed by the body per heartbeat while at rest.
A benign, unilateral tumor that arises from the ovary and is characterized by the presence of conspicuous microcystic changes, cellular areas, and a fibrous stroma.
The anatomic location of a surgically created ostomy.
An abnormal enlargement of an organ, particularly an organ of the abdominal cavity.
Hypo-attenuation of the metastases which may appear pseudocystic, perfectly homogeneous, and devoid of a recognizable peripheral rim.
A megaureter in which there is obstruction to the flow of urine at the ureterovesical junction.
Diffuse glomerular (greater than 50% of glomeruli) hypertrophy (greater than 250 micron diameter) that occurs in the context of obesity.
A measurement of the total number of birth events at which the gestational age of the neonate is less than 37 weeks and 0 days.
A measurement of the total number of birth events at which the gestational age of the neonate is 39 weeks and 0 days through 40 weeks and 6 days.
A measurement of the total number of birth events at which the gestational age of the neonate is 37 weeks and 0 days through 38 weeks and 6 days.
A value that specifies the relationship of a value to a normal range or reference range of values.
An electrocardiographic tracing demonstrating supraventricular tachycardia of less than thirty seconds duration. Different thresholds, for rate and/or duration, may apply to different patient populations.
A megaureter in which there is no obstruction at the ureterovesical junction and no vesicoureteral reflux.
A megaureter in which there is no obstruction at the ureterovesical junction.
The deviation of the existing water-tissue diffusion pattern from that of a perfect Gaussian curve, which is usually demonstrated via an image finding derived from a form of magnetic resonance imaging, known as diffusional kurtosis imaging.
A pituitary gland macroadenoma not associated with a hormonal syndrome.
A leiomyosarcoma arising from an anatomic site other than skin.
A drug used to alter the progression of autoimmune disease that is not a biologic.
Following a previous assessment of progressive disease unconfirmed (PDu) of non-target lesion(s), the subsequent required assessment does not confirm progressive disease.
A response indicating that an individual has or had no shortness of breath.
Deficiency or dysfunction of the type 2 receptor for neurotropic tyrosine kinase associated with loss-of-function mutation(s) in the NTKR2 gene.
Nephrotic syndrome in which proteinuria has decreased by at least 50% and below the nephrotic range cutoff from disease onset, but does not normalize following a defined course of treatment.
Nephrotic syndrome attributed to mutation(s) in the WT1 gene.
Nephrotic syndrome associated with a toxoplasmosis infection.
Nephrotic syndrome attributed to mutation(s) in the TRPC6 gene.
Nephrotic syndrome associated with a syphilis infection.
Nephrotic syndrome associated with a simian virus 40 infection.
Nephrotic syndrome attributed to mutation(s) in the SMARCAL1 gene.
Nephrotic syndrome attributed to mutation(s) in the SCARB2 gene.
Nephrotic syndrome characterized by recurrent proteinuria by dipstick of first morning urine: 2+ or greater for three days or longer, or the presence of edema with proteinuria of any duration following a remission.
Nephrotic syndrome associated with a parvovirus B19 infection.
Nephrotic syndrome attributed to mutation(s) in the PTPRO gene.
Nephrotic syndrome attributed to mutation(s) in the PLCE1 gene.
Nephrotic syndrome attributed to mutation(s) in the PDSS2 gene.
Nephrotic syndrome attributed to mutation(s) in the NPHS2 gene.
Nephrotic syndrome attributed to mutation(s) in the NEIL1 gene.
Nephrotic syndrome associated with malaria.
Nephrotic syndrome attributed to mutation(s) in the MYO1E gene.
Nephrotic syndrome attributed to mutation(s) in the MEFV gene.
Nephrotic syndrome attributed to mutation(s) in the LMX1B gene.
Nephrotic syndrome attributed to mutation(s) in the LAMB2 gene.
Nephrotic syndrome associated with an infectious process.
Nephrotic syndrome attributed to mutation(s) in the ITGB4 gene.
Nephrotic syndrome attributed to mutation(s) in the ITGA3 gene.
Nephrotic syndrome attributed to mutation(s) in the INF2 gene.
Nephrotic syndrome associated with human immunodeficiency virus infection.
Nephrotic syndrome associated with a hepatitis C infection.
Nephrotic syndrome associated with hepatitis B.
Nephrotic syndrome associated with Epstein-Barr infection.
Nephrotic syndrome attributed to mutation(s) in the EMP2 gene.
Nephrotic syndrome attributed to mutation(s) in the DGKE gene.
Nephrotic syndrome associated with a cytomegalovirus infection.
Nephrotic syndrome attributed to mutation(s) in the CUBN gene.
Nephrotic syndrome attributed to mutation(s) in the CRB2 gene.
Nephrotic syndrome attributed to mutation(s) in the COQ6 gene.
Nephrotic syndrome attributed to mutation(s) in the COQ2 gene.
Nephrotic syndrome attributed to mutation(s) in the CFH gene.
Nephrotic syndrome attributed to mutation(s) in the CD2AP gene.
Nephrotic syndrome attributed to mutation(s) in the ARHGDIA gene.
Nephrotic syndrome attributed to mutation(s) in the ARHGAP24 gene.
Nephrotic syndrome attributed to mutation(s) in the ANLN gene.
Nephrotic syndrome attributed to mutation(s) in the ADCK4 gene.
Nephrotic syndrome attributed to mutation(s) in the ACTN4 gene.
Kidney damage resulting from tacrolimus.
Kidney damage resulting from ciclosporin.
Kidney damage resulting from analgesic drugs.
Kidney damage resulting from amphotericin.
Kidney damage resulting from aminoglycosides.
Nephropathy associated with rhabdomyolysis.
A benign or malignant lesion that occurs in the neonatal period.
A combination preparation containing the aminoglycoside antibiotic neomycin sulfate, the polypeptide antibiotic polymyxin B sulfate and bacitracin zinc, with topical antibacterial activity. Polymyxin B sulfate, a polypeptide produced by Bacillus polymyxa, binds to negatively charged phospholipids in the cell membrane, thereby altering the permeability of the bacterial cytoplasmic membrane. Neomycin sulfate, an aminoglycoside antibiotic, irreversibly binds to the bacterial 30S ribosomal subunit, thereby preventing mRNA from binding to the 30S subunit, causes misreading and inhibits protein synthesis.
An immunogenic peptide sequence that is specifically expressed by a tumor and is not found in normal tissues. One or more of these tumor-associated antigens (TAAs) can be used to develop patient-specific tumor vaccines.
A humanized, agonistic monoclonal antibody against P selectin glycoprotein ligand-1 (PSGL-1; SELPLG; CD162), with potential immunosuppressive activity. Upon administration, neihulizumab specifically targets and binds to CD162 expressed on activated T-lymphocytes. This induces apoptosis of activated T-cells and reduces T-cell-mediated immune responses. This may halt disease progression of T-cell-mediated autoimmune diseases and acute graft-versus-host disease (GvHD).
A subgroup of complete response of multiple myeloma or plasma cell leukemia. It is characterized by less than 5% plasma cells in the bone marrow, unmeasurable serum and urine monoclonal proteins by electrophoresis, and positive serum and/or urine immunofixation.
A nanoparticle-based formulation containing the poorly water-soluble, second-generation taxane analog docetaxel covalently conjugated to proprietary and as of yet undisclosed degradable linkers and encapsulated in polymers, with antineoplastic activity. Upon intravenous administration of nanoparticle-encapsulated docetaxel, the nanoparticles are able to accumulate at the tumor site due to the unique characteristics of the tumor's vasculature, while avoiding normal, healthy tissue. Docetaxel is released and becomes active upon cleavage from various linkers at a predetermined and controlled rate which is dependent on the properties of the proprietary linkers. In turn, active, unconjugated docetaxel binds to the beta-subunit of tubulin, stabilizes microtubules and inhibits microtubule disassembly. This prevents mitosis and results in tumor cell death. Compared to the administration of docetaxel alone, this formulation is able to increase docetaxel's efficacy while avoiding systemic exposure, which minimizes its toxicity. By using different linkers, docetaxel can be released at various rates.
A nanoparticle-based formulation composed of a microRNA 16 (miR-16) mimic, a double-stranded, 23 base pair, synthetic RNA molecule, encapsulated in nonliving bacterial minicells and coated with anti-epidermal growth factor receptor (EGFR) antibodies, with potential antineoplastic activity. Upon intravenous administration and subsequent transfection, nanocell-encapsulated miR-16-based microRNA mimic targets EGFR-expressing tumor cells and facilitates the restoration of expression of the miR-16 family. This leads to the downregulation of the expression of tumor promoting genes and the inhibition of tumor cell growth. In addition, restoration of miR-16 expression sensitizes the tumor cell to certain chemotherapeutic agents. miR-16, a family of microRNAs, is critical to the regulation of gene expression and appears to have a tumor suppressor function; its expression is downregulated in various cancer cell types.
A molecular abnormality indicating rearrangement of the NUP98 gene.
An evaluation of the morphologic response of the disease to the therapy.
The disappearance of all cells with morphologic characteristics of leukemia, accompanied by bone marrow recovery, in response to treatment. Hematologic recovery is not required. Leukemia free state can be a hypocellular marrow.
The disappearance of all signs of cancer, supported by morphological analysis.
The disappearance of all cells with morphologic characteristics of cancer, accompanied by incomplete bone marrow recovery, as evidenced by persistent anemia, thrombocytopenia or neutropenia.
Obesity associated with an identifiable mutation in a single gene.
An evaluation of the molecular response of the disease to the therapy.
A response indicating that an individual has or had moderate shortness of breath.
Birth when a fetus is between 32 weeks and less than 37 weeks gestational age.
A morphologic finding indicating the presence of a mixture of embryonal and alveolar components in a rhabdomyosarcoma.
A minor decrease in signs of cancer, supported by pathological examination and based on pre-defined thresholds.
A peptide-based vaccine containing a carbohydrate mimetic peptide (CMP) P10s fused to the pan HLA DR-binding epitope (PADRE) peptide, with immunomoadjuvant activity and potential antineoplastic activity. Upon injection of the mimotope-P10s-PADRE peptide vaccine, the P10s peptide, which mimics gangliosides and other tumor-associated carbohydrate antigens (TACA), both stimulates a cytotoxic T-lymphocyte (CTL) response towards cells expressing TACAs and induces the production of antibodies that are reactive with a broad set of TACAs. Additionally, the anti-TACA antibodies may interfere with cellular pathways involved in tumor cell survival and may induce antibody-dependent cellular cytotoxicity (ADCC) toward cells expressing TACAs. PADRE is a helper T-cell epitope that is able to increase the magnitude and duration of the CTL response.
A response indicating that an individual has or had mild shortness of breath.
The rarest histopathologic subtype of Schwannoma. The reported cases have been located in the gastrointestinal submucosa or subcutaneous tissue. Morphologically it is characterized by the presence of a microcyst-rich network of spindle cells with minimal amount of cytoplasm and Antoni A tissue.
A rare chondroblastoma that has metastasized to another anatomic site.
An evaluation of the metabolic response of the disease to the therapy.
A process characterized by the degeneration of mesangial cells and the dissolution of the mesangial matrix in the glomerulus of the kidney, in response to injury or disease.
A hamartoma characterized by the presence of collections of non-neoplastic arachnoidal cells.
A rare vascular malformation in the cerebral cortex and overlying leptomeninges. It can occur sporadically or in association with neurofibromatosis type 2.
Membranous nephropathy due to thrombospondin type-1 domain-containing protein 7A (THSD7A) antibodies.
Membranous nephropathy due to phospholipase 2 receptor (PLA2R) antibodies.
Membranous nephropathy due to neural endopeptidase (NEP) antibodies.
Membranous nephropathy in the context of malignancy.
Glomerulonephritis with electron dense deposits in the glomerular baseement membrane, associated with an infection known to cause membranous nephropath and after exclusion of alternative causes.
Membranous nephropathy associated with exposure to a drug.
Membranous nephropathy associated with an autoimmune disorder.
Membranous nephritis associated with systemic lupus erythematosus.
Glomerulonephritis similar in appearance under light microscopy to membranoproliferative glomerulonephritis (MPGN) I, but with subepithelial or transmembranous and subendothelial deposits on electron microscopy.
An abnormality in the biochemical pathway involving the melanocortins, a group of peptide hormones associated with anorexogenic signaling in the brain and hypothalamus.
Obesity due to mutation in the MC4R gene is the most common cause of monogenic obesity. Patients have early-onset severe obesity and hyperphagia (Farooqi et al., 2003).
A condition characterized by a large capacity, thin-walled bladder and megaureter(s).
An inherited form of cystic kidney disease that leads to fibrosis and impaired renal function as a result of defects in the MUC1 gene, which encodes mucin 1.
An inherited form of cystic kidney disease leading to fibrosis and impaired renal function that is caused by mutations in the UMOD gene, which encodes uromodulin/Tamm-Horsfall mucoprotein.
An electrocardiographic tracing demonstrating sinus bradycardia, with a heart rate lower than an acceptable, predetermined threshold. Different thresholds, for rate and/or duration, may apply to different patient populations.
A benign mesenchymal neoplasm characterized by the presence of spindle shaped myofibroblasts and mast cells in a collagenous stroma. It is histologically identical to the myofibroblastoma of breast. It usually arises from the subcutaneous tissue and the most common sites of involvement are the inguinal/groin, paratesticular, and vulvovaginal areas.
A giant cell tumor that arises from the bone and is characterized by the presence of a malignant cellular component.
A malignant myoepithelioma characterized by the presence of a minor ductal component.
Hypertensive nephropathy secondary to malignant hypertension.
A fibrohistiocytic neoplasm that metastasizes to other anatomic sites.
A major decrease in signs of cancer, supported by pathological examination and based on pre-defined thresholds.
A vaccine containing synthetic multiple antigenic glycopeptide (MAG) composed of tri Tn glycotope (MAG-Tn3), which is comprised of a dendrimeric, nonimmunogenic lysine core linked to a tetravalent peptidic CD4+ T-cell epitope backbone and each attached to three Tn antigens (tri-Tn cluster), combined with the immunoadjuvant AS15, with potential antineoplastic activity. Upon administration of the MAG-Tn3/AS15 vaccine, MAG-Tn3 induces the production of tumor-specific anti-Tn glycosidic antibodies, which results in antibody-dependent cell cytotoxicity (ADCC) against Tn-expressing tumor cells. The Tn carbohydrate antigen, a tumor-associated antigen (TAA), is overexpressed in a number of tumor cell types. The tri-Tn clusters mimic carbohydrate structures found on tumor cells. The T-cell epitope stimulates effective T-cell responses. AS15, a potent adjuvant liposomal formulation that contains CpG 7909, monophosphoryl lipid (MPL), and QS-21, increases the immune response against the Tn antigens.
An autoimmune condition affecting the posterior pituitary gland, which is characterized by lymphocytic infiltration, and which often presents as diabetes insipidus.
An exacerbation of the chronic disease lupus.
An undifferentiated high grade pleomorphic sarcoma of bone that occurs in childhood and has not spread to other anatomic sites.
An undifferentiated high grade pleomorphic sarcoma of bone that occurs in adulthood and has not spread to other anatomic sites.
Kidney damage resulting from lithium which may include distal or collecting tubular cysts, proteinuria, interstitial nephritis and nephrogenic diabetes insipidus.
Interstitial nephritis due to Leptospira, which may be associated with non-oliguric acute kidney injury.
A rare leiomyosarcoma that arises from the deep soft tissue in the retroperitoneum or abdominal cavity.
The minimum rate of positive pressure (systolic) change within the left ventricle during a unit time.
The maximum rate of positive pressure (systolic) change within the left ventricle during a unit time.
The maximum rate of negative pressure (diastolic) change within the left ventricle during a unit time.
Delivery of a dead fetus greater than 28 weeks gestational age and/or greater than 1,000 grams birth weight.
Clinical and/or laboratory evidence of late reemergence of a disorder after a period of remission.
Clinical and/or laboratory evidence of reemergence of acute myeloid leukemia greater than or equal to 12 months from diagnosis.
Clinical and/or laboratory evidence of reemergence of acute lymphoblastic leukemia greater than or equal to 18 months (extramedullary) or 36 months (marrow) from diagnosis.
Chromosomal breakage that generates 10 Mb or larger fragments. The quantification of these breaks can be used as a surrogate measure for genomic instability, which may be caused by mutation of DNA repair genes, including BRCA1 or BRCA2.
A capsule containing a strain of the probiotic bacterium Lactobacillus with potential antimicrobial and immunomodulatory activities. As a dietary supplement, Lactobacillus, a naturally-occurring bacteria, may improve digestion and help maintain adequate colonization of the gastrointestinal (GI) tract by modulating the composition of the normal microflora. Because it produces lactic acid and hydrogen peroxide and other substances during fermentation, this bacterium creates an acidic environment that is unfavorable for pathogens. In addition, during colonization of the GI tract, this bacterium adheres to human epithelial cells and forms a protective barrier, thereby preventing the attachment of pathogens. Dietary supplementation with this bacterium has been shown to enhance innate and acquired immunity.
An adenoma of the anterior lobe of the pituitary gland that produces luteinizing hormone (LH).
A surgically created external opening into the jejunum.
An osteoma that develops on the surface of the bone.
Disease that is characterised clinically by neonatal hyperpigmentation, hypoglycaemia, failure to thrive, and recurrent infections and biochemically by glucocorticoid deficiency without mineralocorticoid deficiency. The disease usually presents in infancy or early childhood. Hypoglycaemic crises resulting in convulsions can lead to coma or death if untreated and recurrent hypoglycaemia may lead to neurological sequelae. Most cases are caused by defects in the adrenocorticotropin receptor, or its signalling pathway resulting in a failure of the cells of zona fasciculata in the adrenal cortex to respond appropriately to adrenocorticotrophic hormone, leading to a glucocorticoid deficiency. These defects are most commonly caused by mutations in MC2R (18p11.2) and MRAP (21q22.1). Other mutations reported include MCM4 (8q12-q13), NNT (5p12) and TXNRD2 (22q11.21). Inherited in an autosomal recessive manner.
A morphologic finding indicating the presence of an invasive component of carcinoma cells that measures more than 5 mm in greatest dimension.
A soft tissue tumor of uncertain differentiation which is locally aggressive but rarely metastasizes.
A non-metastasizing, locally aggressive, bone-forming neoplasm.
A benign but locally aggressive giant cell tumor that arises from the bone.
A locally aggressive or rarely metastasizing cartilaginous matrix-producing neoplasm characterized by the presence of neoplastic chondrocytes.
A locally aggressive or rarely metastasizing neoplasm that arises from the bone.
Narrowing of the infundibulum to the calyx, which produces an impediment to urine flow.
An infiltrating lipoma that affects skeletal muscle. It has a higher rate of local recurrence.
A benign or malignant lesion that occurs in infancy.
An acute lymphoblastic or acute myeloid leukemia that occurs in infancy.
An acute lymphoblastic leukemia that occurs in infancy.
An acute lymphoblastic leukemia without rearrangement of the KMT2A gene that occurs in infancy.
An acute lymphoblastic leukemia with rearrangement of the MLL gene that occurs in infancy.
Death of the patient due to the toxic side effects of induction therapy.
The disappearance of all signs of cancer, supported by the absence of phenotypically aberrant plasma cells (clonal) in bone marrow. (Rajkumar SV, Harousseau J, Durie B et al, Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011; 117(18):4691-4695)
A surgically created external opening into the ileum.
A condition characterized by deposition of IgM antibody in the glomerulus.
IgA nephropathy co-occurring with infectious disease.
Necrosis of the renal papillae, for which no underlying cause has been identified.
Obesity resulting from medical treatment or intervention.
A peptide vaccine consisting of a 20-mer peptide derived from isocitrate dehydrogenase type 1 (IDH1) containing the point mutation R132H (IDH1R132H), with potential antineoplastic activity. Upon subcutaneous vaccination with the IDH1R132H mutation-targeting IDH1 peptide vaccine, the vaccine stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells that express the IDH1R132H protein. R132H is a point mutation, which contains an amino acid substitution where arginine is replaced by histidine at position 132 of IDH1, and is highly expressed in gliomas as well as other tumor types; this mutation is associated with increased production of the oncometabolite R-2-hydroxyglutarate (2HG).
Myelodysplastic syndrome characterized by decreased cellularity in the bone marrow.
A finding of both hypertrophy and karyomegaly in the same lesion.
A finding of both hypertrophy and hyperplasia in the same lesion.
A finding of both hyperplastic and metaplastic changes in a pathologic process.
Abnormally high level of lactate in the blood.
A humanized monoclonal antibody directed against the human tumor-associated antigen GD2, with potential antineoplastic activity. Upon vaccination, the humanized monoclonal antibody 3F8 stimulates antibody-dependent cell-mediated cytotoxicity (ADCC) against GD2-expressing tumor cells. GD2, a disialoganglioside with expression in normal tissues restricted primarily to the cerebellum and peripheral nerves, is commonly expressed at high levels on tumors of neuroectodermal origins such as melanomas and neuroblastomas. Compared to the murine monoclonal antibody 3F8 (m3F8), the humanized form does not cause a human anti-mouse antibody (HAMA) response and shows enhanced ADCC activity.
A continuous, ambulatory electrocardiographic recording during which one or more electrodes are disconnected, at least temporarily, resulting in one or more invalid ECG waveforms.
A congenital abnormality found in Fisher 344 rats characterized by grossly visible nodule(s) usually located on the median lobe of the liver.
An assessment of the diffusion capacity of the lungs for carbon monoxide adjusted for hemoglobin concentration.
The diffusion capacity of the lungs for carbon monoxide adjusted for the ratio of hemoglobin concentration to alveolar volume.
An evaluation of the hematologic response of the disease to the therapy.
An improvement of platelet count as a response to treatment.
An improvement in erythrocyte count as a response to treatment.
A high-grade chondrosarcoma characterized by the presence of higher cellularity and a greater degree of nuclear atypia and pleomorphism as compared to grade II chondrosarcoma. Mitotic figures are easily detected.
An intermediate-grade chondrosarcoma characterized by the presence of increased cellularity and a greater degree of nuclear atypia and hyperchromasia as compared to grade I chondrosarcoma. Mitotic figures can be detected.
A term that refers to germinoma, seminoma, or dysgerminoma.
A finding of both germ cell depletion and germ cell degeneration.
Disturbance of cellular integrity and deterioration of germ cells.
A rhabdomyosarcoma characterized by the presence of chromosomal translocation t(1;13)(p36;q14) that results in PAX7-FOXO1 gene fusion; or translocation t(2;13)(q35;q14) that results in PAX3-FOXO1 gene fusion.
An alveolar rhabdomyosarcoma characterized by the presence of chromosomal translocation t(1;13)(p36;q14) that results in PAX7-FOXO1 gene fusion; or translocation t(2;13)(q35;q14) that results in PAX3-FOXO1 gene fusion. Approximately 80% of alveolar rhabdomyosarcomas are fusion-positive.
A rhabdomyosarcoma characterized by the absence of chromosomal translocation t(1;13)(p36;q14) or t(2;13)(q35;q14) and therefore the absence of PAX7-FOXO1 or PAX3-FOXO1 gene fusion.
An alveolar rhabdomyosarcoma characterized by the absence of chromosomal translocation t(1;13)(p36;q14) or t(2;13)(q35;q14) and therefore the absence of PAX7-FOXO1 or PAX3-FOXO1 gene fusion.
A pituitary gland microadenoma associated with a hormonal syndrome.
A pituitary gland macroadenoma associated with a hormonal syndrome.
Fucosylated, human umbilical cord blood (UCB)-derived regulatory T-cells (Tregs), with potential immunomodulating activity. Ex vivo, Tregs are isolated from cord blood, expanded, and fucosylated. Upon infusion, the fucosylated UCB Tregs modulate immune responses and induce tolerance to allogeneic transplants, such as hematopoietic stem cell transplants (HSCTs). This suppresses graft-versus-host disease (GVHD). Fucosylation improves the activity of Tregs and reduces the amount of Tregs that need to be expanded and infused.
An electrocardiographic tracing demonstrating frequent premature atrial contractions that exceed an acceptable, predetermined threshold. Different thresholds may apply to different patient populations.
A calculated ratio of the forced expiratory volume in one second to the largest observed expired volume during the first six seconds of a forced vital capacity (FVC) maneuver.
Reduced or absent function of the receptor for follicle stimulating hormone associated with a mutation in the FSHR gene.
A variant of FSGS characterized by scarring of the glomerulus adjacent to the origin of the proximal convoluted tubule; this occurs in the absence of collapsing and perihilar FSGS. (D'Agati VD, et al. ""Pathologic Classification of Focal Segmental Glomerulosclerosis: A Working Proposal."" Am J Kidney Dis 43.2 (2004): 368-82.)
A variant of FSGS characterized by scarring of the glomerulus where at least 50% of the scars are adjacent to the hilum and must have hyalinosis; this excludes cellular, tip and collapsing FSGS. (D'Agati VD, et al. ""Pathologic Classification of Focal Segmental Glomerulosclerosis: A Working Proposal."" Am J Kidney Dis 43.2 (2004): 368-82.)
A variant of FSGS characterized by glomerular tuft collapse, which may result in scarring. (D'Agati VD, et al. ""Pathologic Classification of Focal Segmental Glomerulosclerosis: A Working Proposal."" Am J Kidney Dis 43.2 (2004): 368-82.)
A variant of FSGS characterized by hypercellularity of the glomerulus; this excludes the tip and collapsing FSGS. (D'Agati VD, et al. ""Pathologic Classification of Focal Segmental Glomerulosclerosis: A Working Proposal."" Am J Kidney Dis 43.2 (2004): 368-82.)
The reemergence of a disorder as diagnosed by clinical and/or laboratory evidence following a single documented period of remission.
No new lesions(s) and a decrease in tumor size, or a reduction in central necrosis or attenuation in one or more enhancing lesions, based on pre-defined thresholds.
Early development of isosexual secondary characteristics in boys, due to autosomal dominant mutations in the LHCGR gene.
Hemolytic uremic syndrome associated with an inherited defect, but which is not associated with shiga toxin-producing enterobacteria.
An adenoma of the anterior lobe of the pituitary gland that produces follicle-stimulating hormone (FSH).
Birth when a fetus is less than 28 weeks gestational age.
A finding indicating the involvement of sites other than the bone marrow by a hematopoietic neoplasm.
A mouthwash containing ethyl alcohol, with topical antibacterial activity. Upon rinsing the oral cavity with the ethyl alcohol mouthwash, ethyl alcohol denatures bacterial proteins, and dissolves and disrupts the bacterial lipid membrane, thereby killing the bacteria. This reduces oral colonization with harmful bacteria and may prevent oral mucositis.
A finding of both erosion and ulceration in the same lesion.
An orally available, gluten-free, enzymatically hydrolyzed cysteine-rich whey-protein based nutritional supplement containing essential vitamins, minerals, and trace elements, as well as fat and carbohydrates. Upon oral intake of the nutritional supplement, the whey protein may improve gastric functioning and gastrointestinal health, thereby reducing vomiting and diarrhea. The whey-based hydrolyzed protein helps to alleviate the digestive burden for the pancreas and may be beneficial for patients with a pancreas-associated disease, such as pancreatitis or pancreatic cancer. Due to the high levels of cysteine in the whey protein, this supplement increases levels of the antioxidant glutathione (GSH). The polyunsaturated fatty acids in this supplement are incorporated in cell membranes and affect the production of pro-inflammatory mediators, eliciting an anti-inflammatory effect. Medium chain triglycerides (MCT) in this supplement enhance fat absorption and may aid in the prevention of fat malabsorption. Altogether, this supplement may prevent both malnutrition and weight loss.
A surgically created external opening into the intestine.
A composite lung function endpoint that is composed of peak inspiratory and peak expiratory flows, expiration time, and relaxation time, is used to measure the occurrence and prolongation of apnea periods, and is scaled to inspiratory/expiratory strength to account for breathing variability.
The period of time between the end of inhalation and the active start of expiration.
The period of time between the end of exhalation and the active start of inspiration.
A mouth rinse containing 0.25% East Indian sandalwood oil, which is derived from the heartwood of Santalum album, a tree native to southern Asia, with potential anti-inflammatory, anti-infective and anti-mucositis activities. East Indian sandalwood oil (EISO) is primarily comprised of the sesquiterpene alcohols alpha- and beta-santalol. Although the exact mechanisms of action through which EISO exerts its effects have yet to be fully elucidated, upon rinsing the oral cavity with the EISO mouth rinse, the active ingredients in the oil may inhibit the production of pro-inflammatory cytokines and chemokines, most likely through the inhibition of the activity of key inflammatory enzymes, including the cyclooxygenases. This prevents inflammation of the mucosal membranes and may prevent or decrease chemotherapy- and/or radiation-induced oral mucositis.
Delivery of a dead fetus greater than 22 weeks but less than 28 weeks gestational age, and/or whose birth weight is greater than 500 grams but less than 1,000 grams.
Clinical and/or laboratory evidence of early reemergence of a disorder after a period of remission.
Clinical and/or laboratory evidence of reemergence of acute lymphoblastic leukemia less than 18 months (extramedullary) or 36 months (marrow) from diagnosis.
Expression of fusion protein EWSR1-CREB1 resulting from a t(2;22)(q33;q12). It is present in the vast majority of angiomatoid fibrous histiocytoma cases.
Fecal constipation or impaction resulting in bowel and bladder dysfunction.
A monoclonal antibody directed against B7H1 (B7 homolog 1; programmed cell death ligand 1) with potential immunostimulating activity. Upon intravenous administration, durvalumab binds to the cell surface antigen B7H1, thereby blocking B7H1 signaling. This may activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against B7H1-expressing tumor cells. B7H1, a member of the B7 protein superfamily and a negative regulator of cytokine synthesis, is overexpressed on certain tumor cell types.
A surgically created external opening into the duodenum.
An immunoglobulin (Ig) G1 monoclonal antibody directed against both human epidermal growth factor receptor 3 (HER3 or ERBB3) and human epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Duligotuzumab binds to both EGFR and HER3 and inhibits their activation. This may prevent EGFR/HER3-mediated signaling and inhibit EGFR/HER3-dependent tumor cell proliferation. In addition, MEHD7945A induces antibody-dependent cell-mediated cytotoxicity (ADCC) against EGR/HER3-expressing tumor cells. EGFR and HER3, members of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, are frequently overexpressed in tumors; their expression is associated with both poor prognosis and drug resistance.
Thyroid peroxidase system defect due to presumed mutation(s) in the DUOX2 gene, resulting in decreased activity of dual oxidase 2.
A rare, progressive disorder characterized by abnormally high blood pressure in the pulmonary artery caused by obstruction and obliteration of the small pulmonary arteries due to drugs or toxins. The stimulant appetite suppressant aminorex fumarate and other stimulant anorectics such as the serotonin reuptake inhibitor dexfenfluramine, as well as other agents, including illegal substances have been reported as causative agents.
The loss of tension or continuity of sutures.
An enzyme deficiency in the androgen biosynthesis pathway, resulting in the underproduction of one or more androgens by the adrenal glands and/or gonads.
A catheter that has moved from its intended location.
A conversion from one disease diagnosis to another, which may be considered a progression to a worsening state.
The calculated ratio of the lung's alveolar volume with respect to its diffusion capacity for carbon monoxide.
Glomerulonephritis characterized by endocapillary proliferation and the presence of inflammatory cells affecting 50% or more of all glomeruli.
A response indicating that an individual has not done something in the past 7 days.
A topical patch containing the epolamine salt form of the nonsteroid anti-inflammatory drug (NSAID) diclofenac, with anti-inflammatory, anti-pyretic and analgesic activities. Upon topical application of the diclofenac epolamine patch to a specific area, the patch releases diclofenac epolamine into the skin. Diclofenac locally binds to cyclooxygenase isoforms 1 and 2 (COX-1 and -2). The inhibition of COX-2 by diclofenac prevents the COX-2-mediated synthesis of proprostaglandins (PGs) and thereby locally relieves PG-mediated pain, fever and inflammation.
Condition comprising congenital nephrotic syndrome with associated WT1 gene mutation with either intersex disorder or Wilms tumor.
A finding that generally has features of degeneration and regeneration.
A finding that generally has features of degeneration and atrophy.
An electrocardiographic tracing that is generated by cardioversion or defibrillation.
Circumscribed morphea in which the lesions are found in the deep dermis, panniculus, fascia, or superficial muscle.
The loss of elasticity of the bladder wall with increased urine volume.
An orally available agent that may prevent the formation of gallstones.
Decreased activity of the nuclear receptor protein DAX1, caused by mutation(s) in the NR0B1 gene (on the X chromosome), resulting in adrenal hypoplasia congenita that may be associated with hypogonadotropic hypogonadism.
An evaluation of the cytogenetic response of the disease to the therapy.
A partial decrease in abnormal karyotype, based on pre-defined thresholds.
No change in abnormal karyotype, based on pre-defined thresholds.
A minor decrease in abnormal karyotype, based on pre-defined thresholds.
A minimal decrease in abnormal karyotype, based on pre-defined thresholds.
A surgically created external opening into the anterior wall of the bladder.
A proprietary topical gel formulation containing an extract of curcumin, the polyphenol derived from the plant Curcuma longa, with potential anti-inflammatory, antioxidant, and wound healing activities. Upon topical administration to the affected areas, curcumin inhibits a variety of pro-inflammatory enzymes and reduces the production of certain pro-inflammatory mediators. Curcumin also blocks the formation of reactive oxygen species (ROS), neutralizes free radicals and prevents oxidative stress and DNA damage. In addition, curcumin inhibits phosphorylase kinase (PhK) in the skin, which prevents multiple PhK-mediated signal transduction pathways that are induced upon skin injury. This further prevents inflammation, promotes healing and reduces scar tissue formation. The proprietary curcumin-based gel also provides moisture to the skin and contains tetrahydropiperine (THP), which is derived from black pepper fruit and increases skin uptake of curcumin.
Cryoglobulinemia glomerulonephritis associated with chronic disease, often inflammatory conditions.
A common, usually encapsulated benign nerve sheath tumor composed of well-differentiated Schwann cells.
Kidney damage resulting from exposure to contrast agents.
Neurogenic bladder, the cause of which is present at birth.
Nephrotic syndrome associated with syphilis, most commonly presenting in the first three months of life.
Nephrotic syndrome associated with toxoplasmosis, most commonly presenting in the first three months of life.
Nephrotic syndrome associated with rubella, most commonly presenting in the first three months of life.
Nephrotic syndrome presenting within the first three months of life, and which is associated with an infectious process.
Nephrotic syndrome within the first three months of life, characterized by scarring of the glomerulus, in which only part of the glomerulus is involved, and less than 50% of the glomeruli are affected.
Nephrotic syndrome associated with a cytomegalovirus infection, most commonly presenting in the first three months of life.
Thyroid stimulating hormone (TSH) deficiency associated with mutations(s) in the TSHB gene that encodes thyrotropin subunit beta.
Adrenocorticotropic hormone (ACTH) deficiency due to mutation(s) in the TBX19 gene.
The disappearance of all signs of cancer, based on CT scan and criteria-defined assessments.
Inflammation of the colon resulting from Clostridium Sordelli.
A probiotic containing the anaerobic, butyric acid-forming Gram-positive bacterium Clostridium butyricum (C. butyricum), with potential immunomodulatory activity. Upon oral administration of C. butyricum-containing probiotic, C. butyricum modulates the composition of the normal gastrointestinal (GI) microflora and help maintain adequate colonization of the GI tract, thereby improving digestion and preventing GI disturbances. This bacterium creates an environment unfavorable to pathogens by adhering to human epithelial cells, thereby forming a protective mucosal barrier. This prevents attachment of pathogens and reduces the risk of infection. Dietary supplementation with this bacterium may restore or enhance intestinal immunity.
An evaluation of the clinical response of the disease to the therapy.
Any clinical change to a subject as determined by a non-invasive imaging procedure.
A spontaneous, age-related renal disease of rats, characterized by morphological changes such as degeneration of the epithelium lining of the tubules, thickening of glomerular, Bowman and proximal tubular basement membranes, and lesions in the glomeruli leading to mesangial overload and glomerulosclerosis.
A mouthwash containing the biguanide chlorhexidine and ethyl alcohol, with topical antibacterial activity. Upon rinsing the oral cavity with the chlorhexidine/ethyl alcohol mouthwash, the positively charged chlorhexidine cation exerts its antibacterial activity through binding to the negatively charged microbial cell surface, which destroys the integrity of the cell membrane. This causes leakage of intracellular components leading to cell death. Ethyl alcohol denatures bacterial proteins, and dissolves and disrupts the bacterial lipid membrane, thereby killing the bacteria. This reduces oral colonization with harmful bacteria and may prevent oral mucositis.
A spindle cell rhabdomyosarcoma occurring in children.
A periosteal osteosarcoma occurring in childhood.
Lymphomatoid granulomatosis that occurs during childhood.
Langerhans cell histiocytosis that occurs during childhood and does not involve the bone marrow, spleen, liver, or lung.
Langerhans cell histiocytosis that occurs during childhood and involves the bone marrow, spleen, liver, or lung.
An extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue that occurs during childhood.
An acute myeloid leukemia that occurs in childhood and is characterized by the rearrangement of the NUP98 gene.
A rare acute myeloid leukemia that occurs in childhood and is characterized by deletion of chromosome 7.
A rare acute myeloid leukemia that occurs in childhood and is characterized primarily by deletions of 5q.
Acute myeloid leukemias that occur in childhood and do not fulfill the criteria for inclusion in the group of acute myeloid leukemias which have recurrent genetic abnormalities or myelodysplastic changes, or are therapy-related. This category includes entities classified according to the French-American-British classification scheme.
Kidney damage resulting from exposure to chemotherapeutic drugs.
Inflammation associated with the use of a catheter.
A radioconjugate composed of vemurafenib, an ATP-competitive, small-molecule inhibitor of BRAF(V600E) kinase, labeled with the radioisotope carbon C 14, with potential use for evaluating the pharmacokinetic profile of vemurafenib. Vemurafenib selectively binds to the ATP-binding site of BRAF(V600E) kinase and inhibits its activity, which may result in both an inhibition of an over-activated MAPK signaling pathway in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. Labeling of vemurafenib with the radioactive tracer carbon C 14 allows for the evaluation of vemurafenib's pharmacokinetic profile, including its absorption, distribution, metabolism, and excretion (ADME). The BRAF(V600E) gene mutation in which valine is substituted for glutamic acid at residue 600 (V600E), is found in many cancer cell types and plays a key role in the over-activation of the MAPK signaling pathway.
An orally bioavailable radioconjugate composed of roniciclib, a cyclin dependent kinase (CDK) inhibitor, radiolabeled with carbon C 14, with potential use for evaluating the pharmacokinetic profile of roniciclib. Roniciclib selectively binds to and inhibits the activity of various CDK subtypes, which leads to cell cycle arrest and an inhibition of tumor cell proliferation. Labeling of roniciclib with the radioactive tracer carbon C 14 allows for the evaluation of roniciclib's pharmacokinetic profile, including its absorption, distribution, metabolism, and excretion (ADME). CDKs, serine/threonine kinases overexpressed in various tumor cell types, play key roles in the regulation of both cell cycle progression and cellular proliferation.
A radioconjugate composed of gilteritinib, an inhibitor of the receptor tyrosine kinases (RTKs) FMS-related tyrosine kinase 3 (FLT3, STK1, or FLK2), AXL (UFO or JTK11) and anaplastic lymphoma kinase (ALK or CD246), labeled with the radioisotope carbon C 14, with potential use for evaluating the pharmacokinetic profile of gilteritinib. Gilteritinib binds to and inhibits both the wild-type and mutated forms of FLT3, AXL and ALK. This may result in an inhibition of FLT3, AXL, and ALK-mediated signal transduction pathways and the reduction of tumor cell proliferation in cancers that overexpress these RTKs. Labeling of gilteritinib with the radioactive tracer carbon C 14 allows for the evaluation of gilteritinib's pharmacokinetic profile, including its absorption, distribution, metabolism, and excretion (ADME).
A radiotracer consisting of sarcosine, the N-methyl derivative of the amino acid glycine, labeled with the positron-emitting isotope carbon C 11, that can be used for tumor imaging upon positron emission tomography/computed tomography (PET/CT). Upon administration, C-11 sarcosine is taken up by and accumulates in tumor cells, thereby allowing tumor imaging with PET/CT. Sarcosine, a non-proteinogenic amino acid and oncometabolite, is elevated in certain tumor cell types. Its expression seems to correlate with increased tumor invasiveness.
A sustained-release (SR), oil-based oral capsule composed of a cannabis extract, which contains a variety of cannabinoids but is comprised mainly of tetrahydrocannabinol (THC), with potential anti-cachexic and analgesic activities. Upon oral administration, the cannabinoids bind to the cannabinoid G-protein coupled receptor CB1, which is located in both central and peripheral neurons; CB1 receptor activation inhibits adenyl cyclase, increases various signal transduction pathways, and modulates the activity of various ion channels. This provides an analgesic effect, increases appetite, decreases chemotherapy-induced nausea and vomiting, and improves weight gain. The formulation allows for the immediate release of cannabinoids and quick onset of action, which is followed by a gradual release of cannabinoids. The SR form facilitates longer lasting therapeutic effects and causes fewer psychoactive side effects when compared to non-SR cannabinoid-containing oral formulations.
Hemangiosarcoma occurring in a dog. It is an incurable tumor of vascular endothelial cells and occurs more commonly in dogs beyond middle age, and is especially common in certain breeds. Most hemangiosarcomas do not have a known cause.
The amount of cancer antigen 125 is reduced by 75% from protocol-defined baseline value(s).
The amount of cancer antigen 125 is reduced by 50% from protocol-defined baseline value(s).
Expression of a fusion protein that results from a t(11;16)(q13;p13) translocation, which involves the human genes C11orf95 and MKL2.
Presumed deficiency of brain-derived neurotropic factor (BDNF), associated with loss-of-function mutation(s) in the BDNF gene.
A non-invasive serous neoplasm that arises from the ovary and shows micropapillary and/or cribriform architectural patterns. It is composed of round epithelial cells with scant cytoplasm and moderate nuclear atypia.
A group of lesions that affect the bone and have the appearance and cytogenetic or molecular characteristics of neoplasms but the clinical behavior is suggestive of a non-neoplastic process.
A finding indicating the involvement of the bone marrow and other anatomic sites, which may include the peripheral blood, lymph nodes, and/or extranodal sites, by a hematopoietic neoplasm.
A low-grade malignant blood vessel neoplasm arising from the bone. It is characterized by the presence of epithelioid endothelial cells. The neoplastic cells are arranged in cords and nests, which are embedded in a myxoid to hyalinized stroma.
Non-coordinated, reflexive contraction of the bladder and sphincter relaxation.
A concentrated fruit juice containing black raspberries, with potential antioxidant, pro-apoptotic, anti-angiogenic and chemopreventive activities. In addition to vitamins, minerals and phytosterols, black raspberries are rich in phenolic acids, such as gallic acid, ellagic acid, anthocyanidins, and flavonoids. Upon oral administration, the phytochemicals in the black raspberry nectar inhibit the activation of several signal transduction pathways involved in carcinogenesis and the expression of downstream target genes that are upregulated in a variety of cancer cell types. In addition, the phytochemicals in black raspberry may protect the oral microbiome and may enhance the bacterial defense against pathogens.
Kidney damage resulting from exposure to bisphosphonates.
A biologic used to alter the progression of autoimmune disease.
A molecular abnormality indicating the presence of rearrangement mutations in either the BRCA1 gene at 17q21 or the BRCA2 gene at 13q12.3.
A human immunoglobulin G1 (IgG1) monoclonal antibody directed against the human immunosuppressive ligand programmed death-ligand 1 (PD-L1) protein, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, avelumab binds to PD-L1 and prevents the interaction of PD-L1 with its receptor programmed cell death protein 1 (PD-1). This inhibits the activation of PD-1 and its downstream signaling pathways. This may restore immune function through the activation of cytotoxic T-lymphocytes (CTLs) targeted to PD-L1-overexpressing tumor cells. In addition, avelumab induces an antibody-dependent cellular cytotoxic (ADCC) response against PD-L1-expressing tumor cells. PD-1, a cell surface receptor belonging to the immunoglobulin superfamily expressed on T-cells, negatively regulates T-cell activation and effector function when activated by its ligand, and plays an important role in tumor evasion from host immunity. PD-L1, a transmembrane protein, is overexpressed on a variety of tumor cell types and is associated with poor prognosis.
Autologous, human CD8 T-lymphocytes, comprised of both central memory T-cells (Tcm) and nave T-cells (Tn), that are transduced, ex vivo, with a self-inactivating (SIN) lentiviral vector encoding a high-affinity T-cell receptor (TCRc4) specific for the human tumor antigen Wilms tumor 1 (WT1) epitope 126-134 (RMFPNAPYL), with potential antineoplastic activity. Upon isolation of peripheral blood lymphocytes (PBLs), transduction, expansion ex vivo, priming of the Tn subset, but not the Tcm subset, with interleukin-21 (IL-21) and reintroduction of equal amounts of Tcm and Tn cells into the patient, WT1-TCRc4 gene-transduced CD8-positive Tcm/Tn lymphocytes redirect T-lymphocytes to WT1-expressing tumor cells and specifically bind to and lyse those cells. This inhibits proliferation of WT1-expressing tumor cells. WT1 protein, a zinc finger DNA-binding transcriptional regulator, is overexpressed in most leukemias and various solid tumors, while expression in normal, healthy tissues is very limited; its expression is correlated with aggressiveness and poor prognosis.
An autologous cancer vaccine composed of oxidized ovarian tumor cell lysate, with potential immunostimulatory and antineoplastic activities. Upon administration, the autologous oxidized ovarian tumor cell lysate vaccine exposes the immune system to an undefined amount of tumor-associated antigens (TAAs), which may result in the induction of both anti-tumor cytotoxic T-lymphocytes (CTLs) and antibody-dependent responses against TAA-expressing cells, leading to tumor cell lysis. Compared to non-oxidized tumor cell lysate vaccines, oxidized tumor cell lysate vaccines induce necrotic cell death, increase the immunogenicity of the TAAs and may enhance the anti-tumor immune response.
A personalized cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with immunogenic peptides derived from autologous non-small cell lung cancer (NSCLC) cells, with potential immunostimulating and antineoplastic activities. During leukapheresis, mature DCs are loaded with autologous NSCLC-derived peptides. Upon re-administration of the NSCLC peptide-specific DC vaccine, the immune system is exposed to NSCLC-associated antigens. This results in the induction of a specific cytotoxic T-lymphocyte (CTL) response against NSCLC cells and tumor cell lysis.
A personalized, proprietary cancer vaccine composed of sterile, irradiated, non-dividing, live colon cancer cells obtained from an individual after tumor resection, with potential immunoactivating and antineoplastic activities. Upon intradermal administration, the autologous colon cancer cell vaccine activates the immune system and elicits a cytotoxic T-lymphocytic (CTL) response against the residual colon cancer cells, which results in tumor cell death. This may prevent cancer recurrence. According to the vaccination schedule, the first two out of the four doses are co-administered with the immunoadjuvant bacillus Calmette-Guerin (BCG), which is an attenuated strain of Mycobacterium bovis that non-specifically enhances the immune response.
Human autologous T-lymphocytes transduced with a retroviral vector encoding a T-cell receptor (TCR) specific for the cancer-testis antigens (CTAs) NY-ESO-1 and L antigen family member 1 (LAGE-1; Cancer/Testis Antigen 2; CTA2; CT2), with potential antineoplastic activity. Following leukapheresis, isolation of lymphocytes, expansion ex vivo, transduction, and reintroduction into the patient, the autologous anti-NY-ESO1/LAGE-1 TCR-transduced c259 T-lymphocytes specifically target and bind to NY-ESO-1/LAGE-1-overexpressing tumor cells. This may result in cytotoxic T-lymphocyte (CTL)-mediated elimination of NY-ESO-1/LAGE-1-positive cancer cells. NY-ESO-1 and LAGE-1, members of the cancer-testis antigen (CTA) family, are overexpressed on the surface of various tumor cell types.
Abnormally large, misshapen and/or clumped vacuoles containing cell debris in the testis, or present in stages of spermatogenesis when not normally seen.
A cancer vaccine comprised of a recombinant, attenuated, replication-defective simian adenovirus vector (ChAdOx1) encoding the human 5T4 fetal oncoprotein (ChAdOx1.5T4), with potential immuno-activating and antineoplastic activities. Upon administration of the recombinant attenuated chimpanzee adenovirus 5T4 vaccine, the viral vector expresses 5T4 and stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing 5T4, which results in tumor cell lysis. 5T4, a transmembrane glycoprotein, is overexpressed by a variety of cancer cell types; its expression is correlated with increased invasiveness.
A humanized, Fc optimized, monoclonal antibody directed against the protein ligand PD-L1 (programmed cell death-1 ligand 1), with potential immune checkpoint inhibitory and antineoplastic activities. Atezolizumab binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1) expressed on activated T-cells, which may enhance the T-cell-mediated immune response to neoplasms and reverse T-cell inactivation. In addition, by binding to PD-L1, MPDL3280A also prevents binding of this ligand to B7.1 expressed on activated T cells, which further enhances the T-cell-mediated immune response. PD-L1 is overexpressed on many human cancer cell types and on various tumor-infiltrating immune cells. PD-L1 binding to PD-1 on T-cells suppresses the immune system and results in increased immune evasion. PD-1, a transmembrane protein, is a negative regulator of the immune system that limits the expansion and survival of CD8+ T cells. The Fc region of MPDL3280A is modified in such a way that it does not induce either antibody-dependent cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC).
A condition in which a previously descended testicle permanently moves out of the scrotum.
A second-generation antisense oligonucleotide targeting heat shock protein 27 (Hsp27) with potential antitumor and chemosensitizing activities. Apatorsen suppresses tumor cell expression of Hsp27, which may induce tumor cell apoptosis and enhance tumor cell sensitivity to cytotoxic agents. Hsp27, a chaperone belonging to the small heat shock protein (sHsp) group of proteins, is a cytoprotective protein that supports cell survival under conditions of stress; it has been found to be over-expressed in a variety of human cancers.
Kidney damage resulting from exposure to antimicrobials.
Genetically modified, autologous T-lymphocytes transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) specific for mesothelin linked to the signaling domains for the co-stimulatory molecules CD28 and CD3 zeta, as well as the suicide gene inducible caspase 9 (iCasp9 or iC9), with potential immunomodulating and antineoplastic activities. Upon intravenous administration, anti-mesothelin iCasp9M28z CAR-transduced autologous T lymphocytes specifically target and kill mesothelin-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If the administered T-cells lead to unacceptable side effects, a dimerizing agent can be administered, which binds to the FKBP12-F36V drug-binding domain and activates caspase 9, resulting in the apoptosis of the administered T-cells. Mesothelin, a tumor-associated antigen, is overexpressed in a variety of cancer cell types.
Autologous human peripheral blood T-lymphocytes transduced with a lentiviral or retroviral vector encoding a human leukocyte antigen A2 (HLA-A2) restricted anti-cancer-testis antigen 1 (NY-ESO-1) T-cell receptor (TCR) gene, with potential antineoplastic activity. Following leukapheresis, isolation of lymphocytes, expansion ex vivo, transduction, and re-introduction into the patient, the anti-HLA-A2/NY-ESO-1 TCR-transduced autologous T lymphocytes recognize and bind to NY-ESO-1/HLA-A2-positive tumor cells. This results in cytotoxic T-lymphocyte (CTL)-mediated elimination of NY-ESO-1-positive cancer cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types.
A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for glypican-3 (GPC3), with potential immunostimulating and antineoplastic activities. Upon administration, anti-GPC3-CAR autologous T-lymphocytes specifically target and bind to GPC3-expressing tumor cells, resulting in tumor cell lysis. GPC3, a heparan sulfate proteoglycan and a member of the glypican family, is overexpressed on certain tumor cell types while minimally expressed in normal, healthy cells; GPC3 plays an important role in cellular proliferation and differentiation.
Autologous lymphocytes transduced with a retroviral vector encoding a chimeric antigen receptor (CAR) specific for the tumor-associated antigen human carcinoembryonic antigen (CEA), with potential immunostimulating and antineoplastic activities. Upon administration, the anti-CEA-CAR autologous T-lymphocytes target and bind to tumor cells expressing CEA, which results in the cytotoxic T-lymphocyte (CTL)-mediated cell killing of CEA-expressing tumor cells. CEA is overexpressed in various tumor cell types.
An Escherichia coli periplasm-expressed tetrameric fusion protein composed of four single-chain variable regions (scFv) of the murine immunoglobulin (Ig) G2a anti-CD20 monoclonal antibody B9E9 fused to the streptavidin (SA) gene of Streptomyces avidinii (scFv-SA), with potential use in pretargeted radioimmunotherapy (PRIT). Upon intravenous administration of the anti-CD20 B9E9 scFv-SA fusion protein, this agent targets and binds to CD20-expressing tumor cells. Subsequently, a biotinylated N-acetylgalactosamine-containing clearing agent is administered, which binds to the streptavidin moiety of the unbound fusion protein and promotes its hepatic excretion. In turn, radiolabeled DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-biotin is administered and, due to its small size, quickly distributes. The biotin moiety efficiently binds to the SA moiety of the bound fusion protein, which localizes the biotin-conjugated radionuclide to the tumor site. CD20, a tumor-associated antigen (TAA), is overexpressed on B-cell malignancies. PRIT increases both tumor uptake and renal elimination of the radionuclide conjugate as compared to conventional radioimmunotherapy (RIT), where the radioisotope is bound to the antibody before administration; this increases the dose of radionuclide delivered to the tumor while limiting radiation exposure for normal, healthy tissues.
A humanized version of the immunoglobulin (Ig) G1 monoclonal antibody Mik-Beta-1 (Hu-Mik-Beta-1) directed against CD122, the beta-subunit shared by the interleukin-2 (IL-2) and IL-15 receptor (IL-2/IL-15Rbeta). Upon intravenous infusion, Hu-Mik-Beta-1 binds to CD122 expressed on certain tumor cells. This blocks the binding of the inflammatory cytokines IL-2 and IL-15 to IL-2R and IL-15R, respectively, and prevents IL-2/IL-2R- and IL-15/IL-15R-mediated signaling. This may inhibit the proliferation of CD122-expressing tumor cells. In addition, blocking CD122 on T-lymphocytes prevents the over-activation of T-lymphocytes in various T-cell mediated autoimmune diseases, which is predominantly mediated by IL-15/IL-15R signaling. CD122, involved in both IL-2 and IL-15 signaling, is overexpressed on certain cancer cells, such as those found in T-cell large granular lymphocyte (T-LGL) leukemia.
An angiosarcoma that arises from the soft tissues, usually in the deep muscles of the lower extremities, retroperitoneum, mediastinum, and mesentery.
A morphologic variant of embryonal rhabdomyosarcoma. It is characterized by the presence of large hyperchromatic and anaplastic cells.
Increase in eosinophilic cytoplasmic droplets of alpha 2u-globulin in the S2 segment of the proximal tubules in the cortex with exfoliation of cells, an increase in mitotic figures in affected portions of the proximal tubules, tubular basophilia in some cases, and formation of granular casts at the junction of the inner and outer stripes of the medulla. (INHAND)
An orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. Alpelisib specifically inhibits PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis. Dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.
Human leukocyte antigen (HLA)-haploidentical donor-derived natural killer (NK) cells that are activated with the cytokine interleukin-15 (IL-15), with immunomodulating and antineoplastic activities. Upon leukapheresis, the HLA-haploidentical donor peripheral blood mononuclear cells (PBMCs) are treated to remove T-lymphocytes (CD3+) and B-lymphocytes (CD19+) cells. In turn, NK cells are expanded and activated with IL-15. Upon infusion of the allogeneic CD3- CD19- selected NK cells, these cells recognize and bind to tumor cells, and secrete perforins, granzymes, and cytokines, which results in cancer cell lysis.
Allogeneic cytotoxic T-lymphocytes (CTLs) that are specifically reactive to BK virus (BKV), with potential antiviral activity. Upon infusion of allogeneic BK-specific CTLs into immunocompromised patients who were infected with BKV after allogeneic stem cell transplantation, these cells exert a specific CTL response against BKV, thereby killing and eliminating the BKV-infected cells. BKV is a member of the polyomavirus family that may cause mild symptoms in normal, healthy people; however, BKV infection can lead to severe disease in immunocompromised patients.
Autologous tumor infiltrating lymphocytes (TILs) harvested directly from the infiltrate of a patient's tumor and treated with an inhibitor of the serine/threonine kinases Akt-1 and -2 (Akti-1/2) during ex vivo expansion, with potential antineoplastic activity. Upon reintroduction into the patient, the Akti-1/2-treated TILs recognize and kill cancer cells. Akt inhibition promotes the immunologic memory of the TILs and enhances their expansion, in vivo long-term persistence and antitumor activity.
The inhibition of normal respiration by physical obstruction(s) to the airway.
A benign mesenchymal neoplasm arising from skeletal muscle and occurring in adults.
A finding of dysplasia in the adnexal appendages.
An acute myeloid leukemia in infancy characterized by t(7;12)(q36;p13) and fusion of the homeobox gene HLXB9 (MNX1) with the ETV6 gene.
Acute myeloid leukemia with the variant RARA t(5;17)(q35;q21) and the expression of NPM1-RARA fusion protein.
An acute myeloid leukemia associated with t(3;3)(q21.3;q26.2) resulting in the reposition of a distal GATA2 enhancer to activate MECOM expression. It may present de novo or follow a myelodysplastic syndrome. The clinical course is aggressive.
Acute myeloid leukemia with the variant RARA t(17;17)(q21;q21) and the expression of STAT5B-RARA fusion protein.
Unique gene expression-based patient cluster groups in high-risk B-precursor acute lymphoblastic leukemia determined by Recognition of Outliers by Sampling Ends (ROSE).
Gene expression-based patient cluster groups in acute lymphoblastic leukemia.
A benign fibroblastic neoplasm that arises from acral sites, usually the periungual area of the digits. It is characterized by the proliferation of spindled and stellate-shaped fibroblasts in the dermis in a myxoid or collagenous stroma. Nuclear atypia is usually minimal. It usually presents as a solitary and slow-growing dome-shaped mass on a digit. The recurrence rate is low.
Neurogenic bladder, the cause of which is not present at birth.
Hypogonadotropic hypogonadism, the cause of which is not present from birth.
An infection with the Cytomegalovirus that is not present from birth.
Central hypothyroidism, the cause of which is not present at birth.
Adrenocorticotropic hormone (ACTH) deficiency, the cause of which is not present at birth.
A state characterized by the gradual increase in entities or substances.
A supernumerary tissue in addition to normal tissues.
The absence of change in the overall attenuation of the metastasis and in the peripheral rim, suggesting a lack of response to treatment.
A molecule with potential antineoplastic activity. Upon oral administration, ASP4132 affects oxidative phosphorylation in mitochondria of metabolically-active tumor cells, which reduces both energy production and tumor cell proliferation. Mitochondrial oxidative phosphorylation is hyperactivated in tumor cells and plays a key role in the promotion of tumor cell proliferation.
An intravenously-administered agent capable of modulating the activity of epidermal growth factor receptor (EGFR), with potential antineoplastic activity.
Antenatal hydronephrosis with the following clinical findings: 1) an anterior-posterior renal pelvis diameter (APRPD) of greater than or equal to 7mm at less than 28 weeks, 2) greater than or equal to10 mm at greater than or equal to 28 weeks, or 3) any one of the following findings: a)dilation of peripheral calyces, b) abnormal parenchymal thickness or appearance, c) visibly dilated ureter, d) an abnormal bladder, or e) the presence of oligohydramnios suspected to be related to the urinary tract. (Adapted from: Hiep T. Nguyen, Carol B. Benson, Bryann Bromley, Jeffrey B. Campbell, Jeanne Chow, Beverly Coleman, Christopher Cooper, Jude Crino, Kassa Darge, C.D. Anthony Herndon, Anthony O. Odibo, Michael J.G. Somers, Deborah R. Stein; Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system); Pediatric Urology; December 2014 Volume 10, Issue 6, Pages 982-998)
Antenatal hydronephrosis with the following clinical findings: 1) an anterior-posterior renal pelvis diameter (APRPD) of 4 to less than 7 mm at less than 28 weeks, 2) to less than10 mm at greater than or equal to 28 weeks, and 3) may have central calyceal dilation. (Adapted from: Hiep T. Nguyen, Carol B. Benson, Bryann Bromley, Jeffrey B. Campbell, Jeanne Chow, Beverly Coleman, Christopher Cooper, Jude Crino, Kassa Darge, C.D. Anthony Herndon, Anthony O. Odibo, Michael J.G. Somers, Deborah R. Stein; Multidisciplinary consensus on the classification of prenatal and postnatal urinary tract dilation (UTD classification system); Pediatric Urology; December 2014 Volume 10, Issue 6, Pages 982-998)
A liposomal formulation of the hydrochloride salt of the semisynthetic camptothecin analogue irinotecan with potential antineoplastic activity. During the S phase of the cell cycle, irinotecan selectively stabilizes topoisomerase I-DNA covalent complexes, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery. Liposome encapsulation of this agent promotes efficient drug delivery into the cytosol from the endosome compartment of the cell.
A third-generation, orally available, irreversible, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, osimertinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. AZD9291 preferentially inhibits mutated forms of EGFR including T790M, a secondarily-acquired resistance mutation, and may have enhanced anti-tumor effects in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.
A monoclonal antibody against the human dipeptidyl peptidase 4 (dipeptidylpeptidase IV, DPPIV, DPP4; CD26), with potential activity against graft-versus-host disease (GvHD). Upon administration, begelomab binds to CD26 expressed on T-cells. This inhibits the stimulation of T-cells and may prevent GvHD. CD26, a membrane-bound glycoprotein with dipeptidyl peptidase activity, plays a key role in T-cell activation and immune regulation.
Cardiac stroke volume index is the the volume of blood ejected per beat divided by body surface area, hence units of measurement are ml/m square - (cardiac) stroke volume index is therefore a more precise individual measurement.
A condition in which a child is chronically irritable and experiences frequent, severe temper outbursts that seem grossly out of proportion to the situation.
The reemergence of acute biphenotypic leukemia after a period of remission.
A molecular abnormality indicating rearrangement of the ALK gene.
A type of strabismus in which the visual axis of one eye is higher than that of the other. [ORCID:0000-0003-0986-4123]
Severe loss of visual acuity within hours or days. This is characteristic of Leber hereditary optic neuropathy. [HPO:probinson]
Chorioretinal atrophy along the retinal veins.
The presence of an abnormally large pelvis. [HPO:probinson]
A 'coloboma' (HP:0000589) of the ciliary body. []
An elevated circulating testosterone level in the blood. []
An anomaly of the circulating level of a gonadotropin, that is, of a protein hormone secreted by gonadotrope cells of the anterior pituitary of vertebrates. The primary gonadotropins are luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
An reduction of the circulating level of a gonadotropin, that is, of a protein hormone secreted by gonadotrope cells of the anterior pituitary of vertebrates. The primary gonadotropins are luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
An reduction of the circulating level of follicle-stimulating hormone (FSH).
A reduction in the circulating level of luteinizing hormone (LH).
An anomaly of the circulating level of follicle-stimulating hormone (FSH).
An anomaly in the blood concentration of an androgen, that is, of a steroid hormone that controls development and maintenance of masculine characteristics. The androgens include testosterone and Dehydroepiandrosterone.
An elevation of the blood concentration of an androgen, that is, of a steroid hormone that controls development and maintenance of masculine characteristics. The androgens include testosterone and Dehydroepiandrosterone.
A reduction in the blood concentration of an androgen, that is, of a steroid hormone that controls development and maintenance of masculine characteristics. The androgens include testosterone and Dehydroepiandrosterone.
A well-circumscribed, intensely pruritic, raised wheal (edema of the superficial skin) typically 1 to 2 cm in diameter.
An anomalous level of insulin-like growth factor 1 (IGF1) in the blood circulation.
A reduced level of insulin-like growth factor 1 (IGF1) in the blood circulation.
Abnormal levels of interferon in the blood.
Abnormal levels of interferon gamma measured in the blood circulation.
An elevation in the concentration of interferon gamma measured in the blood circulation.
An anomaly of the metabolism of an icosanoid (also know as eicosanoids). These are signaling molecules derived from oxidation of 20-carbon fatty acids. Most are produced from arachidonic acid, a 20-carbon polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid).
A reduction in the level of carnitine in muscle tissue.
Delivery by Caesarian section representing the first time the mother has delivered by Caesarian section.
Delivery by Caesarian section representing where the mother has already had a previous Cesarean delivery, and this is a repeat Cesarean birth.
Hyperphalangy is a digit morphology in which increased numbers of phalanges are arranged linearly within a digit. That is, there is an accessory phalanx that is arranged linearly with the other phalanges.
An accessory phalanx of the index (second) finger that is arranged linearly with the other phalanges. Hyperphalangy of the index finger results from an accessory ossification center at the metacarpophalangeal joint, resulting in radial deviation of the index finger. Note that this term refers only to this type of hyperphalangy.
Vaginal delivery following induction of labor, a procedure used to stimulate uterine contractions during pregnancy before labor begins on its own.
A deviation in the normal proportion of naive B cells (CD19+/CD27-/IgD+/IgM+) relative to the total number of B cells. Naive B cells represent one of the subtypes of B cells in the peripheral blood, and are B cells that have not been exposed to antigen.
An elevation above the normal proportion of naive B cells (CD19+/CD27-/IgD+/IgM+) relative to total number of B cells. Naive B cells represent one of the subtypes of B cells in the peripheral blood, and are B cells that have not been exposed to antigen.
A reduction below normal proportion of naive B cells (CD19+/CD27-/IgD+/IgM+) relative to total number of B cells. Naive B cells represent one of the subtypes of B cells in the peripheral blood, and are B cells that have not been exposed to antigen.
A deviation of the normal proportion of memory B cells (CD19+/CD27+) in circulation relative to total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV).
A reduction in the normal proportion of memory B cells (CD19+/CD27+) in circulation relative to the total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV).
An elevation in the proportion of memory B cells (CD19+/CD27+) in circulation relative to the total number of B cells. Memory B cells develop from naive B cells. Upon antigen rechallenge, memory B cells rapidly expand and differentiate into plasma cells under the cognate control of memory Th cells (Phase IV).
A deviation from normal proportion immature B cells (CD19+/ CD21low) in circulation relative to total number of B cells. Immature B cells (IgM+) are still in final stages of development within the bone marrow. Naive B cells are those which have left the bone marrow, before they bind to the antigen for which they're specific (IgM+/IgD+).
An elevation in the proportion above normal of immature B cells (CD19+/ CD21low) in circulation relative to total number of B cells. Immature B cells (IgM+) are still in final stages of development within the bone marrow. Naive B cells are those which have left the bone marrow, before they bind to the antigen for which they're specific (IgM+/IgD+).
A reduction in normal proportion of immature B cells (CD19+/ CD21low)in circulation relative to total number of B cells. Immature B cells (IgM+) are still in final stages of development within the bone marrow. Naive B cells are those which have left the bone marrow, before they bind to the antigen for which they're specific (IgM+/IgD+).
A deviation in the normal proportion of transitional B cells (CD19+/CD38high/IgMhigh) in circulation relative to the total number of B cells. B cells originate from precursors in the bone marrow, and the first cells which migrate to the peripheral blood have been classified as transitional B cells.
A reduction in the normal proportion of transitional B cells (CD19+/CD38high/IgMhigh) in circulation relative to the total number of B cells. B cells originate from precursors in the bone marrow, and the first cells which migrate to the peripheral blood have been classified as transitional B cells.
An elevation in the normal proportion of transitional B cells (CD19+/CD38high/IgMhigh) in circulation relative to the total number of B cells. B cells originate from precursors in the bone marrow, and the first cells which migrate to the peripheral blood have been classified as transitional B cells.
A deviation of the normal proportion of marginal zone B cells (CD19+/CD27+/IgM+/IgD+) in circulation relative to the total number of B cells.
A reduction in the normal proportion of marginal zone B cells (CD19+/CD27+/IgM+/IgD+) in circulation relative to the total number of B cells.
An elevation in the normal proportion fof marginal zone B cells (CD19+/CD27+/IgM+/IgD+) in circulation relative to the total number of B cells. [HPO:probinson, PMID:9802980]
A deviation of the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM-/IgD-) in circulation relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.
A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.
An anomaly of the metabolism of thromboxane (CHEBI:26995). Thromboxanes are derived from prostaglandin precursors in platelets, and stimulate aggregation of platelets and constriction of blood vessels.
An anomaly of the metabolism of leukotriene (CHEBI:25029).
Reduced ability of lexical discrimination, which refers to the process of distinguishing a stimulus word from other phonologically similar words. Lexical discrimination can be defined as the process of correctly identifying words in the mental lexicon to match the phonological input of a stimulus.
Platelets are replete with secretory granules, which are critical to normal platelet function. Among the three types of platelet secretory granules - alpha-granules, dense granules, and lysosomes - the alpha-granule is the most abundant. Granule contents must be released from their intracellular repository in order to achieve their physiologic function, and this term refers to a functional defect in granule secretion.
Abnormal release of dense granules from platelets.
Abnormal secretion of the platelet dense-granule content adenosine triphosphate (ATP).
Abnormal release of alpha granule contents from platelets.
Abnormal release of lysosome contents from platelets.
Deviation from normal of the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) within platelets.
A malignant epithelial tumor with a glandular organization that originates in the jejunum.
A malignant epithelial tumor with a glandular organization that originates in the ileum.
A low-grade variant of squamous cell carcinoma of the tongue with a warty (verrucous) appearance.
A cyst of the ovary that exhibits deposition of calcium salts.
A benign central bone tumor of the jaw composed of fibrous connective tissue within which bone is formed.
A melanoma that originates in the anal margin.
A tumor that arises from an element of the autonomic nervous system.
A type of mesenteric cyst that is lined with a thin endothelium or mesothelium and filled with chylous and lymphatic fluid.
No detectable response to the light-adapted 3.0 ERG (single-flash cone response). This type of ERG measures responses of the cone system; a-waves arise from cone photoreceptors and cone off-bipolar cells; the b-wave comes from On- and Off-cone bipolar cells.
An anomalous response to a pattern electroretinogram (PERG), a particular kind of ERG obtained in response to contrast modulation of patterned visual stimuli at constant mean luminance-typically contrast-reversing gratings or checkerboards-whose characteristics are fundamentally different from those of the traditional ERG in response to diffuse flashes of light.
An abnormal reduction in the amplitude of the a-wave.
An anomaly of the pigmentation in the fovea centralis.
Small, red dots in the superficial retinal layers (it is difficult to distinguish between small hemorrhages and microaneurysms).
Any structural anomaly of the blood vessels of the macula.
Fluffy white patch on the macula, representing localized areas of dense white swelling of the retinal nerve fibre layer. They often have a zigzag internal structure, a feathered edge but an otherwise well-delineated form and an approximately 1 mm dimension; they project slightly into the vitreous and sometimes deflect retinal vessels.
Abnormal increase in retinal thickness in the macular area observed on fundoscopy or fundus imaging.
Clumped pigmentary changes of nummular appearance (i.e., thought to resemble the shape of a coin or multiple coins stuck together) at the level of the retinal pigment epithelium.
A diminution of the peripheral visual field whereby at least 50 degrees of central field are preserved in all meridians.
Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Autofluorescent patterns result from the complex interaction of fluorophores such a lipofuscin, which release an autofluorescent signal, and elements such as melanin and rhodopsin, which absorb the excitation beam and attenuate autofluorescence. Other structures such as retinal vessels and the crystalline lens may also influence autofluorescence through blocking and interference.
An abnormality observed by retinal fluorescein angiography, which involves the intravenous injection of fluorescein dye followed by fluorescent imaging of the fundus immediately after injection and for up to ten minutes thereafter. It can be used to study various retinal abnormalities including especially anomalies of the choroidal and retinal circulation.
Loss of the outer nuclear layer (photoreceptor layer) as assessed by ocular coherence tomography.
Increased amount of autofluorescence in the macula as ascertained by fundus autofluorescence imaging.
Decreased amount of autofluorescence in the macula as ascertained by fundus autofluorescence imaging.
Vitreous haze is the obscuration of fundus details by vitreous cells and protein exudation.
Any cystic lesion associated with the umbilical cord.
Branching of the umbilical cord before its insertion into the placenta.
The presence of inflammatory cells such as lymphocytes and macrophages in the vitreous.
Vestigial vitreous gel occupying the immediate retrolental space and minimal to no discernable gel in the central vitreous cavity, giving the appearance of an empty vitreous cavity.
A cyst that is localized in the region of the orbit and exhibits an epithelial lining with a keratin-filled lumen. Hair follicles are one of the adnexal structures that are commonly found in walls of dermoid cysts.
An anomaly of the adjacent structures (i.e., adnexa) of the eye, defined as the lacrimal apparatus, the extraocular muscles and the eyelids, eyelashes, eyebrows and the conjunctiva.
A hamartoma (disordered proliferation of mature tissues) which can originate from any tissue of the orbital region.
Any anomaly of the ring of fibrous tissue that surrounds the optic nerve at its entrance at the apex of the orbit. The common tendinous ring, also know as the annulus of Zinn or annular tendon, is the origin for five of the seven extraocular muscles.
Chronic loss of joint motion of the proximal interphalangeal joint of the 2nd, 3rd, 4th, and 5th fingers due to structural changes in non-bony tissue.
A congenital auricular deformity, which is mainly characterized by a bulging appearance of the anterosuperior portion of the auricle, a convexly protruded cavum conchae, and a slit-like narrowing of the orifice of the external auditory meatus.
A hypopigmented spot in the shape of a leaf from the mountain ash tree.
A deviation from the normal circulating concentration of adiponectin, a 30-kDa complement C1-related protein that is the most abundant secreted protein expressed in adipose tissue, and that plays a crucial role in the regulation of insulin sensitivity and glucose metabolism.
A reduced circulating concentration of adiponectin, a 30-kDa complement C1-related protein that is the most abundant secreted protein expressed in adipose tissue.
An elevated circulating concentration of adiponectin, a 30-kDa complement C1-related protein that is the most abundant secreted protein expressed in adipose tissue.
A deviation from the normal concentration of glucagon in the blood circulation.
The inability to maintain postures or positions (such as keeping eyes closed, protruding the tongue, maintaining conjugate gaze steadily in a fixed direction, or making a prolonged 'ah' sound) without repeated prompts.
A subset of motor impersistence, defined as the inability to perform more than two of the simple voluntary acts simultaneously, such as closing the eyes and protruding the tongue.
Abnormal concentration of neopterin in the cerebrospinal fluid (CSF).
Increased concentration of neopterin in the cerebrospinal fluid (CSF).
Decreased concentration of dopamine in the cerebrospinal fluid (CSF). []
The presence of an abnormal concentration of neopterin.
Abnormal concentration of biopterin in the cerebrospinal fluid (CSF).
Increased concentration of biopterin in the cerebrospinal fluid (CSF).
Decreased concentration of biopterin in the cerebrospinal fluid (CSF).
The presence of an abnormal concentration of biopterin.
An abnormality of the skin of the palm, that is, the skin of the front of the hand.
An abnormal concentration of insulin in the body.
An abnormal concentration of insulin in the blood.
An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements. [HPO:probinson, PMID:20042774]
Lack of natural killer cells, a type of lymphocyte in the innate immune system that contains cytoplasmic granzymes, i.e., small granules with perforin and proteases that allow natural killer cells to form pores in the cell membrane of the target cell through which the granzymes and associated molecules can enter, inducing apoptosis.
A reduced level of the complement component C4 in the circulation.
A reduced level of the complement component C4a in circulation.
An elevated concentration in the blood of hemoglobin A2 (HbA2), which is a normal variant of hemoglobin A that consists of two alpha and two delta chains and is normally present at low levels in adults but may be increased in beta thalassemia.
An abnormal amount of oxygen passes into the blood from the lungs and/or an abnormal amount of carbon dioxide passes from the blood into the lungs.
Any abnormality of the brachial nerve plexus.
Any abnormality of the lumbosacral nerve plexus.
A diagnostic alternating light and dark banding pattern under polarizing microscopy.
An anomaly of the size of the testicle (the male gonad).
Increased density of hairs, i.e., and elevated number of hairs per unit area.
Abnormality of the first branch of the internal carotid artery.
Any abnormality of the part of the nervous system that consists of the nerves and ganglia outside of the brain and spinal cord.
Any abnormality of the part of the peripheral nervous system associated with sensation and skeletal muscle voluntary control of body movements.
Any abnormality of the somatic nerve plexus.
Any abnormality of the masticatory muscle.
Any abnormality of the submandibular region, the region between the mandible and the hyoid bone contains the submandibular and sublingual glands, suprahyoid muscles, submandibular ganglion, and lingual artery.
An abnormality of nerve cell cluster or a group of nerve cell bodies located in the autonomic nervous system.
An abnormality of nerve cell cluster or a group of nerve cell bodies located in the peripheral autonomic nervous system.
An abnormality of nerve cell cluster or a group of nerve cell bodies located in the autonomic nervous system of the cranium.
An abnormality of one or more of the five muscles of the soft palate.
An abnormality of any of the muscles of the pharynx.
An abnormality of the tensor veli palatini muscle
An abnormality of the muscles of the structure of the nose.
An abnormality of any of the muscles of facial expression, which are innervated by the seventh (VII) cranial nerve and control facial expression.
An abnormality of the levator labii superioris alaeque nasi muscle.
An abnormality of the common carotid arteries, which provide the arterial supply to the head and neck and give rise to the internal carotid artery and the external carotid artery.
An abnormality of the sphenoid sinus, one of the mucosa-lined, normally air-filled paranasal sinuses of the bones of the skull. The sphenoid sinus is located within the sphenoid bone.
An abnormality of the maxillary sinus, one of the mucosa-lined, normally air-filled paranasal sinuses of the bones of the skull. The maxillary sinus is located within the skeleton of the midface, lateral to the nasal cavity.
An abnormality of an external jugular vein of the neck.
Two-sided or bilateral weakness of the muscles of facial expression and eye closure.
An abnormal morphology (form) of the midface or its components, the cheeks, maxilla, zygomatic bone, malar region, and infraorbital rims.
An abnormality of the premaxilla (the embryonic structure that forms the anterior part of the maxilla) causing it to appear relatively large in size compared to the other parts of the maxilla or other facial structures.
Any structural anomaly of an inner ear epithelium.
An abnormality of a frontalis muscle belly.
An abnormality of a medial pterygoid muscle.
An abnormality of an orbicularis oris muscle.
An abnormality of a palatoglossus muscle.
An abnormality of a palatopharyngeus muscle.
An abnormality of the styloglossus muscle.
An abnormality of a zygomaticus major muscle.
An abnormality of a zygomaticus minor muscle.
An abnormality of a cartilage of external ear.
An abnormality of the angular artery, the terminal branch of the facial artery.
Any structural abnormality of a facial artery, one of the branches of the external carotid artery.
An abnormality of a depressor anguli oris muscle.
An abnormality of a depressor labii inferioris.
An abnormality of a central retinal artery.
Any abnormality of nasopharyngeal adenoids.
An abnormality of a cartilage of nasal septum.
Abnormality of the plexus of the ventral rami of the first four cervical spinal nerves which are located from C1 to C4 cervical segment in the neck.
An abnormality of a blood vessel of the head, including branches of the arterial and venous systems of the head.
An abnormality of a blood vessel of the neck, including branches of the arterial and venous systems of the neck.
Any structural abnormality of a cricoid cartilage, that is, of the ring-shaped cartilage of the larynx.
An abnormality of a dorsal nasal artery.
An abnormality of an external carotid artery.
Any structural abnormality of a jugular vein.
An abnormality of a frontal process of the maxilla bone.
An abnormality of a genioglossus muscle.
Any structural anomaly of the glossopharyngeal nerve, the ninth paired cranial nerve (CN IX).
Any structural anomaly of a great auricular nerve.
An abnormality of a greater palatine artery.
An abnormality of an inferior alveolar artery.
An abnormality of an inferior alveolar nerve.
An abnormality of an artery of lower lip.
An abnormality of an inferior oblique extraocular muscle.
An abnormality of an inferior rectus extraocular muscle.
An abnormality of an inferior thyroid vein.
An abnormality of an infraorbital artery.
A structural abnormality of an infra-orbital nerve. The infraorbital nerve arises from the maxillary branch of the trigeminal nerve and normally traverses the orbital floor in the infraorbital canal.
An abnormality of an internal jugular vein.
An abnormality of an intrinsic muscle of tongue.
Any structural abnormality of a lateral crico-arytenoid muscle, which extends from the lateral cricoid cartilage to the muscular process of the arytenoid cartilage, and can adduct the vocal cords, which closes the rima glottidis and thereby protects the airway.
An abnormality of a lateral pterygoid muscle.
An abnormality of a lateral rectus extra-ocular muscle.
An abnormality of a levator anguli oris.
An abnormality of a levator labii superioris.
An abnormality of a levator palpebrae superioris.
An abnormality of a levator veli palatini.
Any structural abnormality of a lingual artery.
Any structural anomaly of a lingual nerve.
An abnormality of a mandible condylar process.
An abnormality of a mandible coronoid process.
A structural abnormality of a mandibular symphysis.
An abnormality of an anterior ethmoidal artery.
An increase in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.
Any structural anomaly of the muscular columns which project from the inner surface of the right and left ventricles of the heart (cardiac trabeculae, trabeculae carneae).
Complete inability to conceive or induce conception.
Potential for inadequate physiological activity of the urinary system to excrete fluids and waste and maintain blood pressure and fluid and electrolyte balance.
Potential for physical harm, damage to skin and soft tissue, eyes, reproductive system and circulatory system and loss of hair sustained from ionizing radiation.
Gingivitis involving less than 30% of the gingiva.
Inflammation characterised by gingival redness and swelling with bleeding on probing (provocation).
Potential for inadequate physiological activity of the gastrointestinal tract and organs causing discomfort or interference with the breaking down of food for absorption and elimination of wastes.
Sexual activity has occurred in the six months prior to the current time.
Sexual activity has occurred in the month prior to the current time.
Sexual activity has occurred in the year prior to the current time.
Gingivitis involving the entire mouth or more than 30 percent of the surfaces.
Failure of neuromuscular block reversal agents to antagonise a neuro muscular blocking drug.
Chronic hepatitis B with negative hepatitis B surface antigen and low level viral replication but positive hepatitis B virus deoxyribonucleic acid test.
Local contributing factors include improperly contoured restorations, missing or worn restorations, or gingival architecture that is unusual and allows for accumulation of food debris.
A form of sexual abuse where the child is sexually exploited for money, power or status.
A new narcotic or psychotropic drug that is not controlled by the United Nations drug conventions, but which may pose a public health threat comparable to that posed by substances listed in these conventions.
History of high blood pressure and protein in urine during pregnancy.
Inability to evacuate bowels properly, characterized by difficulty passing motions and a sensation of blockage or incomplete emptying.
Decalcification of bone or abnormal bone development due to chronic KIDNEY DISEASES, in which 1,25-DIHYDROXYVITAMIN D3 synthesis by the kidneys is impaired, leading to reduced negative feedback on PARATHYROID HORMONE. The resulting SECONDARY HYPERPARATHYROIDISM eventually leads to bone disorders.
Person has been witness to an adult misusing substances.
Person has been witness to an adult misusing alcohol.
A systolic blood pressure >=150 mm Hg or diastolic blood pressure >=90 mm Hg while lying down.
Clusters of enlarged lymph nodes which are small, often hard and usually of no clinical concern. They have a similar feel to buckshot or pellets.
A radiotracer composed of a truncated form of the azo dye Evans blue (EB) conjugated, via a 1,4,7-triazacyclononane-N,N',N""-triacetic acid (NOTA) linker (NEB), to the radioisotope gallium Ga 68, with potential blood pool imaging activity for use in positron emission tomography (PET). Upon administration of gallium Ga 68-NEB, the NEB moiety, which has high affinity for serum albumin, targets and forms a complex with albumin. Upon PET, the lymph nodes (LN) and lymphatic vessels as well as other desired tissues can be visualized.
An orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, acalabrutinib inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against B-cell antigen receptor complex-associated protein beta chain (CD79B) conjugated, via a protease-cleavable peptide linker, to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule inhibitor, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of polatuzumab vedotin selectively binds to CD79B, a protein which is abundantly expressed on the surface of B-cells. Upon internalization and proteolytic cleavage, MMAE binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. CD79B, a component of the B-cell receptor (BCR), plays a key role in B-cell receptor signaling and is expressed on the surface of almost all types of malignant B-cells.
A humanized monoclonal antibody directed against the tyrosine kinase receptor colony stimulating factor 1 receptor (CSF1R; CSF-1R; CD115), also known as macrophage colony-stimulating factor receptor (M-CSFR), with potential antineoplastic and immunomodulating activities. Upon administration, emactuzumab binds to CSF1R expressed on macrophages and inhibits the binding of colony-stimulating factor-1 (CSF-1) to CSF1R. This prevents CSF1R activation and CSF1R-mediated signaling in these cells, which blocks the production of inflammatory mediators by macrophages and reduces inflammation. By blocking both the activity of CSF1R-dependent tumor-associated macrophages (TAMs) and the recruitment of TAMs to the tumor microenvironment, emactuzumab enhances T-cell infiltration and antitumor T-cell immune responses, which inhibits the proliferation of tumor cells. TAMs play key roles in immune suppression and promoting inflammation, tumor cell proliferation and survival.
An orally available Raf kinase inhibitor with potential antineoplastic activity. Encorafenib specifically inhibits Raf kinase, a serine/threonine enzyme in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) signaling pathway. By inhibiting the activation of the RAF/MEK/ERK signaling pathway, the administration of LGX818 may result in a decrease in proliferation of tumor cells. The Raf mutation BRAF V600E is frequently upregulated in a variety of human tumors and results in the constitutive activation of the RAF/MEK/ERK signaling pathway that regulates cellular proliferation and survival.
An orally bioavailable small-molecule inhibitor of p38 and Tie2 kinases with potential antineoplastic, anti-inflammatory and antiangiogenic activities. Pexmetinib binds to and inhibits the activities of p38 and Tie2 kinases, which may inhibit the production of proinflammatory cytokines and may decrease tumor angiogenesis and tumor cell growth and survival. p38 is a MAP kinase that is often upregulated in cancer cells, playing a crucial part in the production of a variety of cytokines involved in inflammation and cellular proliferation such as tumor necrosis factor (TNF) and interleukin (IL)-1 and -6. Tie2 is an endothelial cell specific receptor that is activated by angiopoietins, growth factors required for angiogenesis. This agent has also been reported to inhibit other kinases including vascular endothelial growth factor receptor (VEGFR2) and Src tyrosine kinases.
An orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia.
An orally bioavailable, highly selective and potent small molecule inhibitor of the delta and gamma isoforms of phosphoinositide-3 kinase (PI3K) with potential immunomodulating and antineoplastic activities. Upon administration, duvelisib prevents the activation of the PI3K delta/gamma-mediated signaling pathways which may lead to a reduction in cellular proliferation in PI3K delta/gamma-expressing tumor cells. Unlike other isoforms of PI3K, the delta and gamma isoforms are overexpressed primarily in hematologic malignancies and inflammatory and autoimmune diseases. By selectively targeting these PI3K isoforms, PI3K signaling in normal, non-neoplastic cells is minimally or not affected which would result in a more favorable side effect profile.
An orally available, ATP-competitive inhibitor of the receptor tyrosine kinases, anaplastic lymphoma kinase (ALK) and C-ros oncogene 1 (Ros1), with potential antineoplastic activity. Upon administration, lorlatinib binds to and inhibits both ALK and ROS1 kinases. The kinase inhibition leads to disruption of ALK- and ROS1-mediated signaling and eventually inhibits tumor cell growth in ALK- and ROS1-overexpressing tumor cells. In addition, PF-06463922 is able to cross the blood brain barrier. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. ROS1, overexpressed in certain cancer cells, plays a key role in cell growth and survival of cancer cells.
A hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard (Br-IPM) conjugated with 2-nitroimidazole, with potential antineoplastic activity. When exposed to hypoxic conditions, such as those found in hypoxic tumors, the 2-nitroimidazole moiety of evofosfamide is reduced. This releases the DNA-alkylating Br-IPM moiety, which introduces intra- and inter-strand DNA crosslinks in nearby cells; the crosslinks inhibit both DNA replication and cell division, and may lead to apoptosis of cells in the tumor. The inactive form of the prodrug is stable under normoxic conditions, which may limit systemic toxicity.
A condition in which the anterior part of the foot rotates outward away from the midline of the body and the heel remains straight. [HPO:curators]
Oxytocin (9 aa, ~1 kDa) is encoded by the human OXT gene. This protein plays a role in smooth muscle contraction in both the mammary gland and uterus. Oxytocin also may also be involved in maternal-newborn bonding, cognition and many other psychological and physiological processes.
An auto inflammatory syndrome with characteristics of recurrent febrile episodes associated with aphthous stomatitis, pharyngitis and cervical adenitis. Usually presents during early childhood with recurrent episodes of fever during which children appear very ill. Aphthous stomatitis presents with relatively painless small, round and shallow lesions on the tongue and oral mucosa that recover completely in 10-14 days. Most patients present with tonsillitis, occasionally with white exudates and a general pharyngitis. Episodes recur every 3-5 weeks, often in a predictable fashion with patients describing a mild malaise the day before recurrence. An idiopathic inflammatory condition.
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the thumb. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones. [HPO:probinson]
A foot anomaly in which the forefoot (METATARSUS) is angled inward relative to the heel.
Carbamoyl phosphate synthetase I deficiency is an autosomal recessive inborn error of metabolism of the urea cycle which causes hyperammonemia. There are 2 main forms: a lethal neonatal type and a less severe, delayed-onset type (summary by Klaus et al., 2009). Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: ornithine transcarbamylase deficiency (311250), carbamyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, or citrullinemia (215700), argininosuccinate lyase deficiency (207900), and arginase deficiency (207800).
A cavity within the cerebral hemisphere, filled with cerebrospinal fluid, that communicates directly with the ventricular system. [HPO:probinson, PMID:9279052]
A cavity within the cerebral hemisphere, filled with cerebrospinal fluid, that communicates directly with the ventricular system.
A benign fluid filled simple cyst of bone filled with serous fluid. [HPO:probinson]
Charcot-Marie-Tooth disease type 4 (CMT4) belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathy diseases. Type 4 is less common and often limited to certain ethnic groups. Patients present with the typical CMT phenotype along with typical features of progressive, distally accentuated weakness and atrophy of muscles innervated by the peroneal nerve in the lower limbs, followed by weakness and atrophy of hands, sensory loss, and characteristic foot abnormalities.
A transient reduction in the number of erythroblasts in the circulation.
The carboxylic acid formed by the oxidation of the first carbon of glucose with antiseptic and chelating properties. Gluconic acid, found abundantly in plant, honey and wine, can be prepared by fungal fermentation process commercially. This agent and its derivatives can used in formulation of pharmaceuticals, cosmetics and food products as additive or buffer salts. Aqueous gluconic acid solution contains cyclic ester glucono delta lactone structure, which chelates metal ions and forms very stable complexes. In alkaline solution, this agent exhibits strong chelating activities towards anions, i.e. calcium, iron, aluminium, copper, and other heavy metals.
Bulbar weakness (or bulbar palsy) refers to bilateral impairment of function of the lower cranial nerves IX, X, XI and XII, which occurs due to lower motor neuron lesion either at nuclear or fascicular level in the medulla or from bilateral lesions of the lower cranial nerves outside the brain-stem. Bulbar weakness is often associated with difficulty in chewing, weakness of the facial muscles, dysarthria, palatal weakness and regurgitation of fluids, dysphagia, and dysphonia. [HPO:curators]
A developmental anomaly characterized by a reduced number of teeth, whereby more than 6 teeth are missing.
An immunoglobulin blood product given to the pregnant mother that helps to prevent the Rh negative mother from developing an antibody response to the Rh positive blood cells of the fetus.
Follitropin subunit beta (129 aa, ~15 kDa) is encoded by the human FSHB gene. This protein plays a role in induction of egg and sperm production.
A murine monoclonal antibody directed against the CD20 phosphoprotein, expressed on the cell surface of normal B-lymphocytes and B-cell lymphomas.
Any abnormality of bones of the arms or legs.
invasion and growth of microorganisms in the gastrointestinal system; may be clinically inapparent or result in local cellular injury.
Degenerative brain disease linked to repetitive brain trauma. Progressive symptoms may include MEMORY LOSS; AGGRESSION; or DEPRESSION.
A syndrome of mental retardation/multiple congenital malformations that is caused by the total or partial duplication of the short arm of chromosome 10. Around 50 cases have been described in the literature. The anomalies are present at birth. Children are usually dolichocephalic with a high and prominent forehead, contrasting with a small face. Osteoarticular anomalies are frequent, including ligament hyperlaxity, flexion deformations of limbs, and club feet. Cardiac, renal, ocular and bone malformations have been reported. The majority of cases are a result of the malsegregation of a familial balanced translocation. The most frequent break point is located at the level of p11 band, but it can be more distal and result in partial trisomy.
Deletion of a part of the short arm of chromosome X (Xp22) associated with short stature, chondrodysplasia punctata, ichthyosis, mental deficiency, and elements of Kallmann syndrome (a disorder of hypothalamic function and reduced pituitary gonadotropic activity with resulting hypogonadism and agenesis or hypoplasia of the olfactory bulb with olfactory disorders).
An electrocardiographic finding of an ectopic impulse originating in the atria and not specifically in the sinus node. The P wave morphology of these complexes is often different from a sinus P wave and the RR intervals preceding these complexes is also shorter than those of the regular beats. (CDISC)
A small hardy fan palm, endemic to coastal plains from South Carolina to southeastern Louisiana including the Florida peninsula, whose stem usually remains below ground or runs just along the surface. In some cases, it develops an erect or arching trunk that may lift the whorl of leaves 2-8 ft (0.6-2.4 m) above ground. The palmate leaves are 2-3 ft (0.6-0.9 m) across and green or bluish green. The cluster of leaves gets about 4-6 ft (1.2-1.8 m) high with a similar spread. In the wild, saw palmetto often grows in clumps 20 ft (6 m) or more in diameter. Drugs extracted from its berries have been used to treat, prostrate swelling, bladder infections and urinary tract infections.
A hybrid between A. pavia and A. hippocastanum.
Formation of a blood clot (thrombus) in the lumen of a mesenteric vein or mesenteric artery.
A fulminating disease of neonates in which there is extensive mucosal ulceration, pseudomembrane formation, submucosal hemorrhage, and necrosis usually of the right colon, cecum, terminal ileum, and appendix, possibly due to perinatal intestinal ischemia and bacterial invasion. Progression can lead to necrosis, perforation and/or scarring of the intestinal tract.
Progressive spinal muscular atrophy, i.e., muscular weakness and atrophy related to loss of the motor neurons of the spinal cord and brainstem. [HPO:curators]
Underdevelopment or reduced size of the heart right ventricle, often due to a reduced number of cells.
A term referring to the lack of definitive criteria for classification of a finding.
Guillain-Barre syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy characterized most commonly by symmetric limb weakness and loss of tendon reflexes. It is a putative autoimmune disorder presenting after an infectious illness, most commonly Campylobacter jejuni, a gram-negative bacterium that causes acute enteritis (Yuki and Tsujino, 1995; Koga et al., 2005). Approximately 1 in 1,000 individuals develops GBS after C. jejuni infection (Nachamkin, 2001). Although rare familial cases have been reported, GBS is considered to be a complex multifactorial disorder with both genetic and environmental factors rather than a disorder following simple mendelian inheritance (Geleijns et al., 2004).
Individuals with multiple self-healing squamous epithelioma (MSSE) develop multiple invasive skin tumors that undergo spontaneous regression leaving pitted scars. Age at onset is highly variable, ranging from 8 to 62 years. The disorder shows autosomal dominant inheritance, and most affected families have originated from western Scotland (Bose et al., 2006). MSSE has been considered to be a variety of multiple keratoacanthoma (Biskind et al., 1957; Haydey et al., 1980).
An electrocardiographic finding of an acute myocardial infarction which produces characteristic elevations of the ST segment of the ECG.
A chimeric recombinant IgG1 monoclonal antibody directed against human CD20 with potential antineoplastic activity. Ublituximab specifically binds to the B cell-specific cell surface antigen CD20, thereby potentially inducing a B cell-directed complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) against CD20-expressing B cells, leading to B cell apoptosis. CD20 is a non-glycosylated cell surface phosphoprotein that is exclusively expressed on B cells during most stages of B cell development and is often overexpressed in B-cell malignancies. Ublituximab has a specific glycosylation profile, with a low fucose content, that may enhance its ADCC response against malignant B cells.
A sausage shape with cracks in the surface; normal stool.
Reactive astrocytic proliferation often associated with degenerative, inflammatory or neoplastic changes in the central nervous system.
A subjective response indicating that something improved.
A preparation of genetically modified autologous T-lymphocytes transduced with a retroviral vector expressing a chimeric antigen receptor (CAR) targeting the human tumor-associated antigen (TAA) MUC16ecto and encoding the human pro-inflammatory cytokine interleukin-12 (IL-12), fused to the signaling domain of the zeta chain of the TCR/CD3 complex (28z), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, 4H11-28z/fIL-12/EGFRt-expressing autologous T-lymphocytes are directed to and induce selective toxicity in MUC16-expressing tumor cells. In addition, the T-cells secrete IL-12 which induces secretion of interferon-gamma, promotes the activation of natural killer cells (NKs), and induces cytotoxic T-cell responses against tumor cells, which may result in immune-mediated tumor cell death and inhibition of tumor cell proliferation. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) response. MUC16, a transmembrane protein and glycosylated mucin, is overexpressed on the cell surface of the majority of ovarian cancer cells but not on healthy cells. MUC16ecto is the extracellular portion of MUC-16 and is the part that is retained by cells after cleavage of CA-125.
A blood concentration of prostate specific antigen below 5 ng/mL.
Charcot-Marie-Tooth disease type 2U (CMT2U) is an autosomal dominant neurologic disorder characterized by late-adult onset of distal sensory impairment resulting in distal muscle weakness and atrophy affecting the upper and lower limbs. The disorder is slowly progressive (summary by Gonzalez et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
A radiologic finding that describes haziness around a bronchus or large bronchiole seen end on. It may either represent bronchial wall thickening or fluid around the bronchi.
The abnormal formation of bone or bony substance.
A response indicating that an individual expects to, or is expected to, live less than twenty years.
A natural or synthetically-derived peptide that selectively kills or inhibits the growth of microorganisms; it may also have immunomodulatory activity.
A type of exocardia in which the heart develops outside of the body.
A solution containing a high concentration of cromolyn sodium, with potential mast cell stabilizing, anti-tussive and anti-inflammatory activities. Upon inhalation of PA101 via a nebulizer, cromolyn blocks calcium ion influx into mast cells, thereby preventing the degranulation of mast cells in the lungs. This blocks the release of pro-inflammatory mediators from mast cells, such as histamine and slow-reacting substance of anaphylaxis (SRS-A), and prevents both bronchoconstriction and an inflammatory response. In indolent systemic mastocytosis (ISM), PA101 may be able to reduce the symptoms associated with this disease
A non-specified abnormality; an abnormality that is not included in a specified grouping of abnormalities.
Myoclonic-atonic epilepsy is an autosomal dominant disorder characterized by onset of absence and myoclonic seizures in early childhood. Patients have delayed development before the onset of seizures and show varying degrees of intellectual disability following seizure onset (summary by Carvill et al., 2015).
Male EBP disorder with neurologic defects is an X-linked recessive disorder representing a continuous phenotypic spectrum with variable manifestations associated with a defect in sterol biosynthesis. Features include intellectual disability, short stature, scoliosis, digital abnormalities, cataracts, and dermatologic abnormalities. Not all patients show all features, and the severity is highly variable. Molecular studies indicate that affected males are hemizygous for a nonmosaic hypomorphic EBP allele. Carrier females are generally clinically asymptomatic, but may show biochemical abnormalities (summary by Arnold et al., 2012 and Barboza-Cerda et al., 2014).
Osteofibrous dysplasia is a tumor-like bone lesion that usually presents as a painless swelling or anterior bowing of the tibia (Park et al., 1993), although pain may occur in up to 25% of cases and presentation may follow pathologic fracture. Most reports of osteofibrous dysplasia describe isolated tibial lesions, although a significant subgroup describe isolated and ipsilateral fibular involvement. Cases with ulnar and radial involvement have been reported (summary by Hunter and Jarvis, 2002). OSFD is characterized by radiolucent lesions located at the periosteal surface of the diaphyseal cortex, almost exclusively of the tibia and fibula. These lesions are congenital and spontaneously resolve during skeletal maturation; the residuum is most commonly mild bowing at the affected site. Prior to their resolution, secondary complications such as nonunion fractures and pseudoarthrosis formation can occur. Histologically, OSFD lesions exhibit 'zonal architecture' characterized by spindle-shaped fibroblast-like cells in the center of the lesions that are progressively replaced with peripherally located, more differentiated cells from the osteoblastic lineage. The cells lying at the center of the lesions stain for markers of undifferentiated mesenchymal cell states, whereas bridging zones of osteoid with surface osteoblasts and embedded osteocytic cells are interspersed between the lesions. In OSFD, the unossified zones eventually mineralize after replacement with normal osteoid and, finally, bone. This histologic progression corresponds with the clinical and radiographic resolution of the lesions (summary by Gray et al., 2015). Hunter and Jarvis (2002) noted that there may be a relationship between osteofibrous dysplasia and adamantinoma of long bones (102660), although the latter condition usually presents at a later age.
Optic atrophy-8 (OPA8) is an autosomal dominant neurologic disorder characterized by progressive visual loss during the first or second decade of life. Some patients may have additional features, mainly late-onset sensorineural hearing loss. For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
Paget disease of bone-6 is an autosomal dominant disorder characterized by adult onset of bone pain associated with polyostotic bone lesions primarily affecting the axial skeleton. A subset of patients can develop coronary artery disease and/or malignant giant cell tumor (GCT) of the bone, which arises within the Paget bone lesions (summary by Divisato et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of Paget disease of bone, see 167250.
Paget disease is a metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone resorption and disorganized bone structure. See reviews by Ralston et al. (2008) and Ralston and Albagha (2014). For a discussion of genetic heterogeneity of Paget disease of bone, see 167250.
Paget disease is a metabolic bone disease characterized by focal abnormalities of increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Bone lesions in this disorder show evidence of increased osteoclastic bone resorption and disorganized bone structure. See reviews by Ralston et al. (2008) and Ralston and Albagha (2014). Genetic Heterogeneity of Paget Disease of Bone Also see PDB2 (602080), caused by mutation in the TNFRSF11A gene (603499) on chromosome 18q21; PDB4 (606263), mapped to chromosome 5q31; PDB5 (239000), caused by mutation in the TNFRSF11B gene (602643) on chromosome 8q24; and PDB6 (616833), caused by mutation in the ZNF687 gene (610568) on chromosome 1q21. Suggestive linkage of a form of PDB to chromosome 6p (PDB1) was reported by Fotino et al. (1977); however, further studies did not confirm linkage to this site (Moore and Hoffman, 1988; Nance et al., 2000; Good et al., 2001).
A finding that indicates an anatomic structure is partially or completely turned inside out.
Dendritic epidermal T cells express an invariant V-gamma-5/V-delta-1 T-cell receptor and account for 95% of all resident T cells in mouse epidermis. Skint1, which is expressed specifically in keratinocytes and thymic epithelial cells, is critical for development of dendritic epidermal T cells in mice. In contrast to the functional Skint1 gene in rodents, humans and all hominoid primates have an inactivated SKINTL pseudogene and lack authentic dendritic epidermal T cells (summary by Mohamed et al., 2015).
A congenital anatomic defect characterised by a facial cleft that extends from the mouth to the orbit of the eye.
A long-acting formulation composed of 7-ethyl-10-hydroxycamptothecin (SN38), a camptothecin derivative and active metabolite of irinotecan conjugated to polyethylene glycol (PEG), via a proprietary, cleavable linker, with potential antineoplastic activity. Upon administration, the proprietary linkage system allows for very slow release of SN38 from the formulation. Upon release, SN38 selectively stabilizes covalent topoisomerase I-DNA complexes, and results in single-stranded and double-stranded DNA breaks, the inhibition of DNA replication, and the induction of apoptosis. This agent is designed to deliver the active metabolite to tumor cells without the need for conversion as is the case with irinotecan. Compared to other PEG-SN38-based formulations, the linker system in DFP-13318 increases its half-life and the exposure time for tumor cells, while decreasing both blood plasma concentrations and exposure to off-target organs; this results in increased efficacy.
An inherited condition caused by mutation(s) in the DDX3X gene, encoding ATP-dependent RNA helicase DDX3X. It is characterized by severe intellectual disability and variable neurologic features.
CHOPS syndrome is a disorder involving multiple abnormalities that are present from birth (congenital). The name ""CHOPS"" is an abbreviation for a list of features of the disorder including cognitive impairment, coarse facial features, heart defects, obesity, lung (pulmonary) involvement, short stature, and skeletal abnormalities.Children with CHOPS syndrome have intellectual disability and delayed development of skills such as sitting and walking. Characteristic facial features include a round face; thick hair; thick eyebrows that grow together in the middle (synophrys); wide-set, bulging eyes with long eyelashes; a short nose; and down-turned corners of the mouth.Most affected individuals are born with a heart defect called patent ductus arteriosus (PDA). The ductus arteriosus is a connection between two major arteries, the aorta and the pulmonary artery. This connection is open during fetal development and normally closes shortly after birth. However, the ductus arteriosus remains open, or patent, in babies with PDA. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly; in severe cases, it can lead to heart failure. Multiple heart abnormalities have sometimes been found in children with CHOPS syndrome. In addition to PDA, affected individuals may have ventricular septal defect, which is a defect in the muscular wall (septum) that separates the right and left sides of the heart's lower chamber.People with CHOPS syndrome have abnormalities of the throat and airways that cause momentary cessation of breathing while asleep (obstructive sleep apnea). These abnormalities can also cause affected individuals to breathe food or fluids into the lungs accidentally, which can lead to a potentially life-threatening bacterial lung infection (aspiration pneumonia) and chronic lung disease. Affected individuals are shorter than more than 97 percent of their peers and are overweight for their height. They also have skeletal differences including unusually short fingers and toes (brachydactyly) and abnormally-shaped spinal bones (vertebrae).Other features that can occur in CHOPS syndrome include a small head size (microcephaly); hearing loss; clouding of the lens of the eye (cataract); a single, horseshoe-shaped kidney; and, in affected males, undescended testes (cryptorchidism).
Loss of all or part of the products of conception prior to the scheduled c-section date or expected delivery date.
A congenital heart malformation characterised by incomplete separation of the truncus arteriosus and the aorticopulmonary trunk, resulting in communication between the aorta and pulmonary trunk.
Separate hard lumps, hard to pass; indicative of severe constipation.
Lumpy and sausage-like; indicative of constipation.
Like a smooth, soft sausage or snake; normal stool.
Soft blobs with clear-cut edges, passed easily.
An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody against a tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of SC-003 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action.
Luscan-Lumish syndrome is characterized by macrocephaly, intellectual disability, speech delay, low sociability, and behavioral problems. More variable features include postnatal overgrowth, obesity, advanced carpal ossification, developmental delay, and seizures (Luscan et al., 2014; Lumish et al., 2015)
Atherosclerotic Cardiovascular Disease 10-Year Risk Estimator (ASCVD 10-Year Risk Estimator) Risk score.
ASSIGN Cardiovascular Disease 10-Year Risk Score (ASSIGN Score) Risk score.
An orally bioavailable ataxia telangiectasia mutated (ATM) kinase inhibitor, with potential chemo-/radio-sensitizing and antineoplastic activities. Upon oral administration, AZD0156 targets and binds to ATM, thereby inhibiting the kinase activity of ATM and ATM-mediated signaling. This prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. In addition, AZD0156 sensitizes tumor cells to chemo- and radiotherapy. ATM, a serine/threonine protein kinase, is upregulated in a variety of cancer cell types; it is activated in response to DNA damage and plays a key role in DNA-strand repair.
An aberrant or malpositioned long, narrow slit or groove that divides a tissue into distinct areas.
A flexure that is deviating from the norm or outwith the bounds of what is considered normal.
The formation of a lobe of tissue that is aberrant in comparison to normal anatomy.
An origin that is deviating from the norm or outwith the bounds of what is considered normal.
Any line of sutures that deviates from its normal anatomical location.
The lack of a long, narrow slit or groove that divides a tissue into distinct areas.
A replication-competent oncolytic adenovirus encoding the murine pro-inflammatory cytokine interleukin-12 (IL-12) gene and two suicide fusion genes, a yeast cytosine deaminase (yCD) and a mutant form of herpes simplex virus type 1 thymidine kinase (HSV-1 TKSR39), with potential immunomodulating and antineoplastic activities. Upon intratumoral administration of Ad5-yCD/mutTKSR39rep-hIL12, the adenovirus selectively infects and replicates in tumor cells, which results in direct tumor cell lysis. Synergistically, IL-12 expressed by the adenovirus may activate the immune system by promoting the activation of natural killer cells (NKs), inducing secretion of interferon-gamma (IFN-g) and inducing cytotoxic T-lymphocyte (CTL) responses against tumor cells, which may result in immune-mediated tumor cell death, inhibition of tumor cell proliferation and inhibition of tumor angiogenesis. In addition, Ad5-yCD/mutTKSR39rep-hIL12-infected cancer cells express yCD and TKSR39; upon administration of the prodrugs 5-fluorocytosine (5-FC) and valganciclovir (vGCV), the yCD and HSV-1 TKSR39 activate these prodrugs to form 5-fluorouracil (5-FU) and ganciclovir, respectively. 5-FU gets converted to 5-fluoro-uridine monophosphate (5-FUMP) and subsequently to 5-fluoro-deoxyuridine monophosphate (5-FdUMP); 5-FdUMP irreversible inhibits thymidylate synthase, inhibits deoxythymidine triphosphate (dTTP) formation and halts DNA synthesis. Once phosphorylated intracellularly, ganciclovir triphosphate competitively inhibits deoxyguanosine triphosphate (dGTP) incorporation into DNA and inhibits DNA synthesis.
A small molecule immune checkpoint inhibitor of the adenosine A2A receptor (ADORA2A) with potential antineoplastic activity. Upon oral administration, adenosine-A2A receptor antagonist CPI-444 binds to adenosine A2A receptors expressed on the surface of immune cells, including T-lymphocytes, natural killer (NK) cells, macrophages and dendritic cells (DCs). This prevents tumor-released adenosine from interacting with the A2A receptors on these key immune surveillance cells, thereby abrogating adenosine-induced immunosuppression in the tumor microenvironment. This may stimulate anti-tumor immune responses, resulting in tumor regression.
A population of stromal vascular fraction (SVF) cells derived from autologous adipose tissue, with potential tissue regenerative activity. SVF cells are obtained through liposuction and contain multiple cell types, including adipose-derived stem cells (ADSCs), mesenchymal and endothelial progenitor cells, leukocyte subtypes, lymphatic cells, pericytes, and vascular smooth muscle cells. The SVF cells are processed in such a way as to contain a reproducible and consistent composition of heterogeneous cells. Upon processing and administration, the adipose-derived SVF cells can differentiate into different tissue types, support neovascularization, replace cells and repair injured issue.
A preparation of genetically modified allogeneic T-cells transduced with a replication-incompetent, self-inactivating lentiviral vector expressing a hinge-optimized, chimeric antigen receptor (CAR), comprised of a CD28 co-stimulatory signaling domain fused to CD3 zeta, the single-chain variable fragment of CD123 antigen (interleukin-3 receptor alpha chain or IL3RA), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, allogeneic CD123CAR-CD28-CD3zeta-EGFRt-expressing T-lymphocytes are directed to and induce selective toxicity in CD123-expressing tumor cells. CD123 is normally expressed on committed blood progenitor cells in the bone marrow; its overexpression is associated with increased leukemic cell proliferation and aggressiveness. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates detection of the administered T-cells in vivo and can promote elimination of those cells following a cetuximab-induced antibody-dependent cellular cytotoxicity (ADCC) response. The costimulatory signaling domain enhances both proliferation of T-cells and antitumor activity. Hinge optimization prevents recognition of the CAR by Fc receptors (FcRs).
An orally bioavailable, selective and reversible inhibitor of human neutrophil elastase (NE), with potential anti-inflammatory activity. Upon administration, alvelestat binds to and inhibits the activity of human NE. This inhibits NE-mediated inflammatory responses, which may prevent lung inflammation and injury, and may improve lung function associated with NE-induced respiratory diseases. NE, a serine protease released by neutrophils during inflammation, is upregulated in a number of respiratory diseases.
A humanized monoclonal antibody directed against the human B-cell-specific cell surface antigen CD20 and fused to the recombinant cytokine, interferon-alpha (IFN-a), with potential antineoplastic and immunomodulating activities. Upon administration of anti-CD20 monoclonal antibody-interferon alpha fusion protein IGN002, the antibody moiety specifically targets and binds to CD20. In turn, the IFN-a moiety binds to the IFN receptor, and activates IFN-mediated signal transduction, which induces the transcription and translation of genes whose protein products mediate anticancer effects. This results in the induction of both G2 cell cycle arrest and apoptosis in CD20-expressing tumor cells. In addition, IGN002 causes the induction of complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) against CD20-expressing B-cells, which leads to B-cell apoptosis and the inhibition of tumor cell proliferation. CD20, a non-glycosylated cell surface phosphoprotein that is exclusively expressed on B-cells during most stages of B-cell development, is often overexpressed in B-cell malignancies.
An antibody-drug conjugate (ADC) consisting of the humanized monoclonal antibody Z4681A conjugated, via a cleavable disulfide linker, to the cytotoxic DNA alkylating agent DGN462, which is an indolino-benzodiazepine dimer containing a mono-imine moiety, with potential antineoplastic activity. The monoclonal antibody portion of anti-CD33 monoclonal antibody-DGN462 conjugate IMGN779 specifically binds to the cell surface antigen CD33 expressed on myeloid leukemia cells; upon internalization, the DGN462 moiety is released, and covalently binds to and alkylates DNA, thereby causing cell cycle arrest, apoptosis and inhibition of cell growth in myeloid leukemia cells that express CD33. CD33 is expressed on normal non-pluripotent hematopoietic stem cells and myeloid leukemia cells.
A monoclonal antibody against the ectoenzyme CD73 (cluster of differentiation 73), also known as 5'-nucleotidase (5'-NT; ecto-5'-nucleotidase) with potential antineoplastic activity. Upon administration, anti-CD73 monoclonal antibody MEDI9447 targets and binds to CD73, leading to clustering of and internalization of CD73. This prevents CD73-mediated conversion of adenosine monophosphate (AMP) to adenosine and decreases the amount of free adenosine. This prevents adenosine-mediated lymphocyte suppression and increases the activity of CD8-positive effector cells. This also activates macrophages, and reduces both myeloid-derived suppressor cells (MDSCs) and regulatory T-lymphocytes. By abrogating the inhibitory effect on the immune system and enhancing the cytotoxic T-cell-mediated immune response against cancer cells, tumor cell growth decreases. In addition, clustering and internalization of CD73 decreases the migration of cancer cells and prevents metastasis. CD73, a plasma membrane protein upregulated on a number of cancer cell types, catalyzes the conversion of extracellular nucleotides, such as AMP, to membrane-permeable nucleosides, such as adenosine; it plays a key role in adenosine-mediated immunosuppression within the tumor microenvironment.
A human bispecific antibody targeting both epidermal growth factor receptor EGFR and hepatocyte growth factor receptor (HGFR; cMet), with potential antineoplastic activity. Upon administration, anti-EGFR/c-Met bispecific antibody JNJ-61186372 simultaneously targets and binds to wild-type or certain mutant forms of both EGFR and cMet expressed on cancer cells, thereby preventing receptor phosphorylation. This prevents the activation of both EGFR- and cMet-mediated signaling pathways. In addition, binding results in receptor degradation, which further inhibits EGFR- and cMet-mediated signaling. JNJ-61186372 also causes antibody-dependent cellular cytotoxicity (ADCC). Altogether, this results in the inhibition of tumor cell proliferation. EGFR and cMet, both upregulated or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation.
An antibody-drug conjugate (ADC) composed of a human monoclonal antibody against the fibroblast growth factor receptor type 3 (FGFR3) that is conjugated to an undisclosed cytotoxic agent, with potential antineoplastic activity. Upon administration, the antibody moiety of anti-FGFR3 ADC LY3076226 binds to FGFR3. Upon internalization, the cytotoxic moiety causes cell death in FGFR3-expressing tumor cells. FGFR3, a receptor tyrosine kinase upregulated or mutated in many tumor cell types, plays a key role in tumor cell proliferation.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (EGFR2; HER2) site-specifically conjugated, via the non-natural amino acid linker para-acetyl-phenylalanine (pAcF), to the auristatin analog and potent microtubule inhibitor monomethyl auristatin F (MMAF), with potential antineoplastic activity. Upon administration of anti-HER2 ADC ARX788, the antibody moiety targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, MMAF binds to and inhibits tubulin polymerization, which results in G2/M phase arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. The site-specific conjugation of the cytotoxic agent to the antibody improves the biophysical properties of ARX788, increases payload stability and optimizes its efficacy.
A human monoclonal antibody against the pro-inflammatory mediator interleukin-8 (IL-8; CXCL8), with potential antineoplastic activities. Upon administration, HuMax-IL8 directly binds to IL-8, thereby inhibiting the binding of IL-8 to its receptors CXCR1 and CXCR2. This inhibits activation of IL-8-mediated signaling transduction pathways, which decreases proliferation of susceptible tumor cells. Also, HuMax-IL8 effectively blocks binding of IL-8 to neutrophils and inhibits neutrophil activation and recruitment towards sites of inflammation, which reduces inflammation. IL-8, a member of the CXC chemokine family, is upregulated in a variety of cancer cell types and inflammatory diseases; it plays a key role in tumor cell proliferation, endothelial cell proliferation, and cancer stem cell (CSC) renewal.
A humanized monoclonal antibody against the immune receptor human killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 (KIR3DL2), with potential immunomodulating and antineoplastic activities. Upon administration, the anti-KIR3DL2 monoclonal antibody IPH4102 binds to KIR3DL2 expressed on certain tumor cells. This recruits natural killer (NK) cells and leads to lysis of KIR3DL2-expressing tumor cells. In addition, IPH4102 induces antibody-dependent cellular cytotoxicity (ADCC), thereby further eliminating tumor cells. KIR3DL2, a tumor-associated antigen (TAA) and inhibitory receptor of the KIR family, is specifically expressed in most subtypes of cutaneous T-cell lymphomas (CTCL) and expressed only on a fraction of normal NK cells.
An agonistic humanized immunoglobulin G1 (IgG1) monoclonal antibody against the cell surface receptor OX40 (CD134; TNFRSF4), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-OX40 monoclonal antibody GSK3174998 selectively binds to and activates OX40. Receptor activation induces proliferation of memory and effector T-lymphocytes and results in a T-cell-mediated immune response against tumor cells, which leads to tumor cell lysis. OX40, a cell surface glycoprotein and member of the tumor necrosis factor receptor superfamily (TNFRSF), is expressed on T-lymphocytes and provides a co-stimulatory signal that promotes both the proliferation and survival of activated T-cells.
An inhibitor of the human inhibitory receptor programmed cell death 1 (PD-1; PDCD1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-1 checkpoint inhibitor PF-06801591 targets and binds to PD-1 and blocks the interaction between PD-1 and its ligands, PD-1 ligand 1 (PD-L1) and PD-1 ligand 2 (PD-L2). This prevents the activation of PD-1 and its downstream signaling pathways. This may restore immune function through the activation of natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs) against tumor cells. PD-1, an inhibitory receptor belonging to the B7-receptor family, is expressed on activated T-lymphocytes, B-cells and NK cells; it functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands, and plays an important role in tumor evasion from host immunity.
A T-cell receptor (TCR)-like monoclonal antibody against PR1, a 9 amino-acid (VLQELNVTV) human leukocyte antigen (HLA)-A2-restricted leukemia-associated antigen (LAA) derived from the myeloid leukemia-associated antigens proteinase 3 (P3) and neutrophil elastase (NE), with potential immunostimulating and antineoplastic activities. Upon administration, anti-PR1/HLA-A2 monoclonal antibody Hu8F4 selectively binds to a combined epitope of the PR1/HLA-A2 complex expressed on acute myeloid leukemia (AML) blasts and leukemic stem cells (LSC), and prevents PR1/HLA-A2-mediated signaling. This induces complement-dependent cytotoxicity (CDC), to a lesser extent, antibody-dependent cell-mediated cytotoxicity (ADCC), and CDC/ADCC-independent cytolysis of myeloid leukemia cells. This results in a reduction of cellular proliferation in PR1/HLA-A2-overexpressing leukemic cells. PR1 in combination with the HLA-A2 molecule is highly expressed on AML blasts and LSCs.
An inhibitor of the inhibitory T-cell receptor T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3; hepatitis A virus cellular receptor 2; HAVCR2), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the anti-TIM-3 checkpoint inhibitor MBG453 binds to TIM-3 expressed on certain immune cells, including tumor infiltrating lymphocytes (TILs). This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis resulting in a reduction in tumor growth. TIM-3, a transmembrane protein expressed on certain T-cells, is associated with tumor-mediated immune suppression.
A humanized immunoglobulin (Ig) G1 monoclonal antibody against the stem cell factor receptor c-Kit (SCFR; KIT; CD117), with potential antineoplastic and anti-allergic activities. Upon administration, the anti-c-KIT monoclonal antibody KTN0158 binds to and inhibits the activation of the cell surface antigen c-Kit. This leads to an inhibition of the activation of c-KIT-mediated signal transduction pathways and inhibits cell proliferation in cancer cells expressing c-Kit. In mast cells, inhibition of c-KIT and c-KIT-mediated signaling prevents mast cell activation, degranulation and subsequent cytokine release. c-Kit, a transmembrane protein and receptor tyrosine kinase, is overexpressed in various cell types, including certain cancer cells and mast cells; it plays a key role in the regulation of cell differentiation and proliferation.
An ointment formulation composed of a purified sheep immunoglobulin G (IgG) antibody against the non-functional form of the purinergic P2X7 receptor (nf-P2X7), with potential antineoplastic activity. Upon topical application of the anti-nf-P2X7 antibody ointment BIL-010t, the antibody binds to nf-P2X7 and inhibits its antiapoptotic activity. This may induce apoptosis and inhibit the growth of nf-P2X7-overexpressing cancer cells. P2X7, an ATP-gated cation-selective channel, plays a role in the induction of apoptosis; nf-P2X7, is upregulated in a variety of cancer cell types while not expressed on normal, healthy cells and is unable to form a large transmembrane, apoptotic pore upon exposure to ATP and prevents apoptosis.
An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody against a tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of ABBV-085 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action.
An antibody-drug conjugate (ADC) consisting of an anti-CD19 humanized monoclonal antibody conjugated, via a cleavable linker comprised of valine-alanine and maleimide, to a cytotoxic, cross-linking agent pyrrolobenzodiazepine (PBD) dimer, which targets DNA minor grooves, with potential antineoplastic activity. Upon administration, the monoclonal antibody portion of anti-CD19-PBD conjugate ADCT-402 targets the cell surface antigen CD19 on various cancer cells. Upon antibody/antigen binding and internalization, the cytotoxic PBD moiety is released. The imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links in the minor groove of DNA and inhibits DNA replication, which inhibits the proliferation of CD19-overexpressing tumor cells. CD19, a transmembrane receptor and tumor-associated antigen (TAA), is expressed on a number of B-cell-derived cancers.
An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody against an unnamed tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of PF-06647020 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action.
An antimetabolite with potential antineoplastic activity. Upon administration, FF-10502 is able to enter the nucleus where it inhibits DNA polymerases, thereby preventing DNA synthesis and halting tumor cell proliferation.
An orally bioavailable, proprietary combination of four agents with potential antineoplastic activity. Although the four agents and their exact mechanisms of action are not publicly known, the components of SM-88 appear, upon oral administration, to work synergistically to increase the amount of free radicals in cancer cells, thereby inducing oxidative stress and selective killing of the cancer cells.
Any agent used in the treatment of Pneumocystis jiroveci pneumonia (PJP), formerly known as Pneumocystis carinii pneumonia (PCP).
A finding of a lack of symmetry between two or more bilateral aligned primary ossific nuclei (ossification centers), typically indicated by greater stain uptake in one or more primary ossification centers as compared to others.
An inhibitor of the serine/threonine protein kinase B-raf (BRAF) and epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Lifirafenib selectively binds to and inhibits the activity of BRAF and certain BRAF mutant forms, and EGFR. This prevents BRAF- and EGFR-mediated signaling and inhibits the proliferation of tumor cells that either contain a mutated BRAF gene or express over-activated EGFR. In addition, BGB-283 inhibits mutant forms of the Ras proteins K-RAS and N-RAS. BRAF and EGFR are mutated or upregulated in many tumor cell types.
Any drug or substance that inhibits the activity of tyrosine-protein kinase BTK protein.
A selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), with potential pro-apoptotic and antineoplastic activities. Upon administration, Bcl-2 inhibitor BCL201 binds to and inhibits the activity of Bcl-2. This restores apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in many cancers and plays an important role in the negative regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival.
A nanoparticle-based formulation containing the alkyl ester of bendamustine, a bifunctional mechlorethamine derivative, encapsulated in human serum albumin (HSA), with potential alkylating and antineoplastic activities. Upon administration of the alkyl ester bendamustine-containing nanoparticle formulation RXDX-107, the nanoparticle formulation permits high concentrations of the alkyl ester of bendamustine be localized at the tumor site. The modified bendamustine alkylates and crosslinks macromolecules, resulting in DNA, RNA and protein synthesis inhibition, and, subsequently, apoptosis.
A recombinant dimeric fusion peptide of the human granulocyte colony-stimulating factor (G-CSF; filgrastim), with immunomodulating and hematopoietic activities. Benegrastim binds to the cell surface G-CSF receptors (G-CSFRs) inducing receptor dimerization and activation of signaling cascades such as the Jak-STAT and mitogen-activated protein kinase pathways. This stimulates neutrophil progenitor proliferation and differentiation. Compared to other preparations of monomer recombinant G-CSF, dimeric filgrastim may allow for stronger activation of G-CSFRs and a faster myeloid precursor response thus enhancing neutrophil recovery upon myelosuppressive therapy.
A finding indicating that that an anatomic space or cavity is filled with blood.
A finding that the apex of the tail is rounded or dulled.
A proprietary lotion containing a blend of the four botanicals Allium cepa L. (Onion), Citrus limon L. (Citrus), Theobroma cacao L. (Cocoa), Paullinia cupana (Guarana), with potential activity against chemotherapy-induced alopecia (CIA). Upon administration to the scalp, botanical lotion CG428 may normalize the apoptotic process of hair follicular cells and reduce inflammation in the scalp. This may reverse chemotherapy-induced alopecia (CIA), restore the natural hair cycle, improve hair regrowth, and improve the psychosocial well-being of the affected patient.
Liquid consistency with no solid pieces; indicative of diarrhea.
An orally bioavailable inhibitor of cyclin dependent kinases 2, 5 and 9 (CDK2/5/9), with potential antineoplastic and chemoprotective activities. Upon oral administration, CYC065 selectively binds to and inhibits the activity of CDK2, 5 and 9, which leads to inhibition of CDK2, 5 and 9-dependent cellular pathways, downregulation of genes involved in the pro-survival pathway, prevention of the activation of DNA double-strand break repair pathways, and induction of both cell cycle arrest and apoptosis. This inhibits the proliferation of CDK2/5/9-overexpressing tumor cells. In addition, CYC065 protects hematopoietic stem and progenitor cells (HSPCs), prevents myelosuppression, and preserves the function of the bone marrow. CDKs are serine/threonine kinases involved in the regulation of the cell cycle and may be overexpressed in certain cancer cell types; they play key roles in tumor cell proliferation, the regulation of transcription, and DNA damage repair.
JFK Coma Recovery Scale-Revised (CRS-R) Total score.
Somatic point mutations or frameshift mutations in the CXCR4 gene that result in the truncation of between 10 and 19 amino acid residues from the carboxyl terminus of C-X-C chemokine receptor type 4 protein (CXCR-4) and are associated with Waldenstrom Macroglobulinemia. These mutations are similar to those found in the hereditary disease WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome and encode a constitutively active form of the CXCR-4 protein.
A radioconjugate composed of the orally bioavailable hydrochloride salt form of anlotinib, a receptor tyrosine kinase (RTK) inhibitor, labeled with the radioisotope carbon C 14, with potential use for evaluating the pharmacokinetic profile of anlotinib. Upon administration of carbon C 14 anlotinib hydrochloride, anlotinib targets multiple RTKs, including vascular endothelial growth factor receptor type 2 (VEGFR2) and type 3 (VEGFR3). This agent may both inhibit angiogenesis and halt cell growth in tumor cells that overexpress these RTKs. Labeling of anlotinib with the radioactive tracer carbon C 14 permits the evaluation of this agent's pharmacokinetic profile, including its absorption, distribution, metabolism, and excretion (ADME).
The level of awareness of an organism during a cardiovascular system assessment.
The outcome of the cardiovascular system assessment as originally received or collected.
A finding referring to incomplete or absent chondrogenesis.
A congenital abnormality characterized by the abnormal development of the lower portion of the body. Findings include hypoplastic lower extremities, defects of the caudal vertebrae, sacrum and neural tube, or maldeveloped gastrointestinal or genital organs.
A developmental abnormality characterized by the complex protrusion of viscera outside the abdominal wall.
A radiologic finding indicating the presence of radio-opaque areas in the central parts of lung lobules.
An anaplastic ependymoma that occurs during childhood.
An astrocytoma that occurs during childhood.
An atypical choroid plexus papilloma that occurs during childhood.
A cerebral ganglioneuroblastoma that occurs during childhood.
A choriocarcinoma occurring in children.
An embryonal carcinoma occurring in children.
A nodular ganglioneuroblastoma that occurs during childhood.
A ganglioneuroblastoma that occurs during childhood.
A gastrointestinal stromal tumor (GIST) occurring in childhood. Pediatric GISTs differ biologically from adult GISTs in that only 11% of pediatric GISTs have activating mutations of KIT and PDGFRA.
A germinomatous germ cell tumor occurring in children.
An immature teratoma occurring in children.
A malignant neoplasm that affects the kidney and occurs in childhood.
A mature teratoma occurring in children.
A mixed germ cell tumor occurring in children.
A neuroblastoma that occurs during childhood.
A nongerminomatous germ cell tumor occurring in children.
A mixed germ cell tumor that arises from the ovary and occurs in children.
A nongerminomatous germ cell tumor that arises in the ovary and occurs in children.
A pineal parenchymal tumor of intermediate differentiation that occurs during childhood.
A small intestinal carcinoma occurring in childhood.
A small intestinal leiomyosarcoma occurring in childhood.
An immature teratoma that arises from the testis and occurs in children.
A mature teratoma that arises from the testis and occurs in children.
A non-seminomatous germ cell tumor that arises in the testis and occurs in children.
A follicular thyroid gland carcinoma occurring in childhood.
A medullary thyroid gland carcinoma occurring in childhood.
A papillary thyroid gland carcinoma occurring in childhood. RET/PTC gene rearrangements are more common in children than adults.
A congenital abnormality consisting of a fissure in the midline of the upper jawbone.
An indication as to whether the subject was admitted to a healthcare clinic.
Relapse of multiple myeloma or plasma cell leukemia is defined as follows: Development of new soft tissue plasmacytomas or bone lesions; Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and at least 1 cm) increase as measured serially by the sum of the products of the cross-diameters of the measurable lesion; Hypercalcemia (> 11.5 mg/dL) [2.65 mmol/L]; Decrease in hemoglobin of > 2 g/dL [1.25 mmol/L]; and rise in serum creatinine by 2 mg/dL or more [177 mmol/L or more]. (International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. <http://myeloma.org/ArticlePage.action?articleId=2994>)
A finding in which the walls of a tube or tubular organ have contorted or buckled into its cavity or channel.
A longer-acting antibody directed against terminal complement protein C5, with potential anti-inflammatory activity. Upon administration, complement C5 inhibitor ALXN1210 binds to terminal complement protein C5, thereby blocking C5 cleavage into pro-inflammatory components and preventing the complement-mediated destruction of red blood cells (RBCs) as seen in paroxysmal nocturnal hemoglobinuria (PNH). Compared to other anti-C5 antibodies, ALXN1210 is longer-acting and allows for monthly dosing. C5, a complement pathway protein, is expressed at high levels by the liver.
Absence of residual disease based on pre-defined thresholds and MRD negativity by laboratory techniques.
A mixture composed of curcuminoid phenols extracted from the plant Curcuma longa (turmeric root) with potent antioxidant and anti-inflammatory properties. Curcumin/demethoxycurcumin/bisdemethoxycurcumin-containing supplement is a unique combination of three phenols: curcumin, demethoxycurcumin and bisdemethoxycurcumin. This agent may both prevent the formation of free radicals and neutralize free radicals. Curcuminoids may have chemopreventive and antiproliferative properties. (NCI04)
A finding that the tail is curved or coiled into a circular shape.
A DNA-based combination immunotherapeutic, INO-3112, composed of VGX-3100, a preparation of DNA plasmids encoding the E6 and E7 genes of human papillomavirus (HPV) subtypes 16 and 18, combined with INO-9012, a DNA plasmid encoding the immune activator and pro-inflammatory cytokine human interleukin-12 (IL-12) with potential immunoactivating and antineoplastic activities. Upon intramuscular delivery by electroporation of VGX-3100, the HPV E6 and E7 proteins are translated in cells and elicit a cytotoxic T-lymphocyte (CTL) response against cancer cells expressing the E6 and E7 antigens, resulting in tumor cell lysis. HPV type 16 and HPV type 18 are associated with the development of certain types of cancer. Upon intramuscular delivery by electroporation of INO-9012, IL-12 is expressed and activates the immune system by promoting the activation of natural killer cells (NK cells), inducing secretion of interferon-gamma (IFN-g) and promoting CTL responses against tumor cells. This boosts the immune response and results in increased CTL-mediated tumor cell death as compared with the administration of VGX-3100 alone.
A therapeutic DNA vaccine composed of three parts, one encodes the E6/E7 fusion protein of human papillomavirus (HPV) type 16 (HPV16), the second is a dimerization entity and the third part encodes a protein that specifically binds to antigen presenting cells (APCs), with potential immunostimulating and antineoplastic activities. Upon intramuscular administration, the DNA vaccine VB10.16 expresses HPV16 E6/7 and a protein that targets receptors on APCs. Upon binding to APCs and subsequent internalization, the APCs mature and the HPV16 E6/7 antigenic protein is presented by the APCs. This attracts and stimulates B-lymphocytes, CD4-positive T-lymphocytes and elicits a cytotoxic T-lymphocyte (CTL) response against cancer cells expressing HPV16-associated E6 and E7 oncoproteins, which result in tumor cell lysis. HPV16 E6/7, a viral antigen, plays a key role in the development of certain types of cancer.
An immunoconjugate consisting of an anti-CD19 monoclonal antibody conjugated to the auristatin derivative monomethyl auristatin F (MMAF), with potential antineoplastic activity. Upon administration of denintuzumab mafodotin, the antibody moiety targets the cell surface antigen CD19, found on a number of B-cell-derived cancers. Upon antibody/antigen binding and internalization, the immunoconjugate releases MMAF, which binds to tubulin and inhibits its polymerization. Inhibition of tubulin polymerization may result in G2/M phase arrest and tumor cell apoptosis. This causes inhibition of cell growth of CD19-expressing tumor cells. CD19, a B-cell antigen, is overexpressed by a variety of different cancer cell types.
Mutation located after the C-helix of the tyrosine kinase domain of EGFR.
A nucleotide substitution at position 2303 of the coding sequence of the EGFR gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 768 in the epidermal growth factor receptor protein where serine has been replaced by isoleucine.
An orally bioavailable antagonist of the prostaglandin E receptor subtype 4 (EP4), with potential analgesic, immunomodulating and antineoplastic activities. Upon administration of the EP4 receptor antagonist AAT-007, this agent selectively binds to and inhibits the binding of prostaglandin E2 (PGE2) and prevents the activation of the EP4 receptor. This inhibits PGE2-EP4 receptor-mediated signaling and prevents proliferation in tumor cells in which the PGE2-EP4 signaling pathway is over-activated. In addition, EP4 receptor inhibition modulates the immune system by preventing both interleukin-23 (IL-23) production and the IL-23-mediated expansion of Th17 cells. As EP4 is expressed by peripheral sensory neurons, blockade of EP4-mediated signaling may induce an analgesic effect. EP4, a prostanoid receptor subtype, is a G protein-coupled receptor that is expressed in certain types of cancers; it promotes tumor cell proliferation and invasion.
A birth event that occurs prior to the scheduled c-section date or expected delivery date.
A death of the embryo occurring inside the uterus.
An implantation site that contains no discernible embryonic or placental tissue but may contain remnants of the implantation.
An orally bioavailable inhibitor of the tyrosine kinases tropomyosin receptor kinases (Trk) A, B and C, C-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK), with potential antineoplastic activity. Upon administration, entrectinib binds to and inhibits TrkA, TrkB, TrkC, ROS1 and ALK. Inhibition of these kinases may result in a disruption of TrkA-, TrkB-, TrkC-, ROS1-, and ALK-mediated signaling. This leads to an induction of apoptosis and an inhibition of tumor cell proliferation in tumor cells that express these kinases. TrkA, TrkB, TrkC, ROS1 and ALK are overexpressed in a variety of cancer cell types.
An orally available hydroxyamidine and inhibitor of indoleamine 2,3-dioxygenase (IDO1), with potential immunomodulating and antineoplastic activities. Epacadostat targets and binds to IDO1, an enzyme responsible for the oxidation of tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, INCB024360 increases and restores the proliferation and activation of various immune cells, including dendritic cells (DCs), NK cells, and T-lymphocytes, as well as interferon (IFN) production, and a reduction in tumor-associated regulatory T cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may inhibit the growth of IDO1-expressing tumor cells. IDO1 is overexpressed by a variety of tumor cell types and DCs.
A proprietary biologic that inhibits the transcriptional-promoting activity of E26 transformation-specific (Ets, E-twenty-six) family transcription factors, with potential antineoplastic activity. Although the exact mechanism(s) of action through which this agent exerts its effect has yet to be fully elucidated, upon administration, Ets-family transcription factor inhibitor TK216 inhibits transcriptional activation mediated by Ets family proteins, including the oncogenic Ewing sarcoma breakpoint region 1/Friend leukemia virus integration 1 (EWSR1/FLI1; EWS/FLI1) fusion protein. This agent may both inhibit the malignant downstream effects mediated by genomic rearrangements that result in the overexpression of Ets family transcription factors and decrease tumor cell growth and proliferation. A chromosomal translocation t(11;22)(q24;q12) fuses the EWSR1 gene and the FLI1 gene and encodes the EWSR1/FLI1 fusion protein, which is an oncoprotein expressed by peripheral primitive neuroectodermal (pPNET) tumors.
A worsening of a problem, condition, or disease.
A benign neoplasm containing two or more cell types arising from the mesenchymal and epithelial components.
A sex cord-stromal tumor that arises from the testis or ovary and does not metastasize.
A benign polyp with prominent, hyperplastic glandular structures.
A smooth muscle neoplasm with malignant charcateristics that arises from the mesovarium.
A malignant sex cord-stromal neoplasm that arises from the testis or ovary and is composed of a mix of cell types.
A carcinoma that arises from neuroepithelial tissues of the olfactory epithelium.
A malignant mesenchymal neoplasm that arises from a pre-existing benign fibroadenoma.
A benign neoplasm arising from the submucosa and composed of large eosinophilic epithelioid and spindle cells. (INHAND)
An abnormal communication between the external auditory canal and the adjacent tissues.
An orally bioavailable inhibitor of human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon oral administration, BLU-554 specifically binds to and blocks the binding of the ligand FGF19 to FGFR4. This prevents the activation of FGFR4, inhibits FGFR4-mediated signaling and leads to an inhibition of tumor cell proliferation in FGFR4-overexpressing cells. FGFR4 is a receptor tyrosine kinase and is involved in tumor cell proliferation, differentiation, angiogenesis, and survival. FGF19 is overexpressed by certain tumor cell types.
Framingham Heart Study Cardiovascular Disease 10-Year Risk Score (FCVD1-Framingham CVD 10-Year Risk Score) Risk score.
Any drug or substance that inhibits the activity of receptor-type tyrosine-protein kinase FLT3 protein.
An indication that something is growing at a fast rate.
Excessive blood loss within the first trimester but prior to onset of labor.
A tag or fold of skin or mucous tissue that extends from an anatomical structure without bony support.
A question about the frequency of an individual's erections.
A synbiotic nutritional supplement containing fructooligosaccharides (FOS), which are linear chains of fructose units that are linked by beta (2-1) bonds, and probiotic cultures of Lactobacillus paracasei (L. paracasei), L. rhamnosus, L. acidophilus and Bifidobacterium lactis (B. lactis), with gastrointestinal (GI) protective and immunomodulating activities. Upon oral administration, the bacteria in this probiotic supplement help maintain adequate colonization of the GI tract and modulate the composition of the normal microflora. Upon colonization of the GI tract, the probiotic bacteria form a protective barrier that helps maintain the integrity of the epithelial barrier. This will interfere with the attachment of pathogenic bacteria and other harmful substances, prevent inflammation and improve GI function. Additionally, the reconstituted microflora may metabolize FOS, which may promote calcium mobilization into the bloodstream by maintaining a neutral pH in the lower gut.
Glasgow Coma Scale-NINDS Version (GCS NINDS Version) Total score.
An agonist of human glucocorticoid-induced tumor necrosis factor receptor (tumor necrosis factor superfamily, member 18; TNFRSF18; GITR), with potential immunomodulating and antineoplastic activities. Upon administration, GITR agonist MEDI1873 binds to GITR found on multiple types of T-cells, thereby inducing both the activation and proliferation of tumor antigen-specific T effector cells. This abrogates the suppression of T effector cells which is induced by inappropriately activated T regulatory cells (Tregs), and activates the immune system to help eradicate tumor cells. GITR, a member of the TNF receptor superfamily, is expressed on the surface of multiple types of immune cells, including regulatory T-cells, effector T-cells, B-cells, dendritic cells (DCs) and natural killer (NK) cells.
A morphologic finding indicating the presence of a malignant tumor composed of germinoma, dysgerminoma, or seminoma germ cells.
A compound containing the traditional Chinese medicine (TCM) ginseng, a herb belonging to the Araliaceae family, with potential antioxidant, chemopreventive, anti-inflammatory and antineoplastic activities. Upon administration of the ginseng compound, the active ingredients, mainly ginsenosides, inhibit various signal transduction pathways that play key roles in carcinogenesis and inflammation. This leads to the induction of apoptosis in and inhibits proliferation of tumor cells. In addition, ginsenosides enhance the activity of various antioxidant enzymes, induce nitric oxide (NO) formation, inhibit the formation of reactive oxygen species (ROS) and protect against free radical-induced DNA damage. Ginseng also modulates various components of the immune system, including the activation of dendritic cells (DCs).
An antagonist of both glycine transporter type 2 (GlyT2) and serotonin receptor 2A (5HT2A), with potential anti-nociceptive activity. Upon administration, GlyT2/5HT2A antagonist VVZ-149 binds to and blocks both GlyT2 and 5HT2A. Blockage of GlyT2 prevents the re-uptake of the inhibitory neurotransmitter glycine in the synaptic cleft, thereby potentiating glycine-mediated inhibitory signaling, and inhibiting the firing of neurons, which suppresses the transmission of pain signals to the brain and induces analgesia. Blockage of 5HT2A prevents both the binding of its ligand serotonin and 5HT/5HT2A-mediated signaling. This also suppresses pain signaling and induces analgesia. GlyT2 and 5HT2A play key roles in the induction and transmission of pain signals. GlyT2, a glycine plasma membrane transporter, modulates glycine-mediated inhibition of synaptic transmission in the spinal cord and mediates pain signal transmission to the brain; inhibition of GlyT2 potentiates glycinergic mediated pain signaling. Serotonin and its 5HT2A receptor are involved in both serotonin receptor-mediated signaling and the perception of pain.
Formation of a blood clot (thrombus) in the lumen of the vein that carries blood away from the testis or ovary.
The amount of maternal body weight gained over a period of time where the weight at the end of the interval is adjusted for the gravid uterus weight. This is derived by subtracting the maternal body weight adjusted for the gravid uterus from the total maternal body weight.
A condition characterized by the absence of either lateral half of a sternebra.
Formation of a blood clot (thrombus) in the lumen of the veins in the liver or hepatic artery.
Pathology analysis not related to the pathologic prescreen review determined a specific histological subtype that is different from the original pathology report.
The pathologic prescreen review for this project determined that the histologic subtype is different from the pathology report.
A finding that the tail has an approximate 180 degree bend or curve.
An orally bioavailable traditional Chinese medicine (TCM) composed of a granule containing an aqueous extract of Trametes robiniophila murr (Huaier), a mushroom found on hardwood tree trunks, with potential antineoplastic and anti-angiogenic activities. Although the exact mechanism of action through which Huaier exerts its effects is largely unknown, upon administration, this agent induces cell cycle arrest and apoptosis, and inhibits proliferation and migration of susceptible cancer cells through the modulation of various signal transduction pathways involved in carcinogenesis and angiogenesis.
Having a chromosomal number greater than the normal diploid number, with the status of chromosomes 4 and 10 unknown.
Describes areas on an x-ray or CT scan that show up as whiter or brighter than normal.
An orally available, small molecule, antagonist of MDM2 (mouse double minute 2; Mdm2 p53 binding protein homolog), with potential antineoplastic activity. Idasanutlin binds to MDM2 blocking the interaction between the MDM2 protein and the transcriptional activation domain of the tumor suppressor protein p53. By preventing the MDM2-p53 interaction, p53 is not enzymatically degraded and the transcriptional activity of p53 is restored. This may lead to p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger nuclear phosphoprotein and negative regulator of the p53 pathway, is often overexpressed in cancer cells and has been implicated in cancer cell proliferation and survival.
A molecular abnormality indicating the presence of gene rearrangement(s) of the immunoglobulin heavy chain (IGH) locus in the regions encoding the diversity and/or joining regions.
A molecular abnormality indicating the presence of gene rearrangement(s) of the IGH locus in the regions encoding the variable, diversity and/or joining regions.
The condition of an implantation site, embryo, or fetus based on examination.
A subjective score of 1 on a scale that ranges from 0: Not at all important to 4: Extremely important.
A subjective score of 2 on a scale that ranges from 0: Not at all important to 4: Extremely important.
A subjective score of 3 on a scale that ranges from 0: Not at all important to 4: Extremely important.
The inconsistency was caused because macrodissection was performed at the tissue source site to select a region containing an acceptable diagnosis, and the sample histological subtype of the resulting sample was different from the original pathology report.
A cytogenetic abnormality that refers to the allelic gain of an internal part of chromosome 21. It is a rare high-risk chromosomal abnormality that occurs in approximately 2-5% of pediatric patients with B-cell precursor Acute Lymphoblastic Leukemia. This abnormality has been associated with a poor outcome in patients treated by standard protocols.
A radioimmunoconjugate of tenatumomab, a murine monoclonal antibody targeting the tumor-associated antigen (TAA) tenascin-C (TNC), labeled with iodine I 131, with potential antineoplastic activity. The antibody moiety of iodine I 131 tenatumomab binds to TNC, thereby delivering a cytotoxic dose of iodine I 131 specifically to tumors expressing TNC. TNC, an extracellular matrix protein, is upregulated in a variety of tumor cell types; it plays a key role in invasion, tumor cell proliferation and immune evasion.
An ossification site not localized to the main ossification area, as indicated by staining, but is still considered to be within the margins of a normal bone precursor.
Any substance that inhibits JAK2 tyrosine protein kinase, an enzyme that phosphorylates the hydroxyl group of tyrosine on various proteins in various signaling cascades.
An orally bioavailable switch pocket control inhibitor of wild-type and mutated forms of the tumor-associated antigens (TAA) mast/stem cell factor receptor (SCFR) KIT and platelet-derived growth factor receptor alpha (PDGFR-alpha; PDGFRa), with potential antineoplastic activity. Upon oral administration, DCC-2618 targets and binds to both wild-type and mutant forms of KIT and PDGFRa specifically at their switch pocket binding sites, thereby preventing the switch from inactive to active conformations of these kinases and inactivating their wild-type and mutant forms. This abrogates KIT/PDGFRa-mediated tumor cell signaling and prevents proliferation in KIT/PDGFRa-driven cancers. DCC-2618 also inhibits several other kinases, including vascular endothelial growth factor receptor type 2 (VEGFR2; KDR), angiopoietin-1 receptor (TIE2; TEK), PDGFR-beta and macrophage colony-stimulating factor 1 receptor (FMS; CSF1R), thereby further inhibiting tumor cell growth. KIT and PDGFRa are tyrosine kinase receptors that are upregulated or mutated in a variety of cancer cell types; mutated forms play a key role in the regulation of tumor cell proliferation and resistance to chemotherapy.
A syndrome caused by Kaposi sarcoma-associated herpesvirus (KSHV) infection. It manifests with fever, weight loss, and fluid retention in the legs or abdomen. Patients are at risk of developing KSHV-related cancers including Kaposi sarcoma and lymphoma.
A finding that the tail has a localized undulation.
A locked nucleic acid (LNA)-based oligonucleotide inhibitor of microRNA (miRNA) 155 (miR-155), with potential antineoplastic activity. Upon administration, LNA-based anti-miR-155 MRG-106 targets, binds to and inhibits miR-155. This silences miR-155 and prevents the translation of certain tumor promoting genes, which leads to the induction of cancer cell apoptosis and the inhibition of tumor cell growth. miR-155, an oncogenic single-stranded, non-coding RNA that is critical to the regulation of gene expression, is overexpressed in certain tumor cell types. Up-regulation of miR-155 plays a key role in increased tumor cell proliferation and survival. The LNA is an RNA analog in which the ribose ring is locked in a particular confirmation that increases stability. Compared to the unmodified oligonucleotide, the LNA-modified oligonucleotide shows increased affinity for its target miR-155.
A liposome-encapsulated formulation of bupivacaine, which is an amide-type, long-acting local anesthetic. Upon administration, bupivacaine reversibly binds to specific sodium ion channels in the neuronal membrane, resulting in both a decrease in the voltage-dependent membrane permeability to sodium ions and membrane stabilization. This leads to inhibition of both depolarization and nerve impulse conduction, and a reversible loss of sensation. Compared to bupivacaine alone, liposomal delivery increases the duration of local anesthetic action and delays the peak plasma concentration of bupivacaine due to its slow release from the liposome.
A measurement of the concentration of iron in the liver as an estimate of body iron load.
A soluble, recombinant fusion protein composed of a modified form of the extracellular domain of human activin receptor type IIb (ActRIIb) and linked to the human IgG1 Fc domain, with red blood cell stimulating activity. Upon subcutaneous administration, luspatercept inhibits several ligands in the transforming growth factor (TGF)-beta superfamily. This prevents activation of a variety of TGF-beta superfamily members involved in late stage erythropoiesis and results in an increased differentiation and proliferation of erythroid progenitors. luspatercept acts at a different, later stage than erythropoietin. This agent ultimately enhances red blood cell production and prevents anemia.
An orally bioavailable inhibitor of mitogen-activated protein kinase (MAPK)-interacting serine/threonine-protein kinase 1 (MNK1) and 2 (MNK2), with potential antineoplastic activity. Upon oral administration, MNK1/2 inhibitor eFT508 binds to and inhibits the activity of MNK1 and 2. This prevents MNK1/2-mediated signaling, and inhibits the phosphorylation of certain regulatory proteins, including eukaryotic translation initiation factor 4E (eIF4E), that regulate the translation of messenger RNAs (mRNAs) involved in tumor cell proliferation, angiogenesis, survival and immune signaling. This inhibits tumor cell proliferation in MNK1/2-overexpressing tumor cells. MNK1/2 are overexpressed in a variety of tumor cell types and promote phosphorylation of eIF4E; eIF4E is overexpressed in many tumor cell types and contributes to tumor development, maintenance and resistance.
The pressure and/or displacement of adjacent tissues that results from the growth of a mass.
A suspension of autologous tumor-derived microparticles (ATMP), that are harvested from a patient with malignant pleural effusion, encapsulating the antimetabolic drug methotrexate (MTX), with potential anticancer activity. Although the exact mechanism(s) of action through which this agent exerts its effect has yet to be fully elucidated, upon administration of MTX-ATMP, the MTX moiety is released and internalized by tumor cells. It then binds to and inhibits the enzyme dihydrofolate reductase. This results in the inhibition of purine nucleotide synthesis and leads to decreased synthesis of both DNA and RNA, which induces cell death. Presumably, the encapsulation of MTX by the ATMP improves its bioavailability and decreases its toxicity.
A dendritic cell (DC)-based vaccine composed of program death ligands 1 and 2 (PDL1/L2)-silenced DCs and loaded with the recipient's minor histocompatibility antigens (MiHA), with potential use for graft-versus-tumor (GVT) induction following allogeneic stem cell transplantation (allo-SCT). Donor DCs are electroporated ex vivo with MiHA mRNA and small interfering RNAs (siRNAs) designed to silence the expression of PD L1/L2. After allo-SCT and upon intravenous administration of the MiHA-loaded PD-L1/L2-silenced DC vaccine, the DCs induce the expansion and activation of MiHA-specific CD8-positive T-cells. These tumor antigen-reactive T-cells exert their GVT effect by killing miHA-positive tumor cells. PD-L1/L2, co-inhibitory ligands expressed on DCs, play key roles in preventing MiHA-specific CD8-positive T-cell expansion; silencing enhances MiHA-specific CD8-positive T-cell expansion and activity and improves the GVT effect. The MiHA are human leukocyte antigen (HLA)-bound peptides and are exclusively expressed by the recipient's hematopoietic tumor cells.
A description or characterization of the duration of a microscopic finding.
A radiologic finding that describes the movement of the brain beyond the center line.
Absence of residual disease based on laboratory techniques.
Presence of residual disease based on pre-defined thresholds and quantifiable MRD positivity by laboratory techniques.
Presence of residual disease based on pre-defined thresholds and return of quantifiable MRD positivity after a period of MRD negativity.
An assessment of the minimal residual disease response to therapy.
A soluble, thapsigargin prodrug containing the cytotoxic analog of thapsigargin, 8-O-(12Aminododecanoyl)-8-O debutanoylthapsigargin (12-ADT) linked, via a carboxyl group, to the targeting peptide containing aspartic acid with potential antineoplastic activity. Upon intravenous administration, mipsagargin targets prostate specific membrane antigen (PSMA), a type II membrane carboxypeptidase, which is overexpressed in prostate cancer cells and in the neovasculature of most solid tumors but not in normal blood vessels. Mipsagargin is subsequently converted, through hydrolysis, into the active cytotoxic analog of thapsigargin 12-ADT-Asp. 12-ADT binds to and blocks the Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase (SERCA) pump, thereby increasing the concentration of cytosolic calcium which leads to an induction of apoptosis. By preventing nutrient supply to tumor cells, G-202 may be able to inhibit tumor growth. Compared to thapsigargin alone, thapsigargin prodrug G-202 is able to achieve higher concentrations of the active agents at the tumor site while avoiding systemic toxicity.
A third generation, cationic, lipophilic, manganese (Mn) and porphyrin-based mimetic of the human mitochondrial manganese superoxide dismutase (MnSOD), with antioxidant and potential chemoprotective activities. Upon administration, MnSOD mimetic BMX-001 is internalized by cells and mimics the activity of MnSOD by scavenging reactive oxygen species (ROS), such as superoxide anion, hydrogen peroxide, and hydroxyl radical. This prevents oxidative damage to macromolecules such as DNA and minimizes oxygen free radical-related chemotoxicity in normal tissues. This agent was designed to be more lipophilic and less toxic than first and second generation Mn-porphyrin mimetics.
A humanized immunoglobulin G4 (IgG4) monoclonal antibody against the human natural killer (NK) and T-lymphocyte cell checkpoint inhibitor killer cell lectin-like receptor subfamily C member 1 (NKG2A), with potential antineoplastic activity. Upon administration, monalizumab binds to NKG2A and prevents the binding of NKG2A to its ligand human leukocyte antigen-E (HLA-E), which is overexpressed on tumor cells. This blocks the HLA-E-mediated inhibition of NKG2A-positive infiltrating NK and cytotoxic T-lymphocytes (CTLs) and induces a NK and CTL-mediated immune response against the cancer cells leading to their destruction. Human NKG2A, an inhibitory cell surface receptor covalently bound to CD94, is expressed by NK cells and CTLs. Stimulation of the CD94/NKG2A complex inhibits the cytotoxic activity of these cells. HLA-E, a nonclassical HLA class Ib molecule, is often overexpressed on tumor cells and is associated with poor prognosis.
The agent, stimulus, activity, or event that causes stress with an acute frequency, which has the highest level of severity.
The agent, stimulus, activity, or event that causes stress with a chronic frequency, which has the highest level of severity.
A carcinoma arising from the epithelium of the renal parenchyma or the renal pelvis of a mouse.
Plasma cell myeloma occurring in a mouse.
A mouse chromosomal abnormality consisting of the presence of a third copy of chromosome 16 in somatic cells. Mice that are trisomic for chromosome 16 offer a genetic model for studies relevant to Down syndrome.
A lysosomal storage disease characterized by multiple bone formation abnormalities, progressive joint stiffness, developmental abnormalities, hearing loss, hepatosplenomegaly, increased acne, enlarged tongue, and cornea clouding due to accumulation of lipid substances.
A cancer vaccine composed of a combination of the injectable formulations S-488210, which contains the three HLA-A*02:01-restricted peptides up-regulated lung cancer 10 (lymphocyte antigen 6K; LY6K; URLC10), cell division cycle-associated protein 1 (kinetochore protein Nuf2; NUF2; CDCA1) and insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3; KOC1) and S-488211, which contains the two HLA-A*02:01-restricted peptides DEP domain-containing protein 1A (DEPDC1) and M-phase phosphoprotein 1 (kinesin-like protein KIF20B; MPHOSPH1), with potential immunostimulatory and antitumor activities. Upon administration, multipeptide vaccine S-588210 may stimulate a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing KOC1, CDCA1, URLC10, DEPDC1 or MPHOSPH1 peptides, resulting in tumor cell lysis and decreased tumor growth.
A radiologic finding indicating the presence of a solitary, round, circumscribed shadow in the lung on chest x-ray.
A subjective answer of non-agreement regarding the certainty of something.
A subjective answer of weak agreement regarding the certainty of something.
An agent that targets p-cadherin (CDH3), with potential antineoplastic activity. Upon administration, PF-06671008 binds to and inhibits the activity of p-cadherin; this may inhibit both invasion and proliferation of p-cadherin expressing tumor cells. P-cadherin, a cell-surface protein and member of the cadherin family, is overexpressed in a variety of tumors and plays a role in cell adhesion, motility, invasion, and proliferation.
An agent designed to interfere with the activity of programmed cell death protein 1 (PD1). PD1 inhibitors block T-cell apoptosis and act as non-specific activators of the immune system.
An orally bioavailable inhibitor of specific mutated forms of platelet-derived growth factor receptor alpha (PDGFR alpha; PDGFRa) and mast/stem cell factor receptor c-Kit (SCFR), with potential antineoplastic activity. Upon oral administration, BLU-285 specifically binds to and inhibits specific mutant forms of PDGFRa and c-Kit, including the PDGFRa D842V mutant and various KIT exon 17 mutants. This results in the inhibition of PDGFRa- and c-Kit-mediated signal transduction pathways and the inhibition of proliferation in tumor cells that express these PDGFRa and c-Kit mutants. PDGFRa and c-Kit, protein tyrosine kinases and tumor-associated antigens (TAAs), are mutated in various tumor cell types; they play key roles in the regulation of cellular proliferation.
Patient Health Questionnaire - 15 (PHQ-15) Total score.
An orally bioavailable inhibitor of the delta isoform of phosphatidylinositide 3-kinase (PI3K), with potential antineoplastic activity. Upon oral administration, PI3K-delta inhibitor ME-401 selectively inhibits the delta isoform of PI3K and prevents the activation of the PI3K/AKT signaling pathway. This both decreases proliferation and induces cell death in PI3K-delta-overexpressing tumor cells. PI3K-delta plays a key role in the proliferation and survival of hematologic cancer cells. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival.
An orally bioavailable, highly selective small molecule inhibitor of the gamma isoform of phosphoinositide-3 kinase (PI3K-gamma) with potential immunomodulating and antineoplastic activities. Upon administration, IPI-549 prevents the activation of the PI3K-gamma-mediated signaling pathways, which may lead to a reduction in cellular proliferation in PI3K-gamma-expressing tumor cells. In addition, this agent is able to modulate anti-tumor immune responses and inhibit tumor-mediated immunosuppression. Unlike other isoforms of PI3K, the gamma isoform is overexpressed in certain tumor cell types and immune cells; its expression increases tumor cell proliferation and survival. By selectively targeting the gamma isoform, PI3K signaling in normal, non-neoplastic cells is minimally or not affected, which results in a reduced side effect profile.
The concentration of prostate specific antigen in a sample.
An orally available, small molecule and selective ATP-competitive pan-inhibitor of proviral integration sites for Moloney murine leukemia virus (PIM) kinases, with potential antineoplastic activity. Upon oral administration, pan-PIM kinase inhibitor INCB053914 binds to and inhibits the activities of the three PIM isoforms, PIM1, PIM2 and PIM3. This prevents phosphorylation of their downstream targets and inhibits proliferation in cells that overexpress PIMs. PIMs, constitutively active proto-oncogenic serine/threonine kinases upregulated in various types of cancers, play key roles in tumor cell proliferation and survival.
A skin lesion characterized by the presence of scaly papules and plaques.
A long-acting, engineered and pegylated version of human granulocyte-colony stimulating factor (G-CSF), with potential hematopoietic activity. Similar to G-CSF, pegfilgrastim anti-neutropenic factor (ANF) binds to and activates specific cell surface receptors, and stimulates neutrophil progenitor proliferation and differentiation. Therefore, this agent may prevent the duration and incidence of chemotherapy-induced neutropenia. Compared to filgrastim, the conjugation with a branched polyethylene glycol molecule reduces renal clearance and increases its plasma half-life.
A synthetic peptide derived from erythropoietin (EPO) linked to polyethylene glycol (PEG), with erythropoietic stimulating activity. Upon administration, pegol sihematide binds to and activates EPO receptors on the surface of erythroid progenitor cells in the bone marrow resulting in their differentiation and proliferation. This increases the production of red blood cells and prevents anemia. Pegylation increases this agent's blood circulation time.
A recombinant modified form of the human enzyme arginase 1 (ARG1), in which cobalt is substituted for manganese as a cofactor, covalently attached to polyethylene glycol (PEG), with potential arginine degrading and antineoplastic activities. Upon intravenous administration of pegylated recombinant human ARG1 AEB1102, ARG1 metabolizes the amino acid arginine to ornithine and urea, thereby lowering blood arginine levels. This normalizes blood arginine levels in patients with ARG1 deficiency and prevents hyperargininemia. This also inhibits the proliferation of cancer cells that are dependent on extracellular arginine uptake for their proliferation. In normal, healthy cells, arginine is synthesized intracellularly by the enzymes ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS), and argininosuccinate lyase (ASL); thus they are not dependent on extracellular arginine for survival. In cancer cells these enzymes are disabled; therefore, this agent may inhibit proliferation and survival of these cells by depleting extracellular arginine. Pegylation improves blood circulation times and cobalt substitution increases the catalytic activity of ARG1.
An orally bioavailable inhibitor of the membrane-bound O-acyltransferase (MBOAT) porcupine (PORCN), with potential antineoplastic activity. Upon oral administration, ETC-1922159 binds to and inhibits PORCN in the endoplasmic reticulum (ER), which blocks post-translational palmitoylation of Wnt ligands and inhibits their secretion. This prevents the activation of Wnt ligands, interferes with Wnt-mediated signaling, and inhibits cell growth in Wnt-driven tumors. Porcupine catalyzes the palmitoylation of Wnt ligands, and plays a key role in Wnt ligand secretion. Wnt signaling is dysregulated in a variety of cancers.
An abnormal flow pattern where the portal venous flow is from the periphery of the liver towards the porta and backwards along the portal vein. It is most typically associated with liver disease.
An orally available protein kinase C (PKC) inhibitor with potential immunosuppressive and antineoplastic activities. Upon oral administration, protein kinase C inhibitor LXS196 binds to and inhibits PKC, which prevents the activation of PKC-mediated signaling pathways. This may lead to the induction of cell cycle arrest and apoptosis in susceptible tumor cells. PKC, a serine/threonine protein kinase overexpressed in certain types of cancer cells, is involved in tumor cell differentiation, proliferation, invasion and survival.
Presence of quantifiable residual disease based on laboratory techniques.
A formulation containing the hydrochloride salt form of the non-imidazole histamine H2 receptor antagonist ranitidine, bismuth potassium citrate, and the hydrate form of sucralfate, a basic aluminum complex of sulfated sucrose, with potential antacid, radio- and cytoprotective activities. Upon oral administration of the ranitidine hydrochloride/bismuth potassium citrate/sucralfate hydrate formulation, ranitidine binds to and blocks the activity of the histamine H2 receptors in the parietal cells in the stomach and in the gastrointestinal (GI) tract, thereby decreasing acid secretion. Sucralfate physically binds to the surface of damaged mucosa, thereby forming a protective barrier that shields the GI tract from stomach acid. It also neutralizes stomach acid. Bismuth inhibits peptic activity, increases mucosal secretions and acts as a barrier to prevent damage by acid. Altogether, this protects against ulcer formation and may help to heal existing ulcers.
Malignant meningioma occurring in a rat. Spontaneously occurring meningiomas in the rat are histologically similar to human meningiomas.
A malignant peripheral nerve sheath tumor occurring in a rat.
A subjective score of 0 on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 10 on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 1 on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 2: I think I need to consider quitting some day on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 3 on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 4: I think I should quit but I'm not quite ready on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 5 on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 6: I am thinking about cutting down or quitting on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 7 on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 8: I have cut down or am seriously thinking of quitting on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
A subjective score of 9 on a scale that ranges from 0: I am not ready to quit to 10: I am ready to quit now.
The reemergence of myelodysplastic syndrome after a period of remission.
Clinical and/or laboratory evidence of reemergence of a malignancy after a period of remission.
A pregnancy result for a female that had all intrauterine deaths.
The level of awareness of an organism during a respiratory system assessment.
The outcome of the respiratory system assessment as originally received or collected.
Lack of the prior infectious complications or malignancy that preceded a transplant
Reynolds Cardiovascular Disease 10-Year Risk Score (Reynolds CVD 10-Year Risk Score) Risk score.
A soluble recombinant antibody-like fusion protein composed of the N-terminal CD47 binding domain of human signal-regulatory protein alpha (SIRPa) linked to the Fc domain of human immunoglobulin G1 (IgG1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the SIRPa-Fc fusion protein TTI-621 selectively targets and binds to CD47 expressed on tumor cells and blocks the interaction of CD47 with endogenous SIRPa, a cell surface protein expressed on macrophages. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of macrophage activation and phagocytosis of cancer cells. This induces pro-phagocytic signaling mediated by the binding of calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein-1 (LRP-1), expressed on macrophages, and results in macrophage activation and the specific phagocytosis of tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, thereby allowing cancer cells to proliferate.
A molecular genetic abnormality that refers to the mutation of the SMO gene located on chromosome 7q32.3.
An antibody drug conjugate containing the humanized monoclonal antibody, hRS7, against tumor-associated calcium signal transducer 2 (TACSTD2 or TROP2) and linked to the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), with potential antineoplastic activity. The antibody moiety of sacituzumab govitecan selectively binds to TROP2. After internalization and proteolytic cleavage, SN-38 selectively stabilizes topoisomerase I-DNA covalent complexes, resulting in DNA breaks that inhibit DNA replication and trigger apoptosis. TROP2, also known as epithelial glycoprotein-1 (EGP-1), is a transmembrane calcium signal transducer that is overexpressed by a variety of human epithelial carcinomas; this antigen is involved in the regulation of cell-cell adhesion and its expression is associated with increased cancer growth, aggressiveness and metastasis.
A condition found in some polyzygotic pregnancies where two or more fetuses share a single placenta.
A traditional Chinese medicine (TCM) decoction containing a mixture of Aconiti lateral root, Zingiberis (ginger) root, Fu Ling (Poria), Atractylodis macrocephalae, Chaenomelis fruit (flowering quince fruit), magnolia bark, Aucklandia costus root, Arecae pericarpium, Tsao-Ko (cardamon) fruit, and licorice root, and may also contain Arecae seeds and Ziziphus jujuba fruit (red date), which may be used to treat edema. Although the exact mechanism(s) of action through which Shi Pi Yin decoction exerts its effect has yet to be fully elucidated, upon oral administration, this TCM may reduce edema.
An indication that something is growing at a slow rate.
Sutures commonly found within the parietal and occipital bones of the skull due to their multiple ossification centers. These sutures exhibit a zigzag pattern with interdigitations and sclerotic borders similar to, and join and merge with the major sutures.
An extraneous, additional long narrow slit or groove that divides an organ into lobes, or tissues and bone into parts.
A global deterioration of health status providing evidence of disease progression not covered by disease response criteria (eg. RECIST).
A toll-like receptor type 7 and 8 (TLR7/8) agonist with potential immunostimulating and antitumor activities. Upon intratumoral administration, TLR7/8 agonist MEDI9197 binds to and activates TLR7 and 8, thereby stimulating antigen-presenting cells (APCs), including dendritic cells (DCs). Activation of DCs results in the production of proinflammatory cytokines, and the activation of cytotoxic T-lymphocyte (CTL) and B-lymphocyte immune responses. This may cause tumor cell lysis. TLR7 and 8, members of the TLR family, play fundamental roles in the activation of the immune system.
An orally available, small molecule selective and S-adenosyl methionine (SAM) competitive inhibitor of histone methyl transferase EZH2, with potential antineoplastic activity. Upon oral administration, tazemetostat selectively inhibits the activity of both wild-type and mutated forms of EZH2. Inhibition of EZH2 specifically prevents the methylation of histone H3 lysine 27 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased tumor cell proliferation in EZH2 mutated cancer cells. EZH2, which belongs to the class of histone methyltransferases (HMTs), is overexpressed or mutated in a variety of cancer cells and plays a key role in tumor cell proliferation.
An orally bioavailable small-molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Tesevatinib binds to and inhibits several tyrosine receptor kinases that play major roles in tumor cell proliferation and tumor vascularization, including epidermal growth factor receptor (EGFR; ERBB1), epidermal growth factor receptor 2 (HER2; ERBB2), vascular endothelial growth factor receptor (VEGFR), and ephrin B4 (EphB4). This may result in the inhibition of tumor growth and angiogenesis, and tumor regression.
Excessive blood loss within the third trimester but prior to onset of labor.
A proprietary synthetic oligonucleotide-based agonist of toll-like receptor 9 (TLR9), with potential immunostimulating activity. Upon administration, TLR9 agonist IMO-2125 binds to and activates TLR9 expressed by plasmacytoid dendritic cells (pDCs) and B-cells. This initiates immune signaling pathways, activates B-cells and pDCs, and induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. TLR9 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.
A question about whether an individual uses or used heroin.
An immunoconjugate consisting of a humanized monoclonal antibody that is engineered to contain cysteine residues that are conjugated to the synthetic, DNA cross-linking, pyrrolobenzodiazepine dimer SGD-1882, via the protease-cleavable linker maleimidocaproyl-valine-alanine dipeptide, with potential antineoplastic activity. The monoclonal antibody portion of vadastuximab talirine specifically binds to the cell surface antigen CD33. This causes the internalization of SGN-CD33A, and the release of the cytotoxic moiety SGD-1882. SGD-1882 binds to and crosslinks DNA, which results in both cell cycle arrest and the induction of apoptosis in CD33-expressing tumor cells. CD33, a transmembrane receptor, is expressed on myeloid leukemia cells.
The point during exercise at which pulmonary ventilation becomes disproportionately high with respect to oxygen consumption.
An indication that something is growing at a very fast rate.
An indication that something is growing at a very slow rate.
A finding that the blood vessels are arising from the same location.
West Haven Hepatic Encephalopathy Grade (West Haven Criteria) Grade.
Hepatocellular carcinoma (HCC) occurring in a woodchuck, usually as a result of chronic infection by the woodchuck hepatitis virus. The woodchuck model of viral-induced HCC provides an animal model that resembles the complex human liver environment of HCC in the context of chronic hepatitis B viral infection.
An orally bioavailable, non-peptidomimetic antagonist of both X chromosome-linked inhibitor of apoptosis protein (XIAP) and cellular IAP 1 (cIAP1), with potential antineoplastic and pro-apoptotic activities. Upon administration, XIAP/cIAP1 antagonist ASTX660 selectively binds to and inhibits the activity of XIAP and cIAP1. This restores and promotes the induction of apoptotic signaling pathways in cancer cells, and inactivates the nuclear factor-kappa B (NF-kB)-mediated survival pathway. XIAP and cIAP1 are overexpressed by many cancer cell types and suppress apoptosis by inhibiting the activity of certain caspases; they promote both cancer cell survival and chemotherapy resistance.
A cell-based product composed of dendritic cells (DCs) pulsed with tumor-associated antigens (TAAs) and devoid of the inhibitory effect of antigen presentation attenuators (iAPA) combined with cytotoxic T-lymphocytes (CTLs) (iAPA-DC/CTL), with potential immunostimulating and antineoplastic activities. DCs are transduced with a viral vector containing small interfering RNAs (siRNAs) against APAs, which prevents the expression of APA genes and inhibits attenuation of antigen presentation. Upon administration of iAPA-DC/CTL, the DCs are able to efficiently present antigens to the immune system, stimulate the immune system against tumor-associated antigens (TAAs) and hyperactivate TAA-specific CTLs and T-helper cells. Also, the iAPA-based DCs inhibit the activity of the T-regulatory cells (Tregs), thereby abrogating their negative effect on CTL activation and preventing their immunosuppressive activity against TAAs. Altogether, this inhibits tumor cell proliferation. Additionally, the administered CTLs induce direct cancer cell lysis. APAs negatively regulate antigen presentation, activate Tregs and their immunosuppressive activity, affect inflammatory cytokine production by DCs, and negatively regulate the immunostimulatory activity of DCs; they have an overall inhibitory effect on the stimulation of the immune system.
A proprietary antisense oligonucleotide targeting a novel non-coding mitochondrial RNA (ncmtRNA), with potential antineoplastic activity. Upon administration, Andes-1537 binds to ncmtRNA, which is overexpressed in rapidly proliferating cells, such as cancer cells, and not expressed in resting cells. This may decrease the expression of the ncmtRNA, which may inhibit cell proliferation and eventually induce apoptosis in susceptible cancer cells. The proprietary mitochondrial RNA (mtRNA) belongs to the family of non-coding RNAs (ncRNA); it contains an inverted repeat (IR) of 815 nucleotides (nt), which can form a covalent link to the 5' end of the mitochondrial 16S ribosomal RNA (16S mtrRNA).
A highly specific covalent inhibitor of human fibroblast growth factor receptor types 1, 2, 3 and 4 (FGFR1-4) with potential antiangiogenic and antineoplastic activities. FGFR1-4 tyrosine kinase inhibitor PRN1371 specifically binds to a conserved cysteine residue in the glycine-rich loop in FGFRs and inhibits their tyrosine kinase activity, which may result in the inhibition of both tumor angiogenesis and tumor cell proliferation, and the induction of tumor cell death. FGFRs are a family of receptor tyrosine kinases, which may be upregulated in various tumor cell types and may be involved in tumor cell differentiation, proliferation and survival, and in tumor angiogenesis. This agent potently inhibits FGFR1-4 but does not inhibit other tyrosine kinases, even those that share the conserved cysteine, which may improve therapeutic responses and decrease toxicity when compared with less selective inhibitors.
An orally available inhibitor of all members of the serine/threonine protein kinase Raf family, with potential antineoplastic activity. Upon administration, pan-RAF inhibitor LXH254 binds to Raf proteins and inhibits Raf-mediated signal transduction pathways. This inhibits proliferation of Raf-overexpressing tumor cells. Raf protein kinases are critical enzymes in the Ras/Raf/MEK/ERK signaling pathway and are upregulated in a variety of cancer cell types. They play key roles in tumor cell proliferation and survival.
A radioconjugate consisting of the somatostatin antagonistic peptide JR11 that is linked, via the chelating agent dodecanetetraacetic acid (DOTA), to the beta-emitting radioisotope lutetium Lu 177, with potential antineoplastic activity and imaging activity during positron emission tomography/computed tomography (PET/CT). Upon administration, lutetium Lu 177-DOTA-JR11 binds to somatostatin receptors (SSTRs), with high affinity for SSTR2, present on the cell membranes of many types of neuroendocrine tumor (NET) cells. Upon binding and internalization, this radioconjugate specifically delivers a cytotoxic dose of beta radiation to SSTR-positive cells. SSTRs have been shown to be present in large numbers on NETs and their metastases, while most normal tissues express low levels of SSTRs.
An intermixed ganglioneuroblastoma that occurs during childhood.
A Traditional Chinese Medicine (TCM) containing Radix Rehmanniae Praeparata, Radix Paeoniae Alba, Radix Astragali, Radix Ginseng, Radix Angelicae Sinensis, and Rhizoma Chuanxiong, with potential immunomodulating activity. Although the exact mechanism of action through which Sheng-Yu-Tang exerts its effect has yet to be fully elucidated, upon oral administration, this TCM may have a beneficial effect on the immune system.
An orally bioavailable inhibitor of the Bromodomain and Extra-Terminal (BET) family of proteins, with potential antineoplastic activity. Upon oral administration, the BET inhibitor GSK2820151 binds to the acetylated lysine recognition motifs in the bromodomains of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth. BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.
An orally available inhibitor of spleen tyrosine kinase (Syk), with potential immunomodulating and antineoplastic activities. Upon oral administration of Syk inhibitor HMPL-523, this agent binds to and inhibits the activity of Syk. This inhibits B-cell receptor (BCR) signaling, which leads to the inhibition of B-cell activation, and prevents tumor cell activation, migration, adhesion and proliferation. Syk, a non-receptor cytoplasmic, BCR-associated tyrosine kinase, is expressed in hematopoietic tissues and is often overexpressed in hematopoietic malignancies; it plays a key role in B-cell receptor signaling.
A recombinant monoclonal antibody against the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF), with potential immunomodulating activity. Upon administration, lenzilumab binds to and neutralizes GM-CSF. This prevents GM-CSF binding to the GM-CSF receptor, which is a heterodimeric protein expressed on myeloid progenitor cells, and prevents GM-CSF-mediated signaling. This may induce apoptosis in and inhibit proliferation of cancer cells that overproduce GM-CSF. GM-CSF plays a key role in the differentiation and proliferation of monocytes, macrophages and granulocytes; elevated levels of GM-CSF are associated with certain autoimmune diseases, inflammatory diseases, and cancers.
A death of the fetus occurring inside the uterus.
A congenital neural tube closure defect resulting in protrusion of the brain, the meninges, and the ventricular system through an opening in the skull, usually involving the squamous part of the occipital bone..
Presence of non-quantifiable residual disease based on laboratory techniques.
An orally bioavailable inhibitor of raptor-mTOR (TOR complex 1 or TORC1) and rictor-mTOR (TOR complex 2 or TORC2) with potential antineoplastic activity. Sapanisertib binds to and inhibits both TORC1 and TORC2 complexes of mTOR, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation. TORC1 and 2 are upregulated in some tumors and play an important role in the PI3K/Akt/mTOR signaling pathway, which is frequently dysregulated in human cancers.
An orally bioavailable agent with potential antineoplastic and anti-vasculogenic mimicry (VM) activities. Although the exact multiple mechanisms of action through which this agent exerts its effects have yet to be fully elucidated, TRX-818, upon oral administration appears to induce cancer cell apoptosis and inhibits cancer cell proliferation. This agent also prevents tumor cell VM by blocking the formation of vasculogenic-like tubular structures through an as of yet undetermined mechanism of action.
A myxopapillary ependymoma that occurs during childhood.
A clinical disease characterised by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells.
Squamous cell carcinoma of the skin which has spread to other anatomic sites.
An adverse event resulting from an immune system reaction to a drug or device. It can affect any organ or system.
Visceral venous thrombosis is an acute, subacute, or chronic complication often occurring in patients with inherited or acquired thrombophilia.
Marginal zone lymphoma which does not respond to treatment.
A carcinoma that arises from the transitional epithelium of the renal pelvis. It is associated with tobacco use and usually presents with gross or microscopic hematuria. Urothelial carcinomas of the renal pelvis are usually of higher grade and higher stage compared to bladder urothelial carcinomas.
A polydeoxyribonucleotide with antithrombotic, thrombolytic, and fibrinolytic properties. Defibrotide induces the release of prostaglandin 12 and reduces the expression of adhesion molecules on endothelial cells, thereby interfering with platelet and leukocyte adhesion to the endothelium. (NCI04)
Sideroblastic anemia-3 is an autosomal recessive hematologic disorder characterized by onset of anemia in adulthood. Affected individuals show signs of systemic iron overload, and iron chelation therapy may be of clinical benefit (summary by Liu et al., 2014). For a discussion of genetic heterogeneity of sideroblastic anemia, see SIDBA1 (300751).
Familial adenomatous polyposis-3 is an autosomal recessive cancer predisposition syndrome characterized by the development of multiple colonic adenomas, often with progression to colorectal cancer. Carcinomas affecting other tissues may also occur, and the carcinomas tend to develop in middle age or late adulthood (summary by Weren et al., 2015). For a discussion of genetic heterogeneity of familial adenomatous polyposis, see FAP1 (175100).
Reducing-body myopathy (RBM) is a rare myopathy characterized pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase (MAG) in the absence of substrate, alpha-glycerophosphate. The term 'reducing body' refers to the reducing activity of the inclusions to nitroblue tetrazolium (NBT) in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies. The clinical features of RBM are variable; a severe form has onset in infancy or early childhood and results in severe disability or early death (RBMX1A; 300717), and a less severe form has onset in late childhood or adulthood (RBMX1B) (summary by Liewluck et al., 2007 and Shalaby et al., 2009).
THPM2 is associated with severe hematopoietic toxicity when patients are treated with standard doses of thiopurines, a class of antineoplastic/immunosuppressant agents that consists of mercaptopurine, thioguanine, and azathioprine. Thiopurines are prodrugs that require extensive metabolism in order to exert their cytotoxic action. Thiopurines are converted into cytotoxic thioguanine nucleotides (TG), which are incorporated into DNA and cause cell death. NUDT15 inactivates thiopurine metabolites and negatively regulates cytotoxicity (summary by Moriyama et al., 2016). The NUDT15 deficiency trait follows an additive genetic mode of inheritance, with the severity of the phenotype proportional to the cumulative number of risk alleles in NUDT15. For a discussion of genetic heterogeneity of poor thiopurine metabolism, see THPM1 (610460).
Infantile hypotonia with psychomotor retardation and characteristic facies-3 is a severe autosomal recessive neurodevelopmental disorder with onset at birth or in early infancy. Most affected individuals show very poor, if any, normal psychomotor development, poor speech, and inability to walk independently (summary by Bhoj et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of infantile hypotonia with psychomotor retardation and characteristic facies, see IHPRF1 (615419).
Complex lethal osteochondrodysplasia of the Symoens-Barnes-Gistelinck type is characterized by severe skeletal osteopenia, microcephaly, multiple fractures, and congenital anomalies including ascites, pleural effusion, and intracranial ventriculomegaly (Symoens et al., 2015).
Autosomal dominant Robinow syndrome (ADRS) is characterized by skeletal findings (short stature, mesomelic limb shortening predominantly of the upper limbs, and brachydactyly), genital abnormalities (in males: micropenis / webbed penis, hypoplastic scrotum, cryptorchidism; in females: hypoplastic clitoris and labia majora), dysmorphic facial features (widely spaced and prominent eyes, frontal bossing, anteverted nares, midface retrusion), dental abnormalities (including malocclusion, crowding, hypodontia, late eruption of permanent teeth), bilobed tongue, and occasional prenatal macrocephaly that persists postnatally. Less common findings include renal anomalies, radial head dislocation, vertebral abnormalities such as hemivertebrae and scoliosis, nail dysplasia, cardiac defects, cleft lip/palate, and (rarely) cognitive delay. When present, cardiac defects are a major cause of morbidity and mortality. A variant of Robinow syndrome, associated with osteosclerosis and caused by a heterozygous pathogenic variant in DVL1, is characterized by normal stature, persistent macrocephaly, increased bone mineral density with skull osteosclerosis, and hearing loss, in addition to the typical features described above.
Nephrotic syndrome type 12 is an autosomal recessive renal disorder caused by defects in the renal glomerular filter. Affected individuals have onset of progressive renal failure in the first years of life. Renal biopsy typically shows focal segmental glomerulosclerosis (FSGS) (summary by Braun et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Advanced sleep phase syndrome is characterized by early sleep time (sleep onset) and early morning awakening (sleep offset) (summary by Zhang et al., 2016). For a discussion of genetic heterogeneity of advanced sleep phase syndrome, see FASPS1 (604348).
Hypomyelinating leukodystrophy-13 is an autosomal recessive neurodegenerative disorder characterized by infantile onset of delayed psychomotor development, axial hypotonia, and spasticity associated with delayed myelination and periventricular white matter abnormalities on brain imaging. More variable neurologic deficits, such as visual impairment, may also occur. Some patients may experience cardiac failure during acute illness (summary by Edvardson et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080.
Individuals with TANGO2-related metabolic encephalopathy and arrhythmias can present in acute metabolic crisis (hypoglycemia, elevated lactate, mild hyperammonemia) or with developmental delay, regression, and/or seizures. The acute presentation varies from profound muscle weakness, ataxia, and/or disorientation to a comatose state. Individuals can present with intermittent acute episodes of rhabdomyolysis. The first episode of myoglobinuria has been known to occur as early as age five months. Acute renal tubular damage due to myoglobinuria can result in acute kidney injury and renal failure. During acute illness, transient electrocardiogram changes can be seen; the most common is QT prolongation. Life-threatening recurrent ventricular tachycardia or torsade de pointes occurs primarily during times of acute illness. Individuals who do not present in metabolic crises may present with gait incoordination, progressively unsteady gait, difficulty with speech, or clumsiness. Intellectual disability of variable severity is observed in almost all individuals. Seizures are observed outside the periods of crises in more than 75% of individuals. Hypothyroidism has been reported in more than one third of individuals.
Common variable immunodeficiency-13 is an autosomal dominant primary immunodeficiency disorder characterized by recurrent bacterial infections, mainly affecting the respiratory tract, and associated with hypogammaglobulinemia and decreased numbers of B cells. The age at onset of clinical features can range from infancy to adulthood, and some patients may have a mild disorder or even remain clinically asymptomatic (summary by Kuehn et al., 2016). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Familial myeloproliferative/lymphoproliferative neoplasms is an autosomal dominant cancer predisposition syndrome characterized by adult-onset of hematologic malignancies mainly affecting the myeloid line. Most patients present with myelodysplastic syndrome (MDS; 614286) and/or acute myeloid leukemia (AML; 601626). Rare lymphoid malignancies, including lymphoma, can also occur. Some mutation carriers, even if unaffected by a hematologic malignancy, may have evidence of immune dysregulation disorders, including asthma, eczema, or juvenile arthritis. The disorder shows incomplete penetrance (summary by Lewinsohn et al., 2016). Patients may show a favorable response to treatment with lenalidomide (summary by Polprasert et al., 2015).
Spinal muscular atrophy with congenital bone fractures is an autosomal recessive severe neuromuscular disorder characterized by onset of severe hypotonia in utero. This results in congenital contractures, consistent with arthrogryposis multiplex congenita, and increased incidence of prenatal fracture of the long bones. Affected infants have difficulty breathing and feeding and often die in the first months or years of life (summary by Knierim et al., 2016). Genetic Heterogeneity of Spinal Muscular Atrophy With Congenital Bone Fractures See also SMABF2 (616867), caused by mutation in the ASCC1 gene (614215) on chromosome 10q22.
Childhood-onset spasticity with hyperglycinemia is an autosomal recessive disorder characterized by onset of slowly progressive spasticity that results in impaired gait in the first decade of life. Imaging of the central nervous system shows leukodystrophy and/or lesions in the upper spinal cord. More variable features include visual defects and mild learning disabilities. Serum glycine is increased, but CSF glycine is only mildly increased or normal; serum lactate is normal. The disorder represents a form of 'variant' nonketotic hyperglycinemia and is distinct from classic nonketotic hyperglycinemia (NKH, or GCE; 605899), which is characterized by significantly increased CSF glycine. Several forms of 'variant' NKH, including SPAHGC, appear to result from defects of mitochondrial lipoate biosynthesis (summary by Baker et al., 2014).
EVEN-PLUS syndrome is characterized by prenatal-onset short stature, vertebral and epiphyseal changes, microtia, midface hypoplasia with flat nose and triangular nares, cardiac malformations, and other findings including anal atresia, hypodontia, and aplasia cutis. The features overlap those reported in patients with CODAS syndrome (600373; Royer-Bertrand et al., 2015).
Scapulohumeroperoneal myopathy is an autosomal dominant muscle disorder characterized by slowly progressive muscle weakness and atrophy affecting both proximal and distal muscles of the upper and lower limbs. Onset is usually in the first decade and can be as early as infancy, although some patients do not notice symptoms until young adulthood. There is marked variability in severity (summary by Zukosky et al., 2015).
Lymphatic malformation-6 is a form of generalized lymphatic dysplasia (GLD), which is characterized by a uniform, widespread lymphedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions. In LMPHM6, there is a high incidence of nonimmune hydrops fetalis (NIHF) with either death or complete resolution of the neonatal edema, but childhood onset of lymphedema with or without systemic involvement also occurs. Mild facial edema is often present. Patients have normal intelligence and no seizures (summary by Fotiou et al., 2015). For a discussion of genetic heterogeneity of lymphatic malformation, see 153100.
Parkinson disease-23 is a progressive neurodegenerative disorder characterized by young-adult onset of parkinsonism associated with progressive cognitive impairment leading to dementia and dysautonomia. Some individuals have additional motor abnormalities. Affected individuals become severely disabled within a few decades (summary by Lesage et al., 2016).
SC4MOL deficiency represents an inborn error of cholesterol metabolism that is characterized by accumulation of a large amount of methylsterols, particularly dimethylsterols, in affected patients. The associated features of immune dysregulation, skin disease, and growth delay can be at least partially corrected with cholesterol and statin supplements (He et al., 2014).
Congenital disorder of glycosylation type IIp (CDG2P) is an autosomal recessive metabolic disorder characterized by mild liver dysfunction, which may be found incidentally during adolescence. Laboratory abnormalities include elevated liver enzymes and alkaline phosphatase, coagulation factor deficiencies, hypercholesterolemia, and low ceruloplasmin. Serum isoelectric focusing of proteins shows a combined defect of N- and O-glycosylation, suggestive of a Golgi defect (summary by Jansen et al., 2016). For an overview of congenital disorders of glycosylation, see CDG1A (212065) and CDG2A (212066).
Congenital disorder of glycosylation type IIo (CDG2O) is an autosomal recessive metabolic disorder characterized by infantile onset of progressive liver failure, hypotonia, and delayed psychomotor development. Laboratory abnormalities include elevated liver enzymes, coagulation factor deficiencies, hypercholesterolemia, and low ceruloplasmin. Serum isoelectric focusing of proteins shows a combined defect of N- and O-glycosylation, suggestive of a Golgi defect (summary by Jansen et al., 2016). For a general discussion of CDGs, see CDG1A (212065).
Autosomal recessive muscular dystrophy with cardiomyopathy and triangular tongue (MDRCMTT) is an autosomal recessive muscle disorder characterized by onset of severe and progressive muscle weakness and atrophy in childhood, resulting in loss of independent ambulation. Patients may also have dilated cardiomyopathy and have macroglossia with a small tip, resulting in a triangular appearance of the tongue (summary by Warman Chardon et al., 2015).
Maternal genes play a critical role in the very early stages of embryonic development because of the lag in transcribing genes derived from the male pronucleus. TLE6 mutations are a rare cause of human female-limited fertility and appear to represent the earliest known human embryonic lethality that is due to a single gene mutation. In affected women, ovulation proceeds normally and the retrieved oocytes appear normal, but zygote formation is severely impaired (Alazami et al., 2015). Genetic Heterogeneity of Preimplantation Embryonic Lethality Preimplantation embryonic lethality-2 (PREMBL2; 617234) is caused by mutation in the PADI6 gene (610363) on chromosome 1p36.
Autosomal recessive limb-girdle muscular dystrophy-25 (LGMDR25) is characterized by slowly progressive onset of proximal lower limb weakness in adulthood. Affected individuals also develop cardiac arrhythmias resulting in syncopal episodes as young adults or later in life (summary by Schindler et al., 2016). For discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy (LGMD), see LGMD2A (253600).
Hyperphosphatasia with mental retardation syndrome-6 (HPMRS6) is an autosomal recessive multisystem disorder characterized by global developmental delay, dysmorphic features, seizures, and congenital cataracts. Severity is variable, and the disorder may show a range of phenotypic and biochemical abnormalities, including increased serum alkaline phosphatase levels (summary by Ilkovski et al., 2015). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis. For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (239300). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Lamb-Shaffer syndrome is a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, and mild dysmorphic facial features. Additional variable skeletal abnormalities may also be present (summary by Nesbitt et al., 2015).
UNC80 deficiency is characterized by hypotonia, strabismus, oral motor dysfunction, postnatal growth deficiency, and developmental delay. The majority of individuals do not learn to walk. All individuals lack expressive language; however, many have expressive body language, and a few have used signs to communicate. Seizures may develop during infancy or childhood. Additional features can include nystagmus, extremity hypertonia, a high-pitched cry, repetitive and self-stimulatory behaviors, constipation, clubfeet, joint contractures, and scoliosis. For most individuals the UNC80 deficiency syndrome is not progressive. Individuals have slow acquisition of skills and do not have a loss of skills suggestive of neurodegeneration.
Spinocerebellar ataxia-42 is an autosomal dominant neurologic disorder characterized predominantly by gait instability and additional cerebellar signs such as dysarthria, nystagmus, and saccadic pursuits. The age at onset and severity of the disorder is highly variable; it is slowly progressive (summary by Coutelier et al., 2015). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Combined oxidative phosphorylation deficiency-28 (COXPD28) is a complex autosomal recessive multisystem disorder associated with mitochondrial dysfunction. The phenotype is variable, but includes episodic metabolic decompensation beginning in infancy that can result in mild muscle weakness, cardiorespiratory insufficiency, developmental delay, or even death. Biochemical studies of patient tissues show variable mitochondrial defects, including decreased activities of respiratory chain enzymes (summary by Kishita et al., 2015). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Mental retardation and distinctive facial features with or without cardiac defects (MRFACD) is an autosomal dominant, complex syndromic neurodevelopmental disorder characterized by delayed psychomotor development, poor speech acquisition, distinctive dysmorphic facial features, including frontal bossing, upslanting palpebral fissures, depressed nasal bridge with bulbous tip, and macrostomia. There is variable penetrance of cardiac malformations, ranging from no malformations to patent foramen ovale to septal defects and/or transposition of the great arteries (summary by Adegbola et al., 2015).
Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy type 2 is a disorder of the small arterial vessels of the brain characterized by stroke, transient ischemic attacks (TIA), cognitive impairment, dementia, balance impairment, gait disturbance, headaches, and/or seizures associated with early confluent or confluent diffuse white matter hyperintensities and sometimes associated with multiple lacunar infarcts and microbleeds. Dilated perivascular spaces with a typical status cribrosum characterized by innumerable dilated Virchow-Robin spaces and resulting in a cribriform change in basal ganglia occur in most patients. CADASIL2 differs from CADASIL1 (125310) by a later age of onset (Verdura et al., 2015).
Spastic paraplegia and psychomotor retardation with or without seizures is an autosomal recessive complex neurodevelopmental disorder with onset in infancy. Affected children show hypotonia followed by severely impaired global development and significant motor disability. Most develop seizures in childhood and have speech delay. Other features, such as ocular abnormalities, foot deformities, hypoplasia of the corpus callosum, and decreased white matter, are more variable (summary by Hollstein et al., 2015).
Autosomal visceral heterotaxy-7 is an autosomal recessive developmental disorder characterized by complex congenital heart malformations and/or situs inversus and caused by defects in the normal left-right asymmetric positioning of internal organs. The phenotype is variable (summary by Guimier et al., 2015). For a discussion of the genetic heterogeneity of visceral heterotaxy, see HTX1 (306955).
Familial Behcet-like autoinflammatory syndrome is an autosomal dominant disorder characterized by ulceration of mucosal surfaces, particularly in the oral and genital areas. Additional more variable features include skin rash, uveitis, and polyarthritis. Symptoms become apparent in the first or second decades. The disorder results from inappropriate activation of inflammatory cytokines; treatment with tumor necrosis factor (TNF; 191160) inhibitors may be beneficial (summary by Zhou et al., 2016).
Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is characterized by thrombocytopenia that progresses to pancytopenia, in association with congenital proximal fusion of the radius and ulna that results in extremely limited pronation and supination of the forearm (summary by Niihori et al., 2015). For a discussion of genetic heterogeneity of radioulnar synostosis with amegakaryocytic thrombocytopenia, see RUSAT1 (605432).
Takenouchi-Kosaki syndrome is a highly heterogeneous autosomal dominant complex congenital developmental disorder affecting multiple organ systems. The core phenotype includes delayed psychomotor development with variable intellectual disability, dysmorphic facial features, and cardiac, genitourinary, and hematologic or lymphatic defects, including thrombocytopenia and lymphedema. Additional features may include abnormalities on brain imaging, skeletal anomalies, and recurrent infections. Some patients have a milder disease course reminiscent of Noonan syndrome (see, e.g., NS1, 163950) (summary by Martinelli et al., 2018).
Hereditary essential tremor-5 is an autosomal dominant neurologic disorder characterized by kinetic, intention, and/or postural tremor mainly affecting the upper limbs. The age at onset and severity are highly variable, even within families (summary by Hor et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of hereditary essential tremor, see ETM1 (190300).
Congenital symmetric circumferential skin creases is characterized by the folding of excess skin, which leads to ringed creases, primarily of the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features (summary by Isrie et al., 2015). For a discussion of genetic heterogeneity of congenital symmetric circumferential skin creases, see CSCSC1 (156610).
Nephrotic syndrome type 11 is an autosomal recessive disorder of the kidney with onset in the first decade of life. The disorder is progressive and usually results in end-stage renal disease necessitating renal transplantation, although some patients may have a slightly milder phenotype (summary by Miyake et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome, see NPHS1 (256300).
Primary ciliary dyskinesia-33 is an autosomal recessive disorder characterized by recurrent upper and lower respiratory infections due to defective ciliary clearance and resulting in chronic lung disease. Some patients may have recurrent ear infections resulting in conductive hearing impairment. Examination of respiratory cilia shows subtle movement defects. Laterality defects have not been reported (summary by Olbrich et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Congenital disorder of glycosylation type IIn (CDG2N) is an autosomal recessive severe multisystem developmental disorder characterized by delayed psychomotor development apparent from infancy, hypotonia, and variable additional features, such as short stature, seizures, visual impairment, and cerebellar atrophy. Serum transferrin analysis shows a CDG type II pattern (summary by Boycott et al., 2015 and Park et al., 2015). For a discussion of genetic heterogeneity of CDG type II, see CDG2A (212066).
Autosomal recessive spinocerebellar ataxia-21 is a neurologic disorder characterized by onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. Affected individuals also have recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis, as well as later onset of a peripheral neuropathy. Mild learning disabilities may also occur (summary by Schmidt et al., 2015).
Rhizomelic chondrodysplasia punctata (RCDP) is a peroxisomal disorder characterized by disproportionately short stature primarily affecting the proximal parts of the extremities, a typical facial appearance including a broad nasal bridge, epicanthus, high-arched palate, dysplastic external ears, and micrognathia, congenital contractures, characteristic ocular involvement, dwarfism, and severe mental retardation with spasticity. Biochemically, plasmalogen synthesis and phytanic acid alpha-oxidation are defective. Most patients die in the first decade of life (summary by Wanders and Waterham, 2005). For a discussion of genetic heterogeneity of rhizomelic chondrodysplasia punctata, see 215100.
WAC-related intellectual disability (ID) is typically characterized by variable degrees of global developmental delay and/or intellectual disability. Behavioral abnormalities including anxiety, attention deficit/hyperactivity disorder, and/or autism spectrum disorder are observed in the majority of older children and adults. Most affected infants have significant but nonspecific features at birth such as neonatal hypotonia and feeding problems. Some affected individuals come to medical attention with respiratory or vision problems. Facial features may be mildly dysmorphic, but are nonspecific. To date, 18 individuals have been identified with WAC-related ID.
In dehydrated hereditary stomatocytosis (DHS), also known as hereditary xerocytosis, red blood cells exhibit altered intracellular cation content and cellular dehydration, resulting in increased erythrocyte mean corpuscular hemoglobin concentration (MCHC) and decreased erythrocyte osmotic fragility. Blood films show various cell shape abnormalities, the most characteristic being the stomatocyte, with a straight or crescent-shaped central pallor (summary by Rapetti-Mauss et al., 2015). For discussion of clinical and genetic heterogeneity of the stomatocytoses, see DHS1 (194380).
Charcot-Marie-Tooth disease type 2Z (CMT2Z) is an autosomal dominant peripheral neuropathy characterized by onset, usually in the first decade, of distal lower limb muscle weakness and sensory impairment. The disorder is progressive, and affected individuals tend to develop upper limb and proximal muscle involvement in an asymmetric pattern, resulting in severe disability late in adulthood (summary by Sevilla et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Charcot-Marie-Tooth disease type 2Y is an autosomal dominant peripheral neuropathy characterized by distal muscle weakness and atrophy associated with length-dependent sensory loss. Most patients have involvement of both the lower and upper limbs. The age at onset and the severity of the disorder are highly variable (summary by Gonzalez et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Charcot-Marie-Tooth disease type 4K is an autosomal recessive demyelinating peripheral neuropathy characterized by onset in the first decade of distal muscle weakness and atrophy associated with impaired distal sensation. Both upper and lower limbs are affected. Affected individuals may also have nystagmus and late-onset cerebellar ataxia. Laboratory studies show increased serum lactate and isolated mitochondrial complex IV deficiency (summary by Echaniz-Laguna et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating Charcot-Marie-Tooth disease, see CMT4A (214400).
Hypomyelinating leukodystrophy-12 is an autosomal recessive neurologic disorder characterized by severely delayed or even lack of psychomotor development that becomes apparent in the first months of life. Patients are markedly disabled, with acquired microcephaly, lack of speech, and often lack of spontaneous movement due to hypotonia and spasticity. Brain imaging shows delayed myelination (summary by Edvardson et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080.
Spastic paraplegia-75 is an autosomal recessive, slowly progressive neurodegenerative disorder characterized by onset of spastic paraplegia and cognitive impairment in childhood (summary by Lossos et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016) For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Spastic tetraplegia, thin corpus callosum, and progressive microcephaly is an autosomal recessive neurodevelopmental disorder characterized by onset of those features and severely impaired global development in early infancy. Most patients are unable to achieve independent walking or speech; some patients have seizures (summary by Srour et al., 2015 and Heimer et al., 2015).
Yuan-Harel-Lupski syndrome is a complex neurodevelopmental disorder characterized by global developmental delay and early-onset peripheral neuropathy. The disorder comprises features of both demyelinating Charcot-Marie-Tooth disease type 1A (CMT1A; 118220), which results from duplication of the PMP22 gene on 17p12, and Potocki-Lupski syndrome (PTLS; 610883), which results from duplication of a slightly proximal region on 17p11.2 that includes the RAI1 gene. These 2 loci are about 2.5 Mb apart. The resultant YUHAL phenotype may be more severe in comparison to the individual contributions of each gene, with particularly early onset of peripheral neuropathy and features of both central and peripheral nervous system involvement (summary by Yuan et al., 2015).
Early infantile epileptic encephalopathy-35 is an autosomal recessive neurodegenerative disorder characterized by onset of seizures in the first months of life associated with essentially no normal development. Brain imaging shows a characteristic pattern consistent with lack of myelination of early structures, including the posterior limb of the internal capsule, brainstem tracts, and tracts to the primary visual and motor cortices. Many patients die in early childhood (summary by Kevelam et al., 2015) For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see 308350.
SLC12A5-related epilepsy of infancy with migrating focal seizures (SLC12A5-EIMFS), reported to date in nine children, is characterized by onset of seizures before age six months and either developmental delay or developmental regression with seizure onset. Of these nine children, six had severe developmental delay with no progress of abilities and three made notable neurodevelopmental progress. Eight had postnatal microcephaly and hypotonia. In most children epilepsy begins as focal motor seizures (typically involving head and eye deviation) that become multifocal and intractable to conventional antiepileptic drugs (AEDs).
Progressive myoclonic epilepsy-10 is an autosomal recessive neurodegenerative disorder characterized by onset of progressive myoclonus, ataxia, spasticity, dysarthria, and cognitive decline in the first decade of life. The severity is variable, but some patients may become mute and bedridden with psychosis (summary by Turnbull et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
Smith-Kingsmore syndrome is a rare autosomal dominant syndromic intellectual disability syndrome characterized by macrocephaly, seizures, umbilical hernia, and facial dysmorphic features including frontal bossing, midface hypoplasia, small chin, hypertelorism with downslanting palpebral fissures, depressed nasal bridge, smooth philtrum, and thin upper lip (Smith et al., 2013; Baynam et al., 2015).
Immunodeficiency-44 is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to viral infections and adverse multisystemic reaction to vaccination in some patients. Affected individuals appear to have defects in mitochondrial fission and fusion (summary by Shahni et al., 2015).
Seizures, cortical blindness, and microcephaly syndrome (SCBMS) is an autosomal recessive neurodevelopmental disorder characterized by microcephaly, early-onset seizures, severely delayed psychomotor development, and cortical blindness. Affected individuals also tend to show poor overall growth with short stature (summary by Ercan-Sencicek et al., 2015).
Porokeratosis is a rare skin disorder characterized by one or more annular plaques with a surrounding raised horny border that spreads centrifugally. Variants of porokeratosis have been described that differ in morphologic shapes, distribution, and clinical course (Schamroth et al., 1997). However, as noted by Sybert (2010), several families with expression of more than one variant of porokeratosis among members, and individuals expressing more than one variant, have been reported, suggesting that the distinctions among these variants may be artificial. Mutations in the FDPS gene have been found to cause multiple types of porokeratosis, which have been described as disseminated superficial actinic porokeratosis (DSAP) and nonactinic disseminated superficial porokeratosis (DSP). For a discussion of genetic heterogeneity of porokeratosis, see 174800.
Senior-Loken syndrome-9 is an autosomal recessive disorder characterized by early-onset nephronophthisis and pigmentary retinopathy. Additional more variable features can include liver defects, skeletal anomalies, and obesity (summary by Bizet et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900.
Charcot-Marie-Tooth disease type 2W is an autosomal dominant neurologic disorder characterized by a peripheral neuropathy mainly affecting the lower limbs and resulting in gait difficulties and distal sensory impairment, although most patients also have upper limb involvement. The age at onset is highly variable, ranging from childhood to late adulthood (summary by Safka Brozkova et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Immunodeficiency-42 is an autosomal recessive primary immunodeficiency characterized by increased susceptibility to mycobacterial and candidal infections beginning in infancy. Patients vaccinated with BCG are particularly at risk for developing disseminated mycobacterial infections (summary by Okada et al., 2015).
Heimler syndrome, which represents the mildest end of the peroxisomal biogenesis disorder spectrum (see PBD1A, 214100), is a rare autosomal recessive disorder characterized by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, and nail abnormalities (Ratbi et al., 2015). For a discussion of genetic heterogeneity of Heimler syndrome, see HMLR1 (234580).
Autosomal dominant cutis laxa-3 is characterized by thin skin with visible veins and wrinkles, cataract or corneal clouding, clenched fingers, pre- and postnatal growth retardation, and moderate intellectual disability. In addition, patients exhibit a combination of muscular hypotonia with brisk muscle reflexes (Fischer-Zirnsak et al., 2015). For a general phenotypic description and discussion of genetic heterogeneity of autosomal dominant cutis laxa, see ARCL1 (123700).
Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Craniosynostosis-6 is a bicoronal form associated with bony defects in the sagittal, metopic, or lambdoid sutures (Twigg et al., 2015). For a discussion of genetic heterogeneity of craniosynostosis, see CRS1 (123100).
Kosaki overgrowth syndrome is characterized by a facial gestalt involving prominent forehead, proptosis, downslanting palpebral fissures, wide nasal bridge, thin upper lip, and pointed chin. Affected individuals are tall, with an elongated lower segment, hands, and feet. Skin is hyperelastic and fragile, and there is progressive neurologic deterioration with white matter lesions on brain imaging (Takenouchi et al., 2015).
Adams-Oliver syndrome is a rare developmental disorder defined by the combination of aplasia cutis congenita of the scalp vertex and terminal transverse limb defects (e.g., amputations, syndactyly, brachydactyly, or oligodactyly). In addition, vascular anomalies such as cutis marmorata telangiectatica congenita, pulmonary hypertension, portal hypertension, and retinal hypervascularization are recurrent findings. Congenital heart defects have been estimated to be present in 20% of AOS patients; reported malformations include ventricular septal defects, anomalies of the great arteries and their valves, and tetralogy of Fallot (summary by Stittrich et al., 2014). For a discussion of genetic heterogeneity of Adams-Oliver syndrome, see AOS1 (100300).
Autosomal recessive SPG9B is a neurologic disorder characterized by early-onset complex spastic paraplegia. Affected individuals had delayed psychomotor development, intellectual disability, and severe motor impairment. More variable features include dysmorphic facial features, tremor, and urinary incontinence (summary by Coutelier et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Spondyloepiphyseal dysplasia with accumulation of glycoprotein in chondrocytes has been designated the 'Stanescu type.' Clinical hallmarks include progressive joint contracture with premature degenerative joint disease, particularly in the knee, hip, and finger joints. Interphalangeal joints of the hands are swollen due to osseous distention of the metaphyseal ends of the phalanges. Affected individuals may be relatively tall despite the presence of a short trunk. Radiologically, there is generalized platyspondyly with mild modification of the endplates, hypoplastic pelvis, epiphyseal flattening with metaphyseal splaying of the long bones, and enlarged phalangeal epimetaphyses of the hands. In addition, the proximal femora are characteristically broad and elongated with striking coxa valga (summary by Nishimura et al., 1998).
Au-Kline syndrome is characterized by developmental delay and hypotonia with moderate-to-severe intellectual disability, and typical facial features that include long palpebral fissures, ptosis, shallow orbits, large and deeply grooved tongue, broad nose with a wide nasal bridge, and downturned mouth. There is frequently variable autonomic dysfunction (gastrointestinal dysmotility, high pain threshold, heat intolerance, recurrent fevers, abnormal sweating). Congenital heart disease, hydronephrosis, palate abnormalities, and oligodontia are also reported in the majority of affected individuals. Additional complications can include craniosynostosis, feeding difficulty, vision issues, osteopenia, and other skeletal anomalies.
Epilepsy, hearing loss, and mental retardation syndrome is an autosomal recessive disorder characterized by severe neurologic impairment including intellectual disability, intractable epilepsy, microcephaly, abnormal muscle tone, and sensorineural hearing loss. Most affected individuals are nonambulatory, cannot sit unassisted, and have no speech development. More variable features include feeding difficulties, poor growth, cortical visual impairment, spasticity, scoliosis, immunodeficiency, and thrombocytopenia (summary by Tanaka et al., 2015).
Common variable immunodeficiency-12 is an autosomal dominant primary immunodeficiency characterized by recurrent infections, mainly respiratory, associated with hypogammaglobulinemia. The disorder shows a highly variable age at onset and highly variable disease severity, even within the same family. Some patients have features of autoimmunity (summary by Fliegauf et al., 2015). For a general description and a discussion of genetic heterogeneity of common variable immunodeficiency, see CVID1 (607594).
Noonan syndrome is an autosomal dominant disorder characterized by short stature, craniofacial dysmorphism, short and/or webbed neck, cardiac abnormalities, cryptorchidism, and coagulation defects (summary by Yamamoto et al., 2015). For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950).
Klippel-Feil syndrome-4 with nemaline myopathy and facial dysmorphism is an autosomal recessive disorder characterized mainly by severe hypotonia apparent from infancy. Klippel-Feil anomaly is primarily defined by fusion of the cervical spine, with associated low posterior hairline and limited neck mobility being observed in about half of patients (summary by Alazami et al., 2015). For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100).
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia with or without polydactyly, see SRTD1 (208500).
In patients with SSMED, short stature and microcephaly are apparent at birth, and there is progressive postnatal growth failure. Endocrine dysfunction, including hypergonadotropic hypogonadism, multinodular goiter, and diabetes mellitus, is present in affected adults. Progressive ataxia has been reported in some patients, with onset ranging from the second to fifth decade of life. In addition, a few patients have developed tumors, suggesting that there may be a predisposition to tumorigenesis. In contrast to syndromes involving defects in other components of the nonhomologous end-joining (NHEJ) complex (see, e.g., 606593), no clinically overt immunodeficiency has been observed in SSMED, although laboratory analysis has revealed lymphopenia or borderline leukopenia in some patients (Murray et al., 2015; Bee et al., 2015; de Bruin et al., 2015; Guo et al., 2015).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, and congenital muscular dystrophy. The phenotype includes the alternative clinical designation Walker-Warburg syndrome (WWS), which is associated with death in infancy. The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1), collectively known as 'dystroglycanopathies' (summary by Geis et al., 2013 and Riemersma et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Nonmedullary thyroid cancer (NMTC) comprises cancer of follicular cell origin and accounts for more than 95% of all cases of thyroid cancer. Familial NMTC accounts for 3 to 9% of all cases of thyroid cancer and has an autosomal dominant mode of inheritance. Most cases of familial NMTC are papillary thyroid cancer (PTC), which is the most common type of thyroid cancer (summary by Gara et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of NMTC, see NMTC1 (188550).
Nonmedullary thyroid cancer (NMTC) refers to neoplasms originating from the thyroid follicular cells and represents 80 to 95% of all thyroid cancers. Approximately 5% of NMTC occurs on the background of a familial predisposition. Although papillary thyroid carcinoma (PTC) is usually the most frequent thyroid lesion in NMTC families, multinodular goiter (MNG) and follicular thyroid adenoma also occur (summary by Pereira et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of NMTC, see NMTC1 (188550).
Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals also have cerebellar or pontocerebellar atrophy on brain imaging, and they may show abnormal movements, such as ataxia, dysmetria, and myoclonus. The most severely affected patients are hypotonic at birth and die in infancy (summary by Abrams et al., 2015 and Wan et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of HMSN6, see HMSN6A (601152).
Hereditary sensory and autonomic neuropathy type VIII is an autosomal recessive neurologic disorder characterized by congenital insensitivity to pain resulting in ulceration to the fingers, tongue, lips, and other distal appendages. Affected individuals may also have decreased sweating and tear production (summary by Chen et al., 2015). For a discussion of genetic heterogeneity of hereditary sensory and autonomic neuropathy, see HSAN1A (162400).
Primary ciliary dyskinesia-32 is an autosomal recessive disorder caused by defective structure and function of cilia. Ciliary dysfunction causes respiratory distress in term neonates, impaired mucociliary clearance, chronic respiratory infections, bronchiectasis, and infertility. The ciliary defect affects the central pair complex and radial spokes of the 9+2 motile cilia; affected individuals do not have situs abnormalities (summary by Jeanson et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-2 is a mitochondrial disorder characterized by adult onset of progressive external ophthalmoplegia, exercise intolerance, muscle weakness, and signs and symptoms of spinocerebellar ataxia, such as impaired gait and dysarthria. Some patients may have respiratory insufficiency. Laboratory studies are consistent with a defect in mtDNA replication (summary by Reyes et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive PEO, see PEOB1 (258450).
The Cincinnati type of acrofacial dysostosis is a ribosomopathy characterized by a spectrum of mandibulofacial dysostosis phenotypes, with or without extrafacial skeletal defects (Weaver et al., 2015).
Early infantile epileptic encephalopathy-50 is an autosomal recessive progressive neurodegenerative neurometabolic disorder characterized by delayed psychomotor development, early-onset seizures, severe developmental regression, and normocytic anemia. Onset is within the first years of life. Evidence suggests that affected children can have a favorable response to treatment with uridine (summary by Koch et al., 2017). For a discussion of genetic heterogeneity of early infantile epileptic encephalopathy, see 308350.
Spastic paraplegia-74 is an autosomal recessive neurologic disorder characterized by onset of slowly progressive lower limb spasticity, optic atrophy, and peripheral neuropathy in the first decade (summary by Lossos et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Basel-Vanagaite-Smirin-Yosef syndrome is an autosomal recessive multiple congenital anomaly disorder characterized by severely delayed psychomotor development resulting in mental retardation, as well as variable eye, brain, cardiac, and palatal abnormalities (summary by Basel-Vanagaite et al., 2015).
Frontotemporal dementia and/or amyotrophic lateral sclerosis-4 is an autosomal dominant neurodegenerative disorder characterized by adult or late adult onset of cognitive impairment, behavioral abnormalities, and speech apraxia and/or upper and lower motor neuron signs. The phenotype is highly variable (summary by Freischmidt et al., 2015). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550).
Frontotemporal dementia and/or amyotrophic lateral sclerosis-3 is an autosomal dominant neurodegenerative disorder characterized by adult or late adult onset of cognitive impairment, behavioral abnormalities, and speech apraxia and/or upper and lower motor neuron signs. Some patients may also develop Paget disease of bone. The phenotype is highly variable, even within families (summary by Rea et al., 2014). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550).
Autosomal dominant epilepsy with auditory features (ADEAF) is a focal epilepsy syndrome with auditory symptoms and/or receptive aphasia as prominent ictal manifestations. The most common auditory symptoms are simple unformed sounds including humming, buzzing, or ringing; less common forms are distortions (e.g., volume changes) or complex sounds (e.g., specific songs or voices). Ictal receptive aphasia consists of a sudden onset of inability to understand language in the absence of general confusion. Less commonly, other ictal symptoms may occur, including sensory symptoms (visual, olfactory, vertiginous, or cephalic) or motor, psychic, and autonomic symptoms. Most affected individuals have focal to bilateral tonic-clonic seizures, usually accompanied by ""focal aware"" and ""focal impaired-awareness"" seizures, with auditory symptoms as a major focal aware seizure manifestation. Some persons have seizures precipitated by sounds such as a ringing telephone. Age at onset is usually in adolescence or early adulthood (range: age 4-50 years). The clinical course of ADEAF is benign. Seizures are usually well controlled after initiation of medical therapy.
Immunodeficiency-40 is an autosomal recessive primary form of combined immunodeficiency mainly affecting T-cell number and function, with other more variable defects in B-cell and NK-cell function. Patients have onset of severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation (summary by Dobbs et al., 2015).
46,XY females with gonadal dysgenesis have streak gonads but look like normal females at birth. They do not develop secondary sexual characteristics at puberty and do not menstruate. They are chromatin-negative and are usually of normal stature, without the somatic stigmata of Turner syndrome (see 163950) (summary by Mann et al., 1983). For a discussion of genetic heterogeneity of 46,XY sex reversal, see SRXY1 (400044).
Hypomyelinating leukodystrophy-10 is an autosomal recessive neurologic disorder characterized by postnatal progressive microcephaly, severely delayed psychomotor development, and hypomyelination on brain imaging (summary by Nakayama et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080.
HOMGSMR1 is characterized by onset of seizures associated with low serum magnesium in the first year of life. Affected individuals show variable degrees of delayed psychomotor development (summary by Arjona et al., 2014). Genetic Heterogeneity of Hypomagnesemia, Seizures, and Mental Retardation HOMGSMR2 (618314) is caused by mutation in the ATP1A1 gene (182310) on chromosome 1p13.
Autoimmune interstitial lung, joint, and kidney disease is an autosomal dominant systemic autoimmune disorder characterized by interstitial lung disease, inflammatory arthritis, and immune complex-mediated renal disease. Laboratory studies show high-titer autoantibodies. Symptoms appear in the first 2 decades of life, but there is incomplete penetrance (summary by Watkin et al., 2015).
Dystonia-27 is an autosomal recessive neurologic disorder characterized by onset of segmental isolated dystonia mainly affecting the craniocervical region and upper limbs in the first 2 decades of life (summary by Zech et al., 2015).
Myoclonic dystonia-26 is an autosomal dominant neurologic disorder characterized by onset of myoclonic jerks affecting the upper limbs in the first or second decade of life. The disorder is progressive, and patients later develop dystonia with predominant involvement of the craniocervical regions and sometimes the trunk and/or lower limbs. Dystonia dominates the clinical picture (summary by Mencacci et al., 2015).
Infants with ISCA2-related mitochondrial disorder (IRMD) typically attain normal development in the first months of life. At age three to seven months, affected individuals usually present with a triad of neurodevelopmental regression, nystagmus with optic atrophy, and diffuse white matter disease. As the disease progresses, global psychomotor regression continues at a variable pace and seizures may develop. Affected children become vegetative within one to two years. During their vegetative state, which may persist for years, affected individuals are prone to recurrent chest infections that may require ventilator support. Most affected individuals die during early childhood.
White-Sutton syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and a characteristic constellation of dysmorphic facial features. Additional features may include hypotonia, sensorineural hearing impairment, visual defects, joint laxity, and gastrointestinal difficulties, such as poor feeding (summary by White et al., 2016). A significant number of patients have autism or autistic features (summary by Stessman et al., 2016).
Parkinson disease-21 (PARK21) is an autosomal dominant form of typical adult-onset Parkinson disease characterized by tremor, rigidity, bradykinesia, postural instability, and good response to levodopa treatment (summary by Vilarino-Guell et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).
PPP2R5D-related neurodevelopmental disorder is characterized by mild to severe neurodevelopmental delay. Pronounced hypotonia with delay in gross motor skills is common. Onset of independent walking varies widely and ataxia is reported. All reported individuals have speech impairment, with a wide range of abilities. Autism spectrum disorder is reported in six individuals. Macrocephaly is common. Seizures and ophthalmologic abnormalities are reported in fewer than half of individuals. Additional anomalies include skeletal, endocrine, and cardiac malformations, each reported in a few individuals. To date, 23 individuals with PPP2R5D-related neurodevelopmental disorder have been reported.
Autosomal recessive spinocerebellar ataxia-20 is a neurodevelopmental disorder characterized by severely delayed psychomotor development with poor or absent speech, wide-based or absent gait, coarse facies, and cerebellar atrophy (summary by Thomas et al., 2014).
Lissencephaly-7 with cerebellar hypoplasia is a severe neurodevelopmental disorder characterized by lack of psychomotor development, facial dysmorphism, arthrogryposis, and early-onset intractable seizures resulting in death in infancy (summary by Magen et al., 2015). For a general description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Singleton-Merten syndrome-2 is characterized by variable expression of glaucoma, aortic calcification, and skeletal abnormalities, without dental anomalies (summary by Jang et al., 2015). For a general phenotypic description and discussion of genetic heterogeneity of Singleton-Merten syndrome, see SGMRT1 (182250).
Lichtenstein-Knorr syndrome is an autosomal recessive neurologic disorder characterized by postnatal onset of severe progressive sensorineural hearing loss and progressive cerebellar ataxia. Features usually develop in childhood or young adulthood (summary by Guissart et al., 2015).
Lethal congenital contracture syndrome-8, an axoglial form of arthrogryposis multiplex congenita, is characterized by congenital distal joint contractures, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period (Laquerriere et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of lethal congenital contracture syndrome, see LCCS1 (253310).
Lethal congenital contracture syndrome-7, an axoglial form of arthrogryposis multiplex congenita (AMC), is characterized by congenital distal joint contractures, polyhydramnios, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period (Laquerriere et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of lethal congenital contracture syndrome, see LCCS1 (253310).
Mitochondrial short-chain enoyl-CoA hydratase-1 deficiency is an autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia (summary by Peters et al., 2014).
CLPB (caseinolytic peptidase B) deficiency is characterized by neurologic involvement and neutropenia, which range from severe to mild. To date, a total of 26 individuals from 16 families have been reported. In severe CLPB deficiency, death usually occurs at a few months of age as a result of significant neonatal neurologic involvement (hyperekplexia or absence of voluntary movements, hypotonia or hypertonia, swallowing problems, respiratory insufficiency, and epilepsy) and severe neutropenia associated with life-threatening infections. In moderate CLPB deficiency neurologic abnormalities in infancy are comparable to but less severe than those observed in the severe phenotype (e.g., hypotonia and feeding problems) and in later childhood can include spasticity, a progressive movement disorder (ataxia, dystonia, and/or dyskinesia), epilepsy, and intellectual disability ranging from mild learning disability to limited development of all cognitive and motor functions. Neutropenia is variable, but not life threatening. In mild CLPB deficiency there is no neurologic involvement, intellect is normal, and neutropenia is mild and intermittent. Life expectancy is normal.
Amelogenesis imperfecta type IF is characterized by hypoplastic enamel of the primary and secondary dentition. The teeth may appear rough and discolored, and the tooth enamel may be absent, pitted, or of varying thickness (Poulter et al. (2014)).
Ataxia-oculomotor apraxia-4 is an autosomal recessive neurologic disorder characterized by onset of dystonia and ataxia in the first decade. Additional features include oculomotor apraxia and peripheral neuropathy. Some patients may show cognitive impairment. The disorder is progressive, and most patients become wheelchair-bound in the second or third decade (summary by Bras et al., 2015). For a discussion of genetic heterogeneity of ataxia-oculomotor apraxia, see AOA1 (208920).
CLIFAHDD is a congenital disorder characterized by congenital contractures of the limbs and face, resulting in characteristic facial features, hypotonia, and variable degrees of developmental delay. All reported cases have occurred de novo (summary by Chong et al., 2015).
Interstitial lung and liver disease is an autosomal recessive disorder characterized by onset of respiratory insufficiency and progressive liver disease in infancy or early childhood. Pathologic examination of lung lavage is consistent with pulmonary alveolar proteinosis (summary by Hadchouel et al., 2015).
Premature ovarian failure-10 (POF10) represents a syndrome characterized by primary amenorrhea, hypergonadotropic ovarian insufficiency, and genomic instability in somatic cells. For a general phenotypic description and discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360). For a discussion of genetic heterogeneity of age at natural menopause, see MENOQ1 (300488).
Hereditary neuropathy with or without age-related macular degeneration is a complex autosomal dominant syndrome characterized by a variable peripheral neuropathy resembling demyelinating Charcot-Marie-Tooth disease (see, e.g., CMT1A, 118220) and/or axonal CMT (see, e.g., CMT2A1, 118210) with sensorimotor impairment mainly of the distal lower extremities, or spinal CMT, also known as distal hereditary motor neuropathy (see, e.g., HMN1; 182960) with intact sensation. Age-related macular degeneration, if present, shows very late onset in the seventies or eighties. In addition, some patients may show hyperelasticity of the skin or joints. The age at onset of neuropathy and severity of the disorder is highly variable, even within families (summary by Auer-Grumbach et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration, see 603075.
Nonmedullary thyroid cancer (NMTC) comprises thyroid cancers of follicular cell origin and accounts for more than 95% of all thyroid cancer cases. The remaining cancers originate from parafollicular cells (medullary thyroid cancer, MTC; 155240). NMTC is classified into 4 groups: papillary, follicular, Hurthle cell (607464), and anaplastic. Approximately 5% of NMTC is hereditary, occurring as a minor component of a familial cancer syndrome (e.g., familial adenomatous polyposis 175100, Carney complex 160980) or as a primary feature (familial NMTC or FNMTC). Papillary thyroid cancer (PTC) is the most common histologic subtype of FNMTC, accounting for approximately 85% of cases (summary by Vriens et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of NMTC, see NMTC1 (188550).
Diamond-Blackfan anemia is a disorder that primarily affects the bone marrow. People with this condition often also have physical abnormalities affecting various parts of the body.The major function of bone marrow is to produce new blood cells. In Diamond-Blackfan anemia, the bone marrow malfunctions and fails to make enough red blood cells, which carry oxygen to the body's tissues. The resulting shortage of red blood cells (anemia) usually becomes apparent during the first year of life. Symptoms of anemia include fatigue, weakness, and an abnormally pale appearance (pallor).People with Diamond-Blackfan anemia have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS), which is a disorder in which immature blood cells fail to develop normally. Individuals with Diamond-Blackfan anemia also have an increased risk of developing a bone marrow cancer known as acute myeloid leukemia (AML), a type of bone cancer called osteosarcoma, and other cancers.Approximately half of individuals with Diamond-Blackfan anemia have physical abnormalities. They may have an unusually small head size (microcephaly) and a low frontal hairline, along with distinctive facial features such as wide-set eyes (hypertelorism); droopy eyelids (ptosis); a broad, flat bridge of the nose; small, low-set ears; and a small lower jaw (micrognathia). Affected individuals may also have an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). They may have a short, webbed neck; shoulder blades that are smaller and higher than usual; and abnormalities of their hands, most commonly malformed or absent thumbs. About one-third of affected individuals have slow growth leading to short stature.Other features of Diamond-Blackfan anemia may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), or eyes that do not look in the same direction (strabismus). Affected individuals may also have kidney abnormalities; structural defects of the heart; and, in males, the opening of the urethra on the underside of the penis (hypospadias).The severity of Diamond-Blackfan anemia may vary, even within the same family. Increasingly, individuals with ""non-classical"" Diamond-Blackfan anemia have been identified. This form of the disorder typically has less severe symptoms. For example, some affected individuals have mild anemia beginning later in childhood or in adulthood, while others have some of the physical features but no bone marrow problems.
MLASA3 is a severe mitochondrial disorder with early infantile presentation of transfusion-dependent sideroblastic anemia in the setting of failure to thrive, hearing loss, epilepsy, stroke-like episodes, and severe developmental delay (summary by Burrage et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of MLASA, see MLASA1 (600462).
Female-restricted X-linked syndromic mental retardation-99 is an X-linked dominant neurodevelopmental disorder characterized by delayed psychomotor development and mild to moderate intellectual disability. Affected females can have a wide range of additional congenital anomalies, including scoliosis, postaxial polydactyly, mild cardiac or urogenital anomalies, dysmorphic facial features, and mild structural brain abnormalities (summary by Reijnders et al., 2016).
X-linked syndromic mental retardation-34 is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with poor speech, dysmorphic facial features, and mild structural brain abnormalities, including thickening of the corpus callosum (summary by Mircsof et al., 2015).
X-linked syndromic mental retardation-33 is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and characteristic facial features (summary by O'Rawe et al., 2015).
Ritscher-Schinzel syndrome-2 is an X-linked recessive syndromic form of intellectual disability associated with posterior fossa defects, cardiac malformations, and minor abnormalities of the face and distal extremities (summary by Kolanczyk et al., 2015). For a discussion of genetic heterogeneity of Ritscher-Schinzel syndrome, see RTSC1 (220210).
Reducing-body myopathy (RBM) is a rare myopathy characterized pathologically by the presence of intracytoplasmic inclusion bodies strongly stained by menadione-linked alpha-glycerophosphate dehydrogenase (MAG) in the absence of substrate, alpha-glycerophosphate. The term 'reducing body' refers to the reducing activity of the inclusions to nitroblue tetrazolium (NBT) in the absence of substrate. This condition is also commonly associated with rimmed vacuoles and cytoplasmic bodies. The clinical features of RBM are variable; a severe form has onset in infancy or early childhood and results in severe disability or early death, and a less severe form has onset in late childhood or adulthood (RBMX1B; 300718) (summary by Liewluck et al., 2007 and Shalaby et al., 2009).
Nonmedullary thyroid cancer (NMTC) comprises thyroid cancers of follicular cell origin and accounts for more than 95% of all thyroid cancer cases. The remaining cancers originate from parafollicular cells (medullary thyroid cancer, MTC; 155240). NMTC is classified into 4 groups: papillary, follicular, Hurthle cell (607464), and anaplastic. Approximately 5% of NMTC is hereditary, occurring as a minor component of a familial cancer syndrome (e.g., familial adenomatous polyposis, 175100, Carney complex, 160980) or as a primary feature (familial NMTC or FNMTC). Papillary thyroid cancer (PTC) is the most common histologic subtype of FNMTC, accounting for approximately 85% of cases (summary by Vriens et al., 2009). Follicular thyroid cancer (FTC) accounts for approximately 15% of NMTC and is defined by invasive features that result in infiltration of blood vessels and/or full penetration of the tumor capsule, in the absence of the nuclear alterations that characterize papillary carcinoma. FTC is rarely multifocal and usually does not metastasize to the regional lymph nodes but tends to spread via the bloodstream to the lung and bones. An important histologic variant of FTC is the oncocytic (Hurthle cell, oxyphilic) follicular carcinoma composed of eosinophilic cells replete with mitochondria (summary by Bonora et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of NMTC, see NMTC1 (188550).
Singleton-Merten syndrome (SGMRT) is an uncommon autosomal dominant disorder characterized by abnormalities of blood vessels, teeth, and bone. Calcifications of the aorta and aortic and mitral valves occur in childhood or puberty and can lead to early death. Dental findings include delayed primary tooth exfoliation and permanent tooth eruption, truncated tooth root formation, early-onset periodontal disease, and severe root and alveolar bone resorption associated with dysregulated mineralization, leading to tooth loss. Osseous features consist of osteoporosis, either generalized or limited to distal extremities, distal limb osteolysis, widened medullary cavities, and easy tearing of tendons from bone. Less common features are mild facial dysmorphism (high anterior hair line, broad forehead, smooth philtrum, thin upper vermilion border), generalized muscle weakness, psoriasis, early-onset glaucoma, and recurrent infections. The disorder manifests with variable inter- and intrafamilial phenotypes (summary by Rutsch et al., 2015). Genetic Heterogeneity of Singleton-Merten Syndrome An atypical form of Singleton-Merten syndrome (SGMRT2; 616298) is caused by mutation in the DDX58 gene (609631) on chromosome 9p21.
Sideroblastic anemia comprises a heterogeneous group of inherited and acquired disorders characterized by ineffective erythropoiesis. Anemia, if present, may be microcytic or macrocytic. Sometimes a dimorphic picture is observed in which 2 populations of erythrocytes can be detected in peripheral blood smears. The presence of ringed sideroblasts (erythroblasts containing pathologic mitochondrial iron deposits) in bone marrow is pathognomonic for sideroblastic anemia (van Waveren Hogervorst et al., 1987; Schmitz-Abe et al., 2015). For a discussion of genetic heterogeneity of sideroblastic anemia, see SIDBA1 (300751).
A form of Ehlers-Danlos syndrome that affects the soft connective tissue and is characterised by skin hyperextensibility, widened atrophic scars and joint hypermobility.
The 10q22.3-q23.2 region is characterized by a complex set of low-copy repeats (LCRs), which can give rise to various genomic changes mediated by nonallelic homologous recombination (NAHR). Recurrent deletions of chromosome 10q22.3-q23.2, including the BMPR1A gene (601299) have been associated with dysmorphic facies, developmental delay, and multiple congenital anomalies. Some patients with deletions that extend distally to include the PTEN gene (601728) have a more severe phenotype with infantile/juvenile polyposis, macrocephaly, dysmorphic facial features, and developmental delay (summary by van Bon et al., 2011).
VATER is a mnemonically useful acronym for the nonrandom association of vertebral defects (V), anal atresia (A), tracheoesophageal fistula with esophageal atresia (TE), and radial or renal dysplasia (R). This combination of associated defects was pointed out by Quan and Smith (1972). Nearly all cases have been sporadic. VACTERL is an acronym for an expanded definition of the association that includes cardiac malformations (C) and limb anomalies (L). The VACTERL association is a spectrum of various combinations of its 6 components, which can be a manifestation of several recognized disorders rather than a distinct anatomic or etiologic entity (Khoury et al., 1983). Also see VATER/VACTERL association with hydrocephalus (VACTERL-H; 276950) and VACTERL with or without hydrocephalus (VACTERLX; 314390).
An abnormal increase in the volume of cardiac myocytes.
Failure of oocytes to proceed through the stages of meiosis with stoppage at the first metaphase stage.
Swelling of the hand at the knuckles, that gives the fingers a spindle shape (i.e., a round stick with tapered end and a broader base).
The development of two or more cartilage capped bony outgrowths of the long bones.Develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. The number may vary significantly within and between families. The majority are asymptomatic and located in bones that develop from cartilage, especially the long bones of the extremities, predominantly around the knee. The most important complication is malignant transformation towards secondary peripheral chondrosarcoma. Germline mutations in EXT1 or EXT2, are found in almost 90% of patients. An autosomal dominant disorder.
A myocardial infarction that does not produce elevations in the ST segments of the ELECTROCARDIOGRAM. ST segment elevation of the ECG is often used in determining the treatment protocol (see also ST Elevation Myocardial Infarction).
A developmental disorder of the eye with manifestation of unilateral or bilateral microphthalmia associated with ocular coloboma.
A genetic disorder with characteristics of the appearance of numerous cysts spread throughout the liver. Women are predominantly affected and have a larger number of cysts than affected males. Cysts are undetectable early in life and usually appear after the age of 40 years. Their number and size increases with age. Symptoms depend on the mass (compression effect) some patients are asymptomatic. Liver function is usually normal. There is no portal hypertension. Extrahepatic manifestations are very rare and may include intracranial aneurysms (usually small sized and at a low risk of rupture) and mitral leaflet abnormalities. Liver cysts result from overgrowth of biliary epithelium or from dilatation of peribiliary glands. Some cases occur sporadically, but most are inherited as an autosomal dominant trait.
Impairment of the vestibular function of both inner ears which can cause difficulties with balance, gait, VERTIGO, and visual blurring.
A congenital malformation of the tricuspid valve characterized by leaflet deformation.
Thrombomodulin is a cofactor in the thrombin induced activation of Protein C. In the case of deficiency there will be less Protein C and tendency to clot
A rare variant of lichen planopilaris with characteristic of symmetrical progressive band-like anterior hair loss of the scalp. Prevalence is unknown. It most commonly affects postmenopausal women, although it has also been reported in men and premenopausal women. Progressive recession of the frontal and temporal hairline is observed. Approximately half of all cases also have eyebrow loss; less often there is hair loss in other parts of the body. It is only very rarely associated with classic lichen planus lesions elsewhere. It is suggested that the disease could have a hormonal origin, but to date the precise cause remains unknown.
Defined by the presence of pancreatic cancer in two or more first-degree relatives. In familial cases, disease onset occurs before 50 years of age, earlier than for the other forms of pancreatic cancer. Prognosis is poor.
The quantitative measurement of the effective regurgitant orifice area of a cardiac valve.
Includes diffuse and signet-ring cell carcinoma and other variants
A response indicating that an individual is or has been mostly dissatisfied.
A response indicating that something happens or happened about half of the time.
A response indicating that something happens or happened less than one in five times.
Acute separation of the periodontal tissue from the root by 1-2 millimeters of clinical attachment loss in less than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Acute separation of the periodontal tissue from the root by 3-4 millimeters of clinical attachment loss in less than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Acute separation of the periodontal tissue from the root by 5 millimeters or more of clinical attachment loss in less than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Acute separation of the periodontal tissue from the root by 3-4 millimeters of clinical attachment loss in greater than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Acute separation of the periodontal tissue from the root by 5 millimeters or more of clinical attachment loss in greater than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Chronic separation of the periodontal tissue from the root by 1-2 millimeters of clinical attachment loss in less than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Chronic separation of the periodontal tissue from the root by 3-4 millimeters of clinical attachment loss in less than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Chronic separation of the periodontal tissue from the root by 5 millimeters or more of clinical attachment loss in less than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Chronic separation of the periodontal tissue from the root by 1-2 millimeters of clinical attachment loss in greater than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Chronic separation of the periodontal tissue from the root by 3-4 millimeters of clinical attachment loss in greater than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Chronic separation of the periodontal tissue from the root by 5 millimeters or more of clinical attachment loss in greater than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
Acute separation of the periodontal tissue from the root by 1-2 millimeters of clinical attachment loss in greater than 30% of sites as measured from the cementoenamel junction to the base of the probable pocket (gingival sulcus).
A rare autosomal anomaly due to the presence of an extra copy of chromosome 4 in a fraction of all cells with a variable phenotype. Typical characteristics are intrauterine growth retardation, low birth weight/length/head circumference, mild intellectual deficit, congenital heart defects, hypertrophic cardiomyopathy, dysmorphic features (asymmetry of the face, eyebrow anomalies, low-set, posterior rotated, dysplastic ears, micro-/retrognathia), characteristic thumb abnormalities (aplasia, hypoplasia) and skin abnormalities (hypo/hyperpigmentation). Delayed puberty may be associated.
An autosomal recessive form of osteopetrosis caused by mutation(s) in at least 8 genes related to osteoclast function. This condition is characterized by the failure of osteoclasts to resorb bone, resulting in impaired bone modeling/remodeling, and skeletal fragility despite increased bone mass; it is also associated with hematopoietic insufficiency, hypocalcemia, disturbed tooth eruption, nerve entrapment syndromes, and growth impairment. Some cases are also associated with progressive neurological deterioration.
An autosomal dominant form of osteopetrosis due to mutation(s) in the CLCN7 gene, encoding H(+)/Cl(-) exchange transporter 7. Clinical features include sclerosis involving the spine, the pelvis, and the base of the skull. Complications can include optic nerve compression, dental abscesses, anemia, and bone fragility. One third of individuals who carry a CLCN7 mutation have a normal skeletal phenotype.
A rare genetic multiple congenital anomalies syndrome with characteristics of second branchial arch anomalies (branchial cysts and fistulae), malformations of the outer, middle and inner ear associated with sensorineural, mixed or conductive hearing loss and the absence of renal abnormalities. Typical ear findings consist of malformed auricles (lop or cupped ears), preauricular pits and/or tags, and middle and/or inner ear dysplasias (including cochlear, vestibular and semicircular channel hypoplasia, malformation of the ossicles and of middle ear space).
Reintubation of a patient due to acute respiratory failure following extubation.
The clinical situation in which a conventionally trained anaesthesiologist experiences difficulty with mask ventilation, difficulty with tracheal intubation or both.
The occurrence of abnormal involuntary movements that are incongruent with a known neurologic cause and are significantly improved on neurological exam with distraction or non-physiologic maneuvers. The disorder is defined by its clinical appearance, rather than by any causative speculation.
A primary immunodeficiency with characteristics of increased susceptibility to pyogenic bacterial infections, including invasive pneumococcal, invasive staphylococcal and pseudomonas disease. Only 24 cases have been reported. The disease presents in childhood with recurrent, life-threatening, pyogenic bacterial infections. This predisposition to life-threatening infections seems transient and lasts during the first 10 years of life in the cases reported so far. Myeloid differentiation primary response 88 (MyD88) deficiency results from mutations in the MYD88 gene (3p22-3p21.3) which generally abolishes the cytokine responses of the blood cells. Transmission is autosomal recessive.
A genetic variant of Mendelian susceptibility to mycobacterial diseases with characteristics of a complete deficiency in interferon gamma receptor 1(IFN-gammaR1), leading to impaired IFN-gamma immunity and, consequently, to severe and often fatal infections with bacillus Calmette-Guérin and other environmental mycobacteria. Infection is disseminated and can involve soft tissue, bone marrow, lungs, skin, bones and lymph nodes. Manifestations include fever, weight loss, hepatosplenomegaly, lymphadenopathies and lepromatous-like lesions. Caused by complete IFN-gammaR1 deficiency due to mutations in the IFNGR1 gene on chromosome 6q23-q24. Transmission is autosomal recessive.
A chromosomal anomaly with characteristics of developmental and language delays, mild intellectual disability, social impairments (autism spectrum disorders), mild variable dysmorphism and predisposition to obesity. The proximal 16p11.2 microdeletion syndrome most commonly refers to a distinct deletion of approximately 593 kb at chromosomal coordinates 29.5-30.1 Mb comprising 24 genes. The relationship between genotype and clinical phenotype remains elusive.
A variant of lichen planopilaris characterised by the clinical triad of progressive cicatricial (scarring) alopecia of the scalp, follicular keratotic papules on glabrous skin, and variable alopecia of the axillae and groin. It is a very rare disease but the exact prevalence is not known. It mainly affects women during adulthood (30-60 years of age). Scarring alopecia presents as small confluent patches that are atrophic and cicatricial in the centre but erythematous and squamous around the edges. Follicular keratosis presents as pruritic, red-brown, follicular spiny papules on the trunk and extremities. Generally, the three clinical features appear simultaneously but in some cases, scalp alopecia precedes the follicular keratosis. Aetiology is unknown.
A demyelinating polyneuropathy characterised clinically by sensory ataxia, tremor, paraesthesia, and impaired gait.
Characterised by early neonatal onset of hypotonia, hypertrophic cardiomyopathy and apnoeic spells within hours after birth accompanied by lactic acidosis, hyperammonaemia and 3-methylglutaconic aciduria. Most patients who survive the neonatal period have mild cranio-facial dysmorphism with low set ears, prominent nasal bridge and retrognathia, persisting muscular hypotonia and moderate psychomotor developmental delay. The result of an isolated decrease in the tissue content and activity of mitochondrial FoF1 ATP synthase caused by depressed biosynthesis of the enzyme. This enzyme defect is present in all tissues and is due to autosomal recessive mutations in the TMEM70 gene (8q21.11), encoding ancillary factor of ATP synthase biogenesis.
A rare lymphoma of the lung defined as a clonal lymphoid proliferation affecting one or both lungs in a patient with no detectable extrapulmonary involvement at diagnosis or during the subsequent 3 months. Comprises low grade/indolent B cell forms, the most frequent form represented by the marginal B-cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) and other non-MALT low grade lymphomas; and more rarely high-grade B-cell and lymphomatoid granulomatosis. Very rare and represents only 3-4% of extranodal non-Hodgkin lymphoma.
A form of beta-thalassaemia characterised by splenomegaly and petechiae, moderate thrombocytopenia, prolonged bleeding time due to platelet dysfunction, reticulocytosis and mild beta-thalassaemia. Prevalence of this form is not known. The disorder is not associated with mutations in the HBB gene (11p15.5), but with mutations in the gene encoding GATA-binding protein-1 (GATA1; Xp11.23) that result in reduced expression of the beta-globin genes. Transmission is X-linked.
A familial form of essential thrombocythaemia, a myeloproliferative disorder characterised by a sustained elevation of platelet number with a tendency for thrombosis and haemorrhage. Patients commonly manifest microcirculatory disturbances or vaso-motor events. The disease is less frequently associated with an increased risk of haemorrhage, mild splenomegaly, and progression towards myelofibrosis with myeloid metaplasia or transformation to leukaemia. The genetic cause of the inherited predisposition is not known. Transmission appears to be autosomal dominant with incomplete penetrance.
A permanent thyroid deficiency that is present from birth, characterised by low levels of thyroid hormones caused by disorders in the development or function of the pituitary. The clinical manifestations can be subtle, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. Goitre is always absent. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment hypothyroidism results in severe intellectual deficit and short stature. The hypothyroidism is caused by mutations in genes regulating pituitary gland development including HESX1, LHX3, LHX4, POU1F1 and PROP1 (3p21.2-p21.1, 9q34.3, 1q25, 3p11 and 5q).
A permanent thyroid hormone deficiency that is present from birth. The majority of cases are asymptomatic but some may have features of hypothyroidism including decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanelles (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. In 90% of cases the peripheral resistance to thyroid hormones is caused by dominantly inherited mutations in genes encoding for thyroid hormone receptor beta.
A rare cause of glomerulonephritis characterised by glomerular accumulation of non-amyloid fibrils in the mesangium and the glomerular (and rarely tubular) basement membrane, and mainly presenting with renal insufficiency, micro-haematuria and nephritic range proteinuria. Aetiology is unknown. The disease is generally considered idiopathic but it may be associated with secondary causes such as monoclonal or oligoclonal gammopathy, hepatitis B and C infections, autoimmune diseases and malignancies.
A rare chromosomal anomaly with clinical manifestations of mild to severe intellectual deficit, severe developmental delay, hypotonia with tendency to develop progressive hypertonia over time, minor facial anomalies and agenesis of the corpus callosum. Thirty to fifty percent of individuals have autism. An inverted duplication with a terminal deletion of the short arm of chromosome 8 mostly occurs as either an inverted duplication from centromere to D8S552 with a pter deletion from D8S349 or as an inverted duplication from 8p11.2 or 8p21 to D8S552, with a telomeric deletion from D8349. The input of the 8p deletion to the clinical picture appears less significant than the 8p inversion duplication rearrangement. To date, all invdupdel(8p) have occurred de novo.
Autosomal recessive limb-girdle muscular dystrophy type 2I (LGMD2I) is a form of limb-girdle muscular dystrophy with characteristics of proximal limb girdle weakness predominant in the legs together with bilateral moderate scapulae winging, abdominal muscle weakness, waddling gait, calf hypertrophy, cardiomyopathy and respiratory insufficiency.
Autosomal recessive limb-girdle muscular dystrophy type 2B (LGMD2B) is a limb-girdle muscular dystrophy with characteristics of limb-girdle weakness and atrophy mostly in the shoulder pelvic girdle. Cardiac and respiratory muscles are not involved.
Autosomal dominant limb-girdle muscular dystrophy type 1B (LGMD1B) is a laminopathy with characteristics of progressive limb girdle weakness, usually affecting the pelvic girdle before humeral muscles, mild joint contractures and age-related atrioventricular cardiac conduction disturbances. Dilated cardiomyopathy is frequently associated.
Autosomal recessive limb-girdle muscular dystrophy type 2F (LGMD2F) is a limb-girdle muscular dystrophy with manifestations of limb-girdle weakness, cardiomyopathy and respiratory impairment. LGMD2F is caused by a deficit of a sarcoglycan protein and therefore belongs to a group of disorders named sarcoglycanopathy.
Autosomal recessive limb girdle muscular dystrophy type 2C (LGMD2C) is a limb girdle muscular dystrophy with manifestations of limb-girdle weakness, calf hypertrophy, diaphragmatic weakness and variable cardiac abnormalities. Ambulation may be lost by the age 12.
Nephrotic syndrome with often-early onset defined by severe proteinuria with low serum albumin and possible edema. This disease is rare but severe as it usually progresses to end-stage renal failure. Mutations in the NPHS2 gene (chromosome 1q25-q31 and encoding podocine) have been found to be involved in autosomal recessive forms of the disease. Mutations in the podocine gene have also been detected in later-onset forms and in apparently sporadic forms. Mutations in the ACTN4 gene, coding for alpha-actinine 4, have been reported in autosomal dominant forms. Familial forms of idiopathic steroid-resistant nephrotic syndrome do not respond to any treatment with steroids or immunosuppressive drugs and the disease progress to terminal renal failure.
A rare entity usually diagnosed by echocardiography. It may be limited to one of the four valves but can also involve the two atrioventricular valves and the two semilunar valves. May be the hallmark of genetic anomalies. Chromosomal anomalies should be searched when polyvalvular dysplasia is found in a fetus, namely trisomy 18 and trisomy 13. Triscuspid valve dysplasia can be the only cardiac finding in trisomy 21 and a karyotype analysis should be performed in all fetuses exhibiting this anomaly. In the absence of chromosomal anomalies, polyvalvular dysplasia can be observed in Noonan syndrome. Thickening of the different cardiac valves can be observed in various storage diseases such as mucopolysaccharidoses. In these later conditions, it develops after the neonatal period and is frequently associated with extracardiac symptoms suggestive of the diagnosis.
A very rare mitochondrial disease with clinical characteristic of cardioencephalomyopathy resulting in death in infancy.
A form of severe combined immunodeficiency with severe and recurrent infections, associated with diarrhea and failure to thrive. The disease is characterized by a lack of circulating T and NK (Natural Killer) cells and normal number of B lymphocytes. Results from a defect in the JAK3 gene encoding an intracellular tyrosine kinase, the Janus activating kinase 3 required for cytokine-mediated signalling. Transmission is autosomal recessive.
Congenital multiple pituitary hormone deficiency including somatotroph, thyrotroph, lactotroph, corticotroph or gonadotroph deficiencies, due to mutations of pituitary transcription factors involved in pituitary ontogenesis. Rare when compared with the high incidence of hypopituitarism induced by pituitary adenomas, transsphenoidal surgery or radiotherapy. Clinical presentation is variable, depending on the type and severity of deficiencies and on the age at diagnosis. If untreated, main symptoms include short stature, cognitive alterations or delayed puberty. Due to mutations of several genes encoding pituitary transcription factors. A diagnosis must be suspected when evident causes of hypopituitarism have been ruled out. Type of transmission varies with the factor and the mutation involved.
A type of primary congenital hypothyroidism a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis. Clinical manifestations are those of other forms of congenital hypothyroidism. In addition to features of hypothyroidism, patients can present with goiter. Caused by hereditary defects in the steps of thyroid hormone synthesis and secretion, the majority of which are transmitted in an autosomal recessive manner but at least one condition has autosomal dominant inheritance.
A patient under general anaesthesia with muscle relaxation who cannot be intubated by direct laryngoscopy and in whom mask ventilation is difficult and impossible.
A rare disorder with characteristics of sclerosis of the intrahepatic portal veins, non-cirrhotic portal hypertension, asymptomatic splenomegaly and recurrent variceal bleeding. Most commonly, the condition is detected in investigating a fortuitous finding of hypersplenism or splenomegaly. Main histopathologic findings are periportal fibrosis, occlusion of small portal veins, sclerosis of the portal venous system, and proliferation of small vascular channels within/around portal tracts. The disease is slowly progressive. Exposure to toxic substances or drugs, autoimmune and connective tissue diseases, systemic or intraabdominal infections, and clotting abnormalities have been incriminated. A genetic background has been suggested.
Dental implant which has never achieved osseointegration.
A form of autosomal dominant optic atrophy with characteristics of progressive and isolated visual loss in the first decade of life, decreased reflexes in the lower limbs and a mild cerebellar stance.
The presence in both breasts of multiple voluminous fibroadenomas with heterogeneous echo patterns. Prevalence is unknown. Mammary polyadenomatosis is a benign mastopathy caused by predominantly epithelial cell hyperplasia. Onset usually occurs during adolescence or in young women between 15 and 30 years of age.
Fetal iodine syndrome is a group of symptoms that may be observed in a fetus or newborn when the mother was exposed during pregnancy to inappropriate (excessive or insufficient) amounts of iodine, a nonmetallic halogen element. Maternal iodine can be readily transferred to the fetus, and chronic maternal exposure to iodine can lead to hypothyroidism and goiter in the offspring. The majority of the reported fatalities caused by iodine intoxication resulted from the use of iodine-containing expectorants during pregnancy. Based on these observations, the repeated or routine use of iodine-containing products is not recommended during pregnancy. In addition to the problems associated with iodine intoxication, iodine deficiency during pregnancy may be severe enough to produce hypothyroidism in the fetus.
A chromosomal anomaly characterised by an intellectual deficiency, progressive microcephaly, seizures, growth delay, distinct facial dysmorphic features and various midline defects including cardiac, corpus callosum, gastro-oesophageal and urogenital anomalies.
An idiopathic condition in which the bladder and bladder outlet are normal but the ureter is dilated to some extent. It may be obstructed, refluxing or unobstructed and not refluxing. Prevalence is unknown, but is the second most common cause of neonatal hydronephrosis. About half of cases are asymptomatic and are discovered on routine antenatal ultrasound. The cause is unknown but it may be due to high fetal urine outflow, changes in the ureter pre and postnatal or transient anatomical obstructions that improve with postnatal development, such as ureteral folds. Not known to be hereditary, but families with more than one affected member have been described.
Congenital plasminogen activator inhibitor type 1 (PAI-1) deficiency is a rare genetic bleeding disorder characterised by premature lysis of haemostatic clots and a moderate bleeding tendency. Both partial and total PAI-1 deficiencies are extremely rare disorders. PAI-1 is the physiological inhibitor of tissue-type plasminogen activator (t-PA), the main source of intravascular fibrinolysis. Affected patients carry one (heterozygote) or two (homozygote) alleles with a mutation in the SERPINE1 gene (7q22.1), resulting in partial or total antigenic PAI-1 deficiency. Transmitted as autosomal recessive traits.
Syndromic orbital border hypoplasia is a rare disorder observed in two families to date with characteristics of agenesis of the orbital margin, varying defects of the lacrimal passages, hypoplasia of the palpebral skin and tarsal plates and atresia of the nasolacrimal duct.
Idiopathic congenital hypothyroidism is a type of primary congenital hypothyroidism whose cause and prevalence are unknown. Clinical manifestations are those of other forms of congenital hypothyroidism. Goiter is always absent. Ultrasound examination and thyroid scintigraphy show a thyroid gland of normal shape and size in the normal, eutopic location. Idiopathic congenital hypothyroidism can be diagnosed after exclusion of the known causes of congenital hypothyroidism.
A type of transient congenital hypothyroidism a thyroid hormone deficiency that is not permanent. Patients may present with symptoms similar to those of permanent congenital hypothyroidism or they may be asymptomatic. It is caused by the transfer of maternal thyroid stimulating hormone (TSH) blocking antibodies, which can block the TSH receptor in the neonatal thyroid resulting in hypothyroidism in the infant. The effect can last up to 3-6 months after birth as maternal antibody levels fall. Treatment with l-thyroxine is usually required during this period.
A very rare neonatal epileptic encephalopathy disorder with clinical characteristics of myoclonic and clonic, or clonic seizures associated with apnea occurring several hours to 5 days after birth and responding to folinic acid.
Melanocortin 4 receptor (MC4R) deficiency is the commonest form of monogenic obesity identified so far. MC4R deficiency is characterised by severe obesity, an increase in lean body mass and bone mineral density, increased linear growth in early childhood, hyperphagia beginning in the first year of life and severe hyperinsulinaemia, in the presence of preserved reproductive function. MC4R is a G protein-coupled receptor involved in the hypothalamic leptin-melanocortin signalling pathway. Activation of the MC4R plays a key role in the maintenance of energy homeostasis and is associated with suppression of food intake.
This syndrome has characteristics of adult-onset severe sensory ataxic neuropathy, dysarthria and chronic progressive external ophthalmoplegia. The prevalence is unknown. Other common features include progressive gait unsteadiness, absent deep tendon reflexes, the presence of Romberg's sign, a decreased sense of vibration and proprioception and detection of red ragged fibres on muscle biopsy. The syndrome is associated with mitochondrial DNA mutations in either the POLG1 or TWINKLE genes.
A renal tubulopathy characterised by renal tubular resistance to aldosterone, characterised by hyponatraemia, metabolic acidosis and hyperkalaemia and manifesting as dehydration, secondary to urinary tract malformation and infections in infants.
Deficient lacrimation ranging from a complete absence of tears to hyposecretion of tears that is present from birth. Prevalence is unknown. Transmission is usually autosomal recessive, but dominant transmission has also been described. Artificial tears are the first treatment option, needed to avoid corneal sequelae.
The most common form of congenital adrenal hyperplasia, divided into 2 clinical groups simple virilising or salt wasting forms. Manifests with genital ambiguity in females and with adrenal insufficiency in both sexes. Girls present with ambiguous genitalia and the extent of virilisation can vary from a nearly male appearance to minimal clitoromegaly. A normal uterus and various degrees of abnormal vaginal development are seen. The external genitalia in boys are normal. The disease is caused by a mutation in the CYP21A2 gene located on chromosome 6p21.3. Follows an autosomal recessive pattern of inheritance.
One of the most severe forms of congenital adrenal hyperplasia, it is extremely rare. Congenital anomalies are typically seen in the perinatal period. Boys are not virilised and demonstrate a complete girl phenotype. The external genitalia of girls are normal. Hypoglycaemic seizures, vomiting or symptoms of dehydration are common manifestations. This disease is due to a mutation in the STAR gene, which encodes for a protein that regulates steroid hormone synthesis. The disease follows an autosomal recessive pattern of inheritance.
Papular mucinosis of infancy is a rare paediatric non progressive form of localised lichen myxoedematosus characterised by the development of firm opalescent mucinous papules on the upper arms and the trunk.
Discrete papular lichen myxedematosus is a rare chronic, slowly progressive form of localized lichen myxedematosus characterized by the development of a few to multiple small symmetrical skin-colored mucinous papules on the limbs and trunk.
A rare form of localised lichen myxoedematosus characterised by the development of skin-coloured mucinous nodules on the limbs and trunk, with mild or absent papular eruption.
An acquired from of intestinal lymphangiectasia manifesting as a protein-losing enteropathy due to another disorder such as Crohn's disease, congestive heart failure, sarcoidosis, Turner syndrome and often in patients who have undergone a Fontan operation. It is characterised by malabsorption, diarrhoea, oedema due hypoproteinaemia, steatorrhoea and serosal effusions.
An inherited, mild, non-haemolytic subtype of hereditary stomatocytosis that is associated with a temperature-dependent anomaly in red cell membrane permeability to potassium that leads to high in vitro potassium levels in samples stored below 37°C. Not associated with additional haematological abnormalities, although affected individuals may show some mild abnormalities like macrocytosis. All families identified so far have mutations in the ABCB6 gene (2q36), leading to an inherited abnormality in the movement of ions across the red cell membrane, such that when the red cells are cooled they lose potassium into the plasma. Inherited as an autosomal dominant trait. The prognosis is excellent most patients remain asymptomatic.
The presence of diffuse palmoplantar keratoderma without associated symptoms. The syndrome has been described in multiple families from the northernmost county of Sweden (Norrbotten). The palmoplantar keratoderma found in the Gamborg-Nielsen type disease is milder than that found in Mal de Meleda but more severe than that found in Thost-Unna palmoplantar keratoderma. Transmission is autosomal recessive.
An inherited epileptic syndrome characterised by cortical hand tremors, myoclonic jerks and occasional generalised or focal seizures with a non-progressive or very slowly progressive disease course, and no signs of early dementia or cerebellar ataxia. Usually presents in the second decade of life with a minor cortical hand tremor. Mapped to at least 4 different chromosomal loci. Transmitted autosomal dominantly and penetrance is high
An extremely rare skin disease described in only four families to date and characterised in males by diffuse reticulate brown hyperpigmented skin lesions developing in early childhood and a variety of systemic manifestations (recurrent pneumonia, corneal opacification, gastrointestinal inflammation, urethral stricture, failure to thrive, hypohidrosis, digital clubbing, and unruly hair and flared eyebrows), while in females, there is only cutaneous involvement with the development in early childhood of localised brown hyperpigmented skin lesions following the lines of Blaschko. This disease was first considered as a cutaneous amyloidosis, but amyloid deposits are an inconstant feature.
This syndrome is characterised by epilepsy, learning difficulties, macrocephaly, and aggressive behaviour. It has been described in males from a four-generation kindred. It is transmitted as an X-linked recessive trait and is likely to be caused by mutations in the gene encoding synapsin I (Xp11.3-q12).
This syndrome has characteristics of microphthalmia, ankyloblepharon and intellectual deficit. It has been described in seven male patients from two generations of a Northern Ireland family. It is transmitted as an X-linked recessive trait and the causative gene is localised to the Xq27-q28 region.
Syndrome with the association of arthropathy of interphalangeal, metacarpophalangeal and metatarsophalangeal joints with brachydactyly of the middle and distal phalanges. It has been described in numerous members from five generations of one large family. Inheritance is autosomal dominant.
A heterogeneous entity. Its prevalence in the general population is unknown. Nephrotic syndrome has manifestations of marked proteinuria, with reduced plasmatic levels of albumin, and potentially with edema. Familial forms are in most cases related to podocyte protein structural anomalies. Other forms result from a totally different mechanism, which has not yet been elucidated. One of the proposed hypotheses suggests that cells from the immune system could produce one or several circulating factors, which would increase the glomerular permeability to proteins. In some cases, immunosuppressive drugs, in particular cyclosporin, can prove beneficial. However, the progression to end-stage renal failure is frequent. In this case, there is a risk of nephrotic syndrome recurrence after kidney transplant.
This syndrome consists of the association of congenital nephronophthisis leading to renal failure, and hepatic fibrosis. It has been described in five members of one family, two of whom died from renal failure. The association of Boichis syndrome with tapetoretinal degeneration and intellectual deficit has also been reported in one family: the so-called Senior-Boichis syndrome could be in fact the same entity, and was later reported in a 12 year-old child.
A form of diazoxide-sensitive diffuse hyperinsulinism caused by a lowered threshold for insulin release. Characterised by excessive/uncontrolled insulin secretion and recurrent episodes of profound hypoglycaemia induced by fasting and protein rich meals, requiring rapid and intensive treatment to prevent neurological sequelae. Activating mutations of GCK (7p15.3-p15.1) that encodes glucokinase have been identified as the cause.
The association of biliary atresia and splenic abnormalities. Cardiac defect, situs inversus and a preduodenal portal vein can also be present. It represents the embryonal or syndromic form of biliary atresia. It affects newborns or infants and is characterised by jaundice, pale stools, dark urine, failure to thrive, hepatomegaly, coagulopathy, anaemia and often palpable spleen.
Disorder with clinical characteristics of low birth weight, failure to thrive, transient intrahepatic cholestasis, multiple aminoacidaemia, galactosaemia, hypoproteinaemia, hepatomegaly, decreased coagulation factors, haemolytic anaemia, variable but mostly mild liver dysfunction and hypoglycaemia.
A rare neurological mitochondrial DNA-related disorder characterised clinically by progressive paediatric-onset dystonia with variable degrees of severity.
Describes a spectrum of phenotypes with manifestations similar but milder than those seen in GRACILE syndrome and that can be associated with encephalopathy and psychiatric disorders. The prevalence is unknown, several cases have been described, presentation is variable. Most of the characteristics of GRACILE syndrome are present but they are often less severe. Signs of disturbances in iron metabolism have been described. Most infants die during the neonatal period. In those who survive, encephalopathy and psychiatric disorders have been described. This disease is due to different mutations in the BCS1L gene (2q35) encoding a protein essential in the assembly of complex III in the mitochondrial respiratory chain. Inherited autosomal recessively.
A non-syndromic, microcytic/hypochromic sideroblastic anaemia, present from early infancy and characterised by severe microcytic anaemia, which is not pyridoxine responsive, and increased serum ferritin. To date, fewer than 30 unrelated genetically characterised individuals have been reported. Clinical features are those of anaemia and iron overload and include pallor, fatigue, weakness, breathlessness, splenomegaly, hyperglycaemia, glucose intolerance and skin hyperpigmentation. Patients need blood transfusions to survive and do not respond to treatment with pyridoxine. Caused by a homozygous or compound heterozygous mutation in the SLC25A38 gene located on chromosome 3p22.1. The SLC25A38 gene mutation is transmitted as an autosomal recessive trait.
A form of diazoxide-sensitive diffuse hyperinsulinism characterised by macrosomia, transient or persistent hyperinsulinaemic hypoglycaemia, responsiveness to diazoxide and a propensity to develop maturity-onset diabetes of the young subtype 1. The disease frequently presents as neonatal hypoglycaemia. All patients are responsive to medical management with diazoxide. Family history of diabetes is usually, but not always present. Caused by mutations in HNF4A gene (20q13.12). The transmission is autosomal dominant with variable penetrance.
Anomaly of bile acid synthesis with manifestation of fat malabsorption, neonatal cholestasis and growth failure. Prevalence is unknown. Only 8 cases have been reported. Patients present with a history of neonatal cholestasis, fat and fat-soluble vitamin malabsorption and growth failure. Several mutations in the bile acid-CoA ligase gene have been found in most patients with this defect. The mode of transmission of these mutations is not known.
A form of diazoxide-sensitive diffuse hyperinsulinism characterised by hypoglycaemic episodes that are usually mild, escaping detection during infancy and usually a good clinical response to diazoxide. Autosomal dominant hyperinsulinism due to SUR1 deficiency usually has a milder phenotype when compared to that resulting from recessive K-ATP mutations.
A form of diazoxide-sensitive diffuse hyperinsulinism characterised by hypoglycaemic episodes that are usually mild, escaping detection during infancy, and usually a good clinical response to diazoxide, (but some are diazoxide resistant). Usually has a milder phenotype when compared to that resulting from recessive K+ channel mutations.
Caused by abnormal insulin production by b-cells in the pancreas that can be diffuse or focal and is characterised by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycaemia), recurrent episodes of profound hypoglycaemia and resistance to medical management with diazoxide.
A life-threatening syndrome with manifestation of progressive and painful skin ulcerations associated with calcification of medium-size and small cutaneous arterial vessels. It affects mainly patients on dialysis or after renal transplantation.
An autosomal recessive leucodystrophy sharing identical clinical and radiological features as X-linked Pelizaeus-Merzbacher disease. Prevalence is unknown. It is characterised by early-onset nystagmus, delayed motor milestones, progressive spasticity, ataxia, and diffuse leucodystrophy on magnetic resonance imaging.
Refers to cases of recessive X-linked ichthyosis (RXLI) that are associated with extracutaneous manifestations as part of a syndrome. It affects almost exclusively males. Cutaneous manifestations include hyperkeratosis and scaling of the skin. Non cutaneous manifestations may be corneal opacity, late puberty, cryptorchidism and a higher frequency of testicular cancer. Manifestations due to contiguous gene syndrome include neurological abnormalities such as epilepsy and hyposmia, intellectual deficit and/or short stature. Transmission is X-linked recessive.
Denotes the presence of a lesion on the cervical margin of the tooth that is not caries.
A form of axonal Charcot-Marie-Tooth disease a peripheral sensorimotor neuropathy. Presents with a more prominent muscle weakness in lower than upper limbs and frequent postural tremor.
A form of axonal Charcot-Marie-Tooth disease a peripheral sensorimotor neuropathy. Relatively late onset papillary abnormalities and deafness in most patients associated with distal weakness and muscle atrophy.
A form of axonal Charcot-Marie-Tooth disease a peripheral sensorimotor neuropathy. A late onset with severe sensory loss associated with distal weakness mainly of the legs and absent or reduced deep tendon reflexes.
A form of axonal Charcot-Marie-Tooth disease a peripheral sensorimotor neuropathy. Onset is in the first to sixth decade with a gait anomaly and a leg weakness that reaches the arms secondarily. Tendon reflexes are reduced or absent and after years all patients have a pes cavus. Other signs may be present including hearing loss and postural tremor.
A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy with distal weakness primarily and predominantly occurring in the upper limbs.Tendon reflexes are absent or reduced in the arms and decreased in the legs. Progression is slow.
A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy with the association of vocal cord anomalies, impairment of respiratory muscles, sensorineural hearing loss and weakness of hands and feet. Onset is between infancy and the sixth decade.
A rare subtype of Joubert syndrome with manifestation of the neurological features of Joubert Syndrome associated with renal disease, in the absence of retinopathy. Prevalence is unknown. In most cases the renal disease manifests as juvenile nephronophthisis, with onset of clinical symptoms in the late first/early second decade of life, although in rare cases there may be infantile nephronophthisis, with onset in the first years of life. The most commonly mutated genes in this subtype are NPHP1 (2q13) and RPGRIP1L (16q12.2) with autosomal recessive inheritance.
The most frequent subtype of Joubert syndrome with manifestation of neurological features of Joubert Syndrome associated with retinal dystrophy. Prevalence is unknown. Age of onset and severity of retinal involvement are variable, ranging from congenital to progressive retinopathy with partial conservation of vision. To date, the most frequently mutated gene in this subtype is AHI1 (6q23.2), which accounts for about 20% of cases, following autosomal recessive inheritance.
An extremely rare type of severe combined immunodeficiency characterised by the classical signs of severe combined immunodeficiency (severe and recurrent infections, diarrhoea, failure to thrive), absence of T and B lymphocytes and cell sensitivity to ionising radiation.
A rare genetic chronic skeletal disorder with characteristics of peripheral osteolysis, interphalangeal joint erosions, subcutaneous fibrocollagenous nodules, facial dysmorphism, and a wide range of associated manifestations. The prevalence and incidence of MONA are not known. Fewer than 50 cases have been reported worldwide. MONA spectrum disorders are caused by mutations in the MMP2 gene (16q13-q21) or MMP14 gene (14q11-q12). Follows an autosomal recessive pattern of inheritance. Many cases are reported in children from consanguineous unions.
An infectious embryofetopathy that has been reported to cause spontaneous abortion, stillbirth, malformations and acute systemic illness in the newborn. The clinical manifestations of congenital infection ranges from asymptomatic to benign, febrile to severe illness consisting of variable combinations of sepsis, hepatitis, coagulopathy, myocarditis, pneumonitis and meningoencephalitis.
A parasitic disease caused by Cyclospora cayetanensis, a recently discovered coccidia that was initially described in Peru and then in most intertropical zones. The prevalence is unknown. Infection occurs through ingestion of contaminated food or water and leads to abdominal pain, anorexia and diarrhea, which may resolve spontaneously in immunocompetent individuals but may persist in a chronic form in immunocompromised subjects, leading to a decline in their general state of health. The diagnosis is made by parasitological examination of the stools.
A severe form of microphthalmia with characteristics of a small eye with a short axial length, severe hyperopia, an elevated lens/eye ratio, and a high incidence of angle-closure glaucoma. Nanophthalmia is generally bilateral. Strabism is present in most patients. Mutations in the MFRP gene (11q23.1) have been found to be responsible for the hereditary form with recessive transmission. Chromosomal anomalies involving chromosome 11p and 2q11-14 have been identified for autosomal dominant forms of nanophthalmia. It may be inherited as an autosomal dominant or recessive trait, or may occur sporadically.
A rare congenital heart malformation of unknown aetiology that is characterised by an extremely dilated right atrium. It is usually asymptomatic and fortuitously discovered by echocardiography or chest radiography and can be sometimes associated with other anomalies such as atrial arrhythmias (e.g. atrial flutter, atrial fibrillation, supraventricular tachycardia), severe tricuspid regurgitation, or atrial thrombus that could lead to potentially life-threatening thromboembolic complications.
A rare benign autosomal dominant disorder of fat tissue proliferation with characteristic of presence of multiple small lipomas of 2 to 5 cm in diameter in the middle third of the body (i.e. the forearms, trunk, and upper thighs), and which are generally painless and can be easily removed provided that they are not too numerous or confluent. There have been no further descriptions in the literature since 1984.
An anatomic anomaly of the knee with characteristic of abnormal geometry of the femoral part of the patello-femoral joint. It is one of the main factors causing patellar dislocation. Present in 96% of patients with symptomatic patellar dislocation. It is observed in all ages, but is more frequent during childhood and adolescence. The femoral trochlea loses its normal concave anatomy to become flat and sometimes convex with highly asymmetrical facets. This causes a patellar tilt which could lead to patellar dislocation during knee flexion.
A rare and severe chronic disease characterised by recurrent chronic eczema mainly affecting seborrhoeic areas, a generalised fine papular rash, chronic nasal discharge with crusting of the anterior nares, and non-virulent Staphylococcus aureus or beta-hemolytic Streptococcus infections, thought to be a result of HTLV-1-induced immunosuppression.
A rare haemorrhagic disorder caused by congenital deficiency of alpha2 antiplasmin, leading to dysregulated fibrinolysis and is characterised by a haemorrhagic tendency presenting from childhood with prolonged bleeding and ecchymoses following minor trauma and spontaneous bleeding episodes. Inherited in an autosomal recessive manner.
The displacement of the urethral meatus on the ventrum of the penis. This abnormality is associated with a varyingly bent, twisted penis and opened dorsal prepuce. This congenital malformation is not rare, with an estimated prevalence of 1/1000 births but familial forms account for only 10% of cases. Hypospadias is clinically more or less severe depending on the location of the urethral opening. Familial forms are identified by determining the medical history of the family.
A rare hyperthyroidism characterised by mild to severe hyperthyroidism, presence of goitre, absence of features of autoimmunity, frequent relapses while on treatment and a positive family history.
A very rare congenital malformation syndrome with characteristics of bilateral hypoplasia of the tibia and polydactyly of the feet and hands. Prevalence is unknown but the syndrome is very rare with only a few case reports described in the literature. Additional findings include a thickened and/or duplicated fibula, hand syndactyly, and triphalangeal thumb. Autosomal dominant inheritance has been reported.
A rare subtype of type 1 autosomal dominant cerebellar ataxia with characteristics of cerebellar ataxia, tremor and cognitive impairment. Prevalence is unknown. Fewer than 80 patients affected by the disease have been identified to date. Age of onset is from 20 to 66 years. Genetic testing has shown that patients originally classified under SCA15 and SCA16 have the same subtype caused by a deletion in the inositol 1,4,5-triphosphate receptor 1 ITPR1 gene (3p26.1). Prognosis is generally good and life-shortening events do not usually occur.
An inborn error of metabolism characterised by abnormal urinary excretion of myoglobin due to acute destruction of skeletal muscle fibres. The exact prevalence remains unknown. In the majority of cases, the disease manifests in childhood and is often triggered by exertion or infection. Mutations in the mitochondrial DNA-encoded cytochrome C oxidase genes (MT-CO1 and MT-CO2) should be considered in patients with recurrent myoglobinuria.
A respiratory disease caused by the deposition of haemosiderin-laden macrophages in lungs as a result of repeated alveolar haemorrhage secondary to another disease. Seen in dysimmunitary disorders for example Heiner syndrome, thrombotic disorders and cardiovascular disorders such as mitral stenosis. It manifests as a triad of haemoptysis, anaemia and diffuse parenchymal infiltrates on chest radiography.
FRAXE is a form of nonsyndromic X-linked mental retardation with characteristic of mild intellectual deficit. The estimated prevalence in the general population is between 1 in 100,000 and 1 in 150,000. FRAXE manifests in individuals with more than 200 CCG repeats in the 5' UTR of the AFF2 gene (Xq28).
FRAXF syndrome was originally identified in a family with developmental delay and an expanded CCG repeat at the folate-sensitive FRAXF fragile site. Since this initial description, FRAXF has been associated with a range of manifestations but no clear phenotype has been established. Prevalence is unknown. The FRAXF fragile site is located at Xq28 within the 5'UTR of the TMEM185A gene.
The most rare form of primary cutaneous amyloidosis, a skin disease characterised by the accumulation of amyloid deposits in the dermis. Clinical characteristics are yellowish waxy-crusted nodules and papules on the face, lower extremities, trunk, scalp, and genitalia. Histological characteristics are the localised deposition of immunoglobulin-derived amyloid in the papillary dermis and subcutis.
Rare neuroendocrine neoplasms represented by paragangliomas (occurring in any paraganglia from the skull base to the pelvic floor) and phaeochromocytomas. Can be either hypersecreting (catecholamines) or non-secreting. There are no validated markers of malignancy (rate around 15%); the only criterion is the presence of metastases. Hereditary disease is caused by mutations in the SDHD, SDHC, SDHB, SDHA and SDHAF2 (or SDH5) genes (11q23, 1q21, 1p36.1-p35, 5p15 and 11q31.1 respectively). Transmission is autosomal dominant. The disease may be fatal, but some have lived with malignant PCC/PGL for 20 years or more.
A rare X-linked genetic epilepsy syndrome affecting females. The syndrome has characteristics of seizures starting in the first years of life and intellectual disability and may resemble Dravet syndrome. In families with this disease, male carriers are unaffected despite the X-linked inheritance.
A rare rectal disease characterised by rectal bleeding, abdominal pain, passage of mucous, sensation of incomplete evacuation, straining at defaecation and rectal prolapse, secondary to ischaemic changes in the rectum.
A recently described type of encephalitis affecting young women with teratoma of ovary and associated with antibodies that react with neuronal cell surface auto-antigens.
The syndrome is associated with a broad clinical spectrum, of which behavioral disorders and poor social interaction seem to be the most consistent. Only five patients have been reported to date. All patients have behavioral disorders suggesting that some of the genes within the duplication interval may be candidates for the autistic spectrum. Intellectual skills range from normal to mild intellectual deficiency. Other features are variable with no striking common phenotypic features.
An anatomic variant of frontotemporal dementia characterised by behavioural dysfunction, personality changes, episodic memory loss, and prosopagnosia; attributable to an asymmetrical predominantly right-sided, frontotemporal atrophy.
A chronic type of intestinal failure with characteristics of a nonfunctioning small bowel that may be reversible or irreversible. The body is unable to maintain energy and nutritional needs through absorption of food or nutrients via the intestinal tract despite being metabolically stable. This necessitates long-term parenteral feeding.
Primary dystonia DYT21 type is a subtype of mixed dystonia with a late-onset form of pure torsion dystonia.
An inherited retinal dystrophy with manifestation of severe congenital night blindness, progressive retinal dystrophy and nystagmus. Blindness is often complete by the age of 30 years.
A form of Parkinson disease with age of onset of more than 50 years, tremor at rest, gait complaints and falls, bradykinesia, rigidity and painful cramps. Patients usually present a low risk of developing non-motor symptoms, dystonia, dyskinesia and levodopa-induced dyskinesia. The exact aetiology is still unknown but mutations in the genes SNCA (4q21.3-q22), LRRK2 (12q12), and VPS35 (16q12) have been implicated in its pathogenesis. Transmission is autosomal dominant.
A benign or malignant neoplasm arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac neoplasms are rare in children. The vast majority of primary cardiac neoplasms in children are benign, whilst approximately 10% are malignant. In contrast, the majority of secondary neoplasms are malignant.
This infection causes no clinical manifestations in the majority of infants. Indeed, the occurrence of congenital infection with Epstein-Barr virus has never been demonstrated conclusively and must be very rare. One case has been reported to present after birth with multiple congenital anomalies (micrognathia, cryptorchidism, central cataracts), dystrophy and multiple areas of metaphysitis of the long bones at birth. A low birth weight was also reported.
An extremely rare inherited tumor syndrome within the familial nonmedullary thyroid cancer group.
A form of hereditary nonpolyposis colon cancer characterised by concurrent presentation of a primary tumour of the central nervous system (principally glial tumours), relatively few colonic polyps, and adenomas or colorectal carcinoma.
Dominant beta-thalassaemia is a form of beta-thalassaemia resulting in moderate to severe anaemia. Prevalence of this form is not known. Presents with moderate to severe anaemia, jaundice and splenomegaly. Rare mutations in the beta-globin HBB gene result in synthesis of extremely unstable beta-globin variants which precipitate in erythroid precursors causing ineffective erythropoiesis.
A rare form of gastric carcinoma (seen in approximately 10% of cases) with a male predominance, with characteristics of latent Epstein-Barr Virus infection in gastric carcinoma cells, diffuse-type histology, a proximal location (in the body and cardia of the stomach) and a relatively good prognosis.
Salivary gland type cancer of the breast describes a group of uncommon neoplasms, usually seen in the salivary glands but occurring in the breast, with a variable clinicopathologic spectrum and divided into those with myoepithelial differentiation and those without.
A rare ovarian germ cell malignant tumor arising from primordial germ cells, usually presenting with nausea, vomiting, abdominal pain, menstrual irregularities, and characterized by fast growth pattern, metastasis to lung, liver and brain and production of human chorionic gonadotrophin. It is apparently chemoresistant and has a worse prognosis than gestational choriocarcinoma.
Caused by the Lujo virus, a zoonotic disease from Zambia, Africa, whose reservoir is unknown. Characterised by fever and haemorrhagic manifestations with an extremely high fatality rate of 80% and a moderate to high level of nosocomial transmission.
Caused by the Chapare virus discovered from a small outbreak in Cochabamba, Bolivia between 2003 and 2004. An acute viral haemorrhagic fever characterised by fever, myalgia, arthralgia, and multiple haemorrhagic signs. About a third of untreated cases go on to develop more severe symptoms with delirium, coma and convulsions and death.
Sexual exploitation is a form of sexual abuse. Sexual exploitation of children and young people under 18 involves exploitative situations, contexts and relationships where young people receive something for example drugs, alcohol, accommodation as a result of them performing or others performing on them, sexual activities. In sexual exploitation there is financial gain from abuse.
A very rare kinetic eyelid anomaly that can affect the upper or lower eyelid, presents at birth, that in some cases can result in corneal exposure, and that may be associated with accessory levator muscle slips.
Vascular access induced steal syndrome due to a functioning arteriovenous fistula or graft.
A rare malignant sex cord stromal tumor of ovary of unknown histological lineage, occurring in adult women, characterized, in most cases, by manifestations of androgen excess (hirsutism, hair loss, amenorrhea, or oligomenorrhea) and occasionally Cushing syndrome.
The spontaneous self-limiting hygroma of infancy.
An intestinal disease characterised by an overproduction of bile acids due to a synthesis defect which leads to chronic watery diarrhoea.
A chromosomal anomaly with characteristics of severe developmental delay and/or intellectual disability, typical facial dysmorphic features, brain anomalies, seizures, cleft palate, clubfeet, nail hypoplasia and congenital heart disease.
A well-defined and clinically recognisable syndrome characterised by moderate to severe developmental delay, short stature, facial dysmorphism and variable limb defects. It has been reported in 20 patients. Dysmorphic features include microcephaly, downslanting palpebral fissures, flat and long philtrum, micrognathia and low-set and dysplastic ears. The spectrum of limb defects ranges from monodactylous ectrodactyly, brachydactyly and syndactyly to camptodactyly. The lower limbs tend to be more often and more severely affected than the upper limbs.
A form of primary progressive aphasia with characteristics of impaired single-word retrieval and naming and impaired repetition with spared single-word comprehension and object knowledge.
A very rare, severe, genetic, combined immunodeficiency disorder with characteristics of lymphocytosis, decreased peripheral CD8+ T-cells, and presence of normal circulating CD4+ T-cells, leading to immune dysfunction.
Tubular duplication of the esophagus is a rare congenital malformation where a second structure with individual lumen and stratified squamous mucosa and muscularis mucosa lies within or adjacent to the true esophagus causing dysphagia, nausea, vomiting, retrosternal pain and respiratory problems (stridor and recurrent pneumonia) and usually presenting in children.
Polyrrhinia is an extremely rare, major congenital malformation with characteristic of complete duplication of the nose resulting in two fully developed noses often associated with choanal atresia, causing respiratory distress and necessitating surgical repair.
Jeavons syndrome is an idiopathic generalised form of reflex epilepsy characterised by childhood onset, unique seizure manifestations, striking light sensitivity, and possible occurrence of generalised tonic-clonic seizures. Onset occurs in childhood, with a peak at 6-8 years of age. Eyelid myoclonia is the principle clinical feature and may or may not be associated with brief (less than 6) absences. The aetiology is unknown but Jeavons syndrome appears to be genetically determined.
Very rare poorly-defined bone disease with manifestation of ischial aplasia or hypoplasia, vertebral anomalies (vertebral malsegmentation, kyphoscoliosis), and in some patients, non-distinctive facial dysmorphism.
This syndrome has characteristics of profound conductive deafness due to stapedial abnormalities associated with variable malformations of the external ears and facial paralysis. It has been described in three siblings and their mother. Inheritance is autosomal dominant.
This syndrome is characterised by bilateral moderate-to-severe sensorineural hearing loss and salivary gland insensitivity to aldosterone resulting in hyponatraemia. It has been described in two brothers. Transmission appeared to be autosomal recessive.
A very rare and mild form of spondylocostal dysostosis with characteristics of vertebral and costal segmentation defects, often with a reduction in the number of ribs.
Rare syndrome with characteristics of camptodactyly, flattened cervical vertebral bodies and variable degrees of thoracic scoliosis. This syndrome has been described in five members from three generations of one family. Inheritance is thought to be autosomal dominant or autosomal recessive with pseudodominance.
A rare pterygium inherited autosomal dominantly, which develops in early adulthood. With characteristics of a wing-like bulbar thickening of the conjunctiva in the interpalpebral fissure area that can be cured by surgical excision.
This syndrome has characteristics of growth and developmental delay, mild to moderate neurologic abnormalities, and pili torti. It has been described in a brother and his sister born to consanguineous Puerto Rican parents.
This syndrome has characteristics of severe short stature with disproportionately short legs, small hands, clinodactyly, valvular heart disease and dysmorphism (ptosis, high-arched palate, abnormal dentition). It has been described in a mother and two daughters. This syndrome is probably transmitted as an autosomal dominant trait.
This syndrome has characteristics of short stature, sensorineural deafness, mutism, facial dysmorphism and abnormal neutrophil chemotaxis (leading to recurrent infections). It has been described in two siblings.
This syndrome has characteristics of osteoporosis, macrocephalus, brachytelephalangy, and hyperextensibility of the joints. Congenital amaurosis and intellectual deficit have also been reported. This syndrome has been described in three members of one family.
A genetic variant of Mendelian susceptibility to mycobacterial diseases with characteristics of mild bacillus Calmette-Guérin (BCG) infections and recurrent Salmonella infections. The prevalence is unknown. Over 140 cases have been reported in the world. Disease onset usually occurs in patients before the age of 12 with the appearance of BCG disease, usually after receiving the vaccination. Over half of patients with this variant experience an additional infection with non-typhoidal Salmonella. Caused by mutations in the IL12RB1 gene (19p13.1) subunit that encodes for the IL-12R-beta1 chain. These mutations impair the IL-12/IL-23 pathway essential for production of IFN-beta and the resulting immunity against Salmonella and BCG infections. Inherited in an autosomal recessive manner.
Oculocerebral dysplasia combines bilateral microphthalmia (or the association of microphthalmia and cryptophthalmus) and unilateral optic nerve aplasia. Two cases have been reported, a girl and her brother. A Dandy-Walker cyst was also present in one case. Transmission appears to be autosomal recessive.
An extremely rare fatal central nervous system malformation occurring during embryogenesis presenting prenatally on the ultrasound with holoprosencephaly and fetal hypokinesia as major features. Other manifestations include microcephaly, multiple contractures, intrauterine growth restriction. An X-linked recessive inheritance has been suggested.
This syndrome has features of microcornea, glaucoma and absent frontal sinuses. Less than 10 cases have been described so far. The mode of transmission appears to be autosomal dominant.
This syndrome has features of microcornea, which may also be accompanied by corectopia and macular hypoplasia. It has been described in three individuals from two successive generations of one family.
Periodontitis caused by the anatomic shape of the dental restoration and not the substance used.
Anatomical variation from normal tooth structure in shape, form or location.
Syndrome with the association of mullerian duct and distal limb anomalies. It has been described in five individuals from one family. Females presented with anomalies ranging from a vaginal septum to complete duplication of uterus and vagina, and males presented with micropenis. The limb anomalies varied from postaxial polydactyly to severe upper limb hypoplasia with split hand. The mode of transmission is autosomal dominant.
This syndrome associates upper limb defects (hypoplastic thumb with hypoplasia of the metacarpal bone and phalanges and delayed bone maturation), developmental delay, central hearing loss, unilateral poorly developed antihelix, bilateral choroid coloboma and growth retardation. This syndrome has been reported in two siblings. The inheritance is probably autosomal recessive.
Limb body wall complex (LBWC) is a syndrome with features of severe multiple congenital anomalies. Clinical manifestations vary widely and include limb defects and visceral malformations, spinal abnormalities, absent diaphragm, bowel atresia and renal agenesis. Karyotypes have been reported as normal and no correlations with gender, parental age and teratogenic agents have been found. The principal theories are an extrinsic origin by early amniotic rupture, or a vascular origin due to an early vascular accident during embryological development. Single cases of familial occurrence have been documented. LBWC is fatal, with death occurring antenatally or early in the neonatal period.
This syndrome has manifestation of a diffuse non-epidermolytic palmoplantar keratoderma with frequent fungal infections. Prevalence in the general population is estimated at 1 in 40,000 but is much higher in northern Sweden. Transmission is autosomal dominant and the causative gene has been localised to chromosome 12q11-q13.
A very rare syndromic limb malformation described in two distantly related boys. Its features are described as absence deformity of the left leg, progressive scoliosis, short stature, congenital cataract associated with dysplasia of the optic nerve. No intellectual deficit has been observed.
A very rare multiple congenital anomalies syndrome described in three brothers of one South-African family, and with features of hypospadias and intellectual deficit, in association with microcephaly, craniofacial dysmorphism, joint laxity and beaked nails
A very rare disorder reported in three children of consanguineous parents with manifestation of follicular hamartoma, senile facies, partial alopecia, and hypohidrosis, severely delayed growth, skin hyperelasticity and cystic fibrosis. There have been no further descriptions in the literature since 1995.
A rare copper-overload liver disease with rapidly progressive liver cirrhosis from the first few years of life leading to hepatic insufficiency. Specific pathological aspects; pericellular fibrosis, inflammatory infiltration, hepatocyte necrosis, absence of steatosis, poor regeneration and histochemical copper staining.
This syndrome is characterised by cleft lip and palate, profound sensorineural deafness and a sacral lipoma. It has been described in two brothers of Chinese origin born to non-consanguineous parents. Additional findings include appendages on the heel and thigh, or anterior sacral meningocoele and dislocated hip. The mode of inheritance is probably autosomal or X-linked recessive.
A rare autosomal dominant disorder characterised by a generalised enlargement of the gingiva occurring at birth or during childhood that is associated with generalised hypertrichosis developing at birth, during the first years of life, or at puberty and predominantly affecting the face, upper limbs, and midback.
This syndrome is characterised by Kniest dysplasia, spine abnormalities and severe dwarfism. Glaucoma has also been reported. The syndrome has been described in two unrelated children.
This syndrome has features of infantile hypotonia followed by onset of ataxia, cataract and intellectual deficit by preschool age. Cerebral atrophy also reported. It has been described in four patients from two families.
This syndrome is characterized by cataracts and short stature associated with variable anomalies, including aberrant oral frenula, a characteristic facial appearance (posteriorly angulated ears, upslanting palpebral fissures, small nose, ptosis and epicanthal folds) cavernous haemangiomas and hernias. It has been described in a mother and her two children. It is transmitted as an autosomal dominant trait.
A rare chromosomal anomaly from a variable part of chromosome 8. The phenotype of mosaic or non-mosaic supernumerary r(8)/mar(8) ranges from almost normal to variable degrees of minor abnormalities, and growth and mental retardation overlapping with the well-known mosaic trisomy 8 syndrome.
A very rare form of multiple endocrine neoplasia, an inherited cancer syndrome, with parathyroid and anterior pituitary tumors, possibly associated with adrenal, renal, and reproductive organ tumors. Caused by heterozygous inactivating mutations in the CDKN1B gene (12p13.1-p12) encoding p27, a cyclin-dependent kinase inhibitor that acts as a negative regulator of cell cycle progression. Most cases are the result of autosomal dominant inheritance. Some cases of sporadic de novo occurrence are however reported.
A surgically correctable form of primary hyperaldosteronism characterised by renin suppression, unilateral aldosterone hypersecretion, and moderate to severe hypertension secondary to hyperplasia of the adrenal gland. May be associated with hypokalaemia, which, when present, may be symptomatic with muscular weakness, cramps, paresthesia or palpitations with or without atrial fibrillation.The aetiology is not known. Unilateral adrenalectomy abolishes aldosterone hypersecretion and hypokalaemia in most patients.
Familial autosomal dominant form of arrhythmogenic right ventricular dysplasia, a heart muscle disease with life-threatening ventricular arrhythmias and left bundle branch block configuration that may manifest with palpitations, ventricular tachycardia, syncope and sudden fatal attacks.
A mild localised form of skeletal dysplasia characterised by delayed, irregular ossification of femoral capital epiphysis. Clinical manifestations may include a waddling gait, genu valgum, hip pain and restricted movement, although these manifestations are usually transient and the majority of patients are asymptomatic.
Attachment loss of greater than 2 millimeters between the gingival epithelium and the cementoenamel junction in the absence of infection or inflammation.
A rare congenital facial abnormality with manifestation of failed development of the external nose on one side that is replaced by a tubular structure composed of skin and soft tissue usually attached at the inner canthus of the eye. The disorder is therefore often associated with maldevelopment of the nasal cavity or paranasal sinuses of the affected side. Also associated with other craniofacial abnormalities such as orbital anomalies and cleft lip/palate.
A severe form of lissencephaly with cerebellar hypoplasia with main features microcephaly of at least 3 standard deviations and a thick cortex associated with complete absence of the corpus callosum.
A form of lissencephaly with cerebellar hypoplasia with main features of pronounced microcephaly, intellectual disability, spastic diplegia and moderate to severe cerebellar hypoplasia involving both vermis and hemispheres.
A severe form of lissencephaly with cerebellar hypoplasia with main features of severe microcephaly, cleft palate, and severe cerebellar and brainstem hypoplasia leading to neonatal death.
A form of lissencephaly with cerebellar hypoplasia with main features of subtle microcephaly, hypotonia and neurological and cognitive development delay. Hippocampal malformation is a characteristic feature on imaging.
Inherited or familial Creutzfeldt-Jakob disease (fCJD) is a very rare form of genetic prion disease characterised by typical CJD features (rapidly progressive dementia, personality/behavioural changes, psychiatric disorders, myoclonus, and ataxia) with a genetic cause and sometimes a family history of dementia.
RAVINE syndrome is an extremely rare genetic neurological disorder reported in a small number of patients in a specific community on Reunion Island (France) with manifestation of infantile anorexia, irrepressible and repeated vomiting, acute brainstem dysfunction, severe failure to thrive, and progressive encephalopathy with MRI showing vanishing of posterior fossa along with supra-tentorial periventricular white-matter hyperintensities and basal ganglion anomalies.
A form of potassium-aggravated myotonia which shows dramatic improvement with the use of acetazolamide. Symptoms generally manifest during childhood (before 10 years old), with myotonia of the facial, limbs and/or intercostal muscles that is triggered by potassium ingestion, fasting and mildly by cold exposure and exercise. Muscle stiffness is generally painful. Acetazolamide-responsive myotonia is a sodium muscle channelopathy due to missense mutations of the SCN4A gene, encoding the alpha subunit of the skeletal muscle voltage-gated sodium channel Nav1.4. Transmission is autosomal dominant.
A semi-dominant X-linked disease with intellectual deficiency and seizures that is more severe in male patients. Boys presenting with lissencephaly show an abnormally thick cortex with very few gyri (pachygyria) or even none (agyria). Clinical manifestations include swallowing and feeding difficulties, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe malformation referred to as ''doublecortex'' or subcortical laminar heterotopia and present with clinical signs of variable severity ranging from mild epilepsy to refractory epileptic seizures and severe intellectual deficiency. The condition is caused by doublecortin (DCX, located at Xq22.3-q23) gene mutations.
Segmental dystonia that manifests with involuntary posturing affecting predominantly the feet. The exact prevalence is unknown. The disease is reported in a limited number of Jewish and Gypsy families. The onset of the symptoms is early in childhood or adolescence.
A rare neurometabolic disorder with features of seizures, progressive encephalopathy and lens dislocation. The prevalence is unknown but is very rare. Symptoms usually occur within the first week after birth with feeding difficulties, vomiting and seizures which are difficult to control. The majority of patients exhibit facial dysmorphism. The course is progressive, with spasticity, severe intellectual deficit, and microcephaly seen in survivors. Lens dislocation usually occurs late in infancy but has been observed as early as two months of age. A late onset form with a milder phenotype has also been described. Caused by a mutation in the SUOX gene (12q13.13). The disease follows an autosomal recessive pattern of inheritance.
Main features described as symmetrical bradykinesia, predominantly axial rigidity, postural instability with early falls and cognitive decline with prominent features of frontal lobe dysfunction. Prevalence is unknown, but a higher number of cases have been described in the French West Indies. This form of atypical parkinsonism may be related to exposure to tropical plants containing mitochondrial complex I inhibitors. Guadelupian parkinsonism may actually be a tauopathy identical or closely related to progressive supranuclear palsy. Most patients are L-dopa unresponsive.
A very rare chromosomal anomaly in which both copies of chromosome 20 are inherited from the father. The main features described are high birth weight and/or early-onset obesity, relative macrocephaly, and tall stature. Most patients were ascertained through sporadic pseudohypoparathyroidism type 1b and have paternal UPD20 involving variable segments of the long arm of chromosome 20.
The Mulchandani-Bhoj-Conlin syndrome is characterized by prenatal growth restriction, severe short stature with proportional head circumference, and profound feeding difficulty (Mulchandani et al., 2016).
A distal limb malformation with manifestation of complete or partial webbing between the third and fourth fingers and/or the second and third toes. Other digits may be involved occasionally. The phenotype varies widely within and between families, sometimes only the hands are affected and sometimes only the feet. Webbing between fingers may be associated with bony fusion of the distal phalanges. Inherited as an autosomal dominant trait.
A type of multiple epiphyseal dysplasia manifesting with early onset of pain and stiffness (involving knee and hip), progressive deformity of the extremities and precocious osteoarthritis associated with delayed and irregular ossification of epiphyses. Specific features include normal stature and lesser incidence of gait abnormalities. Follows an autosomal dominant mode of transmission.
A form of multiple epiphyseal dysplasia manifesting as normal or mild short stature, pain in the hips and/or knees, progressive deformity of extremities and early onset osteoarthrosis. Specific features include a more pronounced involvement of hip joints and gait abnormality and a shorter adult height. The disease follows an autosomal dominant mode of transmission.
A congenital enteropathy presenting with early-onset severe intractable diarrhea sometimes causing irreversible intestinal failure. Infants develop a watery diarrhea within the first days after birth and the diarrhea persists in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal, rectal or esophageal atresia. Autosomal recessive transmission but the causative gene has not been yet identified.
Pituitary deficiency due to a disorder that involves the sella turcica, a bony structure at the base of the brain that surrounds and protects the pituitary gland.
A severely disabling disease with manifestation of progressive groin pain, a limping gait, leg length discrepancy, collapse of the subchondral bone, limitation of hip function and eventual degeneration of the hip joint requiring total hip arthroplasty. Familial forms appear to be very rare, with only three families identified so far. Age of onset in these familial cases ranges from 15-48. Transmission in familial cases is autosomal dominant and mutations in the type II collagen gene (COL2A1) have been detected in affected family members.
Hereditary transthyretin related systemic amyloidosis with predominant cardiac involvement resulting from myocardial infiltration of abnormal amyloid protein. Prevalence is unknown, patients present during adulthood with restrictive cardiomyopathy. Over 80 pathogenetic mutations in the TTR gene (18q12.1) have been reported so far. Transmitted as an autosomal dominant trait.
This syndrome is characterised by chronic diarrhoea in infancy or childhood in association with intestinal glucoamylase deficiency. The prevalence is unknown. Patients with chronic diarrhoea and glucoamylase deficiency may also display other disaccharidase deficiencies (sucrase, and lactase) and signs of small intestinal mucosal injury (secondary glucoamylase deficiency). No causative mutations in the maltase-glucoamylase gene have been identified so far. Patients generally respond to a starch-free diet.
Refers to a heterogeneous group of cases that are clinically diagnosed as Werner syndrome but that do not carry WRN gene mutations. Similar to classical Werner Syndrome caused by WRN mutations, patients generally exhibit an aged appearance and common age-related disorders at earlier ages compared to the general population. Compared to Werner Syndrome, it has an earlier age of onset (early 20s or earlier) and a more rapid rate of progression.
Chondrodysplasia punctata syndrome with stippled epiphyses, mild facial anomalies, short stature, and ocular colobomata. Congenital heart disease and central nervous system anomalies are also reported.
This syndrome is characterised by the association of paroxysmal dyskinesia and generalised epilepsy (usually absence or generalised tonic-clonic seizures) in the same individual or family. The prevalence is unknown. Transmission is autosomal dominant.
A rare progressive neurodegenerative disorder with typical onset between 50 and 65 years of age. Manifestation is of progressive impairment of higher visual processing skills and other posterior cortical functions without any evidence of ocular abnormalities. Prevalence is unknown, largely due to the lack of awareness of the syndrome and the inaccurate terminology referring to it. Alzheimer's disease is the most common underlying pathology, but cases attributable to Dementia with Lewy Bodies, corticobasal degeneration or prion disease have also been reported.
A rare rhythm disorder with sustained tachycardia in newborns and infants and an atrial rate often at around 440 beats/minute. May manifest as asymptomatic tachycardia, congestive heart failure or hydrops.
A congenital syndromic form of split-hand/foot malformation with features of microcephaly, microphthalmia, ectrodactyly of the lower limbs and prognathism. Intellectual deficit has been reported. MMEP syndrome is considered to be a very rare condition. Disruption of the sorting nexin 3 gene (SNX3; 6q21) has been shown to play a causative role in MMEP.
Rare syndrome with manifestations of mirror polydactyly, vertebral hypersegmentation and severe congenital limb deficiencies. Duodenal atresia and absent thymus also reported. So far, it has been described in four unrelated infants, it is suggested that the syndrome is caused by defective expression of a developmental control gene.
Rare disorder with features of severe resorption of the hands and feet and absence of the distal and middle phalanges. Other manifestations include distal muscular hypertrophy, flexion contractures, short stature, mild intellectual deficit and characteristic facies (maxillary hypoplasia, exophthalmos, and a broad nasal tip). It is transmitted as an autosomal recessive trait.
Infancy-onset olivopontocerebellar atrophy, sensorineural deafness and speech impairment. It has been described in less than 15 children. Most cases were sporadic, but autosomal recessive inheritance was suggested in three cases.
A group of symptoms which may be observed in the fetus or newborn when the mother has taken indomethacin, a nonsteroidal anti-inflammatory drug during pregnancy. The drug crosses the human placenta readily throughout gestation, but its effects on the embryo/fetus vary according to the stage of pregnancy.
This syndrome is characterised by congenital muscular dystrophy, infantile cataract and hypogonadism. Transmission appears to be autosomal recessive.
Identified in Israeli Bedouin kindred the phenotype is similar to that of Lethal congenital contracture syndrome type 2 but without distended bladder. Affected individuals are born with severe multiple joint contractures with severe muscle wasting and atrophy, mainly in the legs.
Autosomal recessive disorder originally described in Finnish families. Diagnostic criteria are early fetal hydrops and akinesia, specific neuropathology with degeneration of anterior horn neurons, and extreme skeletal muscle atrophy. The Israeli-Bedouin pedigree is characterized by congenital contractures and additional unique phenotypic abnormalities, suggesting it represents a novel variant of autosomal recessive LCCS. Features distinguishing the novel disorder, LCCS2, from the Finnish type of LCCS included additional craniofacial/ocular findings, lack of hydrops, multiple pterygia, and fractures, as well as a normal duration of pregnancy. The major unique and previously undescribed clinical feature in the Israeli Bedouin disorder is markedly distended urinary bladder.
This is an X-linked recessive retinal degenerative disease that leads to degeneration of the choriocapillaris, the retinal pigment epithelium, and the photoreceptor of the eye. Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain.
A diagnosis of exclusion, when neither associated malformations nor family history are present, and in the absence of mutations of genes known to be involved in classic lissencephaly. Clinically patients present with the common features of classic lissencephaly such as developmental delay, intellectual disability, and seizures.
Neoplasm of the heart that manifests in adults, 75% of heart tumors are benign, with myxoma being the most common benign tumor.
A rare condition characterised by generalised, partial, target tissue resistance to glucocorticoids. The clinical spectrum of the condition is broad, ranging from asymptomatic to severe cases of hyperandrogenism, fatigue and/or mineralocorticoid excess. The molecular basis of glucocorticoid resistance has been ascribed to mutations in the GR gene.
A variant of autosomal dominant optic atrophy associating typical optic atrophy with other extra-ocular manifestations such as sensorineural deafness, myopathy, chronic progressive external ophthalmoplegia, ataxia and peripheral neuropathy. More rarely, other manifestations have been associated with this condition, such as spastic paraplegia, multiple-sclerosis like illness. ADOA plus is caused by mutations in the OPA1 gene (3q29), encoding a dynamin-like GTPase involved in the fusion of the inner mitochondrial membrane. The phenotypes observed in ADOA plus are thus related to mitochondrial DNA instability resulting in multiple mitochondrial DNA deletions. Transmission is autosomal dominant with variable penetrance.
A rare autosomal recessive cerebellar ataxia characterised by progressive cerebellar ataxia associated with oculomotor apraxia, severe neuropathy, and hypoalbuminaemia. Cerebellar ataxia is the first manifestation of AOA1 with progressive gait imbalance followed by dysarthria, and limb dysmetria. Later, peripheral axonal motor neuropathy dominates the clinical picture. Oculomotor apraxia is present in almost all individuals with AOA1. Chorea is present at onset in 80% of patients and upper limb dystonia occurs in about 50% of individuals. Additional features include square wave jerks, saccadic pursuit and gaze-evoked nystagmus, areflexia followed by severe peripheral neuropathy. Variable intellectual disability is observed.
A very rare chromosomal disorder of unknown prevalence with characteristics of multiple craniofacial (microcephaly and eye, ear, and nose deformities), limb and other multiple organ abnormalities, growth and motor retardation and intellectual deficit. The syndrome is frequently lethal. The deletions include 17(q21.3q23), 17(q21.3q24.2), 17(q23.q24.3) and 17(q23.1q24.2).
Abdominal aortic aneurysm is a multifactorial disorder with multiple genetic and environmental risk factors. The disorder may occur as part of a heritable syndrome or in isolation (summary by Kuivaniemi et al., 2003). Genetic Heterogeneity of Abdominal Aortic Aneurysm Mapped loci for abdominal aortic aneurysm include AAA1 on chromosome 19q13; AAA2 (609782) on chromosome 4q31; AAA3 (611891) on chromosome 9p21; and AAA4 (614375) on chromosome 12q13.
A form of Parkinson disease with age of onset between 21 and 45 years, rigidity, painful cramps followed by tremor, bradykinesia, dystonia, gait complaints, falls and other non-motor symptoms. A slow disease progression and a more pronounced response to dopaminergic therapy are also observed in most forms. The exact aetiology is still unknown. Gene mutations have been implicated in some cases, most cases are sporadic however familial cases have been reported in which an autosomal recessive mode of inheritance has been suggested.
A rare inherited defect of the final step of aldosterone biosynthesis (conversion of deoxycorticosterone to aldosterone). It is due to mutations of the /CYP11B2/ (aldosterone synthase) gene and usually presents in infancy as a life-threatening electrolyte imbalance.
A limb girdle muscular dystrophy characterised by symmetrical and selective atrophy and weakness of proximal limb and girdle muscles without cardiac or facial disturbances.
Limb girdle muscular dystrophy characterised by limb-girdle weakness and calf pseudohypertrophy.
Congenital lactic acidosis is defined by the presence of a metabolic acidosis due to the accumulation of lactic acid in blood. Congenital defects of any one of the multiple enzymatic steps of pyruvate utilisation induce accumulation of pyruvate and lactate, but usually to levels that do not provoke metabolic acidosis. Lactic acidosis is therefore an extreme situation, due either to very severe defects or to acute metabolic crisis associated with less severe defects. It occurs mostly in neonates or very young infants, with polypnoea, severe hypotonia, lethargy, and vomiting, after a silent period during which the children were considered as normal. Facial dysmorphism and cerebral malformations may be noted, as well as diverse organ involvement such as hypertrophic myocardiopathy, tubulopathy, or liver insufficiency.
Potential for an imbalance of electrolyte levels outside the therapeutic range, providing a susceptibility to compromised health.
A group of anomalies that may result from maternal infection and subsequent fetal infection with the Herpes virus. The virus causes recurrent cutaneous infections in adults, often involving the lips or the genitalia. Herpes infections in other organs, such as the liver or central nervous system, are less frequent. Pregnancy complications including preterm delivery, intrauterine growth retardation, and neonatal infection have been attributed to the Herpes virus. Exposure of the fetus to Herpes virus at the time of delivery carries a serious risk of infection for the newborn.
Acquired developmental anomaly syndrome characterised by skin, neural, ocular, limbs and growth defects secondary to Varicella-Zoster virus infection.
Fetopathy likely to occur when a pregnant woman is infected by parvovirus B19. In adults, the virus causes a butterfly erythema infectiosum (also called Fifth Disease; 'slapped cheek disease') and flu-like symptoms with symmetric polyarthralgias.
A teratogenic disorder associated with intrauterine exposure to phenobarbital during the first trimester of pregnancy. Infants are usually asymptomatic but at an increased risk of intellectual disability, tetralogy of Fallot, unilateral cleft lip, hypoplasia of the mitral valve and some other mild abnormalities such as hypertelorism.
Abnormal accumulation of lymph in the arm, shoulder and breast area associated with surgical treatment (e.g., MASTECTOMY) or radiation treatment of breast cancer.
A cytogenetic abnormality characterized by the occurrence of a large number of chromosomal rearrangements that are restricted to sites in one or a few chromosomes. Chromothripsis may result from a single catastrophic event that causes multiple double-strand breaks, which are subsequently repaired or reassembled by error-prone DNA repair pathways or through aberrant DNA replication mechanisms.
Difference between observed and ideal DELIVERY OF HEALTH CARE and healthcare outcomes that reflect the current state of knowledge.
Acute onset of fever accompanied by seizures, cerebral inflammation and a change in mental status (e.g., confusion, disorientation, and coma).
A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment.
Genetic disorders caused by defects in genes related to the primary CILIUM; BASAL BODY; or CENTROSOME. Primary features may include obesity, SKELETAL DYSPLASIA; POLYDACTYLY and malformations that primarily involve the liver, eye or kidneys.
A statistically significant minimum set of clinical outcomes that demonstrates a clinical benefit of an intervention or treatment.
Inflammation (tendinitis) or degeneration (tendinosis) of the tendons of the elbow.
Infections with bacteria LEPTOSPIRA POMONA.
Agenesis of either mandibular second permanent molar or maxillary second permanent molar.
Absence or underdevelopment of the nasopharyngeal adenoids.
Euryblepharon is a congenital eyelid anomaly characterized by horizontal enlargement of the palpebral fissure. The eyelid is shortened vertically compared with the horizontal dimension, with associated lateral canthal malpositioning and lateral ectropion abnormally wide lid opening.
A delay in the process of formation and maturation of the epiphysis of one or more vertebrae.
Agenesis of one or more maxillary lateral incisor, comprising the maxillary lateral primary incisor.
Hyperostosis (bony overgrowth) of the mandible.
Presence of telangiectases in the oral cavity.
A neurenteric cyst located within the skull.
Feeding problem necessitating gastrojejunal tube feeding.
Tiny, repetitive muscle contractions in the eyelids, causing the appearance of twitching.
A malignant epithelial tumor with a glandular organization that originates in the intestines.
A region of high intensity (brightness) observed upon magnetic resonance imaging (MRI) scans of the spinal cord.
An abnormal decrease in the size of nasopharyngeal adenoids.
Absence of the nasopharyngeal adenoids as a developmental defect.
Underdevelopment of the nasopharyngeal adenoids.
A deviation in the size of nasopharyngeal adenoids.
A subtype of skin dimples occurring on the hands.
Reduced prothrombin antigen as measured by ELISA assay. Prothrombin is a vitamin K-dependent coagulation factor that is proteolytically cleaved to form thrombin.
Reduced level of plasminogen activator inhibitor 1 antigen.
Reduced activity of plasminogen activator inhibitor 1. This protein down-regulates fibrinolysis in the circulation by inhibiting the two major plasminogen activators: tissue-plasminogen activator and urokinase-plasminogen activator.
Abnormally decreased length of time required for an in vitro clot to dissolve in the absence of the normal plasmin inhibitors. This test is a clinical assay used to measure fibrinolysis. The euglobulin fraction of plasma is precipitated and used to form clot by addition of thrombin; after clot forms the rate of clot breakdown (fibrinolysis) can be monitored.
Reduced antithrombin antigen. A reduced level of antithrombin may lead to an increased risk of thrombus formation.
Reduced activity of alpha-2-antiplasmin. This protein inactivates the protease plasmin that drives fibrinolysis.
Increased time to coagulation in the Russell's viper venom assay
Abnormally increased length of time required for an in vitro clot to dissolve in the absence of the normal plasmin inhibitors. This test is a clinical assay used to measure fibrinolysis. The euglobulin fraction of plasma is precipitated and used to form clot by addition of thrombin; after clot forms the rate of clot breakdown (fibrinolysis) can be monitored.
Increased platelet agglutination in response to low-dose ristocetin
An increased VWF propeptide to VWF antigen indicates that deficiency of VWF is not due to impaired synthesis but due to rapid clearance. The VWF propeptide is measured by ELISA.
Increased plasma vitamin K epoxide after vitamin K supplementation is present in VKCFD (vitamin K-dependent clotting factor deficiency) type 2, but not in VKCFD type 1.
An impairment of the migration of neutrophils towards chemoattractants as part of the innate immune response
Impaired binding of factor VIII to von Willebrand Factor. This is determined using a modified ELISA assay.
The presence of intraceullar inclusion bodies (aggregates of stainable substances, usually proteins) in leukocytes.
Abnormal bleeding related to a procedure or trauma which does not start at the time of the initial insult, but after delay by at least 24 hours.
tPA catalyzes the conversion of plasiminogen to plasmin, and thus break down of clots. When there is a deficiency there will be an increase of thrombosis
Decrease of these levels result in increased inhibition of fibrinolysis and reduced inhibition of coagulation
An abnormality of coagulation related to a decreased concentration of heparin co-factor II
A decrease in high molecular weight von Willebrand factor multimers.
Clincial phenotype characterized by delayed bleeding accelerated break down of blood clot (fibrinolysis)
An increased tendency towards thrombosis in the mother during a pregnancy.
A elevation in the rate of apoptosis in lymphocytes.
A anomaly in the rate of apoptosis in lymphocytes.
Increased susceptibility to parasitic infections, as manifested by recurrent episodes of parasitic infection.
Presence of thickening of the interlobular septa of the lungs as seen on a CT scan.
FEV1/FVC less than 0.7 (FEV1 - forced expiratory volume in 1 second; FVC forced vital capacity).
A functional anomaly of that portion of the cardiosvascular system that carries deoxygenated blood from the heart to the lungs and returns oxygenated blood back to the heart.
Oxygen saturation less than 95% on exertion or arterial partial pressure of oxygen falling by more than 1kPa.
An abnormality of the cardiac ventricular function.
Osteoarthritis of facet joints in the spine. Degeneration of cartilage in the facet joints results in bone rubbing on bone and reactive new bone formation visible on X-ray.
An anomaly of the small joints located between and behind adjacent vertebrae.
Abnormally increased size of the knee joint.
Abnormal increased size of the elbow joint.
Increased concentration of amyloid in the cerebrospinal fluid (CSF).
Reduced concentration of amyloid in the cerebrospinal fluid (CSF).
Abnormal concentration of amyloid in the cerebrospinal fluid (CSF).
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the eye that is worse in certain directions of gaze and during prolonged gaze holding.
Reduced amplitude of the pulse pressure (systolic blood pressure minus diastolic blood pressure).
Heliotrope rash is a violaceous discoloration of the eyelids associated with periorbital edema.
Absent response to a pattern electroretinogram (PERG).
Incidents in which a piece of food or other objects get stuck in the upper airway and provoke coughing, gagging, inability to talk, and difficulty breathing.
Change in the color of the fundus from red in the dark-adapted state to golden immediately or shortly after the onset of the light. The color of the fundus reflex in the light adapted state has also been described as golden-yellow, gray-white, and yellow-white. This reflex can appear either homogeneous or in streaks in the fundus. The retinal vessels appear to be protruding in contrast to the radiant background. Dark adaptation leads to disappearance of the unusual fundus coloration [Digital Journal of Ophthalmology 2008; Volume 14, Number 14].
Upper eyelid partly covered by skin when eyes are open.
Lower eyelid partly covered by skin when eyes are open.
Nails that slope upward at the free edge.
Severe nail curvature, causing the tip of the nail to point downwards with respect to the axis of the finger. Beaked nails are caused by resorption of the distal digit.
A phenomenon of orange colored oral tonsils. This feature is characteristic of Tangier disease and illustrated will by Figure 1 of PMID:19470903.
The cuticle (properly known as the eponychium, or the medial nail fold or the proximal nail fold), is the thickened layer of skin surrounding fingernails and toenails. Its function is to protect the area between the nail and epidermis from exposure to bacteria. This term refers to the presence of and irregular edge or outline of the cuticle.
Nails whose growth is quicker than normal.
Lack of the lunula at the base of a nail. The lunula is the crescent-shaped whitish area of the bed of a fingernail or toenail.
A decreased ability of the eye to adjust and thereby enable sharp vision of objects at different distances.
An anomaly in the process of visual accommodation, which is the process of adjustment of the eye to enable sharp vision of objects at different distances. Accommodation is mediated by contraction of the ciliary muscles, which alter the convexity of the lens and, consequently, its refractive power.
The stria terminalis is a slender, compact fiber bundle that connects the amygdala (amygdaloid body) with the hypothalamus and other basal forebrain regions. The bed nucleus of the stria terminalis is a limbic forebrain structure that receives heavy projections from, among other areas, the basolateral amygdala, and projects in turn to hypothalamic and brainstem target areas that mediate many of the autonomic and behavioral responses to aversive or threatening stimuli. This term refers to an anomaly of the bed nucleus.
A diminished volume of the central part of the bed nucleus of the stria terminalis.
An elevated concentration of C-peptide in the circulation. Since C-peptide is secreted in equimolar amounts to insulin, this feature correlates with increased insulin secretion.
A decreased concentration of C-peptide in the circulation. Since C-peptide is secreted in equimolar amounts to insulin, this feature correlates with reduced insulin secretion.
An anomolous circulating concentration of the connecting (C) peptide, which links the insulin A and B chains in proinsulin, providing thereby a means to promote their efficient folding and assembly in the endoplasmic reticulum during insulin biosynthesis. After cleavage of proinsulin, C-peptide is stored with insulin in the soluble phase of the secretory granules and is subsequently released in equimolar amounts with insulin, providing a useful independent indicator of insulin secretion.
Abnormal enlargement in the upper jaw (maxilla) or in the lower jaw (mandible).
A structural anomaly of the jaw, the bony structure of the mouth that consists of the mandible and the maxilla.
An anomolous earwax color. Earwax (cerumen) is usually light to dark brown or orange in color.
Any anomaly of the cerumen (ear wax), the yellowish waxy substance secreted in the ear canal.
A lymphangioma (congenital malformation consisting of focal proliferations of well-differentiated lymphatic tissue in multi cystic or sponge like structures) located within the mediastinum, i.e., the central compartment of the thoracic cavity that is surrounded by loose connective tissue. Mediastinal lymphangioma is a slow growing mass with benign features, and accounts for 1% of all mediastinal tumors.
An increased concentration of interleukin-6 in the circulation.
An abnormal amount of any of the interleukins, a class of cytokines, in the circulation.
A higher than normal levels of the fatty acids which can occur in plasma as a result of lipolysis in adipose tissue or when plasma triacyglycerols are taken into tissues.
An anomaly of the protein C anticoagulant pathway, which serves as a major system for controlling thrombosis, limiting inflammatory responses, and potentially decreasing endothelial cell apoptosis in response to inflammatory cytokines and ischemia. A natural anticoagulant system denoted the protein C pathway exerts its anticoagulant effect by regulating the activity of FVIIIa and FVa. The vitamin K-dependent protein C is the key component of the pathway. Activated protein C (APC) cleaves and inhibits coagulation cofactors FVIIIa and FVa, which result in downregulation of the activity of the coagulation system. The endothelial protein C receptor stimulates the T-TM-mediated activation of protein C on the endothelial cell surface. The two cofactors, protein S and the intact form of FV, enhance the anticoagulant activity of APC.
An abnormal magnetic resonance tomography signal from a vertebral endplate with a low signal on T1 and T2-weighted sequences. Modif type III signals are thought to correspond to subchondral sclerosis seen on plain radiographs.
An abnormal magnetic resonance tomography signal from a vertebral endplate with a high signal on T1-weighted sequences and high- or isointense signal on T2 sequences. Modic type II signals are thought to indicate fatty replacement in the bone marrow.
An abnormal magnetic resonance tomography signal from a vertebral endplate with a low signal on T1-weighted sequences and high signal on T2-weighted sequences. Modic type I changes are thought to represent bone marrow edema and inflammation.
An abnormal magnetic resonance tomography signal from a vertebral endplate according to a widely used classification published by Dr. Michael Modic.
A sheet like projection that can result from uterine synechiae that has been encompassed by the expanding chorion and amnion.
An increase in mean adipocyte cell size. This feature can be measured by determining the average cell diameter of adipocytes microscopically using abdominal subcutaneous adipose tissue obtained by biopsy.
A tooth abscess that occurs at the tip of the root (apex) of a tooth.
Reddish, brown opalescent discoloration of teeth in normal light.
A teratoma located in the craniofacial region.
Loss of one twin occurring after midgestation (17 weeks gestation).
Intraventricular hemorrhage that occurs in a preterm infant and that shows parenchymal extension.
Intraventricular hemorrhage that occurs in a preterm infant and that has extension into dilated ventricles.
Intraventricular hemorrhage that occurs in a preterm infant and that has extension into normal-sized ventricles and typically fills less than 50% of the volume of the ventricle.
Intraventricular hemorrhage that occurs in a premature infant.
A type of persistance of the hyaloid vascular system associated with a retrolental mass that may lead to fetal cataract.
Persistanced of a posterior remnant of the hyaloid artery located at the optic disc.
An accessory (not normally present) muscle bundle in the right ventricle which obstructs the right ventricular outflow tract.
A type of sacrococcygeal teratoma that is predominantly intrapelvic with a small external, buttock mass.
A type of sacrococcygeal teratoma that is predominantly external but has a large intrapelvic component.
A type of sacrococcygeal teratoma that is predominantly external and projects from the sacrococcygeal region and presents with distortion of the buttocks.
An abdominal wall defected related to a developmental anomaly of the allantois, which is an embryonic structure that develops as a diverticulum off the yolk sac at about 16 days post fertilization. During further development, the allantois becomes incorporated into the body of the embryo, connecting the ventral aspect of the urogenital sinus (which will develop into the upper pole of the urinary bladder) to the external portion of the umbilicus. Upon further development, the lumen of the allantois becomes obliterated and forms a thick fibrous cord called the urachus, which connects the apex of the bladder to the umbilicus. In adults, the urachus is known as the median umbilical ligament. Failure of the allantoic cavity to obliterate can result of one of four conditions: 1) congenital patent urachus (a completely open connection between bladder and umbilicus); 2) vesicourachal diverticulum (a diverticulum off the bladder but not communicating with the umbilicus); umbilical cyst and sinus (not communicating with the bladder); and 4) alternating urachal sinus. An abdominal wall defect can be associated with a urachal cyst.
A herniation of meninges through a congenital bone defect in the skull in the parietal region.
A herniation of meninges through a congenital bone defect in the skull at the junction of the frontal and ethmoidal bones.
A neurenteric cyst located in the spine.
Dilation and elongation of the penile urethra associated with absence or hypoplasia of the corpora spongiosa and cavernosa.
Cyst on the surface of the placenta consisting of amnion and chorion.
Substantial narrowing or blockage of small pulmonary veins as a result of disorganized smooth muscle hypertrophy and collagen matrix deposition.
Decreased concentration of homovanillic acid (HVA) in the cerebrospinal fluid. HVA is a metabolite of dopamine. [KI:phemming, pmid:12615172]
Mechanical percussion (i.e., striking a muscle with a reflex hammer) leads to spreading waves of muscle contractions that begin proximally and spread laterally across the muscle. [HPO:probinson]
An usually supportive primary person (family member, significant other, or close friend) provides insufficient, ineffective, or compromised support, comfort, assistance, or encouragement that may be needed by the client to manage or master adaptive tasks related to his or her health challenge.
A subjective response indicating that something is or was a large amount.
A developmental defect resulting in the presence of fewer than the normal number of toes. [HPO:probinson]
A sterilized solution containing immunoglobulins (IGs) against cytomegalovirus (CMV) that is derived from human plasma of donors infected with CMV and can be used for passive immunization against CMV. Upon administration, human CMVIG is used to help prevent or treat infection by CMV.
Interferon omega-1 (195 aa, ~22 kDa) is encoded by the human IFNW1 gene. This protein plays a role in antiviral defense, Jak-STAT signaling pathway regulation and B- and T-cell activation.
A recombinant fusion protein derived from the coding sequences of two growth factors, interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Milodistim exhibits greater receptor binding affinity and colony stimulating activity than its parent cytokines. This agent stimulates proliferation of immature hematopoietic cells and allows the stimulation and expansion of multi-lineage hematopoiesis from immature bone marrow progenitor cells. (NCI04)
Increased numbers of mesangial cells per glomerulus, defined as four or more nuclei in a peripheral mesangial segment. [Eurenomics:fschaefer]
The unintentional discharge of a substance from a container or enclosed space.
Endometriosis that affects the vagina. It is characterized by the presence of endometrial stroma with or without endometrial-type glands in the vagina.
A common generalized epilepsy syndrome occurring in children, characterized by absence seizures of short duration. The cause of the syndrome is presumed to be genetic. Genes which are associated with the condition are GABRB3, GABRG2, GABRA1, CACNA1H, GABRA1, and GABRA5.
The presence of foam cells, a type of macrophage that localizes to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance. [HPO:probinson]
Encephalopathy that is characterized by tiny holes apparent by microscopy, often due to prion disease.
The disodium salt of a synthetic form of a naturally-occurring dipeptide consisting of L-glutamic acid and L-tryptophan with potential antiangiogenic and potential immunomodulating activities. Oglufanide inhibits vascular endothelial growth factor (VEGF), which may inhibit angiogenesis. This agent has also been reported to stimulate the immune response to hepatitic C virus and intracellular bacterial infections.
Respiratory difficulty as newborn. [HPO:probinson]
The reemergence of lymphoplasmacytic lymphoma after a period of remission.
Presence of an abnormal type of hemoglobin characterized by the subsitution of a glutamic acid residue at position 7 following the initial methionine residue by a valine (the mutation causative of sickle cell disease). The mutation promotes the polymerization of the HbS under conditions of low oxygen concentration. HbS can be identified by multiple methodologies including hemoglobin electrophoresis and high-performance liquid chromatography.
A prodrug of the monophosphate (MP) form of the antimetabolite cytarabine (araCMP), an analogue of cytidine with a modified sugar moiety (arabinose instead of ribose), with potential antineoplastic activity. Upon administration of the cytarabine MP prodrug MB07133, the targeting moiety of this agent specifically delivers the cytarabine moiety to the liver. In turn, araCMP is selectively converted to araC triphosphate (araCTP) by a liver kinase, where it binds to and competes with cytidine for incorporation into DNA, thereby inhibiting DNA polymerase, and DNA synthesis. This leads to the inhibition of tumor cell proliferation and destruction of liver cancer cells. The liver is not able to convert araC into araCMP; araCMP is not converted into araCTP in tissues other than the liver. This enhances efficacy and minimizes systemic toxicity.
Persistent patency of the ductus arteriosus, or patent ductus arteriosus (PDA), is the second most common congenital heart disease, affecting approximately 1 in 1,600 to 5,000 live births in the U.S. (Mitchell et al., 1971). In fetal life, the ductus arteriosus, a muscular artery, shunts blood from the pulmonary artery to the aorta, bypassing the lungs. Its abrupt closure at birth establishes the mature circulatory pattern and represents a dramatic example of vascular remodeling. Failure of this normal process results in persistent PDA, which left untreated can result in pulmonary hypertension and heart failure. Closure of the ductus is a complex process. Aspects of this process are regulated by oxygen tension and a decrease in levels of hormones such as prostaglandin E2. PDA occurring in preterm infants often closes spontaneously or in response to inhibitors of prostaglandin biosynthesis (Ramsay et al., 1987). Term PDA typically has not been regarded as a genetic disorder, because it most often occurs sporadically. Nonetheless, term PDA recurs among 5% of sibs of PDA cases (Polani and Campbell, 1960; Lamy et al., 1957), suggesting a genetic component to disease pathogenesis that has typically been presumed to be multifactorial. That single genes can influence this trait has been demonstrated by a mouse model of PDA resulting from disruption of the prostaglandin E2 receptor (Nguyen et al., 1997) and by rare syndromic forms of PDA such as Char syndrome (169100), an autosomal dominant disorder caused by mutations in the transcription factor TFAP2B (601601) (Mani et al., 2002). Genetic Heterogeneity of Patent Ductus Arteriosus Autosomal dominant forms of patent ductus arteriosus include PDA2 (617035), caused by mutation in the TFAP2B gene (601601) on chromosome 6p12, and PDA3 (617039), caused by mutation in the PRDM6 gene (616982) on chromosome 5q23. Hajj and Dagle (2012) reviewed the genetics of patent ductus arteriosus in both term and preterm infants, and discussed possible environmental risk factors as well as animal models of PDA.
A pruritic rash that occurs as consequence of cercariae penetration of the skin after aquatic exposure to animal (usually avian) schistosomes, often in countries non-endemic to human schistosomiasis. The condition is non-invasive and responsive to symptomatic treatment.
An orally bioavailable small molecule antagonist of the Hedgehog (Hh)-ligand cell surface receptor smoothened (Smo) with potential antineoplastic activity. Taladegib inhibits signaling that is mediated by the Hh pathway protein Smo, which may result in a suppression of the Hh signaling pathway and may lead to the inhibition of the proliferation of tumor cells in which this pathway is abnormally activated. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair; constitutive activation of this pathway is associated with uncontrolled cellular proliferation and has been observed in a variety of cancers.
Sialidosis is an autosomal recessive disorder characterized by the progressive lysosomal storage of sialylated glycopeptides and oligosaccharides caused by a deficiency of the enzyme neuraminidase. Common to the sialidoses is the accumulation and/or excretion of sialic acid (N-acetylneuraminic acid) covalently linked ('bound') to a variety of oligosaccharides and/or glycoproteins (summary by Lowden and O'Brien, 1979). The sialidoses are distinct from the sialurias in which there is storage and excretion of 'free' sialic acid, rather than 'bound' sialic acid; neuraminidase activity in sialuria is normal or elevated. Salla disease (604369) is a form of 'free' sialic acid disease. Classification Lowden and O'Brien (1979) provided a logical nosology of neuraminidase deficiency into sialidosis type I and type II. Type I is the milder form, also known as the 'normosomatic' type or the cherry red spot-myoclonus syndrome. Sialidosis type II is the more severe form with an earlier onset, and is also known as the 'dysmorphic' type. Type II has been subdivided into juvenile and infantile forms. Other terms for sialidosis type II are mucolipidosis I and lipomucopolysaccharidosis.
Polydactyly refers to the occurrence of supernumerary digits and is the most frequent of congenital hand and foot deformities. Based on the location of the extra digits, polydactyly can be classified into preaxial, involving the thumb or great toe; postaxial, affecting the fifth digit; and central, involving the 3 central digits. Postaxial polydactyly (PAP) is further subclassified into 2 types: in type A, a well-formed extra digit articulates with the fifth or a sixth metacarpal, whereas in type B, a rudimentary, poorly developed extra digit is present (summary by Umm-e-Kalsoom et al., 2012). Genetic Heterogeneity of Postaxial Polydactyly Other forms of postaxial polydactyly type A include PAPA2 (602085) on chromosome 13q21; PAPA3 (607324) on chromosome 19p13; PAPA4 (608562) on chromosome 7q22; PAPA5 (263450) on chromosome 13q13; PAPA6 (615226), caused by mutation in the ZNF141 gene (194648) on chromosome 4p16; PAPA7 (617642), caused by mutation in the IQCE gene (617631) on chromosome 7p22; and PAPA8 (618123), caused by mutation in the GLI1 gene (165220) on chromosome 12q13.
Decreased density/number and/or decreased diameter of eyebrow hairs. [pmid:19125427]
Disease with characteristics of delayed motor development, hypotonia and progressive neurodegeneration. To date, it has been described in four boys. The syndrome is caused by mutations affecting the two alleles of the HIBCH gene, encoding 3-hydroxyisobutyryl-CoA hydrolase which is caused by homozygous or compound heterozygous mutation in the HIBCH gene on chromosome 2q32.
A finding of complete pharyngeal contraction during swallowing.
A finding of oral residue remaining on palate after an individual swallows.
A change in the nucleotide sequence of the PMS1 gene.
A change in the nucleotide sequence of the MSH2 gene.
A finding of oral residue remaining on tongue after an individual swallows.
A triphenylmethane-based dye and an inhibitor of nicotinamide adenine dinucleotide phosphate (NADP+) oxidase 4 (NOX4), with potential anti-invasive and anti-oxidative activities. Upon administration, imipramine blue (IB) inhibits the activity of NOX4 and prevents NOX4-mediated cell signaling. This prevents the formation of NOX4-mediated reactive oxygen species (ROS), abrogates the ROS-induced inhibition of protein tyrosine phosphatase (PTP) activation, and induces both G2/M cell cycle arrest and apoptosis. NOX4, an enzyme belonging to the NOX family of proteins, promotes the production of ROS and plays a key role in the suppression of PTP activation; it is upregulated in a variety of cancers.
A condition of decreased or absent presence or activity of IL2-inducible t-cell kinase. Deficiency of this protein is associated with lymphoproliferative syndrome 1, an autosomal recessive primary immunodeficiency characterized by onset in early childhood of Epstein-Barr virus (EBV)-associated immune dysregulation, manifest as lymphoma, lymphomatoid granulomatosis, hemophagocytic lymphohistiocytosis, Hodgkin disease, and/or hypogammaglobulinemia..
A response indicating that an individual stayed off cigarettes less than one month since their diagnosis.
A response indicating that it has been less than one month since an individual smoked a cigarette.
A response indicating that an individual stayed off cigarettes more than one year since their diagnosis.
A response indicating that it has been more than one year since an individual smoked a cigarette.
An NIH skin score that has increased by 1 or more points, except 0 to 1.
Either a decrease by 10% predicted absolute value of %FEV1 or an NIH lung symptom score that has increased by 1 or more points, except 0 to 1.
A WHO grade III pleomorphic xanthoastrocytoma characterized by the presence of five or more mitoses per 10 high-power fields. Necrosis may be present. Patients have shorter survival rates when compared to those with WHO grade II pleomorphic xanthoastrocytoma.
An autosomal dominant genetic disorder caused by mutations in the CDKN2A gene, encoding cyclin-dependent kinase inhibitor 2A. The condition is characterized by cutaneous malignant melanoma associated with this genetic alteration.
Autosomal dominant deafness-66 is a form of nonsyndromic sensorineural hearing impairment with widely variable age at onset (Nyegaard et al., 2015).
Tonne-Kalscheuer syndrome (TOKAS) is an X-linked recessive multiple congenital anomaly disorder with 2 main presentations. Most patients exhibit global developmental delay apparent from early infancy, impaired intellectual development, speech delay, behavioral abnormalities, and abnormal gait. Affected individuals also have dysmorphic facial features that evolve with age, anomalies of the hands, feet, and nails, and urogenital abnormalities with hypogenitalism. A subset of more severely affected males develop congenital diaphragmatic hernia in utero, which may result in perinatal or premature death. Carrier females may have very mild skeletal or hormonal abnormalities (summary by Frints et al., 2018). Also see Fryns syndrome (229850), an autosomal recessive disorder with overlapping features.
An assessment of an individual's oral impairment during swallowing.
A nutritional supplement containing an extract obtained from the French maritime pine bark Pinus pinaster, with potential immunomodulating and antioxidant activities. The French maritime pine bark extract contains high amounts of the phytochemicals proanthocyanidins. Proanthocyanidins are able to scavenge free radicals, and therefore may inhibit cellular damage. This extract may also ameliorate the symptoms of lymphedema and improve blood flow. It might also stimulate the immune system and have antioxidant effects.
A traditional Chinese medicine (TCM) composed of Polyporus sclerotium (Sclerotium polypori Umbrellati; Zhu Ling), Sclerotium Poriae Cocos (Poria; Fu Ling), Alismatis rhizome (Alisma; Rhizoma Alismatis Orientalis; Ze Xie), Cinnamomi cortex (Ramulus Cinnamomi Cassiae; Gui Zhi) and Atractylodis macrocephalae rhizome (Rhizoma Atractylodis Macrocephalae; Bai Zhu) with potential diuresis-inducing and kidney protective activities. Upon oral administration, wu-ling san may increase the removal of excess fluid, prevent the retention of water, maintain healthy water metabolism by promoting diuresis, and protect kidney function.
A condition of decreased or absent presence or activity of SH2 domain protein 1A. Deficiency of this protein is associated with X-linked lymphoproliferative syndrome 1 (Duncan Disease).
A decrease in the size and extent of tissue involvement by cancer, accompanied by an increase in blood lymphocyte count above a predetermined threshold.
Ovarian cancer involving 1 or both ovaries with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes. (FIGO, 2014)
MIRAGE syndrome is a form of syndromic adrenal hypoplasia, characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy. The condition is often fatal within the first decade of life, usually as a result of invasive infection (Narumi et al., 2016).
A response indicating that no time was spent on an activity.
A response indicating that an individual used videos to quit smoking cigarettes.
A condition associated with mutation(s) in the DNAJC5 gene, encoding dnaJ homolog subfamily C member 5. The condition is one of a group of genetically heterogeneous neurodegenerative disorders, characterized by accumulation of intracellular lipopigments.
A response indicating that an individual doesn't know or remember if they stayed off cigarettes since their diagnosis.
A response indicating that an individual doesn't know and/or remember how long it has been since they last smoked a cigarette.
A finding of residue on pharyngeal wall following swallowing.
A recombinant, soluble form of the human protein thrombomodulin, with potential anticoagulant activity. Upon administration, thrombomodulin binds to thrombin, which stimulates the activation of protein C. Activated protein C (APC) degrades factor Va and Factor VIIa in the presence of the cofactor protein S, inhibits thrombin formation, and prevents both thrombin-mediated coagulation and further clot formation.
Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease.
A change in the amino acid residue at position 515 in the thrombopoietin receptor protein where tryptophan has been replaced by lysine.
A change in the amino acid residue at position 515 in the thrombopoietin receptor protein where tryptophan has been replaced by leucine.
An observation of an individual's larygeal elevation during swallowing.
Spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) is an autosomal dominant neurologic disorder characterized by rapid growth in infancy, global developmental delay, spastic paraplegia, variable ophthalmologic defects, and dysmorphic facial features (summary by Josifova et al., 2016).
The ductus arteriosus is a muscular artery connecting the pulmonary artery and the aorta during fetal life, shunting blood away from the lungs. It normally occludes shortly after birth. Failure of ductal closure results in PDA, one of the most common congenital heart defects, affecting 1 in 2,000 to 1 in 5,000 full-term infants and constituting 5% to 7% of all congenital heart defects (summary by Mani et al., 2005). PDA can be an isolated anomaly or occur in association with other congenital anomalies (summary by Khetyar et al., 2008). For a discussion of genetic heterogeneity of isolated PDA, see PDA1 (607411).
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is a genetically heterogeneous autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and early death. The phenotype commonly includes cobblestone (type II) lissencephaly, cerebellar malformations, and retinal malformations. More variable features include macrocephaly or microcephaly, hypoplasia of midline brain structures, ventricular dilatation, microphthalmia, cleft lip/palate, and congenital contractures (Dobyns et al., 1989). Those with a more severe phenotype characterized as Walker-Warburg syndrome often die within the first year of life, whereas those characterized as having muscle-eye-brain disease may rarely acquire the ability to walk and to speak a few words. These are part of a group of disorders resulting from defective glycosylation of DAG1 (128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007). Genetic Heterogeneity of Congenital Muscular Dystrophy-Dystroglycanopathy with Brain and Eye Anomalies (Type A) Muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is genetically heterogeneous and can be caused by mutation in other genes involved in DAG1 glycosylation: see MDDGA2 (613150), caused by mutation in the POMT2 gene (607439); MDDGA3 (253280), caused by mutation in the POMGNT1 gene (606822); MDDGA4 (253800), caused by mutation in the FKTN gene (607440); MDDGA5 (613153), caused by mutation in the FKRP gene (606596); MDDGA6 (613154), caused by mutation in the LARGE gene (603590); MDDGA7 (614643), caused by mutation in the ISPD gene (614631); MDDGA8 (614830) caused by mutation in the GTDC2 gene (POMGNT2; 614828); MDDGA9 (616538), caused by mutation in the DAG1 gene (128239); MDDGA10 (615041), caused by mutation in the TMEM5 gene (RXYLT1; 605862); MDDGA11 (615181), caused by mutation in the B3GALNT2 gene (610194); MDDGA12 (615249), caused by mutation in the SGK196 gene (POMK; 615247); MDDGA13 (615287), caused by mutation in the B3GNT1 gene (B4GAT1; 605517); and MDDGA14 (615350), caused by mutation in the GMPPB gene (615320).
A finding of residue on tongue base following swallowing.
Decreased activity of the enzyme 3-beta-hydroxysteroid dehydrogenase, associated with mutation(s) in the HSD3B2 gene. The lack of activity of this enzyme produces a type of congenital adrenal hyperplasia.
An observation of the location of pharyngeal residue remaining after an individual swallows.
An observation of the location of oral residue remaining after an individual swallows.
A finding of an absent pharyngeal stripping wave.
A rare B-cell non-Hodgkin lymphoma that is characterized by the abnormal rearrangement of two genes, MYC gene and either BCL2 or BCL6 genes. Patients with this type of lymphoma usually respond poorly to standard treatments and have a poor prognosis.
An observation of an individual's lip closure during swallowing.
Ovarian cancer involving one or both ovaries with pelvic extension (below the pelvic brim) or primary peritoneal cancer. (FIGO, 2014)
A nucleotide substitution at position *97 in the 3' untranslated region of the F2 gene where guanine has been mutated to adenine.
A hemostatic powder composed of hydrophilic, absorbable modified polymers (AMPs) derived from plant starch, with potential anti-hemorrhagic activity. Upon local administration of the AMP hemostatic powder directly sprayed over the bleeding surface, this powder adheres to the bleeding area, and the AMPs are able to absorb fluid and therefore soak up blood at the bleeding site. This leads to the formation of a gelled matrix that seals the affected site, and allows platelets, red blood cells and clotting factors in the blood to concentrate at the wound. In turn, this promotes the coagulation cascade, helps to stop or control bleeding, and prevents further blood loss. The AMP particles are naturally degraded by human enzymes over time.
Methemoglobinemia and ambiguous genitalia is due to isolated 17,20-lyase deficiency, defined by apparently normal 17-alpha-hydroxylase activity but severely reduced 17,20-lyase activity of the CYP17A1 enzyme (609300), which results in sex steroid deficiency but normal glucocorticoid and mineralocorticoid reserve. The clinical phenotype is characterized by male undermasculinization, with absent or disturbed pubertal development in both 46,XY and 46,XX individuals. Mild to severe methemoglobinemia has been reported in these patients (Idkowiak et al., 2012). Other autosomal recessive methemoglobinemias include types I and II (see 250800), caused by mutation in the CYB5R3 gene (613213). Isolated 17,20-lyase deficiency can also be caused by mutation in the CYP17A1 gene (609300), and mutation in the POR gene can manifest clinically as isolated 17,20-lyase deficiency (see 124015.0016).
Ovarian cancer with macroscopic, extrapelvic, peritoneal metastasis equal or less than 2 cm +/- positive retroperitoneal lymph nodes. Includes extension to capsule of liver/spleen. (FIGO, 2014)
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in a carotid artery.
A combination preparation containing the third-generation cephalosporin ceftazidime and the sodium salt form of avibactam, a non-beta-lactam beta-lactamase inhibitor, with antibiotic and beta-lactamase inhibiting activity, respectively. Upon administration, ceftazidime binds to essential penicillin-binding proteins (PBPs) and inhibits cell wall synthesis in certain bacteria. Avibactam binds to and inactivates beta-lactamases, thereby protecting ceftazidime from degradation and increasing ceftazidime's efficacy.
A non-invasive serous carcinoma arising from the fallopian tube.
A recently proposed term intended to replace the existing term of noninvasive encapsulated follicular variant papillary thyroid gland carcinoma. The nomenclature change results in removal of the term carcinoma from this group of neoplasms. These neoplasms are characterized by the absence of capsular or vascular invasion; a follicular growth pattern with less than 1% papillae; no evidence of high mitotic activity (3 or less mitoses/10HPF); nuclear features of papillary thyroid gland carcinoma; and the absence of tumor necrosis or psammoma bodies. The prognosis is good.
Tissue derived from portions of the placenta donated by the patient during a C-section, with potential regenerative activity. Upon placement of the tissue around or on the affected area, dehydrated human amnion/chorion membrane (dHCAM), which contains regenerative cytokines, promotes wound angiogenesis and may help heal the wound, restore tissue function and reduce risk of inflammation.
A rare, high grade sarcoma that arises from the endometrial stroma. It is characterized by round cell morphology. It was previously also known as undifferentiated uterine sarcoma. In 2014, high grade endometrial stromal sarcoma was reclassified and is currently considered a distinct and rare neoplasm. It appears to have a prognosis that falls between low grade endometrial stromal sarcoma and undifferentiated sarcoma.
A synthetic vaccine consisting of hemagglutinin (HA) antigens derived from four inactivated influenza viruses, two different influenza type A strains and two different influenza type B strains, with protective immunizing activity. Quadrivalent influenza vaccine (QIV) is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. Upon administration, the QIV provides active immunization against the four influenza virus strains, thereby protecting against influenza infection.
A lipid-based nanoparticle formulation composed of liposomes encapsulating a small oligonucleotide encoding a small activating RNA (saRNA) targeting the CCAAT enhancer binding protein alpha (CEBPA; C/EBP-a) gene, with potential antineoplastic activity. Although the exact mechanism of action through which saRNAs exert their effect(s) is still largely being investigated, it appears that, upon administration, the CEBPA-targeting saRNA MTL-CEBPA liposome targets and binds to a specific DNA regulatory target region, most likely the promoter region, for the CEBPA gene. This restores CEBPA gene transcription, and increases both CEBPA mRNA levels and protein expression. This in turn activates the expression of tumor suppressor genes and may halt proliferation of susceptible tumor cells. Specifically, upregulation of CEBPA in liver cells abrogates liver cancer cell proliferation, thereby prevents liver failure and normalizes liver function. CEBPA, a transcription factor that plays a key role in the regulation of the expression of genes with many functions, including those involved in cellular proliferation, metastasis and normal hepatocyte function, is found in many tissues, including liver cells, adipose tissue and myeloid cells. CEBPA is downregulated in certain types of cancer cells, such as liver cancer cells. saRNA is a short, double-stranded RNA that is structurally related to siRNAs; saRNA is most likely to bind to a target site on the promoter of the CEBPA gene and upregulates its gene expression.
A humanized monoclonal antibody targeting leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), with potential antineoplastic activity. Upon administration, the anti-LGR5 humanized monoclonal antibody BNC101 targets and binds to LGR5, thereby inhibiting LRG5-mediated signal transduction pathways. This prevents proliferation of LRG5-expressing tumor cells. LGR5, a member of the Wnt signaling pathway, is a cancer stem cell (CSC) receptor overexpressed on certain cancer cells; it plays a key role in CSC proliferation and survival.
A papillary carcinoma of the thyroid gland which is encapsulated and resembles an encapsulated follicular neoplasm. The malignant follicular cells display the nuclear features that characterize the papillary adenocarcinomas of the thyroid gland. Despite the complete encapsulation, metastasis can occur.
A recombinant fusion protein composed of the extracellular domain of the mature human glycoprotein CD24 linked to a human immunoglobulin G1 (IgG1) Fc domain, with potential immune checkpoint inhibitory, anti-inflammatory and antineoplastic activities. Upon administration, the CD24 extracellular domain-IgG1 Fc domain recombinant fusion protein CD24Fc binds to injured cell components, also called DAMPs (Danger-Associated Molecular Patterns), thereby preventing the interaction of DAMPs with toll-like receptors (TLRs) and inhibiting both nuclear factor-kappa B (NFkB) activation and secretion of inflammatory cytokines. In addition, CD24Fc binds to and activates Siglec G/10, a sialic acid-binding immunoglobulin-type lectin, and stimulates SHP-1-mediated inhibitory signaling, while also preventing NFkB activation and secretion of inflammatory mediators, which further prevents inflammatory responses. DAMPs activate the innate immune system. CD24 binds to both DAMPs and Siglec G/10 to regulate immune responses.CD24/Siglec G/10 interaction plays a key role in a number of immune-mediated diseases including graft-versus-host disease (GvHD), multiple sclerosis and rheumatoid arthritis.
An orally bioavailable pan inhibitor of the serine/threonine protein kinase AKT (protein kinase B) enzyme family with potential antineoplastic activity. Upon oral administration, AKT inhibitor ARQ 751 selectively binds to and inhibits the activity of the AKT isoforms 1, 2 and 3, which may result in the inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. This may lead to a reduction in tumor cell proliferation and the induction of tumor cell apoptosis. The AKT signaling pathway is often deregulated in cancer and is associated with tumor cell proliferation, survival and migration.
An orally bioavailable small molecule inhibitor of the oncoprotein c-Met (hepatocyte growth factor receptor; HGFR), with potential antineoplastic activity. Upon oral administration, HS-10241 targets and binds to the c-Met protein, prevents c-Met phosphorylation and disrupts c-Met-dependent signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.
A mixture of two humanized immunoglobulin G1 (IgG1) monoclonal antibodies, Hu9006 and Hu9338, which recognize non-overlapping epitopes in the extracellular domain of the human hepatocyte growth factor receptor (MET; HGFR; c-Met), with potential antineoplastic activity. Upon administration, anti-MET monoclonal antibody mixture Sym015 targets and binds to the extracellular domain of MET, thereby preventing the binding of its ligand, hepatocyte growth factor (HGF). This may prevent activation of the receptor and MET-mediated signal transduction pathways. This inhibits MET-dependent tumor cell proliferation. MET, a receptor tyrosine kinase, is overexpressed on the cell surfaces of various solid tumor cell types; it plays a key role in cancer cell growth, survival, angiogenesis, invasion, and metastasis.
An orally administered inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2; ROCK-II), with potential immunomodulating activity. Upon administration, ROCK2 inhibitor KD025 binds to and inhibits the serine/threonine kinase activity of ROCK2. This inhibits ROCK2-mediated signal transduction pathways and modulates various pro- and anti-inflammatory immune cell responses. ROCK2 is upregulated in various diseases, including various fibrotic, neurodegenerative and autoimmune diseases.
An orally bioavailable, selective inhibitor of the dual specificity protein kinase TTK (monopolar spindle 1 kinase, Mps1), with potential antineoplastic activity. Upon administration, the Mps1 inhibitor CFI-402257 selectively binds to and inhibits the activity of Mps1. This inactivates the spindle assembly checkpoint (SAC) and accelerates mitosis, which results in chromosomal misalignment and missegregation, and mitotic checkpoint complex destabilization. This induces cell death in Mps1-overexpressing cancer cells. Mps1, a tyrosine and serine/threonine kinase expressed in proliferating normal tissues, is essential for proper SAC functioning and chromosome alignment. Overexpressed in various human tumors, Mps1 plays a key role in uncontrolled tumor cell growth.
A human immunoconjugate (ICON) fusion protein composed of a modified version of human factor VII (FVII) which targets tissue factor (TF) that is fused to the Fc domain of the human immunoglobulin G1, with potential anti-thrombotic and antineoplastic activities. Acting in a similar manner as plasma FVII, the natural ligand of TF, ICON-1 targets and binds to TF expressed on neovascular endothelia, thereby preventing TF-mediated signaling pathways, and leading to the initiation of an immune response and the destruction of neovascular tissue. This prevents angiogenesis, inflammation and blood coagulation. Upon intravitreal administration, ICON-1 may block TF-induced angiogenesis and treat wet age-related macular degeneration (AMD) and ocular melanoma. TF, a naturally occurring glycoprotein in humans, regulates blood clotting, angiogenesis, and inflammation.
An orally available, small molecule and selective ATP-competitive pan-inhibitor of proviral integration sites for Moloney murine leukemia virus (PIM) kinases, with potential antineoplastic activity. Upon oral administration, pan-PIM kinase inhibitor NVP-LGB-321 binds to and prevents the activation of the three PIM family kinases, PIM1, PIM2 and PIM3. This prevents the activation of PIM-mediated signaling pathways and inhibits proliferation in cells that overexpress PIMs. PIMs, constitutively active proto-oncogenic serine/threonine kinases upregulated in various types of cancers, play key roles in tumor cell proliferation and survival.
A traditional Chinese medicine (TCM) decoction containing Herba Epimedii that can be used for chemotherapy-induced hand-foot syndrome (HFS; Palmar-Plantar Erythrodysesthesia; PPE). Soaking of the affected hands and feet with TCM Formula LC09 may reduce the severity of HFS and may decrease HFS-associated pain.
An inhibitor of induced myeloid leukemia cell differentiation protein MCL-1 (myeloid cell leukemia-1), with potential pro-apoptotic and antineoplastic activities. Upon administration, AMG 176 binds to and inhibits the activity of MCL-1. This disrupts the formation of MCL-1/Bcl-2-like protein 11 (BCL2L11; BIM) complexes and induces apoptosis in tumor cells. MCL-1, an anti-apoptotic protein belonging to the Bcl-2 family of proteins, is upregulated in cancer cells and promotes tumor cell survival.
An orally bioavailable inhibitor of the bromodomain and extra-terminal (BET) family of proteins, with potential antineoplastic activity. Upon oral administration, the BET inhibitor ZEN-3694 binds to the acetylated lysine recognition motifs in the bromodomains of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of proliferation in BET-overexpressing tumor cells. BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.
An anti-CD123/anti-CD3 bispecific monoclonal antibody, in which most of the naturally-occurring Fc domain is maintained, with potential immunostimulatory and antineoplastic activities. Anti-CD123/CD3 monoclonal antibody XmAb14045 possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for CD123, a tumor-associated antigen (TAA) overexpressed on the surface of certain tumor cells. Upon administration of XmAb14045, this bispecific antibody simultaneously binds to both CD3-expressing T-cells and CD123-expressing cancer cells, thereby crosslinking CD123-expressing tumor cells and cytotoxic T-lymphocytes (CTLs). This may result in potent CTL-mediated cell lysis of CD123-expressing tumor cells. CD123, the interleukin-3 receptor alpha chain, is overexpressed in a variety of hematological malignancies; its expression is low or absent in normal hematopoietic progenitors and stem cells. The Fc domain on the antibody prolongs the half-life of the bispecific antibody and enhances T-cell mediated tumor cell killing through its binding to the Fc receptors.
An orally bioavailable inhibitor of C-X-C chemokine receptor type 4 (CXCR4), with potential antineoplastic and immune checkpoint inhibitory activities. Upon administration, the CXCR4 inhibitor X4P-001 selectively binds to CXCR4 and prevents the binding of CXCR4 to its ligand, stromal cell-derived factor 1 (SDF-1 or CXCL12). This inhibits receptor activation and results in decreased proliferation and migration of CXCR4-overexpressing tumor cells. In addition, inhibition of CXCR4 prevents the recruitment of regulatory T-cells and myeloid-derived suppressor cells (MDSCs) to the tumor microenvironment, thereby abrogating CXCR4-mediated immunosuppression and enabling the activation of a cytotoxic T-lymphocyte-mediated immune response against cancer cells. The G protein-coupled receptor CXCR4, which is upregulated in several tumor cell types, induces the recruitment of immunosuppressive cells in the tumor microenvironment, suppresses immune surveillance, and promotes tumor angiogenesis and tumor cell proliferation. It is also a co-receptor for HIV entry into T-cells.
An ATP-competitive inhibitor of the catalytic subunit of DNA-dependent protein kinase (DNA-PK), with potential sensitizing and enhancing activities for both chemo- and radiotherapies. Upon administration, DNA-PK inhibitor VX-984 binds to and inhibits the catalytic subunit of DNA-PK, thereby interfering with the non-homologous end joining (NHEJ) process and preventing repair of DNA double strand breaks (DSBs) caused by ionizing radiation or chemotherapeutic treatment. This increases chemo- and radiotherapy cytotoxicity and leads to enhanced tumor cell death. The enhanced ability of tumor cells to repair DSBs plays a major role in the resistance of tumor cells to chemo- and radiotherapy; DNA-PK plays a key role in the NHEJ pathway and DSB repair.
A human monoclonal antibody against human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon administration, U3-1784 specifically binds to and blocks FGFR4. This prevents the activation of FGFR4, inhibits FGFR4-mediated signaling and leads to an inhibition of cell proliferation in FGFR4-overexpressing tumor cells. FGFR4, a receptor tyrosine kinase overexpressed by certain tumor cell types, is involved in tumor cell proliferation, differentiation, angiogenesis, and survival.
A fusion protein consisting of a peptide sequence of human papillomavirus (HPV) type 16 E7 nuclear protein and fused to the Pseudomonas aeruginosa exotoxin A (PE) and a endoplasmic reticulum (ER) retention signal (KDEL), with potential antineoplastic activity. Upon administration of PE/HPV16 E7/KDEL fusion protein TVGV-1, the PE moiety binds to CD91 (LRP1) expressed on a variety of cells, including antigen-presenting cells such as dendritic cells (DCs), which facilitates the internalization, through endocytosis, of TVGV-1. Following endocytosis, this agent is proteolytically cleaved by the proteosome and the epitopes from the HPV E7 protein become bound to MHC-I molecules and are presented on the DC-cell surface. This facilitates a cytotoxic T-cell- mediated immune response against HPV16 E7 expressing-tumor cells. KDEL targets the fusion protein to the ER, which increases this agent's potential to be bound by MHC-I molecules; this increases the immune response against HPV16 E7-expressing cancer cells.
A monoclonal antibody against the inhibitory T-cell receptor, T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3; TIM3; hepatitis A virus cellular receptor 2; HAVCR2), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the anti-TIM-3 monoclonal antibody TSR-022 binds to TIM-3 expressed on certain T-cells, including tumor infiltrating lymphocytes (TILs). This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which results in a reduction in tumor growth. TIM-3, a transmembrane protein and immune checkpoint receptor, is associated with tumor-mediated immune suppression.
A peptide vaccine containing five immunogenic peptide epitopes of the human folate receptor 1 (FOLR1; FR-alpha), with potential immunomodulating and antineoplastic activities. Upon intradermal administration, multi-epitope anti-folate receptor peptide vaccine TPIV 200 may induce a cytotoxic T-lymphocyte (CTL) response against FR-alpha-overexpressing tumor cells. FR-alpha is a high-affinity folate-binding protein and a member of the folate receptor family; this receptor is overexpressed in various cancer cell types.
An orally bioavailable inhibitor of cell division cycle 7 (cell division cycle 7-related protein kinase; CDC7), with potential antineoplastic activity. Upon administration, TAK-931 binds to and inhibits CDC7; this prevents the initiation of DNA replication during mitosis, which causes cell cycle arrest and induces apoptosis. This inhibits cell growth in CDC7-overexpressing tumor cells. CDC7, a serine/threonine kinase and cell division cycle protein, is overexpressed in a variety of cancers and plays a key role in the activation of DNA replication and the regulation of cell cycle progression.
A small molecule inhibitor of ubiquitin-activating enzyme (UAE), with potential antineoplastic activity. UAE inhibitor TAK-243 binds to and inhibits UAE, which prevents both protein ubiquitination and subsequent protein degradation by the proteasome. This results in an excess of proteins in the cells and may lead to endoplasmic reticulum (ER) stress-mediated apoptosis. This inhibits tumor cell proliferation and survival. UAE, also called ubiquitin E1 enzyme (UBA1; E1), is more active in cancer cells than in normal, healthy cells.
An orally bioavailable inhibitor of the nuclear export protein exportin-1 (XPO1; chromosome region maintenance 1 protein homolog; CRM1), with potential antineoplastic and pro-apoptotic activities. Upon administration, XPO1 inhibitor SL-801 reversibly binds to the cargo binding site of XPO1, and prevents the XPO1-mediated nuclear export of cargo proteins, including tumor suppressor proteins (TSPs), such as p53, FOXO, p21, and p27, and leads to their selective accumulation in the nuclei of tumor cells. As a selective inhibitor of nuclear export (SINE), SL-801 restores the nuclear localization and function of TSPs, which leads to the induction of apoptosis in tumor cells. XPO1, the major export factor that transports proteins and RNA from the nucleus to the cytoplasm, is overexpressed in a variety of cancer cell types while minimally expressed in normal, healthy cells. The dysregulated export of TSPs into the cytoplasm prevents TSP-initiated apoptosis. XPO1 overexpression leads to uncontrolled tumor cell proliferation and is associated with poor prognosis.
A cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. Upon administration, CDK4/6 inhibitor SHR6390 selectively inhibits cyclin-dependent kinase 4 (CDK4) and 6 (CDK6). This inhibits retinoblastoma (Rb) protein phosphorylation early in the G1 phase, which prevents CDK-mediated G1-S phase transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of cell cycle progression.
An orally bioavailable androgen receptor (AR) antagonist with potential antineoplastic activity. Upon administration, SHR3680 competitively binds to AR in target tissues, which both prevents androgen-induced receptor activation and facilitates the formation of inactive complexes that cannot be translocated to the nucleus. This prevents binding to and transcription of AR-responsive genes, inhibits the expression of genes that regulate prostate cancer cell proliferation, and may lead to an inhibition of cell growth of AR-expressing tumor cells. ARs are overexpressed in prostate cancer and play a key role in prostate cancer cell proliferation.
An antibody-drug conjugate (ADC) consisting of an anti-CD19 humanized monoclonal antibody (hBU12ec) with engineered cysteines (EC-mAb) conjugated, via a maleimidocaproyl-valine-alanine dipeptide protease-cleavable linker, to the cytotoxic, DNA minor-groove crosslinking agent pyrrolobenzodiazepine (PBD) dimer (SGD-1882), with potential antineoplastic activity. Upon administration of anti-CD19 ADC SGN-CD19B, the antibody moiety targets the cell surface antigen CD19, which is found on B-cell-derived cancers. Upon antibody/antigen binding, internalization and lysosome uptake, the cytotoxic PBD moiety is released. In turn, the imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces DNA strand breaks, inhibits DNA replication, leads to G2/M cell cycle arrest, induces cell death, and inhibits the proliferation of CD19-overexpressing tumor cells. CD19, a transmembrane receptor belonging to the immunoglobulin superfamily and a B-cell specific antigen, is expressed on B-cell-derived cancers. The cysteine engineering of the EC-mAb allows for a site-specific and stable conjugation of PBD to the antibody.
A synthetic copolymer-drug conjugate of a fumagillin-derived methionine aminopeptidase 2 (MetAP2) inhibitor conjugated to the bio-compatible polymer poly(N-(hydroxypropyl)methacrylamide) (HPMA), with potential antineoplastic activity. Upon administration of SDX-7320, the active moiety SDX7539 is released inside the tumor cells. SDX7539 binds to and inhibits MetAP2, which prevents MetAP2-mediated signal transduction pathways and results in tumor cell death. MetAP2, a member of the dimetallohydrolase family upregulated in certain tumor cell types, plays a key role in angiogenesis, proliferation and survival. Polymer conjugation reduces systemic drug exposure and increases this agent's efficacy as compared to non-polymer conjugates.
An antibody-drug conjugate (ADC) consisting of a monoclonal antibody against lysosome-associated membrane protein 1 (LAMP1) conjugated, via the disulfide-containing cleavable linker N-succinimidyl-4-(2-pyridyldithio)butyrate (SPDB), to the cytotoxic maytansinoid DM4, with potential antineoplastic activity. Upon administration of anti-LAMP1 ADC SAR428926, the anti-LAMP1 monoclonal antibody moiety targets and binds to the cell surface antigen LAMP1. After antibody-antigen interaction and internalization, the SPDB linker is selectively cleaved by proteases in the cytosol and the DM4 moiety is released. DM4 binds to tubulin and disrupts microtubule assembly/disassembly dynamics, thereby inhibiting both cell division and cell growth of LAMP1-expressing tumor cells. LAMP1, overexpressed on a variety of cancer cells, plays a key role in cell-cell adhesion and migration. The SPDB linker is resistant to cleavage in the bloodstream, which may increase stability and reduce toxicity.
A proprietary formulation containing a highly purified form of Staphylococcal protein A (SpA; protein A), with potential immunomodulating activity. Upon administration of PRTX-100, this protein is able to specifically bind to both the subset of B-lymphocytes that express the heavy chain variable region 3 (VH3)-encoded immunoglobulin (Ig) (VH3-B-cells) and macrophages. This prevents B-cell activation, induces apoptosis, prevents VH3-derived antibody formation, antibody-mediated immune responses, and destruction by macrophages. This may modulate specific immune signaling pathways and restore normal immune system functions caused by certain immune-mediated inflammatory diseases. In patients with the autoimmune-mediated disease immune thrombocytopenia (ITP), PRTX-100 prevents destruction of platelets, increases platelet production and platelet blood levels, and decreases the risk of bleeding. SpA, a 42 kDa bacterial membrane protein produced by Staphylococcus aureus bacteria, consists of five nearly identical Ig binding domains; each SpA domain binds with high affinity to the Igs containing regions encoded by the VH3 gene family. B-lymphocytes that express VH3-encoded Igs are specifically involved in various auto-immune diseases.
An inhibitor of the bromodomain-containing protein 4 (BRD4), with potential antineoplastic activity. Upon administration, the BRD4 inhibitor PLX51107 binds to the acetylated lysine recognition motifs in the bromodomains of the BRD4 protein, thereby preventing the binding of BRD4 to acetylated lysines on histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an induction of apoptosis and an inhibition of proliferation in BRD4-overexpressing tumor cells. BRD4, a member of the human bromodomain and extra-terminal (BET) family of proteins, is a transcriptional regulator that is overexpressed in certain tumor cells and plays an important role in cellular proliferation.
An orally available hydroxyamidine and inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with potential immunomodulating and antineoplastic activities. Upon administration, IDO1 inhibitor PF-06840003 targets and binds to IDO1, an enzyme responsible for the oxidation of tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, PF-06840003 increases and restores the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes; PF-06840003 also induces increased interferon (IFN) production, and causes a reduction in tumor-associated regulatory T cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may inhibit the growth of IDO1-expressing tumor cells. IDO1, a cytosolic enzyme responsible for tryptophan catabolism and the conversion of tryptophan into kynurenine, is overexpressed by a variety of tumor cell types and antigen presenting cells (APCs); it plays an important role in immunosuppression. Tryptophan depletion inhibits T-lymphocyte proliferation and activation, and subsequently suppresses the immune system.
A suspension-based oral spray containing multilamellar lipid vesicles in which the lipids mimic the lipidic composition of endogenous extra-alveolar lamellar bodies, with muco-restorative and protective activity against radiotherapy (RT)-induced xerostomia (RIX). Upon sublingual administration of the lamellar body mimetic LMS-611 using a spray, the lipids in this agent mimic the natural secretions of endogenous lamellar bodies. This makes mucus more fluid and may prevent dryness of the mouth. This restores saliva functions and makes it easier to chew, swallow and talk, and also prevents xerostomia-induced infections, tooth decay and tooth enamel decay. RT decreases saliva secretion by causing the destruction of the parotid and submandibular serous salivary glands and lamellar bodies. This results in thicker and more visco-adhesive saliva, which causes various xerostomia-induced symptoms; intact lamellar bodies maintain the fluidity of mucus and lubricate the mouth.
A multi-targeted agent with potential antineoplastic activity. Upon administration, NEV-801 appears to selectively inhibit topoisomerase (Topo) I and II, and activates hypoxia-inducible factor 1 (HIF-1) transcription and the expression of vascular endothelial growth factor (VEGF) mRNA. NEV-801 is also able to overcome multidrug resistance (MDR) 1-mediated resistance.
An agent that downregulates the activity of the anti-inflammatory cytokine human interleukin-10 (IL-10), with potential immunomodulating and antineoplastic activities. Upon administration, IL-10 immunomodulator MK-1966 blocks the activity of IL-10 and may abrogate the IL-10-induced immunosuppressive tumor microenvironment. This activates cell-mediated immunity against cancer cells, increases cytokine production, including interferon-gamma (IFN-g), decreases T regulatory cell (Treg) activity, and induces a tumor-specific cytotoxic CD8+ T-cell-mediated immune response, which enhances tumor cell death.
A synthetic, cyclic dinucleotide (CDN) and agonist of stimulator of interferon genes protein (STING; transmembrane protein 173; TMEM173), with potential immunomodulating and antineoplastic activities. Upon intratumoral administration, the STING agonist MIW815 binds to STING and stimulates STING-mediated pathways. This activates the immune response through the activation of certain immune cells, including dendritic cells (DCs), which induces the expression of cytokines and chemokines, and leads to an antigen-specific T-cell mediated immune response against cancer cells. STING, a transmembrane protein that activates immune cells in the tumor microenvironment, plays a key role in the activation of the innate immune system.
A microparticle combining two immune-modifying components derived from the bacterium Propionibacterium acnes, a bacterial cell wall component that is rich in muramyl dipeptide (MDP) and single-stranded bacteria-derived DNA fragments, with potential immunomodulating and immunoadjuvant activities. Upon administration of MIS416, this agent localizes in and is taken up mainly by the liver, thereby forming a liver depot. MIS416 is then taken up by immune cells, such as monocytes and dendritic cells (DCs), where MDP and the bacterial DNA target and bind to the cytosolic innate pattern recognition receptors (PRRs) nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and toll-like receptor 9 (TLR9), respectively. The simultaneous binding and activation of both NOD2 and TLR9, leads to activation of both NOD2 and TLR9 signaling. This stimulates the innate immune system, induces secretion of cytokines, particularly interferon (IFN), and modulates the activation of various immune cells. In the presence of tumor-associated antigens (TAAs), through simultaneous administration of a TAA-based vaccine, MIS416 modulates T-cell subsets and enhances the cytotoxic T lymphocyte (CTL)-mediated immune response against TAAs, resulting in an increased anti-tumor immune response. The combination of NOD2 and TLR9 agonists in MIS416 appears to activate different signaling pathways as compared to the administration of NOD2 and TLR9 agonists alone.
An antibody-drug conjugate (ADC) composed of a bispecific antibody against the extracellular domain of human epidermal growth factor receptor 2 (HER2; ERBB2) comprised of the single-chain variable fragment (scFv) of the anti- HER2 monoclonal antibody trastuzumab, which binds to domain IV of HER2, fused to the heavy chains of the anti-HER2 monoclonal antibody 39S, which binds to domain II of HER2, and conjugated, via a cleavable linker, to the cytotoxic anti-microtubule agent tubulysin, with potential antineoplastic activity. Upon administration of ADC MEDI4276, the anti-HER2 bispecific antibody specifically targets and binds to HER2 on the surface of certain cancer cells. Upon binding, crosslinking and internalization of antibody-HER2 complexes occurs and MEDI4276 is transported to the lysosome where the linker is cleaved, thereby delivering tubulysin inside HER2-expressing cancer cells. Tubulysin binds to tubulin and inhibits microtubule polymerization, which blocks cell division. This results in G2/M phase arrest, tumor cell apoptosis, and decreased proliferation of HER2-expressing tumor cells. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types.
A synthetic conjugate composed of the bisphosphonate etidronate linked to the cytostatic agent and antimetabolite cytarabine, with potential antineoplastic and antiresorptive activities. Upon intravenous administration of the etidronate-cytarabine conjugate MBC-11, the etidronate moiety targets bone and the two moieties are released upon hydrolysis. Etidronate binds to hydroxyapatite crystals in bone tissues and prevents its resorption. This prevents bone destruction and induces bone cell mineralization. In addition, the bone-targeting nature of this agent allows for the accumulation of cytarabine in bone tissue, where it is able to exert its antitumor effect locally by competing with cytidine for incorporation into DNA, thereby inhibiting DNA synthesis, while reducing systemic exposure. This leads to a destruction of bone-associated tumor cells, an inhibition of tumor cell proliferation and bone metastasis, and prevents tumor-mediated bone destruction.
An orally available inhibitor of extracellular signal-regulated kinase (ERK), with potential antineoplastic activity. Upon oral administration, LTT462 binds to and inhibits ERK, thereby preventing the activation of ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent tumor cell proliferation and survival. The mitogen-activated protein kinase (MAPK)/ERK pathway is upregulated in numerous tumor cell types and plays a key role in tumor cell proliferation, differentiation and survival.
An selective estrogen receptor (ER) degrader (SERD), with potential antineoplastic activity. Upon administration of LSZ102, this agent binds to the ER and induces the degradation of the receptor. This prevents ER activation and ER-mediated signaling, and inhibits the growth and survival of ER-expressing cancer cells.
An indenoisoquinoline derivative and topoisomerase 1 (Top1) inhibitor, with potential antineoplastic activity. Upon administration, LMP744 binds to and stabilizes cleaved DNA-Top1 complexes, which prevents DNA re-ligation, induces stable, irreversible DNA strand breaks, prevents DNA repair, and leads to cell cycle arrest and apoptosis. As tumor cells proliferate at a much higher rate than normal cells, LMP744 specifically targets cancer cells. Top1, a DNA modifying enzyme essential for transcription, replication, and repair of double-strand DNA breaks, is overexpressed in tumor cells.
An anti-mesothelin (MSLN) recombinant cytolytic fusion protein (cFP) composed of a humanized Fab fragment of anti-MSLN monoclonal antibody SS1 linked to a truncated and de-immunized 24 kDa fragment of the Pseudomonas exotoxin (PE) (PE24), with potential antineoplastic activity. Upon intravenous administration of anti-MSLN-PE24 cFP LMB-100, the anti-MSLN moiety targets and binds to MSLN-expressing tumor cells. Upon binding and internalization through endocytosis, the toxin moiety ADP-ribosylates and inactivates eukaryotic elongation factor 2 (eEF2), preventing the elongation step of protein synthesis and leading to both an inhibition of protein synthesis and an induction of MSLN-expressing tumor cell apoptosis. MSLN, a tumor-associated antigen overexpressed in a variety of cancer cell types, plays a key role in tumor cell proliferation and migration. The engineered PE24 portion of LMB-100 does contain the targeting domain and furin cleavage site, which are needed for cytotoxicity, but most of the translocation domain II is deleted and the catalytic domain III contains point mutations, which result in the deletion and silencing of most T- and B-cell epitopes; therefore, the immunogenicity and toxicity is reduced compared to non-engineered PE toxin, which allows for the administration of larger doses of LMB-100.
An orally bioavailable inhibitor of both the serine/threonine kinase P21-activated kinase 4 (PAK4) and the nicotinamide adenine dinucleotide (NAD)-synthesizing enzyme nicotinamide phosphoribosyltransferase (NAMPT; NAMPRTase), with potential antineoplastic activity. Upon administration, KPT-9274 allosterically binds to, destabilizes and causes degradation of PAK4. This inhibits PAK4-mediated signaling, induces cell death in, and inhibits the proliferation of PAK4-overexpressing tumor cells. In addition, KPT-9274 binds to and inhibits the activity of NAMPT. This depletes cellular NAD and inhibits NAD-dependent enzymes, both of which are needed for rapid cell proliferation; this results in tumor cell death in NAMPT-overexpressing cancer cells. PAK4, a serine/threonine kinase and member of the PAK family of proteins upregulated in various cancer cell types, regulates cell motility, proliferation and survival. NAMPT, an enzyme that is responsible for maintaining the intracellular NAD pool, plays a key role in the regulation of cellular metabolism and has cytokine-like activities. NAMPT is often overexpressed in a variety of cancers and metabolic disorders and tumor cells rely on NAMPT activity for their NAD supply.
A dual selective inhibitor of the beta and delta isoforms of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinase (PI3K-beta/delta), with potential antineoplastic activity. PI3K-beta/delta inhibitor KA2237 selectively inhibits the PI3K-beta and -delta isoforms and prevents their activation, which inhibits PI3K-beta/delta-mediated signal transduction pathways. This decreases proliferation and induces cell death in susceptible tumor cells. Unlike other isoforms of PI3K, PI3K-beta and -delta are overexpressed primarily in solid and hematological tumor cells and play crucial roles in tumor cell survival, and immunoregulation. The targeted inhibition of these PI3Ks allows this agent to potentially be more efficacious and less toxic than pan PI3K inhibitors, which also affect normal, healthy cells.
A humanized anti-CD123/anti-CD3 bispecific monoclonal antibody, with potential immunostimulating and antineoplastic activities. Anti-CD123/CD3 bispecific antibody JNJ-63709178 possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for CD123, a tumor-associated antigen (TAA) overexpressed on the surface of certain tumor cells. Upon administration of JNJ-63709178, this bispecific antibody simultaneously binds to both CD3-expressing T-cells and CD123-expressing cancer cells, thereby crosslinking CD123-expressing tumor cells and cytotoxic T-lymphocytes (CTLs). This may result in potent CTL-mediated cell lysis of CD123-expressing tumor cells. CD123, the interleukin-3 receptor alpha chain, is overexpressed in a variety of cancers; its expression is low or absent in normal, healthy cells.
An orally available inhibitor of lysine-specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, INCB059872 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4, respectively, through amine oxidation. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes. Altogether, this may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, an enzyme belonging to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family, is overexpressed in certain tumor cells and plays a key role in the regulation of gene expression and in tumor cell growth and survival.
An inhibitor of the Bromodomain (BRD) and Extra-Terminal (BET) family of BRD-containing proteins, with potential antineoplastic activity. Upon administration, the BET inhibitor INCB057643 binds to the acetylated lysine recognition motifs found in the BRD of BET proteins, thereby preventing the interaction between the BET proteins and acetylated lysines on histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes, such as c-Myc-dependent target genes, may lead to an inhibition of tumor cell growth. BET proteins are transcriptional regulators that are overexpressed in certain tumor cells and play an important role in cellular growth.
An anti-human glucocorticoid-induced tumor necrosis factor receptor (tumor necrosis factor superfamily, member 18; TNFRSF18; GITR; CD357) agonistic humanized monoclonal antibody, with potential immune checkpoint modulating activity. Anti-GITR antibody INCAGN01876 binds to and activates GITRs found on multiple types of T-cells. This stimulates the immune system, induces both the activation and proliferation of tumor-antigen-specific T effector cells (Teff), and suppresses the function of activated T regulatory cells (Tregs). This leads to tumor cell eradication. GITR, a member of the TNF receptor superfamily and T-cell receptor co-stimulator, is expressed on the surface of multiple immune cell types, including Tregs, Teffs, B-cells, and natural killer (NK) cells. Inappropriately activated Tregs suppress Teffs and suppress T-cell receptor (TCR) signaling.
A cancer vaccine consisting of a fusion peptide, composed of three peptides derived from the extracellular domain (ECD) of the HER2 peptide antigen found on B-cells (P4, P6 and P7; P467), conjugated to the carrier protein DT-CRM197, a non-toxic, mutated form of diphtheria toxin (DT), and combined with the immunoadjuvant montanide ISA 51, with potential immunostimulatory and antineoplastic activities. Upon administration, IMU-131 vaccine induces the production of polyclonal antibodies against the HER2 protein. In turn, the antibodies bind to three separate binding sites on HER2 expressed on tumor cells and inhibit HER2 dimerization and activity, which leads to the inhibition of HER2-mediated signal transduction pathways. This induces apoptosis in and reduces cellular proliferation of HER2-overexpressing tumor cells. In addition, IMU-131 induces a cytotoxic T-lymphocyte (CTL) response against the HER2-expressing tumor cells. The tumor-associated antigen (TAA) HER2, also called Neu or ErbB2, is a tyrosine kinase receptor for epidermal growth factor (EGF) and is often overexpressed by a variety of tumor cell types. Montanide ISA 51, also known as incomplete Freund's adjuvant or IFA, is a stabilized water-in-oil (w/o) emulsion adjuvant containing mineral oil with mannide oleate added as a surfactant that non-specifically stimulates cell-mediated immune responses to antigens. DT-CRM197 is used to increase the immunogenicity of the HER2/neu peptide antigen. In P467, the three B-cell epitopes were combined in a specific order into a single 49 amino acid peptide antigen.
An orally bioavailable inhibitor of human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon administration, H3B-6527 specifically binds to and blocks FGFR4. This prevents the activation of FGFR4, inhibits FGFR4-mediated signaling and leads to an inhibition of cell proliferation in FGFR4-overexpressing tumor cells. FGFR4, a receptor tyrosine kinase overexpressed by certain tumor cell types, is involved in tumor cell proliferation, differentiation, angiogenesis, and survival; FGFR4 expression is associated with poor prognosis.
An anti-human glucocorticoid-induced tumor necrosis factor receptor (tumor necrosis factor superfamily, member 18; TNFRSF18; GITR; CD357) agonistic monoclonal antibody, with potential immune checkpoint modulating activity. Anti-GITR antibody GWN 323 binds to and activates GITRs found on multiple types of T-cells. This stimulates the immune system, induces both the activation and proliferation of tumor-antigen-specific T effector cells (Teff), and suppresses the function of activated T regulatory cells (Tregs). This leads to tumor cell eradication. GITR, a member of the TNF receptor superfamily and T-cell receptor co-stimulator, is expressed on the surface of multiple immune cell types, including Tregs, Teffs, B-cells, and natural killer (NK) cells. Inappropriately activated Tregs suppress both Teffs and T-cell receptor (TCR) signaling.
An agonistic antibody for the inducible T-cell co-stimulator (ICOS; CD278), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-ICOS agonist antibody GSK3359609 targets and binds to ICOS expressed on tumor infiltrating CD4-positive T-cells. This stimulates ICOS-positive T-cell proliferation, enhances cytotoxic T-lymphocyte (CTL) survival and increases CTL-mediated immune responses against tumor cells. ICOS, a T-cell specific, CD28-superfamily costimulatory molecule and immune checkpoint protein, is normally expressed on certain activated T-cells and plays a key role in the proliferation and activation of T-cells.
A toll-like receptor 4 (TLR4) agonist, with potential immunoadjuvant activity. Upon administration, GSK1795091 binds to and activates TLR4, thereby stimulating dendritic cells (DCs), monocytes and macrophages. This activation results in the production of pro-inflammatory cytokines, including interferon gamma (IFN-g), tumor necrosis factor-alpha (TNF-a) and the interleukins (IL), IL-1 beta, -6 and -12. This may induce a T helper cell-1 (Th1) immune response and, upon co-administration of a vaccine containing tumor-associated antigens (TAAs), activates a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing those TAAs. TLR4, a member of the TLR family, plays a key role in the activation of innate immunity.
An orally bioavailable inhibitor of the Bromodomain and Extra-Terminal (BET) family of proteins, with potential antineoplastic activity. Upon oral administration, the BET inhibitor GS-5829 binds to the acetylated lysine recognition motifs in the bromodomains of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of proliferation in BET-overexpressing tumor cells. BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.
A cancer peptide vaccine composed of four human leukocyte antigen (HLA)-A2 (HLA-A*02)-restricted peptides derived from four specific and separate tumor-associated antigens (TAAs) expressed by melanoma cells, with potential antineoplastic activity. Upon administration of the HLA-A2-restricted melanoma-specific peptides vaccine, the melanoma specific antigens in the vaccine activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against the HLA-A2-positive melanoma cells.
A cytotoxic recombinant fusion protein consisting of the human cytokine interleukin-2 (IL-2) fused to diphtheria toxin fragments A and B, containing both the catalytic and translocation domains, with potential antineoplastic activity. Upon administration, the IL-2 moiety of diphtheria toxin fragment-IL-2 fusion protein E7777 binds to IL-2 receptors. After internalization by IL-2 receptor-expressing cells via endocytosis, the agent is proteolytically cleaved. This releases the catalytic domain of the toxin moiety, which catalyzes the transfer of the ADP-ribose moiety of NAD to a diphthamide residue of elongation factor 2 (EF-2). This covalent modification inactivates EF-2 and disrupts polypeptide chain elongation, resulting in an inhibition of translation and cell death. E7777 has the same amino acid sequence as denileukin diftitox (DD), but has an increased purity profile and an increased percentage of monomeric, active protein, which improves its efficacy.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (ERBB2; EGFR2; HER2) conjugated to a derivative of the camptothecin analog exatecan (DXd; DX-8951 derivative), a DNA topoisomerase 1 (topoisomerase I; Top1) inhibitor, with potential antineoplastic activity. Upon administration of anti-HER2 ADC conjugate DS-8201a, the antibody moiety targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, the DX-8951 derivative moiety binds to and inhibits Top1-DNA complexes, which results in an inhibition of DNA replication, cell cycle arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. In addition, DS-8201a induces antibody-dependent cell-mediated cytotoxicity (ADCC) and causes a bystander killing effect, thereby killing neighboring HER2-expressing tumor cells.
An orally available selective inhibitor of the histone lysine methyltransferases enhancer of zeste homolog 1 (EZH1) and 2 (EZH2), with potential antineoplastic activity. Upon oral administration, DS-3201 selectively inhibits the activity of both wild-type and mutated forms of EZH1 and EZH2. Inhibition of EZH1/2 specifically prevents the methylation of lysine 27 on histone H3 (H3K27). This decrease in histone methylation alters gene expression patterns associated with cancer pathways, enhances transcription of certain target genes, and results in decreased proliferation of EZH1/2-expressing cancer cells. EZH1/2, histone lysine methyltransferase (HMT) class enzymes and catalytic subunits of the polycomb repressive complex 2 (PRC2), are overexpressed or mutated in a variety of cancer cells and play key roles in tumor cell proliferation, progression, stem cell self-renewal and migration.
An orally available inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), with potential antineoplastic activity. Upon administration, ALK/FAK/Pyk2 inhibitor CT-707 selectively binds to and inhibits ALK , FAK and Pyk2. The inhibition leads to disruption of ALK- , FAK- and Pyk2-mediated signal transduction pathways and eventually inhibits tumor cell growth in ALK-, FAK- and Pyk2-overexpressing tumor cells. Expression of these tyrosine kinases is dysregulated in various tumor types; they play a key role in tumor cell migration, proliferation, survival, and tumor angiogenesis.
An orally available antagonist of the glucocorticoid receptor (GR), with potential antineoplastic activity. Upon administration, CORT125134 competitively binds to and blocks GRs. This inhibits the activity of GRs, and prevents both the translocation of the ligand-GR complexes to the nucleus and gene expression of GR-associated genes. This decreases the negative effects that result from excess levels of endogenous glucocorticoids, like those seen when tumors overproduce glucocorticoids. In addition, by binding to GRs and preventing their activity, inhibition with CORT125134 also inhibits the proliferation of GR-overexpressing cancer cells. GRs are overexpressed in certain tumor cell types and promote tumor cell proliferation.
An agent composed of an unmethylated CpG motif-rich G10 oligonucleotide, which is an agonist of toll-like receptor 9 (TLR9), encapsulated in noninfectious virus-like particles (VLPs), with potential immunostimulating and antineoplastic activities. Upon administration of CMP-001, the VLPs are specifically taken up by and release the oligonucleotide into antigen-presenting cells (APCs), including dendritic cells (DCs). In turn, the oligonucleotide binds to and activates intracellular TLR9. This stimulates immune signaling pathways, induces the innate immune system and may promote the immune system to attack tumor cells. VLPs stimulate the immune system. TLR9, a member of the TLR family, plays a key role in both pathogen recognition and the activation of innate immunity.
A preparation of autologous T-lymphocytes expressing a chimeric antigen receptor (CAR) consisting of an anti-human prostate stem cell antigen (PSCA) scFv (single chain variable fragment) coupled to the zeta chain of the T-cell receptor (TCRzeta) and a drug-induced co-stimulatory molecule, composed of an inducible, chimeric MyD88/CD40 (inducible MC; iMC) co-stimulatory domain, in which both the MyD88 and CD40 lack their extracellular domains, with potential antineoplastic activity. Upon administration of BPX-601, the T-cells target and bind to PSCA-expressing cancer cells. Upon subsequent administration of the chemical inducer of dimerization (CID) agent rimiducid, this agent targets and binds to the drug binding domain, which leads to iMC expression, activation of both CD40- and MyD88-mediated signal transduction pathways, and an induction of selective cytotoxicity in, and eradication of PSCA-expressing cancer cells. iMC activation by rimiducid increases T-cell survival and anti-tumor activity of the administered T-cells, compared to T-cells without the drug iMC activation-switch. As these T-cells are engineered to only be fully activated by binding to both antigen and rimiducid, T-cell proliferation, activity and toxicity can be controlled by adjusting the dose of rimiducid, thereby preventing uncontrolled T-cell activation which increases the safety of the administered T-cells. PSCA is a glycosylphosphatidylinositol (GPI)-anchored cell surface antigen overexpressed in many cancer cell types.
An agonistic monoclonal antibody against the co-stimulatory receptor OX40 (CD134; TNFRSF4), with potential immunostimulatory activity. Upon administration, anti-OX40 monoclonal antibody BMS 986178 selectively binds to and activates the OX40 receptor, by mimicking the action of the endogenous OX40 ligand (OX40L). OX40 receptor activation induces proliferation of memory and effector T-lymphocytes. In the presence of tumor-associated antigens (TAAs), this may promote an immune response against the TAA-expressing tumor cells. OX40, a cell surface glycoprotein and member of the tumor necrosis factor receptor family (TNFRSF), is expressed on T-lymphocytes and provides a co-stimulatory signal for the proliferation and survival of activated T-cells.
A nanobody directed against angiopoietin-2 (Ang2; ANGPT2)- and vascular endothelial growth factor (VEGF)-derived peptides, with potential antiangiogenic and antineoplastic activities. Anti-VEGF/ANG2 nanobody BI 836880 binds to Ang2 and VEGF and inhibits receptor binding; this prevents Ang2- and VEGF-mediated signaling and inhibits both tumor angiogenesis and tumor cell proliferation. Both VEGF and Ang2 are upregulated in a variety of cancer cell types and play a crucial role in angiogenesis. The nanobody is based on functional fragments of single-chain antibodies.
An inhibitor of cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the RNA polymerase II (RNA Pol II) elongation factor positive transcription elongation factor b (PTEF- b; PTEFb), with potential antineoplastic activity. Upon administration, BAY1251152 binds to and blocks the phosphorylation and kinase activity of CDK9, thereby preventing PTEFb-mediated activation of RNA Pol II and leading to the inhibition of gene transcription of various anti-apoptotic proteins. This may cause cell cycle arrest and induce apoptosis, which may lead to a reduction in tumor cell proliferation. The protein complex PTEF-b, a heterodimer consisting of CDK9 and a regulatory cyclin subunit of the T family, is over-activated in various tumor cell types; it plays a key role in the regulation of Pol II-mediated transcription of anti-apoptotic proteins. Tumor cells are dependent on anti-apoptotic proteins for their survival.
An orally available inhibitor of specific mutant forms of both human epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2; ERBB2), with potential antineoplastic activity. Upon oral administration, EGFR/HER2 inhibitor AP32788 specifically and irreversibly binds to and inhibits certain mutant forms of EGFR and HER2. This prevents EGFR- and HER2-mediated signaling and leads to cell death in EGFR mutant- and HER2 mutant-expressing tumor cells. EGFR and HER2, receptor tyrosine kinases mutated in many tumor cell types, play key roles in tumor cell proliferation and tumor vascularization.
A selective effector cell activator protein and agonist of the intermediate-affinity interleukin-2 (IL-2) receptor with potential immunostimulating and antineoplastic activity. Upon administration, intermediate-affinity interleukin-2 receptor agonist ALKS 4230 binds to and signals through the intermediate-affinity IL-2 receptor complex; this may selectively stimulate and activate natural killer (NK) cells and memory CD8 T-cells, leading to tumor cell elimination, while circumventing the activation of immunosuppressive cells that may prevent the anti-tumor response. IL-2 is a cytokine signaling molecule that plays a critical role in the immune response.
An orally bioavailable small molecule inhibitor of the oncoprotein c-Met (hepatocyte growth factor receptor; HGFR), with potential antineoplastic activity. Upon oral administration AL2846 targets and binds to the c-Met protein, prevents c-Met phosphorylation and disrupts c-Met-dependent signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.
A recombinant human monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), with immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-CTLA-4 monoclonal antibody AGEN1884 binds to CTLA-4 expressed on T-cells and inhibits the CTLA-4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA-4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system.
A human monoclonal antibody against the carbohydrate antigen sialyl-Lewis A (carbohydrate antigen 19-9; CA19-9), with potential antineoplastic activity. Upon administration, monoclonal antibody 5B1 binds to CA19-9 and kills CA19-9-expressing tumor cells, possibly through the induction of both complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). CA19-9 is overexpressed on a number of different tumor cell types, and plays a key role in tumor cell survival and metastasis.
A human, Fc-optimized, immunoglobulin G1 (IgG1) monoclonal antibody directed against the FLT3 tyrosine kinase receptor (CD135), with potential antineoplastic activity. Upon binding to FLT3, anti-FLT3 monoclonal antibody 4G8-SDIEM blocks FLT3 ligand binding to FLT3 and subsequent phosphorylation of FLT3, which may result in the inhibition of FLT3-mediated signal transduction pathways. In addition, this agent may stimulate an anti-FLT3 antibody-dependent cell-mediated cytotoxicity (ADCC) against FLT3-expressing tumor cells, which may lead to the inhibition of cellular proliferation and decreased survival in FLT3-expressing cells. FLT3 (FLK2), a class III tyrosine kinase receptor, is overexpressed or mutated in most B lineage and acute myeloid leukemias.
A polyethylene glycol (PEG) conjugate of 7-ethyl-10-hydroxycamptothecin with potential antineoplastic activity. After hydrolysis in vivo, 7-ethyl-10-hydroxycamptothecin (SN38), an active metabolite of irinotecan, is released from firtecan pegol; 7-ethyl-10-hydroxycamptothecin selectively stabilizes topoisomerase I-DNA covalent complexes, resulting in single-stranded and double-stranded DNA breaks, the inhibition of DNA replication, and the induction of apoptosis. This agent is designed to deliver the active metabolite to tumor cells without the need for conversion as is the case with irinotecan. Compared to unPEGylated 7-ethyl-10-hydroxycamptothecin, PEGylation improves solubility and allows for parental delivery, and may result in a longer half-life and higher exposure for tumor cells.
A humanized monoclonal antibody directed against the human chemokine receptor 2 (CCR2), with potential antiangiogenic, immunomodulating, antimetastatic, and antineoplastic activities. Plozalizumab binds to CCR2 and prevents binding of the endothelium-derived CLL2 (monocyte chemoattractant protein-1 or MCP1) to its receptor CCR2, which may result in inhibition of CCR2 activation and so inhibition of angiogenesis, tumor cell migration, and tumor cell proliferation. In addition, this agent may reduce levels of C-reactive protein (CRP). The G-protein coupled receptor CCR2 is expressed on the surface of monocytes and macrophages, stimulates the migration and infiltration of these cell types, and plays an important role in inflammation, angiogenesis, and tumor cell migration and proliferation.
An inhibitor of MET tyrosine kinase with potential antineoplastic activity. Tepotinib selectively binds to MET tyrosine kinase and disrupts MET signal transduction pathways, which may induce apoptosis in tumor cells overexpressing this kinase. The receptor tyrosine kinase MET (also known as hepatocyte growth factor receptor or HGFR), is the product of the proto-oncogene c-Met and is overexpressed or mutated in many tumor cell types; this protein plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis.
The hydrochloride salt form of defactinib, an orally bioavailable, small-molecule focal adhesion kinase (FAK) inhibitor with potential antiangiogenic and antineoplastic activities. Defactinib inhibits FAK, which may prevent the integrin-mediated activation of several downstream signal transduction pathways, including those involving RAS/MEK/ERK and PI3K/Akt, thus inhibiting tumor cell migration, proliferation, survival, and tumor angiogenesis. The tyrosine kinase FAK, a signal transducer for integrins, is normally activated by binding to integrins in the extracellular matrix (ECM) but may be upregulated and constitutively activated in various tumor cell types.
An orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. Vistusertib inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, plays an important role downstream in the PI3K/Akt/mTOR signaling pathway.
A capsule formulation containing a small-molecule receptor tyrosine kinase (RTK) inhibitor of KIT, CSF1R and FLT3 with potential antineoplastic activity. Pexidartinib binds to and inhibits phosphorylation of stem cell factor receptor (KIT), colony-stimulating factor-1 receptor (CSF1R) and FMS-like tyrosine kinase 3 (FLT3), which may result in the inhibition of tumor cell proliferation and down-modulation of macrophages, osteoclasts and mast cells involved in the osteolytic metastatic disease. FLT3, CSF1R and FLT3 are overexpressed or mutated in many cancer cell types and play major roles in tumor cell proliferation and metastasis.
An orally available, small molecule inhibitor of the proto-oncogene c-Met (also known as hepatocyte growth factor receptor (HGFR)) with potential antineoplastic activity. Merestinib selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. This agent has potent anti-tumor efficacy in mono and combination therapy in a broad range of cancers. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.
An inhibitor of checkpoint kinase 1 (chk1) with potential antineoplastic activity. Upon administration, prexasertib selectively binds to chk1, thereby preventing activity of chk1 and abrogating the repair of damaged DNA. This may lead to an accumulation of damaged DNA and may promote genomic instability and apoptosis. Prexasertib may potentiate the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapeutic agents. Chk1, a serine/threonine kinase, mediates cell cycle checkpoint control and is essential for DNA repair and plays a key role in resistance to chemotherapeutic agents.
An orally bioavailable, selective inhibitor of Bruton's agammaglobulinemia tyrosine kinase (BTK), with potential antineoplastic activity. Upon administration, spebrutinib targets and covalently binds to BTK, thereby preventing its activity. By irreversibly inhibiting BTK, administration of this agent may lead to an inhibition of B cell receptor (BCR) signaling and may inhibit cell proliferation of B-cell malignancies. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
A lipid-permeable tacrolimus analogue with homodimerizing activity. Dimerizer drug AP1903 homodimerizes an analogue of human protein FKBP12 (Fv) which contains a single acid substitution (Phe36Val) so that AP1903 binds to wild-type FKBP12 with 1000-fold lower affinity. This agent is used to homodimerize the Fv-containing drug-binding domains of genetically engineered receptors such as the iCD40 receptor of the autologous dendritic cell vaccine BP-GMAX-CD1, resulting in receptor activation.
An orally available cancer cell stemness inhibitor with potential antineoplastic activity. Even though the exact target has yet to be fully elucidated, napabucasin appears to target and inhibit multiple pathways involved in cancer cell stemness. This may ultimately inhibit cancer stemness cell (CSC) growth as well as heterogeneous cancer cell growth. CSCs, self-replicating cells that are able to differentiate into heterogeneous cancer cells, appear to be responsible for the malignant growth, recurrence and resistance to conventional chemotherapies.
An orally available inhibitor of extracellular signal-regulated kinase (ERK) 1 and 2, with potential antineoplastic activity. Upon oral administration, BVD-523 inhibits both ERK 1 and 2, thereby preventing the activation of ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent tumor cell proliferation and survival. The mitogen-activated protein kinase (MAPK)/ERK pathway is often upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation, differentiation and survival.
A modulator of the E3 ubiquitin ligase complex containing cereblon (CRL4-CRBN E3 ubiquitin ligase), with immunomodulating and pro-apoptotic activities. Upon administration, iberdomide specifically binds to the cereblon (CRBN) part of the ligase complex, thereby affecting the ubiquitin E3 ligase activity, and targeting certain substrate proteins for ubiquitination. This induces the proteasome-mediated degradation of certain transcription factors, including Ikaros (IKZF1) and Aiolos (IKZF3) which are transcriptional repressors in T-cells. This leads to a reduction of their protein levels, and the modulation of the immune system, including activation of T-lymphocytes. In addition, this leads to a downregulation of other proteins, including interferon regulatory factor 4 (IRF4), which plays a key role in the proliferation of certain cancer cell types. CRBN, the substrate recognition component of the E3 ubiquitin ligase complex, plays a key role in the ubiquitination of certain proteins.
An orally available inhibitor of receptor tyrosine kinases anaplastic lymphoma kinase (ALK) and the epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Brigatinib binds to and inhibits ALK kinase and ALK fusion proteins as well as EGFR and mutant forms. This leads to the inhibition of ALK kinase and EGFR kinase, disrupts their signaling pathways and eventually inhibits tumor cell growth in susceptible tumor cells. In addition, AP26113 appears to overcome mutation-based resistance. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. EGFR is overexpressed in a variety of cancer cell types.
A category of staging terms for ovarian cancer according to the International Federation of Gynecology and Obstetrics (FIGO), 2014. AJCC ovarian cancer stage terms from the 6th and 7th editions that are synonymous to the FIGO ovarian cancer staging classification of 2014 are included as preferred terms.
A category of staging terms for ovarian cancer according to the American Joint Committee on cancer (AJCC) 6th and 7th editions. International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging terms prior to 2014 are included in this category if synonymous with the AJCC terms.
A cytogenetic abnormality that involves a translocation between chromosomes 11 and 14.
A malignant solid neoplasm that has spread from its original site of growth to another anatomic site.
The measurement of the average rate of blood flow across an area or tissue.
A nucleotide substitution at position 794 of the coding sequence of the MYD88 gene where thymine has been mutated to cytosine.
A response indicating that an individual experiences or experienced some shortness of breath.
A decrease by 50% for ALT, alkaline phosphatase, and total bilirubin.
Tuberculosis disease that is caused by a pre-extensively drug-resistant strain of Mycobacterium tuberculosis.
A subjective score of 3 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
An uncommon benign polypoid or nodular mesenchymal neoplasm that arises in the vulvovaginal region. It is characterized by the presence of oval or spindle-shaped cells in a collagenous stroma and is separated from the epidermis by a variably thick Grenz zone.
An extremely rare malignant mesenchymal neoplasm of the vulva exhibiting skeletal muscle differentiation with an alveolar pattern.
A benign lesion characterized by the presence of rounded, lobular aggregates of endocervical glands in the cervical wall.
A variation in the amino acid sequence for the fibroblast growth factor receptor 3 protein.
A finding of complete esophageal clearance following swallowing.
A score of 1+ on a comparative scale that ranges from 3+: Very much better to -3: Very much worse.
A variation in the amino acid sequence for the thrombopoietin receptor protein.
A condition of decreased or absent presence or activity of magnesium transporter 1 protein. Deficiency of this protein is associated with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (XMEN).
A score of 4 on the COXEN Sensitivity Scale.
A score of 30 on the COXEN Sensitivity Scale.
A score of 15 on the COXEN Sensitivity Scale.
A category of mesenchymal gynecologic neoplasms. It includes endometrial stromal nodule, endometrioid stromal sarcoma, and undifferentiated sarcoma. Endometrial stromal nodule has been described in the uterine corpus only. Histologically, it is characterized by the lack of infiltration of the surrounding tissues. Endometrioid stromal sarcoma affects the uterine corpus, and rarely, the ovaries, cervix, and vagina. In the uterine corpus it is classified as low grade or high grade endometrial stromal sarcoma. In the remainder of the anatomic sites it is classified as low grade endometrioid stromal sarcoma. Undifferentiated sarcoma was previously also known as high grade endometrial stromal sarcoma. In 2014, high grade endometrial stromal sarcoma was reclassified and is currently considered a distinct and rare neoplasm that affects the uterine corpus only. It appears to have a prognosis that falls between low grade endometrial stromal sarcoma and undifferentiated sarcoma. The latter affects the uterine corpus and rarely the remainder of the anatomic sites.
The direct transmission of an infectious agent to a host by a spray of a relatively large (greater than five microns), short range respiratory aerosol.
A subjective score of 1 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A response indicating that this is an individual's first visit to the clinic.
An immunohistochemical finding indicating the presence of growth hormone and prolactin producing cells in a tumor.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the gastroesophageal junction. It is characterized by the presence of malignant small cells.
A rare serous adenofibroma arising from the broad ligament.
A non-invasive clear cell adenofibromatous neoplasm that arises from the ovary. It is characterized by the presence of atypia in the glandular epithelium.
The integral of all of the flow velocities during the time of blood flow across or within a specified area.
Cervical metaplasia in which the cervical squamous epithelium resembles benign urothelium as a result of a lack of cellular maturation.
A qualitative assesment of the movement of the cardiac muscle, either as a whole or at one or more specific anatomical locations.
A change in the nucleotide sequence of the BRCA2 gene that is associated with increased risk of disease.
The maximum rate of the annular motion during early diastole (passive ventricular filling).
A change in the nucleotide sequence of the STK11 gene.
A subjective rating score of 3 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A finding of escape beyond the vermilion border during swallowing.
A constellation of findings in male mice characterized by ulceration and/or inflammation of the penis and prepuce, proteinaceous material with inflammatory cells, spermatozoa or desquamated urothelial cells forming a plug in the urethra and generally dilatation of the bladder, hydroureter and hydronephrosis.
The area of the vena contracta of the mitral valve.
A change in the amino acid residue at position 681 in the platelet-derived growth factor receptor beta protein where threonine has been replaced by isoleucine.
Any conservative mutation in the coding region of the TP53 gene that maintains the structure and function of the p53 protein.
A finding of no laryngeal vestibular closure; wide column air/contrast in laryngeal vestibule.
The indirect transmission of an infectious agent to a host via inanimate objects such as food, water, biologic products, or fomites.
A response indicating that an individual used a text message-based smoking cessation program to quit smoking cigarettes.
A change in the nucleotide sequence of the IDH1 or IDH2 gene.
A cytogenetic abnormality that involves a translocation between chromosomes 8 and 14.
A cytogenetic abnormality that involves a translocation between chromosomes 6 and 9.
A cytogenetic abnormality that involves a translocation between chromosomes 6 and 11.
A cytogenetic abnormality that refers to the translocation of the short arm (p16) of chromosome 4 and the long arm (q32) of chromosome 14.
A cytogenetic abnormality that involves a translocation between chromosomes 4 and 11.
A cytogenetic abnormality that involves a translocation occurring within chromosome 3.
A cytogenetic abnormality that involves a translocation between chromosomes 2 and 13.
A cytogenetic abnormality that involves a translocation between chromosomes 21 and 22.
A cytogenetic abnormality that involves a translocation between chromosomes 1 and 19.
A cytogenetic abnormality that involves a translocation between chromosomes 1 and 13.
A cytogenetic abnormality that involves a translocation occurring within chromosome 16.
A cytogenetic abnormality that involves a translocation between chromosomes 15 and 17.
A cytogenetic abnormality that involves a translocation between chromosomes 14 and 18.
A cytogenetic abnormality that involves a translocation between chromosomes 12 and 21.
A cytogenetic abnormality that involves a translocation between chromosomes 11 and 22.
A cytogenetic abnormality that refers to the translocation of the long arm (q22) of chromosome 10 and the short arm (p13) of chromosome 17. It results in an YWHAE-FAM22 fusion. It has been described in high grade endometrial stromal sarcomas and a subset of clear cell sarcomas of the kidney.
A combination of tobacco, lime, spices, vegetable dyes, and areca nut. It is typically chewed for its stimulant effects.
Expression of fusion protein YWHAE-FAM22 transcripts resulting from a t(10;17)(q22;p13). The translocation results in rearrangement of the YWHAE gene on chromosome 17 and FAM22 gene on chromosome 10. It has been described in high grade endometrial stromal sarcomas and a subset of clear cell sarcomas of the kidney.
A finding of a wide column of contrast or air between tongue base and posterior pharyngeal wall during swallowing.
A rare oncocytic variant of papillary thyroid gland carcinoma characterized by the presence of brisk lymphoplasmacytic infiltrate in the papillary stalks.
A group of malignant gliomas that includes anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma.
A rare yolk sac tumor that arises from the vulva.
An intraepithelial lesion of the vulvar squamous epithelium commonly associated with HPV infection. It includes low and high grade squamous intraepithelial lesions. Low grade squamous intraepithelial lesion is considered a non-neoplastic lesion. High grade squamous intraepithelial lesion is neoplastic.
A neuroendocrine carcinoma that arises from the vulva. It is characterized by the presence of malignant small cells with neuroendocrine differentiation. Most small cell neuroendocrine carcinomas of the vulva are Merkel cell carcinomas.
A benign glandular neoplasm that arises from the vulva. It presents as a mass or cystic lesion in or adjacent to the interlabial sulcus. It is characterized by the presence of complex branching papillae with fibrovascular stalks, lined by uniform columnar epithelial secretory cells and myoepithelial cells.
A neuroendocrine carcinoma that arises from the vulva. This category includes small cell and large cell neuroendocrine carcinoma. Most small cell neuroendocrine carcinomas of the vulva are Merkel cell carcinomas.
A Merkel cell carcinoma that arises from the vulva. It usually presents as a cutaneous nodular lesion. Most small cell neuroendocrine carcinomas of the vulva are Merkel cell carcinomas.
A benign, atypical, or dysplastic melanocytic nevus that arises from the vulva.
An uncommon benign neoplasm of the vulva, composed of lobules of mature adipocytes.
A high grade neuroendocrine carcinoma that arises from the vulva. It is characterized by the presence of malignant large cells with neuroendocrine differentiation.
A keratoacanthoma that arises from the vulva. It grows rapidly and may regress spontaneously. In some cases it is associated with prior trauma. Many cases diagnosed as keratoacanthomas show some degree of atypia and metastases have been reported. In such cases, the neoplasm is referred as squamous cell carcinoma, keratoacanthoma type.
A rare germ cell tumor that arises from the vulva.
A lipoma of the vulva with a predominant fibrous component.
A benign epithelial-stromal neoplasm that arises from the vulva and resembles the breast fibroadenoma.
A rare adenocarcinoma of intestinal type that arises from the vulva. The morphological features are those of a mucinous adenocarcinoma.
A rare adenocarcinoma arising from vulvar skin sweat glands.
A primary invasive malignant epithelial neoplasm of the vulva showing morphological features of recognized breast adenocarcinomas. (WHO, 2014)
The volume of blood remaining in a receptacle chamber at end ventricular systole.
The volume of blood remaining in a receptacle chamber at end ventricular diastole.
A response indicating that an individual is or was very tired.
A response indicating that an individual is or was very short of breath.
A score of 4 on the Combs Prognostic Index scale.
A response indicating that an individual is or was very energetic.
A response indicating a usual walking pace that is very brisk or striding, 4 mph or faster.
The indirect transmission of an infectious agent to a host via another living organism, either through purely mechanical means (e.g., insect bite) or by that organism supporting the growth or changes in the agent that make it infectious to the host.
A rare benign lesion that arises from the vagina. It is characterized by the presence of squamous epithelial and tubular structures in a fibrovascular stroma.
Vaginal metaplasia in which the vaginal surface squamous epithelium resembles benign transitional urothelium.
A rare benign cystic teratoma that arises from the vagina. It presents with a slow growing cyst in the vaginal wall that contains sebaceous material and hair. The cyst is lined by squamous epithelium. Skin adnexal structures and sometimes smooth and skeletal muscle are present.
A malignant mesenchymal neoplasm with skeletal muscle differentiation arising from the vagina.
A rare squamous cell carcinoma that arises from the vagina resembling transitional cell carcinoma of the urinary tract.
A rare neuroendocrine carcinoma that arises from the vagina. This category includes small cell and large cell neuroendocrine carcinoma.
An uncommon, benign, well circumscribed mesenchymal neoplasm that grows beneath the vaginal epithelium. It is characterized by the presence of cells containing bland ovoid, spindle, or stellate-shaped nuclei in a collagenous stroma.
A rare, aggressive neuroendocrine carcinoma that arises from the vagina and is characterized by the presence of malignant cells with abundant cytoplasm, large nuclei, and prominent nucleoli.
A germ tumor that arises from the vagina.
A rare benign lesion characterized by the presence of endocervical-type glands in the vaginal wall.
A usually benign neoplasm that arises from the uterine corpus. It resembles ovarian sex cord tumors. It lacks a component of recognizable endometrial stroma and the JAZF1-SUZ12 fusion which is characteristic of the endometrial stromal neoplasms.
A rare malignant heterologous neoplasm with skeletal muscle differentiation arising from the uterine corpus. It usually manifests with vaginal bleeding. The prognosis is poor.
An epithelial neoplasm with neuroendocrine differentiation that arises from the uterine corpus. It includes carcinoid tumor, small cell carcinoma pulmonary type, and large cell neuroendocrine carcinoma.
A variant of leiomyoma arising from the uterine corpus. It is characterized by conspicuous zonal edema. Hyalinization may also be present.
A benign or malignant germ cell tumor that arises from the uterine corpus. Representative examples include teratoma and yolk sac tumor.
A category of benign or malignant mesenchymal neoplasms that arises from the uterine corpus. This category includes the endometrial stromal nodule which is benign and non-invasive, the endometrial stromal sarcoma, and the undifferentiated uterine sarcoma. The endometrial stromal sarcoma is an invasive malignant neoplasm, further subdivided into low grade and high grade endometrial stromal sarcoma. Undifferentiated uterine sarcoma was previously also known as high grade endometrial stromal sarcoma. In 2014, high grade endometrial stromal sarcoma was reclassified and is currently considered a distinct and rare neoplasm. It appears to have a prognosis that falls between low grade endometrial stromal sarcoma and undifferentiated sarcoma.
A very rare and well differentiated neuroendocrine tumor that arises from the uterine corpus.
A response indicating that an individual used a telephone help line or quit line to quit smoking cigarettes.
A response indicating that an individual used the support of friends and family to quit smoking cigarettes.
A response indicating that an individual used a quit tobacco clinic, class, or support group to quit smoking cigarettes.
A response indicating that an individual used an internet or web-based program to quit smoking cigarettes.
A response indicating that an individual used books and/or pamphlets to quit smoking cigarettes.
An NIH upper GI score that has increased by 1 or more points, except 0 to 1.
An NIH upper GI score that has decreased by 1 or more points.
An NIH upper GI score of 0 after previous GvHD involvement.
A solid neoplasm that is not amenable to surgical resection.
A finding of unilateral bulging on pharyngeal contraction during swallowing.
A lesion that has overlapping histopathologic features that make its exact diagnosis and classification difficult.
A condition of decreased or absent presence of protein unc-13 homolog D. Deficiency of this protein is associated with familial hemophagocytic lymphohistiocytosis 3.
A response indicating that 2 to 3 hours were spent on an activity.
A response indicating that 2 to 5 hours were spent on an activity.
A response that indicates climbing two or less flights of stairs daily.
A response indicating that 21 to 40 hours were spent on an activity.
A response indicating that 20 to 59 minutes were spent on an activity.
A rare, cytologically high grade carcinoma that arises from the renal parenchyma. It is characterized by the presence of prominently dilated cystic spaces in a bland, fibrotic stroma. The lining cells have large irregular nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Necrosis and mitotic figures are not present. It rarely metastasizes.
Replacement of the endocervical-type epithelium of the cervix by benign tubal or endometrioid epithelium.
Benign proliferation of the fallopian tube epithelium.
The width of the vena contracta of the tricuspid valve.
The area of the vena contracta of the tricuspid valve.
The measured area of the backflow of blood into the right atrium.
A quantitative measurement of the amount of retrograde blood flow across the orifice of the tricuspid valve expressed as a percentage of the anterograde flow.
A relative measurement (ratio or percentage) the tricuspid regurgitant jet area to the right atrial area.
An erosion through the tracheal wall into an artery.
A finding of trace residue within or on pharyngeal structures following swallowing.
A finding of trace residue lining oral structures after swallowing.
A finding of a trace column of contrast or air between tongue base and posterior pharyngeal wall during swallowing.
A finding of a trace column of contrast or air between soft palate and pharyngeal wall during swallowing.
A finding of timely and efficient chewing and mashing prior to swallowing.
A response that indicates climbing three to four flights of stairs daily.
A response indicating that something happens or happened on three or four days.
A human immunoglobulin G1 (IgG1) monoclonal antibody directed against the complement pathway protein C5, with complement pathway inhibitory activity and potential immunomodulating activity. Upon administration, tesidolumab targets and binds to C5, thereby preventing both C5 convertase-mediated cleavage of C5 and the formation of C5a and C5b. This inhibits C5-mediated signal transduction, the formation of the membrane attack complex (MAC) and the activation of the terminal complement pathway, and results in the prevention and/or inhibition of both complement-mediated inflammation and cell destruction. C5 plays a key role in the activation of the complement cascade.
A response that indicates climbing ten to 14 flights of stairs daily.
A condition of decreased or absent presence of telomerase reverse transcriptase. Deficiency of this protein is associated with autosomal dominant dyskeratosis congenital 2, autosomal recessive dyskeratosis congenita 4, telomere-related pulmonary fibrosis, and bone marrow failure 1.
A condition of decreased or absent presence of telomerase RNA component. Deficiency of telomerase RNA component is associated with autosomal dominant dyskeratosis congenita 1, telomere-related pulmonary fibrosis, and bone marrow failure 2.
The qualitative measurement of the severity of the systolic anterior motion of a cardiac cusp.
A subjective score of 9 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 8 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 7 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 6 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 5 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 4 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 2 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 1 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 10 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A subjective score of 0 on a scale that ranges from 0: Did Not Interfere to 10: Interfered Completely.
A sustained-release (SR) hydrogel polymer-based formulation containing the antineoplastic antibiotic mitomycin C (MMC), with potential antineoplastic activity. Upon local administration of the SR MMC hydrogel formulation to the upper urinary tract via a ureteral catheter, the gel solidifies and deposits MMC locally to prevent the excretion of this chemotherapeutic agent via urinary flow. In turn, MMC alkylates DNA, and produces interstrand DNA cross-links, thereby inhibiting DNA synthesis. Due to its reverse thermal-gelation properties, this gel is able to stay in a liquid state at cold temperatures and solidifies at body temperature. This allows for increased accumulation of MMC locally in the upper urinary tract which leads to increased efficacy compared to standard intravesical delivery of MMC for upper tract urothelial carcinoma (UTUC).
An Iranian traditional herbal medicine composed of powder derived from sumac and Bunium persicum (black cumin, black zira), with potential anti-emetic activity. Upon oral administration, sumac/black cumin powder may inhibit chemotherapy-induced nausea and vomiting (CINV). The powder may also have some anti-oxidant activities.
A pathologic process that affects the loose connective tissue beneath the mucosa.
A response indicating that an individual is still doing an activity.
A response indicating that an individual stayed off cigarettes less than one day since their diagnosis.
A response indicating that an individual stayed off cigarettes the entire time since their diagnosis.
A response indicating that an individual is or was somewhat tired.
A response indicating that an individual is or has been somewhat dissatisfied or unhappy.
A response indicating that an individual has or had some energy.
A response indicating that an individual smoked at least one puff of a cigarette today.
A response indicating that an individual smoked a cigarette some days.
A response indicating that an individual smoked a cigarette every day.
A finding of slowed tongue motion during swallowing.
A finding of slow prolonged chewing or mashing with complete re-collection prior to swallowing.
An NIH skin score that has decreased by 1 or more points.
An NIH skin score of 0 after previous GvHD involvement.
A response indicating that 61 to 90 hours were spent on an activity.
A response indicating that 6 to 10 hours were spent on an activity.
A condition affecting gonadal and/or internal and/or external reproductive/genital development in which there is an atypical number of sex chromosomes (i.e. fewer or greater than the typical 2 X chromosomes or 1 X and 1 Y chromosome).
A subjective score of 9 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 8 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 7 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 6 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 5 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 4 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 3 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 2 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 10 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A subjective score of 0 on a severity scale that ranges from 0: Not at all severe to 10: most severe.
A rare non-invasive tumor that arises from the broad ligament. It is characterized by the presence of serous epithelial cell proliferation and cytological atypia.
A condition of decreased or absent presence of syntaxin-binding protein 2. Deficiency of this protein is associated with familial hemophagocytic lymphohistiocytosis type 5.
A mutation in the STAT3 gene that results in an increase in cytokine-related function. STAT3 mutations of this type are associated with infantile-onset multisystem autoimmune disease.
A mutation in the STAT1 gene that results in an increase in cytokine-related functions associated with IFN-alpha/beta, IFN-gamma, IFN-delta, and IL-27. STAT1 mutations of this type are associated with autosomal dominant immunodeficiency 31C.
A variation in the amino acid sequence for the succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial protein.
A change in the amino acid sequence at position 544 of the the succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial protein where arginine has been replaced by tryptophan.
A nucleotide substitution at position 1660 of the coding sequence of the SDHA gene where cytosine has been mutated to thymine.
A change in the nucleotide sequence of the SDHA gene.
A topical cream formulation containing the phosphate salt form of ruxolitinib, a bioavailable Janus-associated kinase (JAK) inhibitor, with potential immunomodulating activity. Upon topical administration of the ruxolitinib phosphate cream, ruxolitinib specifically binds to and inhibits the protein tyrosine kinases JAK 1 and 2; this inhibits signal transduction pathways of various cytokines and reduces inflammation. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling pathways initiated by many cytokines and growth factors; JAK kinases are upregulated in various inflammatory and autoimmune diseases, including alopecia areata.
A finding of residue on valleculae following swallowing.
A finding of residue on pyriform sinuses following swallowing.
A finding of oral residue remaining on lateral sulci after an individual swallows.
A finding of oral residue remaining on floor of mouth after an individual swallows.
A finding of residue on aryepiglottic folds following swallowing.
A finding of residue collection on oral structures after swallowing.
A finding of repetitive or disorganized tongue motion during swallowing.
Acute lymphoblastic leukemia that occurs in adulthood and does not respond to treatment.
A malignant solid neoplasm that has recurred after a period of remission.
The reemergence of non-squamous non-small cell lung carcinoma after a period of remission.
The reemergence of glioblastoma after a period of remission.
The reemergence of a gastrointestinal stromal tumor after a period of remission.
A qualitative assessment of the status of a biological specimen with regards to a cellular receptor.
A cytogenetic abnormality that refers to any translocation involving the RET gene.
A response indicating that an individual is or was quite a bit of tired.
A response indicating that an individual has or had quite a bit of energy.
A response indicating that an individual is or was quite a bit short of breath.
A subjective rating score of 9 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A subjective rating score of 8 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A subjective rating score of 7 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A subjective rating score of 6 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A subjective rating score of 5 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A subjective rating score of 4 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A subjective rating score of 2 on a linear analogue scale with anchor point descriptions of 0:As bad as it can be and 10: As good as it can be.
A subjective rating score of 1 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A subjective rating score of 10 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
A subjective rating score of 0 on a linear analogue scale with anchor point descriptions of 0: As bad as it can be and 10: As good as it can be.
The measured width of the backflow of blood into the right ventricular outflow tract.
A relative measurement (ratio or percentage) of the pulmonic regurgitant jet width to the right ventricular outflow tract diameter.
The determination of whether blood flow in the pulmonary veins is greater during ventricular systole or diastole.
The width of the vena contracta of the pulmonic valve.
The area of the vena contracta of the pulmonic valve.
A morphologic finding indicating the presence of an exuberant proliferation of fibroblasts and myofibroblasts in the stroma of a tumor sample.
A serous adenocarcinoma that arises from the lining of the peritoneum. It is characterized by low grade histopathologic features.
A serous adenocarcinoma that arises from the lining of the peritoneum. It is characterized by high grade histopathologic features.
Supranormal glucocorticoid concentrations resulting from a condition originating within the adrenal gland.
An abscess that develops in the tissues within the prevertebral fascia.
There is evidence of disease without evidence of unequivocal progression.
A rare, benign, non-neoplastic reactive lesion that develops in the vagina at the site of a prior operative procedure. It is composed of spindle cells, small blood vessels, and chronic inflammation.
A rare, benign, non-neoplastic reactive lesion that develops in the cervix at the site of a prior operative procedure. It is composed of spindle cells, small blood vessels, and chronic inflammation.
A finding of posterior escape of less than half of bolus during swallowing.
A finding of posterior escape of greater than half of bolus during swallowing.
A score of 3 on the Combs Prognostic Index scale.
A numerical chromosomal abnormality characterized by the presence of more than two copies of chromosome 7 in a cell.
A photosensitizer composed of the sodium salt form of chlorin e6 and its derivatives complexed with a low-molecular weight polyvinylpyrrolidone (PVP) polymer component, with diagnostic and antineoplastic activities upon photodynamic therapy (PDT). Upon intravenous administration, the photosensitizer phytochlorin-PVP sodium complex preferentially accumulates in hyperproliferative tissues, such as tumors. Local application of light with a certain wavelength to the tumor site results in the absorption of light by this agent leading to its photoactivation. This results in a photodynamic reaction between phytochlorin and oxygen, which causes the production of reactive oxygen species (ROS), including singlet oxygen molecules, the superoxide ion, and other cytotoxic free radicals. The formation of ROS induces free radical-mediated oxidative DNA damage followed by apoptosis of tumor cells. Chlorin e6-PVP is able to penetrate deeply into tissues and is therefore able to treat hard-to-reach tumors.
A finding of a pharyngeal stripping wave present but diminished.
A finding of a pharyngeal stripping wave present and complete.
An assessment of an individual's pharyngeal impairment during swallowing.
A rare, usually benign fibroblastic neoplasm that arises from the peritoneum. It is characterized by the presence of prominent hemangiopericytoma-like vessels.
A desmoplastic small round cell tumor that occurs in the abdominal and/or pelvic peritoneum.
A very rare peripheral T-cell lymphoma with pathologic and clinical features posing difficulty in its exact diagnosis and classification.
A condition of decreased or absent presence of perforin. Deficiency of this protein is associated with T-cell lymphoblastic lymphoma, aplastic anemia, hemophagocytic lymphohistiocytosis familial type 2, autoimmune lymphoproliferative syndrome and other lymphoproliferative disorders, including various forms of lymphoma.
Fibromatosis that occurs in the pelvis. It affects almost always females. It is characterized by the presence of elongated spindle-shaped fibroblasts, collagenous stroma formation, and an infiltrative growth pattern. It recurs if incompletely resected but lacks metastatic potential.
An analogue of pegfilgrastim, a recombinant, pegylated form of endogenous human granulocyte colony-stimulating factor (G-CSF), with hematopoietic activity. Similar to endogenous G-CSF, this agent binds to and activates specific cell surface receptors, and stimulates neutrophil progenitor proliferation, differentiation and selected neutrophil functions. Pegteograstim may prevent and shorten the duration of chemotherapy-induced neutropenia (CIN). Pegylation of teograstim increases the half-life of this agent.
The maximum rate of blood flow across a cardiac valve during early diastole (passive ventricular filling).
The measurement of the maximum rate of blood flow across an area or tissue.
The maximum rate of blood flow across a cardiac valve during late diastole (active ventricular filling).
A finding of minimal superior movement of thyroid cartilage with minimal approximation of arytenoids to epiglottic petiole during swallowing.
A finding of partial superior movement of thyroid cartilage/partial approximation of arytenoids to epiglottic petiole during swallowing.
A finding of partial inversion of epiglottis during swallowing.
A finding of partial distension or partial duration of pharyngoesophageal segment opening during swallowing; partial obstruction of flow.
A finding of partial anterior movement of hyoid during swallowing.
A combination of betel leaf, areca nut, and tobacco. It is chewed for its stimulant and psychoactive effects.
A change in the nucleotide sequence of the PRSS2 gene.
A change in the nucleotide sequence of the PRSS1 gene.
A condition of decreased or absent presence or activity of phosphoglucomutase 3. Deficiency of this protein is associated with immunodeficiency 23.
A variation in the amino acid sequence of the platelet-derived growth factor receptor beta protein.
A change in the nucleotide sequence of the PDGRFB gene.
Difference of sex development characterized by the presence of ovarian and testicular tissue in the same individual. The clinical manifestations of the condition, which can be associated with 46,XX, 46,XY or 46,XX/46,XY mosaic karyotype, are variable.
A response indicating that over 90 hours were spent on an activity.
A non-metastasizing cystic mixed epithelial neoplasm that arises from the ovary. It is characterized by the presence of more than one epithelial cell type, most often serous and endocervical-type mucinous.
A non-metastasizing mixed epithelial neoplasm that arises from the ovary. It is characterized by the presence of more than one epithelial cell type, most often serous and endocervical-type mucinous and prominent fibrous stroma..
A retiform Sertoli-Leydig cell tumor that arises from the ovary. It is characterized by the presence of an epithelial and/or mesenchymal heterologous component.
A rare usually bilateral luteinized thecoma that arises from the ovary and is associated with sclerosing peritonitis. It occurs mostly in premenopausal women. The ovarian tumor is benign but patients may develop intestinal obstruction due to the sclerosing peritonitis.
A category of rare neoplasms that arise from the ovary. It includes low grade endometrioid stromal sarcoma and undifferentiated sarcoma.
A rare benign mesothelial tumor that arises from the ovary. It is characterized by the presence of gland-like structures.
A high-grade carcinoma that arises from the oropharynx. It is characterized by the presence of malignant cells which bear minimal resemblance to the cells from which they arose.
A high-grade variant of squamous cell carcinoma that arises from the oropharynx. It is characterized by the presence of small malignant cells with hyperchromatic nuclei and scant amount of cytoplasm forming lobules with peripheral palisading.
An observation of oral residue remaining after an individual swallows.
A response indicating that 1 to 1 1/2 hours were spent on an activity.
A response indicating that 1 to 4 minutes were spent on an activity.
A response indicating that one hour (60 minutes) was spent on an activity.
An oligodendroglioma carrying IDH gene family mutation and combined whole-arm losses of 1p and 19q (1p/19q codeletion).
A response indicating that an individual is or was not at all tired.
A response indicating that an individual is or was not at all short of breath.
A response indicating a usual walking pace that is normal or average, 2-2.9 mph.
A nonencapsulated variant of papillary carcinoma of the thyroid gland characterized by the predominance of follicular structures. The malignant follicular cells display the nuclear features that characterize the papillary adenocarcinomas of the thyroid gland.
Failure to thrive caused by inadequate intake due to environmental influences, stimulus deprivation- poverty, feeding techniques, or psychological reason, and without any apparent growth-inhibiting organic disorder.
A rare morphologic variant of papillary thyroid gland carcinoma characterized by the presence of prominent stromal reaction.
Nodular proliferation of normal Bartholin gland tissue and ducts.
A finding of no visible posterior motion of tongue base during swallowing.
A finding of no visible initiation of pharyngeal swallow at any location.
A finding of no superior movement of thyroid cartilage during swallowing.
A finding of no labial escape during swallowing.
A finding of no inversion of epiglottis during swallowing.
A response indicating that an individual has or had no energy at all.
A finding of no distension of pharyngoesophageal segment opening during swallowing with total obstruction of flow.
A finding of no contrast between tongue base and posterior pharyngeal wall during swallowing.
A finding of no bolus between soft palate/pharyngeal wall during swallowing.
A finding of no anterior movement of hyoid during swallowing.
A response indicating that an individual never smoked cigarettes regularly.
A response indicating that an individual is never did an activity.
Nephrotic syndrome in which there is a relapse occuring less than twice in the first six months, or less than four times in a year.
A localized pathological or traumatic structural change due to insertion and/or withdrawal of a needle.
A response indicating that something happens or happened nearly every day for two weeks.
A finding of a narrow column of contrast or air between tongue base and posterior pharyngeal wall during swallowing.
A peptide-based cancer vaccine comprised of synthetic peptides derived from the cancer-testis antigen NY-ESO-1, preferentially expressed antigen in melanoma (PRAME), human melanoma antigen A3 (MAGE-A3) and the human Wilms tumor protein-1 (WT-1), with potential immunostimulating and antineoplastic activities. Upon administration, NY-ESO-1/PRAME/MAGE-A3/WT-1 peptide vaccine may stimulate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing NY-ESO-1, PRAME, MAGE-A3 and WT-1, resulting in tumor cell lysis. The NY-ESO-1, PRAME, MAGE-A3 and WT-1 peptides, tumor-associated antigens (TAAs) overexpressed in a variety of cancer cell types, play a key role in tumor cell proliferation.
A combination preparation composed of a protein derived from the human tumor-associated antigen (TAA) cancer-testis antigen 1 (NY-ESO-1) and a microparticle combining two immune-modifying components derived from the bacterium Propionibacterium acnes, a bacterial cell wall component that is rich in muramyl dipeptide (MDP) and bacteria-derived single-stranded DNA fragments, with potential immunomodulating, immunoadjuvant and antineoplastic activities. Upon administration of NY-ESO-1 protein/microparticle MDP/bacterial DNA-containing MIS416 vaccine, MIS416 localizes in and is taken up mainly by the liver, thereby forming a liver depot. MIS416 is then taken up by immune cells, such as monocytes and dendritic cells (DCs), where MDP and the bacterial DNA target and bind to the cytosolic innate pattern recognition receptors (PRRs) nucleotide-binding oligomerization domain-containing protein 2 (NOD2), and toll-like receptor 9 (TLR9), respectively. The simultaneous binding and activation of both NOD2 and TLR9, leads to activation of both NOD2 and TLR9 signaling pathways. This stimulates the innate immune system, induces secretion of cytokines, particularly interferon (IFN), and modulates the activation of various immune cells. In the presence of the NY-ESO-1 peptide, MIS416 enhances the cytotoxic T-lymphocyte (CTL)-mediated immune response against NY-ESO-1, resulting in an increased anti-tumor immune response. NY-ESO-1 is expressed in normal testes and on the surfaces of various tumor cells, and plays a key role in tumor cell proliferation and survival.
A very rare NK-cell lymphoma with pathologic and clinical features posing difficulty in its exact diagnosis and classification.
A subtype of adrenal hyperplasia, based on histopathologic features, in which there are multiple nodules.
An NIH modified Oral Mucosa Rating Scale (OMRS) score that has increased by 2 or more points.
An NIH modified Oral Mucosa Rating Scale (OMRS) score that has decreased by 2 or more points.
An NIH modified Oral Mucosa Rating Scale (OMRS) score of 0 following previous GvHD involvement.
A non-seminomatous germ cell tumor arising from the testis of a mouse, characterized by the presence of various tissues corresponding to the different germinal layers (endoderm, mesoderm, and ectoderm).
An indication that something happens or happened most or almost most of the time.
An indication that something happens or happened moderately or much of the time.
A response indicating that an individual is or was moderately tired.
A response indicating that an individual is or was moderately energetic.
A score of 2 on the Combs Prognostic Index scale.
Failure to thrive due to both organic and non-organic causes.
The width of the vena contracta of the mitral valve.
The measured area of the backflow of blood into the left atrium.
A relative measurement (ratio or percentage) of the mitral regurgitant jet area to left atrial area.
The ratio of the peak early diastolic transmitral velocity to the peak mitral annular motion velocity.
The ratio of the rate of blood flow during early diastole to the rate of blood flow during late diastole.
An immunoconjugate consisting of the humanized monoclonal antibody M9346A against folate receptor 1 (FOLR1) conjugated, via the disulfide-containing cleavable linker sulfo-SPDB, to the cytotoxic maytansinoid DM4, with potential antineoplastic activity. The anti-FOLR1 monoclonal antibody moiety of mirvetuximab soravtansine targets and binds to the cell surface antigen FOLR1. After antibody-antigen interaction and internalization, the immunoconjugate releases DM4, which binds to tubulin and disrupts microtubule assembly/disassembly dynamics, thereby inhibiting cell division and cell growth of FOLR1-expressing tumor cells. FOLR1, a member of the folate receptor family is overexpressed on a variety of epithelial-derived cancer cells. The sulfo-SPDB linker prevents cleavage in the bloodstream and may improve this agent's efficacy in multidrug resistant tumor cells.
The cross sectional diameter a cardiovascular structure measured in the minor axis at end ventricular systole.
The cross sectional diameter a cardiovascular structure measured in the minor axis at end ventricular diastole.
A finding of minimal to no tongue motion during swallowing.
A finding of minimal to no pharyngeal clearance following swallowing.
A finding of minimal to no esophageal clearance.
A finding of minimal to no clearance of bolus after swallowing.
A finding of minimal distension or minimal duration of pharyngoesophageal segment opening during swallowing; marked obstruction of flow.
A finding of minimal chewing or mashing with majority of bolus unchewed prior to swallowing.
An aggressive variant of lung adenocarcinoma that exhibits a micropapillary architectural pattern. The prognosis is usually poor.
An extended-release (ER) tablet composed of the hydrochloride salt form of the biguanide metformin and the hydrochloride salt form of the thiazolidinedione pioglitazone, with antihyperglycemic activity. Upon oral administration and although the exact mechanism of action has yet to be fully elucidated, metformin inhibits complex I (NADPH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain and increases the cellular AMP to ATP ratio leading to activation of AMP-activated protein kinase (AMPK). This modulates AMPK-mediated transcription of target genes, which prevents hepatic gluconeogenesis, decreases intestinal absorption of glucose, enhances insulin sensitivity and fatty acid oxidation, and increases glucose uptake and utilization in target tissues. Pioglitazone binds to and activates the transcription factor peroxisome proliferator-activated receptor gamma (PPAR-gamma), thereby increasing the transcription of insulin-responsive genes. This enhances insulin sensitivity of insulin-dependent tissues, decreases insulin resistance, enhances peripheral glucose utilization, and decreases hepatic glucose output. Altogether, this lowers blood glucose levels.
An urothelial carcinoma which has spread from the original site of growth to another anatomic site.
A non-squamous non-small cell carcinoma that arises from the lung and has metastasized to another anatomic site.
A carcinoma that arises from the head and neck and has spread from the original site of growth to another anatomic site.
Membranous nephropathy due to another medical condition.
A microscopic finding indicating the presence of mammary gland type morphological features in a tumor sample.
A low or high grade malignant phyllodes tumor arising from specialized anogenital glands.
A malignant neoplasm with perivascular epithelioid cell differentiation arising from the uterine corpus. The neoplasm is usually a large size, and charcaterized by the presence of marked nuclear atypia, pleomorphism, increased mitotic activity, necrosis, and infiltrative margins. The most common metastatic sites are lungs, lymph nodes, and bone. Patients present with a pelvic mass or abnormal bleeding.
A rare malignant mesenchymal neoplasm that arises from the cervix.
A finding of the majority of contrast within or on pharyngeal structures following swallowing.
A finding of the majority of bolus remaining after swallowing.
A major congenital anomaly is a structural or functional defect with the following three characteristics: 1) Of prenatal origin; 2) Present at the time of live birth or fetal demise, or in utero; 3) Affecting (or has the propensity to affect) the health, survival, or physical or cognitive functioning of the individual.
The cross sectional diameter of a cardiovascular structure measured along the major axis at end ventricular systole.
The cross sectional diameter of a cardiovascular structure measured along the major axis at end ventricular diastole.
A variation in the amino acid sequence of the myeloid differentiation primary response protein MyD88.
A change in the amino acid residue at position 265 in the myeloid differentiation primary response protein MyD88 where leucine has been replaced by proline.
A change in the nucleotide sequence of the MYD88 gene.
A nucleotide substitution at position 1544 of the coding sequence of the MPL gene where guanine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 1543 and 1545 of the coding sequence of the MPL gene has changed from thymine-guanine-guanine to adenine-adenine-adenine.
A complex substitution where the nucleotide sequence at positions 1543 and 1544 of the coding sequence of the MPL gene has changed from thymine-guanine to adenine-adenine.
A change in the nucleotide sequence of the MPL gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 14 of the MET gene located in the vicinity of 7q31.
Either an increase by 10% predicted absolute value of %FEV1 or an NIH lung symptom score that has decreased by 1 or more points.
Either normal %FEV1, alkaline phosphatase, and total bilirubin after previous elevation of 1 or more or an NIH lung symptom score of 0 following GvHD involvement.
An NIH lower GI score that has increased by 1 or more points, except 0 to 1.
An NIH lower GI score that has decreased by 1 or more points.
An NIH lower GI score of 0 after previous GvHD involvement.
A slow-growing serous adenocarcinoma that arises from the fallopian tube. It is characterized by the presence of low grade cytologic features and infrequent mitotic figures.
A slow-growing serous adenocarcinoma that arises from the broad ligament. It is characterized by the presence of low grade cytologic features and infrequent mitotic figures.
Lobular proliferations of benign-appearing small to moderate sized endocervical glands in the inner half of the cervical stroma. The glands are lined by columnar epithelial cells which contain pyloric gland-type mucin. There is minimal atypia and mitotic figures are rare. Some cases have been associated with adenocarcinoma in situ/high grade cervical glandular intraepithelial neoplasia and gastric-type adenocarcinomas.
An increase by two times the upper limit of normal for ALT, alkaline phosphatase, and total bilirubin.
Normal ALT, alkaline phosphatase, and total bilirubin after previous elevation of 1 or more following GvHD involvement.
The integral of all of the flow velocities within the left ventricular outflow tract during ventricular systole.
The measurement of the maximum rate of blood flow measured in the left ventricular outflow tract during systole.
Prosthetic valve endocarditis that occurs several months to years following valve replacement.
The assessment of the largest cross-sectional thickness of a tissue.
The largest cross sectional diameter measured at end ventricular diastole.
A combination of tobacco and slaked lime paste with or without areca nut. It is placed between the cheek and gum and is a mild stimulant.
A variation in the amino acid sequence for the mast/stem cell growth factor receptor Kit protein.
A change in the amino acid residue at position 816 in the mast/stem cell growth factor receptor Kit protein where asparagine has been replaced by valine.
A nucleotide substitution at position 2447 of the coding sequence of the KIT gene where adenine has been mutated to thymine.
A molecular genetic abnormality indicating the presence of a mutation in exon 8 of the KIT gene located within 4q11-q12.
A NIH joint and fascia score that has increased by 1 or more points or a decrease in P-ROM score by 1 point for any site.
A NIH Joint and Fascia score that has decreased by 1 or more points or an increase in P-ROM score by 1 point for any site.
Both an NIH joint and fascia score of 0 and a P-ROM score of 25 after previous GvHD involvement by at least 1 measure.
A finding of interlabial escape during swallowing, but no progression to anterior lip.
An observation of an individual's initiation of pharyngeal swallow.
A finding of pharyngeal swallow initiated with bolus head in valleculae.
A finding of pharyngeal swallow initiated with bolus head in pyriforms.
A finding of pharyngeal swallow initiated with bolus head at posterior angle of ramus.
A finding of pharyngeal swallow initiated with bolus head at posterior laryngeal surface of epiglottis.
Hidradenitis that is caused by an infectious agent, usually a bacterium.
A T acute lymphoblastic leukemia that occurs in infancy.
An acute undifferentiated leukemia that occurs in infancy.
An acute biphenotypic leukemia that occurs in infancy.
The transmission of an infectious agent from a source to a host through an intermediary such as inanimate objects (vehicles) or living organisms (vectors).
A finding indicating an increase in the numbers of epithelial cells that have been transformed into mucus-secreting cells. This does not include the normal increase in mucification seen in the estrous cycle.
A finding of incomplete pharyngeal contraction during swallowing.
A finding of incomplete laryngeal vestibular closure; narrow column air/contrast in laryngeal vestibule.
An observation of an individual's tongue control during bolus hold.
An observation of an individual's tongue base retraction during swallowing.
An observation of an individual's soft palate elevation during swallowing.
An observation of an individual's pharyngoesophageal segment opening during swallowing.
An observation of an individual's pharyngeal stripping wave during swallowing.
An observation of an individual's pharyngeal contraction during swallowing.
An observation of an individual's laryngeal vestibular closing and height of swallowing.
An observation of an individual's esophageal clearance after swallowing in an upright position.
An observation of an individual's epiglottic movement during swallowing.
An observation of an individual's bolus transport and lingual motion during swallowing.
An observation of an individual's bolus preparation and/or mastication prior to swallowing.
An observation of an individual's anterior hyoid excursion during swallowing.
A condition of compromised immune function resulting from an uncharacterized defect.
Chronic degenerative changes in the kidney characterized by thickened and inflamed glomeruli and proteinurea, the cause of which is unknown.
Botulism that occurs following injection of botulinum toxin.
A condition of decreased or absent presence or activity of interferon gamma receptor 1. Deficiency of this protein is associated with immunodeficiency 27A and immunodeficiency 27B.
A change in the amino acid residue at position 132 in the isocitrate dehydrogenase [NADP] cytoplasmic protein where arginine has been replaced by histidine.
A complex substitution where the nucleotide sequence at positions 395 and 396 of the coding sequence of the IDH1 gene has changed from thymine-guanine to adenine-cytosine.
A nucleotide substitution at position 395 of the coding sequence of the IDH1 gene where guanine has been mutated to adenine.
A transient condition associated with urinary tract infections in infants presenting with hyponatremia and hyperkalemia, mimicking low concentrations of aldosterone.
An autosomal dominant condition presenting with hyponatremia and hyperkalemia, mimicking low concentrations of aldosterone, associated with loss-of-function mutation(s) in the NR3C2 gene, encoding the mineralocorticoid receptor.
A condition of decreased or absent presence or activity of V(D)J recombination-activating protein 1. Deficiency of this protein is associated with Omenn syndrome, severe combined immunodeficiency, b cell-negative, combined cellular and humoral immune defects with granulomas, and alpha/beta T-cell lymphopenia with gamma/delta T-cell expansion, severe cytomegalovirus infection, and autoimmunity.
A genetically heterogynous condition characterized by hyperkalemia, hyperchloremic acidosis, low or suppressed renin activity, and normal to high concentrations of aldosterone. Mutations in genes (for example WNK1 or WNK4), regulating Na-Cl cotransporters (NCC), Na-K-Cl cotransporters (NKCC2), or the renal outer medullary potassium (ROMK) channel have been identified as causative in this condition. The primary abnormality is thought to be a specific defect of the renal secretory mechanism for potassium, which limits the kaliuretic response to, but not the sodium and chloride reabsorptive effect of, mineralocorticoid.
The transmission of a disease from one individual to another.
A rapidly growing serous adenocarcinoma that arises from the fallopian tube. It is characterized by the presence of high grade cytologic features and frequent mitotic figures.
A rapidly growing serous adenocarcinoma that arises from the broad ligament. It is characterized by the presence of high grade cytologic features and frequent mitotic figures.
An infection that is caused by hepatitis C virus.
A response indicating that an individual has stopped doing an activity.
A response indicating that an individual has not smoked since they have been diagnosed with cancer.
A response indicating that an individual has not been treated for cancer.
A response indicating that an individual has not had surgery for cancer.
A response indicating that an individual has not completed treatment for cancer.
A response indicating that an individual has not been diagnosed with cancer.
A response indicating that an individual is or has been happy most of the time.
A peptide vaccine comprised of synthetic human leukocyte antigen (HLA)-A2-restricted peptides derived from the tumor-associated antigens (TAAs) interleukin-13 receptor alpha-2 (IL-13Ra2), the tyrosine kinase receptor Ephrin receptor A2 (EphA2), and the apoptosis inhibitor protein survivin, combined with the adjuvant tetanus toxoid (TT)-derived helper T-cell peptide, and emulsified in the immunoadjuvant Montanide ISA-51, with potential immunostimulating and antineoplastic activities. Specifically, this vaccine contains the epitopes: IL-13Ralpha2 345-353:1A9V, which is an engineered peptide based on amino acids 345-353 of IL-13Ra2 where the amino acids at the first and ninth positions of the peptide have been replaced with alanine and valine, respectively, EphA2 883-891, and survivin 96-104. Upon administration, the HLA-A2-restricted IL-13Ra2/EphA2/survivin/TT T-helper epitopes-Montanide 51 vaccine may stimulate a HLA-A2-restricted cytotoxic T-lymphocyte (CTL) response against tumor cells that overexpress IL-13Ra2, EphA2, or survivin, and results in tumor cell lysis. TT T-helper peptide binds to class II major histocompatibility molecules (MHC) molecules as a nonspecific vaccine helper epitope, resulting in long-term immunopotentiation by increasing the helper T-cell response. Montanide ISA-51, a stabilized water-in-oil emulsion adjuvant containing mineral oil with mannide monooleate added as a surfactant, non-specifically stimulates cell-mediated immune responses to antigens. IL-13Ra2, EphA2 and survivin, TAAs that are overexpressed in certain tumor cell types, play key roles in tumor cell proliferation. HLA-A2 presents antigenic peptides to CD8+ T-cells; epitope design restricted to epitopes that bind most efficiently to HLA-A2 may improve peptide immunogenicity.
A variation in the amino acid sequence for the histone h3 protein.
A molecular abnormality indicating the presence of histone H3 K27M mutation.
The histopathological evaluation of staining in tissue based on the H Score scoring system (McCarty KS Jr, Miller LS, Cox EB, et al. Estrogen receptor analyses: correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985;109(8):716-721).
A combination of crushed areca nut, tobacco, catechu, paraffin wax, slaked lime, and sweet or savory flavorings. It is placed between the cheek and gum and is a mild stimulant.
A pituitary gland adenoma composed of acidophilic cells that produce both growth hormone and prolactin. It is characterized by the detection of growth hormone and prolactin within the same acidophilic cell, or an admixture of acidophilic and chromophobic cells that produce growth hormone and prolactin respectively.
A score of 1 on the Combs Prognostic Index scale.
A clinician overall severity score that has increased by 2 or more points on a 0-10 scale.
A clinician overall severity score that has decreased by 2 or more points on a 0-10 scale.
A clinician overall severity score 0 following GvHD response.
A glioblastoma characterized by the presence of well-demarcated nodules which contain primitive cells exhibiting neuronal differentiation.
A poorly differentiated squamous cell carcinoma that arises from the gingiva. It is characterized by the presence of malignant pleomorphic spindle cells.
Gemistocytic astrocytoma carrying IDH mutations.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the gastroesophageal junction. According to the size of the malignant cells, the prominence of the nucleoli, and the amount of cytoplasm, it is classified either as small or large cell neuroendocrine carcinoma.
An aggressive, high-grade and poorly differentiated carcinoma with neuroendocrine differentiation that arises from the gastroesophageal junction. It is characterized by the presence of malignant large cells.
A response indicating that an individual is or was full of energy.
A response indicating that 41 to 60 hours were spent on an activity.
An orally available inhibitor of poly (ADP-ribose) polymerase (PARP) types 1 and 2, with potential antineoplastic activity. Upon oral administration, fluzoparib inhibits PARP 1 and 2 activity, which inhibits PARP-mediated repair of damaged DNA via the base excision repair (BER) pathway, enhances the accumulation of DNA strand breaks, promotes genomic instability, and leads to an induction of apoptosis. The PARP family of proteins catalyze post-translational ADP-ribosylation of nuclear proteins, which then transduce signals to recruit other proteins to repair damaged DNA. PARP inhibition may enhance the cytotoxicity of DNA-damaging agents and may reverse tumor cell chemoresistance and radioresistance.
A response indicating that something happens or happened between five and seven days.
A response indicating that 5 to 19 minutes were spent on an activity.
A response that indicates climbing five to nine flights of stairs daily.
A response that indicates climbing 15 or more flights of stairs daily.
Metaplastic mucinous changes in the fallopian tube epithelium. It may be seen in association with gynecological, appendiceal, or colonic mucinous tumors, or chronic inflammation.
An exceedingly rare lymphoma that arises from the fallopian tube.
A variation in the amino acid sequence for the receptor-type tyrosine-protein kinase FLT3 protein.
A change in the amino acid residue at position 835 in the receptor-type tyrosine-protein kinase FLT3 protein where asparagine has been replaced by another amino acid.
A change in the nucleotide sequence of the FLT3 gene.
Ovarian cancer with hepatic and/or splenic parenchymal metastasis, metastasis to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity). (FIGO, 2014)
Ovarian cancer with pleural effusion with positive cytology. (FIGO, 2014)
Ovarian cancer with microscopic, extrapelvic (above the brim) peritoneal involvement +/- positive retroperitoneal lymph nodes. (FIGO, 2014)
Ovarian cancer with positive retroperitoneal lymph nodes only. Metastasis greater than 10 mm. (FIGO, 2014)
Ovarian cancer with positive retroperitoneal lymph nodes only. Metastasis equal or less than 10 mm. (FIGO, 2014)
Ovarian cancer with positive retroperitoneal lymph nodes only. (FIGO, 2014)
Stage IC ovarian cancer with malignant cells in the ascites or peritoneal washings. (FIGO, 2014)
Stage IC ovarian cancer with capsule rupture before surgery or tumor on ovarian surface. (FIGO, 2014)
Stage IC ovarian cancer with surgical spill. (FIGO, 2014)
A change in the amino acid residue at position 373 in the fibroblast growth factor receptor 3 protein where tyrosine has been replaced by cysteine.
A change in the amino acid residue at position 371 in the fibroblast growth factor receptor 3 protein where serine has been replaced by cysteine.
A change in the amino acid residue at position 249 in the fibroblast growth factor receptor 3 protein where serine has been replaced by cysteine.
A change in the amino acid residue at position 284 in the fibroblast growth factor receptor 3 protein where arginine has been replaced by cysteine.
A change in the amino acid residue at position 380 in the fibroblast growth factor receptor 3 protein where glycine has been replaced by arginine.
A change in the amino acid residue at position 370 in the fibroblast growth factor receptor 3 protein where glycine has been replaced by cysteine.
A nucleotide substitution at position 746 of the coding sequence of the FGFR3 gene where cytosine has been mutated to guanine.
A nucleotide substitution at position 742 of the coding sequence of the FGFR3 gene where cytosine has been mutated to thymine.
A nucleotide substitution at position 1138 of the coding sequence of the FGFR3 gene where guanine has been mutated to adenine.
A nucleotide substitution at position 1118 of the coding sequence of the FGFR3 gene where adenine has been mutated to guanine.
A nucleotide substitution at position 1111 of the coding sequence of the FGFR3 gene where adenine has been mutated to thymine.
A nucleotide substitution at position 1108 of the coding sequence of the FGFR3 gene where guanine has been mutated to thymine.
A change in the nucleotide sequence of the F2 gene.
An NIH eye score that has increased by 1 or more points, except 0 to 1.
An NIH eye score that has decreased by 1 or more points.
An NIH eye score of 0 after previous GvHD involvement.
A response indicating that an individual is or was extremely tired.
A response indicating that an individual is or was extremely short of breath.
A malignant neoplasm arising from foci of atypical fibroblast-like cells in the interstitium of the outer stripe of the outer medulla of the kidney. (INHAND)
A malignant neoplasm arising from neuroendocrine cells with evidence of invasion.
A benign neoplasm arising from neuroendocrine cells.
A benign neoplasm composed of Sertoli cells arranged in tubules intermixed with pleomorphic Leydig cells.
A benign neoplasm arising from pluripotent mesodermal cells of the Mullerian ducts. (INHAND)
A benign epithelial neoplasm arising from the endometrium.
A score of 0 on the Combs Prognostic Index scale.
A non-adhesive, non-absorbable, permanent liquid embolic agent comprised of ethylene vinyl alcohol (EVOH) copolymer dissolved in dimethyl sulfoxide (DMSO), and of micronized tantalum powder that can be used to occlude blood vessels. Upon administration of the EVOH-based embolic agent, contact with fluids, such as blood, induces the solidification of EVOH into a sponge-like material. This causes occlusion of blood vessels and prevents blood flow to the treated area.
An NIH esophagus score that has increased by 1 or more points, except 0 to 1.
An NIH esophagus score that has decreased by 1 or more points.
An NIH esophagus score of 0 after previous GvHD involvement.
A finding of esophageal retention with retrograde flow through the pharyngoesophageal segment.
A finding of esophageal retention with retrograde flow below the pharyngoesophageal segment.
A finding of esophageal retention following swallowing.
An assessment of an individual's esophageal impairment during swallowing.
A finding of escape to nostril with or without emission during swallowing.
A finding of escape to nasopharynx during swallowing.
A finding of escape to nasal cavity during swallowing.
A finding of escape to lateral buccal cavity/floor of mouth during swallowing.
A finding of escape progressing to mid-chin during swallowing.
A finding of escape from interlabial space or lateral juncture during swallowing, but no extension.
A finding of escape beyond mid-chin during swallowing.
An IDH-wildtype glioblastoma characterized by the presence of large epithelioid cells with abundant eosinophilic cytoplasm, vesicular chromatin, and prominent nucleoli.
An ependymoma characterized by gene fusions involving RELA, a transcription factor involved in NK-kB pathway activity. It accounts for the majority of supratentorial ependymomas in children. It has an unfavorable outcome when compared to other ependymoma subtypes.
A preparation of autologous T-lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the antigen epithelial cell adhesion molecule (EpCAM), with potential immunostimulating and antineoplastic activities. Upon administration, the EpCAM-specific CAR-expressing autologous T-lymphocytes specifically recognize and bind to EpCAM-expressing tumor cells, resulting in tumor cell lysis. EpCAM, a cell surface protein, is expressed by a variety of tumor cells.
A category of rare neoplasms that arise from the vagina. It includes low grade endometrioid stromal sarcoma and undifferentiated sarcoma.
A category of rare neoplasms that arise from the cervix. It includes low grade endometrioid stromal sarcoma and undifferentiated endocervical sarcoma.
Dense diffuse and superficial infiltration of the endometrium by lymphoid cells. It is typically seen in association with chronic endometritis.
A high grade neuroendocrine neoplasm that arises from the endometrium. It is composed of large polygonal cells arranged in well-demarcated nests, trabeculae or cords with peripheral palisading.
A carcinoma that arises from the endometrium and is characterized by the presence of an undifferentiated carcinomatous component and a second component of either FIGO grade 1 or 2 endometrioid carcinoma.
An infection caused by an infectious agent that is present on or in the host prior to the start of the infection.
An adenocarcinoma that arises from the endocervix. It is the most common type of endocervical adenocarcinoma. The neoplastic epithelium shows a pseudostratified architecture and the malignant cells have enlarged, elongated, and hyperchromatic nuclei.
A response indicating that 11 to 20 hours were spent on an activity.
A response indicating that 11 or more hours were spent on an activity.
Replacement of the endocervical epithelium with benign-appearing prostatic glands.
A response indicating a usual walking pace that is easy or casual, less than 2 mph.
Prosthetic valve endocarditis that occurs days to weeks after surgery.
A cytogenetic abnormality that refers to a translocation involving the EWSR1 gene.
A change in the nucleotide sequence of the EPCAM gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 21 of the EGFR gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 20 of the EGFR gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 19 of the EGFR gene.
In-frame deletions occurring within the exon 19-encoded part of the epidermal growth factor receptor (EGFR) kinase domain. These mutations are commonly seen in non-small cell lung cancer and are associated with increased sensitivity to EGFR tyrosine kinase inhibitors.
A molecular genetic abnormality indicating the presence of a mutation in exon 18 of the EGFR gene.
A nanocell formulation targeting the epidermal growth factor receptor (EGFR) using bispecific antibodies (bsAb) against EGFR and containing the antineoplastic anthracycline antibiotic doxorubicin, with potential antineoplastic activity. Upon administration of doxorubicin-loaded EGFR-targeting nanocells, the nanocells are stable in the bloodstream and the anti-EGFR bsAb moiety targets and binds to EGFR-expressing tumor cells. Upon binding, the nanocell allows for specific delivery of doxorubicin to tumor cells overexpressing EGFR. Upon endocytosis by the tumor cells, the nanocell is broken down and releases doxorubicin, which intercalates into DNA and interferes with topoisomerase II activity, thereby inhibiting DNA replication and RNA synthesis. Compared to doxorubicin alone or liposomal doxorubicin, targeted delivery of doxorubicin improves efficacy while lowering the toxicity profile. EGFR, a tyrosine kinase receptor, is overexpressed in many cancer cell types. The nanocell is a bacterially derived nanosphere; the bacterial components are unlikely to induce an immune response in the immunosuppressed tumor microenvironment.
A response indicating that an individual doesn't know or is not sure whether they smoked a cigarette.
Any mutation of the TP53 gene that results in a nonconservative mutation within the key DNA-binding domain (L2-L3 region) of the p53 protein, or a stop codon in any region.
A finding of disorganized chewing or mashing with solid pieces of bolus unchewed prior to swallowing.
The transmission of an infectious agent from a source (e.g., person, animal, or surface) to a host without an intermediary.
A morphologic finding indicating the presence of dilated cystic spaces in the stroma of a neoplasm.
A finding of diffuse residue following swallowing.
A childhood diffuse midline glioma characterized by the presence of histone H3 K27M mutation.
A benign band-like proliferation of tightly-packed, small to medium sized endocervical glands below the surface of the endocervical canal.
A glioma that has diffusely infiltrated the surrounding central nervous system tissues.
Diffuse astrocytoma lacking mutations in IDH1 or IDH2 genes.
Diffuse astrocytoma carrying IDH mutations.
A response indicating that an individual didn't smoke a cigarette at all.
A change in the nucleotide sequence of the BRCA1 gene that is associated with increased risk of disease.
A finding of delayed initiation of tongue motion during swallowing.
A morphologic finding indicating the presence of a high grade undifferentiated malignant cellular infiltrate and a second component of a low grade malignant cellular infiltrate in a tissue sample.
A nucleotide substitution at position 957 of the coding sequence of the DRD2 gene where cytosine has been mutated to thymine.
A nucleotide insertion of a cytosine between positions -486 and -485 in the 5' promoter region of the DRD2 gene.
A change in the nucleotide sequence of the DRD2 gene.
A change in the nucleotide sequence of the DOCK8 gene.
A condition of decreased or absent presence or activity of dedicator of cytokinesis protein 8. Deficiency of this protein is associated with autosomal recessive hyper-IgE recurrent infection syndrome.
A quadruple mixture composed of the corticosteroid dexamethasone, the aminoglycoside antibiotic gentamicin, the vitamin cyanocobalamin (vitamin B12), and the local anesthetic agent procaine, with antimucositic activity. Upon oral administration of the cyanocobalamin/dexamethasone/gentamicin/procaine formulation, the active ingredients prevent or inhibit inflammation and infection of the oral mucosa and reduce the associated pain. This may prevent or treat radiation-induced oral mucositis (OM).
The qualitative measurement of the severity of a thickening cardiac valve cusp.
The qualitative measurement of the severity of tethering of a cardiac valve cusp.
The qualitative measurement of the severity of restricted motion of a cardiac valve cusp.
The time point during the cardiac cycle when the prolapse of of one or more cusps occurs.
The qualitative measurement of the severity of a prolapsing cardiac valve cusp.
The time point during the cardiac cycle when the flail of one or more cusps occurs.
The qualitative measurement of the severity of a flailing cardiac valve cusp.
The qualitative measurement of the severity of doming of a cardiac cusp.
The cross-sectional thickness of a tissue measured at end ventricular systole.
The cross-sectional thickness of a tissue measured at end ventricular diastole.
The cross sectional diameter measured at mid ventricular systole.
The cross sectional diameter measured at end ventricular systole.
The cross sectional diameter measured at end ventricular diastole.
A rare morphologic variant of papillary thyroid gland carcinoma characterized by the presence of solid, cribriform, and squamoid-morular areas.
The transmission of an infectious agent via touch.
A lesion that demonstrates both cystic and solid components; the solid components can range from thin walls (septae) to a solid tissue mass.
A finding of complete superior movement of thyroid cartilage with complete approximation of arytenoids to epiglottic petiole during swallowing.
A finding of complete pharyngeal clearance following swallowing.
A finding of complete oral clearance after swallowing.
A finding of complete laryngeal vestibular closure; no air/contrast in laryngeal vestibule.
A finding of complete inversion of epiglottis during swallowing.
A finding of complete distension and complete duration of pharyngoesophageal segment opening during swallowing; no obstruction of flow.
A finding of complete anterior movement of hyoid during swallowing.
A score of 0 on a comparative scale that ranges from 3+: Very much better to -3: Very much worse.
A score of -1 on a comparative scale that ranges from 3+: Very much better to -3: Very much worse.
The presence of microorganisms (not contamination) on a body surface, including the skin and mucosal surfaces (e.g., respiratory, gastrointestinal, and urogenital tracts). Colonization implies the lack of signs or symptoms of infection but often precedes infection.
An adenoma that arises from the colon. It is characterized by the presence of severe epithelial dysplasia.
A finding of collection of residue within or on pharyngeal structures following swallowing.
A finding of cohesive bolus between tongue to palatal seal during swallowing.
A measure of drug sensitivity and resistance predictions for bladder cancers based on the COXEN gene expression profile method.
Chronic eosinophilic leukemia characterized by the rearrangement of the PDGFRA gene, most often resulting in the formation of FIP1L1-PDGFRA fusion transcripts.
An on-going Epstein-Barr virus (EBV) infection characterized by repeated infectious mononucleosis-like symptoms, a very high titer of anti-EBV antibodies, and high levels of Epstein-Barr virus nucleic acids. Patients with CAEBV often develop progressive cellular and humoral immunodeficiency with pancytopenia and hypogammaglobulinemia.
An infectious disorder that occurs in childhood.
An ectopic pregnancy implanted in a previous cesarean (hysterotomy) scar, surrounded by myometrium and connective tissue.
A yolk sac tumor that arises from the cervix. Patients present with abnormal vaginal bleeding and a polypoid, friable mass, protruding into the vagina.
A cervical adenocarcinoma characterized by the presence of a prominent villoglandular pattern.
A rare malignant neoplasm with skeletal muscle differentiation arising from the cervix.
A neuroendocrine neoplasm that arises from the cervix. This category includes low grade neuroendocrine tumor, grade 1 (carcinoid tumor), low grade neuroendocrine tumor, grade 2 (atypical carcinoid tumor), and neuroendocrine carcinoma (small cell and large cell neuroendocrine carcinoma).
A cervical mucinous adenocarcinoma showing gastric differentiation.
A benign endocervical gland proliferation characterized by the presence of closely packed glands composed of columnar to cuboidal cells with subnuclear mucin vacuoles. It is associated with progestins or pregnancy.
The presence of embryonic remnants of mesonephric ducts in the cervix and their benign hyperplastic proliferations.
A rare malignant neoplasm with nerve sheath differentiation arising from the cervix.
An extremely rare low grade neuroendocrine tumor that arises from the cervix. It is characterized by the presence of greater degree of nuclear atypia and mitotic activity as compared to low grade neuroendocrine tumor, grade 1.
An extremely rare low grade neuroendocrine tumor that arises from the cervix. It is characterized by the presence of neuroendocrine cells with abundant cytoplasm, granular chromatin, and visible nucleoli arranged in organoid, spindled, or trabecular growth patterns. Significant atypia or increased mitotic activity are not present.
A malignant neoplasm with smooth muscle differentiation arising from the cervix.
An uncommon benign smooth muscle neoplasm that arises from the cervix.
A benign lesion characterized by the presence of endocervical-type glands in the outer half of the cervical wall.
A highly aggressive malignant vascular neoplasm that arises from the cervix and shows endothelial cell differentiation.
A carcinoma that arises from the cervix and is characterized by the presence of a cervical adenocarcinoma variant and a neuroendocrine carcinoma component.
A finding of low concentrations of testosterone in a subject's serum that results from the use of surgical or chemical castration procedures.
The anatomic trajectory of the retrograde blood flow from a cardiac valve.
A malignant neoplasm that affects dogs, arising from transitional epithelium.
A malignant mesenchymal neoplasm that affects dogs. It arises from muscle, fat, fibrous tissue, bone, cartilage, and blood vessels.
A malignant mesenchymal neoplasm arising from skeletal muscle that occurs in dogs.
A malignant epithelial neoplasm arising from the prostate gland of a dog.
A tumor composed of mast cells that occurs in dogs.
A malignant lymphoproliferative disorder that affects dogs. It is characterized by the clonal proliferation of B- or T-lymphocytes in the lymph nodes, bone marrow, and/or extranodal sites.
A carcinoma that arises from the lung in dogs and is characterized by the presence of malignant glandular epithelial cells.
An acute or chronic malignant (clonal) hematologic disorder, arising from hematopoietic stem cells in dogs. It is characterized by the presence of primitive or atypical myeloid or lymphoid cells in the bone marrow and the blood.
A malignant neoplasm that affects dogs, characterized by the presence of malignant cells with morphologic and immunophenotypic characteristics similar to those seen in mature histiocytes.
A malignant tumor arising from hepatocytes that occurs in dogs.
A brain or spinal cord tumor arising from glial cells that occurs in dogs.
GM1-gangliosidosis that occurs in dogs, caused by mutation(s) in the GLB1 gene, encoding beta-galactosidase.
A change in the nucleotide sequence of the CTRC gene.
A score of 9 on the COXEN Sensitivity Scale.
A score of 8 on the COXEN Sensitivity Scale.
A score of 7 on the COXEN Sensitivity Scale.
A score of 6 on the COXEN Sensitivity Scale.
A score of 5 on the COXEN Sensitivity Scale.
A score of 40 on the COXEN Sensitivity Scale.
A score of 3 on the COXEN Sensitivity Scale.
A score of 39 on the COXEN Sensitivity Scale.
A score of 38 on the COXEN Sensitivity Scale.
A score of 37 on the COXEN Sensitivity Scale.
A score of 36 on the COXEN Sensitivity Scale.
A score of 35 on the COXEN Sensitivity Scale.
A score of 34 on the COXEN Sensitivity Scale.
A score of 33 on the COXEN Sensitivity Scale.
A score of 32 on the COXEN Sensitivity Scale.
A score of 31 on the COXEN Sensitivity Scale.
A score of 2 on the COXEN Sensitivity Scale.
A score of 29 on the COXEN Sensitivity Scale.
A score of 28 on the COXEN Sensitivity Scale.
A score of 27 on the COXEN Sensitivity Scale.
A score of 26 on the COXEN Sensitivity Scale.
A score of 25 on the COXEN Sensitivity Scale.
A score of 24 on the COXEN Sensitivity Scale.
A score of 23 on the COXEN Sensitivity Scale.
A score of 22 on the COXEN Sensitivity Scale.
A score of 21 on the COXEN Sensitivity Scale.
A score of 20 on the COXEN Sensitivity Scale.
A score of 1 on the COXEN Sensitivity Scale.
A score of 19 on the COXEN Sensitivity Scale.
A score of 18 on the COXEN Sensitivity Scale.
A score of 17 on the COXEN Sensitivity Scale.
A score of 16 on the COXEN Sensitivity Scale.
A score of 14 on the COXEN Sensitivity Scale.
A score of 13 on the COXEN Sensitivity Scale.
A score of 12 on the COXEN Sensitivity Scale.
A score of 11 on the COXEN Sensitivity Scale.
A score of 10 on the COXEN Sensitivity Scale.
An epigenetic modification involving methylation of CpG islands in the promoter region of the CHFR gene.
A change in the nucleotide sequence of the CDKN2A gene.
A change in the nucleotide sequence of the CALR gene.
Expression of a fusion protein that results from the fusion of RELA and C11orf95 genes. It is present in the majority of supratentorial ependymomas in children.
A non-invasive, precancerous lesion in the bronchial epithelium. Depending on the morphologic features it is classified as columnar cell dysplasia, basal cell dysplasia, squamous dysplasia, or bronchial epithelial dysplasia with transitional differentiation.
A rare serous cystadenoma arising from the broad ligament.
A rare serous cystadenofibroma arising from the broad ligament.
A rare serous adenocarcinoma that arises from the broad ligament.
A response indicating a usual walking pace that is brisk, 3-3.9 mph.
A finding of brisk tongue motion during swallowing.
Instances where blood pressure is outside of established parameters.
A finding of bilateral bulging on pharyngeal contraction during swallowing.
A proprietary plasmid DNA expression vector encoding bi-functional short hairpin RNAs (bi-shRNAs) targeting the identical type 1 translocation junction region of the human fusion oncogene Ewing sarcoma (EWS)/Ets family transcription factor Friend leukemia virus integration 1 (FLI1) and are encapsulated in liposomal delivery vehicle (lipoplex; LPX), with potential antineoplastic activity. pbi-shRNA EWS/FLI1 type 1 contains 2 stem-loop structures encoded by a plasmid vector: one cleavage-dependent unit with perfectly matched passenger- and guide-strand, which is the small interfering RNA (siRNA)-like component, and one cleavage-independent unit composed of a strategically mismatched double strand, which is the microRNA (miRNA)-like component. Upon intratumoral administration and transcription into tumor cells, one shRNA unit with an imperfectly matched sequence causes inhibition of EWS/FLI1 messenger RNA (mRNA) translation (through mRNA sequestration and cleavage-independent degradation) while the other unit with a perfectly matched sequence promotes EWS/FLI1 mRNA degradation (through cleavage-dependent mRNA silencing). This prevents EWS/FLI1 expression in tumor cells, which results in a reduction of tumor cell proliferation. The EWS/FLI1 type 1 fusion gene product is overexpressed in type 1 Ewing's sarcoma and correlates with increased tumor proliferation and poor prognosis.
A benign neoplasm with perivascular epithelioid cell differentiation arising from the uterine corpus. It is characterized by the absence of pleomorphism and scarcity or absence of mitotic figures. It usually affects perimenopausal women. Patients present with a pelvic mass or abnormal bleeding.
A rare benign mesenchymal neoplasm that arises from the cervix.
A preparation of autologous Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocytes (CTLs), which have specific reactivity to the EBV antigens, latent membrane proteins (LMP) 1 (LMP1) and 2 (LMP2), EBV nuclear antigen (EBNA) and BamHI-A rightward frame-1 (BARF1), with potential immunomodulating and antineoplastic activities. Upon administration, baltaleucel-T targets and binds to EBV-expressing cancer cells specifically expressing the targeted antigens. This may kill LMP1/LMP2/EBNA/BARF1-expressing EBV-associated cancer cells. LMP1, LMP2, EBNA and BARF1 are tumor-associated antigens (TAAs) that are specifically associated with EBV infection, and play key roles in the proliferation of a variety of tumors.
A multiple electrolyte, isotonic, crystalloid solution for intravenous infusion containing sodium chloride, sodium gluconate, sodium acetate, potassium chloride and magnesium chloride, which can restore electrolyte balance, normalize pH, and provide hydration. Upon intravenous administration, the balanced crystalloid solution will replace lost body fluids and electrolytes thereby providing hydration, normalizing electrolyte concentrations and regulating acid-base balance.
A vaccine containing bacillus Calmette-Guerin (BCG), a live, attenuated strain of Mycobacterium bovis obtained from the Pasteur Institute in 1924, with non-specific immunoadjuvant and immunotherapeutic activities. Upon intradermal administration, BCG Tokyo-172 strain vaccine activates the immune system and enhances a specific, systemic BCG antigen immune response. This results in active immunization against tuberculosis and primes the immune system against future administered BCG antigens.
A solution containing an attenuated, live culture preparation of the bacillus Calmette-Guerin (BCG) strain of Mycobacterium bovis obtained from the Pasteur Institute in 1924, with potential immunostimulating and antineoplastic activities. Although the precise mechanism of action is unknown, upon intravesical instillation through a catheter, the attenuated, live BCG bacteria in the BCG Tokyo-172 strain solution come into direct contact with the bladder wall and elicits a local, multifaceted immune response against the BCG antigens, which kills the bladder cancer cells. Previous vaccination with a systemic BCG vaccine may enhance the immune system's response against the BCG antigens.
A change in the nucleotide sequence of the BAP1 gene.
A precursor B acute lymphoblastic leukemia (B-ALL) which does not have the cytogenetic abnormality t(9;22)(q34;q11.2). Most cases of ALL do not have this translocation.
A dendritic cell (DC)-based cancer vaccine composed of autologous DCs pulsed with specific tumor-associated peptide antigens (TAPA), with potential immunostimulatory and antineoplastic activities. Upon administration, autologous TAPA-pulsed DC vaccine exposes the immune system to the specific TAPAs, which may result in cytotoxic T-lymphocyte (CTL)-mediated immune responses against the TAPA-expressing cancer cells. This leads to cancer cell lysis. This vaccine is specific towards peptides derived from the following proteins: sperm autoantigenic protein 17 (SP17), ropporin, A-kinase anchor protein 4 (AKAP4), pituitary tumor-transforming 1 (PTTG1) and SPANX family member B (SPANX-B).
A cell-based cancer vaccine composed of autologous dendritic cells (DCs) pulsed with a cell lysate from an autologous neuroblastoma containing tumor-associated antigens (TAAs) and the immunostimulant keyhole limpet hemocyanin (KLH), with potential immunostimulatory and antineoplastic activities. Upon administration, autologous neuroblastoma lysate/KLH-pulsed DC vaccine may stimulate the immune system to mount an anti-tumoral cytotoxic T-lymphocyte (CTL) response against neuroblastoma cells, which may result in tumor cell lysis. KLH is an immunogenic carrier and serves as an immunostimulant to improve antigenic immune recognition and T-cell responses.
A preparation of human autologous T-lymphocytes transduced with a viral vector encoding for a T-cell receptor (TCR) specific for a human hepatitis B virus (HBV) surface antigen (HBsAg), with potential antineoplastic activity. Following administration, the autologous HBV antigen specific TCR-redirected autologous T-lymphocytes recognize and bind to the HBV antigen-positive cells, which induces cytotoxic T-lymphocyte (CTL)-mediated elimination of HBV antigen-positive cancer cells. HBV antigens are found on HBV-positive cells and HPV-induced hepatocellular carcinoma (HCC).
A precancerous lesion characterized by the presence of atypical glandular epithelial features in foci of endometriosis. Atypical endometriosis has been observed in contiguity with carcinomas.
The 2-dimensional surface enclosed within a boundary and measured at end ventricular systole.
The 2-dimensional surface enclosed within a boundary and measured at end ventricular diastole.
A capsule containing the dimesylate salt form of apilimod, an inhibitor of the class III PI kinase phosphatidylinositol-3-phosphate 5-kinase (PIKfyve), with potential antineoplastic and immunomodulatory activities. Upon oral administration of apilimod dimesylate capsule, apilimod selectively binds to and inhibits PIKfyve. The inhibition leads to disruption of PIKfyve-mediated signal transduction pathways and eventually inhibits tumor cell growth in PIKfyve-overexpressing tumor cells. Also, PIKfyve inhibition by apilimod inhibits the toll-like receptor (TLR)-induced production of various cytokines, including interleukin-12 (IL-12) and IL-23, thereby preventing IL-12/IL-23-mediated immune responses. PIKfyve, a lipid kinase dysregulated in various tumor types, plays a key role in TLR signaling and tumor cell migration, proliferation and survival.
The width of the vena contracta of the aortic valve.
The area of the vena contracta of the aortic valve.
The measured width of the backflow of blood into the left ventricular outflow tract.
A relative measurement (ratio or percentage) of the aortic regurgitant jet width to left ventricular outflow tract diameter.
A monoclonal antibody directed against programmed cell death protein 1 (PD-1; PD1; CD279).
Any monoclonal antibody directed against the antigen glucocorticoid-induced TNFR-related protein (GITR; tumor necrosis factor receptor superfamily member 18 (TNFRSF18).
The maximum rate of the annular motion during late diastole (active ventricular filling).
An anaplastic oligodendroglioma carrying IDH gene family mutation and combined whole-arm losses of 1p and 19q (1p/19q codeletion).
Anaplastic astrocytoma lacking mutations in IDH1 or IDH2 genes.
Anaplastic astrocytoma carrying IDH mutations.
The histopathological evaluation of staining in tissue based on the Allred scoring system (Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998 Feb;11(2):155-68).
A score developed by Allred et al. (1998) for the proportion of tumor cells that are positive for a given biomarker. The proportion score is assigned based on the biomarker positivity measurement.
A score developed by Allred et al. (1998) for the average staining intensity for all stained protein-positive cells.
An autosomal recessive condition due to mutation(s) in the CYP11B2 gene that results in decreased activity of mitochondrial cytochrome P450 11B2 with reduced aldosterone synthesis and salt wasting.
Aldosterone synthase deficiency characterized by decreased conversion of 18-hydroxycorticosterone to aldosterone.
Aldosterone synthase deficiency characterized by decreased conversion of corticosterone to 18-hydroxycorticosterone.
A rare form of botulism that occurs among adults by the same mechanism as infant botulism.
A disorder characterized by abnormal inflammation of various tissues, particularly the blood vessels, with intermittent. fevers, areas of net-like, mottled skin discoloration (livedo racemosa), hepatosplenomegaly, and recurrent strokes.
A cell-based cancer vaccine containing autologous dendritic cells (DCs) that are transduced with a replication-deficient adenovirus type 5 vector (Ad5) encoding a mutated form of the tumor-associated antigen (TAA) survivin, with potential immunostimulatory and antineoplastic activities. Upon administration, Ad5-survivin-transduced autologous DC vaccine may elicit an immune response against cancer cells expressing survivin by activating cytotoxic T-cells (CTLs). This leads to an induction of cell death in survivin-positive tumor cells. Survivin, a member of the inhibitor of apoptosis (IAP) family of proteins, may be upregulated in certain tumor cell types and plays a key role in tumor cell growth and survival.
Acute myeloid leukemia characterized by the presence of a FLT3-internal tandem duplication (ITD) mutation. Patients with this mutation usually present with more aggressive disease and have higher rates of relapse after remission.
An acute onset of focal limb weakness that is associated mainly with gray matter abnormalities or CSF pleocytosis, but which is without an apparent cause.
A mutation in a RAS family gene (HRAS, KRAS or NRAS) that causes the encoded GTPase to be resistant to GTP hydrolysis and results in constitutive activation of its activity and downstream pathways.
A change in the nucleotide sequence of any one of the genes encoding proteins in the phosphatidylinositol 3-kinase (PI3K) family that results in constitutive PI3K activity and aberrant activation of PI3K-dependent signaling pathways.
A finding of one kidney after the loss of the second, whether due to injury, disease or surgery.
Inflammatory myofibroblastic tumor that arises from the abdominal cavity.
A response indicating that an individual is or was a little tired.
A response indicating that an individual is or was a little short of breath.
A response indicating that an individual has or had a little energy.
A subjective response indicating that something is or was a fair amount.
Ovotesticular differences of sex development in individuals with 46,XY/46,XX mosaic karyotype.
The presence of ovarian and testicular tissue in the an individual with 46,XX karyotype. The anatomical expression of this condition is variable.
Deterioration of enteric neurons with impairment of enteric neuronal structure. Typical neuropathological findings include qualitative (e.g., neuronal swelling, intranuclear inclusions, axonal degeneration) and quantitative (e.g., reduction in the number of neurons) abnormalities of the enteric neurons.
An abnormality of the enteric nervous system, which comprises two types of ganglia, the myenteric (Auerbach's) and submucosal (Meissner's) plexuses. The enteric nervous system functions to control gut movement, fluid exchange between the gut and its lumen, and local blood flow. [HPO:probinson]
Folds of membranous tissue (peritoneum, mesothelium) attached to the wall of the abdomen and enclosing viscera. Examples include the mesentery for the small intestine; the transverse mesocolon, which attaches the transverse portion of the colon to the back wall of the abdomen; and the mesosigmoid, which enfolds the sigmoid portion of the colon. Cells of the same embryologic origin also surround the other organs of the body such as the lungs (pleura) or the heart (pericardium).
Marked rugae formation of the skin of the labia majora.
A type of primitive reflex that is elicited by repetitive tapping on the forehead. Normal subjects usually blink in response to the first several taps, but if blinking persists, the response is abnormal and considered to be a sign of frontal release. Persistent blinking is also known as Myerson's sign.
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased sensation of itching over the skin of the breast.
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased sensation of itching over the skin of the hand.
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased sensation of itching over the skin of the abdomen.
No fall in mean pulmonary arterial pressure (mPAP) falls by at least 10 mmHg to an absolute value less than 40 mmHg without a degradation in cardiac output (CO) in response to a short-acting vasoactive agent such as adenosine, epoprostenol, or inhaled nitric oxide.
Pulmonary vasodilator testing is performed during right-heart catheterization and involves a short-acting vasoactive agent such as adenosine, epoprostenol, or inhaled nitric oxide. The current definition of a normal (positive) response is a drop in mean pulmonary artery pressure of at least 10 mm Hg (or 20 percent) to below 40 mm Hg.
Areas of brighter than expected signal on magnetic resonance imaging emanating from locations distant from the ventricular system.
Areas of brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter that surrounds the cerebral ventricles.
Substantially shortened length of the small intestine as a result of a developmental defect.
Anomalous form of the proerythroblast, i.e., the immature, nucleated erythrocyte occupying the stage of erythropoeisis that follows formation of erythroid progenitor cells. This cell is CD71-positive, has both a nucleus and a nucleolus, and lacks hematopoeitic lineage markers.
Abnormal form of the progenitor cells committed to the erythroid lineage.
A structural anomaly of the digestive system.
A functional anomaly of the digestive system.
A structural anomaly of nerves of the enteric nervous system.
Rectovestibular fistula with a normal anus is known as H-type fistula or double termination of the alimentary tract.
A congenital malformation characterized by an abnormal connection (fistula) between the rectum and the vulval vestibule, at the lower aspect of the vaginal opening.
An increased concentration of prostate specific antigen (PSA) in the circulation.
A functional anomaly of the tiny blood vessels that connect arterioles with venules and whose walls act as semipermeable membranes that mediate the diffusion of fluids and gases between the blood circulation and body tissues.
A structural anomaly of the tiny blood vessels that connect arterioles with venules and whose walls act as semipermeable membranes that mediate the diffusion of fluids and gases between the blood circulation and body tissues.
Small, hard cyst-like nodules, freely moveable in the subcutis over the bony prominences of the legs and arms, which have an outer calcified layer with a translucent core on x-ray.
Diffusely widened perivascular spaces in the basal ganglia, affecting especially the corpus striatum. Status cribrosum is usually symmetrical, with the perivascular spaces showing CSF signal and without diffusion restriction. The word cribriform means sievelike, with multiple perforations.
Partial or complete loss of foveal tissue that was once present.
The upper incisors deviate from the normal angle of being roughly parallel to the surface of the face and instead slant outwards.
Downward movement of the trachea during inspiration due to downward traction on the tracheobronchial tree.
An abnormal anatomic position of the fovea, the small, central pit composed of closely packed cones that is located in the macula of the retina.
A structural anomaly of the capillary blood vessels in the renal glomerulus.
Widening of the wall of capillary blood vessels in the glomerulus. This feature may be produced by deposits and other changes affecting either subepithelial and subendothelial regions or the glomerular basement membrane itself.
Repeated episodes of headache with rapid onset, reaching a peak within minutes and of short duration (less than one hour) with pain that is throbbing, pulsating, or bursting in quality. [HPO:probinson]
Deleterious experiences in first 18 years of life.
A rare genetic intestinal disease with the presence of multiple (usually large) hyperplastic/serrated colorectal polyps, usually with a pancolonic distribution. Histology reveals hyperplastic polyps, sessile serrated adenomas (most common), traditional serrated adenomas or mixed polyps. It is associated with an increased personal and familial (first-degree relatives) risk of colorectal cancer. There is evidence this disease is caused by heterozygous mutation in the RNF43 gene on chromosome 17q22.
An orally available small molecule, mutant-selective inhibitor of epidermal growth factor receptor (EGFR) with potential antineoplastic activity. Olmutinib binds to and inhibits mutant forms of EGFR, thereby leading to cell death of EGFR-expressing tumor cells. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit the EGFR wild type form.
Meets clinical case definition and has supportive or presumptive laboratory results that are consistent with the diagnosis, yet do not meet the criteria for laboratory confirmation.
Meets clinical case definition; signs and symptoms with are consistent or compatible with a particular disease.
Renal papillary necrosis in a patient with type 1 or type 2 diabetes.
Haemolytic uraemic syndrome with either a family history of haemolytic uraemic syndrome or a genetic mutation known to cause haemolytic uraemic syndrome, or both.
A person who habitually uses nicotine, whether by smoking or other delivery system (such as electronic cigarette).
Syndrome with characteristics of microtia with thickened ear lobes, micrognathia and conductive hearing loss due to congenital ossicular anomalies. It has been described in two families. The mode of inheritance is autosomal dominant.
A rare haematological disorder, seen almost exclusively in males, characterised by moderate to severe thrombocytopenia with haemorrhages with or without the presence of mild to severe anaemia. The disease affects mainly males as females are usually asymptomatic or have only mild symptoms. It presents in infancy or in neonates (in severe cases) with patients bruising easily along with further manifestations of thrombocytopenia. The disease is caused by mutations in the GATA1 (Xp11.23) gene encoding GATA1, a transcriptional regulator involved in erythropoiesis and megakaryocytopoiesis. Different mutations found in this gene account for a variable phenotypic spectrum of disorders.
Inherited distal renal tubular acidosis combined with sensorineural deafness.
Syndrome with the association of bilateral macular coloboma, cleft palate, and hallux valgus. It has been described in a brother and sister. Pelvic, limb and digital anomalies were also reported. Transmission is autosomal recessive.
An extremely rare autosomal dominant association reported in a single Swiss family with clinical characteristics of juvenile cataract associated with bilateral microcornea and renal glucosuria without other renal tubular defects.
This syndrome has characteristics of hypoplastic corpus callosum, microcephaly, severe intellectual deficit, preauricular skin tags, camptodactyly, growth retardation, and recurrent bronchopneumonia. It has been described in four patients in two families. Transmission is autosomal recessive.
This syndrome is characterised by anomalies of the lens (ectopia and cataracts) and retina (generalised tapetoretinal dystrophy and total retinal detachment). Myopia has also been reported. It has been described in four members of the same family all resulting from a consanguineous marriage. The mode of transmission is autosomal recessive.
Syndrome with characteristics of intellectual deficit, blindness caused by ocular malformations (microphthalmia, microcornea and sclerocornea), short stature, dysmorphic facial features (narrow nasal bridge and prominent ears), hypotrichosis, and malaligned teeth. It has been described in two siblings (brother and sister) and is likely to be transmitted as an autosomal recessive trait.
A rare subtype of dystrophic epidermolysis bullosa that shows no blistering and that has characteristics of dystrophic or absent nails. Prevalence is unknown. Approximately ten families have been reported to date. However, this variant may be overlooked because of negligible clinical implications. Onset is usually at birth or during infancy. Except from nail involvement, no other cutaneous or extracutaneous symptoms are observed. Nail deformity is often limited to toenails that can appear thickened and shortened. Caused by mutations within the type VII collagen gene (COL7A1). It usually follows an autosomal dominant pattern of inheritance. One family with an autosomal recessive inheritance has also been reported.
A rare skeletal dysplasia with characteristics of anisospondyly and multiple enchondromas in vertebrae and the metaphyseal and diaphyseal parts of long tubular bones, leading to kyphoscoliosis and lower limb asymmetry.
The association of short stature due to mesomelic shortening of the limbs and Madelung deformity with hereditary nephritis. The syndrome was originally described in male and female members from four generations of one large kindred. The females appeared to be more severely affected than the males, with a sex ratio (female to male) of 4:1. The skeletal anomalies closely resembled those of Leri-Weill dyschondrosteosis. The mode of transmission was reported as autosomal dominant.
Syndrome with the association of bilateral Duane anomaly type 3, severe scoliosis of early onset, congenital myopathy with hypotonia without muscular weakness, delayed motor development, and short stature. It has been described in one pair of siblings. The Duane type 3 anomaly consists of eye abduction and adduction palsy, globe retraction and narrowing of the palpebral fissure. Muscular biopsy shows aspecific myopathy. Intellectual development is normal. The syndrome is most likely inherited in an autosomal recessive manner.
Distal trisomy of the short arm of chromosome 6 has characteristics of pre and postnatal growth retardation, a pattern of specific facial features (mostly of the eyes), microcephaly, and developmental delay. The duplicated region almost always includes 6pter, with proximal breakpoints ranging from 6p21 to 6p25. Interstitial duplications of 6p have also been reported with different phenotypes depending on their size and location. Most cases of distal trisomy 6p result from missegregation of a familial balanced translocation, or pericentric inversion, and are accompanied by another chromosomal imbalance. Intrachromosomal duplications or de novo translocations are also observed.
A rare congenital urogenital anomaly characterised by the presence of double uterus (didelphys, bicornuate or septum-complete or partial), unilateral cervico-vaginal obstruction and ipsilateral renal anomalies (renal agenesis and/or other urinary tract anomalies). Patients are usually diagnosed at puberty after menarche due to recurrent severe dysmenorrhoea, chronic pelvic pain, excessive foul smelling mucopurulent discharge, spotting and intermenstrual bleeding (depending on the existence of uterine or vaginal communications). Fever, dyspareunia, and a palpable abdominal, pelvic or vaginal mass (mucocolpos or pyocolpos) may also be present.
Syndrome with the association of skin mastocytosis (appearing as diffuse pigmentation), short stature, microcephaly, conductive hearing loss, and dysmorphic features. It has been described in only two (female) cases: one with normal mental development born to consanguineous parents and the other with severe psychomotor retardation born to unrelated parents.
An extremely rare autosomal recessive disorder with characteristics of bilateral facial palsy with masked facies, sensorineural hearing loss, dysmorphic features (midfacial retrusion, low-set ears) and strabismus.
A rare disorder characterised by the combination of autoimmune intestinal disease, epileptic seizures and cerebral calcifications. Coeliac disease and epilepsy manifest at a variable age. Coeliac disease can present in a typical form with onset in the first 2 years of life. Coeliac disease may also present in silent or latent forms, which are characterised in the absence of gastrointestinal symptoms, by dermatitis herpetiformis, dental enamel defects or autoimmune thyroiditis. Epilepsy onset is between infancy and adulthood. Most patients present with occipital epileptic seizures, the course being highly variable, with benign, drug-resistant, or epileptic encephalopathy forms. It is not known if epilepsy and/or cerebral calcifications are a consequence of coeliac disease. This syndrome is associated with the HLA-DQ2 and HLA-DQ8 genes.
Congenital nephrotic syndrome with evidence of diffuse mesangial sclerosis on histology or with DNA evidence of a genetic mutation associated with diffuse mesangial sclerosis.
Neurodisability describes a group of congenital or acquired long-term conditions that are attributed to impairment of the brain and/or neuromuscular system and create functional limitations.
Syndrome with the association of Charcot-Marie-Tooth disease and nephropathy. So far, around 15 cases have been described. All patients had proteinuria at onset and some patients presented with nephrotic syndrome. In the majority of cases, pathological studies revealed glomerulosclerosis. Caused by heterozygous mutation in the INF2 gene on chromosome 14q32.
A polymorphic disorder with characteristics of ataxia, sensorineural deafness and narcolepsy with cataplexy and dementia. Disease onset occurs in adulthood from the ages of 30-40. Mild brain atrophy with cerebellum involvement is visible with magnetic resonance imaging. Caused by a mutation in the DNA methyltransferase (DNMT1) gene located on chromosome 19p13.2. It encodes an enzyme essential for the repression of transcriptional activity in numerous postmitotic cells.
A form of amyloidosis with characteristics of the accumulation and extensive visceral deposition of beta 2 microglobulin leading to progressive gastrointestinal dysfunction, Sjögren syndrome and autonomic neuropathy.
A rare genetic disorder with characteristics of lymphadenopathy and/or splenomegaly and recurrent infections due to herpes viruses. Prevalence of this disorder is not known. It is extremely rare with four individuals in one family identified to date. Development is reported to be normal in affected patients. Clinical signs include lymphadenopathy and splenomegaly, and development of recurrent sinopulmonary and significant mucocutaneous infections with the Herpes zoster and Herpes simplex viruses. The disorder is caused by germline homozygous mutations in the CASP8 gene (2q33-q34) involved in the execution phase of cell apoptosis. Carriers with a normal copy of the gene are asymptomatic. Biologically this syndrome has manifestations of slightly elevated double-negative T cells (DNTs) and defective Fas-mediated apoptosis of B, T, and NK lymphocytes. The pattern of inheritance appears to be autosomal recessive.
An extremely rare autosomal dominant immunological disorder with characteristics of variable enteropathy, endocrine disorders (e.g. type 1 diabetes mellitus, hypothyroidism), immune dysregulation with pulmonary and blood-borne bacterial infections and fungal infections (chronic mucocutaneous candidiasis) developing in infancy. Other manifestations include short stature, eczema, hepatosplenomegaly, delayed puberty and osteoporosis/osteopenia.
Syndrome marked by the presence of a unilateral angioma on the face and autistic developmental problems with characteristics of language delay and atypical social interactions. So far, the syndrome has been described in four children.
Syndrome with a combination of symmetric severe distal limb reduction deficiencies affecting all four limbs (oligodactyly), microretrognathia, and microstomia with or without cleft palate. It has been reported in four patients; two of them were siblings and had moderate intellectual deficiency. Two non-related subjects also had severe myopia, bilateral conductive hearing loss and a renal change, referred to as oligomeganephronia, or renal hypoplasia. A 10q24 duplication or triplication was detected in all these patients, similar to the duplication detected in an isolated form of split hand foot malformation.
This syndrome has characteristics of auricular abnormalities and cleft lip with or without cleft palate. Only two cases have been reported in the literature. One of these cases also presented with myopia, nystagmus and retinal pigment abnormalities.
A very rare dysmorphic disorder with characteristics of hypoplasia and coloboma of the alar cartilages and telecanthus described in 2 sisters. No new cases with similar features have been reported since 1976.
An extremely rare and fatal association syndrome with characteristics of absence of the mandible, cerebral malformations with facial anomalies related to a defect in cleavage in the embryonic brain (e.g. synophthalmia, malformed and low-set ears fused in midline, agenesis of the olfactory bulbs, microstomia, hypoglossia/aglossia) and situs inversus partialis or totalis.
A developmental anomaly syndrome with characteristics of coloboma of the iris and optic nerve, facial dysmorphism (high forehead, micro retrognathia, low-set ears) intellectual deficit, agenesis of the corpus callosum, sensorineural hearing loss, skeletal anomalies and short stature. Caused by mutation in the IGBP1 gene.
This syndrome combines agammaglobulinaemia with marked microcephaly, significant developmental delay, craniosynostosis, a severe dermatitis, cleft palate, narrowing of the choana and blepharophimosis. It has been described in three siblings, two males and one female, born to nonconsanguineous parents. Transmission is probably autosomal recessive. It has been suggested that this syndrome represents a new form of agammaglobulinaemia due to a defect in early B-cell maturation.
Congenital nephrotic syndrome with evidence of an underlying congenital infection (e.g. syphilis, toxoplasmosis, rubella, hepatitis B).
This syndrome has characteristics of X-linked mental retardation, microcephaly, optical atrophy with impaired vision or blindness, a severe hearing defect, facial dysmorphology, spasticity, epileptic seizures and restricted joint movement. It has been described in seven children from two generations of a Swedish family. All patients died in during early childhood.
An extremely rare mitochondrial respiratory chain disease resulting in a neurodegenerative disorder with characteristics of psychomotor delay, hypotonia, areflexia, muscle weakness and wasting in the two patients reported to date. Combined oxidative phosphorylation deficiency-6 (COXPD6) is caused by hemizygous mutation in the AIFM1 gene on chromosome Xq26.1.
A very rare heart-hand syndrome that has characteristics of a variety of cardiovascular anomalies including patent arterial duct, bicuspid aortic valve and pseudocoarctation of the aorta in conjunction with hand anomalies such as brachydactyly and ulnar ray derivative i.e. fifth metacarpal hypoplasia. Transmission is most likely autosomal dominant although X-linked dominance could not be excluded.
This syndrome is characterised by exocrine pancreatic insufficiency, dyserythropoietic anaemia, and calvarial hyperostosis. It has been described in four children, three boys and one girl, from two consanguineous families. The disease is due to a mutation in the COX4I2 gene, encoding a mitochondrial cytochrome C oxidase sub-unit. Transmission is autosomal recessive.
This syndrome has characteristics of sex reversal in males with a 46, XX (SRY-negative) karyotype, palmoplantar hyperkeratosis and a predisposition to squamous cell carcinoma. To date, five cases (four of whom were brothers) have been described.
A status of immunization which is suboptimal for a person.
Chronic kidney disease associated with chronic infection.
Chronic kidney disease developing as a result of removal of kidney tissue (including partial nephrectomy and radical nephrectomy) for the treatment of renal tumor.
Focal and segmental glomerulosclerosis in a patient with sickle cell disease.
Focal and segmental glomerulosclerosis in association with long-term treatment with lithium carbonate, after exclusion of alternative causes.
This syndrome has characteristics of tall stature, learning difficulties and facial dysmorphism. So far, it has been described in six families. The syndrome is caused by mutations in the RNF135 (ring finger protein 135) gene.
Glomerulonephritis with electron dense deposits in the glomerular baseement membrane, associated with treatment with a drug known to be associated with membranous nephropathy and after exclusion of alternative causes.
This syndrome has characteristics of sclerosing bone dysplasia, ichthyosis vulgaris and premature ovarian failure. The bone disorder affects all metaphyseal-diaphyseal regions of the long bones, the skull, and the metacarpals. It has been described in three adult sisters presenting with swelling of the limbs and occasional mild pain in the legs.
Syndrome with characteristics of osteosclerosis, developmental delay and craniosynostosis. It has been reported in 13 patients from a four-generation family. Osteosclerosis was constant and most pronounced in the cranial base and calvarium. Craniosynostosis was reported in four patients and a mild developmental delay in three patients. Dysmorphic features were constant and included macrocephaly, brachycephaly, wide and high forehead, hypertelorism, prominent cheekbones and prominent jaw. A missense mutation A214T in the low-density lipoprotein receptor related protein 5 gene.
This syndrome has characteristics of severe hypertelorism, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, osteopenia with frequent fractures, severe myopia, mild to moderate sensorineural hearing loss and mild intellectual deficit. It has been described in two brothers born to first-cousin parents. No chromosomal anomalies were detected. Transmission appears to be autosomal recessive or X-linked.
This syndrome has characteristics of osteogenesis imperfecta, wormian bones, optic atrophy, retinopathy, seizures and severe developmental delay. It has been described in two siblings born to consanguineous parents.
This syndrome has characteristics of severe dwarfism, progressive scoliosis and bilateral dislocation of the hip, associated with sensorineural deafness and retinitis pigmentosa. Radiographs show diffuse osteoporosis, severe bone-age delay and dysplasia of the femoral head. It has been described in two patients. Transmission is autosomal dominant variable penetrance.
This syndrome has characteristics of hypomineralisation of the cranial bones, thoracic dystrophy, hypotonia and abnormal and slender long bones due to an alteration in remodelling during ossification. It has been described in two brothers and was present at birth. The surviving boy displayed progressive osteopenia, slow healing of the periostal anomalies, hepatic angiomas, a thoracic deformity, delayed tooth eruption, progressive microcephaly with dilation of the cerebral ventricles and mental and motor delay.
Syndrome with characteristics of tongue lobulation, hypoplasia of the epiglottis, median cleft upper lip, broad or bifid nasal tip, hypertelorism or telecanthus, bilateral preaxial and postaxial polydactyly, abnormal tibia and/or radius, duplication of the halluces, short stature and mild intellectual deficit. The syndrome has been described in one family with four affected males in three generations. Increased susceptibility to respiratory infections has been noted. X-linked recessive transmission has been suggested, but the causative gene has not yet been identified.
Chronic kidney disease developing de novo in a person who has previously donated a kidney for the purposes of kidney transplanataion.
Pre-renal acute kidney injury caused by reduction in circulating blood volume, distinct from other potential causes of pre-renal acute kidney injury, e.g. sepsis, decreased arterial blood pressure.
Acute kidney injury caused by heart failure. Also known as Cardiorenal syndrome type 1.
Potential complication following surgery
Obstructive nephropathy which has developed in a patient with bladder cancer.
Glomerulonephritis with electron dense deposits in the glomerular baseement membrane in a patient with cancer, after exclusion of other possible causes of membranous glomerulonephritis.
Renal papillary necrosis in a patient with sickle cell disease or sickle cell trait.
Obstructive nephropathy which has developed in a patient with evidence of prostatic carcinoma.
Obstructive nephropathy which has developed in a patient with evidence of bladder outflow obstruction caused by benign prostatic hypertrophy.
Obstructive nephropathy which has developed in a patient with a history of spinal cord injury or disease.
A rare non-progressive form of cone photoreceptor dysfunction characterised by reduced visual acuity, normal retinal appearance and absent or reduce cone responses on electroretinography but normal colour vision. The syndrome is very rare with only 14 cases reported in the literature so far. The causative gene has not been identified. The reason for the presence of normal colour vision despite the reduced visual acuity and electrophysiological evidence of severe cone dysfunction is uncertain. It has been proposed that patients may have reduced numbers of normal functioning cones with preservation of the three cone types in normal proportions thereby enabling normal colour vision.
Prohormone convertase-I deficiency is the rarest form of monogenic obesity. The disorder is characterised by severe childhood obesity, hypoadrenalism, reactive hypoglycaemia, and elevated circulating levels of certain prohormones. It has been described in two patients: a 43-year-old woman and a female infant. The disorder is caused by mutations in the gene encoding prohormone convertase-1 (PCSK1, 5q15-q21), an enzyme involved in the processing of POMC, and numerous prohormones including proinsulin.
Syndrome with characteristics of precocious obesity, congenital hypothyroidism, neonatal colitis, cardiac hypertrophy, craniosynostosis and developmental delay. It has been described in two brothers, one of who died within the first month of life. The parents of the two children were nonconsanguineous and in good health however the pregnancies were complicated by maternal HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelets). The mode of inheritance has not yet been clearly established.
This syndrome has characteristics of megalencephaly, polymicrogyria and hydrocephalus with variable polydactyly. It has been described in six unrelated patients. Intellectual deficit or slow development is also present. The mode of inheritance of this syndrome is unknown since all cases were sporadic.
Syndrome with characteristics of hypogonadotropic hypogonadism associated with gonadotropin-releasing hormone (GnRH) deficiency, anosmia or hyposmia (with hypoplasia or aplasia of the olfactory bulbs) and complex congenital cardiac malformations (double-outlet right ventricle, dilated cardiomyopathy, right aortic arch). It represents a distinct clinical entity from Kallmann syndrome. Less than 10 cases have been described so far.
This syndrome has characteristics of severe intellectual deficit, kyphosis with onset in childhood and cataract with onset in late adolescence. The syndrome has been described in three siblings. The two brothers also presented with iris coloboma. Other clinical findings include contractures of large joints, bulbous nose with broad nasal bridge, and thick lips. The disease is linked to the pericentromeric region of chromosome 4. Transmission is autosomal recessive.
A developmental defect that may be asymptomatic or lead to cerebrovascular lesions. It is a rare malformation, with only around hundred cases reported in the literature. When symptoms are present, they are caused by cerebrovascular insufficiency, compression of the brain by vessels that dilate to compensate for the absence of the internal carotid artery, or the presence of an aneurysm. Associated intracranial aneurysms occur in 25 to 35% of patients.
This syndrome has characteristics of prenatal linear growth deficiency, hypertrophied alveolar ridges, redundant nuchal skin, postaxial polydactyly and cryptorchidism. Mullerian duct remnants, lymphangiectasis and renal anomalies are also present. Three cases have been described. A small penis was observed in two of these cases. The syndrome is likely to be an autosomal recessive or X-linked trait. All the reported patients died neonatally of hepatic failure.
This syndrome is characterised by the variable association of a cerebrovascular malformation, foot lymphoedema and primary pulmonary hypertension. It has been described in a woman and four of her children.
A very rare syndrome with characteristics of unilateral complete or partial lung agenesis, congenital cardiac defects and ipsilateral thumb anomalies. It has been described in 7 patients. Cardiac abnormalities are variable and mainly consist of atrial septal defect, anomalous pulmonary venous return or patent ductus arteriosus. Thumb anomalies include triphalangeal, proximally placed, hypoplastic or reduplicated thumb. One patient had a preaxial polydactyly with a rudimentary thumb. Other malformations can be also observed. The affected patients have normal intellectual development.
This syndrome is characterised by immune deficiency, gonadal dysgenesis and fatal lung fibrosis. So far, it has been described in two sisters born to consanguineous parents. Both karyotypes were normal female (46,XX). No genetic anomalies could be identified by comparative genome hybridisation analysis of their genomes or by analysis of genes known to be associated with these types of anomalies.
An extremely rare form of genetic lipodystrophy, reported in 3 patients from one family to date, characterised by generalised congenital lipodystrophy, low birth weight, progressive sensorineural deafness occurring in childhood, intellectual deficit, progressive osteopenia, delayed skeletal maturation, skeletal abnormalities described as slender, undermineralised tubular bones and dense metaphyseal striations in the distal femur, ulna and radius of older patients. Autosomal recessive inheritance has been suggested.
The association of the clinical features present in Robinow syndrome (short stature, mesomelic brachymelia, macrocephaly and hypoplastic genitalia) with anterior chamber cleavage anomalies. It has been described in two sisters and is transmitted as an autosomal recessive trait.
Syndrome with the association of microgastria and limb reduction defect. Most of the 50 cases of congenital microgastria reported in the literature are associated with other multiple congenital anomalies. Isolated congenital microgastria is an extremely rare condition; only three cases have been reported in the literature so far. The clinical manifestations of congenital microgastria depend on the stage at which the embryologic development of the stomach is arrested. The microgastria-limb reduction association is believed to arise as a result of aberrant mesodermal development in the fourth or fifth week of embryonic life. The outcome for most of the reported patients with severe microgastria was either death or extreme malnutrition.
Familial and de novo recurrent Xp11.22-p11.23 microduplication has been recently identified in males and females. To date, twelve patients have been described. All patients show moderate to severe intellectual deficit and speech delay. Seizures, early puberty and lower-extremity anomalies, including pes planus or cavus, fifth toe hypoplasia, and syndactyly, are common. Most affected females show preferential activation of the duplicated X chromosome. Duplications are mediated by nonallelic homologous recombination or Alu-mediated recombination.
This syndrome has characteristics of anophthalmia or microphthalmia, retinal dystrophy, and/or myopia, associated in some cases with cerebral anomalies. It has been described in two families. Polydactyly may also be present. Linkage analysis allowed identification of mutations in the BMP4 gene, which has already been shown to play a role in eye development.
A genetic variant of Mendelian susceptibly to mycobacterial disease with characteristics of a complete deficiency in interferon gamma receptor 2, leading to an undetectable response to interferon gamma and consequently to severe and often fatal infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria. The prevalence is unknown. Only ten children have been identified to date. This disease is caused by mutations in IFNGR2 on chromosome 21q22.1-22.2 which encodes the IFN-gamma receptor signal transducing chain, essential for IFN-gamma mediated immunity. Two clinically indistinguishable forms have been reportedly defined by the presence or absence of protein expression on the cell surface.
Syndrome with the association of hypogonadotropic hypogonadism and frontoparietal alopecia. It has been described in six members (four males and two females) of a consanguineous Lebanese family. In addition to frontoparietal alopecia, the remaining scalp hair was also sparse and axillary and pubic hair was absent. Despite the family history of consanguinity, autosomal dominant inheritance with reduced penetrance was considered as the most likely mode of transmission.
A rare autosomal dominantly inherited disease of childhood characterised by hypoproliferative anaemia, hyperuricaemia and slowly progressing kidney failure due to dysregulation of the renin-angiotensin system.
A very rare multiple congenital abnormality syndrome manifesting from birth with progressive hypertrichosis congenita terminalis (thick scalp hair extending onto the forehead with generalised increased body hair) associated with a typical acromegaloid facial appearance (thick eyebrows, prominent supraorbital ridges, broad nasal bridge, anteverted nares, long and large philtrum, and prominent mouth with full lips) appearing during childhood.
A form of diazoxide-sensitive diffuse hyperinsulinism characterised by hypoglycaemic episodes from the neonatal period, a good clinical response to diazoxide and a probable transient nature of the disease with spontaneous resolution.
A mitochondrial fatty acid oxidation disorder characterised by hyperinsulinaemic hypoglycaemia with seizures, and in one case fulminant hepatic failure. Less than 10 cases have been reported to date. The disease can present in infancy or early childhood. It presents with the manifestations of hyperinsulinaemic hypoglycaemia with vomiting, lethargy and seizures. Complications include coma and sudden death. It has responded well to diazoxide. It is caused by a mutation in the HADH gene (4q22-q26) encoding the SCHAD protein that has a dual function both as an enzyme and an inhibitor of glutamate dehydrogenase. The mode of inheritance is autosomal recessive.
A very rare autosomal dominant form of familial hyperinsulinism characterised clinically in the single reported family by postprandial hypoglycaemia, fasting hyperinsulinaemia, an elevated serum insulin-to-C peptide ratio and a variable age of onset.
A form of diazoxide-sensitive diffuse hyperinsulinism, characterised by transient or persistent hyperinsulinaemic hypoglycaemia in infancy that is responsive to diazoxide, evolving in to maturity-onset diabetes of the young subtype 1 later in life.
Syndrome with the association of congenital hydrocephalus, centripetal obesity, hypogonadism, intellectual deficit and short stature. It has been described in two males from one family. An X-linked recessive mode of inheritance was suggested.
A life-threatening disorder, believed to be a cardiovascular clinical variant manifestation of Behcet disease, with the association of multiple pulmonary artery aneurysms and peripheral venous thrombosis. Prevalence is unknown but fewer than 30 cases have been reported in the literature since its first description in 1959 by Hughes and Stovin. Patients (mostly men aged 12-40 years) generally present with the nonspecific signs of pulmonary artery aneurysms, following a history of peripheral venous thrombosis. Other associated signs may include fever and intracranial hypertension. Aneurysms can occur anywhere in the systemic circulation. Recurrent phlebitis also commonly involves the large vessels, resulting in thrombus formation. In general, there is a predisposition for thrombus formation affecting the peripheral veins. It is assumed the disease is a form of vasculitis following a similar mechanism of pathogenesis to that thought to be involved in Behcet disease.
An inborn error of vitamin B12 (cobalamin) metabolism characterised by megaloblastic anaemia, encephalopathy and sometimes, developmental delay, and associated with homocystinuria and hyperhomocysteinemia. There are three types of homocystinuria without methylmalonic aciduria; cblE, cblG and cblD-variant 1 (cblDv1). These disorders are caused by a functional deficiency of the cytoplasmic enzyme methionine synthase (MS), which catalyses remethylation of homocysteine to form methionine.
A fatal malformative disorder with characteristics of Hirschsprung disease, hypoplastic nails, distal limb hypoplasia and minor craniofacial dysmorphic features (flat facies, upward slanting palpebral fissures, narrow philtrum, narrow, high arched palate, micrognathia, low set ears with abnormal helices). Hydronephrosis has also been reported. There have been no further descriptions in the literature since 1988.
This syndrome has characteristics of Hirschsprung disease and absence or hypoplasia of the nails and distal phalanges of the thumbs and great toes (type D brachydactyly). It has been described in four males from one family (two brothers and two maternal uncles). Transmission appears to be X-linked recessive but autosomal dominant inheritance with incomplete penetrance in females cannot be ruled out.
An exceedingly rare form of prion disease with characteristics of neuropathological features of Alzheimer disease including memory impairment and depression, related to abnormal prion protein (PrP) caused by a gene mutation in PRNP. Patients present with a prolonged, atypical course (absence of myoclonus or ataxia) unlike other forms of prion disease, with severe neurofibrillary tangle pathology and high levels of cerebral amyloidosis.
Goossens-Devriendt syndrome has characteristics of intrauterine growth retardation, a congenital heart defect, postaxial polydactyly, brain malformation, abnormal hair with temporal balding and marked facial dysmorphism. It has been reported in two siblings from unrelated parents. One of the siblings died and the surviving patient showed postnatal growth retardation and severe developmental delay.
An infantile-onset neurometabolic disease with characteristics of dystonia, parkinsonism, nonambulation, autonomic dysfunction, developmental delay and mood disturbances. The prevalence is unknown. It has been described in 8 patients from one Saudi Arabian family to date. Caused by a mutation in the SLC18A2 gene (10q25), encoding the vesicular monoamine transporter 2 (VMAT2) which is responsible for the transport of dopamine and serotonin into synaptic vesicles. Mutations in this gene lead to the impairment of VMAT2 and consequently to problems with motor control, autonomic functioning and mood regulation. It is inherited in an autosomal recessive manner.
A very rare multiple congenital anomaly syndrome. The syndrome has characteristics of bifid nose (with bulbous nasal tip but not associated with hypertelorism) with or without the presence of anal defects (i.e. anteriorly placed anus, rectal stenosis or atresia) and renal dysplasia (unilateral or bilateral renal agenesis) and without intellectual disability. BNAR syndrome is phenotypically related to Fraser syndrome and oculotrichoanal syndrome.
This syndrome associates progressive visual loss with scoliosis or kyphoscoliosis and arachnodactyly of the fingers and toes. The syndrome has been described in four patients (three males and one female) from the same family. The male patients presented with the complete phenotype while the female patient suffered only from blindness. No mutations were found in the FBN1, TGFBR1 and TGFBR2 genes that are associated with other syndromes presenting similar clinical findings.
This syndrome has characteristics of bilateral congenital blepharoptosis, ectopia lentis and high myopia. It has been described in three members of one family (in a mother and her two daughters). Transmission appears to be autosomal dominant.
Syndrome with the association of blepharophimosis and ptosis, V-esotropia and weakness of extraocular and frontal muscles, syndactyly of the toes, short stature, prognathism, hypertrophy and fusion of the eyebrows. It has been described in six members of three related families. Transmission is autosomal recessive.
Syndrome with the association of bilateral microtia, severe to profound hearing impairment and cleft palate. It has been described in four individuals from a consanguineous Iranian family. The syndrome is caused by point mutations in the HOXA2 gene, a gene that has already been shown to be involved in development of the auditory system in mice.
An extremely rare form of carbohydrate deficient glycoprotein syndrome with, in the single reported case to date, seizures, some dysmorphic features, axial hypotonia, slight peripheral hypertonia and hyperreflexia.
A phenotypic variant of a group of inherited small vessel disorders known as retinal vasculopathy and cerebral leucodystrophy and characterised by strokes, vision loss, pseudotumours, seizures, motor and sensory deficits, headaches and occasionally renal disease.
A phenotypic variant of a group of inherited small vessel disorders known as retinal vasculopathy and cerebral leucodystrophy and characterised by progressive visual impairment, strokes and often associated with Raynaud phenomenon and migraine-like symptoms.
Syndrome with the association of an axonal sensory and autonomic neuropathy and spastic paraplegia. So far, around nine families have been described in the literature, together with a few sporadic cases. Onset occurs between 1 and 5 years of age with spasticity and progressive severe loss of temperature and pain sensation associated with ulcero-mutilating acropathy. Linkage to chromosome 5q15.31-14.1 was identified in a consanguineous Moroccan family with an autosomal recessive mode of inheritance. Early reports suggested autosomal dominant inheritance but transmission in more recently described families appeared to be autosomal recessive.
This syndrome has characteristics of sensory and autonomic axonal neuropathy, sensorineural hearing loss and persistent global developmental delay. It has been described in four individuals from a consanguineous Lebanese family. Onset occurred in infancy with moderate developmental delay, hypotonia and areflexia. Other less constant findings included weakness, variable dysmorphic features, unsteadiness, and optic atrophy. Transmission appears to be autosomal recessive.
Characterised by the association of type 1 hereditary sensory and autonomic neuropathy with paroxysmal cough and gastrooesophageal reflux. So far, it has been described in two families. Onset occurs in adulthood with distal sensory loss due to an axonal neuropathy, gastrooesophageal reflux, and cough triggered by noxious odours or by pressure in the external auditory canal. The cough may be severe leading to syncope and retinal detachment. Additional features include throat clearing, a hoarse voice, and sensorineural hearing loss. Linkage to chromosome 3p22-p24 was found in both reported families. Transmission is autosomal dominant.
An extremely rare genetic glycogen storage disease reported in one patient to date. Clinical signs included muscle weakness, cardiac arrhythmia associated with accumulation of abnormal storage material in the heart and glycogen depletion in skeletal muscle. Caused by compound heterozygous mutation in the glycogenin 1 (GYG1) gene, which encodes glycogenin-1, on chromosome 3q24.
A disorder belonging to the group of oromandibular-limb hypogenesis syndromes with the presence of an intraoral band of variable thickness attaching the tongue to the hard palate or maxillary alveolar ridge. The syndrome is very rare with less than 30 cases reported in the literature so far. Associated anomalies include cleft palate (in which case the tongue may be attached to the nasal septum), mandibular hypoplasia, upper-lip hypoplasia, hypodontia and variable limb anomalies (oligodactyly, syndactyly and polydactyly as well as more severe limb malformations). The syndrome appears to be sporadic.
This syndrome is characterised by the association of global developmental delay, osteopenia and skin anomalies. To date, only three cases (two brothers and one unrelated girl) have been reported. Central nervous system anomalies manifest as poor language skills, inappropriate behaviour (temper tantrums, aggressiveness), concentration and attention span difficulties and impulsiveness. Intellectual deficit was reported in two out of the three cases. Skin anomalies were hyperkeratosis, granular layer thickening, and sweat gland and melanocyte abnormalities.
A form of combined immunodeficiency characterised by recurrent viral, bacterial, mycobacterial and fungal infections from birth, chronic diarrhoea, pneumonia, meningitis, enteritis, gastrointestinal candidiasis, sepsis and otitis media. All patients present with ectodermal dysplasia that is characterised by hypocalcified amelogenesis imperfecta and leads to the loss of soft dental enamel. In addition, patients present at birth with congenital myopathy, which is characterised by non-progressive generalised muscular dysplasia. Caused by mutations in the ORAI1 and STIM1 genes (12q24 and 11p15.5). Transmission is autosomal recessive.
Syndrome with the association of diffuse palmoplantar keratoderma and acrocyanosis. It has been described in eight members of one family and in two sporadic cases. The mode of inheritance in the familial cases was autosomal dominant.
Syndrome with the association of classical diaphragmatic hernia (Bochdalek type), severe lung hypoplasia and variable associated malformations. It has been reported only once in four successive fetuses (two females and two males) born to a nonconsanguineous couple. The spectrum of malformations is wide and includes omphalocele (one case), severe limb hypoplasia (two cases), syndactyly of the toes (two cases), extra spleen (one case) and an ossification defect of the skull (one case).
This syndrome is characterised by the association of midline malformations, sensory hearing loss, and a delayed-onset generalised dystonia syndrome. It has been described in two monozygotic twins. The syndrome is caused by a missense point mutation in the gene coding for beta-actin, a nonmuscle actin isoform. Mutations in nonmuscle actin isoforms may be associated with developmental anomalies and neurological disorders such as dystonia.
Dermo-odonto dysplasia belongs to the group of tricho-odonto-onychial dysplasia. It has signs of variable severity: dry and thin skin, dental anomalies, nail alteration and trichodysplasia.
Syndrome with the association of dentinogenesis imperfecta, delayed tooth eruption, facial dysmorphism, small stature, sensorineural hearing loss and mild intellectual deficit. It has been described in two brothers born to consanguineous parents. Transmission is autosomal recessive.
A condition characterized by K ATP channel-associated permanent neonatal diabetes mellitus accompanied by neurological manifestations of developmental delay and epilepsy that may be associated with the severity of the mutation(s).
This syndrome has characteristics of severe bilateral deafness, intellectual deficit, umbilical hernia and abnormal dermatoglyphics. It has been described in three males from three generations of one family. Mild facial dysmorphism (telangiectasias, hypertelorism, dental anomalies and a wide nasal root) was also present. Short stature, pancytopenia, microcephaly and renal and genitourinary anomalies were present in some of the patients. The mode of transmission is X-linked recessive and the causative gene is q1-21 region of the X chromosome.
Short stature due to primary acid-labile subunit (ALS) deficiency is characterised by moderate postnatal growth deficit, markedly low circulating levels of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) and hyperinsulinaemia, in the absence of growth hormone (GH) deficiency or GH insensitivity. Less than 10 cases have been reported in the literature so far. It is caused by homozygous inactivating mutations of the ALS gene (IGFALS; 16p13.3). Primary ALS deficiency is inherited in an autosomal recessive manner.
This syndrome has characteristics of short stature, anterior pituitary hormone deficiency, small sella turcica and a hypoplastic anterior hypophysis associated with pointed cerebellar tonsils. It has been described in three generations of large French kindred. Ectopia of the posterior hypophysis was observed in some patients. The syndrome is transmitted as a dominantly inherited trait and is caused by a germline mutation within the LIM-homeobox transcription factor LHX4 gene (1q25).
This syndrome has characteristics of bilateral shortening of the fifth fingers and fifth metacarpals. It has been described in several members of one family. Some members of the family also had spherocytosis and insulin resistance. Transmission is autosomal dominant.
Thoracic insufficiency syndrome is a complex condition involving congenital chest wall deformities that affect normal breathing and lung growth. It results from serious defects affecting the ribs or chest wall, such as severe scoliosis or rib fusion, and various hypoplastic thorax syndromes such as Jeune Syndrome and Jarcho-Levin syndrome.
A genetic variant of Mendelian susceptibility to mycobacterial disease with characteristics of mild bacillus Calmette-Guérin (BCG) infections and recurrent Salmonella infections. The prevalence is unknown. The disease presents in early childhood. BCG is the most common infection encountered, usually after receiving the vaccination. Non-typhoidal Salmonella infections are also seen in half of all cases. Caused by homozygous mutations in the IL12B gene on chromosome 5q31.1-q33.1 which encodes for the IL-12p40 subunit. There are 9 different IL12B mutant alleles identified, including 2 small insertions, 3 small deletions, 2 splice site mutations, 1 large deletion and 1 nonsense mutation.
Syndrome with the association of proximal fusion of the radius and ulna and congenital amegakaryocytic thrombocytopenia. Less than 10 cases have been reported in the literature so far. The syndrome is transmitted as an autosomal dominant trait and is caused by mutations in the HOXA11 gene (7p15).
An extremely rare syndrome described in three members of a family (a mother and her two children) with the association of various ocular abnormalities (partial or complete aniridia, ptosis, pendular nystagmus, corneal pannus, persistent pupillary membrane, lenticular opacities, foveal hypoplasia and low visual acuity) with various systemic anomalies including intellectual disability and obesity in the two children and alopecia, cardiac abnormalities and frequent spontaneous abortion in the mother. There have been no further descriptions in the literature since 1986.
This syndrome is characterised by severe immunodeficiency, osteopetrosis, lymphoedema and anhidrotic ectodermal dysplasia. It has been described in a few unrelated male patients born to mothers with mild incontinentia pigmenti. The first two reported children died before three years of age from multiple infections with Gram-positive cocci, Gram-negative bacilli, mycobacteria, and fungi. The syndrome is classified as a X-linked osteopetrosis and is caused by mutations in the IKBKG (NEMO) gene (Xq28).
Syndrome with characteristics of severe retinal dystrophy marked by visual impairment and profound photophobia without night blindness. Eye examination suggested a cone-rod type of congenital amaurosis. Trichomegaly, bushy eyebrows with synophrys and excessive facial and body hair were also reported. The syndrome has been described in two female cousins both born to consanguineous parents.
This syndrome has characteristics of the association of total alopecia (present at birth), mild intellectual deficit and hypergonadotropic hypogonadism. It has been described in two brothers born to non consanguineous parents of Caucasian origin. Electroencephalogram findings were normal in both cases. Autosomal recessive transmission was considered likely but an X-linked recessive mode of inheritance could not be excluded.
A form of ectodermal dysplasia syndrome with characteristics of short stature of prenatal onset, alopecia, ichthyosis, photophobia, ectrodactyly, seizures, scoliosis, multiple contractures, fusions of various bones, particularly elbows, carpals, metacarpals, and spine, intellectual disability and facial dysmorphism.
An event lasting less than a minute in an infant younger than 1 year of age reported by an observer that is now resolved. Including one or more of the following: cyanosis or pallor; absent, decreased, or irregular breathing; marked change in tone (hypertonia or hypotonia); and altered level of responsiveness. Diagnosed only when there is no explanation for a qualifying event after a history and physical examination and used to evaluate patients who are at lower risk for a subsequent event or serious underlying disorder.
Fibular dimelia accompanied by complete tibial agenesis and mirror polydactyly or foot duplication is a rare developmental anomaly reported in at least 11 cases. It can be isolated or associated with ulnar dimelia, facial abnormalities and sacrococcygeal teratoma. The cause is unknown, but has been suggested that a teratogenic event occurs as developmental specification reaches the level of the future knee. A central role for the mesenchymal precursor, from which chondro-osseous morphology emerges, has also been suggested. Treatment is surgical and prosthesis is needed in order to improve the quality of life of affected children.
This syndrome has characteristics of fibular aplasia and ectrodactyly. Less than 50 familial and sporadic cases have been reported in the literature. Shortening of the femur, a curved tibia, severe foot anomalies and pathologies of the hip, knee and ankle may also be present. The disorder is probably inherited as an autosomal dominant trait, with reduced penetrance, especially in females.
An extremely rare clinically heterogenous disorder described in about 5 patients to date. Clinical signs included hypotonia, lactic acidosis, and hepatic insufficiency, with progressive encephalomyopathy or hypertrophic cardiomyopathy.
A type of thrombocytosis, a sustained elevation of platelet numbers, which affects the platelet/megakaryocyte lineage and may create a tendency for thrombosis and haemorrhage but does not cause myeloproliferation. The disease usually presents at birth but can be discovered at any time during life and thus can affect all ages. Familial thrombocytosis is caused by germline mutations in the THPO gene (3q26.3-q27) or in the MPL (MPL S505N) gene (1p34).
A lysosomal storage disease belonging to the group of sphingolipidoses. It is very rare with less than 10 cases reported in the literature so far. Clinically, it is a severe neurovisceral disease manifesting immediately after birth and following a rapidly progressive fatal course. The neurological signs and symptoms include hypotonia, massive myoclonic bursts, abnormal ocular movements and dystonia. Grand mal seizures and seizures triggered by tactile stimuli have been described. Patients also develop hepatosplenomegaly. Death usually occurs from respiratory failure following repeated pulmonary infections. The disease is caused by mutations in the PSAP gene (10q21) leading to absence or non-functionality of the prosaposin protein. The mode of inheritance is autosomal recessive.
A form of Ehlers-Danlos syndrome (EDS), with characteristic of spontaneous dissection of medium-sized arteries during young adulthood including mainly the iliac, femoral and renal arteries.
A form of Ehlers-Danlos syndrome (EDS) with characteristics of distinct craniofacial features, multiple contractures, progressive joint and skin laxity, adducted thumb, talipes equinovarus, haemorrhagic diathesis and multisystem fragility-related manifestations.
A form of Ehlers-Danlos syndrome (EDS) with characteristics of severe kyphoscoliosis in conjunction with sensorineural hearing impairment and normal urinary pyridinoline excretion.
A newly described variant of Ehlers-Danlos syndrome (EDS). Affected patients exhibit features consistent with EDS, including joint hypermobility, skin fragility and aortic dilatation. They also have periventricular heterotopia, which has characteristics of focal epilepsy usually beginning in the second decade of life. Intelligence is generally normal. Some patients also have cardiac anomalies such as patent ductus arteriosus, bicuspid aortic valves, or aneurysmal dilatation of the sinus of Valsalva. Caused by mutations in the filamin A gene (FLNA) located at locus Xq28 on the long arm of chromosome X. This suggests a novel cause of EDS. The disease is transmitted as an X-linked dominant trait.
A phenotypic variant of a group of inherited small vessel disorders known as retinal vasculopathy and cerebral leucodystrophy characterised by strokes, vision loss, migraines, pseudotumours, dementia and occasionally renal disease.
A rare form of combined immunodeficiency with characteristics of microcephaly, growth retardation and T and B cell lymphopenia. Patients present in childhood with growth retardation, microcephaly, urogenital and bone malformations, dysmorphic features, including ''bird-like'' facial dysmorphism, and features of combined immunodeficiency. Some patients may also present with autoimmune cytopenia. This disease is caused by mutations in the NHEJ1 (or Cernunos) gene (2q35). The resulting defect of Cernunnos/XLF, a core protein of the non-homologous end-joining (NHEJ) pathway, affects the major mechanism of DNA double-strand break repair. Transmission is autosomal recessive.
A rare syndrome with the association of congenital hypertrichosis in the anterior cervical region, peripheral sensory and motor neuropathy. It has been described in three members of the same family and in one unrelated boy. Associated features in the familial cases include retinal anomalies, spina bifida, kyphoscoliosis and hallux valgus, while that in the non-familial case includes developmental delay. An autosomal recessive mode of inheritance is suggested. There have been no further descriptions in the literature since 1993.
A rare inflammatory bowel disease with characteristics of early cutaneous photosensitivity manifesting by sun-induced facial erythematous and vesicular lesions and severe recurrent colitis that leads to untreatable diarrhea. There have been no further descriptions in the literature since 1991.
A form of syndromic craniosynostosis with characteristics of craniosynostosis, mild facial dysmorphism (prominent supraorbital ridges, mild proptosis and maxillary hypoplasia) and calcification of the basal ganglia. The disease is associated with a favorable neurological outcome, normal intelligence and is inherited in an autosomal recessive manner.
This syndrome has a variable clinical picture of premature coronal suture synostosis with a mild midfacial hypoplasia and hypertelorism, downslanting external palpebral fissures, beaking of the nose and brachydactyly (involving only fingers, not metacarpals). It has been reported in only one family with five affected individuals in three generations. Prenatal diagnosis of abnormal head shape was done at a routine ultrasound examination for one of the grandchildren, at 28 weeks of pregnancy. The pedigree suggests an autosomal dominantly inherited condition, but no gene could be identified for this syndrome, considered as a distinct craniosynostosis entity.
A poly-malformation syndrome with characteristics of craniosynostosis, Poland anomaly, cranio-fronto-nasal dysplasia and genital and breast anomalies. Less than ten cases have been described so far.
3MC syndrome is a disorder characterized by unusual facial features and problems affecting other tissues and organs.The distinctive facial features of people with 3MC syndrome include widely spaced eyes (hypertelorism), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), highly arched eyebrows, and an opening in the upper lip (cleft lip) with an opening in the roof of the mouth (cleft palate).Other common features of 3MC syndrome include developmental delay, intellectual disability, hearing loss, and slow growth after birth resulting in short stature. Less often, individuals with 3MC syndrome can have abnormal fusion of certain bones in the skull (craniosynostosis) or forearm (radioulnar synostosis); an outgrowth of the tailbone (caudal appendage); a soft out-pouching around the belly-button (an umbilical hernia); and abnormalities of the kidneys, bladder, or genitals.3MC syndrome encompasses four disorders that were formerly considered to be separate: Mingarelli, Malpeuch, Michels, and Carnevale syndromes. Researchers now generally consider these disorders to be part of the same condition, which is called 3MC based on the initials of the older condition names.
A rare cranial malformation syndrome with characteristics of premature closure of both lambdoid sutures and the posterior sagittal suture resulting in abnormal skull contour and dysmorphic facial features. Short stature, developmental delay, epilepsy and oculomotor dyspraxia have also been reported. Associated anomalies include enlargement of the cerebral ventricles, agenesis of the corpus callosum, Arnold-Chiari malformation type I, venous anomalies of skull and hydrocephalus.
This syndrome has characteristics of craniofacial dysplasia, cone-shaped physes of the hands and feet and neurological manifestations resembling cerebral palsy. It has been described in one family. The syndrome appeared to be transmitted as a dominant trait.
A well-defined entity within the group of auto inflammatory disorders, it is a rare disease with 49 cases documented so far. It affects mainly young adults and is characterised by recurrent attacks of fever and deep abscess-like collections, most frequently localised in the abdomen. Aseptic abscesses may be either isolated or associated with an underlying condition such as relapsing polychondritis or inflammatory bowel disease. Antibiotics fail to cure the patients but dramatic improvements are seen with corticosteroids and immunosuppressive drugs.
A multiple malformation syndrome with characteristics of atresia of the auditory canal together with ventricular septal defect, anteriorly displaced anus, mild clubfoot and intellectual deficit. It has been described only once, in two sisters.
A card carried in order to alert others in an emergency situation that the card holder has diabetes.
A rare syndrome with characteristics of facial dysmorphism, intellectual deficit and costovertebral abnormalities. To date, 13 cases have been reported in the literature. Dysmorphic features include brachycephaly, hypertelorism, broad nasal bridge, large philtrum, triangular-shaped mouth and micrognathia. There is often synophrys and a low hairline on the back. Costovertebral abnormalities are always present: short, bifid or fused ribs, bony bridges joining the posterior arches in some ribs, hemi vertebrae. Intellectual deficit is constant but the severity varies and patients also have cerebral abnormalities: cortical atrophy, hypoplasia of the corpus callosum and cerebellar vermis.
A rare autosomal dominant neurological disorder with characteristics of early onset cerebellar ataxia, associated with areflexia, progressive optic atrophy, sensorineural deafness, a pes cavus deformity and abnormal eye movements.
Central bilateral macrogyria (rolandic and perisylvian) is a neuronal migration disorder with characteristics of pseudobulbar palsy, developmental delay, mild mental retardation and epilepsy. It has been described in at least four children.
The association of hypertrophic cardiomyopathy with variable malformations of the urogenital tract. To date, it has been described in two brothers born to nonconsanguineous parents. One of the brothers also had dysgenesis of the corpus callosum. The mode of transmission is unknown but may be X-linked or autosomal recessive.
This syndrome has characteristics of non-compaction of the ventricular myocardium, bradycardia, pulmonary valve stenosis and secundum atrial septal defect. Laterality sequence anomalies are also present. So far, the syndrome has been described in nine members from three generations of the same family. Transmission is autosomal dominant and linkage to chromosome 6p24.3-21.2 was reported.
Cap polyposis (CP) is characterised by multiple inflammatory polyps that predominantly affect the rectosigmoid area and manifest primarily as rectal bleeding with abnormal transit, constipation or diarrhoea. To date, around 67 cases have been described in the world literature. The aetiology of CP is still unclear but some causes such as lower colonic mucosal prolapse, mucosal ischaemia, inflammation, abnormal colonic motility, repeated trauma to the colonic mucosa caused by straining, infection and immune disorders have been proposed. CP is not a premalignant condition.
This syndrome has characteristics of camptodactyly, tall stature, scoliosis, and hearing loss (CATSHL). It has been described in around 30 individuals from seven generations of the same family. The syndrome is caused by a missense mutation in the FGFR3 gene, leading to a partial loss of function of the encoded protein, which is a negative regulator of bone growth.
Respiratory failure causing high level of carbon dioxide in the blood.
A rare malformation syndrome with multiple congenital abnormalities, described in 2 siblings, with characteristics of VATER-like association in combination with pulmonary hypertension, laryngeal webs, blue sclerae, abnormal ears, persistent growth deficiency and normal intellect.
A developmental anomaly with characteristics of brachytelephalangy, distinct craniofacial features (prominent square forehead, telecanthus, small nose, malar hypoplasia, smooth philtrum and thin upper lip), and relative to other family members, a short stature. These features may be associated with anosmia and hypogonadotropic hypogonadism (considered as Kallman syndrome). This anomaly has been described in a mother and her son and there have been no further descriptions in the literature since 1986.
A recently described syndrome associating a brachydactyly type A4 (short middle phalanges of the second and fifth fingers and absence of middle phalanges of the second to fifth toes) and a syndactyly of the second and third toes. Metacarpals and metatarsals anomalies are common. This syndrome has been described in two families. It is caused by HOXD13 mutations in 2q31-q32. Inherited as an autosomal dominant trait.
A form of brachydactyly that presents with the characteristic features of brachydactyly type A2 (shortening of the middle phalanges of the index finger and, sometimes, of the little finger) and type D (shortening of the distal phalanx of the thumb) plus various additional features. It has been reported in one family.
A type of brachydactyly characterized by absent middle phalanges of digits 2 to 5.
A form of generalised enchondromatosis with involvement of the spine (so called spondyloenchondromatosis). Spondyloenchondromatosis is a very rare skeletal dysplasia characterised by severe platyspondyly, and mild involvement of hands and feet. It is though to be inherited as an autosomal recessive condition. Dominant pattern of inheritance has been recently suggested.
Limb-girdle muscular dystrophy type 2K has characteristics of onset of muscle wasting during childhood, associated with intellectual deficit. Moderate muscular hypertrophy and microcephaly are also present. So far, the syndrome has been described in ten boys, the majority of whom came from consanguineous Turkish families. The disease is caused by mutations in the POMT1 gene (chromosome 9) encoding O-mannosyltransferase 1, an enzyme involved in protein glycosylation.
A mild form of limb-girdle muscular dystrophy with characteristics of muscle weakness in the four limbs, mild scapular winging, severe atrophy of the quadriceps and anterior tibialis muscles, calf hypertrophy and lack of respiratory and cardiac involvement.
This syndrome has characteristics of congenital thrombocytopenia associated with the presence of large platelets. To date less than 10 cases are reported. The syndrome is caused by mutations in the integrin, beta 3 ITGB3, tubulin, beta-1TUBB1 and actinin, alpha1 ACTN1 genes. These mutations lead to abnormal proplatelets and thrombocytopenia. Transmission is autosomal dominant.
A very rare and atypical form of Chédiak-Higashi syndrome, a genetic disorder with characteristics of partial oculocutaneous albinism, severe immunodeficiency, mild bleeding, neurological dysfunction and lymphoproliferative disorder. Missense mutations in the LYST lysosomal gene (1q42.1-q42.2) appear to cause this form of Chédiak-Higashi syndrome. Inherited in an autosomal recessive manner.
This syndrome has characteristics of progressive ataxia beginning during childhood, deafness and intellectual deficit. It has been described in two families. The clinical picture is similar to that seen in Richards-Rundle syndrome.
A rare association syndrome, reported in several members of two families to date with characteristics of arterial dissection, occurring at an early age and presenting with a range of manifestations depending on the vascular territory involved, in association with cystic medial necrosis and multiple lentigines.
Syndrome with characteristics of moderate to profound hearing loss in both ears and severe nearsightedness (high myopia). The hearing loss may be described as sensorineural or it may be caused by auditory neuropathy. The hearing loss is either present at birth or begins in infancy, before the child learns to speak. This syndrome is caused by mutations in the SLITRK6 gene. The protein produced from this gene is found primarily in the inner ear and the eye. SLITRK6 gene mutations result in an abnormally short SLITRK6 protein that is not anchored properly to the cell membrane meaning the protein is unable to function normally. Impaired SLITRK6 protein function leads to abnormal nerve development in the inner ear and improperly controlled eyeball growth.
This syndrome has characteristics of moderate intellectual deficit, brachycephaly, typical facies (thin lips and microstomia), ectomorphic habitus with extremely long, thin fingers and toes and hypoplastic external genitalia. It has been described in three patients.
An extremely rare association syndrome, described in only two brothers to date (one of which died at 2 months of age), characterised by aplasia cutis congenita of the vertex and generalised oedema (as well as hypoproteinaemia and lymphopenia) due to intestinal lymphangiectasia. There have been no further descriptions in the literature since 1985.
This syndrome has characteristics of the association of aplasia cutis congenita with high myopia, congenital nystagmus and cone-rod dysfunction. It has been described in two siblings (brother and sister). Transmission is autosomal dominant.
An extremely rare malformation syndrome with characteristics of the association of partial distal aphalangia with syndactyly, duplication of metatarsal IV, microcephaly, and mild intellectual disability.
A multiple congenital anomalies syndrome reported in the offsprings of a consanguineous couple with characteristics of multiple congenital skeletal, muscular, ocular and cardiac abnormalities. An autosomal recessive inheritance with variable expressivity was suspected. There have been no further descriptions in the literature since 1992.
The association of ankylosing vertebral hyperostosis with hyperkeratosis of the soles and palms. It has been described in at least eight patients, in four sibships spanning two generations of a Greek-Cypriot family. Six other members of the family presented with palmoplantar hyperkeratosis alone. This syndrome is likely to be transmitted as an autosomal dominant trait. It is distinct from diffuse idiopathic skeletal hyperostosis (DISH), which is not a rare disease.
A rare variant of cutaneous lichen planus with characteristics of both annular and atrophic lichen planus features in the same lesion. Fewer than ten cases have been reported in the literature. Small violaceous papules develop on the trunk and extremities with an atrophic centre and a raised hyperpigmented border. Patients are generally middle-aged and have no past history of cutaneous lesions. Histopathologically, the peripheral border has the typical features of lichen planus, while the centre of the lesion shows loss of rete ridges. There is loss of elastic fibres within the papillary dermis, both centrally and peripherally.
An extremely rare autosomal dominant developmental defect of the eye described in several members of one family with characteristics of the association of moderate intellectual disability with aniridia, lens dislocation, optic nerve hypoplasia and cataracts. There have been no further descriptions in the literature since 1974.
A syndrome described in three members of a family (a boy, his father and his paternal grandmother) with the association of aniridia and patella aplasia or hypoplasia. The grandmother also had bilateral cataracts and glaucoma. There have been no further descriptions in the literature since 1975.
A very rare non-syndromic autosomal recessive pyridoxine-refractory sideroblastic anaemia due to a splice defect of glutaredoxin-5 (GLRX5) described in a single patient with adult onset microcytic hypochromic anaemia with liver iron overload and type 2 diabetes.
A type of arthrogryposis with characteristics of congenital cleft palate, microcephaly, craniostenosis and arthrogryposis. Additional features include facial dysmorphism. Velopharyngeal insufficiency with difficulties in swallowing, increased secretion of the nose and throat, prominent occiput, generalised muscular hypotonia with mild cyanosis and no spontaneous movements, seizures, torticollis, areflexia, intellectual disability, hypertrichosis of the lower extremities, and scleroedema are also observed. The disease often leads to early death. Transmission is autosomal recessive. No new cases have been described since 1983.
A very rare mitochondrial respiratory chain deficiency described in fewer than 10 infants, primarily of middle Eastern descent, with clinical characteristics of transient but life-threatening liver failure with elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinaemia, and lactic acidaemia.
The acute onset of bilateral iris depigmentation, pigment dispersion in the anterior chamber and heavy pigment deposition in the anterior chamber angle of the eye. Patients typically present with acute and usually severe photophobia, blurred vision, red eye and ocular discomfort or pain with a usually self-limiting clinical course. Cases often occur after a flu-like illness, upper respiratory tract infection, and after the use of oral moxifloxacin.
Reported as a new type of acrofacial dysostosis due to the presence of manifestations not usually seen in Nager syndrome such as microcephaly, blepharophimosis, microtia, a peculiar beaked nose, cleft lip and palate, symmetrical involvement of the thumbs and great toes and developmental delay.
A very rare association of a Poland anomaly with characteristics of unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal head) and a variable degree of ipsilateral hand anomalies (including symbrachydactyly, brachydactyly, absent thumb and hypoplastic fingers), combined with a genito-urinary anomaly. Associated genito-urinary anomalies reported include renal hypoplasia or agenesis, duplex collecting system, ureteropelvic junction obstruction, hypospadias and undescended testicles.
A rare developmental defect with characteristics of an anomalous connection of trachea with left hepatic duct presenting with respiratory distress, recurrent respiratory infections and biliary expectoration or vomitus.
The patient's mother is a victim of domestic violence.
A malformation disorder with characteristics of sagittal craniosynostosis, Dandy-Walker malformation, hydrocephalus, craniofacial dysmorphism (including dolichocephaly, hypertelorism, micrognathia, positional ear deformity) and variable developmental delay. The inheritance pattern appears to be autosomal dominant.
Renal papillary necrosis in a patient with a long history of regular analgesic drug use.
Circulatory collapse of obscure cause which occurs in surgical patients who are thought to have a normal blood volume but in whom adequate circulation cannot be maintained.
Syndrome with characteristics of congenital microphthalmia and blindness, progressive spasticity, microcephaly, seizures and profound intellectual deficit. It has been reported in three children from three unrelated families. While imaging at birth is normal, follow-up studies show progressive atrophy involving the cerebral white matter and cortex, cerebellum, brainstem, and corpus callosum. The white matter changes extend into the subcortical region, leaving only small islands of remaining cortical tissue.
An abnormal dark-yellow color of the urine.
A mild form of limb girdle muscular dystrophy that has characteristics of limb-girdle weakness, marked proximal amyotrophy and abolished myotatic reflexes, associated with progressive fingers and toes flexion limitation.
A form of limb girdle muscular dystrophy with characteristics of muscle weakness affecting the pelvic girdle and especially the iliopsoas muscle. Respiratory impairment may be observed in advanced stages.
A limb-girdle muscular dystrophy with characteristics of skeletal and cardiac myopathy with cardiac conduction defects and muscle cytoplasmic inclusions.
A limb girdle muscular dystrophy with characteristics of muscular weakness, primarily affecting the pelvic and shoulder girdles with no bulbar weakness or dysarthria.
A limb girdle muscular dystrophy caused by caveolin-3 deficiency with characteristics of weakness in limb-girdle muscles, calf muscle hypertrophy and lack of respiratory and cardiac involvement.
A limb girdle muscular dystrophy caused by myotilin deficiency with characteristics of limb-girdle weakness in combination with dysarthria.
This syndrome is characterised by the association of intractable diarrhoea of infancy with choanal atresia. Short stature, a prominent and broad nasal bridge, micrognathia, single palmar creases, chronic corneal inflammation, cytopenia, and abnormal hair texture were also reported. So far, the syndrome has been described in three children from the same family. The absence of intellectual deficit and immune deficiency allow this syndrome to be distinguished from other forms of intractable diarrhoea of infancy described previously.
This syndrome is characterised by sleep apnoea associated with glaucoma. It has been described in five members of a family (the mother and four of her children).
This syndrome has characteristics of congenital absence of the teeth and sparse or absent hair. Taurodontia is also present in the majority of cases. The syndrome has been described in less than 15 patients from different families.
A rare syndromic inherited form of sideroblastic anaemia characterised by mild to moderate anaemia (with hypochromia and microcytosis) and early-onset, non or slowly progressive spinocerebellar ataxia. Caused by mutations in the ABCB7 gene (Xq13.3), encoding a mitochondrial ATP-binding cassette (ABC) transporter protein, which plays a role in heme production and iron homeostasis. A mutation in this gene alters the availability of reduced iron and therefore disrupts heme biosynthesis. The ABCB7 gene is highly expressed in both the bone marrow and the cerebellum, which may explain ataxia. Inherited in an X-linked recessive manner.
The association of amelogenesis imperfecta and a microscopically typical hair dysplasia has been found in several members of a family in two generations. Transmission is X-linked.
Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq). Clinical manifestations vary widely depending on the gender of the patient and on the gene content of the duplicated segment. The most frequently reported distal duplications involve the Xq28 segment and yield a phenotype including distinctive facial features, major axial hypotonia, severe developmental delay, severe feeding difficulties, abnormal genitalia and susceptibility to infections. Xq duplications may be caused either by an intrachromosomal duplication or by an unbalanced X/Y or X/autosome translocation.
Timothy syndrome is a multi-system disorder with characteristics of cardiac, hand, facial and neurodevelopmental features that include QT prolongation, webbed fingers and toes, flattened nasal bridge, low-set ears, small upper jaw, thin upper lip, and characteristic features of autism or autistic spectrum disorders. Timothy syndrome is caused by mutations in the CACNA1C gene. It is inherited as autosomal dominant trait. Researchers have identified two forms of Timothy syndrome. Type 1, which is also known as the classic type, includes all of the characteristic features described above. Type 2, or the atypical type, causes a more severe form of long QT syndrome and a greater risk of arrhythmia and sudden death. Unlike the classic type, the atypical type does not appear to cause webbing of the fingers or toes.
This syndrome is characterised by congenital intestinal atresia, umbilical cord ulceration and severe intrauterine haemorrhage. Around 15 cases have been described so far. The aetiology is unknown.
A very rare malformation syndrome with characteristics of hypoplasia of ulna associated with hypoplastic to absent fourth and/or fifth digits, hypoplasia of fibula, short stature and facial dysmorphism.
A very rare syndrome with characteristics of mesomelic shortness of the forearms, bilateral clubfeet, aplasia or hypoplasia of all nails and severe psychomotor retardation. It has been reported in two siblings. The family is suggestive of autosomal recessive inheritance. Prognosis is poor.
This syndrome is characterised by hypokalaemic metabolic alkalosis secondary to a tubulopathy, hypomagnesaemia with hypermagnesuria, severe hypercalciuria and dilated cardiomyopathy. It has been described in two patients, a father and his daughter. The condition shows some similarities to the Gitelman and Bartter syndromes. The mode of transmission appears to be autosomal dominant.
This syndrome has characteristics of axonal sensory and autonomic neuropathy with hearing loss. It has been described in a large five-generation Chinese family. Onset occurred in the second decade of life with mild to severe hearing impairment due to degeneration of the auditory nerve, followed by late-onset of a diffuse and progressive peripheral sensory neuropathy. The causative gene was mapped to the AUNX1 locus on chromosome Xq23-27.3. Transmission was X-linked recessive.
A rare genetic bone disorder with characteristics of chondrodysplasia, intrauterine growth retardation, hydrocephaly and facial dysmorphism in the affected males. The disease is severe and probably lethal in males, the clinical picture in females is less severe. The disease is due to a mutation in the histone deacetylase 6 HDAC6 gene (Xp11.3-q13.1) that causes a nucleotide substitution in the 3' untranslated region (UTR) of the HDAC6 transcript. This mutation lies in the seed sequence of microRNA-433 (hsa-miR-433) and abolishes the post-transcriptional regulation of HDAC6 expression by hsa-miR-433, resulting in the overexpression of the HDAC6 protein. Inheritance is X-linked dominant.
This syndrome has characteristics of facial dysmorphology, neuropathic visceral dysmotility, neurogenic megacystis, intracerebral calcifications and developmental delay. It has been described in two siblings (brother and sister) born to consanguineous parents. The girl also had microcephaly and multicystic kidneys. The boy had a more extensive neuropathic visceral disorder, leading clinically to chronic intestinal pseudo-obstruction syndrome.
This syndrome has characteristics of intellectual deficit affecting both sexes, macrocephaly, and macroorchidism in the majority of affected males. It has been described in 12 individuals from two generations of one family. Other males from this family did not display intellectual deficit but did present macroorchidism and macrocephaly. Transmission is X-linked and the causative gene has been located to the q12-q21 region of the X chromosome.
This syndrome is characterised by severe intellectual deficit, acromegaly and hyperactivity. The syndrome has been described in two half-brothers. Dysarthria, aggressive behaviour, a characteristic facies (an acromegalic and triangular face with a long nose) and macroorchidism were also present. The mother displayed moderate intellectual deficit and milder facial anomalies. Central nervous system anomalies were identified in the two boys: subarachnoid cysts and hyperdensity in the pontine region.
This syndrome has characteristics of cardiac arrhythmias (ventricular extrasystoles manifesting as bigeminy or multifocal tachycardia with syncopal episodes), perodactyly (hypoplasia and/or agenesis of the distal phalanges of the toes) and Pierre-Robin sequence. It has initially been reported in six patients from three generations of one family. Four affected members of another family manifesting a similar constellation of clinical features have recently been reported. An additional feature may be an antimongoloid slant of the palpebral fissures.
Syndrome complex that has characteristics of the cutaneous features of xeroderma pigmentosum together with the systemic and neurological features of Cockayne syndrome. Less than 30 cases have been described to date. The disease manifests during infancy. Patients present with cutaneous UV-sensitive lesions that generally develop into skin cancer and also develop characteristic Cockayne syndrome manifestations such as microcephaly, hydrocephalus, cachexia, premature ageing, dwarfism, skin atrophy, arteriosclerosis, progressive hearing loss, cognitive deficit, spasticity, ataxia, pigmentary retinopathy and optic atrophy. Affected individuals have mutations in one of three XP genes: ERCC3 (2q21), ERCC2 (19q13.3), or ERCC5 (13q22-q34). Transmission is autosomal recessive.
Describes a rare group of immunodeficiencies due to specific mutations in the inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma (IKBKG) or the cytochrome b-245, beta polypeptide (CYBB) genes. The clinical manifestation is mycobacterial infections occurring in males. Diagnosis is made by laboratory analysis. Low levels of IFN-gamma and IL-12 production by the patients' mononuclear cells upon phytohemagglutinin (PHA) are detected in those with an IKBKG mutation. In addition, an impaired IL-12 production by monocytes upon PHA stimulation by activated T cells is shown. Impaired NADPH activity is demonstrated in vitro in macrophages and B-cell lines in those with a CYBB mutation. A mutational analysis is necessary to identify the exact causative genes involved allowing for the implementation of a specific treatment plan.
This syndrome has characteristics of moderate intellectual deficit and precocious puberty. It has been described in three males from two generations of one Australian family. Morbid obesity was noted in the mothers of the patients. Transmission is X-linke
Drugs for dementia can be initiated by a specialist but continued to be prescribed by a general practitioner/primary care physician under a shared care prescribing arrangement.
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A skeletal dysplasia with characteristics of epiphyseal dysplasia (usually mild) associated with progressive myopia, retinal thinning, crenated cataracts, conductive deafness and stubby digits. It has been described in one family in which the mother and three of her four children were affected. The condition is caused by a mutation in the COL2A1 gene (12q13.11-q13.2) and is transmitted in an autosomal dominant manner.
A skeletal dysplasia with characteristics of multiple epiphyseal dysplasia, macrocephaly and facial dysmorphism. It has been described in 4 children from one Omani family. Dysmorphic features consist of macrocephaly with frontal bossing, hypertelorism, flat malar region, low-set ears and short neck. The disease gene has been mapped to the telomeric region of the long arm of chromosome 15. The condition is transmitted in an autosomal recessive manner.
A very rare syndrome with the association of gingival fibromatosis and craniofacial dysmorphism. It has been described in two siblings. Craniofacial dysmorphism consists of relative macrocephaly, bushy eyebrows with synophrys, hypertelorism, downslanting palpebral fissures, flattened nasal bridge and high arched palate. The patients have normal intellect.The condition seems to be hereditary, transmitted as an autosomal recessive trait.
A rare chromosomal disorder in which the tip of the short arm (p arm) of chromosome 10 is deleted resulting in a variable phenotype depending on the size of the deletion. The deletion may involve only the terminal 10p15 band, or extend towards the centromere to bands 10p14 or 10p13. Around 50 cases of pure distal monosomy 10p have been reported. The phenotype remains unclear: low birth weight, persistent growth delay, mild psychomotor retardation and hypotonia have been reported, together with single reports of ventricular septal defect, hydrocephalus and hypogenitalia. Distal monosomy 10p generally occurs de novo or may be associated with a parental translocation.
An exceedingly rare autosomal recessive immune disease with characteristics of thumb aplasia, short stature with skeletal abnormalities and combined immunodeficiency described in three sibships from two possibly related families. The skeletal abnormalities included unfused olecranon and the immunodeficiency manifested with severe chickenpox and chronic candidiasis. No new cases have been reported since 1978.
Syndrome associated with unusual and characteristic multi-organ clinical features, which include hearing loss, congenital heart defects, intellectual disability, hypotonia in infancy and Duane anomaly. It has been described in two patients. The lack of recurrent breakpoints in these two cases and the absence of any low-copy repeats pairs that flank these de novo events do not support non-allelic homologous recombination as the mutation mechanism. The 8q12 region includes CHD7 and it is proposed that this gene, associated with CHARGE syndrome by haploinsufficiency, causes a different phenotype by gain-of-dosage.
A contiguous gene syndrome with characteristics of the association of congenital spherocytosis, dysmorphic features, growth delay and hypogonadotropic hypogonadism. It has been described in 8 patients to date. Common dysmorphic features include micrognathia, microcephaly, preauricular pits, high-arched palate and abnormal ears. All patients except one have intellectual deficit. The syndrome is caused by deletions of the proximal part of the short arm of chromosome 8 (8p11.1 to 8p21). The deletions can be cytogenetically detected and their size is variable. The loss of the ankyrin-1 gene (ANK1) results in congenital spherocytosis.
Syndrome marked by a characteristic facial dysmorphism, short neck and psychomotor retardation, generally associated with a range of non-specific malformations. Isolated terminal 6q deletion syndrome is very rare with less than 20 cases being reported in the literature. The most frequent craniofacial anomalies include microcephaly, broad nose with prominent nasal root and bulbous nasal tip, large ears that may be malformed and low-set and a characteristic downturned mouth. The most commonly described neurological features are psychomotor retardation, hypotonia and seizures. Retinal anomalies are also common. The breakpoints are located between chromosome regions 6q25.3 and 6q26, within the fragile site FRA6E.
The newly described syndrome is associated with microcephaly, short stature, developmental delay and delayed bone maturation. It has been reported in two unrelated patients. There is no remarkable facial dysmorphism. The clinical picture is opposite to that of patients with Sotos syndrome. The breakpoints of the duplication in both patients map to the proximal and distal low-copy repeats which flank the Sotos critical region. These findings support a non-allelic homologous recombination as the mechanism of duplication, and a dosage effect of the Sotos gene NSD1 (5q35).
A recently described syndrome with characteristics of developmental delay, facial dysmorphism and hearing loss. It has been diagnosed in 4 patients. All of them presented with microcephaly, developmental delay, dysmorphic features and hearing loss, two of them had agenesis of the corpus callosum. Dysmorphic features include midface hypoplasia, hypertelorism, broad nasal root and posteriorly rotated ears.This syndrome is caused by an interstitial deletion encompassing 6q25.2-q25.3. These de novo deletions have a variable size with the smallest region of overlap of 3.52 Mb.
A newly described syndrome associated with a variable clinical phenotype including developmental delay, facial dysmorphism, short neck and diverse malformations. Eight cases have been reported to date. The most common facial features include eye anomalies: strabismus, deeply set eyes, and epicanthic folds and ear anomalies such as over-folded helices and low-set ears. Reported patients have deletions of variable size. The critical region for the 6p22 deletion phenotype is 2.2 Mb and encompasses 12 genes; their function is still largely unknown.
The newly described syndrome includes severe intellectual deficit with no speech, stereotypic movements and epilepsy. To date, fourteen patients have been reported. Miscellaneous dysmorphic facial features are present in all cases, but some common features are noticed, high and wide forehead, pronounced eyebrows, anteverted nostrils, short and prominent philtrum, down-turned corners of the mouth and small chin. Stereotypic movements and poor eye contact are present in many patients, suggesting the diagnosis of autism spectrum disorder. The size of deletions varies, the minimal common deleted region encompasses only MEF2C, suggesting that haploinsufficiency of MEF2C is responsible for the phenotype.
A newly described syndrome associated with facial dysmorphism, progressive growth restriction, severe intellectual deficit and absent or severely delayed speech. It has been reported in nine unrelated patients. The most common facial feature includes high or broad forehead, hypertelorism and short philtrum. Short hands and feet are frequently observed. The microdeletion critical region encompasses two candidate genes, PRKG2 and RASGEF1B, in which haploinsufficiency could participate to the phenotype.
A recently described syndrome with characteristics of a variable phenotype involving moderate to severe intellectual deficit, significant speech delay, persistent feeding difficulties, growth retardation and dysmorphic features. It has been described in fewer than 25 patients to date. Facial features include downslanting palpebral fissures, low-set ears and prominent nasal bridge. Most patients also have a high-arched palate or cleft palate. Some individuals have an ectodermal dysplasia-like phenotype, with thin, transparent skin and abnormalities of the hair and teeth. The size of the deletions is variable from 35 kb to 10.4 Mb. Haploinsufficiency of SATB2 is responsible for several of the clinical features.
The newly described syndrome includes severe intellectual deficit with pronounced speech delay, behavioral abnormalities including hyperactivity and inappropriate laughter, short stature and seizures. To date, fifteen patients have been reported. Dysmorphic features include microcephaly, wide and open mouth, a tented upper lip, and prominent incisors. The majority of cases present with stereotypic repetitive behavior, disturbed sleep pattern and a broad-based gait. Skeletal abnormalities include generalized brachydactyly with small hands and feet. The size of the deletions is variable the critical region includes a single gene, MBD5.
The 2p21 microdeletion syndrome consists of cystinuria, neonatal seizures, hypotonia, severe growth and developmental delay, facial dysmorphism, and lactic acidaemia. It has been described in seven patients from three families of a small Bedouin clan. Dysmorphic features include frontal bossing, almond-shaped eyes, long eyelashes, depressed nasal bridge, and large, posteriorly rotated ears. Renal lithiasis occurs at an early age in all patients. Reduced activity of the respiratory chain complexes I, III, IV and V was found in patients examined. The syndrome is caused by homozygous deletion of at least four contiguous genes on chromosome 2: SLC3A1, PREPL, PPM1B and C2orf34 (2p21).
A recently described syndrome with characteristics of developmental delay and facial dysmorphism. Dysmorphic features include receding forehead, telecanthus, epicanthic fold, short and down-slanting palpebral fissures, ptosis, broad and high nasal bridge, retrognathia, flat philtrum, small mouth with high, narrow palate and everted lower lip. This syndrome is caused by an interstitial deletion 2p15p16.1 (present in mosaic in one patient). These de novo deletions have a variable size from 570 kb to 5.7 Mb and encompass several genes. Haploinsufficiency of these genes could contribute to the phenotype.
A recently described syndrome with characteristics of Wolff-Parkinson-White syndrome, variable developmental delay and facial dysmorphism. Dysmorphic features include macrocephaly, hypertelorism, down-slanting palpebral fissures and microstomia. This syndrome is caused by an interstitial deletion encompassing 20p12.3. All these deletions except one occurred de novo and have a variable size with the smallest region of overlap including only one gene, BMP2, which is a good candidate gene for explaining the phenotype of Wolff-Parkinson-White syndrome.
A newly described syndrome associated with facial dysmorphism, developmental delay, in particular of expressive speech, seizures and hypotonia. It has been reported in four unrelated patients. The most common facial features include microcephaly, hypertelorism and thin upper lip. An abnormal corpus callosum (agenesis, hypogenesis or slightly reduced thickness) is observed in all affected patients.
The 19q13.11 microdeletion has characteristics of several major features including pre and postnatal growth retardation, slender habitus, severe postnatal feeding difficulties, microcephaly, intellectual deficit with speech disturbance, hypospadias and ectodermal dysplasia presented by scalp aplasia, thin and sparse hair, eyebrows and eyelashes, thin and dry skin and dysplastic nails. To date, the syndrome has been identified in five patients. Haploinsufficiency of one or more genes in the 19q13.11 region could cause this microdeletion syndrome.
An extremely rare chromosomal anomaly with characteristics of severe speech and language delay, intellectual deficiency, autism spectrum disorder. Less than 10 cases have been reported to date. The syndrome is caused by a hemizygous interstitial microdeletion on the short arm of chromosome 1, occurring mostly de novo, that implicates DPYD (dihydropyrimidine dehydrogenase) and MIR137 genes associated with miRNA pathways.
A newly described syndrome characterised by moderate to severe developmental delay, language delay, bilateral sensorineural and/or conductive hearing loss and facial dysmorphism. It has been reported in 6 patients to date. Facial dysmorphism includes brachycephaly, anteverted nares and ear malformations. Cardiac defects and abnormal behaviour characterised by auto and hetero-aggressivity and hyperactivity can be observed. This interstitial microdeletion was identified by comparative genomic hybridisation microarray and its size is variable.
This syndrome has characteristics of neonatal blisters, milia and congenital absence of dermatoglyphics on the hands and feet. It has been reported in two kindreds (one of which contained 13 affected individuals spanning three generations) and in an unrelated individual. Some affected patients also showed bilateral partial flexion contractures of the fingers and toes, and webbing of the toes. The syndrome is inherited as an autosomal dominant trait.
A recently described syndrome with characteristics of developmental delay, microcephaly, short stature, heart defects and limb abnormalities. The syndrome is caused by an interstitial deletion encompassing 17q23.1q23.2. The underlying mechanism is non-allelic homologous recombination. Parental FISH testing in five of the seven cases confirmed a de novo origin. The minimal deletion region of 2.2 Mb encompasses 2 transcription factors, TBX2 and TBX4, which are good candidate genes for explaining the phenotype.
A recently described syndrome associated with variable developmental delay, facial dysmorphism, seizures and autistic spectrum disorder. This syndrome is caused by an interstitial deletion encompassing 16q24.3. They vary in size the common region of overlap is only 90 kb and comprises two candidates genes, ANKRD11 (Ankyrin Repeat Domain 11) and ZNF778 (Zinc Finger 778).
A recently described syndrome associated with variable clinical features including behavioral abnormalities, developmental delay, congenital heart defects and skeletal anomalies. This syndrome is caused by interstitial duplications encompassing 16p13.11. The size of the rearrangements is variable. The underlying mechanism is non-allelic homologous recombination. The microduplications appear de novo or are inherited from mildly affected or completely normal parents, suggesting that the microduplication has incomplete penetrance and variable expressivity. As the duplication is present in phenotypically normal parents of patients, as well as in the general population, the clinical significance of the 16p13.11 microduplication is still unclear.
A recently described syndrome characterised by developmental delay, microcephaly, epilepsy, short stature, facial dysmorphism and behavioural problems. Facial features include down-slanting palpebral fissures, short nose, low-set ears, wide mouth and thin upper lip. Variable congenital anomalies can also be observed. This syndrome is caused by an interstitial deletion encompassing 16p13.11. The underlying mechanism is non-allelic homologous recombination. Microdeletions appear de novo or are inherited from mildly affected or completely normal parents in an autosomal dominant manner, suggesting that the microdeletion has incomplete penetrance and variable expressivity.
A recently described syndrome with characteristics of developmental delay and facial dysmorphism. Facial features include flat facies, downslanting palpebral fissures, low-set and malformed ears. Orofacial clefting, heart defects, short stature, feeding difficulties and hypotonia can be observed. This syndrome is caused by an interstitial deletion encompassing 16p11.2-p12.2. These deletions arise de novo and are flanked by segmental duplications suggesting that the underlying mechanism is non-allelic homologous recombination.
A sighted guide is a person that escorts a visually impaired individual and assists them with for example reading of signs.
This syndrome has characteristics of variable psychomotor delay and dysmorphic features. It has been recently described in less than ten patients. Clinical presentation is variable but it is possible to delineate a common clinical spectrum comprising mild to moderate psychomotor delay, hypotonia and discrete craniofacial dysmorphic features including a high forehead with frontal bossing, a small nose and a small mouth. The microduplication encompasses the same region that is deleted in Miller-Dieker (17p13 deletion) syndrome. The variable size of this de novo duplication indicates that mechanisms other than nonallelic homologous recombination may be responsible.
Syndrome that has characteristics of dysmorphic features and intellectual deficit. It has been described in seven patients within one family. 17q11.2 microduplication encompasses the NF1 region. The underlying mechanism may be non-allelic homologous recombination. The study of pedigree suggests that this microduplication segregates within the family for at least two generations. Two patients displayed a normal clinical presentation, suggesting an autosomal dominant pattern of inheritance with incomplete penetrance.
A progressive autosomal dominant macular dystrophy with characteristics of parafoveal hypopigmentation followed by a retinitis pigmentosa-like phenotype (nyctalopia and peripheral vision loss) with a bull's eye configuration.
This syndrome has characteristics of slowly progressive unilateral exophthalmos and ipsilateral mucosal turbinate hypertrophy, without intraorbital or intranasal lesions. Only four cases have been described so far. Treatment with a corticoid nasal spray led to regression of the exophthalmos within several days.
A rare genetic skin disorder with the absence of scalp and body hair and palmoplantar keratoderma, without other hand complications. To date, ten individuals have been reported. Usually presents during infancy with manifestations of fading of facial, scalp and body hair within the first months of life without subsequent re-growth. Body and facial keratosis pilaris are additional features that appear in the following years. Palmoplantar keratoderma develops during infancy and may have an unusual pattern. The genetic basis is unknown. Transmission appears to be autosomal dominant.
A form of focal dystonia with characteristics of cervical, laryngeal and hand-forearm dystonia.
A mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, with characteristics of distal legs sensory loss and weakness that can be asymmetric. Tendon reflexes are reduced in the knees and absent in ankles. Progression is slow.
A form of axonal Charcot-Marie-Tooth disease, a peripheral motor and sensory neuropathy with characteristics of congenital pstosis and early cataract. Associated with a mildly progressive peripheral neuropathy of variable onset from birth to the sixth decade, pes cavus, reduced to absent ankle tendon reflexes and sometimes neutropenia.
A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy. In the single family reported to date, onset is between 15 and 33 years. Patients present with a symmetric distal weakness of legs and occasionally of the hands, absent or reduced tendon reflexes, distal legs sensory loss and frequently a pes cavus. Progression is slow.
A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy with onset associated with development of foot deformity and walking difficulties between the first and the eighth decades. Weakness and sensory loss involve primarily the legs and ankles, tendon reflexes are reduced. The disease has a slowly progressive course.
A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy with symmetric weakness primarily occurring in the lower limbs and reaching the arms only after 5 to 10 years, occasional and predominantly distal sensory loss and reduced tendon reflexes. Presents with gait anomaly between the first and sixth decade and early onset is generally associated to a more severe phenotype that may include foot drop.
Decline of physiological, mental or physical functional process applied to any age range and any baseline status.
A multiple congenital anomalies syndrome described in a father and son with the association of cleft palate, peculiar facies (asymmetrical appearance, inner epicanthal folds, short nose, anteverted nostrils, low and back-oriented ears, thin upper lip and micrognathism), short stature, short neck , vertebral anomalies and intellectual disability. The transmission is presumed to be autosomal dominant. There have been no further descriptions in the literature since 1993.
Cone dystrophy with supernormal rod response is an inherited retinopathy, with an onset in the first or second decade of life. The disease has characteristics of poor visual acuity (due to central scotoma), photophobia, severe dyschromatopsia and occasionally nystagmus. Night blindness usually develops later in the course of the disease, but it can also be apparent from childhood. A hallmark of the disease is the decreased and delayed dark-adapted response to dim flashes in electroretinographic recordings, which contrasts with the supernormal b-wave response at the highest levels of stimulation.
A severe anomaly of bile acid synthesis with manifestation of severe neonatal cholestatic liver disease. To date, only 2 cases of this disorder have been reported. Caused by mutations in the 7-alpha hydroxylase gene (CYP7B1, 8q21.3). The deficiency in oxysterol 7-alpha-hydroxylation leads to the accumulation of hepatotoxic unsaturated monohydroxy bile acids. The mode of transmission is presumed to be autosomal recessive.
A rare developmental defect with characteristics of an anomalous connection of bronchus with left hepatic duct presenting with respiratory distress, recurrent respiratory infections and biliary expectoration or vomitus.
A subtype of junctional epidermolysis bullosa the condition occurs in childhood or young adulthood. 22 patients in 12 families have been reported to date. Blistering occurs at first around nails, accompanied by nail dystrophy and shedding, and then affects the hands and feet and, to a lesser extent, the elbows, knees, along with atrophic scarring. Other manifestations include disappearance of dermatoglyphs and palmoplantar hyperhidrosis. Extracutaneous involvement is restricted to soft tissue abnormalities of the oral cavity and enamel defects with development of caries. COL17A1 mutations have recently been described in an affected family. The condition follows an autosomal recessive pattern of inheritance.
Leber plus disease describes patients with the clinical features of Leber's hereditary optic neuropathy in combination with other serious systemic or neurological abnormalities. These abnormalities include: postural tremor, motor disorder, multiple sclerosis-like syndrome, spinal cord disease, skeletal changes, Parkinsonism with dystonia, anarthria, dystonia, motor and sensory peripheral neuropathy, spasticity and mild encephalopathy. It is caused by maternally inherited mitochondrial DNA (mtDNA) mutations.
Syndrome characterised by neurobehavioural disorders, hypotonia, cognitive deficit, language delay and seizures. Prevalence is unknown. The clinical picture is highly variable even within the same family. Paternal duplications are rarely symptomatic (developmental delay/ behavioural disorders). The syndrome is due to interstitial duplications that encompass the imprinted Prader-Willi/Angelman critical region, of which deletions lead to Prader-Willi and Angelman syndromes. The causative genes are imprinted and expressed from the maternal allele.
The sudden, unexpected, witnessed or unwitnessed, non-traumatic, and non-drowning death in patients with epilepsy with or without evidence for a seizure, and excluding documented status epilepticus, in which postmortem examination does not reveal a structural or toxicological cause for death.
Syndrome with characteristics of cleft soft palate, severe oligodontia of the deciduous teeth, absence of the permanent dentition, bilateral conductive deafness due to fixation of the footplate of the stapes, short halluces with a wide space between the first and second toes, and fusion of carpal and tarsal bones. It has been described in two sisters of Swedish extraction. An autosomal recessive mode of inheritance is likely. There have been no further descriptions in the literature since 1971.
Larsen-like syndrome, lethal type, has characteristics of multiple joint dislocation and respiratory insufficiency due to tracheomalacia and or lung hypoplasia. It has been described in less than ten patients. Transmission is thought to be autosomal recessive. Brain dysplasia has been described in some patients. Genetic factors have not been ruled out.
The association of leukoencephalopathy and metaphyseal chondrodysplasia has been reported in four men from a three-generation family. Onset manifests by spastic paraplegia at the age of 2, followed by tremor, ataxia, optic atrophy, and spastic tetraparesis. Transmission is X-linked and the gene responsible of the disease may be located at Xq25-q27.
This disease is a non-progressive neurological disorder marked by intellectual deficit, spasticity and motor retardation associated with characteristic MRI findings of anterior bilateral temporal lobe cysts and multilobar leukoencephalopathy. So far, around 30 cases have been reported in the literature. Onset occurs in the first few months of life. Sensorineural deafness and microcephaly have also been reported.
An extremely rare lethal form of chondrodysplasia with characteristics of severe micromelic dwarfism, short and incurved limbs with normal hands and feet, facial dysmorphism (disproportionately large skull, frontal prominence, slightly flattened nasal bridge and short neck), muscular hypotonia, hyperlaxity of the extremities, and a narrow thorax. Most patients die of respiratory distress during the first hours or weeks of life. There have been no further descriptions in the literature since 1988.
Waters-West syndrome is characterised by the association of lethal non-spherocytic, non-immune haemolytic anaemia with abnormalities of the external genitalia (micropenis and hypospadias), flat occiput, dimpled earlobes, deep plantar creases, and increased space between the first and second toes. It has been described only once in two brothers who died a few hours after birth. The second-born infant had massive ascites and hepatosplenomegaly. The mother had two spontaneous abortions but gave birth to a normal girl, suggesting an autosomal or X-linked recessive mode of inheritance.
An extremely rare arthrogryposis syndrome, described in only two pairs of siblings from two unrelated families to date with the association of arthrogryposis, congenital torticollis, dysmorphic facial features (i.e. asymmetry of the face, myopathic facial movements, ptosis, posteriorly rotated ears, cleft palate), progressive scoliosis and episodes of malignant hyperthermia. There have been no further descriptions in the literature since 1988.
This syndrome has characteristics of microcephaly, severe intellectual deficit, phalangeal anomalies (cutaneous syndactyly of the fingers, toe brachyclinodactyly and nail hypoplasia) and neurological manifestations (epilepsy, spastic/dystonic paraplegia and brisk reflexes). Hypotonia, pre and postnatal growth retardation, a characteristic face (broad forehead with a low frontal hair line, a broad nasal bridge and prominent columella, hypoplastic alae nasi, short philtrum, and a straight mouth with thin lips and downward slanting palpebral fissures) and optic atrophy were also reported.
The syndrome is characterised by generalised multiple steatocystoma and natal teeth. It has been described in a five-generation Chinese family with at least 21 affected patients. The same condition has been reported in one additional sporadic case. Autosomal dominant inheritance has been suggested.
This syndrome is characterised by white plaque-like lesions involving the macula but sparing the peripapillary areas of both eyes. It has been described in five patients. In contrast to patients with macular serpiginous choroiditis presenting with similar lesions, the five patients reported so far had good visual acuity until the onset of choroidal neovascularisation or pigmentary mottling. The macular lesions fade after several months or years, but the vascular anomalies persist leading to a loss of central vision.
An X-linked ciliary dysfunction disorder of both the respiratory epithelium and photoreceptors of the retina. This leads to ocular problems including mild night blindness, constriction of the visual field and scotopic and photopic ERG responses reduced to 30-60%. It is also associated with primary ciliary dyskinesia manifestations including chronic bronchorrhea with bronchoectasis and chronic sinusitis along with sensorineural hearing loss.
DYT13 type primary dystonia has characteristics of focal or segmental dystonia with cranial, cervical, or upper limb involvement. It has been reported in individuals from three generations of one large Italian family. Age of onset varied between 5 years and adulthood. The clinical manifestations were generally mild and slowly progressive. The causative gene locus has been identified on chromosome 1p36.13-1p36.32. Transmitted in an autosomal dominant manner.
An extremely rare disorder described in one family to date that has characteristics of progressive, late onset, autosomal dominant sensorineural hearing loss, QT interval prolongation and mild cardiac hypertrophy.
Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with adrenocorticotrophin hormone independent Cushing syndrome. The disease has characteristics of small to normal sized adrenal glands containing multiple small cortical pigmented nodules. A substantial proportion of patients present during early childhood (2-3 years). More than 90% of reported cases of PPNAD occur as one of the manifestations of Carney complex. The condition is inherited in an autosomal dominant manner and can be associated with mutations in the PRKAR1A, PDE11A and PDE8B genes.
Progressive non-infectious anterior vertebral fusion (PAVF) is an early childhood spinal disorder with characteristics of the gradual onset of thoracic and/or lumbar spine ankylosis often in conjunction with kyphosis with distinctive radiological features. Prevalence is unknown, but PAVF (mostly isolated cases) has been reported in approximately 80-100 cases. Neurological abnormalities are exceptional. PAVF can occur isolated or less frequently, as part of a syndrome. Syndrome associated manifestations include facial dysmorphism, absence of one cervical vertebrae, radio-ulnar synostosis, exostosis.
Progressive cavitating leukoencephalopathy has characteristics of acute episodes of neurological deficit (ataxia, dysarthria, seizures) with irritability and opisthotonus followed by either steady deterioration or alternating periods of rapid progression and prolonged periods of stability. So far around 20 patients have been reported in the literature. Onset occurs in infancy or early childhood. The mode of transmission is autosomal recessive.
This syndrome combines short stature, sparse hair, skin hyperpigmentation and urticaria-like reactions on the hands and arms. An upper central incisor, hypoplastic thumbs and/or palmoplantar hyperkeratosis may also be present. It is thought to be a rare form of ectodermal dysplasia and has been described at least once in a mother and her three sons. Transmission is autosomal dominant, or X-linked.
This syndrome has manifestations of the association of spondylometaphyseal dysplasia (marked by platyspondyly, shortening of the tubular bones and progressive metaphyseal irregularity and cupping), with postnatal growth retardation and progressive visual impairment due to cone-rod dystrophy. So far, it has been described in eight individuals. Transmission appears to be autosomal recessive.
Disease with characteristics of short trunk dwarfism, progressive involvement of the spine and epiphyses and mild-to-moderate intellectual deficit.The syndrome has been described in three daughters born to healthy consanguineous parents. The skeletal disorder usually manifests in late childhood. Typical radiographic features include platyspondyly, abnormal lumbar vertebrae and degenerative large joint changes. Autosomal recessive transmission has been suggested.
Hair that can be removed without resistance.
Disease that has characteristics of disproportionate early-onset dwarfism, bowing of the lower limbs, short, wide and stocky long bones with severe epiphyseal and metaphyseal changes, lumbar lordosis, hypoplastic iliac bones, flat ovoid vertebral bodies and normal hands. The syndrome has been described in a large consanguineous Arab Muslim family. It is caused by mutation in the matrilin-3 gene (MATN3, 2p24-p23) and transmitted in an autosomal recessive manner.
Symmetrical thalamic calcifications are clinically distinguished by a low Apgar score, spasticity or marked hypotonia, weak or absent cry, poor feeding and facial diplegia or weakness. It is an extremely rare condition, with about 30 cases described in the literature. The calcifications are revealed by computed tomography scanning. The prognosis is very poor.
This syndrome is characterised by mild to severe intellectual deficit associated with variable clinical manifestations including spasticity, cryptorchidism, maxillary hypoplasia, alopecia areata, epilepsy, short stature, impaired speech and behavioural problems. To date, it has been described in less than 15 families. Transmission is X-linked recessive and the syndrome is caused by mutations in the JARID1C (SMCX) gene encoding a JmjC-domain protein with histone demethylase activity.
This syndrome has characteristics of X-linked intellectual deficit, obesity, hypogonadism, and tapering fingers. It has been described in ten males from a large Pakistani family. The causative gene has been located to Xp11.3-Xq23.
This syndrome has characteristics of intellectual deficit, epilepsy, facial dysmorphism and progressive joint contractures. It has been described in two boys. Hypotonia and feeding problems at birth were also reported. The mode of transmission is X-linked.
This syndrome is characterised by severe intellectual deficit, hypotonia, mild facial dysmorphism and aggressive behaviour. It has been described in 10 male members spanning four generations of one family. The facial dysmorphism includes a high forehead, prominent ears, and a small pointed chin. Height and head circumference are reduced. This disorder is transmitted as an X-linked recessive trait and the causative gene maps to Xp22.
This syndrome is characterised by moderate intellectual deficit, bilateral single palmar creases, seizures, variable hypogammaglobulinaemia and characteristic features (synophrys, prognathism, and hirsutism). It has been reported in three males from two generations of one family. All underwent progressive neurological deterioration.This syndrome is transmitted as an X-linked trait, and the causative gene is located between Xq21.33 and Xq23.
This syndrome has characteristics of intellectual deficit associated with facial dysmorphism, patella luxation and abnormal growth of the teeth. It has been described in eight males from multiple generations of one family. The locus for the causative gene for this syndrome has been located to the region between p11.22 and p21.1 on the X chromosome.
This syndrome has characteristics of moderate intellectual deficit, marked cubitus valgus, mild microcephaly, a short philtrum, deep-set eyes, downslanting palpebral fissures and multiple nevi. Less than ten individuals have been described so far. Transmission is thought to be X-linked recessive.
This syndrome has characteristics of intellectual and motor deficit, spastic quadriparesis and agenesis of the corpus callosum, without craniofacial abnormalities or seizures. It has been described in four male members of a family. The mode of inheritance is most likely X-linked recessive.
A rare syndromic form of cerebellar dysgenesis with characteristics of moderate to severe intellectual deficit and cerebellar abnormalities. OPHN1 syndrome is very rare. To date, up to 12 families have been reported. Affected male patients present moderate to severe intellectual disability, hypotonia, severe developmental delay, early-onset complex partial or tonic-clonic seizures, strabismus, dysmetria and occasionally ataxia. Cryptorchidism and genital hypoplasia have been reported. Various mutations including deletions and splice site mutations in the OPHN1 gene (Xq12) have been reported in patients with this syndrome. Transmission appears to follow an X-linked semi-dominant pattern.
A rare genetic skin disorder with characteristics of congenital alopecia and palmoplantar hyperkeratosis. It is usually associated with cataracts, progressive sclerodactyly and pseudo-ainhum. To date the syndrome has been reported in two families (seven affected individuals) plus an additional sporadic patient was likely affected by the same condition. Usually presents during infancy with manifestations of fading of facial, scalp and body hair within the first months of life without subsequent re-growth. Body and facial keratosis pilaris are additional features that appear in the following years. Skin thickening of palms and soles develops during infancy and may have an unusual pattern affecting the two sides of fingers and palms, but usually sparing the palmar surfaces.
This syndrome has characteristics of progressive spastic paraplegia and distal muscle wasting. So far, it has been described in two families. All affected individuals carried mutations in the neuropathy target esterase (NTE) gene, encoding a neural membrane protein.
This syndrome has characteristics of mild intellectual deficit, congenital cataract, progressive sensorineural deafness and ataxia. It has been described in two sisters. The inheritance is likely to be autosomal recessive.
An X-linked mental retardation syndrome belonging to the group of conditions with manifestations of intellectual deficit with hypotonic facies. Prevalence is unknown but the syndrome was originally described in 1988 in six males from three generations of one family. In the affected males the syndrome has characteristics of coarse facial appearance (prominent lips, bushy eyebrows, widely-spaced teeth, and a broad and depressed nasal bridge with a wide nasal tip), brachydactyly with widening of the distal phalanges, short stature and moderate intellectual deficit. The syndrome is caused by mutations in the ATRX gene (Xq13.3).The syndrome is transmitted as an X-linked recessive trait with skewed X-inactivation in carrier females.
This syndrome has characteristics of neonatal trigonocephaly and multiple anomalies including craniosynostosis, shallow orbits, unusual nose, deviation of the terminal phalanges of fingers and broad toes with duplication of the terminal phalanx. It has been described in a mother and her son. It is transmitted as an autosomal dominant trait.
This syndrome has characteristics of trigonocephaly, brachycephaly, bulbous nose (bifid at the tip), micrognathia, macrostomia, hypotonia and relatively broad metatarsals and phalanges. It has been described in a brother and his sister born to consanguineous parents.
A recently described syndrome with characteristics of developmental delay, hypotonia and facial dysmorphism. It has been clinically and molecularly described in 3 patients. All three children have similar dysmorphic features, including widely-spaced eyes, short nose with flat nasal bridge, long philtrum, prominent Cupid's bow, full lower lip and similar auricular anomalies. This syndrome is caused by an interstitial deletion encompassing 14q11.2.
Orbital leiomyoma is a rare benign smooth muscle tumor arising from the walls of orbital vessels characterized by its slow growth and well encapsulated nature. It is usually located in an extraconal position, commonly manifesting with painless proptosis. The tumor is composed of spindle cells arranged in a fibrous stroma rich in dilated sinusoidal capillaries. The nuclei of tumor cells are oval with blunted ends and there are no mitotic figures.
Partial agenesis of the pancreas is an absence of a critical mass of pancreatic tissue. It is a rare disorder with only around 50 cases being reported in the literature so far. The severity of the disease depends on the amount of functional pancreatic tissue present. Pancreatic agenesis is commonly associated with other malformations, in particular pancreaticobiliary duct anomalies or more rarely, polysplenia. In the majority of cases, patients are diagnosed after reporting abdominal pain. Agenesis of the dorsal pancreas usually manifests as diabetes. Pancreatic agenesis has been associated with mutations in the PDX1 gene (13q12.1), which encodes the insulin promoter factor-1 (IPF-1) transcription factor.
VACTERL is an acronym for Vertebral anomalies, Anal atresia, Congenital cardiac disease, Tracheoesophageal fistula, Renal anomalies, and Limb defects. VACTERL associated with hydrocephalus has rarely been reported and is thought to be an autosomal recessive anomaly. The condition is described as a uniformly lethal or developmentally devastating disorder distinct from the VATER association.
This syndrome is characterised by coloboma of the iris, bilateral cleft lip and palate and intellectual deficiency of varying degree. A wide variability in clinical expression is observed. Some patients also present with microphthalmia, cataract, glaucoma, ptosis, sensorineural hearing loss and haematuria. To date, 12 cases have been described from three generations of a single family. Transmission is autosomal dominant.
This syndrome has characteristics of X-linked intellectual deficit and mild variable manifestations, including short stature, small head circumference, sloping forehead, hearing loss, abnormally shaped ears, and small testes. It has been described in eight affected males from three generations.
This syndrome has characteristics of intellectual deficiency, short stature, seizures and small hands and feet. It has been described in six males from three generations of one family. Three of them also had cataracts and or glaucoma and two of them had cleft palate. The locus has been mapped to the terminal 8 Mb of Xq28.
Characterised by marked neonatal hypotonia, progressive quadriparesis, severely delayed developmental milestones (walking at 3 years of age), gastrooesophageal reflux, and stereotypic movements of the hands, esotropia and infantile autism. It has been described in two related males, whereas female carriers were unaffected. Pericentric inversion inv(X)(q13;p22) has been identified it results in the absence of the product of the KIAA2022 gene, highly expressed in the brain.
X-linked intellectual deficit Cilliers type has characteristics of mild intellectual deficit associated with short stature, hypergonadotropic hypogonadism, microcephaly and mild facial dysmorphism (deep-set eyes, prominent supraorbital ridges, a high nasal bridge and large ears). It has been described in four males from one family. The syndrome is mapped to the Xq25-q26 region of the X-chromosome. The syndrome is transmitted in an X-linked recessive manner.
X-linked mental retardation Miles-Carpenter type has characteristics of severe intellectual deficit, microcephaly, exotropia and low digital arches. It has been described in four male members of one family. Joint hypermobility, distal muscle wasting, hypogonadism and rocker bottom feet were also reported. Low digital arches and exotropia were described in several female members of the family. Transmission is X-linked and the causative gene has been mapped to Xq13-q22.
This syndrome has characteristics of the association of dysmorphism with intellectual deficit. It has been described in four generations of one family. Premature death was reported in the affected males. Transmission is X-linked recessive and the causative gene has been located to the q28 region of the X chromosome.
X-linked mental retardation Schimke type has characteristics of intellectual deficit, growth retardation with short stature, deafness and ophthalmoplegia. Choreoathetosis with muscle spasticity generally appears during childhood. It has been described in four boys, three of whom were from the same family. Transmission is X-linked.
This syndrome has characteristics of severe intellectual deficit with mutism, epilepsy, growth retardation and recurrent infections. It has been described in three males from three generations of one family. The causative gene has been located to the 11p region of the X chromosome.
X-linked intellectual deficit Van Esch type has characteristics of mild to moderate intellectual deficit associated with low birth weight, short stature, microcephaly and variable hypergonadotropic hypogonadism. It has been described in seven males from a family of Belgian origin. The syndrome is transmitted in an X-linked recessive manner and mapped to the Xp22.1-p21.3 region of the X-chromosome.
X-linked mental retardation, Turner type has characteristics of moderate to severe intellectual deficit in boys and moderate intellectual deficit in girls. It has been described in 14 members from four generations of one family. Macrocephaly was reported and holoprosencephaly may also be present (two family members). The mode of transmission is X-linked semi-dominant.
This syndrome has manifestations of intellectual deficit, short stature and characteristic facies (hypertelorism, prominent forehead, frontal bossing, a broad nasal tip and anteverted nares). It has been described in four males from three generations of the same family. Two females from this family also displayed intellectual deficit and the characteristic facies. Transmission is X-linked.
This syndrome is characterised by severe intellectual deficit with hyperactivity, language delay, congenital hip luxation, short stature, kyphosis and recurrent respiratory infections. Aggressive behaviour and frequent epileptic seizures may also be present. The syndrome has been described in four boys from the same family. Transmission is X-linked and is caused by mutations in the KIAA1202 gene, localised to the Xp11.2 region.
This syndrome has characteristics of intellectual deficit, hypotonia, absent deep tendon reflexes, tapered fingers and excessive fingerprint arches, genu valgum, a characteristic face and small teeth. It has been described in four males from two generations of one family. The causative gene appears to be located in the q13 region of the X chromosome.
This syndrome is characterised by mild to borderline intellectual deficit associated with cleft lip/palate. Preaxial polydactyly, large hands and cryptorchidism are sometimes present. The syndrome has been described in seven boys from two families. Transmission is X-linked and the syndrome is caused by mutations in the PHF8 gene, localised to the p11.21 region of the X chromosome.
This syndrome is characterised by the association of severe intellectual deficit with microcephaly, strabismus and short stature. It has been described in three boys from two unrelated families. Transmission is X-linked recessive and the causative gene has been localised to the q12-Xq21.31 region of the X-chromosome.
This syndrome has manifestations of moderate intellectual deficit, obesity, macroorchidism and a characteristic facies (large ears, a prominent lower lip and puffy eyelids). It has been described in nine boys from two families. Transmission is X-linked and the causative gene has been localised to the q21.3-q27 region of the X chromosome.
This syndrome has characteristics of microcephaly, intellectual deficit, growth retardation and hypogenitalism. It has been described in four boys from one family. A characteristic facies and ophthalmologic anomalies were also present and included microphthalmia, microcornea and cataract. Transmission is X-linked.
This syndrome combining intellectual deficit, ciliary dysfunction and macrocephalus has been described in several males from one large family. Ciliary dysfunction leads to recurrent pulmonary infections and death in most cases. This syndrome is a recessive X-liked mental retardation and has been associated with mutations in the OFD1 gene, known to be involved in oral-facial-digital syndrome.
A recently described syndrome with characteristics of short stature, hypogonadism, developmental delay and facial dysmorphism. Facial features include deep-set eyes, bulbous nasal tip and thin lips. Hypogonadism is due to primary gonadal failure. Patients also had some features that are probably caused by testosterone deficiency such as a high-pitched voice, sparse body hair and small hands and feet. Carrier females present with a short stature and early menopause. This syndrome is caused by an Xq27.3q28 interstitial duplication encompassing the FMR1 and AFF2 genes but not the MECP2 gene. Transmission is X-linked.
An extremely rare mitochondrial disorder with characteristics of facial dysmorphism similar to that seen in Zellweger syndrome. These features include frontal bossing, high forehead, up slanting palpebral fissures, hypoplastic supraorbital ridges, and epicanthal folds and in addition, pale skin, profound hypotonia, developmental delay and minor metabolic anomalies. No peroxisomal defects have been reported. Transmission is thought to be autosomal recessive.
This syndrome is characterised by the association of total bilateral congenital cataract with the secondary occurrence of glaucoma appearing at ages varying between 10 and 40 years. This very rare syndrome has only been described in three families, one of which contained a few dozen affected individuals spanning eight generations. The disorder is transmitted as an autosomal dominant trait and is caused by dysfunction of the PITX3 gene (localised to 10q25). This gene codes for a transcription factor involved in the development of the lens and anterior segment of the eye.
Autosomal recessive limb girdle muscular dystrophy type 2E (LGMD2E) is a limb girdle muscular dystrophy with characteristics of limb-girdle weakness, particularly of the pelvic girdle muscles.
This syndrome is characterised by generalised hypotonia, psychomotor deficit, congenital ataxia and recurrent bronchopulmonary infections. It has been described in seven males from three generations of a family. Five of them died during the first years of life and the remaining patients developed myoclonic encephalopathy and macular degeneration. The locus has been mapped to Xp22.33-pter.
A rare X-linked mental retardation syndrome with characteristics of psychomotor delay, intellectual deficit, hydrocephalus, and mild facial anomalies. Prevalence is unknown, but the syndrome was originally described in a large Scottish family. Mutations in the AP1S2 gene (Xp22), coding for a subunit of the clathrin-associated adaptor protein complex involved in intracellular protein trafficking and synaptic vesicle recycling, have been identified in seven families.
This syndrome is an X-linked neurodegenerative disorder with characteristics of intellectual deficit, blindness, convulsions, spasticity, mild hypomyelination and early death. It has been described in about ten male members from two generations of one family. The genetic defect responsible for the disorder is located in the pericentromeric region of the X chromosome, Xp11.3-q12.
This syndrome is characterised by severe intellectual deficit with inability to walk and speak, muscle atrophy, and urinary and faecal incontinence. It has been described in six males of a Brazilian family.
This syndrome has characteristics of ataxia, apraxia, intellectual deficit and or seizures. It has been described in nine males in two unrelated Danish families. It is transmitted as an X-linked recessive syndrome with partial clinical expression in obligate female carriers.
This syndrome has characteristics of mild intellectual deficit, failure to thrive, short stature and osteopoikilosis. It has been described in four unrelated patients. The syndrome appears to be caused by a heterozygous deletion at chromosome region 12q14, which was detected in three of the four patients. The deleted region contains the LEMD3 gene: mutations in this gene have already been implicated in osteopoikilosis.
This syndrome has characteristics of the association of severe congenital colitis with sensorineural deafness. So far, two cases with neonatal onset have been described. Endoscopy reveals a smooth mucosa without ulcerations but histological studies reveal abnormal vacuolated epithelial cells with premature exfoliation within the glandular lumens, accompanied by increased mucus production and an increase in cholinergic fibres within the lamina propria.
Spondyloepiphyseal dysplasia Nishimura type has characteristics of spondyloepiphyseal dysplasia, craniosynostosis, cataracts, cleft palate and intellectual deficit. The syndrome has been described in four Japanese siblings born to nonconsanguineous parents. Most clinical manifestations are evident at birth, but skeletal changes and cataracts may become evident during early childhood.
An extremely rare type of spondyloepiphyseal dysplasia described in several members of a single family to date and with characteristics of short stature, vertebral and femoral abnormalities, cervical instability and neurological manifestations secondary to anomalies of the odontoid process.
Spondyloepiphyseal dysplasia MacDermot type has characteristics of short stature, femoral epiphyseal dysplasia, mild vertebral changes and sensorineural deafness. The syndrome has been described in a family in which females in four successive generations were affected. Myopia and retinal detachment were present in adult life.
The association of a range of ocular anomalies (anophthalmia, microphthalmia and retinal abnormalities) with variable developmental delay and central nervous system malformations. Less than 20 cases have been reported in the literature so far. The clinical picture is highly variable, even between affected members of the same family. Severe developmental delay was noted in some patients, whilst others showed normal cognitive development. Pituitary dysfunction, leading to growth hormone deficiency and short stature, or combined pituitary hormone deficiency, has also been reported. The syndrome is caused by heterozygous mutations in the OTX2 gene (14q22.3).
A congenital cortical development anomaly due to abnormal neuronal migration involving neocortical and hippocampal lamination, corpus callosum, cerebellum and brainstem. A large clinical spectrum can be observed, from children with severe epilepsy and intellectual and motor deficit to cases with severe cerebral dysgenesis in the antenatal period leading to pregnancy termination due to the severity of the prognosis.
A form of familial primary hypomagnesaemia characterised by low serum magnesium values but normal urinary magnesium values. The typical clinical features are recurrent muscle cramps, episodes of tetany, tremor, and muscle weakness, especially in distal limbs. The disease is potentially fatal. The disease has only been described in one large Brazilian kindred with 46 family members, of whom 21 were affected. Caused by a N255D mutation in the KCNA1 gene (12p13), which encodes the voltage-gated potassium channel Kv1.1. Mutations in KCNA1 result in a nonfunctional channel protein, with a dominant negative effect on wild-type Kv1.1 channel function, which is involved in the maintenance of membrane voltage and optimal function of the TRPM6 channel. Transmission is autosomal dominant.
A form of peeling skin syndrome that presents with a generalised distribution. It comprises two sub-types: the non-inflammatory (PSS type A) and the inflammatory (PSS type B) forms.
A recently described syndrome with characteristics of developmental delay, short stature and facial dysmorphism. Dysmorphic features include bi-temporal narrowing, smooth philtrum, pointed chin and dysmorphic ears. All reported patients had a cleft palate, whereas congenital heart defects or epilepsy are observed in patients with large deletions. Deletions are located within chromosome band 15q14, distal to the Prader-Willi/Angelman region. They have a variable size with the smallest deletion being 1.6 Mb in length.
A recently described syndrome with characteristics of severe intellectual deficit, with a normal neonatal period, followed by a phase of regression at the age of 3-6 months. The phenotype includes other features: postnatal growth retardation and microcephaly, hypotonia, epilepsy, stereotypic movements and feeding problems. Dysmorphic features associate prominent metopic suture, bilateral epicanthic folds, bulbous nasal tip, tented upper lip, everted lower lip and large ears. This syndrome is caused by an interstitial deletion encompassing 14q12. They have a variable size and include FOXG1 as the gene responsible for the intellectual deficit and severe microcephaly.
The absence or dramatic reduction of circulating human serum albumin (HSA) with less than 50 cases reported in the literature so far. In the majority of cases the disorder is diagnosed in adulthood. Although albumin is the most abundant plasma protein and has many functions, patients present with only a few mild clinical signs and biochemical abnormalities, HSA is either absent or present at very low levels (<1 g/L) but liver function is normal and there is an absence of conditions leading to significant protein loss. The disorder appears to be more severe in the fetus or during early infancy. Transmitted as an autosomal recessive trait and consanguinity has been shown in all reported cases, the disorder is caused by homozygous or compound heterozygous mutations in the gene coding for HSA (ALB; 4q13.3).
This syndrome has characteristics of severe microcephaly, agyria, agenesis of the corpus callosum, cerebellar hypoplasia, facial dysmorphism and epiphyseal stippling of the metacarpal bones. It has been described in two brothers. The syndrome is transmitted as an autosomal recessive trait and may be an allelic variant of Neu-Laxova syndrome and Lissencephaly type III with cystic dilations of the cerebellum and fetal akinesia sequence.
This syndrome has characteristics of the association of microencephaly, agenesis of the corpus callosum, brainstem hypoplasia, cystic cerebellum and fetal akinesia sequence. Less than 10 cases have been described so far. The syndrome is transmitted as an autosomal recessive trait and may be an allelic variant of Neu-Laxova syndrome and lissencephaly type III with metacarpal bone dysplasia.
This syndrome has characteristics of short stature, hypopigmentation, coarse facies and frequent bronchopulmonary Streptococcus pneumoniae infections. To date, it has been described in four members of one family. Linkage analysis led to the identification of a homozygous deletion in the coding region of the ROBLD3 gene, resulting in reduced expression of the endosomal adaptor protein p14.
Mixed autoimmune haemolytic anaemia (mixed AIHA) is a type of autoimmune haemolytic anaemia defined by the presence of both warm and cold autoantibodies, which have a deleterious effect on red blood cells at either body temperature or at lower temperatures. Diagnosis is based on clinical or laboratory evidence of haemolytic anaemia and the detection of autoantibodies, usually both IgG and IgM, with the direct anti-globulin test (DAT) showing a pattern of IgG with complement C3, and the presence of cold agglutinins (IgM) in the serum at a significant titre. The disease responds to corticosteroids, and may be followed by remission, but usually runs a chronic course with intermittent exacerbations.
This syndrome has characteristics of the association of acanthosis nigricans, insulin resistance, severe muscle cramps and acral hypertrophy. At least five cases have been described in the literature so far. Enlargement of the kidneys was also reported in some cases. Transmission is autosomal recessive.
This syndrome has characteristics of hypertrophic cardiomyopathy, muscular hypotonia and the presence of lactic acidosis at birth. It has been described in two sisters (both of whom died within the first year of life) from a non-consanguineous Turkish family. The syndrome is caused by a homozygous point mutation in the exon 3A of the SLC25A3 gene encoding a mitochondrial membrane transporter.
A congenital abnormality in which the eyelids are absent and skin covers the ocular bulb, which is often microphthalmic. Six cases of complete bilateral cryptophthalmia have been described. Transmission is autosomal dominant.
Distal monosomy 6p is responsible for a distinct chromosome deletion syndrome with a recognisable clinical picture including intellectual deficit, ocular abnormalities, hearing loss, and facial dysmorphism. Pure deletions have been described in less than 10 patients. Breakpoints are within 6p24-pter subtelomeric bands.
A chromosomal anomaly involving terminal deletion of the long arm of chromosome 10 resulting in characteristics of facial dysmorphism, pre and postnatal growth retardation, cardiac and genital anomalies and developmental delay. Prevalence is unknown but around 40 cases have been described in the literature so far. Genital abnormalities have been mostly reported in males, psychomotor retardation (generally described as mild) was present in all reported cases. Distal monosomy 10q results from a subterminal 10q deletion with breakpoints in the 10q25 or 10q26 band leading to partial monosomy for the genes located in this area. Most of the reported cases involved de novo terminal deletions resulting from abnormal non-allelic homolog recombination during meiosis.
An extremely rare, sporadic form of Orofaciodigital syndrome with only a few reported cases and characteristics of facial (blepharophimosis, bulbous nasal tip, broad nasal bridge, downslanting palpebral fissures and low set ears) and skeletal (post-axial polydactyly and fusion of vertebrae) malformations along with severe intellectual disability, deafness and congenital heart defects.
This syndrome has characteristics of muscular hypotonia and ichthyosis. It has been described in four children from two consanguineous families. All the affected children died during early infancy, two from dilated cardiomyopathy. The syndrome is caused by a deficiency in dolichol kinase 1 (DK1), an enzyme involved in the de novo biosynthesis of dolichol phosphate. The mutations identified in the DK1 gene led to a 96 to 98% reduction in DK activity.
A primary microangiopathy confined to the skin with characteristics of multiple and widespread telangiectasia. It is a rare disorder with less than 20 cases reported in the literature to date. Most patients present in adulthood with symmetrical telangiectasia appearing on the lower extremities and later progressing to the trunk and upper extremities. Thought to be associated with collagen abnormalities in the skin microvasculature.
A variant of self-healing collodion baby with manifestation of the presence at birth of a collodion membrane only at the extremities. Only 2 cases were described in the literature. In both cases, the babies healed soon after birth. In one case, molecular analysis was performed that revealed mutations in the TGM1 gene encoding transglutaminase 1, an enzyme involved in the cornification of the stratum corneum.
Encompasses heterozygous overlapping microdeletions on chromosome 8q21.11 resulting in intellectual disability, facial dysmorphism comprising a round face, ptosis, short philtrum, Cupid's bow and prominent low-set ears, nasal speech and mild finger and toe anomalies. The prevalence is unknown but 8q21.11 microdeletion syndrome is rare. Microdeletions appear de novo or are inherited from affected parents in an autosomal dominant manner.
A very rare genetic vascular disease of autosomal recessive inheritance, described in less than 20 patients to date. The disease has manifestations of adult-onset (as early as the second decade of life) isolated calcification of the arteries of the lower extremities (including the iliac, femoral, and tibial arteries) as well as the capsule joints of the fingers, wrists, ankles and feet.
Potential for trauma to skin or mucous membranes caused by heat or extreme temperatures during operative procedure.
A platelet granule disorder with manifestation of thrombocytopenia with giant platelets resulting in increased propensity for bleeding.
A rare and isolated orofacial defect with manifestation of incomplete median clefts of both the lower lip (limited to the vermilion, with no muscle involvement) and upper lip (with muscle involvement), double labial frenulum and fusion of the upper gingival and upper labial mucosa (resulting in a shallow upper vestibular fold), in addition to poor dental alignment, and increased interdental distance between the lower and upper median incisors. Variable expressivity has been reported in an affected family.
An exceedingly rare autosomal recessive neurological disorder reported only in a few families so far. It has characteristics of the association of early onset achalasia (manifesting in infancy) with severe intracranial angiopathy that is consistent with Moyamoya angiopathy in most cases. Other variable associated manifestations include hypertension, Raynaud phenomenon and livedo reticularis.
An extremely rare form of corneal dystrophy with manifestation of variable patterns of opacification in the Bowman layer of the cornea that extend anteriorly into the epithelium with decreased to normal visual acuity. Onset is in the first to second decade of life. Patients develop painful erosions that are less severe than those in Reis-Bucklers corneal dystrophy and Thiel-Behnke corneal dystrophy. Visual acuity is normal or sometimes slightly decreased. The condition has a progressive course. An autosomal dominant pattern of inheritance has been reported.
A fusion protein immunotoxin consisting of a humanized, single-chain monoclonal antibody fragment specific for the epithelial cell adhesion molecule (EpCAM) conjugated with a truncated form of Pseudomonas exotoxin A with potential antineoplastic activity. Oportuzumab monatox binds to Ep-CAM-positive tumor cells, thereby delivering the Pseudomonas exotoxin A moiety specifically; the Pseudomonas exotoxin A moiety then inactivates elongation factor 2 (EF-2) through ADP ribosylation, resulting in inhibition of protein synthesis in target cells. EpCAM, a cell surface protein, is expressed by a variety of tumor cells and is frequently found in head and neck cancers.
An orally bioavailable, receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Upon administration, sitravatinib binds to and inhibits the activity of several RTKs including hepatocyte growth factor receptor (HGFR; c-Met; MET), tyrosine-protein kinase receptor UFO (AXL receptor tyrosine kinase; AXL), mast/stem cell growth factor receptor (SCFR; c-kit; KIT), the receptor tyrosine kinase MER, discoidin domain receptor 2 (DDR2), vascular endothelial growth factor receptor (VEGFR) types 1 (VEGFR-1; FLT1), 2 (VEGFR-2; KDR; Flk-1) and 3 (VEGFR-3), members of the platelet-derived growth factor receptor (PDGFR) family, RET (rearranged during transfection), tropomyosin-related kinases (TRK) and members of the ephrin (Eph) family of receptor tyrosine kinases. This may result in both the inhibition of signal transduction pathways mediated by these RTKs and the reduction of tumor cell proliferation in cancer cell types that overexpress these RTKs.
A second generation rexinoid and agonist of retinoid X receptor (RXR), with potential antineoplastic, neuroprotective, immunoregulatory, and disease-modifying activities. Upon administration, IRX4204 specifically binds to and activates RXRs, thereby activating RXR-mediated signaling pathways and inducing changes in gene expression that lead to cell differentiation. In responsive cancer cells, IRX4204 induces cell differentiation, decreases cell proliferation, and induces apoptosis, which leads to cancer regression. IRX4204 enhances the differentiation of CD4-positive T lymphocytes into inducible regulatory T cells (iTreg) and suppresses the development of inflammatory T helper 17 (Th17) cells. In addition, IRX4204 is able to cross the blood-brain barrier (BBB) and induces the differentiation of oligodendrocyte precursor cells (OPCs) into oligodendrocytes, promotes repair of myelin, and enhances the survival of dopaminergic neurons.
An orally bioavailable inhibitor of checkpoint kinase 1 (chk1), with potential antineoplastic and chemosensitization activities. Upon oral administration, chk1 inhibitor CCT245737 selectively binds to chk1, thereby preventing chk1 activity and abrogating the repair of damaged DNA. This may lead to an accumulation of damaged DNA, inhibition of cell cycle arrest, and induction of apoptosis. CCT245737 may potentiate the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapeutic agents. Chk1, an adenosine triphosphate (ATP)-dependent serine/threonine kinase overexpressed in a variety of cancer cell types, mediates cell cycle checkpoint control and is essential for DNA repair; it plays a key role in resistance to chemotherapeutic agents by repairing DNA damage.
Infantile hypercalcemia is characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. An epidemic of idiopathic infantile hypercalcemia occurred in the United Kingdom in the 1950s after the implementation of an increased prophylactic dose of vitamin D supplementation; however, the fact that most infants receiving the prophylaxis remained unaffected suggested that an intrinsic hypersensitivity to vitamin D might be implicated in the pathogenesis (summary by Schlingmann et al., 2011). Genetic Heterogeneity Infantile hypercalcemia-2 (HCINF2; 616963) is caused by mutation in the SLC34A1 gene (182309) on chromosome 5q35.
Infantile hypercalcemia is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis (summary by Schlingmann et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of infantile hypercalcemia, see HCINF1 (143880).
Autoinflammation, panniculitis, and dermatosis syndrome (AIPDS) is an autosomal recessive autoinflammatory disease characterized by neonatal onset of recurrent fever, erythematous rash with painful nodules, painful joints, and lipodystrophy. Additional features may include diarrhea, increased serum C-reactive protein, leukocytosis, and neutrophilia in the absence of any infection. Patients exhibit no overt primary immunodeficiency (Damgaard et al., 2016 and Zhou et al., 2016).
Intellectual developmental disorder with dysmorphic facies and ptosis is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, delayed language, and dysmorphic facial features, most notably ptosis/blepharophimosis. Additional features may include poor growth, hypotonia, and seizures (summary by Mattioli et al., 2017). See also chromosome 3p deletion syndrome (613792).
Hypotonia, ataxia, and delayed development syndrome (HADDS) is a neurodevelopmental syndrome characterized by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia. Some patients may have urogenital abnormalities (summary by Sleven et al., 2017).
Yao syndrome is an autoinflammatory disease characterized by periodic fever, dermatitis, arthritis, and swelling of the distal extremities, as well as gastrointestinal and sicca-like symptoms. The disorder is associated with specific NOD2 variants (and Shen, 2017).
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016).
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Patients with ASGD6 have been reported with the Peters anomaly subtype. Peters anomaly consists of corneal opacity, defects in the posterior structures of the cornea, and iridocorneal and/or keratolenticular adhesions. Over 50% of patients develop glaucoma in childhood (summary by Vincent et al., 2001).
MPSPS is an autosomal recessive inborn error of metabolism resulting in a multisystem disorder with features of the mucopolysaccharidosis lysosomal storage diseases (see, e.g., 607016). Patients present in infancy or early childhood with respiratory difficulties, cardiac problems, anemia, dysostosis multiplex, renal involvement, coarse facies, and delayed psychomotor development. Most patients die of cardiorespiratory failure in the first years of life (summary by Kondo et al., 2017).
OPA11 is an autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, ataxia, optic atrophy, and leukoencephalopathy on brain imaging. Laboratory studies are consistent with mitochondrial dysfunction (summary by Hartmann et al., 2016). For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (165500).
LMPHM7 is an autosomal dominant disorder with variable expressivity. Some patients may develop severe nonimmune lymphatic-related hydrops fetalis (LRHF) in utero, resulting in early death, whereas others may have milder manifestations, such as atrial septal defect (ASD) or varicose veins as adults. The hydrops and/or swelling improves spontaneously in those who survive the neonatal period (summary by Martin-Almedina et al., 2016).
Early-onset vitamin B6-dependent epilepsy is an autosomal recessive neurologic disorder characterized by onset of seizures in the neonatal period or first months of life. The seizures show favorable response to treatment with activated vitamin B6 (pyridoxal 5-prime-phosphate; PLP) and/or pyridoxine. However, most patients show delayed psychomotor development (summary by Darin et al., 2016).
KMT2B-related dystonia (DYT-KMT2B) is a complex childhood-onset (mean age 7 years) movement disorder described to date in 39 individuals. It is characterized by a progressive disease course evolving commonly from lower-limb focal dystonia into generalized dystonia with prominent cervical, cranial, and laryngeal involvement. Communication difficulties, secondary to articulation difficulties and low speech volume, are common. Bulbar dysfunction leads to impaired swallowing. Intellectual disability (ID) / developmental delay (DD) are commonly reported. Additional findings can include eye movement abnormalities, skin changes, psychiatric comorbidities (attention deficit hyperactivity disorder, anxiety, depression, and obsessive-compulsive disorder), myoclonus, seizures, spasticity, and sensorineural hearing loss. Many affected individuals follow a similar disease course, though milder and atypical findings have been described.
Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities is an autosomal recessive neurologic disorder characterized by onset of involuntary movements in the first decade of life. Optic atrophy develops around the same time or slightly later. Severity is variable, and some patients lose independent ambulation. Brain imaging shows abnormalities in the basal ganglia. Cognition appears to be unaffected (summary by Heimer et al., 2016).
Early infantile epileptic encephalopathy-49 is a severe autosomal recessive neurologic disorder characterized by onset of seizures in the neonatal period, global developmental delay with intellectual disability and lack of speech, hypotonia, spasticity, and coarse facial features. Some patients may have brain calcifications on imaging (summary by Han et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Early infantile epileptic encephalopathy-48 is a severe autosomal recessive neurologic disorder characterized by global developmental delay with intellectual disability and absent speech, poor, if any, motor development, and onset of seizures in the first year of life. Affected individuals have poor eye contact and may develop microcephaly and abnormal movements (summary by Assoum et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Nephronophthisis-20 is an autosomal recessive tubulointerstitial nephritis characterized by progressive renal fibrosis resulting in end-stage renal failure. The age at onset is relatively late compared to other forms of NPHP, and patients develop end-stage renal disease in the second or third decades. Unlike most other forms of NPHP, NPHP20 does not have features of a ciliopathy and patients do not appear to have extrarenal manifestations (summary by Macia et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of nephronophthisis, see NPHP1 (256100).
GDACCF is an intellectual disability syndrome apparent soon after birth with neonatal hypotonia, poor feeding, and respiratory insufficiency followed by delayed psychomotor development and intellectual disability with poor speech. Brain imaging shows aplasia or hypoplasia of the corpus callosum. Affected individuals have variable dysmorphic facial features, and some may have dysplastic, cystic kidneys or mild cardiac defects (summary by Stevens et al., 2016).
Myofibrillar myopathy-8 is an autosomal recessive myopathy characterized by childhood onset of slowly progressive proximal muscle weakness and atrophy resulting in increased falls, gait problems, and difficulty running or climbing stairs. Upper and lower limbs are affected, and some individuals develop distal muscle weakness and atrophy. Ambulation is generally preserved, and patients do not have significant respiratory compromise. Muscle biopsy shows a mix of myopathic features, including myofibrillar inclusions and sarcomeric disorganization (summary by O'Grady et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Lissencephaly-8 is an autosomal recessive neurologic disorder characterized by delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, and hypotonia. Brain imaging shows variable features, including cortical gyral abnormalities and hypoplasia of the corpus callosum, brainstem, and cerebellum (summary by Jerber et al., 2016). For a general description and a discussion of genetic heterogeneity lissencephaly, see LIS1 (607432).
Uncombable hair syndrome is characterized by silvery, blond, or straw-colored scalp hair that is dry, frizzy, and wiry, has a characteristic sheen, stands away from the scalp in multiple directions, and is impossible to comb. This hair shaft disorder occurs in children and improves with age. The hair growth rate can range from slow to normal (summary by U. Basmanav et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of UHS, see UHS1 (191480).
MGCA8 is an autosomal recessive metabolic disorder resulting in death in infancy. Features include hypotonia, abnormal movements, respiratory insufficiency with apneic episodes, and lack of developmental progress, often with seizures. Brain imaging is variable, but may show progressive cerebral atrophy. Laboratory studies show increased serum lactate and 3-methylglutaconic aciduria, suggesting a mitochondrial defect (summary by Mandel et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950).
LICS is an autosomal recessive chromosome breakage syndrome characterized by failure to thrive in infancy, immune deficiency, and fatal progressive pediatric lung disease induced by viral infection. Some patients may have mild dysmorphic features (summary by van der Crabben et al., 2016).
CRDHL1 is characterized by cone-rod dystrophy and sensorineural hearing loss, with relatively late onset of both ocular and hearing impairment. The funduscopic findings are characteristic, showing ring-shaped atrophy along the major vascular arcades that manifests on fundus autofluorescence as a hypoautofluorescent band along the vascular arcades surrounded by hyperautofluorescent borders (Namburi et al., 2016). Genetic Heterogeneity of Cone-Rod Dystrophy and Hearing Loss CRDHL2 (618358) is caused by mutation in the CEP250 gene (609689) on chromosome 20q11.
Neonatal intractable myoclonus is a severe neurologic disorder characterized by the onset of intractable myoclonic seizures soon after birth. Affected infants have intermittent apnea, abnormal eye movements, pallor of the optic nerve, and lack of developmental progress. Brain imaging shows a progressive leukoencephalopathy. Some patients may die in infancy. There is phenotypic and biochemical evidence of mitochondrial dysfunction (summary by Duis et al., 2016).
Autosomal recessive limb-girdle muscular dystrophy-21 (LGMDR21) is characterized by young-adult onset of slowly progressive proximal upper and lower limb muscle weakness and atrophy (summary by Servian-Morilla et al., 2016). For a discussion of genetic heterogeneity of autosomal recessive LGMD, see LGMDR1 (253600).
Combined oxidative phosphorylation deficiency-31 is an autosomal recessive multisystem disorder characterized by left ventricular noncompaction (LVNC), global developmental delay, and severe hypotonia. More variable features include seizures, cataract, and abnormal movements. The disorder becomes apparent soon after birth or in early infancy, and patients may die in early childhood. Biochemical studies are consistent with a defect in mitochondrial function (summary by Eldomery et al., 2016). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Autosomal recessive spastic paraplegia-78 is an adult-onset neurodegenerative disorder characterized predominantly by spasticity and muscle weakness of the lower limbs, resulting in gait difficulties and loss of ambulation in some patients. Affected individuals also have cerebellar signs, such as dysarthria, oculomotor disturbances, and limb and gait ataxia; brain imaging shows cerebellar atrophy. Some patients may have mild cognitive impairment or frank dementia. The phenotype is highly variable (summary by Estrada-Cuzcano et al., 2017). Biallelic mutation in the ATP13A2 gene also causes Kufor-Rakeb syndrome (KRS; 606693), a neurodegenerative disorder with overlapping features. Patients with KRS have earlier onset and prominent parkinsonism. Loss of ATP13A2 function results in a multidimensional spectrum of neurologic features reflecting various regions of the brain and nervous system, including cortical, pyramidal, extrapyramidal, brainstem, cerebellar, and peripheral (summary by Estrada-Cuzcano et al., 2017).
PEAMO is a severe autosomal recessive neurodegenerative disorder characterized by delayed development with hypotonia apparent in infancy and subsequent motor regression. Most affected individuals are unable to or lose the ability to sit and show distal amyotrophy and weakness of all 4 limbs. The patients are cognitively impaired and unable to speak or have severe dysarthria. Additional features include optic atrophy, thin corpus callosum, and cerebellar atrophy (summary by Sferra et al., 2016).
Autosomal visceral heterotaxy-8 is an autosomal recessive developmental disorder characterized by visceral situs inversus associated with complex congenital heart malformations caused by defects in the normal left-right asymmetric positioning of internal organs (summary by Vetrini et al., 2016). For a discussion of the genetic heterogeneity of visceral heterotaxy, see HTX1 (306955).
Periventricular nodular heterotopia-7 is a neurologic disorder characterized by abnormal neuronal migration during brain development resulting in delayed psychomotor development and intellectual disability; some patients may develop seizures. Other features include cleft palate and 2-3 toe syndactyly (summary by Broix et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of periventricular heterotopia, see 300049.
PEBAT is an autosomal recessive neurodevelopmental disorder characterized by severely delayed psychomotor development apparent soon after birth or in infancy, profound intellectual disability, poor or absent speech, and seizures. Most patients are never able to walk due to hypotonia or spasticity. Brain imaging shows cerebral and cerebellar atrophy, thin corpus callosum, and secondary hypomyelination. The disorder shows progressive features, including microcephaly, consistent with a neurodegenerative process (summary by Miyake et al., 2016; Flex et al., 2016).
Shashi-Pena syndrome is a neurodevelopmental syndrome characterized by delayed psychomotor development, variable intellectual disability, hypotonia, facial dysmorphism, and some unusual features, including enlarged head circumference, glabellar nevus flammeus, and deep palmar creases. Some patients may also have atrial septal defect, episodic hypoglycemia, changes in bone mineral density, and/or seizures (summary by Shashi et al., 2016).
Spermatogenic failure-16 is characterized by acephalic spermatozoa causing male infertility. Semen from affected men consistently shows nearly 100% abnormally shaped spermatozoa, mostly made up of headless tails, with a small proportion of intact spermatozoa with an abnormal head-tail junction, as well as a few tailless heads. Ultrastructurally, the anomaly involves absence of the implantation fossa and basal plate between the sperm head and the tail (summary by Zhu et al., 2016). For a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy (PEBEL) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, respiratory insufficiency, and seizures, resulting in coma and death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions (summary by Kremer et al., 2016).
MTDPS12A is characterized by severe hypotonia due to mitochondrial dysfunction apparent at birth. Affected infants have respiratory insufficiency requiring mechanical ventilation and have poor or no motor development. Many die in infancy, and those that survive have profound hypotonia with significant muscle weakness and inability to walk independently. Some patients develop hypertrophic cardiomyopathy. Muscle samples show mtDNA depletion and severe combined mitochondrial respiratory chain deficiencies (summary by Thompson et al., 2016). For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).
Harel-Yoon syndrome is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy. Other more variable features such as optic atrophy may also occur. Laboratory studies in some patients show evidence of mitochondrial dysfunction (summary by Harel et al., 2016).
LADCI is an autosomal recessive neurodevelopmental disorder characterized by severe expressive and receptive language delay apparent from early childhood. Affected individuals have additional developmental or behavioral abnormalities, including attention deficit, hyperactivity, or mild intellectual disability. Some patients develop cardiac arrhythmias reminiscent of sick sinus syndrome (summary by Lodder et al., 2016 and Shamseldin et al., 2016).
Chitayat syndrome is a rare condition characterized by respiratory distress presenting at birth, bilateral accessory phalanx resulting in shortened index fingers with ulnar deviation, hallux valgus, and characteristic facial features including prominent eyes, hypertelorism, depressed nasal bridge, full lips, and upturned nose (summary by Balasubramanian et al., 2017).
Intellectual developmental disorder with cardiac arrhythmia is an autosomal recessive multisystem disorder characterized by delayed psychomotor development, severe intellectual disability with poor or absent speech, and bradycardia and/or cardiac sinus arrhythmias. Additional features include visual abnormalities, seizures, hypotonia, and gastric reflux (summary by Lodder et al., 2016).
Early infantile epileptic encephalopathy-47 is a neurologic disorder characterized by onset of intractable seizures in the first days or weeks of life. EEG shows background slowing and multifocal epileptic spikes, and may show hypsarrhythmia. Most patients have developmental regression after seizure onset and show persistent intellectual disability and neurologic impairment, although the severity is variable. Treatment with phenytoin, a voltage-gated sodium channel blocker, may be beneficial (summary by Guella et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Sifrim-Hitz-Weiss syndrome is an autosomal dominant intellectual developmental disorder with variable congenital defects affecting other systems, including cardiac, skeletal, and urogenital. Some patients may have short stature, enlarged head circumference, hearing loss, and nonspecific dysmorphic facial features (summary by Sifrim et al., 2016 and Weiss et al., 2016).
Distal arthrogryposis with impaired proprioception and touch is an autosomal recessive neurologic disorder characterized by loss of certain mechanosensation modalities resulting in ataxia, difficulty walking, dysmetria, muscle weakness and atrophy, and progressive skeletal contractures. Patients have onset of symptoms in early childhood (summary by Chesler et al., 2016 and Delle Vedove et al., 2016).
Childhood-onset neurodegeneration with ataxia, dystonia, and gaze palsy is an autosomal recessive progressive disorder characterized by onset of gait ataxia, cognitive decline, and gaze palsy in the first or second decades. Additional features include dysarthria, dystonia, and athetoid movements. Some patients may become wheelchair-bound as young adults (summary by Haack et al., 2016).
Congenital myasthenic syndrome-20 is an autosomal recessive neuromuscular disorder characterized by severe hypotonia associated with episodic apnea soon after birth. Patients have muscle weakness resulting in delayed walking, ptosis, poor sucking and swallowing, and generalized limb fatigability and weakness. EMG studies usually show a decremental response to repetitive nerve stimulation, and some patients may show a good response to AChE inhibitors (summary by Bauche et al., 2016). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462).
ZTTK syndrome is a severe multisystem developmental disorder characterized by delayed psychomotor development and intellectual disability. Affected individuals have characteristic dysmorphic facial features, hypotonia, poor feeding, poor overall growth, and eye or visual abnormalities. Most patients also have musculoskeletal abnormalities, and some have congenital defects of the heart and urogenital system. Brain imaging usually shows developmental abnormalities such as gyral changes, cortical and/or cerebellar atrophy, and thin corpus callosum (summary by Kim et al., 2016).
Frontometaphyseal dysplasia (FMD) is a progressive sclerosing skeletal dysplasia characterized by supraorbital hyperostosis, undermodeling of the small bones, and small and large joint contractures, as well as extraskeletal developmental abnormalities, primarily of the cardiorespiratory system and genitourinary tract. Patients with FMD2 appear to have a propensity for keloid formation (summary by Wade et al., 2016). For a discussion of genetic heterogeneity of frontometaphyseal dysplasia, see FMD1 (305620).
BBS20 is an autosomal recessive ciliopathy described in a single patient and characterized by retinitis pigmentosa, obesity, polydactyly, hypogonadism, and intellectual disability (Lindstrand et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
Familial focal epilepsy with variable foci (FFEVF) is an autosomal dominant form of epilepsy characterized by focal seizures arising from different cortical regions, including the temporal, frontal, parietal, and occipital lobes. Seizure types commonly include temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and nocturnal frontal lobe epilepsy (NFLE). A subset of patients have structural brain abnormalities, particularly focal cortical dysplasia (FCD). There is significant incomplete penetrance, with many unaffected mutation carriers within a family (summary by Ricos et al., 2016). For a discussion of genetic heterogeneity of FFEVF, see FFEVF1 (604364).
Peeling skin syndrome-5 (PSS5) is characterized by superficial peeling of the dorsal and palmar skin of the hands and feet; the skin of the forearms and legs may also be involved. Some patients exhibit diffuse yellowish hyperkeratotic palmoplantar plaques (Pigors et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of peeling skin syndrome, see PSS1 (270300).
Myofibrillar myopathy-7 is an autosomal recessive muscle disorder characterized by early childhood onset of slowly progressive muscle weakness primary affecting the lower limbs and associated with joint contractures (summary by Straussberg et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Patterned macular dystrophy-3 (MDPT3), also called Martinique crinkled retinal pigment epitheliopathy, appears in the fourth or fifth decade of life and is characterized by a 'dry desert land' pattern of the fundus, involving the posterior pole initially and progressing from the temporal fovea to the periphery of the retina. Polypoid choroidal vasculopathy, choroidal neovascularization, or atrophic fibrous macular scarring can cause reduced visual acuity after age 50. Late-stage MDPT3 consists of a retinitis pigmentosa (RP; see 268000)-like phenotype due to death of retinal pigment epithelium (RPE) and photoreceptor cells. The dry desert land pattern observed on fundus examination corresponds to an irregular thickness of the Bruch membrane and the RPE, with a scalloped elevation ('crinkling') of the RPE observed on optical coherence tomography (OCT). Full-field electroretinography may be normal at preclinical and early stages of the dystrophy, but later cone and rod responses are severely reduced, consistent with progressive photoreceptor cell dysfunction and death at the final state (summary by Meunier et al., 2016). For a general phenotypic description and discussion of genetic heterogeneity of patterned macular dystrophy, see MDPT1 (169150).
Sessile serrated polyposis cancer syndrome (SSPCS) is a rare disorder characterized by the presence of multiple serrated polyps in the colon and an increased personal and familial risk of colorectal cancer. SSPCS is defined by the World Health Organization (WHO) as the presence of at least 5 sessile serrated polyps (also known as 'sessile serrated adenomas,' or SSAs) proximal to the sigmoid colon, with 2 or more that are greater than 10 mm in diameter; or any number of serrated polyps in a person with a first-degree relative with SSPCS; or more than 20 serrated polyps of any size, distributed throughout the colon. SSAs are found in 2% of average-risk individuals undergoing their first screening colonoscopy, and are estimated to be responsible for 20 to 35% of all colon cancers. SSAs exhibit somatic mutations in the BRAF gene (164757), or less commonly in the KRAS gene (190070), early in their development. Individuals with SSPCS have a lifetime risk of colon cancer as high as 54% and may have a strong personal or family history of extracolonic cancers; first-degree relatives have a 32% risk of developing multiple serrated polyps and a 5-fold increased risk of colon cancer. An increased risk of pancreatic cancer has also been observed (summary by Gala et al., 2014).
Thauvin-Robinet-Faivre syndrome is an autosomal recessive disorder characterized by generalized overgrowth, mainly of height, and mildly delayed psychomotor development with mild or severe learning difficulties. More variable features may include congenital heart defects, kidney abnormalities, and skeletal defects. Patients may have an increased risk for Wilms tumor (summary by Akawi et al., 2016).
Familial adenomatous polyposis-4 is an autosomal recessive tumor predisposition syndrome characterized by the development of multiple colonic adenomas in adulthood, often with progression to colorectal cancer. Proliferative lesions in other tissues may also occur (summary by Adam et al., 2016). For a discussion of genetic heterogeneity of familial adenomatous polyposis, see FAP1 (175100).
GRIDHH is an autosomal recessive multisystem disorder characterized by poor overall growth, impaired intellectual development, hypotonia, and variable liver dysfunction. Additional features, such as seizures and hearing loss, may also be present (summary by Kopajtich et al., 2016).
Primary ciliary dyskinesia-35 is an autosomal recessive disorder characterized by recurrent upper and lower respiratory infections due to defective ciliary function. Examination of respiratory cilia shows lack of outer dynein arms (ODAs) and immotile cilia. Some patients may have laterality defects (summary by Wallmeier et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Primary ciliary dyskinesia-34 (CILD34) is an autosomal recessive disorder characterized by childhood onset of recurrent sinopulmonary infections due to impaired ciliary function. Affected males are infertile due to impaired sperm function and viability. Laterality defects have not been observed in this type of CILD (summary by El Khouri et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Autosomal recessive primary microcephaly-17 (MCPH17) is a severe neurologic disorder characterized by very small head circumference that is apparent at birth and worsens over time (up to -12 SD). Affected individuals have delayed psychomotor development, intellectual disability, spasticity, axial hypotonia, and dysmorphic features. Brain imaging shows a simplified gyral pattern; more severe cases have lissencephaly with hypoplasia of the brainstem and cerebellum (summary by Harding et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200).
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). SRTD15 is characterized by narrow thorax, oral and cardiovascular anomalies, short long bones, and postaxial polydactyly, in addition to other congenital anomalies. Considerable variability in features and in severity has been reported, with some affected individuals succumbing shortly after birth and others living to adulthood, even within the same family. For a discussion of genetic heterogeneity of short-rib thoracic dysplasia with or without polydactyly, see SRTD1 (208500).
Autosomal recessive axonal CMT2A2B is a neurologic disorder characterized by onset of peripheral neuropathy in the first years of life. Patients have difficulty walking due to distal muscle weakness; upper limbs may also be affected. Sensory impairment is more variable. Patients often have optic atrophy (summary by Polke et al., 2011).
Encephalopathy due to defective mitochondrial and peroxisomal fission-2 is an autosomal recessive disorder characterized by delayed psychomotor development, severe hypotonia with inability to walk, microcephaly, and abnormal signals in the basal ganglia. More variable features include early-onset seizures, optic atrophy, and peripheral neuropathy (summary by Koch et al., 2016). For a discussion of genetic heterogeneity of EMPF, see EMPF1 (614388).
Benign familial infantile seizures-5 (BFIS5) is an autosomal dominant neurologic disorder characterized by onset of afebrile seizures during infancy. In most cases, the seizures remit by age 2 years, although some patients may have single or a few seizures later in childhood. The seizures respond well to treatment with sodium channel blockers, and patients have normal subsequent psychomotor development. Some patients may develop paroxysmal kinesigenic dyskinesia around puberty (summary by Gardella et al., 2016 and Anand et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of benign familial infantile seizures, see BFIS1 (601764).
Nasopharyngeal carcinoma (NPCA) is a malignant tumor that emerges from the epithelium of the nasopharynx. It has a high incidence in southern China, and evidence suggests that there may be a genetic component that underlies familial clustering. Some patients have onset before 20 years of age (summary by Dai et al., 2016) For a general phenotypic description and a discussion of genetic heterogeneity of susceptibility to nasopharyngeal carcinoma, see NPCA1 (607107).
Autosomal recessive myopathy with rigid spine and distal joint contractures (MRRSDC) is characterized by onset of slowly progressive muscle weakness in the first or second decades of life. There is initial involvement of the proximal lower limbs, followed by distal upper and lower limb muscle weakness and atrophy. Other features include joint contractures, rigid spine, and restricted pulmonary function; some patients may have mild cardiac involvement (summary by Kayman-Kurekci et al., 2014).
Autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-4 (PEOB4) is an autosomal recessive disorder characterized by adult onset of eye muscle weakness and proximal limb muscle weakness associated with deletions of mtDNA on skeletal muscle biopsy, which results from defective mtDNA replication in post-mitotic muscle tissue. Additional features are more variable (summary by Ronchi et al., 2012). For a discussion of genetic heterogeneity of autosomal recessive PEO, see PEOB1 (258450).
Noncirrhotic portal hypertension is an autosomal recessive disorder characterized by onset of portal hypertension associated with hepatosplenomegaly in the first or second decades of life, in the absence of cirrhosis, known extrahepatic diseases, or splanchnic venous thrombosis. Liver function is normal, and the disorder is relatively benign (Vilarinho et al., 2016).
Okur-Chung neurodevelopmental syndrome is an autosomal dominant disorder characterized by delayed psychomotor development, intellectual disability with poor speech, behavioral abnormalities, cortical malformations in some patients, and variable dysmorphic facial features. Additional features, including microcephaly, gastrointestinal problems, and low levels of immunoglobulins, may be observed in some patients (Okur et al., 2016).
TRIO-related intellectual disability (ID) is characterized by delay in acquisition of motor and language skills, mild to borderline intellectual disability, and neurobehavioral problems (including autistic traits or autism spectrum disorder, attention deficit hyperactivity disorder, and/or aggression). Neonatal or infantile feeding difficulties including poor suck, impaired bottle feeding, and failure to thrive are common and are often the presenting finding. Other findings can include microcephaly, variable hand and dental abnormalities, and suggestive facial features. Only ten of the 20 individuals with a TRIO pathogenic variant reported to date had sufficient information to make preliminary generalizations about clinical manifestations; it is anticipated that the phenotype of this newly described disorder will continue to evolve.
Crisponi/cold-induced sweating syndrome-3 is an autosomal recessive disorder characterized by infantile-onset hyperthermia and abnormal paroxysmal contractions of the facial and oropharyngeal muscles, resulting in feeding and respiratory difficulties. Other features include joint contractures and camptodactyly. Death in infancy may occur, and those that survive may develop retinitis pigmentosa later in childhood. Individuals with some forms of Crisponi syndrome may develop paradoxical cold-induced sweating later in childhood, although this is a variable finding (summary by Angius et al., 2016). For a discussion of genetic heterogeneity of Crisponi/cold-induced sweating syndrome, see CISS1 (272430).
Bone marrow failure syndrome-3 is an autosomal recessive disorder characterized by onset of pancytopenia in early childhood. Patients may have additional variable nonspecific somatic abnormalities, including poor growth, microcephaly, and skin anomalies (summary by Tummala et al., 2016). BMFS3 has a distinct phenotype and may include features that overlap with Shwachman-Diamond syndrome (SDS1; 260400), such as pancreatic insufficiency and short stature, and with dyskeratosis congenita (see, e.g., DKCA1, 127550), such as dental and hair abnormalities and shortened telomeres. In addition, some patients may have joint and skeletal abnormalities, impaired development, and retinal dysplasia (summary by D'Amours et al., 2018). For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675).
Progressive familial intrahepatic cholestasis-5 (PFIC5) is an autosomal recessive severe liver disorder characterized by onset of intralobular cholestasis in the neonatal period. The disease is rapidly progressive, leading to liver failure and death if liver transplant is not performed. Other features include abnormal liver enzymes, low to normal gamma-glutamyl transferase (GGT) activity, increased alpha-fetoprotein, and a vitamin K-independent coagulopathy (summary by Gomez-Ospina et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of PFIC, see PFIC1 (211600).
Duane retraction syndrome is the most common congenital disorder of cranial dysinnervation, with a prevalence of 1 in 1,000 individuals. Affected individuals have limited unilateral or bilateral horizontal eye movement, accompanied by globe retraction and palpebral fissure narrowing on attempted adduction (movement of the eye inward, toward the nose). DURS can be classified into 3 types: type 1, the most common, involves limited abduction (movement of the eye outward toward the ear); type 2, the least common, involves limited adduction; and type 3 involves limitation of both abduction and adduction. MRI and postmortem examination of patients with DURS have shown absence or hypoplasia of the abducens nerve, which normally innervates the lateral rectus (LR) extraocular muscle to abduct the eye, as well as aberrant LR muscle innervation by axons of the oculomotor nerve, which normally innervates the medial, inferior, and superior rectus and inferior oblique extraocular muscles (summary by Park et al., 2016). For a discussion of genetic heterogeneity of Duane retraction syndrome, see DURS1 (126800).
The ductus arteriosus is a vital in utero vascular connection between the aorta and pulmonary artery that allows right ventricular output to bypass the nonventilated fetal lungs. Postnatal closure of the ductus arteriosus is an important step in normal cardiopulmonary transition. Failure of ductal closure results in patent ductus arteriosus (PDA), which occurs in approximately 2 to 8 per 10,000 term infants and constitutes 5% to 7% of all congenital heart defects (summary by Hajj and Dagle, 2012). For a discussion of genetic heterogeneity of isolated PDA, see PDA1 (607411).
Distal myopathy-5 is an autosomal recessive, slowly progressive muscle disorder characterized by adolescent onset of distal muscle weakness and atrophy predominantly affecting the lower limbs. Other features include facial weakness and hyporeflexia. Patients remain ambulatory even after long disease duration (summary by Park et al., 2016).
Pontocerebellar hypoplasia type 2F is an autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly and variable neurologic signs and symptoms, including cognitive and motor delay, poor or absent speech, seizures, and spasticity (summary by Breuss et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (277470).
Congenital stationary night blindness type 1H (CSNB1H) is an unusual and unique stationary retinal disorder with a dual anomaly in visual processing, characterized by a partial or severe degree of ON bipolar dysfunction and variably reduced cone sensitivity. Patients present with childhood-onset night blindness and middle age-onset photophobia, but have near-normal vision and do not exhibit nystagmus or high myopia (Vincent et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of congenital stationary night blindness, see CSNB1A (310500).
Spinocerebellar ataxia-43 is an autosomal dominant, slowly progressive neurologic disorder characterized by adult-onset gait and limb ataxia and often associated with peripheral neuropathy mainly affecting the motor system, although some patients may have distal sensory impairment (summary by Depondt et al., 2016). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Severe congenital neutropenia-7 is an autosomal recessive immunodeficiency characterized by onset of recurrent infections in infancy or early childhood. Patients have peripheral neutropenia, although bone marrow biopsy shows normal granulocyte maturation. The neutropenia is not responsive to treatment with G-CSF, but may be responsive to GM-CSF (summary by Triot et al., 2014 and Klimiankou et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).
SLC39A14 deficiency is characterized by evidence between ages six months and three years of delay or loss of motor developmental milestones (e.g., delayed walking, gait disturbance). Early in the disease course, children show axial hypotonia followed by dystonia, spasticity, dysarthria, bulbar dysfunction, and signs of parkinsonism including bradykinesia, hypomimia, and tremor. By the end of the first decade they develop severe, generalized, pharmaco-resistant dystonia, limb contractures, and scoliosis, and lose independent ambulation. Cognitive impairment appears to be less prominent than motor disability. Some affected children have succumbed in their first decade due to secondary complications such as respiratory infections.
Macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR) is an autosomal recessive neurodevelopmental disorder characterized by large head and somatic overgrowth apparent at birth followed by global developmental delay. Affected individuals have characteristic dysmorphic facial features and persistently large head, but increased birth weight normalizes with age. Additional neurologic features, including seizures, hypotonia, and gait ataxia, may also occur. Patients show severe intellectual impairment (summary by Ortega-Recalde et al., 2015).
PCLD2 is an autosomal dominant disease characterized by the presence of multiple liver cysts resulting from structural changes in the biliary tree during development. Abnormal biliary structures may be present early in life, but they usually remain asymptomatic until cyst growth initiates during adulthood. In advanced stages, patients may develop massively enlarged livers, which cause a spectrum of clinical features and complications. Genetic studies suggest that an accumulation of somatic hits in cyst epithelium determines the rate of cyst formation. A subset of patients (28-35%) may develop kidney cysts that are usually incidental findings and do not result in clinically significant renal disease (review by Cnossen and Drenth, 2014). For a discussion of genetic heterogeneity of polycystic liver disease, see PCLD1 (174050).
Early infantile epileptic encephalopathy-37 is an autosomal recessive severe epileptic-dyskinetic disorder characterized by onset of intractable seizures or abnormal movements in the first years of life. Affected individuals show global developmental delay and/or developmental regression after onset of seizures. Patients also show a hyperkinetic movement disorder with choreoathetosis, spasticity, and rigidity. The individuals are severely affected, with mental retardation, absent speech, and impaired volitional movements (summary by Madeo et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
HIVEP2-related intellectual disability is a neurological disorder characterized by moderate to severe developmental delay and intellectual disability and mild physical abnormalities (dysmorphic features). Early symptoms of the condition include weak muscle tone (hypotonia) and delayed development of motor skills, such as sitting, standing, and walking. After learning to walk, many affected individuals continue to have difficulty with this activity; their walking style (gait) is often unbalanced and wide-based. Speech is also delayed, and some people with this condition never learn to talk. Most people with HIVEP2-related intellectual disability also have unusual physical features, such as widely spaced eyes (hypertelorism), a broad nasal bridge, or fingers with tapered ends, although there is no characteristic pattern of such features among affected individuals. Many people with the condition exhibit behavioral problems, such as hyperactivity, attention deficit disorder, aggression, anxiety, and autism spectrum disorder, which is a group of developmental disorders characterized by impaired communication and social interaction.Other features of HIVEP2-related intellectual disability include mild abnormalities in the structure of the brain and an abnormally small brain and head size (microcephaly). Less common health problems include seizures; recurrent ear infections; and eye disorders, such as eyes that do not look in the same direction (strabismus), ""lazy eye"" (amblyopia), and farsightedness (hyperopia). Some people with HIVEP2-related intellectual disability have gastrointestinal problems, which can include backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and constipation.
RERE-related disorders are characterized by neurodevelopmental problems with or without structural anomalies of the eyes, heart, kidneys, and genitourinary tract and mild sensorineural hearing loss. Hypotonia and feeding problems are common among affected individuals. Developmental delay and intellectual disability range from mild to profound. Behavior problems may include attention-deficit/hyperactivity disorder, self-injurious behavior, and autism spectrum disorder. A variety of eye anomalies (coloboma, optic nerve anomalies, microphthalmia, and/or Peter's anomaly) and vision issues (myopia, anisometropia, astigmatism, exotropia, esotropia) have been reported. Congenital heart defects, most commonly septal defects, have also been described. Genitourinary abnormalities include vesicoureteral reflux, and cryptorchidism and hypospadias in males. Sensorineural hearing loss can be unilateral or bilateral.
Autosomal dominant mental retardation-42 is a neurodevelopmental disorder characterized by global developmental delay and intellectual disability. More variable features include hypotonia, often later associated with limb hypertonia, seizures of various types, and poor overall growth. Strabismus, cortical visual impairment, and autistic features may also be present (summary by Petrovski et al., 2016).
Autosomal dominant deafness-70 is a form of nonsyndromic sensorineural hearing loss. Hearing impairment shows postlingual onset and is slowly progressive (Gao et al., 2015).
TRNT1 deficiency is a condition that affects many body systems. Its signs and symptoms can involve blood cells, the immune system, the eyes, and the nervous system. The severity of the signs and symptoms vary widely.A common feature of TRNT1 deficiency is a blood condition called sideroblastic anemia, which is characterized by a shortage of red blood cells (anemia). In TRNT1 deficiency, the red blood cells that are present are unusually small (erythrocytic microcytosis). In addition, developing red blood cells in the bone marrow (erythroblasts) can have an abnormal buildup of iron that appears as a ring of blue staining in the cell after treatment in the lab with certain dyes. These abnormal cells are called ring sideroblasts.Many people with TRNT1 deficiency have an immune system disorder (immunodeficiency) that can lead to recurrent bacterial infections. Repeated infections can cause life-threatening damage to internal organs. The immunodeficiency is characterized by low numbers of immune system cells called B cells, which normally help fight infections by producing immune proteins called antibodies (or immunoglobulins). These proteins target foreign invaders such as bacteria and viruses and mark them for destruction. In many individuals with TRNT1 deficiency, the amount of immunoglobulins is also low (hypogammaglobulinemia).In addition, many individuals with TRNT1 deficiency have recurrent fevers that are not caused by an infection. These fever episodes are often one of the earliest recognized symptoms of TRNT1 deficiency, usually beginning in infancy. The fever episodes are typically accompanied by poor feeding, vomiting, and diarrhea, and can lead to hospitalization. In many affected individuals, the episodes occur regularly, arising approximately every 2 to 4 weeks and lasting 5 to 7 days, although the frequency can decrease with age.Eye abnormalities, often involving the light-sensing tissue at the back of the eye (the retina), can occur in people with TRNT1 deficiency. Some of these individuals have a condition called retinitis pigmentosa, in which the light-sensing cells of the retina gradually deteriorate. Eye problems in TRNT1 deficiency can lead to vision loss.Neurological problems are also frequent in TRNT1 deficiency. Many affected individuals have delayed development of speech and motor skills, such as sitting, standing, and walking, and some have low muscle tone (hypotonia).Features that occur less commonly in people with TRNT1 deficiency include hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss), recurrent seizures (epilepsy), and problems with the kidneys or heart.TRNT1 deficiency encompasses what was first thought to be two separate disorders, a severe disorder called sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) and a milder disorder called retinitis pigmentosa with erythrocytic microcytosis (RPEM), each named for its most common features. SIFD begins in infancy, and affected individuals usually do not survive past childhood. RPEM, on the other hand, is recognized in early adulthood, and the microcytosis usually does not cause any health problems. However, it has since been recognized that some individuals have a combination of features that fall between these two ends of the severity spectrum. All of these cases are now considered part of TRNT1 deficiency.
Autosomal recessive spinocerebellar ataxia-23 is a neurologic disorder characterized by epilepsy, intellectual disability, and gait ataxia (summary by Gomez-Herreros et al., 2014).
Premature ovarian failure-11 (POF11) is characterized by secondary amenorrhea and hypergonadotropic ovarian insufficiency, with elevated serum follicle-stimulating hormone (FSH; see 136530) levels before age 40 years (Qin et al., 2015). For a general phenotypic description and discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360).
Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly (summary by Wieczorek et al., 2013). Patients with SMARCE1 mutations have a wide spectrum of manifestations, including severe to moderate intellectual disability and heart defects (summary by Kosho et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Thrombocytopenia-6 is an autosomal dominant hematologic disorder characterized by increased bleeding episodes due to reduced platelet count and abnormal platelet morphology resulting from defective megakaryopoiesis. Patients may also have bone abnormalities, including osteoporosis or tooth loss, as well as an increased risk for myelofibrosis (summary by Turro et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of thrombocytopenia, see 313900.
Axonal Charcot-Marie-Tooth disease type 2CC is an autosomal dominant peripheral neuropathy that predominantly affects the lower limbs, resulting in muscle weakness and atrophy and gait impairment. Other features include distal sensory impairment and less severe involvement of the upper limbs. The age at onset and severity are variable (summary by Rebelo et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (118210).
Autosomal dominant striatal degeneration-2 is a neurologic disorder characterized by hyperkinetic movements, mainly chorea, resulting from dysfunction of the basal ganglia. Although symptoms appear in the first decade, the disorder is not progressive (summary by Mencacci et al., 2016). For a discussion of genetic heterogeneity of ADSD, see ADSD1 (609161).
Infantile-onset limb and orofacial dyskinesia is an autosomal recessive neurologic disorder characterized by delayed motor development and onset of a hyperkinetic movement disorder in the first year of life. The disorder results in impaired walking and orofacial dyskinesia with difficulty talking; the severity is variable (summary by Diggle et al., 2016).
Heart and brain malformation syndrome is a severe autosomal recessive multiple congenital anomaly syndrome characterized by profoundly delayed psychomotor development, dysmorphic facial features, microphthalmia, cardiac malformations, mainly septal defects, and brain malformations, including Dandy-Walker malformation (summary by Shaheen et al., 2016).
Autosomal recessive mental retardation-53 is a neurodevelopmental disorder characterized by severely delayed psychomotor development, hypotonia apparent since infancy, and early-onset seizures in most patients. Some patients may have additional features, such as cerebellar hypoplasia and ataxia. MRT53 is one of a group of similar neurologic disorders resulting from biochemical defects in the glycosylphosphatidylinositol (GPI) biosynthetic pathway (summary by Makrythanasis et al., 2016). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
The marfanoid-progeroid-lipodystrophy syndrome (MFLS) is characterized by congenital lipodystrophy, premature birth with an accelerated linear growth disproportionate to weight gain, and progeroid appearance with distinct facial features, including proptosis, downslanting palpebral fissures, and retrognathia. Other characteristic features include arachnodactyly, digital hyperextensibility, myopia, dural ectasia, and normal psychomotor development (Takenouchi et al., 2013). Takenouchi et al. (2013) noted phenotypic overlap with Marfan syndrome (154700) and Shprintzen-Goldberg craniosynostosis syndrome (182212).
Immunodeficiency-centromeric instability-facial anomalies syndrome-4 is an autosomal recessive disorder characterized by recurrent infections in childhood and variable dysmorphic facial features. Laboratory studies show hypomethylation of certain chromosomal regions. Additional features, including delayed development, are variable (summary by Thijssen et al., 2015). For a discussion of genetic heterogeneity of immunodeficiency-centromeric instability-facial anomalies syndrome, see ICF1 (242860).
Immunodeficiency-centromeric instability-facial anomalies syndrome-3 is an autosomal recessive disorder characterized by recurrent infections in childhood and variable dysmorphic facial features. Laboratory studies show hypomethylation of certain chromosomal regions. Additional features, including delayed development, are variable (summary by Thijssen et al., 2015). For a discussion of genetic heterogeneity of immunodeficiency-centromeric instability-facial anomalies syndrome, see ICF1 (242860).
Spastic paraplegia-76 is an autosomal recessive neurologic disorder characterized by young-adult onset of slowly progressive spasticity of the lower limbs resulting in gait difficulties. Most affected individuals have upper limb involvement and additional features such as foot deformities and dysarthria. Cognition is unaffected (summary by Gan-Or et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Immunodeficiency-51 is an autosomal recessive primary immune deficiency that is usually characterized by onset of chronic mucocutaneous candidiasis in the first years of life. Most patients also show recurrent Staphylococcal skin infections, and may show increased susceptibility to chronic bacterial respiratory infections. Patient cells show a lack of cellular responses to stimulation with certain IL17 isoforms, including IL17A (603149), IL17F (606496), IL17A/F, and IL17E (IL25; 605658) (summary by Levy et al., 2016).
The 15q24 microdeletion syndrome is characterized by global developmental delay; mild to severe (usually at least moderate) intellectual disability; facial dysmorphisms; congenital malformations of the hands and feet, eye, and genitalia; joint laxity; and growth retardation and failure to thrive. Less common findings include: seizures; conductive and sensorineural hearing loss; hypospadias and/ or micropenis. Males and females are affected equally.
Bartter syndrome refers to a group of disorders that are unified by autosomal recessive transmission of impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and hypercalciuria. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb (TAL) of the Henle loop, where 30% of filtered salt is normally reabsorbed (Simon et al., 1997). Patients with antenatal (or neonatal) forms of Bartter syndrome (e.g., BARTS1, 601678) typically present with premature birth associated with polyhydramnios and low birth weight and may develop life-threatening dehydration in the neonatal period. Patients with classic Bartter syndrome present later in life and may be sporadically asymptomatic or mildly symptomatic (summary by Simon et al., 1996 and Fremont and Chan, 2012). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364.
Autosomal dominant striatal degeneration is a neurologic disorder characterized by variable movement abnormalities due to dysfunction in the striatal part of the basal ganglia (summary by Kuhlenbaumer et al., 2004). Genetic Heterogeneity of Autosomal Dominant Striatal Degeneration See also ADSD2 (616922), caused by mutation in the PDE10A gene (610652) on chromosome 6q27.
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Patients with ASGD5 have been reported with the Peters anomaly, Axenfeld anomaly, and Rieger anomaly subtypes. Peters anomaly consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea (Peters, 1906). It occurs as an isolated ocular abnormality or in association with other ocular defects. In Axenfeld anomaly, strands of iris tissue attach to the Schwalbe line; in Rieger anomaly, in addition to the attachment of iris tissue to the Schwalbe line, there is clinically evident iris stromal atrophy with hole or pseudo-hole formation and corectopia (summary by Smith and Traboulsi, 2012).
Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis is an X-linked recessive disorder with onset of features in early childhood. Anemia is sometimes present. Some patients may show mild early motor or speech delay, but cognition is normal (summary by Andreoletti et al., 2017).
IMD50 is an X-linked recessive primary immunodeficiency characterized by the onset of recurrent bacterial or varicella zoster virus (VZV) infections in early childhood. Laboratory studies show profound lymphopenia, hypogammaglobulinemia, poor immune response to vaccine antigens, and fluctuating neutropenia. The disorder does not affect overall patient survival (summary by Lagresle-Peyrou et al., 2016).
MRXSB is an X-linked dominant neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with behavioral abnormalities, and dysmorphic facial features. Additional variable features include musculoskeletal abnormalities, seizures, acquired microcephaly, and feeding problems with poor overall growth. Only females are affected (summary by Bain et al., 2016).
Congenital bilateral absence of the vas deferens (CBAVD) is found in more than 25% of men with obstructive azoospermia, involving a complete or partial defect of the Wolffian duct derivatives. In 80% of men with CBAVD (see 277180), mutations are identified in the CFTR gene (602421). The forms caused by mutations in the CFTR and ADGRG2 genes are clinically indistinguishable (summary by Patat et al., 2016).
Immunodeficiency-47 is an X-linked recessive complex immunodeficiency syndrome characterized by recurrent bacterial infections, hypogammaglobulinemia, liver dysfunction, and defective glycosylation of serum proteins. Some patients may also have neurologic abnormalities (summary by Jansen et al., 2016).
Antenatal Bartter syndrome is a potentially life-threatening disease characterized by fetal polyuria, polyhydramnios, prematurity, and postnatal polyuria with persistent renal salt wasting. In transient antenatal Bartter syndrome-5, the onset of polyhydramnios and labor occur several weeks earlier than in other forms of Bartter syndrome. Polyuria lasts from a few days to 6 weeks, ending around 30 to 33 weeks of gestational age. Other features in the neonatal period include hypercalciuria, causing nephrocalcinosis in some cases, as well as hyponatremia, hypokalemia, and elevated renin and aldosterone; these subsequently resolve or normalize, although nephrocalcinosis may persist (Laghmani et al., 2016).
Inherited abnormalities in the level of serum TBG have been classified as complete deficiency (TBG-CD), partial deficiency (TBG-PD), and excess (TBG-E). Patients are euthyroid (summary by Mori et al., 1995).
Lipid storage myopathy due to FLAD1 deficiency is an autosomal recessive inborn error of metabolism that includes variable mitochondrial dysfunction. The phenotype is extremely heterogeneous: some patients have a severe disorder with onset in infancy and cardiac and respiratory insufficiency resulting in early death, whereas others have a milder course with onset of muscle weakness in adulthood. Some patients show significant improvement with riboflavin treatment (summary by Olsen et al., 2016).
Intellectual developmental disorder with persistence of fetal hemoglobin is characterized by delayed psychomotor development, intellectual disability, variable dysmorphic features, including microcephaly, downslanting palpebral fissures, strabismus, and external ear abnormalities, and asymptomatic persistence of fetal hemoglobin (HbF) (summary by Dias et al., 2016). Many of these features overlap with chromosome 2p16.1-p15 deletion syndrome (612513).
GLYT1 encephalopathy is characterized in neonates by severe hypotonia, respiratory failure requiring mechanical ventilation, and absent neonatal reflexes; encephalopathy, including impaired consciousness and unresponsiveness, may be present. Arthrogryposis or joint laxity can be observed. Generalized hypotonia develops later into axial hypotonia with limb hypertonicity and a startle-like response to vocal and visual stimuli which should not be confused with seizures. To date, three of the six affected children reported from three families died between ages two days and seven months; the oldest reported living child is severely globally impaired at age three years. Because of the limited number of affected individuals reported to date, the phenotype has not yet been completely described.
Proximal chromosome 19q13.11 deletion syndrome is an autosomal dominant neurodevelopmental disorder characterized by delayed development, intellectual disability with poor speech, feeding difficulties, and autistic features. Some patients may have additional features, including renal tract anomalies (summary by Caubit et al., 2016).
Distal chromosome 19q13.11 deletion syndrome is an autosomal dominant neurodevelopmental disorder characterized by poor overall growth, slender habitus, microcephaly, delayed development, intellectual disability with poor or absent speech, and feeding difficulties. Additional features include dysmorphic facies, signs of ectodermal dysplasia, hand and foot anomalies, and genitourinary anomalies, particularly in males (summary by Chowdhury et al., 2014).
Xq25 duplication syndrome is an X-linked neurodevelopmental disorder characterized by delayed development and intellectual disability associated with abnormal behavior and dysmorphic facial features. Additional variable features may include thin corpus callosum on brain imaging and sleep disturbances. Carrier females may be mildly affected (summary by Leroy et al., 2016).
An increased concentration of sedoheptulose in the urine. Sedoheptulose is a monosaccharide with seven carbon atoms and a ketone functional group.
Partial or complete wasting (loss) of hippocampus tissue that was once present. []
A moderate form of myopia with refractive error of between -3.00 and -6.00 diopters. []
A decrease in the amount of alveolar bone around the root of a tooth.
An autosomal dominant form of Kenny-Caffey Syndrome due to mutation(s) in the FAM111A gene, encoding protein FAM111A. This condition is characterized by transient hypocalcemia, delayed closure of the anterior fontanel, eye anomalies, including microphthalmia, proportionate short stature, and cortical thickening and medullary stenosis of the tubular bones.
An abnormality of the intestine. The closely related term enteropathy is used to refer to any disease of the intestine. [HPO:probinson]
Loss and redistribution of subcutaneous and/or visceral adipose tissue from specific regions of the body.
Multiple biliary hamartomas are a rare clinicopathologic entity, consisting of small (less than 1.5cm), usually multiple and nodular cystic lesions in the liver.
A cerebral ependymoma that occurs during childhood.
An embryonal tumor with multilayered rosettes, C19MC-altered that arises from the supratentorial brain and occurs in children.
An abnormality of the nasal septum. [HPO:probinson]
A usually inherited blood coagulation disorder characterized by the partial or complete absence of fibrinogen in the blood, resulting in bleeding.
A usually aggressive malignant neoplasm arising from tooth-forming tissues. It more often affects older females and more frequently occurs in the mandible. It is characterized by the presence of malignant epithelial cells with clear cytoplasm and a fibrotic stroma formation. It may recur and metastasize. Metastases may occur in the lymph nodes, lungs, and bones. Treatment of choice is resection with clean margins.
Any abnormality of the eye, including location, spacing, and intraocular abnormalities.
This term refers to the loss of eyelashes that were previously present. [HPO:probinson]
An accumulation of blood between the neurosensory retina and the retinal pigment epithelium (RPE) arising from the choroidal or retinal circulation.
If you take a medicine in a way that is different from what the doctor prescribed, it is called prescription drug abuse. It could be. -Taking a medicine that was prescribed for someone else. -Taking a larger dose than you are supposed to. -Taking the medicine in a different way than you are supposed to. This might be crushing tablets and then snorting or injecting them. -Using the medicine for another purpose, such as getting high. Abusing some prescription drugs can lead to addiction. These include opioids, sedatives, tranquilizers, and stimulants. Every medicine has some risk of side effects. Doctors take this into account when prescribing medicines. People who abuse these drugs may not understand the risks. The medicines may not be safe for them, especially at higher doses or when taken with other medicines. . NIH: National Institute on Drug Abuse.
An acute hypersensitivity reaction due to exposure to a previously encountered antigen. [HPO:probinson]
An antiquated term indicating arthritis and bone loss.
Generalized seizure that manifests in a form of a brief episode of impairment of consciousness with or without accompanying motor phenomena such as clonic-tonic components, automatisms, or autonomic components.
A coagulation disorder characterized by the partial or complete absence of factor XIII activity in the blood.
Medicinal or recreational utilization of MARIJUANA.
A group of diverse conditions that are characterized by spontaneous, multi-organ autoimmunity, which target both endocrine (adrenal, gonad, pancreatic islet cells, parathyroid, pituitary, thyroid) and non-endocrine (gastrointestinal, integumentary, lymphatic) tissues.
A pyridazine angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. As a prodrug, cilazapril is rapidly metabolized in the liver to cilazaprilat; cilazaprilat competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II, resulting in vasodilation. Cilazaprilat also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow.
A giant cell tumor that arises from the bone and is characterized by the absence of local aggression and lack of metastatic potential.
A response indicating that an individual is confined to bed.
Swelling from fluid accumulation (serous fluid infiltration into the interstitial space) in the cerebellum.
A type of hypothyroidism that results from a defect in the thyroid gland. [HPO:probinson]
Diseases of the DIVERTICULUM often due to infection and/or inflammation (DIVERTICULITIS).
A murine IgG monoclonal Fab' fragment antibody directed against carcinoembryonic antigen (CEA), a protein that is overexpressed by many tumor cell types. For tumors that overexpress CEA, technetium-99m labeled arcitumomab may be used as an adjunct diagnostic imaging tool to obtain prognostic information following resection and to monitor for recurrent disease. (NCI04)
An X-linked recessive syndrome caused by mutation(s) in the GPC3, OFD1, or rarely the GPC4 gene, encoding glypican 3, oral-facial-digital syndrome 1 protein, and glypican 4, respectively. The condition is characterized by macrosomia, coarse facies, cryptorchidism, congenital heart, kidney, liver, spleen, and musculoskeletal abnormalities.
A detrimental reaction to the presence of gluten in food, which may include abdominal pain, fatigue, headaches and paresthesia, or celiac disease.
An electrocardiographic finding of a pattern of right bundle branch block and ST-segment elevation within electrocardiogram leads V1-V3. This pattern emerges as a result of a defect in ion channel genes, resulting in atypical electrophysiological activity in the right ventricle and a propensity for malignant tachyarrhythmias.
A capillary hemangioma that may regress spontaneously. It occurs in infants and children.
A chromosome disorder associated with TRISOMY of all or part of CHROMOSOME 18. Clinical manifestations include INTRAUTERINE GROWTH RETARDATION; CLEFT PALATE; CONGENITAL HEART DEFECTS; MICROCEPHALY; MICROGNATHIA and clenched fists with overlapping fingers. Most affected fetuses do not survive to birth. Those who survive through their first year often have severe INTELLECTUAL DISABILITY.
Decreased activity of coagulation factor XI. Factor XI, also known as plasma thromboplastin antecedent, is a serine proteinase that activates factor IX.
An abnormality of the thyroid gland. [HPO:probinson]
Almost complete absence of subcutaneous and/or visceral adipose tissue.
A small-molecule wortmannin analogue inhibitor of the alpha, gamma, and delta isoforms of phosphoinositide 3-kinase (PI3K) with potential antineoplastic activity. Sonolisib inhibits the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K/Akt signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome is an autosomal dominant disorder characterized by these 4 features, which begin in early childhood and are progressive (summary by Moalem et al., 2015).
A persistent midline depression of the skin over the fat pad of the chin.
A type of focal seizure (i.e., affecting initially only one hemisphere of the brain) that is simple (not resulting in alteration of consciousness) that originates in the occipital lobe. Visual hallucinations are the hallmark of occipital seizures, but are not invariably present. Hallucinations typically commence in the visual field contralateral to the affected visual cortex and then spread to involve the entire visual field. Elementary visual seizures are characterized by fleeting visual manifestations which may be either positive (flashes, phosphenes) or, less commonly, negative (scotoma, hemianopia, amaurosis). Positive phenomena are usually flashes of colour or light, which are simple in shape and may be static or mobile. [PMID:12615636]
Cole-Carpenter syndrome is characterized by bone fragility, craniosynostosis, ocular proptosis, hydrocephalus, and distinctive facial features (Cole and Carpenter, 1987). Genetic Heterogeneity of Cole-Carpenter Syndrome Cole-Carpenter syndrome-2 (CLCRP2; 616294) is caused by mutation in the SEC24D gene (607186).
A prokinetic agent with gastrointestinal (GI) motility-enhancing activity. Although the exact mechanism by which acotiamide exerts its effect has yet to be fully elucidated, this agent appears to inhibit acetylcholinesterase (AchE), an enzyme responsible for the breakdown of acetylcholine (Ach). Increased Ach concentrations lead to an improvement of gastric emptying and GI motility and eventually to a reduction of dyspepsia symptoms.
A rare, non X-linked congenital disorder of glycosylation due to steroid 5 alpha reductase type 3 deficiency with a highly variable phenotype. The disease typically presents with severe visual impairment, variable ocular anomalies (such as optic nerve hypoplasia/atrophy, iris and optic nerve coloboma, congenital cataract, glaucoma), intellectual disability, cerebellar abnormalities, nystagmus, hypotonia, ataxia, and/or ichthyosiform skin lesions. Other reported manifestations include retinitis pigmentosa, kyphosis, congenital heart defects, hypertrichosis and abnormal coagulation. Caused by homozygous or compound heterozygous mutation in the SRD5A3 gene on chromosome 4q12.
A synthetic benzyl styryl sulfone analogue with potential antineoplastic activity. Polo-like kinase 1 inhibitor ON 01910.Na inhibits polo-like kinase1 (Plk1), inducing selective G2/M arrest followed by apoptosis in a variety of tumor cells while causing reversible cell arrest at the G1 and G2 stage without apoptosis in normal cells. This agent may exhibit synergistic antitumor activity in combination with other chemotherapeutic agents. Plk1, named after the polo gene of Drosophila melanogaster, is a serine/threonine protein kinase involved in regulating mitotic spindle function in a non-ATP competitive manner.
A form of congenital disorders of N-linked glycosylation characterised by microcephaly, hepatomegaly, oedema of the extremities, intractable seizures and recurrent infections and increased bleeding tendency. The disease is caused by mutations in the gene ALG13 (Xq23).
A coagulation disorder characterized by the partial or complete absence of factor V activity in the blood.
An orally bioavailable tyrosine kinase inhibitor flumatinib, with potential antineoplastic activity. Upon administration, flumatinib inhibits the wild-type forms of Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and mast/stem cell growth factor receptor (SCFR; c-Kit) and forms of these proteins with certain point mutations. This results in the inhibition of both Bcr-Abl-, PDGFR- and c-Kit-mediated signal transduction pathways, and the proliferation of tumor cells in which these kinases are overexpressed. Bcr-Abl fusion protein is an abnormal, constitutively active enzyme expressed in Philadelphia chromosome positive chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML). PDGFR, upregulated in many tumor cell types, is a receptor tyrosine kinase essential to cell migration and the development of the microvasculature. c-kit, a receptor tyrosine kinase mutated and constitutively activated in certain tumors, plays a key role in tumor cell survival, proliferation, and differentiation.
A subtype of idiopathic generalized epilepsy, whose manifestations occur around puberty, associated with mutation(s) in the EFHC1 gene, encoding EF-hand domain-containing protein 1.
One or more of: deep sclerotic features; hidebound; impaired mobility; ulceration.
Greater than 50% of body surface area involved.
A deletion of the thymine nucleotide at position 5946 of the coding sequence of the BRCA2 gene.
A response indicating that an individual usually uses a bathtub bar.
A change in the nucleotide sequence of the MSH2 gene that is associated with increased risk of disease.
A group of inherited syndromes in which there is impaired growth hormone signaling, despite normal or increased growth hormone concentrations. The syndromes are characterized by some or all of the following: prenatal and/or postnatal growth failure, immature facial features, microcephaly, neurocognitive deficiencies, sensorineural hearing loss, immune dysregulation, and delayed puberty.
A response indicating that an individual usually uses crutches.
A response indicating that an individual needs help from another person for eating.
A cytogenetic abnormality that involves a translocation between chromosomes 2 and 8.
FEV1 is less than or equal to 39 percent and lung symptoms are none to severe.
A response indicating that an individual needs help from another person for getting up.
Compunds that bind to and activate GUANYLYL CYCLASE-C RECEPTORS.
An ependymal tumor that arises from the spinal cord.
A benign neoplasm of the epithelium originating from plasma cells.
Disease with characteristics of intrauterine and postnatal growth retardation, microcephaly, facial dysmorphism, skeletal dysplasia, low-birth weight and brain anomalies. Although microcephalic osteodysplastic primordial dwarfism (MOPD) types 1 and 3 were originally described as two separate entities on the basis of radiological criteria (notably small differences in pelvic and long bone structure), later reports confirmed that the two forms represent different modes of expression of the same syndrome. Although the causative gene remains unknown, homozygosity mapping has allowed identification of a candidate gene region on chromosome 2q (2q14.2-q14.3). Histological studies suggest that MOPD types 1 and 3 result from a basic defect in cell proliferation and tissue differentiation. Transmitted as autosomal recessive trait.
This syndrome has characteristics of congenital and permanent laryngeal abductor paralysis and mental deficiency. It has been described in several families. X-linked inheritance is likely.
A response indicating that an individual is completely able to do something.
A response indicating that an individual usually uses special or built up utensils.
A deletion of the two nucleotides in positions 68 and 69 from the coding sequence of the BRCA1 gene.
A response indicating that an individual needs help from another person for dressing and grooming.
A response indicating that an individual needs help from another person for errands and chores.
A chromosome disorder associated with TRISOMY of all or part of CHROMOSOME 13. Clinical manifestations include CONGENITAL HEART DEFECTS (e.g., PATENT DUCTUS ARTERIOSUS), facial malformations (e.g., CLEFT LIP; CLEFT PALATE; COLOBOMA; MICROPHTHALMIA); HYPOTONIA, digit malformations (e.g., POLYDACTYLY or SYNDACTYLY), and SEIZURES and severe INTELLECTUAL DISABILITY associated with NERVOUS SYSTEM MALFORMATIONS.
BBS21 is an autosomal recessive ciliopathy characterized by obesity, postaxial polydactyly, retinal degeneration, and mild cognitive impairment (Heon et al., 2016; Khan et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of Bardet-Biedl syndrome, see BBS1 (209900).
A finding indicating decreased tissue sensitivity to parathyroid hormone.
A response indicating that an individual usually uses a cane.
An inherited condition caused by mutation(s) in the SLC25A4 gene, encoding ADP/ATP translocase 1. It is characterized by hypertrophic cardiomyopathy.
A response indicating that an individual needs help from another person for reach.
A Chinese herbal medicine (CHM) derived from the root tuber of perennial herbaceous plant Rehmannia glutinosa Libosch (Chinese foxglove root, Radix Rehmanniae Glutinosae) belonging to the Scrophulariaceae family. This traditional Chinese medicine (TCM) is believed to nourish yin and may help relieve any symptoms due to yin deficiency. It may replenish fluids and help with constipation and fever.
A tissue that forms in a location of the body at or in which it is not normally associated.
A response indicating that an individual usually uses a walker.
Disorders of coagulation caused by the depletion of coagulation factors in the peripheral blood.
A molecular genetic abnormality indicating the presence of multiple copies of the FANCE gene.
A molecular genetic abnormality indicating the presence of multiple copies of the FANCD2 gene.
A change in the nucleotide sequence of the POLQ gene.
A rare inherited cancer-predisposing syndrome characterised by the development of a broad spectrum of malignancies during childhood, including mainly brain, haematological and gastrointestinal cancers, although embryonic and other tumours have also been occasionally reported. Non-neoplastic features, in particular manifestations reminiscent of neurofibromatosis type 1 (for example cafe au lait spots, freckling, neurofibromas), as well as premalignant and non-malignant lesions (such as adenomas/polyps) are frequently present before malignancy development.
Presence of lupus anticoagulant (LA) autoantiboides. LA represent a heterogeneous group of autoantibodies, IgG, IgM, or a mixture of both classes, that interfere with standard phospholipid-based coagulant tests (this is only an in vitro phenomenon, LA do not cause reduction of coagulation in vivo). The antibodies are directed against plasma proteins which also bind to phospholipid surfaces.
A response indicating that an individual usually uses a raised toilet seat.
An insertion of a single cytosine nucleotide between positions 5265 and 5266 of the coding sequence of the BRCA1 gene.
Disorders of coagulation caused by autoantibodies generated against native coagulation factors or therapeutically-administered hemostatic agents.
Blood concentration of insulin like growth factor binding protein acid labile subunit level below normal limits. []
A response indicating that an individual usually uses a special or built up chair.
The root of the perennial herbaceous plant Ophiopogon belonging to the Liliaceae family. Mai Dong is believed to tonify yin. This traditional Chinese medicine (TCM) may replenish fluids, moisten the intestines and thereby help relieve constipation. It may also have antipyretic and antitussive effects; it may be used as an expectorant and may moisten the lungs, throat and nose.
The identification of a localized, pathological, or traumatic structural change, damage, deformity, or discontinuity of the bone.
A marked decrease in contrast enhancement that is not due to actual tumor shrinkage, but that may be due to immunotherapy.
A response indicating that an individual usually uses a wheelchair.
A response indicating that an individual needs help from another person for gripping and opening things.
A disorder of platelet function or platelet production that may cause increased bleeding.
A change in the nucleotide sequence of the MLH1 gene that is associated with increased risk of disease.
A nucleotide substitution in the 5' promoter region of the TERT gene at a position that is 146 nucleotides upstream of the translation start site where cytosine has been mutated to thymine.
A nucleotide substitution in the 5' promoter region of the TERT gene at a position that is 124 nucleotides upstream of the translation start site where cytosine has been mutated to thymine.
K ATP channel-associated neonatal diabetes mellitus that does not resolve spontaneously.
A response indicating that an individual usually uses a long-handled appliance for reach.
A response indicating that an individual usually uses a long-handled appliance in the bathroom.
Loss of function mutation(s) in the paternal allele of the GNAS gene, encoding guanine nucleotide-binding protein G(s) subunit alpha isoforms short resulting in dermal ossification beginning in infancy, followed by increasing and extensive heterotopic bone formation in deep muscle and fascia.
A vaccine formulation consisting of rilimogene galvacirepvec (V-PSA-TRICOM; PROSTVAC-V), a recombinant vaccinia virus, and rilimogene glafolivec (F-PSA-TRICOM; PROSTVAC-F), a recombinant fowlpox virus, with potential immunostimulating and antineoplastic activities. Both viruses encode modified forms of human prostate specific antigen (PSA) and the three co-stimulatory molecule transgenes (TRIad of COstimulatory Molecules; TRICOM), B7.1 (CD80), intercellular adhesion molecule-1 (ICAM-1), and lymphocyte function-associated antigen-3 (LFA-3). Using a prime-boost vaccine regimen, with a primary vaccination of rilimogene galvacirepvec followed by multiple booster vaccinations of rilimogene glafolivec, the PSA-TRICOM vaccines infect antigen-presenting cells (APCs), such as dendritic cells (DCs). Upon processing and expression of the PSA and TRICOM proteins on their surfaces, the DCs are able to initiate cytotoxic T-lymphocyte (CTL) responses against PSA-expressing cancer cells. The combination of PSA and TRICOM greatly enhances T-cell activation and T-cell-mediated tumor cell killing.
A lipid-based nanoparticle formulation composed of the apoptosis-inducing sphingolipid ceramide encapsulated within nanoliposomes, with potential apoptotic and antineoplastic activities. Upon administration, ceramide nanoliposomes accumulate in the tumor environment, due to the unique properties of the tumor vasculature, and easily enter tumor cells. This delivers ceramide inside the tumor cells, where ceramide induces apoptosis. Although the process is not completely understood, ceramide-dependent apoptosis most likely results from the downregulation of nutrient transporter proteins, which prevents cellular access to extracellular nutrients and causes tumor cell starvation. This selectively destroys tumor cells. Ceramide alone is insoluble and has a very short half-life; therefore, the nanoliposome formulation increases its solubility and half-life. Ceramide plays a key role in the regulation of autophagy, apoptosis, survival and proliferation. Serving as a tumor suppressor lipid, the expression of ceramide is inversely correlated with tumor cell growth, survival and metastasis.
A variant of sickle cell disease due to homozygosity of the E6V mutation, amino acid substitution of valine for glutamic acid in the sixth position of the beta chain, resulting in the production of hemoglobin S from both alleles.
The ratio of interstitial fluid volume to total body fluid.
A response indicating that an individual is not or was not sexually active.
A coagulation disorder characterized by the partial or complete absence of factor XI activity in the blood.
A molecular abnormality indicating rearrangement of the CRLF2 gene.
Involuntary, fine, continuous, undulating contractions of the eyelid.
An adverse response (dislike) to sound no matter what volume the sound is, characterized by a strong negative reaction to soft sounds that can sometimes be further triggered by seeing the source of the offending sound.
A rare Epstein-Barr virus-positive B-cell lymphoproliferative disorder which presents as an ulcerative mucocutaneous lesion. It is associated with immune suppression, including age-related and drug-induced immunosuppression.
Decreased activity of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 due to inactivating mutation(s) in the HSD11B1 gene. The condition is characterized by hyperandrogenism as a result of increased adrenocorticotropic hormone stimulation of the adrenal gland due to failure of cortisol-mediated down-regulation, and is clinically indistinguishable from H6PD deficiency.
A cytogenetic abnormality characterized by deregulation of genes in 11q.
Decreased or absent activity of the enzyme 17-alpha-hydroxylase/17,20 lyase due to loss-of-function mutation(s) in the CYP17A1 gene. The clinical manifestations of the deficiency are dependent on whether one or both activities of the enzyme are affected, and may include hypertension due to reduced 17-hydroxylase activity and incomplete genital masculinization in 46,XY infants due to reduced 17,20 lyase activity.
An orally bioavailable fluorinated analog of fucose that is a protein fucosylation inhibitor, with potential antineoplastic and immunomodulating activities. Upon administration of SGN-2FF, 2-fluorofucose (2-FF) mimics fucose and is converted to guanosine diphosphate (GDP)-2FF, which prevents the formation of the fucosylation substrate GDP-fucose, and the incorporation of fucose into glycoproteins by fucosyltransferase. As fucosylation of glycoproteins plays a key role in many biological processes, such as protein function, receptor binding, cell signaling and cellular adhesion, and is essential for tumor progression, blocking fucosylation decreases tumor cell growth. In addition, blocking fucosylation of monoclonal antibodies generates fucose-deficient antibodies that exert enhanced antibody-dependent cell-mediated cytotoxicity (ADCC).
A 1000 times reduction in the Philadelphia Chromosome positive cells.
A molecular abnormality indicating rearrangement of the ABL1 gene.
A molecular abnormality indicating rearrangement of the ABL2 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the ALK gene.
A cytogenetic abnormality that refers to any translocation involving the ALK gene.
A change in the nucleotide sequence of the ATR gene.
An orally available inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase, with potential antineoplastic activity. Upon oral administration, ATR kinase inhibitor VX-803 selectively inhibits ATR activity and blocks the downstream phosphorylation of the serine/threonine protein kinase CHK1. This prevents ATR-mediated signaling, which results in the inhibition of DNA damage checkpoint activation, the disruption of DNA damage repair, and the induction of tumor cell apoptosis. ATR, a serine/threonine protein kinase upregulated in a variety of cancer cell types, plays a key role in DNA repair, cell cycle progression and survival; it is activated by DNA damage caused during DNA replication-associated stress.
An orally available inhibitor of the AXL receptor tyrosine kinase (AXL; UFO) and the receptor tyrosine kinase c-Met/hepatocyte growth factor receptor (HGFR) with antineoplastic activity. Upon administration, AXL receptor tyrosine kinase/cMET inhibitor BPI-9016M, binds to both AXL and cMet, thereby disrupting both AXL- and c-Met-mediated signaling pathways. Altogether, this agent inhibits growth in AXL and cMet-overexpressing tumor cells. AXL, a member of the TAM (TYRO3, AXL and MER) family of receptor tyrosine kinases, and cMet, both overexpressed by many tumor cell types, play key roles in tumor cell proliferation, survival, invasion and metastasis.
An acquired coagulation disorder characterized by the partial or complete absence of fibrinogen (factor I) activity in the blood.
An acquired coagulation disorder characterized by the partial or complete absence of tissue factor (factor III) activity in the blood.
An acquired coagulation disorder characterized by the partial or complete absence of factor V activity in the blood.
An acquired coagulation disorder characterized by the partial or complete absence of factor XI activity in the blood.
An acquired coagulation disorder characterized by the partial or complete absence of factor XII activity in the blood.
Hyperthyroidism, the cause of which is not present from birth.
Hypoparathyroidism, the cause of which is not present at birth.
Ovarian failure, the cause of which is not present at birth.
A change in the nucleotide sequence of the ERBB2 gene that that results in constitutive receptor tyrosine-protein kinase erbB-2-dependent signal transduction and activation of downstream signaling pathways.
A change in the nucleotide sequence of the MET gene that that results in constitutive hepatocyte growth factor receptor-dependent signal transduction and activation of downstream signaling pathways.
A change in the nucleotide sequence of the RET gene that results in constitutive proto-oncogene tyrosine-protein kinase receptor Ret-dependent signal transduction and activation of downstream signaling pathways.
Mutation(s) in the TSHR gene resulting in increased function of the thyroid stimulating hormone receptor.
A non-Down syndrome acute megakaryoblastic leukemia that occurs in childhood. It is associated with CBFA2T3-GLIS2 chimeric oncogene and has an unfavorable prognosis.
A non-Down syndrome acute megakaryoblastic leukemia that occurs in childhood. It is associated with t(11;12)(p15;p13) which results in the presence of NUP98-KDM5A chimeric oncogene.
A rare, de novo acute myeloid leukemia in which the blasts harbor BCR-ABL1 translocation in the absence of a history and clinical and laboratory features of chronic myelogenous leukemia.
An acute myeloid leukemia with double mutations of the CEBPA gene.
An acute myeloid leukemia with single mutations of the CEBPA gene.
De novo acute myeloid leukemia with RUNX1 gene mutation, not associated with myelodysplastic syndrome-related cytogenetic abnormalities.
A rare acute myeloid leukemia that occurs in childhood. It is characterized by t(10;11)(p12;q23) which results in MLL-MLLT10 fusion. It is associated with an unfavorable prognosis.
Acute myeloid leukemia with a cytogenetically cryptic fusion of NUP98 to JARID1A, t(11;15)(p15;q35). It typically has a megakaryocytic phenotype and occurs in 10% of pediatric, non-Down syndrome-related acute megakaryoblastic leukemia cases.
Acute myeloid leukemia with often cytogenetically cryptic fusion of NUP98 (chromosome 11p15) with NSD1 (chromosome 5q35). This alteration occurs in 4% of pediatric AML cases.
A rare acute myeloid leukemia that occurs in childhood. It is characterized by t(6;11)(q27;q23) which results in KMT2A-MLLT4 fusion. It is associated with an unfavorable prognosis.
Adenocarcinoma that arises from the ovary of a rat.
A nanoparticle-based formulation containing a recombinant non-replicating adenovirus (Ad) encoding toll-like receptor 5 (TLR5) and its specific ligand protein 502S, with potential antineoplastic and immunomodulating activities. Upon administration, the Ad preferentially and specifically infects cells expressing the Coxsackievirus and adenovirus receptor (CAR), which is highly expressed in certain human tumors, and expresses both TLR5 and a specific agonistic ligand in the same cell. 502S binds to and activates TLR5, thereby allowing for continuous TLR5 signaling. This stimulates dendritic cells (DCs), monocytes, macrophages and the nuclear factor-kappa B (NF-kappaB) signaling cascade. This activation results in the production of pro-inflammatory cytokines, including interferon alpha, tumor necrosis factor-alpha and the interleukins (IL), IL-1 beta, -6 and -12. This may induce a T helper cell-1 (Th1) immune response and activate a cytotoxic T-lymphocyte (CTL) response against tumor associated antigens (TAAs). TLR5, a member of the TLR family, plays a key role in the activation of innate immunity.
An increase of adipocytes in the extracellular space.
Diabetes insipidus complicated by a deficient or absent thirst response to hyperosmolality, usually as a result of hypothalamic damage or dysfunction.
A head and neck carcinoma that has spread extensively to other anatomical sites or is no longer responding to treatment.
A malignant solid neoplasm that has spread to other anatomic sites or is no longer responding to treatment.
A proprietary, albumin-binding platinum (Pt)-based complex containing a prodrug form of the platinum compound cisplatin and a maleimide moiety, with an ability to strongly and selectively bind human serum albumin (HSA), and with potential antineoplastic activity. Upon intravenous administration, the maleimide group of BTP-114 rapidly conjugates with HSA in the bloodstream; this prolongs the blood circulation, enhances the half-life, and alters the biodistribution of BTP-114, as compared to cisplatin alone. Thus, BTP-114 demonstrates enhanced extravasation to the tumor, an increased accumulation in the tumor tissue and enhanced uptake by cancer cells. The prodrug form is reduced in the hypoxic tumor cell environment, which releases the highly cytotoxic active metabolite cisplatin. Once inside the tumor cell, cisplatin binds to nucleophilic groups, such as GC-rich sites, in DNA and induces intrastrand and interstrand DNA cross-links, resulting in apoptosis and cell growth inhibition. Compared to cisplatin alone, BTP-114 has improved selectivity towards tumor tissue, thereby enhancing efficacy while reducing systemic toxicities.
A response indicating agreement at almost all times.
A response indicating disagreement at almost all times.
A response indicating agreement at all times.
A response indicating disagreement at all times.
An unusual variant of capillary hemangioma. It is characterized by a unique anastomosing sinusoidal-like architecture which may mimic angiosarcoma. It was originally described in the kidney but rare cases have been reported in other sites.
An orally bioavailable androgen receptor (AR) antagonist, with potential antineoplastic activity. Upon oral administration, AR antagonist TRC253 specifically binds to both wild-type and certain mutant forms of AR, thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot translocate to the nucleus. This prevents binding to and transcription of AR-responsive genes, inhibits the expression of genes that regulate prostate cancer cell proliferation, and may lead to an inhibition of growth of tumor cells in which AR is overexpressed and/or mutated. AR is often overexpressed and/or mutated in prostate cancers and plays a key role in proliferation, survival and chemoresistance of tumor cells.
Anemia that results from a decreased rate of erythropoiesis.
Any form of anemia that results from the absence of, or the defective action of, any enzyme involved in erythropoiesis.
Anemia that results from an increased rate of erythrocyte destruction.
An antibody-drug conjugate (ADC), consisting of a human monoclonal antibody directed against AXL receptor tyrosine kinase (AXL; UFO) and conjugated, through a protease-cleavable linker, to the cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of HuMax-AXL-ADC binds to AXL, which is expressed on the surfaces of a variety of cancer cell types. Upon endocytosis and enzymatic cleavage, MMAE is released into the tumor cell cytosol, where it binds to tubulin and inhibits tubulin polymerization; this may result in G2/M phase arrest and apoptosis. AXL, a member of the TAM (TYRO3, AXL and MER) family of receptor tyrosine kinases and overexpressed by many tumor cell types, plays a key role in tumor cell proliferation, survival, invasion and metastasis; its expression is associated with drug resistance and poor prognosis.
A bispecific, Fc domain-containing, monoclonal antibody with potential antineoplastic activity. Anti-CD20/CD3 monoclonal antibody XmAb13676 contains two antigen-recognition sites: one for human CD3, a T cell surface antigen, and one for human CD20, a tumor-associated antigen (TAA) that is exclusively expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell malignancies. Upon administration, XmAb13676 binds to both T-cells and CD20-expressing B-lineage tumor cells. The resulting cross-linkage may trigger a potent cytotoxic T-lymphocyte (CTL) response against the CD20-expressing tumor B-cells. Inclusion of an Fc domain on the antibody prolongs the half-life of the bispecific antibody and enhances T-cell-mediated tumor cell killing because the agent is able to bind to Fc receptors.
An antibody-drug conjugate (ADC) consisting of an engineered cysteine humanized monoclonal antibody (EC-mAb) targeting CD352 (SLAM family member 6; SLAM6) that is conjugated to the cytotoxic, DNA minor-groove crosslinking agent pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon administration of anti-CD352 ADC SGN-CD352A, the antibody moiety targets the cell surface antigen CD352. Upon antibody/antigen binding, internalization, and lysosome uptake, the cytotoxic PBD moiety is released. In turn, the imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces DNA strand breaks, inhibits DNA replication, leads to G2/M cell cycle arrest, induces cell death, and inhibits the proliferation of CD352-overexpressing tumor cells. CD352, a tumor-associated antigen (TAA), is overexpressed on a variety of cancers. Cysteine engineering of the monoclonal antibody allows for a site-specific, stable conjugation and uniform loading of the PBD agent to the antibody.
A bispecific monoclonal antibody composed of a binding domain for an epitope found on the cell-surface receptor CD40 linked to a binding domain directed to an as of yet undisclosed tumor-associated antigen (TAA), with potential immunomodulating and antineoplastic activities. Upon administration of anti-CD40/anti-TAA bispecific monoclonal antibody ABBV-428, the anti-TAA moiety targets and binds to the TAA expressed on the tumor cells. The agonistic anti-CD40 moiety targets and binds to various CD40-expressing immune cells. This leads to the activation and proliferation of effector and memory T-cells, and enhances the immune response against tumor cells, which kills and inhibits the proliferation of the TAA-expressing tumor cells. CD40, a stimulatory receptor and a member of the tumor necrosis factor receptor superfamily (TNFRSF), is expressed on various immune cells, such as macrophages, B-lymphocytes, and dendritic cells (DCs); it plays a key role in the activation of the immune system.
A monoclonal antibody targeting the ectoenzyme 5'-ecto-nucleotidase (cluster of differentiation 73; CD73; 5'-NT; ecto-5'-nucleotidase; NT5E), with potential immunomodulating and antineoplastic activities. Upon administration, anti-CD73 monoclonal antibody BMS-986179 targets and binds to CD73, leading to clustering and internalization of CD73. This prevents CD73-mediated conversion of extracellular adenosine monophosphate (AMP) to adenosine and decreases the amount of free adenosine. This prevents adenosine-mediated suppression of lymphocyte activity and increases the activity of CD8-positive effector cells. This also activates macrophages, and reduces the activity of both myeloid-derived suppressor cells (MDSCs) and regulatory T-lymphocytes. By abrogating the inhibitory effect on the immune system and enhancing the cytotoxic T-cell-mediated immune response against cancer cells, tumor cell growth is decreased. CD73, a plasma membrane protein belonging to the 5'-nucleotidase (NTase) family, is upregulated on a number of cancer cell types and catalyzes the conversion of extracellular nucleotides, such as AMP, to membrane-permeable nucleosides, such as adenosine; it plays a key role in adenosine-mediated immunosuppression within the tumor microenvironment.
An immunoconjugate consisting of a human monoclonal antibody directed against the tumor-associated antigen (TAA) cadherin-6 (CDH6; CDH-6) conjugated to a maytansine-based cytotoxic agent, with potential antineoplastic activity. The monoclonal antibody moiety of HKT288 targets and binds to CDH6 located on tumor cell surfaces. After internalization, the maytansine moiety binds to tubulin, which disrupts microtubule assembly/disassembly dynamics and inhibits both division and proliferation of CDH6-expressing tumor cells. CDH6, a member of the cadherin family and overexpressed by a variety of cancers, plays a key role in tumor cell proliferation.
A humanized immunoglobulin (Ig) G2 monoclonal antibody (mAb) directed against the cytokine colony stimulating factor 1 (CSF1; CSF-1; macrophage colony-stimulating factor; M-CSF), with potential immunomodulating and antineoplastic activities. Upon administration, anti-CSF1 monoclonal antibody PD-0360324 targets, binds to and neutralizes CSF1. This prevents the binding of CSF1 to its receptor CSF1R (CD115; M-CSFR), which is expressed on various immune cells, such as monocytes and macrophages. This prevents CSF1R activation and CSF1R-mediated signaling in these cells; this inhibits monocyte differentiation, blocks the activity of macrophages, and reduces their production of inflammatory mediators, which reduces inflammation. By blocking the activity and proliferation of CSF1R-dependent tumor-associated macrophages (TAMs) in the tumor microenvironment, PD-0360324 reduces TAM-mediated immune suppression, decreases regulatory T-cells (Tregs), re-activates the immune system, and improves anti-tumor cell responses mediated by increasing infiltration by cytotoxic T-cells. TAMs play key roles in immune suppression, and tumor cell proliferation and survival. CSF-1 plays a key role in the regulation of the proliferation, differentiation and survival of monocytes and macrophages.
A humanized immunoglobulin (Ig) G1 monoclonal antibody (mAb) against C-X-C chemokine receptor type 4 (CXCR4), with potential antineoplastic activity. Upon administration, anti-CXCR4 mAb PF-06747143 binds to CXCR4, thereby preventing the binding of stromal cell-derived factor-1 (SDF-1 or CXCL12) to CXCR4 and inhibiting CXCR4 activation. This results in decreased proliferation and migration of CXCR4-expressing tumor cells. In addition, PF-06747143 promotes cell death through the induction of both complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) family, is upregulated in several tumor cell types and plays an important role in cancer cell proliferation, survival, and chemotaxis, and in tumor angiogenesis.
An antibody mixture composed of six humanized, immunoglobulin G1 (IgG1) monoclonal antibodies directed against three members of the human epidermal growth factor receptor (EGFR; HER) family: EGFR (HER1; ErbB1), HER2 (ErbB2) and HER3 (ErbB3), with potential antineoplastic activity. Upon administration of anti-EGFR/HER2/HER3 monoclonal antibody mixture Sym013, the six antibodies bind to non-overlapping epitopes on EGFR, HER2 and HER3, which prevents both ligand binding and receptor activation, and induce simultaneous down-modulation of EGFR, HER2 and HER3. This inhibits the activation of HER-dependent signaling pathways and HER-dependent tumor cell proliferation. Overexpression of the HER family plays a key role in many cancers; targeting multiple HER family members simultaneously may increase therapeutic efficacy.
A recombinant fusion protein comprised of a human monoclonal antibody directed against fibroblast activation protein-alpha (FAP) linked to an engineered, variant form of interleukin-2 (IL-2v), with potential immunostimulating and antineoplastic activities. Upon administration of RO6874281, the monoclonal antibody moiety recognizes and binds to FAP, thereby concentrating IL-2 in FAP-expressing tumor tissue. Subsequently, the IL-2 moiety of this fusion protein may stimulate a local immune response and activate natural killer (NK) cells and cytotoxic T-cells. FAP is a cell surface protein that is expressed on a wide variety of cancer cells. IL-2v cannot bind to IL-2 receptor-alpha (CD25, IL2Ra) and does not activate regulatory T-cells (Tregs).
An antibody-drug conjugate (ADC) composed of a human monoclonal antibody directed against the extracellular domain of receptor-type tyrosine-protein kinase FLT3 (FLT-3; FMS-like tyrosine kinase 3; CD135; fetal-liver kinase 2; FLK2) and conjugated, via an oxime linker and the site-directed non-natural amino acid linker para-acetyl-phenylalanine (pAcF), to a microtubule-disrupting cytotoxic agent, with potential antineoplastic activity. Upon administration of ADC AGS62P1, the antibody moiety targets and binds to FLT3. Upon antibody/antigen binding and internalization, the microtubule-targeting agent binds to and inhibits tubulin polymerization, which results in G2/M phase arrest and tumor cell apoptosis. The site-specific conjugation of the cytotoxic agent to the antibody, through pAcF, improves the biophysical properties of AGS62P1, increases payload distribution and stability, and optimizes its efficacy. FLT3, a class III tyrosine kinase receptor, is overexpressed or mutated in most B lineage, acute lymphoblastic leukemias and acute myeloid leukemias.
An anti-human glucocorticoid-induced tumor necrosis factor receptor (GITR; tumor necrosis factor superfamily member 18; TNFRSF18; CD357) agonistic monoclonal antibody, with potential immune checkpoint modulating activity. Anti-GITR antibody BMS-986156 binds to and activates GITR, which is expressed on the cell surface of multiple types of T-cells. This stimulates the immune system, induces both the activation and proliferation of tumor antigen-specific T-effector cells (Teffs), and suppresses the function of activated T-regulatory cells (Tregs). This leads to tumor cell eradication. GITR, a member of the TNF receptor superfamily and T-cell receptor co-stimulator, is expressed on the surface of multiple immune cell types, including Tregs, Teffs, B-cells, and natural killer (NK) cells. Inappropriately activated Tregs suppress both Teffs and T-cell receptor (TCR) signaling.
An anti-glypican 3 (GPC3; GPC-3)/anti-CD3 bispecific monoclonal antibody, with potential immunostimulating and antineoplastic activities. Anti-GPC3/CD3 bispecific antibody ERY974 possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for GPC3, a tumor-associated antigen (TAA) overexpressed on the surface of certain tumor cells. Upon administration of ERY974, this bispecific antibody simultaneously binds to both CD3-expressing and GPC3-expressing cells, thereby crosslinking GPC3-expressing tumor cells and cytotoxic T-lymphocytes (CTLs). This may result in potent CTL-mediated lysis of GPC3-expressing tumor cells. GPC3, a heparan sulfate proteoglycan and an oncofetal antigen protein, is overexpressed in a variety of cancers; it plays a role in cell division and growth regulation.
A human immunoglobulin (Ig) G1 kappa monoclonal antibody (mAb) targeting a unique epitope in the stalk of the influenza A hemagglutinin (HA) protein, with broad influenza A virus neutralization activity. MEDI8852 was derived from an antibody isolated from human memory B-cells from patients previously infected with influenza caused by type A strains that was further optimized to increase neutralization potential. Upon infusion, MEDI8852 targets and binds to a region within the stalk of the HA protein that is highly conserved amongst all influenza A virus subtypes. This neutralizes and prevents essential steps of the viral lifecycle, thereby blocking infectivity of all influenza A virus subtypes. HA, a glycoprotein found on the surface of the influenza virus, plays a key role in viral attachment and cell entry.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (EGFR2; HER2) and conjugated to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon administration of anti-HER2 ADC RC48, the antibody moiety targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, the cytotoxic agent induces tumor cell apoptosis, through an as of yet not publicly known mechanism. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types.
An antibody-drug conjugate (ADC) composed of HT-19, a monoclonal antibody directed against the human epidermal growth factor receptor 2 (ERBB2; HER2), conjugated, via a proprietary biodegradable, hydrophilic polymer backbone and various linkers, to proprietary auristatin-derived payload molecules (about 15 per antibody), with potential antineoplastic activity. Upon administration of anti-HER2/auristatin payload ADC XMT-1522, the antibody moiety targets and binds to a unique epitope in the extracellular domain (ECD) of HER2. Upon internalization, cleavage and release of the cytotoxic molecules, the auristatin-derived molecules bind to tubulin and inhibit its polymerization, which results in G2/M phase arrest and induces apoptosis of HER2-expressing tumor cells. The attachment of multiple auristatin molecules to the backbone enables XMT-1522 to effectively kill tumors that express relatively low amounts of the HER2 protein; therefore, this agent shows increased therapeutic potential in tumors with low HER2 expression compared to other anti-HER2 antibody-based therapies. The polymer-based proprietary platform optimizes delivery of the cytotoxic drug payload and improves drug solubility.
An agonistic humanized monoclonal antibody that recognizes inducible T-cell co-stimulator (ICOS; CD278), with potential antineoplastic activity. Upon administration, anti-ICOS agonist monoclonal antibody JTX-2011 targets and binds to ICOS expressed on certain T-cells. This stimulates ICOS-mediated signaling, induces proliferation of ICOS-positive T-cells, enhances cytotoxic T-lymphocyte (CTL) survival and augments the CTL-mediated immune response against tumor cells. ICOS, a T-cell specific, CD28-superfamily co-stimulatory molecule and immune checkpoint protein, is normally expressed on certain activated T-cells and plays a key role in the proliferation and activation of T-cells.
A monoclonal antibody directed against programmed cell death-1 ligand 1 (PD-L1), with immune checkpoint inhibitory and potential antineoplastic activities. Upon administration, anti-PD-L1 monoclonal antibody FAZ053 binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1), which may enhance the T-cell-mediated anti-tumor immune response and reverse T-cell inactivation. PD-L1 is overexpressed by many human cancer cell types. PD-L1 binding to PD-1 on T-cells suppresses the immune system and results in immune evasion. PD-1, a transmembrane protein expressed on activated T-cells, is a negative regulator of the immune system that limits the expansion and survival of CD8+ T-cells.
An injectable formulation of a monoclonal antibody directed against programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), with immune checkpoint inhibitory and potential antineoplastic activities. Upon subcutaneous administration, anti-PD-L1 monoclonal antibody KN035 binds to PD-L1, blocking its binding to and activation of its receptor programmed death 1 (PD-1), which may enhance the T-cell-mediated immune response to neoplasms and reverse T-cell inactivation. PD-L1 is overexpressed by many human cancer cell types. PD-L1 binding to PD-1 on T-cells suppresses the immune system and results in immune evasion. PD-1, a transmembrane protein expressed on activated T-cells, is a negative regulator of the immune system that limits the expansion and survival of CD8+ T cells.
A monoclonal antibody directed against human transforming growth factor beta (TGF-beta), with potential antineoplastic activity. Anti-TGF-beta monoclonal antibody NIS793 specifically targets and binds to TGF-beta, thereby preventing the activation of TGF-beta-mediated signaling pathways. TGF-beta, a pro-inflammatory mediator that is mutated and/or overexpressed in a number of cancer cell types, is involved in cancer cell proliferation and migration, and tumor progression.
An agonistic anti-human glucocorticoid-induced tumor necrosis factor receptor (tumor necrosis factor receptor superfamily, member 18; TNFRSF18; GITR; CD357) humanized monoclonal antibody, with potential immune checkpoint modulating activity. Anti-human GITR monoclonal antibody AMG 228 binds to and activates GITRs found on multiple types of T-cells. This stimulates the immune system, induces both the activation and proliferation of tumor-antigen-specific T effector cells (Teffs), and suppresses the function of activated T regulatory cells (Tregs). This leads to immune-mediated tumor cell eradication though a cytotoxic T-lymphocyte (CTL) response. GITR, a member of the TNF receptor superfamily and T-cell receptor co-stimulator, is expressed on the surface of multiple immune cell types, including Tregs, Teffs, B-cells, and natural killer (NK) cells. Inappropriately activated Tregs suppress Teffs and suppress T-cell receptor (TCR) signaling.
A water-based proprietary mouthwash with anti-inflammatory, antimicrobial and analgesic activities. Upon rinsing with this mouthwash, the unspecified ingredients may help prevent or reduce the symptoms and severity of mucositis.
A monoclonal antibody-drug conjugate (ADC) comprised of human immunoglobulin G1 (IgG1) clone CR014, which targets the extracellular domain of T-cell immunoglobulin mucin-1 (TIM-1; HAVCR1), that is linked, via a valine-citrulline (VC) peptide linker, to the potent cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration of ADC anti-TIM-1-vcMMAE CDX-014, the monoclonal antibody moiety targets and binds to TIM-1. Upon internalization and proteolytic cleavage, MMAE is released into the cytosol of TIM-1-expressing tumor cells, binds to tubulin, and inhibits microtubule polymerization, which induces both G2/M phase arrest and tumor cell apoptosis. TIM-1 is upregulated in a variety of cancer cell types while only minimally expressed in healthy tissue. The linkage system in CDX-014 is highly stable in plasma, resulting in increased specificity and cytotoxic efficacy towards TIM-1-positive cells.
A human, soluble fusion protein consisting of the extracellular domain of the CD95 receptor fused to the Fc-domain of the human IgG antibody, with potential antineoplastic activity. Upon administration, antibody-like CD95 receptor/Fc-fusion protein CAN-008 binds to the CD95 ligand (CD95L) and blocks the binding of CD95L to the CD95 receptor. In tumor cells, blockage of CD95L-mediated signaling pathways may prevent cell migration and invasive cell growth; in healthy cells, blockage of CD95L-mediated signaling pathways may prevent apoptosis and may protect cell damage. Activation of the CD95 receptor plays an important role in the initiation of apoptosis in healthy cells or the invasive growth of cancer cells.
Any agent that has a biological nature, such as agents containing living organisms, derived from living organisms, or comprised of ex vivo synthesized analogs of substances derived from living organisms, and that exerts antineoplastic activity.
Any agent that specifically inhibits a particular enzyme that is overexpressed and/or mutated in cancer cell pathways. Antineoplastic enzyme inhibitors specifically target tumor cells by targeting enzymes that are not normally expressed or are minimally expressed in normal, healthy tissues.
Any agent that inhibits the activity of any protein that is involved in cancer-specific pathways. An antineoplastic protein inhibitor is a specific cancer cell-targeting agent.
A small molecule and androgen receptor (AR) antagonist with potential antineoplastic activity. Apalutamide binds to AR in target tissues thereby preventing androgen-induced receptor activation and facilitating the formation of inactive complexes that cannot be translocated to the nucleus. This prevents binding to and transcription of AR-responsive genes. This ultimately inhibits the expression of genes that regulate prostate cancer cell proliferation and may lead to an inhibition of cell growth in AR-expressing tumor cells.
Any agent that directly targets the apoptotic pathway and has an antineoplastic effect.
A spray formulation containing a saliva substitute, composed of potassium chloride, sodium chloride, magnesium chloride, calcium chloride, dipotassium phosphate and monopotassium phosphate, that has potential anti-xerostomia activity. Upon direct oral application of the artificial saliva spray, a protective film of moisture is deposited over the mucous membranes of the mouth, which relieves dryness of the mucous membranes and increases salivary flow. In addition, artificial saliva may help prevent chemotherapy- or radiotherapy-induced oral mucositis.
A usually aggressive and invasive pituitary gland adenoma characterized by excessive p53 immunoreactivity, increased mitotic activity, and MIB-1 proliferative index greater than 3%.
A cyst arising from an ovarian follicle that produces hormones independent of gonadotropin stimulation.
Idiopathic infantile hypercalcemia is a condition characterized by high levels of calcium in the blood (hypercalcemia). Two types of idiopathic infantile hypercalcemia have been identified and are distinguished by their genetic causes: infantile hypercalcemia 1 and infantile hypercalcemia 2. In infants with either type, hypercalcemia can cause vomiting, increased urine production (polyuria), dehydration, constipation, poor feeding, weight loss, and an inability to grow and gain weight as expected (failure to thrive). As they age, affected babies usually have delayed development of mental and movement abilities (psychomotor delay). Individuals with infantile hypercalcemia 1 or 2 may also have high levels of calcium in their urine (hypercalciuria) and deposits of calcium in their kidneys (nephrocalcinosis).With treatment, the outward symptoms of hypercalcemia, such as vomiting, dehydration, failure to thrive, and psychomotor delay, usually improve in childhood. However, affected children still tend to have higher-than-normal amounts of calcium in their blood and urine and calcium deposits in their kidneys. By adulthood, long-term hypercalcemia and hypercalciuria can lead to the formation of kidney stones (nephrolithiasis) and may damage the kidneys and impair their function. Affected adults may also develop calcium deposits in the joints or in the clear outer covering of the eye (the cornea), and some have low bone mineral density (osteoporosis).In rare cases, affected individuals do not have symptoms of hypercalcemia in infancy, and the condition begins in later childhood or adulthood. These individuals usually develop hypercalciuria, nephrocalcinosis, and nephrolithiasis, although the features may not cause any obvious health problems.Although most signs and symptoms are similar between the two known types of idiopathic infantile hypercalcemia, individuals with infantile hypercalcemia 2 have low levels of a mineral called phosphate in the blood (hypophosphatemia), while phosphate levels are typically normal in people with infantile hypercalcemia 1.
B acute lymphoblastic leukemia characterized by amplification of a portion of chromosome 21. It usually occurs in children and is associated with an adverse prognosis.
B acute lymphoblastic leukemia with translocations involving tyrosine kinases, or translocations involving either the cytokine receptor-like factor 2 (CRLF2) or rearrangements leading to truncation and activation of the erythropoietin receptor (EPOR). It is associated with an adverse prognosis.
B lymphoblastic leukemia/lymphoma with translocations involving tyrosine kinases, or translocations involving either the cytokine receptor-like factor 2 (CRLF2) or rearrangements leading to truncation and activation of the erythropoietin receptor (EPOR). It is associated with an adverse prognosis.
B lymphoblastic leukemia/lymphoma characterized by amplification of a portion of chromosome 21. It usually occurs in children and is associated with an adverse prognosis.
A change in the nucleotide sequence of the BARD1 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the BCL2 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the BCL6 gene.
A complex mutation in the BLM gene consisting of a 6 base pair deletion of the nucleotide sequence ATCTGA encompassing nucleic acid positions 2207 through 2212 accompanied by an insertion of 7 base pairs with the sequence TAGATTC.
A variation in the amino acid sequence for Bloom syndrome protein.
A change in the amino acid sequence of breast cancer type 1 susceptibility protein where a deletion mutation results in the replacement of the glutamic acid at position 23 with a valine immediately followed by a stop codon.
A change in the amino acid sequence of breast cancer type 1 susceptibility protein where an insertion mutation results in the replacement of the glutamine at position 1756 with a proline immediately followed by a stop codon.
A variation in the amino acid sequence for breast cancer type 1 susceptibility protein.
A change in the amino acid sequence of breast cancer type 2 susceptibility protein where a deletion mutation results in the replacement of the serine at position 1982 with an arginine immediately followed by a stop codon.
A variation in the amino acid sequence for breast cancer type 2 susceptibility protein.
A change in the nucleotide sequence of the BRIP1 gene.
A change in the nucleotide sequence of the BTK gene.
An orally available inhibitor of Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon administration, DTRMWXHS-12 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B-cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes.
An orally bioavailable, selective inhibitor of Bruton's tyrosine kinase (BTK), with potential antineoplastic activity. Upon administration, M7583 targets and covalently binds to BTK, thereby preventing its activity. This leads to an inhibition of B cell receptor (BCR) signaling and inhibits cell proliferation of B-cell malignancies. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
A stable, nanovesicle formulation composed of a synthetic form of the human glycoprotein saposin C (SapC) linked to the phospholipid dioleoylphosphatidylserine (DOPS), with potential antineoplastic activity. Upon intravenous administration, the BXQ-350 nanovesicle formulation selectively targets and preferentially accumulates in tumor vessels and cells, due to the leaky nature of tumor vasculature and the presence of phosphatidylserine (PS) lipids in tumor cell membranes. Upon binding to the phospholipids in the tumor cell membrane, SapC fuses with the membrane and is internalized leading to its accumulation within the internal membrane. SapC becomes active in the acidic tumor microenvironment and as a lysosomal sphingolipid activator protein, activates lysosomal enzymes, such as beta-glucosidase, acid sphingomyelinase, and beta-galactosylceramidase. This leads to the degradation of glucosylceramide and sphingomyelin, and the conversion of galactosylceramide to ceramide, respectively. This elevates intracellular ceramide levels, activates caspases and induces ceramide-mediated apoptosis, which together lead to an inhibition of tumor cell growth. SapC plays key roles in lipid transport and organization of biological membranes and has strong lipid membrane binding activity.
A response indicating that an individual usually uses a bathtub seat.
An orally bioavailable, Bcr-Abl tyrosine kinase inhibitor (TKI), with potential antineoplastic activity. Upon administration, Bcr-Abl kinase inhibitor K0706 selectively targets and binds to the Bcr-Abl fusion oncoprotein, including various Bcr-Abl mutant forms, such as those with the 'gatekeeper' resistance mutation T315I. This inhibits proliferation of Bcr-Abl-expressing tumor cells. The Bcr-Abl fusion protein is an aberrantly activated tyrosine kinase produced by certain leukemia cells. T315I, an amino acid substitution where threonine (T) has been mutated to isoleucine (I) at position 315 in the tyrosine-protein kinase ABL1 portion of the Bcr-Abl fusion protein, plays a key role in resistance to certain chemotherapeutic agents and its expression is associated with poor prognosis.
A mutation that occurs on both alleles of a single gene.
An orally bioavailable, probiotic supplement containing the non-pathogenic microorganisms Bifidobacterium animalis and Lactobacillus rhamnosus subspecies lactis with potential immunomodulating, anti-diarrheal and mucosal protective activities. Upon oral ingestion, the naturally-occurring bacterial components in Bifidobacterium animalis/Lactobacillus rhamnosus subspecies lactis probiotic supplement may improve digestion and help to maintain adequate colonization of the gastrointestinal (GI) tract by modulating the composition of the normal microflora. They produce lactic acid, hydrogen peroxide and other substances during fermentation, thereby creating an acidic environment that is unfavorable for pathogens. During colonization in the GI tract, the bacteria may also form a protective intestinal barrier, which may prevent damage to the mucosal epithelium, maintains the integrity of the epithelial barrier from potential damage by toxins and certain chemicals, and reduces the potential for attachment of pathogens. This further protects against bacterial translocation and infection. In addition, this agent may reduce the secretion of pro-inflammatory cytokines and may potentiate natural and acquired immunity. Altogether, this may increase immunity, prevent GI mucosal damage, malabsorption, inflammation, and reduce diarrhea, such as diarrhea induced by inflammation and GI mucosa-damaging agents.
An indication that a sample block has been depleted by testing.
An assessment of the bone response of a disease to a therapy.
A botanical-based formulation derived from the Taiwanese mushroom Antrodia cinnamomea, with potential antineoplastic activity, Upon administration, the components in LEAC-102 may exert cytotoxic effects against cancer cells.
A congenital metabolic disorder characterized by a deficiency in the enzyme uroporphyrinogen III synthase, which occurs in cattle.
A congenital metabolic disorder characterized by a deficiency in the enzyme ferrochelatase, which occurs in cattle.
The hydrobromide salt form of burixafor, an orally bioavailable inhibitor of CXC chemokine receptor 4 (CXCR4) with hematopoietic stem cell (HSC)-mobilization and chemosensitizing activities. Upon administration, burixafor binds to the chemokine receptor CXCR4, thereby preventing the binding of stromal cell-derived factor-1 (SDF-1 or CXCL12) to the CXCR4 receptor and subsequent receptor activation. This may induce the mobilization of hematopoietic stem and progenitor cells from the bone marrow into the peripheral circulation. Additionally, burixafor-mediated mobilization of disseminated tumor cells (DTCs) from the bone marrow into the blood may make these metastatic tumor cells more susceptible to the actions of chemotherapeutic agents. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) gene family, plays an important role in chemotaxis and angiogenesis and is upregulated in several tumor cell types. CXCL12/CXCR4 interaction induces retention of hematopoietic cells in the bone marrow.
A molecular genetic abnormality indicating the presence of a deletion mutation in exon 9 of the CALR gene. These deletion mutations are associated with primary myelofibrosis and may be predicative of a favorable survival prognosis.
A molecular genetic abnormality indicating the presence of an insertion mutation in exon 9 of the CALR gene. These insertion mutations are associated with primary myelofibrosis and may be predicative of shortened survival.
A molecular genetic abnormality indicating the presence of a mutation in exon 9 of the CALR gene.
A deletion of 52 nucleotides from the coding sequence of the CALR gene from positions 1092 through 1143.
An insertion of five nucleotides, TTGTC, between positions 1154 and 1155 of the coding sequence of the CALR gene.
A change in the amino acid composition of the calreticulin protein where a frameshift mutation results in the insertion of 47 non-canonic amino acids followed by a stop codon immediately after the lysine residue at position 385.
A change in the amino acid composition of the calreticulin protein where a frameshift mutation results in the insertion of 46 non-canonic amino acids followed by a stop codon immediately after the leucine residue at position 367.
A variation in the amino acid sequence for the calreticulin protein.
A molecular genetic abnormality indicating the presence of multiple copies of the CCND2 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the CCND3 gene.
A therapeutic peptide vaccine containing the human telomerase reverse transcriptase catalytic subunit (hTERT)-derived universal cancer peptides 2 (UCP2) and 4 (UCP4), and combined with the immunoadjuvant Montanide ISA 51 VG, with potential immunostimulating and antineoplastic activities. Vaccination with the CD4-specific telomerase peptide vaccine UCPVax activates the immune system to mount a T-helper 1 (TH1) CD4-positive T-lymphocyte immune response against and ultimately killing telomerase-expressing cells. Telomerase, a reverse transcriptase normally repressed in healthy cells, is overexpressed in most cancer cells and plays a key role in cellular proliferation.
A variant of signal regulatory protein alpha (SIRPa) that antagonizes the human cell surface antigen CD47, with potential phagocytosis-inducing, immunostimulating and antineoplastic activities. Upon administration, ALX148 binds to CD47 expressed on tumor cells and prevents the interaction of CD47 with its ligand SIRPa, a protein expressed on phagocytic cells. This prevents CD47/SIRPa-mediated signaling and abrogates the CD47/SIRPa-mediated inhibition of phagocytosis. This induces pro-phagocytic signaling mediated by the binding of the pro-phagocytic signal calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages. This results in macrophage activation and the specific phagocytosis of tumor cells. In addition, blocking CD47 signaling activates both an anti-tumor cytotoxic T-lymphocyte (CTL) immune response and T cell-mediated killing of CD47-expressing tumor cells. CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate.
A change in the nucleotide sequence of the CDK12 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the CDK4 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the CDK6 gene.
A cancer prime/boost vaccine-based immunotherapeutic consisting of a prime, which is comprised of a proprietary version of the recombinant vaccinia viral vector, modified vaccinia Ankara-Bavarian Nordic (MVA-BN) and a recombinant fowlpox viral vector, used for the boosts, encoding both the two tumor-associated antigens (TAA), carcinoembryonic antigen (CEA) and mucin-1 (MUC-1), and TRICOM, which is comprised of three immune-enhancing co-stimulatory molecules, B7-1, ICAM-1 and LFA-3, with potential immunostimulatory and antineoplastic activities. The administration of the vaccinia priming dose is followed by multiple boosting doses of the fowlpox vector. CEA-MUC-1-TRICOM Vaccine CV301 may enhance presentation of CEA and MUC-1 to antigen-presenting cells (APCs) and may activate a cytotoxic T-lymphocyte (CTL) response against CEA- and MUC-1-expressing tumor cells. In addition, CV301 upregulates the expression of PD-L1 due to CTL-mediated tumor attack; additionally, when combined with a PD-1 immune checkpoint inhibitor, the antitumor effect may be increased. CEA and MUC-1 are overexpressed in certain cancers.
A change in the nucleotide sequence of the CREBBP gene.
An inhibitor of colony stimulating factor 1 receptor (CSF1R; CSF-1R), with potential antineoplastic activity. Upon administration, CSF1R inhibitor PLX73086 targets and binds to CSF1R, thereby blocking CSF1R activation and CSF1R-mediated signaling. This inhibits the activity of tumor-associated macrophages (TAMs) in the tumor tissue and prevents TAM-related tumor cell growth. CSF1R, also known as macrophage colony-stimulating factor receptor (M-CSFR) and CD115 (cluster of differentiation 115), is a cell-surface receptor for its ligand colony stimulating factor 1 (CSF1) and plays major roles in tumor cell proliferation and metastasis.
An orally bioavailable inhibitor of C-X-C chemokine receptor type 4 (CXCR4), with potential antineoplastic activity. Upon administration, USL311 binds to CXCR4, thereby preventing the binding of stromal-cell derived factor-1 (SDF-1 or CXCL12) to CXCR4 and inhibiting CXCR4 activation, which may result in decreased proliferation and migration of CXCR4-expressing tumor cells. CXCR4, a chemokine receptor belonging to the G protein-coupled receptor (GPCR) family, plays an important role in chemotaxis and angiogenesis, and is upregulated in several tumor cell types.
Rickets due to low calcium concentrations, the cause of which can be nutritional or genetic.
Oral squamous cell carcinoma that occurs in a dog.
Adeonocarcinoma of the thyroid gland occuring in a dog.
A radiopharmaceutical tracer containing the anti-diabetic agent metformin, a biguanide and hydrophilic organic cation, and labeled with carbon 11 (11C), used to measure metformin uptake by cancer cells using positron emission tomography (PET). Upon administration of carbon C 11 metformin, the metformin moiety targets and binds to cancer cells; in turn, the compound is taken up by cancer cells. Upon PET, metformin distribution into cancer cells can be visualized, which allows for a prediction of the anti-cancer efficacy of metformin, based on tumor cell uptake. Metformin transport, such as uptake into cancer cells, appears to be correlated with the expression of organic cation transporters (OCT) 1-3, multidrug and toxin extrusion (MATE) 1 and 2, and plasma membrane monoamine transporter (PMAT). OCTs, MATEs and PMAT play a key role in the distribution and excretion of organic cationic compounds.
A radiopharmaceutical agent composed of an orally available, small-molecule antagonist of MDM2 (mouse double minute 2; Mdm2 p53 binding protein homolog), and labeled with the radioisotope carbon C 13, with potential use for evaluating the distribution patterns, metabolism and excretion of idasanutlin using nuclear magnetic resonance (NMR) spectroscopy. Upon administration, idasanutlin binds to MDM2 blocking the interaction between the MDM2 protein and the transcriptional activation domain of the tumor suppressor protein p53. By preventing the MDM2-p53 interaction, p53 is not enzymatically degraded and the transcriptional activity of p53 is restored. This may lead to p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger nuclear phosphoprotein and negative regulator of the p53 pathway, is often overexpressed in cancer cells and has been implicated in cancer cell proliferation and survival. . Labeling of idasanutlin with the radioactive tracer carbon C 13 permits the evaluation of idasanutlin's distribution patterns, including binding to and uptake by tumors, metabolism and excretion. This may aid in the understanding of the bioactivity of this agent.
A radiopharmaceutical agent composed of an orally available, small-molecule antagonist of MDM2 (mouse double minute 2; Mdm2 p53 binding protein homolog), and labeled with the radioisotope carbon C 14, with potential use for evaluating the pharmacokinetics of idasanutlin. Upon oral administration, idasanutlin binds to MDM2 blocking the interaction between the MDM2 protein and the transcriptional activation domain of the tumor suppressor protein p53. By preventing the MDM2-p53 interaction, p53 is not enzymatically degraded and the transcriptional activity of p53 is restored. This may lead to p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger nuclear phosphoprotein and negative regulator of the p53 pathway, is often overexpressed in cancer cells and has been implicated in cancer cell proliferation and survival. . Labeling of idasanutlin with the radioactive tracer carbon C 14 permits the evaluation of idasanutlin's pharmacokinetic profile, including its absorption, distribution, metabolism, and excretion (ADME).
A radioconjugate composed of ASP8273, an orally available, third-generation, mutant-selective, irreversible epidermal growth factor receptor (EGFR) inhibitor, labeled with the radioisotope carbon C 14, with potential use for evaluating the pharmacokinetic profile of ASP8273 during positron emission tomography (PET). Upon administration of carbon C 14 ASP8273, ASP8273 targets, covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M mutant form. Labeling of ASP8273 with the radioactive tracer carbon C 14 permits the evaluation of this agent's pharmacokinetic profile, including its absorption, distribution, metabolism, and excretion (ADME) using PET.
A finding indicating that a prostate carcinoma continues to grow despite the surgical removal of the testes or medical intervention to block androgen production.
A morphologic finding indicating the presence of a high-grade cellular component adjacent to or admixed with a low-grade cellular infiltarte.
An anaplastic large cell lymphoma, ALK-negative, arising from the central nervous system.
An anaplastic large cell lymphoma, ALK-positive, arising from the central nervous system.
An angiolipoma that arises from the central nervous system.
Intracranial and/or spinal involvement by desmoid-type fibromatosis.
A central nervous system embryonal neoplasm characterized by the presence of histological features consistent with atypical teratoid/rhabdoid tumor and absence of mutations of the INI1 gene or SMARCA4 (BRG1) gene.
A low-grade malignant blood vessel neoplasm that arises from the central nervous system. It is characterized by the presence of epithelioid endothelial cells.
Rare involvement of the central nervous system by Erdheim-Chester disease.
A rare Ewing sarcoma/peripheral primitive neuroectodermal tumor that affects the central nervous system either as a primary dural neoplasm or by direct extension from adjacent soft tissues or bone.
A rare extranodal B-cell non-Hodgkin lymphoma that affects the central nervous system. It is characterized by the presence of lymphoma cells exclusively in the lumina of small vessels, particularly capillaries.
Rare involvement of the central nervous system by Langerhans cell histiocytosis.
A primary central nervous system non-Hodgkin lymphoma derived from mature or post-thymic T-cells or NK-cells.
A mesenchymal chondrosarcoma that arises from the central nervous system.
A rare myofibroblastoma affecting the central nervous system.
A solitary fibrous tumor/hemangiopericytoma that arises from the central nervous system. It corresponds most often to the collagenous and low cellularity spindle cell tumor which was diagnosed as central nervous system solitary fibrous tumor in the past.
A solitary fibrous tumor/hemangiopericytoma that arises from the central nervous system. It corresponds to the more cellular, less collagenous tumor with plump cells and staghorn vasculature which was diagnosed as central nervous system hemangiopericytoma in the past.
A mesenchymal, non-meningothelial neoplasm arising from the central nervous system. It is characterized by a collagenous and low cellularity spindle cell and/or hemangiopericytomatous histopathological pattern, recurrent intrachromosomal rearrangement on chromosome 12q that results in the fusion of the NAB2 and STAT6 genes, high recurrence rates, and long-term risk of systemic metastasis.
A rare undifferentiated pleomorphic sarcoma (formerly known as malignant fibrous histiocytoma) involving the central nervous system.
An ependymal tumor affecting the cerebellum.
An ependymal tumor affecting the cerebellum and brain stem.
An ependymal tumor affecting the cerebellum and fourth ventricle and the brain.
An ependymal tumor affecting the cerebellum and a brain ventricle.
An ependymal tumor affecting the cerebellum, brain stem, and the cervical region of spinal cord.
A modulator of cereblon (CRBN), which is part of the cullin 4-RING E3 ubiquitin ligase complex (CRL4-CRBN E3 ubiquitin ligase; CUL4-CRBN E3 ubiquitin ligase), with potential immunomodulating and pro-apoptotic activities. Upon administration, CC-90009 specifically binds to CRBN, thereby affecting the activity of the ubiquitin E3 ligase complex. This leads to the ubiquitination of certain substrate proteins and induces the proteasome-mediated degradation of certain transcription factors, including Ikaros (IKZF1) and Aiolos (IKZF3), which are transcriptional repressors in T-cells. This reduces the levels of these transcription factors, and modulates the activity of the immune system, which may include the activation of T-lymphocytes. In addition, this downregulates the expression of other proteins, including interferon regulatory factor 4 (IRF4) and c-myc, which plays a key role in the proliferation of certain cancer cell types. CRBN, the substrate recognition component of the E3 ubiquitin ligase complex, plays a key role in the ubiquitination of certain proteins.
A finding about one or more characteristics of cervical lymph nodes and unknown primary tumors, following the rules of the TNM AJCC v8 classification system. It applies to squamous cell carcinoma and salivary gland carcinoma of all head and neck sites except HPV-related oropharynx cancer, nasopharynx cancer, melanoma, thyroid carcinoma, and sarcoma. Staging of the patient who presents with an occult primary tumor and EBV-unrelated and HPV-unrelated metastatic cervical lymphadenopathy is also included. (from AJCC 8th Ed.)
An ependymal tumor arising from the cervical region of spinal cord.
An ependymal tumor affecting the spinal cord in the cervical and lumbosacral regions.
An ependymal tumor affecting the spinal cord in the cervical and thoracic regions.
An ependymal tumor affecting the spinal cord in the cervical, thoracic, and lumbosacral regions.
A melanoma that occurs during childhood.
T acute lymphoblastic leukemia in childhood which is not growing and responds to treatment.
An irregularity in the structure of chromosome 17.
A chromosomal abnormality where one copy of the short arm of chromosome 3 has been deleted.
Chronic myelomonocytic leukemia characterized by the presence of eosinophilia, PDGFRB gene rearrangement, and t(5;12)(q31;p12).
A chronic myelomonocytic leukemia characterized by the presence of less than 5 percent blasts in the bone marrow and less than 2 percent blasts in the peripheral blood.
An area of the body subjected to consistent and repetitive sun exposure.
A severe form of congenital adrenal hyperplasia characterized by very low or absent activity of an enzyme in the steroidogenic pathway typically presenting early in life, and requiring life-long cortisol replacement.
Stage I includes: (T0, N0, M0); (T0, N1, M0); (T1, N0, M0); (T1, N1, M0); (T2, N0, M0); (T2, N1, M0). T0: No primary identified. T1: Tumor 2 cm or smaller in greatest dimension. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or more ipsilateral lymph nodes, none larger than 6 cm. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T0, N2, M0); (T1, N2, M0) ;(T2, N2, M0); (T3, N0, M0); (T3, N1, M0); (T3, N2, M0). T0: No primary identified. T1: Tumor 2 cm or smaller in greatest dimension. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. T3: Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or more ipsilateral lymph nodes, none larger than 6 cm. N2: Tumor with contralateral or bilateral lymph nodes metastasis, none larger than 6 cm. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T0, N3, M0); (T1, N3, M0); (T2, N3, M0); (T3, N3, M0); (T4, N0, M0); (T4, N1, M0); (T4, N2, M0); (T4, N3, M0). T0: No primary identified. T1: Tumor 2 cm or smaller in greatest dimension. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. T3: Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. T4: Tumor with moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible or beyond. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or more ipsilateral lymph nodes, none larger than 6 cm. N2: Tumor with contralateral or bilateral lymph nodes metastasis, none larger than 6 cm. N3: Tumor with lymph node(s) metastasis, larger than 6 cm. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis. (AJCC 8th ed.)
Ovarian failure, the cause of which is present at birth.
Testicular failure, the cause of which is present at birth.
Durable or long-term complete hematologic response. Time frames that define durability of complete hematologic response vary for different hematologic malignancies.
Mutations in the genes that encode proteins found in the core binding factor (CBF) complex. These genes may be involved in chromosomal rearrangements that are associated with acute myeloid leukemia.
A group of sclerosing bone dysplasias characterized by pronounced sclerosis of the cranial vault and the long bones, resulting in increased cortical bone density. Most cases are caused by mutation(s) in the SOST or LRP5 genes, encoding sclerostin and low-density lipoprotein receptor-related protein 5, respectively. Other genes have been implicated, and some cases have been described, but do not yet have identified genetic mutations.
A therapeutic vaccine composed of a synthetic peptide consisting of amino acids 11 through 19 of the viral oncoprotein human papillomavirus (HPV) subtype 16 E7 (HPV16-E7 11-19), with potential antineoplastic and immunostimulating activities. Immunization with the DPX-E7 HPV vaccine may stimulate the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the HPV16-E7 protein. HPV type 16 plays a key role in the carcinogenesis of certain cancers.
Impairment in the intracellular synthesis of thyroglobulin.
Impairment in the intracellular transport of thyroglobulin.
A change in the nucleotide sequence of the BARD1 gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the BRIP1 gene that is associated with increased risk of disease.
A mutation that appears in the genome of the germ cells and is associated with increased risk of disease.
A change in the nucleotide sequence of the MSH6 gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the PALB2 gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the PMS2 gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the RAD51C gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the RAD51D gene that is associated with increased risk of disease.
Any agent that inhibits or prevents DNA methylation or agents that promote the removal of methyl groups from DNA.
A photosensitizing agent composed of four sub-porphyrin derivatives, methoxyethy-hydroxyethyl-dipropionic, di-methoxyethyl-dipropionic, hydroxyethy-vinyl-dipropionic and methoxyethy-vinyl-dipropionic, with potential photosensitizing activity upon photodynamic therapy (PDT) and potential diagnostic imaging activity. Upon intravenous administration, deuteporfin preferentially targets and accumulates in cancer cells, especially those in the lymphatic system. Following photoactivation with an appropriate wavelength, deuteporfin generates highly cytotoxic singlet oxygen species, and induces oxidative stress that results in the damage and death of cancer cells. In addition, deuteporfin could be used as a tracer in near-infrared (NIR) fluorescence lymph node mapping.
A response indicating that an individual usually uses an aid or device for dressing, such as a button hook or zipper pull.
A subjective score of 0 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 10 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 1 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 2 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 3 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 4 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 6 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 7 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 8 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 9 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
KATP-associated hyperinsulinism affecting all pancreatic beta cells.
A relatively slow growing diffuse leptomeningeal neoplasm usually affecting children and adolescents. It is characterized by the presence of clear glial neoplastic cells reminiscent of oligodendroglioma. A neuronal component may be present. The prognosis is variable.
A deletion of the long (q) arm of chromosome 18 near one end of the chromosome. Manifestations of this disorder are varied and can commonly include short stature, hypotonia, hearing loss, clubfoot or rocker-bottom feet, eye movement disorders and other vision problems, cleft palate, hypothyroidism, congenital heart defects, kidney problems, genital and skin abnormalities. Most cases are the result of a de novo deletion and are not inherited.
A subjective score of 0 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 10 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 1 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 2 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 3 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 4 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 5 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 6 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 7 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
A subjective score of 9 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
An orally available third-generation and selective inhibitor of certain epidermal growth factor receptor (EGFR) activating mutations, including the resistance mutation T790M, and the L858R and del 19 mutations, with potential antineoplastic activity. Upon administration, the EGFR mutant-specific inhibitor CK-101 specifically and covalently binds to and inhibits selective EGFR mutations, with particularly high selectivity against the T790M mutation, which prevents EGFR mutant-mediated signaling and leads to cell death in EGFR mutant-expressing tumor cells. Compared to some other EGFR inhibitors, CK-101 may have therapeutic benefits in tumors with T790M-mediated drug resistance. This agent shows minimal activity against wild-type EGFR (WT EGFR), and does not cause dose-limiting toxicities that occur during the use of non-selective EGFR inhibitors, which also inhibit WT EGFR. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
A molecular abnormality indicating that the epidermal growth factor receptor protein has been localized to the membrane of an internal cellular compartment.
An orally available inhibitor of the epidermal growth factor receptor (EGFR) mutant form T790M, with potential antineoplastic activity. EGFR T790M antagonist BPI-15086 specifically binds to and inhibits EGFR T790M, a secondarily acquired resistance mutation, which prevents EGFR-mediated signaling and leads to cell death in EGFR T790M-expressing tumor cells. EGFR, a receptor tyrosine kinase that is mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
A molecular genetic abnormality indicating the presence of multiple copies of the EMSY gene.
A molecular abnormality indicating the presence of an abnormally high level of the ephrin type-A receptor 2 protein.
A change in the nucleotide sequence of the ERCC2 gene.
An orally available inhibitor of extracellular signal-regulated kinase (ERK) 1 and 2, with potential antineoplastic activity. Upon oral administration, LY3214996 inhibits both ERK 1 and 2, thereby preventing the activation of mitogen-activated protein kinase (MAPK)/ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent tumor cell proliferation and survival. The MAPK/ERK pathway is often upregulated in a variety of tumor cell types and plays a key role in tumor cell proliferation, differentiation and survival.
T acute lymphoblastic leukemia in which the blasts have unique immunophenotypic and genetic characteristics suggesting only limited early T-cell differentiation.
An autosomal recessive skeletal dysplasia caused by mutation(s) in the PTH1R gene, encoding parathyroid hormone/parathyroid hormone-related peptide receptor. This condition is characterized by severely delayed skeletal maturation, as well as by abnormal modeling of the bones in the hands and feet, abnormal persistence of cartilage in the pelvis, and mild growth retardation. Calcium and phosphate concentrations are normal.
An indication that the subject has fulfilled the criteria needed to continue to the next study period.
A central nervous system embryonal neoplasm characterized by the presence of histological features consistent with embryonal tumor with multilayered rosettes and absence of C19MC amplification.
A cellular droplet comprising fibrin degradation products or intracytoplasmic proteinaceous accumulations that can be stained by eosin.
An ependymal tumor affecting the brain and spinal cord.
Derangement of the thyroid gland or thyroid hormone metabolism that is unaccompanied by signs or symptoms of hypothyroidism or hyperthyroidism.
A mammographic finding of extremely dense breast composition, as defined by the visually estimated content of fibroglandular-density tissue within the breast, based on updated editions of the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS).
A subjective response indicating that something is extremely poor.
A molecular genetic abnormality indicating the presence of multiple copies of the FANCA gene.
A change in the nucleotide sequence of the FANCA gene.
A molecular genetic abnormality indicating the presence of multiple copies of the FANCC gene.
A change in the nucleotide sequence of the FANCD2 gene.
A change in the nucleotide sequence of the FANCE gene.
A change in the nucleotide sequence of the FANCF gene.
A change in the nucleotide sequence of the FANCM gene.
A change in the nucleotide sequence of the FBXW7 gene.
A change in the nucleotide sequence of the FGFR1 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the FGFR3 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the FLT1 gene.
A change in the nucleotide sequence of the FLT1 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the FLT4 gene.
A change in the nucleotide sequence of the FLT4 gene.
Presence of inactivating antibodies to fibrinogen (factor I) in the blood.
Presence of inactivating antibodies to prothrombin (factor II) in the blood.
Presence of inactivating antibodies to tissue factor (factor III) in the blood.
Presence of inactivating antibodies to factor IX in the blood.
Presence of inactivating antibodies to factor V in the blood.
Presence of inactivating antibodies to factor VII in the blood.
Presence of inactivating antibodies to factor VIII in the blood.
Presence of inactivating antibodies to factor X in the blood.
Presence of inactivating antibodies to factor XI in the blood.
Presence of inactivating antibodies to factor XII in the blood.
Presence of inactivating antibodies to factor XIII in the blood.
A response indicating that an individual has fecal incontinence or requires enemas.
A lymphoma that occurs in cats. It is associated with exposure to feline leukemia virus and feline immunodeficiency virus.
Oral squamous cell carcinoma that occurs in a cat.
A radioconjugate containing the epidermal growth factor receptor (EGFR) kinase tracer ODS2004436 labeled with fluorine F 18 for potential tumor imaging using positron emission tomography (PET). Upon administration of fluorine F 18 ODS2004436, the ODS2004436 moiety selectively targets and binds to forms of EGFR that contain activating mutations. This allows the visualization of tumor cells expressing activating EGFR mutations using PET. This agent can also be utilized in the prediction of responsiveness to EGFR tyrosine kinase inhibitors (TKIs) and the selection of patients that respond well to those kinase inhibitors that specifically target forms of EGFR with activating mutations. EGFR-activating mutations play a key role in the development of certain tumors and in tumor resistance to a variety of antineoplastic agents.
A radioconjugate composed of the paired helical filament (PHF) tau binding agent T807, a benzimidazole pyrimidine derivative, conjugated to the radioisotope fluorine F 18, with potential tau positron emission tomography (PET) imaging activity. Upon administration of fluorine F18 T807, the T807 moiety targets and binds to PHF-tau in the brain, which allows PET imaging of PHF-tau and analysis of phosphorylated PHF-tau aggregates (neurofibrillary tangles). Increased levels of PHF-tau and neurofibrillary tangles are correlated with the cognitive decline seen in neurodegenerative diseases, such as dementia, Alzheimer's disease (AD) and chemotherapy-induced cognitive impairment (CICI).
KATP-associated hyperinsulinism in which there is an area of adenomatous beta-cell hyperplasia. This condition results from paternal recessive mutation(s) in either the ABCC8 or the KCNJ11 gene and paternal uniparental isodisomy of chromosome region 11p15 with loss of tumor suppressor genes expressed from the maternally inherited chromosome.
Loss of subcutaneous fat confined to small area(s) of the body.
A response indicating that a form was not presented or mail to a parent.
An ependymal tumor arising from the fourth ventricle of the brain.
An ependymal tumor affecting the fourth ventricle and the brain stem.
A response indicating frequent disagreement.
An ependymal tumor affecting the frontal lobe of the brain.
An ependymal tumor affecting the frontal and parietal lobes of the brain.
A molecular genetic abnormality indicating the presence of a mutation in exon 2 of the GATA1 gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 3 of the GATA1 gene.
A change in the nucleotide sequence of the GATA2 gene.
A cytogenetic abnormality that refers to allelic gain within the chromosomal region 1q21.
A radiotracer composed of a bone targeting agent P15-041 linked to the radioisotope gallium Ga 68, with potential imaging activity upon positron emission tomography (PET)/computed tomography (CT). Upon administration, the P15-041 moiety targets, through an as of yet unknown mechanism of action, a certain target expressed by bone and, upon PET/CT, bone metastases can be imaged.
A radiolabeled recombinant EGFR-specific affibody molecule composed of an epidermal growth factor receptor (EGFR)-targeting protein, the anti-EGFR affibody ZEGFR:1907 with an acetylated cysteine (Ac-Cys) at the N terminal of the affibody, and conjugated to the radioisotope gallium Ga 68, via the chelating agent NODAGA (1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid), with potential use for imaging EGFR-expressing tumor cells upon positron emission tomography (PET). Upon administration of gallium Ga 68-NODAGA-Ac-Cys-ZEGFR:1907, the ZEGFR:1907 affibody molecule moiety targets and binds to the extracellular domain (ECD) of EGFR expressed on various tumor cell types. Upon PET, EGFR-expressing tumor cells can be visualized. EGFR, frequently overexpressed in cancers, plays important roles in cell proliferation, survival, adhesion, migration, and differentiation. The affibody protein scaffold is based on the Z-domain, which is derived from one of the immunoglobulin (Ig) G-binding domains of staphylococcal protein A.
A radiolabeled recombinant insulin-like growth factor 1 receptor (IGF-1R; IGF1R)-specific affibody ligand composed of an IGF1R-targeting protein, the anti-IGF1R affibody ZIGF-1R:4:40 with an acetylated cysteine (Ac-Cys) at the N terminal of the affibody, that is site-specifically conjugated with the chelating agent NODAGA (1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid), and labeled with the radioisotope gallium Ga 68, with potential use for imaging IGF1R-expressing tumor cells upon positron emission tomography (PET). Upon administration of gallium Ga 68-NODAGA-ZIGF-1R:4:40, the ZIGF-1R:4:40 affibody molecule moiety targets and binds to IGF1R expressed on various tumor cell types. Upon PET, IGF1R-expressing tumor cells can be visualized. IGF1R, frequently overexpressed in cancers, plays important roles in cell proliferation, survival, adhesion, migration, and differentiation. The affibody protein scaffold is based on the Z-domain, which is derived from one of the immunoglobulin (Ig) G-binding domains of staphylococcal protein A.
A squamous cell carcinoma that arises from the gingival mucosa. It presents as an ulcerated lesion or exophytic mass. The prognosis is usually poor.
An orally bioavailable, small-molecule, multitargeted tyrosine kinase inhibitor with potential antineoplastic activity. Glesatinib binds to and inhibits the phosphorylation of several receptor tyrosine kinases (RTKs), including the c-Met receptor (hepatocyte growth factor receptor); the Tek/Tie-2 receptor; vascular endothelial growth factor receptor (VEGFR) types 1, 2, and 3; and the macrophage-stimulating 1 receptor (MST1R or RON). Inhibition of these RTKs and their downstream signaling pathways may result in the inhibition of tumor angiogenesis and tumor cell proliferation in tumors overexpressing these RTKs.
Hyperinsulinism due to activating mutation(s) in the gene GCK, encoding glucokinase.
A glioma arising from the central nervous system. This category includes diffuse astrocytoma, ependymoma, oligodendroglioma, and oligoastrocytoma.
A vaccine composed of a peptide derived from histone H3.3 containing the amino acid substitution mutation lysine (Lys) 27-to-methionine (H3.3K27M), with potential immunoactivating and antineoplastic activities. Upon administration of the H3.3K27M-specific peptide vaccine, the immune system may exert a cytotoxic T-lymphocyte (CTL)-mediated immune response against H3.3K27M-expressing tumor cells. The H3.3K27M mutation alters the methylation and acetylation profile of the histone H3 variant H3.3 at Lys 27. Modification of H3.3 at Lys 27 regulates gene expression, and the H3.3K27M mutation occurs in a variety of cancer cell types.
An immunotherapeutic vaccine composed of the immunoadjuvant alpha-galactosylceramide (a-GC) and autologous antigen presenting cells (APCs), specifically B-lymphocytes and monocytes transfected with an adenoviral vector that expresses the tumor-associated antigens (TAAs) E6 and E7 derived from human papillomavirus (HPV) types 16 and 18 (HPV-16/18 E6/E7), with potential immunostimulating and antineoplastic activities. Upon administration of BVAC-C, the APCs stimulate the immune system to mount a TAA-specific cytotoxic T-lymphocyte (CTL) response, as well as natural killer (NK) cell, NK T-cell (NKT), helper T-cell and antibody-mediated immune responses, against the tumor cells. This directly or indirectly kills the TAA-expressing tumor cells. HPV-16/18 E6/E7 are overexpressed on certain tumor cell types and play key roles in tumor cell proliferation. a-GC, an NKT cell ligand, is used to specifically stimulate NKT cells and to further stimulate an anti-tumor immune response.
A clinical finding about one or more characteristics of HPV-mediated (p16-positive) oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of HPV-mediated (p16-positive) oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of HPV-mediated (p16-positive) oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of HPV-mediated (p16-positive) oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of HPV-mediated (p16-positive) oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of HPV-mediated (p16-positive) oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of HPV-mediated (p16-positive) oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system. Oropharyngeal cancers which are p16-negative are staged according to the classification for oropharynx (p16-negative) and hypopharynx cancers. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with distant metastasis. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with metastasis in one or more ipsilateral lymph nodes, none larger than 6 cm. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with contralateral or bilateral lymph node metastasis, none larger than 6 cm. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with lymph node(s) metastasis, larger than 6 cm. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with metastasis in four or fewer lymph nodes. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with metastasis in more than four lymph nodes. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
No primary identified. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with tumor 2 cm or smaller in greatest dimension. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with tumor larger than 2 cm but not larger than 4 cm in greatest dimension. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. (from AJCC 8th Ed.)
HPV-mediated (p16-positive) oropharyngeal cancer with moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible or beyond. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx. (from AJCC 8th Ed.)
A term that refers to the clinical staging of HPV-mediated (p16-positive) oropharyngeal carcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the pathologic staging of HPV-mediated (p16-positive) oropharyngeal carcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the staging of HPV-mediated (p16-positive) oropharyngeal carcinoma according to the American Joint Committee on Cancer, 8th edition.
A clinical finding about one or more characteristics of head and neck cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of head and neck cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of head and neck cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of head and neck cancer, following the rules of the TNM AJCC v8 classification system.
Head and neck cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE (extranodal extension)(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, ENE(-). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a single ipsilateral or contralateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastases in a single ipsilateral lymph node ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes, any with ENE(+). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a single ipsilateral lymph node ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes, any with ENE(+). (from AJCC 8th Ed.)
Head and neck cancer in which no regional lymph node metastases are detected. (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (extranodal extension)(-). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a single ipsilateral lymph node 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, ENE(-). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a single ipsilateral lymph node 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Head and neck cancer with metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); (from AJCC 8th Ed.)
Head and neck cancer with metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastases in a single ipsilateral lymph node larger than 3 cm and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes, any with ENE(+). (from AJCC 8th Ed.)
Head and neck cancer with metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes, any with ENE(+). (from AJCC 8th Ed.)
A response indicating that an individual did not have hearing problems or hearing problems did not interfere with activities.
Hyperinsulinism due to mutation(s) in the gene HNF1A, encoding the transcription factor hepatocyte nuclear factor 1-alpha. This condition may progress to diabetes later in life.
Hyperinsulinism due to mutation(s) in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4-alpha. This condition may progress to diabetes later in life.
An autosomal recessive, inherited coagulation disorder characterized by the partial or complete absence of tissue factor (factor III) activity in the blood.
A mammographic finding of heterogeneously dense breast composition, as defined by the visually estimated content of fibroglandular-density tissue within the breast, based on updated editions of the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS).
Decreased activity of hexose-6-phosphatase due to autosomal recessive mutation(s) in the H6PD gene. This enzyme is necessary to generate NADPH, a cofactor in the 11-beta-hydroxysteroid dehydrogenase pathway required for conversion of cortisone to cortisol. The condition is characterized by hyperandrogenism as a result of increased adrenocorticotropic hormone stimulation of the adrenal gland due to failure of cortisol-mediated down-regulation, and is clinically indistinguishable from 11-beta HSD type 1 deficiency.
Skin that is abnormally dry and stiff, lacking pliancy and closely adhered to the underlying flesh.
A response indicating a high level of confidence.
A rare B-cell non-Hodgkin lymphoma that is characterized by the abnormal rearrangement of MYC gene, BCL2 gene, and BCL6 gene. Patients with this type of lymphoma usually respond poorly to standard treatments and have a poor prognosis.
A gel-based formulation composed of a very dilute solution of hydrogen peroxide (H2O2) combined with hyaluronic acid (HA), with potential radiosensitizing activity. Upon intratumoral injection and slow-release (SR) of H2O2 from the gel, H2O2 releases oxygen and inactivates anti-oxidative enzymes, thereby increasing the oxygen concentration in the tumor environment, which increases the efficacy of radiotherapeutic treatment. HA increases viscosity of the formulation and allows for the SR of H2O2; as compared to the injection of H2O2 alone, the addition of HA decreases diffusion of H2O2 to surrounding areas and enhances intratumoral H2O2 concentration over an increased period of time. Hypoxic tumors show a decreased response to radiotherapy; thus, increasing oxygen content increases tumor response to radiotherapy.
Transient hypoglycemia that occurs in the infant of a diabetic mother due to increased postnatal insulin release as a result of in utero exposure to maternal hyperglycemia.
Hypogonadotropic hypogonadism with congenital adrenal hypoplasia associated with mutation(s) in the NR0B1 gene (on the X chromosome).
A clinical finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A clinical finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to all cancers of the hypopharynx. Minor salivary gland carcinomas and neuroendocrine carcinomas of the hypopharynx are included in this classification. (from AJCC 8th Ed.)
Hypopharyngeal cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Hypopharyngeal cancer with distant metastasis. (from AJCC 8th Ed.)
Hypopharyngeal cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (-). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in any node(s) and clinically overt ENE(+). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in any node(s) and clinically overt ENE(+). (from AJCC 8th Ed.)
Hypopharyngeal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes any with ENE(+). (from AJCC 8th Ed.)
Hypopharyngeal cancer with metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes any with ENE(+). (from AJCC 8th Ed.)
Hypopharyngeal cancer with tumor limited to one subsite of hypopharynx and/or 2 cm or smaller in greatest dimension. (from AJCC 8th Ed.)
Hypopharyngeal cancer with tumor invading more than one subsite of hypopharynx or an adjacent site, or measuring more than 2 cm but not more than 4 cm in greatest dimension without fixation of hemilarynx. (from AJCC 8th Ed.)
Hypopharyngeal cancer with tumor larger than 4 cm in greatest dimension or with fixation of hemilarynx or extension to esophagus. (from AJCC 8th Ed.)
Hypopharyngeal cancer with moderately advanced or very advanced local disease. (from AJCC 8th Ed.)
Hypopharyngeal cancer with moderately advanced local disease. Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue. Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. (from AJCC 8th Ed.)
Hypopharyngeal cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Hypopharyngeal cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
A term that refers to the staging of hypopharyngeal carcinoma according to the American Joint Committee on Cancer, 8th edition.
An orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP+] soluble) with a mutation at arginine (R) 132, IDH1(R132), with potential antineoplastic activity. Upon administration, IDH-1 inhibitor FT-2102 specifically inhibits IDH1(R132), thereby inhibiting the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH(R132). IDH1(R132) mutations are highly expressed in certain malignancies, including gliomas; they initiate and drive cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG.
A nucleotide substitution at position 356 of the coding sequence of the IDH1 gene where guanine has been mutated to adenine.
A nucleotide substitution at position 394 of the coding sequence of the IDH1 gene where cytosine has been mutated to adenine.
A nucleotide substitution at position 394 of the coding sequence of the IDH1 gene where cytosine has been mutated to guanine.
A nucleotide substitution at position 394 of the coding sequence of the IDH1 gene where cytosine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 394 and 395 of the coding sequence of the IDH1 gene has changed from cytosine-guanine to thymine-cytosine.
A nucleotide substitution at position 395 of the coding sequence of the IDH1 gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 119 in the isocitrate dehydrogenase [NADP] cytoplasmic protein where arginine has been replaced by glutamine.
A change in the amino acid residue at position 132 in the isocitrate dehydrogenase [NADP] cytoplasmic protein where arginine has been replaced by cysteine.
A change in the amino acid residue at position 132 in the isocitrate dehydrogenase [NADP] cytoplasmic protein where arginine has been replaced by leucine.
A change in the amino acid residue at position 132 in the isocitrate dehydrogenase [NADP] cytoplasmic protein where arginine has been replaced by serine.
A nucleotide substitution at position 514 of the coding sequence of the IDH2 gene where adenine has been mutated to guanine.
A nucleotide substitution at position 515 of the coding sequence of the IDH2 gene where guanine has been mutated to adenine.
A nucleotide substitution at position 515 of the coding sequence of the IDH2 gene where guanine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 515 and 516 of the coding sequence of the IDH1 gene has changed from guanine-guanine to adenine-adenine.
A change in the amino acid residue at position 172 in the isocitrate dehydrogenase [NADP], mitochondrial protein where arginine has been replaced by glycine.
A change in the amino acid residue at position 172 in the isocitrate dehydrogenase [NADP], mitochondrial protein where arginine has been replaced by lysine.
A change in the amino acid residue at position 172 in the isocitrate dehydrogenase [NADP], mitochondrial protein where arginine has been replaced by methionine.
An orally available inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with potential immunomodulating and antineoplastic activities. Upon administration, IDO1 inhibitor KHK2455 targets and binds to IDO1, an enzyme responsible for the oxidation of tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, KHK2455 increases and restores the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes. KHK2455 also induces increased interferon (IFN) production, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may inhibit the growth of IDO1-expressing tumor cells. IDO1, a cytosolic enzyme responsible for tryptophan catabolism and the conversion of tryptophan into kynurenine, is overexpressed by a variety of tumor cell types and antigen presenting cells (APCs); it plays an important role in immunosuppression. Tryptophan depletion inhibits T-lymphocyte proliferation and activation, and subsequently suppresses the immune system.
A fusion protein consisting of the cytokine interleukin-4 (IL-4) linked to a truncated form of Pseudomonas exotoxin with potential antineoplastic activity. Upon specific, high-affinity binding to IL-4 receptors located on the tumor cell surface., IL4-Pseudomonas exotoxin fusion protein MDNA55 is internalized; the exotoxin moiety then binds to translation elongation factor 2 (EF-2), which may result in ADP ribosylation, deactivation of EF-2, inhibition of protein synthesis, and tumor cell apoptosis. The Pseudomonas exotoxin moiety of this agent has been engineered to reduce non-specific binding to cells expressing its receptor, the multiligand cell surface receptor alpha 2-macroglobulin receptor/low-density lipoprotein receptor-related protein (alpha 2MR/LRP). IL-4R is a type I transmembrane protein that binds IL-4 and IL-13 and may be overexpressed by cancers such as renal cell carcinoma and glioma.
Contrasexual pubertal development caused by medical intervention.
Hypoparathyroidism resulting from medical treatment or intervention.
Primary hypothyroidism due to medical or surgical treatment.
Ketotic hypoglycemia that usually occurs in young, thin children in association with infection or fasting, and which typically resolves by age 6-8 years.
A proprietary, suppository-based formulation composed of idronoxil, a synthetic flavonoid derivative, surrounded by a proprietary lipid that protects idronoxil from phase 2 degradation, with potential chemo- and radio-sensitizing activities. Upon administration, idronoxil blocks the activity of ecto-NOX disulfide-thiol exchanger 2 (ENOX2; tNOX), a tumor-specific external NADH oxidase that maintains the transmembrane electron potential across the plasma membrane and is overexpressed in certain cancer cell types while absent in normal, healthy cells. Loss of this potential directly inhibits certain pro-survival signal transduction pathways, such as the PARP1/PI3 kinase/Akt signaling pathway. The inhibition of these pathways prevents resistance to standard chemo- and radio-therapy and makes tumor cells more susceptible to the anti-tumor activity of conventional chemotherapeutic agents and radiotherapy. The formulation prevents detoxification of idronoxil to an inactive form by bypassing phase 2 metabolism; this increases idronoxil's bioavailability as compared to idronoxil alone.
A marked increase in contrast enhancement that is not due to actual tumor growth, but that may be due to a reaction to immunotherapy.
Mutation(s) in the TSHR gene, resulting in decreased function of the thyroid stimulating hormone receptor.
A response indicating that an individual is independent of others for bathing in the tub or shower.
A response indicating that an individual can eat independently of help from others when food is provided within reach.
A response indicating that an individual can use the toilet independently of help from others.
A non-neoplastic T-cell lymphoproliferation that may mimic T-lymphoblastic lymphoma. It usually involves the lymphoid tissues of the upper aerodigestive tract. It recurs locally, but systemic dissemination is rare.
An ependymal tumor arising from the infratentorial region of the brain.
An ependymal tumor affecting the infratentorial region of the brain and the spinal cord.
Insulin resistance caused by inactivating mutation(s) in the INSR gene encoding the insulin receptor.
A benign fibrous histiocytoma involving the dura or cranial bone.
A radioconjugate composed of MIP-1095, a urea-based ligand for the tumor-associated antigen (TAA) prostate-specific membrane antigen (PSMA) radiolabeled with iodine I 131 (I131), with potential antineoplastic activity. Upon administration of iodine I 131 MIP-1095, the MIP-1095 moiety selectively targets and binds to the extracellular domain of PSMA, thereby delivering cytotoxic iodine I 131 specifically to PSMA-expressing cancer cells. PSMA is a transmembrane glycoprotein that is highly expressed by malignant prostate epithelial cells and certain other tumor cells.
A subtype of micronodular adrenal hyperplasia, characterized by multiple non-pigmented nodules.
A change in the nucleotide sequence of the JAK1 gene.
Any substance that inhibits the biological action of tyrosine-protein kinase JAK1, an enzyme that plays a key role in certain types of cancer and cytokine signaling.
A response indicating that an individual usually uses a jar opener for jars that were previously opened.
Diabetes mellitus caused by activating mutation(s) in genes (KNCJ11 and/or ABCC8) encoding either of the 2 proteins (Kir6.2 and/or SUR1) that make up the pancreatic beta cell adenosine triphosphate-sensitive potassium channel, which is crucial for the regulation of glucose-induced insulin secretion.
Hyperinsulinism caused by non-functional beta-cell ATP-sensitive potassium channels due to inactivating mutation(s) in either the ABCC8 or KCNJ11 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the KDR gene.
A change in the nucleotide sequence of the KDR gene.
A change in the nucleotide sequence of the KEAP1 gene.
A cell-based cancer vaccine composed dendritic cells (DC) that were matured in the presence of a synthetic complex comprised of polyinosinic-polycytidylic acid, poly-L-lysine double-stranded RNA, and carboxymethylcellulose (poly-ICLC), and then pulsed with peptides derived from the tumor-associated antigens (TAAs) cancer/testis antigen NY-ESO-1 and melanoma antigen recognized by T-cells (MART-1/Melan-A), which are linked to the immunostimulant and carrier protein keyhole limpet hemocyanin (KLH), with potential immunostimulatory and antineoplastic activities. Upon intradermal administration, the KLH/NY-ESO-1/MART-1 peptide-pulsed DC vaccine stimulates the immune system to mount an anti-tumor cytotoxic T-lymphocyte (CTL) response against NY-ESO-1/MART-1-expressing tumor cells, which may result in tumor cell lysis. NY-ESO-1 is expressed both in normal testes and on the surfaces of various tumor cells. MART-1 is expressed by melanoma cells. The adjuvant poly-ICLC, a ligand for toll-like receptor-3 (TLR-3), induces the release of cytokines that may help boost the immune response against the TAAs. KLH boosts the immune response against the TAA-expressing tumor cells.
A nucleotide substitution at position 436 of the coding sequence of the KRAS gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 146 in the GTPase Kras protein where alanine has been replaced by threonine.
Regions of hypermutation that are found in clusters and are localized to one or more hot spots in the genome.
Diabetes mellitus caused by activating mutation(s) in the KCNJ11 gene, encoding the inwardly rectifying Kir6.2 subunit of the pancreatic beta cell adenosine triphosphate-sensitive potassium channel. Note: Inactivating mutation(s) in the KCNJ11 gene result in hyperinsulinism.
An orally available inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, CC-90011 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4, respectively. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor (remove hyphen) suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes. LSD1, an enzyme belonging to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family that is overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival.
An orally available, irreversible inhibitor of lysine-specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, IMG-7289 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor suppressor genes. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; thus, inhibition of LSD1 also promotes H3K9 methylation and decreases transcription of these genes. Altogether, this may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, an enzyme belonging to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family is overexpressed in certain tumor cells and plays a key role in the regulation of gene expression, tumor cell growth and survival.
An orally available inhibitor of lysine specific histone demethylase 1 (KDM1A; LSD1), with potential antineoplastic activity. Upon administration, RO7051790 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4, respectively. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. In addition, LSD1 demethylates mono- or di-methylated H3K9, which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes. LSD1, an enzyme belonging to the flavin adenine dinucleotide (FAD)-dependent amine oxidase family, is overexpressed in certain tumor cells and plays a key role in in the regulation of gene expression, tumor cell growth and survival.
Absent or incomplete development of adrenal androgen-mediated secondary sexual characteristics.
A medulloblastoma composed of sheets of large cells mixed with cells characterized by marked nuclear pleomorphism and high mitotic activity.
An ependymal tumor arising from a lateral ventricle of the brain.
An ophthalmic gel formulation containing the synthetic amide-type anesthetic lidocaine, with potential analgesic activity. Upon ophthalmic application, the active ingredient lidocaine binds to and blocks voltage-gated sodium channels in neuronal cell membranes. Lidocaine-mediated stabilization of neuronal membranes inhibits the initiation and conduction of nerve impulses, which numbs the nerves, prevents the trigemino-cardiac reflex and produces a reversible local anesthesia.
A clinical finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A clinical finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v8 classification system. The assessment of the primary tumor is based on inspection and palpation of the oral cavity and neck. Additional studies may include CT, MRI, or ultrasound. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases. There is no pathologic M0 for lip and oral cavity cancer.
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v8 classification system. The pathologic staging is determined after the complete resection of the primary site and/or regional nodal dissection, followed by pathologic examination of the resected specimen(s). (from AJCC 8th Ed.)
A finding about one or more characteristics of lip and oral cavity cancer, following the rules of the TNM AJCC v8 classification system. Cutaneous squamous cell carcinoma of the vermilion lip, nonepithelial tumors such as those of lymphoid tissue, soft tissue, bone, cartilage, and mucosal melanoma are not included in this classification. (from AJCC 8th Ed.)
A term that refers to the staging of lip and oral cavity carcinoma according to the American Joint Committee on Cancer, 6th and 7th editions.
A term that refers to the staging of lip and oral cavity carcinoma according to the American Joint Committee on Cancer, 8th edition.
Lip and oral cavity cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Lip and oral cavity cancer with distant metastasis. (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, and ENE(-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, and ENE(-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in any node(s) and clinically overt ENE(+). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in any node(s) and clinically overt ENE(+). (from AJCC 8th Ed.)
Lip and oral cavity cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE (-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, ENE(-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or a single ipsilateral node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE (-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE (-); or in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral or bilateral lymph nodes any with ENE(+). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE (-). (from AJCC 8th Ed.)
Lip and oral cavity cancer with metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral or bilateral lymph nodes any with ENE(+). (from AJCC 8th Ed.)
Lip and oral cavity cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Lip and oral cavity cancer with tumor size 2 cm or less in greatest dimension and 5 mm or less depth of invasion (DOI). DOI is depth of invasion and not tumor thickness. (from AJCC 8th Ed.)
Lip and oral cavity cancer with tumor size 2 cm or less in greatest dimension, DOI greater than 5 mm and equal or less than 10 mm or tumor greater than 2 cm but 4 cm or less in greatest dimension and 10 mm or less DOI. (from AJCC 8th Ed.)
Lip and oral cavity cancer with tumor size greater than 4 cm or any tumor greater than 10 mm DOI. (from AJCC 8th Ed.)
Lip and oral cavity cancer with moderately advanced or very advanced local disease. (from AJCC 8th Ed.)
Lip and oral cavity cancer with moderately advanced local disease. For lip: Tumor invades through cortical bone or involves the inferior alveolar nerve, floor of mouth, or skin of face (i.e., chin or nose). For oral cavity: Tumor invades adjacent structures only (e.g., through cortical bone of the mandible or maxilla, or involves the maxillary sinus or skin of face). Note: Superficial erosion of bone/tooth socket (alone) by a gingival primary is not sufficient to classify a tumor as T4. (from AJCC 8th Ed.)
Lip and oral cavity cancer with very advanced local disease. Tumor invades masticator space, pterygoid plates, or skull base and/or encases the internal carotid artery. (from AJCC 8th Ed.)
Lip and oral cavity cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Lip and oral cavity cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
A finding indicating the formation of liquid areas in a tissue sample.
An orally bioavailable agonist of the nuclear receptor liver X receptor beta (LXRbeta; NR1H2; LXR-b), with potential immunomodulating and antineoplastic activities. Upon oral administration, LXRbeta agonist RGX-104 selectively targets and binds to LXRbeta, thereby activating LXRbeta-mediated signaling, leading to the transcription of certain tumor suppressor genes and the downregulation of certain tumor promoter genes. This particularly activates the expression of apolipoprotein E (ApoE), a tumor suppressor protein, in tumor cells and certain immune cells. This activates the innate immune system, resulting in depletion of immunosuppressive myeloid-derived suppressor cells (MDSCs), tumor cells and endothelial cells in the tumor microenvironment. This reverses immune evasion, enhances anti-tumor immune responses and inhibits proliferation of tumor cells. LXRbeta, a member of the oxysterol receptor family, which is in the nuclear receptor family of transcription factors, plays a key role in cholesterol transport, glucose metabolism and the modulation of inflammatory responses; activation of LXRbeta suppresses tumor cell invasion, angiogenesis, tumor progression, and metastasis in a variety of tumor cell types. The expression of the ApoE protein becomes silenced in human cancers as they grow, become invasive, and metastasize; ApoE silencing is related to reduced survival in cancer patients. The LXR-ApoE pathway regulates the ability of cancers to evade the immune system and recruit blood vessels.
A response indicating a low level of confidence.
An ependymal tumor arising from the lumbosacral region of spinal cord.
A proprietary, peptide cancer vaccine comprised of multiple peptides derived from human melanoma antigen A3 (MAGE-A3; MAGEA3), with potential immunostimulating and antineoplastic activities. Upon administration, MAGE-A3 multipeptide vaccine GL-0817 may stimulate the immune system to mount specific responses from B-cells, and CD4-positive and CD8-positive cells against tumor cells expressing MAGE-A3, resulting in tumor cell lysis. MAGE-A3, a tumor-associated antigen (TAA), is overexpressed by a variety of cancer cell types.
A molecular genetic abnormality indicating the presence of a splice site mutation that results in a loss of transcription of exon 14 of the MET gene.
A glioblastoma characterized by the absence of DNA methylation in the promoter region of the MGMT gene. It is associated with a poor outcome.
A change in the nucleotide sequence of the MRE11 gene.
A nucleotide substitution at position 1906 of the coding sequence of the MSH2 gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 636 in DNA mismatch repair protein Msh2 where alanine has been replaced by proline.
A variation in the amino acid sequence for DNA mismatch repair protein Msh2.
A molecularly distinct B-cell lymphoma reminiscent of Burkitt lymphoma. It is characterized by the absence of MYC translocation and the presence of chromosome 11q aberrations.
A cytogenetic finding indicating Philadelphia chromosome positivity less than or equal to 35% in a patient treated for chronic myelogenous leukemia, BCR-ABL1 positive.
A response indicating that an individual can transfer and sit, but needs major, physical help from one or two people.
A clinical finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A clinical finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of major salivary gland cancer, following the rules of the TNM AJCC v8 classification system. This classification does not apply to lymphomas and minor salivary gland cancers. (from AJCC 8th Ed.)
A term that refers to the staging of major salivary gland cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of major salivary gland cancer according to the American Joint Committee on Cancer, 8th edition.
Major salivary gland cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Major salivary gland cancer with distant metastasis. (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-), or in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in any node(s) with clinically overt ENE(+). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in any node(s) with clinically overt ENE(+). (from AJCC 8th Ed.)
Major salivary gland cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(+); or more than 3 cm but not more than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-), or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(+); or a single ipsilateral node more than 3 cm but not more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or multiple ipsilateral, contralateral, or bilateral nodes any with ENE(+). (from AJCC 8th Ed.)
Major salivary gland cancer with metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or multiple ipsilateral, contralateral, or bilateral nodes any with ENE(+). (from AJCC 8th Ed.)
Major salivary gland cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Major salivary gland cancer with no evidence of a primary tumor. (from AJCC 8th Ed.)
Major salivary gland cancer with tumor 2 cm or less in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. (from AJCC 8th Ed.)
Major salivary gland cancer with tumor more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. (from AJCC 8th Ed.)
Major salivary gland cancer with tumor more than 4 cm in greatest dimension, and/or tumor having extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. (from AJCC 8th Ed.)
Moderately advanced or very advanced major salivary gland cancer. (from AJCC 8th Ed.)
Moderately advanced major salivary gland cancer. Tumor invades skin, mandible, ear canal, and/or facial nerve. (from AJCC 8th Ed.)
Very advanced major salivary gland cancer. Tumor invades skull base and/or pterygoid plates and/or encases carotid artery. (from AJCC 8th Ed.)
Major salivary gland cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Major salivary gland cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
A traditional Persian medicine composed of Malva sylvestris (M. sylvestris) and Alcea digitata (A. digitata; Boiss), with potential use for the treatment of radiation- and chemotherapy-induced xerostomia, and potential immunomodulating, anti-oxidant and antimicrobial activities. Upon administration to the mouth, M. sylvestris/A. digitata herbal compound may lubricate the mouth and throat, and may improve the symptoms of dry mouth, thereby preventing tooth decay and improving chewing, eating, tasting, swallowing, and speaking. M. sylvestris/A. digitata herbal compound may also improve mucositis by modulating the immune system, thereby preventing infection, reducing inflammation and promoting wound healing.
A rare, low-grade carcinoma of the salivary gland with favorable clinical outcome. It usually arises from the parotid gland and less often from the minor salivary glands. It shares the same histopathologic features and molecular characteristics (ETV6 gene rearrangement) with secretory breast carcinoma.
A mammographic finding of heterogeneously or extremely dense breast composition, as defined by the visually estimated content of fibroglandular-density tissue within the breast, based on updated editions of the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS).
A term that refers to the classification of medulloblastomas according to their molecular characteristics.
Medulloblastoma not associated with activation of the WNT pathway or sonic hedgehog (SHH) pathway. MYC amplifications may be present. TP53 mutations are absent. Patients in this group are usually young children. The overall survival is the worst among all the molecular groups.
Medulloblastoma not associated with activation of the WNT pathway or sonic hedgehog (SHH) pathway. MYC amplifications are absent. TP53 mutations are absent. Chromosome 17 abnormalities may be present.
Medulloblastoma not associated with activation of the WNT pathway or sonic hedgehog (SHH) pathway. TP53 mutations are absent. This molecular subtype includes medulloblastomas numerically designated as ""group 3"" and ""group 4"".
A medulloblastoma which has not been further characterized.
Medulloblastoma associated with activation of the sonic hedgehog (SHH) pathway and the presence of TP53 mutations.
Medulloblastoma associated with activation of the sonic hedgehog (SHH) pathway and the absence of TP53 mutations.
A molecular subtype of medulloblastoma associated with activation of the sonic hedgehog (SHH) pathway. TP53 mutations may be present or absent. Patients in this group are young children and adults. Overall survival is variable and depends on the presence or absence of metastatic disease, histology, and the age at diagnosis.
An indication as to whether a malignancy has appeared at sites distant to the primary site of disease.
A malignant germ cell tumor which has spread from its original site of growth to another anatomic site.
A carcinoma that arises from the prostate gland and has spread to the soft tissues.
An autosomal recessive or sporadic form of adrenal hypoplasia congenita frequently associated with central nervous system anomalies including anencephaly and pituitary defects. Histologically the adrenal gland is distinguished by the absence of fetal adrenal cortex and the presence of a small amount of normal, permanent adult adrenal cortex.
A response indicating that an individual needs minor verbal or physical help to transfer.
Diabetes mellitus caused by mutation(s) in mitochondrial DNA .
Hyperinsulinism due to inactivating mutation(s) in the gene HADH, encoding mitochondrial (short-chain) hydroxyacyl-coenzyme A dehydrogenase, resulting in loss of inhibition of glutamate dehydrogenase (GDH). This condition is also characterized by protein-induced hypoglycemia, but in contrast to GLUD1-associated hyperinsulinism, hyperammonemia is absent.
Hyperinsulinism due to mutation(s) in the gene UCP2, encoding mitochondrial uncoupling protein 2, which plays a role in attenuating insulin secretion.
A modified version of vitamin D binding protein (VDBP; Gc protein) macrophage activator, with potential antineoplastic and anti-angiogenic activities. Upon administration, modified VDBP-macrophage activator EF-022, acting in a similar manner as VDBP-macrophage activating factor (GcMAF), is able to activate tumoricidal macrophages, thereby enhancing the killing and eradication of cancer cells. In addition, EF-022 may inhibit tumor cell proliferation, migration and angiogenesis. VDBP is a glycoprotein and precursor for macrophage activating factor (MAF), which promotes macrophage activation; however VDBP can be deglycosylated by serum alpha-N-acetylgalactosaminidase, which is secreted from cancerous cells, and cannot be converted to MAF. Thus, the macrophage activation cascade is often impaired in tumor cells and plays a key role in tumor immunosuppression. Modification of VDBP stabilizes MAF.
A mutation that occurs on one allele of a gene.
A therapeutic monoclonal antibody against an as of yet unidentified target expressed on mast cells and eosinophils. Upon administration, AK002 targets and binds to a receptor expressed on the surface of mast cells and eosinophils. This may induce antibody-dependent cell-mediated cytotoxicity (ADCC) against cells overexpressing the undisclosed receptor. This may reduce abnormal proliferation of mast cells and eosinophils, which play a key role in allergic and inflammatory responses.
A genetically heterogenous group of hyperinsulinemic conditions caused by mutation(s) in one of the many genes involved in the regulation of insulin secretion.
A cancer vaccine consisting of two immunogenic peptides derived from the cancer-testis antigen NY-ESO-1 and the melanoma differentiation antigen Melan-A (MART-1; Melanoma Antigen Recognized by T-cells 1), which are conjugated with the immunostimulant keyhole limpet hemocyanin (KLH) and emulsified in the immunoadjuvant Montanide ISA-51 VG, with potential immunomodulating and antineoplastic activities. Upon subcutaneous vaccination, the Montanide ISA-51 VG/KLH/NY-ESO-1/MART-1 peptide vaccine stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the NY-ESO-1 and Melan-A antigens, resulting in tumor cell lysis. NY-ESO-1 and Melan-A are overexpressed in a variety of tumor cell types. The surfactant mannide monooleate in Montanide ISA 51 VG is derived from vegetable-grade (VG) oleic acid that was purified from olive oil. KLH is a hapten carrier and serves as an immunostimulant to improve immune recognition.
A response indicating that something occurs more than half the time.
A malignant germ-cell neoplasm arising from pluripotent cells, including components from the epithelial germ-cell layer, which occurs in a mouse.
A condition characterized by Mullerian duct aplasia, unilateral renal dysplasia, and cervicothoracic anomalies. Other associated findings may include skeletal abnormalities (scoliosis, vertebral anomalies, rib malformations, spina bifida), and face and limb malformations (brachymesophalangy, ectrodactyly). Heart malformations may include valvular pulmonary stenosis, aortopulmonary window, atrial septal defect, and/or tetralogy of Fallot. Putative candidate genes such as HNF1B (17q12), LHX1 (17q12), SHOX (Xp22.33 and Yp11.32), TBX6 ( 16p11.2), and ITIH5 (10p14) may be implicated.
An architectural pattern characterized by the presence of neoplastic cells forming multiple nodules with prominent vacuolation.
A low-grade tumor affecting the cerebral hemispheres. It is composed of cells with glial and/or neuronal differentiation forming multiple nodules with prominent vacuolation.
A dendritic cell (DC) vaccine in which autologous DCs are loaded with multiple tumor-associated antigens (TAAs), with potential immunostimulating and antineoplastic activities. Upon re-infusion into the patient, the antigen-pulsed DCs stimulate the immune system to mount a specific cytotoxic T-lymphocyte (CTL) response against the TAA-expressing tumor cells.
A rare syndrome that refers to a constellation of anomalies resulting from multiple vascular disruption.
A myelodysplastic syndrome with ring sideroblasts and dysplastic changes involving only one myeloid cell lineage in the bone marrow.
A term that refers to myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasms, and acute myeloid leukemias that are associated with germ line mutations and are familial.
Rare myeloid neoplasms characterized by eosinophilia, bone marrow findings of left-shifted erythroid predominance, lymphoid aggregates, and often myelofibrosis, and the detection of t(8;9)(p22;p24.1) and PCM1-JAK2 fusion gene. Rare cases present as T- or B-acute lymphoblastic leukemia.
A change in the nucleotide sequence of the NFE2L2 gene.
A molecular abnormality indicating rearrangement of the NTRK2 gene.
A molecular abnormality indicating rearrangement of the NTRK3 gene.
A formulation composed of nanoparticle albumin-bound (nab) paclitaxel, which is an albumin-stabilized nanoparticle containing the natural taxane paclitaxel, non-covalently coated with rituximab, a recombinant chimeric murine/human antibody directed against the CD20 antigen found on B-lymphocytes, with potential antineoplastic activity. Upon administration of nab-paclitaxel/rituximab nanoparticle AR160, the rituximab moiety specifically binds to CD20 and targets this formulation to CD20-positive tumor cells. Paclitaxel binds to and stabilizes microtubules, which prevents depolymerization and inhibits cellular motility, mitosis, and replication. This leads to cell death of the CD20-expressing tumor cells that were targeted by this agent. The combination of albumin-stabilization and rituximab-targeting allows for higher efficacy and decreased paclitaxel-induced toxicity as it specifically targets CD20-expressing tumor cells. Rituximab may also induce complement-dependent cytotoxicity and antibody-dependent cellular toxicity.
A clinical finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of nasopharyngeal cancer, following the rules of the TNM AJCC v8 classification system. Epithelial tumors of the nasopharynx are staged using this staging system. Mucosal melanoma, lymphoma, and sarcoma of soft tissue, bone, and cartilage are not included in this classification. (from AJCC 8th Ed.)
Nasopharyngeal cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Nasopharyngeal cancer with distant metastasis. (from AJCC 8th Ed.)
Nasopharyngeal cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Nasopharyngeal cancer with unilateral metastasis in cervical lymph node(s), and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. (from AJCC 8th Ed.)
Nasopharyngeal cancer with bilateral metastasis in cervical lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. (from AJCC 8th Ed.)
Nasopharyngeal cancer with unilateral or bilateral metastasis in cervical lymph node(s), larger than 6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage. (from AJCC 8th Ed.)
Nasopharyngeal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
No tumor identified, but EBV-positive cervical node(s) involvement is present. (from AJCC 8th Ed.)
Nasopharyngeal cancer with tumor confined to the nasopharynx, or tumor extending to oropharynx and/or nasal cavity without parapharyngeal involvement. (from AJCC 8th Ed.)
Nasopharyngeal cancer with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles). (from AJCC 8th Ed.)
Nasopharyngeal cancer with tumor infiltrating bony structures at skull base, cervical vertebrae, pterygoid structures, and/or paranasal sinuses. (from AJCC 8th Ed.)
Nasopharyngeal cancer with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. (from AJCC 8th Ed.)
Nasopharyngeal cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Nasopharyngeal cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
A subjective score of 0 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 10 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 1 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 2 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 3 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 4 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 5 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 6 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 7 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 8 on a scale that ranges from 0: None to 10: The worst you can think of.
A subjective score of 9 on a scale that ranges from 0: None to 10: The worst you can think of.
The following anatomical structures define the neck lymph node boundary for level III: Superior: horizontal plane defined by the inferior body of the hyoid; inferior: horizontal plane defined by the inferior border of the cricoid cartilage; anterior (medial): lateral border of the sternohyoid muscle; posterior (lateral): lateral border of the sternocleidomastoid or sensory branches of the cervical plexus. (AJCC 8th ed.)
The following anatomical structures define the neck lymph node boundary for level IV: Superior: horizontal plane defined by the inferior border of the cricoid cartilage; inferior: clavicle; anterior (medial): lateral border of the sternohyoid muscle; posterior (lateral): lateral border of the sternocleidomastoid or sensory branches of the cervical plexus. (AJCC 8th ed.)
The following anatomical structures define the neck lymph node boundary for level VII: Superior: suprasternal notch; inferior: innominate artery; anterior (medial): sternum; posterior (lateral): trachea, esophagus, and prevertebral fascia. (AJCC 8th ed.)
The following anatomical structures define the neck lymph node boundary for level VI: Superior: hyoid bone; inferior: suprasternal notch; anterior (medial): common carotid artery; posterior (lateral): common carotid artery. (AJCC 8th ed.)
The anatomical structures that define the neck lymph node boundaries.
The following anatomical structures define the neck lymph node boundary for sublevel IA: Superior: symphysis of the mandible; inferior: body of the hyoid; anterior (medial): anterior belly of the contralateral digastric muscle; posterior (lateral): anterior belly of the ipsilateral digastric muscle. (AJCC 8th ed.)
The following anatomical structures define the neck lymph node boundary for sublevel IB: Superior: body of the mandible; inferior: posterior belly of the digastric muscle; anterior (medial): anterior belly of the digastric muscle; posterior (lateral): stylohyoid muscle. (AJCC 8th ed.)
The following anatomical structures define the neck lymph node boundary for sublevel IIA: Superior: skull base; inferior: horizontal plane defined by the inferior border of the hyoid bone; anterior (medial): stylohyoid muscle; posterior (lateral): vertical plane defined by the spinal accessory nerve. (AJCC 8th ed.)
The following anatomical structures define the neck lymph node boundary for sublevel IIB: Superior: skull base; inferior: horizontal plane defined by the inferior body of the hyoid bone; anterior (medial): vertical plane defined by the spinal accessory nerve; posterior (lateral): lateral border of the sternocleidomastoid muscle. (AJCC 8th ed.)
The following anatomical structures define the neck lymph node boundary for sublevel VA: Superior: apex of the convergence of the sternocleidomastoid and trapezius muscles; inferior: horizontal plane defined by the lower border of the cricoid cartilage; anterior (medial): posterior border of the sternocleidomastoid muscle or sensory branches of the cervical plexus; posterior (lateral): anterior border of the trapezius muscle. (AJCC 8th ed.)
The following anatomical structures define the neck lymph node boundary for sublevel VB: Superior: horizontal plane defined by the lower border of the cricoid cartilage; inferior: clavicle; anterior (medial): posterior border of the sternocleidomastoid muscle; posterior (lateral): anterior border of the trapezius muscle. (AJCC 8th ed.)
The implantation of tumor cells to surrounding tissue along the course of a contaminated instrument such as a biopsy needle or laparoscope.
A response indicating that an individual needs verbal or physical help or a carrying aid to use stairs.
A response indicating that an individual needs help with tasks related to eating, such as cutting food, spreading butter, etc.
A response indicating that an individual needs help with personal grooming care.
A response indicating that an individual needs some help but can do something alone.
A subjective response indicating that something is neither good nor bad.
A localized, pathological, or traumatic structural change, damage, deformity, or discontinuity of the bone that has not been previously seen or characterized.
A Chinese herbal medicine (CHM) composed of the dried root from the herbaceous plant Ox-Knee (Achyranthes bidentata Blume) belonging to the Amaranthaceae family. Niu Xi may regulate the blood, may help relieve certain pains, and it may tonify the liver and kidneys.
A response indicating that an individual did not have hearing problems.
The identification of a tumor or lesion located at or near the lymph node that is present at baseline, and is not the target of the therapeutic intervention.
The identification of a tumor or lesion that has a well-defined area of unequivocally increased signal intensity on MRI or CT scan images compared with the normal-appearing surrounding tissues, and is not the target of the therapeutic intervention.
The identification of a tumor or lesion without a well-defined area of unequivocally increased signal intensity on MRI or CT scan images compared with the normal-appearing surrounding tissues, and is not the target of the therapeutic intervention.
An area of the body subjected to inconsistent sun exposure.
Nutritional rickets due to dietary deficiency of calcium.
Hypophosphatemic rickets due to insufficient dietary phosphate intake or absorption.
Rickets due to dietary deficiency of calcium, phosphate, or vitamin D.
A response indicating that an individual has urinary accidents, but no more than once per 24 hours.
A response indicating occasional agreement.
An ependymal tumor affecting the occipital and parietal lobes and a brain ventricle.
A preparation containing plant-derived polyphenolic bioflavonoids composed of multimers (dimers, trimers, or higher order polymers) of the flavan-3-ol-based monomers catechin and epicatechin, which are extracted from sources rich in these chemicals, such as grape seeds, grape skin and pine bark, with potential anti-oxidant, anti-inflammatory, anti-microbial, anti-cancer and protective activities. Upon oral administration of oligomeric procyanidin complex (OPC), the polyphenols exert anti-oxidant activity by scavenging free radicals, which prevents both the formation of reactive oxygen species (ROS), particularly nitrous oxide (NO), and DNA damage. OPC also inhibits chemical-induced lipid peroxidation. In addition, OPC reduces the production advanced glycation end-products (AGE), decreases AGE accumulation in tissues, and inhibits the progression of AGE/receptor for AGE (RAGE)-mediated inflammatory transduction pathways, which inhibits the activation of pro-inflammatory transcriptional regulators and prevents the secretion of pro-inflammatory cytokines/chemokines. This ultimately prevents inflammatory-driven damage to end organs and may reduce inflammation-induced cancer formation and progression. In addition, OPC inhibits the activity of a variety of enzymes, including xanthine oxidase, collagenase, elastase hyaluronidase and beta-glucuronidase.
The lactate form of onalespib, a synthetic, orally bioavailable, small-molecule inhibitor of heat shock protein 90 (Hsp90) with potential antineoplastic activity. Onalespib selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability and degradation of many oncogenic signaling proteins.
A response indicating that an individual is only able to do an activity with help.
An oral proprietary P-glycoprotein (P-gp) pump inhibitor-based formulation containing the taxane docetaxel, a semisynthetic analogue of paclitaxel, and a P-gp pump inhibitor, with potential antineoplastic activity. Upon administration of oral docetaxel, the P-gp pump inhibitor moiety, which is not absorbed, binds to the P-gp pump in the gastrointestinal (GI) tract and prevents the P-gp pump-mediated efflux of docetaxel from cells the docetaxel has been internalized by back into the GI tract. This decreases P-gp-mediated excretion and enhances absorption of docetaxel. Upon absorption, docetaxel binds specifically to the beta-tubulin subunit of the microtubule, stabilizes tubulin and inhibits microtubule disassembly, which results in cell-cycle arrest at the G2/M phase and cell death. The P-gp pump inhibitor enhances the bioavailability of certain poorly bioavailable agents and thereby allows oral administration of those agents. P-gp, an efflux membrane transporter, plays a key role in active drug export, and prevents cellular uptake and accumulation of certain substances.
A morphologic finding of dysplastic epithelial cells in the oral cavity.
A clinical finding about one or more characteristics of oropharyngeal (p16-negative) cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of oropharyngeal (p16-negative) cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A clinical finding about one or more characteristics of p16-negative oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of oropharyngeal (p16-negative) cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of p16-negative oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of oropharyngeal (p16-negative) cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of p16-negative oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of p16-negative oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to p16-negative squamous cell carcinomas of the oropharynx, oropharyngeal cancers without p16 immunostaining performed, minor salivary gland carcinomas of the oropharynx, and neuroendocrine carcinomas of the oropharynx. Oropharyngeal cancers which are p16-positive are staged according to the classification for p16-positive oropharyngeal cancers. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with distant metastasis. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (-). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in any node(s) and clinically overt ENE(+). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in any node(s) and clinically overt ENE(+). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes any with ENE(+). (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with tumor 2 cm or smaller in greatest dimension. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with tumor larger than 2 cm but not larger than 4 cm in greatest dimension. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with moderately advanced or very advanced local disease. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Oropharyngeal (p16-negative) cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
A term that refers to the staging of p16-negative oropharyngeal carcinoma according to the American Joint Committee on Cancer, 8th edition.
A finding about one or more characteristics of p16-negative oropharyngeal and hypopharyngeal cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to p16-negative squamous cell carcinomas of the oropharynx, oropharyngeal cancers without p16 immunostaining performed, and all cancers of the hypopharynx. Minor salivary gland cancers and neuroendocrine carcinomas of the oropharynx and hypopharynx are included in this classification. Oropharyngeal cancers which are p16-positive are staged according to the classification for p16-positive oropharyngeal cancers. (from AJCC 8th Ed.)
An orally bioavailable inhibitor of both steroid 11beta-hydroxylase (cytochrome P450 (CYP) 11B1) and aldosterone synthase (CYP11B2; steroid 18-hydroxylase), with potential anti-adrenal activity and ability to treat Cushing disease (CD). Upon administration, osilodrostat binds to and inhibits the activity of CYP11B1, the enzyme that catalyzes the final step of cortisol synthesis from the precursor 11-deoxycortisol, and CYP11B2, the enzyme that catalyzes aldosterone synthesis from corticosterone and 11-deoxycorticosterone in the adrenal gland. The inhibition of CYP11B1 prevents the production of excess cortisol, thereby decreasing and normalizing the levels of cortisol. CD is most often caused by an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor.
A form of osteopetrosis in which osteoclasts are abundant but have severely impaired resorptive function.
An orally bioavailable oxidative phosphorylation (OxPhos) inhibitor, with potential antineoplastic activity. Upon administration of the OxPhos inhibitor IACS-010759, this agent binds to and inhibits complex I of the electron transport chain (NADH ubiquinone oxidoreductase), thereby selectively depriving tumor cells of nutrients, and energy, and inhibiting nucleotide and amino acid production, which induces autophagy, causes tumor cell death and inhibits cell proliferation. Mitochondrial complex I, which is hyperactivated in cancer cells to meet their increased demands for energy, plays a key role in the promotion of cancer cell proliferation.
An orally bioavailable small molecule inhibitor of the immune checkpoint regulatory proteins programmed cell death ligand-1 (PD-L1; B7-H1; CD274), PD-L2, and V-domain immunoglobulin (Ig) suppressor of T-cell activation (VISTA; programmed death 1 homolog; PD1H; PD-1H), with potential negative immune checkpoint regulatory and antineoplastic activities. Upon oral administration, PD-L1/PD-L2/VISTA antagonist CA-170 targets and binds to PD-L1, PD-L2 and VISTA. This inhibits PD-L1/PD-L2/VISTA-mediated signaling, abrogates the PD-L1-, PD-L2- and VISTA-induced suppression of T-lymphocyte immune responses, enhances cytotoxic T-cell proliferation and activation against tumor cells, increases cytokine production by T-cells, and inhibits tumor cell growth. PD-L1, PD-L2 and VISTA, negative checkpoint molecules of immune activation, play key roles in the suppression of T-cell functions.
A molecular genetic abnormality indicating the presence of multiple copies of the PDGFRB gene.
An orally available inhibitor of phosphatidylinositol 3-kinase (PI3K), with potential antineoplastic activity. PI3K inhibitor GDC0077 binds to and inhibits various members of the PI3K family, including activating mutations in the catalytic alpha isoform PIK3CA. PI3K inhibition prevents the activation of the PI3K-mediated signaling pathway and results in the inhibition of growth and survival of PI3K-overexpressing tumor cells. Dysregulation of the PI3K signaling pathway is frequently associated with tumorigenesis and tumor resistance to a variety of antineoplastic agents and radiotherapy. PIK3CA, which encodes the p110-alpha catalytic subunit of the class I PI3K, is frequently mutated in a variety of cancer cell types and plays a key role in cancer cell growth and invasion.
A molecular genetic abnormality indicating the presence of multiple copies of the PIK3C2B gene.
A change in the nucleotide sequence of the PIK3R1 gene.
A missense mutation in the POLE gene located in the region that encodes the exonuclease domain of the DNA polymerase epsilon catalytic subunit A protein (POLE protein). These mutations lead to defective DNA proof-reading by POLE protein during DNA replication and have been reported in patients with colorectal carcinoma and certain subtypes of endometrial carcinoma.
A change in the nucleotide sequence of the POLE gene.
A change in the nucleotide sequence of the PRKAR1A gene.
A change in the nucleotide sequence of the PRKDC gene.
A radioconjugate composed of the phosphoramidate agent CTT1057, a human prostate specific membrane antigen (PSMA) inhibitor, and labeled with the radioisotope fluorine F 18, with potential use as a tracer for PSMA-expressing tumors during positron emission tomography (PET). Upon intravenous administration of PSMA-targeted PET imaging agent fluorine F 18 CTT-1057, the CTT-1057 moiety targets and irreversibly binds to the extracellular domain of PSMA-expressing tumor cells. Upon rapid internalization, and following PET imaging, PSMA-expressing tumor cells can be detected. PSMA, a tumor-associated antigen (TAA) and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells.
An orally available pan-inhibitor of mutant forms of the metabolic enzyme isocitrate dehydrogenase type 1 (IDH1; IDH-1; IDH1 [NADP+] soluble), including forms with mutations of arginine 132 (IDH1(R132)), with potential antineoplastic activity. Upon administration, pan-mutant-IDH-1 inhibitor BAY-1436032 specifically inhibits the activity of IDH1 mutant forms, which prevents the formation of the oncometabolite 2-hydroxyglutarate (2HG) from alpha-ketoglutarate (a-KG). This prevents 2HG-mediated signaling and leads to both an induction of cellular differentiation and an inhibition of cellular proliferation in tumor cells expressing IDH1 mutant forms. IDH1 mutations, including IDH1(R132) mutations, are highly expressed in certain malignancies; they initiate and drive cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG.
A response indicating that a parent did not come to a clinic and that a mailed form was not returned.
A response indicating that a form was given to a parent, but that it was not returned.
A response indicating that a parent wishes to withdraw from further participation.
A response indicating that a parent or guardian did not speak English.
An ependymal tumor affecting the parietal lobe of the brain.
An ependymal tumor affecting the parietal and occipital lobes of the brain.
A response indicating that an individual has not had fatigue or lack of energy in the past 30 days.
A response indicating that an individual has not had a partner in the past 30 days.
Stage I includes: (T0, N0, M0); (T0, N1, M0); (T1, N0, M0); (T1, N1, M0); (T2, N0, M0); (T2, N1, M0). T0: No primary identified. T1: Tumor 2 cm or smaller in greatest dimension. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Tumor with metastasis in four or fewer lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T0, N2, M0); (T1, N2, M0); (T2, N2, M0); (T3, N0, M0); (T3, N1, M0); (T4, N0, M0); (T4, N1, M0). T0: No primary identified. T1: Tumor 2 cm or smaller in greatest dimension. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. T3: Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. T4: Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible or beyond. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx. N0: No regional lymph node metastasis. N1: Tumor with metastasis in four or fewer lymph nodes. N2: Tumor with metastasis in more than four lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N2, M0); (T4, N2, M0). T3: Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. T4: Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible or beyond. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx. N2: Tumor with metastasis in more than four lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
A response indicating that a patient was too ill to complete a form at this assessment.
A pegylated liposomal mitoxantrone formulation composed of the hydrochloride salt form of the anthracenedione antibiotic mitoxantrone encapsulated within pegylated small unilamellar vesicles (SUVs), with potential antineoplastic activity. Upon intravenous administration, mitoxantrone intercalates into and forms crosslinks with DNA, thereby disrupting DNA and RNA replication. This agent also binds to topoisomerase II, which both results in DNA strand breaks and prevents DNA synthesis. This leads to the induction of apoptosis in rapidly dividing cancer cells. The pegylated liposomal formulation improves drug penetration into tumors and decreases drug clearance, thereby increasing drug circulation and therapeutic efficacy while lowering toxic effects.
A subjective score of 0% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 10% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 20% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 30% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 40% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 50% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 60% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 70% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 80% on a scale that ranges from 0%: None to 100%: All of my food.
A subjective score of 90% on a scale that ranges from 0%: None to 100%: All of my food.
Transient hyperinsulinism that occurs in response to neonatal stress resulting in prolonged neonatal hypoglycemia, which is distinct from transitional hypoglycemia of typical infants.
A morphologic finding indicating the continuing presence of neuroblastic cells in a set of tissue samples collected over time.
A synthetic peptide-based, personalized cancer vaccine consisting of patient-specific mutated peptide epitopes, which are immunogenic and unique to the patient's tumor, with potential immunomodulating and antineoplastic activities. Vaccination with the neoantigen-based anti-cancer vaccine NEO-PV-01 stimulates the host immune system to mount a specific and potent cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis.
A finding about one or more characteristics of pharyngeal cancer, following the rules of the TNM AJCC v8 classification system. (from AJCC 8th Ed.)
A term that refers to the staging of pharyngeal carcinoma according to the American Joint Committee on Cancer, 8th edition.
A coagulation disorder characterized by the partial or complete absence of plasma-type kallikrein activity in the blood.
The transfer of multiple ADP-ribose molecules to amino acids within target proteins.
An ependymal tumor affecting the posterior cranial fossa.
The main language that is spoken by the subject most frequently or dominantly.
A subtype of micronodular adrenal hyperplasia, characterized by multiple pigmented nodules, which may occur in isolation or as part of the Carney complex.
A recombinant antibody prodrug composed of a monoclonal antibody directed against the tumor-associated antigen (TAA) programmed cell death 1 ligand 1 (PD-L1; B7-H1; CD274) that is linked to a proprietary masking peptide through a protease-cleavable linker on the amino terminus of the light chain domain of the antibody, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the linkage system is stable in the circulation and, upon extravasation into the tumor microenvironment, the peptide mask is cleaved by tumor-associated proteases. These proteases are present in high concentrations and aberrantly activated in the tumor microenvironment, while expressed as inactive forms, at much lower concentrations, in normal, healthy tissue. Protease cleavage of the linker enables binding of the unmasked, fully active monoclonal antibody moiety of CX-072 to PD-L1, which is over expressed on certain cancer cells. This blocks the binding to and activation of its receptor programmed cell death 1 (PD-1) on T-lymphocytes, thereby enhancing the T-cell-mediated anti-tumor immune response and reversing PD-L1/PD-1-mediated T-cell suppression. PD-L1 binding to PD-1 on T-cells suppresses the immune system and results in immune evasion. Compared to the unmodified PD-L1 antibody, peptide masking of CX-072 minimizes binding to PD-L1 in normal tissues, thereby decreasing autoimmune-based side effects while retaining anti-tumor activity.
An orally bioavailable androgen receptor (AR) antagonist with potential antineoplastic activity. Upon oral administration, proxalutamide binds to AR in target tissues, inhibits androgen-induced receptor activation, and facilitates the formation of inactive complexes that cannot translocate to the nucleus. This prevents binding to and transcription of AR-responsive genes that regulate prostate cancer cell proliferation. In addition, proxalutamide induces AR downregulation, thereby further preventing AR-mediated signaling. This ultimately leads to an inhibition of growth in AR-expressing prostate cancer cells. AR is overexpressed in prostate cancer and plays a key role in prostate cancer cell proliferation.
A marked decrease in contrast enhancement that is not due to actual tumor shrinkage, but that may be due to anti-angiogenic therapy or an increase in steroid dosage.
A change in the nucleotide sequence of the RAD50 gene.
A change in the nucleotide sequence of the RAD51 gene.
A change in the nucleotide sequence of the RAD51B gene.
A change in the nucleotide sequence of the RAD51C gene.
A change in the nucleotide sequence of the RAD51D gene.
A change in the nucleotide sequence of the RAD54L gene.
A change in the nucleotide sequence in a RAS family gene (HRAS, KRAS or NRAS).
An orally bioavailable selective inhibitor of mutant forms of and fusion products involving the proto-oncogene receptor tyrosine kinase RET, with potential antineoplastic activity. Upon administration, BLU-667 binds to and targets various RET mutants and RET-containing fusion product. RET gene mutations and translocations result in the upregulation and/or activation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a key role in the development and regression of these cancers.
An orally bioavailable agonist of retinoic acid-related orphan receptor gamma (RORg), with potential immunomodulatory and antineoplastic activities. Upon oral administration of RORg agonist LYC-55716, this agent selectively binds to the nuclear receptor transcription factor RORg, forming a receptor complex that translocates to the nucleus, and binds to ROR response elements (ROREs), enhancing the function, proliferation and survival of type 17 T-cells, including Th17 (helper T-cells) and Tc17 (cytotoxic T-cells). This may increase the expression of co-stimulatory molecules and decrease the expression of co-inhibitory molecules on T-cells leading to increased production of cytokines and chemokines by T-cells, decreased proliferation of regulatory T-cells (Tregs), and abrogation of tumor-induced immunosuppression. This ultimately induces a T-cell-mediated immune response against cancer cells and leads to a reduction in tumor cell growth. RORg, the nuclear receptor transcription factor that is involved in Th17/Tc17 differentiation, plays a key role in immune activation.
A change in the nucleotide sequence of the ROS1 gene.
A molecular abnormality indicating rearrangement of the ROS1 gene.
A cytogenetic abnormality that refers to any translocation involving the ROS1 gene.
A change in the nucleotide sequence of the RPA1 gene.
A benign or malignant neoplasm that affects the pituitary gland of a rat.
A subjective response indicating that something is rather poor.
A recombinant form of human bone morphogenetic protein 4 (rhBMP4; rhBMP-4), with potential antineoplastic activity. Upon administration, rhBMP4 binds to BMP receptors (BMPRs) and activates BMP-mediated signal transduction pathways. This may lead to the transcription of BMP4-target genes and to inhibition of the proliferation of certain tumor cell types. Additionally, rhBMP4 binding promotes the differentiation of normal stem cells and decreases both differentiation and renewal of cancer stem cells (CSCs). BMP4, an extracellular signaling molecule belonging to the transforming growth factor beta (TGFb) superfamily, plays a key role in bone formation. It also plays a role in the pathogenesis of certain cancers; BMP4 suppresses growth of certain types of cancer cells, and is also able to induce migration, invasion, and epithelial-mesenchymal transition (EMT), which may promote cancer metastasis and progression.
The reemergence of T acute lymphoblastic leukemia in childhood after a period of remission.
The reemergence of chronic lymphocytic leukemia/small lymphocytic lymphoma after a period of remission.
The reemergence of endometrial serous adenocarcinoma after a period of remission.
The reemergence of an ependymal tumor after a period of remission.
The reemergence of a malignant germ cell tumor after a period of remission.
The reemergence of a glioma after a period of remission.
The reemergence of gliosarcoma after a period of remission.
The reemergence of a primary malignant neoplasm after a period of remission.
The reemergence of a malignant neoplasm other than the original one, after a period of remission.
Squamous cell carcinoma of the head and neck which is amendable to surgical removal.
A response indicating that an individual was not bothered by or ringing or other noises.
A response indicating that ringing or other noises did not interfere with an individual's activities.
A response indicating that ringing or other noises did not make it hard for an individual to fall asleep.
A response indicating that ringing or other noises did not make it hard for an individual to pay attention.
A response indicating that ringing or other noises did not wake an individual from sleep.
An orally bioavailable capsule formulation containing the antipsychotic agent risperidone suspended in the lipid rumenic acid, with potential antineoplastic activity. Upon administration of VAL401, risperidone may, through an as of yet not elucidated mechanism of action, reduce cellular activity and tumor cell proliferation in multiple cancers.
A central nervous system neoplasm mostly occurring in the fourth ventricle region. It is characterized by the presence of neurocytes forming pseudorosettes and astrocytes which contain Rosenthal fibers. Cytologic atypia is minimal.
A Chinese herbal medicine (CHM) derived from the stems of the herbaceous plant Cistanche deserticola Y. C. Ma (Ginseng of the desert) belonging to the Orobanchaceae family. Rou Cong Rong may have antioxidative and neuroprotective activities. This traditional Chinese medicine (TCM) is used to help with pain, deficiency of kidney yang and may relieve constipation by moistening and smoothing stool.
A miniaturized drug conjugate composed of a peptide analog of somatostatin that targets the somatostatin receptor 2 (SSTR2) and is conjugated, through a cleavable linker, to the microtubule-binding cytotoxic maytansinoid DM1 (mertansine), with potential anti-tumor activity. Upon administration, the peptide ligand moiety of PEN-221 targets and binds to SSTR2, which is overexpressed on certain tumor cell types. Binding stimulates SSTR2-mediated endocytosis of the agent; upon internalization, the DM1 moiety is released and binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics. This inhibits both cell division and the proliferation of SSTR2-expressing cancer cells. Compared to antibody-drug conjugates (ADCs), miniaturized drug conjugates are much smaller and can more easily penetrate and distribute in dense tumor tissue.
: A synthetic cyclic dinucleotide (CDN) and agonist of stimulator of interferon genes protein (STING), with potential immunoactivating and antineoplastic activities. Upon intratumoral (IT) administration, STING agonist MK-1454 binds to STING and activates the STING pathway, which promotes IKK-related kinase TANK-binding kinase 1 (TBK1) signaling and activates nuclear factor-kappa B (NF-kB) and interferon regulatory factor 3 (IRF3) in immune cells in the tumor microenvironment; this leads to the production of pro-inflammatory cytokines, including interferons (IFNs). Specifically, expression of IFN-beta (IFNb) enhances the cross-presentation of tumor-associated antigens by CD8alpha-positive and CD103-positive dendritic cells (DCs) to cytotoxic T-lymphocytes (CTLs). This results in a CTL-mediated immune response against tumor cells and causes tumor cell lysis.
Diabetes mellitus caused by activating mutation(s) in the ABCC8 gene, encoding the sulfonylurea receptor 1 (SUR1) subunit of the pancreatic beta cell adenosine triphosphate-sensitive potassium channel. Note: Inactivating mutation(s) in the ABCC8 gene result in hyperinsulinism.
A rare slow-growing malignant bone tumor arising from the sacral area. It is characterized by a lobulated growth pattern, myxoid stroma formation, and the presence of physaliphorous cells.
A classic form of congenital adrenal hyperplasia characterized by complete absence of 21-hydroxylase activity resulting in deficiency of glucocorticoids and mineralocorticoids accompanied by androgen excess causing virilization in female infants. Mineralocorticoid deficiency results in renal salt-wasting, and if untreated, hyponatremia, hyperkalemia, and shock.
A humanized monoclonal antibody directed against the human immunosuppressive molecule CD200 (OX-2) with potential immunomodulating and antineoplastic activities. Samalizumab binds to CD200, blocking the binding of CD200 to its receptor, CD200R, present on cells of the macrophage lineage; inhibition of CD200 may augment the cytotoxic T-lymphocyte (CTL) mediated immune response against CD200-expressing tumor cells. CD200 is a type 1a transmembrane protein, related to the B7 family of co-stimulatory receptors, and is upregulated on the surface of multiple hematologic malignant cells; this transmembrane protein appears to be involved in the downregulation of a Th1 (helper T cell) immune response.
Additional language(s) that is spoken by the subject but which is not considered the primary language.
Parathyroid hormone (PTH) resistance caused by vitamin D deficiency and characterized by clinically increased PTH concentrations with relative hyperphosphatemia. The diagnosis can be confirmed by finding of a normal cyclic adenosine monophosphate (cAMP) response to PTH infusion, but deficient phosphaturic response, indicating a defect distal to cAMP generation in renal cells.
An orally available non-steroidal, lyase-selective inhibitor of the steroid 17-alpha-hydroxylase/C17,20 lyase (CYP17A1 or CYP17), with potential anti-androgenic and antineoplastic activities. Upon oral administration, seviteronel selectively inhibits the enzymatic activity of the cytochrome P450 C17,20 lyase in both the testes and adrenal glands, thereby inhibiting androgen production. This may decrease androgen-dependent growth signaling and may inhibit cell proliferation of androgen-dependent tumor cells. The cytochrome P450 enzyme CYP17A1, localized to the endoplasmic reticulum, exhibits both 17alpha-hydroxylase and 17,20-lyase activities; it plays a key role in the steroidogenic pathway. The lyase-selective activity of seviteronel prevents the increased synthesis of mineralocorticoids that is normally seen with non-selective CYP17 inhibitors, which also inhibit the 17-alpha-hydroxylase activity of CYP17A1.
A Chinese herbal medicine (CHM) containing the cooked or steamed root of the herbaceous plant Rehmannia glutinosa Libosch of the Scrophulariaceae family. Shu Di Huang is believed to treat deficiency of yin and body fluid by nourishing yin. It may tonify and nourish blood.
An autosomal dominant condition usually caused by mutation(s) in the SHH gene, encoding sonic hedgehog, a secreted protein involved in the organization and morphology of the developing embryo. This condition is characterized by multiple, mainly midline, developmental variations, including the presence of a tooth in the center of the maxillary dental arch in both primary and permanent dentition, and any combination of the following: holoprosencephaly, congenital nasal malformation (choanal atresia, midnasal stenosis, or congenital pyriform aperture stenosis), cleft lip and/or palate, hypopituitarism (including hypothyroidism and hypogonadism, resulting in variations in genital development including small penis or incomplete masculinization in male infants), congenital heart anomalies, and developmental delay.
An adenocarcinoma composed of small malignant cells.
An extramedullary myeloid tumor that arises from the small intestine. It often presents with abdominal pain and obstruction.
A dietary supplement containing sodium nitrate, that can be used for nitrate supplementation purposes. Upon oral administration, nitrate is absorbed by the body and is partially converted to nitrite, which is stored and circulated in the blood, leading to an increase in nitrite levels. Nitrate, and to some extent nitrite, accumulates in saliva and may enhance salivary flow, which may help to treat dry mouth and chemo- and radiation-induced oropharyngeal problems.
An evaluation of the soft tissue response of the disease to the therapy.
An orally bioavailable inhibitor of the splicing factor 3B subunit 1 (SF3B1), with potential antineoplastic activity. Upon administration, H3B-8800 binds to and blocks the activity of SF3B1, a core spliceosome protein that is mutated in various cancer cells. This modulates RNA splicing by preventing aberrant mRNA splicing by the spliceosome, blocks RNA mis-splicing, enhances proper RNA splicing and prevents the expression of certain tumor-associated genes. This leads to an induction of apoptosis and prevents tumor cell proliferation. In many cancer cells, core spliceosome proteins, including SF3B1, U2 small nuclear ribonucleoprotein auxiliary factor 1 (U2AF1), serine/arginine-rich splicing factor 2 (SRSF2) and U2 small nuclear ribonucleoprotein auxiliary factor subunit-related protein 2 (ZRSR2), are mutated and aberrantly activated leading to a dysregulation of mRNA splicing.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor limited to one subsite of hypopharynx and/or 2 cm or smaller in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor size 2 cm or less in greatest dimension and 5 mm or less depth of invasion (DOI). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor measuring 2 cm or less in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor confined to the nasopharynx, or tumor extending to oropharynx and/or nasal cavity without parapharyngeal involvement. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor 2 cm or smaller in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Tumor invading more than one subsite of hypopharynx or an adjacent site, or measuring more than 2 cm but not more than 4 cm in greatest dimension without fixation of hemilarynx. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Tumor size 2 cm or less in greatest dimension, DOI greater than 5 mm and equal or less than 10 mm or tumor greater than 2 cm but 4 cm or less in greatest dimension and 10 mm or less DOI. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Tumor measuring more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T1, N1, M0); (T0, N1, M0); (T2, N0, M0); (T2, N1, M0). T1: Tumor confined to the nasopharynx, or tumor extending to oropharynx and/or nasal cavity without parapharyngeal involvement. T0: No tumor identified, but EBV-positive cervical node(s) involvement is present. T2: Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles). N0: No regional lymph node metastasis. N1: Tumor with unilateral metastasis in cervical lymph node(s), and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor larger than 4 cm in greatest dimension or with fixation of hemilarynx or extension to esophagus. T1: Tumor limited to one subsite of hypopharynx and/or 2 cm or smaller in greatest dimension. T2: Tumor invading more than one subsite of hypopharynx or an adjacent site, or measuring more than 2 cm but not more than 4 cm in greatest dimension without fixation of hemilarynx. N0: No regional lymph node metastasis. N1: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (-). M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor size greater than 4 cm or any tumor greater than 10 mm DOI. T1: Tumor size 2 cm or less in greatest dimension and 5 mm or less DOI. T2: Tumor size 2 cm or less in greatest dimension, DOI greater than 5 mm and equal or less than 10 mm or tumor greater than 2 cm but 4 cm or less in greatest dimension and 10 mm or less DOI N1: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (extranodal extension)(-). M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: (T3, N0, M0); (T0, N1, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor measuring more than 4 cm in greatest dimension, and/or tumor having extraparenchymal extension. T0: No evidence of primary tumor. T1: Tumor measuring 2 cm or less in greatest dimension without extraparenchymal extension. T2: Tumor measuring more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T1, N2, M0); (T0, N2, M0); (T2, N2, M0); (T3, N0, M0); (T3, N1, M0); (T3, N2, M0). T1: Tumor confined to the nasopharynx, or tumor extending to oropharynx and/or nasal cavity without parapharyngeal involvement. T0: No tumor identified, but EBV-positive cervical node(s) involvement is present. T2: Tumor with extension to parapharyngeal space, and/or adjacent soft tissue involvement (medial pterygoid, lateral pterygoid, prevertebral muscles). T3: Tumor infiltrating bony structures at skull base, cervical vertebrae, pterygoid structures, and/or paranasal sinuses. N0: No regional lymph node metastasis. N1: Tumor with unilateral metastasis in cervical lymph node(s), and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. N2: Tumor with bilateral metastasis in cervical lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. T1: Tumor 2 cm or smaller in greatest dimension. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (-). M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: T0, N1, M0. T0: No evidence of primary tumor. N1: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (extranodal extension)(-). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (Any T, N3, M0); (T4b, Any N, M0); IVC: (Any T, Any N, M1). T4a: Moderately advanced local disease. Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue. Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. T1: Tumor limited to one subsite of hypopharynx and/or 2 cm or smaller in greatest dimension. T2: Tumor invading more than one subsite of hypopharynx or an adjacent site, or measuring more than 2 cm but not more than 4 cm in greatest dimension without fixation of hemilarynx. T3: Tumor larger than 4 cm in greatest dimension or with fixation of hemilarynx or extension to esophagus. T4b: Very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. N0: No regional lymph node metastasis. N1: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (-). N2: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). N3: Tumor with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes any with ENE(+). M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB (Any T, N3, M0); (T4b, Any N, M0); IVC (Any T, Any N, M1). T4a (lip): Tumor invades through cortical bone or involves the inferior alveolar nerve, floor of mouth, or skin of face (i.e., chin or nose). T4a (oral cavity): Tumor invades adjacent structures only (e.g., through cortical bone of the mandible or maxilla, or involves the maxillary sinus or skin of face). Note: Superficial erosion of bone/tooth socket (alone) by a gingival primary is not sufficient to classify a tumor as T4. T1: Tumor size 2 cm or less in greatest dimension and 5 mm or less DOI. T2: Tumor size 2 cm or less in greatest dimension, DOI greater than 5 mm and equal or less than 10 mm or tumor greater than 2 cm but 4 cm or less in greatest dimension and 10 mm or less DOI. T3: Tumor size greater than 4 cm or any tumor greater than 10 mm DOI. T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases the internal carotid artery. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(-). N2: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE (-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, ENE(-). N3: Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE (-); or in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral or bilateral lymph nodes any with ENE(+). M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th Ed.)
Stage IV includes: IVA: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0); (Any T, N3, M0); IVB (Any T, Any N, M1). T4: Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. N0: No regional lymph node metastasis. N1: Tumor with unilateral metastasis in cervical lymph node(s), and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. N2: Tumor with bilateral metastasis in cervical lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. N3: Tumor with unilateral or bilateral metastasis in cervical lymph node(s), larger than 6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (Any T, N3, M0); (T4b, Any N, M0); IVC: (Any T, Any N, M1). T4a: Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx. T1: Tumor 2 cm or smaller in greatest dimension. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. T3: Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. T4b: Very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery. N0: No regional lymph node metastasis. N1: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (-). N2: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). N3: Tumor with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes any with ENE(+). M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Moderately advanced local disease. Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue. Central compartment soft tissue includes prelaryngeal strap muscles and subcutaneous fat. T1: Tumor limited to one subsite of hypopharynx and/or 2 cm or smaller in greatest dimension. T2: Tumor invading more than one subsite of hypopharynx or an adjacent site, or measuring more than 2 cm but not more than 4 cm in greatest dimension without fixation of hemilarynx. T3: Tumor larger than 4 cm in greatest dimension or with fixation of hemilarynx or extension to esophagus. N0: No regional lymph node metastasis. N1: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(-). N2: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a (lip): Tumor invades through cortical bone or involves the inferior alveolar nerve, floor of mouth, or skin of face (i.e., chin or nose). T4a (oral cavity): Tumor invades adjacent structures only (e.g., through cortical bone of the mandible or maxilla, or involves the maxillary sinus or skin of face). Note: Superficial erosion of bone/tooth socket (alone) by a gingival primary is not sufficient to classify a tumor as T4. T1: Tumor size 2 cm or less in greatest dimension and 5 mm or less DOI. T2: Tumor size 2 cm or less in greatest dimension, DOI greater than 5 mm and equal or less than 10 mm or tumor greater than 2 cm but 4 cm or less in greatest dimension and 10 mm or less DOI. T3: Tumor size greater than 4 cm or any tumor greater than 10 mm DOI. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(-). N2: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE (-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension, ENE(-). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T0, N2, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Moderately advanced disease. Tumor invades skin, mandible, ear canal, and/or facial nerve. T0: No evidence of primary tumor. T1: Tumor measuring 2 cm or less in greatest dimension without extraparenchymal extension. T2: Tumor measuring more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. T3: Tumor measuring more than 4 cm in greatest dimension, and/or tumor having extraparenchymal extension. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(+); or more than 3 cm but not more than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-), or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0); (Any T, N3, M0); T4: Tumor with intracranial extension, involvement of cranial nerves, hypopharynx, orbit, parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. N0: No regional lymph node metastasis. N1: Tumor with unilateral metastasis in cervical lymph node(s), and/or unilateral or bilateral metastasis in retropharyngeal lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. N2: Tumor with bilateral metastasis in cervical lymph node(s), 6 cm or smaller in greatest dimension, above the caudal border of cricoid cartilage. N3: Tumor with unilateral or bilateral metastasis in cervical lymph node(s), larger than 6 cm in greatest dimension, and/or extension below the caudal border of cricoid cartilage. M0: No distant metastasis. (AJCC 8th ed.)
Stage IVA includes: T0, N2, M0. T0: No evidence of primary tumor. N2: Metastasis in a single ipsilateral or contralateral cervical lymph node 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral cervical lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral cervical lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral cervical lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IVB includes: (Any T, N3, M0); (T4b, Any N, M0). T4b: Very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. N3: Tumor with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes any with ENE(+). M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: (Any T, N3, M0); (T4b, Any N, M0). T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases the internal carotid artery. N3: Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE (-); or in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral or bilateral lymph nodes any with ENE(+). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IVB includes: (T4b, Any N, M0); (Any T, N3, M0). T4b: Very advanced disease. Tumor invades skull base and/or pterygoid plates and/or encases carotid artery. N0: No regional lymph node metastasis. N3: Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or multiple ipsilateral, contralateral, or bilateral nodes any with ENE(+). M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVB includes: T0, N3, M0. T0: No evidence of primary tumor. N3: Metastasis in a cervical lymph node larger than 6 cm in greatest dimension and ENE(-); or metastases in a single ipsilateral cervical lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral cervical lymph nodes, any size and ENE(+) in any node. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IVC includes: Any T, Any N, M1. M1: distant metastasis. (AJCC 8th ed.)
Congenital lipoid adrenal hyperplasia (CLAH) due to loss-of-function mutations in the STAR gene, resulting in decreased or absent production of steroidogenic acute regulatory protein (StAR), which leads to deficient transport of cholesterol from the outer to the inner mitochondrial membrane.
An area of the body exposed to sunlight.
An ependymal tumor arising from the supratentorial region of the brain.
A sustained-release (SR) poloxamer hydrogel formulation containing the glucocorticoid dexamethasone (DXM), with potential otoprotective and anti-apoptotic activities. Prior to the administration of an ototoxic drug and upon intratympanic (IT) injection of the DXM sustained-exposure formulation OTO-104, DXM is slowly released from the hydrogel over time; DMX then binds to glucocorticoid nuclear receptors, and activates cell survival pathways. This prevents ototoxic drug-induced generation of reactive oxygen species (ROS) by activating anti-oxidant enzymes, blocking the activation of inflammatory cytokines and inducing stress signaling pathways, which ultimately prevents apoptosis of auditory hair cells in the inner ear compartment. This prevents or reduces drug-induced ototoxicity caused by certain therapeutic agents, such as platinum-based anticancer agents. This may reduce or prevent hearing loss, tinnitus, and vertigo. The SR formulation provides increased concentrations of DXM in the inner ear and maintains the elevated levels for a longer time without the need of the multiple IT injections needed when using non-SR DXM formulations. This agent also reduces the symptoms of certain ear-related disorders.
A therapeutic peptide vaccine consisting of two highly immunogenic synthetic long peptides (SLPs), which are 25-35 amino acids in size, derived from the human papillomavirus (HPV) type 16 oncoprotein E6, and conjugated to a proprietary toll-like receptor 2 (TLR2) ligand (TLR2-L) immunoadjuvant, with potential immunostimulating and antitumor activities. Upon administration, the TLR2-L moiety of the synthetic long E6 peptides TLR ligand conjugate vaccine targets and binds to TLRs expressed on antigen-presenting cells (APCs), particularly dendritic cells (DCs). This increases the direct targeting of, binding to, uptake by, and processing of the SLPs into small pieces by the DCs. The processed viral epitopes are presented by DCs, which activate and stimulate the host immune system to mount specific cytotoxic T-lymphocyte (CTL) and helper T (Th) cell responses against HPV E6-expressing tumor cells. This results in the destruction of tumor cells and leads to decreased growth of HPV E6-expressing tumor cells. The E6 oncoprotein is implicated in tumorigenesis in a variety of cancers. The TLR2-L improves antigen processing and presentation by, and activation of APCs, thereby improving the immunostimulatory effect of the vaccine. The two peptides cover the most immunodominant regions of the HPV16 E6 oncogenic protein and contain both Th and CTL epitopes.
An antiquated primary tumor finding term that refers to colorectal cancer which has spread by direct extension beyond the immediately adjacent organs or tissues. (AJCC 1st Ed.)
A change in the nucleotide sequence of the TERT gene.
An orally bioavailable agent that targets transforming growth factor-beta (TGFb), with potential antineoplastic activity. Upon administration, LY3200882 specifically targets and binds to TGFb, which prevents both the binding of TGFb to its receptor TGFbR and TGFb-mediated signal transduction. This may lead to a reduction in TGFb-dependent proliferation of cancer cells. The TGFb signaling pathway is often deregulated in tumors, and plays a key role in the regulation of cell growth, differentiation, apoptosis, motility, invasion, angiogenesis, and various immune responses.
A change in the nucleotide sequence of the TSHR gene.
Familial glucocorticoid deficiency caused by mutation(s) in the TXNRD2 gene encoding thioredoxin reductase 2.
A chromosomal aberration where the telomeric and subtelomeric regions of a chromosome does not have the expected 1:1 ratio for the alleles and telomeric sequences inherited from the two parental chromosomes.
An ependymal tumor affecting the temporal lobe of the brain.
An ependymal tumor affecting the temporal and parietal lobes of the brain.
An ependymal tumor affecting the temporal and parietal lobes, and a lateral ventricle of the brain.
A synthetic peptide vaccine, containing 16 amino acid residues (611-626) of the human telomerase reverse transcriptase catalytic subunit (hTERT), with potential antineoplastic activity. Telomerase, a reverse transcriptase normally repressed in healthy cells, is overexpressed in most cancer cells and plays a key role in cellular proliferation. Vaccination with tertomotide may activate the immune system to mount a cytotoxic T-lymphocyte (CTL) response against telomerase-expressing cells.
An indication that a test was not ordered.
An ependymal tumor arising from the third ventricle of the brain.
An ependymal tumor arising from the thoracic region of spinal cord.
An ependymal tumor affecting the spinal cord in the thoracic and lumbosacral regions.
A disorder characterized by the partial or complete absence of tissue-type kallikrein activity in the tissues and glandular secretions where it is normally present.
Any pharmaceutical formulation that contains agents used in traditional Chinese medicine (TCM).
Monogenic diabetes caused by inactivating mutation(s) in transcription factors regulating expression of pancreatic beta cell genes.
Hyperinsulinism that resolves spontaneously. This is the most common cause of neonatal hypoglycemia.
Primary hypothyroidism that resolves spontaneously.
A vascular-targeting agent composed of the extracellular domain of the trunctated form of issue factor (tTF) conjugated to the C-terminal peptide GNGRAHA (NGR), with potential procoagulatory and antineoplastic activities. Upon administration, the NGR peptide moiety of tTF-NGR targets and binds to the surface protein aminopeptidase N (CD13) expressed on endothelial cells in tumor vessels. Upon deamidation of the NGR peptide moiety, this agent also binds to integrin alphaVbeta3 (aVb3; CD51/CD61) in the tumor vasculature. In turn, the tTF causes occlusion of the tumor blood vessels, which causes an inhibition of blood supply and flow in the tumor, nutrition and induced tumor cell death and an inhibition of tumor cell proliferation. TF plays a key role in the coagulation cascade. NGR is a asparagine-glycine-arginine containing peptide and ligand of CD13. Both aVb3 and CD13 are surface proteins that are upregulated on endothelial cells of tumor vessels.
A subjective score of 1 on a scale that ranges from 1: yes, that is true to 5: no, that is not true.
A subjective score of 2 on a scale that ranges from 1: yes, that is true to 5: no, that is not true.
A subjective score of 3 on a scale that ranges from 1: yes, that is true to 5: no, that is not true.
A subjective score of 4 on a scale that ranges from 1: yes, that is true to 5: no, that is not true.
A subjective score of 5 on a scale that ranges from 1: yes, that is true to 5: no, that is not true.
An evaluation of the tumor marker response of the disease to the therapy.
An indication that an action, task, or function was not done due to a lack of skill, means, or opportunity.
A term that refers to the staging of unknown primary tumor (except for EBV-related and HPV-related tumors) and metastatic cervical adenopathy according to the American Joint Committee on Cancer, 8th edition.
A clinical finding about one or more characteristics of an unknown primary tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of cervical lymph nodes. It applies to patients who are treated with primary nonsurgical treatment without a cervical lymph node dissection. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of an unknown primary tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of cervical lymph nodes. It applies to patients who are treated surgically with a cervical lymph node dissection. (from AJCC 8th Ed.)
Unknown primary tumor with metastasis in a single ipsilateral cervical lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE (extranodal extension)(-); or metastases in multiple ipsilateral cervical lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral cervical lymph nodes, none larger than 6 cm in greatest dimension, ENE(-). (from AJCC 8th Ed.)
Unknown primary tumor with metastasis in a single ipsilateral cervical lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Unknown primary tumor with metastases in multiple ipsilateral cervical lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Unknown primary tumor with metastases in bilateral or contralateral cervical lymph nodes, none larger than 6 cm in greatest dimension, ENE(-). (from AJCC 8th Ed.)
Unknown primary tumor with metastasis in a cervical lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in any cervical node(s) with clinically overt ENE(+) (ENEc). ENEc is defined as invasion of skin, infiltration of musculature, dense tethering or fixation to adjacent structures, or cranial nerve, brachial plexus, sympathetic trunk, or phrenic nerve invasion with dysfunction. (from AJCC 8th Ed.)
Unknown primary tumor with metastasis in a cervical lymph node larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Unknown primary tumor with metastasis in any cervical node(s) with clinically overt ENE(+) (ENEc). ENEc is defined as invasion of skin, infiltration of musculature, dense tethering or fixation to adjacent structures, or cranial nerve, brachial plexus, sympathetic trunk, or phrenic nerve invasion with dysfunction. (from AJCC 8th Ed.)
Unknown primary tumor in which no regional lymph node metastases are detected. (from AJCC 8th Ed.)
Unknown primary tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE (extranodal extension)(-). (from AJCC 8th Ed.)
Unknown primary tumor with metastasis in a single ipsilateral or contralateral cervical lymph node 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral cervical lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral cervical lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral cervical lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). ENE detected on histopathologic examination is designated as ENEmi (microscopic ENE equal or less than 2 mm) or ENEma (major ENE more than 2 mm). (from AJCC 8th Ed.)
Unknown primary tumor with metastases in bilateral or contralateral cervical lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Unknown primary tumor with metastasis in a cervical lymph node larger than 6 cm in greatest dimension and ENE(-); or metastases in a single ipsilateral cervical lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral cervical lymph nodes, any size and ENE(+) in any node. (from AJCC 8th Ed.)
Unknown primary tumor with metastases in a single ipsilateral cervical lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral cervical lymph nodes, any size and ENE(+) in any node. (from AJCC 8th Ed.)
Unknown primary tumor in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
An adenocarcinoma that arises from the gastrointestinal system and is not amenable to surgical resection.
A Ewing sarcoma which is not amenable to surgical resection.
A leiomyosarcoma which is not amenable to surgical resection.
A liposarcoma which is not amenable to surgical resection.
An osteosarcoma which is not amenable to surgical resection.
A carcinoma that arises from the thyroid gland and is not amenable to surgical resection.
A transitional cell carcinoma which is not amenable to surgical resection.
A finding of rhabdomyosarcoma in adulthood that has not been treated.
A finding of chronic lymphocytic leukemia that has not been treated.
A finding of small cell carcinoma which has spread beyond one hemi-thorax and the regional lymph nodes and has not been treated.
A finding of small lymphocytic lymphoma that has not been treated.
A response indicating that an individual is or has been urinary continent for over 7 days.
A human, agonistic immunoglobulin (Ig) G2 monoclonal antibody (mAb) targeting 4-1BB (CD137, TNFRSF9), with potential immunostimulating activity. Upon administration, utomilumab binds to and activates 4-1BB expressed on various immune cells, such as CD8-positive and CD4-positive T cells and natural killer (NK) cells. This enhances 4-1BB-mediated signaling, induces cytokine production and promotes anti-tumor immune responses. 4-1BB, a member of the tumor necrosis factor (TNF)/nerve growth factor (NGF) family of receptors, plays an important role in the regulation of immune responses.
A topical ointment formulation containing a voltage-dependent anion channel (VDAC)/hexokinase 2 (HK2) modulator, with potential activity against certain skin cancers. Upon topical application, VDA-1102, as a protein-protein interaction (PPI) disrupter, allosterically binds to HK2, and causes HK2 to dissociate from VDAC, which prevents glycolysis and triggers apoptosis, thereby inhibiting tumor cell growth in VDAC/HK2-expressing tumor cells without affecting the surrounding healthy skin tissue. The VDAC/HK2 system, over-activated in cancer cells, plays a key role in tumor cell proliferation. The VDAC/HK2 association protects cancer cells from apoptosis. HK2 is overexpressed in many malignant cancer tissues that rely on glycolysis, while its expression is limited in normal healthy cells.
The presence of oxidized elements in cholesterol-bearing very low-density lipoprotein (VLDL) particles in the blood. Oxidation may be associated with increased risk for atherosclerosis.
A recombinant, replication competent form of the oncolytic RNA virus vesicular stomatitis virus (VSV), based on the Indiana strain of VSV, that is genetically engineered to express the genes for the human cytokine interferon beta (IFNbeta) and the human thyroidal sodium-iodide symporter (NIS), with potential oncolytic and imaging activities. Upon intravenous administration, VSV-hIFNbeta-NIS is preferentially taken up by tumor cells, resulting in tumor cell infection, viral replication and a direct virus-mediated cytolytic effect against the infected tumor cells. IFN-mediated signaling is defective in tumor cells and tumor cells are unable to exert an anti-viral response against VSV. As normal, healthy cells secrete and respond normally to IFNbeta and are able to activate IFN-mediated anti-viral pathways, the expressed IFNbeta from the VSV-infected tumor cells helps protect normal cells from VSV infection. Upon subsequent administration of certain isotope-containing imaging agents, NIS expression by the infected tumor cells allows visualization and tracking of VSV biodistribution, and analysis and quantification of VSV-infected tumor cells by positron emission tomography (PET). Also, upon subsequent administration of the radioisotope iodine I 131 (I131), I131 can be taken up by NIS and allows for a cytotoxic dose of radiation to accumulate in the NIS-expressing VSV-infected tumor cells, which also leads to tumor cell death.
A humanized bispecific immunoglobulin G (IgG1) monoclonal antibody targeting both the vascular endothelial growth factor receptor (VEGFR) ligand VEGF-A and the Tie2 receptor ligand angiopoietin-2 (Ang-2), with potential antineoplastic and anti-angiogenic activities. Upon administration of vanucizumab, the anti-VEGF-A arm, which is based on bevacizumab, targets and binds to VEGF-A and the anti-Ang2 arm, which is based on the anti-Ang-2 antibody LC06, targets and binds to Ang2, thereby simultaneously binding and neutralizing both VEGF-A and Ang2. This prevents the activation of both VEGF-A/VEGFR- and Ang2/Tie2-mediated signaling pathways. Altogether, this results in the inhibition of proliferation of VEGF-A- and/or Ang2-overexpressing tumor cells. VEGF-A and Ang2, both upregulated in a variety of tumor cell types, play key roles in tumor cell proliferation, angiogenesis and metastasis.
An ependymal tumor arising from a brain ventricle.
A finding indicating that a neoplasm affects exclusively a brain ventricle.
An ependymal tumor affecting a brain ventricle and the brain stem.
A response indicating a very high level of confidence.
A response indicating a very low level or an absence.
An autosomal recessive form of rickets caused by mutation(s) in the VDR gene, encoding the vitamin D receptor. The condition is characterized by hypocalcemia, increased concentrations of calcitriol, secondary hyperparathyroidism, early-onset rickets and alopecia.
An electrocardiographic finding of large QRS amplitudes that may indicate left ventricular hypertrophy, but is without any of the secondary findings that are typically seen with this diagnosis: left atrial enlargement, left axis deviation, or typical pattern of ST depression and T wave inversion.
A response indicating that an individual experiences or experienced something when walking on flat ground.
A response indicating that an individual can walk with verbal or physical help of one person.
A group of syndromes caused by autosomal dominant mutation(s) in the WT1 gene, encoding Wilms tumor protein.
A response indicating that an individual is able to do an activity without help but it is difficult.
Hypothyroidism induced by excessive levels of iodine in the blood.
A traditional Chinese medicine (TCM) based formulated may benefit Qi and Yin, and may help with the detoxification process.
A traditional Chinese medicine (TCM) based that may benefit Qi and Yin, and may help with the detoxification process.
A traditional Chinese medicine (TCM)-based formulation that may benefit Qi, and boost Yin.
A traditional Chinese medicine (TCM) based formulation consisting of milkvetch root, glehnia root, asparagus root, lilyturf root, grossy privet fruit, spikemoss herb, Chinese sage herb, and manyleaf paris rhizome, with potential immuno-enhancing, detoxifying and antineoplastic activities. Upon administration, yiqi-yangyin-jiedu decoction (YYJD) may activate the immune system by enhancing T-lymphocyte activity, and inhibiting tumor cell proliferation. YYJD may also ameliorate the qi-yin deficiency syndrome by strengthening qi and nourishing yin. YYJD may help remove toxic substance.
A zinc finger nuclease (ZFN) targeting the human papillomavirus (HPV) type 16 (HPV16) oncoprotein E7, with potential antineoplastic activity. Upon transfection of ZFN-603 into HPV16-positive cells, ZFN-603 targets, binds to and cleaves the HPV16 E7 oncogene in HPV16-infected cells. By cleaving the HPV16 E7 DNA, the E7 oncoprotein is not expressed. This results in an inhibition of E7-mediated signaling, an induction of apoptosis, and inhibition of tumor cell proliferation in HPV16-expressing cells. In addition, preventing E7 expression induces the expression of tumor suppressor genes, thereby further preventing HPV-induced cancer cell formation and proliferation. E7 plays a key role in promoting both viral infection and carcinogenesis. ZFN, an engineered endonuclease in which a DNA-binding zinc finger protein is fused to a DNA-cleavable domain, cleaves specific DNA sites.
A zinc finger nuclease (ZFN) targeting the human papillomavirus (HPV) type 18 (HPV18) oncoprotein E7, with potential antineoplastic activity. Upon transfection of ZFN-758 into HPV18-positive cells, ZFN-758 targets, binds to and cleaves the HPV18 E7 oncogene in HPV18-infected cells. By cleaving the HPV18 E7 DNA, the E7 oncoprotein is not expressed. This results in an inhibition of E7-mediated signaling, an induction of apoptosis, and an inhibition of tumor cell proliferation in HPV18-expressing cells. In addition, preventing E7 expression induces the expression of tumor suppressor genes, thereby further preventing HPV-induced cancer cell formation and proliferation. E7 plays a key role in promoting both viral infection and carcinogenesis. ZFN, an engineered endonuclease in which a DNA-binding zinc finger protein is fused to a DNA-cleavable domain, cleaves specific DNA sites.
An orally bioavailable inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor; HGFR) with potential antineoplastic activity. Upon administration, PLB1001 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing or expressing constitutively activated c-Met protein. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.
An orally available inhibitor of human homolog of double minute 2 (HDM2; mouse double minute 2 homolog; MDM2), with potential antineoplastic activity. Upon oral administration, the p53-HDM2 protein-protein interaction inhibitor APG-115 binds to HDM2, preventing the binding of the HDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this HDM2-p53 interaction, the proteasome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This may result in the restoration of p53 signaling and lead to the p53-mediated induction of tumor cell apoptosis. HDM2, a zinc finger protein and a negative regulator of the p53 pathway, is often overexpressed in cancer cells. It has been implicated in cancer cell proliferation and survival.
A cytogenetic abnormality that refers to the translocation of chromosome 10p12 with chromosome 11q23. It is associated with acute myeloid leukemia in childhood.
A cytogenetic abnormality that refers to the translocation of chromosome 11p15 with chromosome 15q35. It results in the formation of NUP98/JARID1A fusion gene. It is associated with the development of acute myeloid leukemia with t(11;15)(p15;q35); NUP98-JARID1A.
A cytogenetic abnormality that refers to the translocation of chromosome 11p15 with chromosome 5q35. It results in the formation of NUP98/NSD1 fusion gene. It is associated with the development of acute myeloid leukemia with t(5;11)(q35;p15); NUP98-NSD1.
A cytogenetic abnormality that involves a translocation between chromosomes 8 and 22.
A cytogenetic abnormality that refers to the translocation of 8p22 and 9p24.1. This translocation results in the fusion of the PCM1 gene and the JAK2 gene.
The dimesylate salt form of LY2228820, a tri-substituted imidazole derivative and orally available, p38 mitogen-activated protein kinase (MAPK) inhibitor with potential anti-inflammatory and antineoplastic activities. Upon administration, ralimetinib inhibits the activity of p38, particularly the alpha and beta isoforms, thereby inhibiting MAPKAPK2 phosphorylation and preventing p38 MAPK-mediated signaling. This may inhibit the production of a variety of cytokines involved in inflammation, cellular proliferation and angiogenesis such as tumor necrosis factor alpha (TNFa), interleukin (IL)-1, -6 and -8, vascular endothelial growth factor, and macrophage inflammatory protein-1 alpha. Ultimately this induces apoptosis and reduces tumor cell proliferation. In addition, inhibition of the p38 MAPK pathway by LY2228820 increases the antineoplastic activity of certain chemotherapeutic agents. p38 MAPK, a serine/threonine protein kinase that is often upregulated in cancer cells, plays a crucial role in tumor cell proliferation, angiogenesis and metastasis.
A chromosomal abnormality where one copy of the short arm of chromosome 9 has been deleted.
An autosomal dominant form of diabetes insipidus caused by mutation(s) in the AVP gene encoding arginine vasopressin.
A molecular genetic abnormality indicating the presence of multiple copies of the AKT3 gene.
A change in the nucleotide sequence of the NBN gene.
A change in the amino acid sequence of Bloom syndrome protein where a frameshift mutation results in the replacement of a tyrosine residue at position 736 with 4 non-canonic amino acids followed by a stop codon.
A change in the nucleotide sequence of the POLD1 gene.
A change in the nucleotide sequence of the CHEK1 gene.
A solitary fibrous tumor/hemangiopericytoma that arises from the central nervous system. It most often corresponds to the tumor previously diagnosed as anaplastic hemangiopericytoma.
A morphologic finding indicating the presence of blasts in a sample of cerebrospinal fluid.
A change in the amino acid residue at position 132 in the isocitrate dehydrogenase [NADP] cytoplasmic protein where arginine has been replaced by glycine.
A response indicating that an individual did not hear ringing or other noises.
An orally bioavailable antagonist of the prostaglandin E2 (PGE2) receptor type 4 (EP4; EP-4), with potential immunomodulating and antineoplastic activities. Upon oral administration, E7046 selectively targets, binds to and blocks the activity of immunosuppressive tumor-associated myeloid cells (TAMCs) in the microenvironment. This abolishes TAMC-dependent immunosuppression and reduces tumor cell proliferation. The presence of immunosuppressive myeloid cells in certain tumors is associated with a poor prognosis.
A topical lotion formulation of the dehydrated, hydrochloride salt form of naloxone, an opiate antagonist, with potential anti-pruritic activity. Upon topical application of the naloxone lotion, naloxone binds to and blocks epidermal mu-opiate receptors. This may suppress or diminish pruritus.
A response indicating that something is or was extremely difficult or impossible.
A change in the nucleotide sequence of the FANCC gene.
A clinical finding about one or more characteristics of HPV-mediated (p16-positive) oropharyngeal cancer, following the rules of the TNM AJCC v8 classification system.
Hypopharyngeal cancer with very advanced local disease. Tumor invades prevertebral fascia, encases carotid artery, or involves mediastinal structures. (from AJCC 8th Ed.)
Goiter associated with reduced thyroid hormone secretion.
Central hypothyroidism due to medical or surgical treatment.
Conditions affecting individuals whose karyotype is 46,XY that is characterized by atypical development of the internal or external sex structures, or the gonads, and in whom no genetic, environmental, or biochemical causation can be established.
A molecular genetic abnormality indicating the presence of multiple copies of the TP53 gene.
A human monoclonal antibody targeting the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), with potential immune checkpoint inhibitory activity. Upon administration, anti-TIGIT monoclonal antibody MTIG7192A binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating T-lymphocytes (TILs), thereby preventing the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like 5; NECL-5). This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as natural killer (NK) cells and CD8+ T-cells, and leads to CD226 dimerization and CD226-mediated signaling. This activates the immune system to exert a T-cell-mediated immune response against cancer cells. TIGIT, a member of the Ig super family and immune inhibitory receptor, plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion, and the inhibition of antiviral immune responses.
Major salivary gland cancer with metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
The identification of a tumor or lesion that is present at baseline, located outside of or independent of any lymph nodes, and is not the target of the therapeutic intervention.
A term that refers to the staging of nasopharyngeal carcinoma according to the American Joint Committee on Cancer, 8th edition.
Nutritional rickets due to dietary deficiency of vitamin D.
Insulin resistance associated with obesity, which may be attributed in part to impaired insulin signaling in target tissues, or impaired insulin-stimulated glucose transport due to reduced expression of the glucose transporter protein 4.
Oropharyngeal (p16-negative) cancer with metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes any with ENE(+). (from AJCC 8th Ed.)
A response indicating that a parent refused the current questionnaire.
A response indicating that an individual prefers or preferred not to answer.
Growth hormone insensitivity syndrome caused by mutation(s) in the STAT5B gene, encoding signal transducer and activator of transcription 5B, a protein critical for the transcription of growth hormone-dependent genes.
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T0, N2, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB (T4b, Any N, M0); (Any T, N3, M0); IVC (Any T, Any N, M1). T4a: Moderately advanced disease. Tumor invades skin, mandible, ear canal, and/or facial nerve. T0: No evidence of primary tumor. T1: Tumor measuring 2 cm or less in greatest dimension without extraparenchymal extension. T2: Tumor measuring more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. T3: Tumor measuring more than 4 cm in greatest dimension, and/or tumor having extraparenchymal extension. T4b: Very advanced disease. Tumor invades skull base and/or pterygoid plates and/or encases carotid artery. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(+); or more than 3 cm but not more than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-), or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). N3: Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or multiple ipsilateral, contralateral, or bilateral nodes any with ENE(+). M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
A response indicating that when an individual has or had bloating, it was very mild.
A response indicating a very low level of confidence or an absence.
A molecular subtype of medulloblastoma associated with activation of the WNT pathway. TP53 mutations may be present or absent. WNT pathway activation in medulloblastomas is associated with good outcome.
An engineered bi-specific monoclonal antibody that targets two different epitopes of the human tumor-associated antigen (TAA) epidermal growth factor receptor 2 (HER2) with potential immunomodulating and antineoplastic activities. After binding to HER2 on the tumor cell surface, anti-HER2 bispecific monoclonal antibody ZW25 induces a cytotoxic T-lymphocyte (CTL) response and antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells that overexpress HER2. Antibody-dependent cellular phagocytosis. (ADCP) is also induced and further stimulates the immune system to kill HER2-overexpressing tumor cells. In addition, binding of ZW25 to HER2 induces receptor internalization, which inhibits HER2 activation, HER2-mediated signaling and HER2-mediated tumor cell growth. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types.
A response indicating that an individual is urinary incontinent or catheterized and unable to manage.
A response indicating that an individual needs help with dressing but can do about half unaided.
A response indicating that an individual has a fecal accident about once per week.
A subjective score of 100% on a scale that ranges from 0%: None to 100%: All of my food.
A cytogenetic abnormality that refers to the translocation of chromosome 11p15 with chromosome 12p13. It results in NUP98-KDM5A fusion and is associated with acute megakaryoblastic leukemia in childhood.
A clinical finding about one or more characteristics of head and neck cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Head and neck cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
A subjective score of 5 on a difficulty falling asleep scale that ranges from 0: No difficulty to 10: Didn't fall asleep.
A subjective score of 8 on a visual analogue scale that ranges from 0: No distress to 10: Extreme distress.
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible. Mucosal extension to lingual surface of epiglottis from primary tumors of the base of the tongue and vallecula does not constitute invasion of the larynx. T1: Tumor 2 cm or smaller in greatest dimension. T2: Tumor larger than 2 cm but not larger than 4 cm in greatest dimension. T3: Tumor larger than 4 cm in greatest dimension or extension to lingual surface of epiglottis. N0: No regional lymph node metastasis. N1: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(-). N2: Tumor with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: (Any T, N3, M0); (T4b, Any N, M0). T4b: Very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery. N3: Tumor with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes any with ENE(+). M0: No distant metastasis. (AJCC 8th ed.)
An acquired coagulation disorder characterized by the partial or complete absence of factor VII activity in the blood.
Unknown primary tumor with metastasis in a single ipsilateral or contralateral cervical lymph node 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral cervical lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
A response indicating that an individual is independently mobile but may require the use of an aid, such as a cane or stick.
An ependymal tumor affecting the cerebellum, fourth ventricle, and brain stem.
Stage IVC includes: T0, Any N, M1. T0: No evidence of primary tumor. M1: Distant metastasis. (AJCC 8th Ed.)
Abnormal outpouching or sac-like dilatation in an artery that originates from he abdominal aorta. [HPO:probinson]
Loss of bone mass occurring beneath the periosteum (the periosteum is the connective-tissue membrane that surrounds all bones except at the articular surfaces). This process may create a serrated and lace-like appearance in periosteal cortical bone. [PMID:24849102]
An abnormally reduced amount of adipose tissue in the thoracic cavity. []
Electron dense deposits at the glomerular basement membrane,
The presence of a localized dilatation or ballooning of a cerebral artery. [HPO:probinson]
A type of third degree heart block in which the escape rhythm arises at a relatively low part of the conduction system (below the atrioventricular node), which produces a wide QRS complex. []
A localized outpouching of ventricular cavity that is generally associated with dyskinesia and paradoxical expansion during systole. [HPO:probinson]
Presence of multiple dilatations (sac-like outpouchings) in the blood vessels of the conjunctiva. [HPO:probinson]
Abnormal outpouching or sac-like dilatation of one of the anatomic dilations of the ascending aorta, which occurs just above the aortic valve. [UBERON_0003707]
Abnormal outpouching or sac-like dilatation in the wall of the inferior mesenteric artery or superior mesenteric artery . [HPO:probinson]
A bulging of the interatrial septum towards one side. In adults, atrial septal aneurysm can be defined as a protrusion of the aneurysm of >10 mm beyond the plane of the atrial septum as measured by transesophageal echocardiography. [HPO:probinson, pmid:7758185]
A dilatation (balooning or bulging out of the vessel wall) of a carotid artery. [HPO:probinson]
The presence of complement 3 deposits in the glomerulus. [Eurenomics:ewuehl]
Focal proliferation of glial cells in the hypothalamus.
Swelling within the basal ganglia due to the accumulation of fluid.
Swelling within the thalamus due to the accumulation of fluid.
A morphological anomaly of lymph nodes in the mesenteric root or throughout the mesentery.
Increase in size of one or more mesenteric lymph nodes.
A deviation from normal of the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS).
A decrease in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS).
A deviation from normal in the level of choline-containing compounds in the brain identified by magnetic resonance spectroscopy (MRS).
An decrease in the level of choline-containing compounds in the brain identified by magnetic resonance spectroscopy (MRS).
An increase in the level of creatine in the brain identified by magnetic resonance spectroscopy (MRS).
A decrease in the level of creatine in the brain identified by magnetic resonance spectroscopy (MRS).
A deviation from normal in the level of N-acetyl aspartate in the brain identified by magnetic resonance spectroscopy (MRS).
An increase in the level of N-acetyl aspartate in the brain identified by magnetic resonance spectroscopy (MRS).
A structural anomaly of the olfactory lobe, the structure within the brain that receives neural input from the nasal cavity and thereby processes the sense of smell.
Single (solitary) abscess in the spleen.
Strabismus in which the angle of deviation differs depending upon the direction of gaze or according to which eye is fixing, associated with: (i) defective movement of the eye, (ii) asymmetrical accommodative effort.
Direction of the U wave opposite to the T wave (i.e., below baseline) in leads with upright T waves.
U wave inversion that is induced by exercise stress testing.
An anomaly of the complex formed by the Q, R, and S waves, which occur in rapid succession on the electrocardiogram.
Abnormal amplitude of the QRS complex of the electrocardiogram (EKG).
Any structural anomaly of the elastic fibers of the skin. Elastic fibers are the essential extracellular matrix macromolecules comprising an elastin core surrounded by a mantle of fibrillin-rich microfibrils.
Passage of many stools containing blood and mucus.
Area of skin requiring an increased amount of time to return to its original shape after being stretched.
A structural anomaly of the mucous lining of the large intestine.
A retinal exudate in the area surrounding the optic nerve head.
A subretinal scar with a disc-like shape in the region of the macula.
Structural abnormality of the hypothalamus related to defective development.
Structural abnormality of the thalamus related to defective development.
Any structural anomaly of the hippocampus,
Structural abnormality of the hippocampus related to defective development.
Structural abnormality of the basal ganglia related to defective development.
A variant of port-wine stain characterized by a pale red or even pink tone, in contrast to the darker hue of the port-wine stain. By analogy with the term port-wine stain, this variant rose-wine stain, or nevus roseus. Nevus roseus, however, cannot be definitely diagnosed until adulthood as port-wine stains are sometimes pink in children. While the natural history of port-wine stains includes hypertrophy, darkening, and nodularity, nevus roseus remains unchanged for life.
Decrease in the activity of pyruvate kinase (PK) within erythrocytes. PK catalyzes the reaction: ATP + pyruvate = ADP + phosphoenolpyruvate.
Yellow/white, sharply delineated lesion, typically of inflammatory nature, involving the macula.
Ret pegs (or ridges) are the epithelial extensions that project into the underlying connective tissue in both skin and mucous membranes. Rete ridge flattening refers to the loss of these projections so that the skin epithelium acquires a relatively flat appearance.
An alteration of the color of the lip to take on a violet color. This term does not include cyanosis.
A type of epidermal acanthosis characterized by a jagged (sawtooth) appearance of the rete ridges of the epidermis.
Areas of white discoloration visible on the surface of the teeth (enamel) in the form of streaks or specks.
White lesions of the oral mucosa are generally caused by a condition that increases the thickness of the epithelium. This increases the distance to the vascular bed and thereby tends to change the usual reddish color of the oral mucosa to white. Common causes include hyperkeratosis (thickening of the keratin layer), acanthosis (thickening of the spinous cell layer), increased edema in the epithelium (leukoedema), and reduced vascularity of the underlying lamina propria. Additionally, fibrin caps od surface ulcerations and collapsed bullae can appear white.
An abnormally reduced amount of adipose tissue in the abdominal cavity.
A structural anomaly of the mucous lining of the small intestine.
Lactase is produced in the small intestine in humans, Lactase is a member of the beta-galactosidase family of enzymes, and hydrolyzes D-lactose to form D-galactose and D-glucose, which can be absorbed by the small intestine. There are many ways of assessing lactase activity. In one test, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a color reaction develops within 20 min as a result of hydrolyzed lactose (a positive result) in patients with normolactasia, whereas no reaction (a negative result) develops in patients with severe hypolactasia. Other, less direct, tests include the hydrogen breath test, and blood tests following lactose challenges. []
A deviation from normal concentration of the hormone estrogen in the blood circulation.
A deviation from normal concentration of estriol in the circulation.
An elevation above normal limits of estriol concntration in the circulation.
A reduction below normal limits of estriol in the circulation.
A deviation from the normal concentration of circulating estrone.
An elevation above normal limits of the concentration of estrone in the circulation.
A reduction below normal limits of the concentration of estrone in the circulation.
Ectopic deposition of calcium salts found in the gingiva.
Deterioration of the tissue of the fovea, i.e.,the region of sharpest vision within the macula of theretina.
A shiny appearance of the macula, which is often called a beaten bronze appearance.
A fluorescein angiographic finding of absence of the normal background fluorescence (a dark choroid).
Partial or complete wasting (loss) of muscularois propria tissue that was once present. The atrophy may involve a marked vacuolar degeneration of myocytes, loss of muscle fibers and some cases a highly characteristic honeycomb fibrosis.
Lack of visual responsiveness or decrease in visual capabilities suggesting a lack of visual responsiveness or decrease in visual capabilities in an infant or young child in which visual behvior fails to meet normal developmental milestones.
Presence of biliary veins that serve as a collateral channel to the systemic circulation
A fiunctional anomaly of the hepatobiliary system
Inability to be weaned from intravenous (parenteral) nutrition, as judged by the hydration status (urine output, blood urea nitrogen, creatinine, urine sodium concentration), ability to maintain weight, stool output, and serum electrolyte status.
Increased amount of autofluorescence in the retina as ascertained by fundus autofluorescence imaging.
Decreased amount of autofluorescence in the retina as ascertained by fundus autofluorescence imaging.
A temper tantrum is an emotional outburst usually triggered by a sense of frustration and manifested as whining and crying, screaming, kicking, hitting, and breath holding. Temper tantrums are normal in toddlers and young children and usually happen between the ages of one to three years. Temper tantrums may be considered abnormal if they occur at an unusually high frequency, are of unusual severity, or occur at an old age than usual.
Temper tantrums that occur more frequently than usual.
Temper tantrums whose severity is more severe than usual. For instance, a temper tantrum might be considered to be severe if a child loses control so completely that the child cannot control the tantrum on its own, continuing until it becomes exhausted or a parent intervenes.
A structural abnormality of the optic chiasm.The optic chiasm, located below the hypothalamus, is a partial crossing of the optic nerves.
An elevated number of elastic fibers, that is of bundles of proteins and glycoproteins in the extracellular matrix in the reticular dermis. Elastic fibers can stretch and recoil back to their original length. This feature can be appreciated on histology with hematoxylin and eosin or other staining methods.
Formation of clumps or aggregates that make up small protuberances from elastic fibers within the dermis (especially the reticular dermis).
An increase of the diameter of elastic fibers in the dermis.
Elastic fibers in the dermis exhibit an increased number of breaks associated with disorganization of the structure of the elastic fibers.
Thickening of the interlobular septa of the lungs as seen on a high-resolution computed tomography scan with a smooth appearance of the interlobular septa.
Thickening of the interlobular septa of the lungs as seen on a high-resolution computed tomography scan with a nodular or beaded appearance of the interlobular septa.
Thickening of the interlobular septa of the lungs as seen on a high-resolution computed tomography scan with an irregular appearance of the interlobular septa. THis feature is often associated with distortion of lung architecture.
A fine reticular pattern on high-resolution computeed tomography, with the visible lines separated by a few millimeters. Regions of the lung with intralobular interstitial thickening characteristically show a fine lacelike or netlike appearance.
Thickening of the peribronchovascular interstitium, a connective tissue sheath that surrounds the central bronchi and pulmonary arteries. The peribronchovascular interstitium extends from the level of the pulmonary hila into the peripheral lung. This feature may be ascertained on high-resolution computer tomography.
Increase in thickness of the subpleural interstitium.
A descriptive term that is applied to computer tomography imaging and that refers to a hazy area of increased attenuation in the lung with preserved bronchial and vascular markings.
A hazy area of increased attenuation in centrilobular areas of the lung with preserved bronchial and vascular markings seen on a computer tomography scan. Centrilobular refers to a location that is central within secondary pulmonary lobules.
An abscess-like lesion located within the abdomen. The lesions are localized in the spleen, liver, abdominal lymph nodes. The lesions represent visceral sterile collections of mature neutrophils that do not respond to antibiotics but regress quickly when treated with corticosteroids, but relapses occur frequently.
A confined region of lax skin that hangs below the level of the surrounding skin. Histopatholigically, there is a loss of elastic fibers in the dermis of the affected region.
A type of generalized tonic-clonic seizure that occurs in and rapidly engages bilaterally distributed networks.
Areas of brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter that surrounds the fourth cerebral ventricle (which is located beneath the tentorium of the cerebellum).
A congenital diaphragm defect involving the central tendinous (e.g., amuscular) portion of the diaphragm, whereby the entire rim of diaphragmatic musculature is present.
A non-malignant sessile or pedunculated polyp in the colon and rectum that displays a cap of inflammatory granulation tissue with fibrinopurulent exudate that covers the polyp.
A deviation from the normal concentration in blood of an apolipoprotin, i.e., of a protein that binds lipids to form lipoprotein and is thereby responsible for the transport of lipids in the blood and lymph circulation.
An increased concentration in blood of apolipoprotein A-IV, a major component of HDL and chylomicrons that has a role in VLDL secretion and catabolism and is required for efficient activation of lipoprotein lipase by ApoC-II.
Applies to a sign or symptom that is provoked or brought about by breast feeding in an infant.
Applies to a sign or symptom that is provoked or brought about by exposure to cold surroundings.
Applies to a sign or symptom that is provoked or brought about by being dehydrated, i.e., by a deficit in total body water.
Applies to a sign or symptom that is provoked or brought about by eating or drinking carbohydrates.
Applies to a sign or symptom that is provoked or brought about by eating or drinking fructose.
Applies to a sign or symptom that is provoked or brought about by eating or drinking glucose.
Applies to a sign or symptom that is provoked or brought about by drinking or otherwise ingesting ethanol.
Applies to a sign or symptom that is provoked or brought about by abstaining from eating food (fasting).
Applies to a sign or symptom that is provoked or brought about by eating or drinking galactose. Galactose usually is ingested as lactose, which is composed of equimolar amounts of glucose and galactose.
Applies to a sign or symptom that is provoked or brought about by exposure to heat.
Applies to a sign or symptom that is provoked or brought about by febrile illness.
Applies to a sign or symptom that is provoked or brought about by eating large quantities of food, for instance, by a heavy meal.
Applies to a sign or symptom that is provoked or brought about by eating a diet high in lipids.
Applies to a sign or symptom that is provoked or brought about by excessively rapid and deep breathing.
Applies to a sign or symptom that is provoked or brought about by a vaccination.
Applies to a sign or symptom that is provoked or brought about by menstruation in a female.
Applies to a sign or symptom that is provoked or brought about by pregnancy in a female.
Applies to a sign or symptom that is provoked or brought about by a lack of sufficient sleep.
Applies to a sign or symptom that is provoked or brought about by smoking.
Applies to a sign or symptom that is provoked or brought about by eating or drinking sodium.
Applies to a sign or symptom that is provoked or brought about by exposure to sound or noise.
Applies to a sign or symptom that is provoked or brought about by a physical, mental, or emotional factor associated with bodily or mental tension.
Applies to a sign or symptom that is provoked or brought about by a a state of excitement or by being startled.
Applies to a sign or symptom that is provoked or brought about by a sudden movement.
Applies to a sign or symptom that is provoked or brought about by vestibular stimulation, including head turning, cold calorics, postural changes, or rotating chair.
A structural anomaly of a synovial bursa.
A parasomnia that occurs in non-rapid eye movement (NREM) sleep. This refers to a disorder of arousal that occurs during during slow-wave sleep (ie, NREM stage 3 sleep).
Applies to a sign or symptom that is improved or made more bearable by pregnancyin a female.
Applies to a sign or symptom that is improved or made more bearable by heat (including fever).
Applies to a sign or symptom that is improved or made more bearable by eating or drinking carbohydrates including glucose (sugar).
Any physiological abnormality of the esophagus.
Any functional anomaly of the skin adnexa (skin appendages), which are specialized skin structures located within the dermis and focally within the subcutaneous fatty tissue, comprising three histologically distinct structures: (1) the pilosebaceous unit (hair follicle and sebaceous glands); (2) the eccrine sweat glands; and (3) the apocrine glands.
Sweating provoked by cold temperature rather than by heat.
Applied to a sign or symptom that is aggravated by activity, exertion, or exercise.
An abnormal pupil shape that is elliptical, i.e., egg-like.
Applies to a sign or symptom that is worsened, aggravated, or exacerbated by head trauma.
Leakage of fluorescein dye observed upon retinal fluorescein angiography. Areas of leakage can be appreciated as showing gradual enlargement with blurring of margins.
Reduced dimension of the solid part of the kidney (parenchyma, the renal cortex and medulla) as measured from the collecting system (renal calyces and pelvis) to the border of the kidney. This measurement can be performed by measuring the thickness of the parenchyma in computed tomography scans.
A limitation of the ability to direct one's gaze below the horizontal meridian.
A limitation of the ability to direct one's gaze above the horizontal meridian.
An anomaly of the outer shell (cortex) of a foot bone.
A reduction in the thickness of the outer shell (cortex) of foot bones.
Applies to a sign or symptom that is provoked or brought about by a strong spontaneously arising mental state, reaction or feeling (emotion).
A failure to achieve the ability to stand up at an appropriate developmental stage. Most children begin to walk alone at 11 to 15 months of age. On average, children can stand while holding on at the age of 9 to 10 months, can pull up to stand and walk with one hand being held at 12 months, and can stand alone and walk well at 18 months.
A failure to achieve the ability to sit at an appropriate developmental stage. Most children sit with support at 6 months of age and sit steadily without support at 9 months of age.
A ring of redness at the limbus of the eye, the border between the cornea and the sclera.
Prominence of blood vessels of the superficial episcleral tissues.
Prominence of blood vessels of the deep episcleral tissues.
Damage to and and obliteration of intrahepatic bile ducts (bile ducts that transport bile between the Canals of Hering and the interlobar bile ducts).
A deviation from the normal concentration of beta-2-microglobulin in the blood.
Elevated concentration of beta-2-microglobulin in the blood.
Reduced concentration of beta-2-microglobulin in the blood.
An anomaly of the margin of the cornea overlapped by the sclera.
Swelling of the margin of the cornea overlapped by the sclera.
Conjunctival papillae with a diameter Giant papillae greater than 1 millimeter.
A history of repeated fungal infections located between the fingers or toes, usually manifested by scaling, maceration, and itching. The toes are more commonly affected than the fingers.
An anomaly of cellular morphology or physiology.
A type of myoclonus in which the myoclonias shift from body region to another in a random and asynchronous fashion. Erratic myoclonus can affect the face or limbs, are brief, single or repetitive, very frequent and nearly continuous.
An abnormal polygonal shape of the calices of the kidney (which normally have a rounded or cup-shaped appearance).
Increased number of calices of the kidney.
A structural anomaly of the pyramid of the adult kidney, cone-shaped structures with a broad base adjacent to the renal cortex and the narrow apex that is termed papilla.
Undergrowth of the pyramid of the adult kidney, cone-shaped structures with a broad base adjacent to the renal cortex and the narrow apex that is termed papilla.
Hypercellularity due to increased number of cells within glomerular capillary lumina, causing narrowing of the lumina.
Hypercellularity (increased number of cells) in the renal glomerulus but external to the glomerular capillaries, i.e., in the Bowman space or more than one layer of parietal or visceral epithelial cells.
A structural anomaly of the growth plates (epiphyseal plates), areas of cartilage located near the ends of long bones that are located between the metaphysis (widened part of the shaft of the bone) and the epiphysis (end of the bone) and in which growth occurs in the developing bone. After conclusion of bone growth, the growth plates ossify (harden into solid bone).
Increased thickness (dimension along the axis of the bone) of the growth plate.
Abnormal bone tissue formation (ossification) affecting the sacrum.
Formation of the sacrum bone tissue occurs later than age-adjusted norms.
Interictal refers to a period of time between epileptic seizures. Electroencephalographic (EEG) patterns are important in the differential diagnosis of epilepsy, and the EEG is almost always abnormal during a seizure. Some persons with seizures may show EEG abnormalities between seizures, while others do not. In some cases, multiple interictal EEGs must be recorded before an abnormality is observed. In most cases the electrographic pattern of seizure onset is completely different from the activity recorded during interictal discharge.
The presence of two distinct odontoid processes. The odontoid process, also known as the dens of the axis, is a protuberance of the C2 vetebral body around which the first vertebra rotates.
Os odontoideum is classified into two anatomic types (orthotopic and dystopic). Os odontoideum is defined as an ossicle that consists of smooth and separate caudal portions of the odontoid process.With dystopic os odontoideum, the ossicle is located near the basion or is fused with the clivus.
An increased concentration of glutamine in the urine.
Applies to a sign or symptom that is provoked or brought about by exertion or physical exercise.
Areas of subcutanous fat tissue that are resistant to (do not respond as expected to) diet, life-style alteration, or bariatric surgery.
Areas of subcutanous fat tissue below the waist that are resistant to (do not respond as expected to) diet, life-style alteration, or bariatric surgery.
High-resolution computed tomography (HRCT) can distinguish findings that characterize characterise interstitial lung diseases in a way not possible with other modalities.
On pulmonary high-resolution computed tomography, reticular pattern is characterised by innumerable interlacing shadows suggesting a mesh.
The so-called crazy paving pattern is characterised on HRCT by the presence of thickened interlobular septae and intralobular lines superimposed on a background of ground-glass opacity, resembling irregularly shaped paving stones.
A nodular pattern is characterised on pulmonary high-resolution computed tomography by the presence of numerous rounded opacities that range from 2 mm to 1 cm in diameter, with micronodules defined as smaller than 3 mm in diameter.
Co-occurrence of reticular and micronodular patterns on pulmonary high-resolution computed tomography.
On pulmonary high-resolution computed tomography, the cystic pattern is composed by well-defined, round and circumscribed air-containing parenchymal spaces with a well-defined wall and interface with normal lung. The wall of the cysts may be uniform or varied in thickness, but usually is thin (less than 2 mm) and occurs without associated emphysema.
Co-occurrence of the cystic pattern and the ground-glass pattern on pulmonary high-resolution computed tomography,
Areas of low density corresponding to parenchymal destruction and reduced perfusion, and attenuation of the pulmonary vasculature, as visualized on pulmonary high-resolution computed tomography.
A patchwork of intermingled areas of increased and decreased attenuation visualized on pulmonary high-resolution computed tomography.
A nodular pattern on pulmonary high-resolution computed tomography that has a perilymphatic distribution.
A nodular pattern on pulmonary high-resolution computed tomography that displays a tree-in-bud pattern, representing centrilobular branching structures that resemble a budding tree.
A nodular pattern on pulmonary high-resolution computed tomography that has an apparently random pattern.
A habitual positioning of the body with the head and upper back bent forward.
A deficit in the ability to fixate eye movements in order to stabilize images on the retina
Any anomaly of the structure of the spleen.
Any anomaly of the function of the spleen.
A type of urethral stricture affecting the fossa navicularis, which is the spongy part of the male urethra located at the glans penis.
A type of urethral stricture affecting the pendulous urethra, which is straight and fixed to the corpora cavernosa.
A type of urethral stricture affecting the bulbar urethra, which is the part of the urethra that traverses the root of the penis.
Urethra more open or expanded than normal.
A type of of pulmonary hemorrhage that originates from the pulmonary microcirculation, including the alveolar capillaries, arterioles, and venules. It presents with hemoptysis, anemia, diffuse lung infiltration, and acute respiratory failure. The diagnosis is confirmed by the observation of the accumulation of red blood cells, fibrin, or hemosiderin-laden macrophage in the alveolar space on pathologic biopsy. Hemosiderin, a product of hemoglobin degradation, appears at least 48-72 hours after bleeding and is helpful in distinguishing diffuse alveolar hemorrhage from surgical trauma. Mild interstitial thickening, organizing pneumonia, or diffuse alveolar damage can also be seen.
Any anomaly of the structure of the larynx.
Any anomaly of the function of the larynx.
Any anomaly of the function of the bronchi. []
Any anomaly of the function of the bronchi.
A type of cry that is abnormal because it is consists of unusually shortened and detached vocalizations.
Reduced activity of the enzyme lecithin cholesterol acyl transferase.
A diminished activity of the classical complement pathway as measured by the assay for 50% haemolytic complement (CH50) activity of serum.
Increased concentration of 11-deoxycortisol in the circulation. 11-deoxycorticosterone, which is also known as simply deoxycorticosterone and 21-hydroxyprogesterone, is a steroid hormore that is produces in the adrenals and is a precursor to aldosterone.
Ectopic deposition of calcium salts in the Achilles tendon.
An abnormality of the function of the cardiac atria.
A decrease in the volume (size) of the amygdyla.
Any structural anomaly of the papillary muscles of the left ventricle.
A congenital malformation in which one or both of the papillary muscles (posteromedial or anterolateral) insert directly (that is, without interpositioned chordae tendineae) into the anterior mitral leaflet.
Abnormal location of the insertion of a papillary muscle into the left ventricular wall.
Abnormally anterior location of the papillary muscles of the left ventricle.
Abnormal location of the insertion of the anterolateral papillary muscle near to the apex of the left ventricle. This feature may be appreciated by noting that this muscle is usually not seen in the apical level of the parasternal short-axis echocardiographic view,
Testicular adrenal rest tumor (TART) isa abenign tumor of the testis. TART generally occurs multiply and bilaterally within the rete testis. Histologically, TART resemble adrenocortical tissue, which led to the name. The tumous are not encapsulated and consist of sheets or confluent cords of large polygonal cells with abundant eosinophilic cytoplasm.
Any deviation from the normal range of concentration of a metabolite in the cerebrospinal fluid.
CSF 5-HIAA (5-hydroxyindolacetic acid) level is below the lower limit of normal.
Any deviation from the normal range of a protein concentration in the cerebrospinal fluid.
CSF total protein level is below the lower limit of normal.
An increase above normal limits of the ratio of the cerebrospinal fluid (CSF) albumin concentration to serum albumin concentration.
An elveated level of myoinositol in the brain identified by magnetic resonance spectroscopy (MRS).
An abnormality of the processes that maintain the redox environment of a cell or compartment within a cell, that is, the balance between reduction and oxidation chemical reactions.
An accumulation of free radical groups in the body inadequately neutralized by antioxidants, which creates a potentially unstable and damaging cellular environment linked to tissue damage.
A deviation from the normal conentration of beta globulin. The beta globulins are a group of globular (globe-shaped) proteins in blood.
Increased level of beta 2-microglobulins in the urine.
A hamartomatous proliferation containing malformed hair follicles in various stages of development. Panfolliculomas are well-circumscribed lesions demonstrating all stages of follicular differentiation.
A history of repeated fungal infections located on the sole of the foot, usually manifested by scaling, maceration, and itching.
A plaque (a solid, raised, plateau-like (flat-topped) lesion greater than 1 cm in diameter) with a red or reddish color often associated with inflammation or irritation.
An abnormal result of the perchlorate discharge test. In this test, first radioactive iodine is administered, sufficinet time is allowed to pass so that the radioactive iodine is captured by the thyroid,and then, perchlorate is administered orally. The perchlorate displaces non-organified iodide from the thyroid. The perchlorate dischanrge test is considered positive (abnormal) if there is an abnormally rapid loss of radioactive iodine from the thyroid.
A deviation from the normal concentration of thyroglobulin, a protein produced in the thyroid gland that acts as a precursor to thyrroid hormones.
An abnormal elevant of the concentration of thyroglobulin, a protein produced in the thyroid gland that acts as a precursor to thyrroid hormones.
A small pupil (typically diameter less than 2 mm) that dilates poorly or not at all in response to topically administered mydriatic drugs.
Redness of the skin of the palm of the hand and the sole of the foot caused by hyperemia of the capillaries in the lower layers of the skin.
Regular circumferential periaortic fibrosis involving the whole aorta and leading to a coated aorta appearance on computed tomography scans
Significant luminal narrowing of a long segment of the descending aorta.
Any anomaly of the function of a coronary artery.
Obesity with a body mass index of 30 to 34.9 kg per square meter.
Origin of the right coronary artery (RCA) from the left sinus of Valsalva orof the left main (LM) or left anterior descending (LAD) coronary artery from the right sinus of Valsalva.
The circumflex coronary artery originates from the right aortic sinus of Valsalva.
Origin of the right coronary artery (RCA) from the left sinus of Valsalva orof the left main (LM) or left anterior descending (LAD) coronary artery from the right sinus of Valsalva, with the additional feature that the artery passes between the two great arteries. This carries a risk of the artery being compressed by these two vessels,
A solitary yellow-orange slightly raised plaque typically on scalp or face. The plaque typically thickens and becomes more verrucous or pebbly during childhood.
A papule with the same color as the surrounding skin.
Later than normal development of the breasts.
A congenital malformation with abnormal connection between one of the coronary arteries and the pulmonary artery.
An abnormality of gaze that can be observed following an acute supranuclear cerebral lesion (e.g., stroke) that is characterized by an acute inability to direct gaze contralateral to the side of the lesion and is accompanied by a tendency for tonic deviation of the eyes toward the side of the lesion.
The percentage of fat as a part of total body weight above the norm, usually defined as 32% for females and 25% for males.
Abnormal increased in length of the chordae tendinae of the mitral valve.
A structural anomaly of the chordae tendinae of the mitral valve, whose main function is to transmit the contraction and relaxation of the papillary muscles during the cardiac cycle, thus ensuring the closing of the leaflets of the mitral valve.
Loss of the outer layer of the epidermis in large, scale-like flakes localized to the palm of the hand and the sole of the foot. []
Loss of the outer layer of the epidermis in large, scale-like flakes localized to the palm of the hand and the sole of the foot.
Loss of the outer layer of the epidermis in large, scale-like flakes localized to one or more fingertips.
A skin lesions that resembles the lesions observed in psoriasis, viz., an erythematous plaque covered by fine silvery scales. Psoriasiform lesions can be observed in psoriasis as well as in other conditions including allergic contact dermatitis, seborrhoeic dermatitis, Atopic dermatitis, pityriasis rubra, and lichen simplex chronicus. []
A skin lesions that resembles the lesions observed in psoriasis, viz., an erythematous plaque covered by fine silvery scales. Psoriasiform lesions can be observed in psoriasis as well as in other conditions including allergic contact dermatitis, seborrhoeic dermatitis, Atopic dermatitis, pityriasis rubra, and lichen simplex chronicus.
A skin lesion with a snake- or serpent-like distribution.
A lesion of the skin with a ring-like distribution.
The presence of multiple xanthomas (xanthomata) in the skin distributed in the creases of the palm of the hand. Xanthomas are yellowish, firm, lipid-laden nodules in the skin.
The Harlequin phenomenon consists of a sudden change in skin colour, resulting in two different body colours, one on eachhalf of the body.
With the pathergy test, a small, sterile needle is inserted into the skin of the forearm. The site of injectionis circuled and observed after one and two days. If a small red bump or pustule at the site of needle insertion occurs, the pathergy test is considered to have a positive (abnormal) result.
Erythematous, poikilodermatous macules distributed in a shawl pattern over the shoulders, arms and upper back.
Erythematous, poikilodermatous macules distributed in a V-shaped distribution over the anterior neck and chest.
Any abnormality in the proportion T cells subsets relative to the total number of T cells.
A saccular or fusiform dilation and elongation of the ductus arteriosus. [PMID:11788230, UToronto:chum]
A structural anomaly of the nonstriated, involuntary muscle tissue of the intestine.
Abnormal layering of the intestinal muscularis propria into three layers; (1) inner circular; (2) additional oblique; and (3) outer longitudinal layer.
The presence of excessive fibrous connective tissue in the muscularis propria of the intestine. Fibrosis is a reparative or reactive process.
Aggregates of stainable substances (proteins) in the nuclei of enteric neurons.
An increased thickness of the eyelid not related to acute inflammation.
Increased activity of the enzyme gamma-glutamyltransferase (GGT). GGT is mainly present in kidney, liver, and pancreatic cells, but small amounts are present in other tissues.
An abnormal accumulation of protein in the glomerulus.
Multiple cream-yellow colored hypopigmented choroidal anomalies whose size is approximately one quarter to one half of that of the optic disc, and whose location tends to cluster around the optic nerve radiating towards the periphery. The pattern of the lesions is said to be similar to gunshot spatter from birdshot.
An anomaly of the electrical conduction physiology of the heart.
Bowing (bulging out) of the membranous part of the interventricular septum of more than 10-15 mm into the cavity of an adjacent ventricle (usually into the right ventricle). [PMID:5846101, PMID:6018320]
Bowing (bulging out) of the membranous part of the interventricular septum of more than 10-15 mm into the cavity of an adjacent ventricle (usually into the right ventricle).
Bowing (bulging out) of the muscular part of the interventricular septum of more than 10-15 mm into the cavity of an adjacent ventricle (usually into the right ventricle).
A structural anomaly affecting a blood vessel involved in the circulation of the heart, i.e., the superior or inferior vena cava, the pulmonary arteries, the pulmonary veins, and the aorta.
An abnormality of the structure of the pulmonary artery.
An abnormality of the function of the pulmonary artery.
An abnormality of the structure of the pulmonary veins.
An abnormality of the function of the pulmonary veins.
An abnormality of the function of the veins that return deoxygenated blood from the body into the heart, i.e., the superior vena cava and the inferior vena cava.
An abnormality of the structure of the veins that return deoxygenated blood from the body into the heart, i.e., the superior vena cava and the inferior vena cava. []
A chronic deviation from normal pressure in the systemic arterial system.
An abnormal curved or vaulted (capped) structure covering the middle third of the dorsal pontine tegmentum and projecting into the fourth ventricle.
A deviation from the normal activity of coagulation factor VIII. Factor VIII (fVIII) is a cofactor in the intrinsic clotting cascade that is activated to fVIIIa in the presence of minute quantities of thrombin. fVIIIa acts as a receptor, for factors IXa and X.
Increased activity of the coagulation factor VIII. Factor VIII (fVIII) is a cofactor in the intrinsic clotting cascade that is activated to fVIIIa in the presence of minute quantities of thrombin. fVIIIa acts as a receptor, for factors IXa and X.
A reduction below normal limits of the ratio of the cerebrospinal fluid (CSF) albumin concentration to serum albumin concentration.
Enlargement of the large blood vessels in the choroid.
An decrease in the level of glutamine in the brain identified by magnetic resonance spectroscopy (MRS).
A deviation from the normal range of the ratio of the albumin concentration in the cerebrospinal fluid (CSF) to the concentration in serum (which may be defined as 3.2-9.0). This is an index of blood-brain barrier (BBB) integrity, adjusted for the serum albumin concentration, and an increased ratio is taken as a sign of a loss of integretiy of the BBB with leakage of albumin into the CSF.
A reduction in the concentration of bile acid in the blood.
Hyperplasia of lining epithelia of the septal and large bile ducts manifesting as micropapillary projections or as a stratification of the epithelium with or without dilatation of the duct lumen.
Cholangitis characterized by the accumulation of granulomas. Granulomas are aggregates of modified macrophages (epithelioid cells) and other inflammatory cells that accumulate after chronic exposure to antigens. The underlying trigger may be exposure to noxious agents that cannot be biochemically degraded or to immune dysfunction. The ultimate result is a release of a variety cytokines that stimulate mononuclear cells that fuse to form multinucleated giant cells with a surrounding rim of lymphocytes and fibroblasts.
Cholangitis characterized by a close association between duct branches, usually interlobular bile ducts, and lymphocytic aggregates, which may show a follicular arrangement.
Cholangitis associated with mixed inflammatory infiltrates and the presence of fibrosis or sclerosis of the biliary tree.
Any structural anomaly of the pancreatic duct, which is the tubular structure that collects exocrine pancreatic secretions and and transports them to the duodenum.
A congenital anomaly characterized by the presence of two separate pancreatic ducts.
Any structural anomaly of the saccule of the vestibule. The saccule is the otolith organ that senses motions in the sagittal plane (i.e., up-down movement).
Deterioration or loss of the tissues of the saccule of the vestibule.
A nerve fascicle or fasciculus is a small bundle of axons, enclosed by the perineurium. A minifascule refers to a group of thinly myelinated and unmyelinated axons surrounded by a delicate perineurium, and with a smaller diamter than a normal nerve fascicle.
Areflexia that is limited to one side of the body.
An accessory phalanx of the third (middle) finger that is arranged linearly with the other phalanges. Hyperphalangy results from an accessory ossification center at the metacarpophalangeal joint, resulting in radial deviation of the finger.
Yellow-colored streaks, patches, or spots on the intimal surface of arteries. Fatty streaks stain red with Sudan III or Sudan IV.
Sclerosis of the intrahepatic portal veins of the liver and generally accompanied by non-cirrhotic portal hypertension, features of which may include splenomegaly and varices. [PMID:25796481]
Sclerosis of the intrahepatic portal veins of the liver and generally accompanied by non-cirrhotic portal hypertension, features of which may include splenomegaly and varices.
Areas of radio-opaque sclerotic bands alternating with those of normal lucency give rise to stripes akin to a zebra. [PMID:28384951]
Areas of radio-opaque sclerotic bands alternating with those of normal lucency give rise to stripes akin to a zebra.
Nuclear lobes of neutrophils in the bone marrow are thickend and condensed, and individual lobes are connected by unusually long chromatin filaments. []
An increased blood concentration of the carcinoembryonic antigen (CEA). CEA is a member of the immunoglobulin supergene family. The human CEA gene family is clustered on chromosome 19q and comprises 29 genes. CEA is highly expressed in embryonic tissue and in some cancers, and is a widely used tumor marker.
An increased blood concentration of carcinoma antigen 125 (CA-125). CA-125, also known as mucin 16, can exhibit increased blood levels in certain types of cancer.
A deviation from normal blood concentration of retinol-binding protein (RBP). The most commonly used indicator of vitamin A status is the serum retinol concentration (retinol is one of the several compounds known as vitamin A). The serum RBP concentration is used as a surrogate measure for serum retinol.
A reduced blood concentration of retinol-binding protein. This finding predicts vitamin A deficiency with high sensitivity and specificity.
The kidney contributes towards acid-base homeostasis by excreting H+ ions and retaining bicarbonate. This process is known as acidification of the urine. The pH of urine ranges normally from 4.5 to 8. The inability to reduce the pH of the urine in a situation where it would be otherwise expected is known as an acidification defect.
A deviation from the normal blood concentration of the insulin like growth factor binding protein acid labile subunit (IGFALS; Entrez Gene ID 3483). The acid-labile subunit (IGFALS) acts in the insulin-like growth (IGF) system by binding circulating IGF1 in a ternary complex with binding protein (IGFBP)-3 to prevent IGF1 from crossing the endothelial barrier.
A decreased blood concentration of growth hormone binding protein.
Blood concentration of insulin-like factor 3 (ILF3) is below normal limits.
A type of maturation arrest in which only spermatogonia or spermatocytes are found.
A type of maturation arrest in which spermatids are detected without spermatozoa.
Bullae (defined as fluid-filled blisters more than 5 mm in diameter with thin walls) of the skin with an acral distribution (affecting peripheral regions such as hands and feet=.
A developmental defect characterized by lack of a soft palate.
An abnormal immunoglobulin light chain in the circulation and typically produced by a clonal population of B-cell derived plasma cells.
An abnormal immunoglobulin heavy chain in the circulation and typically produced by a clonal population of B-cell derived plasma cells.
An abnormal immunoglobulin (heavy and light chain) in the circulation and typically produced by a clonal population of B-cell derived plasma cells.
An elevation in bone density in one or more tarsal bones of the foot. Sclerosis is normally detected on a radiograph as an area of increased opacity.
Increased blood concentration of vascular endothelial growth factor (VEGF).
Narrowing or constriction of the aorta localized to the region of the transverse aortic arch.
Coarctation of the aorta is a narrowing or constriction of a long segment of the arch of the aorta.
A deviance from the norm of the origin or course of the right brachiocephalic artery, the left common carotid artery, the left subclavian artery or the proximal vertebral arteries, whereby the aortic arch descends on the left as normal (as opposed to right aortic arch).
A localized circumferential (i.e., bulges on all sides) dilatation or ballooning of a cerebral artery.
Difficulty in performing one or more activities normally performed every day, such as eating, bathing, dressing, grooming, work, homemaking, and leisure.
This term applies to an individual who requires help to bathe more than one part of the body, get in or out of the tub or shower, or who requires total bathing.
This applies to an individual who needs help with dressing or needs to be completely dressed.
This term applies to an individual who requires help transferring to the toilet, cleaning self or who uses bedpan or commode.
Applies to an individual who needs partial or total help with feeding or requires parenteral feeding.
Partial or total incontinence of bowel or bladder.
A failure to collect oocytes after an apparently normal controlled ovarian hyperstimulation cycle for in vitro fertilization.
Femoral torsion, also known as femoral rotation or femoral version, refers to the twist between the proximal and distal parts of the femur on the transverse plane. Femoral anteversion averages between 30-40 degress at birth, and between 8-14 degrees in adults. This term applies if the amount of femoral torsion exceeds this range.
Femoral torsion, also known as femoral rotation or femoral version, refers to the twist between the proximal and distal parts of the femur on the transverse plane. Femoral anteversion averages between 30-40 degress at birth, and between 8-14 degrees in adults. This term applies if the amount of femoral torsion deviates from this range.
Femoral torsion, also known as femoral rotation or femoral version, refers to the twist between the proximal and distal parts of the femur on the transverse plane. Femoral anteversion averages between 30-40 degress at birth, and between 8-14 degrees in adults. This term applies if the amount of femoral torsion is below this range.
Any anomaly of the structure of an organ ofthe endocrine system.
Any anomaly of the function of the endocrine system.
An anomalous response to a test that is designed to probe the function of the endocrine system.
An anomolous response to stimulation by adminstration of the adrenocorticotropic hormone (ACTH). ACTH stimulation normally stimulates the adrenal glands to release cortisol and adrenaline.
An anomalous response to the insulin tolerance test (ITT), in which insulin is administered intravenously and blood glucose and potentially other compounds are measred at intervals. Insulin administration is intended to induce extreme hypoglycemia (bloodgluoce below 40 mg/dl), which in turn induces release of adrenocorticotropic hormone (ACTH) and growth hormone (GH). ACTH induces the adrenal gland to release cortisol, which together with GH opposes the action of insulin on the blood glucose level.
Failure of cortisol levels to respond adequately (by increasing) to the insulin tolerance test (ITT).
An anomalous response to the corticotropin releasing hormone (CRH) stimulation test. Normally,CRH is released by the hypothalamus to induce adrenocorticotropic hormone (ACTH) release by the anterior pituitary. In the stimulation test, CRH is administered intravenously and ACTH and cortisol are measured at intervals.
Failure of cortisol levels to respond adequately (by increasing) to the corticotropin releasing hormone stimulation test.
Failure of growth hormone levels to respond adequately (by increasing) to the insulin tolerance test (ITT).
An anomalous response to the glucagon stimulation test, which like the insulin tolerance test (ITT) stimulates the release of both adrenocorticotropic hormone (ACTH) and growth hormone (GH).
Failure of cortisol levels to respond adequately (by increasing) to the glucagon stimulation test.
Failure of growth hormone levels to respond adequately (by increasing) to the glucagon stimulation test.
An anomalous response to intravenous stimulation by human chorionic gonadotrophin. Stimulation with hCG stimulates testicular Leydig cells to secrete androgens via the Leydig hormone receptors.
An abnormally high increase in insulin levels following a glucagon stimulation test.
A reduced concentration of prealbumin in the blood. Prealbumin, also known as transthyretin, has a half-life in plasma of about 2 days, much shorter than that of albumin. Prealbumin is therefore more sensitive to changes in protein-energy status than albumin, and its concentration closely reflects recent dietary intake rather than overall nutritional status.
The abrupt and transient increase in the annual growth rate normally observed in adolescent individuals does not occur.
Any anomaly of the structure of the humerus.
A decrease in the amount of mineralized bone in one or more vertebrae compared with that expected for a given developmental age.
Any deviation from the normal amount of the thyroid-stimulating hormone (TSH), which is produced by the anterior pituitary gland and stimulates the function of the thyroid gland.
A reduced concentration of inhibin B in the blood.
Any deviation from the normal range of the antimullerian hormone, a peptide produced by the granulosa cells of follicles. Anti-Mullerian hormone (AMH), also known as Mullerian inhibiting substance, is produced by the granulosa cells of small antral follicles of the ovary. AMH has an inhibiting role in the ovary, contributing to follicular arrest. AMH levels in women are low until the age of 8, rise rapidly until puberty and decline steadily from the age of 25 until menopause, when AMH production ceases.
An elevation above the normal range of the antimullerian hormone in the circulation.
A reduction below the normal range of the antimullerian hormone in the circulation.
Any anomaly of the structure of the uterus
An abnormality of the uterus characterized by a normal uterine outline but with an abnormal T-shaped uterine cavity with narrowing cavity due to thickened lateral walls with a correlation 2/3 uterine corpus and 1/3 cervix. The abnormlaity is said to resemble the letter T in hysterosalpingographic imaging.
Reduced width of the cross sectional diameter of the fibula.
A type of bicuspid aortic valve (BAV) characterized by two equal-sized cusps, with no raphe and only two commissures. There is a lateral arrangement of the free edge of the cusps. Note that this differs from some other forms of BAV in which there are three commissures and two of the three cusps are joined by a raphe forming two functional leaflets. This type of BAV often is associated with aortic stenosis.
A type of bicuspid aortic valvue (BAV) characterized by the presence of a single raphe that extends from the commissure to the free edge of the two underdeveloped, conjoint cusps, resulting in two leaflets of unequal size.
A type of bicuspid aortic valve (BAV) characterized by a single raphe between the right and left cusps (RL fusion pattern). This results in two leaflefts with an anterior-posterior leaflet orientation (also called the typical pattern). There is thus one completely developed noncoronary cusp, two completely developed commissures, and one raphe between the underdeveloped left and right coronary cusps extending to the corresponding malformed commissure.
A type of bicuspid aortic valve (BAV) characterized by a single raphe between the right and noncoronary cusps (RN fusion pattern). This results in two leaflets with right-left leaflet orientation (also called the atypical pattern). There is thus one completely developed left cusp, two completely developed commissures, and one raphe between the underdeveloped right and noncoronary coronary cusps extending to the corresponding malformed commissure.
A type of bicuspid aortic valve (BAV) characterized by a single raphe between the left and noncoronary cusps (LN fusion pattern). There is thus one completely developed right cusp, two completely developed commissures, and one raphe between the underdeveloped left and noncoronary coronary cusps extending to the corresponding malformed commissure.
A type of bicuspid aortic valvue (BAV) characterized by the presence of two raphes that each extend from the commissure to the free edge of the two underdeveloped, conjoint cusps. This type of BAV has developmental anlagen of three cusps, commissures, and sinuses, but two commissures are more or less malformed and obliterated, giving rise to a raphe, a fibrous ridge, which extends from the commissure to the free edge of the two underdeveloped, conjoint cusps. This type of BAV is typically associated with a high degree of aortic stenosis.
Decreased cell membrane concentration of thromboxane A2 receptor that is stimulated by thromboxane A2 (TBXA2).
Decreased cell membrane concentration of alpha-2A adrenergic receptor that is stimulated by epinephrine.
Platelets contain contractile proteins (actin and myosin) that induce clot retraction. As the platelets contract, they pull on the surrounding fibrin strands, squeezing serum form the mass, compacting the clot and drawing the ruptured edges of the blood vessel more closely together. Clot retraction is directly proportional to the platelet count and inversely proportional to the fibrinogen concentration.
Abnormal response to convulxin as manifested by reduced or lacking aggregation of platelets upon addition of convulxin.
Abnormal response to collagen-related peptide (CRP) as manifested by reduced or lacking aggregation of platelets upon addition of CRP.
Abnormal response to phorbol myristate acetate (PMA) as manifested by reduced or lacking aggregation of platelets upon addition of PMA.
Abnormal response to calcium Ionophore (such as A23187) as manifested by reduced or lacking aggregation of platelets upon addition of the ionophore.
An abnormality of phosphatidylserine (PS) on activated platelets. PS is normally located on the cytoplasmic face of the resting platelet membrane but appears on the plasma-oriented surface of discrete membrane vesicles that derive from activated platelets. Thrombin, the central molecule of coagulation, is produced from prothrombin by a complex (prothrombinase) between factor Xa and its protein cofactor (factor V(a)) that forms on platelet-derived membranes. This complex enhances the rate of activation of prothrombin to thrombin by roughly 150,000 fold relative to factor X(a) in solution. The negatively charged surface of PS-containing platelet-derived membranes is at least partly responsible for this rate enhancement.
Reduced binding of annexin V to platelet membrane, which is mediated by exposed phosphatidylserine. This can be measured by flow cytometry.
Elevated binding of annexin V to platelet membrane, which is mediated by exposed phosphatidylserine. This can be measured by flow cytometry.
A developmental anomaly of the heart characterizedby the presence of three atria because the left atrium is divided by an abnormal septum.
Applies to a sign or symptom that is provoked or brought about by exposure to a trauma (injury to tissue).
A reduced amount of the enzyme acrosin in the sperm head acrosome. The acrosome is an organelle in the anterior half of the head of spermatozoa, and acrosin is a protease that contributes to the digestation of the zona pellucida in the fertilization process.
Hepatocytes (liver parenchymal cells) exhibit a bloated appearance because of expansion of the cytoplasm by accumulated material.
A deviation from the normal circulating concentration of B-type natriuretic peptide (BNP).
A type of rest posture in an infant that indicated a generalized reduction in muscle tone. The hips are flexed and the legs are abducted to an extent that causes the lateral thigh to rest upon the supporting surface. This posture is said to resemble the legs of a frog.
An abnormal appearance of the liver or any of its components on sonography (ultrasound).
Increased echogenicity of liver tissue on sonography, manifested as an increased amount of white on the screen of the sonography device.
Any deviation from the normal degree of echogenicity of the liver on sonography. Echogenicity refers to the ability of a tissue to reflect or transmit ultrasound waves in the context of surrounding tissues. Whenever there is an interface of structures with different echogenicities, a visible difference in contrast will be apparent on the screen. Based on echogenicity, a structure can be characterized as hyperechoic (white on the screen), hypoechoic (gray on the screen) and anechoic (black on the screen).
Reduced echogenicity of liver tissue on sonography, manifested as an increased amount of black on the screen of the sonography device.
The appearance of the liver in sonographic images is normally uniform. This term applies when there is an irregular or non-uniform appearancde of the liver parenchyma in liver sonography.
An abnormal echotexture visible in liver ultrasound manifesting as a diffuse hyperechoic liver echotexture with multiple, small hypoechoic lesions. The appearance is said to resemble a starry sky (multiple white spots on a dark background).
An abnormality of swallowing characterized by reduced tongue coordination to form bolus after chewing. Food material spreads over the oral cavity instead of being concentrated into a bolus that is easily swallowed.
Vitreous humor of the eye displaying consisting of a vestigial gel in the retrolental space bounded by a convoluted membrane.
Vitreous humor of the eye displaying beaded bundles of irregular diameters.
An abnormal increase in the Arden ratio, which is the ratio between the light peak and the dark trough of the smoothed (physiologic) EOG record.
Decreased platelet cell membrane concentration of glycoprotein Ib.
An atrophic scar (fibrous connective tissue resulting from incomplete healing of a wound) that has stretched (gotten wider), a manifestation of tissue fragility.
A reduction in the thickness of Descemet's membrane.
An decrease in the level of glutamate (Glu) in the brain identified by magnetic resonance spectroscopy (MRS).
Delay or absence of the swallow response, reflexes triggered by the contact the food bolus makes with the anterior faucial pillars.
Reduced bone mineral density of the femur.
Applies to a sign or symptom that is provoked or brought about by eating or drinking foods rich in potassium.
A pregnancy that extends to 42 weeks of gestation or beyond.
A bony projection (spur, osteophyte) originating from the femur, often in the medial femoral neck.
A variant of retinitis pigmentosa in which there is a regional distribution of the retinal degeneration.
A bony projection (spur, osteophyte) originating from the tibia.
A developmental defect characterized by agenesis of one or more vetebral bodies of the cervical spine.
A developmental defect characterized by agenesis of one or more vetebral bodies of the thoracic spine.
Reduced ability to flex (bend) the fingers. This can manifest as incomplete closure of the hand due to weakness in finger flexion.
Head is bent in the posterior direction in a permanent fashion.
An elevated level of circulating N-terminal part of the prohormone of B-type natriuretic peptide (BNP).
An abnormality of the concentration of deoxycorticosterone in the blood. Deoxycorticosterone comprises 11-deoxycorticosterone and 21-deoxycorticosterone.
An abnormality of the concentration of pregnenolone in the blood.
Increased desire for sexual activity on the part of a male.
Reduced desire for sexual activity on the part of a male.
An inflammatory arthritis characterized by purulent synovial fluid with neutrophil accumulation, but with negative cultures.
An abnormal red-brown color of the urine.
In a heliotrope rash, the color of the skin turns to violet, which is the color of the heliotrope flower.
An abnormal morphology of the olfactory bulb (bulbus olfactorius), which is involved in olfaction, i.e. the sense of smell.
Irregularity of the normally smooth surface of the distal metaphysis of the femur.
Any abnormality in the proportion of CD3-positive T cells relative to the total number of T cells.
Abnormal outpouching or sac-like dilatation in the wall of the celiac artery. [HPO:probinson]
Abnormal outpouching or sac-like dilatation in the wall of the superior mesenteric artery . [HPO:probinson]
Abnormal outpouching or sac-like dilatation in the wall of the inferior mesenteric artery . [HPO:probinson]
Body odor characterized by an offensive body odor and the smell of rotting fish due to the excessive excretion of trimethylaminuria (TMA) in the urine, sweat, and breath of affected individuals.
A fish odor in the vaginal area, that is characteristic of bacterial vaginosis (BV), and is due to trimethylamine (TMA).
An anomalous amount or location of cell junction proteins such as plakoglobin or Cx43.
Soft and hard-palate submucous clefts are characterized by bony defects in the midline of the soft and hard palate that are covered by the lining (ie mucous membrane) of the roof of the mouth.
One sided alveolar cleft of the maxilla.
Nonmidline avleolar cleft of the maxilla.
Multiple cysts along the pupillary margin that appear as spherical or tear-drop-shaped pigmented lesions or wrinkled masses emerging from the pupillary border of the iris.
A deviation from the normal circulating concentration of the normal gonadotropin-releasing hormone level secreted from the pituitary gland.
Secretion of gonadotropin-releasing hormone that does not occur in a pulsatile fashion.
Abnormal test result of cardiovascular physiology.
Abnormal results of a MRI for the heart.
Abnormal results of exercise on heart function.
Resting energy expenditure (REE) can be measured with indirect calorimetry using a metabolic cart, which is used to measure the oxygen consumption (VO2) and carbon dioxide production (VCO2).
Abnormal blood test results measuring creatine kinase (CK), CK-MB, troponin (TROPI), myoglobin, and/or cardiac enzymes.
An decreased level of gamma-aminobutyric acid in the brain identified by magnetic resonance spectroscopy (MRS).
A deviation from the normal concentration of dehydroepiandrosterone in the circulation.
Absence of the musculature of the pelvis.
Underdevelopment of the musculature of the pelvis.
Change in normal glycogen storage content.
An elevation in bone density in one or more carpal bones of the hand.
Abnormality of the structure and branching of the dendrites of a neuron.
Presence of a monoclonal immunoglobulin M protein in the serum. [HPO:probinson, PMID:25815903]
An increased amount of desmosine measure in the skin. Desmosine is a cross-linking amino acid formed from lysyl residues in elastin.
Angioma serpiginosum consists of punctate, tightly packed telangiectatic lesions. Characteristic histopathological features are dilated and tortuous capillaries involving the uppermost part of the dermis.
Any anomaly in the process of occular fixation, which is the maintaining of the visual gaze on a single location.
An elevated activity of the enzyme lactate dehydrogenase in serum.
Multiple foci of adipocytes within the testicular interstitium, usually presenting as multiple bilateral ill-defined hyperechoic intratesticular lesions of different sizes but generally with maximum diameter of 4 mm.
An abnormal increase in pressure in the pulmonary veins, usually as a result of left atrial hypertension.
A deviation from the normal concentration of serum bile acid concentration.
Maturation arrest (MA) is defined as germ cells that fail to complete maturation. Uniform MA is characterized by spermatogenic arrest at the same stage of spermatogenesis throughout the seminiferous tubules. MA is subcategorized into early MA, in which only spermatogonia or spermatocytes are found, and late MA, in which spermatids are detected without spermatozoa.
Any deviation from the normal concentration of iInhibins, which are heterodimeric protein hormones secreted by granulosa cells of the ovary in females and Sertoli cells of the testis in males. Inhibins suppress the secretion of pituitary follicle-stimulating hormone.
Fetal masculinization of female external genitalia.
CILD36 is an X-linked recessive disorder characterized by chronic airway disease and recurrent sinopulmonary infections beginning in childhood and caused by defective ciliary function. Affected individuals also have infertility due to defective sperm flagella. About half of patients have laterality defects due to ciliary dysfunction at the embryonic node (summary by Paff et al., 2017). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Noonan syndrome-like disorder with loose anagen hair is characterized by facial features similar to those observed in Noonan syndrome (163950), including hypertelorism, ptosis, downslanting palpebral fissures, low-set posteriorly angulated ears, and overfolded pinnae. In addition, patients display short stature, frequently with growth hormone (GH; see 139250) deficiency; cognitive deficits; relative macrocephaly; small posterior fossa resulting in Chiari I malformation; hypernasal voice; cardiac defects, especially dysplasia of the mitral valve and septal defects; and ectodermal abnormalities, in which the most characteristic feature is the hair anomaly, including easily pluckable, sparse, thin, slow-growing hair (summary by Bertola et al., 2017). Genetic Heterogeneity of Noonan Syndrome-Like Disorder with Loose Anagen Hair NSLH2 (617506) is caused by mutation in the PPP1CB gene (600590) on chromosome 2p23.
NEM11 is an autosomal recessive congenital myopathy characterized by onset of slowly progressive muscle weakness in the first decade. Affected individuals present with gait difficulties due to proximal muscle weakness and atrophy mainly affecting the lower limbs and neck. Muscle biopsy shows nemaline bodies. Some patients may have mild cardiac or respiratory involvement, but they do not have respiratory failure (summary by Miyatake et al., 2017). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM3 (161800).
Early infantile epileptic encephalopathy-51 is an autosomal recessive severe neurodevelopmental disorder characterized by onset of intractable seizures and hypotonia in the first days or weeks of life. Affected individuals have severely delayed psychomotor development and may show abnormal movements. Brain imaging shows nonspecific abnormalities, such as cerebral atrophy, cerebellar atrophy, and delayed myelination. Laboratory studies showed increased lactate, suggesting mitochondrial dysfunction (summary by Ait-El-Mkadem et al., 2017). For a discussion of genetic heterogeneity of EIEE, see 308350.
CRMCC2 is an autosomal recessive multisystem disorder characterized by premature aging, pancytopenia, hypocellular bone marrow, osteopenia, liver fibrosis, and vascular telangiectasia resulting in gastrointestinal bleeding. Brain imaging shows intracranial calcifications and leukodystrophy, which may result in neurologic signs including spasticity, ataxia, or dystonia. Patients may also have retinal telangiectasia (summary by Simon et al., 2016). For a discussion of genetic heterogeneity of CRMCC, see CRMCC1 (612199).
EIEE52 is an autosomal recessive seizure disorder characterized by infantile onset of refractory seizures with resultant delayed global neurologic development that causes intellectual disability and other persistent neurologic abnormalities (summary by Patino et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
CDK13-related disorder, reported in 43 individuals to date, is characterized in all individuals by developmental delay / intellectual disability (DD/ID); nearly all individuals older than age one year display impaired verbal language skills (either absent or restricted speech). Other common findings are recognizable facial features in some individuals, behavioral problems (autism spectrum disorder or autistic traits/stereotypies, attention-deficit hyperactivity disorder), feeding difficulties in infancy, structural cardiac defects, and seizures.
Mild non-BH4-deficient hyperphenylalaninemia (HPANBH4) is an autosomal recessive disorder characterized by increased serum phenylalanine usually detected by newborn screening and associated with highly variable neurologic defects, including movement abnormalities and intellectual disability. Laboratory analysis shows dopamine and serotonin deficiencies in the cerebrospinal fluid, and normal BH4 metabolism. Evidence suggests that treatment with neurotransmitter precursors can lead to clinical improvement or even prevent the neurologic defects if started in infancy (summary by Anikster et al., 2017).
Autoinflammation with arthritis and dyskeratosis is characterized by recurrent fever, widespread skin dyskeratosis, arthritis, elevated biologic markers of inflammation, and mild autoimmunity with a high transitional B-cell level (summary by Grandemange et al., 2016).
Early infantile epileptic encephalopathy-53 is a severe neurodegenerative disorder characterized by onset of intractable seizures in infancy. Affected individuals show hypotonia and very poor or absent global development, resulting in severe intellectual disability and spastic quadriplegia. Some patients may die in childhood (summary by Hardies et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Early infantile epileptic encephalopathy-54 is a severe neurodevelopmental disorder characterized by delayed psychomotor development, early-onset refractory seizures that are often initially febrile but later afebrile, and severe intellectual disability (summary by de Kovel et al., 2016).
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia-13 of the hair/tooth type is characterized by severe oligodontia accompanied by anomalies of hair and skin (Issa et al., 2016).
Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination is a syndromic form of severe to profound intellectual disability with onset of delayed psychomotor development and seizures in infancy. Affected children have hypotonia, feeding difficulties resulting in failure to thrive, and inability to speak or walk, and they tend to show repetitive stereotypic behaviors. Brain imaging shows cerebral atrophy and delayed myelination (summary by Schoch et al., 2017).
Neonatal sclerosing cholangitis is a rare autosomal recessive form of severe liver disease with onset in infancy. Affected infants have jaundice, cholestasis, acholic stools, and progressive liver dysfunction resulting in fibrosis and cirrhosis; most require liver transplantation in the first few decades of life. Cholangiography shows patent biliary ducts, but there are bile duct irregularities (summary by Girard et al., 2016; Grammatikopoulos et al., 2016).
Anauxetic dysplasia is a spondyloepimetaphyseal dysplasia characterized by severe short stature of prenatal onset, very short adult height (less than 1 meter), hypodontia, midface hypoplasia, and mild intellectual disability. Vertebrae are ovoid with concave dorsal surfaces in the lumbar region and show delayed bone maturation. Femoral heads and necks are hypoplastic, as are the iliac bodies. Long bones show irregular mineralization of the metaphyses. The first and fifth metacarpals are short and wide with small, late-ossifying epiphyses and bullet-shaped middle phalanges (summary by Barraza-Garcia et al., 2017). For a discussion of genetic heterogeneity of anauxetic dysplasia, see ANXD1 (607095).
Pseudo-TORCH syndrome-2 is an autosomal recessive multisystem disorder characterized by antenatal onset of intracranial hemorrhage, calcification, brain malformations, liver dysfunction, and often thrombocytopenia. Affected individuals tend to have respiratory insufficiency and seizures, and die in infancy. The phenotype resembles the sequelae of intrauterine infection, but there is no evidence of an infectious agent. The disorder results from inappropriate activation of the interferon (IFN) immunologic pathway (summary by Meuwissen et al., 2016). For a discussion of genetic heterogeneity of PTORCH, see PTORCH1 (251290).
Autosomal recessive cutis laxa type IIC (ARCL2C) is characterized by generalized skin wrinkling with sparse subcutaneous fat and dysmorphic progeroid facial features. Most patients also exhibit severe hypotonia as well as cardiovascular involvement (summary by Van Damme et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100).
Autosomal recessive cutis laxa type IID (ARCL2D) is characterized by generalized skin wrinkling with sparse subcutaneous fat and dysmorphic progeroid facial features. Most patients also exhibit severe hypotonia as well as cardiovascular and neurologic involvement (summary by Van Damme et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100).
MDCCAID is an autosomal recessive form of muscular dystrophy with onset of progressive muscle weakness in early childhood. Almost all patients also have early-onset cataracts, most have intellectual disability of varying severity, and some have seizures (summary by Wiessner et al., 2017 and Osborn et al., 2017).
BTDD is an autosomal dominant disorder characterized by brachycephaly, trichomegaly, and developmental delay. Although it is caused by dysfunction of the ribosome, patients do not have anemia (summary by Paolini et al., 2017).
The presence of a population of T cells with a restricted T cell receptor (TCR) repertoire derived from a limited number of TCR clones.
BDPLT21 is a hematologic disorder characterized by increased risk of bleeding resulting from a functional platelet defect. Platelets have decreased or even absent dense bodies and abnormally enlarged and fused alpha-granules, and they show defective secretion and aggregation responses to agonists. Platelets are usually enlarged, and some patients may have mild to moderate thrombocytopenia (summary by Saultier et al., 2017). For a discussion of genetic heterogeneity of platelet-type bleeding disorders, see BDPLT1 (231200).
IDDGIP is an autosomal dominant syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability with speech delay, and behavioral abnormalities. Most patients have variable additional features, including feeding and gastrointestinal difficulties, high pain threshold and/or hypersensitivity to sound, and dysmorphic features, including mild facial abnormalities, strabismus, and small hands and feet (summary by Jansen et al., 2017).
IDDFSDA is an autosomal recessive severe multisystem disorder characterized by poor overall growth, developmental delay, early-onset seizures, intellectual disability, and dysmorphic features. There is phenotypic variability. The most severely affected patients have a neurodevelopmental disorder with microcephaly, absent speech, and inability to walk, and they require feeding tubes. Some patients have congenital heart defects or nonspecific abnormalities on brain imaging. Less severely affected individuals have mild to moderate intellectual disability with normal speech and motor development (summary by Santiago-Sim et al., 2017).
AMCNMY is an autosomal recessive severe neurologic disorder with onset in utero. Most affected individuals die in utero or are subject to pregnancy termination because of lack of fetal movements and prenatal evidence of contractures of virtually all joints. Those who survive have generalized contractures and hypotonia. The disorder is caused by a neurogenic defect and poor or absent myelin formation around peripheral nerves rather than by a muscular defect (summary by Xue et al., 2017).
Specific granule deficiency-2 is an autosomal recessive immunologic disorder characterized by recurrent infections due to defective neutrophil development. Bone marrow findings include hypercellularity, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. The disorder is apparent from infancy, and most patients die in early childhood unless they undergo hematopoietic stem cell transplantation. Some patients may have additional findings, including delayed development, mild dysmorphic features, and distal skeletal anomalies (summary by Witzel et al., 2017). For a discussion of genetic heterogeneity of SGD, see SGD1 (245480).
NMIHBA is a severe, autosomal recessive, neurodevelopmental, and neurodegenerative disorder characterized by global developmental delay apparent from infancy and profound intellectual disability. Affected individuals have microcephaly with accompanying dysmorphic features, truncal hypotonia, peripheral spasticity, and lack of independent ambulation or speech acquisition. Brain imaging shows variable abnormalities, including cortical atrophy, thin corpus callosum, cerebellar hypoplasia, and delayed myelination (summary by Zollo et al., 2017).
NEDIM is a neurodevelopmental and neurodegenerative disorder characterized by delayed psychomotor development and infantile or childhood onset of hyperkinetic involuntary movements, including chorea and athetosis. The abnormal movements can be severe, sometimes resulting in inability to sit, walk, speak, or eat. Hyperkinetic movements can be exacerbated by specific triggers, such as stress, illness, or high temperature. Some patients have brain abnormalities, such as cerebral atrophy or thin corpus callosum, and some patients may develop seizures (summary by Ananth et al., 2016 and Danti et al., 2017).
IMD52 is an autosomal recessive primary immunodeficiency with variable manifestations, including severe combined immunodeficiency, hematologic autoimmune disorders, progressive lymphopenia and hypogammaglobulinemia, and lymphoproliferation with splenomegaly. Patients develop severe recurrent infections from infancy, and most die without bone marrow transplantation. The variable clinical features result from a defect in T-cell receptor signaling (summary by Keller et al., 2016 and Bacchelli et al., 2017).
Stankiewicz-Isidor syndrome (STISS) is a neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, behavioral disorders, mild craniofacial anomalies, and variable congenital defects of the cardiac and/or urogenital systems (summary by Kury et al., 2017).
Erythrokeratodermia variabilis et progressiva-2 is a genodermatosis characterized by persistent plaque-like or generalized hyperkeratosis and transient red patches of variable size, shape, and location. The severity and dominating features of the disease vary strikingly within families and also during an individual's course of disease. The erythematous component usually prevails in young children, whereas hyperkeratosis is the dominant or sole feature in adults. Some patients with EKVP2 display lesions resembling erythema gyratum repens (summary by Richard et al., 2003). EKVP was previously thought to be separate disorders: erythrokeratodermia variabilis (EKV) and progressive symmetric erythrokeratodermia (PSEK) (van Steensel et al., 2009). For a discussion of genetic heterogeneity of EKVP, see EKVP1 (133200).
Erythrokeratodermia variabilis et progressiva is a rare skin disease. Patients with EKVP3 have normal skin at birth but develop hyperpigmentation and scaling at sites of friction in childhood, with progression to near-confluent corrugated hyperkeratosis, palmoplantar keratoderma, and transient figurate erythema (summary by Boyden et al., 2015). For a discussion of genetic heterogeneity of EKVP, see EKVP1 (133200).
Erythrokeratodermia variabilis et progressiva-4 is characterized by severe lesions of thick scaly skin on the face and genitals, as well as thickened, red, and scaly skin on the hands and feet (summary by Boyden et al., 2017). For a discussion of genetic heterogeneity of EKVP, see EKVP1 (133200).
NDMSBA is an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. Brain imaging may show myelinating abnormalities and white matter lesions consistent with a leukoencephalopathy, as well as structural anomalies, including thin corpus callosum, gyral abnormalities, and cerebral or cerebellar atrophy. Some patients die in early childhood (summary by Falik Zaccai et al., 2017 and Hall et al., 2017).
Intellectual developmental disorder with neuropsychiatric features is an autosomal recessive disorder characterized by moderate intellectual disability, relatively mild seizures, and neuropsychiatric abnormalities, such as anxiety, obsessive-compulsive behavior, and autistic features. Mild facial dysmorphic features may also be present (summary by Srour et al., 2017).
Rahman syndrome is characterized by mild to severe intellectual disability associated with variable somatic overgrowth manifest as increased birth length, height, weight, and/or head circumference. The overgrowth is apparent in infancy and may lessen with time or persist. The phenotype is highly variable; some individuals may have other minor anomalies, including dysmorphic facial features, strabismus, or camptodactyly. The disorder is thought to result from a defect in epigenetic regulation (summary by Tatton-Brown et al., 2017).
Gabriele-de Vries syndrome is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, variable cognitive impairment, often with behavioral problems, feeding problems, some movement abnormalities, and dysmorphic facial features. Affected individuals may also have a variety of congenital abnormalities (summary by Gabriele et al., 2017).
NKX6-2-related disorder is characterized by a spectrum of progressive neurologic manifestations resulting from diffuse central nervous system hypomyelination. At the severe end of the spectrum is neonatal-onset nystagmus, severe spastic tetraplegia with joint contractures and scoliosis, and visual and hearing impairment, all of which rapidly progress resulting in death in early childhood. At the milder end of the spectrum is normal achievement of early motor milestones in the first year of life followed by slowly progressive complex spastic ataxia with pyramidal findings (spasticity with increased muscle tone and difficulty with gait and fine motor coordination) and cerebellar findings (nystagmus, extraocular movement disorder, dysarthria, titubation, and ataxia) with loss of developmental milestones. To date NKX6-2-related disorder has been reported in 25 individuals from 13 families.
EED-related overgrowth is characterized by fetal or early childhood overgrowth (tall stature, macrocephaly, large hands and feet, and advanced bone age) and intellectual disability that ranges from mild to severe. To date, EED overgrowth has been reported in eight individuals.
An orally bioavailable small molecule, targeting the class I phosphatidylinositol 3 kinase (PI3K) family of lipid kinases, with potential antineoplastic activity. Pilaralisib reversibly binds to class 1 PI3Ks in an ATP-competitive manner, inhibiting the production of the secondary messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and activation of the PI3K signaling pathway; this may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis. Dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents including genotoxic agents and receptor tyrosine kinase inhibitors.
A combination preparation of rituximab, a genetically engineered chimeric murine/human immunoglobulin (Ig) G1 kappa monoclonal antibody directed against the CD20 antigen, and the recombinant form of the human enzyme hyaluronidase, with antineoplastic activity. Upon subcutaneous administration of rituximab and hyaluronidase human, the hyaluronidase reversibly depolymerizes the polysaccharide hyaluronan in the subcutaneous tissue. This increases the permeability of the subcutaneous tissue and enhances the absorption of rituximab into the systemic circulation. In turn, rituximab targets and binds to CD20 expressed on tumor cells, and induces tumor cell lysis primarily through the induction of complement dependent cytotoxicity (CDC) and antibody-dependent cell mediated cytotoxicity (ADCC). When administered subcutaneously, hyaluronidase, an endoglycosidase, increases the dispersion and absorption of co-administered drugs. CD20 is expressed on the surface of pre-B and mature B-lymphocytes, and is overexpressed in a variety of B-cell malignancies.
An optimized, second-generation, PEGylated aptamer with antithrombotic property. Egaptivon pegol blocks the binding of von Willebrand factor (vWF), via the A1 domain, and ultra-large vWF multimers to platelets, as well as interferes with the binding of platelet receptor glycoprotein Ib, thus reducing platelet adhesion, aggregation and thrombus growth in arterial beds. Unlike other antiplatelet agents, this aptamer can be readily reversed by binding to a complementary sequence of oligonucleotides, and may therefore offer potential therapeutic benefit in surgery.
A metabolic excess of REACTIVE NITROGEN SPECIES, including NITRIC OXIDE and PEROXYNITRITE, that leads to damaging effects of oxidation and nitration.
Diseases of long duration and generally slow progression. The four main types of noncommunicable diseases are CARDIOVASCULAR DISEASES (e.g., heart attacks and stroke), CANCER, chronic respiratory diseases (e.g., CHRONIC OBSTRUCTIVE PULMONARY DISEASE and ASTHMA) and DIABETES MELLITUS.
EPILEPTIC SEIZURES that are of similar type and age of onset and have other similar features (e.g., clinical course, EEG findings, genetic association and neuropathology).
The reduction in density of the MICROVASCULATURE.
A cluster of chemical dependencies to specific foods or food in general in which there develops a physical craving for these foods.
Various tubular forms of benign tumors of the SWEAT GLAND with glandular differentiation. Common types include syringocystadenoma papilliferum of the head and neck, and hidradenoma papilliferum of the vulva area. Hidradenoma papilliferum may be derived from mammary-like glands of the vulva.
Impaired or delayed impulse conduction between the right and left HEART ATRIA. Advanced interatrial blocks are often associated with arrhythmias (e.g., ATRIAL FLUTTER; and ATRIAL FIBRILLATION), direct conduction block via the Bachmann's bundle and concomitant left atrial enlargement. Syndrome of advanced interatrial block associated with SUPRAVENTRICULAR TACHYCARDIA is referred to as Bayes syndrome.
Bleeding within the CEREBRAL VENTRICLES. It is associated with intraventricular trauma, aneurysm, vascular malformations, hypertension and in VERY LOW BIRTH WEIGHT infants.
Antineoplastic agents containing immunological agents (e.g. MAbs). These pharmacologic preparations inhibit or prevent the proliferation of NEOPLASMS.
The time it takes to reach REM SLEEP. It is typically measured by POLYSOMNOGRAPHY or EEG as a part of various sleep pattern tests (e.g., multiple sleep latency test).
Violence based on gender that results in, or is likely to result in, physical, sexual or mental harm or suffering, including threats of such acts, coercion or arbitrary deprivation of liberty, whether occurring in public or in private life. (From www.who.int/topics/gender_based_violence/en/)
Regulation of the concentration, folding, interactions, and cellular localization of each of the proteins that comprise the PROTEOME.
The dependence of tumor cells on a single oncogenic pathway or protein for their continued proliferation and survival.
Allergic reaction to tree nuts and peanuts, including other LEGUMES, that is triggered by the immune system. It includes co-sensitization to other food (e.g., sesame seed).
Abuse, overuse, or misuse of a substance by ingestion.
Drug formulations or delivery systems intended to discourage the abuse of CONTROLLED SUBSTANCES. These may include physical barriers to prevent chewing or crushing the drug; chemical barriers that prevent extraction of psychoactive ingredients; agonist-antagonist combinations to reduce euphoria associated with abuse; aversion, where controlled substances are combined with others that will produce an unpleasant effect if the patient manipulates the dosage form or exceeds the recommended dose; delivery systems that are resistant to abuse such as implants; or combinations of these methods.
A condition or factor associated with a recipient that makes the use of a specific drug improper or inadvisable.
A condition or factor associated with a recipient that makes the use of a procedure improper or inadvisable.
Chemicals added to pharmacologic preparations, poisonous household goods, and other chemicals to discourage their abuse or consumption.
Movement of internal organs due to physiological processes.
A class of cardiovascular drugs indicated for hypertension and congestive heart failure that simultaneously inhibit both NEUTRAL ENDOPEPTIDASE and ANGIOTENSIN CONVERTING ENZYME. They increase the availability of NATRIURETIC PEPTIDES and BRADYKININ and inhibit production of ANGIOTENSIN II.
Infectious diseases originating in one geographically delineated ecosystem that are carried (by travel or immigration) to another geographically delineated ecosystem by an infected individual, animal, or disease vector.
Conversion of ARGININE residues in proteins into CITRULLINE residues by PEPTIDYLARGININE DEIMINASES.
A tubulin-binding maytansinoid. Ravtansine binds to tubulin at the maytansine-binding site, which disrupts microtubule assembly/disassembly dynamics and inhibits mitosis.
Liver disease lasting six months or more, caused by an adverse effect of a drug or chemical. The adverse effect may be caused by drugs, drug metabolites, chemicals from the environment, or an idiosyncratic response.
An orally available, irreversible, third-generation, mutant-selective epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Upon oral administration, nazartinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. EGF816 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.
An antibody-drug conjugate (ADC) containing a humanized IgG1 monoclonal antibody (MAb) directed against the delta-like protein 3 (DLL3), conjugated to the cytotoxic pyrrolobenzodiazepine (PBD) dimer D6.5 (SC-DR002) via a maleimide-containing linker with an eight-carbon polyethylene glycol spacer and a cathepsin B-cleavable valine-alanine dipeptide, with potential antineoplastic activity. The MAb moiety of rovalpituzumab tesirine selectively binds to DLL3 on tumor cell surfaces. Upon internalization of the ADC, the dipeptide linker is cleaved and D6.5 is released. Then the imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces DNA strand breaks, inhibits DNA replication, leads to G2/M cell cycle arrest, induces cell death, and inhibits the proliferation of DLL3-overexpressing tumor cells. DLL3, a membrane protein that binds to Notch receptors and regulates Notch-mediated signaling and gene transcription, is overexpressed by certain cancers but is rarely expressed by normal, healthy cells.
An orally bioavailable, ATP-competitive, tetrahydroquinazoline (THQ)-based inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. Upon administration, GDC-0349 selectively binds to and inhibits the activity of mTOR, which may result in both the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR, a serine/threonine kinase belonging to the phosphatidylinositol-3 (PI3K) kinase-related kinase (PIKK) family, plays an important role in the PI3K/Akt/mTOR signaling pathway that regulates cell growth and proliferation, and its expression or activity is frequently dysregulated in human cancers.
An orally bioavailable inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) 1 (PARP1) and 2 (PARP2), with potential antineoplastic activity. Upon oral administration, simmiparib selectively binds to PARP and prevents PARP-mediated DNA repair of breaks in single-stranded DNA via the base excision repair pathway. This induces the accumulation of DNA strand breaks, promotes genomic instability, induces G2/M arrest and leads to apoptosis. PARP is activated by single-strand DNA breaks and catalyzes post-translational ADP-ribosylation of nuclear proteins, which signal and recruit other proteins to repair damaged DNA.
An orally bioavailable, allosteric Bcr-Abl tyrosine kinase inhibitor with potential antineoplastic activity. Designed to overcome resistance, ABL001 binds to the Abl portion of the Bcr-Abl fusion protein at a location that is distinct from the ATP-binding domain. This binding results in the inhibition of Bcr-Abl-mediated proliferation and enhanced apoptosis of Philadelphia chromosome-positive (Ph+) hematological malignancies. The Bcr-Abl fusion protein tyrosine kinase is an abnormal enzyme produced by leukemia cells that contain the Philadelphia chromosome.
This syndrome has characteristics of intellectual deficit, a cardiac anomaly, micropenis, hypothyroidism, epileptic seizures and skeletal anomalies. It has been described in two males.
Facial onset sensory and motor neuronopathy is characterised initially by paraesthesia and numbness in the region of the trigeminal nerve distribution, which later progresses to involve the scalp, neck, upper trunk and upper limbs. Onset of motor manifestations occurs later with cramps, fasciculations, dysphagia, dysarthria, muscle weakness and atrophy. This syndrome has been described in four males and appears to be a slowly progressive neurodegenerative disease.
Syndrome with characteristics of various anomalies of the endocrine, cerebral, and skeletal systems resulting in neonatal mortality. Six cases from consanguineous parents have been described. Endocrine anomalies include hypoplasia of the adrenal and pituitary glands. Skeletal anomalies include micromelia, syndactyly, brachydactyly and ulnar deviation of hands. Facial anomalies, such as midface hypoplasia, micrognathia, and a flat and wide nasal bridge, are also observed. The disease is caused by mutations in the ICK gene, encoding an intestinal cell kinase. Transmission is autosomal recessive.
A rare genetic immunological disease reported in a single consanguineous Pakistani family with several affected members presenting with severe bacterial and viral infections, recurrent hepatopathy (portal inflammation, fibrosis) and recurrent, stereotypical febrile episodes, sometimes lasting several days, with encephalopathy and difficult-to-control seizures. Variable cardiac malformations were also reported. Although there were autoimmune lymphoproliferative syndrome (ALPS)-like biological features, clinical ALPS was not present. A homozygous missense mutation in the FADD gene (11q13.3) was found in the family and the disease is thought to follow an autosomal recessive pattern of inheritance.
A potentially fatal neurological disease with characteristics of neuropathological lesions principally involving the brainstem, thalamus and putamen. It has been described in 11 members of one family. Onset occurs during early childhood, typically a few days after a febrile illness. Manifestations include vomiting, seizures, spasticity, language regression, rigidity and abnormal posturing of the head. Residual neurologic impairment (muscle weakness, speech disturbance, intellectual deficit and mood disorders) persists in some patients. The disease is chronic in one out of two cases. The mode of transmission appears to be autosomal dominant with incomplete penetrance.
A genodermatosis with characteristics of the presence of multiple hamartomas of the hair follicle. It has been described in one family so far.
A very rare syndrome that presents with short and sparse scalp hair from birth or the first months of life with no subsequent growth during life. During the first to third decades of life, visual acuity decreases because of progressive macular degeneration, leading in many cases to blindness between the second and fourth decades of life. The hair phenotype does not improve significantly with age, even though diffuse alopecia in infancy can evolve towards short and sparse hair in puberty. Caused by mutations in the CDH3 gene (16q22.1), encoding P-cadherin. P-cadherin is part of adherens junctions in various epithelia including the hair follicular epithelium. Inherited in an autosomal recessive pattern.
Syndrome with characteristics of hypotrichosis, syndactyly, intellectual deficit and early eruption of teeth. It has been described in two patients. The mode of transmission appears to be autosomal recessive.
Syndrome that combines the features of macrostomia or abnormal mouth contour, preauricular tags, uni- or bilateral ptosis and external ophthalmoplegia. It is described in nine members of a Brazilian family. It is a phenotype belonging to the so-called oculoauriculovertebral spectrum, resulting from a branchial arch anomaly. Transmission is autosomal dominant.
A genetic variant of mendelian susceptibility to mycobacterial diseases characterised by Bacille Calmette-Guerin (BCG) infections. The prevalence is unknown. Caused by mutations in the ISG15 gene (1p36.33), which encodes an IFN-alpha/beta inducible, ubiquitin-like intracellular protein. These mutations impair ISG15 secretion by leucocytes, a molecule which plays an essential role as an IFN-gamma-inducing secreted molecule needed for optimal antimycobacterial immunity. Inherited in an autosomal recessive manner.
A rare genetic variant of mendelian susceptibility to mycobacterial disease with characteristics of selective susceptibility to relatively mild infections with bacillus Calmette-Guerin (BCG). The prevalence is unknown. The first infections occur after vaccination with BCG and before the age of 2. No other infectious diseases have been reported. Caused by heterozygous mutations in the IRF8 gene on chromosome 16q24.1 which encodes IRF8, a protein essential for the development of dendritic cells and the differentiation of macrophages and granulocytes. Mutations in the IRF8 gene impair IL-12 secretion by monocytes and dendritic cells. Inherited in an autosomal dominant manner.
A genetic variant of mendelian susceptibility to mycobacterial disease with characteristics of a partial defect in the interferon (IFN)-gamma pathway, leading to mild mycobacterial infections. The prevalence is unknown. First infections occur after the age of 3. Clinical penetrance is incomplete and some patients are asymptomatic while others have very mild clinical manifestations. Caused by heterozygous mutations in the STAT1 gene on chromosome 2q32.2-q32.3 encoding the signal transducer and activator of transcription 1. Two distinct forms have been described: one affecting phosphorylation and the other impairing DNA-binding activity. Transmission is autosomal dominant.
A skeletal dysplasia with distinct facial phenotype, short stature, brachydactyly, clubfoot deformities, cataracts, and microcephaly. It has been described in four patients. Facial features include frontal bossing with a depression over the metopic suture, a narrow nasal root with a beaked nose, and midfacial hypoplasia with prominent eyes. Characteristic radiographic findings are observed (including irregularities of the vertebral bodies, hypoplasia of the odontoid process, short phalanges, coning several epiphyses).
A syndrome of abnormal cortical development with characteristics of severe prenatal polyhydramnios, postnatal microcephaly, lissencephaly, upper limb micromelia, dysmorphic facies (coarse face, hypertrichosis, and short nose with long philtrum), intractable seizures, and early death. Hypoparathyroidism was noted in one case.
A malformative syndrome due to the teratogenic effect of mycophenolate mofetil (MMF), an effective immunosuppressive agent widely used for the prevention of organ rejection after organ transplantation. To date the majority of cases have been offspring of women who received a solid organ transplant. The newborn or fetus generally has external ear anomalies. Cleft lip-palate with micrognathia is frequently observed. Aberrant orofacial cleft has been observed in one case. Ocular anomalies, such as microphthalmia and iris or chorioretinal coloboma are also frequent. Distal limbs anomalies as well as congenital malformations of the heart, kidneys and/or central nervous system may also be observed.
Disease characterised by progressive limb and axial muscle weakness associated with cardiomyopathy and severe respiratory insufficiency during adolescence. The disease manifests during childhood and progresses rapidly. Two patients presented with a rigid spine and one a peripheral neuropathy. Disintegration of Z disks, extensive accumulation of granular debris and larger inclusions and apoptosis of a small fraction of the nuclei distinguish the disease. Caused by a mutation in the BAG3 gene, encoding a protein localised to the Z disk. Transmission is autosomal dominant.
A patterned dystrophy of the retinal pigment epithelium with characteristics of multiple yellowish irregular flecks scattered or interconnected around the macula, simulating what is observed in Stargardt disease. Usually asymptomatic until adulthood when patients present with a slowly progressive loss of vision that often only becomes apparent in old age.
Disease with characteristics of the onset in infancy of cerebellar ataxia, neonatal hypotonia (in some), mild developmental delay and in later life intellectual disability. Less common features include dysarthria, dysmetria and dysmorphic facial features (long face, bulbous nose long philtrum, thick lower lip and pointed chin). Caused by heterozygous disruption of the CAMTA1 gene on chromosome 1p36.
Rare syndrome with characteristics of the combination of polyvalvular heart disease, short stature, facial anomalies and intellectual deficit. Dysplasia may involve the mitral, tricuspidal, aortic and pulmonary valves. Dysmorphic facial anomalies are usually mild, vary among families and include a dolichocephalic face, broad forehead, ptosis, prominent nose, crowded teeth, high-arched palate and posteriorly angulated and everted ears. The severity of short stature is variable, as is the presence of intellectual deficit. The condition seems to be transmitted as an autosomal dominant trait.
A form of ectodermal dysplasia with characteristics of dystrophy of the distal part of the nails and trichodysplasia. It has been described in only one family. Transmission is autosomal recessive.
A slowly progressive Refsum-like disorder associating signs of peripheral neuropathy with late-onset hearing loss, cataract and pigmentary retinopathy that becomes evident during the third decade of life. The syndrome has been described in three patients from a consanguineous family (one brother, one sister and a male cousin). The disease manifests during childhood with pes cavus and tendo-achilles contractures. A disorder of gait, due to ataxia and spasticity, develops during adulthood. Contrarily to Refsum disease, plasmatic phytanic and pristanic acid levels as well as alpha-oxidation enzymatic activity are normal. Transmission is autosomal recessive. The disease was mapped on chromosome 20 (20p11.21-q12).
A benign natural killer (NK) cell lymphoproliferative disease with characteristics of minor abdominal symptoms (abdominal pain, diverticulosis, constipation and reflux) due to NK cell-derived lesions in the mucosal layer of the gastrointestinal tract and often mistaken for NK or T-cell lymphoma.
Syndrome with the association of sensorineural hearing impairment and peripheral neuropathy. It has been described in members from four generations of a Spanish family. The hearing impairment was mild and often asymmetrical. The neuropathy was demyelinating with predominantly sensory involvement but severity was variable ranging from asymptomatic individuals to patients with skin ulcers and osteomyelitis requiring amputation. Caused by mutations in the GJB3 gene (1p34). The syndrome is transmitted in an autosomal dominant manner.
An X-linked mental retardation syndrome belonging to the group of conditions with the association of intellectual deficit with hypotonic facies. Prevalence is unknown but the syndrome was first described in 1982 in five males from two generations of one family (three brothers and two of their maternal uncles). The syndrome has characteristics of the association of microcephaly, spasticity, epilepsy, deafness and severe intellectual deficit. Female carriers show microcephaly and subnormal intelligence. Transmission is X-linked
A rare infectious skin disease characterised by the development of follicular papules with keratin spicules in various parts of the body, predominantly in the face (e.g. nose, eyebrows, auricles), that is due to Polyomavirus infection in immunocompromised patients.
A very rare condition where a maternal riboflavin deficiency causes an infant to present with manifestations similar to those seen in multiple acyl-CoA dehydrogenase (MAD) deficiency such as poor suck, metabolic acidosis and hypoglycaemia, but that resolves completely with oral riboflavin. In the one patient described haploinsufficiency of the human riboflavin transporter (hRFT1) was described in the mother.
Syndrome with characteristics of malformation of the hands and feet, pigmentary skin lesions on the face and scalp and digital fibromatosis. It has been described in 18 females, six of whom came from four different generations of the same family. Phenotypic expression is very heterogeneous. In the majority of patients, the bone dysplasia is limited to the hands and feet but shortening and/or bowing of the bones of the arms and legs has been reported in severe cases. The pigmentary lesions and digital fibromatosis appear a few months after birth. There is evidence that the syndrome is caused by mutation in the FLNA gene. The syndrome is transmitted as an in utero male-lethal X-linked dominant trait, explaining the large number of miscarriages reported in the affected families.
An extremely rare form of primary osteolysis, described in two sisters to date, with characteristics of bilateral osteolysis of the tali, scaphoids, and patellae (accompanied by periarticular swelling and pain) and short fourth metacarpals in the absence of renal disease. Autosomal recessive inheritance has been suggested.
Syndrome with characteristics of infantile symmetrical distal muscle weakness and atrophy of the lower limbs, bilateral anterior polar cataracts and Dandy-Walker malformation. It has been described in two brothers. No sensorineural or cognitive deficits were observed. The karyotypes of the two patients were normal. No mutations were found in the survival motor neurone (SMN), neuronal apoptosis inhibitory protein (NAIP) or androgen receptor genes.
This syndrome has characteristics of nonprogressive spastic paraplegia, retinitis pigmentosa and intellectual deficit. It has been described in two brothers born to consanguineous parents.
Refers to the presence in the serum of one isotype or subclass of immunoglobulin (Ig) that precipitates reversibly below 37°C. The prevalence is unknown. This serological disorder is almost invariably associated with well-known haematological disorders, usually B-cell dyscrasia (multiple myeloma, Waldenstrom macroglobulinaemia, or chronic lymphocytic leukaemia). Type I cryoglobulinaemia is frequently asymptomatic per se but patients may develop acrocyanosis, retinal haemorrhage, Raynaud's phenomenon and arterial thrombosis. The pathogenetic processes in simple cryoglobulinaemia generally appear to be related to those of the underlying lymphoproliferative diseases.
This syndrome has characteristics of severe intellectual deficit, epilepsy, hypoplasia of the terminal phalanges and an anteriorly displaced anus. It has been described in two sisters born to consanguineous parents. The syndrome is transmitted as an autosomal recessive trait and appears to be caused by anomalies in chromosome regions on chromosome 1 and chromosome 14.
The most severe subtype of dystrophic epidermolysis bullosa characterised by generalised cutaneous and mucosal blistering and scarring associated with severe deformities and major extracutaneous involvement. Blisters develop at birth or during the neonatal period and affect all the body as well as the oral and gastrointestinal mucosa. Eye involvement is frequent and includes blepharitis and corneal blisters that can lead to loss of vision. Oesophageal stricture is frequent and result in severe dysphagia. Nearly all patients develop at least one aggressive squamous cell carcinoma. The disease is caused by null mutations within the type VII collagen gene (COL7A1) that usually lead to a lack of functional collagen VII, the main constituent of anchoring fibrils that anchor the basement membrane to the dermis. Transmission is autosomal recessive.
Syndrome is characterised by the combination of sensorineural hearing loss, early greying of scalp hair and adult onset essential tremor. It has been described in three unrelated individuals. Additional family members in each family showed varied expression of these three signs. The syndrome appears to be autosomal dominant with variable penetrance but the causative mutation has not yet been identified.
A complex form of hereditary spastic paraplegia, with onset in childhood or adulthood of progressive spastic paraplegia (with spastic gait, spasticity, lower limb weakness, pes cavus and urinary urgency) associated with the additional manifestation of peripheral sensorimotor neuropathy. The SPG36 phenotype has been mapped to a locus on chromosome 12q23-q24.
A form of hereditary spastic paraplegia with high intrafamilial clinical variability. Characterised in most cases as a pure phenotype with an adult onset (mainly the third to fifth decade of life, but that can present at any age) with progressive gait impairment due to bilateral lower-limb spasticity and weakness as well as very mild proximal weakness and urinary urgency. In some cases, a complex phenotype is also reported with additional manifestations including cognitive impairment, cerebellar ataxia, epilepsy and neuropathy. A faster disease progression is noted in patients with a later age of onset. Caused by mutations in the SPAST gene (2p24-p21), encoding spastin.
A very rare, complex form of hereditary spastic paraplegia characterised by a late-onset, slowly progressive spastic paraplegia associated with mild ataxia and dysarthria, upper extremity involvement (i.e. loss of finger dexterity, dysmetria), and mild cognitive impairment, without the presence of nystagmus. A hypomyelinating leucodystrophy and thin corpus callosum is observed in all cases and psychomotor development is normal or near normal. Caused by mutations in the GJC2 gene (1q41-q42) encoding the gap junction gamma-2 protein.
A rare complex type of hereditary spastic paraplegia with onset, in infancy or childhood of the typical signs of spastic paraplegia (i.e. spastic gait and weakness of the lower limbs) associated with a variety of additional manifestations including upper limb spasticity and weakness, pseudobulbar dysarthria, bladder dysfunction, cerebellar ataxia, cataracts, and cognitive impairment that can progress to dementia. Brain imaging may show thinning of the corpus callosum and mild atrophy of the cerebrum and cerebellum. Caused by mutations in the GBA2 gene (9p13.2) encoding non-lysosomal glucosylceramidase.
A very rare complex type of hereditary spastic paraplegia with characteristics of early-onset spastic paraplegia (with spasticity in the lower extremities that progresses to the upper extremities) associated with developmental and motor delay, mild to moderate cognitive and speech delay, skeletal dysmorphism (e.g. kyphosis and pectus), hypertrichosis and mildly impaired vibration sense. Caused by mutations in the VPS37A gene (8p22) encoding vacuolar protein sorting-associated protein 37A.
A rare complex form of hereditary spastic paraplegia with the onset in early childhood of progressive spastic paraplegia associated with cerebellar signs, short stature, delayed psychomotor development, intellectual disability and less commonly, foot contractures, dysarthria, dysphagia, strabismus and optic hypoplasia. Caused by mutations in the DDHD2 gene (8p11.23) encoding phospholipase DDHD2.
An extremely rare, complex type of hereditary spastic paraplegia, with onset in infancy of pronounced leg spasticity (leading to the inability to walk independently), reduced visual acuity due to optic atrophy and distal wasting of the hands and feet due to an axonal demyelinating sensorimotor neuropathy. Caused by mutations in the TFG gene (3q12.2) encoding protein TFG, which is thought to play a role in ER microtubular architecture and function.
Pulmonary fibrosis - hepatic hyperplasia - bone marrow hypoplasia, also named ""trimorphic syndrome"" (i.e. three inherited morbidities, pulmonary, hepatic and cytopenia), is a rare disease reported in 4 cases to date, manifesting with idiopathic pulmonary fibrosis, hepatic nodular regenerative hyperplasia leading to portal hypertension and thrombocytopenia due to bone marrow hypoplasia. The condition is associated with 100% mortality.
Syndrome that is characterised by generalised keratosis follicularis, severe proportionate dwarfism and cerebral atrophy. It has been described in six males from one family (three boys and three maternal uncles). Generalised alopecia and microcephaly were also present.
A rare complex type of hereditary spastic paraplegia with characteristics of childhood onset of progressive spastic paraplegia associated with optic atrophy (with reduced visual acuity and central scotoma), ophthalmoplegia, reduced upper-extremity strength and dexterity, muscular atrophy in the lower extremities and sensorimotor neuropathy. Caused by mutations in the C12ORF65 gene (12q24.31) encoding probable peptide chain release factor C12ORF65, mitochondrial.
An extremely rare autosomal dominant syndrome described in two families to date and with characteristics of moderate to severe sensorineural hearing loss manifesting during childhood and associated with late-onset dilated cardiomyopathy that generally progresses to heart failure. Caused by mutation in the EYA4 gene.
This syndrome has characteristics of hydroxylysinuria, myoclonic and motor seizures and intellectual deficit. It has been described in a brother and sister born to consanguineous parents and in one unrelated patient.
Syndrome that is characterised by progressive hyalinosis involving capillaries and often arterioles and small veins of the digestive tract and kidneys and idiopathic cerebral calcifications. It has been described in three sisters born to non-consanguineous parents. All three patients also had poikiloderma and greying hair, as well as severe diarrhoea, rectal bleeding, malabsorption and subarachnoid haemorrhage.
The association of absence of the lower lid lacrimal punctum, bilateral ptosis, elevation deficiency of both eyes and mild facial dysmorphism. It has been described in three siblings. The facial dysmorphism includes a narrow and squared forehead, low set and dysplastic ears, a relatively long philtrum, telecanthus, bilateral thick eyebrows and absence of bilateral lower medial eyelashes. The affected patients have no intellectual deficit. The condition seems to be transmitted as an autosomal recessive trait.
This syndrome is characterised by psychomotor delay and severe myopathy (hypotonia, absent tendon reflexes and delayed myelination) from birth, associated with hypermethioninaemia and elevated serum creatine kinase levels. It has been described in three unrelated patients. Transmission appears to be autosomal recessive. Two causative mutations have been identified in the gene encoding S-adenosylhomocysteine hydrolase (SAHH; AHCY), an enzyme involved in methionine metabolism. A methionine-restricted diet, together with creatine supplements, may partly improve the delayed myelination and psychomotor development.
Syndrome with characteristics of the onset of proximal tubulopathy in the first year of life, followed by progressive development during childhood of skin anomalies (erythrocyanosis and abnormal pigmentation), blindness, osteoporosis, cerebellar ataxia, mitochondrial myopathy, deafness and diabetes mellitus. It has been described in two sisters. Their mother had ptosis, muscle weakness and ophthalmoplegia, and southern blot analysis revealed heteroplasmic partial duplication of the mitochondrial DNA. Maternal inheritance of this partial duplication was suggested as the cause of the disease in the two sisters.
Vasculitis has characteristics of inflammatory lesions in the wall of vessels and may be due to different viruses. Pathophysiology is partially misunderstood. However, mechanisms including direct injury by the virus or vascular damage resulting from immune reaction are incriminated. Few viruses are thought to be responsible for vasculitis even though their triggering role is not always easily confirmed. In less common cases, vasculitis affects immunocompetent patients, thus resembling polyarteritis nodosa or cutaneous angiitis.
Syndrome with characteristics of congenital ptosis and posterior fusion of the lumbosacral vertebrae. It has been described in a mother and her two daughters. Serum lactic dehydrogenase activity was elevated in the mother and 1 daughter.
Syndrome that is characterised by the association of progressive sensory ataxia and retinitis pigmentosa. Around 20 cases have been described in the last 50 years. Onset of symptoms usually occurs in childhood. The clinical picture is progressive, homogenous and includes severe sensory ataxia, proprioceptive loss (affecting the iliac crest, upper limbs and thorax), generalised areflexia and diffuse pigmentary retinopathy leading to blindness. Scoliosis, camptodactyly, achalasia and/or gastrointestinal motility dysfunction may also be present. The disease is associated with degeneration of the posterior column of the spinal cord. The causative gene, FLVCR1 (1q32.3), has been identified and localised to the AXPC1 locus (1q32-q31).
Pericardial and diaphragmatic defect is a rare combination of absent pericardium with congenital diaphragmatic defect. It has been reported in less than 20 patients. The absence of pericardic tissue is complete or partial. The diaphragmatic hernia is most often left-sided. Some patients have additional digestive tract malformations. The few reported cases were all sporadic except in a family in which the recurrence of these anomalies in two siblings and the parental consanguinity suggested an autosomal recessive inheritance.
Syndrome with characteristics of severe pre and post-natal growth retardation, microcephaly, intractable feeding difficulties, mild psychomotor retardation, hypotonia and facial dysmorphism. It has been reported in 2 unrelated patients. Facial dysmorphism includes high forehead, broad nasal bridge, thin upper lip, small chin and malformed ears. In addition, the patients presented with skin, iris and hair hypopigmentation and abnormal adipose tissue distribution. The syndrome is caused by an interstitial deletion of paternal origin at 20q13.2q13.3. In the 2 cases, the deletion was approximately 4.5Mb in size and encompassed the GNAS imprinted locus; the loss of the paternally expressed GNAS gene might account for the severe pre and post-natal retardation and intractable feeding difficulties observed in the patients.
This syndrome has characteristics of the combination of endocrine and neuroectodermal abnormalities. These abnormalities include low growth hormone levels, delayed puberty, type II diabetes mellitus, mild intellectual deficit, sensorineural deafness, characteristic facial appearance and alopecia. It has been described in four siblings from Myanmar.
Syndrome with characteristics of variable anomalies of the urinary tract, thumbs and big toes, deafness and nephrosis. It has been described in five brothers. The mode of transmission has not been clearly established but seems to be either autosomal recessive or X-linked dominant.
A syndrome associating neonatal diabetes, congenital hypothyroidism, congenital glaucoma, hepatopathy evolving to fibrosis and polycystic kidneys. It has been described in two siblings. Minor facial anomalies were also observed. Two other families presented incomplete forms of this syndrome. Mutations in GLIS3 encoding for the transcription factor GLI similar 3 seem to be responsible for the syndrome.
In adults over 50 years of age, Fanconi syndrome is frequently related to the urinary secretion of a monoclonal immunoglobulin (Ig) light chain (LC), almost always of the kappa isotype. Prevalence is unknown but around 100 cases have been described in the literature so far. Onset occurs during adulthood: bone pain related to osteomalacia secondary to hypophosphataemia and progressive chronic renal failure are the usual manifestations. These manifestations may precede the diagnosis of a slowly progressive plasma cell disorder by several years. In most cases, the monoclonal kappa light chain is restricted to the V kappa-1 subgroup and bears non-polar or hydrophobic mutations in the variable domain, which induce resistance to cathepsin proteolysis in the proximal tubular cells and promote crystallisation of the variable domain within the endolysosomal compartment.
A very rare syndrome associating bone dysplasia with micromelic dwarfism and eye defects. It has been reported in a father and his son. Bone dysplasia has characteristics of diaphyseal thickening of the long bones, metaphyseal deformation and epiphyseal irregularities. Eye defects consisted of myopia, microspherophakia, lens coloboma and luxation and retinal detachment. The affected patients have normal mental development.
Syndrome that has characteristics of severe antenatal microencephaly, simplified gyration, agenesis of the corpus callosum, absence of basal ganglia (very rare), pontocerebellar atrophy and involvement of the white matter with secondary cerebral atrophy. Congenital cataract, choanal atresia, multiple arthrogryposis and spastic tetraparesis can occur. There is evidence this syndrome is caused by homozygous mutation in the ZNF335 gene on chromosome 20q13.
A teratogenic embryofetopathy that results from maternal exposition to methimazole in the first trimester of pregnancy. Methimazole is an antithyroid thionamide drug used for the treatment of Graves' disease. In the infant, methimazole may result in choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, congenital heart disease (such as ventricular septal defect), renal system malformations and aplasia cutis. Additional features that may be observed include facial dysmorphism (short up slanting palpebral fissures, a broad nasal bridge with a small nose and a broad forehead) and athelia.
Syndrome with characteristics of metaphyseal dysplasia associated with short stature and facial dysmorphism (a beaked nose, short philtrum, thin lips, maxillary hypoplasia, dystrophic yellowish teeth) and acral anomalies (short fifth metacarpals and/or short middle phalanges of fingers two and five). It has been described in several members spanning four generations of a French-Canadian family. The syndrome is likely to be transmitted as an autosomal dominant trait. There is evidence this syndrome is caused by heterozygous duplication resulting in a gain of function in the RUNX2 gene on chromosome 6p21.
A form of neuroacanthocytosis with clinical characteristics of a Huntington's disease-like phenotype with an involuntary hyperkinetic movement disorder, psychiatric manifestations and cognitive alterations, and biochemically by absence of the Kx antigen and by weak expression of the Kell antigens. The disorder is very rare and a few hundred cases are suspected worldwide. About one third of patients present with chorea indistinguishable from that observed in Huntington disease and most patients will develop chorea during the course of the disease. Caused by mutations of the XK gene (Xp21.1) encoding the XK protein, which includes the Kx erythrocyte antigen. Most pathogenic mutations are nonsense mutations or deletions predicting an absent or shortened XK protein lacking the Kell protein-binding site.
A mitochondrial disease described in two unrelated families to date that has a heterogeneous clinical presentation. The syndrome features the association of progressive sensorineural hearing loss with hypertrophic cardiomyopathy and in the majority of cases, encephalomyopathy symptoms such as ataxia, slurred speech, progressive external ophthalmoparesis, muscle weakness, myalgia and exercise intolerance.
A very rare syndrome with characteristics of the association of Mobius syndrome (congenital facial palsy with impaired ocular abduction) with peripheral axonal neuropathy and hypogonadotropic hypogonadism. All of the reported cases were sporadic.
This syndrome has characteristics of severe growth retardation associated with immunodeficiency. Less than 10 cases have been described in literature. Individuals present with typical clinical and biochemical features of Laron syndrome such as post-natal growth retardation, delayed bone age and facial dysmorphism (prominent forehead, hypoplastic nasal bridge), and low serum IGF-1 concentrations with normal or high GH concentrations. Immunodeficiency has manifestations of moderate lymphopenia which leads to recurrent infections of the skin and respiratory tract. The syndrome is due to mutation in the signal transducer and activator of transcription 5b gene (STAT5b). Transmission is autosomal recessive.
A basal subtype of epidermolysis bullosa simplex characterised by generalised or, less frequently, localised acral blistering. 19 cases have been reported to date. Onset of the disease is usually at birth. Milia are rare but atrophic scarring and dystrophic nails usually occur, along with focal keratoderma (palms and soles) and rarely ichthyotic plaques. Extracutaneous involvement is common, including anaemia, growth retardation, oral cavity abnormalities (blisters and erosions, and caries) and constipation. Due to mutations in the KRT14 gene (17q12-q21), encoding keratin 14. Transmission is autosomal recessive.
Syndrome with the association of palmoplantar keratosis and clinodactyly of the fifth finger. Less than 20 cases have been described in the literature so far, and the majority of reported patients were of Mexican origin. Transmission is autosomal dominant.
Infant epilepsy with migrant focal crisis is characterised by early-onset progressive encephalopathy with migrant, continuous myoclonus. Three cases have been reported. The focal continuous myoclonus appeared during the first months of life. Prolonged bilateral myoclonic seizures and generalised tonic-clonic seizures occurred later. Subsequently, a progressive encephalopathy with hypotonia and ataxia appeared. Cortical atrophy was revealed by computed tomography scan and magnetic resonance imaging. The aetiology is unknown.
A severe congenital systemic autoimmune disease characterised by refractory diarrhoea, endocrinopathies, cutaneous involvement and infections. The syndrome usually develops during the first few days or weeks of life and affects exclusively boys. Caused by mutations in the FOXP3 gene (Xp11.23). This gene codes for a forkhead transcription factor which controls the development and function of CD4+ CD25+ regulatory T cells, a major lymphocyte population involved in downregulation of immune responses and self-tolerance. Transmission is X-linked recessive.
Syndrome with characteristics of congenital ichthyosis and hypotrichosis. It has been described in three members of a consanguineous Arab Israeli family. The syndrome is transmitted as an autosomal recessive trait and is caused by a missense mutation in the ST14 gene, encoding the recently identified protease, matriptase on chromosome 11q24. Analysis of skin samples from the patients suggests that this enzyme plays a role in epidermal desquamation.
This syndrome is characterised by severe hypotonia, lactic acidaemia and congenital hyperammonaemia. It has been described in three newborns born to consanguineous parents. Ultrasound examination during the 36th week of pregnancy revealed generalised oedema. Hypertrophic cardiomyopathy and tubulopathy developed within the first week of life and the infants died within the first month. The activities of enzymes in the mitochondrial respiratory chain were reduced in the muscles of the patients. Mutations were identified in the MRPS22 gene on chromosome 3q23, encoding a mitochondrial ribosomal protein.
Syndrome with the association of severe nasal hypoplasia, hypoplasia of the eyes, hyposmia, hypogeusia and hypogonadotropic hypogonadism. It has been described in two males. Additional features included bilateral inguinal hernias, undescended testes, and impaired vision with cataracts and colobomata.
The combination of a propensity for venous thrombosis and seizures has been reported in two unrelated kindreds. Transmission is autosomal recessive. It results from a point mutation of PIGM, which reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol (GPI), leading to partial but severe deficiency of GPI.
Disease characterised by congenital joint contractures (normalising during early childhood), external ophthalmoplegia and proximal muscle weakness. In adult cases, the muscular weakness is progressive. Nineteen affected individuals have been described from one large family. The causative gene, the hereditary inclusion-body myopathy (IBM3) gene, has been mapped to chromosome region 17p13.1. Inheritance is autosomal dominant.
A rare congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X, as well as natural anticoagulants protein C, protein S and protein Z. Other symptoms are often present, including developmental and skeletal anomalies (stippling of the long bones, shortness of the distal phalanges of the fingers, osteoporosis) and pseudoxanthoma elasticum-like syndrome. This disease is an autosomal recessive disorder caused by mutations in the genes encoding either gamma-glutamyl carboxylase (GGCX; 2p12) or the vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1; 16p11.2). These two proteins are necessary for gamma-carboxylation, a postsynthetic modification that allows coagulation proteins to display their proper function.
Syndrome that is characterised by the association of severe hypogammaglobulinaemia, combined T and B cell immunodeficiency, absent lymph node germinal centres, absent tissue plasma cells and hepatic veno-occlusive disease. Mutations in the gene coding PML nuclear body protein Sp110 on chromosome 2q37 were found to be responsible for this association. Transmission is autosomal recessive.
A rare dystonia with a combination of hemidystonia involving one half of the body and hemiatrophy on the same side. Hemidystonia which is sustained and repetitive muscle contractions resulting in abnormal movements or posture involving a single side of the body is preceded in 90% of cases by hemiparesis with a marked improvement before the onset of hemidystonia. Pyramidal syndrome and seizures may also be observed. The syndrome is associated with ipsilateral somatic atrophy. Common causes are childbirth or perinatal complications, delayed sequelae of stroke or head trauma. This syndrome should be differentiated from other causes of primary dystonia or dystonia secondary to inherited disorders or neurodegenerative diseases.
A phenotype of frontonasal dysplasia associated with total alopecia and hypogonadism. Four cases have been described in two families. The frontonasal dysplasia includes coronal craniosynostosis, large skull defect with aplasia of ethmoid and nasal bones, hypertelorism, severely depressed nasal bridge and bifid nasal tip. Affected individuals have mild to moderate intellectual deficit. A homozygous nonsense mutation in the human aristaless-like 4 (ALX4, 11p11.2) gene was identified in both families. The condition is transmitted as an autosomal recessive trait.
A rare craniosynostosis syndrome with characteristics of scaphocephaly, macrocephaly, severe maxillary retrusion, and mild intellectual disability. It has been reported in 11 patients from a three-generation family. The patients had variable dysmorphic features including high forehead, marked midface hypoplasia with severe maxillary retrusion, relative or absolute prognathism, and malocclusion. More severely affected patients were male and had intellectual disability. Molecular analysis revealed a K526E mutation of the fibroblast growth factor receptor 2 gene FGFR2.
A form of familial primary hypomagnesaemia characterised by low serum magnesium values but inappropriate normal urinary magnesium values (i.e. renal hypomagnaesemia). The typical symptoms are weakness of the limbs, vertigo, headaches, seizures, brisk tendon reflexes and mild to moderate psychomotor delay. Less than 20 cases have been described in the literature. Caused by mutations in either CNNM2 (10q23.32) or EGF (4q25). CNNM2 encodes cyclin M2, a ubiquitous protein, predominantly expressed in the thick ascending limb of Henle's loop and in the renal distal convoluted tubule where it is thought to contribute to a magnesium-sensing mechanism.
A form of limb-girdle muscular dystrophy that usually has a childhood onset (but can range from the first to third decade of life) of severe progressive proximal weakness, eventually involving the distal muscles. Some patients may remain ambulatory but most are wheelchair dependant 20 years after onset. Caused by homozygous mutation in the titin gene (TTN).
A form of limb-girdle muscular dystrophy with onset in childhood or adolescence of rapidly progressive proximal limb muscle weakness (particularly affecting the neck, hip girdle, and shoulder abductors), hypertrophy in the calves and quadriceps, ankle contractures and myopia. Caused by homozygous mutation in the gene encoding protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGNT1) on chromosome 1p34.
An extremely rare form of congenital disorder of glycosylation with clinical characteristics in the single reported case of muscle weakness, waddling gait and dilated cardiomyopathy. Caused by homozygous mutation in the DPM3 gene on chromosome 1q22.
A disorder of sex development associated with anomalies in gonadal development that results in genital ambiguity of variable degree ranging from almost female phenotype to almost male phenotype in a patient carrying a male 46,XY karyotype. The disorder is heterogeneous and associated with partial abnormality of both Leydig cell and Sertoli cell function that may result from deletions or point mutations in the SRY gene or dose sensitive sex (NR0B1) locus duplication on the X chromosome. More important are mutations in steroidogenic factor 1 (SF1, NR5A1, Ad4BP). SF-1 is a nuclear receptor and regulator of multiple genes involved in adrenal and gonadal development, steroidogenesis, and the reproductive axis. Therefore, affected patients may also have adrenal insufficiency. Syndromic forms have been associated with WT-1 mutations, which lead to variable testicular dysgenesis and an increased risk of renal abnormalities, namely Wilms tumors or nephrotic syndrome.
This syndrome has characteristics of muscle and heart glycogen deficiency. It has been described in three siblings (two brothers and their younger sister). The older brother died at 10.5 years of age as a result of sudden cardiac arrest and the younger brother presented with hypertrophic cardiomyopathy, abnormal heart rate and blood pressure during exercise, and muscle fatigability. The sister showed no symptoms but a lack of glycogen was identified through muscle biopsy. The syndrome is caused by homozygous missense mutations in the gene encoding muscle glycogen synthase.
A genetically inherited anomaly of glycogen metabolism and a form of glycogen storage disease characterised by fasting hypoglycaemia. It is an extremely rare disease; about 20 cases have been reported in the literature so far. The disease appears in infancy or in early childhood. Patients present with morning fatigue and fasting hypoglycaemia (without hepatomegaly) associated with hyperketonaemia but without hyperalaninaemia or hyperlactacidaemia. After meals, major hyperglycaemia associated with lactate and alanine increase and hyperlipidaemia is observed. Caused by mutations in the GYS2 gene (12p12.2). Transmission is autosomal recessive.
This syndrome is characterised by nonspherocytic haemolytic anaemia due to deficiency of adenosine triphosphatase (ATPase). It has been described in two kindreds, in which at least two generations were affected. The syndrome is probably transmitted as a dominant trait.
This syndrome has characteristics of osteopetrosis, agenesis of the corpus callosum, cerebral atrophy and a small hippocampus. It has been described in a brother and a sister born to nonconsanguineous Caucasian parents. The children died at the ages of 1 and 9 months, respectively. Several additional cases combining axonal dystrophy and osteopetrosis have been described.
An extremely rare genetic disorder with characteristics of the unique association of enchondromatosis with D-2 hydroxyglutaric aciduria. Clinical features include enchondromatosis (with short stature, severe metaphyseal dysplasia and mild vertebral involvement), elevated levels of urinary 2-hydroxyglutaric acid and mild developmental delay.
An extremely rare craniotubular bone dysplasia syndrome described in fewer than 10 patients to date. Clinical manifestations include macrocephaly, frontal bossing, malar hypoplasia, prominent mandible and dental hypoplasia. Other skeletal anomalies include abnormal bone modeling in tubular bones, multiple wormian bones and deformities of chest, pelvis and elbows. An increased risk of fractures is noted.
An extremely rare type of enchondromatosis of very early onset (from neonatal period to infancy) with characteristics of symmetrical multiple enchondromas with metacarpal and phalangeal involvement resulting in short hands and feet, platyspondyly, mild to moderate short stature and intellectual disability.
A rare haematologic disease due to defective platelet function and characterised by mucocutaneous bleeding starting in infancy (around 18 months of age), presenting with prolonged and severe epistaxis, haematoma and bleeding after tooth extraction. Massive menorrhagia and chronic anaemia have also been reported.
An extremely rare genetic combined primary immunodeficiency with characteristics of selective partial lymphopenia (T+/-B+NK+) phenotype and decreased CD3 complex resulting in a variable but usually mild clinical presentation ranging from asymptomatic until adulthood to high susceptibility to infections from early infancy with predominant auto-immune manifestations.
PELVIS is an acronym defining the association of Perineal haemangioma, External genitalia malformations, Lipomyelomeningocele, Vesicorenal abnormalities, Imperforate anus and Skin tag. Eleven cases have been reported.
A rare complex type of hereditary spastic paraplegia with characteristics of early-onset progressive spastic paraplegia presenting in infancy. The disease is associated with optic atrophy, fixation nystagmus and polyneuropathy occurring in late childhood/early adolescence leading to severe motor disability and progressive joint contractures and scoliosis. Caused by mutations in the KLC2 gene (11q13.1), encoding kinesin light chain 2.
An extremely rare genetic congenital heart disease with the presence of atrial septal defect, mostly of the ostium secundum type, associated with conduction anomalies like atrioventricular block, atrial fibrillation or right bundle branch block. There is evidence this disease is caused by heterozygous mutation in the NKX2-5 gene on chromosome 5q35.
A complex form of young-onset Parkinson disease that manifests with pyramidal signs, eye movement abnormalities, psychiatric manifestations (depression, anxiety, drug-induced psychosis, and impulse control disorders), intellectual disability, and other neurological symptoms (such as ataxia and epilepsy) along with classical parkinsonian symptoms. To date, only six families have been reported. Mutations in the genes ATP13A2 (1p36), PLA2G6 (22q13.1), FBXO7 (22q12.3), DNAJC6 (1p31.3), SPG11 (15q13-q15), SPG15 (14q24.1) and SYNJ1 (21q22.2) are associated with this disease. Usually occurs in an autosomal recessive manner however, sporadic cases have also been reported and the majority of these cases are born from consanguineous parents.
An intermediate form of lichen myxedematosus (a form of mucin dermal deposit) which does not meet the criteria for either scleromyxedema or the localized form. Three clinical subtypes have been described and include scleromyxedema without monoclonal gammopathy; localized forms with monoclonal gammopathy and/or systemic symptoms; localized forms with mixed features of the 5 subtypes of localized lichen myxedematosus (discrete form, acral persistent papular mucinosis, self-healing papular mucinosis, papular mucinosis of infancy, and a pure nodular form). The course of atypical lichen myxedematosus is unpredictable because only a few cases have been reported.
A genetic variant of mendelian susceptibility to mycobacterial disease with characteristics of partial deficiency in IFN-gammaR2, leading to impaired response to IFN-gamma and consequently to recurrent moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria. Caused by a heterozygous mutation in the IFNGR2 gene on chromosome 21q22.1-22.2 that encodes the IFN-gamma receptor ligand binding chain 2. The 186delC mutation corresponds to the first mutation conferring an AD partial IFN-gammaR2 deficiency.
A life-threatening rapidly progressive thrombotic disorder affecting mainly neonates and children that has characteristics of purpuric skin lesions and disseminated intravascular coagulation. The disease may progress rapidly to multi-organ failure caused by thrombotic occlusion of small and medium-sized blood vessels. There are two forms of acquired purpura fulminans that are classified according to triggering mechanisms: acute infectious (the most common form) and idiopathic.
Omodysplasia is a rare skeletal dysplasia characterised by severe limb shortening and facial dysmorphism. Two types of omodysplasia have been described: an autosomal recessive or generalised form (also referred to as micromelic dysplasia with dislocation of radius) marked by severe micromelic dwarfism with predominantly rhizomelic shortening of both the upper and lower limbs, and an autosomal dominant form in which stature is normal and shortening is limited to the upper limbs. In total, less than 40 cases of omodysplasia have been described in the literature so far, with the majority of reported cases concerning the autosomal recessive form of the disease. The aetiology remains unknown but a paternally inherited paracentric inversion of 15q13 to q21.3 has been detected in one family.
An X-linked recessive retinal disease with characteristics of fundus hypopigmentation, decreased visual acuity, nystagmus, astigmatism, progressive axial myopia, defective dark adaptation and protanopia. A very rare disease originally reported in a family from Aland Island in the Bothnia Sea. Caused by mutations in the CACNA1F gene. Some mutations in CACNAF1 are associated with CSNB2 suggesting allelism of the two disorders.
A rare autosomal recessively inherited disorder of ketone body metabolism, characterised clinically by episodes of decompensation (often associated with gastroenteritis or fasting) that present with vomiting, lethargy, hepatomegaly, non ketotic hypoglycaemia and in rare cases coma. Patients are mostly asymptomatic between acute episodes. This disease requires an early diagnosis in order to avoid hypoglycaemic crisis that can lead to permanent brain damage or death. Caused by homozygous or compound heterozygous mutation in the HMGCS2 gene on chromosome 1p12.
A teratogenic disorder caused by exposure to retinoid during the first trimester of pregnancy, carrying a risk of fetal malformations of approximately 20%, including central nervous system, craniofacial, ear, thymic, cardiac and limb anomalies.
An extremely severe inborn error of purine biosynthesis with clinical characteristics in the single reported case to date of profound intellectual deficit, epilepsy, dysmorphic features of the knees, elbows and shoulders and congenital blindness. In the one reported case the disease was caused by compound heterozygous mutation in the ATIC gene on chromosome 2q35.
A form of combined T and B cell immunodeficiency with characteristics of severe and persistent cytomegalovirus infection and autoimmune cytopenia. Patients present before the age of one year with severe disseminated cytomegalovirus infection, which can manifest with fever and splenomegaly, and recurrent and severe co-infections including sepsis and pneumonitis. Caused by hypomorphic mutation in the RAG1 gene (11p13). This results in oligoclonal expansion of T cell receptor (TCR) gamma-delta T cells and TCR alpha-beta T cell lymphopenia. Transmission is autosomal recessive.
A rare congenital haemorrhagic disorder characterised by mild to moderate bleeding diathesis with easy bruising, mucosal bleedings, and excessive post-operative haemorrhage due to defect of the platelet P2Y12 receptor resulting in selective impairment of platelet responses to adenosine diphosphate. Caused by mutations in the P2RY12 gene (3q24-q25) which result in the premature truncation of the P2Y12 receptor or in the synthesis of a dysfunctional P2Y12 receptor. Transmission is autosomal recessive.
This syndrome has characteristics of slowly progressive spastic paraplegia, skeletal anomalies of the hands and feet with brachydactyly type E, cone-shaped epiphyses, abnormal metaphyseal phalangeal pattern profile, sternal anomaly (pectus carinatum or excavatum), dysarthria and mild intellectual deficit. It has been reported in five patients, among which there were two sets of identical twins. The significance of the relationship between the twinning process and the condition is not clear. The mode of inheritance is unknown but single-gene transmission seems likely.
This syndrome is characterised by myoclonic epilepsy with generalised spasticity and intellectual deficit. It has been described in six males from two generations of one family. Transmission appears to be X-linked recessive and the syndrome is caused by mutations in the aristaless-related homeobox gene (ARX, Xp22.13).
A distinct form of acute myeloid leukaemia in which this chromosomal anomaly is found de novo or in therapy-related cases. The disease is characterised by frequent extramedullary involvement (mainly hepatomegaly, splenomegaly, lymphadenopathies, cutaneous infiltration, but also gum, bone, central nervous system, testicles involvement), severe coagulation disorder (disseminated intravascular coagulopathy or primary fibrinolysis) and poor prognosis. Morphologically, a blast population with a myelomonocytic stage of differentiation is observed.
An adult-onset movement disorder with characteristics of bradykinesia, dysarthria and muscle rigidity. To date the disease has been observed in seven individuals in one family. Onset of symptoms is in the fourth to fifth decade of life with mild progressive dysarthria and hypokinesia. Dysdiadochokinesia is also present and muscle tone is slightly increased. Dysfunction and changes of the striatal part of the basal ganglia are visible on magnetic resonance imaging. Caused by mutation in the PDE8B gene (5q13.3-q14.1) and transmitted in an autosomal dominant manner with complete penetrance in the investigated family.
A mild form of familial primary hypomagnesaemia characterised by extreme weakness, tetany and convulsions. Secondary disturbances in calcium excretion are observed. Only one large pedigree with 18 affected individuals has been reported in the literature. Caused by mutations in the FXYD2 gene (11q23; mutation p.Gly41Arg) which encodes the gamma subunit of the Na+/K+-ATPase, localised on the basolateral membranes of nephron epithelial cells and expressed in the distal convoluted tubule. Transmission is autosomal dominant.
A subtype of dystrophic epidermolysis bullosa characterised by generalised cutaneous and mucosal blistering that is not associated with severe deformities.The disease manifests at birth or during the neonatal period with generalised blistering. Aplasia cutis congenita can also be observed at birth. The disease is caused by mutations within the type VII collagen gene (COL7A1) that lead to an alteration of function or a reduction in the amounts of collagen VII. This impairs collagen VII assembly into anchoring fibrils which anchor the basement membrane to the underlying dermis. This in turn causes reduced skin resistance to minor trauma. Transmission is autosomal recessive.
The most common form of preaxial polydactyly of fingers, a limb malformation syndrome, with characteristics of duplication of one or more skeletal components of a biphalangeal thumb. Hands are preferentially affected and the right hand is more commonly involved than the left.
A kyphotic deformity of the spine that develops in adolescence. The spinal deformity includes irregularities of the vertebral endplates, the presence of Schmorl's nodes, disc-space narrowing and vertebral wedging. The disease is diagnosed using lateral radiographs of the spine. The thoracic spine is most often affected, but the lumbar spine may also be involved. Analysis of the mode of inheritance in a sample of 90 pedigrees derived from the Siberian population supported an autosomal dominant mode of inheritance with complete penetrance in boys and incomplete penetrance in girls.
House allergic alveolitis is a hypersensitivity pneumonitis resulting from the inhalation of an antigen to which an individual has been previously sensitised in his/her domestic environment.
Cirrhotic cardiomyopathy is the term used to describe a constellation of features indicative of abnormal heart structure and function in patients with cirrhosis. These include systolic and diastolic dysfunction, electrophysiological changes, and macroscopic and microscopic structural changes. Pathogenic mechanisms of cirrhotic cardiomyopathy are multiple and include abnormal membrane biophysical characteristics, impaired beta-adrenergic receptor signal transduction and increased activity of negative-inotropic pathways mediated by cGMP. The exact prognosis remains unclear. The extent of cirrhotic cardiomyopathy generally correlates to the degree of liver insufficiency. Reversibility is possible either pharmacological or after liver transplantation.
Syndrome that is characterised by cerebral gigantism associated with a jaw cyst basal cell naevoid syndrome. It has been reported in less than ten patients from two families. Neurological manifestations include hydrocephalus, ventricular malformation, a cerebellar syndrome, intracranial calcification, oculomotor disturbances and in some cases mild peripheral nervous disorders.
An extremely rare subtype of dystrophic epidermolysis bullosa with characteristics of blistering, which begins acrally and then progressively, spreads toward the trunk. Less than ten cases have been reported to date. Onset is usually at birth or during infancy. The centripetal progression of blister formation is slow and occurs over decades. Healing of blisters is associated with milia formation, atrophic scarring and nail dystrophy. Mucosal involvement is usually absent. The disease is caused by mutations within the type VII collagen gene (COL7A1). Mutations in this gene lead to an alteration in function or to a reduction in the amounts of collagen VII. This impairs its assembly into anchoring fibrils that anchor the basement membrane to the underlying dermis. The disease follows an autosomal recessive pattern of inheritance.
An early-onset form of dysferlinopathy presenting with postnatal hypotonia, weakness in the proximal lower limbs and neck flexor muscles at birth and delayed motor development. To date, two cases have been described. The disease is caused by a mutation in the dysferlin gene (DYSF) coding for a protein involved in membrane repair. Transmission is autosomal recessive.
Syndrome with characteristics of childhood-onset progressive ataxia and cerebellar atrophy. Exercise intolerance with elevated lactate levels and mild intellectual deficit may also be present. The syndrome is caused by ubiquinone deficiency. Mutations in the ADCK3/CABC1 gene on chromosome 1q42 have been detected in affected individuals. This gene is already known to play a role in ubiquinone biosynthesis in yeast. The syndrome is transmitted as an autosomal recessive trait.
A genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) with characteristics of a partial deficiency in IFN-gammaR1, leading to a residual response to IFN-gamma and, consequently, to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria. These infections are recurrent but less severe than those seen in MSMD due to complete IFN-gammaR1 and IFN-gammaR2 deficiencies. Caused by homozygous mutations in the IFNGR1 gene on chromosome 6q23-q24 that encodes the IFN-gamma receptor ligand binding chain. The most common mutation is, by far, I87T. This mutation leads to the expression of IFN-gamma receptors on the cell surface with no signal transduction capacity and they therefore only show a partial response to IFN-gamma. Transmission is autosomal recessive.
A genetic variant of mendelian susceptibility to mycobacterial disease with characteristics of a partial deficiency leading to impaired IFN-gamma immunity and consequently recurrent moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria. Caused by heterozygous mutations in the IFNGR1 gene on chromosome 6q23-q24 that encodes the IFN-gamma receptor ligand binding chain. Microdeletion 818del4 is by far the most common mutation and it corresponds to the first documented hotspot for a microdeletion in the human genome. It leads to the expression of IFN-gamma receptor on the cell surface with no signal transduction and therefore patients only show a partial response to IFN-gamma. Transmission is autosomal dominant.
A genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) with characteristics of a partial deficiency in IFN-gammaR2, leading to a residual response to IFN-gamma and consequently to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria. Only one patient has been reported with this variant to date. Caused by a homozygous mutation (R114C) in IFNGR2 on chromosome 21q22.1-22.2 that encodes the IFN-gamma receptor ligand binding chain. This mutation leads to a residual cellular response to IFN-gamma in terms of IL12p40 production. Transmission is autosomal recessive.
A type of central congenital hypothyroidism with characteristics of low levels of thyroid hormones due to insufficient release of thyroid-stimulating hormone (TSH) caused by pituitary resistance to thyrotropin-releasing hormone (TRH). It may or may not be observed from birth. The clinical manifestations are often subtle, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. More specific symptoms and signs often do not develop until several months of age. Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Caused by mutations in the TRH receptor gene (TRHR; 8q23).
A very rare severe non-syndromic hypochromic anaemia, which is characterised by transfusion-dependent hypochromic, poorly regenerative anaemia, iron overload, resembling non-syndromic sideroblastic anaemia except for increased erythrocyte protoporphyrin levels. It has been reported in 3 siblings to date. Caused by a nonsense heterozygous mutation in the STEAP3/TSAP6 gene. Transmission is most likely recessive with a low expression allele.
A rare mitochondrial disease with characteristics of adult onset of progressive external ophthalmoplegia, exercise intolerance, muscle weakness, manifestations of spinocerebellar ataxia (e.g. impaired gait, dysarthria) and mild motor peripheral neuropathy. Respiratory insufficiency has been reported in some cases.
A rare variant of autosomal recessive congenital ichthyosis. Less than 20 patients are reported in the literature. Large dark scales are present on warmer skin areas such as the trunk, the scalp, and the axillary region. On affected areas, the scales are similar to those observed in lamellar ichthyosis. Caused by specific thermo-sensitive mutations in the TGM1 gene (encoding transglutaminase 1, involved in the cornification of the stratum corneum). Affected skin areas, show a clearly reduced enzyme activity in contrast to healthy skin areas that demonstrate an almost normal enzyme activity. Transmission is autosomal recessive.
A genetic disorder with characteristics of formation of bullae without traumatic origin, alopecia, hyperpigmentation, acrocyanosis, short stature, microcephaly, intellectual deficit, tapering fingers and nail abnormalities. Two families (one of whom was Dutch and the other Italian) have been described up to now, in which only males were affected. Transmission is X-linked recessive. The bullous dystrophy locus has been mapped to Xq26.3 in the Italian family and to Xq27.3 in the Dutch family.
A patterned dystrophy of the retinal pigment epithelium with characteristics of abnormal accumulation of lipofuscin in a butterfly-shaped distribution at the retinal pigment epithelium level. Patients manifest with a slowly progressive loss of vision that often only becomes apparent in old age.
Disease that is characterised by massive enteric protein loss, secretory diarrhoea and intolerance to enteral feeds during the first few weeks of life. It has been described in three male infants. Histochemical studies revealed a complete absence of enterocyte heparan sulphate. All three infants required total parenteral nutrition and repeated albumin infusions.
A glomerular disease with characteristics of severe renal failure and nephrotic syndrome at birth, which rapidly improves in the first weeks of life. The disorder has been described in 15 infants from 5 families originating from Portugal, the Netherlands, Italy, Germany and Morocco. The disease is a congenital disorder where infants present at birth with nephrotic syndrome, acute renal failure (oligoanuria and proteinuria), or both. Respiratory distress and hypertension are also observed during the first days of life. Some degree of dysmorphism may be observed in some cases. Mothers do not show any renal manifestations. Caused by the transplacental transfer of nephritogenic anti-NEP antibodies (IgG1, IgG4 subtypes) from mothers with truncating mutations of the MME gene (3q25.2; coding for NEP), resulting in a functional knockout of MME.
A rare genetic bone development disorder characterised by normal clavicles and symmetrical generalised metaphyseal enchondromas particularly in the distal femur, proximal humerus, and bones of the wrists, hands, and feet. Lesions regress later in life with growth cartilage obliteration. Clinical examination is normal and the course of the disease is benign.
A form of limb-girdle muscular dystrophy presenting in the first or second decades of life with characteristics of slowly progressive proximal and distal muscle weakness and atrophy. Additional manifestations include contractures of the proximal and distal interphalangeal hand joints, rigid spine, restricted pulmonary function and mild cardiomyopathy.
A rare congenital anorectal malformation with characteristics of an egg-like, cystic, mucus-filled mass, composed of intestinal mucosal lining and smooth muscle tissue. Commonly they present in childhood with symptoms of recurrent urinary tract infections, gastroenteritis, obstruction, perianal sepsis and rectal bleeding. Drainage of mucus or pus from the anus is also a typical presenting sign. The majority of malformations are found in the retro-rectal space where they communicate with or are contiguous to the rectum.
A form of familial primary hypomagnesaemia characterised by recurrent urinary tract infections, nephrolithiasis, bilateral nephrocalcinosis, renal magnesium wasting, hypercalciuria and kidney failure. This disease is characterised by impaired tubular reabsorption of magnesium and calcium in the thick ascending limb of Henle's loop due to mutations in CLDN16 (3q27), which encodes claudin-16 (previously known as paracellin 1). A significant residual function is observed in several missense mutations, whereas a complete loss of claudin-16 function appears to be more severe with disease presenting earlier and often progressing to kidney failure at a significantly younger age. Transmission is autosomal recessive.
Autosomal dominant medullary cystic kidney disease is a chronic tubulointerstitial nephropathy, which belongs to a heterogeneous group of inherited tubulo-interstitial nephritis. Less than 60 families affected have been described. Clinical onset and course are insidious. Symptoms typically appear at an average age of 28 years, when the urinary concentrating ability is markedly reduced, producing polyuria and stable low urinary osmolality in the first morning urine and lack of any compensatory effect after endonasal desmopressin. End-stage renal disease typically occurs in the third-fifth decade of life or even later. Two genes have been linked to the disease: MCKD1 (1q21) and MCKD2 (in 16p12, where the gene UMOD, encoding uromodulin or Tamm-Horsfall protein, has been identified as responsible of the disease).
A rare inherited form of cutaneous melanoma with characteristics of development of histologically confirmed melanoma in two first degrees relatives or more relatives in an affected family. It is thought to account for about 10% of all cases of cutaneous melanoma. Tends to occur earlier than non-familial melanoma. The risk of familial melanoma is closely related to a wide range of genetic alterations in susceptibility genes but also appears to be influenced by phenotypic risk factors, such as pigmentation, freckling and sun reactions. Complex interactions between genetic and environmental factors are therefore thought to underlie the disease. The most common high-penetrance susceptibility gene implicated is CDKN2A, accounting for predisposition in approximately 20% of cases. In some affected families, susceptibility is consistent with autosomal dominant inheritance but in most cases, a polygenic mode of inheritance appears likely.
Syndrome with the association of a non-progressive congenital ataxia, severe intellectual deficit, optic atrophy and structural anomalies of the skin vessels. It has been described in five children from a large consanguineous Lebanese family. Short stature and microcephaly were also reported. Transmission is autosomal recessive.
A characteristic selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome is usually mild, commences within 1 week of stopping treatment, resolves spontaneously within 3 weeks, and consists of diverse physical and psychological symptoms, the commonest being dizziness, nausea, lethargy and headache. SSRI reinstatement leads to resolution within 48 hours.
An extremely rare metabolic disorder characterised clinically by skin discolouration, elevated levels of carotene and low levels of vitamin A described in fewer than 5 patients to date. There is evidence that the disease is caused by heterozygous mutation in the BCMO1 gene on chromosome 16q23.
A usually slow-growing epithelial neoplasm with ductal differentiation that arises from the exocrine pancreas and grows mostly within the pancreatic ducts. Grossly, it is characterized by the presence of intraductal masses. Morphologically, there is proliferation of mucin-producing cells within the pancreatic ducts, intraductal accumulation of mucin, and a papillary growth pattern. It may be associated with the presence of an invasive carcinoma. It usually occurs in older patients. Signs and symptoms include epigastric pain, weight loss, jaundice, chronic pancreatitis, and diabetes mellitus.
The association of X-linked Alport syndrome with leiomyomatosis of the esophagus, tracheobronchial tree or female genitals has been reported in more than 30 families. The disease is due to a deletion involving the 5' terminal region of both COL4A5 and COL4A6 (as such, it forms a contiguous gene syndrome). Only the first two exons of COL4A6 are deleted but the extent of COL4A5 gene deletion is variable.
Disease with characteristics of slowly progressive pure cerebellar ataxia associated with dysarthria. It has been described in 53 individuals from 26 families of Canadian origin. The mode of transmission is autosomal recessive. Positional cloning has led to the identification of several gene mutations.
A rare complex type of hereditary spastic paraplegia with characteristics of slowly progressive spastic paraplegia (with walking difficulties appearing at onset at 6-7 years of age) associated with mild intellectual disability. Brain imaging reveals thin corpus callosum, cortical and cerebellar atrophy, and pontine dysraphia. The SPG32 phenotype has been mapped to a locus on chromosome 14q12-q21.
A rare complex type of hereditary spastic paraplegia with characteristics of the onset in childhood/adolescence (ages 2-19) of progressive spastic paraplegia associated mainly with mild to moderate cognitive impairment and developmental delay, cerebellar ataxia, dysarthria, and peripheral neuropathy. Less commonly reported manifestations include skeletal abnormalities (i.e. pes cavus, scoliosis), dyskinesia, dystonia, cataracts, cerebellar signs (i.e. saccadic dysfunction, nystagmus, dysmetria) and bladder disturbances. SPG26 is caused by mutations in the B4GALNT1 gene (12q13.3), encoding Beta-1, 4 N-acetylgalactosaminyltransferase 1.
An extremely rare and complex form of hereditary spastic paraplegia reported in only 4 patients from 2 families to date. The disease has characteristics of spastic paraplegia (presenting between the ages of 1 to 4 years with abnormal gait) associated with microcephaly, amyotrophy, cerebellar signs (e.g. dysarthria) aggressiveness, delayed puberty and mild to moderate intellectual disability. SPG64 is due to mutations in the ENTPD1 gene (10q24.1), encoding ectonucleoside triphosphate diphosphohydrolase 1.
An extremely rare and complex form of hereditary spastic paraplegia with characteristics of onset in infancy of spastic paraplegia (presenting with delayed walking and a scissors gait) associated with short stature and normal cognition. Periventricular deep white matter changes in the corpus callosum are noted on brain imaging. SPG63 is caused by a homozygous mutation in the AMPD2 gene (1p13.3) encoding AMP deaminase 2.
A rare complex form of hereditary spastic paraplegia with characteristics of onset in infancy of spastic paraplegia (presenting with the inability to walk unsupported and a scissors gait) associated with a motor and sensory polyneuropathy with loss of terminal digits and acropathy. SPG61 is due to a mutation in the ARL6IP1 gene (16p12-p11.2) encoding the ADP-ribosylation factor-like protein 6-interacting protein 1.
A form of limb-girdle muscular dystrophy with characteristics of slowly-progressive mainly proximal muscle weakness presenting in early childhood (with difficulties walking and climbing stairs) and mild to severe intellectual disability. Additional manifestations reported include microcephaly, mild increase in thigh or calf muscles and contractures of the ankles.
A form of limb-girdle muscular dystrophy with characteristics of proximal muscle weakness presenting in early childhood (with occasional falls and difficulties in climbing stairs) and a progressive course resulting in loss of ambulation in early adulthood. Muscle atrophy and multiple contractures have also been reported in rare cases.
A form of limb-girdle muscular dystrophy most often with characteristics of an adult onset (but ranging from 11 to 51 years) of mainly proximal lower limb weakness, with difficulties standing on tiptoes being one of the initial signs. Proximal upper limb and distal lower limb weakness is also common as well as atrophy of the quadriceps (most commonly), biceps brachii, and lower leg muscles. However, calf hypertrophy has also been reported in some cases. LGMD2L progresses slowly, with most patients remaining ambulatory until late adulthood.
A form of limb-girdle muscular dystrophy with characteristics of proximal weakness (manifesting as slowness in running) presenting in infancy, along with calf hypertrophy, mild lordosis, scapular winging and normal intelligence or mild intellectual disability.
A form of limb-girdle muscular dystrophy with characteristics of an infantile onset of hypotonia, axial and proximal lower limb weakness (with severe weakness noted after febrile illnesses), cardiomyopathy and normal or reduced intelligence. Hypertrophy of calves, thighs, and triceps have also been reported in some cases.
Syndrome with the association of ptosis, strabismus and ectopic pupils. It has been described in one family (in a mother and three of her children). Transmission is autosomal dominant.
An extremely rare, complex form of hereditary spastic paraplegia with characteristics of slowly progressive spastic paraplegia (with increased muscle tone, decreased strength in the anterior tibial muscles and hyperreflexia in the lower extremities with Babinski sign) presenting in adulthood, associated with Paget disease of the bone. Cognitive decline, dementia and myopathic changes at muscle biopsy have not been reported. Mutations in the VCP gene (9p13.3), encoding transitional endoplasmic reticulum ATPase, have been found to be causative for this disease.
An inherited bone disorder described in 5 families in 1963 and is characterised by localised patella pain and male-to-male transmission.
Syndrome with characteristics of congenital scalp defects and postaxial polydactyly type A. It is an extremely rare condition. The syndrome has variable manifestations with one affected person with both congenital scalp defects and postaxial polydactyly type A, 4 people with scalp defects only and 3 people who had postaxial polydactyly only. Transmission is autosomal dominant.
An acquired biliary tract disease caused by the abusive consumption of ketamine, which results in the fusiform dilatation of the common bile ducts without obstructive lesions or dilatation of the intrahepatic biliary ducts. Possible manifestations of the underlying cholangiopathy include epigastric pain and impaired liver function. Severity of the dilatation appears to correlate with the duration of ketamine consumption and the condition has been reported to be reversible in abstinent patients.
This syndrome is characterised by progressive calcification of the brain and spinal cord, growth retardation, psychomotor anomalies, deafness and anaemia. Renal tubular acidosis was found in one patient. To date, this syndrome has been described in only two patients from one family.
A rare mitochondrial substrate carrier disorder with characteristics of severe muscular hypotonia, seizures beginning in the first year of life and arrested psychomotor development (affecting mainly motor skills). Severe spasticity with hyperreflexia has also been reported. Global cerebral hypomyelination is a characteristic imaging feature of this disease.
An extremely rare otorhinolaryngological malformation, which occurs during early embryogenesis. The disorder has characteristics of a single and on occasions multiple cystic lesion that is most frequently located in the anterior portion of the tongue, either deeply embedded within it or superficially on it. Depending mostly on size and location of the cyst, patients could be asymptomatic or could present a wide array of symptoms, such as varying degrees of respiratory and feeding difficulties, lingual swelling and protrusion, dysphagia, and more rarely, recurrent bleeding or brownish discharge from a lingual sinus.
A multiple congenital anomaly syndrome with characteristics of sacral neural tube defects resulting in tethered cord, atrial and/or ventricular septal heart defects (that are detected in infancy), bilateral symmetrical hyperopia, rapidly progressive early childhood cataracts, bilateral aphakic glaucoma and abnormal facial features (low frontal hairline, small ears, short philtrum, prominent, widely spaced central incisors, and micrognathia). Hypotonia, growth and developmental delay, seizures and joint limitation are also reported.
A rare genetic syndrome that results from the partial duplication of the short arm of chromosome 4. It has a highly variable phenotype, principally with characteristics of psychomotor and language delay, seizures and dysmorphic features such as high forehead with frontal bossing, hypertelorism, prominent glabella, long narrow palpebral fissures, low set ears and short neck. Eye abnormalities (glaucoma, irregular iris pigmentation, hyperopia) have also been reported.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 7. The disorder has a highly variable phenotype that typically manifests with mild to moderate intellectual delay (patients could be in the normal range), speech (particularly expressive language disorders) and distinctive craniofacial features (brachycephaly, broad forehead, straight eyebrows, broad nasal tip, short philtrum, thin upper lip and facial asymmetry). Hypotonia, developmental coordination disorders and various congenital anomalies, such as heart defects, diaphragmatic hernia, renal malformations and cryptorchidism, are frequently presented. Neurological abnormalities (visible on MRI) have been reported.
A rare non-syndromic potentially life-threatening visceral malformation with the absence of normal spleen function, resulting in a primary immunodeficiency. Typically, the condition manifests with severe, recurrent, overwhelming infections (especially pneumococcal sepsis) in otherwise apparently healthy infants. In adults with no history of severe sepsis in infancy, thrombocytosis may be the presenting sign. Howell-Jolly bodies on blood smears and an absent spleen on abdominal ultrasound examination are highly suggestive associated findings. There is evidence this disorder is caused by heterozygous mutation in the RPSA gene on chromosome 3p21.
A rare X-linked intellectual disability syndrome characterised by onset in infancy of delayed motor and speech milestones, generalised tonic-clonic seizures and drop attacks and mild to moderate intellectual disability. Additional less common manifestations include scoliosis, ataxia (resulting in progressive gait disturbance) and bilateral pes planovalgus. Physical appearance is normal with no dysmorphic features reported.
A rare X-linked intellectual disability syndrome characterised by intellectual disability (with severe speech impairment), a myxoedematous appearance, dysmorphic facial features (including large head, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, large ears, wide mouth with everted lower lip and downturned lip corners), low posterior hairline, short, broad neck, marked general hirsutism and abnormal hair whorls, skin changes (e.g. dry skin or hypopigmented spots), widely spaced nipples, obesity, micropenis, onychodystrophy and seizures. Caused by mutation in the UBE2A gene on chromosome Xq24.
A microdeletion syndrome resulting from a partial deletion of the chromosome X. The phenotype is highly variable (depending on length of deletion), but main manifestations include X linked ichthyosis, mild-moderate intellectual deficit, Kallmann syndrome, short stature, chondrodysplasia punctata and ocular albinism. Epilepsy, attention deficit-hyperactivity disorder, autism and difficulties with social communication can be associated.
Syndrome with characteristics of intrauterine growth retardation and intermittent locking of the finger joints. It has been described in two individuals: a mother and her daughter. The mode of transmission is autosomal dominant.
A rare mitochondrial disease with characteristics of exclusive skeletal muscle involvement without clinical evidence of other organ involvement. Disease manifestations are progressive limb weakness, proximal limb muscle atrophy and eye muscle anomalies (e.g. ocular motility restriction, ptosis). Patients may present with lactic acidosis, diffuse myalgia and overall fatigability (particularly during/after physical activities), dysphagia and diminished deep tendon reflexes.
A rare genetic neurometabolic disease with characteristics of severe intellectual disability, spastic quadriparesis, Leber's congenital amaurosis and diabetes insipidus. Additional manifestations include facial dysmorphy (dolichocephalic skull, hypertelorism, deep-set eyes, hypoplastic nares, low-set ears), short stature, truncal hypotonia and axial hypertonia. Brain anomalies (e.g. thin corpus callosum with lack of isthmus and tapered splenium, hypoplasia or atrophy of the optic chiasm, prominent lateral ventricles, diminished white matter) described on magnetic resonance imaging have been reported. High prenatal alpha fetoprotein and intrauterine growth restriction is observed in routine pregnancy examination.
An extremely rare genetic disease reported in only two brothers to date with the combination of craniosynostosis (involving both coronal sutures), congenital absence of the fibula, cryptorchidism, and bilateral simian creases. Intelligence is normal. There have been no further reports in the literature since 1972.
Syndrome with characteristics of cortical blindness, intellectual deficit and polydactyly. This combination was found in three children of first-cousin parents. The facial features included prominent forehead, short nose, long philtrum and microretrognathia. Two of the three children died of acute gastroenteritis. Growth and psychomotor development were severely delayed.
Syndrome that is characterised by the association of marfanoid habitus with visceral diverticula. It has been reported in four adults and two siblings from a consanguineous marriage in two different publications. Paediatric cases also presented with diaphragmatic hernia. Other connective tissue disorders with visceral diverticula have been reported previously, suggesting a relationship between these two conditions.
A very rare slowly progressive form of neurodegeneration with brain iron accumulation (NBIA) with characteristics of classic NBIA features. The clinical manifestations include early-onset spastic-dystonic paraparesis, oromandibular dystonia, dysarthria, parkinsonism, axonal neuropathy, progressive cognitive impairment, complex motor tics, and obsessive-compulsive disorder. The disease is caused by homozygous or compound heterozygous mutation in the COASY gene on chromosome 17q21.
An exceedingly rare severe congenital genetic malformation disorder with characteristics of split hand/split foot, hydronephrosis, and spina bifida. Spinal and skeletal manifestations were thoracolumbar scoliosis, spina bifida (spina bifida occulta or spina bifida cystic), Bochdalek diaphragmatic hernia and radial defects. There have been no further descriptions in the literature since 1987.
A form of limb-girdle muscular dystrophy with characteristics of childhood-onset progressive proximal muscle weakness (leading to reduced ambulation) with myalgia and fatigue, in addition to infantile hyperkinetic movements, truncal ataxia, and intellectual disability. Additional manifestations include scoliosis, hip dysplasia, and less commonly ocular features (e.g. myopia, cataract) and seizures. There is evidence that this disease is caused by homozygous or compound heterozygous mutation in the TRAPPC11 gene on chromosome 4q35.
A form of limb-girdle muscular dystrophy that can present from birth to early childhood, the disease has characteristics of hypotonia, microcephaly, mild proximal muscle weakness (leading to delayed walking and difficulty climbing stairs), mild intellectual disability and epilepsy. Additional manifestations reported in some patients include cataracts, nystagmus, cardiomyopathy, and respiratory insufficiency. The disease is caused by homozygous or compound heterozygous mutation in the GMPPB gene, which encodes the beta subunit of GDP-mannose pyrophosphorylase, on chromosome 3p21.
A form of limb-girdle muscular dystrophy with characteristics of adolescent or early adulthood-onset of progressive proximal muscle weakness and mild facial muscle weakness, with patients becoming wheelchair bound in their fourth to fifth decade of life. Mild, bilateral winged scapula, incomplete right bundle branch block and a sinus rhythm with very rare ventricular extrasystoles have also been reported. There is evidence this may be caused by homozygous mutation in the DES gene on chromosome 2q35.
A rare complex type of hereditary spastic paraplegia with characteristics of progressive spastic paraplegia (presenting in early childhood) associated with delayed motor development, severe intellectual disability and joint contractures. A thin corpus callosum is equally noted on brain magnetic resonance imaging. This disease is caused by a mutation in the ERLIN2 gene (8p11.2) encoding the protein, Erlin-2.
A rare complex type of hereditary spastic paraplegia with characteristics of adult-onset spastic paraplegia associated with spinal pain that radiates to the upper or lower limbs and is related to disk herniation (with minor spondylosis), as well as mild sensorimotor neuropathy. The phenotype has been mapped to a locus on chromosome 6q23-q24.1.
Syndrome that is characterised by primary amenorrhoea, ambiguous external genitalia and bone abnormalities for example hypoplasia of the mandibular condyles, hypoplasia of the maxilla, ulnar dislocation of the radial heads. It has been described in two sisters born to consanguineous parents.
A rare developmental defect during embryogenesis syndrome, with characteristics of normal female karyotype, normal ovaries, male or ambiguous genitalia, urinary tract malformations (ranging from bilateral renal agenesis to mild unilateral hydronephrosis), mullerian duct anomalies (for example complete absence of the uterus and vagina, bicornuate uterus) and imperforate anus.
A form of congenital disorders of N-linked glycosylation with characteristics of distal arthrogryposis (mild flexion contractures of the fingers, deviation of the distal phalanges, swan-neck deformity), retro-micrognathia, general muscle hypotonia, delayed psychomotor development, autism spectrum disorder (speech delay, abnormal use of speech, difficulties in initiating, understanding and maintaining social interaction, limited non-verbal communication), seizures, microcephaly and mild to moderate intellectual disability that becomes apparent with age. The disease is caused by mutations in the gene SLC35A3 (1p21).
A rare Y chromosome number anomaly that affects only males. The disease has characteristics of mild-moderate developmental delay (especially speech), normal to mild intellectual disability, large, irregular teeth with poor enamel, tall stature and acne. Radioulnar stenosis and clinodactyly have also been associated. Boys generally present normal genitalia, while hypogonadism and infertility is frequently reported in adult males.
A rare chromosomal anomaly syndrome, resulting from the partial deletion of the short arm of chromosome X. The disease has principle characteristics of classical Norrie disease (bilateral, severe retinal malformations and opacity of the lens leading to congenital blindness, on occasion associated with progressive sensorineural deafness and intellectual disability), microcephaly, hypotonia, psychomotor and growth delay and moderate to severe mental handicap. Clinical phenotype is highly variable and immunodeficiency, epilepsy and hypogonadism have also been reported.
A rare syndromic intestinal malformation characterised by single or multiple smooth-walled, often tubular, cystic lesions, which on occasion contain ectopic gastric mucosa, located in the thorax (usually in the posterior mediastinum and to the right of the midline) and in the abdomen. Infants usually present with respiratory distress and older patients with heartburn, abdominal pain, vomiting and/or melaena. Vertebral anomalies in the lower cervical spine, with central nervous system involvement, are frequently present and complications, such as bowel obstruction, perforation and intussusception, have also been reported.
An autosomal recessive form of serine deficiency. The infantile disease has clinical characteristics in the few reported cases of congenital microcephaly, psychomotor retardation and intractable seizures.
An autosomal recessive form of serine deficiency. The juvenile disease has clinical characteristics in the few reported cases of absence seizures, moderate developmental delay and behavioral disorders.
A very rare subtype of dystrophic epidermolysis bullosa with characteristics of blistering confined primarily to the hands and feet. The disease usually manifests during infancy with trauma-induced blisters limited to extremities. Healing of blisters is associated with milia formation, atrophic scarring and dystrophic nails. There is no extracutaneous involvement. Caused by mutations within the type VII collagen gene (COL7A1). Mutations in this gene lead to an alteration in function of collagen VII. This impairs its assembly into anchoring fibrils that anchor the basement membrane to the underlying dermis. Transmission is autosomal dominant (acral dominant dystrophic epidermolysis bullosa) or autosomal recessive (acral recessive dystrophic epidermolysis bullosa).
This syndrome, associating familial adult medullary cystic disease with spastic quadriparesis has been described in two cases so far. Renal transplantation was successful in those two patients.
A rare usually aggressive subtype of cutaneous T-cell lymphoma with characteristics of infiltration of the epidermis, dermis or subcutaneous tissue by a clonal population of mature, gamma/delta positive cytotoxic T-cells. Typically it presents with ulcerating plaques on the skin of the extremities, however, frequent involvement of mucosal and extranodal sites (such as the nasal cavity, gastrointestinal tract or lungs) is also observed. Infiltration of lymph nodes, spleen and bone marrow is uncommon and resistance to multilineage chemotherapy is reported.
An aggressive, epidermotropic primary cutaneous T-cell lymphoma. It is characterized by the presence of eruptive papules and nodules, or tumors, which may be localized or disseminated. Morphologically, it is composed of small to medium-sized, or medium-sized to large, CD8-positive T-lymphocytes with pleomorphic or blastic nuclei. Epidermotropism is often pronounced. Angiocentricity and angioinvasion may be present.
Syndrome that is characterised by severe metabolic alterations (insulin resistance or hyperinsulinaemia, hypertriglyceridaemia with low HDL-cholesterol, and altered glucose tolerance) and muscular hypertrophy, myalgia, or weakness. So far, nine cases have been reported. Two of these patients also displayed cardiac conduction disturbances. The syndrome is caused by non-codon mutations at residue 482 of the LMNA gene.
Syndrome that is characterised by renal failure without haematuria, parathyroid hyperplasia and sensorineural deafness. It has been described in five children born to consanguineous parents. The mode of inheritance appears to be autosomal recessive.
This syndrome has characteristics of neonatal diabetes mellitus associated with cerebellar and/or pancreatic agenesis. It has been described in four patients: two sisters and their female cousin belonging to a consanguineous Pakistani family, and one unrelated case (also born to consanguineous parents). Patients also present with facial dysmorphism (a triangular face, small chin, low set ears), flexion contractures of the arms and legs, very little subcutaneous fat and optic nerve hypoplasia. One of the patients had pancreatic agenesis and the others were suspected of having pancreatic hypoplasia. The syndrome is transmitted as an autosomal recessive disorder. It is caused by mutations in the PTF1A gene (10p12.3). Prenatal diagnosis is possible by demonstration of the absence of the cerebellum and severe intra-uterine growth retardation. All patients died in the neonatal period.
Syndrome with the association of intrauterine and postnatal growth retardation, sensorineural deafness and intellectual deficit. The syndrome is extremely rare and only four cases have been reported in the literature so far. Additional clinical features include microcephaly, adiposity, and insulin resistance. Partial gonadal dysfunction and osteoporosis may also be present. Caused by homozygous mutations in the insulin-like growth factor 1 gene (12q22-q24.1). Transmitted as an autosomal recessive trait.
Syndrome with characteristics of a specific natural-killer cell deficiency and susceptibility to viral diseases. It has been described in four children from a large inbred kindred. Three out of the four children reported developed a viral illness. The mode of transmission is most likely autosomal recessive. The causative gene is within a 12-Mb region on chromosome 8p11.23-q11.21.
A very rare hereditary neurological dysmorphic syndrome with characteristics of moyamoya disease, short stature of postnatal onset and stereotypical facial dysmorphism. The syndrome is extremely rare and has been reported in three unrelated families to date, with 10 affected individuals in several generations. These families are not from Japan or Asia, whereas in general the incidence of moyamoya disease is highest in Japan and other Asian countries, in comparison with other parts of the world. Affected patients are all male (X-linked inheritance) and have moyamoya angiopathy (progressive stenosis of the terminal portion of the intracranial internal carotid arteries), short stature, hypergonadotropic hypogonadism and other variable manifestations.. The genetic cause appears to involve Xq28 deletions removing MTCP1/CMC4 and BRCC3 (Xq28) .The specific pathophysiological mechanisms underlying this disorder remain obscure, but appear to involve alteration in DNA repair.
An extremely rare syndromic retinitis pigmentosa characterised by pigmentary retinopathy, diabetes mellitus with hyperinsulinism, acanthosis nigricans, secondary cataracts, neurogenic deafness, short stature mild hypogonadism in males and polycystic ovaries with oligomenorrhoea in females. Inheritance is thought to be autosomal recessive. It can be distinguished from Alstrom syndrome by the presence of intellectual disability and the absence of renal insufficiency. There have been no further descriptions in the literature since 1993.
A rare indolent subtype of clear cell renal carcinoma arising from epithelial cells in the renal cortex. It most frequently manifests with a well-circumscribed, well-encapsulated, unicentric, unilateral, small tumor that typically does not metastasize. Clinically it can present with flank or abdominal pain or hematuria, although most patients are usually asymptomatic at the time of diagnosis.
A rare multiple developmental anomalies syndrome with characteristics of the triad of ectodermal dysplasia (mostly hypohidrotic with dry skin and reduced sweating and sparse, fair scalp hair, eyebrows and eyelashes), severe intellectual disability and variable central nervous system anomalies (cerebellar hypoplasia, dilatation of ventricles, corpus callosum agenesis, Dandy-Walker malformation). Distinct craniofacial dysmorphism with macrocephaly, frontal bossing, midfacial hypoplasia and high arched or cleft palate as well as cryptorchidism, feeding difficulties and hypotonia is associated. There have been no further descriptions in the literature since 1998.
A rare genetic gastroenterological disease characterised by the early onset of chronic diarrhoea, vomiting, anorexia, lactic acidosis, renal insufficiency and hepatic involvement (mild elevation of liver enzymes, steatosis, hepatomegaly). Partial villous atrophy (with eosinophilic infiltration) is observed on intestinal biopsy. Although diarrhoea may resolve, the development of neurologic symptoms (cerebellar ataxia, sensorineural deafness, seizures), retinitis pigmentosa and muscle weakness may complicate disease course and lead to death. There have been no further descriptions in the literature since 1994.
A very rare disease with characteristics of adult-onset unsteady gait and dysarthria, followed by wide-based gait, gait ataxia, ocular dysmetria, intention tremor, scanning speech, hyperreflexia and dysdiadochokinesis.
Spinocerebellar ataxia-38 is an autosomal dominant neurologic disorder characterized by adult-onset of slowly progressive gait ataxia accompanied by nystagmus. Brain MRI shows cerebellar atrophy (summary by Di Gregorio et al., 2014). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
A rare endocrine disease with characteristics of the triad of adult-onset diabetes mellitus, progressive hearing loss (usually presenting in the first decade of life and principally of low to moderate frequencies), and/or juvenile-onset optic atrophy. Psychiatric (i.e. anxiety, depression, hallucinations) and sleep disorders, the only neurologic abnormalities observed in this disease, have been reported in rare cases. There is evidence this disease is caused by heterozygous mutation in the WFS1 gene on chromosome 4p16.
Non-hereditary degenerative ataxia with characteristics of slowly progressive cerebellar syndrome (with ataxia of stance and gait, upper limb dysmetria and intention tremor, ataxic speech, and oculomotor abnormalities), presenting in adulthood (at around 50 years of age), that is not due to a known cause. Extracerebellar symptoms (e.g., decreased vibration sense and absent or decreased ankle reflexes), polyneuropathy and mild autonomic dysfunction may also be present. Mild cognitive impairment has also rarely been reported.
A rare genetic non-syndromic subtype of anorectal malformation, resulting from a developmental defect during embryogenesis. The disorder has characteristics of a wide spectrum of anorectal anomalies lying between the pubococcygeal line and the ischial tuberosity (e.g., rectovestibular and rectovaginal fistulas in the female, recto bulbar fistula in the male and anal agenesis). Patients may present with failure to pass meconium, failure to thrive, and recurrent urinary tract infections.
Isolated congenital megalocornea is a genetic, non-syndromic developmental defect of the anterior eye segment. The disease has characteristics of bilateral enlargement of the corneal diameter and a deep anterior eye chamber, without an elevation in intraocular pressure. It can manifest with mild to moderate myopia as well as photophobia and iridodonesis (due to iris hypoplasia). Associated complications include lens dislocation, retinal detachment, presenile cataract development and secondary glaucoma. There is evidence this disease is caused by mutation in the CHRDL1 gene on chromosome Xq23.
A rare Y chromosome number anomaly with a variable phenotype. The main characteristics of this disorder are moderate to severe intellectual disability, speech delay, hypotonia and mild dysmorphic features, including facial asymmetry, hypertelorism, bilateral low set 'lop' ears, and micrognathia. Skeletal abnormalities (such as skull deformities, radioulnar synostosis, elbow flexion, clinodactyly, brachydactyly) have also been associated with this condition. Genitalia are normal at birth, although hypogonadism and azoospermia has been reported in adults.
A rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 22 with a highly variable phenotype. The disease has characteristics of prematurity, pre and post-natal growth retardation, developmental delay (particularly speech), mild intellectual disability, variable cardiac defects and minor skeletal anomalies (such as clinodactyly). Dysmorphic features include prominent forehead, arched eyebrows, deep set eyes, narrow up slanting palpebral fissures, ear abnormalities, hypoplastic alae nasi, smooth philtrum, down-turned mouth, thin upper lip, retro/micrognathia and pointed chin.
A rare chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 12 with a highly variable phenotype. The disorder has typical characteristics of developmental delay, learning disability, intrauterine and postnatal growth retardation, and mild facial dysmorphism that changes with age. Nasal speech and hypothyroidism are also associated.
A rare genetic non-syndromic cranial nerve and nuclear aplasia malformation. The disease is characterised by the congenital absence of the optic chiasm, resulting from the failure of the optic nerve fibres to cross over and decussate to the contralateral hemisphere, leading to decreased vision, strabismus and congenital nystagmus in infancy.
A benign pituitary gland neoplasm occurring separately from and without involvement of the sella turcica.
A rare subtype of renal cell carcinoma with recurrent genetic abnormalities, harboring rearrangements of the TFE3 (Xp11 t-RCC) or TFEB [t(6;11) t-RCC] genes. The t(6;11) t-RCC has distinctive histologic features of biphasic appearance with larger epitheloid and smaller eosinophilic cells. The symptoms are usually non-specific and include hematuria, flank pain, palpable abdominal mass and/or systemic symptoms of anemia, fatigue and fever.
A sarcoma that arises from the lung. It is related to a bronchus and is often predominantly endobronchial. It is characterized by the proliferation of round and spindle cells within a myxoid stroma. It is associated with the presence of an EWSR1-CREB1 fusion gene.
This syndrome has characteristics of neutropenia with myeloid marrow hypoplasia, monocytopenia and congenital deafness. It has been described in three siblings who suffered recurrent bacterial infections.
Midline cleft of lower lip is a rare anomaly defined as Cleft No. 30 in the Tessier classification. Less than 70 cases have been described worldwide. These cases show a broad variation in severity, ranging from a simple notch in the vermillion to a complete cleft of the lip involving the tongue, the chin, the mandible, the supporting structures of the median of the neck and the manubrium sterni. The tongue is often attached to the cleft alveolar margin (ankyloglossia). Other associated anomalies were described in a number of cases such as absence or underdevelopment of the hyoid bone and/or thyroid cartilage. The only known familial cases were reported in 1936 with 18 affected individuals spanning four generations.
Syndrome with the association of intellectual deficit, microbrachycephaly, hypotelorism, palpebral ptosis, a thin/long face, cleft lip, and anomalies of the lumbar vertebra, sacrum and pelvis. It has been described in two Brazilian sisters. Transmission appears to be autosomal recessive.
Syndrome with the association of microtia, eye coloboma and imperforation of the nasolacrimal duct. So far, it has been described in only one family. The phenotype is associated with the presence of five copies of a copy-number-variable region (CNV) located at 4pter. This is the first example of an amplified CNV being associated with a Mendelian disorder. Transmission is autosomal dominant.
A very rare syndrome consisting of short stature, facial dysmorphism, hypospadias and mixed hearing loss. It has been reported in two brothers. Dysmorphic features include hypertelorism, upper lid coloboma, midface hypoplasia, saddle nose deformity with a midline nasal cleft, thick philtrum and everted lower lip. The two brothers had developmental delay.
The association of auricular abnormalities and cleft lip with or without cleft palate has been described in two siblings. One sibling had postauricular pits, profound myopia, nystagmus and retinal pigment abnormalities. The second sibling was a fetus (gestational age 23 weeks) with severe cleft lip, cleft palate and external ear abnormalities.
A rare type of hereditary spastic paraplegia that can present as either a pure form of spastic paraplegia with lower limb spasticity, hyperreflexia and extensor plantar responses, presenting in childhood or adolescence, or as a complex phenotype associated with additional manifestations including peripheral neuropathy with upper limb amyotrophy, moderate intellectual disability and parkinsonism. Deafness and retinitis pigmentosa were reported in one case. Caused by mutations in the KIF5A gene (12q13.13) encoding the protein kinesin heavy chain isoform 5A.
A form of hereditary spastic paraplegia which usually presents in late adolescence or early adulthood as a pure phenotype of lower limb spasticity with hyperreflexia and extensor plantar responses, as well as mild bladder disturbances and pes cavus. Rarely, it can present as a complex phenotype with additional manifestations including epilepsy, variable peripheral neuropathy and/or memory impairment. Caused by mutations in the NIPA1 gene (15q11.2) encoding the magnesium transporter NIPA1.
This syndrome has characteristics of ichthyosis, unusual facies (small mouth with a thin upper lip and lower lip with a midline groove) and digital anomalies (tapered fingers with a lack of distal flexion creases and wide spacing between the second and third fingers). It has been described in two siblings born to first cousin parents. Transmission appears to be autosomal recessive.
A type of metabolic myopathy described only in two sisters to date, presenting during childhood, and characterised clinically by growth failure, severe muscle weakness, and moderate sensorineural deafness and biochemically by metabolic acidosis, elevated serum pyruvate concentration, hyperalaninaemia and hyperalaninuria. There have been no further descriptions in the literature since 1973.
Syndrome with characteristics of congenital cataract associated with ichthyosis. It has been described in less than ten patients from two unrelated families. Transmission is autosomal recessive.
Syndrome with characteristics of hidrotic ectodermal dysplasia, sensorineural hearing loss and contracture of the fifth fingers. It has been described in brother and sister born to consanguineous parents. The girl also presented with thoracic scoliosis.
The association of hallux varus with short thumbs and first toes (involving the metacarpals, metatarsals, and distal phalanges; the proximal and middle phalanges are of normal length) and abduction of the affected digits. The syndrome has been described in eight affected individuals from four successive generations of one family. Intellectual deficit was observed in all reported individuals. Transmission appears to be autosomal dominant.
Syndrome with characteristics of precocious puberty (due to Leydig cell hyperplasia), progressive spastic paraplegia and intellectual deficit. It has been described in two brothers. The fact that other family members displayed brisk reflexes and dysarthria suggested autosomal dominant inheritance with variable expression.
Syndrome that is characterised by the association of multiple sclerosis with lamellar ichthyosis and haematological anomalies (beta thalassaemia minor and a quantitative deficit of factor VIII-von Willebrand complex). Other clinical manifestations may include eye involvement (optic atrophy, diplopia), neuromuscular involvement (ataxia, pyramidal syndrome, gait disturbance) and sensory disorder. There have been no further descriptions in the literature since 1992.
A complex form of hereditary spastic paraplegia characterised by a spastic paraplegia presenting in adolescence, associated with the additional manifestations of sensorial hearing impairment due to auditory neuropathy and persistent vomiting due to a hiatal or paraoesophageal hernia. The phenotype has been mapped to a locus on chromosome 1p31.1-p21.1.
Syndrome with the association of severe ulnar hypoplasia, absence of fingers two to five and split-foot. It has been described in four males belonging to two generations of the same family. X-linked recessive inheritance is suggested, but autosomal dominant transmission cannot be excluded.
Syndrome with characteristics of intellectual deficit, epilepsy, palpebral conjunctival telangiectasias and diminished serum immunoglobulin antibody, particular facies and a shortened fifth finger. It has been reported in six siblings from a Mexican family. It is probably transmitted as an autosomal recessive trait.
A rare bone developmental disorder belonging to a group of oromandibular limb hypogenesis syndromes. The major anomalies occuring commonly in this group are hypoplasia of the mandible, syndactyly and ectrodactyly, small mouth, cleft palate, hypodontia and facial paralysis. Patients with Charlie M syndrome also present with hypertelorism, absent or conically crowned incisors and variable degrees of hypodactyly of the hands and feet. There have been no further descriptions in the literature since 1976.
Syndrome with characteristics of joint laxity, pectus carinatum and facial dysmorphism (mild frontal bossing, a beaked nose with a low nasal bridge, malar hypoplasia, chubby cheeks, a striking philtrum and arched upper lips). It has been described in two siblings. The mode of transmission is unknown.
A syndrome of multiple congenital anomalies with characteristics of encephalopathy that predominantly occurs in the first year of life and presents as psychomotor delay. Additional features of the disease include moderate dysmorphia, craniosynostosis, dwarfism (due to growth hormone deficiency), intellectual disability, spasticity, ataxia, retinal degeneration and adrenal and uterine hypoplasia. The disease has been described in only two families, with each family having two affected siblings. An autosomal recessive inheritance has been suggested. There have been no further descriptions in the literature since 1991.
Syndrome with characteristics of dysmorphism (including facial asymmetry, arched eyebrows, hypertelorism, broad and flat nasal bridge, microtia, small nose with anteverted nostrils, micrognathia), deafness, cleft palate, male pseudohermaphroditism and growth and psychomotor retardation. It has been described in two siblings. The disease is transmitted as an autosomal recessive trait.
A very rare multiple congenital anomalies syndrome described in four siblings and with characteristics of intellectual deficit, flat face and some skeletal features of Marfan syndrome such as tall stature, dolichostenomelia, arm span larger than height, arachnodactyly of hands and feet, little subcutaneous fat, muscle hypotonia and intellectual deficit.
Syndrome with the association of myoclonus, cerebellar ataxia and sensorineural hearing loss. So far, less than 10 cases have been reported in the literature. The hearing loss was generally diagnosed during childhood or early adulthood and the myoclonic jerks began during adolescence. Transmission appears to be autosomal dominant.
A very rare constellation of multiple anomalies including absence or hypoplasia of the tibia. It has been described in 3 siblings (two males and one female). The syndrome has characteristics of the absence or hypoplasia of the tibia, pre and postaxial polydactyly of the hands and/or feet, syndactyly of the toes, shortening and bowing of other long bones, and retrocerebellar arachnoid cyst. Parental consanguinity reported in the family suggests an autosomal recessive pattern of inheritance.
Syndrome with the association of congenital deafness, short stature, vitiligo, muscle wasting, and achalasia. It has been described in a brother and his sister born to first-cousin parents. It is likely to be transmitted as an autosomal recessive trait.
Syndrome with characteristics of partial duplication of the eyebrows and syndactyly of the fingers and toes. It has been described in three patients (a brother and sister and an isolated case). Skin hyperelasticity, hypertrichosis and long eyelashes and abnormal periorbital wrinkling were also reported in some of the patients. Transmission is autosomal recessive.
An extremely rare inherited form of progressive myoclonic epilepsy with characteristics of progressive myoclonus epilepsy and Lafora bodies, with an early onset (at around 5 years) and a prolonged disease course. Other manifestations include progressive dysarthria, ataxia, cognitive decline, psychosis, dementia, spasticity, dysarthria, myoclonus, and ataxia. The disease course typically extends for several decades. There is evidence the disease is caused by homozygous mutation in the PRDM8 gene on chromosome 4q21.
Syndrome with characteristics of variable spastic paraplegia, bilateral sensorineural deafness, intellectual deficit and progressive nephropathy. It has been described in six members of a family.
Syndrome with characteristics of congenital microcephaly with a sharply sloping forehead, digital anomalies (hallux valgus, syndactyly of the toes, short fifth fingers with a single flexion crease and absence of the distal interphalangeal crease of the fourth finger) and moderate to severe intellectual deficit. Less than 10 patients have been described so far. Linkage analysis has identified a candidate region on chromosome 18 (18p11.2-q12.3). Transmission is autosomal recessive.
An extremely rare neurological disorder presumed to result from maldevelopment of the facial nucleus and/or cranial nerve reported in fewer than 10 families to date. It manifests as non-progressive, isolated, unilateral or bilateral, symmetrical or asymmetrical facial palsy. Involvement of the branches of the facial nerve can be unequal.
Syndrome with characteristics of microcephaly, hypergonadotropic hypogonadism, short stature and facial dysmorphism (a narrow forehead, hypertrophy and fusion of the eyebrows, micrognathia and pinnae abnormalities). It has been described in five siblings (three males and two females) born to consanguineous parents. Additional congenital anomalies present in some of the patients included cubitus valgus and genu valgum. Early tooth loss was also reported. The mode of transmission appears to be autosomal recessive.
Syndrome with characteristics of renal, neurologic and thyroid disease, associated with thrombocytopenia. It has been described in a brother and his sister. Intelligence was normal. It is transmitted as an autosomal recessive trait.
Syndrome with characteristics of nonbullous congenital ichthyosis, intellectual deficit, dwarfism and renal impairment. It has been described in four members of one Iranian family. Transmission is autosomal recessive.
An extremely rare syndrome reported in two siblings of non-consanguineous parents with the association of ocular abnormalities (partial aniridia, congenital glaucoma, telecanthus) with frontal bossing, hypertelorism, unilateral renal agenesis and mild psychomotor delay. There have been no further descriptions in the literature since 1974.
An association reported in a single kindred with characteristics of the variable presence of the following features: anetoderma (macular atrophy of the skin), multiple exostoses and brachydactyly type E. There have been no further descriptions in the literature since 1985.
Syndrome with characteristics of Dandy-Walker malformation, severe intellectual deficit, macrocephaly, brachytelephalangy, facial dysmorphism and severe myopia. Three cases have been described. Transmission appears to be autosomal recessive.
An extremely rare genetic bone disorder with characteristics of the classic features of Joubert syndrome (i.e. malformation of the brainstem causing ataxia, hypotonia, cognitive impairment, and abnormal eye movements), associated with the skeletal anomalies found in Jeune asphyxiating thoracic dystrophy including short-rib dysplasia and narrow thorax causing respiratory failure, short limbs and metaphyseal changes.
Syndrome with characteristics of metaphyseal dysplasia, short-limb dwarfism, mild intellectual deficit and conductive hearing loss, associated with repeated episodes of otitis media in childhood. It has been described in three brothers born to consanguineous Sicilian parents. Variable manifestations included hyperopia and strabismus. The mode of inheritance is autosomal recessive.
An extremely rare autosomal dominant disorder reported in three British families, a Japanese and an Italian family (about 16 cases in total). Onset is usually in the fourth decade of life and the course lasts about 20 years. Reported clinical manifestations include diarrhea, nausea, autonomic failure (areflexia, weakness), neurogenic bladder and urinary infections. The disorder is caused by truncation mutations of the prion protein gene PRNP (20p13) leading to deposition of prion protein amyloid.
An extremely rare autosomal recessive gastroenterological disorder reported in three families so far characterised by meconium ileus without any further stigmata of cystic fibrosis including pulmonary or pancreatic manifestations. Two of the reported patients developed chronic diarrhoea in infancy. Homozygous mutations in the GUCY2C gene (12p12) leading to marked reduction or absence of enzymatic activity of guanylate cyclase 2C were found in the affected patients. The disease was reported to show partial penetrance.
A form of congenital disorders of N-linked glycosylation with characteristics of intellectual disability, delayed motor development, hypotonia and truncal obesity. Additional features include slight facial dysmorphism (hypertelorism, downslanting palpebral fissures, large, low-set ears, hypoplastic nasolabial fold, thin upper lip), hypermobility of the joints and skin laxity. The disease is caused by mutations in the gene MAN1B1 (9q34.3).
A peroxisomal neurodegenerative disorder with characteristics of spasmodic torticollis, dystonic head tremor, intention tremor, nystagmus, hyposmia, and hypergonadotropic hypogonadism with azoospermia. Slight cerebellar signs (left-sided intention tremor, balance and gait impairment) are also noted. Magnetic resonance imaging (MRI) shows bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons and lesions in the occipital region, whereas nerve conduction studies of the lower extremities shows a predominantly motor and slight sensory neuropathy. There is evidence this disease is caused by homozygous mutation in the SCP2 gene on chromosome 1p32.
A life-threatening multi organ disorder which develops in the first months of life, presenting with respiratory distress and proteinuria in the nephrotic range, and leading to severe interstitial lung disease and renal failure. Some patients additionally display cutaneous alterations, ranging from blistering and skin erosions to an epidermolysis bullosa-like phenotype, with toe nail dystrophy and sparse hair. There is evidence this disease is caused by homozygous mutation in the ITGA3 gene on chromosome 17q21.
Syndrome with characteristics of progressive spastic paraplegia, glaucoma and intellectual deficit. It has been described in two families. The second described sibship was born to consanguineous parents. The mode of inheritance is autosomal recessive.
An association of the features of Ehlers-Danlos syndrome and osteogenesis imperfecta, characterised by generalised joint hypermobility and dislocations, skin hyperextensibility and/or translucency, and easy bruising as the predominant clinical features, while being invariably associated with mild signs of osteogenesis imperfecta, including short stature, blue sclera, and osteopenia or fractures.
A congenital malformation syndrome with the association of a permanent camptodactyly of the fingers and the over excretion of taurine in the urine. Camptodactyly mainly affects the little finger, although any finger may be involved. The disease has been described in 17 affected patients from 4 unrelated families. An autosomal dominant inheritance has been suggested. There have been no further descriptions in the literature since 1966.
An extremely rare genetic skin disease characterised by loss of elastin tissue leading to localised areas of flaccid skin and a family history of the disorder.
Very rare syndrome with clinical characteristics of multiple fractures, wormian bones of the skull, dentinogenesis imperfecta and facial dysmorphism (hypertelorism, periorbital fullness). Although the signs are very similar to osteogenesis imperfecta, characteristic cortical defects in the absence of osteopenia and collagen abnormalities are considered to be distinctive. There have been no further descriptions in the literature since 1999.
Syndrome with characteristics of intellectual deficit, marfanoid habitus, microcephaly, and glomerulonephritis. It has been described in two sisters.
A rare chromosomal anomaly syndrome resulting from a partial duplication of the short arm of chromosome 16 and manifesting with a variable phenotype which includes: mild to moderate intellectual deficit and developmental delay (particularly speech), normal growth, short, proximally implanted thumbs and other hand and feet malformations (such as camptodactyly, syndactyly, club feet), mild arthrogryposis and characteristic facies (up slanting, narrow palpebral fissures, hypertelorism, mid face hypoplasia, bulbous nasal tip and low set ears).
A neuromuscular disease with characteristics of progressive symmetric muscle weakness of anterior upper and posterior lower limbs. It has been described in several members of an Australian and an Italian family. The disease usually manifests during the third decade of life with thenar muscle weakness resulting in reduced grip strength. The disease is slowly progressive and generally proceeds with calf muscle weakness appearing during the fourth decade and proximal muscles becoming perceptibly affected in the fifth decade. The disease is due to mutations on the actin-binding domain of the FLNC gene that encodes filamin C, a muscle specific filamin that is also associated with myofibrillar myopathy when mutations affect other parts of the protein. The disease mechanism seems to be linked to an increased actin-binding affinity of filamin C.
A mid-life onset distal myopathy with characteristics of tibialis anterior weakness and progressive respiratory muscle involvement present from the onset of the disease. It has been described in three generations of a family (11 patients). Transmission is autosomal dominant and an anticipation phenomenon is suspected. No genes have yet been identified.
An observable entity of a parameter calculated by types of cardiac output monitor. SVV (%) = (SVmax - SVmin)/SVmean.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the short arm of chromosome 16. The disorder has a highly variable phenotype with typical characteristics of developmental/psychomotor delay (particularly of speech), intellectual disability, autism spectrum disorder, dysmorphic facial features (triangular face, deep set eyes, broad and prominent nasal bridge, up slanting or narrow palpebral features, hypertelorism). Additionally, finger/hand anomalies, short stature, microcephaly and slender build are frequently described.
A rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 17. The disease is characterised by renal cystic disease, maturity onset diabetes of the young type 5 and neurodevelopmental disorders, such as cognitive impairment, developmental delay (particularly of speech), autistic traits and autism spectrum disorder. Mullerian aplasia in females, macrocephaly, mild facial dysmorphism (high forehead, deep set eyes and chubby cheeks) and transient hypercalcaemia has also been reported.
A rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 20. The disorder has a highly variable phenotype with typical characteristics of hypotonia, intellectual disability, cognitive and language deficits (including decreased or absent speech), pre and post-natal growth retardation, feeding difficulties, microcephaly, and malformed hands and feet. Neurodevelopmental disorders (including hyperactivity, social interactive problems and autism spectrum disorder), seizures and dysmorphic facial features (high forehead, hypertelorism, malformed ears, broad nasal bridge, bulbous nasal tip, thin upper lip, small chin) are frequently associated.
A rare chromosomal anomaly syndrome resulting from the partial deletion of the short arm of chromosome 16. The disease has a highly variable phenotype with typical characteristics of developmental delay, mild intellectual disability and autism spectrum disorder. Macrocephaly (apparent by 2 years of age), structural brain malformations, epilepsy, vertebral anomalies and obesity are frequently associated.
A rare subtype of acute myeloid leukaemia with recurrent genetic abnormalities characterised by clonal proliferation of poorly differentiated myeloid blasts in the bone marrow, blood, or other tissues in patients who present the t(6;9)(p23;q34) translocation. Frequently associated with multilineage bone marrow dysplasia, it usually presents with anaemia, thrombocytopenia (often pancytopenia), and other nonspecific symptoms related to ineffective haematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). Basophilia, as well as poor response to chemotherapy, has been reported.
An extremely rare multiple mitochondrial DNA deletion syndrome with markedly decreased deoxyguanosine kinase (DGUOK) activity in skeletal muscle. The disease has a highly variable phenotype. Clinical manifestations include progressive external ophthalmoplegia, mitochondrial myopathy, recurrent rhabdomyolysis, lower motor neuron disease, mild cognitive impairment, sensory axonal neuropathy, optic atrophy, ataxia, hypogonadism and/or parkinsonism.
A mitochondrial disease due to a defect in mitochondrial protein synthesis resulting in deficiency of respiratory chain complexes I, III and IV in the cardiac and skeletal muscle and brain. The disease has characteristics of severe hypertrophic cardiomyopathy, pulmonary hypoplasia, muscle weakness and neurological involvement. Caused by homozygous or compound heterozygous mutation in the AARS2 gene on chromosome 6p21.
A rare autosomal dominant condition characterised by variable expression of microcephaly, ocular disorders including chorioretinopathy, congenital lymphoedema of the lower limbs and mild to moderate intellectual disability. The exact prevalence is not known but the disorder is thought to be rare. The microcephaly is primary, and the severity is variable even within families. Mild to moderate learning difficulties are common. A characteristic facial phenotype including up slanting palpebral fissures, broad nose with rounded tip, anteverted nares, long philtrum with thin upper lip, and prominent chin and ears is well recognised. There is likely to be genetic heterogeneity. However, a significant proportion of cases are caused by mutations in the kinesin family member 11 (KIF11) gene (10q24.1). Inheritance is autosomal dominant with variable expression and reduced penetrance.
An orally available inhibitor of human respiratory syncytial virus (RSV) fusion protein (F protein), with potential antiviral activity. Upon oral administration of GS-5806, this agent specifically binds to F protein on the viral surface, which inhibits RSV F protein-mediated fusion with the host cell membrane and prevents viral entry. This blocks RSV replication, reduces viral load, and decreases the severity of the disease. RSV F protein, a viral surface glycoprotein, plays a key role in RSV fusion with and entry into target cells.
A radioimmunoconjugate, which consists of a monoclonal antibody against the cell-surface antigen CD37 covalently linked, via the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA), to the beta-emitting radioisotope lutetium Lu 177, with potential antineoplastic activity. The antibody moiety of lutetium Lu 177 DOTA-tetulomab binds to CD37 on tumor B-cells. Upon internalization, the radioisotope moiety delivers a cytotoxic dose of beta radiation to CD37-expressing tumor cells. CD37, a transmembrane glycoprotein, is overexpressed in B-cell malignancies.
A small-molecule Toll-like receptor 8 (TLR8) agonist with potential immunostimulating and antineoplastic activities. Motolimod binds to TLR8, present in cutaneous dendritic cells, monocytes/macrophages, and mast cells, which may result in the activation of the central transcription factor nuclear factor-B, the secretion of proinflammatory cytokines and other mediators, and a Th1-weighted antitumoral cellular immune response. Primarily localized to endosomal membranes intracellularly, TLR8, like other TLRs, recognizes pathogen-associated molecular patterns (PAMPs) and plays a key role in the innate immune system.
A member of the synthetic oleanane triterpenoid class of compounds and an activator of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2, Nfe2l2), with potential chemopreventive activity. Upon administration, omaveloxolone activates the cytoprotective transcription factor Nrf2. In turn, Nrf2 translocates to the nucleus, dimerizes with a small Maf protein (sMaf), and binds to the antioxidant response element (ARE). This induces the expression of a number of cytoprotective genes, including NAD(P)H quinone oxidoreductase 1 (NQO1), sulfiredoxin 1 (Srxn1), heme oxygenase-1 (HO1, HMOX1), superoxide dismutase 1 (SOD1), gamma-glutamylcysteine synthetase (gamma-GCS), thioredoxin reductase-1 (TXNRD1), glutathione S-transferase (GST), glutamate-cysteine ligase catalytic subunit (Gclc) and glutamate-cysteine ligase regulatory subunit (Gclm), and increases the synthesis of the antioxidant glutathione (GSH). Nrf2, a leucine zipper transcription factor, plays a key role in the maintenance of redox balance and cytoprotection against oxidative stress.
An orally available inhibitor of porcupine (PORCN), with potential antineoplastic activity. Upon oral administration, WNT974 binds to and inhibits PORCN in the endoplasmic reticulum (ER), which blocks post-translational acylation of Wnt ligands and inhibits their secretion. This prevents the activation of Wnt ligands, interferes with Wnt-mediated signaling, and inhibits cell growth in Wnt-driven tumors. Porcupine, a membrane-bound O-acyltransferase (MBOAT), is required for the palmitoylation of Wnt ligands, and plays a key role in Wnt ligand secretion and activity. Wnt signaling is dysregulated in a variety of cancers.
An orally bioavailable, cyclopamine-derived inhibitor of the Hedgehog (Hh) pathway with potential antineoplastic activity. Specifically, Saridegib binds to and inhibits the cell membrane-spanning G-protein coupled receptor SMO, which may result in the suppression of Hh pathway signaling and a decrease in tumor cell proliferation and survival. SMO is activated upon binding of Hh ligand to the cell surface receptor Patched (PTCH); inappropriate activation of Hh signaling and uncontrolled cellular proliferation may be associated with SMO mutations. The Hh signaling pathway plays an important role in proliferation of neuronal precursor cells in the developing cerebellum and other tissues.
An orally bioavailable inhibitor of the human epidermal growth factor receptor tyrosine kinase ErbB-2 (also called HER2) with potential antineoplastic activity. Tucatinib selectively binds to and inhibits the phosphorylation of ErbB-2, which may prevent the activation of ErbB-2 signal transduction pathways, resulting in growth inhibition and death of ErbB-2-expressing tumor cells. ErbB-2 is overexpressed in a variety of cancers and plays an important role in cellular proliferation and differentiation.
A small-molecule pyridylsulfonamide inhibitor of phosphatidylinositol 3-kinase (PI3K) with potential antineoplastic activity. Omipalisib binds to and inhibits PI3K in the PI3K/mTOR signaling pathway, which may trigger the translocation of cytosolic Bax to the mitochondrial outer membrane, increasing mitochondrial membrane permeability and inducing apoptotic cell death. Bax is a member of the proapoptotic Bcl2 family of proteins. PI3K, often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival.
A receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic and anti-angiogenic activities. Upon administration, anlotininib targets multiple RTKs, including vascular endothelial growth factor receptor type 2 (VEGFR2) and type 3 (VEGFR3). This agent may both inhibit angiogenesis and halt tumor cell growth.
An orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Uprosertib binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents.
A benzyl styryl sulfone analog, and a phosphate ester prodrug of ON 013100, with potential antineoplastic activity. Upon hydrolysis, briciclib is converted to ON 013100, which blocks cyclin D mRNA translation and decreases protein expression of cyclin D. This may induce cell cycle arrest and apoptosis in cancer cells overexpressing cyclin D and eventually decrease tumor cell proliferation. Cyclin D, a member of the cyclin family of cell cycle regulators, plays a key role in cell cycle division and is often overexpressed in a variety of hematologic and solid tumors and is correlated with poor prognosis. suppresses cyclin D1 accumulation in cancer cells.
An orally bioavailable, pan fibroblast growth factor receptor (FGFR) inhibitor with potential antineoplastic activity. Upon oral administration, erdafitinib binds to and inhibits FGFR, which may result in the inhibition of FGFR-related signal transduction pathways and thus the inhibition of tumor cell proliferation and tumor cell death in FGFR-overexpressing tumor cells. FGFR, upregulated in many tumor cell types, is a receptor tyrosine kinase essential to tumor cell proliferation, differentiation and survival.
An orally bioavailable inhibitor of Janus-associated kinase 1 (JAK1) with potential antineoplastic activity. Upon oral administration of itacitinib, this agent selectively inhibits the phosphorylation and activity of JAK1, which may result in inhibition of JAK1-mediated signaling, induction of apoptosis, and reduction of cell proliferation in JAK1-expressing tumor cells. JAK1 is overexpressed in a variety of tumor cell types and plays a key role in tumor cell proliferation.
The mesylate salt form of enasidenib, an orally available inhibitor of specific mutant forms of the mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2), with potential antineoplastic activity. Upon administration, enasidenib specifically inhibits various mutant forms of IDH2, including the IDH2 variants R140Q, R172S, and R172K, which inhibits the formation of 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH2-expressing tumor cells. IDH2, an enzyme in the citric acid cycle, is mutated in a variety of cancers; it initiates and drives cancer growth by blocking differentiation and the production of the oncometabolite 2HG.
An orally available inhibitor of specific mutant forms of the mitochondrial enzyme isocitrate dehydrogenase type 2 (IDH2), with potential antineoplastic activity. Upon administration, enasidenib specifically inhibits various mutant forms of IDH2, including the IDH2 variants R140Q, R172S, and R172K, which inhibits the formation of 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH2-expressing tumor cells. IDH2, an enzyme in the citric acid cycle, is mutated in a variety of cancers; it initiates and drives cancer growth by blocking differentiation and the production of the oncometabolite 2HG.
The maleate salt form of neratinib, an orally available, quinazoline-based, irreversible inhibitor of both the receptor tyrosine kinases (RTKs) human epidermal growth factor receptor 2 (HER2; ERBB2) and human epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon administration, neratinib targets and covalently binds to the cysteine residue in the ATP-binding pockets of both HER2 and EGFR. This inhibits their activity and results in the inhibition of downstream signal transduction events, induces cell cycle arrest, apoptosis and ultimately decreases cellular proliferation in HER2- and EGFR-expressing tumor cells. EGFR and HER2, RTKs that are mutated or overactivated in many tumor cell types, play key roles in tumor cell proliferation and tumor vascularization.
A fully human, IgG2 monoclonal antibody directed against activin-like receptor kinase 1 (ALK-1) with potential antineoplastic activity. Ascrinvacumab binds to and neutralizes ALK-1. This may disrupt tumor endothelial cell function and inhibit tumor angiogenesis, eventually leading to an inhibition of tumor cell proliferation. ALK-1, a member of the transforming growth factor beta (TGF-b) type I receptor family, is overexpressed on endothelial cells in a variety of tumor cell types and increases endothelial cell proliferation and migration.
A humanized monoclonal antibody directed against the human alpha v integrin subunit with potential antiangiogenic and antineoplastic activities. Abituzumab, a chimeric antibody which includes the antigen binding sites of the anti-integrin mouse antibody 17E6, binds to and inhibits the activity of alphaVbeta3 integrin (vitronectin receptor); this may result in the inhibition of endothelial cell-cell interactions, endothelial cell-matrix interactions, and integrin-mediated tumor angiogenesis and metastasis in alphavbeta3-expressing tumor cells. AlphaVbeta3 integrin, a cell adhesion and signaling receptor, is expressed on the surface of tumor vessel endothelial cells and plays a crucial role in endothelial cell adhesion and migration.
A structural abnormality of the macula lutea, which is an oval-shaped highly pigmented yellow spot near the center of the retina. [HPO:probinson, PMID:16255686]
A plant whose flowers have been used in some cultures to treat certain medical problems. It is being studied in the relief of menopausal symptoms and may have anticancer effects.
Stage II includes: IIA: (T0, N1, M0); (T1, N1, M0); (T2, N0, M0) and IIB: (T2, N1, M0); (T3, N0, M0). T0: No evidence of primary tumor. T1: Tumor 2.0 cm or less in greatest dimension. T1 includes T1mi. T1mi: Tumor 1 mm or less in greatest dimension. T2: Tumor more than 2.0 cm but not more than 5.0 cm in greatest dimension. T3: Tumor more than 5.0 cm in greatest dimension. N1: Metastasis to movable ipsilateral axillary lymph node(s). M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage III includes: IIIA (T1, N1, M0); (T2, N1, M0); (T3, N1, M0); (T4, N0, M0); IIIB (T4, N1, M0); (Any T, N2, M0); (Any T, N3, M0). T1: Tumor 2 cm or less in greatest dimension. T2: tumor more than 2 cm but not more than 5 cm in greatest dimension. T3: Tumor more than 5 cm in greatest dimension. T4: Tumor of any size that invades adjacent organ(s). N1: Metastasis in perirectal lymph node(s). N2: Metastasis in unilateral internal iliac and/or inguinal lymph node(s). N3: Metastasis in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage I includes: (T1, N0, M0); (T2, N0, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IIIA includes: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0); (T4, N0, M0). T1: Tumor 2 cm or less in greatest dimension. T2: Tumor more than 2 cm but not more than 5 cm in greatest dimension. T3: Tumor more than 5 cm in greatest dimension. T4: Tumor of any size that invades adjacent organ(s). N1: Metastasis in perirectal lymph node(s). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage IIIB includes: (T4, N1, M0); (Any T, N2, M0); (Any T, N3, M0). T4: Tumor of any size that invades adjacent organ(s). N1: Metastasis in perirectal lymph node(s). N2: Metastasis in unilateral internal iliac and/or inguinal lymph node(s). N3: Metastasis in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
The reemergence of primary cutaneous T-cell non-Hodgkin lymphoma after a period of remission.
Stage I includes: T1, N0, M0. T1: Solitary tumor without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage II includes: T2, N0, M0. T2: Solitary tumor with vascular invasion or multiple tumors none more than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IV includes: IVA: (Any T, N1, M0); IVB: (Any T, Any N, M1). N1: Regional lymph node metastasis. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage II includes: IIA: (T2b, N0, M0); (T3a, N0, M0); IIB: (T3b, N0, M0); (T4a, N0, M0); IIC: (T4b, N0, M0). T2b: Cutaneous melanoma with a tumor measuring 1.01-2.0 mm in thickness, with ulceration. T3a: Cutaneous melanoma with a tumor measuring 2.01-4.0 mm in thickness, without ulceration. T3b: Cutaneous melanoma with a tumor measuring 2.01-4.0 mm in thickness, with ulceration. T4a: Cutaneous melanoma with a tumor measuring more than 4.0 mm in thickness, without ulceration. T4b: Cutaneous melanoma with a tumor measuring more than 4.0 mm in thickness, with ulceration. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 6th and 7th Eds.)
Stage IV includes: (Any T, Any N, M1). M1: Distant metastasis. (from AJCC 6th and 7th Eds.)
Stage II includes: IIA (T2a, N0, M0); IIB (T1, N1, M0), (T2, N1, M0), (T2a, N1, M0); (T2b, N0, M0); (T2b, N0, M0); (T2b, N1, M0). T2: Tumor extends to soft tissues. T2a: Tumor extends to the oropharynx and/or nasal cavity without parapharyngeal extension. T2b: Any tumor with parapharyngeal extension. N1: Unilateral metastasis in lymph node(s), 6 cm or less in greatest dimension, above the supraclavicular fossa. M0: No distant metastasis. (AJCC 6th ed.)
Stage I includes: T1, N0, M0. T1: Tumor measuring 2 cm or less in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage II includes: T2, N0, M0. T2: Tumor measuring more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor measuring more than 4 cm in greatest dimension, and/or tumor having extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. T1: Tumor measuring 2 cm or less in greatest dimension without extraparenchymal extension. T2: Tumor measuring more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB (T4b, Any N, M0); (Any T, N3, M0); IVC (Any T, Any N, M1). T4a: Moderately advanced disease. Tumor invades skin, mandible, ear canal, and/or facial nerve. T1: Tumor measuring 2 cm or less in greatest dimension without extraparenchymal extension. Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes. T2: Tumor measuring more than 2 cm, but not more than 4 cm in greatest dimension without extraparenchymal extension. T3: Tumor measuring more than 4 cm in greatest dimension, and/or tumor having extraparenchymal extension. T4b: Very advanced disease. Tumor invades skull base and/or pterygoid plates and/or encases carotid artery. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node, more than 6 cm in greatest dimension. M0: No distant metastasis. M1: Distant metastasis. (AJCC 7th ed.)
Stage IV includes: IVA (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB (Any T, N3, M0); (T4b, Any N, M0); IVC (Any T, Any N, M1). T4a (lip): Tumor invades through cortical bone, inferior alveolar nerve, floor of mouth, or skin of face, i.e., chin or nose. T4a (oral cavity): Tumor invades adjacent structures (e.g., through cortical bone, into deep [extrinsic] muscles of tongue, maxillary sinus, skin of face). T4b: Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N2a: Metastasis in a single ipsilateral lymph node more than 3 cm but not more than 6 cm in dimension. N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. N2c: Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M1: Distant metastasis. (AJCC 6th and 7th eds.)
Stage I includes: T1, N0, M0. T1: Tumor limited to one subsite of the hypopharynx and 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.)
Stage II includes: T2, N0, M0. T2: (Supraglottis) Tumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx. (Glottis) Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. (Subglottis) Tumor extends to vocal cord(s) with normal or impaired mobility. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T1: Supraglottis: Tumor limited to one subsite of supraglottis with normal vocal cord mobility. Glottis: Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility. Subglottis: Tumor limited to the subglottis. T2: Supraglottis: Tumor invades mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx. Glottis: Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. Subglottis: Tumor extends to vocal cord(s) with normal or impaired mobility. T3: Supraglottis: Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre-epiglottic tissues, paraglottic space, and/or inner cortex of thyroid cartilage. Glottis: Tumor limited to the larynx with vocal cord fixation and/or invasion of paraglottic space, and/or inner cortex of the thyroid cartilage. Subglottis: Tumor limited to larynx with vocal cord fixation. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3cm or less in greatest dimension. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage I includes: T1, N0, M0. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Nasal cavity and ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage II includes: T2, N0, M0. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Nasal cavity and ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Maxillary sinus: Tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. Nasal cavity and ethmoid sinus: Tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Nasal cavity and ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Nasal cavity and ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N2, M0). T3: Tumor more than 4 cm in greatest dimension. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension, or in multiple ipsilateral lymph nodes, none more than 6cm in greatest dimension, or in bilateral or contralateral lymph nodes, none more than 6cm in greatest dimension. M0: No distant metastasis. (AJCC 6th ed.)
Stage I includes: T1, N0, M0. T1: (Supraglottis) Tumor limited to one subsite of supraglottis with normal vocal cord mobility. (Glottis) Tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility. (Subglottis) Tumor limited to the subglottis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage 0 includes: Tis, N0, M0. Tis: Melanoma in situ. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 6th and 7th Eds.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage 0 includes: (Tis, N0, M0). Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage IVB includes: Any T, Any N, M1. M1: distant metastasis (including pelvic lymph node metastasis). (AJCC 6th and 7th eds.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ: intraepithelial or invasion of lamina propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Gastrin (101 aa, ~11 kDa) is encoded by the human GAST gene. This protein plays a role in the modulation of food digestion by the gastrointestinal system.
A second generation polyamine analogue, synthesized through the restriction of molecular conformations of parent polyamine compounds, with potential antineoplastic activity. Polyamine analogue PG11047 may displace endogenous polyamines from DNA binding sites, thereby interfering with cell cycle processes dependent upon polyamine binding and function, and resulting in cell-cycle arrest, induction of apoptosis, depletion of polyamines, and interference with gene and ligand-receptor activities involved with cell growth. This agent may exhibit decreased toxicity and enhanced cytotoxicity profiles compared to first-generation polyamine compounds. In tumor cells, there is an increase dependence on polyamines as well as a dysregulated polyamine metabolic pathway resulting in abnormal or sustained tumor growth.
A 25-mer antisense oligodeoxynucleotide phosphorothioate. GEM-91 is complementary to the gag mRNA of human immunodeficiency virus type 1 (HIV-1), resulting in HIV-1 replication inhibition. (NCI)
Stage 0 includes: For squamous cell carcinoma: Tis (HGD), N0, M0, G1, GX, Tumor location: Any. For adenocarcinoma: Tis (HGD), N0, M0, G1, GX. Tis: High-grade dysplasia. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well differentiated. GX: Grade cannot be assessed-stage grouping as G1. Tumor location: Location of the primary cancer site is defined by the position of the upper (proximal) edge of the tumor in the esophagus. (AJCC 7th ed.)
Cholecystokinin (115 aa, ~13 kDa) is encoded by the human CCK gene. This protein is involved in both pancreatic enzyme release and gallbladder contraction.
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ: intraepithelial or invasion of the lamina propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
A benign neoplasm characterized by the presence of connective tissue stroma and epithelial structures. It occurs in the ovary, fallopian tube, uterine corpus, and cervix. Cases of adenofibroma of the ovary with low grade malignant potential have also been reported.
Acute erythroid leukemia characterised by the presence of at least 50% erythroid precursors and at least 20% myeloblasts in the bone marrow. -- 2003
Acute erythroid leukemia characterised by the presence of immature erythroid cells in the bone marrow (at least 80% of the cellular component), without evidence of a significant myeloblastic cell population present. -- 2003
An abnormally decreased level of immunoglobulin IgG in blood. [HPO:probinson]
Stage II includes: II (T2, N0, M0); IIA (T2a, N0, M0); IIB (T2b, N0, M0). T2: Tumor invades cervix but does not extend beyond uterus. T2a: Tumor limited to the glandular epithelium of the endocervix. There is no evidence of connective tissue stromal invasion. T2b: Invasion of the stromal connective tissue of the cervix. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage III includes: III (T3, N0, M0); IIIA (T3a, N0, M0); IIIB (T3b, N0, M0); IIIC (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Local and/or regional spread as defined below. T3a: Tumor invades serosa and/or adnexa (direct extension or metastasis) and/or cancer cells in ascites or peritoneal washings. T3b Vaginal involvement (direct extension or metastasis). N0: No regional lymph node metastasis. N1: Regional lymph node metastasis to pelvic and/or para-aortic nodes. M0: No distant metastasis. (AJCC 6th ed.) - 2003
An intended site for a dose form that is for administration to the nose or nasal tissues.
Stage II includes: IIA: (T2b, N0, M0); (T3a, N0, M0); IIB: (T3b, N0, M0); (T4a, N0, M0); IIC: (T4b, N0, M0). T2b: Cutaneous melanoma with a tumor measuring 1.01-2.0 mm in thickness, with ulceration. T3a: Cutaneous melanoma with a tumor measuring 2.01-4.0 mm in thickness, without ulceration. T3b: Cutaneous melanoma with a tumor measuring 2.01-4.0 mm in thickness, with ulceration. T4a: Cutaneous melanoma with a tumor measuring more than 4.0 mm in thickness, without ulceration. T4b: Cutaneous melanoma with a tumor measuring more than 4.0 mm in thickness, with ulceration. N0: No regional lymph node metastases. M0: No detectable evidence of distant metastases. (from AJCC 6th and 7th Ed.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis. (AJCC 6th and 7th Eds.)
Stage I includes: I (T1, N0, M0); IA: (T1a, N0, M0); IB (T1b, N0, M0); IC (T1c, N0, M0). T1: Tumor confined to corpus uteri. T1a: Tumor limited to the endometrium. T1b: Tumor invades less than one-half of the myometrium. T1c: Tumor invades one-half or more of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.) - 2003
Stage IV includes: IVA: (T4, Any N, M0); IVB: (Any T, Any N, M1). T4: Tumor invades bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4). M1: Distant metastasis (includes metastasis to abdominal lymph nodes other than para-aortic, and/or inguinal lymph nodes: excludes metastasis to vagina, pelvic serosa, or adnexa). (AJCC 6th ed.) - 2003
Stage IV includes: IVA (T4, N0-1, M0); IVB (Any T, N2, M0); (Any T, Any N, M1). T4: Tumor invades the main portal vein or hepatic artery, or invades two or more extrahepatic organs or structures. N0: No regional lymph node metastasis. N1: Metastases to nodes along the cystic duct, common bile duct, hepatic artery, and/or portal vein. N2: Metastases to periaortic, pericaval, superior mesenteric artery, and/or celiac artery lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (from AJCC 7th Ed.)
Stage I includes: IA (T1, N0, M0); IB (T2, N0, M0). T1: Tumor limited to the pancreas 2 cm or less in greatest dimension. T2: Tumor limited to the pancreas, more than 2 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage II includes: IIA (T3, N0, M0); IIB (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T1: Tumor limited to the pancreas 2 cm or less in greatest dimension. T2: Tumor limited to the pancreas, more than 2 cm in greatest dimension. T3: Tumor extends beyond the pancreas but without involvement of the celiac axis or the superior mesenteric artery. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage III includes: T4, Any N, M0. T4: Tumor involves the celiac axis or the superior mesenteric artery. M0: No distant metastasis. (AJCC 6th and 7th Eds.)
Stage IV includes: IVA: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0); IVB (Any T, N3, M0); IVC (Any T, Any N, M1). T4: Tumor with intracranial extension and/or involvement of cranial nerves, infratemporal fossa, hypopharynx, orbit, or masticator space. N3: Metastasis in a lymph node(s). N3a: greater than 6 cm in dimension. N3b: extension to the supraclavicular fossa. M1: Distant metastasis. (AJCC 6th ed.)
Abnormality of the basal ganglia. [HPO:probinson]
Biliary atresia is a disorder of infants in which there is progressive obliteration or discontinuity of the extrahepatic biliary system, resulting in obstruction of bile flow. Untreated, the resulting cholestasis leads to progressive conjugated hyperbilirubinemia, cirrhosis, and hepatic failure (Bates et al., 1998). Most patients require liver transplantation within the first year of life (Leyva-Vega et al., 2010). See also Alagille syndrome (118450), which includes biliary atresia as a feature.
Stage IVB includes: (Any T, N3, M0); (T4b, Any N, M0). T4b: Lip cancer with very advanced local disease. Tumor invades masticator space, pterygoid plates, or skull base and/or encases internal carotid artery. N3: Metastasis in a lymph node more than 6 cm in greatest dimension. M0: No distant metastasis. (AJCC 7th ed.)
An intended site for a dose form that is for administration to the cervix uteri.
A syndrome characterized by the presence of three complete copies of genetic material for chromosome 21, instead of the normal two. It leads to a variety of abnormalities that include mental retardation, macroglossia, microgenia, epicanthic eyelids, and a single transverse palmar crease.
Stage IA includes: T1a, N0, M0. T1a: Tumor confined to the vulva and perineum, 2 cm or less in greatest dimension, and with stromal invasion no greater than 1 mm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IB includes: T1b, N0, M0. T1b: Vulvar cancer with tumor size greater than 2 cm, or any size with stromal invasion more than 1.0 mm, confined to the vulva or perineum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Body mass index percentile above the 85th and below the 95th percentile as compared to children of the same age and sex.
Acute lymphoblastic leukemia that does not respond to treatment.
A subjective score of 6 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
A form of the human glycoprotein antithrombin-III (AT-III), which is produced recombinantly or isolated from human plasma, with anticoagulant activity. Upon administration, antithrombin-III binds to and blocks thrombin activity, and prevents thrombus formation.
Problems traced to inadequate design or complete lack of safety measures leading to device malfunction or unintended properties of the device including possible hazards for persons using the device.
Safety measures are inadequately applied or missing.
An intended site for a dose form that is for administration to the urethra.
An intended site for a dose form that is for administration to the eye or eye structures.
An intended site for a dose form that is for administration to the skin in order to obtain an effect after absorption through the skin barrier.
An intended site for a dose form that is for administration to the vagina.
Granulocytes collected from a single donor and suspended in a specific volume of original plasma intended for patient infusion.
pH lower than expected and / or anticipated.
An increase in the diameter of the ring (annulus) of the mitral valve.
The fluid (noncellular) portion of the circulating blood, as distinguished from the serum that is the fluid portion of the blood.
A molecular abnormality characterized by rearrangement of a gene sequence that results in either aberrant gene expression or the translation of a novel protein.
A subjective score of 4 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
For hepatocellular carcinoma: Stage III includes: IIIA: (T3a, N0, M0); IIIB: (T3b, N0, M0); IIIC: (T4, N0, M0). T3a: Multiple tumors more than 5 cm. T3b: Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein. T4: Tumors(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. For intrahepatic cholangiocarcinoma: Stage III includes: T3, N0, M0. T3: Tumor perforating the visceral peritoneum or involving the local extra hepatic structures by direct invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 7th Ed.)
For hepatocellular carcinoma: Stage IIIC includes: T4, N0, M0. T4: Tumors(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
A localized non-invasive adenocarcinoma of the lung measuring 3 cm or less. It is characterized by a pure lepidic growth pattern and the lack of stromal, vascular, or pleural invasion.
A subjective score of 0 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
A subjective score of 1 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
Stage I includes: IA: (T1, N0, M0); IB: (T2 or T3, N0, M0). T1: Tumor limited to the ipsilateral parietal with or without involvement of visceral pleura, mediastinal pleura, and diaphragmatic pleura. T2: Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of diaphragmatic muscle and/or extension of tumor from visceral pleura into the underlying pulmonary parenchyma. T3: Tumor is locally advanced but potentially resectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of the endothoracic fascia, extension into the mediastinal fat, solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall, and/or nontransmural involvement of the pericardium. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage IB includes: T2 or T3, N0, M0. T2: Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of diaphragmatic muscle and/or extension of tumor from visceral pleura into the underlying pulmonary parenchyma. T3: Tumor is locally advanced but potentially resectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of the endothoracic fascia, extension into the mediastinal fat, solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall, and/or nontransmural involvement of the pericardium. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T1, N1, M0); (T2, N1, M0). T1: Tumor limited to the ipsilateral parietal with or without involvement of visceral pleura, mediastinal pleura, and diaphragmatic pleura. T2: Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of diaphragmatic muscle and/or extension of tumor from visceral pleura into the underlying pulmonary parenchyma. N1: Metastases in the ipsilateral bronchopulmonary, hilar, or mediastinal (including the internal mammary, peridiaphragmatic, pericardial fat pad, or intercostal) lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T3, N1, M0); IIIB: (T1-3, N2, M0); (T4, Any N, M0). T1: Tumor limited to the ipsilateral parietal with or without involvement of visceral pleura, mediastinal pleura, and diaphragmatic pleura. T2: Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of diaphragmatic muscle and/or extension of tumor from visceral pleura into the underlying pulmonary parenchyma. T3: Tumor is locally advanced but potentially resectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of the endothoracic fascia, extension into the mediastinal fat, solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall, and/or nontransmural involvement of the pericardium. T4: Tumor is locally advanced and technically unresectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction, direct transdiaphragmatic extension of tumor to the peritoneum, direct extension of tumor to the contralateral pleura, direct extension of tumor to mediastinal organs, direct extension of tumor into the spine, and/or tumor extending through to the internal surface of the pericardium with or without a pericardial effusion; or tumor involving the myocardium. N1: Metastases in the ipsilateral bronchopulmonary, hilar, or mediastinal (including the internal mammary, peridiaphragmatic, pericardial fat pad, or intercostal) lymph nodes. N2: Metastases in the contralateral mediastinal, ipsilateral, or contralateral supraclavicular lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis present. (AJCC 8th ed.)
Stage IA includes: T1, N0, M0. T1: Tumor limited to the ipsilateral parietal with or without involvement of visceral pleura, mediastinal pleura, and diaphragmatic pleura. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: IA: (T1, N0, M0, G1 or GX); IB: (T2, N0, M0, G1 or GX); (T3, N0, M0, G1 or GX). T1: Tumor measuring 8 cm or less in greatest dimension. T2: Tumor measuring more than 8 cm in greatest dimension. T3: Discontinuous tumors in the primary bone site. N0: No regional lymph node metastasis. M0: No distant metastasis. GX: Grade cannot be assessed. G1: Well differentiated, low grade. (AJCC 8th ed.)
Stage IA includes: T1, N0, M0, G1 or GX. T1: Tumor measuring 8 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. GX: Grade cannot be assessed. G1: Well differentiated, low grade. (AJCC 8th ed.)
Stage IB includes: (T2, N0, M0, G1 or GX); (T3, N0, M0, G1 or GX). T2: Tumor measuring more than 8 cm in greatest dimension. T3: Discontinuous tumors in the primary bone site. N0: No regional lymph node metastasis. M0: No distant metastasis. GX: Grade cannot be assessed. G1: Well differentiated, low grade. (AJCC 8th ed.)
Stage II includes: IIA: (T1, N0, M0, G2 or G3); IIB: (T2, N0, M0, G2 or G3). T1: Tumor measuring 8 cm or less in greatest dimension. T2: Tumor measuring more than 8 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G2: Moderately differentiated, high grade. G3: Poorly differentiated, high grade. (AJCC 8th ed.)
Stage IIA includes: T1, N0, M0, G2 or G3. T1: Tumor measuring 8 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G2: Moderately differentiated, high grade. G3: Poorly differentiated, high grade. (AJCC 8th ed.)
Stage IIB includes: T2, N0, M0, G2 or G3. T2: Tumor measuring more than 8 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. G2: Moderately differentiated, high grade. G3: Poorly differentiated, high grade. (AJCC 8th ed.)
Stage III includes: T3, N0, M0, G2 or G3. T3: Discontinuous tumors in the primary bone site. N0: No regional lymph node metastasis. M0: No distant metastasis. G2: Moderately differentiated, high grade. G3: Poorly differentiated, high grade. (AJCC 8th ed.)
Stage IV includes: IVA: (Any T, N0, M1a, Any G); IVB: (Any T, N1, Any M, Any G); (Any T, Any N, M1b, Any G). N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M1a: Metastasis in the lung. M1b: Metastasis in the bone or other distant sites. (AJCC 8th ed.)
Stage IVA includes: Any T, N0, M1a, Any G. N0: No regional lymph node metastasis. M1a: Metastasis in the lung. (AJCC 8th ed.)
Stage IVB includes: (Any T, N1, Any M, Any G); (Any T, Any N, M1b, Any G). N1: Regional lymph node metastasis. M1b: Metastasis in the bone or other distant sites. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Nasal cavity and ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Nasal cavity and ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Maxillary sinus: Tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. Nasal cavity and ethmoid sinus: Tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Nasal cavity and ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Nasal cavity and ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (T4b, Any N, M0); (Any T, N3, M0); IVC: (Any T, Any N, M1). T4a: Maxillary sinus: Moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. Nasal cavity and ethmoid sinus: Moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. T4b: Very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx, or clivus. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Nasal cavity and ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Nasal cavity and ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. T3: Maxillary sinus: Tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. Nasal cavity and ethmoid sinus: Tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). N2: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes , none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). N3: Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral or bilateral nodes, any with ENE(+). M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Maxillary sinus: Moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. Nasal cavity and ethmoid sinus: Moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. T1: Maxillary sinus: Tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. Nasal cavity and ethmoid sinus: Tumor restricted to any one subsite, with or without bony invasion. T2: Maxillary sinus: Tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. Nasal cavity and ethmoid sinus: Tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. T3: Maxillary sinus: Tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. Nasal cavity and ethmoid sinus: Tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). N2: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes , none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: (T4b, Any N, M0); (Any T, N3, M0). T4b: Very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx, or clivus. N3: Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral or bilateral nodes, any with ENE(+). M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Supraglottis: Tumor is limited to one subsite of supraglottis with normal vocal cord mobility. Glottis: Tumor is limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility. Subglottis: Tumor is limited to the subglottis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Supraglottis: Tumor invades the mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of the tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx. Glottis: Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. Subglottis: Tumor extends to vocal cord(s) with normal or impaired mobility. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Supraglottis: Tumor is limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage. Glottis: Tumor is limited to the larynx with vocal cord fixation and /or invades the paraglottic space, and/or inner cortex of the thyroid cartilage. Subglottis: Tumor is limited to the larynx with vocal cord fixation and/or invades the paraglottic space and/or inner cortex of the thyroid cartilage. T1: Supraglottis: Tumor is limited to one subsite of supraglottis with normal vocal cord mobility. Glottis: Tumor is limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility. Subglottis: Tumor is limited to the subglottis. T2: Supraglottis: Tumor invades the mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of the tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx. Glottis: Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. Subglottis: Tumor extends to vocal cord(s) with normal or impaired mobility. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0); IVB: (Any T, N3, M0); (T4b, Any N, M0); IVC: (Any T, Any N, M1). T4a: Supraglottis: Moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). Glottis: Moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, cricoid cartilage, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). Subglottis: Moderately advanced local disease. Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). T3: Supraglottis: Tumor is limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage. Glottis: Tumor is limited to the larynx with vocal cord fixation and /or invades the paraglottic space, and/or inner cortex of the thyroid cartilage. Subglottis: Tumor is limited to the larynx with vocal cord fixation and/or invades the paraglottic space and/or inner cortex of the thyroid cartilage. T1: Supraglottis: Tumor is limited to one subsite of supraglottis with normal vocal cord mobility. Glottis: Tumor is limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility. Subglottis: Tumor is limited to the subglottis. T2: Supraglottis: Tumor invades the mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of the tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx. Glottis: Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. Subglottis: Tumor extends to vocal cord(s) with normal or impaired mobility. T4b: Supraglottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. Glottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. Subglottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). N2: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-); or metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). N3: metastasis in a lymph node, more than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node, more than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes and any with ENE(+). M0: No distant metastasis. M1: distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4a, N0, M0); (T4a, N1, M0); (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4a, N2, M0). T4a: Supraglottis: Moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). Glottis: Moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, cricoid cartilage, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). Subglottis: Moderately advanced local disease. Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). T3: Supraglottis: Tumor is limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage. Glottis: Tumor is limited to the larynx with vocal cord fixation and /or invades the paraglottic space, and/or inner cortex of the thyroid cartilage. Subglottis: Tumor is limited to the larynx with vocal cord fixation and/or invades the paraglottic space and/or inner cortex of the thyroid cartilage. T1: Supraglottis: Tumor is limited to one subsite of supraglottis with normal vocal cord mobility. Glottis: Tumor is limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility. Subglottis: Tumor is limited to the subglottis. T2: Supraglottis: Tumor invades the mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of the tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx. Glottis: Tumor extends to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. Subglottis: Tumor extends to vocal cord(s) with normal or impaired mobility. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). N2: Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-); or metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: (Any T, N3, M0); (T4b, Any N, M0). T4b: Supraglottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. Glottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. Subglottis: Very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. N3: metastasis in a lymph node, more than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node, more than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes and any with ENE(+). M0: No distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0. Tis: High-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: T1, N1, M0; IIB: T2, N0, M0. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T1, N1, M0. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T2, N0, M0. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T2, N1, M0); (T3, N0-1, M0); (T4a, N0-1, M0). T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T1-4a, N2, M0); (T4b, N0-2, M0); (Any T, N3, M0); IVB: (Any T, Any N, M1). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. T4b: Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T1-4a, N2, M0); (T4b, N0-2, M0); (Any T, N3, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. T4b: Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0, GN/A. Tis: High-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane. N0: No regional lymph node metastasis. M0: No distant metastasis. GN/A: Grade non-applicable. (AJCC 8th ed.)
Stage I includes: IA: (T1a, N0, M0, G1); (T1a, N0, M0, GX); IB: (T1a, N0, M0, G2); (T1b, N0, M0, G1-2); (T1b, N0, M0, GX); IC: (T1, N0, M0, G3); (T2, N0, M0, G1-2). T1a: Tumor invades the lamina propria or muscularis mucosae. T1b: Tumor invades the submucosa. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well-differentiated. GX: Grade cannot be assessed. G2: Moderately differentiated. G3: Poorly differentiated, undifferentiated. (AJCC 8th ed.)
Stage IA includes: (T1a, N0, M0, G1); (T1a, N0, M0, GX). T1a: Tumor invades the lamina propria or muscularis mucosae. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well-differentiated. GX: Grade cannot be assessed. (AJCC 8th ed.)
Stage IB includes: (T1a, N0, M0, G2); (T1b, N0, M0, G1-2); (T1b, N0, M0, GX). T1a: Tumor invades the lamina propria or muscularis mucosae. T1b: Tumor invades the submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well-differentiated. GX: Grade cannot be assessed. G2: Moderately differentiated. (AJCC 8th ed.)
Stage II includes: IIA: (T2, N0, M0, G3); (T2, N0, M0, GX); IIB: (T1, N1, M0, Any G); (T3, N0, M0, Any G). T2: Tumor invades the muscularis propria. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. GX: Grade cannot be assessed. G3: Poorly differentiated, undifferentiated. (AJCC 8th ed.)
Stage IIA includes: (T2, N0, M0, G3); (T2, N0, M0, GX). T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. GX: Grade cannot be assessed. G3: Poorly differentiated, undifferentiated. (AJCC 8th ed.)
Stage IIB includes: (T1, N1, M0, Any G); (T3, N0, M0, Any G). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T1, N2, M0, Any G); (T2, N1, M0, Any G); IIIB: (T2, N2, M0, Any G); (T3, N1-2, M0, Any G); (T4a, N0-1, M0, Any G). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
ANOA is an autosomal recessive neurologic disorder characterized by onset of visual and hearing impairment in the first or second decades (summary by Paul et al., 2017).
DFNA34 is an autosomal dominant form of postlingual, slowly progressive sensorineural hearing loss with variable severity and variable additional features. Some patients have pure hearing loss without significant additional features, whereas some patients have features of an autoinflammatory disorder with systemic manifestations, including periodic fevers, arthralgias, and episodic urticaria. The disorder results from abnormally increased activation of the inflammatory pathway, and treatment with an IL1 receptor antagonist (see 147679) may be effective if started early (summary by Nakanishi et al., 2017).
Stage IIIA includes: (T1, N2, M0, Any G); (T2, N1, M0, Any G). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T2, N2, M0, Any G); (T3, N1-2, M0, Any G); (T4a, N0-1, M0, Any G). T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T4a, N2, M0, Any G); (T4b, N0-2, M0, Any G); (Any T, N3, M0, Any G); IVB: (Any T, Any N, M1, Any G). T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. T4b: Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4a, N2, M0, Any G); (T4b, N0-2, M0, Any G); (Any T, N3, M0, Any G). T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. T4b: Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: Any T, Any N, M1, Any G. M1: Distant metastasis. (AJCC 8th ed.)
Stage I includes: T0-2, N0, M0. T0: No evidence of primary tumor. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T3, N0, M0. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T0-2, N1, M0); IIIB: (T3, N1, M0); (T0-3, N2, M0); (T4a, N0, M0). T0: No evidence of primary tumor. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: T0-2, N1, M0. T0: No evidence of primary tumor. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T3, N1, M0); (T0-3, N2, M0); (T4a, N0, M0). T0: No evidence of primary tumor. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T4a, N1-2, M0); (T4a, NX, M0); (T4b, N0-2, M0); (Any T, N3, M0); IVB: (Any T, Any N, M1). T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. T4b: Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway. NX: Regional lymph nodes cannot be assessed. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4a, N1-2, M0); (T4a, NX, M0); (T4b, N0-2, M0); (Any T, N3, M0). T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. T4b: Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway. NX: Regional lymph nodes cannot be assessed. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0-1, M0. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T2, N0-1, M0); (T3, N0, M0). T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N1, M0); (T1-3, N2, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T4, N0-2, M0); (Any T, N3, M0); IVB: (Any T, Any N, M1). T4: Tumor invades adjacent structures. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4, N0-2, M0); (Any T, N3, M0). T4: Tumor invades adjacent structures. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0, GN/A, Tumor location: Any. Tis: High-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane. N0: No regional lymph node metastasis. M0: No distant metastasis. GN/A: Grade non-applicable. (AJCC 8th ed.)
Stage I includes: IA: (T1a, N0, M0, G1, Tumor location: Any); (T1a, N0, M0, GX, Tumor location: Any); IB: (T1a, N0, M0, G2-3, Tumor location: Any); (T1b, N0, M0, G1-3, Tumor location: Any); (T1b, N0, M0, GX, Tumor location: Any); (T2, N0, M0, G1, Tumor location: Any). T1a: Tumor invades the lamina propria or muscularis mucosae. T1b: Tumor invades the submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well-differentiated. GX: Grade cannot be assessed. G2: Moderately differentiated. G3: Poorly differentiated, undifferentiated. (AJCC 8th ed.)
Stage IA includes: (T1a, N0, M0, G1, Tumor location: Any); (T1a, N0, M0, GX, Tumor location: Any). T1a: Tumor invades the lamina propria or muscularis mucosae. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well-differentiated. GX: Grade cannot be assessed. (AJCC 8th ed.)
Stage IB includes: (T1a, N0, M0, G2-3, Tumor location: Any); (T1b, N0, M0, G1-3, Tumor location: Any); (T1b, N0, M0, GX, Tumor location: Any); (T2, N0, M0, G1, Tumor location: Any). T1a: Tumor invades the lamina propria or muscularis mucosae. T1b: Tumor invades the submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well-differentiated. GX: Grade cannot be assessed. G2: Moderately differentiated. G3: Poorly differentiated, undifferentiated. (AJCC 8th ed.)
Stage II includes: IIA: (T2, N0, M0, G2-3, Tumor location: Any); (T2, N0, M0, GX, Tumor location: Any); (T3, N0, M0, Any G, Tumor location: Lower); (T3, N0, M0, G1, Tumor location: Upper/middle); IIB: (T3, N0, M0, G2-3, Tumor location: Upper/middle); (T3, N0, M0, GX, Tumor location: Any); (T3, N0, M0, Any G, Tumor location: Unknown); (T1, N1, M0, Any G, Tumor location: Any). T2: Tumor invades the muscularis propria. T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. GX: Grade cannot be assessed. G1: Well-differentiated. G2: Moderately differentiated. G3: Poorly differentiated, undifferentiated. (AJCC 8th ed.)
Stage IIA includes: (T2, N0, M0, G2-3, Tumor location: Any); (T2, N0, M0, GX, Tumor location: Any); (T3, N0, M0, Any G, Tumor location: Lower); (T3, N0, M0, G1, Tumor location: Upper/middle). T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. M0: No distant metastasis. GX: Grade cannot be assessed. G1: Well-differentiated. G2: Moderately differentiated. G3: Poorly differentiated, undifferentiated. (AJCC 8th ed.)
Stage IIB includes: (T3, N0, M0, G2-3, Tumor location: Upper/middle); (T3, N0, M0, GX, Tumor location: Any); (T3, N0, M0, Any G, Tumor location: Unknown); (T1, N1, M0, Any G, Tumor location: Any). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T3: Tumor invades adventitia. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. GX: Grade cannot be assessed. G2: Moderately differentiated. G3: Poorly differentiated, undifferentiated (AJCC 8th ed.)
Stage III includes: IIIA: (T1, N2, M0, Any G, Tumor location: Any); (T2, N1, M0, Any G, Tumor location: Any); IIIB: (T2, N2, M0, Any G, Tumor location: Any); (T3, N1-2, M0, Any G, Tumor location: Any); (T4a, N0-1, M0, Any G, Tumor location: Any). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: (T1, N2, M0, Any G, Tumor location: Any); (T2, N1, M0, Any G, Tumor location: Any). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T2, N2, M0, Any G, Tumor location: Any); (T3, N1-2, M0, Any G, Tumor location: Any); (T4a, N0-1, M0, Any G, Tumor location: Any). T2: Tumor invades the muscularis propria. T3: Tumor invades adventitia. T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T4a, N2, M0, Any G, Tumor location: Any); (T4b, N0-2, M0, Any G, Tumor location: Any); (Any T, N3, M0, Any G, Tumor location: Any); IVB: (Any T, Any N, M1, Any G, Tumor location: Any). T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. T4b: Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4a, N2, M0, Any G, Tumor location: Any); (T4b, N0-2, M0, Any G, Tumor location: Any); (Any T, N3, M0, Any G, Tumor location: Any). T4a: Tumor invades the pleura, pericardium, azygos vein, diaphragm, or peritoneum. T4b: Tumor invades other adjacent structures, such as the aorta, vertebral body, or airway. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: Any T, Any N, M1, Any G, Tumor location: Any. M1: Distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ: intraepithelial tumor without invasion of the lamina propria, high grade dysplasia. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: (T1, N0, M0); (T2, N0, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: (T1, N1, N2, or N3, M0); (T2, N1, N2, or N3, M0); IIB: (T3, N0, M0); (T4a, N0, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N1, N2, or N3, M0); (T4a, N1, N2, or N3, M0). T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (T4b, Any N, M0); IVB: (Any T, Any N, M1). T4b: Tumor invades adjacent structures/organs. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
An intended site for a dose form that is for administration into the stomach or duodenum by means of an appropriate device.
Stage I includes: IA: (T1, N0, M0); IB: (T1, N1, M0); (T2, N0, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA includes: (T1, N0, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IB includes: (T1, N1, M0); (T2, N0, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: (T1, N2, M0); (T2, N1, M0); (T3, N0, M0); IIB: (T1, N3a, M0); (T2, N2, M0); (T3, N1, M0); (T4a, N0, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3a: Tumor with metastasis in seven to fifteen regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: (T1, N2, M0); (T2, N1, M0); (T3, N0, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: (T1, N3a, M0); (T2, N2, M0); (T3, N1, M0); (T4a, N0, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3a: Tumor with metastasis in seven to fifteen regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T2, N3a, M0); (T3, N2, M0); (T4a, N1, M0); (T4a, N2, M0); (T4b, N0, M0); IIIB: (T1, N3b, M0); (T2, N3b, M0); (T3, N3a, M0); (T4a, N3a, M0); (T4b, N1, M0); (T4b, N2, M0); IIIC: (T3, N3b, M0); (T4a, N3b, M0); (T4b, N3a, M0); (T4b, N3b, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). T4b: Tumor invades adjacent structures/organs. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3a: Tumor with metastasis in seven to fifteen regional lymph nodes. N3b: Tumor with metastasis in sixteen or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: (T2, N3a, M0); (T3, N2, M0); (T4a, N1, M0); (T4a, N2, M0); (T4b, N0, M0). T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). T4b: Tumor invades adjacent structures/organs. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3a: Tumor with metastasis in seven to fifteen regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T1, N3b, M0); (T2, N3b, M0); (T3, N3a, M0); (T4a, N3a, M0); (T4b, N1, M0); (T4b, N2, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). T4b: Tumor invades adjacent structures/organs. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3a: Tumor with metastasis in seven to fifteen regional lymph nodes. N3b: Tumor with metastasis in sixteen or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIC includes: (T3, N3b, M0); (T4a, N3b, M0); (T4b, N3a, M0); (T4b, N3b, M0). T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). T4b: Tumor invades adjacent structures/organs. N3a: Tumor with metastasis in seven to fifteen regional lymph nodes. N3b: Tumor with metastasis in sixteen or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: Any T, Any N. M1: Distant metastasis. (AJCC 8th ed.)
Stage I includes: (T1, N0, M0); (T2, N0, M0); (T1, N1, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T3, N0, M0); (T2, N1, M0); (T1, N2, M0); (T4a, N0, M0); (T3, N1, M0); (T2, N2, M0); (T1, N3, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T4a, N1, M0); (T3, N2, M0); (T2, N3, M0); (T4b, N0, M0); (T4b, N1, M0); (T4a, N2, M0); (T3, N3, M0); (T4b, N2, M0); (T4b, N3, M0); (T4a, N3, M0). T2: Tumor invades the muscularis propria. T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). T4b: Tumor invades adjacent structures/organs. N0: No regional lymph node metastasis. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: (T1, N1, N2, or N3, M0); (T2, N1, N2, or N3, M0). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N1: Tumor with metastasis in one or two regional lymph nodes. N2: Tumor with metastasis in three to six regional lymph nodes. N3: Tumor with metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: (T3, N0, M0); (T4a, N0, M0). T3: Tumor penetrates the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. T4a: Tumor invades the serosa (visceral peritoneum). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0. Tis: High-grade squamous intraepithelial lesion (previously termed carcinoma in situ, Bowen disease, anal intraepithelial neoplasia II-III, high-grade anal intraepithelial neoplasia). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor 2 cm or smaller. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: T2, N0, M0; IIB: T3, N0, M0. T2: Tumor larger than 2 cm but equal to or smaller than 5 cm. T3: Tumor larger than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T1, N1, M0); (T2, N1, M0); IIIB: (T4, N0, M0); IIIC: (T3, N1, M0); (T4, N1, M0). T1: Tumor 2 cm or smaller. T2: Tumor larger than 2 cm but equal to or smaller than 5 cm. T3: Tumor larger than 5 cm. T4: Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder. N0: No regional lymph node metastasis. N1: Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: (T1, N1, M0); (T2, N1, M0). T1: Tumor 2 cm or smaller. T2: Tumor larger than 2 cm but equal to or smaller than 5 cm. N1: Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: T4, N0, M0. T4: Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ (intramucosal carcinoma; invasion of the lamina propria or extension into but not through the muscularis mucosae). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: (T1, N0, M0); (T2, N0, M0). T1: Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria). T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor invades through the muscularis propria into the subserosa or the mesoappendix. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T4a, N0, M0. T4a: Tumor invades through the visceral peritoneum, including the acellular mucin or mucinous epithelium involving the serosa of the appendix or serosa of the mesoappendix. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIC includes: T4b, N0, M0. T4b: Tumor directly invades or adheres to adjacent organs or structures. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: (T1, N1, M0); (T2, N1, M0). T1: Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria). T2: Tumor invades the muscularis propria. N1: One to three regional lymph nodes are positive (tumor in lymph node measuring 0.2 mm or more) or any number of tumor deposits is present, and all identifiable lymph nodes are negative. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T3, N1, M0); (T4, N1, M0). T3: Tumor invades through the muscularis propria into the subserosa or the mesoappendix. T4: Tumor invades the visceral peritoneum, including the acellular mucin or mucinous epithelium involving the serosa of the appendix or mesoappendix, and/or directly invades adjacent organs or structures. N1: One to three regional lymph nodes are positive (tumor in lymph node measuring 0.2 mm or more) or any number of tumor deposits is present, and all identifiable lymph nodes are negative. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIC includes: Any T, N2, M0. N2: Four or more regional lymph nodes are positive. M0: No distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (Any T, N0, M1a); (Any T, Any N, M1b, G1). N0: No regional lymph node metastasis. M1a: Intraperitoneal acellular mucin, without identifiable tumor cells in the disseminated peritoneal mucinous deposits. M1b: Intraperitoneal metastasis only, including peritoneal mucinous deposits containing tumor cells. G1: Well differentiated. (AJCC 8th ed.)
Stage IVB includes: Any T, Any N, M1b, G2, G3, or GX. M1b: Intraperitoneal metastasis only, including peritoneal mucinous deposits containing tumor cells. G2: Moderately differentiated. G3: Poorly differentiated. GX: Grade cannot be assessed. (AJCC 8th ed.)
Stage IVC includes: Any T, Any N, M1c, Any G. M1c: Metastasis to sites other than peritoneum. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ/high grade dysplasia. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor confined to the bile duct, with extension up to the muscle layer or fibrous tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2a-b, N0, M0. T2a: Tumor invading beyond the wall of the bile duct to surrounding adipose tissue. T2b: Tumor invading adjacent hepatic parenchyma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: T3, N0, M0. T3: Tumor invading unilateral branches of the portal vein or hepatic artery. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: T4, N0, M0. T4: Tumor invading the main portal vein or its branches bilaterally, or the common hepatic artery; or unilateral second-order biliary radicals with contralateral portal vein or hepatic artery involvement. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IVA includes: Any T, N2, M0. N2: Four or more positive lymph nodes involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ/high-grade dysplasia. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: (T1, N1, M0); (T2, N0, M0). T1: Tumor invading the bile duct wall with a depth less than 5 mm. T2: Tumor invading the bile duct wall with a depth of 5-12 mm. N0: No regional lymph node metastasis. N1: Metastasis in one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: (T2, N1, M0); (T3, N0, M0); (T3, N1, M0). T2: Tumor invading the bile duct wall with a depth of 5-12 mm. T3: Tumor invading the bile duct wall with a depth greater than 12 mm. N0: No regional lymph node metastasis. N1: Metastasis in one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); IIIB: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0). T1: Tumor invading the bile duct wall with a depth less than 5 mm. T2: Tumor invading the bile duct wall with a depth of 5-12 mm. T3: Tumor invading the bile duct wall with a depth greater than 12 mm. T4: Tumor involving the celiac axis, superior mesenteric artery, and/or common hepatic artery. N0: No regional lymph node metastasis. N1: Metastasis in one to three regional lymph nodes. N2: Metastasis in four or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
An intended site for a dose form that is for administration to the gingivae.
Stage I includes: IA: (T1a, N0, M0); IB: (T1b, N0, M0); (T2, N0, M0). T1a: Tumor limited to ampulla of Vater or sphincter of Oddi. T1b: Tumor invading beyond the sphincter of Oddi (perisphincteric invasion) and/or into the duodenal submucosa. T2: Tumor invading into the muscularis propria of the duodenum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA includes: T1a, N0, M0. T1a: Tumor limited to ampulla of Vater or sphincter of Oddi. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IB includes: (T1b, N0, M0); (T2, N0, M0). T1b: Tumor invading beyond the sphincter of Oddi (perisphincteric invasion) and/or into the duodenal submucosa. T2: Tumor invading into the muscularis propria of the duodenum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: T3a, N0, M0; IIB: T3b, N0, M0. T3a: Tumor directly invading the pancreas (up to 0.5 cm). T3b: Tumor extending more than 0.5 cm into the pancreas, or extending into peripancreatic tissue or duodenal serosa without involvement of the celiac axis or superior mesenteric artery. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T3a, N0, M0. T3a: Tumor directly invading the pancreas (up to 0.5 cm). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T3b, N0, M0. T3b: Tumor extending more than 0.5 cm into the pancreas, or extending into peripancreatic tissue or duodenal serosa without involvement of the celiac axis or superior mesenteric artery. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T1a, N1, M0); (T1b, N1, M0); (T2, N1, M0); (T3a, N1, M0); (T3b, N1, M0); IIIB: (T4, Any N, M0); (Any T, N2, M0). T1a: Tumor limited to ampulla of Vater or sphincter of Oddi. T1b: Tumor invading beyond the sphincter of Oddi (perisphincteric invasion) and/or into the duodenal submucosa. T2: Tumor invading into the muscularis propria of the duodenum. T3a: Tumor directly invading the pancreas (up to 0.5 cm). T3b: Tumor extending more than 0.5 cm into the pancreas, or extending into peripancreatic tissue or duodenal serosa without involvement of the celiac axis or superior mesenteric artery. T4: Tumor involving the celiac axis, superior mesenteric artery, and/or common hepatic artery, irrespective of size. N1: Metastasis to one to three regional lymph nodes. N2: Metastasis to four or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. This includes high-grade pancreatic intraepithelial neoplasia (PanIn-3), intraductal papillary mucinous neoplasm with high-grade dysplasia, intraductal tubulopapillary neoplasm with high-grade dysplasia, and mucinous cystic neoplasm with high-grade dysplasia. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: IA: (T1, N0, M0); IB: (T2, N0, M0). T1: Tumor measuring 2 cm or less in greatest dimension. T2: Tumor measuring more than 2 cm and 4 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA includes: T1, N0, M0. T1: Tumor measuring 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IB includes: T2, N0, M0. T2: Tumor measuring more than 2 cm and 4 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: (T3, N0, M0); IIB: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T1: Tumor measuring 2 cm or less in greatest dimension. T2: Tumor measuring more than 2 cm and 4 cm or less in greatest dimension. T3: Tumor measuring more than 4 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Metastasis in one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor measuring more than 4 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T1: Tumor measuring 2 cm or less in greatest dimension. T2: Tumor measuring more than 2 cm and 4 cm or less in greatest dimension. T3: Tumor measuring more than 4 cm in greatest dimension. N1: Metastasis in one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (T4, Any N, M0). T1: Tumor measuring 2 cm or less in greatest dimension. T2: Tumor measuring more than 2 cm and 4 cm or less in greatest dimension. T3: Tumor measuring more than 4 cm in greatest dimension. T4: Tumor involving the celiac axis, superior mesenteric artery, and/or common hepatic artery, regardless of size. N2: Metastasis in four or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA includes: T1a, N0, M0. T1a: Pleural mesothelioma with no involvement of the visceral pleura. N0: No regional lymph metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IB includes: T1b, N0, M0. T1b: Pleural mesothelioma with a tumor also involving the visceral pleura N0: No regional lymph metastasis. M0: No distant metastasis. (AJCC 7th ed.)
An intended site for a dose form that is for administration to the rectum.
Stage III includes: IIIA (T1-T2, N1/N1c, M0); (T1, N2a, M0); IIIB (T3-T4a, N1/N1c, M0); (T2-T3, N2a, M0); (T1-T2, N2b, M0); IIIC (T4a, N2a, M0); (T3-T4a, N2b, M0); (T4b, N1-N2, M0). T1: Tumor invades submucosa. T2: Tumor invades muscularis propria. T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor penetrates to the surface of the visceral peritoneum. T4b: Tumor directly invades or is adherent to other organs or structures. N1: Metastasis in 1-3 regional lymph nodes. N1c: Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional lymph node metastasis. N2: Metastasis in four or more regional lymph nodes. N2a: Metastasis in 4-6 regional lymph nodes. N2b: Metastasis in seven or more regional lymph nodes. M0: No distant metastasis. (AJCC 7th ed.)
An intended site for a dose form that is for administration to the external ear or ear canal.
An intended site for a dose form that is for administration by swallowing.
An intended site for a dose form that is for administration to the oral cavity.
A response indicating than an individual is or was better than others.
A subjective score of 5 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
A finding indicating that a cellular sample has high microsatellite instability and/or a functional loss of a protein involved in the DNA mismatch repair process.
Problem with the device associated with the violent bursting due to the sudden expansion of air, gas or fluid.
An orally bioavailable dietary supplement composed of an extract from grape seeds containing high amounts of polyphenols, particularly lower proanthocyanidin oligomers (OPCs) and catechins, with antioxidant and chemopreventive activities. Upon administration, the active components in the grape seed extract (GSE) scavenge free radicals, protect against oxidation of low-density lipoprotein (LDL), and inhibit cell damage due to reactive oxygen species (ROS). This inhibits oxidative stress and protects against DNA damage. GSE also inhibits enzymes involved in inflammation, cell replication and DNA synthesis, and induces the expression of anti-oxidant enzymes. This may inhibit growth and induce apoptosis of cancer cells.
Problem with all or part of an implanted or invasive device moving from its intended location within the body.
A preparation containing antihemophilic factor obtained from a single unit of plasma.
Donations from a donor who presents to the collecting facility at the request of another person intending to provide products to be used by that person during some future therapeutic procedure.
Reproductive Human Cells, Tissues and Tissue based Products (HCT/Ps) donated by a donor to a specific recipient who knows and is known by the recipient before donation.
An invasive adenocarcinoma that arises from the lung. It is characterized by the presence of tall columnar cells and mucin production. This category refers to cases formerly classified as mucinous bronchioloalveolar carcinoma, excluding cases that meet the criteria for adenocarcinoma in situ or mucinous minimally invasive adenocarcinoma.
Plasma obtained from a patient who undergoes plasma exchange (also called therapeutic plasmapheresis).
A score assigned to a Curie body segment to indicate the quantity of metastases.
Blood or blood product donations intended for transfusion at a later time to the donor.
Another blood form product type other than the ones that are explicitly identified in this value set.
A neurodegenerative condition characterized by asymmetric weakness in the upper extremities resulting from segmental lower motor neuron dysfunction.
A subjective score of 10 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
The reemergence of anaplastic astrocytoma after a period of remission.
Problem associated with the ability of two or more devices which are intended to be incompatible but are able to work or fit together.
The reemergence of soft tissue sarcoma after a period of remission.
A junctional or compound melanocytic neoplasm not fulfilling the histopathologic criteria of melanoma but with one of the following features: asymmetry, predominance of single melanocytes over nests in lesions 4 mm or larger, ulceration, large dermal sheets of melanocytes, lack of maturation in dermis, deep dermal mitotic figures, extensive involvement of subcutis, and nuclear pleomorphism. (Mod Pathol 2006;19: S21)
Blood or blood product donations intended for transfusion to other than the donor.
Individual components, e.g. cryoprecipitated antihemophilic factor (AHF), whole blood-derived platelet concentrates, that are combined using an aseptic technique.
A response indicating that an individual needed very little assistance.
Vulvar cancer with regional lymph node metastasis with one or two lymph node metastases each less than 5 mm. It includes micrometastasis, N1mi. (from AJCC 8th Ed.)
Vulvar cancer with one lymph node metastasis equal to 5 mm. (from AJCC 8th Ed.)
Vulvar cancer with three or more lymph node metastases each less than 5 mm. It includes micrometastasis, N2mi. (from AJCC 8th Ed.)
Vulvar cancer with two or more lymph node metastases equal to 5 mm. (from AJCC 8th Ed.)
Vulvar cancer with tumor of any size with extension to any of the following: upper/proximal two-thirds of the urethra, upper/proximal two-thirds of the vagina, bladder mucosa, or rectal mucosa; or fixed to pelvic bone. (from AJCC 8th Ed.)
Vulvar cancer with fixed or ulcerated regional lymph node metastasis. (from AJCC 8th Ed.)
An intended site for a dose form that is for administration by injection.
An intended site for a dose form that is for administration to the respiratory tract.
A subjective score of 2 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
Reproductive Human Cells, Tissues and Tissue based Products (HCT/Ps) donated by a donor to a recipient who doesn't know and isn't known by the recipient before donation.
A response indicating that something happens or happened for a medium amount of time.
A response indicating that something is or was of a moderate amount, intensity, or duration.
A change in the nucleotide sequence of the APC gene.
The replacement of cortical bone by fibrous connective tissue that may be caused by parathyroid hormone-mediated bone resorption with secondary fibroplasia.
A subjective score of 3 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
A cytogenetic abnormality that involves a translocation between chromosomes 2 and 5.
Problems is not adequately described by any other term.
The concluded cause is not adequately described by any other term.
Problem associated with the complete inability to provide suction.
A subjective score of 7 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
A subjective score of 9 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
An autosomal dominant skeletal dysplasia caused by mutation(s) in the PRKAR1A gene, encoding cAMP-dependent protein kinase type I-alpha regulatory subunit. It is characterized by short stature, brachydactyly, and characteristic facial features. Resistance to multiple hormones is a common finding.
Donations from a donor called by the collecting facility to provide products for a specific recipient in some future therapeutic procedure, e.g. specifically matched blood for patients with antibodies.
Urine has an increased amount of frothy fine bubbles.
A diffuse large B-cell lymphoma characterized by double expression of MYC and BCL2 proteins without MYC and BCL2 gene aberrations. These lymphomas may have a worse prognosis than other diffuse large B-cell lymphomas, not otherwise specified, but they are not as aggressive as the high-grade B-cell lymphomas, with rearrangements of MYC and BCL2 and/or BCL6 genes.
A localized low-grade follicular lymphoma within the gastrointestinal tract, which is distinct from other gastrointestinal tract follicular lymphomas. It has features that overlap with in situ follicular neoplasia as well as some features resembling an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The prognosis is excellent.
A follicular neoplasia confined to the germinal centers of the lymph nodes, without evidence of disseminated disease. It is characterized by the replacement of a germinal center by neoplastic centrocytes with uniformly intense positivity for BCL2. The surrounding mantle cuff and lymphoid architecture are intact. It has a low rate of progression to follicular lymphoma, but is often associated with prior or synchronous overt lymphoma.
A rare B-cell non-Hodgkin lymphoma that is characterized by the abnormal rearrangement of MYC gene, BCL2 gene, and/or BCL6 gene. Patients with this type of lymphoma usually respond poorly to standard treatments and have a poor prognosis.
An orally available small molecule inhibitor of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK) with potential antineoplastic activity. Upon oral administration, ensartinib binds to and inhibits ALK kinase, ALK fusion proteins and ALK point mutation variants. Inhibition of ALK leads to the disruption of ALK-mediated signaling and eventually inhibits tumor cell growth in ALK-expressing tumor cells. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development. ALK is not expressed in healthy adult human tissue but ALK dysregulation and gene rearrangements are associated with a series of tumors; ALK mutations are associated with acquired resistance to small molecule tyrosine kinase inhibitors.
An orally available formulation containing an inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK), with potential antineoplastic activity. Upon administration, tirabrutinib covalently binds to BTK within B cells, thereby preventing B cell receptor signaling and impeding B cell development. As a result, this agent may inhibit the proliferation of B cell malignancies. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
Tumor involves adnexa. No regional lymph node or distant metastasis.
Tumor involves other pelvic tissues. No regional lymph node or distant metastasis.
An orally available, tropomyosin receptor kinase (Trk) inhibitor, with potential antineoplastic activity. Upon administration, larotrectinib binds to Trk, thereby preventing neurotrophin-Trk interaction and Trk activation, which results in both the induction of cellular apoptosis and the inhibition of cell growth in tumors that overexpress Trk. Trk, a receptor tyrosine kinase activated by neurotrophins, is mutated in a variety of cancer cell types and plays an important role in tumor cell growth and survival.
An elevated concentration of alkaline phosphatase in the urine.
A small molecule, competitive inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), with potential antineoplastic and chemoprotective activities. Upon intravenous administration, trilaciclib binds to and inhibits the activity of CDK4/6, thereby blocking the phosphorylation of the retinoblastoma protein (Rb) in early G1. This prevents G1/S phase transition, causes cell cycle arrest in the G1 phase, induces apoptosis, and inhibits the proliferation of CDK4/6-overexpressing tumor cells. In patients with CDK4/6-independent tumor cells, G1T28 may protect against multi-lineage chemotherapy-induced myelosuppression (CIM) by transiently and reversibly inducing G1 cell cycle arrest in hematopoietic stem and progenitor cells (HSPCs) and preventing transition to the S phase. This protects all hematopoietic lineages, including red blood cells, platelets, neutrophils and lymphocytes, from the DNA-damaging effects of certain chemotherapeutics and preserves the function of the bone marrow and the immune system. CDKs are serine/threonine kinases involved in the regulation of the cell cycle and may be overexpressed in certain cancer cell types. HSPCs are dependent upon CDK4/6 for proliferation.
A finding about one or more characteristics of nasal cavity and paranasal sinuses cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to malignancies that arise in the epithelial lining of the nasal cavity and paranasal sinuses, with the exception of lymphoma and sarcoma. Mucosal melanoma of the nasal cavity and paranasal sinuses is staged according to the classification for mucosal melanoma of the head and neck. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of nasal cavity and paranasal sinuses cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of nasal cavity and paranasal sinuses cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of maxillary sinus cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of nasal cavity and ethmoid sinus cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of nasal cavity and paranasal sinuses cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A clinical finding about one or more characteristics of nasal cavity and paranasal sinuses cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A pathologic finding about one or more characteristics of nasal cavity and paranasal sinuses cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of nasal cavity and paranasal sinuses cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Maxillary sinus cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Maxillary sinus cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Maxillary sinus cancer with tumor limited to the maxillary sinus mucosa with no erosion or destruction of bone. (from AJCC 8th Ed.)
Maxillary sinus cancer with tumor causing bone erosion or destruction including extension into the hard palate and/or middle nasal meatus, except extension to posterior wall of maxillary sinus and pterygoid plates. (from AJCC 8th Ed.)
Maxillary sinus cancer with tumor invading any of the following: bone of the posterior wall of maxillary sinus, subcutaneous tissues, floor or medial wall of orbit, pterygoid fossa, or ethmoid sinuses. (from AJCC 8th Ed.)
Maxillary sinus cancer with moderately advanced or very advanced local disease. (from AJCC 8th Ed.)
Maxillary sinus cancer with moderately advanced local disease. Tumor invades anterior orbital contents, skin of cheek, pterygoid plates, infratemporal fossa, cribriform plate, sphenoid or frontal sinuses. (from AJCC 8th Ed.)
Maxillary sinus cancer with very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx, or clivus. (from AJCC 8th Ed.)
Nasal cavity and ethmoid sinus cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Nasal cavity and ethmoid sinus cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Nasal cavity and ethmoid sinus cancer with tumor restricted to any one subsite, with or without bony invasion. (from AJCC 8th Ed.)
Nasal cavity and ethmoid sinus cancer with tumor invading two subsites in a single region or extending to involve an adjacent region within the nasoethmoidal complex, with or without bony invasion. (from AJCC 8th Ed.)
Nasal cavity and ethmoid sinus cancer with tumor invading the medial wall or floor of the orbit, maxillary sinus, palate, or cribriform plate. (from AJCC 8th Ed.)
Nasal cavity and ethmoid sinus cancer with moderately advanced or very advanced local disease. (from AJCC 8th Ed.)
Nasal cavity and ethmoid sinus cancer with moderately advanced local disease. Tumor invades any of the following: anterior orbital contents, skin of nose or cheek, minimal extension to anterior cranial fossa, pterygoid plates, sphenoid or frontal sinuses. (from AJCC 8th Ed.)
Nasal cavity and ethmoid sinus cancer with very advanced local disease. Tumor invades any of the following: orbital apex, dura, brain, middle cranial fossa, cranial nerves other than maxillary division of trigeminal nerve (V2), nasopharynx, or clivus. (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a single ipsilateral lymph node, larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes , none larger than 6 cm in greatest dimension and ENE(-); or in in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-) . (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a single ipsilateral lymph node, larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-) . (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in any node(s) with clinically overt ENE(+) . (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in any node(s) with clinically overt ENE(+) (ENEc). (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes , none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a single ipsilateral or contralateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral or bilateral nodes, any with ENE(+) . (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with metastasis in a single ipsilateral node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral or bilateral nodes, any with ENE(+) . (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Nasal cavity and paranasal sinuses cancer with distant metastasis. (from AJCC 8th Ed.)
A preparation of genetically modified central memory (Tcm) enriched T-cells transduced with a replication incompetent lentiviral vector expressing a chimeric antigen receptor (CAR), containing a CD28 signaling domain fused to both CD3 zeta, which targets the CD19 antigen, and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells are directed to CD19-expressing tumor cells, thereby inducing a selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, EGFRt both facilitates in vivo detection of the administered T-cells and can promote elimination of those cells upon a cetuximab-induced antibody dependent cellular cytotoxicity response. The costimulatory signaling domain enhances proliferation of T cells and antitumor activity.
A term that refers to the staging of nasal cavity and paranasal sinus carcinoma according to the American Joint Committee on Cancer, 8th edition.
Globoid cell leukodystrophy that occurs in a dog.
Pancreatic ductal carcinoma that occurs in a hamster.
A very rare benign neoplasm that arises from the lung. It is characterized by the presence of a stromal and an epithelial component. It resembles the adenofibromas that arise from the organs of the female reproductive system.
The reemergence of breast angiosarcoma after a period of remission.
A solid neoplasm that has spread from its original site of growth to nearby tissues or lymph nodes.
A finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to the supraglottic, glottic, and subglottic laryngeal cancers. Nonepithelial cancers such as those of lymphoid tissue, soft tissue, bone, and cartilage are not included in this classification. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of supraglottic cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Supraglottic cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Supraglottic cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Supraglottic cancer with tumor limited to one subsite of supraglottis with normal vocal cord mobility. (from AJCC 8th Ed.)
Supraglottic cancer with tumor invading the mucosa of more than one adjacent subsite of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of the tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx. (from AJCC 8th Ed.)
Supraglottic cancer with tumor limited to larynx with vocal cord fixation and/or invading any of the following: postcricoid area, preepiglottic space, paraglottic space, and/or inner cortex of thyroid cartilage. (from AJCC 8th Ed.)
Supraglottic cancer with moderately advanced or very advanced disease. (from AJCC 8th Ed.)
Supraglottic cancer with moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 8th Ed.)
Supraglottic cancer with very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of glottic cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Glottic cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Glottic cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Glottic cancer with tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility. (from AJCC 8th Ed.)
Glottic cancer with tumor limited to one vocal cord. (from AJCC 8th Ed.)
Glottic cancer with tumor involving both vocal cords. (from AJCC 8th Ed.)
Glottic cancer with tumor extending to supraglottis and/or subglottis, and/or with impaired vocal cord mobility. (from AJCC 8th Ed.)
Glottic cancer with tumor limited to the larynx with vocal cord fixation and /or invasion of paraglottic space, and/or inner cortex of the thyroid cartilage. (from AJCC 8th Ed.)
Glottic cancer with moderately advanced or very advanced disease. (from AJCC 8th Ed.)
Glottic cancer with moderately advanced local disease. Tumor invades through the outer cortex of the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, cricoid cartilage, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 8th Ed.)
Glottic cancer with very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of subglottic cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Subglottic cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Subglottic cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Subglottic cancer in which the tumor is limited to the subglottis. (from AJCC 8th Ed.)
Subglottic cancer with tumor extending to vocal cord(s) with normal or impaired mobility. (from AJCC 8th Ed.)
Subglottic cancer with tumor limited to the larynx with vocal cord fixation and/or invasion of paraglottic space and/or inner cortex of the thyroid cartilage. (from AJCC 8th Ed.)
Subglottic cancer with moderately advanced or very advanced disease. (from AJCC 8th Ed.)
Subglottic cancer with moderately advanced local disease. Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). (from AJCC 8th Ed.)
Subglottic cancer with very advanced local disease. Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Laryngeal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Laryngeal cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-); or metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Laryngeal cancer with metastases in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a lymph node, more than 6 cm in greatest dimension and ENE(-); or metastasis in any lymph node(s) with clinically overt ENE(+). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a lymph node, more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in any lymph node(s) with clinically overt ENE(+). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-); or metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a single ipsilateral or contralateral lymph node, 3 cm or less in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a lymph node, more than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node, more than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes and any with ENE(+). (from AJCC 8th Ed.)
Laryngeal cancer with metastasis in a single ipsilateral lymph node, more than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes and any with ENE(+). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Laryngeal cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Laryngeal cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A term that refers to the staging of laryngeal carcinoma according to the American Joint Committee on Cancer, 8th edition.
DNA sequence rearrangements that are detected or characterized by presence of a single type of protein molecule in a cell population.
DNA sequence rearrangements that are detected or characterized by presence of multiple types of protein molecules in a cell population.
A finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v8 classification system. It applies to mucosal melanomas arising in the nasal cavity, paranasal sinuses, oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx. No prognostic stage grouping is proposed in AJCC 8th edition. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Mucosal melanoma of the head and neck without evidence of distant metastasis. (from AJCC 8th Ed.)
Mucosal melanoma of the head and neck with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v8 classification system.
An inhibitor of induced myeloid leukemia cell differentiation protein (Mcl-1; Bcl2-L-3), with potential pro-apoptotic and antineoplastic activities. Upon administration, MIK665 binds to and inhibits the activity of Mcl-1, which promotes apoptosis of cells overexpressing Mcl-1. Mcl-1, an anti-apoptotic protein belonging to the Bcl-2 family of proteins, is upregulated in cancer cells and promotes tumor cell survival.
A pathologic finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Mucosal melanoma of the head and neck with tumor limited to the mucosa and immediately underlying soft tissue, regardless of thickness or greatest dimension; for example, polypoid nasal disease, pigmented or nonpigmented lesions of the oral cavity, pharynx, or larynx. (from AJCC 8th Ed.)
Mucosal melanoma of the head and neck with moderately advanced or very advanced disease. (from AJCC 8th Ed.)
Mucosal melanoma of the head and neck with moderately advanced disease. Tumor involves deep soft tissue, cartilage, bone, or overlying skin. (from AJCC 8th Ed.)
Mucosal melanoma of the head and neck with very advanced disease. Tumor involves brain, dura, skull base, lower cranial nerves (IX, X, XI, XII), masticator space, carotid artery, prevertebral space, or mediastinal structures. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of mucosal melanoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Mucosal melanoma of the head and neck with no metastases to regional lymph nodes. (from AJCC 8th Ed.)
Mucosal melanoma of the head and neck with regional lymph node metastases. (from AJCC 8th Ed.)
A term that refers to the staging of mucosal melanoma of the head and neck according to the American Joint Committee on Cancer, 7th edition. No prognostic stage grouping is proposed in the 8th edition.
A melanoma that arises in the mucosa of the nasal cavity, paranasal sinuses, oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx.
A radioimmunoconjugate containing the murine IgG1 anti-CD45 monoclonal antibody (MAb) BC8 where the lysine side groups have been conjugated with decaborate (closo-decaborate; B10) and labeled with astatine (At) 211, with potential immunotherapeutic activity. Astatine At 211 anti-CD45 monoclonal antibody BC8-B10 binds to CD45 antigen, a receptor protein-tyrosine phosphatase expressed on the surface of both normal and malignant hematopoietic cells. After binding and internalization by CD45-expressing tumor cells, this agent may deliver a cytotoxic dose of alpha radiation. Additionally, the radiolabel can be leveraged to assay the biodistribution and/or pharmacokinetics (absorption, distribution, metabolism and excretion) for this agent. The use of B10 rather than other labeling methods increases the therapeutic efficacy while decreasing the toxicity of the radioconjugate.
A precancerous neoplastic process affecting the oral mucosa. It is characterized by the presence of dysplasia in the mucosal epithelium.
A carcinoma of the thyroid gland that has spread to another anatomic site.
A finding about one or more characteristics of cutaneous squamous cell carcinoma of the head and neck, following the rules of the TNM AJCC v8 classification system. It applies to cutaneous squamous cell carcinoma of the head and neck and all other nonmelanoma skin carcinomas of the head and neck (except Merkel cell carcinoma). It also applies to the adenocarcinomas that develop from eccrine or sebaceous glands and to the spindle cell variant of cutaneous squamous cell carcinoma. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of cutaneous squamous cell carcinoma of the head and neck, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of cutaneous squamous cell carcinoma of the head and neck, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of cutaneous squamous cell carcinoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Cutaneous squamous cell carcinoma of the head and neck without evidence of distant metastasis. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of cutaneous squamous cell carcinoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of cutaneous squamous cell carcinoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Cutaneous squamous cell carcinoma of the head and neck in which the primary tumor cannot be identified. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with tumor smaller than 2 cm in greatest dimension. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with tumor 2 cm or larger, but smaller than 4 cm in greatest dimension. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with tumor 4 cm or larger in greatest dimension or minor bone erosion or perineural invasion or deep invasion. Deep invasion is defined as invasion beyond the subcutaneous fat or larger than 6 mm; perineural invasion for T3 classification is defined as tumor cells within the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in caliber, or presenting with clinical or radiographic involvement of named nerves without skull base invasion or transgression. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with gross cortical bone/marrow, skull base invasion and/or skull base foramen invasion. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with gross cortical bone/marrow invasion. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with skull base invasion and/or skull base foramen involvement. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of cutaneous squamous cell carcinoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Cutaneous squamous cell carcinoma of the head and neck in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck without metastasis in the regional lymph nodes. (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in any lymph node(s) and clinically overt ENE(+). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of cutaneous squamous cell carcinoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a single ipsilateral or contralateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes, any with ENE(+). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes, any with ENE(+). (from AJCC 8th Ed.)
Cutaneous squamous cell carcinoma of the head and neck with metastasis in any lymph node(s) and ENE(+). (from AJCC 8th Ed.)
An orally bioavailable, hydrated, tosylate salt form of niraparib, an inhibitor of poly (ADP-ribose) polymerase (PARP) types 1 and 2 (PARP-1 and -2), with antineoplastic activity. Upon administration, niraparib binds to and inhibits the activity of PARP-1 and -2, thereby inhibiting PARP-1 and -2-mediated DNA repair, enhancing the accumulation of DNA strand breaks, promoting genomic instability and resulting in apoptosis. The PARP family of proteins catalyzes post-translational ADP-ribosylation of nuclear proteins and is activated by single-strand DNA (ssDNA) breaks.
A squamous cell carcinoma that arises from the skin of the head and neck.
A term that refers to the staging of cutaneous squamous cell carcinoma of the head and neck according to the American Joint Committee on Cancer, 8th edition.
A squamous cell carcinoma that arises from the lung. It is characterized by the presence of large malignant cells. It includes the clear cell and papillary variants of squamous cell carcinoma.
Stage I includes: T1, N0, M0. T1: Tumor smaller than 2 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Tumor 2 cm or larger, but smaller than 4 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T3, N0, M0); (T1, N1, M0); (T2, N1, M0); (T3, N1, M0). T3: Tumor 4 cm or larger in greatest dimension or minor bone erosion or perineural invasion or deep invasion. Deep invasion is defined as invasion beyond the subcutaneous fat or larger than 6 mm; perineural invasion for T3 classification is defined as tumor cells within the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in caliber, or presenting with clinical or radiographic involvement of named nerves without skull base invasion or transgression. T1: Tumor smaller than 2 cm in greatest dimension. T2: Tumor 2 cm or larger, but smaller than 4 cm in greatest dimension. N0: No regional lymph node metastasis. N1: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(-). M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: (T1, N2, M0); (T2, N2, M0); (T3, N2, M0); (Any T, N3, M0); (T4, Any N, M0); (Any T, Any N, M1). T1: Tumor smaller than 2 cm in greatest dimension. T2: Tumor 2 cm or larger, but smaller than 4 cm in greatest dimension. T3: Tumor 4 cm or larger in greatest dimension or minor bone erosion or perineural invasion or deep invasion. Deep invasion is defined as invasion beyond the subcutaneous fat or larger than 6 mm; perineural invasion for T3 classification is defined as tumor cells within the nerve sheath of a nerve lying deeper than the dermis or measuring 0.1 mm or larger in caliber, or presenting with clinical or radiographic involvement of named nerves without skull base invasion or transgression. T4: Tumor with gross cortical bone/marrow, skull base invasion and/or skull base foramen invasion. N2: Metastasis in a single ipsilateral lymph node, 3 cm or smaller in greatest dimension and ENE(+); or metastasis in a single ipsilateral lymph node larger than 3 cm but not larger than 6 cm in greatest dimension and ENE(-); or metastases in multiple ipsilateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-); or metastases in bilateral or contralateral lymph nodes, none larger than 6 cm in greatest dimension and ENE(-). N3: Metastasis in a lymph node larger than 6 cm in greatest dimension and ENE(-); or metastasis in a single ipsilateral lymph node larger than 3 cm in greatest dimension and ENE(+); or metastases in multiple ipsilateral, contralateral, or bilateral lymph nodes, any with ENE(+). M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Donations arranged by the collecting facility to support a specific recipient on a frequent basis.
Whole blood, red blood cells, or platelets intended for diagnostic use.
Cells from human blood or umbilical cord blood for transplantation or infusion.
White blood cells intended as source material for further manufacturing use.
Reproductive Human Cells, Tissues and Tissue based Products (HCT/Ps) donated by a donor to a recipient who is a sexually intimate partner.
The fluid portion of one unit of human blood intended for transfusion which has been separated from whole blood and placed at -18 degrees C or colder within 24 hours from whole blood collection. When prepared by automated apheresis the product is stored at 1 degree to 6 degrees C within 8 hours of collection and frozen at -18 degrees C or colder within 24 hours of collection.
Plasma Frozen within 24 Hours after Phlebotomy held at Room Temperature Up To 24 Hours after Phlebotomy (PF24RT24). Plasma prepared from automated apheresis collections can be held at room temperature for up 24 hours after collection and then frozen at -18 degrees C or colder.
Plasma derived from single units of whole blood, plasma, or as a by-product in the preparation of blood components from whole blood, for use in the manufacturing of licensed or unlicensed products.
Plasma from which cryoprecipitated antihemophilic factor (AHF) has been removed.
Single donor plasma separated from red donor cells within 26 days after phlebotomy (40 days when citrate phosphate dextrose adenine (CPDA-1) is used as the anticoagulant) and stored at 1-6 degrees C.
Platelets that have been tested for bacteria using an FDA-cleared rapid bacterial detection device labeled as a safety measure, following testing with a growth-based quality control test cleared by the FDA for platelet components, that can support extending the expiration date of platelets past 5 days.
Whole blood derived or apheresis collected platelets washed with normal saline or saline-buffered with acid citrate dextrose formula-A (ACD-A) or citrate using manual or automated methods. The washed platelets are stored at 20-24 degrees C for up to 4 hours.
Red blood cells washed free of the glycerol in which they have been stored.
Red blood cells stored at an ultra-low temperature in the presence of a cryoprotective agent. These may be preserved for long periods of time.
Red blood cells treated with a rejuvenating solution, then frozen and stored at ultra-low temperatures in the presence of a cryoprotective agent.
Red blood cells to which plasma is added to prepare a whole blood product, often with a designated specific hematocrit.
Red blood cells treated with a rejuvenating solution, then frozen using a cryoprotective agent, and finally, washed free of the rejuvenating solution and glycerol.
Red blood cells treated to restore cell integrity with a rejuvenating solution, such as pyruvate inosine.
Red blood cells typically washed using normal saline with or without small amounts of dextrose using manual or automated methods. The washed red blood cells are stored at 1-6 degrees C for up to 24 hours.
A finding about one or more characteristics of digestive system cancer, following the rules of the TNM AJCC v8 classification system.
Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from the human heart.
A finding about one or more characteristics of upper gastrointestinal tract cancer, following the rules of the TNM AJCC v8 classification system.
Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) from the human muscular and skeletal system.
A finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to carcinomas including squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, undifferentiated carcinoma, neuroendocrine cancers, and adenocarcinoma with neuroendocrine features. Sarcomas, nonepithelial cancers, and gastrointestinal stromal tumors are not staged using this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v8 classification system.
Esophagus and esophagogastric junction cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Esophagus and esophagogastric junction cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with a finding of high-grade dysplasia, defined as malignant cells confined to the epithelium by the basement membrane. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading the lamina propria, muscularis mucosae, or submucosa. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading the lamina propria or muscularis mucosae. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading the submucosa. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading the muscularis propria. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading adventitia. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading adjacent structures. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading the pleura, pericardium, azygos vein, diaphragm, or peritoneum. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with tumor invading other adjacent structures, such as the aorta, vertebral body, or airway. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of esophagus and esophagogastric junction cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Esophagus and esophagogastric junction cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with metastasis in one or two regional lymph nodes. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with metastasis in three to six regional lymph nodes. (from AJCC 8th Ed.)
Esophagus and esophagogastric junction cancer with metastasis in seven or more regional lymph nodes. (from AJCC 8th Ed.)
Location of esophageal squamous cell carcinoma is defined by the position of the epicenter of the tumor in the esophagus. Location plays a role in the stage grouping of esophageal squamous carcinomas. (from AJCC 8th Ed.)
Esophageal squamous cell carcinoma with unknown location. (from AJCC 8th Ed.)
Esophageal squamous cell carcinoma located in the cervical esophagus to lower border of azygos vein. (from AJCC 8th Ed.)
Esophageal squamous cell carcinoma located in the lower border of azygos vein to lower border of inferior pulmonary vein. (from AJCC 8th Ed.)
Esophageal squamous cell carcinoma located in the lower border of inferior pulmonary vein to stomach, including gastroesophageal junction. (from AJCC 8th Ed.)
Pathologic TNM staging performed with access to postneoadjuvant therapy information only.
A term that refers to the staging of esophageal carcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the staging of esophageal adenocarcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the clinical staging of esophageal adenocarcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the staging of esophageal adenocarcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the pathologic staging of esophageal adenocarcinoma according to the American Joint Committee on Cancer, 8th edition.
Stage IC includes: (T1, N0, M0, G3); (T2, N0, M0, G1-2). T1: Tumor invades the lamina propria, muscularis mucosae, or submucosa. T2: Tumor invades the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. G1: Well-differentiated. G2: Moderately differentiated. G3: Poorly differentiated, undifferentiated. (AJCC 8th ed.)
Locoregional neuroblastoma without image defined risk factors (IDRFs).
Locoregional neuroblastoma with one or more image defined risk factors (IDRFs).
Neuroblastoma with distant metastatic disease (except MS).
INRG stage L1 or L2 neuroblastoma with metastatic disease confined to the skin and/or liver and/or bone marrow.
A term that refers to the postneoadjuvant therapy staging of esophageal adenocarcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the staging of esophageal squamous cell carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of esophageal squamous cell carcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the pathologic staging of esophageal squamous cell carcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the postneoadjuvant therapy staging of esophageal squamous cell carcinoma according to the American Joint Committee on Cancer, 8th edition.
A variation in the amino acid sequence for the ALK tyrosine kinase receptor protein.
A change in the amino acid residue at position 1170 in the ALK tyrosine kinase receptor protein where arginine has been replaced by another amino acid.
A change in the amino acid residue at position 1174 in the ALK tyrosine kinase receptor protein where phenylalanine has been replaced by another amino acid.
A change in the amino acid residue at position 1245 in the ALK tyrosine kinase receptor protein where phenylalanine has been replaced by another amino acid.
A score assigned to a Curie body segment to indicate the strength of 123I-mIBG uptake.
More than one metastatic site within a segment.
Diffuse involvement within a segment (>50% of the segment).
Definite uptake within a segment, but less uptake than in the liver.
A nucleotide substitution at position 3509 of the coding sequence of the ALK gene where thymine has been mutated to adenine.
Intense uptake, greater than in the liver.
A change in the amino acid residue at position 1170 in the ALK tyrosine kinase receptor protein where isoleucine has been replaced by asparagine.
A nucleotide substitution at position 3509 of the coding sequence of the ALK gene where thymine has been mutated to guanine.
A change in the amino acid residue at position 1170 in the ALK tyrosine kinase receptor protein where isoleucine has been replaced by serine.
A nucleotide substitution at position 3512 of the coding sequence of the ALK gene where thymine has been mutated to adenine.
A complex nucleotide substitution where the nucleotide sequence at positions 3512 and 3513 of the coding sequence of the ALK gene where thymine-cytosine has been mutated to adenine-thymine.
A nucleotide substitution at position 3833 of the coding sequence of the ALK gene where adenine has been mutated to cytosine.
A change in the amino acid residue at position 1278 in the ALK tyrosine kinase receptor protein where tyrosine has been replaced by serine.
A nucleotide substitution at position 3575 of the coding sequence of the ALK gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 1192 in the ALK tyrosine kinase receptor protein where arginine has been replaced by proline.
A nucleotide substitution at position 3497 of the coding sequence of the ALK gene where thymine has been mutated to guanine.
A change in the amino acid residue at position 1166 in the ALK tyrosine kinase receptor protein where methionine has been replaced by arginine.
A nucleotide substitution at position 3586 of the coding sequence of the ALK gene where cytosine has been mutated to adenine.
A change in the amino acid residue at position 1196 in the ALK tyrosine kinase receptor protein where leucine has been replaced by methionine.
A nucleotide substitution at position 3383 of the coding sequence of the ALK gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 1128 in the ALK tyrosine kinase receptor protein where glycine has been replaced by alanine.
A large B-cell lymphoma typically affecting the Waldeyer ring and/or cervical lymph nodes. It occurs most commonly in children and young adults and is low stage. It is characterized by a follicular, follicular and diffuse, or pure diffuse growth pattern resembling follicular lymphoma grade 3B or a diffuse large B-cell lymphoma. Most cases have IG/IRF4 rearrangements. BCL2 rearrangements are not present. Some cases that belong in this category lack an IRF4 rearrangement but have strong IRF4/MUM1 expression. This lymphoma is more aggressive than pediatric-type follicular lymphomas.
A molecular abnormality indicating rearrangement of the IRF4 gene.
Problem associated with the loss of direct anchorage of an implanted device over time or due to an injury.
A device is found to have one or more components incorrectly assembled when delivered to the user facility.
A carcinoma that has spread to the central nervous system from its original site in the breast, through the hematogenous route.
A carcinoma that has spread to the central nervous system from its original site in the lung, through the hematogenous route.
A melanoma that has spread to the central nervous system from its original site of growth, through the hematogenous route.
Problem associated with the device material that results in the material's inability to maintain the desired shape or support function.
Problem associated with materials comprising the device are split, cut or torn due to external forces (e.g. wrenching or laceration) or internal forces (e.g. exceeding the tensile stress limits belonging to the materials used in the device construction).
Problems associated with the inability of or unexpected removal or separation of the device from its physical location.
Problem associated with the inability to remove or discharge device from the location of use.
Problem associated with the device not discharging as intended.
Problem associated with the lack of movement in the device due parts sticking or seizing.
The device has undesirable sharp edges which can cause harm or damage.
Problem associated with the device or a component unexpectedly being dropped or moving down from an intended place.
Problem associated with the lack of power to run a device.
Problem associated with an intermittent disruption to the power to run the device.
The device delivers unintended electrical shock.
An orally available inhibitor of PIM family serine/threonine protein kinases and mutant forms of FMS-related tyrosine kinase 3 (FLT3; STK1) with potential antineoplastic activity. PIM/FLT3 kinase inhibitor SEL24 binds to and inhibits the kinase activities of PIM-1, -2 and -3, and mutant forms of FLT3, which may result in the interruption of the G1/S phase cell cycle transition, an inhibition of cell proliferation, and an induction of apoptosis in tumor cells that overexpress PIMs or express mutant forms of FLT3. FLT3, a tyrosine kinase receptor that is overexpressed or mutated in various cancers, plays a role in signaling pathways that regulate hematopoietic progenitor cell proliferation, and in leukemic cell proliferation and survival. PIM kinases, downstream effectors of many cytokine and growth factor signaling pathways, including the FLT3 signaling pathway, play key roles in cell cycle progression and apoptosis inhibition and may be overexpressed in various malignancies.
A humanized monoclonal immunoglobulin G1 anti-P-selectin antibody with vaso-protective and anti-vaso-occlusive properties. Upon administration, crizanlizumab binds to P-selectin and blocks its interaction with P-selectin glycoprotein ligand-1 (PSGL-1; SELPLG) on neutrophils and monocytes. P-selectin, a glycoprotein that functions as a cell adhesion molecule (CAM), translocates to the surface of activated endothelial cells and platelets, upon stimulation, where it binds to its ligand and mediates the rolling of platelets and neutrophils on activated endothelial cells. Therefore, blockade of p-selectin may inhibit platelet aggregation, maintain blood flow and minimize sickle cell-related pain crises (SCPC).
Problem associated with the device unexpectedly powering down.
Problem with any deviation from the documented specifications of a device that relates to audible feedback.
Problem associated with the device ceasing to provide visual feedback.
Problem with any deviation from the documented specifications of the device that relates to tactile feedback, e.g. device vibrational prompt.
A term that refers to the staging of gastroesophageal junction adenocarcinoma according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the clinical staging of gastroesophageal junction adenocarcinoma according to the American Joint Committee on Cancer, 8th edition.
Problem with tactile feedback which does not guide a device user to the correct action.
Problem associated with the device ceasing to provide tactile feedback.
Problem associated with the energy output from the device being inconsistent over time.
Problem with the device's intended output of radiation.
A term that refers to the pathologic staging of gastroesophageal junction adenocarcinoma according to the American Joint Committee on Cancer, 8th edition.
Problem associated with the absence of radiation output from radiological or diagnostic devices.
Device-emitted radiation when it was not supposed to. This applies to devices which are intended to emit radiation, and the radiation being emitted from the correct part of the device, but at an incorrect time.
Device results that cannot be reliably reproduced.
Problem associated with the device which has a warming or heating function, and is producing excessive heat.
Problem associated with freezing and becoming nonfunctional of an application program.
A term that refers to the postneoadjuvant therapy staging of gastroesophageal junction adenocarcinoma according to the American Joint Committee on Cancer, 8th edition.
The reemergence of classical Hodgkin lymphoma after a period of remission.
Problem associated with execution problems relating to program or algorithm.
Problem associated with an unintended shut down by malfunction of the application program.
A finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to all carcinomas that arise in the stomach. Gastrointestinal stromal tumors, sarcomas, lymphomas and well-differentiated neuroendocrine tumors (G1 and G2) are not staged using this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Gastric cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Problem associated with a delayed execution relating to program or algorithm.
Gastric cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Problem associated with intermittent execution relating to program or algorithm.
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Gastric cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Gastric cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Gastric cancer with a finding of carcinoma in situ: intraepithelial tumor without invasion of the lamina propria, high grade dysplasia. (from AJCC 8th Ed.)
Gastric cancer with tumor invading the lamina propria, muscularis mucosae, or submucosa. (from AJCC 8th Ed.)
Gastric cancer with tumor invading the lamina propria or muscularis mucosae. (from AJCC 8th Ed.)
Gastric cancer with tumor invading the submucosa. (from AJCC 8th Ed.)
Gastric cancer with tumor invading the muscularis propria. A tumor may penetrate the muscularis propria with extension into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum, without perforation of the visceral peritoneum covering these structures. In this case, the tumor is classified as T3. If there is perforation of the visceral peritoneum covering the gastric ligaments or the omentum, the tumor should be classified as T4. (from AJCC 8th Ed.)
Gastric cancer with tumor penetrating the subserosal connective tissue without invasion of the visceral peritoneum or adjacent structures. The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. Intramural extension to the duodenum or esophagus is not considered invasion of an adjacent structure, but is classified using the depth of the greatest invasion in any of these sites. (from AJCC 8th Ed.)
Gastric cancer with tumor invading the serosa (visceral peritoneum) or adjacent structures. The adjacent structures of the stomach include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine, and retroperitoneum. Intramural extension to the duodenum or esophagus is not considered invasion of an adjacent structure, but is classified using the depth of the greatest invasion in any of these sites. (from AJCC 8th Ed.)
Gastric cancer with tumor invading the serosa (visceral peritoneum). (from AJCC 8th Ed.)
Gastric cancer with tumor invading adjacent structures/organs. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of gastric cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Gastric cancer in which the regional lymph node(s) cannot be assessed. (from AJCC 8th Ed.)
Gastric cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Gastric cancer with metastasis in one or two regional lymph nodes. (from AJCC 8th Ed.)
Gastric cancer with metastasis in three to six regional lymph nodes. (from AJCC 8th Ed.)
Gastric cancer with metastasis in seven or more regional lymph nodes. (from AJCC 8th Ed.)
Gastric cancer with metastasis in seven to fifteen regional lymph nodes. (from AJCC 8th Ed.)
Gastric cancer with metastasis in sixteen or more regional lymph nodes. (from AJCC 8th Ed.)
Problem associated with the failure of a program or algorithm to execute. Sudden /unexpected interruption to a program's execution.
Problem associated with a partial linking of the device whereby the device may appear to be connected however only a partial, intermittent or no transfer of liquid, gas, electricity, or information can be accomplished.
Inconsistent or lack of intended communication of data among internal components or with other external devices.
Problem associated with the preparation of the device to begin pumping.
Problem associated with not adequately preparing the device.
Problem associated with the activation of a device.
Problem associated with the detachment or separation of device.
Problem associated with users experiencing difficulty or delay with detachment or separation of the device.
Problem associated with an early and unexpected detachment or separation of the device from the system.
Problem associated with the device fail-safe mechanism, which did not function or function in a non effective way, compromising safe use of the device.
Problem associated with the failure of the device or operator to remove any visible soil, foreign material or organism deposits on the external surfaces, crevices, and joints of the device.
A term that refers to the staging of gastric cancer according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the clinical staging of gastric cancer according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the pathologic staging of gastric cancer according to the American Joint Committee on Cancer, 8th edition.
A term that refers to the postneoadjuvant therapy staging of gastric cancer according to the American Joint Committee on Cancer, 8th edition.
Problem associated with information unable to be read or deciphered.
Problem associated with imprecise, inexact information.
Problem associated with ambiguous, confusing information.
Absence of information e.g. labeling, instruction for use.
Problem associated with incorrect assembly of the device or constituents during maintenance or repair.
Stage IVA includes: (T4b, Any N, M0): T4b: Tumor invades adjacent structures/organs. M0: No distant metastasis. (AJCC 8th ed.)
A change in the nucleotide sequence of the PTCH1 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the BRAF gene.
A molecular genetic abnormality indicating the presence of multiple copies of the RAF1 gene.
A change in the nucleotide sequence of the RAF1 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the RET gene.
A molecular genetic abnormality indicating the presence of multiple copies of the KIT gene.
A molecular abnormality referring to the loss of at least one copy of the ATM gene.
A change in the nucleotide sequence of the EPHA2 gene.
A change in the nucleotide sequence of the FYN gene.
A change in the nucleotide sequence of the YES1 gene.
A change in the nucleotide sequence of the MTOR gene.
A change in the nucleotide sequence of the CSF1R gene.
A change in the nucleotide sequence of the SRC gene.
A change in the nucleotide sequence of the LCK gene.
A change in the nucleotide sequence of the LYN gene.
An orally available inhibitor of the epidermal growth factor receptor (EGFR) mutant form T790M, with potential antineoplastic activity. Upon administration, HS-10296 binds to and inhibits EGFR T790M, a secondarily acquired resistance mutation, inhibits the tyrosine kinase activity of EGFR T790M, prevents EGFR T790M-mediated signaling and leads to cell death in EGFR T790M-expressing tumor cells. EGFR, a receptor tyrosine kinase that is mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
A molecular abnormality indicating the presence of an abnormally high level of the Myc proto-oncogene protein.
A cytogenetic abnormality that refers to any translocation involving the long arm of chromosome 11.
A molecular abnormality referring to the loss of at least one copy of the TP53 gene.
A change in the nucleotide sequence of a gene involved in homologous recombination-type DNA repair processes.
A change in the nucleotide sequence of the RB1 gene.
A molecular abnormality indicating rearrangement of the TFE3 gene.
A change in the nucleotide sequence of the SRSF2 gene.
A molecular abnormality referring to the loss of at least one copy of the SRSF2 gene.
A change in the nucleotide sequence of the U2AF1 gene.
A change in the nucleotide sequence of the ZRSR2 gene.
A change in the nucleotide sequence of the SF3B1 gene.
A change in the nucleotide sequence of a gene involved in DNA mismatch repair.
The reemergence of squamous cell carcinoma in the head and neck region after a period of remission.
A paraganglioma that has spread from its original site of growth to another anatomic site.
A paraganglioma that has spread from its original site of growth to nearby tissues or lymph nodes.
A term that refers to the staging of small intestinal cancer according to the American Joint Committee on Cancer, 7th edition.
The mesylate salt form of alflutinib, an orally available selective inhibitor of the epidermal growth factor receptor (EGFR) mutant form T790M, with potential antineoplastic activity. Upon administration, alflutinib specifically binds to and inhibits the tyrosine kinase activity of EGFR T790M, a secondarily acquired resistance mutation. This prevents EGFR T790M-mediated signaling and leads to cell death in EGFR T790M-expressing tumor cells. EGFR, a receptor tyrosine kinase that is mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. Compared to some other EGFR inhibitors, alflutinib may have therapeutic benefits in tumors with T790M-mediated drug resistance.
An orally bioavailable capsule formulation of the inorganic toxic compound arsenic trioxide (As2O3), with potential antineoplastic activity. Although the mechanism of action (MoA) of As2O3 is not well understood, upon oral administration of ORH 2014, As2O3 appears to bind to DNA, prevent DNA synthesis, and cause DNA fragmentation, which leads to an induction of apoptosis in proliferating cells, including tumor cells. In addition, As2O3 causes damage to and induces degradation of the promyelocytic leukemia protein/retinoic acid receptor-alpha (PML/RARa) fusion protein, and inhibits the activity of the enzyme thioredoxin reductase.
Problem associated with the use of the device characterized by incorrect assembly of device components, parts or constituents.
Primary amyloidosis that does not respond to treatment.
Reemergence of primary amyloidosis after a period of remission.
A term that refers to the staging of appendiceal carcinoma according to the American Joint Committee on Cancer, 7th edition. Carcinoid tumors are staged separately. (from AJCC 7th Ed.)
Classical Hodgkin lymphoma that is resistant to treatment.
A malignant solid neoplasm that does not respond to treatment.
Oral cavity squamous cell carcinoma that occurs in a rabbit.
Cutaneous lymphoma that occurs in a rabbit.
A finding about one or more characteristics of lower gastrointestinal tract cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Anal cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Anal cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Anal cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Anal cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Anal cancer with a finding of high-grade squamous intraepithelial lesion (previously termed carcinoma in situ, Bowen disease, anal intraepithelial neoplasia II-III, high-grade anal intraepithelial neoplasia). (from AJCC 8th Ed.)
Anal cancer with tumor 2 cm or smaller. (from AJCC 8th Ed.)
Anal cancer with tumor larger than 2 cm but equal to or smaller than 5 cm. (from AJCC 8th Ed.)
Anal cancer with tumor larger than 5 cm. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Anal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Anal cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Anal cancer with metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes. (from AJCC 8th Ed.)
Anal cancer with metastasis in inguinal, mesorectal, or internal iliac lymph nodes. (from AJCC 8th Ed.)
Anal cancer with metastasis in external iliac lymph nodes. (from AJCC 8th Ed.)
Anal cancer with metastasis in external iliac with any N1a nodes. (from AJCC 8th Ed.)
A term that refers to the staging of anal canal cancer according to the American Joint Committee on Cancer, 6th and 7th editions. This staging system applies to carcinomas arising in the anal canal only; melanomas, carcinoid tumors, sarcomas, and perianal tumors are not included. (from AJCC 6th and 7th Eds.)
A term that refers to the staging of anal cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to all carcinomas arising in the anal canal, including carcinomas that arise within anorectal fistulas and those arising in the perianal area (anal margin). High-grade neuroendocrine carcinomas (small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma) are staged using this system. There is no AJCC staging system for anal mucosal melanomas and anal well-differentiated neuroendocrine tumors. (from AJCC 8th Ed.)
Stage IIA includes: T2, N0, M0. T2: Tumor larger than 2 cm but equal to or smaller than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T3, N0, M0. T3: Tumor larger than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIC includes: (T3, N1, M0); (T4, N1, M0). T3: Tumor larger than 5 cm. T4: Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder. N1: Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes. M0: No distant metastasis. (AJCC 8th ed.)
An antibody drug conjugate (ADC) composed of a monoclonal antibody that targets the tumor-associated antigen (TAA) AG7 and is linked, through a hydrophilic, self-immolative linker, to a proprietary cytotoxic payload, with potential antineoplastic activity. Upon administration of AbGn-107 the antibody moiety targets and binds to the AG7 antigen expressed on a variety of cancer cells. Upon binding and internalization, the linker is cleaved and the payload is released, binds to tubulin, inhibits tubulin polymerization and kills the AG7-expressing tumor cells.
An inhibitor of embryonic ectoderm development protein (EED) and allosteric inhibitor of polycomb repressive complex 2 (PRC2), with potential antineoplastic activity. Upon administration, MAK683 selectively binds to the domain of EED that interacts with trimethylated lysine 27 on histone 3 (H3K27me3), which leads to a conformational change in the EED H3K27me3-binding pocket and prevents the interaction of EED with the histone methyltransferase enhancer zeste homolog 2 (EZH2). Disruption of the EED-EZH2 protein-protein interaction (PPI) results in a loss of H3K27me3-stimulated PRC2 activity and prevents H3K27 trimethylation. This decrease in histone methylation alters gene expression patterns associated with cancer pathways and results in decreased tumor cell proliferation in EZH2-mutated and PRC2-dependent cancer cells. PRC2, a histone H3 lysine 27 methyltransferase and multi-protein complex comprised of EZH2, EED and suppressor of zeste 12 (SUZ12), plays a key role in gene regulation, especially during embryonic development. EZH2, the catalytic subunit of PRC2, is overexpressed or mutated in a variety of cancer cells. EED is essential for the histone methyltransferase activity of PRC2 because EED directly binds to H3K27me3.
An orally available inhibitor of multiple kinases, including the receptor tyrosine kinase anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), the neurotrophic tyrosine receptor kinase (NTRK) types 1, 2 and 3, the proto-oncogene SRC, and focal adhesion kinase (FAK), with potential antineoplastic activity. Upon oral administration, TPX-0005 binds to and inhibits wild-type, point mutants and fusion proteins of ALK, ROS1, NTRK1-3, SRC, FAK and, to a lesser extent, other kinases. Inhibition of these kinases leads to the disruption of downstream signaling pathways and the inhibition of cell growth of tumors in which these kinases are overexpressed, rearranged or mutated.
A radioimmunoconjugate composed of pertuzumab, a humanized recombinant monoclonal antibody directed against the extracellular dimerization domain of the tyrosine kinase receptor human epidermal growth factor-2 (HER2; HER-2), and linked, via the chelator desferrioxamine (DFO), to the radioisotope zirconium Zr 89 (Zr89), with potential use in imaging of HER-2-expressing tumor cells upon positron emission tomography (PET). Upon administration of zirconium Zr 89-DFO-pertuzumab, the pertuzumab moiety targets and binds to HER-2. After binding and internalization into HER-2-expressing tumor cells, Zr89 facilitates the visualization and detection of HER-2-expressing tumor cells using PET. This assesses HER2-expression and may predict or evaluate the tumor's response to certain HER-2-targeting chemotherapeutics.
A population of proprietary, off-the-shelf, three-dimensional (3D)-expanded, allogeneic placenta-derived stromal cells that can potentially be used to increase hematopoietic recovery from hematological disorders or after a hematopoietic stem cell transplant (HSCT). Upon intramuscular (IM) injection of placental expanded (PLX)-R18, these cells secrete a range of specific hematopoietic, regenerative proteins depending on their in vivo environment. The secreted proteins are involved in maintenance, renewal, proliferation, differentiation, and mobilization of hematopoietic progenitor cells (HPCs), and include, but are not limited to, granulocyte colony-stimulating factor (GCSF), monocyte chemoattractant protein-1 (MCP-1/CCL2), MCP-3 (CCL7), interleukin-6 (IL-6), and IL-8. This increases the number of colony-forming hematopoietic progenitors in the bone marrow, regenerates the bone marrow hematopoietic cells, and elevates and restores blood cell production.
A formulation containing the compound copper chloride (CuCl2), that can potentially be used to enhance Cu levels in cancer cells in order to elevate the antitumor activity of chemotherapeutic agents that are dependent on Cu for their activity. Upon intravenous administration of CuCl2, the mineral Cu is selectively taken up by and accumulates in cancer cells. In the presence of certain chemotherapeutic agents whose mechanism of action (MoA) is dependent on Cu, this formulation may enhance their cytotoxic activity.
A finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to carcinomas of the nonampullary duodenum, jejunum, and ileum. Only adenocarcinomas are assigned a stage group. Nonadenocarcinomas arising in the small intestine should have a TNM assigned but are not assigned a stage classification. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Small intestine cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Small intestine cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Small intestine cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Small intestine cancer with a finding of high grade dysplasia/carcinoma in situ. (from AJCC 8th Ed.)
Small intestine cancer with tumor invading the lamina propria or submucosa. (from AJCC 8th Ed.)
Small intestine cancer with tumor invading the lamina propria. (from AJCC 8th Ed.)
A carcinoma that arises from the gastrointestinal system and has metastasized to other anatomic sites.
Small intestine cancer with tumor invading the submucosa. (from AJCC 8th Ed.)
Small intestine cancer with tumor invading the muscularis propria. (from AJCC 8th Ed.)
Small intestine cancer with tumor invading through the muscularis propria into the subserosa, or extending into nonperitonealized perimuscular tissue (mesentery or retroperitoneum) without serosal penetration. For T3 tumors, the nonperitonealized perimuscular tissue is, for the jejunum and ileum, part of the mesentery and, for the duodenum in areas where serosa is lacking, part of the interface with the pancreas. (from AJCC 8th Ed.)
Small intestine cancer with tumor perforating the visceral peritoneum or directly invading other organs or structures (e.g., other loops of small intestine, mesentery of adjacent loops of bowel, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of small intestine cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Small intestine cancer in which the regional lymph node(s) cannot be assessed. (from AJCC 8th Ed.)
Small intestine cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Small intestine cancer with metastasis in three or more regional lymph nodes. (from AJCC 8th Ed.)
Any monoclonal antibody directed against te antigen fibroblast growth factor receptor (FGFR).
Uterine carcinoma that occurs in a rabbit.
A term that refers to the staging of small intestinal adenocarcinoma according to the American Joint Committee on Cancer, 8th edition. Nonadenocarcinomas arising in the small intestine should have a TNM assigned but are not assigned a stage classification. (from AJCC 8th Ed.)
Stage 0 includes: Tis, N0, M0. Tis: High grade dysplasia/carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1-2, N0, M0. T1: Tumor invading the lamina propria or submucosa. T2: Tumor invading the muscularis propria. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: T3, N0, M0; IIB: T4, N0, M0. T3: Tumor invading through the muscularis propria into the subserosa, or extending into nonperitonealized perimuscular tissue (mesentery or retroperitoneum) without serosal penetration. For T3 tumors, the nonperitonealized perimuscular tissue is, for the jejunum and ileum, part of the mesentery and, for the duodenum in areas where serosa is lacking, part of the interface with the pancreas. T4: Tumor perforating the visceral peritoneum or directly invading other organs or structures (e.g., other loops of small intestine, mesentery of adjacent loops of bowel, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor invading through the muscularis propria into the subserosa, or extending into nonperitonealized perimuscular tissue (mesentery or retroperitoneum) without serosal penetration. For T3 tumors, the nonperitonealized perimuscular tissue is, for the jejunum and ileum, part of the mesentery and, for the duodenum in areas where serosa is lacking, part of the interface with the pancreas. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T4, N0, M0. T4: Tumor perforating the visceral peritoneum or directly invading other organs or structures (e.g., other loops of small intestine, mesentery of adjacent loops of bowel, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: Any T, N1, M0; IIIB: Any T, N2, M0. N1: Metastasis in one or two regional lymph nodes. N2: Metastasis in three or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: Any T, N1, M0. N1: Metastasis in one or two regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: Any T, N2, M0. N2: Metastasis in three or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
A finding about one or more characteristics of appendiceal cancer, following the rules of the TNM AJCC v8 classification system. Carcinomas and well-differentiated neuroendocrine tumors (carcinoids) are separately categorized. (from AJCC 8th Ed.)
A finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v8 classification system. This staging system applies to carcinomas of the appendix, including high-grade neuroendocrine carcinomas, mixed adenoneuroendocrine carcinomas, and goblet cell carcinoids. Well-differentiated neuroendocrine tumors (carcinoids) are staged according to the classification for neuroendocrine tumors of the appendix. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Appendiceal carcinoma without evidence of distant metastasis. (from AJCC 8th Ed.)
Appendiceal carcinoma with distant metastasis. (from AJCC 8th Ed.)
Appendiceal carcinoma with intraperitoneal acellular mucin, without identifiable tumor cells in the disseminated peritoneal mucinous deposits. (from AJCC 8th Ed.)
Appendiceal carcinoma with intraperitoneal metastasis only, including peritoneal mucinous deposits containing tumor cells. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Appendiceal carcinoma with metastasis to sites other than peritoneum. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Appendiceal carcinoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Appendiceal carcinoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Appendiceal carcinoma with a finding of carcinoma in situ (intramucosal carcinoma; invasion of the lamina propria or extension into but not through the muscularis mucosae). (from AJCC 8th Ed.)
Low-grade appendiceal mucinous neoplasm confined by the muscularis propria. Acellular mucin or mucinous epithelium may invade into the muscularis propria. T1 and T2 are not applicable to LAMN. Acellular mucin or mucinous epithelium that extends into the subserosa or serosa should be classified as T3 or T4a, respectively. (from AJCC 8th Ed.)
Appendiceal carcinoma with tumor invading the submucosa (through the muscularis mucosa but not into the muscularis propria). (from AJCC 8th Ed.)
Appendiceal carcinoma with tumor invading the muscularis propria. (from AJCC 8th Ed.)
Appendiceal carcinoma with tumor invading through the muscularis propria into the subserosa or the mesoappendix. (from AJCC 8th Ed.)
Appendiceal carcinoma with tumor invading the visceral peritoneum, including the acellular mucin or mucinous epithelium involving the serosa of the appendix or mesoappendix, and/or directly invading adjacent organs or structures. (from AJCC 8th Ed.)
Appendiceal carcinoma with tumor invading through the visceral peritoneum, including the acellular mucin or mucinous epithelium involving the serosa of the appendix or serosa of the mesoappendix. (from AJCC 8th Ed.)
Appendiceal carcinoma with tumor directly invading or adhering to adjacent organs or structures. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of appendiceal carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Appendiceal carcinoma in which the regional lymph node(s) cannot be assessed. (from AJCC 8th Ed.)
Appendiceal carcinoma with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Appendiceal carcinoma in which one to three regional lymph nodes are positive (tumor in lymph node measuring 0.2 mm or more) or any number of tumor deposits is present, and all identifiable lymph nodes are negative. (from AJCC 8th Ed.)
Appendiceal carcinoma in which one regional lymph node is positive. (from AJCC 8th Ed.)
Appendiceal carcinoma in which two to three regional lymph nodes are positive. (from AJCC 8th Ed.)
Appendiceal carcinoma in which no regional lymph nodes are positive, but there are tumor deposits in the subserosa or mesentery. (from AJCC 8th Ed.)
Appendiceal carcinoma in which four or more regional lymph nodes are positive. (from AJCC 8th Ed.)
A term that refers to the staging of appendiceal carcinoma according to the American Joint Committee on Cancer, 8th edition. This staging system applies to carcinomas of the appendix, including high-grade neuroendocrine carcinomas, mixed adenoneuroendocrine carcinomas, and goblet cell carcinoids. Well-differentiated neuroendocrine tumors (carcinoids) are staged according to the classification for neuroendocrine tumors of the appendix. (from AJCC 8th Ed.)
Stage 0 includes: Tis(LAMN), N0, M0. Tis(LAMN): Low-grade appendiceal mucinous neoplasm confined by the muscularis propria. Acellular mucin or mucinous epithelium may invade into the muscularis propria. T1 and T2 are not applicable to LAMN. Acellular mucin or mucinous epithelium that extends into the subserosa or serosa should be classified as T3 or T4a, respectively. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T1, N1, M0); (T2, N1, M0); IIIB: (T3, N1, M0); (T4, N1, M0); IIIC: (Any T, N2, M0). T1: Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria). T2: Tumor invades the muscularis propria. T3: Tumor invades through the muscularis propria into the subserosa or the mesoappendix. T4: Tumor invades the visceral peritoneum, including the acellular mucin or mucinous epithelium involving the serosa of the appendix or mesoappendix, and/or directly invades adjacent organs or structures. N1: One to three regional lymph nodes are positive (tumor in lymph node measuring 0.2 mm or more) or any number of tumor deposits is present, and all identifiable lymph nodes are negative. N2: Four or more regional lymph nodes are positive. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (Any T, N0, M1a); (Any T, Any N, M1b, G1); IVB: (Any T, Any N, M1b, G2, G3, or GX); IVC: (Any T, Any N, M1c, Any G). N0: No regional lymph node metastasis. M1a: Intraperitoneal acellular mucin, without identifiable tumor cells in the disseminated peritoneal mucinous deposits. M1b: Intraperitoneal metastasis only, including peritoneal mucinous deposits containing tumor cells. M1c: Metastasis to sites other than peritoneum. G1: Well differentiated. G2: Moderately differentiated. G3: Poorly differentiated. GX: Grade cannot be assessed. (AJCC 8th ed.)
A finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v8 classification system. Adenocarcinomas, high-grade neuroendocrine carcinomas, and squamous cell carcinomas of the colon and rectum are covered by this staging system. Appendiceal carcinomas, anal carcinomas, and well-differentiated neuroendocrine tumors (carcinoids) are not covered by this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Colorectal cancer without evidence of distant metastasis by imaging, etc.; no evidence of tumor in distant sites or organs. This category is not assigned by pathologists. (from AJCC 8th Ed.)
Colorectal cancer with metastasis to one or more distant sites or organs or peritoneal metastasis is identified. (from AJCC 8th Ed.)
Colorectal cancer with metastasis to one site or organ without peritoneal metastasis. (from AJCC 8th Ed.)
Colorectal cancer with metastasis to two or more sites or organs without peritoneal metastasis. (from AJCC 8th Ed.)
Colorectal cancer with metastasis to the peritoneal surface alone or with other site or organ metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A neuroblastoma that does not respond to treatment.
A lymphoma that does not respond to treatment.
Colorectal cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
The reemergence of a lymphoma after a period of remission.
Colorectal cancer with a finding of carcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no extension through muscularis mucosae). (from AJCC 8th Ed.)
Colorectal cancer with tumor invading the submucosa (through the muscularis mucosa but not into the muscularis propria). (from AJCC 8th Ed.)
Colorectal cancer with tumor invading the muscularis propria. (from AJCC 8th Ed.)
Colorectal cancer with tumor invading through the muscularis propria into pericolorectal tissues. (from AJCC 8th Ed.)
Colorectal cancer with tumor invading the visceral peritoneum or invading or adhering to adjacent organ or structure. (from AJCC 8th Ed.)
Colorectal cancer with tumor invading through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum). (from AJCC 8th Ed.)
Colorectal cancer with tumor directly invading or adhering to adjacent organs or structures. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of colorectal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Colorectal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
A histiocytic and dendritic cell neoplasm that does not respond to treatment.
Colorectal cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Colorectal cancer in which one to three regional lymph nodes are positive (tumor in lymph nodes measuring 0.2 mm or more), or any number of tumor deposits are present and all identifiable lymph nodes are negative. (from AJCC 8th Ed.)
Colorectal cancer in which one regional lymph node is positive. (from AJCC 8th Ed.)
The reemergence of a histiocytic and dendritic cell neoplasm after a period of remission.
Colorectal cancer in which two or three regional lymph nodes are positive. (from AJCC 8th Ed.)
Colorectal cancer in which no regional lymph nodes are positive, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic, or perirectal/mesorectal tissues. (from AJCC 8th Ed.)
The reemergence of Langerhans cell histiocytosis after a period of remission.
Colorectal cancer in which four or more regional lymph nodes are positive. (from AJCC 8th Ed.)
Langerhans cell histiocytosis that does not respond to treatment.
Colorectal cancer in which four to six regional lymph nodes are positive. (from AJCC 8th Ed.)
Colorectal cancer in which seven or more regional lymph nodes are positive. (from AJCC 8th Ed.)
A term that refers to the staging of colorectal cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to adenocarcinomas, high-grade neuroendocrine carcinomas, and squamous cell carcinomas of the colon and rectum. Appendiceal carcinomas, anal carcinomas, and well-differentiated neuroendocrine tumors (carcinoids) are not covered by this staging system. (from AJCC 8th Ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ, intramucosal carcinoma (involvement of lamina propria with no extension through muscularis mucosae). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T3, N0, M0. T3: Tumor invades through the muscularis propria into pericolorectal tissues. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T4a, N0, M0. T4a: Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T1-T2, N1/N1c, M0); (T1, N2a, M0); IIIB: (T3-T4a, N1/N1c, M0); (T2-T3, N2a, M0); (T1-T2, N2b, M0); IIIC: (T4a, N2a, M0); (T3-T4a, N2b, M0); (T4b, N1-N2, M0). T1: Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria). T2: Tumor invades the muscularis propria. T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum). T4b: Tumor directly invades or adheres to adjacent organs or structures. N1: One to three regional lymph nodes are positive (tumor in lymph nodes measuring 0.2 mm or more), or any number of tumor deposits are present and all identifiable lymph nodes are negative. N1c: No regional lymph nodes are positive, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic, or perirectal/mesorectal tissues. N2: Four or more regional lymph nodes are positive. N2a: Four to six regional lymph nodes are positive. N2b: Seven or more regional lymph nodes are positive. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: (T1-T2, N1/N1c, M0); (T1, N2a, M0). T1: Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria). T2: Tumor invades the muscularis propria. N1: One to three regional lymph nodes are positive (tumor in lymph nodes measuring 0.2 mm or more), or any number of tumor deposits are present and all identifiable lymph nodes are negative. N1c: No regional lymph nodes are positive, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic, or perirectal/mesorectal tissues. N2a: Four to six regional lymph nodes are positive. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T3-T4a, N1/N1c, M0); (T2-T3, N2a, M0); (T1-T2, N2b, M0). T1: Tumor invades the submucosa (through the muscularis mucosa but not into the muscularis propria). T2: Tumor invades the muscularis propria. T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum). N1: One to three regional lymph nodes are positive (tumor in lymph nodes measuring 0.2 mm or more), or any number of tumor deposits are present and all identifiable lymph nodes are negative. N1c: No regional lymph nodes are positive, but there are tumor deposits in the subserosa, mesentery, or nonperitonealized pericolic, or perirectal/mesorectal tissues. N2a: Four to six regional lymph nodes are positive. N2b: Seven or more regional lymph nodes are positive. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIC includes: (T4a, N2a, M0); (T3-T4a, N2b, M0); (T4b, N1-N2, M0). T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum). T4b: Tumor directly invades or adheres to adjacent organs or structures. N1: One to three regional lymph nodes are positive (tumor in lymph nodes measuring 0.2 mm or more), or any number of tumor deposits are present and all identifiable lymph nodes are negative. N2: Four or more regional lymph nodes are positive. N2a: Four to six regional lymph nodes are positive. N2b: Seven or more regional lymph nodes are positive. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (Any T, Any N, M1a); IVB: (Any T, Any N, M1b); IVC: (Any T, Any N, M1c). M1a: Metastasis to one site or organ without peritoneal metastasis. M1b: Metastasis to two or more sites or organs without peritoneal metastasis. M1c: Metastasis to the peritoneal surface alone or with other site or organ metastases. (AJCC 8th ed.)
Stage IVA includes: Any T, Any N, M1a. M1a: Metastasis to one site or organ without peritoneal metastasis. (AJCC 8th ed.)
Stage IVB includes: Any T, Any N, M1b. M1b: Metastasis to two or more sites or organs without peritoneal metastasis. (AJCC 8th ed.)
Stage IVC includes: Any T, Any N, M1c. M1c: Metastasis to the peritoneal surface alone or with other site or organ metastases. (AJCC 8th ed.)
A term that refers to the staging of colon cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to adenocarcinomas, high-grade neuroendocrine carcinomas, and squamous cell carcinomas of the colon. (from AJCC 8th Ed.)
A term that refers to the staging of rectal cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to adenocarcinomas, high-grade neuroendocrine carcinomas, and squamous cell carcinomas of the rectum. (from AJCC 8th Ed.)
Stage II includes: IIA: T3, N0, M0; IIB: T4a, N0, M0; IIC: T4b, N0, M0. T3: Tumor invades through the muscularis propria into pericolorectal tissues. T4a: Tumor invades through the visceral peritoneum (including gross perforation of the bowel through tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral peritoneum). T4b: Tumor directly invades or adheres to adjacent organs or structures. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
A change in the amino acid residue at position 679 in the fibroblast growth factor receptor 2 protein where valine has been replaced by phenylalanine.
A finding about one or more characteristics of hepatobiliary system cancer, following the rules of the TNM AJCC v8 classification system. (from AJCC 8th Ed.)
A finding about one or more characteristics of hepatocellular carcinoma, following the rules of the TNM AJCC v8 classification system. This staging system applies to hepatocellular carcinomas and fibrolamellar carcinomas (fibrolamellar variant of hepatocellular carcinoma). Intrahepatic cholangiocarcinomas, combined hepatocellular-cholangiocarcinomas, and sarcomas of the liver are not staged using this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of hepatocellular carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of hepatocellular carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Hepatocellular carcinoma without evidence of distant metastasis. (from AJCC 8th Ed.)
Hepatocellular carcinoma with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of hepatocellular carcinoma, following the rules of the TNM AJCC v8 classification system.
A molecular genetic abnormality indicating the presence of an in-frame insertion mutation occurring within exon 19 of the EGFR gene.
A pathologic finding about one or more characteristics of hepatocellular carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A genetic finding indicating that codon 600 of the BRAF gene encodes the wild type amino acid, valine.
A pathologic finding about one or more characteristics of hepatocellular carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Hepatocellular carcinoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Hepatocellular carcinoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Hepatocellular carcinoma with solitary tumor equal to or less than 2 cm, or larger than 2 cm without vascular invasion. (from AJCC 8th Ed.)
Hepatocellular carcinoma with solitary tumor larger than 2 cm without vascular invasion. (from AJCC 8th Ed.)
Hepatocellular carcinoma with solitary tumor larger than 2 cm with vascular invasion, or multiple tumors, none larger than 5 cm. (from AJCC 8th Ed.)
Hepatocellular carcinoma with multiple tumors, at least one of which is larger than 5 cm. (from AJCC 8th Ed.)
Hepatocellular carcinoma with single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein, or tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of hepatocellular carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Hepatocellular carcinoma in which the regional lymph node(s) cannot be assessed. (from AJCC 8th Ed.)
Hepatocellular carcinoma with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Hepatocellular carcinoma with regional lymph node metastasis. (from AJCC 8th Ed.)
A variation in the amino acid sequence of the tyrosine-protein kinase BTK protein.
A change in the cysteine at position 600 of the tyrosine-protein kinase BTK protein to another amino acid.
A mutation in a RAF family gene that encodes a constitutively active serine/threonine-protein kinase and results in aberrant activation of its downstream pathways.
A change in the nucleotide sequence of the RAD51B gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the CDK12 gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the PPP2R2A gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the FANCL gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the CHEK2 gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the CHEK1 gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the ATM gene that is associated with increased risk of disease.
A term that refers to the staging of intrahepatic cholangiocarcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of hepatocellular carcinoma according to the American Joint Committee on Cancer, 8th edition. This staging system applies to hepatocellular carcinomas and fibrolamellar carcinomas (fibrolamellar variant of hepatocellular carcinoma). Intrahepatic cholangiocarcinomas, combined hepatocellular-cholangiocarcinomas, and sarcomas of the liver are not staged using this staging system. (from AJCC 8th Ed.)
Stage I includes: IA (T1a, N0, M0); IB (T1b, N0, M0). T1a: Solitary tumor equal to or less than 2 cm. T1b: Solitary tumor larger than 2 cm without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA includes: T1a, N0, M0. T1a: Solitary tumor equal to or less than 2 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IB includes: T1b, N0, M0. T1b: Solitary tumor larger than 2 cm without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T3, N0, M0); IIIB: (T4, N0, M0). T3: Multiple tumors, at least one of which is larger than 5 cm. T4: Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein, or tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: T3, N0, M0. T3: Multiple tumors, at least one of which is larger than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: T4, N0, M0. T4: Single tumor or multiple tumors of any size involving a major branch of the portal vein or hepatic vein, or tumor(s) with direct invasion of adjacent organs other than the gallbladder or with perforation of visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (Any T, N1, M0); IVB: (Any T, Any N, M1). N1: Regional lymph node metastasis. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: Any T, N1, M0. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
A condition that is relevant to either disease states or models of disease in cats.
A condition that is relevant to either disease states or models of disease in rabbits.
A neoplastic condition affecting experimental organisms based on the classification of the affected organism.
A condition that is relevant to either disease states or models of disease in chickens.
A condition that is relevant to either disease states or models of disease in horses.
A malignant lymphoma that arises in the bursa of Fabricius in a chicken.
Bronchioloalveolar lung carcinoma that occurs in a cat.
Adenocarcinoma that occurs in a guinea pig.
Buccal pouch carcinoma that occurs in a hamster.
Cholangiocarcinoma that occurs in a hamster.
Ductus deferens leiomyosarcoma that occurs in a hamster.
Uterine leiomyosarcoma that occurs in a hamster.
Basal Cell carcinoma that occurs in a mouse.
Hepatoma that occurs in Oryzias latipes.
Melanoma that occurs in Oryzias latipes.
Hepatoma that occurs in Oncorhynchus mykiss.
A neoplastic condition that is relevant to either disease states or models of disease in experimental organisms.
A finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to intrahepatic cholangiocarcinomas, combined hepatocellular-cholangiocarcinomas (mixed hepatocholangiocarcinomas), and primary neuroendocrine tumors of the liver. Primary sarcomas of the liver, pure hepatocellular carcinomas, hilar cholangiocarcinomas, and gallbladder carcinomas are not staged using this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Intrahepatic bile duct cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Intrahepatic bile duct cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with a finding of carcinoma in situ (intraductal tumor). (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with solitary tumor equal to or less than 5 cm, or larger than 5 cm without vascular invasion. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with solitary tumor equal to or less than 5 cm without vascular invasion. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with solitary tumor larger than 5 cm without vascular invasion. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with solitary tumor with intrahepatic vascular invasion, or multiple tumors, with or without vascular invasion. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with tumor perforating the visceral peritoneum. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with tumor involving local extrahepatic structures by direct invasion. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of intrahepatic bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Intrahepatic bile duct cancer in which the regional lymph node(s) cannot be assessed. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Intrahepatic bile duct cancer with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of intrahepatic bile duct cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to intrahepatic cholangiocarcinomas, combined hepatocellular-cholangiocarcinomas (mixed hepatocholangiocarcinomas), and primary neuroendocrine tumors of the liver. Primary sarcomas of the liver, pure hepatocellular carcinomas, hilar cholangiocarcinomas, and gallbladder carcinomas are not staged using this staging system. (from AJCC 8th Ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ (intraductal tumor). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: IA (T1a, N0, M0); IB (T1b, N0, M0). T1a: Solitary tumor equal to or less than 5 cm without vascular invasion. T1b: Solitary tumor larger than 5 cm without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA includes: T1a, N0, M0. T1a: Solitary tumor equal to or less than 5 cm without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IB includes: T1b, N0, M0. T1b: Solitary tumor larger than 5 cm without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Solitary tumor with intrahepatic vascular invasion, or multiple tumors, with or without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T3, N0, M0); IIIB: (T4, N0, M0); (Any T, N1, M0). T3: Tumor perforating the visceral peritoneum. T4: Tumor involving local extrahepatic structures by direct invasion. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: T3, N0, M0. T3: Tumor perforating the visceral peritoneum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T4, N0, M0); (Any T, N1, M0). T4: Tumor involving local extrahepatic structures by direct invasion. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
A preparation of allogeneic platelets that have been treated with Mirasol, a proprietary pathogen reduction technology (PRT) system, and can potentially be used to improve symptoms associated with thrombocytopenia. Upon apheresis, platelets are treated with the patented PRT system, which includes treatment of the platelets with riboflavin (vitamin B2) and broad-spectrum ultraviolet (UV) light. The treatment causes irreversible changes to the RNA and DNA of a broad range of pathogens, including viruses, bacteria, parasites and white blood cells (WBCs), which prevents them from replicating and causing disease. After ex vivo treatment and upon transfusion, the Mirasol-treated allogeneic platelets may reduce thrombocytopenia and prevent bleeding. By preventing the replication of contaminating pathogens, Mirasol treatment improves transfusion safety. Inactivation of WBCs may reduce transfusion reactions and immunological complications in patients.
A finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to gallbladder carcinomas. Well-differentiated neuroendocrine tumors and sarcomas are not staged using this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Gallbladder cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Gallbladder cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Gallbladder cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Gallbladder cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Gallbladder cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Gallbladder cancer with tumor invading the lamina propria or muscular layer. (from AJCC 8th Ed.)
Gallbladder cancer with tumor invading the lamina propria. (from AJCC 8th Ed.)
Gallbladder cancer with tumor invading the muscular layer. (from AJCC 8th Ed.)
Gallbladder cancer with tumor invading the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum); or tumor invading the perimuscular connective tissue on the hepatic side, with no extension into the liver. (from AJCC 8th Ed.)
Gallbladder cancer with tumor invading the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). (from AJCC 8th Ed.)
Gallbladder cancer with tumor invading the perimuscular connective tissue on the hepatic side, with no extension into the liver. (from AJCC 8th Ed.)
Gallbladder cancer with tumor perforating the serosa (visceral peritoneum) and/or directly invading the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. (from AJCC 8th Ed.)
Gallbladder cancer with tumor invading the main portal vein or hepatic artery or invading two or more extrahepatic organs or structures. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of gallbladder cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Gallbladder cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Gallbladder cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Gallbladder cancer with metastases to one to three regional lymph nodes. (from AJCC 8th Ed.)
Gallbladder cancer with metastases to four or more regional lymph nodes. (from AJCC 8th Ed.)
A term that refers to the staging of gallbladder cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to gallbladder carcinomas. Well-differentiated neuroendocrine tumors and sarcomas are not staged using this staging system. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor invading the lamina propria or muscular layer. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: T2a, N0, M0; IIB: T2b, N0, M0. T2a: Tumor invading the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). T2b: Tumor invading the perimuscular connective tissue on the hepatic side, with no extension into the liver. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T2a, N0, M0. T2a: Tumor invading the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T2b, N0, M0. T2b: Tumor invading the perimuscular connective tissue on the hepatic side, with no extension into the liver. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T3, N0, M0); IIIB: (T1-3, N1, M0). T1: Tumor invading the lamina propria or muscular layer. T2: Tumor invading the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum); or tumor invading the perimuscular connective tissue on the hepatic side, with no extension into the liver. T3: Tumor perforating the serosa (visceral peritoneum) and/or directly invading the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. N0: No regional lymph node metastasis. N1: Metastases to one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: T3, N0, M0. T3: Tumor perforating the serosa (visceral peritoneum) and/or directly invading the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: T1-3, N1, M0. T1: Tumor invading the lamina propria or muscular layer. T2: Tumor invading the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum); or tumor invading the perimuscular connective tissue on the hepatic side, with no extension into the liver. T3: Tumor perforating the serosa (visceral peritoneum) and/or directly invading the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. N1: Metastases to one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: T4, N0-1, M0; IVB: (Any T, N2, M0); (Any T, Any N, M1). T4: Tumor invading the main portal vein or hepatic artery or invading two or more extrahepatic organs or structures. N0: No regional lymph node metastasis. N1: Metastases to one to three regional lymph nodes. N2: Metastases to four or more regional lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: T4, N0-1, M0. T4: Tumor invading the main portal vein or hepatic artery or invading two or more extrahepatic organs or structures. N0: No regional lymph node metastasis. N1: Metastases to one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: (Any T, N2, M0); (Any T, Any N, M1). N2: Metastases to four or more regional lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
A finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to perihilar cholangiocarcinomas. Well-differentiated neuroendocrine tumors and sarcomas are not staged using this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Perihilar bile duct cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Perihilar bile duct cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Perihilar bile duct cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Perihilar bile duct cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Perihilar bile duct cancer with a finding of carcinoma in situ/high grade dysplasia. (from AJCC 8th Ed.)
Perihilar bile duct cancer with tumor confined to the bile duct, with extension up to the muscle layer or fibrous tissue. (from AJCC 8th Ed.)
Perihilar bile duct cancer with tumor invading beyond the wall of the bile duct to surrounding adipose tissue, or tumor invading adjacent hepatic parenchyma. (from AJCC 8th Ed.)
Perihilar bile duct cancer with tumor invading beyond the wall of the bile duct to surrounding adipose tissue. (from AJCC 8th Ed.)
Perihilar bile duct cancer with tumor invading adjacent hepatic parenchyma. (from AJCC 8th Ed.)
Perihilar bile duct cancer with tumor invading unilateral branches of the portal vein or hepatic artery. (from AJCC 8th Ed.)
Perihilar bile duct cancer with tumor invading the main portal vein or its branches bilaterally, or the common hepatic artery; or unilateral second-order biliary radicals with contralateral portal vein or hepatic artery involvement. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Perihilar bile duct cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Perihilar bile duct cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Perihilar bile duct cancer with one to three positive lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. (from AJCC 8th Ed.)
Perihilar bile duct cancer with four or more positive lymph nodes involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. (from AJCC 8th Ed.)
A term that refers to the staging of hilar cholangiocarcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of hilar cholangiocarcinoma according to the American Joint Committee on Cancer, 8th edition. Hilar well-differentiated neuroendocrine tumors and sarcomas are not staged using this staging system. (from AJCC 8th Ed.)
Stage III includes: IIIA: (T3, N0, M0); IIIB: (T4, N0, M0); IIIC: (Any T, N1, M0). T3: Tumor invading unilateral branches of the portal vein or hepatic artery. T4: Tumor invading the main portal vein or its branches bilaterally, or the common hepatic artery; or unilateral second-order biliary radicals with contralateral portal vein or hepatic artery involvement. N0: No regional lymph node metastasis. N1: One to three positive lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIC includes: Any T, N1, M0. N1: One to three positive lymph nodes typically involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (Any T, N2, M0); IVB: (Any T, Any N, M1). N2: Four or more positive lymph nodes involving the hilar, cystic duct, common bile duct, hepatic artery, posterior pancreatoduodenal, and portal vein lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
A term that refers to the staging of intrahepatic cholangiocarcinoma according to the American Joint Committee on Cancer, 8th edition.
Stage I includes: IA (T1a, N0, M0); IB (T1b, N0, M0). T1a: Solitary tumor equal or less than 5 cm without vascular invasion. T1b: Solitary tumor larger than 5 cm without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA includes: T1a, N0, M0. T1a: Solitary tumor equal or less than 5 cm without vascular invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
A myxoma that occurs in the rectum of a cow.
A kidney neoplasm of the pronephric cell type that occurs in a frog.
A kidney neoplasm that occurs in a hamster.
Carcinoma that occurs in the rectum of a mouse.
Reticulum cell sarcoma that occurs in a mouse.
A neoplasm that occurs in the sinus of a sheep.
Lymphoma that occurs in a rhesus monkey.
A mammary neoplasm that occurs in a rhesus monkey.
A neoplasm that occurs in a zebra finch.
A finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to bile duct adenocarcinomas, biliary intraepithelial neoplasia, high-grade neuroendocrine carcinomas, and papillary carcinomas. Tumors arising in the ampulla of Vater, sarcomas, and well-differentiated neuroendocrine tumors (carcinoids) are not staged using this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Distal bile duct cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Distal bile duct cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Distal bile duct cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Distal bile duct cancer with a finding of carcinoma in situ/high-grade dysplasia. (from AJCC 8th Ed.)
Distal bile duct cancer with tumor invading the bile duct wall with a depth less than 5 mm. (from AJCC 8th Ed.)
Distal bile duct cancer with tumor invading the bile duct wall with a depth of 5-12 mm. (from AJCC 8th Ed.)
Distal bile duct cancer with tumor invading the bile duct wall with a depth greater than 12 mm. (from AJCC 8th Ed.)
Distal bile duct cancer with tumor involving the celiac axis, superior mesenteric artery, and/or common hepatic artery. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Distal bile duct cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Distal bile duct cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Distal bile duct cancer with metastasis in one to three regional lymph nodes. (from AJCC 8th Ed.)
Distal bile duct cancer with metastasis in four or more regional lymph nodes. (from AJCC 8th Ed.)
A term that refers to the staging of distal bile duct cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of distal bile duct cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to bile duct adenocarcinomas, biliary intraepithelial neoplasia, high-grade neuroendocrine carcinomas, and papillary carcinomas. Tumors arising in the ampulla of Vater, sarcomas, and well-differentiated neuroendocrine tumors (carcinoids) are not staged using this staging system. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor invading the bile duct wall with a depth less than 5 mm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: (T1, N1, M0); (T2, N0, M0); IIB: (T2, N1, M0); (T3, N0, M0); (T3, N1, M0). T1: Tumor invading the bile duct wall with a depth less than 5 mm. T2: Tumor invading the bile duct wall with a depth of 5-12 mm. T3: Tumor invading the bile duct wall with a depth greater than 12 mm. N0: No regional lymph node metastasis. N1: Metastasis in one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: (T1, N2, M0); (T2, N2, M0); (T3, N2, M0). T1: Tumor invading the bile duct wall with a depth less than 5 mm. T2: Tumor invading the bile duct wall with a depth of 5-12 mm. T3: Tumor invading the bile duct wall with a depth greater than 12 mm. N2: Metastasis in four or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0). T4: Tumor involving the celiac axis, superior mesenteric artery, and/or common hepatic artery. N0: No regional lymph node metastasis. N1: Metastasis in one to three regional lymph nodes. N2: Metastasis in four or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
A sebaceous gland carcinoma affecting the eyelid. It arises from the meibomian glands, glands of Zeis, or glands associated with the caruncle. It usually affects elderly women and is characterized by high rate of local recurrence, regional, and distant metastases.
The reemergence of Ph-like acute lymphoblastic leukemia after a period of remission.
Ph-like acute lymphoblastic leukemia that does not respond to treatment.
A finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v8 classification system. This staging system and classification does not apply to well-differentiated neuroendocrine (carcinoid) tumors but does apply to high-grade neuroendocrine carcinomas, such as small cell carcinoma and large cell neuroendocrine carcinoma. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Ampulla of Vater cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Ampulla of Vater cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Ampulla of Vater cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Ampulla of Vater cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Ampulla of Vater cancer with tumor limited to ampulla of Vater or sphincter of Oddi or tumor invading beyond the sphincter of Oddi (perisphincteric invasion) and/or into the duodenal submucosa. (from AJCC 8th Ed.)
Ampulla of Vater cancer with tumor limited to ampulla of Vater or sphincter of Oddi. (from AJCC 8th Ed.)
Ampulla of Vater cancer with tumor invading beyond the sphincter of Oddi (perisphincteric invasion) and/or into the duodenal submucosa. (from AJCC 8th Ed.)
Ampulla of Vater cancer with tumor invading into the muscularis propria of the duodenum. (from AJCC 8th Ed.)
Ampulla of Vater cancer with tumor directly invading the pancreas (up to 0.5 cm) or tumor extending more than 0.5 cm into the pancreas, or extending into peripancreatic or periduodenal tissue or duodenal serosa without involvement of the celiac axis or superior mesenteric artery. (from AJCC 8th Ed.)
Ampulla of Vater cancer with tumor directly invading the pancreas (up to 0.5 cm). (from AJCC 8th Ed.)
Ampulla of Vater cancer with tumor extending more than 0.5 cm into the pancreas, or extending into peripancreatic tissue or duodenal serosa without involvement of the celiac axis or superior mesenteric artery. (from AJCC 8th Ed.)
Ampulla of Vater cancer with tumor involving the celiac axis, superior mesenteric artery, and/or common hepatic artery, irrespective of size. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of ampulla of Vater cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Ampulla of Vater cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Ampulla of Vater cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Ampulla of Vater cancer with metastasis to one to three regional lymph nodes. (from AJCC 8th Ed.)
Ampulla of Vater cancer with metastasis to four or more regional lymph nodes. (from AJCC 8th Ed.)
A term that refers to the staging of ampulla of Vater cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of ampulla of Vater cancer according to the American Joint Committee on Cancer, 8th edition. This staging system does not apply to well-differentiated neuroendocrine (carcinoid) tumors but does apply to high-grade neuroendocrine carcinomas, such as small cell carcinoma and large cell neuroendocrine carcinoma. (from AJCC 8th Ed.)
Stage IIIA includes: (T1a, N1, M0); (T1b, N1, M0); (T2, N1, M0); (T3a, N1, M0); (T3b, N1, M0). T1a: Tumor limited to ampulla of Vater or sphincter of Oddi. T1b: Tumor invading beyond the sphincter of Oddi (perisphincteric invasion) and/or into the duodenal submucosa. T2: Tumor invading into the muscularis propria of the duodenum. T3a: Tumor directly invading the pancreas (up to 0.5 cm). T3b: Tumor extending more than 0.5 cm into the pancreas, or extending into peripancreatic tissue or duodenal serosa without involvement of the celiac axis or superior mesenteric artery. N1: Metastasis to one to three regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T4, Any N, M0); (Any T, N2, M0). T4: Tumor involving the celiac axis, superior mesenteric artery, and/or common hepatic artery, irrespective of size. N2: Metastasis to four or more regional lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
A finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v8 classification system. This classification applies to pancreatic ductal adenocarcinoma, acinar cell carcinoma, intraductal papillary mucinous neoplasm with associated invasive carcinoma, intraductal tubulopapillary neoplasm with associated invasive carcinoma, colloid carcinoma, mucinous cystic neoplasm with associated invasive carcinoma, solid pseudopapillary neoplasm, large cell neuroendocrine carcinoma, small cell neuroendocrine carcinoma, and pancreatoblastoma. Well-differentiated neuroendocrine tumors are not staged using this staging system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Exocrine pancreatic cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Exocrine pancreatic cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with a finding of carcinoma in situ. This includes high-grade pancreatic intraepithelial neoplasia (PanIn-3), intraductal papillary mucinous neoplasm with high-grade dysplasia, intraductal tubulopapillary neoplasm with high-grade dysplasia, and mucinous cystic neoplasm with high-grade dysplasia. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with tumor measuring 2 cm or less in greatest dimension. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with tumor measuring 0.5 cm or less in greatest dimension. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with tumor measuring more than 0.5 cm and less than 1 cm in greatest dimension. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with tumor measuring 1-2 cm in greatest dimension. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with tumor measuring more than 2 cm and 4 cm or less in greatest dimension. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with tumor measuring more than 4 cm in greatest dimension. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with tumor involving the celiac axis, superior mesenteric artery, and/or common hepatic artery, regardless of size. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of exocrine pancreatic cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Exocrine pancreatic cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with metastasis in one to three regional lymph nodes. (from AJCC 8th Ed.)
Exocrine pancreatic cancer with metastasis in four or more regional lymph nodes. (from AJCC 8th Ed.)
A cytogenetic abnormality that refers to any translocation involving the BCL6 gene.
A term that refers to the staging of exocrine and endocrine pancreatic cancer including well-differentiated neuroendocrine tumors according to the American Joint Committee on Cancer, 6th and 7th editions.
A term that refers to the staging of exocrine pancreatic cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to pancreatic ductal adenocarcinoma, acinar cell carcinoma, intraductal papillary mucinous neoplasm with associated invasive carcinoma, intraductal tubulopapillary neoplasm with associated invasive carcinoma, colloid carcinoma, mucinous cystic neoplasm with associated invasive carcinoma, solid pseudopapillary neoplasm, large cell neuroendocrine carcinoma, small cell neuroendocrine carcinoma, and pancreatoblastoma. Well-differentiated neuroendocrine tumors are not staged using this staging system. (from AJCC 8th Ed.)
Fibrosarcoma that occurs in a budgerigar.
Pancreatic carcinoma that occurs in a dog.
Monocytic leukemia that occurs in a chicken.
A Leydig cell tumor that occurs in a mouse.
A mammary tumor that occurs in Suncus murinus.
A tumor arising from odontogenic epithelium and occurs in a dog.
A chondrosarcoma that occurs in a hamster.
A neoplasm that arises from vascular endothelium and occurs in the thyroid gland of a mouse.
A pheochromocytoma that occurs in the adrenal gland of a mouse.
A tumor arising in the submandibular gland of a mouse.
Hepatocellular carcinoma that occurs in Poeciliopsis lucida.
A selective inhibitor of mutated forms of B-RAF kinase at amino acid position 600 (BRAFV600), including BRAFV600E, the alpha, delta and, to a lesser extent, beta isoforms of phosphatidylinositide 3-kinase (PI3K), including mutated forms of PI3KCA, which encodes the p110-alpha catalytic subunit of the class I PI3K, and the phosphatase and tensin homologs (PTEN) with loss-of-function mutation, with potential antineoplastic activity. Upon administration of ASN003, this agent selectively targets, binds to and inhibits the activity of BRAFV600 mutants as well as mutated isoforms of PI3K. This inhibits signaling through B-RAF- and PI3K/mechanistic target of rapamycin (mTOR)-mediated pathways and inhibits cellular proliferation in tumor cells with BRAFV600 mutations, those expressing PI3K and/or those driven by PTEN. Dysregulation of the B-RAF- and PI3K-mediated pathways is frequently seen in a variety of tumors and results in increased tumor cell growth and survival. Dual targeting of both pathways may increase efficacy and anti-tumor potential compared to the targeting of just one pathway by a selective B-RAF inhibitor or selective PI3K pathway inhibitor alone.
A stage finding of AIDS-related Kaposi sarcoma according to the AIDS Clinical Trials Group system. The latter incorporates the extent of tumor (T), the status of the immune system (I), as measured by the number of CD4 cells present in the blood, and the extent of involvement within the body or systemic illness (S). Under each major heading, there are 2 subgroups: either a 0 (good risk) or a 1 (poor risk) group. (American Cancer Society)
A term that refers to the tumor status of AIDS-related Kaposi sarcoma according to the AIDS Clinical Trials Group system. (American Cancer Society)
AIDS-related Kaposi sarcoma is only in the skin and/or the lymph nodes, and/or there is only a small amount of disease on the palate. The Kaposi sarcoma lesions in the mouth are flat rather than raised. (American Cancer Society)
AIDS-related Kaposi sarcoma with widespread lesions.
AIDS-related Kaposi sarcoma with edema or ulceration due to the tumor.
AIDS-related Kaposi sarcoma with lesions that are nodular and/or lesions in roof of the mouth.
AIDS-related Kaposi sarcoma involving the esophagus, stomach, or intestines.
AIDS-related Kaposi sarcoma involving the lungs.
AIDS-related Kaposi sarcoma involving organs other than the lungs or gastrointestinal tract. It includes liver, bladder, reproductive tract, heart, and endocrine organs.
A term that refers to the immune system status of AIDS-related Kaposi sarcoma according to the AIDS Clinical Trials Group system. The immune status is assessed using the CD4 count test. (American Cancer Society)
AIDS-related Kaposi sarcoma in which the CD4 cell count is 150 or more cells per cubic mm.
AIDS-related Kaposi sarcoma in which the CD4 cell count is lower than 150 cells per cubic mm.
A term that refers to the systemic illness status of AIDS-related Kaposi sarcoma according to the AIDS Clinical Trials Group system. (American Cancer Society)
AIDS-related Kaposi sarcoma in which no systemic illness is present; there is no history of opportunistic infections or thrush and no B symptoms lasting more than 2 weeks. The Karnofsky performance status score is 70 or higher. (American Cancer Society)
AIDS-related Kaposi sarcoma in which systemic illness is present; one or more of the following is true: history of opportunistic infections or thrush; one or more B symptoms is present; Karnofsky performance status score is under 70; other HIV-related illness is present, such as neurological disease or lymphoma. (American Cancer Society)
The overall risk group for AIDS-related Kaposi sarcoma based on the tumor, immune system, and systemic illness status. Since highly active antiretroviral therapy became available to treat HIV, the immune system status has become less important and is often not counted in determining the risk group. (American Cancer Society)
The following combinations of tumor and systemic illness status define good risk AIDS-related Kaposi sarcoma: T0 S0, T1 S0, or T0 S1. T0: Localized tumor. T1: Widespread tumor. S0: No systemic illness is present. S1: Systemic illness is present. (American Cancer Society)
The following combination of tumor and systemic illness status define poor risk AIDS-related Kaposi sarcoma: T1 S1. T1: Widespread tumor. S1: Systemic illness is present. (American Cancer Society)
An orally bioavailable selective inhibitor of wild-type, mutant and fusion products involving the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET), with potential antineoplastic activity. Upon oral administration, LOXO-292 selectively binds to and targets various RET mutants and RET-containing fusion products. This results in an inhibition of cell growth of tumors cells that exhibit increased RET activity. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types; dysregulation of RET activity plays a key role in the development and progression of these cancers.
Carcinoma arising from the adrenal gland and occurring in a hamster.
Carcinoma arising from the lung and occurring in a hamster.
Carcinoma arising in the pituitary gland and occurring in a hamster.
A neoplasm that occurs in the small intestine of a hamster.
A fibroblastic tumor that occurs in the skin of a horse.
A lymphoma that arises in the thymus of a mouse.
Sarcoma arising from the connective tissue of the dermis and occurring in a walleye.
Carcinoma that arises in the testicle of a budgerigar.
Reticulum cell sarcoma that occurs in a cat.
A change in the nucleotide sequence of the PHOX2B gene.
A proprietary, personalized autologous synthetic cancer vaccine composed of patient-specific synthetic cancer neo-epitopes complexed with heat shock protein 70 (HSP 70; HSP70), with potential immunostimulating and antineoplastic activities. Upon administration of the autologous neoantigen-HSP70 cancer vaccine, the HSPs present the neoantigens to antigen presenting cells (APCs) and help elicit a potent neoantigen-specific T-cell-based anti-tumor immune response, thereby killing the neoantigen-expressing cancer cells. HSP70 is able to the transport the neo-epitopes, activate APCs and enhance the T-cell-mediated immune response.
A finding about one or more characteristics of a digestive system neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of a gastric neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to gastric ""carcinoid"" tumors (NET G1 and G2, and rare well-differentiated G3). Gastric high-grade neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma are not included in this classification system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of a gastric neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of a gastric neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Gastric neuroendocrine tumor without evidence of distant metastasis. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor with distant metastasis. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor with metastasis confined to liver. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor with metastasis in at least one extrahepatic site (e.g., lung, ovary, nonregional lymph node, peritoneum, bone). (from AJCC 8th Ed.)
Gastric neuroendocrine tumor with both hepatic and extrahepatic metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a gastric neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of a gastric neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of a gastric neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Gastric neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor with no evidence of primary tumor. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor invading the lamina propria or submucosa and is less than or equal to 1 cm in size. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor invading the muscularis propria or is greater than 1 cm in size. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor invading visceral peritoneum (serosa) or other organs or adjacent structures. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a gastric neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Gastric neuroendocrine tumor in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor with no metastasis to regional lymph nodes. (from AJCC 8th Ed.)
Gastric neuroendocrine tumor with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of a gastric neuroendocrine tumor according to the American Joint Committee on Cancer, 8th edition. This staging system applies to gastric ""carcinoid"" tumors (NET G1 and G2, and rare well-differentiated G3). Gastric high-grade neuroendocrine carcinoma and gastric mixed adenoneuroendocrine carcinoma are not included in this staging system. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor invading the lamina propria or submucosa and is less than or equal to 1 cm in size. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T2, N0, M0); (T3, N0, M0). T2: Tumor invading the muscularis propria or is greater than 1 cm in size. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0); (T4, N0, M0); (T4, N1, M0). T1: Tumor invading the lamina propria or submucosa and is less than or equal to 1 cm in size. T2: Tumor invading the muscularis propria or is greater than 1 cm in size. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. T4: Tumor invading visceral peritoneum (serosa) or other organs or adjacent structures. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: (T1, N0, N1, M1); (T2, N0, N1, M1); (T3, N0, N1, M1); (T4, N0, N1, M1). T1: Tumor invading the lamina propria or submucosa and is less than or equal to 1 cm in size. T2: Tumor invading the muscularis propria or is greater than 1 cm in size. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. T4: Tumor invading visceral peritoneum (serosa) or other organs or adjacent structures. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M1: Distant metastasis. (AJCC 8th ed.)
A finding about one or more characteristics of a duodenum and ampulla of Vater neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to well-differentiated neuroendocrine tumors of the duodenum and ampulla of Vater. Carcinomas of the duodenum, including high-grade (grade 3), poorly differentiated neuroendocrine carcinomas and carcinomas of the ampulla of Vater, including high-grade (grade 3), poorly differentiated neuroendocrine carcinomas are not included in this classification system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of a duodenum and ampulla of Vater neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of a duodenum and ampulla of Vater neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Duodenum and ampulla of Vater neuroendocrine tumor without evidence of distant metastasis. (from AJCC 8th Ed.)
Duodenum and ampulla of Vater neuroendocrine tumor with distant metastasis. (from AJCC 8th Ed.)
Duodenum and ampulla of Vater neuroendocrine tumor with metastasis confined to liver. (from AJCC 8th Ed.)
Duodenum and ampulla of Vater neuroendocrine tumor with metastasis in at least one extrahepatic site (e.g., lung, ovary, nonregional lymph node, peritoneum, bone). (from AJCC 8th Ed.)
Duodenum and ampulla of Vater neuroendocrine tumor with both hepatic and extrahepatic metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a duodenum and ampulla of Vater neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of a duodenum and ampulla of Vater neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of a duodenum and ampulla of Vater neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Duodenum and ampulla of Vater neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Duodenum neuroendocrine tumor invading the mucosa or submucosa only and is equal or less than 1 cm; Ampulla of Vater neuroendocrine tumor measuring 1 cm or less and is confined within the sphincter of Oddi. (from AJCC 8th Ed.)
Duodenum neuroendocrine tumor invading the muscularis propria or measuring more than 1 cm; Ampulla of Vater neuroendocrine tumor invading through the sphincter of Oddi into duodenal submucosa or muscularis propria, or measuring more than 1 cm. (from AJCC 8th Ed.)
Duodenum and ampulla of Vater neuroendocrine tumor invading the pancreas or peripancreatic adipose tissue. (from AJCC 8th Ed.)
Duodenum and ampulla of Vater neuroendocrine tumor invading the visceral peritoneum (serosa) or other organs. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a duodenum and ampulla of Vater neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Duodenum and ampulla of Vater neuroendocrine tumor in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Duodenum and ampulla of Vater neuroendocrine tumor without regional lymph node involvement. (from AJCC 8th Ed.)
Duodenum and ampulla of Vater neuroendocrine tumor with regional lymph node involvement. (from AJCC 8th Ed.)
A term that refers to the staging of a duodenal neuroendocrine tumor according to the American Joint Committee on Cancer, 8th edition. This staging system applies to well-differentiated neuroendocrine tumors of the duodenum. Carcinomas of the duodenum, including high-grade (grade 3), poorly differentiated neuroendocrine carcinomas are not included in this staging system. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor invading the mucosa or submucosa only and is equal or less than 1 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T2, N0, M0); (T3, N0, M0). T2: Tumor invading the muscularis propria or measuring more than 1 cm. T3: Tumor invading the pancreas or peripancreatic adipose tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T4, N0, M0); (Any T, N1, M0). T4: Tumor invading the visceral peritoneum (serosa) or other organs. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the duodenum.
A term that refers to the staging of an ampulla of Vater neuroendocrine tumor according to the American Joint Committee on Cancer, 8th edition. This staging system applies to well-differentiated neuroendocrine tumors of the ampulla of Vater. Carcinomas of the ampulla of Vater, including high-grade (grade 3), poorly differentiated neuroendocrine carcinomas are not included in this staging system. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor measuring 1 cm or less and is confined within the sphincter of Oddi. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T2, N0, M0); (T3, N0, M0). T2: Tumor invading through the sphincter of Oddi into duodenal submucosa or muscularis propria, or measuring more than 1 cm. T3: Tumor invading the pancreas or peripancreatic adipose tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the jejunum.
A solution consisting of a combination of two toll-like receptor (TLR) ligands: Pam2CSK4 acetate (Pam2), a synthetic diacylated lipopeptide (LP) that is an agonist of TLR2 and TLR6 (TLR2/6) and the TLR9 agonist oligodeoxynucleotide (ODN) M362, which contains unmethylated CpG-based dinucleotides, with potential immunostimulating activity. Upon administration via inhalation of the PUL-042 solution, the components in PUL-042 bind to and activate TLRs on lung epithelial cells. This induces the epithelial cells to produce peptides and reactive oxygen species (ROS) against pathogens, including bacteria, fungi and viruses, that are present in the lungs. M362, through binding of the CpG motifs to TLR9 and subsequent TLR9-mediated signaling, initiates the innate immune system and activates macrophages, natural killer (NK) cells, B-cells, and plasmacytoid dendritic cells (pDCs), stimulates interferon-alpha (IFN-a) production and induces a T-helper 1 cells (Th1)-mediated immune response. Pam2CSK4, through TLR2/6, activates the production of T-helper 2 cells (Th2), leading to the production of Th2-specific cytokines. Altogether, this protects against and kills the pathogens present in the lungs and prevents pulmonary infection. TLRs play fundamental roles in both pathogen recognition and the activation of innate immunity.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the ileum.
A finding about one or more characteristics of a jejunum and ileum neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to small bowel ""carcinoid"" tumors (NET G1 and G2, and rare well-differentiated G3) arising in the jejunum and ileum. This classification system does not apply to high-grade neuroendocrine carcinomas, mixed adenoneuroendocrine carcinomas, and neuroendocrine tumors of the duodenum. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of a jejunum and ileum neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of a jejunum and ileum neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Jejunum and ileum neuroendocrine tumor without evidence of distant metastasis. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor with distant metastasis. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor with metastasis confined to liver. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor with metastasis in at least one extrahepatic site (e.g., lung, ovary, nonregional lymph node, peritoneum, bone). (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor with both hepatic and extrahepatic metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a jejunum and ileum neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of a jejunum and ileum neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of a jejunum and ileum neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Jejunum and ileum neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor with no evidence of primary tumor. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor invading lamina propria or submucosa and measuring 1 cm or less in size. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor invading muscularis propria or measuring more than 1 cm in size. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor invading visceral peritoneum (serosa) or other organs or adjacent structures. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a jejunum and ileum neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Jejunum and ileum neuroendocrine tumor in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor without regional lymph node metastasis. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor with regional lymph node metastasis in less than 12 nodes. (from AJCC 8th Ed.)
Jejunum and ileum neuroendocrine tumor with large mesenteric masses (larger than 2 cm) and/or extensive nodal deposits (12 or greater), especially those that encase the superior mesenteric vessels. (from AJCC 8th Ed.)
A term that refers to the staging of a jejunal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to small bowel ""carcinoid"" tumors (NET G1 and G2, and rare well-differentiated G3) arising in the jejunum. This classification system does not apply to high-grade neuroendocrine carcinomas, mixed adenoneuroendocrine carcinomas, and neuroendocrine tumors of the duodenum. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor invading lamina propria or submucosa and measuring 1 cm or less in size. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T2, N0, M0); (T3, N0, M0). T2: Tumor invading muscularis propria or measuring more than 1 cm in size. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T1, N1, N2, M0); (T2, N1, N2, M0); (T3, N1, N2, M0); (T4, N0, M0); (T4, N1, N2, M0). T1: Tumor invading lamina propria or submucosa and measuring 1 cm or less in size. T2: Tumor invading muscularis propria or measuring more than 1 cm in size. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. T4: Tumor invading visceral peritoneum (serosa) or other organs or adjacent structures. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis in less than 12 nodes. N2: Large mesenteric masses (larger than 2 cm) and/or extensive nodal deposits (12 or greater), especially those that encase the superior mesenteric vessels. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: (T1, N0, N1, N2, M1); (T2, N0, N1, N2, M1); (T3, N0, N1, N2, M1); (T4, N0, N1, N2, M1). T1: Tumor invading lamina propria or submucosa and measuring 1 cm or less in size. T2: Tumor invading muscularis propria or measuring more than 1 cm in size. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. T4: Tumor invading visceral peritoneum (serosa) or other organs or adjacent structures. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis in less than 12 nodes. N2: Large mesenteric masses (larger than 2 cm) and/or extensive nodal deposits (12 or greater), especially those that encase the superior mesenteric vessels. M1: Distant metastasis. (AJCC 8th ed.)
A term that refers to the staging of an ileal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to small bowel ""carcinoid"" tumors (NET G1 and G2, and rare well-differentiated G3) arising in the ileum. This classification system does not apply to high-grade neuroendocrine carcinomas, mixed adenoneuroendocrine carcinomas, and neuroendocrine tumors of the duodenum. (from AJCC 8th Ed.)
A term that refers to the staging of a digestive system neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system.
A finding about one or more characteristics of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to appendiceal NETs (carcinoid tumors) (NET G1 and G2, and rare well-differentiated G3). It does not apply to high-grade neuroendocrine carcinomas (NEC), goblet cell carcinoids, mixed adenocarcinomas, and adenocarcinomas of the appendix. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Appendix neuroendocrine tumor without evidence of distant metastasis. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor with distant metastasis. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor with metastasis confined to liver. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor with metastasis in at least one extrahepatic site (e.g., lung, ovary, nonregional lymph node, peritoneum, bone). (from AJCC 8th Ed.)
Appendix neuroendocrine tumor with both hepatic and extrahepatic metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Appendix neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor with no evidence of primary tumor. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor measuring 2 cm or less in greatest dimension. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor measuring more than 2 cm but less than or equal to 4 cm. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor measuring more than 4 cm or with subserosal invasion or involvement of the mesoappendix. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor perforating the peritoneum or directly invading other adjacent organs or structures (excluding direct mural extension to adjacent subserosa of adjacent bowel), e.g., abdominal wall and skeletal muscle. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Appendix neuroendocrine tumor in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor without regional lymph node metastasis. (from AJCC 8th Ed.)
Appendix neuroendocrine tumor with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of an appendiceal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This staging system applies to appendiceal NETs (carcinoid tumors) (NET G1 and G2, and rare well-differentiated G3). High-grade neuroendocrine carcinomas (NEC), goblet cell carcinoids, mixed adenocarcinomas, and adenocarcinomas of the appendix are not staged using this staging system. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor measuring 2 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T2, N0, M0); (T3, N0, M0). T2: Tumor measuring more than 2 cm but less than or equal to 4 cm. T3: Tumor measuring more than 4 cm or with subserosal invasion or involvement of the mesoappendix. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0); (T4, N0, M0); (T4, N1, M0). T1: Tumor measuring 2 cm or less in greatest dimension. T2: Tumor measuring more than 2 cm but less than or equal to 4 cm. T3: Tumor measuring more than 4 cm or with subserosal invasion or involvement of the mesoappendix. T4: Tumor perforating the peritoneum or directly invading other adjacent organs or structures (excluding direct mural extension to adjacent subserosa of adjacent bowel), e.g., abdominal wall and skeletal muscle. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: (T1, N0, N1, M1); (T2, N0, N1, M1); (T3, N0, N1, M1); (T4, N0, N1, M1). T1: Tumor measuring 2 cm or less in greatest dimension. T2: Tumor measuring more than 2 cm but less than or equal to 4 cm. T3: Tumor measuring more than 4 cm or with subserosal invasion or involvement of the mesoappendix. T4: Tumor perforating the peritoneum or directly invading other adjacent organs or structures (excluding direct mural extension to adjacent subserosa of adjacent bowel), e.g., abdominal wall and skeletal muscle. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M1: Distant metastasis. (AJCC 8th ed.)
A finding about one or more characteristics of a colorectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to colorectal ""carcinoid"" tumors (neuroendocrine tumor G1 and G2, and rare-well differentiated G3). It does not apply to high-grade neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas of the colon and rectum. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of a colorectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of a colorectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Colorectal neuroendocrine tumor with distant metastasis. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor with metastasis confined to liver. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor with metastasis in at least one extrahepatic site (e.g., lung, ovary, nonregional lymph node, peritoneum, bone). (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor with both hepatic and extrahepatic metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a colorectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of a colorectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of a colorectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Colorectal neuroendocrine tumor in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor without regional lymph node metastasis. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor with regional lymph node metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a colorectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Colorectal neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor with no evidence of primary tumor. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor invading the lamina propria or submucosa and measuring 2 cm or less. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor measuring less than 1 cm in greatest dimension. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor measuring 1-2 cm in greatest dimension. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor invading the muscularis propria or measuring more than 2 cm with invasion of the lamina propria or submucosa. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. (from AJCC 8th Ed.)
Colorectal neuroendocrine tumor invading the visceral peritoneum (serosa) or other organs or adjacent structures. (from AJCC 8th Ed.)
A stage of nuclear sclerotic cataract marked by mild yellowing and sclerosis of the lens nucleus. (Modified LOCS II)
A stage of nuclear sclerotic cataract marked by moderate yellowing and sclerosis of the lens nucleus. (Modified LOCS II)
A stage of nuclear sclerotic cataract marked by pronounced yellowing and sclerosis of the lens nucleus. (Modified LOCS II)
A stage of nuclear sclerotic cataract marked by severe yellowing and sclerosis of the lens nucleus. (Modified LOCS II)
A stage of cortical cataract characterized by 10% of the intrapupillary space obscured by opacity. (Modified LOCS II)
A stage of cortical cataract characterized by 10-50% of the intrapupillary space obscured by opacity. (Modified LOCS II)
A stage of cortical cataract characterized by 50-90% of the intrapupillary space obscured by opacity. (Modified LOCS II)
A stage of cortical cataract characterized by greater than 90% of the intrapupillary space obscured by opacity. (Modified LOCS II)
A stage of posterior subcapsular cataract characterized by 3% of the posterior capsule obscured by opacity. (Modified LOCS II)
A stage of posterior subcapsular cataract characterized by 30% of the posterior capsule obscured by opacity. (Modified LOCS II)
A stage of posterior subcapsular cataract characterized by 50% of the posterior capsule obscured by opacity. (Modified LOCS II)
A stage of posterior subcapsular cataract characterized by greater than 50% of the posterior capsule obscured by opacity. (Modified LOCS II)
A term that refers to the staging of a colorectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This staging system applies to colorectal ""carcinoid"" tumors (neuroendocrine tumor G1 and G2, and rare-well differentiated G3). High-grade neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas of the colon and rectum are not staged using this staging system. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor invading the lamina propria or submucosa and measuring 2 cm or less. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T2, N0, M0. T2: Tumor invading the muscularis propria or measuring more than 2 cm with invasion of the lamina propria or submucosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T3, N0, M0. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: T4, N0, M0. T4: Tumor invading the visceral peritoneum (serosa) or other organs or adjacent structures. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T1, N1, M0); (T2, N1, M0); (T3, N1, M0); (T4, N1, M0). T1: Tumor invading the lamina propria or submucosa and measuring 2 cm or less. T2: Tumor invading the muscularis propria or measuring more than 2 cm with invasion of the lamina propria or submucosa. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. T4: Tumor invading the visceral peritoneum (serosa) or other organs or adjacent structures. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: (T1, Any N, M1); (T2, Any N, M1); (T3, Any N, M1); (T4, Any N, M1). T1: Tumor invading the lamina propria or submucosa and measuring 2 cm or less. T2: Tumor invading the muscularis propria or measuring more than 2 cm with invasion of the lamina propria or submucosa. T3: Tumor invading through the muscularis propria into subserosal tissue without penetration of overlying serosa. T4: Tumor invading the visceral peritoneum (serosa) or other organs or adjacent structures. M1: Distant metastasis. (AJCC 8th ed.)
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the colon.
A well differentiated, low or intermediate grade tumor with neuroendocrine differentiation that arises from the rectum.
A term that refers to the staging of a colon neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This staging system applies to colon ""carcinoid"" tumors (neuroendocrine tumor G1 and G2, and rare-well differentiated G3). High-grade neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas of the colon are not staged using this staging system. (from AJCC 8th Ed.)
The volume of blood remaining in a heart chamber at end ventricular diastole.
The volume of blood remaining in a heart chamber at end ventricular systole.
The percent or fraction of the right ventricular end diastolic volume ejected in systole, which is calculated as the right ventricular stroke volume divided by the right ventricular end diastolic volume.
A visual estimation of the volume of blood ejected from the right ventricle during ventricular systole.
An electrocardiographic finding of a P wave that either does not conduct to the ventricle or that does not result in ventricular activation.
An electrocardiographic finding of a compensatory supraventricular complex that occurs following a prolonged RR interval. (CDISC)
An assessment of the disease response to therapy within the involved liver.
An assessment of the response to the therapy of the non-target enhancing lesion.
An assessment of the response to the therapy of the non-target non-enhancing lesion.
An assessment of the disease response to therapy within the involved spleen.
A term that refers to the staging of a rectal neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This staging system applies to rectal ""carcinoid"" tumors (neuroendocrine tumor G1 and G2, and rare-well differentiated G3). High-grade neuroendocrine carcinomas and mixed adenoneuroendocrine carcinomas of the rectum are not staged using this staging system. (from AJCC 8th Ed.)
Human autologous T-lymphocytes genetically modified to express a T-cell receptor (TCR) that specifically targets human melanoma-associated antigen A3 (MAGE-A3) and MAGE-A6 (MAGEA3/A6; MAGE-A3/A6), with potential antineoplastic activity. Peripheral blood mononuclear cells (PBMCs) are isolated from a patient, transduced with a gene expressing a TCR specific for the MAGE-A3/A6 antigens, expanded ex vivo, and reintroduced into the patient. Then, the autologous MAGE-A3/A6-specific TCR gene engineered lymphocytes KITE-718 target and bind to tumor cells expressing the MAGE-A3 and/or MAGE-A6 antigens. This halts the growth of and kills MAGE-A3/A6-expressing cancer cells. The tumor-associated antigens MAGE-A3 and MAGE-A6 are overexpressed on a variety of tumor cell types.
A finding about one or more characteristics of a pancreatic neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to well-differentiated neuroendocrine tumors arising in the pancreas. It does not apply to carcinomas of the pancreas, including high-grade (grade 3), poorly differentiated neuroendocrine carcinomas. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of a pancreatic neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of a pancreatic neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Pancreatic neuroendocrine tumor without evidence of distant metastasis. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor with distant metastasis. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor with metastasis confined to liver. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor with metastasis in at least one extrahepatic site (e.g., lung, ovary, nonregional lymph node, peritoneum, bone). (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor with both hepatic and extrahepatic metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a pancreatic neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of a pancreatic neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of a pancreatic neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Pancreatic neuroendocrine tumor in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor limited to the pancreas and measuring less than 2 cm. Limited to the pancreas means there is no invasion of adjacent organs (stomach, spleen, colon, adrenal gland) or the wall of large vessels (celiac axis or the superior mesenteric artery). Extension of tumor into peripancreatic adipose tissue is not a basis for staging. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor limited to the pancreas and measuring 2-4 cm. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor limited to the pancreas and measuring more than 4 cm; or tumor invading the duodenum or bile duct. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor invading adjacent organs (stomach, spleen, colon, adrenal gland) or the wall of large vessels (celiac axis or the superior mesenteric artery). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a pancreatic neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Pancreatic neuroendocrine tumor in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor without regional lymph node involvement. (from AJCC 8th Ed.)
Pancreatic neuroendocrine tumor with regional lymph node involvement. (from AJCC 8th Ed.)
A term that refers to the staging of a pancreatic neuroendocrine tumor, following the rules of the TNM AJCC v8 classification system. This staging system applies to well-differentiated neuroendocrine tumors arising in the pancreas. Carcinomas of the pancreas, including high-grade (grade 3), poorly differentiated neuroendocrine carcinomas are not staged using this staging system. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor limited to the pancreas and measuring less than 2 cm. N0: No regional lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T2, N0, M0); (T3, N0, M0). T2: Tumor limited to the pancreas and measuring 2-4 cm. T3: Tumor limited to the pancreas and measuring more than 4 cm; or tumor invading the duodenum or bile duct. N0: No regional lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T4, N0, M0); (Any T, N1, M0). T4: Tumor invading adjacent organs (stomach, spleen, colon, adrenal gland) or the wall of large vessels (celiac axis or the superior mesenteric artery). N0: No regional lymph node involvement. N1: Regional lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
A response indicating that an individual has or had no pain and no disturbing body sensations.
A response indicating that an individual had mild pain or disturbing body sensations, but that they do or did not limit activities.
A response indicating that an individual has or had moderate pain or disturbing body sensations that limited a few activities.
A response indicating that an individual has or had moderate to severe pain or disturbing body sensations that limited some activities.
A response indicating that an individual has or had severe pain or disturbing body sensations that limited many activities.
A response indicating that an individual is or was fairly energetic, with no limitation of activities.
A response indicating that an individual has or had a moderate reduction in energy or pep that limited a few activities.
A response indicating that an individual has or had generally low energy or pep that limited some activities.
A response indicating that an individual has or had no energy or pep at all; felt drained, with many activities limited.
A response indicating that an individual feels or felt supported by spouse, family, and friends at most times.
A response indicating that an individual feels or felt supported by spouse, family, and friends a fair amount of the time.
A response indicating that an individual feels or felt supported by spouse, family, and friends only occasionally.
A response indicating that an individual feels or felt supported by spouse, family, and friends only rarely.
A response indicating that an individual is or was always able to express concerns to their doctor and get the needed information or advice.
A response indicating that an individual is or was able to express concerns to their doctor and get the needed information or advice most of the time.
A response indicating that an individual is or was able to express concerns to their doctor and get the needed information or advice some of the time.
A response indicating that an individual is or was rarely able to express concerns to their doctor and get the needed information or advice.
A response indicating that an individual is generally happy and free from worry, sadness, or frustration.
A response indicating that an individual has a little worry, sadness, or frustration.
A response indicating that an individual has moderate worry, sadness, or frustration.
A response indicating that an individual has quite a bit of worry, sadness, and frustration.
A response indicating that an individual has extreme worry, sadness, or frustration.
A response indicating that an individual feels or felt no urinary frequency or urgency.
A response indicating that an individual feels or felt a little urinary frequency or urgency, but it does not interfere with sleep or other activities.
A response indicating that an individual feels or felt some urinary frequency or urgency that interferes with sleep or other activities and that may make it necessary to plan ahead.
A response indicating that an individual feels or felt quite a bit of urinary frequency or urgency, making it necessary to be near a bathroom most of the time.
A response indicating that an individual feels or felt extreme urinary frequency or urgency, making it necessary to be near a bathroom always.
A response indicating that an individual never, under any circumstances leaks urine or loses bladder control.
A response indicating that an individual, on rare occasions, leaks urine or loses bladder control but that it does not interfere with any activities.
A response indicating that an individual occasionally leaks urine or loses bladder control and it interferes with a few activities.
A response indicating that an individual leaks urine or loses bladder control a moderate amount of the time and it interferes with some activities.
A response indicating that an individual leaks urine or has poor bladder control most of the time and it interferes with many activities.
A response indicating that an individual requires a clamp, catheter, or collecting bag because of leaking urine or poor bladder control.
A formulation of the tartrate salt form of vinorelbine, a semisynthetic vinca alkaloid, encapsulated within liposomes, with potential antineoplastic activity. Upon intravenous administration, vinorelbine binds to tubulin within tumor cells and prevents the formation of the mitotic spindle, resulting in cell cycle arrest, induction of apoptosis and an inhibition of tumor cell growth. Compared to the administration of vinorelbine alone, the liposomal formulation improves drug penetration into tumors and decreases drug clearance, thereby increasing vinorelbine's efficacy while lowering the toxicity profile.
A response indicating that an individual achieves/maintains full erections sufficient for intercourse.
A response indicating that an individual achieves/maintains erections sufficient for intercourse, but has some reduction in firmness.
A response indicating that an individual achieves/maintains erections sufficient for masturbation or foreplay only.
A response indicating that an individual achieves/maintains erections, but not firm enough for any sexual activity.
A response indicating that an individual achieves no erections at all.
A response indicating that an individual has or had their normal amount of sexual drive and interest.
An orally active, small molecule inhibitor of hypoxia inducible factor (HIF)-2alpha (HIF-2a), with potential antineoplastic activity. Upon oral administration, HIF-2alpha inhibitor PT2977 binds to and blocks the function of HIF-2alpha, thereby preventing HIF-2alpha heterodimerization and its subsequent binding to DNA. This results in decreased transcription and expression of HIF-2alpha downstream target genes, many of which regulate hypoxic signaling. This inhibits cell growth and survival of HIF-2alpha-expressing tumor cells. HIF-2alpha, the alpha subunit for the heterodimeric transcription factor HIF-2, is overexpressed in many cancers and promotes tumorigenesis.
A response indicating that an individual has or had a little decrease of sexual drive or interest.
A response indicating that an individual has or had no sexual drive or interest.
An anti-CD33/anti-CD3 bispecific tetravalent antibody, with potential immunostimulatory and antineoplastic activities. Anti-CD33/CD3 tetravalent bispecific monoclonal antibody AMV564 possesses two antigen-recognition and binding sites, one for the CD3 complex, a group of T-cell surface glycoproteins that complex with the T-cell receptor (TCR), and one for CD33, a tumor-associated antigen (TAA) overexpressed on the surface of a variety of tumor cell types. Upon infusion of AMV564, this bispecific antibody binds to CD3-expressing T-cells and CD33-expressing tumor cells, thereby crosslinking CD33-expressing tumor cells and cytotoxic T-lymphocytes (CTLs). This may result in a potent CTL-mediated cell lysis of CD33-expressing cells. CD33, a glycoprotein expressed by a variety of cancers, including the majority of acute myeloid leukemias (AMLs), and normal non-pluripotent hematopoietic stem cells, plays a key role in tumor initiation, proliferation and progression.
A Fc-modified monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-CTLA4 monoclonal antibody BMS-986218 targets and binds to CTLA4 expressed on T-cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system. Removal of the fucose sugar units from the antibody's Fc region, enhances its activity and decreases the toxicity of BMS-986218.
A response indicating that an individual has or had a moderate decrease of sexual drive or interest.
A response indicating that an individual has or had a substantial decrease of sexual drive or interest.
A response indicating that an individual has or had no diarrhea, rectal discomfort, or constipation.
A response indicating that an individual occasionally has or had diarrhea, rectal discomfort, or constipation.
A response indicating that an individual frequently has or had diarrhea, rectal discomfort, or constipation.
A response indicating that an individual nearly always has or had diarrhea, rectal discomfort, or constipation.
A molecular genetic abnormality indicating the presence of a mutation in exon 2 of the KRAS gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 4 of the KRAS gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 2 of the NRAS gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 3 of the NRAS gene.
A molecular genetic abnormality indicating the presence of a mutation in exon 4 of the NRAS gene.
Carcinoma of the mammary gland that occurs in a hamster.
A T-cell leukemia in which there is a persistent increase in the number of large granular lymphocytes in the peripheral blood and occurring in a cat.
A nucleotide substitution at position 1474 of the coding sequence of the EGFR gene where adenine has been mutated to cytosine.
A nucleotide substitution at position 1476 of the coding sequence of the EGFR gene where cytosine has been mutated to adenine.
A change in the amino acid residue at position 492 in the epidermal growth factor receptor protein where serine has been replaced by arginine.
A carcinoma that originates from the rectum and has spread to the liver.
A variation in the amino acid sequence for the hepatocyte growth factor receptor protein.
A change in the amino acid residue at position 1003 in the hepatocyte growth factor receptor protein where tyrosine has been replaced by another amino acid.
A finding about one or more characteristics of thoracic cancer, following the rules of the TNM AJCC v8 classification system. It refers to thymic tumors, lung carcinoma, and malignant pleural mesothelioma.
A finding about one or more characteristics of a thymic tumor, following the rules of the TNM AJCC v8 classification system. This classification system applies to thymomas, thymic carcinomas, thymic neuroendocrine tumors, and combined thymic carcinomas. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of a thymic tumor, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of a thymic tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Thymic tumor without evidence of pleural, pericardial, or distant metastasis. (from AJCC 8th Ed.)
Thymic tumor with pleural, pericardial, or distant metastasis. (from AJCC 8th Ed.)
Thymic tumor with separate pleural or pericardial nodule(s). (from AJCC 8th Ed.)
Thymic tumor with pulmonary intraparenchymal nodule or distant organ metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a thymic tumor, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of a thymic tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of a thymic tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Thymic tumor in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Thymic tumor without evidence of primary tumor. (from AJCC 8th Ed.)
Thymic tumor which is encapsulated or extends into the mediastinal fat; may involve the mediastinal pleura. (from AJCC 8th Ed.)
Thymic tumor with no mediastinal pleura involvement. (from AJCC 8th Ed.)
Thymic tumor with direct invasion of mediastinal pleura. (from AJCC 8th Ed.)
Thymic tumor with direct invasion of the pericardium (either partial or full thickness). (from AJCC 8th Ed.)
Thymic tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall, or extrapericardial pulmonary artery or veins. (from AJCC 8th Ed.)
Thymic tumor with invasion into any of the following: aorta (ascending, arch, or descending), arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a thymic tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Thymic tumor in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Thymic tumor without regional lymph node metastasis. (from AJCC 8th Ed.)
Thymic tumor with metastasis in anterior (perithymic) lymph nodes. (from AJCC 8th Ed.)
Thymic tumor with metastasis in deep intrathoracic or cervical lymph nodes. (from AJCC 8th Ed.)
A term that refers to the staging of a thymic epithelial neoplasm, following the rules of the TNM AJCC v8 classification system. This staging system applies to thymomas, thymic carcinomas, thymic neuroendocrine tumors, and combined thymic carcinomas. (from AJCC 8th Ed.)
Stage I includes: T1a, b, N0, M0. T1a: Tumor with no mediastinal pleura involvement. T1b: Tumor with direct invasion of mediastinal pleura. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Tumor with direct invasion of the pericardium (either partial or full thickness). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T3, N0, M0); IIIB: (T4, N0, M0). T3: Tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall, or extrapericardial pulmonary artery or veins. T4: Tumor with invasion into any of the following: aorta (ascending, arch, or descending), arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: T3, N0, M0. T3: Tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall, or extrapericardial pulmonary artery or veins. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: T4, N0, M0. T4: Tumor with invasion into any of the following: aorta (ascending, arch, or descending), arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (Any T, N1, M0); (Any T, N0,1, M1a); IVB: (Any T, N2, M0, M1a); (Any T, Any N, M1b). N0: No regional lymph node metastasis. N1: Metastasis in anterior (perithymic) lymph nodes. N2: Metastasis in deep intrathoracic or cervical lymph nodes. M0: No distant metastasis. M1a: Separate pleural or pericardial nodule(s). M1b: Pulmonary intraparenchymal nodule or distant organ metastasis. (AJCC 8th ed.)
Stage IVA includes: (Any T, N1, M0); (Any T, N0,1, M1a). N0: No regional lymph node metastasis. N1: Metastasis in anterior (perithymic) lymph nodes. M0: No distant metastasis. M1a: Separate pleural or pericardial nodule(s). (AJCC 8th ed.)
Stage IVB includes: (Any T, N2, M0, M1a); (Any T, Any N, M1b). N2: Metastasis in deep intrathoracic or cervical lymph nodes. M0: No distant metastasis. M1a: Separate pleural or pericardial nodule(s). M1b: Pulmonary intraparenchymal nodule or distant organ metastasis. (AJCC 8th ed.)
A response indicating that something happens or happened for a very short time.
A term that refers to the staging of thymoma, following the rules of the TNM AJCC v8 classification system.
A term that refers to the staging of pleural malignant mesothelioma, following the rules of the TNM AJCC v7 classification system.
A finding about one or more characteristics of pleural malignant mesothelioma, following the rules of the TNM AJCC v8 classification system. This classification system applies to pleural diffuse malignant mesothelioma only. Localized pleural malignant mesotheliomas and other primary tumors of the pleura are not included in this classification. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of pleural malignant mesothelioma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of pleural malignant mesothelioma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Pleural malignant mesothelioma without distant metastasis. (from AJCC 8th Ed.)
Pleural malignant mesothelioma with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of pleural malignant mesothelioma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of pleural malignant mesothelioma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of pleural malignant mesothelioma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Pleural malignant mesothelioma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Pleural malignant mesothelioma without evidence of primary tumor. (from AJCC 8th Ed.)
Pleural malignant mesothelioma with tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of diaphragmatic muscle and/or extension of tumor from visceral pleura into the underlying pulmonary parenchyma. (from AJCC 8th Ed.)
Pleural malignant mesothelioma in which the tumor is locally advanced but potentially resectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of the endothoracic fascia, extension into the mediastinal fat, solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall, and/or nontransmural involvement of the pericardium. (from AJCC 8th Ed.)
Pleural malignant mesothelioma in which the tumor is locally advanced and technically unresectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction, direct transdiaphragmatic extension of tumor to the peritoneum, direct extension of tumor to the contralateral pleura, direct extension of tumor to mediastinal organs, direct extension of tumor into the spine, and/or tumor extending through to the internal surface of the pericardium with or without a pericardial effusion; or tumor involving the myocardium. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of pleural malignant mesothelioma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Pleural malignant mesothelioma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Pleural malignant mesothelioma without regional lymph node metastases. (from AJCC 8th Ed.)
Pleural malignant mesothelioma with metastases in the ipsilateral bronchopulmonary, hilar, or mediastinal (including the internal mammary, peridiaphragmatic, pericardial fat pad, or intercostal) lymph nodes. (from AJCC 8th Ed.)
Pleural malignant mesothelioma with metastases in the contralateral mediastinal, ipsilateral, or contralateral supraclavicular lymph nodes. (from AJCC 8th Ed.)
A term that refers to the staging of pleural malignant mesothelioma, following the rules of the TNM AJCC v8 classification system. This staging system applies to pleural diffuse malignant mesothelioma only. Localized pleural malignant mesotheliomas and other primary tumors of the pleura are not staged using this staging system. (from AJCC 8th Ed.)
Stage IIIA includes: T3, N1, M0. T3: Tumor is locally advanced but potentially resectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of the endothoracic fascia, extension into the mediastinal fat, solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall, and/or nontransmural involvement of the pericardium. N1: Metastases in the ipsilateral bronchopulmonary, hilar, or mediastinal (including the internal mammary, peridiaphragmatic, pericardial fat pad, or intercostal) lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T1-3, N2, M0); (T4, Any N, M0). T1: Tumor limited to the ipsilateral parietal with or without involvement of visceral pleura, mediastinal pleura, and diaphragmatic pleura. T2: Tumor involving each of the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of diaphragmatic muscle and/or extension of tumor from visceral pleura into the underlying pulmonary parenchyma. T3: Tumor is locally advanced but potentially resectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: involvement of the endothoracic fascia, extension into the mediastinal fat, solitary, completely resectable focus of tumor extending into the soft tissues of the chest wall, and/or nontransmural involvement of the pericardium. T4: Tumor is locally advanced and technically unresectable. The tumor involves all the ipsilateral pleural surfaces (parietal, mediastinal, diaphragmatic, and visceral pleura) with at least one of the following features: diffuse extension or multifocal masses of tumor in the chest wall, with or without associated rib destruction, direct transdiaphragmatic extension of tumor to the peritoneum, direct extension of tumor to the contralateral pleura, direct extension of tumor to mediastinal organs, direct extension of tumor into the spine, and/or tumor extending through to the internal surface of the pericardium with or without a pericardial effusion; or tumor involving the myocardium. N2: Metastases in the contralateral mediastinal, ipsilateral, or contralateral supraclavicular lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
A malignant germ cell tumor that affects the peritoneum.
A change in the nucleotide sequence in a PDGFR family gene.
An inhibitor of NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) activating enzyme E1 (NAE), with potential antineoplastic activity. Upon administration, TAS4464 selectively binds to and inhibits NAE, which prevents NAE/NEDD8-mediated signaling and prevents the NEDD8 conjugation of cullin-RING ligase complexes (CRLs). This inactivates the CRLs leading to an accumulation of CRL substrate proteins, such as CDT1, p27, p21 and phosphorylated IkappaB, and inactivates nuclear factor-kappaB (NF-kB) as well as downregulates anti-apoptotic proteins. This causes cell cycle dysregulation, induces apoptosis, and inhibits tumor cell proliferation and survival. NAE catalyzes the first step in the NEDD8 conjugation (neddylation) pathway which controls cancer cell growth and survival through activation of CRLs.
A change in the nucleotide sequence in a VEGFR family gene.
A change in the nucleotide sequence in a JAK family gene.
A change in the nucleotide sequence in a STAT family gene.
A change in the nucleotide sequence in a MEK family gene.
A change in the nucleotide sequence in a ERK family gene.
An orally bioavailable inhibitor of the tyrosine kinase receptor colony stimulating factor 1 receptor (CSF1R; CSF-1R; C-FMS; CD115; M-CSFR), with potential antineoplastic, macrophage checkpoint-inhibitory and immunomodulating activities. Upon administration, CSF1R inhibitor DCC-3014 targets and binds to CSF1R expressed on monocytes, macrophages, and osteoclasts and inhibits the binding of the CSF1R ligands colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34), to CSF1R. This prevents CSF1R activation and CSF1R-mediated signaling in these cells. This blocks the production of inflammatory mediators by macrophages and monocytes and reduces inflammation. By blocking the recruitment to the tumor microenvironment and activity of CSF1R-dependent tumor-associated macrophages (TAMs), DCC-3014 inhibits the immunomodulating activity by macrophages and enhances T-cell infiltration and antitumor T-cell immune responses, which inhibits the proliferation of tumor cells. TAMs play key roles in the tumor microenvironment and allow for immune suppression; TAMs promote inflammation, tumor cell proliferation, angiogenesis, invasiveness and survival.
A change in the nucleotide sequence in a RAF family gene.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody against the ganglioside GD3, a surface antigen expressed on many malignant melanoma cells, and linked to an as of yet not fully elucidated chemotherapeutic agent, with potential antineoplastic activity. Upon administration of the ADC PF-06688992, the antibody moiety targets and binds to GD3 expressed on melanoma cells. Upon internalization, the chemotherapeutic agent specifically kills the GD3-positive cells. GD3 represents a major surface marker on most human melanoma cells and is not expressed on most other types of normal, healthy cells.
A squamous cell carcinoma that arises from the head and neck region and is not amenable to surgical resection.
A formulation composed of three agents in a fixed ratio: two chemotherapeutic agents, the platinum compound cisplatin and the vinca alkaloid vinblastine, and a proprietary amphiphilic excipient that acts as a penetration enhancer, with potential antineoplastic activity. Upon intra-tumoral (IT) injection of INT230-6, the dispersion/cell penetration enhancer excipient of INT230-6 facilitates dispersion of the two drugs throughout the tumor tissue and enables increased cellular uptake of these agents into tumor cells. Once inside the cell, cisplatin forms highly reactive, charged, platinum complexes which bind to nucleophilic groups such as GC-rich sites in DNA, which results in apoptosis and cell growth inhibition. Vinblastine kills the tumor cells through binding to tubulin and thereby inhibits microtubule formation, resulting in disruption of the mitotic spindle assembly and cell cycle arrest of tumor. In addition, the tumor cell killing leads to recruitment of dendritic cells (DCs) and induces a tumor-specific T-cell-mediated immune response that attacks both the injected tumor and distant tumor lesions. Local administration of both cisplatin and vinblastine, without the diffusion/penetration enhancer, results in to poor diffusion and a lack of cellular uptake of the agents; INT230-6 increases the intracellular concentration of cisplatin and vinblastine, thereby improving efficacy.
A finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v8 classification system. This classification system derives from analyses of the new retrospective and prospective databases of the International Association for the Study of Lung Cancer (IASLC). These databases contain information on patients diagnosed with lung cancer from 1999 to 2010 originating from 35 different databases in 16 countries around the world. This classification system applies to carcinomas of the lung, including non-small cell and small cell carcinomas, and bronchopulmonary carcinoid tumors. It does not apply to sarcomas or other rare tumors of the lung. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Lung cancer without distant metastasis. (from AJCC 8th Ed.)
Lung cancer with distant metastasis. (from AJCC 8th Ed.)
Lung cancer with separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodules or malignant pleural or pericardial effusion. Most pleural (pericardial) effusions with lung cancer are a result of the tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and not an exudate. If these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging descriptor. (from AJCC 8th Ed.)
Lung cancer with single extrathoracic metastasis in a single organ (including involvement of a single nonregional node). (from AJCC 8th Ed.)
Lung cancer with multiple extrathoracic metastases in a single organ or in multiple organs. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Lung cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Lung cancer without evidence of primary tumor. (from AJCC 8th Ed.)
Lung cancer with a finding of carcinoma in situ. Squamous cell carcinoma in situ (SCIS). Adenocarcinoma in situ (AIS): adenocarcinoma with pure lepidic pattern, 3 cm or less in greatest dimension. (from AJCC 8th Ed.)
Lung cancer with tumor 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the main bronchus). (from AJCC 8th Ed.)
Lung cancer with minimally invasive adenocarcinoma: adenocarcinoma (3 cm or less in greatest dimension) with a predominantly lepidic pattern and 5 mm or less invasion in greatest dimension. (from AJCC 8th Ed.)
Lung cancer with tumor 1 cm or less in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon. (from AJCC 8th Ed.)
Lung cancer with tumor measuring more than 1 cm but 2 cm or less in greatest dimension. (from AJCC 8th Ed.)
Lung cancer with tumor measuring more than 2 cm but 3 cm or less in greatest dimension. (from AJCC 8th Ed.)
Lung cancer with tumor measuring more than 3 cm but 5 cm or less in greatest dimension or having any of the following features: involves the main bronchus regardless of distance to the carina, but without involvement of the carina, invades visceral pleura (extends through the elastic layer-PL1 or extends to the surface of the visceral pleura-PL2), or is associated with atelectasis or obstructive pneumonitis that extends to the hilar region, involving part or all of the lung. T2 tumors with these features are classified as T2a if they measure 4 cm or less or if the size cannot be determined and T2b if they measure more than 4 cm but 5 cm or less in greatest dimension. (from AJCC 8th Ed.)
Lung cancer with tumor measuring more than 3 cm but 4 cm or less in greatest dimension. (from AJCC 8th Ed.)
Lung cancer with tumor measuring more than 5 cm but 7 cm or less in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary. (from AJCC 8th Ed.)
Lung cancer with tumor measuring more than 7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of lung cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Lung cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Lung cancer without regional lymph node metastasis. (from AJCC 8th Ed.)
Lung cancer with metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension. (from AJCC 8th Ed.)
Lung cancer with metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s). (from AJCC 8th Ed.)
Lung cancer with metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s). (from AJCC 8th Ed.)
A monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1, PCD-1; PDCD1) protein, with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-1 monoclonal antibody AGEN2034 binds to PD-1, and thereby blocks its binding to the PD-1 ligand programmed cell death-1 ligand 1 (PD-L1), and prevents the activation of its downstream signaling pathways. This may restore immune function through the activation of cytotoxic T-cells. PD-1, a transmembrane protein in the immunoglobulin superfamily expressed on activated T-cells, negatively regulates T-cell activation and effector function when activated by its ligand; it plays an important role in tumor evasion from host immunity.
A synthetic peptide-based, personalized cancer vaccine consisting of multiple patient-specific tumor peptides, which are immunogenic and unique to the patient's tumor, combined with the immunostimulant polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC), with potential immunomodulating and antineoplastic activities. Upon vaccination with the personalized genomic vaccine 001 (PGV001), the peptides stimulate the host immune system to mount a specific and potent cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis. The adjuvant Poly-ICLC is added to boost the immune response to the peptides and together will expand immune cells to target cancer. The adjuvant poly-ICLC is a ligand for toll-like receptor-3 (TLR3) and induces the release of cytokines which may help to boost the immune response against the selected neoantigens.
A term that refers to the staging of lung cancer, following the rules of the TNM AJCC v8 classification system. This staging system derives from analyses of the new retrospective and prospective databases of the International Association for the Study of Lung Cancer (IASLC). These databases contain information on patients diagnosed with lung cancer from 1999 to 2010 originating from 35 different databases in 16 countries around the world. This staging system applies to carcinomas of the lung, including non-small cell and small cell carcinomas, and bronchopulmonary carcinoid tumors. It does not apply to sarcomas or other rare tumors of the lung. (from AJCC 8th Ed.)
Occult lung cancer includes: TX, N0, M0. TX: Primary tumor cannot be assessed. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. Squamous cell carcinoma in situ (SCIS). Adenocarcinoma in situ (AIS): adenocarcinoma with pure lepidic pattern, 3 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: IA1: (T1mi, N0, M0); (T1a, N0, M0); IA2: (T1b, N0, M0); IA3: (T1c, N0, M0); IB: (T2a, N0, M0). T1mi: Minimally invasive adenocarcinoma: adenocarcinoma (3 cm or less in greatest dimension) with a predominantly lepidic pattern and 5 mm or less invasion in greatest dimension. T1a: Tumor measuring 1 cm or less in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon. T1b: Tumor measuring more than 1 cm but 2 cm or less in greatest dimension. T1c: Tumor measuring more than 2 cm but 3 cm or less in greatest dimension. T2a: Tumor measuring more than 3 cm but 4 cm or less in greatest dimension. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA1 includes: IA1: (T1mi, N0, M0); (T1a, N0, M0). T1mi: Minimally invasive adenocarcinoma: adenocarcinoma (3 cm or less in greatest dimension) with a predominantly lepidic pattern and 5 mm or less invasion in greatest dimension. T1a: Tumor measuring 1 cm or less in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA2 includes: T1b, N0, M0. T1b: Tumor measuring more than 1 cm but 2 cm or less in greatest dimension. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA3 includes: T1c, N0, M0. T1c: Tumor measuring more than 2 cm but 3 cm or less in greatest dimension. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage IB includes: T2a, N0, M0. T2a: Tumor measuring more than 3 cm but 4 cm or less in greatest dimension. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: (T2b, N0, M0); IIB: (T1a, N1, M0); (T1b, N1, M0); (T1c, N1, M0); (T2a, N1, M0); (T2b, N1, M0); (T3, N0, M0). T2b: Tumor measuring more than 4 cm but 5 cm or less in greatest dimension. T1a: Tumor measuring 1 cm or less in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon. T1b: Tumor measuring more than 1 cm but 2 cm or less in greatest dimension. T1c: Tumor measuring more than 2 cm but 3 cm or less in greatest dimension. T2a: Tumor measuring more than 3 cm but 4 cm or less in greatest dimension. T3: Tumor measuring more than 5 cm but 7 cm or less in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary. N0: No regional lymph node metastases. N1: Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T2b, N0, M0. T2b: Tumor measuring more than 4 cm but 5 cm or less in greatest dimension. N0: No regional lymph node metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: (T1a, N1, M0); (T1b, N1, M0); (T1c, N1, M0); (T2a, N1, M0); (T2b, N1, M0); (T3, N0, M0). T1a: Tumor measuring 1 cm or less in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon. T1b: Tumor measuring more than 1 cm but 2 cm or less in greatest dimension. T1c: Tumor measuring more than 2 cm but 3 cm or less in greatest dimension. T2a: Tumor measuring more than 3 cm but 4 cm or less in greatest dimension. T2b: Tumor measuring more than 4 cm but 5 cm or less in greatest dimension. T3: Tumor measuring more than 5 cm but 7 cm or less in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary. N0: No regional lymph node metastases. N1: Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: (T1a, N2, M0); (T1b, N2, M0); (T1c, N2, M0); (T2a, N2, M0); (T2b, N2, M0); (T3, N1, M0); (T4, N0, M0); (T4, N1, M0); IIIB: (T1a, N3, M0); (T1b, N3, M0); (T1c, N3, M0); (T2a, N3, M0); (T2b, N3, M0); (T3, N2, M0); (T4, N2, M0); IIIC: (T3, N3, M0); (T4, N3, M0). T1a: Tumor measuring 1 cm or less in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon. T1b: Tumor measuring more than 1 cm but 2 cm or less in greatest dimension. T1c: Tumor measuring more than 2 cm but 3 cm or less in greatest dimension. T2a: Tumor measuring more than 3 cm but 4 cm or less in greatest dimension. T2b: Tumor measuring more than 4 cm but 5 cm or less in greatest dimension. T3: Tumor measuring more than 5 cm but 7 cm or less in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary. T4: Tumor measuring more than 7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary. N0: No regional lymph node metastases. N1: Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension. N2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s). N3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s). M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: (T1a, N2, M0); (T1b, N2, M0); (T1c, N2, M0); (T2a, N2, M0); (T2b, N2, M0); (T3, N1, M0); (T4, N0, M0); (T4, N1, M0). T1a: Tumor measuring 1 cm or less in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon. T1b: Tumor measuring more than 1 cm but 2 cm or less in greatest dimension. T1c: Tumor measuring more than 2 cm but 3 cm or less in greatest dimension. T2a: Tumor measuring more than 3 cm but 4 cm or less in greatest dimension. T2b: Tumor measuring more than 4 cm but 5 cm or less in greatest dimension. T3: Tumor measuring more than 5 cm but 7 cm or less in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary. T4: Tumor measuring more than 7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary. N0: No regional lymph node metastases. N1: Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension. N2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s). M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T1a, N3, M0); (T1b, N3, M0); (T1c, N3, M0); (T2a, N3, M0); (T2b, N3, M0); (T3, N2, M0); (T4, N2, M0). T1a: Tumor measuring 1 cm or less in greatest dimension. A superficial, spreading tumor of any size whose invasive component is limited to the bronchial wall and may extend proximal to the main bronchus also is classified as T1a, but these tumors are uncommon. T1b: Tumor measuring more than 1 cm but 2 cm or less in greatest dimension. T1c: Tumor measuring more than 2 cm but 3 cm or less in greatest dimension. T2a: Tumor measuring more than 3 cm but 4 cm or less in greatest dimension. T2b: Tumor measuring more than 4 cm but 5 cm or less in greatest dimension. T3: Tumor measuring more than 5 cm but 7 cm or less in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary. T4: Tumor measuring more than 7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary. N2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s). N3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s). M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIC includes: (T3, N3, M0); (T4, N3, M0). T3: Tumor measuring more than 5 cm but 7 cm or less in greatest dimension or directly invading any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal pericardium; or separate tumor nodule(s) in the same lobe as the primary. T4: Tumor measuring more than 7 cm or tumor of any size invading one or more of the following: diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that of the primary. N3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s). M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: IVA: (Any T, Any N, M1a); (Any T, Any N, M1b); IVB: (Any T, Any N, M1c). M1a: Tumor with separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodules or malignant pleural or pericardial effusion. Most pleural (pericardial) effusions with lung cancer are a result of the tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and not an exudate. If these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging descriptor. M1b: Tumor with single extrathoracic metastasis in a single organ (including involvement of a single nonregional node). M1c: Tumor with multiple extrathoracic metastases in a single organ or in multiple organs. (AJCC 8th ed.)
Stage IVA includes: (Any T, Any N, M1a); (Any T, Any N, M1b). M1a: Tumor with separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodules or malignant pleural or pericardial effusion. Most pleural (pericardial) effusions with lung cancer are a result of the tumor. In a few patients, however, multiple microscopic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonbloody and not an exudate. If these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging descriptor. M1b: Tumor with single extrathoracic metastasis in a single organ (including involvement of a single nonregional node). (AJCC 8th ed.)
Stage IVB includes: Any T, Any N, M1c. M1c: Tumor with multiple extrathoracic metastases in a single organ or in multiple organs. (AJCC 8th ed.)
Erdheim-Chester disease that does not respond to treatment.
A term that refers to the staging of lung adenocarcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of non-small cell lung carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of adenosquamous lung carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of large cell lung carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of squamous cell lung carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of small cell lung carcinoma, following the rules of the TNM AJCC v7 classification system.
The reemergence of diffuse intrinsic pontine glioma after a period of remission.
Diffuse intrinsic pontine glioma that is resistant to treatment.
A condition that is relevant to either disease states or models of disease in gerbils (Subfamily Gerbillinae.)
A subjective score of 8 on a visual analogue scale that ranges from 0: No Pain to 10: Excruciating.
A condition that is relevant to either disease states or models of disease in fish.
A paraganglioma-pheochromocytoma that is not associated with a clear genetic mutation.
A finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to osteosarcoma, chondrosarcoma, Ewing sarcoma, spindle cell sarcoma, hemangioendothelioma, angiosarcoma, fibrosarcoma/myofibroid sarcoma, chordoma, adamantinoma, and other cancers arising in the bone. It does not apply to primary malignant lymphoma of the bone and multiple myeloma. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Bone cancer without distant metastasis. (from AJCC 8th Ed.)
Bone cancer with distant metastasis. (from AJCC 8th Ed.)
Bone cancer with metastasis in the lung. (from AJCC 8th Ed.)
Bone cancer with metastasis in the bone or other distant sites. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of appendicular skeleton, trunk, skull, and facial bones cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Appendicular skeleton, trunk, skull, and facial bones cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Appendicular skeleton, trunk, skull, and facial bones cancer without evidence of primary tumor. (from AJCC 8th Ed.)
Appendicular skeleton, trunk, skull, and facial bones cancer with tumor measuring 8 cm or less in greatest dimension. (from AJCC 8th Ed.)
Appendicular skeleton, trunk, skull, and facial bones cancer with tumor measuring more than 8 cm in greatest dimension. (from AJCC 8th Ed.)
Appendicular skeleton, trunk, skull, and facial bones cancer with discontinuous tumors in the primary bone site. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of spine cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Spine cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Spine cancer without evidence of primary tumor. (from AJCC 8th Ed.)
Spine cancer with tumor confined to one vertebral segment or two adjacent vertebral segments. (from AJCC 8th Ed.)
Spine cancer with tumor confined to three adjacent vertebral segments. (from AJCC 8th Ed.)
Spine cancer with tumor confined to four or more adjacent vertebral segments, or any nonadjacent vertebral segments. (from AJCC 8th Ed.)
Spine cancer with tumor extending into the spinal canal or great vessels. (from AJCC 8th Ed.)
Spine cancer with tumor extending into the spinal canal. (from AJCC 8th Ed.)
Spine cancer with evidence of gross vascular invasion or tumor thrombus in the great vessels. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of pelvis cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Pelvis cancer without evidence of primary tumor. (from AJCC 8th Ed.)
Pelvis cancer with tumor confined to one pelvic segment with no extraosseous extension. (from AJCC 8th Ed.)
Pelvis cancer with tumor confined to one pelvic segment with no extraosseous extension and measuring 8 cm or less in greatest dimension. (from AJCC 8th Ed.)
Pelvis cancer with tumor confined to one pelvic segment with no extraosseous extension and measuring more than 8 cm in greatest dimension. (from AJCC 8th Ed.)
Pelvis cancer with tumor confined to one pelvic segment with extraosseous extension or two segments without extraosseous extension. (from AJCC 8th Ed.)
Pelvis cancer with tumor confined to one pelvic segment with extraosseous extension or two segments without extraosseous extension and measuring 8 cm or less in greatest dimension. (from AJCC 8th Ed.)
Pelvis cancer with tumor confined to one pelvic segment with extraosseous extension or two segments without extraosseous extension and measuring more than 8 cm in greatest dimension. (from AJCC 8th Ed.)
Pelvis cancer with tumor spanning two pelvic segments with extraosseous extension. (from AJCC 8th Ed.)
Pelvis cancer with tumor spanning two pelvic segments with extraosseous extension and measuring 8 cm or less in greatest dimension. (from AJCC 8th Ed.)
Pelvis cancer with tumor spanning two pelvic segments with extraosseous extension and measuring more than 8 cm in greatest dimension. (from AJCC 8th Ed.)
Pelvis cancer with tumor spanning three pelvic segments or crossing the sacroiliac joint. (from AJCC 8th Ed.)
Pelvis cancer with tumor involving the sacroiliac joint and extending medial to the sacral neuroforamen. (from AJCC 8th Ed.)
Pelvis cancer with tumor encasement of external iliac vessels or presence of gross tumor thrombus in major pelvic vessels. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of bone cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Bone cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Bone cancer without regional lymph node metastasis. (from AJCC 8th Ed.)
Bone cancer with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of bone cancer, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of appendicular skeleton, trunk, skull, and facial bones cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to osteosarcoma, chondrosarcoma, Ewing sarcoma, spindle cell sarcoma, hemangioendothelioma, angiosarcoma, fibrosarcoma/myofibroid sarcoma, chordoma, adamantinoma, and other cancers arising in the bone. It does not apply to primary malignant lymphoma of the bone and multiple myeloma. There are no AJCC prognostic stage groupings for spine and pelvis. (from AJCC 8th Ed.)
A change in the nucleotide sequence of the SMARCB1 gene.
The histological transformation of lung adenocarcinoma to either small cell lung carcinoma or squamous cell carcinoma. This occurs via acquisition of a T790M mutation in the EGFR gene in response to treatment with tyrosine kinase inhibitors and results in resistance to first-line tyrosine kinase inhibitors.
A molecular abnormality indicating rearrangement of the NFKB2 gene.
A change in the nucleotide sequence of the ESR1 gene.
A finding indicating elevated concentrations of human chorionic gonadotropin in the blood.
A term that refers to the staging of bone sarcoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of osteosarcoma, following the rules of the TNM AJCC v7 classification system.
A point mutation in the FLT3 gene that encodes an amino acid substitution in the receptor-type tyrosine-protein kinase FLT3 protein.
A point mutation in the KIT gene that encodes an amino acid substitution in the mast/stem cell growth factor receptor Kit protein.
A point mutation in a gene that is a member of the RAS gene family that encodes an amino acid substitution in a RAS family protein.
A point mutation in a gene that is a member of the RAF gene family that encodes an amino acid substitution in a RAF family protein.
A point mutation in a gene that is a member of the MAPK gene family that encodes an amino acid substitution in a MAPK family protein.
A point mutation in a gene that is a member of the MAP2K gene family that encodes an amino acid substitution in a MAP2K family protein.
A point mutation in a gene that is a member of the STAT gene family that encodes an amino acid substitution in a STAT family protein.
A point mutation in a gene that is a member of the JAK gene family that encodes an amino acid substitution in a JAK family protein.
A point mutation in a gene that is a member of the VEGFR gene family that encodes an amino acid substitution in a VEGFR family protein.
A point mutation in a gene that is a member of the PDGFR gene family that encodes an amino acid substitution in a PDGFR family protein.
A change in the nucleotide sequence of a gene that is a member of the NOTCH gene family.
A change in the nucleotide sequence of the CBL gene.
A change in the nucleotide sequence of the JAK3 gene.
The reemergence of cervical squamous cell carcinoma after a period of remission.
The reemergence of cervical adenosquamous carcinoma after a period of remission.
The reemergence of cervical adenocarcinoma after a period of remission.
A finding about one or more characteristics of soft tissue sarcoma, following the rules of the TNM AJCC v8 classification system. This classification system applies to soft tissue sarcomas that arise in the following areas: head and neck, trunk and extremities, gastrointestinal tract, genitourinary tract, viscera and retroperitoneum, gynecologic sites, breast, lung, pleura, mediastinum, and other unusual histologies and sites. It does not apply to desmoid tumor/deep fibromatosis (no AJCC staging system available) and Kaposi sarcoma (no AJCC staging system available; AIDS Clinical Trials Group system TIS (tumor, immune system, systemic illness) staging may be used). (from AJCC 8th Ed.)
A finding about one or more characteristics of soft tissue sarcoma of the head and neck, following the rules of the TNM AJCC v8 classification system. This classification system applies to soft tissue sarcomas of the head and neck except angiosarcoma, rhabdomyosarcoma of the embryonal and alveolar subtype, Kaposi sarcoma, and dermatofibrosarcoma protuberans, which do not share the same behavior and natural history. This is a new classification system that needs data collection before defining a stage grouping for head and neck sarcomas. Sarcomas of the orbit are staged according to the orbital sarcoma classification system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of soft tissue sarcoma of the head and neck, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of soft tissue sarcoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Soft tissue sarcoma of the head and neck without distant metastasis. (from AJCC 8th Ed.)
Soft tissue sarcoma of the head and neck with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma of the head and neck, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of soft tissue sarcoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of soft tissue sarcoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Soft tissue sarcoma of the head and neck in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Soft tissue sarcoma of the head and neck with tumor measuring 2 cm or less in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the head and neck with tumor measuring more than 2 cm but 4 cm or less in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the head and neck with tumor measuring more than 4 cm in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the head and neck with tumor invading adjoining structures. (from AJCC 8th Ed.)
Soft tissue sarcoma of the head and neck with tumor invading the orbit, skull base/dura, central compartment viscera, facial skeleton, or pterygoid muscles. (from AJCC 8th Ed.)
Soft tissue sarcoma of the head and neck with tumor invading the brain parenchyma, prevertebral muscle, central nervous system via perineural spread, or carotid artery encasement. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma of the head and neck, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Soft tissue sarcoma of the head and neck without regional lymph node metastases or unknown lymph node status. (from AJCC 8th Ed.)
Soft tissue sarcoma of the head and neck with regional lymph node metastasis. (from AJCC 8th Ed.)
A finding about one or more characteristics of soft tissue sarcoma of the trunk and extremities, following the rules of the TNM AJCC v8 classification system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of soft tissue sarcoma of the trunk and extremities, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of soft tissue sarcoma of the trunk and extremities, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Soft tissue sarcoma of the trunk and extremities with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma of the trunk and extremities, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of soft tissue sarcoma of the trunk and extremities, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of soft tissue sarcoma of the trunk and extremities, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Soft tissue sarcoma of the trunk and extremities in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Soft tissue sarcoma of the trunk and extremities with no evidence of primary tumor. (from AJCC 8th Ed.)
Soft tissue sarcoma of the trunk and extremities with tumor measuring 5 cm or less in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the trunk and extremities with tumor measuring more than 5 cm and less than or equal to 10 cm in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the trunk and extremities with tumor measuring more than 10 cm and less than or equal to 15 cm in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the trunk and extremities with tumor measuring more than 15 cm in greatest dimension. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma of the trunk and extremities, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Soft tissue sarcoma of the trunk and extremities without regional lymph node metastasis or unknown lymph node status. (from AJCC 8th Ed.)
Soft tissue sarcoma of the trunk and extremities with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of soft tissue sarcoma, following the rules of the TNM AJCC v8 classification system.
A term that refers to the staging of soft tissue sarcoma of the trunk and extremities, following the rules of the TNM AJCC v8 classification system.
Stage I includes: IA: (T1, N0, M0, G1, GX); IB: (T2, T3, T4, N0, M0, G1, GX). T1: Tumor measuring 5 cm or less in greatest dimension. T2: Tumor measuring more than 5 cm and less than or equal to 10 cm in greatest dimension. T3: Tumor measuring more than 10 cm and less than or equal to 15 cm in greatest dimension. T4: Tumor measuring more than 15 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. GX: Grade cannot be assessed. G1: Total differentiation, mitotic count and necrosis score of 2 or 3. (AJCC 8th ed.)
Stage IA includes: T1, N0, M0, G1, GX. T1: Tumor measuring 5 cm or less in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. GX: Grade cannot be assessed. G1: Total differentiation, mitotic count and necrosis score of 2 or 3. (AJCC 8th ed.)
Stage IB includes: T2, T3, T4, N0, M0, G1, GX. T2: Tumor measuring more than 5 cm and less than or equal to 10 cm in greatest dimension. T3: Tumor measuring more than 10 cm and less than or equal to 15 cm in greatest dimension. T4: Tumor measuring more than 15 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. GX: Grade cannot be assessed. G1: Total differentiation, mitotic count and necrosis score of 2 or 3. (AJCC 8th ed.)
Stage II includes: T1, N0, M0, G2, G3. T1: Tumor measuring 5 cm or less in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. G2: Total differentiation, mitotic count and necrosis score of 4 or 5. G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8. (AJCC 8th ed.)
Stage III includes: IIIA: (T2, N0, M0, G2, G3); IIIB: (T3, T4, N0, M0, G2, G3). T2: Tumor measuring more than 5 cm and less than or equal to 10 cm in greatest dimension. T3: Tumor measuring more than 10 cm and less than or equal to 15 cm in greatest dimension. T4: Tumor measuring more than 15 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. G2: Total differentiation, mitotic count and necrosis score of 4 or 5. G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8. (AJCC 8th ed.)
Stage IIIA includes: T2, N0, M0, G2, G3. T2: Tumor measuring more than 5 cm and less than or equal to 10 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. G2: Total differentiation, mitotic count and necrosis score of 4 or 5. G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8. (AJCC 8th ed.)
Stage IIIB includes: T3, T4, N0, M0, G2, G3. T3: Tumor measuring more than 10 cm and less than or equal to 15 cm in greatest dimension. T4: Tumor measuring more than 15 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. G2: Total differentiation, mitotic count and necrosis score of 4 or 5. G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8. (AJCC 8th ed.)
Stage IV includes: (Any T, N1, M0, Any G); (Any T, Any N, M1, Any G). N1: Regional lymph node metastasis. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
A term that refers to the staging of soft tissue sarcoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of uterine corpus sarcoma, following the rules of the TNM AJCC v7 classification system.
A well-differentiated adenocarcinoma located in the lung periphery. It resembles colorectal adenocarcinoma with acinar and/or cribriform architecture and papillotubular structures.
A squamous cell lung carcinoma characterized by the absence of keratinization, pearl formation, and intercellular bridges.
A microscopic finding indicating the presence of intercellular bridges connecting adjacent cells in a tissue sample.
Lung adenocarcinoma in situ characterized by the presence of type II pneumocyte and/or Clara cell differentiation. Almost all cases of lung adenocarcinoma in situ are non-mucinous.
A very rare lung adenocarcinoma in situ variant characterized by the presence of tall columnar cells with basal nuclei and abundant cytoplasmic mucin.
A preinvasive bronchial neoplastic lesion affecting the squamous epithelium. It is characterized by the absence of progression of maturation from base to luminal surface, basilar zone expansion with cellular crowding throughout the epithelium, absence of the intermediate zone, and surface flattening confined to the most superficial cells. The nuclear-to-cytoplasmic ratio is often high and variable, the chromatin is coarse and uneven, and mitotic figures are present through full thickness. The cell size may be markedly increased. Anisocytosis and pleomorphism may be present. (Adapted from WHO, 2015)
A finding about one or more characteristics of soft tissue sarcoma of the abdomen and thoracic visceral organs, following the rules of the TNM AJCC v8 classification system. This classification system does not apply to desmoplastic small round cell tumor, epithelioid hemangioendothelioma, inflammatory myofibroblastic tumor, perivascular epithelioid cell tumor (PEComa), solitary fibrous tumor, gastrointestinal stromal tumor (GIST), uterine leiomyosarcoma, and retroperitoneal leiomyosarcoma. This is a new classification system and there is no recommended prognostic stage grouping at this time. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of soft tissue sarcoma of the abdomen and thoracic visceral organs, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of soft tissue sarcoma of the abdomen and thoracic visceral organs, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Soft tissue sarcoma of the abdomen and thoracic visceral organs without distant metastases. (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with distant metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma of the abdomen and thoracic visceral organs, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of soft tissue sarcoma of the abdomen and thoracic visceral organs, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of soft tissue sarcoma of the abdomen and thoracic visceral organs, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Soft tissue sarcoma of the abdomen and thoracic visceral organs in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs, organ confined. (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with tumor extending into tissue beyond organ. (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with tumor invading serosa or visceral peritoneum. (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with tumor extending beyond serosa (mesentery). (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with tumor invading another organ. (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with multifocal involvement. (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with multifocal involvement (two sites). (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with multifocal involvement (three to five sites). (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with multifocal involvement (more than five sites). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma of the abdomen and thoracic visceral organs, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Soft tissue sarcoma of the abdomen and thoracic visceral organs without lymph node involvement or unknown lymph node status. (from AJCC 8th Ed.)
Soft tissue sarcoma of the abdomen and thoracic visceral organs with lymph node involvement. (from AJCC 8th Ed.)
A finding about one or more characteristics of gastrointestinal stromal tumor (GIST), following the rules of the TNM AJCC v8 classification system. This classification system does not apply to pediatric GIST, familial GIST (germline mutant KIT or PDGFRA), or syndromic GIST (no AJCC staging system available). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Gastrointestinal stromal tumor without distant metastasis. (from AJCC 8th Ed.)
Gastrointestinal stromal tumor with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Gastrointestinal stromal tumor in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Gastrointestinal stromal tumor with no evidence of primary tumor. (from AJCC 8th Ed.)
Gastrointestinal stromal tumor measuring 2 cm or less. (from AJCC 8th Ed.)
Gastrointestinal stromal tumor measuring more than 2 cm but not more than 5 cm. (from AJCC 8th Ed.)
Gastrointestinal stromal tumor measuring more than 5 cm but not more than 10 cm. (from AJCC 8th Ed.)
Gastrointestinal stromal tumor measuring more than 10 cm in greatest dimension. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of gastrointestinal stromal tumor, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Gastrointestinal stromal tumor without regional lymph node metastasis or unknown lymph node status. (from AJCC 8th Ed.)
Gastrointestinal stromal tumor with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of gastrointestinal stromal tumor (GIST), following the rules of the TNM AJCC v8 classification system. This staging system does not apply to pediatric GIST, familial GIST (germline mutant KIT or PDGFRA), or syndromic GIST (no AJCC staging system available). (from AJCC 8th Ed.)
A term that refers to the staging of gastric and omental gastrointestinal stromal tumor (GIST), following the rules of the TNM AJCC v8 classification system. (from AJCC 8th Ed.)
A term that refers to the staging of small intestinal, esophageal, colorectal, mesenteric, and peritoneal gastrointestinal stromal tumor (GIST), following the rules of the TNM AJCC v8 classification system. (from AJCC 8th Ed.)
Stage I includes: IA: (T1 or T2, N0, M0, Low Mitotic Rate); IB: (T3, N0, M0, Low Mitotic Rate). T1: Tumor measuring 2 cm or less. T2: Tumor measuring more than 2 cm but not more than 5 cm. T3: Tumor measuring more than 5 cm but not more than 10 cm. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. Low Mitotic Rate: Five or fewer mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage IA includes: T1 or T2, N0, M0, Low Mitotic Rate. T1: Tumor measuring 2 cm or less. T2: Tumor measuring more than 2 cm but not more than 5 cm. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. Low Mitotic Rate: Five or fewer mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage IB includes: T3, N0, M0, Low Mitotic Rate. T3: Tumor measuring more than 5 cm but not more than 10 cm. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. Low Mitotic Rate: Five or fewer mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage II includes: (T1, N0, M0, High Mitotic Rate); (T2, N0, M0, High Mitotic Rate); (T4, N0, M0, Low Mitotic Rate). T1: Tumor measuring 2 cm or less. T2: Tumor measuring more than 2 cm but not more than 5 cm. T4: Tumor measuring more than 10 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. High Mitotic Rate: Over 5 mitoses per 5 square millimeters, or per 50 HPF. Low Mitotic Rate: Five or fewer mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage III includes: IIIA: (T3, N0, M0, High Mitotic Rate); IIIB: (T4, N0, M0, High Mitotic Rate). T3: Tumor measuring more than 5 cm but not more than 10 cm. T4: Tumor measuring more than 10 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. High Mitotic Rate: Over 5 mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage IIIA includes: T3, N0, M0, High Mitotic Rate. T3: Tumor measuring more than 5 cm but not more than 10 cm. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. High Mitotic Rate: Over 5 mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage IIIB includes: T4, N0, M0, High Mitotic Rate. T4: Tumor measuring more than 10 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. High Mitotic Rate: Over 5 mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage IV includes: (Any T, N1, M0, Any Mitotic Rate); (Any T, Any N, M1, Any Mitotic Rate). N1: Regional lymph node metastasis. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody against a tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of SC-006 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action.
Stage I includes: T1 or T2, N0, M0, Low Mitotic Rate. T1: Tumor measuring 2 cm or less. T2: Tumor measuring more than 2 cm but not more than 5 cm. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. Low Mitotic Rate: Five or fewer mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage II includes: T3, N0, M0, Low Mitotic Rate. T3: Tumor measuring more than 5 cm but not more than 10 cm. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. Low Mitotic Rate: Five or fewer mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
A preparation of CD4+ and CD8+ central memory (CM) T-lymphocytes isolated from the peripheral blood of a transplant donor and transduced with a lentiviral vector (LV) (pRRLSIN) expressing a minor H antigen (HA-1(H); HA1(H)) T-cell receptor (TCR) containing the suicide gene inducible caspase 9 (iCasp9 or iC9)-HA1 TCR2-RQR-CD8 transgene (pRRLSIN iC9-HA1 TCR2-RQR-CD8; HA-1 TCR LV), with potential immunostimulating and antineoplastic activities. Upon intravenous administration and after allogeneic hematopoietic stem cell transplantation (HSCT), the CD8+ and CD4+ donor memory T cells-expressing HA1-specific TCR are directed to and induce selective toxicity in HA1-expressing tumor cells. iCasp9 consists of a human FK506 drug-binding domain with an F36V mutation (FKBP12-F36V) linked to human caspase 9. If administration of the T-cells lead to unacceptable side effects, a dimerizing agent rimiducid (AP1903), which binds to the FKBP12-F36V drug-binding domain and activates caspase 9, can be administered; caspase-9 activation results in the apoptosis of the administered TCR-modified T-cells. HA1(H) is a tumor-associated antigen (TAA) that is selectively and highly expressed on leukemic stem cells and blasts, but not in normal non-hematopoietic cells. RQR includes a CD20 epitope, and a CD34 epitope that facilitates both purification and cell tracking of the transduced T-cells with an anti-CD34 monoclonal antibody.
Stage III includes: IIIA: (T1, N0, M0, High Mitotic Rate); (T4, N0, M0, Low Mitotic Rate); IIIB: (T2, N0, M0, High Mitotic Rate); (T3, N0, M0, High Mitotic Rate); (T4, N0, M0, High Mitotic Rate). T1: Tumor measuring 2 cm or less. T2: Tumor measuring more than 2 cm but not more than 5 cm. T3: Tumor measuring more than 5 cm but not more than 10 cm. T4: Tumor measuring more than 10 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. High Mitotic Rate: Over 5 mitoses per 5 square millimeters, or per 50 HPF. Low Mitotic Rate: Five or fewer mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage IIIA includes: (T1, N0, M0, High Mitotic Rate); (T4, N0, M0, Low Mitotic Rate). T1: Tumor measuring 2 cm or less. T4: Tumor measuring more than 10 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. High Mitotic Rate: Over 5 mitoses per 5 square millimeters, or per 50 HPF. Low Mitotic Rate: Five or fewer mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
Stage IIIB includes: (T2, N0, M0, High Mitotic Rate); (T3, N0, M0, High Mitotic Rate); (T4, N0, M0, High Mitotic Rate). T2: Tumor measuring more than 2 cm but not more than 5 cm. T3: Tumor measuring more than 5 cm but not more than 10 cm. T4: Tumor measuring more than 10 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. M0: No distant metastasis. High Mitotic Rate: Over 5 mitoses per 5 square millimeters, or per 50 HPF. (AJCC 8th ed.)
A finding about one or more characteristics of soft tissue sarcoma of the retroperitoneum, following the rules of the TNM AJCC v8 classification system. This classification system applies to common sarcomas in the retroperitoneum. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of soft tissue sarcoma of the retroperitoneum, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of soft tissue sarcoma of the retroperitoneum, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Soft tissue sarcoma of the retroperitoneum without distant metastasis. (from AJCC 8th Ed.)
Soft tissue sarcoma of the retroperitoneum with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma of the retroperitoneum, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of soft tissue sarcoma of the retroperitoneum, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of soft tissue sarcoma of the retroperitoneum, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Soft tissue sarcoma of the retroperitoneum in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Soft tissue sarcoma of the retroperitoneum with no evidence of primary tumor. (from AJCC 8th Ed.)
Soft tissue sarcoma of the retroperitoneum measuring 5 cm or less in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the retroperitoneum measuring more than 5 cm and less than or equal to 10 cm in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the retroperitoneum measuring more than 10 cm and less than or equal to 15 cm in greatest dimension. (from AJCC 8th Ed.)
Soft tissue sarcoma of the retroperitoneum measuring more than 15 cm in greatest dimension. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of soft tissue sarcoma of the retroperitoneum, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Soft tissue sarcoma of the retroperitoneum without regional lymph node metastasis or unknown lymph node status. (from AJCC 8th Ed.)
Soft tissue sarcoma of the retroperitoneum with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of retroperitoneal soft tissue sarcoma, following the rules of the TNM AJCC v8 classification system. This staging system applies to common sarcomas in the retroperitoneum. (from AJCC 8th Ed.)
Stage III includes: IIIA: (T2, N0, M0, G2, G3); IIIB: (T3, T4, N0, M0, G2, G3); (Any T, N1, M0, Any G). T2: Tumor measuring more than 5 cm and less than or equal to 10 cm in greatest dimension. T3: Tumor measuring more than 10 cm and less than or equal to 15 cm in greatest dimension. T4: Tumor measuring more than 15 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. N1: Regional lymph node metastasis. M0: No distant metastasis. G2: Total differentiation, mitotic count and necrosis score of 4 or 5. G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8. (AJCC 8th ed.)
Stage IIIB includes: (T3, T4, N0, M0, G2, G3); (Any T, N1, M0, Any G). T3: Tumor measuring more than 10 cm and less than or equal to 15 cm in greatest dimension. T4: Tumor measuring more than 15 cm in greatest dimension. N0: No regional lymph node metastasis or unknown lymph node status. N1: Regional lymph node metastasis. M0: No distant metastasis. G2: Total differentiation, mitotic count and necrosis score of 4 or 5. G3: Total differentiation, mitotic count and necrosis score of 6, 7, or 8. (AJCC 8th ed.)
Stage IV includes: Any T, Any N, M1, Any G. M1: Distant metastasis. (AJCC 8th ed.)
An orally available and selective inhibitor of the receptor tyrosine kinases (RTKs) Axl (UFO) and Mer, with potential antineoplastic activity. Upon administration, ONO-7475 targets and binds to both Axl and Mer, and prevents their activity. This blocks Axl- and Mer-mediated signal transduction pathways, and inhibits proliferation and migration of Axl- and Mer-overexpressing tumor cells. Axl and Mer, both members of the TAM (Tyro3, Axl and Mer) family of RTKs, are overexpressed by many tumor cell types;. They play key roles in tumor cell proliferation, survival, invasion, angiogenesis and metastasis, and their expression is associated with drug resistance and poor prognosis.
A calcium (Ca2+) release-activated channel (CRAC) inhibitor, with potential antineoplastic activity. Upon administration, RP4010 binds to and inhibits CRACs, thereby preventing the transport of extracellular Ca2+ into the cell and inhibiting the subsequent activation of Ca2+-mediated signaling and transcription of target genes. CRACs, specialized plasma membrane Ca2+ ion channels composed of the plasma membrane based Orai channels and the endoplasmic reticulum (ER) stromal interaction molecules (STIMs), play key roles in calcium homeostasis and are over-activated in a number of cancer cell types. Aberrant activation of CRACs leads to increased cancer cell proliferation.
A finding about one or more characteristics of skin cancer, following the rules of the TNM AJCC v8 classification system. It applies to Merkel cell carcinoma and melanoma of the skin. (from AJCC 8th Ed.)
A finding about one or more characteristics of Merkel cell carcinoma (primary cutaneous neuroendocrine carcinoma), following the rules of the TNM AJCC v8 classification system. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Merkel cell carcinoma without distant metastasis detected on clinical and/or radiologic examination. (from AJCC 8th Ed.)
Merkel cell carcinoma with distant metastasis detected on clinical and/or radiologic examination. (from AJCC 8th Ed.)
Merkel cell carcinoma with metastasis to distant skin, distant subcutaneous tissue, or distant lymph node(s). (from AJCC 8th Ed.)
Merkel cell carcinoma with metastasis to lung. (from AJCC 8th Ed.)
Merkel cell carcinoma with metastasis to all other visceral sites. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Merkel cell carcinoma in which the primary tumor cannot be assessed (e.g., curetted). (from AJCC 8th Ed.)
Merkel cell carcinoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Merkel cell carcinoma with a finding of in situ primary tumor. (from AJCC 8th Ed.)
Merkel cell carcinoma with maximum clinical tumor diameter equal to or less than 2 cm. (from AJCC 8th Ed.)
Merkel cell carcinoma with maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. (from AJCC 8th Ed.)
Merkel cell carcinoma with maximum clinical tumor diameter more than 5 cm. (from AJCC 8th Ed.)
Merkel cell carcinoma with primary tumor invading fascia, muscle, cartilage, or bone. (from AJCC 8th Ed.)
Merkel cell carcinoma in which the lymph nodes cannot be clinically assessed (e.g., previously removed for another reason, or because of body habitus). (from AJCC 8th Ed.)
Merkel cell carcinoma without regional lymph node metastasis detected on clinical and/or radiologic examination. (from AJCC 8th Ed.)
Merkel cell carcinoma with metastasis in regional lymph node(s). (from AJCC 8th Ed.)
Merkel cell carcinoma with in-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) without lymph node metastasis. (from AJCC 8th Ed.)
Merkel cell carcinoma with in-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) with lymph node metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Merkel cell carcinoma with distant metastasis microscopically confirmed. (from AJCC 8th Ed.)
Merkel cell carcinoma with metastasis to distant skin, distant subcutaneous tissue, or distant lymph node(s), microscopically confirmed. (from AJCC 8th Ed.)
Merkel cell carcinoma with metastasis to lung, microscopically confirmed. (from AJCC 8th Ed.)
Merkel cell carcinoma with metastasis to all other distant sites, microscopically confirmed. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Merkel cell carcinoma in which the lymph nodes cannot be assessed (e.g., previously removed for another reason or not removed for pathologic evaluation). (from AJCC 8th Ed.)
Merkel cell carcinoma without regional lymph node metastasis detected on pathologic examination. (from AJCC 8th Ed.)
Merkel cell carcinoma with clinically occult regional lymph node metastasis identified only by sentinel lymph node biopsy. (from AJCC 8th Ed.)
Merkel cell carcinoma with clinically occult regional lymph node metastasis following lymph node dissection. (from AJCC 8th Ed.)
Merkel cell carcinoma with clinically and/or radiologically detected regional lymph node metastasis, microscopically confirmed. (from AJCC 8th Ed.)
A term that refers to the staging of Merkel cell carcinoma (primary cutaneous neuroendocrine carcinoma), following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of Merkel cell carcinoma (primary cutaneous neuroendocrine carcinoma), following the rules of the TNM AJCC v8 classification system.
A term that refers to the clinical staging of Merkel cell carcinoma (primary cutaneous neuroendocrine carcinoma), following the rules of the TNM AJCC v8 classification system.
Stage 0 includes: Tis, N0, M0. Tis: In situ primary tumor. N0: No regional lymph node metastasis detected on clinical and/or radiologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Maximum clinical tumor diameter equal to or less than 2 cm. N0: No regional lymph node metastasis detected on clinical and/or radiologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage II includes: IIA: (T2-3, N0, M0); IIB: (T4, N0, M0). T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. T4: Primary tumor invades fascia, muscle, cartilage, or bone. N0: No regional lymph node metastasis detected on clinical and/or radiologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage IIA includes: T2-3, N0, M0. T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. N0: No regional lymph node metastasis detected on clinical and/or radiologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage IIB includes: T4, N0, M0. T4: Primary tumor invades fascia, muscle, cartilage, or bone. N0: No regional lymph node metastasis detected on clinical and/or radiologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage III includes: T0-4, N1-3, M0. T0: No evidence of primary tumor. T1: Maximum clinical tumor diameter equal to or less than 2 cm. T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. T4: Primary tumor invades fascia, muscle, cartilage, or bone. N1: Metastasis in regional lymph node(s). N2: In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) without lymph node metastasis. N3: In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) with lymph node metastasis. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage IV includes: T0-4, Any N, M1. T0: No evidence of primary tumor. T1: Maximum clinical tumor diameter equal to or less than 2 cm. T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. T4: Primary tumor invades fascia, muscle, cartilage, or bone. M1: Distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
A term that refers to the pathologic staging of Merkel cell carcinoma (primary cutaneous neuroendocrine carcinoma), following the rules of the TNM AJCC v8 classification system.
Stage 0 includes: Tis, N0, M0. Tis: In situ primary tumor. N0: No regional lymph node metastasis detected on pathologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Maximum clinical tumor diameter equal to or less than 2 cm. N0: No regional lymph node metastasis detected on pathologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage II includes: IIA: (T2-3, N0, M0); IIB: (T4, N0, M0). T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. T4: Primary tumor invades fascia, muscle, cartilage, or bone. N0: No regional lymph node metastasis detected on pathologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage IIA includes: T2-3, N0, M0. T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. N0: No regional lymph node metastasis detected on pathologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage IIB includes: T4, N0, M0. T4: Primary tumor invades fascia, muscle, cartilage, or bone. N0: No regional lymph node metastasis detected on pathologic examination. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage III includes: IIIA: (T1-4, N1a(sn) or N1a, M0); (T0, N1b, M0); IIIB: (T1-4, N1b-3, M0). T0: No evidence of primary tumor. T1: Maximum clinical tumor diameter equal to or less than 2 cm. T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. T4: Primary tumor invades fascia, muscle, cartilage, or bone. N1a(sn): Clinically occult regional lymph node metastasis identified only by sentinel lymph node biopsy. N1a: Clinically occult regional lymph node metastasis following lymph node dissection. N1b: Clinically and/or radiologically detected regional lymph node metastasis, microscopically confirmed. N2: In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) without lymph node metastasis. N3: In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) with lymph node metastasis. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage IIIB includes: T1-4, N1b-3, M0. T1: Maximum clinical tumor diameter equal to or less than 2 cm. T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. T4: Primary tumor invades fascia, muscle, cartilage, or bone. N1b: Clinically and/or radiologically detected regional lymph node metastasis, microscopically confirmed. N2: In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) without lymph node metastasis. N3: In-transit metastasis (discontinuous from primary tumor; located between primary tumor and draining regional nodal basin, or distal to the primary tumor) with lymph node metastasis. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Stage IV includes: T0-4, Any N, M1. T0: No evidence of primary tumor. T1: Maximum clinical tumor diameter equal to or less than 2 cm. T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. T4: Primary tumor invades fascia, muscle, cartilage, or bone. M1: Distant metastasis microscopically confirmed. (AJCC 8th ed.)
A finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system. This classification system does not apply to melanoma of the conjunctiva, melanoma of the uvea, mucosal melanoma arising in the head and neck, and mucosal melanoma of the urethra, vagina, rectum, and anus. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Cutaneous melanoma without evidence of distant metastasis. LDH level is not applicable. (from AJCC 8th Ed.)
Cutaneous melanoma with evidence of distant metastasis. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to skin, soft tissue including muscle, and/or nonregional lymph node. LDH level not recorded or unspecified. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to skin, soft tissue including muscle, and/or nonregional lymph node. LDH level not elevated. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to skin, soft tissue including muscle, and/or nonregional lymph node. LDH level elevated. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to lung with or without M1a sites of disease. LDH level not recorded or unspecified. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to lung with or without M1a sites of disease. LDH level not elevated. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to lung with or without M1a sites of disease. LDH level elevated. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to non-CNS visceral sites with or without M1a or M1b sites of disease. LDH level not recorded or unspecified. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to non-CNS visceral sites with or without M1a or M1b sites of disease. LDH level not elevated. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to non-CNS visceral sites with or without M1a or M1b sites of disease. LDH level elevated. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to CNS with or without M1a, M1b, or M1c sites of disease. LDH level not recorded or unspecified. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to CNS with or without M1a, M1b, or M1c sites of disease. LDH level normal. (from AJCC 8th Ed.)
Cutaneous melanoma with distant metastasis to CNS with or without M1a, M1b, or M1c sites of disease. LDH level elevated. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes. The TNM clinical and pathologic regional lymph nodes classifications of cutaneous melanoma are not the same. TNM clinical regional lymph nodes findings are based on clinical/radiographic examination of the regional lymph nodes (clinically detected regional lymph node metastasis). (from AJCC 8th Ed.)
Cutaneous melanoma in which the regional lymph nodes are not assessed (e.g., sentinel lymph node biopsy is not performed, regional lymph nodes were previously removed for another reason). Exception: pathological N category is not required for T1 melanomas, use cN. Presence of in-transit, satellite, and/or microsatellite metastases: No. (from AJCC 8th Ed.)
Cutaneous melanoma without regional lymph node metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: No. (from AJCC 8th Ed.)
Cutaneous melanoma with one tumor-involved node or in-transit satellite, and/or microsatellite metastases with no tumor-involved nodes. (from AJCC 8th Ed.)
Cutaneous melanoma with one clinically detected nodal metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: No. (from AJCC 8th Ed.)
Cutaneous melanoma with no regional lymph node disease. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. (from AJCC 8th Ed.)
Cutaneous melanoma with two or three tumor-involved nodes or in-transit satellite, and/or microsatellite metastases with one tumor-involved node. (from AJCC 8th Ed.)
Cutaneous melanoma with two or three nodal metastases at least one of which was clinically detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. (from AJCC 8th Ed.)
Cutaneous melanoma with one clinically detected metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. (from AJCC 8th Ed.)
Cutaneous melanoma with four or more tumor-involved nodes or in-transit satellite, and/or microsatellite metastases with two or more tumor-involved nodes, or any number of matted nodes without or with in-transit, satellite, and/or microsatellite metastases. (from AJCC 8th Ed.)
Cutaneous melanoma with four or more nodal metastases, at least one of which was clinically detected, or presence of any number of matted nodes. Presence of in-transit, satellite, and/or microsatellite metastases: No. (from AJCC 8th Ed.)
Cutaneous melanoma with two or more clinically detected nodal metastases and/or presence of any number of matted nodes. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Cutaneous melanoma in which the primary tumor thickness cannot be assessed (e.g., diagnosis by curettage). Thickness: Not applicable. Ulceration status: Not applicable. (from AJCC 8th Ed.)
Cutaneous melanoma with no evidence of primary tumor (e.g., unknown primary or completely regressed melanoma). Thickness: Not applicable. Ulceration status: Not applicable. (from AJCC 8th Ed.)
Cutaneous melanoma with a finding of melanoma in situ. Thickness: Not applicable. Ulceration status: Not applicable. (from AJCC 8th Ed.)
Cutaneous melanoma measuring 1.0 mm or less in thickness. Ulceration status: Unknown or unspecified. (from AJCC 8th Ed.)
Cutaneous melanoma measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. (from AJCC 8th Ed.)
Cutaneous melanoma measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Unknown or unspecified. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: With ulceration. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: Unknown or unspecified. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: Without ulceration. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: With ulceration. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 4.0 mm in thickness. Ulceration status: Unknown or unspecified. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 4.0 mm in thickness. Ulceration status: Without ulceration. (from AJCC 8th Ed.)
Cutaneous melanoma measuring more than 4.0 mm in thickness. Ulceration status: With ulceration. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes. The TNM pathologic and clinical regional lymph nodes classifications of cutaneous melanoma are not the same. TNM pathologic findings are based on the microscopic examination of the regional lymph nodes, usually detected by lymphatic mapping and sentinel lymph node biopsy (clinically occult regional lymph node metastasis). (from AJCC 8th Ed.)
Cutaneous melanoma with two or three clinically occult nodal metastases (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. (from AJCC 8th Ed.)
Cutaneous melanoma with one clinically occult nodal metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. (from AJCC 8th Ed.)
Cutaneous melanoma with four or more clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. (from AJCC 8th Ed.)
A score indicating that a patient has 0 or 1 risk factors associated with follicular lymphoma and is considered in the low risk group.
Cutaneous melanoma with two or more clinically occult nodal metastases. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. (from AJCC 8th Ed.)
A score indicating that a patient has 2 risk factors associated with follicular lymphoma and is considered in the intermediate risk group.
A score indicating that a patient has 3 or more risk factors associated with follicular lymphoma and is considered in the high risk group.
A change in the nucleotide sequence of the EPCAM gene that is associated with increased risk of disease.
The reemergence of lymphocyte-rich classical Hodgkin lymphoma after a period of remission.
An aggressive, castration-resistant, histologically distinct, metastatic carcinoma arising from the prostate gland. It is characterized by the presence of a pure population of cytologically bland malignant epithelial cells with moderate to abundant cytoplasm and rare mitotic figures. The prognosis is poor.
A neoplasm arising from the mesothelium that occurs in Oncorhynchus mykiss.
A measurement of the backward flow of blood through the tricuspid valve during right ventricle contraction. It correlates with pulmonary artery systolic pressure at rest and with exercise. A tricuspid regurgitation velocity greater than or equal to 2.5 m/sec on echocardiography is a surrogate marker for pulmonary hypertension in adults with sickle cell disease.
A formulation containing nanoparticles composed of liposomes that are conjugated to scFv antibody fragments directed against the ephrin receptor A2 (EphA2; Ephrin A2) and a proprietary prodrug of docetaxel, a poorly water-soluble, second-generation taxane analog, with potential antineoplastic activity. Upon intravenous administration of the anti-EphA2 antibody-directed liposomal docetaxel prodrug MM-310, the anti-EphA2 moiety selectively targets and binds to cells expressing EphI3:I12A2. Following accumulation of MM-310, docetaxel is slowly released from MM-310 and accumulates at the tumor site due to the unique characteristics of the tumor vasculature. In turn, docetaxel is taken up by tumor cells, where it binds to and stabilizes the beta-subunit of tubulin, thereby stabilizing microtubules and inhibiting microtubule disassembly. This results in cell cycle arrest and the induction of cell death. The cell-surface receptor EphA2, a member of the ephrin family of receptor tyrosine kinases (RTKs) that are involved in mammalian development, is overexpressed by a variety of cancer cell types and plays an important role in tumor growth; its expression is associated with poor prognosis. Compared to free docetaxel, MM-310 increases docetaxel's half-life, and provides enhanced and specific accumulation in EphA2-expressing tumors, thereby increasing docetaxel's efficacy while lowering its systemic toxicity.
An Fc-bearing humanized bispecific dual-affinity re-targeting (DART) protein composed of Fv regions derived from monoclonal antibodies against the immunoregulatory protein B7-homologue 3 (B7-H3, CD276) and the T-cell surface antigen CD3, with potential immunostimulating and antineoplastic activities. Upon administration of the MGD009 DART protein, the anti-B7-H3 component targets and binds to the cell surface antigen B7-H3; at the same time, the anti-CD3 component binds to human CD3. This cross-links the T-cells to B7-H3-expressing tumor cells, activates and redirects endogenous T-cells to kill B7-H3-expressing tumor cells, and inhibits proliferation of B7-H3-expressing tumor cells. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells but is minimally expressed by normal human tissues. B7-H3 is a negative regulator of T-cell activation and its overexpression plays a key role in immuno-evasion, tumor cell invasion and metastasis, and its expression is correlated with poor prognosis.
An engineered, humanized, low fucose monoclonal antibody against mullerian hormone receptor II (Müllerian Inhibiting Substance Receptor II; AMHR2; AMHRII), with potential antineoplastic activity. Upon administration, anti-AMHR2 monoclonal antibody GM102 targets, binds to and inhibits AMHR2 and its downstream signaling pathways. GM102 primarily induces antibody dependent cellular cytotoxicity (ADCC) directed against AMHR2-expressing tumor cells through binding to CD16 (Fc-gammaRIIIa) that is present on immune effector cells. Decreased antibody fucosylation increases its affinity for binding to CD16 and ultimately enhances ADCC. AMHR2 is expressed in a subset of gynecological cancers.
A preparation of cytotoxic T-lymphocytes (CTL) transfected with a chimeric antigen receptor (CAR) specifically recognizing the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1; LMP-1), with potential antineoplastic activity. Upon administration of the LMP1-specific CAR-expressing T lymphocytes to patients with LMP1-positive tumors, the CTLs specifically target and lyse tumor cells expressing LMP1, thereby inhibiting tumor cell proliferation. The tumor-associated antigen (TAA) LMP1 is expressed in various malignancies, including nasopharyngeal cancer and EBV-positive Hodgkin lymphoma.
An antibody-drug conjugate (ADC) composed of patritumab, a monoclonal antibody directed against the human epidermal growth factor receptor HER3 (ErbB3),linked to the topoisomerase I inhibitor DX 8951, a semisynthetic, water-soluble derivative of camptothecin, with potential antineoplastic activity. Upon administration of the anti-HER3 ADC U3 1402, the patritumab moiety targets and binds to HER3. After internalization, DX 8951 inhibits topoisomerase I activity by stabilizing the complex between topoisomerase I and DNA and inhibiting religation of DNA breaks, thereby inhibiting DNA replication and triggering apoptotic cell death. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors.
An oral solution composed of N-acetylcysteine, a synthetic N-acetyl derivative of the endogenous amino acid L-cysteine, and simethicone, a mixture of polydimethylsiloxanes and hydrated silica gel, with mucolytic and antifoaming activities. Upon oral administration of the mucolytic solution, N-acetylcysteine breaks down disulfide bonds in mucoproteins, resulting in liquification of mucus in the upper respiratory tract. Simethicone reduces the surface tension of gas bubbles causing them to coalesce into larger bubbles that can be passed more easily. This increases the passage of mucus and gas bubbles from the upper digestive tract. This may also increase visibility of the gastric mucosa during upper endoscopy.
A term that refers to the staging of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system. This staging system does not apply to melanoma of the conjunctiva, melanoma of the uvea, mucosal melanoma arising in the head and neck, and mucosal melanoma of the urethra, vagina, rectum, and anus. (from AJCC 8th Ed.)
A term that refers to the clinical staging of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system.
Stage 0 includes: Tis, N0, M0. Tis: Melanoma in situ. Thickness: Not applicable. Ulceration status: Not applicable. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage I includes: IA: (T1a, N0, M0); IB: (T1b, N0, M0); (T2a, N0, M0). T1a: Tumor measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. T1b: Tumor measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. T2a: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IA includes: T1a, N0, M0. T1a: Tumor measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IB includes: (T1b, N0, M0); (T2a, N0, M0). T1b: Tumor measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. T2a: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage II includes: IIA: (T2b, N0, M0); (T3a, N0, M0); IIB: (T3b, N0, M0); (T4a, N0, M0); IIC: (T4b, N0, M0). T2b: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: With ulceration. T3a: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: Without ulceration. T3b: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: With ulceration. T4a: Tumor measuring more than 4.0 mm in thickness. Ulceration status: Without ulceration. T4b: Tumor measuring more than 4.0 mm in thickness. Ulceration status: With ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IIA includes: (T2b, N0, M0); (T3a, N0, M0). T2b: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: With ulceration. T3a: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: Without ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IIB includes: (T3b, N0, M0); (T4a, N0, M0). T3b: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: With ulceration. T4a: Tumor measuring more than 4.0 mm in thickness. Ulceration status: Without ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IIC includes: T4b, N0, M0. T4b: Tumor measuring more than 4.0 mm in thickness. Ulceration status: With ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage III includes: Any T, Tis, N1 or More, M0. Tis: Melanoma in situ. Thickness: Not applicable. Ulceration status: Not applicable. N1: One tumor-involved node or in-transit, satellite, and/or microsatellite metastases with no tumor-involved nodes. N2: Two or three tumor-involved nodes or in-transit, satellite, and/or microsatellite metastases with one tumor-involved node. N3: Four or more tumor-involved nodes or in-transit, satellite, and/or microsatellite metastases with two or more tumor-involved nodes, or any number of matted nodes without or with in-transit, satellite, and/or microsatellite metastases. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IV includes: Any T, Any N, M1. M1: Evidence of distant metastasis. (AJCC 8th ed.)
A score indicating that a patient has 0 risk factors associated with follicular lymphoma and is considered in the low risk group.
A score indicating that a patient has 1-2 risk factors associated with follicular lymphoma and is considered in the intermediate risk group.
A score indicating that a patient has 3-5 risk factors associated with follicular lymphoma and is considered in the high risk group.
Stage I includes: IA: (T1a, N0, M0); (T1b, N0, M0); IB: (T2a, N0, M0). T1a: Tumor measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. T1b: Tumor measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. T2a: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IA includes: (T1a, N0, M0); (T1b, N0, M0). T1a: Tumor measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. T1b: Tumor measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IB includes: T2a, N0, M0. T2a: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. N0: No regional lymph node metastasis detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage III includes: IIIA: (T1a/b-T2a, N1a or N2a, M0); IIIB: (T0, N1b, N1c, M0); (T1a/b-T2a, N1b/c or N2b, M0); (T2b/T3a, N1a-N2b, M0); IIIC: (T0, N2b, N2c, N3b or N3c); (T1a-T3a, N2c or N3a/b/c, M0); (T3b/T4a, Any N, N1 or More, M0); (T4b, N1a-N2c, M0); IIID: (T4b, N3a/b/c, M0). T1a: Tumor measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. T1b: Tumor measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. T2a: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. T0: No evidence of primary tumor (e.g., unknown primary or completely regressed melanoma). Thickness: Not applicable. Ulceration status: Not applicable. T2b: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: With ulceration. T3a: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: Without ulceration. T3b: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: With ulceration. T4a: Tumor measuring more than 4.0 mm in thickness. Ulceration status: Without ulceration. T4b: Tumor measuring more than 4.0 mm in thickness. Ulceration status: With ulceration. N1a: One clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. N2a: Two or three clinically occult nodal metastases (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. N1b: One clinically detected nodal metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: No. N1c: No regional lymph node disease. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. N2b: Two or three nodal metastases at least one of which was clinically detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. N2c: One clinically occult nodal metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. N3b: Four or more nodal metastases, at least one of which was clinically detected, or presence of any number of matted nodes. Presence of in-transit, satellite, and/or microsatellite metastases: No. N3c: Two or more clinically occult nodal metastases. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. N3a: Four or more clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IIIA includes: T1a/b-T2a, N1a or N2a, M0. T1a: Tumor measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. T1b: Tumor measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. T2a: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. N1a: One clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. N2a: Two or three clinically occult nodal metastases (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IIIB includes: (T0, N1b, N1c, M0); (T1a/b-T2a, N1b/c or N2b, M0); (T2b/T3a, N1a-N2b, M0). T0: No evidence of primary tumor (e.g., unknown primary or completely regressed melanoma). Thickness: Not applicable. Ulceration status: Not applicable. T1a: Tumor measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. T1b: Tumor measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. T2a: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. T2b: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: With ulceration. T3a: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: Without ulceration. N1b: One clinically detected nodal metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: No. N1c: No regional lymph node disease. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. N2b: Two or three nodal metastases at least one of which was clinically detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. N1a: One clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. N2a: Two or three clinically occult nodal metastases (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IIIC includes: (T0, N2b, N2c, N3b or N3c); (T1a-T3a, N2c or N3a/b/c, M0); (T3b/T4a, Any N, N1 or More, M0); (T4b, N1a-N2c, M0). T0: No evidence of primary tumor (e.g., unknown primary or completely regressed melanoma). Thickness: Not applicable. Ulceration status: Not applicable. T1a: Tumor measuring less than 0.8 mm in thickness. Ulceration status: Without ulceration. T1b: Tumor measuring less than 0.8 mm in thickness with ulceration, or 0.8-1.0 mm with or without ulceration. T2a: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: Without ulceration. T2b: Tumor measuring more than 1.0 and equal to or less than 2.0 mm in thickness. Ulceration status: With ulceration. T3a: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: Without ulceration. T3b: Tumor measuring more than 2.0 and equal to or less than 4.0 mm in thickness. Ulceration status: With ulceration. T4a: Tumor measuring more than 4.0 mm in thickness. Ulceration status: Without ulceration. T4b: Tumor measuring more than 4.0 mm in thickness. Ulceration status: With ulceration. N2b: Two or three nodal metastases at least one of which was clinically detected. Presence of in-transit, satellite, and/or microsatellite metastases: No. N2c: One clinically occult nodal metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. N3b: Four or more nodal metastases, at least one of which was clinically detected, or presence of any number of matted nodes. Presence of in-transit, satellite, and/or microsatellite metastases: No. N3c: Two or more clinically occult nodal metastases. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. N3a: Four or more clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. N1a: One clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. N1b: One clinically detected nodal metastasis. Presence of in-transit, satellite, and/or microsatellite metastases: No. N1c: No regional lymph node disease. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. N2a: Two or three clinically occult nodal metastases (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Breast carcinoma presenting with isolated axillary lymphadenopathy, without clinical or mammographic evidence of breast tumor.
Stage IIID includes: T4b, N3a/b/c, M0. T4b: Tumor measuring more than 4.0 mm in thickness. Ulceration status: With ulceration. N3a: Four or more clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. N3b: Four or more nodal metastases, at least one of which was clinically detected, or presence of any number of matted nodes. Presence of in-transit, satellite, and/or microsatellite metastases: No. N3c: Two or more clinically occult nodal metastases. Presence of in-transit, satellite, and/or microsatellite metastases: Yes. M0: No evidence of distant metastasis. LDH level is not applicable. (AJCC 8th ed.)
Stage IV includes: Any T, Tis, Any N, M1. Tis: Melanoma in situ. Thickness: Not applicable. Ulceration status: Not applicable. M1: Evidence of distant metastasis. (AJCC 8th ed.)
A monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1, PCD-1; PDCD1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-1 monoclonal antibody ABBV-181 targets and binds to PD-1, thereby blocking its binding to the PD-1 ligand, programmed cell death-1 ligand 1 (PD-L1), and preventing the activation of PD-1/PD-L1 downstream signaling pathways. This may restore immune function through the activation of cytotoxic T-lymphocytes (CTLs). PD-1, a transmembrane protein in the immunoglobulin superfamily expressed on activated T-cells, negatively regulates T-cell activation and effector function when activated by its ligand; it plays an important role in tumor evasion from host immunity.
A proprietary formulation comprised of the serine protease inhibitor tranexamic acid (TXA), polyethylene glycol (PEG), electrolytes, and sugar, with potential GI protective activity. After reconstitution in water and upon oral or enteral administration before abdominal surgery, TXA in the protease inhibitor formulation LB1148 targets and inhibits several serine proteases in the gastrointestinal (GI) tract, thereby preventing and protecting the intestinal mucosa against degradation, which preserves gastrointestinal (GI) integrity, function and motility. By inhibiting digestive proteases, the intestinal mucosal barrier is preserved during acute physiologic shock, which may prevent multi-organ failure, postoperative ileus and surgical intra-abdominal adhesions. PEG enhances transport of TXA through the GI tract. The other components provide energy and balance dietary electrolytes, thereby promoting healing of the GI barrier.
A semi-quantitative microscopic finding indicating that less than 5 percent of the nucleated cells in a bone marrow sample are immature mononuclear cells.
Describes a tumor border that is invading the adjacent tissue.
An observation based on clinical, laboratory or molecular evidence, as it relates to conditions occurring in experimental organisms.
A non-neoplastic condition that is relevant to either disease states or models of disease in experimental organisms.
A preparation of allogeneic, frozen, 'off-the-shelf', universal transcription activator-like effector nuclease (TALEN)-engineered, gene-edited T-lymphocytes expressing a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19, and containing a RQR8 transgene, with potential immunostimulating and antineoplastic activities. Using TALEN technology, the T-cell receptor (TCR) alpha chain and CD52 genes are deleted from the CAR19 T-cells. Upon infusion, allogeneic universal CD19-specific CAR-modified T cells (UCART19) specifically target and bind to CD19-expressing tumor cells, thereby selectively lysing CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Deletion of the CD52 gene makes the modified donor T-cells resistant to the anti-CD52 monoclonal antibody alemtuzumab, which is used during lymphodepletion. The knockout of the TCR alpha gene eliminates TCR expression and is intended to abrogate the potential induction of graft-versus-host disease (GvHD) by the donor T-cells. The gene-edited allogeneic, frozen UCART19 have reduced production times and provide off-the-shelf CAR-T cells when compared to autologous CAR-T cells, which use the patient's own cells and are produced on an individual basis. The protein expressed by the RQR8 transgene contains epitopes from CD34 and CD20, which allows tracking of the UCART19 cells with a clinically-approved anti-CD34 antibody. Additionally if the UCART19 cells cause unacceptable side effects, the CD20 portion of the protein permits selective depletion of the UCART19 cells when the anti-CD20 monoclonal antibody rituximab is administered.
A monoclonal antibody against the inhibitory T-cell receptor T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3; TIM3; hepatitis A virus cellular receptor 2; HAVCR2), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the anti-TIM-3 monoclonal antibody LY3321367 binds to TIM-3 expressed on certain T-cells, including tumor infiltrating lymphocytes (TILs). This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which results in a reduction in tumor growth. TIM-3, a transmembrane protein and immune checkpoint receptor, is associated with tumor-mediated immune suppression.
An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody against an unnamed tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of MEDI7247 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action.
A radioimmunoconjugate comprised of a minibody (Mb), an inert antibody fragment against the human CD8-antigen on CD8-positive T-cells, conjugated to the chelator desferrioxamine (Df) and labeled with the radioisotope zirconium Zr 89, with potential positron emission tomography (PET) imaging activity. Upon administration of zirconium Zr 89-Df-IAB22M2C, the Mb moiety specifically targets and binds to the CD8 antigen expressed on T-cells. This enables PET detection of the radioisotope moiety, and may allow the imaging, tracking and quantification of CD8-expressing T-cells. This may detect CD8-positive T-cell distribution and activity, and may help determine the patient's response to cancer immunotherapeutic agents. CD8-positive T-cells play a key role in the eradication of cancer cells. Although the Mb has the same antigen specificity and binding affinity as the full-length antibody, the Mb does not activate or induce the proliferation of CD8-positive T-cells.
Any agent that inhibits isocitrate dehydrogenase (IDH).
A finding indicating that a cellular sample has a functional loss of a protein involved in the DNA mismatch repair process.
An indication that sentinel lymph node mapping was attempted but that it did not identify a sentinel lymph node.
A recently described aggressive subtype of classic lobular breast carcinoma in situ. It is characterized by the presence of neoplastic large cells with irregular nuclei and prominent single or multiple nucleoli.
Anal carcinoma that does not respond to treatment.
Pancreatic neuroendocrine carcinoma that does not respond to treatment.
A preparation of a defined ratio of CD4+ and CD8+ autologous T-lymphocytes transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) containing an anti-CD19 single chain variable fragment (scFv), derived from the CD19-specific murine immunoglobulin (Ig) G1 monoclonal antibody FMC63, fused to the signaling domain of CD28, the zeta chain of the TCR/CD3 complex (CD3-zeta), and a truncated form of the human epidermal growth factor receptor (EGFRt), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the autologous CD19 CAR+ EGFRt + CD4+ and CD8+ T-cells are directed to and induce selective toxicity in CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Devoid of both ligand binding domains and tyrosine kinase activity, the expressed EGFRt both facilitates in vivo detection of the administered, transduced T-cells and can promote elimination of those cells through a cetuximab-induced antibody dependent cellular cytotoxicity (ADCC) response.
A formulation composed of nanoparticles derived from the human papillomavirus (HPV-NPs) and conjugated to the infrared (IR)-activated fluorescent dye IR700 (IR-700), with potential antineoplastic activity. Upon intravitreal injection, the HPV-NPs target and bind to heparan-sulfated proteoglycans (HSPG) expressed by ocular melanoma cells. Upon irradiation with near-IR (NIR) light, the photosensitizer IR700 becomes activated, generates reactive oxygen species (ROS) and selectively damages the melanoma cell membrane, which induces necrosis of the melanoma cells while sparing the surrounding, healthy non-HSPG-expressing tissue, and potentially preserving vision. HSPGs are overexpressed on a variety of cancer cell types.
A point mutation in the ALK gene that encodes an amino acid substitution in the ALK tyrosine kinase receptor protein.
A change in the sequence of one or more genes that are involved in the phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling pathway.
The succinate salt form of FF-10101, a FMS-like tyrosine kinase 3 (FLT3; CD135; STK1; FLK2) inhibitor, with potential antineoplastic activity. Upon administration of FLT3 inhibitor FF-10101 succinate (FF-10101-01), FF-10101 irreversibly binds to and inhibits the activity of FLT3. This inhibits the proliferation of FLT3-expressing cancer cells. FLT3, a class III receptor tyrosine kinase (RTK), is overexpressed or mutated in most B lineage neoplasms and in acute myeloid leukemias.
An inhibitor of induced myeloid leukemia cell differentiation protein (myeloid cell leukemia-1; Mcl-1; Bcl2-L-3), with potential pro-apoptotic and antineoplastic activities. Upon administration, AZD5991 binds to Mcl-1, thereby preventing the binding of Mcl-1 to and inactivation of certain pro-apoptotic proteins, and promoting apoptosis of cells overexpressing Mcl-1. Mcl-1, an anti-apoptotic protein belonging to the Bcl-2 family of proteins, is upregulated in cancer cells and promotes tumor cell survival.
An antibody-drug conjugate (ADC) composed of a proprietary monoclonal antibody against the prolactin receptor (PRLR) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of ABBV-176 targets and binds to PRLR expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the PRLR-expressing tumor cells, through an as of yet unknown mechanism of action. PRLR, a tumor-associated antigen (TAA), is overexpressed by a variety of tumor cell types.
The reemergence of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma after a period of remission.
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma that is resistant to treatment.
The reemergence of extranodal diffuse large B-cell lymphoma after a period of remission.
A mutation in the SMARCA4 gene that either inhibits expression of the SMARCA4 protein or results in the translation of an inactive SMARCA4 protein.
The reemergence of central nervous system lymphoma after a period of remission.
Central nervous system lymphoma that is resistant to treatment.
The reemergence of testicular lymphoma after a period of remission.
Testicular lymphoma that is resistant to treatment.
The reemergence of breast lymphoma after a period of remission.
Breast lymphoma that is resistant to treatment.
The reemergence of intravascular large B-cell lymphoma after a period of remission.
Intravascular large B-cell lymphoma that is resistant to treatment.
The reemergence of primary cutaneous diffuse large B-cell lymphoma, leg type after a period of remission.
Primary cutaneous diffuse large B-cell lymphoma, leg type that is resistant to treatment.
Aberrant activation of an ERBB family member-dependent signaling pathway.
A change in the nucleotide sequence of the ERBB4 gene.
An orally available reversible inhibitor of Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon administration, ARQ 531 non-covalently binds to and inhibits the activity of both the wild-type and the C481S mutated form of BTK, a resistance mutation in the BTK active site in which cysteine is substituted for serine at residue 481. This prevents the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B-cells that overexpress BTK. Compared to other BTK inhibitors, ARQ 531 does not require interaction with the BTK C481 site and inhibits the proliferation of cells harboring the BTK C481S mutation. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed or mutated in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes.
A cytogenetic abnormality that refers to any translocation involving the FGFR2 gene.
A genetic finding indicating the presence of mutations in the cell-free DNA that is present in a peripheral blood sample.
A laboratory test result indicating the presence of an increased level of the tumor-associated antigen (TAA) CA19-9 in a biological sample.
A genetic finding indicating that low expression of the ASS1 gene has been detected in a sample.
An orally bioavailable inhibitor of ataxia telangiectasia mutated kinase (ATM), with potential chemo-/radio-sensitizing and antineoplastic activities. Upon oral administration, M 3541 targets and binds to ATM, thereby inhibiting the kinase activity of ATM and ATM-mediated signaling. This prevents DNA damage checkpoint activation, disrupts DNA damage repair, induces tumor cell apoptosis, and leads to cell death of ATM-overexpressing tumor cells. In addition, M 3541 sensitizes tumor cells to chemo- and radiotherapy. ATM, a serine/threonine protein kinase, is upregulated in a variety of cancer cell types; it is activated in response to DNA damage and plays a key role in DNA-strand repair.
A subjective response indicating that an individual never has or had an erection when they wanted one.
A subjective response indicating that an individual has or had an erection less than half the time when they wanted one.
A subjective response indicating that an individual has or had an erection about half the time when they wanted one.
A subjective response indicating that an individual has or had an erection whenever they wanted one.
A subjective response indicating that an individual did not use any absorbent pads per day.
A subjective response indicating that an individual uses or used one absorbent pad per day.
A subjective response indicating that an individual uses or used two absorbent pads per day.
A subjective response indicating that an individual uses or used three absorbent pads per day.
A subjective response indicating that an individual frequently dribbles urine.
A subjective response indicating that an individual occasionally dribbles urine.
A subjective response indicating that an individual has or had total urinary control.
A molecular abnormality indicating rearrangement of the DUSP22 gene.
A pulmonary nodule with well-defined margins and homogenous soft-tissue attenuation on CT scan examination.
A term that refers to a pure ground-glass pulmonary nodule or a part-solid pulmonary nodule on CT scan examination.
A term that refers to a pulmonary nodule in which there are no completely obscured parenchymal areas by the ground-glass opacity on CT scan examination.
A personalized, polyepitope DNA vaccine composed of a DNA plasmid encoding multiple, highly immunogenic tumor associated antigens (TAAs) that are specifically expressed by a patient's pancreatic cancer cells, including personalized epitopes of the TAA mesothelin, with potential immunostimulatory and antineoplastic activities. Upon intramuscular administration and electroporation of the neoantigen DNA-based pancreatic cancer vaccine, the expressed TAAs induce a specific cytotoxic T-lymphocyte (CTL) immune response against tumor cells expressing the neoantigens.
An orally bioavailable, selective tropomyosin-related-kinase (tyrosine receptor kinase; TRK) inhibitor, with potential antineoplastic activity. Upon oral administration, LOXO-195 specifically targets and binds to TRK, including the fusion proteins containing sequences from neurotrophic tyrosine receptor kinase (NTRK) types 1 (NTRK1), 2 (NTRK2), and 3 (NTRK3). This prevents neurotrophin-TRK interaction and TRK activation, which results in both the induction of cellular apoptosis and the inhibition of cell growth in tumors that overexpress TRK and/or express NTRK fusion proteins. LOXO-195 targets specific point mutations that occur after treatment with and result in acquired resistance to another TRK inhibitor; therefore, LOXO-195 is able to overcome acquired resistance to other TRK inhibitors. TRK, a family of receptor tyrosine kinases (RTKs) activated by neurotrophins, is encoded by NTRK family genes. The expression of either mutated forms of or fusion proteins involving NTRK family members results in uncontrolled TRK signaling and plays an important role in tumor cell growth and survival.
Indicates that a toxicity adverse effect has been experienced by a patient, but it is not severe enough for the patient to discontinue the treatment.
Indicates that a toxicity adverse effect has been experienced by a patient, and it is severe enough for the patient to discontinue the treatment.
Indicates that a toxicity adverse effect has been experienced during endocrine drug treatment.
An inhibitor of Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon administration, CT-1530 binds to and inhibits the activity of BTK. This prevents both the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B-cells that overexpress BTK. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed or mutated in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes.
An orally bioavailable inhibitor of cyclin-dependent kinase (CDK) types 4 (CDK4) and 6 (CDK6), with potential antineoplastic activity. Upon administration, CDK4/6 inhibitor G1T38 selectively inhibits CDK4 and CDK6, which inhibits the phosphorylation of retinoblastoma protein (Rb) early in the G1 phase, prevents CDK-mediated G1-S phase transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of both cell cycle progression from the G1-phase into the S-phase and tumor cell proliferation.
Severe organ dysfunction as assessed by signs, symptoms and laboratory studies, resulting from rapid progression of neoplastic disease. It is indicative of substantial visceral compromise and may serve as an indication for more aggressive therapeutic intervention.
A header term that includes the following prostate carcinoma subtypes determined by gene expression profiling: luminal A prostate carcinoma, luminal B prostate carcinoma, and basal-like prostate carcinoma.
Prostate carcinoma associated with increased androgen receptor expression and signaling (androgen activity pathway), increased luminal markers, and a lower proliferation score than the luminal B and basal-like prostate carcinomas.
Prostate carcinoma associated with increased androgen receptor expression and signaling (androgen activity pathway), increased luminal markers, and a higher proliferation score than the luminal A prostate carcinoma. Patients with luminal B prostate carcinoma have the poorest prognosis but respond better to postoperative androgen deprivation therapy compared to patients with non-luminal B prostate carcinoma.
Prostate carcinoma in which the CD49f signature is increased, the luminal markers and androgen receptor expression and signaling (androgen activity pathway) are not increased, and the proliferation score is higher than the luminal A prostate carcinoma.
A cytogenetic abnormality that involves a translocation between chromosomes 11 and 18.
The reemergence of an abdominal neuroendocrine neoplasm after a period of remission.
An abdominal neuroendocrine neoplasm that does not respond to treatment.
A predominantly diffuse, low-grade follicular lymphoma. It often presents as a large localized inguinal mass, lacks BCL2 rearrangement, and is associated with 1p36 deletion.
A neoplastic lymphoid process characterized by the presence of cyclin D1 positive lymphoid cells, typically in the inner mantle zones of lymphoid tissue follicles, in cases that do not suggest the diagnosis of a mantle cell lymphoma. It is often found incidentally and has a low rate of progression.
A response indicating a very small amount.
A response indicating that an individual required assistance with registering.
A response indicating that an individual required assistance reading questions.
A response indicating that an individual required assistance entering answers.
A response indicating that an individual required assistance submitting a questionnaire.
A response indicating that an individual used their personal smartphone.
A response indicating that an individual used their personal tablet.
A response indicating that an individual used a tablet belonging to a healthcare clinic.
A response indicating that an individual used the smartphone belonging to a friend or family member.
Unprepared colon segment with mucosa not seen due to solid stool that cannot be cleared.
Portion of mucosa of the colon segment seen, but other areas of the colon segment not well seen due to staining, residual stool and/or opaque liquid.
Minor amount of residual staining, small fragments of stool and/or opaque liquid, but mucosa of colon segment seen well.
Entire mucosa of colon segment seen well with no residual staining, small fragments of stool or opaque liquid.
A B-cell lymphoma characterized by the presence of a diffuse proliferation of large, atypical HHV8-positive, EBV-negative neoplastic lymphocytes. Areas of multicentric Castleman disease are not present.
A response indicating that an individual required assistance getting started with an application.
A response indicating that an individual required assistance reading answers.
A response indicating that an individual required assistance reading questions and answers.
A response indicating that an individual used a paper form.
An insertion of the amino acid sequence glycine-valine between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence alanine-serine-valine between the methionine at position 766 and the alanine at position 767 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence asparagine-proline between the proline at position 772 and the histidine at position 773 of the epidermal growth factor receptor protein.
An insertion of the amino acid sequence proline-histidine-valine between the proline at position 772 and the valine at position 774 of the epidermal growth factor receptor protein.
An insertion of six nucleotides, guanine-guanine-cytosine-adenine-cytosine-adenine, between position 2310 and 2311 of the coding sequence of the EGFR gene.
A response indicating than an individual has or had a severe decrease in their food intake.
A response indicating than an individual has or had a moderate decrease in their food intake.
An insertion of the amino acid sequence glycine-threonine between the aspartic acid at position 770 and the asparagine at position 771 of the epidermal growth factor receptor protein.
A response indicating than an individual has or had no decrease in their food intake.
A response indicating than an individual has or had weight loss exceeding 3 kilograms.
A response indicating than an individual has or had weight loss between 1 and 3 kilograms.
An insertion of six nucleotides, cytosine-cytosine-cytosine-adenine-cytosine-guanine, between position 2320 and 2321 of the coding sequence of the EGFR gene.
A response indicating than an individual has or had no weight loss.
A response indicating than an individual is or was bed or chair bound.
A response indicating than an individual is or was able to get out of bed or chair, but did or does not go out.
An insertion of the amino acid sequence alanine-histidine between the histidine at position 773 and the valine at position 774 of the epidermal growth factor receptor protein.
A response indicating than an individual is or was able to go out.
A response indicating than an individual has or had severe dementia or depression.
A response indicating than an individual has or had mild dementia or depression.
A response indicating than an individual has or had no psychological problems.
A response indicating than an individual is not or was not as good as others.
Indicates a body mass index measurement less than 19.
Indicates a body mass index measurement greater than or equal to 19 but below 21.
Indicates a body mass index measurement greater than or equal to 21 but below 23.
Indicates a body mass index measurement greater than or equal to 23.
A finding that indicates the amount of prostate specific antigen in a sample.
A myelodysplastic syndrome in which the blasts constitute more than five percent of the bone marrow cells.
The reemergence of high risk myelodysplastic syndrome after a period of remission.
A group of cells that exhibit some type of cytologic alteration resulting in basophilia, and that are confined to a specific area of the sample.
A score assigned to a biopsy sample indicating the relative amount of cells with glandular differentiation.
Greater than 75% of tumor area shows glandular/tubular structures.
10% to 75% of tumor area shows glandular/tubular structures.
Less than 10% of tumor area shows glandular/tubular structures.
Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size.
Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape.
Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and highly unusual forms.
A score assigned to a biopsy sample to indicate the number of mitotic cells present in a tumor.
A finding of less than or equal to 3 mitoses per mm2 (less than or equal to 7 per 10 hpf).
A finding of greater than or equal to 8 mitoses per mm2 (greater than 15 per 10 hpf).
The dihydrochloride salt form of copanlisib, a phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. Copanlisib inhibits the activation of the PI3K signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.
The hydrochloride salt form of capmatinib, an orally bioavailable inhibitor of the proto-oncogene c-Met (also known as hepatocyte growth factor receptor (HGFR)) with potential antineoplastic activity. Capmatinib selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. This may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis, and tumor angiogenesis.
The cumulative score for the G-8 geriatric assessment, summing the individual scores from the 7 nutritional questions and the age question. The score ranges from 17 (not at all impaired) to 0 (heavily impaired). A score lower or equal to 14 requires comprehensive geriatric assessment.
An allogeneic cell lysate-based vaccine derived from the glioma stem cell line GBM6-AD, which was isolated from the brain tumor of a patient diagnosed with glioblastoma multiforme (GBM), with potential immunostimulatory and antineoplastic activities. Upon subcutaneous administration, the glioma lysate vaccine GBM6-AD exposes the immune system to an undefined amount of glioma-associated antigens (GAAs), and stimulates the immune system to mount a specific anti-tumoral, cytotoxic T-lymphocyte (CTL)-mediated response against the GAA-expressing cells, resulting in glioma cell lysis.
A soft tissue sarcoma that does not respond to treatment.
A nanoparticle-based prodrug formulation consisting of polymeric micelles encapsulating the anthracycline epirubicin, with potential antineoplastic activity. Epirubicin is covalently bound to polyethylene glycol (PEG) polyaspartate block copolymers through an acid-labile hydrazone bond and, upon suspension in an aqueous solution, a micellar structure with an outer hydrophilic PEG shell surrounding the hydrophobic epirubicin is formed. Upon administration of the micellar nanoparticle-encapsulated epirubicin, the nanoparticles are stable in the bloodstream and specifically accumulate in the tumor tissue. Due to the acidic conditions in the tumor and the pH-responsive nature of the micelles, epirubicin is released in the tumor milieu; it then intercalates into DNA and inhibits topoisomerase II, which inhibits DNA replication and interferes with synthesis of both RNA and protein. Compared to the administration of epirubicin alone, this formulation increases the water-solubility of epirubicin and increases its therapeutic effect while decreasing its cardiotoxicity.
A peripheral T-cell lymphoma that arises from a lymph node.
A header term that refers to the staging of plasma cell myeloma according to the Durie/Salmon staging system.
A header term that refers to the staging of plasma cell myeloma according to the International Staging System.
An immunohistochemical finding indicating the presence of neoplastic lymphocytes manifesting a T follicular helper (TFH) phenotype.
A nodal peripheral T-cell non-Hodgkin lymphoma in which the neoplastic lymphocytes manifest a T Follicular Helper (TFH) Phenotype.
A rare anaplastic large cell lymphoma that can develop following breast implants. It has been reported in patients with saline-and silicone-filled implants. It usually presents as an accumulation of seroma fluid between the implant and the surrounding fibrous capsule. The median interval from the time of the implant to the development of lymphoma is approximately 10 years.
A lesion that develops in the breast tissue following breast implant placement.
A variant of lymphomatoid papulosis which mimics primary cutaneous aggressive epidermotropic CD8-positive cytotoxic T-cell lymphoma.
A variant of lymphomatoid papulosis characterized by the presence of atypical lymphocytes which exhibited distinct angioinvasion.
A cytogenetic abnormality indicating the presence of rearrangement of chromosome 6p25.
A variant of lymphomatoid papulosis associated with chromosomal rearrangement of 6p25.
A clonal lymphoproliferative disorder affecting many sites of the gastrointestinal tract. It can be derived from either CD8 or less often CD4 positive T cells. It has an indolent clinical course.
A morphologic finding indicating the presence of a superficial monoclonal T-lymphocytic infiltrate in the gastrointestinal tract.
A cutaneous T-cell lymphoma presenting as an acral (peripheral) lesion. It was originally described as originating in the ear and is usually localized to a single site. It is composed of CD8-positive neoplastic T-lymphocytes. It has an indolent clinical course.
A lesion that arises in a peripheral site (e.g., limbs, fingers, or ears).
An early lesion of post-transplant lymphoproliferative disorder with the morphologic appearance of florid follicular hyperplasia.
A morphologic finding indicating the presence of prominent follicular hyperplasia in a lymph node sample.
A nodular lymphocyte predominant Hodgkin lymphoma that has progressed to a diffuse T-cell-rich pattern.
The assessment of the severity of preductal aortic coarctation.
The assessment of the severity of juxta-ductal aortic coarctation.
The assessment of the severity of postductal aortic coarctation.
The qualitative measurement of the severity of the aortic coarctation.
The longitudinal displacement of a cardiac valve annulus toward the apex of the heart.
The greatest rate of increase in peak pressure during muscle contraction.
The peak velocity of the annular motion during ventricular systole.
The size of a pericardial effusion as assessed at the point of greatest separation between the parietal and visceral pericardia.
The measurement of the maximum separation between the parietal and visceral pericardia.
The cross-sectional diameter of a cardiovascular structure measured along its minor axis at mid ventricular systole.
The cross sectional diameter of a cardiovascular structure measured along its major axis at mid ventricular systole.
An estimation as to the cause of the pathology responsible for the cardiac valve regurgitation.
A fold change based on the concentration of a specific drug expected to produce 50 percent inhibition of population growth or replication of a microbial organism.
A fold change based on the concentration of a specific drug expected to produce 50 percent inhibition of the population growth or replication of a microbial organism; it is a ratio calculated by the EC50 Subject Result divided by the EC50 Reference Control Result.
A fold change based on the concentration of a specific drug expected to produce 50 percent inhibition on the enzymatic activity of a microbial organism; it is a ratio calculated by the current IC50 Subject Result divided by the IC50 Subject Result from the baseline visit.
A fold change based on the concentration of a specific drug expected to produce 50 percent inhibition on the enzymatic activity of a microbial organism; it is a ratio calculated by the IC50 Subject Result divided by the IC50 Reference Control Result.
A central point or locus characterized by hypertrophy and basophilia.
A decrease in the number of cells as compared to a standard or norm.
A decrease in the amount of bone tissue as compared to a standard or norm.
A term that refers to alterations in the dentin matrix. Causes include dentinogenesis imperfecta and hypophosphatemic rickets.
A finding indicating the formation of a dentin niche due to cellular alterations.
A decrease in the amount of dentin as compared to a standard or norm.
Accumulation of a mixed cell population of non-neoplastic mesenchymal cells along endosteal surfaces which may be associated with focal osteoclastic bone resorption and marrow fibroplasia. (INHAND)
A finding indicating that the epiphyseal plate is fully calcified.
An increase in the amount of osteoblastic surface as compared to a standard or norm.
An increase in the amount of unmineralized bone matrix as compared to a standard or norm.
A mass formed in the dental pulp due to local accumulation of a substance.
A decrease in the dimension between the two surfaces, in comparison to a standard or norm.
An increase in the dimension between the two surfaces, in comparison to a standard or norm.
A morphologic finding indicating the presence of a cellular infiltrate associated with fibrosis in a tissue sample.
The formation of an atherosclerotic plaque within the vascular wall.
A morphologic finding indicating the presence of necrosis associated with a cellular infiltrate in a tissue sample.
A finding indicating proliferation of the stromal valvular cells
The numerical value that represents the result of a clinical assessment of muscle strength and function during extension that is based on the Brooke Modified Medical Research Council Manual Muscle Test. (Brooke MH, Griggs RC, Mendell JR, Fenichel GM, et al. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981 May-Jun;4(3):186-97. doi:10.1002/mus.880040304).
The numerical value that represents the result of a clinical assessment of muscle strength and function during plantar flexion that is based on the Brooke Modified Medical Research Council Manual Muscle Test. (Brooke MH, Griggs RC, Mendell JR, Fenichel GM, et al. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981 May-Jun;4(3):186-97. doi:10.1002/mus.880040304).
The numerical value that represents the result of a clinical assessment of muscle strength and function during flexion that is based on the Brooke Modified Medical Research Council Manual Muscle Test. (Brooke MH, Griggs RC, Mendell JR, Fenichel GM, et al. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981 May-Jun;4(3):186-97. doi:10.1002/mus.880040304).
The numerical value that represents the result of a clinical assessment of muscle strength and function during abduction that is based on the Brooke Modified Medical Research Council Manual Muscle Test. (Brooke MH, Griggs RC, Mendell JR, Fenichel GM, et al. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981 May-Jun;4(3):186-97. doi:10.1002/mus.880040304).
The numerical value that represents the result of a clinical assessment of muscle strength and function during lateral rotation that is based on the Brooke Modified Medical Research Council Manual Muscle Test. (Brooke MH, Griggs RC, Mendell JR, Fenichel GM, et al. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981 May-Jun;4(3):186-97. doi:10.1002/mus.880040304).
The numerical value that represents the result of a clinical assessment of muscle strength and function during dorsiflexion that is based on the Brooke Modified Medical Research Council Manual Muscle Test. (Brooke MH, Griggs RC, Mendell JR, Fenichel GM, et al. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981 May-Jun;4(3):186-97. doi:10.1002/mus.880040304).
The numerical value that represents the result of a clinical assessment of muscle strength and function during inversion that is based on the Brooke Modified Medical Research Council Manual Muscle Test. (Brooke MH, Griggs RC, Mendell JR, Fenichel GM, et al. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981 May-Jun;4(3):186-97. doi:10.1002/mus.880040304).
The numerical value that represents the result of a clinical assessment of muscle strength and function during eversion that is based on the Brooke Modified Medical Research Council Manual Muscle Test. (Brooke MH, Griggs RC, Mendell JR, Fenichel GM, et al. Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle Nerve. 1981 May-Jun;4(3):186-97. doi:10.1002/mus.880040304).
The numerical value that represents the result of a clinical assessment of muscle strength and function during extension that is based on the Medical Research Council Manual Muscle Test. (Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45, superseding War Memorandum No. 7. London: Her Majesty's Stationary Office; 1976. doi:10.1016/0022-510X(77)90205-2).
The numerical value that represents the result of a clinical assessment of muscle strength and function during plantar flexion that is based on the Medical Research Council Manual Muscle Test. (Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45, superseding War Memorandum No. 7. London: Her Majesty's Stationary Office; 1976. doi:10.1016/0022-510X(77)90205-2).
The numerical value that represents the result of a clinical assessment of muscle strength and function during flexion that is based on the Medical Research Council Manual Muscle. (Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45, superseding War Memorandum No. 7. London: Her Majesty's Stationary Office; 1976. doi:10.1016/0022-510X(77)90205-2).
The numerical value that represents the result of a clinical assessment of muscle strength and function during lateral rotation that is based on the Medical Research Council Manual Muscle Test. (Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45, superseding War Memorandum No. 7. London: Her Majesty's Stationary Office; 1976. doi:10.1016/0022-510X(77)90205-2).
The numerical value that represents the result of a clinical assessment of muscle strength and function during dorsiflexion that is based on the Medical Research Council Manual Muscle Test. (Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45, superseding War Memorandum No. 7. London: Her Majesty's Stationary Office; 1976. doi:10.1016/0022-510X(77)90205-2).
The numerical value that represents the result of a clinical assessment of muscle strength and function during inversion that is based on the Medical Research Council Manual Muscle Test. (Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45, superseding War Memorandum No. 7. London: Her Majesty's Stationary Office; 1976. doi:10.1016/0022-510X(77)90205-2).
The numerical value that represents the result of a clinical assessment of muscle strength and function during eversion that is based on the Medical Research Council Manual Muscle Test. (Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45, superseding War Memorandum No. 7. London: Her Majesty's Stationary Office; 1976. doi:10.1016/0022-510X(77)90205-2).
An indication that the subject has not been able to meet protocol-defined continuation criteria and will not continue to participate in the clinical trial.
An indication that the subject was randomized but should not have been.
An indication that the subject was randomized but should not have been, and was subsequently given study treatment.
An indication that the subject was randomized but should not have been, and was subsequently not given study treatment.
An indication that a subject has not agreed with, or followed the instructions related to, the non-study device.
An indication that a subject has not agreed with, or followed the instructions related to, the study device.
A measurement of the total number of live birth events at which the gestational age of the neonate is 39 weeks and 0 days through 40 weeks and 6 days.
A measurement of the total number of live birth events at which the gestational age of the neonate is less than 37 weeks and 0 days.
The conditions under which an organ is harvested from a dead donor, including the condition of the donor and the environment.
The state or condition of a subject's microsatellite sequences with respect to the inability of their mismatch repair (MMR) proteins to fix a DNA replication error.
A response indicating that an individual used a tablet belonging to a friend or family member.
A rare nodal Epstein-Barr virus-positive peripheral T-cell lymphoma characterized by the presence of Epstein-Barr virus in the majority of the neoplastic cells.
A morphologic finding indicating the presence of acinar and tubular differentiation in a tissue sample of an epithelial neoplasm.
A molecular abnormality indicating rearrangement of the TP63 gene.
A head and neck squamous cell carcinoma that has spread extensively to other anatomical sites or is no longer responding to treatment.
The total score for myelodysplastic syndrome progression that considers the percentage of blasts in bone marrow (scored on a scale from zero to 2), chromosome abnormalities (scored from zero to 1), and the patient's blood counts (scored as zero or 0.5).
An International Prognostic Scoring System for Myelodysplastic Syndrome risk score of 0, corresponding to low risk.
An International Prognostic Scoring System for Myelodysplastic Syndrome risk score of 0.5 to 1.0, corresponding to intermediate-1 risk.
An International Prognostic Scoring System for Myelodysplastic Syndrome risk score of 1.5-2.0, corresponding to intermediate-2 risk.
A finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to invasive (infiltrating) carcinoma of the breast and ductal carcinoma in situ of the breast. It does not apply to breast sarcoma, phyllodes tumor, and breast lymphoma. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Breast cancer without clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the cM0 category. (from AJCC 8th Ed.)
Breast cancer in which there is no clinical or radiographic evidence of distant metastases in the presence of tumor cells or deposits no larger than 0.2 mm detected microscopically or by molecular techniques in circulating blood, bone marrow, or other nonregional nodal tissue in a patient without symptoms or signs of metastases. (from AJCC 8th Ed.)
Breast cancer with distant metastases detected by clinical and radiographic means and/or histologically proven metastases larger than 0.2 mm. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Breast cancer in which regional lymph nodes cannot be assessed (e.g., previously removed). The cNX category is used sparingly in cases where regional lymph nodes have previously been surgically removed or where there is no documentation of physical examination of the axilla. (from AJCC 8th Ed.)
Breast cancer with no regional lymph node metastases (by imaging or clinical examination). (from AJCC 8th Ed.)
Breast cancer with metastasis to movable ipsilateral level I, II axillary lymph node(s). (from AJCC 8th Ed.)
Breast cancer with micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). cN1mi is rarely used but may be appropriate in cases where sentinel node biopsy is performed before tumor resection, most likely to occur in cases treated with neoadjuvant therapy. (from AJCC 8th Ed.)
Breast cancer with metastases in ipsilateral level I, II axillary lymph nodes that are clinically fixed or matted; or in ipsilateral internal mammary nodes in the absence of axillary lymph node metastases. (from AJCC 8th Ed.)
Breast cancer with metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures. (from AJCC 8th Ed.)
Breast cancer with metastases only in ipsilateral internal mammary nodes in the absence of axillary lymph node metastases. (from AJCC 8th Ed.)
Breast cancer with metastases in ipsilateral infraclavicular (level III axillary) lymph node(s) with or without level I, II axillary lymph node involvement; or in ipsilateral internal mammary lymph node(s) with level I, II axillary lymph node metastases; or metastases in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement. (from AJCC 8th Ed.)
Breast cancer with metastases in ipsilateral infraclavicular lymph node(s). (from AJCC 8th Ed.)
Breast cancer with metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s). (from AJCC 8th Ed.)
Breast cancer with metastases in ipsilateral supraclavicular lymph node(s). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. Lobular carcinoma in situ (LCIS) is a benign entity and is removed from TNM staging in the AJCC Cancer Staging Manual, 8th Edition. (from AJCC 8th Ed.)
Breast cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Breast cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Breast cancer with a finding of ductal carcinoma in situ. Lobular carcinoma in situ (LCIS) is a benign entity and is removed from TNM staging in the AJCC Cancer Staging Manual, 8th Edition. (from AJCC 8th Ed.)
Paget disease of the nipple not associated with invasive carcinoma and/or carcinoma in situ (DCIS) in the underlying breast parenchyma. Carcinomas in the breast parenchyma associated with Paget disease are categorized based on the size and characteristics of the parenchymal disease, although the presence of Paget disease should still be noted. (from AJCC 8th Ed.)
Breast cancer with tumor size 20 mm or less in greatest dimension. (from AJCC 8th Ed.)
Breast cancer with tumor size 1 mm or less in greatest dimension. (from AJCC 8th Ed.)
Breast cancer with tumor size more than 1 mm, but not more than 5 mm in greatest dimension (round any measurement 1.0-1.9 mm to 2 mm). (from AJCC 8th Ed.)
Breast cancer with tumor size more than 5 mm, but not more than 10 mm in greatest dimension. (from AJCC 8th Ed.)
Breast cancer with tumor size more than 10 mm, but not more than 20 mm in greatest dimension. (from AJCC 8th Ed.)
Breast cancer with tumor size more than 20 mm, but not more than 50 mm in greatest dimension. (from AJCC 8th Ed.)
Breast cancer with tumor size more than 50 mm in greatest dimension. (from AJCC 8th Ed.)
Breast cancer with tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4. (from AJCC 8th Ed.)
Breast cancer with extension to the chest wall; invasion or adherence to pectoralis muscle in the absence of invasion of chest wall structures does not qualify as T4. (from AJCC 8th Ed.)
Breast cancer with ulceration and/or ipsilateral macroscopic satellite nodules and/or edema (including peau d'orange) of the skin that does not meet the criteria for inflammatory carcinoma. (from AJCC 8th Ed.)
Breast cancer in which both T4a and T4b are present. (from AJCC 8th Ed.)
Breast cancer meeting the criteria of inflammatory carcinoma. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of breast cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Breast cancer in which regional lymph nodes cannot be assessed (e.g., not removed for pathological study or previously removed). (from AJCC 8th Ed.)
Breast cancer with ITCs only (malignant cell clusters no larger than 0.2 mm) in regional lymph node(s). (from AJCC 8th Ed.)
Breast cancer with positive molecular findings by reverse transcriptase polymerase chain reaction (RT-PCR); no ITCs detected. (from AJCC 8th Ed.)
Breast cancer with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. (from AJCC 8th Ed.)
Breast cancer with micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). (from AJCC 8th Ed.)
Breast cancer with metastases in 1-3 axillary lymph nodes, at least one metastasis larger than 2.0 mm. (from AJCC 8th Ed.)
Breast cancer with metastases in ipsilateral internal mammary sentinel nodes, excluding ITCs. (from AJCC 8th Ed.)
Breast cancer with pN1a and pN1b combined. (from AJCC 8th Ed.)
Breast cancer with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. (from AJCC 8th Ed.)
Breast cancer with metastasis in 4-9 axillary lymph nodes (at least one tumor deposit larger than 2.0 mm). (from AJCC 8th Ed.)
Breast cancer with metastases in clinically detected internal mammary lymph nodes with or without microscopic confirmation; with pathologically negative axillary nodes. (from AJCC 8th Ed.)
Breast cancer with metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes. (from AJCC 8th Ed.)
Breast cancer with metastases in 10 or more axillary lymph nodes (at least one tumor deposit larger than 2.0 mm); or metastases to the infraclavicular (level III axillary) lymph nodes. (from AJCC 8th Ed.)
Breast cancer with pN1a or pN2a in the presence of cN2b (positive internal mammary nodes by imaging); or pN2a in the presence of pN1b. (from AJCC 8th Ed.)
Breast cancer with metastases in ipsilateral supraclavicular lymph nodes. (from AJCC 8th Ed.)
A response indicating that an individual used a smartphone or tablet belonging to a friend or family member.
A response indicating that an individual required assistance with installing the app.
A response indicating that an individual required assistance with logging in.
A term that refers to the staging of breast cancer, following the rules of the TNM AJCC v8 classification system. It applies to invasive (infiltrating) carcinoma of the breast and ductal carcinoma in situ of the breast. It does not apply to breast sarcoma, phyllodes tumor, and breast lymphoma. (from AJCC 8th Ed.)
A term that refers to the staging of breast cancer, following the rules of the TNM AJCC v8 classification system. This staging system should only be used in global regions where biomarker tests are not routinely available. (from AJCC 8th Ed.)
Stage 0 includes: Tis, N0, M0. Tis: Ductal carcinoma in situ. Lobular carcinoma in situ is a benign entity and is removed from TNM staging in the AJCC Cancer Staging Manual, 8th Edition. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage I includes: IA: (T1, N0, M0); IB: (T0, N1mi, M0); (T1, N1mi, M0). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1mi: Tumor with micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IA includes: T1, N0, M0. T1: Tumor measuring 20 mm or less in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IB includes: (T0, N1mi, M0); (T1, N1mi, M0). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. N1mi: Tumor with micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage II includes: IIA: (T0, N1, M0); (T1, N1, M0); (T2, N0, M0); IIB: (T2, N1, M0); (T3, N0, M0). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIA includes: (T0, N1, M0); (T1, N1, M0); (T2, N0, M0). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIB includes: (T2, N1, M0); (T3, N0, M0). T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage III includes: IIIA: (T0, N2, M0); (T1, N2, M0); (T2, N2, M0); (T3, N1, M0); (T3, N2, M0); IIIB: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0); IIIC: (Any T, N3, M0). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. N3: Tumor with metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIIA includes: (T0, N2, M0); (T1, N2, M0); (T2, N2, M0); (T3, N1, M0); (T3, N2, M0). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIIB includes: (T4, N0, M0); (T4, N1, M0); (T4, N2, M0). T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIIC includes: Any T, N3, M0. N3: Tumor with metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastases detected by clinical and radiographic means and/or histologically proven metastases larger than 0.2 mm. (AJCC 8th ed.)
A benign epithelial-stromal neoplasm that arises from the anus and resembles the breast fibroadenoma.
A benign epithelial-stromal neoplasm that arises from the perineum and resembles the breast fibroadenoma.
A benign composite neoplasm that arises from the vulva and is characterized by mixed histopathologic features of papillary hidradenoma (hidradenoma papilliferum) and fibroadenoma.
A proprietary recombinant bispecific T-cell engager (BiTE) antibody composed of two single-chain variable fragments (scFv), one directed against the tumor-associated antigen (TAA) Fc receptor-like protein 5 (FCRH5; CD307; FCRL5; IRTA2; BXMAS1) and one that is directed against the CD3 antigen found on T-lymphocytes, with potential immunostimulating and antineoplastic activities. Upon administration of anti-FCRH5/CD3 BiTE antibody BFCR4350A, the bispecific antibody binds to both the CD3 antigen on cytotoxic T-lymphocytes (CTLs) and FCRH5 found on FCRH5-expressing tumor cells. This activates and crosslinks CTLs with FCRH5-expressing tumor cells, which results in the CTL-mediated cell death of FCRH5-expressing tumor cells. FCRH5, an immune receptor translocation-associated protein/Fc receptor homolog (IRTA/FCRH) family member and a B-cell lineage marker, is overexpressed on myeloma cells.
An antagonist of both human C-C chemokine receptor types 2 (CCR2; CD192) and 5 (CCR5; CD195), with potential immunomodulating and antineoplastic activities. Upon administration, CCR2/CCR5 antagonist BMS-813160 specifically binds and prevents the activation of both CCR2 and CCR5. This inhibits the activation of CCR2/CCR5-mediated signal transduction pathways and may inhibit inflammatory processes, angiogenesis, tumor cell migration, tumor cell proliferation and invasion. The G-protein coupled chemokine receptors CCR2 and CCR5 are expressed on the surface of monocytes and macrophages, and stimulate their migration and infiltration; they play key roles in inflammation and autoimmune disease. CCR2 and CCR5 are overexpressed in certain cancer cell types, and are also involved in angiogenesis, and in tumor cell migration, proliferation and metastasis.
A selective inhibitor of cyclin-dependent kinase 7 (CDK7), with potential antineoplastic activity. Upon administration, SY-1365 binds to and inhibits CDK7, thereby inhibiting CDK7-mediated signal transduction pathways. This inhibits cell growth of CDK7-overexpressing tumor cells. CDK7, a serine/threonine kinase, plays a key role in cell proliferation; CDK7 is overexpressed in a variety of tumor cell types.
A term that refers to the staging of breast cancer, following the rules of the TNM AJCC v8 classification system. This staging system should be used in countries where HER2, ER, and PR biomarker tests are routinely performed for patient care (U.S., Canada, etc.). (from AJCC 8th Ed.)
Stage 0 includes: Tis, N0, M0, G1-3, HER2 Status: Any, ER Status: Any, PR Status: Any. Tis: Ductal carcinoma in situ. Lobular carcinoma in situ is a benign entity and is removed from TNM staging in the AJCC Cancer Staging Manual, 8th Edition. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage I includes: IA: (T1, N0, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (T1, N0, M0, G1-2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T1, N0, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T1, N0, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Any); (T0-1, N1mi, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (T0-1, N1mi, M0, G1-2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T0-1, N1mi, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T0-1, N1mi, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Any); (MultiGene Panel-Oncotype Dx Recurrence Score Less Than 11, T1-2, N0, M0, G1-3, HER2 Status: Negative, ER Status: Positive, PR Status: Any); IB: (T1, N0, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T1, N0, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T1, N0, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T1, N0, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T1, N0, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T1, N0, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T1, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T0-1, N1mi, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1mi, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1mi, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-1, N1mi, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-1, N1mi, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1mi, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-1, N1mi, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T2, N0, M0, G1-3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T2, N0, M0, G1-2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T1, N1, M0, G1-3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T1, N1, M0, G1-2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T2, N1, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T2, N1, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T0-2, N2, M0, G1-2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N1mi: Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IA includes: (T1, N0, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (T1, N0, M0, G1-2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T1, N0, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T1, N0, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Any); (T0-1, N1mi, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (T0-1, N1mi, M0, G1-2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T0-1, N1mi, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T0-1, N1mi, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Any); (MultiGene Panel-Oncotype Dx Recurrence Score Less Than 11, T1-2, N0, M0, G1-3, HER2 Status: Negative, ER Status: Positive, PR Status: Any). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1mi: Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IB includes: (T1, N0, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T1, N0, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T1, N0, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T1, N0, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T1, N0, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T1, N0, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T1, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T0-1, N1mi, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1mi, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1mi, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-1, N1mi, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-1, N1mi, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1mi, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-1, N1mi, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T2, N0, M0, G1-3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T2, N0, M0, G1-2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T1, N1, M0, G1-3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T1, N1, M0, G1-2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T2, N1, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T2, N1, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T0-2, N2, M0, G1-2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N1mi: Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
An inhibitor of protein tyrosine phosphatase (PTP) non-receptor type 11 (SHP2; src homology region 2 domain phosphatase; PTPN11), with potential antineoplastic activity. Upon oral administration, SHP2 inhibitor TNO155 binds to and inhibits SHP2. This prevents SHP2-mediated signaling, inhibits MAPK signaling and prevents growth of SHP2-expressing tumor cells. SHP2, an oncoprotein overexpressed in a variety of cancer cell types, regulates cell survival, differentiation and proliferation through activation of the RAS-RAF-ERK signaling pathway. SHP2 also regulates programmed cell death 1 (PD-1)-mediated signal transduction and is involved in immune checkpoint modulation.
A monoclonal antibody that targets the neonatal crystallizable fragment receptor (FcRn), with potential immunomodulating activity. Upon administration, SYNT001 targets and binds to FcRn at the immunoglobulin G (IgG) binding site, thereby preventing the interaction between FcRn and the serum protein IgG. By preventing FcRn/IgG binding, SYNT001 blocks the FcRn-mediated rescue of IgG, enables IgG degradation and prevents IgG-mediated inflammation. IgG plays a key role in many autoimmune diseases and is an important factor in inflammatory processes.
Lung cancer comprising malignant neoplasms from two or more sites, as determined by clinicoopathological assessment.
Stage II includes: IIA: (T1, N0, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T1, N0, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T1, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T1, N0, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T1, N0, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1mi, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1mi, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1mi, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1mi, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1mi, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G1-2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-1, N1, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T2, N0, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G1-2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T2, N0, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T2, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T0-2, N2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); IIB: (T0-1, N1, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T2, N0, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T2, N0, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T2, N0, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T2, N1, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (T2, N1, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-2, N2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T0-2, N2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N1mi: Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIA includes: (T1, N0, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T1, N0, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T1, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T1, N0, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T1, N0, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1mi, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1mi, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1mi, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1mi, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1mi, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G1-2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-1, N1, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T2, N0, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G1-2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T2, N0, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T2, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T0-2, N2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N1mi: Micrometastases (approximately 200 cells, larger than 0.2 mm, but none larger than 2.0 mm). N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIB includes: (T0-1, N1, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-1, N1, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T2, N0, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T2, N0, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T2, N0, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T2, N1, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (T2, N1, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-2, N2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T0-2, N2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
A finding of multiple pulmonary nodules in which radiologic imaging demonstrates the presence of a dominant lesion.
A finding of multiple pulmonary nodules in which radiologic imaging shows no evidence of a dominant lesion.
Problems associated with the failure to properly and adequately reprocess the device.
Stage III includes: IIIA: (T0-1, N1, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T2, N0, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T2, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T2, N1, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N1, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Negative); (T2, N1, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N1, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T2, N1, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Negative); (T3, N0, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N0, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Negative); (T3, N0, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N0, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T3, N0, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Negative); (T0-2, N2, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G1, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-2, N2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-2, N2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T3, N1-2, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G1, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T3, N1-2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T3, N1-2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (Any T, N3, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); IIIB: (T2, N1, M0, G1-2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T2, N1, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N0, M0, G1-2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T3, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-2, N2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-2, N2, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T3, N1-2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T3, N1-2, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T4, N0-2, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (T4, N0-2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T4, N0-2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T4, N0-2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (Any T, N3, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (Any T, N3, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (Any T, N3, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (Any T, N3, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); IIIC: (T2, N1, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T3, N0, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any ); (T0-2, N2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-2, N2, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T3, N1-2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T3, N1-2, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T4, N0-2, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T4, N0-2, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T4, N0-2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T4, N0-2, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G3, HER2 Status: Negative, ER Status: Any, PR Status: Any); (Any T, N3, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (Any T, N3, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (Any T, N3, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (Any T, N3, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (Any T, N3, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (Any T, N3, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (Any T, N3, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (Any T, N3, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (Any T, N3, M0, G3, HER2 Status: Negative, ER Status: Any, PR Status: Any). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. N3: Tumor with metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIIA includes: (T0-1, N1, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-1, N1, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-1, N1, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T2, N0, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T2, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N0, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T2, N1, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N1, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Negative); (T2, N1, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T2, N1, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T2, N1, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Negative); (T3, N0, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N0, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Negative); (T3, N0, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N0, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T3, N0, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Negative); (T0-2, N2, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G1, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-2, N2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-2, N2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); ( T0-2, N2, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T3, N1-2, M0, G1, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G1, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T3, N1-2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T3, N1-2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (Any T, N3, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Positive). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. N3: Tumor with metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIIB includes: (T2, N1, M0, G1-2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T2, N1, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N0, M0, G1-2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T3, N0, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T0-2, N2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T0-2, N2, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T3, N1-2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Positive); (T3, N1-2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T3, N1-2, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T4, N0-2, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (T4, N0-2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (T4, N0-2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (T4, N0-2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (Any T, N3, M0, G1, HER2 Status: Positive, ER Status: Any, PR Status: Any); (Any T, N3, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Positive); (Any T, N3, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Positive); (Any T, N3, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Positive). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. N3: Tumor with metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IIIC includes: (T2, N1, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T3, N0, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any ); (T0-2, N2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T0-2, N2, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T0-2, N2, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T3, N1-2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Negative); (T3, N1-2, M0, G3, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T3, N1-2, M0, G3, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T4, N0-2, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T4, N0-2, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (T4, N0-2, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (T4, N0-2, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (T4, N0-2, M0, G3, HER2 Status: Negative, ER Status: Any, PR Status: Any); (Any T, N3, M0, G1, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (Any T, N3, M0, G1, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (Any T, N3, M0, G2, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (Any T, N3, M0, G2, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (Any T, N3, M0, G2, HER2 Status: Negative, ER Status: Positive, PR Status: Negative); (Any T, N3, M0, G2, HER2 Status: Negative, ER Status: Negative, PR Status: Any); (Any T, N3, M0, G3, HER2 Status: Positive, ER Status: Positive, PR Status: Negative); (Any T, N3, M0, G3, HER2 Status: Positive, ER Status: Negative, PR Status: Any); (Any T, N3, M0, G3, HER2 Status: Negative, ER Status: Any, PR Status: Any). T0: No evidence of primary tumor. T1: Tumor measuring 20 mm or less in greatest dimension. T2: Tumor measuring more than 20 mm, but not more than 50 mm in greatest dimension. T3: Tumor measuring more than 50 mm in greatest dimension. T4: Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or macroscopic nodules); invasion of the dermis alone does not qualify as T4. N0: No regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. N1: Tumor with micrometastases; or metastases in 1-3 axillary lymph nodes; and/or clinically negative internal mammary nodes with micrometastases or macrometastases by sentinel lymph node biopsy. N2: Tumor with metastases in 4-9 axillary lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the absence of axillary lymph node metastases. N3: Tumor with metastases in 10 or more axillary lymph nodes; or in infraclavicular (level III axillary) lymph nodes; or positive ipsilateral internal mammary lymph nodes by imaging in the presence of one or more positive level I, II axillary lymph nodes; or in more than three axillary lymph nodes and micrometastases or macrometastases by sentinel lymph node biopsy in clinically negative ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M0: No clinical or radiographic evidence of distant metastases. Imaging studies are not required to assign the M0 category. (AJCC 8th ed.)
Stage IV includes: Any T, Any N, M1, G1-3, HER2 Status: Any, ER Status: Any, PR Status: Any. G1: Low combined histologic grade (favorable); SBR score of 3-5 points. G2: Intermediate combined histologic grade (moderately favorable); SBR score: 6-7 points. G3: High combined histologic grade (unfavorable); SBR score of 8-9 points. M1: Distant metastases detected by clinical and radiographic means and/or histologically proven metastases larger than 0.2 mm. (AJCC 8th ed.)
A genetic finding indicating an excess of DNA methylation in the promoter region of the MGMT gene.
A finding about one or more characteristics of female reproductive system cancer, following the rules of the TNM AJCC v8 classification system. The TNM categories have been defined to correspond to the FIGO stages. Some amendments have been made in collaboration with FIGO, and the classifications now published have the approval of FIGO, AJCC, and all other national TNM committees of the Union for International Cancer Control (UICC). (from AJCC 8th Ed.)
A finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to all carcinomas of the vulva. Melanoma of the vulva is staged according to the classification for melanoma of the skin. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Vulvar cancer without evidence of distant metastasis (no pathological M0; use clinical M to complete stage group). (from AJCC 8th Ed.)
Vulvar cancer with distant metastasis (including pelvic lymph node metastasis). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. The definitions of the T categories correspond to the stages accepted by FIGO. (from AJCC 8th Ed.)
Vulvar cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Vulvar cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Vulvar cancer with tumor confined to the vulva and/or perineum. Multifocal lesions should be designated as such. The largest lesion or the lesion with the greatest depth of invasion will be the target lesion identified to address the highest pT stage. Depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. (from AJCC 8th Ed.)
Vulvar cancer with lesion measuring 2 cm or less, confined to the vulva and/or perineum, and with stromal invasion of 1.0 mm or less. (from AJCC 8th Ed.)
Vulvar cancer with lesion measuring more than 2 cm, or any size with stromal invasion of more than 1.0 mm, confined to the vulva and/or perineum. (from AJCC 8th Ed.)
Vulvar cancer with tumor of any size with extension to adjacent perineal structures (lower/distal third of the urethra, lower/distal third of the vagina, anal involvement). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of vulvar cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Vulvar cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Vulvar cancer with isolated tumor cells in regional lymph node(s) no greater than 0.2 mm. (from AJCC 8th Ed.)
Vulvar cancer with regional lymph node metastasis with one or two lymph node metastases each less than 5 mm, or one lymph node metastasis equal to 5 mm. (from AJCC 8th Ed.)
Vulvar cancer with regional lymph node metastasis with three or more lymph node metastases each less than 5 mm, or two or more lymph node metastases equal to 5 mm, or lymph node(s) with extranodal extension. (from AJCC 8th Ed.)
Vulvar cancer with lymph node(s) metastasis with extranodal extension. (from AJCC 8th Ed.)
A term that refers to the staging of vulvar cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to all carcinomas of the vulva. Melanoma of the vulva is staged according to the classification for melanoma of the skin. (AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor confined to the vulva and/or perineum. Multifocal lesions should be designated as such. The largest lesion or the lesion with the greatest depth of invasion will be the target lesion identified to address the highest pT stage. Depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IA includes: T1a, N0, M0. T1a: Lesion measuring 2 cm or less, confined to the vulva and/or perineum, and with stromal invasion of 1.0 mm or less. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB includes: T1b, N0, M0. T1b: Lesion measuring more than 2 cm, or any size with stromal invasion of more than 1.0 mm, confined to the vulva and/or perineum. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Tumor of any size with extension to adjacent perineal structures (lower/distal third of the urethra, lower/distal third of the vagina, anal involvement). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: T1-T2, N1-N2c, M0. T1: Tumor confined to the vulva and/or perineum. Multifocal lesions should be designated as such. The largest lesion or the lesion with the greatest depth of invasion will be the target lesion identified to address the highest pT stage. Depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. T2: Tumor of any size with extension to adjacent perineal structures (lower/distal third of the urethra, lower/distal third of the vagina, anal involvement). N1: Regional lymph node metastasis with one or two lymph node metastases each less than 5 mm, or one lymph node metastasis equal to 5 mm. N2a: Three or more lymph node metastases each less than 5 mm. It includes micrometastasis, N2mi. N2b: Two or more lymph node metastases equal to 5 mm. N2c: Lymph node(s) metastasis with extranodal extension. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA includes: T1-T2, N1, M0. T1: Tumor confined to the vulva and/or perineum. Multifocal lesions should be designated as such. The largest lesion or the lesion with the greatest depth of invasion will be the target lesion identified to address the highest pT stage. Depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. T2: Tumor of any size with extension to adjacent perineal structures (lower/distal third of the urethra, lower/distal third of the vagina, anal involvement). N1: Regional lymph node metastasis with one or two lymph node metastases each less than 5 mm, or one lymph node metastasis equal to 5 mm. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIB includes: T1-T2, N2a, N2b, M0. T1: Tumor confined to the vulva and/or perineum. Multifocal lesions should be designated as such. The largest lesion or the lesion with the greatest depth of invasion will be the target lesion identified to address the highest pT stage. Depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. T2: Tumor of any size with extension to adjacent perineal structures (lower/distal third of the urethra, lower/distal third of the vagina, anal involvement). N2a: Three or more lymph node metastases each less than 5 mm. It includes micrometastasis, N2mi. N2b: Two or more lymph node metastases equal to 5 mm. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIC includes: T1-T2, N2c, M0. T1: Tumor confined to the vulva and/or perineum. Multifocal lesions should be designated as such. The largest lesion or the lesion with the greatest depth of invasion will be the target lesion identified to address the highest pT stage. Depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. T2: Tumor of any size with extension to adjacent perineal structures (lower/distal third of the urethra, lower/distal third of the vagina, anal involvement). N2c: Lymph node(s) metastasis with extranodal extension. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IVA includes: (T1-T2, N3, M0); (T3, Any N, M0). T1: Tumor confined to the vulva and/or perineum. Multifocal lesions should be designated as such. The largest lesion or the lesion with the greatest depth of invasion will be the target lesion identified to address the highest pT stage. Depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. T2: Tumor of any size with extension to adjacent perineal structures (lower/distal third of the urethra, lower/distal third of the vagina, anal involvement). T3: Tumor of any size with extension to any of the following: upper/proximal two-thirds of the urethra, upper/proximal two-thirds of the vagina, bladder mucosa, or rectal mucosa; or fixed to pelvic bone. N3: Fixed or ulcerated regional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis (including pelvic lymph node metastasis). (from AJCC 8th Ed.)
A condition that is relevant to either disease states or models of disease in rats or mice.
A primary cutaneous T-cell lymphoproliferative disorder. It usually presents with a solitary plaque or tumor on the face, neck, or upper trunk. Morphologically, it is composed of small to medium-sized CD4-positive, CD8-negative, and CD30-negative pleomorphic T-lymphocytes. A small number of large pleomorphic T-lymphocytes may also be present. The lymphocytic infiltrate is dermal. Focal epidermotropism and subcutaneous involvement may be present. The clinical behavior is almost always indolent and most patients present with localized disease.
Peeling or delamination of composite materials, including coatings, that occurs when layers are separated as a result of stress or impact and resulting in loss of mechanical toughness.
Problem with an implanted or invasive device moving within the body, or being completely expelled from the body.
Problem associated with deformations that lead to twisting or bending of the device.
Major salivary gland cancer with metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension. (from AJCC 6th and 7th Eds.)
A carcinoma arising from the anal canal and occurring in HIV-positive patients.
A pathologic finding about one or more characteristics of laryngeal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
A term that refers to the clinical staging of esophageal squamous cell carcinoma according to the American Joint Committee on Cancer, 8th edition.
A change in the amino acid residue at position 1171 in the ALK tyrosine kinase receptor protein where isoleucine has been replaced by asparagine.
Problems associated with the device's ability to respond to signals from a system designed to interrogate its status.
A molecular abnormality referring to the loss of at least one copy of the PTCH1 gene.
A finding about one or more characteristics of anal cancer, following the rules of the TNM AJCC v8 classification system. This staging system applies to all carcinomas arising in the anal canal, including carcinomas that arise within anorectal fistulas and those arising in the perianal area (anal margin). High-grade neuroendocrine carcinomas (small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma) are staged using this system. There is no AJCC staging system for anal mucosal melanomas and anal well-differentiated neuroendocrine tumors. (from AJCC 8th Ed.)
Anal cancer with tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder. (from AJCC 8th Ed.)
Small intestine cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Small intestine cancer with metastasis in one or two regional lymph nodes. (from AJCC 8th Ed.)
Stage II includes: IIA: T3, N0, M0; IIB: T4a, N0, M0; IIC: T4b, N0, M0. T3: Tumor invades through the muscularis propria into the subserosa or the mesoappendix. T4a: Tumor invades through the visceral peritoneum, including the acellular mucin or mucinous epithelium involving the serosa of the appendix or serosa of the mesoappendix. T4b: Tumor directly invades or adheres to adjacent organs or structures. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Colorectal cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Acute myeloid leukemia that does not respond to treatment.
Hepatocellular carcinoma with solitary tumor equal to or less than 2 cm. (from AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Solitary tumor larger than 2 cm with vascular invasion, or multiple tumors, none larger than 5 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Intrahepatic bile duct cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of perihilar bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of distal bile duct cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Ampulla of Vater cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Exocrine pancreatic cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
A response indicating that an individual is or was very full of energy, with lots of pep.
A molecular genetic abnormality indicating the presence of a mutation in exon 3 of the KRAS gene.
An extended-release (ER), polymer-based injectable formulation containing the indazole derivative granisetron, a selective serotonin (5-hydroxytryptamine; 5-HT) receptor type 3 (5-HT3) antagonist, with anti-emetic activity. Upon subcutaneous administration, granisetron is released from the polymer in a sustained manner, which is based upon the controlled hydrolysis of the polymers, and selectively binds to and inhibits the activity of the 5-HT3 receptors located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone (CTZ) of the area postrema. By preventing stimulation of 5-HT3 receptors, granisetron is able to suppress chemotherapy-induced nausea and vomiting (CINV). Compared to the injection of granisetron alone, injection of the polymer-based formulation allows for therapeutic levels of granisetron over an extended period of time.
A clinical finding about one or more characteristics of Merkel cell carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Stage IIIA includes: (T1-4, N1a(sn) or N1a, M0); (T0, N1b, M0). T0: No evidence of primary tumor. T1: Maximum clinical tumor diameter equal to or less than 2 cm. T2: Maximum clinical tumor diameter more than 2 cm but equal to or less than 5 cm. T3: Maximum clinical tumor diameter more than 5 cm. T4: Primary tumor invades fascia, muscle, cartilage, or bone. N1a(sn): Clinically occult regional lymph node metastasis identified only by sentinel lymph node biopsy. N1a: Clinically occult regional lymph node metastasis following lymph node dissection. N1b: Clinically and/or radiologically detected regional lymph node metastasis, microscopically confirmed. M0: No distant metastasis detected on clinical and/or radiologic examination. (AJCC 8th ed.)
Cutaneous melanoma with one clinically occult nodal metastasis (i.e., detected by sentinel lymph node biopsy). Presence of in-transit, satellite, and/or microsatellite metastases: No. (from AJCC 8th Ed.)
A transmissible neoplastic disease that occurs in the Tasmanian devil. It is spread by biting and is characterized by tumors on the face and mouth.
A Chinese herbal medicine, with potential immunostimulating and antineoplastic activities. Although the mechanism of action is currently unknown, upon administration, YQ1 may cause an induction of apoptosis and an inhibition of tumor cell proliferation. YQ1 might target cancer stem cells (CSCs).
A term that refers to the pathologic staging of cutaneous melanoma, following the rules of the TNM AJCC v8 classification system.
A change in the nucleotide sequence of the DICER1 gene.
An orally bioavailable inhibitor of the androgen receptor (AR), with potential antineoplastic activity. Upon oral administration, AR inhibitor TAS3681 specifically binds to AR. This prevents AR activation, downregulates AR and prevents AR-mediated signaling. This inhibits cell growth in AR-overexpressing tumor cells. AR is overexpressed in prostate cancers and is involved in proliferation, survival and chemoresistance of tumor cells.
A change in the nucleotide sequence of the ERBB3 gene.
A subjective response indicating that an individual has or had no urinary control.
An insertion of the amino acid sequence asparagine-proline-histidine between the proline at position 772 and the histidine at position 773 of the epidermal growth factor receptor protein.
A response indicating than an individual is or was as good as others.
An increase in the amount of bone tissue as compared to a standard or norm.
The numerical value that represents the result of a clinical assessment of muscle strength and function during abduction that is based on the Medical Research Council Manual Muscle Test. (Medical Research Council. Aids to examination of the peripheral nervous system. Memorandum no. 45, superseding War Memorandum No. 7. London: Her Majesty's Stationary Office; 1976. doi:10.1016/0022-510X(77)90205-2).
An International Prognostic Scoring System for Myelodysplastic Syndrome risk score greater than or equal to 2.5, corresponding to high risk.
Breast cancer in which no regional lymph node metastasis is identified or isolated tumor cell clusters (ITCs) are identified only. (from AJCC 8th Ed.)
An agonistic monoclonal antibody directed against the B-cell surface antigen CD40, with potential antineoplastic activity. Upon administration, ABBV-927 binds to CD40 on a variety of immune cell types. This induces CD40-dependent signaling pathways, triggers the proliferation and activation of antigen-presenting cells (APCs), and activates T-cells. This results in an enhanced cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. CD40, a cell surface receptor and member of the tumor necrosis factor receptor superfamily (TNFRSF), is expressed on various immune cells and plays a key role in the activation of the immune system.
Vulvar cancer with no regional lymph node metastasis. (from AJCC 8th Ed.)
Stage IV includes: T1-T3, N3, M0-M1. T1: Tumor confined to the vulva and/or perineum. Multifocal lesions should be designated as such. The largest lesion or the lesion with the greatest depth of invasion will be the target lesion identified to address the highest pT stage. Depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion. T2: Tumor of any size with extension to adjacent perineal structures (lower/distal third of the urethra, lower/distal third of the vagina, anal involvement). T3: Tumor of any size with extension to any of the following: upper/proximal two-thirds of the urethra, upper/proximal two-thirds of the vagina, bladder mucosa, or rectal mucosa; or fixed to pelvic bone. N3: Fixed or ulcerated regional lymph node metastasis. M0: No distant metastasis. M1: Distant metastasis (including pelvic lymph node metastasis). (from AJCC 8th Ed.)
High risk myelodysplastic syndrome that does not respond to treatment.
A finding of 4-7 mitoses per mm2 (8-14 per 10 hpf).
Mucosal melanoma of the head and neck in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Extranodal diffuse large B-cell lymphoma that is resistant to treatment.
The reemergence of an atypical teratoid/rhabdoid tumor after a period of remission.
Adenocarcinoma arising in the colon of a tamarin.
A tumor arising from histiocytes and dendritic cells and occurring in a mouse.
A non-small cell lung carcinoma without evidence of squamous differentiation.
Mantle cell lymphoma involving the peripheral blood, bone marrow, and often spleen. It usually has an indolent clinical course.
Colorectal neuroendocrine tumor without evidence of distant metastasis. (from AJCC 8th Ed.)
A red-pigmented tumor that occurs in a goldfish.
Pleural malignant mesothelioma with tumor limited to the ipsilateral parietal with or without involvement of visceral pleura, mediastinal pleura, and diaphragmatic pleura. (from AJCC 8th Ed.)
Lung cancer with tumor measuring more than 4 cm but 5 cm or less in greatest dimension. (from AJCC 8th Ed.)
Pelvis cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Soft tissue sarcoma of the trunk and extremities without distant metastasis. (from AJCC 8th Ed.)
Deposits accumulating between the outer retina and the retinal pigment epithelium.
A deviation from the normal level of major histocompatibility complex class II molecules expressed at the cell surface.
An increase above the normal concentration of ribitol in the blood.
A deviation from the normal concentration in the circulation of sex hormone-binding globulin, a circulating glycoprotein that transports testosterone and other steroids in the blood.
Any deviation from the normal quantity of secretion of nasal mucus, a thick viscous liquid produced by the mucous membranes of the nose.
Symmetrical thickening, tightening and induration of the skin of the fingers and the skin proximal to the metacarpophalangeal or metatarsophalangeal joints. These changes can involve the entire limb, face, neck and trunk.
Any structural anomaly of the hollow epithelial tube found on the dorsal side of the vertebrate embryo that develops into the central nervous system (i.e. brain and spinal cord).
Any structural anomaly of the bile-secreting organ that is important for detoxification, for fat, carbohydrate, and protein metabolism, and for glycogen storage.
Any abnormality in the activation of T cells, i.e. the change in morphology and behavior of a mature or immature T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific.
An abnormally increased thickness of a leaflet of the aortic valve.
Any structural anomaly of the aortic valve leaflets.
Any structural anomaly of the pulmonary valve leaflets.
An abnormality in which the abdominal organs are positioned in such a way with respect to each other and the left-right axis as to be not clearly lateralised and thus have neither the usual, or normal (situs solitus), nor the mirror-imaged (situs inversus) arrangements.
An anomalous mirror-imaged arrangement of some bronchial structures. Right isomerism is defined as a subset of heterotaxy where some paired structures on opposite sides of the left-right axis of the body are symmetrical mirror images of each other, and have the morphology of the normal right-sided structures (vice versa for left isomerism).
A type of double aortic arch in which the two branches are of equal size. In most cases of double aortic arch, the right aortic arch is larger and located higher than the left aortic arch.
An abnormal communication between the terminus of a coronary artery, bypassing the myocardial capillary bed and entering the right ventricle.
An abnormal communication between coronary artery and a cardiac chamber.
Reduced level of CD16 on the fibroblast surface as assessed by flow cytometry.
Reduced level of CD59 on the fibroblast surface as assessed by flow cytometry.
Reduced level of CD55 on the fibroblast surface as assessed by flow cytometry.
Reduced level of CD16 on the granulocyte surface as assessed by flow cytometry.
Reduced level of CD59 on the granulocyte surface as assessed by flow cytometry.
Reduced level of CD55 on the granulocyte surface as assessed by flow cytometry.
Reduced level of a protein that is normally present on the granulocyte surface as assessed by flow cytometry.
Reduced level of a protein that is normally present on the fibroblast surface as assessed by flow cytometry.
Reduced level of a protein that is normally present on the cell surface as assessed by flow cytometry.
Any abnormal result of flow cytometry, a method that suspends cells in a stream of fluid and passes them through an electronic detection apparatus in order to assess cell count or measure biomarkers or surface molecules.
Any anomaly of the time interval between the start of the Q wave and the end of the T wave as measured by the electrocardiogram (EKG).
Reduced level of T cell receptor excision circle (TRECs) as measured by the TREC assay. Late in maturation, 70% of thymocytes that will ultimately express alpha/beta-T cell receptors form a circular DNA TREC from the excised TCRdelta gene that lies within the TCRalpha genetic locus. The circles are stable but do not increase following cell division and, therefore, become diluted as T cells proliferate. A quantitative polymerase chain reaction (PCR) reaction across the joint of the circular DNA provides the TREC copy number, a marker of newly-formed, antigenically-nave thymic emigrant T cells. [PMID:22001765]
An elevated level of propionylcarnitine in the circulation. Propionylcarnitine is present in high abundance in the urine of patients with Methylmalonyl-CoA mutase (MUT) deficiency.
Muscle fibers contain one or more vacuoles (membrane-bound cavity) associated with collections of membranes arranged in a whorl-like (spiral or circular) manner.
Presence of complement C3 in the dermoepidermal junction that are dsitributed in a linear pattern. This feature can be appreciated by immunofluorescence microscopy.
Presence of IgG antibodies in the dermoepidermal junction that are dsitributed in a linear pattern. This feature can be appreciated by immunofluorescence microscopy.
Presence of IgA antibodies in the dermoepidermal junction that are dsitributed in a linear pattern. This feature can be appreciated by immunofluorescence microscopy.
Any anomaly of the structure of the acellular zone that is between the dermis and the epidermis and which functions to bind the epidermis to the dermis and to serve as a selective barrier allowing the control of molecular and cellular exchanges between the two compartments.
Anomalous coronary origin whereby the left anterior descending (LAD) and the left circumflex artery (LCX) arise separately. Normally, these arteries arise from a common stem, the left main coronary artery (LMCA).
Increased frequency of thetat wave activity in the electroencephalogram. Theta waves have a frequency of 3.5-7.5 Hertz, and are present in very small amounts in healthy waking adult EEGs. Theta activity is normal in small very amounts in the healthy waking adult EEG in a symmetrical distribution.
An abnormally increased ability to bend (dorsiflex) one's fifth finger. To assess this feature, the examiner requests to proband to extend the elbows,to bend the wrist back so that it forms a ninety degree angle to the forearm, and to extend the fingers. Then, the proband is requested to bend the fifth finger back as far as is possible without discomfort. If the angle of the fifth finger exceeds 90 degrees, this is considered to be abnormal.
Deposits accumulating between the retinal pigment epithelium and Bruch's membrane and that are distributed in multiple foci.
Deposits accumulating between the retinal pigment epithelium and Bruch's membrane and that are distributed in a single focus.
Deposits accumulating between the retinal pigment epithelium and Bruch's membrane.
Deposits accumulating between the outer retina and the retinal pigment epithelium and that are distributed with multiple foci.
Deposits accumulating between the outer retina and the retinal pigment epithelium and that have a focal distribution.
Edema/fluid accumulating within the retinal layers.
An anomaly of collagen fibers of the skin that is said to resemble a cauliflower and can be appreciated by electorn microscopy.
Lack of normal alpha rhythm in the EEG. Alpha rhythm has been defined as a rhythm at 8-13 Hz occurring during wakefulness over the posterior regions of the head, generally with higher voltage over the occipital areas. Amplitude is variable but is mostly below 50 microvolt in adults. It is best seen with eyes closed and under conditions of physical relaxation and relative mental inactivity. It is blocked or attenuated by attention, especially visual and mental effort. One should here note the difference between the terms alpha rhythm and alpha activity: Alpha activity refers to activity in the range of 8-13 Hz and alpha rhythm is the activity of 8-13 Hz with specific characteristics as defined above.
Any anomaly of meiosis, a type of cell division that reduces the number of chromosomes in the parent cell by half and produces four gamete cells.
An abnormally elevated proportion of exhausted T cells (Tex) among circulating T cells. T cell exhaustion is a distinct differentiation state that can be distinguished from naive, effector, and memory T cells. Compared to effector (TE) and memory (TMEM) T cells, exhausted T cells (TEX) display impaired effector functions (e.g., rapid production of effector cytokines, cytotoxicity). TEX have limited proliferative potential, especially compared to some subsets of TMEM and naive T cells.
Fusiform collagen fibers with abnormally long spacing (exceeding 100 nm) between electron-dense bands.
Diagonal earlobe creases run from the lower pole of the external meatus, diagonally backwards to the edge of the lobe at approximately 45 degrees.
A transverse linear fissure (crease) in the lobule of the ear.
Any deviation from the normal range of the hormones produced by the thyroid gland.
A reduction below the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).
An elevation above the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).
A deviation from the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).
An epithelial neoplasm originating in the appendix and often associated with cystic dilation of the appendix due to accumulation of gelatinous material, morphologically referred to as mucoceles.
A poorly differentiated type of gastric carcinoma with a substantial amount of extracellular mucus (over 50% of tumor volume) within the tumor.
A subtype of colorectal carcinoma with mucin lakes.
Mucin-producing and septated cyst-forming epithelial neoplasia of the pancreas with a distinctive ovarian-type stroma.
A vascular malformation located in the lip that is related to vascular endothelial cell hyperplasia.
A vascular malformation located in the lip that is related to abnormal vascular morphogenesis.
A vascular malformation located in the lip that is characterized by direct blood shunting from an artery to a vein due to the absence of a capillary bed. The artery and vein can be directly connected by a fistula or indirectly connected by an abnormal vessel channel termed a nidus.
A vascular malformation located in the lip that is characterized by\nectatic papillary dermal capillaries and postcapillary venules in the upper reticular dermis.
An anomaly of blood vessels located in the lip.
A form of hemolytic anemia that can be triggered by cold temperatures.
Reduced wall motion (contraction) of the apex of the left ventricle. This manifestation can be observed on echocardiography.
A wall motion abnormality observed upon left ventricular contraction that affects a specific region of the left ventricle.
Any functional anomaly of the mitral valve.
Any structural anomaly of the leaflets (also known as cusps) of the mitral valve.
Any structural anomaly of the annulus of the mitral valve. The annulus is a ring composed of fibrous and myocardial tissue and is the structure onto which the cusps of the valve attach.
Any structural anomaly of the cells of the mucosa of the oral cavity in the region of the cheek (buccal mucosa cells).
Fears of rejection by and/or separation from significant others, associated with fears of excessive dependency and complete loss of autonomy.
A stable tendency to experience negative emotions, i.e., a disposition to experience aversive emotional states.
A maladaptive personality trait characterized by moderate or greater impairment in personality (self /interpersonal) functioning.
A structural anomaly of vasa vasorum, which are defined as small blood vessels that supply or drain the walls of larger arteries and veins, delivering nutrients and oxygen as well as removing systemic waste products.
Abnormal reduction in length of a tendon which tends to pull (retract) the attached muscle tissue with shortening of the muscle fibers often accompanied by atrophy and fatty degeneration of the affected muscle tissue.
Any lesion observed on an imaging study of the lung that is associated with increased density (usually showing as increased whiteness in the image).
A gangioleneuroma originating from sympathetic ganglion cells in the abdomen.
Mutliple lesions of the oral mucosa resembling those characteristic of the disease lichen planus. These are symmetric reticular lesions that resemble a white, lacelike network, as well as by papules, plaques, erythematous lesions, and erosions.
Mutliple skin lesions resembling those characteristic of the disease lichen planus. These lesions are violaceous (reddish-purple). shiny, isolated, flat-topped papules and plaques.
An abnormal increase in the amount of subcutaneous fat in the legs.
Hemangioma, a benign tumor of the vascular endothelial cells, located in the perineal region, i.e., the region between the anus and the genitals.
Multiple vesicles distributed in mutiple distinct groups consisting of multiple adjacent vesicles.
Multiple pigmented macules located on the skin of the penis.
An increase in the diameter of the ring (annulus) of the tricuspid valve.
Any structural anomaly of the leaflets (also known as cusps) of the tricuspid valve.
Any structural anomaly of the chordae tendinae of the tricuspid valve. The chordae tendineae connect the papillary muscles to the tricuspid valve.
Any structural anomaly of the annulus of the tricuspid valve. The annulus is a ring composed of fibrous and myocardial tissue and is the structure onto which the cusps of the valve attach.
A deviation from the normal concentration in the circulation of angiostatin, an endogenous angiogenesis inhibitor, which blocks the growth of new blood vessels.
A speech pattern characterized by abnormally elevated variability of the pitch of the voice.
A speech pattern characterized by abnormally reduced or lacking variability of the pitch of the voice.
An anomaly of the expressive patterns of speech that involve intonation, stress pattern, loudness variations, pausing, articulatory force, and rhythm.
Repeated and inappropriate mechanical repetition of actions.
Repetitive use of words, phrases, intonation, or sounds of speech, often of the speechof others.
A reduced level of osteocalcin in the blood.
An elevated level of osteocalcin in the blood.
A deviation from the normal concentration of osteocalcin in the blood circulation.
A reduction from the normal concentration of beta-C-terminal telopeptide of type I collagen in the blood circulation.
A abnormal elevation above the normal concentration of beta-C-terminal telopeptide of type I collagen in the blood circulation.
A deviation from the normal concentration of beta-C-terminal telopeptide of type I collagen in the blood circulation, a marker of the rate of bone turnover.
Any structural anomaly of the cortex of the cerebellum.
Reduced size of the superior frontal portion of the cerebral cortex.
A lesion that is observed following light damage to the macula. Damage to the retinal by exposure to intense visible light, usually the sun. Intense light exposure such as staring at the sun causes fine structural anomalies in the outer segments of the photoreceptors and the retinal pigment epithelium (RPE) cells of the macula. Symptoms usually develop within 1 to 4 h after exposure and include decreased vision, metamorphopsia, micropsia, and central or paracentral scotomas. Fundus examination typically shows a small yellow spot with a surrounding gray zone in the foveolar or parafoveolar area. Spontaneous evolution leads to the improvement of visual acuity.
A decreased concentration of sex-hormone binding protein in the circulation.
An increased concentration of calcitriol in the blood. Calcitriol is also known as 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3.
An increased concentration of calcifediol in the blood. Calcifediol is also known as 25-hydroxycholecalciferol or 25-Hydroxyvitamin D3.
An abnormal reduction in telomere length. Telomeres are non-coding, repetitive sequences of DNA at the ends of the chromosomes of eukaryotic cells which become shorter as cells divide, and when telomere attrition reaches its limit, cell proliferation arrest, senescence, and apoptosis can occur.
Any structural anomaly of a chromosome, which is a thread like molecule consisting of DNA and proteins (chromatin) that contains DNA sequences for genes and other genetic elements in linear order.
An abnormal distribution in the number of CD56 bright NK cells, as measured by flow cytometry. CD56 the adhesion molecule mediating homotypic adhesion, and is used as a functional marker for NK cells.
An increased proportion of mast cells are positive for the cell surface marker CD25 (also called interleukin-2 receptor alpha chain).
A defect or impairment in the series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription.
Any abnormality in the series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with regulation of a downstream cellular process, e.g. transcription.
An impaired immune response mediated by cells expressing specific receptors for antigen produced through a somatic diversification process, and allowing for an enhanced secondary response to subsequent exposures to the same antigen (immunological memory).
Impaired response of CD8 T cells to pathogens. CD8 T cells direct the killing of a target cell through the release of granules containing cytotoxic mediators or through the engagement of death receptors.
Impaired proliferation and expansion of a T cell population following activation by an antigenic stimulus.
An abnormally decreased proportion of CD4-negative, CD8-negative (double negative or DN) alpha-beta regulatory T cells (Tregs) as compared to total number of T cells.
An abnormal proportion of CD4-negative, CD8-negative (double negative or DN) alpha-beta regulatory T cells (Tregs) as compared to total number of T cells.
An abnormally increased proportion of naive T cells relative to the total number of T cells.
An abnormally decreased proportion of naive T cells relative to the total number of T cells.
Any abnormality in the proportion of naive T cells relative to the total number of T cells.
Any abnormality in the relative amount of CD4+ and CD8+ T lymphocytes.
Any abnormality in the proportion of CD8 T cells relative to the total number of T cells.
Any abnormality in the proportion of CD4 T cells relative to the total number of T cells.
An increase above the normal level of major histocompatibility complex class II molecules expressed at the cell surface.
A reduction from the normal level of major histocompatibility complex class II molecules expressed at the cell surface.
The presence of megakaryocytes in the bone marrow whose nuclei are more lobulated than expected for the size of the nucleus.
The presence of abnormally high numbers of multinucleated megakaryocytes in the bone marrow.
The presence of abnormally high numbers of micromegakaryocytes in the bone marrow. Micromegakaryocytes are mononuclear diploid cells, with a nucleus similar in size to that of a myeloblast or promyelocyte with the cell being less than 30 micrometers in diameter.
The presence of megakaryocytes in the bone marrow whose nuclei are less lobulated than expected for the size of the nucleus.
A deficiency in the expression of the CD40 ligand on the surface of activated T-lymphocytes.
Abnormal amount of a protein that is normally present on the cell surface of lymphocytes.
A decreased proliferative response of lymphocytes in vitro or in vivo, when stimulated with an anti-CD3 antibody against the T-cell co-receptor, CD3.
A decreased proliferative response of lymphocytes in vitro or in vivo, when stimulated with mitogens, such as phytohemagglutinin (PHA).
Any abnormality in the multiplication or reproduction of B cells, which results in the expansion of a cell population.
Any abnormality in the multiplication or reproduction of T cells, which results in the expansion of a cell population.
Any abnormality in the multiplication or reproduction of lymphocytes, which results in the expansion of a cell population.
Any abnormality in the multiplication or reproduction of cells, which may result in the expansion of a cell population.
Increased rigidity and reduced mobility of the tongue.
Increased muscle weakness upon exposure to cold temperatures.
Purpura that is flat (non-palpable, not raised).
A solid, raised, plateau-like (flat-topped) lesion greater than 1 cm in diameter that is characterized by hardening (sclerosis) of the affected skin area (related to collagen thickening).
Abnormal difficulty in staying asleep. Affected individuals tend to wake up at night and have difficulty returning to sleep.
Difficulty initiating sleep, that is, increased sleep onset latency.
A non-neoplastic cardiac tumor characterized by calcification and eosinophilic amorphous material in the background of dense collagenous fibrous tissue.
An anomalous configuration of blood vessels that shunts arterial blood directly into veins without passing through the capillaries and that is located in the uterus.
An anomalous configuration of blood vessels that shunts arterial blood directly into veins without passing through the capillaries and that is located in the rectum.
An anomalous configuration of blood vessels that shunts arterial blood directly into veins without passing through the capillaries and that is located in the pelvis.
An anomalous configuration of blood vessels that shunts arterial blood directly into veins without passing through the capillaries and that is located in the jejunum.
A structural anomaly of lysosomes, membrane-enclosed organelles that contain an array of enzymes capable of catabolizing proteins, nucleic acids, carbohydrates, and lipids.
Anomalous staining of dystrophin in cardiomyocytes.
Anomalous staining of plakoglobin in cardiomyocytes. Plakoglobin is a component of desmosomes in cardiomyocytes.
Anomalous staining of Connexin43 in cardiomyocytes. Connexin43 (Cx43) is the primary gap junction protein in the working myocardium. Cx43 exhibits increased localization at the lateral membranes of cardiomyocytes in a variety of heart diseases.
Abnormal localization of mitochondria within the nuclei of cardiomyocytes.
An anomaly of the structure of mitochondria within cardiomyocytes.
Nuclear or cytoplasmic aggregates of stainable substances within cardiomyocytes.
A disruption of the structure of the sarcomeres of cardiomyocytes. The sarcomere is the repeating unit between two Z lines comprised largely of myosin and action that mediates contractility, and normally sarcomeres are aligned with the long axis of cells, with the Z bands being in register throughout the length of the cardiac myocytes.
Deterioration of cardiomyocyte charyacterized by abnormal features sich as loss of myotilaments, occurrence of cellular sequestration, decreased mitochondrial sizes and cellular debris.
Any structural anomaly of cardiomyocytes, which are terminally differentiated muscle cells in the heart that are interconnected end to end by gap junctions, which allows coordinated contraction of heart tissue.
An increase in the number of immune cells in myocardial tissue concentrated in the spaces surrounding blood vessels.
A type of myocardial fibrosis characterized by excessive diffuse collagen accumulation concentrated in interstitial spaces.
A type of myocardial fibrosis characterized by excessive diffuse collagen accumulation concentrated in perivascular spaces.
A type of cardiac amyloidosis related to deposition of transthyretin (TTR), which is indentified by immunohistochemical staining.
A type of cardiac amyloidosis related to deposition of an immunoglobulin light chain. The current gold standard of amyloid typing is to determine the precursor protein using laser microdissection mass spectrometry.
The presence of multiple granulomata (small nodular inflammatory lesions containing grouped mononuclear phagocytes) in the myocardium.
The presence of extremely large cells with multiple nuclei. The so-called giant cells are thought to be of macrophage origin.
An increase in the number of eosinophils in myocardial tissue.
An increase in the number of lymphocytes in myocardial tissue.
An increase in the number of immune cells in myocardial tissue (which can be assumed to have migrated into the myocardium).
An abnormal increase in the number of mitochondria per cardiac myocyte.
Presence of an increased amount of fat tissue withina cardiac ventricle with corresponding reduction of muscle tissue.
A structural anomaly of the muscle layer of the heart wall of a cardiac ventricle.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in the external carotid artery.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in abdominal aorta.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in the middle cerebral artery.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in the basilar artery.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in the vertebral artery.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in the internal carotid artery.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall in an artery that is located within the skull (intracranial).
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall of the tibial artery.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall of the iliac artery.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall of the femoral artery.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall of the leg.
An accumulation of calcium and phosphate in arteries with mineral deposits in the intimal or medial layer of the vessel wall.
A deviation from the normal concentration of properdin in the blood.
An abnormal increase in magnitude of the pressure in the left atrium.
Abnormal increase in size of the coronary sinus.
An abnormal increase in the thickness of the atrial septum.
Underdeveloped, small right heart atrium.
Ichthyosis follicularis is characterized by widespread non inflammatory thorn-like follicular projections. Dyskeratotic papules are most pronounced over the extensor extremities and scalp and are symmetrically distributed.
The presence of verrucous, cobblestone-like papules and nodules in a region of skin that is said to have an appearance like that of cobblestones.
Any structural anomaly in the areas surrounding the hair follicles.
The presence of tufts of 8-15 hairs that appear to emerge from a single follicular orifice.
A lateral deviation of the nail plate of the great toe along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges.
An abnormally high amount of luteinizing hormone (LH) is released upon gonadotropin-releasing hormine stimulation test.
An abnormal response to the gonadotropin-releasing hormone (GnRH) stimulation test. This test typically involves intravenous administration of GnRH followed by repeated blood sampling at various time points to measure the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
Any structural anomaly of the thoracic duct.
Accumulation of lipids and inflammatory cells along the inner walls of the pulmonary artery.
The pulsation of the posterior tibial artery behind the internal malleolus, or of the dorsalis pedis artery,cannot be detected on physical examination.
Decreased or impaired upregulation of CD25 on T cells after activation via the T cell receptor (TCR).
Any abnormality in the upregulation of CD25 on T cells after activation via the T cell receptor (TCR). CD25 is the alpha chain of the IL2 receptor. Ligation of the T cell antigen receptor leads to the induction of CD25 expression.
Reduced or impaired upregulation of CD69 on T cells after activation via the T cell receptor (TCR).
Any abnormality in the upregulation of CD69 on T cells after activation via the T cell receptor (TCR). Upregulation of CD69 is one of the earliest and most sensitive measures of antigen recognition in the periphery, and transient expression of CD69 is associated with positive selection in the thymus.
Any structural anomaly of the podocyte, which is a highly specialized cell of the Bowman capsule and which forms multiple interdigitating foot processes. Podocytes are interconnected by slit diaphragms and cover the exterior basement membrane surface of the glomerular capillary.
A structural anomaly of the double-walled capsule (Bowman capsule) that opens into a renal tubule.
Any anomolous structure of the renal corpuscle, which is the initial component of the nephron that filters blood. The renal corpuscle consists of a knot of capillaries (glomerulus) that is surrounded by a double-walled capsule (Bowman capsule) that opens into a renal tubule.
A short, dysplastic tibia with a triangular shape. Instead of the normal shaft configuration of the tibia, the tibia forms a triangle with the longest side corresponding to the proximal-distal dimension, and the apex of the triangle diected laterally (See Figure 2 of PMID:18616733).
An arteriovenous malformation is a disruption of the normal vascular pattern in which arteries or arterioles connect directly to the venous collection system, bypassing any capillary bed. This term refers to an arteriovenous malformation located in the maxilla.
An arteriovenous malformation is a disruption of the normal vascular pattern in which arteries or arterioles connect directly to the venous collection system, bypassing any capillary bed. This term refers to an arteriovenous malformation located in the optic nerve.
An arteriovenous malformation is a disruption of the normal vascular pattern in which arteries or arterioles connect directly to the venous collection system, bypassing any capillary bed. This term refers to an arteriovenous malformation located in the hypothalamus.
An arteriovenous malformation is a disruption of the normal vascular pattern in which arteries or arterioles connect directly to the venous collection system, bypassing any capillary bed. This term refers to an arteriovenous malformation located in the thalamus.
Origin of the left subclavian artery from an anomaloous anatomical location.
Abnormally increased caliber of the left subclavian artery.
A reduction in the amount of very-low-density lipoprotein cholesterol in the blood.
Reduced plasma concentrations of chylomicrons, the large lipid droplet (up to 100 mm in diameter) of reprocessed lipid synthesized in epithelial cells of the small intestine and containing triacylglycerols, cholesterol esters, and several apolipoproteins.
A type of choroidal neovascularization in which the area of neovascularization overlaps with the center of the fovea.
A type of choroidal neovascularization in which the nearest edge of the area of neovascularization is located 1 to 199 micrometers from the center of the fovea.
A type of choroidal neovascularization in which the nearest edge of the area of neovascularization is located 200 to 1500 micrometers from the center of the fovea.
A histological alteration of muscle fibers that resembles a necklace (necklace fibers). A substantial proportion of fibers (4-20% in PMID:19084976) show internalized nuclei aligned in a basophilic ring (necklace) at 3 micrometers beneath the sarcolemma. Ultrastructurally, such necklaces consist of myofibrils of smaller diameter, in oblique orientation, surrounded by mitochondria, sarcoplasmic reticulum and glycogen granules.
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells). [PMID:22938878]
Collection of neutrophils in the dermis.
Collection of neutrophils in the epidermis.
A predominantly neutrophilic infiltrate of the dermis and or epidermis (i.e., a large number of neutrophils inferred to have migrated into the skin).
Breadth of the incisura from the anterior to posterior border greater than that observed in the average population.
Width of the incisura from the anterior to posterior border less than that observed in the average population.
The length of the incisura from the upper to lower border is less than that observed in the average population.
The length of the incisura from the upper to lower border is greater than that observed in the average population.
An abnormal shape of the incisura, defined as the narrowed downward continuation of the conchal space bounded anteriorly by the borders of the tragus, posteriorly by the antitragus, and along its lower lateral margins and inferior boundary by the connection between the first two. The upper boundary is a somewhat arbitrary line crossing from the apices of the antitragus and the tragus.
A teratoma arising in the nasopharyngeal region.
Hyperplasia of the islets of Langerhans with a generalized distribution.
Hyperplasia of the islets of Langerhans that affects only certain regions of the pancreas and not others.
An elevated concentration of thyroxine-binding globulin (TBG) in the blood.
A decreased amount of uptake on the radioactive iodine uptake (RAIU) test, which utilizes a radioisotope of iodine to measure how much iodine the thyroid gland absorbs from the blood. The radioactive marker is measured 4-6 hours and in some cases also 24 hours afteradministration of the radioactive marker.
An elevated concentration of progesterone in the blood.
A reduced concentration of dehydroepiandrosterone-sulfate in the blood.
An increased level of 17-hydroxyprogesterone in the blood. 17-hydroxyprogesterone is an intermediate steroid in the adrenal biosynthetic pathway from cholesterol to cortisol and is the substrate for steroid 21-hydroxylase.
An elevated concentration of circulating cholesterol esters, which are fatty acid esters of cholesterol and make up about two-thirds of total plasma cholesterol.
A deviation from the normal concentration of hyaluronic acid in the blood.
Reduction in the activity of lipoprotein lipase in the blood.
An increased concentration of circulating alpha polypeptide of glycoprotein hormones (Entrez Gene 1081). This alpha subunit is common to luteinizing hormone (LH) , follicle stimulating hormone (FSH) , thyroid stimulating hormone (TSH) and human chorionic gonadotropin (hCG), which are glycoprotein hormones composed of an identical alpha subunit together with a beta subunit that confers biological specificity. The alpha subunit is used as a marker for tumors that produce these hormones.
Abnormally bright T2 signal from the striatum on brain magnetic resonance imaging.
Reduction in the activity of lysosomal acid lipase (LAL) in the blood. Lysosomal lipase activity is measured. LAL hydrolyzes cholesteryl esters derived from cell internalization of plasma lipoproteins.
A type of urinary cast that contain bacteria. Bacterial casts can be difficult to identify and can be distinguished from other types of casts using phase contrast microscopy. Bacterial casts are diagnostic of acute pyelonephritis or intrinsic renal infection.
A type of urinary cast composed of a proteinaceous matrix without a substantial number of cells.
A type of cellular urinary cast componsed of renal tubular epithelial cells.
Reduced thickness of the outer, dense layer of the myocardium.
An increased number and denisty of the trabeculae in the apex (tip) of the left ventricle.
An increased denisty (number and tightness) of the muscular columns which project from the inner surface of the left ventricles of the heart (cardiac trabeculae, trabeculae carneae).
Any structural anomaly of the muscular columns which project from the inner surface of the right ventricle of the heart (cardiac trabeculae, trabeculae carneae).
Any structural anomaly of the muscular columns which project from the inner surface of the left ventricle of the heart (cardiac trabeculae, trabeculae carneae).
Numerous lymphocytes surrounding blood vessels in the deep part of the dermis.
Numerous lymphocytes surrounding blood vessels in the superfical part of the dermis.
Any anomaly of the function of the breast.
Any anomaly of the structure of the breast.
Telangiectasia (small dilated blood vessels) located near to the fingernails or toenails.
Subcutaneous bleeding with a diamter greater than 1 cm (ecchymosis). The bleeding does not extend into the tarsal plate (the comparatively thick, elongated plates of dense connective tissue within the eyelid) due to an anatomic structure called the orbital septum, which limits extravasation of blood beyond the tarsal plate.
Multiple red/purple spots on the skin that surrounds the eyes that do not blanch (whiten) upon pressure. Purpura is caused by subcutaneous bleeding.
Abnormal decussation of the visual pathways, typically identified using visual evoked potentials (VEP) (asymmetrical distribution of the VEP over the posterior scalp).
An eklevation over the normal range of the average amount of hemoglobin per red blood cell (27 to 31 picograms/cell).
Any structural abnormality of the coronary arteries. [HPO:probinson]
Peripheral arterial stenosis with onset before the age of 50 years. []
Syringomyelia (Greek: 'syrinx,' pipe, and 'myelos,' marrow) is a tubular cavity in the spinal cord. It can occur sporadically in association with spinal cord tumors, inflammatory arachnoiditis, or posttraumatically. It is rarely idiopathic (less than 1% of cases). The vast majority of cases of syringomyelia are cervical, noncommunicating, and associated with an abnormality at the foramen magnum, particularly the Chiari malformation type I (CM1; 118420), as well as basilar impression (109500) and Dandy-Walker malformation (220200) (Speer et al., 2003; Levine, 2004); these cases have shown familial segregation. The form of syringomyelia discussed here is 'noncommunicating' with the fourth ventricle, but may communicate with the subarachnoid space. In contrast, 'communicating' syringomyelia, or 'hydromelia,' opens rostrally into the fourth ventricle and almost always occurs in children with hydrocephalus, Chiari malformation type II (CM2; 207950), and spina bifida (see 182940) (Levine, 2004).
Complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy is characterized by abdominal pain and diarrhea, primary intestinal lymphangiectasia, hypoproteinemic edema, and malabsorption. Some patients also exhibit bowel inflammation, recurrent infections associated with hypogammaglobulinemia, and/or angiopathic thromboembolic disease. Patient T lymphocytes show increased complement activation, causing surface deposition of complement and generating soluble C5a (Ozen et al., 2017).
MISSBC is an autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly, early-onset seizures, and severely delayed or even absent psychomotor development with profound intellectual disability and spasticity or dystonia. Brain imaging shows midbrain dysplasia and intracerebral calcifications (summary by Aran et al., 2016).
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities of the brain, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
The Houge type of X-linked syndromic mental retardation is characterized by delayed development, intellectual disability, speech and language delay, and early-onset seizures. EEG tends to show continuous spike-wave activity or centrotemporal spikes. Some patients may have remission of seizures by adolescence. Carrier females may be mildly affected (summary by Damiano et al., 2017).
X-linked myopia-26 is characterized by female-limited early-onset high myopia. The fundus of affected individuals shows a tigroid appearance, and there is a temporal crescent of the optic nerve head (Xiao et al., 2016). For a discussion of genetic heterogeneity of myopia, see 160700.
Both familial and sporadic pituitary adenomas have been found to be caused by germline mutation in the CDH23 gene. Familial pituitary adenoma types include growth hormone (GH)-secreting and nonfunctional tumors. Sporadic pituitary adenoma types include GH-secreting, nonfunctional, prolactin (PRL)-secreting, adrenocorticotropin (ACTH)-secreting, thyroid-stimulating hormone (TSH)-secreting, and plurihormonal (GH and TSH) tumors. For a general description and a discussion of genetic heterogeneity of pituitary adenomas, see PITA1 (102200).
NPHS14 is an autosomal recessive syndromic form of steroid-resistant nephrotic syndrome with multisystemic manifestations. Most affected individuals present in infancy or early childhood with progressive renal dysfunction associated with focal segmental glomerulosclerosis (FSGS) and resulting in end-stage renal disease within a few years. Other infants present with primary adrenal insufficiency. Some patients present in utero with fetal hydrops and fetal demise. Additional features of the disorder can include ichthyosis, acanthosis, adrenal insufficiency, immunodeficiency, and neurologic defects (summary by Prasad et al., 2017 and Lovric et al., 2017). For a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Spermatogenic failure-18 is a form of male infertility caused by multiple morphologic abnormalities of the sperm flagella (Ben Khelifa et al., 2014). For a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Spermatogenic failure-19 is characterized by multiple morphologic abnormalities of the flagella (MMAF), including absent, short, coiled, bent, and irregular-caliber flagella (Tang et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Spermatogenic failure-20 is characterized by multiple morphologic abnormalities of the flagella, including absent, short, coiled, bent, and irregular-caliber flagella (Tang et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
MVA3 is an autosomal recessive disorder resulting from errors in chromosome segregation. Most affected individuals develop early-onset Wilms tumor and show either aneuploidy or premature chromatid separation in cells. Some patients may have additional developmental features, such as microcephaly, growth retardation, or developmental delay (summary by Yost et al., 2017). For a discussion of genetic heterogeneity of MVA, see MVA1 (257300).
Congenital heart defects and skeletal malformations syndrome (CHDSKM) is characterized by atrial and ventricular septal defects, with aortic root dilation in adulthood. Skeletal defects are variable and include pectus excavatum, scoliosis, and finger contractures, and some patient exhibit joint laxity. Failure to thrive is observed during infancy and early childhood (Wang et al., 2017).
MISSLA is an autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities mainly affecting the upper limb and radial ray. Affected individuals typically have mild intellectual disability, but may have normal development (summary by Reynolds et al., 2017).
Hypomineralized amelogenesis imperfecta type IIIB is characterized by enamel that is reduced in mineral density and is thin, chipped, and absent in places (Smith et al., 2016).
NPHS15 is an autosomal recessive renal disorder characterized by onset of impaired kidney function with proteinuria in the first months of life. The disease course and severity varies widely. Some patients show rapid progression to end-stage renal failure necessitating transplant, whereas others have a more benign course that can be managed with medication. Renal biopsy tends to show glomerular sclerosis and effacement of podocyte foot processes (summary by Bierzynska et al., 2017). For a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
PKD5, a form of autosomal recessive polycystic kidney disease (ARPKD), is characterized by early childhood onset of progressive renal dysfunction associated with enlarged hyperechogenic kidneys that often results in end-stage renal disease in the second or third decade of life. Arterial hypertension is apparent in early childhood (summary by Lu et al., 2017). For a discussion of genetic heterogeneity of polycystic kidney disease, see PKD1 (173900).
MMDS5 is an autosomal recessive disorder characterized mainly by progressive neurologic deterioration beginning in early infancy. Affected individuals have essentially no psychomotor development and have early-onset seizures with neurologic decline and spasticity. Brain imaging shows severe leukodystrophy with evidence of dys- or delayed myelination. Death usually occurs in early childhood (summary by Shukla et al., 2017). For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711).
Skraban-Deardorff syndrome is a neurodevelopmental disorder characterized by delayed psychomotor development with variable intellectual disability, early-onset seizures, and characteristic dysmorphic facial features comprising coarse facies with a prominent maxilla and upper lip revealing the upper gingiva, widely-spaced teeth, and a broad nasal tip (summary by Skraban et al., 2017).
Gingival fibromatosis-5 is an autosomal dominant benign overgrowth disorder characterized by slowly progressive fibrous enlargement of the keratinized gingival tissues. Affected individuals may have diastema, malposition of the teeth, and prolonged retention of primary teeth. Onset is in the first decade. Treatment by surgical resection is generally followed by regrowth of the gingival tissues (summary by Pehlivan et al., 2009).
IMD11B is an autosomal dominant disorder of immune dysfunction characterized by onset of moderate to severe atopic dermatitis in early childhood. Some patients may have recurrent infections and other variable immune abnormalities. Laboratory studies show defects in T-cell activation, increased IgE, and eosinophilia (summary by Ma et al., 2017).
CAKUTHED is an autosomal dominant highly pleiotropic developmental disorder characterized mainly by variable congenital anomalies of the kidney and urinary tract, sometimes resulting in renal dysfunction or failure, dysmorphic facial features, and abnormalities of the outer ear, often with hearing loss. Most patients have global developmental delay (summary by Heidet et al., 2017 and Slavotinek et al., 2017).
PAPA7 is characterized by postaxial polydactyly restricted to the feet, with well-developed nails present on the extra digits and attachment of both the fifth and sixth toes to a broad 2-headed fifth metatarsal (Umair et al., 2017). For a discussion of genetic heterogeneity of postaxial polydactyly, see 174200.
Spermatogenic failure-21 is characterized by acephalic spermatozoa causing male infertility (Li et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
VCRL1 is an autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal defects, and distal mild limb defects. Additional features are variable (summary by Shi et al., 2017). Genetic Heterogeneity of vertebral, cardiac, renal, and limb defects syndrome See also VCRL2 (617661), caused by mutation in the KYNU gene (605197) on chromosome 2q22.
VCRL2 is an autosomal recessive congenital malformation syndrome characterized by vertebral segmentation abnormalities, congenital cardiac defects, renal, and distal mild limb defects. Additional features are variable (summary by Shi et al., 2017). For a discussion of genetic heterogeneity of VCRL, see VCRL1 (617660).
Combined oxidative phosphorylation deficiency-32 is an autosomal recessive neurodegenerative disorder characterized by onset of delayed psychomotor development and developmental regression in infancy. Affected individuals have multiple variable symptoms, including poor or absent speech, inability to walk, and abnormal movements. Brain imaging shows T2-weighted abnormalities in the basal ganglia and brainstem consistent with Leigh syndrome (256000). Patient cells showed decreased activities of mitochondrial respiratory chain complexes, I, III, and IV, as well as impaired mitochondrial translation (summary by Lake et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
EIEE56 is a neurodevelopmental disorder characterized by early-onset seizures in most patients, followed by intellectual disability, variable behavioral abnormalities, and sometimes additional neurologic features, such as ataxia (summary by Guella et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Fraser syndrome is an autosomal recessive malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract (summary by van Haelst et al., 2008). For a general phenotypic description and a discussion of genetic heterogeneity of Fraser syndrome, see 219000.
NELABA is a severe autosomal recessive metabolic disorder characterized by onset at birth of progressive encephalopathy associated with increased serum lactate. Affected individuals have little or no psychomotor development and show brain abnormalities, including cerebral atrophy, cysts, and white matter abnormalities. Some patients die in infancy (summary by Habarou et al., 2017).
CONDBA is a severe progressive neurodegenerative disorder characterized by loss of motor and cognitive skills between ages 2 and 7 years. Affected individuals may have normal development or mild developmental delay, but all eventually lose all motor skills, resulting in inability to walk, absence of language, and profound intellectual disability. Brain imaging shows progressive cerebral and cerebellar atrophy (summary by Edvardson et al., 2017).
Blepharocheilodontic (BCD) syndrome is a disorder that is present at birth. It mainly affects the eyelids (blepharo-), upper lip (-cheilo-), and teeth (-dontic).People with BCD syndrome have lower eyelids that turn out so that the inner surface is exposed (ectropion). The outside of the lower lid may sag away from the eye (euryblepharon), and the eyelids may not be able to close completely (lagophthalmia). There can be extra eyelashes (distichiasis) on the upper eyelids, ranging from a few extra eyelashes to a full extra set. These eyelashes do not grow along the edge of the eyelid with the normal lashes, but out of its inner lining. When the abnormal eyelashes touch the eyeball, they can cause damage to the clear covering of the eye (cornea). Affected individuals may also have widely spaced eyes (hypertelorism), a flat face, and a high forehead.Other features of BCD syndrome usually include openings on both sides of the upper lip (bilateral cleft lip) and an opening in the roof of the mouth (cleft palate). Affected individuals may have fewer teeth than normal (oligodontia) and their teeth are often smaller than usual and cone-shaped. The dental abnormalities affect both primary teeth (sometimes called ""baby teeth"") and secondary (permanent) teeth. Other frequent features include sparse, fine hair and abnormal nails.Occasionally people with BCD syndrome have additional features, including an obstruction of the anal opening (imperforate anus); malformation or absence of the butterfly-shaped gland in the lower neck called the thyroid, resulting in lack of thyroid gland function; or fused fingers or toes (syndactyly). Very rarely, affected individuals have incompletely formed arms or legs (limb reduction defects) or a spinal cord abnormality known as spina bifida.
Pilarowski-Bjornsson syndrome is an autosomal dominant neurodevelopmental disorder characterized by delayed development, intellectual disability, often with autistic features, speech apraxia, and mild dysmorphic features. Some patients may have seizures. The phenotype is somewhat variable (summary by Pilarowski et al., 2017).
Somatic mutations in the GNAS gene have been found predominantly in GH-secreting pituitary adenomas but also in ACTH-secreting adenomas. Mutations in the GNAS gene have been found in about 40% of sporadic somatotrophin adenomas (summary by Mete and Lopes, 2017). For a general description and a discussion of genetic heterogeneity of pituitary adenomas, see PITA1 (102200).
Al Kaissi syndrome is an autosomal recessive developmental disorder characterized by growth retardation, spine malformation, particularly of the cervical spine, dysmorphic facial features, and delayed psychomotor development with moderate to severe intellectual disability (summary by Windpassinger et al., 2017).
PCH11 is an autosomal recessive neurodevelopmental disorder characterized by severely delayed psychomotor development with intellectual disability and poor speech, microcephaly, dysmorphic features, and pontocerebellar hypoplasia on brain imaging. Additional features are more variable (summary by Marin-Valencia et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
MGCA9 is an autosomal recessive disorder characterized by early-onset seizures, severely delayed psychomotor development and intellectual disability. Patients have hypotonia or spasticity, and laboratory investigations show increased serum lactate and 3-methylglutaconic aciduria, suggestive of a mitochondrial defect (summary by Shahrour et al., 2017). For a phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950).
NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding (summary by Wortmann et al., 2017).
IECEE1 is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and resulting in severe to profound intellectual disability with poor or absent speech. Most patients never achieve independent walking. Patients typically have onset of refractory multifocal seizures between the first weeks and years of life, and some may show developmental regression. Additional features, such as hypotonia and cortical visual impairment, are more variable (summary by Myers et al., 2017). Genetic Heterogeneity of Infantile or Early Childhood Epileptic Encephalopathy See also IECEE2 (617829), caused by mutation in the GABRB2 gene (600232) on chromosome 5q34, and IECEE3 (618012), caused by mutation in the ATP6V1A gene (607027) on chromosome 3q13.
Oocyte maturation defect-3 is characterized by infertility, caused by absence of the zona pellucida that results in degeneration of oocytes and 'empty follicle syndrome' on in vitro fertilization procedures (Chen et al., 2017). For a discussion of genetic heterogeneity of oocyte maturation defects, see OOMD1 (615774).
COXPD33 is an autosomal recessive multisystem disorder resulting from a defect in mitochondrial energy metabolism. The phenotype is highly variable, ranging from death in infancy to adult-onset progressive external ophthalmoplegia (PEO) and myopathy. A common finding is cardiomyopathy and increased serum lactate (summary by Feichtinger et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
PLTEID is an autosomal recessive immune-mediated inflammatory disease with highly variable manifestations. More severely affected individuals have recurrent infections, vasculitis, and thrombocytopenia, whereas other patients have mild vasculitis and normal numbers of small platelets without severe infections. Laboratory studies show platelets with abnormal shape, decreased dense granules, and impaired spreading ability, as well as immune dysregulation with increased eosinophils, B cells, IgA and IgE, and autoantibodies (summary by Kahr et al., 2017).
HMN9 is an autosomal dominant neurologic disorder characterized by juvenile onset of slowly progressive distal muscle weakness and atrophy affecting both the lower and upper limbs (summary by Tsai et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN, see HMN type I (HMN1; 182960).
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism, ear abnormalities, and micrognathia. Other features, such as arachnodactyly and visual impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Galloway-Mowat syndrome is a renal-neurologic disease characterized by early-onset nephrotic syndrome associated with microcephaly, gyral abnormalities, and delayed psychomotor development. Most patients have dysmorphic facial features, often including hypertelorism and ear abnormalities. Other features, such as arachnodactyly and visual or hearing impairment, are more variable. Most patients die in the first years of life (summary by Braun et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Oocyte maturation defects due to mutation in PATL2 show phenotypic variability, with some oocytes exhibiting maturation arrest at the germinal vesicle stage and others at the metaphase I stage. In some patients, a few oocytes progress to polar body I; those oocytes either undergo fertilization failure or, in those that are fertilized, early embryonic arrest (Chen et al., 2017).
IMDDHH is a multisystem disorder characterized by immunodeficiency, mildly delayed psychomotor development, poor overall growth from infancy, and hypohomocysteinemia. Additional features, such as congenital heart defects and liver involvement, are more variable (summary by Huppke et al., 2017).
Sweeney-Cox syndrome is characterized by striking facial dysostosis, including hypertelorism, deficiencies of the eyelids and facial bones, cleft palate/velopharyngeal insufficiency, and low-set cupped ears (Kim et al., 2017).
NEDDFL is a neurodevelopmental disorder characterized by delayed psychomotor development and intellectual disability, poor growth with small head size, dysmorphic facial features, and mild abnormalities of the hands and feet (summary by Stankiewicz et al., 2017).
JBTS32 is an autosomal recessive developmental disorder characterized by delayed psychomotor development, intellectual disability, dysmorphic facial features, and postaxial polydactyly. Brain imaging shows cerebellar abnormalities consistent with the molar tooth sign (MTS) (summary by De Mori et al., 2017). For discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (213300).
CNM6 is an autosomal recessive, slowly progressive congenital myopathy with onset in infancy or early childhood. Patients may be hypotonic at birth, but all show delayed motor development and walking difficulties due to muscle weakness mainly affecting the proximal lower and upper limbs. Other features include scapular winging, scoliosis, and mildly decreased respiratory vital capacity. The phenotype and muscle biopsy abnormalities are variable, although centralized nuclei and fiber-type disproportion appear to be a common finding on muscle biopsy. For a discussion of genetic heterogeneity of centronuclear myopathy, see CNM1 (160150).
SHRF is an autosomal recessive disorder characterized by short stature, brachydactyly, dysmorphic facial features, hearing loss, and visual impairment. Onset of the hearing and visual abnormalities, including retinitis pigmentosa, varies from birth to the second decade. Patients have mild intellectual disability and mild cerebellar atrophy with myelination defects on brain imaging (summary by Di Donato et al., 2016).
Joubert syndrome represents a classic ciliopathy characterized by hypotonia, ataxia, cognitive impairment, and a distinctive brain malformation, the 'molar tooth sign.' In addition, retinal dystrophy, cystic kidney disease, liver fibrosis, and polydactyly occur in a subset of patients (summary by Wheway et al., 2015). For a discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (213300).
Kleefstra syndrome-2 is an autosomal dominant neurodevelopmental disorder characterized by delayed psychomotor development, variable intellectual disability, and mild dysmorphic features (summary by Koemans et al., 2017). For a discussion of genetic heterogeneity of Kleefstra syndrome, see KLEFS1 (610253).
MRT61 is an autosomal recessive neurodevelopmental disorder characterized by delayed psychomotor development, moderate to severe intellectual disability, and variable dysmorphic facial features. More severely affected patients may develop refractory seizures and have brain abnormalities, including hypoplasia of the corpus callosum (summary by Alwadei et al., 2016).
Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia is an inborn error of folate metabolism due to deficiency of methylenetetrahydrofolate dehydrogenase-1. Manifestations may include hemolytic uremic syndrome, macrocytosis, epilepsy, hearing loss, retinopathy, mild mental retardation, lymphopenia involving all subsets, and low T-cell receptor excision circles. Folinic acid supplementation is an effective treatment (summary by Ramakrishnan et al., 2016).
The presence of micro-megakaryocytes, hypo-lobed, or non-lobed nuclei in megakaryocytes of all sizes and multiple, widely-separated nuclei. [PMID:27127725]
NEDMIAL is a neurodevelopmental disorder characterized by severely delayed psychomotor development and hypotonia apparent from early infancy, resulting in feeding difficulties, ataxic gait or inability to walk, minimal or absent speech development, and severe intellectual disability, often with behavioral abnormalities, such as hand-flapping. Additional common features may include sleep disorder, nonspecific dysmorphic facial features, and joint hyperlaxity (summary by Lessel et al., 2017).
RHDA3 is an autosomal dominant disorder characterized by abnormal kidney development beginning in utero. The phenotype is highly variable, even within families, and there is evidence for incomplete penetrance. Some affected individuals have bilateral renal agenesis, which is usually fatal in utero or in the perinatal period, whereas others may have unilateral agenesis that is compatible with life, or milder manifestations, such as vesicoureteral reflux (VUR). Female mutation carriers may also have uterine or ovarian abnormalities. Renal aplasia falls at the most severe end of the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT; see 610805) (summary by Brophy et al., 2017 and Sanna-Cherchi et al., 2017). For a discussion of genetic heterogeneity of renal hypodysplasia/aplasia, see RHDA1 (191830).
NDAGSCW is a neurodevelopmental disorder characterized by severely delayed psychomotor development apparent from infancy. Affected individuals have delayed and difficulty walking, intellectual disability, absent speech, and variable additional features, including hip dysplasia, tapering fingers, and seizures. Brain imaging shows decreased cortical white matter, often with decreased cerebellar white matter, thin corpus callosum, and thin brainstem (summary by Lamers et al., 2017).
Coffin-Siris syndrome-6 is characterized by short stature, sparse hair, mild to severe intellectual disability, coarse facial features, and variable behavioral anomalies. Some patients have fifth digit clinodactyly with small nails. Other congenital anomalies and seizures may be present. This description is based on reports of 7 unrelated patients (Shang et al., 2015; Van Paemel et al., 2017; Bramswig et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
GPIBD15 is an autosomal recessive disorder characterized by delayed psychomotor development, variable intellectual disability, hypotonia, early-onset seizures in most patients, and cerebellar atrophy, resulting in cerebellar signs including gait ataxia and dysarthria. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis (summary by Nguyen et al., 2017). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Familial glucocorticoid deficiency-5 is characterized by resistance to adrenocorticotropic hormone (ACTH) and isolated glucocorticoid deficiency, with typical biochemical findings of low serum cortisol levels and high plasma ACTH. Patients commonly present with hyperpigmentation (Prasad et al., 2014). For a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200).
Rescue medication is a generic term used to describe medicines for the treatment of acute episodes of types of chronic disease such as epilepsy.
The number of times a short-acting reliever inhaler is used to treat asthma symptoms to reduce the risk of asthma attack during the period of one week.
The number of prescriptions for a short-acting reliever inhaler to treat asthma symptoms issued during the period of one year.
Mucosal lesion of the alveolar recess of the buccal mucosa caused by ill-fitting prostheses, such as dentures, that caused some form of constant mechanical trauma to the mucosal site.
Damage due to habitual action involving the oral cavity.
Replacement resorption is resorption of the tooth root surface and its substitution by bone resulting in ankylosis.
A temporary situation during which the apex of the tooth root demonstrates the radiographic appearance of resorption following trauma. The finding generally returns to normal following repair within a period of one year.
A type of resorption which is self-limiting and usually occurs following trauma. The disorder manifests as small superficial lacunae in the cementum and may extend in the outermost layer of dentin.
Disorder which may arise as a sequela of traumatic injury, orthodontic tooth movement, or chronic infection of the pulp or periodontal structures.
This disease has characteristics of progressive cerebellar ataxia with pyramidal and spinal cord dysfunction, associated with distinctive MRI anomalies and increased lactate in the abnormal white matter. Onset occurs in early childhood. Epilepsy and cognitive decline have also been described. The syndrome is caused by mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase. Transmission is autosomal recessive.
Malaria without parasitological confirmation.
Indicates whether a healthcare professional has clinical status and rights at healthcare institutions and organisations.
A regular habit of biting on an object such as a pencil or pen.
Linear measurement of the distance or width between molar teeth.
Linear measurement of the distance or width between cuspid teeth.
Modified diet is an alteration to the consistency of foods and liquids for the management of dysphagia.
A spectrum of diseases with manifestation of overgrowth that results from somatic activating mutations in the phosphatidylinositol-3-kinase/AKT/mTOR pathway.
An increased amount of tooth display when smiling compared to rest position.
A rare otorhinolaryngologic disease with characteristics of dysfunction of both peripheral labyrinths or of the eighth nerves, which presents with persistent unsteadiness of gait (particularly in darkness, during eye closure or under impaired visual conditions, or when standing/walking on uneven, soft or wobbly ground) and oscillopsia associated with head movements. The disease may be progressive, presenting no episodes of vertigo, or sequential, presenting recurrent episodes of vertigo.
A rare non-syndromic limb malformation with characteristics of fusion of the proximal or distal tibial and fibular metaphysis and/or diaphysis. The disease is frequently associated with distal positioning of the proximal tibiofibular joint, leg length discrepancy, bowing of the fibula and valgus deformity of the knee.
A rare parkinsonian disorder with characteristics of unilateral body atrophy and slowly progressive, ipsilateral hemiparkinsonian signs (bradykinesia, rigidity, and tremor). Patients typically present with unilateral, action-induced dystonia, in upper or lower limbs, that progresses and becomes bilateral or with tremor which occurs predominantly at rest and progresses to hemiparkinsonism. Scoliosis, scapular winging, raised shoulders, brisk reflexes and extensor plantars are frequently associated.
A rare malignant neoplastic disease characterised by clonal proliferation of myeloid and/or lymphoid precursors harbouring rearrangements in the PDGFRA gene, in the blood, bone marrow and often other tissues as well (spleen, lymph nodes, skin). It usually presents as chronic eosinophilic leukaemia or, less commonly, as acute myeloid leukaemia or T-lymphoblastic leukaemia with eosinophilia. Patients usually present with eosinophilia, anaemia, thrombocytopenia, neutrophilia, splenomegaly, lymphadenopathy, fever, sweating and/or weight loss. Tissue infiltration by eosinophils can manifest with skin rash, erythema, cough, neurological alterations, gastrointestinal symptoms or, rarely, endomyocardial fibrosis and restrictive cardiomyopathy.
A general position for a supernumerary tooth located somewhere other than the midline of the dental arch.
An orally available levorotary enantiomer of ketoconazole with potential steroidogenesis inhibitory activity. Following oral administration, levoketoconazole inhibits three cytochrome P450 family enzymes involved in glucocorticoid biosynthesis, 11beta-hydroxylase (CYP11B1), 17alpha-hydroxylase/17,20-lyase (CYP17A1) and steroid 21-hydroxylase (CYP21A2), which reduces the circulating levels of glucocorticoids. Therefore, this agent may normalize the high concentration of cortisol in the blood seen in patients with Cushing syndrome. Compared to racemic ketoconazole, the levo form is a more potent inhibitor of glucocorticoid synthesis. Additionally, this enantiomer is less likely to inhibit cholesterol 7alpha-hydroxylase (CYP7A1); therefore, its use may reduce the risk of hepatoxicity. Cushing syndrome is caused by high levels of cortisol in the blood either due to excessive production and secretion of corticosteroids, which is often the result of adrenocorticotropic hormone (ACTH)-secreting pituitary or adrenocortical neoplasms, or the use of synthetic corticosteroids.
A synthetic, small molecule targeting the kinesin spindle protein (KSP) with potential antineoplastic activity. KSP inhibitor ARRY-520 specifically inhibits KSP (kinesin-5 or Eg5), resulting in activation of the spindle assembly checkpoint, induction of cell cycle arrest during the mitotic phase, and consequently cell death in tumor cells that are actively dividing. Because KSP is not involved in postmitotic processes, such as neuronal transport, this agent does not cause the peripheral neuropathy that is often associated with tubulin-targeting agents. KSP is an ATP-dependent microtubule motor protein that is essential for the formation of bipolar spindles and the proper segregation of sister chromatids during mitosis.
Scheduled for work days/times that change periodically but does not include night or evening work.
Scheduled for work times that change periodically between days, and/or evenings, and includes some night shifts.
A disorder characterized by an infectious process involving the endometrium. It may extend to the myometrium and parametrial tissues.
A small break in the retina. [HPO:probinson]
An adenoma that arises from the colon. The group of colonic adenomas includes tubular, villous, and tubulovillous adenomas, traditional serrated adenomas, sessile serrated adenomas/polyps, and familial adenomatous polyposis.
Absence (due to failure to form) or underdevelopment of the extremities. [HPO:probinson]
A disorder of large arteries, in particular the aorta, characterized by an accumulation of basophilic ground substance in the media with cyst-like lesions associated with degenerative changes of collagen, elastin and the vascular smooth muscle cells. [HPO:probinson]
Seckel syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (Shanske et al., 1997). Genetic Heterogeneity of Seckel Syndrome Other forms of Seckel syndrome include SCKL2 (606744), caused by mutation in the RBBP8 gene (604124) on chromosome 18q11; SCKL4 (613676), caused by mutation in the CENPJ gene (609279) on chromosome 13q12; SCKL5 (613823), caused by mutation in the CEP152 gene (613529) on chromosome 15q21; SCKL6 (614728), caused by mutation in the CEP63 gene (614724) on chromosome 3q22; SCKL7 (614851), caused by mutation in the NIN gene (608684) on chromosome 14q22; SCKL8 (615807), caused by mutation in the DNA2 gene (601810) on chromosome 10q21; SCKL9 (616777), caused by mutation in the TRAIP gene (605958) on chromosome 3p21; and SCKL10 (617253), caused by mutation in the NSMCE2 gene (617246) on chromosome 8q24. The report of a Seckel syndrome locus on chromosome 14q, designated SCKL3, by Kilinc et al. (2003) was found to be in error; see HISTORY.
Sotos syndrome is characterized by a distinctive facial appearance (broad and prominent forehead, sparse frontotemporal hair, downslanting palpebral fissures, malar flushing, long and narrow face, long chin); learning disability (early developmental delay, mild to severe intellectual impairment); and overgrowth (height and/or head circumference =2 SD above the mean). These three clinical features are considered the cardinal features of Sotos syndrome. Major features of Sotos syndrome include behavioral problems, advanced bone age, cardiac anomalies, cranial MRI/CT abnormalities, joint hyperlaxity / pes planus, maternal preeclampsia, neonatal jaundice, neonatal hypotonia, renal anomalies, scoliosis, and seizures.
Schwartz-Jampel syndrome is a rare condition characterized by permanent muscle stiffness (myotonia) and bone abnormalities known as chondrodysplasia. The signs and symptoms of this condition become apparent sometime after birth, usually in early childhood. Either muscle stiffness or chondrodysplasia can appear first. The muscle and bone abnormalities worsen in childhood, although most affected individuals have a normal lifespan. The specific features of Schwartz-Jampel syndrome vary widely.Myotonia involves continuous tensing (contraction) of muscles used for movement (skeletal muscles) throughout the body. This sustained muscle contraction causes stiffness that interferes with eating, sitting, walking, and other movements. Sustained contraction of muscles in the face leads to a fixed, ""mask-like"" facial expression with narrow eye openings (blepharophimosis) and pursed lips. This facial appearance is very specific to Schwartz-Jampel syndrome. Affected individuals may also be nearsighted and experience abnormal blinking or spasms of the eyelids (blepharospasm).Chondrodysplasia affects the development of the skeleton, particularly the long bones in the arms and legs and the bones of the hips. These bones are shortened and unusually wide at the ends, so affected individuals have short stature. The long bones may also be abnormally curved (bowed). Other bone abnormalities associated with Schwartz-Jampel syndrome include a protruding chest (pectus carinatum), abnormal curvature of the spine, flattened bones of the spine (platyspondyly), and joint abnormalities called contractures that further restrict movement.Researchers originally described two types of Schwartz-Jampel syndrome. Type 1 has the signs and symptoms described above, while type 2 has more severe bone abnormalities and other health problems and is usually life-threatening in early infancy. Researchers have since discovered that the condition they thought was Schwartz-Jampel syndrome type 2 is actually part of another disorder, Stüve-Wiedemann syndrome, which is caused by mutations in a different gene. They have recommended that the designation Schwartz-Jampel syndrome type 2 no longer be used.
Fraser syndrome is an autosomal recessive malformation disorder characterized by cryptophthalmos, syndactyly, and abnormalities of the respiratory and urogenital tract (summary by van Haelst et al., 2008). Genetic Heterogeneity of Fraser Syndrome Fraser syndrome-2 (FRASRS2) is caused by mutation in the FREM2 gene (608945) on chromosome 13q13, and Fraser syndrome-3 (FRASRS3) is caused by mutation in the GRIP1 gene (604597) on chromosome 12q14. See Bowen syndrome (211200) for a comparable but probably distinct syndrome of multiple congenital malformations.
Townes-Brocks syndrome (TBS) is characterized by the triad of imperforate anus (84%), dysplastic ears (87%; overfolded superior helices and preauricular tags; frequently associated with sensorineural and/or conductive hearing impairment [65%]), and thumb malformations (89%; triphalangeal thumbs, duplication of the thumb [preaxial polydactyly], and rarely hypoplasia of the thumbs). Renal impairment (42%), including end-stage renal disease (ESRD), may occur with or without structural abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux). Congenital heart disease occurs in 25%. Foot malformations (52%; flat feet, overlapping toes) and genitourinary malformations (36%) are common. Intellectual disability occurs in approximately 10% of individuals. Rare features include iris coloboma, Duane anomaly, Arnold-Chiari malformation type 1, and growth retardation.
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe). [pmid:16252026]
The erythrokeratodermias are a clinically variable and genetically heterogeneous group of inherited disorders characterized by widespread erythematous plaques, stationary or migratory, associated with nonmigratory hyperkeratoses (summary by Ishida-Yamamoto et al., 1997). The condition is usually present at birth or occurs during the first year but may begin later in childhood or even in early adulthood. Lesions preferentially affect the face, buttocks, and extensor surfaces of the limbs. Palmoplantar keratoderma occurs in about half the cases, but hair, nails, and teeth are not affected (summary by Macfarlane et al., 1991). Genetic Heterogeneity of Erythrokeratodermia Variabilis et Progressiva See EKVP2 (617524), caused by mutation in the GJB4 gene (605425); EKVP3 (617525), caused by mutation in the GJA1 gene (121014); EKVP4 (617526), caused by mutation in the KDSR gene (136440); and EKVP5 (617756), caused by mutation in the KRT83 gene (602765).
Uvula separated into two parts most easily seen at the tip. [pmid:19125428]
A complete duplication of the ureter such that the duplicated ureters with separate insertions into the bladder. [Eurenomics:fschaefer]
A gonad that contains both ovarian follicles and testicular tubular elements. [HPO:probinson]
An extremely rare congenital abnormality characterized by the complete absence of the penis. It may be associated with other genitourinary abnormalities.
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm. [HPO:probinson, pmid:15102623]
A left-right reversal (or mirror reflection"") of the anatomical location of the major thoracic and abdominal organs."" [DDD:dbrown, HPO:probinson]
A form of Ehlers-Danlos syndrome with characteristics of hypotonia, kyphoscoliosis at birth and joint hyperextensibility.
Ehlers-Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of connective tissue disorders defined by joint laxity and skin alterations that include hyperextensibility, atrophic scarring, and bruising. Periodontal EDS (EDSPD; previously designated 'EDS VIII') is a specific subtype of EDS with autosomal dominant inheritance, in which the defining feature is an EDS phenotype combined with severe periodontal inflammation. In childhood, periodontal inflammation in EDSPD is characterized by extensive gingivitis in response to mild plaque accumulation. In the teens, early-onset periodontitis leads to inflammatory destruction of dental attachment and premature loss of teeth. Other clinical features include pretibial hyperpigmentation, acrogeria, skin and gum fragility, scarring, generalized and/or distal joint hypermobility, and bruising out of proportion to trauma. There are also reports of life-threatening complications such as arterial or gastrointestinal ruptures (summary by Kapferer-Seebacher et al., 2016). Genetic Heterogeneity of Ehlers-Danlos Syndrome, Periodontal Type Ehlers-Danlos syndrome periodontal type 2 (EDSPD2; 617174) is caused by mutation in the C1S gene (120580) on chromosome 12p13. Reviews Kapferer-Seebacher et al. (2016) tabulated the clinical features of 93 EDSPD patients with mutations in the C1R or C1S genes (77 and 16 patients, respectively) and observed that the most prevalent features included early-onset periodontitis, gingival recessions, and thin gingiva and/or absence of attached gingiva. Easy bruising was present in most patients, as were pretibial hyperpigmentation, skin fragility, and mildly elastic skin. About half of patients exhibited atrophic scars or wide scarring and/or prominent vasculature. Joint hypermobility was not a consistent finding, and if present was mild and often limited to small joints. Other variable features included recurrent infections, joint pain, flat feet, marfanoid facial features, scoliosis, osteoarthritis, and hernias. A minority of patients had joint dislocations; aneurysms occurred in 4 families, and autoimmune disorders occurred in 1 family. Cancer appeared to be more prevalent in patients with C1S mutations.
Primary localized cutaneous amyloidosis (PLCA) is a condition in which clumps of abnormal proteins called amyloids build up in the skin, specifically in the wave-like projections (dermal papillae) between the top two layers of skin (the dermis and the epidermis). The primary feature of PLCA is patches of skin with abnormal texture or color. The appearance of these patches defines three forms of the condition: lichen amyloidosis, macular amyloidosis, and nodular amyloidosis.Lichen amyloidosis is characterized by severely itchy patches of thickened skin with multiple small bumps. The patches are scaly and reddish brown in color. These patches usually occur on the shins but can also occur on the forearms, other parts of the legs, and elsewhere on the body.In macular amyloidosis, the patches are flat and dark brown. The coloring can have a lacy (reticulated) or rippled appearance, although it is often uniform. Macular amyloidosis patches are most commonly found on the upper back, but they can also occur on other parts of the torso or on the limbs. These patches are mildly itchy.Nodular amyloidosis is characterized by firm, raised bumps (nodules) that are pink, red, or brown. These nodules often occur on the face, torso, limbs, or genitals and are typically not itchy.In some affected individuals, the patches have characteristics of both lichen and macular amyloidosis. These cases are called biphasic amyloidosis.In all forms of PLCA, the abnormal patches of skin usually arise in mid-adulthood. They can remain for months to years and may recur after disappearing, either at the same location or elsewhere. Very rarely, nodular amyloidosis progresses to a life-threatening condition called systemic amyloidosis, in which amyloid deposits accumulate in tissues and organs throughout the body.
Hyperphosphatasia with mental retardation syndrome-1 is an autosomal recessive disorder characterized by mental retardation, various neurologic abnormalities such as seizures and hypotonia, and hyperphosphatasia. Other features include facial dysmorphism and variable degrees of brachytelephalangy (summary by Krawitz et al., 2010). The disorder is caused by a defect in glycosylphosphatidylinositol biosynthesis; see GPIBD1 (610293). Genetic Heterogeneity of Hyperphosphatasia with Mental Retardation Syndrome See also HPMRS2 (614749), caused by mutation in the PIGO gene (614730) on chromosome 9p13; HPMRS3 (614207), caused by mutation in the PGAP2 gene (615187) on chromosome 11p15; HPMRS4 (615716), caused by mutation in the PGAP3 gene (611801) on chromosome 17q12; HPMRS5 (616025), caused by mutation in the PIGW gene (610275) on chromosome 17q12; and HPMRS6 (616809), caused by mutation in the PIGY gene (610662) on chromosome 4q22. Knaus et al. (2018) provided a review of the main clinical features of the different types of HPMRS, noting that some patients have a distinct pattern of facial anomalies that can be detected by computer-assisted comparison, particularly those with mutations in the PIGV and PGAP3 genes. Individuals with HPMRS have variable increased in alkaline phosphatase (AP) as well as variable decreases in GPI-linked proteins that can be detected by flow cytometry. However, there was no clear correlation between AP levels or GPI-linked protein abnormalities and degree of neurologic involvement, mutation class, or gene involved. Knaus et al. (2018) concluded that a distinction between HPMRS and MCAHS (see, e.g., 614080), which is also caused by mutation in genes involved in GPI biosynthesis, may be artificial and even inaccurate, and that all these disorders should be considered and classified under the more encompassing term of 'GPI biosynthesis defects' (GPIBD).
Fanconi renotubular syndrome is a consequence of decreased solute and water reabsorption in the proximal tubule of the kidney. Patients have polydipsia and polyuria with phosphaturia, glycosuria, and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis, and a tendency toward dehydration. Some will eventually develop renal insufficiency. Common laboratory abnormalities include glucosuria with a normal serum glucose, hyperaminoaciduria, hypophosphatemia, progressive renal insufficiency, renal sodium and potassium wasting, acidosis, uricosuria, and low-molecular-weight proteinuria (summary by Lichter-Konecki et al., 2001). Genetic Heterogeneity of Fanconi Renotubular Syndrome Fanconi renotubular syndrome-1 has been mapped to chromosome 15q15.3. See also FRTS2 (613388), caused by mutation in the SLC34A1 gene (182309) on chromosome 5q35; FRTS3 (615605), caused by mutation in the EHHADH gene (607037) on chromosome 3q27; and FRTS4 (616026), which is associated with maturity-onset diabetes of the young (MODY), caused by mutation in the HNF4A gene (600281) on chromosome 20q13.
Diffusely large eye (with megalocornea) associated with glaucoma. []
An autosomal dominant hereditary condition characterized by optic atrophy and progressive visual loss.
Carpenter syndrome is a rare autosomal recessive disorder with the cardinal features of acrocephaly with variable synostosis of the sagittal, lambdoid, and coronal sutures; peculiar facies; brachydactyly of the hands with syndactyly; preaxial polydactyly and syndactyly of the feet; congenital heart defects; growth retardation; mental retardation; hypogenitalism; and obesity. In addition, cerebral malformations, oral and dental abnormalities, coxa valga, genu valgum, hydronephrosis, precocious puberty, and hearing loss may be observed (summary by Altunhan et al., 2011). Genetic Heterogeneity of Carpenter Syndrome Carpenter syndrome-2 (CRPT2; 614976), in which the features of Carpenter syndrome are sometimes associated with defective lateralization, is caused by mutation in the MEGF8 gene (604267).
The essential features of X-linked sideroblastic anemia include the following: (1) a hypochromic microcytic anemia and 2 discrete populations of red blood cells, one microcytic and the other normocytic; (2) marrow ringed sideroblasts, particularly prominent in the late erythroid precursors; (3) a variable hematologic response to pharmacologic doses of pyridoxine; and (4) systemic iron overload secondary to chronic ineffective erythropoiesis. The age of clinical onset of the disorder can vary from in utero to the ninth decade. Whereas males are preferentially affected, females may present with clinically severe anemia. More commonly, female carriers of the disease have an increased red blood cell distribution width and sometimes erythrocyte dimorphism (Fleming, 2002). Genetic Heterogeneity of Sideroblastic Anemia See also SIDBA2 (205950), caused by mutation in the SLC25A38 gene (610819) on chromosome 3p22; SIDBA3 (616860), caused by mutation in the GLRX5 gene (609588) on chromosome 14q32; and SIDBA4 (182170), caused by mutation in the HSPA9 gene (600548) on chromosome 5q31.
Dehydrated hereditary stomatocytosis (DHS), also known as hereditary xerocytosis, is an autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. DHS erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. DHS patients typically exhibit mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration (summary by Zarychanski et al., 2012). Patients may also show perinatal edema and pseudohyperkalemia due to loss of K+ from red cells stored at room temperature. A minor proportion of red cells appear as stomatocytes on blood films. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. The course of DHS is frequently associated with iron overload, which may lead to hepatosiderosis (summary by Albuisson et al., 2013). Dehydrated red blood cells, including those from hereditary xerocytosis patients, show delayed infection rates to Plasmodium in vitro, suggesting a potential protective mechanism against malaria (Tiffert et al., 2005). A polymorphism in PIEZO1 that is enriched in populations of African descent and results in xerocytosis conferred resistance to Plasmodium infection in vitro (see 611184.0016). The 'leaky red blood cells' in familial pseudohyperkalemia show a temperature-dependent loss of potassium when stored at room temperature, manifesting as apparent hyperkalemia. The red blood cells show a reduced life span in vivo, but there is no frank hemolysis. Studies of cation content and transport show a marginal increase in permeability at 37 degrees C and a degree of cellular dehydration, qualitatively similar to the changes seen in dehydrated hereditary stomatocytosis. Physiologic studies show that the passive leak of potassium has an abnormal temperature dependence, such that the leak is less sensitive to temperature than that in normal cells (summary by Iolascon et al., 1999). Carella et al. (2004) noted that 3 clinical forms of pseudohyperkalemia unassociated with hematologic manifestations, based predominantly on the leak-temperature dependence curve, had been reported: (1) pseudohyperkalemia Edinburgh, in which the curve has a shallow slope; (2) pseudohyperkalemia Chiswick or Falkirk (see 609153), in which the curve is shouldered; and (3) pseudohyperkalemia Cardiff (see 609153), in which the temperature dependence of the leak shows a 'U-shaped' profile with a minimum at 23 degrees C. Gore et al. (2004) stated that potassium-flux temperature profiles are consistent both from year to year in an individual as well as consistent within affected members of a pedigree. Genetic Heterogeneity of Hereditary Stomatocytosis Dehydrated hereditary stomatocytosis-2 (DHS2; 616689) is caused by mutation in the KCNN4 gene (602754) on chromosome 19q13. Another form of stomatocytosis, involving familial pseudohyperkalemia with minimal hematologic abnormalities (PSHK2; 609153), is caused by mutation in the ABCB6 gene (605452) on chromosome 2q35. Cryohydrocytosis (CHC; 185020) is caused by mutation in the SLC4A1 gene (109270) on chromosome 17q21, and stomatin-deficient cryohydrocytosis with neurologic defects (SDCHCN; 608885) is caused by mutation in the SLC2A1 gene (138140) on chromosome 1p34. An overhydrated form of hereditary stomatocytosis (OHST; 185000) is caused by mutation in the RHAG gene (180297) on chromosome 6p12. See 137280 for a discussion of the association of familial stomatocytosis and hypertrophic gastritis in the dog, an autosomal recessive syndrome. Reviews Delaunay (2004) reviewed genetic disorders of red cell membrane permeability to monovalent cations, noting 'inevitable' overlap between entities based on clinical phenotype. Bruce (2009) provided a review of hereditary stomatocytosis and cation-leaky red cells, stating that consistent features include hemolytic anemia, a monovalent cation leak, and changes in red cell morphology that appear to follow a continuum, from normal discocyte to stomatocyte to echinocyte in DHS, and from discocyte to stomatocyte to spherocyte to fragmentation in OHST. Bruce (2009) suggested that the underlying pathologic mechanism might involve misfolded mutant proteins that escape the quality control system of the cell and reach the red cell membrane, where they disrupt the red cell membrane structure and cause a cation leak that alters the hydration of the red cell, thereby changing the morphology and viability of the cell. King and Zanella (2013) provided an overview of 2 groups of nonimmune hereditary red cell membrane disorders caused by defects in membrane proteins located in distinct layers of the red cell membrane: red cell cytoskeleton disorders, including hereditary spherocytosis (see 182900), hereditary elliptocytosis (see 611804), and hereditary pyropoikilocytosis (266140); and cation permeability disorders of the red cell membrane, or hereditary stomatocytoses, including DHS, OHST, CHC, and PSHK. The authors noted that because there is no specific screening test for the hereditary stomatocytoses, a preliminary diagnosis is based on the presence of a compensated hemolytic anemia, macrocytosis, and a temperature- or time-dependent pseudohyperkalemia in some patients. King et al. (2015) reported the International Council for Standardization in Haematology (ICSH) guidelines for laboratory diagnosis of nonimmune hereditary red cell membrane disorders.
A disorder characterized by laboratory test results that indicate an increased number of white blood cells in the blood.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the hip. [UToronto:chum]
Malfunction of the abducens nerve as manifested by impairment of the ability of the affected eye to be moved outward. [HPO:probinson]
A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger). [HPO:probinson, pmid:16344298]
Tremor that occurs during any voluntary movement. It may include visually or non-visually guided movements. Tremor during target directed movement is called intention tremor. []
Focal segmental glomerulosclerosis (FSGS) is a pathologic finding in several renal disorders that manifest clinically as proteinuria and progressive decline in renal function. Some patients with FSGS develop the clinical entity called 'nephrotic syndrome' (see NPHS1; 256300), which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. However, patients with FSGS may have proteinuria in the nephrotic range without other features of the nephrotic syndrome (summary by D'Agati et al., 2004; Mathis et al., 1998). D'Agati et al. (2011) provided a detailed review of FSGS, emphasizing that the disorder results from defects of the podocyte. Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (see NOMENCLATURE section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. Genetic Heterogeneity of Focal Segmental Glomerulosclerosis and Nephrotic Syndrome Focal segmental glomerulosclerosis and nephrotic syndrome are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also FSGS2 (603965), caused by mutation in the TRPC6 gene (603652); FSGS3 (607832), associated with variation in the CD2AP gene (604241); FSGS4 (612551), mapped to chromosome 22q12; FSGS5 (613237), caused by mutation in the INF2 gene (610982); FSGS6 (614131), caused by mutation in the MYO1E gene (601479); FSGS7 (616002), caused by mutation in the PAX2 gene (167409); FSGS8 (616032), caused by mutation in the ANLN gene (616027); and FSGS9 (616220), caused by mutation in the CRB2 gene (609720). See also NPHS1 (256300), caused by mutation in the NPHS1 gene (602716); NPHS2 (600995), caused by mutation in the podocin gene (604766); NPHS3 (610725), caused by mutation in the PLCE1 gene (608414); and NPHS4 (256370), caused by mutation in the WT1 gene (607102).
Stage IB includes: IB (T1b, N0, M0); IB1(T1b1, N0, M0); IB2 (T1b2, N0, M0). T1b: Clinically visible lesion confined to the cervix or microscopic lesion greater than T1a/IA2. T1b1: Clinically visible lesion 4.0 cm or less in greatest dimension. T1b2: Clinically visible lesion more than 4.0 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IA includes: IA (T1a, N0, M0); IA1 (T1a1, N0, M0); IA2 (T1a2, N0, M0). T1a: Invasive carcinoma diagnosed only by microscopy. Stromal invasion with a maximum depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less. Vascular space involvement, venous or lymphatic, does not affect classification. T1a1: Measured stromal invasion 3.0 mm or less in depth and 7.0 or less horizontal spread. T1a2: Measured stromal invasion more than 3.0 mm and not more than 5.0 mm with a horizontal spread 7.0 mm or less. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IVA includes: T4, Any N, M0). T4: Tumor invades mucosa of bladder or rectum, and/or extends beyond true pelvis (bullous edema is not sufficient to classify a tumor as T4). M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage I includes: (T1, N0, M0). T1: Tumor confined to vagina. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage II includes: T2, N0, M0. T2: Tumor invades paravaginal tissues but not to pelvic wall. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage III includes: (T1-3, N1, M0) and (T3, N0, M0). T1: Tumor confined to vagina. T2: Tumor invades paravaginal tissues but not to pelvic wall. T3: Tumor extends to pelvic wall. N0: No regional lymph node metastasis. N1: Pelvic or inguinal lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage IVA includes: T4, Any N, M0. T4: Tumor invades mucosa of the bladder or rectum and/or extends beyond the true pelvis (bullous edema is not sufficient evidence to classify a tumor as T4). M0: No distant metastasis. (AJCC 6th and 7th eds.)
Hairy cell leukemia that is resistant to treatment.
A glioblastoma that occurs during childhood.
An anaplastic astrocytoma that arises from the central nervous system and occurs during childhood.
Hot water epilepsy (HWE) is a form of reflex or sensory epilepsy in which seizures are precipitated by immersion in hot water or pouring of hot water over the head during bathing. The seizures are usually complex partial, but about 33% of patients experience secondary generalization. There are no additional neurologic abnormalities (Satishchandra, 2003).
VLDLR-associated cerebellar hypoplasia (VLDLR-CH) is characterized by non-progressive congenital ataxia that is predominantly truncal and results in delayed ambulation, moderate-to-profound intellectual disability, dysarthria, strabismus, and seizures. Children either learn to walk very late (often after age 6 years) or never achieve independent ambulation.
A disorder characterized by an infectious process involving the bronchi.
Congenital onset of a marked decrease in the number of granulocytes. [HPO:probinson]
Immunodeficiency, centromeric instability, and facial dysmorphism (ICF) syndrome is a rare autosomal recessive disease characterized by facial dysmorphism, immunoglobulin deficiency, and branching of chromosomes 1, 9, and 16 after phytohemagglutinin (PHA) stimulation of lymphocytes. Hypomethylation of DNA of a small fraction of the genome is an unusual feature of ICF patients that is explained by mutations in the DNMT3B gene in some, but not all, ICF patients (Hagleitner et al., 2008). Genetic Heterogeneity of Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome See also ICF2 (614069), caused by mutation in the ZBTB24 gene (614064) on chromosome 6q21; ICF3 (616910), caused by mutation in the CDCA7 gene (609937) on chromosome 2q31; and ICF4 (616911), caused by mutation in the HELLS gene (603946) on chromosome 10q23.
Obesity in which excess fat is accumulated primarily in the area of the abdomen.
Many types of nonsyndromic congenital nail disorders (NDNC) have been described. Twenty-nail dystrophy (TND), also known as trachyonychia (from the Greek for 'rough nails'), is an autosomal dominant nail dystrophy characterized by excessive longitudinal striations and numerous superficial pits on the nails, which have a distinctive rough sandpaper-like appearance. Occasionally some nails are spared. The slowly progressive condition is usually apparent at birth and may be self-limiting, with spontaneous resolution in some patients (summary by Sehgal, 2007). TND is referred to here as nonsyndromic congenital nail disorder-1 (NCNC1). Genetic Heterogeneity of Nonsyndromic Congenital Nail Disorders Other nonsyndromic congenital nail disorders include koilonychia (NDNC2; 149300); leukonychia (NDNC3; 151600) caused by mutation in the PLCD1 gene (602142) on chromosome 3p22; anonychia/hyponychia (NDNC4; 206800) caused by mutation in the RSPO4 gene (610673) on chromosome 20p13; partial onycholysis with scleronychia (NDNC5; 164800); anonychia of thumbs with onychodystrophy of other nails (NDNC6; 107000); onychodystrophy mapping to chromosome 17p13 (NDNC7; 605779); toenail dystrophy (NDNC8; 607523) caused by mutation in the COL7A1 gene (120120) on chromosome 3p21; onychodystrophy mapping to chromosome 17q25.1-q25.3 (NDNC9; 614149); and onychodystrophy (NDNC10; 614157) caused by mutation in the FZD6 gene (603409) on chromosome 8q22.
Avascular necrosis of the femoral head (ANFH) is a debilitating disease that usually leads to destruction of the hip joint in the third to fifth decade of life. The disorder is characterized by progressive pain in the groin, mechanical failure of the subchondral bone, and degeneration of the hip joint. Nearly one-half of patients require hip replacement before 40 years of age. ANFH represents a specific form of the broader disease category of osteonecrosis (summary by Mont and Hungerford, 1995). Genetic Heterogeneity of Primary Avascular Necrosis of the Femoral Head ANFH2 is caused by mutation in the TRPV4 gene (605427) on chromosome 12q24. Mutation in COL2A1 has also been found in Legg-Calves-Perthes disease (LCPD; 150600), a form of ANFH in growing children.
Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium. [pmid:19125436, pmid:9683597]
Decreased width of the bony bridge of the nose. [pmid:19152422]
A row of beadlike prominences at the junction of a rib and its cartilage, resembling a rosary. [HPO:probinson]
Any structural abnormality or abnormal count of granulocytes. [HPO:probinson]
Syndactyly with fusion of toes two and three. [HPO:sdoelken]
An autosomal recessive disorder associated with mutation(s) in at least one of four genes (WDR35, IFT122, WDR19, or IFT43). It is characterized by distinctive abnormalities of the face and skull, in association with developmental abnormalities of the structures derived from ectodermal tissues.
Uncombable hair syndrome is characterized by silvery, blond, or straw-colored scalp hair that is dry, frizzy, and wiry, has a characteristic sheen, stands away from the scalp in multiple directions, and is impossible to comb. This hair shaft disorder occurs in children and improves with age. The hair growth rate can range from slow to normal (summary by U. Basmanav et al., 2016). Genetic Heterogeneity of Uncombable Hair Syndrome See UHS2 (617251), caused by mutation in the TGM3 gene (600238) on chromosome 20p12, and UHS3 (617252), caused by mutation in the TCHH gene (190370) on chromosome 1q21.
Atrophy of the cortex of the cerebrum. [HPO:probinson]
Partial or complete wasting (loss) of brain tissue that was once present. [HPO:probinson]
Eosinophilic esophagitis (EOE) has an incidence of approximately 1 per 10,000 people. Symptoms include difficulty feeding, failure to thrive, vomiting, epigastric or chest pain, dysphagia, and food impaction. Individuals with EOE are predominantly young males with a high rate of atopic disease, and the diagnosis is made by endoscopy and biopsy findings of isolated eosinophils in the esophagus (summary by Rothenberg et al., 2010). Genetic Heterogeneity of Eosinophilic Esophagitis Eosinophilic esophagitis-1 (EOE1) is associated with variation at chromosome 7q11.2. Another locus (EOE2; 613412) has been been associated with variation in the TSLP gene (607003) on chromosome 5q22.
An elevated concentration of high-density lipoprotein cholesterol (HDL) in the blood. [HPO:probinson]
Congenital symmetric circumferential skin creases is characterized by the folding of excess skin, which leads to ringed creases, primarily of the limbs. Affected individuals also exhibit intellectual disability, cleft palate, and dysmorphic features (summary by Isrie et al., 2015). Genetic Heterogeneity of Congenital Symmetric Circumferential Skin Creases CSCSC2 (616734) is caused by mutation in the MAPRE2 gene (605789) on chromosome 18q12.
Primary biliary cirrhosis (PBC) is a chronic, progressive cholestatic liver disease that usually affects middle-aged women and eventually leads to liver failure (summary by Kaplan, 1996). Genetic Heterogeneity of Primary Biliary Cirrhosis Primary biliary cirrhosis-1 (PBC1) is significantly associated with SNPs at the IL12A locus (161560) on chromosome 3p12-q13.2. Significant association of PBC has also been shown with SNPs at the HLA-DQB1 locus (604305) on chromosome 6p21.3 (PBC2; 613007), at the IL12RB2 locus (601642) on chromosome 1p31.2 (PBC3; 613008), at the IRF5 (607218)-TNPO3 (610032) locus on chromosome 7q32 (PBC4; 614220), and at the ZPBP2 locus (608499) on chromosome 17q12-q21 (PBC5; 614221). See also Reynolds syndrome (613471), in which primary biliary cirrhosis is a feature.
Any structural anomaly of the kidney. [HPO:probinson]
A disorder characterized by an infectious process involving the pelvic cavity.
A disorder characterized by substernal discomfort due to insufficient myocardial oxygenation e.g., angina pectoris.
Arthrochalasia-type EDS is distinguished from other types of EDS by the frequency of congenital hip dislocation and extreme joint laxity with recurrent joint subluxations and minimal skin involvement (Byers et al., 1997; Giunta et al., 2008). Genetic Heterogeneity of Arthrochalasia-type Ehlers-Danlos Syndrome See EDSARTH2 (617821), caused by mutation in the COL1A2 gene (120160).
Unroofed coronary sinus (CS) is a rare congenital cardiac anomaly in which there is partial (either focal or fenestrated) or complete absence of the roof of the CS, which results in a communication between the CS and the LA. Unroofed CS is the rarest type of atrial septal defect. It is often associated with persistent left superior vena cava (LSVC) and other forms of complex congenital heart disease, usually heterotaxia syndromes. The morphological types have been classified into 4 groups: Type I, completely unroofed with persistent LSVC; type II, completely unroofed without persistent LSVC; type III, partially unroofed mid portion; and type IV, partially unroofed terminal portion. [PMID:19398672]
An abnormally reduced number of granulocytes in the blood. [HPO:probinson]
A recurrent form of pancreatitis. [HPO:probinson]
A disorder characterized by a sudden or brief burst of light.
Normal color vision in humans is trichromatic, being based on 3 classes of cone that are maximally sensitive to light at approximately 420 nm (blue cones; 613522), 530 nm (green cones; 300821), and 560 nm (red cones; 300822). Comparison by neural circuits of light absorption by the 3 classes of cone photoreceptors allows perception of red, yellow, green, and blue colors individually or in various combinations. Dichromatic color vision is severely defective color vision based on the use of only 2 types of photoreceptors, blue plus green (protanopia; see 303900) or blue plus red (deuteranopia). Anomalous trichromacy is trichromatic color vision based on a blue, green, and an anomalous red-like photoreceptor (protanomaly), or a blue, red, and an anomalous green-like photoreceptor (deuteranomaly). The color vision defect is generally mild but may in certain cases be severe. Common variation in red-green color vision exists among both normal and color-deficient individuals (review by Deeb, 2005).
Insidious, chronic and recurrent disorder, characterised by small and elevated oval corneal intraepithelial, whitish-gray opacities, extending to the entire anterior surface of the cornea of both eyes. Corneal lesions show a tendency for the central pupillary area distribution with mild or absent conjunctival inflammation and no association to systemic disease.
Stage 0is includes: Tis, N0, M0. Tis: Carcinoma in situ: ""flat tumor"". N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Oxycephaly (from Greek oxus, sharp, and kephalos, head) refers to a conical or pointed shape of the skull. [HPO:curators]
The presence of developmental dysplasia of the hip. [HPO:probinson]
A pathological narrowing of the esophagus that is caused by the development of a ring of scar tissue that constricts the esophageal lumen. [HPO:probinson]
A finding based on laboratory test results that indicate an increase in the level of alkaline phosphatase in a blood specimen.
A type of sacrococcygeal teratoma located anterior to the sacrum and entirely inside the body (Altman type IV). [HPO:probinson]
Patient complaints (symptoms), physical/laboratory findings(signs) related to the cardiovascular system.
A subtype of fundus hemorrhage occuring within the neurosensory retina. Intraretinal haemorrhages may be 'dot' or' blot' shaped or flame shaped depending upon their depth within the retina. [UManchester:psergouniotis]
A type of sideroblastic anemia that is not responsive to treatment. [HPO:probinson]
A manifest or latent ocular deviation in which one or other eye tends to deviate temporally. [ORCID:0000-0003-0986-4123]
Abnormal thickening of the skin of the palms of the hands and the soles of the feet. [HPO:probinson]
An abnormal high-pitched noisy sound, occurring during inhalation or exhalation caused by the incomplete obstruction in the throat. [HPO:probinson]
Myelocystocele is characterized by a large, ependyma-lined, cystic dilation of the caudal end of the central canal of the spinal cord; it projects dorsally through a lamina defect, with overlying varying amounts of lipomatous subcutaneous tissue. Myelocystoceles are associated with a tethered cord and meningocele, which communicates with the spinal subarachnoid space, but not with the central canal cyst. [PMID:9514174, UToronto:chum]
Primary hypertrophic osteoarthropathy is a familial disorder characterized by digital clubbing and osteoarthropathy, with variable features of pachydermia, delayed closure of the fontanels, and congenital heart disease. Secondary hypertrophic osteoarthropathy, or pulmonary hypertrophic osteoarthropathy, is a different disorder characterized by digital clubbing secondary to acquired diseases, most commonly intrathoracic neoplasm (Uppal et al., 2008). Touraine et al. (1935) recognized pachydermoperiostosis as a familial disorder with 3 clinical presentations or forms: a complete form characterized by periostosis and pachydermia; an incomplete form with bone changes but without pachydermia; and a 'forme fruste' with pachydermia and minimal skeletal changes. Genetic Heterogeneity PHOAR2 (614441) is caused by mutation in the SLCO2A1 gene (601460) on chromosome 3q22.1-q22.2. Families with an autosomal dominant form of primary hypertrophic osteoarthropathy have also been reported (PHOAD; 167100).
Aggressive periodontitis, which may be generalized or localized, is characterized by severe and protracted gingival infections, leading to tooth loss. Amounts of microbial deposits are generally inconsistent with the severity of periodontal tissue destruction and the progression of attachment and bone loss may be self arresting (American Academy of Periodontology, 2000). The term 'aggressive periodontitis' replaced the terms 'early-onset,' 'prepubertal,' or 'juvenile periodontitis' at a 1999 International workshop for a classification of periodontal disease and conditions, where it was decided that the classification terminology should not be age dependent or require knowledge of rates of progression (Armitage, 1999). Genetic Heterogeneity of Aggressive Periodontitis Aggressive periodontitis-2 (608526) has been mapped to chromosome 1q25.
A benign or malignant neuroendocrine neoplasm of the sympathetic nervous system that secretes catecholamines. It arises from the chromaffin cells of the adrenal medulla. Clinical presentation includes headaches, palpitations, chest and abdominal pain, hypertension, fever, and tremor. Microscopically, a characteristic nesting (zellballen) growth pattern is usually seen. Other growth patterns including trabecular pattern may also be present.
The presence of a paralyzed diaphragm. [HPO:probinson, pmid:3612666]
A malignant neoplasm arising exclusively from the soft tissues.
A type of sarcoma (A connective tissue neoplasm formed by proliferation of mesodermal cells) that develops from soft tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. [HPO:probinson]
A group of breathing disorders characterized by abnormal respiratory patterns or insufficient ventilation during sleep.
A swelling formed at the base of umbilicus associated with a patent urachus which results from an allantoic remnant. The urachus is a fibrous remnant of the allantois which communicates from the apex of the urinary bladder to the umbilicus. Failed obliteration of the urachus can lead to various abnormalities: urachal cyst, urachal diverticulum, sinus or patent urachus - the most common type. Allantoic cysts in infants with patent urachus can be formed due to the drainage of urine into the umbilical cord, or in uncommon situations, after leakage of hypo-osmotic urine into the Wharton's jelly. [PMID:24950576, PMID:26213613, UToronto:chum]
A cutaneous eruption that consists of multiple (at least two) concentric erythematous rings. []
A disorder characterized by an eruption of papules and pustules, typically appearing in face, scalp, upper chest and back.
A type of chromosomal aberration reduced resistance of chromosomes to change or deterioration. [HPO:probinson]
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones. [HPO:probinson, pmid:20212494]
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss. [ORCID:0000-0003-0986-4123]
A congenital neural tube closure defect resulting in the protrusion of the brain through a skull opening. When the protrusion includes the meninges, the term encephalomeningocele is used.
A manifest or latent ocular deviation in which one or other eye tends to deviate nasally. [ORCID:0000-0003-0986-4123]
A disorder characterized by an uncomfortable and temporary sensation of intense body warmth, flushing, sometimes accompanied by sweating upon cooling.
A disorder characterized by acute inflammation to the vermiform appendix caused by a pathogenic agent with gangrenous changes resulting in the rupture of the appendiceal wall. The appendiceal wall rupture causes the release of inflammatory and bacterial contents from the appendiceal lumen into the abdominal cavity.
Waldenstrom macroglobulinemia that does not respond to treatment.
Stage I includes: I (T1, N0, M0); IA (T1a, N0, M0); IA1 (T1a1, N0, M0); IA2 (T1a2, N0, M0); IB (T1b, N0, M0); IB1(T1b1, N0, M0); IB2 (T1b2, N0, M0). T1: Cervical carcinoma confined to uterus (extension to corpus should be disregarded). T1a: Invasive carcinoma diagnosed only by microscopy. Stromal invasion with a maximum depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less. Vascular space involvement, venous or lymphatic, does not affect classification. T1a1: Measured stromal invasion 3.0 mm or less in depth and 7.0 or less horizontal spread. T1a2: Measured stromal invasion more than 3.0mm and not more than 5.0 mm with a horizontal spread 7.0mm or less. T1b: Clinically visible lesion confined to the cervix or microscopic lesion greater than T1a/IA2. T1b1: Clinically visible lesion 4.0 cm or less in greatest dimension. T1b2: Clinically visible lesion more than 4.0 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Stage II includes: II (T2, N0, M0); IIA (T2a, N0, M0); IIB (T2b, N0, M0). T2: Cervical carcinoma invades beyond uterus but not to pelvic wall or to lower third of vagina. T2a: Tumor without parametrial invasion. T2b: Tumor with parametrial invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th ed.)
Stage III includes: III (T3, N0, M0); IIIA (T3a, N0, M0); IIIB (T1, N1, M0), (T2, N1, M0), (T3a, N1, M0), (T3b, Any N, M0). T3: Tumor extends to pelvic wall and/or involves lower third of vagina, and/or causes hydronephrosis or non-functioning kidney. T3a: Tumor involves lower third of vagina, no extension to pelvic wall. T3b: Tumor extends to pelvic wall and/or causes hydronephrosis or non functioning kidney. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
Increased susceptibility to middle ear infections, as manifested by recurrent episodes of middle ear infections [ORCID:0000-0001-7941-2961]
Blue and green cones only; no functional red cones. [DDD:gblack]
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by mid-adult onset of recurrent ischemic stroke, cognitive decline progressing to dementia, a history of migraine with aura, mood disturbance, apathy, and diffuse white matter lesions and subcortical infarcts on neuroimaging.
Benign familial infantile seizures (BFIS) is a seizure disorder of early childhood with age at onset from 3 months up to 24 months. It is characterized by brief seizures beginning with slow deviation of the head and eyes to 1 side and progressing to generalized motor arrest and hypotonia, apnea and cyanosis, and limb jerks. Seizures usually occur in clusters over a day or several days. The ictal EEG shows focal parietal-temporal activity, whereas the interictal EEG is normal. Concurrent and subsequent psychomotor and neurologic development are normal (Franzoni et al., 2005). See also benign familial neonatal seizures (BFNS1; 121200). Deprez et al. (2009) provided a review of the genetics of epilepsy syndromes starting in the first year of life, and included a diagnostic algorithm. Genetic Heterogeneity of Benign Familial Infantile Seizures The BFIS1 locus has been mapped to chromosome 19q. BFIS2 (605751) is caused by mutation in the PRRT2 gene on chromosome 16p11. BFIS3 (607745), which is caused by the mutations in the SCN2A gene (182390) on chromosome 2q24, has a slightly earlier age at onset and is sometimes termed benign familial 'neonatal-infantile' seizures. BFIS4 (612627) has been mapped to chromosome 1p. BFIS5 (617080) is caused by mutation in the SCN8A gene (600702) on chromosome 12q13. BFIS6 (see 610353) is caused by mutation in the CHRNA2 gene (118502) on chromosome 8p21.
Zimmermann-Laband syndrome is a rare disorder characterized by gingival fibromatosis, dysplastic or absent nails, hypoplasia of the distal phalanges, scoliosis, hepatosplenomegaly, hirsutism, and abnormalities of the cartilage of the nose and/or ears (summary by Balasubramanian and Parker, 2010). Genetic Heterogeneity of Zimmermann-Laband Syndrome Zimmermann-Laband syndrome-2 (ZLS2; 616455) is caused by mutation in the ATP6V1B2 gene (606939) on chromosome 8p21.
Feingold syndrome 1 (referred to as FS1 in this GeneReview) is characterized by digital anomalies (shortening of the 2nd and 5th middle phalanx of the hand, clinodactyly of the 5th finger, syndactyly of toes 2-3 and/or 4-5, thumb hypoplasia), microcephaly, facial dysmorphism (short palpebral fissures and micrognathia), gastrointestinal atresias (primarily esophageal and/or duodenal), and mild-to-moderate learning disability.
Knobloch syndrome is an autosomal recessive developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia (summary by Aldahmesh et al., 2011).
The 3C syndrome, also known as Ritscher-Schinzel syndrome, is a developmental malformation syndrome characterized by craniofacial abnormalities, congenital heart defects, and cerebellar brain malformations. Facial features include prominent occiput, prominent forehead, low-set ears, downslanting palpebral fissures, depressed nasal bridge, and micrognathia. Cardiac defects can include septal defects and aortic stenosis, among others, and brain imaging shows Dandy-Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation. Affected individuals have severe developmental delay (summary by Leonardi et al., 2001; Seidahmed et al., 2011). Genetic Heterogeneity of Ritscher-Schinzel Syndrome See also RTSC2 (300963), caused by mutation in the CCDC22 gene (300859) on chromosome Xp11.
A progressive condition marked by bilateral nerve deafness and neurological disorders involving several cranial and, less commonly, spinal nerves.
Abnormal elevation of the floor of the posterior fossa including occipital condyles and foramen magnum. [HPO:probinson, pmid:10084535]
Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness in which all other visual functions, including visual acuity, visual field, and color vision, are usually normal. A typical feature of the disease is a golden or gray-white discoloration of the fundus that disappears in the dark-adapted state and reappears shortly after the onset of light (Mizuo phenomenon, or Mizuo-Nakamura phenomenon). The course of dark adaptation of rod photoreceptors is extremely retarded, whereas that of cones appears to proceed normally (summary by Fuchs et al., 1995). Genetic Heterogeneity of Oguchi Disease Oguchi disease-2 (CSNBO2) is caused by mutation in the rhodopsin kinase gene (GRK1; 180381) on chromosome 13q34.
Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: 1 with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). Genetic Heterogeneity and Classification of Methylglutaconic Aciduria Methylglutaconic aciduria is a clinically and genetically heterogeneous disorder. Type II MGCA (MGCA2), also known as Barth syndrome (BTHS; 302060), is caused by mutation in the tafazzin gene (TAZ; 300394) on chromosome Xq28. It is characterized by mitochondrial cardiomyopathy, short stature, skeletal myopathy, and recurrent infections; cognitive development is normal. Type III MGCA (MGCA3; 258501), caused by mutation in the OPA3 gene (606580) on chromosome 19q13, involves optic atrophy, movement disorder, and spastic paraplegia. In types II and III, the elevations of 3-methylglutaconate and 3-methylglutarate in urine are modest. Type IV MGCA (MGCA4; 250951) represents an unclassified group of patients who have severe psychomotor retardation and cerebellar dysgenesis. Type V MGCA (MGCA5; 610198), caused by mutation in the DNAJC19 gene (608977) on chromosome 3q26, is characterized by early-onset dilated cardiomyopathy with conduction defects, nonprogressive cerebellar ataxia, testicular dysgenesis, and growth failure in addition to 3-methylglutaconic aciduria (Chitayat et al., 1992; Davey et al., 2006). Type VI MGCA (MGCA6; 614739), caused by mutation in the SERAC1 gene (614725) on chromosome 6q25, includes deafness, encephalopathy, and a Leigh-like syndrome. Type VII MGCA (MGCA7; 616271), caused by mutation in the CLPB gene (616254) on chromosome 11q13, includes cataracts, neurologic involvement, and neutropenia. Type VIII MCGA (MGCA8; 617248) is caused by mutation in the HTRA2 gene (606441) on chromosome 2p13. Type IX MCGA (MGCA9; 617698) is caused by mutation in the TIMM50 gene (607381) on chromosome 19q13. Eriguchi et al. (2006) noted that type I MGCA is very rare, with only 13 patients reported in the literature as of 2003. Wortmann et al. (2013) proposed a pathomechanism-based classification for 'inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature.'
A disorder characterized by inhibition of fetal growth resulting in the inability of the fetus to achieve its potential weight.
Urticaria caused by physical agents, such as heat, cold, light, friction. [PMID:11702618]
Presence of persistent islands of renal blastema in the postnatal kidney, anywhere within a renal lobe (a portion of a kidney consisting of a renal pyramid and the renal cortex above it). [DDD:rscott]
Abnormally persistent foci of embryonal immature blastema located in the superficial cortical region (perilobar). [DDD:rscott]
Focal seizure with eyelid myoclonia, not eyelid myoclonias in the context of absence seizures. [HPO:ihelbig]
An elevation in bone density in one or more diaphyses. Sclerosis is normally detected on a radiograph as an area of increased opacity. [HPO:probinson]
Hypoplastic left heart syndrome results from defective development of the aorta proximal to the entrance of the ductus arteriosus and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged (Brekke, 1953). Genetic Heterogeneity of Hypoplastic Left Heart Syndrome Hypoplastic left heart syndrome-2 (HLHS2; 614435) is caused by mutation in the NKX2-5 gene (600584) on chromosome 5q35.1. Somatic mutations in the HAND1 gene (602406) have been identified in tissue samples from patients with HLHS.
A disorder characterized by an infectious process involving the breast.
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). Genetic Heterogeneity of Asphyxiating Thoracic Dysplasia SRTD1 has been mapped to chromosome 15q13. See also SRTD2 (611263), caused by mutation in the IFT80 gene (611177); SRTD3 (613091), caused by mutation in the DYNC2H1 gene (603297); SRTD4 (613819), caused by mutation in the TTC21B gene (612014); SRTD5 (614376), caused by mutation in the WDR19 gene (608151); SRTD6 (263520), caused by mutation in the NEK1 gene (604588); SRTD7 (614091), caused by mutation in the WDR35 gene (613602); SRTD8 (615503), caused by mutation in the WDR60 gene (615462); SRTD9 (266920), caused by mutation in the IFT140 gene (614620); SRTD10 (615630), caused by mutation in the IFT172 gene (607386); SRTD11 (615633), caused by mutation in the WDR34 gene (613363); SRTD13 (616300), caused by mutation in the CEP120 gene (613446); SRTD14 (616546), caused by mutation in the KIAA0586 gene (610178); SRTD15 (617088), caused by mutation in the DYNC2LI1 gene (617083); SRTD16 (617102), caused by mutation in the IFT52 gene (617094); SRTD17 (617405), caused by mutation in the TCTEX1D2 gene (617353); SRTD18 (617866), caused by mutation in the IFT43 gene (614068); SRTD19 (617895), caused by mutation in the IFT81 gene (605489); and SRTD20 (617925), caused by mutation in the INTU gene (610621). See also SRTD12 (Beemer-Langer syndrome; 269860).
Progressive supranuclear palsy (PSP) is the second most frequent cause of degenerative parkinsonism. In addition to parkinsonism, the clinical symptoms include early postural instability, supranuclear gaze palsy, and cognitive decline. Neuropathologically, the disorder is characterized by abundant neurofibrillary tangles, which differ in both distribution and composition from those associated with Alzheimer disease. In progressive supranuclear palsy, the tangles are primarily localized to subcortical regions and are found in both neurons and glia, whereas in Alzheimer disease they are more widespread, largely cortical, and limited to neurons. They also have different characteristics at the ultrastructural level (Baker et al., 1999). Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of frontotemporal dementia (FTD; 600274), primary progressive aphasia (PPA), corticobasal degeneration (CBD), progressive supranuclear palsy, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease,' and that the term 'Pick disease' (172700) should be restricted to the pathologic finding of Pick bodies. Genetic Heterogeneity of Progressive Supranuclear Palsy Other loci for PSP have been mapped to chromosome 1q31 (PSNP2; 609454) and 11p12-p11 (PSNP3; 610898). See also Parkinson-dementia syndrome and atypical progressive supranuclear palsy (260540).
Stage IA includes: pT1, N0, M0, S0. pT1: Tumor limited to the testis and epididymis without vascular/lymphatic invasion; tumor may invade into the tunica albuginea but not the tunica vaginalis. N0: No regional lymph node metastasis. M0: No distant metastasis. S0: Marker study levels within normal limits. (AJCC 6th and 7th eds.)
Stage IB includes: (pT2, N0, M0, S0); (pT3, N0, M0, S0); (pT4, N0, M0, S0). pT2: Tumor limited to the testis and epididymis with vascular/lymphatic invasion, or tumor extending through the tunica albuginea with involvement of the tunica vaginalis. pT3: Tumor invades the spermatic cord with or without vascular/lymphatic invasion. pT4: Tumor invades the scrotum with or without vascular/lymphatic invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. S0: Marker study levels within normal limits. (AJCC 6th and 7th eds.)
Stage IIB includes: T2b, N0, M0. T2b: Tumor with parametrial invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 6th and 7th eds.)
An abnormality of amino acid metabolism characterized by a decreased rate of propionyl-CoA carboxylase activity. [HPO:probinson]
A disorder characterized by a change in the sound and/or speed of the voice.
Stage IVB includes: Any T, Any N, MI. M1: Distant metastasis. (AJCC 6th and 7th eds.)
Central areolar choroidal dystrophy (CACD) is a hereditary retinal disorder that principally affects the macula, often resulting in a well-defined area of atrophy of the retinal pigment epithelium (RPE) and choriocapillaris in the center of the macula. Dysfunction of macular photoreceptors usually leads to a decrease in visual acuity, generally occurring between the ages of 30 and 60 years (summary by Boon et al., 2009). Genetic Heterogeneity of Central Areolar Choroidal Dystrophy CACD2 (613105) is caused by mutation in the PRPH2 gene (179605) on chromosome 6p21. See also CACD3 (613144) for a family in which linkage to the PRPH2 gene and chromosome 17p13 has been excluded.
A pregnancy induced hypertensive state that occurs after 20 weeks of gestation characterized by an increase in blood pressure, along with body swelling and proteinuria.
Familial cold autoinflammatory syndrome is characterized clinically by recurrent attacks of a maculopapular rash associated with arthralgias, myalgias, fever and chills, and swelling of the extremities after exposure to cold. Despite the first description of 'cold urticaria' (Kile and Rusk, 1940) the rash in most patients is nonpruritic and nonurticarial. Rarely, some patients may also develop late-onset renal amyloidosis (Hoffman et al., 2000). Overlapping syndromes also caused by mutation in the NLRP3 gene include Muckle-Wells syndrome (CAPS2; 191900), which has a high frequency of amyloidosis and late-onset sensorineural deafness, and chronic neurologic cutaneous and articular syndrome (CINCA, CAPS3; 607115), which shows earlier onset and a more severe phenotype. Genetic Heterogeneity of Familial Cold Autoinflammatory Syndrome See also FCAS2 (611762), caused by mutation in the NLRP12 gene (609648) on chromosome 19q13; FCAS3 (614468), caused by mutation in the PLCG2 gene (600220) on chromosome 16q23; and FCAS4 (616115), caused by mutation in the NLRC4 gene (606831) on chromosome 2p22.
A dental anomaly characterized by the presence of a two fused teeth. [HPO:ibailleulforestier]
Clinical otosclerosis, the single most common cause of hearing impairment, is characterized by isolated endochondral bone sclerosis of the labyrinthine capsule. Otosclerotic foci invade the stapediovestibular joint (oval window) and interfere with free motion of the stapes. Mean age of onset is in the third decade and 90% of affected persons are under 50 years of age at the time of diagnosis. Approximately 10% of affected persons develop profound sensorineural hearing loss across all frequencies (summary by Tomek et al., 1998). Genetic Heterogeneity of Otosclerosis The locus associated with otosclerosis-1 (OTSC1) has been mapped to chromosome 15q26.1. Other loci associated with otosclerosis include OTSC2 (605727) on chromosome 7q; OTSC3 (608244) on chromosome 6p; OTSC4 (611571) on chromosome 16q; OTSC5 (608787) on chromosome 3q22-q24; OTSC7 (611572) on chromosome 6q13; OTSC8 (612096) on chromosome 9p13.1-q21.11; and OTSC10 (615589) on chromosome 1q41-q44. The symbols OTSC6 and OTSC9 were reserved by the HUGO Gene Nomenclature Committee on January 30, 2003 and February 10, 2009, respectively, for as yet unpublished loci for otosclerosis.
Craniosynostosis is a primary abnormality of skull growth involving premature fusion of the cranial sutures such that the growth velocity of the skull often cannot match that of the developing brain. This produces skull deformity and, in some cases, raises intracranial pressure, which must be treated promptly to avoid permanent neurodevelopmental disability (summary by Fitzpatrick, 2013). Mutation in the TWIST1 has been found to cause coronal and sagittal forms of craniosynostosis. Genetic Heterogeneity of Craniosynostosis Craniosynostosis-2 (CRS2; 604757) is caused by mutation in the MSX2 gene (123101) on chromosome 5q35. Craniosynostosis-3 (CRS3; 615314) is caused by mutation in the TCF12 gene (600480) on chromosome 15q21. Craniosynostosis-4 (CRS4; 600775) is caused by mutation in the ERF gene (611888) on chromosome 19q13. Susceptibility to craniosynostosis-5 (CRS5; 615529) is conferred by variation in the ALX4 gene (605420) on chromosome 11p11. Craniosynostosis-6 (CRS6; 616602) is caused by mutation in the ZIC1 gene (600470) on chromosome 3q24. Susceptibility to craniosynostosis-7 (CRS7; 617439) is conferred by variation in the SMAD6 gene (602931) on chromosome 15q22.
Total anomalous pulmonary venous return (TAPVR) is a cyanotic form of congenital heart defect in which the pulmonary veins fail to enter the left atrium and instead drain into the right atrium or one of the venous tributaries (summary by Bleyl et al., 1994).
A developmental defect characterized by abnormal connection of or more pulmonary veins to the superior or inferior vena cava, the right atrium, or the coronary sinus, resulting in a left-to-right shunt of oxygenated blood. [HPO:probinson]
An inflammatory neuropathy belonging to the clinical spectrum of Guillain-Barré syndrome. The clinical course is divided into three phases. The first phase (lasting a few weeks) has characteristics of rapidly progressive muscle weakness. It is symmetrical and may cause acute neuromuscular paralysis. Sensory disturbances, intense pains, and cramps may also occur. During the second phase (variable duration), symptoms become stable but other manifestations (cardiac arrhythmias, hyper/hypotension and gastric dysmotility) may occur. During the third (recovery) phase, lasting a few months or longer, symptoms slowly regress. Many patients have residual findings (weakness, sensory disturbances, fatigue or pain) for many months or even years. In the majority of cases, an infectious disease precedes the onset of limb weakness, with Campylobacter jejuni infection being the most frequent initiating event.
A disorder characterized by walking difficulties.
A disorder characterized by excessive levels of thyroid hormone in the body. Common causes include an overactive thyroid gland or thyroid hormone overdose.
A finding of cutaneous inflammatory reaction occurring as a result of exposure to biologically effective levels of ionizing radiation.
A finding of leakage of urine due to breakdown of a kidney anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by a reduction in the strength of the muscles of the pelvic floor.
A finding of protrusion of the intestinal stoma (surgically created opening on the surface of the body) above the abdominal surface.
A disorder characterized by an infectious process involving the bones.
A disorder characterized by an intense adverse reaction (usually immunologic) developing at the site of an injection.
A disorder characterized by swelling due to excessive fluid accumulation in the upper or lower extremities.
A disorder characterized by a circumscribed, erosive lesion on the skin.
A disorder characterized by reduced sweating.
A disorder characterized by an inflammation involving the larynx.
A disorder characterized by intense painful sensation along a nerve or group of nerves.
A finding based on pulmonary function test results that indicate an abnormal vital capacity (amount of exhaled after a maximum inhalation) when compared to the predicted value.
A disorder characterized by an infectious process involving the spleen.
A disorder characterized by an infectious process involving the middle ear.
A finding of displacement of the urostomy.
A finding of narrowing of the gastrointestinal stoma (surgically created opening on the surface of the body).
A disorder characterized by a rupture in the jejunal wall.
A disorder characterized by a narrowing of the lumen of the anal canal.
A disorder characterized by the loss of lymph fluid into the surrounding tissue or body cavity.
A disorder characterized by a sensation of marked discomfort in a joint.
A disorder characterized by an inability to rest, relax or be still.
A finding of leakage due to breakdown of a gastrointestinal anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by an individual seeing spots before their eyes. The spots are shadows of opaque cell fragments in the vitreous humor or lens.
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the duodenal wall.
A low-fucose, human-mouse chimeric IgG1 monoclonal antibody directed against the ganglioside GD3, a surface antigen expressed on many malignant melanoma cells, with potential antineoplastic activity. Monoclonal antibody KW-2871 binds to GD3-positive cells, thereby initiating antibody-dependent cytotoxicity against GD3-positive cells. This agent is prepared by fusing murine immunoglobulin (Ig) light and heavy variable regions derived from the murine IgG3 antibody KM-641 to a human constant (Fc) region. The low fucose content of the oligosaccharide side chains of this antibody may enhance binding of the antibody Fc region to lymphocyte Fc receptors. Check for ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=467926&idtype=1"" active clinical trials or ""http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=467926&idtype=1&closed=1"" closed clinical trials using this agent. (""http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C61095"" NCI Thesaurus)
Van Maldergem syndrome is an autosomal recessive disorder characterized by intellectual disability, typical craniofacial features, auditory malformations resulting in hearing loss, and skeletal and limb malformations. Some patients have renal hypoplasia. Brain MRI typically shows periventricular nodular heterotopia (summary by Cappello et al., 2013). Genetic Heterogeneity of Van Maldergem Syndrome See also VMLDS2 (615546), caused by mutation in the FAT4 gene (612411) on chromosome 4q28.
Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. Cardiac failure and cardiomyopathy have been observed in later stages. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, paraphasic errors, and relative preservation of memory, and later stages by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 55 years.
Autosomal dominant centronuclear myopathy is a congenital myopathy characterized by slowly progressive muscular weakness and wasting. The disorder involves mainly limb girdle, trunk, and neck muscles but may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life, and some affected individuals become wheelchair-bound in their fifties. Ptosis and limitation of eye movements occur frequently. The most prominent histopathologic features include high frequency of centrally located nuclei in a large number of extrafusal muscle fibers (which is the basis of the name of the disorder), radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers (summary by Bitoun et al., 2005). Genetic Heterogeneity of Centronuclear Myopathy Centronuclear myopathy is a genetically heterogeneous disorder. See also X-linked CNM (CNMX; 310400), caused by mutation in the MTM1 gene (300415) on chromosome Xq28; CNM2 (255200), caused by mutation in the BIN1 gene (601248) on chromosome 2q14; CNM4 (614807), caused by mutation in the CCDC78 gene (614666) on chromosome 16p13; CNM5 (615959), caused by mutation in the SPEG gene (615950) on chromosome 2q35; and CNM6 (617760), caused by mutation in the ZAK gene (609479) on chromosome 2q31. The mutation in the MYF6 gene that was reported to cause a form of CNM, formerly designated CNM3, has been reclassified as a variant of unknown significance; see 159991.0001. Some patients with mutation in the RYR1 gene (180901) have findings of centronuclear myopathy on skeletal muscle biopsy (see 255320).
Macular dystrophies are inherited retinal dystrophies in which various forms of deposits, pigmentary changes, and atrophic lesions are observed in the macula lutea, the cone-rich region of the central retina. Vitelliform macular dystrophies (VMDs) form a subset of macular dystrophies characterized by round yellow deposits, usually at the center of the macula and containing lipofuscin, a chemically heterogeneous pigment visualized by autofluorescence imaging of the fundus (summary by Manes et al., 2013). In contrast to typical VMD (see 153700), patients with atypical VMD may exhibit normal electrooculography, even when severe loss of vision is present, and fluorescein angiography is thus the most reliable test for identifying affected individuals (Hittner et al., 1984). Genetic Heterogeneity of Vitelliform Macular Dystrophy See also vitelliform macular dystrophy-2 (VMD2; 153700), caused by mutation in the BEST1 gene (607854) on chromosome 11q; VMD3 (608161), caused by mutation in the PRPH2 gene (179605) on chromosome 6p21; VMD4 (616151), caused by mutation in the IMPG1 gene (602870) on chromosome 6q14; and VMD5 (616152), caused by mutation in the IMPG2 gene (607056) on chromosome 3q12.
Decreased ratio between the upper and the lower segment of the body, where the lower segment is defined as the length between the top of pubic symphysis to floor, and the upper segment is defined as the top of head to top of pubic symphysis. [HPO:probinson]
Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare autosomal recessive oxidative phosphorylation disorder specific to skeletal muscle and bone marrow (Bykhovskaya et al., 2004). Genetic Heterogeneity of Myopathy, Lactic Acidosis, and Sideroblastic Anemia MLASA2 (613561) is caused by mutation in the YARS2 gene (610957) on chromosome 12p11. MLASA3 (500011) is caused by heteroplasmic mutation in the mitochondrially-encoded MTATP6 gene (516060).
A rare, autosomal dominant hereditary syndrome characterized by hypercalcemia, abnormally high levels of parathyroid hormone, and isolated hyperfunctioning parathyroid tumors.
Hidradenitis suppurativa, also known as acne inversa, is a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin. The nodules become inflamed and painful. They tend to break open (rupture), causing abscesses that drain fluid and pus. As the abscesses heal, they produce significant scarring of the skin.The signs and symptoms of hidradenitis suppurativa appear after puberty, usually in a person's teens or twenties. Nodules are most likely to form in the armpits and groin. They may also develop around the anus, on the buttocks, or under the breasts. In some cases, nodules appear in other areas, such as the nape of the neck, waist, and inner thighs.The recurrent nodules and abscesses cause chronic pain and can lead to self-consciousness, social isolation, and depression. Rarely, nodules on the buttocks can develop into a type of skin cancer called squamous cell carcinoma.
Bulimia nervosa (BN) is a psychiatric disorder characterized by episodes of binge-eating (eating an unusually large amount of food in a discrete period of time and feeling out of control), compensatory behavior (e.g., self-induced vomiting or laxative abuse), and over-concern with weight and shape. Eating disorders such as bulimia nervosa are complex disorders that can be influenced by many genes.
HGPPS is an autosomal recessive neurologic disorder characterized by eye movement abnormalities apparent from birth and childhood-onset progressive scoliosis. These features are associated with a developmental malformation of the brainstem including hypoplasia of the pons and cerebellar peduncles and defective decussation of certain neuronal systems. Cognitive function is normal (summary by Bosley et al., 2005). Genetic Heterogeneity of Familial Horizontal Gaze Palsy With Progressive Scoliosis See also HGPPS2 (617542), caused by mutation in the DCC gene (120470) on chromosome 18q21.
B-cell expansion with NFKB and T-cell anergy is an autosomal dominant disorder characterized by onset in infancy of splenomegaly and polyclonal expansion of B cells, resulting in peripheral lymphocytosis. Affected individuals also show mild immune dysfunction, including some defective antibody responses and T-cell anergy. There may be a predisposition to the development of B-cell malignancy (summary by Snow et al., 2012).
DCX-related disorders include the neuronal migration disorders: Classic thick lissencephaly (more severe anteriorly), usually in males. Subcortical band heterotopia (SBH), primarily in females. Males with classic DCX-related lissencephaly typically have early and profound cognitive and language impairment, cerebral palsy, and epileptic seizures. The clinical phenotype in females with SBH varies widely with cognitive abilities that range from average or mild cognitive impairment to severe intellectual disability and language impairment. Seizures, which frequently are refractory to antiepileptic medication, may be either focal or generalized and behavioral problems may also be observed. In DCX-related lissencephaly and SBH the severity of the clinical manifestation correlates roughly with the degree of the underlying brain malformation as observed in cerebral imaging.
Sclerosis (increased density) affecting vertebral end plates. [HPO:curators]
A rare, autosomal recessive inherited skeletal muscle disorder caused by mutation in the dysferlin gene. It affects young adults and is characterized by weakness and atrophy in the muscles of the upper and lower limbs.
Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is characterized by thrombocytopenia that progresses to pancytopenia, in association with congenital proximal fusion of the radius and ulna that results in extremely limited pronation and supination of the forearm (summary by Niihori et al., 2015). Genetic Heterogeneity of Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia Radioulnar synostosis with amegakaryocytic thrombocytopenia-2 (RUSAT2; 616738) is caused by heterozygous mutation in the MECOM gene (165215) on chromosome 3q26.
Hereditary hypotrichosis simplex (HHS) is a rare form of nonsyndromic hereditary hypotrichosis without characteristic hair shaft anomalies. Affected individuals typically show normal hair at birth, but hair loss and thinning of the hair shaft start during early childhood and progress with age. HHS can be largely divided into 2 forms: the scalp-limited form (e.g., 146520) and the generalized form, in which all body hair is affected. HHS is characterized by progressive hair follicle miniaturization, which is a typical feature of androgenetic alopecia (see 109200). HHS can be inherited either as an autosomal dominant or autosomal recessive trait (e.g., HYPT8, 278150) (summary by Shimomura et al., 2010). Genetic Heterogeneity of Nonsyndromic Hypotrichosis See also HYPT2 (146520), caused by mutation in the CDSN gene (602593) on chromosome 6p21; HYPT3 (613981), caused by mutation in the KRT74 gene (608248) on chromosome 12q13; HYPT4 (146550), caused by mutation in upstream regulatory regions of the HR gene (602302) on chromosome 8p21; HYPT5 (612841), mapped to chromosome 1p21-q21; HYPT6 (607903), caused by mutation in the DSG4 gene (607892) on chromosome 18q12; HYPT7 (604379), caused by mutation in the LIPH gene (607365) on chromosome 3q27; HYPT8 (278150), caused by mutation in the LPAR6 gene (609239) on chromosome 13q14; HYPT9 (614237), mapped to chromosome 10q11.23-q22.3; HYPT10 (614238), mapped to chromosome 7p22.3-p21.3; HYPT11 (615059), caused by mutation in the SNRPE gene (128260) on chromosome 1q32; HYPT12 (615885), caused by mutation in the RPL21 gene (603636) on chromosome 13q12; HYPT13 (615896), caused by mutation in the KRT71 gene (608245) on chromosome 12q13; and HYPT14 (618275), caused by mutation in the LSS gene (600909) on chromosome 21q22.
Underdevelopment of both forearm bones, the ulna and the radius, resulting in a shortened forearm. [HPO:probinson]
Heimler syndrome-1 (HMLR1), which represents the mildest end of the peroxisomal biogenesis disorder spectrum (see PBD1A, 214100), is a rare autosomal recessive disorder characterized by sensorineural hearing loss, enamel hyoplasia of the secondary dentition, and nail abnormalities (Ratbi et al., 2015). Genetic Heterogeneity of Heimler Syndrome Another form of Heimler syndrome (HMLR2; 616617) is caused by mutation in the PEX6 gene (601498) on chromosome 6p21.
Combined deficiency of factor V (612309) and factor VIII (300841) is characterized by bleeding symptoms similar to those in hemophilia (306700) or parahemophilia (227400), caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma FV and FVIII antigen and activity levels are in the range of 5 to 30%. Inheritance of F5F8D is autosomal recessive and distinct from the coinheritance of FV deficiency and FVIII deficiency (summary by Zhang and Ginsburg, 2004). Genetic Heterogeneity of Combined Deficiency of Factor V and Factor VIII Another form of combined deficiency of factor V and factor VII (F5F8D2; 613625) is caused by mutation in the MCFD2 gene (607788) on chromosome 2.
DEPDC5-related epilepsy encompasses a range of epilepsy syndromes, almost all of which are characterized by focal seizures, with seizure onset in a discrete area of the brain. While most individuals with DEPDC5-related epilepsy have a normal brain MRI, some have epilepsy associated with a cortical malformation, usually focal cortical dysplasia. Seizure syndromes include familial focal epilepsy with variable foci (FFEVF), autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), familial mesial temporal lobe epilepsies (FMTLE), autosomal dominant epilepsy with auditory features (ADEAF), and infantile spasms. Although psychomotor development is usually normal, intellectual disability or autism spectrum disorder has been reported in some individuals.
A multisystem disorder with characteristics of neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with low serum gamma-glutamyl transferase activity. The phenotype is variable, even within the same family and cases may go undiagnosed as not all the patients present with the three cardinal features. Mutations in the VPS33B gene (15q26.1) have been found in 75% of ARC families, as well as mutations in the VIPAR gene (C14ORF133), encoding a protein that complexes with VPS33B. Most patients die within the first year of life despite supportive care for metabolic acidosis and cholestasis and those surviving longer show cirrhosis and severe developmental delay.
The blepharocheilodontic syndrome is a rare autosomal dominant disorder characterized by lower eyelid ectropion, upper eyelid distichiasis, euryblepharon, bilateral cleft lip and palate, and conical teeth. An additional rare manifestation is imperforate anus (summary by Weaver et al., 2010).
A rare condition with features of congenital ectrodactylous limb malformations associated with tibial aplasia or hypoplasia. The expression of the phenotype is highly variable and ranges from bilateral aplasia of tibiae and split-hand/split-foot deformity (tetramonodactyly or transverse hemimelia) to the mildest visible manifestation, hypoplastic big toes. Additional malformations may include distal hypoplasia or bifurcation of femora, hypo or aplasia of ulnae, and minor anomalies such as aplasia of patellae, postaxial and intermediate polydactyly in association with split-hand deformity, and cup-shaped ears. The syndrome is generally inherited in an autosomal dominant manner with reduced penetrance.
Hypobetalipoproteinemia (FBHL) and abetalipoproteinemia (ABL; 200100) are rare diseases characterized by hypocholesterolemia and malabsorption of lipid-soluble vitamins leading to retinal degeneration, neuropathy, and coagulopathy. Hepatic steatosis is also common. The root cause of both disorders is improper packaging and secretion of apolipoprotein B-containing particles. Obligate heterozygous parents of FBHL patients typically have half normal levels of apoB-containing lipoproteins consistent with autosomal codominant inheritance, whereas obligate heterozygous parents of ABL patients usually have normal lipids consistent with autosomal recessive inheritance (summary by Lee and Hegele, 2014). Genetic Heterogeneity of Familial Hypobetalipoproteinemia Familial hypobetalipoproteinemia-2 (FHBL2; 605019) is caused by mutation in the ANGPTL3 gene (604774) on chromosome 1p31.
Anterior segment dysgeneses (ASGD or ASMD) are a heterogeneous group of developmental disorders affecting the anterior segment of the eye, including the cornea, iris, lens, trabecular meshwork, and Schlemm canal. The clinical features of ASGD include iris hypoplasia, an enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, an abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface (summary by Cheong et al., 2016). Anterior segment dysgenesis is sometimes divided into subtypes including aniridia (see 106210), Axenfeld and Rieger anomalies, iridogoniodysgenesis, Peters anomaly, and posterior embryotoxon (Gould and John, 2002). Some patients with ASGD1 have been reported with the Peters anomaly subtype. In its simplist form, Peters anomaly involves a central corneal opacity, but it may also involve adherent iris strands. Some patients have keratolenticular content or cataract. The underlying defects in this form of congenital corneal opacity reside in the posterior stroma, Descemet membrane, and corneal endothelium. The disorder results from abnormal migration or function of neural crest cells and may include abnormalities of other anterior segment structures, such as the lens and iris (summary by Withers et al., 1999).
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) disease is characterized by progressive gastrointestinal dysmotility (manifesting as early satiety, nausea, dysphagia, gastroesophageal reflux, postprandial emesis, episodic abdominal pain and/or distention, and diarrhea); cachexia; ptosis/ophthalmoplegia or ophthalmoparesis; leukoencephalopathy; and demyelinating peripheral neuropathy (manifesting as paresthesias (tingling, numbness, and pain) and symmetric and distal weakness more prominently affecting the lower extremities). The order in which manifestations appear is unpredictable. Onset is usually between the first and fifth decades; in about 60% of individuals, symptoms begin before age 20 years.
Auriculocondylar syndrome (ARCND) is an autosomal dominant disorder of the first and second pharyngeal arches and is characterized by malformed ears (question mark ears), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia (summary by Masotti et al., 2008). Genetic Heterogeneity of Auriculocondylar Syndrome Auriculocondylar syndrome-2 (ARCND2; 614669) is caused by mutation in the PLCB4 gene (600810) on chromosome 20p12.3-p12.2. ARCND3 (615706) is caused by mutation in the EDN1 gene (131240) on chromosome 6p24. See also 612798 for isolated question mark ears.
Horizontal nystagmus dating from or present at birth. [HPO:curators]
Patterned dystrophies of the retinal pigment epithelium (RPE) refer to a heterogeneous group of macular disorders, characterized by an abnormal accumulation of lipofuscin in the RPE. The lipofuscin is most apparent in the macular area, and its distribution can show various sizes and shapes. High inter- and intrafamilial variability has been described, and retinitis pigmentosa (RP; see 268000)-like changes have sometimes been observed in association with patterned dystrophies (summary by Vaclavik et al., 2012). Three main varieties of patterned dystrophy of the RPE have been described: reticular ('fishnet-like') dystrophy (see 179840 and 267800), macroreticular ('spider-shaped') dystrophy, and butterfly-shaped pigment dystrophy of the fovea. Genetic Heterogeneity of Patterned Macular Dystrophy Also see MDPT2 (608970), caused by mutation in the CTNNA1 gene (116805) on chromosome 5q31; and MDPT3 (617111), caused by mutation in the MAPKAPK3 gene (602130) on chromosome 3p21.
The Meier-Gorlin syndrome is a rare disorder characterized by severe intrauterine and postnatal growth retardation, microcephaly, bilateral microtia, and aplasia or hypoplasia of the patellae (summary by Shalev and Hall, 2003). While almost all cases have primordial dwarfism with substantial prenatal and postnatal growth retardation, not all cases have microcephaly, and microtia and absent/hypoplastic patella are absent in some. Despite the presence of microcephaly, intellect is usually normal (Bicknell et al., 2011). Genetic Heterogeneity of Meier-Gorlin Syndrome Most forms of Meier-Gorlin syndrome are autosomal recessive disorders, including Meier-Gorlin syndrome-1; Meier-Gorlin syndrome-2 (613800), caused by mutation in the ORC4 gene (603056) on chromosome 2q23; Meier-Gorlin syndrome-3 (613803), caused by mutation in the ORC6 gene (607213) on chromosome 16q11; Meier-Gorlin syndrome-4 (613804), caused by mutation in the CDT1 gene (605525) on chromosome 16q24; Meier-Gorlin syndrome-5 (613805), caused by mutation in the CDC6 gene (602627) on chromosome 17q21; Meier-Gorlin syndrome-7 (617063), caused by mutation in the CDC45L gene (603465) on chromosome 22q11; and Meier-Gorlin syndrome-8 (617564), caused by mutation in the MCM5 gene (602696) on chromosome 22q12. An autosomal dominant form of the disorder, Meier-Gorlin syndrome-6 (616835), is caused by mutation in the GMNN gene (602842) on chromosome 6p22.
Ehlers-Danlos syndrome spondylodysplastic type 1 is characterized by short stature, developmental anomalies of the forearm bones and elbow, and bowing of extremities, in addition to the classic stigmata of Ehlers-Danlos syndrome, including joint laxity, skin hyperextensibility, and poor wound healing. Significant developmental delay is not a consistent feature (Guo et al., 2013). Genetic Heterogeneity of Ehlers-Danlos Syndrome, Spondylodysplastic Type See EDSSPD2 (615349), caused by mutation in the B3GALT6 gene (615291), and EDSSPD3 (612350), caused by mutation in the SLC39A13 gene (608735).
Laing distal myopathy is characterized by early-onset weakness (usually before age 5 years) that initially involves the dorsiflexors of the ankles and great toes and then the finger extensors, especially those of the third and fourth fingers. Weakness of the neck flexors is seen in most affected individuals and mild facial weakness is often present. After distal weakness has been present for more than ten years, mild proximal weakness may be observed. Life expectancy is normal.
An electrocardiographic finding of a regular supraventricular tachycardia which utilizes an atrioventricular bypass tract as its retrograde limb (orthodromic tachycardia) or as its antegrade limb (antidromic tachycardia). QRS complexes during sinus rhythm may show preexcitation. During orthodromic tachycardia the preexcitation is not present and a retrograde P wave may appear after the QRS complex. During antidromic tachycardia the QRS complex is preexcited. (CDISC)
A reduced ability to secrete gonadotropins, which are protein hormones secreted by gonadotrope cells of the anterior pituitary gland, including the hormones follitropin (FSH) and luteinizing hormone (LH). [DDD:spark]
Stage IIA includes: IIA (T2a, N0, M0); IIA1 (T2a1, N0, M0); IIA2 (T2a2, N0, M0). T2a: Tumor without parametrial invasion. T2a1: Clinically visible lesion 4.0 cm or less in greatest dimension. T2a2: Clinically visible lesion more than 4.0 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 7th ed.)
Stage IIA includes: (Any pT/TX, N1, M0, S0); (Any pT/TX, N1, M0, S1). pTX: Primary tumor cannot be assessed. N1: Metastasis with a lymph node mass 2 cm or less in greatest dimension; or multiple lymph nodes, none more than 2cm in greatest dimension. M0: No distant metastasis. S0: Marker study levels within normal limits. S1: LDH less than 1.5 x N (N indicates the upper limit of normal for the LDH assay) and hCG less than 5,000 and AFP less than 1,000. (AJCC 6th and 7th eds.)
Stage IIB includes: (Any pT/TX, N2, M0, S0); (Any pT/TX, N2, M0, S1). pTX: Primary tumor cannot be assessed. N2: Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, any one mass greater than 2 cm but not more than 5 cm in greatest dimension. M0: No distant metastasis. S0: Marker study levels within normal limits. S1: LDH less than 1.5 x N (N indicates the upper limit of normal for the LDH assay) and hCG less than 5,000 and AFP less than 1,000. (AJCC 6th and 7th eds.)
Stage IIIA includes: (Any pT/TX, Any N, M1a, S0); (Any pT/TX, Any N, M1a, S1). M1a: Non-regional nodal or pulmonary metastasis. S0: Marker study levels within normal limits. S1: LDH less than 1.5 x N (N indicates the upper limit of normal for the LDH assay) and hCG less than 5,000 and AFP less than 1,000. (AJCC 6th and 7th eds.)
Stage IIIB includes: (Any pT/TX, N1-3, M0, S2); (Any pT/TX, Any N, M1a, S2). N1: Metastasis with a lymph node mass 2 cm or less in greatest dimension; or multiple lymph nodes, none more than 2cm in greatest dimension. N2: Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, any one mass greater than 2 cm but not more than 5 cm in greatest dimension. N3: Metastasis with a lymph node mass more than 5 cm in greatest dimension. M0: No distant metastasis. M1a: Non-regional nodal or pulmonary metastasis. S2: LDH 1.5-10 x N (N indicates the upper limit of normal for the LDH assay) or hCG 5,000-50,000 or AFP 1,000-10,000. (AJCC 6th and 7th eds.)
Stage IIIC includes: (Any pT/TX, N1-3, M0, S3); (Any pT/TX, Any N, M1a, S3); (Any pT/TX, Any N, M1b, Any S). N1: Metastasis with a lymph node mass 2 cm or less in greatest dimension; or multiple lymph nodes, none more than 2cm in greatest dimension. N2: Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, any one mass greater than 2 cm but not more than 5 cm in greatest dimension. N3: Metastasis with a lymph node mass more than 5 cm in greatest dimension. M0: No distant metastasis. M1a: Non-regional nodal or pulmonary metastasis. M1b: Distant metastasis other than to non-regional lymph nodes and lung. S3: LDH more than 10 x N (N indicates the upper limit of normal for the LDH assay) or hCG more than 50,000 or AFP more than 10,000. (AJCC 6th and 7th eds.)
Stage IS includes: Any pT/TX, N0, M0, S1-3. pTX: Primary tumor cannot be assessed. N0: No regional lymph node metastasis. M0: No distant metastasis. S1: LDH less than 1.5 x N (N indicates the upper limit of normal for the LDH assay) and hCG less than 5,000 and AFP less than 1,000. S2: LDH 1.5-10 x N or hCG 5,000-50,000 or AFP 1,000-10,000. S3: LDH more than 10 x N or hCG more than 50,000 or AFP more than 10,000. (AJCC 6th and 7th eds.)
A disorder characterized by an infectious process involving the scrotum.
Cerebroretinal microangiopathy with calcifications and cysts (CRMCC), also known as Coats plus syndrome, is an autosomal recessive pleomorphic disorder characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline. Patients also have retinal telangiectasia and exudates (Coats disease) as well as extraneurologic manifestations, including osteopenia with poor bone healing and a high risk of gastrointestinal bleeding and portal hypertension caused by vasculature ectasias in the stomach, small intestine, and liver. Some individuals also have hair, skin, and nail changes, as well as anemia and thrombocytopenia (summary by Anderson et al., 2012 and Polvi et al., 2012). Leukoencephalopathy, brain calcifications, and cysts (LCC), also known as Labrune syndrome (614561), has similar central nervous system features as CRMCC in the absence of extraneurologic or systemic manifestations. Although Coats plus syndrome and Labrune syndrome were initially thought to be manifestations of the same disorder, namely CRMCC, molecular evidence has excluded mutations in the CTC1 gene in patients with Labrune syndrome, suggesting that the 2 disorders are not allelic (Anderson et al., 2012; Polvi et al., 2012). Some features of CRMCC resemble those observed in dyskeratosis congenita (see, e.g., 127550), which is a clinically and genetically heterogeneous telomere-related genetic disorder. Genetic Heterogeneity of Cerebroretinal Microangiopathy With Calcifications And Cysts See also CRMCC2 (617341), caused by mutation in the STN1 gene (613128) on chromosome 10q24.
An autosomal recessive condition caused by mutation(s) in the CNTNAP2 gene, encoding contactin-associated protein-like 2. It is characterized by normal development until the onset of intractable focal seizures at age 1-9. After the onset of seizures, language regression, intellectual disability, hyperactivity, and impulsive behaviors begin to occur. The majority of children eventually fulfill the criteria for autism spectrum disorder.
A clustering of abdominal obesity, high triglycerides, low levels of high density lipoprotein cholesterol (HDLC), high blood pressure, and elevated fasting glucose levels is sometimes called metabolic syndrome X (Reaven, 1988) or abdominal obesity-metabolic syndrome (Bjorntorp, 1991). The syndrome may affect nearly 1 in 4 U.S. adults and is considered a veritable epidemic (Ford et al., 2002). It is a major risk factor for both diabetes mellitus (see 125853 and Haffner et al., 1992) and cardiovascular disease (Isomaa et al., 2001). The etiology is complex, determined by the interplay of both genetic and environmental factors. The prevalence varies substantially among ethnic groups, with the highest rates in Mexican American women (Park et al., 2003). Other factors influencing the metabolic syndrome include age, smoking, alcohol, diet, and physical inactivity. Genetic Heterogeneity of Abdominal Obesity-Metabolic Syndrome AOMS2 (605572) has been mapped to chromosome 17p12. AOMS3 (615812) is caused by mutation in the DYRK1B gene (604556) on chromosome 19q13.
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the mandible. []
The orally bioavailable mesylate salt of a synthetic prodrug targeting the human heat-shock protein 90 (Hsp90) with potential antineoplastic activity. Although the mechanism of action remains to be fully elucidated, Hsp90 inhibitor SNX-5422 is rapidly converted to SNX-2112, which accumulates more readily in tumors relative to normal tissues. SNX-2112 inhibits Hsp90, which may result in the proteasomal degradation of oncogenic client proteins, including HER2/ERBB2, and the inhibition of tumor cell proliferation. Hsp90 is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation or immune responses.
A neurological disorder characterized by recurring seizures presenting within the first three months of life and progressive cerebral dysfunction.
A clay compound consisting of aluminosilicate and calcium ions with potential antidiarrheal activity. Calcium aluminosilicate anti-diarrheal consists of microscopically large flat plates of aluminosilicate separated by calcium ions that may sorb toxic chemotherapeutic drugs and their metabolites and inflammatory proteins such as TNF-alpha, which may help minimize chemotherapy-mediated or radiation therapy-mediated damage to the intestinal epithelium and so therapy-related diarrhea.
Pseudo-TORCH syndrome-1 is an autosomal recessive neurologic disorder with characteristic clinical and neuroradiologic features that mimic intrauterine TORCH infection in the absence of evidence of infection. Affected individuals have congenital microcephaly, intracranial calcifications, severe developmental delay, simplified gyration and polymicrogyria, and severe developmental delay (Reardon et al., 1994; O'Driscoll et al., 2010). Crow et al. (2000, 2003) called attention to the phenotypic overlap of pseudo-TORCH syndrome and Aicardi-Goutieres syndrome (AGS; 225750), and even suggested that some cases may represent the same disorder. Congenital microcephaly, thrombocytopenia, hepatic dysfunction, and hepatosplenomegaly are usually associated with pseudo-TORCH syndrome and not with AGS, but some patients with AGS have shown these features. Genetic Heterogeneity of Pseudo-TORCH Syndrome See also PTORCH2 (617397), caused by mutation in the USP18 gene (607057) on chromosome 22q11.
Fragile X-associated primary ovarian insufficiency (FXPOI) is a condition that affects women and is characterized by reduced function of the ovaries. The ovaries are the female reproductive organs in which egg cells are produced. As a form of primary ovarian insufficiency, FXPOI can cause irregular menstrual cycles, early menopause, an inability to have children (infertility), and elevated levels of a hormone known as follicle stimulating hormone (FSH). FSH is produced in both males and females and helps regulate the development of reproductive cells (eggs in females and sperm in males). In females, the level of FSH rises and falls, but overall it increases as a woman ages. In younger women, elevated levels may indicate early menopause and fertility problems.The severity of FXPOI is variable. The most severely affected women have overt POI (formerly called premature ovarian failure). These women have irregular or absent menstrual periods and elevated FSH levels before age 40. Overt POI often causes infertility. Other women have occult POI; they have normal menstrual periods but reduced fertility, and they may have elevated levels of FSH (in which case, it is called biochemical POI). The reduction in ovarian function caused by FXPOI results in low levels of the hormone estrogen, which leads to many of the common signs and symptoms of menopause, such as hot flashes, insomnia, and thinning of the bones (osteoporosis). Women with FXPOI undergo menopause an average of 5 years earlier than women without the condition.
A synthetic, small molecule inhibitor of the BET (Bromodomain and Extra-Terminal) family of bromodomain-containing proteins 2, 3 and 4 with potential antineoplastic activity. Upon administration, birabresib binds to the acetylated lysine recognition motifs on the bromodomain of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histone peptides. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes, including c-Myc-dependent target genes, may lead to an inhibition of tumor cell growth. Characterized by a tandem repeat of bromodomain at the N-terminus, the BET proteins BRD2, BRD3, BRD4 are transcriptional regulators that play an important role in cellular growth.
Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmentation, usually in a flexural distribution. However, generalized DDD can also occur, with numerous hypopigmented or erythematous macules and papules on the neck, chest, and abdomen. The histopathology of DDD shows characteristic thin branch-like patterns of epidermal downgrowth (summary by Li et al., 2013). Review of Reticulate Pigment Disorders Muller et al. (2012) reviewed the spectrum of reticulate pigment disorders of the skin, tabulating all reported cases of patients with Dowling-Degos disease, reticulate acropigmentation of Kitamura (RAK; 615537), reticulate acropigmentation of Dohi (RAD; 127400), Galli-Galli disease (GGD), and Haber syndrome (HS). Of 82 cases, 26 (31.7%) were clinically diagnosed as DDD, 13 (15.9%) as RAD, 11 (13.4%) as GGD, 8 (9.8%) as RAK, and 8 (9.8%) as HS; in addition, 16 (19.5%) of the cases showed overlap between DDD and RAK. Muller et al. (2012) also published photographs of an affected individual exhibiting an overlap of clinical features of DDD, GGD, RAD, and RAK. The authors noted that in reticulate disorders of the skin, the main disease entity is DDD, with a subset of cases exhibiting acantholysis (GGD), facial erythema (HS), or an acral distribution (RAD; RAK). Muller et al. (2012) concluded that all reticulate pigment diseases of the skin are varying manifestations of a single entity. Genetic Heterogeneity of Reticulate Pigment Disorders Dowling-Degos disease-2 (DDD2; 615327) is caused by mutation in the POFUT1 gene (607491) on chromosome 20q11. Dowling-Degos disease-3 (DDD3; 615674) has been mapped to chromosome 17p33.3. Dowling-Degos disease-4 (DDD4; 615696) is caused by mutation in the POGLUT1 gene (615618) on chromosome 3q13. Dyschromatosis symmetrica hereditaria (DSH; 127400), also known as reticulate acropigmentation of Dohi (RAD), is caused by mutation in the ADAR gene (146920) on chromosome 1q21. Reticulate acropigmentation of Kitamura (RAK; 615537) is caused by mutation in the ADAM10 gene (602192) on chromosome 15q21.
An electrocardiographic finding of a ventricular tachycardia in which the QRS complexes have a variable morphology and often rate. (CDISC)
A hamartomatous skin lesion containing sebaceous glands. It is usually located in the scalp.
Patients and families with a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) or the EPCAM gene but who have not met the criteria for hereditary nonpolyposis colon cancer.
A semi-synthetic, orally bioavailable, third-generation taxane derivative and microtubule-stabilizing agent, with potential antineoplastic activity. Upon administration, simotaxel binds to tubulin, promotes microtubule assembly and stabilization, and prevents microtubule depolymerization. This results in G2/M arrest, apoptosis and the inhibition of cell proliferation in susceptible tumor cells. This agent is a poor substrate for P-glycoprotein-related drug resistance mechanisms; therefore, it may be useful for treating multi-drug resistant tumors. MST-997 is more potent than paclitaxel and docetaxel and overcomes paclitaxel and docetaxel resistance in certain tumor cell types.
A Number 0 Tessier cleft is a true median cleft lip with a broad columella and bifid nasal tip. The alveolar cleft is between the central incisors. The nasal septum may be thickened, duplicated, or absent. The nasal bridge is usually broad with associated orbital hypertelorism. The midline soft tissue anomaly may range from a mild broadening of the philtrum or there may be a true median cleft lip. The columella and nasal tip are typically bifid and broadened with a midline depression. The alae nasi are intact but laterally displaced. The nose appears shortened in the vertical dimension. [PMID:2503273]
This midline cranial cleft usually occurs with a midline facial cleft that completes a median craniofacial dysraphia. A broad nasal root and bifid nose are associated with orbital hypertelorism and a median frontal encephalocele. The frontal bone abnormality varies from a minor flattening to a large midline defect. There is an increased distance between the olfactory grooves. The crista galli is widened, duplicated, or in some cases absent. Marked inferior prolapse of the enlarged ethmoid bone occurs with orbital hypertelorism. The severe orbital hypertelorism is associated with a broad flattening of the glabella and extreme lateral displacement of the inner canthi. The periorbita, including the eyelids and eyebrows, are otherwise normal. A long midline projection of the frontal hairline marks the superior extent of the soft tissue features of this midline cranial cleft. The median frontal defect delineates the region through which the frontal encephalocele herniates. The lateral segments of the frontal bone sweep upward from the region of the intact glabella and are flattened laterally. No pneumatization of the frontal sinus is evident. The crista galli and the perpendicular plate of the ethmoid are bifid. Just as the ethmoid, including the cribriform plate, is widened and caudally displaced, the sphenoid sinus is broadened and extensively, but symmetrically pneumatized. The lateral rotation of the greater and lesser wings of the sphenoid results in a relative shortening of the anteroposterior dimension of the middle cranial fossa. The floor of the anterior cranial fossa is upslanting from its medial aspect to its lateral aspect, with a harlequin appearance on the coronal scan. [PMID:2503273]
The temporozygomatic Number 7 cleft is found in both Treacher Collins syndrome and hemifacial microsomia. Soft tissue manifestations include macrostomia, malformations of the external and middle ear, temporalis muscle, variable involvement of the seventh cranial nerve (in hemifacial microsomia), and abnormalities of the preauricular hair in Treacher Collins syndrome. The skeletal cleft is through the pterygomaxillary junction, and vertical maxillary hypoplasia is present. In addition, abnormality of the mandibular ramus, coronoid, and condyle and absence of the zygomatic arch are typically present. A soft tissue furrow extends from the macrostomia laterally and superiorly across the cheek toward the preauricular hairline. The lower eyelids are intact. The anatomy of the external ear is normal, and there are no preauricular tags. Bony clefting is through the pterygomaxillary junction with hypoplasia of the alveolar process in the molar region, thereby producing a posterior open bite. The maxilla is hypoplastic, although the maxillary sinuses are symmetrically pneumatized. The hypoplastic zygomatic body arches upward, but then it takes a downward course and is severely malformed and displaced. The zygoma is continuous posteriorly with an apparently normal zygomatic process of the temporal bone. The mandibular condyle and coronoid process are hypoplastic and asymmetric. There is no antegonial notching of the mandible. Marked cranial base asymmetry, with tilting and asymmetric positioning of the temporomandibular articulations, is present. The anatomy of the sphenoid is abnormal, especially on the right where there is no recognizable medial or lateral pterygoid plate. [PMID:2503273]
A facial cleft extending from the zygomatic arch to the eye. This zygomaticomaxillary cleft is similar to that typically found in Treacher Collins syndrome. The overlying tissue shows a vertical sclerodermic furrow radiating from the labial commissure or the angle of the mandible across the cheek to a coloboma of the lower eyelid between the middle and lateral one-third. Microphthalmia is not observed. The skeletal cleft is between the maxilla and zygoma; it passes through the inferolateral orbital rim to enter the inferior orbital fissure. No alveolar cleft is present. The zygomatic arch is intact. The soft tissue furrow, which is more apparent on the right, radiates from the oral commissure toward the lateral two-thirds of the lower eyelid. The antimongoloid obliquity of the palpebral fissures is associated with laterally placed lower eyelid clefts and some ectropion. Aleft-sided anophthalmia is accompanied by adjacent soft tissue hypoplasia and is reflected in a short palpebral fissure, enophthalmos, and minor ptosis of the eyebrow. No abnormality is present in the alveolar arch except for some tilting of the occlusal plane secondary to hypoplasia of the left side of the maxilla. There is a vertical bony groove in the region of the zygomaticomaxillary suture that ends in the inferolateral portion of a small bony orbit. More laterally, the remainder of the zygomatic body and arch is normal in both shape and dimension. The lateral orbital floor is downslanting but intact, and it lacks direct communication with the temporal or infratemporal fossae. The hypoplasia of the left side of the maxilla and orbit is associated with a reduction in the transverse and anteroposterior dimensions of the anterior cranial fossa; mild asymmetry of the middle cranial fossa and calvarium is present. No significant asymmetry of size, shape, or position is present in the sphenoid. [PMID:2503273]
The frontozygomatic or Number 8 cleft is found in both Treacher Collins syndrome and the Goldenhar variant of hemifacial microsomia. Skeletal defects are more prominent in Treacher Collins syndrome, whereas the soft tissue clefting is more typical in cases of ''Goldenhar syndrome''. Soft tissue clefting presents as a dermatocele, a true lateral eyelid coloboma with absence of the outer canthus, and anomalies of the globe itself, especially epibulbar cysts in patients with Goldenhar syndrome. The frontozygomatic bony cleft produces absence of the lateral orbital rim; this border now is formed by the hypoplastic greater wing of the sphenoid. The absence of bony support for the outer canthus produces lateral canthal dystopia and the characteristic antimongoloid slant of the palpebral fissures. Secondary to the bony deficiency in the lateral orbital wall and floor, there is soft tissue continuity between the orbit, temporal fossa, and infratemporal region. Preauricular hairline indicators delineate the Number 8 cleft as the first of the northbound clefts. Complete absence of the bony lateral orbital wall and rim constitute the skeletal element of the Number 8 cleft. The lateral border of the orbit is formed by the greater wing of the sphenoid from which small spicules of bone, which represent the rudimentary zygoma, may be found in Treacher Collins syndrome. The symmetry of the facial anomalies is reflected in the apparently normal symmetric anterior and middle cranial fossae. [PMID:2503273]
Classic Ehlers-Danlos syndrome (cEDS) is a connective tissue disorder characterized by skin hyperextensibility, atrophic scarring, and generalized joint hypermobility (GJH). The skin is soft and doughy to the touch, and hyperextensible, extending easily and snapping back after release (unlike lax, redundant skin, as in cutis laxa). The skin is fragile, as manifested by splitting of the dermis following relatively minor trauma, especially over pressure points (knees, elbows) and areas prone to trauma (shins, forehead, chin). Wound healing is poor, and stretching of scars after apparently successful primary wound healing is characteristic. Complications of joint hypermobility, such as dislocations of the shoulder, patella, digits, hip, radius, and clavicle, usually resolve spontaneously or are easily managed by the affected individual. Other features include hypotonia with delayed motor development, fatigue and muscle cramps, and easy bruising. Mitral valve prolapse can occur infrequently, but tends to be of little clinical consequence. Aortic root dilatation has been reported, appears to be more common in young individuals, and rarely progresses.
Typical absences are brief for seconds generalized epileptic seizures of abrupt onset and abrupt termination with impairment of consciousness. [HPO:jalbers]
A disorder characterized by the acute loss of renal function (within 2 weeks) and is traditionally classified as pre-renal (low blood flow into kidney), renal (kidney damage) and post-renal causes (ureteral or bladder outflow obstruction).
A change in the nucleotide sequence of the ATRX gene.
A preparation of allogeneic or autologous cells that is meant to be administered to a patient and may have a therapeutic effect.
A disorder characterized by bleeding from the cecum.
A disorder characterized by an infectious process involving the cecum.
A disorder characterized by a necrotic process occurring in the brain and/or spinal cord.
Cervical carcinoma confined to uterus (extension to corpus should be disregarded). (from AJCC 8th Ed.)
Cervical cancer with clinically visible lesion confined to the cervix. (from AJCC 8th Ed.)
Cervical cancer with clinically visible lesion confined to the cervix or microscopic lesion greater than T1a/IA2. It includes all macroscopically visible lesions, even those with superficial invasion. (from AJCC 8th Ed.)
Cervical cancer with clinically visible lesion 4.0 cm or less in greatest dimension. (from AJCC 8th Ed.)
Cervical cancer with clinically visible lesion more than 4.0 cm in greatest dimension. (from AJCC 8th Ed.)
Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina. (from AJCC 8th Ed.)
Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina without parametrial invasion. (from AJCC 8th Ed.)
Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina without parametrial invasion. Clinically visible lesion 4.0 cm or less in greatest dimension. (from AJCC 8th Ed.)
Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina without parametrial invasion. Clinically visible lesion more than 4.0 cm in greatest dimension. (from AJCC 8th Ed.)
A disorder characterized by an infectious process involving a mucosal surface.
A disorder characterized by ulceration or inflammation of the oral mucosal.
A disorder characterized by progressive deterioration of the lungs, liver, kidney and clotting mechanisms.
A disorder characterized by marked cramping sensation originating from a muscle or group of muscles.
A disorder characterized by a reduction in the strength of the muscles on the left side of the body.
A disorder characterized by a reduction in the strength of the lower limb muscles.
A disorder characterized by a reduction in the strength of the muscles on the right side of the body.
A disorder characterized by a reduction in the strength of the trunk muscles.
A disorder characterized by a reduction in the strength of the upper limb muscles.
A disorder characterized by a malformation of the musculoskeletal system.
A disorder characterized by marked discomfort sensation originating from a muscle or group of muscles.
A disorder characterized by weakness and rapid fatigue of any of the skeletal muscles.
A disorder characterized by the formation of crystals/kidney stones in the pelvis of the kidney.
A disorder characterized by paroxysmal and severe flank marked discomfort radiating to the inguinal area. Often, the cause is the passage of crystals/kidney stones.
A disorder characterized by impaired gas exchange by the respiratory system resulting in hypoxia and a decrease in oxygenation of the tissues that may be associated with an increase in arterial levels of carbon dioxide.
A disorder characterized by the separation of the inner retina layers from the underlying pigment epithelium.
A disorder characterized by a small laceration of the retina, this occurs when the vitreous separates from the retina. Symptoms include flashes and floaters.
A disorder characterized by pathological retinal blood vessels that adversely affects vision.
A disorder characterized by bleeding from the retroperitoneal area.
A disorder characterized by headaches, mental status changes, visual disturbances, and/or seizures associated with imaging findings of posterior leukoencephalopathy. It has been observed in association with hypertensive encephalopathy, eclampsia, and immunosuppressive and cytotoxic drug treatment. It is an acute or subacute reversible condition. Also known as posterior reversible encephalopathy syndrome (PRES).
A disorder characterized by the breakdown of muscle tissue resulting in the release of muscle fiber contents into the bloodstream.
A disorder characterized by an infectious process involving the nasal mucosal.
A disorder characterized by excessive mucous secretions draining from the nose.
A disorder characterized by an infectious process involving the pleura.
A disorder characterized by a sensation of marked discomfort in the pleura.
A disorder characterized by inflammation focally or diffusely affecting the lung parenchyma.
A disorder characterized by an increase in blood pressure in the portal venous system.
A disorder characterized by the formation of a thrombus (blood clot) in the portal vein.
A disorder characterized by bleeding occurring after a surgical procedure.
A finding of a previously undocumented problem that occurs after a thoracic procedure.
Stage I includes: T1, N0, M0. T1: Ovarian cancer with tumor limited to ovaries (one or both). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage I includes: T1a, N0, M0. T1a: Penile cancer with tumor without lymphovascular invasion or perineural invasion and is not high grade (i.e., grade 3 or sarcomatoid). N0: No lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: (cT1a-c, cT2a, N0, M0, PSA less than 10, Grade Group 1); (pT2, N0, M0, PSA less than 10, Grade Group 1). cT1a: Prostate cancer in which the tumor is an incidental histologic finding in 5% or less of tissue resected. cT1b: Prostate cancer in which the tumor is an incidental histologic finding in more than 5% of tissue resected. cT1c: Prostate cancer in which the tumor is identified by needle biopsy found in one or both sides, but not palpable. cT2a: Prostate cancer in which the tumor involves one-half of one side or less. pT2: Prostate cancer which is organ confined. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 1: Gleason Score 6 or less, Gleason Pattern 3 or less+3. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor measuring 7 cm or less in greatest dimension, limited to the kidney. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Tumor invades subepithelial connective tissue. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: Under 55 years: Any T, Any N, M0. 55 years and older: (T1, N0/NX, M0); (T2, N0/NX, M0). T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but 4 cm or less in greatest dimension limited to the thyroid. N0: No evidence of locoregional lymph node metastasis. NX: Regional lymph nodes cannot be assessed. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. N0: No evidence of locoregional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: For male penile urethra and female urethra: Tumor invades subepithelial connective tissue. For prostatic urethra: Tumor invades urethral subepithelial connective tissue immediately underlying the urothelium. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: T1, N0, M0. T1: Uterine corpus carcinoma or carcinosarcoma with tumor confined to the corpus uteri, including endocervical glandular involvement. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage I includes: IA: T1a, N0, M0; IB: T1b, N0, M0. T1a: Tumor confined to the vagina, measuring 2.0 cm or less. T1b: Tumor confined to the vagina, measuring more than 2.0 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IA includes: T1a, Any N, M0. T1a: Tumor diagnosed only by microscopy. Stromal invasion with a maximum depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less. Vascular space involvement, venous or lymphatic, does not affect classification. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IA includes: T1a, N0, M0. T1a: Fallopian tube cancer with tumor limited to fallopian tube surface; no malignant cells in ascites or peritoneal washings N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IA includes: T1a, N0, M0. T1a: Ovarian cancer with tumor limited to one ovary (capsule intact); no malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IA includes: T1a, N0, M0. T1a: Uterine corpus carcinoma or carcinosarcoma with tumor limited to the endometrium or invading less than half the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IA1 includes: T1a1, Any N, M0. T1a1: Invasive cervical carcinoma with measured stromal invasion of 3.0 mm or less in depth and 7.0 mm or less in horizontal spread. M0: No distant metastasis. (AJCC 8th Ed.)
A disorder characterized by a sensation of marked discomfort in the external ear region.
A disorder characterized by apprehension of danger and dread accompanied by restlessness, tension, tachycardia, and dyspnea unattached to a clearly identifiable stimulus.
A disorder characterized by an infectious process involving the skin such as cellulitis.
A disorder characterized by a sensation of marked discomfort in the tooth.
A disorder characterized by uncontrolled and purposeless movements.
A disorder characterized by an infectious process involving the soft tissues around the nail.
A disorder characterized by elevation of the body's temperature above the upper limit of normal.
A disorder characterized by the abnormal absence of menses for at least three consecutive menstrual cycles
A disorder characterized by delivery of a viable infant before the normal end of gestation. Typically, viability is achievable between the twentieth and thirty-seventh week of gestation.
A disorder characterized by occlusion of the hepatic veins and typically presents with abdominal pain, ascites and hepatomegaly.
A disorder characterized by non-neoplastic overgrowth of bone.
A disorder characterized by marked discomfort in the throat
A disorder characterized by an abnormal increase in the curvature of the thoracic portion of the spine.
A disorder characterized by excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behavior and elevation of mood.
A loss of PREGNANCY from natural causes before the 20th week of pregnancy. (2017/18 ICD-10-CM)
A disorder characterized by a malformed, lateral curvature of the spine.
A disorder characterized by a sensation of marked discomfort related to a limb or an organ that is removed from or is not physically part of the body.
Death that cannot be attributed to a CTCAE term associated with Grade 5.
A finding of traumatic injury to the hip in which the continuity of either the femoral head, femoral neck, intertrochanteric or subtrochanteric regions is broken.
A disorder characterized by an increase in amounts of fluid within the pleural cavity. Symptoms include shortness of breath, cough and marked chest discomfort.
A disorder characterized by a sensation of marked discomfort of the lip.
The presence of mutations in both alleles of the ATM gene that either lead to loss of expression of the ATM protein or result in the translation of an inactive ATM protein.
A disorder characterized by a rupture in the wall of the extrahepatic or intrahepatic bile duct.
A disorder characterized by occlusion of a vessel by a thrombus that has migrated from a distal site via the blood stream.
A disorder characterized by an incomplete paralysis of the muscles of the stomach wall resulting in delayed emptying of the gastric contents into the small intestine.
Death due to disease progression that cannot be attributed to a CTCAE term associated with Grade 5.
A disorder characterized by an infectious process involving the gallbladder.
A disorder characterized by an abnormal responsiveness to stimuli or physiological arousal; may be in response to pain, fright, a drug, an emotional situation or a medical condition.
A disorder characterized by a reduction in the strength of muscles in multiple anatomic sites.
A disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or hypoxia caused by the release of cytokines.
A disorder characterized by an abnormal communication between the bile ducts and another organ or anatomic site.
A disorder characterized by abnormal function or appearance of the testis.
A disorder characterized by an abnormal communication between the bronchus and another organ or anatomic site.
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, alkaline phosphatase, aminotransferase, and/or prolongation of prothrombin time (INR.) Drug-induced liever injury (DILI) as defined by Hy's Law.
A disorder characterized by bleeding from the gastric wall.
A disorder characterized by abnormally high acidity (high hydrogen-ion concentration) of the blood and other body tissues.
A disorder characterized by underdevelopment of the breast.
A disorder characterized by inflammation or infection of the hair follicles.
A disorder characterized by a narrowing of the lumen of the pancreatic duct.
A disorder characterized by an infectious process involving a joint.
A disorder characterized by a necrotic process occurring in the soft tissues of the lower extremity.
A disorder characterized by blockage of the normal flow of the contents in the stomach.
A disorder characterized by vertical or horizontal ridges on the nails.
A finding of damage to the superior vena cava.
A disorder characterized by a narrowing of the lumen of the small intestine.
A finding of leakage due to breakdown of a pharyngeal anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by an infectious process involving the vulva.
A finding of leakage of urine due to breakdown of a bladder anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by laboratory test results that indicate an elevation in the concentration of blood sugar. It is usually an indication of diabetes mellitus or glucose intolerance.
A disorder characterized by a sensation of marked discomfort in the liver region.
A disorder characterized by the presence of a virus in the blood stream.
A disorder characterized by the presence of pathogenic microorganisms in the blood stream that cause a rapidly progressing systemic reaction that may lead to shock.
A disorder characterized by bleeding from the intestinal stoma.
A disorder characterized by laboratory test results that indicate a low concentration of magnesium in the blood.
A disorder characterized by the body's immune system attacking the peripheral nervous system causing ascending paralysis.
A disorder characterized by an infectious process involving the upper respiratory tract (nose, paranasal sinuses, pharynx, larynx, or trachea).
A disorder characterized by laboratory test results that indicate an elevation in the concentration of calcium (corrected for albumin) in blood.
A disorder characterized by inflammation involving a joint.
A disorder characterized by an abnormal communication between the opening in the anal canal to the perianal skin.
A disorder characterized by partial or complete loss of the ability to detect or understand sounds resulting from damage to ear structures.
A disorder characterized by an infectious process involving the kidney.
A finding based on laboratory test results that indicate an increase in the level of lipase in a biological specimen.
A disorder characterized by a state of restlessness associated with unpleasant feelings of irritability and tension.
A disorder characterized by an uncomfortable feeling of inner restlessness and inability to stay still; this is a side effect of some psychotropic drugs.
A finding based on laboratory test results that indicate an increase in the level of alanine aminotransferase (ALT or SGPT) in the blood specimen.
A disorder characterized by an increase in sensitivity to the adverse effects of alcohol, which can include nasal congestion, skin flushes, heart dysrhythmias, nausea, vomiting, indigestion and headaches.
A disorder characterized by abnormally high alkalinity (low hydrogen-ion concentration) of the blood and other body tissues.
A disorder characterized by an adverse local or general response from exposure to an allergen.
A disorder characterized by an inflammation of the nasal mucous membranes caused by an IgE-mediated response to external allergens. The inflammation may also involve the mucous membranes of the sinuses, eyes, middle ear, and pharynx. Symptoms include sneezing, nasal congestion, rhinorrhea and itching.
Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina with parametrial invasion. (from AJCC 8th Ed.)
Cervical cancer extending to pelvic sidewall and/or involving the lower third of vagina, and/or causing hydronephrosis or nonfunctioning kidney. The pelvic sidewall is defined as the muscle, fascia, neurovascular structures, and skeletal portions of the bony pelvis. (from AJCC 8th Ed.)
Cervical cancer involving the lower third of vagina but not extending to pelvic wall. (from AJCC 8th Ed.)
Cervical cancer extending to pelvic wall and/or causing hydronephrosis or nonfunctioning kidney. (from AJCC 8th Ed.)
Cervical cancer invading the mucosa of the bladder or rectum, and/or extending beyond the true pelvis (bullous edema is not sufficient to classify a tumor as T4). (from AJCC 8th Ed.)
Cervical cancer with distant metastasis (including peritoneal spread or involvement of the supraclavicular, mediastinal, or distant lymph nodes; lung; liver; or bone). (from AJCC 8th Ed.)
A disorder characterized by an infectious process involving the uterine cervix.
A disorder characterized by insufficiently healthy hematapoietic cell production by the bone marrow.
A disorder characterized by inflammation of the muscle tissue of the heart.
A disorder characterized by inflammation involving the skeletal muscles.
A disorder characterized by a change in the nails.
A disorder characterized by a change in the color of the nail plate.
A disorder characterized by an infectious process involving the nail.
A disorder characterized by loss of all or a portion of the nail.
A finding of damage to the jugular vein.
A disorder characterized by a sudden contraction of the smooth muscles of the bronchial wall.
A disorder characterized by the presence of macules (flat) and papules (elevated). Also known as morbillform rash, it is one of the most common cutaneous adverse events, frequently affecting the upper trunk, spreading centripetally and associated with pruritis.
A disorder characterized by a decrease in consciousness characterized by mental and physical inertness.
A disorder characterized by swelling due to an excessive accumulation of fluid in the genitals.
A disorder characterized by hemorrhagic areas of the skin and mucous membrane. Newer lesions appear reddish in color. Older lesions are usually a darker purple color and eventually become a brownish-yellow color.
A disorder characterized by unusually early development of secondary sexual features; the onset of sexual maturation begins usually before age 8 for girls and before age 9 for boys.
A disorder characterized by premature ovarian failure. Symptoms may include hot flashes, night sweats, mood swings, and a decrease in sex drive. Laboratory findings include elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH.)
A disorder characterized by an episode of lightheadedness and dizziness which may precede an episode of syncope.
Stage IA2 includes: T1a2, Any N, M0. T1a2: Invasive cervical carcinoma with measured stromal invasion of more than 3.0 mm and not more than 5.0 mm, with a horizontal spread of 7.0 mm or less. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB includes: T1b, Any N, M0. T1b: Tumor with clinically visible lesion confined to the cervix or microscopic lesion greater than T1a/IA2. It includes all macroscopically visible lesions, even those with superficial invasion. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB includes: T1b, N0, M0. T1b: Fallopian tube cancer with tumor limited to fallopian tubes; no tumor on fallopian tube surface; no malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB includes: T1b, N0, M0. T1b: Ovarian cancer with tumor limited to one or both ovaries (capsules intact); no tumor on ovarian surface; no malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB includes: T1b, N0, M0. T1b: Uterine corpus carcinoma or carcinosarcoma with tumor invading one half or more of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB1 includes: T1b1, Any N, M0. T1b1: Tumor with clinically visible lesion 4.0 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB2 includes: T1b2, Any N, M0. T1b2: Tumor with clinically visible lesion more than 4.0 cm in greatest dimension. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IC includes: T1c, N0, M0. T1c: Fallopian tube cancer with tumor limited to fallopian tubes, with any of the following: surgical spill, capsule ruptured before surgery or tumor on fallopian tube surface, or malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IC includes: T1c, N0, M0. T1c: Ovarian cancer with tumor limited to one or both ovaries, with any of the following: surgical spill, capsule ruptured before surgery or tumor on ovarian surface, or malignant cells in ascites or peritoneal washings. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Tumor measuring more than 5 cm in greatest dimension, with no extra-adrenal invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage II includes: (T2a, N0, M0); (T2b, N0, M0). T2a: Tumor invades superficial muscularis propria (inner half). T2b: Tumor invades deep muscularis propria (outer half). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, Any N, M0. T2: Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: Under 55 years: Any T, Any N, M1; 55 years and older: (T1, N1, M0); (T2, N1, M0); (T3a/T3b, Any N, M0). T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but 4 cm or less in greatest dimension limited to the thyroid. T3a: Tumor measuring more than 4 cm in greatest dimension limited to the thyroid. T3b: Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles) from a tumor of any size. N1: Metastasis to regional nodes. M0: No distant metastasis. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Fallopian tube cancer with tumor involving fallopian tubes with pelvic extension below pelvic brim. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
A disorder characterized by expectorated secretions upon coughing.
Newborn death occurring during the first 28 days after birth.
A disorder characterized by an infectious process involving the brain and spinal cord tissues.
A disorder characterized by the acute and sudden development of confusion, illusions, movement changes, inattentiveness, agitation, and hallucinations. Usually, it is a reversible condition.
A disorder characterized by a rupture in the colonic wall.
A disorder characterized by an infectious process involving a tooth.
A disorder characterized by greater growth than expected for age.
A disorder characterized by an infectious process involving the skeletal muscles.
A disorder characterized by inflammation of the skin characterized by the presence of bullae which are filled with fluid.
A disorder characterized by involvement of the optic nerve (second cranial nerve).
A disorder characterized by an infectious process involving the lungs, including pneumonia.
A disorder characterized by dysfunction of the corticospinal (pyramidal) tracts of the spinal cord. Symptoms include an increase in the muscle tone in the lower extremities, hyperreflexia, positive Babinski and a decrease in fine motor coordination.
A finding based on laboratory test results that indicate a decrease in number of lymphocytes in a blood specimen.
A disorder characterized by blockage of the normal flow of contents of the urinary tract.
A disorder characterized by pathological irregularities in the cardiac conduction system.
A disorder characterized by a narrowing of the bronchial tube.
A disorder characterized by a decrease in flexibility of a cervical spine joint.
A finding of leakage due to breakdown of a ureteral anastomosis (surgical connection of two separate anatomic structures).
A finding of leakage due to breakdown of an anastomosis (surgical connection of two separate anatomic structures) in the small bowel.
A disorder characterized by gross necrosis of the myocardium; this is due to an interruption of blood supply to the area.
A disorder characterized by a sensation of marked discomfort in the ear.
A disorder characterized by a sensation of marked discomfort in the gingival region.
A finding based on laboratory test results that indicate an abnormally high level of bilirubin in the blood. Excess bilirubin is associated with jaundice.
A disorder characterized by shrinking of adipose tissue.
A finding of leakage of bile due to breakdown of a biliary anastomosis (surgical connection of two separate anatomic structures).
A finding of damage to the ear during a surgical procedure.
A disorder characterized by a change in the color of the urine.
A finding based on laboratory test results that indicate a decrease in number of neutrophils in a blood specimen.
A disorder characterized by an uncomfortable, often painful feeling in the stomach, resulting from impaired digestion. Symptoms include burning stomach, bloating, heartburn, nausea and vomiting.
A disorder characterized by an abnormal communication between the uterus and another organ or anatomic site.
A finding of damage to the respiratory system during a surgical procedure.
A disorder characterized by an infectious process involving the bladder.
A disorder characterized by incomplete paralysis of an extraocular muscle.
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the anal canal.
A finding of damage to the ankle joint characterized by a break in the continuity of the ankle bone. Symptoms include marked discomfort, swelling and difficulty moving the affected leg and foot.
A disorder characterized by an abnormal communication between a bronchus and the pleural cavity.
A disorder characterized by an increase in sexual desire.
A disorder characterized by a high pitched breathing sound due to laryngeal or upper airway obstruction.
A disorder characterized by laboratory test results that indicate an elevation in the concentration of potassium in the blood; associated with kidney failure or sometimes with the use of diuretic drugs.
A disorder characterized by an infectious process involving the trachea.
A disorder characterized by a narrowing of the lumen of the colon.
A finding of a cardiac dysrhythmia characterized by an abnormally long corrected QT interval.
A finding based on laboratory test results that indicate an decrease in number of white blood cells in a blood specimen.
A disorder characterized by inappropriate masculinization occurring in a female or prepubertal male.
A disorder characterized by a feeling of general discomfort or uneasiness, an out-of-sorts feeling.
A disorder characterized by a change in the sense of smell.
A disorder characterized by fibrotic degeneration of the deep connective tissues.
A disorder characterized by an infectious process involving the biliary tract.
A disorder characterized by laboratory test results that indicate glucose in the urine.
A disorder characterized by an infectious process involving the esophagus.
A finding based on laboratory test results that indicate increased levels of cardiac troponin T in a biological specimen.
A disorder characterized by redness, marked discomfort, swelling, and tingling in the palms of the hands or the soles of the feet. Also known as Hand-Foot Syndrome.
A finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.
A disorder characterized by an infectious process involving the orbit of the eye.
A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances.
A disorder characterized by ulceration or inflammation of the mucous membrane of the rectum.
A disorder characterized by a decrease or absence of blood supply to the brain caused by obstruction (thrombosis or embolism) of an artery resulting in neurological damage.
A disorder characterized by excessive sweating.
A finding of damage to the spleen during a surgical procedure.
A disorder characterized by the sensation of marked discomfort, distress or agony.
A disorder characterized by damage or dysfunction of the peripheral motor nerves.
A disorder characterized by blockage of the lumen of the trachea.
A disorder characterized by a sensation of marked discomfort in the upper or lower extremities.
A disorder characterized by leakage of intravascular fluids into the extravascular space. This syndrome is observed in patients who demonstrate a state of generalized leaky capillaries following shock syndromes, low-flow states, ischemia-reperfusion injuries, toxemias, medications, or poisoning. It can lead to generalized edema and multiple organ failure.
A disorder characterized by hair density or length beyond the accepted limits of normal in a particular body region, for a particular age or race.
A disorder characterized by a narrowing of the lumen of the ileum.
A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and histamine-like substances from mast cells, causing a hypersensitivity immune response. Clinically, it presents with breathing difficulty, dizziness, hypotension, cyanosis and loss of consciousness and may lead to death.
A disorder characterized by necrotic changes in the bone tissue due to interruption of blood supply. Most often affecting the epiphysis of the long bones, the necrotic changes result in the collapse and the destruction of the bone structure.
A finding based on laboratory test results that indicate a decrease in levels of bicarbonate in a venous blood specimen.
A disorder characterized by bleeding from the bronchial wall and/or lung parenchyma.
A disorder characterized by change in hair color or loss of normal pigmentation.
A disorder characterized by laboratory test results that indicate an elevation in the concentration of uric acid.
A disorder characterized by blockage of the urostomy.
A disorder characterized by a sensation of marked discomfort in the anal region.
A rare syndrome of peripheral and cranial nerve dysfunction in patients with haematologic malignancies, mostly non-Hodgkin's lymphoma or acute leukaemia, characterised by painful or painless involvement of peripheral or cranial nerves or nerve roots. The clinical presentation is diverse depending on the site involved and includes plexopathy, mononeuritis multiplex, peripheral neuropathy, radiculopathy and cranial nerve palsies.
A finding based on laboratory test results that indicate an increase in the level of aspartate aminotransferase (AST or SGOT) in a blood specimen.
A disorder characterized by air in the subcutaneous tissue.
A disorder characterized by an infectious process involving the internal structures of the eye.
A disorder characterized by inflammation involving the vagina. Symptoms may include redness, edema, marked discomfort and an increase in vaginal discharge.
A disorder characterized by an infectious process involving the mediastinum.
A disorder characterized by an infectious process involving the duodenum.
A disorder characterized by excessive tearing in the eyes; it can be caused by overproduction of tears or impaired drainage of the tear duct.
A disorder characterized by a circumscribed and elevated skin lesion filled with pus.
A disorder characterized by a dysrhythmia with complete failure of atrial electrical impulse conduction through the AV node to the ventricles.
A disorder characterized by accumulation of milky fluid in the peritoneal cavity.
A disorder characterized by laboratory test results that indicate increased methemoglobin in the blood.
A disorder characterized by a defect in aortic valve function or structure.
A disorder characterized by dysfunction of the vagus nerve (tenth cranial nerve).
A disorder characterized by cessation of the pumping function of the heart.
A disorder characterized by leakage of the infusion into the surrounding tissue. Signs and symptoms may include induration, erythema, swelling, burning sensation and marked discomfort at the infusion site.
A disorder characterized by distortion of sensory perception, resulting in an abnormal and unpleasant sensation.
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the small intestine.
A disorder characterized by severe hepatic injury as a result of the blood vessels of the liver becoming inflamed and/or blocked.
A disorder characterized by an infectious process involving the outer ear and ear canal. Contributory factors include excessive water exposure (swimmer's ear infection) and cuts in the ear canal. Symptoms include fullness, itching, swelling and marked discomfort in the ear and ear drainage.
A disorder characterized by hypertrophy of the subcutaneous adipose tissue at the site of multiple subcutaneous injections of insulin.
A disorder characterized by subject-reported feeling of uncomfortable fullness of the abdomen.
A disorder characterized by a decrease in sexual desire.
A disorder characterized by an infectious process involving a stoma (surgically created opening on the surface of the body).
A disorder characterized by an infectious process involving the anal area and the rectum.
A disorder characterized by a sensation of marked discomfort on the lateral side of the body in the region below the ribs and above the hip.
A disorder characterized by a rupture in the wall of the esophagus.
A disorder characterized by bleeding from the duodenum.
A finding based on laboratory test results that indicate increased levels of cardiac troponin I in a biological specimen.
A disorder characterized by development of a malignancy most probably as a result of treatment for a previously existing malignancy.
Any monoclonal antibody that targets CD20.
Any agent that inhibits the activity of the enzyme CYP17A1.
Any substance or combination of substances that may be administered to human beings (or animals) for treating or preventing disease, or with the intent to make a medical diagnosis or to restore, correct or modify physiological functions. (IDMP)
The reemergence of anaplastic oligoastrocytoma after a period of remission.
The reemergence of anaplastic oligodendroglioma after a period of remission.
A response indicating that an individual's activity is normal with no limitations.
A response indicating that an individual is able to do little activity and spends most of the day in bed or chair.
A disorder characterized by swelling due to excessive fluid accumulation at a specific anatomic site.
A disorder characterized by leukemia arising as a result of the mutagenic effect of chemotherapy agents.
A disorder characterized by dizziness, imbalance, nausea, and vision problems.
A disorder characterized by a suspected candidal infection involving an oral mucosal surface.
A disorder characterized by systematic and extensive loss of memory.
A disorder characterized by bleeding from the anal region.
A disorder characterized by ulceration or inflammation of the mucous membrane of the anus.
A disorder characterized by a necrotic process occurring in the anal region.
Any agent that inhibits the activity of the androgen receptor (AR).
A disorder characterized by a sensation of marked discomfort in the chest wall.
A disorder characterized by a sensation of cold that often marks a physiologic response to sweating after a fever.
A disorder characterized by inflammation involving the gallbladder. It may be associated with the presence of gallstones.
A finding based on laboratory test results that indicate higher than normal levels of cholesterol in a blood specimen.
A disorder characterized by gradual and usually permanent loss of kidney function resulting in renal failure.
A disorder characterized by a deterioration in the ability to concentrate.
A finding based on laboratory test results that indicate an decrease in levels of corticotrophin in a blood specimen.
A disorder characterized by a sensation of marked discomfort in various parts of the head, not confined to the area of distribution of any nerve.
A disorder characterized by generalized inflammatory erythema and exfoliation. The inflammatory process involves > 90% of the body surface area.
A disorder characterized by failure of the left ventricle to produce adequate output.
A disorder characterized by reflux of the gastric and/or duodenal contents into the distal esophagus. It is chronic in nature and usually caused by incompetence of the lower esophageal sphincter, and may result in injury to the esophageal mucosal. Symptoms include heartburn and acid indigestion.
A disorder characterized by an inability to properly metabolize glucose.
A disorder characterized by diffuse reactive astrocytosis with multiple areas of necrotic foci without inflammation.
A disorder characterized by disturbances of milk secretion. It is not necessarily related to pregnancy that is observed in females and can be observed in males.
A finding based on laboratory test results that indicate higher than normal levels of the enzyme gamma-glutamyltransferase in the blood specimen. GGT (gamma-glutamyltransferase ) catalyzes the transfer of a gamma glutamyl group from a gamma glutamyl peptide to another peptide, amino acids or water.
A disorder characterized by a viral pathologic process involving the liver parenchyma.
A disorder characterized by dysfunction of the oculomotor nerve (third cranial nerve).
A situation referring to a severe reaction, risk or indication against use of a treatment or device.
A finding based on laboratory test results that indicate an decrease in levels of fibrinogen in a blood specimen.
A finding of damage to the musculoskeletal system during a surgical procedure.
A disorder characterized by inflammation of the salivary duct.
A disorder characterized by an infectious process involving the salivary gland.
A finding of leakage due to breakdown of a spermatic cord anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by functional disturbances of sensory neurons resulting in abnormal cutaneous sensations of tingling, numbness, pressure, cold, and/or warmth.
A disorder characterized by an area of epithelial tissue loss on the surface of the cornea. It is associated with inflammatory cells in the cornea and anterior chamber.
A finding of damage to the kidney during a surgical procedure.
A finding of leakage due to breakdown of a uterine anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by an infectious process involving the prostate gland.
A disorder characterized by compression of the urethra secondary to enlargement of the prostate gland. This results in voiding difficulties (straining to void, slow urine stream, and incomplete emptying of the bladder).
Stage II includes: T2, N0, M0. T2: Ovarian cancer with tumor involving one or both ovaries with pelvic extension below pelvic brim. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: IIA: (T1b, N0, M0); (T2, N0, M0); IIB: (T3, N0, M0). T1b: Penile cancer with tumor exhibiting lymphovascular invasion and/or perineural invasion or is high grade (i.e., grade 3 or sarcomatoid). T2: Penile cancer with tumor invading into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. T3: Penile cancer with tumor invading into corpora cavernosum (including tunica albuginea) with or without urethral invasion. N0: No lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: (cT1a-c, cT2a, N0, M0, PSA equal or more than 10 and less than 20, Grade Group 1); (cT2b-c, N0, M0, PSA less than 20, Grade Group 1); IIB: T1-2, N0, M0, PSA less than 20, Grade Group 2; IIC: (T1-2, N0, M0, PSA less than 20, Grade Group 3); (T1-2, N0, M0, PSA less than 20, Grade Group 4). cT1a: Prostate cancer in which the tumor is an incidental histologic finding in 5% or less of tissue resected. cT1b: Prostate cancer in which the tumor is an incidental histologic finding in more than 5% of tissue resected. cT1c: Prostate cancer in which the tumor is identified by needle biopsy found in one or both sides, but not palpable. cT2a: Prostate cancer in which the tumor involves one-half of one side or less. cT2b: Prostate cancer in which the tumor involves more than one-half of one side but not both sides. cT2c: Prostate cancer in which the tumor involves both sides. T1: Prostate cancer with clinically inapparent tumor that is not palpable. T2: Prostate cancer in which the tumor is palpable and confined within the prostate. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 1: Gleason Score 6 or less, Gleason Pattern 3 or less+3. Grade Group 2: Gleason Score 7, Gleason Pattern 3+4. Grade Group 3: Gleason Score 7, Gleason Pattern 4+3. Grade Group 4: Gleason Score 8, Gleason Pattern 4+4. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Tumor measuring more than 7 cm in greatest dimension, limited to the kidney. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Tumor invades the muscularis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: (T2, N0, M0); (T3, N0, M0). T2: Tumor measuring more than 2 cm but less than 4 cm in greatest dimension limited to the thyroid. T3: Tumor measuring 4 cm or more in greatest dimension or with extrathyroidal extension. N0: No evidence of locoregional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: For male penile urethra and female urethra: Tumor invades any of the following: corpus spongiosum, periurethral muscle. For prostatic urethra: Tumor invades the prostatic stroma surrounding ducts either by direct extension from the urothelial surface or by invasion from prostatic ducts. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: T2, N0, M0. T2: Uterine corpus carcinoma or carcinosarcoma with tumor invading the stromal connective tissue of the cervix but not extending beyond the uterus. Does not include endocervical glandular involvement. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: IIA: T2a, N0, M0; IIB: T2b, N0, M0. T2a: Tumor invading paravaginal tissues but not to pelvic wall, measuring 2.0 cm or less. T2b: Tumor invading paravaginal tissues but not to pelvic wall, measuring more than 2.0 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIA includes: T2a, Any N, M0. T2a: Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina without parametrial invasion. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIA includes: T2a, N0, M0. T2a: Fallopian tube cancer with extension and/or implants on the uterus and/or fallopian tube(s) and/or ovaries. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIA includes: T2a, N0, M0. T2a: Ovarian cancer with tumor extension and/or implants on the uterus and/or fallopian tube(s) and/or ovaries. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIA includes: (cT1a-c, cT2a, N0, M0, PSA equal or more than 10 and less than 20, Grade Group 1); (cT2b-c, N0, M0, PSA less than 20, Grade Group 1). cT1a: Prostate cancer in which the tumor is an incidental histologic finding in 5% or less of tissue resected. cT1b: Prostate cancer in which the tumor is an incidental histologic finding in more than 5% of tissue resected. cT1c: Prostate cancer in which the tumor is identified by needle biopsy found in one or both sides, but not palpable. cT2a: Prostate cancer in which the tumor involves one-half of one side or less. cT2b: Prostate cancer in which the tumor involves more than one-half of one side but not both sides. cT2c: Prostate cancer in which the tumor involves both sides. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 1: Gleason Score 6 or less, Gleason Pattern 3 or less+3. (AJCC 8th ed.)
A reduction in voltage of the PR segment below baseline. []
A disorder characterized by dysfunction of the trigeminal nerve (fifth cranial nerve).
A disorder characterized by dysfunction of the accessory nerve (eleventh cranial nerve).
A disorder characterized by blockage of the uterine outlet.
A disorder characterized by greater than 30% total body skin area separation of dermis. The syndrome is thought to be a hypersensitivity complex affecting the skin and the mucous membranes.
A finding of separation of the approximated margins of a surgical wound.
A disorder characterized by inflammation, swelling and redness to the conjunctiva of the eye.
A disorder characterized by an inability to achieve orgasm.
A finding of development of a new problem at the site of an existing wound.
A disorder characterized by inflammation of the throat.
A disorder characterized by a narrowing of the laryngeal airway.
A disorder characterized by a decrease in production of thyroid hormone by the thyroid gland.
A disorder characterized by swelling of the abdomen.
A finding of damage to the hepatic parenchyma and/or biliary tract during a surgical procedure.
A disorder characterized by swelling due to an excessive accumulation of fluid around the orbits of the face.
A disorder characterized by a false sensory perception in the absence of an external stimulus.
A disorder characterized by an infectious process involving the gums.
A finding of leakage due to breakdown of a urethral anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the stomach.
A finding indicating that there is a decrease based on a predetermined threshold in the size and the extent of tissue involvement by cancer following an initial apparent radiographic progression.
The disappearance of all signs of cancer following an initial apparent radiographic progression.
A disorder characterized by a conspicuous change in cognitive function.
A disorder characterized by an abnormal communication between the large intestine and another organ or anatomic site.
A disorder characterized by bleeding from the colon.
A disorder characterized by blockage of the normal flow of the intestinal contents in the colon.
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the colon.
A disorder characterized by an infectious process involving the lips.
A disorder characterized by bleeding from the lower gastrointestinal tract (small intestine, large intestine, and anus).
A disorder characterized by a sensation of marked discomfort in the skin covering the top and the back of the head.
A disorder characterized by involvement of the sclera of the eye.
A response indicating that an individual is not their normal self, but able to be up and about with fairly normal activity.
A response indicating that an individual is not feeling up to most things, but in bed or chair less than half the day.
A disorder characterized by a sensation of marked discomfort in the scrotal area.
A disorder characterized by a sudden, involuntary skeletal muscular contractions of cerebral or brain stem origin.
A finding based on laboratory test results that indicate an increase in the levels of amylase in a serum specimen.
A disorder characterized by a delayed-type hypersensitivity reaction to foreign proteins derived from an animal serum. It occurs approximately six to twenty-one days following the administration of the foreign antigen. Symptoms include fever, arthralgias, myalgias, skin eruptions, lymphadenopathy, chest marked discomfort and dyspnea.
A disorder characterized by accumulation of fluid in the lung tissues that causes a disturbance of the gas exchange that may lead to respiratory failure.
A disorder characterized by the replacement of the lung tissue by connective tissue, leading to progressive dyspnea, respiratory failure or right heart failure.
A disorder characterized by an abnormal communication between the lung and another organ or anatomic site.
A disorder characterized by a defect in pulmonary valve function or structure.
Stage IIA1 includes: T2a1, Any N, M0. T2a1: Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina without parametrial invasion. Clinically visible lesion 4.0 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIA2 includes: T2a2, Any N, M0. T2a2: Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina without parametrial invasion. Clinically visible lesion more than 4.0 cm in greatest dimension. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIB includes: T2b, Any N, M0. T2b: Cervical carcinoma invading beyond the uterus but not to the pelvic wall or to lower third of vagina with parametrial invasion. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIB includes: T2b, N0, M0. T2b: Fallopian tube cancer with tumor extension to and/or implants on other pelvic tissues. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIB includes: T2b, N0, M0. T2b: Ovarian cancer with tumor extension to and/or implants on other pelvic tissues. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIB includes: T1-2, N0, M0, PSA less than 20, Grade Group 2. T1: Prostate cancer with clinically inapparent tumor that is not palpable. T2: Prostate cancer in which the tumor is palpable and confined within the prostate. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 2: Gleason Score 7, Gleason Pattern 3+4. (AJCC 8th ed.)
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, Any N, M0); (T4, Any N, M0). T1: Tumor measuring 5 cm or less in greatest dimension, with no extra-adrenal invasion. T2: Tumor measuring more than 5 cm in greatest dimension, with no extra-adrenal invasion. T3: Tumor of any size with local invasion but not invading adjacent organs. T4: Tumor of any size that invades adjacent organs (kidney, diaphragm, pancreas, spleen, or liver) or large blood vessels (renal vein or vena cava). N1: Metastasis in regional lymph node(s). M0: No distant metastasis. (from AJCC 8th Ed.)
Stage III includes: IIIA: (T3a, T3b, T4a, N0, M0); (T1-T4a, N1, M0); IIIB: (T1-T4a, N2, N3, M0). T1: Tumor invades lamina propria (subepithelial connective tissue). T2: Tumor invades muscularis propria. T3: Tumor invades perivesical soft tissue. T3a: Tumor invades perivesical soft tissue, microscopically. T3b: Tumor invades perivesical soft tissue, macroscopically (extravesical mass). T4a: Extravesical tumor invades directly into prostatic stroma, uterus, vagina. N0: No regional lymph node metastasis. N1: Single regional lymph node metastasis in the true pelvis (perivesical, obturator, internal and external iliac, or sacral lymph node). N2: Multiple regional lymph node metastasis in the true pelvis (perivesical, obturator, internal and external iliac, or sacral lymph node metastasis). N3: Lymph node metastasis to the common iliac lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: T3, Any N, M0. T3: Tumor extending to pelvic sidewall and/or involving the lower third of vagina, and/or causing hydronephrosis or nonfunctioning kidney. M0: No distant metastasis. (AJCC 8th Ed.)
A disorder characterized by painful or difficult coitus.
Cancer that is neither decreasing nor increasing in extent or severity based on predetermined boundaries following an initial apparent radiographic progression.
A response indicating that an individual is unable to swallow.
The extent to which a diagnostic or therapeutic product achieves its intended effect in the typical clinical setting.
A disorder characterized by the inability to speak. It may result from injuries to the vocal cords or may be functional (psychogenic).
A disorder characterized by acute inflammation to the vermiform appendix caused by a pathogenic agent.
A disorder characterized by inflammation of the arachnoid membrane and adjacent subarachnoid space.
A disorder characterized by an infectious process involving the conjunctiva. Clinical manifestations include pink or red color in the eyes.
A disorder characterized by an infectious process involving the cornea.
A finding based on laboratory test results that indicate an increase in levels of creatine phosphokinase in a blood specimen.
A disorder characterized by an infectious process involving a cranial nerve.
A finding based on laboratory test results that indicate increased levels of creatinine in a biological specimen.
A disorder characterized by an infectious process involving the lymph nodes.
A disorder characterized by a sensation of marked discomfort in a lymph node.
A disorder characterized by excessive fluid collection in tissues that causes swelling.
A finding based on laboratory test results that indicate an abnormal increase in the number of lymphocytes in the blood, effusions or bone marrow.
A disorder characterized by the reactivation of herpes zoster virus.
A disorder characterized by involvement of the paranasal sinuses.
A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates in the sinus node.
A disorder characterized by an infectious process involving the mucous membranes of the paranasal sinuses.
A disorder characterized by the degeneration and thinning of the epidermis and dermis.
A disorder characterized by darkening of the skin due to excessive melanin deposition.
A disorder characterized by loss of skin pigment (e.g., vitiligo).
A disorder characterized by an area of hardness in the skin.
A disorder characterized by the presence of one or more warts.
A finding of acute skin inflammatory reaction caused by drugs, especially chemotherapeutic agents, for weeks or months following radiotherapy. The inflammatory reaction is confined to the previously irradiated skin and the symptoms disappear after the removal of the pharmaceutical agent.
A disorder characterized by inflammation involving a nerve root. Patients experience marked discomfort radiating along a nerve path because of spinal pressure on the connecting nerve root.
A finding of leakage due to breakdown of a rectal anastomosis (surgical connection of two separate anatomic structures).
Stage III includes: 55 years and older: T4a, Any N, M0. T4a: Gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve from a tumor of any size. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage III includes: IIIA1: T1/2, N1, M0; IIIA2: T3a, N0/N1, M0; IIIB: T3b, N0/N1, M0; IIIC: T3c, N0/N1, M0. T1: Fallopian tube cancer with tumor limited to fallopian tube(s). T2: Fallopian tube cancer with tumor involving fallopian tubes with pelvic extension below pelvic brim. T3a: Fallopian tube cancer with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. T3b: Fallopian tube cancer with macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension with or without metastasis to the retroperitoneal lymph nodes. T3c: Fallopian tube cancer with macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ). N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: IIIA1: T1/2, N1, M0; IIIA2: T3a, N0/N1, M0; IIIB: T3b, N0/N1, M0; IIIC: T3c, N0/N1, M0. T1: Ovarian cancer with tumor limited to ovaries (one or both). T2: Ovarian cancer with tumor involving one or both ovaries with pelvic extension below pelvic brim. T3a: Ovarian cancer with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. T3b: Ovarian cancer with macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension with or without metastasis to the retroperitoneal lymph nodes. T3c: Ovarian cancer with macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ). N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: IIIA: T1-3, N1, M0; IIIB: T1-3, N2, M0. T1: Glans: Penile cancer with tumor invading lamina propria. Foreskin: Penile cancer with tumor invading dermis, lamina propria, or dartos fascia. Shaft: Penile cancer with tumor invading connective tissue between epidermis and corpora regardless of location. All sites with or without lymphovascular invasion or perineural invasion and is or is not high grade. T2: Penile cancer with tumor invading into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. T3: Penile cancer with tumor invading into corpora cavernosum (including tunica albuginea) with or without urethral invasion. N1: Penile cancer with two or less unilateral inguinal metastases, no extranodal extension. N2: Penile cancer with three or more unilateral inguinal metastases or bilateral metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: T3a, N0/N1, M0; IIIB: T3b, N0/N1, M0; IIIC: T3c, N0/N1, M0. T3a: Primary peritoneal cancer with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. T3b: Primary peritoneal cancer with macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension with or without metastasis to the retroperitoneal lymph nodes. T3c: Primary peritoneal cancer with macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ). N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: IIIA: T1-2, N0, M0, PSA 20 or more, Grade Group 1-4; IIIB: T3-4, N0, M0, PSA: Any, Grade Group 1-4; IIIC: Any T, N0, M0, PSA: Any, Grade Group 5. T1: Prostate cancer with clinically inapparent tumor that is not palpable. T2: Prostate cancer in which the tumor is palpable and confined within the prostate. T3: Prostate cancer with extraprostatic tumor that is not fixed or does not invade adjacent structures. T4: Prostate cancer in which the tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 1: Gleason Score 6 or less, Gleason Pattern 3 or less+3. Grade Group 2: Gleason Score 7, Gleason Pattern 3+4. Grade Group 3: Gleason Score 7, Gleason Pattern 4+3. Grade Group 4: Gleason Score 8, Gleason Pattern 4+4. Grade Group 5: Gleason Score 9 or 10, Gleason Pattern 4+5, or 5+4, or 5+5. (AJCC 8th ed.)
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, N0, M0); (T3, N1, M0). T1: Tumor measuring 7 cm or less in greatest dimension, limited to the kidney. T2: Tumor measuring more than 7 cm in greatest dimension, limited to the kidney. T3: Tumor extending into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota's fascia. N0: No regional lymph node metastasis. N1: Metastasis in regional lymph node(s). M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: T3, N0, M0. T3: For renal pelvis only: Tumor invades beyond muscularis into peripelvic fat or into the renal parenchyma. For ureter only: Tumor invades beyond muscularis into periureteric fat. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: T3, N0, M0. T3: Tumor invades beyond muscularis into peripelvic fat or into the renal parenchyma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: T1-3, N1a, M0. T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but less than 4 cm in greatest dimension limited to the thyroid. T3: Tumor measuring 4 cm or more in greatest dimension or with extrathyroidal extension. N1a: Metastasis to level VI or VII (pretracheal, paratracheal, or prelaryngeal/Delphian, or upper mediastinal) lymph nodes. This can be unilateral or bilateral disease. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage III includes: T3, N0, M0. T3: Tumor invades beyond muscularis into periureteric fat. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, N0, M0); (T3, N1, M0). T1: For male penile urethra and female urethra: Tumor invades subepithelial connective tissue. For prostatic urethra: Tumor invades urethral subepithelial connective tissue immediately underlying the urothelium. T2: For male penile urethra and female urethra: Tumor invades any of the following: corpus spongiosum, periurethral muscle. For prostatic urethra: Tumor invades the prostatic stroma surrounding ducts either by direct extension from the urothelial surface or by invasion from prostatic ducts. T3: For male penile urethra and female urethra: Tumor invades any of the following: corpus cavernosum, anterior vagina. For prostatic urethra: Tumor invades the periprostatic fat. N0: No regional lymph node metastasis. N1: Single regional lymph node metastasis in the inguinal region or true pelvis [perivesical, obturator, internal (hypogastric) and external iliac], or presacral lymph node. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: T3, N0, M0. T3: Uterine corpus carcinoma or carcinosarcoma with tumor involving serosa, adnexa, vagina, or parametrium. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: (T1-T3, N1, M0); (T3, N0, M0). T1: Tumor confined to the vagina. T2: Tumor invading paravaginal tissues but not to pelvic sidewall. T3: Tumor extending to the pelvic sidewall and/or involving the lower third of the vagina and/or causing hydronephrosis or nonfunctioning kidney. N0: No regional lymph node metastasis. N1: Pelvic or inguinal lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA includes: T3a, Any N, M0. T3a: Tumor involving the lower third of vagina but not extending to pelvic wall. M0: No distant metastasis. (AJCC 8th Ed.)
A disorder characterized by an exaggerated feeling of well-being which is disproportionate to events and stimuli.
A disorder characterized by laboratory test results that indicate an elevation in the concentration of triglyceride concentration in the blood.
Stage IV includes: IVA: T4, Any N, M0; IVB: Any T, Any N, M1. T4: Tumor invading the mucosa of the bladder or rectum and/or extending beyond the true pelvis (bullous edema is not sufficient evidence to classify a tumor as T4). M0: No distant metastasis. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage IVA includes: T4, Any N, M0. T4: Tumor invading the mucosa of the bladder or rectum and/or extending beyond the true pelvis (bullous edema is not sufficient evidence to classify a tumor as T4). M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage I includes: T1, Any N, M0. T1: Tumor confined to uterus (extension to corpus should be disregarded). M0: No distant metastasis. (AJCC 8th Ed.)
The subject, who met eligibility criteria, was not assigned to an arm and was not treated.
A disorder characterized by an infectious process involving an artery.
A disorder characterized by accumulation of serous or hemorrhagic fluid in the peritoneal cavity.
A disorder characterized by a dysrhythmia without cardiac electrical activity. Typically, this is accompanied by cessation of the pumping function of the heart.
A disorder characterized by a dysrhythmia with a delay in the time required for the conduction of an electrical impulse through the atrioventricular (AV) node beyond 0.2 seconds; prolongation of the PR interval greater than 200 milliseconds.
A disorder characterized by signs and symptoms that resemble Cushing's disease or syndrome: buffalo hump obesity, striations, adiposity, hypertension, diabetes, and osteoporosis, usually due to exogenous corticosteroids.
A disorder characterized by a bluish discoloration of the skin and/or mucous membranes.
A change in the amino acid residue at position 148 in the cyclin-dependent kinase inhibitor 2 protein where alanine has been replaced by threonine.
A change in the amino acid residue at position 147 in the cyclin-dependent kinase inhibitor 2 protein where alanine has been replaced by threonine.
A disorder characterized by ulceration or inflammation of the mucous membrane of the small intestine.
A disorder characterized by blockage of the normal flow of the intestinal contents of the small intestine.
A disorder characterized by a rupture in the small intestine wall.
A disorder characterized by an infectious process involving the small intestine.
A disorder characterized by a narrowing of the lumen of the rectum.
A disorder characterized by the involuntary expulsion of air from the nose.
A disorder characterized by a sensation of marked discomfort in the esophageal region.
A disorder characterized by laboratory test results that indicate a low concentration of glucose in the blood.
A disorder characterized by an inability to see clearly in dim light.
A disorder characterized by an infectious process involving soft tissues.
A disorder characterized by the presence of blood in a fallopian tube.
A disorder characterized by a sensation of marked discomfort in the rectal region.
A disorder characterized by a rupture in the rectal wall.
Stage IIIB includes: T3b, Any N, M0. T3b: extending to pelvic wall and/or causing hydronephrosis or nonfunctioning kidney. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIB includes: T3b, N0/N1, M0. T3b: Fallopian tube cancer with macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension with or without metastasis to the retroperitoneal lymph nodes. N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIB includes: T3b, N0/N1, M0. T3b: Ovarian cancer with macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension with or without metastasis to the retroperitoneal lymph nodes. N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIB includes: T1-3, N2, M0. T1: Glans: Penile cancer with tumor invading lamina propria. Foreskin: Penile cancer with tumor invading dermis, lamina propria, or dartos fascia. Shaft: Penile cancer with tumor invading connective tissue between epidermis and corpora regardless of location. All sites with or without lymphovascular invasion or perineural invasion and is or is not high grade. T2: Penile cancer with tumor invading into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. T3: Penile cancer with tumor invading into corpora cavernosum (including tunica albuginea) with or without urethral invasion. N2: Penile cancer with three or more unilateral inguinal metastases or bilateral metastases. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: T3b, N0/N1, M0. T3b: Primary peritoneal cancer with macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension with or without metastasis to the retroperitoneal lymph nodes. N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Uterine corpus carcinoma or carcinosarcoma with vaginal involvement (direct extension or metastasis) or parametrial involvement. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IIIA includes: IIIA1: T1/2, N1, M0; IIIA2: T3a, N0/N1, M0. T1: Fallopian tube cancer with tumor limited to fallopian tube(s). T2: Fallopian tube cancer with tumor involving fallopian tubes with pelvic extension below pelvic brim. T3a: Fallopian tube cancer with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA includes: IIIA1: T1/2, N1, M0; IIIA2: T3a, N0/N1, M0. T1: Ovarian cancer with tumor limited to ovaries (one or both). T2: Ovarian cancer with tumor involving one or both ovaries with pelvic extension below pelvic brim. T3a: Ovarian cancer with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA includes: T1-3, N1, M0. T1: Glans: Penile cancer with tumor invading lamina propria. Foreskin: Penile cancer with tumor invading dermis, lamina propria, or dartos fascia. Shaft: Penile cancer with tumor invading connective tissue between epidermis and corpora regardless of location. All sites with or without lymphovascular invasion or perineural invasion and is or is not high grade. T2: Penile cancer with tumor invading into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. T3: Penile cancer with tumor invading into corpora cavernosum (including tunica albuginea) with or without urethral invasion. N1: Penile cancer with two or less unilateral inguinal metastases, no extranodal extension. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: T3a, N0/N1, M0. T3a: Primary peritoneal cancer with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA includes: T3a, N0, M0. T3a: Uterine corpus carcinoma or carcinosarcoma with tumor involving the serosa and/or adnexa (direct extension or metastasis). N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
A disorder characterized by a sensation of marked discomfort in the uterus.
A disorder characterized by a rupture in the uterine wall.
A finding of leakage due to breakdown of a vaginal anastomosis (surgical connection of two separate anatomic structures).
Vaginal cancer with tumor confined to the vagina, measuring more than 2.0 cm. (from AJCC 8th Ed.)
Vaginal cancer with tumor confined to the vagina. (from AJCC 8th Ed.)
Vaginal cancer with tumor confined to the vagina, measuring 2.0 cm or less. (from AJCC 8th Ed.)
Vaginal cancer with tumor invading paravaginal tissues but not to pelvic sidewall. (from AJCC 8th Ed.)
Vaginal cancer with tumor invading paravaginal tissues but not to pelvic wall, measuring more than 2.0 cm. (from AJCC 8th Ed.)
Vaginal cancer with tumor invading paravaginal tissues but not to pelvic wall, measuring 2.0 cm or less. (from AJCC 8th Ed.)
Vaginal cancer with pelvic or inguinal lymph node metastasis. (from AJCC 8th Ed.)
Vaginal cancer with tumor extending to the pelvic sidewall and/or involving the lower third of the vagina and/or causing hydronephrosis or nonfunctioning kidney. Pelvic sidewall is defined as the muscle, fascia, neurovascular structures, or skeletal portions of the bony pelvis. (from AJCC 8th Ed.)
Stage IV includes: IVA: T4, Any N, M0; IVB: Any T, Any N, M1. T4: Tumor invading the mucosa of the bladder or rectum, and/or extending beyond the true pelvis (bullous edema is not sufficient to classify a tumor as T4). M0: No distant metastasis. M1: Distant metastasis (including peritoneal spread or involvement of the supraclavicular, mediastinal, or distant lymph nodes; lung; liver; or bone). (from AJCC 8th Ed.)
Stage IVA includes: T4, Any N, M0. T4: Tumor invading the mucosa of the bladder or rectum, and/or extending beyond the true pelvis (bullous edema is not sufficient to classify a tumor as T4). M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis (including peritoneal spread or involvement of the supraclavicular, mediastinal, or distant lymph nodes; lung; liver; or bone). (from AJCC 8th Ed.)
Stage IIIC includes: IIIC1: T1-T3, N1/N1mi/N1a, M0; IIIC2: T1-T3, N2/N2mi/N2a, M0. T1: Uterine corpus carcinoma or carcinosarcoma with tumor confined to the corpus uteri, including endocervical glandular involvement. T2: Uterine corpus carcinoma or carcinosarcoma with tumor invading the stromal connective tissue of the cervix but not extending beyond the uterus. Does not include endocervical glandular involvement. T3: Uterine corpus carcinoma or carcinosarcoma with tumor involving serosa, adnexa, vagina, or parametrium. N1: Regional lymph node metastasis to pelvic lymph nodes. N1mi: Regional lymph node metastasis (greater than 0.2 mm but nor greater than 2.0 mm in diameter) to pelvic lymph nodes. N1a: Regional lymph node metastasis (greater than 2.0 mm in diameter) to pelvic lymph nodes. N2: Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. N2mi: Regional lymph node metastasis (greater than 0.2 mm but not greater than 2.0 mm in diameter) to para-aortic lymph nodes, with or without positive pelvic lymph nodes. N2a: Regional lymph node metastasis (greater than 2.0 mm in diameter) to para-aortic lymph nodes, with or without positive pelvic lymph nodes. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IIIC1 includes: T1-T3, N1/N1mi/N1a, M0. T1: Uterine corpus carcinoma or carcinosarcoma with tumor confined to the corpus uteri, including endocervical glandular involvement. T2: Uterine corpus carcinoma or carcinosarcoma with tumor invading the stromal connective tissue of the cervix but not extending beyond the uterus. Does not include endocervical glandular involvement. T3: Uterine corpus carcinoma or carcinosarcoma with tumor involving serosa, adnexa, vagina, or parametrium. N1: Regional lymph node metastasis to pelvic lymph nodes. N1mi: Regional lymph node metastasis (greater than 0.2 mm but nor greater than 2.0 mm in diameter) to pelvic lymph nodes. N1a: Regional lymph node metastasis (greater than 2.0 mm in diameter) to pelvic lymph nodes. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IIIC2 includes: T1-T3, N2/N2mi/N2a, M0. T1: Uterine corpus carcinoma or carcinosarcoma with tumor confined to the corpus uteri, including endocervical glandular involvement. T2: Uterine corpus carcinoma or carcinosarcoma with tumor invading the stromal connective tissue of the cervix but not extending beyond the uterus. Does not include endocervical glandular involvement. T3: Uterine corpus carcinoma or carcinosarcoma with tumor involving serosa, adnexa, vagina, or parametrium. N2: Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. N2mi: Regional lymph node metastasis (greater than 0.2 mm but not greater than 2.0 mm in diameter) to para-aortic lymph nodes, with or without positive pelvic lymph nodes. N2a: Regional lymph node metastasis (greater than 2.0 mm in diameter) to para-aortic lymph nodes, with or without positive pelvic lymph nodes. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IV includes: IVA: T4, Any N, M0; IVB: Any T, Any N, M1. T4: Uterine corpus carcinoma or carcinosarcoma with tumor invading the bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4). M0: No distant metastasis. M1: Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, lung, liver, or bone. It excludes metastasis to pelvic or para-aortic lymph nodes, vagina, uterine serosa, or adnexa). (from AJCC 8th Ed.)
Stage IVA includes: T4, Any N, M0. T4: Uterine corpus carcinoma or carcinosarcoma with tumor invading the bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4). M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVB includes: Any T, Any N, M1. M1: Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, lung, liver, or bone. It excludes metastasis to pelvic or para-aortic lymph nodes, vagina, uterine serosa, or adnexa). (from AJCC 8th Ed.)
Stage IIIC includes: T3c, N0/N1, M0. T3c: Ovarian cancer with macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ). N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IV includes: Any T, Any N, M1: M1: Distant metastasis, including pleural effusion with positive cytology; liver or splenic parenchymal metastasis; metastasis to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside the abdominal cavity); and transmural involvement of intestine. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Fallopian tube cancer with tumor limited to fallopian tube(s). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
A disorder characterized by loss of function or tissue destruction of an organ or multiple organs, arising from humoral or cellular immune responses of the individual to his own tissue constituents.
A disorder characterized by abnormal, repetitive, involuntary muscle movements, frenzied speech and extreme restlessness.
A disorder characterized by an infectious process involving the eye.
A disorder characterized by a sensation of marked discomfort in the eye.
A disorder characterized by a reduction in the strength of the facial muscles.
A disorder characterized by dysfunction of the facial nerve (seventh cranial nerve).
A finding of sudden movement downward, usually resulting in injury.
A finding of leakage due to breakdown of a fallopian tube anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by blockage of the normal flow of the contents in the fallopian tube.
A disorder characterized by a rupture of the fallopian tube wall.
A disorder characterized by inflammation of the bladder which is not caused by an infection of the urinary tract.
A disorder characterized by sexual dysfunction characterized by a delay in climax.
A disorder characterized by neck stiffness, headache, and photophobia resulting from irritation of the cerebral meninges.
A disorder characterized by abnormally heavy vaginal bleeding during menses.
A disorder characterized by a necrotic process occurring in the soft tissues of the upper extremity.
A disorder characterized by characterized by excessive sleepiness and drowsiness.
A disorder characterized by increased involuntary muscle tone that affects the regions interfering with voluntary movement. It results in gait, movement, and speech disturbances.
A disorder characterized by blockage of the normal flow of the contents of the spermatic cord.
Stage IIIC includes: T3c, N0/N1, M0. T3c: Fallopian tube cancer with macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ). N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIC includes: T3c, N0/N1, M0. T3c: Primary peritoneal cancer with macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ). N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IV includes: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage IV includes: IVA: (T4b, N0, M0); (Any T, Any N, M1a); IVB: (Any T, Any N, M1b). T4b: Extravesical tumor invades pelvic wall, abdominal wall. N0: No regional lymph node metastasis. M0: No distant metastasis. M1a: Distant metastasis limited to lymph nodes beyond the common iliacs. M1b: Non-lymph node distant metastases. (AJCC 8th ed.)
Stage IV includes: (T4, Any N, M0); (Any T, N3, M0); (Any T, Any N, M1). T4: Penile cancer with tumor invading into adjacent structures (i.e., scrotum, prostate, pubic bone). N3: Penile cancer with extranodal extension of lymph node metastases or pelvic lymph node metastases. M1: Distant metastasis present. (AJCC 8th ed.)
Stage IV includes: IVA: Any T, N1, M0, PSA: Any, Grade Group: Any; IVB: Any T, N0, M1, PSA: Any, Grade Group: Any. N0: Prostate cancer with no positive regional nodes. N1: Prostate cancer with metastases in regional node(s). M0: Prostate cancer without evidence of distant metastasis. M1: Prostate cancer with distant metastasis. (AJCC 8th ed.)
Stage IV includes: (T4, Any N, M0); (Any T, Any N, M1). T4: Tumor invading beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland). M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
A disorder characterized by an uncomfortable feeling of itching and burning in the vagina.
A disorder characterized by an infectious process involving the vagina.
A disorder characterized by blockage of vaginal canal.
A disorder characterized by a sensation of marked discomfort in the vagina.
A disorder characterized by a rupture in the vaginal wall.
A disorder characterized by a narrowing of the vaginal canal.
A finding of leakage due to breakdown of a vas deferens anastomosis (surgical connection of two separate anatomic structures).
A finding of a previously undocumented problem related to the vascular access site.
A disorder characterized by a sudden drop of the blood pressure, bradycardia, and peripheral vasodilation that may lead to loss of consciousness. It results from an increase in the stimulation of the vagus nerve.
A disorder characterized by a dysrhythmia that originates in the ventricles.
A disorder characterized by a deterioration in memory function.
A disorder characterized by a queasy sensation and/or the urge to vomit.
Stage 0 includes: 0is: Tis, N0, M0; 0a: Ta, N0, M0. Tis: Penile cancer with a finding of carcinoma in situ (penile intraepithelial neoplasia [PeIN]). Ta: Penile cancer with a finding of noninvasive localized squamous cell carcinoma. N0: No lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0a includes: Ta, N0, M0. Ta: Papillary noninvasive carcinoma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0is includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: (T4, N0, M0); (Any T, N1, M0); (Any T, N2, M0); (Any T, Any N, M1). T4: Tumor invades adjacent organs, or through the kidney into the perinephric fat. N0: No regional lymph node metastasis. N1: Metastasis in a single lymph node, 2 cm or less in greatest dimension. N2: Metastasis in a single lymph node, more than 2 cm in greatest dimension; or multiple lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage 0a includes: Ta, N0, M0. Ta: Non-invasive papillary carcinoma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0is includes: Tis, N0, M0. Tis: Urothelial carcinoma in situ: ""flat tumor"". N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
A disorder characterized by an ANC <1000/mm3 and a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >=38 degrees C (100.4 degrees F) for more than one hour
A disorder characterized by inability to control the escape of stool from the rectum.
A disorder characterized by the development of secondary female sex characteristics in males due to extrinsic factors.
A disorder characterized by false personal beliefs held contrary to reality, despite contradictory evidence and common sense.
A disorder characterized by the decay of a tooth, in which it becomes softened, discolored and/or porous.
A disorder characterized by a decrease in ability to perceive and respond.
A disorder characterized by an infectious process involving the use of a medical device.
A disorder characterized by a disturbing sensation of lightheadedness, unsteadiness, giddiness, spinning or rocking.
A disorder characterized by inflammation (physiologic response to irritation), swelling and redness to the middle ear.
A disorder characterized by a defect in mitral valve function or structure.
A disorder characterized by harsh and raspy voice arising from or spreading to the larynx.
A disorder characterized by pressure on the spinal cord.
A finding of traumatic injury to the spine in which the continuity of a vertebral bone is broken.
Stage IV includes: IVA: 55 years and older: T4b, Any N, M0; IVB: 55 years and older: Any T, Any N, M1. T4b: Gross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels from a tumor of any size. M0: No distant metastasis. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage IV includes: IVA: (T4a, Any N, M0); (T1-3, N1b, M0); IVB: (T4b, Any N, M0); IVC: (Any T, Any N, M1). T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but less than 4 cm in greatest dimension limited to the thyroid. T3: Tumor measuring 4 cm or more in greatest dimension or with extrathyroidal extension. T4a: Moderately advanced disease; tumor of any size with gross extrathyroidal extension into the nearby tissues of the neck, including subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve. T4b: Very advanced disease; tumor of any size with extension towards the spine or into nearby large blood vessels, invading the prevertebral fascia, or encasing the carotid artery or mediastinal vessels. N1b: Metastasis to unilateral, bilateral, or contralateral lateral neck lymph nodes levels I, II, III, IV, or V or retropharyngeal lymph nodes. M0: No distant metastasis. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage IV includes: (T4, N0, M0); (T4, N1, M0); (Any T, N2, M0); (Any T, Any N, M1). T4: For male penile urethra and female urethra: Tumor invades other adjacent organs (e.g., invasion of the bladder wall). For prostatic urethra: Tumor invades other adjacent organs (e.g., extraprostatic invasion of the bladder wall, rectal wall). N0: No regional lymph node metastasis. N1: Single regional lymph node metastasis in the inguinal region or true pelvis [perivesical, obturator, internal (hypogastric) and external iliac], or presacral lymph node. N2: Multiple regional lymph node metastasis in the inguinal region or true pelvis [perivesical, obturator, internal (hypogastric) and external iliac], or presacral lymph node. M0: No distant metastasis. M1: Distant metastasis. (AJCC 8th ed.)
Stage IVA includes: (T4b, N0, M0); (Any T, Any N, M1a). T4b: Extravesical tumor invades pelvic wall, abdominal wall. N0: No regional lymph node metastasis. M0: No distant metastasis. M1a: Distant metastasis limited to lymph nodes beyond the common iliacs. (AJCC 8th ed.)
A disorder characterized by metabolic abnormalities that result from a spontaneous or therapy-related cytolysis of tumor cells.
A disorder characterized by a sensation of marked discomfort from a neoplasm that may be pressing on a nerve, blocking blood vessels, inflamed or fractured from metastasis.
A disorder characterized by necrotizing enterocolitis in neutropenic patients.
A disorder characterized by a decrease in blood supply due to narrowing or blockage of a visceral (mesenteric) artery.
A disorder characterized by a decrease in visual acuity.
A disorder characterized by bleeding into the vitreous humor.
Stage I includes: T1, N0, M0. T1: Tumor invades lamina propria (subepithelial connective tissue). N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IVB includes: Any T, Any N, M1b. M1b: Non-lymph node distant metastases. (AJCC 8th ed.)
Stage 0a includes: Ta, N0, M0. Ta: For male penile urethra and female urethra: Non-invasive papillary carcinoma. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0is includes: Tis, N0, M0. Tis: For male penile urethra and female urethra: Carcinoma in situ. For prostatic urethra: Carcinoma in situ involving the prostatic urethra or periurethral or prostatic ducts without stromal invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IVA includes: 55 years and older: T4b, Any N, M0. T4b: Gross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels from a tumor of any size. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVB includes: 55 years and older: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage IVA includes: T1-T3a, N0/NX, M0. T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but 4 cm or less in greatest dimension limited to the thyroid. T3a: Tumor measuring more than 4 cm in greatest dimension limited to the thyroid. N0: No evidence of locoregional lymph node metastasis. NX: Regional lymph nodes cannot be assessed. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVB includes: (T1-T3a, N1, M0); (T3b, Any N, M0); (T4, Any N, M0). T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but 4 cm or less in greatest dimension limited to the thyroid. T3a: Tumor measuring more than 4 cm in greatest dimension limited to the thyroid. T3b: Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles) from a tumor of any size. T4: Tumor of any size with gross extrathyroidal extension. N1: Metastasis to regional nodes. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVC includes: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage IVA includes: (T4a, Any N, M0); (T1-3, N1b, M0). T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but less than 4 cm in greatest dimension limited to the thyroid. T3: Tumor measuring 4 cm or more in greatest dimension or with extrathyroidal extension. T4a: Moderately advanced disease; tumor of any size with gross extrathyroidal extension into the nearby tissues of the neck, including subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve. N1b: Metastasis to unilateral, bilateral, or contralateral lateral neck lymph nodes levels I, II, III, IV, or V or retropharyngeal lymph nodes. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVB includes: T4b, Any N, M0. T4b: Very advanced disease; tumor of any size with extension towards the spine or into nearby large blood vessels, invading the prevertebral fascia, or encasing the carotid artery or mediastinal vessels. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Tumor measuring 5 cm or less in greatest dimension, with no extra-adrenal invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
A rare genetic heart-hand syndrome with characteristics of typical manifestations of the Carney complex (spotty pigmentation of the skin, familial cardiac and cutaneous myxomas and endocrinopathy) associated with trismus and distal arthrogryposis (presenting as involuntary contraction of distal and proximal interphalangeal joints of hands evident only on dorsiflexion of wrist and similar lower-limb contractures producing foot deformities).
A disorder characterized by dryness of the cornea and conjunctiva.
A disorder characterized by reduced salivary flow in the oral cavity.
A disorder characterized by blockage of the normal flow of stomach contents through the duodenum.
A disorder characterized by a rupture in the duodenal wall.
A disorder characterized by a narrowing of the lumen of the duodenum.
A disorder characterized by slow and slurred speech resulting from an inability to coordinate the muscles used in speech.
A disorder characterized by abnormally painful abdominal cramps during menses.
A disorder characterized by swelling due to an accumulation of excessive fluid in the neck.
A disorder characterized by a sensation of marked discomfort in the neck area.
A disorder characterized by symptoms that include severe edema, proteinuria, and hypoalbuminemia; it is indicative of renal dysfunction.
A disorder characterized by a discrepancy between the lengths of the lower or upper extremities.
An adverse drug reaction, whose nature, severity, specificity, or outcome is not consistent with the term or description used in the applicable product information (e.g., IB for an unapproved investigational product or PI/summary of product characteristics for an approved product, and/or scientific literature). (ICH)
A disorder characterized by blockage of the normal flow of the contents of the intestinal stoma.
A finding of damage to the urinary system during a surgical procedure.
A disorder characterized by bleeding from the upper gastrointestinal tract (oral cavity, pharynx, esophagus, and stomach).
A disorder characterized by a blood clot and inflammation involving a superficial vein of the extremities.
A disorder characterized by an infectious process involving the urethra.
A disorder characterized by an abnormal communication between any part of the urinary system and another organ or anatomic site.
A disorder characterized by urination at short intervals.
A disorder characterized by inability to control the flow of urine from the bladder.
A disorder characterized by a high-pitched, whistling sound during breathing. It results from the narrowing or obstruction of the respiratory airways.
A disorder characterized by an infectious process involving the wound.
A finding of traumatic injury to the wrist joint in which the continuity of a wrist bone is broken.
A disorder characterized by laboratory test results that indicate complete absence of spermatozoa in the semen.
A disorder characterized by a sensation of marked discomfort in the back region.
A disorder characterized by the presence of bacteria in the blood stream.
A disorder characterized by a group of symptoms similar to those observed in patients with the flu. It includes fever, chills, body aches, malaise, loss of appetite and dry cough.
A finding based on test results that indicate a relative decrease in the fraction of the forced vital capacity that is exhaled in a specific number of seconds.
A disorder characterized by the presence of fungus in the blood stream.
A disorder characterized by impairment of verbal communication skills, often resulting from brain damage.
A disorder characterized by painful urination.
A disorder characterized by skin which becomes itchy, red, inflamed, crusty, thick, scaly, and/or forms blisters.
A disorder characterized by swelling due to an excessive accumulation of fluid in the brain.
A disorder characterized by swelling due to excessive fluid accumulation in facial tissues.
A disorder characterized by swelling due to excessive fluid accumulation in the trunk area.
A disorder characterized by a thickening of the outer layer of the skin.
A disorder characterized by an increase in production of parathyroid hormone by the parathyroid glands. This results in hypercalcemia (abnormally high levels of calcium in the blood).
A disorder characterized by characterized by excessive sleepiness during the daytime.
A disorder characterized by dysfunction of the hypoglossal nerve (twelfth cranial nerve).
A disorder characterized by laboratory test results that indicate a low concentration of potassium in the blood.
A disorder characterized by laboratory test results that indicate a low concentration of sodium in the blood.
A disorder characterized by inflammation and cellular infiltration of the pituitary gland.
A disorder characterized by a decrease in production of hormones from the pituitary gland.
A disorder characterized by a malformation of the nipple.
A disorder characterized by a sensation of marked discomfort in the chest unrelated to a heart disorder.
A disorder characterized by a sensation of marked discomfort in the urinary tract.
A disorder characterized by a sudden compelling urge to urinate.
A finding based on test results that indicate urine production is less relative to previous output.
A finding of leakage of contents from a urostomy.
A disorder characterized by bleeding from the urostomy site.
A finding of narrowing of the opening of a urostomy.
Uterine corpus adenosarcoma with distant metastasis (excluding adnexa, pelvic, and abdominal tissues). (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with regional lymph node metastasis (greater than 2.0 mm in diameter) to pelvic lymph nodes. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with regional lymph node metastasis (greater than 0.2 mm but nor greater than 2.0 mm in diameter) to pelvic lymph nodes. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with regional lymph node metastasis to pelvic lymph nodes. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with regional lymph node metastasis (greater than 2.0 mm in diameter) to para-aortic lymph nodes, with or without positive pelvic lymph nodes. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with regional lymph node metastasis (greater than 0.2 mm but not greater than 2.0 mm in diameter) to para-aortic lymph nodes, with or without positive pelvic lymph nodes. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic lymph nodes. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease, lung, liver, or bone. It excludes metastasis to pelvic or para-aortic lymph nodes, vagina, uterine serosa, or adnexa). (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with distant metastasis (excluding adnexa, pelvic, and abdominal tissues). (from AJCC 8th Ed.)
A finding based on laboratory test results that indicate abnormal levels of gonadotrophin hormone in a blood specimen.
A finding based on laboratory test results that indicate abnormal levels of growth hormone in a biological specimen.
A disorder characterized by a dysrhythmia without discernible QRS complexes due to rapid repetitive excitation of myocardial fibers without coordinated contraction of the ventricles.
A disorder characterized by a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo).
Isomerism in the context of the congenitally malformed heart is defined as a situation where some paired structures on opposite sides of the left-right axis of the body are, in morphologic terms, symmetrical mirror images of each other. [PMID:21731561]
A disorder characterized by a narrowing of the lumen of the bile duct.
A disorder characterized by a rupture in the bladder wall.
A disorder characterized by a necrotic process occurring in the gallbladder.
A disorder characterized by a sensation of marked discomfort in the gallbladder region.
A disorder characterized by a rupture in the gallbladder wall.
A finding of leakage due to breakdown of a gastric anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by an abnormal communication between the stomach and another organ or anatomic site.
A disorder characterized by a necrotic process occurring in the gastric wall.
A disorder characterized by a rupture in the stomach wall.
A disorder characterized by a narrowing of the lumen of the stomach.
A disorder characterized by an abnormal communication between any part of the gastrointestinal system and another organ or anatomic site.
A disorder characterized by problems related to ejaculation. This category includes premature, delayed, retrograde and painful ejaculation.
The percentage computed when the amount of blood ejected during a ventricular contraction of the heart is compared to the amount that was present prior to the contraction.
A disorder characterized by a pathologic process involving the brain.
A disorder characterized by an infectious process involving the endocardial layer of the heart.
A disorder characterized by inflammation of the small and large intestines.
A disorder characterized by an infectious process involving the small and large intestines.
A disorder characterized by an abnormal communication between the urinary bladder and the intestine.
A disorder characterized by involuntary movements of the eyeballs.
A disorder characterized by dysfunction of the olfactory nerve (first cranial nerve).
A disorder characterized by dysfunction of the glossopharyngeal nerve (ninth cranial nerve).
A finding of damage to a vein during a surgical procedure.
A disorder characterized by a narrowing of the lumen of the esophagus.
A disorder characterized by an abnormal communication between the oral cavity and another organ or anatomic site.
A disorder characterized by a burning or tingling sensation on the lips, tongue or entire mouth.
A disorder characterized by a sudden and involuntary contraction of the bladder wall.
A finding based on laboratory test results that indicate abnormal levels of antidiuretic hormone in the blood specimen.
A finding based on laboratory test results that indicate abnormal levels of prolactin hormone in a blood specimen.
A disorder characterized by an abnormal body smell resulting from the growth of bacteria on the body.
A disorder characterized by the inability of the bone marrow to produce hematopoietic elements.
A disorder characterized by a sensation of marked discomfort in the bones.
A disorder characterized by regional paresthesia of the brachial plexus, marked discomfort and muscle weakness, and limited movement in the arm or hand.
A brain glioblastoma that occurs during childhood.
A disorder characterized by a sensation of marked discomfort in the gastrointestinal region.
A disorder characterized by a necrotic process occurring in the gastrointestinal tract stoma.
Gestational trophoblastic neoplasm with lung metastasis. (from AJCC 8th Ed.)
Gestational trophoblastic neoplasm with all other distant metastases. (from AJCC 8th Ed.)
A disorder characterized by target lesions (a pink-red ring around a pale center).
A finding of leakage due to breakdown of an esophageal anastomosis (surgical connection of two separate anatomic structures).
A disorder characterized by bleeding from the esophagus.
A disorder characterized by a necrotic process occurring in the esophageal wall.
A disorder characterized by blockage of the normal flow of the contents in the esophagus.
A disorder characterized by a circumscribed, erosive lesion on the mucosal surface of the esophageal wall.
A disorder characterized by bleeding from esophageal varices.
A disorder characterized by a rupture in the ileal wall.
Any agent that inhibits the activity of the orexin receptor.
A disorder characterized by a necrotic process occurring in the bone of the mandible.
A disorder characterized by an infectious process involving the ovary.
A disorder characterized by tearing or disruption of the ovarian tissue.
Ovarian, fallopian tube, or primary peritoneal carcinoma with distant metastasis, including pleural effusion with positive cytology; liver or splenic parenchymal metastasis; metastasis to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside the abdominal cavity); and transmural involvement of intestine. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with pleural effusion with positive cytology. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with liver or splenic parenchymal metastases; metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside the abdominal cavity); transmural involvement of intestine. (from AJCC 8th Ed.)
A disorder characterized by a sensation of marked discomfort in one side of the abdomen between menstrual cycles, around the time of the discharge of the ovum from the ovarian follicle.
A disorder characterized by less than 10% total body skin area separation of dermis. The syndrome is thought to be a hypersensitivity complex affecting the skin and the mucous membranes.
A disorder characterized by a sensation of marked discomfort in the stomach.
A disorder characterized by a circumscribed, erosive lesion on the jejunal mucosal surface close to the anastomosis site following a gastroenterostomy procedure.
An unexpected death that cannot be attributed to a CTCAE term associated with Grade 5.
A disorder characterized by thoughts of taking one's own life.
A disorder characterized by self-inflicted harm in an attempt to end one's own life.
A disorder characterized by fibrotic degeneration of the superficial soft tissues.
A disorder characterized by obstruction of the blood flow in the superior vena cava. Signs and symptoms include swelling and cyanosis of the face, neck, and upper arms, cough, orthopnea and headache.
A disorder of the white matter of the brain causing neurological problems, which can occur, anytime from childhood to adulthood. Characteristics of the disease include learning disabilities, retinopathy, atrophy of the optic nerves, spasticity, infertility in males, vertigo, tinnitus, hearing loss, paroxysmal kinesigenic dyskinesia and psychiatric disorders. In affected individuals, myelin becomes edematous causing impaired nerve impulse transmission. Caused by mutations in the CLCN2 gene. Inherited in an autosomal recessive pattern.
A disorder characterized by blockage of a bronchus passage, most often by bronchial secretions and exudates.
A disorder characterized by laboratory test results that indicate an increased number of eosinophils in the blood.
A disorder characterized by a sensation of marked discomfort in the buttocks.
A disorder characterized by stature that is smaller than normal as expected for age.
A disorder characterized by excessive development of the breasts in males.
A finding of damage to the carotid artery.
A finding based on laboratory test results that indicate an increase in the ratio of the patient's prothrombin time to a control sample in the blood.
A disorder characterized by a sensation of marked discomfort in the skin.
A disorder characterized by an infectious process involving the pancreas.
A finding of leakage due to breakdown of a pancreatic anastomosis (surgical connection of two separate anatomic structures).
A finding based on laboratory test results that indicate an decrease in levels of pancreatic enzymes in a biological specimen.
A disorder characterized by the presence of microangiopathic hemolytic anemia, thrombocytopenic purpura, fever, renal abnormalities and neurological abnormalities such as seizures, hemiplegia, and visual disturbances. It is an acute or subacute condition.
A disorder characterized by a pathological process of the teeth occurring during tooth development.
A disorder characterized by local dilatation of small vessels resulting in red discoloration of the skin or mucous membranes.
A disorder characterized by damage or dysfunction of the peripheral sensory nerves.
A disorder characterized by a sensation of marked discomfort in the testis.
A disorder characterized by episodic reddening of the skin, especially face, neck, or chest.
A finding based on laboratory test results that indicate an decrease in levels of haptoglobin in a blood specimen.
A disorder characterized by the inability of the heart to pump blood at an adequate volume to meet tissue metabolic requirements, or, the ability to do so only at an elevation in the filling pressure.
A finding based on laboratory test results that indicate increased levels of hemoglobin above normal.
A disorder characterized by laboratory test results that indicate the presence of free hemoglobin in the urine.
A disorder characterized by a form of thrombotic microangiopathy with renal failure, hemolytic anemia, and severe thrombocytopenia.
A disorder characterized by bleeding from the hemorrhoids.
A disorder characterized by the presence of dilated veins in the rectum and surrounding area.
A disorder characterized by bleeding from the liver.
A disorder characterized by an infectious process involving the liver.
A disorder characterized by a necrotic process occurring in the hepatic parenchyma.
A finding of leakage of contents from an intestinal stoma (surgically created opening on the surface of the body).
A disorder characterized by bleeding in the abdominal cavity.
A disorder characterized by bleeding from the cranium.
A finding of damage to an artery during a surgical procedure.
A finding of damage to the breast parenchyma during a surgical procedure.
A finding of damage to the heart during a surgical procedure.
A finding of damage to the endocrine gland during a surgical procedure.
A finding of damage to the gastrointestinal system during a surgical procedure.
A finding of damage to the head and neck during a surgical procedure.
A finding of uncontrolled bleeding during a surgical procedure.
A finding of damage to the nervous system during a surgical procedure.
A disorder characterized by a necrotic process occurring in the pancreas.
A disorder characterized by inflammation of the pancreas with no documented pancreas infection.
A disorder characterized by swelling around the optic disc.
A disorder characterized by an eruption consisting of papules (a small, raised pimple) and pustules (a small pus filled blister), typically appearing in face, scalp, and upper chest and back. Unlike acne, this rash does not present with whiteheads or blackheads, and can be symptomatic, with itchy or tender lesions.
A disorder characterized by a dysrhythmia with abrupt onset and sudden termination of atrial contractions with a rate of 150-250 beats per minute. The rhythm disturbance originates in the atria.
A disorder characterized by an infectious process involving the penis.
A disorder characterized by a sensation of marked discomfort in the penis.
A disorder characterized by noise in the ears, such as ringing, buzzing, roaring or clicking.
A disorder characterized by a change in tooth hue or tint.
A molecular genetic abnormality indicating the presence of a mutation in intron 13 of the MET gene.
A molecular genetic abnormality indicating the presence of a mutation in intron 14 of the MET gene.
A disorder characterized by repeated gulp sounds that result from an involuntary opening and closing of the glottis. This is attributed to a spasm of the diaphragm.
A disorder characterized by the presence of excess hair growth in women in anatomic sites where growth is considered to be a secondary male characteristic and under androgen control (beard, moustache, chest, abdomen).
A finding based on lung function test results that indicate a decrease in the lung capacity to absorb carbon monoxide.
A finding of leakage due to breakdown of an anastomosis (surgical connection of two separate anatomic structures) in the large intestine.
A disorder characterized by swelling due to an excessive accumulation of fluid in the larynx.
A disorder characterized by ulceration or inflammation involving the mucous membrane of the larynx.
A finding of damage to the eye during a surgical procedure.
A finding of damage to the reproductive organs during a surgical procedure.
A disorder characterized by a change in cycle or duration of menses from baseline.
A disorder characterized by an increase in intrapericardial pressure due to the collection of blood or fluid in the pericardium.
A disorder characterized by a sensation of marked discomfort in the area between the genital organs and the anus.
A disorder characterized by impaired circulation to an extremity.
A disorder characterized by an infectious process involving the peripheral nerves.
A disorder characterized by an infectious process involving the peritoneum.
A disorder characterized by a conspicuous change in a person's behavior and thinking.
A disorder characterized by ulceration or inflammation involving the mucous membrane of the pharynx.
A disorder characterized by an inflammation or ulceration involving the mucous membrane of the trachea.
A disorder characterized by a narrowing of the trachea.
A disorder characterized by bleeding from the tracheostomy site.
A disorder characterized by the uncontrolled shaking movement of the whole body or individual parts.
A disorder characterized by a decrease in joint flexibility of any joint.
A disorder characterized by an infectious process involving the abdominal cavity.
A disorder characterized by a sensation of marked discomfort in the abdominal region.
A disorder characterized by a necrotic process occurring in the soft tissues of the abdominal wall.
A disorder characterized by dysfunction of the abducens nerve (sixth cranial nerve).
A disorder characterized by dysfunction of the acoustic nerve (eighth cranial nerve).
A finding based on laboratory test results in which the partial thromboplastin time is found to be greater than the control value. As a possible indicator of coagulopathy, a prolonged partial thromboplastin time (PTT) may occur in a variety of diseases and disorders, both primary and related to treatment.
A disorder characterized by an infectious process that arises secondary to catheter use.
A finding based on laboratory test results that indicate an decrease in levels of CD4 lymphocytes in a blood specimen.
A disorder characterized by blockage of the laryngeal airway.
A disorder characterized by an inflammatory process involving the larynx.
A disorder characterized by paroxysmal spasmodic muscular contraction of the vocal cords.
A disorder characterized by a narrowing of the lumen of the jejunum.
A disorder characterized by excessive fluid in a joint, usually as a result of joint inflammation.
A disorder characterized by a decrease in flexibility of a lumbar spine joint.
A disorder characterized by paralysis of the recurrent laryngeal nerve.
A disorder characterized by a narrowing of the pharyngeal airway.
A disorder characterized by a sensation of marked discomfort in the pharyngolaryngeal region.
A disorder characterized by inflammation of the wall of a vein.
A disorder characterized by an infectious process involving the vein. Clinical manifestations include erythema, marked discomfort, swelling, and induration along the course of the infected vein.
A disorder characterized by fear and avoidance of light.
Transient eyelid retraction during refixation from down to straight ahead. [ORCID:0000-0003-0986-4123]
Primary food allergies primarily occur as a result (most likely) of gastrointestinal sensitization to predominantly stable food allergens (glycoproteins). A secondary food allergy develops after primary sensitization to airborne allergens (e. g., pollen allergens) with subsequent reactions (due to cross-reactivity) to structurally related often labile allergens in (plant) foods. [PMID:27069254, PMID:27069841]
A disorder characterized by laboratory test results that indicate a low concentration of albumin in the blood.
A disorder characterized by laboratory test results that indicate the presence of excessive protein in the urine. It is predominantly albumin, but also globulin.
A disorder characterized by a sensation of marked discomfort in the face, between the eyes, or upper teeth originating from the sinuses.
Fanconi anemia complementation group S is an autosomal recessive disorder characterized by developmental delay apparent from infancy, short stature, microcephaly, and coarse dysmorphic features. Laboratory studies show defective DNA repair and increased chromosomal breakage during stress. Some patients may have radial ray anomalies, anemia, and increased risk of cancer; patients often have a family history of cancer in family members who have heterozygous mutations (summary by Freire et al., 2018). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650.
A finding of injury of the soft tissues or bone characterized by leakage of blood into surrounding tissues.
A disorder characterized by a sensation of marked discomfort in the prostate gland.
A disorder characterized by an injury of the rotator cuff.
Amyloidosis cutis dyschromica (ACD), a rare form of primary localized cutaneous amyloidosis, is a pigmentary disorder in which keratinocyte-derived amyloid is deposited in the skin. Onset occurs before puberty and involves macular or reticulate hyperpigmentation admixed with symmetrically distributed guttate hypopigmented and hyperpigmented lesions. ACD can be distinguished from other conditions with similar clinical findings by a skin biopsy in which amyloid deposition in the papillary dermis is seen. Specific features that set ACD apart from the more common macular and lichenoid variants of primary cutaneous amyloidosis include dotted, reticular, or diffuse hyperpigmentation admixed with lentil-sized hypopigmented macules; mild or no associated pruritus; and, on histologic examination of skin from both hyper- and hypopigmented lesions, amyloid deposition confined to the papillary dermis, in close proximity to the epidermis (Huang et al. (2009); Mahon et al., 2016). For a discussion of genetic heterogeneity of primary localized cutaneous amyloidosis, see 105250.
A disorder characterized by a sensation of marked discomfort in the face.
A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates distal to the bundle of His.
A disorder characterized by a sensation of marked discomfort in the pelvis.
A rare primary cutaneous amyloidosis characterised by macular or reticulate hyperpigmentation with symmetrically distributed guttate hypo and hyperpigmented lesions which progress gradually over the years to involve almost the entire body (with relative sparing of the face, hands, feet and neck). Patients are usually asymptomatic, however mild pruritus may be associated. Amyloid deposition in the papillary dermis is observed on skin biopsy. Systemic amyloidosis is not present and association with generalised morphea, atypical Parkinsonism, spasticity, motor weakness or colon carcinoma is rare.
A disorder characterized by loss of cerebrospinal fluid into the surrounding tissues.
A disorder characterized by reduced bone mass, with a decrease in cortical thickness and in the number and size of the trabeculae of cancellous bone (but normal chemical composition), resulting in increased fracture incidence.
A disorder characterized by a sensation of marked discomfort in the breast region.
A disorder characterized by laboratory test results that indicate a low concentration of calcium (corrected for albumin) in the blood.
A disorder characterized by abnormal sensual experience with the taste of foodstuffs; it can be related to a decrease in the sense of smell.
A disorder characterized by difficulty in falling asleep and/or remaining asleep.
A disorder characterized by bleeding from the nose.
A disorder characterized by a defect in tricuspid valve function or structure.
A disorder characterized by personality change, impaired functioning, and loss of touch with reality. It may be a manifestation of schizophrenia, bipolar disorder or brain tumor.
A disorder characterized by laboratory test results that indicate blood in the urine.
A disorder characterized by obstruction of the nasal passage due to mucosal edema.
A disorder characterized by an abnormal increase in the curvature of the lumbar portion of the spine.
A disorder characterized by a reduction in the amount of hemoglobin in 100 ml of blood. Signs and symptoms of anemia may include pallor of the skin and mucous membranes, shortness of breath, palpitations of the heart, soft systolic murmurs, lethargy, and fatigability.
A disorder characterized by a decrease in the number of spermatozoa in the semen.
A disorder characterized by a decrease in production of parathyroid hormone by the parathyroid glands.
A disorder characterized by laboratory test results that indicate an elevation in the concentration of sodium in the blood.
A disorder characterized by laboratory test results that indicate a low concentration of phosphates in the blood.
A disorder characterized by an infectious process involving the urinary tract, most commonly the bladder and the urethra.
A disorder characterized by lack of coordination of muscle movements resulting in the impairment or inability to perform voluntary activities.
A disorder characterized by a sensation of marked discomfort in the mouth, tongue or lips.
A disorder characterized by a brief attack (less than 24 hours) of cerebral dysfunction of vascular origin, with no persistent neurological deficit.
A disorder characterized by dysfunction of the trochlear nerve (fourth cranial nerve).
A disorder characterized by excessive mucous secretion in the back of the nasal cavity or throat, causing sore throat and/or coughing.
A disorder characterized by spontaneous loss of consciousness caused by insufficient blood supply to the brain.
A disorder characterized by a state of generalized weakness with a pronounced inability to summon sufficient energy to accomplish daily activities.
A disorder characterized by fluid collection within the pericardial sac, usually due to inflammation.
A disorder characterized by laboratory test results that indicate an elevation in the concentration of magnesium in the blood.
A disorder characterized by vaginal secretions. Mucus produced by the cervical glands is discharged from the vagina naturally, especially during the childbearing years.
A disorder characterized by laboratory test results that indicate an elevation in the concentration of phosphate in a blood.
A disorder characterized by a tear in the lining of the anus.
A disorder characterized by fluid accumulation in the tissues of the body including the skin.
A disorder characterized by an increase in thyroid stimulating hormone.
A disorder characterized by Electrocardiogram T wave amplitude changes.
A finding based on laboratory test results that indicate increased levels of lactate dehydrogenase in the blood specimen.
A disorder characterized by a necrotic process occurring in the soft tissues of the chest wall including breast.
A disorder characterized by bleeding in a tumor.
A disorder characterized by less than normal deep tendon reflexes.
A disorder that occurs after the injection of a substance with antigenic properties, administered to activate the immune system.
A disorder characterized by occlusion of an arterial vessel by a blood clot that develops in an artery.
A disorder characterized by a tear in the lining of the rectum.
A disorder characterized by an infectious process involving the brain tissue.
A disorder characterized by the reactivation of Herpes simplex virus
A disorder characterized by the reactivation of hepatitis B virus.
A disorder characterized by the reactivation of Epstein-Barr virus (EBV).
A disorder characterized by the reactivation of cytomegalovirus (CMV).
A disorder characterized by a change in the way the hair feels.
A disorder characterized by low testosterone.
A disorder characterized by lymph node enlargement after vaccination
A disorder characterized by a sensation of marked discomfort in the oropharynx.
A disorder characterized by partial or complete opacity of the crystalline lens of one or both eyes. This results in a decrease in visual acuity and eventual blindness if untreated.
A disorder characterized by a lack of clear and orderly thought and behavior.
A disorder characterized by laboratory test results that indicate an elevation in the concentration of lipids in blood.
A disorder characterized by cessation of breathing for short periods during sleep.
An antisense oligonucleotide targeting signal transducer and activator of transcription 3 (STAT3) with potential antitumor activity. Danvatirsen binds to STAT3 mRNA, thereby inhibiting translation of the transcript. Suppression of STAT3 expression induces tumor cell apoptosis and decreases tumor cell growth. STAT3, a protein overexpressed in a variety of human cancers, plays a critical role in tumor cell growth and survival.
A small molecule inhibitor of the BET (Bromodomain and Extra-Terminal) family of bromodomain-containing proteins with potential antineoplastic activity. Upon administration, molibresib binds to the acetylated lysine recognition motifs on the bromodomain of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histone peptides. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth. Characterized by a tandem repeat of bromodomain at the N-terminus, BET proteins, comprising of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.
A human monoclonal antibody directed against the human epidermal growth factor receptor HER3 (ErbB3) with potential antineoplastic activity. Elgemtumab binds to and locks HER3 in the inactive conformation and does not interfere with its interaction with neuregulin (NRG). The inactivated form of HER3 blocks the PI3K/Akt signaling pathway, thereby inhibiting cellular proliferation in HER2 or NRG expressing tumor cells. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors; it has no active kinase domain but is activated through heterodimerization with other members of the EGFR receptor family, such as HER2.
An orally bioavailable combination agent composed of the cytotoxic pyrimidine analog trifluridine (5-trifluoro-2'-deoxythymidine or TFT) and a thymidine phosphorylase inhibitor (TPI) tipiracil hydrochloride, in a molar ratio of 1.0:0.5 (TFT:TPI), with potential antineoplastic activity. After oral administration of TAS-102, TFT is phosphorylated to the active monophosphate form TF-TMP, which binds covalently to the active site of thymidylate synthase, thereby reducing the nucleotide pool levels required for DNA replication. Furthermore, the triphosphate form TF-TTP can be incorporated into DNA, which induces DNA fragmentation and leads to the inhibition of tumor growth. TPI exhibits a dual effect: 1) an anti-angiogenic effect mediated through the inhibition of thymidine phosphorylase, which plays important role in nucleotide metabolism and a variety of development processes, including angiogenesis, 2) increased bioavailability of the normally short-lived antimetabolite TFT by preventing its degradation into the inactive form trifluorothymine (TF-Thy). The synergistic effect of the components in TAS-10 may demonstrate antitumor activity in 5-FU-resistant cancer cells.
A novel pyrrolopyrimidine derivative, and an orally available inhibitor of the serine/threonine protein kinase AKT (protein kinase B) with potential antineoplastic activity. Capivasertib binds to and inhibits all AKT isoforms. Inhibition of AKT prevents the phosphorylation of AKT substrates that mediate cellular processes, such as cell division, apoptosis, and glucose and fatty acid metabolism. A wide range of solid and hematological malignancies show dysregulated PI3K/AKT/mTOR signaling due to mutations in multiple signaling components. By targeting AKT, the key node in the PIK3/AKT signaling network, this agent may be used as monotherapy or combination therapy for a variety of human cancers.
The hydrochloride salt form of ulimorelin, a macrocyclic ghrelin peptidomimetic, with potential gastrointestinal (GI) prokinetic activity. Upon intravenous administration, ulimorelin binds to the ghrelin receptor in the GI tract and may stimulate GI motility. Ghrelin is a natural ligand for growth hormone secretagogue receptors and is normally localized in the proximal GI tract. The ghrelin receptor signaling pathway mediates multiple GI functions, including motility and gastric emptying.
An inhibitor of the beta and delta isoforms of the 110 kDa catalytic subunit of class IA phosphoinositide-3 kinases (PI3K) with potential immunomodulating and antineoplastic activities. Acalisib inhibits the activity of PI3K, thereby preventing the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), which decreases tumor cell proliferation and induces cell death. PI3K-mediated signaling is often dysregulated in cancer cells; the targeted inhibition of PI3K is designed to preserve PI3K signaling in normal, non-neoplastic cells.
An orally bioavailable inhibitor of both phosphoinositide 3-kinase (PI3K) class I and pan histone deacetylase (HDAC) enzymes, with potential antineoplastic activity. Upon oral administration, fimepinostat inhibits the activity of both PI3K class I isoforms and HDAC, thereby preventing the activation of the PI3K-AKT-mTOR signal transduction pathway that is often overactivated in many cancer cell types. This may prevent growth of PI3K and/or HDAC-expressing tumor cells. CUDC-907 shows an increased inhibition of tumor cell growth and induction of apoptosis when compared to inhibitors that target either PI3K or HDAC.
An orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. Derazantinib binds to and potently inhibits the activity of FGFR subtypes 1, 2 and 3. This may result in the inhibition of FGFR-mediated signal transduction pathways, tumor cell proliferation, tumor angiogenesis and tumor cell death in FGFR-overexpressing tumor cells. FGFR, a receptor tyrosine kinase, is upregulated in many tumor cell types and plays a key role in tumor cellular proliferation, differentiation, angiogenesis and survival.
An orally bioavailable, selective inhibitor of the delta isoform of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinases (PI3K) with potential antineoplastic activity. PI3K-delta inhibitor TGR-1202 inhibits PI3K and prevents the activation of the PI3K/AKT kinase signaling pathway. This decreases proliferation and induces cell death in susceptible tumor cells. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in tumor cells and cells of the hematopoietic lineage. The targeted inhibition of PI3K-delta allows for PI3K signaling in normal, non-neoplastic cells. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival.
An orally available, nonsteroidal selective estrogen receptor degrader (SERD), with potential antineoplastic activity. Upon oral administration, brilanestrant binds to the estrogen receptor and induces a conformational change that results in the degradation of the receptor. This may inhibit the growth and survival of ER-expressing cancer cells.
An orally bioavailable, selective inhibitor of the delta isoform of the 110 kDa catalytic subunit of class I phosphoinositide-3 kinases (PI3K) with potential antineoplastic activity. Dezapelisib specifically inhibits PI3Kdelta, which prevents both the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) and the activation of the PI3K/AKT kinase signaling pathway. This decreases proliferation and induces cell death in PI3K-overexpressing tumor cells. Unlike other isoforms of PI3K, PI3Kdelta is often overexpressed in tumor cells, especially those of hematologic origin, and plays a crucial role in tumor cell regulation and survival. The targeted inhibition of PI3Kdelta allows for PI3K signaling in normal, non-neoplastic cells.
An orally bioavailable pan inhibitor of phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. Bimiralisib inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy. As mTOR, a serine/threonine kinase downstream of PI3K, may also be activated independent of PI3K, this agent may potentially be more potent than an agent that inhibits either PI3K kinase or mTOR kinase. By inhibiting mTOR to a lesser extent than PI3K, PQR309 does not interfere with the mTOR-mediated negative feedback loop on PI3K signaling. Blocking the negative feedback loop would potentially increase PI3K signaling and decrease therapeutic efficacy.
An orally available inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with potential immunomodulating and antineoplastic activities. Upon administration, navoximod targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the essential amino acid tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, this agent increases tryptophan levels, restores the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells. IDO1 is overexpressed by a variety of tumor cell types and plays an important role in immunosuppression. Tryptophan depletion is associated with immunosuppression caused by T-cell suppression.
An orally available inhibitor of isocitrate dehydrogenase type 1 (IDH1), with potential antineoplastic activity. Upon administration, AG-120 specifically inhibits a mutated form of IDH1 in the cytoplasm, which inhibits the formation of the oncometabolite, 2-hydroxyglutarate (2HG). This may lead to both an induction of cellular differentiation and an inhibition of cellular proliferation in IDH1-expressing tumor cells. IDH1, an enzyme in the citric acid cycle, is mutated in a variety of cancers; it initiates and drives cancer growth by both blocking cell differentiation and catalyzing the formation of 2HG.
An orally bioavailable, selective inhibitor of the serine/threonine monopolar spindle 1 (Mps1) kinase, with potential antineoplastic activity. Upon administration, empesertib binds to and inhibits the activity of Mps1. This causes inactivation of the spindle assembly checkpoint (SAC), accelerated mitosis, chromosomal misalignment, chromosomal missegregation, mitotic checkpoint complex destabilization, and increased aneuploidy. This leads to the induction of cell death in cancer cells overexpressing Mps1. Mps1, a kinase expressed in proliferating normal tissues and aberrantly overexpressed in a wide range of human tumors, is activated during mitosis and is essential for SAC functioning and controls chromosome alignment.
An orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic activity. Upon oral administration, vactosertib inhibits the activity of TGFBR1 and prevents TGF-beta/TGFBR1-mediated signaling. This suppresses tumor growth in TGFBR1-overexpressing tumor cells. TGFBR1, which is overexpressed in a variety of tumor cell types, plays a key role in tumor cell proliferation. Expression of TGF-beta promotes tumor cell proliferation, enhances the migration of tumor cells and suppresses the response of the host immune system to tumor cells.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody directed against the sodium-dependent phosphate transport protein 2B (NaPi2b), and covalently linked to monomethyl auristatin E (MMAE), an auristatin derivative and a potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration, the monoclonal antibody moiety of DNIB0600A binds to NaPi2b-expressing tumor cells and is internalized, thereby delivering MMAE intracellularly. Proteolytic cleavage releases MMAE, which then binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and tumor cell apoptosis. NaPi2b, a tumor-associated antigen (TAA), overexpressed in a variety of cancer cell types, plays a key role in transport of inorganic phosphate and the maintenance of phosphate homeostasis.
An orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, fenebrutinib inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways, which leads to the inhibition of the growth of malignant B-cells that overexpress BTK. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B-lymphocyte development, activation, signaling, proliferation and survival.
A synthetic, glycomimetic molecule and E-selectin (CD62E) antagonist, with potential anti-thrombotic, antineoplastic and chemopotentiating activities. Upon administration, uproleselan binds to E-selectin expressed on endothelial cells and prevents their interaction with selectin-E ligand-expressing cancer cells. This may prevent tumor cell activation, migration and metastasis. GMI-1271 also interferes with the binding of selectin E-expressing vascular endothelial cells to selectin-E ligand-expressing monocytes and neutrophils, thereby disrupting their activation. Consequently, this inhibits both the activation of the coagulation cascade and thrombus formation. This agent also prevents both leukocyte activation and inflammation. E-selectin is a cell adhesion molecule involved in cell rolling, signaling and chemotaxis; it also plays a crucial role in inflammatory processes and cancer.
An orally available, selective estrogen receptor degrader (SERD) and selective estrogen receptor modulator (SERM), with potential antineoplastic and estrogen-like activities. Upon oral administration of higher doses of RAD1901, this agent acts as a SERD, which binds to the estrogen receptor (ER) and induces a conformational change that results in the degradation of the receptor. This may inhibit the growth and survival of ER-expressing cancer cells. At lower doses of this agent, RAD1901 acts as a SERM and has estrogen-like effects in certain tissues, which can both reduce hot flashes and protect against bone loss. In addition, RAD1901 is able to cross the blood-brain barrier (BBB).
An orally available inhibitor of the epidermal growth factor receptor (EGFR) mutant form T790M, with potential antineoplastic activity. Mavelertinib specifically binds to and inhibits EGFR T790M, a secondary acquired resistance mutation, which prevents EGFR-mediated signaling and leads to cell death in EGFR/T790M-expressing tumor cells. Compared to some other EGFR inhibitors, PF-06747775 may have therapeutic benefits in tumors with T790M-mediated drug resistance. This agent shows minimal activity against wild-type EGFR (WT EGFR), and does not cause dose-limiting toxicities that occur during the use of non-selective EGFR inhibitors, which can inhibit WT EGFR. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization.
A humanized monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1), with immune checkpoint inhibitory and antineoplastic activities. Upon administration, spartalizumab binds to PD-1 expressed on activated T-cells and blocks the interaction with its ligands, programmed cell death 1 ligand 1 (PD-L1, PD-1L1) and PD-1 ligand 2 (PD-L2, PD-1L2). The inhibition of ligand binding prevents PD-1-mediated signaling and results in both T-cell activation and the induction of T-cell-mediated immune responses against tumor cells. PD-1, an immunoglobulin (Ig) superfamily transmembrane protein and inhibitory receptor, negatively regulates T-cell activation.
A monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1,) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-1 monoclonal antibody SHR-1210 binds to and blocks the binding of PD-1, expressed on activated T-lymphocytes, B-cells and natural killer (NK) cells, to its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen presenting cells (APCs). This prevents the activation of PD-1 and its downstream signaling pathways. This restores immune function through the activation of cytotoxic T-lymphocytes (CTLs) and cell-mediated immune responses against tumor cells or pathogens. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.
A humanized monoclonal antibody directed against the tyrosine kinase receptor colony stimulating factor 1 receptor (CSF1R; CSF-1R), also known as macrophage colony-stimulating factor receptor (M-CSFR) and CD115 (cluster of differentiation 115), with potential antineoplastic activity. Upon administration, anti-CSF1R monoclonal antibody FPA008 binds to CSF1R expressed on monocytes, macrophages, and osteoclasts and inhibits the binding of the CSF1R ligands colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34), to CSF1R. This prevents CSF1R activation and CSF1R-mediated signaling in these cells. This blocks the production of inflammatory mediators by macrophages and monocytes and reduces inflammation. By blocking the recruitment to the tumor microenvironment and activity of CSF1R-dependent tumor-associated macrophages (TAMs), FPA008 enhances T-cell infiltration and antitumor T-cell immune responses, which inhibits the proliferation of tumor cells. Additionally, FPA008 prevents the activation of osteoclasts and blocks bone destruction. TAMs play key roles in immune suppression and promoting inflammation, tumor cell proliferation and survival.
A bifunctional fusion protein composed of avelumab, an anti-programmed death ligand 1 (PD-L1) human monoclonal antibody, bound to the soluble extracellular domain of human transforming growth factor beta (TGFbeta) receptor type II (TGFbetaRII), with potential antineoplastic and immune checkpoint modulating activities. Upon administration, the TGFbetaRII moiety of M7824 binds to and neutralizes TGFbeta while the avelumab moiety simultaneously binds to PD-L1. This prevents TGFbeta- and PD-L1-mediated signaling, and increases natural killer (NK) cell and cytotoxic T-lymphocyte (CTL) activities. This inhibits tumor cell proliferation in susceptible tumor cells. TGFbeta and PD-L1 are both upregulated in certain types of cancers; their overexpression is associated with increased evasion of immune surveillance and contributes to poor prognosis.
An orally bioavailable, small molecule inhibitor of the acetate form of ralaniten, a N-terminal domain (NTD) of the androgen receptor (AR), with potential antineoplastic activity. Upon oral administration of ralaniten acetate, ralaniten specifically binds to the NTD of AR, thereby inhibiting both AR activation and the AR-mediated signaling pathway. This inhibits cell growth in AR-overexpressing tumor cells. AR is overexpressed in prostate cancers and is involved in proliferation, survival and chemoresistance of tumor cells.
An orally bioavailable inhibitor of exportin-1 (XPO1; chromosome region maintenance 1 protein homolog; CRM1), with potential antineoplastic activity. Upon administration, eltanexor binds to the XPO1 cargo binding site, which prevents the XPO1-mediated nuclear export of cargo proteins such as tumor suppressor proteins (TSPs), including p53, p73, BRCA1/2, pRB, FOXO, and other growth regulatory proteins and leads to their selective accumulation in the nuclei of tumor cells. As a selective inhibitor of nuclear export (SINE), KPT-8602 restores the nuclear localization and function of tumor suppressing proteins which leads to the induction of apoptosis in tumor cells. XPO1, the major export factor that transports proteins from the nucleus to the cytoplasm, is overexpressed in a variety of cancer cell types while minimally expressed in normal, healthy cells. The export of tumor suppressor proteins into the cytoplasm prevents them from initiating apoptosis and leads to uncontrolled tumor cell proliferation.
An orally available second-generation, reversible inhibitor of Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon administration, vecabrutinib non-covalently binds to and inhibits the activity of both wild-type and the C481S mutated form of BTK, a resistance mutation in the BTK active site in which cysteine is substituted for serine at residue 481. This prevents the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B-cells that overexpress BTK. Compared to other BTK inhibitors, SNS-062 does not require interaction with the BTK C481 site and inhibits the proliferation of cells harboring the BTK C481S mutation. Other irreversible BTK inhibitors covalently bind to the C481 site to inhibit BTK's activity; the C481S mutation prevents that binding. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes.
A finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to all carcinomas of the vagina. There is no AJCC staging system for mucosal melanoma of the vagina. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Vaginal cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Vaginal cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. The definitions of the T categories correspond to the stages accepted by FIGO. (from AJCC 8th Ed.)
Vaginal cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Vaginal cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Vaginal cancer with tumor invading the mucosa of the bladder or rectum and/or extending beyond the true pelvis (bullous edema is not sufficient evidence to classify a tumor as T4). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of vaginal cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Vaginal cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Vaginal cancer with no regional lymph node metastasis. (from AJCC 8th Ed.)
Vaginal cancer with isolated tumor cells in regional lymph node(s) no greater than 0.2 mm. (from AJCC 8th Ed.)
A term that refers to the staging of vaginal cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to all carcinomas of the vagina. There is no AJCC staging system for mucosal melanoma of the vagina. (from AJCC 8th Ed.)
Stage IB includes: T1b, N0, M0. T1b: Tumor confined to the vagina, measuring more than 2.0 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIA includes: T2a, N0, M0. T2a: Tumor invading paravaginal tissues but not to pelvic wall, measuring 2.0 cm or less. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIB includes: T2b, N0, M0. T2b: Tumor invading paravaginal tissues but not to pelvic wall, measuring more than 2.0 cm. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
A disease state that refers to a limited number of clinically detectable metastases, an intermediate state between purely localized disease and widespread metastases.
A response indicating that an individual used a smartphone or tablet other than their own, a friend or family member's, or the clinic's.
Histologic transformation of an indolent follicular non-Hodgkin lymphoma to an aggressive diffuse large B-cell lymphoma.
A finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Cervical cancer in which there is no evidence of distant metastasis. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Cervical cancer in which primary tumor cannot be assessed. (from AJCC 8th Ed.)
Cervical cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Cervical cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Invasive cervical carcinoma diagnosed only by microscopy. Stromal invasion with a maximum depth of 5.0 mm measured from the base of the epithelium and a horizontal spread of 7.0 mm or less. Vascular space involvement, venous or lymphatic, does not affect classification. (from AJCC 8th Ed.)
Invasive cervical carcinoma with measured stromal invasion of 3.0 mm or less in depth and 7.0 mm or less in horizontal spread. (from AJCC 8th Ed.)
Invasive cervical carcinoma with measured stromal invasion of more than 3.0 mm and not more than 5.0 mm, with a horizontal spread of 7.0 mm or less. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of cervical cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Cervical cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Cervical cancer with no regional lymph node metastasis. (from AJCC 8th Ed.)
Cervical cancer with isolated tumor cells in regional lymph node(s) no greater than 0.2 mm. (from AJCC 8th Ed.)
Cervical cancer with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of cervical cancer according to the American Joint Committee on Cancer, 8th edition.
A clinical finding about one or more characteristics of uterine corpus carcinoma or carcinosarcoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of uterine corpus carcinoma or carcinosarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Uterine corpus carcinoma or carcinosarcoma without evidence of distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of uterine corpus carcinoma or carcinosarcoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of uterine corpus carcinoma or carcinosarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of uterine corpus carcinoma or carcinosarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. The definitions of the T categories correspond to the stages accepted by FIGO. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with tumor confined to the corpus uteri, including endocervical glandular involvement. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with tumor limited to the endometrium or invading less than half the myometrium. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with tumor invading one half or more of the myometrium. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with tumor invading the stromal connective tissue of the cervix but not extending beyond the uterus. Does not include endocervical glandular involvement. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with tumor involving serosa, adnexa, vagina, or parametrium. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with tumor involving the serosa and/or adnexa (direct extension or metastasis). (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with vaginal involvement (direct extension or metastasis) or parametrial involvement. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with tumor invading the bladder mucosa and/or bowel mucosa (bullous edema is not sufficient to classify a tumor as T4). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of uterine corpus carcinoma or carcinosarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Uterine corpus carcinoma or carcinosarcoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with no regional lymph node metastasis. (from AJCC 8th Ed.)
Uterine corpus carcinoma or carcinosarcoma with isolated tumor cells in regional lymph node(s) no greater than 0.2 mm. (from AJCC 8th Ed.)
A semi-quantitative microscopic finding indicating that 50 percent or less of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A blood concentration of prostate specific antigen that is greater than 0.1 ng/mL.
A blood concentration of prostate specific antigen greater than or equal to 5 ng/mL.
A change in the nucleotide sequence of the PTPN11 gene that that results in constitutive activation of both tyrosine-protein phosphatase non-receptor type 11 and its downstream signaling pathways.
A change in the nucleotide sequence of the BRAF gene that that results in constitutive activation of both serine/threonine-protein kinase B-raf and its downstream signaling pathways.
A change in the nucleotide sequence of the NRAS gene that that results in constitutive activation of both oncogene N-Ras protein and its downstream signaling pathways.
A change in the nucleotide sequence of the HRAS gene that that results in constitutive activation of both oncogene H-Ras protein and its downstream signaling pathways.
An antibody-drug conjugate (ADC) consisting of an engineered version of the humanized monoclonal anti-human epidermal growth factor receptor 2 (HER2) immunoglobulin G1 (IgG1) trastuzumab that is site-specifically conjugated, via a cleavable linker, to the cytotoxic, DNA cross-linking pyrrolobenzodiazepine (PBD) dimer-based drug tesirine, which targets DNA minor grooves, with potential antineoplastic activity. Upon administration, the trastuzumab moiety of trastuzumab/tesirine ADC ADCT-502 targets the cell surface antigen HER2, which is expressed on various cancer cells. Upon antibody/antigen binding, internalization of the ADC and cleavage of the linker, the cytotoxic PBD moiety is released. The imine groups of tesirine bind to the N2 positions of guanines on opposite strands of DNA. This induces interstrand cross-links in the minor groove of DNA, inhibits DNA replication, leads to G2/M cell cycle arrest, induces cell death and inhibits the proliferation of HER2-overexpressing tumor cells. The tumor-associated antigen (TAA) HER2 is expressed by various solid tumors and is associated with a poor prognosis.
A term that refers to the staging of uterine corpus cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to carcinomas and carcinosarcomas. It does not apply to uterine corpus sarcomas: leiomyosarcomas, endometrial stromal sarcomas, and adenosarcomas. These sarcomas are staged according to the classification for uterine corpus sarcomas. (from AJCC 8th Ed.)
A finding about one or more characteristics of uterine corpus sarcoma, following the rules of the TNM AJCC v8 classification system. This classification system applies to sarcomas arising in the uterine corpus (leiomyosarcomas, endometrial stromal sarcomas, and adenosarcomas). Carcinosarcomas are staged according to the classification for uterine corpus carcinomas and carcinosarcomas. (from AJCC 8th Ed.)
A finding about one or more characteristics of uterine corpus leiomyosarcoma or endometrial stromal sarcoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of uterine corpus leiomyosarcoma or endometrial stromal sarcoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of uterine corpus leiomyosarcoma or endometrial stromal sarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma without evidence of distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of uterine corpus leiomyosarcoma or endometrial stromal sarcoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of uterine corpus leiomyosarcoma or endometrial stromal sarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of uterine corpus leiomyosarcoma or endometrial stromal sarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. The definitions of the T categories correspond to the stages accepted by FIGO. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor limited to the uterus. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor limited to the uterus, measuring 5 cm or less in greatest dimension. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor limited to the uterus, measuring more than 5 cm in greatest dimension. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor extending beyond the uterus, within the pelvis. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor extending beyond the uterus, within the pelvis and involving adnexa. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor involving other pelvic tissues. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor infiltrating abdominal tissues. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor infiltrating abdominal tissues at one site. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor infiltrating abdominal tissues at more than one site. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with tumor invading bladder or rectum. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of uterine corpus leiomyosarcoma or endometrial stromal sarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with no regional lymph node metastasis. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with isolated tumor cells in regional lymph node(s) no greater than 0.2 mm. (from AJCC 8th Ed.)
Uterine corpus leiomyosarcoma or endometrial stromal sarcoma with regional lymph node metastasis. (from AJCC 8th Ed.)
A finding about one or more characteristics of uterine corpus adenosarcoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of uterine corpus adenosarcoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of uterine corpus adenosarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Uterine corpus adenosarcoma without evidence of distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of uterine corpus adenosarcoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of uterine corpus adenosarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of uterine corpus adenosarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. The definitions of the T categories correspond to the stages accepted by FIGO. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor limited to the uterus. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor limited to the endometrium/endocervix. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor invading to less than half of the myometrium. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor invading more than half of the myometrium. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor extending beyond the uterus, within the pelvis. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor extending beyond the uterus, within the pelvis and involving adnexa. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor involving other pelvic tissues. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues at one site. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues at more than one site. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with tumor invading bladder or rectum. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of uterine corpus adenosarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Uterine corpus adenosarcoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with no regional lymph node metastasis. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with isolated tumor cells in regional lymph node(s) no greater than 0.2 mm. (from AJCC 8th Ed.)
Uterine corpus adenosarcoma with regional lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of uterine corpus sarcoma according to the American Joint Committee on Cancer, 8th edition. This staging system applies to leiomyosarcomas, endometrial stromal sarcomas, and adenosarcomas of the uterine corpus. It does not apply to carcinosarcomas which are staged according to the carcinomas and carcinosarcomas of the uterine corpus. (from AJCC 8th Ed.)
A term that refers to the staging of uterine corpus leiomyosarcoma according to the American Joint Committee on Cancer, 8th edition.
Stage I includes: T1, N0, M0. T1: Uterine corpus leiomyosarcoma with tumor limited to the uterus. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IA includes: T1a, N0, M0. T1a: Uterine corpus leiomyosarcoma with tumor limited to the uterus, measuring 5 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB includes: T1b, N0, M0. T1b: Uterine corpus leiomyosarcoma with tumor limited to the uterus, measuring more than 5 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Uterine corpus leiomyosarcoma with tumor extending beyond the uterus, within the pelvis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: IIIA: T3a, N0, M0; IIIB: T3b, N0, M0; IIIC: T1-3, N1, M0. T1: Uterine corpus leiomyosarcoma with tumor limited to the uterus. T2: Uterine corpus leiomyosarcoma with tumor extending beyond the uterus, within the pelvis. T3: Uterine corpus leiomyosarcoma with tumor infiltrating abdominal tissues. T3a: Uterine corpus leiomyosarcoma with tumor infiltrating abdominal tissues at one site. T3b: Uterine corpus leiomyosarcoma with tumor infiltrating abdominal tissues at more than one site. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA includes: T3a, N0, M0. T3a: Uterine corpus leiomyosarcoma with tumor infiltrating abdominal tissues at one site. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Uterine corpus leiomyosarcoma with tumor infiltrating abdominal tissues at more than one site. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIC includes: T1-3, N1, M0. T1: Uterine corpus leiomyosarcoma with tumor limited to the uterus. T2: Uterine corpus leiomyosarcoma with tumor extending beyond the uterus, within the pelvis. T3: Uterine corpus leiomyosarcoma with tumor infiltrating abdominal tissues. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IV includes: IVA: T4, Any N, M0; IVB: Any T, Any N, M1. T4: Uterine corpus leiomyosarcoma with tumor invading bladder or rectum. M0: No distant metastasis. M1: Distant metastasis (excluding adnexa, pelvic, and abdominal tissues). (from AJCC 8th Ed.)
Stage IVA includes: T4, Any N, M0. T4: Uterine corpus leiomyosarcoma with tumor invading bladder or rectum. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage IVB includes: Any T, Any N, M1. M1: M1: Distant metastasis (excluding adnexa, pelvic, and abdominal tissues). (from AJCC 8th Ed.)
A term that refers to the staging of uterine corpus endometrial stroma sarcoma according to the American Joint Committee on Cancer, 8th edition.
Stage I includes: T1, N0, M0. T1: Uterine corpus endometrial stroma sarcoma with tumor limited to the uterus. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IA includes: T1a, N0, M0. T1a: Uterine corpus endometrial stroma sarcoma with tumor limited to the uterus, measuring 5 cm or less in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB includes: T1b, N0, M0. T1b: Uterine corpus endometrial stroma sarcoma with tumor limited to the uterus, measuring more than 5 cm in greatest dimension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Uterine corpus endometrial stroma sarcoma with tumor extending beyond the uterus, within the pelvis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: IIIA: T3a, N0, M0; IIIB: T3b, N0, M0; IIIC: T1-3, N1, M0. T1: Uterine corpus endometrial stroma sarcoma with tumor limited to the uterus. T2: Uterine corpus endometrial stroma sarcoma with tumor extending beyond the uterus, within the pelvis. T3: Uterine corpus endometrial stroma sarcoma with tumor infiltrating abdominal tissues. T3a: Uterine corpus endometrial stroma sarcoma with tumor infiltrating abdominal tissues at one site. T3b: Uterine corpus endometrial stroma sarcoma with tumor infiltrating abdominal tissues at more than one site. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA includes: T3a, N0, M0. T3a: Uterine corpus endometrial stroma sarcoma with tumor infiltrating abdominal tissues at one site. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Uterine corpus endometrial stroma sarcoma with tumor infiltrating abdominal tissues at more than one site. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIC includes: T1-3, N1, M0. T1: Uterine corpus endometrial stroma sarcoma with tumor limited to the uterus. T2: Uterine corpus endometrial stroma sarcoma with tumor extending beyond the uterus, within the pelvis. T3: Uterine corpus endometrial stroma sarcoma with tumor infiltrating abdominal tissues. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IV includes: IVA: T4, Any N, M0; IVB: Any T, Any N, M1. T4: Uterine corpus endometrial stroma sarcoma with tumor invading bladder or rectum. M0: No distant metastasis. M1: Distant metastasis (excluding adnexa, pelvic, and abdominal tissues). (from AJCC 8th Ed.)
Stage IVA includes: T4, Any N, M0. T4: Uterine corpus endometrial stroma sarcoma with tumor invading bladder or rectum. M0: No distant metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of uterine corpus adenosarcoma according to the American Joint Committee on Cancer, 8th edition.
Stage IA includes: T1a, N0, M0. T1a: Uterine corpus adenosarcoma with tumor limited to the endometrium/endocervix. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IB includes: T1b, N0, M0. T1b: Uterine corpus adenosarcoma with tumor invading to less than half of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IC includes: T1c, N0, M0. T1c: Uterine corpus adenosarcoma with tumor invading more than half of the myometrium. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Uterine corpus adenosarcoma with tumor extending beyond the uterus, within the pelvis. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: IIIA: T3a, N0, M0; IIIB: T3b, N0, M0; IIIC: T1-3, N1, M0. T1: Uterine corpus adenosarcoma with tumor limited to the uterus. T2: Uterine corpus adenosarcoma with tumor extending beyond the uterus, within the pelvis. T3: Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues. T3a: Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues at one site. T3b: Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues at more than one site. N0: No regional lymph node metastasis. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA includes: T3a, N0, M0. T3a: Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues at one site. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIB includes: T3b, N0, M0. T3b: Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues at more than one site. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIC includes: T1-3, N1, M0. T1: Uterine corpus adenosarcoma with tumor limited to the uterus. T2: Uterine corpus adenosarcoma with tumor extending beyond the uterus, within the pelvis. T3: Uterine corpus adenosarcoma with tumor infiltrating abdominal tissues. N1: Regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IV includes: IVA: T4, Any N, M0; IVB: Any T, Any N, M1. T4: Uterine corpus adenosarcoma with tumor invading bladder or rectum. M0: No distant metastasis. M1: Distant metastasis (excluding adnexa, pelvic, and abdominal tissues). (from AJCC 8th Ed.)
Stage IVA includes: T4, Any N, M0. T4: Uterine corpus adenosarcoma with tumor invading bladder or rectum. M0: No distant metastasis. (from AJCC 8th Ed.)
A finding about one or more characteristics of ovarian, fallopian tube, or primary peritoneal carcinoma, following the rules of the TNM AJCC v8 classification system. Nonepithelial primary ovarian cancers may be staged using this classification but should be reported separately. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of ovarian, fallopian tube, or primary peritoneal carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of ovarian, fallopian tube, or primary peritoneal carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Ovarian, fallopian tube, or primary peritoneal carcinoma without evidence of distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of ovarian, fallopian tube, or primary peritoneal carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of ovarian, fallopian tube, or primary peritoneal carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of ovarian, fallopian tube, or primary peritoneal carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. The definitions of the T categories correspond to the stages accepted by FIGO. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor limited to ovaries (one or both) or fallopian tube(s). (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor limited to one ovary (capsule intact) or fallopian tube surface; no malignant cells in ascites or peritoneal washings. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor limited to one or both ovaries (capsules intact) or fallopian tubes; no tumor on ovarian or fallopian tube surface; no malignant cells in ascites or peritoneal washings. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor limited to one or both ovaries or fallopian tubes, with any of the following: surgical spill, capsule ruptured before surgery or tumor on ovarian or fallopian tube surface, or malignant cells in ascites or peritoneal washings. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor limited to one or both ovaries or fallopian tubes, with surgical spill.
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor limited to one or both ovaries or fallopian tubes, with capsule ruptured before surgery or tumor on ovarian or fallopian tube surface. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor limited to one or both ovaries or fallopian tubes with malignant cells in ascites or peritoneal washings. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor involving one or both ovaries or fallopian tubes with pelvic extension below pelvic brim or primary peritoneal cancer. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with extension and/or implants on the uterus and/or fallopian tube(s) and/or ovaries. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with extension to and/or implants on other pelvic tissues. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with tumor involving one or both ovaries or fallopian tubes, or primary peritoneal cancer, with microscopically confirmed peritoneal metastasis outside the pelvis and/or metastasis to the retroperitoneal (pelvic and/or para-aortic) lymph nodes. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with macroscopic peritoneal metastasis beyond pelvis 2 cm or less in greatest dimension with or without metastasis to the retroperitoneal lymph nodes. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with macroscopic peritoneal metastasis beyond the pelvis more than 2 cm in greatest dimension with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of ovarian, fallopian tube, or primary peritoneal carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Ovarian, fallopian tube, or primary peritoneal carcinoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with no regional lymph node metastasis. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with isolated tumor cells in regional lymph node(s) no greater than 0.2 mm. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with positive retroperitoneal lymph nodes only (histologically confirmed). (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with metastasis up to 10 mm in greatest dimension. (from AJCC 8th Ed.)
Ovarian, fallopian tube, or primary peritoneal carcinoma with metastasis more than 10 mm in greatest dimension. (from AJCC 8th Ed.)
A term that refers to the staging of ovarian cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to ovarian carcinomas. Nonepithelial primary ovarian cancers may be staged using this classification but should be reported separately. (from AJCC 8th Ed.)
Stage IIIA1 includes: T1/2, N1, M0. T1: Ovarian cancer with tumor limited to ovaries (one or both). T2: Ovarian cancer with tumor involving one or both ovaries with pelvic extension below pelvic brim. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA2 includes: T3a, N0/N1, M0. T3a: Ovarian cancer with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IVA includes: Any T, Any N, M1a. M1a: Ovarian cancer with pleural effusion with positive cytology. (from AJCC 8th Ed.)
Stage IVB includes: Any T, Any N, M1b. M1b: Ovarian cancer with liver or splenic parenchymal metastases; metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside the abdominal cavity); transmural involvement of intestine. (from AJCC 8th Ed.)
A stage term that applies to ovarian and fallopian tube carcinoma and indicates that the tumor is limited to ovaries (one or both) or fallopian tube(s) or the tumor involves one or both ovaries or fallopian tubes with pelvic extension below pelvic brim. There are positive retroperitoneal lymph nodes only (histologically confirmed) and no distant metastasis. (adapted from AJCC 8th Ed.)
A stage term that applies to ovarian and fallopian tube carcinoma and indicates the presence of microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. There is no distant metastasis. (adapted from AJCC 8th Ed.)
A term that refers to the staging of fallopian tube cancer according to the American Joint Committee on Cancer, 8th edition.
Stage IIIA1 includes: T1/2, N1, M0. T1: T1: Fallopian tube cancer with tumor limited to fallopian tube(s). T2: Fallopian tube cancer with tumor involving fallopian tubes with pelvic extension below pelvic brim. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIIA2 includes: T3a, N0/N1, M0. T3a: T3a: Fallopian tube cancer with microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. N0: No regional lymph node metastasis. N1: Positive retroperitoneal lymph nodes only (histologically confirmed). M0: No distant metastasis. (AJCC 8th Ed.)
Stage IVA includes: Any T, Any N, M1a. M1a: Fallopian tube cancer with pleural effusion with positive cytology. (from AJCC 8th Ed.)
Stage IVB includes: Any T, Any N, M1b. M1b: Fallopian tube cancer with liver or splenic parenchymal metastases; metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside the abdominal cavity); transmural involvement of intestine. (from AJCC 8th Ed.)
A term that refers to the staging of primary peritoneal cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of primary peritoneal cancer according to the American Joint Committee on Cancer, 8th edition.
Stage II includes: T2, N0, M0. T2: Primary peritoneal cancer. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIA includes: T2a, N0, M0. T2a: Primary peritoneal cancer with extension and/or implants on the uterus and/or fallopian tube(s) and/or ovaries. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IIB includes: T2b, N0, M0. T2b: Primary peritoneal cancer with tumor extension to and/or implants on other pelvic tissues. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage IVA includes: Any T, Any N, M1a. M1a: Primary peritoneal cancer with pleural effusion with positive cytology. (from AJCC 8th Ed.)
Stage IVB includes: Any T, Any N, M1b. M1b: Primary peritoneal cancer with liver or splenic parenchymal metastases; metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside the abdominal cavity); transmural involvement of intestine. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of a gestational trophoblastic neoplasm, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of a gestational trophoblastic neoplasm, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Gestational trophoblastic neoplasm without evidence of distant metastasis. (from AJCC 8th Ed.)
Gestational trophoblastic neoplasm with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of a gestational trophoblastic neoplasm, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of a gestational trophoblastic neoplasm, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of a gestational trophoblastic neoplasm, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Gestational trophoblastic neoplasm in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Gestational trophoblastic neoplasm with no evidence of primary tumor. (from AJCC 8th Ed.)
Gestational trophoblastic neoplasm in which the tumor is confined to uterus. (from AJCC 8th Ed.)
Gestational trophoblastic neoplasm in which the tumor extends to other genital structures (ovary, tube, vagina, broad ligaments) by metastasis or direct extension. (from AJCC 8th Ed.)
A term that refers to the staging of gestational trophoblastic tumor according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of a gestational trophoblastic neoplasm of the placenta according to the American Joint Committee on Cancer, 8th edition. This classification applies to the following placental neoplasms: invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Complete and partial hydatidiform tumors are not included in this classification. The current FIGO classification includes an anatomic stage designated by Roman numeral I, II, III, or IV, followed by the risk factor score expressed in Arabic numerals (e.g., Stage II: 4, Stage IV: 9). (from AJCC 8th Ed.)
Stage I includes: T1, M0. T1: Gestational trophoblastic neoplasm in which the tumor is confined to uterus. M0: No distant metastasis. (AJCC 8th Ed.)
Stage II includes: T2, M0. T2: Gestational trophoblastic neoplasm in which the tumor extends to other genital structures (ovary, tube, vagina, broad ligaments) by metastasis or direct extension. M0: No distant metastasis. (AJCC 8th Ed.)
Stage III includes: Any T, M1a. M1a: Gestational trophoblastic neoplasm with lung metastasis. (AJCC 8th Ed.)
Stage IV includes: Any T, M1b. M1b: Gestational trophoblastic neoplasm with all other distant metastases. (AJCC 8th Ed.)
An antagonistic agent targeting the co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT; T-cell immunoreceptor with Ig and ITIM domains; T-cell immunoglobulin and ITIM domain), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, MK-7684 targets and binds to TIGIT expressed on various immune cells, particularly on tumor-infiltrating T-lymphocytes (TILs) and natural killer (NK) cells, thereby preventing the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like protein 5; NECL-5), which are expressed on T-cells, NK cells and certain cancer cells. This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as NK cells and CD8+ T-cells, and activates CD226-mediated signaling. This activates the immune system to exert a T-cell-mediated immune response against cancer cells. TIGIT, a member of the Ig super family and an immune inhibitory receptor, is overexpressed on tumor antigen-specific CD8+ T-cells and CD8+ TILs and plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion, and the inhibition of antiviral immune responses.
A finding about one or more characteristics of male reproductive system cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to penile cancer, prostate cancer, and testicular cancer.
A finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to penile squamous cell carcinoma and associated histologic subtypes. It does not apply to urethral carcinomas, sarcomas, and melanomas. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Penile cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Penile cancer with distant metastasis present. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Penile cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Penile cancer with no palpable or visibly enlarged inguinal lymph nodes. (from AJCC 8th Ed.)
Penile cancer with palpable mobile unilateral inguinal lymph node. (from AJCC 8th Ed.)
Penile cancer with palpable mobile two or more unilateral inguinal nodes or bilateral inguinal lymph nodes. (from AJCC 8th Ed.)
Penile cancer with palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Penile cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Penile cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Penile cancer with a finding of carcinoma in situ (penile intraepithelial neoplasia [PeIN]). (from AJCC 8th Ed.)
Penile cancer with a finding of noninvasive localized squamous cell carcinoma. (from AJCC 8th Ed.)
Glans: Penile cancer with tumor invading lamina propria. Foreskin: Penile cancer with tumor invading dermis, lamina propria, or dartos fascia. Shaft: Penile cancer with tumor invading connective tissue between epidermis and corpora regardless of location. All sites with or without lymphovascular invasion or perineural invasion and is or is not high grade. (from AJCC 8th Ed.)
Penile cancer with tumor without lymphovascular invasion or perineural invasion and is not high grade (i.e., grade 3 or sarcomatoid). (from AJCC 8th Ed.)
Penile cancer with tumor exhibiting lymphovascular invasion and/or perineural invasion or is high grade (i.e., grade 3 or sarcomatoid). (from AJCC 8th Ed.)
Penile cancer with tumor invading into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. (from AJCC 8th Ed.)
Penile cancer with tumor invading into corpora cavernosum (including tunica albuginea) with or without urethral invasion. (from AJCC 8th Ed.)
Penile cancer with tumor invading into adjacent structures (i.e., scrotum, prostate, pubic bone). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of penile cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Penile cancer in which lymph node metastasis cannot be established. (from AJCC 8th Ed.)
Penile cancer with no lymph node metastasis. (from AJCC 8th Ed.)
Penile cancer with two or less unilateral inguinal metastases, no extranodal extension. (from AJCC 8th Ed.)
Penile cancer with three or more unilateral inguinal metastases or bilateral metastases. (from AJCC 8th Ed.)
A term that refers to the staging of penile cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to penile squamous cell carcinoma and associated histologic subtypes. It does not apply to urethral carcinomas, sarcomas, and melanomas. (from AJCC 8th Ed.)
Stage 0is includes: Tis, N0, M0. Tis: Penile cancer with a finding of carcinoma in situ (penile intraepithelial neoplasia [PeIN]). N0: No lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage 0a includes: Ta, N0, M0. Ta: Penile cancer with a finding of noninvasive localized squamous cell carcinoma. N0: No lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: (T1b, N0, M0); (T2, N0, M0). T1b: Penile cancer with tumor exhibiting lymphovascular invasion and/or perineural invasion or is high grade (i.e., grade 3 or sarcomatoid). T2: Penile cancer with tumor invading into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. N0: No lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T3, N0, M0. T3: Penile cancer with tumor invading into corpora cavernosum (including tunica albuginea) with or without urethral invasion. N0: No lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
An indolent non-Hodgkin lymphoma which has undergone histologic transformation to an aggressive non-Hodgkin lymphoma and has become resistant to treatment.
A clinical finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Prostate cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Prostate cancer with distant metastasis. (from AJCC 8th Ed.)
Prostate cancer with metastasis to nonregional lymph node(s). (from AJCC 8th Ed.)
Prostate cancer with metastasis to bone(s). (from AJCC 8th Ed.)
Prostate cancer with metastasis to other site(s) with or without bone disease. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Prostate cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Prostate cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Prostate cancer with clinically inapparent tumor that is not palpable. (from AJCC 8th Ed.)
Prostate cancer in which the tumor is an incidental histologic finding in 5% or less of tissue resected. (from AJCC 8th Ed.)
Prostate cancer in which the tumor is an incidental histologic finding in more than 5% of tissue resected. (from AJCC 8th Ed.)
Prostate cancer in which the tumor is identified by needle biopsy found in one or both sides, but not palpable. (from AJCC 8th Ed.)
Prostate cancer in which the tumor is palpable and confined within the prostate. (from AJCC 8th Ed.)
Prostate cancer in which the tumor involves one-half of one side or less. (from AJCC 8th Ed.)
Prostate cancer in which the tumor involves more than one-half of one side but not both sides. (from AJCC 8th Ed.)
Prostate cancer with extraprostatic tumor that is not fixed or does not invade adjacent structures. (from AJCC 8th Ed.)
Prostate cancer with extraprostatic extension (unilateral or bilateral). (from AJCC 8th Ed.)
Prostate cancer in which the tumor invades seminal vesicle(s). (from AJCC 8th Ed.)
Prostate cancer in which the tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. There is no pathologic T1 classification.
Prostate cancer which is organ confined. (from AJCC 8th Ed.)
Prostate cancer with extraprostatic extension. (from AJCC 8th Ed.)
Prostate cancer with extraprostatic extension (unilateral or bilateral) or microscopic invasion of bladder neck. (from AJCC 8th Ed.)
Prostate cancer with tumor invading seminal vesicle(s). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Prostate cancer in which the regional nodes were not assessed. (from AJCC 8th Ed.)
Prostate cancer with no positive regional nodes. (from AJCC 8th Ed.)
Prostate cancer with metastases in regional node(s). (from AJCC 8th Ed.)
An mRNA-based individualized, therapeutic cancer vaccine targeting an unspecified amount of tumor-associated antigens (TAAs) that are specifically expressed in the patient's cancer, with potential immunostimulatory and antineoplastic activities. Upon administration, the personalized cancer vaccine RO7198457 is taken up and translated by antigen presenting cells (APCs) and the expressed protein is presented via major histocompatibility complex (MHC) molecules on the surface of the APCs. This leads to an induction of both cytotoxic T-lymphocyte (CTL)- and memory T-cell-dependent immune responses against cancer cells expressing the TAA(s).
A term that refers to the staging of prostate cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to adenocarcinomas and squamous cell carcinomas of the prostate gland. It does not apply to sarcomas, urothelial cell carcinomas, and urothelial carcinoma of bladder involving prostate. (from AJCC 8th Ed.)
Stage IIC includes: (T1-2, N0, M0, PSA less than 20, Grade Group 3); (T1-2, N0, M0, PSA less than 20, Grade Group 4). T1: Prostate cancer with clinically inapparent tumor that is not palpable. T2: Prostate cancer in which the tumor is palpable and confined within the prostate. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 3: Gleason Score 7, Gleason Pattern 4+3. Grade Group 4: Gleason Score 8, Gleason Pattern 4+4. (AJCC 8th ed.)
Stage IIIA includes: T1-2, N0, M0, PSA 20 or more, Grade Group 1-4; T1: Prostate cancer with clinically inapparent tumor that is not palpable. T2: Prostate cancer in which the tumor is palpable and confined within the prostate. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 1: Gleason Score 6 or less, Gleason Pattern 3 or less+3. Grade Group 2: Gleason Score 7, Gleason Pattern 3+4. Grade Group 3: Gleason Score 7, Gleason Pattern 4+3. Grade Group 4: Gleason Score 8, Gleason Pattern 4+4. (AJCC 8th ed.)
Stage IIIB includes: T3-4, N0, M0, PSA: Any, Grade Group 1-4; T3: Prostate cancer with extraprostatic tumor that is not fixed or does not invade adjacent structures. T4: Prostate cancer in which the tumor is fixed or invades adjacent structures other than seminal vesicles such as external sphincter, rectum, bladder, levator muscles, and/or pelvic wall. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 1: Gleason Score 6 or less, Gleason Pattern 3 or less+3. Grade Group 2: Gleason Score 7, Gleason Pattern 3+4. Grade Group 3: Gleason Score 7, Gleason Pattern 4+3. Grade Group 4: Gleason Score 8, Gleason Pattern 4+4. (AJCC 8th ed.)
Stage IIIC includes: Any T, N0, M0, PSA: Any, Grade Group 5. N0: Prostate cancer with no positive regional nodes. M0: Prostate cancer without evidence of distant metastasis. Grade Group 5: Gleason Score 9 or 10, Gleason Pattern 4+5, or 5+4, or 5+5. (AJCC 8th ed.)
Stage IVA includes: Any T, N1, M0, PSA: Any, Grade Group: Any. N1: Prostate cancer with metastases in regional node(s). M0: Prostate cancer without evidence of distant metastasis. (AJCC 8th ed.)
Chronic pain following mastectomy or lumpectomy that usually affects the anterior thorax, axilla, and/or medial upper arm.
A finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to postpubertal germ cell tumors of the testis and malignant sex cord-stromal tumors of the testis. It does not apply to spermatocytic tumors (no AJCC staging system), nonmalignant sex cord-/gonadal -stromal tumors (no AJCC staging system), prepubertal germ cell tumors (no AJCC staging system), hematolymphoid tumors (hematologic malignancies staging system), and paratesticular neoplasms (no AJCC staging system). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Testicular cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Testicular cancer with distant metastasis. (from AJCC 8th Ed.)
Testicular cancer with non-retroperitoneal nodal or pulmonary metastases. (from AJCC 8th Ed.)
Testicular cancer with non-pulmonary visceral metastases. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Testicular cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Testicular cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Testicular cancer with a finding of germ cell neoplasia in situ. (from AJCC 8th Ed.)
Testicular cancer in which the tumor invades scrotum with or without vascular/lymphatic invasion. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Testicular cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Testicular cancer with no regional lymph node metastasis. (from AJCC 8th Ed.)
Testicular cancer with metastases in a lymph node mass 2 cm or smaller in greatest dimension or multiple lymph nodes, none larger than 2 cm in greatest dimension. (from AJCC 8th Ed.)
Testicular cancer with metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension or multiple lymph nodes, any one mass larger than 2 cm but not larger than 5 cm in greatest dimension. (from AJCC 8th Ed.)
Testicular cancer with metastasis with a lymph node mass larger than 5 cm in greatest dimensi. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Testicular cancer which is limited to testis (including rete testis invasion) without lymphovascular invasion. (from AJCC 8th Ed.)
Testicular cancer which is limited to testis (including rete testis invasion) without lymphovascular invasion and is smaller than 3 cm in size. This pT1 subclassification applies only to pure seminomas. (from AJCC 8th Ed.)
Testicular cancer which is limited to testis (including rete testis invasion) without lymphovascular invasion and is 3 cm or larger in size. This pT1 subclassification applies only to pure seminomas. (from AJCC 8th Ed.)
Testicular cancer which is limited to testis (including rete testis invasion) with lymphovascular invasion or invades hilar soft tissue or epididymis or penetrates visceral mesothelial layer covering the external surface of tunica albuginea with or without lymphovascular invasion. (from AJCC 8th Ed.)
Testicular cancer in which the tumor invades spermatic cord with or without lymphovascular invasion. (from AJCC 8th Ed.)
Testicular cancer in which the tumor invades scrotum with or without lymphovascular invasion. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of testicular cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Testicular cancer with metastasis with a lymph node mass 2 cm or smaller in greatest dimension and less than or equal to five nodes positive, none larger than 2 cm in greatest dimension. (from AJCC 8th Ed.)
Testicular cancer with metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension; or more than five nodes positive, none larger than 5 cm; or evidence of extranodal extension of tumor. (from AJCC 8th Ed.)
Testicular cancer with metastasis with a lymph node mass larger than 5 cm in greatest dimension. (from AJCC 8th Ed.)
A term that refers to the staging of testicular cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to postpubertal germ cell tumors of the testis and malignant sex cord-stromal tumors of the testis. It does not apply to spermatocytic tumors (no AJCC staging system), nonmalignant sex cord-/gonadal -stromal tumors (no AJCC staging system), prepubertal germ cell tumors (no AJCC staging system), hematolymphoid tumors (hematologic malignancies staging system), and paratesticular neoplasms (no AJCC staging system). (from AJCC 8th Ed.)
Stage 0 includes: pTis, N0, M0, S0. pTis: Testicular cancer with a finding of germ cell neoplasia in situ. N0: Testicular cancer with no regional lymph node metastasis. M0: Testicular cancer without evidence of distant metastasis. S0: Marker study levels within normal limits. (AJCC 8th ed.)
Stage I includes: pT1-T4, N0, M0, SX. pT1: Testicular cancer which is limited to testis (including rete testis invasion) without lymphovascular invasion. pT2: Testicular cancer which is limited to testis (including rete testis invasion) with lymphovascular invasion or invades hilar soft tissue or epididymis or penetrates visceral mesothelial layer covering the external surface of tunica albuginea with or without lymphovascular invasion. pT3: Testicular cancer in which the tumor invades spermatic cord with or without lymphovascular invasion. pT4: Testicular cancer in which the tumor invades scrotum with or without lymphovascular invasion. N0: Testicular cancer with no regional lymph node metastasis. M0: Testicular cancer without evidence of distant metastasis. SX: Marker studies not available or not performed. (AJCC 8th ed.)
Stage IA includes: pT1, N0, M0, S0. pT1: Testicular cancer which is limited to testis (including rete testis invasion) without lymphovascular invasion. N0: Testicular cancer with no regional lymph node metastasis. M0: Testicular cancer without evidence of distant metastasis. S0: Marker study levels within normal limits. (AJCC 8th ed.)
Stage IB includes: (pT2, N0, M0, S0); (pT3, N0, M0, S0); (pT4, N0, M0, S0). pT2: Testicular cancer which is limited to testis (including rete testis invasion) with lymphovascular invasion or invades hilar soft tissue or epididymis or penetrates visceral mesothelial layer covering the external surface of tunica albuginea with or without lymphovascular invasion. pT3: Testicular cancer in which the tumor invades spermatic cord with or without lymphovascular invasion. pT4: Testicular cancer in which the tumor invades scrotum with or without lymphovascular invasion. N0: Testicular cancer with no regional lymph node metastasis. M0: Testicular cancer without evidence of distant metastasis. S0: Marker study levels within normal limits. (AJCC 8th ed.)
Stage IS includes: Any pT/TX, N0, M0, S1-3. TX: Testicular cancer in which the primary tumor cannot be assessed. N0: Testicular cancer with no regional lymph node metastasis. M0: Testicular cancer without evidence of distant metastasis. S1: LDH less than 1.5 x N and hCG (mlU/mL) less than 5,000 and AFP (ng/mL) less than 1,000. S2: LDH 1.5-10 x N or hCG (mlU/mL) 5,000-50,000 or AFP (ng/mL) 1,000-10,000. S3: LDH more than 10 x N or hCG (mlU/mL) more than 50,000 or AFP (ng/mL) more than 10,000. N indicates the upper limit of normal for the LDH assay. (AJCC 8th ed.)
Stage II includes: Any pT/TX, N1-3, M0, SX. TX: Testicular cancer in which the primary tumor cannot be assessed. N1: Testicular cancer with metastasis with a lymph node mass 2 cm or smaller in greatest dimension and less than or equal to five nodes positive, none larger than 2 cm in greatest dimension. N2: Testicular cancer with metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension; or more than five nodes positive, none larger than 5 cm; or evidence of extranodal extension of tumor. N3: Testicular cancer with metastasis with a lymph node mass larger than 5 cm in greatest dimension. M0: Testicular cancer without evidence of distant metastasis. SX: Marker studies not available or not performed. (AJCC 8th ed.)
Stage IIA includes: (Any pT/TX, N1, M0, S0); (Any pT/TX, N1, M0, S1). TX: Testicular cancer in which the primary tumor cannot be assessed. N1: Testicular cancer with metastasis with a lymph node mass 2 cm or smaller in greatest dimension and less than or equal to five nodes positive, none larger than 2 cm in greatest dimension. M0: Testicular cancer without evidence of distant metastasis. S0: Marker study levels within normal limits. S1: LDH less than 1.5 x N and hCG (mlU/mL) less than 5,000 and AFP (ng/mL) less than 1,000. N indicates the upper limit of normal for the LDH assay. (AJCC 8th ed.)
Stage IIB includes: (Any pT/TX, N2, M0, S0); (Any pT/TX, N2, M0, S1). TX: Testicular cancer in which the primary tumor cannot be assessed. N2: Testicular cancer with metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension; or more than five nodes positive, none larger than 5 cm; or evidence of extranodal extension of tumor. M0: Testicular cancer without evidence of distant metastasis. S0: Marker study levels within normal limits. S1: LDH less than 1.5 x N and hCG (mlU/mL) less than 5,000 and AFP (ng/mL) less than 1,000. N indicates the upper limit of normal for the LDH assay. (AJCC 8th ed.)
Stage III includes: Any pT/TX, Any N, M1, SX. TX: Testicular cancer in which the primary tumor cannot be assessed. M1: Testicular cancer with distant metastasis. SX: Marker studies not available or not performed. (AJCC 8th ed.)
Stage IIIA includes: (Any pT/TX, Any N, M1a, S0); (Any pT/TX, Any N, M1a, S1). TX: Testicular cancer in which the primary tumor cannot be assessed. M1a: Testicular cancer with non-retroperitoneal nodal or pulmonary metastases. S0: Marker study levels within normal limits. S1: LDH less than 1.5 x N and hCG (mlU/mL) less than 5,000 and AFP (ng/mL) less than 1,000. N indicates the upper limit of normal for the LDH assay. (AJCC 8th ed.)
Stage IIIB includes: (Any pT/TX, N1-3, M0, S2); (Any pT/TX, Any N, M1a, S2). TX: Testicular cancer in which the primary tumor cannot be assessed. N1: Testicular cancer with metastasis with a lymph node mass 2 cm or smaller in greatest dimension and less than or equal to five nodes positive, none larger than 2 cm in greatest dimension. N2: Testicular cancer with metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension; or more than five nodes positive, none larger than 5 cm; or evidence of extranodal extension of tumor. N3: Testicular cancer with metastasis with a lymph node mass larger than 5 cm in greatest dimension. M0: Testicular cancer without evidence of distant metastasis. M1a: Testicular cancer with non-retroperitoneal nodal or pulmonary metastases. S2: LDH 1.5-10 x N or hCG (mlU/mL) 5,000-50,000 or AFP (ng/mL) 1,000-10,000. N indicates the upper limit of normal for the LDH assay. (AJCC 8th ed.)
Stage IIIC includes: (Any pT/TX, N1-3, M0, S3); (Any pT/TX, Any N, M1a, S3); (Any pT/TX, Any N, M1b, Any S). TX: Testicular cancer in which the primary tumor cannot be assessed. N1: Testicular cancer with metastasis with a lymph node mass 2 cm or smaller in greatest dimension and less than or equal to five nodes positive, none larger than 2 cm in greatest dimension. N2: Testicular cancer with metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension; or more than five nodes positive, none larger than 5 cm; or evidence of extranodal extension of tumor. N3: Testicular cancer with metastasis with a lymph node mass larger than 5 cm in greatest dimension. M0: Testicular cancer without evidence of distant metastasis. M1a: Testicular cancer with non-retroperitoneal nodal or pulmonary metastases. M1b: Testicular cancer with non-pulmonary visceral metastases. S3: LDH more than 10 x N or hCG (mlU/mL) more than 50,000 or AFP (ng/mL) more than 10,000. N indicates the upper limit of normal for the LDH assay. (AJCC 8th ed.)
A term that refers to the staging of testicular cancer according to the American Joint Committee on Cancer, 6th and 7th editions.
A nucleotide substitution at position 35 of the coding sequence of the NRAS gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 12 in the GTPase NRas protein where glycine has been replaced by valine.
A nucleotide substitution at position 35 of the coding sequence of the HRAS gene where guanine has been mutated to thymine.
A variation in the amino acid sequence for the GTPase HRas protein.
A complex substitution where the nucleotide sequence at positions 35 and 36 of the coding sequence of the HRAS gene has changed from guanine-cytosine to thymine-adenine.
A change in the amino acid residue at position 12 in the GTPase HRas protein where glycine has been replaced by valine.
Macular dystrophy that is related to a change in a gene.
A finding about one or more characteristics of urinary tract cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to carcinomas arising in the kidney. It does not apply to urothelial carcinomas (are staged according to the classification for renal pelvis and ureter), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), sarcomas (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs), and Wilms tumor (no AJCC staging system). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Kidney cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Kidney cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Kidney cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Kidney cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Kidney cancer in which the tumor measures 4 cm or less in greatest dimension and is limited to the kidney. (from AJCC 8th Ed.)
Kidney cancer in which the tumor measures more than 4 cm but 7 cm or less in greatest dimension and is limited to the kidney. (from AJCC 8th Ed.)
Kidney cancer in which the tumor measures more than 7 cm in greatest dimension and is limited to the kidney. (from AJCC 8th Ed.)
Kidney cancer in which the tumor measures more than 7 cm but 10 cm or less in greatest dimension and is limited to the kidney. (from AJCC 8th Ed.)
Kidney cancer in which the tumor measures more than 10 cm in greatest dimension and is limited to the kidney. (from AJCC 8th Ed.)
Kidney cancer in which the tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota's fascia. (from AJCC 8th Ed.)
Kidney cancer in which the tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perirenal and/or renal sinus fat but not beyond Gerota's fascia. (from AJCC 8th Ed.)
Kidney cancer in which the tumor extends into the vena cava below the diaphragm. (from AJCC 8th Ed.)
Kidney cancer in which the tumor extends into the vena cava above the diaphragm or invades the wall of the vena cava. (from AJCC 8th Ed.)
Kidney cancer in which the tumor invades beyond Gerota's fascia (including contiguous extension into the ipsilateral adrenal gland). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of kidney cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Kidney cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Kidney cancer with no regional lymph node metastasis. (from AJCC 8th Ed.)
Kidney cancer with metastasis in regional lymph node(s). (from AJCC 8th Ed.)
A term that refers to the staging of kidney cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to carcinomas arising in the kidney. It does not apply to urothelial carcinomas (are staged according to the classification for renal pelvis and ureter), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), sarcomas (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs), and Wilms tumor (no AJCC staging system). (from AJCC 8th Ed.)
A nonfunctional well differentiated neuroendocrine neoplasm that has spread to other anatomic sites or no longer responds to treatment.
A nonfunctional well differentiated neuroendocrine neoplasm that has spread from the original site of growth to another anatomic site.
A semi-quantitative microscopic finding indicating that 25 percent or more of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A clinical finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Renal pelvis and ureter cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Renal pelvis and ureter cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer with a finding of papillary noninvasive carcinoma. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer in which the tumor invades subepithelial connective tissue. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer in which the tumor invades the muscularis. (from AJCC 8th Ed.)
For renal pelvis only: Tumor invades beyond muscularis into peripelvic fat or into the renal parenchyma. For ureter only: Tumor invades beyond muscularis into periureteric fat. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer in which the tumor invades adjacent organs, or through the kidney into the perinephric fat. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Renal pelvis and ureter cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer with no regional lymph node metastasis. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer with metastasis in a single lymph node, 2 cm or less in greatest dimension. (from AJCC 8th Ed.)
Renal pelvis and ureter cancer with metastasis in a single lymph node, more than 2 cm in greatest dimension; or multiple lymph nodes. (from AJCC 8th Ed.)
An orally available, nonsteroidal selective estrogen receptor degrader/downregulator (SERD), with potential antineoplastic activity. Upon oral administration, SERD SAR439859 specifically targets and binds to the estrogen receptor (ER) and induces a conformational change that promotes ER degradation. This prevents ER-mediated signaling and inhibits both the growth and survival of ER-expressing cancer cells.
A term that refers to the staging of renal pelvis and ureter cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to renal pelvis and ureter urothelial (transitional cell) carcinoma, including histologic variants micropapillary and nested subtypes. It does not apply to renal cell carcinomas (are staged according to the classification for kidney), renal medullary carcinomas (are staged according to the classification for kidney), collecting duct carcinomas (are staged according to the classification for kidney), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), and mesenchymal tumors (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs). (from AJCC 8th Ed.)
A term that refers to the staging of renal pelvis cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to renal pelvis urothelial (transitional cell) carcinoma, including histologic variants micropapillary and nested subtypes. It does not apply to renal cell carcinomas (are staged according to the classification for kidney), renal medullary carcinomas (are staged according to the classification for kidney), collecting duct carcinomas (are staged according to the classification for kidney), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), and mesenchymal tumors (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs). (from AJCC 8th Ed.)
A term that refers to the staging of ureter cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to ureter urothelial (transitional cell) carcinoma, including histologic variants micropapillary and nested subtypes. (from AJCC 8th Ed.)
A term that refers to the staging of renal pelvis and ureter cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of renal pelvis cancer according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of ureter cancer according to the American Joint Committee on Cancer, 7th edition.
An orally bioavailable, selective pan-tropomyosin-related-kinase (tyrosine receptor kinase; TRK) inhibitor, with potential antineoplastic activity. Upon oral administration, ONO-7579 specifically targets and binds to TRK and fusion proteins containing sequences from neurotrophic tyrosine receptor kinase (NTRK) types 1 (NTRK1; TrkA), 2 (NTRK2; TrkB), and 3 (NTRK3; TrkC). This inhibits neurotrophin-TRK interaction and TRK activation, thereby preventing the activation of downstream signaling pathways and resulting in both the induction of cellular apoptosis and the inhibition of cell growth in tumors that overexpress TRK and/or express NTRK fusion proteins. TRK, a family of receptor tyrosine kinases (RTKs) activated by neurotrophins, is encoded by NTRK family genes.The expression of either mutated forms of, or fusion proteins involving, NTRK family members results in uncontrolled TRK signaling, which plays an important role in tumor cell growth, survival, invasion and treatment resistance.
A finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to carcinomas arising in the bladder. The typical carcinoma of the bladder is urothelial carcinoma. These carcinomas may include other histologic elements, including adenocarcinoma, squamous cell carcinoma, and small cell neuroendocrine carcinoma, but should be classified as urothelial unless the cancer is composed entirely of the alternative histology. All histologic cell types that are derived primarily from the urinary bladder epithelium should follow this classification system. It does not apply to prostatic urothelial carcinomas (are staged according to the classification for urethra), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), and sarcomas (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Bladder cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Bladder cancer with distant metastasis. (from AJCC 8th Ed.)
Bladder cancer with distant metastasis limited to lymph nodes beyond the common iliacs. (from AJCC 8th Ed.)
Bladder cancer with non-lymph node distant metastases. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Bladder cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Bladder cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Bladder cancer with a finding of non-invasive papillary carcinoma. (from AJCC 8th Ed.)
Bladder cancer with a finding of urothelial carcinoma in situ: ""flat tumor"". (from AJCC 8th Ed.)
Bladder cancer with tumor invading lamina propria (subepithelial connective tissue). (from AJCC 8th Ed.)
Bladder cancer with tumor invading muscularis propria. (from AJCC 8th Ed.)
Bladder cancer with tumor invading superficial muscularis propria (inner half). (from AJCC 8th Ed.)
Bladder cancer with tumor invading deep muscularis propria (outer half). (from AJCC 8th Ed.)
Bladder cancer with tumor invading perivesical soft tissue. (from AJCC 8th Ed.)
Bladder cancer with tumor invading perivesical soft tissue, microscopically. (from AJCC 8th Ed.)
Bladder cancer with extravesical tumor directly invading any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall. (from AJCC 8th Ed.)
Bladder cancer with extravesical tumor invading directly into prostatic stroma, uterus, vagina. (from AJCC 8th Ed.)
Bladder cancer with extravesical tumor invading pelvic wall, abdominal wall. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of bladder cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Bladder cancer in which the lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Bladder cancer with no lymph node metastasis. (from AJCC 8th Ed.)
Bladder cancer with single regional lymph node metastasis in the true pelvis (perivesical, obturator, internal and external iliac, or sacral lymph node). (from AJCC 8th Ed.)
Bladder cancer with multiple regional lymph node metastasis in the true pelvis (perivesical, obturator, internal and external iliac, or sacral lymph node metastasis). (from AJCC 8th Ed.)
Bladder cancer with lymph node metastasis to the common iliac lymph nodes. (from AJCC 8th Ed.)
A change in the amino acid residue at position 172 in the isocitrate dehydrogenase [NADP], mitochondrial protein where arginine has been replaced by tryptophan.
A nucleotide substitution at position 514 of the coding sequence of the IDH2 gene where adenine has been mutated to thymine.
A term that refers to the staging of bladder cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to carcinomas arising in the bladder. The typical carcinoma of the bladder is urothelial carcinoma. These carcinomas may include other histologic elements, including adenocarcinoma, squamous cell carcinoma, and small cell neuroendocrine carcinoma, but should be classified as urothelial unless the cancer is composed entirely of the alternative histology. All histologic cell types that are derived primarily from the urinary bladder epithelium should follow this staging system. It does not apply to prostatic urothelial carcinomas (are staged according to the classification for urethra), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), and sarcomas (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs). (from AJCC 8th Ed.)
Stage IIIB includes: T1-T4a, N2, N3, M0. T1: Tumor invades lamina propria (subepithelial connective tissue). T2: Tumor invades muscularis propria. T3: Tumor invades perivesical soft tissue. T4a: Extravesical tumor invades directly into prostatic stroma, uterus, vagina. N2: Multiple regional lymph node metastasis in the true pelvis (perivesical, obturator, internal and external iliac, or sacral lymph node metastasis). N3: Lymph node metastasis to the common iliac lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
A proprietary preparation composed of an immunoglobulin G4 (IgG4) directed against the cell surface glycoprotein CD-38 (CD38) that is fused to an attenuated form of human interferon alpha (IFN alpha; IFNa), with potential immunomodulating and antineoplastic activities. Upon administration, the IgG4 moiety of the anti-CD38-targeted IgG4-attenuated IFNa TAK-573 specifically targets and binds to CD38 on CD38-positive tumor cells. In turn, the IFNa moiety binds to cell-surface IFN receptors, and activates IFN-mediated signal transduction pathways, which results in the transcription and translation of genes whose products may cause antiproliferative effects in CD38-positive tumor cells. CD38, a type II transmembrane glycoprotein, is present on various immune cells and hematologic malignancies, and its expression has been correlated with poor prognosis.
A finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to urothelial (transitional cell), squamous, and glandular carcinomas of the urethra and to urothelial (transitional cell) carcinomas of the prostate and prostatic urethra. It does not apply to squamous cell carcinomas of the penile foreskin (are staged according to the classification for penis), primary urothelial carcinomas of the bladder with transmural involvement of the prostate (are staged according to the classification for urinary bladder), prostatic adenocarcinomas (are staged according to the classification for prostate), mucosal melanomas of the urethra (no AJCC staging system), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), and sarcomas (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Urethral cancer without evidence of distant metastasis. (from AJCC 8th Ed.)
Urethral cancer with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
A pathologic finding about one or more characteristics of cancer in the male penile urethra and female urethra, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Urethral cancer in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Urethral cancer with no evidence of primary tumor. (from AJCC 8th Ed.)
Urethral cancer with a finding of non-invasive papillary carcinoma. (from AJCC 8th Ed.)
Urethral cancer with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Urethral cancer with tumor invading subepithelial connective tissue. (from AJCC 8th Ed.)
Urethral cancer with tumor invading any of the following: corpus spongiosum, periurethral muscle. (from AJCC 8th Ed.)
Urethral cancer with tumor invading any of the following: corpus cavernosum, anterior vagina. (from AJCC 8th Ed.)
Urethral cancer with tumor invading other adjacent organs (e.g., invasion of the bladder wall). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of cancer in the prostatic urethra, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Urethral cancer with a finding of carcinoma in situ involving the prostatic urethra or periurethral or prostatic ducts without stromal invasion. (from AJCC 8th Ed.)
Urethral cancer with tumor invading urethral subepithelial connective tissue immediately underlying the urothelium. (from AJCC 8th Ed.)
Urethral cancer with tumor invading the prostatic stroma surrounding ducts either by direct extension from the urothelial surface or by invasion from prostatic ducts. (from AJCC 8th Ed.)
Urethral cancer with tumor invading the periprostatic fat. (from AJCC 8th Ed.)
Urethral cancer with tumor invading other adjacent organs (e.g., extraprostatic invasion of the bladder wall, rectal wall). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of urethral cancer, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Urethral cancer in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Urethral cancer with no regional lymph node metastasis. (from AJCC 8th Ed.)
Urethral cancer with single regional lymph node metastasis in the inguinal region or true pelvis [perivesical, obturator, internal (hypogastric) and external iliac], or presacral lymph node. (from AJCC 8th Ed.)
A term that refers to the staging of urethral cancer according to the American Joint Committee on Cancer, 8th edition. This staging system applies to urothelial (transitional cell), squamous, and glandular carcinomas of the urethra and to urothelial (transitional cell) carcinomas of the prostate and prostatic urethra. It does not apply to squamous cell carcinomas of the penile foreskin (are staged according to the classification for penis), primary urothelial carcinomas of the bladder with transmural involvement of the prostate (are staged according to the classification for urinary bladder), prostatic adenocarcinomas (are staged according to the classification for prostate), mucosal melanomas of the urethra (no AJCC staging system), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), and sarcomas (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs). (from AJCC 8th Ed.)
A term that refers to the staging of urethral cancer according to the American Joint Committee on Cancer, 7th edition.
A finding about one or more characteristics of ophthalmic sites cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of eyelid carcinoma, following the rules of the TNM AJCC v8 classification system. This classification system applies to all primary carcinomas of the eyelid, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sebaceous carcinoma, and other rare carcinomas, such as all varieties of sweat gland carcinoma (e.g., eccrine carcinoma). It does not apply to carcinomas of the head and neck with direct extension to eyelid (are staged according to the cutaneous squamous cell carcinomas of the head and neck), Merkel cell carcinomas of the eyelid (are staged according to the classification for Merkel cell carcinomas), and melanomas of the eyelid (are staged according to the classification for melanomas of the skin). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of eyelid carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of eyelid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Eyelid carcinoma with no evidence of distant metastasis. (from AJCC 8th Ed.)
Eyelid carcinoma with distant metastasis. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of eyelid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Eyelid carcinoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Eyelid carcinoma with no evidence of lymph node involvement. (from AJCC 8th Ed.)
Eyelid carcinoma with metastasis in a single ipsilateral regional lymph node, measuring 3 cm or less in greatest dimension. (from AJCC 8th Ed.)
Eyelid carcinoma with metastasis in a single ipsilateral regional lymph node, measuring 3 cm or less in greatest dimension based on clinical evaluation or imaging findings. (from AJCC 8th Ed.)
Eyelid carcinoma with metastasis in a single ipsilateral regional lymph node, measuring more than 3 cm in greatest dimension, or in bilateral or contralateral lymph nodes. (from AJCC 8th Ed.)
Eyelid carcinoma with metastasis in a single ipsilateral regional lymph node, measuring more than 3 cm in greatest dimension, or in bilateral or contralateral lymph nodes documented based on clinical evaluation or imaging findings. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of eyelid carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of eyelid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of eyelid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Eyelid carcinoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Eyelid carcinoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Eyelid carcinoma with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring 10 mm or less in greatest dimension. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring 10 mm or less in greatest dimension without invasion of the tarsal plate or eyelid margin. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring 10 mm or less in greatest dimension with invasion of the tarsal plate or eyelid margin. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring 10 mm or less in greatest dimension involving the full thickness of the eyelid. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring more than 10 mm but 20 mm or less in greatest dimension. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring more than 10 mm but 20 mm or less in greatest dimension without invasion of the tarsal plate or eyelid margin. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring more than 10 mm but 20 mm or less in greatest dimension with invasion of the tarsal plate or eyelid margin. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring more than 10 mm but 20 mm or less in greatest dimension involving the full thickness of the eyelid. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring more than 20 mm but 30 mm or less in greatest dimension. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring more than 20 mm but 30 mm or less in greatest dimension without invasion of the tarsal plate or eyelid margin. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor measuring more than 20 mm but 30 mm or less in greatest dimension with invasion of the tarsal plate or eyelid margin. (from AJCC 8th Ed.)
Any eyelid carcinoma invading adjacent ocular, orbital, or facial structures. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor invading ocular or intraorbital structures. (from AJCC 8th Ed.)
Eyelid carcinoma with tumor invading (or eroding through) the bony walls of the orbit or extending to the paranasal sinuses or invading the lacrimal sac/nasolacrimal duct or brain. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of eyelid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Eyelid carcinoma with metastasis in a single ipsilateral regional lymph node, measuring 3 cm or less in greatest dimension based on lymph node biopsy. (from AJCC 8th Ed.)
Eyelid carcinoma with metastasis in a single ipsilateral regional lymph node, measuring more than 3 cm in greatest dimension, or in bilateral or contralateral lymph nodes documented based on microscopic findings on lymph node biopsy. (from AJCC 8th Ed.)
A term that refers to the staging of eyelid carcinoma according to the American Joint Committee on Cancer, 7th edition.
A term that refers to the staging of eyelid carcinoma according to the American Joint Committee on Cancer, 8th edition. This staging system applies to all primary carcinomas of the eyelid, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), sebaceous carcinoma, and other rare carcinomas, such as all varieties of sweat gland carcinoma (e.g., eccrine carcinoma). It does not apply to carcinomas of the head and neck with direct extension to eyelid (are staged according to the cutaneous squamous cell carcinomas of the head and neck), Merkel cell carcinomas of the eyelid (are staged according to the classification for Merkel cell carcinomas), and melanomas of the eyelid (are staged according to the classification for melanomas of the skin). (from AJCC 8th Ed.)
Stage 0 includes: Tis, N0, M0. Tis: Carcinoma in situ. N0: No evidence of lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage I includes: IA: T1, N0, M0; IB: T2a, N0, M0. T1: Tumor measuring 10 mm or less in greatest dimension. T2a: Tumor measuring more than 10 mm but 20 mm or less in greatest dimension without invasion of the tarsal plate or eyelid margin. N0: No evidence of lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage IA includes: T1, N0, M0. T1: Tumor measuring 10 mm or less in greatest dimension. N0: No evidence of lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage IB includes: T2a, N0, M0. T2a: Tumor measuring more than 10 mm but 20 mm or less in greatest dimension without invasion of the tarsal plate or eyelid margin. N0: No evidence of lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA: T2b-c, T3, N0, M0; IIB: T4, N0, M0. T2b: Tumor measuring more than 10 mm but 20 mm or less in greatest dimension with invasion of the tarsal plate or eyelid margin. T2c: Tumor measuring more than 10 mm but 20 mm or less in greatest dimension involving the full thickness of the eyelid. T3: Tumor measuring more than 20 mm but 30 mm or less in greatest dimension. T4: Any eyelid carcinoma invading adjacent ocular, orbital, or facial structures. N0: No evidence of lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: T2b-c, T3, N0, M0: T2b: Tumor measuring more than 10 mm but 20 mm or less in greatest dimension with invasion of the tarsal plate or eyelid margin. T2c: Tumor measuring more than 10 mm but 20 mm or less in greatest dimension involving the full thickness of the eyelid. T3: Tumor measuring more than 20 mm but 30 mm or less in greatest dimension. N0: No evidence of lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: T4, N0, M0. T4: Any eyelid carcinoma invading adjacent ocular, orbital, or facial structures. N0: No evidence of lymph node involvement. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA: Any T, N1, M0; IIIB: Any T, N2, M0. N1: Metastasis in a single ipsilateral regional lymph node, measuring 3 cm or less in greatest dimension. N2: Metastasis in a single ipsilateral regional lymph node, measuring more than 3 cm in greatest dimension, or in bilateral or contralateral lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIA includes: Any T, N1, M0. N1: Metastasis in a single ipsilateral regional lymph node, measuring 3 cm or less in greatest dimension. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: Any T, N2, M0. N2: Metastasis in a single ipsilateral regional lymph node, measuring more than 3 cm in greatest dimension, or in bilateral or contralateral lymph nodes. M0: No distant metastasis. (AJCC 8th ed.)
A finding about one or more characteristics of conjunctival carcinoma, following the rules of the TNM AJCC v8 classification system. This classification system applies only to carcinoma of the conjunctiva. Other tumors of the conjunctiva, including secondary conjunctival tumors (e.g., intraocular tumors extending through the conjunctiva, such as uveal melanoma or uveal non-Hodgkin lymphoma, and orbital tumors extending into the conjunctiva, such as rhabdomyosarcoma), are not classified using this schema. Conjunctival lymphomas are staged according to the classification for ocular adnexal lymphoma and conjunctival melanomas are staged according to the classification for conjunctival melanoma. There is no proposal for anatomic stage and prognostic groups for conjunctival carcinoma. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of conjunctival carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of conjunctival carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Conjunctival carcinoma with no distant metastasis. (from AJCC 8th Ed.)
Conjunctival carcinoma with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of conjunctival carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of conjunctival carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of conjunctival carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Conjunctival carcinoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Conjunctival carcinoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Conjunctival carcinoma with a finding of carcinoma in situ. (from AJCC 8th Ed.)
Conjunctival carcinoma with tumor measuring 5 mm or less in greatest dimension and invading through the conjunctival basement membrane without invasion of adjacent structures. (from AJCC 8th Ed.)
Conjunctival carcinoma with tumor measuring more than 5 mm in greatest dimension and invading through the conjunctival basement membrane without invasion of adjacent structures. (from AJCC 8th Ed.)
Conjunctival carcinoma with tumor invading adjacent structures (excluding the orbit). (from AJCC 8th Ed.)
Conjunctival carcinoma with tumor invading the orbit with or without further extension. (from AJCC 8th Ed.)
Conjunctival carcinoma with tumor invading orbital soft tissues without bone invasion. (from AJCC 8th Ed.)
Conjunctival carcinoma with tumor invading bone. (from AJCC 8th Ed.)
Conjunctival carcinoma with tumor invading adjacent paranasal sinuses. (from AJCC 8th Ed.)
Conjunctival carcinoma with tumor invading brain. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of conjunctival carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Conjunctival carcinoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Conjunctival carcinoma with no regional lymph node metastasis. (from AJCC 8th Ed.)
Conjunctival carcinoma with regional lymph node metastasis. (from AJCC 8th Ed.)
An antibody-drug conjugate (ADC) consisting of an engineered version of anti-human prostate-specific membrane antigen (PSMA) monoclonal antibody J591 conjugated, via a valine-alanine dipeptide linker, to tesirine, a cytotoxic, DNA minor groove crosslinking agent and pyrrolobenzodiazepine (PBD) dimer, with potential antineoplastic activity. Upon administration of anti-PSMA/PBD ADC MEDI3726, the antibody moiety targets the cell surface antigen PSMA, which is found on prostate cancer cells. Upon antibody/antigen binding, internalization and lysosome-mediated cleavage of the dipeptide linker, the cytotoxic PBD moiety is released. In turn, the imine groups of the PBD moiety bind to the N2 positions of guanines on opposite strands of DNA. This induces DNA strand breaks, inhibits DNA replication, leads to G2/M cell cycle arrest, induces cell death, and inhibits the proliferation of PSMA-overexpressing tumor cells. PSMA is overexpressed by prostate cancers; its expression is associated with poor prognosis and metastasis.
A proprietary botanical, galactolipid-enriched extract derived from the edible plant Crassocephalum crepidioides (Zhaohe Cao), with potential anti-inflammatory and antineoplastic activities. Upon oral administration, DCB-BO1301 may inhibit the growth of certain types of tumor cells, although the exact mechanism of action has yet to be fully elucidated.
A radioconjugate composed of AC0010, an orally available, third generation, selective inhibitor of mutant forms of the epidermal growth factor receptor (EGFR), including the second-site resistance mutation T790M, that is labeled with the radioisotope carbon C 14, with potential use in evaluating the pharmacokinetic profile of AC0010. Upon administration, the AC0010 moiety specifically and irreversibly binds to and inhibits the activity of mutant forms of EGFR. Labeling of AC0010 with the radioactive tracer carbon C 14 allows for the evaluation of AC0010's pharmacokinetic profile, including its absorption, distribution, metabolism, and excretion (ADME).
A finding about one or more characteristics of conjunctival melanoma, following the rules of the TNM AJCC v8 classification system. This classification system applies to melanomas arising from the bulbar and palpebral conjunctiva and from the caruncle. Primary eyelid melanomas are staged according to the classification for melanoma of the skin and secondary involvement of the conjunctiva by extraocular uveal melanoma is staged according to the classification for uveal melanoma. There is no proposal for anatomic stage and prognostic groups for conjunctival melanoma. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of conjunctival melanoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of conjunctival melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Conjunctival melanoma with no distant metastasis. (from AJCC 8th Ed.)
Conjunctival melanoma with distant metastasis. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of conjunctival melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Conjunctival melanoma in which the primary tumor cannot be assessed. (from AJCC 8th Ed.)
Conjunctival melanoma with no evidence of primary tumor. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the bulbar conjunctiva. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the bulbar conjunctiva, involving less than 1 quadrant. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the bulbar conjunctiva, involving 1 or more to less than 2 quadrants. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the bulbar conjunctiva, involving 2 or more to less than 3 quadrants. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the bulbar conjunctiva, involving 3 or more quadrants. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the nonbulbar (forniceal, palpebral, tarsal) conjunctiva, and tumor involving the caruncle. (from AJCC 8th Ed.)
Conjunctival melanoma with noncaruncular tumor, and 1 or less quadrant of the nonbulbar conjunctiva involved. (from AJCC 8th Ed.)
Conjunctival melanoma with noncaruncular tumor, and more than 1 quadrant of the nonbulbar conjunctiva involved. (from AJCC 8th Ed.)
Conjunctival melanoma with caruncular tumor, and 1 or less quadrant of the nonbulbar conjunctiva involved. (from AJCC 8th Ed.)
Conjunctival melanoma with caruncular tumor, and more than 1 quadrant of the nonbulbar conjunctiva involved. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of any size with local invasion. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of any size invading the globe. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of any size invading the eyelid. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of any size invading the orbit. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of any size invading the nasolacrimal duct and/or lacrimal sac and/or paranasal sinuses. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of any size invading the central nervous system. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of conjunctival melanoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of conjunctival melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Conjunctival melanoma confined to the conjunctival epithelium. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the bulbar conjunctiva invading the substantia propria, not more than 2.0 mm in thickness. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the bulbar conjunctiva invading the substantia propria, more than 2.0 mm in thickness. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the nonbulbar conjunctiva with invasion of the substantia propria, not more than 2.0 mm in thickness. (from AJCC 8th Ed.)
Conjunctival melanoma with tumor of the nonbulbar conjunctiva with invasion of the substantia propria, more than 2.0 mm in thickness. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of conjunctival melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Conjunctival melanoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Conjunctival melanoma with no regional lymph node metastasis. (from AJCC 8th Ed.)
Conjunctival melanoma with regional lymph node metastasis. (from AJCC 8th Ed.)
A finding about one or more characteristics of uveal melanoma, following the rules of the TNM AJCC v8 classification system. This classification system applies to malignant melanoma of the iris, ciliary body, and choroid. Cutaneous melanoma metastatic to the iris, ciliary body, and choroid is staged according to the classification for melanoma of the skin and secondary intraocular extension of conjunctival melanoma is staged according to the classification for conjunctival melanoma. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of uveal melanoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of uveal melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Uveal melanoma with no distant metastasis by clinical classification. (from AJCC 8th Ed.)
Uveal melanoma with distant metastasis. (from AJCC 8th Ed.)
Uveal melanoma with largest diameter of the largest metastasis 3.0 cm or less. (from AJCC 8th Ed.)
Uveal melanoma with largest diameter of the largest metastasis 3.1-8.0 cm. (from AJCC 8th Ed.)
Uveal melanoma with largest diameter of the largest metastasis 8.1 cm or more. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of uveal melanoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of uveal melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of iris melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Iris melanoma with tumor limited to the iris. (from AJCC 8th Ed.)
Iris melanoma with tumor limited to the iris, not more than 3 clock hours in size. (from AJCC 8th Ed.)
Iris melanoma with tumor limited to the iris, more than 3 clock hours in size. (from AJCC 8th Ed.)
Iris melanoma with tumor limited to the iris with secondary glaucoma. (from AJCC 8th Ed.)
Iris melanoma with tumor confluent with or extending into the ciliary body, choroid, or both. (from AJCC 8th Ed.)
Iris melanoma with tumor confluent with or extending into the ciliary body and choroid, without secondary glaucoma. (from AJCC 8th Ed.)
Iris melanoma with tumor confluent with or extending into the ciliary body, choroid, or both, with secondary glaucoma. (from AJCC 8th Ed.)
Iris melanoma with tumor confluent with or extending into the ciliary body, choroid, or both, with scleral extension. (from AJCC 8th Ed.)
Iris melanoma with extrascleral extension. (from AJCC 8th Ed.)
Iris melanoma with extrascleral extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Iris melanoma with extrascleral extension more than 5 mm in largest diameter. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of choroidal and ciliary body melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Choroidal and ciliary body melanoma, tumor size category 1. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 1 without ciliary body involvement and extraocular extension. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 1 with ciliary body involvement. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 1 without ciliary body involvement but with extraocular extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 1 with ciliary body involvement and extraocular extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 2. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 2 without ciliary body involvement and extraocular extension. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 2 with ciliary body involvement. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 2 without ciliary body involvement but with extraocular extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 2 with ciliary body involvement and extraocular extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 3. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 3 without ciliary body involvement and extraocular extension. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 3 with ciliary body involvement. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 3 without ciliary body involvement but with extraocular extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 3 with ciliary body involvement and extraocular extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 4. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 4 without ciliary body involvement and extraocular extension. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 4 with ciliary body involvement. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 4 without ciliary body involvement but with extraocular extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, tumor size category 4 with ciliary body involvement and extraocular extension 5 mm or less in largest diameter. (from AJCC 8th Ed.)
Choroidal and ciliary body melanoma, any tumor size category with extraocular extension more than 5 mm in largest diameter. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of uveal melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Uveal melanoma with regional lymph node metastasis or discrete tumor deposits in the orbit. (from AJCC 8th Ed.)
Uveal melanoma with metastasis in one or more regional lymph node(s). (from AJCC 8th Ed.)
Uveal melanoma in which no regional lymph nodes are positive, but there are discrete tumor deposits in the orbit that are not contiguous to the eye. (from AJCC 8th Ed.)
A term that refers to the staging of choroidal and ciliary body melanoma, following the rules of the TNM AJCC v8 classification system.
Stage I includes: T1a, N0, M0. T1a: Tumor size category 1 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage II includes: IIA (T1b-d, N0, M0); (T2a, N0, M0); IIB (T2b, N0, M0); (T3a, N0, M0). T1b: Tumor size category 1 with ciliary body involvement. T1c: Tumor size category 1 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in largest diameter. T1d: Tumor size category 1 with ciliary body involvement and extraocular extension less than or equal to 5 mm in largest diameter. T2a: Tumor size category 2 without ciliary body involvement and extraocular extension. T2b: Tumor size category 2 with ciliary body involvement. T3a: Tumor size category 3 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIA includes: (T1b-d, N0, M0); (T2a, N0, M0). T1b: Tumor size category 1 with ciliary body involvement. T1c: Tumor size category 1 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in largest diameter. T1d: Tumor size category 1 with ciliary body involvement and extraocular extension less than or equal to 5 mm in largest diameter. T2a: Tumor size category 2 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIB includes: (T2b, N0, M0); (T3a, N0, M0). T2b: Tumor size category 2 with ciliary body involvement. T3a: Tumor size category 3 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage III includes: IIIA (T2c-d, N0, M0); (T3b-c, N0, M0); (T4a, N0, M0); IIIB (T3d, N0, M0); (T4b-c, N0, M0); IIIC: (T4d-e, N0, M0). T2c: Tumor size category 2 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in largest diameter. T2d: Tumor size category 2 with ciliary body involvement and extraocular extension less than or equal to 5 mm in largest diameter. T3b: Tumor size category 3 with ciliary body involvement. T3c: Tumor size category 3 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in largest diameter. T4a: Tumor size category 4 without ciliary body involvement and extraocular extension. T3d: Tumor size category 3 with ciliary body involvement and extraocular extension less than or equal to 5 mm in largest diameter. T4b: Tumor size category 4 with ciliary body involvement. T4c: Tumor size category 4 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in largest diameter. T4d: Tumor size category 4 with ciliary body involvement and extraocular extension less than or equal to 5 mm in largest diameter. T4e: Any tumor size category with extraocular extension more than 5 mm in largest diameter. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIB includes: (T3d, N0, M0); (T4b-c, N0, M0). T3d: Tumor size category 3 with ciliary body involvement and extraocular extension less than or equal to 5 mm in largest diameter. T4b: Tumor size category 4 with ciliary body involvement. T4c: Tumor size category 4 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in largest diameter. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IIIC includes: T4d-e, N0, M0. T4d: Tumor size category 4 with ciliary body involvement and extraocular extension less than or equal to 5 mm in largest diameter. T4e: Any tumor size category with extraocular extension more than 5 mm in largest diameter. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Stage IV includes: (Any T, N1, M0); (Any T, Any N, M1a-c). N1: Regional lymph node metastasis or discrete tumor deposits in the orbit. M0: No distant metastasis. M1a: Distant metastasis, with the largest diameter of the largest metastasis measuring 3 cm or less. M1b: Distant metastasis, with the largest diameter of the largest metastasis measuring 3.1-8.0 cm. M1c: Distant metastasis, with the largest diameter of the largest metastasis measuring 8.1 cm or more. (AJCC 8th ed.)
Partial response or complete response in at least one component (i.e., soft tissue, bone, and bone marrow disease) but at least one other component with stable disease; no component with progressive disease. (J Clin Oncol 35: 2580-2587, 2017)
Any component (i.e., soft tissue, bone, and bone marrow disease) with progressive disease. (J Clin Oncol 35: 2580-2587, 2017)
A term that refers to the staging of uveal melanoma, following the rules of the TNM AJCC v7 classification system.
A finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system. This classification does not apply to central nervous system component of ""trilateral retinoblastoma"" (is staged according to the classification for brain and spinal cord), retinoma (or retinocytoma) (no AJCC staging system), and medulloepithelioma (no AJCC staging system). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Retinoblastoma with no signs or symptoms of intracranial or distant metastasis. (from AJCC 8th Ed.)
Retinoblastoma with distant metastasis without microscopic confirmation. (from AJCC 8th Ed.)
Retinoblastoma with tumor(s) involving any distant site (e.g., bone marrow, liver) on clinical or radiologic tests. (from AJCC 8th Ed.)
Retinoblastoma with tumor involving the CNS on radiologic imaging (not including trilateral retinoblastoma). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor. Each eye is scored for cT criteria, and the cT category for the patient is based on the most advanced eye. (from AJCC 8th Ed.)
Unknown evidence of intraocular tumor. (from AJCC 8th Ed.)
No evidence of intraocular tumor. (from AJCC 8th Ed.)
Intraretinal tumor(s) with subretinal fluid 5 mm or less from the base of any tumor. (from AJCC 8th Ed.)
Tumors 3 mm or less and further than 1.5 mm from disc and fovea. (from AJCC 8th Ed.)
Tumors more than 3 mm or closer than 1.5 mm from disc and fovea. (from AJCC 8th Ed.)
Intraocular tumor(s) with retinal detachment, vitreous seeding, or subretinal seeding. (from AJCC 8th Ed.)
Subretinal fluid more than 5 mm from the base of any tumor. (from AJCC 8th Ed.)
Vitreous seeding and/or subretinal seeding. (from AJCC 8th Ed.)
Advanced intraocular tumor(s). (from AJCC 8th Ed.)
Phthisis or pre-phthisis bulbi. (from AJCC 8th Ed.)
Raised intraocular pressure with neovascularization and/or buphthalmos. (from AJCC 8th Ed.)
Hyphema and/or massive vitreous hemorrhage. (from AJCC 8th Ed.)
Aseptic orbital cellulitis. (from AJCC 8th Ed.)
Extraocular tumor(s) involving orbit, including optic nerve. (from AJCC 8th Ed.)
Radiologic evidence of retrobulbar optic nerve involvement or thickening of optic nerve or involvement of orbital tissues. (from AJCC 8th Ed.)
Extraocular tumor clinically evident with proptosis and/or an orbital mass. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Retinoblastoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Retinoblastoma with no regional lymph node involvement. (from AJCC 8th Ed.)
Retinoblastoma with evidence of preauricular, submandibular, and cervical lymph node involvement. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Retinoblastoma with distant metastasis with microscopic confirmation. (from AJCC 8th Ed.)
Retinoblastoma with pathological evidence of tumor at any distant site (e.g., bone marrow, liver, or other). (from AJCC 8th Ed.)
Retinoblastoma with pathological evidence of tumor in the cerebrospinal fluid or CNS parenchyma. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Retinoblastoma in which regional lymph node involvement cannot be assessed. (from AJCC 8th Ed.)
Retinoblastoma with no lymph node involvement. (from AJCC 8th Ed.)
Retinoblastoma with regional lymph node involvement. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of retinoblastoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Intraocular tumor(s) without any local invasion, focal choroidal invasion, or pre-or intralaminar involvement of the optic nerve head. (from AJCC 8th Ed.)
Intraocular tumor(s) with local invasion. (from AJCC 8th Ed.)
Concomitant focal choroidal invasion and pre-or intralaminar involvement of the optic nerve head. (from AJCC 8th Ed.)
Tumor invasion of stroma of iris and/or trabecular meshwork and/or Schlemm's canal. (from AJCC 8th Ed.)
Intraocular tumor(s) with significant local invasion. (from AJCC 8th Ed.)
Massive choroidal invasion (more than 3 mm in largest diameter, or multiple foci of focal choroidal involvement totaling more than 3 mm, or any full-thickness choroidal involvement). (from AJCC 8th Ed.)
Retrolaminar invasion of the optic nerve head, not involving the transected end of the optic nerve. (from AJCC 8th Ed.)
Any partial-thickness involvement of the sclera within the inner two thirds. (from AJCC 8th Ed.)
Full-thickness invasion into the outer third of the sclera and/or invasion into or around emissary channels. (from AJCC 8th Ed.)
Evidence of extraocular tumor: tumor at the transected end of the optic nerve, tumor in the meningeal spaces around the optic nerve, full-thickness invasion of the sclera with invasion of the episclera, adjacent adipose tissue, extraocular muscle, bone, conjunctiva, or eyelids. (from AJCC 8th Ed.)
A finding about a heritable trait of retinoblastoma, following the rules of the AJCC v8 classification system.
Unknown or insufficient evidence of a constitutional RB1 gene mutation. (from AJCC 8th Ed.)
Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. (from AJCC 8th Ed.)
Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (from AJCC 8th Ed.)
A term that refers to the staging of retinoblastoma according to the American Joint Committee on Cancer, 8th edition. This staging system does not apply to central nervous system component of ""trilateral retinoblastoma"" (is staged according to the classification for brain and spinal cord), retinoma (or retinocytoma) (no AJCC staging system), and medulloepithelioma (no AJCC staging system). (from AJCC 8th Ed.)
A term that refers to the clinical staging of retinoblastoma according to the American Joint Committee on Cancer, 8th edition.
Stage I includes: cT1, cT2, cT3, cN0, cM0, Any H. cT1: Intraretinal tumor(s) with subretinal fluid 5 mm or less from the base of any tumor. cT2: Intraocular tumor(s) with retinal detachment, vitreous seeding, or subretinal seeding. cT3: Advanced intraocular tumor(s). cN0: No regional lymph node involvement. cM0: No signs or symptoms of intracranial or distant metastasis. HX: Unknown or insufficient evidence of a constitutional RB1 gene mutation. H0: Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. H1: Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (AJCC 8th ed.)
Stage II includes: cT4a, cN0, cM0, Any H. cT4a: Radiologic evidence of retrobulbar optic nerve involvement or thickening of optic nerve or involvement of orbital tissues. cN0: No regional lymph node involvement. cM0: No signs or symptoms of intracranial or distant metastasis. HX: Unknown or insufficient evidence of a constitutional RB1 gene mutation. H0: Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. H1: Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (AJCC 8th ed.)
Stage III includes: (cT4b, cN0, cM0, Any H); (Any cT, cN1, cM0, Any H). cT4b: Extraocular tumor clinically evident with proptosis and/or an orbital mass. cN0: No regional lymph node involvement. cN1: Evidence of preauricular, submandibular, and cervical lymph node involvement. cM0: No signs or symptoms of intracranial or distant metastasis. HX: Unknown or insufficient evidence of a constitutional RB1 gene mutation. H0: Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. H1: Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (AJCC 8th ed.)
Stage IV includes: Any cT, Any N, cM1 or pM1, Any H. cM1: Distant metastasis without microscopic confirmation. pM1: Distant metastasis with microscopic confirmation. HX: Unknown or insufficient evidence of a constitutional RB1 gene mutation. H0: Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. H1: Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (AJCC 8th ed.)
A term that refers to the pathologic staging of retinoblastoma according to the American Joint Committee on Cancer, 8th edition.
Stage I includes: pT1, pT2, pT3, pN0, cM0, Any H. pT1: Intraocular tumor(s) without any local invasion, focal choroidal invasion, or pre-or intralaminar involvement of the optic nerve head. pT2: Intraocular tumor(s) with local invasion. pT3: Intraocular tumor(s) with significant local invasion. pN0: No lymph node involvement. cM0: No signs or symptoms of intracranial or distant metastasis. HX: Unknown or insufficient evidence of a constitutional RB1 gene mutation. H0: Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. H1: Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (AJCC 8th ed.)
Stage II includes: pT4, pN0, cM0, Any H. pT4: Evidence of extraocular tumor: tumor at the transected end of the optic nerve, tumor in the meningeal spaces around the optic nerve, full-thickness invasion of the sclera with invasion of the episclera, adjacent adipose tissue, extraocular muscle, bone, conjunctiva, or eyelids. pN0: No lymph node involvement. cM0: No signs or symptoms of intracranial or distant metastasis. HX: Unknown or insufficient evidence of a constitutional RB1 gene mutation. H0: Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. H1: Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (AJCC 8th ed.)
Stage III includes: Any pT, pN1, cM0, Any H. pN1: Regional lymph node involvement. cM0: No signs or symptoms of intracranial or distant metastasis. HX: Unknown or insufficient evidence of a constitutional RB1 gene mutation. H0: Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. H1: Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (AJCC 8th ed.)
Stage IV includes: Any pT, Any N, cM1 or pM1, Any H. cM1: Distant metastasis without microscopic confirmation. pM1: Distant metastasis with microscopic confirmation. HX: Unknown or insufficient evidence of a constitutional RB1 gene mutation. H0: Normal RB1 alleles in blood tested with demonstrated high-sensitivity assays. H1: Bilateral retinoblastoma, retinoblastoma with an intracranial primitive neuroectodermal tumor (i.e., trilateral retinoblastoma), patient with family history of retinoblastoma, or molecular definition of a constitutional RB1 gene mutation. (AJCC 8th ed.)
A finding about one or more characteristics of carcinomas of the lacrimal gland, following the rules of the TNM AJCC v8 classification system. There is no AJCC staging system for carcinomas of the nasolacrimal sac. Lymphomas are staged according to the classification for ocular adnexal lymphomas. No stage groupings are currently recommended for lacrimal gland carcinomas. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of lacrimal gland carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of lacrimal gland carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Lacrimal gland carcinoma with no distant metastasis. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of lacrimal gland carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of lacrimal gland carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Primary tumor cannot be assessed. (from AJCC 8th Ed.)
No evidence of primary tumor. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring 2 cm or less in greatest dimension with or without extraglandular extension into the orbital soft tissue. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring 2 cm or less in greatest dimension with or without extraglandular extension into the orbital soft tissue with no periosteal or bone involvement. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring 2 cm or less in greatest dimension with or without extraglandular extension into the orbital soft tissue with periosteal involvement only. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring 2 cm or less in greatest dimension with or without extraglandular extension into the orbital soft tissue with periosteal and bone involvement. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring more than 2 cm but 4 cm or less in greatest dimension. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring more than 2 cm but 4 cm or less in greatest dimension with no periosteal or bone involvement. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring more than 2 cm but 4 cm or less in greatest dimension with periosteal involvement only. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring more than 2 cm but 4 cm or less in greatest dimension with periosteal and bone involvement. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring more than 4 cm in greatest dimension. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring more than 4 cm in greatest dimension with no periosteal or bone involvement. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring more than 4 cm in greatest dimension with periosteal involvement only. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with tumor measuring more than 4 cm in greatest dimension with periosteal and bone involvement. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with involvement of adjacent structures, including sinuses, temporal fossa, pterygoid fossa, superior orbital fissure, cavernous sinus, or brain. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with involvement of adjacent structures, including sinuses, temporal fossa, pterygoid fossa, superior orbital fissure, cavernous sinus, or brain and measuring 2 cm or less in greatest dimension. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with involvement of adjacent structures, including sinuses, temporal fossa, pterygoid fossa, superior orbital fissure, cavernous sinus, or brain and measuring more than 2 cm but 4 cm or less in greatest dimension. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with involvement of adjacent structures, including sinuses, temporal fossa, pterygoid fossa, superior orbital fissure, cavernous sinus, or brain and measuring more than 4 cm in greatest dimension. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of lacrimal gland carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Lacrimal gland carcinoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with no regional lymph node metastasis. (from AJCC 8th Ed.)
Lacrimal gland carcinoma with regional lymph node metastasis. (from AJCC 8th Ed.)
A finding about one or more characteristics of orbital sarcoma, following the rules of the TNM AJCC v8 classification system. This classification does not apply to osseous and cartilaginous tumors arising in bone (are staged according to the classification for bone), secondary tumors that arise in adjacent periorbital sites with orbital invasion (are staged according to the classification for primary site of tumor), lacrimal gland carcinomas (are staged according to the classification for lacrimal gland carcinoma), and lacrimal gland sarcomas (are staged according to the classification for soft tissue sarcoma of the head and neck). There is no proposal for anatomic stage and prognostic groups for orbital sarcomas at this time. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of orbital sarcoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of orbital sarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Orbital sarcoma with no distant metastasis. (from AJCC 8th Ed.)
Orbital sarcoma with distant metastasis. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of orbital sarcoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of orbital sarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of orbital sarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Orbital sarcoma with tumor measuring 2 cm or less in greatest dimension. (from AJCC 8th Ed.)
Orbital sarcoma with tumor measuring more than 2 cm in greatest diameter without invasion of bony walls or globe. (from AJCC 8th Ed.)
Orbital sarcoma with tumor of any size with invasion of bony walls. (from AJCC 8th Ed.)
Orbital sarcoma with tumor of any size with invasion of globe or periorbital structures, including eyelid, conjunctiva, temporal fossa, nasal cavity, paranasal sinuses, and/or central nervous system. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of orbital sarcoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Orbital sarcoma in which the regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
Orbital sarcoma with no regional lymph node metastasis. (from AJCC 8th Ed.)
Orbital sarcoma with regional lymph node metastasis. (from AJCC 8th Ed.)
A finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v8 classification system. The lymphomas staged according to this system are primary lymphomas arising in the ocular adnexa-namely, the conjunctiva, eyelids, lacrimal gland, lacrimal drainage apparatus, and other orbital tissues surrounding the eye. Secondary ocular adnexal lymphomas and intraocular lymphomas are staged according to the classification for Hodgkin and non-Hodgkin lymphoma. There is no prognostic stage grouping for ocular adnexal lymphomas. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Ocular adnexal lymphoma with no evidence of involvement of other extranodal sites. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with noncontiguous involvement of tissues or organs external to the ocular adnexa (e.g., parotid glands, submandibular gland, lung, liver, spleen, kidney, breast). (from AJCC 8th Ed.)
Ocular adnexal lymphoma with lymphomatous involvement of the bone marrow. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with both M1a and M1b involvement. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Lymphoma extent not specified. (from AJCC 8th Ed.)
No evidence of lymphoma. (from AJCC 8th Ed.)
Ocular adnexal lymphoma involving the conjunctiva alone without eyelid or orbital involvement. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with orbital involvement with or without conjunctival involvement. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with preseptal eyelid involvement with or without orbital involvement and with or without conjunctival involvement. (from AJCC 8th Ed.)
Orbital adnexal lymphoma and extraorbital lymphoma extending beyond the orbit to adjacent structures, such as bone, maxillofacial sinuses, and brain. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of ocular adnexal lymphoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Involvement of lymph nodes not assessed. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with no evidence of lymph node involvement. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with involvement of lymph node region or regions draining the ocular adnexal structures and superior to the mediastinum (preauricular, parotid, submandibular, and cervical nodes). (from AJCC 8th Ed.)
Ocular adnexal lymphoma with involvement of a single lymph node region superior to the mediastinum. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with involvement of two or more lymph node regions, superior to the mediastinum. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with involvement of lymph node regions of the mediastinum. (from AJCC 8th Ed.)
Ocular adnexal lymphoma with diffuse or disseminated involvement of peripheral and central lymph node regions. (from AJCC 8th Ed.)
A finding about one or more characteristics of endocrine system cancer, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of thyroid carcinoma, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of papillary, follicular, Hurthle cell, poorly differentiated, and anaplastic (undifferentiated) thyroid carcinoma, following the rules of the TNM AJCC v8 classification system. Medullary thyroid cancers are staged according to the classification for thyroid-medullary. Thyroid lymphomas are staged according to the classification for Hodgkin and non-Hodgkin lymphoma. There are no AJCC staging systems for thyroid cancer arising from thyroglossal duct cyst and thyroid cancer in malignant struma ovarii. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of papillary, follicular, Hurthle cell, poorly differentiated, and anaplastic thyroid carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of papillary, follicular, Hurthle cell, poorly differentiated, and anaplastic thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
No distant metastasis. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of papillary, follicular, Hurthle cell, poorly differentiated, and anaplastic thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Regional lymph nodes cannot be assessed. (from AJCC 8th Ed.)
No evidence of locoregional lymph node metastasis. (from AJCC 8th Ed.)
No radiologic or clinical evidence of locoregional lymph node metastasis. (from AJCC 8th Ed.)
Metastasis to regional nodes. (from AJCC 8th Ed.)
Metastasis to level VI or VII (pretracheal, paratracheal, or prelaryngeal /Delphian, or upper mediastinal) lymph nodes. This can be unilateral or bilateral disease. (from AJCC 8th Ed.)
Metastasis to unilateral, bilateral, or contralateral lateral neck lymph nodes (levels I, II, III, IV, or V) or retropharyngeal lymph nodes. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of papillary, follicular, Hurthle cell, poorly differentiated, and anaplastic thyroid carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of papillary, follicular, Hurthle cell, poorly differentiated, and anaplastic thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of papillary, follicular, Hurthle cell, poorly differentiated, and anaplastic thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. (from AJCC 8th Ed.)
Tumor measuring 1 cm or less in greatest dimension limited to the thyroid. (from AJCC 8th Ed.)
Tumor measuring more than 1 cm but 2 cm or less in greatest dimension limited to the thyroid. (from AJCC 8th Ed.)
Tumor measuring more than 2 cm but 4 cm or less in greatest dimension limited to the thyroid. (from AJCC 8th Ed.)
Tumor measuring more than 4 cm in greatest dimension limited to the thyroid, or gross extrathyroidal extension invading only strap muscles. (from AJCC 8th Ed.)
Tumor measuring more than 4 cm in greatest dimension limited to the thyroid. (from AJCC 8th Ed.)
Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles) from a tumor of any size. (from AJCC 8th Ed.)
Tumor of any size with gross extrathyroidal extension. (from AJCC 8th Ed.)
Gross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve from a tumor of any size. (from AJCC 8th Ed.)
Gross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels from a tumor of any size. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of papillary, follicular, Hurthle cell, poorly differentiated, and anaplastic thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
One or more cytologically or histologically confirmed benign lymph nodes. (from AJCC 8th Ed.)
Metastasis to level VI or VII (pretracheal, paratracheal, or prelaryngeal/Delphian, or upper mediastinal) lymph nodes. This can be unilateral or bilateral disease. (from AJCC 8th Ed.)
A term that refers to the staging of follicular thyroid gland carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of differentiated thyroid gland carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of papillary thyroid gland carcinoma, following the rules of the TNM AJCC v7 classification system.
A differentiated thyroid gland carcinoma stage for patients under 45 years of age defined according to the AJCC 7th edition criteria.
A differentiated thyroid gland carcinoma stage for patients under 55 years of age defined according to the AJCC 8th edition criteria.
A differentiated thyroid gland carcinoma stage for patients 45 years and older defined according to the AJCC 7th edition criteria.
A differentiated thyroid gland carcinoma stage for patients 55 years and older defined according to the AJCC 8th edition criteria.
A term that refers to the staging of differentiated thyroid gland carcinoma, following the rules of the TNM AJCC v8 classification system.
Stage I includes: Any T, Any N, M0. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage I includes: (T1, N0/NX, M0); (T2, N0/NX, M0). T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but 4 cm or less in greatest dimension limited to the thyroid. N0: No evidence of locoregional lymph node metastasis. NX: Regional lymph nodes cannot be assessed. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage II includes: Any T, Any N, M1. M1: Distant metastasis. (from AJCC 8th Ed.)
Stage II includes: (T1, N1, M0); (T2, N1, M0); (T3a/T3b, Any N, M0). T1: Tumor measuring 2 cm or less in greatest dimension limited to the thyroid. T2: Tumor measuring more than 2 cm but 4 cm or less in greatest dimension limited to the thyroid. T3a: Tumor measuring more than 4 cm in greatest dimension limited to the thyroid. T3b: Gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid, or omohyoid muscles) from a tumor of any size. N1: Metastasis to regional nodes. M0: No distant metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of papillary thyroid gland carcinoma, following the rules of the TNM AJCC v8 classification system.
A term that refers to the staging of follicular thyroid gland carcinoma, following the rules of the TNM AJCC v8 classification system.
A term that refers to the staging of thyroid gland undifferentiated (anaplastic) carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of thyroid gland undifferentiated (anaplastic) carcinoma, following the rules of the TNM AJCC v8 classification system.
A finding about one or more characteristics of medullary thyroid carcinoma, following the rules of the TNM AJCC v8 classification system. Differentiated and anaplastic thyroid carcinomas are staged according to the classification for thyroid-differentiated and anaplastic carcinoma. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of medullary thyroid carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of medullary thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A clinical finding about one or more characteristics of medullary thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Metastasis to unilateral, bilateral, or contralateral lateral neck lymph node levels I, II, III, IV, or V or retropharyngeal lymph nodes. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of medullary thyroid carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of medullary thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of medullary thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Tumor measuring more than 2 cm but less than 4 cm in greatest dimension limited to the thyroid. (from AJCC 8th Ed.)
Tumor measuring 4 cm or more in greatest dimension or with extrathyroidal extension. (from AJCC 8th Ed.)
Tumor measuring 4 cm or more in greatest dimension limited to the thyroid. (from AJCC 8th Ed.)
Tumor of any size with gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyrohyoid or omohyoid muscles). (from AJCC 8th Ed.)
Moderately advanced disease; tumor of any size with gross extrathyroidal extension into the nearby tissues of the neck, including subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve. (from AJCC 8th Ed.)
Very advanced disease; tumor of any size with extension towards the spine or into nearby large blood vessels, invading the prevertebral fascia, or encasing the carotid artery or mediastinal vessels. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of medullary thyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Metastasis to unilateral, bilateral, or contralateral lateral neck lymph nodes levels I, II, III, IV, or V or retropharyngeal lymph nodes. (from AJCC 8th Ed.)
A term that refers to the staging of thyroid gland medullary carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of thyroid gland medullary carcinoma, following the rules of the TNM AJCC v8 classification system. Differentiated and anaplastic thyroid gland carcinomas are staged according to the classification for thyroid-differentiated and anaplastic carcinoma. (from AJCC 8th Ed.)
A finding about one or more characteristics of parathyroid carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of parathyroid carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of parathyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of parathyroid carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of parathyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of parathyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Atypical parathyroid neoplasm (neoplasm of uncertain malignant potential). (from AJCC 8th Ed.)
Tumor localized to the parathyroid gland with extension limited to soft tissue. (from AJCC 8th Ed.)
Tumor with direct invasion into the thyroid gland. (from AJCC 8th Ed.)
Tumor with direct invasion into recurrent laryngeal nerve, esophagus, trachea, skeletal muscle, adjacent lymph nodes, or thymus. (from AJCC 8th Ed.)
Tumor with direct invasion into major blood vessel or spine. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of parathyroid carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
No regional lymph node metastasis. (from AJCC 8th Ed.)
Regional lymph node metastasis. (from AJCC 8th Ed.)
Metastasis to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes), or superior mediastinal lymph nodes (level VII). (from AJCC 8th Ed.)
Metastasis to unilateral, bilateral, or contralateral cervical (levels I, II, III, IV, or V) or retropharyngeal nodes. (from AJCC 8th Ed.)
An inhibitor of the extracellular signal-regulated kinases (ERK) 1 and 2, with potential antineoplastic activity. Upon intravenous administration, KO-947 specifically binds to and inhibits both ERK 1 and 2, thereby preventing the activation of mitogen-activated protein kinase (MAPK)/ERK-mediated signal transduction pathways. This results in the inhibition of ERK-dependent tumor cell proliferation and survival. The MAPK/ERK pathway is often upregulated in a variety of tumor cell types and plays a key role in the proliferation, differentiation and survival of tumor cells.
Lung carcinoma that does not respond to treatment.
Extensive stage small cell lung carcinoma that has reemerged after a period of remission.
Extensive stage small cell lung carcinoma that does not respond to treatment.
A finding about one or more characteristics of adrenal cortical carcinoma, following the rules of the TNM AJCC v8 classification system. Adrenal medullary pheochromocytoma is staged according to the classification for adrenal neuroendocrine tumors. There is no AJCC staging system for neuroblastic tumors of the adrenal gland. (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of adrenal cortical carcinoma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of adrenal cortical carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of adrenal cortical carcinoma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of adrenal cortical carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of adrenal cortical carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Tumor measuring 5 cm or less in greatest dimension, with no extra-adrenal invasion. (from AJCC 8th Ed.)
Tumor measuring more than 5 cm in greatest dimension, with no extra-adrenal invasion. (from AJCC 8th Ed.)
Tumor of any size with local invasion but not invading adjacent organs. (from AJCC 8th Ed.)
Tumor of any size that invades adjacent organs (kidney, diaphragm, pancreas, spleen, or liver) or large blood vessels (renal vein or vena cava). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of adrenal cortical carcinoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
Metastasis in regional lymph node(s). (from AJCC 8th Ed.)
A term that refers to the staging of adrenal cortex carcinoma, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of adrenal cortex carcinoma, following the rules of the TNM AJCC v8 classification system. Adrenal medullary pheochromocytoma is staged according to the classification for adrenal neuroendocrine tumors. There is no AJCC staging system for neuroblastic tumors of the adrenal gland. (from AJCC 8th Ed.)
A finding about one or more characteristics of pheochromocytoma and paraganglioma, following the rules of the TNM AJCC v8 classification system. This classification system applies to the adrenal medulla pheochromocytomas and sympathetic paragangliomas. Parasympathetic paragangliomas are not staged because they are largely benign. This staging system does not apply to neuroendocrine tumors of the pancreas (are staged according to the classification for neuroendocrine tumors of the pancreas) and carotid body tumors (not staged). (from AJCC 8th Ed.)
A clinical finding about one or more characteristics of pheochromocytoma and paraganglioma, following the rules of the TNM AJCC v8 classification system.
A clinical finding about one or more characteristics of pheochromocytoma and paraganglioma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
Distant metastasis to only bone. (from AJCC 8th Ed.)
Distant metastasis to only distant lymph nodes/liver or lung. (from AJCC 8th Ed.)
Distant metastasis to bone plus multiple other sites. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of pheochromocytoma and paraganglioma, following the rules of the TNM AJCC v8 classification system.
A pathologic finding about one or more characteristics of pheochromocytoma and paraganglioma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases.
A pathologic finding about one or more characteristics of pheochromocytoma and paraganglioma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Pheochromocytoma measuring less than 5 cm in greatest dimension, with no extra-adrenal invasion. (from AJCC 8th Ed.)
Pheochromocytoma measuring 5 cm or more in greatest dimension or paraganglioma-sympathetic of any size, with no extra-adrenal invasion. (from AJCC 8th Ed.)
Tumor of any size with invasion into surrounding tissues (e.g., liver, pancreas, spleen, kidneys). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of pheochromocytoma and paraganglioma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
No lymph node metastasis. (from AJCC 8th Ed.)
A term that refers to the staging of adrenal gland pheochromocytoma and sympathetic paraganglioma, following the rules of the TNM AJCC v8 classification system. Parasympathetic paragangliomas are not staged because they are largely benign. This staging system does not apply to neuroendocrine tumors of the pancreas (are staged according to the classification for neuroendocrine tumors of the pancreas) and carotid body tumors (not staged). (from AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Pheochromocytoma measuring less than 5 cm in greatest dimension, with no extra-adrenal invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage II includes: T2, N0, M0. T2: Pheochromocytoma measuring 5 cm or more in greatest dimension or paraganglioma-sympathetic of any size, with no extra-adrenal invasion. N0: No regional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
Stage III includes: (T1, N1, M0); (T2, N1, M0); (T3, Any N, M0). T1: Pheochromocytoma measuring less than 5 cm in greatest dimension, with no extra-adrenal invasion. T2: Pheochromocytoma measuring 5 cm or more in greatest dimension or paraganglioma-sympathetic of any size, with no extra-adrenal invasion. T3: Tumor of any size with invasion into surrounding tissues (e.g., liver, pancreas, spleen, kidneys). N1: Regional lymph node metastasis. M0: No distant metastasis. (from AJCC 8th Ed.)
An orally available inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with potential immunomodulating and antineoplastic activities. Upon administration, IDO1 inhibitor BMS-986205 specifically targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the amino acid tryptophan into the immunosuppressive metabolite kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, BMS-986205 restores and promotes the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells, thereby inhibiting the growth of IDO1-expressing tumor cells. IDO1, overexpressed by multiple tumor cell types, plays an important role in immunosuppression. Tryptophan depletion inhibits T-lymphocyte proliferation and activation, and subsequently suppresses the immune system.
Any agent that inhibits the activity of the receptor tyrosine kinase anaplastic lymphoma kinase (ALK).
An anatomic stage for Hodgkin and non-Hodgkin lymphomas based on the Ann Arbor classification criteria.
An anatomic stage for non-Hodgkin lymphomas based on the Ann Arbor classification criteria.
An anatomic stage for Hodgkin lymphomas based on the Ann Arbor classification criteria.
A term that refers to the staging of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v7 classification system.
A term that refers to the staging of mycosis fungoides, following the rules of the TNM AJCC v7 classification system.
A staging system for adult Hodgkin and adult non-Hodgkin lymphomas based on the Lugano classification criteria. This staging system does not apply to ocular adnexal lymphomas (are staged according to the classification for ocular adnexal lymphoma), pediatric lymphomas (are staged according to the classification for pediatric lymphoma), primary cutaneous lymphomas (are staged according to the classification for primary cutaneous lymphoma), and multiple myelomas (are staged according to the classification for plasma cell myeloma). (from AJCC 8th Ed.)
Limited stage adult lymphoma based on the Lugano classification criteria. It includes stages I, IE, II, and IIE. (from AJCC 8th Ed.)
Stage I: Involvement of a single lymphatic site (i.e., nodal region, Waldeyer's ring, thymus, or spleen). (from AJCC 8th Ed.)
Stage IE: Single extralymphatic site in the absence of nodal involvement (rare in Hodgkin lymphoma). (from AJCC 8th Ed.)
Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm. (from AJCC 8th Ed.)
Stage IIE: Contiguous extralymphatic extension from a nodal site with or without involvement of other lymph node regions on the same side of the diaphragm. (from AJCC 8th Ed.)
Stage II Bulky: Stage II with disease bulk. (from AJCC 8th Ed.)
Stage III: Involvement of lymph node regions on both sides of the diaphragm; nodes above the diaphragm with spleen involvement. (from AJCC 8th Ed.)
Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement; or noncontiguous extralymphatic organ involvement in conjunction with nodal stage II disease; or any extralymphatic organ involvement in nodal stage III disease. Stage IV includes any involvement of the CSF, bone marrow, liver, or lungs (other than by direct extension in stage IIE disease). (from AJCC 8th Ed.)
A staging system for adult non-Hodgkin lymphomas based on the Lugano classification criteria. This staging system does not apply to ocular adnexal lymphomas (are staged according to the classification for ocular adnexal lymphoma), pediatric non-Hodgkin lymphomas (are staged according to the St. Jude Children's Research Hospital staging system), primary cutaneous lymphomas (are staged according to the classification for primary cutaneous lymphoma), and multiple myelomas (are staged according to the classification for plasma cell myeloma). (from AJCC 8th Ed.)
Limited stage adult non-Hodgkin lymphoma based on the Lugano classification criteria. It includes stages I, IE, II, and IIE. (from AJCC 8th Ed.)
Stage IE: Single extralymphatic site in the absence of nodal involvement. (from AJCC 8th Ed.)
Advanced stage adult non-Hodgkin lymphoma based on the Lugano classification criteria. It includes stages III and IV. (from AJCC 8th Ed.)
A staging system for Hodgkin lymphomas based on the Lugano classification criteria. Staging for childhood Hodgkin lymphoma is the same as for the adult counterpart. (from AJCC 8th Ed.)
Limited stage Hodgkin lymphoma based on the Lugano classification criteria. It includes stages I, IE, II, and IIE. (from AJCC 8th Ed.)
Advanced stage Hodgkin lymphoma based on the Lugano classification criteria. It includes stages III and IV. (from AJCC 8th Ed.)
A staging system for childhood Hodgkin lymphomas based on the Lugano classification criteria. Staging for childhood Hodgkin lymphoma is the same as for the adult counterpart. (from AJCC 8th Ed.)
Limited stage childhood Hodgkin lymphoma based on the Lugano classification criteria. It includes stages I, IE, II, and IIE. (from AJCC 8th Ed.)
Advanced stage childhood Hodgkin lymphoma based on the Lugano classification criteria. It includes stages III and IV. (from AJCC 8th Ed.)
Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement; or noncontiguous extralymphatic organ involvement in conjunction with nodal stage II disease; or any extralymphatic organ involvement in nodal stage III disease. Stage IV includes any involvement of the bone marrow, liver, or lungs (other than by direct extension in stage IIE disease). (from AJCC 8th Ed.)
A staging system for adult Hodgkin lymphomas based on the Lugano classification criteria. Staging for adult Hodgkin lymphoma is the same as for the childhood counterpart. (from AJCC 8th Ed.)
Limited stage adult Hodgkin lymphoma based on the Lugano classification criteria. It includes stages I, IE, II, and IIE. (from AJCC 8th Ed.)
Advanced stage adult Hodgkin lymphoma based on the Lugano classification criteria. It includes stages III and IV. (from AJCC 8th Ed.)
Staging systems for Hodgkin and non-Hodgkin lymphomas of childhood. Different systems are used for Hodgkin lymphoma and non-Hodgkin lymphoma of childhood. Staging of childhood Hodgkin lymphoma is the same as for the adult counterpart and is based on the Lugano classification criteria. The Ann Arbor staging system has been found to be inappropriate for staging of the non-Hodgkin lymphomas of childhood. The St. Jude staging system has been widely accepted and remains the recommended staging system for non-Hodgkin lymphomas of childhood. (from AJCC 8th Ed.)
A blood concentration of prostate specific antigen greater than or equal to 0.05 ng/mL.
A blood concentration of prostate specific antigen less than 0.7 ng/mL.
A term that refers to the staging of Hodgkin lymphoma and non-Hodgkin lymphoma according to the AJCC v8 classification guidelines.
A term that refers to the staging of chronic lymphocytic leukemia according to modified Rai staging system. This system is mainly used in North America.
A term that refers to the staging of chronic lymphocytic leukemia according to Binet staging system. This system is in wide use outside the United States.
Findings: Lymphocytosis only; Survival (months): more than 120. (from AJCC 8th Ed.)
Findings: Lymphocytosis and adenopathy; Survival (months): 95. (from AJCC 8th Ed.)
Findings: Lymphocytosis, adenopathy, and enlarged spleen and/or liver; Survival (months): 72. (from AJCC 8th Ed.)
A staging system for childhood non-Hodgkin Lymphomas based on the St. Jude Children's Research Hospital staging system. The Ann Arbor staging system has been found to be inappropriate for staging of the non-Hodgkin lymphomas of childhood. The St. Jude staging system has been widely accepted for more than three decades and remains the recommended staging system for childhood non-Hodgkin lymphomas. (from AJCC 8th Ed.)
Stage I: A single tumor (extranodal) or single anatomic area (nodal), with the exclusion of the mediastinum or abdomen. (from AJCC 8th Ed.)
Stage II: A single tumor (extranodal) with regional node involvement. Two or more nodal areas on the same side of the diaphragm. Two single (extranodal) tumors with or without regional node involvement on the same side of the diaphragm. A primary gastrointestinal tract tumor, usually in the ileocecal area, with or without involvement of associated mesenteric nodes only. (from AJCC 8th Ed.)
Stage III: Two single tumors (extranodal) on opposite sides of the diaphragm. Two or more nodal areas above and below the diaphragm. All the primary intrathoracic tumors (mediastinal, pleural, and thymic). All extensive primary intra-abdominal disease. All paraspinal or epidural tumors, regardless of other tumor site(s). (from AJCC 8th Ed.)
Stage IV: Any tumor, with initial CNS and/or bone marrow involvement. (from AJCC 8th Ed.)
An anatomic stage for lymphocyte-depleted classical Hodgkin lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for nodular sclerosis classical Hodgkin lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for mixed cellularity classical Hodgkin lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for adult Hodgkin lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for childhood Hodgkin lymphoma based on the Ann Arbor classification criteria.
A response indicating that an individual is able to eat a normal diet.
A response indicating that an individual is able to eat only some solid food.
A response indicating that an individual is able to eat only some semisolids.
A response indicating that an individual is able to only swallow liquids.
A change in the nucleotide sequence of a gene in the BRCA family that is associated with increased risk of disease.
A laboratory test result indicating that beta-2-microglobulin is present in a sample at concentrations exceeding 3 g/mL.
An anatomic stage for adult non-Hodgkin lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for childhood non-Hodgkin lymphoma based on the Ann Arbor classification criteria.
An irregularity in the structure of chromosome 13.
An indication that coma has lasted more than 24 hours.
A change in the nucleotide sequence of a receptor tyrosine kinase family gene.
An indication that death occurred on or within 90 days of a patient's initial admission to a hospital.
Delayed stomach emptying as a result of surgery.
An anatomic stage for B-cell non-Hodgkin lymphoma based on the Ann Arbor classification criteria.
A failure of function of a graft, flap, or prosthesis.
An indication that respiratory ventilation was in use for more than 48 hours.
An anatomic stage for T-cell non-Hodgkin lymphoma based on the Ann Arbor classification criteria.
A change in the nucleotide sequence of a gene involved in homologous recombination-type DNA repair processes that is associated with increased risk of disease.
An anatomic stage for B lymphoblastic lymphoma based on the Ann Arbor classification criteria.
A change in the nucleotide sequence of a CCAAT enhancer binding protein family gene.
A change in the nucleotide sequence of the RNF43 gene.
An anatomic stage for Burkitt lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for diffuse large B-cell lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for follicular lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for lymphoplasmacytic lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for marginal zone lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for small lymphocytic lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue based on the Ann Arbor classification criteria.
An anatomic stage for nodal marginal zone lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for mediastinal (thymic) large B-cell lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for centroblastic lymphoma based on the Ann Arbor classification criteria.
Cardiac arrest that is treated by CPR and/or defibrillation, regardless of outcome.
An anatomic stage for mature T- and NK-cell non-Hodgkin lymphomas based on the Ann Arbor classification criteria.
An inhibitor of Bruton's tyrosine kinase (BTK) with potential anti-inflammatory activity. Upon administration, poseltinib inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents the activation of BTK-mediated inflammatory pathways.
A molecular genetic abnormality indicating the presence of multiple copies of the AXL gene.
A change in the nucleotide sequence of the AXL gene.
An anatomic stage for adult T-cell leukemia/lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for noncutaneous anaplastic large cell lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for noncutaneous childhood anaplastic large cell lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for angioimmunoblastic T-cell lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for enteropathy-associated T-cell lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for nasal type NK/T-cell lymphoma based on the Ann Arbor classification criteria.
A semi-quantitative microscopic finding indicating that 30 percent or less of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A cancer vaccine consisting of a recombinant fowlpox viral (FPV) vector encoding both the two human tumor-associated antigens (TAAs) carcinoembryonic antigen (CEA) and mucin-1 (MUC-1), and TRICOM, which is comprised of the three human immune-enhancing co-stimulatory molecules B7-1, ICAM-1 and LFA-3, with potential immunostimulatory and antineoplastic activities. Upon subcutaneous administration following the administration of a proprietary modified vaccinia Ankara developed by Bavarian Nordic-based prime vaccine MVA-BN-CV301, the FPV vaccine CV301, which is used as a booster vaccine, activates a cytotoxic T-lymphocyte (CTL) response against CEA- and MUC-1-expressing tumor cells. In addition, the CV301-dependent anti-tumor CTL response upregulates the expression of programmed cell death ligand 1 (PD-L1); therefore, when FPV-CV301 is combined with a programmed cell death 1 (PD-1) immune checkpoint inhibitor, the antitumor effect may be increased. The TAAs CEA and MUC-1 are overexpressed in a variety of cancers.
A semi-quantitative microscopic finding indicating that 5 percent or more of the nucleated cells in a peripheral leukocyte sample are immature mononuclear cells.
A finding about one or more characteristics of primary cutaneous lymphoma [mycosis fungoides and Sezary syndrome (MF/SS) and primary cutaneous B-cell/T-cell (non-MF/SS) lymphomas], following the rules of the TNM v8 classification system. Both MF/SS and primary cutaneous B-cell/T-cell (non-MF/SS) lymphomas have TNM classification systems. MF/SS has a formal prognostic stage groups system proposed by the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organisation for Research and Treatment of Cancer (EORTC). There is no prognostic stage groups system for primary cutaneous B-cell/T-cell (non-MF/SS) lymphomas at this time. This classification system does not apply to eyelid skin lymphomas (are staged according to the classification for ocular adnexal lymphoma). (from AJCC 8th Ed.)
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v8 classification system. This classification is based on the ISCL/EORTC revision to the classification of mycosis fungoides and Sezary syndrome. (from AJCC 8th Ed.)
No visceral organ involvement. (from AJCC 8th Ed.)
Visceral involvement (must have pathology confirmation and organ involved should be specified). Note: for viscera, spleen and liver may be diagnosed by imaging criteria. (from AJCC 8th Ed.)
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v8 classification system as they pertain to staging of peripheral lymph nodes.
Clinically abnormal peripheral lymph nodes; no histologic confirmation. (from AJCC 8th Ed.)
No clinically abnormal peripheral lymph nodes; biopsy not required. Note: for node, abnormal peripheral lymph node(s) indicates any palpable peripheral node that on physical examination is firm, irregular, clustered, fixed or 1.5 cm or larger in diameter. Node groups examined on physical examination include cervical, supraclavicular, epitrochlear, axillary, and inguinal. Central nodes, which generally are not amenable to pathological assessment, currently are not considered in the nodal classification unless used to establish N3 histopathologically. (from AJCC 8th Ed.)
Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. Note: EORTC N1 classification includes: Dutch grade 1: dermatopathic lymphadenopathy. NCI LN0: no atypical lymphocytes. NCI LN1: occasional and isolated atypical lymphocytes (not arranged in clusters). NCI LN2: many atypical lymphocytes or lymphocytes in 3-6 cell clusters. (from AJCC 8th Ed.)
Clone negative. Note: A T-cell clone is defined by polymerase chain reaction (PCR) or Southern blot analysis of the TCR gene. (from AJCC 8th Ed.)
Clone positive. Note: A T-cell clone is defined by polymerase chain reaction (PCR) or Southern blot analysis of the TCR gene. (from AJCC 8th Ed.)
Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. Note: EORTC N2 classification includes Dutch grade 2: dermatopathic lymphadenopathy; early involvement by mycosis fungoides (presence of cerebriform nuclei less than 7.5 micrometers). NCI LN3: aggregates of atypical lymphocytes; nodal architecture preserved. (from AJCC 8th Ed.)
Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. Note: EORTC N3 classification includes: Dutch grade 3: partial effacement of lymph node architecture; many atypical cerebriform mononuclear cells. Dutch grade 4: complete effacement of lymph node. NCI LN4: partial/complete effacement of nodal architecture by atypical lymphocytes or frankly neoplastic cells. (from AJCC 8th Ed.)
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v8 classification system as they pertain to peripheral blood involvement.
Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). Note: for blood, Sezary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If Sezary cells cannot be used to determine tumor burden for B2, then one of the following modified ISCL criteria along with a positive clonal rearrangement of the TCR may be used instead: (1) expanded CD4+ or CD3+ cells with CD4/CD8 ratio of 10 or more, (2) expanded CD4+ cells with abnormal immunophenotype including loss of CD7 or CD26. (from AJCC 8th Ed.)
High blood tumor burden: 1,000 per microliter or more Sezary cells with positive clone. Note 1: for blood, Sezary cells are defined as lymphocytes with hyperconvoluted cerebriform nuclei. If Sezary cells cannot be used to determine tumor burden for B2, then one of the following modified ISCL criteria along with a positive clonal rearrangement of the TCR may be used instead: (1) expanded CD4+ or CD3+ cells with CD4/CD8 ratio of 10 or more, (2) expanded CD4+ cells with abnormal immunophenotype including loss of CD7 or CD26. Note 2: A T-cell clone is defined by PCR or Southern blot analysis of the T-cell receptor gene. (from AJCC 8th Ed.)
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor (skin).
Limited patches, papules, and/or plaques covering less than 10% of the skin surface. Note: for skin, patch indicates any size skin lesion without significant elevation or induration. Presence/absence of hypo- or hyperpigmentation, scale, crusting, and/or poikiloderma should be noted. Plaque indicates any size skin lesion that is elevated or indurated. Presence or absence of scale, crusting, and/or poikiloderma should be noted. Histologic features such as folliculotropism, large-cell transformation (more than 25% large cells), and CD30 positivity or negativity, as well as clinical features such as ulceration are important to document. (from AJCC 8th Ed.)
T1b (plaque +/- patch). (from AJCC 8th Ed.)
Patches, papules, or plaques covering 10% or more of the skin surface. (from AJCC 8th Ed.)
T2b (plaque +/- patch). (from AJCC 8th Ed.)
One or more tumors (equal or greater than 1 cm in diameter). Note: for skin, tumor indicates at least 1 cm diameter solid or nodular lesion with evidence of depth and/or vertical growth. Note the total number of lesions, total volume of lesions, largest size lesion, and region of body involved. Also note whether there is histologic evidence of large-cell transformation. Phenotyping for CD30 is encouraged. (from AJCC 8th Ed.)
Confluence of erythema covering 80% or more of body surface area. (from AJCC 8th Ed.)
A molecular genetic abnormality indicating the presence of multiple copies of the PIK3CB gene.
A change in the nucleotide sequence of the PIK3CB gene.
A term that refers to the staging of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v8 classification system. This prognostic stage groups system is based on the ISCL/EORTC revision to the staging of mycosis fungoides and Sezary syndrome. There is no prognostic stage groups system for primary cutaneous B-cell/T-cell (non-mycosis fungoides/Sezary syndrome) lymphomas at this time. This staging system does not apply to eyelid skin lymphomas (are staged according to the classification for ocular adnexal lymphoma). (from AJCC 8th Ed.)
Stage I includes: IA (T1, N0, M0, B0,1); IB (T2, N0, M0, B0,1). T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 8th ed.)
Stage IA includes: T1, N0, M0, B0,1. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 8th ed.)
Stage IB includes: T2, N0, M0, B0,1. T2: Patches, papules, or plaques covering 10% or more of the skin surface. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 8th ed.)
Stage II includes: IIA (T1,2, N1,2, M0, B0,1); IIB (T3, N0-2, M0, B0,1). T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. T3: One or more tumors (equal or greater than 1 cm in diameter). N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 8th ed.)
Stage IIA includes: T1-2, N1,2, M0, B0,1. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 8th ed.)
Stage IIB includes: T3, N0-2, M0, B0,1. T3: One or more tumors (equal or greater than 1 cm in diameter). N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 8th ed.)
Stage III includes: (T4, N0-2, M0, B0,1); IIIA (T4, N0-2, M0, B0); IIIB (T4, N0-2, M0, B1). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 8th ed.)
Stage IIIA includes: T4, N0-2, M0, B0. T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). (AJCC 8th ed.)
Stage IIIB includes: T4, N0-2, M0, B1. T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. (AJCC 8th ed.)
Stage IV includes: IVA1 (T1-4, N0-2, M0, B2); IVA2 (T1-4, N3, M0, B0-2); IVB (T1-4, N0-3, M1, B0-2). T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. T3: One or more tumors (equal or greater than 1 cm in diameter). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. M0: No visceral organ involvement. M1: Visceral involvement (must have pathology confirmation and organ involved should be specified). B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. B2: High blood tumor burden: 1,000 per microliter or more Sezary cells with positive clone. (AJCC 8th ed.)
Stage IVA1 includes: T1-4, N0-2, M0, B2. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. T3: One or more tumors (equal or greater than 1 cm in diameter). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. M0: No visceral organ involvement. B2: High blood tumor burden: 1,000 per microliter or more Sezary cells with positive clone. (AJCC 8th ed.)
Stage IVA2 includes: T1-4, N3, M0, B0-2. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. T3: One or more tumors (equal or greater than 1 cm in diameter). T4: Confluence of erythema covering 80% or more of body surface area. N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. M0: No visceral organ involvement. B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. B2: High blood tumor burden: 1,000 per microliter or more Sezary cells with positive clone. (AJCC 8th ed.)
Stage IVB includes: T1-4, N0-3, M1, B0-2. T1: Limited patches, papules, and/or plaques covering less than 10% of the skin surface. T2: Patches, papules, or plaques covering 10% or more of the skin surface. T3: One or more tumors (equal or greater than 1 cm in diameter). T4: Confluence of erythema covering 80% or more of body surface area. N0: No clinically abnormal peripheral lymph nodes; biopsy not required. N1: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 1 or National Cancer Institute (NCI) LN0-2. N2: Clinically abnormal peripheral lymph nodes; histopathology Dutch grade 2 or NCI LN3. N3: Clinically abnormal peripheral lymph nodes; histopathology Dutch grades 3-4 or NCI LN4; clone positive or negative. M1: Visceral involvement (must have pathology confirmation and organ involved should be specified). B0: Absence of significant blood involvement: 5% or less of peripheral blood lymphocytes are atypical (Sezary cells). B1: Low blood tumor burden: more than 5% of peripheral blood lymphocytes are atypical (Sezary cells) but does not meet the criteria of B2. B2: High blood tumor burden: 1,000 per microliter or more Sezary cells with positive clone. (AJCC 8th ed.)
A change in the nucleotide sequence of the AKT2 gene.
A molecular abnormality indicating the presence of an abnormally high level of the G1/S-specific cyclin-D2 protein.
A beta thalassemia resulting from an unequal crossover/recombination event involving portions of the delta and beta globin genes, resulting in underproduction of the abnormal delta-beta globin.
A molecular abnormality indicating the presence of an abnormally high level of the G1/S-specific cyclin-D3 protein.
A blood concentration of prostate specific antigen greater than 0.03 ng/mL.
A change in the nucleotide sequence of the ERBB3 gene that that results in constitutive activation of receptor tyrosine-protein kinase erbB-3 and its downstream signaling pathways.
A finding about one or more characteristics of primary cutaneous B-cell/T-cell [non-mycosis fungoides/Sezary syndrome (non-MF/SS)] lymphoma, following the rules of the TNM AJCC v8 classification system. There is no stage group system for non-MF/SS primary cutaneous lymphomas- including cutaneous T-cell, B-cell, and NK-cell lymphomas. (from AJCC 8th Ed.)
A finding about one or more characteristics of primary cutaneous B-cell/T-cell (non-MF/SS) lymphoma, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases. (from AJCC 8th Ed.)
No evidence of extracutaneous non-lymph node disease. (from AJCC 8th Ed.)
Extracutaneous non-lymph node disease present. (from AJCC 8th Ed.)
A finding about one or more characteristics of primary cutaneous B-cell/T-cell (non-MF/SS) lymphoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of regional lymph nodes.
No clinical or pathological lymph node involvement. (from AJCC 8th Ed.)
Involvement of one peripheral node region that drains an area of current or prior skin involvement. (from AJCC 8th Ed.)
Involvement of two or more peripheral node regions or involvement of any lymph node region that does not drain an area of current or prior skin involvement. (from AJCC 8th Ed.)
Involvement of central lymph nodes. (from AJCC 8th Ed.)
A finding about one or more characteristics of primary cutaneous B-cell/T-cell (non-MF/SS) lymphoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor (skin).
Solitary skin involvement. (from AJCC 8th Ed.)
Solitary lesion measuring less than 5 cm. (from AJCC 8th Ed.)
Solitary lesion measuring 5 cm or more. (from AJCC 8th Ed.)
Regional skin involvement: multiple lesions limited to one body region or two contiguous body regions. (from AJCC 8th Ed.)
All disease encompassing in a less than 15-cm circular area. (from AJCC 8th Ed.)
All disease encompassing in a 15-cm or more and less than 30-cm circular area. (from AJCC 8th Ed.)
All disease encompassing in a 30-cm or more circular area. (from AJCC 8th Ed.)
Generalized skin involvement. (from AJCC 8th Ed.)
A staging system for plasma cell myeloma based on the Revised International Staging System (RISS) criteria. This staging system does not apply to smoldering multiple myeloma (no AJCC staging system), monoclonal gammopathy of undetermined significance (no AJCC staging system), and Waldenstrom macroglobulinemia (no AJCC staging system). (from AJCC 8th Ed.)
Serum beta-2-microglobulin less than 3.5 mg/L and serum albumin 3.5 g/dL or more and no high-risk cytogenetics and normal LDH. High risk cytogenetics consist of one or more of the following: del17p, t(4;14), or t(14;16). (from AJCC 8th Ed.)
Serum beta-2-microglobulin 5.5 mg/L or more and high-risk cytogenetics and/or high LDH. High risk cytogenetics consist of one or more of the following: del17p, t(4;14), or t(14;16). (from AJCC 8th Ed.)
A cytogenetic abnormality that refers to the allelic loss of all or part of the short arm of chromosome 4.
A molecular abnormality indicating rearrangement of the DDIT3 gene.
A blood concentration of prostate specific antigen less than 25 ng/mL.
A subjective score of 0 on a prognostic scale that ranges from 0 to 7.
A subjective score of 1 on a prognostic scale that ranges from 0 to 7.
A subjective score of 2 on a prognostic scale that ranges from 0 to 7.
A subjective score of 3 on a prognostic scale that ranges from 0 to 7.
A subjective score of 4 on a prognostic scale that ranges from 0 to 7.
A subjective score of 5 on a prognostic scale that ranges from 0 to 7.
A subjective score of 6 on a prognostic scale that ranges from 0 to 7.
A subjective score of 7 on a prognostic scale that ranges from 0 to 7.
A proprietary antibody-drug conjugate (ADC) composed of a monoclonal antibody against human epidermal growth factor receptor 2 (HER2) site-specifically linked, via a protease cleavable linker, to an analog of dolastatin 10, Auristatin-0101, with potential antineoplastic activity. Upon administration, anti-HER2-vc0101 ADC PF-06804103 targets HER2 expressed on tumor cells. Upon binding, internalization and cleavage, Auristatin-0101 binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and apoptosis of HER2-expressing tumor cells. HER2, a tumor-associated antigen (TAA), is overexpressed on a variety of cancer cells.
An immune checkpoint inhibitor with potential immunomodulating and antineoplastic activities. Although the exact target is undisclosed, ASP8374 inhibits the activity of an immune checkpoint protein, which ultimately leads to the activation of a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells.
A personalized, peptide-based therapeutic dendritic cell (DC) vaccine consisting of autologous DCs loaded with immunogenic peptides derived from autologous cancer cells, with potential immunomodulating and antineoplastic activities. Upon leukapheresis, mature DCs are loaded with immunogenic neoantigens. Vaccination with the neoantigen-loaded autologous DC vaccine stimulates the host immune system to mount a cytotoxic T-lymphocyte (CTL) response against tumor cells expressing the neoantigens, which results in tumor cell lysis.
The besylate salt form of spebrutinib, an orally bioavailable, selective inhibitor of Bruton's agammaglobulinemia tyrosine kinase (BTK), with potential antineoplastic activity. Upon administration, spebrutinib targets and covalently binds to BTK, thereby preventing its activity. By irreversibly inhibiting BTK, administration of this agent may lead to an inhibition of B cell receptor (BCR) signaling and may inhibit cell proliferation of B-cell malignancies. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
The hydrochloride salt form of tirabrutinib, an orally available formulation containing an inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK), with potential antineoplastic activity. Upon administration, tirabrutinib covalently binds to BTK within B cells, thereby preventing B cell receptor signaling and impeding B cell development. As a result, this agent may inhibit the proliferation of B cell malignancies. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.
An inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, evobrutinib inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways, which leads to the inhibition of the growth of malignant B-cells that overexpress BTK. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B-lymphocyte development, activation, signaling, proliferation and survival.
An inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, zanubrutinib inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways, which leads to the inhibition of the growth of malignant B-cells that overexpress BTK. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B-lymphocyte development, activation, signaling, proliferation and survival.
The hydrochloride salt form of riviciclib, a flavone and cyclin dependent kinase (CDK) inhibitor with potential antineoplastic activity. Riviciclib selectively binds to and inhibits Cdk4/cyclin D1, Cdk1/cyclin B and Cdk9/cyclin T1, serine/threonine kinases that play key roles in the regulation of the cell cycle and cellular proliferation. Inhibition of these kinases leads to cell cycle arrest during the G1/S transition, thereby leading to an induction of apoptosis, and inhibition of tumor cell proliferation.
A cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. Upon administration, voruciclib selectively inhibits cyclin-dependent kinase 4 (CDK4) and 6 (CDK6). This inhibits retinoblastoma (Rb) protein phosphorylation early in the G1 phase, which prevents CDK-mediated G1-S phase transition and leads to cell cycle arrest. This suppresses DNA replication and decreases tumor cell proliferation. CDK4 and 6 are serine/threonine kinases that are upregulated in many tumor cell types and play a key role in the regulation of cell cycle progression.
An orally available MDM2 (murine double minute 2) antagonist with potential antineoplastic activity. Upon oral administration, milademetan binds to, and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this MDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This results in the restoration of p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger protein and a negative regulator of the p53 pathway, is overexpressed in cancer cells; it has been implicated in cancer cell proliferation and survival.
The monophosphate form of PF-04217903, an orally bioavailabe, small-molecule tyrosine kinase inhibitor with potential antineoplastic activity. MET tyrosine kinase inhibitor PF-04217903 selectively binds to and inhibits c-Met, disrupting the c-Met signaling pathway, which may result in the inhibition of tumor cell growth, migration and invasion of tumor cells, and the induction of death in tumor cells expressing c-Met. The receptor tyrosine kinase c-Met, also known as hepatocyte growth factor (HGF) receptor, is overexpressed or mutated in many tumor cell types, playing an important role in tumor cell proliferation, survival, invasion, and metastasis and angiogenesis.
A recombinant fusion protein comprised of cergutuzumab, a genetically engineered human immunoglobulin G1 kappa (IgG1k) monoclonal antibody directed against carcinoembryonic antigen (CEA, CEACAM5, CD66e), linked to amunaleukin, an engineered, mutated variant form of interleukin-2 (IL-2v), with potential immunostimulating and antineoplastic activities. Upon administration of cergutuzumab amunaleukin, the cergutuzumab moiety recognizes and binds to CEA, thereby specifically targeting IL-2v to CEA-expressing tumor tissue. Subsequently, the IL-2v moiety stimulates a local immune response, which activates both natural killer (NK) cells and cytotoxic T-cells, and eventually leads to tumor cell killing. CEA is a cell surface protein that is expressed on a wide variety of cancer cells. The mutations found in IL-2v inhibit its binding to IL-2 receptor-alpha (CD25, IL2Ra), which prevents the activation of regulatory T-cells (Tregs); however, IL-2v is able to bind to and induce signaling through IL-2Rbetagamma, which allows the preferential expansion of NK cells and CD8-positive T-cells. The Fc domain of cergutuzumab is modified to prevent Fc-gamma binding and downstream effector functions.
The assumption that a person is still living.
A response indicating that an individual's malignant bowel obstruction is resolved and they are managing their care without assistance.
A response indicating that an individual is not experiencing malignant bowel obstruction symptoms but has issues with constipation.
A response indicating that an individual is experiencing malignant bowel obstruction symptoms and is receiving ambulatory care.
A response indicating that an individual is experiencing malignant bowel obstruction symptoms and is receiving care while in hospital.
A response indicating that an individual is experiencing malignant bowel obstruction symptoms and is receiving best supportive care primarily managed by a palliative care team.
A subjective score of 0 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 1 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 2 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 3 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 4 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 5 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 6 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 7 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 8 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A subjective score of 9 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
A response indicating that an individual is pretty much bedridden, rarely out of bed.
A humanized, immunoglobulin G4 (IgG4) monoclonal antibody (MAb) directed against the inhibitory receptor lymphocyte activation gene-3 protein (LAG3), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the anti-LAG3 monoclonal antibody MK-4280 binds to LAG3 expressed on tumor-infiltrating lymphocytes (TILs) and blocks its binding with major histocompatibility complex (MHC) class II molecules expressed on tumor cells. This activates antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which leads to a reduction in tumor growth. LAG3, a member of the immunoglobulin superfamily (IgSF), is expressed on various immune cells, and negatively regulates both proliferation and activation of T-cells. Its expression on TILs is associated with tumor-mediated immune suppression.
An orally available inhibitor of the protein fascin, with potential antineoplastic activity. Upon oral administration, NP-G2-044 targets and binds to fascin, thereby preventing the interaction of fascin with actin filaments, thereby preventing actin bundling and filopodia formation. By preventing actin cytoskeletal reorganization, the dynamic changes in cell shape that are necessary for tumor cell migration and invasion to occur are impaired, and tumor cell migration and metastasis are inhibited. Fascin, the main actin cross-linker protein in filopodia, is upregulated in many types of metastatic tumor cells while its expression is low or absent in normal adult epithelial cells; its expression is correlated with aggressive phenotypes, poor prognosis, and shorter survival. Filopodia, finger-like plasma membrane protrusions that are formed upon remodeling of the actin cytoskeleton, are found at a high frequency in metastatic tumor cells and their presence is correlated with tumor cell invasiveness.
A nucleotide substitution at position 1948 of the coding sequence of the FGFR3 gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 250 in the fibroblast growth factor receptor 3 protein where lysine has been replaced by glutamic acid.
A nucleotide substitution at position 2525 of the coding sequence of the FLT3 gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 842 in the receptor-type tyrosine-protein kinase FLT3 protein where tyrosine has been replaced by cysteine.
A finding indicating elevated concentrations of catecholamine metabolites in a biological sample.
A blood concentration of prostate specific antigen greater than or equal to 0.01 ng/mL.
A blood concentration of prostate specific antigen less than 150 ng/mL.
A blood concentration of prostate specific antigen between 0.1 ng/mL and 0.7 ng/mL.
A change in the nucleotide sequence of the MTOR gene that that results in constitutive activation of serine/threonine-protein kinase mTOR and its downstream signaling pathways.
A semi-quantitative microscopic finding indicating that 5 percent or more of the nucleated cells in a bone marrow sample are immature mononuclear cells of lymphoid origin.
A finding indicating elevated concentrations of the tumor antigen CA-125 in a blood serum sample.
A blood concentration of prostate specific antigen between 10 ng/mL and 15 ng/mL.
A microscopic finding indicating that 10 percent of the nucleated cells in a bone marrow sample are neoplastic plasma cells.
A blood concentration of prostate specific antigen less than 0.2 ng/mL.
A microscopic finding indicating that more than 5 percent of the nucleated cells in a peripheral leukocyte sample are neoplastic plasma cells.
A semi-quantitative microscopic finding indicating that at most 10 percent of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A change in the nucleotide sequence of the AKT1 gene that that results in constitutive activation of RAC-alpha serine/threonine-protein kinase and its downstream signaling pathways.
A change in the nucleotide sequence of the PIK3CA gene that that results in constitutive activation of phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform and its downstream signaling pathways.
A change in the nucleotide sequence of the PIK3R1 gene that that results in constitutive activation of phosphatidylinositol 3-kinase regulatory subunit alpha and its downstream signaling pathways.
A change in the nucleotide sequence of the PIK3R2 gene that that results in constitutive activation of phosphatidylinositol 3-kinase regulatory subunit beta and its downstream signaling pathways.
The presence of mutations in both alleles of the BRCA1 gene that either lead to loss of expression of the BRCA1 protein or result in the translation of an inactive BRCA1 protein.
The presence of mutations in both alleles of the BRCA2 gene that either lead to loss of expression of the BRCA2 protein or result in the translation of an inactive BRCA2 protein.
A mutation in the EZH2 gene that leads to increased histone-lysine N-methyltransferase EZH2 activity.
A change in the nucleotide sequence of the SMARCA4 gene.
A blood concentration of prostate specific antigen less than 30 ng/mL.
A blood concentration of prostate specific antigen less than or equal to 30 ng/mL.
A finding indicating an increased presence of residual disease over time.
A proprietary formulation consisting of a lipid nanoparticle encapsulating a synthetic messenger RNA (mRNA) encoding the human co-stimulatory protein tumor necrosis factor ligand superfamily member 4 (TNFSF4; OX40 Ligand; OX40L), with potential immunomodulatory and antitumor activities. Although the mechanism of action has not been completely characterized, following intratumoral injection of lipid nanoparticle encapsulated OX40L mRNA-2416, the lipid nanoparticle moiety presumably binds to the plasma membrane of nearby cells and releases the OX40L mRNA into the cell. The OX40L mRNA is then translated by the cellular protein translation machinery to produce OX40L protein, which is then expressed on the plasma membrane of the cells that internalized the OX40L mRNA. OX40L binds to and activates signaling pathways downstream of its cognate receptor tumor necrosis factor receptor superfamily member 4 (TNFRSF4; OX40), which is expressed on activated T-cells. OX40L/OX40 binding promotes increased cytokine production, which can induce proliferation of memory and effector T-lymphocytes. Altogether, this may enhance an immune response that promotes the killing of nearby tumor cells. OX40L, a cell surface glycoprotein and member of the tumor necrosis factor (TNF) ligand family, provides a co-stimulatory signal for the proliferation and survival of activated T cells.
A DNA vaccine consisting of a plasmid encoding a synthetic, full-length sequence of the tumor-associated antigen (TAA) telomerase reverse transcriptase (TERT), which was derived from the consensus sequence from humans and primates and contains two immunogenic mutations (SynCon TERT), with potential immunostimulating and antineoplastic activities. Upon intramuscular administration of INO-1401 in combination with electroporation, TERT protein is expressed and activates the immune system to mount a cytotoxic T-cell (CTL) response against telomerase-expressing tumor cells, which may result in tumor cell death. TERT is the catalytic subunit of telomerase and synthesizes telomeric DNA at the chromosome ends. Telomerase prolongs the functional lifespan of cells via the restoration and maintenance of telomere length. Abnormally activated in tumorigenesis, TERT is expressed by many types of human cancer cells, but its expression is low or non-existent in normal cells.
A grouping of lymph nodes comprising neck lymph node boundary levels I-IV.
A grouping of lymph nodes comprising neck lymph node boundary levels II-IV.
The ability of localized radiation to trigger systemic antitumor effects.
An orally available, selective small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), with potential antiproliferative and antineoplastic activities. Although the mechanism of action has not been completely determined, PRMT5 inhibitor GSK3326595 binds to the substrate recognition site of PRMT5 following oral administration and inhibits its methyltransferase activity, which decreases the levels of both monomethylated and dimethylated arginine residues in histones H2A, H3 and H4 and modulates the expression of genes involved in several cellular processes, including cell proliferation. Therefore, this agent may increase the expression of antiproliferative genes and/or decrease the expression of genes that promote cell proliferation and may lead to decreased growth of rapidly proliferating cells, including cancer cells. PRTM5, an arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA) on histones and a variety of other protein substrates, is overexpressed in several neoplasms.
The subject, who met eligibility criteria, was assigned to an arm but was not treated.
The subject, who met eligibility criteria, was assigned to an arm but received treatment not associated with any of the planned arms.
A description of the likely cause of the pathology responsible for the cardiac valve stenosis.
An electrocardiographic finding of an ectopic impulse originating from the atria or atrioventricular junction for which the site of origin cannot be determined from the surface electrocardiographic recording; there may be one or more occurrences during an electrocardiographic recording.
The base-10 logarithm of the minimum angle of resolution achieved by an individual during testing.
The minimum distance from the retina that an object remains in clear focus.
The number of letters read by the subject during an eye chart assessment.
The number of letters not able to be read by the subject during an eye chart assessment.
The number of lines not able to be read by the subject during an eye chart assessment.
Radiographic progression which has been confirmed by additional imaging showing worsening of initial progression.
Apparent radiographic progression which requires confirmation, per criteria, with additional imaging.
Persistence of one or more non-target lesion(s) without unequivocal progression following an initial apparent radiographic progression.
A congenital benign neoplasm of the kidney characterized by the presence of interlacing bundles of homogenous spindle cells with small basophilic nuclei and scant eosinophilic cytoplasm.
An orally bioavailable immune checkpoint inhibitor and antagonist of the adenosine A2A receptor (A2AR; ADORA2A), with potential immunomodulating and antineoplastic activities. Upon administration, A2AR antagonist NIR178 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This prevents tumor-released adenosine from interacting with the A2A receptors, thereby blocking the adenosine/A2AR-mediated inhibition of T-lymphocytes. This results in the proliferation and activation of T-lymphocytes, and stimulates a T-cell-mediated immune response against tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits their proliferation and activation. Adenosine is often overproduced by cancer cells and plays a key role in immunosuppression.
Medicinal products, with or without the drug under study, which have the same appearance to ensure that neither the subject nor investigator can determine which medication is being administered.
Therapeutic responses that continue beyond cessation of treatment, and sometimes, beyond a pharmaceutical product's established biological action.
An assessment from a qualified medical professional based on examination of a subject's health status.
A completion status in which a document has been signed manually or electronically by the individual who is legally responsible for that document. (HL7)
Patients who meet a clinical trial's inclusion criteria for safety analysis and efficacy evaluation.
Required or expected data that is not present, which may be due to non-completion or corruption.
Ayn measurement that is not subject to observer assessment, such as those registered by an instrument.
A clinical outcome assessment that is reported by someone other than the patient or a healthcare professional.
An indication that a study is able to add subjects.
A clinical outcome assessment in which a task is performed by a subject under the administration of a healthcare professional.
A clinical outcome assessment that is reported by someone other than the patient as if he or she is the patient.
A radioactive compound that is administered to patients for diagnostic or therapeutic purposes.
Risk that remains after risk control measures have been taken.
A noxious and unintended response to a medicinal product occurring at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, or results in a congenital anomaly/birth defect.
Risk of a serious adverse drug experience. [505-1(b) of FD&C Act (21 USC. 355-1(b)]
Status in a clinical study when a participant agrees to participate following completion of the informed consent process. NOTE: In some cases, when the prospective participant is unable to legally consent, permission to participate may be obtained from their legally-authorized representative. In some cases, enrollment requires verification of eligibility and inclusion in the analysis database. [after Clinicaltrials.gov]
The physical and mental integrity of the individuals participating in a clinical study. (ICH)
A situation that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. (ICH)
The discontinuation of a clinical trial prior to the planned end date.
A serious adverse drug experience that is not listed in the labeling of a drug, or that may be symptomatically or pathophysiologically related to an adverse drug experience identified in the labeling, but differs because of greater severity, specificity, or prevalence. [505-1(b) of FD&C Act (21 USC. 355-1(b)
An orally bioavailable, small molecule inhibitor of the Wnt signaling pathway, with potential antineoplastic activity. Upon oral administration, SM08502 inhibits the expression of genes involved in the Wnt signaling pathway through an as of yet not fully elucidated mechanism. This decreased expression of Wnt pathway-related genes prevents Wnt signaling and may inhibit proliferation of cancer cells in which the Wnt signaling pathway is overactivated. The Wnt signaling pathway is dysregulated in many cancer cell types and plays a crucial role in tumor cell proliferation.
A highly aggressive, poorly differentiated carcinoma that arises from the thoracic structures. It is characterized by mutations and rearrangement of the NUT gene. It usually presents at an advanced stage with pleuritic chest pain and pleural effusion, non-productive cough, shortness of breath, and weigh loss.
A lung tumor that arises from perivascular epithelioid cells (PECs).
A benign lung tumor that arises from perivascular epithelioid cells (PECs).
A malignant lung tumor that arises from perivascular epithelioid cells (PECs).
An analogue of naturally occurring polyamine (PA), with potential antineoplastic activity. Upon subcutaneous administration, SBP-101 displaces endogenous PAs from PA-binding sites on the cell surface, which prevents internalization of PA. This inhibits PA-dependent cell cycle processes and results in cell cycle arrest, the induction of apoptosis, and inhibition of tumor cell proliferation. PA uptake is upregulated in various tumor types and increased levels of PA leads to enhanced tumor cell growth.
Any agent that inhibits the activity of the neurokinin type 3 receptor.
Pancreatic carcinoma that does not respond to treatment.
The reemergence of B acute lymphoblastic leukemia after a period of remission.
B acute lymphoblastic leukemia that does not respond to treatment.
A proprietary agent that targets the cancer stem cell (CSC) antigen CD44, with potential antineoplastic activity. Although the mechanism of action has not been elucidated, following subcutaneous administration, CD44 targeted agent SPL-108 binds to CD44 and prevents the activation of various CD44-mediated signal transduction pathways, which may lead to reduced proliferation of CD44-expressing tumor stem cells. CD44, a transmembrane glycoprotein and hyaluronic acid receptor, is expressed in healthy tissue and overexpressed in numerous cancer cell types; it plays a key role in the proliferation, migration and survival of tumor cells.
A target lesion that has been identified by computed tomography perfusion imaging.
A monoclonal antibody targeting the human co-inhibitory molecule and immune checkpoint inhibitor T-cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT), with potential immune checkpoint inhibitory activity. Upon administration, anti-TIGIT monoclonal antibody OMP-313M32 binds to TIGIT expressed on various immune cells, including T-cells, and prevents the interaction of TIGIT with its ligands CD112 (nectin-2; poliovirus receptor related-2; PVRL2) and CD155 (poliovirus receptor; PVR; nectin-like protein 5; NECL-5). This enhances the interaction of CD112 and CD155 with the costimulatory receptor CD226 (DNAX Accessory molecule-1; DNAM-1), which is expressed on immune cells, such as natural killer (NK) cells and CD8-positive T-cells, and leads to CD226 dimerization and CD226-mediated signaling. This activates the immune system to exert a T-cell-mediated immune response against cancer cells. TIGIT, a member of the Ig super family and an immune inhibitory receptor, plays a key role in the suppression of T-cell proliferation and activation; it is involved in tumor cell immune evasion and the inhibition of antiviral immune responses.
A humanized monoclonal antibody targeting a proliferation-inducing ligand (APRIL; tumor necrosis factor ligand superfamily member 13; TNFSF13), with potential antineoplastic and immune checkpoint inhibitory activities. Following administration, anti-APRIL monoclonal antibody BION-1301 binds to APRIL and inhibits its binding to both of its receptors, B-cell maturation antigen (BCMA; tumor necrosis factor receptor superfamily member 17; TNFRSF17) and transmembrane activator and CAML Interactor (TACI; tumor necrosis factor receptor superfamily member 13B; TNFRSF13B). This inhibits the activation of both BCMA and TACI, and their downstream signaling pathways, which prevents tumor growth, tumor cell adhesion to bone marrow cells and immune suppression. Additionally, BION-1301 may reduce APRIL-induced drug resistance which occurs in some tumors. APRIL, an extracellular protein and member of the tumor necrosis factor ligand superfamily (TNFSF), is expressed by bone marrow plasma cells and myeloid cells, and overexpressed in multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and colorectal carcinoma. APRIL induces immune suppression and tumor progression through the activation of BCMA- and TACI-dependent signaling pathways.
A sarcoma arising from the arterial intima of pulmonary arteries.
A proprietary monoclonal antibody targeting an as of yet undisclosed tumor-associated antigen (TAA), with potential antineoplastic activity. Although the mechanism of action has not been elucidated presumably monoclonal antibody TRK-950 binds to a specific TAA on the cell surface of tumor cells and may induce complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). This may lead to the death of tumor cells expressing the TAA.
A very rare benign lung tumor with myoepithelial differentiation.
A proprietary orally available inhibitor of methionine aminopeptidase 2 (MetAP2), which cleaves the amino-terminal methionine residue from nascent proteins, with potential antiangiogenic and antineoplastic activities. Upon administration, MetAP2 inhibitor M8891 inhibits MetAP2 aminopeptidase activity and impairs protein synthesis, which may lead to a decrease in endothelial cell proliferation. Decreased proliferation of endothelial cells results in reductions of both angiogenesis and the growth and spread of solid tumors that are dependent on new blood vessel formation. MetAP2, a metallopeptidase, is involved in promoting protein synthesis and endothelial cell proliferation.
A change in the nucleotide sequence of the CCND1 gene.
A formulation comprised of a prodrug form of the benzothiazole derivative riluzole, with potential anti-depressant, anxiolytic and antineoplastic activities. Following oral administration, trigriluzole is converted into the active form riluzole. While the mechanism of action of riluzole is unknown, its pharmacological activities, some of which may be related to its effect, include the following: 1) an inhibitory effect on glutamate release, 2) inactivation of voltage-dependent sodium channels, and 3) interference with intracellular events that follow transmitter binding at excitatory amino acid receptors. These activities may result in myorelaxation and sedation due to the blockade of glutamatergic neurotransmission. Additionally, these activities may result in the inhibition of enzymes that are necessary for cell growth, which may decrease tumor cell growth and metastasis.
The reemergence of malignant glioma after a period of remission.
The reemergence of rhabdoid tumor after a period of remission.
Peripheral primitive neuroectodermal tumor that does not respond to treatment.
Rhabdomyosarcoma that does not respond to treatment.
A subtype of adrenoleukodystrophy (ALD) occurring in approximately 40 percent of boys with ALD, primarily affecting the cerebrum, resulting in rapidly declining neurocognitive function and in most patients, premature death.
Ewing sarcoma that does not respond to treatment.
Hepatoblastoma that does not respond to treatment.
Malignant glioma that does not respond to treatment.
Medulloblastoma that does not respond to treatment.
Osteosarcoma that does not respond to treatment.
Rhabdoid tumor that does not respond to treatment.
A humanized monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1 , PCD-1; PDCD1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-1 monoclonal antibody Sym021 binds to and inhibits PD-1 activation and its downstream signaling pathways. This may restore immune function through the activation of T-cells and cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein in the immunoglobulin superfamily (IgSF), is expressed on T-cells and functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands programmed cell death ligand 1 (PD-L1) or 2 (PD-L2). Activated PD-1 plays an important role in tumor evasion from host immunity.
An orally available inhibitor of arginase, a manganese-dependent enzyme that hydrolyzes the amino acid arginine to form ornithine and urea, with potential immunomodulating and antineoplastic activities. Upon administration, arginase inhibitor INCB001158 inhibits the breakdown of arginine by arginase, which is produced by myeloid cells, and restores arginine levels. This allows arginine to stimulate the synthesis of nitric oxide and the secretion of pro-inflammatory cytokines and chemokines, which induces the proliferation and activation of T-cells. Therefore, this agent may prevent the immunosuppressive effects of tumor-infiltrating myeloid cells and promote lymphocyte-mediated immune responses against tumor cells. Arginase is produced by neutrophils, macrophages and myeloid-derived suppressor cells (MDSC) and plays a role in inflammation-associated immunosuppression.
A microsatellite stable carcinoma that arises from the colon or rectum and has metastasized to other anatomic sites.
A microsatellite stable carcinoma that arises from the colon or rectum and has spread extensively to other anatomical sites or is no longer responding to treatment.
A carcinoma that arises from the intrahepatic or extrahepatic bile ducts and has metastasized to other anatomic sites.
A carcinoma that arises from the intrahepatic or extrahepatic bile ducts and has spread extensively to other anatomical sites or is no longer responding to treatment.
The reemergence of primary cutaneous lymphoma after a period of remission.
Primary cutaneous lymphoma that does not respond to treatment.
Alveolar rhabdomyosarcoma that does not respond to treatment.
The reemergence of alveolar rhabdomyosarcoma after a period of remission.
An anti-human epidermal growth factor receptor 2 (HER2)/anti-CD3 bispecific monoclonal antibody with potential immunostimulatory and antineoplastic activities. Anti-HER2/Anti-CD3 bispecific monoclonal antibody GBR 1302 possesses two antigen recognition sites, one for HER2, a tyrosine kinase receptor overexpressed by many cancer cell types, and one for the CD3 complex, a group of T-cell surface glycoproteins that interact with the T-cell receptor (TCR). Upon administration of GBR 1302, this bispecific monoclonal antibody simultaneously binds to both CD3-expressing T-cells and HER2-expressing cancer cells, thereby crosslinking HER2-expressing tumor cells and cytotoxic T-lymphocytes (CTLs). This may result in potent CTL-mediated lysis of HER2-expressing tumor cells. HER2 plays a key role in tumor cell proliferation and tumor vascularization.
A humanized, immunoglobulin G4 (IgG4) monoclonal antibody directed against the inhibitory receptor lymphocyte activation gene 3 protein (LAG3; LAG-3), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, the anti-LAG3 monoclonal antibody TSR-033 binds to LAG3 expressed on tumor-infiltrating lymphocytes (TILs) and blocks its binding with major histocompatibility complex (MHC) class II molecules expressed on tumor cells. This activates antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which leads to a reduction in tumor growth. LAG3, a member of the immunoglobulin superfamily (IgSF), is expressed on various immune cells, and negatively regulates both proliferation and activation of T-cells. Its expression on TILs is associated with tumor-mediated immune suppression.
An orally available, selective and covalent antagonist of estrogen receptor alpha (ERalpha; ERa; ESR1; nuclear receptor subfamily 3, group A, member 1; NR3A1), with potential antineoplastic activity. Upon oral administration, selective estrogen receptor covalent antagonist (SERCA) H3B-6545 selectively and covalently binds to a cysteine that is unique to ERalpha and is not present in other nuclear hormone receptors, thereby inhibiting the activity of ERalpha. This inhibits the growth and survival of ERalpha-expressing cancer cells. ERalpha, a nuclear hormone receptor, is often overexpressed and/or mutated in a variety of cancer cell types. It plays a key role in tumor cell proliferation and survival.
Lymphocyte-rich classical Hodgkin lymphoma that does not respond to treatment.
Thyroid gland carcinoma that does not respond to treatment.
A proprietary synthetic, aerosolized C-class CpG oligodeoxynucleotide-based (ODN) agonist of toll-like receptor 9 (TLR9), with potential immunostimulating activity. Upon inhalation, CpG ODN TLR9 agonist DV281 specifically targets, binds to and activates TLR9 expressed by plasmacytoid dendritic cells (pDCs) and B-cells. This initiates immune signaling pathways and induces a cytotoxic T-lymphocyte (CTL)-mediated immune response against antigens expressed by lung cancer cells. TLR9, a member of the TLR family, plays a fundamental role in pathogen recognition and activation of the innate immune system.
The reemergence of squamous cell carcinoma of the skin after a period of remission.
Progressive, symptomatic neurofibromatosis type 1 associated with plexiform neurofibromas that cannot be removed surgically without risk of substantial morbidity.
Disease state in which the surgical removal of a tumor is not feasible or useful.
A therapeutic cancer vaccine composed of a replication-defective, serotype 5 adenovirus (Ad5) with the viral genes early 1 (E1), early 2b (E2b), and early 3 (E3) deleted, and the human glycoprotein mucin 1 (MUC1) encoded, with potential immunostimulating and antineoplastic activities. Upon subcutaneous administration, the adenoviral MUC1 vaccine ETBX-061 expresses the MUC1 protein. The expressed MUC1 may induce a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells expressing MUC1, thereby resulting in both immune-mediated inhibition of tumor cell proliferation and tumor cell death. Deletion of the E1, E2b and E3 genes from Ad5 prevents anti-adenovirus immune responses. MUC1, a tumor-associated antigen (TAA) and type I transmembrane protein, is overexpressed in a variety of tumor types. It plays an important role in cancer progression and metastasis.
A cancer priming vaccine consisting of a proprietary version of the recombinant vaccinia viral vector, modified vaccinia Ankara-Bavarian Nordic (MVA-BN), encoding both the two human tumor-associated antigens (TAAs) carcinoembryonic antigen (CEA) and mucin-1 (MUC-1), and TRICOM, which is comprised of the three human immune-enhancing co-stimulatory molecules B7-1, ICAM-1 and LFA-3, with potential immunostimulatory and antineoplastic activities. Upon subcutaneous administration of MVA-BN-CV301, followed by multiple boosting doses of the fowlpox virus (FPV) vaccine CV301, a cytotoxic T-lymphocyte (CTL) response against CEA- and MUC-1-expressing tumor cells is activated. In addition, the CV301-dependent anti-tumor CTL response upregulates the expression of programmed cell death ligand 1 (PD-L1); therefore, when CV301 is combined with a programmed cell death 1 (PD-1) immune checkpoint inhibitor, the antitumor effect may be increased. CEA and MUC-1 are overexpressed in a variety of cancers.
An orally available inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1; IDO-1), with potential immunomodulating and antineoplastic activities. Upon administration, IDO1 inhibitor LY3381916 specifically targets and binds to IDO1, a cytosolic enzyme responsible for the oxidation of the amino acid tryptophan into the immunosuppressive metabolite kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, LY3381916 restores and promotes the proliferation and activation of various immune cells, including dendritic cells (DCs), natural killer (NK) cells, and T-lymphocytes, and causes a reduction in tumor-associated regulatory T-cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may induce a cytotoxic T-lymphocyte (CTL) response against the IDO1-expressing tumor cells, thereby inhibiting the growth of IDO1-expressing tumor cells. IDO1, overexpressed by multiple tumor cell types, plays an important role in immunosuppression. Tryptophan depletion inhibits T-lymphocyte proliferation and activation, and subsequently suppresses the immune system.
Clinical TNM staging performed following systemic therapy or radiation.
Any small molecule that inhibits the enzymatic activity of the receptor tyrosine kinase c-Met (hepatocyte growth factor receptor; HGFR).
A topical solution with potential anti-inflammatory activity. Upon topical application to the affected area, VBP-926 may help reduce paronychia. Iatrogenic paronychia is associated with chemotherapy treatment.
A semi-quantitative microscopic finding indicating that less than 15 percent of the nucleated cells in a peripheral leukocyte sample are immature mononuclear cells.
A semi-quantitative microscopic finding indicating that less than 15 percent of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A Fc-engineered human fusion protein composed of two trimers of tumor necrosis factor (ligand) superfamily, member 18 (TNFSF18; GlTRL) linked to an immunoglobulin Fc domain (GITRL-Fc), with potential immunostimulatory and antineoplastic activities. Upon administration, trimeric GITRL-Fc OMP-336B11 targets, binds to and activates its co-stimulatory surface receptor (glucocorticoid-induced tumor necrosis factor receptor (GITR; TNFRSF18) expressed on T-lymphocytes and certain tumor cell types. This activates T-lymphocytes, causes T-lymphocyte proliferation and suppresses the activity of regulatory T-cells (Treg). This promotes cytotoxic T-lymphocyte (CTL)-mediated killing of tumor cells. GITRL, a member of the tumor necrosis factor (TNF) family of ligands, functions to activate the co-stimulatory receptor GITR to enhance T-cell modulated immune responses.
An aroylindole derivative and tubulin polymerization inhibitor, with potential tubulin-inhibiting, vascular-disrupting and antineoplastic activities. Upon administration, tubulin polymerization inhibitor SCB01A binds at the colchicine binding site of tubulin and prevents its polymerization in tumor blood vessel endothelial cells and in tumor cells. This blocks the formation of the mitotic spindle and leads to both cell cycle arrest at the G2/M phase and tumor cell apoptosis. Also, this agent's effect on the tumor blood vessel endothelial cells leads to a disruption of the tumor vasculature and tumor blood flow, which deprives tumor cells of nutrients and induces tumor cell apoptosis.
An orally bioavailable dietary supplement and a formulation derived from the traditional Chinese medicine (TCM) Shen Ling Bai Zhu San, that can potentially be used to ameliorate spleen deficiency and improve symptoms of digestive disorders. Shen Ling Bai Zhu San is composed of ginseng, tuckahoe, atractylodes, baked licorice, coixenolide, Chinese yam, lotus seed, shrinkage fructus amomi, platycodon grandiflorum, white hyacinth bean, and dried orange peel. In Hou Gu Mi Xi, atractylodes and platycodon grandiflorum are removed from Shen Ling Bai Zhu San and perilla leaf is added. Upon oral administration, Hou Gu Mi Xi replenishes qi, and may improve spleen qi deficiency, gastrointestinal (GI) symptoms and GI function.
A response indicating that an individual expects to, or is expected to, live longer than six months.
An orally bioavailable, adenosine triphosphate (ATP) competitive inhibitor of polo-like kinase 1 (PLK1; PLK-1; STPK13), with potential antineoplastic activity. Upon administration, PLK1 inhibitor PCM-075 selectively binds to and inhibits PLK1, which disrupts mitosis and induces selective G2/M cell-cycle arrest followed by apoptosis in PLK1-overexpressing tumor cells. PLK1, named after the polo gene of Drosophila melanogaster, is a serine/threonine kinase that is crucial for the regulation of mitosis, and plays a key role in tumor cell proliferation. PLK1 expression is upregulated in a variety of tumor cell types and high expression is associated with increased aggressiveness and poor prognosis.
An antibody-drug conjugate (ADC) consisting of a humanized anti-CD123 (interleukin-3 (IL-3) receptor alpha chain; IL3RA) immunoglobulin G1 (IgG1) monoclonal antibody conjugated, via a cleavable linker, to a cytotoxic, DNA-alkylating payload, which is an indolino-benzodiazepine dimer containing an imine moiety, with potential antineoplastic activity. Upon administration of anti-CD123 ADC IMGN632, the antibody moiety targets the cell surface antigen CD123. Upon antibody/antigen binding, internalization, and lysosome uptake, the cytotoxic moiety is released, and covalently binds to and alkylates DNA with its imine moiety. This results in cell cycle arrest in S-phase, which leads to apoptosis and inhibition of cell growth in cells overexpressing CD123. CD123, the alpha subunit of the IL-3 receptor, regulates the proliferation, survival and differentiation of hematopoietic cells. CD123 is overexpressed on a variety of cancers.
An inducible adenoviral vector encoding human pro-inflammatory cytokine interleukin-12 (IL-12; IL12), which is under the transcriptional control of the RheoSwitch Therapeutic System (RTS) (Ad-RTS-hIL-12), with potential immunomodulating and antineoplastic activities. RTS consists of two fusion proteins: Gal4-EcR, which contains a modified ecdysone receptor (EcR) fused with the DNA binding domain of the yeast Gal4 transcription factor, and VP16-RXR, which contains a chimeric retinoid X receptor (RXR) fused with the transcription activation domain of the viral protein VP16 of herpes simplex virus type 1 (HSV1). Upon intratumoral administration of Ad-RTS-hIL-12, given in combination with the proprietary, diacylhydrazine-based activator ligand veledimex (INXN-1001), veledimex binds specifically to the EcR part of the RTS and stabilizes heterodimerization between the two fusion proteins, forming an active transcription factor, which induces the transcription of IL-12 under the control of an inducible promoter containing Gal4-binding sites. The expressed IL-12 activates the immune system by promoting the activation of natural killer cells (NK cells), inducing secretion of interferon-gamma (IFN-g) and inducing cytotoxic T-lymphocyte (CTL)-mediated responses against tumor cells, which may result in immune-mediated tumor cell lysis and inhibition of tumor cell proliferation. In the presence of veledimex, the protein heterodimer changes to a stable conformation and can bind to the inducible promoter, while without veledimex the two fusion proteins form unstable heterodimers; this allows the controlled, regulated intratumoral expression of the IL-12 gene.
A cancer vaccine composed of enveloped virus-like particles (eVLPs) containing the human cytomegalovirus (CMV) antigens glycoprotein B (gB) and phosphoprotein 65 (pp65; UL83) that are combined with the immunoadjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF), with potential immunostimulatory and antineoplastic activities. Upon intradermal administration of VBI-1901, the eVLPs are taken up by and activate immune cells, such as dendritic cells (DCs), thereby stimulating the immune system to exert a cytotoxic T-lymphocyte (CTL) immune response against CMV gB and pp65-expressing tumor cells. This may lyse and inhibit the proliferation of CMV-infected cancer cells. eVLPs, derived from viral structural proteins, stimulate the immune system and promote CTL responses. CMV gB and pp65 are expressed in certain tumor cell types, such as glioblastoma multiforme (GBM). GM-CSF stimulates the immune system and potentiates the antitumor immune response.
An Fc-bearing, humanized antibody-like protein that specifically recognizes the immune checkpoint molecules programmed cell death 1 (PD-1; PD1; PDCD1; CD279; Programmed Death 1) and lymphocyte activation gene-3 (LAG-3; LAG3; CD223), with potential T-lymphocyte immunomodulatory and antineoplastic activities. Upon administration, the anti-PD-1/anti-LAG-3 dual-affinity re-targeting (DART) protein MGD013 specifically binds to both PD-1 and LAG-3, which are both expressed on T-cells. The dual blockade of the PD-1 and LAG-3 pathways enables potent activation of a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. PD-1 and LAG-3 play key roles in suppressing T-cell activation.
Mild restlessness or increased motor activity
>ULN-3.0 x ULN if baseline was normal; 1.5-3.0 x baseline if baseline was abnormal
>ULN-2.5 x ULN if baseline was normal; 2.0-2.5 x baseline if baseline was abnormal
Asymptomatic or mild symptoms; intervention not indicated
Hemoglobin (Hgb) <LLN-10.0 g/dL; <LLN-6.2 mmol/L; <LLN-100 g/L
Inability to achieve orgasm not adversely affecting relationship
Asymptomatic valvular thickening with or without mild valvular regurgitation or stenosis by imaging
Mild pain with inflammation, erythema, or joint swelling
Asymptomatic; serologic or other evidence of autoimmune reaction, with normal organ function; intervention not indicated
Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated
>ULN-1.5 x ULN if baseline was normal; > 1.0-1.5 x baseline if baseline was abnormal
Mild odor; physician intervention not indicated; self care interventions
Mildly hypocellular or <=25% reduction from normal cellularity for age
Asymptomatic; blisters covering <10% BSA
3-5 units below LLN; for follow-up, a decrease of 3-5 units (ml/min/mm Hg) below the baseline value; asymptomatic and intervention not indicated
Levels above the upper limit of normal and below the level of myocardial infarction as defined by the manufacturer
Post-craniotomy: asymptomatic; Post-lumbar puncture: transient headache; postural care indicated
Mild sensation of cold; shivering; chattering of teeth
eGFR (estimated Glomerular Filtration Rate) or CrCl (creatinine clearance) <LLN-60 ml/min/1.73 m2 or proteinuria 2+ present; urine protein/creatinine >0.5
Mild inattention or decreased level of concentration
Microscopic hematuria; minimal increase in frequency, urgency, dysuria, or nocturia; new onset of incontinence
Fever with or without constitutional symptoms
Delay in achieving orgasm not adversely affecting relationship
One or more dental caries, not involving the root
Asymptomatic; clinical or diagnostic observations only; symptoms relieved by lubricants
Symptomatic (e.g., dry or thick saliva) without significant dietary alteration; unstimulated saliva flow >0.2 ml/min
Mild discomfort or pain associated with vaginal penetration; discomfort relieved with use of vaginal lubricants or estrogen
Awareness of receptive or expressive characteristics; not impairing ability to communicate
Asymptomatic or mild symptoms; additional medical intervention over baseline not indicated
5-10% inter-limb discrepancy in volume or circumference at point of greatest visible difference; swelling or obscuration of anatomic architecture on close inspection
Swelling or obscuration of anatomic architecture on close inspection
Target lesions covering <10% BSA and not associated with skin tenderness
Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; no change in vision
Minor with no resultant injuries; intervention not indicated
<1.0-0.75 x LLN; if abnormal, <25% decrease from baseline
Mild induration, able to move skin parallel to plane (sliding) and perpendicular to skin (pinching up)
Covering <10% of the body surface area; no intervention indicated
FEV1% (percentages of observed FEV1 and FVC related to their respective predicted values) 99-70% predicted
Mild change in gait (e.g., wide-based, limping or hobbling)
Mild nausea, early satiety and bloating, able to maintain caloric intake on regular diet
Symptomatic; perceived by patient but not evident on physical exam
Mild swelling or obscuration of anatomic architecture on close inspection
Reduction in growth velocity by 10-29% ideally measured over the period of a year
Local therapy indicated (swish and swallow)
Adults enrolled on a Monitoring Program (on a 1, 2, 4, 3, 6, and 8 kHz audiogram): Threshold shift of 15-25 dB averaged at 2 contiguous test frequencies in at least one ear; Adults not enrolled on a Monitoring Program: Subjective change in hearing in the absence of documented hearing loss; Pediatric (on a 1, 2, 3, 4, 6, and 8 kHz audiogram): Threshold shift >20 dB hearing loss (HL) (i.e., 25 dB HL or greater); sensorineural hearing loss (SNHL) above 4 kHz (i.e., 6 or 8 kHz) in at least one ear
Minimal bleeding identified on imaging study or laparoscopy; intervention not indicated
In women, increase in length, thickness or density of hair in a male distribution that the patient is able to camouflage by periodic shaving, bleaching, or removal of hair
Mild or intermittent voice change; fully understandable; self-resolves
Abnormal glucose above baseline with no medical intervention
Limited to one site (palms, soles, or axillae); self care interventions
Laboratory finding only and intervention not indicated
Increase in length, thickness or density of hair that the patient is either able to camouflage by periodic shaving or removal of hairs or is not concerned enough about the overgrowth to use any form of hair removal
Corrected serum calcium of <LLN-8.0 mg/dL; <LLN-2.0 mmol/L; Ionized calcium <LLN-1.0 mmol/L
Mild transient reaction; infusion interruption not indicated; intervention not indicated
Tenderness with or without associated symptoms (e.g., warmth, erythema, itching)
>1.2-1.5; >1-1.5 x baseline if on anticoagulation; monitoring only indicated
Minimal bleeding identified on clinical exam; intervention not indicated
Primary repair of injured organ/structure indicated
Intermittent/irregular menses for no more than 3 consecutive menstrual cycles
Mild restriction of rotation or flexion between 60-70 degrees
Stiffness; difficulty bending to the floor to pick up a very light object but able to do athletic activity
<=25% loss of ROM (range of motion); decreased ROM limiting athletic activity
Mild changes in lactation, not significantly affecting production or expression of breast milk
Endoscopic findings only; mild discomfort with normal intake
Mild symptoms; no anxiety; intervention not indicated
Mild symptoms; reduced alertness and awareness
Asymptomatic; small focal T2/FLAIR hyperintensities; involving periventricular white matter or <1/3 of susceptible areas of cerebrum +/- mild increase in subarachnoid space (SAS) and/or mild ventriculomegaly
Localized to dependent areas, no disability or functional impairment
Mild manic symptoms (e.g., elevated mood, rapid thoughts, rapid speech, decreased need for sleep)
Cosmetically and functionally insignificant hypoplasia
Asymptomatic separation of the nail bed from the nail plate or nail loss
Asymptomatic; asymmetry with slight retraction and/or thickening of the nipple areolar complex
Sperm concentration > 0 to < 15 million/ml
Mild discomfort; not interfering with oral intake
Asymptomatic clinical or diagnostic observations only; intervention not indicated
Minimal skin changes or dermatitis (e.g., erythema, edema, or hyperkeratosis) without pain
Papules and/or pustules covering <10% BSA, which may or may not be associated with symptoms of pruritus or tenderness
Nail fold edema or erythema; disruption of the cuticle
Endoscopic findings only; minimal symptoms with normal oral intake; mild pain but analgesics not indicated
Physical signs of puberty with no biochemical markers for females <8 years and males <9 years
Delivery of a liveborn infant at >34 to 37 weeks gestation
Occasional/minimal production of sputum with cough
Radiologic findings only; minimal dyspnea on exertion
Radiologic pulmonary fibrosis <25% of lung volume associated with hypoxia
Combined area of lesions covering <10% BSA
Macules/papules covering <10% BSA with or without symptoms (e.g., pruritus, burning, tightness)
Asymptomatic or mild symptoms; occasional use of nonprescription analgesics indicated
Mild pain not interfering with activity; nonprescription medication indicated
No retinal detachment and treatment not indicated
Asymptomatic, intervention not indicated; laboratory findings only
Slightly thickened saliva; slightly altered taste (e.g., metallic)
Brief partial seizure and no loss of consciousness
Asymptomatic mucosal crusting; blood-tinged secretions
Hyperpigmentation covering <10% BSA; no psychosocial impact
Hypopigmentation or depigmentation covering <10% BSA; no psychosocial impact
Asymptomatic; intervention not indicated
Snoring and nocturnal sleep arousal without apneic periods
Mild but more than usual drowsiness or sleepiness
Mild back pain; nonprescription analgesics indicated
Increased thoughts of death but no wish to kill oneself
Asymptomatic; incidental finding of SVC thrombosis
Asymptomatic; mild symptoms with no intervention indicated
Medical intervention not indicated (e.g., superficial thrombosis)
Asymptomatic; local symptomatic management
TSH increased and no intervention initiated
Asymptomatic; hypoplasia of tooth or enamel
Endoscopic findings only; minimal hemoptysis, pain, or respiratory symptoms
Partial asymptomatic obstruction on examination (e.g., visual, radiologic or endoscopic)
Mild neurologic deficit with or without imaging confirmation
Asymptomatic valvular thickening with or without mild valvular regurgitation or stenosis
Mild pain; erythema 2.5-5cm; induration/swelling 2.5-5cm; does not interfere with activity
Mild vaginal discharge (greater than baseline for patient)
Mild discomfort or pain, edema, or redness
Asymptomatic; mild vaginal shortening or narrowing
TPA administration into line with no intent for systemic therapy indicated
Mild or intermittent change from normal voice
Detectable airway noise with minimal symptoms
Observation only; topical intervention indicated
Incisional separation, intervention not indicated
Mild; non-operative intervention indicated
Oral intervention indicated (e.g., antibiotic, antifungal, or antiviral)
Moderate restlessness or increased motor activity; limiting instrumental ADL
>3.0-5.0 x ULN if baseline was normal; >3.0-5.0 x baseline if baseline was abnormal
>2.5-5.0 x ULN if baseline was normal; >2.5-5.0 x baseline if baseline was abnormal
Moderate; short term memory loss; limiting instrumental ADL
Symptomatic; medical intervention indicated; limiting instrumental ADL
Limiting instrumental ADL; outpatient operative intervention indicated
Inability to achieve orgasm adversely affecting relationship
Asymptomatic; moderate regurgitation or stenosis by imaging
Moderate pain associated with signs of inflammation, erythema, or joint swelling; limiting instrumental ADL
Blood culture positive with no signs or symptoms
Intervention initiated (including over the counter medications)
Symptomatic, decreased oral intake; change in bowel function
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL
>1.5-3.0 x ULN if baseline was normal; >1.5-3.0 x baseline if baseline was abnormal
Pronounced odor; psychosocial impact; patient seeks medical intervention
Moderately hypocellular or >25-<50% reduction from normal cellularity for age
Local infection with moderate symptoms; oral intervention indicated (e.g., antibiotic, antifungal, or antiviral)
Moderate symptoms; oral intervention indicated (e.g., antibiotic, antifungal, or antiviral)
Symptomatic (e.g., mild wheezing); endoscopic evaluation indicated; radiographic evidence of atelectasis/lobar collapse; medical management indicated (e.g., steroids, bronchodilators)
Symptomatic (e.g., rhonchi or wheezing) but without respiratory distress; medical intervention indicated (e.g., steroids, bronchodilators)
Moderate symptoms; invasive intervention not indicated
Blisters covering 10-30% BSA; painful blisters; limiting instrumental ADL
6-8 units below LLN; for follow-up, an asymptomatic decrease of >5-8 units (ml/min/mm Hg) below the baseline value; symptomatic and intervention not indicated
Localized; local intervention indicated; oral intervention indicated (e.g., antibiotic, antifungal, or antiviral)
Localized; oral intervention indicated (e.g., antibiotic, antifungal, or antiviral)
Moderate symptoms; corticosteroids indicated
Post-craniotomy: moderate symptoms; medical intervention indicated; Post-lumbar puncture: persistent moderate symptoms; blood patch indicated
Localized; local intervention indicated (e.g., topical antibiotic, antifungal, or antiviral)
Moderate pain; pain on exertion; limiting instrumental ADL; hemodynamically stable
Moderate tremor of the entire body; narcotics indicated
Symptomatic; medical intervention indicated (e.g., fat-restricted diet); paracentesis or tube drainage indicated
Moderate impairment in attention or decreased level of concentration; limiting instrumental ADL
Moderate hematuria; moderate increase in frequency, urgency, dysuria, nocturia or incontinence; urinary catheter placement or bladder irrigation indicated; limiting instrumental ADL
Hypotension responding to fluids; hypoxia responding to <40% O2
Delay in achieving orgasm adversely affecting relationship
Moderate and acute confusional state; limiting instrumental ADL
Sedation; slow response to stimuli; limiting instrumental ADL
Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema
Oral intervention indicated (e.g., antibiotic, antifungal)
Moderate symptoms; oral intake alterations (e.g., copious water, other lubricants, diet limited to purees and/or soft, moist foods); unstimulated saliva 0.1 to 0.2 ml/min
Moderate symptoms; medical intervention indicated (e.g., oral antibiotics)
Moderate impairment of articulation or slurred speech
Moderate sensory alteration; limiting instrumental ADL
Altered taste with change in diet (e.g., oral supplements); noxious or unpleasant taste; loss of taste
Moderate discomfort or pain associated with vaginal penetration; discomfort or pain partially relieved with use of vaginal lubricants or estrogen
Moderate receptive or expressive characteristics; impairing ability to communicate spontaneously
Moderate; topical or oral intervention indicated; additional medical intervention over baseline indicated
>10-30% inter-limb discrepancy in volume or circumference at point of greatest visible difference; readily apparent obscuration of anatomic architecture; obliteration of skin folds; readily apparent deviation from normal anatomic contour; limiting instrumental ADL
Readily apparent obscuration of anatomic architecture; obliteration of skin folds; readily apparent deviation from normal anatomic contour; limiting instrumental ADL
Resting ejection fraction (EF) 50-40%; 10-19% drop from baseline
Passage of >3 unformed stools per 24 hrs or duration of illness >48 hrs; moderate abdominal pain; oral intervention indicated (e.g., antibiotic, antifungal, or antiviral)
Moderate symptoms; medical intervention indicated (e.g., nasal packing, cauterization; topical vasoconstrictors)
Target lesions covering 10-30% BSA and associated with skin tenderness
Erythema covering >90% BSA without associated symptoms; limiting instrumental ADL
Local intervention indicated (e.g., oral antibiotic, antifungal, antiviral)
Unilateral paresis without double vision
Moderate involuntary movements; limiting instrumental ADL
Moderate; minimal, local or noninvasive intervention indicated; limiting instrumental ADL; best corrected visual acuity 20/40 and better or 3 lines or less decreased vision from known baseline
Symptomatic; nonoperative intervention indicated; limiting instrumental ADL
Symptomatic; noninvasive intervention indicated
Covering 10-30% BSA and associated with erythema or tenderness; limiting instrumental ADL
<10% percentile of weight for gestational age
<0.75-0.5 x LLN; if abnormal, 25-<50% decrease from baseline
Moderate induration, able to slide skin, unable to pinch skin; limiting instrumental ADL
Covering 10-30% of the body surface area; topical intervention initiated
Moderate change in gait (e.g., wide-based, limping or hobbling); assistive device indicated; limiting instrumental ADL
Symptomatic; altered GI function; medical intervention indicated; limiting instrumental ADL
Superficial necrosis; intervention not indicated
Moderate symptoms; able to maintain nutrition with dietary and lifestyle modifications; may need pharmacologic intervention
Interfering with instrumental ADLs; oral therapy initiated
Symptomatic; evident on physical exam; limiting instrumental ADL
Readily apparent obscuration of anatomic architecture; obliteration of skin folds; readily apparent deviation from normal anatomic contour
Moderate pain interfering with oral intake
Symptomatic; dietary modification or oral agent indicated
>= +2 SD (standard deviation) above mid parental height or target height
Reduction in growth velocity by 30-49% ideally measured over the period of a year or 0-49% reduction in growth from the baseline growth curve
Adults enrolled on a Monitoring Program (on a 1, 2, 3, 4, 6, and 8 kHz audiogram): Threshold shift of >25 dB averaged at 2 contiguous test frequencies in at least one ear; Adults not enrolled on a Monitoring Program: Hearing loss with hearing aid or intervention not indicated; limiting instrumental ADL; Pediatric (on a 1, 2, 3, 4, 6, and 8 kHz audiogram): Threshold shift >20 dB at 4 kHz in at least one ear
Moderate bleeding; medical intervention indicated
Symptomatic; urinary catheter or bladder irrigation indicated; limiting instrumental ADL
Moderate symptoms; medical intervention indicated; limiting instrumental ADL
Hairline fracture; mild pain; limiting instrumental ADL; non-operative intervention indicated
In women, increase in length, thickness or density of hair in a male distribution that requires daily shaving or consistent destructive means of hair removal to camouflage; associated with psychosocial impact
Moderate or persistent voice changes; may require occasional repetition but understandable on telephone; medical evaluation indicated
Corrected serum calcium of >11.5-12.5 mg/dL; >2.9-3.1 mmol/L; Ionized calcium >1.5-1.6 mmol/L; symptomatic
Change in daily management from baseline for a diabetic; oral antiglycemic agent initiated; workup for diabetes
Involving >1 site; patient seeks medical intervention; associated with psychosocial impact
Symptomatic; thyroid suppression therapy indicated; limiting instrumental ADL
Increase in length, thickness or density of hair at least on the usual exposed areas of the body [face (not limited to beard/moustache area) plus/minus arms] that requires frequent shaving or use of destructive means of hair removal to camouflage; associated with psychosocial impact
Corrected serum calcium of <8.0-7.0 mg/dL; <2.0-1.75 mmol/L; Ionized calcium <1.0-0.9 mmol/L; symptomatic
Symptomatic with <LLN-3.0 mmol/L; intervention indicated
Symptomatic; thyroid replacement indicated; limiting instrumental ADL
Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for <=24 hrs
Erythema with associated symptoms (e.g., edema, pain, induration, phlebitis)
>1.5-2.5; >1.5-2.5 x baseline if on anticoagulation; dose adjustment indicated
Partial resection of injured organ/structure indicated
Intermittent/irregular menses for more than 3 consecutive menstrual cycles
Moderate; limiting instrumental ADL; increased attention indicated
Localized; local intervention indicated; oral intervention indicated (e.g., antibiotic, antifungal, or antiviral); needle aspiration indicated (single or multiple)
Rotation <60 degrees to right or left; <60 degrees of flexion
Pain with range of motion (ROM) in lumbar spine; requires a reaching aid to pick up a very light object from the floor
>25-50% decrease in ROM; limiting instrumental ADL
Moderate accentuation; limiting instrumental ADL
Changes in lactation, significantly affecting breast production or expression of breast milk
Symptomatic; medical intervention indicated (e.g., dexamethasone, epinephrine, antihistamines)
Moderate sore throat; analgesics indicated
Moderate pain, analgesics indicated; altered oral intake; limiting instrumental ADL
Symptomatic (e.g., noisy airway breathing), no respiratory distress; medical intervention indicated (e.g., steroids); limiting instrumental ADL
Moderate symptoms; mild anxiety, but no dyspnea; short duration of observation and/or anxiolytic indicated; limiting instrumental ADL
Transient episode; intervention not indicated
Moderate symptoms; focal T2/FLAIR hyperintensities, involving periventricular white matter extending into centrum semiovale or involving 1/3 to 2/3 of susceptible areas of cerebrum +/- moderate increase in SAS and/or moderate ventriculomegaly
Decrease in sexual interest adversely affecting relationship
>1.5-2.0 x ULN; >2.0-5.0 x ULN and asymptomatic
Covering 10-30% BSA and associated tenderness; limiting instrumental ADL
Moderate localized edema and intervention indicated; limiting instrumental ADL
Marked discoloration; leathery skin texture; papillary formation; limiting instrumental ADL
Uneasiness or lack of well being limiting instrumental ADL
Moderate manic symptoms (e.g., relationship and work difficulties; poor hygiene)
Moderate symptoms; medical intervention indicated (e.g., hormones)
Serous otitis, medical intervention indicated
Moderate pain or ulcer that does not interfere with oral intake; modified diet indicated
Deformity, hypoplasia, or asymmetry able to be remediated by prosthesis (e.g., shoe insert) or covered by clothing
Asymptomatic and cardiac enzymes minimally abnormal and no evidence of ischemic ECG changes
Moderate neck edema; slight obliteration of anatomic landmarks; limiting instrumental ADL
Symptomatic; asymmetry of nipple areolar complex with moderate retraction and/or thickening of the nipple areolar complex
Moderate decrease in visual acuity (best corrected visual acuity 20/40 and better or 3 lines or less decreased vision from known baseline)
Moderate pain; interfering with oral intake
Moderate pain; altered oral intake; non-narcotics initiated; topical analgesics initiated
Symptomatic; medical intervention indicated (e.g., topical agents); limiting instrumental ADL
Symptomatic; medical intervention indicated (e.g., analgesics or bisphosphonates); limiting instrumental ADL
Symptomatic and intervention not indicated
Skin changes (e.g., peeling, blisters, bleeding, fissures, edema, or hyperkeratosis) with pain; limiting instrumental ADL
Increase in stool frequency, bulk, or odor; steatorrhea
Papules and/or pustules covering 10-30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; associated with psychosocial impact; limiting instrumental ADL; papules and/or pustules covering > 30% BSA with or without mild symptoms
Local intervention indicated; oral intervention indicated (e.g., antibiotic, antifungal, antiviral); nail fold edema or erythema with pain; associated with discharge or nail plate separation; limiting instrumental ADL
Symptomatic, not interfering with bladder, bowel, or vaginal function; limiting instrumental ADL
Asymptomatic effusion size small to moderate
Indurated or pitting edema; topical intervention indicated
Brief (<24 hrs) episode of ischemia managed medically and without permanent deficit
Symptomatic; intervention indicated (e.g., diuretics or therapeutic thoracentesis)
Moderate bleeding requiring transfusion < 2 units (10 cc/kg for pediatrics) of pRBCs
Extubated within 24-72 hrs postoperatively
Delivery of a liveborn infant at >28 to 34 weeks gestation
Moderate sputum production; limiting instrumental ADL
Recurrent after manual reduction; local irritation or stool leakage; difficulty to fit appliance; limiting instrumental ADL
Local care or maintenance; minor revision indicated
Moderate psychotic symptoms (e.g., disorganized speech; impaired reality testing)
Moderate dyspnea on exertion; medical intervention indicated; limiting instrumental ADL
Evidence of pulmonary hypertension; radiographic pulmonary fibrosis 25-50% associated with hypoxia
Combined area of lesions covering 10-30% BSA; bleeding with trauma
Macules/papules covering 10-30% BSA with or without symptoms (e.g., pruritus, burning, tightness); limiting instrumental ADL; rash covering > 30% BSA with or without mild symptoms
Symptomatic; oral antiemetics indicated; around the clock nonprescription analgesics or any oral narcotic analgesics indicated
Moderate pain; limiting instrumental ADL; prescription medication indicated
No retinal detachment and treatment indicated
Retinal vascular disorder without neovascularization
Moderate; minimal, local or noninvasive intervention indicated; limiting instrumental ADL
Thick, ropy, sticky saliva; markedly altered taste; alteration in diet indicated; secretion-induced symptoms; limiting instrumental ADL
>20-45 degrees; visible by forward flexion; limiting instrumental ADL
Moderate arthralgia; fever, rash, urticaria, antihistamines indicated
Local infection with moderate symptoms; oral intervention indicated; limiting age-appropriate instrumental ADL
Symptomatic stenosis or edema/narrowing interfering with airflow; limiting instrumental ADL
Blood bilirubin 2-5 mg/dL; minor interventions required (i.e., blood product, diuretic, oxygen)
Hyperpigmentation covering >10% BSA; associated psychosocial impact
Hypopigmentation or depigmentation covering >10% BSA; associated psychosocial impact
Combined area of ulcers 1-2 cm; partial thickness skin loss involving skin or subcutaneous fat
Moderate apnea and oxygen desaturation; excessive daytime sleepiness; medical evaluation indicated; limiting instrumental ADL
Moderate sedation; limiting instrumental ADL
Moderate increase in muscle tone and increase in resistance through range of motion
Moderate back pain; prescription analgesics indicated; limiting instrumental ADL
Symptomatic; IV fluids indicated <24 hrs; manual dilation at bedside
Mild to moderate neurologic deficit; limiting instrumental ADL
Moderate; minimal, local or noninvasive intervention indicated
Suicidal ideation with no specific plan or intent
Symptomatic; medical intervention indicated (e.g., anticoagulation, radiation or chemotherapy)
Ankle reflex absent; other reflexes reduced
Symptomatic but not interfering with sexual function; intervention not indicated; limiting instrumental ADL
Oral intervention indicated (e.g., antifungal)
Impairment correctable with oral surgery
Moderate neurologic deficit with or without imaging confirmation
Moderate length discrepancy 2-5 cm; shoe lift indicated; limiting instrumental ADL
Limiting instrumental ADL; medical management indicated
Symptomatic but no hydronephrosis, sepsis, or renal dysfunction; urethral dilation, urinary or suprapubic catheter indicated
Symptomatic; dilation or endoscopic repair or stent placement indicated
Symptomatic but no hydronephrosis, sepsis, or renal dysfunction; dilation or endoscopic repair or stent placement indicated
Moderate pain; Erythema 5.1-10 cm; Induration/swelling 5.1-10 cm; lipodystrophy; limiting instrumental ADL
Localized ulceration; generalized lymph node enlargement
Moderate to heavy vaginal discharge; use of perineal pad or tampon indicated
Moderate discomfort or pain, edema, or redness; limiting instrumental ADL
Vaginal narrowing and/or shortening not interfering with physical examination
Device dislodgement, blockage, leak, or malposition; device replacement indicated
Symptomatic (e.g., claudication); repair or revision not indicated
<75-50% of predicted value; limiting instrumental ADL
Moderate or persistent change from normal voice; still understandable
Incisional separation, local care (e.g., suturing) or medical intervention indicated (e.g., analgesic)
Severe discomfort; limiting self care ADL
IV antibiotic, antifungal, or antiviral intervention indicated; invasive intervention indicated
Severe restlessness or increased motor activity; limiting self care ADL
>5.0-20.0 x ULN if baseline was normal; >5.0-20.0 x baseline if baseline was abnormal
Bronchospasm; hospitalization indicated for clinical sequelae; intravenous intervention indicated
Severe; long term memory loss; limiting self care ADL
TPN or hospitalization indicated; invasive intervention indicated
Symptomatic and severely altered GI function; non-emergent operative intervention indicated; TPN or hospitalization indicated
Symptomatic bronchospasm, with or without urticaria; parenteral intervention indicated; allergy-related edema/angioedema; hypotension
Hgb <8.0 g/dL; <4.9 mmol/L; <80 g/L; transfusion indicated
Limiting self care ADL; elective operative intervention indicated requiring hospitalization
Symptomatic; severe regurgitation or stenosis by imaging; symptoms controlled with medical intervention
Medical intervention indicated; operative intervention indicated
Severe pain associated with signs of inflammation, erythema, or joint swelling; irreversible joint damage; limiting self care ADL
Autoimmune reactions involving major organ (e.g., colitis, anemia, myocarditis, kidney)
Severely altered GI function; invasive intervention indicated
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of existing hospitalization indicated; limiting self care ADL
>3.0-10.0 x ULN if baseline was normal; >3.0-10.0 x baseline if baseline was abnormal
Severely hypocellular or >50-<=75% reduction cellularity from normal for age
Asymmetry >1/3 of breast volume; severe atrophy
IV antibiotic, antifungal, or antiviral intervention indicated; severe infection; axillary adenitis
Shortness of breath with stridor; endoscopic intervention indicated (e.g., laser, stent placement)
Hospitalization; invasive intervention indicated
Limiting self care ADL; supplemental oxygen indicated
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of existing hospitalization indicated; asterixis; mild encephalopathy
Blisters covering >30% BSA; limiting self care ADL
Asymptomatic decrease of >8 units drop; >5 units drop along with the presence of pulmonary symptoms (e.g., >Grade 2 hypoxia or >Grade 2 dyspnea); intervention indicated
Levels consistent with myocardial infarction as defined by the manufacturer
Severe symptoms; medical intervention indicated
Pain at rest; limiting self care ADL; cardiac catheterization; new onset cardiac chest pain; unstable angina
Severe or prolonged, not responsive to narcotics
Hospitalization indicated; invasive intervention indicated
Severely altered GI function; tube feeding or hospitalization indicated; elective operative intervention indicated
Severe impairment in attention or decreased level of concentration; limiting self care ADL
Corneal ulcer without perforation in the affected eye
Severe symptoms, medical intervention or hospitalization indicated
Gross hematuria; transfusion, IV medications, or hospitalization indicated; elective invasive intervention indicated
Hypotension managed with one pressor; hypoxia requiring >= 40% O2
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of existing hospitalization indicated; IV intervention indicated
Severe and acute confusional state; limiting self care ADL; urgent intervention indicated; new onset
Severe delusional symptoms; hospitalization not indicated; new onset
Dental caries resulting in pulpitis or periapical abscess or resulting in tooth loss
Moist desquamation in areas other than skin folds and creases; bleeding induced by minor trauma or abrasion
Inability to adequately aliment orally; tube feeding or TPN indicated; unstimulated saliva <0.1 ml/min
Severely altered GI function; TPN indicated; elective invasive intervention indicated; limiting self care ADL
Severe impairment of articulation or slurred speech
Severe sensory alteration; limiting self care ADL
Severe discomfort or pain associated with vaginal penetration; discomfort or pain unrelieved by vaginal lubricants or estrogen
Severe symptoms; operative intervention indicated
Severe receptive or expressive characteristics; impairing ability to read, write or communicate intelligibly
Severe or medically significant but not immediately life-threatening; IV intervention indicated
>30% inter-limb discrepancy in volume; gross deviation from normal anatomic contour; limiting self care ADL
Gross deviation from normal anatomic contour; limiting self care ADL
Resting ejection fraction (EF) 39-20%; >=20% drop from baseline
Average QTc >= 501 ms; >60 ms change from baseline
IV antibiotic, antifungal, or antiviral intervention indicated; severe changes in mental status; self-limited seizure activity; focal neurologic abnormalities
Systemic intervention; hospitalization indicated
IV antibiotic, antifungal, or antiviral intervention indicated; invasive intervention indicated; profuse watery diarrhea with signs of hypovolemia; bloody diarrhea; fever; severe abdominal pain; hospitalization indicated
Severe or persistent abdominal pain; fever; ileus; peritoneal signs
Transfusion; invasive intervention indicated (e.g., hemostasis of bleeding site)
Target lesions covering >30% BSA and associated with oral or genital erosions
Erythema covering >90% BSA with associated symptoms (e.g., pruritus or tenderness); limiting self care ADL
Inability to aliment adequately by GI tract; invasive intervention indicated
Bilateral paresis or unilateral paresis causing double vision in peripheral gaze, but not in central gaze
Severe involuntary movements or torticollis; limiting self care ADL
Severe or medically significant but not immediately sight-threatening; limiting self care ADL; decrease in visual acuity (best corrected visual acuity worse than 20/40 or more than 3 lines of decreased vision from known baseline, up to 20/200)
Limiting self care ADL; operative intervention indicated
Covering >30% BSA; associated with erythema or tenderness; limiting self-care ADL
<5% percentile of weight for gestational age
>40.0 degrees C (>104.0 degrees F) for <=24 hrs
<0.5-0.25 x LLN; if abnormal, 50-<75% decrease from baseline
Severe induration; unable to slide or pinch skin; limiting joint or orifice movement (e.g., mouth, anus); limiting self care ADL
Symptomatic, associated with hypotension and/or tachycardia; limiting self care ADL
>30% BSA; systemic intervention indicated
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of existing hospitalization indicated
Severe symptoms; hospitalization indicated; elective operative intervention indicated
Weight loss >=20% from baseline; tube feeding or TPN indicated; elective operative intervention indicated
Interferes with self care ADL; intravenous therapy indicated; skin breakdown
Lymphorrhea; gross deviation from normal anatomic contour; limiting self care ADL
Severe pain; inability to aliment orally
Reduction in growth velocity of >=50% ideally measured over the period of a year
Severe hallucinations; hospitalization not indicated
Adults enrolled on a Monitoring Program (on a 1, 2, 3, 4, 6, and 8 kHz audiogram): Threshold shift of >25 dB averaged at 3 contiguous test frequencies in at least one ear; therapeutic intervention indicated; Adults not enrolled on a Monitoring Program: Hearing loss with hearing aid or intervention indicated; limiting self care ADL; Pediatric (on a 1, 2, 3, 4, 6, and 8 kHz audiogram): Hearing loss sufficient to indicate therapeutic intervention, including hearing aids; threshold shift >20 dB at 2 to < 4 kHz in at least one ear
Symptoms at rest or with minimal activity or exertion; hospitalization; new onset of symptoms
Transfusion indicated; invasive intervention indicated
Gross hematuria; transfusion, IV medications, or hospitalization indicated; elective invasive intervention indicated; limiting self care ADL
Laboratory findings with clinical consequences (e.g., renal insufficiency, petechiae)
Asterixis; mild encephalopathy; drug-induced liver injury (DILI); limiting self care ADL
Symptomatic liver dysfunction; fibrosis by biopsy; compensated cirrhosis; hospitalization or prolongation of existing hospitalization indicated
Severe symptoms; interfering with sleep; limiting self care ADL
Severe pain; hospitalization or intervention indicated for pain control (e.g., traction); operative intervention indicated
Severe voice changes including predominantly whispered speech
Corrected serum calcium of >12.5-13.5 mg/dL; >3.1-3.4 mmol/L; Ionized calcium >1.6-1.8 mmol/L; hospitalization indicated
Insulin therapy initiated; hospitalization indicated
Associated with electrolyte/hemodynamic imbalance
>6.0-7.0 mmol/L; hospitalization indicated
>155-160 mmol/L; hospitalization indicated
Corrected serum calcium of <7.0-6.0 mg/dL; <1.75-1.5 mmol/L; Ionized calcium <0.9-0.8 mmol/L; hospitalization indicated
Increase in body temperature; limiting self care ADL
<3.0-2.5 mmol/L; hospitalization indicated
125-129 mmol/L symptomatic; 120-124 mmol/L regardless of symptoms
Severe symptoms; medical intervention or hospitalization indicated
Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae
Ulceration or necrosis; severe tissue damage; operative intervention indicated
Severe symptoms; limiting self care ADL (e.g., transient cerebral ischemia); repair or revision indicated
Symptomatic limiting self care ADL; repair or revision indicated
>2.5; >2.5 x baseline if on anticoagulation; bleeding
Severe symptoms; IV fluids, tube feeding, or TPN indicated >=24 hrs; elective operative intervention indicated
Ventriculostomy, ICP monitoring, intraventricular thrombolysis, or invasive intervention indicated; hospitalization
Complete resection or reconstruction of injured organ/structure indicated; limiting self care ADL
Complete resection or reconstruction of injured organ/structure indicated; limiting self care ADL (e.g., impaired hearing; impaired balance)
Postoperative invasive intervention indicated; hospitalization
Resection or reconstruction of injured organ/structure indicated; limiting self care ADL
Severe abnormal or excessive response; limiting self care ADL; inconsolable; medical or psychiatric intervention indicated
Arthroscopic intervention indicated (e.g., drainage) or arthrotomy (e.g., open surgical drainage)
Ankylosed/fused over multiple segments with no C-spine rotation
<50% lumbar spine flexion; associated with symptoms of ankylosis or fused over multiple segments with no L-spine flexion (e.g., unable to reach to floor to pick up a very light object)
>50% decrease in ROM; limiting self care ADL
Severe accentuation; operative intervention indicated; limiting self care ADL
Stridor; respiratory distress; hospitalization indicated
Severe throat pain; endoscopic intervention indicated
Severe pain; severely altered eating/swallowing; medical intervention indicated
Limiting self care ADL; stridor; endoscopic intervention indicated (e.g., stent, laser)
Severe symptoms; dyspnea and swallowing difficulty; limiting self care ADL
Recurrent episodes; noninvasive intervention indicated (e.g., breathing technique, pressure point massage)
Severe symptoms; extensive T2/FLAIR hyperintensities, involving periventricular white matter involving 2/3 or more of susceptible areas of cerebrum +/- moderate to severe increase in SAS and/or moderate to severe ventriculomegaly
>2.0-5.0 x ULN with signs or symptoms; >5.0 x ULN and asymptomatic
Covering >30% BSA and associated tenderness and narcotics or NSAIDs indicated; lipohypertrophy; limiting self care ADL
Severe localized edema and intervention indicated; limiting self care ADL
Uneasiness or lack of well being limiting self-care ADL
Severe manic symptoms (e.g., hypomania; major sexual or financial indiscretions); hospitalization not indicated; new onset
IV antibiotic, antifungal, or antiviral intervention indicated; invasive intervention indicated; focal neurologic deficit
Severe; transfusion indicated; operative intervention indicated (e.g., hysterectomy)
Mastoiditis; necrosis of canal soft tissue or bone
Severe pain; interfering with oral intake
Shock with azotemia and acid-base disturbances; significant coagulation abnormalities
Severe symptoms; cardiac enzymes abnormal; hemodynamically stable; ECG changes consistent with infarction
Associated with bloody nasal discharge or epistaxis
Generalized neck edema (e.g., difficulty in turning neck); limiting self care ADL
Not immediately life-threatening; hospitalization or prolongation of existing hospitalization indicated; limiting self care ADL
Marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or more than 3 lines of decreased vision from known baseline, up to 20/200)
Disabling pain; tube feeding or TPN indicated
Severe pain; severely altered eating/swallowing; narcotics initiated; requires parenteral nutrition
Severe skin changes (e.g., peeling, blisters, bleeding, fissures, edema, or hyperkeratosis) with pain; limiting self care ADL
Symptomatic with marked decrease in visual acuity (best corrected visual acuity worse than 20/40 or more than 3 lines of decreased vision from known baseline, up to 20/200)
Papules and/or pustules covering >30% BSA with moderate or severe symptoms; limiting self-care ADL; IV antibiotics indicated
Operative intervention indicated; IV antibiotics indicated; limiting self care ADL
Edema associated with visual disturbance; increased intraocular pressure, glaucoma or retinal hemorrhage; optic neuritis; diuretics indicated; operative intervention indicated
Prolonged (>=24 hrs) or recurring symptoms and/or invasive intervention indicated
Severe personality change; hospitalization not indicated
Severe pain; unable to adequately aliment or hydrate orally; limiting self care ADL
Symptomatic with respiratory distress and hypoxia; operative intervention including chest tube or pleurodesis indicated
Severe symptoms; limiting self care ADL; oxygen indicated
Reversal/retrograde portal vein flow; associated with varices and/or ascites
Transfusion indicated of >=2 units (10 cc/kg for pediatrics) pRBCs; invasive intervention indicated; hospitalization
Extubated >72 hrs postoperatively, but before tracheostomy indicated
Delivery of a liveborn infant at 24 to 28 weeks gestation
Persistent or copious production of sputum; limiting self care ADL
Severe symptoms; elective operative intervention indicated; limiting self care ADL
Dysfunctional stoma; elective operative intervention or major stomal revision indicated
Severe or medically significant but not immediately life-threatening; limiting self care ADL
Severe psychotic symptoms (e.g., paranoid, extreme disorganization); hospitalization not indicated; new onset
Severe dyspnea or dyspnea at rest; oxygen indicated; limiting self care ADL
Severe hypoxia; evidence of right-sided heart failure; radiographic pulmonary fibrosis >50-75%
Combined area of lesions covering >30% BSA; spontaneous bleeding
Papules and/or pustules covering >30% BSA with moderate or severe symptoms; limiting self-care ADL; associated with local superinfection with oral antibiotics indicated
Macules/papules covering >30% BSA with moderate or severe symptoms; limiting self care ADL
Severe symptoms; medical intervention indicated (e.g., thyroplasty, vocal cord injection)
Hospitalization indicated; IV intervention (e.g., analgesics, antiemetics); elective invasive intervention indicated
Hospitalization indicated; limiting self care ADL
Retinal vascular disorder with neovascularization
Severe symptoms; limiting self care ADL; hospitalization
Acute salivary gland necrosis; severe secretion-induced symptoms (e.g., thick saliva/oral secretions or gagging); tube feeding or TPN indicated; limiting self care ADL
>45 degrees; scapular prominence in forward flexion; operative intervention indicated; limiting self care ADL
Blood culture positive with signs or symptoms; treatment indicated
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of existing hospitalization indicated; IV intervention indicated; limiting self-care ADL
Stenosis with significant nasal obstruction; limiting self care ADL
Covering >30% BSA; associated with ulceration
Combined area of ulcers >2 cm; full-thickness skin loss involving damage to or necrosis of subcutaneous tissue that may extend down to fascia
Oxygen desaturation; associated with pulmonary hypertension; medical intervention indicated; limiting self care ADL
Severe pain; interfering with oral intake; tube feeding, TPN or hospitalization indicated; limiting self care ADL
Severe pain; limiting self care ADL; limiting ability to swallow
Severe increase in muscle tone and increase in resistance through range of motion
Severe back pain; hospitalization or intervention indicated for pain control (e.g., vertebroplasty); limiting self care ADL; disability
Severely altered GI function; tube feeding, TPN or hospitalization indicated; elective operative intervention indicated
Skin sloughing covering <10% BSA with associated signs (e.g., erythema, purpura, epidermal detachment, and mucous membrane detachment)
Respiratory distress limiting self care ADL; medical intervention indicated
Severe neurologic deficit; limiting self care ADL; hospitalization
Specific plan to commit suicide without serious intent to die which may not require hospitalization
Suicide attempt or gesture without intent to die
Severe symptoms; multi-modality intervention indicated (e.g., anticoagulation, chemotherapy, radiation, stenting)
Severe symptoms; interfering with sexual function; limiting self care ADL; intervention indicated
Urgent medical intervention indicated (e.g., pulmonary embolism or intracardiac thrombus)
Maldevelopment with impairment not surgically correctable; limiting self care ADL
Severe pain; hemorrhage or respiratory symptoms; limiting self care ADL
Stridor or respiratory distress limiting self care ADL; invasive intervention indicated (e.g., stent, laser)
Non life-threatening secondary malignancy
Symptomatic; severe regurgitation or stenosis; symptoms controlled with medical intervention
Severe length discrepancy >5 cm; limiting self care ADL; operative intervention indicated
Altered organ function (e.g., hydronephrosis or renal dysfunction); invasive intervention indicated
Adult: Oliguria (<80 ml in 8 hr); Infants: < 0.5 mL/kg per hour for 24 hours; Children: < 500 mL/1.73 m2 body surface area per day
Altered organ function (e.g., sepsis or hydronephrosis, or renal dysfunction); elective operative intervention indicated
Symptomatic (e.g., hydronephrosis, or renal dysfunction); elective operative intervention indicated
Severe pain; Erythema > 10 cm; Induration/swelling > 10 cm; necrosis; limiting self care ADL
Severe vaginal dryness resulting in dyspareunia or severe discomfort
Severe discomfort or pain, edema, or redness; limiting self care ADL; small areas of mucosal ulceration
Vaginal narrowing and/or shortening interfering with the use of tampons, sexual activity or physical examination
Pulmonary embolism, deep vein or cardiac thrombosis; intervention indicated (e.g., anticoagulation, lysis, filter, invasive procedure)
<50% of predicted value; limiting self care ADL
Severe voice changes including predominantly whispered speech; may require frequent repetition or face-to-face contact for understandability; may require assistive technology
Severe respiratory symptoms limiting self care ADL; oxygen therapy or hospitalization indicated
Fascial disruption or dehiscence without evisceration; revision by operative intervention indicated
Life-threatening consequences; dialysis indicated
>20.0 x ULN if baseline was normal; >20.0 x baseline if baseline was abnormal
Life-threatening consequences; evidence of end organ damage; urgent operative intervention indicated
Life-threatening consequences; urgent intervention indicated (e.g., valve replacement, valvuloplasty)
Life-threatening consequences; hemodynamic or neurologic instability; organ damage; loss of extremity(ies)
>10.0 x ULN if baseline was normal; >10.0 x baseline if baseline was abnormal
Aplastic persistent for longer than 2 weeks
Life-threatening consequences; moderate to severe encephalopathy; coma
Blisters covering >30% BSA; associated with fluid or electrolyte abnormalities; ICU care or burn unit indicated
eGFR or CrCl <15 ml/min/1.73 m2; dialysis or renal transplant indicated
Life-threatening consequences; urgent intervention indicated; blindness
Life-threatening consequences, threats of harm to self or others; urgent intervention indicated
Life-threatening consequences; coma; urgent intervention indicated
Life-threatening consequences; skin necrosis or ulceration of full thickness dermis; spontaneous bleeding from involved site; skin graft indicated
Torsade de pointes; polymorphic ventricular tachycardia; signs/symptoms of serious arrhythmia
Target lesions covering >30% BSA; associated with fluid or electrolyte abnormalities; ICU care or burn unit indicated
Erythema covering >90% BSA with associated fluid or electrolyte abnormalities; ICU care or burn unit indicated
Bilateral paresis requiring head turning to see beyond central 60 degrees or double vision in central gaze
Sight-threatening consequences; urgent intervention indicated; best corrected visual acuity of 20/200 or worse in the affected eye
Life-threatening consequences; urgent intervention indicated; enucleation
<1% percentile of weight for gestational age
>40.0 degrees C (>104.0 degrees F) for >24 hrs
<0.25 x LLN; if abnormal, 75% decrease from baseline; absolute value <50 mg/dL
Generalized; associated with signs or symptoms of impaired breathing or feeding
Life-threatening consequences; urgent intervention indicated; intubation
Adults: Decrease in hearing to profound bilateral loss (absolute threshold >80 dB HL at 2 kHz and above); nonservicable hearingPediatric: Audiologic indication for cochlear implant; > 40 dB HL (i.e., 45 dB HL or more); SNHL at 2 kHz and above
Life-threatening consequences; urgent intervention indicated; severe decompensated liver function (e.g., coagulopathy, encephalopathy, coma)
Life-threatening consequences; severe decompensated liver function (e.g., coagulopathy, encephalopathy, coma)
Life-threatening consequences; symptoms associated with neurovascular compromise
Corrected serum calcium of >13.5 mg/dL; >3.4 mmol/L; Ionized calcium >1.8 mmol/L; life-threatening consequences
>7.0 mmol/L; life-threatening consequences
>8.0 mg/dL; >3.30 mmol/L; life-threatening consequences
>160 mmol/L; life-threatening consequences
Life-threatening consequences; urgent intervention indicated (e.g., dialysis)
>1000 mg/dL; >11.4 mmol/L; life-threatening consequences
Corrected serum calcium of <6.0 mg/dL; <1.5 mmol/L; Ionized calcium <0.8 mmol/L; life-threatening consequences
<30 mg/dL; <1.7 mmol/L; life-threatening consequences; seizures
<2.5 mmol/L; life-threatening consequences
<0.7 mg/dL; <0.3 mmol/L; life-threatening consequences
<120 mmol/L; life-threatening consequences
Persistent or severe episodes associated with syncope; urgent intervention indicated (e.g., fiberoptic laryngoscopy, intubation, botox injection)
Clinical manifestations of leucostasis; urgent intervention indicated
Life-threatening consequences; extensive T2/FLAIR hyperintensities, involving periventricular white matter involving most of susceptible areas of cerebrum +/- moderate to severe increase in SAS and/or moderate to severe ventriculomegaly
Life-threatening consequences (e.g., vasopressor dependent and oliguric or anuric or ischemic colitis or lactic acidosis)
Life-threatening consequences; hemodynamically unstable
Vascular or respiratory impairment requiring urgent intervention
Life-threatening consequences; incompletely controlled medically; cardioversion indicated
Life-threatening respiratory compromise; urgent intervention indicated (e.g., tracheotomy or intubation)
Delivery of a liveborn infant at 24 weeks of gestation or less
Life-threatening consequences; hospitalization or urgent intervention indicated
Life-threatening respiratory compromise; urgent intervention or intubation with ventilatory support indicated
Life-threatening consequences (e.g., hemodynamic/pulmonary complications); intubation with ventilatory support indicated; radiographic pulmonary fibrosis >75% with severe honeycombing
Life-threatening consequences; papules and/or pustules covering any % BSA, which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive superinfection with IV antibiotics indicated
Life-threatening consequences; pressor or ventilatory support indicated
Necrosis of soft tissue or bone; urgent operative intervention indicated
Life-threatening consequences (e.g., ventilatory support, dialysis, plasmapheresis, peritoneal drainage)
Any size ulcer with extensive destruction, tissue necrosis, or damage to muscle, bone, or supporting structures with or without full thickness skin loss
Cardiovascular or neuropsychiatric symptoms; urgent operative intervention indicated
Life-threatening consequences; unable to move active or passive range of motion
Skin sloughing covering 10-30% BSA with associated signs (e.g., erythema, purpura, epidermal detachment and mucous membrane detachment)
Specific plan to commit suicide with serious intent to die which requires hospitalization
Suicide attempt with intent to die which requires hospitalization
Life-threatening consequences; urgent multi-modality intervention indicated (e.g., lysis, thrombectomy, surgery)
Life-threatening consequences with hemodynamic or neurologic instability
Life-threatening consequences, (e.g., CNS hemorrhage or thrombosis/embolism or renal failure)
Skin sloughing covering >=30% BSA with associated symptoms (e.g., erythema, purpura, or epidermal detachment)
Acute life-threatening secondary malignancy; blast crisis in leukemia
Adult: Anuria (<240 ml in 24 hr); Pediatric: No urine output over 12 hours
Life-threatening consequences; widespread areas of mucosal ulceration; urgent intervention indicated
Life-threatening consequences; symptomatic hernia with evidence of strangulation; fascial disruption with evisceration; major reconstruction flap, grafting, resection, or amputation indicated
A pegylated peptide antagonist that binds to the common gamma chain (gc; IL2RG; CD132) of the signaling receptor for the pro-inflammatory cytokines interleukin (IL)-2, IL-9, and IL-15, with potential immunomodulating and antineoplastic activities. Upon administration, IL-2/9/15 gc receptor inhibitor BNZ-1 specifically targets and binds to the IL binding site on the gc receptor and blocks IL-2, IL-9 and IL-15 binding, thereby inhibiting IL-2-, IL-9-, and IL-15-mediated signaling and downstream pathways. This may inhibit proliferation of tumor cells that are dependent on IL-2/9/15 signaling for their growth. IL-2/9/15 are upregulated in certain tumor cell types and play a key role in tumor progression and survival.
A group of conditions with overlapping signs and symptoms. It includes Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease.
A rare type A thymoma displaying atypical features (hypercellularity, increased mitotic activity, and focal necrosis).
A chromosomal abnormality where one copy of 3p14 on the short arm of chromosome 3 has been deleted.
A molecular abnormality referring to the loss of at least one copy of the RB1 gene.
A semi-quantitative microscopic finding indicating that more than 5 percent of the nucleated cells in a peripheral leukocyte sample are immature mononuclear cells.
A modulator of the E3 ubiquitin ligase complex containing cereblon (CRL4-CRBN E3 ubiquitin ligase), with potential immunomodulating and antineoplastic activities. Upon administration, cereblon E3 ubiquitin ligase modulating agent CC-92480 specifically binds to cereblon (CRBN), thereby affecting the ubiquitin E3 ligase activity, and targeting certain substrate proteins for ubiquitination. This induces proteasome-mediated degradation of certain transcription factors, some of which are transcriptional repressors in T-cells. This leads to modulation of the immune system, including activation of T-lymphocytes, and downregulation of the activity of other proteins, some of which play key roles in the proliferation of certain cancer cell types. CRBN, the substrate recognition component of the CRL4-CRBN E3 ubiquitin ligase complex, plays a key role in the ubiquitination of certain proteins.
A semi-quantitative microscopic finding indicating that 20 percent or more of the nucleated cells in a bone marrow sample are immature mononuclear cells of lymphoid origin.
A semi-quantitative microscopic finding indicating that 20 percent or more of the nucleated cells in a peripheral leukocyte sample are immature mononuclear cells of lymphoid origin.
A semi-quantitative microscopic finding indicating that 5 percent or more of the nucleated cells in a bone marrow sample are immature mononuclear cells of myeloid origin.
A semi-quantitative microscopic finding indicating that 30 percent or less of the nucleated cells in a peripheral leukocyte sample are immature mononuclear cells.
A change in the nucleotide sequence of the PTEN gene that is associated with increased risk of disease.
A change in the nucleotide sequence of the TP53 gene that is associated with increased risk of disease.
A semi-quantitative microscopic finding indicating that between 5 and 30 percent of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A highly aggressive, poorly differentiated carcinoma that arises from the mediastinum/thymus. It is characterized by mutations and rearrangement of the NUT gene.
A semi-quantitative microscopic finding indicating that between 5 and 25 percent of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A vaccine consisting of irradiated allogeneic breast cancer cells, derived from the breast cancer cell line SV-BR-1 that are transfected with the immunostimulant granulocyte-macrophage colony-stimulating factor (GM-CSF; CSF2) gene, with potential immunostimulating and antineoplastic activities. Upon intradermal administration of the allogeneic GM-CSF-secreting breast cancer vaccine SV-BR-1-GM, the genetically-modified cells secrete GM-CSF. This potentiates a tumor-specific cytotoxic T-lymphocyte (CTL) immune response against breast cancer cells.
A semi-quantitative microscopic finding indicating that between 20 and 30 percent of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A change in the nucleotide sequence of an FGFR family gene.
A very rare adenocarcinoma arising from the thymus. It is characterized by the presence of malignant polygonal cells resembling hepatocytes.
An indication that the number of months that a subject's blood concentration of prostate specific antigen took to double was six months or less.
A combination formulation containing the prodrug of netupitant, fosnetupitant, a selective neurokinin 1 receptor (NK1R; TACR1) antagonist, and the hydrochloride salt form of palonosetron, a selective serotonin (5-hydroxytrytamine; 5-HT) receptor subtype 3 (5-HT3R) antagonist, with potential antiemetic activity. Upon intravenous administration, fosnetupitant is converted by phosphatases to its active form netupitant. Netupitant competitively binds to and blocks the activity of NK1Rs in the central nervous system (CNS), by inhibiting binding of the endogenous tachykinin-derived neuropeptide substance P (SP) to NK1R. This prevents delayed emesis, which is associated with SP secretion. Palonosetron competitively blocks the interaction of 5-HT with 5-HT3Rs located on vagal afferent nerves in the chemoreceptor trigger zone (CTZ). This inhibits acute emesis associated with 5-HT secretion and subsequent 5-HT3R activation. Altogether, this results in inhibition of acute and delayed nausea and vomiting, and may prevent chemotherapy-induced nausea and vomiting (CINV).
A change in the nucleotide sequence of the ALK gene that that results in constitutive activation of both ALK tyrosine kinase receptor protein and its downstream signaling pathways.
A change in the nucleotide sequence of the ROS1 gene that that results in constitutive activation of both proto-oncogene tyrosine-protein kinase ROS and its downstream signaling pathways.
A change in the nucleotide sequence of the PIK3CG gene.
A change in the nucleotide sequence of the PIK3R5 gene.
A glioblastoma that is resistant to treatment.
An agonistic monoclonal antibody that recognizes inducible T-cell co-stimulator (ICOS; CD278), with potential immunomodulating and antineoplastic activities. Upon administration, anti-ICOS agonist monoclonal antibody BMS-986226 targets and binds to ICOS expressed on certain T-cells. This stimulates ICOS-mediated signaling, induces proliferation of ICOS-positive T-cells, enhances cytotoxic T-lymphocyte (CTL) survival and augments the CTL-mediated immune response against tumor cells. ICOS, a T-cell specific, CD28-superfamily co-stimulatory molecule and immune checkpoint protein, is normally expressed on certain activated T-cells and plays a key role in the proliferation and activation of T-cells.
An orally available ataxia telangiectasia and Rad3-related (ATR)-specific kinase inhibitor, with potential antineoplastic activity. Upon oral administration, ATR kinase inhibitor BAY1895344 selectively binds to and inhibits the activity of ATR, which prevents ATR-mediated signaling. This inhibits DNA damage checkpoint activation, disrupts DNA damage repair and induces apoptosis in ATR-overexpressing tumor cells. ATR, a serine/threonine protein kinase upregulated in a variety of cancer cell types, plays a key role in DNA repair, cell cycle progression and cell survival.
A human immunoglobulin G1 (IgG1) monoclonal antibody against the pro-inflammatory cytokine interleukin 17A (IL-17A; IL-17), with potential anti-inflammatory activity. Upon subcutaneous administration, anti-IL17A monoclonal antibody CJM112 selectively targets and binds to IL-17A, thereby neutralizing the IL-17A protein. This prevents binding of IL-17A to the IL-17 receptor (IL-17R), and inhibits IL-17A/IL-17R-mediated signaling and inflammation mediated by this pathway. IL-17A is mainly produced by inflammatory T helper 17 cells (Th17), and certain lymphocytes. IL-17A production is upregulated in many immune-mediated inflammatory diseases, such as psoriasis and multiple sclerosis (MS), and plays a key role in the development of inflammation and the immune response.
An orally available covalent inhibitor of human epidermal growth factor receptor 2 (HER2; ERBB2), with potential antineoplastic activity. Upon oral administration, HER2 inhibitor TAS0728 specifically and irreversibly binds to and inhibits the activity of HER2. This prevents HER2-mediated signaling and leads to cell death in HER2- and HER3 (ErbB3)-expressing tumor cells. HER2, a receptor tyrosine kinase mutated or overexpressed in many tumor cell types, play key roles in tumor cell proliferation and tumor vascularization. HER3 has no active kinase domain but is activated through heterodimerization with other members of the EGFR receptor family, such as HER2.
An mRNA-based individualized, therapeutic personalized cancer vaccine (PCV) targeting twenty tumor-associated antigens (TAAs) that are specifically expressed by the patient's cancer cells, with potential immunostimulatory and antineoplastic activities. The cells from the patient's tumor are analyzed, and genetic sequencing is used to identify twenty neoantigen epitopes that may elicit the strongest immune response in the patient. The sequences encoding the twenty patient-specific epitopes are transcribed and loaded onto a single mRNA molecule. Upon administration, the mRNA-based PCV mRNA-4157 is taken up and translated by antigen presenting cells (APCs). Then, the expressed epitopes are presented via major histocompatibility complex (MHC) molecules on the surface of the APCs. This leads to an induction of both cytotoxic T-lymphocyte (CTL)- and memory T-cell-dependent immune responses that specifically target and destroy the patient's cancer cells that express these neoantigens.
A humanized, Fc domain-containing, bispecific monoclonal antibody targeting human CD3, a T-cell surface antigen, and somatostatin receptor 2 (SSTR2), a tumor-associated antigen (TAA) expressed on certain cancer cells, with potential antineoplastic activity. Upon administration, anti-SSTR2/CD3 monoclonal antibody XmAb18087 binds to both T-cells and SSTR2-expressing cancer cells. The resulting cross-linkage may trigger a potent cytotoxic T-lymphocyte (CTL) response against the SSTR2-expressing cancer cells. The inclusion of an Fc domain on the antibody prolongs the half-life of the bispecific antibody.
A topical ointment composed of the water-insoluble taxane paclitaxel that has been processed to form uncoated nanoparticles, with potential antineoplastic activity. Upon topical administration of nanoparticle paclitaxel ointment SOR007 to the affected area, and following epithelial and dermal penetration, paclitaxel binds to tubulin and inhibits the disassembly of microtubules, which leads to the inhibition of cell division, thereby halting the proliferation of rapidly-dividing tumor cells. The nanoparticles in the nanoparticle paclitaxel ointment are produced through a specific proprietary submicron particle production.
A proprietary recombinant bispecific T-cell engager (BiTE) antibody composed of two single-chain variable fragments (scFv), one that is directed against a tumor-associated antigen (TAA), the epidermal growth factor receptor (EGFR) deletion-mutant form, EGFR variant III (EGFRvIII), and one that is directed against the CD3 antigen found on T-lymphocytes, with potential immunostimulating and antineoplastic activities. Upon administration of anti-EGFRvIII/CD3 BiTE antibody AMG 596, the bispecific antibody binds to both the CD3 antigen on cytotoxic T-lymphocytes (CTLs) and EGFRvIII found on EGFRvIII-expressing tumor cells. This activates and crosslinks CTLs with EGFRvIII-expressing tumor cells, which results in the CTL-mediated cell death of EGFRvIII-expressing tumor cells. EGFRvIII, a mutation in the EGFR gene where exons 2-7 have been deleted, is overexpressed by a variety of cancers, but is absent in normal, healthy cells. It plays a key role in tumor cell proliferation, tumor angiogenesis and resistance to both radio- and chemotherapy.
An orally bioavailable inhibitor of the bromodomain-containing protein 4 (BRD4), with potential antineoplastic activity. Upon oral administration, the BRD4 inhibitor PLX2853 binds to the acetylated lysine recognition motifs in the bromodomains of the BRD4 protein, thereby preventing the binding of BRD4 to acetylated lysines on histones. This disrupts chromatin remodeling and dyregulates gene expression. This may lead to the downregulation of the expression of certain growth-promoting genes, which may induce apoptosis and inhibit the proliferation of BRD4-overexpressing tumor cells. BRD4, a member of the human bromodomain and extra-terminal (BET) family of proteins, is a transcriptional regulator that is overexpressed in certain tumor cells and plays an important role in cellular proliferation.
A TNM finding about one or more characteristics of a mediastinal germ cell tumor. This is not an official UICC TNM classification. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
A TNM finding about one or more characteristics of a mediastinal germ cell tumor as they pertain to distant metastases. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor without evidence of distant metastasis. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor with distant metastasis. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
A TNM finding about one or more characteristics of a mediastinal germ cell tumor as they pertain to staging of the primary tumor. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Primary tumor cannot be assessed. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
No evidence of primary tumor. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor confined to the organ of origin (thymus and mediastinal fat). (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor confined to the organ of origin (thymus and mediastinal fat) and measuring 5 cm or less. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor confined to the organ of origin (thymus and mediastinal fat) and measuring more than 5 cm. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor infiltrating contiguous organs or accompanied by malignant effusion. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor infiltrating contiguous organs or accompanied by malignant effusion and measuring 5 cm or less. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor infiltrating contiguous organs or accompanied by malignant effusion and measuring more than 5 cm. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor invading into neighboring structures, such as pericardium, mediastinal pleura, thoracic wall, great vessels and lung. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor with pleural or pericardial dissemination. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
A TNM finding about one or more characteristics of a mediastinal germ cell tumor as they pertain to staging of regional lymph nodes. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Regional lymph nodes cannot be assessed. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor with no regional lymph node metastasis. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor with metastasis in regional lymph nodes. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor with metastasis in other intrathoracic lymph nodes excluding anterior mediastinal lymph nodes. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Mediastinal germ cell tumor with metastasis in scalene and/or supraclavicular lymph nodes. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
A term that refers to the staging of mediastinal malignant germ cell tumors according to the Pediatric Study Group staging criteria. This staging system is not an official UICC TNM classification. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Locoregional tumor, non-metastatic, complete resection. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Locoregional tumor, non-metastatic, macroscopic complete resection but microscopic residual tumor. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
Locoregional tumor, regional lymph nodes negative or positive; no distant metastasis; biopsy only or gross residual tumor after primary resection. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
An orally bioavailable inhibitor of the membrane-bound O-acyltransferase (MBOAT) porcupine (PORCN), with potential antineoplastic, protective and regenerative activities. Upon oral administration, PORCN inhibitor CGX1321 specifically targets and binds to PORCN in the endoplasmic reticulum (ER), thereby inhibiting the post-translational palmitoylation and secretion of Wnt ligands, thus preventing the activation of Wnt-mediated signaling, and inhibiting cell growth in Wnt-driven tumors. In addition, by inhibiting the secretion of Wnt ligands and preventing Wnt-mediated signaling, CGX1321 may also limit fibrosis and promote regeneration of certain tissues upon cell injury. PORCN catalyzes the palmitoylation of Wnt ligands, and plays a key role in Wnt ligand secretion. Wnt signaling is dysregulated in a variety of cancers and plays a key role in tumor cell proliferation. It also plays a key role in tissue regeneration.
A fusion protein composed of a tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptor agonist consisting of six receptor binding domains (RBDs) of TRAIL fused to the Fc-domain of a human immunoglobulin G1 (IgG1) antibody, with potential pro-apoptotic and antineoplastic activities. Upon administration of TRAIL receptor agonist ABBV-621, this fusion protein binds to TRAIL-receptors, pro-apoptotic death receptors (DRs) TRAIL-R1 (death receptor 4; DR4) and TRAIL-R2 (death receptor 5; DR5), expressed on tumor cells, thereby inducing tumor cell apoptosis. ABBV-621 is designed to maximize receptor clustering for optimal efficacy. TRAIL, a member of the TNF superfamily of cytokines, plays a key role in the induction of apoptosis through TRAIL-mediated death receptor pathways.
An angiosarcoma that has spread from its original site of growth to nearby tissues or lymph nodes.
An epithelioid hemangioendothelioma that has spread from its original site of growth to nearby tissues or lymph nodes.
An epithelioid hemangioendothelioma which has spread from its original site of growth to another anatomic site.
A bispecific monoclonal antibody against human CD3, a T-cell surface antigen, and human B-cell maturation antigen (BCMA; TNFRSF17), a tumor-associated antigen (TAA) expressed on plasma cells, with potential antineoplastic activity. Upon administration, anti-CD3/anti-BCMA bispecific monoclonal antibody PF-06863135 binds to both CD3 on T-cells and BCMA expressed on malignant plasma cells. This results in the cross-linking of T-cells and tumor cells, and induces a potent cytotoxic T-lymphocyte (CTL) response against BCMA-expressing plasma cells. BCMA, a member of the tumor necrosis factor receptor superfamily that is specifically overexpressed on malignant plasma cells, plays a key role in promoting plasma cell survival.
A malignant germ cell tumor that arises from the mediastinum. It is characterized by the presence of at least two different germ cell tumor components. The different germ cell tumor components include choriocarcinoma, embryonal carcinoma, yolk sac tumor, teratoma, and seminoma.
A monoclonal antibody (mAb) directed against human transforming growth factor beta (TGF-beta; TGFb), with potential antineoplastic activity. Upon administration, anti-TGF-beta monoclonal antibody SAR-439459 specifically targets and binds to TGF-beta, thereby preventing the activation of TGF-beta-mediated signaling pathways. This may inhibit the proliferation of tumor cells in which TGF-beta is overactivated. TGF-beta, a pro-inflammatory mediator that is mutated and/or overexpressed in a variety of cancer cell types, is involved in cancer cell proliferation and migration, and in tumor progression.
A change in the amino acid residue at position 1174 in the ALK tyrosine kinase receptor protein where phenylalanine has been replaced by leucine.
A nucleotide substitution at position 3522 of the coding sequence of the ALK gene where cytosine has been mutated to guanine.
A nucleotide substitution at position 3522 of the coding sequence of the ALK gene where cytosine has been mutated to adenine.
A nucleotide substitution at position 3520 of the coding sequence of the ALK gene where thymine has been mutated to cytosine.
A change in the amino acid residue at position 1174 in the ALK tyrosine kinase receptor protein where phenylalanine has been replaced by cysteine.
A nucleotide substitution at position 3521 of the coding sequence of the ALK gene where thymine has been mutated to guanine.
A change in the amino acid residue at position 1174 in the ALK tyrosine kinase receptor protein where phenylalanine has been replaced by valine.
A nucleotide substitution at position 3520 of the coding sequence of the ALK gene where thymine has been mutated to guanine.
A nucleotide substitution at position 3185 of the coding sequence of the ALK gene where adenine has been mutated to thymine.
A change in the amino acid residue at position 1062 in the ALK tyrosine kinase receptor protein where lysine has been replaced by methionine.
A nucleotide substitution at position 3824 of the coding sequence of the ALK gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 1275 in the ALK tyrosine kinase receptor protein where arginine has been replaced by glutamine.
A change in the amino acid residue at position 1087 in the ALK tyrosine kinase receptor protein where threonine has been replaced by isoleucine.
A change in the amino acid residue at position 1245 in the ALK tyrosine kinase receptor protein where phenylalanine has been replaced by leucine.
A nucleotide substitution at position 3735 of the coding sequence of the ALK gene where cytosine has been mutated to guanine.
A nucleotide substitution at position 3735 of the coding sequence of the ALK gene where cytosine has been mutated to adenine.
A nucleotide substitution at position 3733 of the coding sequence of the ALK gene where thymine has been mutated to cytosine.
A change in the amino acid residue at position 601 in the serine/threonine protein kinase B-raf protein where lysine has been replaced by glutamic acid.
A malignant tumor that arises from the mediastinum and is composed of myeloblasts, neutrophils and neutrophil precursors. It is the most common type of myeloid sarcoma affecting the mediastinum.
A variation in the amino acid sequence for cellular tumor antigen p53.
A nucleotide substitution at position 524 of the coding sequence of the TP53 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 175 in the cellular tumor antigen p53 protein where arginine has been replaced by histidine.
A nucleotide substitution at position 638 of the coding sequence of the TP53 gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 213 in the cellular tumor antigen p53 protein where arginine has been replaced by leucine.
A nucleotide substitution at position 659 of the coding sequence of the TP53 gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 220 in the cellular tumor antigen p53 protein where tyrosine has been replaced by cysteine.
A nucleotide substitution at position 713 of the coding sequence of the TP53 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 238 in the cellular tumor antigen p53 protein where cysteine has been replaced by tyrosine.
A carcinoma that arises from the genitourinary system and has metastasized to other anatomic sites.
Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.
A nucleotide substitution at position 733 of the coding sequence of the TP53 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 245 in the cellular tumor antigen p53 protein where glycine has been replaced by serine.
A condition resulting from the presence of an extra copy of chromosome 22 in chimpanzees. The condition is in many respects similar to Trisomy 21 in humans.
A change in the amino acid residue at position 245 in the cellular tumor antigen p53 protein where glycine has been replaced by aspartic acid.
A nucleotide substitution at position 743 of the coding sequence of the TP53 gene where guanine has been mutated to adenine.
A complex substitution where the nucleotide sequence at positions 743 and 744 of the coding sequence of the TP53 gene has changed from guanine-guanine to adenine-adenine.
A change in the amino acid residue at position 248 in the cellular tumor antigen p53 protein where arginine has been replaced by glutamine.
A nucleotide substitution at position 742 of the coding sequence of the TP53 gene where cytosine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 741 and 742 of the coding sequence of the TP53 gene has changed from cytosine-cytosine to thymine-thymine.
A change in the amino acid residue at position 248 in the cellular tumor antigen p53 protein where arginine has been replaced by tryptophan.
A nucleotide substitution at position 797 of the coding sequence of the TP53 gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 266 in the cellular tumor antigen p53 protein where glycine has been replaced by valine.
A nucleotide substitution at position 797 of the coding sequence of the TP53 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 266 in the cellular tumor antigen p53 protein where glycine has been replaced by glutamic acid.
A nucleotide substitution at position 814 of the coding sequence of the TP53 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 272 in the cellular tumor antigen p53 protein where valine has been replaced by methionine.
A nucleotide substitution at position 818 of the coding sequence of the TP53 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 273 in the cellular tumor antigen p53 protein where arginine has been replaced by histidine.
A nucleotide substitution at position 817 of the coding sequence of the TP53 gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 273 in the cellular tumor antigen p53 protein where arginine has been replaced by cysteine.
A nucleotide substitution at position 818 of the coding sequence of the TP53 gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 273 in the cellular tumor antigen p53 protein where arginine has been replaced by leucine.
A nucleotide substitution at position 844 of the coding sequence of the TP53 gene where cytosine has been mutated to thymine.
A complex substitution where the nucleotide sequence at positions 843 and 844 of the coding sequence of the TP53 gene has changed from cytosine-cytosine to thymine-thymine.
A nucleotide substitution at position 844 of the coding sequence of the TP53 gene where cytosine has been mutated to guanine.
A change in the amino acid residue at position 282 in the cellular tumor antigen p53 protein where arginine has been replaced by glycine.
A variation in the amino acid sequence for a protein encoded by the CDKN2A gene.
A nucleotide substitution at position 89 of the coding sequence of the CDKN2A gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 30 in the cyclin-dependent kinase inhibitor 2 protein where alanine has been replaced by valine.
A nucleotide substitution at position 152 of the coding sequence of the CDKN2A gene where thymine has been mutated to adenine.
A change in the amino acid residue at position 51 in the cyclin-dependent kinase inhibitor 2 protein where valine has been replaced by aspartic acid.
A nucleotide substitution at position 151 of the coding sequence of the CDKN2A gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 51 in the cyclin-dependent kinase inhibitor 2 protein where valine has been replaced by isoleucine.
A nucleotide substitution at position 247 of the coding sequence of the CDKN2A gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 83 in the cyclin-dependent kinase inhibitor 2 protein where histidine has been replaced by tyrosine.
A nucleotide substitution at position 248 of the coding sequence of the CDKN2A gene where adenine has been mutated to cytosine.
A complex substitution where the nucleotide sequence at positions 248 and 249 of the coding sequence of the CDKN2A gene has changed from adenine-cytosine to cytosine-thymine.
A change in the amino acid residue at position 83 in the cyclin-dependent kinase inhibitor 2 protein where histidine has been replaced by proline.
A change in the amino acid residue at position 108 in the cyclin-dependent kinase inhibitor 2 protein where aspartic acid has been replaced by histidine.
A nucleotide substitution at position 322 of the coding sequence of the CDKN2A gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 108 in the cyclin-dependent kinase inhibitor 2 protein where aspartic acid has been replaced by tyrosine.
A nucleotide substitution at position 389 of the coding sequence of the CDKN2A gene where thymine has been mutated to adenine.
A change in the amino acid residue at position 130 in the cyclin-dependent kinase inhibitor 2 protein where leucine has been replaced by glutamine.
A nucleotide substitution at position 439 of the coding sequence of the CDKN2A gene where guanine has been mutated to adenine.
A nucleotide substitution at position 442 of the coding sequence of the CDKN2A gene where guanine has been mutated to adenine.
A variation in the amino acid sequence for a protein encoded by the GNAS gene.
A nucleotide substitution at position 374 of the coding sequence of the GNAS gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 125 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where glutamine has been replaced by arginine.
A nucleotide substitution at position 478 of the coding sequence of the GNAS gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 160 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where arginine has been replaced by cysteine.
A nucleotide substitution at position 602 of the coding sequence of the GNAS gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 201 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where arginine has been replaced by histidine.
A nucleotide substitution at position 601 of the coding sequence of the GNAS gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 201 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where arginine has been replaced by cysteine.
A nucleotide substitution at position 601 of the coding sequence of the GNAS gene where cytosine has been mutated to adenine.
A change in the amino acid residue at position 201 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where arginine has been replaced by serine.
A nucleotide substitution at position 680 of the coding sequence of the GNAS gene where adenine has been mutated to guanine.
A change in the amino acid residue at position 227 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where glutamine has been replaced by arginine.
A nucleotide substitution at position 680 of the coding sequence of the GNAS gene where adenine has been mutated to thymine.
A change in the amino acid residue at position 227 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where glutamine has been replaced by leucine.
A change in the amino acid residue at position 227 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where glutamine has been replaced by proline.
A nucleotide substitution at position 679 of the coding sequence of the GNAS gene where cytosine has been mutated to guanine.
A change in the amino acid residue at position 227 in the guanine nucleotide-binding protein G(s) subunit alpha isoforms short protein where glutamine has been replaced by glutamic acid.
A variation in the amino acid sequence for E3 ubiquitin-protein ligase RNF43.
A nucleotide substitution at position 380 of the coding sequence of the RNF453 gene where guanine has been mutated to cytosine.
A nucleotide substitution at position 420 of the coding sequence of the RNF453 gene where cytosine has been mutated to guanine.
A change in the amino acid residue at position 140 in the E3 ubiquitin-protein ligase RNF43 protein where aspartic acid has been replaced by glutamic acid.
A nucleotide substitution at position 461 of the coding sequence of the RNF453 gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 154 in the E3 ubiquitin-protein ligase RNF43 protein where proline has been replaced by leucine.
A nucleotide substitution at position 505 of the coding sequence of the RNF453 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 169 in the E3 ubiquitin-protein ligase RNF43 protein where alanine has been replaced by threonine.
A nucleotide substitution at position 954 of the coding sequence of the RNF453 gene where guanine has been mutated to thymine.
A change in the amino acid residue at position 318 in the E3 ubiquitin-protein ligase RNF43 protein where glutamic acid has been replaced by aspartic acid.
A change in the nucleotide sequence of exon 9 of the PIK3CA gene.
A change in the nucleotide sequence of exon 20 of the PIK3CA gene.
An epithelioid hemangioendothelioma that arises from the mediastinum.
A central nervous system non-Hodgkin lymphoma which does not respond to treatment.
The reemergence of central nervous system non-Hodgkin lymphoma after a period of remission.
A description of the type of medical device that is found in a subject and is present in its intended location within the body.
An extraskeletal osteosarcoma that arises from the heart. It produces osteoid and bone, and occasionally shows chondroblastic differentiation.
A low-grade sarcoma that arises from the heart. It is composed of spindle or rounded cells in a myxoid stroma. The most common location is the left atrium.
A germ cell tumor that arises within the myocardium or cardiac chambers. The reported cases have been teratomas and yolk sac tumors.
A yolk sac tumor that arises within the myocardium or cardiac chambers.
A nucleotide substitution at position 2389 of the coding sequence of the EGFR gene where thymine has been mutated to adenine.
A nucleotide substitution at position 2390 of the coding sequence of the EGFR gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 797 in the epidermal growth factor receptor protein where cysteine has been replaced by serine.
A change in the amino acid residue at position 797 in the epidermal growth factor receptor protein where cysteine has been replaced by alanine.
A nucleotide substitution at position 2374 of the coding sequence of the EGFR gene where cytosine has been mutated to thymine.
A change in the amino acid residue at position 792 in the epidermal growth factor receptor protein where leucine has been replaced by phenylalanine.
A nucleotide substitution at position 2375 of the coding sequence of the EGFR gene where thymine has been mutated to adenine.
A change in the amino acid residue at position 792 in the epidermal growth factor receptor protein where leucine has been replaced by histidine.
A change in the amino acid residue at position 792 in the epidermal growth factor receptor protein where leucine has been replaced by tyrosine.
A change in the amino acid residue at position 718 in the epidermal growth factor receptor protein where leucine has been replaced by valine.
A nucleotide substitution at position 2153 of the coding sequence of the EGFR gene where thymine has been mutated to adenine.
A change in the amino acid residue at position 718 in the epidermal growth factor receptor protein where leucine has been replaced by glutamine.
A nucleotide substitution at position 2386 of the coding sequence of the EGFR gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 796 in the epidermal growth factor receptor protein where glycine has been replaced by serine.
A nucleotide substitution at position 2386 of the coding sequence of the EGFR gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 796 in the epidermal growth factor receptor protein where glycine has been replaced by arginine.
: A bispecific T-cell engager (BiTE) antibody composed of two single-chain variable fragments (scFv), one directed against the tumor-associated antigen (TAA) CD33 fused to one that is directed against the CD3 antigen found on T-lymphocytes, with potential immunostimulating and antineoplastic activities. Upon administration of anti-CD33/CD3 BiTE antibody AMG 673, this bispecific antibody binds to both the CD3 antigen on cytotoxic T-lymphocytes (CTLs) and the CD33 antigen found on CD33-expressing tumor cells. This activates and redirects CTLs to CD33-expressing tumor cells, which results in the CTL-mediated cell death of CD33-expressing tumor cells. CD33, a myeloid differentiation antigen, is expressed on normal non-pluripotent hematopoietic stem cells and overexpressed on a variety of cancer cell types, including acute myeloid leukemia (AML). It plays a key role in tumor initiation, proliferation and progression.
A bispecific T-cell engager (BiTE) antibody composed of two single-chain variable fragments (scFv), one directed against the tumor-associated antigen (TAA) delta-like protein 3 (DLL3) fused to one that is directed against the CD3 antigen found on T-lymphocytes, with potential immunostimulating and antineoplastic activities. Upon administration of anti-DLL3/CD3 BiTE antibody AMG 757, this bispecific antibody binds to both the CD3 antigen on cytotoxic T-lymphocytes (CTLs) and the DLL3 antigen found on DLL3-expressing tumor cells. This activates and redirects CTLs to DLL3-expressing tumor cells, which results in the CTL-mediated cell death of DLL3-expressing tumor cells. DLL3, a Notch pathway protein, is overexpressed on a variety of cancer cell types. It plays a key role in embryonic development and in tumor initiation and proliferation.
A bispecific T-cell engager (BiTE) antibody composed of two single-chain variable fragments (scFv), one directed against the tumor-associated antigen (TAA) human B-cell maturation antigen (BCMA; TNFRSF17), fused to one that is directed against the CD3 antigen found on T-lymphocytes, with potential immunostimulating and antineoplastic activities. Upon administration of anti-BCMA/CD3 BiTE antibody AMG 701, this bispecific antibody binds to both CD3 on cytotoxic T-lymphocytes (CTLs) and BCMA found on BCMA-expressing tumor cells. This activates and redirects CTLs to BCMA-expressing tumor cells, which results in the CTL-mediated cell death of BCMA-expressing tumor cells. BCMA, a member of the tumor necrosis factor receptor superfamily that is specifically overexpressed on malignant plasma cells, plays a key role in promoting plasma cell survival.
: An antibody-drug conjugate (ADC) composed of a monoclonal antibody against an undisclosed tumor-associated antigen (TAA) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of SC-007 targets and binds to the TAA expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the TAA-expressing cancer cells, through an as of yet unknown mechanism of action.
: An orally available selective estrogen receptor degrader/downregulator (SERD), with potential antineoplastic activity. Upon oral administration, SERD GDC-9545 specifically targets and binds to the estrogen receptor (ER) and induces a conformational change that promotes ER degradation. This prevents ER-mediated signaling and inhibits both the growth and survival of ER-expressing cancer cells.
Chemotherapy-induced nausea and vomiting that does not respond to treatment.
A change in the nucleotide sequence of the PIK3AP1 gene.
A semi-quantitative microscopic finding indicating that 1 percent or more of the nucleated cells in a peripheral leukocyte sample are immature mononuclear cells.
A semi-quantitative microscopic finding indicating that between 6 and 19 percent of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A change in the nucleotide sequence of the ARAF gene.
A change in the nucleotide sequence of the MAP2K1 gene.
A molecular genetic abnormality indicating the presence of multiple copies of the FGF3 gene.
A well differentiated neuroendocrine neoplasm that has spread from the original site of growth to another anatomic site.
An adenoma arising from the mammary gland of a dog.
A molecular genetic abnormality indicating the presence of a sensitizing mutation in the ALK gene.
A molecular abnormality referring to the loss of at least one copy of the MET gene.
Lymphovascular invasion is not present (absent) or is not identified. (AJCC 8th ed.)
Lymphovascular invasion is present or identified. (AJCC 8th ed.)
Presence of lymphovascular invasion unknown or indeterminate. (AJCC 8th ed.)
Lymphatic and small vessel invasion only. (AJCC 8th ed.)
Venous (large vessel) invasion only. (AJCC 8th ed.)
Both lymphatic and small vessel and venous (large vessel) invasion. (AJCC 8th ed.)
A rare sarcoma that arises from the pericardium. The two most common types are angiosarcoma and synovial sarcoma. Patients present with symptoms related to pericardial effusion.
A rare angiosarcoma that arises from the pericardium. Patients present with symptoms related to pericardial effusion.
A rare synovial sarcoma that arises from the pericardium. Patients present with symptoms related to pericardial effusion.
A teratoma that arises within the pericardium.
A malignant germ cell tumor that arises within the pericardium.
A yolk sac tumor that arises within the pericardium.
A non-metastasizing germ cell tumor that arises within the pericardium.
Glioma that does not respond to treatment.
Ependymoma that does not respond to treatment.
The reemergence of SHH-activated medulloblastoma after a period of remission.
SHH-activated medulloblastoma that does not respond to treatment.
Medulloblastoma that is increasing in scope or severity.
Ependymoma that is increasing in scope or severity.
A central nervous system neoplasm that is increasing in scope or severity.
Graft versus host disease that does not respond to steroid treatment.
SHH-activated medulloblastoma that is increasing in scope or severity.
A change in the amino acid residue at position 1010 in the hepatocyte growth factor receptor protein where aspartic acid has been replaced by asparagine.
A recombinant fusion protein consisting of a variant form of the human cytokine interleukin 2 (IL-2; IL2), IL-2 mutein, fused to a human Fc molecule, with potential cell-protective and anti-inflammatory activities. Upon intravenous administration of recombinant human IL-2 mutein/Fc fusion protein AMG 592, the IL-2 mutein moiety binds to its receptors, and activates IL-2-mediated signaling pathways. IL-2 mutein preferentially expands and activates regulatory T-cells (Tregs), thereby preventing inadequate immune responses and restoring immune homeostasis. This may help control or prevent inflammatory reactions as seen in inflammatory-based diseases, such as autoimmune diseases and graft-versus-host disease (GvHD). IL-2 mutein is less able to stimulate natural killer (NK) cells and conventional T-cells, which may lead to reduced toxicity compared to treatment with recombinant IL-2. Fusion to the Fc increases the stability and half-life of AMG 592. Tregs play a key role in the prevention of inflammatory diseases and immune homeostasis.
A change in the nucleotide sequence of MET gene that alters splicing at codon 1010.
An orally available, irreversible, epidermal growth factor receptor (EGFR) mutant-selective inhibitor, with potential antineoplastic activity. Upon oral administration, avitinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the drug-resistant T790M EGFR mutant, which prevents signaling mediated by mutant forms of EGFR. This may both induce cell death and inhibit tumor growth in EGFR-mutated tumor cells. EGFR, a receptor tyrosine kinase that is mutated in a variety of cancers, plays a key role in tumor cell proliferation and tumor vascularization. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced when compared to non-selective EGFR inhibitors, which also inhibit wild-type EGFR.
A change in the amino acid residue at position 792 in the epidermal growth factor receptor protein where leucine has been replaced by another amino acid.
A change in the amino acid residue at position 796 in the epidermal growth factor receptor protein where glycine has been replaced by another amino acid.
A change in the amino acid residue at position 718 in the epidermal growth factor receptor protein where leucine has been replaced by another amino acid.
The ratio of the left ventricular outflow tract (LVOT) velocity to the maximum velocity of the aortic valve.
The minimal cross-sectional area of the flow jet downstream of a cardiac valve.
The ratio of the effective orifice area (EOA) to the body surface area (BSA).
The arithmetic average of the quantitative measurement of the pressure gradient across a predetermined point.
The quantitative measurement of the largest pressure gradient across a predetermined point.
The ratio of the valve area to the body surface area.
The quantitative measurement of the surface area of a valve.
The determination of the amount of weakly bound testosterone present in a sample.
The standard deviation of the subject's bone mineral density score in comparison to the expected normal bone mineral density of a healthy 30-year old adult.
The actual distance between the subject and the eye chart during an eye assessment.
The planned distance between the subject and the eye chart during an eye assessment.
A decrease in the number of corpora lutea within the ovary.
An increase in the number of corpora lutea within the ovary.
An increase in the amount of surface erosion.
The presence of red blood cells within hepatocytes of the liver parenchyma.
An increase in the amount of osteoclasts.
A severity result of one, on a five level scale.
A severity result of two, on a three level scale.
A severity result of two, on a four level scale.
A severity result of two, on a five level scale.
A severity result of three, on a three level scale.
A severity result of three, on a four level scale.
A severity result of three, on a five level scale.
A severity result of four, on a four level scale.
A severity result of four, on a five level scale.
A severity result of five, on a five level scale.
Adenocarcinoma arising from the lung of a sheep.
Myeloid recovery after bone marrow transplantation. It manifests with the production of new blood cells. It takes approximately two to four weeks after the bone marrow is infused with the transplanted stem cells for the recovery to occur.
A bispecific humanized monoclonal antibody against human CD3, a T-cell surface antigen, and human G-protein coupled receptor family C group 5 member D (GPRC5D), a tumor-associated antigen (TAA), with potential antineoplastic activity. Upon administration, anti-CD3/anti-GPRC5D bispecific monoclonal antibody JNJ-64407564 binds to both CD3 on T-cells and GPRC5D expressed on certain tumor cells. This results in the cross-linking of T-cells and tumor cells, and induces a potent cytotoxic T-lymphocyte (CTL) response against GPRC5D-expressing tumor cells. GPRC5D is overexpressed on certain tumors, such as multiple myeloma, while minimally expressed on normal, healthy cells, and plays a key role in tumor cell proliferation.
A finding indicating that a cancer continues to grow despite the intervention with platinum therapy.
Recurrent ovarian carcinoma that is resistant to platinum therapy.
A proprietary, biodegradable, poly (lactic-co-glycolic acid) (PLGA) nanoparticle-based formulation composed of synthetic vaccine particles (SVP) encapsulating the macrolide antibiotic rapamycin (SVP-R), with immunosuppressant and drug-protective activities. Upon administration of SVP-R, the SVP moiety is selectively and preferentially taken up through endocytosis by antigen-presenting cells (APCs), located in the spleen and lymph nodes, specifically dendritic cells (DCs). Rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, prevents DC maturation, induces tolerogenic DCs, induces regulatory T-cells (Tregs), blocks activation of effector T-cells, induces B-cell tolerance, reduces B-cell activation, and prevents antibody formation, thereby inducing immune tolerance. When co-administered with a biological immunogenic drug known to induce the production of anti-drug antibodies (ADA), SVP-R is able to prevent ADA formation, which prevents the unwanted neutralizing effects of ADAs, increases efficacy of the biological drug, and permits sustained therapeutic activity and repeated administration of the biological drug. In the presence of a specific target antigen, SVP-R is able to prevent an antigen-specific immune response and induces antigen-specific immune tolerance. Compared to the administration of free rapamycin, SVP-R induces long-lasting immunological tolerance.
A humanized, bispecific monoclonal antibody (BsAb) against human CD3, a T-cell surface antigen, and the human cell surface glycoprotein CD38, a tumor-associated antigen (TAA), with potential antineoplastic activity. Upon administration, anti-CD38/anti-CD3 bispecific monoclonal antibody GBR 1342 binds to both CD3 on T-cells and CD38 expressed on certain tumor cells. This results in the cross-linking of T-cells and tumor cells, and induces a potent cytotoxic T-lymphocyte (CTL) response against CD38-expressing tumor cells. CD38, a type II transmembrane glycoprotein, is present on various immune cells and hematologic malignancies; its expression has been correlated with poor prognosis. GBR 1342 uses the proprietary bispecific engagement by antibodies based on the T-cell receptor (BEAT) platform.
A change in the amino acid residue at position 59 in the GTPase KRas protein where alanine has been replaced by another amino acid.
A change in the amino acid residue at position 117 in the GTPase KRas protein where lysine has been replaced by another amino acid.
A proprietary antibody-drug conjugate (ADC) composed of XMT-1535, a proprietary, humanized monoclonal antibody against human sodium-dependent phosphate transport protein 2B (SLC34A2; NaPi2b), site-specifically linked, via a protease cleavable linker, to the proprietary cytotoxic aurastatin derivative auristatin F-HPA (AF-HPA; auristatin F-hydroxypropylamide), with potential antineoplastic activity. XMT-1536 is produced via the proprietary dolaflexin ADC conjugation platform, which promotes the conjugation of between 10 and 15 AF-HPA payload molecules to each XMT-1535 antibody. Upon administration of XMT-1536, the antibody moiety targets and binds to NaPi2b expressed on tumor cells. Upon binding, internalization by endosomes/lysosomes, and enzymatic cleavage, the AF-HPA binds to tubulin and inhibits microtubule polymerization, which results in G2/M phase arrest and apoptosis of NaPi2b-expressing tumor cells. NaPi2b, a tumor-associated antigen (TAA), is overexpressed on a variety of cancer cells and plays a key role in the transport of inorganic phosphate (Pi) and the maintenance of phosphate homeostasis.
A proprietary humanized monoclonal antibody against human sodium-dependent phosphate transport protein 2B (SLC34A2; NaPi2b), with potential antineoplastic activity. Upon administration of XMT-1535, the antibody targets and binds to NaPi2b expressed on tumor cells. Although the tumor cell killing effects of XMT-1535 are not established, this binding may induce an antibody-dependent cellular cytotoxicity (ADCC)-mediated immune response against NaPi2b-expressing tumor cells, and/or may inhibit NaPi2b-mediated sodium and phosphate ion cotransport activity and ion-dependent tumor cell signaling. NaPi2b, a tumor-associated antigen (TAA), is overexpressed on a variety of tumor cells. It plays a key role in the transport of inorganic phosphate (Pi) and the maintenance of phosphate homeostasis.
The reemergence of a lymphoproliferative disorder after a period of remission.
The reemergence of EBV-related lymphoma after a period of remission.
A change in the nucleotide sequence of the ABCD1 gene.
Any agent that can alter hormone levels or modulate hormone effects.
A finding indicating that chronic lymphocytic leukemia does not respond to treatment with Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib.
Non-squamous non-small cell lung carcinoma that has spread extensively to other anatomical sites or is no longer responding to treatment.
A B-cell non-Hodgkin lymphoma that arises from the brain, meninges, or spinal cord.
Breast carcinoma that does not respond to treatment.
Colorectal carcinoma that does not respond to treatment.
Melanoma that does not respond to treatment.
Gastric carcinoma that does not respond to treatment.
An ovarian carcinoma associated with mutation of a gene in the BRCA family.
The reemergence of BRCA-mutated ovarian carcinoma after a period of remission.
The reemergence of a childhood malignant solid neoplasm after a period of remission.
A childhood malignant solid neoplasm that does not respond to treatment.
A mutation in PIK3CD, the gene encoding the p110delta catalytic subunit of PI3K, that results in induction of PI3K signaling. Mutations of this type are associated with immunodeficiency 14 (PASLI: activated PI3k-delta syndrome, p110-delta-activating mutation causing senescent T-cells, lymphadenopathy, and immunodeficiency).
A malignant solid neoplasm that occurs during childhood.
A malignant solid neoplasm that is not amenable to surgical resection.
The reemergence of a WHO grade II glioma after a period of remission.
The reemergence of a WHO grade III glioma after a period of remission.
An orally bioavailable antagonist of the adenosine A2A receptor (A2AR; ADORA2A), with potential immunomodulating and antineoplastic activities. Upon administration, A2AR antagonist AZD4635 selectively binds to and inhibits A2AR expressed on T-lymphocytes. This blocks tumor-released adenosine from interacting with A2AR and prevents the adenosine/A2AR-mediated inhibition of T-lymphocytes. This results in the proliferation and activation of T-lymphocytes, and stimulates a T-cell-mediated immune response against tumor cells. A2AR, a G protein-coupled receptor, is highly expressed on the cell surfaces of T-cells and, upon activation by adenosine, inhibits T-cell proliferation and activation. Adenosine is often overproduced by cancer cells and plays a key role in immunosuppression.
An antibody against the inhibitory T-cell receptor T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3; TIM3; hepatitis A virus cellular receptor 2; HAVCR2), with potential immune checkpoint inhibitory and antineoplastic activities. Following administration, anti-TIM-3 antibody BMS-986258 binds to TIM-3 that is expressed on certain T-cells, including tumor infiltrating lymphocytes (TILs). This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes and enhances cytotoxic T-cell-mediated tumor cell lysis, which together result in decreased tumor growth. TIM-3, a transmembrane protein and immune checkpoint receptor, is associated with tumor-mediated immune suppression.
A mature B-cell neoplasm or B lymphoblastic leukemia/lymphoma that has spread to other anatomical sites or is no longer responding to treatment.
A quantitative microscopic finding indicating that less than 20,000 of the total number of nucleated cells in a peripheral leukocyte sample are immature mononuclear cells.
A craniopharyngioma that is not amenable to surgical resection.
The reemergence of a craniopharyngioma after a period of remission.
A human, non-agonistic immunoglobulin G1 (IgG1) monoclonal antibody directed against the cell surface glycoprotein ADP-ribosyl cyclase 1 (CD38) with potential immunomodulating and antineoplastic activities. Anti-CD38 monoclonal antibody TAK-079 specifically binds to CD38 that is expressed on human plasmablasts, plasma cells, NK cells and activated T- and B-cells. This may trigger antibody-dependent cellular cytotoxicity (ADCC), cell lysis and depletion of CD38-expressing cells. Additionally, TAK-079 does not induce CD38-dependent signaling and does not promote cytokine activation in peripheral blood mononuclear cells (PMBCs). CD38, a type II transmembrane glycoprotein, is overexpressed on cells associated with autoimmune diseases and hematologic malignancies.
A molecular abnormality indicating rearrangement of the EGFR gene.
Malignant thymoma that does not respond to treatment.
A genetic rearrangement that refers to any inversion involving the ROS1 gene.
A change in the sequence of one or more genes that are involved in the hedgehog signaling pathway.
A tablet composed of the non-opioid derivative of morphine dextromethorphan (DM) and the aminoketone bupropion, with potential analgesic, antidepressant and anti-agitation activities. Upon oral administration, the DM component may act as a weak N-methyl-D-aspartate (NMDA) receptor antagonist, a sigma-1 receptor agonist and an inhibitor of the serotonin and norepinephrine transporters, which together may alleviate pain, agitation, anxiety and depression. While the bupropion component acts as a norepinephrine and dopamine reuptake inhibitor and a central nicotinic acetylcholine receptor antagonist, which is beneficial in the treatment of depression. Additionally, bupropion may increase the bioavailability of DM, thus prolonging the therapeutic effects of DM.
An antibody-drug conjugate (ADC) composed of an antibody targeting the cell surface antigen CD48 that is conjugated to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), via a proprietary next-generation PEGylated glucuronide linker, with potential antineoplastic activity. Following intravenous administration, the antibody moiety of anti-CD48 ADC SGN-CD48A binds to CD48 on the surface of tumor cells. Following internalization of the ADC, the MMAE binds to tubulin and inhibits microtubule polymerization, which may result in G2/M phase cell cycle arrest and apoptosis in CD48-expressing tumor cells. CD48, a member of the signaling lymphocyte activation molecule (SLAM) family of immune cell receptors, is involved in T-cell activation and leukocyte trafficking. Additionally, CD48 is expressed on the surface of multiple myeloma cells at significantly higher levels than it is expressed on normal lymphocytes and monocytes. The linkage system in SGN-CD48A improves stability, reduces off-target uptake, and enables conjugation of larger numbers of MMAE/antibody than other systems, resulting in increased specificity against CD48-positive cells.
A change in the nucleotide sequence of the DDR2 gene.
A change in the nucleotide sequence of a GNAI family gene.
A change in the nucleotide sequence of the ERBB2 gene that either inhibits expression of the receptor tyrosine-protein kinase erbB-2 protein or results in the translation of an inactive receptor tyrosine-protein kinase erbB-2 protein.
A change in the nucleotide sequence of the KIT gene that originated in non-germline cells.
A T-cell immunostimulatory factor, derived from the soluble form of the lymphocyte-activation gene 3 (LAG-3) protein, with potential antineoplastic activity. Upon administration, alone or in combination with tumor antigens, IMP321 binds with high affinity to MHC class II molecules expressed by dendritic cells (DC), potentially resulting in DC maturation, DC migration to lymph nodes, enhanced DC cross-presentation of antigens to T cells, and antitumor cytotoxic T cell responses.
A flavone and cyclin dependent kinase (CDK) inhibitor with potential antineoplastic activity. Riviciclib selectively binds to and inhibits Cdk4/cyclin D1, Cdk1/cyclin B and Cdk9/cyclin T1, serine/threonine kinases that play key roles in the regulation of the cell cycle and cellular proliferation. Inhibition of these kinases leads to cell cycle arrest during the G1/S transition, thereby leading to an induction of apoptosis, and inhibition of tumor cell proliferation.
A small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity. Adavosertib selectively targets and inhibits WEE1, a tyrosine kinase that phosphorylates cyclin-dependent kinase 1 (CDK1, CDC2) to inactivate the CDC2/cyclin B complex. Inhibition of WEE1 activity prevents the phosphorylation of CDC2 and impairs the G2 DNA damage checkpoint. This may lead to apoptosis upon treatment with DNA damaging chemotherapeutic agents. Unlike normal cells, most p53 deficient or mutated human cancers lack the G1 checkpoint as p53 is the key regulator of the G1 checkpoint and these cells rely on the G2 checkpoint for DNA repair to damaged cells. Annulment of the G2 checkpoint may therefore make p53 deficient tumor cells more vulnerable to antineoplastic agents and enhance their cytotoxic effect.
The investigation involved the analysis of relevant production records in view of supporting the identification of possible causes for the adverse event.
The device affects the ability of the blood to clot which may be induced by chemical, mechanical, or thermal properties of the device.
A synthetic oligonucleotide based on a proprietary double stem-loop immunomodulator design with potential immunostimulating activity. Lefitolimod binds to and activates intracellular Toll-like receptor 9 (TLR9) in monocytes/macrophages, plasmacytoidal and myeloid dendritic cells (DCs), and natural killer (NK) cells, initiating immune signaling pathways and inducing T-helper 1 cell (Th1) production leading to the production of memory T cells and a Th1-mediated immune response. By activating the immune system, MGN1703 may attack tumor associated antigen (TAAs). TLR9 is a member of the TLR family, which plays a fundamental role in pathogen recognition and activation of innate immunity.
An Fc-domain optimized, humanized monoclonal antibody directed against cancer stem cells (CSCs), with potential immunomodulating and antineoplastic activities. After binding of enoblituzumab to an as of yet not elucidated target expressed on CSCs and differentiated tumor cells, this agent may induce an antibody-dependent cell-mediated cytotoxicity (ADCC) against CSCs. CSCs are tumor initiating cells that are able to self-renew and are responsible for tumor cell growth and resistance.
An orally available, highly water-soluble lysine prodrug of the synthetic small molecule BAL27862 with potential antitumor activity. Upon administration of lisavanbulin and conversion into the active form BAL27862, this agent binds to tubulin at a site distinct from the vinca-alkaloid-binding site, and prevents tubulin polymerization and destabilizes microtubules, ultimately leading to cell cycle arrest, blockage of cell division and an induction of cell death in cancer cells.
The hydrochloride salt form of avadomide, an orally available pleiotropic pathway modulator with potential antineoplastic activity.
An orally bioavailable inhibitor of the class I phosphoinositide 3-kinase (PI3K) alpha isoform with potential antineoplastic activity. Serabelisib selectively inhibits PI3K alpha kinase, including mutations of PIK3CA, in the PI3K/Akt/mTOR pathway, which may result in tumor cell apoptosis and growth inhibition in PI3K alpha-expressing tumor cells. By specifically targeting class I PI3K alpha, this agent may be more efficacious and less toxic than pan PI3K inhibitors. Dysregulation of the PI3K/Akt/mTOR pathway is frequently found in solid tumors and results in promoting tumor cell growth, survival, and resistance to chemotherapy and radiotherapy; PIK3CA, one of the most highly mutated oncogenes, encodes the p110-alpha catalytic subunit of the class I PI3K.
An antibody drug conjugate (ADC) consisting of a humanized IgG1 monoclonal antibody targeting the MUC16 protein (CA-125) conjugated to, via a cleavable linker, the antimicrotubulin agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. The monoclonal antibody moiety of sofituzumab vedotin selectively binds to MUC16. After internalization of the drug conjugate and proteolytic cleavage of the linker, MMAE binds to tubulin and inhibits its polymerization, which results in G2/M-phase growth arrest and tumor cell apoptosis. MUC16, a transmembrane protein, is overexpressed on the cell surface of more than 80 percent of ovarian cancer cells but not on healthy cells.
Stage IA includes: T1a, N0, M0. T1a: Tumor confined to the vagina, measuring 2.0 cm or less. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Stage I includes: T1, N0, M0. T1: Uterine corpus adenosarcoma with tumor limited to the uterus. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th Ed.)
Penile cancer with extranodal extension of lymph node metastases or pelvic lymph node metastases. (from AJCC 8th Ed.)
A finding about one or more characteristics of prostate cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to adenocarcinomas and squamous cell carcinomas of the prostate gland. It does not apply to sarcomas, urothelial cell carcinomas, and urothelial carcinoma of bladder involving prostate. (from AJCC 8th Ed.)
Prostate cancer in which the tumor involves both sides. (from AJCC 8th Ed.)
Stage IVB includes: Any T, N0, M1, PSA: Any, Grade Group: Any. N0: Prostate cancer with no positive regional nodes. M1: Prostate cancer with distant metastasis. (AJCC 8th ed.)
Kidney cancer in which the tumor measures 7 cm or less in greatest dimension and is limited to the kidney. (from AJCC 8th Ed.)
A finding about one or more characteristics of renal pelvis and ureter cancer, following the rules of the TNM AJCC v8 classification system. This classification system applies to renal pelvis and ureter urothelial (transitional cell) carcinoma, including histologic variants micropapillary and nested subtypes. It does not apply to renal cell carcinomas (are staged according to the classification for kidney), renal medullary carcinomas (are staged according to the classification for kidney), collecting duct carcinomas (are staged according to the classification for kidney), lymphomas (are staged according to the classification for Hodgkin and non-Hodgkin lymphoma), and mesenchymal tumors (are staged according to the classification for soft tissue sarcoma of the abdomen and thoracic visceral organs). (from AJCC 8th Ed.)
Bladder cancer with tumor invading perivesical soft tissue, macroscopically (extravesical mass). (from AJCC 8th Ed.)
Stage IIIA includes: (T3a, T3b, T4a, N0, M0); (T1-T4a, N1, M0). T1: Tumor invades lamina propria (subepithelial connective tissue). T2: Tumor invades muscularis propria. T3: Tumor invades perivesical soft tissue. T3a: Tumor invades perivesical soft tissue, microscopically. T3b: Tumor invades perivesical soft tissue, macroscopically (extravesical mass). T4a: Extravesical tumor invades directly into prostatic stroma, uterus, vagina. N0: No regional lymph node metastasis. N1: Single regional lymph node metastasis in the true pelvis (perivesical, obturator, internal and external iliac, or sacral lymph node). M0: No distant metastasis. (AJCC 8th ed.)
Urethral cancer with multiple regional lymph node metastasis in the inguinal region or true pelvis [perivesical, obturator, internal (hypogastric) and external iliac], or presacral lymph node. (from AJCC 8th Ed.)
An anatomic stage for nodular lymphocyte predominant Hodgkin lymphoma based on the Ann Arbor classification criteria.
An anatomic stage for mantle cell lymphoma based on the Ann Arbor classification criteria.
A recombinant fusion protein consisting of human cytokine interleukin 22 (IL-22) fused to a human immunoglobulin G2 (IgG2)-Fc, with potential cell protective activity. Upon intravenous administration of recombinant human IL-22 IgG2-Fc, IL-22 binds to its cognate receptor IL-22R, which is highly expressed in parenchymal tissues and epithelial cells at mucosal surfaces. This leads to the activation of IL-22/IL-22R-mediated signal transduction pathways, and results in the activation of signal transducer and activator of transcription 3 (STAT3). STAT3 activation may have a protective and regenerative effect and may protect against the development of various inflammatory and immunological diseases. Specifically, recombinant human IL-22 IgG2-Fc may protect intestinal stem cells from dying due to acute graft-versus-host disease (aGvHD). IL-22, produced by various immune cells and upregulated during inflammation, plays a key role in controlling immune responses and bacterial infection, and in the enhancement of intestinal barrier function, gut immunity, and tissue repair.
A subjective score of 10 on a pain scale that ranges from 0: No Pain to 10: Worst Possible Pain.
An indication that expression of CD3 has not been detected in a sample.
A semi-quantitative microscopic finding indicating that more than 5 percent of the nucleated cells in a bone marrow sample are immature mononuclear cells.
A change in the nucleotide sequence of the FGFR3 gene that that results in constitutive activation of fibroblast growth factor 3 and its downstream signaling pathways.
A proprietary humanized monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-PD-1 monoclonal antibody MGA012 binds to and inhibits PD-1 and its downstream signaling pathways. This may restore immune function through the activation of T-cells and cell-mediated immune responses against tumor cells. PD-1, a transmembrane protein in the immunoglobulin superfamily (IgSF) expressed on T-cells, functions as an immune checkpoint that negatively regulates T-cell activation and effector function when activated by its ligands programmed cell death ligand 1 (PD-L1) or 2 (PD-L2); it plays an important role in tumor evasion from host immunity.
A change which occurs at a particular time, affecting all age groups and cohorts uniformly.
A molecular genetic abnormality indicating the presence of multiple copies of the ROS1 gene.
A therapeutic cancer vaccine composed of a replication-defective, serotype 5 adenovirus (Ad5) with the viral genes early 1 (E1), early 2b (E2b), and early 3 (E3) deleted, and the human transcription factor brachyury encoded, with potential immunostimulating and antineoplastic activities. Upon subcutaneous administration, the adenoviral brachyury vaccine ETBX-051 expresses the brachyury protein. The expressed brachyury may induce a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells expressing brachyury, thereby resulting in both immune-mediated inhibition of tumor cell proliferation and tumor cell death. Deletion of the E1, E2b and E3 genes from Ad5 prevents anti-adenovirus immune responses. Brachyury, a tumor-associated antigen (TAA) and member of the T-box family of transcription factors, is overexpressed in a variety of tumor types. It plays an important role in cancer progression and metastasis.
An orally bioavailable, selective inhibitor of human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon oral administration, FGFR4 antagonist INCB062079 specifically and irreversibly binds to the cysteine residue at position 552 (Cys 552) that is within the active site of FGFR4. This blocks FGFR4 autophosphorylation and activation of receptor tyrosine kinase activity that would normally occur after binding to its ligand fibroblast growth factor 19 (FGF19), which both inhibits FGFR4-mediated signaling and leads to an inhibition of tumor cell proliferation in FGF19- and FGFR4-overexpressing cells. FGFR4, a receptor tyrosine kinase, is involved in angiogenesis and in the proliferation, differentiation, and survival of tumor cells. FGFR4 expression is associated with poor prognosis. FGF19 is overexpressed by certain tumor cell types.
A semi-quantitative microscopic finding indicating that less than 30 percent of the nucleated cells in a peripheral leukocyte sample are immature mononuclear cells.
No change in bowel function or oral intake
Mild hallucinations (e.g., perceptual distortions)
Corrected serum calcium of >ULN-11.5 mg/dL; >ULN-2.9 mmol/L; Ionized calcium >ULN-1.5 mmol/L
Decrease in sexual interest not adversely affecting relationship
Combined area of ulcers <1 cm; nonblanchable erythema of intact skin with associated warmth or edema
Evidence of autoimmune reaction involving a non-essential organ or function (e.g., hypothyroidism)
Moderate localized facial edema; limiting instrumental ADL
Symptomatic separation of the nail bed from the nail plate or nail loss; limiting instrumental ADL
Significant deformity, hypoplasia, or asymmetry, unable to be remediated by prosthesis or covered by clothing; limiting self care ADL
Symptomatic, urgent intervention indicated; ablation
Blood bilirubin >5 mg/dL; coagulation modifier indicated (e.g., defibrotide); reversal of flow on ultrasound
Life-threatening consequences; urgent intervention, intubation, or ventilatory support indicated
An antibody-drug conjugate (ADC) composed of a monoclonal antibody against the tumor-associated antigen (TAA) the proto-oncogene c-Met (hepatocyte growth factor receptor; HGFR) linked to an as of yet undisclosed cytotoxic agent, with potential antineoplastic activity. Upon intravenous administration, the monoclonal antibody moiety of HTI-1066 targets and binds to c-Met expressed on tumor cells. Upon binding and internalization, the cytotoxic agent is released and kills the c-Met-expressing cancer cells, through an as of yet unknown mechanism of action. c-Met, a receptor tyrosine kinase overexpressed or mutated in many tumor cell types, plays key roles in tumor cell proliferation, survival, invasion, metastasis and tumor angiogenesis.
A change in the nucleotide sequence of the WT1 gene.
A proprietary enhanced stabilization chemistry (ESC)-stabilized conjugate composed of the liver-targeted ligand N-acetylgalactosamine (GalNAc) conjugated to small-interfering RNAs (siRNAs) directed against the liver-expressed enzyme aminolevulinic acid synthase 1 (delta-aminolevulinate synthase 1; ALAS1; ALAS-1) that can potentially be used in the treatment of acute hepatic porphyrias (AHPs). Upon subcutaneous administration of givosiran, the GalNAc moiety targets and binds with high affinity to asialoglycoprotein receptors (ASGPRs) expressed on hepatocytes. Once inside the cell, the siRNAs bind to and silence ALAS1 mRNA and inhibit both the translation and expression of the ALAS1 protein. This prevents delta-aminolevulinic acid (ALA) formation, decreases 5-ALA levels and prevents the production of porphyrins and hemes, such as porphobilinogen (PBG). AHPs are a group of metabolic disorders caused by deficiencies of specific enzymes that are responsible for hemoglobulin biosynthesis within the liver, which leads to the accumulation of toxic intermediates, such as ALA and PBG. ALAS1, a liver-expressed, rate-limiting enzyme in the heme biosynthesis pathway, is responsible for the formation of ALA from succinyl-CoA and glycine. ESC enables the subcutaneous dosing of givosiran with increased efficacy, durability and a wide therapeutic index as compared to non-ESC GalNAc-siRNA conjugates.
Tumor with distant metastasis. (WHO Classification of Tumors of the Lung, Pleura, Thymus and Heart, 2015)
A nucleotide substitution at position 1801 of the coding sequence of the BRAF gene where adenine has been mutated to guanine.
A nucleotide substitution at position 734 of the coding sequence of the TP53 gene where guanine has been mutated to adenine.
A change in the amino acid residue at position 282 in the cellular tumor antigen p53 protein where arginine has been replaced by tryptophan.
A nucleotide substitution at position 322 of the coding sequence of the CDKN2A gene where guanine has been mutated to cytosine.
A change in the amino acid residue at position 127 in the E3 ubiquitin-protein ligase RNF43 protein where arginine has been replaced by proline.
An antibody-drug conjugate (ADC) composed of a monoclonal antibody against human mucin 16 (MUC16; cancer antigen 125; CA125; FLJ14303) conjugated to monomethyl auristatin E (MMAE), an auristatin derivative and potent microtubule disrupting agent, with potential antineoplastic activity. Upon administration, anti-MUC16/MMAE ADC DMUC4064A binds to MUC16 located on the tumor cell surface. After internalization of the agent, the MMAE moiety is released and binds to tubulin and inhibits its polymerization, which results in G2/M phase arrest and apoptosis. MUC16, a member of the mucin family glycoproteins, is overexpressed in a variety of tumor cells and plays a key role in tumor cell proliferation.
A blood concentration of prostate specific antigen greater than 4 ng/mL.
A change in the nucleotide sequence of MET gene that alters splicing at codon 963.
A severity result of one, on a four level scale.
A synthetic macrocyclic peptide inhibitor of the terminal complement protein C5, with potential anti-inflammatory and cell protective activities. Upon subcutaneous administration, complement C5 inhibitor RA101495 binds to a unique site in terminal complement protein C5, which blocks C5 cleavage into C5a and C5b and prevents the C5b-dependent assembly of the membrane-attack complex (MAC). RA101495 also inhibits the interaction between C5b and C6, thereby further blocking MAC assembly. This prevents MAC-mediated lysis and destruction of red blood cells (RBCs) that occurs in complement-mediated diseases, such as paroxysmal nocturnal hemoglobinuria (PNH), generalized myasthenia gravis (gMG) and lupus nephritis (LN). C5, a complement pathway protein, is expressed at high levels by the liver.
An oropharyngeal squamous cell carcinoma which is negative for p16INK4a by immunohistochemistry. This negative immunohistochemistry result does not exclude human papillomavirus infection.
An antibody-drug conjugate (ADC) comprised of an aglycosylated human anti-CD74 IgG1 antibody (SP7219) that has been genetically modified to incorporate the non-natural amino acid (nnAA) para-azidomethyl-L-phenylalanine (pAMF), which is site-specifically conjugated to a non-cleavable dibenzocyclooctyne (DBCO)-maytansinoid linker-warhead, with potential antineoplastic activity. The antibody moiety of anti-CD74 ADC STRO-001 targets and binds to the CD74 expressed on tumor cells; upon internalization, the maytansinoid linker-warhead moiety binds to tubulin and disrupts microtubule assembly/disassembly dynamics, which results in the inhibition of both cell division and cell growth of CD74-expressing tumor cells. CD74, a transmembrane glycoprotein and tumor-associated antigen (TAA) involved in major histocompatibility complex (MHC) class II protein formation and localization, is a receptor for macrophage migration inhibitory factor (MIF; MMIF). MIF binding induces intramembrane cleavage of CD74, which liberates the cytosolic intracellular domain (ICD) of CD74 and regulates the expression of genes involved in promoting cell survival. CD74 is overexpressed on cells from hematologic B-lineage malignancies.
A carbohydrate-based immunostimulant comprised of the Globo H hexasaccharide 1 (Globo H) epitope linked to the immunostimulant carrier protein keyhole limpet hemocyanin (KLH), with potential antineoplastic activity. Upon administration of adagloxad simolenin, the carbohydrate antigen Globo H may stimulate a cytotoxic T-lymphocyte (CTL) response against Globo H-expressing tumor cells, thereby decreasing tumor cell proliferation. Globo H is a tumor associated antigen (TAA) commonly found on a variety of tumor cells including breast cancer cells. KLH improves antigenic immune recognition and T-cell responses.
A finding about one or more characteristics of mycosis fungoides and Sezary syndrome, following the rules of the TNM AJCC v8 classification system as they pertain to distant metastases (visceral). (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of lacrimal gland carcinoma, following the rules of the TNM AJCC v8 classification system.
Advanced stage adult lymphoma based on the Lugano classification criteria. It includes stages III and IV. (from AJCC 8th Ed.)
A very rare, benign or malignant lung tumor with myoepithelial differentiation.
A finding about one or more characteristics of uterine corpus carcinoma or carcinosarcoma, following the rules of the TNM AJCC v8 classification system. This classification system does not apply to uterine corpus sarcomas: leiomyosarcomas, endometrial stromal sarcomas, and adenosarcomas. These sarcomas are staged according to the classification for uterine corpus sarcomas. (from AJCC 8th Ed.)
A finding about one or more characteristics of a gestational trophoblastic neoplasm, following the rules of the TNM AJCC v8 classification system. This classification applies to the following placental neoplasms: invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumor, and epithelioid trophoblastic tumor. Complete and partial hydatidiform tumors are not included in this classification. (from AJCC 8th Ed.)
Stage IIC includes: (Any pT/TX, N3, M0, S0); (Any pT/TX, N3, M0, S1). TX: Testicular cancer in which the primary tumor cannot be assessed. N3: Testicular cancer with metastasis with a lymph node mass larger than 5 cm in greatest dimension. M0: Testicular cancer without evidence of distant metastasis. S0: Marker study levels within normal limits. S1: LDH less than 1.5 x N and hCG (mlU/mL) less than 5,000 and AFP (ng/mL) less than 1,000. N indicates the upper limit of normal for the LDH assay. (AJCC 8th ed.)
Eyelid carcinoma with tumor measuring more than 20 mm but 30 mm or less in greatest dimension involving the full thickness of the eyelid. (from AJCC 8th Ed.)
A pathologic finding about one or more characteristics of conjunctival melanoma, following the rules of the TNM AJCC v8 classification system as they pertain to staging of the primary tumor.
Iris melanoma with tumor confluent with or extending into the ciliary body, without secondary glaucoma. (from AJCC 8th Ed.)
Stage IIIA includes: (T2c-d, N0, M0); (T3b-c, N0, M0); (T4a, N0, M0). T2c: Tumor size category 2 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in largest diameter. T2d: Tumor size category 2 with ciliary body involvement and extraocular extension less than or equal to 5 mm in largest diameter. T3b: Tumor size category 3 with ciliary body involvement. T3c: Tumor size category 3 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in largest diameter. T4a: Tumor size category 4 without ciliary body involvement and extraocular extension. N0: No regional lymph node metastasis. M0: No distant metastasis. (AJCC 8th ed.)
Tumor invasion of choroid, pars plana, ciliary body, lens, zonules, iris, or anterior chamber. (from AJCC 8th Ed.)
Erythropoietic protoporphyria (EPP) is characterized by cutaneous photosensitivity (usually beginning in infancy or childhood) that results in tingling, burning, pain, and itching within 30 minutes after exposure to sun or ultraviolet light and may be accompanied by swelling and redness. Symptoms (which may seem out of proportion to the visible skin lesions) may persist for hours or days after the initial phototoxic reaction. Photosensitivity remains for life. Multiple episodes of acute photosensitivity may lead to chronic changes of sun-exposed skin (lichenification, leathery pseudovesicles, grooving around the lips) and loss of lunulae of the nails. Approximately 20%-30% of individuals with EPP have some degree of liver dysfunction, which is typically mild with slight elevations of the liver enzymes. Up to 5% may develop more advanced liver disease which may be accompanied by motor neuropathy similar to that seen in the acute porphyrias.
Hyperphosphatemic familial tumoral calcinosis (HFTC) is characterized by: Ectopic calcifications (tumoral calcinosis) typically found in periarticular soft tissues exposed to repetitive trauma or prolonged pressure (e.g., hips, elbows, and shoulders); and Painful swellings (referred to as hyperostosis) in the areas overlying the diaphyses of the tibiae (and less often the ulna, metacarpal bones, and radius). The dental phenotype unique to HFTC includes enamel hypoplasia, short and bulbous roots, obliteration of pulp chambers and canals, and pulp stones. Less common are large and small vessel calcifications that are often asymptomatic incidental findings on radiologic studies but can also cause peripheral vascular insufficiency (e.g., pain, cold extremities, and decreased peripheral pulses). Less frequently reported findings include testicular microlithiasis and angioid streaks of the retina.
Shwachman-Diamond syndrome (SDS) is characterized by: exocrine pancreatic dysfunction with malabsorption, malnutrition, and growth failure; hematologic abnormalities with single- or multilineage cytopenias and susceptibility to myelodysplasia syndrome (MDS) and acute myelogeneous leukemia (AML); and bone abnormalities. In almost all affected children, persistent or intermittent neutropenia is a common presenting finding, often before the diagnosis of SDS is made. Short stature and recurrent infections are common.
NDHMSR is an autosomal recessive neurodevelopmental disorder characterized by severely delayed psychomotor development, severe intellectual disability, and involuntary movements, including stereotypic movements, spasticity, and dystonia. Affected individuals are are usually unable to walk independently and have poor or absent speech. Some patients have intractable seizures (summary by Lemke et al., 2016).
ALKKUCS is an autosomal recessive severe neurodevelopmental disorder characterized by arthrogryposis, brain abnormalities associated with cerebral parenchymal underdevelopment, and global developmental delay. Most affected individuals die in utero or soon after birth. Additional abnormalities may include hypotonia, dysmorphic facial features, and involvement of other organ systems, such as cardiac or renal. The few patients who survive have variable intellectual disability and may have seizures (summary by Gueneau et al., 2018).
Immunodeficiency-55 is an autosomal recessive primary immunodeficiency characterized by intrauterine growth retardation, natural killer (NK) cell deficiency, and chronic neutropenia. Most patients also have postnatal growth retardation. Other clinical manifestations include mild facial dysmorphism, dry or eczematous skin, and recurrent infections with both viruses and bacteria. The disorder appears to result from a defect in DNA replication causing blockade of immune cell differentiation in the bone marrow, particularly affecting NK cells (summary by Cottineau et al., 2017).
IECEE2 is a neurodevelopmental disorder characterized in most patients by onset of seizures in infancy or childhood and associated with global developmental delay and variable intellectual disability. The seizure type and severity varies, and seizures may be intractable in some patients. Some patients are severely affected, unable to walk or speak, whereas others show some development. Additional neurologic features, including cortical blindness, dystonia, and spasticity, may occur. Mutations occur de novo (summary by Hamdan et al., 2017). For a discussion of genetic heterogeneity of IECEE, see IECEE1 (617711).
EIEE58 is a severe neurodevelopmental disorder characterized by onset of refractory seizures in the first days or months of life. Affected individuals have global developmental delay with intellectual disability, usually with absent speech and inability to walk. Additional features include optic atrophy with poor or absent visual fixation, hypotonia, and spasticity (summary by Hamdan et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
DEDSM is a neurodevelopmental disorder characterized by global developmental delay, variable intellectual disability, and early-onset seizures with a myoclonic component. Most patients have delayed motor development and show abnormal movements, including ataxia, dystonia, and tremor (summary by Hamdan et al., 2017).
NEDMEBA is an autosomal recessive neurodegenerative disorder characterized by global developmental delay, severe intellectual disability with poor or absent speech and autistic stereotypic behaviors, microcephaly, early-onset generalized seizures, and hypotonia (summary by Marin-Valencia et al., 2018).
NEDSGA is an autosomal dominant disorder characterized by global developmental delay apparent from infancy or early childhood, resulting in variable intellectual disability that can range from profound with absent speech to mild with an ability to attend special schools. Most affected individuals show irritability, stiffness, and hypertonia early in life, which progresses to spasticity and impaired gait later. Some patients may develop seizures of variable severity early in life (summary by Martin et al., 2017).
NEDMAGA is a neurodevelopmental disorder characterized by infantile-onset global developmental delay with severe to profound intellectual disability, mildly delayed walking with broad-based and unsteady gait, and absence of meaningful language. Patients have features of autism, with repetitive behaviors and poor communication, but usually are socially reactive and have a happy demeanor. More variable neurologic features include mild seizures, spasticity, and peripheral neuropathy (summary by Palmer et al., 2017).
COXPD34 is an autosomal recessive disorder resulting from a defect in mitochondrial function. The phenotype is variable, but may include congenital sensorineural deafness, increased serum lactate, and hepatic and renal dysfunction. Neurologic function is relatively preserved (summary by Menezes et al., 2015). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
COXPD35 is an autosomal recessive disorder characterized mainly by global developmental delay with intellectual disability, microcephaly, and early-onset myoclonic and other types of seizures. Affected individuals have variable deficiencies of mitochondrial respiratory enzyme complexes resulting from a defect in mitochondrial metabolism (summary by Kernohan et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
PCLD3 is an autosomal dominant disorder characterized by the development of multiple liver cysts that usually becomes apparent in adulthood. Liver cysts range in size and number, and the clinical severity is variable. Most patients also have a few renal cysts, but they do not result in significant renal disease or renal failure (summary by Besse et al., 2017). For a discussion of genetic heterogeneity of polycystic liver disease, see PCLD1 (174050).
PCLD4 is an autosomal dominant disease characterized by adult-onset of liver cysts arising from the bile duct epithelium. Some patients may develop a few kidney cysts, but these are often incidental and do not result in renal failure (summary by Cnossen et al., 2014). For a discussion of genetic heterogeneity of polycystic liver disease, see PCLD1 (174050).
Patients with SSFSC have short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. Congenital heart defects are variably observed and appear to involve primarily the cardiac outflow tract (Tan et al., 2017).
Leber congenital amaurosis with early-onset deafness is an autosomal dominant syndrome manifesting as early-onset and severe photoreceptor and cochlear cell loss. Some patients show extinguished responses on electroretinography and moderate to severe hearing loss at birth (Luscan et al., 2017).
CMTDIG is an autosomal dominant neurologic disorder with a highly variable phenotype. Most affected individuals have onset in the first or second decades of slowly progressive distal motor weakness and atrophy, resulting in gait instability and distal upper limb impairment, as well as distal sensory impairment. More severely affected individuals may have pes cavus and claw hands and become wheelchair-bound, whereas other affected individuals have later onset with a milder disease course. Electrophysiologic studies tend to show median motor nerve conduction velocities (NCV) in the 'intermediate' range, between 25 and 45 m/s (summary by Berciano et al., 2017). In a review of intermediate CMT, Berciano et al. (2017) noted that advanced axonal degeneration may induce secondary demyelinating changes resulting in decreased NCV and attenuated compound muscle action potential (CMAP) in median nerve conduction studies. They thus suggested that testing the upper arm, axilla to elbow, may provide more accurate assessment of NCV and CMAP and reveal an intermediate phenotype (review by Berciano et al., 2017). For a discussion of genetic heterogeneity of CMTDI, see 606482.
Patients with biallelic mutations in the ADCY3 gene show hyperphagia within the first 2 years of life and develop severe obesity. Other features include hyposmia or anosmia, and some patients exhibit mild to moderate intellectual disability (Saeed et al., 2018).
Multiple synostoses syndrome-4 is characterized by fusion of carpal and tarsal bones, as well as conductive hearing loss (Terhal et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of multiple synostoses syndrome, see SYNS1 (186500).
Hypomyelinating leukodystrophy-14 is an autosomal recessive neurodevelopmental disorder characterized by hypotonia, almost complete lack of motor or cognitive skills, and absent language development. Additional features include spasticity and intractable seizures; many patients also have perceptive hearing loss and/or blindness. Most patients require tube feeding or ventilatory support, and most die in the first years of life. Brain imaging shows hypomyelination, small caudate and putamen, and cerebral and cerebellar atrophy (summary by Hamilton et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080.
NDPLHS is an autosomal dominant disorder characterized by developmental stagnation or regression apparent in the first years of life and manifest as loss of purposeful hand movements, loss of language, and intellectual disability. Additional features may include stereotypic movements, dystonia, gait abnormalities, sleep disturbances, and small hands and feet. The phenotype is reminiscent of Rett syndrome (RTT; 312750) (summary by Yoo et al., 2017).
Erythrocytosis-5 is an autosomal dominant clinical condition characterized by increased red cell mass and typically elevated hemoglobin concentration and hematocrit. Some patients have increased serum EPO levels (summary by Zmajkovic et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of familial erythrocytosis, see ECYT1 (133100).
Juvenile myoclonic epilepsy-10 is an autosomal dominant seizure disorder with variable manifestations, even within families. Affected individuals have febrile, myoclonic, tonic-clonic, or absence seizures, although several seizure types can occur in the same individual. The age of onset also shows great variability: some patients present in the first years of life, whereas other have onset of seizures in teenage years. EEG typically shows 3.5 to 5 Hz polyspike wave discharges. There is evidence of incomplete penetrance (summary by Bailey et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of juvenile myoclonic epilepsy, see 254770.
Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330).
Orofaciodigital syndrome-18 is characterized by short stature, brachymesophalangy, pre- and postaxial polysyndactyly, and stocky femoral necks, as well as oral anomalies and dysmorphic facial features (Thevenon et al., 2016).
Keratoconus-9, a degenerative corneal disease with onset during adolescence, is characterized by corneal ectasia, thinning, and cone-shaped protrusion that results in reduced vision (Hao et al., 2017). For a discussion of genetic heterogeneity of keratoconus, see 148300.
FFEVF4 is an autosomal dominant seizure disorder characterized by onset of focal seizures in the first years of life. Some patients may have secondary generalization and/or mild developmental deficits (summary by Vanoye et al., 2014). For a discussion of genetic heterogeneity of FFEVF, see FFEVF1 (604364).
Hypomyelinating leukodystrophy-15 is an autosomal recessive neurodegenerative disorder characterized by onset of motor and cognitive impairment in the first or second decade of life. Features include dystonia, ataxia, spasticity, and dysphagia. Most patients develop severe optic atrophy, and some have hearing loss. Brain imaging shows hypomyelinating leukodystrophy with thin corpus callosum. The severity of the disorder is variable (summary by Mendes et al., 2018) For a discussion of genetic heterogeneity of HLD, see 312080.
Osteogenesis imperfecta type XVIII (OI18) is characterized by congenital bowing of the long bones, wormian bones, blue sclerae, vertebral collapse, and multiple fractures in the first years of life (Doyard et al., 2018).
Multiple mitochondrial dysfunctions syndrome-6 is an autosomal recessive severe neurodegenerative disorder with onset in early childhood. Affected individuals may have initial normal development, but show neurologic regression in the first year of life. They have hypotonia, inability to walk, poor speech, intellectual disability, and motor abnormalities, such as ataxia, dystonia, and spasticity. Some patients may die in childhood. Laboratory evidence indicates that the disorder results from mitochondrial dysfunction (summary by Vogtle et al., 2018). For a general description and a discussion of genetic heterogeneity of multiple mitochondrial dysfunctions syndrome, see MMDS1 (605711).
Among the 5 taste modalities recognized by humans (bitter, sweet, sour, umami, and salty), bitter taste plays an important protective role because many plant toxins have a bitter taste. The G protein-coupled receptor encoded by TAS2R16 mediates response to salicin, amygdalin, and many bitter beta-glucopyranosides. Beta-glucopyranosides are synthesized by over 2,500 plant and insect species as a protection against predators. This family also includes various toxic cyanogenic glycosides (summary by Soranzo et al., 2005).
Spermatogenic failure-24 is characterized by multiple morphologic abnormalities of the flagella (MMAF), including absent, short, coiled, bent, and irregular-caliber flagella. Malformations of the sperm head have also been observed. In addition, patients exhibit very low sperm concentrations and total sperm counts per ejaculate (Dong et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Spermatogenic failure-25 is characterized by small testes and infertility, with severe oligozoospermia or azoospermia due to maturation arrest at the primary spermatocyte stage (Okutman et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Spermatogenic failure-26 is characterized by acephalic spermatozoa, due to breakage that occurs in the midpiece of the sperm (Sha et al., 2018). For a general phenotypic description and discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Hypomyelinating leukodystrophy-16 is an autosomal dominant neurologic disorder characterized by onset of hypotonia, nystagmus, and mildly delayed motor development in infancy. Affected individuals have motor disabilities, including ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties. Brain imaging typically shows hypomyelination, leukodystrophy, and thin corpus callosum (summary by Simons et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080.
Spermatogenic failure-27 (SPGF27) is characterized by infertility due to multiple morphologic abnormalities of the sperm flagella (MMAF), a phenotype also designated as 'dysplasia of the fibrous sheath,' 'short tails,' or 'stump tails.' Spermatozoa in the ejaculate exhibit short, irregular, coiled, or absent flagella. Ultrastructural analysis shows loss of the central pair of microtubules, loss of the inner dynein arms, and peripheral doublet disorganization (Lores et al., 2018). For a discussion of the phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
LDLCQ7 is a quantitative trait affecting LDL levels that is effected through the NPC1L1 gene, which is responsible for the intestinal absorption of cholesterol. NPC1L1 is the molecular target for the drug ezetimibe, and variants in this gene affect response to this drug.
The RH-null phenotype designates rare individuals whose red blood cells lack all Rh antigens. Two RH-null types, the regulator type (268150) and the amorph type, arising from independent genetic mechanisms have been distinguished. The regulator type is caused by mutation in the RHAG gene (180297). The amorph type arises from mutations at the RH locus itself that silence Rh expression. The RH locus contains the RHD (111680) and RHCE genes tandemly arranged at chromosome 1p36-p34. Four genes must therefore be silenced to produce the RH-null phenotype. The absence of the D antigen, produced by the RHD gene, is common in the human population; the D-negative phenotype may result from deletion or genetic alteration of the RHD gene. The RH-null amorph phenotype thus arises from inactivating mutations in RHCE on a D-negative background (summary by Huang et al., 1998, Huang et al., 2000). Clinically, Rh-null patients present mild to moderate hemolytic anemia; cells exhibit characteristic morphologic and functional abnormalities including spherocytosis, stomatocytosis, and diminished lifespan. Rh-null patients rarely develop antibodies without stimulation, and most cases occur in response to pregnancy or transfusion (Silvy et al., 2015).
Methemoglobinemia is a clinical condition in which more than 1% of hemoglobin is oxidized to methemoglobin, a type of hemoglobin that contains the ferric (Fe3+) form of iron. Patients with hemolobin M are cyanotic but otherwise asymptomatic. If the mutation occurs in the hemoglobin alpha subunit (141800), cyanosis is apparent at birth, whereas if the beta chain is affected, cyanosis appears later or intensifies when beta subunit production increases. If a newborn carries a fetal M hemoglobin (gamma subunit; 142250), cyanosis disappears when the complete gamma-beta-switch occurs (summary by Mansouri and Lurie, 1993).
Methemoglobinemia is a clinical condition in which more than 1% of hemoglobin is oxidized to methemoglobin, a type of hemoglobin that contains the ferric (Fe3+) form of iron. Patients with hemoglobin M are cyanotic but otherwise asymptomatic. If the mutation occurs in the hemoglobin alpha subunit, cyanosis is apparent at birth, whereas if the beta chain (141900) is affected, cyanosis appears later or intensifies when beta subunit production increases. If a newborn carries a fetal M hemoglobin (gamma subunit; 142250), cyanosis disappears when the complete gamma-beta-switch occurs (summary by Mansouri and Lurie, 1993).
Spondyloepimetaphyseal dysplasia of the Di Rocco type (SEMDDR) is characterized by short stature, joint pain, and genu varum, as well as SEMD involving primarily the hips but also affecting the wrists, hands, knees, and ankles. Patients also exhibit variable degrees of metaphyseal and spine involvement (Di Rocco et al., 2018).
Familial erythrocytosis-6 is characterized by an increased oxygen affinity of hemoglobin (Hb), which results in decreased delivery of oxygen into the peripheral tissues and compensatory polycythemia. Patients are generally asymptomatic, as compensatory polycythemia assures normal oxygen tissue delivery. Patients have normal red cell morphology (summary by Kralovics and Prchal, 2000). Wajcman and Galacteros (2005) noted that although high oxygen affinity hemoglobins are usually well tolerated in young patients, they can lead to thrombotic complications in older patients or when they are associated with another cause that increases thrombotic risk. Wajcman and Galacteros (2005) also noted that the effect of increased oxygen affinity of Hb caused by an alpha chain variant (see 617981) is usually milder than that caused by a beta chain variant.
Familial erythrocytosis-7 is characterized by an increased oxygen affinity of hemoglobin (Hb), which results in decreased delivery of oxygen into the peripheral tissues and compensatory polycythemia. Patients are generally asymptomatic, as compensatory polycythemia assures normal oxygen tissue delivery. Patients have normal red cell morphology (summary by Kralovics and Prchal, 2000). Wajcman and Galacteros (2005) noted that although high oxygen affinity hemoglobins are usually well tolerated in young patients, they can lead to thrombotic complications in older patients or when they are associated with another cause that increases thrombotic risk. Wajcman and Galacteros (2005) also noted that the effect of increased oxygen affinity of Hb caused by an alpha chain variant is usually milder than that caused by a beta chain variant (see 617980).
Ververi-Brady syndrome is characterized by mild developmental delay, mildly impaired intellectual development and speech delay, and mild dysmorphic facial features. Affected individuals can usually attend mainstream schools with support, and may also show autistic features (summary by Ververi et al., 2018).
JABELS is an autosomal recessive neurodevelopmental disorder characterized by developmental delay and intellectual disability with additional variable features. Patients have onset of symptoms in infancy, but the severity is highly variable. Some patients have social interaction and learn to walk but have an ataxic gait and abnormal movements, such as tremor or dystonia, whereas others do not achieve any motor control and are unable to speak. Additional features may include retinal anomalies, visual impairment, microcephaly, abnormal foot or hand posturing, and kyphoscoliosis; some patients have dysmorphic facial features or seizures. Brain imaging typically shows cerebellar atrophy and hypoplasia of the corpus callosum (summary by et al., 2016 and Bertoli-Avella et al., 2018).
DIDOD is a disorder characterized by global developmental delay apparent from infancy, intellectual disability or learning difficulties, behavioral abnormalities, dysmorphic features, and obesity. The severity of the phenotype and additional features are variable (summary by Jansen et al., 2018).
Hyperphosphatemic familial tumoral calcinosis is a rare autosomal recessive metabolic disorder characterized by the progressive deposition of basic calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone (Chefetz et al., 2005). The biochemical hallmark of tumoral calcinosis is hyperphosphatemia caused by increased renal absorption of phosphate due to loss-of-function mutations in the FGF23 or GALNT3 (601756) gene. The term 'hyperostosis-hyperphosphatemia syndrome' is sometimes used when the disorder is characterized by involvement of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis. Although some have distinguished HHS from FTC by the presence of bone involvement and the absence of skin involvement (Frishberg et al., 2005), Ichikawa et al. (2010) concluded that the 2 entities represent a continuous spectrum of the same disease, best described as familial hyperphosphatemic tumoral calcinosis. HFTC is considered to be the clinical converse of autosomal dominant hypophosphatemic rickets (ADHR; 193100), an allelic disorder caused by gain-of-function mutations in the FGF23 gene and associated with hypophosphatemia and decreased renal phosphate absorption (Chefetz et al., 2005; Ichikawa et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of HFTC, see 211900.
Hyperphosphatemic familial tumoral calcinosis is a rare autosomal recessive metabolic disorder characterized by the progressive deposition of basic calcium phosphate crystals in periarticular spaces, soft tissues, and sometimes bone (Chefetz et al., 2005). The biochemical hallmark of tumoral calcinosis is hyperphosphatemia caused by increased renal absorption of phosphate due to loss-of-function mutations in the FGF23 (605380) or GALNT3 (601756) gene. The term 'hyperostosis-hyperphosphatemia syndrome' is sometimes used when the disorder is characterized by involvement of the long bones associated with the radiographic findings of periosteal reaction and cortical hyperostosis. Although some have distinguished HHS from FTC by the presence of bone involvement and the absence of skin involvement (Frishberg et al., 2005), Ichikawa et al. (2010) concluded that the 2 entities represent a continuous spectrum of the same disease, best described as familial hyperphosphatemic tumoral calcinosis. HFTC is considered to be the clinical converse of autosomal dominant hypophosphatemic rickets (ADHR; 193100), an allelic disorder caused by gain-of-function mutations in the FGF23 gene and associated with hypophosphatemia and decreased renal phosphate absorption (Chefetz et al., 2005; Ichikawa et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of HFTC, see 211900.
Ehlers-Danlos syndrome classic-like-2 is characterized by severe joint and skin laxity, osteoporosis involving the hips and spine, osteoarthritis, soft redundant skin that can be acrogeria-like, delayed wound healing with abnormal atrophic scarring, and shoulder, hip, knee, and ankle dislocations. Variable features include gastrointestinal and genitourinary manifestations, such as bowel rupture, gut dysmotility, cryptorchidism, and hernias; vascular complications, such as mitral valve prolapse and aortic root dilation; and skeletal anomalies (Blackburn et al., 2018). See 606408 for another classic-like EDS syndrome. For a discussion of the classification of EDS, see 130000.
Autosomal recessive deafness-57 is characterized by symmetric bilateral moderate to severe hearing loss, represented by gently downward-sloping audiograms. The hearing loss may be mildly progressive (Guan et al., 2018).
Early infantile epileptic encephalopathy-64 is a neurodevelopmental disorder characterized by onset of seizures usually in the first year of life and associated with intellectual disability, poor motor development, and poor or absent speech. Additional features include hypotonia, abnormal movements, and nonspecific dysmorphic features. The severity is variable: some patients are unable to speak, walk, or interact with others as late as the teenage years, whereas others may have some comprehension (summary by Straub et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Congenital disorder of glycosylation with defective fucosylation is an autosomal recessive multisystem disorder apparent from birth. Affected infants have poor growth, failure to thrive, hypotonia, skeletal anomalies, and delayed psychomotor development with intellectual disability. Additional highly variable congenital defects may be observed (summary by Ng et al., 2018). Genetic Heterogeneity of Congenital Disorders of Glycosylation with Defective Fucosylation See also CDGF2 (618323), caused by mutation in the FCSK gene (608675) on chromosome 16q22. For an overview of congenital disorders of glycosylation (CDG), see CDG1A (212065) and CDG2A (212066).
Hypomyelinating leukodystrophy-17 is an autosomal recessive neurodevelopmental disorder characterized by poor, if any, development apparent from infancy. Affected individuals never learn to walk or speak, and have early-onset multifocal seizures, spasticity, poor overall growth, and microcephaly (up to -10 SD). Brain imaging shows multiple abnormalities, including cerebral and cerebellar atrophy, thin corpus callosum, abnormal signals in the basal ganglia, and features suggesting hypo- or demyelination. Some patients may die in childhood (summary by Shukla et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080.
Early infantile epileptic encephalopathy-65 is characterized by onset of intractable seizures of various types within 6 months of birth, severe to profound psychomotor developmental delay, and mild facial dysmorphism (summary by Nakashima et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Hyperekplexia-4 is an autosomal recessive severe neurologic disorder apparent at birth. Affected infants have extreme hypertonia and appear stiff and rigid. They have little if any development, poor or absent visual contact, and no spontaneous movement, consistent with an encephalopathy. Some patients have early-onset refractory seizures, and many have inguinal or umbilical hernia. Most patients die in the first months of life due to respiratory failure or other complications (summary by Piard et al., 2018). For a general description and a discussion of genetic heterogeneity of hyperekplexia, see HKPX1 (149400).
IECEE3 is an autosomal dominant neurologic disorder characterized by delayed psychomotor development, early-onset refractory seizures, and intellectual disability. The severity of the phenotype is highly variable: some patients may be nonverbal and nonambulatory with spastic quadriparesis and poor eye contact, whereas others have moderate intellectual disability (summary by Fassio et al., 2018). For a discussion of genetic heterogeneity of IECEE, see IECEE1 (617711).
DFNB109 is characterized by bilateral congenital severe to profound sensorineural hearing loss. In addition, affected individuals exhibit vestibular dysplasia on CT scan, although they do not manifest problems with balance or movement (Rohacek et al., 2017).
Erythropoietic porphyria-2 is an autosomal dominant metabolic disorder of heme biosynthesis, resulting in abnormal accumulation of the heme biosynthesis intermediate protoporphyrin IX (PPIX). Affected individuals may have photosensitivity (summary by Yien et al., 2017) For discussion of genetic heterogeneity of EPP, see EPP1 (177000).
CYP2C8 is involved in the metabolism of a multitude of chemically diverse medications, including nonsteroidal antiinflammatory drugs, thiazolidinediones, and chemotherapeutic agents (summary by Zhou et al., 2017). Backman et al. (2016) reviewed the role of CYP2C8 in clinically relevant drug interactions.
In type IV atherosclerotic lesions a dense accumulation of extracellular lipid occupies an extensive but well-defined region of the intima. This type of extracellular lipid accumulation is known as the lipid core. A fibrous tissue increase is not a feature, and complications such as defects of the lesion surface and thrombosis are not present. The type IV lesion is also known as atheroma. Type IV is the first lesion considered advanced in this classification because of the severe intimal disorganization caused by the lipid core. The characteristic core appears to develop from an increase and the consequent confluence of the small isolated pools of extracellular lipid that characterize type III lesions. The increase in lipid is believed to result from continued insudation from the plasma. The nature and derivations of the lipid that constitutes the core are discussed in the section on the extracellular matrix at the end of this report. Type IV lesions, when they first appear in younger people, are found in the same locations as adaptive intimal thickenings of the eccentric type. Thus, atheroma is, at least initially, an eccentric lesion. [PMID:7648691]
An elevated proportion of T cells that express human leukocyte antigen (HLA)-DR. HLA-DR is an MHC class II cell surface receptor that presents antigens (peptides of at least 9 amino acids), thereby constituting a ligand for the T-cell receptor. HLA-DR can be upregulated in response to immune stimulation. [PMID:11531958]
A lack of coordination of leg movement manifested by undershoot or overshoot of the intended position of the leg. [HPO:mtaboada, PMID:25573808]
A type of incomitant strabismus in which the angle of deviation varies as the patient's gaze shifts upwards and/or downwards. [ORCID:0000-0003-0986-4123]
A reduction in the numbers of pro-B cells (defined by coexpression of CD34 and CD19). Earlier B-cell precursors are defined by expressing surface CD34 and cytoplasmic TdT in the absence of CD19. []
Lamellar cataracts with associated linear lens opacities radially extending towards the periphery of the lens. [ORCID:0000-0003-0986-4123]
Anterior chamber cells with 6-15 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp. [PMID:16196117]
Anterior chamber cells with 1-5 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp. [PMID:16196117]
Anterior chamber cells with less than one cell in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp. [PMID:16196117]
Anterior chamber cells with 16-25 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp. [PMID:16196117]
Anterior chamber cells with 26-50 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp. []
Anterior chamber cells with more than 50 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp. [PMID:16196117]
Increased tendency of choiroidal blood vessels to allow fluids to leak characterized by multifocal choroidal hyperfluorescence on indocyanine green angiography (ICGA). [PMID:25709392]
A type of cataract that shows a spectacular display of multiple colours that glitters with the change of incident light like an illuminated Christmas tree. [PMID:27190856]
Any structural anomaly of the principal vein draining blood from the upper portion of the body and delivering it to the right ventricle of the heart. [MP:0006064]
Any structural anomaly of the principal vein draining blood from the lower portion of the body. [MP:0006063]
Any structural abnormality of the left atrium. []
Any structural abnormality of the right atrium. []
Bleeding occuring within the fovea. [ORCID:0000-0003-0986-4123]
Bleeding between the neurosensory retina and the retinal pigment epithelium (RPE) arising from the choroidal or retinal circulation. [ORCID:0000-0003-0986-4123]
Golden, scintillating, particulate reflection noted on fundus examination (typically in the macula and sparing the fovea). The term tapetal is used to describe this 'metallic' sheen appearance as it is thought to be similar to the 'tapetal' reflex seen in the eyes of certain animals. []
Cyclodeviation is defined as the rotation of an eyeball along the anteroposterior axis and cyclotropia as a misalignment of cyclodeviation between the two eyes. [ORCID:0000-0003-0986-4123, PMID:15731772]
A functional anomaly of the muscles of the eye. []
A functional anomaly of the superior oblique muscle, a fusiform muscle that originates in the upper, medial side of the orbit. The superior oblique muscle abducts, depresses and internally rotates the eye, and is the only extraocular muscle innervated by the fourth cranial nerve. [ORCID:0000-0003-0986-4123]
Decreased strength of the superior oblique muscle. []
Mechanical limitation of the range of movement of the superior oblique muscle. [ORCID:0000-0003-0986-4123]
Reduced ocular movement of the superior oblique muscle which improves on testing ductions, typically associated with neurogenic palsy. [ORCID:0000-0003-0986-4123]
A functional anomaly of the inferior oblique muscle, an extraocular muscle that has its origin on the maxillary bone just posterior to the inferior medial orbital rim and lateral to the nasolacrimal canal and that is innervated by the inferior branch of the oculomotor nerve. [ORCID:0000-0003-0986-4123]
Mechanical limitation of the range of movement of the inferior oblique muscle. [ORCID:0000-0003-0986-4123]
Decreased strength of the inferior oblique muscle. [ORCID:0000-0003-0986-4123]
A functional anomaly of the inferior rectus muscle, which is innervated by the inferior division of oculomotor nerve and functions in the depression, adduction, and lateral rotation (extortion) of the eye. [ORCID:0000-0003-0986-4123]
Decreased strength of the inferior rectus muscle. [ORCID:0000-0003-0986-4123]
A functional anomaly of the superior rectus muscle, an extraocular muscle that is innervated by the superior division of the oculomotor nerve, and whose primary function is the elevation of the globe. [ORCID:0000-0003-0986-4123]
A schwannoma (benign, usually encapsulated slow growing tumor composed of Schwann cells) located in the orbit. []
A functional anomaly of the medial rectus muscle, an extraocular muscle that is innervated by the inferior division of the oculomotor nerve and whose sole action is the adduction of the eyeball. [ORCID:0000-0003-0986-4123]
A type of blepharitis that affects the eyelid skin, base of the eyelashes, and the eyelash follicles. [ORCID:0000-0003-0986-4123]
A type of epicanthus in which more extensive epicanthal folds with their origins in the eyebrow cover, pass in front of and lateral to the medial canthus (middle corner of the eye). [ORCID:0000-0003-0986-4123]
A type of facial cleftlocated near to but not directly on the midline of the face. []
As seen in a typical cleft lip, a cleft of the lip is found in the region of the cupid's bow. The nostril is cleft through the alar dome and extends above onto the nasal dorsum. It passes medial to a normal, but dys- topic, medial canthus. There is an alveolar cleft between the central and lateral incisors that extends above through the pyriform margin lateral to the anterior nasal spine; the nasal septum is not involved. The bony cleft extends through the nasal bone or between the junction of the nasal bone and frontal process of the maxilla. Above the cleft lip, the clefting of the alar dome is associated with deviation to the opposite side of the shortened and broadened columella and nasal tip. Extension of the soft tissue cleft onto the nasal dorsum can be manifest as a series of vertical soft tissue furrows and ridges. Vertical inner canthal dysto- pia and severe telecanthus mark the superior aspect of the Number 1 facial cleft. A cranial soft tissue extension characterized by a tongue-like projection of the frontal hairline delineates the number 13 cleft. Skeletal clefting of the maxilla may extend posteriorly to form a complete cleft of the hard and soft palate. The maxilla is hypoplastic in all three dimensions. There is a keel-shaped alveolus and anterior open bite. Normal septation is preserved between the nasal cavity and the hypoplastic maxillary antrum on the affected side. Distortion of the nasal skeleton produces gross flattening of the nasal dorsum. There is asymmetry of the pterygoid plates, of the greater and lesser wings of the sphenoid, and of the floor of the anterior cranial fossa. The distortion of the cranial base may result in a mild plagiocephaly. [PMID:2503273]
As is typically seen in isolated cleft cases, a cleft of the lip is present. There is hypoplasia, but not true notching of the ala nasi with flattening of the lateral part of the nose. The nasal root is broadened, with lateral displacement of the inner canthus. The palpebral fissure and lacrimal drainage system are not disturbed. The alveolar cleft is through the lateral incisor area and extends to the pyriform aperture. There is normal septation between the nasal cavity and maxillary sinus. Notching at the junction between the nasal bone is present, as is a broad, flat frontal process of the maxilla. Transverse ethmoid enlargement produces orbital hypertelorism. Above the cleft of the lip and palate is a true broad cleft of the nostril that is medial to the intact, but laterally displaced, tail of the alar cartilage. A shallow soft tissue groove extends superiorly to the asymmetrically widened nasal root. The lacrimal system, palpebral fissures, and eyebrows remain intact. The alveolar cleft extends posteriorly as a complete unilateral cleft of the hard and soft palate. The nasal septum is intact but deviated to the opposite side. The nasal cavity remains separated from the normally pneumatized, although hypoplastic, maxilla on the cleft side. Above the nasomaxillary notching, the ethmoid sinus is less well developed, and there is no pneumatization of the frontal sinus on this side. Anterior rotation of the greater and lesser wings of the sphenoid occurs on the cleft side in relation to the narrower orbit and smaller ethmoid sinus. There is mild asymmetry of the anterior cranial fossa, which is narrower on the cleft side. The cranium is brachycephalic with marked occipital flattening. [PMID:2503273]
As in the Number 1 and Number 2 clefts, this cleft extends through the lip in the region of the typical cleft lip; however, it does not extend through the base. The cleft continues superiorly to involve the inner canthus and lower eyelid medial to the inferior lacrimal punctum, thereby disrupting the nasolacrimal system. Microphthalmia may be present. The alveolar cleft is between the lateral incisor and the canine. Absent septation between the nasal cavity and maxillary antrum, together with the distortion of the frontal process of the maxilla and lacrimal fossa, produces direct communication between the orbit, maxillary sinus, and nose. There is hypoplasia of the soft tissue margins of the cleft in the vertical dimension. This produces extreme soft tissue deficiency between the alar base and the cleft of the medial aspect of the lower eyelid. The inferior lacrimal punctum is evident at the lateral margin of the lower eyelid cleft. The lacrimal drainage system ends as an opening directly onto the cheek without communication into the nasal cavity. The globe is normal in size, but it is displaced inferiorly and laterally. The nasal septum shows the characteristic distortion seen in typical cleft lip and palate. There is absence of septation between the nasal cavity on the cleft side and the maxilla. The maxilla is hypoplastic in three dimensions, with a marked reduction in pneumatization. Superior extension of the skeletal clefting into the medial portion of the orbital floor and into the inferior orbital rim in the region of the frontal process of the maxilla allows direct communication between the orbit above and the nasomaxillary region below. There is mild narrowing of the ethmoid sinus and of the body of the sphenoid on the cleft side. The pterygoid process appears anatomically normal, but less displaced from the midline compared with that of the noncleft side. Both the orbit and the floor of the anterior cranial fossa are inferiorly displaced. [PMID:2503273]
The cleft lip is midway between the philtral ridge and the commissure of the mouth. The cleft is lateral to the normally shaped and placed nasal ala and passes onto the cheek. The cleft extends through the lower eyelid lateral to the punctum. The lacrimal system and inner canthus are normal. Microphthalmia may be present. The alveolar cleft passes between the lateral incisor and canine, as in the Number 3 cleft. The cleft passes around the pyriform aperture and continues through the portion of the maxillary sinus medial to the infraorbital foramen. The cleft terminates at the medial end of the inferior orbital rim. There is severe vertical soft tissue deficiency in a Number 4 cleft, with the medial margins of the cleft lip extending directly into the medially placed cleft of the lower eyelid. Within the medial segment of the right-sided cleft lip, muscle elements are apparently absent. Muscle bunching is noted in the ipsilateral lateral lip segment, as is seen in a typical unilateral cleft lip. The anatomically normal nasal ala is superiorly displaced in association with a severe deficiency in the overall nasal length. Marked dystopia of the right globe results in its inferior displacement into the medially deficient orbital floor and inferior rim. Both globes are otherwise normal. The complete palatal cleft passes through the maxilla medial to the infraorbital foramen and extends to the medial portion of the inferior orbital rim without evidence of an intact maxillary sinus. Bony septation persists medially, thereby separating the nasal cavity from the orbit, maxillary sinus, and mouth, which are contiguous. Marked midfacial hypoplasia is present. The cleft is manifest as asymmetry of the body of the sphenoid; it is smaller on the right, with asymmetric placement of the pterygoid plates relative to the midline. The orbital floor cleft has no communication with the inferior orbital fissure. The cleft does not extend to the skull base, but there is marked facial asymmetry associated with plagiocephaly. [PMID:2503273]
The cleft of the lip is just medial to the oral commissure and extends across the cheek as a furrow. It ends as a cleft at the junction of the middle and lateral third of the lower eyelid. Microphthalmia is frequently present. The alveolar cleft is through the premolar region and extends superiorly through the orbit at the inferolateral part of the rim and floor. There is a vertical soft tissue deficiency between the lateral portion of the lip and the lower eyelid cleft. The left side of the nose shows vertical shortening, and the left alar base is displaced superiorly. Facial asymmetry secondary to the skeletal abnormality is reflected by a vertical orbital dystopia. However, bothglobes are normal, and there is no abnormality of the upper eyelids, eyebrow, forehead, or frontal hairline. The skeletal clefts vary, ranging from a narrow skeletal furrow that traverses the anterior maxillary wall as on the rightto a broad cleft of the maxilla lateral to the infraorbital foramen and maxillary sinus. This latter cleft enters the inferolateral orbital rim and floor without posterior communication with the inferior orbital fissure on the left side. Medial collapse of the lateral maxillary segments is present bilaterally, with reduction in the transverse dimensions of the maxillary arch. Manifestations of the skeletal disturbance in the sphenoid include a shortening and thickening of the lateral orbital walls in the region of the greater wing and mild asymmetric placement of the pterygoid plates relative to the midline. The right-sided pterygoid plates are smaller and closer to the midline. There is minimal asymmetry of the cranial base and calvarium. [PMID:2503273]
This is an upper lateral orbital cleft. The soft tissue deformity is in the lateral one-third of the upper eyelid, and the bony cleft is through the superolateral orbital angle. Microphthalmia is present. The superolateral bony deficiency of the orbits allows a lateral displacement of the globes. The lateral one-third of the upper eyelid and the outer canthus are distorted, thus preventing apposition to the globe. The upper eyelid does not have a true cleft. A soft tissue furrow radiates superiorly and posterisphenoid is symmetric and normal. Mild cranial base asymmetry is reflected in the pterygoid plates. The left pair is more laterally displaced from the midline. Skull vault plagiocephaly is evident with an apparent reduction in the anteroposterior dimension of the anterior cranial fossa. [PMID:2503273]
In a Number 10 Tessier cleft there is an upper central orbital cleft with a cleft of the middle one-third of the upper eyelid, which often results in total ablepharia. The eyebrow is disrupted, being virtually absent medially, whereas the lateral portion angles upward toward the frontal hairline. There may be ocular anomalies, including colobomata of the iris. The skeletal cleft is through the midportion of the supraorbital rim, the adjacent frontal bone, and the orbital roof lateral to the supraorbital nerve. A frontal encephalocele frequently occupies the frontal bony cleft. The palpebral fissure is grossly elongated with an amblyopic eye displaced inferiorly and laterally. There is also a divergent squint of the right eye. The eyebrow is deficient medially and becomes thinned out laterally , where it is contiguous with a broad downward and forward projection of the frontotemporal hairline (this may be seen in both the Number 9 and 10 clefts.) A broad frontal encephalocele bulges forward from the middle one-third of the right forehead, supraorbital ridge, and orbital roof. The bony cleft, through which the frontal encephalocele presents, involves the anterior half of the orbital roof, the supraorbital rim, and two-thirds of the vertical height of the frontal bone lateral to the supraorbital nerve. The bony orbit is inferiorly displaced and widened with the lateral orbital wall shortened and laterally deviated. Similar distortion of the anterior cranial fossa is evident, being broader and more flattened on the affected side. The calvarium above the level of the cleft and the cranial base below is symmetric. [PMID:2503273]
An upper medial orbital cleft produces a cleft of the medial one-third of the upper eyelid that extends through the eyebrow into the frontal hairline. The skeletal element of the cleft in the region of the frontal process of the maxilla may either pass lateral to the ethmoid, through the supraorbital rim, or it may pass through the ethmoidal labyrinth to produce orbital hypertelorism. This cleft usually accompanies the Number 3 cleft. The soft tissue features include a cleft of the medial portion of the upper eyelid, an irregularity in hair orientation at the medial end of the eyebrow, and a long tongue-like projection of the frontal hairline onto the forehead. There is a mild flattening of the frontal process of the maxilla and extensive pneumatization of both the ethmoidal and frontal sinuses, both of which are more prominent on the cleft side. No bony clefting of the supraorbital rim or frontal bone is evident. The cranial base and sphenoid architecture, including the pterygoid processes, are symmetric and normal. [PMID:2503273]
There is a soft tissue cleft medial to the inner canthus with a cleft of the root of the eyebrow. The frontal process of the maxilla is flat and broadened, and the ethmoid labyrinth is increased in tranverse dimension, thereby producing orbital hypertelorism. The cribriform plate is of normal width. The frontal sinus is enlarged. Even though the frontal bone is flattened, bony clefts with encephalocele have not been observed. There is a lateral displacement of the inner canthus with a mild thinning, aplasia, or irregularity of the medial end of the eyebrow. There are no eyelid clefts. The soft tissue contour of the forehead is normal, with only a short downward prolongation of the paramedian frontal hairline to mark the superior extent of the soft tissue cleft. Flattening of the frontal process of the maxilla, an increase in the transverse dimension of the ethmoid sinus, and a laterally convex bowing of the medial orbital wall produce orbital hypertelorism. Superiorly there is a minor flattening of the frontal bone medially, and the nasofrontal angle is somewhat obtuse. The extensive pneumatization of the sinuses on the cleft side extends backward through the frontal and ethmoid sinuses and into the sphenoid sinus. The anatomy of the sphenoid, including the pterygoid processes, is otherwise normal. The anterior and middle cranial fossae floors are both broadened on the cleft side with minor widening of the cribriform plate. [PMID:2503273]
There is a paramedian frontal encephalocele and a soft tissue cleft that passes medial to an intact eyebrow. The frontal bone shows a paramedian bony cleft with an associated encephalocele. The olfactory groove, cribriform plate, and ethmoid sinus are all increased in transverse diameter, resulting in hypertelorism. The cleft extends medially to the undisturbed eyebrow to end in a short paramedian frontal widow's peak. The bony cleft begins in the region of the nasal bone and extends superiorly through the full height of the frontal bone. Posteriorly, the cleft extends through the cribriform plate and ethmoid sinus as far as the lesser wing and body of the sphenoid. The pterygoid processes are anatomically normal, but they are displaced laterally from the midline on the cleft side. There is orbital hypertelorism below and asymmetry of the floor of the anterior cranial fossa above. [PMID:2503273]
A lower midline facial cleft, also known as the median mandibular cleft. It is a rare anomaly, which may be limited to a defect in the soft tissue of the lower lip. However, in the more severe form, it may extend into the bony mandibular symphysis. [PMID:22529554]
A conspicuously unhappy disposition characterized by negative assumptions, self-defeating talk, fear of failure, and negative ruminations about past events. []
An abnormally large Eustachian valve (postnatally). The Eustachian valve is also known as the valve of the inferior vena cava, and is an embryologic remnant of the valve of the inferior vena cava. [PMID:12484622]
An anomaly of the PR interval, which is the portion of the ECG from the end of the P wave to the beginning of the QRS complex. A normal PR interval in adults is from 0.12-0.2 seconds. []
Any anomaly of the P wave of the EKG, which results from atrial depolarization. The P wave occurs when the sinoatrial node creates an action potential that depolarizes the atria. []
An anomaly of the PR segment, which begins at the endpoint of the P wave and ends at the onset of the QRS complex. The PR segment is normally flat and isoelectric. []
P wave below insteadof above the baseline. P-wave inversion in the inferior leads may indicate a non-sinus origin of the P waves. []
An anomaly in the system of mucociliary transport, which functions to transport the mucous layer lining the respiratory epithelium by ciliary nbeating. []
An abnormally increased amount of time required to clear mucus (and substances contained in the mucus) from the nasal mucosa. The nasal mucociliary clearance (NMC) system functions to transport the mucous layer lining the nasal epithelium towards the naso pharynx by ciliary beating in a metachronous fashion at a frequency of 7-16 Hz. NMC depends upon two principal components: physicochemical qualities and quantities of mucus and the properties of cilia that propel it. NMC is considered to be representative of pulmonary clearance. normal NMC time is determined to be up to 20 minutes. Duration of 30 minutes is considered as the cutoff point that discriminates normal subjects from subjects with impaired NMC. NMC can be measured by determination of the transport time of markers that are placed on the nasal mucosa including saccharine, radioactive markers, and dyes. []
A developmental defect characterized by the lack of formation of the carotid canal, which normally is a circular aperture in the temporal bone of the skull through which the internal carotid artery and the carotid plexus of nerves traverse. [PMID:21339912]
Any anomaly of the pigmentation of the fundus, the posterior part of the eye including the retina and optic nerve. []
A type of intraretinal hemorrhage that is located in the superficial retina between the inner limiting membrane and the retinal nerve fiber layer. [PMID:17229799]
Absence of a region of the retina, retinal pigment epithelium, and choroid at the lower part of the fundus. []
A notch or cleft of the lower part of the retina. []
Faint anterior chamber flare. [PMID:16196117]
Moderate anterior chamber flare (iris and lens details clear). [PMID:16196117]
Marked anterior chamber flare (iris and lens details hazy). [PMID:16196117]
Intense anterior chamber flare (fibrin/plastic aqueous). [PMID:16196117]
Absence of the normal opening of a coronary ostium. There are normally two coronary ostia, which are site of origin of the main left or right main coronary artery and are located in the ascending aorta just above the aortic valve. []
Pathological deposition of calcium salts in the globus pallidus. []
Cardiac arrest that would have led to rapid and unexpected death had an intervention not taken place to prevent it. [ORCID:0000-0001-5835-5515, PMID:25187745]
Any structural anomaly located between the pleura and the chest wall. []
So-called honeycombs (variably sized cysts in a background of densely scarred tissue) located in the subpleural space. [PMID:23220902]
Abnormal origin of the right subclavian artery from the descending aorta. The right subclavian artery normally arises from the brachiocephalic trunk, which divides into the right common carotid artery and right subclavian artery. []
The left common carotid artery normally originates from the aortic arch. This term refers to an origin of this artery from the main pulmonary artery. [PMID:27974985]
Absence of the normal opening of the coronary ostium from which the right main coronary artery originates. []
The left anterior descending artery (LAD) branches off from the pulmonary artery. [PMID:27358682]
The left main coronary artery (LMCA) is absent and the left anterior descending (LAD) and left circumflex (LCX) arteries arise from separate but adjacent ostia in the left sinus of Valsava. []
Any structural anomaly of the radial artery. []
An eccentric abnormal localized widening (dilatation) of the ascending tubular aorta that involves only a portion of the circumference of the vessel wall. []
A concentric abnormal localized widening (dilatation) of the abdominal aorta that involves the full circumference of the vessel wall []
A concentric abnormal localized widening (dilatation) of the aortic arch that involves the full circumference of the vessel wall. []
An eccentric abnormal localized widening (dilatation) of the aortic arch that involves only a portion of the circumference of the vessel wall. []
Any functional defect of the mitral or tricuspid valve. []
Any functional defect of the tricuspid valve. []
Any functional abnormality of a cardiac valve. []
Any functional anomaly of the pumonary valve. []
Systolic anterior motion of the mitral valve (SAM) is a paradoxical motion of the anterior, and occasionally posterior, mitral valve leaflet towards the left ventricular outflow tract (LVOT) during systole. [PMID:22847594]
Any anomaly of the second heart sound (S2), which is produced by aortic (A2) and pulmonic (P2) valve closure. The A2-P2 interval normally increases with inspiration and narrows with expiration. []
A type of atrial flutter associated with rounded or bimodal positive deflections in inferior leads II, III and aVF, and a very characteristic bimodal negative wave in the shape of a W is seen in lead V1. [PMID:28835836]
A type of atrioventricular reentrant tachycardia (AVRT) where the are the atrioventricular node is used for anterograde conduction and the accessory pathway for retrograde conduction. [PMID:29234357]
A type of atrioventricular reentrant tachycardia (AVRT) where the are the accessory pathway is used for anterograde conduction and the atrioventricular node for retrograde conduction. []
A ventricular tachycardia (VT) characterized by right bundle branch block (RBBB) and left axis deviation (LAD) on electrocardiogram (ECG). [PMID:29184614]
A lesion associated with atherosclerosis, a multifactorial and multipart progressive disease manifested by the focal development within the arterial wall of lesions, that ranges from teh development of a fatty streak, plaque progression, and plaque disruption. Atherosclerotic lesions demonstrate consistent morphological characteristics, which indicate that each type may stabilize temporarily or permanently and that progression to the next type may require an additional stimulus. [PMID:8172861]
Type I lesions represent the very initial changes and are recognized as an increase in the number of intimal macrophages and the appearance of macrophages filled with lipid droplets (foam cells). []
Type II atherosclerotic lesions include the fatty streak lesion, the first grossly visible lesion, and are characterized by layers of macrophage foam cells and lipid droplets within intimal smooth muscle cells and minimal coarse-grained particles and heterogeneous droplets of extracellular lipid. [PMID:8172861]
Type III (intermediate) atherosclerotic lesions are the morphological and chemical bridge between type II and advanced lesions. Type III lesions appear in some adaptive intimal thickenings (progression-prone locations) in young adults and are characterized by pools of extracellular lipid in addition to all the components of type II lesions. [PMID:8172861]
Type V lesions are defined as lesions in which prominent new fibrous connective tissue has formed. When the new tissue is part of a lesion with a lipid core (type IV), this type of morphology may be referred to as fibroatheroma or type Va lesion. A type V lesion in which the lipid core and other parts of the lesion are calcified may be referred to as type Vb. A type V lesion in which a lipid core is absent and lipid in general is minimal may be referred to as type Vc. With these lesions, arteries are variously narrowed, generally more than with type IV. Importantly, as with type IV lesions, type V lesions may develop fissures, hematoma, and/or thrombus (type VI lesion), and for this reason too they are clinically relevant. []
Type VI atherosclerotic lesions generally have the underlying morphology of type IV or V lesions, surface disruptions, hematoma, and thrombosis may be (although less often) superimposed on any other type of lesion and even on intima without an apparent lesion. Complicating features may arise because of individual differences in risk factors and tissue reactions. These may include differences in composition of the blood, the relative quantities and distributions in the components of the underlying lesion or intima, as well as modifications of shear and tensile forces to which the lesion or intima is exposed. Clinical imaging of lesions may be expected to contribute greatly to the understanding of type VI lesions and the associated clinical syndromes. [PMID:7648691]
An abnormally elevated amount of alpha1-antitrypsin in the feces. []
An unusually severe infection by cytomegalovirus. [PMID:12588074]
An unusually severe Epstein Barr virus (EBV) infection. []
An unusually severe adenovirus infection. [PMID:24678403]
An unusually severe infection by a parainfluenza virus. []
A viral infection that fails to be contained by the immune sytem and spreads throughout the body. [PMID:28476145]
A dissemination viral infection caused by a live attenuated vaccine virus. [PMID:25452596]
Failure to contain infection by a protozoan of the genus Cryptosporidium, leading to spread to many parts of the body. []
A poarasitic infection whereby the parasite invades (migrates through) tissues of the infected host. []
The presence of inflammatory cells in the aqueous humor of the anterior chamber of the eye. []
The presence of erythrocyte in the aqueous humor of the anterior chamber of the eye. []
A tendency to hold the chin depressed (lowered) to compensate for a limitation of eye movement. []
A tendency to turn the face to the right to compensate for a limitation of eye movement. []
A tendency to turn the face to the left to compensate for a limitation of eye movement. []
A tendency to tilt the head towards the right shoulder to compensate for a limitation of eye movement. []
A tendency to tilt the head towards the left shoulder to compensate for a limitation of eye movement. []
An abdominal aortic aneurysm that is not symmetric around its axis (not axisymmetric). [PMID:12751282]
A form of divergent strabismus (exotropia) in which the eye turns outward at all distances and at all times. [ORCID:0000-0003-0986-4123]
A type of exotropia (divergent strabismus) in which binocular single vision alternates with large angle exotropia in rhythmic cycle. [ORCID:0000-0003-0986-4123]
Exotropia (intermittent or constant) on distance fixation with binocular single vision on near fixation under all testing conditions. The accommodative convergence/accommodation (AC:A) ratio is within normal limits. [ORCID:0000-0003-0986-4123]
Exotropia (intermittent or constant) worse for distance fixation in which the near angle of deviation increases (or near exophoria becomes exotropia) with: (1) prolonged disruption of fusion and/or (2) elimination of accommodation. []
A form of hypermetropia with not more that +2.00 diopters. [ORCID:0000-0003-0986-4123]
A form of hypermetropia with more than +2.00 diopters but not more than +5.00 diopters. [ORCID:0000-0003-0986-4123]
Increased lacrimation owing to overproduction of tears. [ORCID:0000-0003-0986-4123]
A form of watery eye associated with overproduction of tears due to an increased parasympathetic drive to the secretory component of the lacrimal system (lacrimal gland); this could be due to pro-secretory drug use (e.g. pilocarpine) or autonomic disturbance. [ORCID:0000-0003-0986-4123]
A form of watery eye associated with overproduction of tears due to reflex tearing in response to a local irritant (e.g. trichiasis or foreign body), chronic ocular surface disease (e.g. blepharitis) or systemic disease (e.g. thyroid eye disease). [ORCID:0000-0003-0986-4123]
A form of watery eye associated with abnormal lid tone and/or lid position. The former is due to lid laxity (common involutional change in the elderly) or a weak orbicularis muscle (e.g. due to VII cranial nerve palsy). The latter is typically associated with ectropion causing punctal eversion. [ORCID:0000-0003-0986-4123]
A functional anomaly of the inferior or superior oblique muscle. [ORCID:0000-0003-0986-4123]
A functional anomaly of the medial rectus muscle or lateral rectus muscle. []
Reduced ocular movement by the inferior oblique muscle which improves on testing ductions, typically associated with neurogenic palsy. [ORCID:0000-0003-0986-4123]
Reduced movement by the inferior rectus muscle which improves on testing ductions, typically associated with neurogenic palsy. [ORCID:0000-0003-0986-4123]
Excessive action of the inferior rectus muscle caused by increased innervation typically as a consequence of palsy or limitation to the ipsilateral antagonist or contralateral synergist. [ORCID:0000-0003-0986-4123]
Decreased strength of the superior rectus muscle. []
Excessive action of the superior rectus muscle caused by increased innervation typically as a consequence of palsy or limitation to the ipsilateral antagonist or contralateral synergist. [ORCID:0000-0003-0986-4123]
Mechanical limitation of the range of movement of the superior rectus muscle. [ORCID:0000-0003-0986-4123]
A functional anomaly of the superior or inferior rectus muscle. [ORCID:0000-0003-0986-4123]
A functional anomaly of the lateral rectus muscle. []
Decreased strength (ability to move) of the lateral rectus muscle. [ORCID:0000-0003-0986-4123]
Reduced movement of the lateral rectus muscle which improves on testing ductions, typically associated with neurogenic palsy. [ORCID:0000-0003-0986-4123]
Excessive action of the lateral rectus muscle caused by increased innervation typically as a consequence of palsy or limitation to the ipsilateral antagonist or contralateral synergist. []
Decreased strength of the medial rectus muscle. [ORCID:0000-0003-0986-4123]
Excessive action of the medial rectus muscle caused by increased innervation typically as a consequence of palsy or limitation to the ipsilateral antagonist or contralateral synergist. []
A functional anomaly of a vertical or horizontal rectus muscle. [ORCID:0000-0003-0986-4123]
Reduced movement of the medial rectus muscle which improves on testing ductions, typically associated with neurogenic palsy. [ORCID:0000-0003-0986-4123]
Mechanical limitation of the range of movement of the lateral rectus muscle. []
A form of convergent strabismus (esotropia) in which the deviation is present under all conditions (ie at all distances and at all times). [ORCID:0000-0003-0986-4123]
A form of esotropia in which the angle of deviation is not affected by accommodative effort. [ORCID:0000-0003-0986-4123]
Esotropia in which normal binocular single vision is present for all distances when the hypermetropic refractive error is corrected. Esotropia is present for near and distance on accommodation without correction. [ORCID:0000-0003-0986-4123]
A form of constant esotropia in which the angle of deviation is partially affected by accommodative effort. Typically there is esotropia at near and distance with hypermetropic correction and the angle of deviation increases without glasses. [ORCID:0000-0003-0986-4123]
Fixation of an object in the area adjacent to the fovea. [ORCID:0000-0003-0986-4123]
Fixation of an object in a peripheral area of the retina. [ORCID:0000-0003-0986-4123]
Any structural anomaly of the posterior circulating artery (PCOM). []
A funnel-shaped symmetrical enlargement of the origin of the posterior communicating artery at its junction with the internal carotid artery. [PMID:9848859]
A type of ascites in which there are large numbers of eosinophils in the ascitis fluid. [PMID:27721930]
A type of microtropia with no manifest movement on cover test, the eccentric fixation point coinciding with the angle of ARC. [ORCID:0000-0003-0986-4123, PMID:9602615]
A type of microtropia in which the manifest movement is demonstrated on the cover-uncover test. [ORCID:0000-0003-0986-4123, PMID:9602615]
Any structural anomaly of the portion of the aorta that arises from the base of the left ventricle and extends upward to the aortic arch and from which the coronary arteries arise. [MP:0009867]
An abnormality in voluntary or involuntary eyelid movements or their control. []
An increased concentration of leptin in the blood. [RGD:sjwang]
A decrease below the normal concentration of glycerol in the blood. []
Any deviation from the normal concentration of glycerol in the blood. []
Increased circulating level of apolipoprotein B, which is the main apolipoprotein of chylomicrons and low density lipoproteins. It occurs in plasma as two main isoforms, apoB-48 and apoB-100. [ORCID:0000-0001-5356-4174]
Reduced criculating level of apolipoprotein AI, which is the major protein component of high density lipoprotein (HDL) in plasma. Defects in this gene are associated with HDL deficiencies, including Tangier disease. [ORCID:0000-0001-5356-4174]
An increased concentration in blood of apolipoprotein A-II, a major component of HDL particles, associated with triglyceride and glucose metabolism. [ORCID:0000-0001-5356-4174]
Shortening of the fourth and fifth metacarpals when the fist is clenched. [Gene42:pbuczkowicz, PMID:22075011, PMID:22629539]
An excess of eosinophilic cells in colonic tissue, i.e., eosinophilic infiltration in the colon. [PMID:21922029]
A functional anomaly of the mouth (which is also known as the oral cavity). []
Any structural anomaly of the mouth, which is also known as the oral cavity. []
A deviation from normal of the waist to hip ratio, defined as the waist measurement divided by hip measurement. []
Increased waist-to-hip ratio (WHR) is a measurement above the average for the dimensionless ratio of the circumference of the waist to that of the hips. WHR is calculated as waist measurement divided by hip measurement. [ORCID:0000-0001-5356-4174, PMID:12872269]
Decreased waist-to-hip ratio (WHR) is a measurement below the average for the dimensionless ratio of the circumference of the waist to that of the hips. WHR is calculated as waist measurement divided by hip measurement. [PMID:12872269, RGD:gthayman]
Altered level of the enzyme that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate. [RGD:sjwang]
Abnormally increased level of the enzyme that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate. [RGD:sjwang]
Abnormally decreased level of the enzyme that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate. [RGD:sjwang]
Liver mast cell infiltration. [HPO:probinson, PMID:25009756]
An anomaly of a reflex that is elicited as a motor response to scraping of the skin. They are generally graded as present or absent. They differ from tendon reflexes in that the sensory signal must ascend the spinal cord to reach the brain and then descend the spinal cord to reach the motor neurons. []
An increasedreduced concentration of zinc in the blood. [PMID:16518702, RGD:gthayman]
Overshoot of downward saccadic eye movements. []
Saccadic undershoot of upward saccadic eye movements, i.e., an upward saccadic eye movement that has less than the magnitude that would be required to gain fixation of the object. []
Small ectopic arteries or arterial branches that connect the aorta, aortic branches and/or subclavian artery regions directly to the lung parenchyma, usually seen in conjunction with pulmonary atresia, ventricular septal defect (VSD) and/or closed ductus arteriosus. [MP:0010635, PMID:26467877]
An abnormal level of catalysis of the reaction: 2 superoxide + 2 H+ = O2 + hydrogen peroxide. [PMID:25276767, RGD:gthayman]
Increased catalysis of the reaction: 2 superoxide + 2 H+ = O2 + hydrogen peroxide. [RGD:gthayman]
Decreased catalysis of the reaction: 2 superoxide + 2 H+ = O2 + hydrogen peroxide. [PMID:25276767, RGD:gthayman]
Presence of a chemical substance found within an individual that is not naturally produced or expected to be present in human tissues or bodily fluids. []
The presence of a xenobiotic in urine. []
Any deviation from the normal sexual drive or desire for sexual activity. []
Reduced ability to walk (ambulate) in a backwards direction. [HPO:probinson]
An abnormality of gait that can be observed in individuals with dystonic posture in which the individual walks with an extended trunk and flexed arms, while strutting on the toes without the heels touching the floor. [PMID:24746291]
A reversal of sleeping habits with a tendency to sleep during the day and to be awake at night. []
A type of heterotaxy where some paired structures on opposite sides of the left-right axis of the body are symmetrical mirror images of each other, and have the morphology of the normal left-sided structures. [PMID:21731561]
An abnormal gait characterized by toe walking, stiff legs, and skipping. The gait pattern has some resemblance to cock-walk gait, but in affected individuals are able tonimprove their dystonic gait by walking backward. [PMID:21956287]
Reduced or inadequate esophageal peristalsis, with resultant slow passage of contents through the esophagus. []
Longitudinal grooves in the surface of the esophagus arranged in a longitudinal fashion (from top to bottom of the esophagus). [PMID:25368745]
Any abnormality in the variability of the time interval between successive heartbeats. [PMID:8598068]
Reduced variation of beat-to-beat intervals of the heart that occurs in conjunction with the respiratory cycle. [ORCID:0000-0001-5356-4174, PMID:8598068]
Increased variation of beat-to-beat intervals of the heart that occurs in conjunction with the respiratory cycle. [ORCID:0000-0001-5356-4174, PMID:8598068]
Any functional anomaly of the liver. [HPO:probinson]
Increased passive stiffness or tightness of the neck musculature. []
Difficulty reaching to visually guided goals in peripheral vision, with the deficit leaves voluntary eye movements largely unaffected. [ORDIC:0000-0002-6601-2165, PMID:24607223]
Any functional anomaly of Langerhans cells, which are dendritic cells in the epidermis and some other locations. Langerhans cells play roles iin immune surveillance and homeostasis. [PMID:29449841]
Birbeck granules (BG) are cytoplasmic organelles that are only found in Langerhans cells (LC). The function of BG is still not completely understood, although most studies point toward an active role in receptor-mediated endocytosis and participation in the antigen-processing/presenting function of LC. This feature refers to the absence of BG in LC, a feature that can be documented by means of electron microscopy. [HPO:probinson, PMID:15816828]
A tendency towards rising very early in the morning and going to bed early in the evening. []
A tendency towards rising very late in the morning and going to bed late at night. []
Any deviation from the normal concentration of hepcidin in the blood circulation. [HPO:probinson, PMID:16450011]
An abnormally reduced concentration of hepcidin in the blood circulation. [HPO:probinson, PMID:16450011]
An abnormally increased concentration of hepcidin in the blood circulation. [HPO:probinson, PMID:16450011]
Any functional abnormality of the eyelid. []
A form of watery eye associated with obstruction of the nasolacrimal system. This may arise at the level of the punctum, the canaliculi, the sac or the nasolacrimal duct. [UManchester:psergouniotis]
An elevated concentration of proinsulin (the prohormone precursor to insulin) to mature insulin in the circulation. [RGD:gthayman]
A deviation from normal concentration of glucose content in the cerebrospinal fluid. []
Abnormally high glucose concentration in the cerebrospinal fluid. [HPO:nvasilevsky]
Any deviation from the normal concentration of low-density lipoprotein cholesterol in the blood circulation. [HPO:probinson]
Any deviation from the normal circulating concentration of chylomicrons. []
Any deviation from the normal concentration of high-density lipoprotein cholesterol (HDL) in the blood. []
Any deviation from the normal concentration of very-low-density lipoprotein cholesterol in the blood. []
Any deviation from the activity of coagulation factor V. []
Any deviation from the normal circulating concentration of mast cell beta-tryptase concentration. [HPO:probinson, PMID:15200544]
An abnormally elevated circulating concentration of mast cell beta-tryptase concentration. []
Any deviation from the normal circulating concentration of selenium. [HPO:probinson, PMID:26045617, PMID:29494512]
Any deviation from the normal total hemolytic complement activity in the circulation. []
An abnormally elevated total hemolytic complement activity in the circulation. [HPO:probinson]
An abnormally reduced total hemolytic complement activity in the circulation. [HPO:probinson]
A decrease in the level of 1,5 anhydroglucitol in the serum. 1,5-Anhydrosorbitol is a validated marker of short-term glycemic control. This substance is derived mainly from food, is well absorbed in the intestine, and is distributed to all organs and tissues. [PMID:16731998, PMID:17659063, PMID:9357814]
An increase in the level of allantoin in the serum. [PMID:18636793]
An increase in the level of GABA in the serum. [PMID:1485027]
A decrease in the level of GABA in the serum. [PMID:1485027]
A decrease in the level of erythritol in the urine. [PMID:14988808]
A decrease in the level of erythritol in the cerebrospinal fluid. [PMID:14988808]
An increase in the level of D-threitol in the plasma. [PMID:14988808]
An increase in the level of D-threitol in the cerebrospinal fluid. [PMID:14988808]
An increase in the level of D-threitol in the urine. [PMID:14988808]
A decrease in the level of D-mannose in the urine. [PMID:29099052]
An increase in the level of galactitol in the plasma. [PMID:11092512, PMID:7671965]
An increase in the level of galactitol in the urine. [PMID:11092512, PMID:7671965]
An increase in the level of galactonate in the red blood cells. [PMID:14680973]
An increase in the level of galactitol in the red blood cells. [PMID:14680973]
An increase in the level of hippuric acid in the blood. [PMID:22626821]
An increase in the level of hippuric acid in the urine. [PMID:19551947, PMID:22626821]
An increase in the level of L-fucose in the urine. [PMID:2311216]
An increase in the level of L-glutamic acid in the blood. [PMID:7623444]
An increase in the level of propylene glycol in the blood. [PMID:3426740]
An increase in the level of ribitol in the urine. [PMID:14988808]
An increase in the level of ribitol in the cerebral spinal fluid. [PMID:14988808]
An increase in the level of ribose in the urine. [PMID:14988808]
An increase in the level of ribose in the cerebrospinal fluid. [PMID:14988808]
An increase in the level of xylitol in the urine. [PMID:14988808]
An increase in the level of xylitol in the cerebrospinal fluid. [PMID:14988808]
An increase in the level of L-pyroglutamic acid in the urine. [PMID:10094443, PMID:4557757]
An abnormality in biotinidase activity, an enzyme that releases biotin from biocytin, the product of biotin-dependent carboxylases degradation. [PMID:29359854]
A decrease in biotinidase activity, an enzyme that releases biotin from biocytin, the product of biotin-dependent carboxylases degradation. [PMID:29359854]
An increase in biotinidase activity, an enzyme that releases biotin from biocytin, the product of biotin-dependent carboxylases degradation. [PMID:29359854]
Infiltration of numerous eosinophils (usually greater than 15 per high power field) into the squamous epithelium of the esophagus, and layering of eosinophils on the surface layer of the esophagus. [PMID:27158535]
The formation of small localized collection of eosinophiles (an eosinophilic microabscess) in the esophagus. Usually clusters of greater than or equal to 4 eosinophils are seen, that appear as exudates or white spots or white plaques. [PMID:27158535]
An increase in the level of methylsuccinic acid in the urine. [PMID:16828325, PMID:19343532, PMID:3571488, PMID:6616873]
An increase in the level of myristic acid in the serum. [PMID:22024767]
An increase in the level of N-acetylneuraminic acid in the urine. [PMID:7398077]
An increase in the level of N-acetylneuraminic acid in cultured fibroblasts. [PMID:11992753]
An increase in the level of O-phosphoethanolamine in the urine. [PMID:23093139]
A defect in the of the process of interstrand cross-link repair: removal of a DNA interstrand crosslink (a covalent attachment of DNA bases on opposite strands of the DNA) and restoration of the DNA. DNA interstrand crosslinks occur when both strands of duplex DNA are covalently tethered together (e.g. by an exogenous or endogenous agent), thus preventing the strand unwinding necessary for essential DNA functions such as transcription and replication. [GO:0036297, PMID:16464006, PMID:22064477]
Any abnormality of the chest muscles. []
Any abnormality of the shoulder muscles. []
Increased concentration of cotinine in the urine. []
The presence of a xenobiotic in blood. []
An increased concentration of tropnin I in the blood, which is a cardiac regulatory protein that controls the calcium mediated interaction between actin and myosin. Raised cardiac troponin concentrations are now accepted as the standard biochemical marker for the diagnosis of myocardial infarction. []
An increased concentration of tropnin T in the blood, which is a cardiac regulatory protein that controls the calcium mediated interaction between actin and myosin. Raised cardiac troponin concentrations are now accepted as the standard biochemical marker for the diagnosis of myocardial infarction. [PMID:15452153]
An anomaly in the level of glucose-6-phosphate dehydrogenase. []
An anomaly in the level of glucose-6-phosphate dehydrogenase in the blood. [PMID:24787449]
An increase in the level of glucose-6-phosphate dehydrogenase in the blood. []
A decrease in the level of glucose-6-phosphate dehydrogenase in the blood. [PMID:24787449]
An anomaly in the level of glucose-6-phosphate dehydrogenase in a dried blood spot. [PMID:28479150]
An increase in the level of glucose-6-phosphate dehydrogenase in a dried blood spot. [PMID:28479150]
A decrease in the level of glucose-6-phosphate dehydrogenase in a dried blood spot. [PMID:28479150]
An anomaly in the level of glucose-6-phosphate dehydrogenase in leukocytes. [https://doi.org/10.1016/B978-0-12-383834-6.00086-0]
An anomaly in the level of glucose-6-phosphate dehydrogenase in red blood cells. [PMID:18942156]
An anomaly in the level of glucose-6-phosphate dehydrogenase in tissue. []
An increase in the level of glucose-6-phosphate dehydrogenase in tissue. []
A decrease in the level of glucose-6-phosphate dehydrogenase in tissue. []
A decrease in the level of glucose-6-phosphate dehydrogenase in red blood cells. [PMID:18942156]
An increase in the level of glucose-6-phosphate dehydrogenase in red blood cells. []
A decrease in the level of glucose-6-phosphate dehydrogenase in leukocytes. [https://doi.org/10.1016/B978-0-12-383834-6.00086-0]
An increase in the level of glucose-6-phosphate dehydrogenase in leukocytes. []
An abnormality in uridine diphosphate glucose-4-epimerase activity, an enzyme that catalyzes the reaction: UDP-glucose = UDP-galactose. []
An abnormality in uridine diphosphate glucose-4-epimerase activity in plasma. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose. []
An increase in uridine diphosphate glucose-4-epimerase activity in plasma. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose. []
A decrease in uridine diphosphate glucose-4-epimerase activity in plasma. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose. []
An abnormality in uridine diphosphate glucose-4-epimerase activity in red blood cells. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose. []
An increase in uridine diphosphate glucose-4-epimerase activity in red blood cells. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose. []
A decrease in uridine diphosphate glucose-4-epimerase activity in red blood cells. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose. []
Any abnormality in the proportion natural killer subsets relative to the total number of natural killer cells. []
Blockage of the nasolacrimal sac. [PMID:17203310]
A mass of granulation tissue in response to chronic dacryocystitis as polypoid formations or they follow accidental injury, from probing and as a reaction to retained foreign bodies in the sac. [PMID:13434546]
Benign tumor of the nasolacrimal sac. [PMID:4352147]
The malignant epithelial neoplasm with papillary growths in the nasolacrimal sac. [PMID:16253035]
An abnormality of the conjuctiva and ocular surface caused by conjunctival inflammation and associated with scarring. [ORCID:0000-0003-0986-4123]
A unilateral or bilateral eyelid retraction due to midbrain lesions. [PMID:17323781]
A type of lymphoma that involves the nasolacrimal sac. [ORCID:0000-0003-0986-4123, PMID:9392338]
A very common condition in which the extreme end of the nasolacrimal duct underneath the inferior turbinate fails to complete its canalization in the newborn period. [PMID:11222337]
A detachment that involves the peripheral retina that does not extend into the macula. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
A detachment that involves the peripheral retina that involves the macula itself. The detachment usually starts in the temporal periphery although can also involve the nasal retina as well. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
An open funnel detachment of the retina with generally traction in all four quadrants. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
A closed funnel detachment of the retina with generally traction in all four quadrants. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
Retinopathy which extends from the center of the optic disc to twice the distance from the center of the optic disc to the center of the macula. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham, PMID:16009843]
Retinopathy which extends centrifugally from the edge of zone I to the nasal ora serrata. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham, PMID:16009843]
Retinopathy which is a residual crescent of retina anterior to zone II. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham, PMID:16009843]
Venous dilatation and arteriolar tortuosity of the posterior retinal vessels and may later increase in severity to include iris vascular engorgement, poor pupillary dilatation (rigid pupil), and vitreous haze. This definition has been further refined in the later clinical trials in which the diagnosis of plus disease could be made if sufficient vascular dilatation and tortuosity are present in at least 2 quadrants of the eye. [PMID:16009843]
As vascular abnormalities of the posterior pole that are insufficient for the diagnosis of plus disease but that demonstrate more arterial tortuosity and more venous dilatation than normal. [PMID:16009843]
A retinopathy with a 50% likelihood of progressing to retinal detachment. Threshold disease is considered to be present when stage 3 retinopathy of prematurity (ROP) is present in either zone I or zone II, with at least 5 continuous or 8 total clock hours of disease, and the presence of plus disease. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
High risk patients who were in Zone 1 (no Plus or stage 3) or Zone 2 with Plus or stage 3 but not both. [Lee T. (2017) Classification of ROP. In: Kychenthal B. A., Dorta S. P. (eds) Retinopathy of Prematurity. Springer, Cham]
The difference between total and manifest myopia. [ORCID:0000-0003-0986-4123]
A conjuctival lesion composed of adipose tissue and dense connective tissue. Such choristomas of dermal elements are normally found at the outer canthus, and have a gelatinous appearance. Classically, there is an indistinct posterior border (with the lesion frequently extending into the orbit) and a well-demarcated anterior border several millimetres posterior to the limbus. [ORCID:0000-0003-0986-4123]
Eccentric fixation in which the angle of eccentricity equals the objective angle of deviation. [ORCID:0000-0003-0986-4123]
Any deviation from the normal ocular alignment. [ORCID:0000-0001-7941-2961]
A type of vertical tropia in which, when one eye is fixing, the other eye is deviated upwards. [ORCID:0000-0003-0986-4123]
A type of vertical tropia in which, when one eye is fixing, the other eye is deviated downwards. [ORCID:0000-0003-0986-4123]
A type of vertical phoria in which, in dissociation, the occluded eye deviates downwards. [ORCID:0000-0003-0986-4123]
Having a characteristic appearance of a slate gray area of pigmentation within the disc margins that commonly appears along the inferotemporal or temporal neuroretinal rim areas. [PMID:24862768]
Loss of pigment in the fovea centralis. [PMID:24023426]
A capillary hemangioma surrounding the eyeball but within the orbit. [PMID:20616917]
A mesenchymal tumour that is considered to be the commonest primary orbital malignancy in children. Histologically, it may be differentiated into embryonal, alveolar, and pleomorphic types. It is usually intraconal or within the superior orbit. []
Presence of a xenobiotic in meconium. []
Presence of a xenobiotic in plasma and/or serum. []
Presence of a xenobiotic in gastric fluid. []
A compensatory head posture occurs when the head is deviated out of the normal primary straight head position in order to compensate for an ocular problem. []
Reduced movement of the superior rectus muscle which improves on testing ductions, typically associated with neurogenic palsy. [ORCID:0000-0003-0986-4123]
Clasp-knife phenomonen refers to increased muscle tone while bending or stretching a limb, whereby there is a sudden relaxtion (decrease in resistance) as the muscle continues to be streched. This phenomenon has been likened to opening a clasp knife. [HPO:probinson]
Any structural anomaly of a cell of the monocyte, granulocyte, mast cell, megakaryocyte, or erythroid lineage. []
The right common carotid artery normally originates from the brachiocephalic artery. This term refers to an origin of this artery directly from the aorta. [PMID:12601459]
An abnormally reduced circulating concentration of mast cell beta-tryptase concentration. []
Pharmacologic agents that block NOCICEPTIVE PAIN signaling from CALCITONIN GENE-RELATED PEPTIDE RECEPTORS. They may be useful for the treatment of pain associated with MIGRAINE DISORDERS and OSTEOARTHRITIS.
Hormones and molecules with calcium regulating hormone-like actions that modulate OSTEOLYSIS and other extra-skeletal activities to maintain calcium homeostasis.
Mostly benign fibro-osseous proliferation of the facial bone and skull. It can be either monostotic (localized to a single bone) or polyostotic (localized to more than one bone) type.
Symptom of underactive detrusor muscle of the URINARY BLADDER that contracts with abnormally reduced strength or duration resulting in an incomplete and/or prolonged bladder emptying.
A topical preparation of tobramycin and dexamethasone that is used for treating or preventing superficial bacterial infections of the eye.
Substances that stimulate the secretion of another substance.
Drugs formulations that do not meet established standards.
Agents used in the treatment of ECHINOCOCCOSIS, especially those that kill the hydatid cyst, or larvae, of ECHINOCOCCUS worms.
Systemic infection during pregnancy, child-birth, post-abortion, or post-partum period often associated with organ dysfunction.
Drugs whose formulation does not agree with the information stated on the packaging.
A rare chromosomal anomaly syndrome caused by partial duplication of the long arm of chromosome 20. The disorder has characteristics of psychomotor and developmental delay, moderate intellectual disability, metopic ridging/trigonocephaly, short hands and/or feet and distinctive facial features (epicanthus, hypoplastic supraorbital ridges, horizontal/downslanting palpebral fissures, small nose with depressed nasal bridge and anteverted nostrils, prominent cheeks, retrognathia and small, thick ears). Growth delay and cryptorchidism are often associated features.
A rare chromosomal anomaly syndrome, resulting from the partial deletion of the long arm of chromosome 2, with a highly variable phenotype typically characterised by severe intellectual disability, moderate to severe developmental delay (particularly speech), feeding difficulties, failure to thrive, hypotonia, thin, sparse hair, various dental abnormalities and cleft/high-arched palate. Typical dysmorphic features include high, prominent forehead, down-slanting palpebral fissures and prominent nasal bridge with beaked nose. Various behavioural problems (e.g. hyperactivity, chaotic/repetitive behaviour, touch avoidance) are also associated.
A rare genetic multiple congenital anomaly syndrome with characteristics of atrioventricular septal defects and blepharophimosis, in addition to radial (e.g. aplastic radius, shortened ulna, fifth finger clinodactyly, absent first metacarpal and thumb) and anal (e.g. imperforate or anteriorly placed anus, rectovaginal fistula) defects.
A type of hereditary spastic paraplegia with usual characteristics of pure phenotype of proximal weakness of the lower extremities with spastic gait and brisk reflexes, with a bimodal age of onset of either childhood or adulthood (more than 30 years). In some cases, it can present as a complex phenotype with additional associated manifestations including peripheral neuropathy, bulbar palsy (with dysarthria and dysphagia), distal amyotrophy, and impaired distal vibration sense.
A pure form of hereditary spastic paraplegia with onset in adolescence or early adulthood of slowly progressive spastic paraplegia, proximal muscle weakness of the lower extremities and small hand muscles, hyperreflexia, spastic gait and mild urinary compromise.
A pure form of hereditary spastic paraplegia with characteristics of slowly progressive spastic paraplegia of lower extremities with an age of onset ranging from childhood to adulthood and patients presenting with spastic gait, increased tendon reflexes in lower limbs, extensor plantar response, weakness and atrophy of lower limb muscles and, in rare cases, pes cavus. No abnormalities are noted on magnetic resonance imaging.
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis with characteristics of normal early development followed by the sudden onset in infancy of poor feeding, dysphagia, truncal (followed by global) hypotonia, motor regression, abnormal movements (i.e. severe dystonia of limbs, choreoathetosis, facial dyskinesia) and reduced tendon reflexes. The disease course is severe but nonprogressive.
A rare genetic bone disorder with the presence of two non-fused talar bone fragments, with the posterior fragment located at the level of the posterior talar process. Patients may present with foot and/or ankle pain (exercise-induced or not), repetitive ankle sprains, chronic ankle ligamentous laxity, restricted ankle motion (i.e. plantar flexion, eversion, and inversion), and mild swelling.
A rare benign cutaneous neoplasm containing keratinised epithelium and dermal derivatives, such as hair follicles, sweat and sebaceous glands, smooth muscle or fibroadipose tissue which usually manifests as a slow-growing, painless mass in the submandibular or sublingual space. Depending on the location, and especially after sudden enlargement, it can cause dyspnoea, dysphagia or dysphonia.
A rare genetic bone development disorder with characteristics of proportionate short stature, nail dysplasia (enlarged, convex, hypertrophic nails), hypodontia and night blindness. Osteopenia, a tendency to present fractures, talipes varus with abnormal gait, ear infections, and watering eyes due to narrow tear ducts are frequently associated. Radiologically presents with delayed bone age on wrist X-rays, platyspondyly, and broad metaphyses of humeri with dense and thickened growth plates.
A rare demyelinating hereditary motor and sensory neuropathy characterised by early-onset, slowly progressive, distal muscular weakness and atrophy with no sensory impairment, congenital sensorineural deafness and mild intellectual disability (with absence of normal speech development). The absence of large myelinated fibres on sural nerve biopsy is equally characteristic of the disease.
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis with onset in infancy or early childhood of muscular hypotonia, gait ataxia, mild bilateral pyramidal tract signs, developmental delay (affecting mostly speech and coordination) and subsequent intellectual disability. Short stature, obesity, microcephaly, strabismus, nystagmus, reduced visual acuity, lactic acidosis, and a brain neuropathology consistent with Leigh syndrome are also reported. Caused by homozygous or compound heterozygous mutation in the MTFMT gene on chromosome 15q22.
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis with a variable phenotype that includes onset in infancy or early childhood of failure to thrive and psychomotor regression (after initial normal development), as well as ocular manifestations (such as ptosis, nystagmus, optic atrophy, ophthalmoplegia and reduced vision). Additional manifestations include bulbar paresis with facial weakness, hypotonia, difficulty chewing, dysphagia, mild dysarthria, ataxia, global muscle atrophy, and areflexia. It has a relatively slow disease progression with patients often living into the third decade of life.
A rare mitochondrial disease due to a defect in mitochondrial protein synthesis characterised by initially normal growth and development followed by the infantile-onset of failure to thrive, psychomotor delay, poor feeding, dyspnoea, severe hypertrophic cardiomyopathy and hepatomegaly. Laboratory studies report increased plasma lactate and alanine, abnormal liver enzymes and decreased activity of mitochondrial respiratory chain complexes I, III, IV, and V. Caused by compound heterozygous mutation in the MRPL3 gene on chromosome 3q22.
A rare mitochondrial disease characterised by axial hypotonia with limb hypertonia, developmental delay, hyperlactataemia, central nervous system anomalies visible on magnetic resonance imaging (e.g. corpus callosum hypoplasia, lesions of the globus pallidus) and multiple deficiencies of the mitochondrial respiratory chain complexes in muscle tissue, but not in fibroblasts or liver.
A disorder of lipid absorption and transport characterised by steatorrhoea with foul-smelling stools from birth, diminished serum carotene and vitamin E and a combined deficiency of the pancreatic enzymes lipase and colipase. Patients are otherwise healthy and develop normally with no apparent pancreatic disease. There have been no further descriptions in the literature since 1990.
A rare maxillofacial disorder with characteristics of significant reduction in mouth opening in the absence of acquired factors (e.g. trauma, infection) contributing to the ankylosis. It is associated with variable degrees of facial dysmorphism (i.e. lateral deviation of the mandible and chin, lower facial asymmetry, retrognathia, micrognathia, dental malocclusion) and patients typically present with feeding and breathing difficulties. Developmental delay, hypotonia, seizures, and additional dysmorphic features (e.g. pectus excavatum, low-set ears, hypoplastic alae nasi) have also been reported.
A rare neuro-ophthalmological disorder characterised by a congenital sensory deficit involving all or some of the sensory components of the trigeminal nerve. Due to corneal anaesthesia, it usually presents with recurrent, painless eye infections, painless corneal opacities and/or poorly healing, ulcerated wounds on the facial skin and mucosa (typically the buccal mucosa and/or nasal septum).
A rare benign cutaneous neoplasm containing keratinised epithelium and dermal derivatives, such as hair follicles, sweat and sebaceous glands, smooth muscle or fibroadipose tissue, which usually manifests as a firm, nonpulsatile mass, often with a sinus opening or a hair-bearing punctum, most commonly located in the periorbital and nasal area.
A rare chromosomal anomaly resulting from the partial duplication of the long arm of chromosome 2. The disorder has characteristics of moderate psychomotor delay, mild intellectual disability, facial dysmorphism (high hairline, prominent forehead, hypertelorism, upslanting palpebral fissures, large, low-set and/or posteriorly rotated ears, depressed/broad nasal bridge, prominent nasal tip, thin upper lip vermillion), clino/camptodactyly and normal or increased body measurements. On occasion genital anomalies (hypospadias, cryptorchidism, shawl scrotum) and short stature may be observed.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 4. The disorder has a highly variable phenotype with typical characteristics of psychomotor delay, intellectual disability, craniofacial dysmorphism (microcephaly, low-set, prominent ears, downslanting palpebral fissures, hypertelorism, epicanthic folds, broad, prominent nasal bridge, high arched and cleft palate, micro/retrognathia), seizures, tooth and digital anomalies (clinodactyly, polydactyly). Cardiac malformations, renal anomalies, cryptorchidism, hypotonia and hearing impairment have also been reported.
A rare chromosomal anomaly syndrome resulting from a partial duplication of the long arm of chromosome 5. The disorder has characteristics of short stature, moderate intellectual disability, craniofacial dysmorphism (microcephaly, flat facies, large, low-set dysplastic ears, down-slanted, almond-shaped palpebral fissures, hypertelorism, epicanthal folds, small nose, long philtrum, small mouth with thin upper lip, and micrognathia). Patients also frequently present speech and cognitive delay, cardiac (ventriculomegaly, ventricular septum defect) and skeletal abnormalities (craniosynostosis, radial agenesis, ulnar hypoplasia, brachydactyly) and genital malformations (hypospadias, cryptorchidism).
A rare chromosomal anomaly syndrome resulting from the partial duplication of the short arm of chromosome 7. The disorder has a highly variable phenotype with typical characteristics of severe to profound psychomotor delay, intellectual disability, dysmorphic features (including dolichocephaly, microbrachycephaly, high and/or broad forehead, hypertelorism, downslanting palpebral fissures, low-set, dysplastic ears, low, broad and prominent nasal bridge, abnormal palate, micro/retrognathia) and hypotonia. Cardiovascular, gastrointestinal, skeletal and urogenital anomalies have commonly been reported.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 8. The disorder has a highly variable phenotype with typical characteristics of growth and developmental delay, intellectual disability, short stature, craniofacial dysmorphism (microcephaly, prominent forehead, hypertelorism, abnormal palpebral fissures, low-set, large ears, anteverted tip of nose, micro/retrognathia), congenital heart defects, skeletal and limb anomalies. Other reported features include ophthalmologic abnormalities (e.g. megalocornea), cryptorchidism, hypertrichosis, and neurologic manifestations (e.g. hypotonia, hearing loss and seizures).
A rare genetic developmental defect during embryogenesis with characteristics of severe psychomotor delay, intellectual disability, congenital, symmetrical circumferential skin creases of arms and legs, cleft palate, and facial dysmorphism (including elongated face, high forehead, blepharophimosis, short palpebral fissures, microphthalmia, microcornea, epicanthic folds, telecanthus, microtia, posteriorly angulated ears, broad nasal bridge, microstomia and micrognathia). Additional features reported include short stature, microcephaly, hypotonia, pectus excavatum, severe scoliosis, hypoplastic scrotum and mixed hearing loss.
A rare mitochondrial disease due to a defect in coenzyme Q10 biosynthesis that manifests with a broad spectrum of signs and symptoms which may include: neonatal lactic acidosis, global developmental delay, tonus disorder, seizures, reduced spontaneous movements, ventricular hypertrophy, bradycardia, renal tubular dysfunction with massive lactic acid excretion in urine, severe biochemical defect of respiratory chain complexes II/III when assayed together and deficiency of coenzyme Q10 in skeletal muscle. Cerebral and cerebellar atrophy can be seen on magnetic resonance imaging and multiple choroid plexus cysts and symmetrical hyperechoic signal alterations in basal ganglia have been observed on ultrasound.
A subtype of acute myeloid leukaemia with recurrent genetic abnormalities characterised by clonal proliferation of myeloid blasts harbouring mutations of the NPM1 gene in the bone marrow, blood and other tissues. It is associated with multilineage dysplasia, involving the myeloid, monocytic, erythroid, and megakaryocytic cell lineages. Patients usually present with leukocytosis, thrombocytosis and nonspecific symptoms related to ineffective haematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain), with frequent extramedullary involvement typically presenting as gingival hyperplasia and lymphadenopathy.
A rare neurologic disease with characteristics of rapid onset of seizures, an altered state of consciousness, neurologic decline, and variable degrees of hepatic dysfunction following a respiratory or gastrointestinal infection (e.g. mycoplasma, influenza virus) in a previously healthy child. Brain MRI of patients reveals bilateral, multiple, symmetrical lesions predominantly observed in thalami and brainstem, but also in periventricular white matter and cerebellum in some cases.
A rare genetic, slowly progressive neurodegenerative disease characterised by delayed psychomotor development beginning in infancy, mild to profound intellectual disability, gait and stance ataxia, pyramidal signs (hyperreflexia, extensor plantar responses), dysarthria, and ocular abnormalities (e.g. nystagmus, oculomotor apraxia, abduction deficits, esotropia, ptosis). Brain imaging reveals progressive, generalised cerebellar atrophy, mild ventriculomegaly and in some, retrocerebellar cysts.
A rare genetic neuromuscular disease characterised by congenital hypotonia, generalised, slowly progressive muscular weakness, and proximal joint contractures with distal joint hypermobility and hyperlaxity. Scoliosis or rigidity of the spine and delayed motor milestones are also frequently reported. Other manifestations include a long myopathic face and in rare cases, respiratory failure, mild to moderate intellectual deficiency and short stature. Ambulation may be impaired with time.
A rare genetic, non-dystrophic myopathy with characteristics of fatigable muscle weakness associated with congenital myopathy. Patients present with axial hypotonia, myopathic facies with fatigable ptosis, feeding difficulties, delayed gross motor development and proximal limb weakness with a RYR1-related typical pattern of muscle involvement (i.e. severe involvement of the soleus muscle and sparring of the rectus femoris, sartorius, gracilis and semitendinous muscles). Scoliosis and frequent respiratory tract infections are additional observed features.
A rare congenital arterial duct anomaly with characteristics of saccular dilatation of the ductus arteriosus. It is often asymptomatic or presents shortly after birth with respiratory distress, stridor, cyanosis and/or weak cry. Complications, such as rupture, thromboembolism, infection, airway erosion and/or compression of the adjacent thoracic structures can develop. Spontaneous resolution has been reported.
A very rare developmental defect during embryogenesis with characteristics of varying degrees of congenital fusion (ranging from simple mucosal adhesions to extensive bony fusion) of mandible to maxilla that is not associated with any other malformations. Patients present with mouth opening limitation (which could range from severe to minimal restriction) that typically results in feeding, swallowing and/or respiratory difficulties that may lead to failure to thrive, malnutrition and/or temporomandibular joint ankylosis.
A rare genetic disease caused by lack of lysyl hydroxylase-3 (LH3) activity with characteristics of multiple tissue and organ involvement, including skeletal abnormalities (club foot, progressive scoliosis, osteopenia, pathologic fractures), ocular involvement (flat retinae, myopia, cataracts) and hair, nail and skin anomalies (coarse, abnormally distributed hair, skin blistering, reduced palmar creases, hypoplastic nails). Patients also present intrauterine growth retardation, facial dysmorphism (flat facial profile, low-set ears, shallow orbits, short and upturned nose, downturned corners of mouth) and joint flexion contractures. Growth and developmental delay, bilateral sensorineural deafness, friable diaphragm and later-onset spontaneous vascular ruptures are additional reported features. The disorder is caused by mutation in the PLOD3 gene, which encodes lysyl hydroxylase-3
A rare lethal congenital myopathy syndrome characterised by decreased fetal movements and polyhydramnios in utero and the presence of akinesia, severe hypotonia with respiratory insufficiency, absent reflexes, joint contractures, skeletal abnormalities with thin ribs and bones, intracranial and retinal haemorrhages and decreased birth weight in the neonate.
A rare genetic principally axonal peripheral sensorimotor neuropathy with an X-linked dominant inheritance pattern and the childhood-onset of slowly progressive, moderate to severe, distal muscle weakness and atrophy of the lower extremities, as well as distal, pan modal sensory abnormalities, bilateral foot deformities (pes cavus, clawed toes), absent ankle reflexes and gait abnormalities (steppage gait). Females are usually asymptomatic or only present mild manifestations (mild postural hand tremor, mild wasting of hand intrinsic muscles).
A rare genetic neurodegenerative disease with childhood or adolescent-onset of cerebellar ataxia with dysarthria which slowly progresses and associates pyramidal signs, including lower limb spasticity, brisk reflexes, and Babinski and Hoffman signs. Patients typically present cerebellar ataxia with development of increasing asymmetric spasticity in upper and lower limbs, and variable axonal sensory or sensorimotor neuropathy. Additional heterogeneous features, including pes cavus, scoliosis and abnormalities of the brain (e.g. cerebral atrophy) may also be associated.
A rare genetic epilepsy syndrome characterised by neonatal or early infantile onset of severe, progressive, typically frequent and prolonged myoclonic seizures that are refractory to treatment, associated with localised and/or generalised paroxysmal dystonia (which later becomes persistent). Other features include severe hypotonia, hemiplegia, psychomotor regression (or lack of psychomotor development) and progressive cerebral and cerebellar atrophy, with affected individuals becoming progressively non-reactive to environmental stimuli.
A rare syndromic intellectual disability with primary characteristics of moderate to severe intellectual disability, true-to-relative microcephaly and brain abnormalities including a thin corpus callosum, cerebellar hypoplasia, cerebral white matter hypoplasia and multi-focal hyperintensity of cerebral white matter on MRI. Obesity and distinctive craniofacial dysmorphism (including brachycephaly, round face, straight eyebrows, synophrys, hypertelorism, epicanthus, wide and depressed nasal bridge, protruding ears with uplifted lobe, downslanting corners of the mouth) are additional features.
A rare genetic neurological disease due to SPTBN2 (spectrin beta, non-erythrocytic 2) mutations. The disease has characteristics of global development delay in infancy, followed by childhood-onset gait ataxia with limb dysmetria and dysdiadochokinesia, mild to severe intellectual disability, development of cerebellar atrophy and abnormal eye movements (including a convergent squint, hypometric saccades, jerky pursuit movements and incomplete range of movement). Caused by homozygous mutation in the SPTBN2 gene on chromosome 11q13.
A rare genetic neurological disorder defined by early-onset of neurologic symptoms, biphasic clinical course, unique MRI features (including extensive, symmetrical, deep white matter abnormalities), and increased lactate in body fluids. The severe form has characteristics of delayed psychomotor development, seizures, early-onset hypotonia and persistently increased lactate levels. The mild form usually presents with irritability, psychomotor regression after six months of age and temporary high lactate levels, with overall clinical improvement from the second year onward. The disease is caused by homozygous or compound heterozygous mutation in the EARS2 gene on chromosome 16p.
A form of hereditary spastic paraplegia with usual characteristics of a pure phenotype of a slowly progressive spastic paraplegia associated with urinary incontinence with an onset in mid to late-adulthood. A complex phenotype, with the additional findings of cognitive impairment, sensorimotor polyneuropathy, ataxia and Parkinsonism as well as thin corpus callosum and white matter lesions (seen on magnetic resonance imaging) has also been reported.
A rare genetic skin pigmentation anomaly disorder with characteristics of progressive, diffuse, partly blotchy, hyperpigmented lesions that are intermixed with multiple cafe au lait spots, hypopigmented maculae and lentigines and are located on the face, neck, trunk and limbs, as well as, frequently, the palms, soles and oral mucosa. Dyspigmentation pattern can range from well isolated cafe au lait/hypopigmented patches on a background of normal-appearing skin to confetti-like or mottled appearance. There is evidence this disease is caused by heterozygous mutation in the KIT ligand gene (KITLG) on chromosome 12q22.
A pure form of hereditary spastic paraplegia with a childhood to adulthood-onset of slowly progressive spastic gait, extensor plantar responses, brisk tendon reflexes in arms and legs, decreased vibration sense at ankles and urinary dysfunction. Ankle clonus is also reported in some patients.
A pure form of hereditary spastic paraplegia with late childhood to early adulthood-onset of slowly progressive spastic paraplegia with spastic gait and lower limb hyperreflexia, brisk tendon reflexes and ankle clonus. Lower limb pain and reduced lower limb vibratory sense is also reported in some older adult patients.
A form of hereditary spastic paraplegia characterised by either a pure phenotype of slowly progressive spastic paraplegia of the lower extremities with bladder dysfunction and pes cavus or a complex presentation with additional manifestations including cerebellar signs, nystagmus, distal or generalised muscle atrophy and cognitive impairment. Age of onset is highly variable, ranging from early childhood to adulthood. White matter hyperintensity and cerebellar and spinal cord atrophy may be noted on brain magnetic resonance imaging in some patients. The disease is caused by homozygous or compound heterozygous mutation in the CYP7B1 gene on chromosome 8q12.
A pure form of hereditary spastic paraplegia with a childhood to adulthood-onset of slowly progressive lower limb spasticity and hyperreflexia of lower extremities, extensor plantar reflexes, distal sensory impairment, variable urinary dysfunction and pes cavus. The disease is caused by heterozygous mutation in the RTN2 gene on chromosome 19q13.
A pure form of hereditary spastic paraplegia with characteristics of a slowly progressive and relatively benign spastic paraplegia presenting in adulthood with spastic gait, lower limb hyperreflexia, extensor plantar responses, bladder dysfunction (urinary urgency and/or incontinence), and mild sensory and motor peripheral neuropathy.
A pure form of hereditary spastic paraplegia with a childhood or adolescent onset of slowly progressive, pure crural muscle spastic paraparesis which manifests with mild lower limb weakness, gait difficulties, extensor plantar responses, and hyperreflexia of lower extremities. Less common manifestations reported include cerebellar oculomotor disturbance with saccadic eye pursuit, pes cavus and scoliosis. Some patients also present pin and vibration sensory loss in distal legs. The disease is caused by homozygous or compound heterozygous mutation in the DDHD1 gene on chromosome 14q22.
A form of hereditary spastic paraplegia presenting with either a pure spastic paraplegia phenotype, usually in the first or second decade of life, with spastic lower extremities, unsteady spastic gait, hyperreflexia and extensor plantar responses, or as a complicated phenotype with the additional manifestations of distal wasting, saccadic ocular movements, mild cerebellar ataxia and mild, distal, axonal neuropathy.
A complex form of hereditary spastic paraplegia with characteristics of spastic paraplegia, demyelinating peripheral sensorimotor neuropathy, poikiloderma (manifesting with loss of eyebrows and eyelashes in childhood in addition to delicate, smooth, and wasted skin) and distal amyotrophy (presenting after puberty). There have been no further descriptions in the literature since 1992.
A rare chromosomal anomaly syndrome resulting from the partial deletion of chromosome 16, with characteristics of pre and postnatal growth delay, severe developmental delay, intellectual disability, speech delay, and craniofacial dysmorphism (e.g. microcephaly, hypertelorism, downslanted palpebral fissures, ptosis, telecanthus, low set and dysmorphic ears, broad flat nasal bridge, down-turned mouth corners, high palate, retrognathia). Patients may also present congenital cataract, mild synophrys, hypotonia, and poor social contact. Congenital heart anomalies (e.g. ventricular septal defect, patent ductus arteriosus) have also been reported.
A rare chromosome Y structural anomaly, with a highly variable phenotype, mostly characterised by short stature, partial to total gonadal failure, sexual infantilism, genital anomalies (e.g. ambiguous genitalia, hypospadias, cryptorchidism), and azoospermia or oligozoospermia. Additional reported features include speech delay, obesity, and acanthosis nigricans. Gender dysphoria and comorbid bipolar disorder have also been observed.
An extremely rare highly malignant soft tissue sarcoma located in the uterine body and arising from primitive mesenchymal cells displaying variable degrees of skeletal muscle differentiation. It most often presents with abnormal vaginal discharge or dysfunctional uterine bleeding, abdominal pain and lower abdominal mass. Association with DICER1 syndrome has been reported.
A rare genetic, peripheral sensorimotor neuropathy with an X-linked dominant inheritance pattern and the childhood-onset (within the first decade in males) of progressive, distal, moderate to severe muscle weakness and atrophy in lower extremities and intrinsic hand muscles, pes cavus, bilateral foot drop, reduced or absent tendon reflexes, as well as mild to moderate sensory impairment in lower extremities. Females tend to have milder manifestations or may be asymptomatic. Sensorineural deafness and central nervous system involvement have also been reported. The disease is caused by hemizygous or heterozygous mutation in the GJB1 gene on chromosome Xq13.
A rare genetic peripheral sensorimotor neuropathy with an X-linked recessive inheritance pattern and the infantile to childhood-onset of progressive, distal muscle weakness and atrophy (more prominent in the lower extremities than in the upper extremities), pes cavus, and absent tendon reflexes. Sensory impairment and intellectual disability has been reported in some individuals.
A rare genetic peripheral sensorimotor neuropathy with an X-linked recessive inheritance pattern and the childhood to adolescent-onset of progressive, distal muscle weakness and atrophy (beginning in the lower extremities and then affecting the upper extremities), as well as distal, pan sensory loss in the upper and lower extremities, pes cavus, and absent or reduced distal tendon reflexes. Pain and paresthesia are frequently the initial sensory symptoms. Spastic paraparesis (manifested by clasp-knife sign, hyperactive deep-tendon reflexes, and Babinski sign) has also been reported.
A rare genetic peripheral sensorimotor neuropathy with an X-linked recessive inheritance pattern and the infancy to childhood-onset of progressive distal muscle weakness and atrophy (first appearing and more prominent in the lower extremities than the upper) which usually manifests with foot drop and gait disturbance, bilateral profound prelingual sensorineural hearing loss and progressive optic neuropathy. Females are asymptomatic and do not display the phenotype.
A rare genetic developmental defect during embryogenesis. The disease has the typical lethal multiple pterygium syndrome presentation comprising of multiple pterygia, severe arthrogryposis, cleft palate, cystic hygromata and/or fetal hydrops, skeletal abnormalities and fetal death in the second or third trimester with an X-linked pattern of inheritance.
An extremely rare clonal lymphoid proliferation of the ocular surface with an indolent course. Clinically it presents with treatment-resistant conjunctivitis, ptosis, and excessive tear production or as a painless, salmon-pink, ''fleshy'' patch, with a smooth or multinodular surface, on the bulbar conjunctiva. Histologically it is usually B-cell Non-Hodgkin lymphoma (most often extranodal marginal zone B-cell lymphoma, followed by follicular and diffuse large B-cell lymphoma), with conjunctival T-cell Non-Hodgkin lymphoma being very rare.
A rare chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 13. The syndrome has a highly variable phenotype and typical characteristics of varying degrees of intellectual disability and developmental delay, as well as central nervous system malformations (e.g. holoprosencephaly, anencephaly, ventriculomegaly, Dandy-Walker malformation), ocular abnormalities (e.g. hypertelorism, microphthalmia, strabismus, aniridia, retinal dysplasia) and craniofacial dysmorphism (microcephaly, trigonocephaly, large and malformed ears, broad prominent nasal bridge, micrognathia). Cardiac, genitourinary, gastrointestinal and skeletal manifestations have also been reported.
A rare chromosomal anomaly syndrome resulting from a partial deletion of the short arm of chromosome 3. The syndrome has a highly variable phenotype with typical characteristics of pre and post-natal growth retardation, intellectual disability, developmental delay and craniofacial dysmorphism (microcephaly, trigonocephaly, downslanting palpebral fissures, telecanthus, ptosis, micrognathia). Postaxial polydactyly, hypotonia, renal anomalies and congenital heart defects (e.g. atrioventricular septal defect) may be associated.
A rare chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 7. The syndrome has a highly variable phenotype with typical characteristics of holoprosencephaly, growth restriction, developmental delay, facial dysmorphism (facial clefts, prominent forehead, hypertelorism, low-set ears, flat and broad nasal bridge, large mouth), abnormal fingers and palm or sole creases, ocular abnormalities, and other congenital malformations (including genital anomalies and caudal deficiency sequence). Cardiopathies have been occasionally reported.
A rare genetic otorhinolaryngologic disease characterised by respiratory morbidity due to lack of cilia on the respiratory tract epithelial cells. The disease manifests from birth with respiratory distress, neonatal pneumonia, dyspnoea, lobar atelectasis and bronchiectasis. Recurrent infections of the upper and lower respiratory tract, chronic humid coughing, and chronic sinusitis, otitis and rhinitis are typical lifelong presenting conditions.
A rare neurologic disease characterised by the onset of generalised or focal seizures following immersion of the head in hot water, or with hot water being poured over the head. Primary generalised tonic-clonic seizures have been reported in rare cases.
A congenital non-syndromic limb malformation with the presence of an accessory phalanx between metacarpal/metatarsal and proximal phalanx, or between any two other phalanges of a digit, excluding the thumb. Hyperphalangy is almost always bilateral and patients present no more than five digits and no other skeletal anomalies.
A developmental anomaly with characteristics as birth of right-sided aortic arch, craniofacial dysmorphism (microcephaly, asymmetric, facial bones, broad forehead, borderline hypertelorism, nasal septum deviation, large nasal cavity, large, posteriorly rotated ears and microstomia with downturned corners), and intellectual disability. These features were observed in 4 members of one family, involving 2 successive generations, suggesting an autosomal dominant mode of transmission. There have been no further descriptions in the literature since 1968.
A rare benign congenital malformation of the lymphatic system with a polypoidal, variable-sized, soft tissue mass located in the larynx. Most lesions manifest by the second year of life and depending on the size, patients may present with changes in voice, dysphagia, stridor, airway obstruction and/or respiratory distress. Cystic hygroma of the neck is frequently associated.
A rare acquired eye disease due to long-term exposure to chloroquine or hydroxychloroquine with slowly progressive, usually non-reversible, development of bilateral atrophic bull's-eye maculopathy (progressive loss of central vision acuity, reduced color vision and central scotoma), which in severe cases can spread over the entire fundus, leading to widespread retinal atrophy and visual loss.
A rare neurologic disease characterised by seizures induced by specific cognitive tasks, such as calculation or solving arithmetic problems, playing thinking games (e.g. chess, cards), thinking, making decisions and abstract reasoning. Idiopathic generalised seizures are mainly involved, but partial epilepsies may, in rare cases, be observed.
A rare primary immunodeficiency disorder due to impaired capacity of activated T and B-cells to proliferate in response to antigen receptor-mediated activation. The disease has characteristics of early-onset severe persistent and/or recurrent viral infections due to Epstein-Barr virus and Varicella Zoster virus as well as recurrent sino-pulmonary bacterial infections due to encapsulated pathogens.
A rare genetic non-syndromic congenital limb malformation with characteristics of unilateral fusion of second to fifth fingers, amalgamation of distal phalanges in a knot-like structure, and second and third-toe fusion. Some individuals present only with webbing between second and third toes without involvement of fingers.
A rare neurologic disease with characteristics of frequent and spontaneous epileptic seizures (frequently with symmetrical or asymmetrical tonic features) triggered by a normal startle in response to a sudden and unexpected somatosensory (most frequently auditory) stimulus. Falls are common and can be traumatic. In most cases, the disease is associated with spastic hemiplegia, spastic diplegia or spastic tetraplegia and intellectual disability.
A rare genetic disorder of sex development with either the coexistence of both male and female reproductive gonads or, more frequently, the presence of one or both gonads containing a mixture of both testicular and ovarian tissue (ovotestes) in an individual with a normal male 46, XY karyotype. External genitalia are usually ambiguous, but can range from normal male to normal female and if a uterus and/or fallopian tubes are present, they are generally hypoplastic. Cryptorchidism, hypospadias, infertility and increased risk of gonadal neoplasm are frequently associated.
A rare bone development disorder with characteristics of intellectual disability, short stature, turribrachycephaly, facial dysmorphism (severe hypertelorism, hypoplasia of supraorbital ridges, abnormal ears, and micrognathia), bony defects of the occiput, and digital anomalies (including syndactyly, oligodactyly, and/or brachydactyly). Urethral atresia has also been reported. There have been no further descriptions in the literature since 1987.
A rare mitochondrial disease with marked clinical variability typically and characteristics of encephalomyopathy, kidney disease (nephrotic syndrome), optic atrophy, early-onset deafness, pancytopenia, obesity, and cardiac disease (valvulopathy). Additionally, macrocephaly, intellectual disability, elevated lactate/pyruvate ratio, insulin-dependent diabetes, livedo reticularis, liver dysfunction and seizures have also been associated.
A rare genetic non-syndromic congenital limb malformation with characteristics of angulation of a digit in the radio-ulnar (coronal) plane, away from the axis of joint flexion-extension, in several members of a single family with no other associated manifestations. Deviation is usually bilateral and commonly involves the fifth finger. Affected digits present trapezoidal or delta-shaped phalanges on imaging.
A rare primary immunodeficiency disorder with characteristics of persistent CD4 T-cell lymphopenia (less than 300 cells/UL on multiple occasions) not associated with any other underlying primary or secondary immune deficiency. Patients typically present opportunistic infections (with cryptococcal, mycobacterial, candidal, varicella zoster virus infections and progressive multifocal leukoencephalopathy being the most prevalent), malignancies (mainly lymphoproliferative disorders), or autoimmune disorders. Some individuals are asymptomatic and incidentally diagnosed.
A rare genetic endocrine disorder characterised by persistently high prolactin serum levels (not associated with gestation, puerperium, drug intake or pituitary tumour) in multiple affected family members. Clinically it manifests with signs usually observed in hyperprolactinaemia, which are: secondary medroxyprogesterone acetate (MPA)-negative amenorrhoea and galactorrhoea in female patients, and hypogonadism and decreased testosterone level-driven sexual disfunction in male patients. Oligomenorrhoea and primary infertility have also been reported in some female patients.
A rare non-syndromic urogenital tract malformation with the familial occurrence of retrograde flow of urine from the bladder into the ureter and sometimes the kidneys. Patients may be asymptomatic or may present with recurrent, sometimes febrile, urinary tract infections that, in case of acute pyelonephritis, may lead to serious complications (renal scarring, hypertension, renal failure). Spontaneous resolution of the disorder is possible.
A rare non-syndromic central nervous system malformation disorder with characteristics of severe microcephaly, overlapping sutures, keel-like occipital bone prominence, scalp rugae with normal hair pattern and signs of neurological impairment. Brain imaging may show ventriculomegaly, cortical tissue deficit, and hydranencephaly.
A rare genetic distal myopathy with characteristics of slowly progressive distal to proximal limb muscle weakness and atrophy and early involvement of thenar and hypothenar muscles. Patients present with clumsiness of the hands and stumbling in the fourth to fifth decade of life, and later develop steppage gait and contractures of the hands. Progressive fatty degeneration affects intrinsic muscles of the hands, gluteus medium and both anterior and posterior compartment muscles of the distal lower extremities, with later involvement of forearm muscles, triceps, infraspinatus and the proximal lower limb muscles. Asymmetry of muscle involvement is common.
A rare inborn error of metabolism characterised by persistent hypermethioninaemia with increased levels of S-adenosylmethionine and S-adenosylhomocysteine which manifests with encephalopathy, severe global developmental delay, mild to severe liver dysfunction, hypotonia and facial dysmorphism (most significant is frontal bossing, macrocephaly, hypertelorism and depressed nasal bridge). Epileptic seizures, hypoglycaemia and/or cardiac defects (pulmonary stenosis, atrial and/or ventricular septal defect, coarctation of the aorta) may be associated. Clinical picture may range from neurological symptoms only to multi-organ involvement. There is evidence the disease is caused by homozygous mutation in the ADK gene on chromosome 10q22.
A rare genetic neurodegenerative disorder with characteristics of severe, persistent hypotonia (presenting at birth or in early infancy), severe global developmental delay (with poor or absent speech, difficulty or inability to roll, sit or walk), profound intellectual disability and failure to thrive. Additional manifestations include microcephaly, progressive peripheral spasticity, bilateral strabismus and nystagmus, constipation and variable dysmorphic facial features (including plagiocephaly, broad forehead, small nose, low-set ears, micrognathia and open mouth with tented upper lip).
A rare neurologic disease with characteristics of unpredictable, transient and spontaneous unresponsiveness lasting from hours to days, with a frequency of three to seven attacks per year, in the absence of readily discernible toxic, metabolic or structural causes.
A rare genetic intellectual disability syndrome with characteristics of delayed motor and cognitive development, absence or severe delay in speech development, intellectual disability and alacrima. Achalasia/dysphagia and mild autonomic dysfunction (anisocoria) have also been reported in some patients. The phenotype is similar to the one observed in autosomal recessive Triple A syndrome, but differs by the presence of intellectual disability in all affected individuals.
A rare developmental defect during embryogenesis with characteristics of mild to moderate intellectual disability and psychomotor delay, Robin sequence (including severe micrognathia and soft palate cleft) and distinct dysmorphic facial features (e.g. synophrys, short palpebral fissures, hypertelorism, small, low-set and posteriorly angulated ears, bulbous nose, long/flat philtrum and bow-shaped upper lip). Skeletal anomalies such as brachydactyly, clinodactyly, small hands and feet, and oral manifestations (e.g. bifid, short tongue, oligodontia) are also associated. Additional features reported include microcephaly, capillary hemangiomas on face and scalp, ventricular septal defect, corneal clouding, nystagmus and profound sensorineural deafness.
A rare non-syndromic congenital heart malformation characterised by the presence of a congenital aneurysm of the membranous portion of the interventricular septum. Patients may be asymptomatic or may present with ventricular or supraventricular tachycardia, fatigue, exertional dyspnoea, palpitations, and cardiac murmur. Ventricular septal defects and conduction defects, such as first-degree atrio-ventricular block or incomplete right bundle branch block, may also be also associated.
A rare genetic developmental defect during embryogenesis disorder with characteristics of the lack of epidermal ridges on the palms and soles, resulting in the absence of fingerprints, with no other associated manifestations. It is associated with a reduced number of sweat gland openings and reduced transpiration of palms and soles. There is evidence the disorder is caused by heterozygous mutation in the SMARCAD1 gene on chromosome 4q22.
A rare multiple congenital anomalies syndrome with manifestations of bilateral congenital dislocation of the hip, characteristic facial features (flat mid-face, hypertelorism, epicanthus, puffiness around the eyes, broad nasal bridge, carp-shaped mouth), and joint hyperextensibility. Congenital heart defects, congenital dislocation of the knee, congenital inguinal hernia, and vesicoureteric reflux have also been reported. There have been no further descriptions in the literature since 1995.
A rare bacterial infectious disease caused by extraintestinal infection of non-typhoidal serotypes of Salmonella enterica in patients with underlying HIV infection, malaria or malignancy. It has a high mortality rate and patients typically present with fever, pallor and respiratory signs (cough, tachypnea, pneumonia). Gastrointestinal manifestations (diarrhea, vomiting, abdominal pain) are not common. Occasionally, organ abscesses, septic shock and meningitis may be observed.
A rare intellectual disability syndrome characterised by macrocephaly, mild dysmorphic features (frontal bossing, long face, hooded eye lids with small, downslanting palpebral fissures, broad nasal bridge, and prominent chin), global neurodevelopmental delay, behavioural abnormalities (e.g. anxiety, stereotyped movements) and absence or generalised tonic-clonic seizures. Additional features reported in some patients include craniosynostosis, fifth finger clinodactyly, recurrent pneumonia, and hepatosplenomegaly. The disease is caused by homozygous or compound heterozygous mutation in the KPTN gene on chromosome 19q13.
A rare genetic distal myopathy with characteristics of slowly progressive distal limb muscle weakness and atrophy (beginning with anterior tibial muscle involvement followed by the intrinsic hand muscles) in association with reduced sensation in a stocking-glove distribution. Patients present with high stepping gait, ankle areflexia and contractures in the first to second decade of life, associated with marked ankle extensor muscle atrophy; later proximal muscle involvement is moderate and ambulation is preserved throughout the life.
A rare genetic primary bone dysplasia with characteristics of laxity, dislocations and contractures of the joints, short stature, foot deformities (e.g. clubfeet), broad tips of fingers and toes, short neck, dysmorphic facial features (hypertelorism, downslanting palpebral fissures, upturned nose with anteverted nares, high arched palate) and various cardiac malformations. Severe disease is associated with multiple fractures, osteopenia, arachnodactyly and blue sclerae. A broad spectrum of additional features, including scoliosis, radio-ulnar synostosis, mild developmental delay and various eye disorders (glaucoma, amblyopia, hyperopia, astigmatism, ptosis), are also reported.
A rare neuroimmunological disorder with the onset of cognitive deficits, psychiatric disturbances (e.g. personality changes), seizures, peripheral nerve hyperexcitability, dysautonomia, neuropathic pain, insomnia and weight loss, in association with detection of caspr2 antibodies in serum or cerebrospinal fluid, with or without underlying malignancies. Other features reported include blepharoclonus, myoclonic status epilepticus, and dyskinesia.
A rare neuroimmunological disorder characterised by the onset of cognitive decline, psychiatric disturbances and seizures (distinctively faciobrachial dystonic seizures) in association with detection of LGI1 antibodies in serum or cerebrospinal fluid. Patients may present with confusion, hallucinations, vocalisation, paranoia, tangentiality, aggressive outbursts and/or spatial disorientation, as well as obstinate hyponatraemia. It is most often non-paraneoplastic, however comorbid tumours, such as small cell lung cancer and thymoma, have been reported.
A rare subtype of acute myeloid leukaemia with recurrent cytogenetic abnormalities characterised by clonal proliferation of myeloid blasts with predominantly megakaryoblastic differentiation in the bone marrow and blood, often with extensive infiltration of the abdominal organs. It occurs typically in infants and usually presents with hepatosplenomegaly, anaemia, thrombocytopenia and nonspecific symptoms related to ineffective haematopoesis (fatigue, bleeding and bruising, recurrent infections). Myelofibrosis and fibrosis of other infiltrated organs is also characteristic of this disease.
An extremely rare subtype of hereditary motor and sensory neuropathy with characteristics of severe, rapidly progressing, distal, symmetric polyneuropathy and microcephaly (which can be evident in utero) with intact cognition. Clinically it presents with delayed motor development, hypotonia, absent or reduced deep tendon reflexes, progressive muscle wasting and weakness and scoliosis.
A rare neurologic disease with characteristics of tonic posturing or clonic movements triggered by micturition. Involvement of the extremities may be unilateral or bilateral. This may occur with or without loss of consciousness. Developmental delay is reported in some cases.
A rare genetic developmental defect during embryogenesis with characteristics of various ophthalmic anomalies (including congenital microphthalmia, microcornea, cataract, anterior segment dysgenesis, ocular coloboma and early onset rod-cone dystrophy) and abnormal external ears (low-set pinna with crumpled helix, narrow intertragic incisure, abnormal bridge connecting the crus of the helix and the anthelix, narrow external acoustic meatus and lobule aplasia). There is evidence the disease is caused by homozygous mutation in the HMX1 gene on chromosome 4p16.
A rare neurologic disease characterised by complex partial seizures with or without secondary generalisation, or idiopathic primarily generalised epilepsy, triggered by sexual orgasm. Seizures usually start immediately, shortly after or a few hours after the achievement of orgasm, last a few seconds or minutes, and are followed, in very rare cases, by intense migraine.
A rare genetic ectodermal dysplasia syndrome with characteristics of almost total alopecia with only sparse, thin, brittle, slow-growing scalp hair, fair and sparse eyebrows and eyelashes, absent axillary and pubic hair, fragile and brittle fingernails, thick and brittle toenails (both with a subungual corneal layer), hypodontia, microdontia, widely spaced teeth with hypoplastic enamel, mild palmoplantar keratosis, cafe au lait spots and areolae anomalies. There have been no further descriptions in the literature since 1985.
A rare subtype of orofaciodigital syndrome with sporadic occurrence and characteristics of cardiac (septum hypertrophy) and central nervous system abnormalities (myelomeningocele, Sylvius aqueduct stenosis, corpus callosum agenesis, vermis hypoplasia), in addition to oral, facial and digital malformations (gingival frenulum, bifid tongue, supernumerary teeth, macrocephaly, hypertelorism, pre- and post-axial polydactyly in hands, preaxial polydactyly in feet and club feet). Skeletal anomalies, such as short tibiae and central, Y-shaped metacarpals are also associated.
A rare subtype of orofaciodigital syndrome, with sporadic occurrence and characteristics of cardiac (mitral and tricuspid valve dysplasia) and neuropsychiatric manifestations (epilepsy, depression), in addition to oral, facial and digital malformations (lingual hamartomas, cleft lip, and brachydactyly, clinodactyly, syndactyly of hands and feet). Leukoaraiosis on brain MRI examination is also associated.
A rare subtype of orofaciodigital syndrome, with autosomal recessive inheritance and C2CD3 mutations. The disease has characteristics of severe microcephaly, trigonocephaly, severe intellectual disability and micropenis, in addition to oral, facial and digital malformations (gingival frenulum, lingual hamartomas, cleft/lobulated tongue, cleft palate, telecanthus, up-slanting palpebral fissures, microretrognathia, postaxial polydactyly of hands and duplication of hallux). Corpus callosum agenesis and vermis hypoplasia with molar tooth sign on brain imaging are also associated.
A rare genetic developmental defect during embryogenesis with primary characteristics of congenital hypopituitarism and/or postaxial polydactyly. It can be associated with short stature, delayed bone age, hypogonadotropic hypogonadism, and/or midline facial defects (e.g. hypotelorism, mild midface hypoplasia, flat nasal bridge, and cleft lip and/or palate). Hypoplastic anterior pituitary and ectopic posterior pituitary lobe are frequent findings on MRI examination.
A rare genetic, poly malformative syndrome with characteristics of progressive, proportionate, asymmetric segmental overgrowth (with soft tissue hypertrophy and ballooning effect) that develops and progresses rapidly in early childhood, arteriovenous and lymphatic vascular malformations, lipomatosis and linear epidermal nevus (arranged in whorls along the lines of Blaschko). Clinical symptoms of Cowden syndrome, such as macrocephaly and progressive development of numerous hypertrophic hamartomatous and neoplastic lesions involving multiple organs and systems are also associated. Patients present an increased risk of developing cancer.
A primary bone dysplasia with characteristics of height that is 2 standard deviations below the corresponding mean height for a given age, sex and population group, in the absence of obvious skeletal abnormalities and other diseases and with normal developmental milestones. Patients present normal bone age with normal limbs, shortening of the extremities (significantly lower extremities-trunk and sitting height-to-height ratios), normal hGH values, normal karyotype, and Leri-Weill dyschondrosteosis-like radiological signs. Mesomelic disproportions and Madelung deformity are not apparent at a young age but may develop later in life or never.
A rare neurological disease characterised by the development of paraesthesia as well as in severe cases progressive paresis and paralysis following irradiation of tumours in which the spinal cord is included within the radiation field. Symptoms may develop months or years after radiation therapy was administered.
A rare genetic primary bone dysplasia with highly variable phenotype typically characterised by platyspondyly, brachydactyly type E changes (short metacarpals and metatarsals, short distal phalanges in hands and feet), bilateral short ulnae and mild short stature. Other reported features include additional skeletal findings (e.g. midface hypoplasia, degenerative changes in proximal femora, limited elbow extension, bilateral sacralisation of L5, clubfeet), as well as myopia, hearing loss, and intellectual disability.
A rare bacterial pulmonary infectious disease caused by a Panton-Valentine leukocidin-producing Staphylococcus aureus strain, characterised by severe respiratory failure, extensive, rapidly progressing pneumonia and haemorrhagic lung necrosis. Patients typically present with influenza-like symptoms, such as fever, cough, and chest pain, as well as haemoptysis, hypotension, leukopenia, and severe respiratory symptoms that rapidly evolve to acute respiratory distress syndrome and septic shock. High mortality is associated.
A rare developmental defect during embryogenesis with the specific association of glandular hypospadias and lumbo-sacral spina bifida. Affected individuals may or may not present additional congenital anomalies, such as hydrocephaly, microstomia, patent ductus arteriosus, cryptorchidism, intestinal malrotation, rocker-bottom feet and hypertrichosis.
A rare genetic congenital hypothyroidism disorder with characteristics of mild global developmental delay in childhood, short stature, delayed bone age and abnormal thyroid and selenium levels in serum (high total and free T4 concentrations, low T3, high reverse T3, normal to high TSH, decreased selenium). Intellectual disability, primary infertility, hypotonia, muscle weakness and impaired hearing have also been reported. The disease can be caused by homozygous or compound heterozygous mutation in the SECISBP2 gene on chromosome 9q22.
Syndrome with characteristics of ataxia, delayed dentition, hypomyelination and cerebral atrophy. So far eight cases have been described. There is evidence that the disease is caused by homozygous or compound heterozygous mutation in the POLR3A gene on chromosome 10q22.
A rare genetic male infertility due to sperm disorder with characteristics of the presence of spermatozoa with abnormal morphology, such as macrozoospermia or globozoospermia, in over 85% of sperm, resulting from mutation in a single gene known to cause teratozoospermia. It is a heterogeneous group that includes a wide range of abnormal sperm phenotypes affecting, solely or simultaneously, head, neck, midpiece and/or tail.
A rare genetically highly heterogeneous otorhinolaryngologic disease, resulting from inner and/or middle ear or hearing nerve anomalies, with typical characteristics of progressive, bilateral, moderate to profound hearing loss (mean sensorineural hearing impairment equal to 40 dB or more for 500-1,000-and 2,000-Hz frequency tones in the better ear) which occurs after the onset of speech development and is not associated with visible external ear abnormalities or any other medical problems. Language development is not initially significantly delayed.
A rare genetically highly heterogeneous otorhinolaryngologic disease, resulting from inner and/or middle ear or hearing nerve anomalies, with typical characteristics of bilateral, severe to profound hearing loss (mean sensorineural hearing impairment of 60 dB or more for 500-1,000-, and 2,000-Hz frequency tones in the better ear) which occurs before the onset of speech development and is not associated with visible external ear abnormalities or any other medical problems. It is usually nonprogressive and impedes oral language acquisition.
A rare flea-borne Rickettsial disease caused by a Rickettsia felis infection. Patients can be asymptomatic or can present with unspecific symptoms such as fever, headache, generalised maculopapular rash, myalgia, arthralgia and, occasionally eschar, lymphadenopathy, nausea, vomiting, loss of appetite and abdominal pain. Rarely, serious manifestations may occur and include neurological dysfunction (photophobia, hearing loss and signs of meningitis) and pulmonary compromise.
A very rare hereditary epidermal disorder characterised by hypotrichosis/woolly scalp hair, sparse body hair, eyelashes and eyebrows, leukonychia and striate palmoplantar keratoderma (more severe on the soles than the palms), which progressively worsens with age. Pseudo ainhum of the fifth toes was also reported. Although the syndrome shares clinical similarities with both Naxos disease and Carvajal syndrome, cardiomyopathy is notably absent. There is evidence the disease is caused by homozygous mutation in the KANK2 gene on chromosome 19p13
Inherited disorder characterised by episodes of metabolic crisis and acute encephalopathy. Life-threatening episodes manifest with poor feeding, vomiting, weight loss, lethargy, tachypnea, seizures or coma and are caused by hyperammonaemia, metabolic acidosis, respiratory alkalosis, hypoglycaemia and reduced production of bicarbonate in the liver. Caused by mutations in the CA5A gene resulting in absent or impaired carbonic anhydrase VA enzyme function leading to reduced bicarbonate production. Inherited in an autosomal recessive pattern.
A rare chromosomal anomaly syndrome with a highly variable phenotype. Principle characteristics are developmental or growth delay, short stature, craniofacial dysmorphism (turricephaly, tall forehead, downslanting palpebral fissures, posteriorly rotated and low set ears, narrow palate), congenital heart defects (atrial septal defect, patent ductus arteriosus), hypotonia, and pigmentary dysplasia. Scoliosis, hearing loss, facial/body asymmetry and intellectual disability have also been reported.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 13 with variable phenotype. Principle characteristics are intellectual disability, psychomotor delay, craniofacial dysmorphism (microcephaly, bushy eyebrows, long curled eyelashes, hypotelorism, low-set ears, prominent nasal bridge, long philtrum, high palate, thin upper lip), short neck, polydactyly, and haemangiomas. Cardiac, urogenital and neural tube defects, as well as umbilical and inguinal hernias, seizures and hypotonia, have also been reported.
A rare chromosomal anomaly syndrome resulting from the partial trisomy of the long arm of chromosome 16 with variable phenotype. Principle characteristics are developmental delay, severe intellectual disability, hypotonia, facial dysmorphism (high, prominent forehead, epicanthic folds, dysplastic ears, broad/depressed nasal bridge, malar hypoplasia, narrow and arched palate, thin upper lip vermilion, micrognathia) and hand/feet anomalies (arachnodactyly, talipes equinovarus). Cardiac defects, genitourinary malformations and vertebral anomalies are also associated. Thrombocytopenia and recurrent infections have also been reported.
A rare chromosomal anomaly syndrome resulting from partial trisomy of the long arm of chromosome 20 with high phenotypic variability. The disease has characteristics of neurodevelopmental delay, cardiac malformations (ventricular septal defect, coarctation of aorta) and facial dysmorphism (large/high forehead, microphthalmia, upslanting palpebral fissures, epicanthus, large, long, low-set ears, anteverted nares, protruding upper lip, cleft lip/palate, micro/retrognathia, dimpled chin). Skeletal (brachydactyly, scoliosis, pectus excavatum) and cerebral anomalies have also been reported.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 22 with variable phenotype. Principle characteristics are varying degrees of intellectual disability and developmental delay, pre and postnatal growth deficiency, hypotonia, and craniofacial dysmorphism (microcephaly, hypertelorism, narrow and upslanted palpebral fissures, epicanthic folds, low-set dysplastic ears, broad and depressed nasal bridge, cleft lip an/or palate, long philtrum, retro/micrognathia). Congenital heart defects, as well as cerebral, skeletal, renal and genital anomalies have also been reported.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the short arm of chromosome 2 with a highly variable phenotype. Principle characteristics are pre and post-natal growth failure, global developmental delay, facial dysmorphism (high forehead/frontal bossing, abnormal ear shape and/or position, hypertelorism/telecanthus, broad/depressed nasal bridge) and ocular anomalies (exophthalmos, retinal hypopigmentation, optic nerve and foveal hypoplasia). Other reported anomalies include hypotonia, pectus excavatum, long fingers and toes, syndactyly, congenital heart (ventricular, atrial septal defects) and neural tube defects, seizures, pulmonary hypoplasia, diaphragmatic hernia and urogenital anomalies.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the short arm of chromosome 3 with highly variable phenotype. Principle characteristics are craniofacial dysmorphism (brachy/microcephaly, square facies, frontal bossing, bitemporal indentation, hypertelorism/telecanthus, low-set and/or dysmorphic ears, short nose with broad, flat nasal bridge, prominent cheeks and philtrum, downturned corners of mouth, micrognathia/retrognathia, short neck) associated with psychomotor delay, moderate to severe intellectual disability, cardiac (patent ductus arteriosus) and urogenital (renal hypoplasia, hypogenitalism) abnormalities, as well as seizures and presence of whorls on fingers.
A rare chromosomal anomaly resulting from the partial trisomy of the long arm of chromosome 9 with a variable phenotype. The disease has characteristics of psychomotor and speech delay, intellectual disability, hypotonia, long narrow habitus, craniofacial dysmorphism (micro/dolichocephaly, facial asymmetry, narrow palpebral fissures, deep-set eyes, strabismus, microphthalmia, abnormally shaped ears, microstomia, micro/retrognathia) and hand and feet anomalies (arachnodactyly, camptodactyly, abnormal implantation of digits). Congenital flexion contractures and limited joint movements have also been observed.
A very rare congenital anomaly of the great arteries characterised by the presence of two aortic arches (right and left) which encircle and compress the trachea and oesophagus, resulting in various respiratory and gastrointestinal symptoms (e.g. harsh breathing, stridor, dyspnoea, cyanotic and choking episodes, chronic cough, recurrent respiratory tract infections, dysphagia and reflux). Oesophageal atresia and tracheooesophageal fistula have also been reported. It usually occurs isolated, but, on occasion, may be associated with other congenital heart anomalies and chromosomal aberrations.
A rare genetic hair anomaly with characteristics of a prolonged anagen phase of the eyelash hairs, leading to extreme eyelash growth that may result in corneal irritation. Increased growth of hair on other parts of the face (eyebrows, cheeks, forehead) and/or the body (chest, arms, legs) may be associated. There is evidence the disease is caused by homozygous mutation in the FGF5 gene on chromosome 4q21.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 22 with a highly variable phenotype. Principle characteristics are developmental delay, intellectual disability, hypotonia, growth retardation, velopharyngeal insufficiency, mild craniofacial dysmorphism (microcephaly, tall/broad forehead, small downslanting palpebral fissures, hooded eyelids, flat nasal bridge, low posterior hairline) and digital anomalies. Congenital heart malformations, visual and hearing impairment, urogenital abnormalities and seizures have also been reported.
A rare form of congenital myopathy characterised by global muscle weakness, hypotonia, myotonia and cramps in the presence of cylindrical, spiral-shaped inclusions (located in the central and/or subsarcolemmal areas of muscle fibres) in skeletal muscle biopsy. Abnormal gait, scoliosis, epileptic encephalopathy and psychomotor delay may be associated.
A rare chromosomal anomaly syndrome with a highly variable phenotype. Manifestations range from minor anomalies with normal development to intrauterine growth retardation, abnormal skin pigmentation, craniofacial and body asymmetry, cardiac (ventricular septal defect) and genital (hypospadias, cryptorchidism) anomalies, scoliosis and hearing loss to neonatal death. Additional features observed include skeletal malformations (clino/polydactyly, talipes), mild facial dysmorphism, and developmental delay.
A rare chromosomal anomaly syndrome with a highly variable phenotype. Principle characteristics are intrauterine growth restriction, growth and motor delay, craniofacial dysmorphism (microcephaly, hypertelorism, micro/anophthalmia, midface hypoplasia, cleft lip/palate), congenital heart and neural tube defects, as well as various skeletal (scoliosis, radioulnar hypoplasia, preaxial polydactyly) and gastrointestinal (intestinal malrotation, Hirschsprung disease) anomalies. Central nervous system malformations (including ventriculomegaly, thin corpus callosum, spina bifida) have also been reported.
A rare chromosomal anomaly syndrome with high phenotypic variability. Manifestations range from a mild phenotype presenting joint pain and laxity, mild facial dysmorphism (long facies, prominent eyes, dysplastic ears, downturned corners of the mouth, micrognathia) and no developmental delays to more severe phenotypes including short stature, intellectual disability, severe developmental delays, additional craniofacial dysmorphic features (brachycephaly, high forehead, flat midface, short neck) and hearing impairment, as well as skeletal (pectus excavatum, scoliosis), ocular (coloboma) and cardiac abnormalities.
An extremely rare autosomal anomaly resulting from the presence of 4 copies of chromosome 21. The disease is characterised by features of trisomy 21 including developmental delay/intellectual disability, muscular hypotonia, short neck with redundant skin, brachycephaly, microcephaly, flat face, epicanthus, upslanted palpebral fissures, small ears, protruding tongue, single transverse palmar crease, brachydactyly, hypoplastic iliac wings, together with additional features such as prematurity, intrauterine growth retardation, high and broad forehead, hypertelorism. Haematological malignancies are also associated and may occur earlier than in trisomy 21.
A rare form of hereditary spastic paraplegia with characteristics of childhood (exceptionally adolescent) onset of a complex phenotype presenting with lower limb (followed by upper limb) spasticity with hyperreflexia and extensor plantar responses, with additional manifestations including progressive dysarthria, dystonia, mild cognitive decline, extrapyramidal features, optic atrophy and seizures. White matter abnormalities and brain iron accumulation have also been observed on brain magnetic resonance imaging.
A rare partial monosomy of the short arm of chromosome 17 with a variable phenotype. The disease has characteristics of prenatal and postnatal growth retardation, developmental delay, mild intellectual disability, macrocephaly, mild facial dysmorphism including prominent forehead, hypertelorism, thick upper and/or lower lip vermillion and structural abnormalities of the brain variably including white matter abnormalities, prominent Virchow-Robin spaces, Chiari I malformation, corpus callosum hypoplasia but not lissencephaly.
A rare chromosomal anomaly syndrome, resulting from a partial interstitial micro duplication of the short arm of chromosome 7. The disease has characteristics of intellectual disability, psychomotor and speech delay, craniofacial dysmorphism (including macrocephaly, frontal bossing, hypertelorism, abnormally slanted palpebral fissures, anteverted nares, low-set ears, microretrognathia) and cryptorchidism. Cardiac (patent foramen ovale and atrial septal defect), as well as renal, skeletal and ocular abnormalities may also be associated.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome X, characterised by global developmental delay, autistic behaviour, microcephaly and facial dysmorphism (including down-slanting palpebral fissures, depressed nasal bridge, anteverted nares, long philtrum, down-slanting corners of the mouth). Seizures have also been reported in some patients.
A rare chromosomal anomaly syndrome resulting from a partial interstitial deletion of the short arm of chromosome 9. The disease has characteristics of mild to moderate developmental delay, hand tremors, myoclonic jerks, attention deficit-hyperactivity disorder and a social personality. Patients also present bruxism, short stature and minor facial dysmorphic features (bilateral epicanthic folds, broad, flat nasal bridge, anteverted nares, low-set ears micro/retro-gnathia).
A rare mitochondrial oxidative phosphorylation disorder due to nuclear deoxyribonucleic acid anomalies. The disease is characterised by progressive external ophthalmoplegia without diplopia, cerebellar atrophy, proximal skeletal muscle weakness with generalised muscle wasting, profound emaciation, respiratory failure, spinal deformity and facial muscle weakness (manifesting with ptosis, dysphonia, dysphagia and nasal speech). Intellectual disability, gastrointestinal symptoms (nausea, abdominal fullness, and loss of appetite), dilated cardiomyopathy and renal colic have also been reported.
A rare cancer of corpus uteri composed of squamous cells of varying degree of differentiation that usually affects postmenopausal women and presents with abnormal vaginal discharge, dysfunctional bleeding, abdominal pain and distension. It is often associated with cervical stenosis and pyometra.
A chromosomal condition occurring when a piece of the long (q) arm of chromosome 18 is missing near the center of the chromosome. The disease has a wide range of characteristics including developmental delay, intellectual disability, delayed expressive language skills, recurrent seizures and hypotonia. Macrocephaly may also be associated along with characteristic facial features including prominent forehead, ptosis, downslanting palpebral fissures, puffy periorbital tissue, and full cheeks. Most cases of proximal 18q deletion syndrome are the result of a new (de novo) deletion and are not inherited from a parent.
A rare complex hereditary spastic paraplegia with childhood to adolescent onset of progressive lower limb spasticity, associated with mild to severe gait disturbances, extensor plantar responses, muscle weakness and severe distal atrophy, frequently with upper limb involvement. Additional features may include joint contractures, distal sensory loss and brisk or absent deep tendon reflexes. Other signs, such as depression, memory loss, optic atrophy (with vision loss) and brain iron deposition (revealed by brain imagery) have also been reported.
A rare parasitic disease characterised by the infestation of natural body cavities with dipteran larvae. Clinical presentation is variable depending on the affected site(s) and degree of infestation and include foreign-body sensation (with or without movement sensation), haemorrhage, pain, oedema, sensory loss, malodour, and pruritus, among others. Neurological features (motor deficits, seizures, reduced mental status, extrapyramidal signs) have been reported in cerebral myiasis.
A rare inherited neuromuscular disease with prenatal presentation (usually in the second trimester) of reduced fetal movements and abnormal positioning. This results in joint abnormalities that may involve both lower and upper extremities and is usually symmetric. Also associated with severe hypotonia at birth, bilateral club foot, motor development delay, mild facial weakness without ophthalmoplegia, absent deep tendon reflexes, normal motor and sensory nerve conduction velocities, no cerebellar or pyramidal involvement and progressive disease course with loss of ambulation after the first decade of life.
On assessment the patient is determined to be physically prepared to undergo surgery.
On assessment the patient is determined to be psychologically prepared to undergo surgery.
A rare form of axonal peripheral sensorimotor neuropathy with characteristics of classical Charcot-Marie-Tooth type 2 signs and symptoms (progressive weakness and atrophy of distal limb muscles, mild sensory deficits of position, vibration and pain/temperature, pes cavus, and symmetrically absent or reduced muscle and sensory action potentials with relatively preserved nerve conduction velocities in neurophysiological studies) as well as pyramidal tract involvement (spasticity, hyperreflexia). Spasticity and pain may be the presenting symptoms.
A subtype of Autosomal dominant Charcot-Marie-Tooth disease type 2 with the childhood onset of distal weakness and areflexia (with earlier and more severe involvement of the lower extremities), reduced sensory modalities (primarily pain and temperature sensation), foot deformities, postural tremor, scoliosis and contractures. Optic atrophy, vocal cord palsy with dysphonia, sensorineural hearing loss, spinal cord abnormalities and hydrocephalus have also been reported.
A subtype of acute myeloid leukaemia with recurrent genetic abnormalities, characterised by clonal proliferation of myeloid blasts harbouring somatic mutations of the CEBPA gene in the bone marrow, blood and rarely other tissues. It can present with anaemia, thrombocytopenia, and other nonspecific symptoms related to ineffective haematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly).
A rare subtype of renal cell carcinoma, occurring in the context of end-stage kidney disease and acquired cystic kidney disease, characterised by a usually well circumscribed, solid, multifocal, bilateral tumour with inter or intracellular micro lumen formation (leading to cribiform architecture). Tumours are often diagnosed incidentally in early stages, although complications caused by renal cysts (dull flank or abdominal pain, fever) or renal parenchymal bleeding may mask the underlying neoplastic process. Most have an indolent behaviour.
A rare genetic dysostosis syndrome with marked inter and intra-familial variation with typical characteristics of triphalangeal thumbs, hand and/or foot polysyndactyly and/or absent/hypoplastic tibiae (associated with duplication of fibulae in some cases), although isolated triphalangeal thumbs have also been reported. It is often accompanied with remarkable short stature and additional features may include radio-ulnar synostosis and hand oligodactyly, as well as abnormal carpal and metatarsal bones.
The non-syndromic form of a primary immunodeficiency disease characterised by deficient gamma globulins and associated predisposition to frequent and recurrent infections from infancy. Two forms have been described: X-linked represents approximately 85% of the affected patients, and autosomal which includes recessive and dominant cases but is far less frequent. The clinical signs of the two forms are very similar and include recurrent bacterial infections, diarrhoea and skin infections with onset in infancy. Defects in B lymphocyte development and maturation appear to underlie agammaglobulinaemia. Mutations in seven genes have been reported to be related to IA: BTK (Xq21.33-q22), BLNK (10q23.2-q23.33), CD79A (19q13.2), CD79B (17q23), IGHM(14q32.33), IGLL1 (22q11.23), PIK3R1 (5q13.1) and TCF3 (19p13.3).
A rare malignant haematologic disease characterised by clonal proliferation of myeloid blasts, primarily involving the bone marrow, in association with congenital disorders (e.g. Fanconi anemia, dyskeratosis congenita, Bloom syndrome, Down syndrome, congenital neutropenia, neurofibromatosis) and genetic defects predisposing to acute myeloid leukaemia. Patients present with signs and symptoms related to ineffective haematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement (gingivitis, splenomegaly). Depending on the underlying genetic defect, there may be additional cancer risks and other health problems present.
A rare genetic developmental defect during embryogenesis with characteristics of a range of developmental eye anomalies (including anophthalmia, microphthalmia, colobomas, microcornea, corectopia, cataract) and symmetric limb rhizomelia with short stature and contractures of large joints. Intellectual disability with autistic features, macrocephaly, dysmorphic features, urogenital anomalies (hypospadia, cryptorchidism), cutaneous syndactyly and precocious puberty may also be present.
A rare mitochondrial disorder due to a defect in mitochondrial protein synthesis characterised by severe intrauterine growth retardation, neonatal limb oedema and redundant skin on the neck (hydrops), developmental brain defects (corpus callosum agenesis, ventriculomegaly), brachydactyly, dysmorphic facial features with low set ears, severe intractable neonatal lactic acidosis with lethargy, hypotonia, absent spontaneous movements and fatal outcome. Markedly decreased activity of complex I, II + III and IV in muscle and liver have been determined.
A rare genetic neuromuscular disorder characterised by proximal and symmetrical muscle weakness (particularly of neck, sternomastoid, facial and diaphragm muscles), spinal rigidity, joint contractures (Achilles tendon, elbows, hands), generalised muscle hypertrophy and early respiratory failure (usually in the first decade of life). Patients typically present delayed motor milestones and grossly elevated serum creatine kinase levels, and with disease progression, forced expiratory abdominal squeeze and nocturnal hypoventilation.
A rare genetic skeletal muscle disease with characteristics of neonatal hypotonia, distal more than proximal muscle weakness, progressive exercise intolerance with prominent myalgias, and mild-to-moderate overall motor impairment with preserved ambulation. Face, extraocular, cardiac, and respiratory muscles are unaffected. Mild cognitive impairment is also noted in most patients.
A rare multiple congenital anomalies syndrome characterised by psychomotor delay, severe intellectual deficit, severe muscle hypoplasia (with absence of subcutaneous fatty tissue), generalised contractures, craniofacial dysmorphic features (dolichocephaly, esotropia, ears of unequal size, high palate), chest and spinal deformities (sternum shifted to side, kyphoscoliosis), pulmonary anomalies (unilateral hypoplastic bronchial system), arachnodactyly, and genital abnormalities (cryptorchidism, hypospadias, testicular agenesis). Repeated respiratory tract infections and atelectasis are also associated. There have been no further descriptions in the literature since 1970.
A rare non-syndromic congenital heart malformation with characteristics of the prolapse of an aortic valve cusp into a subjacent ventricular septal defect due to Venturi effect, resulting in aortic regurgitation. Patients typically present with symptoms of progressive aortic valve insufficiency, such as shortness of breath, heart palpitations and chest pain and exercise intolerance.
A rare primary bone dysplasia with characteristics of a Larsen-like phenotype including multiple, congenital, large joint dislocations, craniofacial abnormalities (macrocephaly, flat occiput, prominent forehead, hypertelorism, low-set, malformed ears, flat nose, cleft palate), spinal abnormalities, cylindrical fingers, and talipes equinovarus, as well as growth retardation (resulting in short stature) and delayed bone age. Other reported clinical manifestations include severe developmental delay, hypotonia, clinodactyly, congenital heart defect and renal dysplasia.
An isolated focal, hereditary palmoplantar keratoderma with characteristics of linear hyperkeratosis along the flexor aspect of the fingers and on palms, as well as focal hyperkeratosis of the plantar skin. Patients present with painful thickening of the skin on palms and soles with occasional fissuring, blistering and hyperhidrosis. Rarely, hyperkeratosis on other areas may be seen (knees, dorsal aspects of the digits). Histopathologically widened intercellular spaces between keratinocytes are observed.
A rare genetic chronic primary adrenal insufficiency disorder due to partial loss-of-function CYP11A1 mutations. The disease has characteristics of early-onset adrenal insufficiency without associated abnormal external male genitalia. Patients present with signs of adrenal crisis, including electrolyte abnormalities, severe weakness, recurrent vomiting and seizures. Ultrasound reveals absent (or very small) adrenal glands.
A rare inherited mitochondrial disorder due to a defect in mitochondrial protein synthesis. The disease has characteristics of intrauterine growth retardation, metabolic decompensation with recurrent vomiting, persistent severe lactic acidosis, encephalopathy, seizures, failure to thrive, severe global developmental delay, poor eye contact, severe muscular hypotonia or axial hypotonia with limb hypertonia, hepatomegaly and/or liver dysfunction and/or liver failure, leading to fatal outcome in severe cases. Neuroimaging abnormalities may include corpus callosum thinning, leukodystrophy, delayed myelination and basal ganglia involvement.
Rare infectious encephalitis characterized by an acute onset of neurological signs and symptoms (altered consciousness, seizures, headaches, meningeal signs, behavioral changes) due to bacterial infection by Mycoplasma pneumoniae. Patients typically present unspecific signs and symptoms such as fever, nausea, vomiting, fatigue prior to onset of neurological manifestations and frequently have a history of a respiratory tract infection (pneumonia, bronchiolitis, pharyngitis).
A very rare form of focal palmoplantar keratoderma with characteristics of painful circumscribed hyperkeratotic lesions on weight-bearing areas of soles, moderate focal hyperkeratosis of palmar pressure-related areas and an asymptomatic leukokeratosis confined to labial and lingual attached gingiva. Additional occasional features may include hyperhidrosis, follicular keratosis and extended oral mucosa involvement.
Biallelic mutation carriers have a mutation (not necessarily the same mutation) in both copies of a particular gene (a paternal and a maternal mutation). The RPE65 gene provides instructions for making an enzyme that is essential for normal vision and mutations in this gene result in reduced or absent levels of RPE65 activity, blocking the visual cycle and resulting in impaired vision. Almost all patients eventually progress to complete blindness.
A rare subtype of renal cell carcinoma characterised histologically by tubular architecture and sheets of spindle cells embedded in a mucinous/myxoid stroma and macroscopically by a solid, generally well-circumscribed, partially encapsulated tumour of variable size, with a homogenously coloured, bulging cut surface. Occasionally containing areas of haemorrhage or necrosis, usually located in the cortex. Patients can present abdominal/flank pain, abdominal mass and/or haematuria, however most are asymptomatic and tumour is discovered incidentally. Indolent behaviour is frequent and association with nephrolithiasis and end-stage kidney disease had been noted.
A rare myofibrillar myopathy with characteristics of slowly progressive, proximal skeletal muscle weakness, which is initially more prominent in lower extremities and involves upper extremities with disease progression. Patients present with difficulty climbing stairs, a waddling gait, marked winging of scapula, lower back pain, paresis of limb girdle musculature, hypo or areflexia and/or mild facial muscle weakness in rare cases. Respiratory muscle weakness is common and cardiac anomalies (conduction blocks, tachycardia, diastolic dysfunction, left ventricular hypertrophy) have been reported in some cases.
A rare congenital non-dystrophic mild slowly progressive proximal myopathy characterised by exercise intolerance and post-exercise myalgia without rhabdomyolysis, associated with highly organised hexagonally cross-linked tubular arrays in skeletal muscle biopsy. Additional features may include muscle atrophy (or diffuse hypotrophy), myalgia with or without muscular weakness, paresis of truncal and limb-girdle musculature, minimal ptosis, lumbar hyperlordosis, decreased deep tendon reflexes, contractures and pes equinovarus.
A rare chromosomal anomaly disorder resulting from the partial duplication of the proximal long arm of chromosome 13 with a highly variable phenotype. The disease is principally characterised by increased polymorphonuclear leucocyte projections and persistence of fetal haemoglobin, growth and developmental delay and craniofacial dysmorphism (including microcephaly, depressed nasal bridge, stubby nose, low-set, malformed ears, cleft lip/palate, micrognathia). Strabismus, clinodactyly and undescended testes in males may also be associated.
A rare chromosomal anomaly syndrome resulting from the partial trisomy of the long arm of chromosome 9. The disease has a highly variable phenotype principally characterised by developmental delay, short stature, intellectual disability and craniofacial dysmorphism (microcephaly, broad forehead, low set ears, epicanthus, prominent nose and retrognathia). Cardiac, ocular, thyroid and oesophagus defects along with central nervous system and behavioural/psychiatric abnormalities have also been reported.
A rare neuro inflammatory/neuro autoimmune disease with characteristics of acute (or subacute) onset of disturbance of consciousness (occasionally presenting as convulsions) and high fever associated with cerebral lesions (on magnetic resonance imaging) that are restricted to the limbic system (particularly the hippocampi and amygdalae), in the absence of viral, bacterial, fungal, paraneoplastic and other disorders.
A rare neuroendocrine neoplasm arising from neural crest-derived paraganglion cells (most often in the para-aortic region at the level of renal hilii, organ of Zuckerkandl, thoracic paraspinal region, bladder and carotid body) not associated with catecholamine secretion. These neoplasms are usually clinically silent and symptoms if present are nonspecific and depend on the location of the neoplasm. Association with certain hereditary cancer-predisposing syndromes, such as multiple endocrine neoplasia, neurofibromatosis type 1 or von Hippel lindau syndrome may be observed.
An inherited disorder that increases the risk of a variety of malignant and benign tumors most commonly occurring in the skin, eyes, kidneys, chest, abdomen and mesothelium. Affected individuals can develop one or more types of neoplasm and affected members of the same family can have different types. Malignancies arise at a younger age, are often more aggressive and tend metastasize. The disease is caused by mutations in the BAP1 gene. In addition to a germline mutation in one copy of the gene, a second somatic mutation usually occurs in the normal copy of the gene in cells that give rise to neoplasms. Together, the germline and somatic mutations result in a complete loss of BAP1 protein function in tumor cells. Inherited in an autosomal dominant pattern, in most cases, an affected person has one parent with the condition. People with a mutation in the BAP1 gene inherit an increased risk of tumor formation however not all will develop a tumor.
A pure or complex form of hereditary spastic paraplegia with characteristics of onset in the first decade of life of spastic paraparesis (more prominent in lower than upper extremities) and unsteady gait, as well as increased deep tendon reflexes, amyotrophy, cerebellar ataxia and flexion contractures of the knees in some.
A subtype of autosomal dominant Charcot-Marie-Tooth disease type 2 with characteristics of late adult-onset (50-60 years of age) of slowly progressive, axonal, peripheral sensorimotor neuropathy resulting in distal upper limb and proximal and distal lower limb muscle weakness and atrophy, in conjunction with distal, pan modal sensory impairment in upper and lower limbs. Tendon reflexes are reduced and nerve conduction velocities range from reduced to absent. Neuropathic pain has also been associated.
A rare genetic neurological disorder with early infantile-onset of seizures, borderline to moderate intellectual disability, cerebellar features including dysarthria and ataxia and cerebellar atrophy and cortical thickening observed on MRI imaging. Seizures are typically focal (with prominent eye blinking, facial and limb jerking), precipitated by fever and often commence with an oral sensory aura. When not properly controlled by anti-epileptic medication, weekly frequency and persistence into adult life is observed.
A rare genetic neurological disorder characterised by late childhood onset of slowly progressive cerebellar ataxia. Initial manifestations include weakness and atrophy of distal limb muscles, areflexia and loss of pain, vibration and touch sensations in upper and lower extremities. Gaze nystagmus, cerebellar dysarthria, peripheral neuropathy, steppage gait and pes cavus develop as disease progresses. Cerebellar atrophy (especially of the vermis) is present in all affected individuals. Additional reported manifestations include seizures, mild brain atrophy, mild hypercholesterolaemia and borderline hypoalbuminaemia.
Rare genetic epilepsy characterised by speech disorder (including a range of symptoms from dysarthria, speech dyspraxia, receptive and expressive language delay/regression and acquired aphasia to subtle impairments of conversational speech) and epilepsy (mostly focal and secondary generalised childhood-onset seizures, sometimes with aura). Mild to severe intellectual disability may also be observed.
A type of isolated punctate hereditary palmoplantar keratoderma with characteristics of multiple asymptomatic 1 to 2 mm-long, firm, hyperkeratotic projections (spiny keratosis) on the palms, soles and digits (typically confined to their volar and/or lateral aspects). Histopathologically compact columnar parakeratosis over hypo or agranular epidermis is observed.
A rare progressive dermis disorder with characteristics of thickening of the scalp resulting in redundancy of skin which gives rise to folds and grooves that give the scalp a cerebriform appearance. Folds cannot be corrected by pressure or traction and typically are symmetric and extend anteroposteriorly from vertex to occiput and/or transversely in occipital region. Additional features may include mild subungual hyperkeratosis and distal onycholysis of the nail plates of the great toes. It is not associated with neurological and ophthalmological changes or with secondary causes.
A rare inborn error of metabolism disease with characteristics of mild to moderate persistent elevation of methylmalonic acid in plasma, urine and cerebrospinal fluid. Clinical presentation may include acute metabolic decompensation with metabolic acidosis (presenting with vomiting, dehydration, confusion, hallucinations), nonspecific neurological symptoms or the disease may also be asymptomatic.
A rare maternal disease-related embryofetopathy with characteristics of variable developmental anomalies of the fetus due to teratogenic effect of elevated maternal body temperature (resulting from febrile illness or hot environment exposure). Reported developmental anomalies include neural tube defects (spina bifida, encephalocele, anencephaly), cardiac defects (transposition of great vessels), urogenital defects (hypospadias), abdominal wall defects, cleft lip/palate, eye defects (cataract, coloboma) or various minor anomalies (for example bifid uvula, preauricular pit or tag). Consensus regarding cause and effect relationship has not been reached.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the short arm of chromosome 8 with a highly variable phenotype. Principle characteristics are mild to moderate developmental delay, intellectual disability, mild facial dysmorphism (including prominent forehead, arched eyebrows, broad nasal bridge, upturned nares, cleft lip and/or palate) and congenital cardiac anomalies (atrioventricular septal defect). Other reported features include macrocephaly, attention deficit disorder, seizures, hypotonia and ocular and digital anomalies (poly or syndactyly).
A rare normolipemic non-Langerhans cell histiocytosis characterised by progressive growth of multiple to disseminated asymptomatic skin lesions that range in appearance from yellow plaques to coalescence-prone red-brown papules, nodules and pedunculated tumours up to 5 cm in size, located typically on the face, trunk and extremities (and rarely on conjunctiva and mucous membranes). Characteristic microscopic findings include a storiform spindle cell infiltrate in the deep dermis with xanthoma macrophages and some Touton cells in the upper dermis. It is usually not associated with systemic disease.
A rare chromosomal anomaly syndrome resulting from a partial duplication of the short arm of chromosome 16. The disease has characteristics of developmental delay and intellectual disability of a highly variable degree, autism spectrum, obsessive-compulsive, attention deficit hyperactivity disorder, speech articulation abnormalities, muscular hypotonia, tremor, hyper or hyporeflexia, seizures, microcephaly, neuroimaging abnormalities, decreased body mass index and schizophrenia or bipolar disorder later on in life.
Isolated non-familial catecholamin-producing tumors arising from neuroendocrine chromaffin cells in the adrenal medulla or in extra-adrenal chromaffin tissue, respectively. The majority of these tumors are benign and the presenting symptoms are typically caused by the increased catecholamine production of the tumor, including hypertension (often paroxysmal), tachycardia, anxiety and/or excessive sweating.
A form of severe combined immunodeficiency (SCID) characterised by severe and recurrent infections, associated with diarrhoea and failure to thrive. The disease manifests during the first months of life with severe and often life threatening viral, bacterial or fungal and failure to thrive. Chronic diarrhoea is a frequent finding. Some patients may have skin rashes and abnormalities of liver function. Immunological findings are lymphopenia with the absence of T and NK cells, hypogammaglobulinaemia, and normal or increased B cell count. The disease results from a defect in the IL2RG gene encoding the common gamma chain and transmission is X-linked.
A rare genetic T cell negative B cell negative severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial microorganisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins, some patients may have eosinophilia.
A rare benign sex cord-stromal neoplasm with a typically unilateral location in the ovary. The disease has characteristics of mixed features of both fibroma and thecoma. Patients may be asymptomatic or may present with pelvic/abdominal pain and/or distension and occasionally, with post-menopausal bleeding. Large neoplasms of greater than 10cm are often associated with pleural effusion and ascites (Meig syndrome triad).
A rare inherited skin hyperpigmentation disorder with characteristics of widespread lentigines without associated noncutaneous abnormalities. Patients present multiple brown to dark brown, non-elevated macula of 0.2 to 1 cm in diameter, spread over the entire body, sometimes including palms or soles, but never oral mucosa.
A rare late adult-onset myofibrillar myopathy with characteristics of progressive distal muscle weakness associated with peripheral neuropathy and hyporeflexia. Ambulation may be lost within a few years.
Disease with characteristics of variable degrees of muscle weakness due to progressive skeletal myopathy sometimes associated with dilated cardiomyopathy or left ventricle dilation. Duchenne and Becker muscular dystrophies primarily affect males and only a small percentage of female carriers have been reported to manifest these diseases. Symptomatic female carriers usually present later in life, muscle weakness is generally mild to moderate and is usually proximal and asymmetric, some patients present with cardiac manifestations alone. Females with clinical features are usually carriers of X-chromosome rearrangements, display skewed X-inactivation or have Turner syndrome.
A rare benign neoplasm of the central nervous system characterised by the development of multiple or rarely solitary meningioma in two or more blood relatives without other apparent syndromic manifestations. Depending on the localisation, growth rate and size of the tumours, patients can present with subtle, gradually worsening or abrupt and severe neurological compromise or can be completely asymptomatic.
Disorder with an extremely variable clinical presentation characterised by the presence of partial to complete, congenital, fibrous, circumferential, constriction bands/rings on any part of the body, although a particular predilection for the upper or lower extremities is seen. Phenotypes range from only a mild skin indentation to complete amputation of parts of the fetus (for example digits, distal limb). Compression from the rings may lead to oedema, skeletal anomalies (for example fractures, foot deformities) and infrequently neural compromise.
A rare neurologic disease with characteristics of the triad of optic ataxia, ocular apraxia and simultanagnosia due to posterior parietal lobe lesions. Patients report ophthalmologic difficulties in the absence of underlying ophthalmologic anomalies and present severe visual and spatial disabilities in locating and reaching objects, initiating voluntary eye movements and perceiving more than one object at a time.
A form of non-Langerhans cell histiocytosis with characteristics of cutaneous presentation of solitary or disseminated yellow to orange-brown papular or papulonodular, noncoalescent, asymptomatic skin lesions located predominantly on the head, neck, trunk and extremities (rarely on oral mucosa), in the presence of normal lipid levels. Microscopically, the lesions consist of monomorphous infiltrate of xanthoma macrophages and numerous Touton giant cells, with scant or absent inflammatory infiltrate. It is usually not associated with systemic disease.
A rare genetic male infertility with characteristics of azoospermia resulting from a mutation in a single gene known to cause azoospermia. Sperm morphology may be normal.
A rare genetic male infertility due to oligozoospermia (number of sperm in the ejaculate inferior to 15 million/mL) resulting from a mutation in a single gene known to cause oligozoospermia. Sperm morphology may be normal.
Rare syndrome with the association of the features of Waardenburg Shah and neurological features namely neonatal hypotonia, intellectual deficit (of variable severity), nystagmus, progressive spasticity, ataxia and epilepsy. Autonomic dysfunction (reduced saliva production, sweating and tearing, and bradycardia and arrhythmia) may also be present. Delayed white matter myelination is present on brain MRI, and may also be responsible for neuropathy at the peripheral level. Hirschsprung disease is sometimes absent. Most of the cases are caused by mutations involving the SOX10 gene (22q13.1): either a large deletion or point mutation located in the last two exons.
Disease that is characterised by severe microcytic anaemia, B-cell lymphopenia, panhypogammaglobulinaemia and variable neurodegeneration. The disease presents in infancy with recurrent febrile illnesses, gastrointestinal disturbances, developmental delay, seizures, ataxia and sensorineural deafness. Most patients require regular blood transfusion, iron chelation, and intravenous immunoglobulin replacement. Stem cell transplantation has been reported to be successful. Caused by homozygous or compound heterozygous mutation in the TRNT1 gene on chromosome 3p26.
Classical mycosis fungoides is the most common type of mycosis fungoides, a form of cutaneous T-cell lymphoma, and is characterised by slow progression from patches to more infiltrated plaques and eventually to tumours. The disease first manifests by skin lesions consisting of flat patches, preferentially located asymmetrically on the buttocks and other sun-protected areas (lower trunk and thighs, and the breasts in women). In the later stages of the disease, infiltrated plaques and red-violet, dome-shaped tumours or generalised erythroderma may develop. Lymph nodes are the most frequent site of extracutaneous involvement. Visceral involvement (liver, lung, and bone marrow) may also occur. The aetiology remains unknown.
A group of mitochondrial DNA maintenance syndrome diseases with characteristics of predominantly neuromuscular manifestations with typically infantile onset of hypotonia, lactic acidosis, psychomotor delay, progressive hyperkinetic-dystonic movement disorders, external ophthalmoplegia, sensorineural hearing loss, seizures and variable renal tubular dysfunction. It may be associated with a broad range of other clinical features.
A neurological disorder with characteristics of moderate to severe developmental delay and intellectual disability and mild dysmorphic features. Early symptoms include hypotonia, delayed development of motor skills, speech delay, hypertelorism, broad nasal bridge, and fingers with tapered ends. Other features include microcephaly, seizures, recurrent ear infections, strabismus, amblyopia and hyperopia. Behavioral problems such as hyperactivity, attention deficit disorder, aggression, anxiety and autism spectrum occur in some cases. Caused by mutations in the HIVEP2 gene leading to a shortage of functional HIVEP2 protein. Inherited in an autosomal dominant pattern however most cases of this condition result from de novo mutations in the gene.
A rare chromosomal anomaly syndrome with highly variable phenotype. Principal characteristics are intrauterine growth retardation, failure to thrive, developmental delay, hypotonia, mild dysmorphic features (including microcephaly, short forehead, upslanting palpebral fissures, hypertelorism, epicanthal folds, wide nasal bridge, broad nasal tip, long philtrum, thin upper lip, micrognathia, short neck), skeletal anomalies (for example kyphosis, brachydactyly, clinodactyly, talipes equinovarus) and dermatological features (including cafe-au-lait spots). Patients may also present ventriculoseptal defects and genital abnormalities (for example genital hypoplasia, phimosis, cryptorchidism).
A rare chromosomal anomaly syndrome with a highly variable phenotype. Principle characteristics are pre and postnatal growth retardation, short stature, developmental delay, mild to severe intellectual disability, microcephaly and mild dysmorphic features (including triangular face, dysplastic ears, upslanting palpebral fissures, epicanthic folds, broad nasal bridge, full nasal tip, long philtrum, downturned corners of the mouth, and micro/retrognathia). Additional manifestations reported include hypotonia, mild articular limitation, hearing loss, digital anomalies (clinodactyly, brachydactyly), cafe au lait patches and hypospadias.
A rare chromosomal anomaly syndrome with a highly variable phenotype. Principle characteristics are a neonatal mewing cry, severe developmental delay and intellectual disability, short stature, hypotonia, dysmorphic features (including microcephaly, facial asymmetry, hypertelorism, epicanthal folds, abnormal ears, micro/retrognathia), congenital cardiac anomalies (such as atrial and ventricular septal defect, tricuspid insufficiency, hypoplastic aorta) and skeletal abnormalities (for example hypoplastic thumbs, anomalous ulna/radius, dysplastic metacarpals and phalanges).
A rare subtype of mixed epithelial-mesenchymal tumor, often presenting as a large, exophytic polypoid lesion, which may extend through the cervix, composed of benign or atypical epithelium and low-grade malignant stroma. It usually presents with dysfunctional bleeding or vaginal discharge and less frequently abdominal pain. Association with long-term unopposed estrogen therapy, tamoxifen therapy and a history of pelvic radiation has been reported.
A rare epithelial carcinoma arising either in the gallbladder itself or from the epithelium lining the extrahepatic biliary tree, cystic duct and/or peribiliary gland. The disease has characteristics of nonspecific symptoms, such as abdominal pain, jaundice and vomiting and sometimes mimicking benign biliary diseases. Chronic biliary epithelial inflammation (for example primary sclerosing cholangitis, cholelithiasis, choledocholithiasis, liver fluke infestation) is a major risk factor.
A rare hereditary motor and sensory neuropathy characterised by intermediate motor median nerve conduction velocities (usually between 25 and 45 m/s) and signs of both demyelination and axonal degeneration in nerve biopsies. It presents with usual clinical features of Charcot-Marie-Tooth disease (progressive muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, and feet deformities) in the first to second decade of life with steady progression until the fourth decade, severe progression and stabilisation afterwards.
A rare hereditary motor and sensory neuropathy with characteristics of intermediate motor median nerve conduction velocities (usually between 25 and 45 m/s) and signs of both demyelination and axonal degeneration in nerve biopsies. It presents with mild to moderately severe, slowly progressive usual clinical features of Charcot-Marie-Tooth disease (muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, and feet deformities). Other findings include asymptomatic neutropenia and early-onset cataracts.
A rare hereditary motor and sensory neuropathy characterised by intermediate motor median nerve conduction velocities (usually between 25 and 60 m/s). It presents with moderately severe, slowly progressive usual clinical features of Charcot-Marie-Tooth disease (muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, feet deformities, extensor digitorum brevis atrophy). Findings in nerve biopsies include age-dependent axonal degeneration, reduced number of large myelinated fibres, segmental remyelination, and no onion bulbs.
A rare hereditary motor and sensory neuropathy with characteristics of intermediate motor median nerve conduction velocities (usually between 25 and 45 m/s) and signs of both axonal degeneration and demyelination without onion bulbs in nerve biopsies. It presents with usual Charcot-Marie-Tooth disease clinical features of variable severity (progressive muscle weakness and atrophy of the distal extremities, distal sensory loss, reduced or absent deep tendon reflexes, and feet deformities). Other findings in some of the families include debilitating neuropathic pain and mild postural/kinetic upper limb tremor.
A rare acquired aplastic anaemia characterised by a severe normocytic anaemia with normal peripheral leukocyte and platelet counts, reticulocytopenia, high serum ferritin and transferrin saturation levels and isolated, almost complete absence of erythroblasts in the bone marrow with normal granulopoiesis and megakaryopoiesis. It presents with signs of severe anaemia (fatigue, lethargy, pallor, intolerance of physical exercise and exertional dyspnoea) in the absence of haemorrhagic symptoms.
A rare congenital vascular anomaly syndrome characterised by venous or on occasion arterial malformations that lead to soft tissue hypertrophy and bone hypoplasia. An affected limb is generally shortened, highly deformed, painful and oedematous with associated bone and muscle hypotrophy. Single parts or multiple small parts of limbs are typically affected but more extensive involvement including complete extremity shoulder girdle and axilla have been reported.
A rare neurologic disorder with characteristics of a unique non-REM and REM parasomnia with sleep breathing dysfunction, gait instability and repetitive episodes of respiratory insufficiency, as well as autoantibodies against IgLON5. Patients may present stridor, chorea, limb ataxia, abnormal ocular movements, and bulbar symptoms (such as dysphagia, dysarthria, episodic central hypoventilation) with normal brain MRI. Excessive day sleepiness and cognitive deterioration have also been reported.
A rare pure or complex form of hereditary spastic paraplegia with characteristics of onset in infancy of progressive lower limb spasticity, abnormal gait, increased deep tendon reflexes and extensor plantar responses that may be associated with intellectual disability. Additional signs such as contractures in the lower limbs, amyotrophy, clubfoot and optic atrophy, have also been reported. Caused by homozygous mutation in the NT5C2 gene on chromosome 10q24.
A rare infantile epilepsy syndrome with characteristics of benign afebrile seizures in previously healthy infants and children (age range 1 month to 6 years) with mild acute gastroenteritis without any central nervous system infection, severe dehydration, or electrolyte imbalances. In most cases the seizures are tonic-clonic with focal origin on EEG, occur between day 1 and 6 following onset of acute gastroenteritis, cease within 24 hours and do not persist after the illness.
A rare cerebral malformation due to abnormal neuronal migration defined as a cerebral cortex with many excessively small convolutions. It presents with developmental delay, intellectual disability, seizures and various neurological impairments and may be isolated or comprise a clinical feature of many genetic syndromes. It may also be associated with perinatal cytomegalovirus infection.
A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of developmental delay, intellectual disability, thin habitus with narrow shoulders, mesomelic shortness of the arms, craniofacial dysmorphism (for example long lower face, maxillary hypoplasia, beak nose, short columella, prognathia, high arched palate, obtuse mandibular angle), brachydactyly (mostly involving middle phalanges) and cardiovascular anomalies (such as aortic root dilatation, mitral valve prolapse).
Rare congenital anomaly of the great veins with characteristics of absence of the left brachiocephalic vein (or innominate vein), resulting in an anomalous venous vasculature. Patients are usually asymptomatic and the anomaly is typically discovered intraoperatively. An association with persistence of left superior vena cava, permanent levoatrial cardinal vein or anomaly of the inferior vena cava has been reported in some cases.
Rare childhood-onset epilepsy syndrome associated with infection and a biphasic clinical course. The initial symptom is a prolonged febrile seizure on day 1 (the first phase). Afterwards, patients have variable levels of consciousness from normal to coma. Irrespective of the consciousness levels, magnetic resonance imaging (MRI) during the first 2 days shows no abnormality. During the second phase (usually days 4 - 6), patients show a cluster of seizures and deterioration of consciousness. Diffusion-weighted images (DWI) on MRI reveal the brain lesions with reduced diffusion predominantly in the subcortical white matter. After the second acute phase, consciousness levels improve with the emerging focal neurological signs. Neurological outcomes vary from normal to mild or severe sequelae including cerebral atrophy, mental retardation, paralysis and epilepsy.
A subgroup of therapy-related myeloid neoplasms (t-MN), associated with treatment of an unrelated neoplastic disease with cytotoxic agents, like etoposide, doxorubicin, daunorubicin and others. The neoplastic cells often show rearrangements involving the mixed lineage leukaemia gene at 11q23. This subgroup of t-MN is typically associated with overt leukaemia, without preceding myelodysplastic syndrome, developing 2-3 years after exposure, presenting with non-specific symptoms related to ineffective haematopoesis (fatigue, bleeding and bruising, recurrent infections, bone pain) and/or extramedullary site involvement.
A subgroup of therapy-related myeloid neoplasms (t-MN), associated with treatment of an unrelated neoplastic disease with radiation. The neoplastic cells typically harbor unbalanced aberrations of chromosomes 5 and 7 (monosomy 5/del(5q) and monosomy 7/del(7q)) or a complex karyotype. Patients frequently present with multilineage dysplasia and cytopenias 5-10 years after exposure.
A rare variant of Guillain-Barre syndrome characterised by acute onset monophasic sensory neuropathy with diminished or absent tendon reflexes, loss of proprioception, positive Romberg sign and nerve conduction features of demyelination. It presents several weeks after acute infection with paraesthesia, ataxia and neuropathic pain.
A rare chromosomal anomaly syndrome characterised by pre and postnatal growth restriction, developmental delay, variable degrees of intellectual disability, hand and foot anomalies (for example brachy/clinodactyly, talipes equinovarus, nail hypoplasia, proximally placed digits) and mild craniofacial dysmorphism (including microcephaly, triangular face, broad nasal bridge, micrognathia). Neonatal lymphoedema, heart malformations, aplasia cutis congenita, aortic root dilatation and autistic spectrum disorder have also been reported.
A rare chromosomal anomaly syndrome with a variable phenotype. Principally characteristics are intellectual disability, developmental delay, short stature, craniofacial dysmorphism (including microcephaly, low posterior hairline, frontal bossing, bitemporal narrowing, low-set and malformed ears, flat nasal bridge, long philtrum, wide mouth with downturned corners, thin upper lip) and a short, webbed neck, as well as skeletal anomalies (e.g. brachy rhizomelia, poly/syndactyly) and joint hyperlaxity. Cardiac, cerebral, and urogenital anomalies are also frequently associated.
A rare chromosomal anomaly syndrome with characteristics of low birth weight, developmental delay, intellectual disability, short stature, craniofacial dysmorphism (including microcephaly, midface hypoplasia, hypertelorism, flat nasal bridge, ear anomalies, short philtrum, downturned corners of the mouth, micrognathia) and a short neck with redundant skin folds. Additional features may include hypotonia, skeletal anomalies (for example clino/camptodactyly), seizures and congenital cardiac, urogenital and gastrointestinal malformations.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the short arm of chromosome 1. The disease has characteristics of borderline to mild intellectual disability, mild developmental delay, metopic craniosynostosis and mild craniofacial dysmorphism (including sloping forehead, bitemporal narrowing, blepharophimosis). Other associated abnormalities may include growth retardation, microcephaly, large hands, syndactyly, supernumerary ribs, rectal stenosis and/or anterior displacement of anus. Congenital heart malformations (for example atrial septal defect, patent ductus arteriosus) have also been reported.
Maternal uniparental disomy of chromosome 2 is an uniparental disomy of maternal origin that most likely does not have any phenotypic expression except from cases of homozygosity for a recessive disease mutation for which only mother is a carrier.
Maternal uniparental disomy of chromosome 4 is an uniparental disomy of maternal origin that most likely does not have any phenotypic expression except from cases of homozygosity for a recessive disease mutation for which only mother is a carrier.
Maternal uniparental disomy of chromosome 6 is a uniparental disomy of maternal origin with manifestation of intrauterine growth retardation. Homozygosity for a recessive disease mutation for which only a mother is a carrier may lead to other phenotypes.
Maternal uniparental disomy of chromosome 9 is an uniparental disomy of maternal origin that most likely does not have any phenotypic expression except from cases of homozygosity for a recessive disease mutation for which only mother is a carrier.
A rare variant of multiple sclerosis with characteristics of a rapidly progressive, aggressive form of multiple sclerosis with numerous large multifocal demyelinating lesions in deep white matter on cerebral MRI that usually leads to severe disability or death within weeks to months without remission. A relapsing form of multiple sclerosis is observed in surviving patients.
A rare cancer of corpus uteri derived from neural crest cells with characteristics of small, round neoplastic cells with variable degree of neural, glial and ependymal differentiation. Macroscopically, the tumor is often a large, poorly circumscribed polypoid mass with necrotic areas and hemorrhage. It usually presents with lower abdominal or pelvic pain, irregular vaginal bleeding or discharge, pelvic mass and uterine enlargement.
A rare cancer of cervix uteri derived from neural crest cells, histologically composed of small, round neoplastic cells with variable degree of neural, glial and ependymal differentiation. Macroscopically, the tumor is often a large, soft, poorly circumscribed mass with infiltrative borders and necrotic areas. It presents with dysfunctional vaginal bleeding or discharge, lower abdominal pain and uterine enlargement.
An extremely rare anorectal malformation syndrome with characteristics of imperforate anus, closed ano-perineal fistula, preauricular skin tag and absent renal abnormalities and pre-axial limb deformities. There have been no further descriptions in the literature since 1983.
A rare juvenile idiopathic inflammatory myopathy characterised by the association of inflammatory myositis (manifesting with acral erythema, progressive weakness of the limbs, pain, general fatigue, moodiness or crankiness) with clinical and/or laboratory features of other autoimmune diseases (for example systemic lupus erythematosus, localised scleroderma, diabetes). Cardiac involvement has been reported in some patients.
A rare auto inflammatory syndrome defined as recurrence of pericardial inflammation of unknown origin following the first episode of acute pericarditis and a symptom-free interval of 4-6 weeks or longer. Recurrent attacks of chest pain may be the sole presentation or chest pain may be accompanied by pericardial friction rub, electrocardiographic or echocardiographic changes, pericardial effusion and increased C-reactive protein. Cardiac tamponade is a rare life-threatening complication.
A rare inflammatory myopathy characterised by diffuse destructive infiltration of CD68 positive macrophages into the fascia rather than muscle fibres in muscle biopsies, proximal muscle weakness and myalgia with or without scaly dermatomyositis-like or atypical non-dermatomyositis-like skin lesions, elevation of creatine kinase levels and thickening of muscle fascia in muscle MRI.
A rare cancer-predisposing syndrome associated with the D1 subgroup of Fanconi anaemia characterised by progressive bone marrow failure, cardiac, brain, intestinal or skeletal abnormalities and predisposition to various malignancies. Bone marrow suppression and the incidence of developmental abnormalities are less frequent than in other Fanconi anaemia, but cancer risk is very high with the spectrum of childhood cancers including Wilms tumour, brain tumour (often medulloblastoma) and acute lymphoblastic leukaemia /acute myeloid leukaemia.
Isochromosomy Yp is a rare gonosome anomaly characterised by various clinical presentations including normal healthy fertile males, male phenotype with infertility, and males with ambiguous genitalia or incomplete masculinisation.
A rare non-syndromic cerebellar malformation characterised by an underdeveloped cerebellar vermis. Patients may present a variable phenotype ranging from normal neurodevelopment to motor and/or language delay, variable degrees of cognitive impairment, hypotonia, equilibrium disturbances, static/dynamic ataxia, oculomotor abnormalities, epilepsy and/or clumsiness. Behavioural disorders such as attention deficit hyperactivity disorder and generalised anxiety have also been reported. Brain MRI may reveal diffuse or selective (mostly posterior) vermian cerebellar hypoplasia and EEG may show focal paroxysms.
A rare genetic non-syndromic cerebral malformation due to abnormal neuronal migration disorder characterised by variable-sized, focalised malformations located in any part(s) of the cerebral cortex, which manifests with drug-resistant epilepsy (usually leading to intellectual disability) and behavioural disturbances. Abnormal MRI findings (for example abnormal white and/or grey matter signal, blurred grey-white matter junction, localised volume loss, cortical thickening, abnormal gyral pattern, abnormal hippocampus) and variable histopathologic patterns are associated.
A rare rheumatologic disease characterised by predominantly bilateral, chronic, sterile inflammation and progressive sclerosis and hyperostosis of the sternocostoclavicular joint, with adjacent soft tissue ossification, in the absence of other joint involvement. It presents as recurrent episodes of pain, oedema and/or erythema of the sternoclavicular region. Palmoplantar pustulosis may be additionally observed in some cases.
A rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 13. Principle characteristics are global developmental delay, mild intellectual disability, obesity and mild craniofacial dysmorphism (microcephaly, wide rectangular forehead, downslanting palpebral fissures, mild ptosis, prominent nose with long nasal bridge and broad tip, small chin). Other variable reported features include congenital heart defects, hand and foot anomalies (for example polydactyly) and agenesis of the corpus callosum.
A rare primary bone dysplasia disorder with characteristics of normal or mild short stature, early-onset pain and/or stiffness of the joints (mainly affecting knees but also elbows, wrists, ankles and fingers, with relative sparing of the hips) and early degenerative joint disease. Other skeletal anomalies (including varus or valgus deformities, osteochondritis dissecans, abnormal carpal shape, free articular bodies) and mild myopathy have also been reported.
Paternal uniparental disomy of chromosome 1 is a uniparental disomy of paternal origin that most likely does not have any phenotypic expression except from cases of homozygosity for a recessive disease mutation for which only the father is a carrier.
Paternal uniparental disomy of chromosome 21 is a uniparental disomy of paternal origin that most likely does not have any phenotypic expression except from cases of homozygosity for a recessive disease mutation for which only the father is a carrier.
Paternal uniparental disomy of chromosome 7 is an uniparental disomy of paternal origin that most likely do not have any phenotypic expression except from cases of homozygosity for a recessive disease mutation for which only father is a carrier (for example cystic fibrosis, congenital chloride diarrhea, sensorineural hearing loss).
A rare variant of Guillain-Barre syndrome with characteristics of isolated leg weakness, areflexia and radicular leg pain that may simulate a cauda equina or spinal cord syndrome. The arms, ocular, facial, and oropharyngeal muscles are spared and sphincteric function is normal.
A rare cardiovascular morphological anomaly due to maldevelopment of embryonal aorta resulting in right aortic arch and left ligamentum arteriosum characterised by tracheooesophageal compression symptoms (stridor, dyspnoea, dysphagia, apnoeic episodes, recurrent respiratory infections).
A rare congenital anomaly of the great veins with characteristics of an anomalous course of the left brachiocephalic vein, passing from left to right below the aortic arch and entering the superior vena cava below the orifice of the azygos vein. Patients are frequently asymptomatic and diagnosed incidentally on imaging studies. Other cardiac malformations may be associated.
A rare cancer of corpus uteri presenting as a large, polypoid, intraluminal mass with necrosis, composed of small to intermediate-size, relatively uniform, dyshesive cells displaying no differentiation. It usually presents with dysfunctional bleeding or vaginal discharge and, less often, abdominal pain. Association with Lynch syndrome was reported.
A rare vulvovaginal neoplasm, a highly malignant soft tissue sarcoma composed of cells with round to oval or spindle-shaped nuclei and eosinophilic cytoplasm that may show differentiation towards striated muscle cells. It usually affects children and presents with a vulvar or vaginal mass that may be polypoid or grape-like (embryonal subtype) and associated with bleeding and ulceration.
A rare chromosome X structural anomaly with a highly variable phenotype. Principle characteristics are developmental delay, intellectual disability, short stature, craniofacial dysmorphism (including microcephaly, facial asymmetry, hypertelorism, long palpebral fissures, epicanthus, low-set or malrotated ears, broad nose with a flat nasal bridge, anteverted nares, long philtrum, thin upper lip, high arched palate, micrognathia) and skeletal anomalies (for example cubitus valgus, talipes equinovarus). Patients may also present heart malformations (for example ventricular septal defects, mitral valve stenosis), sacral dimple, soft tissue syndactyly, pigmented nevi and seizures.
A rare genetic developmental defect during embryogenesis syndrome with characteristics of the association of complete, partial or submucous cleft palate and ankyloglossia. Patients may also present abnormal uvula (for example absent, bifid, shortened or laterally deviated), short lingual frenulum and dental anomalies (for example buccal crossbite, absent and/or misshapen teeth). Digital abnormalities, such as mild clinodactyly and/or syndactyly, have also been reported.
A rare distal hereditary motor neuropathy with characteristics of slowly progressive atrophy and weakness of distal muscles of hands and feet with normal deep tendon reflexes or absent ankle reflexes and minimal or no sensory loss, sometimes mild proximal weakness in the legs and feet and hand deformities in males.
A rare chromosomal anomaly syndrome resulting from the partial deletion of the short arm of chromosome 1. The disorder has characteristics of developmental delay, corpus callosum agenesis/hypoplasia and craniofacial dysmorphism, such as macrocephaly (caused by hydrocephalus or ventriculomegaly), low-set ears, anteverted nostrils and micrognathia. Urinary tract defects (for example vesicoureteral reflux, urinary incontinence) are also frequently associated. Other reported variable manifestations include hypotonia, tethered spinal cord, Chiari type I malformation and seizures.
An extremely rare complex hereditary spastic paraplegia with characteristics of infancy or childhood onset of global developmental delay and progressive spasticity with tremor in the distal limbs, increased deep tendon reflexes and extensor plantar responses, which may be associated with mild intellectual disability. Additional features include muscle wasting and cerebellar abnormalities.
An extremely rare syndromic hair shaft anomaly with characteristics of sparse, coarse, brittle, excessively dry and slow-growing scalp hair, sparse axillary and pubic hair, sparse or absent eyelashes and eyebrows and dry skin. Hair shaft analysis shows pili torti, longitudinal splitting, grooves, peeling and scaling. There have been no further descriptions in the literature since 1987.
A rare hereditary ataxia with characteristics of progressive cerebellar ataxia associated with disruption of visual fixation by saccadic intrusions. It presents with progressive gait, trunk and limb ataxia with pyramidal tract signs (increased tendon reflexes and Babinski sign), myoclonic jerks, fasciculations, cerebellar dysarthria, sensorimotor axonal neuropathy with impaired joint position, vibration, temperature, pain sensations, pes cavus, and saccadic intrusions with characteristic overshooting horizontal saccades, macrosaccadic oscillations, and increased velocity of larger saccades, without other eye movement disturbances.
A rare epilepsy syndrome characterised by absence seizures with perioral myoclonia as the main seizure type, accompanied by generalised tonic-clonic seizures, appearing before or together with absences. Consciousness is usually impaired, although to variable degree. Commonly observed absence status epilepticus, poor response to antiepileptic drugs and persistence of seizures into adulthood, in the presence of normal neurological status and intelligence, are additional clinical features of this syndrome.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 2, primarily characterised by global developmental delay, hypotonia, autistic-like features and behavioural problems. Craniofacial dysmorphism (arched eyebrows, hypertelorism, bilateral ptosis, prominent nose, wide mouth, micro/retrognathia) and an affable personality are also commonly associated. Minor digital anomalies (fifth finger clinodactyly and large, broad first toe) have occasionally been reported.
A rare genetic endocrine growth disease resulting from growth hormone secretagogue receptor (GHSR) deficiency. The disease has characteristics of postnatal growth delay that results in short stature. The pituitary gland is typically without morphological changes, although anterior pituitary gland hypoplasia has been reported.
A rare hereditary ataxia with characteristics of delayed early motor development, severe neonatal hypotonia, non-progressive ataxia and slow eye movements, presenting normal cognitive abilities and absence of pyramidal signs. Frequently patients also manifest intention tremor, mild dysphagia, and dysarthria. Brain MRI reveals global cerebellar atrophy with absence of other malformations or degenerations of the central and peripheral nervous systems.
A rare genetic primary bent bone dysplasia characterised by significant, uni/bilateral, lateral tibial bowing localised to the distal two-thirds of the tibia, with respective cortical thickening and thinning of the inner and outer tibial curve, loss of normal trabecular bone, bilateral abnormalities of the tibial epiphyses and growth plates, as well as foot abnormalities, including abnormally high arches. Affected individuals have short stature with absence of other skeletal abnormalities.
A rare genetic primary bone dysplasia disorder with characteristics of disproportionate short stature with shortening of upper and lower limbs, short and broad fingers with short hands, narrowed chest with rib abnormalities and pectus excavatum, abnormal chondral calcifications (including larynx, trachea and costal cartilages) and facial dysmorphism (frontal bossing, hypertelorism, prominent eyes, short flat nose, wide nostrils, high-arched palate, long philtrum). Platyspondyly (especially of cervical spine) and abnormal epiphyses and metaphyses are observed on radiography. Atlantoaxial instability causing spinal compression and recurrent respiratory disease are potential complications that may be lethal.
A rare multiple congenital anomalies/dysmorphic syndrome with characteristics of developmental delay, intellectual disability, short stature, sensorineural hearing impairment, facial dysmorphism (including epicanthus, broad, depressed nasal bridge, broad, fleshy nasal tip, mildly anteverted nares, deep nasolabial folds, broad mouth with thin upper lip) and skeletal anomalies (including abnormally placed thumbs, brachydactyly, scoliosis, dysplastic carpal bones). Severe behavior disturbances (aggression, hyperactivity), as well as hypopigmented skin lesions and hypoplastic digital patterns are also associated. There have been no further descriptions in the literature since 1992.
A rare genetic non-syndromic cerebral malformation with characteristics of severe intellectual disability, progressive postnatal microcephaly, axial hypotonia, spastic quadriparesis, seizures and facial dysmorphism (bushy eyebrows, hairy forehead, broad nasal root, long flat philtrum, V-shaped upper lip). Additionally, talipes equinovarus, non-obstructive cardiomyopathy, persistent hyperplastic primary vitreous, obstructive hydrocephalus and autistic features may also be associated. On brain magnetic resonance imaging, the 'butterfly sign' is characteristically observed and cortical calcifications, agenesis of the corpus callosum, ventriculomegaly, brainstem dysplasia and cerebellar vermis hypoplasia have also been described.
A rare parkinsonian syndrome due to intoxication which develops in individuals surviving an acute cyanide intoxication episode or due to chronic exposure to small cyanide doses. It presents several weeks after acute exposure with progressive typical clinical features of parkinsonism including bradykinesia, rigidity, dystonia, hypomimia, hypokinetic dysarthria, postural instability and retropulsion but no resting or postural tremor. Brain MRI reveals bilateral lesions in the pallidum, posterior putamen, substantia nigra, subthalamic nucleus, temporal and occipital cortex and cerebellum.
A rare genetic primary bone dysplasia disorder with characteristics of early-onset severe lumbar kyphosis, marked brachydactyly and irregular, pronounced cone epiphyses of the metacarpals and phalanges. Additional reported features include developmental delay, intellectual disability, hypotonia, epileptic seizures and mild facial dysmorphism (including long and thin or square-shaped face, slight mid-face hypoplasia, hypertelorism, epicanthic folds, low-set ears, anteverted nostrils). Radiographic findings also reveal hypoplasia of iliac wings and anterior defect of vertebral bodies.
A rare mitochondrial disorder due to a defect in mitochondrial protein synthesis with characteristics of neonatal onset of severe metabolic acidosis and respiratory distress, persistent lactic acidosis with episodes of metabolic crises, developmental regression, microcephaly, abnormal gaze fixation and pursuit, axial hypotonia with limb spasticity and reduced spontaneous movements. Neuroimaging studies reveal polymicrogyria, white matter abnormalities and multiple cystic brain lesions, including basal ganglia, and cerebral atrophy. Decreased activity of complex I and IV have been determined in muscle biopsy.
A rare combined T and B cell immunodeficiency with characteristics of susceptibility to develop an aggressive, childhood-onset, disseminated, cutaneous and systemic Kaposi sarcoma. There is evidence the disease is caused by homozygous mutation in the OX40 gene (TNFRSF4) on chromosome 1p36.
A rare familial dilated cardiomyopathy with characteristics of left ventricular enlargement and/or reduced systolic function preceded or accompanied by significant conduction system disease and/or arrhythmias including bradyarrhythmias, supraventricular or ventricular arrhythmias. Disease onset is usually in early to mid-adulthood. Sudden cardiac death may occur and may be the presenting symptom. In some cases, it is associated with skeletal myopathy and elevated serum creatine kinase.
A rare genetic cranial malformation with characteristics of unilateral or bilateral synostosis of the lambdoid suture in multiple members of a single family. Unilateral cases typically present ipsilateral occipitomastoid bulge, compensatory contralateral parietal and frontal bossing, displacement of one ear, lateral deviation of jaw and compensatory deformation of cervical spine while bilateral cases usually manifest with flat and widened occiput, displacement of both ears and frequent occurrence of raised intracranial pressure.
A rare breast malformation with characteristics of the presence, in various members of a single family, of one or more nipple(s) and/or their related tissue, in addition to the normal bilateral chest nipples. The anomaly is usually situated along the embryonic milk line, from axillae to inguinal regions, but other locations are also possible. Association with dental abnormalities, Becker nevus, renal or underlying breast tissue malignancy and genitourinary malformations has been reported.
A rare genetic skin disease characterised by multiple milium-like, comedone-like lesions and skin-coloured to hyperpigmented, 1 to 2 mm-sized papules, associated with hypotrichosis and palmar/plantar pits. Lesions are usually first noticed on cheeks or neck and gradually increase in size and number to involve the scalp, face, ears, shoulders, chest, axillae and upper arms. In severe cases, lower back, lower arms, and back of the legs can be involved. Mild hypohidrosis has also been reported.
A rare biological anomaly defined as high serum ferritin levels without elevations of transferrin saturation, tissue or serum iron and with characteristics of an apparently asymptomatic clinical phenotype.
A rare cancer of the uterine cervix composed of nests of large neoplastic cells with ""ground glass"" cytoplasm, surrounded by a stroma with prominent eosinophilic infiltrates. It is a poorly differentiated, aggressive variant of adenosquamous carcinoma that usually affects young women and presents with dysfunctional vaginal bleeding and lower abdominal pain. Distant metastases to the lungs, liver spleen or bones are often present at the time of diagnosis. It is often associated with high-risk Human papillomavirus infection (types 18, 16 and 32).
A rare genetic limb malformation syndrome with characteristics of multiple congenital distal joint contractures (including talipes equinovarus and both proximal and distal interphalangeal joint contractures of the hands) and very severe motor paralysis at birth (such as lack of swallowing, autonomous respiratory function and deep tendon reflexes), leading to death within first 3 months of life. Fetal hypo or akinesia, late-onset polyhydramnios and dramatically reduced, or absent, motor nerve conduction velocities are frequently associated. Nerve ultrastructural morphology shows severe abnormalities of the nodes of Ranvier and myelinated axons.
A rare cerebral malformation with epilepsy syndrome characterised by early-onset gelastic (ictal laughter) or dacrystic (ictal crying) seizures due to non-neoplastic developmental malformation - hypothalamic hamartomas. In many patients, seizures progress to other seizure types including focal and generalised seizures, with concomitant cognitive decline and behavioural disorders. Some patients also present a precocious puberty.
A rare inflammatory eye disease of unknown aetiology characterised by generalised inflammation of the uvea (iris, ciliary body, choroid), retina and vitreous with consequent ciliary spasm and posterior synechiae formation, leading to acute or chronic, unilateral or bilateral visual impairment and ocular discomfort or pain. Patients present an increased risk of development of cataracts, secondary glaucoma, cystoid macular oedema and/or retinal detachment. It could potentially result in vision loss.
A rare non-syndromic cerebellar malformation with characteristics of loss of volume in the right or left cerebellar hemisphere, with intact vermis and no other neurological anomalies (normal cerebral hemispheres, fourth ventricle, pons, medulla and midbrain). Patients may be asymptomatic or may present developmental and speech delay, hypotonia, abnormal ocular movements, persistent headaches and/or peripheral vertigo and ataxia. Neurological examination is otherwise normal.
A rare genetic hypertension with characteristics of a familial severe hypertension with an onset before age 20 years, associated with suppressed plasma renin and low aldosterone levels in the presence of low or normal levels of the mineralocorticoid aldosterone, that is highly resistant to antihypertensive medication. During pregnancy, there is a marked exacerbation of hypertension, accompanied by low serum potassium levels and undetectable aldosterone levels, but without signs of preeclampsia, requiring early delivery.
A rare congenital heart malformation with characteristics of tetralogy of Fallot (pulmonary stenosis, overriding aorta, ventricular septal defect and right ventricular hypertrophy), complete absence or rudimentary pulmonary valve that is both stenotic and regurgitant and an absence of the ductus arteriosus. It presents prenatally with cardiomegaly, polyhydramnios, fetal heart failure, hydrops fetalis and fetal demise or postnatally with cyanosis and respiratory failure due to bronchomalacia secondary to bronchial compression from dilated pulmonary arteries. It is frequently associated with 22q11 deletion.
A rare axonal hereditary motor and sensory neuropathy with early onset (less than 10 years) progressive distal muscle weakness and wasting of the lower limbs and later, to a lesser extent the upper limbs resulting in foot and wrist drop, areflexia, skeletal deformities (kyphoscoliosis, pes cavus with flattening, joint contractures), mild sensory impairment with vibration sense reduced to a greater extent than pain, optic atrophy and hearing loss. Wheelchair dependence by adolescence is usual and respiratory impairment with diaphragmatic paralysis may develop.
A rare hepatic and biliary tract tumor, arising either in the gallbladder itself or in the epithelium lining the extrahepatic biliary tree, the cystic duct and peribiliary glands. It is characterized by a substantial keratinization with abundant keratohyalin pearls and central deposition of dense keratin material within infiltrative nests and locally aggressive nature. In the early stages of the disease symptoms are vague and nonspecific (abdominal pain, jaundice and vomiting). In the advanced stages it may present with a bulky tumor and symptoms of adjacent organ involvement.
An extremely rare malignant epithelial tumor of the small intestine (most often localized in the duodenum). Presenting symptoms are often nonspecific, such as weight loss, epigastric pain, anorexia, weakness, fatigue, vomiting and abdominal distension, and vary depending on localization of the tumor. Gastrointestinal bleeding and perforation may occur in advanced cases.
An array of conditions related to the stress of throwing in children and young adolescents.
A rare genetic immunodeficiency due to a complement cascade protein anomaly characterised by low or undetectable serum ficolin 3 levels, susceptibility to infections and possibly autoimmunity. The presentation is variable, from perinatal necrotising enterocolitis and recurrent skin infections with Staphylococcus aureus to childhood-onset recurrent pulmonary infections leading to brain abscesses and pulmonary fibrosis, to membranous nephropathy. In some patients clinical consequences of ficolin 3 deficiency were not clear. There is evidence that ficolin 3 deficiency is caused by homozygous mutation in the FCN3 gene on chromosome 1p36.
Type 2 is much more severe than Type I, cyanosis is accompanied by neurological dysfunction with intellectual deficit, microcephaly, growth retardation, opisthotonus, strabismus and hypertonia, which usually becomes evident during the first four months of life. Caused by global loss of Cb5R function.
In type 1 cyanosis from birth is the only symptom, it is well tolerated and is associated with mild complaints of headaches, fatigue and shortness of breath upon exertion. Caused by mutations of the CYB5R3 gene (22q13.31-qter) encoding the NADH-cytochrome b5 reductase (Cb5R) and Cb5R deficiency is limited to the erythrocytes.
Describes a posterior tooth relationship bilaterally where the posterior teeth are in crossbite on both the right and left side.
A deep overbite resulting in the mandibular teeth impinging on and stripping the oral mucosa from the lingual of the maxillary teeth.
A microdeletion occurring on the short (p) arm of chromosome 16 at a location designated p12.2. Common characteristics of this disease include developmental delay, delayed speech, intellectual disability, hypotonia, short stature, microcephaly, cardiac malformations, recurrent epilepsy, psychiatric and behavioral problems. Manifestations vary even among affected members of the same family. Inherited in an autosomal dominant pattern with incomplete penetrance, in almost all known cases the chromosomal change has been inherited from a parent
Syndrome with manifestations of intellectual disability and delayed development of speech and motor skills with expressive language skills generally more severely affected. Individuals may be unable to speak, learn to walk later or may never walk. In infancy hypotonia and feeding difficulties may be present along with dysphagia, hypersomnolence, hypothermia and hypoventilation. Recurrent seizures are common. Caused by mutations in the PURA gene, which provides instructions for the protein Pur-alpha. This protein has multiple roles in cells, including gene transcription and replication of DNA. The disease is inherited in an autosomal dominant pattern, however most cases result from de novo mutation.
Hypermanganesemia with dystonia is an inherited disorder in which excessive amounts of the element manganese accumulate in the body (hypermanganesemia). One place manganese builds up in particular is in a region of the brain responsible for the coordination of movement, causing neurological problems that make controlling movement difficult. Consequently, the condition is characterized by involuntary, sustained muscle contractions (dystonia) and other uncontrolled movements. Two types of hypermanganesemia with dystonia, called hypermanganesemia with dystonia, polycythemia, and cirrhosis (HMDPC) and hypermanganesemia with dystonia 2, have been identified. They are distinguished by their genetic causes and certain specific features.In HMDPC (also known as hypermanganesemia with dystonia 1), manganese accumulates in the blood, brain, and liver. Signs and symptoms of the condition can begin in childhood (early-onset), typically between ages 2 and 15, or in adulthood (adult-onset). Most children with the early-onset form of HMDPC experience dystonia in the arms and legs, which often leads to a characteristic high-stepping walk described as a ""cock-walk gait."" Other neurological symptoms in affected children include involuntary trembling (tremor), unusually slow movement (bradykinesia), and slurred speech (dysarthria). The adult-onset form of HMDPC is characterized by a pattern of movement abnormalities known as parkinsonism, which includes bradykinesia, tremor, muscle rigidity, and an inability to hold the body upright and balanced (postural instability).Individuals with HMDPC have an increased number of red blood cells (polycythemia) and low levels of iron stored in the body. Additional features of HMDPC can include an enlarged liver (hepatomegaly) due to manganese accumulation in the organ, scarring (fibrosis) in the liver, and irreversible liver disease (cirrhosis).In hypermanganesemia with dystonia 2, manganese accumulates in the blood and brain. Signs and symptoms of this type of the disorder usually begin between ages 6 months and 3 years. Development of motor skills, such as sitting and walking, may be delayed, or if already learned, they may be lost. Dystonia can affect any part of the body and worsens over time. By late childhood, the sustained muscle contractions often result in joints that are permanently bent (contractures) and an inability to walk unassisted. Some affected individuals have an abnormal curvature of the spine (scoliosis). People with hypermanganesemia with dystonia 2 can have other neurological problems similar to those in HMDPC, such as tremor, bradykinesia, parkinsonism, and dysarthria. Unlike in HMDPC, individuals with hypermanganesemia with dystonia 2 do not develop polycythemia or liver problems.
Syndrome with characteristics of infancy onset hypotonia, feeding difficulties, breathing problems, dysphagia, severely delayed development of speech and motor skills, distinctive facial features, recurrent seizures and seizure-like episodes (muscle jerking, twitching, and stiffening). Brain abnormalities may also be present several of which are caused by reduced production of myelin or delayed maturation of myelin. Caused by a microdeletion occurring on the long (q) arm of chromosome 5 at a position designated q31.3. The deleted region typically contains at least three genes. The loss of one of these genes, PURA, is thought to lead to most of the characteristic features of the condition. The condition is not inherited.
An immunodeficiency disorder with onset in infancy that leads to recurrent, severe infections of the respiratory tract. Infections are most frequently caused by rhinovirus. Respiratory syncytial virus and the influenza virus may also cause recurrent infections. Infection may require hospital admission and repeated infection can lead to chronic lung disease. Infections usually become less frequent with maturity. Caused by mutations in the IFIH1 gene, which provides instructions for making the MDA5 protein. Deficiency of MDA5 protein activity reduces interferon production in response to RNA-containing viruses. The inheritance pattern is unclear. In some cases, the condition seems to follow an autosomal recessive pattern, in other cases it appears that the condition is inherited in an autosomal dominant pattern.
A neurological disorder with characteristics of moderate to severe developmental delay and intellectual disability. Additional manifestations may include hypotonia, delayed development of motor skills, delayed speech development, recurrent seizures, autism spectrum disorder, macrocephaly and unusual facial features including frontal bossing, hypertelorism and downslanting palpebral fissures. Caused by mutations in the PPP2R5D gene, which provides instructions for making B56-delta resulting in the production of an altered B56 protein. Inherited in an autosomal dominant pattern however most cases of this condition result from de novo gene mutation.
A single anterior tooth pair is in crossbite and is also impinging on the soft tissue, resulting in destruction of the oral mucosa adjacent to one or both teeth involved.
Serous cystadenoma of childhood is a benign epithelial ovarian neoplasm with characteristics of a usually unilateral, cystic, unilocular or multilocular lesion with a thin wall or septa and no intracystic solid portion on imaging. It often presents with abdominal pain or an asymptomatic abdominal mass and can be associated with ovarian torsion or malignant transformation.
Mucinous cystadenoma of childhood is a benign epithelial ovarian neoplasm with characteristics of a usually unilateral, cystic, unilocular or multilocular lesion with a thin wall or septa and no intracystic solid portion on imaging. It often presents with abdominal pain or an asymptomatic abdominal mass and can be associated with ovarian torsion or malignant transformation.
A rare tumor of cranial and spinal nerves arising from peripheral nerve sheath and composed exclusively or predominantly of cells showing perineurial differentiation. It presents as a well-circumscribed, rarely encapsulated mass, not associated with a recognizable nerve, most commonly arising in the dermis and subcutis of the extremities or trunk, or, rarely, in deep soft tissue or skin (for example in the stomach, kidney, pancreas, maxillary sinus, mandible, bronchial tree and the face). The clinical presentation depends on the localization.
A rare chromosomal anomaly syndrome resulting from the partial duplication of the long arm of chromosome 1. The syndrome has a highly variable phenotype and principle characteristics of intellectual disability, short stature, craniofacial dysmorphism (including macro/microcephaly, prominent forehead, posteriorly rotated, low-set ears, abnormal palpebral fissures, microphthalmia, broad, flat nasal bridge, high-arched palate, micro/retrognathia), cardiac defects and urogenital anomalies. Patients may also present cerebral (for example ventriculomegaly) and gastrointestinal malformations, as well as dystonic tremor and recurrent respiratory tract infections.
A rare otorhinolaryngologic disease with characteristics of the unilateral or bilateral dehiscence of the bone(s) overlying the superior (most common), lateral or posterior semicircular canal(s). Patients present audiological (autophony, aural fullness, conductive hearing loss, pulsatile tinnitus) and/or vestibular symptoms (sound or pressure-evoked oscillopsia or vertigo, characteristic vertical-torsional eye movements), depending on which semicircular canal is affected. Posterior SCD syndrome is associated with high-riding jugular bulb and fibrous dysplasia, while lateral SCD syndrome is associated with chronic otitis media and cholesteatoma, with or without audiological and vestibular symptoms.
An extremely rare, benign or malignant germ cell tumor characterized, clinically, by a teratoma presenting in an extragonadal location (for example retroperitoneum, mediastinum, craniofacial or sacrococcygeal region, intraosseous, solid organs) and histologically by displaying well-differentiated structures as well as immature elements. Presenting symptoms are variable depending on size and location of tumor.
A genetic non-syndromic congenital malformation of the neurenteric canal, spinal cord and column characterized by progressive neurologic deterioration (pain, sensorimotor deficits, abnormal gait, decreased tone or abnormal reflexes), musculoskeletal changes (foot deformities and asymmetry, muscle atrophy, limb weakness and numbness, gait disturbances, scoliosis) and/or genitourinary manifestations (bladder and bowel dysfunction). Midline cutaneous stigmata in the lumbosacral region, such as turfs of hair, skin appendages, dimples, subcutaneous lipomas, skin discoloration or hemangiomas, are frequently associated.
Benign condition with purple-colored patches, plaques or nodules, usually found bilaterally on the extensor surfaces of the lower extremities and associated with chronic venous insufficiency and arteriovenous malformations. A reactive angiodysplasia of preexisting cutaneous blood vessels that resembles malignant conditions like Kaposi's sarcoma and requires histopathological examination for its diagnosis and differentiation.
Tooth requires a dental crown due to weakened and limited natural tooth remaining.
A disorder of the nervous system white matter and myelin resulting in hypomyelination and in some cases also demyelination. There are different combinations of signs and symptoms of the disease, at the most severe end of the spectrum is hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). At the mildest end is isolated hypomyelination. The features in other individuals with TUBB4A-related leukodystrophy fall in between these two extremes. The disease is caused by mutations in the TUBB4A gene, which provides instructions for making a protein called beta-tubulin. Inherited in an autosomal dominant pattern however most cases are the result of de novo mutations in the gene.
Tooth requires a dental crown due to weakened and limited natural tooth remaining from previous large restoration.
An imbalance between proinflammatory and anti-inflammatory responses to an infection.
Lower anterior facial height is proportionally greater than normal when compared with upper anterior facial height.
Lower anterior facial height is proportionally less than normal when compared with upper anterior facial height.
Vertical bone deficiency in the posterior region of alveolar ridge, which is a contributing factor to the development of a short vertical dimension of the face.
Vertical bone excess in the posterior region of the alveolar ridge, which is a contributing factor to the development of a long vertical dimension of the face. Over-eruption of posterior teeth is observed.
Atransferrinemia is characterized by microcytic anemia and by iron loading. It can be treated effectively by plasma infusions (summary by Beutler et al., 2000).
Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders characterized by congenital nonprogressive joint contractures, with a worldwide incidence of 1 in 3,000 live births. AMC can occur in the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth (summary by Markus et al., 2012). There is also a distal form of arthrogryposis multiplex congenita (see DA1A, 108120) and a lethal congenital form (see LCCS1, 253310).
Collagen type VI-related disorders represent a continuum of overlapping phenotypes with Bethlem myopathy at the mild end, Ullrich congenital muscular dystrophy (CMD) at the severe end, and two rare, less well-defined disorders – autosomal dominant limb-girdle muscular dystrophy and autosomal recessive myosclerosis myopathy – in between. Although Bethlem myopathy and Ullrich CMD were defined long before their molecular basis was known, they remain useful for clarification of prognosis and management. Bethlem myopathy, characterized by the combination of proximal muscle weakness and variable contractures, affects most frequently the long finger flexors, elbows, and ankles. Onset may be prenatal (characterized by decreased fetal movements), neonatal (hypotonia or torticollis), in early childhood (delayed motor milestones, muscle weakness, and contractures), or in adulthood (proximal weakness and Achilles tendon or long finger flexor contractures). Because of slow progression, more than two thirds of affected individuals over age 50 years rely on supportive means for outdoor mobility. Respiratory involvement is rare and appears to be related to more severe muscle weakness in later life. Ullrich CMD is characterized by congenital weakness and hypotonia, proximal joint contractures, and striking hyperlaxity of distal joints. Some affected children acquire the ability to walk independently; however, progression of the disease often results in later loss of ambulation. Early and severe respiratory involvement may require ventilatory support in the first or second decade of life.
Blepharospasm is a form of primary focal dystonia affecting the orbicularis oculi muscles, usually beginning in middle age. Initial symptoms include eye irritation and frequent blinking, progressing to involuntary spasms of eyelid closure. In severe cases, this can lead to functional blindness (summary by Misbahuddin et al., 2002).
Colorectal cancer is a heterogeneous disease that is common in both men and women. In addition to lifestyle and environmental risk factors, gene defects can contribute to an inherited predisposition to CRC. CRC is caused by changes in different molecular pathogenic pathways, such as chromosomal instability, CpG island methylator phenotype, and microsatellite instability. Chromosome instability is the most common alteration and is present in almost 85% of all cases (review by Schweiger et al., 2013). Genetic Heterogeneity of Colorectal Cancer Mutations in a single gene result in a marked predisposition to colorectal cancer in 2 distinct syndromes: familial adenomatous polyposis (FAP; 175100) and hereditary nonpolyposis colorectal cancer (HNPCC; see 120435). FAP is caused by mutations in the APC gene (611731), whereas HNPCC is caused by mutations in several genes, including MSH2 (609309), MLH1 (120436), PMS1 (600258), PMS2 (600259), MSH6 (600678), TGFBR2 (190182), and MLH3 (604395). Epigenetic silencing of MSH2 results in a form of HNPCC (see HNPCC8, 613244). Other colorectal cancer syndromes include autosomal recessive adenomatous polyposis (608456), which is caused by mutations in the MUTYH gene (604933), and oligodontia-colorectal cancer syndrome (608615), which is caused by mutations in the AXIN2 gene (604025). The CHEK2 gene (604373) has been implicated in susceptibility to colorectal cancer in Finnish patients. A germline mutation in the PLA2G2A gene (172411) was identified in a patient with colorectal cancer. Germline susceptibility loci for colorectal cancer have also been identified. CRCS1 (608812) is conferred by mutation in the GALNT12 gene (610290) on chromosome 9q22; CRCS2 (611469) maps to chromosome 8q24; CRCS3 (612229) is conferred by variation in the SMAD7 gene (602932) on chromosome 18; CRCS4 (601228) is conferred by variation on 15q that causes increased and ectopic expression of the GREM1 gene (603054); CRCS5 (612230) maps to chromosome 10p14; CRCS6 (612231) maps to chromosome 8q23; CRCS7 (612232) maps to chromosome 11q23; CRCS8 (612589) maps to chromosome 14q22; CRCS9 (612590) maps to 16q22; CRCS10 (612591) is conferred by mutation in the POLD1 gene (174761) on chromosome 19q13; CRCS11 (612592) maps to chromosome 20p12; and CRCS12 (615083) is conferred by mutation in the POLE gene (174762) on chromosome 12q24. Somatic mutations in many different genes, including KRAS (190070), PIK3CA (171834), BRAF (164757), CTNNB1 (116806), FGFR3 (134934), AXIN2 (604025), AKT1 (164730), MCC (159350), MYH11 (160745), PARK2 (602544), and RNF43 (612482), have been identified in colorectal cancer.
Cowden syndrome is a disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers.Almost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person's late twenties.Cowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus (the endometrium). Other cancers that have been identified in people with Cowden syndrome include colorectal cancer, kidney cancer, and a form of skin cancer called melanoma. Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. Additional signs and symptoms can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. A small percentage of affected individuals have delayed development or intellectual disability.The features of Cowden syndrome overlap with those of another disorder called Bannayan-Riley-Ruvalcaba syndrome. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors. Both conditions can be caused by mutations in the PTEN gene. Some people with Cowden syndrome have had relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other individuals have had the characteristic features of both conditions. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome instead of two distinct conditions.Some people have some of the characteristic features of Cowden syndrome, particularly the cancers associated with this condition, but do not meet the strict criteria for a diagnosis of Cowden syndrome. These individuals are often described as having Cowden-like syndrome.
Brown-Vialetto-Van Laere syndrome is a rare autosomal recessive neurologic disorder characterized by sensorineural hearing loss and a variety of cranial nerve palsies, usually involving the motor components of the seventh and ninth to twelfth (more rarely the third, fifth, and sixth) cranial nerves. Spinal motor nerves and, less commonly, upper motor neurons are sometimes affected, giving a picture resembling amyotrophic lateral sclerosis (ALS; 105400). The onset of the disease is usually in the second decade, but earlier and later onset have been reported. Hearing loss tends to precede the onset of neurologic signs, mostly progressive muscle weakness causing respiratory compromise. However, patients with very early onset may present with bulbar palsy and may not develop hearing loss until later. The symptoms, severity, and disease duration are variable (summary by Green et al., 2010). Genetic Heterogeneity of Brown-Vialetto-Van Laere Syndrome See also BVVLS2 (614707), caused by mutation in the SLC52A2 gene (607882) on chromosome 8q.
Familial progressive hyperpigmentation with or without hypopigmentation (FPHH) is characterized by diffuse hyperpigmentation of variable intensity sometimes associated with cafe-au-lait macules and larger hypopigmented ash-leaf macules. These features, which involve the face, neck, trunk, and limbs, are seen at birth or develop early in infancy (summary by Wang et al., 2009 and Amyere et al., 2011). Also see familial progressive hyperpigmentation (FPH1; 614233).
Adermatoglyphia is characterized by the lack of epidermal ridges on the palms and soles, which results in the absence of fingerprints, and is associated with a reduced number of sweat gland openings and reduced sweating of palms and soles (summary by Nousbeck et al., 2011). Basan syndrome (129200), a form of adermatoglyphia associated with congenital facial milia, acral blistering, digital contractures, and nail abnormalities, is also caused by mutation in SMARCAD1. Also see Naegeli-Franceschetti-Jadassohn syndrome (NFJS; 161000) and dermatopathia pigmentosa reticularis (DPR; 125595), 2 closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics and are caused by heterozygous nonsense or frameshift mutations in the KRT14 gene (148066).
The concept of mucosa-associated lymphoid tissue (MALT) lymphomas was introduced by Isaacson and Wright (1983). MALT lymphomas are now recognized as a distinct subtype of non-Hodgkin lymphoma (605027). B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas) are the most common form of lymphoma arising in extranodal sites, in most cases arising in the gastric mucosa (Isaacson and Spencer, 1995).
Mosaic variegated aneuploidy is an autosomal recessive disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies but is usually more than 25% and is substantially greater than in normal individuals. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor, and leukemia reported in several cases (summary by Hanks et al., 2004). Genetic Heterogeneity of Mosaic Variegated Aneuploidy Syndrome See also MVA2 (614114), caused by mutation in the CEP57 gene (607951) on chromosome 11q21, and MVA3 (617598), caused by mutation in the TRIP13 gene (604507) on chromosome 5p15.
Multiple sclerosis is a condition characterized by areas of damage (lesions) on the brain and spinal cord. These lesions are associated with destruction of the covering that protects nerves and promotes the efficient transmission of nerve impulses (the myelin sheath) and damage to nerve cells. Multiple sclerosis is considered an autoimmune disorder; autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs, in this case tissues of the nervous system.Multiple sclerosis usually begins in early adulthood, between ages 20 and 40. The symptoms vary widely, and affected individuals can experience one or more effects of nervous system damage. Multiple sclerosis often causes sensory disturbances in the limbs, including a prickling or tingling sensation (paresthesia), numbness, pain, and itching. Some people experience Lhermitte sign, which is an electrical shock-like sensation that runs down the back and into the limbs. This sensation usually occurs when the head is bent forward. Problems with muscle control are common in people with multiple sclerosis. Affected individuals may have tremors, muscle stiffness (spasticity), exaggerated reflexes (hyperreflexia), weakness or partial paralysis of the muscles of the limbs, difficulty walking, or poor bladder control. Multiple sclerosis is also associated with vision problems, such as blurred or double vision or partial or complete vision loss. Infections that cause fever can make the symptoms worse.There are several forms of multiple sclerosis: relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive relapsing MS. The most common is the relapsing-remitting form, which affects approximately 80 percent of people with multiple sclerosis. Individuals with this form of the condition have periods during which they experience symptoms, called clinical attacks, followed by periods without any symptoms (remission). The triggers of clinical attacks and remissions are unknown. After about 10 years, relapsing-remitting MS usually develops into another form of the disorder called secondary progressive MS. In this form, there are no remissions, and symptoms of the condition continually worsen.Primary progressive MS is the next most common form, affecting approximately 10 to 20 percent of people with multiple sclerosis. This form is characterized by constant symptoms that worsen over time, with no clinical attacks or remissions. Primary progressive MS typically begins later than the other forms, around age 40.Progressive relapsing MS is a rare form of multiple sclerosis that initially appears like primary progressive MS, with constant symptoms. However, people with progressive relapsing MS also experience clinical attacks of more severe symptoms.
Severe congenital neutropenia-3 is an autosomal recessive bone marrow failure disorder characterized by low numbers of neutrophils, increased susceptibility to bacterial and fungal infections, and increased risk of developing myelodysplastic syndrome or acute myeloid leukemia. In addition, patients with HAX1 mutations affecting both isoform A and B of the gene develop neurologic abnormalities (summary by Boztug et al., 2010). The Swedish physician Rolf Kostmann (1956) described an autosomal recessive hematologic disorder, termed infantile agranulocytosis, with severe neutropenia with an absolute neutrophil count below 0.5 x 10(9)/l and early onset of severe bacterial infections. The disorder was later termed Kostmann syndrome (Skokowa et al., 2007). Lekstrom-Himes and Gallin (2000) discussed severe congenital neutropenia in a review of immunodeficiencies caused by defects in phagocytes. In addition to Kostmann agranulocytosis, recessively inherited neutropenic syndromes include congenital neutropenia with eosinophilia (257100), Chediak-Higashi syndrome (214500), and Fanconi pancytopenic syndrome (see 227650). For a phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700).
Prothrombin-related thrombophilia is characterized by venous thromboembolism (VTE) manifest most commonly in adults as deep-vein thrombosis (DVT) in the legs or pulmonary embolism. The clinical expression of prothrombin-related thrombophilia is variable; many individuals heterozygous or homozygous for the 20210G>A (G20210A or c.*97G>A) allele in F2 never develop thrombosis, and while most heterozygotes who develop thrombotic complications remain asymptomatic until adulthood, some have recurrent thromboembolism before age 30 years. The relative risk for DVT in adults heterozygous for the 20210G>A allele is two- to fivefold increased; in children, the relative risk for thrombosis is three- to fourfold increased. 20210G>A heterozygosity has at most a modest effect on recurrence risk after a first episode. Although prothrombin-related thrombophilia may increase the risk for pregnancy loss, its association with preeclampsia and other complications of pregnancy such as intrauterine growth restriction and placental abruption remains controversial. Factors that predispose to thrombosis in prothrombin-related thrombophilia include: the number of 20210G>A alleles; presence of coexisting genetic abnormalities including factor V Leiden; and acquired thrombophilic disorders (e.g., antiphospholipid antibodies). Circumstantial risk factors for thrombosis include pregnancy and oral contraceptive use. Some evidence suggests that the risk for VTE in 20210G>A heterozygotes increases after travel.
Pontocerebellar hypoplasia (PCH) refers to a group of severe neurodegenerative disorders affecting growth and function of the brainstem and cerebellum, resulting in little or no development. Different types were classified based on the clinical picture and the spectrum of pathologic changes. PCH type 1 is characterized by central and peripheral motor dysfunction associated with anterior horn cell degeneration resembling infantile spinal muscular atrophy (SMA; see SMA1, 253300); death usually occurs early. Genetic Heterogeneity of Pontocerebellar Hypoplasia Also see PCH1B (614678), caused by mutation in the EXOSC3 gene (606489); PCH1C (616081), caused by mutation in the EXOSC8 gene (606019); PCH1D (618065), caused by mutation in the EXOSC9 gene (606180); PCH2A (277470), caused by mutation in the TSEN54 gene (608755); PCH2B (612389), caused by mutation in the TSEN2 gene (608753); PCH2C (612390), caused by mutation in the TSEN34 gene (608754); PCH2D (613811), caused by mutation in the SEPSECS gene (613009); PCH3 (608027), caused by mutation in the PCLO gene (604918); PCH4 (225753), caused by mutation in the TSEN54 gene; PCH5 (610204), caused by mutation in the TSEN54 gene; PCH6 (611523), caused by mutation in the RARS2 gene (611524); PCH7 (614969), caused by mutation in the TOE1 gene (613931); PCH8 (614961), caused by mutation in the CHMP1A gene (164010); PCH9 (615809), caused by mutation in the AMPD2 gene (102771); PCH10 (615803), caused by mutation in the CLP1 gene (608757); PCH11 (617695), caused by mutation in the TBC1D23 gene (617687); and PCH12 (618266), caused by mutation in the COASY gene (609855).
Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype) (Gribouval et al., 2005). Absence or paucity of differentiated proximal tubules is the histopathologic hallmark of the disorder and may be associated with skull ossification defects.
Human personality is shaped by genetic and environmental factors, and evidence suggests that the genetic component is highly complex, polygenic, and epistatic. Genetic factors are thought to contribute to 40 to 60% of trait variance. Molecular genetics has tried to identify specific genes for quantitative traits, called quantitative trait loci (QTLs). The QTL concept suggests that complex personality traits or dimensions are not attributable to single genes, but to multiple interacting genes (Reif and Lesch, 2003). Fullerton et al. (2003) stated that psychologists were in agreement that the wide variation in human personalities can be explained by a small number of personality factors, including neuroticism (a measure of emotional stability), which manifests at one extreme as anxiety, depression, moodiness, low self-esteem, and diffidence. They cited a number of studies that had described a relationship between high scores on measures of neuroticism and major depressive disorder. They also noted that theoretical studies had suggested that large samples of randomly ascertained sibs could be used to ascertain phenotypically extreme individuals and thereby increase power to detect genetic linkage in complex traits. See also panic disorder (PAND1; 167870), which is a subtype of anxiety disorder.
Congnital aplastic deformities of the breast include amastia (total absence of breasts and nipple), athelia (absence of the nipple), and amazia (absence of the mammary gland). Most common is amastia. Bilateral absence of the breasts may occur as an isolated anomaly or may be associated with a syndrome or a cluster of other anomalies, including anhidrotic ectodermal dysplasia (305100) and Poland syndrome (173800) (summary by Papadimitriou et al., 2009). Genetic Heterogeneity of Aplasia or Hypoplasia of Breasts and/or Nipples An autosomal recessive form of breast and/or nipple aplasia or hypoplasia (BNAH2; 616001) is caused by mutation in the PTPRF gene (179590) on chromosome 1p34.
Congenital diaphragmatic hernia (CDH) is characterized by: (1) incomplete formation/muscularization of the diaphragm resulting in absence or deficiency of the diaphragm, or (2) eventration resulting in elevation of a portion of the diaphragm that is thinned as a result of incomplete muscularization. Diaphragmatic hernias include posterolateral (Bochdalek) hernias, Morgagni and other anterior hernias, and (rarely) central hernias. About 50%-60% of affected individuals have isolated CDH; the remainder have complex CDH – that is, CDH occurring with additional malformations or as part of a single-gene disorder or chromosome abnormality. Infants with CDH often present in the neonatal period with severe respiratory distress; pulmonary hypoplasia is common. Presenting symptoms after infancy can be acute onset of respiratory or gastrointestinal distress or abdominal pain from chronic intestinal obstruction or pleural effusion from entrapment of the bowel in the chest.
Focal dystonia, the most common form of dystonia, is often task-specific and referred to as FTSD. Specific learned motor tasks, such as writing or playing a musical instrument, can trigger muscle spasms and interfere with performance while other actions are unaffected. FTSD has a frequency of 1 in 3,400 in the general population but increases to 1 in 200 among musicians (Pullman and Hristova, 2005).
Hemolytic anemia following ingestion of the bean of Vicia faba or exposure to its pollen is conditioned primarily by a deficiency of erythrocyte glucose-6-phosphate dehydrogenase, an X-linked genetic trait (300908). In areas where the enzyme deficiency is frequent, favism shows familial aggregation probably not accounted for by the familial occurrence of the enzyme deficiency alone (Stamatoyannopoulos et al., 1966).
Steroid-resistant nephrotic syndrome type 2 is an autosomal recessive disorder characterized clinically by childhood onset of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. The disorder is resistant to steroid treatment and progresses to end-stage renal failure in the first or second decades (summary by Fuchshuber et al., 1996). Some patients show later onset of the disorder (Tsukaguchi et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of nephrotic syndrome and FSGS, see NPHS1 (256300).
Esophageal atresia/tracheoesophageal fistula (EA/TEF) is a condition resulting from abnormal development before birth of the tube that carries food from the mouth to the stomach (the esophagus). During early development, the esophagus and windpipe (trachea) begin as a single tube that normally divides into the two adjacent passages between four and eight weeks after conception. If this separation does not occur properly, EA/TEF is the result.In esophageal atresia (EA), the upper esophagus does not connect (atresia) to the lower esophagus and stomach. Almost 90 percent of babies born with esophageal atresia also have a tracheoesophageal fistula (TEF), in which the esophagus and the trachea are abnormally connected, allowing fluids from the esophagus to get into the airways and interfere with breathing. A small number of infants have only one of these abnormalities.There are several types of EA/TEF, classified by the location of the malformation and the structures that are affected. In more than 80 percent of cases, the lower section of the malformed esophagus is connected to the trachea (EA with a distal TEF). Other possible configurations include having the upper section of the malformed esophagus connected to the trachea (EA with a proximal TEF), connections to the trachea from both the upper and lower sections of the malformed esophagus (EA with proximal and distal TEF), an esophagus that is malformed but does not connect to the trachea (isolated EA), and a connection to the trachea from an otherwise normal esophagus (H-type TEF with no EA).While EA/TEF arises during fetal development, it generally becomes apparent shortly after birth. Saliva, liquids fed to the infant, or digestive fluids may enter the windpipe through the tracheoesophageal fistula, leading to coughing, respiratory distress, and a bluish appearance of the skin or lips (cyanosis). Esophageal atresia blocks liquids fed to the infant from entering the stomach, so they are spit back up, sometimes along with fluids from the respiratory tract. EA/TEF is a life-threatening condition; affected babies generally require surgery to correct the malformation in order to allow feeding and prevent lung damage from repeated exposure to esophageal fluids.EA/TEF occurs alone (isolated EA/TEF) in about 40 percent of affected individuals. In other cases it occurs with other birth defects or as part of a genetic syndrome (non-isolated or syndromic EA/TEF).
The mitochondrial trifunctional protein, composed of 4 alpha and 4 beta subunits, catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids: long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), long-chain enoyl-CoA hydratase, and long-chain thiolase activities. Trifunctional protein deficiency is characterized by decreased activity of all 3 enzymes. Clinically, classic trifunctional protein deficiency can be classified into 3 main clinical phenotypes: neonatal onset of a severe, lethal condition resulting in sudden unexplained infant death (SIDS; 272120), infantile onset of a hepatic Reye-like syndrome, and late-adolescent onset of primarily a skeletal myopathy (Spiekerkoetter et al., 2003). Some patients with MTP deficiency show a protracted progressive course associated with myopathy, recurrent rhabdomyolysis, and sensorimotor axonal neuropathy. These patients tend to survive into adolescence and adulthood (den Boer et al., 2003). See also isolated LCHAD deficiency (609016), which is caused by mutation in the HADHA gene.
Androgen insensitivity syndrome is a condition that affects sexual development before birth and during puberty. People with this condition are genetically male, with one X chromosome and one Y chromosome in each cell. Because their bodies are unable to respond to certain male sex hormones (called androgens), they may have mostly female external sex characteristics or signs of both male and female sexual development.Complete androgen insensitivity syndrome occurs when the body cannot use androgens at all. People with this form of the condition have the external sex characteristics of females, but do not have a uterus and therefore do not menstruate and are unable to conceive a child (infertile). They are typically raised as females and have a female gender identity. Affected individuals have male internal sex organs (testes) that are undescended, which means they are abnormally located in the pelvis or abdomen. Undescended testes have a small chance of becoming cancerous later in life if they are not surgically removed. People with complete androgen insensitivity syndrome also have sparse or absent hair in the pubic area and under the arms.The partial and mild forms of androgen insensitivity syndrome result when the body's tissues are partially sensitive to the effects of androgens. People with partial androgen insensitivity (also called Reifenstein syndrome) can have genitalia that look typically female, genitalia that have both male and female characteristics, or genitalia that look typically male. They may be raised as males or as females and may have a male or a female gender identity. People with mild androgen insensitivity are born with male sex characteristics, but they are often infertile and tend to experience breast enlargement at puberty.
The disorder dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease is characterized by the following: A movement disorder resulting from manganese accumulation in the basal ganglia. Whole-blood manganese concentrations that often exceed 2000 nmol/L (normal: <320 nmol/L). Polycythemia. Hepatomegaly with variable hepatic fibrosis/cirrhosis. Neurologic findings can manifest: in childhood (ages 2-15 years) as four-limb dystonia, leading to a characteristic high-stepping gait (""cock-walk gait""), dysarthria, fine tremor, and bradykinesia or on occasion spastic paraplegia; or in adulthood as parkinsonism (shuffling gait, rigidity, bradykinesia, hypomimia, and monotone speech) unresponsive to L-dopa treatment. Hepatic failure, secondary complications of cirrhosis, and the neurologic disorder shorten life expectancy.
Crohn disease is a complex, long-lasting (chronic) disorder that primarily affects the digestive system. This condition involves an abnormal immune response that causes excess inflammation. It most often affects the intestinal walls, particularly in the lower part of the small intestine (the ileum) and portions of the large intestine (the colon). However, inflammation can occur in any part of the digestive system, from the mouth to the anus. The inflamed tissues become thick and swollen, and the inner surfaces of the digestive system may develop open sores (ulcers).Crohn disease most commonly appears in a person's late teens or twenties, although the disease can begin at any age. Signs and symptoms tend to flare up multiple times throughout life. The most common features of this condition are persistent diarrhea, abdominal pain and cramping, loss of appetite, weight loss, and fever. Some people with Crohn disease have blood in the stool from inflamed tissues in the intestine; over time, chronic bleeding can lead to a low number of red blood cells (anemia). In some cases, Crohn disease can also cause inflammation affecting the joints, eyes, or skin.Intestinal blockage is a common complication of Crohn disease. Blockages are caused by swelling or a buildup of scar tissue in the intestinal walls. Some affected individuals also develop fistulae, which are abnormal connections between the intestine and other tissues. Fistulae occur when ulcers break through the intestinal wall and passages form between loops of the intestine or between the intestine and nearby structures (such as the bladder, vagina, or skin).Crohn disease is one common form of inflammatory bowel disease (IBD). Another type of IBD, ulcerative colitis, also causes chronic inflammation of the intestinal lining. Unlike Crohn disease, which can affect any part of the digestive system, ulcerative colitis typically causes inflammation only in the colon.
The phenotypes of dihydrolipoamide dehydrogenase (DLD) deficiency are an overlapping continuum that ranges from early-onset neurologic manifestations to adult-onset isolated liver involvement. Early-onset DLD deficiency typically manifests as a hypotonic infant with lactic acidosis. Affected infants frequently do not survive their initial metabolic decompensation, or die within the first few years of life during a recurrent metabolic decompensation. Children who live beyond the first two to three years frequently exhibit growth deficiencies and residual neurologic deficits (intellectual disability, spasticity, ataxia, and seizures). In contrast, isolated liver involvement can present as early as the neonatal period and as late as the third decade. Evidence of liver injury/failure is preceded by nausea and emesis and frequently associated with encephalopathy and/or coagulopathy. Acute metabolic episodes are frequently associated with lactate elevations, hyperammonemia, and hepatomegaly. With resolution of the acute episodes patients frequently return to baseline with no residual neurologic deficit or intellectual disability. Liver failure can result in death, even in those with late-onset disease.
Color vision deficiency (sometimes called color blindness) represents a group of conditions that affect the perception of color. Red-green color vision defects are the most common form of color vision deficiency. Affected individuals have trouble distinguishing between some shades of red, yellow, and green. Blue-yellow color vision defects (also called tritan defects), which are rarer, cause problems with differentiating shades of blue and green and cause difficulty distinguishing dark blue from black. These two forms of color vision deficiency disrupt color perception but do not affect the sharpness of vision (visual acuity).A less common and more severe form of color vision deficiency called blue cone monochromacy causes very poor visual acuity and severely reduced color vision. Affected individuals have additional vision problems, which can include increased sensitivity to light (photophobia), involuntary back-and-forth eye movements (nystagmus), and nearsightedness (myopia). Blue cone monochromacy is sometimes considered to be a form of achromatopsia, a disorder characterized by a partial or total lack of color vision with other vision problems.
Deficiency of plasma platelet-activating factor acetylhydrolase results in increased levels of PAF, a chemotactic lipid that activates inflammatory cells, bronchoconstriction, and airway hyperresponsiveness, and can moderate the release of inflammatory agonists. Asthmatic individuals with PAF acetylhydrolase deficiency may have exacerbated symptoms (summary by Stafforini et al., 1999).
Phenytoin, a widely used antiepileptic drug, has a narrow therapeutic index and large inter-patient variability, partly due to CYP2C9 genetic variation. Patients with the CYP2C9 poor metabolizer phenotype may require reduced doses of phenytoin. Additionally, the HLA-B*15:02 variant is associated with an increased risk of phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Patients who carry at least one copy of the HLA-B*15:02 allele (considered HLA-B*15:02-positive) have a significantly increased risk for SJS/TEN compared to non-carriers, and it is recommended that they receive an alternate drug. It is important to note that it is possible for a patient without HLA-B*15:02 to develop SJS/TEN. Therapeutic guidelines for phenytoin based on CYP2C9 and HLA-B genotypes have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
NMAN is an autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 (see, e.g., CMT2A1, 118210) and distal hereditary motor neuropathy (see, e.g., HMN1, 182960). Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves (summary by Zimon et al., 2012).
Hereditary motor and sensory neuropathies (HMSN) are a heterogeneous group of peripheral nervous system disorders affecting motor and sensory function. HMSN I, also known as Charcot-Marie-Tooth (CMT) disease, or peroneal muscular atrophy, type 1, is a demyelinating neuropathy (see CMT1B; 118200) and HMSN II, also known as CMT type 2, is an axonal neuropathy (see CMT2A1; 118210). See also HMSN III (145900) and HMSN IV (266500). For an autosomal recessive disorder with similarities to HMSN V, see 607731.
CMO type I deficiency is an autosomal recessive disorder caused by a defect in the penultimate biochemical step of aldosterone biosynthesis, the 18-hydroxylation of corticosterone (B) to 18-hydroxycorticosterone (18-OHB). This enzymatic defect results in decreased aldosterone and salt-wasting. In CMO I deficiency, aldosterone is undetectable, whereas its immediate precursor, 18-OHB, is low or normal. These patients have an increased ratio of corticosterone to 18-OHB (Portrat-Doyen et al., 1998). The CYP11B2 gene product also catalyzes the final step in aldosterone biosynthesis: the 18-oxidation of 18-OHB to aldosterone. A defect in that enzymatic step results in CMO type II deficiency (610600), an allelic disorder with an overlapping phenotype but distinct biochemical features. In CMO II deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18-OHB. These patients have a low ratio of corticosterone to 18-OHB (Portrat-Doyen et al., 1998).
Aripiprazole is an atypical antipsychotic used in the management of schizophrenia, bipolar disorder, major depressive disorder, irritability associated with autistic disorder, and treatment of Tourette’s disorder. The metabolism and elimination of aripiprazole is mainly mediated through two enzymes, CYP2D6 and CYP3A4. Approximately 8% of Caucasians, 3–8% of Black/African Americans and up to 2% of Asians cannot metabolize CYP2D6 substrates and are classified as “poor metabolizers”. The FDA-approved drug label for aripiprazole states that in CYP2D6 poor metabolizers, half of the usual dose should be administered. In CYP2D6 poor metabolizers who are taking concomitant strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin), a quarter of the usual dose should be used.
Atomoxetine was the first non-stimulant drug to be used in the treatment of attention-deficit hyperactivity disorder (ADHD). Atomoxetine is a selective noradrenaline reuptake inhibitor, and is part of a treatment plan for ADHD that may include other measures such as psychological, educational, and social support. The CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, including atomoxetine. Individuals who carry two nonfunctional copies of the CYP2D6 gene are known as poor metabolizers and have higher plasma concentrations of atomoxetine compared with individuals who have two copies of normal activity alleles. The FDA states that the dose of atomoxetine may need to be adjusted in patients known to be CYP2D6 poor metabolizers. A guideline from The Dutch Pharmacogenetics Working Group includes the recommendation that poor metabolizers can be given the standard dose of atomoxetine, but physicians should be aware of adverse drug events. They also state that for individuals who have more than two functional gene copies of CYP2D6, i.e., individuals with so-called ultrarapid metabolizer status, physicians should either be alert to reduced efficacy with the standard dose of atomoxetine, or they should prescribe an alternative drug, such as methylphenidate or clonidine.
Voriconazole is a triazole antifungal agent active against a variety of fungi and molds. While it is generally well-tolerated and effective, it has a narrow therapeutic window making it difficult to dose correctly. CYP2C19 is the primary enzyme responsible for the metabolism of the drug, and variations within the CYP2C19 gene may affect voriconazole exposure. CYP2C19 ultrarapid and rapid metabolizers may have increased metabolism of the drug, resulting in a reduced likelihood of attaining therapeutic voriconazole concentrations, while poor metabolizers may have decreased metabolism of the drug, resulting in an increased likelihood for adverse effects. Therapeutic guidelines for voriconazole based on CYP2C19 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (https://www.pharmgkb.org/guideline/PA166161537).
PEG-interferon alpha (PEG-IFN 2a and 2b, or PEG-IFN alpha), in combination with ribavirin, is used to treat Hepatitis C Virus (HCV) infection. IFNL3 (also known as IL28B) is a member of the type 3 IFN-alpha family, which are induced by viruses and inhibit HCV replication in vitro. Genetic variants in IFNL3 are associated with increased response (higher sustained virological response rate) to PEG-interferon alpha/ribavirin combination therapy and clearance of HCV. In 2011, the protease inhibitors boceprevir and telaprevir were approved to treat HCV genotype 1 infection in many countries, including the United States and those in the European Union, and are now included in HCV combination therapy. IFNL3 genotype predicts response to this combination therapy and also predicts eligibility for shorter duration of therapy. Guidelines regarding the clinical use of PEG-interferon alpha containing regimens based on IFNL3 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA164749390).
Capecitabine is a chemotherapeutic agent and a member of the fluoropyrimidine group of substances. It is a prodrug of 5-fluorouracil and mainly used to treat solid tumors, such as colorectal, breast and aerodigestive cancers. Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) is the rate-limiting enzyme for fluoropyrimidine metabolism and is therefore responsible for the detoxification of these types of drugs. Patients who are homozygous for variants in DPYD that lead to a non-functional protein, such as *2A or *13, have a high risk of severe or fatal drug toxicities and may benefit from receiving an alternative chemotherapeutic drug. Patients heterozygous for these variants also have an increased risk for drug toxicities, and reduced dosing is recommended for these individuals. Guidelines regarding the use of pharmacogenomic tests in dosing for capecitabine have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA448771).
Carvedilol (brand name Coreg) is used to treat heart failure and high blood pressure (hypertension). It is also used in patients who developed left ventricular dysfunction after having a heart attack (myocardial infarction, MI). In patients with cardiovascular disease, carvedilol is associated with improvements in quality of life, hospitalization rates, and survival. Carvedilol is a non-selective beta blocker (beta 1 and beta 2) and an alpha 1 blocker. It reduces the energy demands on the heart by blocking cardiac beta receptors, which decreases the heart rate and the force of heart contractions. Carvedilol lowers blood pressure by blocking alpha receptors on blood vessels, which relaxes and dilates blood vessels. CYP2D6 is one of the primary enzymes involved in activating and metabolizing carvedilol. Approximately 8% of Caucasians and 2% of most other populations have absent CYP2D6 activity and are predicted to be “CYP2D6 poor metabolizers.” The FDA-approved drug label for carvedilol states that plasma concentrations of carvedilol may be higher in CYP2D6 poor metabolizers compared to normal metabolizers, but does not discuss altering carvedilol dosing based on a patient’s CYP2D6 genotype. However, the label does state the dose of carvedilol should be individualized, and the dose should be monitored as it is gradually increased (up-titrated), based on tolerability and clinical response. The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) recommend that no action is needed for carvedilol and CYP2D6 genotype. For CYP2D6 poor metabolizers, DPWG states that the plasma concentration of carvedilol can be elevated, but this does not result in an increase in side effects.
Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that is used in the management of osteoarthritis, rheumatoid arthritis, menstrual symptoms, and acute pain. Most NSAIDs inhibit both types of cyclooxygenase, COX-1 and COX-2. These enzymes catalyze pathways that play a key role in the generation of the inflammatory response; however, celecoxib, selectively inhibits COX-2. The CYP2C9 gene encodes an enzyme involved in the metabolism of many drugs, and is one of the main enzymes that metabolizes and inactivates celecoxib. Two common variants, CYP2C9*2 and CYP2C9*3, are associated with significantly reduced CYP2C9 enzyme activity. Individuals who carry two copies of these variants (or other loss-of-function variant CYP2C9 alleles) are considered CYP2C9 ""poor metabolizers"" and may be exposed to high drug levels after standard celecoxib doses. The FDA-approved drug label for celecoxib states: “patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin, phenytoin) should be administered celecoxib with caution. Consider starting treatment at half the lowest recommended dose in poor metabolizers (i.e., CYP2C9*3/*3). Consider using alternative management in juvenile rheumatoid arthritis (JRA) patients who are poor metabolizers”.
Clozapine is one of the most effective antipsychotics available in the treatment of schizophrenia and the only antipsychotic found to be effective in treatment-resistant schizophrenia. Clozapine is also used to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Compared to typical antipsychotics, clozapine is far less likely to cause movement disorders, known as extrapyramidal side effects, which include dystonia, akathisia, parkinsonism, and tardive dyskinesia. However, there are significant risks associated with clozapine therapy that limits its use to only the most severely ill patients who have not responded adequately to standard drug therapy. Most notably, because of the risk of clozapine-induced agranulocytosis, clozapine treatment requires monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA requires that patients receiving clozapine be enrolled in a computer-based registry. Clozapine is metabolized in the liver by the cytochrome P450 (CYP) system of enzymes. CYP1A2 is the main CYP isoform in clozapine metabolism and CYP1A2 activity is an important determinant of clozapine dose. Other CYP enzymes involved in clozapine metabolism include CYP2D6 and CYP3A4. Approximately 6-10% of Caucasians have reduced activity of CYP2D6 (poor metabolizers). These individuals may develop higher than expected plasma concentrations of clozapine with usual doses. The FDA-approved drug label for clozapine states that a dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.
Diazepam is a benzodiazepine with several clinical uses, including the management of anxiety, insomnia, muscle spasms, seizures, and alcohol withdrawal. The clinical response to benzodiazepines, such as diazepam, varies widely between individuals. Diazepam is primarily metabolized by CY2C19 and CYP3A4 to the major active metabolite, desmethyldiazepam. Approximately 3% of Caucasians and 15 to 20% of Asians have reduced or absent CYP2C19 enzyme activity (“poor metabolizers”). In these individuals, standard doses of diazepam may lead to a higher exposure to diazepam. The FDA-approved drug label for diazepam states that “The marked inter-individual variability in the clearance of diazepam reported in the literature is probably attributable to variability of CYP2C19 (which is known to exhibit genetic polymorphism; about 3-5% of Caucasians have little or no activity and are “poor metabolizers”) and CYP3A4”.
Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by CYP2C19 to pharmacologically active metabolites. These drugs and their metabolites, along with desipramine and nortriptyline, undergo hydroxylation by CYP2D6 to less active metabolites. Evidence from published literature is presented for CYP2D6 and CYP2C19 genotype–directed dosing of tricyclic antidepressants.
Esomeprazole blocks the secretion of gastric acid and belongs to the drug class of proton pump inhibitors. It is used to treat gastroesophageal reflux disease (GERD) and to reduce the risk of gastric ulcers associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Esomeprazole is also used in the treatment of hypersecretory conditions, such as Zollinger-Ellison syndrome, and is used in combination with antibiotics to eradicate Helicobacter pylori (H. pylori) infection. Esomeprazole is metabolized primarily by the CYP2C19 enzyme. Approximately 3% of Caucasians and 15 to 20% of Asians have reduced or absent CYP2C19 enzyme activity (""poor metabolizers""). In these individuals, standard doses of esomeprazole leads to higher exposure of the drug. In contrast, individuals with increased CYP2C19 activity (""ultrarapid metabolizers"") may be exposed to lower levels of esomeprazole and have an insufficient response to treatment. The FDA-approved drug label for esomeprazole states that poor metabolizers are exposed to approximately twice the level of drug compared to the rest of the population (""extensive metabolizers""), but the label does not require dose changes for poor metabolizers. However, the Pharmacogenetics Working Group of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) has published dose alterations based on CYP2C19 genotype. For CYP2C19 poor metabolizers, they do not recommend altering the dose; however for ultrarapid metabolizers, they recommend being extra alert to an insufficient response to treatment. For the eradication of H. pylori in ultrarapid metabolizers, KNMP recommends increasing the dose of omeprazole by 50–100%, and to consider the same dose increase for other conditions.
5-fluorouracil is a chemotherapeutic agent, and a member of the fluoropyrimidine group of substances. It is mainly used to treat solid tumors, such as colorectal, breast and aerodigestive cancers. Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) is the rate-limiting enzyme for fluoropyrimidine metabolism and is therefore responsible for the detoxification of these types of drugs. Patients who are homozygous for variants in DPYD that lead to a non-functional protein, such as *2A or *13, have a high risk of severe or fatal drug toxicities and may benefit from receiving an alternative chemotherapeutic drug. Patients heterozygous for these variants also have an increased risk for drug toxicities, and reduced dosing is recommended for these individuals. Guidelines regarding the use of pharmacogenomic tests in dosing for 5-fluorouracil have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA128406956).
Irinotecan (brand name Camptosar) is a topoisomerase I inhibitor widely used in the treatment of cancer. It is most frequently used in combination with other drugs to treat advanced or metastatic colorectal cancer. However, irinotecan therapy is associated with a high incidence of toxicity, including severe neutropenia and diarrhea. Irinotecan is converted in the body to an active metabolite known as SN-38, which is then inactivated and detoxified by a UDP-glucuronosyltransferase (UGT) enzyme encoded by the UGT1A1 gene. The UGT enzymes are responsible for glucuronidation, a process that transforms lipophilic metabolites into water-soluble metabolites that can be excreted from the body. The risk of irinotecan toxicity increases with genetic variants associated with reduced UGT enzyme activity, such as UGT1A1*28. The presence of this variant results in reduced excretion of irinotecan metabolites, which leads to increased active irinotecan metabolites in the blood. Approximately 10% of North Americans carry 2 copies of the UGT1A1*28 allele (homozygous, UGT1A1 *28/*28), and are more likely to develop neutropenia following irinotecan therapy. The FDA-approved drug label for irinotecan states that “when administered as a single-agent, a reduction in the starting dose by at least one level of irinotecan hydrochloride injection should be considered for patients known to be homozygous for the UGT1A1*28 allele. However, the precise dose reduction in this patient population is not known and subsequent dose modifications should be considered based on individual patient tolerance to treatment”. The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) recommends starting with 70% of the standard dose for homozygous carriers of the UGT1A1*28 allele. If the patient tolerates this initial dose, the dose can be increased guided by the neutrophil count. They state that no action is needed for heterozygous carriers of the UGT1A1*28 allele (e.g., UGT1A1 *1/*28). In addition, the French National Network of Pharmacogenetics (RNPGx) has proposed a decision tree for guiding irinotecan prescribing based on the UGT1A1 genotype and irinotecan dose.
Maraviroc is a chemokine receptor antagonist that is used in combination with other antiretroviral agents to treat human immunodeficiency virus type 1 (HIV-1) infection. Maraviroc exerts its therapeutic activity by blocking entry of the HIV-1 virus into immune cells—specifically the CD4-expressing T-helper cells, which play a major role in protecting the body from infection—precursor cells, and dendritic cells. HIV-1 infection is classified in two major forms according to the co-receptor it employs to gain entry in to the cell, namely the chemokine receptor 5 (CCR5) or the CXC chemokine receptor 4 (CXCR4). These co-receptors are expressed on different types of cells, and HIV tropism refers to the types of cells and tissues in which the virus infects and replicates. A tropism assay is conducted to determine which co-receptor the HIV-1 virus uses, i.e., whether the virus is CCR5-tropic, CXCR4-tropic, dual tropic (i.e., HIV-1 virus that is able to use both receptors), or mixed tropic (i.e., a mixture of HIV-1 viruses, some of which use CCR5 and others that use CXCR4). Maraviroc is only indicated for treatment of adults with CCR5 tropic HIV-1 and is not recommended when the CXCR4-tropic virus has been detected. The FDA-approved drug label for maraviroc states that “prior to initiation of maraviroc, test all patients for CCR5 tropism using a highly sensitive tropism assay”.
Metoprolol is a beta blocker used in the treatment of hypertension, angina, and heart failure. Metoprolol selectively blocks beta1 adrenoreceptors mainly expressed in cardiac tissue. Blockade of these receptors reduces the heart rate and decreases the force of heart contractions. Metoprolol is primarily metabolized by the CYP2D6 enzyme. Approximately 8% of Caucasians and 2% of most other populations have absent CYP2D6 activity and are known as “CYP2D6 poor metabolizers.” In addition, a number of drugs inhibit CYP2D6 activity, such as quinidine, fluoxetine, paroxetine, and propafenone. The FDA-approved drug label for metoprolol states that CYP2D6 poor metabolizers, and normal metabolizers who concomitantly take drugs that inhibit CYP2D6, will have increased (several-fold) metoprolol blood levels, decreasing metoprolol’s cardioselectivity. The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) has published metoprolol dosing recommendations based on CYP2D6 genotype. For individuals who have a CYP2D6 gene variation that reduces the conversion of metoprolol to inactive metabolites, DPWG states that the clinical consequences are limited mainly to the occurrence of asymptomatic bradycardia. For CYP2D6 poor metabolizers, if a gradual reduction in heart rate is desired, or in the event of symptomatic bradycardia, DPWG recommends increasing the dose of metoprolol in smaller steps and/or prescribing no more than 25% of the standard dose. For other cases, no action is required. Please note: Beta blockers such as metoprolol have been demonstrated in several large trials to be safe and effective for treatment of patients with cardiovascular disease. As a mainstay of therapy associated with improvements in quality of life, hospitalization rates, and survival, clinical care pathways that might lead to underutilization of beta blockers require scrutiny. FDA points out that CYP2D6 poor metabolizers will have decreased cardioselectivity for metoprolol due to increased metoprolol blood levels. Yet, it is common clinical practice to adjust the dose of metoprolol according to the patient’s heart rate. FDA does not specifically comment on the role of genetic testing for initiating therapy.
Propafenone is an antiarrhythmic medication. It is used to prevent the reoccurrence of atrial fibrillation in patients with episodic atrial fibrillation who do not have underlying structural heart disease (propafenone may provoke proarrhythmic events in patients with structural heart disease). Propafenone belongs to class IC of antiarrhythmic agents and acts on cardiac sodium channels to inhibit action potentials. In general, because of the lack of evidence that antiarrhythmic agents improve survival, they should only be used to treat arrhythmias that are thought to be life-threatening. Propafenone is metabolized by CYP2D6, CYP3A4, and CYP1A2 enzymes. Approximately 6% of Caucasians in the US lack CYP2D6 activity, and are known as “CYP2D6 poor metabolizers”. Standard doses of propafenone will lead to higher plasma drug concentrations in poor metabolizers, compared to normal metabolizers. In addition, drugs that inhibit CYP2D6, CYP3A4, and CYP1A2 may also increase propafenone levels, which may lead to cardiac arrhythmia episodes. The FDA-approved drug label for propafenone states that the recommended dosing regimen of propafenone is the same for all patients (CYP2D6 poor metabolizers and normal metabolizers). However, the label also cautions that the simultaneous use of propafenone with both a CYP2D6 inhibitor (or in patients with CYP2D6 deficiency) and a CYP3A4 inhibitor should be avoided, because of the increased risk of causing arrhythmias and other adverse events. A guideline from The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Pharmacists Association (KNMP) provides dosing recommendations for propafenone, based on CYP2D6 genotype. For CYP2D6 poor metabolizers, the guideline recommends reducing the initial dose of propafenone by 70%, ECG monitoring, and monitoring plasma concentrations. For intermediate and ultrarapid metabolizers, the guideline states there is insufficient data to allow for a calculation of dose adjustment. Therefore, it is recommended to adjust the dose in response to plasma concentration and to monitor with ECG, or select an alternative drug (e.g., sotalol, disopyramide, quinidine, amiodarone).
Rasburicase is a drug that lowers uric acid levels and is used to treat or prevent hyperuricemia. It is contraindicated in patients with G6PD deficiency, a condition resulting from variants within the G6PD gene, which increases susceptibility to hemolytic anemia. Although the presence of known G6PD genetic variants may be able to be used to establish a diagnosis of G6PD deficiency, in most cases, a red blood cell G6PD enzyme activity assay remains required to assign G6PD status. Therapeutic guidelines for rasburicase based on G6PD genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Risperidone is the most commonly prescribed antipsychotic medication in the US. It is an atypical (second generation) antipsychotic used in the treatment of schizophrenia, bipolar disorder, severe dementia, and irritability associated with autism. Risperidone is metabolized to the active metabolite 9-hydroxyrisperidone by the enzyme CYP2D6 and to a lesser extent by CYP3A4. Individuals who carry two inactive copies of the CYP2D6 gene are termed “poor metabolizers” and may have a decreased capacity to metabolize risperidone. These individuals may be at a higher risk of adverse effects because of increased exposure to plasma risperidone, compared to normal metabolizers, who carry two active copies of CYP2D6. Individuals who are CYP2D6 ultrarapid metabolizers (who carry more than two functional copies of CYP2D6) may have a decreased response to therapy, resulting from lower steady-state risperidone concentrations. The FDA-approved drug label states that analysis of clinical studies involving a modest number of poor metabolizers (n=70) does not suggest that poor and extensive (normal) metabolizers have different rates of adverse effects. In addition, the Dutch Pharmacogenetics Working Group (DPWG) recently changed its dosing recommendations to “no action is needed” for CYP2D6 poor metabolizers taking risperidone.
Tamoxifen is a selective estrogen receptor modulator (SERM) which is used in the treatment and prevention of breast cancer . The CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, and is one of the main enzymes responsible for converting tamoxifen into its major active metabolite, endofixen. Variants in the CYP2D6 allele may lead to reduced (“intermediate metabolizer”) or absent (“poor metabolizer”) enzyme activity. Individuals who carry these variant alleles may have reduced plasma concentrations of endoxifen and benefit less from tamoxifen therapy. At this time, the FDA-approved drug label for tamoxifen does not discuss genetic testing for CYP2D6. The National Comprehensive Cancer Network (NCCN) does not recommend CYP2D6 testing as a tool to determine the optimal adjuvant endocrine strategy, and this recommendation is consistent with the 2010 guidelines from the American Society of Clinical Oncology (ASCO). In contrast, the Dutch Pharmacogenetics Working Group has made recommendations for tamoxifen therapy based on CYP2D6 genotypes. For both poor and intermediate metabolizers, their recommendation is to consider using aromatase inhibitors for postmenopausal women due to an increased risk for relapse of breast cancer with tamoxifen. They also recommend that intermediate metabolizers avoid the concomitant use of CYP2D6 inhibitors.
Thioridazine is an antipsychotic used in the treatment of schizophrenia and psychosis. Its use is reserved for patients who have failed to respond to or cannot tolerate other antipsychotics. Thioridazine has been shown to prolong the QT interval (the time taken for the heart ventricles to depolarize and repolarize) in a dose related manner. Drugs with this potential have been associated with the life-threatening ventricular tachycardia, ""torsades de pointes"". The CYP2D6 enzyme is involved in metabolizing thioridazine. About 7% of the population has reduced enzyme activity because of variants in the CYP2D6 gene. In individuals with low CYP2D6 activity, standard doses of thioridazine may lead to higher drug levels in the plasma, and increase the risk of cardiac arrhythmias. The FDA-approved drug label for thioridazine states that thioridazine is contraindicated in individuals who are known to have reduced levels of CYP2D6 activity. The label also states it is contraindicated to coadminister thioridazine with drugs that inhibit CYP2D6 (e.g., fluoxetine, paroxetine) or inhibit the metabolism of thioridazine (e.g., fluvoxamine, propranolol, and pindolol).
Tramadol is an analgesic used to treat moderate to moderately severe pain. It is a synthetic opioid, related to codeine, and is used to treat both acute and chronic pain. Tramadol is often prescribed for post-operative pain, and pain caused by cancer, osteoarthritis, and other musculoskeletal diseases. The CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, including tramadol. Individuals who carry two inactive copies of CYP2D6 are known as poor metabolizers and have higher plasma concentrations of tramadol compared with individuals who have two copies of normal activity alleles. Individuals who carry one or more reduced or inactive copies of CYP2D6 are known as intermediate metabolizers, and individuals who carry more than two active copies of CYP2D6 are known as ultrarapid metabolizers. The FDA states that the levels of tramadol are approximately 20% higher in poor metabolizers compared to extensive (“normal”) metabolizers, while concentrations of the tramadol metabolite, M1, are 40% lower. Inhibitors of CYP2D6, such as fluoxetine and amitriptyline, also inhibit the metabolism of tramadol, and the full pharmacological impact of these alterations of tramadol dose in terms of either efficacy or safety is unknown. A guideline from the Dutch Pharmacogenetics Working Group includes dose recommendations for poor metabolizers (either select an alternative drug—not oxycodone or codeine—or be alert to the symptoms of insufficient pain relief). It also contains dose recommendations for intermediate metabolizers (be alert to decreased efficacy of tramadol, consider increasing the dose and if the response is still inadequate, either select an alternative drug—not oxycodone or codeine, or be alert to the symptoms of insufficient pain relief) and ultrarapid metabolizers (either reduce the dose of tramadol by 30% and be alert to adverse drug events, or select an alternative drug e.g., acetaminophen, NSAID, morphine—not oxycodone or codeine).
The HER2 gene is overexpressed in 15-20% of breast cancers and is also overexpressed in some cases of gastric cancer. Overall, ""HER2 positive"" tumors are associated with a faster rate of growth and a poorer prognosis. The use of trastuzumab in treatment regimes improves outcomes, but adverse effects of therapy include cardiac toxicity. The FDA-approved drug label for trastuzumab states that trastuzumab should only be used to treat patients with tumors that have either HER2 protein overexpression or HER2 gene amplification, as determined by an accurate and validated FDA-approved assay, specific for the type of tumor tested (breast or gastric). This is because these are the only patients studied for whom benefit has been shown. A guideline from ASCO/CAP states that oncologists must request HER2 testing on every primary invasive breast cancer (and on a metastatic site, if stage IV and if specimen available) from a patient with breast cancer to guide decision to pursue HER2-targeted therapy. This should be especially considered for a patient who previously tested HER2 negative in a primary tumor and presents with disease recurrence with clinical behavior suggestive of HER2-positive or triple-negative disease.
Venlafaxine is an antidepressant used in the treatment of major depressive order, anxiety, and panic disorders. Venlafaxine belongs to the drug class of serotonin and norepinephrine reuptake inhibitors (SNRIs). The CYP2D6 enzyme metabolizes a quarter of all prescribed drugs, including venlafaxine. This enzyme converts venlafaxine to the active metabolite, O-desmethylvenlafaxine (ODV). Individuals who carry two inactive copies of CYP2D6 (""poor metabolizers"") may have decreased capacity to metabolize venlafaxine, resulting in less active metabolites in their system. In contrast, individuals who carry more than two copies of functional CYP2D6 alleles (""ultrarapid metabolizers"") may have an enhanced capacity to metabolize venlafaxine, resulting in more increased active metabolites in their system. The FDA states that because the total exposure of venlafaxine and ODV is similar in poor and extensive (normal) metabolizers, there is no need for different venlafaxine dosing regimens for these individuals. However, the Dutch Pharmacogenetics Working Group recommends that both poor and intermediate metabolizer genotypes should be treated with an alternative drug, or lower doses of venlafaxine based on clinical response and drug levels. For ultrarapid metabolizer genotypes, they recommend that either the dose of venlafaxine be increased up to 150% of the normal dose, or an alternative drug used.
Lipedema is a disorder of adipose tissue characterized by fat legs and orthostatic edema. Characteristically, the buttocks and other parts of the lower extremities are symmetrically enlarged owing to accumulation of excess fat and fluid. The condition affects women almost exclusively and, in most instances, represents an exaggeration of the female form (summary by Hines, 1952).
Senior-Loken syndrome is an autosomal recessive disease with the main features of nephronophthisis (NPHP; see 256100) and Leber congenital amaurosis (see 204000). Mutations in some of the same genes that cause nephronophthisis (see 256100) cause Senior-Loken syndrome. Genetic Heterogeneity of Senior-Loken Syndrome Other forms of SLSN include SLSN4 (606996), caused by mutation in the NPHP4 gene (607215) on chromosome 1p36; SLSN5 (609254), caused by mutation in the NPHP5 gene (IQCB1; 609237) on chromosome 3q13; SLSN6 (610189), caused by mutation in the NPHP6 gene (CEP290; 610142) on chromosome 12q21; SLSN7 (613615), caused by mutation in the SDCCAG8 gene (613524) on chromosome 1q43; SLSN8 (616307), caused by mutation in the WDR19 gene (608151) on chromosome 4p14; and SLSN9 (616629), caused by mutation in the TRAF3IP1 gene (607380) on chromosome 2q37. Another form of SLSN, SLSN3 (606995), has been mapped to a locus on chromosome 3q22, overlapping the NPHP3 locus (604387).
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of heart disease that usually appears in adulthood. ARVC is a disorder of the myocardium, which is the muscular wall of the heart. This condition causes part of the myocardium to break down over time, increasing the risk of an abnormal heartbeat (arrhythmia) and sudden death.ARVC may not cause any symptoms in its early stages. However, affected individuals may still be at risk of sudden death, especially during strenuous exercise. When symptoms occur, they most commonly include a sensation of fluttering or pounding in the chest (palpitations), light-headedness, and fainting (syncope). Over time, ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen. If the myocardium becomes severely damaged in the later stages of the disease, it can lead to heart failure.
Statins are among the most commonly prescribed drugs in the world to treat hypercholesterolemia and prevent cardiovascular diseases. They effectively lower cholesterol levels by inhibiting the HMG-CoA reductase to reduce cholesterol synthesis. Though well tolerated in general, the most common statin side effect is muscle pain. The symptoms range from mild muscle pain to fatal rhabdomyolysis, especially when statins are administered at higher doses and with certain other medications. A common coding SNP in the SLCO1B1 gene, rs4149056 or SLCO1B1*5, has been significantly associated with a marked increase in systemic exposure to simvastatin and risk of muscle toxicity. The overall effect size and significance of this association are striking for simvastatin compared to other statins. Patients with this specific variant in SLCO1B1 (a transporter of simvastatin) may require a lower simvastatin dose or consider an alternative statin as compared to patients who do not have this variant, and may consider routine creatine kinase (CK) surveillance. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has published a clinical dosing guideline for SLCO1B1 genotype and simvastatin dosing in Clinical Pharmacology & Therapeutics. This guideline is available on the PharmGKB website.
Omeprazole blocks the secretion of gastric acid and belongs to the drug class of proton pump inhibitors. It is used to treat gastroesophageal reflux disease (GERD), gastric ulcers, duodenal ulcers, erosive esophagitis, and other acid-related disorders. It is also used in the treatment of hypersecretory conditions, such as Zollinger-Ellison syndrome, and is used in combination with antibiotics to eradicate Helicobacter pylori (H. pylori) infection. CYP2C19 is the principal enzyme that metabolizes omeprazole to inactive metabolites. Approximately 3% of Caucasians and 15 to 20% of Asians have reduced or absent CYP2C19 enzyme activity (""poor metabolizers""). In these individuals, standard doses of omeprazole may lead to higher exposure to the drug and improved treatment outcomes. In contrast, individuals with increased CYP2C19 activity (""ultrarapid metabolizers"") may have an insufficient response to treatment as the active drug is inactivated at a faster rate. The FDA-approved drug label for omeprazole states that a dose reduction should be considered in the Asian population, particularly for the maintenance of healing of erosive esophagitis. The Pharmacogenetics Working Group of the Royal Dutch Association for the Advancement of Pharmacy (KNMP) has published dose alterations based on CYP2C19 genotype. For CYP2C19 poor metabolizers, they do not recommend altering the dose; however for ultrarapid metabolizers, they recommend being extra alert to an insufficient response to treatment. For the eradication of H. pylori in ultrarapid metabolizers, they recommend increasing the dose of omeprazole by 100–200%, and to consider the same dose increase for other conditions.
Warburg Micro syndrome is a rare autosomal recessive syndrome characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, cortical dysplasia, in particular corpus callosum hypoplasia, severe mental retardation, spastic diplegia, and hypogonadism (summary by Morris-Rosendahl et al., 2010). Genetic Heterogeneity of Warburg Micro Syndrome Warburg Micro syndrome-2 (WARBM2; 614225) is caused by mutation in the RAB3GAP2 gene (609275) on chromosome 1q41. WARBM3 (614222) is caused by mutation in the RAB18 gene (602207) on chromosome 10p12. WARBM4 (615663) is caused by mutation in the TBC1D20 gene (611663) on chromosome 20p13. See also Martsolf syndrome (212720), a clinically overlapping but milder autosomal recessive disorder caused by autosomal recessive mutation in the RAB3GAP2 gene. Handley et al. (2013) provided an overview of the disease variants identified in the RAB3GAP1, RAB3GAP2, and RAB18 genes, noting that a total of 144 families with WARBM and 9 families with Martsolf syndrome had been studied. Mutations were identified in RAB3GAP1 in 41% of cases, in RAB3GAP2 in 7% of cases, and in RAB18 in 5% of cases. Although RAB18 had not been linked to RAB3 pathways, Handley et al. (2013) stated that mutations in all 3 genes cause an indistinguishable phenotype, making it likely that there is some functional overlap.
Allopurinol is widely prescribed for the treatment of hyperuricemia and gout. An estimated 25-30% of gout patients in the UK and the US are treated with allopurinol. However, 0.1-0.4% of patients treated with allopurinol experience severe cutaneous adverse reactions (SCAR), including drug hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The genetic variant HLA-B*58:01, along with non-genetic factors, is known to be associated with this risk. Patients who are HLA-B*58:01-positive (having at least one copy of the HLA-B*58:01 allele) have a significantly increased risk of allopurinol-induced SCAR compared to those who are negative for this allele. It is still possible for a HLA-B*58:01 negative patient to develop SCAR on allopurinol. Guidelines regarding the use of pharmacogenomic tests in dosing for allopurinol have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Familial isolated pituitary adenoma (FIPA) is an inherited condition characterized by development of a noncancerous tumor in the pituitary gland (called a pituitary adenoma). The pituitary gland, which is found at the base of the brain, produces hormones that control many important body functions.Tumors that form in the pituitary gland can release excess levels of one or more hormones, although some tumors do not produce hormones (nonfunctioning pituitary adenomas). Those that do are typically distinguished by the particular hormones they produce. Prolactinomas are the most common tumors in FIPA. These tumors release prolactin, a hormone that stimulates breast milk production in females. Both women and men can develop prolactinomas, although they are more common in women. In women, these tumors may lead to changes in the menstrual cycle or difficulty becoming pregnant. Some affected women may produce breast milk, even though they are not pregnant or nursing. In men, prolactinomas may cause erectile dysfunction or decreased interest in sex. Rarely, affected men produce breast milk. Large prolactinomas can press on nearby tissues such as the nerves that carry information from the eyes to the brain (the optic nerves), causing problems with vision.Another type of tumor called somatotropinoma is also common in FIPA. These tumors release growth hormone (also called somatotropin), which promotes growth of the body. Somatotropinomas in children or adolescents can lead to increased height (gigantism), because the long bones of their arms and legs are still growing. In adults, growth of the long bones has stopped, but the tumors can cause overgrowth of the hands, feet, and face (acromegaly) as well as other tissues.Less common tumor types in FIPA include somatolactotropinomas, nonfunctioning pituitary adenomas, adrenocorticotropic hormone-secreting tumors (which cause a condition known as Cushing disease), thyrotropinomas, and gonadotropinomas. In a family with the condition, affected members can develop the same type of tumor (homogenous FIPA) or different types (heterogenous FIPA).In FIPA, pituitary tumors usually occur at a younger age than sporadic pituitary adenomas, which are not inherited. In general, FIPA tumors are also larger than sporadic pituitary tumors. Often, people with FIPA have macroadenomas, which are tumors larger than 10 millimeters.Familial pituitary adenomas can occur as one of many features in other inherited conditions such as multiple endocrine neoplasia type 1 and Carney complex; however, in FIPA, the pituitary adenomas are described as isolated because only the pituitary gland is affected.
Cold-induced sweating syndrome is characterized by problems with regulating body temperature and other abnormalities affecting many parts of the body. In infancy, the features of this condition are often known as Crisponi syndrome. Researchers originally thought that cold-induced sweating syndrome and Crisponi syndrome were separate disorders, but it is now widely believed that they represent the same condition at different times during life.Infants with Crisponi syndrome have unusual facial features, including a flat nasal bridge, upturned nostrils, a long space between the nose and upper lip (philtrum), a high arched roof of the mouth (palate), a small chin (micrognathia), and low-set ears. The muscles in the lower part of the face are weak, leading to severe feeding difficulties, excessive drooling, and breathing problems. Other physical abnormalities associated with Crisponi syndrome include a scaly skin rash, an inability to fully extend the elbows, overlapping fingers and tightly fisted hands, and malformations of the feet and toes. Affected infants startle easily and often tense their facial muscles into a grimace-like expression. By six months of age, infants with Crisponi syndrome develop unexplained high fevers that increase the risk of seizures and sudden death.Many of the health problems associated with Crisponi syndrome improve with time, and affected individuals who survive the newborn period go on to develop other features of cold-induced sweating syndrome in early childhood. Within the first decade of life, affected individuals begin having episodes of profuse sweating (hyperhidrosis) and shivering involving the face, torso, and arms. The excessive sweating is usually triggered by exposure to temperatures below about 65 or 70 degrees Fahrenheit, but it can also be triggered by nervousness or eating sugary foods. Paradoxically, affected individuals tend not to sweat in warmer conditions, instead becoming flushed and overheated in hot environments.Adolescents with cold-induced sweating syndrome typically develop abnormal side-to-side and front-to-back curvature of the spine (scoliosis and kyphosis, often called kyphoscoliosis when they occur together). Although infants may develop life-threatening fevers, affected individuals who survive infancy have a normal life expectancy.
The term 'not specified' was created for use in ClinVar so that submitters can convey the concept that a variant is benign, likely benign, or of uncertain significance for an unspecified set of disorders. This usage was introduced in 2014 to replace AllHighlyPenetrant.
Amitriptyline is a tricyclic that can be identified by the tertiary amine in its chemical structure. Tricyclics are commonly prescribed for psychological disorders and pain management. Genetic variants in both cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19) may affect treatment success of amitriptyline or other tricyclics with the tertiary amine functional group. Patients with poor metabolizer variants of either CYP2D6 or CYP2C19 may require reductions in dose or alternative agents in order to circumvent common adverse anticholinergic, central nervous system, or cardiac effects. Guidelines regarding the use of pharmacogenomic tests in dosing for amitriptyline and other tricyclics have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Autosomal recessive IRF8 deficiency, or IMD32B, results in a life-threatening pediatric syndrome characterized by monocyte and dendritic cell deficiency, myeloproliferation, and susceptibility to severe opportunistic infections, including disseminated BCG infection and oral candidiasis (Hambleton et al., 2011).
The epilepsy-aphasia spectrum is a group of conditions that have overlapping signs and symptoms. A key feature of these conditions is impairment of language skills (aphasia). The language problems can affect speaking, reading, and writing. Another feature of epilepsy-aphasia spectrum disorders is certain patterns of abnormal electrical activity in the brain, which are detected by a test called an electroencephalogram (EEG). Many people with conditions in this spectrum develop recurrent seizures (epilepsy), and some have mild to severe intellectual disability. The conditions in the epilepsy-aphasia spectrum, which all begin in childhood, include Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike-and-wave during sleep syndrome (ECSWS), autosomal dominant rolandic epilepsy with speech dyspraxia (ADRESD), intermediate epilepsy-aphasia disorder (IEAD), atypical childhood epilepsy with centrotemporal spikes (ACECTS), and childhood epilepsy with centrotemporal spikes (CECTS).LKS and ECSWS are at the severe end of the spectrum. Both usually feature a characteristic abnormal pattern of electrical activity in the brain called continuous spike and waves during slow-wave sleep (CSWS). This pattern occurs while the affected child is sleeping, specifically during deep (slow-wave) sleep.Most children with LKS develop normally in early childhood, although some speak later than their peers. However, affected children lose language skills beginning around age 5. This loss typically begins with verbal agnosia, which is the inability to understand speech. As LKS develops, the ability to express speech is also impaired. Approximately 70 percent of children with LKS have seizures, typically of a type described as focal (or partial) because the seizure activity occurs in specific regions of the brain rather than affecting the entire brain.About half of children with ECSWS develop normally in early childhood, while others have delayed development of speech and motor skills. Although children with ECSWS typically lose a range of previously acquired skills, including those involved in language, movement, learning, or behavior, not everyone with ECSWS has aphasia. Seizures occur in approximately 80 percent of children with ECSWS and can include a variety of types, such as atypical absence seizures, which involve short periods of staring blankly; hemiclonic seizures, which cause rhythmic jerking of one side of the body; or generalized tonic-clonic seizures, which cause stiffening and rhythmic jerking of the entire body.CECTS is at the mild end of the epilepsy-aphasia spectrum. Affected children have rolandic seizures; these seizures are triggered by abnormal activity in an area of the brain called the rolandic region, which is part of the cerebrum. The seizures, which usually occur during sleep, cause twitching, numbness, or tingling of the face or tongue, often causing drooling and impairing speech. In most people with CECTS, the seizures disappear by the end of adolescence. Most affected individuals develop normally, although some have difficulty coordinating the movements of the mouth and tongue needed for clear speech (dyspraxia) or impairment of language skills.The other conditions in the epilepsy-aphasia spectrum are less common and fall in the middle of the spectrum. Children with IEAD usually have delayed development or regression of language skills. Some have seizures and most have abnormal electrical activity in their brains during sleep, although it is not prominent enough to be classified as CSWS. ACECTS features seizures and developmental regression that can affect movement, language, and attention. Children with ACECTS have abnormal electrical activity in the brain that is sometimes classified as CSWS. ADRESD is characterized by focal seizures, speech difficulties due to dyspraxia, and learning disability.
Gentamicin is an aminoglycoside antibiotic that is commonly used to treat sepsis in premature infants. Brand names include Garamycin, Cidomycin, and Setpopal. Gentamicin is administered by injection to treat serious infections caused by Gram-negative bacteria (e.g., Pseudomonas aeruginosa, Proteus species, Escherichia coli, Klebsiella-Enterobacter-Serratia species, and Citrobacter species), and is used as an adjuvant treatment for infections caused by Gram-positive bacteria (e.g., Staphylococcus species). Gentamicin may also be used topically to treat ophthalmic and dermatological infections. In most patients, prolonged exposure to high gentamicin levels will cause ototoxicity (damage to the inner ear). However, in individuals who carry specific variants in the mitochondrial gene, MT-RNR1, a single dose of gentamicin can result in hearing loss. This toxicity occurs in genetically susceptible individuals even though the serum drug level is within therapeutic range. In most studies, 100% of individuals with the MT-RNR1 variant known as m.1555A>G (NC_012920.1:m.1555A>G) developed hearing loss after receiving aminoglycoside therapy. The onset of hearing loss varies, but once it occurs, the hearing loss is usually moderate to profound, bilateral, and irreversible. Currently, the FDA-approved drug label for gentamicin does not include a statement about MT-RNR1. However, a 2014 American College of Medical Genetics and Genomics (ACMG) guideline includes the following recommendation: “Single-gene testing may be warranted in cases in which the medical or family history, or presentation of the hearing loss, suggests a specific etiology. For example, testing for mitochondrial DNA mutations associated with aminoglycoside ototoxicity may be considered for individuals with a history of use of aminoglycoside antibiotics”.
Ivacaftor is the first FDA-approved drug designed to target a specific defect of the CFTR protein found in a subset of Cystic fibrosis (CF) patients. Hundreds of different variants within the CFTR gene have been identified. The G551D variant (rs75527207 G>A) results in defective gating at the plasma membrane and, in combination with another disease-causing CFTR allele, can result in CF disease phenotypes. Ivacaftor is designed to potentiate G115D-CFTR to improve symptoms in CF patients who carry this variant. Therapeutic guidelines for ivacaftor based on CFTR genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/drug/PA165950341).
Multiple myeloma is a cancer that develops in the bone marrow, the spongy tissue found in the center of most bones. The bone marrow produces red blood cells, which carry oxygen throughout the body; white blood cells, which form the body's defenses (immune system); and platelets, which are necessary for blood clotting.Multiple myeloma is characterized by abnormalities in plasma cells, a type of white blood cell. These abnormal cells multiply out of control, increasing from about one percent of cells in the bone marrow to the majority of bone marrow cells. The abnormal cells form tumors within the bone, causing bone pain and an increased risk of fractures. If the tumors interfere with nerves near the bones, numbness or weakness in the arms or legs can occur. Affected individuals may also experience a loss of bone tissue, particularly in the skull, spine, ribs, and pelvis. The deterioration of bone can result in an excess of calcium in the blood (hypercalcemia), which can lead to nausea and loss of appetite, excessive thirst, fatigue, muscle weakness, and confusion.The abnormal plasma cells in multiple myeloma produce proteins that impair the development of normal blood cells. As a result, affected individuals may have a reduced number of red blood cells (anemia), which can cause fatigue, weakness, and unusually pale skin (pallor); a low number of white blood cells (leukopenia), which can result in a weakened immune system and frequent infections such as pneumonia; and a reduced number of platelets (thrombocytopenia), which can lead to abnormal bleeding and bruising. Kidney problems can also occur in this disorder, caused by hypercalcemia or by toxic proteins produced by the abnormal plasma cells.People with multiple myeloma typically develop the disorder around age 65. Over time, affected individuals can develop life-threatening complications, but the rate at which this happens varies widely. Some affected individuals are diagnosed incidentally when tests are done for other purposes and do not experience symptoms for years.
RRM2B-related mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy (RRM2B-MDS) is a severe condition that begins in infancy and affects multiple body systems. It is associated with brain dysfunction combined with muscle weakness (encephalomyopathy). Many affected individuals also have a kidney dysfunction known as renal tubulopathy.Infants with RRM2B-MDS have weak muscle tone (hypotonia) and a failure to grow or gain weight at the expected rate (failure to thrive). Many have a smaller-than-normal head size (microcephaly). Due to muscle weakness, affected infants typically have difficulty controlling head movement and may have delayed development of other motor skills, such as rolling over or sitting. Weakness of the muscles used for breathing leads to serious breathing difficulties and can result in life-threatening respiratory failure. Most affected infants have a buildup of a chemical called lactic acid in the body (lactic acidosis), which can also be life-threatening.Some individuals with RRM2B-MDS have a digestion problem known as gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently. This disorder may lead to swallowing difficulties, vomiting, and diarrhea and can contribute to a failure to thrive. Less commonly, individuals with RRM2B-MDS develop seizures or hearing loss that is caused by nerve damage in the inner ear (sensorineural hearing loss).Because of the severity of the signs and symptoms, people with RRM2B-MDS usually live only into early childhood.
Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) is a form of HCHWA (see this term), a group of familial central nervous system disorders, characterized by severe cerebral amyloid angiopathy (CAA), hemorrhagic and non-hemorrhagic strokes and dementia.
Solitary necrotic tumor of the liver is a rare nonmalignant hepatic lesion characterized by a mass with a completely necrotic core often partially calcified, surrounded by a dense hyalinized fibrous capsule containing elastin fibers. Patients are usually asymptomatic but some may suffer from intermittent abdominal pain or discomfort.
Esophageal duplication cyst is a rare, congenital, non-syndromic esophageal malformation, most frequently located in the distal esophagus and usually diagnosed in childhood, characterized by tubular or spherical cystic masses that have a double layer of surrounding smooth muscle lined with squamous or enteric epithelium, are continuous or contiguous to the esophagus and may, or may not, communicate with the esophageal lumen. Patients are frequently asymptomatic, or could present with a wide range of symptoms including respiratory distress, failure to thrive, dysphagia, epigastric discomfort, vomiting, stridor, non-productive cough, and chest pain. Other more rare symptoms, such as cardiac arrhythmia, thoracic back pain, cystic hemorrgage and ulceration, and mediastinitis, have also been reported.
Tubular duplication of the esophagous is a rare congenital malformation where a second structure with individual lumen and stratified squamous mucosa and muscularis mucosa lies within or adjacent to the true esophagus causing dysphagia, nausea, vomiting, retrosternal pain and respiratory problems (stridor and recurrent pneumonia) and usually presenting in children.
Primary interstitial lung disease specific to childhood due to pulmonary surfactant protein anomalies is a group of interstitial lung diseases (ILD) induced by genetic mutations disrupting surfactant function and gas exchange in the lung. The disorders caused by these mutations affect full-term infants and older children and exhibit considerable overlap in their clinical and histologic presentation.
Hereditary angioedema type 1 (HAE 1) is a form of hereditary angioedema (see this term) characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.
Acquired angioedema type 2 (AAE2) is a type of acquired angioedema (AAE, see this term) characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.
Acquired angioedema type 1 (AAE 1) is a type of acquired angioedema (AAE) (see this term) characterized by acute edema in subcutaneous tissues, viscera and/or the upper airway.
Endocrine tumor of the appendix is the most common sporadic neoplasm of the appendix and the second most common type of digestive endocrine tumor, often with no specific clinical presentation. They are divided into either classic endocrine tumor of the appendix or the more aggressive goblet cell carcinoma (GCC; see these terms).
Primary hepatic neuroendocrine carcinoma (PHNEC) is a rare hepatic tumor that may manifest with abdominal pain or fullness, as well as diarrhea or weight loss. More than 10% of cases are asymptomatic and in rare cases a carcinoid syndrome may be observed.
Porphyria of doss or deficiency of delta-aminolevulinic acid dehydratase (DALAD) is an extremely rare form of acute hepatic porphyria (see this term) characterized by neuro-visceral attacks without cutaneous manifestations.
FRAXE is a form of nonsyndromic X-linked mental retardation (NS-XLMR) characterized by mild intellectual deficit. FRAXE is the most common form of NS-XLMR.
FRAXF syndrome was originally identified in a family with developmental delay and an expanded CCG repeat at the folate-sensitive FRAXF fragile site. Since this initial description, FRAXF has been associated with a range of manifestations but no clear phenotype has been established.
Bathing suit ichthyosis (BSI) is a rare variant of autosomal recessive congenital ichthyosis (ARCI; see this term) characterized by the presence of large dark scales in specific areas of the body.
Familial hypofibrinogenemia is a coagulation disorder characterized by mild bleeding symptoms following trauma or surgery due to a reduced plasma fibrinogen concentration.
Familial isolated congenital asplenia is a rare, non-syndromic, potentially life-threatening visceral malformation characterized by the absence of normal spleen function, resulting in a primary immunodeficiency. Typically, the condition manifests with severe, recurrent, overwhelming infections (especially pneumococcal sepsis) in otherwise apparently healthy infants. In adults with no history of severe sepsis in infancy, thrombocytosis may be the presenting sign. Howell-Jolly bodies on blood smears and an absent spleen on abdominal ultrasound examination are highly suggestive associated findings.
The association of X-linked Alport syndrome with leiomyomatosis of the esophagus, tracheobronchial tree or female genitals has been reported in more than 30 families.
This syndrome is characterised by chronic diarrhoea in infancy or childhood in association with intestinal glucoamylase deficiency.
Atresia of the urethra is a rare congenital bladder outlet obstruction, a fetal lower urinary tract obstruction (fetal LUTO), that is usually fatal. Unless there is some other egress for the urine to escape the bladder, such as patent urachus or anuro-rectal communication, these lesions are not compatible with renal development.
Sinus of Valsalva aneurysm (SVA) is a rare congenital heart malformation of one or more of the aortic sinuses, consisting of a dilation that when unruptured is usually asymptomatic but when ruptured presents with progressive exertional dyspnea, fatigue, chest pain and that can lead to congestive heart failure if left untreated.
, present in fish or cephalopods. Following its penetration in the human gastrointestinal tract, the parasite can cause gastrointestinal classified as acute (manifesting as abdominal pain, diarrhea, nausea and vomiting), chronic, or ectopic reactions or allergic manifestations (urticaria, angioedema, anaphylactic shock).
Dental ankylosis is a rare disorder characterized by the fusion of the tooth to the bone, preventing both eruption and orthodontic movement.
Pentasomy X is a sex chromosome anomaly caused by the presence of three extra X chromosomes in females (49,XXXXX instead of 46,XX).
Anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome is a multiple congenital anomalies syndrome, reported in the offsprings of a consanguineous couple and characterized by multiple congenital skeletal (dolichocephaly, skull asymmetry, camptodactyly, clubfoot), muscular (muscle hypoplasia), ocular (anophthalmia, buphthalmos, retinal detachment, aniridia (see this term)) and cardiac (prolapse of tricuspid valves, mitral and tricuspid insufficiency) abnormalities. An autosomal recessive inheritance with variable expressivity was suspected. There have been no further descriptions in the literature since 1992.
Lung agenesis - heart defect - thumb anomalies is a very rare syndrome characterized by unilateral complete or partial lung agenesis, congenital cardiac defects and ipsilateral thumb anomalies.
Arachnodactyly-intellectual disability-dysmorphism syndrome is characterized by moderate intellectual deficit, brachycephaly, typical facies (thin lips and microstomia), ectomorphic habitus with extremely long, thin fingers and toes, and hypoplastic external genitalia. It has been described in three patients.
Opsoclonus myoclonus syndrome (OMS) is a rare neuroinflammatory disease of paraneoplastic, parainfectious or idiopathic origin, characterized by opsoclonus, myoclonus, ataxia, and behavioral and sleep disorders.
Congenital atransferrinemia is a very rare hematologic disease caused by a transferrin (TF) deficiency and characterized by microcytic, hypochromic anemia (manifesting with pallor, fatigue and growth retardation) and iron overload, and that can be fatal if left untreated.
, a single celled parasite (ciliate protozoan) that is usually associated with intestinal infection in areas associated with pig rearing. It infects humans occasionally, mostly immunocompromised patients. Some infected people may have no symptoms or only mild diarrhea and abdominal discomfort but others may experience more severe symptoms reminiscent of an acute inflammation of the intestines. Symptoms of Balantidiasis may be similar to those of other infections that cause intestinal inflammation, for example, amoebic dysentery. On very rare occasions this bacterium may invade extra-intestinal organs, mostly the lungs. Metronidazole is the treatment of choice.
Congenital intrauterine infection-like syndrome is characterised by the presence of microcephaly and intracranial calcifications at birth accompanied by neurological delay, seizures and a clinical course similar to that seen in patients after intrauterine infection with Toxoplasma gondii, Rubella, Cytomegalovirus, Herpes simplex (so-called TORCH syndrome), or other agents, despite repeated tests revealing the absence of any known infectious agent.
Bothriocephalosis is a mammalian cosmopolitan intestinal parasitosis. In addition to non-specific digestive problems (nausea, abdominal pain, lack of appetite), bothriocephalosis provokes an anaemia caused by vitamin B12 deficiency that resembles Biermer anaemia (anaemia characterised by abnormally large red blood cells).
Branchio-skeleto-genital (BSG) syndrome is an extremely rare multiple congenital anomalies/dysmorphic syndrome, described in three boys from one family, and characterized by intellectual disability, hypertelorism, broad and flat nasal bridge, maxillary hypoplasia, mandibular prognathism, bifid uvula or partial cleft palate, multiple dental cysts, Schmorl nodes, fused cervical spinous processes, pectus excavatum, and penoscrotal hypospadias. There have been no further descriptions in the literature since 1971.
Autosomal dominant popliteal pterygium syndrome (AD-PPS) is a rare genetic malformative disorder characterized by cleft lip, with or without cleft palate, contractures of the lower extremities, abnormal external genitalia, syndactyly of fingers and/or toes, and a pyramidal skin fold over the hallux nail.
Bronchiolitis obliterans syndrome (BOS) is a lung disorder that is mainly associated with chronic allograft dysfunction after lung transplantation and that is characterized by inflammation and fibrosis of bronchiolar walls that reduce the diameter of the bronchioles and result in progressive and irreversible airflow obstruction.
Symmetrical thalamic calcifications are clinically distinguished by a low Apgar score, spasticity or marked hypotonia, weak or absent cry, poor feeding, and facial diplegia or weakness.
Chronic beryllium disease (CBD) is a granulomatous, interstitial lung disease that occurs in individuals who develop beryllium sensitization (BeS), a cell-mediated immune response to environmental and occupational beryllium exposure. BeS precedes the lung disease that may present with chronic dry cough, fatigue, weight loss, chest pain, and increasing dyspnea.
Maternally inherited cardiomyopathy and hearing loss is a mitochondrial disease described in two unrelated families to date that has a heterogeneous clinical presentation characterized by the association of progressive sensorineural hearing loss with hypertrophic cardiomyopathy and, in the majority of cases, encephalomyopathy symptoms such as ataxia, slurred speech, progressive external opthalmoparesis (PEO), muscle weakness, myalgia, and exercise intolerance.
A new leukoencephalopathy, the CACH syndrome (Childhood Ataxia with Central nervous system Hypomyelination) or VWM (Vanishing White Matter) was identified on clinical and MRI criteria. Classically, this disease is characterized by (1) an onset between 2 and 5 years of age, with a cerebello-spastic syndrome exacerbated by episodes of fever or head trauma leading to death after 5 to 10 years of disease evolution, (2) a diffuse involvement of the white matter on cerebral MRI with a CSF-like signal intensity (cavitation), (3) a recessive autosomal mode of inheritance, (4) neuropathologic findings consistent with a cavitating orthochromatic leukodystrophy with increased number of oligodendrocytes with sometimes ``foamy'' aspect.
Nephrogenic systemic fibrosis (NSF) is a rare systemic fibrosing condition observed in renally impaired patients and characterized by a hardening and thickening of the skin with fibrotic plaques or papules, pruritus, joint pain and stiffness, muscle weakness, limitation of range of motion, and yellowed eyes. It is generally associated with administration of gadolinium-based magnetic resonance imaging contrast agents (GBCA) in patients with kidney disease.
Cardiac anomalies-heterotaxy syndrome is characterised by non-compaction of the ventricular myocardium, bradycardia, pulmonary valve stenosis, and secundum atrial septal defect. Laterality sequence anomalies are also present. So far, the syndrome has been described in nine members from three generations of the same family. Transmission is autosomal dominant and linkage to chromosome 6p24.3-21.2 was reported.
, syndactyly of the toes, short fifth fingers with a single flexion crease and absence of the distal interphalangeal crease of the fourth finger) and moderate to severe intellectual deficit.
Macular amyloidosis (MA) is a rare chronic form of cutaneous amyloidosis (see this term), a skin disease characterized by the accumulation of amyloid deposits in the dermis, clinically characterized by pruritic hyperkeratotic gray-brown macules that give a rippled or reticulated pattern of pigmentation usually in the upper back and extensor sites of arms, forearms and legs, and histologically by the deposition of amyloid in the upper dermis and close to the basal cell layer of the epidermis. MA is commonly associated with other skin diseases, such as atopic dermatitis.
This syndrome is characterised by the presence of a unilateral angioma on the face and autistic developmental problems characterised by language delay and atypical social interactions.
Unilateral choanal atresia is a, usually sporadic, congenital anomaly that is more commonly seen in females than in males (2:1), where the nose is blocked by bony or soft tissue formed during embryologic development on only one side (more commonly on the right side) and which is characterized by nasal obstruction and rhinorrhea, usually presenting at birth but that may go undetected until a respiratory infection aggravates the condition.
Bilateral choanal atresia is a congenital anomaly that is usually sporadic (but some familial cases have been reported), is more commonly seen in females than in males (2:1), and where the nose is blocked on both sides by bony or soft tissue formed during embryological development. It is characterized by respiratory distress relieved by crying and rhinorrhea that presents at birth.
This syndrome is characterized by night blindness, skeletal abnormalities (sloping shoulders, joint hyperextensibility, minor radiological anomalies) and characteristic facies (periorbital anomalies, malar flatness, retrognathia).
X-linked cerebral adrenoleukodystrophy (X-CALD), a subtype of X-linked adrenoleukodystrophy (X-ALD, see this term), is a peroxisomal disease characterized by severe inflammatory demyelination in the brain, and often associated with adrenal insufficiency.
DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms) is a hypersensitivity reaction characterized by a generalized skin rash, fever, eosinophilia, lymphocytosis and visceral involvement (hepatitis, nephritis, pneumonitis, pericarditis and myocarditis) and, in some patients, reactivation of human herpes virus 6.
Secondary acute transverse myelitis (ATM) is characterized by focal inflammation within the spinal cord due to a known cause, usually an inflammatory disease.
Idiopathic acute transverse myelitis (ATM) is an immune-mediated inflammatory demyelinating disorder of the spinal cord with motor, sensory and autonomic involvement.
Jeavons syndrome is an idiopathic generalized form of reflex epilepsy characterized by childhood onset, unique seizure manifestations, striking light sensitivity, and possible occurrence of generalized tonic-clonic seizures.
Leukoencephalopathy with bilateral anterior temporal lobe cysts is a nonprogressive neurological disorder marked by intellectual deficit, spasticity and motor retardation associated with characteristic MRI findings of anterior bilateral temporal lobe cysts and multilobar leukoencephalopathy. So far, around 30 cases have been reported in the literature. Onset occurs in the first few months of life. Sensorineural deafness and microcephaly have also been reported. The etiology is unknown but an autosomal recessive mode of inheritance has been suggested.
Progressive cavitating leukoencephalopathy is characterized by acute episodes of neurological deficit (ataxia, dysarthria, seizures) with irritability and opisthotonus followed by either steady deterioration or alternating periods of rapid progression and prolonged periods of stability.
17q11.2 microduplication syndrome is characterized by dysmorphic features and intellectual deficit.
This syndrome is characterized by the association of sensorineural hearing impairment and peripheral neuropathy.
Charlie M syndrome is a rare bone developmental disorder which belongs to a group of oromandibular limb hypogenesis syndromes that includes hypoglossia-hypodactyly and glossopalatine ankylosis (see these terms). The major anomalies which occur commonly in this group are hypoplasia of the mandible, syndactyly and ectrodactyly, small mouth, cleft palate, hypodontia, and facial paralysis. Patients with Charlie M syndrome also present with hypertelorism, absent or conically crowned incisors, and variable degrees of hypodactyly of the hands and feet. There have been no further descriptions in the literature since 1976.
Joubert syndrome (JS) and related disorders (JSRD) are a group of developmental delay/multiple congenital anomaly syndromes in which the mandatory feature is the ``molar tooth sign'' (MTS), a complex midbrain-hindbrain malformation recognizable on brain imaging. The MTS is characterized by cerebellar vermis hypodysplasia, thickening and malorientation of the superior cerebellar peduncles and abnormally deep interpeduncular fossa.
This syndrome is characterized by congenital thrombocytopenia associated with the presence of large platelets.
Glossopalatine ankylosis is a disorder belonging to the group of oromandibular-limb hypogenesis syndromes (OLHS) and is characterised by the presence of an intraoral band of variable thickness attaching the tongue to the hard palate or maxillary alveolar ridge.
Median cleft of the upper lip and maxilla is a rare, congenital, developmental defect during embryogenesis characterized by a midline vertical cleft through the upper lip and premaillary bone (can also involve the nasal septum and central nervous system). The phenotypic spectrum is highly variable (ranging from a simple vermillion notch to a wide complete cleft) and hypo/hypertelorism, telecanthus, monophthalmia, flat or cleft nose, wide columella, median alveolar cleft and cranial malformations may be associated.
Familial calcium pyrophosphate deposition (CPPD) is a chronic inherited arthropathy characterized by chondrocalcinosis (CC; i.e. cartilage calcification), often associated with recurrent acute calcium pyrophosphate (CPP) crystal arthritis and polyarticular osteoarthritis (OA).
Lethal recessive chondrodysplasia is an extremely rare lethal form of chondrodysplasia characterized by severe micromelic dwarfism, short and incurved limbs with normal hands and feet, facial dysmorphism (disproportionately large skull, frontal prominence, slightly flattened nasal bridge and short neck), muscular hypotonia, hyperlaxity of the extremities, and a narrow thorax. Most patients die of respiratory distress during the first hours or weeks of life. There have been no further descriptions in the literature since 1988.
Otospondylomegaepiphyseal dysplasia (OSMED) is an inborn error of cartilage collagen formation characterized by sensorineural hearing loss, enlarged epiphyses, skeletal dysplasia with disproportionately short limbs, vertebral body anomalies and a characteristic facies.
Ring chromosome 10 syndrome is characterized by intellectual deficit, growth retardation, and various dysmorphic features. Less than 20 cases have been described. The main features are low birth weight, microcephaly, stubby nose with a prominent nasal bridge, hypertelorism, strabismus, wide-set nipples, single transverse palmar creases, and clinodactyly. Boys have undescended testes and hypoplastic scrotum. Congenital heart disease, hydronephrosis or renal hypoplasia was present in some of the cases.
Cerebrooculofacioskeletal (COFS) syndrome is a rare genetic disorder, belonging to a family of diseases of DNA repair, characterized by a severe sensorineural involvement.
Cogan syndrome (CS) is a rare autoimmune disorder of unknown origin characterized by inflammatory ocular disease (mainly interstitial keratitis) and vestibulo-auditory manifestations (mainly acute onset hearing loss, tinnitus and vertigo), in the setting of a negative work-up for syphilis, with a variable risk of developing into a systemic disease. Systemic manifestations may occur in more than 70% of cases.
Intellectual disability-hypoplastic corpus callosum-preauricular tag syndrome is characterised by a hypoplastic corpus callosum, microcephaly, severe intellectual deficit, preauricular skin tags, camptodactyly, growth retardation, and recurrent bronchopneumonia. It has been described in four patients in two families. Transmission is autosomal recessive.
Cranio-fronto-nasal dysplasia - Poland anomaly is a polymalformative syndrome characterised by craniosynostosis, Poland anomaly (see this term), cranio-fronto-nasal dysplasia, and genital and breast anomalies. Less than ten cases have been described so far.
Craniosynostosis, Dandy-Walker malformation and hydrocephalus is a malformation disorder characterized by sagittal craniosynostosis (see this term), Dandy-Walker malformation, hydrocephalus, craniofacial dysmorphism (including dolichocephaly, hypertelorism, micrognathia, positional ear deformity) and variable developmental delay. The inheritance pattern appears to be autosomal dominant.
Familial isolated dilated cardiomyopathy is a rare, genetically heterogeneous cardiac disease characterized by dilatation leading to systolic and diastolic dysfunction of the left and/or right ventricles, causing heart failure or arrhythmia.
Hereditary mixed polyposis syndrome (HMPS) describes an autosomal dominantly inherited large-bowel disease characterized by the presence of a mixture of hyperplastic, atypical juvenile and adenomatous polyps that are associated with an increased risk of developing colorectal cancer if left untreated.
Hemophagocytic syndrome (HPS) is a rare immune disease (see this term) and a potentially life-threatening disorder characterized by cytokine storm and overwhelming inflammation causing fever, hepatosplenomegaly, cytopenia, hypertriglyceridemia, hyperferritinemia, and hemophagocytosis in bone marrow, liver, spleen or lymph nodes. It can be either primary due to a genetic defect (primary hemophagocytic lymphohistiocytosis ; see this term), or secondary to malignancies, to infections, most commonly with viruses such as Epstein-Barr virus or cytomegalovirus, human immunodeficiency virus, or to autoimmune disorders such as systemic lupus erythematosus or adult-onset Still disease (secondary hemophagocytic lymphohistiocytosis) (see these termes).
Acral dystrophic epidermolysis bullosa is a very rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) characterized by blistering confined primarily to the hands and feet.
Dystrophic epidermolysis bullosa, nails only is a rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) that shows no blistering and that is characterized by dystrophic or absent nails.
Smouldering systemic mastocytosis is a type of systemic mastocytosis (SM; see this term). This clonal hematologic disease, with a slow progression, results in an accumulation of neoplastic mast cells in the visceral organs over time and patients present with splenomegaly, hypercellular marrow and, in some cases, urticaria pigmentosa-like skin lesions.
Castleman disease (CD) is a benign lymphoproliferative disorder that may present as a localized or multicentric form (see these terms). The clinical manifestations are heterogeneous, ranging from asymptomatic discrete lymphadenopathy to recurrent episodes of diffuse lymphadenopathy with severe systemic symptoms.
Cap polyposis (CP) is a rare colorectal disease characterized by multiple inflammatory polyps that predominantly affect the rectosigmoid area and that manifests primarily as rectal bleeding with abnormal transit, constipation and diarrhea.
Cataract-glaucoma syndrome is characterised by the association of total bilateral congenital cataract with the secondary occurrence of glaucoma appearing at ages varying between 10 and 40 years.
Isolated congenital auditory ossicle malformation is a rare, congential, middle ear anomaly characterized by, usually unilateral and sporadic, variations in the number, size and/or configuration of the ossicles, with no tympanic membrane and external ear abnormalities and no history of trauma or infection. Patients frequently present late, after schooling has started, with non- progressive, conductive hearing loss often associated with speech delay and poor school performance.
Hb Bart's hydrops fetalis is the most severe form of alpha-thalassemia (see this term) and is almost always lethal. It is characterized by fetal onset of generalized edema, pleural and pericardial effusions, and severe hypochromic anemia.
The 2p21 microdeletion syndrome consists of cystinuria, neonatal seizures, hypotonia, severe growthand developmental delay, facial dysmorphism, and lactic acidemia.
Febrile infection-related epilepsy syndrome (FIRES) describes an explosive-onset, potentially fatal acute epileptic encephalopathy that develops in previously healthy children and adolescents following the onset of a non-specific febrile illness.
Xp22.3 microdeletion syndrome is a microdeletion syndrome resulting from a partial deletion of the chromosome X. Phenotype is highly variable (depending on length of deletion), but is mainly characterized by X linked ichthyosis, mild-moderate intellectual deficit, Kallmann syndrome, short stature, chondrodysplasia punctata and ocular albinism. Epilepsy, attention deficit-hyperactivity disorder, autism and difficulties with social communication can be associated.
Male sterility due to chromosome Y deletion is characterized by a severe deficiency of spermatogenesis. Chromosome Y deletions are a frequent genetic cause of male infertility.
Neutral lipid storage disease (NLSD) refers to a group of diseases characterized by a deficit in the degradation of cytoplasmic triglycerides and their accumulation in cytoplasmic lipid vacuoles in most tissues of the body. The group is heterogeneous: currently cases of NLSD with icthyosis (NLSDI/Dorfman-Chanarin disease; see this term) and NLSD with myopathy (NLSDM/neutral lipid storage myopathy; see this term) can be distinguished.
Bazex syndrome is a rare paraneoplastic syndrome characterized by acral psoriasiform lesions.
Odontochondrodysplasia, also called Goldblatt syndrome, is a very rare syndrome associating chondrodysplasia with dentinogenesis imperfecta.
Diencephalic syndrome (DS) is a rare condition characterized by profound emaciation and failure to thrive (with normal caloric intake and normal linear growth), hyperalertness, hyperkinesias and euphoria, in the presence of hypothalamic tumors.
Idiopathic dilatation of the right atrium (IDRA) is a rare congenital heart malformation of unknown etiology that is characterized by an extremely dilated right atrium, and that is usually asymptomatic and fortuitously discovered by echocardiography or chest radiography, and can be sometimes associated with other anomalies such as atrial arrhythmias (e.g. atrial flutter, atrial fibrillation, supraventricular tachycardia), severe tricuspid regurgitation, or atrial thrombus that could lead to potentially life-threatening thromboembolic complications.
Congenital neuronal ceroid lipofuscinosis (CNCL) is a severe form of neuronal ceroid lipofuscinosis (NCL; see this term) with onset at birth characterized by primary microcephaly, neonatal epilepsy, and death in early infancy.
Primary peritoneal carcinoma (PPC) is a rare malignant tumor of the peritoneal cavity of extra-ovarian origin, clinically and histologically similar to advanced-stage serous ovarian carcinoma (see this term).
Autosomal recessive centronuclear myopathy (AR-CNM) is an inherited neuromuscular disorder defined by numerous centrally placed nuclei on muscle biopsy and clinical features of a congenital myopathy.
Severe hemophilia B is a form of hemophilia B (see this term) characterized by a large deficiency of factor IX leading to frequent spontaneous hemorrhage and abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.
Moderately severe hemophilia B is a form of hemophilia B (see this term) characterized by factor IX deficiency leading to abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.
Mild hemophilia B is a form of hemophilia B (see this term) characterized by a small deficiency of factor IX leading to abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.
Moderately severe hemophilia A is a form of hemophilia A (see this term) characterized by factor VIII deficiency leading to abnormal bleeding as a result of minor injuries, or following surgery or tooth extraction.
Woolly hair is a rare congenital abnormality of the structure of the scalp hair marked by extreme kinkiness of the hair.
Rectal duplication is a rare congenital anorectal malformation characterized by an egg-like, cystic, mucus-filled mass, composed of intestinal mucosal lining and smooth muscle tissue. Commonly they present in childhood with symptoms of recurrent urinary tract infections, gastroenteritis, obstruction, perianal sepsis and rectal bleeding. Drainage of mucus or pus from the anus is also a typical presenting sign. The majority are found in the retro-rectal space where they communicate with, or are contiguous to, the rectum.
Severe congenital nemaline myopathy is a severe form of nemaline myopathy (NM; see this term) characterized by severe hypotonia with little spontaneous movement in neonates.
Intermediate nemaline myopathy is a type of nemaline myopathy (NM; see this term) that shows features of typical NM (see this term) in neonates with a more severe progression.
Typical nemaline myopathy is a moderate neonatal form of nemaline myopathy (NM; see this term) characterized by facial and skeletal muscle weakness and mild respiratory involvement.
Lissencephaly (LIS) due to TUBA1A mutation is a congenital cortical development anomaly due to abnormal neuronal migration involving neocortical and hippocampal lamination, corpus callosum, cerebellum and brainstem. A large clinical spectrum can be observed, from children with severe epilepsy and intellectual and motor deficit to cases with severe cerebral dysgenesis in the antenatal period leading to pregnancy termination due to the severity of the prognosis.
Idiopathic bilateral vestibulopathy is a rare otorhinolaryngologic disease characterized by dysfunction of both peripheral labyrinths or of the eighth nerves, which presents with persistent unsteadiness of gait (particularly in darkness, during eye closure or under impaired visual conditions, or when standing/walking on uneven, soft or wobbly ground) and oscillopsia associated with head movements. The disease may be progressive, presenting no episodes of vertigo, or sequential, presenting recurrent episodes of vertigo.
Deletion 6q16 syndrome is a Prader-Willi like syndrome characterized by obesity, hyperphagia, hypotonia, small hands and feet, eye/vision anomalies, and global developmental delay.
This syndrome associates gingival fibromatosis with dental abnormalities including generalized thin hypoplastic amelogenesis imperfecta, intrapulpal calcifications, and delay of tooth eruption.
Trisomy 5p is a chromosomal abnormality resulting from the duplication of a segment of variable size of the short arm of chromosome 5, which usually involves the distal band 5p15. The clinical presentation is variable but is always associated with severe intellectual deficit.
Distal trisomy of the short arm of chromosome 6 is characterized by pre- and postnatal growth retardation, a pattern of specific facial features (mostly of the eyes), microcephaly, and developmental delay.
Fibular dimelia-diplopodia syndrome is a rare developmental anomaly.
Thoraco-abdominal enteric duplication is a rare, syndromic intestinal malformation characterized by single or multiple smooth-walled, often tubular, cystic lesions, which on occasion contain ectopic gastric mucosa, located in the thorax (usually in the posterior mediastinum and to the right of the midline) and in the abdomen. Infants usually present with respiratory distress and older patients with heartburn, abdominal pain, vomiting and/or malena. Vertebral anomalies in the lower cervical spine, with CNS involvement, are frequently present and complications, such as bowel obstruction, perforation and intussusception, have also been reported.
45,X/46,XY mixed gonadal dysgenesis (45,X/46,XY MGD) is a disorder of sex development (DSD) associated with a numerical sex chromosome abnormality resulting from Y-chromosome mosaicism and leading to abnormal gonadal development.
gene (Xq28), encoding coagulation factor VIII.
gene (Xq28), encoding coagulation factor IX.
Embryonal sarcoma of the liver is a rare primary malignant hepatic neoplasm of childhood of mesenchymal origin. It can rarely occur in adults. It is characterized by abdominal mass, right upper quadrant or epigastric pain, nausea, anorexia, intermittent fever or headache.
This newly described syndrome is characterized by osteosclerosis, developmental delay and craniosynostosis (see this term).
Primary cutaneous gamma/delta-positive T-cell lymphoma is a rare, usually aggressive, subtype of cutaneous T-cell lymphoma characterized by infiltration of the epidermis, dermis or subcutaneous tissue by a clonal population of mature, gamma/delta positive cytotoxic T-cells. Typically it presents with ulcerating plaques, tumors, or subcutaneous nodules on the skin of the extremities, however, frequent involvement of mucosal and extranodal sites (such as the nasal cavity, gastrointestinal tract or lungs) is also observed. Cases associated with panniculitis may present with hemophagocytic syndrome (abrupt onset of fever, rash, cytopenia, hepatosplenomegaly and neurological compromise). Infiltration of lymph nodes, spleen and bone marrow is uncommon and resistance to multilineage chemotherapy is reported.
Autosomal dominant spondylocostal dysostosis is a very rare and mild form of spondylocostal dysostosis characterized by vertebral and costal segmentation defects, often with a reduction in the number of ribs.
Complete septate uterus is a rare, non-syndromic uterovaginal malformation characterized by a uterus that has a longitudinal septum which elongates from the uterine fundus to the internal or external cervical os. Most often women are asymptomatic, however dysmenorrhoea, unilateral obstruction, and endometriosis could be observed. Unlike urinary tract abnormalities, which are very rarely associated, poor reproductive outcome is frequent.
Partial septate uterus is a rare, non-syndromic uterovaginal malformation characterized by a uterus that has a longitudinal septum which extends from the uterine fundus and does not reach the internal cervical os (variable lengths and widths may be observed). Although frequently asymptomatic, an increased risk of poor reproductive outcome has been observed. Urinary tract abnormalities are very rarely associated.
Paget disease of the nipple describes a rare presentation of breast cancer, seen most frequently in women aged 50-60, manifesting with nipple drainage and itching, erythema, crusty and excoriated nipple, thickened plaques, and hyperpigmentation (less frequently). It is due to tumor cells invading the nipple-areola complex and represents 1-3% of all new breast cancer diagnoses.
Growth hormone insensitivity syndrome (GHIS) is a group of diseases characterized by marked short stature associated with normal or elevated growth hormone (GH) concentrations, which fail to respond to exogenous GH administration. GHIS comprises growth delay due to IGF-1 deficiency, growth delay due to IGF-1 resistance, Laron syndrome, short stature due to STAT5b deficiency and primary acid-labile subunit (ALS) deficiency (see these terms).
Pulmonary arterial hypertension (PAH) is a group of diseases characterized by elevated pulmonary arterial resistance leading to right heart failure. PAH is progressive and potentially fatal. PAH may be idiopathic and/ or familial, or induced by drug or toxin (drug-or toxin-induced PAH, see these terms) or associated with other diseases like congenital heart disease, connective tissue disease, HIV, schistosomiasis, portal hypertension (PAH associated with other disease, see this term).
Polymalformative genetic syndrome with increased risk of developing cancer (PGSIRC) comprises a wide range of syndromes characterized by congenital malformations with a high risk of developing tumors including up to 50 different rare diseases.
Primary biliary cholangitis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure.
Focal Dystonia is a rare neurologic movement disorder characterized by sustained muscle contractions of a single body region, usually producing twisting and repetitive movements or abnormal postures or positions.
Jalili syndrome is characterized by the association of amelogenesis imperfecta (AI; see this term) and cone-rod retinal dystrophy (CORD; see this term).
Melorheostosis with osteopoikilosis is a rare sclerosing bone dysplasia, combining the clinical and radiological features of melorheostosis and osteopoikilosis (see these terms), that has been reported in some families with osteopoikilosis and that is characterized by a variable presentation of limb pain and deformities.
ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing syndrome (CS; see this term) characterized by nodular enlargement of both adrenal glands (multiple nodules above 1 cm in diameter) that produce excess cortisol and features of adrenocorticotropic hormone (ACTH) independent CS (see this term).
Indomethacin embryofetopathy refers to the manifestations that may be observed in a fetus or newborn when the mother has taken indomethacin, a potent prostaglandin inhibitor and tocolytic agent that can cross placenta, during pregnancy. Reported adverse fetal/neonatal effects include decreased renal function resulting in oligohydramnios, closure of the ductus arteriosus, and delayed cardiovascular adaptation at birth. These effects are usually transient and reversible. Indomethacin may also be a risk factor for cerebral injury (periventricular leukomalacia) and necrotizing enterocolitisin preterm infants.
10th percentile), a unique cluster of minor facial anomalies (short palpebral fissures, flat and smooth philtrum, and thin upper lip) and severe central nervous system (CNS) abnormalities including microcephaly, and cognitive and behavioral impairment (intellectual disability, deficit in general cognition, learning and language, executive function, visual-spatial processing, memory, and attention).
Foetal methylmercury syndrome is characterised by a group of symptoms that may be observed in a foetus or newborn when the mother was exposed during pregnancy to excessive amounts of methylmercury.
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Toluene embryopathy is a neurodevelopmental teratologic syndrome due to prenatal exposure to toluene. The disease is characterized by prematurity, low birth weight, dysmorphic features (short palpebral fissures, deep set eyes, low set ears, mid-facial hypoplasia, flat nasal bridge, thin upper lip, micrognathia, spatulate fingertips and small fingernails), central nervous system dysfunctions (intellectual disability, microcephaly, language impairment, hyperactivity, visual dysfunction) and postnatal growth delay. Prenatal exposure to toluene occurs as a result of incidental occupational exposure or solvent abuse during pregnancy. The features of toluene embryopathy often overlap with those seen in fetal alcohol syndrome (see this term).
Methimazole embryopathy is a teratogenic embryofetopathy that results from maternal exposition to methimazole (MMI; or the parent compound carbimazole) in the first trimester of pregnancy. MMI is an antithyroid thionamide drug used for the treatment of Graves' disease. In the infant, MMI may result in choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, congenital heart disease (such as ventricular septal defect), renal system malformations and aplasia cutis (see these terms). Additional features that may be observed include facial dysmorphism (short upslanting palpebral fissures, a broad nasal bridge with a small nose and a broad forehead) and athelia/hypothelia.
Herpes simplex virus encephalitis (HSE) is caused by the infection of the central nervous system by Herpes simplex virus (HSV) that could have a devastating clinical course and a potentially fatal outcome particularly with delay or lack of treatment. HSV often involves the frontal and temporal lobes, usually asymmetrically, resulting in personality changes, cognitive impairment, aphasia, seizures, and focal weakness.
Infant epilepsy with migrant focal crisis is characterized by early-onset progressive encephalopathy with migrant, continuous myoclonus. Three cases have been reported. The focal continuous myoclonus appeared during the first months of life. Prolonged bilateral myoclonic seizures and generalized tonic-clonic seizures occurred later. Subsequently, a progressive encephalopathy with hypotonia and ataxia appeared. Cortical atrophy was revealed by computed tomography (CT) scan and magnetic resonance imaging (MRI). The aetiology is unknown.
Rolandic epilepsy (RE) is a focal childhood epilepsy characterized by seizures consisting of unilateral facial sensory-motor symptoms, with electroencephalogram (EEG) showing sharp biphasic waves over the rolandic region. It is an age-related epilepsy, with excellent outcome.
Benign familial neonatal epilepsy (BFNE) is a rare genetic epilepsy syndrome characterized by the occurrence of afebrile seizures in otherwise healthy newborns with onset in the first few days of life.
Hereditary hypercarotenemia and vitamin A deficiency is an extremely rare metabolic disorder characterized clinically by skin discoloration, elevated levels of carotene and low levels of vitamin A described in fewer than 5 patients to date.
Isolated autosomal dominant hypomagnesemia, Glaudemans type (IADHG) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by low serum magnesium (Mg) values but normal urinary Mg values. The typical clinical features are recurrent muscle cramps, episodes of tetany, tremor, and muscle weakness, especially in distal limbs. The disease is potentially fatal.
Paradas type congenital myopathy is an early-onset form of dysferlinopathy presenting with postnatal hypotonia, weakness in the proximal lower limbs and neck flexor muscles at birth and delayed motor development.
Thiamine-responsive encephalopathy is a Wernicke-like encephalopathy (see this term) characterized by seizures responsive to high doses of thiamine.
3-hydroxy-3-methylglutaric aciduria (3HMG) is an organic aciduria, due to deficiency of 3-hydroxy-3-methylglutaryl-CoA-lyase (a key enzyme in ketogenesis and leucine metabolism) usually presenting in infancy with episodes of metabolic decompensation triggered by periods of fasting or infections, which when left untreated are life-threatening and may lead to neurological sequelae.
Cleft lip/palate-deafness-sacral lipoma syndrome is characterised by cleft lip/palate, profound sensorineural deafness, and a sacral lipoma. It has been described in two brothers of Chinese origin born to non consanguineous parents. Additional findings included appendages on the heel and thigh, or anterior sacral meningocele and dislocated hip. The mode of inheritance is probably autosomal or X-linked recessive.
A laryngo-tracheo-esophageal cleft (LC) is a congenital malformation characterized by an abnormal, posterior, sagittal communication between the larynx and the pharynx, possibly extending downward between the trachea and the esophagus.
Cleft palate- short stature- vertebral anomalies is a multiple congenital anomalies syndrome described in a father and son characterized by the association of cleft palate, peculiar facies (asymmetrical appearance, inner epicanthal folds, short nose, anteverted nostrils, low and back-oriented ears, thin upper lip and micrognathism), short stature, short neck , vertebral anomalies and intellectual disability. The transmission is presumed to be autosomal dominant. There have been no further descriptions in the literature since 1993.
Sternal cleft (SC) is a rare idiopathic congenital thoracic malformation characterized by a sternal fusion defect, that can be complete or partial (either superior or inferior), that is usually asymptomatic in the neonatal period (apart from a paradoxical midline thoracic bulging) but that can lead to dyspnea, cough, frequent respiratory infections and increased risk of trauma-related injury to the heart, lungs and major vessels if left untreated.
Idiopathic pulmonary fibrosis (IPF) is a nonneoplastic pulmonary disease that is characterized by the formation of scar tissue within the lungs in the absence of any known cause.
Congenital respiratory-biliary fistula (RBF) is a rare developmental defect characterized by an anomalous connection of trachea or bronchus with left hepatic duct presenting with respiratory distress, recurrent respiratory infections and biliary expectoration or vomitus.
Osteochondritis of tarsal/metatarsal bone is a very rare form of osteochondritis dissecans characterized by generally self-limiting bone lesions that may cause pain and swelling often localized at the tarsal navicular bone
Progressive non-infectious anterior vertebral fusion (PAVF) is an early childhood spinal disorder characterized by the gradual onset of thoracic and/or lumbar spine ankylosis often in conjunction with kyphosis with distinctive radiological features.
Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a hereditary disorder of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzyme deficiency.
Malignant non-dysgerminomatous germ cell tumor of ovary is a rare malignant germ cell tumor of ovary (see this term) arising from germ cells in the ovary, frequently unilateral at diagnosis, usually presenting during adolescence with pelvic mass, fever, vaginal bleeding and acute abdomen, with certain subtypes being occasionally associated with isosexual precocity, virilization, hyperthyroidism or carcinoid syndrome (see this term). Histologically they comprise the following: embryonal carcinoma, Yolk sac tumor, polyembryoma and mixed germ cell tumor.
Symptomatic forms of Duchenne and Becker muscular dystrophies (DMD and BMD: see these terms) in females carriers are characterized by variable degrees of muscle weakness due to progressive skeletal myopathy, sometimes associated with dilated cardiomyopathy or left ventricle dilation.
Subacute inflammatory demyelinating polyneuropathy (SIDP) is a subacute progressive symmetric sensorial and/or motor disorder characterized by muscular weakness with impaired sensation, absent or diminished tendon reflexes and elevated cerebrospinal fluid (CSF) proteins. SIDP is an intermediate form between Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP; see these terms).
Crouzon disease is characterized by craniosynostosis and facial hypoplasia.
Eosinophilic gastroenteritis (EGE) is a rare benign gastrointestinal disease characterized by the presence of abnormal and nonspecific gastro-intestinal (GI) manifestations, associated with an eosinophilic infiltration of the GI tract, which can affect several segments and involve several layers within the GI wall.
Cerebral gigantism-jaw cysts syndrome is characterised by cerebral gigantism associated with a jaw cyst basal cell naevoid syndrome.
Solitary rectal ulcer syndrome (SRUS) is a rare rectal disease characterized by rectal bleeding, abdominal pain, passage of mucus, sensation of incomplete evacuation, straining at defecation and rectal prolapsed, secondary to ischemic changes in the rectum.
, a recently discovered coccidia that was initially described in Peru and then in most intertropical zones. Infection occurs through ingestion of contaminated food or water and leads to abdominal pain, anorexia and diarrhoea, which may resolve spontaneously in immunocompetent individuals but may persist in a chronic form in immunocompromised subjects, leading to a decline in their general state of health.
Pulmonary fibrosis - hepatic hyperplasia - bone marrow hypoplasia, also named ?trimorphic syndrome? (i.e. three (inherited) morbidities, pulmonary, hepatic and cytopenia), is a rare disease reported in 4 cases to date, manifesting with idiopathic pulmonary fibrosis, hepatic nodular regenerative hyperplasia leading to portal hypertension and thrombocytopenia due to bone marrow hypoplasia. The condition was associated with 100% mortality.
Adult hepatocellular carcinoma is the most common primary liver cancer of adulthood. Derived from well-differentiated hepatocytes, it often develops from chronic liver cirrhosis which is most often due to hepatitis B and C virus or alcohol abuse. Symptoms are hepatic mass, abdominal pain and, in advanced stages, jaundice, cachexia and liver failure.
Diffuse neonatal hemangiomatosis is a rare vascular tumor from unknown origin characterized by multiple, progressive, rapidly growing cutaneous hemangiomas (e.g. in the scalp, face, trunk and extremities) associated with widespread visceral hemangiomas in the liver, lungs, gastrointestinal tract, brain, and meninges.
Hennekam-Beemer syndrome is characterized by the association of skin mastocytosis (appearing as diffuse pigmentation), short stature, microcephaly, conductive hearing loss, and dysmorphic features. It has been described in only two (female) cases: one with normal mental development born to consanguineous parents and the other with severe psychomotor retardation born to unrelated parents. The mode of inheritance is most likely autosomal recessive.
Salivary gland type cancer of the breast describes a group of uncommon neoplasms, usually seen in the salivary glands but occurring in the breast, with a variable clinicopathologic spectrum and divided into those with myoepithelial differentiation and those without. This group includes mammary adenoid cystic carcinoma, adenoid cystic carcinoma (see this term), mucoepidermoid carcinoma, acinic cell carcinoma, polymorphous low-grade adenocarcinoma and oncocytic carcinoma.
Leiomyosarcoma of the cervix uteri is a rare, malignant mesenchymal tumor of smooth muscle origin, macroscopically appearing as a large, poorly circumscribed mass, often protruding from the cervical canal or expanding it circumferentially. The most common presenting symptoms are vaginal discharge or bleeding, pain in the lower abdomen and a bulky cervical mass. There is a reported tendency to metastatsize hematogenously, especially to the lungs, peritoneum, bones and the liver.
Osteogenesis imperfecta type I is a mild type of osteogenesis imperfecta (OI; see this term), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures.
Osteogenesis imperfecta type V is a moderate type of osteogenesis imperfecta (OI; see this term), a genetic disorder characterized by increased bone fragility, low bone mass and susceptibility to bone fractures with variable severity. OI type V is characterized by mild to moderate short stature, dislocation of the radial head, mineralized interosseous membranes, hyperplasic callus, white sclera and no dentinogenesis imperfecta (DI; see this term).
5-fluorouracil (5-FU) poisoning is a rare intoxication caused by the prolonged, low-dose administration of 5-FU, which is the mainstay of both adjuvant and advanced-disease chemotherapy regimens in colon cancer. 5-FU poisoning is characterized by gastrointestinal (nausea, emesis, diarrhea, anorexia, stomatitis) and hematologic (myelosuppression) toxicities as well as mucositis, alopecia and, occasionally, palmar-plantar dysesthesia (more commonly known as hand-foot syndrome). Women have been reported to experience more 5-FU-related toxicity than men.
Mucopolysaccharidosis type 2 (MPS2, see this term), severe form (MPS2S), is associated with a massive accumulation of glycosaminoglycans and a wide variety of symptoms including a rapidly progressive cognitive decline; it is most often fatal in the second or third decade.
Mucopolysaccharidosis type 2, attenuated form (MPS2att), the less severe form of MPS2 (see this term), leads to a massive accumulation of glycosaminoglycans and a wide variety of symptoms including distinctive facies, short stature, cardiorespiratory and skeletal findings. It is differentiated from mucopolysaccharidosis type 2, severe form (see this term) by the absence of cognitive decline.
Limbic encephalitis with anti-N-methyl-D-aspartate (NMDA) receptor antibodies is a recently described type of encephalitis (see this term) affecting young women with teratoma of ovary (see this term) and associated with antibodies that react with neuronal cell surface auto-antigens.
Acute infantile liver failure due to mtDNA-encoded proteins synthesis defect is a very rare mitochondrial respiratory chain deficiency described in fewer than 10 infants, primarily of middle Eastern descent, and characterized clinically by transient but life-threatening liver failure with elevated liver enzymes, jaundice, vomiting, coagulopathy, hyperbilirubinemia, and lactic acidemia.
Pulmonary interstitial glycogenosis (PIG) is a rare non-lethal pediatric form of interstitial lung disease (ILD, see this term).
Infantile systemic hyalinosis (ISH) is a very rare disorder belonging to the heterogeneous group of genetic fibromatoses and is characterized by progressive joint contractures, skin abnormalities, severe chronic pain and widespread deposition of hyaline material in many tissues such as the skin, skeletal muscle, cardiac muscle, gastrointestinal tract, lymph nodes, spleen, thyroid, and adrenal glands.
This syndrome is characterized by the association of congenital hydrocephalus, centripetal obesity, hypogonadism, intellectual deficit and short stature.
Anti-HLA hyperimmunization is an increase in anti-HLA antigens mostly seen in chronic renal failure (CRF) patients that have undergone hemodialysis and polytransfusion.
Diffuse cutaneous systemic sclerosis (dcSSc) is a subtype of Systemic Sclerosis (SSc; see this term) characterized by truncal and acral skin fibrosis with an early and significant incidence of diffuse involvement (interstitial lung disease, oliguric renal failure, diffuse gastrointestinal disease, and myocardial involvement).
Limited cutaneous systemic sclerosis (lcSSc) is a subtype of systemic sclerosis (SSc; see this term) characterized by the association of Raynaud's phenomenon with skin fibrosis limited to the hands, face, feet and forearms.
Limited systemic sclerosis (lSSc) (or SSc sine scleroderma) is a subset of systemic sclerosis (SSc; see this term) characterized by organ involvement in the absence of fibrosis of the skin.
Rare hereditary hemochromatosis comprises the rare forms of hereditary hemochromatosis (HH), a group of diseases characterized by excessive tissue iron deposition. These rare forms are hemochromatosis type 2 (juvenile), type 3 (TFR2-related), and type 4 (ferroportin disease) (see these terms). Hemochromatosis type 1 (also called classic hemochromatosis; see this term) is not a rare disease.
Joubert syndrome with ocular defect is, along with pure JS, the most frequent subtype of Joubert syndrome and related disorders (JSRD, see these terms) characterized by the neurological features of JS associated with retinal dystrophy.
Joubert syndrome with renal defect is a rare subtype of Joubert syndrome and related disorders (JSRD, see this term) characterized by the neurological features of JS associated with renal disease, in the absence of retinopathy.
Dermatomyositis (DM) is a type of idiopathic inflammatory myopathy characterized by evocative skin lesions and symmetrical proximal muscle weakness.
Rothmund-Thomson syndrome type 1 is a subform of Rothmund-Thomson syndrome (RTS; see this term) presenting with a characteristic facial rash (poikiloderma) and frequently associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, and rapidly progressive bilateral juvenile cataracts. In contrast to RTS2 (see this term), patients with RTS1 do not appear to have an increased risk of developing cancer.
Rothmund-Thomson syndrome type 2 is a subform of Rothmund-Thomson syndrome (RTS; see this term) presenting with a characteristic facial rash (poikiloderma) and frequently associated with short stature, sparse scalp hair, sparse or absent eyelashes and/or eyebrows, congenital bone defects and an increased risk of osteosarcoma in childhood and squamous cell carcinoma later in life.
Acrocephalopolydactyly, also known as Elejalde syndrome, is an extremely rare lethal autosomal recessive disorder characterized by massive birth weight, swollen globular body, generalized edema, short limbs, postaxial polydactyly, thick skin, facial dysmorphism (slanted palpebral fissures, hypertelorism, epicanthic folds, dysplastic ears), excessive connective tissue, renal dysplasia, and in some patients, organomegaly, craniosynostosis with acrocephaly, omphalocele, cleft palate, and cryptorchidism. Fewer than 10 cases have been reported to date.
Acquired hypertrichosis lanuginosa is a rare cutaneous paraneoplastic disease characterized by the presence of excessive lanugo-type hair on the glabrous skin of face, neck, trunk and limbs that can be associated with additional clinical features such as burning glossitis, papillary hypertrophy of the tongue, diarrhea, dysgeusia, and/or weight loss. It is associated with lymphoma or cancer of the gastrointestinal system, urinary tract, lung, breast, uterus or ovary.
Hypertrichosis lanuginosa congenita is a rare congenital skin disease characterized by the presence of 3 to 5cm long lanugo-type hair on the entire body, with the exception of palms, soles, and mucous membranes.
This syndrome is characterized by the association of hypogonadotropic hypogonadism and frontoparietal alopecia.
This syndrome is characterized by the association of severe nasal hypoplasia, hypoplasia of the eyes, hyposmia, hypogeusia and hypogonadotropic hypogonadism.
Sporadic infantile bilateral necrosis is the sporadic form of infantile bilateral striatal necrosis (IBSN; see this term), a syndrome of bilateral symmetric spongy degeneration of the caudate nucleaus, putamen and globus pallidus characterized by developmental regression, choreoathetosis and dystonia progressing to spastic quadriparesis.
Familial infantile bilateral striatal necrosis is the familial form of infantile bilateral striatal necrosis (IBSN; see this term), a syndrome of bilateral symmetric spongy degeneration of the caudate nucleaus, putamen and globus pallidus characterized by developmental regression, choreoathetosis and dystonia progressing to spastic quadriparesis.
Oligomeganephronia is a developmental anomaly of the kidneys, and the most severe form of renal hypoplasia (see this term), characterized by a reduction of 80% in nephron number and a marked hypertrophy of the glomeruli and tubules.
Hypothyroidism due to mutations in transcription factors involved in pituitary development or function is a type of central congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth, characterized by low levels of thyroid hormones caused by disorders in the development or function of the pituitary.
Hypotrichosis-intellectual disability, Lopes type is characterised by hypotrichosis, syndactyly, intellectual deficit and early eruption of teeth. It has been described in two patients. The mode of transmission appears to be autosomal recessive.
The Immunodeficiency, Centromeric region instability, Facial anomalies syndrome (ICF) is a rare autosomal recessive disease characterized by immunodeficiency, although B cells are present, and by characteristic rearrangements in the vicinity of the centromeres (the juxtacentromeric heterochromatin) of chromosomes 1 and 16 and sometimes 9.
Multiple system atrophy, cerebellar type (MSA-c) is a form of multiple system atrophy (MSA; see this term) with predominant cerebellar features (gait and limb ataxia, oculomotor dysfunction, and dysarthria).
Progressive sensorineural hearing loss - hypertrophic cardiomyopathy is an extremely rare disorder described in one family to date that is characterized by progressive, late onset, autosomal dominant sensorineural hearing loss, QT interval prolongation, and mild cardiac hypertrophy.
Hughes-Stovin syndrome (HSS) is a life-threatening disorder, believed to be a cardiovascular clinical variant manifestation of Behçet's disease (BD; see this term). It is characterized by the association of multiple pulmonary artery aneurysms (PAAs) and peripheral venous thrombosis.
, which is endemic to the Southwestern United States, Central America, South America and Mexico, and is acquired by inhalation of the infective arthroconidia, often found in soil. In most cases it is a benign, self-limiting febrile illness, but in a minority of cases it can become a potentially lethal infection of the lungs and, extremely rarely, spread to other organs (through hematogenous dissemination) with manifestations including meningitis, osteomyelitis, and skin and soft-tissue involvement.
Autosomal dominant Charcot-Marie-Tooth disease type 2M (CMT2M) is a form of axonal Charcot-Marie-Tooth disease, a peripheral motor and sensory neuropathy. CMT2M is characterized by congenital pstosis and early cataract associated to a mildly progressive peripheral neuropathy of variable onset from birth to the 6th decade, pes cavus, reduced to absent ankles tendon reflexes and sometimes neutropenia.
Heart-hand syndrome refers to a group of congenital disorders characterized by malformations of the upper limbs and heart. To date, heart-hand syndrome comprises the following rare syndromes; Holt-Oram syndrome; heart-hand syndrome type 2; heart-hand syndrome type 3; heart hand syndrome, Slovenian type, brachydactyly-long thumb; and patent ductus arteriosus-bicuspid aortic valve - hand anomalies (see these terms).
Dysmorphism-short stature-deafness-disorder of sex development syndrome is characterized by dysmorphism (including facial asymmetry, arched eyebrows, hypertelorism, broad and flat nasal bridge, microtia, small nose with anteverted nostrils, micrognathia), deafness, cleft palate, male pseudohermaphroditism, and growth and psychomotor retardation. It has been described in two siblings. It is transmitted as an autosomal recessive trait.
Cold autoimmune hemolytic anemia comprises two types of autoimmune hemolytic anemia (AIHA; see this term) defined by the presence of cold autoantibodies (autoantibodies which are active at temperatures below 30°C): cold agglutinin disease (CAD), which is the more common, and paroxysmal cold hemoglobinuria (PCH; see these terms).
Ptosis - upper ocular movement limitation - absence of lacrimal punctum is a recently described association of absence of the lower lid lacrimal punctum, bilateral ptosis, elevation deficiency of both eyes and mild facial dysmorphism.
The newly described 8q12 microduplication syndrome is associated with unusual and characteristic multi-organ clinical features, which include hearing loss, congenital heart defects, intellectual disability, hypotonia in infancy, and Duane anomaly (see this term).
Polyvalvular heart disease syndrome is a recently described syndrome characterized by the combination of polyvalvular heart disease, short stature, facial anomalies and intellectual deficit.
The newly described 5q35 microduplication syndrome is associated with microcephaly, short stature, developmental delay and delayed bone maturation.
Fused manidbular incisors is an extremely rare dental anomaly that is characterized by the union of two, normally separated, incisor tooth germs of the primary dentition. It is frequently associated with hypodontia (see this term) and an increased risk of pulp exposure.
Type A insulin-resistance syndrome belongs to the group of extreme insulin-resistance syndromes (which includes leprechaunism, the lipodystrophies, Rabson-Mendenhall syndrome and type B insulin resistance syndrome; see these terms) and is characterized by the triad of hyperinsulinemia, acanthosis nigricans (skin lesions associated with insulin resistance), and signs of hyperandrogenism in females without lipodystrophy and who are not overweight.
Isolated agammaglobulinemia (IA) is the non-syndromic form of agammaglobulinemia, a primary immunodeficiency disease, and is characterized by deficient gamma globulins and associated predisposition to frequent and recurrent infections from infancy.
Isotretinoin embryopathy is an association of malformations caused by the teratogenic effect of isotretinoin, an oral synthetic vitamin A derivative, which is used to treat severe recalcitrant cystic acne. Exposure to isotretinoin during the first trimester of pregnancy has been associated with an increased risk of spontaneous abortions and severe birth defects including serious craniofacial (microcephaly, asymmetric crying facies, microphthalmia, developmental abnormalities of the external ear, ocular hypertelorism), cardio vascular (conotruncal heart defects, aortic arch abnormalities), and central nervous system (hydrocephalus, microcephaly, lissencephaly, Dandy-Walker malformation, cognitive deficit) anomalies and thymic aplasia. Isoretinoin is contraindicated during pregnancy.
Ehlers-Danlos, vascular-like type is an adult-onset form of Ehlers-Danlos syndrome characterized by spontaneous dissection of medium-sized arteries during young adulthood, including mainly the iliac, femoral, and renal arteries.
Ehlers-Danlos/osteogenesis imperfecta syndrome is an association of the features of Ehlers-Danlos syndrome and osteogenesis imperfecta, characterized by generalized joint hypermobility and dislocations, skin hyperextensibility and/or translucency, and easy bruising as the predominant clinical features, while being invariably associated with mild signs of osteogenesis imperfecta, including short stature, blue sclera, and osteopenia or fractures.
Familial generalized lentiginosis is a rare, inherited, skin hyperpigmentation disorder characterized by widespread lentigines without associated noncutaneous abnormalities. Patients present multiple brown to dark brown, non-elevated macula of 0.2 to 1 cm in diameter, spread over the entire body, sometimes including palms or soles, but never oral mucosa.
Hemoglobin C - beta-thalassemia (HbC - BT) is a form of beta-thalassemia (see this term) resulting in moderate hemolytic anemia.
2000 IU/ml), recurring staphylococcal skin abscesses, and recurrent pneumonia with formation of pneumatoceles.
Hermansky-Pudlak syndrome with pulmonary fibrosis as a complication includes two types (HPS-1 and HPS-4) of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by oculocutaneous albinism, bleeding diathesis and, in some cases, pulmonary fibrosis or granulomatous colitis.
Hermansky-Pudlak syndrome without pulmonary fibrosis as a complication includes three relatively mild types (HPS-3, HPS-5 and HPS-6) of Hermansky-Pudlak syndrome (HPS; see this term), a multi-system disorder characterized by ocular or oculocutaneous albinism, bleeding diathesis and, in some cases, granulomatous colitis.
This term refers to a group of diseases characterized by alpha-thalassemia and an associated disorder. Three conditions are included in this group: alpha thalassemia - X-linked intellectual deficit (or ATR-X syndrome), alpha-thalassemia-intellectual deficit syndrome (or ATR-16 syndrome) and alpha-thalassemia-myelodysplastic disease (or ATMDS; see these terms).*
Kallmann syndrome with cardiopathy is characterised by hypogonadotropic hypogonadism associated with gonadotropin-releasing hormone (GnRH) deficiency, anosmia or hyposmia (with hypoplasia or aplasia of the olfactory bulbs) and complex congenital cardiac malformations (double-outlet right ventricle, dilated cardiomyopathy, right aortic arch). It represents a distinct clinical entity from Kallmann syndrome.
Isolated cloverleaf skull syndrome is a form of craniosynostosis involving multiple sutures (coronal, lambdoidal, sagittal and metopic ) characterized by a trilobular skull of varying severity (frontal towering and bossing, temporal bulging and a flat posterior skull), dysmorphic features (downslanting palpebral fissures, midface hypoplasia, and extreme proptosis) and that is complicated by hydrocephalus, cerebral venous hypertension, developmental delay/intellectual disability and hind brain herniation.
Angio-osteohypertrophic (AOH) syndrome is a congenital vascular bone syndrome (CVBS) characterized by the presence of a vascular malformation in a limb, mainly of the arteriovenous type, which results in overgrowth of the affected limb.
Limb body wall complex (LBWC) is characterized by severe multiple congenital anomalies in the fetus with exencephaly/encephalocele, thoraco- and/or abdominoschisis (anterior body wall defects) and limb defects, with or without facial clefts.
Sclerosing mesenteritis (SM) is a rare pathological disease causing inflammation of the adipose tissue of the small bowel mesentery and is commonly associated with abdominal pain, diarrhea, nausea, weight loss, bloating and loss of appetite. The two subforms include mesenteric panniculitis (where inflammation and fatty necrosis are dominant features) and retractile mesenteritis (where fibrosis and retraction dominate).
1q44 microdeletion syndrome is a newly described syndrome associated with facial dysmorphism, developmental delay, in particular of expressive speech, seizures and hypotonia.
Multiple symmetric lipomatosis (MSL) is a rare subcutaneous tissue disease characterized by growth of symmetric non-encapsulated masses of adipose tissue mostly around the face and neck with variable clinical repercussions (e.g. reduced neck mobility, compression of respiratory structures).
Classical progressive supranuclear palsy, also known as Richardson's syndrome, is the most common clinical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease characterized by postural instability, progressive rigidity, supranuclear gaze palsy and mild dementia.
PSP-parkinsonism (PSP-P) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease.
PSP-corticobasal syndrome (PSP-CBS) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease.
Patterson-Stevenson-Fontaine syndrome is a very rare variant of acrofacial dysostosis characterized by mandibulofacial dysostosis and limb anomalies.
Biliary atresia with splenic malformation syndrome (BASM) designates the association of biliary atresia (see this term) and splenic abnormalities (mainly polysplenia and less frequently asplenia, double spleen). Cardiac defect, situs inversus and a preduodenal portal vein can also be present. It represents the embryonal or syndromic form of biliary atresia. It affects newborns or infants and is characterized by jaundice, pale stools, dark urine, failure to thrive, hepatomegaly, coagulopathy, anemia and often palpable spleen.
Infantile mercury poisoning is a rare intoxication affecting children, most commonly characterized by erythema of the hands, feet and nose, edematous, painful, pink to red, desquamating fingers and toes, bluish, cold and wet extremities, excessive sweating, irritability, photophobia, muscle weakness, diffuse hypotonia, paresthesia, hypertension and tachycardia, due to elemental, organic or inorganic mercury exposure. Additional manifestations include alopecia, loss of appetite, excessive salivation with red and swollen gums, tooth and nail loss, and insomnia.
Acute neonatal citrullinemia type I is a severe form of citrullinemia type 1 (see this term) characterized biologically by hyperammonemia and clinically by progressive lethargy, poor feeding and vomiting, seizures and possible loss of consciousness, within one to a few days of birth, with variable signs of increased intracranial pressure. The condition can lead to significant neurologic deficits.
Adult-onset citrullinemia type I is a form of citrullinemia type I (see this term) characterized clinically by adult onset of symptoms including variable hyperammonemia and less striking neurological findings which may include intense headache, scotomas, migraine-like episodes, ataxia, slurred speech, lethargy and drowsiness. Serious increased intracranial pressure may occur.
Prenatal benign hypophosphatasia (PB-HPP) is a very rare form of hypophosphatasia (see this term) characterized by prenatal skeletal manifestations (limb shortening and bowing) that slowly resolve spontaneously and later develop into the milder infantile, childhood or adult forms of the disease.
Juvenile cataract - microcornea - renal glucosuria is an extremely rare autosomal dominant association reported in a single Swiss family and characterized clinically by juvenile cataract associated with bilateral microcornea, and renal glucosuria without other renal tubular defects.
Ménétrier disease (MD) is a rare premalignant hyperproliferative gastropathy characterized by massive overgrowth of foveolar cells in the gastric lining, resulting in large gastric folds, and manifesting with epigastric pain, nausea, vomiting, peripheral edema and, less commonly, anorexia and weight loss.
Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome is characterized by metaphyseal dysplasia associated with short stature and facial dysmorphism (a beaked nose, short philtrum, thin lips, maxillary hypoplasia, dystrophic yellowish teeth) and acral anomalies (short fifth metacarpals and/or short middle phalanges of fingers two and five). It has been described in several members spanning four generations of a French-Canadian family. The syndrome is likely to be transmitted as an autosomal dominant trait.
Logopenic progressive aphasia (lv-PPA) is a form of primary progressive aphasia (PPA; see this term), characterized by impaired single-word retrieval and naming and impaired repetition with spared single-word comprehension and object knowledge.
Autosomal dominant optic atrophy and peripheral neuropathy (ADOAPN) is a form of autosomal dominant optic atrophy (ADOA, see this term), characterized by progressive and isolated visual loss in the first decade of life, decreased reflexes in the lower limbs and a mild cerebellar stance.
gene, and like other dominantly inherited forms of the disease manifesting with opthalmological (myopia, retinal detachment and cataracts), orofacial (micrognathia, midface hypoplasia and cleft palate) auditory (sensorineural hearing loss) and articular (epiphyseal dysplasia) symptoms
2q31.1 microdeletion syndrome is a well-defined and clinically recognisable syndrome characterized by moderate to severe developmental delay, short stature, facial dysmorphism and variable limb defects.
6p22 microdeletion syndrome is a newly described syndrome associated with a variable clinical phenotype including developmental delay, facial dysmorphism, short neck and diverse malformations.
8p11.2 deletion syndrome is a contiguous gene syndrome characterized by the association of congenital spherocytosis, dysmorphic features, growth delay and hypogonadotropic hypogonadism.
Junctional epidermolysis bullosa, localized non-Herlitz-type is a form of non-Herlitz junctional epidermolysis bullosa (JEB-nH, see this term) characterized by localized blistering, and dystrophic or absent nails.
46,XY partial gonadal dysgenesis (46,XY PGD) is a disorder of sex development (DSD) associated with anomalies in gonadal development that results in genital ambiguity of variable degree ranging from almost female phenotype to almost male phenotype in a patient carrying a male 46,XY karyotype.
Pineal parenchymal tumor of intermediate differentiation (PPTID) describes a rare type of pineal parenchymal tumor (PPT) of intermediate-grade malignancy manifesting with visual disturbances, headaches, loss of coordination and balance, nausea and vomiting due to obstructive hydrocephalus, and that is classified as either grade II PPTID or grade III PPTID according to the degree of neuronal differentiation and mitotic activity.
Extraventricular neurocytoma (EVN), a variant of central neurocytoma (see this term), is a rare neuronal neoplasm, composed of round cells with neuronal differentiation, which is located outside of the ventricular system, usually within the spinal cord or cerebral hemispheres and that manifests with headache, nausea, vomiting, complex partial seizures or focal neurological deficits. In some cases it may exhibit atypical features consistent with aggressive clinical behavior.
Microcephaly-microcornea syndrome, Seemanova type is characterised by microcephaly and brachycephaly, eye anomalies (microphthalmia, microcornea, congenital cataract), hypogenitalism, severe intellectual deficit, growth retardation and progressive spasticity. It has been described in two patients (a male and his sister's son). Both patients also presented with facial dysmorphism, including upslanting palpebral fissures, epicanthal folds, highly arched palate, microstomia, and retrognathia. This syndrome is transmitted as an X-linked trait.
Anophthalmia and microphthalmia describe, respectively, the absence of an eye and the presence of a small eye within the orbit.
19p13.12 microdeletion syndrome is a newly described syndrome characterized by moderate to severe developmental delay, language delay, bilateral sensorineural and/or conductive hearing loss and facial dysmorphism.
Maternally-inherited mitochondrial dystonia is a rare neurological mitochondrial DNA-related disorder characterized clinically by progressive pediatric-onset dystonia with variable degrees of severity.
Renal tubulopathy - encephalopathy - liver failure describes a spectrum of phenotypes with manifestations similar but milder than those seen in GRACILE syndrome (see this term) and that can be associated with encephalopathy and psychiatric disorders.
Mikati-Najjar-Sahli syndrome is characterized by microcephaly, hypergonadotropic hypogonadism, short stature and facial dysmorphism (a narrow forehead, hypertrophy and fusion of the eyebrows, micrognathia and pinnae abnormalities).
Early onset torsion dystonia (EOTD) is a rare movement disorder characterized by involuntary, repetitive, sustained muscle contractions or postures involving one or more sites of the body.
Congenital autosomal recessive sideroblastic anemia (ARSA) is a non-syndromic, microcytic/hypochromic sideroblastic anemia, present from early infancy and characterized by severe microcytic anemia, which is not pyridoxine responsive, and increased serum ferritin.
Familial visceral myopathy is a rare hereditary myopathic degeneration of both gastrointestinal and urinary tracts that causes chronic intestinal pseudo-obstruction. It usually presents after the first decade of life with megaduodenum, megacystis and symptoms such as abdominal distension and/or pain, vomiting, constipation, diarrhea, dysphagia, and/or urinary tract infections.n.
14q12 microdeletion syndrome is a recently described syndrome characterized by severe intellectual deficit, with a normal neonatal period, followed by a phase of regression at the age of 3-6 months.
The proximal 16p11.2 microdeletion syndrome is a chromosomal anomaly characterized by developmental and language delays, mild intellectual disability, social impairments (autism spectrum disorders), mild variable dysmorphism and predisposition to obesity.
16p11.2p12.2 microduplication syndrome is a rare chromosomal anomaly syndrome resulting from the partial duplication of the short arm of chromosome 16 with a highly variable phenotype typically characterized by developmental/psychomotor delay (particularly of speech), intellectual disability, autism spectrum disorder and/or obsessive and repetitive behaviour, behavioural problems (such as aggression and outbursts), dysmorphic facial features (triangular face, deep set eyes, broad and prominent nasal bridge, upslanting or narrow palpebral features, hypertelorism). Additionally, finger/hand anomalies, short stature, microcephaly and slender build are frequently described.
16p13.11 microdeletion syndrome is a recently described syndrome characterized by developmental delay, microcephaly, epilepsy, short stature, facial dysmorphism and behavioral problems.
16p13.11 microduplication syndrome is a recently described syndrome associated with variable clinical features including behavioral abnormalities, developmental delay, congenital heart defects and skeletal anomalies.
16q24.3 microdeletion syndrome is a recently described syndrome associated with variable developmental delay, facial dysmorphism, seizures and autistic spectrum disorder.
20p12.3 microdeletion syndrome is a recently described syndrome characterized by Wolff-Parkinson-White syndrome (see this term), variable developmental delay and facial dysmorphism.
Paternal 20q13.2q13.3 microdeletion syndrome is a recently described syndrome characterized by severe pre- and post-natal growth retardation, microcephaly, intractable feeding difficulties, mild psychomotor retardation, hypotonia and facial dysmorphism.
20q13.33 is a rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 20 with a highly variable phenotype typically characterized by hypotonia, intellectual disability, cognitive and language deficits (including decreased or absent speech), pre and post-natal growth retardation, feeding difficulties, microcephaly, and malformed hands and feet. Neurodevelopmental disorders (including hyperactivity, social interactive problems and autism spectrum disorder), seizures and dysmorphic facial features (high forehead, hypertelorism, malformed ears, broad nasal bridge, bulbous nasal tip, thin upper lip, small chin) are frequently associated.
Trisomy 20p is a chromosomal disorder resulting from duplication of all or part of the short arm of chromosome 20. It is mostly characterized by normal growth, mild to moderate intellectual disability, speech delay, poor coordination and evocative facial features.
Atypical Norrie disease due to monosomy Xp11.3 is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the short arm of chromosome X, principally characterized by classical Norrie disease (bilateral, severe retinal malformations and opacity of the lens leading to congenital blindness, on occasion associated with progressive sensorineural deafness and intellectual disability), microcephaly, hypotonia, psychomotor and growth delay, moderate to severe mental handicap and disruptive behaviour. Clinical phenotype is highly variable and immunodeficiency, epilepsy and hypogonadism have also been reported.
Nevus of Ito is a benign dermal melanocytosis occurring most frequently in the Asian populations and characterized by unilateral, asymptomatic, blue, gray or brown skin pigmentation within the acromioclavicular and upper chest area (involving the side of the neck, the supraclavicular and scapular areas, and the shoulder region). It is usually diagnosed in early infancy and in early adolescence. Nevus of Ito may progressively enlarge and darken in color (particularly with puberty) and its appearance usually remains stable once adulthood is reached. Spontaneous regression does not occur. Malignant melanoma has rarely been reported within a nevus of Ito. It shares the clinical features of nevus of Ota (see this term), except its anatomic location and may in rare occasions occur together with the latter.
Generalized peeling skin syndrome (PSS) is a form of PSS (see this term) presenting with a generalized distribution. It comprises two sub-types: the non-inflammatory (PSS type A) and the inflammatory (PSS type B) form (see these terms). PSS type A is characterized by generalized white scaling with superficial peeling of the skin, while PSS type B is characterized by superficial patchy peeling of the entire skin with underlying erythroderma, associated with pruritus, and atopy.
Peeling skin syndrome (PSS) type B, also known as peeling skin disease (PSD), is a rare inflammatory form of ichthyosis (see this term) characterized by superficial patchy peeling of the entire skin with underlying erythroderma, pruritus, and atopy.
Microcephalic osteodysplastic primordial dwarfism (MOPD) types 1 and 3 are characterized by intrauterine and postnatal growth retardation, microcephaly, facial dysmorphism, skeletal dysplasia, low-birth weight and brain anomalies. Although MOPD types 1 and 3 were originally described as two separate entities on the basis of radiological criteria (notably small differences in pelvic and long bone structure), later reports confirmed that the two forms represent different modes of expression of the same syndrome.
Familial multiple meningioma is a rare, benign neoplasm of the central nervous system characterized by the development of multiple or, rarely, solitary meningiomas in two or more blood relatives, without other apparent syndromic manifestations. Depending on the localization, growth rate and size of the tumors, patients can present with subtle, gradually worsening or abrupt and severe neurological compromise or can be completely asymptomatic.
Natural killer (NK)-cell enteropathy is a benign NK-cell lymphoproliferative disease characterized by minor abdominal symptoms (abdominal pain, diverticulosis, constipation and reflux) due to NK cell-derived lesions in the mucosal layer of the gastrointestinal tract and often mistaken for NK or T-cell lymphoma (see these terms).
Osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome is characterized by severe dwarfism, progressive scoliosis and bilateral dislocation of the hip, associated with sensorineural deafness and retinitis pigmentosa. Radiographs show diffuse osteoporosis, severe bone-age delay and dysplasia of the femoral head. It has been described in two patients. Transmission is autosomal dominant variable penetrance.
Neuroectodermal-endocrine syndrome is characterised by a combination of endocrine and neuroectodermal abnormalities, including low growth hormone levels, delayed puberty, type II diabetes mellitus, mild intellectual deficit, sensorineural deafness, characteristic facial appearance and alopecia. It has been described in four sibs from Myanmar.
Intraocular medulloepithelioma is a rare eye tumor characterized by a white, gray or yellow-colored cystic mass that arises from the primitive neuroectodermal, nonpigmented epithelium of the ciliary body, or occasionally from the optic nerve, optic disc, retina or iris. Typically it has a benign clinical course with good prognosis and generally presents with childhood onset of poor vision and pain, glaucoma, and/or cataract. Leukocoria, exotropia, exophthalmos, strabismus, epiphora, change in eye color, hyphema, and raised intraocular pressure are also remarkable manifestations.
Posterior meningocele is a rare neural tube closure defect characterized by the herniation of a cerebrospinal fluid-filled sac, that is lined by dura and arachnoid mater, through a posterior spina bifida and covered by a layer of skin of variable thickness, which may be dysplastic or ulcerated. The spinal cord and nerves are generally not included and function normally, although sometimes a tethered cord may be associated. They are most commonly located in the lumbar or sacral region.
Unilateral focal polymicrogyria (BFPP) is the mildest sub-type of polymicrogyria (PMG; see this term), a cerebral cortical malformation characterized by excessive cortical folding and abnormal cortical layering, that affects only one small region of the brain and that may show no neurologic involvement.
Neutropenia-monocytopenia-deafness syndrome is characterised by neutropenia with myeloid marrow hypoplasia, monocytopenia, and congenital deafness. It has been described in three siblings who suffered recurrent bacterial infections.
Odonto-onycho dysplasia-alopecia syndrome is a rare, genetic ectodermal dysplasia syndrome characterized by almost total alopecia with only sparse, thin, brittle, slow-growing scalp hair, fair and sparse eyebrows and eyelashes, absent axillary and pubic hair, fragile and brittle fingernails, thick and brittle toenails (both with a subungual corneal layer), hypodontia, microdontia, widely spaced teeth with hypoplastic enamel, mild palmoplantar keratosis, café-au-lait spots and areolae anomalies. There have been no further descriptions in the literature since 1985.
Olivopontocerebellar atrophy-deafness syndrome is characterised by infancy-onset olivopontocerebellar atrophy, sensorineural deafness and speech impairment. It has been described in less than 15 children. Most cases were sporadic, but autosomal recessive inheritance was suggested in three cases.
, transmitted by the black fly. The infection can either be asymptomatic or manifest as an ocular disease (river blindness) with itchy eyes, erythema, photophobia, onchodermatitis or onchocercal skin disease (classified into acute papular, chronic papular, lichenified, atrophic, and depigmentated) and onchocercomas (over bony prominences). Other classic clinical manifestations are ichthyosis-like lesions (''lizard skin'') and ''hanging groin'', which may be associated with lymphadenopathy.
Opitz G/BBB syndrome (OS) is a multiple congenital anomalies disorder characterized by malformations of the midline including hypertelorism, laryngo-tracheo-esophalgeal defects and hypospadias. There are two clinically indistinguishable genetic subtypes of Opitz G/BBB: X-linked Opitz G/BBB syndrome (XLOS), and autosomal dominant Opitz G/BBB syndrome (ADOS) (see these terms).
Oromandibular-limb hypogenesis syndromes (OLHS) are a group of dysmorphic complexes (including Charlie M syndrome, Hanhart syndrome and glossopalatine ankylosis; see these terms) characterized by the association of severe asymmetric limb defects (primarily involving distal segments) and abnormalities of the oral cavity and mandible (hypoglossia, aglossia, micrognathia, glossopalatine ankylosis, cleft palate, and gingival anomalies).
Idiopathic pulmonary arterial hypertension (IPAH) is a sporadic form of pulmonary arterial hypertension (PAH, see this term) characterized by elevated pulmonary arterial resistance leading to right heart failure. IPAH is progressive and potentially fatal and not associated with an underlying condition or family history of PAH.
Heritable pulmonary arterial hypertension (HPAH) is a form of pulmonary arterial hypertension (PAH, see this term), occurring due to mutations in PAH predisposing genes or in a familial context. HPAH is characterized by elevated pulmonary arterial resistance leading to right heart failure. HPAH is progressive and potentially fatal.
Pulmonary arterial hypertension associated with another disease is a group of conditions that lead to PAH (see this term); connective tissue diseases (lupus erythematosus, systemic sclerosis and mixed connective tissues disease), congenital heart disease (Eisenmenger syndrome), HIV infection, portal hypertension, schistosomiasis and chronic hemolytic anemia (see these terms),which is characterized by elevated pulmonary arterial resistance leading to right heart failure that is progressive and potentially fatal.
Pulmonary arterial hypertension (PAH, see this term) associated with connective tissue disease (PAH-CTD) is a form of pulmonary arterial hypertension (PAH, see this term) characterized by an elevated pulmonary arterial resistance leading to right heart failure observed as a complication of a connective tissue disease.
Behavioral variant of frontotemporal dementia (bv-FTD) is a form of frontotemporal dementia (FTD; see this term), characterized by progressive behavioral impairment and a decline in executive function with frontal lobe-predominant atrophy.
Multiple endocrine neoplasia (MEN) is a group of rare inherited cancer syndromes characterized by the development of two or more endocrine gland tumors, sometimes with tumor development in other tissues or organs.
Spinocerebellar ataxia type 35 (SCA35) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by the adult-onset of progressive gait and limb ataxia, dysarthria, ocular dysmetria, intention tremor, hyperreflexia and spasmodic torticollis.
HyHyperinsulism due to UCP2 deficiency (HIUCP2) is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI, see this term) characterized by hypoglycemic episodes from the neonatal period, a good clinical response to diazoxide and a probable transient nature of the disease with spontaneous resolution.
Autosomal dominant hyperinsulinism due to SUR1 deficiency is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI), characterized by hypoglycemic epiosodes that are usually mild, escaping detection during infancy and usually a good clinical response to diazoxide. Autosomal dominant hyperinsulinism due to SUR1 deficiency usually has a milder phenotype when compared to that resulting from recessive K-ATP mutations (recessive forms of Diazoxide-resistant hyperinsulinism, see this term).
Autosomal dominant hyperinsulinism due to Kir6.2 deficiency is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI) characterized by hypoglycemic epiosodes that are usually mild, escaping detection during infancy, and usually a good clinical response to diazoxide, (but some are diazoxide resistant). Autosomal dominant hyperinsulinism due to Kir6.2 deficiency usually has a milder phenotype when compared to that resulting from recessive K+ (K-ATP) channel mutations (Recessive forms of diazoxide-resistant hyperinsulinism, see this term).
Osteogenesis imperfecta-retinopathy-seizures-intellectual disability syndrome is characterized by osteogenesis imperfecta, wormian bones, optic atrophy, retinopathy, seizures and severe developmental delay. It has been described in two sibs born to consanguineous parents.
Osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome is characterised by osteoporosis, macrocephalus, brachytelephalangy, and hyperextensibility of the joints. Congenital amaurosis and intellectual deficit have also been reported. This syndrome has been described in three members of one family.
with prominent pachydermia and minimal-to-absent skeletal changes.
Toxic maculopathy due to antimalarial drugs is a rare, acquired eye disease, due to long-term exposure to chloroquinine (CQ) or hydrochloroquinine (HCQ), characterized by a slowly progressive, usually non-reversible, development of bilateral atrophic bull's-eye maculopathy (progressive loss of central vision acuity, reduced color vision and central scotoma), which in severe cases can spread over the entire fundus, leading to widespread retinal atrophy and visual loss.
Calciphylaxis cutis is a life-threatening syndrome characterized by progressive and painful skin ulcerations associated with media calcification of medium-size and small cutaneous arterial vessels. It affects mainly patients on dialysis or after renal transplantation.
Septopreoptic holoprosencephaly (HPE) is a very rare subtype of lobar HPE (see this term) characterized by midline fusion limited to the septal and/or preoptic regions of the telencephalon without a significant frontal neocortical fusion.
Microform holoprosencephaly is a benign form of holoprosencephaly (HPE; see this term) characterized by midline defects without the typical HPE defect in brain cleavage.
Laryngo-tracheo-esophageal cleft (LC) type 0 is a congenital respiratory tract anomaly characterized by a submucosal laryngo-tracheo-esophageal cleft with minor symptoms or an asymptomatic course.
The connatal form of Pelizaeus-Merzbacher disease (PMD) is the most severe form of PMD (see this term).
The null syndrome is part of the Pelizaeus-Merzbacher disease (PMD; see this term) spectrum and is characterized by mild PMD features associated with demyelinating peripheral neuropathy.
Pelizaeus-Merzbacher like disease (PMLD) is an autosomal recessive leukodystrophy sharing identical clinical and radiological features as X-linked Pelizaeus-Merzbacher disease (PMD; see this term).
60 years) and presenting with abdominal pain, steatorrhea, obstructive jaundice and other organ (bile duct, kidneys and retroperitoneum) involvement. It is thought to be due to an immunoglobulin G4 (IgG4)-associated systemic disease.
60 years) and presenting with abdominal pain, steatorrhea and obstructive jaundice.
. Patients present with a prolonged, atypical course (absence of myoclonus or ataxia) unlike other forms of prion disease with severe neurofibrillary tangle pathology and high levels of cerebral amyloidosis.
Cutaneous collagenous vasculopathy (CCV) is a primary microangiopathy confined to the skin, characterized by multiple and widespread telangiectasias.
Bullous diffuse cutaneous mastocytosis (BDCM) is a form of diffuse cutaneous mastocytosis (DCM; see this term) characterized by generalized erythroderma and severe blistering associated with the accumulation of mast cells in the skin.
Pseudoxanthomatous diffuse cutaneous mastocytosis (PDCM) is a rare form of diffuse cutaneous mastocytosis (DCM; see this term) characterized by yellow-orange infiltrated and xanthogranuloma-like lesions with only limited blistering.
Syndromic recessive X-linked ichthyosis (RXLI) refers to the cases of RXLI (see this term) that are associated with extracutaneous manifestations as part of a syndrome.
Inherited or familial Creutzfeldt-Jakob disease (fCJD) is a very rare form of genetic prion disease (see this term) characterized by typical CJD features (rapidly progressive dementia, personality/behavioral changes, psychiatric disorders, myoclonus, and ataxia) with a genetic cause and sometimes a family history of dementia.
Young-onset Parkinson disease (YOPD) is a form of Parkinson disease (PD), characterized by an age of onset between 21-45 years, rigidity, painful cramps followed by tremor, bradykinesia, dystonia, gait complaints and falls, and other non-motor symptoms. A slow disease progression and a more pronounced response to dopaminergic therapy are also observed in most YOPD forms.
. AE is characterized by an initial asymptomatic incubation period of many years followed by a chronic course where the clinical manifestations include epigastric pain and jaundice.
Well-differentiated fetal adenocarcinoma (WDFA) of the lung is a rare, primary, low-grade, bronchopulmonary neoplasm characterized by a well-circumscribed, usually large, pulmonary mass that is histologically composed of glycogen-rich neoplastic glands and tubules that resemble fetal lungs at 10 to 16 weeks of gestation and benign adjacent stroma. It typically presents with chest pain, cough, dyspnea, hemoptysis and/or generalized, non-specific symptoms, such as night sweats, lethargy, poor appetite and weight loss.
Small cell carcinoma of the bladder (SCCB) is a very rare, poorly differentiated neuroendocrine epithelial bladder tumor characterized clinically by hematuria and/or dysuria and a highly aggressive course.
Infantile glycerol kinase deficiency (GKD) is a severe form of GKD (see this term) characterized clinically by poor feeding, failure to thrive, salt-wasting dehydration, vomiting, Addisonian pigmentation, hypotonia, and disorders of consciousness. Some patients have complex GKD associated with adrenal hypoplasia congenita and/or Duchenne muscular dystrophy (DMD) (see these terms) with manifestations including intellectual deficit, dysmorphic facial features, abnormal external genitalia, strabismus, seizures, and progressive lethargy.
Juvenile glycerol kinase deficiency (GKD) is an uncommon form of GKD (see this term) characterized by Reye-like clinical manifestations including episodic vomiting, acidemia, and disorders of consciousness.
Adult glycerol kinase deficiency (GKD) is an uncommon form of GKD (see this term) diagnosed fortuitously and characterized by pseudohypertriglyceridemia in otherwise healthy adults.
Short stature-deafness-neutrophil dysfunction-dysmorphism syndrome is characterised by short stature, sensorineural deafness, mutism, facial dysmorphism and abnormal neutrophil chemotaxis (leading to recurrent infections).
Autosomal recessive hypophosphatemic rickets (ARHR) is a hereditary renal phosphate-wasting disorder characterized by hypophosphatemia, rickets and/or osteomalacia and slow growth.
infections, thought to be a result of HTLV-1-induced immunosuppression. Lymphadenopathy, anemia, mild to moderate pruritus and increased incidence of other infections (e.g. crusted scabies) have also been reported in some patients. Patients may subsequently develop other HTLV-1 associated conditions such as adult T-cell leukemia/lymphoma and tropical spastic paraparesis (see these terms).
Primary non-gestational choriocarcinoma of ovary is a rare ovarian germ cell malignant tumor (see this term), arising from primordial germ cells, usually presenting with nausea, vomiting, abdominal pain, menstrual irregularities, and characterized by fast growth pattern, metastasis to lung, liver and brain and production of human chorionic gonadotrophin (hCG). It is apparently chemoresistant and has a worse prognosis than gestational choriocarcinoma (see this term) and hence should be distinguished from the latter by DNA polymorphism.
12q15q21.1 microdeletion syndrome is a rare chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 12, with a highly variable phenotype, typically characterized by developmental delay, learning disability, intra-uterine and postnatal growth retardation, and mild facial dysmorphism that changes with age. Nasal speech and hypothyroidism are also associated.
Neonatal glycine encephalopathy is a frequent, usually severe form of glycine encephalopathy (GE; see this term) characterized by coma, apnea, hypotonia, seizure and myoclonic jerks in the neonatal period, and subsequent developmental delay.
Infantile glycine encephalopathy is a mild to severe form of glycine encephalopathy (GE; see this term), characterized by early hypotonia, developmental delay and seizures.
Vitamin B12-unresponsive methylmalonic acidemia type mut0 is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.
Idiopathic chronic eosinophilic pneumonia (ICEP) is a very rare, severe, interstitial lung disease of insidious onset with subacute or chronic non-specific respiratory manifestations (dyspnea, cough, wheezing) often associated with systemic manifestations (fatigue, malaise, weight loss).
POEMS syndrome is a paraneoplastic syndrome characterized by polyradiculoneuropathy (P), organomegaly (O), endocrinopathy (E), clonal plasma cell disorder (M), and skin changes (S). Other features include papilledema, extravascular volume overload, sclerotic bone lesions, thrombocytosis/erythrocytosis, and elevated VEGF levels.
Fetal varicella syndrome (CVS) is an acquired developmental anomaly syndrome characterized by skin, neurological, ocular, limbs and growth defects secondary to maternal Varicella-Zoster Virus (VZV) infection.
Reactive arthritis (ReA) is an autoimmune disorder belonging to the group of seronegative spondyloarthropathies and is characterized by the classic triad of arthritis, urethritis and conjunctivitis.
Congenital herpes virus infection is a group of anomalies that an infant may present as a result of maternal infection and subsequent foetal infection with herpes virus. This virus causes recurrent cutaneous infections in adults, often involving the lips or the genitalia. Herpes infections in other organs, such as the liver or central nervous system, are less frequent.
Tetrahydrobiopterin-responsive hyperphenylalaninemia/ phenylketonuria (BH4-responsive hyperphenylalaninemia/ phenylketonuria) is a form of phenylketonuria (PKU, see this term), an inborn error of amino acid metabolism, characterized by mild to moderate symptoms of PKU including impaired cognitive function, seizures, and behavioral and developmental disorders, and a marked reduction and normalization of elevated phenylalanine concentrations after oral loading with tetrahydrobiopterin (BH4; sapropterin dihydrochloride), an essential cofactor of phenylalanine hydroxylase.
Grayson-Wilbrandt corneal dystrophy (GWCD) is an extremely rare form of corneal dystrophy characterized by variable patterns of opacification in the Bowman layer of the cornea which extend anteriorly into the epithelium with decreased to normal visual acuity.
Right temporal lobar atrophy (RTLA) is an anatomic variant of frontotemporal dementia (FTD), characterized by behavioral dysfunction, personality changes, episodic memory loss, and prosopagnosia; attributable to an asymmetrical predominantly right-sided, frontotemporal atrophy.
1p21.3 microdeletion syndrome is an extremely rare chromosomal anomaly characterized by severe speech and language delay, intellectual deficiency, autism spectrum disorder(see this term).
Chronic intestinal failure (CIF) is a chronic type of intestinal failure characterized by a nonfunctioning small bowel (that may be reversible or irreversal) where the body is unable to maintain energy and nutritional needs through absorption of food or nutrients via the intestinal tract (despite being metabolically stable) and which therefore necessitates long-term parenteral feeding. CIF may be the result of congenital digestive diseases (such as gastroschisis, atresia of small intestine; see these terms), short bowel syndrome (see this term), intra-abdominal or pelvic cancer, or progressive and devastating gastrointestinal or systemic benign diseases (such as Crohn disease; see this term).
Congenital absence/hypoplasia of thumb is a rare developmental defect during embryogenesis characterized by underdevelopment of the thumb, ranging from a slight decrease in thumb size to complete absence of the thumb. The malformation may occur isolated, combined to other defects of the hand or upper limb, or as part of a multiple congenital anomaly syndrome.
Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a hand-foot malformation characterized by triphalangeal thumbs and pre- and postaxial polydactyly, isolated syndactyly or complex polysyndactyly.
Tibio-fibular synostosis is a rare, non-syndromic limb malformation characterized by fusion of the proximal or distal tibial and fibular metaphysis and/or diaphysis, frequently associated with distal positioning of the proximal tibiofibular joint, leg length discrepancy, bowing of the fibula, and valgus deformity of the knee.
Congenital absence of both forearm and hand, unilateral is a rare developmental defect during embryogenesis characterized by a unilateral, transverse absence of the radius and ulna (of varying terminal lengths), as well as all the elements composing the hand. Left or right side may be involved.
Congenital absence of both forearm and hand, bilateral is a rare developmental defect during embryogenesis characterized by a bilateral, transverse absence of the radius and ulna (of varying terminal lengths), as well as all the elements composing the hand.
Congenital absence/hypoplasia of thumb, unilateral is a rare developmental defect during embryogenesis characterized by the unilateral underdevelopment of the thumb, ranging from a slight decrease in thumb size to complete absence of the thumb.
Congenital absence/hypoplasia of thumb, bilateral is a rare developmental defect during embryogenesis characterized by bilateral underdevelopment of the thumbs, ranging from a slight decrease in thumb size to complete absence of the thumbs. This anomaly counts for 20-60% of thumb hypoplasias.
Ehlers-Danlos syndrome, musculocontractural type is a congenital form of Ehlers-Danlos syndrome characterized by distinct craniofacial features, multiple contractures, progressive joint and skin laxity, adduction-flexion contractures of the thumbs, talipes equinovarus, bruisability and multisystem fragility-related manifestations.
Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency characterized by defects in the leukocyte adhesion process, marked leukocytosis and recurrent infections.
46,XX disorder of sex development-anorectal anomalies syndrome is a rare developmental defect during embryogenesis syndrome characterized by a normal female karyotype, normal ovaries, male or ambiguous genitalia, urinary tract malformations (ranging from bilateral renal agenesis to mild unilateral hydronephrosis), müllerian duct anomalies (e.g. complete absence of the uterus and vagina, bicornuate uterus), and imperforate anus. Additional features may include tracheoesophageal fistula, radial aplasia, and malrotation of the gut.
Mirror polydactyly-vertebral segmentation-limbs defects syndrome is characterised by mirror polydactyly, vertebral hypersegmentation and severe congenital limb deficiencies. Duodenal atresia and absent thymus were also reported. So far, it has been described in four unrelated infants identified through a congenital malformation screening program carried out in Spain. The prevalence was estimated at around 1 in 330,000. The etiology is unknown but it was suggested that the syndrome is caused by defective expression of a developmental control gene.
Primary cutaneous anaplastic large cell lymphoma (C-ALCL) is a rare T-cell non-Hodgkin lymphoma that affects the skin and generally shows no extracutaneous involvement at presentation. It belongs to the spectrum of primary cutaneous CD30+ lymphoproliferative disorders along with lymphomatoid papulosis (see this term) with which it shares overlapping clinical and histopathologic features.
ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is a type of ALCL (see this term), a rare and aggressive peripheral T-cell non-Hodgkin lymphoma affecting lymph nodes and extranodal sites, which is characterized by the expression of a protein called anaplastic lymphoma kinase (ALK).
Ependymal tumor is a tumor of neurectodermal origin arising from ependymal cells that line the ventricles and central canal of the spinal cord, that can occur in both children and adults, and that is characterized by wide a range of clinical manifestations depending on the location of the tumor, such as intracranial hypertension for tumors originating in the posterior fossa, behavioural changes and pyramidal signs for supratentorial tumors, and dysesthesia for tumors of the spinal cord. They can be classified as myxopapillary ependymoma, subependymoma, ependymoma (benign or low grade tumors) or anaplastic ependymoma (malignant or grade III tumors).
Benign familial infantile epilepsy (BFIE) is a genetic epileptic syndrome characterized by the occurrence of afebrile repeated seizures in healthy infants, between the third and eighth month of life.
Familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by renal magnesium (Mg) and calcium (Ca) wasting, nephrocalcinosis, kidney failure and, in some cases, severe ocular impairment. Two subtypes of FHHNC are described: FHHNC with severe ocular involvement (FHHNCOI) and without severe ocular involvement (FHHN) (see these terms).
Congenital hereditary facial paralysis-variable hearing loss syndrome is an extremely rare autosomal recessive disorder characterized by bilateral facial palsy with masked facies, sensorineural hearing loss, dysmorphic features (midfacial retrusion, low-set ears), and strabismus.
Hemidystonia-hemiatrophy (HD-HA) is a rare dystonia, usually caused by a static cerebral injury occurring at birth or during infancy, that is characterized by a combination of hemidystonia (HD), involving one half of the body, and hemiatrophy (HA) on the same side as the HD.
Glycogen storage disease due to acid maltase deficiency, infantile onset is the most severe form of glycogen storage disease due to acid maltase deficiency, characterized by cardiomegaly with respiratory distress, muscle weakness and feeding difficulties. It is often fatal.
Hereditary central diabetes insipidus is a rare genetic subtype of central diabetes insipidus (CDI, see this term) characterized by polyuria and polydipsia due to a deficiency in vasopressin (AVP) synthesis.
Robinow-like syndrome is characterized by the association of the clinical features present in Robinow syndrome (see this term; short stature, mesomelic brachymelia, macrocephaly, and hypoplastic genitalia), with anterior chamber cleavage anomalies. It has been described in two sisters and is transmitted as an autosomal recessive trait.
Autosomal dominant Robinow syndrome (DRS) is the more common type of Robinow syndrome (RS, see this term) characterized by mild to moderate limb shortening and abnormalities of the head, face and external genitalia.
Alpha-N-acetylgalactosaminidase (NAGA) deficiency is a very rare lysosomal storage disease that is clinically and pathologically heterogeneous and is characterized by deficient NAGA activity.
Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a rare form of gastric carcinoma (seen in approximately 10% of cases) with a male predominance, characterized by a latent EBV infection in gastric carcinoma cells, diffuse-type histology, a proximal location (in the body and cardia of the stomach) and a relatively favorable prognosis.
Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN) is a polymorphic disorder and a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by ataxia, sensorineural deafness and narcolepsy with cataplexy and dementia.
10cm) are often associated with pleural effusion and ascytes (the Meig's syndrome triad).
#946;2M) leading to progressive gastrointestinal dysfunction, Sjögren syndrome (see this term) and autonomic neuropathy.
Primary systemic amyloidosis (PSA) is a form of AL amyloidosis (see this term) caused by the aggregation and deposition of insoluble amyloid fibrils derived from misfolded monoclonal immunoglobulin light chains usually produced by a plasma cell tumor (see this term) and characterized by multiple organ involvement.
Primary localized amyloidosis is a form of AL amyloidosis (see this term) caused by the aggregation of insoluble amyloid fibrils derived from misfolded monoclonal immunoglobulin light chains usually produced by a plasma cell tumor (see this term) and characterized by localized amyloid deposition with clinical manifestations restricted to the organ involved, most frequently urinary tract (bladder), eye, respiratory tract (larynx, lungs), and skin.
Malignant peripheral nerve sheath tumor (MPNST) is a rare and often aggressive soft tissue sarcoma occurring in a wide range of anatomical sites.
Autosomal dominant proximal renal tubular acidosis (AD pRTA) is a form of proximal renal tubular acidosis (pRTA; see this term) characterized by an isolated defect in the proximal tubule leading to the decreased reabsorption of bicarbonate and consequently causing urinary bicarbonate wastage. Mild growth retardation and reduced bone density are extra-renal complications.
Severe Canavan disease (CD) is a rapidly progressing neurodegenerative disorder characterized by leukodystrophy with macrocephaly, severe developmental delay and hypotonia.
Erythrokeratoderma 'en cocardes' is a rare genodermatosis characterised by circumscribed target-like (or 'en cocardes') erythematous hyperkeratotic lesions. These lesions, which remit and recur, affect the trunk and extremities and are accompanied by scaly plaques evocative of erythrokeratoderma variabilis (see this term). Onset usually occurs at birth or during early childhood. Only few cases have been described. Transmission is autosomal dominant.
Multiple sclerosis-ichthyosis-factor VIII deficiency syndrome is characterized by the association of multiple sclerosis with lamellar ichthyosis (see this term) and hematological anomalies (beta thalassemia minor and a quantitative deficit of factor VIII-von Willebrand complex). Other clinical manifestations may include eye involvement (optic atrophy, diplopia), neuromuscular involvement (ataxia, pyramidal syndrome, gait disturbance) and sensory disorder. There have been no further descriptions in the literature since 1992.
The salt wasting form of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (classical 21 OHD CAH; see this term) is characterized by virilization of the external genitalia in females, hypocortisolism, precocious pseudopuberty and renal salt loss due to aldosterone deficiency.
The simple virilizing form of classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (classical 21 OHD CAH; see this term) is characterized by genital ambiguity and virilization of the external genitalia in females, hypocortisolism and precocious pseudopuberty without salt-wasting.
, that usually begins with gastrointestinal symptoms (e.g. abdominal pain, nausea, vomiting, and diarrhea, that cause severe dehydration) and an initial leukocytosis leading to marrow failure (24 hours after ingestion), followed by potentially fatal multi-organ failure with mental status change, oliguric renal failure, disseminated intravascular coagulation, electrolyte imbalance, acid-base disturbance, cardiac failure/arrest and shock within 1-3 days.
Methanol poisoning is a rare poisoning resulting in elevated anion gap metabolic acidosis, due to the alcohol dehydrogenase (ADH)-mediated production of formic acid (which is poisonous to the central nervous system), and characterized by dizziness, nausea, vomiting, confusion, metabolic acidosis, visual disturbances (which if left untreated can lead to blindness), coma, and death (due to respiratory failure).
Digitalis (digoxin) poisoning is a potentially life-threatening poisoning that provokes conduction disturbances, characterized by increased automaticity and decreased conduction. Acute poisoning presents with the common initial manifestations of nausea and vomiting, cardiovascular manifestations (bradycardia, heart block and a variety of dysrhythmias), central nervous system manifestations (lethargy, confusion and weakness) and hyperkalemia. Chronic poisoning is more insidious, manifesting with gastrointestinal symptoms, altered mental status, and visual disturbances.
Chondroectodermal dysplasia with night blindness is a rare genetic bone development disorder characterized by proportionate short stature, nail dysplasia (enlarged, convex, hypertrophic nails), hypodontia and night blindness. Osteopenia, a tendency to present fractures, talipes varus with abnormal gait, ear infections, and watering eyes due to narrow tear ducts are frequently associated. Radiologically patients present delayed bone age on wrist X-rays, platyspondyly, and broad metaphyses of humeri with dense and thickened growth plates.
Lujo hemorrhagic fever, caused by the Lujo virus (a newly discovered Old World arenavirus) is a zoonotic disease from Zambia, Africa, whose reservoir is unknown and is characterized by fever and hemorrhagic manifestations with an extremely high fatality rate of 80% (in the 5 reported cases to date) and a moderate to high level of nosocomial transmission.
Chapare hemorrhagic fever, caused by the Chapare virus (a new arenavirus), discovered from a small outbreak in Cochabamba, Bolivia between 2003 and 2004, is an acute viral hemorrhagic fever characterized by fever, myalgia, arthralgia, and multiple hemorrhagic signs. About a third of untreated cases go on to develop more severe symptoms with delirium, coma and convulsions and death (in one case). No other cases have been reported since.
Renal medullary carcinoma is a rare, aggressive subtype of renal cell carcinoma characterized by a large, white or tan, firm, infiltrative tumor with microabscess-like foci centered in the renal medulla, typically presenting with hematuria, abdominal/flank pain, weight loss and fever. It is associated with sickle cell trait and disease and metastasis to the bones and lungs is common at time of diagnosis.
Tubulocystic renal cell carcinoma is an extremely rare subtype of renal cell carcinoma most frequently characterized by a small, solitary, well-circumscribed, unencapsulated renal tumor composed of multiple small to medium-sized cysts with a white or gray, spongy (""bubble wrap-like"") cut surface. Patients are usually asymptomatic or could manifest with abdominal pain, abdominal distension and/or hematuria. Progression, recurrence and metastasis rarely occur although lymph node, bone, pleura and liver mestatsis have been reported.
Autosomal recessive (AR) mendelian susceptibility to mycobacterial diseases (MSMD) due to a complete deficiency describes a group of genetic variants of MSMD (see this term) comprised of MSMD due to complete interferon gamma receptor 1 (IFN-gammaR1) deficiency, complete IFN-gammaR2 deficiency, complete interleukin-12 subunit beta (IL12B) deficiency, complete interleukin-12 receptor subunit beta-1 (IL-12RB1) deficiency and complete ISG15 deficiency (see these terms).
genes which lead to a residual response of IFN-gamma.
Autosomal dominant (AD) mendelian susceptibility to mycobacterial diseases (MSMD) due to a partial deficiency describes a group of variants of MSMD (see this term) due to dominantly inherited partial deficiencies in interferon gamma receptor 1 (IFN-gammaR1), IFN-gammaR2, signal transducer and activator of transcription 1 (STAT1) or interferon regulator factor 8 (IRF8) (see these terms).
Mendelian susceptibily to mycobacterial diseases (MSMD) due to complete interferon gamma receptor 2 (IFN-gammaR2) deficiency is a genetic variant of MSMD (see this term) characterized by a complete deficiency in IFN-gammaR2, leading to an undetectable response to IFN-gamma, and consequently, to severe and often fatal infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
Autosomal recessive (AR) mendelian susceptibility to mycobacterial diseases (MSMD) due to partial IFN-gammaR1 deficiency is a genetic variant of MSMD (see this term) characterized by a partial deficiency in IFN-gammaR1, leading to a residual response to IFN-gamma and, consequently, to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
Autosomal recessive mendelian susceptibility to mycobacterial diseases (MSMD) due to partial IFNgammaR2 deficiency is a genetic variant of MSMD (see this term) characterized by a partial deficiency in IFN-gammaR2, leading to a residual response to IFN-gamma and consequently to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
Autosomal dominant (AD) mendelian susceptibility to mycobacterial diseases (MSMD) due to partial interferon gamma receptor 2 (IFN-gammaR2) deficiency is a genetic variant of MSMD (see this term) characterized by a partial deficiency in IFN-gammaR2, leading to impaired response to IFN-gamma and, consequently, to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
) genes. They are characterized by mycobacterial infections, occuring in males.
Apparent mineralocorticoid excess (AME) is a rare form of pseudohyperaldosteronism characterized by very early-onset and severe hypertension, associated with low renin levels and hypoaldosteronism.
Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial capillary malformations and/or cerebral and ocular ipsilateral vascular malformations that result in variable degrees of ocular and neurological anomalies.
Multiple osteochondromas (MO) is characterised by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones.
Multiple synostoses syndrome (MSS) is a rare developmental bone disorder characterized by proximal symphalangism of the fingers and/or toes often associated with fusion of carpal and tarsal, humeroradial, and cervical spine joints.
Hyperinsulinism due to HNF1A deficiency is a form of diazoxide-sensitive diffuse hyperinsulinism (DHI), characterized by transient or persistent hyperinsulinemic hypoglycemia (HH) in infancy that is responsive to diazoxide, evolving in to maturity-onset diabetes of the young subtype 1 (MODY-1; see this term) later in life.
Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Piedmont type is a form of HCHWA (see this term) characterized by an age of onset between 50-70 years of age, recurrent lobar intracerebral hemorrhages and cognitive decline.
Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Iowa type is a form of HCHWA (see this term) characterized by age of onset between 50-66 years of age, memory impairment, myoclonic jerks, expressive dysphagia, short-stepped gait, personality changes and lobar intracerebral hemorrhages.
Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Italian type is a form of HCHWA (see this term) characterized by an age of onset of 50 years of age, dementia and lobar intracerebral hemorrhage.
Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Flemish type is a form of HCHWA (see this term) characterized by an age of onset of 45 years of age, progressive Alzheimer's disease-like dementia and lobar intracerebral hemorrhage in some patients.
Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Arctic type is a form of HCHWA (see this term) characterized by an age of onset of 54-61 years and progressive Alzheimer's disease-like dementia, without intracerebral hemorrhages.
SRD5A3-CDG is a rare, non X-linked congenital disorder of gyclosylation due to steroid 5 alpha reductase type 3 deficiency characterized by a highly variable phenotype typically presenting with severe visual impairment, variable ocular anomalies (such as optic nerve hypoplasia/atrophy, iris and optic nerve coloboma, congenital cataract, glaucoma), intellectual disability, cerebellar abnormalities, nystagmus, hypotonia, ataxia, and/or ichthyosiform skin lesions. Other reported manifestations include retinitis pigmentosa, kyphosis, congenital heart defects, hypertrichosis and abnormal coagulation.
Joint contractures, muscle atrophy, microcytic anemia and panniculitis-induced lipodystrophy (JMP) syndrome is a rare autoinflammatory disorder belonging to the proteasome disability syndrome (see this term) group and characterized by sclerodermic skin with the presence of erythematous lesions, joint contractures, generalized or partial lipodystrophy, muscle atrophy and short stature.
Telecanthus-hypertelorism-strabismus-pes cavus syndrome is characterized by telecanthus, hypertelorism, strabismus, pes cavus and other variable anomalies. It has been described in a father and his son. The son also had hypospadias, bilateral inguinal hernia, clinodactyly and camptodactyly of the fingers, and radiographic findings including flared metaphyses of the long bones and osteopenia.
Spastic paraplegia-Paget disease of bone syndrome is an extremely rare, complex form of hereditary spastic paraplegia characterized by a slowly progressive spastic paraplegia (with increased muscle tone, decreased strength in the anterior tibial muscles and hyperreflexia in the lower extremities with Babinski sign) presenting in adulthood, associated with Paget disease of the bone. Cognitive decline, dementia and myopathic changes at muscle biopsy have not been reported.
Transient neonatal multiple acyl-CoA dehydrogenase deficiency describes a very rare condition where a maternal riboflavin deficiency causes an infant to present with manifestations similar to those seen in multiple acyl-CoA dehydrogenase (MAD) deficiency (see this term) such as poor suck, metabolic acidosis and hypoglycemia, but that resolves completely with oral riboflavin. In the one patient described haploinsufficiency of the human riboflavin transporter (hRFT1) was described in the mother.
Classic endocrine tumor of the appendix is a type of endocrine tumor of the appendix (see this term), seen twice as frequently in females than in males, and usually presenting before the fifth decade of life. Classic endocrine tumor of the appendix is usually asymptomatic when located in the tip of the appendix (without obstruction), but acute appendicitis is often associated.
Granulomatous slack skin (GSS) is a variant of mycosis fungoides (MF; see this term), a form of cutaneous T-cell lymphoma, and is characterized by the presence of circumscribed areas of pendulous lax skin.
Congenital intrinsic factor deficiency (IFD) is a rare disorder of vitamin B12 (cobalamin) absorption that is characterized by megaloblastic anemia and neurological abnormalities.
Hypoplastic tibia-polydactyly syndrome is a very rare congenital malformation syndrome characterized by bilateral hypoplasia of the tibia with polydactyly of the feet and hands.
Pediatric hepatocellular carcinoma (pediatric HCC) is a rare, aggressive, malignant hepatic tumor that develops mainly in children over 10 years of age.
Tracheobronchopathia osteochondroplastica (TO) is an idiopathic and benign disease of the large airways characterized by submucosal osteocartilaginous nodules presenting in the trachea with or without the involvement of the major bronchi.
Congenital deficiencies of fibrinogen are coagulation disorders characterized by bleeding symptoms ranging from mild to severe resulting from reduced quantity and/or quality of circulating fibrinogen. Afibrinogenemia (complete absence of fibrinogen) and hypofibrinogenemia (reduced plasma fibrinogen concentration) (see these terms) correspond to quantitative anomalies of fibrinogen while dysfibrinogenemia (see this term) corresponds to a functional anomaly of fibrinogen. Hypo- and dysfibrinogenemia may be frequently combined (hypodysfibrinogenemia).
Trigonocephaly-broad thumbs syndrome is characterized by neonatal trigonocephaly and multiple anomalies including craniosynostosis, shallow orbits, unusual nose, deviation of the terminal phalanges of fingers 1, 2, and 5, and broad toes with duplication of the terminal phalanx. It has been described in a mother and her son. It is transmitted as an autosomal dominant trait.
Trisomy 13 is a chromosomal anomaly caused by the presence of an extra chromosome 13 and is characterized by brain malformations (holoprosencephaly), facial dysmorphism, ocular anomalies, postaxial polydactyly, visceral malformations (cardiopathy) and severe psychomotor retardation.
Familial multiple fibrofolliculoma is a genodermatosis characterised by the presence of multiple hamartomas of the hair follicle. It has been described in one family so far.
Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne potentially severe hemorrhagic disease caused by Old World Hantaviruses characterized by high fever, malaise, headache, myalgia, arthralgia, backache, abdominal pain, oliguria/renal failure and systemic hemorrhagic manifestations.
Transient tyrosinemia of the newborn is a benign disorder of tyrosine metabolism detected upon newborn screening and often observed in premature infants. It shows no clinical symptoms. It is characterized by tyrosinemia, moderate hyperphenylalaninemia, and tyrosiluria that usually resolve after 2 months of age.
Ulerythema ophryogenesis is characterised by inflammatory keratotic papules occurring on the face, which may be followed by scars, atrophy and alopecia. Prevalence is unknown but the disease, affecting mainly children and young adults, is rare. Erythema with mild hyperkeratosis of the hair follicles resulting in rough papules is observed on the cheeks and lateral aspects of the eyebrows. The disorder occasionally extends to the adjacent scalp, ears and forehead and rarely to the extensor surfaces of the limbs. Symptoms regress with age, although loss of the lateral aspects of the eyebrows can occur. Many cases occur sporadically; autosomal dominant inheritance has also been reported. There is no particular treatment, but patients should avoid sun exposure without UV protection.
Viral hemorrhagic fever is a group of recently discovered contagious viral infections characterized by severe, multiple, and often fatal hemorrhages. African fevers include Lassa fever discovered in 1969, Marburg's disease that first occurred in 1967, and Ebola fever that appeared in 1976. Other viruses may also cause hemorrhagic fevers (for example, arbovirus fever).
Weaver-Williams syndrome is a multiple congenital anomalies syndrome characterized by moderate-to-severe intellectual disability, decreased muscle mass, microcephaly, facial dysmorphism (prominent ears, midfacial hypoplasia, small mouth and cleft palate), clinodactyly of the fingers, delayed osseous maturation and generalized bone hypoplasia. The syndrome has been described in a brother and sister and an autosomal recessive mode of inheritance has been suggested. There have been no further descriptions in the literature since 1977.
Familial primary hypomagnesemia with normocalciuria and normocalcemia (FPHNN) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by low serum magnesium (Mg) values but inappropriate normal urinary Mg values (i.e. renal hypomagnesemia). The typical symptoms are weakness of the limbs, vertigo, headaches, seizures, brisk tendon reflexes and mild to moderate psychomotor delay.
Fulminant viral hepatitis is a rapid and severe impairment of liver functions (acute liver failure) with hepatic encephalopathy developing less than 8 weeks after the onset of jaundice, secondary to viral hepatitis mainly due to HBV, but also to HAV.
Infantile neuroaxonal dystrophy/atypical neuroaxonal dystrophy (INAD/atypical NAD) is a type of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by psychomotor delay and regression, increasing neurological involvement with symmetrical pyramidal tract signs and spastic tetraplegia. INAD may be classic or atypical and patients present with symptoms anywhere along a continuum between the two.
Isolated synostotic plagiocephaly (SP) is a form of nonsyndromic craniosynostosis characterized by premature fusion of one coronal suture leading to skull deformity and facial asymmetry.
Brain dopamine-serotonin vesicular transport disease is a newly discovered infantile-onset neurometabolic disease characterized by dystonia, parkinsonism, nonambulation, autonomic dysfunction, developmental delay and mood disturbances.
Attenuated Chédiak-Higashi syndrome (CHS) is a very rare and atypical form of CHS (see this term), a genetic disorder characterized by partial oculocutaneous albinism (OCA, see this term), severe immunodeficiency, mild bleeding, neurological dysfunction and lymphoproliferative disorder.
Type 1 minimal pigment oculocutaneous albinism (OCA1-MP) is an extremely rare form of OCA1 (see this term) with minimal pigment present, characterized by blond hair, variable iris transillumination, visual acuity ranging from 20/80-20/200 and white skin, with or without skin nevi.
Oculocutaneous albinism type 7 (OCA7), formerly called OCA5, is a form of oculocutaneous albinism (OCA; see this term) characterized by skin and hair hypopigmentation, nystagmus and iris transillumination.
Infantile pyruvate carboxylase (PC) deficiency (Type A) is a rare, severe form of PC deficiency (see this term) characterized by infantile-onset, mild to moderate lactic acidemia, and a generally severe course.
Severe neonatal pyruvate carboxylase (PC) deficiency (Type B) is a rare, extremely severe form of PC deficiency (see this term) characterized by severe, early-onset metabolic acidosis, and a generally fatal outcome in early infancy.
Benign pyruvate carboxylase (PC) deficiency (Type C) is a rare, very mild form of PC deficiency (see this term) characterized by episodic metabolic acidosis and normal or mildly delayed neurological development.
ALDH18A1-related De Barsy syndrome combines intellectual deficit, bilateral cataracts, and skin and joint hyperlaxity.
Malignant sex cord stromal tumor (SCST) of ovary is a rare ovarian cancer (see this term) arising from granulosa, theca, sertoli and leydig cells or stromal fibroblasts, occurring at any age and presenting with abdominal or pelvic mass, and characterized (with the exception of fibroma) by the production of sex steroids resulting in manifestations of hormone excess, with a relatively favorable prognosis.
Familial glucocorticoid deficiency (FGD) is a group of primary adrenal insufficiencies characterized clinically by neonatal hyperpigmentation, hypoglycemia, failure to thrive, and recurrent infections, and biochemically by glucocorticoid deficiency without mineralocorticoid deficiency.
Staphylococcal necrotizing pneumonia is a rare, bacterial, pulmonary infectious disease, caused by a Panton-Valentine leukocidin-producing Staphylococcus aureus strain, characterized by severe respiratory failure, extensive, rapidly progressing pneumonia and hemorrhagic lung necrosis. Patients typically present with influenza-like symptoms, such as fever, cough, and chest pain, as well as hemoptysis, hypotension, leukopenia, and severe respiratory symptoms that rapidly evolve to acute respiratory distress syndrome and septic shock. High mortality is associated.
Gastric linitis plastica (gastric LP) is a malignant, diffuse, infiltrative gastric adenocarcinoma.
Testicular non seminomatous germ cell tumor describes a group of testicular germ cell tumors (see this term) occurring in the third decade of life (mean age: 25 years) with a usually painless unilateral mass in the scrotum or in some cases with gynaecomastia and/or back and flack pain and characterized by a more aggressive clinical course than testicular seminomatous germ cell tumors (see this term) with rapid involvement of blood vessels and a poorer prognosis. Histologically, they can be either undifferentiated (embryonal carcinoma), differentiated (teratoma, yolk sac tumor, choriocarcinoma), or can consist of a mixture of seminomatous and nonseminomatous components.
1qter deletion syndrome is a chromosomal anomaly characterized by an intellectual deficiency, progressive microcephaly, seizures, growth delay, distinct facial dysmorphic features and various midline defects including cardiac, corpus callosum, gastro-oesophalgeal and urogenital anomalies.
Alexander disease type I (AxD type I) is an astrogliopathy and the most severe and common form of Alexander disease (AxD; see this term), presenting before the age of 4 and characterized by seizures, megalencephaly and developmental delay with progressive deterioration.
Alexander disease type II (AxD type II) is an astrogliopathy and a form of Alexander disease (AxD; see this term) characterized by ataxia, bulbar symptoms, spastic paraparesis, palatal myoclonus, and autonomic symptoms.
Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood is a rare and very aggressive neoplastic disease emerging after a primary acute or chronic active EBV infection. It presents with persisting fever and malaise, hepatosplenomegaly with or without lymphadenopathy, liver failure, severe pancytopenia and a rapid progression towards multi-organ failure and hemophagocytic syndrome with a fatal issue. It is characterized by clonal proliferation of EBV-infected T cells with an activated cytotoxic phenotype.
Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma is a very rare variant of diffuse large B-cell lymphoma (DLBCL; see this term) mainly affecting middle-aged immunocompetent men and characterized by a consistent primary involvement of lymph nodes (mainly in the cervical and mediastinum lymph nodes) and with infrequent extra nodal involvement of the bone marrow and other extra-nodal sites (head and neck region, liver, spleen, and gastrointestinal tract). It has an aggressive disease course, and is associated with a poor prognosis.
Hypocomplementemic urticarial vasculitis (HUV) is an immune complex-mediated small vessel vasculitis characterized by urticaria and hypocomplementemia (low C1q with or without low C3 and C4), and usually associated with circulating anti-C1q autoantibodies. Arthritis, pulmonary disease, ocular inflammation, and glomerulonephritis are common systemic manifestations.
Glycogen debranching enzyme (GDE) deficiency, or glycogen storage disease type 3 (GSD 3), is a form of glycogen storage disease characterized by severe muscle weakness and hepatopathy.
Glycogen branching enzyme (GBE) deficiency (Andersen's disease or amylopectinosis), or glycogen storage disease type 4 (GSD4), is a rare and severe form of glycogen storage disease which accounts for approximately 3% of all the glycogen storage diseases (see these terms).
or in therapy-related AML cases, and is characterized by frequent extramedullary involvement (mainly hepatomegaly, splenomegaly, lymphadenopathies, cutaneous infiltration, but also gum, bone, central nervous system, testicles involvement), severe coagulation disorder (disseminated intravascular coagulopathy or primary fibrinolysis) and poor prognosis. Morphologically, a blast population with a myelomonocytic stage of differentiation is observed.
exposure to carbamazepine, in combination with valproate, has been associated with significant developmental delay (particularly affecting verbal intelligence) and a high rate of congenital anomalies.
Oculocutaneous albinism type 5 (OCA5) is a type of oculocutaneous albinism (see this term) found in one Pakistani family to date, characterized by white skin, golden hair, photophobia, nystagmus, foveal hypoplasia and impaired visual acuity, that affects males and females equally, and that has been mapped to a locus on chromosome 4q24 but whose gene has not yet been discovered.
Medich giant platelet syndrome (MGPS) is a platelet granule disorder characterized by thrombocytopenia with giant platelets resulting in easy bleeding.
Interstitial cystitis, also known as bladder pain syndrome (IC/BPS), is a rare chronic debilitating urogenital disease characterized by urinary frequency, urgency, and pelvic pain.
Acquired progressive kinking of the hair (APKH) is a rare hair disorder characterized by the appearance of lustreless, curly, frizzy, and coarse hair generally during adolescence predominantly in the frontal, temporal, and vertex regions of the scalp. Eyelashes, as well as growth and pigmentation of the hair, may also be affected.
Dihydropyrimidinase (DPD) deficiency is a very rare pyrimidine metabolism disorder with a variable clinical presentation including gastrointestinal manifestations (feeding problems, cyclic vomiting, gastroesophageal reflux, malabsorption with villous atrophy), hypotonia, intellectual deficit, seizures, and less frequently growth retardation, failure to thrive, microcephaly and autism. Asymptomatic cases are also reported. DPD deficiency increases the risk of 5-FU toxicity.
Uveal melanoma is a rare tumor of the eye, arising from the choroid in 90% of cases and from the iris and ciliary body in the other 10% of cases, which clinically presents with visual symptoms (including blurred vision, photopsia, floaters, and visual field reduction), a visible mass and pain. Fatal metastatic disease is seen in about half of all patients, with the liver being the most frequent site of metastasis.
Classical Hodgkin lymphoma (CHL) is a B-cell lymphoma characterized histologically by the presence of large mononuclear Hodgkin cells and multinucleated Reed-Sternberg (HRS) cells.
Atypical juvenile parkinsonism (AJP) is a complex form of young-onset Parkinson disease (YOPD; see this term) that manifests with pyramidal signs, eye movement abnormalities, psychiatric manifestations (depression, anxiety, drug-induced psychosis, and impulse control disorders), intellectual disability, and other neurological symptoms (such as ataxia and epilepsy) along with classical parkinsonian symptoms.
HSD10 disease is a rare, life-threatening neurometabolic disease characterized by a progressive neurodegenerative course, epilepsy, retinopathy and progressive cardiomyopathy.
HSD10 disease, infantile type is a clinical subtype of HSD10 disease, a rare neurometabolic disorder. It is characterized by normal early development until 6-18 months of life, followed by progressive neurodegeneration manifesting with developmental regression, progressive visual and hearing troubles, seizures, epilepsy, severe cardiomyopathy, lethargy, hypotonia, poor feeding, choreoathetosis, and movement disorders. Elevated blood levels of isoleucine metabolites and their excretion in urine are reported. The disease is usually fatal around 2-4 years of age.
HSD10 disease, neonatal type is the most severe form of HSD10 disease, a rare neurometabolic disorder. It is characterized by onset of severe metabolic/lactic acidosis, neurological and psychomotor delay, seizures and severe progressive hypertrophic cardiomyopathy in the neonatal period. Hepatic involvement and coagulopathy are rare. The disease is fatal within the first months of life.
Acquired myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction characterized by fatigable muscle weakness with frequent ocular signs and/or generalized muscle weakness, and occasionally associated with thymoma (see this term).
Juvenile myasthenia gravis (MG; see this term) is a rare form of MG, an autoimmune disorder of the neuromuscular junction resulting in ocular manifestations or generalized weakness, with onset before 18 years of age.
Transient neonatal myasthenia gravis (MG) is a rare form of MG (see this term) occurring in neonates born to mothers who have the disorder or specific circulating autoantibodies.
Feingold syndrome type 1 (FS1) is a rare inherited malformation syndrome characterized by microcephaly, short stature and numerous digital anomalies.
46,XX testicular disorder of sex development (46,XX testicular DSD) is characterized by male external genitalia, ranging from normal to ambiguous with associated testosterone deficiency.
Chronic hiccup is a rare movement disorder characterized by involuntary spasmodic contractions of the inspiratory muscles synchronized with larynx closure lasting for more than 48 hours.
Acitretin/Etretinate embryopathy is a teratogenic disorder due to acitretin or etretinate exposure during the first trimester of pregnancy, carrying a risk of fetal malformations of approximately 20%, including central nervous system, craniofacial, ear, thymic, cardiac and limb anomalies.
Isolated glycerol kinase deficiency (GKD) is a very rare X-linked disorder of glycerol metabolism characterized biochemically by elevated plasma and urine glycerol levels, and clinically by variable neurometabolic manifestations, depending on the age of onset, and varying from a life-threatening childhood metabolic crisis to an asymptomatic adult form (infantile GKD, juvenile GKD, and adult GKD (see these terms)).
Gyrate atrophy of the choroid and retina (GACR) is a very rare, inherited retinal dystrophy, characterized by progressive chorioretinal atrophy, myopia and early cataract.
. (However, the majority of patients carrying an HPAH mutation do not develop PAH). Idiopathic pulmonary arterial hypertension (IFPAH; see this term) refers to those cases of pulmonary arterial hypertension in which etiology remains unknown .
PFAPA (Periodic fever - aphthous stomatitis- pharyngitis - adenopathy) syndrome is an auto inflammatory syndrome characterized by recurrent febrile episodes associated with aphthous stomatitis, pharyngitis and cervical adenitis.
Aldosterone synthase deficiency is a rare inherited defect of the final step of aldosterone biosynthesis (conversion of deoxycorticosterone to aldosterone).
Autosomal dominant hypocalcemia (AD hypocalcemia) is a disorder of calcium homeostasis characterized by variable degrees of hypocalcemia with abnormally low levels of parathyroid hormone (PTH) and persistant normal or elevated calciuria.
Hypospadias is the displacement of the urethral meatus on the ventrum of the penis. This abnormality is associated with a varyingly bent, twisted penis and opened dorsal prepuce.
Pure autonomic failure (PAF) is a neurodegenerative disease that affects the sympathetic branch of the autonomous nervous system and that manifests with orthostatic hypotension.
Idiopathic neonatal atrial flutter (AFL) is a rare rhythm disorder, characterized by sustained tachycardia in newborns and infants with an atrial rate often at around 440 beats/minute (range 340-580). AFL may manifest as asymptomatic tachycardia, congestive heart failure or hydrops.
Recessive X-linked ichthyosis (RXLI) is a genodermatosis belonging to the Mendelian Disorders of Cornification (MeDOC) and characterized by generalized hyperkeratosis and scaling of the skin.
Oligodendrogliomas are cerebral tumors that are differentiated from other gliomas on the basis of their unique genetic characteristics and better response to chemotherapy. These tumors are classified according to their grade (low grade oligodendrogliomas: grade II of the WHO classification and anaplastic oligodendrogliomas: grade III of the WHO classification) and according to their pure or mixed histology (oligoastrocytomas).
Hereditary persistence of fetal hemoglobin (HPFH) associated with beta-thalassemia (see this term) is characterized by high hemoglobin (Hb) F levels and an increased number of fetal-Hb-containing-cells.
Hereditary papillary renal cell carcinoma (HPRCC) is a familial renal cancer syndrome characterised by a predisposition for developing bilateral and multifocal type 1 papillary renal carcinomas.
Keratitis (and hystrix-like) ichthyosis deafness (KID/HID) syndrome is a rare congenital ectodermal disorder characterized by vascularizing keratitis, hyperkeratotic skin lesions and hearing loss.
Nodular regenerative hyperplasia of the liver is a rare parenchymatous liver disease characterized by diffuse benign transformation of the hepatic parenchyma into multiple small nodules (composed of regenerating hepatocytes) and that is usually asymptomatic but can lead to the development of non-cirrhotic portal hypertension and its complications, including esophageal variceal bleeding, hypersplenism and ascites. It is often associated with rheumatologic, autoimmune, hematologic, and myeloproliferative disorders as well as various immune deficiency states and exposure certain drugs and toxins.
Proliferating trichilemmal tumor is a rare large, multinodular, usually benign, tumor that is generally located in the posterior part of the scalp in aged women (over 50 years). It first appears as a painless nodule that later grows into a solid or partially cystic tumor that is mobile over the underlying subcutaneous tissues. It can present ulceration, inflammation or even bleeding and can cause necrosis of the adjacent tissues.
Purpura fulminans (PF) is a life-threatening, rapidly progressive thrombotic disorder affecting mainly neonates and children that is characterized by purpuric skin lesions and disseminated intravascular coagulation. PF may progress rapidly to multi-organ failure caused by thrombotic occlusion of small and medium-sized blood vessels. There are two forms of PF that are classified according to triggering mechanisms: acute infectious (the most common form), and idiopathic PF.
Lichen amyloidosis is a rare chronic form of cutaneous amyloidosis (see this term), a skin disease characterized by the accumulation of amyloid deposits in the dermis, clinically characterized by the development of pruritic, often pigmented, hyperkeratotic papules on trunk and extremities, especially on the shins, and histologically by the deposition of amyloid or amyloid-like proteins in the papillary dermis.
Graham Little-Piccardi-Lassueur syndrome is a variant of lichen planopilaris (see this term) characterized by the clinical triad of progressive cicatricial (scarring) alopecia of the scalp, follicular keratotic papules on glabrous skin, and variable alopecia of the axillae and groin.
Microlissencephaly-micromelia syndrome is a syndrome of abnormal cortical development, characterized by severe prenatal polyhydramnios, postnatal microcephaly, lissencephaly, upper limb micromelia, dysmorphic facies (coarse face, hypertrichosis, and short nose with long philtrum), intractable seizures, and early death. Hypoparathyroidism was noted in one case.
Zellweger-like syndrome without peroxisomal anomalies is an extremely rare mitochondrial disorder characterized by facial dysmorphism similar to that seen in Zellweger syndrome (see this term), such as frontal bossing, high forehead, upslanting palpebral fissures, hypoplastic supraorbital ridges, and epicanthal folds, and in addition, pale skin, profound hypotonia, developmental delay, and minor metabolic anomalies. No peroxysomal defects, however, have been reported. Transmission is thought to be autosomal recessive.
, that is transmitted to humans via a scratch or bite of an infected cat and that has a variable clinical presentation but that usually manifests with an erythematous papule at the site of inoculation followed by chronic regional lymphadenopathy. Clinical course is usually self-limiting but disseminated illness with high fever, hepatosplenomegaly, granulomatous osteolytic lesions, encephalitis, retinitis, and atypical pneumonia can also occur. Cat-scratch disease can atypically present as parinaud oculoglandular syndrome (unilateral conjunctivitis and preauricular lymphadenopathy).
Acute monoblastic leukemia (AML-M5), is one of the most common subtypes of acute myeloid leukemia (AML; see this term) that is either comprised of more than 80% of monoblasts (AML-M5a) or 30-80% monoblasts with (pro)monocytic differentiation (AML-M5b). AML-M5 presents with asthenia, pallor, fever, and dizziness. Specific features of AML-M5 include hyperleukocytosis, propensity for extramedullary infiltrates, coagulation abnormalities including disseminated intravascular coagulation and neurological disorders. Leukemia cutis and gingival infiltration can also be seen. A characteristic translocation observed in AML-M5 is t(9;11).
Idiopathic arterial calcification of infancy is a rare condition characterized by extensive calcification and stenosis of the large and medium sized arteries.
Berardinelli-Seip congenital lipodystrophy (BSCL) is characterized by the association of lipoatrophy, hypertriglyceridemia, hepatomegaly and acromegaloid features. BSCL belongs to the group of extreme insulin resistance syndromes, which also includes leprechaunism, Rabson-Mendenhall syndrome, acquired generalized lipodystrophy, and types A and B insulin resistance (see these terms).
Roch-Leri mesosomatous lipomatosis is a rare benign autosomal dominant disorder of fat tissue proliferation characterized by the presence of multiple small lipomas of 2 to 5 cm in diameter in the middle third of the body (i.e. the forearms, trunk, and upper thighs), and which are generally painless and can be easily removed by local anesthesia, provided that they are not too numerous or confluent. There have been no further descriptions in the literature since 1984.
Orbital leiomyoma is a rare benign smooth muscle tumor arising from the walls of orbital vessels characterized by its slow growth and well encapsulated nature. It is usually located in an extraconal position, commonly manifesting with painless proptosis. The tumor is composed of spindle cells arranged in a fibrous stroma rich in dilated sinusoidal capillaries. The nuclei of tumor cells are oval with blunted ends and there are no mitotic figures. Orbital leiomyoma when excised has excellent prognosis for vision and life. One case of orbital leiomyosarcoma that possibly represents sarcomatous change in an orbital leiomyoma following radiation treatment has been reported.
Lyell syndrome is an extended form of toxic epidermal necrolysis (see this term) characterized by destruction and detachment of the skin epithelium and mucous membranes involving more than 30% of the body surface area.
Familial Hemophagocytic lymphohistiocytosis (FHL) is a rare primary immunodeficiency characterized by a macrophage activation syndrome (see this term) with an onset usually occurring within a few months or less common several years after birth.
Cutaneous lymphoma is a heterogeneous entity with respect to its clinical and pathological features, evolutive profile, prognosis, molecular aetiology and response to therapy. These specifications have been taken into account in recent classifications, which have placed particular importance on the prognostic implications of these different entities.
Posterior Cortical Atrophy (PCA) is a rare progressive neurodegenerative disorder with a typical onset between 50-65 years of age characterized by progressive impairment of higher visual processing skills and other posterior cortical functions without any evidence of ocular abnormalities.
Corticosteroid-sensitive aseptic abscesses syndrome is a well-defined entity within the group of autoinflammatory disorders.
Legionellosis or Legionnaires' disease (LD) is a bacterial lung infection characterized by a potentially fatal pneumonia.
Cushing's syndrome (CS) encompasses a group of hormonal disorders caused by prolonged and high exposure levels to glucocorticoids that can be of either endogenous (adrenal cortex production) or exogenous (iatrogenic) origin.
Malakoplakia is a chronic multisystem granulomatous inflammatory disease characterized by the presence of single or multiple soft plaques on various organs of the body.
Carcinoma of the gallbladder (GBC) is the most common and aggressive form of biliary tract cancer (BTC; see this term) usually arising in the fundus of the gallbladder, rapidly metastasizing to lymph nodes and distant sites.
Cold agglutinin disease is a type of autoimmune hemolytic anemia (see this term) defined by the presence of cold autoantibodies (autoantibodies which are active at temperatures below 30°C).
22q11.2 deletion syndrome (DS) is a chromosomal anomaly which causes a congenital malformation disorder whose common features include cardiac defects, palatal anomalies, facial dysmorphism, developmental delay and immune deficiency.
Cirrhotic cardiomyopathy is the term used to describe a constellation of features indicative of abnormal heart structure and function in patients with cirrhosis. These include systolic and diastolic dysfunction, electrophysiological changes, and macroscopic and microscopic structural changes.
Mazabraud syndrome is a rare primary bone dysplasia (see this term) characterized by the association of fibrous dysplasia with intramuscular myxomas. Fibrous dysplasia (usually polyostotic, sometimes monostotic) occurs during the growth period and can be asymptomatic or can present with pain, skeletal deformities or fractures while intramuscular myxoma, associated with polyostotic fibrous dysplasia (see this term) is usually multifocal, typically occuring in the vicinity of skeletal lesions, and presents in adulthood as a painless soft-tissue mass (most commonly in the thigh). Although it is a benign condition, local recurrences of myxomas after incomplete excision and malignant transformation of a fibrous dysplastic lesion into osteogenic sarcoma have been reported.
Mucopolysaccharidosis type 2 (MPS2) is a lysosomal storage disease leading to a massive accumulation of glycosaminoglycans and a wide variety of symptoms including distinctive coarse facial features, short stature, cardio-respiratory involvement and skeletal abnormalities. It manifests as a continuum varying from a severe to an attenuated form without neuronal involvement.
Mucopolysaccharidosis type III (MPS III) is a lysosomal storage disease belonging to the group of mucopolysaccharidoses and characterised by severe and rapid intellectual deterioration.
Distal myopathy with vocal cord and pharyngeal weakness is an adult-onset, autosomal dominant muscular disease which is characterized by muscle weakness in the feet and hands, combined with vocal or swallowing dysfunction.
Nonaka distal myopathy (described in Japan) and the quadriceps-sparing autosomal recessive inclusion body myopathy type 2 (IBM2; independently described in Iranian Jews and later in other Jewish and non-Jewish populations) constitute the same pathological entity, distinguished by the sparing of quadriceps.
Welander distal myopathy (WDM) is a distal myopathy (see this term), characterized by weakness in the distal upper extremities, usually finger and wrist extensors which later progresses to all hand muscles and distal lower extremity, primarily in toe and ankle extensors.
Potassium-aggravated myotonia (PAM) is a muscular channelopathy presenting with a pure myotonia dramatically aggravated by potassium ingestion, with variable cold sensitivity and no episodic weakness. This group includes three forms: myotonia fluctuans, myotonia permanens, and acetazolamide-responsive myotonia (see these terms).
Myotonia congenita is characterised by slow muscle relaxation associated with hyperexcitation of the muscle fibres.
Congenital primary megaureter (PM) is an idiopathic condition in which the bladder and bladder outlet are normal but the ureter is dilated to some extent. It may be obstructed, refluxing or unobstructed and not refluxing.
Acrofacial dysostosis, Kennedy-Teebi type was reported as a new type of acrofacial dysostosis (see this term) due to the presence of manifestations not usually seen in Nager syndrome (NS; see this term) such as microcephaly, blepharophimosis, microtia, a peculiar beakednose, cleft lip and palate, symmetrical involvement of the thumbs and great toes and developmental delay. It has since been suggested that these features can also be a part of the NS phenotype.
Tolosa-Hunt syndrome is an ophthalmoplegic syndrome, affecting all age groups, characterized by acute attacks (lasting a few days to a few weeks) of periorbital pain, ipsilateral ocular motor nerve palsies, ptosis, disordered eye movements and blurred vision usually caused by a non-specific inflammatory process in the cavernous sinus and superior orbital fissure. It has an unpredicatable course with spontaneous remission occurring in some and recurrence of attacks in others.
Iridocorneal endothelial (ICE) syndrome describes a group of progressive corneal proliferative endotheliopathies comprised of Chandler?s syndrome, Cogan-Reese syndrome and essential iris atrophy (see these terms), affecting mainly young adult females and characterized by iris holes and atrophy, papillary distortion, anterior synechiae, corneal edema and often with secondary glaucoma and corneal decompensation as complications
Hepatoportal sclerosis (HPS) is a rare disorder characterized by sclerosis of the intrahepatic portal veins, non-cirrhotic portal hypertension, asymptomatic splenomegaly and recurrent variceal bleeding.
X-linked Charcot-Marie-Tooth disease (CMTX) belongs to the genetically heterogeneous group of CMT peripheral sensorimotor polyneuropathy diseases.
Ataxia with oculomotor apraxia type 2 (AOA2) is a rare autosomal recessive cerebellar ataxia (ARCA; see this term), characterized by progressive cerebellar ataxia associated with frequent oculomotor apraxia, severe neuropathy and an elevated serum alpha-fetoprotein (AFP) level.
Congenital isolated hyperinsulinism (CHI), a rare endocrine disease is the most frequent cause of severe and persistent hypoglycemia in the neonatal period and early infancy and is characterized by an excessive or uncontrolled insulin secretion (inappropriate for the level of glycemia) and recurrent episodes of profound hypoglycemia requiring rapid and intensive treatment to prevent neurological sequelae. CHI comprises 2 different forms: diazoxide-sensitive diffuse hyperinsulinism and diazoxide-resistant hyperinsulinism (see these terms).
Multiple self-healing squamous epithelioma (also known as Ferguson-Smith disease (FSD)) is a rare inherited skin cancer syndrome characterized by the development of multiple locally invasive skin tumors resembling keratoacanthomas of the face and limbs which usually heal spontaneously after several months leaving pitted scars.
Short fifth metacarpals-insulin resistance syndrome is characterised by bilateral shortening of the fifth fingers and fifth metacarpals. It has been described in several members of one family. Some members of the family also had spherocytosis and insulin resistance. Transmission is autosomal dominant.
PANDAS is an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with a group A beta-hemolytic Streptococcal infection and applied to a subgroup of children with obsessive-compulsive disorder (OCD) and/or tic disorders.
Sensorineural hearing loss-early graying-essential tremor syndrome is characterised by the combination of sensorineural hearing loss, early greying of scalp hair and adult onset essential tremor.
Otopalatodigital (OPD) syndrome is a form of frontootopalatodigital syndrome (see this term), characterized by deafness, cleft palate, and characteristic digital anomalies. OPD syndrome is divided into two forms based on severity: the milder form designated OPD type 1 (OPD1), and the more severe and often lethal form designated OPD type 2 (OPD2; see these terms). OPD is an X-linked disorder. Two other genetic disorders with features overlapping OPD, frontometaphyseal dysplasia (FMD) and osteodysplasty, Melnick-Needles type (MNS) have been described; thus OPD1, OPD2, FMD, and MNS are allelic disorders.
Paramyotonia congenita of Von Eulenburg is characterised by exercise- or cold-induced myotonia and muscle weakness. Prevalence is unknown. The syndrome is nonprogressive and is transmitted as an autosomal dominant trait. It is caused by mutations in the gene encoding the alpha subunit of the type IV voltage-gated sodium channel (SCN4A; 17q23.3).
Brachydactyly ('short digits') is a general term that refers to disproportionately short fingers and toes, and forms part of the group of limb malformations characterized by bone dysostosis.
Congenital membranous nephropathy due to maternal anti-neutral endopeptidase (NEP) alloimmunization (CMNEPA) is a glomerular disease characterized by severe renal failure and nephrotic syndrome at birth, which rapidly improve in the first weeks of life.
Intrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder characterized by (i) pruritus with onset in the second or third trimester of pregnancy, (ii) elevated serum aminotransferases and bile acid levels, and (iii) spontaneous relief of signs and symptoms within two to three weeks after delivery.
Hypotrichosis - lymphedema - telangiectasia is an extremely rare syndromic lymphedema disorder characterized by early-onset hypotrichosis, childhood-onset lymphedema, and variable telangiectasia, particularly of the palms.
Bilateral acute depigmentation of the iris (BADI) is characterized by acute onset of bilateral iris depigmentation, pigment dispersion in the anterior chamber, and heavy pigment deposition in the anterior chamber angle. Patients typically present with acute and usually severe photophobia, blurred vision, red eye, and ocular discomfort or pain with a usually self-limiting clinical course. Cases often occur after a flu-like illness, upper respiratory tract infection, and after the use of oral moxifloxacin. When associated with iris epithelial depigmentation, iris transillumination defects and atonic/mydriatic pupil, the condition is referred to as bilateral acute iris transillumination (BAIT) which has an increased risk of severe intractable rise in intraocular pressure.
Adult acute respiratory distress syndrome is a very severe form of acute pulmonary failure secondary to capillary permeability impairment. The symptoms include dyspnea, hypotension and multovisceral failure. The disease is characterized by bilateral pulmonary infiltrates and severe hypoxemia due to increased alveolar-capillary permeability. The severity depends on the degree of alveolar epithelial injury, with a mortality rate of 30-50%.
Infantile apnea is a cessation of respiratory air flow that may affect newborns or older children because of neurological impairment of the respiratory rhythm or obstruction of air flow through the air passages. The symptoms include cyanosis, pallor or bradycardia and snoring in case of obstructive apnea.
Congenital Epstein-Barr virus (EBV) infection causes no clinical manifestations in the majority of infants. Indeed, the occurrence of congenital infection with EBV has never been demonstrated conclusively and must be very rare. One case have been reported to present after birth, multiple congenital anomalies (micrognathia, cryptorchidism, central cataracts), dystrophy, generalized hypotonia, hepatosplenomegaly, diffuse petechiae and hematomas and multiple areas of metaphysitis of the long bones at birth. A low birth weight was also reported. No specific follow-up of the fetus is recommended following maternal EBV primary-infection.
Peters anomaly (PA) is a congenital corneal opacity disorder characterized by a central corneal leukoma that obstructs the pupil leading to visual loss as well as absence of the posterior corneal stroma and Descemet membrane.
Hyperinsulinism due to short chain 3 hydroxylacyl-CoA dehydrogenase (SCHAD) deficiency is a recently described mitochondrial fatty acid oxidation disorder characterized by hyperinsulinemic hypoglycemia with seizures, and in one case fulminant hepatic failure.
Dentinogenesis imperfecta-short stature-hearing loss-intellectual disability syndrome is characterised by the association of dentinogenesis imperfecta, delayed tooth eruption, facial dysmorphology, small stature, sensorineural hearing loss and mild intellectual deficit. It has been described in two brothers born to consanguineous parents. Transmission is autosomal recessive.
Disseminated peritoneal leiomyomatosis (DPL) is characterized by the proliferation of multiple benign smooth muscle cell-containing nodules in the peritoneal cavity.
Familial thrombocytosis is a type of thrombocytosis, a sustained elevation of platelet numbers, which affects the platelet/megakaryocyte lineage and may create a tendency for thrombosis and hemorrhage but does not cause myeloproliferation.
Cancer associated retinopathy (CAR) is a paraneoplastic disease of the eye associated with the presence of extraocular malignancy and circulating autoantibodies against retinal proteins.
Benign paroxysmal torticollis of infancy (BPTI) is a rare functional disorder characterised by recurrent episodes of torticollic posturing of the head (inclination or tilting of the head to one side) in healthy children.
Continuous spikes and waves during sleep (CSWS) is a rare epileptic encephalopathy of childhood characterized by seizures, an electroencephalographic (EEG) pattern of electrical status epilepticus in sleep (ESES) and neurocognitive regression in at least 2 domains of development.
Microscopic polyangiitis (MPA) is an inflammatory, necrotizing, systemic vasculitis that affects predominantly small vessels (i.e. small arteries, arterioles, capillaries, venules) in multiple organs.
Mental retardation-hypotonic facies covers a group of X-linked syndromes characterized by severe intellectual deficit and facial dysmorphism, with variable other features.
Tubular renal disease-cardiomyopathy syndrome is characterised by hypokalaemic metabolic alkalosis secondary to a tubulopathy, hypomagnesaemia with hypermagnesuria, severe hypercalciuria and dilated cardiomyopathy.
Visceral neuropathy-brain anomalies-facial dysmorphism-developmental delay syndrome is characterised by facial dysmorphology, neuropathic visceral dysmotility, neurogenic megacystis, intracerebral calcifications and developmental delay. It has been described in two siblings (brother and sister) born to consanguineous parents. The girl also had microcephaly and multicystic kidneys. The boy had a more extensive neuropathic visceral disorder, leading clinically to chronic intestinal pseudo-obstruction syndrome (CIPO).
Congenital protein C deficiency is an inherited coagulation disorder characterized by deep venous thrombosis symptoms due to reduced synthesis and/or activity levels of protein C.
Oligocone trichromacy is a rare non-progressive form of cone photoreceptor dysfunction characterised by reduced visual acuity, normal retinal appearance, absent or reduced cone responses on electroretinography but normal colour vision.
Goossens-Devriendt syndrome is characterised by intrauterine growth retardation, a congenital heart defect, postaxial polydactyly, a brain malformation, abnormal hair with temporal balding, and marked facial dysmorphism. It has been reported in two siblings from unrelated parents. One of the siblings died and the surviving patient showed postnatal growth retardation and severe developmental delay.
X-linked sideroblastic anemia is a constitutional microcytic, hypochromic anemia of varying severity that is clinically characterized by manifestations of anemia and iron overload and that may respond to treatment with pyridoxine and folic acid.
Tropical endomyocardial fibrosis is a restrictive cardiopathy, occuring almost exclusively in children and young adults in tropical and subtropical regions, characterized by endocardial fibrosis, affecting the apices and the inflow tract of the right or left ventricle (or both) and manifesting with a restrictive cardimyopathy and atrioventricular regurgitation leading to severe pulmonary hypertension, very high systemic venous pressure and congestive cardiac failure. Suspected etiologies include helminth and protozoal infestation and malnutrition.
6q terminal deletion syndrome is marked by a characteristic facial dysmorphism, short neck and psychomotor retardation, generally associated with a range of non-specific malformations.
Schönlein-Henoch purpura (SHP) is a systemic IgA vasculitis that affects small vessels. It is characterized by skin purpura, arthritis, and abdominal and/or renal involvement.
Pyomyositis (PM) is a rare primary bacterial infection of the skeletal muscle, usually resulting from hematogenous spread or due to muscle injury, and characterized by pain and tenderness in the affected muscle, fever and abscess formation.
Aniridia is a congenital ocular malformation characterized by the complete or partial absence of the iris. It can be isolated or part of a syndrome (isolated and syndromic aniridia; see these terms).
Trichorhinophalangeal syndromes (TRPS) type 1 and 3 are malformation syndromes characterized by short stature, sparse hair, a bulbous nasal tip and cone-shaped epiphyses, as well as severe generalized shortening of all phalanges, metacarpals and metatarsal bones.
The association of auricular abnormalities and cleft lip with or without cleft palate has been described in two siblings. One sibling had postauricular pits, profound myopia, nystagmus and retinal pigment abnormalities. The second sibling was a fetus (gestational age: 23 weeks) with severe cleft lip, cleft palate and external ear abnormalities.
, usually acquired through penetration of the skin, (often asymptomatic but that can also manifest with an allergic reaction at the site of skin penetration), followed by the migration of larva through the bloodstream to the lungs (causing asymptomatic pneumonitis, eosinophilia) and finally reaching and colonizing the small intestines where they cause blood extravasation leading to diarrhea, abdominal pain, and when untreated, melena, iron-deficiency anemia and protein malnutrition.
, is a bacterial zoonosis with a wide clinical spectrum that can be life-threatening and, in some cases, can become chronic.
Congenital alpha2 antiplasmin deficiency is a rare hemorrhagic disorder (see this term)caused by congenital deficiency of alpha2 antiplasmin, leading to dysregulated fibrinolysis and is characterized by a hemorrhagic tendency presenting from childhood with prolonged bleeding and ecchymoses following minor trauma and spontaneous bleeding episodes (often in unusual locations like diaphysis of long bones). Congenital alpha2 antiplasmin deficiency is inherited in an autosomal recessive manner.
Juvenile polyposis of infancy (JPI) is the most severe form of juvenile gastrointestinal polyposis (see this term) and is characterized by pancolonic hamartomatous polyposis from stomach to rectum, diagnosed in the first two years of life.
Acquired generalized lipodystrophy belongs to a group of lipodystrophic syndromes characterized by loss of adipose tissue, and is a syndrome of insulin resistance that leads to increased cardiovascular risk. Acquired generalized lipodystrophy is related to a selective loss of subcutaneous adipose tissue occurring exclusively at the extremities (face, legs, arms, palms and sometimes soles).
Hereditary inclusion body myopathy type 3 is characterised by congenital joint contractures (normalizing during early childhood), external ophthalmoplegia, and proximal muscle weakness. In adult cases, the muscular weakness is progressive.
Foix-Alajouanine syndrome, also called subacute ascending necrotising myelitis, results from chronic congestion of the extrinsic pial veins of the spinal cord and of the intrinsic subpial network. It is characterised by progressive ascending deficit over a period of several months or years.
Congenital bile acid synthesis defect type 4 (BAS defect type 4) is an anomaly of bile acid synthesis (see this term) characterized by mild cholestatic liver disease, fat malabsorption and/or neurological disease.
Folinic acid-responsive seizures is a very rare neonatal epileptic encephalopathy disorder characterized clinically by myoclonic and clonic, or clonic seizures associated with apnea occurring several hours to 5 days after birth and responding to folinic acid.
Respiratory bronchiolitis - interstitial lung disease is a mild inflammatory pulmonary disorder developed by cigarette smokers and characterized by shortness of breath and cough, pulmonary function abnormalities of mixed restrictive and obstructive lung disease and high resolution CT scanning showing centrilobular micronodules, ground glass opacities and peribronchiolar thickening.
Sparse hair-short stature-skin anomalies syndrome combines short stature, sparse hair, skin hyperpigmentation and urticaria-like reactions on the hands and arms. An upper central incisor, hypoplastic thumbs and/or palmoplantar hyperkeratosis may also be present. It is thought to be a rare form of ectodermal dysplasia and has been described at least once in a mother and her three sons. Transmission is autosomal dominant, or X-linked.
Hemochromatosis type 2 (juvenile) is the early-onset and most severe form of rare hereditary hemochromatosis (HH; see this term), a group of diseases characterized by excessive tissue iron deposition of genetic origin.
Mild phenylketonuria is a rare form of phenylketouria (PKU, see this term), an inborn error of amino acid metabolism, characterized by symptoms of PKU of mild to moderate severity.
Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type a, or glycogen storage disease (GSD) type 1a, is a type of glycogenosis due to G6P deficiency (see this term).
type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures.
type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by variable biochemical, neurological and hematological manifestations.
Familial LCAT (lecithin-cholesterol acyltransferase) deficiency (FLD) is a form of lecithin-cholesterol acyltransferase deficiency (LCAT; see this term) characterized clinically by corneal opacities, hemolytic anemia, and renal failure, and biochemically by severely decreased HDL cholesterol and complete deficiency of the LCAT enzyme.
Progressive familial intrahepatic cholestasis type 2 (PFIC2), a type of progressive familial intrahepatic cholestasis (PFIC, see this term), is a severe, neonatal, hereditary disorder in bile formation that is hepatocellular in origin and not associated with extrahepatic features. Initially, PFIC2 was reported under the name Byler syndrome.
PFIC1, a type of progressive familial intrahepathic cholestasis (PFIC, see this term), is an infantile hereditary disorder in bile formation that is hepatocellular in origin and associated with extrahepatic features.
Vitamin B12-unresponsive methylmalonic acidemia type mut- is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.
D-2-hydroxyglutaric aciduria (D-2-HGA) is a rare clinically variable neurological form of 2-hydroxyglutaric aciduria (see this term) characterized biochemically by elevated D-2-hydroxyglutaric acid (D-2-HG) in the urine, plasma and cerebrospinal fluid.
Generalized non-Herlitz-type junctional epidermolysis bullosa is a form of non-Herlitz-type junctional epidermolysis bullosa (JEB-nH, see this term) characterized by generalized skin blistering, atrophic scarring, nail dystrophy or nail absence, and enamel hypoplasia, with extracutaneous involvement.
Late-onset junctional epidermolysis bullosa is a subtype of junctional epidermolysis bullosa (JEB, see this term) occurring in childhood or young adulthood.
Severe generalized recessive dystrophic epidermolysis bullosa (RDEB-sev gen) is the most severe subtype of dystrophic epidermolysis bullosa (DEB, see this term), formerly known as the Hallopeau-Siemens type, and is characterized by generalized cutaneous and mucosal blistering and scarring associated with severe deformities and major extracutaneous involvement.
Recessive dystrophic epidermolysis bullosa inversa (RDEB-I) is rare subtype of dystrophic epidermolysis bullosa (DEB, see this term) characterized by blisters and erosions which are primarily confined to intertriginous skin sites, the base of the neck, the uppermost back, and the lumbosacral area.
Oculocutaneous albinism type 1A (OCA1A) is the most severe form of OCA (see this term), where no melanin is produced, and is characterized by white hair and skin, blue, fully translucent irises, nystagmus and misrouting of the optic nerves.
mutations, patients generally exhibit an aged appearance and common age-related disorders at earlier ages compared to the general population.
A, B and C, and salmonelloses themselves.
Punctate palmoplantar keratoderma type I (PPKP1), also known as Buschke-Fischer-Brauer syndrome, is a very rare hereditary skin disease characterized by irregularly distributed epidermal hyperkeratosis of the palms and soles with wide variation among patients..
Mild hyperphenylalaninemia (HPA) is a rare form of phenylketonuria (see this term), an inborn error of amino acid metabolism, characterized by mild symptoms of HPA.
Scleroderma is a rare autoimmune connective tissue disorder characterized by abnormal hardening of the skin and, sometimes, other organs. It is classified into two main forms: localized scleroderma and systemic sclerosis (SSc), the latter comprising three subsets; diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc) and limited SSc (lSSc) (see these terms).
Sialidosis type 1 (ST-1) is a very rare lysosomal storage disease, and is the normosomatic form of sialidosis (see this term), characterized by gait abnormalities, progressive visual loss, bilateral macular cherry red spots and myoclonic epilepsy and ataxia, that usually presents in the second to third decade of life.
Peeling skin syndrome (PSS) refers to a group of rare autosomal recessive forms of ichthyosis (see this term) that is characterized clinically by superficial, asymptomatic, spontaneous peeling of the skin and histologically by a shedding of the outer layers of the epidermis. PSS presents with either an acral (acral PSS) or a generalized distribution (generalized PSS type A (non inflammatory) or B (inflammatory)) (see these terms). Some cases remain difficult to classify, suggesting that there could be additional subtypes of PSS.
Adult-onset Still disease (AOSD) is a rare inflammatory multisystem disorder characterized clinically by fever of unknown origin, arthralgia or arthritis, hyperleucocytosis, and typical skin rash.
Encephalopathy due to sulfite oxidase deficiency is a rare neurometabolic disorder characterized by seizures, progressive encephalopathy and lens dislocation.
Free sialic acid storage disease (free SASD), is a group of lysosomal storage diseases characterized by a spectrum of clinical manifestations including neurological and developmental disorders with severity ranging from the milder phenotype, Salla disease (SD), to the most severe phenotype, infantile free sialic acid storage disease (ISSD).
Regional odontodysplasia (ROD) is a localized developmental anomaly of the dental tissues.
Narcolepsy without cataplexy is characterized by excessive day-time sleepiness associated with uncontrollable sleep urges and sometimes paralysis at sleep, hypnagogic hallucinations and automatic behavior.
Macrostomia-preauricular tags-external ophthalmoplegia syndrome combines macrostomia or abnormal mouth contour, preauricular tags, uni- or bilateral ptosis and external ophthalmoplegia. It was described in nine members of a Brazilian family. It is a new phenotype belonging to the so-called oculoauriculovertebral spectrum, resulting from a branchial arch anomaly. Transmission is autosomal dominant.
PELVIS is an acronym defining the association of Perineal hemangioma, External genitalia malformations, Lipomyelomeningocele, Vesicorenal abnormalities, Imperforate anus, and Skin tag. Eleven cases have been reported.
Idiopathic malabsorption due to increased acid bile synthesis is an intestinal disease of unknown etiology characterized by an overproduction of bile acids which leads to chronic watery diarrhea.
Boichis syndrome consists of the association of congenital nephronophthisis leading to renal failure, and hepatic fibrosis. It has been described in five members of one family, two of whom died from renal failure. The association of Boichis syndrome with tapetoretinal degeneration and intellectual deficit has also been reported in one family: the so-called Senior-Boichis syndrome could be in fact the same entity, and was later reported in a 12 year-old child.
Hinman syndrome (HS) or non-neurogenic neurogenic bladder is a voiding dysfunction of the bladder of neuropsychological origin that is characterized by functional bladder outlet obstruction in the absence of neurologic deficits.
Collagen type III glomerulopathy is a rare glomerular disease characterized by abnormal accumulation of type III collagen within the mesangium and subendothelial space of the glomerulus. Clinically it usually manifests with proteinuria (often in the nephrotic range), microscopic hematuria, peripheral edema and/or hypertension. In some cases progression to end-stage renal failure is observed.
Fibronectin glomerulopathy is a hereditary kidney disease characterized by proteinuria, type IV renal tubular acidosis, microscopic hematuria and hypertension that may lead to end-stage renal failure in the second to sixth decade of life.
Paris-Trousseau thrombocytopenia (TCPT) is a contiguous gene syndrome characterized by mild bleeding tendency, variable thrombocytopenia (THC), dysmorphic facies, abnormal giant alpha-granules in platelets and dysmegakaryopoiesis.
Addison disease (AD) is a chronic and rare endocrine disorder due to autoimmune destruction of the adrenal cortex and resulting in a glucocorticoid and mineralocorticoid deficiency. Properly speaking AD designates autoimmune adrenalitis, but it is a term commonly used to describe any form of chronic primary adrenal insufficiency (CPAI; see this term).
Dysspondyloenchondromatosis is a rare skeletal dysplasia characterized by anisospondyly and multiple enchondromas in vertebrae and the metaphyseal and diaphyseal parts of long tubular bones, leading to kyphoscoliosis and lower limb asymmetry.
Ischio-vertebral syndrome is a very rare, poorly-defined bone disease characterized by ischial aplasia or hypoplasia, vertebral anomalies (vertebral malsegmentation, kyphoscoliosis), and in some patients, non-distinctive facial dysmorphism.
HSD10 disease, atypical type is a clinical subtype of HSD10 disease, a rare neurometabolic disorder. Manifestations may be variable and may be characterized by intellectual disability, choreoathetosis and/or behavior disorders (aggressiveness, agitation, hallucinations, automutilation), as well as pre- and postnatal growth retardation, microcephaly and/or speech impairment. Severe ketoacidosis and elevated urinary excretion of isoleucine metabolites are reported.
X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome is characterized by moderate intellectual deficit, bilateral single palmar creases, seizures, variable hypogammaglobulinemia and characteristic features (synophrys, prognathism, and hirsutism). It has been reported in three males from two generations of one family. All underwent progressive neurological deterioration. This syndrome is transmitted as an X-linked trait, and the causative gene is located between Xq21.33 and Xq23.
X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome is characterised by intellectual deficit, epilepsy, facial dysmorphism and progressive joint contractures. It has been described in two boys. Hypotonia and feeding problems at birth were also reported. The mode of transmission is X-linked.
X-linked intellectual disability, Pai type is characterised by the association of dysmorphism with intellectual deficit. It has been described in four generations of one family. Premature death was reported in the affected males. Transmission is X-linked recessive and the causative gene has been localised to the q28 region of the X chromosome.
, a characteristic face and small teeth. It has been described in four males from two generations of one family. The causative gene appears to be located in the q13 region of the X chromosome.
X-linked intellectual disability, Stoll type is characterised by intellectual deficit, short stature and characteristic facies (hypertelorism, prominent forehead, frontal bossing, a broad nasal tip and anteverted nares). It has been described in four males from three generations of the same family. Two females from this family also displayed intellectual deficit and the characteristic facies. Transmission is X-linked.
X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome is characterised by severe intellectual deficit, hypotonia, mild facial dysmorphism, and aggressive behaviour. It has been described in 10 male members spanning four generations of one family. The facial dysmorphism includes a high forehead, prominent ears, and a small pointed chin. Height and head circumference are reduced. This disorder is transmitted as an X-linked recessive trait and the causative gene maps to Xp22.
X-linked intellectual disability-corpus callosum agenesis-spastic quadriparesis syndrome is characterised by intellectual and motor deficit, spastic quadriparesis and agenesis of the corpus callosum, without craniofacial abnormalities or seizures. It has been described in four male members of a family. The mode of inheritance is most likely X-linked recessive.
X-linked neurodegenerative syndrome, Bertini type is characterised by generalised hypotonia, psychomotor deficit, congenital ataxia and recurrent bronchopulmonary infections. It has been described in seven males from three generations of a family. Five of them died during the first years of life and the remaining patients developed myoclonic encephalopathy and macular degeneration. The locus has been mapped to Xp22.33-pter.
Fried syndrome is a rare X-linked mental retardation (XLMR) syndrome characterized by psychomotor delay, intellectual deficit, hydrocephalus, and mild facial anomalies.
X-linked neurodegenerative syndrome, Hamel type is an X-linked neurodegenerative disorder characterised by intellectual deficit, blindness, convulsions, spasticity, mild hypomyelination and early death. It has been described in about ten male members from two generations of one family. The genetic defect responsible for the disorder is located in the pericentromeric region of the X chromosome, Xp11.3-q12.
#946;2M) deposits in the musculoskeletal system leading to carpal tunnel syndrome (CTS), chronic arthropathy, cystic bone lesions, destructive osteoarthropathy, and pathologic fractures.
Transthyretin (TTR)-related familial amyloidotic cardiomyopathy is a hereditary TTR-related systemic amyloidosis (ATTR) with predominant cardiac involvement resulting from myocardial infiltration of abnormal amyloid protein.
Congenitally uncorrected transposition of the great arteries (congenitally uncorrected TGA), also referred to as complete transposition, is a congenital cardiac malformation characterized by atrioventricular concordance and ventriculoarterial (VA) discordance.
Benign adult familial myoclonic epilepsy (BAFME) is an inherited epileptic syndrome characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course, and no signs of early dementia or cerebellar ataxia.
Nodal marginal zone B-cell lymphoma is a rare, indolent B-cell non-Hodgkin lymphoma, characterized by abnormal clonal proliferation of mature B-lymphocytes with involvement of the lymph nodes, sometimes the bone marrow, and rarely the blood. Clinically it presents with disseminated peripheral, abdominal and/or thoracic lymphadenopathy. Cytopenia and bulky tumors (greater than 5 cm) are rare. Association with Hepatitis C virus and chronic inflammation has been reported.
T-cell large granular lymphocyte leukemia (T-cell LGL leukemia) is a lymphoproliferative malignancy that arises from the mature T-cell (CD3+) lineage.
Aggressive NK-cell leukemia (ANKCL) is an extremely rare and highly aggressive neoplasm, usually manifesting in the third to fourth decade of life, affecting males and females equally, and characterized by the onset of high fever, weight loss, jaundice, skin infiltration, lymphadenopathy, hepatosplenomegaly, and severe anemia. ANKCL has a fulminant and rapidly fatal disease course with the progressive appearance of multiorgan failure and disseminated intravascular coagulation.
Extranodal nasal NK/T cell lymphoma (NKTCL) is a rare, malignant neoplasm mainly affecting men in the fifth decade of life, that usually arises in the nose, paranasal sinuses, orbits or upper airway, and that can present with a nasal mass, nasal bleeding, nasal obstruction, palate perforation (i.e. midline perforation of the hard palate), and mid-facial and/or upper airway destructive lesions. In advanced disease stages, which are associated with a poor prognosis, NKTCL may disseminate to other organs. A few cases of NKTCL presenting primarily in the lymph nodes have also been described.
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL; see this term) characterized histologically by malignant lymphocyte predominant (LP) cells and the absence of typical Hodgkin and Reed-Sternberg (HRS) cells.
Diffuse palmoplantar keratoderma-acrocyanosis syndrome is characterised by the association of diffuse palmoplantar keratoderma and acrocyanosis. It has been described in eight members of one family and in two sporadic cases. The mode of inheritance in the familial cases was autosomal dominant.
Adult heart tumor refers to neoplasms of the heart that manifest in adults and generally present with a variety of non-specific manifestations (depending on tumor site and infiltration) such as weight loss, exhaustion, hemorrhagic pericardial effusion, heart failure, arrhythmias, and embolisms, or that can also be asymptomatic. In adults 75% of heart tumors are benign, with myxoma being the most common benign tumor (accounting for 50-70% of all primary heart tumors) and rhabdomyosarcoma (see this term) comprising 75% of malignant heart tumors. Other malignant tumors of the heart include fibrosarcoma and leiomyosarcoma (see these terms).
Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic.
Endocrine tumours, also referred to as neuroendocrine tumours (NETs), are defined by a common phenotype which is characterized by the expression of general markers (neuron specific enolase, chromogranin, synaptophysin) and hormone secretion products. These tumours may be localized in any part of the body and are generally discovered in non-specific situations, i.e. not immediately suggestive of NETs (tests for inherited predisposition to tumours or for a clinical syndrome caused by abnormal hormone secretion).
Sialidosis type 2 (ST-2) is a rare lysosomal storage disease, and the severe, early onset form of sialidosis (see this term) characterized by a progressively severe mucopolysaccharidosis-like phenotype (coarse facies, dysostosis multiplex, hepatosplenomegaly), macular cherry-red spots as well as psychomotor and developmental delay. ST-2 displays a broad spectrum of clinical severity with antenatal/congenital, infantile and juvenile presentations.
Hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome is characterised by the association of demyelinating leukodystrophy with progressive cerebellar ataxia, hypogonadotropic hypogonadism and hypodontia.
VACTERL/VATER is an association of congenital malformations typically characterized by the presence of at least three of the following: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities.
Waardenburg-Shah syndrome (WSS) is a neurocristopathy characterized by the association of Waardenburg syndrome (sensorineural hearing loss and pigmentary abnormalities; see this term) and Hirschsprung disease (see this term).
KRT14-related epidermolysis bullosa simplex (EBS-AR KRT14) is a basal subtype of epidermolysis bullosa simplex EBS (see this term) characterized by generalized or, less frequently, localized acral blistering.
Centripetalis recessive dystrophic epidermolysis bullosa (RDEB-Ce) is an extremely rare subtype of dystrophic epidermolysis bullosa (DEB, see this term), characterized by blistering which begins acrally and then progressively spreads toward the trunk.
Recessive dystrophic epidermolysis bullosa (RDEB)-generalized other, also known as RDEB non-Hallopeau-Siemens type, is a subtype of DEB (see this term) characterized by generalized cutaneous and mucosal blistering that is not associated with severe deformities.
Infantile Bartter syndrome with deafness, a phenotypic variant of Bartter syndrome (see this term) is characterized by maternal polyhydramnios, premature delivery, polyuria and sensorineural deafness and is associated with hypokalemic alkalosis, increased levels of plasma renin and aldosterone, low blood pressure, and vascular resistance to angiotensin II.
Inflammatory pseudotumor (IPT) of the liver is a rare benign tumor-like lesion.
Paroxysmal cold hemoglobinuria (PCH) is a very rare subtype of autoimmune hemolytic anemia (AIHA, see this term), caused by the presence of cold-reacting autoantibodies in the blood and characterized by the sudden presence of hemoglobinuria, typically after exposure to cold temperatures.
Mixed autoimmune hemolytic anemia is a type of autoimmune hemolytic anemia (AIHA; see this term) defined by the presence of both warm and cold autoantibodies, which have a deleterious effect on red blood cells at either body temperature or at lower temperatures.
Autosomal recessive cutis laxa, type 1 (ARCL1) is a generalized connective tissue disorder characterized by the association of wrinkled, redundant and sagging inelastic skin with severe systemic manifestations (lung atelectesias and emphysema, vascular anomalies, and gastrointestinal and genitourinary tract diverticuli).
Primary intestinal lymphangiectasia (PIL) is a rare intestinal disease characterized by dilated intestinal lacteals which cause lymph leakage into the small bowel lumen. Clinical manifestations include edema related to hypoalbuminemia (protein-losing enteropathy), asthenia, diarrhea, lymphedema and failure to thrive in children.
Secondary intestinal lymphangiectasia is an acquired from of intestinal lymphangiectasia (see this term) manifesting as a protein-losing enteropathy due to another disorder such as Crohn?s disease, congestive heart failure, sarcoidosis, Turner syndrome (see these terms) and often in patients who have undergone a Fontan operation. It is characterized by malabsorption, diarrhea, edema due hypoproteinemia, steatorrhea and serosal effusions.
Scleromyxedema without monoclonal gammopathy is a form of atypical lichen myxedematosus (see this term), characterized by a generalized sclerodermoid infiltration of skin studded with multiple, firm papules of 1-3 mm in diameter involving face (leonine appearance), trunk, and limbs, without monoclonal gammopathy. The involvement of the face can be missing and pruritus may be prominent.
mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome; see these terms) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients.
Hypothyroidism due to thyroid-stimulating hormone (TSH) receptor mutations is a type of primary congenital hypothyroidism (see this term), a permanent thyroid hormone deficiency that is present from birth due to thyroid resistance to TSH.
Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency is a very rare form of congenital adrenal hyperplasia (CAH; see this term) encompassing salt-wasting and non-salt wasting forms with a wide variety of symptoms, including glucocorticoid deficiency and male undervirilization manifesting as a micropenis to severe perineoscrotal hypospadias.
Congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency is a very rare form of congenital adrenal hyperplasia (CAH; see this term) characterized by glucocorticoid deficiency, hypergonadotrophic hypogonadism and severe hypokalemic hypertension.
Osteopenia-myopia-hearing loss-intellectual disability-facial dysmorphism syndrome is characterised by severe hypertelorism, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, osteopaenia with frequent fractures, severe myopia, mild to moderate sensorineural hearing loss and mild intellectual deficit. It has been described in two brothers born to first-cousin parents. No chromosomal anomalies were detected. Transmission appears to be autosomal recessive or X-linked.
Fanconi syndrome (FS) is a generalized disorder of renal proximal tubule function. In adults over 50 years of age, FS is frequently related to the urinary secretion of a monoclonal immunoglobulin (Ig) light chain (LC), almost always of the kappa isotype.
Congenital esophageal diverticulum is a rare, non-syndromic malformation of the esophagus, present at birth, and characterized by a false diverticulum, most often located in the upper, posterior esophagus. Many patients are asymptomatic, but respiratory distress, food regurgitation, dysphagia, chest pain, aspiration pneumonia and discomfort are typical presenting manifestations.
Chronic pneumonitis of infancy is a rare pediatric form of interstitial lung disease (ILD, see this term).
Rieger's anomaly is a congenital ocular defect caused by anterior segment dysgenesis and is characterized by severe anterior chamber deformity with prominent strands and marked atrophy of the iris stroma, with hole or pseudo-hole formation and corectopia. The term covers the association of these iris and pupil anomalies with the features of Axenfeld?s anomaly (see this term).
Familial nasal acilia is a rare genetic otorhinolaryngologic disease characterized by respiratory morbidity due to lack of cilia on the respiratory tract epithelial cells. The disease manifests from birth with respiratory distress, neonatal pneumonia, dyspnea, lobar atelectasis and bronchiectasis. Recurrent infections of the upper and lower respiratory tract, chronic humid coughing, and chronic sinusitis, otitis and rhinitis are typical lifelong presenting conditions.
Renal hypoplasia is a developmental anomaly in which one or both kidneys (unilateral or bilateral renal hypoplasia, respectively (see these terms)) have a deficit in the number of nephrons and may be small. Oligomeganephronia (see this term) represents a severe variant of hypoplasia in which nephron number is reduced by 80% and nephrons are markedly hypertrophied.
Renal cysts and diabetes syndrome (RCAD) is a rare form of maturity-onset diabetes of the young (MODY; see this term) characterized clinically by heterogeneous cystic renal disease and early-onset familial non-autoimmune diabetes. Pancreatic atrophy, liver dysfunction and genital tract anomalies are also features of the syndrome.
Pauci-immune glomerulonephritis (GN) is one of the most frequent causes of rapidly progressive GN (RPGN, see this term). It is characterized clinically by renal manifestations of RPGN (hematuria, hypertension) leading to renal failure within days or weeks, and may be associated with manifestations of systemic vasculitis (arthralgia, fever, seizures, mono neuritis and lung involvement). Pauci-immune GN is histologically characterized by focal necrotizing and crescentic GN, with mild or absent glomerular staining for immunoglobulin and complement by fluorescence microscopy, which may manifest either as part of a systemic small vessel vasculitis (including microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis (see these terms)), or rarely as part of renal-limited vasculitis (RLV, idiopathic crescentic GN). Immunologic classification is based on the presence or absence of circulating anti-neutrophil cytoplasmic antibodies (ANCAs), namely pauci-immune-GN with ANCA and pauci-immune GN without ANCA (see these terms).
Pfeiffer syndrome type 1 (PS1) is a mild to moderately severe type of Pfeiffer syndrome (PS; see this term), characterized by bicoronal craniosynostosis, variable finger and toe malformations, and in most cases, normal intellectual development.
Pfeiffer syndrome type 2 (PS2) is a frequent and severe type of Pfeiffer syndrome (PS; see this term), characterized by cloverleaf skull, severe associated functional disorders, and hand/foot and elbow/knee abnormalities.
Pfeiffer syndrome type 3 (PS3) is a severe type of Pfeiffer syndrome (PS; see this term), characterized by bicoronal craniosynostosis, severe associated functional disorders, and hand, foot and elbow abnormalities.
Autosomal recessive brachyolmia, Maroteaux type is a relatively mild form of brachyolmia (see this term), a group of rare genetic skeletal disorders, characterized by short trunk/short stature, generalized platyspondyly and rounding of vertebral bodies. It remains unknown whether the phenotype represents a single disease entity or a heterogeneous group of mild skeletal dysplasias.
Ulnar hemimelia is a congenital ulnar deficiency of the forearm characterized by complete or partial absence of the ulna bone.
Radial hemimelia is a congenital longitudinal deficiency of the radius bone of the forearm characterized by partial or total absence of the radius.
Fibular hemimelia is a congenital longitudinal limb deficiency characterized by complete or partial absence of the fibula bone.
Brachydactyly type A7 (Smorgasbord type) is a form of brachydactyly that presents with the characteristic features of brachydactyly type A2 (shortening of the middle phalanges of the index finger and, sometimes, of the little finger) and type D (shortening of the distal phalanx of the thumb) plus various additional features.
Genochondromatosis type 2 is a rare genetic bone development disorder characterized by normal clavicles and symmetrical generalized metaphyseal enchondromas particularly in the distal femur, proximal humerus, and bones of the wrists, hands, and feet. Lesions regress later in life with growth cartilage obliteration. Clinical examination is normal and the course of the disease is benign.
Type II mixed cryoglobulinemia, a relatively rare clinico-serological subtype of mixed cryoglobulinemia (MC, see this term), is an immune complex disorder characterized by purpura, weakness and arthralgia and defined immunochemically by cryoglobulins composed of polyclonal IgGs (autoantigens) and monoclonal IgM (autoantibody).
Type III mixed cryoglobulinemia, a relatively rare clinico-serological subtype of mixed cryoglobulinemia (MC, see this term), is an immune complex disorder characterized by purpura, weakness and arthralgia and defined immunochemically by cryoglobulins containing both polyclonal IgGs and polyclonal IgMs.
Dent disease type 1 is a type of Dent disease (see this term) with predominantly renal manifestations.
Juvenile dermatomyositis (JDM) is the early-onset form of dermatomyositis (DM, see this term), a systemic, autoimmune inflammatory muscle disorder, characterized by proximal muscle weakness, evocative skin lesion, and systemic manifestations.
Pediatric Castleman disease (PCD) is a form of Castleman disease (CD, see this term) with a predominant occurrence in teenagers which is either asymptomatic or manifest by systemic (such as fever, anemia, fatigue and failure to thrive) or compressive symptoms.
Localized Castleman disease (LCD) is the most common form of Castleman disease (CD; see this term) and it is usually asymptomatic or it may present with enlarged lymph nodes. LCD may be cured by surgical resection.
Midline interhemispheric variant of holoprosencephaly (MIH) or syntelencephaly is a form of holoprosencephaly (HPE; see this term) characterized by non-separation of the posterior frontal and parietal lobes, normally-formed callosal genu and splenium, absence of the callosal body, normally-separated hypothalamus and lentiform nucleus, and frequent heterotopic gray matter.
Laryngo-tracheo-esophageal cleft (LC) type 1 is a congenital respiratory tract anomaly characterized by a supraglottic, interarytenoid cleft above the vocal folds with moderate respiratory symptoms.
Laryngo-tracheo-esophageal cleft (LC) type 2 is a congenital respiratory tract anomaly characterized by a cleft extending below the vocal folds into the cricoid cartilage, with swallowing disorders and lung infections.
Laryngo-tracheo-esophageal cleft (LC) type 3 is a congenital respiratory tract anomaly characterized by a cleft extending through the cricoid cartilage, sometimes into the cervical trachea, with severe swallowing disorders, lung infections and pulmonary damage.
Laryngo-tracheo-esophageal cleft (LC) type 4 is a serious congenital respiratory tract anomaly characterized by a cleft extending into the thoracic trachea and possibly down to the carina, with respiratory distress.
Hamel cerebro-palato-cardiac syndrome is an X-linked intellectual disability syndrome (XLMR; see this term) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome (see this term).
Golabi-Ito-Hall syndrome is an X-linked intellectual disability syndrome (XLMR; see this term) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome (see this term).
Holmes-Gang syndrome is an X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies; see this term).
Chudley-Lowry syndrome is an X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation-hypotonic facies; see this term).
Carpenter-Waziri syndrome is an X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies; see this term).
Renier-Gabreels-Jasper syndrome is an X-linked mental retardation (XLMR) syndrome belonging to the group of conditions characterised by the association of intellectual deficit with hypotonic facies (Mental retardation, X-linked-hypotonic facies; see this term).
gene: mutations in this gene have already been implicated in osteopoikilosis.
Severe intellectual disability-epilepsy-anal anomalies-distal phalangeal hypoplasia is characterised by severe intellectual deficit, epilepsy, hypoplasia of the terminal phalanges, and an anteriorly displaced anus. It has been described in two sisters born to consanguineous parents. The syndrome is transmitted as an autosomal recessive trait and appears to be caused by anomalies in to chromosome regions, one localised to chromosome 1 and the other to chromosome 14.
Hereditary renal hypouricemia (HRH) is a rare autosomal recessively inherited renal membrane transport disorder affecting urate reabsorption in the proximal tubules leading to usually asymptomatic hypouricemia and predisposing to urolithiasis and exercise induced acute renal failure (EIARF).
Pseudohypoparathyroidism type 2 (PHP2) is a type of pseudohypoparathyroidism (PHP; see this term) characterized by resistance to parathyroid hormone (PTH), which manifests with hypocalcemia, hyperphosphatemia and elevated PTH levels, absence of Albright's hereditary osteodystrophy (AHO; see this term), and normal expression of the Gs protein with a normal urinary cAMP response.
Autosomal dominant cerebellar ataxia (ADCA) type I is a group of spinocerebellar ataxias (SCAs) characterized by ataxia with other neurological signs, including oculomotor disturbances, cognitive deficits, pyramidal and extrapyramidal dysfunction, bulbar, spinal and peripheral nervous system involvement.
Autosomal dominant cerebellar ataxia (ACDA; see this term) type III is a group of neurodegenerative disorders characterized by mostly pure cerebellar syndromes with occasional non-cerebellar signs (e.g. pyramidal signs, peripheral neuropathy, writer's cramp) and includes spinocerebellar ataxia (SCA) type 5 (SCA5), SCA6, SCA11, SCA26, SCA30, and SCA31 (see these terms).
Hepatoerythropioetic porphyria (HEP) is a very rare form of chronic hepatic porphyria (see this term) characterized by bullous photodermatitis.
Secondary short bowel syndrome is an intestinal failure caused by any condition that results in a functional small intestine of less than 200 cm in length and is characterized by diarrhea, nutrient malabsoption, bowel dilation and dysmobility.
Twin twin transfusion syndrome (TTTS) is a rare condition seen in twin monochorionic pregnancies, typically developing during the 15-26 week gestation period and usually due to unbalanced intertwin placental anastomoses, where an unequal exchange of blood between twins causes oligohydramnios in one sac and polyhydramnios in the other which can lead to a high perinatal mortality rate and a high rate of disability in survivors if left untreated
Acroosteolysis dominant type (AOD) is a rare genetic osteolysis syndrome characterized by acroosteolysis of distal phalanges and generalized osteoporosis, associated with additional ossification anomalies, craniofacial dysmorphism, dental anomalies and a wide range of other characteristics.
Acro-pectoro-renal field defect is a very rare association of a Poland anomaly (see this term), that is characterized by unilateral absence or hypoplasia of the pectoralis major muscle (most frequently involving the sternocostal head) and a variable degree of ipsilateral hand anomalies (including symbrachydactyly, brachydactyly, absent thumb and hypoplastic fingers), combined with a genito-urinary anomaly. Associated genito-urinary anomalies reported include renal hypoplasia or agenesis, duplex collecting system, ureteropelvic junction obstruction, hypospadias and undescended testicles.
Congenital adrenal hyperplasia due to cytochrome P450 oxidoreductase deficiency is a unique form of congenital adrenal hyperplasia (CAH; see this term) characterized by glucocorticoid deficiency, severe sexual ambiguity in both sexes and skeletal (especially craniofacial) malformations.
Athyreosis is a form of thyroid dysgenesis (see this term) characterized by complete absence of thyroid tissue that results in primary congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth.
Familial thyroid dyshormonogenesis is a type of primary congenital hypothyroidism (see this term), a permanent thyroid hormone deficiency that is present from birth, which results from inborn errors of thyroid hormone synthesis.
related disorders including Okihiro syndrome and Holt-Oram syndrome (see these terms). Transmission is autosomal dominant.
4p16.3 microduplication syndrome is a rare genetic syndrome that results from the partial duplication of the short arm of chromosome 4. It has a highly variable phenotype, principally characterized by psychomotor and language delay, seizures and dysmorphic features such as high forehead with frontal bossing, hypertelorism, prominent glabella, long narrow palpebral fissures, low set ears and short neck. Eye abnormalities (glaucoma, irregular iris pigmentation, hyperopia) have also been reported.
8p inverted duplication/deletion [invdupdel(8p)] syndrome is a rare chromosomal anomaly characterized clinically by mild to severe intellectual deficit, severe developmental delay (psychomotor and speech development), hypotonia with tendency to develop progressive hypertonia and severe orthopedic problems over time, minor facial anomalies and agenesis of the corpus callosum.
Distal trisomy of the long arm of chromosome 10 (10q) is characterized by pre- and postnatal growth retardation, a pattern of specific facial features, hypotonia, and developmental and psychomotor delay.
Hereditary sensory and autonomic neuropathy, type 2 (HSAN2) is an inherited disorder characterized by profound and universal sensory loss involving large and small fiber nerves, and marked hypotonia.
and Nesprin-1-related CMD; see these terms).
Rigid spine syndrome (RSS) is a slowly progressive childhood-onset congenital muscular dystrophy (see this term) characterized by contractures of the spinal extensor muscles associated with abnormal posture (limitation of neck and trunk flexure), progressive scoliosis of the spine, early marked cervico-axial muscle weakness with relatively preserved strength and function of the extremities and progressive respiratory insufficiency.
6cm and approximately 1/3 have metastasized at the time of diagnosis. It often co-occurs with Zollinger-Ellison syndrome or multiple endocrine neoplasia type 1 (MEN 1; see these terms).
PPoma is a type of pancreatic endocrine tumor (see this term) that hypersecretes pancreatic polypeptide (PP) but that does not cause a hypersecretion syndrome (is non-functioning) and instead presents with only non-specific symptoms such as weight loss, abdominal pain, jaundice, diarrhea and/or an abdominal mass, hence leading to a late diagnosis. PPoma can be associated with multiple endocrine neoplasia 1 (MEN-1; see this term).
VIPoma is an extremely rare type of pancreatic neuroendocrine tumor (see this term) that secretes vasoactive intestinal polypeptide (VIP) leading to the manifestations of watery diarrhea, hypokalemia and achlorhydia or hypochhlorhydia (known as WDHA syndrome).
Thymic endocrine tumor is a rare, malignant, primary thymic neoplasm originating from neuroendocrine cells, presenting as a mass within the anterior mediastinum. Patients typically present with nonspecific symptoms, such as chest pain, cough, shortness of breath, or in some cases, superior vena cava syndrome, although patients could be asymptomatic during the early stages or present with multiple endocrine neoplasia type I. Ectopic production of ACTH and serotonin can lead to Cushing syndrome and carcinoid sydrome, respectively.
Unilateral adactylia is a terminal transverse defect of the hand characterized by the absence of the terminal portions of digits 2 to 5 with a hypoplastic thumb (adactylia).
Panner's disease is an osteochondrosis of the capitellum of the humerus, characterised by involvement of the dominant upper limb and onset before the age of 10 years. It results from lateral compression injuries of the elbow typically occurring in children practising sports such as baseball and throw. It should be distinguished from osteochondritis dissecans of the capitellum (see this term), occurring later, in adolescents. Management is symptomatic and consists in reducing the activities of the affected elbow for a prolonged period of time. Prognosis is good.
Sinding-Larsen-Johansson disease is a type of osteochondrosis affecting the attachment of the patellar tendon to the patella and characterised by tenderness and localized swelling of the patella.
Persistent placoid maculopathy is characterised by white plaque-like lesions involving the macula but sparing the peripapillary areas of both eyes. It has been described in five patients. In contrast to patients with macular serpiginous choroiditis presenting with similar lesions, the five patients reported so far with persistent placoid maculopathy had good visual acuity until the onset of choroidal neovascularization (CNV) or pigmentary mottling. The macular lesions fade after several months or years, but the vascular anomalies persist leading to a loss of central vision.
Parkinsonism with dementia of Guadeloupe is characterised by symmetrical bradykinesia, predominantly axial rigidity, postural instability with early falls and cognitive decline with prominent features of frontal lobe dysfunction.
Bilateral multicystic dysplastic kidney (MCDK) is a lethal form of multicystic dysplastic kidney (MCDK, see this term), a congenital anomaly of the kidney and urinary tract (CAKUT), in which both kidneys are large, distended by non-communicating multiple cysts and non-functional.
'Renal tubular dysgenesis due to twin-twin transfusion syndrome (TTTS; see this term) is an acquired form of renal tubular dysgenesis (see this term) that develops in donor fetuses due to the uneven shunting of growth factor and nutrients to the kidney of the recipient and is characterized by absent or poorly developed proximal tubules, persistent oligohydramnios and consequently the Potter sequence (facial dysmorphism with large and flat low-set ears, lung hypoplasia, arthrogryposis and limb positioning defects).'
Pauci-immune glomerulonephritis (GN) with antineutrophil cytoplasmic antibodies (ANCA) is a form of rapidly progressive GN comprising about 90% of pauci-immune glomerulonephritis (see this term), and associated with the presence of circulating ANCA (mostly directed against proteinase-3 (PR3) and myeloperoxidase (MPO)). Patients usually present with hematuria and rapidly declining renal function, often leading to dialysis within weeks without treatment. Cutaneous, pulmonary, musculoskeletal and nervous involvement may be observed in case of systemic disease, and the correlation between ANCA titer and disease activity has been demonstrated.
Pauci-immune glomerulonephritis (GN) without antineutrophilic cytoplasmic antibodies (ANCA) is a form of rapidly progressive glomerulonephritis comprising 10-43% of pauci-immune glomerulonephritis (see this term) and characterized by the absence of ANCA. In comparison with pauci-immune GN with ANCA (see this term), patients lacking ANCA may be younger at onset of the disease and have a shorter interval from onset of the disease to diagnosis. They have fewer extra renal manifestations (e.g. involvement of lung, eye, ear, nose and throat), fewer constitutional symptoms (e.g. fever, weight loss, muscle pain and arthralgia) and a high prevalence of nephrotic syndrome and chronic renal lesions. Their prognosis is generally poorer.
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive (AR) disorder characterized by the formation and hyperexcretion of 2,8-dihydroxyadenine (2,8-DHA) in urine, causing urolithiasis and crystalline nephropathy.
17q11 microdeletion syndrome is a rare severe form of neurofibromatosis type 1 (NF1; see this term) characterized by mild facial dysmorphism, developmental delay, intellectual disability, increased risk of malignancies, and a large number of neurofibromas.
Peripheral resistance to thyroid hormones may be a cause of permanent congenital hypothyroidism (see this term), a permanent thyroid hormone deficiency that is present from birth.
Unilateral absence of the pulmonary artery (UAPA) is a rare congenital great vessels anomaly that commonly presents by dyspnea, frequent respiratory infections, hemoptysis and high-altitude pulmonary edema. UAPA is often associated with congenital heart malformation (CHM, see this term). In the absence of associated cardiac malformation (isolated UAPA; IUAPA), the condition may be asymptomatic until adult age.
Internal carotid artery (ICA) agenesis (uni or bilateral) is a developmental defect that may be asymptomatic or lead to cerebrovascular lesions. It is a rare malformation, with only around hundred cases reported in the literature. When symptoms are present, they are caused by cerebrovascular insufficiency, compression of the brain by vessels that dilate to compensate for the absence of the ICA, or the presence of an aneurysm. Associated intracranial aneurysms occur in 25 to 35% of patients and are often responsible for intracranial hemorrhage, which may present as the initial symptom. The absence of the ICA is the result of either agenesis or aplasia. The term agenesis is used when both the ICA and its bony canal are absent, whereas there is some evidence of carotid canals in cases of aplasia. The absence of the ICA can be detected by angiography or by computerised tomography.
Pulmonary valve agenesis is a rare congenital heart malformation characterized by a total or partial absence of the pulmonary valve leaflets associated with stenosis of the pulmonary artery orifice and aneurysmal dilatation of the pulmonary arteries. It usually occurs in association with additional cardiovascular malformations such as teralogy of fallot or ventricular septal defect, or can occur as part of a syndrome (e.g. 22q11.2 deletion syndrome; see this term). Clinical features depend on the presence of associated cardiac malformations and include pulmonary insufficiency, bronchial obstruction (secondary to compression by aneurysmally dilated pulmonary arteries), pulmonary stenosis, cyanosis, and cardiac failure.3424
Secondary polycythemia is an elevated absolute red blood cell mass caused by enhanced stimulation of red blood cell production by an otherwise normal erythroid lineage that may be congenital or acquired (congenital secondary polycythemia and acquired secondary polycythemia; see these terms).
Autosomal dominant dopa-responsive dystonia (DYT5a) is a rare neurometabolic disorder characterized by childhood-onset dystonia that shows a dramatic and sustained response to low doses of levodopa (L-dopa) and that may be associated with parkinsonism at an older age.
Unclassified myelodysplastic syndrome (MDS-U) is a subtype of myelodysplastic syndrome (MDS; see this term) with atypical features of uncertain clinical significance.
Primary mediastinal B-cell lymphoma (PMBL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL; see this term), arising from B cells of thymic origin, that affects mainly women between the ages of 20-30, that usually presents with a bulky and rapidly expanding anterior mediastinal mass, often with pleural and pericardial effusions, and that can invade the lungs, superior vena cava, pleura, pericardium, and chest wall, leading to manifestations of cough, dyspnea, and superior vena cava syndrome.
Intravascular large B-cell lymphoma (IVLBCL) is a very rare form of diffuse large B-cell lymphoma (see this term) characterized by the selective growth of lymphoma cells within the lumina of small blood vessels (especially the capillaries) that most often presents with a wide range of clinical manifestations (as potentially any tissue can be involved), with patients from Western countries more frequently manifesting with neurological and cutaneous symptoms while patients from Asian countries more frequently displaying hepatosplenomegaly and thrombocytopenia. IVLBCL is characterized by an absence of lymphadenopathy, an aggressive clinical course and a poor prognosis.
Southeast Asian ovalocytosis (SAO) is a rare hereditary red cell membrane defect characterized by the presence of oval-shaped erythrocytes and with most patients being asymptomatic or occasionally manifesting with mild symptoms such as pallor, jaundice, anemia and gallstones.
Hemophilia A is the most common form of hemophilia (see this term) characterized by spontaneous or prolonged hemorrhages due to factor VIII deficiency.
Familial dysfibrinogenemia is a coagulation disorder characterized by a bleeding tendency due to a functional anomaly of circulating fibrinogen.
Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is an inflammatory neuropathy belonging to the clinical spectrum of Guillain-Barré syndrome (GBS; see this term).
Acute motor-sensory axonal neuropathy (AMSAN) is a motor-sensory, axonal form of Guillain-Barré syndrome (GBS; see this term).
Acute motor axonal neuropathy (AMAN) is a pure motor axonal form of Guillain-Barré syndrome (GBS; see this term).
Multiple system atrophy, parkinsonian type (MSA-p) is a form of multiple system atrophy (MSA; see this term) with predominant parkinsonian features (bradykinesia, rigidity, irregular jerky postural tremor, and postural instability).
Inverse Marcus-Gunn phenomenon is a rare congenital synkinesis where jaw opening by the pterygoid muscle (during eating or yawning) causes eyelid drooping from inhibition of the oculomotor nerve to the levator palpebrae superioris. Familial occurrence has been reported.
Chandler syndrome, the most frequent clinical variant of iridocorneal endothelial (ICE) syndrome (see this term), is characterized by very few iris abnormalities but more severe corneal edema and less severe secondary glaucoma than seen in the other two ICE syndrome variants: Cogan-Reese syndrome and essential iris atrophy (see these terms).
Essential iris atrophy is a clinical variant of iridocorneal endothelial (ICE) syndrome (see this term), characterized by progressive iris atrophy and holes present on the surface of the iris, corneal edema, corectopia, uveal ectropion and anterior synechiae. Secondary glaucoma is also a common complication of the disease.
Agnathia-holoprosencephaly-situs inversus syndrome is an extremely rare and fatal association syndrome, characterized by absence of the mandible, cerebral malformations with facial anomalies related to a defect in cleavage in the embryonic brain (e.g. synophthalmia, malformed and low-set ears fused in midline (otocephaly), agenesis of the olfactory bulbs, microstomia, hypoglossia/aglossia) and situs inversus partialis or totalis.
Butterfly-shaped pigment dystrophy is a patterned dystrophy of the retinal pigment epithelium (see this term) characterized by abnormal accumulation of lipofuscin in a butterfly-shaped distribution at the retinal pigment epithelium level. Patients manifest with a slowly progressive loss of vision that often only becomes apparent in old age.
Multifocal pattern dystrophy simulating fundus flavimaculatus is a patterned dystrophy of the retinal pigment epithelium (see this term) characterized by multiple yellowish irregular flecks scattered or interconnected around the macula, simulating what is observed in Stargardt disease (see this term), and usually asymptomatic until adulthood when patients present with a slowly progressive loss of vision that often only becomes apparent in old age.
Total pulmonary venous return (TAPVR) is a form of congenital pulmonary venous return (see this term)where all of the pulmonary veins drain into the right atrium or one of its tributaries, instead of the left atrium, leading to various manifestations such as fatigue, exertional dyspnea, pulmonary arterial hypertension, cyanosis and progressive congestive heart failure.
Congenital complete agenesis of pericardium is a rare, mostly asymptomatic, congenital heart malformation characterized by the complete absence of the entire pericardium, or by the absence of either the right (uncommon) or left pericardium. It is occasionally associated with chest pain (common), dyspnea, dizziness, bradycardia and syncope, while exertional manifestations are rare. The disease is usually incidentally diagnosed during surgery or at autopsy.
Congenital partial agenesis of pericardium is a rare, mostly asymptomatic, congenital heart malformation mainly characterized by the partial absence of the left pericardium. It is occasionally associated with chest pain or dyspnea and is usually incidentally diagnosed during surgery or at autopsy. Herniation and strangulation of a portion of the heart through the pericardial foramen may occur, resulting in myocardial acute ischemia and possible sudden death. Right side pericardium involvement is rare.
Pleuro-pericardial cyst is a rare, mostly congenital, pericardium anomaly characterized by the presence of, usually asymptomatic, cysts which are typically located in the right costophrenic angle and are usually incidentally diagnosed. On occasion, it manifests with chest pain, dyspnea, tachycardia, persistent cough or cardiac arrhythmias. The condition is usually benign, but rare complications, such as cardiac tamponade, cardiogenic shock, mitral valve prolapse, hoarseness atrial fibrillation, right ventricular outflow, tract obstruction, spontaneous internal hemorrhage, pulmonary stenosis and sudden death, may occur.
Hemolytic anemia due to erythrocyte adenosine deaminase overproduction is a rare, genetic, hematologic disease characterized by mild, chronic hemolytic anemia (due to highly elevated adenosine deaminase activity in red blood cells resulting in their premature destruction), elevated reticulocyte count, splenomegaly and mild hyperbilirubinemia. Other cells and tissues are not affected.
Tarsal kink syndrome is a rare congenital malformation of the tarsus that causes entropion characterized by blepharospasm and absence of an upper eyelid fold that may lead to corneal ulceration caused by the folded edge of the upper tarsus or the inturned eyelashes if not corrected by surgery.
Euryblepharon is a rare congenital eyelid anomaly of unknown etiology characterized by the bilateral horizontal enlargement of the palpebral fissure with vertically shortened eyelids, lateral canthus malpositioning and lateral ectropion. It may be isolated or associated with other ocular anomalies (e.g. strabismus or telecanthus; see this term) or systemic anomalies (e.g. blepharo-cheilo-odontic syndrome, see this term). In severe cases, it may result in lagophthalmos and exposure keratopathy, requiring surgical treatment.
48,XYYY syndrome is a rare Y chromosome number anomaly that affects only males and is characterized by mild-moderate developmental delay (especially speech), normal to mild intellectual disability, large, irregular teeth with poor enamel, tall stature and acne. Radioulnar stenosis and clinodactyly have also been associated. Boys generally present normal genitalia, while hypogonadism and infertility is frequently reported in adult males.
49,XYYYY is a rare Y chromosome number anomaly with a variable phenotype mainly characterized by moderate to severe intellectual disability, speech delay, hypotonia, and mild dysmorphic features, including facial asymmetry, hypertelorism, bilateral low set 'lop' ears, and micrognatia. Skeletal abnormalities (such as skull deformities, radioulnar synostosis, elbow flexion, clinodactyly, brachydactyly) and behavourial problems have also been associated with this condition. Genitalia are normal at birth, although hypogonadism and azoospermia has been reported in adults.
Myotonia permanens is a very rare, persistent and more severe form of potassium-aggravated myotonia (PAM, see this term).
Acetazolamide-responsive myotonia is a form of potassium-aggravated myotonia (PAM, see this term) which shows dramatic improvement with the use of acetazolamide (ACZ).
Oligodontia is a rare developmental dental anomaly in humans characterized by the absence of six or more teeth.
Turcot syndrome with polyposis or Turcot syndrome type 2 is a form of familial adematous polyposis, characterized by the concurrence of thousands of colonic adenomatous polyposis or colorectal cancer (CRC) and a primary central nervous system tumor (principally medulloblastoma). It is also associated with pigmented ocular fundus lesions.
Nipah virus disease, caused by the Nipah virus, is a recently discovered zoonotic disease characterized by fever, constitutional symptoms and encephalitis, sometimes accompanied by respiratory illness.
Resistance to thyrotropin-releasing hormone (TRH) syndrome is a type of central congenital hypothyroidism (see this term) characterized by low levels of thyroid hormones due to insufficient release of thyroid-stimulating hormone (TSH) caused by pituitary resistance to TRH. It may or may not be observed from birth.
Genetic recurrent myoglobinuria is an inborn error of metabolism characterized by abnormal urinary excretion of myoglobin due to acute destruction of skeletal muscle fibers.
Ravine syndrome is an extremely rare genetic neurological disorder, reported in a small number of patients in a specific community on Reunion Island (Ravine region), characterized by infantile anorexia with irrepressible and repeated vomiting, acute brainstem dysfunction, severe failure to thrive, and progressive encephalopathy with MRI showing vanishing of medulla oblongata and cerebellar white matter and severe atrophy of pons, along with supra-tentorial periventricular white-matter hyperintensities and basal ganglia anomalies.
Thymic carcinoma (TC) is a type of thymic epithelial neoplasm (see this term) characterized by a high malignant potential.
Thymic neuroendocrine carcinoma is a type of thymic epithelial neoplasm (see this term) displaying evidence of neuroendocrine differentiation.
Cushing syndrome due to ectopic (adrenocorticotropic hormone) ACTH secretion (EAS) is a form of ACTH-dependent Cushing syndrome (see this term) caused by excess secretion of ACTH by a benign or, more often, malignant non-pituitary tumor.
Adrenocorticotropic hormone (ACTH) independent Cushing syndrome is a form of endogenous Cushing syndrome (CS; see this term) that may result from excess secretion of cortisol by either a unilateral and benign (adrenocortical adenoma: 55-60%) or malignant (adrenocortical carcinoma: 35-40 %) adrenocortical tumor or by bilateral adrenal secretion by macronodular adrenal hyperplasia (AIMAH), as an isolated disease or as part of McCune-Albright syndrome (MAS), or by primary pigmented nodular adrenocortical disease (PPNAD), as an isolated disease or as part of Carney complex (CNC; see these terms).
and is transmitted to humans through the bites and scratches of infected rats.
House allergic alveolitis is a hypersensitivity pneumonitis (see this term) resulting from the inhalation of an antigen to which an individual has been previously sensitized in his/her domestic environment. House allergic alveolitis encompasses summer hypersensitivity pneumonitis, humidifier-induced lung diseases, hot tub lung and legionellosis (see this term).
Malignant dysgerminomatous germ cell tumor of ovary is the most common form of malignant germ cell tumor of ovary (see this term), arising from germ cells in the ovary, usually presenting during adolescence with pelvic mass, fever, vaginal bleeding, and acute abdomen and is characterized by bilaterality (around 10% of cases), association with dysgenetic gonads (5 to 10% of cases), elevated serum lactate dehydrogenase (LDH) and human chorionic gonadotrophin (hCG) (in the presence of syncitiotrophoblasts). Malignant dysgerminomatous germ cell tumor of ovary responds well to chemotherapy, potentially sparing patients from infertility and early mortality.
Malignant granulosa cell tumor of ovary is a rare malignant sex cord stromal tumor of ovary (see this term) arising from the granulosa cells of the ovary, which occurs in peri and post menopausal women, and that presents with abnormal vaginal bleeding, abdominal pain and distension. The tumor is frequently unilateral, estrogen secreting, and has a slow natural history and a tendency to relapse long after the initial diagnosis, necessitating prolonged follow-up.
Malignant Sertoli-Leydig cell tumor of ovary is a rare malignant sex cord stromal tumor of ovary (see this term) occuring typically in young women and characterized by manifestations of androgen excess (hirsutism, hair loss, amenorrhea, or oligomenorrhea), when functional.
Malignant steroid cell tumor of the ovary, not otherwise specified is a rare malignant sex cord stromal tumor of ovary (see this term) of unknown histological lineage, occurring in adult women, characterized, in most cases, by manifestations of androgen excess (hirsutism, hair loss, amenorrhea, or oligomenorrhea) and, occasionally, Cushing syndrome (see this term).
Secondary pulmonary hemosiderosis is a respiratory disease due to the deposition of hemosiderin-laden macrophages in lungs as a result of repeated alveolar hemorrhage secondary to another disease, especially dysimmunitary disorders (i.e. Heiner syndrome (see this term), autoimmune diseases), thrombotic disorders and cardiovascular disorders such as mitral stenosis. It manifests as a triad of hemoptysis, anemia and diffuse parenchymal infiltrates on chest radiography
Heiner syndrome, also called cow's milk hypersensitivity, is a food induced pulmonary hypersensiting syndrome that affects primarily infants and that is characterized by pulmonary hemosiderosis (see this term), digestive bleeding, anemia and poor growing, improving with elimination of cow's milk from the diet.
Autosomal dominant Charcot-Marie-Tooth disease type 2I (CMT2I) is a form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by a late onset with severe sensory loss (paresthesia and hypoesthesia) associated with distal weakness, mainly of the legs, and absent or reduced deep tendon reflexes.
Autosomal dominant Charcot-Marie-Tooth disease, type 2K (CMT2K) is an axonal CMT peripheral sensorimotor polyneuropathy.
Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant central nervous system (CNS) rhabdoid tumor (RT; see this term) found almost exclusively in children.
Intermediate DEND syndrome (iDEND) is a rare mild form of DEND syndrome (see this term), a neonatal diabetes mellitus, developmental delay and epilepsy condition. The intermediate form is characterized clinically by mild motor, speech or cognitive delay and an absence of epilepsy.
Isolated hyperchlorhidrosis is characterized by the excessive loss of salt (sodium chloride or NaCl) in sweat. In particular, ""hyperchlorhidrosis"" refers to the high levels of chloride found in sweat, although both sodium and chloride are released. Because the salt is abnormally released from the body in sweat, there are lower than normal levels of sodium in fluids inside the body (hyponatremia). Most infants with isolated hyperchlorhidrosis experience one or more episodes of dehydration with low levels of sodium in the blood (hyponatremic dehydration), which can require hospitalization. These episodes typically follow a mild illness that causes vomiting or diarrhea. Affected infants also have poor feeding and an inability to grow and gain weight at the expected rate (failure to thrive). By early childhood, though, weight and height usually catch up to normal, although the abnormal loss of salt still remains. These individuals may still experience dangerous hyponatremia when they sweat excessively, for example in warm temperatures or when exercising.While hyperchlorhidrosis can occur as one of several features of other conditions, such as cystic fibrosis, people with isolated hyperchlorhidrosis do not have the additional signs and symptoms of these other conditions.
Carisoprodol is a centrally acting muscle relaxant used to relieve acute back pain. Due to the risk of dependence and abuse, carisoprodol should only be used for treatment periods of up to two or three weeks. Carisoprodolol is a Schedule IV controlled substance and carisoprodol overdose can lead to CNS respiratory depression, seizures, and death. Carisoprodol is metabolized by CYP2C19 to meprobamate, a sedative used to treat anxiety disorders. In individuals who have little or no CYP2C19 activity (“CYP2C19 poor metabolizers”), standard doses of carisoprodol can lead to a 4-fold increase in exposure to carisoprodol and a concomitant 50% reduced exposure to meprobamate compared to normal metabolizers. Approximately 3-5% of Caucasians and Africans, and 15-20% of Asians, are CYP2C19 poor metabolizers. The FDA-approved drug label for carisoprodol states that caution should be used when administering carisoprodol to patients with reduced CYP2C19 activity and when co-administering drugs that inhibit or induce CYP2C19. There are no data on the use of carisoprodol in pregnancy, and the efficacy, safety, and pharmacokinetics of carisoprodol have not been established in pediatric patients (less than 16 years of age).
Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of major depressive and anxiety disorders, and may be used to treat other psychiatric conditions. Fluvoxamine is metabolized by cytochrome P450 2D6 (CYP2D6) and variations in CYP2D6 may affect drug exposure. CYP2D6 poor metabolizers showed greater drug exposure to fluvoxamine compared to extensive metabolizers at similar drug doses while data are lacking describing the effect of CYP2D6 ultrarapid metabolism on fluvoxamine therapy. Therapeutic guidelines for the SSRI fluvoxamine based on CYP2D6 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of major depressive and anxiety disorders, and may be used to treat other psychiatric conditions. Paroxetine is extensively metabolized by cytochrome P450 2D6 (CYP2D6) and variations in CYP2D6 may affect drug exposure. CYP2D6 ultrarapid metabolizers might have lower or undetectable paroxetine plasma concentrations while CYP2D6 poor metabolizers showed greater drug exposure to paroxetine compared to extensive metabolizers at similar drug doses. Therapeutic guidelines for the SSRI paroxetine based on CYP2D6 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Imipramine is a tricyclic antidepressant used in the treatment of several psychiatric disorders including major depression, obsessive-compulsive disorder, generalized anxiety disorder, post-traumatic stress disorder, and bulimia. Imipramine may also be useful as an adjunctive treatment in the management of panic attacks, neuropathic pain, attention-deficit disorder, and childhood enuresis (bedwetting). Tricyclic antidepressants (TCAs) primarily mediate their therapeutic effect by inhibiting the reuptake of both serotonin and norepinephrine, leaving more neurotransmitter in the synaptic cleft stimulating the neuron. Because tricyclics can also block different receptors (histamine H1, a1-adrenergic, and muscarinic receptors), side effects are common. As such, more specific selective serotonin reuptake inhibitors (SSRIs) have largely replaced the use of them. However, TCAs still have an important use in specific types of depression and other conditions. Imipramine is primarily metabolized via CYP2C19 to active metabolites, including desipramine, also a tricyclic antidepressant. Further metabolism is catalyzed by CYP2D6. Individuals who are ""CYP2D6 ultrarapid metabolizers"" carry more than two normal function alleles (i.e., multiple copies), whereas individuals who are ""CYP2C19 ultrarapid metabolizers"" carry two increased function alleles. Individuals who are CYP2D6 or CYP2C19 ""poor metabolizers"" carry two no function alleles for CYP2D6 or CYP2C19, respectively. The FDA-approved drug label for imipramine states that CYP2D6 poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants when given usual doses. Their recommendations include monitoring tricyclic antidepressant plasma levels whenever a tricyclic antidepressant is going to be co-administered with another drug known to be an inhibitor of CYP2D6. In 2016, the Clinical Pharmacogenetics Implementation Consortium (CPIC) made dosing recommendations for tricyclic antidepressants based on CYP2C19 and CYP2D6 genotypes. Amitriptyline and nortriptyline were used as model drugs for this guideline because the majority of pharmacogenomic studies have focused on these two drugs. According to the CPIC guideline, because TCAs have comparable pharmacokinetic properties, it may be reasonable to apply the recommendations to other tricyclics, including imipramine. For CYP2D6 ultrarapid metabolizers, CPIC recommends avoiding the use of a tricyclic due to the potential lack of efficacy, and to consider an alternative drug not metabolized by CYP2D6. If a TCA is still warranted, CPIC recommends considering titrating the TCA to a higher target dose (compared to normal metabolizers) and using therapeutic drug monitoring to guide dose adjustments. For CYP2D6 intermediate metabolizers, CPIC recommends considering a 25% reduction of the starting dose, and for CYP2D6 poor metabolizers, to avoid the use of tricyclics because of the potential for side effects. If a tricyclic is still warranted for CYP2D6 poor metabolizers, CPIC recommends considering a 50% reduction of the starting dose while monitoring drug plasma concentrations to avoid side effects. For CYP2C19 ultrarapid metabolizers, CPIC recommends avoiding the use of tertiary amines (e.g., imipramine) due to the potential for a sub-optimal response, and to consider an alternative drug not metabolized by CYP2C19, such as the secondary amines nortriptyline or desipramine. For CYP2C19 poor metabolizers, CPIC recommends avoiding tertiary amine use due to the potential for sub-optimal response, and to consider an alternative drug not metabolized by CYP2C19. If a tertiary amine is still warranted for CYP2C19 poor metabolizers, CPIC recommends considering a 50% reduction of the starting dose while monitoring drug plasma concentrations to avoid side effects.
Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of major depressive and anxiety disorders, and may be used to treat other psychiatric conditions. Citalopram/escitalopram are metabolized by cytochrome P450 2C19 (CYP2C19) and variations in CYP2C19 may affect drug exposure. Compared to extensive metabolizers, CYP2C19 ultrarapid metabolizers may have significantly lower exposure to citalopram/escitalopram while elevated concentrations of these drugs have been observed in poor metabolizers. Therapeutic guidelines for the SSRIs citalopram/escitalopram based on CYP2C19 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Selective serotonin reuptake inhibitors (SSRIs) are used for the treatment of major depressive and anxiety disorders, and may be used to treat other psychiatric conditions. Sertraline is in part metabolized by cytochrome P450 2C19 (CYP2C19) and variations in CYP2C19 may affect drug exposure. CYP2C19 poor metabolizers might exhibit reduced oral clearance of sertraline and side effects in CYP2C19 poor metabolizers have also been reported to be more frequent than in normal metabolizers. Therapeutic guidelines for the SSRI sertraline based on CYP2C19 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website.
Multiminicore disease is a disorder that primarily affects muscles used for movement (skeletal muscles). This condition causes muscle weakness and related health problems that range from mild to life-threatening.Researchers have identified at least four forms of multiminicore disease, which can be distinguished by their characteristic signs and symptoms. The most common form, called the classic form, causes muscle weakness beginning in infancy or early childhood. This weakness is most noticeable in muscles of the trunk and neck (axial muscles) and is less severe in the arm and leg muscles. Muscle weakness causes affected infants to appear ""floppy"" (hypotonic) and can delay the development of motor skills such as sitting, standing, and walking. The disease causes muscles of the ribcage and spine to stiffen. When combined with weakness of the muscles needed for breathing, this stiffness leads to severe or life-threatening respiratory problems. Almost all children with multiminicore disease develop an abnormal curvature of the spine (scoliosis), which appears during childhood and steadily worsens over time.Other forms of multiminicore disease have different patterns of signs and symptoms. They are less common than the classic form, together accounting for about 25 percent of all cases. The atypical forms of the condition tend to be milder and cause few or no problems with breathing. The moderate form with hand involvement causes muscle weakness and looseness of the joints, particularly in the arms and hands. Another form of multiminicore disease, known as the antenatal form with arthrogryposis, is characterized by stiff, rigid joints throughout the body (arthrogryposis), distinctive facial features, and other birth defects. Paralysis of the eye muscles (external ophthalmoplegia) is a primary feature of another atypical form of multiminicore disease. This form of the condition also causes general muscle weakness and feeding difficulties that appear in the first year of life.Many people with multiminicore disease also have an increased risk of a developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a particular type of muscle relaxant. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly.Multiminicore disease gets its name from small, disorganized areas called minicores, which are found in muscle fibers of many affected individuals. These abnormal regions can only be seen under a microscope. Although the presence of minicores can help doctors diagnose multiminicore disease, it is unclear how they are related to muscle weakness and the other features of this condition.
Complete atrioventricular canal (CAVC), also referred to as complete atrioventricular septal defect, is characterized by an ostium primum atrial septal defect, a common atrioventricular valve and a variable deficiency of the ventricular septum inflow.
Aorto-ventricular tunnel is a congenital, extracardiac channel which connects the ascending aorta above the sinotubular junction to the cavity of the left, or (less commonly) right ventricle.
(20p13) leading to deposition of prion protein amyloid.
Joubert syndrome with Jeune asphyxiating thoracic dystrophy (JATD) is an extremely rare genetic bone disorder characterized by the classic features of Joubert syndrome (i.e. malformation of the brainstem causing ataxia, hypotonia,cognitive impairment, and abnormal eyemovements), associated with the skeletal anomalies found in JATD including short-rib dysplasia and narrow thorax causing respiratory failure, short limbs, and metaphyseal changes.
Congenital protein S deficiency is an inherited coagulation disorder characterized by recurrent venous thrombosis symptoms due to reduced synthesis and/or activity levels of protein S.
Pudendal neuralgia (PN) is a chronic neuropathic pain, aggravated by sitting and for which no organic cause can be found by imaging studies. It is often associated with pelvic dysfunction.
Hypertrichosis-acromegaloid facial appearance syndrome (HAFF) is a very rare multiple congenital abnormality syndrome manifesting from birth with progressive hypertrichosis congenita terminalis (thick scalp hair extending onto the forehead with generalized increased body hair) associated with a typical acromegaloid facial appearance (thick eyebrows, prominent supraorbital ridges, broad nasal bridge, anteverted nares, long and large philtrum, and prominent mouth with full lips) appearing during childhood. HAFF seems to belong to a spectrum of phenotypes with the clinically overlapping acromegaloid facial appearance syndrome and hypertrichotic osteochondrodysplasia, Cantù type (see these terms).
Congenital enterocyte heparan sulphate deficiency is characterised by massive enteric protein loss, secretory diarrhoea, and intolerance to enteral feeds during the first few weeks of life.
This syndrome is characterised by the association of severe congenital colitis with sensorineural deafness.
Aniridia - ptosis - intellectual disability - familial obesity is an extremely rare syndrome described in three members of a family (a mother and her two children) that is characterized by the association of various ocular abnormalities (partial or complete aniridia, ptosis, pendular nystagmus, corneal pannus, , persistent pupillary membrane, lenticular opacities, foveal hypoplasia, and low visual acuity) with various systemic anomalies including intellectual disability and obesity in the two children, and alopecia, cardiac abnormalities, and frequent spontaneous abortion in the mother. There have been no further descriptions in the literature since 1986.
Isolated lissencephaly type 1 without known genetic defects belongs to the genetically heterogeneous group, classic lissencephaly (see this term). It is a diagnosis of exclusion, when neither associated malformations nor family history are present, and in the absence of mutations of genes known to be involved in classic lissencephaly. Clinically patients present with the common features of classic lissencephaly such as developmental delay, intellectual disability, and seizures.
Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both the central and peripheral nervous system (and in some cases other systems and organs), and characterized by degeneration or abnormal development of the cerebellum and spinal cord and, in most cases, early onset occurring before the age of 20 years.
Intractable diarrhea-choanal atresia-eye anomalies syndrome is characterised by the association of intractable diarrhoea of infancy with choanal atresia. Short stature, a prominent and broad nasal bridge, micrognathia, single palmar creases, chronic corneal inflammation, cytopenia, and abnormal hair texture were also reported. So far, the syndrome has been described in three children from the same family. The absence of intellectual deficit and immune deficiency allow this syndrome to be distinguished from other forms of intractable diarrhoea of infancy described previously.
Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome is characterised by ataxia, delayed dentition, hypomyelination and cerebral atrophy. So far, eight cases have been described.
Primary laryngeal lymphangioma is a rare, benign, congenital malformation of the lymphatic system characterized by a polypoidal, variable-sized, soft tissue mass located in the larynx. Most lesions manifest by the 2nd year of life and, depending on the size, patients may present with changes in voice, dysphagia, stridor, airway obstruction and/or respiratory distress. Cystic hygroma of the neck is frequently associated.
This syndrome is characterized by a sensory and autonomic axonal neuropathy, sensorineural hearing loss and persistent global developmental delay.
Digestive duplication cyst of the tongue is an extremely rare otorhinolaryngological malformation which occurs during early embryogenesis and is characterized by a single, and on occasion multiple, cystic lesion that is most frequently located in the anterior portion of the tongue, either deeply embedded within it or superficially on it. Depending mostly on size and location of the cyst, patients could be asymptomatic or could present a wide array of symptoms, such as varying degrees of respiratory and feeding difficulties, lingual swelling and protrusion, dysphagia, and more rarely, recurrent bleeding or brownish discharge from a lingual sinus.
Polyrrhinia is an extremely rare, major congenital malformation characterized by complete duplication of the nose resulting in twofully developed noses often associated with choanal atresia, causing respiratory distress and necessitating surgical repair.
Supernumerary nostril is an extremely rare congenital malformation characterized by the presence of one or more accessory nostrils, with or without accessory cartilage, located medially, above, below or laterally to the other nostrils. Unlike in polyrhinia (see this term) there is no duplication of the nasal septum/cavity. Supernumerary nostril is often associated with other congenital malformations usually of face.
Proboscis lateralis (PL) is a rare congenital facial abnormality characterized by failed development of the external nose on one side that is replaced by a tubular structure composed of skin and soft tissue usually attached at the inner canthus of the eye and therefore often associated with maldevelopment of the nasal cavity or paranasal sinuses of the affected side. PL is also associated with other craniofacial abnormalities such as orbital anomalies, cleft lip/palate, frontal encephalocele and holoprosencephaly (see these terms).
Ring chromosome 20 syndrome is marked by a characteristic seizure phenotype. Depending on the amount of chromosomal loss and associated mosaicism, ring(20) can be associated with macrocephaly, mild to moderate intellectual deficit, or behavioural problems. In rare cases, brain, kidney or heart malformations may be present.
Coloboma of superior eyelid is a rare developmental defect during embryogenesis characterized by a typically unilateral, partial or full-thickness, variably sized defect of the superior eyelid, ranging from a small notch to complete absence of the entire lid, which is commonly triangular in shape (with base at eyelid margin) and located on the medial third of the lid. It can occur isolated, associated with other anomalies (e.g. ocular/orbital and facial), or as part of a syndrome.
Coloboma of inferior eyelid is a rare developmental defect during embryogenesis characterized by a unilateral or bilateral, partial or full-thickness, variably sized defect of the inferior eyelid (ranging from a small notch to complete absence of the entire lid) which is usually triangular in shape (with base at eyelid margin) and located on the lateral third of the lid. It can occur isolated, associated with facial clefting or as part of a syndrome.
Distal monosomy 17q is a very rare chromosomal disorder of unknown prevalence characterized by multiple craniofacial (microcephaly and eye, ear, and nose deformities), limb and other multiple organ abnormalities, growth and motor retardation and intellectual deficit. The syndrome is frequently lethal. The deletions include 17(q21.3q23), 17(q21.3q24.2), 17(q23.q24.3) and 17(q23.1q24.2).
(5q35.1). Various combinations of signs may result from deletions of variable extent depending on the genes comprised in the deleted segment.
Chronic cutaneous lupus erythematosus (CCLE) is a form of cutaneous lupus erythematosus (CLE; see this term) that includes five different forms: discoid lupus erythematosus (DLE), chilblain lupus, hypertrophic or verrucous lupus erythematosus, lupus erythematosus tumidus, and lupus erythematosus panniculitis (see these terms).
X-linked intellectual deficit, Cilliers type is characterized by mild intellectual deficit associated with short stature, hypergonadotropic hypogonadism, microcephaly and mild facial dysmorphism (deep-set eyes, prominent supraorbital ridges, a high nasal bridge and large ears).
X-linked intellectual deficit, Van Esch type is characterized by mild to moderate intellectual deficit associated with low birth weight, short stature, microcephaly and variable hypergonadotropic hypogonadism.
The hereditary dentin disorders, dentinogenesis imperfecta (DGI) and dentin dysplasia (DD), comprise a group of conditions characterized by abnormal dentin structure affecting either the primary or both the primary and secondary dentitions.
Congenital cardiac diverticulum (CCD) is a very rare congenital malformation characterized by a muscular appendix emerging from the left ventricular apex, rarely from the right ventricle or from both chambers, with clinical manifestations ranging from asymptomatic to life-threatening hemodynamic collapse.
Meyer dysplasia of the femoral head is a mild localized form of skeletal dysplasia characterized by delayed, irregular ossification of femoral capital epiphysis.
Intermediate anorectal malformation is a rare, genetic, non-syndromic subtype of anorectal malformation, resulting from a developmental defect during embryogenesis, characterized by a wide spectrum of anorectal anomalies lying between the pubococcygeal line and the ischial tuberosity (e.g., rectovestibular and rectovaginal fistulas in the female, rectobulbar fistula in the male, and anal agenesis). Patients may present with failure to pass meconium, failure to thrive, and recurrent urinary tract infections.
This syndrome is characterized by severe intellectual deficit, kyphosis with onset in childhood and cataract with onset in late adolescence.
Nonrhizomelic chondrodysplasia punctata is a form of chondrodysplasia punctata (see this term), a group of diseases in which the common characteristic is bone calcifications near joints from birth. Nonrhizomelic chondrodysplasia punctata is not an entity in itself but covers several diseases with variable clinical findings and modes of transmission.
Mycosis fungoides (MF) and its variants represent the most common forms of cutaneous T-cell lymphomas. The term MF is restricted to the classical form characterized by the slow progression of patches, plaques and tumors, and to variants with a similar indolent course.
Major hypertriglyceridemia comprises a group of endocrine diseases characterized by permanently high levels of triglycerides (TG) in the blood (higher than 4g/L after 12 hours of fasting) and an increased risk of acute pancreatitis, making screening essential.
Bone dysplasia Azouz type is a form of generalized enchondromatosis with involvement of the spine (so called spondyloenchondromatosis). Spondyloenchondromatosis is a very rare skeletal dysplasia characterized by severe platyspondyly, and mild involvement of hands and feet.
Overlap myositis (OM) is a form of idiopathic inflammatory myopathy (IIM) characterized by myositis with at least one clinical and/or autoantibody overlap feature.
Craniosynostosis, Herrmann-Opitz type is a rare bone development disorder characterized by intellectual disability, short stature, turribrachycephaly, facial dysmorphism (i.e. severe hypertelorism, hypoplasia of supraorbital ridges, abnormal ears, and micrognathia), bony defects of the occiput, and digital anomalies (incl. syndactyly, oligodactyly, and/or brachydactyly). Urethral atresia has also been reported. There have been no further descriptions in the literature since 1987.
Familial isolated arrhythmogenic right ventricular dysplasia (ARVC) is the familial autosomal dominant form of ARVC (see this term), a heart muscle disease characterized by life-threatening ventricular arrhythmias with left bundle branch block configuration that may manifest with palpitations, ventricular tachycardia, syncope and sudden fatal attacks, and that is due to dystrophy and fibro-fatty replacement of the right ventricular myocardium that may lead to right ventricular aneurysms.
Permanent congenital hypothyroidism is a type of congenital hypothyroidism (CH; see this term), a thyroid hormone deficiency present from birth.
Primary congenital hypothyroidism is a type of permanent congenital hypothyroidism (see this term), a permanent thyroid hormone deficiency that is present from birth.
Familial anetoderma is an extremely rare genetic skin disease characterized by loss of elastin tissue leading to localized areas of flaccid skin and a family history of the disorder.
White fibrous papulosis of the neck (WFPN) is a rare, acquired, dermal elastic tissue disorder characterized by multiple, 2-3 mm sized, non-confluent, asymptomatic, white or pale-colored, non-follicular, firm papular lesions occurring predominantly on the lateral or posterior aspects of the neck. Other, rarely reported sites include inferior axillae, central mid-back and upper sternal region.
Pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-PDE) is a rare, acquired, idiopathic dermal tissue disorder characterized by numerous, asymptomatic, 2-3 mm, yellowish, non-follicular papules that tend to converge into cobblestone-like plaques which are distributed symmetrically over the posterior neck, supraclavicular region, axillae, and sometimes abdomen. Unlike PXE, these skin lesions show select elimination (absence or marked loss) of elastic fibers in the papillary dermis and there is no systemic involvement.
Beta-thalassemias associated with hemoglobin (Hb) anomalies result in a variable clinical spectrum, ranging from asymptomatic to severe, depending on the severity of the thalassemia mutation and on the type of the Hb anomaly [hereditary persistence of fetal Hb, delta-beta-thalassemia, Hb C - beta-thalassemia, Hb E - beta-thalassemia and Hb S - beta-thalassemia (see these terms)].
Primary unilateral adrenal hyperplasia (PUAH) is a surgically-correctable form of primary (hyper) aldosteronism (PA; see this term) characterized by renin suppression, unilateral aldosterone hypersecretion, and moderate to severe hypertension secondary to hyperplasia of the adrenal gland.
Adrenocortical carcinoma with pure aldosterone hypersecretion (pure APAC) is a very rare surgically-correctable form of primary aldosteronism (PA; see this term) due to an aldosterone-secreting adrenal malignancy.
Surgically correctable forms of primary aldosteronism (also known as primary hyperaldosteronism; see this term) are characterized by unilateral aldosterone hypersecretion and renin suppression, associated with varying degrees of hypertension and hypokalemia.
Epibulbar lipodermoid ? preauricular appendages ? polythelia is a branchial arch syndrome described in seven sibs of one Danish family and characterized by supernumerary nipples (polythelia), preauricular appendages and often binocular epibulbar lipodermoids or unilateral subconjunctival lipodermoids.
PSP-Pure akinesia with gait freezing (PSP-PAGF) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease.
PSP-progressive non fluent aphasia (PSP-PNFA) is an atypical variant of progressive supranuclear palsy (PSP; see this term), a rare late-onset neurodegenerative disease. Unlike classic PSP (Richardson syndrome) patients present with an isolated speech production problem years before developing other motor features of PSP.
Central bilateral macrogyria is a neuronal migration disorder characterised by pseudobulbar palsy, developmental delay, mild mental retardation and epilepsy. It has been described in at least four children.
Sporadic adult-onset ataxia of unknown etiology describes a group of non-hereditary degenerative ataxias characterized by a slowly progressive cerebellar syndrome (with ataxia of stance and gait, upper limb dysmetria and intention tremor, ataxic speech, and oculomotor abnormalities), presenting in adulthood (at around 50 years of age), that is not due to a known cause. Extracerebellar symptoms (e.g., decreased vibration sense and absent or decreased ankle reflexes), polyneuropathy and mild autonomic dysfunction may also be present. Mild cognitive impairment has also rarely been reported.
Superficial siderosis is a rare neurologic disease characterized by progressive sensorineural hearing loss, cerebellar ataxia, pyramidal signs, and neuroimaging findings revealing hemosiderin deposits in the spinal and cranial leptomeninges and subpial layer. The disease progresses slowly and patients may present with mild cognitive impairment, nystagmus, dysmetria, spasticity, dysdiadochokinesia, dysarthria, hyperreflexia, and Babinski signs. Additional features reported include dementia, urinary incontinence, anosmia, ageusia, and anisocoria.
Spondylometaphyseal dysplasias are a heterogeneous group of disorders associated with walking and growth disturbances that become evident during the second year of life.
Pure mitochondrial myopathy is a rare mitochondrial disease characterized by exclusive skeletal muscle involvement, without clinical evidence of other organ involvement, manifesting with progressive limb weakness, proximal limb muscle atrophy, and eye muscle anomalies (e.g. ocular motility restriction, ptosis). Patients may present with lactic acidosis, diffuse myalgia and overall fatigability (particularly during/after physical activities), dysphagia, and diminished deep tendon reflexes.
Ring chromosome Y is a rare chromosome Y structural anomaly, with a highly variable phenotype, mostly characterized by short stature, partial to total gonadal failure, sexual infantilism, genital anomalies (e.g. ambiguous genitalia, hypospadias, cryptorchidism), and azoospermia or oligozoospermia. Additional reported features include speech delay, obesity, and acanthosis nigricans. Gender dysphoria and comorbid bipolar disorder have also been observed.
Mycophenolate mofetil (MMF) embryopathy is a malformative syndrome due to the teratogenic effect of MMF, an effective immunosuppressive agent widely used for the prevention of organ rejection after organ transplantation.
Bifid nose is a rare congenital malformation of presumed autosomal dominant or recessive inheritance characterized by clefting of the nose ranging from a minimally noticeable groove in the columella to complete clefting of the underlying bones and cartilage (resulting in two half noses) with a usually adequate airway. Bifid nose may be seen in frontonasal dysplasia while other malformations such as hypertelorbitism and midline clefts of the lip may also be associated.
Omodysplasia is a rare skeletal dysplasia characterized by severe limb shortening and facial dysmorphism. Two types of omodysplasia have been described: an autosomal recessive or generalized form (also referred to as micromelic dysplasia with dislocation of radius) marked by severe micromelic dwarfism with predominantly rhizomelic shortening of both the upper and lower limbs, and an autosomal dominant form in which stature is normal and shortening is limited to the upper limbs.
Bile acid CoA ligase deficiency and defective amidation is an anomaly of bile acid synthesis (see this term) characterized by fat malabsorption, neonatal cholestasis and growth failure.
Pericardial and diaphragmatic defect is a rare combination of absent pericardium with congenital diaphragmatic defect.
Congenital viral infections with enteroviruses (EV) including coxsackie viruses and ECHO viruses is an infectious embryofetopathy that have been reported to cause spontaneous abortion, stillbirth, fetal malformations and acute systemic illness in the newborn.
Methylmalonic acidemia is an inborn error of vitamin B12 metabolism characterized by gastrointestinal and neurometabolic manifestations resulting from decreased function of the mitochondrial enzyme methylmalonyl-CoA mutase.
Ketamine-induced biliary dilatation is an acquired biliary tract disease caused by the abusive consumption of ketamine, which results in the fusiform dilatation of the common bile ducts (CBD) without obstructive lesions or dilatation of the intrahepatic biliary ducts. Possible manifestations of the underlying cholangiopathy include epigastric pain and impaired liver function. Severity of CBD dilatation appears to correlate with the duration of ketamine consumption and the condition has been reported to be reversible in abstinent patients.
Split hand is a rare, non-syndromic limb reduction defect, clinically and genetically heterogeneous, characterized by bilateral or unilateral underdevelopment or absence of the central rays of the autopod, with absence of all or just some of the central phalanges and at least part of the associated metacarpal bones, yielding a cleft appearance of the hand. It is frequently associated with syndactyly and aplasia/hypoplasia of remaining digits and metacarpal bones. No other dysmorphic features are observed and development is appropriate for age.
Hyperphalangy is a congenital, non-syndromic limb malformation characterized by the presence of an accessory phalanx between metacarpal/metatarsal and proximal phalanx, or between any two other phalanges of a digit, excluding the thumb. Hypherphalangy is almost always bilateral and patients present no more than five digits and no other skeletal anomalies.
Split hand, unilateral is a rare, non-syndromic limb reduction defect, clinically and genetically heterogeneous, characterized by unilateral underdevelopment or absence of the central rays of the autopod, with absence of all, or just some, of the central phalanges and at least part of the associated metacarpal bones, yielding a cleft appearance of the hand. It is frequently associated with syndactyly and aplasia/hypoplasia of remaining digits and metacarpal bones. No other dysmorphic features are observed and development is appropriate for age.
Split hand, bilateral is a rare, non-syndromic limb reduction defect, clinically and genetically heterogeneous, characterized by bilateral underdevelopment or absence of the central rays of the autopod, with absence of all, or just some, of the central phalanges and at least part of the associated metacarpal bones, yielding a cleft appearance of the hand. It is frequently associated with syndactyly and aplasia/hypoplasia of remaining digits and metacarpal bones. No other dysmorphic features are observed and development is appropriate for age.
Familial primary hypomagnesemia with normocalcuria (FPHN) is a form of familial primary hypomagnesemia (FPH; see this term) which is characterized by low magnesium values but normal calcium values in the serum. The disorder consists of three distinct forms which are: autosomal recessive primary hypomagnesemia with normocalcuria and hypocalcemia (ARPHN), familial primary hypomagnesemia with normocalcuria and normocalcemia (FPHNN) and isolated autosomal dominant hypomagnesemia, Glaudemans type (see these terms).
Paraquat poisoning is a rare intoxication with paraquat (a non-selective bipyridilium herbicide that has been banned in Europe), usually occurring through ingestion of the poison, and that presents with caustic injury of the oral cavity and pharynx, as well as nausea, vomiting, epigastric pain, lethargy, loss of consciousness and fever. Patients may develop potentially life-threatening complications such as hepatic dysfunction, acute tubular necrosis and renal insufficiency, and respiratory failure (due to pulmonary fibrosis) due to its inherent toxicity and lack of effective treatment. Intoxication via inhalation, injection and dermal or mucus contact have also been reported.
Congenital pulmonary vein (PV) stenosis or atresia is a rare progressive life-threatening great vessels anomaly characterized by narrowing and obstruction of one or more normally positioned PV at their junction with the left atrium, that usually presents during early infancy with dyspnea, tachypnea, and repeated pulmonary infections, and eventually, when all PV of one lung are affected, results in pulmonary hypertension (PH) and consecutive pulmonary arterial hypertension (PAH) (see this term). It may manifest as an isolated lesion or associated with other cardiac defects such as congenital pulmonary venous return anomaly (see this term) and septal defects.
Familial nonmedullary thyroid carcinoma (fNMTC) is a rare non-syndromic form of thyroid cancer characterized by occurrence of thyroid carcinoma (TC) as the primary feature in a familial setting.
Congenital achiasma is a rare, genetic, non-syndromic cranial nerve and nuclear aplasia malformation characterized by the congenital absence of the optic chiasm, resulting from the failure of the optic nerve fibers to cross over and decussate to the contralateral hemisphere, leading to decreased vision, strabismus and congenital nystagmus in infancy.
. Resolution of photosensitivity is reported in up to 50% of individuals after 15 years or more, with contact allergies persisting.
Arbovirosis are polymorphic diseases caused by arboviruses and are classically characterized by encephalitis and hemorrhage, however, most commonly only aspecific fever is observed.
Familial primary hypomagnesemia (FPH) is a rare mineral absorption and transport disorder characterized by a selective defect in renal or intestinal magnesium (Mg) absorption, resulting in a low Mg concentration in the blood.
Folliculitis decalvans is a rare chronic inflammatory cicatricial alopecia of the scalp occurring in middle-aged adults and characterized by the development of alopecic patches with slowly centrifugal spread predominantly in the vertex and occipital area of the scalp, associated with perifollicular erythema, follicular pustules and hemorrhagic crusts.
Serine-deficiency syndrome is a very rare infantile-onset potentially treatable neurometabolic disorder characterized clinically by microcephaly, neurodevelopmental disorders and seizures. Three serine-deficiency syndromes have been described: 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, 3-phosphoserine phosphatase (3-PSP) deficiency, and phosphoserine aminotransferase deficiency (see these terms).
Acute opioid poisoning is a rare intoxication with opioids, a large group of alkaloid analgesics, mainly characterized by miosis (pinpoint pupil), respiratory depression (bradypnea/apnea) and central nervous system depression (sedation or coma). Other manifestations include hypotension, reduced bowel motility, hypothermia and hypoglycemia. Naloxone, a competitive inhibitor of the mu-opioid receptor, is a potent antagonist and is used as the antidote for opioid intoxication.
Hereditary glaucoma is a clinically diverse group of rare eye disorders with genetic predisposition characterized by elevated intraocular pressure (IOP) and glaucomatous changes of the optic nerve head, leading to field defects, visual loss and blindness. Hereditary glaucoma can be sub-classified as primary (congenital glaucoma, juvenile glaucoma) or secondary according to the presence or absence of systemic or other ocular anomalies (iridogoniodysgenesis, Stickler syndrome, Coats syndrome; see these terms). The clinical presentation is variable and is based on age, severity of glaucoma, presence of ocular abnormalities and development of secondary IOP related abnormalities.
Acute tricyclic antidepressant (TCA) poisoning is a potentially lethal intoxication that is characterized by life-threatening arrhythmias (sinus tachycardias, premature ventricular contractions, ventricular arrhythmias), anticholinergic toxidrome (mydriasis, dry mucous membrane, tachycardia, hypertension), central nervous system toxicity (lethargy, coma, myoclonic jerks), refractory hypotension, and sudden death.
Acute poisoning with a membrane-stabilizing effect is potentially life-threatening. The principle drugs involved are tricyclic antidepressants, chloroquine, some types of beta blockers, class IA antiarrhythmics, carbamazepin and cocaine.
Pemphigus is a group of chronic autoimmune skin diseases characterised by blister formations on the outer layer of the skin and the mucous membranes. Three clinical forms have been characterised, one of which is superficial pemphigus, including the seborrheic, erythematosus, foliaceous and herpetiform variants.
Multiple familial keratoacanthoma (KA) of Witten and Zak is a rare a rare inherited skin cancer syndrome and is characterized by the coexistence of features characteristic of both multiple KA, Ferguson Smith type and generalized eruptive keratoacanthoma (see these terms), such as multiple small miliary-type lesions, larger self-healing lesions, and nodulo-ulcerative lesions .Lesions do not have a predilection for the mucosal surfaces. Transmission is autosomal dominant.
Anorectal malformations (ARM) comprise a wide spectrum of malformations involving the distal anus and rectum as well as the urinary and genital tracts, which can affect boys and girls.
Peripartum cardiomyopathy (PPCM) is an idiopathic, potentially fatal form of dilated cardiomyopathy that develops during the final month of pregnancy or within five months after delivery.
Angioedema is characterized by the occurrence of transitory and recurrent subcutaneous and/or submucosal edemas resulting in swelling and/or abdominal pain.
Segmental odontomaxillary dysplasia (SOD) is a rare disorder characterized by unilateral enlargement of the right or left maxillary alveolar bone and gingiva in the region from the back of the canines to the maxillary tuberosity. In the enlarged region, dental abnormalities such as missing teeth, abnormal spacing and delayed eruption occur.
Immunodeficiency due to selective anti-polysaccharide antibody deficiency is characterized by normal immunoglobulin levels (including IgG sub-classes) but impaired polysaccharide responsiveness (IPR).
Idiopathic acute eosinophilic pneumonia (IAEP) is an eosinophilic pneumonia of undetermined etiology that is characterized by acute febrile hypoxic respiratory failure associated with diffuse radiographic infiltrates and pulmonary eosinophilia, but without concurring allergy or infection.
This syndrome is characterised by the association of global developmental delay, osteopenia and skin anomalies.
Ossification anomalies-psychomotor developmental delay syndrome is characterised by hypomineralisation of the cranial bones, thoracic dystrophy, hypotonia, and abnormal and slender long bones due to an alteration in remodelling during ossification.
Primary lymphedema is a lymphatic system malformation characterized by swelling of an extremity that can be associated with other lymphatic effusions, due to an underlying developmental anomaly of the lymphatic system (abnormal lymphoangiogenesis). It can be hereditary or not and be congenital or late onset.
Localised lipodystrophies are characterised by loss of subcutaneous tissue from small regions of the body.
Creatine deficiency syndrome (CDS) comprises a group of inborn errors of creatine metabolism, characterized by a global developmental delay, intellectual disability and associated neurological (seizures, movement disorders, myopathy) and behavioral manifestions. CDS includes two creatine biosynthesis disorders; guanidinoacetate methyltransferase deficiency and L- Arginine: glycine amidinotransferase deficiency, as well as X-linked creatine transporter deficiency.
gene, known to be involved in oral-facial-digital syndrome.
Craniofacial conodysplasia is characterised by craniofacial dysplasia, cone-shaped physes of the hands and feet, and neurological manifestations resembling cerebral palsy. It has been described in one family. The syndrome appeared to be transmitted as a dominant trait.
X-linked intellectual disability-precocious puberty-obesity syndrome is characterised by moderate intellectual deficit and precocious puberty. It has been described in three males from two generations of one Australian family. Morbid obesity was noted in the mothers of the patients. Transmission is X-linked.
X-linked intellectual disability-acromegaly-hyperactivity syndrome is characterised by severe intellectual deficit, acromegaly and hyperactivity. The syndrome has been described in two half-brothers. Dysarthria, aggressive behaviour, a characteristic facies (an acromegalic and triangular face with a long nose) and macroorchidism were also present. The mother displayed moderate intellectual deficit and milder facial anomalies. Central nervous system anomalies were identified in the two boys: subarachnoid cysts and hyperdensity in the pontine region.
X-linked intellectual disability-ataxia-apraxia syndrome is characterised by ataxia, apraxia, intellectual deficit and/or seizures. It has been described in nine males in two unrelated Danish families. It is transmitted as an X-linked recessive syndrome with partial clinical expression in obligate female carriers.
Lissencephaly type 3-familial fetal akinesia sequence syndrome is characterised by the association of microencephaly, agenesis of the corpus callosum, brainstem hypoplasia, cystic cerebellum and foetal akinesia sequence. Less than 10 cases have been described so far. The syndrome is transmitted as an autosomal recessive trait and may be an allelic variant of Neu-Laxova syndrome and lissencephaly type III with metacarpal bone dysplasia (see these terms).
Obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome is characterised by precocious obesity, congenital hypothyroidism, neonatal colitis, cardiac hypertrophy, craniosynostosis and developmental delay. It has been described in two brothers, one of whom died within the first month of life. The parents of the two children were nonconsanguineous and in good health, however, the pregnancies were complicated by a maternal HELLP syndrome (Haemolysis, Elevated Liver enzymes and Low Platelets). The mode of inheritance has not yet been clearly established.
Immunotactoid or fibrillary glomerulopathy is a group of very rare glomerular diseases, composed of immunotactoid glomerulopathy (ITG) and non-amyloid fibrillary glomerulopathy (non-amyloid FGP) (see these terms), that are characterized by mesangial deposition of monoclonal microtubular or polyclonal fibrillar deposits. Both present clinically with nephrotic range proteinuria, hematuria and renal insufficiency leading to renal failure in many cases. ITG is more likely to manifest with underlying lymphoproliferative disease, hypocomplementemia, dysproteinemia, monoclonal gammopathy or occult cryoglobulinemia. Non-amyloid FGP is 10 times more frequent than ITG.
Congenital alacrima is characterised by deficient lacrimation (ranging from a complete absence of tears to hyposecretion of tears) that is present from birth.
Congenital ectropion uveae is a rare, genetic, non-syndromic developmental defect of the eye characterized by the presence of iris pigment epithelium on the anterior surface of the iris, anterior insertion of the iris, angle dysgenesis and progressive open-angle glaucoma (the latter may present in infancy or may develop later in life). Patients may manifest with headaches, ocular pain, photophobia, and redness, watering and/or swelling of the eye. It can often be associated with neurofibromatosis and less commonly with other ocular abnormalities.
Juvenile idiopathic arthritis (JIA) is the term used to describe a group of inflammatory articular disorders of unknown cause that begin before the age of 16 and last over 6 weeks. The term juvenile idiopathic arthritis was chosen to signify the absence of any known mechanism underlying the disorder and to highlight the necessity of excluding other types of arthritis occurring in well defined diseases (in particular arthritis occurring in association with infectious, inflammatory and haematooncologic diseases).
Congenital megacalycosis is a rare renal malformation, characterized by non-obstructive dilation of the renal calyces as well as an increased calyceal number (12-20), with a normal renal pelvis, ureter, and bladder. It may be unilateral or bilateral and is usually asymptomatic unless complicated by nephrolithiasis and urinary tract infection.
Posterior urethral valve (PUV) is the most common anomaly of fetal lower urinary tract obstruction (LUTO)and is characterized by an abnormal congenital obstructing membrane that is located within the posterior urethra associated with significant obstruction of the male bladder restricting normal bladder emptying.
Epispadias is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex (EEC; see this term) and is characterized in males by an ectopic meatus or a mucosal strip in place of the urethra on the penile dorsum and in females by bifid clitoris and a variable cleft of the urethra.
holoprosencephaly or gyration anomalies). Skull base and facial bones are normal.
Chronic hepatic porphyrias represent a sub-group of porphyrias (see this term). They are characterized by bullous photodermatitis caused by a deficiency of uroporphyrinogen decarboxylase (URO-D; the fifth enzyme in the heme biosynthesis pathway). Chronic hepatic porphyria encompasses two diseases: porphyria cutanea tarda and hepatoerythropoietic porphyria (extremely rare) (see these terms).
Thyroid dysgenesis is a type of primary congenital hypothyroidism (see this term), a permanent thyroid hormone deficiency that is present from birth.
Primary congenital hypothyroidism without thyroid developmental anomaly is a type of primary congenital hypothyroidism (see this term) in which the thyroid gland is anatomically normal.
Congenital hypothyroidism due to transplacental passage of maternal thyroid-stimulating hormone (TSH)-binding inhibitory antibodies is a type of transient congenital hypothyroidism (see this term), a thyroid hormone deficiency that is not permanent.
Idiopathic congenital hypothyroidism is a type of primary congenital hypothyroidism (see this term) whose cause and prevalence are unknown.
Non-amyloid fibrillary glomerulopathy (non-amyloid FGP) is a rare cause of glomerulonephritis (GN) characterized by glomerular accumulation of non-amyloid fibrils in the mesangium and the glomerular (and rarely tubular) basement membrane, that mainly presents with renal insufficiency, micro-hematuria and nephrotic range proteinuria. Non-amyloid FGP and immunotactoid glomerulopathy (ITG, see this term) are often grouped together as pathogenetically related diseases.
Immunotactoid glomerulopathy (ITG) is a very rare condition characterized by glomerular accumulation of microtubules in the mesangium and the glomerular basement membrane, that mainly presents with proteinuria, micro-hematuria, nephrotic syndrome, renal insufficiency and hematologic malignancy. ITG and non-amyloid fibrillary glomerulopathy (non-amyloid FGP, see this term) are often grouped together as pathogenetically related diseases.
Nonsyndromic pontocerebellar hypoplasias (PCH) are a rare heterogeneous group of diseases characterized by hypoplasia and atrophy and/or early neurodegeneration of the cerebellum and pons. Eight subtypes named type 1-8 have been described (see these terms), generally inherited in an autosomal recessive pattern.
Posterior corneal dystrophies refers to a group of rare genetically determined corneal dystrophies (CDs) characterized by lesions affecting the corneal endothelium and Descemet membrane, and variable effects on vision depending on the type of dystrophy.
Blake pouch cyst is a non-syndromic, usually benign, cystic malformation of the posterior fossa characterized by a midline outpouching of the superior medullary velum into the cisterna magna that results from failure of the rudimental fourth ventricular tela choroidea to regress during embryogenesis. Patients can be asymptomatic or present in childhood or adulthood with clinical manifestations of hydrocephalus, such as headache, hypotonia, vertigo, syncope, vomiting, blurred or double vision, nystagmus, papilledema, and delayed gait development.
Autosomal dominant cerebellar ataxia (ADCA) describes a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by a slowly progressive ataxia of gait, stance and limbs, dysarthria and/or oculomotor disorder, due to cerebellar degeneration in the absence of coexisting diseases. The degenerative process can be limited to the cerebellum (ADCA type 3) or may additionally involve the retina (ADCA type 2), optic nerve, ponto-medullary systems, basal ganglia, cerebral cortex, spinal tracts or peripheral nerves (ADCA type 1) (see these terms). In ACDA type 4 (see this term), a cerebellar syndrome is associated with epilepsy.
Congenital eyelid retraction is a very rare kinetic eyelid anomaly that can affect the upper or lower eyelid, presents at birth, that in some cases can result in corneal exposure, and that may be associated with accessory levator muscle slips.
Complex cortical dysplasia with other brain malformations (CDCBM) is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved (summary by Poirier et al., 2010). Mutation in the TUBB3 gene can also cause congenital fibrosis of extraocular muscles-3A (CFEOM3A; 600638), a milder and somewhat different neurologic phenotype. Genetic Heterogeneity of Complex Cortical Dysplasia With Other Brain Malformations See also CDCBM2 (615282), caused by mutation in the KIF5C gene (604593) on chromosome 2q23; CDCBM3 (615411), caused by mutation in the KIF2A gene (602591) on chromosome 5q12; CDCBM4 (615412), caused by mutation in the TUBG1 gene (191135) on chromosome 17q21; CDCBM5 (615763), caused by mutation in the TUBB2A gene (615101) on chromosome 6p25; and CDCBM6 (615771), caused by mutation in the TUBB gene (191130) on chromosome 6p21 [OMIM]
Congenital myasthenic syndrome is a group of conditions characterized by muscle weakness (myasthenia) that worsens with physical exertion. The muscle weakness typically begins in early childhood but can also appear in adolescence or adulthood. Facial muscles, including muscles that control the eyelids, muscles that move the eyes, and muscles used for chewing and swallowing, are most commonly affected. However, any of the muscles used for movement (skeletal muscles) can be affected in this condition. Due to muscle weakness, affected infants may have feeding difficulties. Development of motor skills such as crawling or walking may be delayed. The severity of the myasthenia varies greatly, with some people experiencing minor weakness and others having such severe weakness that they are unable to walk.Some individuals have episodes of breathing problems that may be triggered by fevers or infection. Severely affected individuals may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis).
Lissencephaly with cerebellar hypoplasia type A (LCHa) is a form of lissencephaly with cerebellar hypoplasia that encompasses classical lissencephaly with thickened cortical gray matter with either no discernable gradient, a gradient with posterior predominance, or a gradient with anterior predominance, and cerebellar vermis hypoplasia.
Lissencephaly with cerebellar hypoplasia type B (LCHb) is a form of lissencephaly with cerebellar hypoplasia characterized by subtle microcephaly, hypotonia and neurological and cognitive development delay. Hippocampal malformation is a characteristic imaging feature of LCHb.
Lissencephaly with cerebellar hypoplasia type C (LCHc) is a severe form of lissencephaly with cerebellar hypoplasia characterized by severe microcephaly, cleft palate, and severe cerebellar and brainstem hypoplasia leading to neonatal death.
Lissencephaly with cerebellar hypoplasia type D (LCHd) is a form of lissencephaly with cerebellar hypoplasia characterized by pronounced microcephaly (at least ± 3 SD), intellectual disability, spastic diplegia and moderate to severe cerebellar hypoplasia involving both vermis and hemispheres.
Lissencephaly with cerebellar hypoplasia type E (LCHe) is a form of lissencephaly with cerebellar hypoplasia, characterized by an abrupt transition from agyria to gyral simplification, near the boundary between frontal and parietal cortex, microcephaly (± 3 SD) and brainstem hypoplasia.
Lissencephaly with cerebellar hypoplasia type F (LCHf) is a severe form of lissencephaly with cerebellar hypoplasia, characterized by a microcephaly of at least - 3 SD and a thick cortex associated with complete absence of the corpus callosum.
Underterminate colitis designates a rare inflammatory bowel disease that clinically resembles Crohn?s disease and ulcerative colitis (see these terms) but that cannot be diagnosed as one of them after examination of an intestinal resection specimen.
Primary cutaneous aggressive epidermotropic CD8+ T-cell lymphoma is a rare form of primary cutaneous T-cell lymphoma characterized by rapidly progressing, localized or disseminated nodules, tumors or eczematous skin lesions. It has a particularly aggressive clinical course with a high tendency to spread, in advanced stages, to extracutaneous locations (the central nervous system, lung, testes). Lymph nodes are often spared.
Neuroacanthocytosis (NA) syndromes are a group of genetic diseases characterized by the association of red blood cell acanthocytosis (deformed erythrocytes with spike-like protrusions) and progressive degeneration of the basal ganglia.
Pulmonary arterial hypertension (PAH, see this entry) associated with HIV infection (PAH-HIV) is a form of PAH characterized by elevated pulmonary arterial resistance leading to right heart failure observed as a complication of HIV infection.
Pulmonary arterial hypertension associated with schistosomiasis (PAHS) is a form of pulmonary arterial hypertension (see this term) characterized by an elevated pulmonary arterial resistance leading to right heart failure, observed as a complication of a chronic schistosomiasis (see this term).
Pulmonary arterial hypertension associated with chronic hemolytic anemia (PAH-CHA) is a form of PAH (see this term) characterized by an elevated pulmonary arterial resistance leading to right heart failure observed as a complication of chronic hemolytic anemia.
Diazoxide-resistant hyperinsulism (DRH) is form of congenital isolated hyperinsulism (see this term) caused by an abnormal insulin production by b-cells in the pancreas that can be diffuse or focal and is characterized by an excessive/ uncontrolled insulin secretion (inappropriate for the level of glycemia), recurrent episodes of profound hypoglycemia and resistance to medical management with diazoxide.
Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly is a rare form of diffuse large B-cell lymphoma occurring most commonly in patients over the age of 50 (usually between 70-75 years of age), without overt immunodeficiency, and presenting with nodal and extranodal involvement (in sites such as the stomach, lung, skin and pancreas) and B symptoms (fever, night sweats, weight loss). The tumor is characterized by an aggressive course and a short survival rate.
Splenic diffuse red pulp small B-cell lymphoma is a rare, indolent B-cell non-Hodgkin lymphoma characterized by abnormal proliferation of small, monomorphous, basophilic B-lymphocytes, with villous cytoplasm, in the splenic red pulp, bone marrow and peripheral blood. It typically presents in the late clinical stages with splenomegaly and moderate lymphocytosis. Cytopenias are rare and likely associated with hypersplenism.
T-B+ severe combined immunodeficiency (SCID; see this term) is a group of rare monogenic primary immunodeficiency disorders characterized by a lack of functional peripheral T lymphocytes with presence of B lymphocytes, resulting in early-onset severe respiratory viral, bacterial or fungal infections, diarrhea and failure to thrive.
T-B- severe combined immunodeficiency (SCID; see this term) is a group of rare monogenic primary immunodeficiency disorders characterized by a lack of functional peripheral T and B lymphocytes, resulting in recurrent early-onset severe respiratory viral, bacterial or fungal infections, diarrhea and failure to thrive. Hypersensitivity to ionizing radiation is a characteristic feature of some of its sub-types.
Localized lichen myxedematosus is a group of skin diseases characterized by the development of papules, nodules and/or plaques with mucin deposits and a variable degree of fibrosis in the absence of thyroid disease. The group comprises five sub-forms: nodular lichen myxedematosus, discrete papular lichen myxedematosus, papular mucinosis of infancy, acral persistent papular mucinosis and self-healing papular mucinosis.
-3 SD). LCH is characterized by cerebellar underdevelopment ranging from vermian hypoplasia to total aplasia with classical or cobblestone lissencephaly. The phenotypic features of LCH include small head circumference (between -2 and -3 standard deviations (SD) forage) at birth and postnatally, moderate to severe intellectual disability, hypotonia and spasticity. Seizures are often observed and infantile spasms have been reported in some rare cases. LCH has been classified into six subgroups according to neuroradiographic properties and are classified LCH type A to F.
Self-healing papular mucinosis is a rare form of localized lichen myxedematosus (see this term) occurring primarily in children and characterized by the development of mucinous papules on various parts of the body (face, neck, trunk, and limbs) that resolve spontaneously within some weeks to months. Systemic symptoms can be observed such as fever, arthralgias and weakness.
Paternal uniparental disomy of chromosome 20 is a very rare chromosomal anomaly in which both copies of chromosome 20 are inherited from the father. The main features described are high birth weight and/or early-onset obesity, relative macrocephaly, and tall stature. Most patients were ascertained during sporadic pseudohypoparathyroidism type 1b (see this term) testing and have UPD involving variable segments of the long arm of chromosome 20.
Cheirospondyloenchondromatosis is an extremely rare type of enchondromatosis of very early onset (from neonatal period to infancy) characterized by symmetrical multiple enchondromas with metacarpal and phalangeal involvement resulting in short hands and feet, platyspondyly, mild to moderate short stature and intellectual disability.
Occupational allergic alveolitis designates a hypersensitivity pneumonitis (see this term) resulting from the inhalation of an antigen to which an individual has been previously sensitized in his/her occupational environment. Symptoms vary depending on the antigen and the form (acute, subacute, chronic) of the disease. They may be cough, dyspnea, chills, fever, weight loss, loss of appetite and general malaise
Feingold syndrome is a disorder that affects many parts of the body. There are two types of Feingold syndrome, distinguished by their genetic cause; both types have similar features that can vary among affected individuals.Individuals with Feingold syndrome type 1 or type 2 have characteristic abnormalities of their fingers and toes. Almost all people with this condition have a specific hand abnormality called brachymesophalangy, which refers to shortening of the second and fifth fingers. Other common abnormalities include fifth fingers that curve inward (clinodactyly), underdeveloped thumbs (thumb hypoplasia), and fusion (syndactyly) of the second and third toes or the fourth and fifth toes.Additional common features of both types of Feingold syndrome include an unusually small head size (microcephaly), a small jaw (micrognathia), a narrow opening of the eyelids (short palpebral fissures), and mild to moderate learning disabilities. Less often, affected individuals have hearing loss, short stature, or kidney or heart abnormalities.People with Feingold syndrome type 1 are frequently born with a blockage in part of their digestive system called gastrointestinal atresia. In most cases, the blockage occurs in the esophagus (esophageal atresia) or in part of the small intestine (duodenal atresia). Individuals with type 2 do not have gastrointestinal atresias.
Leigh syndrome is a severe neurological disorder that usually becomes apparent in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly.The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia), which disrupts eating. These problems often result in an inability to grow and gain weight at the expected rate (failure to thrive). Severe muscle and movement problems are common in Leigh syndrome. Affected individuals may develop weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia). Loss of sensation and weakness in the limbs (peripheral neuropathy), common in people with Leigh syndrome, may also make movement difficult.Several other features may occur in people with Leigh syndrome. Many individuals with this condition develop weakness or paralysis of the muscles that move the eyes (ophthalmoparesis); rapid, involuntary eye movements (nystagmus); or degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). Severe breathing problems are common, and these problems can worsen until they cause acute respiratory failure. Some affected individuals develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. In addition, a substance called lactate can build up in the body, and excessive amounts are often found in the blood, urine, or the fluid that surrounds and protects the brain and spinal cord (cerebrospinal fluid) of people with Leigh syndrome.The signs and symptoms of Leigh syndrome are caused in part by patches of damaged tissue (lesions) that develop in the brains of people with this condition. A medical procedure called magnetic resonance imaging (MRI) reveals characteristic lesions in certain regions of the brain. These regions include the basal ganglia, which help control movement; the cerebellum, which controls the ability to balance and coordinates movement; and the brainstem, which connects the brain to the spinal cord and controls functions such as swallowing and breathing. The brain lesions are often accompanied by loss of the myelin coating around nerves (demyelination), which reduces the ability of the nerves to activate muscles used for movement or relay sensory information from the rest of the body back to the brain.
Benign familial neonatal seizures (BFNS) is a condition characterized by recurrent seizures in newborn babies. The seizures begin around day 3 of life and usually go away within 1 to 4 months. The seizures can involve only one side of the brain (focal seizures) or both sides (generalized seizures). Many infants with this condition have generalized tonic-clonic seizures (also known as grand mal seizures). This type of seizure involves both sides of the brain and affects the entire body, causing muscle rigidity, convulsions, and loss of consciousness.A test called an electroencephalogram (EEG) is used to measure the electrical activity of the brain. Abnormalities on an EEG test, measured during no seizure activity, can indicate a risk for seizures. However, infants with BFNS usually have normal EEG readings. In some affected individuals, the EEG shows a specific abnormality called the theta pointu alternant pattern. By age 2, most affected individuals who had EEG abnormalities have a normal EEG reading.Typically, seizures are the only symptom of BFNS, and most people with this condition develop normally. However, some affected individuals develop intellectual disability that becomes noticeable in early childhood. A small percentage of people with BFNS also have a condition called myokymia, which is an involuntary rippling movement of the muscles. In addition, in about 15 percent of people with BFNS, recurrent seizures (epilepsy) will come back later in life after the seizures associated with BFNS have gone away. The age that epilepsy begins is variable.
Vitelliform macular dystrophy is a genetic eye disorder that can cause progressive vision loss. This disorder affects the retina, the specialized light-sensitive tissue that lines the back of the eye. Specifically, vitelliform macular dystrophy disrupts cells in a small area near the center of the retina called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces.Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the macula. Over time, the abnormal accumulation of this substance can damage cells that are critical for clear central vision. As a result, people with this disorder often lose their central vision, and their eyesight may become blurry or distorted. Vitelliform macular dystrophy typically does not affect side (peripheral) vision or the ability to see at night.Researchers have described two forms of vitelliform macular dystrophy with similar features. The early-onset form (known as Best disease) usually appears in childhood; the onset of symptoms and the severity of vision loss vary widely. The adult-onset form begins later, usually in mid-adulthood, and tends to cause vision loss that worsens slowly over time. The two forms of vitelliform macular dystrophy each have characteristic changes in the macula that can be detected during an eye examination.
Univentricular heart (UVH) is a severe congenital cardiac malformation characterized by both atria related entirely or almost entirely to one functionally single ventricular chamber. The clinical manifestations include congestive heart failure, failure to thrive, cyanosis, hypoxemia and neurodevelopmental disabilities.
Nodular lichen myxedematosus is a rare form of localized lichen myxedematosus (see this term) characterized by the development of skin-coloured mucinous nodules on the limbs and trunk, with mild or absent papular eruption.
Discrete papular lichen myxedematosus is a rare chronic, slowly progressive form of localized lichen myxedematosus (see this term) characterized by the development of a few to multiple small symmetrical skin-coloured mucinous papules on the limbs and trunk.
Papular mucinosis of infancy is a rare pediatric non progressive form of localized lichen myxedematosus (see this term) characterized by the development of firm opalescent mucinous papules on the upper arms and the trunk.
An Orphanet summary for this disease is currently under development. However, other data related to the disease are accessible from the Additional Information menu located on the right side of this page.
The term frontonasal dysplasia was coined by Sedano et al. (1970) to describe a constellation of findings limited to the face and head. The disorder is defined as 2 or more of the following: (1) true ocular hypertelorism; (2) broadening of the nasal root; (3) median facial cleft affecting the nose and/or upper lip and palate; (4) unilateral or bilateral clefting of the alae nasi; (5) lack of formation of the nasal tip; (6) anterior cranium bifidum occultum (see 168500); and (7) a V-shaped or widow's peak frontal hairline (Sedano and Gorlin, 1988). Most reported cases are sporadic, but a few familial cases have been reported. Twigg et al. (2009) characterized frontonasal malformation (FNM) as a 'very heterogeneous group of disorders' and summarized clinical features. Also see acromelic frontonasal dysplasia (AFND; 603671), frontofacionasal dysplasia (FFND; 229400), oculoauriculofrontonasal syndrome (OAFNS; 601452), the acrofrontofacionasal dysostosis syndromes (201180, 239710), and craniofrontonasal syndrome (304110). Genetic Heterogeneity of Frontonasal Dysplasia Frontonasal dysplasia-2 (FND2; 613451) is caused by mutation in the ALX4 gene (605420) on chromosome 11p11. Frontonasal dysplasia-3 (FND3; 613456) is caused by mutation in the ALX1 gene (601527) on chromosome 12q21.
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
Pertuzumab is a monoclonal antibody used in the treatment of breast cancer. It targets a receptor in the epidermal growth factor family encoded by the ERBB2 gene, which is commonly referred to as the HER2 gene. The HER2 gene is overexpressed in 15-20% of breast cancers and is also overexpressed in some cases of other cancer types (gastric, colon, head and neck). Overall, “HER2 positive” tumors are associated with a faster rate of growth and a poorer prognosis. The use of pertuzumab in treatment regimens for breast cancer improves outcomes, but adverse effects of therapy include cardiac toxicity. The FDA-approved drug label for pertuzumab states that pertuzumab should only be used to treat patients with tumors which have either HER2 protein overexpression or HER2 gene amplification, as determined by an accurate and validated FDA-approved assay. This is because these are the only patients studied for whom benefit has been shown. A guideline from ASCO/CAP states that oncologists must request HER2 testing on every primary invasive breast cancer (and on a metastatic site, if stage IV and if specimen available) from a patient with breast cancer to guide decision to pursue HER2-targeted therapy. This should be especially considered for a patient who previously tested HER2 negative in a primary tumor and presents with disease recurrence with clinical behavior suggestive of HER2-positive or triple-negative disease.
Ring chromosome 14 syndrome is characterized by early-onset epilepsy, developmental delay with mental retardation and poor speech, microcephaly, and dysmorphic facial features. Additional variable features include hypotonia and retinopathy (summary by Imataka et al., 2013 and Giovannini et al., 2013).
Simeprevir is a hepatitis C virus (HCV) protease inhibitor used in combination with other drugs to treat chronic hepatitis genotype 1 or 4 infection. Previously, the standard care of patients with HCV infection was peginterferon alfa and ribavirin, but ~40-50% of patients with HCV genotype 1 infection had a suboptimal sustained virological response (SVR. A SVR is defined as undetectable HCV RNA by the end of treatment and at a specific number of weeks after the end of treatment. The addition of simeprevir increased the SVR in patients with HCV genotype 1 infection who were previously untreated. However, there were reports of treatment failure, most commonly in adults, who failed to respond to previous peginterferon and ribavirin treatment. The FDA-approved drug label for simeprevir contains information regarding a genetic variant near the IFNL3 gene (a C to T change; rs12979860), which is a strong predictor of response to peginterferon alfa and ribavirin treatment. The label states that in phase 3 clinical trials, SVR rates were lower in patients with CT and TT genotypes, compared to patients with the CC genotype. However, patients of all IFNL3 genotypes had highest SVR rates when being treated with regimens that included simeprevir. In addition, the label strongly recommends patients with HCV genotype 1a infection should be screened for the presence of virus with the S3 Q80K polymorphism. If Q80K is detected, the label strongly recommends that alternative therapy be considered.
Clozapine is one of the most effective antipsychotics available in the treatment of schizophrenia and the only antipsychotic found to be effective in treatment-resistant schizophrenia. Clozapine is also used to reduce the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. Compared to typical antipsychotics, clozapine is far less likely to cause movement disorders, known as extrapyramidal side effects, which include dystonia, akathisia, parkinsonism, and tardive dyskinesia. However, there are significant risks associated with clozapine therapy that limits its use to only the most severely ill patients who have not responded adequately to standard drug therapy. Most notably, because of the risk of clozapine-induced agranulocytosis, clozapine treatment requires monitoring of white blood counts and absolute neutrophil counts, and in the US, the FDA requires that patients receiving clozapine be enrolled in a computer-based registry. Clozapine is metabolized in the liver by the cytochrome P450 (CYP) system of enzymes. CYP1A2 is the main CYP isoform in clozapine metabolism and CYP1A2 activity is an important determinant of clozapine dose. Other CYP enzymes involved in clozapine metabolism include CYP2D6 and CYP3A4. Approximately 6-10% of Caucasians have reduced activity of CYP2D6 (""poor metabolizers""). These individuals may develop higher than expected plasma concentrations of clozapine with usual doses. The FDA-approved drug label for clozapine states that a dose reduction may be necessary in patients who are CYP2D6 poor metabolizers.
Acute necrotizing encephalopathy type 1, also known as susceptibility to infection-induced acute encephalopathy 3 or IIAE3, is a rare type of brain disease (encephalopathy) that occurs following a viral infection such as the flu.Acute necrotizing encephalopathy type 1 typically appears in infancy or early childhood, although some people do not develop the condition until adolescence or adulthood. People with this condition usually show typical symptoms of an infection, such as fever, cough, congestion, vomiting, and diarrhea, for a few days. Following these flu-like symptoms, affected individuals develop neurological problems, such as seizures, hallucinations, difficulty coordinating movements (ataxia), or abnormal muscle tone. Eventually, most affected individuals go into a coma, which usually lasts for a number of weeks. The condition is described as ""acute"" because the episodes of illness are time-limited.People with acute necrotizing encephalopathy type 1 develop areas of damage (lesions) in certain regions of the brain. As the condition progresses, these brain regions develop swelling (edema), bleeding (hemorrhage), and then tissue death (necrosis). The progressive brain damage and tissue loss results in encephalopathy.Approximately one-third of individuals with acute necrotizing encephalopathy type 1 do not survive their illness and subsequent neurological decline. Of those who do survive, about half have permanent brain damage due to tissue necrosis, resulting in impairments in walking, speech, and other basic functions. Over time, many of these skills may be regained, but the loss of brain tissue is permanent. Other individuals who survive their illness appear to recover completely.It is estimated that half of individuals with acute necrotizing encephalopathy type 1 are susceptible to recurrent episodes and will have another infection that results in neurological decline; some people may have numerous episodes throughout their lives. Neurological function worsens following each episode as more brain tissue is damaged.
Dysmorphism-pectus carinatum-joint laxity syndrome is characterised by joint laxity, pectus carinatum and facial dysmorphism (mild frontal bossing, a beaked nose with a low nasal bridge, malar hypoplasia, chubby cheeks, a striking philtrum and arched upper lips). It has been described in two siblings. The mode of transmission is unknown.
Mild phosphoribosylpyrophosphate (PRPP) synthetase superactivity is the mild and late-onset form of PRPP synthetase superactivity (see this term), an X-linked disorder of purine metabolism associated with hyperuricemia and hyperuricosuria, leading to urolithiasis and gout. This form is not associated with any neuropathy or central nervous system (CNS) disorders.
Severe phosphoribosylpyrophosphate (PRPP) synthetase superactivity is the severe and early-onset form of PRPP synthetase superactivity (see this term), an X-linked disorder of purine metabolism associated with hyperuricemia and hyperuricosuria, that is characterized by urolithiasis, gout and neurodevelopmental anomalies.
Hereditary late-onset Parkinson disease (LOPD) is a form of Parkinson disease (PD), characterized by an age of onset of more than 50 years, tremor at rest, gait complaints and falls, bradykinesia, rigidity and painful cramps. Patients usually present a low risk of developing non motor symptoms, dystonia, dyskinesia and levodopa-induced dyskinesia (LID).
Generalized eruptive keratoacanthoma (GEKA) is rare variant of keratoacanthoma (KA) that affects the skin and mucous membranes and which is characterized by a sudden generalized eruption of severely pruritic, hundreds to thousands of small follicular papules, often with a central keratotic plug.
Spinocerebellar ataxia type 40 (SCA40) is a very rare subtype of autosomal dominant cerebellar ataxia type 1, characterized by the adult-onset of unsteady gait and dysarthria, followed by wide-based gait, gait ataxia, ocular dysmetria, intention tremor, scanning speech, hyperreflexia and dysdiadochokinesis.
Spinocerebellar ataxia type 38 (SCA38) is a subtype of autosomal dominant cerebellar ataxia type 3 characterized by the adult-onset (average age: 40 years) of truncal ataxia, gait disturbance and gaze-evoked nystagmus. The disease is slowly progressive with dysarthria and limb ataxia following. Additional manifestations include diplopia and axonal neuropathy.
Mucolipidosis III alpha/beta (MLIII alpha/beta) is a lysosomal disorder characterized by progressive slowing of the growth rate from early childhood, stiffness and pain in joints, gradual coarsening of facial features, moderate developmental delay and mild intellectual disability in most patients.
#945;-fetoprotein and intrauterine growth restriction is observed in routine pregnancy examination.
Microcephaly-complex motor and sensory axonal neuropathy syndrome is an extremely rare subtype of hereditary motor and sensory neuropathy characterized by severe, rapidly-progressing, distal, symmetric polyneuropathy and microcephaly (which can be evident in utero) with intact cognition. Clinically it presents with delayed motor development, hypotonia, absent or reduced deep tendon reflexes, progressive muscle wasting and weakness and scoliosis.
Urachal sinus is a type of congenital urachal anomaly (see this term) resulting from the failure of the umbilical end of the urachus to close, without continuity to the bladder, and that is usually asymptomatic but can present with continuous cloudy umbilical discharge, tender midline infraumbilical mass and fever when infected.
Urachal diverticulum is the rarest type of congenital urachal anomaly (see this term) resulting from the failure of the distal urachus to close at its point of connectivity to the bladder that is usually asymptomatic but can be associated with recurrent urinary tract infections and other complications.
Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD and/or PCH) constitutes a rare subgroup of pulmonary arterial hypertension (PAH; see this term) characterized by obliterative fibrosis of the small pulmonary veins and venules and/or capillary infiltration of the pulmonary interstitium leading to increased pulmonary vascular resistance and right ventricular dysfunction.
Secondary polyarteritis nodosa (PAN) is a rare serious form of PAN (see this term) characterized by vasculitis in a background of viral infection, primarily with hepatitis B virus (HBV).
Hereditary nonpolyposis colon cancer (HNPCC) is a cancer-predisposing condition characterized by the development of colorectal cancer not associated with colorectal polyposis, endometrial cancer, and various other cancers (such as malignant epithelial tumor of ovary, gastric, biliary tract, small bowel, and urinary tract cancer) that are frequently diagnosed at an early age.
mosquito-born virus disease characterized by a clinical course that may be asymptomatic or mild with fever, conjunctivitis, muscle and joint pain, headache, exanthema, but may also be associated with severe neurological (meningitis, meningoencephalitis and myelitis) and auto-immune (Guillain-Barre syndrome) complications, as well as a potential increase of birth defects (microcephaly) if the infection occurs during pregnancy.
Brachyolmia, recessive type is a form of brachyolmia (see this term), a group of rare genetic skeletal disorders, characterized by short-trunked short stature with platyspondyly and scoliosis. Corneal opacities and precocious calcification of the costal cartilage are rare syndromic components. Premature pubarche may occur.
Corticobasal syndrome (CBS) is a rare neurodegenerative disease characterized by multifaceted motor system dysfunctions and cognitive defects such as asymmetric rigidity, bradykinesia, limb apraxia, and visuospatial dysfunction.
The zona pellucida is a glycoprotein matrix that surrounds oocytes and has an average thickness of 17 micrometers. It is vital for the production of oocytes in early development, for fertilization, and for protection of early embryos before implantation. Absence of the zona pellucida in OOMD1 results in sterility (summary by Huang et al., 2014). Genetic Heterogeneity of Oocyte Maturation Defects Also see OOMD2 (616780), caused by mutation in the TUBB8 gene (616768) on chromosome 10p15; OOMD3 (617712), caused by mutation in the ZP3 gene (182889) on chromosome 7q11; OOMD4 (617743), caused by mutation in the PATL2 gene (614661) on chromosome 15q21; OOMD5 (617996), caused by mutation in the WEE2 gene (614084) on chromosome 7q34; and OOMD6 (618353), caused by mutation in the ZP2 gene (182888) on chromosome 16p12.
Sofosbuvir is an antiviral agent used in the treatment of chronic hepatitis C virus (HCV) infection. Sofosbuvir is FDA-approved to treat patients infected with HCV genotypes 1, 2, 3, and 4, as part of a combination antiviral treatment regimen. HCV genotype 1 is the most prevalent worldwide and HCV genotype 3 is the next most prevalent. Sofosbuvir may also be used as part of the treatment regimen of HCV genotypes 5 or 6. About 180 million people worldwide are infected with chronic hepatitis C, which is a major cause of chronic liver disease, cirrhosis, and liver cancer. Viral eradication is suboptimal with peginterferon plus ribavirin-based therapy, with only about half of patients with HCV genotype 1 infection achieving a sustained virological response (SVR) after 24 weeks. A SVR is defined as undetectable HCV RNA by the end of treatment or at a specific number of weeks after the initiation of treatment, e.g., undetectable HCV RNA at 12 weeks is annotated (SVR12). Direct-acting antivirals (DAAs), such as sofosbuvir, were developed to improve viral eradication rates. They target HCV-encoded proteins involved in viral replication and infection. Sofosbuvir, the first and thus far only DAA, targets NS5B polymerase, the viral enzyme required for HCV RNA replication. Sofosbuvir may be used in combination with peginterferon. The genetic variant rs12979860, located in the INFL4 gene, is a strong predictor of response to peginterferon-based therapies. The variant is a C to T change—individuals with the favorable ""C/C"" genotype have about a 2-fold higher likelihood of achieving SVR compared to individuals with CT or TT genotypes. (Note, because the association of rs12979860 with treatment response was reported several years before the discovery of IFNL4, the variant is commonly, but mistakenly, referred to as IL28B, which is the previous name for the IFNL3 gene.) For specific treatment regimens that include sofosbuvir, although the IFNL4 variant still influences treatment outcomes, the SVR remains relatively high for all IFNL4 genotypes. For example in the NEUTRINO study, which is referred to in the FDA-approved drug label for sofosbuvir, the SVR12 rate was 99% in individuals with baseline C/C alleles and 87% in individuals with baseline non-C/C alleles. The individuals in this study had HCV genotype 1 or 4 infection, and were receiving sofosbuvir plus peginterferon plus ribavirin therapy. The drug label for sofosbuvir also discusses viral resistance. In cell culture, the amino acid substitution S282T in the viral NS5B polymerase is associated with reduced susceptibility to sofosbuvir. During the ELECTRON trial, this substitution was transiently detected in one individual who relapsed during sofosbuvir monotherapy. However, the clinical significance of such substitutions remains unknown.
Congenital mirror movement disorder is a condition in which intentional movements of one side of the body are mirrored by involuntary movements of the other side. For example, when an affected individual makes a fist with the right hand, the left hand makes a similar movement. The mirror movements in this disorder primarily involve the upper limbs, especially the hands and fingers. This pattern of movements is present from infancy or early childhood and usually persists throughout life, without other associated signs and symptoms. Intelligence and lifespan are not affected.People with congenital mirror movement disorder can have some difficulty with certain activities of daily living, particularly with those requiring different movements in each hand, such as typing on a keyboard. They may experience discomfort or pain in the upper limbs during prolonged use of the hands.The extent of the mirror movements in this disorder can vary, even within the same family. In most cases, the involuntary movements are noticeable but less pronounced than the corresponding voluntary movements. The extent of the movements typically stay the same throughout the lifetime of an affected individual.Mirror movements can also occur in people who do not have congenital mirror movement disorder. Mild mirror movements are common during the normal development of young children and typically disappear before age 7. They can also develop later in life in people with neurodegenerative disorders such as Parkinson disease. Mirror movements may also be present in certain other conditions with a wider range of signs and symptoms (syndromes).
Isolated cleft lip is a fissure type embryopathy extending from the upper lip to the nasal base.
Prasugrel is a third-generation thienopyridine platelet inhibitor used in the management of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prasugrel is used to reduce thrombotic cardiovascular events, such as stent thrombosis, myocardial infarction, and stroke in these patients. Prasugrel, along with other antiplatelet agents such as clopidogrel and ticagrelor, inhibits platelet activation by irreversibly binding to the platelet receptor, P2RY12. Prasugrel is metabolized to its active metabolite primarily by CYP3A5 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19. The FDA-approved label for prasugrel states that genetic variations in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 genes do not have a relevant effect on prasugrel pharmacokinetics and the generation of its active metabolite or its inhibition of platelet aggregation in healthy subjects, patients with stable atherosclerosis, or ACS. Another commonly prescribed antiplatelet is the second-generation thienopyridine clopidogrel, which is bioactivated primarily by CYP2C19. Consequently, clopidogrel is less effective among patients with decreased or no function variant alleles in the CYP2C19 gene. In contrast, CYP2C19 variants are not associated with a decrease in effectiveness of prasugrel, which is a more potent antiplatelet agent than clopidogrel, but has a higher risk of bleeding.
Multicentric osteolysis, nodulosis, and arthropathy (MONA) describes a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. MONA includes a condition formerly called nodulosis-arthropathy-osteolysis (NAO) syndrome. It may also include a similar disorder called Torg syndrome, although it is unknown whether Torg syndrome is actually part of MONA or a separate disorder caused by a mutation in a different gene.In most cases of MONA, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities can later spread to other areas of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with MONA develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature.Many affected individuals develop subcutaneous nodules, which are firm lumps of noncancerous tissue underneath the skin, especially on the soles of the feet. Some affected individuals also have skin abnormalities including patches of dark, thick, and leathery skin. Other features of MONA can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as ""coarse.""
17-beta hydroxysteroid dehydrogenase 3 deficiency is a condition that affects male sexual development. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a male sex hormone (androgen) called testosterone. Testosterone has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth.Most people with 17-beta hydroxysteroid dehydrogenase 3 deficiency are born with external genitalia that appear female. In some cases, the external genitalia do not look clearly male or clearly female (sometimes called ambiguous genitalia). Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis (micropenis) or the urethra opening on the underside of the penis (hypospadias).During puberty, people with this condition develop some male secondary sex characteristics, such as increased muscle mass, deepening of the voice, and development of male pattern facial and body hair. In addition to these changes typical of adolescent boys, some affected individuals may also experience breast enlargement (gynecomastia). Despite having testes, people with this disorder are generally unable to father children (infertile).Children with 17-beta hydroxysteroid dehydrogenase 3 deficiency are often raised as girls. About half of these individuals adopt a male gender role in adolescence or early adulthood.
Cornelia de Lange syndrome is a developmental disorder that affects many parts of the body. The features of this disorder vary widely among affected individuals and range from relatively mild to severe.Cornelia de Lange syndrome is characterized by slow growth before and after birth leading to short stature; intellectual disability that is usually moderate to severe; and abnormalities of bones in the arms, hands, and fingers. Most people with Cornelia de Lange syndrome also have distinctive facial features, including arched eyebrows that often meet in the middle (synophrys), long eyelashes, low-set ears, small and widely spaced teeth, and a small and upturned nose. Many affected individuals also have behavior problems similar to autism, a developmental condition that affects communication and social interaction.Additional signs and symptoms of Cornelia de Lange syndrome can include excessive body hair (hypertrichosis), an unusually small head (microcephaly), hearing loss, and problems with the digestive tract. Some people with this condition are born with an opening in the roof of the mouth called a cleft palate. Seizures, heart defects, and eye problems have also been reported in people with this condition.
Vemurafenib is a kinase inhibitor used in the treatment of patients with unresectable or metastatic melanoma with the BRAF V600E variant. BRAF is an intracellular kinase in the mitogen-activated protein kinases (MAPK) pathway. BRAF is involved in regulating important cell functions such as cell growth, division, differentiation, and apoptosis. BRAF is also a proto-oncogene—when mutated it has the ability to transform normal cells into cancerous cells. Variation in the kinase domain of BRAF have been associated with various cancers. The most common BRAF variant, V600E, constitutively activates the kinase, and causes cell proliferation in the absence of growth factors that would normally be required. The V600E variant is detected in approximately 50% of melanomas. The FDA-approved drug label for vemurafenib states that the presence of BRAF V600E mutation in tumor specimens should be confirmed, using an FDA-approved test, before starting treatment with vemurafenib. The label also states that vemurafenib is not indicated for treatment of patients with wild-type BRAF melanoma. Variations in NRAS, also an oncogene, are found in up to 30% of all malignancies and in approximately 15-20% of melanomas. NRAS variants activate MAPK and have been implicated in in acquired resistance to BRAF inhibitors. Vemurafenib’s label warns that one adverse effect associated with therapy may be the progression of pre-existing chronic myelomonocytic leukemia with NRAS mutation. Other adverse effects include arthralgia, rash, alopecia, photosensitivity reaction, pruritus, and skin papilloma.
Dabrafenib is a kinase inhibitor used in the treatment of patients with unresectable or metastatic melanoma with specific BRAF variants. Dabrafenib can be used as a single agent to treat melanoma with the BRAF V600E variant, or in combination with the MEK inhibitor trametinib to treat melanoma with BRAF V600E or V600K variants. BRAF is an intracellular kinase in the mitogen-activated protein kinases (MAPK) pathway. BRAF is involved in regulating important cell functions such as cell growth, division, differentiation, and apoptosis. BRAF is also a proto-oncogene—when mutated it has the ability to transform normal cells into cancerous cells. Variation in the kinase domain of BRAF have been associated with various cancers. The most common BRAF variant, V600E, constitutively activates the kinase, and causes cell proliferation in the absence of growth factors that would normally be required. The V600E variant is detected in approximately 50% of melanomas. The FDA-approved label for dabrafenib states that the presence of BRAF mutation in tumor specimens (V600E for dabrafenib monotherapy; V600E or V600K for dabrafenib plus trametinib) should be confirmed, using an FDA-approved test, before starting treatment with dabrafenib. Dabrafenib is not indicated for treatment of patients with wild-type BRAF melanoma. The label also states that patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency should be monitored for signs of hemolytic anemia while taking dabrafenib.
In humans and primates, NR1H5P is a pseudogene. However, in other mammals, it encodes a functional nuclear hormone receptor that appears to be involved in cholesterol biosynthesis (Otte et al., 2003).
Single-organ polyarteritis nodosa (PAN) is a rare, often mild form of PAN characterized by limited disease without generalized manifestations, most often affecting the skin (cutaneous PAN; see this term), the brain, eyes, pancreas, testicles, ureter, breasts, or ovaries. Affected patients are often younger than those with systemic PAN (see this term) and relapses appear to be more common.
Clear cell sarcoma of kidney is a rare, primary, genetic renal tumor usually characterized by a unilateral, unicentric, morphologically diverse tumor that arises from the renal medulla and has a tendency for vascular invasion. Clinically it presents with a palpable abdominal mass, abdominal or flank pain, hematuria, anemia and/or fatigue. Metastatic spread to lymph nodes, bones, lungs, retroperitoneum, brain and liver is common at time of diagnosis and therefore bone pain, cough or neurological compromise may be associated. Metastases to unusual sites, such as the scalp, neck, nasopharynx, axilla, orbits and epidural space, have been reported.
Systemic polyarteritis nodosa (PAN; see this term) is a chronic systemic necrotizingvasculitis of adults and childrenaffecting small- and medium-sized vessels and characterized by formation of microaneurysms leading to serious generalized disease and multi-organ involvement.
Pelger-Huet anomaly with mild skeletal anomalies is characterized by abnormal nuclear shape and chromatin organization in blood granulocytes (PHA), short stature, and mild skeletal anomalies (Hoffmann et al., 2002; Borovik et al., 2013). Initial skeletal features may improve with age (Sobreira et al., 2014).
Humerofemoral hypoplasia with radiotibial ray deficiency is a severe dysostosis characterized by reduction of all 4 limbs as well as hypoplasia of the upper limb girdle and pelvis. Rudimentary finger- or toe-like appendages may be present (Szenker-Ravi et al., 2018).
Glycosylphosphatidylinositol biosynthesis defect-17 is an autosomal recessive disorder characterized by variable neurologic deficits that become apparent in infancy or early childhood. Patients may present with early-onset febrile or afebrile seizures that tend to be mild or controllable. Other features may include learning disabilities, autism, behavioral abnormalities, hypotonia, and motor deficits. The phenotype is relatively mild compared to that of other GPIBDs (summary by Nguyen et al., 2018). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Tetraamelia syndrome-2 (TETAMS2) is characterized by rudimentary appendages or complete absence of the limbs, usually symmetric, as well as bilateral agenesis of the lungs. There are abnormalities of the pulmonary vasculature and dysmorphic features, including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, microretrognathia, and labioscrotal fold aplasia (Szenker-Ravi et al., 2018). For a discussion of genetic heterogeneity of TETAMS, see 273395.
NOTCH2NLR appears to be a nonfunctional pseudogene derived from a partial duplication of the NOTCH2 gene (600275) (Fiddes et al., 2018).
PPCD4 is characterized by an irregular posterior corneal surface with occasional opacities of variable size and shape. There is inter- and intrafamilial as well as intraindividual variability. Symptoms can include blurred vision due to corneal edema, reduced visual acuity, secondary glaucoma, and corectopia; some affected individuals are asymptomatic. Rare patients have undergone enucleation for painful eye (Liskova et al., 2018). For a discussion of genetic heterogeneity of PPCD, see 122000.
Coffin-Siris syndrome-7 is an autosomal dominant neurodevelopmental disorder characterized by global developmental delay with mild to moderate intellectual disability, speech impairment, behavioral abnormalities, poor overall growth, coarse facial features, and hypoplastic fifth toenails (summary by Vasileiou et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Charcot-Marie-Tooth disease type 2DD is an autosomal dominant peripheral sensorimotor neuropathy mainly affecting the lower limbs. Affected individuals have gait impairment due to distal muscle weakness and atrophy. Some patients may also have involvement of the distal upper limbs, resulting in atrophy of the intrinsic hand muscles. The age at onset and severity of the disorder is highly variable, even within families, and those with earlier onset in late childhood or the teenage years tend to have a more severe disease course. Patients remain ambulatory even late in the disease, although some may require orthotic devices (summary by Lassuthova et al., 2018). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (118210).
Lesinurad (brand name Zurampic) is a urate transport inhibitor used in the treatment of gout. Gout is one of the most common types of inflammatory arthritis, affecting approximately 3% of adults worldwide. It is caused by the accumulation of urate crystals in joints. The long-term management of gout includes reducing risk factors (e.g., obesity, alcohol use, diuretic use, poor renal function), and medication to lower uric acid levels. Lesinurad reduces the high level of uric acid (hyperuricemia) associated with gout. Lesinurad should only be used in combination with a xanthine oxidase inhibitor (e.g., allopurinol, febuxostat) –– the risk of acute renal failure is increased if lesinurad is used alone. The addition of lesinurad to gout treatment is reserved for patients who have failed to achieve their target uric acid level despite being treated with a xanthine oxidase inhibitor. Xanthine oxidase inhibitors reduce uric acid by inhibiting its production, whereas lesinurad reduces uric acid by blocking its reabsorption in the kidney. Lesinurad is primarily metabolized by CYP2C9 to several inactive metabolites. Individuals who lack CYP2C9 activity (""CYP2C9 poor metabolizers"") have an increased exposure to lesinurad, and an increased risk of side effects. Adverse reactions of lesinurad therapy include kidney stones and other kidney problems. Lesinurad is also associated with an increased risk of cardiovascular events. The FDA-approved drug label for lesinurad states that lesinurad should be used with caution in CYP2C9 poor metabolizers, but does not provide specific dose adjustments in this group. The standard dose of lesinurad is 200 mg daily. Lesinurad is contraindicated in patients with severe impairment of kidney function (e.g., kidney transplant and hemodialysis patients) as well as individuals with tumor lysis syndrome or Lesch-Nyhan syndrome.
PKDYS2 is an autosomal recessive complex infantile-onset neurologic disorder characterized by abnormal movements, including parkinsonism, dystonia, and poor fine motor skills, as well as autonomic dysfunction, including abnormal sweating, cold extremities, and poor sleep. Some patients have variable degrees of developmental delay. Features of the disorder are consistent with decreased levels of monoamine neurotransmitters, although levels of these in the spinal fluid are normal. Preliminary findings indicate that treatment with a dopamine receptor agonist results in dramatic and sustained clinical improvement (summary by Rilstone et al., 2013). For a discussion of genetic heterogeneity of PKDYS, see 613135.
Pulmonary alveolar proteinosis with hypogammaglobulinemia (PAPHG) is primarily a lung disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis in the first months of life. Affected individuals have normal respiratory function at birth. Development of the disorder appears to be influenced or triggered by viral infection, manifest as progressive respiratory insufficiency, confluent consolidations on lung imaging, and diffuse collection of periodic acid-Schiff (PAS)-positive material in pulmonary alveoli associated with small and nonfoamy alveolar macrophages. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly. Many patients die of respiratory failure in infancy or early childhood; hematopoietic stem cell transplantation may be curative. The pathogenesis may be related to abnormal function of alveolar macrophages, resulting in decreased catabolism of surfactant (summary by Cho et al., 2018)
MRD57 is an autosomal dominant neurodevelopmental disorder with a highly variable phenotype. Most affected individuals have delayed psychomotor development apparent in infancy or early childhood, language delay, and behavioral abnormalities. Additional features may include hypotonia, feeding problems, gastrointestinal issues, and dysmorphic facial features (summary by Reijnders et al., 2018).
CMH27 is a severe, early-onset cardiomyopathy with morphologic features of both dilated and hypertrophic disease, characterized by biventricular involvement and atypical distribution of hypertrophy. Heterozygotes are at increased risk of developing cardiomyopathy (Almomani et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of hypertrophic cardiomyopathy, see CMH1 (192600). An oligogenic form of hypertrophic cardiomyopathy, involving heterozygous mutations in the ALPK3, TTN (188840), and MYL3 (160790) genes has also been reported in 1 family.
Proteasome-associated autoinflammatory syndrome-3 is an autosomal recessive syndrome with onset in early infancy. Affected individuals present with nodular dermatitis, recurrent fever, myositis, panniculitis-induced lipodystrophy, lymphadenopathy, and dysregulation of the immune response, particularly associated with abnormal type I interferon-induced gene expression patterns. Additional features are highly variable, but may include joint contractures, hepatosplenomegaly, anemia, thrombocytopenia, recurrent infections, autoantibodies, and hypergammaglobulinemia. Some patients may have intracranial calcifications (summary by Brehm et al., 2015). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).
Proteasome-associated autoinflammatory syndrome-2 is an autosomal dominant disorder with onset in early infancy. Affected individuals develop severe inflammatory neutrophilic dermatitis, autoimmunity, and variable immunodeficiency (summary by Poli et al., 2018). For a discussion of genetic heterogeneity of PRAAS, see PRAAS1 (256040).
Carboxylesterase-1 (114835) is a widely expressed serine esterase that is involved in the hydrolysis of multiple amide-containing and ester-containing endogenous and xenobiotic compounds including therapeutic agents such as methylphenidate, oseltamivir, angiotensin-converting enzyme inhibitors (e.g., trandolapril and temocapril), and anticancer drugs (e.g., capecitabin). In addition, CES1 is the primary enzyme responsible for metabolizing clopidogrel and its derivatives (summary by Lewis et al., 2013).
Polycystic kidney disease-6 is an autosomal dominant renal disease characterized by the development of multiple small renal cysts and progression to renal insufficiency or end-stage renal disease (ESRD) most often after the sixth decade. The cysts are generally small (less than 1 to 3 cm) and the kidneys are not massively enlarged. Some patients may have evidence of chronic interstitial fibrosis and about half develop liver cysts (summary by Cornec-Le Gall et al., 2018). For a discussion of genetic heterogeneity of polycystic kidney disease, see PKD1 (173900).
Pontocerebellar hypoplasia type 1D is a severe autosomal recessive neurologic disorder characterized by severe hypotonia and a motor neuronopathy apparent at birth or in infancy. Patients have respiratory insufficiency, feeding difficulties, and severely delayed or minimal gross motor development. Other features may include eye movement abnormalities, poor overall growth, contractures. Brain imaging shows progressive cerebellar atrophy with relative sparing of the brainstem (summary by Burns et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1A (607596).
Primary ciliary dyskinesia-38 is an autosomal recessive disorder characterized by chronic airway disease and recurrent sinopulmonary infections beginning in infancy and caused by defective ciliary function. Affected individuals often have neonatal respiratory distress and may later have infertility. About half of patients have laterality defects due to ciliary dysfunction in early embryonic development (summary by Fassad et al., 2018 and Hoben et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see CILD1 (244400).
Osteogenesis imperfecta type XIX (OI19) is characterized by prenatal fractures and generalized osteopenia, with severe short stature in adulthood, as well as variable scoliosis and pectal deformity, and marked anterior angulation of the tibia (Lindert et al., 2016).
Inflammatory bowel disease is a chronic inflammatory condition of the gastrointestinal tract (summary by Mohanan et al., 2018). For a general description and a discussion of genetic heterogeneity of inflammatory bowel disease, including Crohn disease (CD) and ulcerative colitis (UC), see IBD1 (266600).
Ovarian dysgenesis-6 is characterized by absence of spontaneous pubertal development in females with elevated gonadotropin levels, small uterus, and absence of ovarian tissue on imaging studies. Males appear to be unaffected (Weinberg-Shukron et al., 2015). For a discussion of genetic heterogeneity of ovarian dysgenesis, see ODG1 (233300).
LDLCQ8 is a quantitative trait affecting LDL cholesterol levels that is effected through the LIMA1 gene, which has a key role in intestinal cholesterol absorption. Individuals with LIMA1 mutations that impair protein function have reduced plasma LDL cholesterol levels and reduced cholesterol absorption (Zhang et al., 2018).
Peeling skin syndrome-6 is characterized by generalized ichthyotic dry skin and bullous peeling lesions on the trunk and limbs at sites of minor trauma. There is residual hyperpigmentation in areas of healing, but no scarring. Skin symptoms are exacerbated by warmth and humidity; however, the disorder improves markedly with age (Bolling et al., 2018; Mohamad et al., 2018). For a discussion of genetic heterogeneity of peeling skin syndrome, see PSS1 (270300).
Spermatogenic failure-28 is characterized by nonobstructive azoospermia, with a Sertoli cell-only phenotype observed in testicular tissue (Kasak et al., 2018). For a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Spermatogenic failure-29 is characterized by nonobstructive azoospermia or oligozoospermia. Sperm that are present are immotile and exhibit abnormal morphology, primarily defects of the acrosome and head-neck junction (Kherraf et al., 2017). For a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
A lack of coordination of leg movement manifested by undershoot or overshoot of the intended position of the leg.
A lack of coordination of arm movement manifested by undershoot or overshoot of the intended position of the arm.
A postural abnormality characterized by the inability to stand without external support despite having sufficient muscle strength.
Elongation, dilatation, and/or tortuosity of the vertebrobasilar segment. The definition of VBD includes: (i) diameter of basilar or vertebral artery over 4.5 mm; or (ii) deviation of any portion more than 10 mm from the shortest expected course; and (iii) length of basilar artery over 29.5 mm or length of intracranial vertebral artery over 23.5 mm.
A type of incomitant strabismus in which both elevator muscles (i.e., the inferior oblique and superior rectus muscles) of the same eye are weak leading to restricted elevation and hypotropia.
An ocular movement abnormality characterised by simultaneous weakness of the inferior rectus muscle and superior oblique muscle of the same eye.
A type of incomitant strabismus in which the angle of deviation varies as the patient's gaze shifts upwards and/or downwards.
A manifest or latent ocular deviation in which one or other eye tends to deviate nasally.
A form of esotropia (convergent deviation of the eyes) associated with activation of the accommodative reflex.
Any structural anomaly of a cell of the monocyte, granulocyte, mast cell, megakaryocyte, or erythroid lineage.
A reduction in the numbers of pro-B cells (defined by coexpression of CD34 and CD19). Earlier B-cell precursors are defined by expressing surface CD34 and cytoplasmic TdT in the absence of CD19.
A manifest or latent ocular deviation in which one or other eye tends to deviate temporally.
Lamellar cataracts with associated linear lens opacities radially extending towards the periphery of the lens.
A type of cataract characterised by club-shaped and dot opacities distributed radially in the deep cortex. These lens opacities surround the nucleus in an appearance that is though to resemble a crown.
Tiny deposits corresponding to cells floating in the anterior chamber of the eye. This appearance is typically associated with intraocular inflammation leading to breakdown of the blood-aqueous barrier and resulting in an increase in the number of cells and in the aqueous humor. Grading (SUN Working Group) is performed by estimating the number of cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp.
Anterior chamber cells with 6-15 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp.
Anterior chamber cells with 1-5 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp.
Anterior chamber cells with less than one cell in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp.
Anterior chamber cells with 16-25 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp.
Anterior chamber cells with 26-50 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp.
Anterior chamber cells with more than 50 cells in a 1 mm by 1 mm slit beam field, employing adequate light intensity and magnification on a slit lamp.
An anomaly of the retina with serous detachment of the neurosensory retina secondary to one or more focal lesions of the retinal pigment epithelium (RPE), and associated with blurred vision, usually in one eye only and perceived typically by the patient as a dark spot in the centre of the visual field with associated micropsia and metamorphopsia. Normal vision often recurs spontaneously within a few months.
The presence of aneurysmal polypoidal lesions in the choroidal vasculature. The aneurysmal dilatations, also known as polyps, may be found at subfoveal, juxtafoveal, extrafoveal, peripapillary or even peripheral regions. These polypoidal dilatations may be visible as reddish-orange subretinal nodules during ophthalmoscopic examination. The polypoidal lesions are best detected on indocyanine green angiography (ICGA) and might be associated with a branching vascular network (BVN) of neovascularization.
Increased tendency of choiroidal blood vessels to allow fluids to leak characterized by multifocal choroidal hyperfluorescence on indocyanine green angiography (ICGA).
A type of cataract that shows a spectacular display of multiple colours that glitters with the change of incident light like an illuminated Christmas tree.
Punctal stenosis is a condition in which the external opening of the lacrimal canaliculus is narrowed or occluded.
A mild form of myopia with up to -3.00 diopters.
Any structural anomaly of the principal vein draining blood from the upper portion of the body and delivering it to the right ventricle of the heart.
Any structural anomaly of the principal vein draining blood from the lower portion of the body.
Aortic valve prolapse can be diagnosed when either or both of the right or non-coronary aortic valve cusps (seen in the cross sectional echocardiographic long axis view) show backward bowing towards the left ventricle beyond a line joining the points of attachment of the aortic valve leaflets to the annulus.
Any structural abnormality of the left atrium.
Any structural abnormality of the right atrium.
Bleeding between the neurosensory retina and the retinal pigment epithelium (RPE) arising from the choroidal or retinal circulation.
Golden, scintillating, particulate reflection noted on fundus examination (typically in the macula and sparing the fovea). The term tapetal is used to describe this 'metallic' sheen appearance as it is thought to be similar to the 'tapetal' reflex seen in the eyes of certain animals.
A form of manifest strabismus (heterotropia) in which one eye is deviated downwards when both eyes are open.
Tendency for the visual ais of one eye to be higher than that of the other.
A type of strabismus characterized by permanent upward deviation of the visual axis of one eye.
A type of strabismus in which the visual axis of one eye is higher than that of the other.
A type of strabismus in which the visual axis of one eye is lower than that of the other.
Cyclodeviation is defined as the rotation of an eyeball along the anteroposterior axis and cyclotropia as a misalignment of cyclodeviation between the two eyes.
A functional anomaly of the muscles of the eye.
A functional anomaly of the superior oblique muscle, a fusiform muscle that originates in the upper, medial side of the orbit. The superior oblique muscle abducts, depresses and internally rotates the eye, and is the only extraocular muscle innervated by the fourth cranial nerve.
Decreased strength of the superior oblique muscle.
Mechanical limitation of the range of movement of the superior oblique muscle.
An ocular motility abnormality characterized by an overacting superior oblique muscle resulting to vertical incomitance of the eyes in lateral gaze. On examination, this is commonly seen as a downshoot of the adducting eye occuring when gaze is directed into the field of action of the inferior oblique muscle, producing a greater downward excursion of the adducted eye than of the abducted eye.
Reduced ocular movement of the superior oblique muscle which improves on testing ductions, typically associated with neurogenic palsy.
A functional anomaly of the inferior oblique muscle, an extraocular muscle that has its origin on the maxillary bone just posterior to the inferior medial orbital rim and lateral to the nasolacrimal canal and that is innervated by the inferior branch of the oculomotor nerve.
Mechanical limitation of the range of movement of the inferior oblique muscle.
Decreased strength of the inferior oblique muscle.
A common ocular motility disorder characterized by vertical incomitance of the eyes in lateral gaze. In primary inferior oblique muscle overaction, an upshoot of the adducting eye occurs when gaze is directed into the field of action of the inferior oblique muscle, producing a greater upward excursion of the adducted eye than of the abducted eye.
A functional anomaly of the inferior rectus muscle, which is innervated by the inferior division of oculomotor nerve and functions in the depression, adduction, and lateral rotation (extortion) of the eye.
Decreased strength of the inferior rectus muscle.
Mechanical limitation of the range of movement of the inferior rectus muscle.
A functional anomaly of the superior rectus muscle, an extraocular muscle that is innervated by the superior division of the oculomotor nerve, and whose primary function is the elevation of the globe.
A schwannoma (benign, usually encapsulated slow growing tumor composed of Schwann cells) located in the orbit.
Delayed descent of the upper eyelid on downgaze. Also described by some authors as von Graefe sign.
A functional anomaly of the medial rectus muscle, an extraocular muscle that is innervated by the inferior division of the oculomotor nerve and whose sole action is the adduction of the eyeball.
An outward turning (eversion) or rotation of the eyelid margin (i.e., ectropion) caused by shortening or contraction of the anterior or middle lamellae related to scarring.
A type of blepharitis that affects the eyelid skin, base of the eyelashes, and the eyelash follicles.
A type of blepharitis that affects the meibomian glands and meobomian gland orifices. This abnormality can be associated with a spectrum of appearances ranging from meibomian seborrhoea (foaming meibomian gland secretions) and meibomianitis (inflamed meibomian glands), to chalazia.
A type of epicanthus in which more extensive epicanthal folds with their origins in the eyebrow cover, pass in front of and lateral to the medial canthus (middle corner of the eye).
A type of refractive error related abnormal curvatures on the anterior or posterior surface of the cornea.
A Number 0 Tessier cleft is a true median cleft lip with a broad columella and bifid nasal tip. The alveolar cleft is between the central incisors. The nasal septum may be thickened, duplicated, or absent. The nasal bridge is usually broad with associated orbital hypertelorism. The midline soft tissue anomaly may range from a mild broadening of the philtrum or there may be a true median cleft lip. The columella and nasal tip are typically bifid and broadened with a midline depression. The alae nasi are intact but laterally displaced. The nose appears shortened in the vertical dimension.
A type of facial cleftlocated near to but not directly on the midline of the face.
As seen in a typical cleft lip, a cleft of the lip is found in the region of the cupid's bow. The nostril is cleft through the alar dome and extends above onto the nasal dorsum. It passes medial to a normal, but dys- topic, medial canthus. There is an alveolar cleft between the central and lateral incisors that extends above through the pyriform margin lateral to the anterior nasal spine; the nasal septum is not involved. The bony cleft extends through the nasal bone or between the junction of the nasal bone and frontal process of the maxilla. Above the cleft lip, the clefting of the alar dome is associated with deviation to the opposite side of the shortened and broadened columella and nasal tip. Extension of the soft tissue cleft onto the nasal dorsum can be manifest as a series of vertical soft tissue furrows and ridges. Vertical inner canthal dysto- pia and severe telecanthus mark the superior aspect of the Number 1 facial cleft. A cranial soft tissue extension characterized by a tongue-like projection of the frontal hairline delineates the number 13 cleft. Skeletal clefting of the maxilla may extend posteriorly to form a complete cleft of the hard and soft palate. The maxilla is hypoplastic in all three dimensions. There is a keel-shaped alveolus and anterior open bite. Normal septation is preserved between the nasal cavity and the hypoplastic maxillary antrum on the affected side. Distortion of the nasal skeleton produces gross flattening of the nasal dorsum. There is asymmetry of the pterygoid plates, of the greater and lesser wings of the sphenoid, and of the floor of the anterior cranial fossa. The distortion of the cranial base may result in a mild plagiocephaly.
As is typically seen in isolated cleft cases, a cleft of the lip is present. There is hypoplasia, but not true notching of the ala nasi with flattening of the lateral part of the nose. The nasal root is broadened, with lateral displacement of the inner canthus. The palpebral fissure and lacrimal drainage system are not disturbed. The alveolar cleft is through the lateral incisor area and extends to the pyriform aperture. There is normal septation between the nasal cavity and maxillary sinus. Notching at the junction between the nasal bone is present, as is a broad, flat frontal process of the maxilla. Transverse ethmoid enlargement produces orbital hypertelorism. Above the cleft of the lip and palate is a true broad cleft of the nostril that is medial to the intact, but laterally displaced, tail of the alar cartilage. A shallow soft tissue groove extends superiorly to the asymmetrically widened nasal root. The lacrimal system, palpebral fissures, and eyebrows remain intact. The alveolar cleft extends posteriorly as a complete unilateral cleft of the hard and soft palate. The nasal septum is intact but deviated to the opposite side. The nasal cavity remains separated from the normally pneumatized, although hypoplastic, maxilla on the cleft side. Above the nasomaxillary notching, the ethmoid sinus is less well developed, and there is no pneumatization of the frontal sinus on this side. Anterior rotation of the greater and lesser wings of the sphenoid occurs on the cleft side in relation to the narrower orbit and smaller ethmoid sinus. There is mild asymmetry of the anterior cranial fossa, which is narrower on the cleft side. The cranium is brachycephalic with marked occipital flattening.
A facial cleft characterized by involvment of the orbit.
As in the Number 1 and Number 2 clefts, this cleft extends through the lip in the region of the typical cleft lip; however, it does not extend through the base. The cleft continues superiorly to involve the inner canthus and lower eyelid medial to the inferior lacrimal punctum, thereby disrupting the nasolacrimal system. Microphthalmia may be present. The alveolar cleft is between the lateral incisor and the canine. Absent septation between the nasal cavity and maxillary antrum, together with the distortion of the frontal process of the maxilla and lacrimal fossa, produces direct communication between the orbit, maxillary sinus, and nose. There is hypoplasia of the soft tissue margins of the cleft in the vertical dimension. This produces extreme soft tissue deficiency between the alar base and the cleft of the medial aspect of the lower eyelid. The inferior lacrimal punctum is evident at the lateral margin of the lower eyelid cleft. The lacrimal drainage system ends as an opening directly onto the cheek without communication into the nasal cavity. The globe is normal in size, but it is displaced inferiorly and laterally. The nasal septum shows the characteristic distortion seen in typical cleft lip and palate. There is absence of septation between the nasal cavity on the cleft side and the maxilla. The maxilla is hypoplastic in three dimensions, with a marked reduction in pneumatization. Superior extension of the skeletal clefting into the medial portion of the orbital floor and into the inferior orbital rim in the region of the frontal process of the maxilla allows direct communication between the orbit above and the nasomaxillary region below. There is mild narrowing of the ethmoid sinus and of the body of the sphenoid on the cleft side. The pterygoid process appears anatomically normal, but less displaced from the midline compared with that of the noncleft side. Both the orbit and the floor of the anterior cranial fossa are inferiorly displaced.
The cleft lip is midway between the philtral ridge and the commissure of the mouth. The cleft is lateral to the normally shaped and placed nasal ala and passes onto the cheek. The cleft extends through the lower eyelid lateral to the punctum. The lacrimal system and inner canthus are normal. Microphthalmia may be present. The alveolar cleft passes between the lateral incisor and canine, as in the Number 3 cleft. The cleft passes around the pyriform aperture and continues through the portion of the maxillary sinus medial to the infraorbital foramen. The cleft terminates at the medial end of the inferior orbital rim. There is severe vertical soft tissue deficiency in a Number 4 cleft, with the medial margins of the cleft lip extending directly into the medially placed cleft of the lower eyelid. Within the medial segment of the right-sided cleft lip, muscle elements are apparently absent. Muscle bunching is noted in the ipsilateral lateral lip segment, as is seen in a typical unilateral cleft lip. The anatomically normal nasal ala is superiorly displaced in association with a severe deficiency in the overall nasal length. Marked dystopia of the right globe results in its inferior displacement into the medially deficient orbital floor and inferior rim. Both globes are otherwise normal. The complete palatal cleft passes through the maxilla medial to the infraorbital foramen and extends to the medial portion of the inferior orbital rim without evidence of an intact maxillary sinus. Bony septation persists medially, thereby separating the nasal cavity from the orbit, maxillary sinus, and mouth, which are contiguous. Marked midfacial hypoplasia is present. The cleft is manifest as asymmetry of the body of the sphenoid; it is smaller on the right, with asymmetric placement of the pterygoid plates relative to the midline. The orbital floor cleft has no communication with the inferior orbital fissure. The cleft does not extend to the skull base, but there is marked facial asymmetry associated with plagiocephaly.
The cleft of the lip is just medial to the oral commissure and extends across the cheek as a furrow. It ends as a cleft at the junction of the middle and lateral third of the lower eyelid. Microphthalmia is frequently present. The alveolar cleft is through the premolar region and extends superiorly through the orbit at the inferolateral part of the rim and floor. There is a vertical soft tissue deficiency between the lateral portion of the lip and the lower eyelid cleft. The left side of the nose shows vertical shortening, and the left alar base is displaced superiorly. Facial asymmetry secondary to the skeletal abnormality is reflected by a vertical orbital dystopia. However, bothglobes are normal, and there is no abnormality of the upper eyelids, eyebrow, forehead, or frontal hairline. The skeletal clefts vary, ranging from a narrow skeletal furrow that traverses the anterior maxillary wall as on the rightto a broad cleft of the maxilla lateral to the infraorbital foramen and maxillary sinus. This latter cleft enters the inferolateral orbital rim and floor without posterior communication with the inferior orbital fissure on the left side. Medial collapse of the lateral maxillary segments is present bilaterally, with reduction in the transverse dimensions of the maxillary arch. Manifestations of the skeletal disturbance in the sphenoid include a shortening and thickening of the lateral orbital walls in the region of the greater wing and mild asymmetric placement of the pterygoid plates relative to the midline. The right-sided pterygoid plates are smaller and closer to the midline. There is minimal asymmetry of the cranial base and calvarium.
A facial cleft extending from the zygomatic arch to the eye. This zygomaticomaxillary cleft is similar to that typically found in Treacher Collins syndrome. The overlying tissue shows a vertical sclerodermic furrow radiating from the labial commissure or the angle of the mandible across the cheek to a coloboma of the lower eyelid between the middle and lateral one-third. Microphthalmia is not observed. The skeletal cleft is between the maxilla and zygoma; it passes through the inferolateral orbital rim to enter the inferior orbital fissure. No alveolar cleft is present. The zygomatic arch is intact. The soft tissue furrow, which is more apparent on the right, radiates from the oral commissure toward the lateral two-thirds of the lower eyelid. The antimongoloid obliquity of the palpebral fissures is associated with laterally placed lower eyelid clefts and some ectropion. Aleft-sided anophthalmia is accompanied by adjacent soft tissue hypoplasia and is reflected in a short palpebral fissure, enophthalmos, and minor ptosis of the eyebrow. No abnormality is present in the alveolar arch except for some tilting of the occlusal plane secondary to hypoplasia of the left side of the maxilla. There is a vertical bony groove in the region of the zygomaticomaxillary suture that ends in the inferolateral portion of a small bony orbit. More laterally, the remainder of the zygomatic body and arch is normal in both shape and dimension. The lateral orbital floor is downslanting but intact, and it lacks direct communication with the temporal or infratemporal fossae. The hypoplasia of the left side of the maxilla and orbit is associated with a reduction in the transverse and anteroposterior dimensions of the anterior cranial fossa; mild asymmetry of the middle cranial fossa and calvarium is present. No significant asymmetry of size, shape, or position is present in the sphenoid.
The temporozygomatic Number 7 cleft is found in both Treacher Collins syndrome and hemifacial microsomia. Soft tissue manifestations include macrostomia, malformations of the external and middle ear, temporalis muscle, variable involvement of the seventh cranial nerve (in hemifacial microsomia), and abnormalities of the preauricular hair in Treacher Collins syndrome. The skeletal cleft is through the pterygomaxillary junction, and vertical maxillary hypoplasia is present. In addition, abnormality of the mandibular ramus, coronoid, and condyle and absence of the zygomatic arch are typically present. A soft tissue furrow extends from the macrostomia laterally and superiorly across the cheek toward the preauricular hairline. The lower eyelids are intact. The anatomy of the external ear is normal, and there are no preauricular tags. Bony clefting is through the pterygomaxillary junction with hypoplasia of the alveolar process in the molar region, thereby producing a posterior open bite. The maxilla is hypoplastic, although the maxillary sinuses are symmetrically pneumatized. The hypoplastic zygomatic body arches upward, but then it takes a downward course and is severely malformed and displaced. The zygoma is continuous posteriorly with an apparently normal zygomatic process of the temporal bone. The mandibular condyle and coronoid process are hypoplastic and asymmetric. There is no antegonial notching of the mandible. Marked cranial base asymmetry, with tilting and asymmetric positioning of the temporomandibular articulations, is present. The anatomy of the sphenoid is abnormal, especially on the right where there is no recognizable medial or lateral pterygoid plate.
The frontozygomatic or Number 8 cleft is found in both Treacher Collins syndrome and the Goldenhar variant of hemifacial microsomia. Skeletal defects are more prominent in Treacher Collins syndrome, whereas the soft tissue clefting is more typical in cases of ''Goldenhar syndrome''. Soft tissue clefting presents as a dermatocele, a true lateral eyelid coloboma with absence of the outer canthus, and anomalies of the globe itself, especially epibulbar cysts in patients with Goldenhar syndrome. The frontozygomatic bony cleft produces absence of the lateral orbital rim; this border now is formed by the hypoplastic greater wing of the sphenoid. The absence of bony support for the outer canthus produces lateral canthal dystopia and the characteristic antimongoloid slant of the palpebral fissures. Secondary to the bony deficiency in the lateral orbital wall and floor, there is soft tissue continuity between the orbit, temporal fossa, and infratemporal region. Preauricular hairline indicators delineate the Number 8 cleft as the first of the northbound clefts. Complete absence of the bony lateral orbital wall and rim constitute the skeletal element of the Number 8 cleft. The lateral border of the orbit is formed by the greater wing of the sphenoid from which small spicules of bone, which represent the rudimentary zygoma, may be found in Treacher Collins syndrome. The symmetry of the facial anomalies is reflected in the apparently normal symmetric anterior and middle cranial fossae.
This is an upper lateral orbital cleft. The soft tissue deformity is in the lateral one-third of the upper eyelid, and the bony cleft is through the superolateral orbital angle. Microphthalmia is present. The superolateral bony deficiency of the orbits allows a lateral displacement of the globes. The lateral one-third of the upper eyelid and the outer canthus are distorted, thus preventing apposition to the globe. The upper eyelid does not have a true cleft. A soft tissue furrow radiates superiorly and posterisphenoid is symmetric and normal. Mild cranial base asymmetry is reflected in the pterygoid plates. The left pair is more laterally displaced from the midline. Skull vault plagiocephaly is evident with an apparent reduction in the anteroposterior dimension of the anterior cranial fossa.
In a Number 10 Tessier cleft there is an upper central orbital cleft with a cleft of the middle one-third of the upper eyelid, which often results in total ablepharia. The eyebrow is disrupted, being virtually absent medially, whereas the lateral portion angles upward toward the frontal hairline. There may be ocular anomalies, including colobomata of the iris. The skeletal cleft is through the midportion of the supraorbital rim, the adjacent frontal bone, and the orbital roof lateral to the supraorbital nerve. A frontal encephalocele frequently occupies the frontal bony cleft. The palpebral fissure is grossly elongated with an amblyopic eye displaced inferiorly and laterally. There is also a divergent squint of the right eye. The eyebrow is deficient medially and becomes thinned out laterally , where it is contiguous with a broad downward and forward projection of the frontotemporal hairline (this may be seen in both the Number 9 and 10 clefts.) A broad frontal encephalocele bulges forward from the middle one-third of the right forehead, supraorbital ridge, and orbital roof. The bony cleft, through which the frontal encephalocele presents, involves the anterior half of the orbital roof, the supraorbital rim, and two-thirds of the vertical height of the frontal bone lateral to the supraorbital nerve. The bony orbit is inferiorly displaced and widened with the lateral orbital wall shortened and laterally deviated. Similar distortion of the anterior cranial fossa is evident, being broader and more flattened on the affected side. The calvarium above the level of the cleft and the cranial base below is symmetric.
An upper medial orbital cleft produces a cleft of the medial one-third of the upper eyelid that extends through the eyebrow into the frontal hairline. The skeletal element of the cleft in the region of the frontal process of the maxilla may either pass lateral to the ethmoid, through the supraorbital rim, or it may pass through the ethmoidal labyrinth to produce orbital hypertelorism. This cleft usually accompanies the Number 3 cleft. The soft tissue features include a cleft of the medial portion of the upper eyelid, an irregularity in hair orientation at the medial end of the eyebrow, and a long tongue-like projection of the frontal hairline onto the forehead. There is a mild flattening of the frontal process of the maxilla and extensive pneumatization of both the ethmoidal and frontal sinuses, both of which are more prominent on the cleft side. No bony clefting of the supraorbital rim or frontal bone is evident. The cranial base and sphenoid architecture, including the pterygoid processes, are symmetric and normal.
There is a soft tissue cleft medial to the inner canthus with a cleft of the root of the eyebrow. The frontal process of the maxilla is flat and broadened, and the ethmoid labyrinth is increased in tranverse dimension, thereby producing orbital hypertelorism. The cribriform plate is of normal width. The frontal sinus is enlarged. Even though the frontal bone is flattened, bony clefts with encephalocele have not been observed. There is a lateral displacement of the inner canthus with a mild thinning, aplasia, or irregularity of the medial end of the eyebrow. There are no eyelid clefts. The soft tissue contour of the forehead is normal, with only a short downward prolongation of the paramedian frontal hairline to mark the superior extent of the soft tissue cleft. Flattening of the frontal process of the maxilla, an increase in the transverse dimension of the ethmoid sinus, and a laterally convex bowing of the medial orbital wall produce orbital hypertelorism. Superiorly there is a minor flattening of the frontal bone medially, and the nasofrontal angle is somewhat obtuse. The extensive pneumatization of the sinuses on the cleft side extends backward through the frontal and ethmoid sinuses and into the sphenoid sinus. The anatomy of the sphenoid, including the pterygoid processes, is otherwise normal. The anterior and middle cranial fossae floors are both broadened on the cleft side with minor widening of the cribriform plate.
There is a paramedian frontal encephalocele and a soft tissue cleft that passes medial to an intact eyebrow. The frontal bone shows a paramedian bony cleft with an associated encephalocele. The olfactory groove, cribriform plate, and ethmoid sinus are all increased in transverse diameter, resulting in hypertelorism. The cleft extends medially to the undisturbed eyebrow to end in a short paramedian frontal widow's peak. The bony cleft begins in the region of the nasal bone and extends superiorly through the full height of the frontal bone. Posteriorly, the cleft extends through the cribriform plate and ethmoid sinus as far as the lesser wing and body of the sphenoid. The pterygoid processes are anatomically normal, but they are displaced laterally from the midline on the cleft side. There is orbital hypertelorism below and asymmetry of the floor of the anterior cranial fossa above.
This midline cranial cleft usually occurs with a midline facial cleft that completes a median craniofacial dysraphia. A broad nasal root and bifid nose are associated with orbital hypertelorism and a median frontal encephalocele. The frontal bone abnormality varies from a minor flattening to a large midline defect. There is an increased distance between the olfactory grooves. The crista galli is widened, duplicated, or in some cases absent. Marked inferior prolapse of the enlarged ethmoid bone occurs with orbital hypertelorism. The severe orbital hypertelorism is associated with a broad flattening of the glabella and extreme lateral displacement of the inner canthi. The periorbita, including the eyelids and eyebrows, are otherwise normal. A long midline projection of the frontal hairline marks the superior extent of the soft tissue features of this midline cranial cleft. The median frontal defect delineates the region through which the frontal encephalocele herniates. The lateral segments of the frontal bone sweep upward from the region of the intact glabella and are flattened laterally. No pneumatization of the frontal sinus is evident. The crista galli and the perpendicular plate of the ethmoid are bifid. Just as the ethmoid, including the cribriform plate, is widened and caudally displaced, the sphenoid sinus is broadened and extensively, but symmetrically pneumatized. The lateral rotation of the greater and lesser wings of the sphenoid results in a relative shortening of the anteroposterior dimension of the middle cranial fossa. The floor of the anterior cranial fossa is upslanting from its medial aspect to its lateral aspect, with a harlequin appearance on the coronal scan.
A lower midline facial cleft, also known as the median mandibular cleft. It is a rare anomaly, which may be limited to a defect in the soft tissue of the lower lip. However, in the more severe form, it may extend into the bony mandibular symphysis.
A conspicuously unhappy disposition characterized by negative assumptions, self-defeating talk, fear of failure, and negative ruminations about past events.
Frequent thinking about or preoccupation with killing onself.
Eye strain, i.e., a feeling of fatigue or discomfort of the eyes related to 'overuse' of the eyes in activities such as reading or working at the computer and often accompanied by lacrimation or headache.
An abnormally large Eustachian valve (postnatally). The Eustachian valve is also known as the valve of the inferior vena cava, and is an embryologic remnant of the valve of the inferior vena cava.
Situs inversus of thoracic and abdominal viscera with the heart remaining normally situated on the left; usually associated with congenital cardiac abnormalities such as transposition of the great vessels and/or spleen defects including asplenia or polysplenia.
An anomaly of the PR interval, which is the portion of the ECG from the end of the P wave to the beginning of the QRS complex. A normal PR interval in adults is from 0.12-0.2 seconds.
A reduction in voltage of the PR segment below baseline.
Any anomaly of the P wave of the EKG, which results from atrial depolarization. The P wave occurs when the sinoatrial node creates an action potential that depolarizes the atria.
An anomaly of the PR segment, which begins at the endpoint of the P wave and ends at the onset of the QRS complex. The PR segment is normally flat and isoelectric.
An increase in voltage of the PR segment below baseline.
V-shaped cut (notch) in the middle of the P wave.
A broad (120 ms or longer in duration) and bifid P-wave in EKG lead II.
P wave below insteadof above the baseline. P-wave inversion in the inferior leads may indicate a non-sinus origin of the P waves.
The presence of tall, peaked P waves in EKG lead II.
An anomaly in the system of mucociliary transport, which functions to transport the mucous layer lining the respiratory epithelium by ciliary \nbeating.
An abnormally increased amount of time required to clear mucus (and substances contained in the mucus) from the nasal mucosa. The nasal mucociliary clearance (NMC) system functions to transport the mucous layer lining the nasal epithelium towards the naso pharynx by ciliary beating in a metachronous fashion at a frequency of 7-16 Hz. NMC depends upon two principal components: physicochemical qualities and quantities of mucus and the properties of cilia that propel it. NMC is considered to be representative of pulmonary clearance. normal NMC time is determined to be up to 20 minutes. Duration of 30 minutes is considered as the cutoff point that discriminates normal subjects from subjects with impaired NMC. NMC can be measured by determination of the transport time of markers that are placed on the nasal mucosa including saccharine, radioactive markers, and dyes.
A developmental defect characterized by the lack of formation of the carotid canal, which normally is a circular aperture in the temporal bone of the skull through which the internal carotid artery and the carotid plexus of nerves traverse.
Any anomaly of the pigmentation of the fundus, the posterior part of the eye including the retina and optic nerve.
Fluffy white patch on the retina, representing localized areas of dense white swelling of the retinal nerve fibre layer. They often have a zigzag internal structure, a feathered edge but an otherwise well-delineated form and an approximately 1 mm dimension; they project slightly into the vitreous and sometimes deflect retinal vessels.
Weakness in the supporting structures of the pelvic floor allowing the pelvic viscera to descend or one or more of the pelvic organs drop from their normal position.
Sharply demarcated area of partial or complete depigmentation of the fundus reflecting atrophy of the retinal pigment epithelium with associated retinal photoreceptor loss. The margins of the de-pigmented area are usually scalloped and the large choroidal vessels are visible through the atrophic retinal pigment epithelium.
A type of intraretinal hemorrhage that is located in the superficial retina between the inner limiting membrane and the retinal nerve fiber layer.
Absence of a region of the retina, retinal pigment epithelium, and choroid at the lower part of the fundus.
A notch or cleft of the lower part of the retina.
Presence of pus (appears as a white fluid) producing a fluid level in the inferior part of the anterior chamber.
An abnormal appearance of the beam of light traveling through the anterior chamber of the eye in a slit lamp examination. The flare is produced by an increased concentration of proteins in the aqueous humor in the anterior chamber.
Moderate anterior chamber flare (iris and lens details clear).
Marked anterior chamber flare (iris and lens details hazy).
Intense anterior chamber flare (fibrin/plastic aqueous).
An ocular motility defect where the affected eye(s) does not elevate in adduction but has full depression in adduction. It can be congenital or acquired from injury to or defect of the superior oblique tendon or trochlea and has a positive forced duction test result.
Drooping of the upper eyebrow below the superior orbital rim.
A moderate form of myopia with refractive error of between -3.00 and -6.00 diopters.
Absence of the normal opening of a coronary ostium. There are normally two coronary ostia, which are site of origin of the main left or right main coronary artery and are located in the ascending aorta just above the aortic valve.
Pathological deposition of calcium salts in the globus pallidus.
Cardiac arrest that would have led to rapid and unexpected death had an intervention not taken place to prevent it.
Reduced ability to walk in a straight line while placing the feet heal to toe.
Any structural anomaly located between the pleura and the chest wall.
So-called honeycombs (variably sized cysts in a background of densely scarred tissue) located in the subpleural space.
Abnormal origin of the right subclavian artery from the descending aorta. The right subclavian artery normally arises from the brachiocephalic trunk, which divides into the right common carotid artery and right subclavian artery.
The loss of continuity between the left subclavian artery and the aorta, with persistent connection to the homolateral pulmonary artery through the patent (PDA) or nonpatent ductus arteriosus.
The left common carotid artery normally originates from the aortic arch. This term refers to an origin of this artery from the main pulmonary artery.
The left common carotid artery normally originates from the aortic arch. This term refers to an origin of this artery from the brachiocephalic artery.
The right common carotid artery normally originates from the brachiocephalic artery. This term refers to an origin of this artery directly from the aorta.
Absence of the normal opening of the coronary ostium from which the right main coronary artery originates.
The left anterior descending artery (LAD) branches off from the pulmonary artery.
The left main coronary artery (LMCA) is absent and the left anterior descending (LAD) and left circumflex (LCX) arteries arise from separate but adjacent ostia in the left sinus of Valsava.
Any structural anomaly of the radial artery.
An eccentric abnormal localized widening (dilatation) of the ascending tubular aorta that involves only a portion of the circumference of the vessel wall.
A concentric abnormal localized widening (dilatation) of the abdominal aorta that involves the full circumference of the vessel wall
An eccentric abnormal localized widening (dilatation) of the abdominal aorta that involves only a portion of the circumference of the vessel wall.
A concentric abnormal localized widening (dilatation) of the aortic arch that involves the full circumference of the vessel wall.
An eccentric abnormal localized widening (dilatation) of the aortic arch that involves only a portion of the circumference of the vessel wall.
A focal defect in the elastic lamina of the aortic wall that leads to localized medial disruption and potential rupture.
Tearing of the aortic wall generally associated with profuse internal bleeding.
Any functional defect of the mitral or tricuspid valve.
Any functional defect of the tricuspid valve.
Any functional abnormality of a cardiac valve.
Any functional anomaly of the pumonary valve.
The presence of an aortic valve with four instead of the normal three cusps (flaps).
Systolic anterior motion of the mitral valve (SAM) is a paradoxical motion of the anterior, and occasionally posterior, mitral valve leaflet towards the left ventricular outflow tract (LVOT) during systole.
Any abnormal noise generated by the beating heart.
The third heart sound (S3) is related to rapid filling in diastole. S3 can be a normal finding in children and adolescents but suggests heart failure in older patients.
Abnormally increased volume of the first heart sound.
Any anomaly of the second heart sound (S2), which is produced by aortic (A2) and pulmonic (P2) valve closure. The A2-P2 interval normally increases with inspiration and narrows with expiration.
Lack of variation in the splitting between the two components of the second heart sound with respiration. Normally, the aortic valve closure (A2) is followed by the pulmonic valve closure (P2) but the A2-P2 interval increases with inspiration and decreases with expiration.
Normally, the aortic valve closure (A2) is followed by the pulmonic valve closure (P2) but the A2-P2 interval increases with inspiration and decreases with expiration. With paradoxical splitting, there is a delay in the closure of the aortic valve, so that A2 can follow P2; the individual components can be appreciated at the end of expiration and the interval narrows with inspiration (which is the oposite of the normal pattern).
A heart murmur limited to systole, i.e., between the first and second heart sounds S1 and S2.
A systolic murmur that begins after S1 and ends before S2, typically with a crescendo-decrescendo pattern.
A murmur that occurs in the latter phase of systole.
A heart murmur that occurs during the entire systolic phase from S1 to S2.
A heart murmur that occurs during diastole, i.e., in the time between S2 and the subsequent S1.
A murmur that occurs in the middle of the diastolic phase.
A murmur that occurs in both systole and diastole.
Typical atrial flutter is an organised atrial tachycardia. It can also be defined as a macroreentrant tachycardia confined to the right atrium. This arrhythmia has a 200-260 ms cycle length, although it may fluctuate depending on patient's previous treatment or ablation, congenital heart disease, etc. Ventricular rate response will be limited by the atrioventricular node conductions, usually presenting a 2:1 or 3:1 response, during atrial flutter. Typical (counter clockwise) flutter is associated with the common flutter pattern: a regular continuous undulation with dominant negative deflections in inferior leads II, III and aVF, often described also as a saw tooth pattern, and flat atrial deflections in leads I and aVL. Atrial deflections in V1 can be positive, biphasic or negative.
A type of atrial flutter associated with rounded or bimodal positive deflections in inferior leads II, III and aVF, and a very characteristic bimodal negative wave in the shape of a W is seen in lead V1.
A type of atrioventricular reentrant tachycardia (AVRT) where the are the atrioventricular node is used for anterograde conduction and the accessory pathway for retrograde conduction.
A type of atrioventricular reentrant tachycardia (AVRT) where the are the accessory pathway is used for anterograde conduction and the atrioventricular node for retrograde conduction.
A ventricular tachycardia (VT) characterized by right bundle branch block (RBBB) and left axis deviation (LAD) on electrocardiogram (ECG).
A type of ventricular tachycardia that is characterized by uniform QRS complexes within each lead (i.e., each QRS is identical or nearly so).
A type of ventricular tachycardia that is characterized by variable QRS complexes within each lead (i.e., QRS complexes may be different from beat to beat).
A lesion associated with atherosclerosis, a multifactorial and multipart progressive disease manifested by the focal development within the arterial wall of lesions, that ranges from teh development of a fatty streak, plaque progression, and plaque disruption. Atherosclerotic lesions demonstrate consistent morphological characteristics, which indicate that each type may stabilize temporarily or permanently and that progression to the next type may require an additional stimulus.
Type I lesions represent the very initial changes and are recognized as an increase in the number of intimal macrophages and the appearance of macrophages filled with lipid droplets (foam cells).
Type II atherosclerotic lesions include the fatty streak lesion, the first grossly visible lesion, and are characterized by layers of macrophage foam cells and lipid droplets within intimal smooth muscle cells and minimal coarse-grained particles and heterogeneous droplets of extracellular lipid.
Type III (intermediate) atherosclerotic lesions are the morphological and chemical bridge between type II and advanced lesions. Type III lesions appear in some adaptive intimal thickenings (progression-prone locations) in young adults and are characterized by pools of extracellular lipid in addition to all the components of type II lesions.
Type V lesions are defined as lesions in which prominent new fibrous connective tissue has formed. When the new tissue is part of a lesion with a lipid core (type IV), this type of morphology may be referred to as fibroatheroma or type Va lesion. A type V lesion in which the lipid core and other parts of the lesion are calcified may be referred to as type Vb. A type V lesion in which a lipid core is absent and lipid in general is minimal may be referred to as type Vc. With these lesions, arteries are variously narrowed, generally more than with type IV. Importantly, as with type IV lesions, type V lesions may develop fissures, hematoma, and/or thrombus (type VI lesion), and for this reason too they are clinically relevant.
Type VI atherosclerotic lesions generally have the underlying morphology of type IV or V lesions, surface disruptions, hematoma, and thrombosis may be (although less often) superimposed on any other type of lesion and even on intima without an apparent lesion. Complicating features may arise because of individual differences in risk factors and tissue reactions. These may include differences in composition of the blood, the relative quantities and distributions in the components of the underlying lesion or intima, as well as modifications of shear and tensile forces to which the lesion or intima is exposed. Clinical imaging of lesions may be expected to contribute greatly to the understanding of type VI lesions and the associated clinical syndromes.
An atherosclerotic lesion located in the renal artery.
An abnormally elevated amount of alpha1-antitrypsin in the feces.
Dysplasia in the erythroid lineage, which presents with a variety of morphological changes in the bone marrow, including nuclear budding or irregular nuclear contour in erythroblasts. In peripheral blood.
The presence of micro-megakaryocytes, hypo-lobed, or non-lobed nuclei in megakaryocytes of all sizes and multiple, widely-separated nuclei.
An infection that is caused by a pathogen that would generally not be able to cause an infection in a host with a normal immune system. Such pathogens take advantage of the opportunity, so to speak, that is provided by a weakened immune system.
An unusually severe infection by cytomegalovirus.
An unusually severe Epstein Barr virus (EBV) infection.
An unusually severe adenovirus infection.
An unusually severe infection by a parainfluenza virus.
A viral infection that fails to be contained by the immune sytem and spreads throughout the body.
A dissemination viral infection caused by a live attenuated vaccine virus.
Failure to contain thebacillus Calmette-Guerin (BCG) following vaccination leading to spread of BCG to many sites in the body. The tuberculosis vaccine BCG contains live attenuated Mycobacterium bovis.
Failure to contain infection by a protozoan of the genus Cryptosporidium, leading to spread to many parts of the body.
A parasitic infection whereby the parasite invades (migrates through) tissues of the infected host.
The presence of inflammatory cells in the aqueous humor of the anterior chamber of the eye.
The presence of erythrocyte in the aqueous humor of the anterior chamber of the eye.
A compensatory head posture occurs when the head is deviated out of the normal primary straight head position in order to compensate for an ocular problem.
A tendency to hold the chin depressed (lowered) to compensate for a limitation of eye movement.
A tendency to turn the face to the right to compensate for a limitation of eye movement.
A tendency to turn the face to the left to compensate for a limitation of eye movement.
A tendency to tilt the head towards the right shoulder to compensate for a limitation of eye movement.
A tendency to tilt the head towards the left shoulder to compensate for a limitation of eye movement.
An abdominal aortic aneurysm that is not symmetric around its axis (not axisymmetric).
A form of divergent strabismus (exotropia) in which the eye turns outward at all distances and at all times.
A type of divergent strabismus (exotropia) in which an eye tends to turn outwards (i.e., the eye squints) mainly when looking at distant objects. The eyes tend to remain straight when they look at near objects. Distance exotropia may be constant or intermittant.
An intermittent exotropia where there is binocular single vision on distance fixation and exotropia at near (intermittent or constant).
A type of exotropia (divergent strabismus) in which binocular single vision alternates with large angle exotropia in rhythmic cycle.
A type of exotropia in which either eye may be used for fixation.
Exotropia in an individual who has previously had esotropia or esophoria.
Exotropia (intermittent or constant) on distance fixation with binocular single vision on near fixation under all testing conditions. The accommodative convergence/accommodation (AC:A) ratio is within normal limits.
Exotropia (intermittent or constant) worse for distance fixation in which the near angle of deviation increases (or near exophoria becomes exotropia) with: (1) prolonged disruption of fusion and/or (2) elimination of accommodation.
An intermittent esotropia where there is binocular single vision on distance fixation and esotropia at near even when the accommodation is relieved.
Convergent squint which follows loss or impairment of vision.
A small angle heterotropia (usually of 10 diopters or less) in which a form of binocular single vision occurs.
A form of latent strabismus (heterophoria) in which, on dissociation, the occluded eye deviates downwards.
A type of cyclotropia (torsion of one or both eye about the visual axis of the eyes) in which the upper poles of the globes are rotated inward (medially) to each other.
A type of cyclotropia (torsion of one or both eye about the visual axis of the eyes) in which the upper poles of the globes are rotated outward (laterally) to each other.
A form of hypermetropia with not more that +2.00 diopters.
A form of hypermetropia with more than +2.00 diopters but not more than +5.00 diopters.
A form of myopia related to an axial length above the norm and too long for the refractive power of the whole optical system of the eye.
Increased lacrimation owing to overproduction of tears.
A form of watery eye associated with overproduction of tears due to an increased parasympathetic drive to the secretory component of the lacrimal system (lacrimal gland); this could be due to pro-secretory drug use (e.g. pilocarpine) or autonomic disturbance.
A form of watery eye associated with overproduction of tears due to reflex tearing in response to a local irritant (e.g. trichiasis or foreign body), chronic ocular surface disease (e.g. blepharitis) or systemic disease (e.g. thyroid eye disease).
A form of watery eye associated with abnormal lid tone and/or lid position. The former is due to lid laxity (common involutional change in the elderly) or a weak orbicularis muscle (e.g. due to VII cranial nerve palsy). The latter is typically associated with ectropion causing punctal eversion.
An abnormal inversion of the eyelid towards the globe resulting from inferior retractor muscle dysfunction with tissue laxity and, possibly, overriding of the preseptal orbicularis muscle over the pretarsal orbicularis muscle.
Abnormal inversion (turning inward) of the eyelid towards the globe associated with scarring that vertically shortens the posterior lamella of the eyelid.
A type of entropion (abnormal inversion of the eyelid towards the globe) that is related to a mass effect of a lesion (e.g., a tumor) that pulls the eyelid margin away from the globe.
A functional anomaly of the inferior or superior oblique muscle.
A functional anomaly of the medial rectus muscle or lateral rectus muscle.
Reduced ocular movement by the inferior oblique muscle which improves on testing ductions, typically associated with neurogenic palsy.
Reduced movement by the inferior rectus muscle which improves on testing ductions, typically associated with neurogenic palsy.
Excessive action of the inferior rectus muscle caused by increased innervation typically as a consequence of palsy or limitation to the ipsilateral antagonist or contralateral synergist.
Decreased strength of the superior rectus muscle.
Excessive action of the superior rectus muscle caused by increased innervation typically as a consequence of palsy or limitation to the ipsilateral antagonist or contralateral synergist.
Mechanical limitation of the range of movement of the superior rectus muscle.
Reduced movement of the superior rectus muscle which improves on testing ductions, typically associated with neurogenic palsy.
A functional anomaly of the superior or inferior rectus muscle.
A functional anomaly of the lateral rectus muscle.
Decreased strength (ability to move) of the lateral rectus muscle.
Reduced movement of the lateral rectus muscle which improves on testing ductions, typically associated with neurogenic palsy.
Excessive action of the lateral rectus muscle caused by increased innervation typically as a consequence of palsy or limitation to the ipsilateral antagonist or contralateral synergist.
Decreased strength of the medial rectus muscle.
Excessive action of the medial rectus muscle caused by increased innervation typically as a consequence of palsy or limitation to the ipsilateral antagonist or contralateral synergist.
A functional anomaly of a vertical or horizontal rectus muscle.
Reduced movement of the medial rectus muscle which improves on testing ductions, typically associated with neurogenic palsy.
Mechanical limitation of the range of movement of the medial rectus muscle.
Mechanical limitation of the range of movement of the lateral rectus muscle.
A form of convergent strabismus (esotropia) in which the deviation is present under all conditions (ie at all distances and at all times).
A form of esotropia in which the angle of deviation is not affected by accommodative effort.
Constant esotropia occurring before 6 months of age. It is typically associated with a large angle of deviation, alternating fixation (therefore low risk of amblyopia) and poor potential for binocular single vision. Other features that might be present in individuals with infantile (constant) esotropia include latent nystagmus or manifest latent nystagmus, dissociated vertical divergence, cyclotropia, abnormal head posture, limited abduction.
An intermittent esotropia where binocular single vision is present on near fixation and an esotropia on distance fixation. Often associated with myopia and aging.
Convergent strabismus in which normal binocular single vision is alternating with large angle esotropia in rhythmic cycle.
Esotropia in which normal binocular single vision is present for all distances when the hypermetropic refractive error is corrected. Esotropia is present for near and distance on accommodation without correction.
A form of constant esotropia in which the angle of deviation is partially affected by accommodative effort. Typically there is esotropia at near and distance with hypermetropic correction and the angle of deviation increases without glasses.
An intermittent esotropia with binocular single vision present at distance fixation but esotropia on accommodation for near fixation. Usually associated with hypermetropia but patients can be emmetropic and rarely myopic. Associated with a high accommodative convergence/accommodation (AC/A) ratio.
Esotropia in a patient who has previously had exotropia or exophoria; may be constant or intermittent. and usually follows surgical overcorrection.
Fixation of an object in the area adjacent to the fovea.
Fixation of an object in a peripheral area of the retina.
A type of epicanthus in which a medial vertical fold is present between upper and lower lids.
A type of epicanthus in which a primarily upper lid fold is present.
Any structural anomaly of the posterior circulating artery (PCOM).
A widening (ballooning) localized in the wall of the posterior communicating artery.
A funnel-shaped symmetrical enlargement of the origin of the posterior communicating artery at its junction with the internal carotid artery.
An ocular deviation caused by a palsy to one or more of the extraocular muscles or nerves supplying them.
A form of manifest strabismus (heterotropia) in which the one eye is wheel rotated so that the upper end of its vertical axis is nasal (incyclotropia) or temporal (excyclotropia).
A form of latent strabismus (heterophoria) in which the occluded eye wheel-rotates on dissociation.
A type of cyclophoria (latent strabismus in which the occluded eye wheel-rotates on dissociation.) in which the upper poles of the globes are rotated inward (medially) to each other.
A type of cyclophoria (latent strabismus in which the occluded eye wheel-rotates on dissociation.) in which the upper poles of the globes are rotated outward (laterally) to each other.
A type of ascites in which there are large numbers of eosinophils in the ascitis fluid.
A type of microtropia with no manifest movement on cover test, the eccentric fixation point coinciding with the angle of ARC.
A type of microtropia in which the manifest movement is demonstrated on the cover-uncover test.
A developmental defect in which the coronary sinus fails to form.
Any structural anomaly of the portion of the aorta that arises from the base of the left ventricle and extends upward to the aortic arch and from which the coronary arteries arise.
An abnormality in voluntary or involuntary eyelid movements or their control.
Transient eyelid retraction during refixation from down to straight ahead.
Astigmatism in which the refractive power of the vertical meridian is the greatest.
Refractive error in which the vertical meridian is relatively hypermetropic and the horizontal meridian is relatively myopic (or ocular astigmatism in which the refractive power of the horizontal meridian is the greatest).
Astigmatism with more plus power on the horizontal meridian.
A type of astigmatism in which an unequal curvature of the cornea and some cases additionally of the lens causes one meridian of the eye to be hyperopic (farsighted) and a second meridian that is perpendicular to the first to be myopic (nearsighted).
A type of astigmatism related to an irregular shape of the lens.
A type of astigmatism in which the principle meridians are not 90 degrees apart and which is associated with loss of vision.
An increased concentration of leptin in the blood.
A decrease below the normal concentration of glycerol in the blood.
Any deviation from the normal concentration of glycerol in the blood.
Increased circulating level of apolipoprotein B, which is the main apolipoprotein of chylomicrons and low density lipoproteins. It occurs in plasma as two main isoforms, apoB-48 and apoB-100.
Reduced criculating level of apolipoprotein AI, which is the major protein component of high density lipoprotein (HDL) in plasma. Defects in this gene are associated with HDL deficiencies, including Tangier disease.
An increased concentration in blood of apolipoprotein A-II, a major component of HDL particles, associated with triglyceride and glucose metabolism.
Any functional anomaly of the vocal cord.
A subtype of fundus hemorrhage occuring within the neurosensory retina. Intraretinal haemorrhages may be 'dot' or' blot' shaped or flame shaped depending upon their depth within the retina.
An anomaly of the number of basophils per volume in the blood circulation.
An abnormally increased count of basophils per volume in the blood circulation.
An abnormally reduced count of basophils per volume in the blood circulation.
Shortening of the fourth and fifth metacarpals when the fist is clenched.
Presence of conjugated bilirubin in the urine.
An excess of eosinophilic cells in colonic tissue, i.e., eosinophilic infiltration in the colon.
Repetition of one's own words or phrases.
A functional anomaly of the mouth (which is also known as the oral cavity).
Any structural anomaly of the mouth, which is also known as the oral cavity.
An abnormally decreased concentration of parathyroid hormone.
A deviation from normal of the waist to hip ratio, defined as the waist measurement divided by hip measurement.
Increased waist-to-hip ratio (WHR) is a measurement above the average for the dimensionless ratio of the circumference of the waist to that of the hips. WHR is calculated as waist measurement divided by hip measurement.
Decreased waist-to-hip ratio (WHR) is a measurement below the average for the dimensionless ratio of the circumference of the waist to that of the hips. WHR is calculated as waist measurement divided by hip measurement.
Altered level of the enzyme that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate.
Abnormally increased level of the enzyme that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate.
Abnormally decreased level of the enzyme that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate via transfer of the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate.
Freezing of gait is defined as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk.
Any anomaly of a reflex, i.e., of an automatic response mediated by the nervous system (a reflex does not need the intervention of conscious thought to occur).
Lack of contraction of abdominal muscles in the quadrant of the abdomen that is stimulated by scraping the skin tangential to or toward the umbilicus.
An anomaly of a reflex that is elicited as a motor response to scraping of the skin. They are generally graded as present or absent. They differ from tendon reflexes in that the sensory signal must ascend the spinal cord to reach the brain and then descend the spinal cord to reach the motor neurons.
Lack of response to scratching of the skin of the medial thigh, which inmales normally elicits a brisk, short eveletion of the ipsilateral testis, a phenomenon that is referred to as the cremaster reflex.
A pinguecula is a yellowish to brown protruding lesion in the conjunctiva that is easily seen on the nasal and temporal sides of the cornea.
An increasedreduced concentration of zinc in the blood.
Overshoot of downward saccadic eye movements.
Saccadic undershoot of upward saccadic eye movements, i.e., an upward saccadic eye movement that has less than the magnitude that would be required to gain fixation of the object.
Small ectopic arteries or arterial branches that connect the aorta, aortic branches and/or subclavian artery regions directly to the lung parenchyma, usually seen in conjunction with pulmonary atresia, ventricular septal defect (VSD) and/or closed ductus arteriosus.
An abnormal level of catalysis of the reaction: 2 superoxide + 2 H+ = O2 + hydrogen peroxide.
Increased catalysis of the reaction: 2 superoxide + 2 H+ = O2 + hydrogen peroxide.
Decreased catalysis of the reaction: 2 superoxide + 2 H+ = O2 + hydrogen peroxide.
Presence of a chemical substance found within an individual that is not naturally produced or expected to be present in human tissues or bodily fluids.
Detection of methadone or its metabolite 2-ethylidene-1,5-dimethyl-3,3- diphenylpyrrolidine (EDDP) in urine.
Dilation of the lymphatic vessels, the basic process that may result in the formation of a lymphangioma.
Any deviation from the normal sexual drive or desire for sexual activity.
Reduced ability to walk (ambulate) in a backwards direction.
An abnormality of gait that can be observed in individuals with dystonic posture in which the individual walks with an extended trunk and flexed arms, while strutting on the toes without the heels touching the floor.
A reversal of sleeping habits with a tendency to sleep during the day and to be awake at night.
Any deviation from the normal ratio of the volume of red blood cells to the total volume of blood.
A reduction below the normal ratio of the volume of red blood cells to the total volume of blood.
An abnormal gait characterized by toe walking, stiff legs, and skipping. The gait pattern has some resemblance to cock-walk gait, but in affected individuals are able to\nimprove their dystonic gait by walking backward.
Reduced or inadequate esophageal peristalsis, with resultant slow passage of contents through the esophagus.
Longitudinal grooves in the surface of the esophagus arranged in a longitudinal fashion (from top to bottom of the esophagus).
Any abnormality in the variability of the time interval between successive heartbeats.
Reduced variation of beat-to-beat intervals of the heart that occurs in conjunction with the respiratory cycle.
Increased variation of beat-to-beat intervals of the heart that occurs in conjunction with the respiratory cycle.
The presence of an infectious agent in the blood circulation.
Presence of viable bacteria in the blood.
Clasp-knife phenomonen refers to increased muscle tone while bending or stretching a limb, whereby there is a sudden relaxtion (decrease in resistance) as the muscle continues to be streched. This phenomenon has been likened to opening a clasp knife.
Increased passive stiffness or tightness of the neck musculature.
Difficulty reaching to visually guided goals in peripheral vision, with the deficit leaves voluntary eye movements largely unaffected.
Dislocation of a given joint repeated times.
An elevated concentration of phosphohydroxylysine in the urine.
Any functional anomaly of Langerhans cells, which are dendritic cells in the epidermis and some other locations. Langerhans cells play roles iin immune surveillance and homeostasis.
Birbeck granules (BG) are cytoplasmic organelles that are only found in Langerhans cells (LC). The function of BG is still not completely understood, although most studies point toward an active role in receptor-mediated endocytosis and participation in the antigen-processing/presenting function of LC. This feature refers to the absence of BG in LC, a feature that can be documented by means of electron microscopy.
A tendency towards rising very early in the morning and going to bed early in the evening.
A tendency towards rising very late in the morning and going to bed late at night.
Any deviation from the normal concentration of hepcidin in the blood circulation.
An abnormally reduced concentration of hepcidin in the blood circulation.
An abnormally increased concentration of hepcidin in the blood circulation.
Small hands and feet in proportion to the rest of the body.
Any functional abnormality of the eyelid.
Abnormally lax eyelid associated with tissue relaxation; it can be demonstrated by the eyelid distraction test and/or the eyelid snap test.
A form of watery eye associated with obstruction of the nasolacrimal system. This may arise at the level of the punctum, the canaliculi, the sac or the nasolacrimal duct.
A congenital abnormality of the cerebral hemisphere chacterized by lack of gyrations (convolutions) of the cerebral cortex.
An elevated concentration of proinsulin (the prohormone precursor to insulin) to mature insulin in the circulation.
A deviation from normal concentration of glucose content in the cerebrospinal fluid.
Abnormally high glucose concentration in the cerebrospinal fluid.
Any deviation from the normal concentration of low-density lipoprotein cholesterol in the blood circulation.
Any deviation from the normal circulating concentration of chylomicrons.
Any deviation from the normal concentration of high-density lipoprotein cholesterol (HDL) in the blood.
Any deviation from the normal concentration of very-low-density lipoprotein cholesterol in the blood.
An elevated concentration of urobilinogen in the urine.
Abnormal reduction in the count of eosinophils in the blood per volume.
Increased amount of stacking of erythrocytes into long chains. Rouleaux (singular: rouleau) is derived from a French word that can refer to a stack of coins put into a cylindircal paper roll. Rouleaux formation is observed with increased serum proteins, particularly fibrinogen and globulins, and represents the cause of increased erythrocte sedimentation rate because rouleaux sediment more readily than isolated red blood cells.
Any deviation from the activity of coagulation factor V.
Any deviation from the normal circulating concentration of mast cell beta-tryptase concentration.
An abnormally elevated circulating concentration of mast cell beta-tryptase concentration.
An abnormally reduced circulating concentration of mast cell beta-tryptase concentration.
Any deviation from the normal circulating concentration of selenium.
Any deviation from the normal total hemolytic complement activity in the circulation.
An abnormally elevated total hemolytic complement activity in the circulation.
An abnormally reduced total hemolytic complement activity in the circulation.
Abnormally small sized handwriting defined formally as an impairment of a fine motor skill manifesting mainly as a progressive or stable reduction in amplitude during a writing task.
A uterus that has a single horn, with a banana-like shape that may or may not have a secondary rudimentary uterine horn.
A functional abnormality affecting one or more of the cranial nerves, which emerge directly from the brain stem.
Decreased or absent sensation in the distribution of the trigeminal nerve, which provides tactile, proprioceptive, and nociceptive sensation in the area of the face and mouth.
Rhombencephalosynapsis is a rare brain malformation defined by midline fusion of the cerebellar hemispheres with partial or complete loss of the intervening vermis.
On open sore on the surface of the skin of a finger or toe.
A benign or malignant neoplasm that arises from the ovary and is composed of granulosa cells, Sertoli cells, Leydig cells, theca cells, and fibroblasts.
Juvenile granulosa cell ovarian tumor (JGCOT) is a rare sex cord stromal tumor, occuring most frequently in premenarchal girls or young women. In contrast to adult granulosa cell tumor, JGCOT has a high mitotic index and more aggressive tumor growth. Microscopically it is seen as diffuse and regularly distributed neoplastic cells with a wide cytoplasm and pleomorphic hyperchromatic nucleus. Follicle formation, in various sizes and shapes, is important in JGCOT. Call-Exner bodies are infrequently seen in JGCOT in contrast to the adult type.
An aggressive granulosa cell tumor that arises from the ovary.
The renal arteries carry blood from the aorta to the kidney; normally one renal artery is present on each side of the body. Renal artery duplication refers to the presence of two rather than one renal artery on a given side of the body.
Accumulation of blood in the vagina usually due to vaginal obstruction.
The presence of linear erythematous palpable cords, often on the lateral trunk.
A halo or spoke-wheel arrangement of cells surrounding a central core or hub. The central hub may consist of an empty-appearing lumen or a space filled with cytoplasmic processes. The cytoplasm of each of the cells in the rosette is often wedge-shaped with the apex directed toward the central core; the nuclei of the cells participating in the rosette are peripherally positioned and form a ring or halo around the hub.
A type of rosette in which a halo of cells surrounds an empty lumen.
A type of rosette in which a spoke-wheel arrangement of cells with tapered cellular processes radiates around a wall of a centrally placed vessel.
A type of rosette that is similar to the Homer Wright rosette, but the central fiber-rich neuropil island is larger and more irregular.
Ocular flutter is an abnormal eye movement consisting of repetitive, irregular, involuntary bursts of horizontal saccades without an intersaccadic interval. It is generally superimposed on normal oculomotor behaviour and its occurrence may be favoured by various events, such as blinks, the triggering of normal saccades or optokinetic stimulation.
Aorto-left ventricular tunnel (ALVT) is a congenital extracardiac channel connecting the ascending aorta above the sino-tubular junction to either left ventricular cavity.
The presence of an extracardiac channel that connects the ascending aorta above the sinotubular junction to the cavity of the right ventricle.
A structural abnormality of the part of the aorta that begins at the aortic arch and then descends through the chest and abdomen.
Significant luminal narrowing of a long segment of or the entire ascending aorta.
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Any structural anomaly of the conus terminalis, which is the distal bulbous part of the spinal cord at the location where the spinal cord tapers and ends (usaully between the L1 and L2 lumbar vertebrae).
Any structural anomaly of the portal venous sytem, which comprises all of the veins draining the abdominal part of the digestive tract, including the lower esophagus but excluding the lower anal canal. The portal vein conveys blood from viscera and ramifies like an artery at the liver, ending at the sinusoids. Tributaries of the portal vein, which make up the portal venous system, are the splenic, superior mesenteric, left gastric, right gastric, paraumbilical, and cystic veins.
Anomaly where the intestinal and the splenic venous drainage bypass the liver and drain into systemic veins through other possible venous shunts.
A state of moror restlessness, usually in the lower extremities, that is often but not always accompanied by a subjective sense of inner restlessness, an urge to move, and anxiety or dysphoria.
An increase in the thickness of the pleura, generally related to scarring of the pleural tissue.
An increased concentration of N,N-dimethylglycine in the circulation.
An increased concentration of N,N-dimethylglycine in the urine.
An unintentional, oscillating to-and-fro muscle movement affecting the tongue.
Centrally located corpus callosum hyperintensities said to resemble snowballs upon magnetic resonance imaging (with T2 or Sagittal fluid attenuated inversion recovery [FLAIR] sequences). The central location in the callosum makes them pathognomonic for Susac syndrome.
An increased susceptibility to bacterial upper respiratory tract infections as manifested by a history of recurrent bacterial upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Temporal and spatial heterogeneity in lungs based on presence of fibrosis and honeycombing.
Seizures that occur while the affected individual is sleeping.
Lumbar spinal stenoses may induce symptoms following an individually typical latency on standing or when walking due to swelling of the cauda equina, which leads to compression. This is referred to as neurogenic claudication. The symptoms of lumbar spinal stenosis can be explained by an increase in lumbar lordosis and spinal canal stenosis in an upright position compared to the sitting position or if spondylolisthesis is present by a shift of the vertebrae while standing and walking. Following an individually characteristic distance, walking becomes associated with deep muscular pain and with neurological deficits, such as sensory deficits and paresis in the lower limbs, which resolve within minutes when the affected person sits or lies down. Activities performed in a flexed posture, such as cycling often cause less problems than walking. For the same reason, walking uphill may be tolerated better than walking downhill. Clinical neurological examination at rest may be entirely normal but there is usually pain on hyperextension of the lumbar spine.
Cautious gait refers to an excessive degree of age-related changes in walking and fear of falling. The walking difficulties seem out of proportion when considering the patient's actual sensory or motor deficits. The gait appears slow, with a wider base than normal, reduced arm swing bilaterally and a slightly stooped posture. This type of gait change often occurs after the first time a patient has fallen.
Dystonic gait disorders frequently appear bizarre, particularly because activity increases dystonic tonus and posture. The abnormal posture of the foot in dystonic gait typically involves inversion, plantar flexion and tonic extension of the big toe. In many patients complex types of walking, such as walking backwards and running are paradoxically less impaired than walking forward and may seem completely unaffected. Sensory tricks, for instance, if the affected individual rests a hand on his or her neck, may improve or even normalize dystonic gait in some patients.
To avoid pain weight is put on the affected leg for as short a time as possible, resulting in a limp. The patients appear to be walking as if there were a thorn in the sole of the foot. To reduce the load on the affected leg the patients lift and lower their foot in a fixed ankle position.
An abnormally high concentration in the circulation of aspartate aminotransferase (AST).
Spastic hemiparesis is characterized by a dominance of the tonus in the upper limb flexor muscles: the arm is held in an adducted posture and is bent and rotated inwards, the forearm is pronated and the hand and the fingers are flexed. The leg is slightly bent at the hip, the knee cannot be extended fully at the end of the stance phase and the foot is inverted and in a plantar flexed position. Gait is slow, with a wide base and asymmetrical with a shortened weight-bearing phase on the paretic side. During the swing phase, the paretic leg performs a lateral movement (circumduction) which is characteristic of this gait disorder, also termed Wernicke-Mann gait. Spastic gait problems typically worsen on attempts to walk faster.
A type of spastic gait in which the legs are usually slightly bent at the hip and in an adducted position. The knees are extended or slightly bent and the feet are in a plantar flexion position. This posture requires circumduction of the legs during walking. The gait may appear stiff (spastic gait disorder) or stiff as well as insecure (spastic ataxic gait disorder). In spastic paraparetic gait, each leg appears to be dragged forward. If the muscle tone in the adductors is marked, the resulting gait disorder is referred to as scissor gait.
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the legs.
A type of dystonia (abnormally increased muscular tone causing fixed abnormal postures) that affects muscles of the arms.
Any deviation from the normal value of the serum anion gap, which is calculated from the electrolytes measured in the chemical laboratory, is defined as the sum of serum chloride and bicarbonate concentrations subtracted from the serum sodium concentration.
An abnormally high value of the serum anion gap (the sum of serum chloride and bicarbonate concentrations subtracted from the serum sodium concentration).
An abnormally low value of the serum anion gap (the sum of serum chloride and bicarbonate concentrations subtracted from the serum sodium concentration).
An abnormally high concentration in the circulation of alanine aminotransferase (ALT), which is an enzyme that catalyzes the transfer of amino groups to form the hepatic metabolite oxaloacetate. ALT is found abundantly in the cytosol of the hepatocyte. ALT activity in the liver is about 3000 times that of serum activity. Thus, in the case of hepatocellular injury or death, release of ALT from damaged liver cells increases measured ALT activity in the serum. Although it is generally thought to be specific to the liver, it is also found in the kidney, and, in much smaller quantities, in heart and skeletal muscle cells.
Red blood cell distribution width (RDW) is a simple parameter of the standard full blood count and a measure of heterogeneity in the size of circulating erythrocytes. It is provided by automated hematology analyzers and it reflects the range of the red cell size. It is calculated by dividing the standard deviation of erythrocyte volume by the mean corpuscular volume (MCV) and multiplied by 100 to convert to a percentage.
The appearance of the urine having visible material in suspension, i.e., appearing cloudy.
An abnormally low concentration of urea nitrogen in the blood.
Any deviation from the normal concentration of urea nitrogen in the blood.
A localized hypertrophy of the subaortic segment of the ventricular septum has been frequently described in elderly persons, and variously termed subaortic ventricular septal bulge (VSB), sigmoid-shaped septum, localized or discrete upper septal hypertrophy.
Presyncope is a state of lightheadedness, muscular weakness, blurred vision, and feeling faint. Presyncope is most often cardiovascular in cause.
An abnormal increase in the ratio of the height of the cup of the optic nerve head to the height of the disc.
Ratio of the height of the cup of the optic nerve head to the height of the disc (The normal cup-to-disc ratio is 0.3).
Ratio of the height of the cup of the optic nerve head to the height of the disc is 0.7 (The normal cup-to-disc ratio is 0.3).
Ratio of the height of the cup of the optic nerve head to the height of the disc is 0.8 (The normal cup-to-disc ratio is 0.3).
Ratio of the height of the cup of the optic nerve head to the height of the disc is 0.9 (The normal cup-to-disc ratio is 0.3).
Ratio of the height of the cup of the optic nerve head to the height of the disc is 1.0 (The normal cup-to-disc ratio is 0.3).
Any deviation from the normal concentration of a carbohydrate in the urine.
Any deviation from the normal concentration of a carboxylic acid in the urine.
An increased concentration of glycolate in the urine.
Any structural anomal of the putamen, a brain nucleus which together with the caudate nucleus and fundus striati makes up the striatum.
This term groups terms representing abnormal findings derived from chest X-ray investigation of the lung. In general, lung abnormalities can manifest as opacities (areas of increased density) or as regions with decreased density.
A piece of food that has gotten stuck in the esophagus and prevents further swallowing.
An exudate is a mass of fluid and cells that has seeped out of blood vessels or an organ, usually related to inflammation. In the esophagus, exudates usually present as whitish plagues on the surface of the esophageal mucosa.
Irregular, small-amplitude myoclonic movements of the hands and/or fingers on keeping outstretched posture (jerky postural tremor). Polyminimyoclonus is stimulus-sensitive and accentuated during voluntary movements. A cortical origin can be demonstrated by back-averaging techniques, and somatosensory evoked potentials (SSEPs) are sometimes giant.
Being unable to focus one's attention or mental effort on a particular object or activity.
A sudden involutanry contraction of a muscle or group of muscles.
A sudden involutanry contraction of the musculature surrounding the mouth.
A contraction of ipsilateral facial muscles subsequent to percussion over the facial nerve.
An increased concentration of beta-1-galactosyl-O-hydroxylysine (Gal-Hyl) in the urine. This is a biochemical marker of bone resorption.
Apical hypertrophic cardiomyopathy (AHCM) is diastolic dysfunction due to abnormal stiffness of the left ventricle during diastole, with resultant impaired ventricular filling. In AHCM thickened apical segments produce a crowded, spade-shaped, small apical cavity.
A Hoffman test is performed by flicking the fingernail of the long finger, from dorsal to volar, on each hand while the hand was supported by the examiner's hand. The test was done with the neck in the neutral position and then with the neck maximally forward flexed. Any flexion of the ipsilateral thumb and/or index finger was interpreted as a positive test.
Bronchial breath sounds contain much higher frequency components than normal breath sounds due to alteration of the low pass filtering function of the alveoli, as occurs in consolidation. It is loud, hollow, and high pitch. Expiratory phase is longer than inspiratory phase with the inspiratory-expiratory ratio (I:E) changing from normal 3:1 to 1:2. There is distinct pause between inspiration and expiration due to absent alveolar phase. It is associated with whispering pectoriloquy.
Squawks are short inspiratory wheezes of less than 200 msduration and are also known as squeaks. Acoustic analysis shows the fundamental frequency varying between 200 and 300 Hz. Squawks usually occur in late inspiration and areoften preceded by late inspiratory crackles.
Crackles that are heard during the inspiratory phase.
Crackles that appear at the beginning of inspiration and end before mid-inspiration.
Crackles that appear any time after the beginning of inspiration and last till the end of inspiration.
An abnormal breath sound that is nonmusical, short and explosive. It is grating, rubbing, creaky, or leathery in character and present in both phases of respiration. Typically the expiratory component mirrors the inspiratory component. It occurs due to inflamed pleural surface rubbing each other during breathing. Clinically, it is important to differentiate it from crackles
A sensation of itching in the vulvar region.
Hemidystonia refers to dystonia which involves the ipsilateral face, arm, and leg.
An unintentional, oscillating to-and-fro muscle movement affecting the lip.
A softening and breaking down of skin resulting from prolonged exposure to moisture. Macerated skin becomes soft and wrinkly and takes on a whitish hue.
The release of fat globules into the venous circulation, thereby blocking blood circulation to the lung.
Constant exotropia occurring before 6 months of age.; often associated with a large angle of deviation and ocular/CNS abnormalities.
Constant exotropia for near and distance, presenting after 6 months of age.
Heterophorias are latent deviations that are controlled by fusion. In certain circumstances (specific visual tasks, fatigue, illness, etc.), fusion can no longer be maintained and decompensation occurs.
Manifest deviation of the visual axes not controlled by fusion.
Overshoot of horizontal (sideways) saccadic eye movements.
Inaccurate saccades (rapid movement of the eye between fixation points) in the vertical direction.
Inaccurate saccades (rapid movement of the eye between fixation points) in the horizontal direction.
An abnormal area of increased brightness (hyperintensity) that is limited to one particular area.
An abnormal area of increased brightness (hyperintensity) that occurs in several distinct areas.
Areas of brighter than expected MRI signal in the white matter of the brain whereby individual patches run together.
A decrease in the level of 1,5 anhydroglucitol in the serum. 1,5-Anhydrosorbitol is a validated marker of short-term glycemic control. This substance is derived mainly from food, is well absorbed in the intestine, and is distributed to all organs and tissues.
An increase in the level of allantoin in the serum.
An increase in the level of GABA in the serum.
A decrease in the level of GABA in the serum.
A decrease in the level of erythritol in the urine.
A decrease in the level of erythritol in the cerebrospinal fluid.
An increase in the level of D-threitol in the plasma.
An increase in the level of D-threitol in the cerebrospinal fluid.
An increase in the level of D-threitol in the urine.
A decrease in the level of D-mannose in the urine.
An increase in the level of galactitol in the plasma.
An increase in the level of galactitol in the urine.
An increase in the level of galactonate in the red blood cells.
An increase in the level of galactitol in the red blood cells.
An increase in the level of hippuric acid in the blood.
An increase in the level of hippuric acid in the urine.
An increase in the level of L-fucose in the urine.
An increase in the level of L-glutamic acid in the blood.
An increase in the level of propylene glycol in the blood.
An increase in the level of ribitol in the urine.
An increase in the level of ribitol in the cerebral spinal fluid.
An increase in the level of ribose in the urine.
An increase in the level of ribose in the cerebrospinal fluid.
An increase in the level of xylitol in the urine.
An increase in the level of xylitol in the cerebrospinal fluid.
An increase in the level of L-pyroglutamic acid in the urine.
Urticaria characterized by spontaneously recurring hives for 6 weeks or longer.
Urticaria caused by physical agents, such as heat, cold, light, friction.
Urticaria may be caused by cold temperatures.
A form of physical urticaria, in which contact with water, regardless of its temperature and source, evokes pruritic follicular wheals on the skin.
Urticaria in response to exposure to ultraviolet-A (UVA), ultraviolet-B (UVB), visible and rarely infrared light.
Urticaria in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum.
An abnormality in biotinidase activity, an enzyme that releases biotin from biocytin, the product of biotin-dependent carboxylases degradation.
A decrease in biotinidase activity, an enzyme that releases biotin from biocytin, the product of biotin-dependent carboxylases degradation.
An increase in biotinidase activity, an enzyme that releases biotin from biocytin, the product of biotin-dependent carboxylases degradation.
Infiltration of eosinophils in the stomach mucosa, that is diagnosed by an upper endoscopy and microscopy that shows more than 20 eosinophils per high-power field in association with peripheral eosinophilia and the absence of secondary cause of eosinophilia.
A rare form of anaphylaxis for which triggers cannot be identified despite a detailed history and careful diagnostic assessment.
Infiltration of numerous eosinophils (usually greater than 15 per high power field) into the squamous epithelium of the esophagus, and layering of eosinophils on the surface layer of the esophagus.
The formation of small localized collection of eosinophiles (an eosinophilic microabscess) in the esophagus. Usually clusters of greater than or equal to 4 eosinophils are seen, that appear as exudates or white spots or white plaques.
An increase in the level of methylsuccinic acid in the urine.
An increase in the level of myristic acid in the serum.
An increase in the level of N-acetylneuraminic acid in the urine.
An increase in the level of N-acetylneuraminic acid in cultured fibroblasts.
An increase in the level of O-phosphoethanolamine in the urine.
A defect in the of the process of interstrand cross-link repair: removal of a DNA interstrand crosslink (a covalent attachment of DNA bases on opposite strands of the DNA) and restoration of the DNA. DNA interstrand crosslinks occur when both strands of duplex DNA are covalently tethered together (e.g. by an exogenous or endogenous agent), thus preventing the strand unwinding necessary for essential DNA functions such as transcription and replication.
Any abnormality of the shoulder muscles.
Partial or complete wasting (loss) of hippocampus tissue that was once present.
Increased concentration of cotinine in urine.
An increased concentration of tropnin I in the blood, which is a cardiac regulatory protein that controls the calcium mediated interaction between actin and myosin. Raised cardiac troponin concentrations are now accepted as the standard biochemical marker for the diagnosis of myocardial infarction.
An increased concentration of tropnin T in the blood, which is a cardiac regulatory protein that controls the calcium mediated interaction between actin and myosin. Raised cardiac troponin concentrations are now accepted as the standard biochemical marker for the diagnosis of myocardial infarction.
An increase in the level of ketone bodies in the blood.
An anomaly in the level of glucose-6-phosphate dehydrogenase.
An anomaly in the level of glucose-6-phosphate dehydrogenase in the blood.
An increase in the level of glucose-6-phosphate dehydrogenase in the blood.
A decrease in the level of glucose-6-phosphate dehydrogenase in the blood.
An anomaly in the level of glucose-6-phosphate dehydrogenase in a dried blood spot.
An increase in the level of glucose-6-phosphate dehydrogenase in a dried blood spot.
A decrease in the level of glucose-6-phosphate dehydrogenase in a dried blood spot.
An anomaly in the level of glucose-6-phosphate dehydrogenase in leukocytes.
An anomaly in the level of glucose-6-phosphate dehydrogenase in red blood cells.
An anomaly in the level of glucose-6-phosphate dehydrogenase in tissue.
An increase in the level of glucose-6-phosphate dehydrogenase in tissue.
A decrease in the level of glucose-6-phosphate dehydrogenase in tissue.
A decrease in the level of glucose-6-phosphate dehydrogenase in red blood cells.
An increase in the level of glucose-6-phosphate dehydrogenase in red blood cells.
A decrease in the level of glucose-6-phosphate dehydrogenase in leukocytes.
An increase in the level of glucose-6-phosphate dehydrogenase in leukocytes.
An abnormality in uridine diphosphate glucose-4-epimerase activity, an enzyme that catalyzes the reaction: UDP-glucose = UDP-galactose.
An abnormality in uridine diphosphate glucose-4-epimerase activity in plasma. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose.
An increase in uridine diphosphate glucose-4-epimerase activity in plasma. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose.
A decrease in uridine diphosphate glucose-4-epimerase activity in plasma. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose.
An abnormality in uridine diphosphate glucose-4-epimerase activity in red blood cells. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose.
An increase in uridine diphosphate glucose-4-epimerase activity in red blood cells. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose.
A decrease in uridine diphosphate glucose-4-epimerase activity in red blood cells. Uridine diphosphate glucose-4-epimerase catalyzes the reaction: UDP-glucose = UDP-galactose.
Increased concentration of urate in the cerebrospinal fluid.
Detection of barbiturate metabolites such as phenobarbital in meconium.
Detection of barbiturate metabolites such as phenobarbital in the hair.
Detection of barbiturate metabolites such as phenobarbital in the stool.
Detection of barbiturate metabolites such as phenobarbital in the gastric fluid.
Any abnormality in the proportion natural killer subsets relative to the total number of natural killer cells.
A mass of granulation tissue in response to chronic dacryocystitis as polypoid formations or they follow accidental injury, from probing and as a reaction to retained foreign bodies in the sac.
The malignant epithelial neoplasm with papillary growths in the nasolacrimal sac.
An abnormality of the conjuctiva and ocular surface caused by conjunctival inflammation and associated with scarring.
A benign tumor composed of adipose tissue and dense connective tissue usually located near the temporal fornix.
A condition where one or both of the two principal meridians focus in the front of the retina when the eye is at rest.
A term to describe when farsightedness is masked when the accommodative muscles are used to increase the focusing power of the eye.
With the eyes in primary position, the sclera is visible above the superior corneal limbus.
An elevation of the eyelid above the normal level in the primary position.
A unilateral or bilateral eyelid retraction due to midbrain lesions.
Inflamation of the eyelid due to overactivity of the sebaceous gland.
A type of lymphoma that involves the nasolacrimal sac.
A very common condition in which the extreme end of the nasolacrimal duct underneath the inferior turbinate fails to complete its canalization in the newborn period.
An avascular or abnormally vascularized retina that occurs in premature infants and can lead to blindness.
The retinal vessels stop and then a linear flat white line is present that usually runs the circumference of the vascular retina.
The accumulating neovascularization thickens and manifests as a linear bump. The neovascularization remains along the surface of the retina and does not extend off the retina into the cortical vitreous.
The neovascularization accumulates at the edge of the vascularized retina and extends into the vitreous (also called extra retinal fibrosis proliferation). In cases of Zone 2 and Zone 3, this may be sausage shaped. In more posterior Zone 1 disease, the stage 3 can appear as a direct extension of the normal retinal vessels but extending tangentially over the avascular retina.
Scar tissue that forms a continuous sheet coming up from the edge of the vascularized retina. This scar tissue can grow toward the vitreous base/posterior lens capsule resulting in traction, distortion, and even detachment.
A detachment that involves the peripheral retina that does not extend into the macula.
A detachment that involves the peripheral retina that involves the macula itself. The detachment usually starts in the temporal periphery although can also involve the nasal retina as well.
Funnel detachment from the retina with generally traction in all four quadrants.
An open funnel detachment of the retina with generally traction in all four quadrants.
A closed funnel detachment of the retina with generally traction in all four quadrants.
Retinopathy which extends from the center of the optic disc to twice the distance from the center of the optic disc to the center of the macula.
Retinopathy which extends centrifugally from the edge of zone I to the nasal ora serrata.
Retinopathy which is a residual crescent of retina anterior to zone II.
Venous dilatation and arteriolar tortuosity of the posterior retinal vessels and may later increase in severity to include iris vascular engorgement, poor pupillary dilatation (rigid pupil), and vitreous haze. This definition has been further refined in the later clinical trials in which the diagnosis of plus disease could be made if sufficient vascular dilatation and tortuosity are present in at least 2 quadrants of the eye.
As vascular abnormalities of the posterior pole that are insufficient for the diagnosis of plus disease but that demonstrate more arterial tortuosity and more venous dilatation than normal.
A retinopathy with a 50% likelihood of progressing to retinal detachment. Threshold disease is considered to be present when stage 3 retinopathy of prematurity (ROP) is present in either zone I or zone II, with at least 5 continuous or 8 total clock hours of disease, and the presence of plus disease.
High risk patients who were in Zone 1 (no Plus or stage 3) or Zone 2 with Plus or stage 3 but not both.
The difference between total and manifest myopia.
A type of ectropion associated with orbicularis muscle weakness caused by cranial nerve VII palsy.
A conjuctival lesion composed of adipose tissue and dense connective tissue. Such choristomas of dermal elements are normally found at the outer canthus, and have a gelatinous appearance. Classically, there is an indistinct posterior border (with the lesion frequently extending into the orbit) and a well-demarcated anterior border several millimetres posterior to the limbus.
Eccentric fixation in which the angle of eccentricity equals the objective angle of deviation.
Any deviation from the normal ocular alignment.
An incomitant tendency for an occluded eye to elevate and extort which resolves on uncovering.
A change in horizontal ocular alignment, unrelated to accommodation, that is brought about solely by a change in the balance of visual input from the two eyes.
A type of vertical tropia in which, when one eye is fixing, the other eye is deviated upwards.
A type of vertical phoria in which, in dissociation, the occluded eye deviates upwards.
A type of vertical tropia in which, when one eye is fixing, the other eye is deviated downwards.
A type of vertical phoria in which, in dissociation, the occluded eye deviates downwards.
The term pseudophakia refers to having an artificial lens implanted after the natural eye lens has been removed. During cataract surgery the natural cloudy lens is replaced by an pseudophakia intraocular lens (IOL).
Having a characteristic appearance of a slate gray area of pigmentation within the disc margins that commonly appears along the inferotemporal or temporal neuroretinal rim areas.
Thinning in the layers of the retina and retinal pigment epithelium around the optic nerve.
A benign tumour of meningothelial cells of the meninges that usually occurs in middle age. It is typically unilateral and there is an association with neurofibromatosis type 2.
A capillary hemangioma surrounding the eyeball but within the orbit.
A hamartoma of lymph vessels that usually presents in childhood. It tends to increase in size with head-down posture and with the Valsalva manoeuvre. Superficial lesions are visible as transilluminable cystic spaces of the lid or conjunctiva that may also contain blood. Deep lesions may cause gradual proptosis or present acutely with orbital pain and reduced vision due to haemorrhage.
A mesenchymal tumour that is considered to be the commonest primary orbital malignancy in children. Histologically, it may be differentiated into embryonal, alveolar, and pleomorphic types. It is usually intraconal or within the superior orbit.
Primary food allergies primarily occur as a result (most likely) of gastrointestinal sensitization to predominantly stable food allergens (glycoproteins). A secondary food allergy develops after primary sensitization to airborne allergens (e. g., pollen allergens) with subsequent reactions (due to cross-reactivity) to structurally related often labile allergens in (plant) foods.
Latex allergy is an IgE-mediated immediate hypersensitivity response to natural rubber latex (NRL) protein with a variety of clinical signs ranging from contact urticaria, angioedema, asthma, and anaphylaxis.
Food-induced anaphylaxis is a severe, potentially fatal, systemic allergic reaction that occurs suddenly after contact with an allergy-causing food.
Presence of a xenobiotic in plasma and/or serum.
Presence of a xenobiotic in gastric fluid.
Abnormal decrease in diastolic blood pressure.
Abnormal decrease in systolic blood pressure.
Elevated systolic blood pressure without an elevated blood pressure.
A decrease in diastolic blood pressure (<60 mmHg) without a decrease in systolic blood pressure (> or = to 100 mmHg).
Detection of cocaine or its major metabolite, benzoylecgonine, in urine.
Detection of barbiturate metabolites such as Phenobarbital in urine.
Detection of delta-9-tetrahydrocannabinol (THC) or other cannabinoid metabolites in urine.
Detection of benzodiazepine metabolites, primarily nordiazepam, oxazepam, and temazepam, in urine.
Detection of amphetamine or its metabolites in urine.
Detection of opioids or opioid metabolites in urine.
Abnormal concentration of urobilinogen present in the stool.
An increased amount of urobilinogen present in the stool.
Detection of barbiturate metabolites such as Phenobarbital in blood.
Abnormal concentration of urate in the cerebrospinal fluid (CSF).
Premature ovarian failure-15 is characterized by onset of oligomenorrhea in the third decade of life, with small ovaries, reduced number of follicles, and elevated gonadotropic hormones (Fouquet et al., 2017). For a general phenotypic description and discussion of genetic heterogeneity of premature ovarian failure, see POF1 (311360).
MGRISCE2 is an autosomal recessive disorder characterized by intrauterine growth restriction, poor postnatal growth with short stature and microcephaly, and increased sister chromatid exchange on cell studies. The disorder results from defective DNA decatenation. The pathogenesis of the disorder is similar to that of Bloom syndrome (BLM; 210900), but patients with mutations in the TOP3A gene do not have a malar rash (summary by Martin et al., 2018). For a discussion of genetic heterogeneity of MGRISCE, see Bloom syndrome (BLM; MGRISCE1; 210900)
Autosomal dominant osteopetrosis-3 is characterized by phenotypic variability. Some patients have typical features of osteopetrosis, including fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in bone mineral density, whereas other patients exhibit localized osteosclerosis and generalized osteopenia. OPTA3 represents a relatively malignant form of osteopetrosis in some patients who develop significant pancytopenia and hepatosplenomegaly (Bo et al., 2016). For a discussion of genetic heterogeneity of autosomal dominant osteopetrosis, see OPTA1 (607634).
Spermatogenic failure-30 is characterized by male infertility due to nonobstructive azoospermia or cryptozoospermia. The few sperm that have been observed are immotile and have small heads. Testicular histology in azoospermic patients shows incomplete maturation arrest, with a Sertoli cell-only pattern in some areas (Arafat et al., 2017). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see 258150.
SPGF31 is characterized by male infertility due to oligozoospermia with a high proportion (greater than 90%) of acephalic sperm. Affected couples may overcome infertility with intracytoplasmic sperm injection (Zhu et al., 2018). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see 258150.
MMERV is an episodic acute reversible encephalopathy that occurs in children and is frequently associated with a trigger, such as a febrile illness. Affected individuals have impaired consciousness, delirious behavior, and/or seizures with lip smacking or eye deviation. These changes are associated with white matter lesions in the brain that often occur in the splenium of the corpus callosum, but may occur in surrounding areas. The acute phase of the disorder can be treated with steroids, and most patients make a full neurologic recovery between episodes with no sequelae (summary by Kurahashi et al., 2018).
Spermatogenic failure-32 is characterized by male infertility due to nonobstructive azoospermia. Testicular biopsy has shown absence of spermatogenic cells and a Sertoli cell-only pattern (Choi et al., 2010). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see 258150.
Liddle syndrome is an autosomal dominant form of hypertension characterized by early onset of hypertension associated with hypokalemia, suppressed plasma renin activity, and suppressed secretion of the mineralocorticoid hormone aldosterone (summary by Hansson et al., 1995). For a general phenotypic description and a discussion of genetic heterogeneity of Liddle syndrome, see 177200.
Ovarian dysgenesis-7 is characterized by primary amenorrhea, delayed puberty, elevated gonadotropic hormones, and small uterus and ovaries. Ovarian histology shows fibrotic ovaries without follicles (Chen et al., 2018). For a discussion of genetic heterogeneity of ovarian dysgenesis, see ODG1 (233300).
BMFS4 is an autosomal recessive disorder characterized by early-onset anemia, leukopenia, and decreased B cells, resulting in the necessity for red cell transfusion and sometimes causing an increased susceptibility to infection. Some patients may have thrombocytopenia or variable additional nonhematologic features, such as facial dysmorphism, skeletal anomalies, and mild developmental delay. Bone marrow transplantation is curative (summary by Bahrami et al., 2017). For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675).
Postaxial polydactyly type 8A is characterized by the presence of postaxial extra digits (hexadactyly) on the hands and/or the feet. The anomalous digits are well formed and have nails (Palencia-Campos et al., 2017). For a discussion of genetic heterogeneity of postaxial polydactyly, see 174200.
Liddle syndrome, or pseudoaldosteronism, is an autosomal dominant form of salt-sensitive hypertension characterized by suppressed plasma renin and aldosterone, hypokalemia, and metabolic alkalosis (summary by Salih et al., 2017). For a discussion of genetic heterogeneity of Liddle syndrome, see 177200.
Autosomal recessive peripheral neuropathy with or without impaired intellectual development is an early childhood-onset neurologic disorder characterized by slowly progressive distal motor impairment resulting in gait difficulties, often with loss of ambulation, and difficulties using the hands in most patients. Most affected individuals also have impaired intellectual development, although some have normal cognition. Electrophysiologic testing and sural nerve biopsy are most compatible with an axonal motor neuropathy; some patients may show signs of demyelination. Additional features may include eye movement abnormalities, claw hands, foot deformities, and scoliosis (summary by Ylikallio et al., 2017).
Autosomal dominant limb-girdle muscular dystrophy-4 is characterized by onset of proximal muscle weakness in young adulthood. Affected individuals often have gait difficulties; some may have upper limb involvement. Other features include variably increased serum creatine kinase, myalgia, and back pain. The severity and expressivity of the disorder is highly variable, even within families (summary by Vissing et al., 2016). For a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see 603511.
Immunodeficiency-58 is an autosomal recessive primary immunologic disorder characterized by early-onset skin lesions, including eczematous dermatitis, infectious abscesses, and warts, recurrent respiratory infections or allergies, and chronic persistent infections with candida, Molluscum contagiosum, mycobacteria, EBV, bacteria, and viruses. Some patients may have gastrointestinal involvement, including inflammatory bowel disease, EBV+ smooth muscle tumors, and esophagitis. Immunologic analysis shows defective T-cell function with decreased Treg cells and deficient CD3/CD28 costimulation responses in both CD4+ and CD8+ T cells. B-cell function may also be impaired (summary by Wang et al., 2016 and Alazami et al., 2018).
MDDGC8 is an autosomal recessive muscular dystrophy with onset in childhood. The phenotype is highly variable: some patients may have gait difficulties and impaired intellectual development, whereas others may be clinically asymptomatic. Common features include calf hypertrophy and increased serum creatine kinase, and muscle biopsy often shows dystrophic features (summary by Endo et al., 2015). The disorder is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007). For a discussion of genetic heterogeneity of muscular dystrophy- dystroglycanopathy type C, see MDDGC1 (609308).
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2), or Nasu-Hakola disease, is a recessively inherited presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years (summary by Klunemann et al., 2005). For a discussion of genetic heterogeneity of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, see 221770.
Intellectual developmental disorder and retinitis pigmentosa is characterized by mild to moderate intellectual disability and typical features of RP. Patients experience reduced night vision, constriction of visual fields, and reduced visual acuity; optic disc pallor, attenuated retinal blood vessels, and bone-spicule pigmentation are seen on funduscopy. Attention-deficit/hyperactivity disorder is observed in some patients (Tatour et al., 2017).
Capillary malformation-arteriovenous malformation-2 (CMAVM2) is an autosomal dominant disorder with variable expressivity. Patients have small multifocal cutaneous capillary malformations (CMs) on the head, neck, trunk, and/or extremities, sometimes in association with arteriovenous malformations (AVMs), which are typically located in the brain, face, or extremities. Some affected individuals also exhibit Parkes Weber lesions of the extremities, and vein of Galen aneurysmal malformations (VGAMs) are present in some patients (Amyere et al., 2017). For a discussion of genetic heterogeneity of CMAVM, see 608354.
Congenital hypomyelinating neuropathy-2 is an autosomal dominant neurologic disorder characterized by early-onset hypotonia, severely delayed motor development, muscle weakness with areflexia, and severely decreased nerve conduction velocities (NCV) resulting from improper myelination of axons. The severity is variable: some patients may present at birth with contractures and respiratory insufficiency, whereas others may achieve walking (summary by Warner et al., 1996). CHN shows significant phenotypic overlap with Dejerine-Sottas syndrome (DSS; 145900), which is also a neuropathy with early onset. Some classify the disorders differently, noting that CHN is characterized by hypo- or amyelination resulting from a congenital defect in myelin formation, whereas DSS has features of continuous myelin breakdown, with demyelination and remyelination (summary by Smit et al., 2008). For a discussion of genetic heterogeneity of CHN, see CHN1 (605253).
Congenital hypomyelinating neuropathy-3 is an autosomal recessive neurologic disorder characterized by onset of neurogenic muscle impairment in utero. Affected individuals present at birth with severe hypotonia, often causing respiratory insufficiency or failure and inability to swallow or feed properly. They have profoundly impaired psychomotor development and may die in infancy or early childhood. Those that survive are unable to sit or walk. Sural nerve biopsy shows hypomyelination of the nerve fibers, and brain imaging often shows impaired myelination and cerebral and cerebellar atrophy. Nerve conduction velocities are severely decreased (about 10 m/s) or absent due to improper myelination (summary by Vallat et al., 2016 and Low et al., 2018). For a discussion of genetic heterogeneity of CHN, see CHN1 (605253).
EIEE68 is an autosomal recessive disorder characterized by onset of twitching and/or myoclonic jerks in infancy. The disorder progresses to refractory generalized tonic-clonic seizures, often resulting in status epilepticus, loss of developmental milestones, and early death. Other features include delayed development, axial hypotonia, spasticity of the limbs, and clonus. Brain imaging may show cortical atrophy (summary by Barel et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Immunodeficiency 15A is an autosomal dominant primary immunodeficiency disorder characterized by relatively late onset of recurrent respiratory tract infections and lymphopenia, combined with immune activation of both CD4+ and CD8+ T cells. One patient presented with inflammatory disease and possible ectodermal defect.
Snijders Blok-Campeau syndrome (SNIBCPS) is an autosomal dominant neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development and delayed speech acquisition. Affected individuals tend to have expressive language deficits, with speech apraxia and dysarthria. Other features include macrocephaly and characteristic facial features, such as prominent forehead and hypertelorism, hypotonia, and joint laxity. The severity of the neurologic deficits and presence of nonneurologic features is variable (summary by Snijders Blok et al., 2018).
Postaxial polydactyly type A9 is characterized by one or more posterior or postaxial digits. There is intrafamilial and intraindividual variability (Schrauwen et al., 2018).
MRT66 is a nonsyndromic autosomal recessive intellectual developmental disorder with delayed speech development, neuropsychiatric symptoms, and relatively normal life span (Philips et al., 2017).
Vertebral anomalies and variable endocrine and T-cell dysfunction is a syndrome characterized by an overlapping spectrum of features. Skeletal malformations primarily involve the vertebrae, and endocrine abnormalities involving parathyroid hormone (PTH; 168450), growth hormone (GH1; 139250), and the thyroid gland have been reported. T-cell abnormalities have been observed, with some patients showing thymus gland aplasia or hypoplasia. Patients have mild craniofacial dysmorphism, and some show developmental delay or behavioral problems. Cardiac defects may be present (Liu et al., 2018).
Epidermodysplasia verruciformis (EV) is a rare genodermatosis associated with a high risk of skin cancer. EV results from an abnormal susceptibility to specific related human papillomavirus (HPV) genotypes and to the oncogenic potential of some of them, mainly HPV5. Infection with EV-associated HPV leads to the early development of disseminated flat wart-like and pityriasis versicolor-like lesions. Patients are unable to reject their lesions, and cutaneous Bowen carcinomas in situ and invasive squamous cell carcinomas develop in about half of them, mainly on sun-exposed areas (summary by Ramoz et al., 2000). For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400).
Baker-Gordon syndrome (BAGOS) is a neurodevelopmental disorder characterized by infantile hypotonia, ophthalmic abnormalities, moderate to profound global developmental delay, poor or absent speech, behavioral abnormalities, hyperkinetic movements, and EEG abnormalities in the absence of overt seizures (summary by Baker et al., 2018).
Although mitochondria and mitochondrial DNA (mtDNA) are typically maternally inherited, evidence exists for rare occurrences of paternal mtDNA transmission (Luo et al., 2018).
DFNB112 is characterized by postlingual progressive sensorineural hearing impairment (Girotto et al., 2013).
Primary ciliary dyskinesia-39 (CILD39) is an autosomal recessive disorder characterized by chronic sinopulmonary infections beginning soon after birth and laterality defects in about 50% of patients. Although patient nasal ciliary samples have normal structure, detailed studies may show ciliary kinetic defects in some patients (summary by Bonnefoy et al., 2018). For a phenotypic description and a discussion of genetic heterogeneity of primary ciliary dyskinesia, see 244400.
GPIBD18 is a severe autosomal recessive developmental disorder characterized by severely impaired global development, hypotonia, weakness, ataxia, coarse facial features, and intractable seizures. More variable features may include abnormalities of the hands and feet, inguinal hernia, and feeding difficulties. The disorder is part of a group of similar neurologic disorders resulting from biochemical defects in the glycosylphosphatidylinositol (GPI) biosynthetic pathway (summary by Nguyen et al., 2018). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
An atypical form of Usher syndrome, here designated type IV, is an autosomal recessive disorder characterized by late onset of retinitis pigmentosa and usually late-onset of progressive sensorineural hearing loss without vestibular involvement (summary by Khateb et al., 2018). For a discussion of genetic heterogeneity of Usher syndrome, see 276900.
DFNB111 is characterized by early-onset, moderate to severe sensorineural hearing loss with no vestibular involvement (Wesdorp et al., 2018; Bademci et al., 2018).
Saul-Wilson syndrome is a rare skeletal dysplasia with characteristic dysmorphic and radiographic findings, as well as early developmental delay, primarily involving speech, with eventual normal cognition. Clinical findings include marked short stature, prominent forehead with an enlarged anterior fontanel, prominent eyes with cataracts, narrow nasal bridge with a convex nasal ridge, micrognathia, clubfoot, brachydactyly, and short distal phalanges of fingers. Radiographic changes include platyspondyly, irregular end plates of vertebral bodies, and hypoplasia of the odontoid process with cervical instability in the spine, coxa valga, overtubulation, metaphyseal flaring and megaepiphyses in the long bones, while the hands and feet exhibit short phalanges, metacarpals and metatarsals, cone-shaped epiphyses of phalanges, and accessory ossification centers of metacarpals and metatarsals (summary by Ferreira et al., 2018).
Spermatogenic failure-33 is characterized by multiple morphologic abnormalities of the flagella (MMAF), resulting in immotile spermatozoa and infertility. Short and irregular-caliber flagella are primarily observed, as well as absent and coiled flagella, and abnormalities of the acrosome, head, and base are also present (Kherraf et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Spermatogenic failure-34 is characterized by multiple morphologic abnormalities of the flagella (MMAF), resulting in immotile spermatozoa and infertility. Irregular-caliber, short, and coiled flagella are primarily observed, as well as absent flagella, and abnormalities of the axoneme are also present (Martinez et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of spermatogenic failure, see SPGF1 (258150).
Hennekam lymphangiectasia-lymphedema syndrome-3 (HKKLLS3) is characterized by widespread congenital edema that is more severe in more dependent areas of the body. Associated features include facial dysmorphism and protein-losing enteropathy of variable severity (Brouillard et al., 2017). For a discussion of genetic heterogeneity of Hennekam lymphangiectasia-lymphedema syndrome, see HKLLS1 (235510).
External ophthalmoplegia with rib and vertebral anomalies is characterized by congenital nonprogressive external ophthalmoplegia and ptosis, with torticollis and scoliosis developing during childhood. In addition, patients exhibit hypoplastic or missing ribs with fusion anomalies (Di Gioia et al., 2018).
Squalene synthase deficiency is an autosomal recessive disorder characterized by profound developmental delay, brain abnormalities, 2/3 syndactyly of the toes, and facial dysmorphisms, as well as low total and LDL-cholesterol and abnormal urine organic acids (Coman et al., 2018). Squalene synthase deficiency has been reported in 3 patients from 2 families.
IGHD type IV is an autosomal recessive disorder characterized by early and severe growth failure (height SDS up to -7.4), a blunted growth hormone (GH) response to different provocation tests and low insulin-like growth factor-I (IGF1; 147440) and IGF-binding protein-3 (IGFBP3; 146732) concentrations, and a good response to growth hormone treatment (summary by Alatzoglou et al., 2014). For general phenotypic information and a discussion of genetic heterogeneity of IGHD, see 262400.
Isolated growth hormone deficiency type V is characterized by severe postnatal growth failure, delayed bone age without bone dysplasia, and hypoplasia of the anterior pituitary (Argente et al., 2014).
Krakow-type spondyloepimetaphyseal dysplasia is characterized by severe skeletal dysplasia, severe immunodeficiency, and developmental delay (Csukasi et al., 2018).
Osteochondrodysplasia, brachydactyly, and overlapping malformed digits (OCBMD) is characterized by bilateral symmetric skeletal defects that primarily affect the limbs. Affected individuals have mild short stature due to shortening of the lower leg bones, as well as hand and foot malformations, predominantly brachydactyly and overlapping digits. Other skeletal defects include scoliosis, dislocated patellae and fibulae, and pectus excavatum (Shabbir et al., 2018).
Bone marrow failure syndrome-5 (BMFS5) is a hematologic disorder characterized by infantile onset of severe red cell anemia requiring transfusion. Additional features include hypogammaglobulinemia, poor growth with microcephaly, developmental delay, and seizures (summary by Toki et al., 2018) For a discussion of genetic heterogeneity of BMFS, see BMFS1 (614675).
Diarrhea-9 is a form of neonatal-onset chronic diarrhea characterized by an osmotic diarrhea that is not substrate specific, abnormal crypt and villus architecture, and significant fat malabsorption (O'Connell et al., 2018). For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
Retinitis pigmentosa-83 (RP83) is characterized by onset of night blindness in the first decade of life, with decreased central vision in the second decade of life in association with retinal degeneration. The retinal dystrophy is associated with cataract, and macular edema has also been reported in some patients (Holtan et al., 2019).
Complex cortical dysplasia with other brain malformations-9 is a severe autosomal recessive disorder characterized by profoundly impaired motor and cognitive development apparent from early infancy. Affected individuals develop intractable seizures and are unable to speak or ambulate. Brain imaging shows pachygyria as well as hypogenesis of the corpus callosum and other variable brain abnormalities. The phenotype results from impaired cortical neuronal migration (summary by Schaffer et al., 2018). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039).
SCA48 is an autosomal dominant neurodegenerative disorder characterized by onset of gait ataxia and/or cognitive-affective symptoms in mid-adulthood. Patients may present with involvement of either system, but most eventually develop impairment in both. Features include gait ataxia, dysarthria, and dysphagia, as well as anxiety and deficits in executive function. Brain imaging shows selective atrophy of the posterior areas of the cerebellar vermis (summary by Genis et al., 2018).
Some ectodermal dysplasias are here classified as congenital disorders characterized by abnormal development in 2 or more ectodermal structures (hair, nails, teeth, and sweat glands) without other systemic findings. Ectodermal dysplasia-14 of the hair/tooth type is primarily characterized by scalp hypotrichosis and hypodontia. Some patients have decreased sweating, and some show subtle facial dysmorphism (Peled et al., 2016).
Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. Patient have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy (summary by Ghosh et al., 2018).
Diarrhea-10 is a protein-losing enteropathy characterized by intractable secretory diarrhea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients (Broekaert et al., 2018; Kurolap et al., 2018). For a discussion of genetic heterogeneity of diarrhea, see DIAR1 (214700).
Periventricular nodular heterotopia-8 (PVNH8) is a neurologic disorder characterized by abnormal neuronal migration during brain development, resulting in delayed psychomotor development. Three patients have been reported (Ge et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of periventricular heterotopia, see PVNH1 (300049).
Orthostatic hypotension-2 is an autosomal recessive disorder characterized by severe orthostatic hypotension, recurrent hypoglycemia, and low norepinephrine levels. The disorder has onset in infancy or early childhood. Some patients may also have renal dysfunction and reduced life expectancy. The disorder results from a defect in the biosynthesis of norepinephrine from dopamine due to a cofactor deficiency. For a discussion of genetic heterogeneity of ORTHYP, see ORTHYP1 (223360).
Transient neonatal hyperparathyroidism is characterized by interference with placental maternal-fetal calcium transport, causing fetal calcium deficiency resulting in hyperparathyroidism and metabolic bone disease. Because 80% of calcium is transferred during the third trimester, abnormalities may not be detected on second-trimester ultrasounds. Affected infants present at birth with prenatal fractures, shortened ribs, and bowing of long bones, as well as respiratory and feeding difficulties. Postnatal recovery or improvement is observed once calcium is provided orally, with most patients showing complete resolution of skeletal abnormalities by 2 years of age (Suzuki et al., 2018).
DFNX7 is a congenital form of bilateral mixed or conductive hearing loss, which may be progressive. It is not associated with vestibular symptoms (Xing et al., 2017).
CMD2C is characterized by dilated cardiomyopathy of variable severity, with age of onset ranging from 2 to 20 years. Affected individuals exhibit reduction in coenzyme A (CoA) levels. Some severely affected children die in the first few years of life (Iuso et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of dilated cardiomyopathy (CMD), see 115200.
Ovarian dysgenesis-8 (ODG8) is characterized by complete lack of estrogen action, resulting in absent breast development, primary amenorrhea, and osteoporosis (Lang-Muritano et al., 2018). For a discussion of genetic heterogeneity of ovarian dysgenesis, see ODG1 (233300).
Oocyte maturation defect-5 is characterized by female infertility due to inability of the oocyte to exit metaphase II, resulting in fertilization failure (Sang et al., 2018). For a discussion of genetic heterogeneity of oocyte maturation defects, see OOMD1 (615774).
Autosomal dominant deafness-74 (DFNA74) is characterized by nonsyndromic postlingual progressive hearing loss, with onset in the third decade of life in most affected individuals (Wang et al., 2018).
MFRG is an autosomal recessive syndrome in which microcephaly, unilateral renal agenesis, ambiguous genitalia, and facial dysmorphisms, including severe micrognathia, are observed in most patients. Variable brain, cardiac, and skeletal anomalies are present, including corpus callosum agenesis or dysgenesis, lissencephaly, atrial and ventricular septal defects, patent ductus arteriosus, hypoplastic right ventricle, and joint contractures (Shaheen et al., 2016).
ACCIID is characterized by arthrogryposis, cleft palate, craniosynostosis, micrognathia, short stature, and impaired intellectual development. Seizures and bony abnormalities (severe slenderness of the ribs and tubular bones and perinatal fractures) have been observed (Mizuguchi et al., 2018).
Trichohepatoneurodevelopmental syndrome is a complex multisystem disorder characterized by woolly or coarse hair, liver dysfunction, pruritus, dysmorphic features, hypotonia, and severe global developmental delay (Morimoto et al., 2018).
Epidermodysplasia verruciformis-3 is characterized by onset in childhood or early adulthood of persistent disseminated flat warts and pityriasis versicolor-like lesions of the skin that are induced by cutaneous human papillomaviruses (HPVs) of the beta genus. Some patients develop nonmelanoma skin cancer, particularly on areas of the body exposed to the sun. Patients are otherwise healthy and normally resistant to other microorganisms, including other viruses and skintropic pathogens, and even all other cutaneous and mucosal HPVs (de Jong et al., 2018). For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400).
Congenital mirror movements-4 is an autosomal dominant condition characterized by involuntary movements on either side of the body that accompany and mirror intentional movements on the opposite side. Mirror movements usually involve the upper limb and hands, resulting in difficulty performing pure unimanual movements. The pathophysiology is probably related to developmental abnormalities of fiber decussation in the corticospinal tract (summary by Meneret et al., 2017). For a discussion of genetic heterogeneity of mirror movements, see MRMV1 (157600).
Hypotrichosis-14 is characterized by sparse to absent lanugo-like scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body hair (Romano et al., 2018). For a discussion of genetic heterogeneity of hypotrichosis, see HYPT1 (605389).
Lymphoproliferative syndrome-3 (LPFS3) is an autosomal recessive early-onset immunologic disorder characterized by increased susceptibility to Epstein-Barr virus (EBV) infection in B cells, resulting in abnormal B-cell proliferation and increased susceptibility to B-cell malignancies, including Hodgkin lymphoma. Patients usually have hypogammaglobulinemia without lymphopenia, although some subsets of immune cells may be low and some patients may have recurrent infections. The disorder results from impaired signaling from proliferating B cells to effector T cells that provide immune surveillance. There may be an increased risk of solid tumors in heterozygous carriers (summary by Abolhassani et al., 2017). For a discussion of genetic heterogeneity of lymphoproliferative syndrome, see XLP1 (308240).
MCCCHCM is an autosomal dominant neurodevelopmental disorder characterized by global developmental delay, impaired intellectual development, and characteristic brain abnormalities on brain imaging. Affected individuals have enlargement of the corpus callosum, enlarged ventricles, and cerebellar and brainstem hypoplasia. Other features may include lack of speech development, gait instability, and seizures. Some patients with MAST1 mutations may have impaired intellectual development and/or autism spectrum disorder without significant findings on brain imaging (summary by Tripathy et al., 2018).
Childhood-onset neurodegeneration with cerebellar atrophy is a severe autosomal recessive neurodevelopmental disorder affecting the central and peripheral nervous system. Patients present in the first year of life with global developmental delay, impaired intellectual development, poor or absent speech, and motor abnormalities. Brain imaging shows cerebellar atrophy. The severity is variable, but death in childhood may occur (summary by Shashi et al., 2018).
Cardiac-urogenital syndrome is characterized by partial anomalous pulmonary venous return in association with tracheal anomalies, pulmonary hypoplasia, congenital diaphragmatic hernia, thyroid fibrosis, thymic involution, cleft spleen, penoscrotal hypospadias, and cryptorchidism (Pinz et al., 2018).
Fibrosis, neurodegeneration, and cerebral angiomatosis is characterized by severe progressive cerebropulmonary symptoms, resulting in death in infancy from respiratory failure. Features include malabsorption, progressive growth failure, recurrent infections, chronic hemolytic anemia, and transient liver dysfunction. Neuropathology shows increased angiomatosis-like leptomeningeal, cortical, and superficial white matter vascularization and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and granuloma-like lesions are seen in the lungs, and there is hepatomegaly with steatosis and collagen accumulation (Uusimaa et al., 2018).
Charcot-Marie-Tooth disease type 1G is an autosomal dominant progressive peripheral sensorimotor neuropathy characterized by distal muscle weakness and atrophy with onset in the first or second decade. Affected individuals have difficulty walking, distal sensory impairment with decreased or absent reflexes, and often have foot deformities. Median motor nerve conduction velocities (NCV) are decreased (less than 38 m/s) and sural nerve biopsy shows myelin defects and onion bulb formation (summary by Hong et al., 2016 and Motley et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant Charcot-Marie-Tooth disease type 1, see CMT1B (118200).
Hyper-IgE recurrent infection syndrome-3 is an autosomal recessive immunologic disorder characterized by childhood onset of atopic dermatitis, skin infections particularly with Staphylococcus aureus, recurrent sinopulmonary infections, and increased serum IgE and IgG. Patients are susceptible to bacterial and fungal infections, including chronic mucocutaneous candidiasis. Immunologic work-up shows impaired differentiation of CD4+ T cells into T-helper 17 cells, decreased memory B cells, and often decreased NK cells (summary by Beziat et al., 2018). For a discussion of genetic heterogeneity of hyper-IgE recurrent infection syndrome, see HIES1 (147060).
Visual impairment and progressive phthisis bulbi is characterized by poor vision at birth, with development of bilateral phthisis by adulthood (Ansar et al., 2018).
The MCIDDS syndrome is characterized by microcephaly and growth retardation, congenital cataracts, impaired intellectual development with attention deficit-hyperactivity disorder, and dystonia, with striatal thinning seen on MRI (Al-Owain et al., 2013).
Infantile epileptic encephalopathy-69 (EIEE69) is an autosomal dominant severe neurodevelopmental encephalopathic disorder characterized by early-onset refractory seizures, hypotonia, and profoundly impaired development often associated with macrocephaly, hyperkinetic movements, and contractures. The disorder can sometimes result in early death. Some patients may have a favorable seizure response to topiramate medication (summary by Helbig et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (308350).
Flurbiprofen (brand name Ansaid) is a nonsteroidal anti-inflammatory drug (NSAID). Tablets and skin patches are used in the management of osteoarthritis and rheumatoid arthritis. Flurbiprofen provides pain relief and reduces inflammation. Flurbiprofen eye drops (brand name Ocufen) may also be used to prevent miosis (excessive constriction of the pupil) during eye operations; e.g., cataract surgery. Flurbiprofen is primarily metabolized by CYP2C9. Individuals who lack CYP2C9 activity (CYP2C9 poor metabolizers) have an increased exposure to flurbiprofen, and an increased risk of side effects. Like all NSAIDs, flurbiprofen increases the risk of serious cardiovascular events, including myocardial infarction and stroke, and serious gastrointestinal (GI) adverse events such as bleeding, ulceration, and perforation, which may be fatal. The recommended starting dose of flurbiprofen tablets in adults is 200–300 mg per day, divided for administration 2, 3, or 4 times a day. But for all patients, the lowest effective dose of flurbiprofen should be used for the shortest length of time, consistent with the treatment goals of each individual. The FDA-approved drug label for flurbiprofen states that the dose of flurbiprofen should be reduced in ""patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin)"". This dose reduction is to avoid the abnormally high plasma levels of flurbiprofen in these patients caused by reduced metabolic clearance. However, specific dose reductions based on CYP2C9 phenotype are not provided. As for all NSAIDs, flurbiprofen is contraindicated in patients with a known hypersensitivity; a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or another NSAID; and for coronary artery bypass graft (CABG) surgery. Flurbiprofen should also be avoided by pregnant women starting at 30 weeks gestation.
SMALED2B is a severe neuromuscular disorder with onset in utero. Affected individuals show decreased fetal movements and are usually born with congenital contractures consistent with arthrogryposis multiplex congenita (AMC). After birth, they have severe hypotonia and muscle atrophy as well as respiratory insufficiency due to muscle weakness. Some patients may have dysmorphic facial features and/or abnormalities on brain imaging. Many patients die in early childhood (summary by Storbeck et al., 2017) For discussion of genetic heterogeneity of lower extremity-predominant spinal muscular atrophy, see SMALED1 (158600).
CILD40 is an autosomal recessive primary ciliary dyskinesia with a relatively mild respiratory phenotype compared to other CILDs. Patients present in childhood with mild upper respiratory symptoms and infections, but typically do not develop serious lung disease. Nitric oxide levels are low-normal or normal. All reported patients have had situs inversus, including several with severe congenital cardiac malformations, but left-right body asymmetry is still theoretically random and would occur in 50% of patients (summary by Loges et al., 2018). For a discussion of genetic heterogeneity of primary ciliary dyskinesia and Kartagener syndrome, see CILD1 (244400).
Epidermodysplasia verruciformis-4 is an autosomal recessive immunologic disorder characterized by increased susceptibility to certain human papilloma viruses (HPV) that cause warts and skin lesions. Affected individuals present in childhood with disseminated flat warts and psoriatic-like lesions that do not respond to treatment. Immunologic workup shows defects in T-cell development and signaling (summary by Crequer et al., 2012). For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400).
Epidermodysplasia verruciformis-5 is an autosomal recessive immunologic disorder characterized by onset of warts and verrucous or plaque-like skin lesions associated with HPV infection. Immunologic workup shows T-cell lymphopenia, particularly affecting CD4+ T cells. There is an increased risk of skin malignancy, and some patients may have other symptoms of immune dysfunction (summary by Horev et al., 2015). For a discussion of genetic heterogeneity of susceptibility to epidermodysplasia verruciformis, see EV1 (226400).
HOMGSMR2 is characterized by generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Seizures persist despite magnesium supplementation, and are associated with significantly impaired intellectual development (Schlingmann et al., 2018). For a discussion of genetic heterogeneity of HOMGSMR, see 616418.
Piroxicam (brand name Feldene) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat osteoarthritis and rheumatoid arthritis. Piroxicam provides pain relief and reduces inflammation. Piroxicam is primarily metabolized by CYP2C9. Individuals who lack CYP2C9 activity (""CYP2C9 poor metabolizers"") have an increased exposure to piroxicam, and an increased risk of side effects. Like all NSAIDs, piroxicam increases the risk of serious cardiovascular events, including myocardial infarction and stroke, and serious gastrointestinal (GI) adverse events such as bleeding, ulceration, and perforation. The standard dose of piroxicam for osteoarthritis and rheumatoid arthritis in adults is 20 mg once daily. But for all patients, the lowest effective dose of piroxicam should be used for the shortest length of time, consistent with the treatment goals of each individual. The FDA-approved drug label for piroxicam states that a dose reduction should be considered in ""patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin)"". Dose reductions should be considered because these patients may have abnormally high plasma levels of piroxicam caused by reduced metabolic clearance. However, specific dose reductions based on CYP2C9 phenotype are not provided. As for all NSAIDs, piroxicam is contraindicated in patients with a known hypersensitivity, a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or another NSAID, and following coronary artery bypass graft (CABG) surgery. Piroxicam should also be avoided by pregnant women starting at 30 weeks gestation.
IDDCDF is an autosomal recessive syndromic neurodevelopmental disorder characterized by globally impaired development with intellectual disability and speech delay, congenital cardiac malformations, and dysmorphic facial features. Additional features, such as distal skeletal anomalies, may also be observed (summary by Stephen et al., 2018).
Autosomal recessive idiopathic basal ganglia calcification-7 is a neurologic disorder characterized by onset of symptoms in adulthood. Patients present with dysarthria, gait abnormalities, various movement abnormalities, and often cognitive decline. Brain imaging shows abnormal accumulation of calcium deposits in deep brain regions, including the basal ganglia, thalamus, dentate nuclei, cerebellum, and sometimes other areas of the brain and spinal cord. Some patients with brain imaging abnormalities may be clinically asymptomatic (summary by Yao et al., 2018). For a detailed phenotypic description and a discussion of genetic heterogeneity of IBGC, see IBGC1 (213600).
The sense of bitter taste is mediated by a group of bitter taste receptor proteins that reside on the surface of taste cells within the taste buds of the tongue. These proteins are 7-transmembrane domain, G protein-coupled receptors that are encoded by the TAS2R gene family (see TAS2R10; 604791), which contains at least 25 functional genes (Kim et al., 2005). Humans worldwide display a bimodality in sensitivity to the bitter taste of PTC, with approximately 75% of individuals perceiving it as intensely bitter, whereas the rest perceive it as tasteless. This difference has been the basis of study of taste perception in humans for over 70 years. Kim and Drayna (2004) provided an historical review of the subject. Propylthiouracil (PROP) and PTC are members of a class of compounds known as thioureas. The compounds carry the chemical group N-C=S, which is responsible for their characteristic bitter taste (Bartoshuk et al., 1994; Drewnowski and Rock, 1995).
Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, and sometimes seizures, resulting in death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions (summary by van Bergen et al., 2019). For a discussion of genetic heterogeneity of PEBEL, see PEBEL1 (617186).
Congenital myasthenic syndrome-25 is an autosomal recessive neuromuscular disorder characterized by hypotonia and generalized muscle weakness apparent from birth. Affected individuals have feeding difficulties and delayed motor development, usually never achieving independent ambulation. Additional variable features include eye movement abnormalities, joint contractures, and rigid spine. Pyridostigmine treatment may be partially effective (summary by Shen et al., 2017). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462).
Lissencephaly-9 is an autosomal dominant neurologic disorder characterized by global developmental delay apparent since infancy, impaired intellectual development with poor or absent speech, and sometimes abnormal or involuntary movements associated with abnormal brain imaging that typically shows pachygyria, lissencephaly, and malformation of the brainstem consistent with a neuronal migration defect (summary by Dobyns et al., 2018). For a general description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Early infantile epileptic encephalopathy-71 (EIEE71) is characterized by early neonatal refractory seizures, respiratory failure, structural brain abnormalities and cerebral edema, with death within weeks after birth. Glutamine levels are significantly increased (z score 3.2-11.7). Three patients have been described (summary by Rumping et al., 2018).
IMAGEI is an autosomal recessive disorder characterized by intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency. Patients exhibit distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency (Logan et al., 2018). An autosomal dominant form of the disorder, without immunodeficiency (IMAGE; 614732), is caused by mutation in the CDKN1C gene (600856) on chromosome 11p15.
Combined oxidative phosphorylation deficiency-37 is an autosomal recessive multisystem disorder apparent at birth or in the first months of life. Affected individuals have hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction. Some patients may have hypertrophic cardiomyopathy, loss of vision and hearing, and/or seizures. Mitochondrial respiratory dysfunction is apparent in liver and skeletal muscle tissue. Most patients die in childhood (summary by Zeharia et al., 2016). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Menke-Hennekam syndrome-1 (MKHK1) is a congenital disorder characterized by variable impairment of intellectual development and facial dysmorphisms. Feeding difficulties, autistic behavior, recurrent upper airway infections, hearing impairment, short stature, and microcephaly are also frequently seen. Although mutations in the same gene cause Rubinstein-Taybi syndrome-1 (RSTS1; 180849), patients with MKHK1 do not resemble the striking phenotype of RSTS1. Genetic Heterogeneity of Menke-Hennekam Syndrome Menke-Hennekam syndrome-2 (MKHK2; 618333) is caused by heterozygous mutation in exons 30 or 31 of the EP300 gene (602700). Mutation elsewhere in that gene results in RSTS2 (613684).
Menke-Hennekam syndrome-2 (MKHK2) is a congenital disorder characterized by variable impairment of intellectual development and facial dysmorphisms. Feeding difficulties, autistic behavior, recurrent upper airway infections, and hearing impairment are also frequently seen. Although mutations in the same gene cause Rubinstein-Taybi syndrome-2 (RSTS2; 613684), patients with MKHK1 do not resemble the striking phenotype of RSTS2. For a discussion of genetic heterogeneity of Menke-Hennekam syndrome, see MKHK1 (618332).
Aside from the clinical features of infantile cataract, skin abnormalities, and impaired intellectual development, CASGID is characterized by strikingly high intracerebral and urinary glutamate excess with almost undetectable glutamine. A gain-of-function mutation in the GLS gene was found (see MOLECULAR GENETICS). GLS loss of function is implicated in a form of neonatal epileptic encephalopathy (EIEE71; 618328) and a syndrome of global developmental delay and progressive ataxia (GDPAG; 618412).
Spermatogenic failure-35 is characterized by multiple morphologic abnormalities of the flagella (MMAF), resulting in spermatozoa with severely impaired motility and infertility. Short, thickened, and coiled flagella are primarily observed, as well as absent flagella, and abnormalities of axonemal composition are also present (Shen et al., 2019).
Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome is an autosomal recessive disorder with a highly variable phenotype. Although all patients have polymicrogyria and other variable structural brain anomalies on imaging, only some show developmental delay and/or seizures. Similarly, only some patients have connective tissue defects that particularly affect the vascular system and can result in early death (summary by Vandervore et al., 2017).
Microcephaly, growth deficiency, seizures, and brain malformations (MIGSB) is a severe autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Additional features include optic atrophy, early-onset seizures, dysmorphic facial features, and brain malformations, such as partial agenesis of the corpus callosum and simplified gyration (summary by Shaheen et al., 2015).
Galloway-Mowat syndrome is a phenotypically heterogeneous disorder characterized by neurodevelopmental defects combined with renal-glomerular disease manifest as nephrotic syndrome and proteinuria. Most patients with GAMOS6 also have growth deficiency with variable microcephaly, and the renal disease may be age-dependent. Additional variable endocrine abnormalities have also been reported (summary by Braun et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Oocyte maturation defect-6 is characterized by primary infertility due to defective sperm-binding to an abnormally thin zona pellucida in patient oocytes. Successful pregnancy may be achieved by intracytoplasmic sperm injection in these patients (Dai et al., 2019).
Galloway-Mowat syndrome-7 (GAMOS7) is an autosomal recessive disorder characterized by developmental delay, microcephaly, and early-onset nephrotic syndrome (summary by Rosti et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Galloway-Mowat syndrome-8 is an autosomal recessive disorder characterized by impaired psychomotor development, poor overall growth with microcephaly, and early-onset progressive nephrotic syndrome associated with focal segmental glomerulosclerosis on renal biopsy. Some patients may have seizures, and some may die in childhood (summary by Fujita et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of GAMOS, see GAMOS1 (251300).
Neurodevelopmental disorder and language delay with or without structural brain abnormalities (NEDLBA) is characterized by global developmental delay apparent from infancy. The phenotype is highly variable: patients may have hypotonia, behavioral abnormalities, and abnormalities on brain imaging, including enlarged ventricles, thin corpus callosum, and sometimes small brainstem. Many develop seizures, sometimes refractory, and some may have nonspecific dysmorphic features. Intellectual impairment can vary from mild to profound, and some patients may benefit from special education and respond well to speech therapy (summary by Reynhout et al., 2019).
Neurodevelopmental disorder with central and peripheral motor dysfunction (NEDCPMD) is an autosomal recessive neurologic disorder with a highly variable phenotype. At the severe end of the spectrum, patients may have hypotonia apparent from birth, necessitating mechanical respiration and tube-feeding, and global developmental delay with absence of reaction to touch and no eye contact. At the mild end of the spectrum, patients may present with infantile-onset progressive ataxia and demyelinating peripheral neuropathy. The disorder is caused by mutation in the NFASC gene, which has several neuronal- and glial-specific transcripts. The variable clinical phenotype may be caused by several factors, including the severity of the mutation, the selective involvement of distinct isoforms by pathogenic variants, and the presence of genetic modifiers (summary by Monfrini et al., 2019).
Susceptibility to idiopathic generalized epilepsy-15 (EIG15) is an autosomal dominant seizure disorder characterized by onset of variable types of seizures in the first decade. Absence seizures are the most common manifestation, but most patients also develop other types, including clonic or generalized tonic-clonic seizures. EEG tends to show 3-Hz spike-wave discharges, whereas brain imaging is normal. The majority of patients also have developmental delay associated with impaired intellectual development apparent from infancy or early childhood (summary by Rudolf et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of idiopathic generalized epilepsy, see EIG (600669).
Cone-rod dystrophy and hearing loss-2 (CRDHL2) is characterized by retinal dystrophy, with photophobia and progressive reduction in visual acuity, associated with sensorineural hearing loss (Kubota et al., 2018). For a discussion of genetic heterogeneity of cone-rod dystrophy and hearing loss, see CRDHL1 (617236).
X-linked neurodevelopmental disorder with craniofacial abnormalities is characterized by global developmental delay with impaired intellectual development and poor speech. Ear abnormalities and hearing loss are common, as are dysmorphic facial features such as microcephaly and cleft palate. Other features may include short stature, scoliosis, vertebral abnormalities, and mild limb abnormalities such as fifth finger clinodactyly. Clinical manifestations depend on the type of mutation: female carriers with missense mutations may be unaffected, and conversely, males with nonsense or truncating mutations may have a severe phenotype with early death (summary by Aoi et al., 2019).
Coffin-Siris syndrome-8 is characterized by variable degrees of impaired intellectual development including speech impairment, hypotonia, feeding difficulties, and behavioral abnormalities. Dysmorphic features may or may not be present and include hypertrichosis or thin scalp hair, thick eyebrows, thin upper vermilion, and upturned nose (Machol et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of Coffin-Siris syndrome, see CSS1 (135900).
Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is characterized by disproportionate short stature, defective tooth enamel formation, and skeletal dysplasia with severe scoliosis in some patients. Variable features include facial dysmorphism, moderate hearing impairment, and mildly impaired intellectual development (Ashikov et al., 2018).
Brain small vessel disease-3 (BSVD3) is an autosomal recessive disorder resulting from fragility of cerebral vessels causing an increased risk of intracranial bleeding. The resultant phenotype is highly variable depending on timing and location of the intracranial bleed. Some patients may have onset in utero or early infancy, with subsequent global developmental delay, spasticity, and porencephaly on brain imaging. Other patients may have normal or mildly delayed development with sudden onset of intracranial hemorrhage causing acute neurologic deterioration (summary by Miyatake et al., 2018). For a discussion of genetic heterogeneity of brain small vessel disease, see BSVD1 (175780).
Autosomal recessive spinocerebellar ataxia-27 (SCAR27) is an adult-onset neurologic disorder characterized by gait difficulties and other cerebellar signs, such as eye movement abnormalities, dysarthria, and difficulty writing. The disorder is progressive, and some patients may lose independent ambulation. Additional features include spasticity of the lower limbs and cognitive impairment. Brain imaging shows cerebellar atrophy (summary by Eidhof et al., 2018).
Turnpenny-Fry syndrome (TPFS) is characterized by developmental delay, impaired intellectual development, impaired growth, and recognizable facial features that include frontal bossing, sparse hair, malar hypoplasia, small palpebral fissures and oral stoma, and dysplastic 'satyr' ears. Other common findings include feeding problems, constipation, and a range of brain, cardiac, vascular, and skeletal malformations (Turnpenny et al., 2018).
CAPOK syndrome is characterized by onset of symptoms in the first year of life, with the development of progressive alopecia, hypo- and hyperpigmented macular skin lesions, palmoplantar keratoderma, and nail dystrophy. Beginning in the third decade of life, patients develop recurrent squamous cell carcinomas. Some patients may have brittle teeth resulting in tooth loss, and multinodular goiter has been observed (Courcet et al., 2015).
The fetal akinesia deformation sequence (FADS) refers to a clinically and genetically heterogeneous constellation of features including fetal akinesia, intrauterine growth retardation, arthrogryposis, and developmental anomalies, including lung hypoplasia, cleft palate, and cryptorchidism (Vogt et al., 2009). It shows phenotypic overlap with the lethal form of multiple pterygium syndrome (see 253290). For a general phenotypic description and a discussion of genetic heterogeneity of FADS, see 208150.
Amelogenesis imperfecta type IIIC is characterized by hypocalcified enamel in both the primary and secondary dentition. The enamel is rough and yellow-brown; under normal use, the enamel disintegrates from occlusal surfaces of the molars, leaving a ring of intact enamel remaining on the sides. Some affected individuals have anterior open bite (Kim et al., 2019).
Acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate (ARLIAK) is an autosomal recessive disorder characterized by acute reversible neurologic deterioration in the context of a febrile illness. The disorder is associated with transient leukoencephalopathy on brain imaging concurrent with the acute episode, as well as persistently increased excretion of dicarboxylic acids, particularly alpha-ketoglutarate (summary by Dewulf et al., 2019).
Spinocerebellar ataxia with axonal neuropathy-3 (SCAN3) is an autosomal recessive neuromuscular disorder characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy and distal sensory impairment due to an axonal peripheral neuropathy. Affected individuals have gait disturbances and sometimes manual dexterity difficulties, as well as cerebellar ataxia associated with cerebellar atrophy on brain imaging. Additional features usually include dysarthria, hyporeflexia, and increased serum creatine kinase. Some patients may have impaired intellectual development (summary by Higuchi et al., 2018). For a discussion of genetic heterogeneity of SCAN, see SCAN1 (607250).
The Kondo-Fu type of spondyloepiphyseal dysplasia (SEDKF) is characterized by severely retarded growth and skeletal anomalies, including spondyloepiphyseal dysplasia with associated kyphosis and reduced bone mineral density. Elevated levels of blood lysosomal enzymes have also been observed (Kondo et al., 2018).
Y-linked deafness-2 (DFNY2) is characterized by male-limited bilateral progressive sensorineural hearing loss of variable severity, with onset in the third to fifth decades of life (Di Stazio et al., 2019). For a discussion of genetic heterogeneity of Y-linked deafness, see DFNY1 (400043).
Fetal akinesia deformation sequence-4 (FADS4) is an autosomal recessive disorder characterized by decreased fetal movements due to impaired neuromuscular function, resulting in significant congenital contractures and death in utero or soon after birth (summary by Bonnin et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of FADS, see 208150.
Immunodeficiency-60 (IMD60) is an autosomal dominant primary immunologic disorder characterized by inflammatory bowel disease and recurrent sinopulmonary infections. The age at symptom onset is highly variable, ranging from infancy to mid-adulthood. Laboratory studies show dysregulation of both B and T cells, with variably decreased immunoglobulin production, decreased T-regulatory cells, and overall impaired lymphocyte maturation (summary by Afzali et al., 2017).
Spondyloepimetaphyseal dysplasia with joint laxity-3 (SEMDJL3) is characterized by multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age, and poorly ossified carpal and tarsal bones (Girisha et al., 2016). For a discussion of genetic heterogeneity of SEMD with joint laxity, see SEMDJL1 (271640).
Combined oxidative phosphorylation deficiency-39 (COXPD39) is an autosomal recessive multisystem disorder resulting from a defect in mitochondrial energy metabolism. Affected individuals show global developmental delay, sometimes with regression after normal early development, axial hypotonia with limb spasticity or abnormal involuntary movements, and impaired intellectual development with poor speech. More variable features may include hypotonia, seizures, and features of Leigh syndrome (256000) on brain imaging. There are variable deficiencies of the mitochondrial respiratory chain enzyme complexes in patient tissues (summary by Glasgow et al., 2017). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Charcot-Marie-Tooth disease type 2EE (CMT2EE) is an autosomal recessive sensorimotor peripheral axonal neuropathy with onset in the first or second decades of life. The disorder primarily affects the lower limbs and is slowly progressive, sometimes resulting in loss of ambulation, with later onset of upper limb involvement. There is significant distal muscle weakness and atrophy, usually with foot or hand deformities. Skeletal muscle biopsy shows findings of disturbed mitochondrial maintenance. Cognition is unaffected, and chronic liver disease is absent (summary by Baumann et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (118210).
MRT70 is characterized primarily by impaired intellectual development. Mild facial dysmorphism, febrile seizures, and behavioral abnormalities have been reported in some patients (Maddirevula et al., 2018; Perez et al., 2018).
DFNB113 is characterized by postlingual progressive hearing impairment (Booth et al., 2018).
Hypomyelinating leukodystrophy-18 (HLD18) is an autosomal recessive neurologic disorder characterized by onset of global developmental delay usually in early infancy. Affected individuals have very poor psychomotor development, including inability to sit or walk independently in the more severe cases, as well as poor or absent speech, dystonia, and spasticity. A subset of patients may develop seizures. Brain imaging shows hypomyelinating leukodystrophy affecting various brain regions; some patients may also have progressive atrophy of the corpus callosum, thalami, and cerebellum (summary by Pant et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080.
Patients with global developmental delay, progressive ataxia, and elevated glutamine (GDPAG) present in early childhood with delay of both gross and fine motor skills and delayed speech. Ataxia develops by mid- to late childhood, necessitating use of a walker or wheelchair. Plasma glutamine is persistently elevated by a factor of 2.5 despite normal plasma ammonia levels. Residual glutaminase (GLS) activity can be detected in fibroblasts and lymphocytes. One or both alleles of the GLS gene carry an expanded GCA trinucleotide repeat in the 5-prime untranslated region (UTR); the repeat expansion may be found in compound heterozygosity with another GLS mutation. Three patients have been reported (summary by van Kuilenburg et al., 2019).
Atazanavir is an antiretroviral of the protease inhibitor (PI) class that is used to treat human immunodeficiency virus (HIV). Atazanavir is typically given with a pharmacokinetic enhancer such as cobicistat or ritonavir and is prescribed as part of a regimen with other antiretrovirals. Atazanavir inhibits uridine diphosphate glucuronosyltransferase (UGT)1A1 (UGT1A1)- mediated glucuronidation of bilirubin, and causes plasma indirect bilirubin concentrations to increase. Although indirect elevations in bilirubin do not necessarily indicate hepatic injury they may cause jaundice. Specific UGT1A1 mutations that reduce UGT1A1 function, particularly in the homozygous state, may greatly increase the likelihood that a patient prescribed atazanavir will develop hyperbilirubinemia and jaundice, and may increase a patient’s risk of non-adherence. Alternative antiretroviral regiments should be recommended for these patients, unless the reasons to prescribe atazanavir are compelling, or the patient is unconcerned about jaundice. Patients with one decreased function UGT1A1 allele have a much lower likelihood of developing jaundice if prescribed atazanavir and although the likelihood of developing jaundice is low, it is recommended that the possibility be discussed with the patient. Therapeutic recommendations for prescribing atazanavir based on an individual’s UGT1A1 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (https://www.pharmgkb.org/drug/PA10251).
Ondansetron and tropisetron are highly specific and selective members of the 5-HT3 receptor antagonists and are used for the prevention of chemotherapy-induced, radiation-induced and postoperative nausea and vomiting. While tropisetron is extensively metabolized by CYP2D6 to inactive metabolites, ondansetron is metabolized by multiple cytochrome P450 enzymes including CYP3A4, CYP1A2 and CYP2D6, though there is substantial data to support a major role of CYP2D6 in ondansetron metabolism. For both drugs, there is evidence linking the CYP2D6 genotype with phenotypic variability in drug efficacy. CYP2D6 ultrarapid metabolizers may have increased metabolism of the drugs, resulting in decreased drug efficacy. There are suitable alternatives to ondansetron and tropisetron that are not affected by CYP2D6 metabolism. Therapeutic guidelines for ondansetron and tropisetron based on CYP2D6 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (https://www.pharmgkb.org/guideline/PA166161954 and https://www.pharmgkb.org/guideline/PA166161955).
The term 'not provided' is registered in MedGen to support identification of submissions to ClinVar for which no condition was named when assessing the variant. 'not provided' differs from 'not specified', which is used when a variant is asserted to be benign, likely benign, or of uncertain significance for conditions that have not been specified.
Kidney stones (also called renal stones or urinary stones) are small, hard deposits that form in one or both kidneys; the stones are made up of minerals or other compounds found in urine. Kidney stones vary in size, shape, and color. To be cleared from the body (or ""passed""), the stones need to travel through ducts that carry urine from the kidneys to the bladder (ureters) and be excreted. Depending on their size, kidney stones generally take days to weeks to pass out of the body.Kidney stones can cause abdominal or back pain (known as renal colic). Renal colic usually begins sporadically but then becomes constant and can lead to nausea and vomiting. The site of pain can change as the stone moves through the urinary tract. Some small stones pass through the kidney and urinary tract with little discomfort, while larger ones can block the flow of urine and impair kidney function. Kidney stones can also result in blood in the urine (hematuria) or kidney or urinary tract infections. Unusually large stones or stones that are difficult to pass can be medically removed.Although there are many types of kidney stones, four main types are classified by the material they are made of. Up to 75 percent of all kidney stones are composed primarily of calcium. Stones can also be made up of uric acid (a normal waste product), cystine (a protein building block), or struvite (a phosphate mineral). Stones form when there is more of the compound in the urine than can be dissolved. This imbalance can occur when there is an increased amount of the material in the urine, a reduced amount of liquid urine, or a combination of both.People are most likely to develop kidney stones between ages 40 and 60, though the stones can appear at any age. Research shows that 35 to 50 percent of people who have one kidney stone will develop additional stones, usually within 10 years of the first stone.
Arthrochalasia-type EDS is distinguished from other types of EDS by the frequency of congenital hip dislocation and extreme joint laxity with recurrent joint subluxations and minimal skin involvement (Byers et al., 1997; Giunta et al., 2008). For a discussion of genetic heterogeneity of arthrochalasia-type EDS, see 130060.
Monosomy 17q21.31 (17q21.31 microdeletion syndrome) is a chromosomal anomaly characterized by developmental delay, childhood hypotonia, facial dysmorphism, and a friendly/amiable behavior.
Monosomy 5p, also known as Cri du chat syndrome, is a rare autosomal deletion syndrome characterized by a mewing cry (cri du chat) in infancy, multiple congenital anomalies, intellectual disability, microcephaly, and facial dysmorphism.
EEC syndrome is a genetic developmental disorder characterized by ectrodactyly, ectodermal dysplasia, and orofacial clefts (cleft lip/palate).
Transient pseudohypoaldosteronism is a renal tubulopathy characterized by renal tubular resistance to aldosterone, characterized by hyponatremia, metabolic acidosis and hyperkalemia and manifesting as dehydration, secondary to urinary tract malformation and infections in infants.
46,XX ovotesticular disorder of sex development (46,XX ovotesticular DSD) is characterized by histologically confirmed testicular and ovarian tissue in an individual with a 46,XX karyotype.
47, XYY syndrome is a sex chromosome aneuploidy where males receive an additional Y chromosome, and is characterized clinically by tall stature evident from childhood, macrocephaly, facial features (mild hypertelorism, low set ears, a mildly flat malar region), speech delay and an increased risk for social and emotional difficulties, attention deficit hyperactive disorder and autistic spectrum disorder.
Focal facial dermal dysplasia type I (FFDD1), also known as Brauer syndrome, is a focal facial dysplasia (FFDD; see this term) characterized by congenital bitemporal cutis aplasia.
Anterior cutaneous nerve entrapment syndrome (ACNES) is a chronic neuropathic pain syndrome of the abdominal wall caused by entrapment of anterior cutaneous branches of 7 to 12th intercostal nerves along the lateral border of the anterior rectus abdominis fascia causing severe pain and tenderness of the involved dermatome.
Brivaracetam (brand name Briviact) is an antiseizure drug used in the treatment of partial-onset (focal) epilepsy in adults. It is thought to act by binding to a synaptic vesicle glycoprotein, SV2A, and reducing the release of neurotransmitters. Brivaracetam is primarily metabolized by hydrolysis, via amidase enzymes, to an inactive metabolite. To a lesser extent, it is also metabolized by a minor metabolic pathway via CYP2C19-dependent hydroxylation. Individuals who have no CYP2C19 enzyme activity, ""CYP2C19 poor metabolizers"", will have a greater exposure to standard doses of brivaracetam. Because they are less able to metabolize the drug to its inactive form for excretion, they may have an increased risk of adverse effects. The most common adverse effects of brivaracetam therapy include sedation, fatigue, dizziness, and nausea. The recommended starting dosage for brivaracetam monotherapy or adjunctive therapy is 50 mg twice daily (100 mg per day). Based on how the individual responds, the dose of brivaracetam may be decreased to 25 mg twice daily (50 mg per day) or increased up to 100 mg twice daily (200 mg per day). The FDA-approved drug label for brivaracetam states that patients who are CYPC19 poor metabolizers, or are taking medicines that inhibit CYP2C19, may require a dose reduction. Approximately 2% of Caucasians, 4% of African Americans, and 14% of Chinese are CYP2C19 poor metabolizers.
Lacosamide (brand name Vimpat) is an antiseizure drug indicated for adjunctive therapy for partial-onset seizures in pediatric and adult patients with epilepsy. Lacosamide is thought to work by selectively enhancing slow inactivation of voltage-dependent sodium channels. This stabilizes the neuronal membrane and suppresses the repetitive neuronal firing associated with seizures. Several cytochrome P450 (CYP) enzymes are involved in metabolizing active lacosamide to an inactive metabolite, including CYP2C19. Individuals who have no CYP2C19 enzyme activity are known as ""CYP2C19 poor metabolizers"". The FDA-approved drug label for lacosamide cites a small study that found plasma levels of lacosamide were similar in CYP2C19 poor metabolizers (n=4) and normal (extensive) metabolizers (n=8). Therefore, the recommended standard doses of lacosamide may be used for CYP2C19 poor metabolizers.
Pulmonary arterial hypertension is a progressive disorder characterized by abnormally high blood pressure (hypertension) in the pulmonary artery, the blood vessel that carries blood from the heart to the lungs. Pulmonary arterial hypertension is one form of a broader condition known as pulmonary hypertension. Pulmonary hypertension occurs when most of the very small arteries throughout the lungs narrow in diameter, which increases the resistance to blood flow through the lungs. To overcome the increased resistance, blood pressure increases in the pulmonary artery and in the right ventricle of the heart, which is the chamber that pumps blood into the pulmonary artery. Ultimately, the increased blood pressure can damage the right ventricle of the heart.Signs and symptoms of pulmonary arterial hypertension occur when increased blood pressure cannot fully overcome the elevated resistance. As a result, the flow of oxygenated blood from the lungs to the rest of the body is insufficient. Shortness of breath (dyspnea) during exertion and fainting spells are the most common symptoms of pulmonary arterial hypertension. People with this disorder may experience additional symptoms, particularly as the condition worsens. Other symptoms include dizziness, swelling (edema) of the ankles or legs, chest pain, and a rapid heart rate.
Hereditary dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following: heart failure with symptoms of congestion (edema, orthopnea, paroxysmal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion); arrhythmias and/or conduction system disease; thromboembolic disease (from left ventricular mural thrombus) including stroke.
Corneal endothelial dystrophy is characterized by thickening and opacification of the cornea, altered morphology of the endothelium, and secretion of an abnormal collagenous layer at the Descemet membrane. There are both autosomal dominant (CHED1) and autosomal recessive (CHED2; 217700) forms, with the latter being more common and more severe (summary by Vithana et al., 2006).
Ehlers-Danlos syndrome (EDS), classic type is a connective tissue disorder characterized by skin hyperextensibility, abnormal wound healing, and joint hypermobility. It includes two previously designated subtypes (EDS type I and EDS type II) that are now recognized to form a continuum of clinical findings. The skin is smooth, velvety to the touch, and hyperelastic; i.e., it extends easily and snaps back after release (unlike lax, redundant skin, as in cutis laxa). The skin is fragile, as manifested by splitting of the dermis following relatively minor trauma, especially over pressure points (knees, elbows) and areas prone to trauma (shins, forehead, chin). Wound healing is delayed, and stretching of scars after apparently successful primary wound healing is characteristic. Complications of joint hypermobility, such as dislocations of the shoulder, patella, digits, hip, radius, and clavicle, usually resolve spontaneously or are easily managed by the affected individual. Other features include hypotonia with delayed motor development, fatigue and muscle cramps, and easy bruising. Less common findings include mitral and tricuspid valve prolapse, aortic root dilatation, and spontaneous rupture of large arteries.
Crisponi syndrome, the infantile presentation of cold-induced sweating syndrome (CISS), is characterized by dysmorphic features (distinctive facies; lower facial weakness; flexion deformity at the elbows; camptodactyly with fisted hands; misshapen feet and overriding toes); poor suck reflex and severely impaired swallowing; and often temperature spikes with increased risk of seizures and sudden death. During the first decade of life, children with CISS develop profuse sweating of their face, arms, and chest with ambient temperatures below 18º to 22º C and often with other stimuli including apprehension or ingestion of sweets. Affected individuals sweat very little in hot environments and may feel overheated. In the second decade, progressive thoracolumbar kyphoscoliosis requires intervention.
SCN1A-related seizure disorders encompass a spectrum that ranges from simple febrile seizures (FS) and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end. Phenotypes with intractable seizures including, Dravet syndrome, also known as severe myoclonic epilepsy in infancy (SMEI) or polymorphic myoclonic epilepsy in infancy (PMEI), are usually associated with progressive dementia. Less commonly observed phenotypes include myoclonic-astatic epilepsy (MAE or Doose syndrome), Lennox-Gastaut syndrome (LGS), infantile spasms, and vaccine-related encephalopathy and seizures. The phenotype can vary even within the same family.
Charcot-Marie-Tooth hereditary neuropathy type 2 (CMT2) is an axonal (non-demyelinating) peripheral neuropathy characterized by distal muscle weakness and atrophy, mild sensory loss, and normal or near-normal nerve conduction velocities. CMT2 is clinically similar to CMT1, although typically less severe. Peripheral nerves are not enlarged or hypertrophic. The subtypes of CMT2 are similar clinically and distinguished only by molecular genetic findings.
Periventricular heterotopia is a condition in which nerve cells (neurons) do not migrate properly during the early development of the fetal brain, from about the 6th week to the 24th week of pregnancy. Heterotopia means ""out of place."" In normal brain development, neurons form in the periventricular region, located around fluid-filled cavities (ventricles) near the center of the brain. The neurons then migrate outward to form the exterior of the brain (cerebral cortex) in six onion-like layers. In periventricular heterotopia, some neurons fail to migrate to their proper position and form clumps around the ventricles.Periventricular heterotopia usually becomes evident when seizures first appear, often during the teenage years. The nodules around the ventricles are then typically discovered when magnetic resonance imaging (MRI) studies are done. Affected individuals usually have normal intelligence, although some have mild intellectual disability. Difficulty with reading and spelling (dyslexia) has been reported in some people with periventricular heterotopia.Less commonly, individuals with periventricular heterotopia may have more severe brain malformations, small head size (microcephaly), developmental delays, recurrent infections, blood vessel abnormalities, or other problems. Periventricular heterotopia may also occur in association with other conditions such as Ehlers-Danlos syndrome, which results in extremely flexible joints, skin that stretches easily, and fragile blood vessels.
Hereditary hearing loss and deafness may be conductive, sensorineural, or a combination of both; syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems); and prelingual (before language develops) or postlingual (after language develops).
The cardinal features of Gorlin-Chaudhry-Moss syndrome (GCMS) include stocky body build, hypertrichosis, craniosynostosis, conductive hearing loss, normal intelligence, hyperopia, facial dysmorphism, dental anomalies, hypoplastic distal phalanges, umbilical hernia, and genital hypoplasia. The facial dysmorphism consists of brachycephaly, low anterior hairline, coarse hair, midface hypoplasia, short palpebral fissures, microphthalmia, high-arched narrow palate, and posteriorly angulated ears (Rosti et al., 2013).
Hepatocellular carcinoma is the major histologic type of malignant primary liver neoplasm. It is the fifth most common cancer and the third most common cause of death from cancer worldwide. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Hepatoblastomas comprise 1-2% of all malignant neoplasms of childhood, most often occurring in children under 3 years of age. Hepatoblastomas are thought to be derived from undifferentiated hepatocytes (Taniguchi et al., 2002).
Leigh syndrome is a severe neurological disorder that typically arises in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within a couple of years, usually due to respiratory failure. A small number of individuals develop symptoms in adulthood or have symptoms that worsen more slowly. The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia) that leads to eating problems. These problems often result in an inability to grow and gain weight at the expected rate (failure to thrive). Severe muscle and movement problems are common in Leigh syndrome. Affected individuals may develop weak muscle tone (hypotonia), involuntary muscle contractions (dystonia), and problems with movement and balance (ataxia). Loss of sensation and weakness in the limbs (peripheral neuropathy), common in people with Leigh syndrome, may also make movement difficult. Several other features may occur in people with Leigh syndrome. Many affected individuals develop weakness or paralysis of the muscles that move the eyes (ophthalmoparesis); rapid, involuntary eye movements (nystagmus); or degeneration of the nerves that carry information from the eyes to the brain (optic atrophy). Severe breathing problems are common in people with Leigh syndrome, and these problems can worsen until they cause acute respiratory failure. Some affected individuals develop hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. In addition, a substance called lactate can build up in the body, and excessive amounts are often found in the blood, cerebrospinal fluid, or urine of people with Leigh syndrome. The signs and symptoms of Leigh syndrome are caused in part by patches of damaged tissue (lesions) that develop in the brains of people with this condition. A procedure called magnetic resonance imaging (MRI) reveals characteristic lesions in certain regions of the brain and the brainstem (the part of the brain that is connected to the spinal cord). These regions include the basal ganglia, which help control movement; the cerebellum, which controls the ability to balance and coordinates movement; and the brainstem, which controls functions such as swallowing, breathing, hearing, and seeing. The brain lesions are often accompanied by loss of the myelin coating around nerves (demyelination), which reduces the ability of the nerves to activate muscles used for movement or relay sensory information back to the brain.
Loeys-Dietz syndrome (LDS) is characterized by vascular findings (cerebral, thoracic, and abdominal arterial aneurysms and/or dissections) and skeletal manifestations (pectus excavatum or pectus carinatum, scoliosis, joint laxity, arachnodactyly, talipes equinovarus). Approximately 75% of affected individuals have LDS type I with craniofacial manifestations (widely spaced eyes, bifid uvula/cleft palate, craniosynostosis); approximately 25% have LDS type II with systemic manifestations of LDSI but minimal or absent craniofacial features. LDSI and LDSII form a clinical continuum. The natural history of LDS is characterized by aggressive arterial aneurysms (mean age at death 26.1 years) and a high incidence of pregnancy-related complications, including death and uterine rupture.
Feingold syndrome is characterized by digital anomalies (shortening of the 2nd and 5th middle phalanx of the hand, clinodactyly of the little finger, syndactyly of toes 2-3 and/or 4-5, thumb hypoplasia), microcephaly, facial dysmorphism (short palpebral fissures and micrognathia), gastrointestinal atresias (primarily esophageal and/or duodenal), and mild to moderate learning disability.
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss. People with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision. People with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved. Between one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
The short rib-polydactyly syndromes (SRPS) are a group of autosomal recessive lethal skeletal dysplasias characterized by markedly short ribs, short limbs, polydactyly, and multiple anomalies of major organs, including heart, intestines, genitalia, kidney, liver, and pancreas. Five types have been distinguished: SRPS I (Saldino-Noonan type; 263530), SRPS II (Majewski type; see 263520), SRPS III (Verma-Naumoff type), SRPS IV (Beemer-Langer type; 269860), and SRPS V (614091). Significant phenotypic overlap has been reported in these forms (summary by Elcioglu and Hall, 2002).
Autoimmune thrombocytopenic purpura is characterized by a low platelet count, normal bone marrow, and the absence of other causes of thrombocytopenia. It is principally a disorder of increased platelet destruction mediated by autoantibodies to platelet-membrane antigens (George et al., 1994).
Spondyloarthropathy (SpA), one of the commonest chronic rheumatic diseases, includes a spectrum of related disorders comprising the prototype ankylosing spondylitis (AS), a subset of psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthropathy (Miceli-Richard et al., 2004). These phenotypes are difficult to differentiate because they may occur simultaneously or sequentially in the same patient. Studies have suggested that a predominant shared component, including HLA-B27, predisposes to all phenotypic subsets, and that these subsets should be considered as various phenotypic expressions of the same disease (Said-Nahal et al., 2000, Said-Nahal et al., 2001). Braun and Sieper (2007) provided a detailed review of ankylosing spondylitis, including clinical features, pathogenesis, and management. Genetic Heterogeneity of Susceptibility to Spondyloarthropathy Additional susceptibility loci for spondyloarthropathy have been identified on chromosome 9q31-q34 (SPDA2; 183840) and chromosome 2q (SPDA3; 613238).
Kuskokwim syndrome is characterized by joint deformities called contractures that restrict the movement of affected joints. This condition has been found only in a population of native Alaskans known as Yup'ik Eskimos, who live in and around a region of southwest Alaska known as the Kuskokwim River Delta.In Kuskokwim syndrome, contractures most commonly affect the knees, ankles, and elbows, although other joints, particularly of the lower body, can be affected. The contractures are usually present at birth and worsen during childhood. They tend to stabilize after childhood, and they remain throughout life.Some individuals with this condition have other bone abnormalities, most commonly affecting the spine, pelvis, and feet. Affected individuals can develop an inward curve of the lower back (lordosis), a spine that curves to the side (scoliosis), wedge-shaped spinal bones, or an abnormality of the collarbones (clavicles) described as clubbing. Affected individuals are typically shorter than their peers and they may have an abnormally large head (macrocephaly).
Knobloch syndrome is a rare condition characterized by severe vision problems and a skull defect. A characteristic feature of Knobloch syndrome is extreme nearsightedness (high myopia). In addition, several other eye abnormalities are common in people with this condition. Most affected individuals have vitreoretinal degeneration, which is breakdown (degeneration) of two structures in the eye called the vitreous and the retina. The vitreous is the gelatin-like substance that fills the eye, and the retina is the light-sensitive tissue at the back of the eye. Vitreoretinal degeneration often leads to separation of the retina from the back of the eye (retinal detachment). Affected individuals may also have abnormalities in the central area of the retina, called the macula. The macula is responsible for sharp central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. Due to abnormalities in the vitreous, retina, and macula, people with Knobloch syndrome often develop blindness in one or both eyes. Another characteristic feature of Knobloch syndrome is a skull defect called an occipital encephalocele, which is a sac-like protrusion of the brain (encephalocele) through a defect in the bone at the base of the skull (occipital bone). Some affected individuals have been diagnosed with a different skull defect in the occipital region, and it is unclear whether the defect is always a true encephalocele. In other conditions, encephaloceles may be associated with intellectual disability; however, most people with Knobloch syndrome have normal intelligence.
The short rib-polydactyly syndromes (SRPS) are a group of autosomal recessive lethal skeletal dysplasias characterized by markedly short ribs, short limbs, polydactyly, and multiple anomalies of major organs, including heart, intestines, genitalia, kidney, liver, and pancreas. There is phenotypic overlap in various forms of SRPS (summary by Elcioglu and Hall, 2002). Genetic Heterogeneity of Short Rib-Polydactyly Syndrome Five types have been distinguished: SRPS I (Saldino-Noonan type); SRPS II (Majewski type; see 263520), SRPS III (Verma-Naumoff type; 263510), SRPS IV (Beemer-Langer type; 269860), and SRPS V (614091). (Elcioglu and Hall, 2002; Mill et al., 2011).
Mseleni joint disease is a familial degenerative osteoarthropathy affecting several hundred persons in a remote rural region of northern Zululand, South Africa. The condition presents in childhood and progresses relentlessly, leading to severe physical handicap by early adulthood (summary by Agarwal et al., 1997).
The PTEN hamartoma tumor syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and Proteus-like syndrome.
ZAP70-related severe combined immunodeficiency (ZAP70-related SCID) is a cell-mediated immunodeficiency caused by abnormal T-cell receptor (TCR) signaling. Affected children usually present in the first year of life with recurrent bacterial, viral, and opportunistic infections, diarrhea, and failure to thrive. Severe lower respiratory infections and oral moniliasis are common. Affected children usually do not survive past their second year without hematopoietic stem cell transplantation (HSCT).
Primary congenital glaucoma (PCG) is characterized by elevated intraocular pressure (IOP), enlargement of the globe (buphthalmos), edema, and opacification of the cornea with rupture of Descemet's membrane (Haabs striae), thinning of the anterior sclera and iris atrophy, anomalously deep anterior chamber, and structurally normal posterior segment except for progressive glaucomatous optic atrophy. Symptoms include photophobia, blepharospasm, and excessive tearing (hyperlacrimation). Typically, the diagnosis is made in the first year of life. Depending on when treatment is instituted, visual acuity may be reduced and/or visual fields may be restricted. In untreated cases, blindness invariably occurs.
Hypohidrotic ectodermal dysplasia (HED) is characterized by hypotrichosis (sparseness of scalp and body hair), hypohidrosis (reduced ability to sweat), and hypodontia (congenital absence of teeth). The cardinal features of HED become obvious during childhood. The scalp hair is thin, lightly pigmented, and slow-growing. Sweating, although present, is greatly deficient, leading to episodes of hyperthermia until the affected individual or family acquires experience with environmental modifications to control temperature. Only a few abnormally formed teeth erupt, and at a later than average age. Physical growth and psychomotor development are otherwise within normal limits.
The phenotypic spectrum of L1 syndrome includes X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), MASA syndrome (mental retardation, aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs), SPG1 (X-linked complicated hereditary spastic paraplegia type 1), and X-linked complicated corpus callosum agenesis. Males with HSAS are born with severe hydrocephalus, adducted thumbs, and spasticity; intellectual disability is severe. In less severely affected males, hydrocephalus may be subclinically present and documented only because of developmental delay; intellectual disability ranges from mild (IQ: 50-70) to moderate (IQ: 30-50).
Congenital contractural arachnodactyly (CCA) is characterized by a Marfan-like appearance (tall, slender habitus in which arm span exceeds height) and long, slender fingers and toes (arachnodactyly). Most affected individuals have ""crumpled"" ears that present as a folded upper helix of the external ear and most have contractures of major joints (knees and ankles) at birth. The proximal interphalangeal joints also have flexion contractures (i.e., camptodactyly), as do the toes. Hip contractures, adducted thumbs, and club foot may occur. The majority of affected individuals have muscular hypoplasia. Contractures usually improve with time. Kyphosis/scoliosis is present in about half of all affected individuals. It begins as early as infancy, is progressive, and causes the greatest morbidity in CCA. Dilatation of the aorta is occasionally present. Infants have been observed with a severe/lethal form characterized by multiple cardiovascular and gastrointestinal anomalies in addition to the typical skeletal findings.
Roberts syndrome (RBS) is characterized by prenatal growth retardation (ranging from mild to severe) and limb malformations (including bilateral symmetric tetraphocomelia or hypomelia caused by mesomelic shortening). Upper limbs are more severely affected than lower limbs. Other limb malformations include oligodactyly with thumb aplasia or hypoplasia, syndactyly, clinodactyly, and elbow and knee flexion contractures. Craniofacial abnormalities include cleft lip and/or cleft palate, premaxillary protrusion, micrognathia, microbrachycephaly, malar hypoplasia, downslanting palpebral fissures, ocular hypertelorism, exophthalmos resulting from shallow orbits, corneal clouding, hypoplastic nasal alae, beaked nose, and ear malformations. Intellectual disability is reported in the majority of affected individuals. Mortality is high among severely affected pregnancies and newborns. Mildly affected individuals may survive to adulthood.
The WAS-related disorders, which include Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked congenital neutropenia (XLN), are a spectrum of disorders of hematopoietic cells, with predominant defects of platelets and lymphocytes caused by mutations in WAS. WAS-related disorders usually present in infancy. Affected males have thrombocytopenia with intermittent mucosal bleeding, bloody diarrhea, and intermittent or chronic petechiae and purpura; eczema; and recurrent bacterial and viral infections, particularly recurrent ear infections. At least 40% of those who survive the early complications develop one or more autoimmune conditions including hemolytic anemia, immune thrombocytopenic purpura (ITP), immune-mediated neutropenia, arthritis, vasculitis of small and large vessels, and immune-mediated damage to the kidneys and liver. Individuals with a WAS-related disorder, particularly those who have been exposed to Epstein-Barr virus (EBV), have an increased risk of developing lymphomas, which often occur in unusual, extranodal locations such as the brain, lung, or gastrointestinal tract. Males with XLT have thrombocytopenia with small platelets; other complications of Wiskott-Aldrich syndrome, including eczema and immune dysfunction, are mild or absent.
The dystrophinopathies include a spectrum of muscle disease caused by mutations in the DMD gene, which encodes the protein dystrophin. The mild end of the spectrum includes the phenotypes of asymptomatic increase in serum concentration of creatine phosphokinase (CK) and muscle cramps with myoglobinuria and isolated quadriceps myopathy. The severe end of the spectrum includes progressive muscle diseases that are classified as Duchenne/Becker muscular dystrophy when skeletal muscle is primarily affected and as DMD-associated dilated cardiomyopathy (DCM) when the heart is primarily affected. Duchenne muscular dystrophy (DMD) usually presents in early childhood with delayed milestones, including delays in sitting and standing independently. Proximal weakness causes a waddling gait and difficulty climbing. DMD is rapidly progressive, with affected children being wheelchair bound by age 12 years. Cardiomyopathy occurs in all affected individuals after age 18 years. Few survive beyond the third decade, with respiratory complications and cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness; individuals remain ambulatory into their 20s. Despite the milder skeletal muscle involvement, heart failure from DCM is a common cause of morbidity and the most common cause of death. Mean age of death is in the mid-40s. DMD-associated DCM is characterized by left ventricular dilation and congestive heart failure. Female carriers of DMD mutations are at increased risk for DCM.
46,XY disorder of sex development (46,XY DSD) is characterized by a 46,XY karyotype, ambiguous genitalia with mild to severe penoscrotal hypospadias with or without chordee, dysgenetic testes, reduced to no sperm production, and müllerian structures that range from absent to presence of a fully developed uterus and fallopian tubes. 46,XY complete gonadal dysgenesis (46,XY CGD) is characterized by a 46,XY karyotype, normal female external genitalia, completely undeveloped (”streak”) gonads, no sperm production, and presence of normal müllerian structures.
Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder of long-chain fatty-acid oxidation. The three clinical presentations are: lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form that is usually mild and can manifest from infancy to adulthood. While the former two are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death, the latter is characterized by exercise-induced muscle pain and weakness, sometimes associated with myoglobinuria. The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and is the most frequent cause of hereditary myoglobinuria. Males are more likely to be affected than females.
Primary familial brain calcification (PFBC) is a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas visualized on neuroimaging. Most affected individuals are in good health during childhood and young adulthood and typically present in the fourth to fifth decade with gradually progressive neuropsychiatric and movement disorders. The main manifestations include clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Migraine is frequent and seizures of various types may also occur. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia.
Warfarin is a widely prescribed anticoagulant for the prevention of thromboembolic diseases for subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement (Yuan et al., 2005). The dose requirement is highly variable, both interindividually and interethnically. Variation in the VKORC1 gene is believed to be the most important individual predictor of warfarin dose, accounting for about 30% of the variance observed in dosing (Ross et al., 2010).
The diagnostic criteria for short rib-polydactyly type II (Majewski syndrome) include short and narrow thorax, horizontally oriented ribs, short tubular bones with smooth ends, ovoid tibiae that are shorter than the fibulae or tibial agenesis, and pre- and/or postaxial polysyndactyly (summary by El Hokayem et al., 2012). Mutation in the DYNC2H1 gene has also been implicated in SRPS III (263510). Additionally, there is evidence that short rib-polydactyly type II can be caused by digenic biallelic mutation in the NEK1 (604588) and DYNC2H1 genes.
BPIDS is characterized by blepharophimosis, ptosis, mild upslanting of the palpebral fissures, epicanthus, ectodermal anomalies, developmental delay, and severe intellectual disability with absent speech. Proportionate growth retardation with a small head circumference/microcephaly, congenital malformations, muscular hypotonia, anomalies on brain imaging with hypoplasia of the corpus callosum, and low cholesterol levels are variably present (Basel-Vanagaite et al., 2012).
The thiopurines include azathioprine (a pro-drug for mercaptopurine), mercaptopurine and thioguanine. They are used to treat a variety of immunological disorders such as rheumatoid arthritis, non- Hodgkin lymphoma and ulcerative colitis. Both mercaptopurine and thioguanine can exert cytotoxic effects through the formation of thioguanine nucleotides (TGNs), active metabolites that incorporate into DNA. Mercaptopurine and thioguanine are directly inactivated by thiopurine S-methyltransferase (TPMT). Individuals with two nonfunctional TPMT alleles are at 100% risk of potentially fatal myelosuppression, due to an increased buildup of toxic TGNs. Alternative agents or a drastically reduced dose are recommended for patients with this genotype. Patients heterozygous for a nonfunctional TPMT allele are at increased risk of myelosuppression, and reduced dosing is recommended for these individuals. These dosing guidelines have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website (http://www.pharmgkb.org/gene/PA356)
Culler-Jones syndrome (CJS) is an autosomal dominant disorder characterized by hypopituitarism, mainly growth hormone deficiency, and/or postaxial polydactyly. The phenotype is highly variable, and some patients may have midline facial defects and developmental delay. The disorder shows incomplete penetrance and variable expressivity (summary by Franca et al., 2010).
DECR deficiency is a very rare autosomal recessive inborn error of metabolism resulting in mitochondrial dysfunction. Affected individuals have a severe encephalopathy with neurologic and metabolic dysfunction beginning in early infancy. Laboratory studies show decreased activity of the mitochondrial NADP(H)-dependent enzymes DECR1 (222745) and AASS (605113), resulting in increased C10:2-carnitine levels and hyperlysinemia (summary by Houten et al., 2014).
Usher syndrome type II is characterized by congenital (i.e., prelingual) bilateral sensorineural hearing loss that is mild to moderate in the low frequencies and severe to profound in the higher frequencies, intact vestibular responses, and retinitis pigmentosa (RP). RP is progressive, bilateral, symmetric retinal degeneration that begins with night blindness and constricted visual fields (tunnel vision) and eventually includes decreased central visual acuity; the rate and degree of vision loss vary within and among families.
CAV3-related distal myopathy is one form of distal myopathy, a group of disorders characterized by weakness and loss of function affecting the muscles farthest from the center of the body (distal muscles), such as those of the hands and feet. People with CAV3-related distal myopathy experience wasting (atrophy) and weakness of the small muscles in the hands and feet that generally become noticeable in adulthood. A bump or other sudden impact on the muscles, especially those in the forearms, may cause them to exhibit repetitive tensing (percussion-induced rapid contraction). The rapid contractions can continue for up to 30 seconds and may be painful. Overgrowth (hypertrophy) of the calf muscles can also occur in CAV3-related distal myopathy. The muscles closer to the center of the body (proximal muscles) such as the thighs and upper arms are normal in this condition.
Multiple self-healing palmoplantar carcinoma (MSPC) primarily affects epithelial tissues devoid of hair follicles, such as the palmoplantar skin and conjunctival epithelium. Lesions appear in the first 3 decades of life and arise at points of pressure and friction. The tumors range in size from 5 to 50 mm and have a tendency to transform into squamous cell carcinoma with metastases (Mamai et al., 2015).
The Borck type of X-linked syndromic mental retardation is an X-linked recessive neurodevelopmental disorder characterized by global developmental delay, short stature, microcephaly, and poor or absent speech. Patients have dysmorphic facial features, growth hormone deficiency, hypogonadism, and spasticity resulting in difficulty walking or inability to walk. Brain imaging shows thin corpus callosum and reduced white matter volume (summary by Borck et al., 2012).